{ "date": "2025-12-18", "relationships": [ { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects secretion/activity; high glucose alters expression.", "mechanism": "Persistent upregulation impairs keratinocyte migration and delays wound healing.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). 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A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "causal", "source_pmcid": "PMC10002069" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation modulates anti-angiogenic activity.", "mechanism": "Increased TSP-1 inhibits angiogenesis, delaying wound healing.", "protein": "Thrombospondin-1 (TSP-1)", "protein_enriched": { "function": "Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:15014436, PubMed:18285447, PubMed:2430973, PubMed:6489349). Multifunctional, involved in inflammation, angiogen", "gene_name": "THBS1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G37881RL", "G52527GH", "G56784JY", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G06110VR", "G06356OH", "G07755XJ", "G08290VR", "G08918WF", "G09197ZW", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G12313PD", "G14260UH", "G14669DU", "G14994KB", "G15664MX", "G16175ZV", "G18647XP", "G20210JR", "G20425TQ", "G22140GZ", "G22310AV", "G23432EQ", "G23453IV", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31852PQ", "G31916IQ", "G31936TA", "G32332VU", "G33609NS", "G34989PA", "G35029YA", "G37399XV", "G37412TK", "G37509XX", "G37868ZX", "G39446WN", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46687AB", "G46691LC", "G46902YN", "G47644PP", "G48414YA", "G48584BU", "G49906RN", "G49955PK", "G50045TK", "G50757KG", "G51640FO", "G54612UD", "G55383ZG", "G57317CE", "G57776ZU", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G61256FT", "G62765YT", "G64527OM", "G65092SV", "G65184UU", "G66621EA", "G66766XF", "G70101JE", "G70418MS", "G70441OD", "G70619PT", "G72291OX", "G72398FA", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G75983OB", "G76295SF", "G78790NZ", "G79568CQ", "G80223IX", "G80920RR", "G81263BG", "G81295CK", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84820NF", "G85554PZ", "G86182NS", "G87399DK", "G87661QW", "G89098OM", "G90659AW", "G90734RJ", "G91636VS", "G92050GC", "G92406TI", "G95046LV", "G95865ZB", "G49108TO", "G00273SJ", "G02528FI", "G07246CJ", "G08110WX", "G10846ZT", "G11629QQ", "G14972EH", "G17208MA", "G20706XG", "G28622IK", "G37818NZ", "G40834TG", "G43669FQ", "G43734MM", "G57776ZS", "G59324HL", "G60834IK", "G64409MC", "G65000LJ", "G70223PD", "G70232NH", "G72667IM", "G73430PD", "G77547TA", "G79666IR", "G80479JV", "G81198YO", "G84225JN", "G85282JO", "G86880BF", "G87123QX", "G90382BL", "G90575OW", "G92135MA", "G92551JA", "G93718GY", "G95977AE", "G98611JV", "G99966GV", "G57321FI", "G02030ZB", "G05724UK", "G08146BT", "G10256JP", "G11870QZ", "G12341GU", "G13910DJ", "G20528HD", "G22625SJ", "G23294PN", "G29299MO", "G29880MM", "G33584ML", "G39188ZX", "G39619TI", "G47012YE", "G47950XN", "G49874UX", "G60177UT", "G63041LO", "G63381RX", "G70375MX", "G72797UR", "G74430RZ", "G80075MS", "G85269DF", "G87051GH", "G95177YH", "G96577RX", "G61491DK", "G06038KF", "G42494UJ", "G96881BQ", "G42518JM", "G81399MY", "G29068FM", "G70323CJ" ], "uniprot_id": "P07996" }, "relationship_type": "causal", "source_pmcid": "PMC10002069" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Reduced HBD-2 impairs antimicrobial defense and keratinocyte proliferation.", "protein": "Human beta-defensin 2 (HBD-2)", "protein_enriched": { "function": "Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria (PubMed:10837369, PubMed:9202117). Antimicrobial activit", "gene_name": "DEFB4A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15263" }, "relationship_type": "protective", "source_pmcid": "PMC10002069" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Reduced HBD-3 impairs antimicrobial defense and wound healing.", "protein": "Human beta-defensin 3 (HBD-3)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5UQV5" }, "relationship_type": "protective", "source_pmcid": "PMC10002069" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects peptide processing and activity.", "mechanism": "Decreased LL-37 reduces antimicrobial protection in keratinocytes.", "protein": "Cathelicidin (LL-37)", "protein_enriched": { "function": "Antimicrobial protein that is an integral component of the innate immune system (PubMed:14978112, PubMed:16637646, PubMed:18818205, PubMed:22879591, PubMed:9736536). Binds to bacterial lipopolysacchar", "gene_name": "CAMP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P49913" }, "relationship_type": "protective", "source_pmcid": "PMC10002069" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Reduced MMP-2 activity impairs keratinocyte migration and ECM remodeling.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "causal", "source_pmcid": "PMC10002069" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects integrin and MMP function.", "mechanism": "Reduced MMP-1 and \u03b12\u03b21 integrin expression impairs migration on collagen.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "causal", "source_pmcid": "PMC10002069" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-GlcNAc modification of IRS promotes insulin resistance.", "mechanism": "Impaired IRS phosphorylation and O-GlcNAc modification contribute to insulin resistance and T2DM.", "protein": "IRS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation required for IR function; defects impact signaling.", "mechanism": "Defective IR signaling leads to impaired glucose uptake and insulin resistance.", "protein": "IR", "relationship_type": "causal", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Potential glycosylation affects receptor localization and function.", "mechanism": "ER\u03b1 signaling improves cardiovascular health and insulin sensitivity.", "protein": "ER\u03b1", "relationship_type": "protective", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects GLUT4 trafficking and function.", "mechanism": "GLUT4 translocation is regulated by insulin and estrogen signaling, affecting glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10031253" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Indirect; Sirt1 modulates glycoprotein signaling.", "mechanism": "Sirt1 deacetylates ER\u03b1 and IRS2, regulating autophagy and adiposity.", "protein": "Sirt1", "relationship_type": "protective", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "PI3K interacts with glycoprotein receptors.", "mechanism": "PI3K signaling regulates hepatic glucose and lipid metabolism; dysregulation leads to NAFLD.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Muscle Atrophy", "glycan_involvement": "Akt activity modulated by upstream glycoproteins.", "mechanism": "Reduced Akt phosphorylation increases FoxO nuclear translocation, promoting muscle protein degradation.", "protein": "Akt", "protein_enriched": { "function": "AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, gro", "gene_name": "Akt1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47196" }, "relationship_type": "causal", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Regulated by glycoprotein signaling cascades.", "mechanism": "FoxO1 upregulates gluconeogenic genes when insulin signaling is impaired.", "protein": "FoxO1", "protein_enriched": { "function": "Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:1589067", "gene_name": "FOXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q12778" }, "relationship_type": "causal", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects receptor function and drug response.", "mechanism": "GLP1 receptor agonists restore insulin secretion and improve glycemic control.", "protein": "GLP1 Receptor", "protein_enriched": { "function": "G-protein coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712). Ligand binding trig", "gene_name": "GLP1R", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P43220" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10031253" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation may affect receptor localization in mitochondria.", "mechanism": "ER\u03b2 signaling protects against neurodegeneration.", "protein": "ER\u03b2", "relationship_type": "protective", "source_pmcid": "PMC10031253" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "O-GlcNAcylation of nuclear and cytoplasmic proteins modulates metabolic pathways.", "mechanism": "OGT acts as a nutrient sensor; high sugar diet increases OGT activity, impacting gene expression and metabolic adaptation.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10036121" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation of Polycomb proteins and histones alters gene repression.", "mechanism": "OGT-mediated O-GlcNAcylation regulates chromatin and developmental gene networks exploited in cancer.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10036121" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "O-GlcNAcylation of synaptic and nuclear proteins affects neural function.", "mechanism": "OGT regulates neural plasticity and synaptic function; dysregulation linked to neurodegenerative processes.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10036121" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "OGT O-GlcNAcylates PRC2.1 components, affecting repression.", "mechanism": "PRC2.1 represses developmental genes; OGT-mediated modulation may contribute to oncogenic reprogramming.", "protein": "Polycomb Repressive Complex 2.1 (PRC2.1)", "relationship_type": "causal", "source_pmcid": "PMC10036121" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "O-GlcNAcylation of neural proteins modulates excitability.", "mechanism": "OGT activity and O-GlcNAcylation linked to neural excitability and plasticity.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10036121" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "O-GlcNAcylation of chromatin and synaptic proteins.", "mechanism": "Altered OGT activity may affect neural gene expression and plasticity.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10036121" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "O-GlcNAcylation of synaptic proteins.", "mechanism": "OGT regulates synaptic function and plasticity; 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Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC10140882" }, { "confidence": "high", "disease": "Hypogammaglobulinemia", "glycan_involvement": "Abnormal N- and O-glycosylation of immunoglobulins.", "mechanism": "Defective glycosylation impairs immunoglobulin production and function.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC10140882" }, { "confidence": "high", "disease": "Liver Dysfunction/Failure", "glycan_involvement": "Impaired glycosylation of hepatic proteins.", "mechanism": "ATP6AP1 mutations lead to hepatopathy via glycosylation defects.", "protein": "ATP6AP1", "protein_enriched": { "function": "Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V1H", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UI12" }, "relationship_type": "causal", "source_pmcid": "PMC10140882" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Defective glycosylation of bile-related proteins.", "mechanism": "Glycosylation defects disrupt bile secretion and liver function.", "protein": "ATP6AP1", "protein_enriched": { "function": "Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V1H", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UI12" }, "relationship_type": "causal", "source_pmcid": "PMC10140882" }, { "confidence": "medium", "disease": "Cutis Laxa", "glycan_involvement": "Abnormal glycosylation of skin structural proteins.", "mechanism": "Glycosylation defects affect extracellular matrix proteins.", "protein": "ATP6AP1", "protein_enriched": { "function": "Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V1H", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UI12" }, "relationship_type": "causal", "source_pmcid": "PMC10140882" }, { "confidence": "medium", "disease": "Neurological Symptoms (Seizures, Intellectual Disability)", "glycan_involvement": "Impaired glycosylation of neural glycoproteins.", "mechanism": "Defective glycosylation impacts neuronal protein function.", "protein": "ATP6AP1", "protein_enriched": { "function": "Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V1H", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UI12" }, "relationship_type": "causal", "source_pmcid": "PMC10140882" }, { "confidence": "high", "disease": "TNBC", "glycan_involvement": "O-GlcNAcylation of multiple substrates, especially TET1.", "mechanism": "OGT is overexpressed in TNBC tumors and cell lines, driving O-GlcNAcylation of key proteins that promote tumorigenesis.", "protein": "OGT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10210312" }, { "confidence": "high", "disease": "TNBC", "glycan_involvement": "O-GlcNAcylation at serine/threonine residues enhances TET1 activity.", "mechanism": "TET1 is O-GlcNAcylated by OGT, activating its function in a pathway that expands cancer stem-like cells.", "protein": "TET1", "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Increased O-GlcNAcylation due to hyperglycemia.", "mechanism": "Diet-induced obesity in mice leads to elevated OGT expression and O-GlcNAcylation in TNBC tumors.", "protein": "OGT", "relationship_type": "biomarker", "source_pmcid": "PMC10210312" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glucose flux increases UDP-GlcNAc substrate for OGT.", "mechanism": "Hyperglycemia associated with diabetes increases OGT activity and O-GlcNAcylation, linking metabolic disease to TNBC risk.", "protein": "OGT", "relationship_type": "biomarker", "source_pmcid": "PMC10210312" }, { "confidence": "high", "disease": "Cancer stem cell expansion", "glycan_involvement": "O-GlcNAc modification is required for full TET1 activity.", "mechanism": "O-GlcNAcylation of TET1 by OGT activates a transcriptional pathway (TET1-TARDBP-SRSF2-MBD2_v2) leading to CSC expansion.", "protein": "TET1", "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "medium", "disease": "TNBC", "glycan_involvement": "Indirect; regulated by O-GlcNAcylated TET1.", "mechanism": "TARDBP is a downstream target of TET1 and is necessary for OGT expression and CSC pathway activation.", "protein": "TARDBP", "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "medium", "disease": "TNBC", "glycan_involvement": "Indirect; part of OGT/TET1-driven pathway.", "mechanism": "MBD2_v2 is downstream in the TET1 pathway and is required for CSC maintenance; its overexpression rescues CSCs from OGT inhibition.", "protein": "MBD2_v2", "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "high", "disease": "Cancer stem cell expansion", "glycan_involvement": "O-GlcNAcylation of pathway proteins.", "mechanism": "OGT activity is necessary for maintenance of CSCs in TNBC; inhibition reduces CSC population.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "medium", "disease": "TNBC", "glycan_involvement": "Indirect; pathway member.", "mechanism": "SRSF2 is part of the TET1-driven pathway for CSC expansion, regulated downstream of OGT/TET1.", "protein": "SRSF2", "protein_enriched": { "function": "Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites", "gene_name": "SRSF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01130" }, "relationship_type": "causal", "source_pmcid": "PMC10210312" }, { "confidence": "medium", "disease": "TNBC", "glycan_involvement": "Removes O-GlcNAc; low levels favor glycosylation.", "mechanism": "OGA expression is lower in TNBC compared to other breast cancer subtypes, contributing to higher O-GlcNAcylation.", "protein": "OGA", "protein_enriched": { "function": "Cleaves GlcNAc but not GalNAc from O-glycosylated proteins (PubMed:11148210, PubMed:11788610, PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839, PubMed:37962578). Deglycosylates a lar", "gene_name": "OGA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "O60502" }, "relationship_type": "biomarker", "source_pmcid": "PMC10210312" }, { "confidence": "high", "disease": "Muscle-eye-brain disease (MEB)", "glycan_involvement": "Defective O-mannosyl glycan synthesis on alpha-dystroglycan", "mechanism": "Loss-of-function splice-site variant leads to defective glycosylation of alpha-dystroglycan, causing MEB.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "high", "disease": "Dystroglycanopathy (DGP)", "glycan_involvement": "Impaired O-mannosyl glycosylation", "mechanism": "Mutations in POMGNT1 disrupt O-glycosylation of alpha-dystroglycan, resulting in DGP spectrum disorders.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "high", "disease": "Congenital muscular dystrophy (CMD)", "glycan_involvement": "Defective O-glycosylation of alpha-dystroglycan", "mechanism": "Pathogenic variants in POMGNT1 cause CMD with intellectual disability via glycosylation defects.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Type II lissencephaly", "glycan_involvement": "Impaired O-mannosyl glycosylation", "mechanism": "Homozygous c.636C>T variant in POMGNT1 reported in fetal type II lissencephaly.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Defective O-mannosyl glycosylation", "mechanism": "UPD for POMT2 leads to LGMD via defective O-mannosylation.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Dystroglycanopathy (DGP)", "glycan_involvement": "Defective O-glycosylation", "mechanism": "UPD for B3GALNT2 causes milder DGP phenotype via glycosylation defect.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "high", "disease": "Dystroglycanopathy (DGP)", "glycan_involvement": "O-mannosyl glycan deficiency", "mechanism": "Hypoglycosylated alpha-dystroglycan is a hallmark of DGP.", "protein": "alpha-dystroglycan", "protein_enriched": { "function": "Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immu", "gene_name": "LAT", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O43561" }, "relationship_type": "biomarker", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Defective O-mannosyl glycosylation", "mechanism": "Variants in POMGNT1 can cause severe FCMD via glycosylation defects.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective O-mannosyl glycosylation", "mechanism": "POMGNT1 mutations can cause WWS, a severe DGP phenotype.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Partial O-mannosyl glycosylation deficiency", "mechanism": "Milder POMGNT1 mutations can cause LGMD via partial glycosylation defects.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10277930" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "O-glycosylation is essential for ligand binding; loss causes disease.", "mechanism": "Defective glycosylation reduces dystroglycan's affinity for ECM ligands, leading to muscle fragility and congenital muscular dystrophy.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Indirect; dystrophin interacts with glycosylated dystroglycan.", "mechanism": "Loss-of-function mutations in dystrophin disrupt cytoskeleton-ECM linkage, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "high", "disease": "Basement Membrane Assembly Defects", "glycan_involvement": "O-glycosylation required for ECM protein binding and BM assembly.", "mechanism": "Dystroglycan anchors ECM proteins for basement membrane assembly; loss impairs BM formation in muscle, retina, and brain.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "high", "disease": "Retinal and Brain Developmental Disorders", "glycan_involvement": "O-glycosylation required for function.", "mechanism": "Dystroglycan deficiency disrupts BM formation in retina and brain, leading to developmental defects.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "high", "disease": "Becker Muscular Dystrophy (BMD)", "glycan_involvement": "Indirect via dystroglycan interaction.", "mechanism": "Partial loss or mutation of dystrophin domains leads to milder muscle disease.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "medium", "disease": "Ischemia during Exercise", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Alpha-syntrophin recruits nNOS to sarcolemma via dystrophin, promoting vasodilation and preventing ischemia.", "protein": "Alpha-syntrophin", "protein_enriched": { "function": "Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the extracellular matrix v", "gene_name": "SNTA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13424" }, "relationship_type": "protective", "source_pmcid": "PMC10293626" }, { "confidence": "medium", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "Indirect via DAPC integrity.", "mechanism": "Dystrophin loss leads to hyperactivation of stretch-activated channels (TRPC6), contributing to cardiac dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "medium", "disease": "Stem Cell Niche Expansion", "glycan_involvement": "O-glycosylation mediates ECM interactions.", "mechanism": "Dystroglycan and perlecan regulate BM niche size in Drosophila spermatogenesis.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "medium", "disease": "Satellite Cell Division Defects", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Dystrophin interacts with MARK2/Par-1b to regulate asymmetric division of muscle stem cells.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "medium", "disease": "Neuromuscular Junction Defects", "glycan_involvement": "O-glycosylation of dystroglycan is critical for ECM ligand binding.", "mechanism": "DAPC required for proper neuromuscular junction assembly.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10293626" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-GlcNAcylation regulates SGLT1 expression.", "mechanism": "Suppression of O-GlcNAcylation reduces SGLT1 expression and glucose absorption.", "protein": "SGLT1", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a tr", "gene_name": "SLC5A1", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G49108TO" ], "uniprot_id": "P13866" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10327358" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-GlcNAcylation of GLUT1 affects its function.", "mechanism": "O-GlcNAcylation and acetylation modulate GLUT1 activity and glucose uptake.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation status affects GLUT2 stability and function.", "mechanism": "ER stress-mediated ubiquitination and glycosylation of GLUT2 reduce glucose uptake, worsening hyperglycemia.", "protein": "GLUT2", "protein_enriched": { "function": "Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "causal", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates GLUT4 trafficking.", "mechanism": "Glycosylation and ubiquitination regulate GLUT4 translocation and glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10327358" }, { "confidence": "high", "disease": "Tumor/Cancer", "glycan_involvement": "O-GlcNAcylation at S529 inhibits PFK1.", "mechanism": "O-GlcNAcylation of PFK1 inhibits its activity, redirecting glucose flux to the pentose phosphate pathway, supporting tumor growth.", "protein": "PFK1", "protein_enriched": { "function": "Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis", "gene_name": "PFKM", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08237" }, "relationship_type": "causal", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Tumor/Cancer", "glycan_involvement": "O-GlcNAcylation modulates PKM2 stability and function.", "mechanism": "O-GlcNAcylation and other PTMs regulate PKM2 expression and activity, promoting the Warburg effect.", "protein": "PKM2", "protein_enriched": { "function": "Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:2084", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618" }, "relationship_type": "causal", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects CD36 localization and function.", "mechanism": "Glycosylation and palmitoylation of CD36 regulate fatty acid uptake and lipid accumulation, contributing to atherosclerosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects enzyme stability.", "mechanism": "N-glycosylation and ubiquitination regulate HMG-CoA reductase degradation, influencing cholesterol biosynthesis.", "protein": "HMG-CoA reductase", "protein_enriched": { "function": "Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in c", "gene_name": "HMGCR", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G46503DX", "G48584BU", "G62765YT", "G64527OM", "G70101JE", "G49108TO", "G80920RR" ], "uniprot_id": "P04035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Non-alcoholic Fatty Liver Disease", "glycan_involvement": "Glycosylation modulates ASBT stability and function.", "mechanism": "Glycosylation and phosphorylation regulate ASBT membrane expression and bile acid reabsorption.", "protein": "ASBT (SLC10A2)", "protein_enriched": { "function": "Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:7592981, PubMed:9458785, PubMed:9856990). Transports various bile acids, unconjug", "gene_name": "SLC10A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q12908" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10327358" }, { "confidence": "medium", "disease": "Maternal Metabolic Disorders", "glycan_involvement": "Aberrant glycosylation disrupts placental protein function.", "mechanism": "ER stress-mediated perturbation of placental glycoprotein glycosylation leads to maladaptation of maternal hepatic glucose metabolism.", "protein": "Placental glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10327358" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation Type Ia (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation of glycoproteins due to impaired mannose metabolism.", "mechanism": "PMM2 deficiency impairs N-glycosylation, leading to multisystem disease.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "high", "disease": "Developmental Delay", "glycan_involvement": "Defective glycosylation of neural glycoproteins.", "mechanism": "Impaired glycosylation affects CNS development.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "high", "disease": "Cognitive Impairment", "glycan_involvement": "Altered glycoprotein processing in the brain.", "mechanism": "Abnormal glycosylation disrupts neuronal function.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "medium", "disease": "Generalized Hypotonia", "glycan_involvement": "Impaired glycosylation of muscle/nerve glycoproteins.", "mechanism": "Glycosylation defects impact muscle and nerve function.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "medium", "disease": "Paraplegia", "glycan_involvement": "Defective glycoproteins in CNS and peripheral nerves.", "mechanism": "Multisystem glycosylation defects can affect motor pathways.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "high", "disease": "Coagulation Disorders", "glycan_involvement": "Abnormal glycosylation of plasma glycoproteins involved in coagulation.", "mechanism": "Glycosylation defects alter coagulation factor function.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC10348842" }, { "confidence": "medium", "disease": "Mitochondrial Encephalopathy, Lactic Acidosis, and Strokelike Episodes (MELAS)", "glycan_involvement": "No direct glycosylation involvement in MELAS; distinction is clinical.", "mechanism": "PMM2-CDG may be misdiagnosed as MELAS due to overlapping neurological features.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC10348842" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Laminin is a glycoprotein; glycosylation required for function.", "mechanism": "Global deletion leads to severe muscular dystrophy and early death.", "protein": "Laminin-211 (\u03b12\u03b21\u03b31)", "relationship_type": "causal", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "BBB disruption", "glycan_involvement": "Glycosylation essential for laminin structure and signaling.", "mechanism": "Astrocyte-specific or global deletion impairs BBB integrity, reduces tight junctions, and pericyte coverage.", "protein": "Laminin-211 (\u03b12\u03b21\u03b31)", "relationship_type": "causal", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "BBB disruption", "glycan_involvement": "Glycosylation required for laminin assembly and function.", "mechanism": "Deletion disrupts vascular development and integrity; compensatory upregulation of laminin-511 can enhance BBB.", "protein": "Laminin-411 (\u03b14\u03b21\u03b31)", "relationship_type": "causal/protective", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "Multiple sclerosis (EAE model)", "glycan_involvement": "Glycosylation mediates laminin-receptor interactions.", "mechanism": "Upregulation inhibits leukocyte infiltration and enhances BBB integrity.", "protein": "Laminin-511 (\u03b15\u03b21\u03b31)", "relationship_type": "protective", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "BBB disruption", "glycan_involvement": "Integrin glycosylation modulates ligand binding.", "mechanism": "Partial deletion increases BBB leak; required for vascular BM integrity.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "causal/protective", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "Multiple sclerosis (EAE model)", "glycan_involvement": "Glycosylation affects integrin-laminin binding.", "mechanism": "Induced during neuroinflammation; deletion worsens BBB breakdown and disease severity.", "protein": "Integrin \u03b16\u03b24", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10358660" }, { "confidence": "medium", "disease": "BBB disruption", "glycan_involvement": "Highly glycosylated; glycan chains required for laminin binding.", "mechanism": "Astrocyte-specific deletion alters endfeet architecture but does not affect BBB under normal conditions.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "biomarker", "source_pmcid": "PMC10358660" }, { "confidence": "medium", "disease": "Multiple sclerosis (EAE model)", "glycan_involvement": "Glycosylation required for inhibitory function.", "mechanism": "Expression in parenchymal BM inhibits leukocyte infiltration.", "protein": "Laminin-111 (\u03b11\u03b21\u03b31)", "relationship_type": "protective", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "Intraventricular hemorrhage (premature neonates)", "glycan_involvement": "Glycosylation essential for laminin stability.", "mechanism": "Low laminin levels correlate with fragile vessels; upregulation (e.g., by indomethacin) protects against hemorrhage.", "protein": "Laminin (general)", "relationship_type": "protective", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation required for ECM assembly.", "mechanism": "Decreased laminin in BM correlates with BBB breakdown and worsened outcomes.", "protein": "Laminin (general)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10358660" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Aberrant O-mannosylation impairs Dystroglycan's ability to bind laminin in the ECM.", "mechanism": "Mutations or glycosylation defects in Dystroglycan disrupt muscle fiber-ECM adhesion, leading to muscle weakness and wasting.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10377463" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Glycosylation affects integrin folding and ECM binding.", "mechanism": "Mutations in Itga7 disrupt integrin-mediated muscle fiber-ECM adhesion, causing muscle degeneration.", "protein": "Integrin alpha7 (Itga7)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10377463" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "O-mannosylation is essential for Dystroglycan's laminin binding; loss causes disease.", "mechanism": "Defective glycosylation of Dystroglycan leads to impaired muscle function and variable severity of muscle disease.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Therapies may target glycosylation pathways.", "mechanism": "Restoring Dystroglycan glycosylation or function may improve muscle adhesion and reduce dystrophy.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Glycosylation status may affect therapeutic efficacy.", "mechanism": "Enhancing integrin-mediated adhesion can compensate for Dystroglycan defects.", "protein": "Integrin alpha7 (Itga7)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "Glycosylation state affects membrane localization.", "mechanism": "Disorganization and altered localization of Dystroglycan clusters in muscle membrane may correlate with disease severity.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "biomarker", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Compensation depends on glycosylation status of both proteins.", "mechanism": "Functional redundancy with integrin alpha7 can partially compensate for loss of Dystroglycan.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "protective", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "Glycosylation may modulate compensatory adhesion.", "mechanism": "Upregulation or clustering of integrin alpha7 can reduce dystrophy in Dystroglycan-deficient models.", "protein": "Integrin alpha7 (Itga7)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10377463" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "O-mannosylation defects are diagnostic.", "mechanism": "Aberrant glycosylation and altered nanoscale organization of Dystroglycan can serve as diagnostic markers.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "biomarker", "source_pmcid": "PMC10377463" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Glycosylation is required for ECM binding and adhesion.", "mechanism": "Failed adhesion of muscle fibers to the myotendinous junction due to Dystroglycan dysfunction is a defining pathology.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10377463" }, { "confidence": "high", "disease": "ALG1-CDG (Congenital Disorder of Glycosylation type Ik)", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins", "mechanism": "Pathogenic variants in ALG1 impair N-glycan assembly, disrupting glycoprotein biosynthesis and causing multi-organ dysfunction.", "protein": "ALG1 (\u03b21,4 mannosyltransferase)", "protein_enriched": { "function": "Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. 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It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10422073" }, { "confidence": "medium", "disease": "ALG1-CDG (Congenital Disorder of Glycosylation type Ik)", "glycan_involvement": "Defective N-glycosylation", "mechanism": "Hypoglycosylated haptoglobin indicates glycosylation defects.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC10422073" }, { "confidence": "medium", "disease": "ALG1-CDG (Congenital Disorder of Glycosylation type Ik)", "glycan_involvement": "Defective N-glycosylation", "mechanism": "Hypoglycosylated alpha-1 antitrypsin supports diagnosis of CDG.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker", "source_pmcid": "PMC10422073" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "PH domain glycoprotein; glycosylation not directly discussed.", "mechanism": "Intracellular Ca2+ overload forms Ca2+-PIPs, inhibiting AKT membrane localization and disrupting insulin signaling.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "PH domain glycoprotein; glycosylation not directly discussed.", "mechanism": "Ca2+-PIPs prevent IRS1 membrane localization, impairing insulin signaling.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "PH domain glycoprotein; glycosylation not directly discussed.", "mechanism": "Elevated Ca2+ inhibits PLC\u03b4 membrane targeting via Ca2+-PIPs, disrupting insulin signaling.", "protein": "PLC\u03b4", "protein_enriched": { "function": "Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates ost", "gene_name": "GAB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UQC2" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "C2 domain glycoprotein; glycosylation not directly discussed.", "mechanism": "High Ca2+ prevents membrane localization of PI3K-C2\u03b1 (C2 domain) via Ca2+-PIPs.", "protein": "PI3K-C2\u03b1", "protein_enriched": { "function": "Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. F", "gene_name": "PIK3C2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00443" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "X-linked Agammaglobulinemia", "glycan_involvement": "PH domain glycoprotein; glycosylation not directly discussed.", "mechanism": "PH domain mutations abolishing PI(3,4,5)P3 binding cause severe signaling defects.", "protein": "BTK", "protein_enriched": { "function": "Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling tha", "gene_name": "BTK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q06187" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PH domain glycoprotein; glycosylation not directly discussed.", "mechanism": "PH domain mutations (E17K) promote constitutive membrane localization and hyperactivation of AKT.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Phosphatase glycoprotein; glycosylation not directly discussed.", "mechanism": "SHIP2 dephosphorylates PI(3,4,5)P3, inhibiting AKT membrane localization and insulin signaling.", "protein": "SHIP2", "protein_enriched": { "function": "Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regula", "gene_name": "INPPL1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O15357" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Phosphatase glycoprotein; glycosylation not directly discussed.", "mechanism": "PTEN deficiency increases insulin sensitivity and glucose tolerance.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "protective", "source_pmcid": "PMC10474053" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "O-GlcNAc transferase; O-glycosylation directly involved.", "mechanism": "OGT translocates to plasma membrane via PI(3,4,5)P3, inhibiting AKT phosphorylation and insulin signaling.", "protein": "OGT", "relationship_type": "negative regulator", "source_pmcid": "PMC10474053" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Ca2+ ATPase glycoprotein; glycosylation not directly discussed.", "mechanism": "Reduced PMCA1 expression increases cytosolic Ca2+, blood pressure, and vascular remodeling.", "protein": "PMCA1", "protein_enriched": { "function": "Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis (PubMed:35358416). Plays a rol", "gene_name": "ATP2B1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "P20020" }, "relationship_type": "causal", "source_pmcid": "PMC10474053" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect enzyme stability and function.", "mechanism": "Altered aminoacyl-tRNA biosynthesis pathway observed in both early and late-onset T2DM.", "protein": "Aminoacyl-tRNA synthetases", "relationship_type": "biomarker", "source_pmcid": "PMC10477211" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Lysosomal glycoproteins require N-glycosylation for targeting and function.", "mechanism": "Disturbed lysosome pathway in T2DM patients.", "protein": "Lysosomal proteins", "relationship_type": "biomarker", "source_pmcid": "PMC10477211" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "mTOR pathway modulates glycoprotein synthesis.", "mechanism": "Overactivation of mTOR signaling linked to increased branched-chain amino acids in early-onset T2DM.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "causal", "source_pmcid": "PMC10477211" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation required for GLUT trafficking and function.", "mechanism": "Altered glucose uptake and metabolism in T2DM.", "protein": "Glucose transporter (GLUT)", "relationship_type": "causal", "source_pmcid": "PMC10477211" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "O-GlcNAc modification alters protein function and signaling.", "mechanism": "O-GlcNAcylation of proteins linked to proinflammatory transcriptional response in adipocytes.", "protein": "UDP-N-acetylglucosamine (UDP-GlcNAc) modified proteins", "relationship_type": "causal", "source_pmcid": "PMC10477211" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation essential for receptor folding and signaling.", "mechanism": "Insulin resistance is central to T2DM pathogenesis.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC10477211" }, { "confidence": "medium", "disease": "Late-onset T2DM", "glycan_involvement": "Glycosylation affects transporter localization and activity.", "mechanism": "Elevated arginine levels in late-onset T2DM; arginine transporters regulate cellular uptake.", "protein": "Arginine transporter", "relationship_type": "biomarker", "source_pmcid": "PMC10477211" }, { "confidence": "medium", "disease": "Early-onset T2DM", "glycan_involvement": "Glycosylation required for transporter function.", "mechanism": "Increased leucine and isoleucine in early-onset T2DM; transporters mediate uptake.", "protein": "Branched-chain amino acid transporters", "relationship_type": "biomarker", "source_pmcid": "PMC10477211" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation modulates receptor activity.", "mechanism": "Glutamine stimulates GLP-1 release, enhancing insulin secretion.", "protein": "Glucagon-like peptide-1 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10477211" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "PPAR\u03b3 activity may be modulated by glycosylation.", "mechanism": "Pristanic acid activates PPAR\u03b3, improving insulin sensitivity.", "protein": "Peroxisome proliferator-activated receptor gamma (PPAR\u03b3)", "protein_enriched": { "function": "Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) a", "gene_name": "PPARG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37231" }, "relationship_type": "protective", "source_pmcid": "PMC10477211" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever/Dengue Shock Syndrome", "glycan_involvement": "N-glycosylation at Asn-130/Asn-207 critical for secretion and pathogenicity.", "mechanism": "Induces endothelial hyperpermeability and vascular leakage via disruption of intercellular junctions and EGL degradation.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Japanese Encephalitis", "glycan_involvement": "N-glycosylation at Asn-207 required for endothelial damage.", "mechanism": "NS1 and NS1\u2032 disrupt brain endothelial glycocalyx, downregulate sialic acid, upregulate cathepsin L, leading to blood-brain barrier damage.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "West Nile Virus Encephalitis", "glycan_involvement": "N-glycosylation at Asn-130/Asn-175/Asn-207 required for neurovirulence.", "mechanism": "NS1 increases permeability of brain microvascular endothelial cells, promoting neuroinvasiveness.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Zika Congenital Microcephaly", "glycan_involvement": "N-glycosylation stabilizes NS1 hexamer and secretion.", "mechanism": "NS1 disrupts placental and brain endothelial barriers via phosphorylation of \u03b2-catenin/VE-cadherin and ROS production.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "medium", "disease": "Guillain-Barre Syndrome (Zika)", "glycan_involvement": "N-glycosylation required for NS1 secretion and activity.", "mechanism": "NS1-induced endothelial dysfunction may contribute to neurological manifestations.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Yellow Fever", "glycan_involvement": "N-glycosylation at Asn-130/Asn-208 required for neurovirulence.", "mechanism": "NS1 causes dysfunction of liver sinusoidal endothelial cells (HLSEC), contributing to vascular leakage.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Vascular Leakage", "glycan_involvement": "Glycosylation required for NS1 secretion and function.", "mechanism": "NS1 activates complement, increases vasoactive cytokines, and disrupts endothelial junctions.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Endothelial Dysfunction", "glycan_involvement": "N-glycosylation at Asn-207 critical for endocytosis and EGL disruption.", "mechanism": "NS1 interacts with endothelial glycocalyx, disrupts tight and adhesion junctions.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Encephalitis", "glycan_involvement": "Loss of glycosylation sites attenuates neurovirulence.", "mechanism": "NS1 mutations (e.g., P250L, P101K) reduce neuroinvasiveness and encephalitic potential.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation required for NS1 secretion and activity.", "mechanism": "NS1 binds TLR4 on platelets, causing aggregation and bleeding.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC10518729" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Disrupted glycosylation due to Golgi fragmentation affects APP processing.", "mechanism": "GM130 loss or dysfunction leads to Golgi fragmentation, impaired protein trafficking, and increased amyloid-beta production.", "protein": "GM130 (Golgi Matrix Protein 130)", "protein_enriched": { "function": "Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to t", "gene_name": "GOLGA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q08379" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Alters glycosylation and sorting of APP and other proteins.", "mechanism": "Phosphorylation and dysfunction of GRASP65 by CDK5 leads to Golgi fragmentation, increased amyloidogenic APP processing, and tau phosphorylation.", "protein": "GRASP65", "protein_enriched": { "function": "Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi rib", "gene_name": "GORASP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BQQ3" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Affects spike protein glycosylation and trafficking through the Golgi.", "mechanism": "Downregulation of GRASP55 by SARS-CoV-2 enhances viral spike protein trafficking and release.", "protein": "GRASP55", "protein_enriched": { "function": "Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi rib", "gene_name": "GORASP2", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G00912UN", "G08918WF", "G59626AS" ], "uniprot_id": "Q9H8Y8" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Menkes Disease", "glycan_involvement": "Copper-dependent enzymes, many glycoproteins, are misprocessed in the Golgi.", "mechanism": "ATP7A mutations impair copper transport, leading to systemic copper deficiency and neurodegeneration.", "protein": "ATP7A", "protein_enriched": { "function": "Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in", "gene_name": "LPXN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60711" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Wilson's Disease", "glycan_involvement": "Copper-dependent glycoproteins affected in Golgi trafficking.", "mechanism": "ATP7B mutations cause copper accumulation, leading to hepatic and neurological symptoms.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Impaired glycosylation of neuronal glycoproteins.", "mechanism": "COG complex dysfunction alters Golgi trafficking, affecting glycosylation and synaptic function.", "protein": "COG complex subunits", "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy type 1D", "glycan_involvement": "Defective O-mannosyl glycosylation of dystroglycan.", "mechanism": "LARGE mutations disrupt glycosylation of dystroglycan, leading to muscular and cognitive defects.", "protein": "LARGE", "protein_enriched": { "function": "Probable metal transporter", "gene_name": "CNNM1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G80920RR" ], "uniprot_id": "Q9NRU3" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Muscle\u2013Eye\u2013Brain disease (MEB)", "glycan_involvement": "O-mannosyl glycosylation required for function.", "mechanism": "Hypoglycosylation of dystroglycan impairs neuronal migration and synaptic function.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "N- and O-glycosylation modulate APP processing.", "mechanism": "Altered Golgi trafficking and glycosylation of APP increases amyloid-beta production.", "protein": "APP (Amyloid Precursor Protein)", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 19, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO", "G53434XO", "G58001LT", "G02815KT", "G25079LO", "G41247ZX", "G45395BF", "G46503DX", "G62765YT", "G72787SB", "G80920RR", "G88891KO", "G29068FM", "G00666EC", "G35107SO", "G50757KG", "G59277TZ" ], "uniprot_id": "P05067" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Extensive N-glycosylation of spike protein in Golgi.", "mechanism": "Spike protein glycosylation in the Golgi is essential for viral infectivity and immune evasion.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC10605100" }, { "confidence": "high", "disease": "Adipose tissue dysfunction", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation at Thr54 reduces PPAR\u03b3 transcriptional activity, impairing adipocyte differentiation", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10620833" }, { "confidence": "high", "disease": "Adipose tissue dysfunction", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation at Ser180/Ser181 blocks phosphorylation, delaying adipocyte differentiation", "protein": "C/EBP\u03b2", "protein_enriched": { "function": "Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:12048245, PubMed:1741402, PubMed:18647749, PubMed:9374525). Also plays a signifi", "gene_name": "CEBPB", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17676" }, "relationship_type": "causal", "source_pmcid": "PMC10620833" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation via HBP flux regulates AMPK activation, promoting fatty acid oxidation", "protein": "AMPK\u03b1", "protein_enriched": { "function": "Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563", "gene_name": "PRKAA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13131" }, "relationship_type": "protective", "source_pmcid": "PMC10620833" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "O-glycosylation (implied)", "mechanism": "Adiponectin expression increases with O-GlcNAcylation during adipocyte differentiation, supporting insulin sensitivity", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC10620833" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGT-mediated O-GlcNAcylation increases during adipocyte senescence, contributing to age-related adipose dysfunction", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC10620833" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGA inhibition increases O-GlcNAcylation, reducing PPAR\u03b3 activity and adipocyte differentiation", "protein": "OGA", "protein_enriched": { "function": "Cleaves GlcNAc but not GalNAc from O-glycosylated proteins (PubMed:11148210, PubMed:11788610, PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839, PubMed:37962578). Deglycosylates a lar", "gene_name": "OGA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "O60502" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10620833" }, { "confidence": "low", "disease": "Adipose tissue dysfunction", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation of vimentin increases during adipocyte differentiation and senescence", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC10620833" }, { "confidence": "low", "disease": "Adipose tissue dysfunction", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation increases with adipocyte differentiation, possibly affecting metabolism", "protein": "Pyruvate carboxylase", "protein_enriched": { "function": "Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in th", "gene_name": "PC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11498" }, "relationship_type": "biomarker", "source_pmcid": "PMC10620833" }, { "confidence": "low", "disease": "Thermogenic impairment", "glycan_involvement": "PTMs (glycosylation not directly shown)", "mechanism": "UCP1 stability and function are regulated by PTMs; O-GlcNAcylation not directly shown but PTMs implicated in aging BAT", "protein": "UCP1", "protein_enriched": { "function": "Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and", "gene_name": "UCP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25874" }, "relationship_type": "causal", "source_pmcid": "PMC10620833" }, { "confidence": "low", "disease": "Adipose tissue dysfunction", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation increases with adipocyte differentiation", "protein": "Long-chain fatty acid-CoA ligase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10620833" }, { "confidence": "high", "disease": "Retinitis Pigmentosa (non-syndromic)", "glycan_involvement": "Defective O-mannosyl glycosylation of retinal proteins impairs neuroretinal structure/function.", "mechanism": "Mutations in POMGNT1 disrupt O-mannosylation, affecting assembly and organization of basal membranes in the neuroretina, leading to photoreceptor degeneration.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10743436" }, { "confidence": "high", "disease": "Muscle\u2013Eye\u2013Brain Disease", "glycan_involvement": "Impaired O-mannosyl glycosylation affects glycoprotein function in muscle, eye, and brain.", "mechanism": "Loss-of-function mutations in POMGNT1 disrupt O-mannosylation in muscle and nervous tissue, causing multisystem disease.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10743436" }, { "confidence": "high", "disease": "Retinitis Pigmentosa (non-syndromic)", "glycan_involvement": "Partial loss of O-mannosylation activity leads to selective retinal degeneration.", "mechanism": "Hypomorphic POMGNT1 variants (e.g., c.751 + 1G > A, c.1010T > C p.Ile337Thr) cause late-onset RP without extraocular involvement.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC10743436" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Constitutive glycosylation affects receptor function and ligand binding.", "mechanism": "CD36 mediates uptake of oxidized LDL in macrophages, promoting foam cell formation and plaque development.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10744197" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates surface expression and adhesion properties.", "mechanism": "Elevated CD62P on platelets/endothelium indicates increased platelet activation and thrombotic risk in diabetes.", "protein": "CD62P (P-selectin)", "protein_enriched": { "function": "Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand r", "gene_name": "SELP", "glycan_count": 8, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G48414YA", "G57888GL", "G84452RH", "G22310AV", "G45395BF", "G70232NH", "G27058EU", "G64394MX" ], "uniprot_id": "P16109" }, "relationship_type": "biomarker", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation modulates trafficking and activation.", "mechanism": "Higher CD63 levels correlate with long-term diabetic complications including nephropathy.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects adhesive and signaling functions.", "mechanism": "Elevated CD31 in diabetes may link inflammation and thrombosis.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates integrin activation.", "mechanism": "Increased CD49b expression in diabetes enhances platelet adhesion and aggregation.", "protein": "CD49b (Integrin alpha-2)", "protein_enriched": { "function": "Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsi", "gene_name": "ITGA2", "glycan_count": 76, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G00912UN", "G04657PL", "G07246CJ", "G11629QQ", "G15169WU", "G20312EM", "G25451PN", "G27058EU", "G27126ED", "G41071NU", "G45395BF", "G46503DX", "G46524LG", "G57776ZS", "G59626AS", "G62765YT", "G70232NH", "G70441OD", "G70619PT", "G76417NN", "G80075MS", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90659AW", "G92081HT", "G14972EH", "G40834TG", "G59324HL", "G63980BQ", "G80223IX", "G90382BL", "G96577RX", "G01650EU", "G02815KT", "G05724UK", "G18647XP", "G23294PN", "G28541PG", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G64527OM", "G72735IY", "G92050GC", "G70101JE", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G20210JR", "G40574BA", "G42124LM", "G44215PV", "G46902YN", "G48414YA", "G55383ZG", "G59536GA", "G60923RB", "G65184UU", "G67164EE", "G72291OX", "G72790NZ", "G75983OB", "G87051GH", "G92597CK", "G95865ZB", "G64751KD", "G25962JF", "G88891KO", "G49108TO" ], "uniprot_id": "P17301" }, "relationship_type": "biomarker", "source_pmcid": "PMC10744197" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "O-GlcNAcylation at specific sites disrupts phosphorylation and signaling.", "mechanism": "O-GlcNAcylation of IRS proteins impairs insulin signaling, contributing to insulin resistance.", "protein": "IRS proteins", "relationship_type": "causal", "source_pmcid": "PMC10744197" }, { "confidence": "high", "disease": "Vascular Calcification", "glycan_involvement": "O-GlcNAcylation enhances AKT activation.", "mechanism": "O-GlcNAcylation of AKT promotes vascular calcification in diabetes.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Wound Healing Deficits", "glycan_involvement": "O-GlcNAcylation at regulatory sites alters function.", "mechanism": "O-GlcNAcylation of MYPT1 blocks phosphorylation, impairs cellular contraction, and delays wound healing.", "protein": "MYPT1", "protein_enriched": { "function": "Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of ", "gene_name": "PPP1R12A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O14974" }, "relationship_type": "causal", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "O-GlcNAcylation reduces eNOS activity.", "mechanism": "O-GlcNAcylation of eNOS and IRS impairs NO production, increasing thrombosis risk.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal", "source_pmcid": "PMC10744197" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "O-GlcNAcylation prevents c-Myc degradation.", "mechanism": "O-GlcNAcylation stabilizes c-Myc, affecting megakaryocyte differentiation and platelet production.", "protein": "c-Myc", "protein_enriched": { "function": "Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of grow", "gene_name": "MYC", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P01106" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10744197" }, { "confidence": "high", "disease": "Secondary dystroglycanopathies", "glycan_involvement": "Aberrant O-mannosyl glycosylation (matriglycan) on \u03b1-DG", "mechanism": "Mutations in glycosylation enzymes reduce \u03b1-DG glycosylation, impairing ECM binding and membrane stability.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Reduced matriglycan impairs ECM binding", "mechanism": "Disrupted ECM-cytoskeleton linkage due to defective \u03b1-DG glycosylation leads to muscle fragility.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Walker\u2013Warburg syndrome (WWS)", "glycan_involvement": "Defective O-mannosylation", "mechanism": "Hypoglycosylation of \u03b1-DG causes severe congenital muscular dystrophy with brain involvement.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease (MEB)", "glycan_involvement": "Defective O-mannosylation", "mechanism": "Impaired glycosylation of \u03b1-DG disrupts ECM interactions, leading to muscular and neurological symptoms.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Defective O-mannosylation", "mechanism": "FKTN mutations cause \u03b1-DG hypoglycosylation, resulting in muscle and cardiac dysfunction.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Type II lissencephaly", "glycan_involvement": "Impaired matriglycan formation", "mechanism": "Hypoglycosylated \u03b1-DG fails to organize ECM, causing neuronal over-migration and cortical malformation.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Not specified", "mechanism": "Nuclear translocation of \u03b2-DG fragments alters gene expression in prostate cancer cells.", "protein": "Dystroglycan (\u03b2-DG)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Defective O-mannosylation", "mechanism": "Hypoglycosylation of \u03b1-DG leads to age-dependent cardiac dysfunction in FCMD mouse models.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Indirect; DGC stability depends on \u03b1-DG glycosylation", "mechanism": "Destabilization of DGC impairs insulin receptor assembly, contributing to metabolic disorders in muscular dystrophy.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10752950" }, { "confidence": "medium", "disease": "Brain metastasis", "glycan_involvement": "DG-laminin interaction requires proper glycosylation", "mechanism": "Laminin-211/DG axis sequesters YAP, maintaining dormancy of tumor cells in the brain.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "protective", "source_pmcid": "PMC10752950" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycosylated \u03b2-dystroglycan; loss disrupts glycoprotein complex.", "mechanism": "Loss-of-function mutations in dystrophin gene cause DMD by destabilizing the dystrophin glycoprotein complex (DGC), leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Partial retention of DGC and glycoprotein interactions.", "mechanism": "In-frame mutations produce partially functional dystrophin, resulting in milder BMD phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin binds glycosylated \u03b2-dystroglycan, forming a functional complex.", "mechanism": "Utrophin upregulation or gene therapy can compensate for dystrophin loss, restoring DGC and muscle stability.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b2-dystroglycan is heavily glycosylated; glycosylation is essential for DGC assembly.", "mechanism": "Loss of dystrophin impairs \u03b2-dystroglycan membrane localization and stability, disrupting DGC.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Muscle fiber degeneration", "glycan_involvement": "Maintains glycoprotein complex integrity.", "mechanism": "Utrophin expression at the sarcolemma protects against contraction-induced damage in absence of dystrophin.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Loss of glycoprotein complex stability in cardiomyocytes.", "mechanism": "Dystrophin deficiency in cardiac muscle leads to DGC disruption and cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10789850" }, { "confidence": "medium", "disease": "Neuropsychiatric symptoms", "glycan_involvement": "DGC components in neurons are glycosylated.", "mechanism": "Dystrophin isoforms in brain are implicated in synaptic function; loss contributes to neuropsychiatric symptoms in DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Muscle fiber degeneration", "glycan_involvement": "Disruption of glycoprotein-mediated membrane-cytoskeleton linkage.", "mechanism": "Dystrophin loss destabilizes sarcolemma, leading to fiber damage and degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation of \u03b2-dystroglycan is required for its function and interactions.", "mechanism": "Restoring \u03b2-dystroglycan interaction (via utrophin or engineered dystrophin) is a therapeutic strategy.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Forms functional glycoprotein complex with \u03b2-dystroglycan.", "mechanism": "Micro-utrophin gene therapy is less immunogenic than micro-dystrophin and restores muscle function.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10789850" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Differential glycosylation/sialylation of ACE in brain affects conformation and substrate specificity.", "mechanism": "Loss-of-function ACE mutations reduce A\u03b242 cleavage, leading to amyloid accumulation.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "causal", "source_pmcid": "PMC10813023" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation patterns in brain/kidney ACE detectable by mAb conformational fingerprinting.", "mechanism": "Low blood ACE levels indicate increased risk for late-onset AD.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "biomarker", "source_pmcid": "PMC10813023" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects folding and trafficking of ACE to cell surface.", "mechanism": "Transport-deficient ACE mutations may be rescued by chemical/pharmacological chaperones to restore surface ACE.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10813023" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sex-specific glycosylation (sialylation) differences may modulate disease susceptibility.", "mechanism": "Mutations in ACE cytoplasmic tail (e.g., R1250Q, R1257S) alter membrane orientation and may impair A\u03b242 cleavage.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "causal", "source_pmcid": "PMC10813023" }, { "confidence": "high", "disease": "Renal tubular dysgenesis (RTD)", "glycan_involvement": "Glycosylation required for proper ACE folding and surface expression.", "mechanism": "Homozygous or compound heterozygous LoF ACE mutations result in negligible ACE expression, causing RTD.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", 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sclerosis/scleroderma", "glycan_involvement": "Altered glycosylation may affect ACE function in relevant tissues.", "mechanism": "Genetically determined low ACE expression may contribute to pathophysiology.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC10813023" }, { "confidence": "medium", "disease": "Gaucher\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Blood ACE activity is significantly increased in Gaucher\u2019s disease.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "biomarker", "source_pmcid": "PMC10813023" }, { "confidence": "medium", "disease": "Sarcoidosis", "glycan_involvement": "Not specified.", "mechanism": "Blood ACE activity is significantly increased in sarcoidosis.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "biomarker", "source_pmcid": "PMC10813023" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not specified.", "mechanism": "ACE D allele (DD genotype) associated with higher ACE levels and increased lifespan, protective against AD.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "protective", "source_pmcid": "PMC10813023" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation at Asn82, Asn45, Asn131, Asn685, Asn913, Asn1196 impacts folding, trafficking, and mAb recognition.", "mechanism": "ACE mutations (e.g., Y215C, Q1069R) cause transport deficiency, reducing surface ACE and A\u03b242 cleavage.", "protein": "Angiotensin I-converting enzyme (ACE)", "protein_enriched": { "function": "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regula", "gene_name": "ACE", "glycan_count": 124, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G02528FI", "G05962QB", "G07246CJ", "G07755XJ", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G28622IK", "G30740WO", "G35541EV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G49906RN", "G53075ES", "G55132BD", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G98611JV", "G13694XX", "G48414YA", "G62461SM", "G10019LZ", "G11629QQ", "G27058EU", "G72790NZ", "G82830MN", "G88619MM", "G90659AW", "G45889JQ", "G82348BZ", "G00395TQ", "G22310AV", "G42466VF", "G57888GL", "G70888PK", "G83460ZZ", "G02815KT", "G08290VR", "G15664MX", "G24528MX", "G25079LO", "G25418HZ", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G46503DX", "G49642SA", "G54010QB", "G59536GA", "G64527OM", "G70101JE", "G70223PD", "G72747WU", "G80223IX", "G80920RR", "G92050GC", "G37881RL", "G74728JK", "G12045WP", "G22768VO", "G22573RC", "G49955PK", "G65000LJ", "G04657PL", "G05049YU", "G06356OH", "G08918WF", "G27915IV", "G52527GH", "G56784JY", "G57776ZS", "G58087IP", "G59626AS", "G60834IK", "G84225JN", "G85554PZ", "G86182NS", "G93656SY", "G01650EU", "G02886BB", "G10486CT", "G11314AS", "G18647XP", "G29184RN", "G29616NS", "G32156ZV", "G35107SO", "G38663NM", "G39446WN", "G46691LC", "G50282JC", "G58954YZ", "G59924QI", "G72735IY", "G80858MF", "G92406TI", "G95865ZB", "G81315DD", "G29545VG", "G32788FZ", "G75568BH", "G80075MS", "G81637OR", "G93718GY" ], "uniprot_id": "P12821" }, "relationship_type": "causal", "source_pmcid": "PMC10813023" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Loss of O-GlcNAcylation on hepatic proteins disrupts homeostasis.", "mechanism": "Hepatocyte-specific OGT deletion triggers inflammation, apoptosis, and progressive fibrosis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "O-GlcNAcylation is required for hepatocyte survival.", "mechanism": "OGT deficiency leads to oxidative/ER stress, DNA damage, and cell death.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "O-GlcNAcylation modulates stress response proteins.", "mechanism": "OGT loss impairs antioxidant responses, increasing ROS and lipid peroxidation.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Endoplasmic reticulum (ER) stress", "glycan_involvement": "O-GlcNAcylation regulates ER stress signaling.", "mechanism": "OGT deficiency increases CHOP and ER stress-induced apoptosis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "medium", "disease": "Necroptosis", "glycan_involvement": "O-GlcNAcylation suppresses necroptotic pathways.", "mechanism": "OGT deletion increases MLKL expression, promoting necroptosis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "O-GlcNAcylation modulates inflammatory signaling.", "mechanism": "OGT deficiency upregulates inflammatory cytokines and chemokines.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "DNA damage", "glycan_involvement": "O-GlcNAcylation protects against genotoxic stress.", "mechanism": "OGT loss increases \u03b3H2AX, indicating DNA damage.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Impaired gluconeogenesis", "glycan_involvement": "O-GlcNAcylation of Foxo1 is required for gluconeogenic gene expression.", "mechanism": "OGT deficiency reduces Foxo1 O-GlcNAcylation, lowering G6Pase and Pepck expression.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "Sustained loss of O-GlcNAcylation disrupts ECM remodeling.", "mechanism": "Chronic OGT deficiency leads to persistent and advanced fibrosis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Liver fibrosis (nutritional intervention)", "glycan_involvement": "Reduced carbohydrate intake lowers stress in absence of O-GlcNAcylation.", "mechanism": "Ketogenic diet (low carbohydrate) prevents fibrosis in OGT-deficient mice.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "protective", "source_pmcid": "PMC10827605" }, { "confidence": "high", "disease": "Diabetes mellitus (DM)", "glycan_involvement": "TRIB3 expression is linked to O-GlcNAc modification under glucose stress.", "mechanism": "Acts as a nutrient sensor and negative regulator of Akt, promoting insulin resistance and hyperglycemia.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "high", "disease": "Diabetic nephropathy (DN)", "glycan_involvement": "Collagen IV and TGF-\u03b21 are glycoproteins; TRIB3 upregulates their expression.", "mechanism": "Promotes renal fibrosis via upregulation of TGF-\u03b21 and collagen IV through ERK1/2-MAPK signaling.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10859691" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Collagen I/III are glycoproteins; TRIB3 alters their expression.", "mechanism": "Increases cardiac fibrosis and dysfunction by modulating Akt/GSK-3\u03b2 and MAPK pathways.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10859691" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "Not directly specified.", "mechanism": "Accelerates retinal cell loss and capillary degeneration; inhibition improves retinal survival.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not directly specified.", "mechanism": "Promotes foam cell formation and cholesterol accumulation, increasing plaque instability.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "O-GlcNAc modification of proteins is enhanced in IR and linked to TRIB3.", "mechanism": "Inhibits Akt phosphorylation, blocking insulin signaling in muscle, liver, and adipose tissue.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "high", "disease": "\u03b2-cell apoptosis", "glycan_involvement": "Not directly specified.", "mechanism": "Promotes ER stress\u2013induced and FFA-induced \u03b2-cell apoptosis via NF-\u03baB, JNK, and PKC\u03b4 pathways.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Not directly specified.", "mechanism": "Increases proinflammatory cytokines (NF-\u03baB, IL-6, TNF-\u03b1, MCP-1) and ROS production.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Not directly specified.", "mechanism": "Enhances ROS production via NADPH oxidase and impairs antioxidant defenses.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Collagen and fibronectin are glycoproteins; TRIB3 increases their expression.", "mechanism": "Upregulates collagen I/IV and fibronectin, promoting extracellular matrix accumulation.", "protein": "TRIB3", "protein_enriched": { "function": "Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional a", "gene_name": "TRIB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RU7" }, "relationship_type": "causal", "source_pmcid": "PMC10859691" }, { "confidence": "medium", "disease": "cholesterol metabolism disorders", "glycan_involvement": "Glycosylation may regulate SIDT1 trafficking and stability.", "mechanism": "SIDT1 mediates cholesterol transport and hydrolase activity, impacting cholesterol homeostasis.", "protein": "SIDT1", "protein_enriched": { "function": "Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into a", "gene_name": "HPS4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NQG7" }, "relationship_type": "causal", "source_pmcid": "PMC10879482" }, { "confidence": "low", "disease": "cardiovascular disease", "glycan_involvement": "Glycosylation status may modulate SIDT1 activity in vascular tissues.", "mechanism": "Altered SIDT1 function affects cholesterol levels, contributing to cardiovascular risk.", "protein": "SIDT1", "protein_enriched": { "function": "Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into a", "gene_name": "HPS4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NQG7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10879482" }, { "confidence": "low", "disease": "RNA transport-related disorders", "glycan_involvement": "Glycosylation could affect SIDT1 localization and RNA transport efficiency.", "mechanism": "SIDT1 is implicated in RNA transport; dysfunction may lead to disease.", "protein": "SIDT1", "protein_enriched": { "function": "Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into a", "gene_name": "HPS4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NQG7" }, "relationship_type": "causal", "source_pmcid": "PMC10879482" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type Ia (CDG-Ia)", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins due to impaired mannose-1-phosphate production.", "mechanism": "PMM2 mutations reduce enzymatic activity, impairing GDP-mannose synthesis and global N-glycosylation of glycoproteins.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC10905039" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type Ia (CDG-Ia)", "glycan_involvement": "Missing one or two N-glycan chains on transferrin in patient serum.", "mechanism": "Abnormal glycosylation of transferrin leads to altered isoelectric point and loss of N-oligosaccharide chains.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10905039" }, { "confidence": "medium", "disease": "Cerebellar hypoplasia", "glycan_involvement": "Impaired N-glycosylation in neural tissue.", "mechanism": "PMM2 deficiency disrupts glycosylation of proteins critical for cerebellar development.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC10905039" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Global N-glycosylation impairment in liver proteins.", "mechanism": "Defective glycosylation affects hepatic glycoproteins, leading to liver dysfunction.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC10905039" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Defective N-glycosylation in endocrine system.", "mechanism": "Impaired glycosylation of thyroid-related glycoproteins due to PMM2 mutation.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC10905039" }, { "confidence": "high", "disease": "Developmental retardation", "glycan_involvement": "Widespread N-glycosylation defects.", "mechanism": "Global impairment of glycoprotein function in multiple organs due to PMM2 deficiency.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC10905039" }, { "confidence": "medium", "disease": "Congenital disorder of glycosylation type Ia (CDG-Ia)", "glycan_involvement": "Potential to normalize N-glycosylation.", "mechanism": "Restoring PMM2 activity could correct glycosylation defects.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10905039" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies target MOG, leading to inflammatory demyelination in CNS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC10909948" }, { "confidence": "medium", "disease": "Psoriasiform eruption associated with MOGAD", "glycan_involvement": "Glycosylation of MOG may influence immune response, but direct skin antigen is unclear.", "mechanism": "Immune response against MOG may trigger skin inflammation resembling psoriasis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal/trigger", "source_pmcid": "PMC10909948" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect cell surface expression.", "mechanism": "CD20-positive B cells infiltrate CNS lesions in MOGAD, indicating B cell involvement.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC10909948" }, { "confidence": "medium", "disease": "Psoriasiform eruption associated with MOGAD", "glycan_involvement": "CD20 glycosylation may modulate B cell function in skin.", "mechanism": "CD20-positive B cells infiltrate skin lesions in MOGAD-associated psoriasiform eruption.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC10909948" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "CD68 is a glycoprotein; glycosylation may affect macrophage activation.", "mechanism": "CD68-positive macrophages infiltrate CNS lesions in MOGAD.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC10909948" }, { "confidence": "medium", "disease": "Psoriasiform eruption associated with MOGAD", "glycan_involvement": "CD68 glycosylation may influence macrophage function in skin.", "mechanism": "CD68-positive macrophages infiltrate skin lesions in MOGAD-associated psoriasiform eruption.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC10909948" }, { "confidence": "low", "disease": "Psoriasis", "glycan_involvement": "Not applicable.", "mechanism": "No direct link; MOG is not expressed in skin.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "none/unclear", "source_pmcid": "PMC10909948" }, { "confidence": "high", "disease": "PIGA-CDG", "glycan_involvement": "GPI anchor glycosylation is impaired, affecting protein attachment to membrane.", "mechanism": "Loss-of-function mutations in PIGA disrupt GPI anchor biosynthesis, leading to reduced cell surface GPI-anchored proteins.", "protein": "PIGA", "protein_enriched": { "function": "Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidyli", "gene_name": "PIGA", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37287" }, "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "PIGA-CDG", "glycan_involvement": "GPI anchor glycosylation is required for cell surface localization.", "mechanism": "Reduced GPI-anchored protein expression on cell surface due to defective GPI anchor biosynthesis.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "GPI anchor glycosylation is necessary for proper neuronal/glial signaling.", "mechanism": "Deficiency of GPI-anchored proteins in glia leads to seizure phenotype in Drosophila and patients.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "Neurodevelopmental delay", "glycan_involvement": "GPI anchor glycosylation mediates protein localization and function.", "mechanism": "Loss of GPI-anchored proteins impairs cell signaling and adhesion, affecting neurodevelopment.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "Movement disorder", "glycan_involvement": "GPI anchor glycosylation is required for neuronal function.", "mechanism": "Defective GPI-anchored proteins in neurons cause neuromuscular defects and movement disorder.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "medium", "disease": "Congenital malformations", "glycan_involvement": "GPI anchor glycosylation is essential for developmental processes.", "mechanism": "Impaired GPI anchor biosynthesis affects cell adhesion and development.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "medium", "disease": "PIGA-CDG", "glycan_involvement": "BiP is an ER-resident glycoprotein involved in folding GPI-anchored proteins.", "mechanism": "Upregulation of BiP in glia-specific PIGA knockdown suggests increased ER protein folding demand.", "protein": "BiP", "protein_enriched": { "function": "Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Inv", "gene_name": "HSPA5", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P11021" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917494" }, { "confidence": "medium", "disease": "PIGA-CDG", "glycan_involvement": "HYOU1 is an ER-resident glycoprotein involved in protein folding.", "mechanism": "Upregulation of HYOU1 in glia-specific PIGA knockdown indicates increased ER stress response.", "protein": "HYOU1", "protein_enriched": { "function": "Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) ", "gene_name": "HYOU1", "glycan_count": 145, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G15664MX", "G46503DX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G73968GN", "G80920RR", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G25079LO", "G25637MV", "G28541PG", "G31852PQ", "G35029YA", "G39188ZX", "G39446WN", "G41247ZX", "G47644PP", "G50282JC", "G51044QT", "G59924QI", "G64409MC", "G85554PZ", "G88891KO", "G96430BV", "G49108TO", "G00406II", "G00912UN", "G03930BU", "G04657PL", "G06356OH", "G07755XJ", "G10486CT", "G11629QQ", "G22310AV", "G23719VF", "G27058EU", "G28681TP", "G29511JR", "G31916IQ", "G37692EO", "G37881RL", "G40574BA", "G42124LM", "G48414YA", "G48584BU", "G49874UX", "G49955PK", "G57317CE", "G57888GL", "G59626AS", "G62894KT", "G70619PT", "G80333GO", "G83460ZZ", "G84452RH", "G87661QW", "G92050GC", "G95177YH", "G57321FI", "G01485JJ", "G10819WX", "G11314AS", "G14260UH", "G15127JD", "G18647XP", "G24528MX", "G30248BL", "G36379GD", "G40926MX", "G50757KG", "G54010QB", "G57776ZU", "G65000LJ", "G67164EE", "G68735SN", "G72197KC", "G72787SB", "G72790NZ", "G77547TA", "G83633GK", "G84349RE", "G85269DF", "G86182NS", "G90575OW", "G90659AW", "G92275SC", "G94854LT", "G29068FM", "G43417UB", "G02886BB", "G13694XX", "G23863VK", "G34617SM", "G39595FH", "G41882MT", "G46687AB", "G46902YN", "G49018RC", "G62461SM", "G64394MX", "G81263BG", "G93656SY", "G06247RL", "G23505EP", "G36670VW", "G70223PD", "G70232NH", "G74724QE", "G88374WZ", "G91473PK", "G10256JP", "G11870QZ", "G14669DU", "G14972EH", "G20210JR", "G23294PN", "G23432EQ", "G23984SE", "G33416PL", "G43089EG", "G76868JS", "G78787DI", "G05362KT", "G05962QB", "G11101UV", "G36442WJ", "G40206WX", "G46691LC", "G49589RB", "G56307ZW", "G63980BQ", "G68490OW", "G69521XL", "G85282JO", "G94470IW", "G10846ZT", "G41071NU", "G45504EY", "G50045TK", "G90734RJ", "G95865ZB" ], "uniprot_id": "Q9Y4L1" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "PIGA-CDG", "glycan_involvement": "GPI anchor glycosylation is required for C-terminal signal cleavage and membrane attachment.", "mechanism": "Unprocessed GPI-anchored protein precursors are degraded due to failed glycan attachment, contributing to disease.", "protein": "GPI-anchored protein precursors", "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "GPI anchor glycosylation in glia is critical for neuronal excitability regulation.", "mechanism": "Partial loss of PIGA function in glia leads to severe seizure phenotype.", "protein": "PIGA", "protein_enriched": { "function": "Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidyli", "gene_name": "PIGA", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37287" }, "relationship_type": "causal", "source_pmcid": "PMC10917494" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Agrin is a heparan sulfate proteoglycan; glycosylation is essential for ECM interactions.", "mechanism": "Age-dependent reduction of Agrin in skeletal muscle leads to muscle fiber atrophy, decreased strength, and impaired regeneration.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Mini-Agrin retains glycan-binding domains for ECM stabilization.", "mechanism": "Increasing Agrin (mini-Agrin) in aged muscle reverses sarcopenic phenotypes and improves muscle function.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Agrin's glycosylation mediates ECM interactions critical for satellite cell niche.", "mechanism": "Agrin deficiency disrupts muscle satellite cell quiescence and proliferation, reducing regenerative capacity.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "O-mannosylation of \u03b1-DG is essential for Agrin binding and ECM linkage.", "mechanism": "Reduced \u03b1-DG expression in Agrin-deficient and aged muscle impairs membrane integrity and muscle function.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10925061" }, { "confidence": "medium", "disease": "Congenital muscular dystrophy (CMD)", "glycan_involvement": "Glycan-binding domains of Agrin are critical for ECM crosslinking.", "mechanism": "Mini-Agrin overexpression alleviates dystrophic symptoms by stabilizing basal lamina via laminin and \u03b1-DG interactions.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. 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Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "biomarker", "source_pmcid": "PMC10925061" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "MuSK is glycosylated; glycosylation may affect receptor function.", "mechanism": "Reduced MuSK phosphorylation in aged muscle correlates with sarcopenia, but not directly altered by muscle Agrin deficiency.", "protein": "MuSK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Muscle atrophy", "glycan_involvement": "Agrin glycosylation mediates ECM and cytoskeletal interactions.", "mechanism": "Conditional Agrin knockout in muscle progenitors accelerates muscle fiber loss and atrophy.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Glycosylated Agrin supports satellite cell niche integrity.", "mechanism": "Agrin overexpression enhances satellite cell proliferation and muscle regeneration in aged mice.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "protective", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Congenital muscular dystrophy (CMD)", "glycan_involvement": "O-mannosylation is required for functional Agrin-\u03b1-DG interaction.", "mechanism": "Defective glycosylation of \u03b1-DG impairs Agrin binding, leading to CMD pathology.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10925061" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Defective O-glycosylation of \u03b1DG impairs ECM binding.", "mechanism": "Mutations or deficiencies in dystroglycan disrupt ECM binding and sarcolemmal stability, leading to muscle degeneration.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "high", "disease": "Walker\u2013Warburg syndrome (WWS)", "glycan_involvement": "Loss of glycosylated \u03b1DG prevents ECM engagement.", "mechanism": "Total loss of dystroglycan (DAG1 mutation) results in severe muscle and neurological defects, perinatally lethal.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease (MEB)", "glycan_involvement": "Cleavage required for proper glycosylation and function.", "mechanism": "Mutation Cys669Phe in \u03b2DG disrupts \u03b1/\u03b2 cleavage, causing MEB-like symptoms.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "medium", "disease": "Multicystic leukodystrophy", "glycan_involvement": "Cleavage affects glycosylation and ECM binding.", "mechanism": "Cys669Phe mutation in \u03b2DG disrupts disulfide bridge, impairs cleavage, associated with multicystic leukodystrophy.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "medium", "disease": "Late-onset muscular dystrophy", "glycan_involvement": "Affects nuclear localisation, not glycosylation directly.", "mechanism": "Arg776Cys mutation in \u03b2DG cytoplasmic domain (NLS region) leads to late-onset muscular dystrophy.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Proper glycosylation stabilises membrane integrity.", "mechanism": "Maintaining dystroglycan at the sarcolemma can partially compensate for dystrophin loss.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "protective", "source_pmcid": "PMC10931191" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Hypoglycosylation reduces ECM binding.", "mechanism": "Point mutations in \u03b1DG cause hypoglycosylation, resulting in milder dystroglycanopathy symptoms.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Cleavage affects glycoprotein structure and function.", "mechanism": "MMP-mediated cleavage of \u03b2DG produces a ~31 kDa fragment associated with cancer.", "protein": "Dystroglycan (\u03b2DG)", "relationship_type": "biomarker", "source_pmcid": "PMC10931191" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Impaired glycosylation of \u03b1DG.", "mechanism": "Mutations in glycosyltransferases or glycan precursor synthesis enzymes cause secondary/tertiary dystroglycanopathies.", "protein": "Dystroglycan (\u03b1DG/\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "medium", "disease": "Dystroglycanopathies", "glycan_involvement": "\u03b2DG is largely devoid of glycosylation; effects are glycan-independent.", "mechanism": "Deficiency or mutation in \u03b2DG affects nuclear dynamics and may contribute to nuclear abnormalities in disease.", "protein": "Dystroglycan (\u03b2DG)", "relationship_type": "causal", "source_pmcid": "PMC10931191" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "O-glycosylation of \u03b1-Dag1 is essential for ligand binding and synaptic localization.", "mechanism": "Mutations or hypoglycosylation of Dag1 impair extracellular matrix linkage and synaptic organization.", "protein": "Dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "Seizure/Epilepsy", "glycan_involvement": "Glycosylation required for inhibitory synapse assembly; severe hypoglycosylation correlates with seizures.", "mechanism": "Defective inhibitory synapse formation/function increases seizure susceptibility.", "protein": "Dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "Type II lissencephaly", "glycan_involvement": "O-glycosylation of \u03b1-Dag1 required for basement membrane integrity and migration.", "mechanism": "Loss of Dag1 glycosylation disrupts neuronal migration, causing cortical dyslamination.", "protein": "Dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Initiates O-glycosylation of \u03b1-Dag1; loss leads to severe dystroglycanopathy.", "mechanism": "POMT2 mutations prevent initial O-mannosylation of Dag1, abolishing glycan chain formation.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "Partial reduction in O-glycosylation of \u03b1-Dag1; mild impact on synapse function.", "mechanism": "B4GAT1 missense mutation reduces Dag1 glycosylation, causing mild muscular dystrophy and synaptic defects.", "protein": "B4GAT1", "protein_enriched": { "function": "Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling", "gene_name": "ABRA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N0Z2" }, "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "Partial reduction in O-glycosylation of \u03b1-Dag1; mild impact on synapse function.", "mechanism": "FKRP mutation reduces Dag1 glycosylation, leading to mild muscular dystrophy and minor synaptic defects.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "Walker-Warburg Syndrome", "glycan_involvement": "Loss of O-glycosylation disrupts synaptic and structural brain development.", "mechanism": "Severe Dag1 hypoglycosylation causes brain malformations and neurological symptoms.", "protein": "Dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "Muscle-Eye-Brain disease", "glycan_involvement": "O-glycosylation of \u03b1-Dag1 is essential for tissue integrity.", "mechanism": "Defective glycosylation of Dag1 leads to muscle, eye, and brain abnormalities.", "protein": "Dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Interacts with glycosylated Dag1 via intracellular domain.", "mechanism": "Dystrophin mutations disrupt DGC, affecting inhibitory synapse development and cognitive function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC10942650" }, { "confidence": "medium", "disease": "Seizure/Epilepsy", "glycan_involvement": "Glycosylation status of \u03b1-Dag1 can serve as a biomarker for neurological risk.", "mechanism": "Degree of Dag1 glycosylation correlates with seizure susceptibility.", "protein": "Dystroglycan (Dag1)", "relationship_type": "biomarker", "source_pmcid": "PMC10942650" }, { "confidence": "high", "disease": "PIGN-Congenital Disorder of Glycosylation (PIGN-CDG, Bella-Noah Syndrome)", "glycan_involvement": "Defective addition of phosphoethanolamine to mannose in GPI-anchor glycan structure.", "mechanism": "Biallelic pathogenic variants in PIGN impair GPI-anchor biosynthesis, leading to defective cell surface protein anchoring and multisystemic symptoms.", "protein": "PIGN (Glycosylphosphatidylinositol ethanolamine phosphate transferase 1)", "protein_enriched": { "function": "Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and ", "gene_name": "SLC52A2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "Q9HAB3" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "high", "disease": "Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1)", "glycan_involvement": "Impaired GPI-anchor glycan biosynthesis.", "mechanism": "Mutations in PIGN cause GPI-anchor deficiency, resulting in MCAHS1 phenotype.", "protein": "PIGN (Glycosylphosphatidylinositol ethanolamine phosphate transferase 1)", "protein_enriched": { "function": "Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and ", "gene_name": "SLC52A2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "Q9HAB3" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "medium", "disease": "Fryns syndrome", "glycan_involvement": "Defective GPI-anchor glycan assembly.", "mechanism": "PIGN mutations can result in Fryns syndrome via GPI-anchor deficiency.", "protein": "PIGN (Glycosylphosphatidylinositol ethanolamine phosphate transferase 1)", "protein_enriched": { "function": "Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and ", "gene_name": "SLC52A2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "Q9HAB3" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "medium", "disease": "Neuronal ceroid lipofuscinosis (not detailed in article)", "glycan_involvement": "Indirect; CLN6 is involved in lysosomal function, which may affect glycoprotein turnover.", "mechanism": "Pathogenic CLN6 variants are associated with neuronal ceroid lipofuscinosis.", "protein": "CLN6", "protein_enriched": { "function": "", "gene_name": "CLN6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NWW5" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "medium", "disease": "Leukodystrophy (not detailed in article)", "glycan_involvement": "Indirect; impacts sphingolipid glycosylation.", "mechanism": "Pathogenic FA2H variants cause leukodystrophy via defective fatty acid hydroxylation.", "protein": "FA2H", "protein_enriched": { "function": "Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B moti", "gene_name": "HIVEP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q5T1R4" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "medium", "disease": "Glycogen storage disease type II (Pompe disease, not detailed in article)", "glycan_involvement": "GAA is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Pathogenic GAA variants cause lysosomal glycogen accumulation.", "protein": "GAA", "protein_enriched": { "function": "Essential for the degradation of glycogen in lysosomes (PubMed:14695532, PubMed:18429042, PubMed:1856189, PubMed:7717400). Has highest activity on alpha-1,4-linked glycosidic linkages, but can also hy", "gene_name": "GAA", "glycan_count": 86, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G03238UC", "G05049YU", "G06110VR", "G14343MU", "G14669DU", "G25637MV", "G28681TP", "G29545VG", "G30084YQ", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G66537LK", "G74724QE", "G83633GK", "G84349RE", "G90575OW", "G90734RJ", "G92050GC", "G92275SC", "G96430BV", "G98129XB", "G49108TO", "G36437LH", "G93993PD", "G00912UN", "G01650EU", "G04854VP", "G10486CT", "G11314AS", "G18647XP", "G23294PN", "G31986NC", "G37399XV", "G41071NU", "G49906RN", "G55220VL", "G60145BJ", "G65184UU", "G70101JE", "G70441OD", "G72291OX", "G72787SB", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G84452RH", "G84820NF", "G87661QW", "G94470IW", "G95865ZB", "G57321FI", "G05724UK", "G25079LO", "G30970QQ", "G33609NS", "G36442WJ", "G43769HG", "G46503DX", "G48213MO", "G49018RC", "G72735IY", "G80075MS", "G81315DD", "G10300DY", "G84852GW", "G08290VR", "G42124LM", "G45395BF", "G47644PP", "G53434XO", "G66538GV", "G71784JC", "G23719VF", "G29299MO", "G47950XN", "G59324HL", "G70232NH", "G90382BL" ], "uniprot_id": "P10253" }, "relationship_type": "causal", "source_pmcid": "PMC10951506" }, { "confidence": "high", "disease": "Encephalocele", "glycan_involvement": "Defective O-glycosylation of \u03b1-dystroglycan due to B3GALNT2 mutations", "mechanism": "Compound heterozygous loss-of-function mutations in B3GALNT2 cause defective O-glycosylation of \u03b1-dystroglycan, leading to neural tube defects including encephalocele.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "medium", "disease": "Hydrocephalus", "glycan_involvement": "Impaired O-glycosylation of \u03b1-dystroglycan", "mechanism": "B3GALNT2 mutations result in abnormal glycosylation of \u03b1-dystroglycan, associated with fetal hydrocephalus.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Severe reduction in O-glycosylation of \u03b1-dystroglycan", "mechanism": "Biallelic loss-of-function mutations in B3GALNT2 cause severe dystroglycanopathy (WWS) via \u03b1-dystroglycan hypoglycosylation.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "high", "disease": "Muscle-eye-brain disease (MEB)", "glycan_involvement": "Partial impairment of O-glycosylation of \u03b1-dystroglycan", "mechanism": "Compound heterozygous missense mutations in B3GALNT2 cause MEB via partial loss of \u03b1-dystroglycan glycosylation.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "medium", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Impaired O-glycosylation of \u03b1-dystroglycan", "mechanism": "B3GALNT2 mutations can cause FCMD-like dystroglycanopathy phenotypes through defective glycosylation of \u03b1-dystroglycan.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Mild reduction in O-glycosylation of \u03b1-dystroglycan", "mechanism": "Milder B3GALNT2 mutations may result in LGMD via reduced glycosylation of \u03b1-dystroglycan.", "protein": "B3GALNT2", "protein_enriched": { "function": "Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward", "gene_name": "B3GALNT2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "Q8NCR0" }, "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "high", "disease": "Dystroglycanopathies (WWS, MEB, FCMD, LGMD)", "glycan_involvement": "O-glycosylation is essential for \u03b1-dystroglycan function", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan impairs its function in muscle and brain development, causing various dystroglycanopathies.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC10997814" }, { "confidence": "high", "disease": "Nemaline Myopathy", "glycan_involvement": "No glycosylation involvement reported for ACTA1 in this context.", "mechanism": "Mutations in ACTA1 disrupt thin filament structure in muscle, leading to muscle weakness and formation of nemaline bodies.", "protein": "ACTA1 (Alpha-actin 1)", "protein_enriched": { "function": "Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells", "gene_name": "ACTA2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G05049YU", "G49108TO", "G70994MS" ], "uniprot_id": "P62736" }, "relationship_type": "causal", "source_pmcid": "PMC11040521" }, { "confidence": "high", "disease": "Nemaline Myopathy", "glycan_involvement": "No glycosylation involvement reported for NEB in this context.", "mechanism": "Mutations in NEB affect sarcomere thin filament stability, causing muscle weakness and nemaline body formation.", "protein": "NEB (Nebulin)", "protein_enriched": { "function": "This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin", "gene_name": "NEB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20929" }, "relationship_type": "causal", "source_pmcid": "PMC11040521" }, { "confidence": "high", "disease": "Bolivian hemorrhagic fever", "glycan_involvement": "Sialic acid residues on CD71 mediate viral binding.", "mechanism": "CD71 serves as entry receptor for Machupo virus (New World mammarenavirus) via GP binding.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Argentinian hemorrhagic fever", "glycan_involvement": "Sialic acid residues facilitate viral GP attachment.", "mechanism": "CD71 mediates Jun\u00edn virus entry into host cells.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Brazil hemorrhagic fever", "glycan_involvement": "Sialic acid residues involved in viral binding.", "mechanism": "CD71 is the entry receptor for Sabi\u00e1 virus.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Venezuelan hemorrhagic fever", "glycan_involvement": "Sialic acid residues on CD71 are critical for GP binding.", "mechanism": "CD71 mediates Guanarito virus entry.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Sialic acid residues on CD71 facilitate viral penetration.", "mechanism": "Influenza A virus utilizes CD71 for host cell entry.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Sialic acid residues mediate interaction.", "mechanism": "Rabies lyssavirus binds CD71 for cell entry.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Sialic acid residues on CD71 involved in viral binding.", "mechanism": "CD71 acts as a port of endocytosis for hepatitis C virus, synergizing with CD81.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Sialic acid residues on CD71 facilitate Spike binding.", "mechanism": "SARS-CoV-2 Spike protein binds CD71 with high affinity for cell entry.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Lassa hemorrhagic fever", "glycan_involvement": "Glycosylation of \u03b1-dystroglycan is essential for viral docking.", "mechanism": "Lassa virus uses \u03b1-dystroglycan as its cellular receptor for entry.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "Lymphocytic choriomeningitis", "glycan_involvement": "Glycosylation state of \u03b1-dystroglycan determines receptor function.", "mechanism": "LCM virus binds \u03b1-dystroglycan for host cell entry.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11069603" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation type Ii)", "glycan_involvement": "Defective N-glycosylation leads to truncated glycan structures on transferrin.", "mechanism": "Abnormal transferrin glycoform with linear heptasaccharide (NeuAc-Gal-GlcNAc-Man2-GlcNAc2) is specific for ALG2-CDG diagnosis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11102957" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation type Ii)", "glycan_involvement": "Deficiency in mannose addition during lipid-linked oligosaccharide 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"G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC11102957" }, { "confidence": "medium", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation type Ii)", "glycan_involvement": "Generalized N-glycosylation abnormality.", "mechanism": "Increased abnormal linear and fucosylated glycans detected on IgG in plasma.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11102957" }, { "confidence": "high", "disease": "Global Developmental Delay", "glycan_involvement": "N-glycosylation essential for normal brain development.", "mechanism": "Defective N-glycosylation impairs neuronal development and cognitive function.", "protein": "ALG2 (\u03b11,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC11102957" }, { "confidence": "medium", "disease": "Seizures", "glycan_involvement": "Defective N-glycosylation in CNS.", "mechanism": "Impaired glycosylation of neuronal proteins leads to seizure susceptibility.", "protein": "ALG2 (\u03b11,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC11102957" }, { "confidence": "medium", "disease": "Hypotonia", "glycan_involvement": "Impaired N-glycosylation of muscle proteins.", "mechanism": "Defective glycosylation affects muscle and neuromuscular junction function.", "protein": "ALG2 (\u03b11,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC11102957" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation type Ii)", "glycan_involvement": "Altered N-glycan composition on transferrin.", "mechanism": "Carbohydrate-deficient transferrin (CDT) pattern is diagnostic for CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11102957" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation type Ii)", "glycan_involvement": "Reduced N-glycosylation capacity.", "mechanism": "Novel and known pathogenic variants reduce ALG2 protein stability and abundance.", "protein": "ALG2 (\u03b11,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC11102957" }, { "confidence": "high", "disease": "steatosis", "glycan_involvement": "Loss of N-glycan sialylation on VEGFR2 increases receptor activation.", "mechanism": "Desialylation of VEGFR2 leads to enhanced phosphorylation and overstimulated VEGF signaling, disrupting hepatocyte zonation and causing lipid accumulation.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "high", "disease": "steatosis", "glycan_involvement": "CMP-sialic acid transport deficiency reduces sialylation of glycoproteins.", "mechanism": "Slc35a1 deficiency impairs sialylation in LSECs, leading to altered VEGFR2 signaling and hepatocyte lipid droplet accumulation.", "protein": "Slc35a1", "protein_enriched": { "function": "Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP (Pu", "gene_name": "SLC35A3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2D2" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "high", "disease": "dyslipidemia", "glycan_involvement": "N-glycan sialylation regulates VEGFR2 activity.", "mechanism": "Desialylated VEGFR2 in LSECs leads to abnormal lipid metabolism and dyslipidemia.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "medium", "disease": "focal hepatic necrosis", "glycan_involvement": "Defective sialylation of glycoproteins in LSECs.", "mechanism": "Slc35a1 knockout in LSECs causes loss of endothelial identity and focal necrosis.", "protein": "Slc35a1", "protein_enriched": { "function": "Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP (Pu", "gene_name": "SLC35A3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2D2" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "medium", "disease": "steatosis", "glycan_involvement": "Lyve1 is a glycoprotein marker of fenestrated LSECs.", "mechanism": "Loss of Lyve1 expression in LSECs correlates with altered zonation and lipid accumulation.", "protein": "Lyve1", "protein_enriched": { "function": "Ligand-specific transporter trafficking between intracellular organelles (TGN) and the plasma membrane. Plays a role in autocrine regulation of cell growth mediated by growth regulators containing cel", "gene_name": "LYVE1", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G16407EV", "G25637MV", "G37881RL", "G00912UN", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G13728QT", "G22310AV", "G27058EU", "G27947YN", "G31665QC", "G33791AF", "G37818NZ", "G40926MX", "G46842SD", "G47518TP", "G56784JY", "G59536GA", "G59626AS", "G80920RR", "G86795LJ", "G86880BF", "G89205CJ", "G99668VU" ], "uniprot_id": "Q9Y5Y7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11127617" }, { "confidence": "medium", "disease": "steatosis", "glycan_involvement": "CD34 is a glycoprotein marker of non-fenestrated endothelium.", "mechanism": "Gain of CD34 expression in LSECs indicates loss of normal endothelial identity in steatotic livers.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC11127617" }, { "confidence": "high", "disease": "congenital disorder of glycosylation type II", "glycan_involvement": "Global defect in glycoprotein sialylation.", "mechanism": "Human SLC35A1 deficiency causes CDG-II, though no liver phenotype reported.", "protein": "Slc35a1", "protein_enriched": { "function": "Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP (Pu", "gene_name": "SLC35A3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2D2" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "medium", "disease": "metabolic dysfunction\u2013associated steatotic liver disease", "glycan_involvement": "N-glycan sialylation modulates VEGFR2 signaling.", "mechanism": "Altered VEGFR2 glycosylation may contribute to disrupted zonation and lipid metabolism.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "high", "disease": "dyslipidemia", "glycan_involvement": "Impaired sialylation of glycoproteins.", "mechanism": "Slc35a1 deficiency in LSECs leads to abnormal lipid metabolism and dyslipidemia.", "protein": "Slc35a1", "protein_enriched": { "function": "Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP (Pu", "gene_name": "SLC35A3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2D2" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "medium", "disease": "focal hepatic necrosis", "glycan_involvement": "Loss of N-glycan sialylation.", "mechanism": "Desialylated VEGFR2 signaling disrupts endothelial identity, contributing to necrosis.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal", "source_pmcid": "PMC11127617" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Catalyzes O-GlcNAcylation of proteins, increasing glycosylation in DR.", "mechanism": "OGT expression is upregulated in DR, correlates with increased O-GlcNAc modification and photoreceptor degeneration.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Removes O-GlcNAc from proteins; decreased activity increases glycosylation.", "mechanism": "OGA expression is downregulated in DR, leading to accumulation of O-GlcNAc-modified proteins.", "protein": "O-GlcNAcase (OGA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "O-glycosylation (O-GlcNAc) on serine/threonine residues.", "mechanism": "Increased O-GlcNAc modification promotes photoreceptor apoptosis and degeneration.", "protein": "O-GlcNAc-modified proteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Regulates O-GlcNAcylation via GFAT/TXNIP axis.", "mechanism": "AMPK activation reduces O-GlcNAc modification, photoreceptor apoptosis, and neovascularization.", "protein": "AMPK\u03b11", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Controls UDP-GlcNAc synthesis for O-glycosylation.", "mechanism": "GFAT upregulation increases hexosamine pathway flux, elevating O-GlcNAc modification in DR.", "protein": "GFAT", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "O-GlcNAcylation of TXNIP at multiple predicted sites.", "mechanism": "TXNIP interacts with O-GlcNAc modification; its O-GlcNAcylation promotes photoreceptor apoptosis.", "protein": "TXNIP", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11173153" }, { "confidence": "medium", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Indirectly regulated by O-GlcNAcylation signaling.", "mechanism": "Bax expression increases with O-GlcNAc modification, promoting apoptosis in photoreceptors.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC11173153" }, { "confidence": "medium", "disease": "Diabetic retinopathy (DR)", "glycan_involvement": "Indirectly regulated by O-GlcNAcylation signaling.", "mechanism": "Bcl2 expression decreases with increased O-GlcNAc modification, reducing anti-apoptotic protection.", "protein": "Bcl2", "protein_enriched": { "function": "Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondria", "gene_name": "BCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10415" }, "relationship_type": "protective", "source_pmcid": "PMC11173153" }, { "confidence": "medium", "disease": "Neovascularization (retinal)", "glycan_involvement": "Potential O-glycosylation involvement in tight junction regulation.", "mechanism": "ZO-1 distribution altered in HUVECs exposed to conditioned medium from high-glucose-treated photoreceptors; reversed by AMPK activation.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC11173153" }, { "confidence": "high", "disease": "Neurodegeneration (retinal)", "glycan_involvement": "O-glycosylation (O-GlcNAc) on photoreceptor proteins.", "mechanism": "O-GlcNAc modification of photoreceptor proteins increases apoptosis and degeneration under high glucose.", "protein": "Photoreceptor cell proteins (661 w cells)", "relationship_type": "causal", "source_pmcid": "PMC11173153" }, { "confidence": "medium", "disease": "Intellectual Deficiency (ID)", "glycan_involvement": "O-glycosylation and methylation of histones regulate gene expression epigenetically.", "mechanism": "Altered histone methylation and glycosylation modulate chromatin state, affecting neuronal maturation speed and cognitive development.", "protein": "Histones", "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Autism Spectrum Disorders (ASD)", "glycan_involvement": "Potential glycosylation affects protein stability and synaptic localization.", "mechanism": "SRGAP2C delays dendritic spine maturation and synaptogenesis, contributing to altered neuronal connectivity.", "protein": "SRGAP2C", "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Intellectual Deficiency (ID)", "glycan_involvement": "Glycosylation may regulate LDHA activity and stability.", "mechanism": "Inhibition of LDHA enhances mitochondrial metabolism, accelerating neuronal maturation.", "protein": "LDHA", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHA", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G43223CG", "G57776ZS", "G84225JN", "G92406TI" ], "uniprot_id": "P00338" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Intellectual Deficiency (ID)", "glycan_involvement": "Glycosylation may affect LDHB function.", "mechanism": "Overexpression of LDHB increases mitochondrial oxidative activity, promoting neuronal differentiation.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11190843" }, { "confidence": "high", "disease": "Mitochondrial Disease", "glycan_involvement": "Glycosylation may influence complex assembly and activity.", "mechanism": "Inhibition of Complex I reduces mitochondrial activity, slowing neuronal development and causing neurodevelopmental defects.", "protein": "Mitochondrial ETC Complex I", "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Intellectual Deficiency (ID)", "glycan_involvement": "Glycosylation may modulate complex function.", "mechanism": "Lower activity in human neurons correlates with slower maturation and cognitive development.", "protein": "Mitochondrial ETC Complex IV", "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "low", "disease": "Autism Spectrum Disorders (ASD)", "glycan_involvement": "Glycosylation may affect synaptic targeting.", "mechanism": "Human-specific synaptic RhoGEFs are implicated in synaptic development and ASD risk.", "protein": "RhoGEFs", "relationship_type": "biomarker", "source_pmcid": "PMC11190843" }, { "confidence": "low", "disease": "Intellectual Deficiency (ID)", "glycan_involvement": "Glycosylation may regulate transcription factor activity.", "mechanism": "Human-specific expression patterns of GATA3 may influence neuronal development.", "protein": "GATA3", "protein_enriched": { "function": "Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation proc", "gene_name": "GATA3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23771" }, "relationship_type": "biomarker", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Fragile X Syndrome", "glycan_involvement": "Glycosylation may affect FMRP function and localization.", "mechanism": "Mutations in FMRP disrupt mitochondrial metabolism and neuronal maturation.", "protein": "Fragile X Mental Retardation Protein (FMRP)", "protein_enriched": { "function": "Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stabilit", "gene_name": "FMR1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G55101FB", "G49108TO" ], "uniprot_id": "Q06787" }, "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "medium", "disease": "Rett Syndrome", "glycan_involvement": "O-glycosylation of histones modulates chromatin structure.", "mechanism": "Altered histone PTMs, including glycosylation, affect neuronal gene expression and maturation.", "protein": "Histones", "relationship_type": "causal", "source_pmcid": "PMC11190843" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "O-GlcNAcylation of osteoclast markers", "mechanism": "OGT inhibition reduces osteoclast differentiation and bone resorption.", "protein": "OGT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11194333" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "O-GlcNAcylation at Ser/Thr residues", "mechanism": "O-GlcNAcylation enhances Runx2 transcriptional activity, promoting osteoblast differentiation and bone formation.", "protein": "Runx2", "protein_enriched": { "function": "Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). Essential for the maturation of osteoblasts and both intra", "gene_name": "RUNX2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13950" }, "relationship_type": "causal", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "O-GlcNAcylation at Asn346", "mechanism": "O-GlcNAcylation of SIRT1 increases deacetylase activity, suppressing RANKL-mediated osteoclast differentiation.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC11194333" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "O-GlcNAcylation of p65 subunit", "mechanism": "O-GlcNAcylation promotes nuclear translocation and transcriptional activity, enhancing inflammation.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "causal", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "O-GlcNAcylation of TAB1", "mechanism": "O-GlcNAcylation of TAB1 promotes TAK1 activation and downstream inflammatory signaling.", "protein": "TAB1", "protein_enriched": { "function": "Key adapter protein that plays an essential role in JNK and NF-kappa-B activation and proinflammatory cytokines production in response to stimulation with TLRs and cytokines (PubMed:22307082, PubMed:2", "gene_name": "TAB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q15750" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11194333" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "O-GlcNAcylation of tumor-associated proteins", "mechanism": "High OGT expression correlates with poor prognosis and increased proliferation.", "protein": "OGT", "relationship_type": "biomarker", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "O-GlcNAc removal from proteins", "mechanism": "High OGA expression is associated with better prognosis and response to chemotherapy.", "protein": "OGA", "protein_enriched": { "function": "Cleaves GlcNAc but not GalNAc from O-glycosylated proteins (PubMed:11148210, PubMed:11788610, PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839, PubMed:37962578). Deglycosylates a lar", "gene_name": "OGA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "O60502" }, "relationship_type": "protective", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Indirectly increases O-GlcNAcylation", "mechanism": "ROCK2 stabilizes OGT, increasing O-GlcNAcylation and promoting tumor growth and drug resistance.", "protein": "ROCK2", "protein_enriched": { "function": "Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis (By simil", "gene_name": "CXCL16", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G08918WF", "G43223CG", "G62765YT" ], "uniprot_id": "Q9H2A7" }, "relationship_type": "causal", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Intervertebral disc degeneration", "glycan_involvement": "O-GlcNAcylation of Sox9", "mechanism": "O-GlcNAcylation inhibits Sox9 activity, reducing COL-II expression and promoting degeneration.", "protein": "Sox9", "protein_enriched": { "function": "Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:24038782). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enha", "gene_name": "SOX9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48436" }, "relationship_type": "causal", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Intervertebral disc degeneration", "glycan_involvement": "O-GlcNAcylation of FAM134B", "mechanism": "O-GlcNAcylation stabilizes FAM134B, promoting autophagy and inhibiting apoptosis/senescence.", "protein": "FAM134B", "protein_enriched": { "function": "Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (PubMed:11095750). Downstream effector of Notch signaling required for cardiovascular development. Spe", "gene_name": "HEY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J3" }, "relationship_type": "protective", "source_pmcid": "PMC11194333" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Lewis Y is a glycan epitope on glycoproteins; glycosylation is essential for antigenicity.", "mechanism": "Surface glycoprotein expressed on AML blasts; targeted by CAR-T cells.", "protein": "Lewis Y antigen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Sialylated glycoprotein; glycosylation affects ligand binding and immune recognition.", "mechanism": "Highly expressed on AML blasts; CAR-T targeting leads to blast reduction.", "protein": "CD33 (Siglec-3)", "protein_enriched": { "function": "Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state (PubMed:10611343, PubMed:11320212, PubM", "gene_name": "CD33", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G59626AS", "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "P20138" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Surface glycoprotein; glycosylation may affect cell adhesion and immune interactions.", "mechanism": "Expressed on AML blasts; CAR-T targeting clears CD38+ blasts.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycoprotein; glycosylation may modulate immune cell interactions.", "mechanism": "Aberrantly expressed in AML; associated with aggressive disease and therapy resistance.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "CD44 is heavily glycosylated; glycosylation and splicing create neo-epitopes.", "mechanism": "Splice variant expressed on AML cells; required for tumor growth.", "protein": "CD44v6", "protein_enriched": { "function": "Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:197", "gene_name": "CD44", "glycan_count": 81, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G57321FI", "G53434XO", "G43417UB", "G48414YA", "G10486CT", "G00912UN", "G02030ZB", "G05962QB", "G06247RL", "G06330RB", "G06356OH", "G08918WF", "G11629QQ", "G13694XX", "G15169WU", "G20312EM", "G22310AV", "G23010ZW", "G24517ZG", "G25418HZ", "G25451PN", "G27058EU", "G27947YN", "G33791AF", "G37818NZ", "G37881RL", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G43223CG", "G44215PV", "G45395BF", "G46524LG", "G47012YE", "G47518TP", "G51413EV", "G52527GH", "G53075ES", "G55412XP", "G56784JY", "G57776ZS", "G57888GL", "G59324HL", "G59536GA", "G59626AS", "G60834IK", "G62461SM", "G64394MX", "G65019XG", "G66163OV", "G66760KM", "G69521XL", "G70232NH", "G70888PK", "G75983OB", "G76417NN", "G77547TA", "G77582RK", "G79666IR", "G80075MS", "G80223IX", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G86880BF", "G87123QX", "G90093AU", "G90382BL", "G91344EV", "G91473PK", "G94831VI", "G95133RI", "G96577RX", "G98611JV", "G56770VP", "G80920RR", "G71784JC", "G49108TO" ], "uniprot_id": "P16070" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Membrane glycoprotein; glycosylation may affect receptor function.", "mechanism": "Overexpressed on AML blasts and LSCs; associated with poor prognosis.", "protein": "CD123 (IL3R-\u03b1)", "protein_enriched": { "function": "Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-r", "gene_name": "IL3RA", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G23711JB" ], "uniprot_id": "P26951" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "C-type lectin-like glycoprotein; glycosylation may affect ligand binding.", "mechanism": "Expressed on AML blasts and LSCs; CAR-T targeting prolongs survival in models.", "protein": "CLL-1 (CLEC12A)", "protein_enriched": { "function": "C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner (PubMed:27015765). Involved in regulating im", "gene_name": "CLEC4A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UMR7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "medium", "disease": "Mixed-Phenotype Acute Leukemia", "glycan_involvement": "Surface glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Aberrant expression in t(8;21) AML and mixed-phenotype leukemia; CAR-T targeting induces remission.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "TNF receptor family glycoprotein; glycosylation may affect receptor-ligand interactions.", "mechanism": "Expressed on AML blasts and LSCs; not on normal HSCs; CAR-T targeting shows anti-leukemia activity.", "protein": "CD70", "protein_enriched": { "function": "Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells (PubMed:28011863, PubMed:28011864, PubMed:8387892). The CD7", "gene_name": "CD70", "glycan_count": 16, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G06247RL", "G08918WF", "G27058EU", "G29299MO", "G40574BA", "G45395BF", "G57776ZS", "G63041LO", "G69521XL", "G79666IR", "G41247ZX", "G57321FI", "G49108TO" ], "uniprot_id": "P32970" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "low", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Sialic acid-binding glycoprotein; glycosylation critical for ligand recognition.", "mechanism": "Expressed on AML cells; anti-Siglec-6 CAR-T cells show killing activity in vitro.", "protein": "Siglec-6", "protein_enriched": { "function": "Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein f", "gene_name": "DYNLRB1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NP97" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200794" }, { "confidence": "high", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation regulates VCAM-1 stability and cell surface expression, impacting adhesion.", "mechanism": "VCAM-1 mediates adhesion of sickled erythrocytes and leukocytes to endothelium, promoting vaso-occlusion and stroke risk.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203960" }, { "confidence": "high", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "TEK variants disrupt vascular quiescence, increasing endothelial permeability and stroke risk.", "protein": "TEK (Tie2)", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading,", "gene_name": "TEK", "glycan_count": 11, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G56784JY", "G33791AF", "G37881RL", "G45395BF", "G52527GH", "G22310AV", "G72291OX", "G82463GQ", "G81315DD", "G11629QQ", "G38663NM" ], "uniprot_id": "Q02763" }, "relationship_type": "causal", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation affects membrane localization and interaction with plasminogen.", "mechanism": "ANXA2 variants increase plasmin generation, leading to hypercoagulation and cerebrovascular events.", "protein": "ANXA2 (Annexin A2)", "protein_enriched": { "function": "Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress respons", "gene_name": "ANXA2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P07355" }, "relationship_type": "causal", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "N-glycosylation required for enzyme activity and secretion.", "mechanism": "ENPP1 variants modulate extracellular ATP breakdown, influencing vascular calcification and stroke risk.", "protein": "ENPP1", "protein_enriched": { "function": "Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone min", "gene_name": "ENPP1", "glycan_count": 45, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G11629QQ", "G20312EM", "G25418HZ", "G25451PN", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G47518TP", "G60177UT", "G68490OW", "G77582RK", "G83229XP", "G83460ZZ", "G84452RH", "G86795LJ", "G87661QW", "G92081HT", "G92135MA", "G95133RI", "G02886BB", "G05724UK", "G07246CJ", "G10773YW", "G20210JR", "G28541PG", "G47644PP", "G49018RC", "G51640FO", "G59924QI", "G63041LO", "G70619PT", "G72747WU", "G83646BJ", "G84820NF", "G90659AW", "G92062TF", "G96091TT", "G46503DX", "G70232NH", "G85282JO", "G27915IV", "G84225JN", "G49108TO" ], "uniprot_id": "P22413" }, "relationship_type": "protective/causal", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation influences eNOS localization and activity.", "mechanism": "NOS3 variants affect NO production, regulating vasodilation and reducing vaso-occlusion.", "protein": "NOS3 (eNOS)", "relationship_type": "protective", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation impacts Golgi function and protein trafficking.", "mechanism": "GOLGB1 variant stabilizes Golgi structure, reducing platelet activation and stroke risk.", "protein": "GOLGB1", "protein_enriched": { "function": "May participate in forming intercisternal cross-bridges of the Golgi complex", "gene_name": "GOLGB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14789" }, "relationship_type": "protective", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "N-glycosylation modulates integrin activation and cell adhesion.", "mechanism": "ITGA4 variants enhance adhesion of sickled cells to endothelium, increasing stroke risk.", "protein": "ITGA4", "protein_enriched": { "function": "Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are al", "gene_name": "ITGA4", "glycan_count": 25, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G15664MX", "G23505EP", "G27058EU", "G31852PQ", "G41071NU", "G42124LM", "G43223CG", "G62765YT", "G80920RR", "G83460ZZ", "G90659AW", "G02815KT", "G11314AS", "G35253PZ", "G41247ZX", "G58087IP", "G81315DD", "G39471UU", "G76868JS", "G85554PZ", "G16125XL", "G82501QM", "G57776ZS", "G45395BF", "G63041LO" ], "uniprot_id": "P13612" }, "relationship_type": "causal", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation affects receptor stability and ligand binding.", "mechanism": "TGF\u03b2R-3 variants promote inflammatory signaling, increasing cerebral vasculopathy and stroke risk.", "protein": "TGF\u03b2R-3", "protein_enriched": { "function": "Cell surface receptor that regulates diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis (PubMed:12958365, PubMed:19416857). Initiates BMP, inhibin, and ", "gene_name": "TGFBR3", "glycan_count": 6, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G43417UB", "G70223PD", "G80920RR", "G99679NM", "G37692EO" ], "uniprot_id": "Q03167" }, "relationship_type": "causal", "source_pmcid": "PMC11203960" }, { "confidence": "medium", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "N-glycosylation modulates receptor signaling and immune cell interactions.", "mechanism": "IL4R variants increase endothelial adhesion and chronic inflammation, contributing to stroke risk.", "protein": "IL4R", "protein_enriched": { "function": "Receptor for both interleukin 4 and interleukin 13 (PubMed:17030238). Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are i", "gene_name": "IL4R", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22310AV", "G62765YT", "G88374WZ", "G80920RR" ], "uniprot_id": "P24394" }, "relationship_type": "causal", "source_pmcid": "PMC11203960" }, { "confidence": "low", "disease": "Stroke in Sickle Cell Disease", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "CBS variants reduce homocysteine levels, decreasing endothelial damage and stroke risk.", "protein": "CBS", "protein_enriched": { "function": "Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the p", "gene_name": "CBS", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P35520" }, "relationship_type": "protective", "source_pmcid": "PMC11203960" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies target native MOG, leading to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11204597" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may influence immune recognition.", "mechanism": "Autoantibodies (AQP4-IgG) target AQP4 on astrocytes, causing CNS inflammation and demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC11204597" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation may modulate immune response to MOG.", "mechanism": "Autoimmune responses to MOG observed in some MS patients; role less clear than in MOGAD.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker/possible causal", "source_pmcid": "PMC11204597" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Not directly discussed.", "mechanism": "AQP4-IgG is typically absent in MS, helping distinguish NMOSD from MS.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC11204597" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Not directly discussed.", "mechanism": "MOG-IgG is used to distinguish MOGAD from NMOSD (AQP4-IgG+).", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC11204597" }, { "confidence": "medium", "disease": "Healthy Population", "glycan_involvement": "Glycosylation may affect antibody binding and assay specificity.", "mechanism": "Low-level MOG-IgG can be found in healthy individuals; diagnostic cut-off required.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker (diagnostic threshold)", "source_pmcid": "PMC11204597" }, { "confidence": "medium", "disease": "Double-negative NMOSD", "glycan_involvement": "Not discussed.", "mechanism": "Absence of AQP4-IgG and MOG-IgG defines double-negative NMOSD; etiology unclear.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker (negative marker)", "source_pmcid": "PMC11204597" }, { "confidence": "medium", "disease": "Radiologically Isolated Syndrome (RIS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Presence of oligoclonal bands (including anti-MOG) in CSF is a risk factor for progression to MS.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker (risk stratification)", "source_pmcid": "PMC11204597" }, { "confidence": "medium", "disease": "Clinically Isolated Syndrome (CIS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Oligoclonal bands (possibly including anti-MOG) in CSF predict conversion to MS.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker (risk stratification)", "source_pmcid": "PMC11204597" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation may affect therapeutic antibody binding.", "mechanism": "AQP4 is targeted by monoclonal antibody therapies (e.g., eculizumab, inebilizumab) to prevent attacks.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204597" }, { "confidence": "high", "disease": "Combined central and peripheral demyelination (CCPD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "MOG-IgG antibodies associated with CNS demyelination and, rarely, PNS demyelination; mechanism unclear, possibly via molecular mimicry or low-level PNS expression.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition.", "mechanism": "MOG-IgG antibodies cause CNS demyelination (optic neuritis, myelitis, ADEM).", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "high", "disease": "Combined central and peripheral demyelination (CCPD)", "glycan_involvement": "NF155 is a glycoprotein; glycosylation critical for function and antibody recognition.", "mechanism": "Anti-NF155 antibodies target nodal/paranodal domains in both CNS and PNS, disrupting saltatory conduction.", "protein": "Neurofascin-155 (NF155)", "protein_enriched": { "function": "", "gene_name": "NRCAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92823-2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "medium", "disease": "Combined central and peripheral demyelination (CCPD)", "glycan_involvement": "MAG is highly glycosylated; sialic acid residues are key for function and autoantibody binding.", "mechanism": "Anti-MAG antibodies implicated in CCPD; MAG present at node of Ranvier in Schwann cells and oligodendrocytes.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may influence antibody binding.", "mechanism": "Anti-AQP4 antibodies cause astrocytopathy and secondary demyelination in NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "high", "disease": "Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)", "glycan_involvement": "Glycosylation of NF155 modulates immune recognition.", "mechanism": "Anti-NF155 antibodies found in subset of CIDP, associated with paranodal dysfunction.", "protein": "Neurofascin-155 (NF155)", "protein_enriched": { "function": "", "gene_name": "NRCAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92823-2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)", "glycan_involvement": "MAG glycosylation (sialic acid) is essential for antibody binding.", "mechanism": "Anti-MAG antibodies found in some CIDP cases, especially with distal demyelination.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)", "glycan_involvement": "MOG glycosylation may influence immune response.", "mechanism": "Rare cases of MOG-IgG seropositivity with CIDP-like demyelinating polyneuropathy; mechanism unclear.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker/causal (rare)", "source_pmcid": "PMC11204739" }, { "confidence": "medium", "disease": "Acute inflammatory demyelinating polyneuropathy (AIDP)", "glycan_involvement": "Glycosylation of NF155 is important for antibody interaction.", "mechanism": "Anti-NF155 antibodies found in some AIDP cases, affecting paranodal regions.", "protein": "Neurofascin-155 (NF155)", "protein_enriched": { "function": "", "gene_name": "NRCAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92823-2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MBP is not a glycoprotein; no glycan involvement.", "mechanism": "MBP is a major autoantigen in MS; T-cell and antibody responses implicated.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204739" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Thbs4 is a glycoprotein; glycosylation may affect secretion and ECM interactions.", "mechanism": "Overexpression mitigates dystrophic phenotype by enhancing trafficking of adhesion complexes to stabilize sarcolemma.", "protein": "Thrombospondin-4 (Thbs4)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the envir", "gene_name": "Map3k5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35099" }, "relationship_type": "protective", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 2F (LGMD2F)", "glycan_involvement": "Glycosylation may modulate Thbs4's ECM binding and trafficking functions.", "mechanism": "Overexpression mitigates disease; deletion exacerbates phenotype via effects on sarcolemma stability.", "protein": "Thrombospondin-4 (Thbs4)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the envir", "gene_name": "Map3k5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35099" }, "relationship_type": "protective", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 2E (LGMD2E)", "glycan_involvement": "Glycosylation status not directly linked to lack of effect.", "mechanism": "Deletion does not exacerbate disease; Thbs4 is upregulated but only extracellular, not affecting sarcolemma stability.", "protein": "Thrombospondin-4 (Thbs4)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the envir", "gene_name": "Map3k5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35099" }, "relationship_type": "not protective", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Glycosylation not directly implicated in mechanism.", "mechanism": "Deletion does not worsen phenotype; Thbs4 upregulated extracellularly, no effect on receptor trafficking.", "protein": "Thrombospondin-4 (Thbs4)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the envir", "gene_name": "Map3k5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35099" }, "relationship_type": "not protective", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 2E (LGMD2E)", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Genetic deficiency causes loss of DGC, leading to sarcolemma instability and muscular dystrophy.", "protein": "\u03b2-sarcoglycan", "protein_enriched": { "function": "This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Involved in autophagy in response to sta", "gene_name": "Atp2a2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O55143" }, "relationship_type": "causal", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 2F (LGMD2F)", "glycan_involvement": "Glycosylation important for DGC assembly.", "mechanism": "Genetic deficiency disrupts DGC, causing sarcolemma fragility and muscular dystrophy.", "protein": "\u03b4-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "Tlx3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O55144" }, "relationship_type": "causal", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Glycosylation critical for laminin-receptor interactions.", "mechanism": "Deficiency impairs ECM-receptor signaling, leading to muscle degeneration.", "protein": "Laminin \u03b12 chain", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "Lamb2", "glycan_count": 11, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G90659AW", "G06110VR", "G14994KB", "G29880MM", "G49874UX", "G59924QI", "G74724QE", "G84452RH", "G94854LT", "G49108TO" ], "uniprot_id": "Q61292" }, "relationship_type": "causal", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "O-glycosylation of \u03b1-dystroglycan essential for laminin binding.", "mechanism": "Acts as receptor for laminin \u03b12; loss of interaction contributes to pathology.", "protein": "Dystroglycan (\u03b1/\u03b2)", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "Dag1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43769HG", "G64527OM", "G49108TO", "G95177YH", "G57292HF", "G87015RU", "G80510PV" ], "uniprot_id": "Q62165" }, "relationship_type": "modulator", "source_pmcid": "PMC11208443" }, { "confidence": "medium", "disease": "LAMA2-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Glycosylation affects integrin function and localization.", "mechanism": "Loss of laminin \u03b12 impairs integrin signaling, contributing to muscle degeneration.", "protein": "Integrin \u03b17\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modulator", "source_pmcid": "PMC11208443" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation may influence Thbs4's ECM and cell interactions.", "mechanism": "Deletion exacerbates cardiomyopathy in DGC-deficient models by reducing membrane stability.", "protein": "Thrombospondin-4 (Thbs4)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the envir", "gene_name": "Map3k5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35099" }, "relationship_type": "protective", "source_pmcid": "PMC11208443" }, { "confidence": "high", "disease": "Enzootic bovine leukosis", "glycan_involvement": "gp51 is a glycoprotein; glycosylation required for function and immune recognition", "mechanism": "gp51 detected in exosomes from BLV-infected cattle; indicates infection", "protein": "BLV gp51 (Env)", "protein_enriched": { "function": "The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusoge", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P03374" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "B-cell lymphoma", "glycan_involvement": "glycosylation of gp51 modulates infectivity and immune evasion", "mechanism": "gp51 is essential for BLV entry and pathogenesis leading to lymphoma", "protein": "BLV gp51 (Env)", "protein_enriched": { "function": "The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusoge", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P03374" }, "relationship_type": "causal", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Persistent lymphocytosis", "glycan_involvement": "glycosylation affects gp51 immunogenicity", "mechanism": "gp51 presence in exosomes may contribute to immune modulation and lymphocyte proliferation", "protein": "BLV gp51 (Env)", "protein_enriched": { "function": "The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusoge", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P03374" }, "relationship_type": "causal", "source_pmcid": "PMC11210360" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "CD63 is a glycoprotein; glycosylation may affect exosome targeting", "mechanism": "CD63+ exosomes are significantly increased in melanoma patients", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "high", "disease": "Chronic hepatitis C", "glycan_involvement": "CD81 glycosylation modulates virus-receptor interaction", "mechanism": "CD81 is increased in serum of hepatitis C patients; involved in viral entry", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "glycosylation may influence exosome sorting and detection", "mechanism": "CD63 is suggested as a protein marker of cancer via exosomes", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "flotillin-1 is glycosylated; may affect membrane association", "mechanism": "Flotillin-1 is present in exosomes and involved in cell proliferation and invasion", "protein": "Flotillin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles", "gene_name": "FLOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O75955" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "glycosylation critical for MHC-II stability and function", "mechanism": "MHC-II in exosomes involved in antigen presentation and immune modulation", "protein": "MHC class II", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Enzootic bovine leukosis", "glycan_involvement": "glycosylation sites may be targeted for therapy", "mechanism": "gp51 in exosomes could be targeted for diagnostic or therapeutic intervention", "protein": "BLV gp51 (Env)", "protein_enriched": { "function": "The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusoge", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P03374" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210360" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "CD9 glycosylation may affect exosome formation and function", "mechanism": "CD9 is enriched in exosomes and associated with tumour progression", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210360" }, { "confidence": "high", "disease": "Down syndrome", "glycan_involvement": "Early decrease in galactosylation and sialylation, increase in fucosylation of Fc N-glycan.", "mechanism": "Altered IgG1 Fc glycosylation patterns (decreased galactosylation/sialylation, increased fucosylation) reflect premature aging in DS.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Premature aging", "glycan_involvement": "Age-dependent decrease in galactosylation/sialylation, increase in bisection.", "mechanism": "IgG1 Fc glycosylation patterns (galactosylation/sialylation decline, bisection increases) are associated with biological aging.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Respiratory tract infections", "glycan_involvement": "Reduced galactosylation/sialylation impairs complement activation; increased fucosylation decreases Fc\u03b3RIII binding.", "mechanism": "Altered IgG1 glycosylation in DS reduces antibody effector functions, increasing susceptibility to severe infections.", "protein": "IgG1", "relationship_type": "causal", "source_pmcid": "PMC11258452" }, { "confidence": "medium", "disease": "Autoimmunity", "glycan_involvement": "Premature aging signature in glycosylation may affect immune regulation.", "mechanism": "Altered IgG1 glycosylation in DS may contribute to increased autoimmunity prevalence.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "IgG1 glycosylation as a marker of biological aging.", "mechanism": "Premature aging in DS, reflected in IgG1 glycosylation, is associated with early onset Alzheimer's.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Down syndrome", "glycan_involvement": "Glycosylation profile affects vaccine-induced antibody function.", "mechanism": "Altered IgG1 glycosylation suggests need for tailored vaccine regimens in DS.", "protein": "IgG1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11258452" }, { "confidence": "medium", "disease": "Respiratory tract infections", "glycan_involvement": "Increased fucosylation decreases Fc\u03b3RIII-mediated cytokine production.", "mechanism": "High fucosylation in DS may reduce excessive immune activation, potentially protective against hyperinflammation.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Down syndrome", "glycan_involvement": "Galactosylation/sialylation levels in DS match those of HC 28\u201336 years older.", "mechanism": "IgG1 glycosylation profile in DS resembles that of much older healthy controls, indicating accelerated immune aging.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Premature aging", "glycan_involvement": "Age-dependent glycan trait changes.", "mechanism": "IgG1 glycosylation changes (decreased galactosylation/sialylation) are established markers of immunosenescence.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Down syndrome", "glycan_involvement": "Altered glycosylation and lower antibody titers.", "mechanism": "IgG1 glycosylation alterations combined with decreased antibody concentrations explain increased infection susceptibility in DS.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11258452" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Defective glycosylation of \u03b1-DG is central to disease mechanism.", "mechanism": "Variants in DAG1 or glycosylation enzymes impair \u03b1-DG glycosylation, disrupting extracellular matrix linkage and causing muscular dystrophy.", "protein": "\u03b1-dystroglycan (DG)", "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease", "glycan_involvement": "Altered glycosylation of \u03b1-DG impacts tissue barriers.", "mechanism": "C667F variant in DAG1 affects \u03b1-DG glycosylation, leading to myopathy with altered blood\u2013brain and blood\u2013retina barrier protein composition.", "protein": "\u03b1-dystroglycan (DG)", "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "medium", "disease": "Dystroglycanopathy", "glycan_involvement": "Glycosylation status affects \u03b2-DG function.", "mechanism": "Variants in DAG1 affect \u03b2-DG, disrupting cytoskeleton\u2013ECM linkage.", "protein": "\u03b2-dystroglycan (DG)", "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential glycosylation modulates annexin A6 function.", "mechanism": "Annexin A6 addition improves cardiac myocyte phenotype in DMD iPSC models.", "protein": "Annexin A6", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "ANXA6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08133" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11261626" }, { "confidence": "medium", "disease": "Snyder\u2013Robinson Syndrome (SRS)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Mutations in spermine synthase disrupt polyamine metabolism, causing SRS symptoms.", "protein": "Spermine synthase", "protein_enriched": { "function": "Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport (PubMed:15510212, PubMed", "gene_name": "SLC17A5", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9NRA2" }, "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "medium", "disease": "Robinow syndrome", "glycan_involvement": "Glycosylation may affect FZD2 receptor function.", "mechanism": "Missense variants in FZD2 impair Wnt signaling and craniofacial morphogenesis.", "protein": "FZD2", "protein_enriched": { "function": "Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuc", "gene_name": "FZD2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G28905MY", "G53434XO", "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q14332" }, "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "low", "disease": "TANGO2 deficiency disorder (TDD)", "glycan_involvement": "Potential glycosylation affects TANGO2 trafficking/function.", "mechanism": "Loss-of-function variants in TANGO2 cause metabolic crises.", "protein": "TANGO2", "protein_enriched": { "function": "Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates t", "gene_name": "CC2D1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6P1N0" }, "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "low", "disease": "CAMRQ4", "glycan_involvement": "Potential glycosylation may affect membrane localization.", "mechanism": "Variants in ATP8A2 cause cerebellar ataxia and intellectual disability.", "protein": "ATP8A2", "protein_enriched": { "function": "Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "ATP8A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NTI2" }, "relationship_type": "causal", "source_pmcid": "PMC11261626" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease", "glycan_involvement": "Glycosylation status is diagnostic.", "mechanism": "Altered glycosylation of \u03b1-DG can be used to diagnose muscle\u2013eye\u2013brain disease.", "protein": "\u03b1-dystroglycan (DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11261626" }, { "confidence": "medium", "disease": "Muscle\u2013eye\u2013brain disease", "glycan_involvement": "Glycosylation may modulate barrier function.", "mechanism": "Protein composition changes in blood\u2013brain and blood\u2013retina barrier involve \u03b2-DG.", "protein": "\u03b2-dystroglycan (DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11261626" }, { "confidence": "high", "disease": "SSR4-CDG", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins due to impaired ER translocation.", "mechanism": "Loss-of-function SSR4 variant impairs TRAP complex, reducing N-glycosylation efficiency and causing multi-organ dysfunction.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "high", "disease": "Developmental delay", "glycan_involvement": "N-glycosylation defects disrupt neuronal glycoprotein maturation.", "mechanism": "Impaired glycosylation affects neurodevelopmental pathways.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "medium", "disease": "Coagulation disorder", "glycan_involvement": "N-glycosylation defects in coagulation glycoproteins.", "mechanism": "Aberrant glycosylation impacts coagulation factor function.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "medium", "disease": "Hypotonia", "glycan_involvement": "N-glycosylation defects in muscle-associated glycoproteins.", "mechanism": "Defective glycosylation impairs muscle contraction and regulation.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "medium", "disease": "Feeding difficulty", "glycan_involvement": "N-glycosylation impacts GI tract glycoproteins.", "mechanism": "Glycosylation defects affect gastrointestinal function.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "high", "disease": "CDG (general)", "glycan_involvement": "Abnormal N-glycosylation pattern detected by isoelectric focusing.", "mechanism": "Altered transferrin glycoforms used for CDG screening.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11288868" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation of serum and cellular glycoproteins.", "mechanism": "PMM2 mutations impair N-glycosylation precursor synthesis.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC11288868" }, { "confidence": "high", "disease": "Dystrophin-deficient muscular dystrophy", "glycan_involvement": "Dystrophin interacts with glycosylated dystroglycans; loss affects glycoprotein complex stability.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex, causing membrane instability and muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "Merosin-deficient muscular dystrophy", "glycan_involvement": "Laminin is heavily glycosylated; glycosylation is critical for its function in ECM.", "mechanism": "Deficiency impairs muscle basement membrane integrity, leading to muscle degeneration.", "protein": "Laminin alpha 2 (Merosin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "Sarcoglycan-deficient muscular dystrophy", "glycan_involvement": "Sarcoglycans are glycosylated; glycosylation affects complex assembly.", "mechanism": "Loss of sarcoglycan disrupts the sarcoglycan complex, weakening muscle membrane.", "protein": "Alpha-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "Sarcoglycan-deficient muscular dystrophy", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Deficiency leads to sarcoglycan complex instability and muscle degeneration.", "protein": "Beta-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "Sarcoglycan-deficient muscular dystrophy", "glycan_involvement": "Glycosylation modulates protein-protein interactions.", "mechanism": "Loss impairs sarcoglycan complex, causing muscle weakness.", "protein": "Gamma-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "Muscular dystrophy (MD)", "glycan_involvement": "O-mannosyl glycosylation is essential for laminin binding.", "mechanism": "Defective glycosylation of alpha-dystroglycan impairs ECM binding, leading to MD.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "medium", "disease": "Muscular dystrophy (MD)", "glycan_involvement": "Glycosylation required for proper complex formation.", "mechanism": "Loss affects dystrophin-glycoprotein complex, destabilizing muscle membrane.", "protein": "Beta-dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "medium", "disease": "Muscular dystrophy (MD)", "glycan_involvement": "Glycosylation may affect membrane localization.", "mechanism": "Upregulation can partially compensate for dystrophin loss.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC11297512" }, { "confidence": "medium", "disease": "Muscular dystrophy (MD)", "glycan_involvement": "Glycosylation modulates membrane repair function.", "mechanism": "Deficiency impairs membrane repair, exacerbating muscle degeneration.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "medium", "disease": "Lingual hypertrophy (macroglossia)", "glycan_involvement": "Glycosylation critical for ECM interactions.", "mechanism": "Deficiency can cause muscle hypertrophy including tongue.", "protein": "Laminin alpha 2 (Merosin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11297512" }, { "confidence": "high", "disease": "LGMD2I/R9", "glycan_involvement": "Defective O-mannosyl matriglycan synthesis on \u03b1DG", "mechanism": "Mutations in FKRP cause defective glycosylation of \u03b1DG, impairing its ability to bind extracellular matrix and destabilizing muscle membrane.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "causal", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Loss or reduction of matriglycan O-glycan structures", "mechanism": "Aberrant glycosylation of \u03b1DG leads to failure of myocyte attachment to basal membrane, causing contraction-induced injury.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "causal", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "LGMD2I/R9", "glycan_involvement": "Quantitative reduction and hypoglycosylation of matriglycan on \u03b1DG", "mechanism": "Levels and glycosylation status of \u03b1DG in muscle biopsies reflect disease severity and response to therapy.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "Muscular dystrophy (general)", "glycan_involvement": "Impaired O-mannosylation and matriglycan formation", "mechanism": "Defective glycosylation of \u03b1DG disrupts cytoskeleton-extracellular matrix linkage, leading to muscle degeneration.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "causal", "source_pmcid": "PMC11316722" }, { "confidence": "medium", "disease": "Nervous system disorders (secondary to dystroglycanopathy)", "glycan_involvement": "Reduced matriglycan O-glycan modification", "mechanism": "Defective glycosylation of \u03b1DG affects brain and nervous system development/function.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "causal", "source_pmcid": "PMC11316722" }, { "confidence": "medium", "disease": "LGMD2I/R9", "glycan_involvement": "Therapeutic increase of matriglycan O-glycosylation", "mechanism": "Restoration of \u03b1DG glycosylation (e.g., via ribitol supplementation) can improve muscle function.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "LGMD2I/R9", "glycan_involvement": "Detection of matriglycan O-glycan epitope", "mechanism": "IIH6C4 antibody reactivity to matriglycan on \u03b1DG serves as a functional biomarker for disease monitoring.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11316722" }, { "confidence": "medium", "disease": "LGMD2I/R9", "glycan_involvement": "Extent of matriglycan O-glycan deficiency", "mechanism": "Degree of \u03b1DG hypoglycosylation correlates with clinical severity in some FKRP genotypes.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "LGMD2I/R9", "glycan_involvement": "Pattern and level of matriglycan O-glycosylation", "mechanism": "Western blot quantification of glycosylated \u03b1DG distinguishes between L276I homozygous and compound heterozygous FKRP mutations.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11316722" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Loss of functional O-mannosyl matriglycan", "mechanism": "Reduced matriglycan-modified \u03b1DG is a diagnostic marker for dystroglycanopathies.", "protein": "Alpha-dystroglycan (\u03b1DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11316722" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Sialylation enhances fetuin's interaction with insulin receptor, modulating glucose metabolism.", "mechanism": "Sialylated fetuin binds insulin receptor \u03b2-subunit, attenuating insulin signaling and reducing glucose uptake.", "protein": "Fetuin", "relationship_type": "causal", "source_pmcid": "PMC11331314" }, { "confidence": "low", "disease": "Bone mineralization disorders", "glycan_involvement": "Sialylation stabilizes fetuin structure, potentially affecting its mineral-binding properties.", "mechanism": "Fetuin regulates bone mineralization; sialylation may modulate this function.", "protein": "Fetuin", "relationship_type": "protective", "source_pmcid": "PMC11331314" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Sialylation stabilizes fetuin and may affect immune modulation.", "mechanism": "Fetuin modulates immune responses; sialylation may influence its anti-inflammatory properties.", "protein": "Fetuin", "relationship_type": "modulatory", "source_pmcid": "PMC11331314" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Fc sialylation modulates immune receptor binding.", "mechanism": "Sialylation of IgG Fc region increases affinity for inhibitory Fc\u03b3RIIB, promoting anti-inflammatory effects.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11331314" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Sialylation status reflects disease state.", "mechanism": "Altered sialylation patterns of fetuin are implicated in cancer biology and may serve as biomarkers.", "protein": "Fetuin", "relationship_type": "biomarker", "source_pmcid": "PMC11331314" }, { "confidence": "high", "disease": "Biomarker for glycosylation disorders", "glycan_involvement": "Differential sialylation stabilizes transferrin conformation.", "mechanism": "Sialylation status of transferrin is used to diagnose glycosylation disorders.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11331314" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans and sialylation affect spike-ACE2 interaction.", "mechanism": "Spike protein glycosylation, including sialylation, modulates ACE2 binding and viral entry.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11331314" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans and sialylation modulate receptor function.", "mechanism": "ACE2 glycosylation, including sialylation, influences spike protein binding and infection susceptibility.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC11331314" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Sialylation status as a marker of metabolic dysfunction.", "mechanism": "Sialylated fetuin levels correlate with metabolic syndrome features.", "protein": "Fetuin", "relationship_type": "biomarker", "source_pmcid": "PMC11331314" }, { "confidence": "low", "disease": "Immune modulation", "glycan_involvement": "Sialylation modulates cell\u2013cell recognition and immune response.", "mechanism": "Sialylation affects fetuin's role in immune cell interactions.", "protein": "Fetuin", "relationship_type": "modulatory", "source_pmcid": "PMC11331314" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APP processing and amyloid-beta generation.", "mechanism": "APP mutations and abnormal processing lead to amyloid-beta aggregation and plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "CD44 glycosylation modulates cell adhesion and immune response.", "mechanism": "Altered CSF levels correlate with Parkinson's disease severity.", "protein": "Cluster of differentiation 44 (CD44)", "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Involved in glycan catabolism, impacting glycoprotein turnover.", "mechanism": "CSF levels altered in Parkinson's disease patients.", "protein": "Mannosidase alpha class 2B member 1 (MAN2B1)", "protein_enriched": { "function": "Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages", "gene_name": "MAN2B1", "glycan_count": 63, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G08290VR", "G45395BF", "G47644PP", "G92275SC", "G02815KT", "G28681TP", "G41247ZX", "G05724UK", "G06110VR", "G14669DU", "G31852PQ", "G39188ZX", "G46691LC", "G50282JC", "G62765YT", "G80920RR", "G82443XX", "G83460ZZ", "G90575OW", "G49108TO", "G77277QT", "G00912UN", "G01485JJ", "G02886BB", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G35029YA", "G41071NU", "G42124LM", "G48414YA", "G49955PK", "G57317CE", "G57776ZU", "G59626AS", "G65184UU", "G72291OX", "G72787SB", "G72790NZ", "G85269DF", "G90734RJ", "G92050GC", "G95865ZB", "G01650EU", "G05049YU", "G11314AS", "G11870QZ", "G12313PD", "G27058EU", "G29299MO", "G37399XV", "G47950XN", "G55383ZG", "G62894KT", "G74724QE", "G82463GQ", "G28541PG", "G25637MV", "G63041LO", "G84349RE", "G90659AW", "G96091TT" ], "uniprot_id": "O00754" }, "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation modulates aggregation propensity and toxicity.", "mechanism": "Aggregation of alpha-synuclein leads to Lewy body formation and neurodegeneration.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Associated with neuroinflammation and immune response in advanced Parkinson's disease.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Altered CSF levels in Parkinson's disease.", "protein": "Osteomodulin", "protein_enriched": { "function": "May be implicated in biomineralization processes. Has a function in binding of osteoblasts via the alpha(V)beta(3)-integrin", "gene_name": "OMD", "glycan_count": 8, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G29580WD", "G90787TS", "G00912UN", "G06356OH", "G31028YV", "G37509XX", "G48414YA", "G69521XL" ], "uniprot_id": "Q99983" }, "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation modulates hormone stability and receptor binding.", "mechanism": "CSF levels altered in Parkinson's disease.", "protein": "Prolactin", "protein_enriched": { "function": "Prolactin acts primarily on the mammary gland by promoting lactation", "gene_name": "PRL", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01236" }, "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects secretion and neurotrophic activity.", "mechanism": "CSF levels altered in Parkinson's disease.", "protein": "VGF nerve growth factor inducible", "protein_enriched": { "function": "Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner (By similarity). VGF and peptides derived from its processi", "gene_name": "VGF", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "O15240" }, "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation critical for antigen presentation and immune modulation.", "mechanism": "Increased CSF levels indicate elevated neuroinflammation in LRRK2 G2019S carriers.", "protein": "Human leukocyte antigen (HLA)", "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Glycosylation affects APP trafficking and function.", "mechanism": "Altered APP processing and glycosylation may contribute to neurodevelopmental changes.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC11334939" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Isoform-specific O-glycosylation and sialylation modulate ApoE-A\u03b2 interaction and pathogenesis; higher sialylation (ApoE2) is protective.", "mechanism": "ApoE isoforms differentially modulate amyloid \u03b2 (A\u03b2) accumulation, tau phosphorylation, neuroinflammation, and glucose metabolism; ApoE4 confers greatest risk, ApoE2 is protective.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Type III hyperlipoproteinemia", "glycan_involvement": "Glycosylation at hinge and C-terminal regions may influence lipoprotein binding and metabolism.", "mechanism": "ApoE2 defective binding to LDL receptor leads to LDL accumulation; rare variants (e.g., R145C) increase risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Sialylation status affects ApoE binding to HDL/VLDL and cholesterol transport.", "mechanism": "ApoE4 upregulates plasma VLDL, impairs clearance, increases atherogenic profile.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Altered O-glycosylation at Ser129 may serve as a biomarker.", "mechanism": "Increased glycosylation at Ser129 in plasma ApoE observed in stage II breast cancer patients.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Sialylation enhances HDL binding and cholesterol efflux; desialylation impairs function.", "mechanism": "ApoE glycosylation and sialylation modulate lipid metabolism and reverse cholesterol transport.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "low", "disease": "Gynecological diseases", "glycan_involvement": "Changes in O-glycosylation may reflect disease status.", "mechanism": "Altered ApoE glycosylation patterns observed in gynecological disease states.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC11335735" }, { "confidence": "low", "disease": "Coronary heart disease", "glycan_involvement": "Glycosylation in lipid-binding region may affect lipid metabolism.", "mechanism": "Rare ApoE variants (e.g., R251G) linked to lipid dysmetabolism and increased coronary risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Potential modulation of glycosylation/sialylation at key sites may contribute to protective effects.", "mechanism": "Rare ApoE variants (Christchurch, V236E, R251G) reduce AD risk by altering receptor/lipid binding and aggregation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Mutations may alter glycosylation patterns, impacting protein structure and disease susceptibility.", "mechanism": "ApoE4-L28P and ApoE3-R145C variants increase AD risk, especially in specific populations.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11335735" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation in receptor-binding region modulates HSPG interaction.", "mechanism": "Antibody (7C11) targeting ApoE4-HSPG interaction reduces cytotoxicity and tau phosphorylation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11335735" }, { "confidence": "high", "disease": "Sialidosis", "glycan_involvement": "Impaired degradation of sialylated glycoproteins (N- and O-linked).", "mechanism": "NEU1 deficiency leads to accumulation of sialylated glycoproteins in lysosomes.", "protein": "NEU1", "protein_enriched": { "function": "Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears t", "gene_name": "NEU1", "glycan_count": 32, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10486CT", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G35029YA", "G37995HC", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G49642SA", "G49955PK", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G72787SB", "G72790NZ", "G83646BJ", "G85282JO", "G87661QW", "G90659AW", "G92275SC", "G95177YH", "G15664MX", "G80920RR", "G49108TO" ], "uniprot_id": "Q99519" }, "relationship_type": "causal", "source_pmcid": "PMC11353077" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Desialylation of APP alters aggregation and clearance.", "mechanism": "NEU1 regulates APP desialylation, affecting amyloid plaque formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11353077" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Desialylation of N-glycans on CD36 modulates receptor activity.", "mechanism": "NEU1 desialylates CD36, enhancing oxLDL uptake and foam cell formation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11353077" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Desialylation of N-glycans on EGFR enhances signaling.", "mechanism": "NEU1 removes sialic acids from EGFR, promoting dimerization and pro-survival signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11353077" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "Desialylation of N-glycans on IR increases receptor activation.", "mechanism": "NEU1 desialylates IR, facilitating dimerization and insulin signaling.", "protein": "Insulin Receptor (IR)", "protein_enriched": { "function": "Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS", "gene_name": "INSR", "glycan_count": 83, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G80920RR", "G11101UV", "G31852PQ", "G56014GC", "G62765YT", "G72951AH", "G81315DD", "G83460ZZ", "G02815KT", "G05049YU", "G10486CT", "G15664MX", "G41247ZX", "G55220VL", "G64527OM", "G72747WU", "G90659AW", "G92406TI", "G00395TQ", "G00912UN", "G07246CJ", "G07483YN", "G08918WF", "G14972EH", "G27058EU", "G41071NU", "G42466VF", "G45395BF", "G47644PP", "G59626AS", "G83646BJ", "G87661QW", "G04657PL", "G05962QB", "G12341GU", "G20312EM", "G39203UC", "G57776ZS", "G60834IK", "G70232NH", "G77582RK", "G80075MS", "G10819WX", "G13131HA", "G16125XL", "G20706XG", "G27947YN", "G29545VG", "G35541EV", "G37818NZ", "G39471UU", "G40926MX", "G43223CG", "G49755GI", "G49906RN", "G55132BD", "G58087IP", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G81263BG", "G85282JO", "G86880BF", "G87123QX", "G93718GY", "G96577RX", "G05724UK", "G20528HD", "G07755XJ", "G54010QB", "G50303LH", "G29068FM", "G43417UB", "G58001LT", "G01650EU", "G23294PN", "G23984SE", "G28541PG", "G37399XV", "G70223PD", "G95865ZB" ], "uniprot_id": "P06213" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11353077" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis", "glycan_involvement": "Desialylation of O-glycans on MUC1 affects mucin function.", "mechanism": "NEU1-mediated desialylation of MUC1 promotes shedding and inflammation.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11353077" }, { "confidence": "medium", "disease": "Colon Cancer", "glycan_involvement": "Reduced sialylation of N-glycans on integrin \u03b24 decreases cell motility.", "mechanism": "NEU1 overexpression reduces \u03b24-integrin sialylation, inhibiting migration and invasion.", "protein": "Integrin \u03b24", "protein_enriched": { "function": "Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA", "gene_name": "ITGB4", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G13131HA", "G14972EH", "G27058EU", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G62765YT", "G70619PT", "G80920RR", "G85282JO", "G87661QW", "G90382BL", "G92135MA", "G98611JV" ], "uniprot_id": "P16144" }, "relationship_type": "protective", "source_pmcid": "PMC11353077" }, { "confidence": "medium", "disease": "Renal Fibrosis", "glycan_involvement": "Likely involves altered glycosylation of ALK5 and related receptors.", "mechanism": "NEU1 upregulation stabilizes ALK5, activating SMAD2/3 and promoting fibrosis.", "protein": "NEU1", "protein_enriched": { "function": "Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears t", "gene_name": "NEU1", "glycan_count": 32, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10486CT", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G35029YA", "G37995HC", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G49642SA", "G49955PK", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G72787SB", "G72790NZ", "G83646BJ", "G85282JO", "G87661QW", "G90659AW", "G92275SC", "G95177YH", "G15664MX", "G80920RR", "G49108TO" ], "uniprot_id": "Q99519" }, "relationship_type": "causal", "source_pmcid": "PMC11353077" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Desialylation of integrin glycoproteins dampens Akt pathway activation.", "mechanism": "NEU1 overexpression inhibits fibronectin/integrin \u03b15\u03b21 signaling, reducing tumor growth.", "protein": "Fibronectin/integrin \u03b15\u03b21", "relationship_type": "protective", "source_pmcid": "PMC11353077" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Altered sialylation of cell-surface glycoproteins modulates oncogenic pathways.", "mechanism": "High NEU1 expression correlates with poor prognosis and increased proliferation.", "protein": "NEU1", "protein_enriched": { "function": "Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears t", "gene_name": "NEU1", "glycan_count": 32, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10486CT", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G35029YA", "G37995HC", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G49642SA", "G49955PK", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G72787SB", "G72790NZ", "G83646BJ", "G85282JO", "G87661QW", "G90659AW", "G92275SC", "G95177YH", "G15664MX", "G80920RR", "G49108TO" ], "uniprot_id": "Q99519" }, "relationship_type": "biomarker", "source_pmcid": "PMC11353077" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (Type II)", "glycan_involvement": "Defective O-linked glycosylation of \u03b1-dystroglycan impairs neuronal migration.", "mechanism": "Mutations disrupt O-mannosylation of proteins critical for neuronal migration and basement membrane integrity.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (Type II)", "glycan_involvement": "Loss of O-linked glycosylation on \u03b1-dystroglycan disrupts cortical development.", "mechanism": "Mutations impair O-mannosylation, leading to breaches in the pial basement membrane and overmigration of neurons.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Muscle-Eye-Brain disease (MEB)", "glycan_involvement": "Impaired O-linked glycosylation of \u03b1-dystroglycan leads to neuronal and muscular defects.", "mechanism": "Mutations cause defective O-mannosyl glycan extension, affecting brain and muscle development.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Defective O-linked glycosylation impairs basement membrane integrity.", "mechanism": "Mutations disrupt glycosylation of \u03b1-dystroglycan, affecting muscle and brain structure.", "protein": "Fukutin", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio", "gene_name": "TUBB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G47950XN" ], "uniprot_id": "Q9H4B7" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (Type II)", "glycan_involvement": "O-linked glycosylation defect disrupts cortical and muscular development.", "mechanism": "Mutations impair glycosylation of \u03b1-dystroglycan, leading to neuronal migration defects.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Loss of O-linked glycosylation on \u03b1-dystroglycan.", "mechanism": "Mutations cause severe disruption of O-mannosylation, leading to brain, eye, and muscle anomalies.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective O-linked glycosylation of \u03b1-dystroglycan.", "mechanism": "Mutations result in defective O-mannosylation, causing cobblestone cortex and muscular dystrophy.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (Type II)", "glycan_involvement": "O-linked glycosylation defect affects brain development.", "mechanism": "Mutations impair glycan extension on \u03b1-dystroglycan, leading to neuronal migration defects.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (Type II)", "glycan_involvement": "O-linked glycosylation defect impairs neuronal migration.", "mechanism": "Mutations disrupt glycosylation of \u03b1-dystroglycan, causing brain malformations.", "protein": "Fukutin", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio", "gene_name": "TUBB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G47950XN" ], "uniprot_id": "Q9H4B7" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Defective O-linked glycosylation disrupts basement membrane and neuronal migration.", "mechanism": "Mutations impair glycosylation of \u03b1-dystroglycan, leading to muscular and brain abnormalities.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11367506" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "O-mannosylation is disrupted, leading to loss of ligand binding and abnormal neuronal migration.", "mechanism": "Defective glycosylation of alpha-dystroglycan impairs its function in muscle and brain development.", "protein": "alpha-dystroglycan", "protein_enriched": { "function": "Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immu", "gene_name": "LAT", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O43561" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Impaired addition of xylose to O-mannosyl glycans on alpha-dystroglycan.", "mechanism": "Mutations in TMEM5 impair its glycosyltransferase activity, leading to defective glycosylation of alpha-dystroglycan.", "protein": "TMEM5 (RXYLT1)", "protein_enriched": { "function": "Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics ", "gene_name": "ENAH", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85269DF", "G49108TO", "G80920RR", "G80770LV" ], "uniprot_id": "Q8N8S7" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Loss of initial mannose addition to alpha-dystroglycan O-glycans.", "mechanism": "POMT1 mutations disrupt O-mannosylation of alpha-dystroglycan.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Loss of initial mannose addition to alpha-dystroglycan O-glycans.", "mechanism": "POMT2 mutations disrupt O-mannosylation of alpha-dystroglycan.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "medium", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective glycan maturation on alpha-dystroglycan O-mannosylation pathway.", "mechanism": "FKRP mutations impair further glycan extension on alpha-dystroglycan.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "medium", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective glycan maturation on alpha-dystroglycan O-mannosylation pathway.", "mechanism": "FKTN mutations impair glycan extension on alpha-dystroglycan.", "protein": "FKTN", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis", "gene_name": "CTSF", "glycan_count": 21, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G27058EU", "G41071NU", "G45395BF", "G58954YZ", "G62765YT", "G72667IM", "G75983OB", "G80920RR", "G83460ZZ", "G92050GC", "G92275SC", "G02815KT", "G23505EP", "G27126ED", "G28681TP", "G31852PQ", "G39188ZX", "G41247ZX", "G73430PD", "G80510PV" ], "uniprot_id": "Q9UBX1" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "medium", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective addition of repeating disaccharide units to O-mannosyl glycans.", "mechanism": "LARGE mutations impair glycan polymerization on alpha-dystroglycan.", "protein": "LARGE", "protein_enriched": { "function": "Probable metal transporter", "gene_name": "CNNM1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G80920RR" ], "uniprot_id": "Q9NRU3" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "medium", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Defective O-mannosyl glycan branching on alpha-dystroglycan.", "mechanism": "POMGNT1 mutations impair N-acetylglucosamine addition to O-mannosyl glycans on alpha-dystroglycan.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Cobblestone lissencephaly", "glycan_involvement": "Loss of O-mannosyl glycan-mediated interactions with extracellular matrix.", "mechanism": "Hypoglycosylated alpha-dystroglycan fails to maintain basement membrane integrity, leading to abnormal neuronal migration.", "protein": "alpha-dystroglycan", "protein_enriched": { "function": "Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immu", "gene_name": "LAT", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O43561" }, "relationship_type": "causal", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Congenital muscular dystrophy-dystroglycanopathy (type A10)", "glycan_involvement": "Defective O-mannosylation detected by immunohistochemistry or biochemical assays.", "mechanism": "Abnormal glycosylation of alpha-dystroglycan is diagnostic for dystroglycanopathies.", "protein": "alpha-dystroglycan", "protein_enriched": { "function": "Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immu", "gene_name": "LAT", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O43561" }, "relationship_type": "biomarker", "source_pmcid": "PMC11381981" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Defective N-glycosylation impairs folding and trafficking, leading to ER retention.", "mechanism": "Loss-of-function SLC6A1 mutations impair GAT1 folding/trafficking, reducing GABA uptake and disrupting inhibitory neurotransmission.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "SLC6A1 mutations reduce GAT1 activity, affecting GABAergic signaling critical for cognitive development.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Autism spectrum disorder", "glycan_involvement": "Glycosylation defects impair trafficking and function.", "mechanism": "SLC6A1 mutations disrupt GABAergic neurotransmission, contributing to ASD phenotypes.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "high", "disease": "Creatine transporter deficiency syndrome", "glycan_involvement": "N-glycosylation essential for CRT1 maturation and trafficking.", "mechanism": "Folding-deficient CRT1 mutants are retained in the ER due to glycosylation/trafficking defects.", "protein": "Creatine transporter 1 (CRT1)", "protein_enriched": { "function": "Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1. Functions as amino acid antip", "gene_name": "SLC7A8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UHI5" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Infantile parkinsonism", "glycan_involvement": "N-glycosylation and chaperone interactions affect folding and ER export.", "mechanism": "Misfolded DAT variants are retained in the ER, reducing dopamine reuptake.", "protein": "Dopamine transporter (DAT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, Pu", "gene_name": "SLC6A3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q01959" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Neurological disorder", "glycan_involvement": "N-glycosylation and chaperone binding regulate folding and trafficking.", "mechanism": "Folding-deficient SERT mutants are retained in the ER, impairing serotonin uptake.", "protein": "Serotonin transporter (SERT)", "protein_enriched": { "function": "Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the ", "gene_name": "SLC6A4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31645" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Indirect; syntaxin-1A regulates glycoprotein trafficking.", "mechanism": "Missense mutations in syntaxin-1A gene disrupt GAT1 trafficking and GABA release.", "protein": "Syntaxin-1A", "protein_enriched": { "function": "Potentially involved in docking of synaptic vesicles at presynaptic active zones. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm (By similarity)", "gene_name": "STX1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61266" }, "relationship_type": "causal", "source_pmcid": "PMC11390516" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Chemical chaperones improve folding and glycosylation status.", "mechanism": "Pharmacochaperones (e.g., 4-PBA, tiagabine) rescue misfolded GAT1 variants, restoring surface expression and function.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation status affects detectability and function.", "mechanism": "Surface expression and function of GAT1 correlate with disease severity and response to therapy.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "biomarker", "source_pmcid": "PMC11390516" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation required for proper localization in thalamus.", "mechanism": "Deep brain stimulation targeting thalamic GAT1 may reduce refractory seizures.", "protein": "GABA transporter 1 (GAT1)", "protein_enriched": { "function": "Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, howeve", "gene_name": "SLC6A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30531" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11390516" }, { "confidence": "high", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Increased sialic acid residues on glycoproteins mask tumor antigens and disrupt cell-cell interactions.", "mechanism": "Hypersialylation promotes immune evasion, tumor invasion, and metastasis.", "protein": "Sialylated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11391619" }, { "confidence": "medium", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Sialylation of Fas receptor prevents apoptotic cell death.", "mechanism": "Sialylation blocks Fas receptor, impeding apoptosis signaling.", "protein": "Fas receptor", "protein_enriched": { "function": "Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 proteolytic activation which", "gene_name": "FAS", "glycan_count": 32, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08290VR", "G08918WF", "G14972EH", "G23719VF", "G27058EU", "G37995HC", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G80075MS", "G83460ZZ", "G83646BJ", "G85282JO", "G86182NS", "G87661QW", "G90659AW", "G95177YH", "G83633GK", "G43417UB", "G57321FI", "G29931IJ", "G57317CE", "G29068FM" ], "uniprot_id": "P25445" }, "relationship_type": "protective (when unsialylated)", "source_pmcid": "PMC11391619" }, { "confidence": "medium", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Sialylation of TNF receptor prevents apoptotic cell death.", "mechanism": "Sialylation blocks TNF receptor, impeding apoptosis signaling.", "protein": "TNF receptor", "protein_enriched": { "function": "Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) p", "gene_name": "TNFRSF1A", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "P19438" }, "relationship_type": "protective (when unsialylated)", "source_pmcid": "PMC11391619" }, { "confidence": "high", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Enzymatic addition of sialic acids to glycoproteins.", "mechanism": "Upregulation leads to hypersialylation and cancer progression.", "protein": "Sialyltransferases", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11391619" }, { "confidence": "medium", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Glycosylation modulates immune checkpoint function.", "mechanism": "Elevated CD200 suppresses immune activity, promoting tumor growth.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11391619" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation may affect ligand-receptor interactions.", "mechanism": "High TNFSF9 expression linked to anti-tumor activity and improved survival.", "protein": "TNFSF9 (CD137L)", "protein_enriched": { "function": "Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis", "gene_name": "TNFSF15", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O95150" }, "relationship_type": "protective", "source_pmcid": "PMC11391619" }, { "confidence": "high", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Glycosylation of checkpoint proteins influences their function and immune evasion.", "mechanism": "Immune checkpoint inhibitors can reactivate immune response against sialylated tumors.", "protein": "PD-1/PD-L1/CTLA-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11391619" }, { "confidence": "high", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Altered glycosylation patterns regulated by lncRNAs.", "mechanism": "lncRNAs co-expressed with sialylation genes predict prognosis and treatment response.", "protein": "Sialylated lncRNA-associated glycoproteins", "relationship_type": "biomarker", 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"source_pmcid": "PMC11399422" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Decreased sialylation of N-glycans.", "mechanism": "Lower sialylation of IgG N-glycans associated with increased CAD risk, especially in women.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11399422" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Increased bisecting GlcNAc.", "mechanism": "Increased bisecting GlcNAc in IgG N-glycans correlates with plaque presence.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11399422" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus", "glycan_involvement": "Increased high-mannose, bisecting GlcNAc, disialylation; decreased monogalactosylation.", "mechanism": "Increased high-mannose, bisecting GlcNAc, disialylation; decreased monogalactosylation associated with T1DM onset.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11399422" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Increased sialylation (IgG4), increased digalactosylation (IgG2), decreased agalactosylation (IgG4), decreased bisecting GlcNAc (IgG2).", "mechanism": "Altered IgG glycosylation (increased sialylation of IgG4, digalactosylation of IgG2; decreased agalactosylation of IgG4, bisecting GlcNAc of IgG2) linked to disease state.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11399422" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Decreased galactosylation and sialylation, increased bisecting GlcNAc.", "mechanism": "Reduced galactosylation/sialylation and increased bisecting GlcNAc contribute to chronic inflammation in dyslipidemia.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11399422" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Decreased galactosylation and sialylation, increased fucosylation.", "mechanism": "Decreased galactosylation/sialylation and increased fucosylation linked to 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The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC11402027" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "O-GlcNAc modification at specific sites", "mechanism": "O-GlcNAcylation inhibits \u03b1-synuclein aggregation", "protein": "\u03b1-synuclein", "relationship_type": "protective", "source_pmcid": "PMC11402027" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAc modification regulates protein turnover", "mechanism": "O-GlcNAcylation modulates p53 stability and activity", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11402027" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "O-GlcNAc modification at RelA subunit", "mechanism": "O-GlcNAcylation enhances NF-\u03baB transcriptional activity", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC11402027" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "O-GlcNAc modification at serine residues", "mechanism": "O-GlcNAcylation impairs IRS-1 phosphorylation and signaling", "protein": "Insulin receptor substrate 1 (IRS-1)", "relationship_type": "causal", "source_pmcid": "PMC11402027" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "O-GlcNAc modification at regulatory sites", "mechanism": "O-GlcNAcylation increases FoxO1 transcriptional activity, affecting gluconeogenesis", "protein": "FoxO1", "protein_enriched": { "function": "Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:1589067", "gene_name": "FOXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q12778" }, "relationship_type": "causal", "source_pmcid": "PMC11402027" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAc modification at transactivation domain", "mechanism": "O-GlcNAcylation of Sp1 correlates with tumor progression", "protein": "Sp1", "protein_enriched": { "function": "Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. 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Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11410309" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "O-GlcNAcylation increases Keap1 glycosylation.", "mechanism": "O-GlcNAcylation of Keap1 by OGT leads to degradation of Nrf2, inhibits autophagy, promotes VC.", "protein": "Keap1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "O-GlcNAcylation increases YAP glycosylation.", "mechanism": "O-GlcNAcylation by OGT increases YAP stability, inhibits autophagy, accelerates VC.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "O-GlcNAcylation at T430/T479 enhances AKT activity.", "mechanism": "O-GlcNAcylation of AKT promotes phosphorylation, increases Runx2 activity, promotes VC in diabetes.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "N-glycosylation essential for IGFR function.", "mechanism": "N-glycosylation of IGFR required for IGF-I inhibition of VC; disruption of glycosylation impairs protective effect.", "protein": "IGFR", "relationship_type": "protective", "source_pmcid": "PMC11411399" }, { "confidence": "medium", "disease": "Vascular calcification (VC)", "glycan_involvement": "N-glycosylation regulates TGF-\u03b21 secretion.", "mechanism": "N-glycosylation required for TGF-\u03b21 secretion; inhibition leads to increased cell-associated non-glycosylated TGF-\u03b21.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "medium", "disease": "Vascular calcification (VC)", "glycan_involvement": "N-glycosylation and fucosylation modulate receptor function.", "mechanism": "N-glycosylation and core fucosylation of TGF-\u03b2R required for ligand binding and downstream signaling; inhibition suppresses VC.", "protein": "TGF-\u03b2R", "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "Non-enzymatic glycation of proteins forms AGEs.", "mechanism": "AGEs levels correlate with arterial calcification; AGEs promote VC.", "protein": "AGEs", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "RAGE binds AGEs, propagates signaling.", "mechanism": "RAGE mediates AGE-induced VC; knockdown inhibits VC development.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411399" }, { "confidence": "low", "disease": "Vascular calcification (VC)", "glycan_involvement": "LacdiNAc glycosylation modulates sclerostin function.", "mechanism": "B4GALNT3-mediated LacdiNAc glycosylation of sclerostin may regulate bone/vascular calcification.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "potential therapeutic_target", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Vascular calcification (VC)", "glycan_involvement": "OGT catalyzes O-GlcNAcylation of target proteins.", "mechanism": "OGT overexpression increases glycosylation of Keap1 and YAP, inhibits autophagy, promotes VC; OGT knockdown inhibits VC.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC11411399" }, { "confidence": "high", "disease": "Guillain-Barr\u00e9 syndrome", "glycan_involvement": "Sialylation (Neu5Ac) of LOS mimics host glycans.", "mechanism": "Molecular mimicry of human gangliosides by sialylated LOS induces anti-ganglioside antibodies, leading to autoimmune attack on nerves.", "protein": "Sialylated LOS (Campylobacter jejuni)", "relationship_type": "causal", "source_pmcid": "PMC11413452" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "Neu5Ac capping of LOS prevents recognition by host immune system.", "mechanism": "Sialylation of LOS enables immune evasion by inhibiting complement activation and phagocytosis.", "protein": "Sialylated LOS (Neisseria gonorrhoeae)", "relationship_type": "virulence factor", "source_pmcid": "PMC11413452" }, { "confidence": "high", "disease": "Respiratory tract infection", "glycan_involvement": "Neu5Ac addition to LOS masks bacterial surface.", "mechanism": "Sialylation increases resistance to serum-mediated killing, promoting survival in host.", "protein": "Sialylated LOS (Haemophilus influenzae, esp. 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Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "N-glycosylation defect", "mechanism": "Defective N-glycosylation of T-cell proteins is strongly correlated with T1DM onset.", "protein": "T-cell surface proteins", "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "high", "disease": "Diabetic vasculopathy", "glycan_involvement": "Non-enzymatic glycation (AGE formation)", "mechanism": "AGEs accumulate in tissues, bind AGER, trigger cytokine release and tissue damage.", "protein": "AGE-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Receptor for AGEs (glycated ligands)", "mechanism": "AGER activity in adipocytes promotes hypertrophy, macrophage infiltration, and insulin resistance.", "protein": "AGER (RAGE)", "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation pattern changes", "mechanism": "Specific N-glycan patterns (e.g., increased 2,6-glycosylation) are associated with nephropathy prevalence.", "protein": "Plasma proteins (N-glycosylated)", "relationship_type": "biomarker", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation pattern changes", "mechanism": "Elevated bifurcation on dibasic glycans correlates with CVD in T2DM.", "protein": "Plasma proteins (N-glycosylated)", "relationship_type": "biomarker", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Palmitoylation (lipid modification) of glycoprotein", "mechanism": "Impaired palmitoylation of GLUT4 reduces insulin-stimulated glucose uptake, contributing to insulin resistance.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "O-glycosylation and palmitoylation", "mechanism": "FAS-mediated S-palmitoylation of mucin 2 maintains intestinal mucus barrier; loss increases permeability in diabetes.", "protein": "Mucin 2", "protein_enriched": { "function": "Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces (PubMed:170580", "gene_name": "MUC2", "glycan_count": 55, "glycosylation_sites_count": 45, "glytoucan_ids": [ "G31976RQ", "G22768VO", "G36191CD", "G78059CC", "G00031MO", "G00035MO", "G03172PR", "G03494YC", "G03674DU", "G07932PU", "G10256JP", "G14260UH", "G17810KS", "G19399OS", "G23438NR", "G23870PO", "G25780HH", "G26493RP", "G26915XM", "G27726WH", "G29025YS", "G29931IJ", "G30304IT", "G31685JQ", "G31936TA", "G32405GG", "G32550BI", "G32723SL", "G36447PT", "G38684VZ", "G38887TM", "G39247UK", "G42665KV", "G45939NL", "G49277CJ", "G49582PC", "G50757KG", "G51140AE", "G52902AR", "G54567CI", "G58272ZE", "G58972ZH", "G60554YG", "G61889LW", "G63334FZ", "G63628AV", "G64931FF", "G64973KT", "G69233PF", "G71838YU", "G73423PD", "G74722FL", "G76163CP", "G85228QD", "G94435QH" ], "uniprot_id": "Q02817" }, "relationship_type": "protective", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Protein\u2013glycan receptor interaction", "mechanism": "HMGB1 binds AGER to enhance autophagy and mitigate cell death in adipocytes.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC11442990" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "SUMOylation (not classical glycosylation, but PTM)", "mechanism": "SUMOylation of GAPDH at K332 increases glycolytic activity; loss of SUMOylation worsens neuropathy.", "protein": "GAPDH", "protein_enriched": { "function": "Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde", "gene_name": "GAPDH", "glycan_count": 20, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G05528SJ", "G06356OH", "G11629QQ", "G14547CB", "G20706XG", "G27058EU", "G48414YA", "G56784JY", "G57888GL", "G63136LV", "G65344XH", "G68490OW", "G78787DI", "G90787TS", "G49108TO", "G22310AV", "G43669FQ", "G84452RH", "G70994MS" ], "uniprot_id": "P04406" }, "relationship_type": "protective", "source_pmcid": "PMC11442990" }, { "confidence": "high", "disease": "Acute transplant rejection", "glycan_involvement": "Surface glycosylation may affect SLAMF6 function and exosome uptake.", "mechanism": "Upregulated in acute rejection; regulates T cell activation and differentiation.", "protein": "SLAMF6", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "SLAMF6", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96DU3" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Acute transplant rejection", "glycan_involvement": "Catalyzes N-glycan \u03b1-2,6-sialylation on T cell surface.", "mechanism": "Promotes \u03b1-2,6-sialylation of CD4+ T cells, facilitating T cell activation and rejection.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Acute transplant rejection", "glycan_involvement": "Surface N-glycan \u03b1-2,6-sialylation modulates activation and exosome uptake.", "mechanism": "CD4+ T cell activation and differentiation into Th1/Th17 drives rejection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC11443917" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation status may affect SLAMF6 signaling.", "mechanism": "Promotes Th17 differentiation via ROR\u03b3T recruitment to IL-17A promoter.", "protein": "SLAMF6", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "SLAMF6", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96DU3" }, "relationship_type": "causal", "source_pmcid": "PMC11443917" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Alters N-glycan sialylation on immune cells.", "mechanism": "Aberrant sialylation by ST6GAL1 linked to inflammation and autoimmunity.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Acute cardiac allograft rejection", "glycan_involvement": "Desialylation increases exosome uptake and immunomodulation.", "mechanism": "siRNA knockdown of SLAMF6 in exosomes suppresses T cell activation and prolongs graft survival.", "protein": "SLAMF6", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "SLAMF6", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96DU3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Acute cardiac allograft rejection", "glycan_involvement": "Reduces \u03b1-2,6-sialylation of N-glycans on CD4+ T cells.", "mechanism": "ERC-siSLAMF6 Exos reduce ST6GAL1 expression, decreasing sialylation and T cell activation.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Acute cardiac allograft rejection", "glycan_involvement": "Loss of \u03b1-2,6-sialylation on N-glycans increases exosome uptake and immunosuppression.", "mechanism": "Desialylation of CD4+ T cells inhibits proliferation and differentiation into Th1/Th17, promoting Tregs.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC11443917" }, { "confidence": "medium", "disease": "Acute cardiac allograft rejection", "glycan_involvement": "Exosome glycoprotein composition may affect uptake and function.", "mechanism": "Exosomal marker; ERC-derived exosomes carrying siSLAMF6 are protective.", "protein": "TSG101", "protein_enriched": { "function": "Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicu", "gene_name": "TSG101", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99816" }, "relationship_type": "protective", "source_pmcid": "PMC11443917" }, { "confidence": "medium", "disease": "Acute cardiac allograft rejection", "glycan_involvement": "Exosome glycoprotein composition may affect uptake and function.", "mechanism": "Exosomal marker; ERC-derived exosomes carrying siSLAMF6 are protective.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "protective", "source_pmcid": "PMC11443917" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation likely affects ectodomain stability and release, but specific glycan roles not detailed.", "mechanism": "GPNMB ectodomain is persistently released into serum from LAM tumor cells, and its levels are elevated in LAM patient serum compared to healthy controls. Levels decrease with mTORC1 inhibition.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC11453228" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence cell surface localization and recognition; not explicitly detailed.", "mechanism": "Cell surface expression of GPNMB is unique to LAM tumor cells, making it a potential target for therapy.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453228" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may affect protease cleavage and ectodomain shedding; not explicitly detailed.", "mechanism": "GPNMB regulates TSC2-null tumor cell invasion and xenograft tumor growth; loss of ectodomain shedding halts tumor growth.", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC11453228" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "CD44 is a heavily glycosylated cell surface protein; glycosylation affects ligand binding and cell adhesion.", "mechanism": "CD44 is highly expressed in PAX7/SOX2-positive PitNET cells, marking a population associated with therapy resistance and recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "Splice variants may alter glycosylation patterns, impacting protein function and cell signaling.", "mechanism": "CD44v9 promotes resistance to oxidative stress via stabilization of SLC7A11, contributing to therapy resistance.", "protein": "CD44v9", "protein_enriched": { "function": "", "gene_name": "CD44", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16070-9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation regulates CD44 cleavage and cell surface retention.", "mechanism": "CD44 proteolytic cleavage releases intracellular domain, activating stemness genes (SOX2), driving tumorigenesis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "EpCAM glycosylation modulates cell-cell adhesion and tumor invasiveness.", "mechanism": "EpCAM co-expressed with CD44 in invasive PitNETs, marking stem-like tumor cells.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "CD163 glycosylation affects ligand recognition and macrophage function.", "mechanism": "CD163+ macrophages are increased in invasive PitNETs, indicating an immunosuppressive microenvironment.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "PROM1 glycosylation is essential for stem cell marker function.", "mechanism": "PROM1 marks cancer stem cells in PitNETs, associated with recurrence.", "protein": "PROM1", "protein_enriched": { "function": "May play a role in cell differentiation, proliferation and apoptosis (PubMed:24556617). Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization", "gene_name": "PROM1", "glycan_count": 40, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G07246CJ", "G37818NZ", "G37995HC", "G41071NU", "G42124LM", "G44215PV", "G57776ZS", "G62765YT", "G69521XL", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G82443XX", "G00912UN", "G06356OH", "G20312EM", "G23863VK", "G26403SG", "G27058EU", "G31916IQ", "G36442WJ", "G37412TK", "G48414YA", "G49955PK", "G58954YZ", "G59626AS", "G65184UU", "G70418MS", "G72667IM", "G75983OB", "G81198YO", "G82463GQ", "G83646BJ", "G84452RH", "G91473PK", "G95977AE", "G98611JV", "G63136LV", "G71463BG" ], "uniprot_id": "O43490" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "FUT4 catalyzes fucosylation, impacting cell surface glycan structures.", "mechanism": "FUT4 expression marks stem-like cells in PitNETs, possibly influencing glycan-mediated signaling.", "protein": "FUT4", "protein_enriched": { "function": "Catalyzes alpha(1->3) linkage of fucosyl moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine (GlcNAc) within type 2 lactosamine (LacNAc, Gal-beta(1->4)GlcNAc) glycan attached to N- or O-", "gene_name": "FUT4", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G40926MX", "G41247ZX" ], "uniprot_id": "P22083" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Cushing's disease", "glycan_involvement": "SLC7A11 glycosylation may affect transporter stability and function.", "mechanism": "SLC7A11 stabilization by CD44v9 confers resistance to apoptosis in PitNET cells.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453258" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "Glycosylation status may influence drug binding and efficacy.", "mechanism": "Targeting CD44 variant isoforms may improve efficacy of therapies and prevent recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453258" }, { "confidence": "high", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation modulates CD44-mediated cell adhesion and migration.", "mechanism": "CD44 marks stem-like, therapy-resistant PitNET cells.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453258" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Insulin glycosylation affects stability and receptor binding.", "mechanism": "Elevated fasting insulin indicates impaired insulin signaling.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Altered glycosylation may affect insulin clearance.", "mechanism": "Insulin resistance contributes to hepatic fat accumulation.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation status may modulate insulin activity.", "mechanism": "Elevated insulin is a CM risk factor included in MASLD definition.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "AST is glycosylated, which may affect secretion and stability.", "mechanism": "Elevated AST reflects hepatocellular injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "ALT glycosylation may influence its serum levels.", "mechanism": "Elevated ALT is a marker of liver injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect AST function.", "mechanism": "AST levels are used to assess liver disease severity.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect ALT function.", "mechanism": "ALT levels are used to assess liver disease severity.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate insulin's fibrogenic effects.", "mechanism": "Insulin resistance is associated with progression to fibrosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11453618" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect AST's diagnostic accuracy.", "mechanism": "Elevated AST may indicate advanced liver fibrosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect ALT's diagnostic accuracy.", "mechanism": "Elevated ALT may indicate advanced liver fibrosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453618" }, { "confidence": "high", "disease": "Cholesterol ester storage disease (CESD)", "glycan_involvement": "LIPA is a lysosomal glycoprotein; glycosylation is required for proper folding, stability, and lysosomal targeting.", "mechanism": "Deficiency of LIPA leads to accumulation of cholesterol esters and triglycerides in lysosomes, causing CESD.", "protein": "Lysosomal acid lipase (LIPA/LAL)", "protein_enriched": { "function": "Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed", "gene_name": "LIPA", "glycan_count": 46, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G02815KT", "G03644CB", "G06110VR", "G08290VR", "G11314AS", "G11870QZ", "G27058EU", "G29299MO", "G31852PQ", "G39188ZX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G47518TP", "G47644PP", "G48414YA", "G57776ZS", "G62765YT", "G62894KT", "G66088HZ", "G68490OW", "G70101JE", "G70232NH", "G74724QE", "G79666IR", "G80920RR", "G83460ZZ", "G90382BL", "G92275SC", "G93718GY", "G05724UK", "G28681TP", "G64527OM", "G92050GC", "G43769HG", "G47950XN", "G50282JC", "G59924QI", "G78787DI", "G90575OW", "G92135MA", "G92406TI", "G96091TT", "G20991XV" ], "uniprot_id": "P38571" }, "relationship_type": "causal", "source_pmcid": "PMC11453869" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation of LIPA is essential for lysosomal function.", "mechanism": "LIPA deficiency causes lipid accumulation in hepatocytes, leading to inflammation and fibrosis.", "protein": "Lysosomal acid lipase (LIPA/LAL)", "protein_enriched": { "function": "Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed", "gene_name": "LIPA", "glycan_count": 46, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G02815KT", "G03644CB", "G06110VR", "G08290VR", "G11314AS", "G11870QZ", "G27058EU", "G29299MO", "G31852PQ", "G39188ZX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G47518TP", "G47644PP", "G48414YA", "G57776ZS", "G62765YT", "G62894KT", "G66088HZ", "G68490OW", "G70101JE", "G70232NH", "G74724QE", "G79666IR", "G80920RR", "G83460ZZ", "G90382BL", "G92275SC", "G93718GY", "G05724UK", "G28681TP", "G64527OM", "G92050GC", "G43769HG", "G47950XN", "G50282JC", "G59924QI", "G78787DI", "G90575OW", "G92135MA", "G92406TI", "G96091TT", "G20991XV" ], "uniprot_id": "P38571" }, "relationship_type": "causal", "source_pmcid": "PMC11453869" }, { "confidence": "medium", "disease": "Micronodular cirrhosis", "glycan_involvement": "Glycosylation affects LIPA stability and trafficking.", "mechanism": "Chronic lipid accumulation from LIPA deficiency progresses to cirrhosis.", "protein": "Lysosomal acid lipase (LIPA/LAL)", "protein_enriched": { "function": "Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed", "gene_name": "LIPA", "glycan_count": 46, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G02815KT", "G03644CB", "G06110VR", "G08290VR", "G11314AS", "G11870QZ", "G27058EU", "G29299MO", "G31852PQ", "G39188ZX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G47518TP", "G47644PP", "G48414YA", "G57776ZS", "G62765YT", "G62894KT", "G66088HZ", "G68490OW", "G70101JE", "G70232NH", "G74724QE", "G79666IR", "G80920RR", "G83460ZZ", "G90382BL", "G92275SC", "G93718GY", "G05724UK", "G28681TP", "G64527OM", "G92050GC", "G43769HG", "G47950XN", "G50282JC", "G59924QI", "G78787DI", "G90575OW", "G92135MA", "G92406TI", "G96091TT", "G20991XV" ], "uniprot_id": "P38571" }, "relationship_type": "causal", "source_pmcid": "PMC11453869" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "Glycosylation is required for LIPA lysosomal localization.", "mechanism": "Impaired hydrolysis of cholesterol esters and triglycerides leads to hepatic steatosis.", "protein": "Lysosomal acid lipase (LIPA/LAL)", "protein_enriched": { "function": "Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed", "gene_name": "LIPA", "glycan_count": 46, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G02815KT", "G03644CB", "G06110VR", "G08290VR", "G11314AS", "G11870QZ", "G27058EU", "G29299MO", "G31852PQ", "G39188ZX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G47518TP", "G47644PP", "G48414YA", "G57776ZS", "G62765YT", "G62894KT", "G66088HZ", "G68490OW", "G70101JE", "G70232NH", "G74724QE", "G79666IR", "G80920RR", "G83460ZZ", "G90382BL", "G92275SC", "G93718GY", "G05724UK", "G28681TP", "G64527OM", "G92050GC", "G43769HG", "G47950XN", "G50282JC", "G59924QI", "G78787DI", "G90575OW", "G92135MA", "G92406TI", "G96091TT", "G20991XV" ], "uniprot_id": "P38571" }, "relationship_type": "causal", "source_pmcid": "PMC11453869" }, { "confidence": "low", "disease": "Type 2 diabetes", "glycan_involvement": "Indirect; glycosylation affects LIPA function.", "mechanism": "LIPA deficiency may contribute to metabolic dysregulation and insulin resistance.", "protein": "Lysosomal acid lipase (LIPA/LAL)", "protein_enriched": { "function": "Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed", "gene_name": "LIPA", "glycan_count": 46, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G02815KT", "G03644CB", "G06110VR", "G08290VR", "G11314AS", "G11870QZ", "G27058EU", "G29299MO", "G31852PQ", "G39188ZX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G47518TP", "G47644PP", "G48414YA", "G57776ZS", "G62765YT", "G62894KT", "G66088HZ", "G68490OW", "G70101JE", "G70232NH", "G74724QE", "G79666IR", "G80920RR", "G83460ZZ", "G90382BL", "G92275SC", "G93718GY", "G05724UK", "G28681TP", "G64527OM", "G92050GC", "G43769HG", "G47950XN", "G50282JC", "G59924QI", "G78787DI", "G90575OW", "G92135MA", "G92406TI", "G96091TT", "G20991XV" ], "uniprot_id": "P38571" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453869" }, { "confidence": "high", "disease": "Cholesterol ester storage disease (CESD)", "glycan_involvement": "Therapeutic efficacy depends on correct glycosylation for lysosomal targeting.", "mechanism": "Sebelipase alfa is a recombinant glycoprotein enzyme replacement for LIPA deficiency.", "protein": "Sebelipase alfa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453869" }, { "confidence": "high", "disease": "Hypoinsulinemic hypoglycemia", "glycan_involvement": "Insulin is glycosylated, affecting its stability and clearance.", "mechanism": "Low insulin levels during hypoglycemia indicate impaired pancreatic function or hepatic clearance.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "high", "disease": "Hypoinsulinemic hypoglycemia", "glycan_involvement": "C-peptide glycosylation may affect its half-life and detection.", "mechanism": "Low C-peptide reflects decreased endogenous insulin secretion.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "Prothrombin glycosylation is essential for secretion and function.", "mechanism": "Elevated prothrombin time/INR indicates impaired hepatic synthesis of glycoproteins.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "Glycosylation affects insulin hepatic clearance.", "mechanism": "Liver injury impairs insulin clearance, potentially altering glycoprotein metabolism.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Severe malnutrition", "glycan_involvement": "Glycosylation modulates globulin binding affinity.", "mechanism": "High cortisol levels may reflect altered binding globulin glycosylation in malnutrition.", "protein": "Cortisol-binding globulin", "protein_enriched": { "function": "Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species", "gene_name": "SERPINA6", "glycan_count": 79, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G48414YA", "G00912UN", "G02030ZB", "G06247RL", "G08293MJ", "G10256JP", "G12580WI", "G14994KB", "G15169WU", "G23863VK", "G31916IQ", "G45504EY", "G46687AB", "G47518TP", "G54600FO", "G59937CP", "G83555HU", "G84452RH", "G88725PI", "G94917XT", "G06356OH", "G08918WF", "G10846ZT", "G26330YA", "G31986NC", "G40574BA", "G43223CG", "G45395BF", "G59626AS", "G70232NH", "G70888PK", "G75418YA", "G86880BF", "G29068FM", "G43417UB", "G12341GU", "G27947YN", "G56518TU", "G57776ZS", "G80075MS", "G49108TO", "G05962QB", "G10486CT", "G10819WX", "G11115RO", "G13910DJ", "G22310AV", "G28681TP", "G29545VG", "G31852PQ", "G34617SM", "G37818NZ", "G39595FH", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43669FQ", "G44753VC", "G47737VJ", "G52527GH", "G53075ES", "G57776ZU", "G59324HL", "G59536GA", "G62461SM", "G62765YT", "G63136LV", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G81637OR", "G82830MN", "G87123QX", "G94665LC", "G95865ZB", "G99668VU", "G99679NM" ], "uniprot_id": "P08185" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Multiorgan failure", "glycan_involvement": "Glycosylation required for prothrombin activity.", "mechanism": "Deranged prothrombin time is a marker of systemic dysfunction.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Severe malnutrition", "glycan_involvement": "Glycosylation may be altered in malnutrition, affecting insulin stability.", "mechanism": "Malnutrition leads to decreased insulin secretion.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "Glycosylation affects C-peptide clearance.", "mechanism": "Low C-peptide may reflect impaired hepatic metabolism.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion.", "mechanism": "Prolonged prothrombin time is a marker of hepatic synthetic failure.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "medium", "disease": "Multiorgan failure", "glycan_involvement": "Glycosylation status may be altered in systemic disease.", "mechanism": "Low insulin in multiorgan failure reflects pancreatic and hepatic dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454189" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSI glycosylation affects antibody stability and receptor binding.", "mechanism": "TSI binds and activates TSHR, causing hyperthyroidism.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC11454244" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TRAb glycosylation modulates immune recognition and effector function.", "mechanism": "TRAb stimulates TSHR, leading to increased thyroid hormone production.", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC11454244" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSHR N-glycosylation is critical for receptor folding and antibody binding.", "mechanism": "TSHR is activated by autoantibodies, driving disease pathology.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454244" }, { "confidence": "high", "disease": "Paget's disease of bone", "glycan_involvement": "ALP is an N-glycosylated glycoprotein; glycosylation affects its stability and secretion, enabling its use as a serum biomarker.", "mechanism": "Elevated ALP levels reflect increased bone turnover and osteoblastic activity characteristic of Paget's disease.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454360" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Hypoglycosylation reduces IGF-1 stability and secretion.", "mechanism": "Low serum IGF-1 is common in PMM2-CDG due to impaired glycosylation.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Glycosylation required for IGFBP3 stability and IGF-1 binding.", "mechanism": "Low IGFBP3 levels reflect impaired glycosylation and destabilization of IGF-1 ternary complex.", "protein": "IGFBP3", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "ALS glycosylation is essential for complex formation with IGF-1 and IGFBP3.", "mechanism": "Low ALS levels due to hypoglycosylation destabilize IGF-1 ternary complex.", "protein": "ALS", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "Short stature", "glycan_involvement": "Glycosylation defects decrease IGF-1 half-life and secretion.", "mechanism": "Reduced IGF-1 bioavailability leads to impaired growth.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "GH insensitivity", "glycan_involvement": "Hypoglycosylation impairs IGF-1 system responsiveness to GH.", "mechanism": "Normal GH production but low IGF-1 due to glycosylation defects causes GH insensitivity.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC11454461" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Glycosylation required for maturation and secretion.", "mechanism": "Impaired glycosylation reduces proIGF-1Ea processing and secretion.", "protein": "proIGF-1Ea", "relationship_type": "causal", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Glycosylation of IGFBP3 and ALS is critical for complex stability.", "mechanism": "Destabilization of ternary complex reduces IGF-1 half-life.", "protein": "IGF-1/IGFBP3/ALS ternary complex", "relationship_type": "causal", "source_pmcid": "PMC11454461" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Indirect effect via impaired glycosylation.", "mechanism": "GH insensitivity and low IGF-1 may contribute to obesity in PMM2-CDG.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "Indirect effect via glycosylation defects.", "mechanism": "Low IGF-1 may be associated with metabolic disturbances.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Indirect effect via glycosylation defects.", "mechanism": "Low IGF-1 may contribute to liver dysfunction in PMM2-CDG.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC11454461" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "CD44 is a heavily glycosylated transmembrane protein; glycosylation affects ligand binding and cell adhesion.", "mechanism": "CD44 expression on PAX7/SOX2-positive PitNET cells defines a population contributing to therapy resistance and recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454625" }, { "confidence": "high", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation of CD44v9 may modulate its interaction with SLC7A11 and stemness signaling.", "mechanism": "CD44v9 promotes resistance to reactive oxygen species (ROS) via stabilization of SLC7A11, supporting tumor cell survival.", "protein": "CD44v9", "protein_enriched": { "function": "", "gene_name": "CD44", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16070-9" }, "relationship_type": "causal", "source_pmcid": "PMC11454625" }, { "confidence": "high", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation regulates CD44's role in cell-cell and cell-matrix interactions.", "mechanism": "CD44 marks cancer stem cell populations associated with invasiveness and recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11454625" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "EpCAM glycosylation influences cell adhesion and tumorigenicity.", "mechanism": "EpCAM co-expressed with CD44 in invasive PitNET subtypes, marking stem-like tumor cells.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454625" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "CD163 glycosylation affects receptor function and immune modulation.", "mechanism": "CD163+ macrophages are increased in invasive PitNETs, indicating an immunosuppressive microenvironment.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454625" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "PROM1 glycosylation is critical for stem cell marker function.", "mechanism": "PROM1 marks stem cell populations in PitNETs, associated with proliferation and therapy resistance.", "protein": "PROM1 (CD133)", "relationship_type": "biomarker", "source_pmcid": "PMC11454625" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "FUT4 mediates fucosylation, impacting glycoprotein function and cell signaling.", "mechanism": "FUT4 expression in stem cell populations may contribute to tumor progression via fucosylation of surface glycoproteins.", "protein": "FUT4", "protein_enriched": { "function": "Catalyzes alpha(1->3) linkage of fucosyl moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine (GlcNAc) within type 2 lactosamine (LacNAc, Gal-beta(1->4)GlcNAc) glycan attached to N- or O-", "gene_name": "FUT4", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G40926MX", "G41247ZX" ], "uniprot_id": "P22083" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454625" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "Glycosylation state may affect antibody or drug binding to CD44.", "mechanism": "Targeting CD44 variant isoforms may improve efficacy of medical and radiosurgical therapies to prevent recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454625" }, { "confidence": "medium", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation may regulate susceptibility to proteolytic cleavage.", "mechanism": "Proteolytic cleavage of CD44 releases its intracellular domain, activating stemness genes (SOX2) and promoting tumorigenesis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11454625" }, { "confidence": "high", "disease": "Pituitary neuroendocrine tumor (PitNET)", "glycan_involvement": "Glycosylation of CD44 may modulate its interaction with SLC7A11 and apoptosis resistance.", "mechanism": "Co-expression renders tumor cells resistant to radiation-induced apoptosis.", "protein": "CD44/SLCA7A11", "relationship_type": "causal", "source_pmcid": "PMC11454625" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect ectodomain shedding and detection.", "mechanism": "GPNMB ectodomain is released into serum at higher levels in LAM patients; levels decrease with mTORC1 inhibition.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC11454939" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence cell surface localization and antibody targeting.", "mechanism": "Cell surface GPNMB is uniquely expressed on LAM tumor cells, making it a potential target for therapy.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454939" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may modulate GPNMB function and protease accessibility.", "mechanism": "GPNMB regulates TSC2-null tumor cell invasion and xenograft tumor growth; loss of ectodomain shedding halts tumor growth.", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC11454939" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSHR is a glycoprotein; glycosylation is essential for proper folding and cell surface expression, influencing autoantibody binding.", "mechanism": "Autoantibodies stimulate TSHR, leading to hyperthyroidism.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC11455131" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSI is an immunoglobulin glycoprotein; glycosylation affects stability and receptor interaction.", "mechanism": "TSI binds and activates TSHR, causing increased thyroid hormone production.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC11455131" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TRAb glycosylation modulates antibody function and immune recognition.", "mechanism": "TRAb levels correlate with disease activity; they stimulate or block TSHR.", "protein": "Thyrotropin Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC11455131" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect ectodomain shedding and detection.", "mechanism": "GPNMB ectodomain is released into serum from LAM tumor cells; serum levels are higher in LAM patients and decrease with mTORC1 inhibition.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455371" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence GPNMB cell surface localization and protease cleavage.", "mechanism": "Cell surface GPNMB is selectively expressed on LAM tumor cells; blocking ectodomain shedding halts tumor growth.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11455371" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may modulate GPNMB function in cell signaling and tumor progression.", "mechanism": "GPNMB regulates TSC2-null tumor cell invasion and xenograft tumor growth.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "causal", "source_pmcid": "PMC11455371" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect ectodomain shedding and detection.", "mechanism": "GPNMB ectodomain is released into serum from TSC2-null tumor cells; serum levels are elevated in LAM patients and decrease with mTORC1 inhibition.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455463" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence GPNMB cell surface stability and protease accessibility.", "mechanism": "Cell surface GPNMB is selectively expressed on LAM tumor cells; blocking ectodomain shedding halts TSC2-null tumor growth.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11455463" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may modulate GPNMB function in cell signaling and invasion.", "mechanism": "GPNMB regulates TSC2-null tumor cell invasion and xenograft tumor growth.", "protein": "Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)", "protein_enriched": { "function": "Could be a melanogenic enzyme", "gene_name": "GPNMB", "glycan_count": 211, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08609CW", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G12313PD", "G14547CB", "G14669DU", "G17208MA", "G18647XP", "G20210JR", "G20528HD", "G23294PN", "G23719VF", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G33416PL", "G33609NS", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37412TK", "G37509XX", "G37692EO", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G41840AI", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G47950XN", "G49642SA", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G65184UU", "G68735SN", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G84349RE", "G85269DF", "G86880BF", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92275SC", "G92406TI", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G01485JJ", "G01521EA", "G05962QB", "G08290VR", "G09831WQ", "G11115RO", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G25079LO", "G25451PN", "G27915IV", "G29545VG", "G32788FZ", "G35541EV", "G37818NZ", "G41071NU", "G42124LM", "G45526EA", "G47012YE", "G52890YB", "G53075ES", "G57776ZS", "G58087IP", "G62894KT", "G64409MC", "G64527OM", "G66537LK", "G67164EE", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G74381CZ", "G74724QE", "G75983OB", "G76295SF", "G76868JS", "G80075MS", "G80479JV", "G81637OR", "G84452RH", "G85282JO", "G87123QX", "G90382BL", "G93718GY", "G95046LV", "G99679NM", "G01160VV", "G02528FI", "G04657PL", "G06356OH", "G07755XJ", "G07810QS", "G09700PF", "G12261QD", "G12341GU", "G12745LE", "G13131HA", "G16125XL", "G20706XG", "G23505EP", "G29580WD", "G29880MM", "G30221QT", "G30740WO", "G31309XD", "G31916IQ", "G34029GR", "G34617SM", "G34989PA", "G40206WX", "G43669FQ", "G46503DX", "G47518TP", "G48414YA", "G49018RC", "G49755GI", "G49906RN", "G50856PC", "G52848YE", "G55132BD", "G56518TU", "G59536GA", "G60967DT", "G63040RU", "G63136LV", "G63980BQ", "G70223PD", "G70888PK", "G71463BG", "G72790NZ", "G73430PD", "G75568BH", "G77547TA", "G77669RF", "G82443XX", "G84225JN", "G84862VB", "G85554PZ", "G86182NS", "G87389XI", "G87661QW", "G92135MA", "G92551JA", "G94310CV", "G94665LC", "G98129XB", "G99668VU", "G43417UB", "G15664MX", "G29184RN", "G47702MW", "G83633GK", "G49108TO" ], "uniprot_id": "Q14956" }, "relationship_type": "causal", "source_pmcid": "PMC11455463" }, { "confidence": "high", "disease": "LGMDR9", "glycan_involvement": "Defective O-mannosyl glycan modification of \u03b1-DG", "mechanism": "Pathogenic FKRP variants impair glycosylation of \u03b1-dystroglycan, disrupting muscle cell membrane integrity.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "MDC1C", "glycan_involvement": "Impaired O-mannosyl glycan synthesis on \u03b1-DG", "mechanism": "FKRP mutations cause severe reduction in \u03b1-DG glycosylation, leading to congenital muscular dystrophy.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "WWS", "glycan_involvement": "Loss of functional O-mannosyl glycan on \u03b1-DG", "mechanism": "FKRP mutations result in defective glycosylation of \u03b1-DG, causing severe brain and muscle pathology.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "MEB", "glycan_involvement": "Defective O-mannosyl glycan modification", "mechanism": "FKRP mutations disrupt \u03b1-DG glycosylation, affecting muscle, eye, and brain development.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "Duchenne/Becker-like phenotype", "glycan_involvement": "Reduced glycosylation of \u03b1-DG", "mechanism": "FKRP mutations can mimic DMD/BMD phenotype due to secondary dystrophin reduction and \u03b1-DG hypoglycosylation.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Defective O-mannosyl glycan on \u03b1-DG", "mechanism": "FKRP mutations weaken sarcolemma via impaired \u03b1-DG glycosylation, increasing susceptibility to mechanical stress in cardiomyocytes.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "medium", "disease": "Brain abnormalities (neuronal migration defects)", "glycan_involvement": "Defective O-mannosyl glycan on \u03b1-DG", "mechanism": "FKRP mutations impair \u03b1-DG glycosylation, essential for normal brain development and neuronal migration.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "LGMDR9", "glycan_involvement": "O-mannosyl glycan status", "mechanism": "Reduced glycosylation of \u03b1-DG is a diagnostic marker for FKRP-related muscular dystrophies.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11476872" }, { "confidence": "medium", "disease": "LGMDR9", "glycan_involvement": "Targeting O-mannosyl glycan pathway", "mechanism": "Restoring FKRP function or \u03b1-DG glycosylation may ameliorate disease symptoms.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11476872" }, { "confidence": "medium", "disease": "LGMDR9", "glycan_involvement": "Disrupted O-mannosyl glycan modification", "mechanism": "p.R143S variant alters FKRP structure and dynamics, reducing flexibility and impairing glycosylation activity.", "protein": "FKRP (p.R143S variant)", "relationship_type": "causal", "source_pmcid": "PMC11476872" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type Iw (CDG-Iw)", "glycan_involvement": "Loss of N-glycosylation at Asn544 impairs OST function and global protein glycosylation.", "mechanism": "Heterozygous pathogenic variants in STT3A disrupt N-glycosylation of proteins, causing CDG-Iw.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11491968" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type Iw (CDG-Iw)", "glycan_involvement": "Defective N-glycosylation leads to increased mono-oligosaccharide transferrin.", "mechanism": "Hypoglycosylated transferrin isoforms are detected in plasma of CDG-Iw patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11491968" }, { "confidence": "medium", "disease": "Congenital disorder of glycosylation type Iw (CDG-Iw)", "glycan_involvement": "Changes in O-glycosylation patterns of ApoCIII.", "mechanism": "Altered glycoforms of ApoCIII are observed in CDG-Iw, reflecting glycosylation defects.", "protein": "Apolipoprotein CIII", "protein_enriched": { "function": "Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma (PubMed:18201179, PubMed:22510806). Plays a multifaceted role in triglyceride homeosta", "gene_name": "APOC3", "glycan_count": 10, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G01614ZM", "G17015OC", "G29931IJ", "G43417UB", "G65562ZE", "G68008QO", "G74722FL", "G81006GJ", "G49108TO" ], "uniprot_id": "P02656" }, "relationship_type": "biomarker", "source_pmcid": "PMC11491968" }, { "confidence": "medium", "disease": "Neurodevelopmental disorders (autism, ADHD, developmental delay)", "glycan_involvement": "Global N-glycosylation defects in neural tissue.", "mechanism": "Impaired N-glycosylation of neural proteins due to STT3A mutation affects brain development.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11491968" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Impaired N-glycosylation in neurons.", "mechanism": "Defective glycosylation of neuronal proteins may contribute to seizure susceptibility.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11491968" }, { "confidence": "medium", "disease": "Failure to thrive/short stature", "glycan_involvement": "Defective N-glycosylation of growth-related proteins.", "mechanism": "Disrupted glycosylation affects growth factor and hormone receptor function.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11491968" }, { "confidence": "medium", "disease": "Skeletal anomalies", "glycan_involvement": "Impaired N-glycosylation of structural proteins.", "mechanism": "Abnormal glycosylation of extracellular matrix proteins impacts skeletal development.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11491968" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "Catalyzes O-glycosylation (sialylation) to produce Sialyl-Tn antigen on glycoproteins.", "mechanism": "Upregulation of SIAT7A promotes synthesis of Sialyl-Tn antigen, leading to cardiomyocyte hypertrophy via activation of hypertrophic signaling pathways.", "protein": "SIAT7A (ST6GalNAc I)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3R4" }, "relationship_type": "causal", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "O-glycosylation (sialylation) of GalNAc-O-Ser/Thr residues.", "mechanism": "Increased expression of Sialyl-Tn antigen correlates with hypertrophic myocardium.", "protein": "Sialyl-Tn antigen", "relationship_type": "biomarker", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "KLF4 transcriptional activity is enhanced by SIAT7A-mediated sialylation.", "mechanism": "KLF4 upregulation induces SIAT7A expression, promoting hypertrophy; forms a positive feedback loop with SIAT7A.", "protein": "KLF4", "protein_enriched": { "function": "Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates th", "gene_name": "KLF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43474" }, "relationship_type": "causal", "source_pmcid": "PMC11492152" }, { "confidence": "medium", "disease": "Essential hypertension", "glycan_involvement": "Increased sialylation of cardiac glycoproteins.", "mechanism": "Elevated SIAT7A detected in hypertrophic myocardium of hypertensive patients.", "protein": "SIAT7A (ST6GalNAc I)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3R4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11492152" }, { "confidence": "medium", "disease": "Essential hypertension", "glycan_involvement": "Indirect, via SIAT7A-mediated sialylation.", "mechanism": "KLF4 levels are increased in hypertrophic myocardium of hypertensive patients.", "protein": "KLF4", "protein_enriched": { "function": "Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates th", "gene_name": "KLF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43474" }, "relationship_type": "biomarker", "source_pmcid": "PMC11492152" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "O-glycosylation (sialylation) of cardiac glycoproteins.", "mechanism": "Aberrant sialylation by SIAT7A is associated with heart failure.", "protein": "SIAT7A (ST6GalNAc I)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3R4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11492152" }, { "confidence": "low", "disease": "Arrhythmia", "glycan_involvement": "O-glycosylation (sialylation) of cardiac glycoproteins.", "mechanism": "Abnormal glycosylation linked to arrhythmia pathogenesis.", "protein": "SIAT7A (ST6GalNAc I)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3R4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "Reduces Sialyl-Tn antigen synthesis.", "mechanism": "Knockdown of SIAT7A inhibits hypertrophy, suggesting therapeutic potential.", "protein": "SIAT7A (ST6GalNAc I)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3R4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "Disrupts positive feedback with SIAT7A-mediated sialylation.", "mechanism": "Knockdown of KLF4 reduces SIAT7A and Sialyl-Tn, attenuating hypertrophy.", "protein": "KLF4", "protein_enriched": { "function": "Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates th", "gene_name": "KLF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43474" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "Myocardial hypertrophy", "glycan_involvement": "O-glycosylation (sialylation) of cardiac glycoproteins.", "mechanism": "Sialyl-Tn antigen expression promotes hypertrophic signaling in cardiomyocytes.", "protein": "Sialyl-Tn antigen", "relationship_type": "causal", "source_pmcid": "PMC11492152" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Loss of O-linked matriglycan modification", "mechanism": "Hypoglycosylation (loss of matriglycan) on \u03b1-DG impairs binding to extracellular ligands, compromising muscle membrane integrity.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11503271" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Defective O-mannosylation (matriglycan polymerization)", "mechanism": "Mutations in LARGE1 reduce matriglycan synthesis on \u03b1-DG, leading to disease.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC11503271" }, { "confidence": "high", "disease": "limb-girdle muscular dystrophy", "glycan_involvement": "Defective O-linked matriglycan modification", "mechanism": "Aberrant glycosylation of \u03b1-DG disrupts its receptor function for extracellular matrix proteins.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11503271" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Enhanced O-linked matriglycan on mucin-like domain", "mechanism": "Engineered GBi antibody restores linkage between laminin-211 and \u03b2-DG, compensating for defective \u03b1-DG glycosylation.", "protein": "GBi antibody", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11503271" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Requires matriglycan on \u03b1-DG for binding", "mechanism": "Binding of laminin-211 to properly glycosylated \u03b1-DG maintains muscle membrane stability.", "protein": "Laminin-211", "protein_enriched": { "function": "Plays a role in embryonic morphogenesis; it is involved in the regulation of endochondral skeleton formation, and the development of retinal pigment epithelium (RPE), photoreceptors and periocular tis", "gene_name": "IHH", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q14623" }, "relationship_type": "protective", "source_pmcid": "PMC11503271" }, { "confidence": "medium", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Indirectly facilitates proper glycosylation", "mechanism": "PACE removes \u03b1-DG prodomain post-matriglycan modification, enabling functional GBi antibody production.", "protein": "PACE (Furin)", "protein_enriched": { "function": "Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, PubMed:24666235, Pu", "gene_name": "FURIN", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P09958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11503271" }, { "confidence": "medium", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Requires matriglycan for binding", "mechanism": "Agrin binds to matriglycan-modified \u03b1-DG, contributing to extracellular matrix interactions.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "protective", "source_pmcid": "PMC11503271" }, { "confidence": "medium", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Requires matriglycan for binding", "mechanism": "Neurexin interacts with matriglycan-modified \u03b1-DG, supporting cell adhesion.", "protein": "Neurexin", "relationship_type": "protective", "source_pmcid": "PMC11503271" }, { "confidence": "medium", "disease": "\u03b1-dystroglycanopathies", "glycan_involvement": "Requires matriglycan for binding", "mechanism": "Perlecan binds matriglycan on \u03b1-DG, aiding basement membrane integrity.", "protein": "Perlecan", "protein_enriched": { "function": "Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is b", "gene_name": "HSPG2", "glycan_count": 183, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G43417UB", "G57321FI", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G08918WF", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G14972EH", "G20706XG", "G23719VF", "G27058EU", "G27126ED", "G34989PA", "G35029YA", "G36379GD", "G37412TK", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44437FL", "G45395BF", "G45504EY", "G46691LC", "G47702MW", "G49955PK", "G57776ZU", "G59626AS", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G77669RF", "G80920RR", "G83633GK", "G86182NS", "G87661QW", "G90382BL", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G95177YH", "G95865ZB", "G29068FM", "G58001LT", "G73004SD", "G40740AD", "G57317CE", "G53434XO", "G00273SJ", "G01650EU", "G02528FI", "G03382KH", "G04854VP", "G09197ZW", "G10773YW", "G10846ZT", "G11870QZ", "G12341GU", "G14994KB", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G23505EP", "G23863VK", "G23984SE", "G25418HZ", "G25451PN", "G28541PG", "G28681TP", "G29184RN", "G29299MO", "G31028YV", "G31852PQ", "G35253PZ", "G37399XV", "G37509XX", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41840AI", "G44215PV", "G46503DX", "G46687AB", "G46902YN", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51640FO", "G59924QI", "G63041LO", "G65092SV", "G68490OW", "G73430PD", "G73968GN", "G75983OB", "G77547TA", "G79666IR", "G80223IX", "G82463GQ", "G82830MN", "G83646BJ", "G84349RE", "G84452RH", "G84820NF", "G85554PZ", "G87389XI", "G88891KO", "G92062TF", "G96091TT", "G98611JV", "G99679NM", "G01485JJ", "G22572EH", "G27947YN", "G37995HC", "G43669FQ", "G43734MM", "G57776ZS", "G60033FS", "G60834IK", "G75418YA", "G80075MS", "G84862VB", "G86880BF", "G87123QX", "G89045VA", "G91636VS", "G94470IW", "G49108TO", "G22310AV", "G83229XP", "G81006GJ", "G29931IJ", "G02628JF", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G20425TQ", "G23432EQ", "G25079LO", "G26330YA", "G31986NC", "G33609NS", "G37818NZ", "G39188ZX", "G43769HG", "G49906RN", "G52527GH", "G55383ZG", "G64527OM", "G69521XL", "G70223PD", "G72291OX", "G72398FA", "G78790NZ", "G83460ZZ", "G84225JN", "G86795LJ", "G89098OM", "G99668VU" ], "uniprot_id": "P98160" }, "relationship_type": "protective", "source_pmcid": "PMC11503271" }, { "confidence": "high", "disease": "congenital muscular dystrophy", "glycan_involvement": "Loss of O-linked matriglycan modification", "mechanism": "Mutations in glycosylation pathway genes cause hypoglycosylation of \u03b1-DG, leading to muscular dystrophy.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11503271" }, { "confidence": "medium", "disease": "Methicillin-resistant Staphylococcus aureus infection (MRSA)", "glycan_involvement": "Glycosylation may affect PBP2a stability and function.", "mechanism": "PBP2a confers resistance to beta-lactam antibiotics, leading to MRSA.", "protein": "Staphylococcus aureus PBP2a", "relationship_type": "causal", "source_pmcid": "PMC11504134" }, { "confidence": "medium", "disease": "Fluoroquinolone-resistant Escherichia coli infection", "glycan_involvement": "Glycosylation can modulate membrane protein function and antibiotic permeability.", "mechanism": "Altered outer membrane proteins contribute to fluoroquinolone resistance.", "protein": "Escherichia coli outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC11504134" }, { "confidence": "medium", "disease": "Carbapenem-resistant Enterobacterales infection", "glycan_involvement": "Altered glycosylation affects drug binding and immune recognition.", "mechanism": "Surface glycoproteins mediate antibiotic resistance and immune evasion.", "protein": "Enterobacterales glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Extended-spectrum cephalosporin-resistant Enterobacterales infection", "glycan_involvement": "Glycan structures modulate antibiotic susceptibility.", "mechanism": "Glycoprotein modifications contribute to resistance phenotype.", "protein": "Enterobacterales glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Carbapenem-non-susceptible Pseudomonas aeruginosa infection", "glycan_involvement": "Glycosylation alters membrane properties and resistance.", "mechanism": "Outer membrane glycoproteins reduce drug permeability.", "protein": "Pseudomonas aeruginosa glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Fluoroquinolone-resistant Pseudomonas aeruginosa infection", "glycan_involvement": "Glycan modifications impact efflux pump function.", "mechanism": "Glycoprotein-mediated efflux and drug exclusion.", "protein": "Pseudomonas aeruginosa glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Fluoroquinolone-resistant Enterobacterales infection", "glycan_involvement": "Glycosylation modulates membrane permeability.", "mechanism": "Glycoprotein changes affect drug uptake and resistance.", "protein": "Enterobacterales glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Carbapenem-resistant Enterobacterales infection", "glycan_involvement": "Capsule glycosylation impedes antibiotic access.", "mechanism": "Capsular glycoproteins contribute to resistance and virulence.", "protein": "Klebsiella spp. glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Carbapenem-resistant Enterobacterales infection", "glycan_involvement": "Glycan structures influence drug susceptibility.", "mechanism": "Surface glycoproteins mediate resistance mechanisms.", "protein": "Escherichia coli glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "medium", "disease": "Carbapenem-resistant Enterobacterales infection", "glycan_involvement": "Glycosylation affects antibiotic binding.", "mechanism": "Glycoprotein modifications linked to resistance phenotype.", "protein": "Enterobacter spp. glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11504446" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dp71 is part of the dystrophin-associated glycoprotein complex (DGC), which is heavily glycosylated.", "mechanism": "Dp71 deficiency disrupts glutamatergic and GABAergic synaptic transmission, impairing brain plasticity and contributing to cognitive and motor deficits.", "protein": "Dystrophin (Dp71)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-8" }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "Pathogenic mechanism is defective O-glycosylation of \u03b1-DG.", "mechanism": "Defective glycosylation of \u03b1-DG impairs clustering of GABA A receptors in CNS synapses, leading to enhanced LTP and increased epilepsy risk.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "high", "disease": "Laminin \u03b12-related Congenital Muscular Dystrophy", "glycan_involvement": "Laminin \u03b12 is a glycoprotein interacting with glycosylated \u03b1-DG for synaptic anchoring.", "mechanism": "Laminin \u03b12 deficiency impairs LTD in cerebellar Purkinje cells, causing motor learning deficits.", "protein": "Laminin \u03b12", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMB3", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G62765YT", "G80920RR", "G49108TO", "G57321FI" ], "uniprot_id": "Q13751" }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "medium", "disease": "Centronuclear Myopathy (CNM)", "glycan_involvement": "Dyn2 regulates trafficking of glycosylated receptors.", "mechanism": "Dyn2 mutations impair postsynaptic AMPA receptor trafficking, reducing synaptic plasticity and causing cognitive deficits.", "protein": "Dynamin-2 (Dyn2)", "protein_enriched": { "function": "Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the a", "gene_name": "DNM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "P50570" }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "SMN interacts with glycoprotein complexes at synapses.", "mechanism": "SMN deficiency leads to defective synaptic maintenance at CNS and NMJ, impairing plasticity and motor function.", "protein": "SMN protein", "protein_enriched": { "function": "The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (", "gene_name": "SMN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16637" }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "high", "disease": "Myotonic Dystrophy Type 1 (DM1)", "glycan_involvement": "Mis-splicing affects glycoprotein expression and function.", "mechanism": "DMPK mutation causes toxic RNA foci, mis-splicing of glycoprotein genes, and impaired synaptic plasticity.", "protein": "DMPK", "protein_enriched": { "function": "Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the", "gene_name": "DMPK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q09013" }, "relationship_type": "causal", "source_pmcid": "PMC11506792" }, { "confidence": "medium", "disease": "Myotonic Dystrophy Type 1 (DM1)", "glycan_involvement": "GLT1 is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "Downregulation of astrocytic GLT1 impairs glutamate clearance, contributing to excitotoxicity and synaptic dysfunction.", "protein": "GLT1 (EAAT2)", "protein_enriched": { "function": "Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:20477940, PubMed:26690923, PubMed:28032905, PubMed:28424515,", "gene_name": "SLC1A3", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11101UV", "G20706XG", "G53434XO", "G64409MC" ], "uniprot_id": "P43003" 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"MUC5B", "protein_enriched": { "function": "Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus", "gene_name": "MUC5B", "glycan_count": 47, "glycosylation_sites_count": 38, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G62765YT", "G80920RR", "G84452RH", "G48414YA", "G66760KM", "G57321FI", "G64527OM", "G39188ZX", "G31852PQ", "G70822IO", "G75983OB", "G05724UK", "G06110VR", "G10773YW", "G29880MM", "G46687AB", "G82119TF", "G02030ZB", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G40142JY", "G42665KV", "G49582PC", "G58272ZE", "G63110FE", "G63628AV", "G63760GT", "G64973KT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G78315FS", "G79243QP", "G81006GJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q9HC84" }, "relationship_type": "causal", "source_pmcid": "PMC11523070" }, { "confidence": "high", "disease": "Carotid atherosclerosis (CAS)", "glycan_involvement": "Lower N-fucosylation on IgG Fc domain", "mechanism": "Reduced IgG fucosylation (afucosylation) enhances ADCC and inflammatory response, promoting CAS development.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11529013" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycan modifications on Fc domain", "mechanism": "Altered IgG N-glycosylation profiles (especially afucosylation) increase inflammatory potential, contributing to atherosclerosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Altered N-glycan traits", "mechanism": "IgG N-glycosylation profiles are associated with T2DM pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycan modifications", "mechanism": "IgG N-glycosylation changes (including afucosylation) modulate immune response in COVID-19.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "N-glycan 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"protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "N-glycan traits", "mechanism": "IgG N-glycosylation changes are linked to PD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "N-glycan modifications", "mechanism": "IgG N-glycosylation profiles are associated with ischemic stroke.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "medium", "disease": "Biological aging", "glycan_involvement": "N-glycan modifications", "mechanism": "IgG N-glycosylation profiles change with aging and can track cardiovascular risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11529013" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins.", "mechanism": "Deficiency in PMM2 impairs N-glycan precursor synthesis, leading to multisystem disease.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "high", "disease": "ALG6-CDG", "glycan_involvement": "Impaired N-glycosylation.", "mechanism": "ALG6 mutations disrupt N-glycan assembly, causing CDG symptoms.", "protein": "ALG6", "protein_enriched": { "function": "Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)", "gene_name": "ALG6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9Y672" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "high", "disease": "PIGA-CDG", "glycan_involvement": "Defective GPI-anchor glycosylation.", "mechanism": "PIGA defects impair GPI-anchor biosynthesis, affecting cell surface protein anchoring.", "protein": "PIGA", "protein_enriched": { "function": "Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidyli", "gene_name": "PIGA", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37287" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "B3GAT3-CDG", "glycan_involvement": "Abnormal O-xylose glycosaminoglycan modification.", "mechanism": "B3GAT3 mutations cause O-xylose glycosaminoglycan defects, leading to CDG.", "protein": "B3GAT3", "protein_enriched": { "function": "Glycosaminoglycans biosynthesis (PubMed:25893793). Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridi", "gene_name": "B3GAT3", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "O94766" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "B4GALT7-CDG", "glycan_involvement": "Defective O-xylose glycosaminoglycan modification.", "mechanism": "B4GALT7 mutations disrupt O-xylose glycosaminoglycan biosynthesis.", "protein": "B4GALT7", "protein_enriched": { "function": "Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormon", "gene_name": "CACNA1F", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O60840" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "CCDC115-CDG", "glycan_involvement": "Multiple glycosylation pathway defects.", "mechanism": "CCDC115 defects impair Golgi function, affecting glycosylation.", "protein": "CCDC115", "protein_enriched": { "function": "Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide do", "gene_name": "MAGT1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9H0U3" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "COG-CDG", "glycan_involvement": "Defective N- and O-glycosylation.", "mechanism": "COG complex mutations disrupt Golgi trafficking, impairing glycosylation.", "protein": "COG complex", "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "ATP6VOA2-CDG", "glycan_involvement": "Defective glycosylation due to Golgi dysfunction.", "mechanism": "ATP6VOA2 mutations impair Golgi acidification, affecting glycosylation.", "protein": "ATP6VOA2", "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "GALNT2-CDG", "glycan_involvement": "Defective O-glycosylation of mucin core1.", "mechanism": "GALNT2 mutations impair mucin-type O-glycosylation.", "protein": "GALNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spect", "gene_name": "GALNT2", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q10471" }, "relationship_type": "causal", "source_pmcid": "PMC11529564" }, { "confidence": "medium", "disease": "COG-CDG", "glycan_involvement": "Altered O-glycosylation pattern detectable in plasma.", "mechanism": "Defects in mucin core1 O-glycosylation of ApoC-III serve as a biomarker for Golgi impairment.", "protein": "Apolipoprotein C-III", "relationship_type": "biomarker", "source_pmcid": "PMC11529564" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Beta-2 glycoprotein 1 is a glycoprotein; glycosylation affects its antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein 1 are diagnostic for APS and promote thrombosis.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535572" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycoproteins such as beta-2 glycoprotein 1; glycosylation may modulate epitope exposure.", "mechanism": "Lupus anticoagulant is an autoantibody that targets phospholipid-binding glycoproteins, increasing thrombosis risk.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC11535572" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Binding depends on glycosylated beta-2 glycoprotein 1 structure.", "mechanism": "Anticardiolipin antibodies bind to cardiolipin-beta-2 glycoprotein 1 complexes, promoting clot formation.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11535572" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Sm antigens are ribonucleoproteins; glycosylation may affect antigen processing but not primary mechanism.", "mechanism": "Anti-Sm antibodies are highly specific for SLE diagnosis.", "protein": "Anti-Sm antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11535572" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation influences immunogenicity and pathogenicity.", "mechanism": "Autoantibodies to beta-2 glycoprotein 1 increase risk of thrombotic events such as stroke in APS.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "causal", "source_pmcid": "PMC11535572" }, { "confidence": "medium", "disease": "Neuropsychiatric SLE (NPSLE)", "glycan_involvement": "Glycosylation modulates antibody binding.", "mechanism": "Presence of anti-beta-2 glycoprotein 1 antibodies may indicate increased risk of neurovascular events in SLE.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535572" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation affects C3 stability and immune complex clearance.", "mechanism": "Low serum C3 is a marker of active SLE due to complement consumption in immune complex formation.", "protein": "Complement component C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 98, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49955PK", "G69834CE", "G95678HJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10471FG", "G10486CT", "G11115RO", "G14260UH", "G14972EH", "G15664MX", "G17208MA", "G20312EM", "G23294PN", "G23453IV", "G23719VF", "G26330YA", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G32104JU", "G33609NS", "G34029GR", "G34730YF", "G36442WJ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G42124LM", "G46503DX", "G46691LC", "G48414YA", "G49018RC", "G50282JC", "G55220VL", "G57317CE", "G57776ZU", "G59626AS", "G60145BJ", "G61302NC", "G62765YT", "G63041LO", "G64527OM", "G65000LJ", "G65184UU", "G66538GV", "G66676MI", "G67324HN", "G68490OW", "G70101JE", "G70160EA", "G70441OD", "G70619PT", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G76295SF", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84349RE", "G87661QW", "G90575OW", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G96091TT", "G96430BV", "G99679NM", "G22768VO", "G30769VJ", "G31544HA", "G70375MX", "G72398FA", "G78790NZ", "G86234IN", "G90093AU", "G43417UB", "G40702WU", "G49108TO", "G68668TB", "G83161QT" ], "uniprot_id": "P01024" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation modulates C4 function and immune response.", "mechanism": "Low C4 indicates complement activation and immune complex deposition in SLE.", "protein": "Complement component C4", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling ", "gene_name": "C4A", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G81006GJ", "G29931IJ", "G43417UB", "G74722FL", "G00912UN", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G22310AV", "G37868ZX", "G42358LZ", "G45495MK", "G48414YA", "G59626AS", "G64527OM", "G70101JE", "G71146HJ", "G75983OB", "G81263BG", "G82830MN", "G84452RH", "G88374WZ", "G49108TO", "G11870QZ", "G11911BT", "G14994KB", "G22768VO", "G50045TK", "G54612UD", "G63381RX", "G80223IX", "G83460ZZ", "G29068FM", "G01650EU", "G02815KT", "G05724UK", "G23294PN", "G31544HA", "G31852PQ", "G39188ZX", "G39619TI", "G41247ZX", "G46503DX", "G62765YT", "G62894KT", "G80920RR" ], "uniprot_id": "P0C0L4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered Fc N-glycosylation modulates IgG effector function and inflammation.", "mechanism": "Autoantibodies (IgG) form immune complexes, driving SLE pathology.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation affects IgM stability and immune complex formation.", "mechanism": "IgM autoantibodies may be protective or pathogenic in SLE.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation pattern changes reflect inflammation status.", "mechanism": "AGP is elevated in SLE as an acute phase reactant.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation impacts iron transport and immune modulation.", "mechanism": "Altered transferrin glycoforms may indicate anemia of chronic disease in SLE.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antioxidant activity and inflammation.", "mechanism": "Ceruloplasmin is an acute phase reactant elevated in SLE.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation modulates hemoglobin binding and clearance.", "mechanism": "Haptoglobin binds free hemoglobin, levels altered in SLE-related anemia.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects CRP's immune regulatory functions.", "mechanism": "CRP is an acute phase glycoprotein, often normal or mildly elevated in SLE.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "low", "disease": "Serositis", "glycan_involvement": "Glycosylation is essential for ligand binding and cell trafficking.", "mechanism": "E-selectin mediates leukocyte adhesion in inflamed serous tissues.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535589" }, { "confidence": "high", "disease": "Neuropsychiatric lupus", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects its antigenicity and autoantibody binding.", "mechanism": "Presence of anti-beta-2 glycoprotein I antibodies is associated with neuropsychiatric manifestations in lupus.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "high", "disease": "Neuropsychiatric lupus", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation modulates immune recognition.", "mechanism": "Lupus anticoagulant positivity is linked to increased risk of neuropsychiatric symptoms via vascular involvement.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Some nuclear antigens are glycoproteins; glycosylation may affect autoantigenicity.", "mechanism": "ANA positivity is a hallmark of SLE and neuropsychiatric lupus.", "protein": "Anti-nuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "medium", "disease": "Neuropsychiatric lupus", "glycan_involvement": "SS-A is a glycoprotein; glycosylation influences immune recognition.", "mechanism": "Anti-SS-A antibodies are associated with neuropsychiatric and systemic lupus features.", "protein": "SS-A (Ro) antigen", "protein_enriched": { "function": "RNA-binding protein that binds to misfolded non-coding RNAs, pre-5S rRNA, and several small cytoplasmic RNA molecules known as Y RNAs (PubMed:18056422, PubMed:26382853). Binds to endogenous Alu retroe", "gene_name": "RO60", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P10155" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "medium", "disease": "Neuropsychiatric lupus", "glycan_involvement": "Likely glycosylated; glycan structures may affect antigenicity.", "mechanism": "Anti-SS-A52 antibodies detected in neuropsychiatric lupus.", "protein": "SS-A52 antigen", "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "TPO is a glycoprotein; glycosylation affects immune response.", "mechanism": "Anti-TPO antibodies are present in SLE, indicating autoimmune overlap.", "protein": "Anti-TPO (thyroid peroxidase)", "protein_enriched": { "function": "Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4)", "gene_name": "TPO", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07202" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Chromatin-associated proteins may be glycosylated, influencing autoantigenicity.", "mechanism": "Anti-chromatin antibodies are associated with SLE activity.", "protein": "Chromatin", "relationship_type": "biomarker", "source_pmcid": "PMC11535612" }, { "confidence": "high", "disease": "renal thrombotic microangiopathy (TMA)", "glycan_involvement": "\u03b22GPI is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-\u03b22GPI antibodies promote TMA via complement activation and intraglomerular thrombosis.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS) nephropathy", "glycan_involvement": "Glycosylation of \u03b22GPI influences immune recognition.", "mechanism": "Anti-\u03b22GPI antibody positivity increases risk of APS nephropathy and TMA.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "biomarker", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "renal thrombotic microangiopathy (TMA)", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation may modulate antigenicity.", "mechanism": "aCL antibodies associated with intraglomerular microthrombi formation in lupus nephritis with TMA.", "protein": "anticardiolipin antibody (aCL)", "relationship_type": "causal", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "APS nephropathy", "glycan_involvement": "Targets glycoproteins involved in coagulation; glycosylation may affect epitope exposure.", "mechanism": "Lupus anticoagulant most associated with APS nephropathy and TMA.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC11535624" }, { "confidence": "medium", "disease": "chronic kidney disease", "glycan_involvement": "Glycosylation of \u03b22GPI may affect pathogenicity of autoantibodies.", "mechanism": "Triple aPL positivity (including anti-\u03b22GPI) linked to progression to chronic kidney disease in lupus nephritis with TMA.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "lupus nephritis", "glycan_involvement": "Targets glycoproteins; glycosylation may influence immune response.", "mechanism": "aCL antibodies are commonly present in lupus nephritis with TMA and indicate poor prognosis.", "protein": "anticardiolipin antibody (aCL)", "relationship_type": "biomarker", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "lupus nephritis", "glycan_involvement": "Glycosylation modulates \u03b22GPI antigenicity.", "mechanism": "Anti-\u03b22GPI antibody positivity increases risk of TMA in lupus nephritis.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "biomarker", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "renal thrombotic microangiopathy (TMA)", "glycan_involvement": "Targets glycoproteins in coagulation cascade.", "mechanism": "Lupus anticoagulant associated with intraglomerular microthrombi and poor renal prognosis.", "protein": "lupus anticoagulant", "relationship_type": "causal", "source_pmcid": "PMC11535624" }, { "confidence": "medium", "disease": "renal thrombotic microangiopathy (TMA)", "glycan_involvement": "Glycosylation may affect complement activation and antibody binding.", "mechanism": "Complement inhibition (e.g., eculizumab) can reduce anti-\u03b22GPI-induced TMA lesions.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11535624" }, { "confidence": "medium", "disease": "APS nephropathy", "glycan_involvement": "Domain-specific glycosylation may influence antibody specificity.", "mechanism": "Domain profiling of anti-\u03b22GPI antibodies correlates with APS nephropathy risk.", "protein": "beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "biomarker", "source_pmcid": "PMC11535624" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Low C4 levels indicate complement activation and consumption in SLE.", "protein": "C4 complement component", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 glycosylation modulates immune complex clearance.", "mechanism": "C3 levels are monitored for disease activity; normal C3 may indicate less active complement consumption.", "protein": "C3 complement component", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "high", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are associated with antiphospholipid syndrome and thrombosis risk.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Albumin glycosylation can affect renal handling and immune recognition.", "mechanism": "Hypoalbuminaemia reflects proteinuria and renal dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation is essential for inhibitor function.", "mechanism": "Deficiency excluded in differential diagnosis; normal levels help rule out hereditary angioedema.", "protein": "C1 esterase inhibitor", "protein_enriched": { "function": "Serine protease inhibitor, which acrs as a regulator of the classical complement pathway (PubMed:10946292, PubMed:11527969, PubMed:3458172, PubMed:6416294). Forms a proteolytically inactive stoichiome", "gene_name": "SERPING1", "glycan_count": 180, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G53434XO", "G43417UB", "G57321FI", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G04854VP", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G12580WI", "G14972EH", "G20528HD", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28681TP", "G31852PQ", "G34989PA", "G35107SO", "G35253PZ", "G36379GD", "G38663NM", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43089EG", "G43223CG", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47518TP", "G47644PP", "G48414YA", "G57317CE", "G57776ZS", "G57776ZU", "G59626AS", "G62765YT", "G64409MC", "G64527OM", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G73291XG", "G75983OB", "G76295SF", "G77669RF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G85740DB", "G86880BF", "G87123QX", "G89045VA", "G90382BL", "G90659AW", "G91636VS", "G92050GC", "G92135MA", "G92275SC", "G92551JA", "G93718GY", "G94470IW", "G95865ZB", "G02528FI", "G03644CB", "G04657PL", "G05962QB", "G11911BT", "G15169WU", "G18589KA", "G18804KX", "G22310AV", "G29299MO", "G30221QT", "G30740WO", "G31986NC", "G32788FZ", "G33791AF", "G35541EV", "G37399XV", "G40834TG", "G43669FQ", "G47748JZ", "G49018RC", "G51413EV", "G51653BI", "G52527GH", "G53075ES", "G54010QB", "G55132BD", "G55412XP", "G56518TU", "G56784JY", "G58087IP", "G59324HL", "G69521XL", "G71146HJ", "G72747WU", "G81637OR", "G82443XX", "G82830MN", "G86500WE", "G86795LJ", "G87399DK", "G88374WZ", "G92081HT", "G94917XT", "G98611JV", "G99668VU", "G14994KB", "G26198JI", "G36670VW", "G50045TK", "G53635BG", "G85144OK", "G91473PK", "G29068FM", "G58001LT", "G01521EA", "G15664MX", "G20706XG", "G22140GZ", "G34029GR", "G37692EO", "G47737VJ", "G49642SA", "G60923RB", "G61256FT", "G67164EE", "G98129XB", "G25278BX", "G47448YK", "G74722FL", "G07810QS", "G11115RO", "G13910DJ", "G17208MA", "G30248BL", "G44211QA", "G50856PC", "G55216FT", "G64751KD", "G65000LJ", "G65414LI", "G66088HZ", "G66537LK", "G66760KM", "G75006KF", "G75607BQ", "G90787TS", "G94665LC", "G99679NM" ], "uniprot_id": "P05155" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "Negative anti-\u03b22-glycoprotein I antibodies help exclude antiphospholipid syndrome in SLE.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "high", "disease": "Lupus nephritis", "glycan_involvement": "Glycosylation affects complement activation.", "mechanism": "Low C4 is associated with active lupus nephritis.", "protein": "C4 complement component", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Lupus nephritis", "glycan_involvement": "Glycosylation may influence filtration and immune interactions.", "mechanism": "Albuminuria is a marker of glomerular damage in lupus nephritis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Lupus nephritis", "glycan_involvement": "Glycosylation modulates complement activity.", "mechanism": "C3 levels reflect complement activation in lupus nephritis.", "protein": "C3 complement component", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antibody recognition.", "mechanism": "Negative anti-\u03b22-glycoprotein I antibodies suggest absence of antiphospholipid syndrome in SLE.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11535634" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Beta-2-glycoprotein-1 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2-glycoprotein-1 are diagnostic for APS and associated with increased thrombotic risk.", "protein": "beta-2-glycoprotein-1", "relationship_type": "biomarker", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "dural venous sinus thrombosis (DVST)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies to beta-2-glycoprotein-1 increase thrombotic risk, contributing to DVST.", "protein": "beta-2-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "pulmonary embolism (PE)", "glycan_involvement": "Glycosylation may affect protein function and immune response.", "mechanism": "Presence of anti-beta-2-glycoprotein-1 antibodies increases risk of PE via prothrombotic mechanisms.", "protein": "beta-2-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "varicella zoster virus (VZV) infection", "glycan_involvement": "Not specified.", "mechanism": "VZV infection can transiently induce anti-beta-2-glycoprotein-1 antibodies.", "protein": "beta-2-glycoprotein-1", "relationship_type": "biomarker", "source_pmcid": "PMC11535644" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Target is a glycoprotein; glycosylation may affect epitope exposure.", "mechanism": "Anticardiolipin antibodies are diagnostic for APS and indicate thrombotic risk.", "protein": "anticardiolipin antibody (targets beta-2-glycoprotein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "dural venous sinus thrombosis (DVST)", "glycan_involvement": "Target glycoprotein's glycosylation may modulate antibody binding.", "mechanism": "Anticardiolipin antibodies increase risk of thrombosis, including DVST.", "protein": "anticardiolipin antibody (targets beta-2-glycoprotein-1)", "relationship_type": "causal", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "pulmonary embolism (PE)", "glycan_involvement": "Target glycoprotein's glycosylation may modulate antibody binding.", "mechanism": "Anticardiolipin antibodies are associated with increased risk of PE.", "protein": "anticardiolipin antibody (targets beta-2-glycoprotein-1)", "relationship_type": "causal", "source_pmcid": "PMC11535644" }, { "confidence": "medium", "disease": "varicella zoster virus (VZV) infection", "glycan_involvement": "Not specified.", "mechanism": "VZV infection can transiently induce anticardiolipin antibodies.", "protein": "anticardiolipin antibody (targets beta-2-glycoprotein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11535644" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "O-mannosylation is essential for alpha-dystroglycan receptor function.", "mechanism": "Defective O-mannosyl glycosylation impairs alpha-dystroglycan function in muscle.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Qualitative or quantitative defects of alpha-dystroglycan", "glycan_involvement": "Glycosylation defects reduce ligand binding and muscle integrity.", "mechanism": "Mutations in DAG1 disrupt glycosylation and function of alpha-dystroglycan.", "protein": "DAG1", "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Myopathy caused by variation in POMT1", "glycan_involvement": "Defective O-mannosylation of alpha-dystroglycan.", "mechanism": "Loss of O-mannosyltransferase activity impairs alpha-dystroglycan glycosylation.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Myopathy caused by variation in POMT2", "glycan_involvement": "Defective O-mannosylation of alpha-dystroglycan.", "mechanism": "Loss of O-mannosyltransferase activity impairs alpha-dystroglycan glycosylation.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Myopathy caused by variation in POMGNT1", "glycan_involvement": "Impaired O-mannosyl glycan extension on alpha-dystroglycan.", "mechanism": "Defective O-linked glycosylation of alpha-dystroglycan due to POMGNT1 mutations.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "Defective glycan synthesis on alpha-dystroglycan.", "mechanism": "FKTN mutations disrupt glycosylation of alpha-dystroglycan.", "protein": "FKTN", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis", "gene_name": "CTSF", "glycan_count": 21, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G27058EU", "G41071NU", "G45395BF", "G58954YZ", "G62765YT", "G72667IM", "G75983OB", "G80920RR", "G83460ZZ", "G92050GC", "G92275SC", "G02815KT", "G23505EP", "G27126ED", "G28681TP", "G31852PQ", "G39188ZX", "G41247ZX", "G73430PD", "G80510PV" ], "uniprot_id": "Q9UBX1" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "Defective glycan synthesis on alpha-dystroglycan.", "mechanism": "FKRP mutations impair glycosylation of alpha-dystroglycan.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "Impaired O-mannosylation of alpha-dystroglycan.", "mechanism": "GMPPB mutations reduce GDP-mannose supply for glycosylation.", "protein": "GMPPB", "protein_enriched": { "function": "Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, diff", "gene_name": "DDR1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q08345" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy", "glycan_involvement": "Impaired glycan structure on alpha-dystroglycan.", "mechanism": "CRPPA mutations disrupt CDP-ribitol synthesis for glycan modification.", "protein": "CRPPA (ISPD)", "protein_enriched": { "function": "Involved in endoplasmic reticulum-associated degradation (ERAD). Accelerates the glycoprotein ERAD by proteasomes, by catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 in the N-glycans (PubM", "gene_name": "EDEM3", "glycan_count": 11, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G05724UK", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G80920RR", "G89045VA", "G49108TO" ], "uniprot_id": "Q9BZQ6" }, "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Collagen VI-related myopathy (Bethlem/Ullrich/LGMD spectrum)", "glycan_involvement": "Collagen VI is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Mutations affect collagen VI assembly and muscle extracellular matrix.", "protein": "Collagen VI (COL6A1, COL6A2, COL6A3)", "relationship_type": "causal", "source_pmcid": "PMC11537137" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "O-mannosylation of DG is essential for muscle structure/function.", "mechanism": "Mutations or reduced glycosylation of DG disrupt muscle attachment and integrity.", "protein": "Dystroglycan (DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "DNRX facilitates DG O-mannosylation via glycosyltransferase complex.", "mechanism": "DNRX deficiency reduces DG glycosylation, leading to muscle defects similar to DG mutants.", "protein": "Neurexin (DNRX)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "medium", "disease": "Autism spectrum disorders (ASDs)", "glycan_involvement": "Potential indirect link via DG glycosylation.", "mechanism": "DNRX is genetically associated with ASDs; muscle expression may link neuromuscular and neurodevelopmental phenotypes.", "protein": "Neurexin (DNRX)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "Defective O-mannosylation impairs DG function.", "mechanism": "Aberrant glycosylation of \u03b1-DG underlies dystroglycanopathies.", "protein": "Dystroglycan (DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Initiates O-mannosylation of DG.", "mechanism": "RT mutation impairs DG mannosylation, causing muscle attachment and contraction defects.", "protein": "Rotated Abdomen (RT, POMT1 homolog)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Initiates O-mannosylation of DG.", "mechanism": "TW mutation impairs DG mannosylation, causing muscle attachment and contraction defects.", "protein": "Twisted (TW, POMT2 homolog)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Limb Girdle Muscular Dystrophy", "glycan_involvement": "O-mannosylation required for DG function.", "mechanism": "Mutations in DG or its glycosylation pathway cause severe muscular dystrophy.", "protein": "Dystroglycan (DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation status affects DG stability.", "mechanism": "DG is part of the Dystrophin-Glycoprotein Complex; its dysfunction is implicated in DMD.", "protein": "Dystroglycan (DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11550397" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Laminin binds glycosylated DG for membrane stability.", "mechanism": "Knockdown of Laminin in muscle leads to defects in muscle morphology and function.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "DNRX bridges DG to O-mannosyltransferase complex for glycosylation.", "mechanism": "DNRX deficiency impairs DG glycosylation, phenocopying dystroglycanopathy muscle defects.", "protein": "Neurexin (DNRX)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11550397" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Transmembrane glycoprotein; activation via regulated intramembrane proteolysis.", "mechanism": "Upregulates CCR2, CCR1, and MMP-9, promoting monocyte chemotaxis and VSMC migration.", "protein": "CREB3", "protein_enriched": { "function": "Binds DNA as a heterodimer with MLX/TCFL4 and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involv", "gene_name": "MLXIPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP71" }, "relationship_type": "causal", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoprotein structure required for ER/Golgi localization and activation.", "mechanism": "Reduced CREB3 protects against HFD-induced weight gain and hyperglycemia.", "protein": "CREB3", "protein_enriched": { "function": "Binds DNA as a heterodimer with MLX/TCFL4 and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involv", "gene_name": "MLXIPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP71" }, "relationship_type": "causal", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "Transmembrane glycoprotein; activation and nuclear translocation depend on glycosylation.", "mechanism": "Activates ApoA-IV gene, increasing peripheral fatty acid uptake and promoting hepatic lipid accumulation.", "protein": "CREB3", "protein_enriched": { "function": "Binds DNA as a heterodimer with MLX/TCFL4 and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involv", "gene_name": "MLXIPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP71" }, "relationship_type": "causal", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation regulates CREB3L3 activation and transcriptional activity.", "mechanism": "Promotes apolipoprotein (ApoA-IV, ApoA-V, ApoC-II) expression, enhances TG clearance, inhibits SREBP activation.", "protein": "CREB3L3", "protein_enriched": { "function": "Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-bindi", "gene_name": "CREB3L1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G57321FI", "G62765YT", "G41247ZX" ], "uniprot_id": "Q96BA8" }, "relationship_type": "protective", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "N-glycosylation modulates secretion and activity.", "mechanism": "Secreted CREB3L3-C inhibits ANGPTL3-ANGPTL8 complex formation, increasing LPL activity and reducing plasma TG.", "protein": "CREB3L3", "protein_enriched": { "function": "Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-bindi", "gene_name": "CREB3L1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G57321FI", "G62765YT", "G41247ZX" ], "uniprot_id": "Q96BA8" }, "relationship_type": "protective", "source_pmcid": "PMC11586310" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Promotes SIRT3 expression, reducing oxidative stress and NLRP3 inflammasome activation.", "protein": "CREB3L3", "protein_enriched": { "function": "Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-bindi", "gene_name": "CREB3L1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G57321FI", "G62765YT", "G41247ZX" ], "uniprot_id": "Q96BA8" }, "relationship_type": "protective", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation affects nuclear translocation and transcriptional activity.", "mechanism": "Activates gluconeogenic genes (PEPCK, G6Pase), regulates fasting glucose; knockdown reduces hyperglycemia.", "protein": "CREB3L3", "protein_enriched": { "function": "Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-bindi", "gene_name": "CREB3L1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G57321FI", "G62765YT", "G41247ZX" ], "uniprot_id": "Q96BA8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CRP is a secreted glycoprotein; glycosylation essential for stability and function.", "mechanism": "CREB3L3 upregulates CRP during inflammation, serving as a marker and mediator of cardiovascular risk.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11586310" }, { "confidence": "medium", "disease": "Myocardial Ischemia\u2013Reperfusion Injury", "glycan_involvement": "Regulates O-GlcNAcylation of proteins via HBP pathway.", "mechanism": "Upregulates GFPT1, enhancing HBP flux and O-GlcNAc modification, increasing cardiomyocyte survival.", "protein": "CREB3L4", "protein_enriched": { "function": "Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity ", "gene_name": "CMAS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8NFW8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11586310" }, { "confidence": "medium", "disease": "Obesity/Diabetes Mellitus", "glycan_involvement": "Transmembrane glycoprotein; glycosylation required for ER/Golgi function.", "mechanism": "Regulates adipocyte differentiation; knockout improves glucose tolerance and insulin sensitivity.", "protein": "CREB3L4", "protein_enriched": { "function": "Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity ", "gene_name": "CMAS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8NFW8" }, "relationship_type": "protective", "source_pmcid": "PMC11586310" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and aggregation propensity.", "mechanism": "APP processing leads to amyloid beta aggregation and neurodegeneration.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "O-glycosylation modulates aggregation and toxicity.", "mechanism": "Mutant alpha-synuclein aggregates cause dopaminergic neuron loss.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "N-glycosylation required for CFTR folding and trafficking.", "mechanism": "CFTR mutations disrupt chloride transport and mucus viscosity.", "protein": "Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)", "protein_enriched": { "function": "Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the ", "gene_name": "CFTR", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P13569" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation influences dystrophin stability and membrane association.", "mechanism": "Dystrophin mutations lead to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Huntington's disease", "glycan_involvement": "O-glycosylation may affect huntingtin aggregation and toxicity.", "mechanism": "Mutant huntingtin protein aggregates and causes neuronal death.", "protein": "Huntingtin", "protein_enriched": { "function": "May play a role in microtubule-mediated transport or vesicle function", "gene_name": "HTT", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G00912UN", "G26330YA", "G45395BF" ], "uniprot_id": "P42858" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation may modulate SOD1 stability and aggregation.", "mechanism": "Mutant SOD1 forms toxic aggregates leading to motor neuron degeneration.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "O-glycosylation may influence TDP-43 aggregation.", "mechanism": "TDP-43 aggregation disrupts RNA metabolism and neuronal function.", "protein": "TAR DNA-binding protein 43 (TDP-43)", "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Spinocerebellar ataxias (SCAs)", "glycan_involvement": "Glycosylation may affect protein aggregation and toxicity.", "mechanism": "Mutant ataxin-1 aggregates cause cerebellar degeneration.", "protein": "Ataxin-1", "protein_enriched": { "function": "Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-m", "gene_name": "ATXN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54253" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Spinocerebellar ataxias (SCAs)", "glycan_involvement": "Glycosylation may modulate aggregation propensity.", "mechanism": "Mutant ataxin-3 forms toxic aggregates in neurons.", "protein": "Ataxin-3", "protein_enriched": { "function": "Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:16118", "gene_name": "ATXN3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54252" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "medium", "disease": "Spinocerebellar ataxias (SCAs)", "glycan_involvement": "Glycosylation may influence protein stability.", "mechanism": "Mutant ataxin-7 disrupts protein degradation and mitochondrial function.", "protein": "Ataxin-7", "protein_enriched": { "function": "Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex (PubMed:15932940, PubMed:18206972). Mediates the interaction of SAGA complex with the CRX and is involved in CRX-depen", "gene_name": "ATXN7", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O15265" }, "relationship_type": "causal", "source_pmcid": "PMC11594678" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Core fucosylation of N-glycans at Asn630 and Asn432 is measured to diagnose CDG.", "mechanism": "Altered glycosylation profile of transferrin reflects defects in N-glycan synthesis and fucosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "high", "disease": "FUT8-CDG", "glycan_involvement": "Absence of core fucose on N-glycans at Asn630.", "mechanism": "Complete loss of core fucosylation on transferrin indicates FUT8 enzyme deficiency.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "high", "disease": "SLC35C1-CDG (CDG-IIc/LAD2)", "glycan_involvement": "No core-fucosylated glycans detected at Asn630.", "mechanism": "Defective GDP-fucose transporter leads to nearly null core fucosylation on transferrin.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "high", "disease": "GFUS-CDG", "glycan_involvement": "Reduced core fucosylation at Asn630.", "mechanism": "Defective GDP-fucose synthesis reduces core fucosylation on transferrin to one-third of normal.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "medium", "disease": "FCSK-CDG", "glycan_involvement": "Altered core fucosylation at Asn630.", "mechanism": "Impaired fucose salvage pathway affects core fucosylation of transferrin.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "medium", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Fucosylation of N-glycans on IgG is high in healthy individuals, altered in CDG.", "mechanism": "IgG is a major source of serum N-glycans, and its fucosylation profile reflects glycosylation status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11604788" }, { "confidence": "medium", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Core fucosylation levels on transferrin are measured pre- and post-treatment.", "mechanism": "Quantification of transferrin fucosylation is used to monitor efficacy of monosaccharide supplementation therapy.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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"G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11604788" }, { "confidence": "high", "disease": "MAN1B1-congenital disorder of glycosylation (MAN1B1-CDG, Rafiq syndrome, MRT15)", "glycan_involvement": "Defective N-glycan trimming results in accumulation of mannose-rich glycans and decreased N-acetylglucosamine-linked glycans.", "mechanism": "Loss-of-function variants in MAN1B1 disrupt ER N-glycan processing, leading to abnormal glycoprotein maturation.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "Global disruption of protein glycosylation affects neuronal development and function.", "mechanism": "Impaired glycoprotein folding and trafficking in neural tissues due to defective N-glycosylation.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "medium", "disease": "Musculoskeletal abnormalities", "glycan_involvement": "Altered N-glycan structures on structural glycoproteins.", "mechanism": "Abnormal glycosylation affects extracellular matrix proteins and signaling pathways involved in musculoskeletal development.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "medium", "disease": "Facial dysmorphism", "glycan_involvement": "Defective N-glycan processing on key morphogenetic glycoproteins.", "mechanism": "Disrupted glycosylation of developmental proteins leads to abnormal craniofacial morphogenesis.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "low", "disease": "Truncal obesity", "glycan_involvement": "Abnormal glycoprotein signaling in metabolic pathways.", "mechanism": "Altered glycosylation may affect metabolic signaling and adipose tissue regulation.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "low", "disease": "Muscular hypotonia", "glycan_involvement": "Impaired N-glycan maturation on muscle and neuronal glycoproteins.", "mechanism": "Defective glycosylation impacts muscle protein function and neuromuscular junctions.", "protein": "MAN1B1 (ER mannosyl-oligosaccharide 1,2-alpha-mannosidase)", "relationship_type": "causal", "source_pmcid": "PMC11609710" }, { "confidence": "high", "disease": "Becker Muscular Dystrophy", "glycan_involvement": "Dystrophin interacts with glycoproteins in the dystrophin-glycoprotein complex, which are glycosylated and mediate membrane stability.", "mechanism": "Mutations in dystrophin gene disrupt the dystrophin-glycoprotein complex, leading to muscle cell instability and degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11618128" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of complex components is essential for membrane-cytoskeleton linkage; disruption affects cardiac tissue integrity.", "mechanism": "Loss of dystrophin-glycoprotein complex function in cardiac myocytes leads to membrane instability, cell loss, and progressive cardiac dilation.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11618128" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycoprotein complex disruption impairs glycan-mediated signaling and mechanical stability.", "mechanism": "Degeneration of cardiac muscle due to dystrophin deficiency results in impaired contractility and heart failure.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11618128" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation of complex components may affect electrical conduction properties.", "mechanism": "Degeneration and fibrosis of cardiac conduction system due to dystrophin-glycoprotein complex loss leads to arrhythmias.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11618128" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy", "glycan_involvement": "Glycosylation status of complex components influences cardiac muscle structure.", "mechanism": "Early cardiac hypertrophy in BMD may progress to dilated cardiomyopathy due to dystrophin complex dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11618128" }, { "confidence": "high", "disease": "Mucosal barrier dysfunction", "glycan_involvement": "O-glycosylation is essential for mucin structure and barrier properties.", "mechanism": "Degradation of mucin O-glycans by gut microbes can thin the mucus layer, compromising barrier function.", "protein": "Mucin (O-glycosylated glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "high", "disease": "Healthy gut state", "glycan_involvement": "Enzymatic cleavage of mucin O-glycans supports beneficial cross-feeding.", "mechanism": "A. muciniphila abundance and mucin degradation are associated with gut health and metabolic benefits.", "protein": "Akkermansia muciniphila mucin-degrading enzymes", "relationship_type": "protective", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Ruminococcus-associated disease state", "glycan_involvement": "Aggressive mucin O-glycan degradation may promote dysbiosis.", "mechanism": "High Ruminococcus abundance is associated with disease states and mucosal barrier disruption.", "protein": "Ruminococcus spp. mucin-degrading enzymes", "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Mucosal barrier dysfunction", "glycan_involvement": "Desulfation of O-glycans exposes mucin to further enzymatic attack.", "mechanism": "BT1636 removes sulfate from mucin O-glycans, facilitating further degradation and potential barrier compromise.", "protein": "Bacteroides thetaiotaomicron sulfatase BT1636", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8A789" }, "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Healthy gut state", "glycan_involvement": "Cleavage of terminal fucose from mucin O-glycans.", "mechanism": "Fucosidase activity enables cross-feeding and SCFA production, supporting gut health.", "protein": "Akkermansia muciniphila fucosidase Amuc_0392", "relationship_type": "protective", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Removal of sialic acid from O-glycans alters mucin structure.", "mechanism": "Altered sialidase activity can change mucin glycan exposure, affecting microbial colonization.", "protein": "Akkermansia muciniphila sialidases Amuc_0625, Amuc_1835", "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Changes in O-glycosylation patterns.", "mechanism": "Altered mucin O-glycan composition is observed in IBD patients.", "protein": "Mucin O-glycan core structures", "relationship_type": "biomarker", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Changes in N-glycan branching and composition.", "mechanism": "Altered N-glycosylation of mucins is associated with tumorigenesis.", "protein": "Mucin N-glycan structures", "relationship_type": "biomarker", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Short-chain fatty acid deficiency", "glycan_involvement": "Utilize released mucin monosaccharides for SCFA synthesis.", "mechanism": "Dependence on mucin degradation for butyrate production; loss leads to SCFA deficiency.", "protein": "Secondary degraders (e.g. Faecalibacterium duncaniae)", "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "medium", "disease": "Sulfate-reducing bacteria overgrowth", "glycan_involvement": "Utilizes sulfate released from mucin O-glycans.", "mechanism": "Overgrowth can lead to excess hydrogen sulfide, implicated in gut inflammation.", "protein": "Desulfovibrio piger (sulfate reduction enzymes)", "relationship_type": "causal", "source_pmcid": "PMC11632381" }, { "confidence": "high", "disease": "Human tumors (e.g., brain tumors, colorectal cancer)", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Promotes S phase entry and cell cycle progression via activation of PI3K/Akt/mTOR pathway and upregulation of cyclin E/Cdk2, contributing to cell transformation.", "protein": "JC virus small tumor antigen (Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "high", "disease": "Human tumors (e.g., brain tumors, colorectal cancer)", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Inactivates tumor suppressors p53 and pRb, leading to dysregulated cell cycle and transformation.", "protein": "JC virus large T antigen (LT-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "Progressive multifocal leukoencephalopathy (PML)", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "JCV infection and expression of early proteins (including Sm t-Ag) are associated with PML in immunocompromised individuals.", "protein": "JC virus small tumor antigen (Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "BK virus-associated nephropathy (BKVAN)", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "BKPyV infection and expression of early proteins contribute to nephropathy in transplant patients.", "protein": "BK virus small tumor antigen (BKPyV Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "Human tumors", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "BKPyV genome integration and early protein expression associated with human tumors.", "protein": "BK virus small tumor antigen (BKPyV Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "high", "disease": "Merkel cell carcinoma", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "MCPyV Sm t-Ag expression is strongly associated with tumor induction and transformation.", "protein": "Merkel cell polyomavirus small tumor antigen (MCPyV Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "Trichodysplasia spinulosa", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "TSPyV infection and early protein expression cause trichodysplasia spinulosa.", "protein": "Trichodysplasia spinulosa-associated polyomavirus (TSPyV) Sm t-Ag", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "Human tumors", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Sm t-Ag activates growth-promoting pathways (PI3K/Akt/mTOR), suggesting potential as a therapeutic target.", "protein": "JC virus small tumor antigen (Sm t-Ag)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11647237" }, { "confidence": "medium", "disease": "Human tumors", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Detection of Sm t-Ag expression may indicate JCV involvement in tumorigenesis.", "protein": "JC virus small tumor antigen (Sm t-Ag)", "relationship_type": "biomarker", "source_pmcid": "PMC11647237" }, { "confidence": "low", "disease": "Human tumors", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Sm t-Ag interacts with translation elongation factor eEF1A, potentially enhancing protein synthesis and cell proliferation.", "protein": "JC virus small tumor antigen (Sm t-Ag)", "relationship_type": "causal", "source_pmcid": "PMC11647237" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b2-dystroglycan is a glycoprotein; its glycosylation is essential for membrane localization and interaction with dystrophin.", "mechanism": "Loss of dystrophin destabilizes \u03b2-dystroglycan, causing its removal from the sarcolemma and contributing to muscle pathology.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin itself is not glycosylated, but its function depends on interaction with glycosylated \u03b2-dystroglycan.", "mechanism": "Loss-of-function mutations in dystrophin gene cause DMD by disrupting the dystrophin-associated glycoprotein complex.", "protein": "dystrophin", "relationship_type": "causal", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation of \u03b2-dystroglycan is required for its stabilization and function in the dystrophin-associated glycoprotein complex.", "mechanism": "Restoration of dystrophin reading frame (via gene editing) stabilizes \u03b2-dystroglycan at the sarcolemma, resembling BMD phenotype.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "protective", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Truncated dystrophin retains ability to interact with glycosylated \u03b2-dystroglycan.", "mechanism": "In-frame deletions in dystrophin gene produce truncated but partially functional dystrophin, leading to milder BMD.", "protein": "dystrophin", "relationship_type": "causal", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation status affects \u03b2-dystroglycan stability and detection.", "mechanism": "Reduced \u03b2-dystroglycan at the sarcolemma is a marker of dystrophin deficiency in DMD muscle cells.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Therapeutic benefit depends on proper glycosylation of \u03b2-dystroglycan for membrane localization.", "mechanism": "Gene editing that restores dystrophin stabilizes \u03b2-dystroglycan, suggesting its role as a therapeutic endpoint.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restored dystrophin enables interaction with glycosylated \u03b2-dystroglycan.", "mechanism": "Prime editing restores dystrophin synthesis, rescuing muscle cell function.", "protein": "dystrophin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation is necessary for \u03b2-dystroglycan's interaction with dystrophin.", "mechanism": "Proximity ligation assays detect dystrophin-\u03b2-dystroglycan interaction as evidence of successful gene repair.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation is critical for \u03b2-dystroglycan's membrane stability.", "mechanism": "In absence of dystrophin, \u03b2-dystroglycan is destabilized and vacates the plasma membrane, contributing to muscle degeneration.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restored dystrophin function depends on interaction with glycosylated \u03b2-dystroglycan.", "mechanism": "Gene editing approaches (prime editing) restore dystrophin and dystrophin-\u03b2-dystroglycan linkages, rescuing muscle cell phenotype.", "protein": "dystrophin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11648982" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "O-glycosylation may affect aggregation and toxicity.", "mechanism": "Oligomerized alpha-synuclein forms pathological plaques leading to neurodegeneration.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11654704" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation of viral envelope glycoproteins modulates immunogenicity and cell entry.", "mechanism": "Expressed by oncolytic HSV-1 virus to enhance tumor cell lysis and immune response.", "protein": "Envelope glycoprotein (Gibbon-ape leukemia virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "high", "disease": "Renal-cell carcinoma", "glycan_involvement": "N-glycosylation may regulate CD70 stability and immune recognition.", "mechanism": "CD70 is overexpressed on tumor cells and targeted by CAR-T cells.", "protein": "CD70", "protein_enriched": { "function": "Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells (PubMed:28011863, PubMed:28011864, PubMed:8387892). The CD7", "gene_name": "CD70", "glycan_count": 16, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G06247RL", "G08918WF", "G27058EU", "G29299MO", "G40574BA", "G45395BF", "G57776ZS", "G63041LO", "G69521XL", "G79666IR", "G41247ZX", "G57321FI", "G49108TO" ], "uniprot_id": "P32970" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Potential N-glycosylation may affect IDO activity and localization.", "mechanism": "IDO is overexpressed in tumors, suppressing T-cell responses; targeted by vaccine.", "protein": "Indoleamine 2,3-dioxygenase (IDO)", "protein_enriched": { "function": "Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contrib", "gene_name": "IDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14902" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "high", "disease": "Solid cancers", "glycan_involvement": "Glycosylation of IL-2 and IL-2R\u03b1 modulates receptor binding and immune activation.", "mechanism": "Recombinant IL-2 fused to IL-2R\u03b1 stimulates CD8+ and NK cells for antitumor activity.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "high", "disease": "Solid cancers", "glycan_involvement": "N-glycosylation of CD25 affects receptor expression and function.", "mechanism": "Fusion with IL-2 enhances selectivity for intermediate-affinity IL-2 receptor.", "protein": "IL-2 receptor alpha chain (CD25)", "protein_enriched": { "function": "Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreacti", "gene_name": "IL2RA", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G23505EP", "G25079LO" ], "uniprot_id": "P01589" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Glycosylation may regulate VISTA surface expression and immune modulation.", "mechanism": "VISTA is an immune checkpoint exploited by cancers to inhibit T-cell responses.", "protein": "VISTA", "protein_enriched": { "function": "Cell surface glycoprotein involved in various biological processes including angiogenesis, immune response modulation, and tissue remodeling and repair. Participates in pericyte proliferation through ", "gene_name": "CD248", "glycan_count": 5, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57317CE", "G49108TO" ], "uniprot_id": "Q9HCU0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "medium", "disease": "NSCLC and soft-tissue sarcoma", "glycan_involvement": "N-glycosylation of LAG-3 modulates ligand binding and checkpoint function.", "mechanism": "LAG-3 agonist enhances immune response and improves survival.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "medium", "disease": "Wilms Tumor", "glycan_involvement": "Potential glycosylation may affect antigen processing.", "mechanism": "WT1 peptide used to select and stimulate T cells for immunotherapy.", "protein": "WT1", "protein_enriched": { "function": "Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:17716689, PubMed:2525", "gene_name": "WT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19544" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "medium", "disease": "HPV-positive cancers", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "HPV E7 peptide used to select T cells for immunotherapy.", "protein": "HPV E7", "protein_enriched": { "function": "Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA rep", "gene_name": "E7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03129" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11654704" }, { "confidence": "high", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "No direct data on ATA glycosylation; total IgG galactosylation is reduced in SSc.", "mechanism": "Anti-TOP1 antibodies (ATA) are highly disease-specific and correlate with diffuse cutaneous SSc, higher mortality, and interstitial lung disease.", "protein": "Topoisomerase I (TOP1)", "protein_enriched": { "function": "Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-s", "gene_name": "TOP1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G46503DX", "G70441OD", "G49108TO" ], "uniprot_id": "P11387" }, "relationship_type": "biomarker", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "ACA-specific IgG1 shows decreased sialylation and bisecting galactosylation (limited data).", "mechanism": "Anti-centromere antibodies (ACA) are highly disease-specific, associated with limited cutaneous SSc, slower progression, and less severe microangiopathy.", "protein": "Centromere protein B (CENP-B)", "protein_enriched": { "function": "Interacts with centromeric heterochromatin in chromosomes and binds to a specific 17 bp subset of alphoid satellite DNA, called the CENP-B box (PubMed:11726497). May organize arrays of centromere sate", "gene_name": "CENPB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07199" }, "relationship_type": "biomarker", "source_pmcid": "PMC11659924" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Fc glycosylation may modulate immune complex activity, but not directly studied for ATA.", "mechanism": "ATA-TOP1 immune complexes can activate fibroblasts and monocytes, potentially contributing to inflammation and fibrosis.", "protein": "Topoisomerase I (TOP1)", "protein_enriched": { "function": "Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-s", "gene_name": "TOP1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G46503DX", "G70441OD", "G49108TO" ], "uniprot_id": "P11387" }, "relationship_type": "causal (suggested)", "source_pmcid": "PMC11659924" }, { "confidence": "low", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "ACA glycosylation may affect effector function; limited data.", "mechanism": "ACA may induce apoptosis in dermal fibroblasts in vitro; mechanism in vivo unclear.", "protein": "Centromere protein B (CENP-B)", "protein_enriched": { "function": "Interacts with centromeric heterochromatin in chromosomes and binds to a specific 17 bp subset of alphoid satellite DNA, called the CENP-B box (PubMed:11726497). May organize arrays of centromere sate", "gene_name": "CENPB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07199" }, "relationship_type": "causal (suggested)", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Reduced Fc galactosylation; functional impact on inflammation.", "mechanism": "Total IgG galactosylation is reduced in SSc, correlating with disease severity and skin fibrosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Reduced Fc galactosylation/sialylation enhances pro-inflammatory activity.", "mechanism": "Low Fc galactosylation and sialylation of IgG/ACPA associated with disease activity and progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Lower galactosylation/sialylation of IgG observed in AAV.", "mechanism": "Anti-MPO antibodies are directly pathogenic; passive transfer induces vasculitis in animal models.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "causal", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Reduced Fc galactosylation/sialylation in anti-PR3 IgG.", "mechanism": "Anti-PR3 antibodies are directly pathogenic; passive transfer induces vasculitis.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "causal", "source_pmcid": "PMC11659924" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Undersialylation of Fc region increases pro-inflammatory activity.", "mechanism": "Anti-histone IgG is less sialylated, possibly enhancing inflammation and apoptotic cell clearance.", "protein": "Histone", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "ACPA Fc glycosylation (low galactosylation/sialylation) enhances pathogenicity.", "mechanism": "Anti-citrullinated protein antibodies (ACPA) are highly specific for RA; immune complexes activate macrophages and complement.", "protein": "Citrullinated proteins", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11659924" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "Reduced sialylation (especially \u03b12,6-linked) impairs anti-inflammatory function and complement inhibition.", "mechanism": "Decreased sialylated N-glycans in IgG-Fc correlate with disease severity and therapeutic resistance.", "protein": "IgG-Fc", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "Global reduction in sialylated N-glycans reflects inflammatory pathophysiology and predicts therapeutic resistance.", "mechanism": "Lower levels of total and sialylated N-glycans are associated with CIDP diagnosis and poor response to IVIg.", "protein": "Serum total N-glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "\u03b12,6-linked sialylation promotes anti-inflammatory effects (M2 macrophage phenotype).", "mechanism": "Higher \u03b12,6-linked sialylation is associated with better IVIg response.", "protein": "Serum sialylated N-glycoproteins (\u03b12,6-linked)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Reduced O-glycosylation may contribute to impaired nerve repair and inflammation.", "mechanism": "Lower O-glycan levels are linked to resistance to therapy.", "protein": "Serum total O-glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "Demyelinating peripheral neuropathy", "glycan_involvement": "O-glycosylation is essential for normal myelin formation.", "mechanism": "Deficiency in O-GlcNAcylation in Schwann cells leads to abnormal myelin formation and neuropathy.", "protein": "Schwann cell glycoproteins (O-GlcNAcylation)", "relationship_type": "causal", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Not directly related to glycosylation in this context.", "mechanism": "Elevated serum NfL reflects axonal damage but does not predict short-term treatment response.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "HexNAc is a precursor for N-glycan branching; its reduction impairs anti-inflammatory glycan structures.", "mechanism": "Lower serum HexNAc correlates with disease severity.", "protein": "Serum HexNAc (N-acetylglucosamine)", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "Sialylation modulates IgG effector function.", "mechanism": "Sialylated N-glycans in IgG-Fc inhibit complement-mediated cytotoxicity.", "protein": "IgG-Fc", "relationship_type": "protective", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "CIDP variants/autoimmune nodopathies", "glycan_involvement": "Glycosylation status may affect antigenicity.", "mechanism": "Autoantibodies against these glycoproteins define CIDP variants.", "protein": "Contactin-1 (CNTN1), Neurofascin-155 (NF155), Caspr1", "relationship_type": "biomarker", "source_pmcid": "PMC11669748" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Loss of sialylation increases susceptibility to inflammation and demyelination.", "mechanism": "Sialic acid-rich glycoproteins modulate immune response via complement inhibition and microglial regulation.", "protein": "Peripheral nervous system glycoproteins (sialic acid-containing)", "relationship_type": "causal", "source_pmcid": "PMC11669748" }, { "confidence": "high", "disease": "Hereditary Fructose Intolerance (HFI)", "glycan_involvement": "N-glycosylation defect (hypoglycosylation) of transferrin", "mechanism": "Abnormal transferrin glycosylation patterns are observed in HFI due to secondary impairment of N-glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11672228" }, { "confidence": "high", "disease": "Hereditary Fructose Intolerance (HFI)", "glycan_involvement": "Reduced GDP-mannose and GDP-fucose, affecting N-glycosylation", "mechanism": "F1P accumulation in HFI inhibits MPI, leading to impaired N-glycosylation.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11672228" }, { "confidence": "high", "disease": "MPI-CDG (Congenital Disorder of Glycosylation type Ib)", "glycan_involvement": "Impaired synthesis of GDP-mannose for N-glycosylation", "mechanism": "Genetic defects in MPI cause primary N-glycosylation defects.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of 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It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11672228" }, { "confidence": "medium", "disease": "MPI-CDG (Congenital Disorder of Glycosylation type Ib)", "glycan_involvement": "N-glycosylation required for ICAM-1 function", "mechanism": "Mannose supplementation restores ICAM-1 expression in MPI-deficient mice.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). 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"G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11672228" }, { "confidence": "medium", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "Impaired N-glycosylation affects liver metabolism", "mechanism": "MPI deficiency (primary or secondary) leads to hepatic fat accumulation.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11672228" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Impaired N-glycosylation affects extracellular matrix and fibrosis", "mechanism": "MPI deficiency is associated with hepatic fibrosis in both HFI and MPI-CDG.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11672228" }, { "confidence": "high", "disease": "Hereditary Fructose Intolerance (HFI)", "glycan_involvement": "N-glycosylation defect", "mechanism": "Transferrin glycosylation patterns distinguish HFI from healthy controls.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11672228" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "AST is glycosylated, which may affect its stability and serum levels.", "mechanism": "Elevated AST levels reflect hepatocyte injury and fibrosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used to diagnose diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may influence AST secretion and detection.", "mechanism": "AST elevation is associated with NAFLD progression.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "AST and ALT are glycoproteins; glycosylation may affect their serum levels.", "mechanism": "FIB-4 combines age, AST, ALT, and platelet count to estimate fibrosis.", "protein": "FIB-4 panel", "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "AST glycosylation may impact APRI accuracy.", "mechanism": "APRI uses AST and platelet count to predict fibrosis.", "protein": "APRI panel", "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may affect AST half-life and detection.", "mechanism": "AST is elevated in advanced liver disease including cirrhosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycation of hemoglobin is a marker of chronic glucose exposure.", "mechanism": "Elevated HbA1c is associated with increased risk of liver fibrosis in diabetics.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Panel includes glycoproteins; glycosylation may affect biomarker performance.", "mechanism": "FIB-4 helps identify NAFLD patients at risk for fibrosis.", "protein": "FIB-4 panel", "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may modulate AST serum levels.", "mechanism": "Elevated AST may be seen in diabetics with liver involvement.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycation reflects metabolic dysfunction linked to NAFLD.", "mechanism": "Higher HbA1c may indicate increased risk of NAFLD.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11691340" }, { "confidence": "high", "disease": "Infective endocarditis", "glycan_involvement": "Cell wall rhamnose polysaccharide structure critical for adhesion and immune evasion.", "mechanism": "RGP mediates adhesion to endocardium via binding fibronectin, collagen, and laminin, triggers platelet aggregation, enhances virulence.", "protein": "Rhamnose glucose polymer (RGP)", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "Glucan synthesis via glycosylation of glucose residues.", "mechanism": "GTFs synthesize extracellular glucans, promoting biofilm formation and tooth surface adhesion.", "protein": "Glucosyltransferases (GTFs)", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "Cerebral hemorrhage", "glycan_involvement": "Adhesion to collagen glycoprotein; glycosylation status not specified.", "mechanism": "Cnm binds type I collagen in cerebral vessels, promotes endothelial invasion, inflammation, and hemorrhage.", "protein": "Collagen-binding protein Cnm", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Defective O-glycosylation of IgA1 implicated in pathogenesis.", "mechanism": "Cnm+ S. mutans aggregates in glomeruli, triggers IgA immune reactions and glycosylation defects in IgA1.", "protein": "Collagen-binding protein Cnm", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Adhesin glycoprotein interacts with host glycoproteins (gp340/DMBT1).", "mechanism": "PA mediates resistance to phagocytosis, prolongs bacteremia, increases inflammatory markers.", "protein": "Protein antigen (PA)", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "Infective endocarditis", "glycan_involvement": "Interaction with glycoprotein receptors and fibrinogen glycoprotein.", "mechanism": "Cbm binds type I collagen and fibrinogen, induces platelet aggregation via Glycoprotein IIb/IIIa receptor.", "protein": "Collagen-binding protein Cbm", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glucan synthesis modulates immune response.", "mechanism": "GTFs induce IL-6 production, promoting intestinal inflammation.", "protein": "Glucosyltransferases (GTFs)", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Adhesion to host fibronectin glycoprotein.", "mechanism": "Mediate adhesion to fibronectin and endothelial cells, increase resistance to phagocytosis, prolong bacteremia.", "protein": "Fibronectin-binding proteins (AtlA, RgpG, BrpA, Psr)", "relationship_type": "causal", "source_pmcid": "PMC11693680" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Host glycoprotein mediates bacterial exclusion.", "mechanism": "DMBT1 inhibits S. mutans adhesion to endothelial cells, reducing inflammation and vascular damage.", "protein": "DMBT1 (gp340)", "protein_enriched": { "function": "May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers. May play roles in mucosal defense system, cellular immune defense and epithelial di", "gene_name": "DMBT1", "glycan_count": 1, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q9UGM3" }, "relationship_type": "protective", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation defects in IgA1 are central to disease.", "mechanism": "Defective O-glycosylation of IgA1 leads to mesangial deposition and nephropathy.", "protein": "IgA1", "relationship_type": "biomarker", "source_pmcid": "PMC11693680" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and trafficking.", "mechanism": "Altered processing of platelet APP shifts balance toward amyloidogenic pathway, increasing A\u03b2 production and contributing to AD neuropathology.", "protein": "APP (Amyloid Beta Precursor Protein)", "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is a glycopeptide; glycosylation may affect aggregation and clearance.", "mechanism": "Platelet-derived A\u03b2 contributes to amyloid plaque formation in the brain, promoting neurodegeneration.", "protein": "A\u03b2 (Amyloid Beta Peptide)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ADAM10 is glycosylated, which affects its enzymatic activity and localization.", "mechanism": "ADAM10/\u03b1-secretase processing of APP produces neuroprotective sAPP\u03b1; reduced ADAM10 activity in platelets of AD patients shifts processing toward amyloidogenic pathway.", "protein": "ADAM10", "relationship_type": "protective", "source_pmcid": "PMC11702489" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 glycosylation modulates its stability and activity.", "mechanism": "Increased BACE1 activity in platelets of AD and MCI patients enhances amyloidogenic APP processing and A\u03b2 generation.", "protein": "BACE1", "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "SELP is a heavily glycosylated adhesion molecule; glycosylation is essential for ligand binding.", "mechanism": "Platelet activation marker SELP is elevated in AD patients with faster cognitive decline.", "protein": "SELP (Selectin P)", "relationship_type": "biomarker", "source_pmcid": "PMC11702489" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Integrin glycosylation regulates receptor function and platelet aggregation.", "mechanism": "Increased expression in platelets correlates with cognitive decline and AD progression.", "protein": "ITGA2B/ITGB3 (Glycoprotein IIb/IIIa)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11702489" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GPIBA glycosylation is critical for ligand binding and platelet function.", "mechanism": "A\u03b2 activates platelets via GPIBA, promoting further platelet activation and vascular injury.", "protein": "GPIBA (Glycoprotein Ib alpha)", "protein_enriched": { "function": "GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium", "gene_name": "GP1BA", "glycan_count": 24, "glycosylation_sites_count": 44, "glytoucan_ids": [ "G49108TO", "G16150CJ", "G16774YZ", "G24432GW", "G38022PE", "G42686NQ", "G86750HK", "G96921ZU", "G01614ZM", "G11457RF", "G12396GB", "G46748BU", "G60890ZT", "G65562ZE", "G48414YA", "G52527GH", "G43417UB", "G56784JY", "G11629QQ", "G15169WU", "G22310AV", "G69834CE", "G74722FL", "G81006GJ" ], "uniprot_id": "P07359" }, "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD36 glycosylation affects receptor function and A\u03b2 binding.", "mechanism": "A\u03b2 activates platelets through CD36, leading to inflammation and oxidative stress.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "ADORA2A is glycosylated, influencing receptor signaling.", "mechanism": "Overexpression in platelets and hippocampus in AD; modulation may reduce neurodegeneration and platelet activation.", "protein": "ADORA2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11702489" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "SNCA glycosylation may affect aggregation and neurotoxicity.", "mechanism": "Activated platelets release SNCA, which is implicated in AD and Parkinson's disease pathogenesis.", "protein": "SNCA (Alpha-synuclein)", "relationship_type": "causal", "source_pmcid": "PMC11702489" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects laminin stability and ECM interactions.", "mechanism": "Serum laminin levels correlate with degree of liver fibrosis and cirrhosis.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates YKL-40 secretion and function.", "mechanism": "Elevated YKL-40 reflects macrophage activation and fibrosis progression.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may regulate IL-34 stability and receptor binding.", "mechanism": "Serum IL-34 levels correlate with baseline fibrosis scores in MASLD.", "protein": "IL-34", "protein_enriched": { "function": "Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate ", "gene_name": "IL34", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G80920RR" ], "uniprot_id": "Q6ZMJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences MMP-1 secretion and activity.", "mechanism": "Elevated MMP-1 reflects increased matrix degradation in MASLD.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates MMP-2 enzymatic activity.", "mechanism": "Elevated MMP-2 indicates active matrix remodeling in MASLD.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects TIMP-1 stability and inhibitory function.", "mechanism": "TIMP-1 inhibits MMPs, regulating matrix degradation in MASLD.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation is essential for collagen IV assembly and ECM integration.", "mechanism": "Serum collagen IV levels reflect ECM deposition and fibrosis.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "As a glycosaminoglycan, its structure is inherently glycan-based.", "mechanism": "Serum hyaluronic acid levels correlate with fibrosis severity.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Potential glycosylation may affect MFN2 localization and function.", "mechanism": "Reduced MFN2 expression leads to mitochondrial dysfunction and MASLD progression.", "protein": "MFN2", "protein_enriched": { "function": "Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dyn", "gene_name": "MFN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95140" }, "relationship_type": "causal", "source_pmcid": "PMC11703476" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "Glycosylation modulates YKL-40 tumor-promoting activity.", "mechanism": "Elevated YKL-40 in liver cancer patients suggests role in tumor progression.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC11703476" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation type 1A (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation reduces AT III function.", "mechanism": "Hypoglycosylation leads to decreased AT III activity, contributing to coagulation abnormalities.", "protein": "Antithrombin III (AT III)", "protein_enriched": { "function": "Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade (PubMed:15140129, PubMed:15853774). AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors I", "gene_name": "SERPINC1", "glycan_count": 111, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G10846ZT", "G11115RO", "G11911BT", "G14547CB", "G15169WU", "G20528HD", "G22310AV", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G30248BL", "G31986NC", "G34989PA", "G36442WJ", "G37412TK", "G37868ZX", "G37995HC", "G40574BA", "G40834TG", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G48414YA", "G53075ES", "G56518TU", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G63136LV", "G63980BQ", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G75983OB", "G78649WQ", "G78787DI", "G81124ET", "G82830MN", "G85554PZ", "G86182NS", "G86880BF", "G88374WZ", "G89045VA", "G92406TI", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G96091TT", "G99668VU", "G99801SM", "G01650EU", "G13694XX", "G16125XL", "G17208MA", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G28541PG", "G30970QQ", "G35253PZ", "G37399XV", "G39446WN", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G46450MZ", "G46691LC", "G46902YN", "G49642SA", "G49906RN", "G50045TK", "G54010QB", "G56014GC", "G61256FT", "G65092SV", "G70101JE", "G75418YA", "G76295SF", "G77669RF", "G82463GQ", "G84452RH", "G84862VB", "G85269DF", "G87661QW", "G90382BL", "G90659AW", "G93656SY", "G29068FM", "G43417UB", "G37881RL", "G49108TO" ], "uniprot_id": "P01008" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation type 1A (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation impairs Protein C secretion/function.", "mechanism": "Hypoglycosylation decreases Protein C activity, increasing thrombotic risk.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation type 1A (PMM2-CDG)", "glycan_involvement": "N-glycosylation defect reduces Protein S stability.", "mechanism": "Reduced glycosylation lowers Protein S levels, predisposing to thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "high", "disease": "Cerebral Hemorrhagic Infarction", "glycan_involvement": "N-glycosylation required for Factor XI secretion/function.", "mechanism": "Decreased Factor XI due to hypoglycosylation leads to bleeding tendency.", "protein": "Coagulation Factor XI", "protein_enriched": { "function": "Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX", "gene_name": "F11", "glycan_count": 43, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G13661YX", "G22310AV", "G31852PQ", "G37868ZX", "G40574BA", "G41247ZX", "G42358LZ", "G47518TP", "G48414YA", "G52527GH", "G56784JY", "G59626AS", "G62765YT", "G75983OB", "G80920RR", "G83460ZZ", "G93860XO", "G57888GL", "G10846ZT", "G11629QQ", "G37881RL", "G45395BF", "G70619PT", "G06247RL", "G08527WT", "G15169WU", "G22140GZ", "G23863VK", "G27947YN", "G41071NU", "G45495MK", "G47737VJ", "G50045TK", "G57818FI", "G58232MG", "G83646BJ", "G84452RH", "G90382BL" ], "uniprot_id": "P03951" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Venous Thrombosis", "glycan_involvement": "N-glycosylation affects prothrombin activity.", "mechanism": "Reduced glycosylation impairs prothrombin function, contributing to coagulation imbalance.", "protein": "Coagulation Factor II (Prothrombin)", "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "high", "disease": "Venous Thrombosis", "glycan_involvement": "Loss of glycoprotein sugars disrupts antithrombotic barrier.", "mechanism": "Glycocalyx disturbance from glycosylation defects leads to endothelial dysfunction and thrombosis.", "protein": "Endothelial Glycocalyx", "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "N-glycosylation required for Factor VII function.", "mechanism": "Reduced Factor VII due to hypoglycosylation contributes to DIC.", "protein": "Coagulation Factor VII", "protein_enriched": { "function": "Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or t", "gene_name": "F7", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G71142DF", "G84224TW", "G82576YO", "G96881BQ", "G06215XQ", "G08146BT", "G23695IQ", "G35061TJ", "G42358LZ", "G50739NP", "G71527NE", "G75494EI", "G91130VE", "G00912UN", "G08918WF", "G40574BA", "G43669FQ", "G45395BF" ], "uniprot_id": "P08709" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "N-glycosylation affects Factor X secretion/function.", "mechanism": "Hypoglycosylation reduces Factor X activity, promoting coagulopathy.", "protein": "Coagulation Factor X", "protein_enriched": { "function": "Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting (PubMed:22409427). Factor Xa activate", "gene_name": "F10", "glycan_count": 35, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G43417UB", "G53434XO", "G06356OH", "G18938DW", "G20425TQ", "G23863VK", "G24501HF", "G29857RC", "G32854GF", "G36191CD", "G41882MT", "G45359RY", "G46568MX", "G47012YE", "G49478NM", "G50045TK", "G59536GA", "G68866GS", "G72797UR", "G73073LQ", "G75850OP", "G78059CC", "G79809MM", "G81263BG", "G84452RH", "G85678WN", "G87123QX", "G88068QT", "G91365ZQ", "G00912UN", "G11314AS", "G57321FI", "G49108TO", "G80111QD", "G81006GJ" ], "uniprot_id": "P00742" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Cerebral Hemorrhagic Infarction", "glycan_involvement": "N-glycosylation required for Factor V stability.", "mechanism": "Reduced Factor V from glycosylation defect increases bleeding risk.", "protein": "Coagulation Factor V", "protein_enriched": { "function": "Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin", "gene_name": "F5", "glycan_count": 77, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G00031MO", "G10225UW", "G29931IJ", "G57321FI", "G74722FL", "G39558MO", "G43417UB", "G81006GJ", "G22140GZ", "G50045TK", "G72291OX", "G53434XO", "G63628AV", "G29068FM", "G27391WQ", "G58001LT", "G23294PN", "G82463GQ", "G84452RH", "G49108TO", "G00912UN", "G22310AV", "G35029YA", "G56784JY", "G62765YT", "G70418MS", "G78790NZ", "G91473PK", "G48414YA", "G57888GL", "G62461SM", "G04854VP", "G05933EN", "G06356OH", "G49644CL", "G31433PN", "G39595FH", "G35305EF", "G37881RL", "G55383ZG", "G81263BG", "G99966GV", "G08606CV", "G15169WU", "G23453IV", "G31916IQ", "G57776ZU", "G00033MO", "G32550BI", "G03382KH", "G06110VR", "G10256JP", "G25451PN", "G25637MV", "G29880MM", "G34730YF", "G51895WL", "G55220VL", "G82119TF", "G84820NF", "G98205FV", "G99858XP", "G47748JZ", "G59626AS", "G05724UK", "G39188ZX", "G72735IY", "G80966KZ", "G27993JQ", "G33791AF", "G34617SM", "G41882MT", "G50757KG", "G66760KM", "G72667IM", "G93656SY", "G08918WF" ], "uniprot_id": "P12259" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Cerebral Hemorrhagic Infarction", "glycan_involvement": "N-glycosylation required for Factor IX function.", "mechanism": "Decreased Factor IX due to glycosylation defect contributes to bleeding.", "protein": "Coagulation Factor IX", "protein_enriched": { "function": "Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipid", "gene_name": "F9", "glycan_count": 37, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27608TI", "G50236GJ", "G70593HA", "G76163CP", "G96881BQ", "G10651WD", "G45637XA", "G70649KP", "G81006GJ", "G29068FM", "G43417UB", "G18717LR", "G74722FL", "G57321FI", "G10008NR", "G12743GW", "G12793SR", "G15016TE", "G15169WU", "G17827EU", "G28847IN", "G31639NG", "G32551IQ", "G38277AO", "G39595FH", "G47518TP", "G48414YA", "G52527GH", "G58489ZK", "G66088HZ", "G69834CE", "G74815GQ", "G79318PG", "G86904UH", "G87108ET", "G92975MH", "G98725UL" ], "uniprot_id": "P00740" }, "relationship_type": "causal", "source_pmcid": "PMC11705677" }, { "confidence": "medium", "disease": "Amyloid pathology", "glycan_involvement": "APP glycosylation modulates amyloid-beta production and aggregation.", "mechanism": "Higher ALT and lower AST/ALT ratio associated with increased amyloid deposition over time.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11709349" }, { "confidence": "medium", "disease": "Tau pathology", "glycan_involvement": "Tau glycosylation affects aggregation and neurotoxicity.", "mechanism": "Lower total bilirubin associated with increased tau deposition.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11709349" }, { "confidence": "high", "disease": "Amyloid pathology", "glycan_involvement": "ALT is glycosylated; altered glycosylation may reflect liver dysfunction.", "mechanism": "Higher ALT predicts greater amyloid accumulation.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709349" }, { "confidence": "high", "disease": "Amyloid pathology", "glycan_involvement": "Glycosylation status may affect enzyme stability and function.", "mechanism": "Lower AST/ALT ratio predicts greater amyloid accumulation.", "protein": "AST to ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11709349" }, { "confidence": "medium", "disease": "Tau pathology", "glycan_involvement": "Bilirubin is conjugated with glucuronic acid (glycosylation) for excretion.", "mechanism": "Higher bilirubin levels are protective against tau accumulation.", "protein": "Bilirubin", "relationship_type": "protective", "source_pmcid": "PMC11709349" }, { "confidence": "low", "disease": "Amyloid pathology", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "AST alone not associated with amyloid or tau changes.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "none", "source_pmcid": "PMC11709349" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation regulates cleavage and amyloid-beta generation.", "mechanism": "Amyloid deposition is a hallmark of AD progression.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11709349" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau glycosylation influences aggregation and neurodegeneration.", "mechanism": "Tau deposition is a hallmark of AD progression.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11709349" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may reflect liver-brain axis dysfunction.", "mechanism": "Higher ALT linked to increased AD pathology.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11709349" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation (conjugation) affects bilirubin clearance and neuroprotection.", "mechanism": "Lower bilirubin linked to increased AD pathology.", "protein": "Bilirubin", "relationship_type": "protective", "source_pmcid": "PMC11709349" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GlycA measures N-acetyl groups on acute-phase glycoproteins; increased glycosylation correlates with inflammation.", "mechanism": "Elevated GlycA reflects peripheral inflammation associated with AD risk and progression.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "GlycA quantifies glycosylation changes in plasma proteins linked to inflammation.", "mechanism": "Higher baseline GlycA predicts future executive function decline in LMCI patients.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Reflects increased glycosylation of acute-phase proteins during inflammation.", "mechanism": "Elevated GlycA at baseline associates with progression from MCI to AD over 3 years.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of HDL apolipoproteins affects inflammatory and metabolic signaling.", "mechanism": "Altered glycoprotein composition of HDL correlates with AD status.", "protein": "Lipoproteins (HDL-associated glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Targeting glycosylation pathways may modulate inflammatory glycoprotein levels.", "mechanism": "Peripheral inflammation indicated by GlycA may be a target for intervention to reduce AD risk.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11709500" }, { "confidence": "medium", "disease": "Brain structural atrophy", "glycan_involvement": "Glycosylation changes in plasma proteins reflect systemic inflammation impacting neurodegeneration.", "mechanism": "Higher GlycA associates with future entorhinal cortex volume loss.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "medium", "disease": "MCI to AD conversion", "glycan_involvement": "Altered glycosylation patterns distinguish converters from non-converters.", "mechanism": "Distinct peripheral-central metabolic signatures in MCI-AD converters involve GlycA.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "low", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation modulates HDL function and inflammatory signaling.", "mechanism": "Specific HDL glycoprotein components correlate with cognitive status.", "protein": "Lipoproteins (HDL-associated glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC11709500" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of acute-phase proteins mediates inflammatory response.", "mechanism": "Peripheral inflammation may contribute to AD pathogenesis.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "causal", "source_pmcid": "PMC11709500" }, { "confidence": "low", "disease": "Cognitive decline", "glycan_involvement": "Reduced glycosylation of inflammatory proteins reflects lower systemic inflammation.", "mechanism": "Lower GlycA may indicate reduced risk of future cognitive decline.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "protective", "source_pmcid": "PMC11709500" }, { "confidence": "high", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Glycosylation is essential for p-gp trafficking and function at the BBB.", "mechanism": "Reduced efflux transport capacity in AD-derived brain endothelial cells, leading to impaired clearance of neurotoxic substrates.", "protein": "P-glycoprotein (p-gp)", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218, PubMed:35507548). Catalyzes the flop of phospholipids from the cytoplasmic to", "gene_name": "ABCB1", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G53677UQ", "G67961DI", "G80920RR" ], "uniprot_id": "P08183" }, "relationship_type": "causal", "source_pmcid": "PMC11709605" }, { "confidence": "high", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Glycosylation regulates BCRP stability and localization.", "mechanism": "Decreased BCRP-mediated efflux in AD-derived BECs, contributing to accumulation of toxic metabolites.", "protein": "Breast Cancer Resistant Protein (BCRP)", "protein_enriched": { "function": "Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cel", "gene_name": "ABCG2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UNQ0" }, "relationship_type": "causal", "source_pmcid": "PMC11709605" }, { "confidence": "high", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "N-glycosylation modulates MRP-1 activity at the BBB.", "mechanism": "Impaired MRP-1 function in AD-BECs reduces neuroprotective efflux of endogenous and exogenous compounds.", "protein": "Multidrug Resistant Protein 1 (MRP-1)", "protein_enriched": { "function": "Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and ", "gene_name": "ABCC1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P33527" }, "relationship_type": "causal", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Cerebral hypoperfusion", "glycan_involvement": "Shear stress may influence glycosylation and membrane localization of p-gp.", "mechanism": "Shear stress restores p-gp efflux function in BECs, suggesting vascular flow protects BBB transporter activity.", "protein": "P-glycoprotein (p-gp)", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218, PubMed:35507548). Catalyzes the flop of phospholipids from the cytoplasmic to", "gene_name": "ABCB1", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G53677UQ", "G67961DI", "G80920RR" ], "uniprot_id": "P08183" }, "relationship_type": "protective", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Cerebral hypoperfusion", "glycan_involvement": "Shear stress may affect glycan-dependent trafficking of BCRP.", "mechanism": "Shear stress reverses BCRP impairment in AD-BECs, maintaining efflux capacity.", "protein": "Breast Cancer Resistant Protein (BCRP)", "protein_enriched": { "function": "Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cel", "gene_name": "ABCG2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UNQ0" }, "relationship_type": "protective", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Cerebral hypoperfusion", "glycan_involvement": "Potential modulation of glycosylation under flow conditions.", "mechanism": "Shear stress normalizes MRP-1 function in AD-BECs, supporting BBB integrity.", "protein": "Multidrug Resistant Protein 1 (MRP-1)", "protein_enriched": { "function": "Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and ", "gene_name": "ABCC1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P33527" }, "relationship_type": "protective", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Altered glycosylation may underlie reduced transporter function.", "mechanism": "Reduced p-gp activity in AD-BECs may serve as a biomarker for BBB dysfunction in AD.", "protein": "P-glycoprotein (p-gp)", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218, PubMed:35507548). Catalyzes the flop of phospholipids from the cytoplasmic to", "gene_name": "ABCB1", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G53677UQ", "G67961DI", "G80920RR" ], "uniprot_id": "P08183" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Glycosylation status may reflect disease state.", "mechanism": "Decreased BCRP function in AD-BECs could indicate BBB impairment.", "protein": "Breast Cancer Resistant Protein (BCRP)", "protein_enriched": { "function": "Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cel", "gene_name": "ABCG2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UNQ0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Disease-associated glycan changes may impact MRP-1.", "mechanism": "MRP-1 dysfunction in AD-BECs may be a marker of altered BBB transport.", "protein": "Multidrug Resistant Protein 1 (MRP-1)", "protein_enriched": { "function": "Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and ", "gene_name": "ABCC1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P33527" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709605" }, { "confidence": "medium", "disease": "Alzheimer's disease (familial, PSEN2 N141I)", "glycan_involvement": "Targeting glycosylation could enhance p-gp activity.", "mechanism": "Restoring p-gp function may improve drug delivery and neuroprotection in AD.", "protein": "P-glycoprotein (p-gp)", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218, PubMed:35507548). Catalyzes the flop of phospholipids from the cytoplasmic to", "gene_name": "ABCB1", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G53677UQ", "G67961DI", "G80920RR" ], "uniprot_id": "P08183" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11709605" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "CHI3L1 is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "CHI3L1 is highly induced in AD and marks neuroinflammatory states.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation enables CHI3L1 secretion and receptor binding.", "mechanism": "Astrocyte-secreted CHI3L1 inhibits NSC proliferation/differentiation, enhances Ab production, tau phosphorylation, and neuronal apoptosis.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "causal", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for CHI3L1 function.", "mechanism": "CHI3L1 induction by pro-inflammatory stimuli (IL-1b, Ab42, AQP4 IgG) drives neurotoxic inflammation.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "causal", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Neuromyelitis optica (NMO)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "CHI3L1 is induced by AQP4 IgG autoantibody in NMO, marking astrocyte activation.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709996" }, { "confidence": "medium", "disease": "Neuromyelitis optica (NMO)", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "CHI3L1 mediates neuroinflammatory toxicity in NMO models.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "causal", "source_pmcid": "PMC11709996" }, { "confidence": "medium", "disease": "Aging (brain)", "glycan_involvement": "Glycosylation required for detection.", "mechanism": "CHI3L1 is elevated in aging brain, marking inflammation.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709996" }, { "confidence": "medium", "disease": "Trauma (brain)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "CHI3L1 is induced in brain trauma, marking neuroinflammatory response.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709996" }, { "confidence": "medium", "disease": "Autoimmune disorders (brain)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "CHI3L1 is elevated in autoimmune-mediated brain inflammation.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Targeting glycosylated CHI3L1 may modulate its activity.", "mechanism": "CHI3L1 depletion in astrocytes rescues neurogenesis and cognitive deficits in AD models.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may affect receptor interaction.", "mechanism": "Targeting CHI3L1/CRTH2/\u03b2-catenin pathway restores neurogenesis and cognitive function.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11709996" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Clusterin's glycosylation is essential for its structure and interaction with A\u03b2.", "mechanism": "Clusterin inhibits A\u03b2 fibrilization and oligomerization, reducing neurotoxicity.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC11710050" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Fragment glycosylation may affect binding and inhibitory function.", "mechanism": "Clusterin #2 fragment strongly inhibits A\u03b2 oligomerization and restores cell viability after A\u03b2 protofibril exposure.", "protein": "Clusterin fragment #2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11710050" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate fragment activity.", "mechanism": "Clusterin #3 fragment moderately inhibits A\u03b2 oligomerization and increases cell viability.", "protein": "Clusterin fragment #3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11710050" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may affect plasma stability and detection.", "mechanism": "Decreased plasma clusterin levels observed in AD patients compared to healthy controls.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC11710050" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of clusterin may influence complex formation.", "mechanism": "Reduced clusterin-A\u03b2 co-interaction in AD plasma samples indicates impaired A\u03b2 clearance.", "protein": "Clusterin-A\u03b2 complex", "relationship_type": "biomarker", "source_pmcid": "PMC11710050" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation is required for clusterin's chaperone activity.", "mechanism": "Impaired clusterin-mediated A\u03b2 clearance may contribute to AD pathology progression.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "causal", "source_pmcid": "PMC11710050" }, { "confidence": "high", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "N-glycosylation modulates APOE stability and receptor interactions.", "mechanism": "APOE variants (especially rs429358) increase risk for DLB via lipid metabolism and amyloid processing.", "protein": "APOE", "relationship_type": "causal", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation affects GBA folding and lysosomal targeting.", "mechanism": "GBA mutations impair lysosomal function, promoting alpha-synuclein aggregation.", "protein": "GBA", "protein_enriched": { "function": "Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-", "gene_name": "GBA1", "glycan_count": 36, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G08110WX", "G11870QZ", "G12313PD", "G25059MC", "G25451PN", "G30769VJ", "G34617SM", "G45495MK", "G46524LG", "G47448YK", "G55383ZG", "G62894KT", "G72291OX", "G74724QE", "G84452RH", "G90093AU", "G49108TO", "G08146BT", "G22310AV", "G39188ZX", "G64527OM", "G71146HJ", "G75983OB", "G80920RR", "G81198YO", "G86795LJ", "G01760ZU", "G05724UK", "G14260UH", "G22573RC", "G22768VO", "G48584BU", "G55037KS", "G65092SV", "G70101JE", "G11314AS" ], "uniprot_id": "P04062" }, "relationship_type": "causal", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Potential O-glycosylation may influence aggregation propensity.", "mechanism": "SNCA encodes alpha-synuclein, a major component of Lewy bodies.", "protein": "SNCA", "relationship_type": "causal", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation may affect membrane association.", "mechanism": "BIN1 variants modulate endocytosis and tau pathology.", "protein": "BIN1", "protein_enriched": { "function": "Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma memb", "gene_name": "BIN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00499" }, "relationship_type": "risk factor", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation may regulate channel localization.", "mechanism": "TMEM175 variants affect lysosomal potassium channel function.", "protein": "TMEM175", "protein_enriched": { "function": "Endoplasmic reticulum (ER)-anchored autophagy regulator which mediates ER delivery into lysosomes through sequestration into autophagosomes (PubMed:26040720, PubMed:31930741, PubMed:34338405). Promote", "gene_name": "RETREG1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H6L5" }, "relationship_type": "risk factor", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation modulates PLCG2 activity and membrane targeting.", "mechanism": "PLCG2 variants influence microglial signaling and neuroinflammation.", "protein": "PLCG2", "protein_enriched": { "function": "The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a cru", "gene_name": "PLCG2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P16885" }, "relationship_type": "risk factor", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell-cell interactions.", "mechanism": "CNTN1 involved in neuronal adhesion and synaptic stability.", "protein": "CNTN1", "relationship_type": "risk factor", "source_pmcid": "PMC11710463" }, { "confidence": "low", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Potential glycosylation may affect USP13 stability and function.", "mechanism": "USP13 regulates protein ubiquitination, contributing to Lewy body formation.", "protein": "USP13", "protein_enriched": { "function": "Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradatio", "gene_name": "USP13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92995" }, "relationship_type": "causal (suggestive)", "source_pmcid": "PMC11710463" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "PSGs are highly N-glycosylated; glycosylation may affect their immunomodulatory properties and neuroinflammation relevant to AD.", "mechanism": "A haplotype containing PSG gene cluster near rs10423769_A allele is associated with reduced AD risk in APOE4 carriers of African ancestry. Structural variation and differential methylation in this region may modulate PSG expression or function.", "protein": "Pregnancy-specific beta-1 glycoprotein (PSG)", "relationship_type": "protective", "source_pmcid": "PMC11710729" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates TREM2 cell surface expression and ligand binding.", "mechanism": "Genetic risk factor; regulates microglia activation and amyloid beta clearance.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC11710759" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD9 is a glycoprotein; glycosylation may affect its membrane localization and interaction with TREM2.", "mechanism": "CD9 interacts with TREM2 isoforms, possibly influencing cell adhesion and microglial migration.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "potential causal", "source_pmcid": "PMC11710759" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APOE glycosylation affects lipid binding and receptor interactions.", "mechanism": "APOE is a genetic risk factor; interacts with TREM2 and amyloid beta.", "protein": "APOE", "relationship_type": "causal", "source_pmcid": "PMC11710759" }, { "confidence": "medium", "disease": "Tauopathy", "glycan_involvement": "Tau O-glycosylation modulates aggregation propensity.", "mechanism": "Tau aggregation forms neurofibrillary tangles; interacts with TREM2.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC11710759" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation reported for CALM; interaction may affect glycoprotein signaling.", "mechanism": "CALM interacts with TREM2 isoforms, suggesting a role in calcium regulation linked to AD.", "protein": "CALM (Calmodulin)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P62158" }, "relationship_type": "potential causal", "source_pmcid": "PMC11710759" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "DAP12 glycosylation may regulate its stability and signaling.", "mechanism": "DAP12 mediates TREM2 signaling, affecting microglial response.", "protein": "DAP12", "protein_enriched": { "function": "Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the rec", "gene_name": "TYROBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43914" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11710759" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect TMEM59 membrane trafficking.", "mechanism": "TMEM59 interacts with TREM2, regulating protein degradation and possibly amyloid processing.", "protein": "TMEM59", "protein_enriched": { "function": "", "gene_name": "SPATC1L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0A9" }, "relationship_type": "potential causal", "source_pmcid": "PMC11710759" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation, Type Iaa", "glycan_involvement": "Defective N-linked glycosylation due to impaired dolichol carrier synthesis.", "mechanism": "NUS1 is essential for dolichol synthesis, which is required for N-linked glycosylation; loss-of-function leads to glycosylation defects.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "high", "disease": "Intellectual disability with seizures (autosomal dominant type 55)", "glycan_involvement": "Impaired N-linked glycosylation affects neuronal protein folding and function.", "mechanism": "NUS1 haploinsufficiency disrupts glycosylation and neuronal function, leading to intellectual disability and epilepsy.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "high", "disease": "Developmental and epileptic encephalopathy (DEE)", "glycan_involvement": "Disrupted N-linked glycosylation in neural development.", "mechanism": "De novo NUS1 variants cause glycosylation defects, resulting in developmental delay and epilepsy.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Defective glycosylation of neural proteins.", "mechanism": "NUS1 deletion impairs glycosylation, affecting neuronal excitability and seizure threshold.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "medium", "disease": "Tremor", "glycan_involvement": "Glycosylation pathway disruption affects motor neuron function.", "mechanism": "NUS1 deletion leads to lysosomal cholesterol accumulation and glycosylation defects, contributing to movement disorders.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "medium", "disease": "Ataxia", "glycan_involvement": "Impaired glycosylation in cerebellar neurons.", "mechanism": "NUS1 variants linked to ataxia via glycosylation and cholesterol metabolism defects.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "medium", "disease": "Kyphosis", "glycan_involvement": "Altered glycosylation of structural proteins.", "mechanism": "NUS1 deletion associated with musculoskeletal abnormalities, possibly via glycosylation defects affecting connective tissue proteins.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "medium", "disease": "Choreoathetosis/dyskinesias", "glycan_involvement": "Glycosylation defects in motor pathways.", "mechanism": "NUS1 deletion expands phenotype to include movement disorders, likely via glycosylation and cholesterol metabolism disruption.", "protein": "NUS1 (Nogo-B receptor, NgBR)", "protein_enriched": { "function": "Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "TMEM30A", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01650EU", "G04657PL", "G08918WF", "G13131HA", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G72065MN", "G57321FI", "G10486CT", "G31852PQ", "G37399XV", "G72790NZ", "G83633GK", "G95865ZB", "G49108TO" ], "uniprot_id": "Q9NV96" }, "relationship_type": "causal", "source_pmcid": "PMC11710847" }, { "confidence": "low", "disease": "Intellectual disability", "glycan_involvement": "ROS1 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "ROS1 deletion (with NUS1) associated with delayed speech and intellectual disability.", "protein": "ROS1", "protein_enriched": { "function": "Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous s", "gene_name": "ROS1", "glycan_count": 1, "glycosylation_sites_count": 30, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08922" }, "relationship_type": "possible causal", "source_pmcid": "PMC11710847" }, { "confidence": "low", "disease": "Infertility", "glycan_involvement": "Golgi glycoprotein involved in trafficking and glycosylation.", "mechanism": "GOPC deletion (with NUS1) may contribute to infertility via Golgi function disruption.", "protein": "GOPC", "protein_enriched": { "function": "Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating", "gene_name": "GOPC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HD26" }, "relationship_type": "possible causal", "source_pmcid": "PMC11710847" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Adiponectin upregulates BCAA catabolism via PPM1K and AMPK, improving insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11711082" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "TNF-\u03b1 suppresses BCAA transporter (Slc1a5) and catabolism, promoting inflammation and metabolic dysfunction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects cytokine secretion and activity.", "mechanism": "IL-6 expression is increased in inflamed adipose tissue with defective BCAA metabolism, exacerbating insulin resistance.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation regulates extracellular release.", "mechanism": "Elevated BCAAs promote HMGB1 secretion, driving M1 macrophage polarization and adipose inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates IRS1 stability and signaling.", "mechanism": "BCKAs impair insulin-induced IRS1 phosphorylation, blocking insulin signaling in muscle.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation essential for serum stability.", "mechanism": "BCAA supplementation promotes albumin synthesis via mTOR activation, improving nitrogen balance in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect nuclear localization and activity.", "mechanism": "PPAR\u03b3 activation upregulates BCAA catabolic genes, enhancing adipogenesis and insulin sensitivity.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation influences mitochondrial targeting.", "mechanism": "BCAA oxidation in BAT via UCP1 promotes thermogenesis and energy expenditure.", "protein": "UCP1", "protein_enriched": { "function": "Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and", "gene_name": "UCP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25874" }, "relationship_type": "protective", "source_pmcid": "PMC11711082" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may regulate nuclear function.", "mechanism": "Muscle-specific HDAC3 deletion increases BCAA catabolism, but also causes insulin resistance.", "protein": "HDAC3", "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "O-glycosylation (O-GlcNAc) directly modifies PDH activity.", "mechanism": "Elevated BCAAs induce O-GlcNAc modification of PDH, inhibiting glucose oxidation and promoting fibrosis.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC11711082" }, { "confidence": "high", "disease": "SLC10A7-CDG", "glycan_involvement": "Defective O-GalNAc glycosylation (loss of core 2, reduced core 1)", "mechanism": "Altered electrophoretic mobility due to O-GalNAc glycosylation defect in SLC10A7-deficient cells", "protein": "TGN46", "protein_enriched": { "function": "Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation. May play a role as a scaffolding protein to recruit Rho-GDP and Rho-GEF, thereby enhancing Rho-GTP formation. Can", "gene_name": "DAAM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4D1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "SLC10A7-CDG", "glycan_involvement": "Defective N- and O-GalNAc glycosylation", "mechanism": "Altered gel mobility indicating N- and O-GalNAc glycosylation defects in patient fibroblasts", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "biomarker", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "SLC10A7-CDG", "glycan_involvement": "Impaired core 1 O-GalNAc glycosylation", "mechanism": "Reduced protein levels in most SLC10A7-CDG patients, impairing core 1 O-glycan synthesis", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "SLC10A7-CDG", "glycan_involvement": "Defective extension of O-GalNAc glycans (Tn antigen exposure)", "mechanism": "Altered COSMC levels disrupt C1GALT1 folding and function, leading to Tn antigen accumulation", "protein": "COSMC", "protein_enriched": { "function": "Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain ", "gene_name": "ERO1A", "glycan_count": 25, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G11314AS", "G15664MX", "G20579QQ", "G25079LO", "G28681TP", "G31852PQ", "G35029YA", "G39188ZX", "G41247ZX", "G46503DX", "G57317CE", "G62765YT", "G63040RU", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "Q96HE7" }, "relationship_type": "causal", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "SLC10A7-CDG", "glycan_involvement": "Indirect; Cab45 is a sensor for Golgi Ca2+ homeostasis affecting glycosylation", "mechanism": "Loss of Golgi localization and secretion of Cab45 in SLC10A7-deficient cells due to Ca2+ homeostasis disruption", "protein": "Cab45", "protein_enriched": { "function": "May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment", "gene_name": "SDF4", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q9BRK5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "Tn syndrome", "glycan_involvement": "Accumulation of Tn antigen (GalNAc\u03b11-O-Ser/Thr)", "mechanism": "COSMC deficiency leads to C1GALT1 malfunction and Tn antigen exposure", "protein": "COSMC", "protein_enriched": { "function": "Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain ", "gene_name": "ERO1A", "glycan_count": 25, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G11314AS", "G15664MX", "G20579QQ", "G25079LO", "G28681TP", "G31852PQ", "G35029YA", "G39188ZX", "G41247ZX", "G46503DX", "G57317CE", "G62765YT", "G63040RU", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "Q96HE7" }, "relationship_type": "causal", "source_pmcid": "PMC11711720" }, { "confidence": "medium", "disease": "Cancer (aggressiveness/metastasis)", "glycan_involvement": "Presence of unextended O-GalNAc (Tn antigen)", "mechanism": "High Tn antigen levels correlate with poor prognosis and metastasis", "protein": "Tn antigen (on various proteins)", "relationship_type": "biomarker", "source_pmcid": "PMC11711720" }, { "confidence": "medium", "disease": "Cancer (aggressiveness/metastasis)", "glycan_involvement": "Extension of O-GalNAc glycans beyond Tn antigen", "mechanism": "Proper C1GALT1 function prevents Tn antigen accumulation, reducing cancer aggressiveness", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "protective", "source_pmcid": "PMC11711720" }, { "confidence": "medium", "disease": "SLC10A7-CDG", "glycan_involvement": "Increased transfer of GalNAc residues, defective glycan elongation", "mechanism": "Altered Ca2+/Mn2+ homeostasis affects ppGalNAc-Ts activity, increasing GalNAc transfer and impairing glycan extension", "protein": "ppGalNAc-Ts", "relationship_type": "causal", "source_pmcid": "PMC11711720" }, { "confidence": "medium", "disease": "Golgi Ca2+ homeostasis disorders", "glycan_involvement": "Indirect; marker for glycosylation impairment due to Ca2+ imbalance", "mechanism": "Cab45 secretion indicates Golgi Ca2+ dysregulation, which impacts glycosylation", "protein": "Cab45", "protein_enriched": { "function": "May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment", "gene_name": "SDF4", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q9BRK5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11711720" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GPR39 is a glycosylated GPCR; glycosylation may affect receptor trafficking, stability, and ligand binding.", "mechanism": "Dysregulation of GPR39 alters Zn2+ homeostasis, leading to oxidative stress, neuroinflammation, microtubule destabilization, synaptic dysfunction, and tau phosphorylation.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712597" }, { "confidence": "medium", "disease": "Alzheimer's disease-related dementia (ADRD)", "glycan_involvement": "Glycosylation of GPR39 may modulate its function and cell surface expression.", "mechanism": "GPR39 dysregulation contributes to Zn2+ dyshomeostasis and neurodegenerative processes in ADRD.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712597" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status may influence PET tracer binding and receptor accessibility.", "mechanism": "Reduced brain uptake of GPR39-targeted PET tracer in AD mouse models indicates altered GPR39 expression/activity.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712597" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "PGRN is a glycoprotein; glycosylation is essential for its secretion and stability.", "mechanism": "Reduced PGRN levels due to GRN gene variants increase AD risk by impairing lysosomal function and neuroinflammation regulation.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "causal", "source_pmcid": "PMC11712613" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects PGRN detection and quantification in biofluids.", "mechanism": "Lower plasma and CSF PGRN levels are associated with increased AD risk.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712613" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "SORT1 is a glycoprotein; glycosylation may affect receptor-ligand interactions.", "mechanism": "SORT1 mediates PGRN degradation; inhibition increases extracellular PGRN, potentially ameliorating AD pathology.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712613" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Therapeutic IgG1 glycosylation affects antibody stability and effector function.", "mechanism": "GSK4527226 inhibits SORT1, elevating PGRN levels in plasma and CSF.", "protein": "Immunoglobulin G1 (GSK4527226/AL101)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC11712613" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "Glycosylation impacts PGRN stability and bioavailability.", "mechanism": "PGRN levels may reflect disease progression in early AD continuum.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712613" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "Glycosylation may modulate SORT1 function.", "mechanism": "SORT1 inhibition may increase PGRN and slow progression to AD.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712613" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for PGRN secretion and function.", "mechanism": "Elevated PGRN has neurotrophic and anti-inflammatory effects, potentially protecting against AD.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "protective", "source_pmcid": "PMC11712613" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence SORT1 trafficking and activity.", "mechanism": "SORT1-mediated degradation of PGRN contributes to reduced neuroprotection in AD.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. 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"G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712666" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "TfR glycosylation may modulate antibody binding and transport efficiency.", "mechanism": "cTfRMAb enables EPO to cross the BBB, targeting AD pathology.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11712666" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "ALT is glycosylated, affecting its stability and serum half-life.", "mechanism": "ALT levels monitored to assess hepatic safety in AD patients treated with IGC-AD1.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "AST glycosylation influences its secretion and activity.", "mechanism": "AST levels used to monitor liver function in AD patients under IGC-AD1 treatment.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "ALP is highly glycosylated, which modulates its enzymatic activity.", "mechanism": "ALP changes reflect hepatic response to IGC-AD1 dosing in AD patients.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Hepatic Complications", "glycan_involvement": "Glycosylation affects ALT's serum stability and detection.", "mechanism": "ALT elevation indicates potential liver injury in AD patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Hepatic Complications", "glycan_involvement": "Glycosylation modulates AST's activity and clearance.", "mechanism": "AST elevation signals hepatic stress in AD patients.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Hepatic Complications", "glycan_involvement": "ALP glycosylation affects its tissue specificity and function.", "mechanism": "ALP increase may indicate cholestatic liver injury in AD patients.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "medium", "disease": "Hepatic Complications", "glycan_involvement": "Indirect bilirubin is transported by glycoproteins (e.g., albumin).", "mechanism": "Indirect bilirubin levels reflect hepatic processing in AD patients.", "protein": "Indirect Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Stable glycosylation maintains ALT function.", "mechanism": "No significant ALT elevation with IGC-AD1 suggests hepatic safety in AD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11712695" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation ensures ALP stability.", "mechanism": "ALP levels remained within expected range, supporting safety of IGC-AD1.", "protein": "ALP", "relationship_type": "protective", "source_pmcid": "PMC11712695" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Transported by glycoproteins; glycosylation affects binding.", "mechanism": "Indirect bilirubin monitored for hepatic safety in AD patients.", "protein": "Indirect Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC11712695" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Trem2 is N-glycosylated, which is essential for its cell surface expression and function.", "mechanism": "Upregulated in disease-associated microglia (DAM); promotes microglial activation and phagocytosis of amyloid-beta.", "protein": "Trem2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11712709" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "DAP12 is N-glycosylated, affecting stability and signaling.", "mechanism": "Upregulated in DAM; forms a signaling complex with Trem2 to regulate microglial activation.", "protein": "Tyrobp (DAP12)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11712709" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD11c is N-glycosylated, modulating ligand binding and cell adhesion.", "mechanism": "Upregulated in DAM; marker of activated microglia involved in phagocytosis.", "protein": "Itgax (CD11c)", "protein_enriched": { "function": "Integrin alpha-X/beta-2 is a receptor for fibrinogen. It recognizes the sequence G-P-R in fibrinogen. It mediates cell-cell interaction during inflammatory responses. It is especially important in mon", "gene_name": "ITGAX", "glycan_count": 28, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G59626AS", "G07617FP", "G09724ZC", "G23799GS", "G81315DD", "G85238RP", "G92805XC", "G10756ZZ", "G22573RC", "G70101JE", "G80920RR", "G10486CT", "G10819WX", "G22768VO", "G27947YN", "G40926MX", "G42227JK", "G44753VC", "G59536GA", "G60033FS", "G99668VU", "G34442SS", "G94626GC", "G02815KT", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT" ], "uniprot_id": "P20702" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712709" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Clec7a is N-glycosylated, influencing ligand recognition.", "mechanism": "Upregulated in DAM; involved in recognition and clearance of pathogens and debris.", "protein": "Clec7a (Dectin-1)", "protein_enriched": { "function": "Lectin that functions as a pattern recognizing receptor (PRR) specific for beta-1,3-linked and beta-1,6-linked glucans, which constitute cell wall constituents from pathogenic bacteria and fungi (PubM", "gene_name": "CLEC7A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G53434XO", "G49108TO" ], "uniprot_id": "Q9BXN2" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712709" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD68 is heavily glycosylated, affecting lysosomal targeting.", "mechanism": "Upregulated in DAM; marker of phagocytic microglia.", "protein": "Cd68", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05316" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712709" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Lyz2 is glycosylated, influencing secretion and stability.", "mechanism": "Upregulated in DAM; involved in degradation of phagocytosed material.", "protein": "Lyz2", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents", "gene_name": "LYZ", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61626" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712709" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Cst7 is glycosylated, affecting secretion.", "mechanism": "Upregulated in DAM; regulates protease activity in microglia.", "protein": "Cst7", "protein_enriched": { "function": "High affinity inhibitor for cathepsin L, cathepsin L2 (cathepsin V), and legumain (PubMed:30425301). Involved in the regulation of epidermal cornification, and hair follicle morphogenesis and maintena", "gene_name": "CST6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15828" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712709" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GPR3 may be glycosylated at the N-terminus (HA tag used for detection), but specific glycan function not detailed.", "mechanism": "Biased GPR3 signaling in microglia enhances DAM profile, increases A\u03b2 plaque compaction, and reduces plaque area.", "protein": "GPR3", "protein_enriched": { "function": "Constitutively active G-protein coupled receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that a plays a role in serveral processes including meiotic arrest in oocytes or", "gene_name": "GPR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P46089" }, "relationship_type": "protective", "source_pmcid": "PMC11712709" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates secretion and stability.", "mechanism": "Upregulated in CSF; associated with neuroinflammation.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "high", "disease": "Frontotemporal dementia", "glycan_involvement": "N-glycosylation affects immune signaling.", "mechanism": "Upregulated in CSF; linked to glial activation.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "N-glycosylation influences protease inhibition.", "mechanism": "Upregulated in CSF; involved in complement activation.", "protein": "SERPINA3", "protein_enriched": { "function": "Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2", "gene_name": "SERPINA3", "glycan_count": 192, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05724UK", "G06110VR", "G06247RL", "G08146BT", "G08918WF", "G11115RO", "G11629QQ", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G27947YN", "G31665QC", "G34617SM", "G39188ZX", "G39595FH", "G42358LZ", "G43669FQ", "G45495MK", "G47518TP", "G48414YA", "G49739MP", "G52527GH", "G52890YB", "G53075ES", "G59626AS", "G60033FS", "G64527OM", "G66088HZ", "G69834CE", "G70232NH", "G71146HJ", "G71560PC", "G74728JK", "G75983OB", "G77582RK", "G81637OR", "G84452RH", "G86795LJ", "G89205CJ", "G93656SY", "G93860XO", "G94917XT", "G95678HJ", "G99679NM", "G49108TO", "G00273SJ", "G04854VP", "G05962QB", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G20706XG", "G23010ZW", "G23863VK", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G28681TP", "G29545VG", "G30740WO", "G31028YV", "G31986NC", "G33791AF", "G36442WJ", "G37412TK", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41882MT", "G42962KI", "G43223CG", "G44215PV", "G44753VC", "G45395BF", "G46450MZ", "G46503DX", "G46691LC", "G46902YN", "G47737VJ", "G49018RC", "G50856PC", "G51413EV", "G54010QB", "G56518TU", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59324HL", "G59536GA", "G60834IK", "G63980BQ", "G64394MX", "G66282NU", "G68490OW", "G69521XL", "G70619PT", "G70888PK", "G71463BG", "G72747WU", "G72797UR", "G72951AH", "G75418YA", "G75568BH", "G77459ND", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81263BG", "G82443XX", "G82830MN", "G83229XP", "G84467IZ", "G85269DF", "G86182NS", "G86880BF", "G89877QI", "G90386IR", "G92081HT", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G70418MS", "G88374WZ", "G07810QS", "G09700PF", "G09831WQ", "G10039CR", "G10488MI", "G11101UV", "G22572EH", "G29580WD", "G30221QT", "G31309XD", "G31852PQ", "G41044JW", "G43734MM", "G44211QA", "G45526EA", "G46665ZP", "G49755GI", "G50427EO", "G52848YE", "G56770VP", "G63040RU", "G64751KD", "G65344XH", "G66537LK", "G72309KR", "G74381CZ", "G78790NZ", "G81124ET", "G83213GG", "G84225JN", "G85144OK", "G87399DK", "G90789YQ", "G92275SC", "G92551JA", "G96577RX", "G57321FI", "G29068FM", "G43417UB", "G28622IK", "G33416PL", "G37692EO", "G39471UU", "G61256FT", "G63136LV", "G85282JO", "G85554PZ", "G94310CV", "G98129XB" ], "uniprot_id": "P01011" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates cell signaling.", "mechanism": "Differentially expressed; may regulate extracellular matrix.", "protein": "SMOC1", "protein_enriched": { "function": "Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation", "gene_name": "SMOC1", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT", "G57321FI", "G43417UB", "G53434XO", "G00912UN", "G02815KT", "G27058EU", "G61256FT", "G76295SF" ], "uniprot_id": "Q9H4F8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies", "glycan_involvement": "N-glycosylation affects synaptic localization.", "mechanism": "Downregulated; involved in synaptic function.", "protein": "NPTX2", "protein_enriched": { "function": "May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses", "gene_name": "NPTX1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q15818" }, "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies", "glycan_involvement": "O-glycosylation may regulate peptide processing.", "mechanism": "Downregulated; neuropeptide involved in synaptic plasticity.", "protein": "VGF", "relationship_type": "biomarker", "source_pmcid": "PMC11712855" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "GPR3 is a glycosylated GPCR; glycosylation may affect receptor trafficking and function.", "mechanism": "GPR3 signaling in astrocytes modulates A\u03b2 plaque burden and neuroinflammation.", "protein": "GPR3", "protein_enriched": { "function": "Constitutively active G-protein coupled receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that a plays a role in serveral processes including meiotic arrest in oocytes or", "gene_name": "GPR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P46089" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713493" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may influence filament assembly.", "mechanism": "Astrocyte activation and hypertrophy marked by increased GFAP expression in AD pathology.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "Upregulated in Biased AD KI mice, contributing to inflammatory response.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-5 glycosylation regulates stability and receptor interaction.", "mechanism": "Differentially expressed in astrocytes, modulating immune response.", "protein": "IL-5", "protein_enriched": { "function": "Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:2653458, PubMed:9010276)", "gene_name": "IL5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P05113" }, "relationship_type": "causal", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for lectin activity.", "mechanism": "Lectin family proteins upregulated in activated astrocytes, indicating inflammation.", "protein": "Chil3/5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates chemokine gradient formation.", "mechanism": "Chemokine involved in immune cell recruitment in AD brain.", "protein": "Ccl6", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "Ndufa7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1P6" }, "relationship_type": "causal", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects chemokine-receptor binding.", "mechanism": "Chemokine upregulated in astrocytes, promoting neuroinflammatory signaling.", "protein": "Ccl9", "protein_enriched": { "function": "May be involved in the control of cytoskeleton formation by regulating actin polymerization", "gene_name": "Kank3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1P7" }, "relationship_type": "causal", "source_pmcid": "PMC11713493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation influences chemokine stability.", "mechanism": "Chemokine mediates immune cell migration in AD pathology.", "protein": "Cxcl9", "protein_enriched": { "function": "Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released (PubMed:19812333). After synthesis, participates in the for", "gene_name": "Pclo", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q9QYX7" }, "relationship_type": "causal", "source_pmcid": "PMC11713493" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Growth factor differentially expressed, may support neuroprotection.", "protein": "Fgf3", "protein_enriched": { "function": "Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal ear development", "gene_name": "FGF3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P11487" }, "relationship_type": "protective", "source_pmcid": "PMC11713493" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates receptor interaction.", "mechanism": "Growth factor involved in vascular and neuronal support.", "protein": "Pdgfd", "protein_enriched": { "function": "Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory", "gene_name": "Thbs4", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G73968GN" ], "uniprot_id": "Q9Z1T2" }, "relationship_type": "protective", "source_pmcid": "PMC11713493" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation of vitronectin may affect its aggregation and deposition in amyloid plaques.", "mechanism": "Vitronectin is found in abnormal amyloid deposits associated with AD pathology.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713586" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment", "glycan_involvement": "Altered glycosylation may modulate vitronectin's role in neurodegeneration.", "mechanism": "Plasma vitronectin levels distinguish MCI subgroups and predict progression.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713586" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "APOE is N-glycosylated, which may influence its lipid transport and amyloid interaction.", "mechanism": "APOE\u03b54 allele status is a strong risk factor for AD; protein is part of plasma signature.", "protein": "APOE (Apolipoprotein E)", "relationship_type": "biomarker", "source_pmcid": "PMC11713586" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its trafficking and processing.", "mechanism": "APP processing generates amyloid-\u03b2 (A\u03b2), which accumulates in AD pathology.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11713600" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GPR3 glycosylation may affect receptor trafficking and function.", "mechanism": "GPR3 signaling promotes A\u03b2 generation via interaction with APP.", "protein": "GPR3", "protein_enriched": { "function": "Constitutively active G-protein coupled receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that a plays a role in serveral processes including meiotic arrest in oocytes or", "gene_name": "GPR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P46089" }, "relationship_type": "causal", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GRK2 is glycosylated; glycosylation may regulate its localization and activity.", "mechanism": "GRK2 activity promotes A\u03b2 generation by modulating GPR3 signaling and APP trafficking.", "protein": "GRK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Potential glycosylation may affect \u03b2-arrestin 2 interactions.", "mechanism": "\u03b2-arrestin 2 recruitment to GPR3 increases A\u03b2 generation.", "protein": "\u03b2-arrestin 2", "protein_enriched": { "function": "Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-a", "gene_name": "ARRB2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P32121" }, "relationship_type": "causal", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Familial Alzheimer's disease", "glycan_involvement": "Glycosylation status may differ in mutant APP, affecting processing.", "mechanism": "Mutant APP in familial AD neurons leads to increased A\u03b2 generation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Familial Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate GRK2 function in neurons.", "mechanism": "Pharmacological inhibition of GRK2 reduces A\u03b2 generation in familial AD neurons.", "protein": "GRK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence APP phosphorylation and processing.", "mechanism": "Phosphorylation of APP at Thr668 increases upon GRK2 inhibition, potentially altering A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect biased signaling and receptor trafficking.", "mechanism": "G protein-biased GPR3 signaling reduces A\u03b2 generation and pathology.", "protein": "GPR3", "protein_enriched": { "function": "Constitutively active G-protein coupled receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that a plays a role in serveral processes including meiotic arrest in oocytes or", "gene_name": "GPR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P46089" }, "relationship_type": "protective", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of GRK2 may regulate its subcellular localization.", "mechanism": "GRK2 modulates localization of GPR3 and APP to Golgi, endosomes, and ER, affecting A\u03b2 generation.", "protein": "GRK2", "relationship_type": "causal", "source_pmcid": "PMC11713600" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation could be targeted to modulate GPR3 function.", "mechanism": "Targeting GPR3 signaling may reduce A\u03b2 pathology without adverse cognitive effects.", "protein": "GPR3", "protein_enriched": { "function": "Constitutively active G-protein coupled receptor that maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that a plays a role in serveral processes including meiotic arrest in oocytes or", "gene_name": "GPR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P46089" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713600" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 overexpression increases tau phosphorylation at AD-associated sites, promoting tau pathology.", "protein": "GRK2", "relationship_type": "causal", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 levels positively correlate with soluble tau and neurofibrillary tangle burden in AD brains.", "protein": "GRK2", "relationship_type": "biomarker", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "Pharmacological inhibition of GRK2 reduces pTau levels and oxidative stress in AD patient-derived neurons.", "protein": "GRK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "Impaired inactivation of GRK2 (decreased GRK2-S670) leads to increased pTau burden in AD.", "protein": "GRK2", "relationship_type": "causal", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "ERK-mediated inactivation of GRK2 (S670D) protects against elevated pTau levels.", "protein": "GRK2 (inactive, S670D mutant)", "relationship_type": "protective", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 directly interacts with tau and pTau, with enhanced interaction in AD patient-derived neurons.", "protein": "GRK2", "relationship_type": "causal", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 inhibition increases ERK activation and GRK2-S670 levels, reducing tau phosphorylation.", "protein": "GRK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 inhibition reduces oxidative stress in AD neurons, suggesting neuroprotective effects.", "protein": "GRK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713836" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "GRK2 implicated in phosphorylation of non-GPCR substrates (e.g., \u03b1-synuclein) in Parkinson's Disease (background context).", "protein": "GRK2", "relationship_type": "causal", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified in article.", "mechanism": "Hyperphosphorylated tau aggregates in neurofibrillary tangles, a hallmark of AD.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation is essential for its synaptic vesicle localization and function.", "mechanism": "Reduced SV2A PET binding reflects synaptic loss in AD brains.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC11714047" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is known to be O-glycosylated, which may affect aggregation and toxicity (not directly discussed in this article).", "mechanism": "Tau accumulation in epicenters is associated with synaptic loss in functionally connected regions.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11714047" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Glycosylation of SV2A is required for its stability and synaptic function.", "mechanism": "Lower SV2A PET binding observed in A\u00df+ MCI subjects, indicating early synaptic loss.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC11714047" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "O-glycosylation of tau may modulate its aggregation propensity.", "mechanism": "Early tau accumulation may drive synaptic loss in MCI, especially in regions connected to tau epicenters.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11714047" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status may influence SV2A PET ligand binding.", "mechanism": "SV2A PET imaging can be used to monitor synaptic integrity and potentially evaluate therapeutic efficacy.", "protein": "SV2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11714047" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may alter tau PET ligand binding and aggregation.", "mechanism": "Tau PET imaging identifies epicenters of pathology that predict downstream synaptic loss.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11714047" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "None (GFAP is not glycosylated)", "mechanism": "Elevated plasma GFAP reflects astrocytic activation and neurodegeneration.", "protein": "Glial fibrillary acidic protein", "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "None", "mechanism": "Increased GFAP indicates astrocyte reactivity and demyelination.", "protein": "Glial fibrillary acidic protein", "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation critical for secretion and stability; altered glycosylation may affect function.", "mechanism": "Elevated CHI3L1 in plasma marks glial activation and neuroinflammation.", "protein": "Chitinase-3-like protein 1", "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation modulates immune signaling and stability.", "mechanism": "High CHI3L1 levels reflect ongoing inflammation and demyelination.", "protein": "Chitinase-3-like protein 1", "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects chemokine gradient formation and receptor binding.", "mechanism": "CXCL13 elevation indicates B-cell recruitment and neuroinflammation.", "protein": "Chemokine (C-X-C motif) ligand 13", "protein_enriched": { "function": "Chemotactic for B-lymphocytes but not for T-lymphocytes, monocytes and neutrophils. Does not induce calcium release in B-lymphocytes. Binds to BLR1/CXCR5", "gene_name": "CXCL13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43927" }, "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "CXCL13 is a marker of CNS inflammation and B-cell activity.", "protein": "Chemokine (C-X-C motif) ligand 13", "protein_enriched": { "function": "Chemotactic for B-lymphocytes but not for T-lymphocytes, monocytes and neutrophils. Does not induce calcium release in B-lymphocytes. Binds to BLR1/CXCR5", "gene_name": "CXCL13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43927" }, "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "None (not glycosylated)", "mechanism": "Elevated Nfl in plasma reflects axonal injury and neurodegeneration.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "None", "mechanism": "High Nfl levels indicate ongoing axonal damage.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation required for plasma stability and detection.", "mechanism": "Early elevation (5-10 years pre-diagnosis) predicts conversion to AD.", "protein": "Chitinase-3-like protein 1", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation influences biomarker reliability.", "mechanism": "Early elevation predicts disease progression.", "protein": "Chitinase-3-like protein 1", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC11714931" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for secretion and stability; altered glycosylation may modulate inflammatory activity.", "mechanism": "Elevated in plasma of TSPO+ AD patients; reflects neuroinflammation and correlates with amyloid, tau, and TSPO PET uptake.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715190" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects secretion and protease inhibition; altered glycosylation may impact amyloid aggregation.", "mechanism": "Increased plasma levels in TSPO+ AD; associated with neuroinflammatory processes and amyloid/tau pathology.", "protein": "CST3 (Cystatin C)", "protein_enriched": { "function": "As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity", "gene_name": "CST3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01034" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715190" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for enzymatic activity and secretion.", "mechanism": "Elevated in plasma of TSPO+ AD; marker of microglial activation and neuroinflammation.", "protein": "CHIT1 (Chitotriosidase-1)", "protein_enriched": { "function": "Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity", "gene_name": "CHIT1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "Q13231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715190" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Increased in plasma of TSPO+ AD; reflects astrocyte activation and neuroinflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715190" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated in plasma of TSPO+ AD; associated with neuronal injury.", "protein": "FABP3", "relationship_type": "biomarker", "source_pmcid": "PMC11715190" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "O-mannosylation (core M3/matriglycan) required for function.", "mechanism": "Loss of O-mannosylation on \u03b1-DG impairs ECM binding, destabilizing sarcolemma.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy (LGMD R11 POMT1-related)", "glycan_involvement": "Initiates O-mannosylation of \u03b1-DG.", "mechanism": "POMT1 mutations prevent O-mannosylation of \u03b1-DG, leading to muscle weakness.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Walker Warburg Syndrome (WWS)", "glycan_involvement": "O-mannosylation of \u03b1-DG is lost.", "mechanism": "POMT1 deficiency disrupts \u03b1-DG glycosylation, causing brain, eye, and muscle defects.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Elongates matriglycan on core M3 O-mannosylation.", "mechanism": "LARGE1 loss prevents matriglycan synthesis on \u03b1-DG, impairing ECM binding.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Skeletal muscle myopathy", "glycan_involvement": "O-mannosylation (core M3/matriglycan) is essential.", "mechanism": "Absence of O-mannosylation/matriglycan leads to sarcolemma fragility and muscle degeneration.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Skeletal muscle myopathy", "glycan_involvement": "Restores O-mannosylation and matriglycan.", "mechanism": "Gene transfer of POMT1 restores \u03b1-DG glycosylation, improving muscle pathology.", "protein": "POMT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Skeletal muscle myopathy", "glycan_involvement": "Loss of matriglycan cap on core M3 O-mannosylation.", "mechanism": "LARGE1 deletion causes loss of matriglycan, leading to muscle weakness and sarcolemma instability.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Absence of O-mannosylation/matriglycan.", "mechanism": "Loss of matriglycan on \u03b1-DG is diagnostic for dystroglycanopathies.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "biomarker", "source_pmcid": "PMC11715199" }, { "confidence": "medium", "disease": "Neuromuscular dysfunction", "glycan_involvement": "O-mannosylation required for post-synaptic structure.", "mechanism": "Defective O-mannosylation impairs neuromuscular junction morphology and function.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "medium", "disease": "Muscle fiber remodeling defects", "glycan_involvement": "O-mannosylation/matriglycan required for normal remodeling.", "mechanism": "Loss of O-mannosylation leads to impaired muscle regeneration and increased central nuclei.", "protein": "Dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11715199" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GPR39 is a glycoprotein; glycosylation may affect receptor trafficking and function, influencing disease progression.", "mechanism": "Dysregulation of GPR39 disrupts zinc homeostasis, leading to oxidative stress, neuroinflammation, microtubule destabilization, synaptic dysfunction, and tau phosphorylation.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "causal", "source_pmcid": "PMC11715704" }, { "confidence": "high", "disease": "Alzheimer's disease and related dementia (ADRD)", "glycan_involvement": "Glycosylation status may affect PET tracer binding and receptor localization.", "mechanism": "GPR39 expression and distribution can be imaged to monitor zinc dyshomeostasis and neurodegeneration.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715704" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate receptor responsiveness to agonists.", "mechanism": "Pharmacologic modulation of GPR39 may restore zinc homeostasis and mitigate neurodegenerative processes.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11715704" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation affects its processing and A\u03b2 generation.", "mechanism": "Overexpression of APP leads to A\u03b2 accumulation, a hallmark of AD pathology.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11715704" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence PSEN1 stability and function.", "mechanism": "Mutations in PSEN1 alter \u03b3-secretase activity, increasing A\u03b2 production.", "protein": "PSEN1", "relationship_type": "causal", "source_pmcid": "PMC11715704" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect receptor availability for imaging.", "mechanism": "Reduced GPR39 PET tracer uptake in AD mouse models indicates altered receptor expression or function.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715704" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate receptor signaling pathways.", "mechanism": "GPR39 dysregulation triggers tau phosphorylation, contributing to neurofibrillary pathology.", "protein": "GPR39", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t", "gene_name": "CDH23", "glycan_count": 4, "glycosylation_sites_count": 41, "glytoucan_ids": [ "G08293MJ", "G84452RH", "G49108TO", "G80920RR" ], "uniprot_id": "Q9H251" }, "relationship_type": "causal", "source_pmcid": "PMC11715704" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect synaptic vesicle trafficking and stability.", "mechanism": "Reduced SV2A PET signal indicates synaptic density loss in WMH-connected cortex, correlating with AD pathology.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is glycosylated; glycosylation affects processing and aggregation of A\u03b2.", "mechanism": "Higher A\u03b2 deposition in WMH-connected cortex is associated with cortical thinning and cognitive decline.", "protein": "Beta-amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau glycosylation modulates aggregation and neurotoxicity.", "mechanism": "Increased tau deposition in WMH-connected cortex correlates with regional cortical degeneration.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "SV2A glycosylation may influence synaptic function.", "mechanism": "Reduced SV2A PET signal in WMH-connected cortex may indicate early synaptic loss.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "APP glycosylation affects A\u03b2 generation.", "mechanism": "Elevated A\u03b2 in WMH-connected cortex may predict progression to AD.", "protein": "Beta-amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "Tau glycosylation influences aggregation propensity.", "mechanism": "Tau deposition in WMH-connected cortex may signal early neurodegeneration.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Cerebral small vessel disease", "glycan_involvement": "SV2A glycosylation may modulate synaptic resilience to vascular injury.", "mechanism": "SV2A PET reduction in WMH-connected cortex reflects synaptic loss due to vascular pathology.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Cerebral small vessel disease", "glycan_involvement": "APP glycosylation may interact with vascular factors affecting A\u03b2 clearance.", "mechanism": "A\u03b2 deposition in WMH-connected cortex may be exacerbated by vascular dysfunction.", "protein": "Beta-amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Cerebral small vessel disease", "glycan_involvement": "Tau glycosylation may affect vulnerability to vascular insults.", "mechanism": "Tau accumulation in WMH-connected cortex may be linked to vascular-mediated neurodegeneration.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11715933" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Targeting SV2A glycosylation could modulate synaptic stability.", "mechanism": "SV2A loss in WMH-connected cortex suggests potential for synaptic preservation strategies.", "protein": "SV2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11715933" }, { "confidence": "medium", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "N-glycosylation modulates EGFR stability and signaling in the CNS.", "mechanism": "Downregulation in high ARIA risk profile; may reflect altered signaling or neuroinflammation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Downregulated in high ARIA risk; may be involved in extracellular matrix or synaptic function.", "protein": "CRTAC1", "protein_enriched": { "function": "Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-indu", "gene_name": "ASPN", "glycan_count": 124, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01650EU", "G02030ZB", "G02315DX", "G02815KT", "G03382KH", "G04657PL", "G05049YU", "G05962QB", "G06356OH", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G14972EH", "G14994KB", "G17208MA", "G20210JR", "G20528HD", "G22310AV", "G23505EP", "G23719VF", "G23863VK", "G24954UD", "G25418HZ", "G25451PN", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G31916IQ", "G34617SM", "G34989PA", "G35029YA", "G35253PZ", "G35541EV", "G36379GD", "G37509XX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G45504EY", "G46503DX", "G46524LG", "G46687AB", "G46691LC", "G47644PP", "G50045TK", "G50757KG", "G51640FO", "G57776ZS", "G58087IP", "G59626AS", "G60033FS", "G61256FT", "G63041LO", "G64394MX", "G64409MC", "G65019XG", "G65092SV", "G65184UU", "G66621EA", "G66760KM", "G68490OW", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G72667IM", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G74430RZ", "G76295SF", "G77547TA", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80920RR", "G81198YO", "G81263BG", "G82592ZH", "G83460ZZ", "G83646BJ", "G84452RH", "G84862VB", "G85554PZ", "G86182NS", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88891KO", "G89045VA", "G89098OM", "G90093AU", "G90382BL", "G90659AW", "G90734RJ", "G91636VS", "G92406TI", "G92551JA", "G93718GY", "G94470IW", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "Q9BXN1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Downregulated in high ARIA risk; AXL is involved in microglial activation and phagocytosis.", "protein": "AXL", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell", "gene_name": "AXL", "glycan_count": 14, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G27058EU", "G84452RH", "G11629QQ", "G12793SR", "G15169WU", "G48414YA", "G52527GH", "G60834IK", "G62765YT", "G81263BG", "G89205CJ", "G93656SY", "G90575OW" ], "uniprot_id": "P30530" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "Heavily glycosylated; glycans mediate cell-cell interactions.", "mechanism": "Downregulated in high ARIA risk; involved in neuronal adhesion and signaling.", "protein": "CNTN1", "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "Glycosylation affects secretion and inhibitory activity.", "mechanism": "Downregulated in high ARIA risk; regulates extracellular matrix remodeling.", "protein": "TIMP4", "protein_enriched": { "function": "Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9", "gene_name": "TIMP4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99727" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "high", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "O-glycosylation influences APOE structure and receptor binding.", "mechanism": "APOE4 genotype increases ARIA risk; modulates amyloid clearance.", "protein": "APOE", "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "high", "disease": "Amyloid-related imaging abnormalities (ARIA)", "glycan_involvement": "APP N- and O-glycosylation affects A\u03b2 production and aggregation.", "mechanism": "Low CSF A\u03b242 associated with higher ARIA risk; reflects amyloid deposition.", "protein": "A\u03b242 (APP)", "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation and toxicity.", "mechanism": "Elevated tTau is a marker of neurodegeneration in AD.", "protein": "tTau (MAPT)", "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for AXL function in immune signaling.", "mechanism": "Altered AXL levels reflect microglial response in AD.", "protein": "AXL", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell", "gene_name": "AXL", "glycan_count": 14, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G27058EU", "G84452RH", "G11629QQ", "G12793SR", "G15169WU", "G48414YA", "G52527GH", "G60834IK", "G62765YT", "G81263BG", "G89205CJ", "G93656SY", "G90575OW" ], "uniprot_id": "P30530" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation mediates neuronal adhesion and signaling.", "mechanism": "Altered CNTN1 may impact synaptic integrity in AD.", "protein": "CNTN1", "relationship_type": "biomarker", "source_pmcid": "PMC11716379" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation is essential for its synaptic vesicle localization and function.", "mechanism": "SV2A density loss reflects synaptic loss, which correlates with cognitive impairment and disease progression in AD.", "protein": "Synaptic vesicle glycoprotein 2A", "relationship_type": "biomarker", "source_pmcid": "PMC11716387" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect its synaptic localization and PET detectability.", "mechanism": "Reduced SV2A PET binding indicates synaptic loss associated with tau accumulation in AD.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716481" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "SV2A glycosylation may influence synaptic function and vulnerability.", "mechanism": "Lower SV2A PET binding in A\u03b2+ MCI subjects suggests early synaptic loss.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716481" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "GlycA reflects N-acetyl glycan modifications on acute-phase glycoproteins.", "mechanism": "GlycA is an inflammation marker elevated in AD; decreased levels are associated with reduced inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11716860" }, { "confidence": "high", "disease": "Cognitive Decline", "glycan_involvement": "N-acetyl glycan modifications on circulating glycoproteins.", "mechanism": "Elevated GlycA is associated with increased risk of cognitive decline; reduction indicates lower systemic inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11716860" }, { "confidence": "medium", "disease": "Reduced Brain Volume", "glycan_involvement": "Reflects glycosylation status of acute-phase proteins.", "mechanism": "Higher GlycA levels are linked to reduced brain volume, possibly via chronic inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11716860" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect stability and detection as a biomarker.", "mechanism": "Increased plasma GFAP reflects astrocytic activation and neurodegeneration associated with CAA progression.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "sTREM2 is N-glycosylated; glycosylation modulates secretion and function.", "mechanism": "Elevated plasma sTREM2 indicates microglial activation in CAA pathology.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "YKL-40 is heavily glycosylated; glycosylation is essential for secretion and biomarker utility.", "mechanism": "Increased YKL-40 in plasma reflects neuroinflammation and glial activation in CAA.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "NfL is glycosylated; glycosylation may affect stability and detection.", "mechanism": "Rising NfL in CSF and plasma indicates axonal damage in CAA.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "MMP1 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Decreased plasma MMP1 with age may reflect altered extracellular matrix remodeling in CAA.", "protein": "MMP1", "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "MMP2 is glycosylated; glycosylation modulates enzyme activity.", "mechanism": "Decreased plasma MMP2 with age may indicate reduced matrix degradation in CAA.", "protein": "MMP2", "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "Kallikrein-6 is glycosylated; glycosylation influences secretion and protease activity.", "mechanism": "Age-related changes in plasma kallikrein-6 may reflect neurodegenerative processes in CAA.", "protein": "Kallikrein-6 (neurosin)", "protein_enriched": { "function": "Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein,", "gene_name": "KLK6", "glycan_count": 18, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01659NO", "G03081ER", "G07493GF", "G08146BT", "G15828HX", "G21327TO", "G22208HN", "G28536BG", "G44369QM", "G45495MK", "G53965RU", "G56069TX", "G57818FI", "G68969GZ", "G71146HJ", "G75983OB", "G84452RH", "G92534LG" ], "uniprot_id": "Q92876" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect transport and biomarker properties.", "mechanism": "Decreased albumin index in CSF/plasma suggests blood-brain barrier dysfunction in CAA.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "AD", "glycan_involvement": "GFAP glycosylation may influence biomarker detection.", "mechanism": "Elevated GFAP is associated with astrocytic activation in AD pathology.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "medium", "disease": "AD", "glycan_involvement": "Glycosylation is critical for YKL-40 secretion and function.", "mechanism": "Increased YKL-40 reflects neuroinflammation in AD.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC11716910" }, { "confidence": "high", "disease": "Limb Girdle Muscular Dystrophy (LGMD)", "glycan_involvement": "Defective N-linked glycosylation, especially hypoglycosylation of alpha-dystroglycan in muscle/brain.", "mechanism": "Pathogenic variants impair ER-to-Golgi trafficking and glycosylation, leading to muscle pathology.", "protein": "TRAPPC11", "protein_enriched": { "function": "May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex", "gene_name": "DCAF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WV16" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "Spondyloepiphyseal Dysplasia Tarda (SEDT)", "glycan_involvement": "Impaired secretion of procollagen, a glycoprotein, leads to skeletal dysplasia.", "mechanism": "Variants disrupt procollagen export from ER, affecting skeletal development.", "protein": "TRAPPC2", "protein_enriched": { "function": "May play a role in vesicular transport from endoplasmic reticulum to Golgi", "gene_name": "TRAPPC3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43617" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "Neurodevelopmental Disorder (TRAPPC4)", "glycan_involvement": "Delayed trafficking affects glycoprotein processing in neurons.", "mechanism": "Splice and missense variants cause defective TRAPP complex assembly and trafficking, leading to brain atrophy and epilepsy.", "protein": "TRAPPC4", "protein_enriched": { "function": "Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins (By similarity). Probably acts together with the mo", "gene_name": "BOLA1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y3E2" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "NIBP Syndrome (TRAPPC9)", "glycan_involvement": "Indirect; trafficking defects may affect glycoprotein maturation.", "mechanism": "Loss-of-function variants disrupt NF-kB signaling, causing intellectual disability and brain malformations.", "protein": "TRAPPC9", "protein_enriched": { "function": "Plays a role in primary cilia formation (PubMed:26365339). May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patte", "gene_name": "TAPT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6NXT6" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "Microcephaly (TRAPPC10)", "glycan_involvement": "Defective trafficking may impact glycoprotein processing in neural tissue.", "mechanism": "Frameshift and missense variants impair TRAPP complex assembly, leading to reduced myelination and microcephaly.", "protein": "TRAPPC10", "protein_enriched": { "function": "Enhances DNA synthesis and may play a role in cell proliferation", "gene_name": "HDGFL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3E1" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "TRAPPC2L-related Encephalopathy", "glycan_involvement": "Impaired trafficking affects glycoprotein delivery in neurons.", "mechanism": "Missense/nonsense variants disrupt TRAPP complex formation, causing trafficking defects and neurodevelopmental delay.", "protein": "TRAPPC2L", "protein_enriched": { "function": "Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. Th", "gene_name": "VPS36", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86VN1" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "medium", "disease": "Bardet\u2013Biedl Syndrome (BBS)", "glycan_involvement": "Defective trafficking may affect ciliary glycoproteins.", "mechanism": "Missense variant impairs cilia biogenesis, leading to BBS features.", "protein": "TRAPPC3", "protein_enriched": { "function": "Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network", "gene_name": "TMED3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3Q3" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "TRAPPC6B-related Microcephaly", "glycan_involvement": "Defective trafficking may impact glycoprotein maturation in neurons.", "mechanism": "Splice/nonsense variants cause impaired brain development and neuronal hyperexcitability.", "protein": "TRAPPC6B", "protein_enriched": { "function": "Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in", "gene_name": "STAU1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95793" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "Primary Microcephaly (TRAPPC14)", "glycan_involvement": "Defective trafficking may affect glycoprotein delivery to cilia.", "mechanism": "Truncating variant impairs ciliary vesicle tethering and neuronal proliferation.", "protein": "TRAPPC14 (MAP11)", "protein_enriched": { "function": "Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between c", "gene_name": "RAPGEF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4G8" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "TRAPPC12-related Childhood Encephalopathy", "glycan_involvement": "Impaired glycoprotein trafficking in neurons.", "mechanism": "Variants cause fragmented Golgi and delayed ER-to-Golgi transport, leading to neurological symptoms.", "protein": "TRAPPC12", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y4P6" }, "relationship_type": "causal", "source_pmcid": "PMC11728246" }, { "confidence": "high", "disease": "Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 (MDDGC5)", "glycan_involvement": "Defective O-mannosyl glycosylation of \u03b1-dystroglycan", "mechanism": "FKRP mutations impair glycosylation of \u03b1-dystroglycan, disrupting muscle membrane stability.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy, autosomal recessive 23 (LGMDR23)", "glycan_involvement": "LAMA2 is a heavily glycosylated ECM protein; glycosylation is critical for function.", "mechanism": "LAMA2 mutations disrupt laminin-211, affecting muscle basement membrane integrity.", "protein": "LAMA2", "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "high", "disease": "Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 (MDDGC5)", "glycan_involvement": "O-mannosyl glycosylation of \u03b1-dystroglycan is reduced", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan impairs its binding to ECM proteins like laminin.", "protein": "Dystroglycan (via FKRP)", "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Indirect: dystrophin anchors glycosylated dystroglycan complex", "mechanism": "DMD mutations disrupt dystrophin, destabilizing the dystrophin-glycoprotein complex.", "protein": "DMD (Dystrophin)", "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Muscular dystrophy, congenital, LMNA-related (MDCL)", "glycan_involvement": "None direct", "mechanism": "LMNA mutations affect nuclear envelope stability; not directly glycosylation-related.", "protein": "LMNA", "protein_enriched": { "function": "Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the i", "gene_name": "LMNA", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P02545" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Congenital myopathy 2C (CMYP2C)", "glycan_involvement": "None direct", "mechanism": "ACTA1 mutations disrupt sarcomeric actin function.", "protein": "ACTA1", "protein_enriched": { "function": "Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells", "gene_name": "ACTA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P68133" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Nemaline myopathy 8 (NEM8)", "glycan_involvement": "None direct", "mechanism": "KLHL40 mutations impair sarcomere assembly.", "protein": "KLHL40", "protein_enriched": { "function": "Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase", "gene_name": "KLHL20", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2M5" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Congenital myopathy 1B (CMYP1B)", "glycan_involvement": "None direct", "mechanism": "RYR1 mutations affect calcium release in muscle.", "protein": "RYR1", "protein_enriched": { "function": "Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following", "gene_name": "RYR1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P21817" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Mitochondrial myopathy and ataxia (MMYAT)", "glycan_involvement": "None direct", "mechanism": "MSTO1 mutations impair mitochondrial dynamics.", "protein": "MSTO1", "protein_enriched": { "function": "Involved in the regulation of mitochondrial distribution and morphology (PubMed:17349998, PubMed:28544275, PubMed:28554942). Required for mitochondrial fusion and mitochondrial network formation (PubM", "gene_name": "MSTO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BUK6" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "medium", "disease": "Spastic paraplegia 3A (SPG3A)", "glycan_involvement": "None direct", "mechanism": "ATL1 mutations affect ER morphology and axonal maintenance.", "protein": "ATL1", "protein_enriched": { "function": "Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It facilitates the formation of t", "gene_name": "ATL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF7" }, "relationship_type": "causal", "source_pmcid": "PMC11734487" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (ALG13-CDG)", "glycan_involvement": "Defective N-glycosylation of proteins and lipids.", "mechanism": "Mutation in ALG13 disrupts N-linked glycosylation, leading to multisystem disease.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "high", "disease": "Microcephaly", "glycan_involvement": "Deficient N-glycosylation in neural proteins.", "mechanism": "Impaired glycosylation affects neurodevelopment.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "high", "disease": "Developmental Delay", "glycan_involvement": "Impaired N-glycosylation of neuronal proteins.", "mechanism": "Disrupted glycoprotein function in the CNS.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "medium", "disease": "Hypotonia", "glycan_involvement": "Defective N-glycosylation in neuromuscular proteins.", "mechanism": "Glycosylation defects affect muscle and nerve function.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "medium", "disease": "Hepatomegaly", "glycan_involvement": "Impaired N-glycosylation in hepatic glycoproteins.", "mechanism": "Glycosylation defects disrupt hepatic protein function.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "medium", "disease": "Seizures", "glycan_involvement": "Abnormal N-glycosylation of CNS proteins.", "mechanism": "Defective glycosylation alters neuronal excitability.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC11738639" }, { "confidence": "low", "disease": "Malignant Hyperthermia", "glycan_involvement": "Indirect; glycosylation defects may affect muscle proteins.", "mechanism": "Family history of MH in CDG patient may indicate increased risk.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "biomarker", "source_pmcid": "PMC11738639" }, { "confidence": "high", "disease": "Gaucher disease (GD)", "glycan_involvement": "Glycosylation required for lysosomal targeting and activity.", "mechanism": "Loss-of-function variants cause lysosomal accumulation of glucosylceramide and neurodegeneration.", "protein": "GBA1 (Glucocerebrosidase)", "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Parkinson disease", "glycan_involvement": "Glycosylation affects folding, trafficking, and lysosomal function.", "mechanism": "Variants increase risk; impaired lysosomal degradation of \u03b1-synuclein.", "protein": "GBA1 (Glucocerebrosidase)", "relationship_type": "risk factor/causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Kufs disease (adult-onset NCL)", "glycan_involvement": "Glycosylation required for lysosomal targeting and processing.", "mechanism": "Biallelic variants cause NCL via impaired lysosomal function.", "protein": "CLN11 (Progranulin)", "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Frontotemporal dementia", "glycan_involvement": "Glycosylation affects trafficking and lysosomal delivery.", "mechanism": "Haploinsufficiency impairs lysosomal glucocerebrosidase activity.", "protein": "CLN11 (Progranulin)", "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Niemann-Pick disease type C (NPC)", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Variants block lysosomal cholesterol export, causing neurodegeneration.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Niemann-Pick disease type C (NPC)", "glycan_involvement": "Glycosylation required for stability and lysosomal function.", "mechanism": "Variants impair cholesterol transfer to NPC1, causing lysosomal accumulation.", "protein": "NPC2", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:11125141, PubMed:15937921, PubMed:", "gene_name": "NPC2", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G28681TP", "G41247ZX", "G05049YU", "G06110VR", "G07810QS", "G14669DU", "G18647XP", "G23719VF", "G27915IV", "G31852PQ", "G34989PA", "G37818NZ", "G37995HC", "G43223CG", "G43734MM", "G45504EY", "G46691LC", "G54010QB", "G57317CE", "G57776ZS", "G62765YT", "G65344XH", "G69521XL", "G73027HY", "G80920RR", "G85282JO", "G87661QW", "G89045VA", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "P61916" }, "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation affects lysosomal targeting and enzyme activity.", "mechanism": "Variants reduce lysosomal processing of CLN10, impairing A\u03b242 degradation.", "protein": "CLN5", "protein_enriched": { "function": "Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metapha", "gene_name": "ANLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NQW6" }, "relationship_type": "risk factor", "source_pmcid": "PMC11739831" }, { "confidence": "medium", "disease": "Parkinson disease", "glycan_involvement": "Glycosylation required for lysosomal activity.", "mechanism": "Recombinant CLN10 reduces \u03b1-synuclein aggregation.", "protein": "CLN10 (Cathepsin D)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pa", "gene_name": "CTSD", "glycan_count": 116, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G05724UK", "G06110VR", "G14669DU", "G22573RC", "G26759AS", "G29880MM", "G39188ZX", "G47012YE", "G48414YA", "G50045TK", "G50757KG", "G72735IY", "G74724QE", "G80920RR", "G82463GQ", "G84452RH", "G96416FQ", "G49108TO", "G00406II", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03238UC", "G05049YU", "G08290VR", "G10019LZ", "G10486CT", "G10773YW", "G11314AS", "G11870QZ", "G11911BT", "G12313PD", "G15664MX", "G18647XP", "G20210JR", "G22310AV", "G23294PN", "G23453IV", "G23719VF", "G23863VK", "G23984SE", "G25637MV", "G27058EU", "G27126ED", "G28541PG", "G28681TP", "G29184RN", "G30248BL", "G31852PQ", "G31936TA", "G33609NS", "G34029GR", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37881RL", "G37995HC", "G39446WN", "G40574BA", "G41071NU", "G41247ZX", "G41840AI", "G43223CG", "G45395BF", "G46503DX", "G47644PP", "G48584BU", "G49018RC", "G50282JC", "G51640FO", "G51653BI", "G52527GH", "G56784JY", "G57317CE", "G57888GL", "G59626AS", "G59924QI", "G62765YT", "G62894KT", "G63041LO", "G63381RX", "G64409MC", "G64527OM", "G65092SV", "G66621EA", "G70101JE", "G70223PD", "G70619PT", "G72747WU", "G72787SB", "G73968GN", "G77547TA", "G80223IX", "G83460ZZ", "G84225JN", "G84349RE", "G85269DF", "G85554PZ", "G86880BF", "G88891KO", "G89045VA", "G90575OW", "G90659AW", "G90734RJ", "G90787TS", "G92050GC", "G92275SC", "G92406TI", "G95177YH", "G95865ZB", "G96091TT", "G57321FI", "G43417UB" ], "uniprot_id": "P07339" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Mucopolysaccharidosis II (MPS II)", "glycan_involvement": "N-glycosylation required for lysosomal targeting.", "mechanism": "Variants cause lysosomal glycosaminoglycan accumulation and neurodegeneration.", "protein": "IDS (Iduronate 2-sulfatase)", "protein_enriched": { "function": "Lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate", "gene_name": "IDS", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G83460ZZ", "G28681TP", "G50282JC", "G84349RE", "G92050GC", "G49108TO" ], "uniprot_id": "P22304" }, "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Mucopolysaccharidosis I (MPS I)", "glycan_involvement": "N-glycosylation required for lysosomal targeting.", "mechanism": "Variants cause lysosomal glycosaminoglycan accumulation and neurodegeneration.", "protein": "IDUA (Alpha-L-iduronidase)", "protein_enriched": { "function": "", "gene_name": "IDUA", "glycan_count": 17, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G06110VR", "G74724QE", "G92275SC", "G77653XA", "G09724ZC", "G22768VO", "G23799GS", "G56014GC", "G64527OM", "G66676MI", "G70101JE", "G83161QT", "G83460ZZ", "G89864BN", "G92406TI", "G62765YT" ], "uniprot_id": "P35475" }, "relationship_type": "causal", "source_pmcid": "PMC11739831" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin binds glycosylated beta-dystroglycan; glycosylation critical for DAPC integrity.", "mechanism": "Loss of dystrophin disrupts DAPC, destabilizes muscle membrane, initiates DMD pathology.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Beta-dystroglycan is heavily glycosylated; glycosylation required for laminin binding.", "mechanism": "Loss of dystrophin impairs beta-dystroglycan function, weakening muscle-ECM linkage.", "protein": "Beta-dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin glycosylation mediates ECM interactions.", "mechanism": "DAPC disruption impairs laminin anchoring, contributing to muscle instability.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Some HDAC isoforms are glycosylated, affecting localization/activity.", "mechanism": "HDAC hyperactivity suppresses muscle regeneration, promotes inflammation and fibrosis.", "protein": "Histone deacetylases (HDACs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "NOS membrane localization may depend on glycosylated DAPC components.", "mechanism": "DAPC disassembly displaces NOS, reducing NO signaling and increasing HDAC activity.", "protein": "Nitric oxide synthase (NOS)", "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "MPO is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "MPO levels indicate neutrophil/monocyte/macrophage-driven inflammation in dystrophic muscle.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "MHCI glycosylation modulates immune recognition.", "mechanism": "Upregulated MHCI on muscle fibers marks loss of immune privilege in DMD.", "protein": "MHCI", "relationship_type": "biomarker", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "MHCII glycosylation affects antigen presentation.", "mechanism": "Induced MHCII expression on muscle fibers signals chronic immune activation.", "protein": "MHCII", "relationship_type": "biomarker", "source_pmcid": "PMC11743666" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "FAP surface glycoproteins mediate cell fate and ECM interactions.", "mechanism": "Aberrant FAP activation leads to excess connective tissue and fat cell differentiation.", "protein": "FAP cell surface proteins", "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Syntrophin glycosylation may affect DAPC assembly.", "mechanism": "DAPC disassembly disrupts syntrophin-mediated anchoring of signaling proteins.", "protein": "Syntrophin", "relationship_type": "causal", "source_pmcid": "PMC11743666" }, { "confidence": "high", "disease": "Nephrotic syndrome", "glycan_involvement": "Low sialylation of ANGPTL4 increases pathogenicity; sialylation status modulates glomerular binding and function.", "mechanism": "Podocyte-derived low-sialylated ANGPTL4 disrupts glomerular filtration barrier, induces proteinuria, and podocyte injury.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "high", "disease": "Diabetic kidney disease", "glycan_involvement": "Sialylation modulates ANGPTL4's effect on podocytes; ManNAc (sialic acid precursor) is protective.", "mechanism": "Elevated ANGPTL4 in urine and tissue correlates with albuminuria and renal dysfunction; promotes podocyte injury via integrin-\u03b21/FAK and ROS/NLRP3 pathways.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "medium", "disease": "Lupus nephritis", "glycan_involvement": "Not specified.", "mechanism": "Urinary ANGPTL4 is elevated in active LN; silencing ANGPTL4 reduces proteinuria and inflammation via NLRP3 inflammasome inhibition.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL4 is upregulated in ccRCC; promotes tumor growth, angiogenesis, and redox balance; knockdown suppresses proliferation.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "medium", "disease": "Hyperlipidemia-induced renal injury", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL4 upregulation in high-fat models promotes proteinuria and podocyte injury; knockout reduces renal damage.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11747783" }, { "confidence": "low", "disease": "Acute kidney injury", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL4 is upregulated in AKI models; may regulate LPL activity and contribute to tubular injury.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11747783" }, { "confidence": "low", "disease": "IgA nephropathy", "glycan_involvement": "Not specified.", "mechanism": "Plasma and urinary ANGPTL4 levels correlate with podocyte damage and disease severity.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11747783" }, { "confidence": "low", "disease": "Chronic kidney disease/interstitial fibrosis", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL4 upregulation correlates with fibrosis; modulates HIF-1\u03b1 loop and fibrotic progression.", "protein": "Angiopoietin-like protein 4", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NXA8" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL3 deletion or inhibition ameliorates podocyte injury and inflammation via NLRP3 pathway.", "protein": "Angiopoietin-like protein 3", "protein_enriched": { "function": "Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the traffic", "gene_name": "ANGPTL3", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G62765YT", "G63381RX", "G90659AW", "G49108TO", "G29068FM", "G53434XO", "G28681TP", "G75983OB", "G08918WF", "G40574BA", "G59626AS", "G65184UU", "G70619PT", "G72747WU", "G72790NZ" ], "uniprot_id": "Q9Y5C1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11747783" }, { "confidence": "low", "disease": "Renal cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "ANGPTL2 deficiency promotes CD8+ T-cell infiltration and delays tumor progression.", "protein": "Angiopoietin-like protein 2", "protein_enriched": { "function": "Induces sprouting in endothelial cells through an autocrine and paracrine action", "gene_name": "ANGPTL2", "glycan_count": 54, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G04657PL", "G05962QB", "G22310AV", "G23863VK", "G25418HZ", "G27058EU", "G27126ED", "G28541PG", "G31852PQ", "G41071NU", "G45395BF", "G46691LC", "G57776ZS", "G60177UT", "G62765YT", "G63136LV", "G70441OD", "G79666IR", "G80223IX", "G80479JV", "G80920RR", "G82830MN", "G84452RH", "G87123QX", "G90659AW", "G93718GY", "G01650EU", "G02886BB", "G06110VR", "G10486CT", "G10488MI", "G10819WX", "G15664MX", "G18647XP", "G20706XG", "G27947YN", "G37399XV", "G39446WN", "G40926MX", "G42124LM", "G47644PP", "G47950XN", "G59626AS", "G60033FS", "G60834IK", "G63041LO", "G70619PT", "G72747WU", "G86880BF", "G95865ZB", "G57321FI", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKU9" }, "relationship_type": "protective", "source_pmcid": "PMC11747783" }, { "confidence": "high", "disease": "Saul\u2013Wilson syndrome (SWS)", "glycan_involvement": "Sialylation of N-glycan chains is normal; glycosylation machinery is affected via Golgi trafficking.", "mechanism": "Missense mutation (p.G512R) in COG4 alters Golgi retrograde transport, leading to SWS phenotype (blue sclera, cataract, primordial dwarfism).", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type IIJ (CDG-IIJ)", "glycan_involvement": "Defective sialylation of N-glycan chains due to Golgi dysfunction.", "mechanism": "Missense mutation (p.R729W) in COG4 disrupts Golgi retrograde transport, causing defective glycosylation and multisystemic symptoms.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type IIX (CDG-IIX)", "glycan_involvement": "Impaired N-glycosylation due to Golgi trafficking defects.", "mechanism": "Missense mutation (p.L769R) in COG4 impairs Golgi function, leading to glycosylation defects and systemic manifestations.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "medium", "disease": "Bilateral congenital cataract", "glycan_involvement": "Disrupted glycosylation of lens proteins due to Golgi dysfunction.", "mechanism": "COG4 missense variants (p.Y714F, p.G512R) are associated with cataract formation, possibly via altered Golgi trafficking and glycoprotein processing.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "medium", "disease": "Psychomotor retardation", "glycan_involvement": "Defective glycosylation of neuronal proteins.", "mechanism": "COG4 variants (e.g., p.Y714F, p.R729W) lead to neurological symptoms via impaired glycoprotein processing in the CNS.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Saul\u2013Wilson syndrome (SWS)", "glycan_involvement": "Glycosylation machinery is affected but sialylation is preserved.", "mechanism": "COG4 p.G512R variant is a diagnostic marker for SWS.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type IIJ (CDG-IIJ)", "glycan_involvement": "Defective N-glycan sialylation.", "mechanism": "COG4 p.R729W variant is a diagnostic marker for CDG-IIJ.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type IIX (CDG-IIX)", "glycan_involvement": "Impaired N-glycosylation.", "mechanism": "COG4 p.L769R variant is a diagnostic marker for CDG-IIX.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11751923" }, { "confidence": "medium", "disease": "Bilateral congenital cataract", "glycan_involvement": "Potential disruption of glycosylation/phosphorylation cross-talk in lens proteins.", "mechanism": "COG4 p.Y714F variant found in patient with bilateral congenital cataract; likely disrupts post-translational phosphorylation and glycoprotein processing.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation (general)", "glycan_involvement": "Global impairment of N-glycosylation pathways.", "mechanism": "COG4 mutations impair Golgi trafficking, leading to broad glycosylation defects.", "protein": "COG4", "protein_enriched": { "function": "Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132)", "gene_name": "COG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G94459LH" ], "uniprot_id": "Q9H9E3" }, "relationship_type": "causal", "source_pmcid": "PMC11751923" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "O-mannosylation critical for function; hypoglycosylation impairs ECM binding.", "mechanism": "Loss of glycosylated dystroglycan destabilizes DGC, leading to muscle degeneration.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Becker Muscular Dystrophy (BMD)", "glycan_involvement": "Glycosylation affects membrane localization and DGC stability.", "mechanism": "SGCD upregulated in BMD, possibly as compensatory response; also linked to LGMD.", "protein": "Delta-sarcoglycan (SGCD)", "protein_enriched": { "function": "Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix", "gene_name": "SGCD", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G10486CT", "G28541PG", "G31852PQ", "G39446WN", "G41247ZX", "G57776ZU", "G59626AS", "G88891KO", "G95865ZB" ], "uniprot_id": "Q92629" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Potential glycosylation modulates sarcomere assembly.", "mechanism": "Decreased MYOM2 abundance reflects sarcomere damage and muscle degeneration.", "protein": "Myomesin-2 (MYOM2)", "protein_enriched": { "function": "Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent", "gene_name": "MYOM2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54296" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may regulate Z-disc protein interactions.", "mechanism": "Reduced MYOZ2 correlates with Z-disc disruption and muscle weakness.", "protein": "Myozenin-2 (MYOZ2)", "protein_enriched": { "function": "Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the s", "gene_name": "MYOZ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPC6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may affect protein stability and localization.", "mechanism": "RFFL upregulated; promotes ubiquitination and degradation of muscle proteins, contributing to pathology.", "protein": "E3 ubiquitin-protein ligase rififylin (RFFL)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination o", "gene_name": "RFFL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZ73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation modulates ER retention and calcium binding.", "mechanism": "Upregulated calreticulin linked to ER stress and calcium dysregulation in DMD muscle.", "protein": "Calreticulin", "protein_enriched": { "function": "", "gene_name": "CALR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7P0T861" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation critical for collagen fibril formation and ECM structure.", "mechanism": "Increased COL14A1 reflects fibrosis and ECM remodeling in DMD.", "protein": "Collagen alpha-1(XIV) chain (COL14A1)", "protein_enriched": { "function": "Plays an adhesive role by integrating collagen bundles. It is probably associated with the surface of interstitial collagen fibrils via COL1. The COL2 domain may then serve as a rigid arm which sticks", "gene_name": "COL14A1", "glycan_count": 107, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G43417UB", "G29068FM", "G27391WQ", "G02886BB", "G04657PL", "G05049YU", "G07246CJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G12313PD", "G23719VF", "G27058EU", "G27126ED", "G27915IV", "G31852PQ", "G34989PA", "G36379GD", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G57776ZS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70441OD", "G72790NZ", "G73968GN", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G83646BJ", "G87661QW", "G90382BL", "G90659AW", "G92551JA", "G95177YH", "G01160VV", "G26506TX", "G84452RH", "G92135MA", "G98611JV", "G85435DN", "G49108TO", "G57321FI", "G00912UN", "G06356OH", "G08918WF", "G10846ZT", "G23505EP", "G48414YA", "G59626AS", "G61256FT", "G70223PD", "G70619PT", "G35029YA", "G53434XO", "G57317CE", "G73004SD", "G01485JJ", "G03382KH", "G10488MI", "G14972EH", "G14994KB", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G25418HZ", "G25451PN", "G29299MO", "G31986NC", "G35253PZ", "G37509XX", "G39471UU", "G43669FQ", "G43734MM", "G43769HG", "G46687AB", "G47950XN", "G49755GI", "G51640FO", "G63041LO", "G65092SV", "G72667IM", "G77669RF", "G80223IX", "G81198YO", "G84862VB", "G86182NS", "G90734RJ", "G91636VS" ], "uniprot_id": "Q05707" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "low", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may influence nuclear-cytoplasmic trafficking.", "mechanism": "Decreased XPO1 impairs nuclear export, affecting muscle cell transcriptional regulation.", "protein": "Exportin-1 (XPO1)", "protein_enriched": { "function": "", "gene_name": "XPO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7I2V2S3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Congenital Myopathy", "glycan_involvement": "Glycosylation affects actin binding and filament stability.", "mechanism": "Decreased TPM3 in BMD associated with congenital myopathy and impaired actin regulation.", "protein": "Tropomyosin alpha-3 chain (TPM3)", "protein_enriched": { "function": "", "gene_name": "TPM3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06753-5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "medium", "disease": "Congenital Myopathy", "glycan_involvement": "Glycosylation may regulate filament assembly.", "mechanism": "Reduced LMOD3 in BMD linked to defective actin filament elongation and muscle weakness.", "protein": "Leiomodin-3 (LMOD3)", "protein_enriched": { "function": "Essential for the organization of sarcomeric actin thin filaments in skeletal muscle (PubMed:25250574). Increases the rate of actin polymerization (PubMed:25250574)", "gene_name": "LMOD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q0VAK6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11770181" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Impaired glycosylation leads to ER retention and reduced plasma membrane expression, exacerbating loss of function.", "mechanism": "Loss-of-function mutations or downregulation of KCC2 impair Cl\u2212 extrusion, leading to compromised GABAergic inhibition and increased seizure susceptibility.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Mature N-glycosylation correlates with increased membrane abundance and function.", "mechanism": "Enhancing KCC2 activity or surface expression can suppress seizures by restoring Cl\u2212 homeostasis.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11774852" }, { "confidence": "medium", "disease": "Brain tumors", "glycan_involvement": "Downregulation may affect glycosylation and trafficking.", "mechanism": "Brain tumors downregulate KCC2 expression, increasing risk of epileptic seizures.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Likely impacts glycosylation and membrane targeting.", "mechanism": "Ischemic stroke reduces KCC2 expression, leading to impaired Cl\u2212 extrusion and increased seizure risk.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "medium", "disease": "Brain injury", "glycan_involvement": "May disrupt glycosylation and trafficking.", "mechanism": "Brain injury downregulates KCC2, compromising Cl\u2212 homeostasis and increasing seizure susceptibility.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Mature glycosylation indicates functional KCC2; immature glycosylation correlates with dysfunction.", "mechanism": "Mutations in KCC2 are associated with epilepsy; glycosylation status may serve as a biomarker for functional transporter.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "biomarker", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Immature N-glycosylation (ER-type) prevents plasma membrane localization.", "mechanism": "Specific CTD mutations cause ER retention due to misfolding and immature glycosylation, leading to loss of function.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Mature N-glycosylation present, but kinetic activity lost.", "mechanism": "Some CTD mutations result in mature glycosylation and normal membrane expression but still abolish transporter activity, indicating independent regulation of function and trafficking.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Enhanced activity correlates with mature N-glycosylation and increased membrane abundance.", "mechanism": "Gain-of-function CTD mutations (e.g., B8, C1) enhance Cl\u2212 extrusion and may protect against hyperexcitability.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "protective", "source_pmcid": "PMC11774852" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Promoting mature N-glycosylation enhances functional expression.", "mechanism": "Targeting glycosylation pathways or CTD motifs may restore KCC2 function and membrane localization in disease.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11774852" }, { "confidence": "high", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Surface glycosylation aids immune evasion.", "mechanism": "M protein mediates immune evasion and adhesion, facilitating invasive infection.", "protein": "M protein (emm)", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "high", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Glycosylation may affect secretion and immune recognition.", "mechanism": "SPE-G acts as a superantigen, triggering excessive immune response.", "protein": "SPE-G", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Glycosylation may modulate activity and stability.", "mechanism": "SME-Z is a superantigen, promoting T-cell activation and cytokine storm.", "protein": "SME-Z", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Potential glycosylation influences immunogenicity.", "mechanism": "SPE-H contributes to immune dysregulation.", "protein": "SPE-H", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Glycosylation may affect secretion.", "mechanism": "SPE-I acts as a superantigen, exacerbating inflammation.", "protein": "SPE-I", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Necrotizing fasciitis", "glycan_involvement": "Glycosylation may modulate toxin potency.", "mechanism": "SPE-A is linked to severe tissue damage via superantigen activity.", "protein": "SPE-A", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "high", "disease": "Skin and soft tissue infection", "glycan_involvement": "Surface glycosylation impacts tissue adherence.", "mechanism": "Specific M protein serotypes are associated with skin/soft tissue tropism.", "protein": "M protein (emm1, emm12)", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "SPE-J is a superantigen contributing to systemic inflammation.", "protein": "SPE-J", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal (GAS) disease", "glycan_involvement": "Glycosylation may influence resistance gene expression.", "mechanism": "Presence of resistance genes in these serotypes marks invasive potential.", "protein": "M protein (emm11, emm49)", "relationship_type": "biomarker", "source_pmcid": "PMC11776779" }, { "confidence": "medium", "disease": "Necrotizing fasciitis", "glycan_involvement": "Glycosylation may affect toxin stability.", "mechanism": "SPE-G superantigen activity may contribute to tissue destruction.", "protein": "SPE-G", "relationship_type": "causal", "source_pmcid": "PMC11776779" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation is essential for P-gp folding and membrane localization.", "mechanism": "P-gp mediates efflux of antiretroviral drugs, affecting their pharmacokinetics.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic target", "source_pmcid": "PMC11777774" }, { "confidence": "high", "disease": "Multidrug-resistant HIV-1", "glycan_involvement": "Glycosylation modulates P-gp stability and function.", "mechanism": "Overexpression of P-gp contributes to drug resistance by reducing intracellular drug concentrations.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC11777774" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation affects CYP3A enzyme activity and substrate specificity.", "mechanism": "CYP3A metabolizes antiretroviral drugs, influencing their efficacy and toxicity.", "protein": "Cytochrome P450 3A (CYP3A)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847,", "gene_name": "CYP3A4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08684" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC11777774" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation is important for UGT1A1 stability and localization.", "mechanism": "UGT1A1 mediates glucuronidation of antiretrovirals, impacting drug clearance.", "protein": "UDP-glucuronosyltransferase 1A1 (UGT1A1)", "protein_enriched": { "function": "UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, ", "gene_name": "UGT1A1", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G14669DU", "G39188ZX" ], "uniprot_id": "P22309" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC11777774" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation status may influence biomarker reliability.", "mechanism": "P-gp expression levels can predict response to antiretroviral therapy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC11777774" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "AP is a glycoprotein; glycosylation affects its stability and secretion, but specific glycan changes in COVID-19 are not described.", "mechanism": "Elevated AP at admission is associated with increased mortality in COVID-19 patients.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "AST is glycosylated; glycosylation may influence its serum levels, but direct COVID-19 glycan effects are not detailed.", "mechanism": "Severely elevated AST at admission predicts higher mortality in COVID-19 patients.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ALT is glycosylated; glycosylation may affect its release, but no COVID-19-specific glycan data provided.", "mechanism": "Severely elevated ALT is associated with mortality in COVID-19 patients without prior liver disease or remdesivir use.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "high", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Glycosylation is essential for AP function; no COVID-19-specific glycan changes reported.", "mechanism": "Abnormal AP indicates liver dysfunction, which is common in severe COVID-19.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "high", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Glycosylation may affect AST stability; no direct evidence for COVID-19-specific glycan changes.", "mechanism": "Elevated AST reflects hepatic injury in COVID-19.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "ALT glycosylation may influence its serum levels; no COVID-19-specific data.", "mechanism": "ALT elevation is a marker of liver injury in COVID-19.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11777833" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Capsular polysaccharide is a glycan-rich structure critical for virulence and immune evasion.", "mechanism": "Capsular polysaccharide enables S. pneumoniae to evade host immune response, leading to invasive infection.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "Glycosylation of capsule is essential for pathogenicity.", "mechanism": "Capsular polysaccharide mediates resistance to phagocytosis, facilitating lung infection.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "medium", "disease": "Pneumonia with empyema", "glycan_involvement": "Serotype-specific glycan modifications affect disease severity.", "mechanism": "Certain serotypes with specific capsular glycan structures are associated with severe pneumonia and empyema.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Glycosylation of capsule prevents complement-mediated killing.", "mechanism": "Capsular polysaccharide allows S. pneumoniae to survive in bloodstream.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "Specific glycan structures facilitate CNS invasion.", "mechanism": "Capsular glycoprotein enables crossing of blood-brain barrier.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "medium", "disease": "Peritonitis", "glycan_involvement": "Glycosylation aids in immune evasion.", "mechanism": "Capsular polysaccharide protects bacteria in peritoneal cavity.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Vaccine-induced antibodies recognize specific glycan epitopes.", "mechanism": "Capsular polysaccharide is targeted by conjugate vaccines (PCV13, PCV20).", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "Glycan antigens are basis for vaccine serotype coverage.", "mechanism": "Vaccines targeting capsular glycoproteins reduce CAP incidence.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Quellung reaction detects glycan epitopes.", "mechanism": "Serotype-specific capsular glycoproteins are used for diagnosis and epidemiology.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "biomarker", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Glycan conjugation is essential for immunogenicity.", "mechanism": "Vaccination with conjugated capsular glycoproteins induces protective immunity.", "protein": "Streptococcus pneumoniae capsular polysaccharide", "relationship_type": "protective", "source_pmcid": "PMC11778145" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "gp120 is heavily glycosylated, which affects its antigenicity and immune evasion.", "mechanism": "gp120 is expressed on HIV-1 infected cells and serves as a target for molecular imaging to identify viral reservoirs.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778633" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation shields gp120 from immune recognition, influencing targeting strategies.", "mechanism": "gp120 is targeted by nanobodies and antibodies for imaging and potential therapeutic intervention.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11778633" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "CXCL10 is glycosylated, which may affect its stability and receptor interactions.", "mechanism": "Elevated CXCL10 levels in MASLD patients with sCAP indicate heightened inflammatory response.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "IL-10 glycosylation can modulate secretion and activity.", "mechanism": "Higher IL-10 in MASLD patients with sCAP suggests altered anti-inflammatory regulation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "TNF-\u03b1 glycosylation may influence receptor binding and bioactivity.", "mechanism": "Increased TNF-\u03b1 in MASLD with sCAP reflects enhanced pro-inflammatory signaling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "TGF-\u03b21 glycosylation affects folding and secretion.", "mechanism": "Lower TGF-\u03b21 in MASLD with sCAP may indicate impaired immunoregulatory function.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "low", "disease": "sCAP (without MASLD)", "glycan_involvement": "IL-2 glycosylation impacts receptor interaction.", "mechanism": "IL-2 increases only in sCAP patients without MASLD, suggesting differential immune activation.", "protein": "IL-2", "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "low", "disease": "sCAP", "glycan_involvement": "IL-6 glycosylation modulates stability and activity.", "mechanism": "IL-6 decreases over time in both groups, reflecting resolution of inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "low", "disease": "sCAP", "glycan_involvement": "IL-8 glycosylation affects chemotactic function.", "mechanism": "IL-8 decreases in both groups, indicating reduced neutrophil recruitment.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "low", "disease": "sCAP", "glycan_involvement": "CCL2 glycosylation influences receptor binding.", "mechanism": "CCL2 decreases in both groups, marking reduced monocyte recruitment.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "biomarker", "source_pmcid": "PMC11778744" }, { "confidence": "high", "disease": "COVID-19-Associated Pulmonary Aspergillosis (CAPA)", "glycan_involvement": "KL-6 is a mucin-type glycoprotein; its glycosylation is essential for its secretion and detection as a biomarker.", "mechanism": "Elevated serum KL-6 reflects damage to type II alveolar epithelial cells, which is associated with increased risk of CAPA in critically ill COVID-19 patients.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11779108" }, { "confidence": "high", "disease": "Mortality in critically ill COVID-19 patients", "glycan_involvement": "Glycosylation of KL-6 enables its release into circulation and detection in serum.", "mechanism": "Higher KL-6 levels are associated with increased 30-day mortality, indicating severe epithelial injury.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11779108" }, { "confidence": "high", "disease": "Respiratory epithelial damage", "glycan_involvement": "Mucin-type glycosylation is critical for KL-6's structure and function as a damage marker.", "mechanism": "KL-6 is released from damaged type II alveolar cells, serving as a marker for epithelial injury.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11779108" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation facilitates KL-6's stability and detectability in serum.", "mechanism": "KL-6 levels rise in severe COVID-19 due to alveolar epithelial injury.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11779108" }, { "confidence": "medium", "disease": "Enterococcal infection", "glycan_involvement": "Glycosylation affects adhesion and immune evasion.", "mechanism": "Surface glycoproteins mediate host-pathogen interactions and colonization.", "protein": "Enterococcal surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11779418" }, { "confidence": "high", "disease": "Vancomycin-resistant enterococcal infection (VRE)", "glycan_involvement": "Glycan modifications change cell wall structure and antibiotic susceptibility.", "mechanism": "Altered glycoproteins in cell wall reduce vancomycin binding, conferring resistance.", "protein": "Vancomycin resistance-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11779418" }, { "confidence": "high", "disease": "Rafiq Syndrome (MAN1B1-CDG)", "glycan_involvement": "Defective N-glycosylation in the Golgi apparatus affects glycoprotein maturation.", "mechanism": "Loss-of-function mutations in MAN1B1 impair N-glycan trimming, leading to multisystemic symptoms.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "medium", "disease": "Hyperekplexia", "glycan_involvement": "Altered N-glycosylation may disrupt glycoprotein function in neural circuits.", "mechanism": "MAN1B1 mutation may affect glycoproteins involved in inhibitory neurotransmission, leading to exaggerated startle response.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal (novel association)", "source_pmcid": "PMC11781345" }, { "confidence": "medium", "disease": "Feeding difficulty (in Rafiq Syndrome)", "glycan_involvement": "Defective N-glycosylation impacts neuromuscular function.", "mechanism": "Impaired glycoprotein synthesis affects muscle groups involved in sucking/swallowing.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Hyperekplexia", "glycan_involvement": "Glycosylation may affect receptor trafficking and function.", "mechanism": "Mutations in GLRA1 disrupt glycinergic neurotransmission, causing startle disease.", "protein": "GLRA1", "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Hyperekplexia", "glycan_involvement": "Glycosylation influences transporter stability and localization.", "mechanism": "Mutations impair glycine reuptake, leading to defective inhibitory signaling.", "protein": "SLC6A5", "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Hyperekplexia", "glycan_involvement": "Glycosylation modulates receptor assembly and function.", "mechanism": "GLRB mutations affect glycine receptor function, contributing to hyperekplexia.", "protein": "GLRB", "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Global N-glycosylation defect.", "mechanism": "PMM2 deficiency impairs N-glycan precursor synthesis, causing multisystemic symptoms.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "ALG1-CDG", "glycan_involvement": "Defective N-glycosylation.", "mechanism": "ALG1 mutations disrupt early N-glycan assembly, leading to severe feeding difficulties.", "protein": "ALG1", "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Global developmental delay (in Rafiq Syndrome)", "glycan_involvement": "Defective glycoprotein maturation in neural tissues.", "mechanism": "Impaired N-glycan processing affects neural development.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Hypotonia (in Rafiq Syndrome)", "glycan_involvement": "N-glycosylation defects in muscle and neural glycoproteins.", "mechanism": "Defective glycoprotein synthesis impacts muscle tone.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC11781345" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation, STT3A type (STT3A-CDG)", "glycan_involvement": "Defective N-glycosylation due to OST-A dysfunction.", "mechanism": "Heterozygous pathogenic variants in STT3A reduce protein stability and catalytic activity, impairing N-glycosylation of multiple glycoproteins.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "high", "disease": "Intellectual Disability", "glycan_involvement": "Defective N-glycosylation of neural glycoproteins.", "mechanism": "Impaired N-glycosylation affects neural development and function.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Skeletal Abnormalities", "glycan_involvement": "Impaired glycosylation of bone matrix proteins.", "mechanism": "Reduced N-glycosylation disrupts bone development and mineralization.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Epileptiform Abnormalities", "glycan_involvement": "Abnormal glycosylation of neuronal membrane proteins.", "mechanism": "Defective N-glycosylation alters neuronal excitability and synaptic function.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Distinctive Facial Features", "glycan_involvement": "Defective glycosylation of developmental glycoproteins.", "mechanism": "Impaired N-glycosylation affects craniofacial development.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Short Stature", "glycan_involvement": "Impaired glycosylation of growth-related glycoproteins.", "mechanism": "Reduced N-glycosylation impacts growth factor signaling.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation, STT3A type (STT3A-CDG)", "glycan_involvement": "OST-A-dependent N-glycosylation of CD107a.", "mechanism": "Decreased CD107a expression in NK cells reflects defective N-glycosylation due to STT3A dysfunction.", "protein": "CD107a (LAMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Abnormal Locomotion and Social Behavior", "glycan_involvement": "Defective glycosylation of synaptic proteins.", "mechanism": "Impaired N-glycosylation affects neural circuits controlling behavior.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "medium", "disease": "Craniofacial Dysmorphology", "glycan_involvement": "Defective glycosylation of cartilage matrix proteins.", "mechanism": "Impaired N-glycosylation disrupts craniofacial cartilage and bone development.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "high", "disease": "Dominant Inheritance of STT3A-CDG", "glycan_involvement": "Partial loss of N-glycosylation capacity.", "mechanism": "Heterozygous missense variants in STT3A can cause disease via dominant negative or haploinsufficiency effects.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC11786438" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dp427 interacts with glycosylated dystroglycans; glycosylation critical for complex stability.", "mechanism": "Loss of Dp427 disrupts sarcolemma stability in muscle and GABAergic synaptic function in brain.", "protein": "Dystrophin (Dp427)", "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Anxiety disorders", "glycan_involvement": "Glycosylated dystroglycans mediate synaptic anchoring; loss disrupts inhibitory synapses.", "mechanism": "Dp427 deficiency reduces GABA_A receptor clustering, leading to amygdala dysfunction and heightened anxiety/fear.", "protein": "Dystrophin (Dp427)", "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "medium", "disease": "Autism spectrum disorder (ASD)", "glycan_involvement": "Glycosylation of dystroglycans required for synaptic complex formation.", "mechanism": "Loss of Dp427 alters GABAergic signaling and synaptic plasticity, contributing to ASD-like behaviors.", "protein": "Dystrophin (Dp427)", "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "Dp140 interacts with glycosylated synaptic proteins; glycosylation status influences localization.", "mechanism": "Dp140 loss during neurodevelopment impairs glutamatergic transmission and cognitive function.", "protein": "Dystrophin (Dp140)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-7" }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "medium", "disease": "Autism spectrum disorder (ASD)", "glycan_involvement": "Glycosylation of interacting partners (e.g., dystroglycans) modulates synaptic effects.", "mechanism": "Combined loss of Dp427 and Dp140 increases ASD risk via impaired glutamatergic signaling.", "protein": "Dystrophin (Dp140)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-7" }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "Dp71 interacts with glycosylated dystroglycans and AQP4; glycosylation affects complex assembly.", "mechanism": "Dp71 deficiency in astrocytes disrupts neurovascular coupling and cognitive function.", "protein": "Dystrophin (Dp71)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-8" }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "medium", "disease": "Working memory/executive dysfunction", "glycan_involvement": "Glycosylation of dystroglycans and AQP4 modulates Dp71 complex stability.", "mechanism": "Loss of Dp71 impairs astrocyte function, affecting working memory and cognitive flexibility.", "protein": "Dystrophin (Dp71)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-8" }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation essential for \u03b2-dystroglycan function and dystrophin binding.", "mechanism": "Loss of dystrophin disrupts \u03b2-dystroglycan glycoprotein complex, destabilizing muscle and synaptic membranes.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosyl glycosylation required for \u03b1-dystroglycan function.", "mechanism": "\u03b1-dystroglycan glycosylation is critical for extracellular matrix binding; loss of dystrophin impairs this interaction.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11790952" }, { "confidence": "medium", "disease": "Autism spectrum disorder (ASD)", "glycan_involvement": "N-glycosylation of NLGN2 modulates synaptic localization and function.", "mechanism": "Dystrophin complex disruption impairs NLGN2-mediated GABAergic synapse formation, contributing to ASD.", "protein": "Neuroligin-2 (NLGN2)", "protein_enriched": { "function": "Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its ", "gene_name": "NLGN1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G80920RR", "G57321FI" ], "uniprot_id": "Q8N2Q7" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11790952" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycosylated dystroglycan to link cytoskeleton to ECM.", "mechanism": "Mutations in the dystrophin gene lead to loss of dystrophin protein, destabilizing muscle cell membranes.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Alpha-dystroglycan is heavily glycosylated; glycosylation is essential for laminin binding.", "mechanism": "Loss of dystrophin disrupts dystroglycan complex, weakening sarcolemma and promoting muscle necrosis.", "protein": "Dystroglycan (alpha/beta)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Sarcoglycans are glycoproteins; glycosylation affects membrane stability.", "mechanism": "Altered sarcoglycan expression destabilizes the dystrophin-glycoprotein complex.", "protein": "Sarcoglycans", "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Laminin-2 is a glycoprotein; glycosylation modulates ECM interactions.", "mechanism": "Dystrophin\u2019s cysteine-rich domain interacts with laminin-2 via dystroglycan; disruption impairs ECM-cytoskeleton linkage.", "protein": "Laminin-2", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMB1", "glycan_count": 135, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G10486CT", "G10488MI", "G11314AS", "G15664MX", "G18647XP", "G20706XG", "G23719VF", "G23863VK", "G27058EU", "G28541PG", "G29184RN", "G31852PQ", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G43669FQ", "G45395BF", "G46691LC", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G77669RF", "G79666IR", "G80920RR", "G84452RH", "G88520YF", "G90659AW", "G92050GC", "G01160VV", "G02030ZB", "G05724UK", "G05962QB", "G06110VR", "G07246CJ", "G07755XJ", "G08918WF", "G10819WX", "G13131HA", "G14260UH", "G14972EH", "G16125XL", "G20312EM", "G20528HD", "G24528MX", "G25451PN", "G27126ED", "G27915IV", "G28622IK", "G29545VG", "G30970QQ", "G34617SM", "G35541EV", "G36379GD", "G37412TK", "G39188ZX", "G39471UU", "G40574BA", "G40834TG", "G43223CG", "G45526EA", "G48414YA", "G49755GI", "G50856PC", "G51640FO", "G52131KU", "G53075ES", "G55132BD", "G57776ZS", "G57888GL", "G58954YZ", "G60834IK", "G62894KT", "G64394MX", "G66760KM", "G68490OW", "G70223PD", "G70232NH", "G72797UR", "G73968GN", "G76295SF", "G78787DI", "G80075MS", "G80479JV", "G81263BG", "G81637OR", "G82443XX", "G83633GK", "G83646BJ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G92135MA", "G92275SC", "G93718GY", "G95046LV", "G95177YH", "G96577RX", "G98611JV", "G49108TO", "G11101UV", "G22310AV", "G26436YP", "G75983OB", "G57321FI", "G13694XX", "G71560PC", "G89205CJ", "G38663NM", "G08290VR", "G25418HZ", "G33791AF", "G80223IX", "G83460ZZ" ], "uniprot_id": "P07942" }, "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "medium", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "O-mannosyl glycosylation required for laminin binding; loss leads to cardiac dysfunction.", "mechanism": "Defective glycosylation of alpha-dystroglycan impairs cardiac muscle integrity.", "protein": "Dystroglycan (alpha)", "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "medium", "disease": "Respiratory failure in DMD", "glycan_involvement": "Indirect via dystrophin-glycoprotein complex disruption.", "mechanism": "Dystrophin deficiency weakens respiratory muscles, leading to failure.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11800030" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Therapeutic strategies target glycosylation pathways.", "mechanism": "Restoring glycosylation of alpha-dystroglycan may improve muscle function.", "protein": "Dystroglycan (alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11800030" }, { "confidence": "high", "disease": "Iron loading-associated amyloid-\u03b2 cytotoxicity", "glycan_involvement": "Sialylation with Neu5Gc vs Neu5Ac alters transferrin function.", "mechanism": "Neu5Gc-modified transferrin exacerbates amyloid-\u03b2 cytotoxicity; Neu5Ac-modified transferrin is protective.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "Abnormal brain development", "glycan_involvement": "Polysialylation (polySia) with Neu5Gc alters NCAM function.", "mechanism": "Neu5Gc incorporation disrupts PSA degradation and BDNF release, impairing synaptic plasticity and development.", "protein": "NCAM (PSA-NCAM)", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "medium", "disease": "Memory loss", "glycan_involvement": "Sialylation with Neu5Gc vs Neu5Ac impacts ganglioside function.", "mechanism": "Neu5Gc disrupts normal Neu5Ac function in GM1, affecting synaptic transmission and memory.", "protein": "Ganglioside GM1", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "Abnormal axonal myelination", "glycan_involvement": "Abnormal sialylation with Neu5Gc impairs myelin structure.", "mechanism": "Neu5Gc accumulation leads to reduced myelin proteins, myelin thickness, and axonal myelination.", "protein": "Myelin proteins", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease (AD)", "glycan_involvement": "Neu5Gc incorporation into glycoproteins disrupts normal sialylation.", "mechanism": "Neu5Gc-related sialic acid dysfunction leads to abnormal sialylation and increased AD risk.", "protein": "Sialylated glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Neu5Gc as xenoantigen in glycoproteins triggers autoimmune response.", "mechanism": "Anti-Neu5Gc antibodies target Neu5Gc-incorporated glycoproteins in CNS, damaging BBB and myelin.", "protein": "Sialylated glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Sialylation with Neu5Gc alters microglial function.", "mechanism": "Neu5Gc-modified glycoproteins resist sialidase, leading to over-activated microglial phagocytosis and inflammation.", "protein": "Microglial cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "medium", "disease": "Impaired brain connectivity", "glycan_involvement": "Abnormal sialylation with Neu5Gc impairs cell\u2013cell interactions.", "mechanism": "Neu5Gc incorporation disrupts sialic acid structure, affecting neuronal communication and connectivity.", "protein": "Sialylated glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "Reproductive incompatibility (reduced fertility)", "glycan_involvement": "GPI-anchored glycoprotein with Neu5Gc as antigen.", "mechanism": "Neu5Gc on sperm CD52 triggers anti-Neu5Gc antibody response in CMAH-deficient females, reducing fertility.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "BBB dysfunction", "glycan_involvement": "Neu5Gc-modified glycoproteins at BBB are immunogenic.", "mechanism": "Neu5Gc incorporation creates targets for anti-Neu5Gc antibodies, increasing BBB permeability.", "protein": "Sialylated glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11806805" }, { "confidence": "high", "disease": "Muscular dystrophy (Duchenne, Becker, Limb-Girdle, Walker\u2013Warburg syndrome)", "glycan_involvement": "O-glycosylation of mucin-like domain is essential for ligand binding.", "mechanism": "Defective glycosylation impairs ECM binding, leading to membrane instability and muscle degeneration.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "high", "disease": "Secondary dystroglycanopathies", "glycan_involvement": "O-glycosylation defects in mucin-like domain.", "mechanism": "Mutations in glycosyltransferases (FKRP, fukutin, LARGE, POMT1/2) cause hypoglycosylation, disrupting ECM interactions.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "high", "disease": "Schwartz-Jampel syndrome (SJS)", "glycan_involvement": "HS/CS glycosylation affects ECM binding and function.", "mechanism": "Mutations in perlecan gene or domain V impair ECM structure, causing skeletal abnormalities.", "protein": "Perlecan", "protein_enriched": { "function": "Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is b", "gene_name": "HSPG2", "glycan_count": 183, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G43417UB", "G57321FI", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G08918WF", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G14972EH", "G20706XG", "G23719VF", "G27058EU", "G27126ED", "G34989PA", "G35029YA", "G36379GD", "G37412TK", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44437FL", "G45395BF", "G45504EY", "G46691LC", "G47702MW", "G49955PK", "G57776ZU", "G59626AS", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G77669RF", "G80920RR", "G83633GK", "G86182NS", "G87661QW", "G90382BL", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G95177YH", "G95865ZB", "G29068FM", "G58001LT", "G73004SD", "G40740AD", "G57317CE", "G53434XO", "G00273SJ", "G01650EU", "G02528FI", "G03382KH", "G04854VP", "G09197ZW", "G10773YW", "G10846ZT", "G11870QZ", "G12341GU", "G14994KB", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G23505EP", "G23863VK", "G23984SE", "G25418HZ", "G25451PN", "G28541PG", "G28681TP", "G29184RN", "G29299MO", "G31028YV", "G31852PQ", "G35253PZ", "G37399XV", "G37509XX", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41840AI", "G44215PV", "G46503DX", "G46687AB", "G46902YN", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51640FO", "G59924QI", "G63041LO", "G65092SV", "G68490OW", "G73430PD", "G73968GN", "G75983OB", "G77547TA", "G79666IR", "G80223IX", "G82463GQ", "G82830MN", "G83646BJ", "G84349RE", "G84452RH", "G84820NF", "G85554PZ", "G87389XI", "G88891KO", "G92062TF", "G96091TT", "G98611JV", "G99679NM", "G01485JJ", "G22572EH", "G27947YN", "G37995HC", "G43669FQ", "G43734MM", "G57776ZS", "G60033FS", "G60834IK", "G75418YA", "G80075MS", "G84862VB", "G86880BF", "G87123QX", "G89045VA", "G91636VS", "G94470IW", "G49108TO", "G22310AV", "G83229XP", "G81006GJ", "G29931IJ", "G02628JF", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G20425TQ", "G23432EQ", "G25079LO", "G26330YA", "G31986NC", "G33609NS", "G37818NZ", "G39188ZX", "G43769HG", "G49906RN", "G52527GH", "G55383ZG", "G64527OM", "G69521XL", "G70223PD", "G72291OX", "G72398FA", "G78790NZ", "G83460ZZ", "G84225JN", "G86795LJ", "G89098OM", "G99668VU" ], "uniprot_id": "P98160" }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "high", "disease": "Silverman-Handmaker dyssegmental dysplasia (DDSH)", "glycan_involvement": "Loss of glycosylated perlecan disrupts ECM integrity.", "mechanism": "Absence of perlecan leads to severe chondrodysplasia and myotonia.", "protein": "Perlecan", "protein_enriched": { "function": "Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is b", "gene_name": "HSPG2", "glycan_count": 183, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G43417UB", "G57321FI", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G08918WF", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G14972EH", "G20706XG", "G23719VF", "G27058EU", "G27126ED", "G34989PA", "G35029YA", "G36379GD", "G37412TK", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44437FL", "G45395BF", "G45504EY", "G46691LC", "G47702MW", "G49955PK", "G57776ZU", "G59626AS", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G77669RF", "G80920RR", "G83633GK", "G86182NS", "G87661QW", "G90382BL", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G95177YH", "G95865ZB", "G29068FM", "G58001LT", "G73004SD", "G40740AD", "G57317CE", "G53434XO", "G00273SJ", "G01650EU", "G02528FI", "G03382KH", "G04854VP", "G09197ZW", "G10773YW", "G10846ZT", "G11870QZ", "G12341GU", "G14994KB", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G23505EP", "G23863VK", "G23984SE", "G25418HZ", "G25451PN", "G28541PG", "G28681TP", "G29184RN", "G29299MO", "G31028YV", "G31852PQ", "G35253PZ", "G37399XV", "G37509XX", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41840AI", "G44215PV", "G46503DX", "G46687AB", "G46902YN", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51640FO", "G59924QI", "G63041LO", "G65092SV", "G68490OW", "G73430PD", "G73968GN", "G75983OB", "G77547TA", "G79666IR", "G80223IX", "G82463GQ", "G82830MN", "G83646BJ", "G84349RE", "G84452RH", "G84820NF", "G85554PZ", "G87389XI", "G88891KO", "G92062TF", "G96091TT", "G98611JV", "G99679NM", "G01485JJ", "G22572EH", "G27947YN", "G37995HC", "G43669FQ", "G43734MM", "G57776ZS", "G60033FS", "G60834IK", "G75418YA", "G80075MS", "G84862VB", "G86880BF", "G87123QX", "G89045VA", "G91636VS", "G94470IW", "G49108TO", "G22310AV", "G83229XP", "G81006GJ", "G29931IJ", "G02628JF", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G20425TQ", "G23432EQ", "G25079LO", "G26330YA", "G31986NC", "G33609NS", "G37818NZ", "G39188ZX", "G43769HG", "G49906RN", "G52527GH", "G55383ZG", "G64527OM", "G69521XL", "G70223PD", "G72291OX", "G72398FA", "G78790NZ", "G83460ZZ", "G84225JN", "G86795LJ", "G89098OM", "G99668VU" ], "uniprot_id": "P98160" }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "medium", "disease": "Poor bone mineral density/fracture risk", "glycan_involvement": "Glycosylation required for ECM ligand binding in bone.", "mechanism": "Defective DGC function in bone cells impairs bone modeling/remodeling, independent of muscle loading.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "high", "disease": "Short stature", "glycan_involvement": "Heparan sulfate glycosylation mediates ECM interactions.", "mechanism": "Agrin deficiency impairs chondrocyte proliferation and cartilage matrix deposition, reducing longitudinal growth.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "medium", "disease": "Cartilage degeneration/Osteoarthritis", "glycan_involvement": "Glycosylation of laminin chains affects ECM stability.", "mechanism": "Reduced laminin expression in cartilage correlates with degeneration and aging.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "medium", "disease": "Osteomalacia/Osteoporosis/Osteopenia", "glycan_involvement": "Glycosylation of \u03b1-dystroglycan required for ligand binding.", "mechanism": "Defective DGC-ECM interactions in bone cells lead to impaired bone formation and increased resorption.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "O-glucosylation of Notch domains and \u03b1-dystroglycan.", "mechanism": "POGLUT1 mutations cause \u03b1-dystroglycan hypoglycosylation and aberrant Notch signaling, leading to muscle disease.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "medium", "disease": "Alagille syndrome/Spondylocostal dysostosis", "glycan_involvement": "Glycosylation of dystroglycan required for proper Notch pathway function.", "mechanism": "Disrupted Notch signaling (with dystroglycan as downstream effector) leads to skeletal malformations.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC11807010" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "ALP elevation indicates cholestatic liver injury due to drug toxicity.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807716" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion and half-life.", "mechanism": "ALT elevation reflects hepatocellular injury from drug toxicity.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807716" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "AST is glycosylated; glycosylation may influence serum detection.", "mechanism": "AST elevation is a marker of hepatocellular injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807716" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation modulates ALP isoform distribution in serum.", "mechanism": "ALP is elevated in cholestatic liver disease.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807716" }, { "confidence": "medium", "disease": "Ampullary stenosis", "glycan_involvement": "Glycosylation affects ALP's serum half-life and diagnostic utility.", "mechanism": "ALP elevation reflects biliary obstruction due to ampullary stenosis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807716" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Altered glycosylation patterns of Reelin observed in AD brains; A\u03b2 affects Reelin glycosylation.", "mechanism": "Reduced Reelin function is involved in AD pathogenesis and progression; gain-of-function Reelin mutation (H3447R) is protective against cognitive decline despite amyloid accumulation.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "Reelin is glycosylated; altered glycosylation may affect function, but details unclear.", "mechanism": "Diminished Reelin expression/function correlates with onset and severity of schizophrenia symptoms.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11808024" }, { "confidence": "medium", "disease": "Autism spectrum disorders", "glycan_involvement": "Reelin glycosylation status not directly linked to ASD, but overall glycosylation may modulate function.", "mechanism": "Reduced RELN mRNA and protein levels in ASD; increased promoter methylation suppresses expression.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Pachygyria", "glycan_involvement": "Not specified.", "mechanism": "Mutations in Reelin (e.g., Y1821H, G1280E, R913C) cause abnormal brain development (pachygyria); some mutations show gain-of-function.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC11808024" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Not specified.", "mechanism": "Reduced or lost Reelin function may be advantageous in non-neuronal cardiovascular diseases.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "protective", "source_pmcid": "PMC11808024" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Not specified.", "mechanism": "Reduced Reelin function may be beneficial in inflammatory diseases.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "protective", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "APP is a glycoprotein; glycosylation may affect processing.", "mechanism": "APP is cleaved to produce A\u03b2; Reelin interacts with APP and inhibits its ectodomain shedding, potentially modulating A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Direct evidence of altered glycosylation in AD.", "mechanism": "Altered Reelin glycosylation and decreased non-ConA-binding Reelin in AD frontal cortex.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "biomarker", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation may affect secretion and function.", "mechanism": "Enhancing Reelin function (e.g., via protease inhibition or gain-of-function mutations) may ameliorate AD symptoms.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "Not specified.", "mechanism": "Reduced RELN mRNA and protein levels in patient brains.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "biomarker", "source_pmcid": "PMC11808024" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation (CDG-I pattern)", "mechanism": "Transferrin shows loss of N-glycans due to impaired mannose donor synthesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11808201" }, { "confidence": "high", "disease": "ALG9-CDG", "glycan_involvement": "Defective N-glycosylation (CDG-I pattern)", "mechanism": "Transferrin lacks N-glycans due to defective glycan precursor synthesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11808201" }, { "confidence": "high", "disease": "COG-CDG", "glycan_involvement": "Abnormal N-glycan processing (CDG-II pattern)", "mechanism": "Transferrin shows loss of terminal sialic acid and galactose due to Golgi trafficking defects.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11808201" }, { "confidence": "high", "disease": "FUT8-CDG", "glycan_involvement": "Defective N-glycan core fucosylation", "mechanism": "Loss of core fucosylation on transferrin due to FUT8 deficiency.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09263" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "Cutaneous Squamous Cell Carcinoma (CSCC)", "glycan_involvement": "Glycosylation modulates PD-L1 stability and immune recognition.", "mechanism": "PD-L1 inhibition restores anti-tumor T cell responses.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "Colorectal Cancer (MSSCRC)", "glycan_involvement": "Glycosylation affects PD-1 receptor-ligand interactions.", "mechanism": "PD-1 blockade enhances anti-tumor immunity.", "protein": "PD-1 (PDCD1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "Colorectal Cancer (MSSCRC)", "glycan_involvement": "Glycosylation influences CTLA-4 cell surface expression.", "mechanism": "CTLA-4 inhibition promotes T cell activation against tumor.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation regulates PD-L1 immune evasion.", "mechanism": "PD-L1 blockade in combination therapy improves response rates.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation required for VEGF receptor binding.", "mechanism": "VEGF inhibition reduces tumor angiogenesis.", "protein": "VEGF (VEGFA)", "protein_enriched": { "function": "Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (PubMed:35455969). Involved in protecting cells from hypoxia-mediated ", "gene_name": "VEGFA", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G82348BZ" ], "uniprot_id": "P15692" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "IL-27 inhibition modulates tumor immune microenvironment.", "protein": "IL-27", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NUZ8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "medium", "disease": "Type 1 Diabetes", "glycan_involvement": "Fc glycosylation modulates effector function and half-life.", "mechanism": "Polyclonal IgG targets T cells to delay beta cell destruction.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "medium", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation influences CD3 complex stability and signaling.", "mechanism": "CD3 inhibition induces Tregs and reduces inflammation.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "low", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation impacts CD3-mediated T cell activation.", "mechanism": "CD3 inhibitor under investigation for immune modulation.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11812393" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are diagnostic markers for antiphospholipid syndrome.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "medium", "disease": "ischemic colitis", "glycan_involvement": "Glycosylation required for secretion and anticoagulant activity.", "mechanism": "Deficiency can predispose to thrombotic events leading to ischemic colitis.", "protein": "antithrombin", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "medium", "disease": "ischemic colitis", "glycan_involvement": "N-glycosylation essential for protein C function.", "mechanism": "Deficiency can increase risk of thrombosis and ischemic colitis.", "protein": "protein C", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "medium", "disease": "ischemic colitis", "glycan_involvement": "Glycosylation modulates anticoagulant activity.", "mechanism": "Deficiency may predispose to thrombotic complications including ischemic colitis.", "protein": "protein S", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "medium", "disease": "ischemic colitis", "glycan_involvement": "Glycosylation affects stability and function.", "mechanism": "Factor V Leiden mutation increases risk of thrombosis and ischemic colitis.", "protein": "factor V", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "medium", "disease": "ischemic colitis", "glycan_involvement": "Glycosylation influences immune recognition.", "mechanism": "Anti-beta-2 glycoprotein I antibodies can indicate risk for vascular events including ischemic colitis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11814850" }, { "confidence": "high", "disease": "C1GALT1C1-CDG (COSMC-CDG)", "glycan_involvement": "Failure to generate Core 1 O-glycan; accumulation of Tn-antigen.", "mechanism": "Loss-of-function mutations in Cosmc impair T-synthase folding, leading to defective O-glycosylation.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "high", "disease": "C1GALT1C1-CDG (COSMC-CDG)", "glycan_involvement": "Reduced Core 1 O-glycan; increased Tn-antigen.", "mechanism": "Inactive T-synthase due to lack of Cosmc chaperoning results in abnormal glycoprotein O-glycosylation.", "protein": "T-synthase (C1GALT1)", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "high", "disease": "C1GALT1C1-CDG (COSMC-CDG)", "glycan_involvement": "Altered O-glycosylation profile.", "mechanism": "Reduced normal O-glycans and increased Tn-antigen detected in patient serum.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11826066" }, { "confidence": "high", "disease": "Tn syndrome", "glycan_involvement": "Aberrant O-glycosylation (Tn-antigen) on RBC surface.", "mechanism": "Somatic mutations in C1GALT1C1 in hematopoietic precursors cause Tn-antigen expression on RBCs.", "protein": "RBC glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "high", "disease": "Tn syndrome", "glycan_involvement": "Unmodified GalNAc\u03b11-Ser/Thr due to defective O-glycosylation.", "mechanism": "Presence of Tn-antigen on blood cells is diagnostic for Tn syndrome.", "protein": "Tn-antigen (CD175)", "relationship_type": "biomarker", "source_pmcid": "PMC11826066" }, { "confidence": "medium", "disease": "Nonimmune hydrops fetalis", "glycan_involvement": "Defective O-glycosylation in fetal tissues.", "mechanism": "Mosaic loss-of-function in Cosmc during development implicated in hydrops fetalis.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "medium", "disease": "Developmental delay", "glycan_involvement": "Reduced Core 1 O-glycan in neural glycoproteins.", "mechanism": "Impaired O-glycosylation affects neurodevelopment.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "medium", "disease": "Short stature", "glycan_involvement": "Abnormal O-glycosylation of growth-related glycoproteins.", "mechanism": "Defective glycosylation impacts growth factor signaling.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Altered glycoprotein O-glycans on leukocytes.", "mechanism": "Aberrant O-glycosylation impairs immune cell function.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Reduced Core 1 O-glycan on platelet surface proteins.", "mechanism": "Defective O-glycosylation affects platelet glycoproteins.", "protein": "Cosmc", "relationship_type": "causal", "source_pmcid": "PMC11826066" }, { "confidence": "high", "disease": "CADASIL", "glycan_involvement": "Altered O-fucose and Fringe-mediated glycosylation at EGF-like repeats modulates NOTCH3 turnover and function; mutations reduce glycosylation and increase aggregation.", "mechanism": "Missense mutations (often cysteine-altering) in NOTCH3 disrupt O-glycosylation, leading to protein aggregation and impaired signaling in vascular cells.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "O-GalNAc modification at linker regions is essential for LDLR stability and function; mutations reduce glycosylation, impairing LDL uptake.", "mechanism": "Missense mutations in LDLR, especially near glycosylation sites, impair O-GalNAc modification, reducing LDL binding and receptor stability.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "high", "disease": "Familial Alzheimer\u2019s Disease", "glycan_involvement": "N- and O-glycosylation regulate APP folding, trafficking, and cleavage; altered glycosylation in mutants increases A\u03b2 release.", "mechanism": "Pathogenic APP mutations (e.g., Swedish, London) alter glycosylation patterns, affecting A\u03b2 production and aggregation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "Familial Alzheimer\u2019s Disease", "glycan_involvement": "GnT-III-mediated bisecting GlcNAc on N-glycans of APP/BACE1 is protective against A\u03b2 production.", "mechanism": "Increased bisecting GlcNAc on APP and BACE1 reduces A\u03b2 secretion.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "protective", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "Familial Alzheimer\u2019s Disease", "glycan_involvement": "O-GalNAc modification at specific tyrosine synergizes with mutation to increase pathogenic cleavage.", "mechanism": "O-GalNAcylation at tyrosine (Y681 in APP770) increases \u03b2-cleavage of Swedish mutant, enhancing A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "RFNG-mediated O-fucose elongation is reduced in mutants, further impairing NOTCH3 function under aging conditions.", "mechanism": "Aging and increased RFNG expression exacerbate signaling defects and protein accumulation in NOTCH3 mutants.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "Defective N- and O-glycosylation leads to ER retention and loss of function.", "mechanism": "Class 2 LDLR mutations cause glycosylation-immature forms retained in ER, reducing cell surface expression.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "Familial Alzheimer\u2019s Disease", "glycan_involvement": "O-GalNAc and O-GlcNAc modifications are required for proper APP trafficking and processing.", "mechanism": "O-Glycan-deficient APP mutants are retained in ER, impairing processing and increasing pathogenic potential.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "Disrupted glycosylation consensus sequences reduce O-GalNAc modification and LDL binding.", "mechanism": "Cysteine-sparing mutations may cause abnormal disulfide bonds and reduced glycosylation, impairing LDLR function.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "medium", "disease": "Familial Alzheimer\u2019s Disease", "glycan_involvement": "ST6Gal-I-mediated sialylation of N-glycans increases amyloidogenic processing.", "mechanism": "Enhanced sialylation of APP N-glycans increases A\u03b2 release, especially in Swedish mutant.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11832388" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects APP processing.", "mechanism": "Extracellular accumulation forms amyloid plaques, driving neurodegeneration.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Peripheral A\u03b2 derived from glycosylated APP; glycosylation modulates secretion and aggregation.", "mechanism": "A\u03b2 accumulates in myocardium, causing cardiac amyloidosis and dysfunction.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP glycosylation influences secretase cleavage and A\u03b2 generation.", "mechanism": "Abnormal APP processing via \u03b2/\u03b3-secretases increases A\u03b2 production.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation may affect PSN-1 stability and function.", "mechanism": "PSN-1 mutations increase APP cleavage, A\u03b2 aggregation.", "protein": "Presenilin-1 (PSN-1)", "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Idiopathic dilated cardiomyopathy", "glycan_involvement": "Glycosylation may modulate PSN-1 cardiac effects.", "mechanism": "PSN-1 mutations linked to cardiac dysfunction and dilated cardiomyopathy.", "protein": "Presenilin-1 (PSN-1)", "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Tau glycosylation affects aggregation and tangle formation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, driving neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Heart failure (HF)", "glycan_involvement": "LPR-1 glycosylation required for receptor function.", "mechanism": "LPR-1 mediates A\u03b2 efflux from myocardium, reducing cardiac injury.", "protein": "Low-density lipoprotein receptor-related protein 1 (LPR-1)", "protein_enriched": { "function": "Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657). Required for early embryonic development (By similarity). Involved in cellular lip", "gene_name": "LRP1", "glycan_count": 176, "glycosylation_sites_count": 52, "glytoucan_ids": [ "G43417UB", "G62765YT", "G29068FM", "G57321FI", "G02815KT", "G07246CJ", "G23719VF", "G25079LO", "G27058EU", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G70441OD", "G73291XG", "G79666IR", "G80920RR", "G90659AW", "G96091TT", "G04657PL", "G11629QQ", "G14972EH", "G20706XG", "G46691LC", "G77669RF", "G80075MS", "G84452RH", "G87123QX", "G95177YH", "G01650EU", "G05049YU", "G10486CT", "G10488MI", "G11314AS", "G18647XP", "G22310AV", "G23294PN", "G23863VK", "G25418HZ", "G25451PN", "G28541PG", "G33791AF", "G37881RL", "G39446WN", "G47644PP", "G49955PK", "G52527GH", "G57776ZU", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G63041LO", "G65184UU", "G66621EA", "G70619PT", "G72790NZ", "G75983OB", "G80223IX", "G80479JV", "G82830MN", "G83460ZZ", "G85269DF", "G87661QW", "G27126ED", "G02886BB", "G05724UK", "G08918WF", "G11870QZ", "G12313PD", "G20210JR", "G29184RN", "G37399XV", "G39619TI", "G41840AI", "G46503DX", "G48584BU", "G51640FO", "G64527OM", "G70101JE", "G72747WU", "G81263BG", "G83646BJ", "G92406TI", "G95865ZB", "G06110VR", "G98208DX", "G01485JJ", "G34029GR", "G44215PV", "G46902YN", "G47950XN", "G50045TK", "G61256FT", "G72398FA", "G72787SB", "G83633GK", "G92551JA", "G71142DF", "G08290VR", "G39188ZX", "G72291OX", "G02030ZB", "G06356OH", "G38663NM", "G45504EY", "G48414YA", "G57888GL", "G59536GA", "G92050GC", "G55412XP", "G09197ZW", "G10819WX", "G62595EF", "G93656SY", "G13694XX", "G43089EG", "G47012YE", "G47748JZ", "G57776ZS", "G62461SM", "G15664MX", "G17208MA", "G29299MO", "G35253PZ", "G76295SF", "G00912UN", "G10846ZT", "G40574BA", "G40926MX", "G49018RC", "G49906RN", "G02528FI", "G24528MX", "G43669FQ", "G78787DI", "G68490OW", "G40834TG", "G93718GY", "G49108TO", "G90382BL", "G27915IV", "G32788FZ", "G35541EV", "G59324HL", "G70232NH", "G84349RE", "G89827JR", "G00273SJ", "G07755XJ", "G23984SE", "G36379GD", "G57317CE", "G66163OV", "G83229XP", "G20579QQ", "G28681TP", "G77547TA", "G92135MA", "G24954UD", "G72797UR", "G82119TF", "G56784JY", "G60967DT", "G66766XF", "G72735IY", "G31433PN", "G31685JQ", "G43769HG", "G86234IN", "G96430BV", "G39595FH", "G58802FE", "G64394MX" ], "uniprot_id": "Q07954" }, "relationship_type": "protective", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Heart failure (HF)", "glycan_involvement": "RAGE is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "RAGE upregulation enhances A\u03b2 accumulation in myocardium, promoting HF.", "protein": "Receptor for advanced glycation end products (RAGE)", "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "NEP glycosylation affects enzyme stability and activity.", "mechanism": "NEP degrades A\u03b2; reduced NEP activity increases A\u03b2 accumulation.", "protein": "Neprilysin (NEP)", "protein_enriched": { "function": "Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:6208535, PubMed:6349683, PubMed:8168535). Biologically important in the ", "gene_name": "MME", "glycan_count": 93, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G07246CJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G20528HD", "G24528MX", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G28681TP", "G30970QQ", "G31852PQ", "G35029YA", "G37509XX", "G37818NZ", "G37995HC", "G40926MX", "G41071NU", "G42124LM", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G49906RN", "G49955PK", "G50045TK", "G57317CE", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G65184UU", "G68490OW", "G70223PD", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G73968GN", "G76295SF", "G80479JV", "G80920RR", "G83460ZZ", "G83633GK", "G83646BJ", "G84225JN", "G85282JO", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G00273SJ", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G11115RO", "G13131HA", "G13191RB", "G14972EH", "G16125XL", "G27947YN", "G28622IK", "G29545VG", "G35541EV", "G39471UU", "G43223CG", "G45395BF", "G49755GI", "G53075ES", "G55132BD", "G58087IP", "G60834IK", "G69521XL", "G77547TA", "G79666IR", "G80075MS", "G81637OR", "G86880BF", "G92135MA", "G92275SC", "G93718GY", "G98611JV", "G99679NM" ], "uniprot_id": "P08473" }, "relationship_type": "protective", "source_pmcid": "PMC11832649" }, { "confidence": "medium", "disease": "Heart failure (HF)", "glycan_involvement": "TTR glycosylation may affect aggregation propensity.", "mechanism": "Misfolded TTR aggregates contribute to cardiac amyloidosis and HF.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "causal", "source_pmcid": "PMC11832649" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects APP processing and A\u03b2 aggregation.", "mechanism": "A\u03b2 plaque deposition in neural tissue is a hallmark of AD pathogenesis and is detectable by PET imaging; early accumulation predicts progression from MCI to AD.", "protein": "Beta-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates tau aggregation and pathology.", "mechanism": "Phosphorylated tau forms neurofibrillary tangles; tau PET signal predicts future neurodegeneration and brain atrophy.", "protein": "Tau protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation regulates APP trafficking and cleavage.", "mechanism": "Mutations in APP gene cause early-onset familial AD; APP glycosylation influences A\u03b2 production.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APOE is N-glycosylated; glycosylation affects lipid binding and A\u03b2 interaction.", "mechanism": "APOE alleles (especially \u03b54) increase risk for AD; APOE modulates A\u03b2 clearance and aggregation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11841692" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Presenilin 1 is glycosylated; glycosylation may affect \u03b3-secretase complex assembly.", "mechanism": "Mutations in presenilin 1 gene cause familial AD by altering \u03b3-secretase activity and A\u03b2 production.", "protein": "Presenilin 1", "relationship_type": "causal", "source_pmcid": "PMC11841692" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Presenilin 2 is glycosylated; glycosylation may influence protein stability.", "mechanism": "Mutations in presenilin 2 gene cause familial AD via altered \u03b3-secretase activity.", "protein": "Presenilin 2", "relationship_type": "causal", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Derived from glycosylated APP; glycosylation status influences A\u03b2 aggregation.", "mechanism": "A\u03b2 PET positivity in MCI predicts progression to AD and cognitive decline.", "protein": "Beta-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "O-glycosylation modulates tau aggregation propensity.", "mechanism": "Tau PET signal in MCI predicts future neurodegeneration and conversion to AD.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11841692" }, { "confidence": "medium", "disease": "Frontotemporal lobar degeneration (FTLD)", "glycan_involvement": "Tau glycosylation may differ between AD and FTLD, affecting aggregation.", "mechanism": "Tau PET imaging differentiates AD from FTLD based on regional tau deposition patterns.", "protein": "Tau protein", "relationship_type": "biomarker/differential diagnosis", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "A\u03b2 aggregation influenced by glycosylation of precursor APP.", "mechanism": "A\u03b2 PET positivity distinguishes AD-related dementia from other causes.", "protein": "Beta-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11841692" }, { "confidence": "high", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Altered N-glycosylation patterns (up/down-regulation of specific glycopeptides) are associated with disease presence and progression.", "mechanism": "Differential expression of 12 intact N-glycopeptides in plasma IgG distinguishes SSc patients from healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "high", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Elevated sialylated N-glycans (e.g., IgG2-N3H6F1A1, IgG2-N4H4F1A1) in SSc plasma.", "mechanism": "Increased IgG sialylation in SSc patients may be linked to immune modulation and tumor susceptibility.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Specific N-glycopeptide downregulation may reflect lung involvement and fibrosis.", "mechanism": "Decreased levels of IgG2-N4H4F1 and IgG2-N4H4F1A1 are negatively correlated with ILD in SSc patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Cardiovascular involvement in SSc", "glycan_involvement": "Distinct N-glycopeptide expression patterns linked to organ-specific damage.", "mechanism": "IgG2-N4H3F1 (up) and IgG2-N4H5F1 (down) correlate with cardiovascular complications in SSc.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "N-glycosylation pattern reflects disease severity/subtype.", "mechanism": "IgG2-N4H4 positively correlates with diffuse SSc subtype.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Progressive changes in N-glycosylation with disease course.", "mechanism": "IgG2-N3H6F1A1, IgG2-N4H4, and IgG2-N4H4F1A1 positively correlate with disease duration.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "N-glycosylation may influence autoantibody profiles.", "mechanism": "IgG2-N3H3F1 and IgG2-N4H3F1 positively correlate with anti-Scl-70 antibody status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "Altered N-glycosylation may modulate autoantibody production.", "mechanism": "IgG2-N4H5F1, IgG2-N5H4F1, and IgG2-N5H5F1 negatively correlate with anti-Scl-70 antibody status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "medium", "disease": "Systemic sclerosis (SSc)", "glycan_involvement": "N-glycosylation changes reflect systemic inflammation.", "mechanism": "IgG2-N4H5F1, IgG2-N5H4F1, and IgG2-N5H5F1 negatively correlate with C-reactive protein (CRP), an inflammation marker.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842340" }, { "confidence": "low", "disease": "Lung cancer (in SSc context)", "glycan_involvement": "Upregulated sialylated N-glycans inhibit T-cell activity, facilitating tumor development.", "mechanism": "Elevated IgG sialylation in SSc may contribute to increased lung cancer risk via immune escape.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (risk association)", "source_pmcid": "PMC11842340" }, { "confidence": "high", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Targeted by vaccines to block viral attachment and entry.", "protein": "HRSV G glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "Glycosylation affects fusion activity and immunogenicity.", "mechanism": "Targeted by vaccines to inhibit fusion and viral entry.", "protein": "HRSV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield masks epitopes from antibodies.", "mechanism": "Env glycoprotein shields neutralizing epitopes, targeted in vaccine design.", "protein": "HIV envelope glycoprotein (Env)", "relationship_type": "immune_evasion/therapeutic_target", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation modulates antigenicity and immune escape.", "mechanism": "Envelope glycoproteins induce immune response; targeted in vaccine candidates.", "protein": "Hepatitis C envelope glycoproteins (E1/E2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Cervical cancer (HPV)", "glycan_involvement": "Glycosylation influences VLP assembly and immunogenicity.", "mechanism": "L1 protein forms virus-like particles, used in vaccines to prevent HPV infection.", "protein": "HPV L1 glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "medium", "disease": "Cervical cancer (HPV)", "glycan_involvement": "Glycosylation may affect antigen presentation.", "mechanism": "L2 protein involved in viral entry, targeted in some vaccine designs.", "protein": "HPV L2 glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune recognition.", "mechanism": "HA is the main antigen in influenza vaccines, mediates viral entry.", "protein": "Influenza hemagglutinin (HA)", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and immune response.", "mechanism": "NA is targeted by vaccines and antivirals to block viral release.", "protein": "Influenza neuraminidase (NA)", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation influences immunogenicity.", "mechanism": "G protein is the main antigen in rabies vaccines, induces neutralizing antibodies.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation forms a shield, modulates immune recognition.", "mechanism": "Spike protein is the main antigen in COVID-19 vaccines, mediates viral entry.", "protein": "SARS-CoV-2 spike glycoprotein (S)", "relationship_type": "protective", "source_pmcid": "PMC11842373" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "N-glycosylation is essential for LRG stability and secretion; glycosylation may affect its detection and function as a biomarker.", "mechanism": "LRG is produced by neutrophils, macrophages, and intestinal epithelial cells under inflammatory conditions; serum levels correlate with endoscopic activity and mucosal inflammation.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843037" }, { "confidence": "high", "disease": "Ileitis", "glycan_involvement": "N-glycosylation supports LRG's plasma stability and detection.", "mechanism": "LRG levels are elevated in active ileal lesions and correlate strongly with endoscopic activity in the ileum.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843037" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "N-glycosylation supports LRG's plasma stability and detection.", "mechanism": "LRG levels are elevated in active colonic lesions and correlate with endoscopic activity in the colon.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", 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"G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843037" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation affects CRP's solubility and immune recognition.", "mechanism": "CRP is an acute-phase reactant used to assess inflammation, but has lower sensitivity for small bowel lesions compared to LRG.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11843037" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "N-glycosylation is required for LRG's secretion and function.", "mechanism": "LRG is superior to CRP in detecting small bowel lesions and endoscopic healing in Crohn's disease.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", 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Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). 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"G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", 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May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "high", "disease": "Alagille syndrome", "glycan_involvement": "NOTCH2 is glycosylated; glycosylation modulates receptor function and signaling.", "mechanism": "NOTCH2 mutations also disrupt Notch pathway, leading to similar phenotypes as JAG1 mutations.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation of JAG1 may influence its stability and signaling capacity.", "mechanism": "JAG1 mutation leads to intrahepatic bile duct paucity, causing chronic cholestasis.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation may affect JAG1 function in hepatic tissue.", "mechanism": "Impaired bile duct development disrupts cholesterol excretion, causing severe hypercholesterolemia.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "LDL contains glycoprotein apolipoprotein B; glycosylation affects LDL clearance.", "mechanism": "Elevated LDL is a marker of impaired cholesterol metabolism in Alagille syndrome.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11843072" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "GGT is glycosylated; glycosylation affects enzyme stability and secretion.", "mechanism": "Elevated GGT reflects cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843072" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "ALP glycosylation modulates enzyme activity and tissue distribution.", "mechanism": "Elevated ALP is indicative of bile duct injury or obstruction.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843072" }, { "confidence": "medium", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation may influence JAG1 function in heart tissue.", "mechanism": "JAG1 mutation affects Notch signaling in cardiac development, leading to defects.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "medium", "disease": "Infantile hepatitis syndrome", "glycan_involvement": "Glycosylation may affect JAG1 stability and hepatic signaling.", "mechanism": "JAG1 mutation can present as infantile hepatitis due to bile duct paucity.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "medium", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation modulates NOTCH2 receptor-ligand interactions.", "mechanism": "NOTCH2 mutation disrupts cardiac development via Notch pathway.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal", "source_pmcid": "PMC11843072" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Heavily glycosylated when secreted; glycosylation may affect secretion and function.", "mechanism": "Antioxidant, anti-inflammatory, and antiapoptotic activities; inhibits PAPP-A, reducing IGF activity and glomerular hypertrophy.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Secreted STC-1 is heavily glycosylated, possibly influencing stability and activity.", "mechanism": "STC-1 levels increase in CKD; provides renoprotection via antioxidant and anti-inflammatory effects.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11843109" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation status may affect secretion and receptor interaction.", "mechanism": "Reduces calcium overload, inhibits inflammation and apoptosis in myocardium, improves cardiac function after ischemia-reperfusion.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "high", "disease": "Ischemia-reperfusion injury", "glycan_involvement": "Secreted, glycosylated form is active in protection.", "mechanism": "Activates AMPK pathway, upregulates UCP2 and SIRT3, reduces oxidative stress and apoptosis.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "medium", "disease": "Nephrotoxic nephritis", "glycan_involvement": "No direct evidence, but secreted glycosylated form likely mediates effect.", "mechanism": "Inhibits macrophage infiltration, stabilizes endothelial barrier, reduces inflammation.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect circulating levels and activity.", "mechanism": "Upregulated in failing myocardium; reduces calcium influx in cardiomyocytes.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11843109" }, { "confidence": "high", "disease": "Contrast-induced acute kidney injury (CI-AKI)", "glycan_involvement": "Active as secreted glycosylated protein.", "mechanism": "Regulates mitochondrial quality control, suppresses oxidative stress and apoptosis in renal tubular cells.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect hormone stability and function.", "mechanism": "Antihypercalcemic effect reduces vascular calcification and progression of atherosclerosis.", "protein": "Stanniocalcin-1 (STC-1)", "protein_enriched": { "function": "May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE)", "gene_name": "CUTA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G58001LT" ], "uniprot_id": "O60888" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Not specified, but as a glycoprotein, glycosylation may modulate activity.", "mechanism": "Inhibits PAPP-A, reducing IGF activity and glomerular hypertrophy.", "protein": "Stanniocalcin-2 (STC-2)", "protein_enriched": { "function": "Mitochondrial iron transporter that specifically mediates iron uptake in developing erythroid cells, thereby playing an essential role in heme biosynthesis", "gene_name": "SLC25A37", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NYZ2" }, "relationship_type": "protective", "source_pmcid": "PMC11843109" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "PAPP-A is a glycoprotein; glycosylation may affect its activity.", "mechanism": "Increased PAPP-A activity promotes IGF signaling, leading to glomerular hypertrophy.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "causal", "source_pmcid": "PMC11843109" }, { "confidence": "high", "disease": "von Willebrand disease (VWD)", "glycan_involvement": "VWF is a heavily glycosylated protein; glycosylation affects its multimerization and function.", "mechanism": "Defects in VWF synthesis, structure, secretion, or function cause VWD.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease type 2M", "glycan_involvement": "Glycosylation of VWF modulates its interaction with GP1b; mutations may affect glycan-mediated binding.", "mechanism": "Type 2M VWD is caused by VWF variants with defective binding to platelet GP1b, impairing platelet adhesion.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may influence VWF's interaction with platelets and immune system, possibly affecting platelet consumption.", "mechanism": "Administration of VWF/FVIII concentrate (wilate) temporally associated with severe post-surgical thrombocytopenia.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal/therapeutic complication", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease (VWD)", "glycan_involvement": "FVIII glycosylation affects its stability and interaction with VWF.", "mechanism": "FVIII levels are reduced in VWD due to lack of VWF carrier function; FVIII/VWF concentrates used for treatment.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease type 2M", "glycan_involvement": "GP1b is glycosylated; glycan structures modulate VWF-GP1b interaction.", "mechanism": "Mutations in VWF A1 domain impair binding to GP1b, leading to defective platelet adhesion in type 2M VWD.", "protein": "Glycoprotein 1b (GP1b)", "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation of VWF influences its affinity for platelets.", "mechanism": "Type 2B VWD causes thrombocytopenia via increased VWF-platelet interaction and aggregation.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal (other VWD subtypes)", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease type 2B", "glycan_involvement": "Altered glycosylation may enhance VWF-platelet binding.", "mechanism": "Type 2B VWD is characterized by increased ristocetin-induced platelet aggregation and thrombocytopenia.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease type 1", "glycan_involvement": "Glycosylation affects VWF secretion and plasma levels.", "mechanism": "Type 1 VWD is due to quantitative deficiency of VWF.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "von Willebrand disease type 3", "glycan_involvement": "Glycosylation defects may contribute to VWF absence.", "mechanism": "Type 3 VWD is due to near-complete absence of VWF.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11846128" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may affect immunogenicity and platelet interactions.", "mechanism": "Wilate administration may trigger platelet consumption post-surgery in VWD type 2M patient.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "therapeutic complication", "source_pmcid": "PMC11846128" }, { "confidence": "high", "disease": "Cardiovascular events (CVE)", "glycan_involvement": "N-acetylglucosamine/N-acetylgalactosamine acetyl groups detected by NMR; reflects glycosylation changes in acute-phase proteins.", "mechanism": "Elevated Glyc A reflects chronic inflammation, associated with increased CVE risk in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "high", "disease": "Cardiovascular events (CVE)", "glycan_involvement": "N-acetylneuraminic acid acetyl groups; indicates sialylation changes in glycoproteins.", "mechanism": "Elevated Glyc B is associated with increased CVE risk in T2D, reflecting inflammation.", "protein": "Glyc B", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Reflects increased glycosylation of acute-phase proteins in diabetes.", "mechanism": "Higher Glyc A levels are linked to incident T2D and chronic inflammation.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation changes in serum proteins detected by NMR.", "mechanism": "Glyc A is associated with subclinical atherosclerosis in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Reflects systemic inflammation via glycosylated acute-phase proteins.", "mechanism": "Elevated Glyc A improves prediction of stroke events in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation of serum proteins involved in inflammation.", "mechanism": "Higher Glyc A levels are predictive of heart failure risk in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Peripheral arterial disease", "glycan_involvement": "Reflects glycosylation changes in inflammatory proteins.", "mechanism": "Glyc A elevation is associated with increased risk of peripheral arterial disease in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Acute myocardial infarction", "glycan_involvement": "Acute-phase glycoprotein glycosylation detected by NMR.", "mechanism": "Glyc A improves prediction of myocardial infarction in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Angina pectoris", "glycan_involvement": "Reflects glycosylation changes in serum proteins.", "mechanism": "Elevated Glyc A is predictive of angina risk in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation of acute-phase proteins detected by NMR.", "mechanism": "Glyc A elevation is associated with increased risk of ischemic heart disease in T2D.", "protein": "Glyc A", "relationship_type": "biomarker", "source_pmcid": "PMC11846359" }, { "confidence": "high", "disease": "ALG12-CDG", "glycan_involvement": "Deficient N-glycan addition due to ALG12 loss-of-function leads to abnormal transferrin glycoforms.", "mechanism": "Hypoglycosylated transferrin isoforms detected in patient serum indicate defective N-glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "ALG12-CDG", "glycan_involvement": "Incomplete N-glycan addition due to ALG12 deficiency.", "mechanism": "Hypoglycosylated orosomucoid detected in patient serum reflects impaired N-glycosylation.", "protein": "Orosomucoid", "relationship_type": "biomarker", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "ALG12-CDG", "glycan_involvement": "Defective N-glycan processing from ALG12 mutation.", "mechanism": "Hypoglycosylated alpha-1-antitrypsin isoforms indicate N-glycosylation defects.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "ALG12-CDG", "glycan_involvement": "Incomplete N-glycan addition due to ALG12 loss-of-function.", "mechanism": "Hypoglycosylated haptoglobin isoforms reflect N-glycosylation impairment.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "ALG12-CDG", "glycan_involvement": "Defective N-glycan precursor assembly in ER leads to hypoglycosylation of multiple glycoproteins.", "mechanism": "Loss-of-function mutation in ALG12 impairs dolichyl-P-Man:Man7GlcNAc2-PP-dolichol alpha-6 mannosyltransferase activity, blocking N-glycan precursor synthesis.", "protein": "ALG12", "protein_enriched": { "function": "Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-link", "gene_name": "ALG12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9BV10" }, "relationship_type": "causal", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "RFT1-CDG", "glycan_involvement": "Defective N-glycan precursor assembly in ER.", "mechanism": "Pathogenic RFT1 mutations impair flipping of Man5GlcNAc2-PP-dolichol across ER membrane, blocking N-glycan precursor synthesis.", "protein": "RFT1", "protein_enriched": { "function": "Intramembrane glycolipid transporter that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The sequenti", "gene_name": "RFT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G58087IP", "G49108TO" ], "uniprot_id": "Q96AA3" }, "relationship_type": "causal", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "CDG-I", "glycan_involvement": "Impaired N-glycan precursor synthesis in ER.", "mechanism": "ALG12 mutations cause a subtype of CDG-I by disrupting early steps of N-glycosylation.", "protein": "ALG12", "protein_enriched": { "function": "Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-link", "gene_name": "ALG12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9BV10" }, "relationship_type": "causal", "source_pmcid": "PMC11846398" }, { "confidence": "high", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "gE is heavily glycosylated, facilitating immune evasion and vascular tropism.", "mechanism": "VZV gE mediates viral entry and spread in vascular tissue, leading to vasculitis.", "protein": "Varicella Zoster Virus glycoprotein E (gE)", "protein_enriched": { "function": "Glycoprotein that probably modulates membrane fusion events during secondary envelopment of cytoplasmic capsids that bud into specific trans-Golgi network (TGN)-derived membranes. Also plays a role, t", "gene_name": "gK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09261" }, "relationship_type": "causal", "source_pmcid": "PMC11846706" }, { "confidence": "high", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "IgG glycosylation modulates antibody effector functions and CNS penetration.", "mechanism": "Elevated VZV-specific IgG antibody index in CSF indicates intrathecal synthesis and active CNS infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846706" }, { "confidence": "high", "disease": "Intracranial hemorrhage", "glycan_involvement": "Glycosylation of gE enhances its interaction with host cells and immune modulation.", "mechanism": "VZV gE presence in vascular walls triggers inflammation and vessel wall weakening, resulting in hemorrhage.", "protein": "Varicella Zoster Virus glycoprotein E (gE)", "protein_enriched": { "function": "Glycoprotein that probably modulates membrane fusion events during secondary envelopment of cytoplasmic capsids that bud into specific trans-Golgi network (TGN)-derived membranes. Also plays a role, t", "gene_name": "gK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09261" }, "relationship_type": "causal", "source_pmcid": "PMC11846706" }, { "confidence": "medium", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "IL-6 glycosylation affects its stability and receptor binding.", "mechanism": "Elevated CSF IL-6 reflects vascular inflammation and immune activation in VZV vasculopathy.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846706" }, { "confidence": "medium", "disease": "Intracranial hemorrhage", "glycan_involvement": "IgG glycosylation influences CNS immune response.", "mechanism": "High VZV IgG index in CSF correlates with active CNS infection and risk of hemorrhagic complications.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846706" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation of gE is critical for vascular cell interaction.", "mechanism": "VZV gE-mediated vascular inflammation can also lead to vessel occlusion and ischemic stroke.", "protein": "Varicella Zoster Virus glycoprotein E (gE)", "protein_enriched": { "function": "Glycoprotein that probably modulates membrane fusion events during secondary envelopment of cytoplasmic capsids that bud into specific trans-Golgi network (TGN)-derived membranes. Also plays a role, t", "gene_name": "gK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09261" }, "relationship_type": "causal", "source_pmcid": "PMC11846706" }, { "confidence": "medium", "disease": "Intracranial hemorrhage", "glycan_involvement": "IL-6 glycosylation modulates its inflammatory activity.", "mechanism": "CSF IL-6 elevation is associated with acute vascular inflammation and hemorrhage.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846706" }, { "confidence": "medium", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "Glycosylation of gE may affect drug sensitivity.", "mechanism": "Antiviral drugs (acyclovir) target VZV replication, indirectly reducing gE-mediated vascular damage.", "protein": "Varicella Zoster Virus glycoprotein E (gE)", "protein_enriched": { "function": "Glycoprotein that probably modulates membrane fusion events during secondary envelopment of cytoplasmic capsids that bud into specific trans-Golgi network (TGN)-derived membranes. Also plays a role, t", "gene_name": "gK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09261" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846706" }, { "confidence": "low", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "IgG glycosylation affects antibody-mediated viral clearance.", "mechanism": "Intrathecal IgG response may help control VZV infection in CNS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11846706" }, { "confidence": "high", "disease": "Varicella Zoster Virus vasculopathy", "glycan_involvement": "Glycosylation is essential for antigenicity and detection.", "mechanism": "Detection of gE antigen in vascular walls by immunohistochemistry confirms VZV involvement.", "protein": "Varicella Zoster Virus glycoprotein E (gE)", "protein_enriched": { "function": "Glycoprotein that probably modulates membrane fusion events during secondary envelopment of cytoplasmic capsids that bud into specific trans-Golgi network (TGN)-derived membranes. Also plays a role, t", "gene_name": "gK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09261" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846706" }, { "confidence": "high", "disease": "Human cytomegalovirus infection", "glycan_involvement": "Glycosylation of UL148 modulates its function in host cell interaction.", "mechanism": "UL148 is a viral glycoprotein involved in HCMV cell tropism and immune evasion, contributing to infection establishment.", "protein": "UL148", "protein_enriched": { "function": "", "gene_name": "UL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F5H984" }, "relationship_type": "causal", "source_pmcid": "PMC11846927" }, { "confidence": "medium", "disease": "Congenital cytomegalovirus disease", "glycan_involvement": "Glycosylation status may affect UL148-mediated immune modulation in the placenta.", "mechanism": "UL148 genetic variants may influence HCMV virulence and transmission in congenital infections.", "protein": "UL148", "protein_enriched": { "function": "", "gene_name": "UL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F5H984" }, "relationship_type": "causal", "source_pmcid": "PMC11846927" }, { "confidence": "medium", "disease": "Cytomegalovirus disease in immunocompromised patients", "glycan_involvement": "Glycosylation of UL148 may affect recognition by host immune cells.", "mechanism": "UL148 variants may alter immune evasion, impacting disease severity in immunocompromised hosts.", "protein": "UL148", "protein_enriched": { "function": "", "gene_name": "UL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F5H984" }, "relationship_type": "causal", "source_pmcid": "PMC11846927" }, { "confidence": "high", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "CK7 is a mucin-type glycoprotein; glycosylation affects stability and localization", "mechanism": "CK7 positivity in tumor cells aids in confirming epithelial origin of SRPC", "protein": "Cytokeratin 7 (CK7)", "protein_enriched": { "function": "Blocks interferon-dependent interphase and stimulates DNA synthesis in cells. Involved in the translational regulation of the human papillomavirus type 16 E7 mRNA (HPV16 E7)", "gene_name": "KRT7", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08729" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "high", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "Glycosylation modulates cytokeratin filament assembly", "mechanism": "PCK positivity confirms epithelial differentiation in SRPC", "protein": "Cytokeratin (PCK)", "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "high", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "Vimentin is glycosylated, which can affect filament organization", "mechanism": "Vimentin positivity indicates mesenchymal/sarcomatoid differentiation in SRPC", "protein": "Vimentin (Vim)", "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "medium", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "GATA-3 is glycosylated, influencing nuclear localization", "mechanism": "Partial GATA-3 positivity supports urothelial origin", "protein": "GATA-3", "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "high", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "P53 glycosylation can affect stability and function", "mechanism": "High mutant P53 expression indicates tumor aggressiveness", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "medium", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "CK20 is glycosylated, affecting filament properties", "mechanism": "CK20 negativity helps distinguish SRPC from other urothelial carcinomas", "protein": "CK20", "protein_enriched": { "function": "Plays a significant role in maintaining keratin filament organization in intestinal epithelia. When phosphorylated, plays a role in the secretion of mucin in the small intestine (By similarity)", "gene_name": "KRT20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35900" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "medium", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "PAX-8 is glycosylated, modulating DNA binding", "mechanism": "PAX-8 negativity helps exclude renal cell carcinoma origin", "protein": "PAX-8", "protein_enriched": { "function": "Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells", "gene_name": "PAX8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q06710" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "high", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "Ki-67 is glycosylated, affecting nuclear function", "mechanism": "High Ki-67 index indicates high proliferative activity in SRPC", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "medium", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "P40 is glycosylated, influencing transcriptional activity", "mechanism": "P40 negativity helps rule out squamous differentiation", "protein": "P40", "protein_enriched": { "function": "Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showin", "gene_name": "TP63", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H3D4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "medium", "disease": "Sarcomatoid renal pelvis carcinoma (SRPC)", "glycan_involvement": "SMA glycosylation affects filament assembly", "mechanism": "Partial SMA positivity indicates sarcomatoid (mesenchymal) differentiation", "protein": "Smooth Muscle Actin (SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11847286" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (CDG)", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins.", "mechanism": "Mutations in DHDDS impair dolichol synthesis, disrupting N-glycosylation.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (CDG)", "glycan_involvement": "Defective N-glycosylation of glycoproteins.", "mechanism": "NgBR forms a complex with DHDDS; mutations impair dolichol synthesis and N-glycosylation.", "protein": "NgBR (NUS1)", "relationship_type": "causal", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Niemann-Pick Disease Type C (NPC)", "glycan_involvement": "NPC2 is a glycoprotein; glycosylation is required for its stability and function.", "mechanism": "Loss-of-function mutations in NPC2 block lysosomal cholesterol export.", "protein": "NPC2", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:11125141, PubMed:15937921, PubMed:", "gene_name": "NPC2", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G28681TP", "G41247ZX", "G05049YU", "G06110VR", "G07810QS", "G14669DU", "G18647XP", "G23719VF", "G27915IV", "G31852PQ", "G34989PA", "G37818NZ", "G37995HC", "G43223CG", "G43734MM", "G45504EY", "G46691LC", "G54010QB", "G57317CE", "G57776ZS", "G62765YT", "G65344XH", "G69521XL", "G73027HY", "G80920RR", "G85282JO", "G87661QW", "G89045VA", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "P61916" }, "relationship_type": "causal", "source_pmcid": "PMC11855410" }, { "confidence": "medium", "disease": "DHDDS/NUS1-associated neurodevelopmental syndrome", "glycan_involvement": "Indirect; DHDDS/NgBR mutations affect NPC2 stability/localization.", "mechanism": "NPC2 mislocalization and functional impairment due to DHDDS/NgBR mutations leads to NPC-like cellular phenotypes.", "protein": "NPC2", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:11125141, PubMed:15937921, PubMed:", "gene_name": "NPC2", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G28681TP", "G41247ZX", "G05049YU", "G06110VR", "G07810QS", "G14669DU", "G18647XP", "G23719VF", "G27915IV", "G31852PQ", "G34989PA", "G37818NZ", "G37995HC", "G43223CG", "G43734MM", "G45504EY", "G46691LC", "G54010QB", "G57317CE", "G57776ZS", "G62765YT", "G65344XH", "G69521XL", "G73027HY", "G80920RR", "G85282JO", "G87661QW", "G89045VA", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "P61916" }, "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Niemann-Pick Disease Type C (NPC)", "glycan_involvement": "LAMP1 is a heavily glycosylated lysosomal protein.", "mechanism": "LAMP1 is elevated in NPC due to lysosomal expansion from lipid storage.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "DHDDS/NUS1-associated neurodevelopmental syndrome", "glycan_involvement": "LAMP1 glycosylation status not altered, but protein is upregulated.", "mechanism": "LAMP1 is elevated in DHDDS patient cells, indicating lysosomal expansion.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (CDG)", "glycan_involvement": "Altered N-glycosylation patterns in most CDGs, but normal in DHDDS heterozygotes.", "mechanism": "Transferrin N-glycosylation profile is a diagnostic marker for CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Niemann-Pick Disease Type C (NPC)", "glycan_involvement": "GM1 is a glycosphingolipid; its accumulation reflects glycan storage.", "mechanism": "GM1 accumulates in lysosomes due to impaired lipid trafficking.", "protein": "Ganglioside GM1", "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "DHDDS/NUS1-associated neurodevelopmental syndrome", "glycan_involvement": "Reflects secondary glycosphingolipid storage due to glycosylation pathway disruption.", "mechanism": "GM1 accumulates in lysosomes of DHDDS patient cells, mimicking NPC.", "protein": "Ganglioside GM1", "relationship_type": "biomarker", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Niemann-Pick Disease Type C (NPC)", "glycan_involvement": "NPC1 is glycosylated; glycosylation is important for function.", "mechanism": "NPC1 mutations cause lysosomal cholesterol and glycosphingolipid accumulation.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC11855410" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy", "glycan_involvement": "Dystrophin anchors the glycoprotein complex; glycosylation of complex components is essential for membrane stability.", "mechanism": "Loss or dysfunction of dystrophin leads to muscle membrane fragility and progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of complex components is required for proper membrane-cytoskeleton linkage.", "mechanism": "Dystrophin deficiency destabilizes the dystrophin\u2013glycoprotein complex in cardiac muscle, leading to cardiomyocyte damage and DCM.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy", "glycan_involvement": "Complex contains glycosylated proteins (e.g., dystroglycans) critical for function.", "mechanism": "Disruption of the complex due to dystrophin loss impairs force transmission and membrane integrity.", "protein": "Dystrophin\u2013glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of dystroglycans is essential for extracellular matrix binding.", "mechanism": "Loss of complex integrity in cardiac muscle leads to increased membrane permeability and cardiac dysfunction.", "protein": "Dystrophin\u2013glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Indirect, via destabilization of glycoprotein complex.", "mechanism": "Dystrophin deficiency leads to cardiac conduction abnormalities.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Indirect, via glycoprotein complex disruption.", "mechanism": "Progressive cardiac muscle degeneration due to dystrophin loss leads to heart failure.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11855830" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Not directly related to glycosylation, but impacts glycoprotein complex stability.", "mechanism": "Specific DMD gene exon deletions (e.g., exons 12, 14\u201317, 31\u201342, 45, 48\u201349, 55) are associated with increased cardiac risk.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC11855830" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy", "glycan_involvement": "Therapies aim to restore glycoprotein complex function, which depends on glycosylation.", "mechanism": "Restoration of dystrophin or complex integrity is a target for gene/exon-skipping therapies.", "protein": "Dystrophin\u2013glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11855830" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Restored dystrophin supports glycoprotein complex assembly and glycosylation-dependent interactions.", "mechanism": "Gene therapy and exon skipping aim to restore dystrophin and prevent cardiac dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11855830" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of dystroglycans is critical for therapy efficacy.", "mechanism": "Targeting the complex or its glycosylation may improve cardiac outcomes.", "protein": "Dystrophin\u2013glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11855830" }, { "confidence": "high", "disease": "CVID", "glycan_involvement": "Unique hypersialylation (\u03b12,6) and hyperfucosylation (\u03b11,3/4/6, core fucose, SLeX) on cell surface.", "mechanism": "Expansion of CD21 low B cells correlates with immune dysregulation in CVID.", "protein": "CD21 low B cells", "relationship_type": "biomarker", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Upregulation of ST6GALNAC4/6, FUT8, SLeX, hypersialylation/hyperfucosylation.", "mechanism": "Expansion of CD21 low/CD11c high B cells in SLE with similar glycosylation gene expression.", "protein": "CD21 low B cells", "relationship_type": "biomarker", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "Elevated SLeX enhances selectin-mediated migration to inflamed tissues.", "mechanism": "CD21 low B cells accumulate in inflamed joints, possibly via SLeX-mediated trafficking.", "protein": "CD21 low B cells", "relationship_type": "causal", "source_pmcid": "PMC11861550" }, { "confidence": "high", "disease": "CVID", "glycan_involvement": "Hypersialylation/hyperfucosylation alters lectin-ligand interactions and immune cell function.", "mechanism": "Altered glycosylation may affect B-cell function and contribute to immune dysregulation.", "protein": "CD21 low B cells", "relationship_type": "causal", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "CVID", "glycan_involvement": "Sialylation/fucosylation of IgG confers anti-inflammatory properties.", "mechanism": "\u03b12,6 sialylation and fucosylation of IgG reduce ADCC and inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "CVID", "glycan_involvement": "Reduced terminal \u03b21,4 galactose limits galectin 1 secretion.", "mechanism": "Reduced secretion of galectin 1 by CD21 low B cells may favor Th1 bias.", "protein": "Galectin 1", "protein_enriched": { "function": "Lectin that binds beta-galactoside and a wide array of complex carbohydrates. Plays a role in regulating apoptosis, cell proliferation and cell differentiation. Inhibits CD45 protein phosphatase activ", "gene_name": "LGALS1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P09382" }, "relationship_type": "causal", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Increased sialylation, core fucosylation, and SLeX facilitate tumor cell interactions.", "mechanism": "Similar glycan changes in tumor cells promote migration, survival, and immune evasion.", "protein": "CD21 low B cells", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "Autoimmune Cytopenia", "glycan_involvement": "Characteristic hypersialylation/hyperfucosylation.", "mechanism": "CD21 low B cell expansion associated with autoimmune cytopenia in CVID.", "protein": "CD21 low B cells", "relationship_type": "biomarker", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "GLILD", "glycan_involvement": "Unique glycosylation pattern present.", "mechanism": "CD21 low B cell expansion linked to GLILD in CVID.", "protein": "CD21 low B cells", "relationship_type": "biomarker", "source_pmcid": "PMC11861550" }, { "confidence": "medium", "disease": "Lymphoproliferation", "glycan_involvement": "Hypersialylation/hyperfucosylation.", "mechanism": "CD21 low B cell expansion associated with lymphoproliferative complications in CVID.", "protein": "CD21 low B cells", "relationship_type": "biomarker", "source_pmcid": "PMC11861550" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Aberrant sialylation and Tn antigen exposure on O-glycans.", "mechanism": "Altered O-glycosylation of mucins is associated with tumor progression and immune evasion.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Core 1 and sialylated O-glycans regulate CD24 function.", "mechanism": "CD24 O-glycosylation modulates cell adhesion and metastatic potential.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC11861894" }, { "confidence": "medium", "disease": "Immunity dysfunction", "glycan_involvement": "Mono- and di-sialylCore 1/2 O-glycans.", "mechanism": "Sialylated O-glycans on fetuin influence immune modulation and inflammation.", "protein": "Fetuin", "relationship_type": "biomarker", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Drug efficacy/safety issues", "glycan_involvement": "Sialylated Core 1 O-glycans are major modifications.", "mechanism": "O-glycosylation impacts stability, immunogenicity, and efficacy of biotherapeutic.", "protein": "Etanercept", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Drug efficacy/safety issues", "glycan_involvement": "Sialylated Core 1 O-glycans.", "mechanism": "O-glycosylation affects pharmacokinetics and safety profile.", "protein": "Abatacept", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Infectious disease (bacterial colonization)", "glycan_involvement": "Core 1/2/3 O-glycans and sialylated structures.", "mechanism": "O-glycans serve as ligands for bacterial adhesins, mediating colonization and invasion.", "protein": "General epithelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Unextended GalNAc\u03b1-O-Ser/Thr (Tn antigen).", "mechanism": "Exposure of Tn antigen is a hallmark of malignant transformation.", "protein": "Tn antigen-bearing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11861894" }, { "confidence": "medium", "disease": "Glycosylation disorders", "glycan_involvement": "Altered core structures and sialylation.", "mechanism": "Defects in O-glycan biosynthesis lead to abnormal protein function and disease.", "protein": "Core 1/2/3/6 O-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC11861894" }, { "confidence": "medium", "disease": "Cell adhesion disorders", "glycan_involvement": "Gal\u03b21,3GlcNAc motifs.", "mechanism": "Type-I chain N-glycans modulate cell-cell and cell-matrix interactions.", "protein": "Type-I chain N-glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11861894" }, { "confidence": "medium", "disease": "Host-microbe interaction disorders", "glycan_involvement": "GalNAc\u03b21,3Gal motifs.", "mechanism": "Glycolipid glycan motifs serve as microbial binding sites, affecting host-microbe symbiosis.", "protein": "Globo-series glycolipids", "relationship_type": "causal", "source_pmcid": "PMC11861894" }, { "confidence": "high", "disease": "Cognitive impairment/neurodevelopmental disorders", "glycan_involvement": "Polysialylation (Neu5Ac-rich) of NCAM", "mechanism": "PolySia-NCAM complexes promote synaptic plasticity and neurodevelopment; Neu5Ac supplementation enhances NCAM sialylation and brain development.", "protein": "NCAM (Neural Cell Adhesion Molecule)", "relationship_type": "protective", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Sialylation and O-acetylation of glycan chains", "mechanism": "Overexpression and O-acetylation of gangliosides (sialylated glycolipids) promote tumor growth, proliferation, and metastasis.", "protein": "Gangliosides", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Metabolic diseases (e.g., obesity-related hypertension)", "glycan_involvement": "Sialylation of Fc N-glycans", "mechanism": "Reduced IgG sialylation in high-fat diet mice increases blood pressure; sialylation modulates immune response and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11865545" }, { "confidence": "medium", "disease": "Cancer (immune evasion)", "glycan_involvement": "O-glycosylation with terminal \u03b12,6-linked sialic acid", "mechanism": "\u03b12,6-sialylated Mucin 2 binds Siglec-3, inducing apoptosis of dendritic cells and inhibiting antitumor T-cell responses.", "protein": "Mucin 2", "protein_enriched": { "function": "Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces (PubMed:170580", "gene_name": "MUC2", "glycan_count": 55, "glycosylation_sites_count": 45, "glytoucan_ids": [ "G31976RQ", "G22768VO", "G36191CD", "G78059CC", "G00031MO", "G00035MO", "G03172PR", "G03494YC", "G03674DU", "G07932PU", "G10256JP", "G14260UH", "G17810KS", "G19399OS", "G23438NR", "G23870PO", "G25780HH", "G26493RP", "G26915XM", "G27726WH", "G29025YS", "G29931IJ", "G30304IT", "G31685JQ", "G31936TA", "G32405GG", "G32550BI", "G32723SL", "G36447PT", "G38684VZ", "G38887TM", "G39247UK", "G42665KV", "G45939NL", "G49277CJ", "G49582PC", "G50757KG", "G51140AE", "G52902AR", "G54567CI", "G58272ZE", "G58972ZH", "G60554YG", "G61889LW", "G63334FZ", "G63628AV", "G64931FF", "G64973KT", "G69233PF", "G71838YU", "G73423PD", "G74722FL", "G76163CP", "G85228QD", "G94435QH" ], "uniprot_id": "Q02817" }, "relationship_type": "causal", "source_pmcid": "PMC11865545" }, { "confidence": "medium", "disease": "Cancer (immune evasion)", "glycan_involvement": "Recognition of sialylated glycoproteins", "mechanism": "Binds sialoglycans on tumor cells, inhibiting complement activation and promoting tumor survival.", "protein": "Factor H", "relationship_type": "causal", "source_pmcid": "PMC11865545" }, { "confidence": "medium", "disease": "Cancer (immune evasion)", "glycan_involvement": "Sialylated glycan epitope on glycoproteins", "mechanism": "Sialyl Lewis X on tumor cells modulates NK cell activation and immune evasion.", "protein": "Sialyl Lewis X", "relationship_type": "causal", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Cancer (immune evasion)", "glycan_involvement": "Recognition of terminal sialic acids on glycoproteins", "mechanism": "Siglec binding to sialoglycans on tumor cells suppresses immune cell activation (NK, macrophages, dendritic cells).", "protein": "Siglecs (e.g., Siglec-3, Siglec-9, Siglec-15)", "relationship_type": "causal", "source_pmcid": "PMC11865545" }, { "confidence": "medium", "disease": "Viral infections (e.g., influenza)", "glycan_involvement": "Sialylation of glycoprotein", "mechanism": "Sialylated ovomucin binds viral hemagglutinin, blocking viral entry.", "protein": "Ovomucin", "relationship_type": "protective", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Cognitive impairment/neurodevelopmental disorders", "glycan_involvement": "Sialylation (\u03b12,3/\u03b12,6) of oligosaccharides", "mechanism": "Sialylated HMOs (e.g., 3'-SL, 6'-SL) provide Neu5Ac for brain development, improving cognition and memory in infants.", "protein": "Sialylated Human Milk Oligosaccharides (HMOs)", "relationship_type": "protective", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Inflammatory diseases (e.g., atherosclerosis, heart failure)", "glycan_involvement": "Sialylation of Fc N-glycans", "mechanism": "Serum sialylation status of IgG correlates with inflammation and disease severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11865545" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Fibulin 1 is a glycoprotein; glycosylation may affect its stability and ECM interactions.", "mechanism": "Serum Fibulin 1 levels are elevated in symptomatic HF and decrease with treatment, correlating with NT-proBNP and inversely with LVEF.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy", "glycan_involvement": "Fibulin 2 is a glycoprotein; glycosylation may modulate ECM remodeling.", "mechanism": "Fibulin 2 levels are increased in serum and myocardium of HCM patients, reflecting tissue fibrosis.", "protein": "Fibulin 2", "protein_enriched": { "function": "Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN (PubMed:17255108)", "gene_name": "FBLN2", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10488MI", "G11314AS", "G14994KB", "G18647XP", "G20706XG", "G23863VK", "G27058EU", "G29880MM", "G36379GD", "G37509XX", "G41071NU", "G42124LM", "G46687AB", "G47644PP", "G57776ZU", "G59924QI", "G77669RF", "G80223IX", "G80920RR", "G84452RH", "G84862VB", "G90659AW", "G13144LI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G57321FI", "G49108TO", "G57317CE", "G25451PN", "G62765YT", "G71142DF" ], "uniprot_id": "P98095" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation may influence Fibulin 1\u2019s ECM localization and function.", "mechanism": "Plasma Fibulin 1 is elevated in diabetic patients, associated with vascular remodeling and increased arterial fibrosis.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Aortic Stenosis", "glycan_involvement": "Glycosylation may affect Fibulin 1\u2019s role in ECM remodeling.", "mechanism": "Fibulin 1 levels correlate with NT-proBNP and predict cardiac mortality post-valve replacement.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may influence Fibulin 1\u2019s response to therapy.", "mechanism": "Spironolactone treatment reduces Fibulin 1 levels in diabetic-resistant hypertension, suggesting a role in fibrosis modulation.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease", "glycan_involvement": "Glycosylation may affect Fibulin 1\u2019s ECM interactions and fibrotic activity.", "mechanism": "Fibulin 1 is increased in bronchoepithelial cells and serum; inhibition reduces airway collagen deposition.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "causal", "source_pmcid": "PMC11868881" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Fibulin 2 glycosylation status not specifically discussed.", "mechanism": "No significant change in serum Fibulin 2 levels across HF stages or with treatment; limited biomarker utility in HF.", "protein": "Fibulin 2", "protein_enriched": { "function": "Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN (PubMed:17255108)", "gene_name": "FBLN2", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10488MI", "G11314AS", "G14994KB", "G18647XP", "G20706XG", "G23863VK", "G27058EU", "G29880MM", "G36379GD", "G37509XX", "G41071NU", "G42124LM", "G46687AB", "G47644PP", "G57776ZU", "G59924QI", "G77669RF", "G80223IX", "G80920RR", "G84452RH", "G84862VB", "G90659AW", "G13144LI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G57321FI", "G49108TO", "G57317CE", "G25451PN", "G62765YT", "G71142DF" ], "uniprot_id": "P98095" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Cardiac Remodeling", "glycan_involvement": "Glycosylation may regulate Fibulin 2\u2019s ECM function.", "mechanism": "Experimental models implicate Fibulin 2 in hypertrophic response to angiotensin II and cardiac remodeling.", "protein": "Fibulin 2", "protein_enriched": { "function": "Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN (PubMed:17255108)", "gene_name": "FBLN2", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10488MI", "G11314AS", "G14994KB", "G18647XP", "G20706XG", "G23863VK", "G27058EU", "G29880MM", "G36379GD", "G37509XX", "G41071NU", "G42124LM", "G46687AB", "G47644PP", "G57776ZU", "G59924QI", "G77669RF", "G80223IX", "G80920RR", "G84452RH", "G84862VB", "G90659AW", "G13144LI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G57321FI", "G49108TO", "G57317CE", "G25451PN", "G62765YT", "G71142DF" ], "uniprot_id": "P98095" }, "relationship_type": "causal", "source_pmcid": "PMC11868881" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "NT-proBNP is glycosylated, affecting its stability and clearance.", "mechanism": "NT-proBNP is a well-established biomarker for HF diagnosis and prognosis; levels decrease with treatment.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11868881" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may influence Fibulin 1\u2019s therapeutic response.", "mechanism": "Fibulin 1 levels decrease with HF treatment (e.g., RAAS blockade, metformin), suggesting modulation of fibrosis.", "protein": "Fibulin 1", "protein_enriched": { "function": "Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain develo", "gene_name": "FBLN1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G29068FM", "G04657PL", "G27058EU", "G43669FQ", "G45395BF", "G46691LC", "G65019XG", "G77669RF", "G84452RH", "G94470IW", "G18227ZU", "G05962QB", "G07246CJ", "G08293MJ", "G10488MI", "G11629QQ", "G12341GU", "G14972EH", "G15169WU", "G15664MX", "G20706XG", "G23863VK", "G27126ED", "G28622IK", "G40834TG", "G41071NU", "G43223CG", "G47644PP", "G53075ES", "G57776ZS", "G62765YT", "G63041LO", "G63980BQ", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84225JN", "G84862VB", "G87123QX", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G92275SC", "G93718GY", "G94917XT", "G49108TO" ], "uniprot_id": "P23142" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11868881" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Indirect; dystrophin anchors glycoprotein complexes.", "mechanism": "Loss-of-function mutations in dystrophin gene disrupt muscle fiber integrity.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation of alpha-dystroglycan critical for ECM binding.", "mechanism": "Disruption of DAG1-dystrophin interaction destabilizes sarcolemma.", "protein": "Dystroglycan 1 (DAG1)", "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation required for complex stability.", "mechanism": "SGCD loss impairs sarcoglycan complex, compromising membrane integrity.", "protein": "Sarcoglycan delta (SGCD)", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "KPNA5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15131" }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation modulates membrane localization.", "mechanism": "SGCE disruption accelerates muscle degeneration.", "protein": "Sarcoglycan epsilon (SGCE)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P38398" }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential O-glycosylation; not specified.", "mechanism": "SSPN loss destabilizes dystrophin-glycoprotein complex.", "protein": "Sarcospan (SSPN)", "protein_enriched": { "function": "Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface", "gene_name": "SCAMP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15127" }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct glycosylation; interacts with glycoprotein complexes.", "mechanism": "Upregulation compensates for dystrophin deficiency.", "protein": "Utrophin (UTRN)", "relationship_type": "protective", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation essential for function.", "mechanism": "Defective glycosylation impairs ECM binding, exacerbating muscle weakness.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation affects ECM interactions.", "mechanism": "LAMA2 interacts with glycosylated alpha-dystroglycan; disruption worsens phenotype.", "protein": "Laminin subunit alpha-2 (LAMA2)", "relationship_type": "modifier", "source_pmcid": "PMC11871439" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "O-glycosylation required for neural signaling.", "mechanism": "Defective glycosylation of DAG1 in CNS impairs synaptic function.", "protein": "Dystroglycan 1 (DAG1)", "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "N-glycosylation modulates cardiac membrane stability.", "mechanism": "SGCD dysfunction leads to myocardial fibrosis and cardiac failure.", "protein": "Sarcoglycan delta (SGCD)", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "KPNA5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15131" }, "relationship_type": "causal", "source_pmcid": "PMC11871439" }, { "confidence": "high", "disease": "Alzheimer disease", "glycan_involvement": "Sialylation of Trem2 modulates its signaling and processing; hyper-sialylation (due to NEU1 deficiency) impairs phagocytosis and enhances pro-inflammatory signaling.", "mechanism": "Trem2 regulates microglial survival, phagocytosis, and cytokine production; altered sialylation impairs these functions and promotes neuroinflammation.", "protein": "Trem2", "relationship_type": "causal", "source_pmcid": "PMC11874873" }, { "confidence": "high", "disease": "Sialidosis", "glycan_involvement": "Loss of NEU1 leads to hyper-sialylation of glycoproteins including Trem2 and APP.", "mechanism": "NEU1 deficiency causes lysosomal storage, neurodegeneration, and microglial dysfunction.", "protein": "NEU1", "protein_enriched": { "function": "Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears t", "gene_name": "NEU1", "glycan_count": 32, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10486CT", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G35029YA", "G37995HC", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G49642SA", "G49955PK", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G72787SB", "G72790NZ", "G83646BJ", "G85282JO", "G87661QW", "G90659AW", "G92275SC", "G95177YH", "G15664MX", "G80920RR", "G49108TO" ], "uniprot_id": "Q99519" }, "relationship_type": "causal", "source_pmcid": "PMC11874873" }, { "confidence": "high", "disease": "Sialidosis", "glycan_involvement": "Sialylation of Trem2 increases due to NEU1 loss, altering its function.", "mechanism": "In NEU1-deficient (sialidosis) mice, sialylated Trem2 accumulates, is aberrantly processed, and drives microglial pro-inflammatory phenotype.", "protein": "Trem2", "relationship_type": "causal", "source_pmcid": "PMC11874873" }, { "confidence": "high", "disease": "Alzheimer disease", "glycan_involvement": "NEU1 deficiency leads to increased sialylation and lysosomal accumulation of APP.", "mechanism": "Sialylated APP accumulates in lysosomes, is processed into amyloid-beta, and released via exocytosis, promoting amyloidosis.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "NEU1 normally desialylates LAMP1; deficiency increases sialylation and exocytosis.", "mechanism": "Sialylated LAMP1 has increased half-life, promoting lysosomal exocytosis and release of neurotoxic peptides.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "causal", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Frontotemporal lobar dementia", "glycan_involvement": "NEU1 downregulation and Trem2 sialylation observed in disease datasets.", "mechanism": "Trem2 dysfunction and altered sialylation implicated in microglial-mediated neuroinflammation.", "protein": "Trem2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Altered Trem2 sialylation due to NEU1 downregulation.", "mechanism": "Trem2-dependent microglial activation and neuroinflammation; NEU1 downregulation may exacerbate pathology.", "protein": "Trem2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Altered glycosylation patterns inferred.", "mechanism": "NEU1 and Trem2 downregulation associated with microglial dysfunction in disease datasets.", "protein": "Trem2", "relationship_type": "biomarker", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Normal aging", "glycan_involvement": "Increased sialylation of Trem2 with age due to NEU1 decline.", "mechanism": "NEU1 downregulation and Trem2 sialylation may contribute to age-related microglial dysfunction and neuroinflammation.", "protein": "Trem2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11874873" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Sialic acid binding and glycosylation status influence CD33 function.", "mechanism": "CD33, a sialoglycoprotein, modulates Trem2 signaling and is upregulated in NEU1-deficient microglia.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11874873" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "TLR4 glycosylation modulates ligand binding and signaling.", "mechanism": "TLR4 activation by LPS induces mTOR phosphorylation and NF-\u03baB pathway, promoting inflammation and insulin resistance.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects nuclear translocation and stability.", "mechanism": "NF-\u03baB activation drives transcription of pro-inflammatory cytokines, exacerbating insulin resistance.", "protein": "NF-\u03baB (p65)", "relationship_type": "causal", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated IL-6 correlates with systemic inflammation and metabolic dysfunction in T2DM.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation essential for anti-inflammatory activity.", "mechanism": "IL-10 suppresses inflammatory cytokine production, improving insulin sensitivity.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 promotes insulin resistance and \u03b2-cell dysfunction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation required for maturation and secretion.", "mechanism": "IL-1\u03b2 induces \u03b2-cell apoptosis and inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11879814" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation modulates cytokine stability.", "mechanism": "IL-17A drives neutrophil recruitment and tissue inflammation.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation regulates membrane localization and barrier function.", "mechanism": "Reduced occludin disrupts tight junctions, increasing gut permeability and inflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC11879814" }, { "confidence": "medium", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation affects tight junction assembly.", "mechanism": "Decreased claudin-1 impairs tight junction integrity, contributing to metabolic endotoxemia.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "biomarker", "source_pmcid": "PMC11879814" }, { "confidence": "medium", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation modulates protein-protein interactions in tight junctions.", "mechanism": "Reduced ZO-1 correlates with increased intestinal permeability and inflammation.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC11879814" }, { "confidence": "high", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation required for viral infectivity and immune evasion.", "mechanism": "Mediates viral entry and spread in neurons; detected in infected organoids.", "protein": "LACV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11881317" }, { "confidence": "high", "disease": "Orthobunyavirus encephalitis", "glycan_involvement": "Glycosylation modulates membrane localization and antiviral activity.", "mechanism": "Restricts viral entry and replication in neurons; upregulated in protected regions.", "protein": "IFITM3", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P14210" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "high", "disease": "Orthobunyavirus encephalitis", "glycan_involvement": "N-glycosylation essential for antiviral function.", "mechanism": "Prevents viral particle release from infected cells; upregulated in protective neuronal regions.", "protein": "BST2 (Tetherin)", "protein_enriched": { "function": "Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR) (PubMed:7805847). Cyclic ADPR is known to serve as an endogenous second messenge", "gene_name": "BST1", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G10486CT", "G31852PQ", "G39188ZX", "G41247ZX", "G49018RC", "G59626AS", "G62765YT", "G72747WU", "G77547TA", "G78787DI", "G90659AW", "G04657PL", "G08293MJ", "G27058EU", "G41071NU", "G42124LM", "G47644PP", "G84452RH", "G14972EH", "G79666IR", "G83646BJ", "G87661QW" ], "uniprot_id": "Q10588" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "medium", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation may affect protein stability and antiviral activity.", "mechanism": "Inhibits viral replication; upregulated in bystander neural progenitors.", "protein": "MX1", "protein_enriched": { "function": "Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses. Its target viruses include negative-stranded RNA viruses and HBV through bindin", "gene_name": "MX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20591" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "medium", "disease": "La Crosse virus encephalitis", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Modulates innate immune signaling and restricts viral infection.", "protein": "AXL", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell", "gene_name": "AXL", "glycan_count": 14, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G27058EU", "G84452RH", "G11629QQ", "G12793SR", "G15169WU", "G48414YA", "G52527GH", "G60834IK", "G62765YT", "G81263BG", "G89205CJ", "G93656SY", "G90575OW" ], "uniprot_id": "P30530" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "high", "disease": "La Crosse virus encephalitis", "glycan_involvement": "N-glycosylation required for cell surface expression and signaling.", "mechanism": "Type I IFN receptor mediates antiviral signaling; knockout increases viral spread.", "protein": "IFNAR1", "protein_enriched": { "function": "Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2", "gene_name": "IFNAR1", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G22310AV", "G13694XX", "G81263BG", "G25079LO", "G06356OH", "G33791AF", "G86795LJ", "G62765YT", "G75983OB", "G04657PL", "G41071NU", "G93656SY", "G80920RR" ], "uniprot_id": "P17181" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "medium", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation may influence enzymatic activity.", "mechanism": "Activates RNase L pathway to degrade viral RNA; upregulated in protected regions.", "protein": "OAS1", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular process", "gene_name": "OAS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00973" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "medium", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation may influence enzymatic activity.", "mechanism": "Similar to OAS1; upregulated in bystander neural progenitors.", "protein": "OAS2", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA ", "gene_name": "OAS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P29728" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "medium", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation may influence enzymatic activity.", "mechanism": "Similar to OAS1/2; upregulated in protected neuronal regions.", "protein": "OAS3", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptos", "gene_name": "OAS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K5" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "high", "disease": "La Crosse virus encephalitis", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Blocks translation of viral RNA; highly expressed in bystander neural progenitors.", "protein": "IFIT1", "protein_enriched": { "function": "Plays a key role in the innate immune response as part of an interferon-dependent multiprotein complex, recognizing and sequestering viral RNAs that lack host-specific 2'-O-methylation at their 5' cap", "gene_name": "IFIT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09914" }, "relationship_type": "protective", "source_pmcid": "PMC11881317" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Dystrophin is part of the dystrophin-associated glycoprotein complex, which contains glycosylated proteins essential for sarcolemma stability.", "mechanism": "Loss-of-function mutations in the DMD gene lead to absence or severe reduction of dystrophin, compromising muscle fiber integrity.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887092" }, { "confidence": "high", "disease": "Becker muscular dystrophy", "glycan_involvement": "Glycosylation of DGC components is critical for complex stability; altered dystrophin affects DGC glycoprotein interactions.", "mechanism": "Missense mutations in the DMD gene allow production of partially functional dystrophin, resulting in milder muscle weakness.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887092" }, { "confidence": "medium", "disease": "X-linked dystrophinopathy", "glycan_involvement": "Dystrophin\u2019s role in DGC links cytoskeleton to glycosylated sarcolemmal proteins.", "mechanism": "Novel DMD gene variants (missense) result in abnormal dystrophin, leading to dystrophinopathy phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887092" }, { "confidence": "medium", "disease": "Cardiomyopathy (in female carriers)", "glycan_involvement": "Glycosylation of DGC components may modulate cardiac muscle stability.", "mechanism": "Female carriers of DMD/BMD mutations have increased risk of cardiac involvement due to partial dystrophin deficiency.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC11887092" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Therapies seek to restore glycoprotein complex integrity at the sarcolemma.", "mechanism": "Restoration of dystrophin via gene therapy or exon-skipping aims to re-establish DGC function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887092" }, { "confidence": "medium", "disease": "Becker muscular dystrophy", "glycan_involvement": "Restored dystrophin supports glycosylated DGC structure.", "mechanism": "Precision medicine approaches target specific DMD mutations to improve dystrophin function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887092" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is part of the dystrophin-glycoprotein complex; glycosylation of associated proteins is critical for membrane stability.", "mechanism": "Loss of dystrophin leads to muscle membrane instability and progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887528" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of dystrophin-associated glycoproteins affects cardiac muscle integrity.", "mechanism": "Deficiency causes cardiac muscle fibrosis and dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887528" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "ACE is a glycoprotein; glycosylation affects its activity and stability.", "mechanism": "ACE inhibitors delay onset and progression of cardiomyopathy in DMD.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887528" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "AGTR1 is glycosylated; glycosylation modulates receptor function.", "mechanism": "ARBs block angiotensin II signaling, reducing cardiac fibrosis and dysfunction.", "protein": "Angiotensin II receptor type 1 (AGTR1)", "protein_enriched": { "function": "Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney (PubMed:15611106, PubMed:1567413, PubMed:25913193, PubMed:26", "gene_name": "AGTR1", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G12261QD", "G62765YT", "G84225JN" ], "uniprot_id": "P30556" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887528" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation influences receptor trafficking and signaling.", "mechanism": "Beta-blockers reduce cardiac workload and may delay progression.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887528" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation may affect receptor localization and function.", "mechanism": "MR antagonists may reduce cardiac fibrosis in DMD.", "protein": "Mineralocorticoid receptor", "protein_enriched": { "function": "Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target ", "gene_name": "NR3C2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08235" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887528" }, { "confidence": "low", "disease": "Cardiomyopathy", "glycan_involvement": "In vitro MRA activity may involve glycoprotein interactions.", "mechanism": "Vamorolone shows cardioprotective effects in preclinical models via MRA activity.", "protein": "Vamorolone", "relationship_type": "protective", "source_pmcid": "PMC11887528" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "SGLT2 is glycosylated; glycosylation affects transporter function.", "mechanism": "SGLT2 antagonists may delay cardiac failure in DMD.", "protein": "Sodium-glucose cotransporter 2 (SGLT2)", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1 (PubMed:20980548, PubMed:28592437, PubMed:34880493, Pu", "gene_name": "SLC5A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P31639" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11887528" }, { "confidence": "high", "disease": "Left ventricular dysfunction (LVD)", "glycan_involvement": "Glycosylation of dystrophin complex proteins is essential for cardiac muscle stability.", "mechanism": "Dystrophin deficiency leads to early myocardial damage and LVD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11887528" }, { "confidence": "high", "disease": "Left ventricular dysfunction (LVD)", "glycan_involvement": "Glycosylation may modulate ACE inhibitor efficacy.", "mechanism": "Prophylactic ACE inhibitor use delays onset of LVD and improves survival.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "protective", "source_pmcid": "PMC11887528" }, { "confidence": "medium", "disease": "Neurological disorders (e.g., epilepsy, neuropathic pain, spasticity)", "glycan_involvement": "N-glycosylation state (high-mannose vs. complex) modulates KCC2 maturation and surface expression.", "mechanism": "Altered glycosylation of KCC2 affects its trafficking, stability, and function in chloride homeostasis, impacting GABAergic inhibition.", "protein": "KCC2 (SLC12A5)", "protein_enriched": { "function": "K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou", "gene_name": "KCNK2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95069" }, "relationship_type": "causal", "source_pmcid": "PMC11894809" }, { "confidence": "high", "disease": "COPD-related sarcopenia", "glycan_involvement": "No direct glycosylation involvement for YAP/TAZ.", "mechanism": "Reduced YAP/TAZ promotes muscle aging and dysfunction; overexpression preserves muscle mass and function.", "protein": "YAP/TAZ", "relationship_type": "causal/protective", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "Skeletal muscle senescence", "glycan_involvement": "No direct glycosylation involvement for YAP/TAZ.", "mechanism": "YAP/TAZ maintain nuclear membrane integrity via ACTR2, reducing cytoplasmic dsDNA and STING activation.", "protein": "YAP/TAZ", "relationship_type": "protective", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "COPD-related sarcopenia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "ACTR2 supports nuclear lamina integrity; its expression is regulated by YAP/TAZ and is reduced in COPD muscle aging.", "protein": "ACTR2", "protein_enriched": { "function": "Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR", "gene_name": "Drd2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61168" }, "relationship_type": "protective", "source_pmcid": "PMC11905641" }, { "confidence": "medium", "disease": "Skeletal muscle senescence", "glycan_involvement": "STING is a glycoprotein; glycosylation may affect its trafficking and signaling.", "mechanism": "STING activation by cytoplasmic dsDNA drives muscle cell senescence in COPD.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "causal", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "COPD-related sarcopenia", "glycan_involvement": "Dystroglycan function depends on extensive O-glycosylation for ECM binding.", "mechanism": "Reduced dystroglycan expression marks muscle aging and dysfunction in COPD.", "protein": "dystroglycan", "relationship_type": "biomarker", "source_pmcid": "PMC11905641" }, { "confidence": "medium", "disease": "COPD-related sarcopenia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MYHC levels decrease in aged/atrophic muscle in COPD.", "protein": "MYHC", "protein_enriched": { "function": "Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotili", "gene_name": "MYH1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12882" }, "relationship_type": "biomarker", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "Skeletal muscle senescence", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "P21 upregulation marks cellular senescence in COPD muscle.", "protein": "P21", "protein_enriched": { "function": "Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA d", "gene_name": "CDKN1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P38936" }, "relationship_type": "biomarker", "source_pmcid": "PMC11905641" }, { "confidence": "medium", "disease": "Skeletal muscle senescence", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "\u03b3.H2AX marks DNA damage and senescence in muscle cells exposed to cigarette smoke.", "protein": "\u03b3.H2AX", "relationship_type": "biomarker", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "COPD-related sarcopenia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "YAP overexpression reverses muscle aging and dysfunction in COPD models.", "protein": "YAP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "COPD-related sarcopenia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "TAZ overexpression reverses muscle aging and dysfunction in COPD models.", "protein": "TAZ", "protein_enriched": { "function": "Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferati", "gene_name": "WWTR1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9GZV5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11905641" }, { "confidence": "high", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "O-mannosylation required for function; hypoglycosylation linked to disease.", "mechanism": "Upregulation correlates with motor improvement under nusinersen; essential for neuromuscular integrity.", "protein": "Alpha-dystroglycan (DAG1)", "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "high", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Initiates O-mannosylation pathway for DAG1 glycosylation.", "mechanism": "Upregulation correlates with clinical improvement; primes glycosylation of DAG1.", "protein": "Beta-1,4-glucuronyltransferase 1 (B4GAT1)", "protein_enriched": { "function": "", "gene_name": "TMEM256", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N2U0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "N-glycosylation affects receptor binding and axon growth inhibition.", "mechanism": "Downregulation associated with improved axogenesis and motor function.", "protein": "Oligodendrocyte Myelin Glycoprotein (OMG)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11909034" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Downregulation associated with reduced inhibition of axon regeneration.", "protein": "Reticulon-4 receptor (RTN4R)", "protein_enriched": { "function": "Receptor for RTN4, OMG and MAG (PubMed:12037567, PubMed:12068310, PubMed:12089450, PubMed:12426574, PubMed:12839991, PubMed:16712417, PubMed:18411262, PubMed:19052207). Functions as a receptor for the", "gene_name": "RTN4R", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G92551JA", "G62765YT", "G57321FI", "G43417UB", "G60667HJ" ], "uniprot_id": "Q9BZR6" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11909034" }, { "confidence": "high", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Glycosylation required for complement function.", "mechanism": "Downregulation correlates with motor improvement; reduced complement activation linked to better outcomes.", "protein": "Complement C4-A (C4A)", "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "high", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Glycosylation modulates activity.", "mechanism": "Downregulation correlates with improved motor function; less complement activation.", "protein": "Complement C1s (C1S)", "protein_enriched": { "function": "Component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogen", "gene_name": "C1S", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G48414YA", "G59626AS", "G84452RH", "G47737VJ", "G75983OB", "G94917XT", "G49108TO" ], "uniprot_id": "P09871" }, "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Glycosylation affects complement cascade.", "mechanism": "Downregulation correlates with clinical improvement; reduced neuroinflammation.", "protein": "Complement C7 (C7)", "protein_enriched": { "function": "Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane ", "gene_name": "C7", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G06110VR", "G15664MX", "G23719VF", "G24528MX", "G31852PQ", "G37399XV", "G41247ZX", "G41840AI", "G51653BI", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC", "G92406TI", "G61491DK", "G57321FI", "G29931IJ", "G43417UB", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G41071NU", "G43223CG", "G45395BF", "G47644PP", "G48414YA", "G57776ZS", "G61256FT", "G76295SF", "G79666IR", "G90382BL", "G90659AW" ], "uniprot_id": "P10643" }, "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "N-glycosylation critical for antibody function.", "mechanism": "Negative correlation with motor improvement; reduced humoral immune response in responders.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "medium", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Catalyzes glycan extension on DAG1.", "mechanism": "Differentiates responders from non-responders; involved in DAG1 glycosylation.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11909034" }, { "confidence": "low", "disease": "Spinal Muscular Atrophy (SMA)", "glycan_involvement": "Glycosylation affects Fc binding.", "mechanism": "Upregulated in responders; may reflect immune modulation.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11909034" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Dystrophin interacts with glycosylated DGC components; glycosylation is essential for complex stability.", "mechanism": "In-frame deletions in DMD gene lead to truncated dystrophin, causing BMD with variable severity.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "aSG is a glycoprotein; glycosylation required for membrane localization and function.", "mechanism": "Reduced but detectable aSG on sarcolemma in BMD mice; indicates partial DGC integrity.", "protein": "Alpha-sarcoglycan (aSG)", "protein_enriched": { "function": "Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation wi", "gene_name": "EPHB6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O15197" }, "relationship_type": "biomarker", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "nNOS localization depends on glycosylated DGC; glycosylation indirectly affects nNOS anchoring.", "mechanism": "Exon deletions remove nNOS-binding site on dystrophin, reducing sarcolemmal nNOS and leading to vascular dysfunction and muscle degeneration.", "protein": "Neuronal nitric oxide synthase (nNOS)", "relationship_type": "causal", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin interacts with glycosylated DGC components; glycosylation is required for function.", "mechanism": "Utrophin is upregulated in DMD and mdx mice, partially compensating for dystrophin loss.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Dystroglycan is heavily glycosylated; glycosylation is essential for ligand binding and DGC stability.", "mechanism": "Dystroglycan-binding site remains in truncated dystrophin in BMD, suggesting potential for therapies targeting glycosylation.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11913446" }, { "confidence": "medium", "disease": "Muscle degeneration", "glycan_involvement": "Glycosylation affects aSG stability and membrane localization.", "mechanism": "Reduced aSG correlates with muscle degeneration severity in BMD mice.", "protein": "Alpha-sarcoglycan (aSG)", "protein_enriched": { "function": "Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation wi", "gene_name": "EPHB6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O15197" }, "relationship_type": "biomarker", "source_pmcid": "PMC11913446" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Indirect; nNOS anchoring depends on glycosylated DGC.", "mechanism": "Reduced sarcolemmal nNOS leads to impaired vascular function and increased fibrosis.", "protein": "Neuronal nitric oxide synthase (nNOS)", "relationship_type": "causal", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Muscle degeneration", "glycan_involvement": "Dystrophin's interaction with glycosylated DGC is critical for membrane stability.", "mechanism": "Truncated dystrophin fails to protect sarcolemma, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11913446" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation is essential for dystroglycan's ECM interactions.", "mechanism": "Glycosylation status of dystroglycan affects fibrosis progression; potential target for therapy.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation required for aSG function and stability.", "mechanism": "aSG is absent or severely reduced in DMD, correlating with disease severity.", "protein": "Alpha-sarcoglycan (aSG)", "protein_enriched": { "function": "Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation wi", "gene_name": "EPHB6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O15197" }, "relationship_type": "biomarker", "source_pmcid": "PMC11913446" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Total CBG levels, not glycosylation per se.", "mechanism": "CBG deficiency independently predicts mortality at ICU admission.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "O-glycosylation (disialyl T) at Thr342 inhibits NE-mediated RCL cleavage, reducing cortisol release.", "mechanism": "Elevated RCL O-glycosylation at Thr342 correlates with increased disease severity.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "causal", "source_pmcid": "PMC11915215" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Glycosylation status may affect efficacy of CBG supplementation.", "mechanism": "CBG supplementation may improve cortisol delivery in septic shock.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "O-glycosylation (sialyl T/disialyl T) at RCL sites sterically hinders NE cleavage.", "mechanism": "RCL O-glycosylation at Thr342 and Thr345 inhibits NE-mediated proteolysis, modulating cortisol release.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "protective", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Quantitative increase in O-glycosylation at Thr342 in severe cases.", "mechanism": "Total RCL O-glycosylation level correlates with severity of septic shock.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11915215" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Steric hindrance by O-glycans inhibits NE cleavage.", "mechanism": "Elongated/branched O-glycans (disialyl T) at Thr342 may reduce cortisol release in severe septic shock.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "causal", "source_pmcid": "PMC11915215" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Co-existence of O-glycan at Thr342 and N-glycan at Asn347 observed in septic shock sera.", "mechanism": "RCL N- and O-glycan co-occupancy may be altered in septic shock.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11915215" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Changes in N- and O-glycosylation patterns.", "mechanism": "Aberrant glycosylation of CBG and other serum proteins reported in sepsis.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "O-glycosylation at Thr342 inhibits proteolysis and cortisol release.", "mechanism": "Reduced NE-mediated RCL cleavage due to increased O-glycosylation may impair anti-inflammatory cortisol delivery.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "causal", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Site-specific O-glycosylation (Thr342) detected by LC\u2013MS/MS.", "mechanism": "RCL O-glycosylation at Thr342 is more prevalent in septic shock than in healthy controls.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11915215" }, { "confidence": "high", "disease": "Autoimmune disorders", "glycan_involvement": "N-glycosylation of IgG modulates immune effector functions.", "mechanism": "Altered glycosylation of IgG leads to changes in structure, secretion, and immune function, promoting autoimmunity.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "Altered N-glycosylation patterns in IgG.", "mechanism": "Changes in IgG glycosylation associated with B cell hyperactivation and autoimmunity in dystonia.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "Binds to exposed glycans on damaged organelles.", "mechanism": "Galectin-3 senses damage-exposed glycans and coordinates lysosomal repair, impacting autophagy in dystonia.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "ER stress from misfolded glycoproteins activates EIF2\u03b1.", "mechanism": "Aberrant activation in response to ER stress and unfolded glycoproteins contributes to neuronal dysfunction.", "protein": "EIF2\u03b1 (eukaryotic initiation factor 2 alpha)", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Glycosylation of CD22 regulates B cell signaling and tolerance; altered glycosylation promotes autoimmunity.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "Sialylated glycans required for Siglec-G function.", "mechanism": "Glycosylation-dependent recognition of ligands modulates B cell activation and autoimmunity.", "protein": "Siglec-G", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "Glycoprotein modifications required for cytoskeletal function.", "mechanism": "Defective glycosylation impairs cytoskeletal protein conformation and ECM attachment, contributing to dystonia.", "protein": "Cytoskeletal proteins", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "N- and O-glycosylation in ER/Golgi required for secretion.", "mechanism": "ER stress and defective glycosylation lead to functionally deficient secreted proteins in genetic dystonia.", "protein": "Secreted proteins (ER/Golgi processed)", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "O-GlcNAcylation as a post-translational modification.", "mechanism": "O-GlcNAcylation of histones affects chromatin structure and gene expression, contributing to dystonia pathogenesis.", "protein": "Histones", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Defective N- and O-glycosylation pathways.", "mechanism": "Mutations in glycosylation enzymes cause CDG, leading to neurological symptoms including dystonia.", "protein": "Glycosylation enzymes", "relationship_type": "causal", "source_pmcid": "PMC11920444" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy R14 (LGMDR14)", "glycan_involvement": "Defective O-mannosylation of \u03b1-DG", "mechanism": "POMT2 variants impair O-mannosylation of \u03b1-dystroglycan, leading to reduced \u03b1-DG glycosylation and muscle pathology.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Severely impaired O-mannosylation of \u03b1-DG", "mechanism": "Severe POMT2 loss-of-function variants cause profound \u03b1-DG hypoglycosylation, resulting in WWS with brain and eye involvement.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Congenital muscular dystrophy (CMD)", "glycan_involvement": "Impaired O-mannosylation of \u03b1-DG", "mechanism": "POMT2 mutations reduce \u03b1-DG glycosylation, causing CMD with variable severity.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathies (\u03b1-DGPs)", "glycan_involvement": "O-mannosylation required for functional glycan epitopes", "mechanism": "Hypoglycosylation of \u03b1-DG disrupts its binding to extracellular matrix proteins, leading to muscular dystrophy and brain/eye defects.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Cobblestone lissencephaly", "glycan_involvement": "Loss of O-mannosyl glycan disrupts laminin binding", "mechanism": "Defective glycosylation of \u03b1-DG impairs neuronal migration, causing brain malformations.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Retinal abnormalities/visual impairment", "glycan_involvement": "O-mannosylation essential for retinal tissue integrity", "mechanism": "Hypoglycosylated \u03b1-DG fails to maintain retinal structure, leading to visual impairment.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "O-mannosylation required for cardiac muscle function", "mechanism": "Reduced \u03b1-DG glycosylation affects cardiac muscle stability, predisposing to cardiomyopathy.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "O-mannosylation needed for neuronal migration and function", "mechanism": "Impaired \u03b1-DG glycosylation affects neuronal function, contributing to cognitive deficits.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathies (\u03b1-DGPs)", "glycan_involvement": "Initiates O-mannosylation of \u03b1-DG", "mechanism": "POMT2 mutations disrupt the initial step of O-mannosylation in \u03b1-DG, underlying the spectrum of \u03b1-DGPs.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Cobblestone lissencephaly", "glycan_involvement": "Loss of O-mannosylation on \u03b1-DG", "mechanism": "POMT2 splicing variants (e.g., c.1006+1G>A) cause truncated protein, leading to \u03b1-DG hypoglycosylation and neuronal migration defects.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC11921505" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Regulates ER-localized glycosylation enzymes; loss leads to abnormal glycoprotein processing.", "mechanism": "Downregulation in synovial tissue correlates with loss of glycosylation, ER stress, and impaired tissue repair.", "protein": "TMEM230", "protein_enriched": { "function": "Probable serine lipid hydrolase associated with lipid droplets (By similarity). Has low cholesterol esterase activity (By similarity). Appears to lack triglyceride lipase activity (By similarity). Inv", "gene_name": "LDAH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6V9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11942208" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Involved in turnover of glycosylated antibodies and antigen processing.", "mechanism": "Downregulation impairs lysosomal recycling and antibody glycosylation, contributing to autoimmunity.", "protein": "RNASET2", "protein_enriched": { "function": "Exhibits a potent RNase activity (PubMed:12244054, PubMed:12527768, PubMed:17150966). Has broad-spectrum antimicrobial activity against many pathogenic microorganisms including uropathogenic E.coli (U", "gene_name": "RNASE7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H1E1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11942208" }, { "confidence": "high", "disease": "Parkinson's disease (PD)", "glycan_involvement": "ER-dependent glycosylation critical for protein folding; loss leads to Lewy body formation.", "mechanism": "Mutations cause ER protein misfolding, defective glycosylation, and neuronal death.", "protein": "TMEM230", "protein_enriched": { "function": "Probable serine lipid hydrolase associated with lipid droplets (By similarity). Has low cholesterol esterase activity (By similarity). Appears to lack triglyceride lipase activity (By similarity). Inv", "gene_name": "LDAH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6V9" }, "relationship_type": "causal", "source_pmcid": "PMC11942208" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation defects impair protein folding and clearance.", "mechanism": "Mutations disrupt ER protein quality control and glycosylation, promoting amyloid aggregation.", "protein": "TMEM230", "protein_enriched": { "function": "Probable serine lipid hydrolase associated with lipid droplets (By similarity). Has low cholesterol esterase activity (By similarity). Appears to lack triglyceride lipase activity (By similarity). Inv", "gene_name": "LDAH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6V9" }, "relationship_type": "causal", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Regulates glycosylation of cell adhesion molecules and angiogenic factors.", "mechanism": "Misexpression promotes aberrant angiogenesis and tissue remodeling via glycosylation changes.", "protein": "TMEM230", "protein_enriched": { "function": "Probable serine lipid hydrolase associated with lipid droplets (By similarity). Has low cholesterol esterase activity (By similarity). Appears to lack triglyceride lipase activity (By similarity). Inv", "gene_name": "LDAH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6V9" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Aging/Autoimmune disorders", "glycan_involvement": "Glycosylated extracellular domains mediate cell-cell signaling.", "mechanism": "Glycosylation status modulates cell fate and immune interactions; altered in aging and autoimmunity.", "protein": "Notch receptor family", "relationship_type": "causal", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosaminoglycan chains modulate synovial fluid properties.", "mechanism": "Altered glycosylation affects joint lubrication and immune tolerance.", "protein": "PRG4 (lubricin)", "relationship_type": "biomarker", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Downregulation and glycosylation changes impact tissue repair and inflammation.", "protein": "POSTN (periostin)", "protein_enriched": { "function": "Induces cell attachment and spreading and plays a role in cell adhesion (PubMed:12235007). Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic ac", "gene_name": "POSTN", "glycan_count": 160, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02030ZB", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G05049YU", "G05724UK", "G06110VR", "G06356OH", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G11870QZ", "G12313PD", "G12341GU", "G13131HA", "G14669DU", "G14972EH", "G14994KB", "G17208MA", "G18647XP", "G20210JR", "G20706XG", "G23294PN", "G23453IV", "G23505EP", "G23719VF", "G23863VK", "G24835MQ", "G25418HZ", "G25451PN", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G31916IQ", "G33609NS", "G34989PA", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G45504EY", "G46524LG", "G46687AB", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G47702MW", "G47950XN", "G48414YA", "G49874UX", "G49955PK", "G50045TK", "G50757KG", "G51640FO", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G64409MC", "G64527OM", "G65019XG", "G65092SV", "G65184UU", "G66621EA", "G66760KM", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G72291OX", "G72398FA", "G72667IM", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G74430RZ", "G74724QE", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80920RR", "G81198YO", "G81263BG", "G81295CK", "G82119TF", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G84820NF", "G86182NS", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G88891KO", "G90382BL", "G90659AW", "G90734RJ", "G91636VS", "G92050GC", "G92062TF", "G92135MA", "G92275SC", "G92406TI", "G94470IW", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G96430BV", "G98611JV", "G57321FI", "G49108TO" ], "uniprot_id": "Q15063" }, "relationship_type": "biomarker", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Autoimmune disorders (general)", "glycan_involvement": "Fc glycan modifications regulate antibody activity.", "mechanism": "Aberrant glycosylation leads to altered immune effector functions and self-reactivity.", "protein": "Antibodies (IgG)", "relationship_type": "causal", "source_pmcid": "PMC11942208" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Enzymatic control of N- and O-glycosylation on multiple proteins.", "mechanism": "Downregulation impairs glycan synthesis, affecting cell-cell recognition and immune tolerance.", "protein": "Glycosyl transferases", "relationship_type": "causal", "source_pmcid": "PMC11942208" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Loss of CS/KS glycosylation impairs hydration and resilience.", "mechanism": "Aggrecan degradation by MMPs and ADAMTS leads to loss of cartilage biomechanical properties.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "causal", "source_pmcid": "PMC11942259" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "High-sulfation KS chains detected in tumors.", "mechanism": "Upregulated in glioblastoma; sulfation status of KS chains differs between normal and tumor cells.", "protein": "Podocalyxcin", "protein_enriched": { "function": "Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot proces", "gene_name": "PODXL", "glycan_count": 64, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G63041LO", "G70101JE", "G80920RR", "G57321FI", "G23125GY", "G53434XO", "G58001LT", "G29068FM", "G43417UB", "G57317CE", "G73004SD", "G88713AC", "G49108TO", "G00273SJ", "G00912UN", "G03382KH", "G04657PL", "G06247RL", "G08918WF", "G10773YW", "G10846ZT", "G20210JR", "G23863VK", "G23984SE", "G25451PN", "G27058EU", "G27126ED", "G27947YN", "G34029GR", "G40574BA", "G40834TG", "G43669FQ", "G45395BF", "G45883VE", "G46691LC", "G47012YE", "G47644PP", "G47702MW", "G48414YA", "G51640FO", "G53075ES", "G57776ZS", "G59626AS", "G60177UT", "G62894KT", "G70232NH", "G75568BH", "G75983OB", "G77669RF", "G79666IR", "G80075MS", "G80223IX", "G82119TF", "G83229XP", "G84452RH", "G84820NF", "G86880BF", "G87123QX", "G90659AW", "G91473PK", "G92062TF", "G92135MA", "G98611JV" ], "uniprot_id": "O00592" }, "relationship_type": "biomarker", "source_pmcid": "PMC11942259" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "KS chains regulate neurotransmitter storage/release.", "mechanism": "Abnormal SV2-mediated neurotransmitter release implicated in epilepsy.", "protein": "SV2", "relationship_type": "causal", "source_pmcid": "PMC11942259" }, { "confidence": "medium", "disease": "Polymyositis", "glycan_involvement": "Low-sulfation KS chains present.", "mechanism": "PRELP deposited at myofibers surrounded by inflammatory cells in polymyositis.", "protein": "PRELP", "relationship_type": "biomarker", "source_pmcid": "PMC11942259" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "HS-PG interactions mediate synaptic plasticity.", "mechanism": "Neurexin dysfunction affects synaptic stabilization and neural network specificity.", "protein": "Neurexins", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11942259" }, { "confidence": "high", "disease": "Congenital Myasthenic Syndromes", "glycan_involvement": "HS chains mediate receptor clustering.", "mechanism": "Disrupted agrin-LRP4-MuSK signaling impairs NMJ formation.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC11942259" }, { "confidence": "high", "disease": "Astrocytoma", "glycan_involvement": "High-sulfation KS chains in tumor cells.", "mechanism": "Upregulated in astrocytoma; KS chain sulfation status is altered.", "protein": "Podocalyxcin", "protein_enriched": { "function": "Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot proces", "gene_name": "PODXL", "glycan_count": 64, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G63041LO", "G70101JE", "G80920RR", "G57321FI", "G23125GY", "G53434XO", "G58001LT", "G29068FM", "G43417UB", "G57317CE", "G73004SD", "G88713AC", "G49108TO", "G00273SJ", "G00912UN", "G03382KH", "G04657PL", "G06247RL", "G08918WF", "G10773YW", "G10846ZT", "G20210JR", "G23863VK", "G23984SE", "G25451PN", "G27058EU", "G27126ED", "G27947YN", "G34029GR", "G40574BA", "G40834TG", "G43669FQ", "G45395BF", "G45883VE", "G46691LC", "G47012YE", "G47644PP", "G47702MW", "G48414YA", "G51640FO", "G53075ES", "G57776ZS", "G59626AS", "G60177UT", "G62894KT", "G70232NH", "G75568BH", "G75983OB", "G77669RF", "G79666IR", "G80075MS", "G80223IX", "G82119TF", "G83229XP", "G84452RH", "G84820NF", "G86880BF", "G87123QX", "G90659AW", "G91473PK", "G92062TF", "G92135MA", "G98611JV" ], "uniprot_id": "O00592" }, "relationship_type": "biomarker", "source_pmcid": "PMC11942259" }, { "confidence": "medium", "disease": "Pancreatic Cancer", "glycan_involvement": "KS chains modulate ECM interactions.", "mechanism": "Lumican impedes tumor growth via MMP inhibition and integrin interactions.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11942259" }, { "confidence": "high", "disease": "Retinitis Pigmentosa", "glycan_involvement": "O-mannosyl glycan interactions with \u03b1-DG stabilize synapse.", "mechanism": "Mutations in Eyes-Shut disrupt photoreceptor ribbon synapse, impairing vision.", "protein": "Eyes-Shut", "relationship_type": "causal", "source_pmcid": "PMC11942259" }, { "confidence": "low", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation status may regulate energy homeostasis.", "mechanism": "Osteoglycin linked to insulin resistance and metabolic disorders.", "protein": "Osteoglycin", "relationship_type": "biomarker", "source_pmcid": "PMC11942259" }, { "confidence": "high", "disease": "Ageing", "glycan_involvement": "Loss of mucin-type O-glycosylation reduces glycocalyx integrity.", "mechanism": "Downregulation leads to impaired BBB function and increased permeability.", "protein": "Mucin-domain glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Decreased mucin-type O-glycosylation on endothelium.", "mechanism": "Reduced expression and O-glycosylation associated with BBB dysfunction.", "protein": "Mucin-domain glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Ageing", "glycan_involvement": "Reduced core 1 O-glycosylation on mucin-domain glycoproteins.", "mechanism": "Downregulation impairs core 1 O-glycan synthesis, compromising BBB.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Loss of core 1 O-glycosylation.", "mechanism": "Downregulation in AD brains correlates with BBB dysfunction.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Ageing", "glycan_involvement": "Reduced O-glycan extension on mucin-domain glycoproteins.", "mechanism": "Downregulation reduces extended core 1 O-glycan synthesis, affecting BBB.", "protein": "B3GNT3", "protein_enriched": { "function": "Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference fo", "gene_name": "B3GNT2", "glycan_count": 25, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G62765YT", "G80920RR", "G83460ZZ", "G85282JO", "G56784JY", "G27058EU", "G82348BZ", "G83633GK", "G22573RC", "G22768VO", "G25418HZ", "G31852PQ", "G42227JK", "G70101JE", "G81315DD", "G06356OH", "G33791AF", "G48414YA", "G86795LJ", "G57321FI", "G04854VP", "G63980BQ", "G75983OB", "G94470IW" ], "uniprot_id": "Q9NY97" }, "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Reduced O-glycan extension.", "mechanism": "Downregulation in AD brains linked to BBB dysfunction.", "protein": "B3GNT3", "protein_enriched": { "function": "Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference fo", "gene_name": "B3GNT2", "glycan_count": 25, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G62765YT", "G80920RR", "G83460ZZ", "G85282JO", "G56784JY", "G27058EU", "G82348BZ", "G83633GK", "G22573RC", "G22768VO", "G25418HZ", "G31852PQ", "G42227JK", "G70101JE", "G81315DD", "G06356OH", "G33791AF", "G48414YA", "G86795LJ", "G57321FI", "G04854VP", "G63980BQ", "G75983OB", "G94470IW" ], "uniprot_id": "Q9NY97" }, "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Cerebral haemorrhage", "glycan_involvement": "Loss of O-glycosylated mucin domains destabilizes vasculature.", "mechanism": "Acute enzymatic removal leads to brain bleeding in mice.", "protein": "Mucin-domain glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Reduced O-glycosylation weakens barrier.", "mechanism": "Loss increases BBB leakiness, allowing neurotoxic factors to enter brain.", "protein": "Mucin-domain glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Cognitive impairment", "glycan_involvement": "Enhanced O-glycan extension on mucin-domain glycoproteins.", "mechanism": "Overexpression restores O-glycosylation, improves cognition in aged mice.", "protein": "B3GNT3", "protein_enriched": { "function": "Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference fo", "gene_name": "B3GNT2", "glycan_count": 25, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G62765YT", "G80920RR", "G83460ZZ", "G85282JO", "G56784JY", "G27058EU", "G82348BZ", "G83633GK", "G22573RC", "G22768VO", "G25418HZ", "G31852PQ", "G42227JK", "G70101JE", "G81315DD", "G06356OH", "G33791AF", "G48414YA", "G86795LJ", "G57321FI", "G04854VP", "G63980BQ", "G75983OB", "G94470IW" ], "uniprot_id": "Q9NY97" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11946907" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "Restores core 1 O-glycosylation.", "mechanism": "Overexpression partially restores BBB function and reduces neuroinflammation.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11946907" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is glycosylated; glycosylation affects membrane localization and stability.", "mechanism": "Mutations in dystrophin gene cause loss of functional dystrophin, leading to muscle membrane instability and DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates utrophin's membrane association.", "mechanism": "Upregulation of utrophin can partially compensate for dystrophin deficiency in DMD.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11948207" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "CK is glycosylated; glycosylation may affect serum stability.", "mechanism": "Elevated CK in serum indicates muscle breakdown in DMD and rhabdomyolysis.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Cardiac involvement in DMD", "glycan_involvement": "CK-MB glycosylation may influence cardiac release kinetics.", "mechanism": "Elevated CK-MB reflects cardiac muscle damage in DMD.", "protein": "Creatine kinase-MB (CK-MB)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with larg", "gene_name": "CKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06732" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Myoglobin is glycosylated; glycosylation affects renal clearance.", "mechanism": "Serum myoglobin increases with muscle injury in DMD.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "LDH glycosylation may affect serum half-life.", "mechanism": "Elevated LDH is a marker of muscle and tissue damage in DMD.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "AST glycosylation influences serum stability.", "mechanism": "AST is released from damaged muscle in DMD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "ALT glycosylation affects serum detection.", "mechanism": "ALT is elevated in muscle injury and DMD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Oxidative stress-related diseases", "glycan_involvement": "Glycosylation may regulate enzyme activity and stability.", "mechanism": "NRF2 activation increases glutathione synthase, enhancing antioxidant defense in DMD and other oxidative stress diseases.", "protein": "Glutathione synthase", "protein_enriched": { "function": "Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner (PubMed:7646467, PubMed:9215686). Glutathione (gamma-glutamylcysteinylglycine, GSH) is the mo", "gene_name": "GSS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48637" }, "relationship_type": "protective", "source_pmcid": "PMC11948207" }, { "confidence": "medium", "disease": "Hepatic toxicity", "glycan_involvement": "GGT glycosylation affects enzymatic activity and serum levels.", "mechanism": "GGT is monitored to assess liver toxicity during DMD therapy.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11948207" }, { "confidence": "high", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "CA125 is a heavily O-glycosylated mucin; glycosylation is essential for its antigenicity and secretion.", "mechanism": "Elevated serum CA125 reflects inflammation, fluid overload, and myocardial remodeling in CHF.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation enables CA125 release from mesothelial cells under mechanical/inflammatory stress.", "mechanism": "High CA125 levels strongly predict mortality in HFpEF, possibly via association with diastolic dysfunction and left atrial enlargement.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "O-glycosylation is required for CA125's stability and detection in serum.", "mechanism": "Elevated CA125 is associated with increased mortality in HFrEF, reflecting disease severity.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Heart Failure with Mid-range Ejection Fraction (HFmrEF)", "glycan_involvement": "Glycosylation is necessary for CA125's function as a circulating biomarker.", "mechanism": "High CA125 levels are linked to increased mortality in HFmrEF.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Mucin-type O-glycosylation creates the CA125 epitope recognized in diagnostics.", "mechanism": "CA125 is a classical tumor marker for ovarian cancer.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Pericardial Effusion", "glycan_involvement": "Glycosylation facilitates CA125 secretion during serosal inflammation.", "mechanism": "CA125 is elevated in pericardial effusion due to mesothelial cell activation.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Pleural Effusion", "glycan_involvement": "Glycosylation is essential for CA125's release and detection.", "mechanism": "CA125 is increased in pleural effusion, reflecting mesothelial cell response to fluid overload.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Peritonitis", "glycan_involvement": "O-glycosylation supports CA125's antigenic properties.", "mechanism": "CA125 is elevated in peritonitis due to inflammation of the peritoneal lining.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "Glycosylation enables CA125's stability in circulation.", "mechanism": "CA125 is increased in liver cirrhosis, possibly due to serosal inflammation and fluid accumulation.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Glycosylation is required for CA125's secretion and function.", "mechanism": "CA125 correlates with pulmonary hypertension severity in CHF patients.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11948815" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates ECM interactions and stability.", "mechanism": "Regulates collagen assembly and fibroblast function; consistently elevated across HF stages.", "protein": "Thrombospondin-2 (TSP2)", "protein_enriched": { "function": "Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties", "gene_name": "THBS2", "glycan_count": 76, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02886BB", "G06356OH", "G07755XJ", "G10486CT", "G23432EQ", "G25418HZ", "G27058EU", "G27947YN", "G31852PQ", "G37412TK", "G40926MX", "G42124LM", "G43769HG", "G44215PV", "G45504EY", "G46902YN", "G48414YA", "G50045TK", "G57776ZU", "G59626AS", "G60033FS", "G61256FT", "G62765YT", "G65092SV", "G65184UU", "G70101JE", "G72398FA", "G72787SB", "G72790NZ", "G76295SF", "G80223IX", "G80920RR", "G81295CK", "G83460ZZ", "G83633GK", "G83646BJ", "G86182NS", "G90659AW", "G06110VR", "G57321FI", "G01650EU", "G02815KT", "G05049YU", "G11314AS", "G23863VK", "G28541PG", "G41071NU", "G47644PP", "G70441OD", "G79666IR", "G80479JV", "G92406TI", "G95865ZB", "G04657PL", "G11629QQ", "G23453IV", "G27126ED", "G28681TP", "G29880MM", "G33416PL", "G33609NS", "G36379GD", "G39446WN", "G41247ZX", "G45395BF", "G46691LC", "G51640FO", "G57317CE", "G72735IY", "G80075MS", "G81263BG", "G82119TF", "G84452RH", "G92050GC" ], "uniprot_id": "P35442" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation affects secretion and ECM binding.", "mechanism": "Promotes fibroblast activation and ECM deposition; upregulated in activated fibroblast subpopulations.", "protein": "Periostin (POSTN)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation influences cell-matrix interactions.", "mechanism": "Induced during injury; marks activated fibroblast subpopulations and ECM remodeling.", "protein": "Tenascin C (TNC)", "protein_enriched": { "function": "Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cort", "gene_name": "TNC", "glycan_count": 202, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G14669DU", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G40574BA", "G41247ZX", "G41840AI", "G48414YA", "G49018RC", "G55220VL", "G59626AS", "G59924QI", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G70619PT", "G72291OX", "G73430PD", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G82830MN", "G90382BL", "G92050GC", "G92406TI", "G95865ZB", "G98611JV", "G01485JJ", "G05049YU", "G07755XJ", "G08290VR", "G10773YW", "G11314AS", "G14972EH", "G18647XP", "G20312EM", "G23719VF", "G25418HZ", "G27058EU", "G34989PA", "G36379GD", "G41071NU", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G46691LC", "G47644PP", "G57776ZU", "G63041LO", "G70441OD", "G73968GN", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G84349RE", "G84452RH", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G92275SC", "G95177YH", "G49108TO", "G11629QQ", "G15169WU", "G22310AV", "G40834TG", "G56784JY", "G57776ZS", "G70232NH", "G04657PL", "G07246CJ", "G15664MX", "G20706XG", "G27126ED", "G30221QT", "G43669FQ", "G45495MK", "G45526EA", "G59324HL", "G77582RK", "G77669RF", "G80075MS", "G80479JV", "G81637OR", "G82443XX", "G84225JN", "G87123QX", "G08146BT", "G23863VK", "G37868ZX", "G37881RL", "G51413EV", "G57818FI", "G68490OW", "G71146HJ", "G93718GY", "G43417UB", "G05962QB", "G12341GU", "G34617SM", "G35541EV", "G39471UU", "G53075ES", "G79286RS", "G96577RX", "G10819WX", "G17208MA", "G20528HD", "G23010ZW", "G27915IV", "G27947YN", "G29545VG", "G30740WO", "G31916IQ", "G33791AF", "G38663NM", "G42962KI", "G46687AB", "G47012YE", "G47518TP", "G52890YB", "G60834IK", "G61937QU", "G64394MX", "G69521XL", "G72797UR", "G80223IX", "G81263BG", "G91473PK", "G39595FH", "G63980BQ", "G94470IW", "G01160VV", "G16125XL", "G23505EP", "G25451PN", "G30970QQ", "G31986NC", "G32788FZ", "G33416PL", "G37692EO", "G40206WX", "G44753VC", "G50856PC", "G55132BD", "G56770VP", "G60033FS", "G62894KT", "G65092SV", "G67164EE", "G72197KC", "G72747WU", "G78649WQ", "G89045VA", "G90093AU", "G60177UT", "G70894RY", "G83229XP", "G95133RI", "G02528FI", "G10488MI", "G11870QZ", "G25079LO", "G37509XX", "G37995HC", "G40926MX", "G57317CE", "G72787SB", "G72790NZ", "G84862VB", "G92551JA", "G86182NS", "G36442WJ", "G37412TK", "G45504EY", "G46503DX", "G49755GI", "G51653BI", "G54612UD", "G58954YZ", "G83646BJ", "G85282JO", "G85554PZ" ], "uniprot_id": "P24821" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates stability and receptor interactions.", "mechanism": "Elevated in advanced HF; correlates with increased TGF-\u03b2 signaling and fibrosis severity.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects ECM assembly.", "mechanism": "Associated with ECM organization and fibrosis; elevated in HF and correlates with cardiac dysfunction.", "protein": "MFAP4", "protein_enriched": { "function": "May play a role in hematopoiesis. In the cardiovascular system, could regulate growth factors or participate in cell signaling in maintaining large vessel integrity (By similarity). Component of the e", "gene_name": "MFAP5", "glycan_count": 36, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G29931IJ", "G43417UB", "G00912UN", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G08918WF", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G34989PA", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G46691LC", "G47644PP", "G51640FO", "G57776ZS", "G58954YZ", "G59626AS", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G73968GN", "G76295SF", "G79666IR", "G84452RH", "G86182NS", "G90382BL", "G90659AW" ], "uniprot_id": "Q13361" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates cell adhesion properties.", "mechanism": "Causally linked to HF risk and LV structure; involved in cell adhesion and ECM organization.", "protein": "SVEP1", "protein_enriched": { "function": "Receptor that may have an important role in cell/cell signaling during nervous system formation", "gene_name": "CELSR2", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G41071NU", "G00912UN", "G25451PN", "G27058EU", "G40834TG", "G45395BF", "G48414YA", "G80920RR", "G49108TO", "G04657PL", "G34617SM", "G79666IR", "G87123QX", "G75983OB", "G48584BU", "G64527OM", "G70101JE", "G70822IO", "G02815KT", "G45504EY", "G06110VR", "G31852PQ", "G65184UU", "G43417UB", "G05049YU", "G83460ZZ", "G57321FI", "G62765YT" ], "uniprot_id": "Q9HCU4" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation influences ECM interactions.", "mechanism": "Causally associated with HF risk; regulates ECM and cell adhesion.", "protein": "SPON1", "protein_enriched": { "function": "Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro. May contribute to the growth and guidance of axons in both the spinal", "gene_name": "SPON1", "glycan_count": 26, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G27058EU", "G28541PG", "G37399XV", "G39446WN", "G41247ZX", "G59626AS", "G59924QI", "G62765YT", "G65184UU", "G72291OX", "G72398FA", "G80920RR", "G82463GQ", "G90659AW", "G95865ZB", "G61491DK" ], "uniprot_id": "Q9HCB6" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Associated with fibrotic remodeling and HF risk.", "protein": "FSTL3", "protein_enriched": { "function": "Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such as activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellula", "gene_name": "FSTL3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G43769HG" ], "uniprot_id": "O95633" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Glycosylation modulates cell migration and signaling.", "mechanism": "Knockdown reduces fibroblast proliferation and soluble ST2 levels; protective against fibrosis.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11949229" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation influences ECM binding and function.", "mechanism": "Associated with fibrosis, inflammation, and aging-related cardiovascular decline.", "protein": "TGFBI", "protein_enriched": { "function": "Plays a role in cell adhesion (PubMed:8024701). May play a role in cell-collagen interactions (By similarity)", "gene_name": "TGFBI", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q15582" }, "relationship_type": "biomarker", "source_pmcid": "PMC11949229" }, { "confidence": "high", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "Changes in fucosylation, bisecting GlcNAc, sialylation, and galactosylation of IgG N-glycans are associated with disease severity and outcome.", "mechanism": "Altered IgG N-glycome composition (notably GP4) at ICU admission predicts in-hospital mortality risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11955649" }, { "confidence": "high", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "GP4 (fucosylated 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"confidence": "medium", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "Lower fucosylation leads to increased immune activation and inflammation.", "mechanism": "Decreased fucosylation increases IgG's ability to trigger ADCC via Fc\u03b3RIIIa, enhancing inflammatory cytokine release.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11955649" }, { "confidence": "medium", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "Galactosylation status reflects acute inflammation and disease severity.", "mechanism": "Altered galactosylation (higher agalactosylated, lower mono- and digalactosylated glycans) is associated with sepsis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11955649" }, { "confidence": "medium", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "Bisecting GlcNAc modification may modulate IgG effector functions.", "mechanism": "Increased bisecting GlcNAc in IgG N-glycans is observed in sepsis patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11955649" }, { "confidence": "medium", "disease": "Escherichia coli-induced sepsis", "glycan_involvement": "Sialylation modulates anti-inflammatory activity of IgG.", "mechanism": "Lower sialylation of IgG N-glycans is associated with sepsis and poor outcome.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11955649" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "Altered N-glycosylation affects inflammatory pathways.", "mechanism": "IgG N-glycan changes are involved in pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11955649" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates immune response and tumor progression.", "mechanism": "IgG N-glycan changes contribute to disease mechanisms.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11955649" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "Altered glycosylation affects antibody effector functions.", "mechanism": "IgG N-glycan changes are implicated in disease pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11955649" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Contains N-linked glycosylation sites important for function and expression.", "mechanism": "Overexpressed in anti-inflammatory microglia within glioma lesions; visualized by PET imaging.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11959882" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation may regulate receptor localization and stability.", "mechanism": "Upregulated in anti-inflammatory microglia during acute phase of epilepsy; PET signal correlates with lesion activity.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11959882" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation likely affects microglial receptor function.", "mechanism": "Reported as a promising biomarker due to phenotype-dependent expression in microglia.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11959882" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for proper receptor folding and surface expression.", "mechanism": "Expression increases in anti-inflammatory microglia during neuroinflammatory responses; visualized by PET.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11959882" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "N-glycosylation status may change with age, affecting receptor levels.", "mechanism": "Expression reduced in aging brain; lower PET tracer uptake reflects decreased anti-inflammatory microglia.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11959882" }, { "confidence": "high", "disease": "Alzheimer disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation is essential for its synaptic vesicle localization and function.", "mechanism": "Reduced SV2A density (measured by [18F]SynVesT-1 PET) reflects synaptic loss, correlating with AD pathology (amyloid \u03b2 and tau accumulation).", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation may stabilize SV2A and maintain synaptic function.", "mechanism": "Preserved SV2A density is associated with resilience to neurodegeneration and better cognitive performance despite brain atrophy.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "protective", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Amnestic mild cognitive impairment", "glycan_involvement": "Glycosylation status may affect SV2A stability and synaptic localization.", "mechanism": "Lower SV2A density detected in patients, indicating early synaptic dysfunction.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Nonamnestic mild cognitive impairment", "glycan_involvement": "Glycosylation is required for SV2A function.", "mechanism": "Reduced SV2A PET signal observed, reflecting synaptic loss.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Posterior cortical atrophy", "glycan_involvement": "Glycosylation may influence SV2A's role in synaptic maintenance.", "mechanism": "Regional reduction in SV2A PET signal mirrors tau pathology and synaptic degeneration.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Logopenic variant primary progressive aphasia", "glycan_involvement": "Glycosylation is important for SV2A trafficking and function.", "mechanism": "Decreased SV2A PET uptake in affected cortical regions corresponds to disease phenotype.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "low", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation may affect drug binding and SV2A function.", "mechanism": "SV2A is targeted by antiepileptic drugs; modulation may affect synaptic function in AD.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11960604" }, { "confidence": "high", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation is necessary for SV2A's synaptic role.", "mechanism": "Inverse correlation between SV2A PET signal and amyloid \u03b2/tau PET signal; SV2A loss tracks with pathological protein accumulation.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation may modulate SV2A's stability and PET detectability.", "mechanism": "SV2A PET signal provides additive information to MRI atrophy markers for predicting cognitive impairment.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation maintains SV2A function across lifespan.", "mechanism": "No significant age-related decline in SV2A PET signal in controls, supporting disease specificity.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11960604" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "O-glycosylation of Ser/Thr residues; changes affect barrier function.", "mechanism": "Altered MUC2 glycosylation or reduced thickness compromises mucus barrier, increasing inflammation.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "O-glycosylation pattern changes; affects mucosal protection.", "mechanism": "Altered MUC2 glycosylation and mucus properties linked to increased cancer risk.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Type II Diabetes", "glycan_involvement": "O-glycosylation changes impact gut barrier and microbiota.", "mechanism": "Perturbed MUC2 glycosylation and mucus composition associated with metabolic dysfunction.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation modulates barrier and microbial interactions.", "mechanism": "Altered mucus thickness and glycosylation linked to obesity-related gut barrier changes.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "low", "disease": "Cardiovascular Diseases", "glycan_involvement": "O-glycosylation affects systemic inflammation via gut barrier.", "mechanism": "Mucus perturbation and glycosylation changes associated with cardiovascular risk.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "high", "disease": "Gut Dysbiosis", "glycan_involvement": "O-glycosylation determines bacterial access to mucin.", "mechanism": "Altered glycosylation changes microbial colonization and composition.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Selective cleavage of O-glycosylated Ser/Thr in mucins.", "mechanism": "OgpA-mediated mucin degradation regulates mucus thickness and gut barrier integrity.", "protein": "OgpA (O-glycopeptidase from Akkermansia muciniphila)", "relationship_type": "protective", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Type II Diabetes", "glycan_involvement": "O-glycan selectivity modulates mucin degradation and barrier function.", "mechanism": "A. muciniphila activity (via OgpA) improves gut barrier, reducing metabolic disease risk.", "protein": "OgpA (O-glycopeptidase from Akkermansia muciniphila)", "relationship_type": "protective", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycan-dependent cleavage of mucin peptides.", "mechanism": "Mucin degradation by OgpA supports healthy microbiota and barrier, counteracting obesity.", "protein": "OgpA (O-glycopeptidase from Akkermansia muciniphila)", "relationship_type": "protective", "source_pmcid": "PMC11968330" }, { "confidence": "medium", "disease": "Gut Dysbiosis", "glycan_involvement": "O-glycosylation pattern shifts detectable in disease.", "mechanism": "Changes in MUC2 glycosylation profile reflect dysbiotic states.", "protein": "Mucin 2 (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC11968330" }, { "confidence": "high", "disease": "Kidney disease", "glycan_involvement": "N-glycosylation modulates AGP's stability and function as an acute phase reactant", "mechanism": "AGP increases when glomerular filtration is impaired; correlates with urinary albumin-creatinine ratio (UACR)", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "N-glycosylation affects AGP's anti-inflammatory properties", "mechanism": "Elevated AGP reflects ongoing inflammation and is independently associated with renal outcomes", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "N-glycosylation required for AGP's acute phase response", "mechanism": "AGP levels fluctuate in response to acute renal injury and inflammation", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Altered glycosylation may affect AGP's anti-inflammatory function in diabetes", "mechanism": "AGP and UACR jointly indicate early kidney injury in diabetes", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Hypertension-induced kidney injury", "glycan_involvement": "N-glycosylation modulates AGP's immune regulatory role", "mechanism": "AGP elevation reflects inflammatory state and renal damage in hypertension", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "Glycosylation impacts AGP's anti-inflammatory activity", "mechanism": "AGP increases with glomerular inflammation and damage", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. 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Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate AGP's anti-inflammatory effects in SLE", "mechanism": "Elevated AGP indicates systemic inflammation; increased UACR suggests renal involvement", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "high", "disease": "Early renal impairment (esp. type 2 diabetes)", "glycan_involvement": "N-glycosylation critical for ORM1's stability and detection", "mechanism": "Urinary ORM1-to-creatinine ratio is a sensitive marker for early renal impairment", "protein": "Orosomucoid 1 (ORM1)", "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "medium", "disease": "Kidney disease progression", "glycan_involvement": "Glycosylation affects CRP's inflammatory signaling", "mechanism": "Elevated CRP is negatively correlated with eGFR, indicating risk of kidney disease progression", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11973102" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Increased Gal\u03b23GalNAc, decreased core fucose, high mannose, GlcNAc, GalNAc, Gal\u03b24GlcNAc.", "mechanism": "Altered IgG glycosylation profiles distinguish SLE from controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "high", "disease": "Neuropsychiatric SLE (NPSLE)", "glycan_involvement": "Higher galactose and Gal\u03b23GalNAc patterns.", "mechanism": "Elevated IgG galactose and GalNAc glycosylation in NPSLE compared to WMOI.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "Elevated Gal\u03b23GalNAc and galactose.", "mechanism": "LN patients show increased IgG Gal\u03b23GalNAc and galactose glycosylation compared to healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "medium", "disease": "SLE without major organ involvement (WMOI)", "glycan_involvement": "Reduced galactose and GalNAc.", "mechanism": "WMOI patients have lower IgG galactose and GalNAc glycosylation than NPSLE and healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "medium", "disease": "Primary Sj\u00f6gren\u2019s Syndrome (pSS)", "glycan_involvement": "Altered galactose exposure detected by PNA.", "mechanism": "PNA lectin binding to IgG moderately discriminates SLE from pSS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Distinct galactose and Gal\u03b23GalNAc levels.", "mechanism": "IgG glycosylation profiles differ between SLE and RA, especially in galactose and 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"mechanism": "Patients with anti-dsDNA positivity have higher IgG core fucose, sialic acid, GlcNAc, and GalNAc glycosylation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "low", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Altered galactose and GalNAc patterns.", "mechanism": "PAH subgroup shows glycosylation changes similar to other SLE subtypes, but sample size limits confidence.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11973783" }, { "confidence": "low", "disease": "Immune Thrombocytopaenia (ITP)", "glycan_involvement": "Altered 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Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11976851" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Increased sialylation of N-glycans associated with higher triglycerides, BMI, and glucose.", "mechanism": "Fibrinogen glycosylation (especially sialylation) correlates with cardiovascular risk factors (triglycerides, BMI, glucose).", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11976851" }, { "confidence": "medium", "disease": "End-Stage Renal Disease", "glycan_involvement": "Increase in multiantennary N-glycans and altered fucosylation patterns.", "mechanism": "Aberrant N-glycosylation (multiantennary glycans, altered fucosylation) observed in ESRD.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11976851" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Disease-specific changes in N-glycan structures.", "mechanism": "Altered glycosylation patterns may contribute to coagulation abnormalities in cirrhosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11976851" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycation (not classical glycosylation) modifies fibrinogen structure and function.", "mechanism": "Nonenzymatic glycation of fibrinogen leads to fibrin structures resistant to plasmin degradation, increasing cardiovascular complications.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "low", "disease": "Arthritis", "glycan_involvement": "Role of glycosylation not directly specified, but fibrinogen's interactions are glycan-modulated.", "mechanism": "Fibrinogen-deficient mice show reduced inflammation in arthritis models.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "Glycosylation may modulate inflammatory interactions.", "mechanism": "Fibrinogen-deficient mice exhibit reduced inflammation in colitis models.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "low", "disease": "Muscular Dystrophy", "glycan_involvement": "Glycosylation may influence immune interactions.", "mechanism": "Fibrinogen-deficient mice show reduced inflammation in muscular dystrophy models.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "high", "disease": "Thrombotic Events", "glycan_involvement": "Loss of sialic acid from N-glycans enhances clot formation.", "mechanism": "Desialylated fibrinogen produces thicker fibrin fibers and shorter clotting times, increasing thrombotic risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates fibrinogen's inflammatory and coagulation functions.", "mechanism": "Elevated fibrinogen levels and altered glycosylation enhance blood viscosity, endothelial activation, and leukocyte recruitment.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11976851" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy R8 (LGMDR8)", "glycan_involvement": "No direct evidence of glycosylation involvement; disease mechanism is primarily ubiquitination-related.", "mechanism": "Pathogenic variants (especially in NHL repeats, e.g., D487N) impair TRIM32's E3 ubiquitin ligase activity, leading to defective ubiquitination and accumulation of substrate proteins in muscle cells.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "causal", "source_pmcid": "PMC11978422" }, { "confidence": "high", "disease": "Sarcotubular myopathy (STM)", "glycan_involvement": "No direct evidence of glycosylation involvement; mechanism relates to ubiquitination.", "mechanism": "Mutations (e.g., D487N) in TRIM32 cause STM, with overlapping clinical and histological features with LGMDR8, but generally earlier onset and more severe weakness.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "causal", "source_pmcid": "PMC11978422" }, { "confidence": "high", "disease": "Bardet-Biedl Syndrome (BBS)", "glycan_involvement": "No direct evidence; mechanism is domain-specific mutation effect.", "mechanism": "Mutations in the B-box domain of TRIM32 cause BBS, a pleiotropic syndrome without muscle involvement, suggesting domain-specific pathogenic mechanisms.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "causal", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Scapuloperoneal dystrophy", "glycan_involvement": "No direct evidence.", "mechanism": "Certain TRIM32 mutations are associated with scapuloperoneal dystrophy phenotype.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "causal", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Respiratory insufficiency (secondary to myopathy)", "glycan_involvement": "No direct evidence.", "mechanism": "Progressive muscle weakness due to TRIM32 mutation leads to respiratory muscle involvement.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "causal", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Calf hypertrophy (phenotypic feature)", "glycan_involvement": "No direct evidence.", "mechanism": "TRIM32 mutations often present with lower limb hypertrophy.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "biomarker", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Elevated serum creatine kinase (CK)", "glycan_involvement": "No direct evidence.", "mechanism": "Muscle damage due to TRIM32 mutation leads to CK elevation.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "biomarker", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Vacuolar myopathy (histological feature)", "glycan_involvement": "No direct evidence.", "mechanism": "TRIM32 mutations cause vacuolar changes in muscle fibers, seen in STM and LGMDR8.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "biomarker", "source_pmcid": "PMC11978422" }, { "confidence": "medium", "disease": "Exercise intolerance/myalgia", "glycan_involvement": "No direct evidence.", "mechanism": "Early symptom in patients with TRIM32 mutations.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "biomarker", "source_pmcid": "PMC11978422" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "No direct evidence.", "mechanism": "One case reported co-occurrence; no mechanistic link established.", "protein": "TRIM32", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703)", "gene_name": "TRIM32", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13049" }, "relationship_type": "association", "source_pmcid": "PMC11978422" }, { "confidence": "high", "disease": "LGMD R1 (Calpainopathy)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Deficiency of muscle-specific calpain-3 leads to proteolytic enzyme defect and muscle degeneration.", "protein": "Calpain-3", "relationship_type": "causal", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R2 (Dysferlinopathy)", "glycan_involvement": "Dysferlin is a glycoprotein; glycosylation may affect membrane localization and function.", "mechanism": "Dysferlin deficiency impairs sarcolemma repair, causing muscle degeneration.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R3 (Alpha-sarcoglycanopathy)", "glycan_involvement": "Transmembrane glycoprotein; glycosylation required for complex formation.", "mechanism": "Mutations reduce alpha-sarcoglycan, destabilizing sarcoglycan complex and sarcolemma.", "protein": "Alpha-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R4 (Beta-sarcoglycanopathy)", "glycan_involvement": "Glycosylation required for membrane stability.", "mechanism": "Deficiency leads to severe muscular dystrophy and cardiomyopathy; gene therapy restores function.", "protein": "Beta-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R5 (Gamma-sarcoglycanopathy)", "glycan_involvement": "Glycosylation required for sarcoglycan complex integrity.", "mechanism": "Deficiency causes muscle and cardiac pathology; gene therapy under investigation.", "protein": "Gamma-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R6 (Delta-sarcoglycanopathy)", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "Deficiency leads to muscle and cardiac dysfunction.", "protein": "Delta-sarcoglycan", "protein_enriched": { "function": "Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix", "gene_name": "SGCE", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G06110VR", "G31852PQ", "G41247ZX", "G64527OM", "G80920RR" ], "uniprot_id": "O43556" }, "relationship_type": "causal", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "LGMD R9 (FKRP-related)", "glycan_involvement": "FKRP catalyzes ribitol-5-phosphate addition to O-mannosyl glycans on alpha-dystroglycan.", "mechanism": "FKRP deficiency impairs glycosylation of alpha-dystroglycan; ribitol supplementation increases glycosylation.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "Muscular Dystrophy-Dystroglycanopathies", "glycan_involvement": "O-mannosyl glycosylation is essential for function.", "mechanism": "Hypoglycosylation of alpha-dystroglycan impairs extracellular matrix binding, causing muscle pathology.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11978432" }, { "confidence": "medium", "disease": "LGMD R9 (FKRP-related)", "glycan_involvement": "GALGT2 modifies glycan structures on muscle proteins.", "mechanism": "Gene therapy with GALGT2 reduces muscle pathology in FKRP-deficient models.", "protein": "B4GALNT2 (GALGT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11978432" }, { "confidence": "medium", "disease": "Muscle Ischemia", "glycan_involvement": "Indirect; glycoprotein complex integrity affects nNOS localization.", "mechanism": "Mislocalization of nNOS due to sarcoglycan/dystrophin deficiency impairs NO signaling, causing ischemia.", "protein": "Neuronal Nitric Oxide Synthase (nNOS)", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Prob", "gene_name": "NOS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29475" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11978432" }, { "confidence": "high", "disease": "MPI-congenital disorder of glycosylation (MPI-CDG)", "glycan_involvement": "Defective synthesis of N-linked glycans on glycoproteins.", "mechanism": "Loss-of-function mutations in MPI gene disrupt N-glycosylation pathway.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "high", "disease": "MPI-congenital disorder of glycosylation (MPI-CDG)", "glycan_involvement": "Reduced sialylation of N-glycans.", "mechanism": "Abnormal isoelectric focusing pattern due to hypoglycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11980699" }, { "confidence": "medium", "disease": "Coagulation disorder", "glycan_involvement": "Impaired N-glycosylation affects antithrombin stability/function.", "mechanism": "Hypoglycosylation leads to antithrombin deficiency and coagulation abnormalities.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "medium", "disease": "Immunodeficiency (IgM abnormality)", "glycan_involvement": "Defective N-glycosylation of IgM.", "mechanism": "Hypoglycosylation impairs IgM secretion and function.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "low", "disease": "Hyperinsulinemic hypoglycemia", "glycan_involvement": "Defective N-glycosylation of membrane receptors.", "mechanism": "Hypoglycosylation of insulin receptor may alter insulin signaling.", "protein": "Insulin receptor (hypothesized)", "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "low", "disease": "Hyperinsulinemic hypoglycemia", "glycan_involvement": "Defective N-glycosylation of SUR1.", "mechanism": "Hypoglycosylation of SUR1 may affect insulin release.", "protein": "SUR1 (ABCC8)", "protein_enriched": { "function": "Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release. In pancreatic cells, it forms KATP channels with KCNJ11; KCNJ11 forms", "gene_name": "ABCC8", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q09428" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "high", "disease": "Protein-losing enteropathy", "glycan_involvement": "Impaired N-glycosylation in gut epithelium.", "mechanism": "MPI deficiency leads to hypoglycosylation of intestinal glycoproteins.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "high", "disease": "Congenital hepatic fibrosis", "glycan_involvement": "Defective N-glycosylation in hepatic tissue.", "mechanism": "Hypoglycosylation affects liver matrix proteins, causing fibrosis.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "medium", "disease": "Crohn's disease-like enteropathy", "glycan_involvement": "Impaired N-glycosylation in intestinal mucosa.", "mechanism": "Hypoglycosylation of intestinal glycoproteins mimics Crohn's disease.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "causal", "source_pmcid": "PMC11980699" }, { "confidence": "high", "disease": "MPI-congenital disorder of glycosylation (MPI-CDG)", "glycan_involvement": "Exogenous mannose enables N-glycan synthesis.", "mechanism": "Oral mannose supplementation bypasses MPI defect, restoring glycosylation.", "protein": "Mannose phosphate isomerase (MPI)", "protein_enriched": { "function": "Isomerase that catalyzes the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions", "gene_name": "MPI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34949" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11980699" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "O-glycosylation of mucosal proteins and immune molecules may modulate immune responses.", "mechanism": "Enrichment of O-glycan biosynthesis pathways in gut microbiota of vitiligo patients suggests altered glycosylation may affect immune recognition and gut barrier function.", "protein": "O-glycans", "relationship_type": "causal", "source_pmcid": "PMC11988336" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N- and O-glycosylation of IgG affects its immunomodulatory function.", "mechanism": "Altered IgG glycosylation patterns observed in rheumatoid arthritis; modulation of IgG sialylation can attenuate autoimmune disease in models.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11988336" }, { "confidence": "medium", "disease": "Chronic gastritis", "glycan_involvement": "Altered O-glycosylation of mucins affects barrier and immune function.", "mechanism": "Helicobacter suis infection changes mucin glycosylation, impairing mucus-based defenses and promoting gastritis.", "protein": "Mucins", "relationship_type": "causal", "source_pmcid": "PMC11988336" }, { "confidence": "medium", "disease": "Peptic ulcer disease", "glycan_involvement": "O-glycosylation changes in mucins reduce protective function.", "mechanism": "Helicobacter species alter mucin glycosylation, weakening mucosal protection and contributing to ulcer formation.", "protein": "Mucins", "relationship_type": "causal", "source_pmcid": "PMC11988336" }, { "confidence": "low", "disease": "Gastric MALT lymphoma", "glycan_involvement": "Altered O-glycosylation impacts immune cell interactions.", "mechanism": "Helicobacter suis-induced mucin glycosylation changes may facilitate lymphoid tissue transformation.", "protein": "Mucins", "relationship_type": "causal", "source_pmcid": "PMC11988336" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "O-glycosylation of mucosal proteins regulates microbial interactions and immune responses.", "mechanism": "Gut bacteria utilize O-glycans for energy; altered O-glycan biosynthesis may affect gut barrier and inflammation.", "protein": "O-glycans", "relationship_type": "causal/protective", "source_pmcid": "PMC11988336" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Indirect\u2014modulates host glycosylation via SCFA production.", "mechanism": "Reduced abundance in vitiligo; produces butyrate, which induces Treg cells and anti-inflammatory effects.", "protein": "Faecalibacterium prausnitzii (butyrate producer)", "relationship_type": "protective", "source_pmcid": "PMC11988336" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Indirect\u2014SCFA production may influence glycosylation.", "mechanism": "Reduced in vitiligo; produces butyrate and SCFAs, supporting epithelial metabolism and immune regulation.", "protein": "Faecalibacterium duncaniae (butyrate producer)", "relationship_type": "protective", "source_pmcid": "PMC11988336" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Utilizes host O-glycans for energy; may modulate glycosylation patterns.", "mechanism": "Increased abundance in vitiligo patients; role unclear, may reflect reduced overall diversity.", "protein": "Bifidobacterium bifidum", "relationship_type": "biomarker", "source_pmcid": "PMC11988336" }, { "confidence": "high", "disease": "Autoimmune diseases (general)", "glycan_involvement": "O-glycosylation changes affect immune cell interactions and antigenicity.", "mechanism": "Altered O-glycosylation patterns implicated in immune recognition and autoimmune pathogenesis.", "protein": "O-glycans", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11988336" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease (MEB)", "glycan_involvement": "Defective O-mannosylation of \u03b1-dystroglycan", "mechanism": "Biallelic loss-of-function variants in POMGNT1 impair O-mannosyl glycan synthesis on \u03b1-dystroglycan, disrupting basal membrane assembly in muscle, brain, and retina.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Retinitis pigmentosa (RP)", "glycan_involvement": "Defective O-mannosylation of \u03b1-dystroglycan in retina", "mechanism": "Biallelic POMGNT1 mutations cause isolated rod-cone dystrophy by disrupting O-mannosylation in photoreceptors.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Non-syndromic inherited retinal dystrophy", "glycan_involvement": "Impaired O-mannosylation of \u03b1-dystroglycan in photoreceptors", "mechanism": "Compound heterozygous POMGNT1 variants lead to variable retinal dystrophy phenotypes without systemic involvement.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Congenital muscular dystrophy-dystroglycanopathy (MDDGA)", "glycan_involvement": "Defective O-mannosylation of \u03b1-dystroglycan", "mechanism": "Loss-of-function POMGNT1 variants disrupt O-mannosyl glycan synthesis, leading to muscular dystrophy with brain and eye anomalies.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Muscle\u2013eye\u2013brain disease (MEB)", "glycan_involvement": "O-mannosylation required for \u03b1-DG function", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan impairs its function in linking cytoskeleton to extracellular matrix, causing MEB.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Congenital muscular dystrophy-dystroglycanopathy (MDDGA)", "glycan_involvement": "O-mannosylation of \u03b1-DG", "mechanism": "Defective O-mannosylation of \u03b1-DG leads to loss of extracellular matrix binding and muscular dystrophy.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "medium", "disease": "Retinitis pigmentosa (RP)", "glycan_involvement": "O-mannosylation at photoreceptor cilium basal body", "mechanism": "Impaired O-mannosylation of \u03b1-DG in photoreceptors disrupts protein transport and retinal integrity.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "medium", "disease": "Muscle\u2013eye\u2013brain disease (MEB)", "glycan_involvement": "Restoration of O-mannosylation", "mechanism": "Restoring POMGNT1 function or O-mannosylation may ameliorate disease features.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Retinitis pigmentosa (RP)", "glycan_involvement": "Genetic marker for O-mannosylation defects", "mechanism": "POMGNT1 mutations can be used as a genetic biomarker for isolated RP.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11989775" }, { "confidence": "medium", "disease": "Non-syndromic inherited retinal dystrophy", "glycan_involvement": "O-mannosylation in photoreceptors", "mechanism": "Partial loss of O-mannosylation on \u03b1-DG in retina leads to isolated retinal dystrophy.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11989775" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Low serum ceruloplasmin is indicative of impaired copper metabolism in WD.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "ATP7B is glycosylated; glycosylation may affect its trafficking and function.", "mechanism": "Mutations in ATP7B disrupt copper excretion, leading to copper accumulation.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC11998279" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Potential O-glycosylation may affect dystrophin stability, but not discussed in article.", "mechanism": "Loss-of-function mutations in dystrophin gene cause muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11998279" }, { "confidence": "medium", "disease": "Muscle lesions", "glycan_involvement": "Glycosylation affects ceruloplasmin's function in copper transport.", "mechanism": "Low ceruloplasmin may contribute to copper-induced muscle damage.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "high", "disease": "Inflammatory response", "glycan_involvement": "IL-6 is glycosylated; glycosylation modulates cytokine activity.", "mechanism": "Elevated IL-6 reflects systemic inflammation in WD and DMD.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "high", "disease": "Inflammatory response", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 indicates inflammation in WD and DMD.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "medium", "disease": "Liver lesions", "glycan_involvement": "Glycosylation may regulate ATP7B localization and function.", "mechanism": "ATP7B mutation leads to copper accumulation, causing liver damage.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC11998279" }, { "confidence": "medium", "disease": "Muscle lesions", "glycan_involvement": "Glycosylation may affect ATP7B stability in muscle cells.", "mechanism": "Copper accumulation due to ATP7B defect can trigger muscle damage.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC11998279" }, { "confidence": "medium", "disease": "Liver lesions", "glycan_involvement": "Glycosylation is essential for ceruloplasmin secretion and function.", "mechanism": "Low ceruloplasmin correlates with copper-induced liver injury.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "medium", "disease": "Wilson's disease", "glycan_involvement": "Glycosylation modulates IL-6 stability and activity.", "mechanism": "Elevated IL-6 is associated with copper-induced inflammation in WD.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC11998279" }, { "confidence": "high", "disease": "FCSK-CDG", "glycan_involvement": "Global reduction in protein fucosylation (N- and O-linked).", "mechanism": "Loss-of-function mutations in FCSK disrupt GDP-fucose salvage pathway, leading to reduced fucosylation of glycoproteins.", "protein": "FCSK (Fucokinase)", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Developmental delay", "glycan_involvement": "O-fucosylation of glycoproteins required for normal development.", "mechanism": "Reduced expression of POFUT2 impairs O-fucosylation, affecting skeletal and brain development.", "protein": "POFUT2", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "N-glycan core fucosylation.", "mechanism": "FUT8 mutations impair core fucosylation of N-glycans, causing CDG with neurological and developmental symptoms.", "protein": "FUT8", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Dowling-Degos disease", "glycan_involvement": "O-fucosylation of epidermal glycoproteins.", "mechanism": "POFUT1 mutations disrupt O-fucosylation, leading to pigmentary abnormalities.", "protein": "POFUT1", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "GDP-fucose transport for glycoprotein fucosylation.", "mechanism": "Defective GDP-fucose transport into Golgi impairs fucosylation, causing immune and developmental symptoms.", "protein": "SLC35C1", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "GDP-fucose biosynthesis for glycoprotein fucosylation.", "mechanism": "GFUS mutations reduce GDP-fucose synthesis, leading to global fucosylation defects.", "protein": "GFUS", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Brain atrophy", "glycan_involvement": "Fucosylation of neuronal glycoproteins.", "mechanism": "Reduced fucosylation impairs neuronal development and survival, leading to brain atrophy.", "protein": "Total fucosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "medium", "disease": "Neurodevelopmental disorders", "glycan_involvement": "Sialylation of glycoproteins.", "mechanism": "Downregulation of sialyltransferase disrupts glycosylation homeostasis, affecting neurodevelopment.", "protein": "ST8SIA7.1", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Indirect; glycosylation defects may affect FUS expression/function.", "mechanism": "Downregulation of FUS in fcsk \u2212/\u2212 zebrafish links fucosylation defects to ALS-like neurodegeneration.", "protein": "FUS", "protein_enriched": { "function": "DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to ssRNA ", "gene_name": "FUS", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI", "G47950XN" ], "uniprot_id": "P35637" }, "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "medium", "disease": "Seizure susceptibility", "glycan_involvement": "Fucosylation of neuronal surface glycoproteins.", "mechanism": "Reduced fucosylation alters neuronal excitability, increasing seizure risk.", "protein": "Total fucosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC12000135" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Defective O-glycosylation (matriglycan) reduces ECM binding.", "mechanism": "Mutations or hypoglycosylation of \u03b1-DG disrupt its interaction with laminin, weakening muscle fiber stability.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Hypoglycosylation of \u03b1-DG matriglycan domain.", "mechanism": "Primary DAG1 mutations or secondary glycosyltransferase defects impair \u03b1-DG glycosylation, leading to disease.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy (LGMD2P)", "glycan_involvement": "Reduced O-glycosylation of matriglycan domain.", "mechanism": "T190M mutation alters \u03b1-DG N-terminal domain dynamics, impairs interaction with LARGE1, causing hypoglycosylation.", "protein": "\u03b1-dystroglycan (\u03b1-DG) T190M mutant", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Likely affects post-translational glycosylation and processing.", "mechanism": "I591D mutation perturbs C-terminal domain, impairs maturation and trafficking, leading to ER retention and loss of function.", "protein": "\u03b1-dystroglycan (\u03b1-DG) I591D mutant", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Muscle-Eye-Brain disease", "glycan_involvement": "Impaired maturation may affect glycosylation status.", "mechanism": "C667F mutation disrupts \u03b2-DG folding, causes ER retention and defective precursor processing.", "protein": "\u03b2-dystroglycan (\u03b2-DG) C667F mutant", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Multicystic leukodystrophy", "glycan_involvement": "Defective processing may alter glycosylation.", "mechanism": "C667F mutation leads to ER retention, oligomerization, and loss of DG at plasma membrane, causing CNS anomalies.", "protein": "\u03b2-dystroglycan (\u03b2-DG) C667F mutant", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Blood-brain barrier destabilization", "glycan_involvement": "Impaired trafficking may affect glycan presentation.", "mechanism": "C667F mutation in mouse model causes myopathy and blood-brain barrier defects due to DG absence at membrane.", "protein": "\u03b2-dystroglycan (\u03b2-DG) C667F mutant", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "low", "disease": "Arrhythmogenic cardiomyopathy", "glycan_involvement": "Potentially affects Ig-like domain, may alter glycosylation indirectly.", "mechanism": "L84F variant may contribute to cardiac disease when combined with PKP2 mutation; pathogenicity not confirmed.", "protein": "\u03b1-dystroglycan (\u03b1-DG) L84F mutant", "relationship_type": "variant of uncertain significance", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Walker-Warburg syndrome", "glycan_involvement": "Loss of matriglycan O-glycosylation.", "mechanism": "Defects in glycosyltransferases cause hypoglycosylated \u03b1-DG, reducing ECM binding and causing severe CMD.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Muscle-Eye-Brain disease", "glycan_involvement": "Defective O-glycosylation of matriglycan domain.", "mechanism": "Hypoglycosylation of \u03b1-DG due to glycosyltransferase mutations impairs ECM interactions.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12003124" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Altered O-glycan structures, including sialylation and O-acetylation, are associated with tumor progression.", "mechanism": "Aberrant O-glycosylation patterns in mucins are frequently observed in cancer and may serve as diagnostic/prognostic biomarkers.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "Aberrant O-glycan profiles may affect protein stability and cell interactions in neural tissues.", "mechanism": "Changes in mucin O-glycosylation are linked to neurodegenerative disease pathology.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "O-glycan changes influence immune cell interactions and antigenicity.", "mechanism": "Altered O-glycosylation in mucins is observed in autoimmune conditions and may serve as a biomarker.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-acetylation patterns of sialic acids can serve as disease markers.", "mechanism": "Distinctive O-acetylated Neu5Ac-containing O-glycans in serum may indicate disease states including cancer.", "protein": "Serum glycoproteins (horse)", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "KDN-modified O-glycans are associated with altered cellular interactions in disease.", "mechanism": "Presence of KDN-containing O-glycans in intestinal tissue may be linked to disease states.", "protein": "Intestinal glycoproteins (fish)", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Targeting aberrant O-glycan structures may modulate tumor cell behavior.", "mechanism": "O-glycosylation sites on mucins are potential targets for cancer therapy.", "protein": "Mucin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12004196" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "Altered O-acetylation affects immune recognition.", "mechanism": "O-acetylated sialic acid patterns in serum glycoproteins may reflect autoimmune activity.", "protein": "Serum glycoproteins (horse)", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Changes in O-glycan composition affect cell-cell and cell-matrix interactions.", "mechanism": "Aberrant O-glycosylation contributes to cancer cell adhesion and metastasis.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12004196" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "KDN-modified glycans influence immune cell interactions.", "mechanism": "KDN-containing O-glycans may serve as markers for intestinal immune dysregulation.", "protein": "Intestinal glycoproteins (fish)", "relationship_type": "biomarker", "source_pmcid": "PMC12004196" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Altered O-glycan structures disrupt neural tissue integrity.", "mechanism": "O-glycosylation impacts mucin stability and neural cell interactions, contributing to neurodegeneration.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12004196" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Reported to be O-glycosylated; may affect antigenicity.", "mechanism": "Induces strong IgG antibody response; used in serological assays.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Mimics C5a activity; not glycosylated itself but modulates glycoprotein-mediated immunity.", "mechanism": "Acts as an adjuvant to enhance IgG response to inactivated SARS-CoV-2 immunization.", "protein": "EP67", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "Murine Hepatitis Virus (MHV) infection", "glycan_involvement": "Acts via C5aR1 pathway, which involves glycoprotein receptor signaling.", "mechanism": "Intranasal EP67 administration post-infection leads to rapid disease resolution.", "protein": "EP67", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12006086" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "C5a is a glycoprotein; glycosylation affects stability and receptor interaction.", "mechanism": "C5a is a potent inflammatory mediator; excessive activation linked to immunopathology.", "protein": "Complement component C5a", "protein_enriched": { "function": "Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling ", "gene_name": "C5", "glycan_count": 29, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G12580WI", "G06356OH", "G48414YA", "G04854VP", "G06247RL", "G08918WF", "G10486CT", "G25418HZ", "G26330YA", "G27058EU", "G27947YN", "G38663NM", "G40574BA", "G40926MX", "G45395BF", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G77669RF", "G84452RH", "G90659AW", "G92551JA", "G94470IW", "G95865ZB", "G42227JK", "G49108TO" ], "uniprot_id": "P01031" }, "relationship_type": "causal", "source_pmcid": "PMC12006086" }, { "confidence": "medium", "disease": "Murine Hepatitis Virus (MHV) infection", "glycan_involvement": "Glycosylation modulates C5a activity and immune cell recruitment.", "mechanism": "C5a-mediated inflammation contributes to granulocyte recruitment and lung pathology.", "protein": "Complement component C5a", "protein_enriched": { "function": "Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling ", "gene_name": "C5", "glycan_count": 29, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G12580WI", "G06356OH", "G48414YA", "G04854VP", "G06247RL", "G08918WF", "G10486CT", "G25418HZ", "G26330YA", "G27058EU", "G27947YN", "G38663NM", "G40574BA", "G40926MX", "G45395BF", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G77669RF", "G84452RH", "G90659AW", "G92551JA", "G94470IW", "G95865ZB", "G42227JK", "G49108TO" ], "uniprot_id": "P01031" }, "relationship_type": "causal", "source_pmcid": "PMC12006086" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) infection", "glycan_involvement": "Acts via C5aR1, a glycoprotein receptor.", "mechanism": "EP67 acts as an adjuvant, enhancing immune protection in murine CMV models.", "protein": "EP67", "relationship_type": "protective", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "Murine Hepatitis Virus (MHV) infection", "glycan_involvement": "N-glycosylation critical for folding, immune evasion, and infectivity.", "mechanism": "Mediates viral entry and pathogenesis in mice.", "protein": "MHV Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "Acute pneumonia (MHV-induced)", "glycan_involvement": "Modulates immune response via glycoprotein receptor C5aR1.", "mechanism": "Reduces disease severity and lung pathology when administered post-infection.", "protein": "EP67", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N-glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Target of neutralizing antibodies and vaccines; immune response enhanced by EP67 adjuvant.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12006086" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation critical for membrane stability and signaling.", "mechanism": "Loss of dystrophin disrupts glycoprotein complex linking cytoskeleton to extracellular matrix, leading to muscle degeneration.", "protein": "Dystrophin-associated glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation required for ECM binding; MMP-9-mediated cleavage disrupts function.", "mechanism": "Dystroglycan bridges dystrophin and ECM; its degradation impairs neural signaling and muscle integrity.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects lipid transport and anti-inflammatory activity.", "mechanism": "ApoE upregulates miR-146a, suppressing inflammation; downregulation leads to lipid accumulation and increased inflammation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective", "source_pmcid": "PMC12019623" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Targets glycosylated dystroglycan for degradation.", "mechanism": "MMP-9 cleaves dystroglycan, impairing neural signaling and muscle function.", "protein": "Matrix metalloprotease-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Upregulated in miR-146a-5p deficiency, promoting fibrotic gene expression.", "protein": "Transforming growth factor beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects membrane localization and function.", "mechanism": "CAV1 inhibits TGF-\u03b21-mediated fibrosis; downregulated by miR-199a-5p in DMD exosomes.", "protein": "Caveolin 1 (CAV1)", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (PubMed:11751885). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the ", "gene_name": "CAV1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q03135" }, "relationship_type": "protective", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Muscle atrophy", "glycan_involvement": "Glycosylation may affect PTEN stability and activity.", "mechanism": "Upregulated PTEN (due to miR-132-3p downregulation) promotes apoptosis and muscle wasting.", "protein": "Phosphatase and tensin homolog (PTEN)", "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates lipid binding and clearance.", "mechanism": "ApoE deficiency leads to increased plasma lipids and plaque formation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "O-mannosylation essential for brain ECM interactions.", "mechanism": "Reduced dystroglycan impairs neural signaling, contributing to cognitive deficits in DMD and ASD.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects collagen secretion and ECM assembly.", "mechanism": "Upregulated in response to decreased CAV1, contributing to tissue fibrosis.", "protein": "Collagen, type I, alpha 1", "relationship_type": "causal", "source_pmcid": "PMC12019623" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Glycosylation of CFTR is required for proper folding and trafficking; mutations may affect glycosylation and membrane localization.", "mechanism": "Mutations (e.g., p.Phe508del, p.Phe312del) in CFTR disrupt chloride transport, leading to CF symptoms.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "CFTR-associated diseases", "glycan_involvement": "Glycosylation status may influence residual function and phenotype.", "mechanism": "Certain CFTR mutations (e.g., p.Phe312del in compound heterozygosity) result in variable or absent clinical manifestations despite elevated sweat chloride.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Altered glycosylation may affect CFTR function and biomarker reliability.", "mechanism": "Sweat chloride elevation is a diagnostic biomarker for CF, reflecting CFTR dysfunction.", "protein": "CFTR", "relationship_type": "biomarker", "source_pmcid": "PMC12020654" }, { "confidence": "medium", "disease": "Cystic Fibrosis", "glycan_involvement": "Preserved glycosylation enables proper folding and trafficking.", "mechanism": "p.Phe312del mutation allows synthesis of mature, functional CFTR protein, reducing clinical manifestations despite genetic diagnosis.", "protein": "CFTR", "relationship_type": "protective", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Becker's Muscular Dystrophy", "glycan_involvement": "Glycosylation may affect dystrophin stability and muscle membrane interactions.", "mechanism": "In-frame deletions in dystrophin gene cause BMD, leading to muscle breakdown and elevated CK/ALT.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Glycosylation affects IRT secretion and stability.", "mechanism": "Elevated IRT in newborn screening is used as a biomarker for CF.", "protein": "IRT", "relationship_type": "biomarker", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Misfolded CFTR is degraded before glycosylation is completed, preventing membrane localization.", "mechanism": "p.Phe508del mutation causes misfolding and defective trafficking of CFTR, resulting in loss of function.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Glycosylation of p.Phe312del variant supports partial function.", "mechanism": "Compound heterozygosity for p.Phe312del/p.Phe508del can result in elevated sweat chloride but variable or absent clinical CF.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12020654" }, { "confidence": "medium", "disease": "Cystic Fibrosis", "glycan_involvement": "CFTR glycosylation status may indirectly affect pancreatic secretion.", "mechanism": "Stool elastase is used to assess exocrine pancreatic function in CF.", "protein": "CFTR", "relationship_type": "biomarker", "source_pmcid": "PMC12020654" }, { "confidence": "medium", "disease": "Becker's Muscular Dystrophy", "glycan_involvement": "Glycosylation may influence dystrophin's interaction with muscle cell membranes.", "mechanism": "Elevated CK and transaminases are biomarkers for muscle breakdown in BMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12020654" }, { "confidence": "high", "disease": "Congenital stationary night blindness", "glycan_involvement": "Nyctalopin is a glycoprotein; glycosylation may affect stability and localization.", "mechanism": "Nyctalopin mutations cause loss of TRPM1 localization at ON bipolar cell dendrites, abolishing ON pathway transmission.", "protein": "Nyctalopin", "protein_enriched": { "function": "Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal. Imposes pluripotency on ES cells and prevents their differentiation towards extraembry", "gene_name": "NANOG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H9S0" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "high", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "Pikachurin is heavily glycosylated; glycosylation is required for dystroglycan binding and synaptic localization.", "mechanism": "Loss of Pikachurin impairs invaginating synapses between photoreceptors and ON bipolar cells, reducing ERG responses.", "protein": "Pikachurin", "protein_enriched": { "function": "Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905, PubMed:37267906). The FERRY complex directly interacts with mRNAs and RAB5A, and functions ", "gene_name": "PPP1R21", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G06356OH", "G48414YA", "G59626AS" ], "uniprot_id": "Q6ZMI0" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "high", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "Dystroglycan glycosylation is essential for Pikachurin interaction and synaptic function.", "mechanism": "Dystroglycan KO disrupts ON bipolar cell invaginations and ERG responses.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "high", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "ELFN1 is a glycoprotein; glycosylation may regulate synaptic targeting.", "mechanism": "ELFN1 KO reduces rod to ON bipolar cell contacts and mGluR6 expression, abolishing dim-light ERG b-wave.", "protein": "ELFN1", "protein_enriched": { "function": "", "gene_name": "UMODL1-AS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N2C9" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "medium", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "ELFN2 is a glycoprotein; glycosylation may affect synaptic localization.", "mechanism": "ELFN2 KO impairs cone to ON bipolar cell synaptic function when combined with ELFN1 loss.", "protein": "ELFN2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N2C8" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "high", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "LRIT3 is a glycoprotein; glycosylation may affect stability and synaptic targeting.", "mechanism": "LRIT3 KO abolishes ON responses and slows OFF responses in retinal ganglion cells.", "protein": "LRIT3", "protein_enriched": { "function": "Auxiliary subunit of the NALCN sodium channel complex, a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (By similarity). Activated by neur", "gene_name": "UNC80", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N2C7" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "medium", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "SynCAM1 is N-glycosylated; glycosylation may regulate adhesion and synaptic assembly.", "mechanism": "SynCAM1 KO leads to shorter rod ribbons and fewer triadic synapses, impairing rod transmission.", "protein": "SynCAM1", "protein_enriched": { "function": "Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquit", "gene_name": "UBE4B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95155" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "medium", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "NGL2 is a glycoprotein; glycosylation may affect transsynaptic interactions.", "mechanism": "NGL2 KO causes HC axonal overgrowth and fewer rod synapses, disrupting ribbon assembly.", "protein": "NGL2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N2C6" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "medium", "disease": "Visual acuity impairment", "glycan_involvement": "AMIGO1 is a glycoprotein; glycosylation may regulate cell surface expression.", "mechanism": "AMIGO1 KO shrinks HC axonal arbors and mislaminates HCs, but does not affect synaptic density.", "protein": "AMIGO1", "protein_enriched": { "function": "", "gene_name": "KIR3DL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N6C9" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "medium", "disease": "Retinal synaptic transmission defects", "glycan_involvement": "LRRTM4 is a glycoprotein; glycosylation may affect receptor clustering.", "mechanism": "LRRTM4 KO reduces GABA receptor clustering at RBC terminals, decreasing presynaptic inhibition.", "protein": "LRRTM4", "protein_enriched": { "function": "May contribute to specialized endoplasmic reticulum functions in neurons", "gene_name": "SEZ6L2", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G06356OH", "G15169WU", "G22310AV", "G31665QC", "G35107SO", "G46503DX", "G48414YA", "G56784JY", "G74728JK", "G75983OB", "G89205CJ", "G51653BI", "G47518TP", "G62765YT", "G69521XL", "G80920RR", "G53434XO", "G29068FM", "G43417UB", "G16125XL", "G83633GK" ], "uniprot_id": "Q6UXD5" }, "relationship_type": "causal", "source_pmcid": "PMC12022667" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "O-glycosylation (matriglycan) is essential for laminin binding; defects cause disease.", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan impairs laminin binding, disrupting basement membrane stability and causing muscular dystrophy, brain malformation, and ocular defects.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Loss of O-glycosylation (matriglycan) reduces laminin binding, facilitating cancer cell invasion.", "mechanism": "Reduced matriglycan and \u03b1-dystroglycan expression/glycosylation correlates with poor prognosis and promotes tumor progression/metastasis.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Viral Infection (Lassa virus)", "glycan_involvement": "Matriglycan (O-glycosylation) is the viral binding site.", "mechanism": "Lassa virus uses matriglycan on \u03b1-dystroglycan as a receptor for cell entry.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Not specified; protein-protein interaction predominates.", "mechanism": "Overexpression promotes tumor cell adhesion, migration, invasion, and metastasis via laminin binding.", "protein": "67-kDa Laminin Receptor", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12026610" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified.", "mechanism": "67 kDa LR mediates amyloid beta uptake and APP processing, contributing to neurodegeneration.", "protein": "67-kDa Laminin Receptor", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Wound Healing Defects", "glycan_involvement": "GAG chains on syndecan-1 mediate laminin binding.", "mechanism": "Syndecan-1/laminin 332 interaction is crucial for keratinocyte migration and ECM remodeling during wound repair.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "GAG modifications regulate laminin binding and signaling.", "mechanism": "Syndecan-laminin interaction promotes tumor cell adhesion, invasion, and angiogenesis; targeted therapies (e.g., BT062) show efficacy.", "protein": "Syndecan-1/-2/-4", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Sickle Cell Disease", "glycan_involvement": "Sialic acid loss during erythrocyte aging enhances laminin binding.", "mechanism": "Phosphorylation or dissociation from spectrin increases Lu/BCAM-mediated red blood cell adhesion to laminin, contributing to vaso-occlusion.", "protein": "Lu/BCAM", "relationship_type": "causal", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Metastatic Colorectal Cancer", "glycan_involvement": "Sialic acid-dependent interaction with laminin \u03b15.", "mechanism": "Lu/BCAM overexpression promotes adhesion to vascular endothelium via laminin \u03b15, facilitating hepatic metastasis; inhibition reduces metastasis.", "protein": "Lu/BCAM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Not specified.", "mechanism": "MCAM+ CD4+ T cells bind laminin 411 to infiltrate CNS, driving neuroinflammation; antibody blockade reduces disease severity.", "protein": "MCAM", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12026610" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "None; dystrophin itself is not glycosylated.", "mechanism": "Loss-of-function mutations in DMD gene cause absence or deficiency of dystrophin, leading to muscle fiber instability and degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12027135" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "None; dystrophin itself is not glycosylated.", "mechanism": "Partially functional dystrophin due to in-frame mutations results in milder muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12027135" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b2-dystroglycan is a glycoprotein; glycosylation is required for proper complex formation.", "mechanism": "\u03b2-dystroglycan is part of the dystrophin-glycoprotein complex; its interaction with dystrophin is essential for membrane stability.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12027135" }, { "confidence": "high", "disease": "Dystroglycanopathies", "glycan_involvement": "O-glycosylation is critical for \u03b1-dystroglycan function.", "mechanism": "Defective glycosylation of \u03b1-dystroglycan impairs its binding to extracellular matrix, causing muscle pathology.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12027135" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Therapeutic modulation of O-glycosylation.", "mechanism": "Enhancing \u03b1-dystroglycan glycosylation can restore ECM binding and partially compensate for dystrophin loss.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12027135" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "None directly; utrophin is not a glycoprotein.", "mechanism": "Upregulation of utrophin compensates for dystrophin deficiency by stabilizing the DGC.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12027135" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Indirect; interacts with glycoprotein complex.", "mechanism": "Syntrophin binds to dystrophin and \u03b2-dystroglycan, contributing to DGC stability.", "protein": "Syntrophin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12027135" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "None.", "mechanism": "nNOS localization to sarcolemma is dystrophin-dependent; loss leads to impaired signaling.", "protein": "Neuronal nitric oxide synthase (nNOS)", "relationship_type": "biomarker", "source_pmcid": "PMC12027135" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "None.", "mechanism": "Used as a normalization control in dystrophin quantification assays.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12027135" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Loss of \u03b2-dystroglycan disrupts DGC, leading to myocardial dysfunction.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12027135" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Sialylation of Fc N-glycans modulates IgG's inflammatory activity.", "mechanism": "Low sialylation of IgG correlates with increased inflammation and RA progression; high sialylation is protective.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12027927" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Catalyzes addition of sialic acid to IgG N-glycans.", "mechanism": "Estrogen upregulates ST6GAL1, increasing IgG sialylation and reducing RA inflammation.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "protective", "source_pmcid": "PMC12027927" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "CR1 is a glycoprotein; glycosylation may affect its cell surface expression and function.", "mechanism": "Estrogen increases CR1 expression on B cells, reducing inflammation in RA mouse models.", "protein": "CR1", "relationship_type": "protective", "source_pmcid": "PMC12027927" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "OPG glycosylation affects its stability and receptor binding.", "mechanism": "Estrogen stimulates OPG production, inhibiting osteoclastogenesis and bone destruction in RA.", "protein": "OPG", "relationship_type": "protective", "source_pmcid": "PMC12027927" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation modulates TNF secretion and receptor interaction.", "mechanism": "TNF promotes inflammation and osteoclastogenesis in RA.", "protein": "TNF", "relationship_type": "causal", "source_pmcid": "PMC12027927" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation affects IL-6 stability and signaling.", "mechanism": "IL-6 drives inflammation and bone resorption in RA.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12027927" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation influences M-CSF receptor binding.", "mechanism": "M-CSF promotes osteoclast differentiation, contributing to bone loss in RA.", "protein": "M-CSF", "relationship_type": "causal", "source_pmcid": "PMC12027927" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation modulates RANKL activity.", "mechanism": "RANKL stimulates osteoclastogenesis and bone erosion in RA.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal", "source_pmcid": "PMC12027927" }, { "confidence": "low", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "BMPs are glycoproteins; glycosylation affects their signaling.", "mechanism": "Estrogen increases BMP signaling, promoting osteoblast differentiation and bone formation.", "protein": "BMPs", "relationship_type": "protective", "source_pmcid": "PMC12027927" }, { "confidence": "low", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "ER glycosylation may affect receptor function and hormone binding.", "mechanism": "Estrogen binding to ER modulates immune response, shifting Th1/Th2 balance and enhancing Treg function.", "protein": "Estrogen receptor (ER)", "relationship_type": "protective", "source_pmcid": "PMC12027927" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AGP contains multiple N-glycosylation sites; glycosylation may affect its function in inflammation and lipid metabolism.", "mechanism": "AGP levels are significantly and positively correlated with NAFLD prevalence and hepatic steatosis severity.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "high", "disease": "Liver fibrosis (LF)", "glycan_involvement": "AGP glycosylation (especially fucosylation) may reflect fibrosis severity.", "mechanism": "AGP levels are positively associated with liver fibrosis; higher AGP predicts increased fibrosis risk.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Changes in AGP glycosylation structure (e.g., fucosylation) linked to cirrhosis.", "mechanism": "AGP levels increase in cirrhosis; altered glycosylation patterns observed.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered AGP glycosylation may contribute to diagnostic utility.", "mechanism": "Combined AGP and AFP assays improve early HCC diagnosis in cirrhotic patients.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation may modulate AGP's regulatory effects on lipid metabolism.", "mechanism": "AGP may suppress SREBP1c-mediated lipogenesis, potentially inhibiting NAFLD progression.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Liver fibrosis (LF)", "glycan_involvement": "Glycosylation changes may influence AGP's pro-fibrotic activity.", "mechanism": "Experimental AGP administration accelerates fibrosis in chronic liver injury models.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect AGP's interaction with metabolic pathways.", "mechanism": "AGP levels are associated with insulin resistance and T2DM risk in NAFLD patients.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation may regulate AGP's anti-steatotic function.", "mechanism": "At high AGP (>1.2 g/L), AGP may inhibit further hepatic steatosis via AMPK/SREBP1c pathway.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "protective", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Liver fibrosis (LF)", "glycan_involvement": "Fucosylation of AGP N-glycans correlates with fibrosis stage.", "mechanism": "AGP fucosylation level may predict fibrosis severity.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Loss of sialylation on AGP N-glycans increases diagnostic sensitivity.", "mechanism": "Serum asialo-AGP is an independent risk factor for cirrhosis prediction in NAFLD progression.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12029307" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Antibody glycosylation (e.g., afucosylation) enhances ADCC.", "mechanism": "CD20-targeting mAbs (ocrelizumab, ofatumumab) deplete B-cells via ADCC/CDC, reducing disease activity.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "Afucosylation of IgG1 increases Fc\u03b3RIIIa binding and ADCC.", "mechanism": "Anti-CD19 mAb (inebilizumab) depletes B-cells, reducing autoantibody production and NMOSD attacks.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation of BAFF and mAb may affect binding/efficacy.", "mechanism": "Belimumab neutralizes soluble BAFF, inhibiting B-cell survival and autoantibody production.", "protein": "BAFF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "medium", "disease": "Sj\u00f6gren\u2019s Syndrome", "glycan_involvement": "Glycosylation may affect receptor-ligand interactions.", "mechanism": "Ianalumab targets BAFF-R, lysing B-cells and blocking BAFF-mediated survival signaling.", "protein": "BAFF-R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Fusion protein format may alter glycosylation, impacting stability and immunogenicity.", "mechanism": "Dazodalibep antagonizes CD40L, blocking T-cell/B-cell co-stimulation and reducing inflammation.", "protein": "CD40L", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Bispecific antibody glycosylation affects stability and function.", "mechanism": "PRV-3279 bispecific antibody crosslinks CD32B and CD79B, downregulating B-cell receptor signaling.", "protein": "CD32B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fusion protein glycosylation impacts pharmacokinetics and aggregation.", "mechanism": "Fc fusion proteins (telitacicept, atacicept) neutralize APRIL and BAFF, reducing B-cell survival.", "protein": "APRIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "medium", "disease": "Pemphigus", "glycan_involvement": "Antibody glycosylation modulates effector function.", "mechanism": "CD20-targeting mAbs deplete pathogenic B-cells, reducing autoantibody-mediated skin blistering.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "high", "disease": "IgG4-Related Disease (IgG4-RD)", "glycan_involvement": "Afucosylation enhances B-cell depletion.", "mechanism": "Inebilizumab depletes B-cells, reducing IgG4 autoantibody production and disease flares.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "high", "disease": "Myasthenia Gravis", "glycan_involvement": "Afucosylated IgG1 increases ADCC.", "mechanism": "Inebilizumab depletes B-cells, reducing pathogenic autoantibodies and improving symptoms.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12030081" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates host cell entry via receptor binding; determines species specificity and cross-species transmission.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "high", "disease": "Porcine epidemic diarrhea", "glycan_involvement": "Glycosylation affects host receptor interaction and tropism.", "mechanism": "Spike protein of PEDV enables entry into swine cells, causing diarrhea.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "high", "disease": "Human coronavirus infection (HCoV-229E, NL63)", "glycan_involvement": "Glycosylation influences receptor binding and immune escape.", "mechanism": "Spike protein binds human APN or ACE2, mediating infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "high", "disease": "Porcine epidemic diarrhea", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "ORF3 suppresses type I interferon response, enhancing viral replication and pathogenesis.", "protein": "ORF3 accessory protein", "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "medium", "disease": "Human coronavirus infection (HCoV-229E, NL63)", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "ORF3 inhibits human IFN\u03b2 production and signaling, facilitating immune evasion.", "protein": "ORF3 accessory protein", "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "medium", "disease": "Swine acute diarrhea syndrome", "glycan_involvement": "Glycosylation modulates host specificity.", "mechanism": "Spike protein mediates host cell entry in swine, causing diarrhea.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "medium", "disease": "Middle East respiratory syndrome (MERS)", "glycan_involvement": "Glycosylation affects receptor binding.", "mechanism": "Spike protein binds DPP4 receptor, enabling infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "low", "disease": "White-nose syndrome (WNS)", "glycan_involvement": "Not applicable.", "mechanism": "Not causal; bat populations affected by WNS are surveyed for coronavirus spike gene diversity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12033302" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Potential target for antiviral therapy due to its role in suppressing IFN response.", "protein": "ORF3 accessory protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12033302" }, { "confidence": "high", "disease": "Bat coronavirus infection", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Spike protein determines host specificity and cross-species transmission in bats.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12033302" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Extra N-acetylglucosamine branches added to N-glycans on E-cadherin.", "mechanism": "Aberrant N-glycosylation disrupts cell adhesion, promoting tumor progression.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12034019" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation by N-acetylglucosaminyltransferase V.", "mechanism": "Abnormal glycosylation weakens adhesion, facilitating metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Alters O-glycosylation patterns on proteins and possibly glycoRNAs.", "mechanism": "Dysregulated O-glycosylation enzyme linked to poor prognosis.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Adds sialic acid residues to N-glycans on proteins and glycoRNAs.", "mechanism": "Aberrant sialylation associated with tumor progression.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12034019" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation at acp3U site; sialylated glycans.", "mechanism": "Surface glycoRNA levels inversely correlate with malignancy and metastasis.", "protein": "GlycoRNAs (acp3U-modified tRNAs)", "relationship_type": "biomarker", "source_pmcid": "PMC12034019" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Sialylated glycans on glycoRNAs interact with SIGLECs.", "mechanism": "GlycoRNAs bind SIGLECs, transmitting inhibitory signals to immune cells.", "protein": "SIGLECs", "relationship_type": "causal", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Enables N-glycan linkage to RNA.", "mechanism": "Essential for acp3U formation and glycoRNA display; loss reduces glycoRNA-mediated immune modulation.", "protein": "DTWD2", "protein_enriched": { "function": "ATP-binding RNA helicase involved in the biogenesis of 60S ribosomal subunits", "gene_name": "DDX51", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N8A6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Tumor microenvironment remodeling", "glycan_involvement": "Clustered glycoRNAs with RBPs enhance glycan-mediated signaling.", "mechanism": "Surface RBPs cluster with glycoRNAs, influencing membrane organization and immune interactions.", "protein": "RNA-binding proteins (RBPs)", "relationship_type": "causal", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylated RNA epitopes recognized by antibodies.", "mechanism": "GlycoRNAs bind anti-dsRNA antibodies, suggesting involvement in autoimmunity.", "protein": "GlycoRNAs", "relationship_type": "biomarker", "source_pmcid": "PMC12034019" }, { "confidence": "medium", "disease": "Neutrophil dysfunction", "glycan_involvement": "Surface display of glycosylated RNAs mediates immune cell interactions.", "mechanism": "Cell surface glycoRNAs are essential for neutrophil recruitment and function.", "protein": "GlycoRNAs", "relationship_type": "causal", "source_pmcid": "PMC12034019" }, { "confidence": "high", "disease": "HNSCC invasion", "glycan_involvement": "GalNAc-specific glycosylation detected by WFL lectin", "mechanism": "High intratumoral ITGB1\u2013WFL associated with high T class (local invasion)", "protein": "ITGB1", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "medium", "disease": "HNSCC therapy resistance (radioresistance)", "glycan_involvement": "Fucosylation detected by UEA lectin", "mechanism": "Low serum ITGA2\u2013UEA associated with poor radiotherapy response and tumor recurrence", "protein": "ITGA2", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "low", "disease": "HNSCC distant metastasis", "glycan_involvement": "Fucosylation detected by UEA lectin", "mechanism": "High intratumoral ITGB4\u2013UEA associated with distant metastasis", "protein": "ITGB4", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "high", "disease": "HNSCC (tumor vs normal)", "glycan_involvement": "GalNAc-specific glycosylation detected by WFL", "mechanism": "ITGA3\u2013WFL discriminates tumor from normal tissue", "protein": "ITGA3", "protein_enriched": { "function": "Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma m", "gene_name": "ITGA3", "glycan_count": 98, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06247RL", "G07246CJ", "G13131HA", "G27058EU", "G30740WO", "G43223CG", "G45395BF", "G53075ES", "G57776ZS", "G60834IK", "G62765YT", "G68490OW", "G70232NH", "G70441OD", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G85282JO", "G86880BF", "G57321FI", "G49108TO", "G00912UN", "G02815KT", "G08918WF", "G10486CT", "G27947YN", "G31852PQ", "G41071NU", "G41247ZX", "G49906RN", "G59626AS", "G60033FS", "G65184UU", "G70619PT", "G72790NZ", "G83646BJ", "G87661QW", "G90659AW", "G99668VU", "G07755XJ", "G77547TA", "G47950XN", "G55132BD", "G72747WU", "G83633GK", "G85554PZ", "G06110VR", "G14669DU", "G28681TP", "G36442WJ", "G92050GC", "G37412TK", "G47702MW", "G04657PL", "G05049YU", "G05962QB", "G08290VR", "G10819WX", "G14972EH", "G16125XL", "G25079LO", "G27915IV", "G29545VG", "G30970QQ", "G35541EV", "G39471UU", "G40926MX", "G42124LM", "G47644PP", "G50856PC", "G51653BI", "G59324HL", "G64527OM", "G73291XG", "G75568BH", "G76295SF", "G80479JV", "G85677PP", "G92135MA", "G93718GY", "G98611JV", "G16407EV", "G25637MV", "G28541PG", "G37818NZ", "G43769HG", "G44753VC", "G46503DX", "G49755GI", "G57776ZU", "G70223PD", "G87123QX", "G70101JE", "G92406TI", "G01650EU", "G37399XV", "G95865ZB" ], "uniprot_id": "P26006" }, "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "medium", "disease": "HNSCC (tumor vs normal)", "glycan_involvement": "Galactose/GalNAc/sialic acid-specific glycosylation", "mechanism": "ITGA5\u2013SBA and ITGA5\u2013MAA show increased glycosylation in tumor tissue", "protein": "ITGA5", "protein_enriched": { "function": "Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct ", "gene_name": "ITGA5", "glycan_count": 121, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G00912UN", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G45395BF", "G46503DX", "G46691LC", "G55220VL", "G57776ZS", "G80075MS", "G81315DD", "G84452RH", "G90659AW", "G11629QQ", "G48905WL", "G55132BD", "G22768VO", "G09724ZC", "G64481DJ", "G83473RC", "G06356OH", "G15169WU", "G22310AV", "G31916IQ", "G47518TP", "G48414YA", "G52527GH", "G55412XP", "G10404TD", "G62765YT", "G80920RR", "G93718GY", "G02815KT", "G05049YU", "G28541PG", "G31852PQ", "G41247ZX", "G62461SM", "G72747WU", "G41891LD", "G13694XX", "G14796IU", "G33791AF", "G47748JZ", "G56784JY", "G81263BG", "G81637OR", "G89865VY", "G22573RC", "G12604EW", "G14994KB", "G18647XP", "G25703UN", "G34617SM", "G40834TG", "G41071NU", "G43223CG", "G45495MK", "G57818FI", "G59324HL", "G60033FS", "G61627IG", "G70441OD", "G70619PT", "G75568BH", "G75983OB", "G79666IR", "G87123QX", "G90382BL", "G92135MA", "G57321FI", "G06110VR", "G11041DA", "G11870QZ", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G23863VK", "G25520XG", "G29880MM", "G36191CD", "G39188ZX", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48954CA", "G50045TK", "G50489VC", "G53752TA", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G72797UR", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G90093AU", "G91365ZQ", "G91413ZX", "G91636VS", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P08648" }, "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "medium", "disease": "HNSCC (tumor vs normal)", "glycan_involvement": "Mannose-specific N-glycosylation", "mechanism": "ITGA6\u2013ConA shows increased glycosylation in tumor tissue", "protein": "ITGA6", "protein_enriched": { "function": "Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By simila", "gene_name": "ITGA6", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G18647XP", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G43769HG", "G44753VC", "G49018RC", "G49906RN", "G57776ZU", "G59626AS", "G59924QI", "G60033FS", "G61256FT", "G62765YT", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G87661QW", "G90659AW", "G92050GC", "G04657PL", "G05049YU", "G06356OH", "G11314AS", "G12313PD", "G23863VK", "G25451PN", "G42124LM", "G45395BF", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G60834IK", "G72797UR", "G79666IR", "G80223IX", "G80479JV", "G81263BG", "G84452RH", "G87123QX", "G93718GY", "G95865ZB", "G96577RX", "G20210JR", "G29299MO", "G92406TI", "G08290VR", "G25079LO", "G46503DX", "G48584BU", "G62894KT", "G73968GN" ], "uniprot_id": "P23229" }, "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "medium", "disease": "HNSCC stemness/invasion", "glycan_involvement": "GalNAc-specific glycosylation", "mechanism": "ITGB1\u2013WFL associated with stemness and local aggressiveness", "protein": "ITGB1", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "low", "disease": "HNSCC field carcinogenesis", "glycan_involvement": "Fucosylation (UEA/AAL)", "mechanism": "ITGA2 glycosylation associated with field cancerization", "protein": "ITGA2", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "low", "disease": "HNSCC tumor recurrence", "glycan_involvement": "Sialic acid-specific glycosylation (MAA)", "mechanism": "Low serum ITGB4\u2013MAA associated with tumor recurrence (limited by low S/B)", "protein": "ITGB4", "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "low", "disease": "HNSCC metastasis", "glycan_involvement": "Not specified in this study", "mechanism": "High intratumoral ITGA3 expression previously linked to lymphatic metastasis", "protein": "ITGA3", "protein_enriched": { "function": "Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma m", "gene_name": "ITGA3", "glycan_count": 98, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06247RL", "G07246CJ", "G13131HA", "G27058EU", "G30740WO", "G43223CG", "G45395BF", "G53075ES", "G57776ZS", "G60834IK", "G62765YT", "G68490OW", "G70232NH", "G70441OD", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G85282JO", "G86880BF", "G57321FI", "G49108TO", "G00912UN", "G02815KT", "G08918WF", "G10486CT", "G27947YN", "G31852PQ", "G41071NU", "G41247ZX", "G49906RN", "G59626AS", "G60033FS", "G65184UU", "G70619PT", "G72790NZ", "G83646BJ", "G87661QW", "G90659AW", "G99668VU", "G07755XJ", "G77547TA", "G47950XN", "G55132BD", "G72747WU", "G83633GK", "G85554PZ", "G06110VR", "G14669DU", "G28681TP", "G36442WJ", "G92050GC", "G37412TK", "G47702MW", "G04657PL", "G05049YU", "G05962QB", "G08290VR", "G10819WX", "G14972EH", "G16125XL", "G25079LO", "G27915IV", "G29545VG", "G30970QQ", "G35541EV", "G39471UU", "G40926MX", "G42124LM", "G47644PP", "G50856PC", "G51653BI", "G59324HL", "G64527OM", "G73291XG", "G75568BH", "G76295SF", "G80479JV", "G85677PP", "G92135MA", "G93718GY", "G98611JV", "G16407EV", "G25637MV", "G28541PG", "G37818NZ", "G43769HG", "G44753VC", "G46503DX", "G49755GI", "G57776ZU", "G70223PD", "G87123QX", "G70101JE", "G92406TI", "G01650EU", "G37399XV", "G95865ZB" ], "uniprot_id": "P26006" }, "relationship_type": "biomarker", "source_pmcid": "PMC12034151" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Transports UDP-galactose for glycosylation in Golgi; altered glycosylation affects cell adhesion, immune evasion, and drug response.", "mechanism": "Upregulation promotes tumor progression via MYC-mediated metabolic reprogramming, increases proliferation, metastasis, and chemoresistance to irinotecan.", "protein": "SLC35A2", "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12035830" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation changes modulate cell surface properties and immune cell infiltration.", "mechanism": "High expression predicts poor relapse-free survival and resistance to irinotecan.", "protein": "SLC35A2", "relationship_type": "biomarker", "source_pmcid": "PMC12035830" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation alters tumor microenvironment and immune recognition.", "mechanism": "High SLC35A2 reduces infiltration of cytotoxic CD8+ T cells and B cells, contributing to immune evasion.", "protein": "SLC35A2", "relationship_type": "causal", "source_pmcid": "PMC12035830" }, { "confidence": "high", "disease": "SLC35A2-CDG", "glycan_involvement": "Defective UDP-galactose transport impairs glycoprotein biosynthesis.", "mechanism": "Mutations cause congenital disorder of glycosylation with neurological symptoms.", "protein": "SLC35A2", "relationship_type": "causal", "source_pmcid": "PMC12035830" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation II (CDG II)", "glycan_involvement": "Impaired sialylation of glycoproteins.", "mechanism": "Mutations lead to defective CMP-sialic acid transport and abnormal sialylation.", "protein": "SLC35A1", "relationship_type": "causal", "source_pmcid": "PMC12035830" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Sialylation may influence immune cell activity and tumor invasion.", "mechanism": "Downregulation in CRC; higher methylation; positive correlation with CD8+ T cell infiltration.", "protein": "SLC35A1", "relationship_type": "protective", "source_pmcid": "PMC12035830" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "UDP-GlcNAc transport affects glycosylation and immune microenvironment.", "mechanism": "Higher expression associated with better relapse-free survival and increased immune infiltration.", "protein": "SLC35A3", "relationship_type": "protective", "source_pmcid": "PMC12035830" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation changes promote tumor progression.", "mechanism": "High expression linked to poor recurrence-free survival and ERK pathway activation.", "protein": "SLC35A2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12035830" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "UDP-galactose transport supports complex glycan assembly.", "mechanism": "Promotes metastasis via regulation of cellular glycosylation and galactosyltransferase recruitment.", "protein": "SLC35A2", "relationship_type": "causal", "source_pmcid": "PMC12035830" }, { "confidence": "medium", "disease": "Pancreatic ductal carcinoma", "glycan_involvement": "UDP-GlcNAc transport influences glycosylation and metabolism.", "mechanism": "Upregulation affects glycolysis and is associated with prognosis.", "protein": "SLC35A3", "relationship_type": "causal", "source_pmcid": "PMC12035830" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for stability and secretion.", "mechanism": "FSTL3 neutralizes activins/TGF\u03b2s/GDF11, increased levels indicate heightened TGF\u03b2 signaling and maladaptive remodeling.", "protein": "FSTL3", "protein_enriched": { "function": "Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such as activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellula", "gene_name": "FSTL3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G43769HG" ], "uniprot_id": "O95633" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Strongly associated with aging, frailty, and HF; upregulated in injury, promotes endothelial senescence and fibrosis.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation impacts receptor interaction.", "mechanism": "Activin A increases with age and HF; inhibition improves cardiac function/remodeling in models.", "protein": "Activin A", "protein_enriched": { "function": "Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythr", "gene_name": "INHBA", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G70994MS" ], "uniprot_id": "P08476" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Transmembrane glycoprotein; N-glycosylation modulates ligand binding and receptor stability.", "mechanism": "ErbB1 signaling is negatively associated with aging/HF; downregulation leads to dysfunction, activation improves cardiac outcomes.", "protein": "ErbB1 (EGFR)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for receptor interaction.", "mechanism": "NRG1/ErbB signaling promotes cardiomyocyte survival, regeneration, and function; recombinant NRG1 improves HF in trials.", "protein": "NRG1", "protein_enriched": { "function": "Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB rece", "gene_name": "NRG1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q02297" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12036312" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Membrane glycoprotein; glycosylation affects cell surface expression.", "mechanism": "TREM1 is associated with inflammation in aging and frailty; part of SASP signature.", "protein": "TREM1", "protein_enriched": { "function": "Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses (PubMed:10799849, PubMed:21393102). Upon activation by various ligands such as PGL", "gene_name": "TREM1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9NP99" }, "relationship_type": "biomarker", "source_pmcid": "PMC12036312" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation impacts stability.", "mechanism": "IGFBP7 is linked to insulin/growth signaling dysregulation in aging and HF.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "biomarker", "source_pmcid": "PMC12036312" }, { "confidence": "medium", "disease": "Cardiac Fibrosis", "glycan_involvement": "Secreted glycoprotein; glycosylation required for activity.", "mechanism": "TIMP1 is associated with fibrosis in aging and HF; regulates extracellular matrix turnover.", "protein": "TIMP1", "relationship_type": "biomarker", "source_pmcid": "PMC12036312" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation modulates receptor binding.", "mechanism": "ANGPT2 involved in vasculogenesis and vascular remodeling in aging and HF.", "protein": "ANGPT2", "protein_enriched": { "function": "Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling (PubMed:15284220, PubMed:19116766, PubMed:19223473, PubMed:9204896). Can induce tyrosine phosphorylation of TE", "gene_name": "ANGPT2", "glycan_count": 23, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G05962QB", "G30221QT", "G35541EV", "G62765YT", "G80479JV", "G81637OR", "G82443XX", "G93718GY", "G02815KT", "G10486CT", "G27058EU", "G41071NU", "G42124LM", "G45395BF", "G46691LC", "G68735SN", "G70619PT", "G90659AW", "G20956ZV", "G74724QE", "G34989PA", "G98611JV", "G49108TO" ], "uniprot_id": "O15123" }, "relationship_type": "biomarker", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and detection.", "mechanism": "NTproBNP is a clinical biomarker for HF, consistently elevated in aging and frailty.", "protein": "NTproBNP", "relationship_type": "biomarker", "source_pmcid": "PMC12036312" }, { "confidence": "high", "disease": "Moyamoya Disease (MMD)", "glycan_involvement": "Decreased sialylation, galactosylation, fucosylation; increased bisecting GlcNAc.", "mechanism": "Altered IgG N-glycosylation modulates inflammatory response, contributing to MMD pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "high", "disease": "Moyamoya Disease (MMD)", "glycan_involvement": "GP21 decrease; sialylation loss enhances pro-inflammatory signaling.", "mechanism": "GP21 (sialylated glycan) reduction is strongly associated with increased MMD risk and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Decreased galactosylation/sialylation; increased bisecting GlcNAc.", "mechanism": "Reduced galactosylation and sialylation, increased bisecting GlcNAc linked to chronic inflammation in IS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Decreased galactosylation/sialylation.", "mechanism": "Altered IgG glycosylation (decreased galactosylation/sialylation) associated with neuroinflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Decreased galactosylation/fucosylation.", "mechanism": "Reduced galactosylation and fucosylation linked to increased inflammatory activity in SLE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Decreased galactosylation/sialylation.", "mechanism": "Decreased galactosylation and sialylation associated with UC inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Crohn\u2019s Disease (CD)", "glycan_involvement": "Decreased galactosylation/sialylation.", "mechanism": "Lower galactosylation and sialylation linked to chronic inflammation in CD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Decreased galactosylation/sialylation.", "mechanism": "Reduced galactosylation and sialylation in IgG N-glycans associated with RA severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Decreased galactosylation; increased bisecting GlcNAc.", "mechanism": "Altered IgG glycosylation (decreased galactosylation, increased bisecting GlcNAc) linked to CKD inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "medium", "disease": "Hypertension (HT)", "glycan_involvement": "Decreased galactosylation; increased bisecting GlcNAc.", "mechanism": "Reduced galactosylation and increased bisecting GlcNAc associated with pro-inflammatory state in HT.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12036608" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "High N-glycosylation at Fab region; sialylation measured.", "mechanism": "Elevated Fab glycosylation (>80% in anti-CCP) linked to disease progression and development.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Complex-type N-glycans, high sialylation.", "mechanism": "Fab glycosylation of anti-CCP autoantibodies predicts disease development.", "protein": "Anti-CCP IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "Pemphigus vulgaris (PV)", "glycan_involvement": "N-glycosylation at Fab region, high sialylation.", "mechanism": "Elevated Fab glycosylation in anti-Dsg3 autoantibodies observed in PV.", "protein": "Anti-Dsg3 IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "N-glycosylation at Fab region, high sialylation.", "mechanism": "Fab glycosylation of anti-PR3 autoantibodies elevated and increases during B cell depletion therapy.", "protein": "Anti-PR3 IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "Pemphigus vulgaris (PV)", "glycan_involvement": "N-glycosylation, sialylation measured.", "mechanism": "Total IgG Fab glycosylation modestly decreases after B cell depletion therapy.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "N-glycosylation, sialylation measured.", "mechanism": "Total IgG Fab glycosylation increases after B cell depletion therapy.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "N-glycosylation, sialylation measured.", "mechanism": "No change in Fab glycosylation of total IgG after B cell depletion therapy.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12037893" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "CD20 is a glycoprotein target for monoclonal antibody therapy.", "mechanism": "Targeted by rituximab/ocrelizumab for B cell depletion.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "N-glycosylation at variable domain, alters antigen binding and B cell survival.", "mechanism": "Fab glycosylation may enhance BCR signaling, contributing to autoimmunity.", "protein": "IgG Fab region", "relationship_type": "causal", "source_pmcid": "PMC12037893" }, { "confidence": "medium", "disease": "Pemphigus vulgaris (PV)", "glycan_involvement": "N-glycosylation at Fab region, affects B cell tolerance checkpoints.", "mechanism": "Fab glycosylation may provide survival advantage to autoreactive B cells.", "protein": "IgG Fab region", "relationship_type": "causal", "source_pmcid": "PMC12037893" }, { "confidence": "high", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and immune interactions.", "mechanism": "Blockade by pembrolizumab leads to immune-mediated endothelial injury and inflammation, causing PAH.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "PD-L1 glycosylation modulates immune recognition and therapeutic efficacy.", "mechanism": "Tumor-induced PD-L1 expression; inhibition by ICI increases immune toxicity, contributing to PAH.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Immune-mediated adverse events", "glycan_involvement": "CTLA-4 glycosylation regulates surface expression and function.", "mechanism": "ICI targeting CTLA-4 disrupts immune tolerance, increasing risk of immune-mediated tissue damage.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC12045750" }, { "confidence": "high", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "Antagonism by macitentan reduces vasoconstriction and fibrosis in PAH.", "protein": "Endothelin receptor type A/B", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "IL-12 is glycosylated, influencing secretion and stability.", "mechanism": "Elevated IL-12 promotes inflammatory-mediated PAH; reduced by B-cell depletion.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "IL-17 drives inflammation and vascular remodeling in PAH.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal", "source_pmcid": "PMC12045750" }, { "confidence": "high", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "BNP is glycosylated, affecting its half-life and detection.", "mechanism": "BNP levels reflect right ventricular strain and PAH severity.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "IgG glycosylation modulates effector function and immune response.", "mechanism": "Autoantibodies (IgG) are used to exclude autoimmune causes of PAH.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "CK-7 is a glycoprotein; glycosylation may affect detection.", "mechanism": "CK-7 positivity aids in lung adenocarcinoma diagnosis.", "protein": "CK-7", "relationship_type": "biomarker", "source_pmcid": "PMC12045750" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "TTF-1 is glycosylated, influencing nuclear localization and function.", "mechanism": "TTF-1 positivity supports diagnosis of lung adenocarcinoma.", "protein": "TTF-1", "relationship_type": "biomarker", "source_pmcid": "PMC12045750" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects stability and receptor interaction.", "mechanism": "Anti-TNF-\u03b1 antibodies reduce inflammation by neutralizing TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045780" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "IL-12 is glycosylated, which is important for secretion and activity.", "mechanism": "Anti-IL-12 antibodies block pro-inflammatory signaling.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045780" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "IL-23 glycosylation is required for secretion and function.", "mechanism": "Anti-IL-23 antibodies inhibit Th17-mediated inflammation.", "protein": "IL-23", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045780" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Integrins are glycoproteins; glycosylation modulates cell adhesion.", "mechanism": "Anti-integrin \u03b14\u03b27 antibodies block lymphocyte homing to gut.", "protein": "Integrin \u03b14\u03b27", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "JAK1 is glycosylated; glycosylation may affect stability and localization.", "mechanism": "JAK1 inhibition suppresses cytokine signaling in T cells.", "protein": "JAK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Some STATs are glycosylated, influencing nuclear translocation.", "mechanism": "STAT activation drives pro-inflammatory gene expression.", "protein": "STAT proteins", "relationship_type": "causal", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "IL-6 glycosylation is required for secretion and receptor binding.", "mechanism": "IL-6 promotes inflammation and is elevated in active disease.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "IL-8 is glycosylated, affecting chemotactic activity.", "mechanism": "IL-8 recruits neutrophils to inflamed tissue.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "causal", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 is a key mediator of inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12045780" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "IL-10 glycosylation is important for stability and function.", "mechanism": "IL-10 is anti-inflammatory and regulates immune response.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12045780" }, { "confidence": "high", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation affects ALP stability and serum half-life.", "mechanism": "Elevated serum ALP indicates cholestasis due to bile duct obstruction by stones.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12045936" }, { "confidence": "high", "disease": "Biliary obstruction", "glycan_involvement": "N-glycosylation modulates ALP secretion.", "mechanism": "ALP is released from biliary epithelium during obstruction.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12045936" }, { "confidence": "medium", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Elevated AST reflects hepatocellular injury secondary to bile duct obstruction.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12045936" }, { "confidence": "medium", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "ALT elevation signals hepatocyte damage from biliary obstruction.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12045936" }, { "confidence": "medium", "disease": "Biliary obstruction", "glycan_involvement": "Albumin glycosylation can alter bilirubin binding.", "mechanism": "Increased serum bilirubin (direct and indirect) indicates impaired bile flow.", "protein": "Bilirubin-albumin complex", "relationship_type": "biomarker", "source_pmcid": "PMC12045936" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation of G protein is critical for proper folding, antigenicity, and immune recognition.", "mechanism": "Essential for viral entry into host cells and neuroinvasiveness; mediates attachment and membrane fusion.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "causal", "source_pmcid": "PMC12046086" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects immunogenicity and vaccine efficacy.", "mechanism": "Targeted by neutralizing antibodies induced by vaccination; mutations at key sites reduce pathogenicity.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046086" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation sites maintain conformational epitopes for antibody binding.", "mechanism": "Induction of neutralizing antibodies against G protein confers protective immunity.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "protective", "source_pmcid": "PMC12046086" }, { "confidence": "medium", "disease": "Chronic skin disease (post-vaccine exposure)", "glycan_involvement": "Glycoprotein expression in vector may influence host immune response.", "mechanism": "Exposure to recombinant vaccinia virus expressing G protein (V-RG vaccine) associated with rare chronic skin disease in humans.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "causal", "source_pmcid": "PMC12046086" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation status preserved after mutation, maintaining immunogenicity.", "mechanism": "Amino acid substitutions at positions 194 and 333 in G protein reduce pathogenicity and prevent reversion to virulence.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "protective", "source_pmcid": "PMC12046086" }, { "confidence": "high", "disease": "Invasive pneumococcal disease", "glycan_involvement": "Polysaccharide capsule is glycan-based, critical for pathogenicity and vaccine target.", "mechanism": "Capsular polysaccharide is main virulence factor, mediates immune evasion and serotype classification.", "protein": "S. pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Invasive meningococcal disease", "glycan_involvement": "Polysaccharide capsule is glycan-based, essential for virulence and vaccine design.", "mechanism": "Capsular polysaccharide enables immune evasion and serogroup classification; target for conjugate vaccines.", "protein": "N. meningitidis capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Herpes zoster", "glycan_involvement": "Glycoprotein E is glycosylated, enhancing immunogenicity and vaccine efficacy.", "mechanism": "Recombinant zoster vaccine uses glycoprotein E to elicit protective immunity.", "protein": "VZV glycoprotein E", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune recognition and vaccine response.", "mechanism": "Spike glycoprotein is the antigen in mRNA and viral vector vaccines, inducing neutralizing antibodies.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects antigenicity and immune response.", "mechanism": "Haemagglutinin is the major antigen in inactivated and live-attenuated vaccines.", "protein": "Influenza haemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Cervical cancer (HPV-related)", "glycan_involvement": "L1 protein forms VLPs; glycosylation may affect assembly and immunogenicity.", "mechanism": "Virus-like particle vaccines use L1 protein to induce immunity against high-risk HPV types.", "protein": "HPV L1 protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Dengue illness", "glycan_involvement": "Glycosylation modulates antigenicity and immune response.", "mechanism": "Envelope glycoprotein is the main antigen in live-attenuated dengue vaccines.", "protein": "DENV envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046087" }, { "confidence": "medium", "disease": "Invasive meningococcal disease", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Used in MenB vaccines to induce protective immunity.", "protein": "Human factor H binding protein (N. meningitidis)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8KQF6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Pneumococcal pneumonia", "glycan_involvement": "Glycan capsule is essential for virulence and vaccine targeting.", "mechanism": "Capsular polysaccharide mediates lung infection and immune evasion.", "protein": "S. pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Community-acquired bacterial meningitis", "glycan_involvement": "Glycan capsule is critical for pathogenesis and vaccine efficacy.", "mechanism": "Capsular polysaccharide enables CNS invasion and immune evasion.", "protein": "N. meningitidis capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12046087" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "F protein is a glycoprotein; glycosylation is required for proper folding and function.", "mechanism": "F protein mediates fusion of viral and host cell membranes, enabling viral entry and infection.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "HN is a glycoprotein; glycosylation is important for receptor binding.", "mechanism": "HN protein binds to sialic acid receptors on host cells, facilitating viral attachment and release.", "protein": "Hemagglutinin-neuraminidase (HN) protein", "relationship_type": "causal", "source_pmcid": "PMC12046092" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation of F protein is necessary for infectivity.", "mechanism": "F protein-mediated viral entry leads to lower respiratory tract infection and pneumonia.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC12046092" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation supports HN function in host interaction.", "mechanism": "HN protein enables viral attachment to airway epithelial cells, contributing to bronchiolitis.", "protein": "Hemagglutinin-neuraminidase (HN) protein", "relationship_type": "causal", "source_pmcid": "PMC12046092" }, { "confidence": "medium", "disease": "Chronic respiratory disease exacerbation", "glycan_involvement": "Glycosylation maintains F protein stability and infectivity.", "mechanism": "F protein-driven HMPV infection can worsen pre-existing chronic respiratory diseases.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "Glycosylation may affect epitope exposure and antibody binding.", "mechanism": "Neutralizing antibodies against F protein prevent viral entry and infection.", "protein": "Fusion (F) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Antibodies against HN protein block viral attachment and release.", "protein": "Hemagglutinin-neuraminidase (HN) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "Glycosylation status may influence vaccine efficacy.", "mechanism": "Vaccine-induced immunity targeting F protein provides protection against HMPV.", "protein": "Fusion (F) protein", "relationship_type": "protective", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "Glycosylation may affect antigenicity and immune response.", "mechanism": "Vaccines targeting HN protein elicit neutralizing antibodies, reducing infection risk.", "protein": "Hemagglutinin-neuraminidase (HN) protein", "relationship_type": "protective", "source_pmcid": "PMC12046092" }, { "confidence": "medium", "disease": "Human metapneumovirus (HMPV) infection", "glycan_involvement": "Glycosylation may influence serological detection.", "mechanism": "Presence of anti-F antibodies indicates prior exposure or vaccine response.", "protein": "Fusion (F) protein", "relationship_type": "biomarker", "source_pmcid": "PMC12046092" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Gper1 is a glycosylated membrane receptor; glycosylation may affect receptor localization and signaling.", "mechanism": "High Gper1 expression in CRC tumor tissue (especially in males) is associated with worse survival, particularly in early-stage disease without nodal involvement.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "biomarker", "source_pmcid": "PMC12046377" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation may modulate Gper1's interaction with ligands and downstream signaling.", "mechanism": "Gper1 upregulation promotes oncogenic signaling via EGFR and VEGFA, contributing to tumor progression, especially when p53 is mutated.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "causal", "source_pmcid": "PMC12046377" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation may influence Gper1's cell surface expression and function.", "mechanism": "Gper1 exerts tumor suppressor effects in CRC cells with wild-type p53 (e.g., LoVo cells), reducing metabolic rate and possibly inhibiting proliferation.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "protective", "source_pmcid": "PMC12046377" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "ESR2 is glycosylated; glycosylation may affect receptor stability and transcriptional activity.", "mechanism": "ESR2 mediates beneficial effects of estradiol, with higher ESR2 expression linked to reduced CRC incidence and tumorigenesis.", "protein": "ESR2 (Estrogen receptor beta)", "relationship_type": "protective", "source_pmcid": "PMC12046377" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "EGFR glycosylation is critical for ligand binding and receptor activation.", "mechanism": "EGFR is activated downstream of Gper1 signaling; EGFR inhibitors (e.g., Cetuximab, Panitumumab) are effective in CRC treatment.", "protein": "EGFR (Epidermal growth factor receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046377" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "VEGFA glycosylation affects secretion and receptor binding.", "mechanism": "Gper1 upregulation correlates with increased VEGFA expression, promoting angiogenesis and tumor progression.", "protein": "VEGFA (Vascular endothelial growth factor A)", "relationship_type": "causal", "source_pmcid": "PMC12046377" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "FASN is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Gper1 activation induces FASN expression via EGFR/ERK/AP1 pathway, promoting CRC progression.", "protein": "FASN (Fatty acid synthase)", "protein_enriched": { "function": "Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This mu", "gene_name": "FASN", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G36379GD", "G32392SM", "G72065MN" ], "uniprot_id": "P49327" }, "relationship_type": "causal", "source_pmcid": "PMC12046377" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect Gper1's pharmacological response.", "mechanism": "Gper1 agonists (e.g., LNS8801) show beneficial effects in melanoma patients, suggesting a tumor suppressor role.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "protective", "source_pmcid": "PMC12046377" }, { "confidence": "low", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation may modulate receptor function.", "mechanism": "Gper1 implicated as a tumor suppressor in pancreatic cancer.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "protective", "source_pmcid": "PMC12046377" }, { "confidence": "low", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation may influence Gper1's oncogenic signaling.", "mechanism": "Gper1 acts as a tumor promoter in glioblastoma.", "protein": "Gper1 (G protein-coupled estrogen receptor 1)", "protein_enriched": { "function": "G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP pro", "gene_name": "GPER1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99527" }, "relationship_type": "causal", "source_pmcid": "PMC12046377" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation of beta-2-glycoprotein-1 affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2-glycoprotein-1 promote thrombosis.", "protein": "beta-2-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC12047565" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Targets glycoprotein complexes; glycosylation may affect epitope exposure.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12047565" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation may modulate binding.", "mechanism": "Lupus anticoagulant positivity is used in APS diagnosis and risk stratification.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12047565" }, { "confidence": "high", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation influences immune recognition and thrombogenicity.", "mechanism": "Autoantibodies against beta-2-glycoprotein-1 increase risk of DVT in APS.", "protein": "beta-2-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC12047565" }, { "confidence": "high", "disease": "Pulmonary embolism (PE)", "glycan_involvement": "Glycosylation modulates autoantibody binding and pathogenicity.", "mechanism": "Autoantibodies promote thrombosis leading to PE in APS.", "protein": "beta-2-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC12047565" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may affect immunogenicity in SLE context.", "mechanism": "Anti-beta-2-glycoprotein-1 antibodies are common in SLE and indicate APS risk.", "protein": "beta-2-glycoprotein-1", "relationship_type": "biomarker", "source_pmcid": "PMC12047565" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation affects stability and serum levels.", "mechanism": "Alpha-1 antitrypsin levels are measured to exclude hereditary liver disease in AFLP differential diagnosis.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Ceruloplasmin levels are measured to exclude Wilson's disease in AFLP differential diagnosis.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Antibodies to tissue transglutaminase are measured to exclude autoimmune hepatitis in AFLP differential diagnosis.", "protein": "Tissue transglutaminase", "protein_enriched": { "function": "Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono-", "gene_name": "TGM2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21980" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation required for secretion and clotting function.", "mechanism": "Fibrinogen levels reflect hepatic synthetic function in AFLP.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation modulates immune function.", "mechanism": "IgA levels measured to exclude autoimmune hepatitis in AFLP differential diagnosis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation modulates immune function.", "mechanism": "IgG levels measured to exclude autoimmune hepatitis in AFLP differential diagnosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Glycosylation essential for function.", "mechanism": "Low fibrinogen indicates impaired hepatic synthesis in liver failure.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Glycosylation affects serum levels.", "mechanism": "Normal alpha-1 antitrypsin excludes genetic deficiency as cause of liver failure.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Normal ceruloplasmin excludes Wilson's disease as cause of liver failure.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048149" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Not a glycoprotein, but influences glycoprotein secretion via bile acid pathways.", "mechanism": "Ursodiol is used to treat ICP by improving bile flow; indirectly affects glycoprotein metabolism.", "protein": "Ursodeoxycholic acid (Ursodiol)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048149" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies target beta-2 glycoprotein I, leading to increased thrombosis risk.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12048177" }, { "confidence": "high", "disease": "Catastrophic antiphospholipid syndrome (CAPS)", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "Autoantibodies against beta-2 glycoprotein I drive rapid, multi-organ thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12048177" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation may affect epitope exposure.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS.", "protein": "anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12048177" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycoprotein complexes; glycosylation may influence antibody binding.", "mechanism": "Lupus anticoagulant antibodies are diagnostic and predictive of thrombosis.", "protein": "lupus anticoagulant antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12048177" }, { "confidence": "medium", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation modulates immune response and thrombogenicity.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote venous thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12048177" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation may affect protein-protein interactions in clot formation.", "mechanism": "Autoantibody-mediated activation of coagulation via beta-2 glycoprotein I.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12048177" }, { "confidence": "medium", "disease": "Multiple organ infarcts (kidney, liver, spleen)", "glycan_involvement": "Glycosylation influences immune complex formation and tissue targeting.", "mechanism": "Autoantibodies induce microvascular thrombosis in multiple organs.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12048177" }, { "confidence": "high", "disease": "Catastrophic antiphospholipid syndrome (CAPS)", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may modulate antigenicity.", "mechanism": "Presence of lupus anticoagulant is diagnostic for CAPS and correlates with severity.", "protein": "lupus anticoagulant antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12048177" }, { "confidence": "medium", "disease": "Catastrophic antiphospholipid syndrome (CAPS)", "glycan_involvement": "Targets glycoprotein antigens; glycosylation may affect antibody binding.", "mechanism": "High titers are associated with CAPS diagnosis and severity.", "protein": "anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12048177" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation may influence therapeutic efficacy and immune clearance.", "mechanism": "Targeted by immunomodulatory therapies (e.g., IVIG, plasmapheresis) to reduce autoantibody effects.", "protein": "beta-2 glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048177" }, { "confidence": "high", "disease": "Cervical intraepithelial neoplasia (CIN)", "glycan_involvement": "CD44 is a heavily glycosylated cell surface protein; glycosylation modulates its role in cell adhesion, migration, and EMT.", "mechanism": "CD44 overexpression correlates with higher CIN grade, indicating aggressive epithelial transformation and tumor progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12049178" }, { "confidence": "high", "disease": "Immature polypoid squamous metaplasia (IPM)", "glycan_involvement": "Glycosylation of CD44 affects its interaction with extracellular matrix and cell signaling.", "mechanism": "Moderate CD44 expression in IPM predicts risk of progression to CIN; strong expression in progressive IPM cases.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Altered glycosylation of CD44 may enhance metastatic behavior.", "mechanism": "CD44 overexpression is associated with increased tumor aggressiveness, EMT, and metastatic potential.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12049178" }, { "confidence": "high", "disease": "Cervical intraepithelial neoplasia (CIN)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "P16 upregulation is strongly associated with high-grade CIN and high-risk HPV infection.", "protein": "P16", "protein_enriched": { "function": "Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblas", "gene_name": "CDKN2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049178" }, { "confidence": "high", "disease": "Immature polypoid squamous metaplasia (IPM)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Moderate or strong P16 expression in IPM predicts progression to CIN2/3.", "protein": "P16", "protein_enriched": { "function": "Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblas", "gene_name": "CDKN2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Cervical intraepithelial neoplasia (CIN)", "glycan_involvement": "Targeting glycosylation of CD44 may modulate its function.", "mechanism": "CD44's role in cell adhesion and migration makes it a potential target for inhibiting CIN progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Immature polypoid squamous metaplasia (IPM)", "glycan_involvement": "Glycosylation status could affect therapeutic efficacy.", "mechanism": "CD44 may be targeted to prevent progression of IPM to CIN.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation modulates CD44-mediated cell migration.", "mechanism": "CD44 is implicated in metastasis; targeting its glycosylation may reduce invasiveness.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Cervical intraepithelial neoplasia (CIN)", "glycan_involvement": "Glycosylation is essential for CD44 function in disease.", "mechanism": "CD44-mediated cell adhesion and migration contribute to epithelial transformation and CIN progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12049178" }, { "confidence": "medium", "disease": "Immature polypoid squamous metaplasia (IPM)", "glycan_involvement": "Glycosylation regulates CD44's role in EMT.", "mechanism": "CD44 expression facilitates transition from IPM to CIN via enhanced cell migration and EMT.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12049178" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antibody stability and immune recognition.", "mechanism": "ANA is a diagnostic marker for SLE, indicating autoimmune activity.", "protein": "Anti-nuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "Anti-dsDNA is highly specific for SLE and correlates with disease activity.", "protein": "Anti-double stranded DNA antibody (anti-dsDNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation influences antibody solubility and immune complex formation.", "mechanism": "Anti-Smith antibody is specific for SLE diagnosis.", "protein": "Anti-Smith antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "medium", "disease": "Lupus hepatitis", "glycan_involvement": "Glycosylation may affect antibody-antigen interactions in hepatic tissue.", "mechanism": "Anti-ribosomal P antibody is associated with lupus hepatitis, a hepatic manifestation of SLE.", "protein": "Anti-ribosomal P antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation is essential for C3 function and stability.", "mechanism": "C3 levels reflect SLE activity; low levels indicate active disease.", "protein": "C3 complement", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation is required for complement activation.", "mechanism": "C4 levels are used to monitor SLE activity.", "protein": "C4 complement", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects ferritin secretion and stability.", "mechanism": "Elevated ferritin reflects acute liver injury and inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Surface glycoproteins mediate cell-cell interactions and immune response.", "mechanism": "Kupffer cell activation contributes to hepatic inflammation in DILI.", "protein": "Kupffer cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12049183" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects CK7 localization and function.", "mechanism": "CK7 immunostaining highlights bile duct injury and ductular reaction in DILI.", "protein": "CK7 (Cytokeratin 7)", "relationship_type": "biomarker", "source_pmcid": "PMC12049183" }, { "confidence": "medium", "disease": "Primary biliary cholangitis", "glycan_involvement": "Aberrant glycosylation may trigger autoimmunity.", "mechanism": "Autoimmune attack on bile duct glycoproteins leads to cholangitis.", "protein": "Bile duct glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12049183" }, { "confidence": "high", "disease": "hypercoagulable state", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2-glycoprotein I are associated with increased risk of thrombosis.", "protein": "beta-2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "high", "disease": "hypercoagulable state", "glycan_involvement": "Targets glycoprotein complexes; glycosylation modulates immune recognition.", "mechanism": "Presence indicates antiphospholipid syndrome, increasing risk for arterial and venous thrombosis.", "protein": "anticardiolipin antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "high", "disease": "hypercoagulable state", "glycan_involvement": "N-glycosylation influences factor V stability and function.", "mechanism": "Factor V Leiden mutation increases risk of thrombosis.", "protein": "factor V", "relationship_type": "causal", "source_pmcid": "PMC12049185" }, { "confidence": "high", "disease": "hypercoagulable state", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation modulates antigenicity.", "mechanism": "Autoantibodies interfere with phospholipid-dependent coagulation, increasing thrombosis risk.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "high", "disease": "acute limb ischemia", "glycan_involvement": "Glycosylation affects tPA stability and activity.", "mechanism": "tPA is used for thrombolysis to restore perfusion in ALI.", "protein": "tissue plasminogen activator (tPA)", "protein_enriched": { "function": "Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tiss", "gene_name": "PLAT", "glycan_count": 111, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G01769FS", "G06110VR", "G09482NW", "G12398HZ", "G13151XE", "G21415RL", "G24440EI", "G35808UX", "G39188ZX", "G40702WU", "G41304KE", "G44533KV", "G44842OK", "G48848IF", "G55220VL", "G68668TB", "G68758PE", "G77038WW", "G77964WB", "G80966KZ", "G83161QT", "G83461WR", "G85542KD", "G88417ED", "G88461FF", "G92570PJ", "G94141FZ", "G95861KV", "G96063MG", "G97832IV", "G00463XD", "G02000AU", "G04657PL", "G05813WO", "G06330RB", "G06772YH", "G08110WX", "G11629QQ", "G13456GP", "G15169WU", "G17689DH", "G22310AV", "G24511TX", "G26076FX", "G26915XM", "G27058EU", "G29972ZX", "G37022BP", "G39172SO", "G43814TV", "G45209NR", "G46691LC", "G47108UC", "G50757KG", "G58481XO", "G62765SF", "G69834CE", "G70511VE", "G72667IM", "G81198YO", "G82779CI", "G88027AL", "G91413ZX", "G91905FJ", "G92617LF", "G93860XO", "G94531EZ", "G94974XB", "G97428EW", "G98259QP", "G42124LM", "G45395BF", "G53854XZ", "G74724QE", "G57321FI", "G96881BQ", "G00155YT", "G01629KW", "G03382KH", "G05724UK", "G10256JP", "G13728QT", "G14260UH", "G17276XO", "G23294PN", "G23432EQ", "G23863VK", "G26034OB", "G27696FL", "G41917DR", "G44121LY", "G44444MB", "G45661NA", "G45981GB", "G46665ZP", "G49108TO", "G50045TK", "G53752TA", "G64527OM", "G74239ZQ", "G78059CC", "G81263BG", "G82463GQ", "G83386PJ", "G84452RH", "G85194VU", "G85618VM", "G92081HT", "G93683YO", "G96416FQ", "G98481KT" ], "uniprot_id": "P00750" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049185" }, { "confidence": "medium", "disease": "pulmonary embolism", "glycan_involvement": "N-glycosylation modulates prothrombin activation.", "mechanism": "Prothrombin is central to thrombus formation in PE.", "protein": "prothrombin", "relationship_type": "causal", "source_pmcid": "PMC12049185" }, { "confidence": "medium", "disease": "deep vein thrombosis", "glycan_involvement": "Glycosylation affects fibrinogen polymerization and clot structure.", "mechanism": "Fibrinogen is converted to fibrin, forming the structural basis of thrombi.", "protein": "fibrinogen", "relationship_type": "causal", "source_pmcid": "PMC12049185" }, { "confidence": "medium", "disease": "occult malignancy", "glycan_involvement": "CEA is highly glycosylated; glycan patterns affect detection and immune response.", "mechanism": "Elevated CEA may indicate underlying cancer, which can predispose to thrombosis.", "protein": "carcinoembryonic antigen (CEA)", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression (PubMed:10864933, PubMed:10910050, PubMed:2803308). Mediates homophilic and heterophilic cel", "gene_name": "CEACAM5", "glycan_count": 12, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G05724UK", "G06110VR", "G14669DU", "G28681TP", "G39188ZX", "G41247ZX", "G53434XO", "G02815KT", "G31852PQ", "G71784JC", "G92275SC", "G82348BZ" ], "uniprot_id": "P06731" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "medium", "disease": "occult malignancy", "glycan_involvement": "Glycosylation modulates PSA detection and function.", "mechanism": "Elevated PSA may indicate prostate cancer, a risk factor for thrombosis.", "protein": "prostate-specific antigen (PSA)", "protein_enriched": { "function": "Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum", "gene_name": "KLK3", "glycan_count": 192, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00281HB", "G00553AN", "G00912UN", "G01650EU", "G02030ZB", "G03127AL", "G03382KH", "G03574QJ", "G03693IY", "G04576KS", "G06110VR", "G06356OH", "G06601SQ", "G08110WX", "G08146BT", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11629QQ", "G11870QZ", "G12511VU", "G12580WI", "G12708JQ", "G14176QY", "G14985NB", "G14994KB", "G15038BD", "G15169WU", "G15363AF", "G16204NU", "G16265MV", "G16828VN", "G17409FQ", "G17689DH", "G20732FY", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G23453IV", "G23505EP", "G23863VK", "G23869AA", "G24005JZ", "G24164CX", "G24835MQ", "G24954UD", "G25418HZ", "G25451PN", "G25987BV", "G26403SG", "G26915XM", "G28541PG", "G28975ZZ", "G29078QN", "G29239NH", "G29568VE", "G29880MM", "G29898ES", "G31618AH", "G31916IQ", "G33556XM", "G34306IB", "G34617SM", "G34730YF", "G35305EF", "G36923NX", "G37399XV", "G37412TK", "G37588ZB", "G37605QB", "G37868ZX", "G38946SH", "G40245CP", "G40834TG", "G42358LZ", "G42440OJ", "G44953PJ", "G45495MK", "G45504EY", "G45841FE", "G46422KL", "G46687AB", "G46754UW", "G46759WS", "G47518TP", "G47748JZ", "G47909JD", "G48414YA", "G49043NO", "G49278EO", "G49874UX", "G49991UY", "G50045TK", "G50903RY", "G51114UP", "G51413EV", "G51793MY", "G53604QR", "G54042WO", "G54059XR", "G54600FO", "G54612UD", "G54682XF", "G55220VL", "G55382TU", "G55783TD", "G55982TK", "G56749GV", "G56903ZB", "G57818FI", "G59354CW", "G59576IJ", "G59616TT", "G59626AS", "G59655SA", "G61138BO", "G61170KL", "G61726TP", "G61884GF", "G62067NB", "G62091GQ", "G62792OG", "G63276XU", "G63640QH", "G64394MX", "G65019XG", "G65059GX", "G65896IX", "G66538GV", "G66760KM", "G68698AP", "G70822IO", "G71681UC", "G72291OX", "G72667IM", "G72735IY", "G72791KH", "G72978AW", "G74120KH", "G74724QE", "G75798PH", "G75983OB", "G77252PU", "G77561JZ", "G78059CC", "G79568CQ", "G79939YZ", "G80333GO", "G80962OX", "G81198YO", "G81263BG", "G81295CK", "G81413UE", "G82348BZ", "G82463GQ", "G82514MH", "G82830MN", "G83555HU", "G83646BJ", "G83951ZY", "G84331QL", "G84362VL", "G84452RH", "G84467IZ", "G85144OK", "G85228QD", "G86182NS", "G86500WE", "G86752LQ", "G87139BK", "G87433AX", "G88374WZ", "G89738LW", "G89941FZ", "G90245IA", "G91337ZP", "G91473PK", "G92654OJ", "G93180LE", "G94854LT", "G95835XS", "G95865ZB", "G95977AE", "G96091TT", "G96095QD", "G98455QP", "G98472XA", "G98611JV", "G98666DD", "G99966GV" ], "uniprot_id": "P07288" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "medium", "disease": "pulmonary hypertension", "glycan_involvement": "Glycosylation affects BNP stability and clearance.", "mechanism": "BNP levels reflect right ventricular strain and pulmonary hypertension.", "protein": "brain natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12049185" }, { "confidence": "high", "disease": "MOG Antibody-Associated Disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG influences antigenicity and autoantibody binding.", "mechanism": "Autoantibodies target MOG, leading to demyelination and neuroinflammation.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12049199" }, { "confidence": "high", "disease": "Infectious mononucleosis", "glycan_involvement": "VCA is a glycoprotein; glycosylation is essential for antigenicity and immune recognition.", "mechanism": "VCA IgM is a reliable indicator of primary EBV infection, used for diagnosis.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049665" }, { "confidence": "high", "disease": "Infectious mononucleosis", "glycan_involvement": "EBNA is a glycoprotein; glycosylation affects immune detection.", "mechanism": "EBNA antibodies are used to confirm EBV infection and distinguish acute from past infection.", "protein": "Epstein-Barr nuclear antigen (EBNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049665" }, { "confidence": "medium", "disease": "Splenic rupture", "glycan_involvement": "Glycosylation of VCA may modulate immune response and tissue tropism.", "mechanism": "EBV infection leads to mononuclear cell infiltration and splenomegaly, predisposing to rupture.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "high", "disease": "Infectious mononucleosis", "glycan_involvement": "Heterophile antibodies recognize glycan epitopes on animal erythrocytes.", "mechanism": "Presence of heterophile antibodies is diagnostic for IM.", "protein": "Heterophile antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12049665" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Glycosylation may affect viral tropism for liver tissue.", "mechanism": "EBV infection can cause hepatitis as a complication.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "medium", "disease": "Tonsillar enlargement/airway obstruction", "glycan_involvement": "Glycosylation may influence immune cell interactions.", "mechanism": "EBV infection can cause lymphoid hyperplasia leading to airway obstruction.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "low", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation may affect protein aggregation.", "mechanism": "EBV is listed as a rare cause of ASR via amyloidosis.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may modulate autoantigenicity.", "mechanism": "EBV infection is associated with SLE and can trigger ASR.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "low", "disease": "Splenic vein thrombosis", "glycan_involvement": "Glycosylation may affect vascular interactions.", "mechanism": "EBV infection can be associated with splenic vein thrombosis, predisposing to rupture.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "medium", "disease": "Splenic rupture", "glycan_involvement": "Glycosylation may influence immune cell homing and tissue infiltration.", "mechanism": "EBV-induced splenomegaly and capsular thinning increase risk of rupture.", "protein": "Epstein-Barr virus viral capsid antigen (VCA)", "relationship_type": "causal", "source_pmcid": "PMC12049665" }, { "confidence": "high", "disease": "Premature Coronary Artery Disease (CAD)", "glycan_involvement": "Apolipoprotein(a) is heavily glycosylated, affecting its structure and function.", "mechanism": "Lp(a) promotes atherogenesis and thrombosis, accelerating CAD onset, especially in young adults.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal", "source_pmcid": "PMC12049667" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of apolipoprotein(a) modulates its interaction with vascular components.", "mechanism": "Lp(a) accumulates in arterial walls, promoting plaque formation.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal", "source_pmcid": "PMC12049667" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "O-glycosylation of apolipoprotein(a) influences its plasminogen-like activity.", "mechanism": "Apolipoprotein(a) mimics plasminogen, inhibiting fibrinolysis and increasing thrombosis risk.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal", "source_pmcid": "PMC12049667" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation affects apolipoprotein(a) size and function.", "mechanism": "Elevated Lp(a) increases risk of large-vessel ischemic stroke via prothrombotic and atherogenic effects.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal", "source_pmcid": "PMC12049667" }, { "confidence": "high", "disease": "Premature Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation status may affect Lp(a) plasma levels and detection.", "mechanism": "High Lp(a) identifies individuals at increased risk for early CAD.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049667" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation of kringle IV repeats modulates protein conformation.", "mechanism": "Apo(a) component of Lp(a) promotes lipid deposition and inflammation in arteries.", "protein": "Apolipoprotein(a)", "relationship_type": "causal", "source_pmcid": "PMC12049667" }, { "confidence": "medium", "disease": "Premature Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation may influence therapeutic efficacy and Lp(a) clearance.", "mechanism": "Novel therapies (PCSK9 inhibitors, antisense oligonucleotides) target Lp(a) to reduce CAD risk.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049667" }, { "confidence": "high", "disease": "Rheumatoid lung nodules", "glycan_involvement": "IgM is a heavily glycosylated immunoglobulin; glycosylation affects its immune complex formation and deposition.", "mechanism": "Rheumatoid factor interacts with macrophages to form necrobiotic nodules in lung tissue.", "protein": "Rheumatoid factor (IgM)", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "high", "disease": "Secondary spontaneous pneumothorax", "glycan_involvement": "Glycosylation of IgM influences its aggregation and pathogenicity.", "mechanism": "Rupture of rheumatoid nodules formed by immune complexes leads to pneumothorax.", "protein": "Rheumatoid factor (IgM)", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Rheumatoid lung nodules", "glycan_involvement": "Surface glycoproteins mediate immune cell interactions and nodule formation.", "mechanism": "Macrophages act as nidus for rheumatoid factor deposition, forming nodules.", "protein": "Macrophage surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Rheumatoid lung nodules", "glycan_involvement": "Methotrexate may alter glycoprotein expression on immune cells, affecting nodule formation.", "mechanism": "Methotrexate accelerates development/progression of necrobiotic nodules.", "protein": "Methotrexate-induced glycoprotein changes", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Rheumatoid lung nodules", "glycan_involvement": "Leflunomide may modulate glycoprotein-mediated immune responses.", "mechanism": "Leflunomide accelerates development/progression of necrobiotic nodules.", "protein": "Leflunomide-induced glycoprotein changes", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Secondary spontaneous pneumothorax", "glycan_involvement": "Drug effects on glycoprotein expression may increase nodule fragility.", "mechanism": "Methotrexate-induced nodules rupture, causing pneumothorax.", "protein": "Methotrexate-induced glycoprotein changes", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Secondary spontaneous pneumothorax", "glycan_involvement": "Drug effects on glycoprotein expression may increase nodule fragility.", "mechanism": "Leflunomide-induced nodules rupture, causing pneumothorax.", "protein": "Leflunomide-induced glycoprotein changes", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation state of IgM affects its detection and pathogenicity.", "mechanism": "Elevated rheumatoid factor is a diagnostic marker for rheumatoid arthritis.", "protein": "Rheumatoid factor (IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12049740" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycoproteins mediate immune cell recruitment and inflammation.", "mechanism": "Macrophage activation contributes to joint and lung pathology.", "protein": "Macrophage surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "low", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "Drug may affect hepatic glycoprotein processing.", "mechanism": "Methotrexate can cause hepatotoxicity, possibly via altered glycoprotein metabolism.", "protein": "Methotrexate-induced glycoprotein changes", "relationship_type": "causal", "source_pmcid": "PMC12049740" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation facilitates receptor binding and stability, enhancing tumor-promoting functions.", "mechanism": "Elevated SPP1 promotes cell proliferation, migration, invasion, immune evasion, and metastasis via integrin and CD44-mediated signaling.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12049823" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates SPP1's interaction with vascular cell receptors.", "mechanism": "SPP1 genetic variants (e.g., rs2728127) and upregulation linked to abnormal metabolic parameters and vascular injury.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "high", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylation affects immune cell receptor binding and immune modulation.", "mechanism": "SPP1 variants (e.g., rs11439060, rs1126616, rs9138) associated with increased risk and severity of SLE, rheumatoid arthritis, and MS.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "high", "disease": "Chronic inflammatory conditions", "glycan_involvement": "Glycosylation required for secretion and extracellular matrix interactions.", "mechanism": "Elevated SPP1 drives inflammation and tissue remodeling; variants and epigenetic changes increase susceptibility.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation enhances receptor binding and metastatic potential.", "mechanism": "SPP1 upregulation (via variants and TFs) promotes metastasis, immune evasion, and profibrogenic signaling in HCC.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12049823" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation supports ECM interactions and metastatic spread.", "mechanism": "RUNX2-driven SPP1 overexpression increases cell adhesion and lung metastasis.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12049823" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation stabilizes SPP1 and enhances cell signaling.", "mechanism": "GLI1-mediated SPP1 upregulation promotes tumor sphere formation and aggressiveness.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "causal", "source_pmcid": "PMC12049823" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation required for SPP1 secretion and ECM remodeling.", "mechanism": "High glucose induces activating histone marks, increasing SPP1 and promoting kidney damage.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune cell interactions.", "mechanism": "SPP1 variants (rs1126616, rs9138) and upregulation linked to increased disease risk and severity.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation facilitates vascular cell adhesion and inflammation.", "mechanism": "SPP1 variant rs1126616 associated with increased risk and burden of atherosclerosis.", "protein": "Secreted phosphoprotein 1 (SPP1) / Osteopontin (OPN)", "protein_enriched": { "function": "Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction", "gene_name": "SPP1", "glycan_count": 12, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G40740AD", "G58001LT", "G88713AC", "G27391WQ", "G29068FM", "G43417UB", "G57321FI", "G71838YU", "G23863VK", "G48414YA", "G78059CC", "G84467IZ" ], "uniprot_id": "P10451" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049823" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "PRF1 is glycosylated, which is important for its stability and function.", "mechanism": "Mutations in PRF1 lead to defective cytolytic function, causing immune dysregulation and HLH.", "protein": "Perforin-1 (PRF1)", "protein_enriched": { "function": "Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, Pub", "gene_name": "PRF1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G09831WQ", "G31309XD", "G45395BF", "G83460ZZ" ], "uniprot_id": "P14222" }, "relationship_type": "causal", "source_pmcid": "PMC12049859" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "sIL2Ra is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "Elevated sIL2Ra reflects T-cell activation and is a diagnostic marker for HLH.", "protein": "Soluble Interleukin-2 Receptor alpha (sIL2Ra/CD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12049859" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is glycosylated, which may affect its serum stability.", "mechanism": "Hyperferritinemia is a hallmark of HLH due to macrophage activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation status may influence PRF1 function and disease presentation.", "mechanism": "Defective PRF1 can mimic DIC-like laboratory findings due to immune dysregulation.", "protein": "Perforin-1 (PRF1)", "protein_enriched": { "function": "Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, Pub", "gene_name": "PRF1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G09831WQ", "G31309XD", "G45395BF", "G83460ZZ" ], "uniprot_id": "P14222" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation affects sIL2Ra detection in serum.", "mechanism": "Elevated sIL2Ra can help distinguish HLH from DIC.", "protein": "Soluble Interleukin-2 Receptor alpha (sIL2Ra/CD25)", "relationship_type": "differential diagnosis", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Q fever (Coxiella burnetii infection)", "glycan_involvement": "Glycosylation may modulate PRF1 immune response to infection.", "mechanism": "Coxiella infection can trigger HLH in individuals with PRF1 dysfunction.", "protein": "Perforin-1 (PRF1)", "protein_enriched": { "function": "Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, Pub", "gene_name": "PRF1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G09831WQ", "G31309XD", "G45395BF", "G83460ZZ" ], "uniprot_id": "P14222" }, "relationship_type": "causal (trigger for HLH)", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Q fever (Coxiella burnetii infection)", "glycan_involvement": "Glycosylation impacts sIL2Ra levels in serum.", "mechanism": "Elevated sIL2Ra indicates immune activation in HLH triggered by Q fever.", "protein": "Soluble Interleukin-2 Receptor alpha (sIL2Ra/CD25)", "relationship_type": "biomarker (HLH secondary to infection)", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Q fever (Coxiella burnetii infection)", "glycan_involvement": "Glycosylation may affect ferritin stability and detection.", "mechanism": "Elevated ferritin is seen in HLH secondary to Coxiella infection.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker (HLH secondary to infection)", "source_pmcid": "PMC12049859" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation of target proteins may affect drug efficacy.", "mechanism": "Etoposide inhibits DNA synthesis in activated immune cells, reducing cytokine storm in HLH.", "protein": "Etoposide target proteins (general)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12049859" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation is essential for sIL2Ra function and detection.", "mechanism": "sIL2Ra is part of HLH-2004 diagnostic criteria.", "protein": "Soluble Interleukin-2 Receptor alpha (sIL2Ra/CD25)", "relationship_type": "diagnostic criterion", "source_pmcid": "PMC12049859" }, { "confidence": "high", "disease": "Budd\u2013Chiari syndrome", "glycan_involvement": "Glycosylation required for secretion and activity; deficiency may relate to glycosylation defects.", "mechanism": "Protein C deficiency leads to increased risk of hepatic vein thrombosis.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC12050134" }, { "confidence": "medium", "disease": "Budd\u2013Chiari syndrome", "glycan_involvement": "Glycosylation affects stability and plasma half-life.", "mechanism": "Protein S deficiency impairs anticoagulant pathways, predisposing to thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12050134" }, { "confidence": "medium", "disease": "Budd\u2013Chiari syndrome", "glycan_involvement": "N-glycosylation modulates anticoagulant activity.", "mechanism": "Antithrombin deficiency reduces inhibition of coagulation, increasing thrombosis risk.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC12050134" }, { "confidence": "high", "disease": "Budd\u2013Chiari syndrome", "glycan_involvement": "Glycosylation influences secretion and function.", "mechanism": "Factor V Leiden mutation increases thrombosis risk in hepatic veins.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12050134" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns in cancer.", "mechanism": "Elevated alpha-fetoprotein is used for surveillance of liver cancer in BCS patients.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12050134" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin links to glycoproteins (dystroglycan, sarcoglycans) in the DGC.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex, leading to membrane instability and muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12055071" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystroglycan is heavily glycosylated; glycosylation is essential for ECM binding.", "mechanism": "Disruption of dystroglycan function due to absence of dystrophin impairs membrane integrity.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Sarcoglycans are glycoproteins; glycosylation affects complex stability.", "mechanism": "Loss of dystrophin destabilizes sarcoglycan complex, contributing to membrane fragility.", "protein": "Sarcoglycans", "relationship_type": "causal", "source_pmcid": "PMC12055071" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Via DGC disruption involving glycoproteins.", "mechanism": "Dystrophin deficiency leads to cardiac muscle membrane instability and progressive cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of dystroglycan is critical for cardiac ECM interactions.", "mechanism": "Impaired dystroglycan function in heart muscle contributes to cardiac complications in DMD.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12055071" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restores DGC and glycoprotein interactions.", "mechanism": "Restoration of dystrophin expression (gene therapy, HDAC inhibition) improves muscle function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation status modulates function.", "mechanism": "Targeting dystroglycan glycosylation may improve membrane stability.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct glycosylation, but involved in pathway affecting glycoprotein function.", "mechanism": "HDAC inhibition (givinostat) promotes PGC-1\u03b1 activity, supporting mitochondrial biogenesis.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation changes may serve as biomarkers.", "mechanism": "Altered sarcoglycan levels reflect DGC disruption and disease severity.", "protein": "Sarcoglycans", "relationship_type": "biomarker", "source_pmcid": "PMC12055071" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Defective glycosylation impairs function.", "mechanism": "Glycosylation status of dystroglycan correlates with disease progression.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "biomarker", "source_pmcid": "PMC12055071" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation modulates complement activation and stability.", "mechanism": "Upregulated in diabetes; associated with inflammation and insulin resistance.", "protein": "Complement C1s", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F1P6S5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation affects complement assembly and function.", "mechanism": "Upregulated in early diabetic kidney disease; promotes complement-mediated renal injury.", "protein": "Complement C7", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0N6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation influences fibrinogen's clotting properties.", "mechanism": "Elevated in diabetes; contributes to hypercoagulability and atherosclerosis.", "protein": "Fibrinogen alpha chain", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0G5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates fibrin polymerization.", "mechanism": "Upregulated in diabetes; increases risk of thrombosis.", "protein": "Fibrinogen gamma chain", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0G7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "Vascular dysfunction", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Elevated in diabetes; promotes procoagulant state and vascular complications.", "protein": "Coagulation factor VII", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0H0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation critical for receptor function and ligand binding.", "mechanism": "Upregulated in diabetes; marker of immune dysregulation and inflammation.", "protein": "Interleukin-2 receptor subunit beta", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0H2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation essential for ER function and glycoprotein processing.", "mechanism": "Downregulated in diabetes; involved in glycoprotein metabolism and insulin signaling.", "protein": "Protein kinase C substrate 80K-H (PRKCSH)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0H3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation may affect stability and localization.", "mechanism": "Downregulated in diabetes; protective via NRF2 regulation in kidney disease.", "protein": "E3 ubiquitin-protein ligase Mdm2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0H4" }, "relationship_type": "protective", "source_pmcid": "PMC12057883" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Upregulated in diabetes; links coagulation and inflammation.", "protein": "Coagulation factor XII", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0H1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12057883" }, { "confidence": "medium", "disease": "Cardiac complications", "glycan_involvement": "Indirect; PKC signaling modulates glycoprotein trafficking.", "mechanism": "Upregulated in diabetes; promotes insulin resistance, vascular dysfunction, and cardiac issues.", "protein": "Protein kinase C alpha", "relationship_type": "causal", "source_pmcid": "PMC12057883" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Impaired N-glycosylation due to GDP-mannose deficiency.", "mechanism": "PMM2 mutations cause defective GDP-mannose synthesis, leading to global hypoglycosylation of proteins.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Defective N-glycosylation alters transferrin isoform profile.", "mechanism": "Altered transferrin glycoforms are used in laboratory diagnosis of PMM2-CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "Cerebellar atrophy", "glycan_involvement": "Defective N-glycosylation in neuronal proteins.", "mechanism": "Hypoglycosylation of neuronal glycoproteins impairs their localization and function, contributing to neurodegeneration.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "Immunological dysfunction", "glycan_involvement": "Defective N- and O-glycosylation in PBMCs.", "mechanism": "Hypoglycosylation of immune cell surface glycoproteins impairs immune function.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "Coagulation abnormalities", "glycan_involvement": "Defective N-glycosylation of plasma proteins.", "mechanism": "Hypoglycosylation of coagulation factors leads to abnormal hemostasis.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "low", "disease": "Retinopathy", "glycan_involvement": "Defective N-glycosylation in retinal proteins.", "mechanism": "Hypoglycosylation affects retinal glycoproteins, contributing to visual defects.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Altered O-glycosylation/glycosaminoglycan attachment.", "mechanism": "Increased UDP-glucuronic acid enhances glycosaminoglycan biosynthesis, potentially altering extracellular matrix composition.", "protein": "Glycosaminoglycan core proteins", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Unimpaired O-glycosylation in PBMCs.", "mechanism": "UDP-GalNAc and UDP-GlcNAc levels remain normal, suggesting mucin-type O-glycosylation is preserved.", "protein": "Mucin-type glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12059080" }, { "confidence": "high", "disease": "Glycogenosis (hepatic)", "glycan_involvement": "Altered glycosylation substrate flux affects glycogen homeostasis.", "mechanism": "Increased UDP-glucose leads to excessive glycogen synthesis in hepatocytes.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12059080" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Targeting glycosylation pathway intermediates.", "mechanism": "Restoring GDP-mannose or supplementing glutamine may improve glycosylation and cell metabolism.", "protein": "Glycoproteins (multiple, unspecified)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12059080" }, { "confidence": "high", "disease": "Corneal Opacity", "glycan_involvement": "O-glycosylation of mucins is directly affected.", "mechanism": "Disruption of mucin-type O-glycan biosynthesis impairs mucin layer, leading to epithelial damage and opacity.", "protein": "GALNT9", "protein_enriched": { "function": "", "gene_name": "RNF148", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N7C7" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "high", "disease": "Corneal Opacity", "glycan_involvement": "Indirect; signaling pathways may regulate glycoprotein expression.", "mechanism": "Loss impairs cGMP-PKG and oxytocin signaling, affecting collagen synthesis and epithelial integrity.", "protein": "RGS2", "protein_enriched": { "function": "Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound ", "gene_name": "RGS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41220" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Dry Eye Disease", "glycan_involvement": "Indirect; affects tear film glycoprotein composition.", "mechanism": "Involvement in oxytocin signaling pathway linked to dry eye pathogenesis.", "protein": "RGS2", "protein_enriched": { "function": "Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound ", "gene_name": "RGS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41220" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12060066" }, { "confidence": "high", "disease": "Corneal Dystrophy", "glycan_involvement": "Direct O-glycosylation of mucins.", "mechanism": "Essential for mucin-type O-glycan biosynthesis; disruption leads to dystrophy.", "protein": "GALNT9", "protein_enriched": { "function": "", "gene_name": "RNF148", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N7C7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Keratoconus", "glycan_involvement": "Structural glycoprotein; glycosylation may affect filament stability.", "mechanism": "Previously associated with keratoconus; structural role in corneal epithelium.", "protein": "KRT80", "protein_enriched": { "function": "May play a role in late hair differentiation", "gene_name": "KRT40", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6A162" }, "relationship_type": "biomarker", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Keratoconus", "glycan_involvement": "Possible O-glycosylation affecting barrier properties.", "mechanism": "Previously linked to keratoconus; involved in epithelial barrier function.", "protein": "SPRR1A", "protein_enriched": { "function": "Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All t", "gene_name": "SPRR2B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35325" }, "relationship_type": "biomarker", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Corneal Opacity", "glycan_involvement": "Indirect; impacts mucin glycoprotein production.", "mechanism": "Interacts with TP53 in cellular senescence pathway, affecting mucin expression and epithelial turnover.", "protein": "TRIM39", "protein_enriched": { "function": "E3 ubiquitin-protein ligase (PubMed:22529100). May facilitate apoptosis by inhibiting APC/C-Cdh1-mediated poly-ubiquitination and subsequent proteasome-mediated degradation of the pro-apoptotic protei", "gene_name": "TRIM39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HCM9" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Corneal Opacity", "glycan_involvement": "Indirect; may affect glycoprotein synthesis via mitochondrial function.", "mechanism": "Disruption of mitochondrial ribosomal assembly in limbal progenitor cells affects corneal maintenance.", "protein": "GTPBP10", "protein_enriched": { "function": "Involved in the biogenesis of the 60S ribosomal subunit (PubMed:32669547). Acts as a TP53 repressor, preventing TP53 stabilization and cell cycle arrest (PubMed:20308539)", "gene_name": "GTPBP4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BZE4" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Corneal Opacity", "glycan_involvement": "Possible glycosylation of adhesion molecules.", "mechanism": "Impaired cell\u2013cell adhesion in corneal progenitor cells disrupts corneal architecture.", "protein": "TENM4", "protein_enriched": { "function": "Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Reg", "gene_name": "TENM4", "glycan_count": 11, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G02886BB", "G49108TO", "G31852PQ", "G62765YT", "G80920RR", "G02815KT", "G27947YN", "G41247ZX", "G98611JV", "G43417UB", "G00912UN" ], "uniprot_id": "Q6N022" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "medium", "disease": "Corneal Morphology Abnormality", "glycan_involvement": "Indirect; may affect glycoprotein expression in immune cells.", "mechanism": "Immune modulation in corneal T/NK cells may contribute to abnormal morphology.", "protein": "IK", "protein_enriched": { "function": "Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-", "gene_name": "IKZF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q13422" }, "relationship_type": "causal", "source_pmcid": "PMC12060066" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Increased sialylated Lewis a (sLe a) N-glycan on serum glycoproteins", "mechanism": "Elevated serum CA19-9 (sialyl Lewis a) is a diagnostic marker for pancreatic cancer.", "protein": "Lewis a antigen (CA19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "Gastrointestinal cancer", "glycan_involvement": "Increased sialylated Lewis a (sLe a) N-glycan", "mechanism": "CA19-9 is elevated in various GI cancers, reflecting altered glycosylation.", "protein": "Lewis a antigen (CA19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "Cancer (general, including HCC)", "glycan_involvement": "Increased sialylated Lewis x N-glycan on serum glycoproteins", "mechanism": "Elevated sLe x is associated with cancer progression and prognosis.", "protein": "Sialyl Lewis x antigen (sLe x)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Increased N-acetylglucosamine and sialic acid on acute-phase proteins", "mechanism": "GlycA/B NMR signals reflect N-acetyl methyl groups of glycoproteins, elevated in inflammation.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "General inflammation", "glycan_involvement": "Altered N-glycosylation (increased N-acetyl methyl groups)", "mechanism": "GlycA/B NMR signals are elevated in various inflammatory diseases.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Changes in N-acetyl methyl group content", "mechanism": "Altered GlycA/B profiles observed in Parkinson\u2019s disease.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Changes in N-acetyl methyl group content", "mechanism": "Altered GlycA/B profiles observed in Alzheimer\u2019s disease.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Increased N-acetyl methyl groups on glycoproteins", "mechanism": "GlycA/B NMR signals elevated in IBD.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Changes in N-glycan branching and sialylation", "mechanism": "Altered glycosylation profiles in MASLD and progression to HCC.", "protein": "Acute-phase glycoproteins (GlycA/B)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Increased core fucosylation, elevated (s)Le x/a, increased \u03b12,6-sialylation, altered glycan branching", "mechanism": "Distinct glycosylation profiles (increased core fucosylation, (s)Le x/a, altered sialylation) discriminate HCC from controls.", "protein": "Acute-phase glycoproteins (multiple, e.g., AAT, TF, HP, CFH)", "relationship_type": "biomarker", "source_pmcid": "PMC12060095" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Overexpression (induced by lncRNA ODRUL) leads to doxorubicin efflux and resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation supports membrane localization.", "mechanism": "MALAT1 lncRNA upregulates P-gp, promoting cisplatin resistance via increased drug efflux.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation stabilizes transporter.", "mechanism": "ANRIL lncRNA induces P-gp expression, causing cisplatin and 5-FU resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation critical for function.", "mechanism": "Overexpression leads to efflux of multiple chemotherapeutics, causing multidrug resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation required for surface expression.", "mechanism": "High P-gp expression correlates with poor prognosis and chemoresistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12061905" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation supports transporter activity.", "mechanism": "KCNQ1OT1 lncRNA upregulates P-gp, MRP5, and LRP1, causing oxaliplatin resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "HOTTIP lncRNA upregulates P-gp, leading to gemcitabine resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "N-glycosylation supports function.", "mechanism": "High P-gp expression in immune cells leads to chemoresistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation required for transporter activity.", "mechanism": "linc-VLDLR lncRNA upregulates ABCG2, promoting multidrug resistance.", "protein": "ABCG2 (BCRP)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "medium", "disease": "Platinum-resistant ovarian cancer", "glycan_involvement": "N-glycosylation supports function.", "mechanism": "HOTAIR lncRNA upregulates P-gp and repairs DNA, causing platinum resistance.", "protein": "P-glycoprotein-1 (ABCB1/MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12061905" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Env glycosylation modulates immune evasion and cell tropism.", "mechanism": "Mediates viral entry into host cells via glycan-dependent receptor binding.", "protein": "HIV-1 Env", "relationship_type": "causal", "source_pmcid": "PMC12065270" }, { "confidence": "high", "disease": "Gene therapy inefficiency", "glycan_involvement": "Glycosylation affects VSV-G stability and infectivity.", "mechanism": "Used to pseudotype lentiviral vectors, enhancing stability and broadening tropism.", "protein": "VSV-G", "protein_enriched": { "function": "Attaches the virus to host LDL receptors, inducing clathrin-dependent endocytosis of the virion (PubMed:20941355, PubMed:23589850). In the endosome, the acidic pH induces conformational changes in the", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03522" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12065270" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect HIF-1\u03b1 stability and function (not detailed in article).", "mechanism": "HIF-1\u03b1 promotes survival and metabolic adaptation in hypoxic tumors; inhibitors like PX-478 are in clinical trials.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12065270" }, { "confidence": "high", "disease": "CAR-T cell therapy resistance", "glycan_involvement": "Indirect; HIF-1\u03b1 may regulate glycoprotein expression affecting viral entry.", "mechanism": "Hypoxia-induced HIF-1\u03b1 activation impairs lentiviral entry, reducing CAR-T cell transduction efficiency.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "protective", "source_pmcid": "PMC12065270" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "GLUT1 is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Upregulated by HIF-1\u03b1 under hypoxia, supporting metabolic adaptation in tumors.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12065270" }, { "confidence": "high", "disease": "Gene therapy inefficiency", "glycan_involvement": "Indirect; may regulate glycoproteins involved in viral entry.", "mechanism": "HIF-1\u03b1 activation under hypoxia impairs lentiviral entry and genome integration.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12065270" }, { "confidence": "medium", "disease": "CAR-T cell therapy resistance", "glycan_involvement": "Glycosylation modulates VSV-G-mediated membrane fusion.", "mechanism": "VSV-G pseudotyping improves lentiviral transduction of resistant immune cells.", "protein": "VSV-G", "protein_enriched": { "function": "Attaches the virus to host LDL receptors, inducing clathrin-dependent endocytosis of the virion (PubMed:20941355, PubMed:23589850). In the endosome, the acidic pH induces conformational changes in the", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03522" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12065270" }, { "confidence": "medium", "disease": "Gene therapy inefficiency", "glycan_involvement": "GLUT1 glycosylation is required for proper function.", "mechanism": "GLUT1 upregulation by HIF-1\u03b1 may contribute to metabolic changes that impair viral entry.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12065270" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Indirect; may regulate host glycoproteins involved in viral entry.", "mechanism": "HIF-1\u03b1 activation under hypoxia reduces HIV-1 lentiviral entry into host cells.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "protective", "source_pmcid": "PMC12065270" }, { "confidence": "high", "disease": "Gene therapy inefficiency", "glycan_involvement": "Env glycosylation affects vector safety and tropism.", "mechanism": "Replacement of HIV-1 Env with VSV-G improves lentiviral vector performance for gene therapy.", "protein": "HIV-1 Env", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12065270" }, { "confidence": "medium", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Altered sialylation and fucosylation of O-linked glycans on MUC1 during tumorigenesis.", "mechanism": "MUC1 is a major transmembrane mucin altered in SGTs, with changes in glycosylation during malignant transformation.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Increased sialylation and fucosylation of O-linked glycans.", "mechanism": "MUC5B is a secreted mucin with glycosylation changes in SGTs, contributing to altered cell surface properties.", "protein": "MUC5B", "protein_enriched": { "function": "Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus", "gene_name": "MUC5B", "glycan_count": 47, "glycosylation_sites_count": 38, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G62765YT", "G80920RR", "G84452RH", "G48414YA", "G66760KM", "G57321FI", "G64527OM", "G39188ZX", "G31852PQ", "G70822IO", "G75983OB", "G05724UK", "G06110VR", "G10773YW", "G29880MM", "G46687AB", "G82119TF", "G02030ZB", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G40142JY", "G42665KV", "G49582PC", "G58272ZE", "G63110FE", "G63628AV", "G63760GT", "G64973KT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G78315FS", "G79243QP", "G81006GJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q9HC84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Altered O-glycosylation, especially sialylation and fucosylation.", "mechanism": "MUC7 is a secreted mucin with glycosylation changes observed in SGTs.", "protein": "MUC7", "protein_enriched": { "function": "Potential calcium-dependent cell-adhesion protein", "gene_name": "PCDH9", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G41071NU", "G48414YA", "G00912UN", "G37995HC", "G44753VC", "G49906RN", "G58087IP", "G76295SF", "G85554PZ", "G13694XX", "G84225JN", "G62765YT", "G61256FT", "G07755XJ", "G06356OH", "G47518TP", "G82830MN", "G84452RH", "G80920RR", "G22310AV", "G38663NM", "G43089EG" ], "uniprot_id": "Q9HC56" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "high", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Increased sialylation and aberrant fucosylation patterns.", "mechanism": "Global changes in glycosylation (sialylation, fucosylation) of mucin-type glycoproteins are associated with SGTs.", "protein": "General mucin-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Malignant SGTs (e.g., MEC, ADCC, Ca-ex-PA)", "glycan_involvement": "Elevated sialylation and fucosylation facilitate malignant phenotype.", "mechanism": "Aberrant glycosylation (especially sialylation/fucosylation) promotes tumor progression, immune evasion, and metastasis.", "protein": "General mucin-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Carcinoma ex pleomorphic adenoma (Ca-ex-PA)", "glycan_involvement": "Altered sialylation/fucosylation detectable by ATR-FTIR.", "mechanism": "Glycosylation changes in mucin-type glycoproteins may indicate malignant transformation of PA.", "protein": "General mucin-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Benign SGTs (e.g., PA, Warthin tumor)", "glycan_involvement": "Intermediate or less aberrant sialylation/fucosylation compared to malignant SGTs.", "mechanism": "Benign SGTs show glycosylation profiles distinct from malignant SGTs and normal tissue.", "protein": "General mucin-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "high", "disease": "Normal salivary gland tissue", "glycan_involvement": "Balanced sialylation and fucosylation.", "mechanism": "Normal glycosylation patterns maintain tissue homeostasis and prevent tumorigenesis.", "protein": "General mucin-associated glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12071147" }, { "confidence": "medium", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Targeting sialylation/fucosylation with neuraminidase/fucosidase.", "mechanism": "Enzymatic removal of sialic acid and fucose residues alters tumor-specific glycoprotein signatures, suggesting potential for targeted therapy or diagnostics.", "protein": "General mucin-associated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12071147" }, { "confidence": "high", "disease": "Salivary gland tumors (SGTs)", "glycan_involvement": "Glycan fingerprint region (850\u20131250 cm\u22121) reflects glycosylation changes.", "mechanism": "ATR-FTIR detects glycosylation-dependent spectral differences, enabling discrimination of tumor vs. normal tissue.", "protein": "General mucin-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12071147" }, { "confidence": "high", "disease": "Cervical carcinoma", "glycan_involvement": "Increased FA2 (G0F), A2G2, and A2G2S1; decreased FA2G2 (G2F); altered sialylation and fucosylation.", "mechanism": "Elevated agalactosylated (FA2/G0F) and mono-sialylated N-glycans in serum indicate malignant transformation.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Decreased FA2B (bisected), increased A4G4S4 (tetra-sialylated), elevated A2G2 and A2G2S1.", "mechanism": "Distinct decrease in bisected N-glycans and increase in highly branched tetra-sialylated glycans reflect chronic inflammation and tissue remodeling.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "medium", "disease": "Myoma uteri (uterine fibroids)", "glycan_involvement": "Increased A2G2 and A2G2S1; decreased FA2G2S1.", "mechanism": "Elevated bi-antennary N-glycans (A2G2, A2G2S1) in serum distinguish myoma from healthy controls.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "high", "disease": "Cervical carcinoma", "glycan_involvement": "Increased FA2 (G0F) in serum.", "mechanism": "Elevated agalactosylated N-glycans (FA2/G0F) are associated with cancer-related immune evasion and inflammation.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Lower FA2B levels in serum.", "mechanism": "Decreased bisected N-glycans (FA2B) reflect altered glycosyltransferase activity in endometriosis.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "high", "disease": "Cervical carcinoma", "glycan_involvement": "A2G2 and A2G2S1 increased by ~40% in cancer vs. control.", "mechanism": "Elevated A2G2 and A2G2S1 serve as robust serum markers for cervical cancer.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "A4G4S4 elevated in endometriosis.", "mechanism": "Increased tetra-antennary, tetra-sialylated glycans (A4G4S4) are unique to endometriosis.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "medium", "disease": "Cervical carcinoma", "glycan_involvement": "Lower FA2G2 (G2F) in cancer.", "mechanism": "Decreased core fucosylation (lower FA2G2) is associated with cervical cancer progression.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "medium", "disease": "Myoma uteri (uterine fibroids)", "glycan_involvement": "Lower FA2G2S1 in myoma.", "mechanism": "Decreased FA2G2S1 (fucosylated, mono-sialylated glycan) helps distinguish myoma from other conditions.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "medium", "disease": "Cervical carcinoma", "glycan_involvement": "Increased mono-sialylated, decreased fucosylated glycans.", "mechanism": "Altered sialylation and fucosylation patterns in serum N-glycans are linked to tumor progression and immune modulation.", "protein": "Serum glycoproteins (aggregate)", "relationship_type": "biomarker", "source_pmcid": "PMC12071406" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "MOG is a heavily glycosylated myelin protein; glycosylation affects its immunogenicity and stability.", "mechanism": "Elevated MOG in brain and exosomes reflects myelin/oligodendrocyte injury in AD-type neurodegeneration.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "PLP is glycosylated; glycosylation is essential for myelin membrane structure.", "mechanism": "Increased PLP in brain and serum exosomes indicates oligodendrocyte de-differentiation and white matter injury in AD.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation modulates axon-glia interactions.", "mechanism": "Elevated MAG in brain and exosomes reflects mature oligodendrocyte/myelin degeneration in AD.", "protein": "Myelin-Associated Glycoprotein (MAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "PDGFRA is N-glycosylated; glycosylation regulates receptor trafficking and signaling.", "mechanism": "Increased PDGFRA in exosomes marks non-myelinating glial activation and white matter pathology in AD.", "protein": "Platelet-Derived Growth Factor Receptor Alpha (PDGFRA)", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemota", "gene_name": "PDGFRA", "glycan_count": 4, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G28541PG", "G80920RR", "G00912UN", "G49108TO" ], "uniprot_id": "P16234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GALC is glycosylated; glycosylation affects enzyme stability and function.", "mechanism": "Elevated GALC in exosomes reflects glial response to white matter degeneration in AD.", "protein": "Galactocerebrosidase (GALC)", "protein_enriched": { "function": "Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine (PubMed:8281145, PubMed:8399327). Enzyme with very low activity responsible for the lysosomal c", "gene_name": "GALC", "glycan_count": 5, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G47950XN", "G31852PQ", "G39446WN", "G41247ZX", "G49108TO" ], "uniprot_id": "P54803" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation influences A\u03b2 production and aggregation.", "mechanism": "Increased A\u03b2PP in serum exosomes is associated with AD-type neurodegeneration.", "protein": "Amyloid Precursor Protein (APP/A\u03b2PP)", "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation and toxicity.", "mechanism": "Elevated Tau in brain and exosomes reflects neurodegeneration and is a core AD biomarker.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation of Tau influences phosphorylation and aggregation.", "mechanism": "Increased pTau in brain and exosomes is a hallmark of AD neurodegeneration.", "protein": "Phosphorylated Tau (pTau)", "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Ubiquitin can be glycosylated; glycosylation may affect proteasomal targeting.", "mechanism": "Elevated ubiquitin in brain and exosomes reflects increased protein degradation and neurodegeneration in AD.", "protein": "Ubiquitin", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P62988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation affects filament assembly and astrocyte function.", "mechanism": "Increased GFAP in exosomes indicates astrocyte activation and gliosis in AD.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071450" }, { "confidence": "high", "disease": "PGM1-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Mixed N- and O-glycosylation defects in ER and Golgi.", "mechanism": "PGM1 deficiency depletes UDP-glucose/UDP-galactose, impairing glycosylation.", "protein": "PGM1", "relationship_type": "causal", "source_pmcid": "PMC12071635" }, { "confidence": "high", "disease": "PGM1-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Altered N-glycosylation profile (CDT test).", "mechanism": "Carbohydrate-deficient transferrin detected in serum reflects abnormal glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "high", "disease": "Leigh syndrome", "glycan_involvement": "Indirect; energy deficit impacts glycosylation.", "mechanism": "Pathogenic variants in NDUFA13 impair complex I activity, causing neurodegeneration.", "protein": "NDUFA13", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "NDUFA12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UI09" }, "relationship_type": "causal", "source_pmcid": "PMC12071635" }, { "confidence": "high", "disease": "PGM1-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "UDP-hexoses are essential sugar donors for glycan synthesis.", "mechanism": "Profound depletion of UDP-hexoses in patient fibroblasts.", "protein": "UDP-hexose", "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "medium", "disease": "PGM1-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Glycosylation of ceramides affected.", "mechanism": "Increased levels in PGM1-CDG fibroblasts indicate altered glycosphingolipid metabolism.", "protein": "Ceramide/Hexosylceramide/Lactosylceramide", "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "medium", "disease": "Leigh syndrome", "glycan_involvement": "Indirect; PI involved in membrane glycoprotein anchoring.", "mechanism": "Decreased PI in Leigh syndrome and CI-deficient fibroblasts.", "protein": "Phosphatidylinositol", "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "medium", "disease": "Leigh syndrome", "glycan_involvement": "Indirect; LPC influences membrane glycoprotein environment.", "mechanism": "Decreased LPC in Leigh syndrome and CI-deficient fibroblasts.", "protein": "Lysophosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "medium", "disease": "Complex I deficiency", "glycan_involvement": "Sphingomyelin is a glycosylated lipid abundant in neurons.", "mechanism": "Decreased sphingomyelin in CI-deficient cells, not in NDUFA13 cells.", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12071635" }, { "confidence": "low", "disease": "Leigh syndrome", "glycan_involvement": "Reduced glycosylation may affect energy metabolism.", "mechanism": "PGM1 deficiency may partially attenuate mitochondrial dysfunction by redirecting glucose flux.", "protein": "PGM1", "relationship_type": "protective", "source_pmcid": "PMC12071635" }, { "confidence": "high", "disease": "PGM1-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Restores glycan synthesis in ER and Golgi.", "mechanism": "Oral D-galactose supplementation increases UDP-hexose pools and improves glycosylation.", "protein": "PGM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12071635" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation may affect BTN1A1's immunomodulatory function and cell surface expression.", "mechanism": "Immunomodulation via inhibition of T-cell proliferation and reduction of IL-2/IFN\u03b3; possible involvement in xanthine oxidase pathway.", "protein": "BTN1A1", "relationship_type": "protective/causal", "source_pmcid": "PMC12074030" }, { "confidence": "high", "disease": "Early-onset COPD", "glycan_involvement": "Glycosylation may modulate BTN1A1's interaction with immune cells.", "mechanism": "Reduces risk of early COPD, likely through immune regulation and inflammation suppression.", "protein": "BTN1A1", "relationship_type": "protective/causal", "source_pmcid": "PMC12074030" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation influences receptor function and cell signaling.", "mechanism": "Promotes vascular remodeling and angiogenesis, contributing to airway narrowing and inflammation.", "protein": "TIE-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation affects cell surface expression and immune recognition.", "mechanism": "Activates NK cells in response to stress/infection, promoting COPD progression.", "protein": "MICB_MICA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Elevated G-CSF increases neutrophil recruitment and inflammation, associated with acute exacerbations.", "protein": "G-CSF", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Potential glycosylation may affect protein stability and function.", "mechanism": "Cytoskeletal remodeling; hypomethylation linked to respiratory disease protection.", "protein": "Septin-8", "protein_enriched": { "function": "Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in the cytoarchitecture of neurons, including dendritic arborization and dendritic spines, and in GABA", "gene_name": "SEPTIN11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NVA2" }, "relationship_type": "protective", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation essential for cortisol binding and transport.", "mechanism": "Transports cortisol to inflammation sites, suppressing immune response and organ damage.", "protein": "CBG", "relationship_type": "protective", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation critical for laminin binding and cell-matrix interactions.", "mechanism": "Stabilizes muscle and cell signaling; downregulation by oxidative stress may protect against hypertension and COPD.", "protein": "DAG1", "relationship_type": "protective", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "Early-onset COPD", "glycan_involvement": "Glycosylation may affect regulatory function.", "mechanism": "Reduces risk of early COPD, possibly via regulation of inflammation.", "protein": "TNFAIP8", "relationship_type": "protective", "source_pmcid": "PMC12074030" }, { "confidence": "medium", "disease": "Later-onset COPD", "glycan_involvement": "N-glycosylation required for stability and anti-protease activity.", "mechanism": "Inhibits proteases, reducing tissue damage and inflammation.", "protein": "Alpha-1-antitrypsin", "relationship_type": "protective", "source_pmcid": "PMC12074030" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation required for proper membrane localization and function.", "mechanism": "Reduced expression in dystrophin-deficient muscle; associated with membrane instability.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12077386" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation essential for sarcoglycan complex stability.", "mechanism": "Reduced expression in dystrophin-deficient muscle; contributes to membrane fragility.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may affect membrane association.", "mechanism": "Upregulated in dystrophin-deficient muscle; compensates for dystrophin loss.", "protein": "utrophin", "protein_enriched": { "function": "Transcriptional regulator implicated in neuronal determination. Mediates calcium-dependent transcription activation by binding to E box-containing promoter. Critical factor essential for the repressio", "gene_name": "Neurod2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q62414" }, "relationship_type": "protective", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation modulates cell adhesion properties.", "mechanism": "Upregulated in dystrophin-deficient muscle; may stabilize membrane.", "protein": "integrin \u03b17B", "protein_enriched": { "function": "Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (PubMed:8081870). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (PubMed:1", "gene_name": "Itga6", "glycan_count": 11, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G06110VR", "G14669DU", "G23294PN", "G39188ZX", "G62765YT", "G63628AV", "G66538GV", "G02815KT", "G80920RR", "G08290VR", "G49108TO" ], "uniprot_id": "Q61739" }, "relationship_type": "protective", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation influences integrin signaling and adhesion.", "mechanism": "Upregulated in dystrophin-deficient muscle; may aid membrane integrity.", "protein": "integrin \u03b21D", "protein_enriched": { "function": "Integrin alpha-7/beta-1 is the primary laminin receptor on skeletal myoblasts and adult myofibers. During myogenic differentiation, it may induce changes in the shape and mobility of myoblasts, and fa", "gene_name": "Itga7", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G08290VR", "G96368MM", "G05724UK", "G06110VR", "G39188ZX", "G02815KT", "G42124LM", "G60033FS", "G70441OD", "G66538GV", "G05049YU", "G41840AI", "G49108TO" ], "uniprot_id": "Q61738" }, "relationship_type": "protective", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Muscle membrane damage", "glycan_involvement": "Glycosylation affects trafficking and repair function.", "mechanism": "Increased after interval training; involved in membrane repair.", "protein": "dysferlin", "protein_enriched": { "function": "Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements i", "gene_name": "Ptges3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9R0Q7" }, "relationship_type": "protective", "source_pmcid": "PMC12077386" }, { "confidence": "high", "disease": "Muscle membrane damage", "glycan_involvement": "Defective glycosylation impairs membrane stability.", "mechanism": "Loss leads to increased membrane permeability (EBD-positive fibers).", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12077386" }, { "confidence": "high", "disease": "Muscle membrane damage", "glycan_involvement": "Glycosylation required for complex formation.", "mechanism": "Loss leads to increased muscle fiber damage.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "causal", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Muscle fatigue", "glycan_involvement": "Glycosylation affects interaction with extracellular matrix.", "mechanism": "Reduced levels associated with decreased fatigue resistance.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12077386" }, { "confidence": "medium", "disease": "Muscle fatigue", "glycan_involvement": "Glycosylation affects complex stability and muscle function.", "mechanism": "Reduced levels associated with decreased fatigue resistance.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "causal", "source_pmcid": "PMC12077386" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Reduced galactosylation (O-glycosylation defect) in hinge region.", "mechanism": "Aberrant O-glycosylation in hinge region leads to galactose-deficient IgA1 (Gd-IgA1), promoting immune complex formation and mesangial deposition.", "protein": "IgA1", "relationship_type": "causal", "source_pmcid": "PMC12077885" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Global O-glycosylation defect due to enzyme deficiency.", "mechanism": "Loss-of-function variants in GALNT14 reduce GalNAc-T14 activity, impairing O-glycosylation and leading to excess IgA production, defective B cell homing, and glomerular IgA deposition.", "protein": "GalNAc-T14", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity towa", "gene_name": "GALNT12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8IXK2" }, "relationship_type": "causal", "source_pmcid": "PMC12077885" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Polymeric IgA formation involves glycoprotein J-Chain.", "mechanism": "Elevated polymeric IgA (J-Chain containing) in Galnt14-deficient mice correlates with increased glomerular IgA deposition.", "protein": "J-Chain", "protein_enriched": { "function": "Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces dimers and/or larger po", "gene_name": "JCHAIN", "glycan_count": 165, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G00912UN", "G01650EU", "G02030ZB", "G02315DX", "G02815KT", "G03127AL", "G03382KH", "G04657PL", "G04854VP", "G05049YU", "G05724UK", "G05850WN", "G06356OH", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G09197ZW", "G10019LZ", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11314AS", "G11870QZ", "G13694XX", "G14972EH", "G14994KB", "G18647XP", "G22140GZ", "G22310AV", "G22572EH", "G22625SJ", "G22674CI", "G23432EQ", "G23505EP", "G23719VF", "G23863VK", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G31916IQ", "G31936TA", "G32392SM", "G34730YF", "G35029YA", "G35305EF", "G36191CD", "G36379GD", "G37399XV", "G37442IW", "G37868ZX", "G37881RL", "G39188ZX", "G39446WN", "G40574BA", "G40734VV", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G42962KI", "G43157UW", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46687AB", "G46691LC", "G46902YN", "G47644PP", "G47702MW", "G47737VJ", "G47950XN", "G48414YA", "G49018RC", "G49955PK", "G50045TK", "G51413EV", "G52934AK", "G57776ZS", "G57776ZU", "G57818FI", "G58954YZ", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G61627IG", "G61937QU", "G62461SM", "G62595EF", "G62765YT", "G63041LO", "G63980BQ", "G64527OM", "G65184UU", "G66621EA", "G66760KM", "G67324HN", "G70418MS", "G70441OD", "G70619PT", "G71146HJ", "G72291OX", "G72667IM", "G72787SB", "G72790NZ", "G72791KH", "G72797UR", "G74430RZ", "G75983OB", "G76295SF", "G76613WN", "G77669RF", "G78059CC", "G79568CQ", "G79666IR", "G80920RR", "G81282CC", "G81295CK", "G82119TF", "G82463GQ", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84349RE", "G84452RH", "G84467IZ", "G84820NF", "G84862VB", "G85282JO", "G86182NS", "G86880BF", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G91365ZQ", "G91636VS", "G92135MA", "G92275SC", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G98611JV", "G99966GV", "G17015OC" ], "uniprot_id": "P01591" }, "relationship_type": "biomarker", "source_pmcid": "PMC12077885" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation of mucins is defective.", "mechanism": "Reduced O-glycosylation of mucins in Galnt14-deficient mice leads to impaired intestinal mucus barrier, facilitating gut-to-glomerulus inflammatory link.", "protein": "Mucins (intestinal)", "relationship_type": "causal", "source_pmcid": "PMC12077885" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Reduced O-glycosylation on B cell surface glycoproteins.", "mechanism": "Defective O-glycosylation impairs B cell homing to germinal centers, altering IgA production and distribution.", "protein": "Surface glycoproteins on B cells", "relationship_type": "causal", "source_pmcid": "PMC12077885" }, { "confidence": "low", "disease": "Inflammatory bowel disease", "glycan_involvement": "O-glycosylation defect in IgA1.", "mechanism": "Aberrant IgA1 glycosylation may link gut inflammation to glomerular IgA deposition.", "protein": "IgA1", "relationship_type": "biomarker", "source_pmcid": "PMC12077885" }, { "confidence": "low", "disease": "Celiac enteropathy", "glycan_involvement": "O-glycosylation defect in IgA1.", "mechanism": "Similar mechanism as in IBD; defective IgA1 glycosylation may contribute to IgAN in celiac patients.", "protein": "IgA1", "relationship_type": "biomarker", "source_pmcid": "PMC12077885" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Enzyme responsible for initiating O-glycosylation.", "mechanism": "Restoring GalNAc-T14 activity or compensating for its loss could correct O-glycosylation defects and reduce IgAN risk.", "protein": "GalNAc-T14", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity towa", "gene_name": "GALNT12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8IXK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12077885" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation status detectable by lectin binding.", "mechanism": "Reduced PNA lectin staining indicates defective O-glycosylation, correlating with B cell homing defects.", "protein": "Surface glycoproteins on B cells", "relationship_type": "biomarker", "source_pmcid": "PMC12077885" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Global O-glycosylation impairment.", "mechanism": "Autosomal dominant GALNT14 LOF variants intersect multiple pathogenetic steps in IgAN, including IgA overproduction and mucosal barrier defects.", "protein": "GalNAc-T14", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity towa", "gene_name": "GALNT12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8IXK2" }, "relationship_type": "causal", "source_pmcid": "PMC12077885" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin is a glycoprotein; glycosylation may affect stability and membrane localization.", "mechanism": "Mutations in dystrophin gene lead to absence/reduction of dystrophin protein, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation may modulate dystrophin's interaction with extracellular matrix.", "mechanism": "Absence of dystrophin destabilizes sarcolemma, leading to cardiac muscle degeneration and fibrosis.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12087170" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Potential impact on immune recognition and membrane repair; not directly detailed.", "mechanism": "Dystrophin deficiency increases susceptibility to viral and immune-mediated myocarditis.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal/susceptibility", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Glycosylation may affect stability and clearance of troponin I.", "mechanism": "Elevated troponin I indicates acute myocardial injury in myocarditis.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation modulates peptide stability and detection.", "mechanism": "Elevated Nt-ProBNP reflects cardiac dysfunction and heart failure.", "protein": "Nt-ProBNP", "relationship_type": "biomarker", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "CRP is heavily glycosylated, affecting its function and clearance.", "mechanism": "Elevated CRP indicates systemic inflammation associated with myocarditis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation may influence dystrophin's structural role.", "mechanism": "Dystrophin deficiency leads to progressive LV enlargement and wall thinning.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12087170" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Not directly discussed.", "mechanism": "Steroid therapy delays onset of cardiomyopathy by modulating inflammation and possibly dystrophin expression.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12087170" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "No direct glycosylation; clearance depends on glymphatic system and glycoproteins.", "mechanism": "Excessive accumulation of neurotoxic \u03b1-synuclein aggregates drives dopaminergic neurodegeneration.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC12094544" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect localization/function.", "mechanism": "AQP4 facilitates glymphatic clearance of \u03b1-synuclein; impairment leads to its accumulation and worsened PD pathology.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "KLK6 is a glycoprotein; glycosylation may affect secretion/activity.", "mechanism": "KLK6 degrades extracellular \u03b1-synuclein and its fibrils, reducing propagation and toxicity.", "protein": "Kallikrein-6 (KLK6)", "relationship_type": "protective", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "MMPs are glycoproteins; glycosylation modulates activity.", "mechanism": "MMPs participate in proteolytic cascades degrading extracellular \u03b1-synuclein.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "protective", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Plasmin is a glycoprotein; glycosylation affects stability.", "mechanism": "Plasmin degrades aggregated and monomeric \u03b1-synuclein, reducing cell-to-cell spread.", "protein": "Plasmin", "protein_enriched": { "function": "Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ov", "gene_name": "PLG", "glycan_count": 67, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G33791AF", "G48414YA", "G52527GH", "G57321FI", "G53434XO", "G43417UB", "G01614ZM", "G29068FM", "G65562ZE", "G74722FL", "G00912UN", "G06356OH", "G11041DA", "G22310AV", "G36191CD", "G50045TK", "G56749GV", "G59626AS", "G84452RH", "G84467IZ", "G91365ZQ", "G02684WR", "G17015OC", "G23729WG", "G27391WQ", "G58001LT", "G81006GJ", "G82463GQ", "G00776MW", "G03706EO", "G04689DA", "G05724UK", "G06110VR", "G11346GZ", "G12793SR", "G14669DU", "G15956KF", "G20367UY", "G20425TQ", "G22768VO", "G23863VK", "G29857RC", "G39188ZX", "G42039DE", "G47012YE", "G47518TP", "G49108TO", "G49874UX", "G55220VL", "G55661CO", "G56014GC", "G60230HH", "G60452UF", "G66088HZ", "G66538GV", "G70101JE", "G74724QE", "G76675AB", "G78059CC", "G80858MF", "G82348BZ", "G85839YN", "G89186VO", "G90983OS", "G92089QC", "G93656SY", "G96622LK" ], "uniprot_id": "P00747" }, "relationship_type": "protective", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "ApoE is glycosylated; glycosylation affects function.", "mechanism": "Glymphatic transport of apoE is essential for cholesterol transport and synaptic plasticity; dysfunction linked to AD.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12094544" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "AQP4 glycosylation may affect localization/function.", "mechanism": "AQP4 deletion impairs glymphatic clearance of amyloid-\u03b2, increasing its deposition.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Lamp2a is a glycoprotein; glycosylation is essential for lysosomal targeting.", "mechanism": "Lamp2a mediates chaperone-mediated autophagy of \u03b1-synuclein; its dysfunction leads to \u03b1-synuclein accumulation.", "protein": "Lysosomal-associated membrane protein 2 (Lamp2a)", "relationship_type": "protective", "source_pmcid": "PMC12094544" }, { "confidence": "low", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Degrades extracellular \u03b1-synuclein, reducing its pathological accumulation.", "protein": "Insulin-degrading enzyme", "relationship_type": "protective", "source_pmcid": "PMC12094544" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "AQP4 glycosylation may affect localization/function.", "mechanism": "AQP4 dysfunction impairs glymphatic clearance, contributing to epileptogenesis.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12094544" }, { "confidence": "high", "disease": "Neonatal Respiratory Distress Syndrome (NRDS)", "glycan_involvement": "N-glycosylation changes in sialic acid, fucose, and galactose residues on IgG.", "mechanism": "Altered IgG N-glycosylation (increased sialylation and core fucosylation, decreased galactosylation) is associated with NRDS occurrence.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Neonatal Respiratory Distress Syndrome (NRDS)", "glycan_involvement": "Increased sialylation (anti-inflammatory), increased core fucosylation (modulates ADCC), decreased galactosylation (pro-inflammatory).", "mechanism": "Altered IgG glycosylation may modulate inflammation and immune response, contributing to NRDS pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Altered N-glycan composition, including sialylation and galactosylation.", "mechanism": "Distinct IgG N-glycosylation profiles observed in CAD patients, especially women.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT)", "glycan_involvement": "N-glycosylation changes in galactose and sialic acid residues.", "mechanism": "Increased IgG galactosylation and sialylation observed in FNAIT.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma (RCC)", "glycan_involvement": "Increased N-glycan sialylation.", "mechanism": "Elevated IgG sialylation detected in RCC patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Endometrial Cancer (EC)", "glycan_involvement": "Decreased N-glycan sialylation.", "mechanism": "Reduced IgG sialylation observed in EC.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Lyme Disease (LD)", "glycan_involvement": "Elevated galactose residues on N-glycans.", "mechanism": "Increased IgG galactosylation in acute LD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Early Thyroid Cancer (ETC)", "glycan_involvement": "Elevated galactose residues on N-glycans.", "mechanism": "Increased IgG galactosylation in ETC.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Parkinson\u2019s Disease", "glycan_involvement": "Elevated galactose residues on N-glycans.", "mechanism": "Increased IgG galactosylation observed.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 Syndrome", "glycan_involvement": "Reduced galactose residues on N-glycans.", "mechanism": "Decreased IgG galactosylation in GBS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12103862" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "Altered sialylation, galactosylation, and bisecting GlcNAc in IgG N-glycans reflect IR progression", "mechanism": "IgG N-glycosylation profiles correlate with IR severity and inflammatory markers (TNF-\u03b1, IL-6, CRP, adiponectin)", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "Reduced sialylation/galactosylation and increased bisecting GlcNAc drive pro-inflammatory IgG function", "mechanism": "Pro-inflammatory IgG N-glycoforms promote chronic inflammation, contributing to IR development", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "FA2[6]G1 and A2G2S2 (high galactosylation/sialylation) exert anti-inflammatory effects", "mechanism": "Higher levels of FA2[6]G1 and A2G2S2 glycoforms are associated with lower IR risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Stepwise glycan changes track progression from IR to type 2 diabetes", "mechanism": "IgG N-glycosylation patterns (low sialylation/galactosylation, high bisecting GlcNAc) are linked to diabetes severity", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12106251" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Similar glycan alterations as in IR/type 2 diabetes", "mechanism": "Pro-inflammatory IgG N-glycoforms are associated with metabolic syndrome features", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Agalactosylated/asialylated/bisected IgG N-glycans drive immune activation", "mechanism": "IgG N-glycan modifications enhance Fc\u03b3R binding, promoting cytokine release and inflammation", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12106251" }, { "confidence": "medium", "disease": "Insulin resistance (IR)", "glycan_involvement": "Glycoengineering or pharmacological interventions targeting IgG glycosylation", "mechanism": "Modulating IgG N-glycosylation (increasing sialylation/galactosylation) may reduce IR-associated inflammation", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "Alterations detectable in mild IR before CRP elevation", "mechanism": "IgG N-glycan changes precede systemic inflammation, serving as early IR indicators", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "16% of IgG N-glycan effect on IR is mediated by inflammatory markers", "mechanism": "IgG N-glycans mediate IR via direct and indirect (inflammation-mediated) pathways", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modulator", "source_pmcid": "PMC12106251" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Peak FA2[6]G1 in mild IR, decline in severe IR/type 2 diabetes", "mechanism": "FA2[6]G1 glycoform is linked to lower risk of type 2 diabetes", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12106251" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "Increase in Man5, Man7, FA2BG1S1, A2G2S2, FA2BG2S1 glycans in Fab region.", "mechanism": "Altered Fab N-glycosylation at disease onset, especially increased sialylated and oligomannose glycans.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "Decreased FA2[3]BG1 glycan in Fc region.", "mechanism": "Minor decrease in monogalactosylated, bisected, core-fucosylated glycan (FA2[3]BG1) in Fc region.", "protein": "IgG Fc region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Higher Fab N-glycosylation levels detected by lectin affinity.", "mechanism": "Overall Fab glycosylation increased in RA autoantibodies.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Higher Fab N-glycosylation levels detected.", "mechanism": "Fab glycosylation increased in SLE autoantibodies.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "Higher Fab N-glycosylation levels detected.", "mechanism": "Fab glycosylation increased in Myasthenia Gravis autoantibodies.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Pemphigus Vulgaris", "glycan_involvement": "Higher Fab N-glycosylation levels detected.", "mechanism": "Fab glycosylation increased in Pemphigus Vulgaris autoantibodies.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "ANCA-associated Vasculitis", "glycan_involvement": "Higher Fab N-glycosylation levels detected.", "mechanism": "Fab glycosylation increased in ANCA-associated Vasculitis autoantibodies.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Lower galactosylation in Fc region.", "mechanism": "Decreased galactosylation in Fc N-glycans drives overall IgG glycosylation changes in RA.", "protein": "IgG Fc region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "medium", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "Increased sialylated Fab glycans (A2G2S1, A2G2S2, FA2BG1S1, FA2BG2S1).", "mechanism": "Fab sialylation may modulate antigen binding and autoreactive B cell activation, influencing T1D onset.", "protein": "IgG Fab region", "relationship_type": "causal", "source_pmcid": "PMC12108837" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "Increase in oligomannose (Man5, Man7) Fab glycans.", "mechanism": "High mannose Fab glycans (Man5, Man7) increased at T1D onset.", "protein": "IgG Fab region", "relationship_type": "biomarker", "source_pmcid": "PMC12108837" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "O-glycosylation at CTP region affects detection and stability", "mechanism": "hCG is secreted by placental trophoblasts and detected in blood/urine during pregnancy", "protein": "Human chorionic gonadotropin (hCG)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "medium", "disease": "Trophoblastic tumors", "glycan_involvement": "O-glycosylation may influence hCG clearance and immunogenicity", "mechanism": "Elevated hCG levels indicate trophoblastic tumor presence", "protein": "Human chorionic gonadotropin (hCG)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "O-glycosylation at six sites prolongs half-life and activity", "mechanism": "FSH-CTP (corifollitropin alfa) used to stimulate follicle development in infertility treatment", "protein": "Follicle stimulating hormone C-terminal peptide (FSH-CTP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12114138" }, { "confidence": "high", "disease": "Drug immunogenicity/adverse reactions", "glycan_involvement": "O-glycan heterogeneity impacts drug safety and efficacy", "mechanism": "Glycosylation profile affects immunogenicity, efficacy, and clearance of biotherapeutics", "protein": "Follicle stimulating hormone C-terminal peptide (FSH-CTP)", "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "High-density O-GalNAc glycosylation at repeat domains", "mechanism": "Aberrant O-glycosylation of MUC1 is associated with cancer progression", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Multiple O-glycosylation sites affect mucin function", "mechanism": "Altered O-glycosylation of MUC2 linked to cancer and mucosal diseases", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "low", "disease": "Cancer (general)", "glycan_involvement": "Novel O-GlcNAc sites identified", "mechanism": "O-GlcNAcylation regulates transcription factor activity, potentially impacting cancer", "protein": "Serum response factor", "protein_enriched": { "function": "SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as ", "gene_name": "SRF", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "P11831" }, "relationship_type": "biomarker", "source_pmcid": "PMC12114138" }, { "confidence": "high", "disease": "Shigellosis", "glycan_involvement": "Exposure enhanced by truncated O-antigen (wzy knockout)", "mechanism": "Induces robust IgG response; protective immunity in vaccine model", "protein": "IpaB", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Shigellosis", "glycan_involvement": "Exposure enhanced by truncated O-antigen", "mechanism": "Induces IgG response; protective immunity in vaccine model", "protein": "IpaC", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Shigellosis", "glycan_involvement": "Exposure increased by single O-antigen repeat", "mechanism": "Induces IgG response; broad protection against Shigella serotypes", "protein": "PSSP-1 (IcsP C-terminal)", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "medium", "disease": "Shigellosis", "glycan_involvement": "Exposure increased by truncated O-antigen", "mechanism": "Surface-exposed protease; immune response correlates with protection", "protein": "IcsP", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "medium", "disease": "Shigellosis", "glycan_involvement": "Single O-antigen repeat reduces LPS immunogenicity", "mechanism": "Induces IgG response; lower in STM due to wzy knockout", "protein": "LPS (Lipopolysaccharide)", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "medium", "disease": "Shigellosis", "glycan_involvement": "Truncated O-antigen limits OSP exposure", "mechanism": "OSP-specific IgG induced; lower in STM due to wzy knockout", "protein": "OSP (O-specific polysaccharide)", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Campylobacteriosis", "glycan_involvement": "N-glycan expressed on STM surface via biosynthetic locus", "mechanism": "Induces N-glycan-specific IgG; opsonizing antibodies facilitate killing", "protein": "C. jejuni N-glycan heptasaccharide", "relationship_type": "protective", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Shigellosis", "glycan_involvement": "No direct glycosylation, but modulates immune response to glycoproteins", "mechanism": "Adjuvant; enhances IgG response to Shigella antigens and protection", "protein": "dmLT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Campylobacteriosis", "glycan_involvement": "N-glycosylation of surface proteins", "mechanism": "Facilitates adhesion to intestinal epithelial cells; key for pathogenesis", "protein": "C. jejuni N-glycan heptasaccharide", "relationship_type": "causal", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "Shigellosis", "glycan_involvement": "Exposure modulated by O-antigen truncation", "mechanism": "Serum IgG levels to these proteins correlate with vaccine-induced protection", "protein": "IpaB/IpaC/PSSP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12115902" }, { "confidence": "high", "disease": "MRD55", "glycan_involvement": "Impaired dolichol synthesis disrupts N-glycosylation of proteins.", "mechanism": "Loss-of-function NUS1 variants cause truncated NgBR, disrupting dolichol synthesis and protein glycosylation, leading to MRD55.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "medium", "disease": "Autism spectrum disorder (ASD)", "glycan_involvement": "Likely via impaired glycosylation affecting neurodevelopment.", "mechanism": "De novo loss-of-function NUS1 variants (truncating mutations) associated with ASD phenotype.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation", "glycan_involvement": "Direct impairment of N-glycosylation pathway.", "mechanism": "NUS1 mutations disrupt dolichol synthesis, a lipid carrier for N-glycosylation, causing glycosylation defects.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Potential disruption of glycosylation in neuronal proteins.", "mechanism": "Certain NUS1 mutations associated with Parkinson's disease, possibly via glycosylation or lipid metabolism defects.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "medium", "disease": "Dystonia", "glycan_involvement": "Impaired glycosylation in neural tissues.", "mechanism": "NUS1 mutations linked to dystonia, likely via glycosylation pathway disruption.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "high", "disease": "MRD55", "glycan_involvement": "Disrupted N-glycosylation due to defective dolichol synthesis.", "mechanism": "DHDDS forms a complex with NgBR; mutations in either disrupt dolichol synthesis and glycosylation, leading to MRD55-like phenotypes.", "protein": "Dehydrodolichyl diphosphate synthase complex subunit (DHDDS)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "medium", "disease": "Movement disorders", "glycan_involvement": "Indirect effect on glycosylation and lipid metabolism.", "mechanism": "NUS1 haploinsufficiency may cause movement disorders via lysosomal cholesterol accumulation and glycosylation defects.", "protein": "Nogo-B receptor (NgBR, encoded by NUS1)", "relationship_type": "causal", "source_pmcid": "PMC12116661" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "O-GlcNAcylation of intracellular proteins by OGT", "mechanism": "OGT-mediated O-GlcNAcylation aggravates \u03b2-cell death under high glucose, contributing to T1DM progression.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "O-glycosylation (O-GlcNAc) on serine/threonine residues", "mechanism": "Increased global O-GlcNAc modification promotes \u03b2-cell ferroptosis and dysfunction.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Ferroptosis-induced \u03b2-cell death", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGT upregulation increases O-GlcNAcylation, sensitizing \u03b2-cells to ferroptosis under high glucose.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "O-GlcNAcylation", "mechanism": "Inhibition of OGT (e.g., by berberine) reduces \u03b2-cell ferroptosis and may protect against DM progression.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12117152" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGT expression and O-GlcNAc levels are elevated in \u03b2-cells under diabetic conditions.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "biomarker", "source_pmcid": "PMC12117152" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "O-GlcNAc removal", "mechanism": "OGA protein levels were unchanged in high glucose or berberine-treated cells.", "protein": "O-GlcNAcase (OGA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "neutral", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Ferroptosis-induced \u03b2-cell death", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGT inhibition (by berberine) protects \u03b2-cells from ferroptosis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "protective (when inhibited)", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "O-GlcNAcylation", "mechanism": "Elevated O-GlcNAc modification is implicated in DM pathogenesis and complications.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12117152" }, { "confidence": "medium", "disease": "Ferroptosis-induced \u03b2-cell death", "glycan_involvement": "Indirect (not a glycoprotein, but affected by O-GlcNAc pathway)", "mechanism": "GPX4 activity is reduced by high O-GlcNAc/OGT, promoting ferroptosis; berberine restores GPX4 activity.", "protein": "Glutathione peroxidase 4 (GPX4)", "protein_enriched": { "function": "Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce cholesterol hydroperoxide", "gene_name": "GPX4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P36969" }, "relationship_type": "protective", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "Ferroptosis-induced \u03b2-cell death", "glycan_involvement": "O-GlcNAcylation", "mechanism": "OGT overexpression reverses the protective effect of berberine, confirming OGT as a target.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12117152" }, { "confidence": "high", "disease": "UGGT1-CDG", "glycan_involvement": "Defective N-linked glycoprotein reglucosylation and ER quality control.", "mechanism": "Bi-allelic UGGT1 variants impair glucosyltransferase activity, disrupt mRNA splicing, or cause ER retention defects, leading to multisystem disease.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "Neurodevelopmental disorder", "glycan_involvement": "Impaired N-linked glycosylation quality control.", "mechanism": "Loss of UGGT1 function causes impaired protein folding and ER stress, resulting in developmental delay, intellectual disability, and seizures.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "medium", "disease": "Autosomal recessive polycystic kidney disease (ARPKD mimic)", "glycan_involvement": "Defective N-glycosylation affects renal and hepatic protein folding.", "mechanism": "UGGT1 deficiency leads to cystic renal dysplasia and hepatic anomalies mimicking ARPKD.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "MOGS-CDG", "glycan_involvement": "Defective N-linked glycan processing.", "mechanism": "Pathogenic variants in MOGS disrupt glycan trimming, impairing glycoprotein binding to ER chaperones.", "protein": "MOGS", "protein_enriched": { "function": "In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner", "gene_name": "MOGS", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G01650EU", "G05724UK", "G06110VR", "G23294PN", "G39619TI", "G64527OM", "G70101JE" ], "uniprot_id": "Q13724" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "GANAB-CDG", "glycan_involvement": "Impaired N-linked glycan trimming.", "mechanism": "GANAB mutations disrupt glucosidase II activity, affecting glycoprotein folding.", "protein": "GANAB", "protein_enriched": { "function": "Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubM", "gene_name": "GANAB", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G81315DD" ], "uniprot_id": "Q14697" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "MAN1B1-CDG (Rafiq syndrome)", "glycan_involvement": "Defective N-glycan processing and degradation signaling.", "mechanism": "MAN1B1 deficiency impairs mannose trimming, leading to ERAD defects.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "EDEM3-CDG", "glycan_involvement": "Impaired N-glycan trimming for ERAD.", "mechanism": "EDEM3 mutations disrupt ER mannosidase activity, affecting glycoprotein degradation.", "protein": "EDEM3", "protein_enriched": { "function": "", "gene_name": "STK3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NBU1" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "medium", "disease": "Congenital heart malformations", "glycan_involvement": "Defective N-glycosylation impacts cardiac protein folding.", "mechanism": "UGGT1 loss-of-function variants associated with congenital heart defects in severe cases.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "medium", "disease": "Skeletal abnormalities", "glycan_involvement": "Impaired glycoprotein folding in skeletal development.", "mechanism": "UGGT1 deficiency leads to skeletal deformities including scoliosis and syndactyly.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Defective N-glycosylation in neuronal proteins.", "mechanism": "UGGT1-CDG patients frequently present with seizures due to ER stress and neuronal dysfunction.", "protein": "UGGT1", "protein_enriched": { "function": "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic retic", "gene_name": "UGGT1", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO", "G41247ZX", "G43769HG", "G60033FS", "G65184UU", "G57321FI", "G49108TO", "G01485JJ", "G02815KT", "G05724UK", "G06110VR", "G14994KB", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G45504EY", "G50282JC", "G57317CE", "G57776ZU", "G62765YT", "G63980BQ", "G70101JE", "G74724QE", "G84349RE", "G85269DF", "G90575OW", "G92050GC", "G92275SC", "G95177YH" ], "uniprot_id": "Q9NYU2" }, "relationship_type": "causal", "source_pmcid": "PMC12120171" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Altered O-glycosylation (Core 1 vs Core 2), increased sialylation in tumor-associated MUC1.", "mechanism": "Overexpressed in BC, promotes proliferation, metastasis, immune evasion, and chemoresistance; targeted by vaccines and monoclonal antibodies.", "protein": "MUC1 (CA 15-3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation modulates ligand binding (HA, ECM proteins) and cell adhesion.", "mechanism": "Marker of tumor-initiating cells; overexpression linked to poor prognosis and metastasis; antibody targeting reduces tumor growth.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation required for selectin binding and immune modulation.", "mechanism": "Elevated in BC, correlates with aggressiveness and metastasis; regulates immune cell trafficking.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Sialylation affects immune cell interactions.", "mechanism": "Aberrant expression in BC; may contribute to immune escape and tumor classification.", "protein": "CD43 (Sialophorin)", "protein_enriched": { "function": "Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regula", "gene_name": "SPN", "glycan_count": 16, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G11457RF", "G46748BU", "G56682BC", "G57321FI", "G60890ZT", "G65562ZE", "G49108TO", "G43417UB", "G19399OS", "G29931IJ", "G37891WT", "G59970QL", "G74722FL", "G81006GJ" ], "uniprot_id": "P16150" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Chondroitin sulfate glycosylation critical for function.", "mechanism": "Overexpressed in BC; promotes angiogenesis and tumor progression; targeted by antibodies and CAR constructs.", "protein": "CSPG4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Acts on heparan sulfate glycosylation in proteoglycans.", "mechanism": "Cleaves HS chains, remodels ECM, promotes metastasis and chemoresistance; inhibitors show anticancer effects.", "protein": "Heparanase (HPSE)", "protein_enriched": { "function": "Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell ", "gene_name": "PLXNA1", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G27058EU", "G40926MX", "G41071NU", "G31852PQ", "G80920RR", "G62765YT", "G57321FI", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9UIW2" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "medium", "disease": "Drug-resistant Breast Cancer", "glycan_involvement": "Synthesizes glucosylceramide, precursor for complex glycolipids.", "mechanism": "Overexpression linked to drug resistance and metastatic disease; high mRNA associated with longer survival.", "protein": "UGCG (GlcCer synthase)", "protein_enriched": { "function": "Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates (PubMed:16214399, PubMed:18768481, PubMed:28420705, PubMed:32433610", "gene_name": "DGAT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O75907" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Metastatic Breast Cancer", "glycan_involvement": "Galactosylation of ceramide affects cell survival.", "mechanism": "High expression in basal-like BC; GalCer accumulation inhibits apoptosis, predicts poor prognosis.", "protein": "UGT8 (GalCer synthase)", "protein_enriched": { "function": "Oxidoreductase that catalyzes the last step of the cholesterol synthesis pathway, which transforms cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol,7-DHC) into cholesterol by reducing the C7-C8 double", "gene_name": "DHCR7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBM7" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "O-glycosylation (sialylation) of mucins and other proteins.", "mechanism": "Overexpression forms sialyl-Tn antigen, promotes proliferation, migration, invasion; knockdown reduces metastasis.", "protein": "ST6GALNAC4", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Breast Cancer Stem Cells", "glycan_involvement": "Sialylation of gangliosides (GD3 to GD2).", "mechanism": "Synthesizes GD2 ganglioside, marker of BC stem cells; inhibition suppresses invasion and metastasis.", "protein": "GD3S (ST8SIA1)", "protein_enriched": { "function": "Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan protein acceptor through alpha", "gene_name": "ST8SIA4", "glycan_count": 5, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G57321FI", "G92551JA", "G80920RR", "G83460ZZ" ], "uniprot_id": "Q92187" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122162" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "CD6 is a heavily glycosylated membrane protein; glycosylation affects ligand binding and immune modulation.", "mechanism": "Regulates T cell activation and proliferation; higher levels reduce inflammation and bacterial burden.", "protein": "T-cell surface glycoprotein CD6 isoform", "protein_enriched": { "function": "Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166 (PubMed:15048703, PubMed:15294938, PubMed:16352806, PubMed:16914752, PubMed:", "gene_name": "CD6", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27058EU", "G31852PQ" ], "uniprot_id": "P30203" }, "relationship_type": "protective", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "N-glycosylation required for receptor function and cell surface expression.", "mechanism": "Mediates IL-18 signaling, promoting pro-inflammatory cytokine release and tissue inflammation.", "protein": "Interleukin-18 receptor 1", "protein_enriched": { "function": "Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B (PubMed:14528293, PubMed:25261253, PubMed:25500532, PubMed:37993714, PubMed:8", "gene_name": "IL18R1", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22768VO", "G34442SS", "G80920RR", "G22573RC", "G00395TQ", "G57321FI" ], "uniprot_id": "Q13478" }, "relationship_type": "causal", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "Glycosylation may modulate secretion and stability.", "mechanism": "Acts as an alarmin cytokine, amplifies type 2 inflammation and immune cell recruitment.", "protein": "Interleukin-33", "protein_enriched": { "function": "Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016, PubMed:19841166). Involved in the ma", "gene_name": "IL33", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95760" }, "relationship_type": "causal", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "N-glycosylation influences secretion and receptor binding.", "mechanism": "Regulates T cell homeostasis; elevated levels linked to chronic inflammation and tissue invasion.", "protein": "Interleukin-7", "protein_enriched": { "function": "Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintain", "gene_name": "IL7", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P13232" }, "relationship_type": "causal", "source_pmcid": "PMC12122772" }, { "confidence": "medium", "disease": "Perianal abscess", "glycan_involvement": "Glycosylation affects receptor interaction and cytokine activity.", "mechanism": "Promotes pro-inflammatory cytokine production and immune cell infiltration.", "protein": "Tumor necrosis factor ligand superfamily member 12 (TWEAK)", "protein_enriched": { "function": "Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also i", "gene_name": "TNFSF12", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "O43508" }, "relationship_type": "causal", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "N-glycosylation required for secretion and bioactivity.", "mechanism": "Enhances T and B cell proliferation and immune regulation, reducing abscess recurrence.", "protein": "Interleukin-2", "relationship_type": "protective", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Perianal abscess", "glycan_involvement": "N-glycosylation critical for cell surface expression and immune checkpoint function.", "mechanism": "Suppresses excessive immune activation, preserves tissue integrity during inflammation.", "protein": "Programmed cell death 1 ligand 1 (PD-L1)", "relationship_type": "protective", "source_pmcid": "PMC12122772" }, { "confidence": "high", "disease": "Diabetic wound healing disorder", "glycan_involvement": "O-GlcNAcylation stabilizes HMGB1, enhancing its pro-NET activity.", "mechanism": "O-GlcNAcylated HMGB1 promotes NET formation, leading to impaired fibroblast function and delayed wound healing.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "Diabetic wound healing disorder", "glycan_involvement": "GLUT1 supplies substrate for O-GlcNAcylation via hexosamine biosynthetic pathway.", "mechanism": "GLUT1-mediated glucose uptake increases O-GlcNAcylation of HMGB1, driving NET formation and fibroblast dysfunction.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "Fibroblast inflammatory injury", "glycan_involvement": "O-GlcNAcylation of HMGB1 increases its stability and NET-inducing activity.", "mechanism": "NETs containing O-GlcNAcylated HMGB1 induce fibroblast inflammation and reduce viability/migration.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "Fibroblast inflammatory injury", "glycan_involvement": "GLUT1-driven O-GlcNAcylation of HMGB1 is required for NET formation.", "mechanism": "GLUT1 upregulation in neutrophils enhances HMGB1 O-GlcNAcylation, promoting NET-mediated fibroblast damage.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "NET-driven inflammation", "glycan_involvement": "O-GlcNAcylation enhances HMGB1's ability to activate TLR4.", "mechanism": "O-GlcNAcylated HMGB1 activates TLR4 signaling, leading to NET formation and inflammatory cytokine release.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "NET-driven inflammation", "glycan_involvement": "TLR4 is activated by O-GlcNAcylated HMGB1.", "mechanism": "TLR4 signaling is required for HMGB1-induced NET formation and downstream inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12122836" }, { "confidence": "medium", "disease": "NET-driven inflammation", "glycan_involvement": "Indirect; Cit-H3 levels increase with HMGB1 O-GlcNAcylation.", "mechanism": "Cit-H3 is a marker of NET formation, which correlates with tissue inflammation in diabetes.", "protein": "Cit-H3", "protein_enriched": { "function": "Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromati", "gene_name": "H3-3A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84243" }, "relationship_type": "biomarker", "source_pmcid": "PMC12122836" }, { "confidence": "medium", "disease": "NET-driven inflammation", "glycan_involvement": "Indirect; MPO levels increase with NET formation driven by glycosylated HMGB1.", "mechanism": "MPO is a NET marker elevated in diabetic inflammation.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC12122836" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "O-GlcNAcylation is increased in diabetes, stabilizing HMGB1.", "mechanism": "Elevated O-GlcNAcylated HMGB1 is associated with hyperglycemia and diabetic complications.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12122836" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Targeting GLUT1 limits substrate for O-GlcNAcylation.", "mechanism": "GLUT1 inhibition reduces HMGB1 O-GlcNAcylation and NET formation, ameliorating fibroblast injury.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122836" }, { "confidence": "high", "disease": "Hashimoto's encephalopathy", "glycan_involvement": "Thyroglobulin is a glycoprotein; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Elevated anti-thyroglobulin antibodies are associated with HE and serve as a diagnostic marker.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123474" }, { "confidence": "high", "disease": "Hashimoto's encephalopathy", "glycan_involvement": "Thyroid peroxidase is glycosylated; glycan structures may influence immune recognition.", "mechanism": "Elevated anti-thyroid peroxidase antibodies are strongly associated with HE and are used diagnostically.", "protein": "Thyroid peroxidase", "relationship_type": "biomarker", "source_pmcid": "PMC12123474" }, { "confidence": "high", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Glycosylation of thyroglobulin modulates its immunogenicity.", "mechanism": "Autoantibodies against thyroglobulin contribute to thyroid tissue damage in Hashimoto's thyroiditis.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC12123474" }, { "confidence": "high", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Glycosylation may affect TPO's antigenic epitopes.", "mechanism": "Autoantibodies against thyroid peroxidase mediate thyroid cell destruction in Hashimoto's thyroiditis.", "protein": "Thyroid peroxidase", "relationship_type": "causal", "source_pmcid": "PMC12123474" }, { "confidence": "medium", "disease": "Hashimoto's encephalopathy", "glycan_involvement": "Glycosylation may influence antibody binding and therapeutic response.", "mechanism": "Reduction of anti-thyroglobulin antibodies via immunosuppression improves HE symptoms.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123474" }, { "confidence": "medium", "disease": "Hashimoto's encephalopathy", "glycan_involvement": "Glycan structures may modulate immune response to TPO.", "mechanism": "Lowering anti-TPO antibody levels correlates with clinical improvement in HE.", "protein": "Thyroid peroxidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123474" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Indirect; HDAC4 regulates glycoprotein GLUT4 transcription.", "mechanism": "HDAC4 represses GLUT4 and FOXO1, impairing insulin signaling and glucose metabolism.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123801" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "GLUT4 is N-glycosylated, affecting its trafficking and function.", "mechanism": "Reduced GLUT4 membrane translocation leads to insulin resistance and hyperglycemia.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Possible O-glycosylation modulates FOXO1 activity.", "mechanism": "HDAC4 deacetylates FOXO1, promoting gluconeogenic gene expression and hyperglycemia.", "protein": "FOXO1", "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Indirect; HDAC4 deacetylates nephrin, an N-glycosylated protein.", "mechanism": "HDAC4 upregulation in podocytes decreases autophagy and promotes apoptosis via STAT1 deacetylation.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Nephrin N-glycosylation is essential for stability and filtration barrier.", "mechanism": "HDAC4-mediated deacetylation and degradation of nephrin impairs podocyte function.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "high", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "O-GlcNAc glycosylation at Ser642 generates protective HDAC4 fragment.", "mechanism": "Phosphorylated HDAC4 promotes MEF2-driven hypertrophy; O-GlcNAc-modified HDAC4 fragment is cardioprotective.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "dual (causal/protective)", "source_pmcid": "PMC12123801" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "HDAC4/CaMKII suppresses MEF2C, impairing angiogenesis and exacerbating cardiac dysfunction.", "protein": "MEF2C", "protein_enriched": { "function": "Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involve", "gene_name": "MEF2C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q06413" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "medium", "disease": "Diabetes Osteoporosis", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "HDAC4 inhibition by miR-26a-5p in stem cell-derived EVs improves osteoclast activity and bone microstructure.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "medium", "disease": "Diabetic Encephalopathy", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "Elevated HDAC4 activates JNK pathway, increasing hippocampal neuronal apoptosis.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "medium", "disease": "Diabetic Wounds", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "HDAC4 upregulation enhances NLRP3-mediated pyroptosis, impairing wound healing.", "protein": "HDAC4", "protein_enriched": { "function": "Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:3853", "gene_name": "HDAC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G68490OW" ], "uniprot_id": "Q9UBN7" }, "relationship_type": "causal", "source_pmcid": "PMC12123801" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "MAN2A2 mediates glycosylation of lipids/proteins; altered glycosylation impacts cell signaling and membrane properties", "mechanism": "DNA methylation of MAN2A2 associated with T2D onset", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "Disrupted glycosylation promotes atherosclerosis and endothelial dysfunction", "mechanism": "MAN2A2 methylation correlates with myocardial infarction risk", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "ABCA1 is a glycoprotein; glycosylation affects its stability and function in HDL formation", "mechanism": "ABCA1 hypermethylation impairs cholesterol efflux, increasing CVD risk", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "causal", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation modulates ABCG1 trafficking and cholesterol efflux", "mechanism": "ABCG1 methylation increases MI risk by impairing cholesterol transport", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "SERCA2a glycosylation affects protein folding and cardiac function", "mechanism": "Promoter methylation reduces SERCA2a expression, causing calcium overload and diastolic heart failure", "protein": "SERCA2a", "relationship_type": "causal", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "LMF1 chaperones glycoprotein lipases, affecting triglyceride metabolism", "mechanism": "LMF1 promoter methylation links lipid dysregulation to cardiac complications in T2D", "protein": "LMF1", "protein_enriched": { "function": "Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:1", "gene_name": "AFG3L2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4W6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Coronary Heart Disease", "glycan_involvement": "SREBF1 regulates genes involved in glycoprotein and lipid synthesis", "mechanism": "SREBF1 methylation increases risk of CHD via dysregulated lipid metabolism", "protein": "SREBF1", "protein_enriched": { "function": "Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations", "gene_name": "SREBF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P36956" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Acute Coronary Syndromes", "glycan_involvement": "TXNIP glycosylation may affect its stability and redox signaling", "mechanism": "TXNIP methylation at cg19693031 is a marker for T2D patients with acute coronary syndromes", "protein": "TXNIP", "relationship_type": "biomarker", "source_pmcid": "PMC12124063" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "FZD5 is a glycoprotein receptor; glycosylation modulates ligand binding and signaling", "mechanism": "FZD5 promoter methylation disrupts Wnt signaling, contributing to vascular dysfunction in T2D", "protein": "FZD5", "protein_enriched": { "function": "Receptor for Wnt proteins (PubMed:10097073, PubMed:20530549, PubMed:26908622, PubMed:9054360). Functions in the canonical Wnt/beta-catenin signaling pathway. In vitro activates WNT2, WNT10B, WNT5A, bu", "gene_name": "FZD5", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G43417UB" ], "uniprot_id": "Q13467" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "Endothelial Dysfunction", "glycan_involvement": "PPARG regulates genes involved in glycoprotein metabolism and vascular health", "mechanism": "PPARG hypermethylation reduces expression, impairing metabolic and anti-inflammatory functions, increasing CVD risk", "protein": "PPARG", "relationship_type": "causal", "source_pmcid": "PMC12124063" }, { "confidence": "high", "disease": "All-cause dementia", "glycan_involvement": "Transmembrane glycoprotein; glycosylation likely mediates cell adhesion and immune signaling.", "mechanism": "Higher plasma and CSF IGDCC4 abundance causally linked to reduced dementia risk and preserved medial temporal brain volume.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12124368" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect extracellular domain interactions and neuroprotection.", "mechanism": "Higher IGDCC4 associated with lower odds of amyloid-\u03b2 positivity and better cognitive performance.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12124368" }, { "confidence": "high", "disease": "Brain atrophy", "glycan_involvement": "Glycosylation supports axonal integrity and cell adhesion.", "mechanism": "Genetic variation increasing IGDCC4 abundance linked to maintenance of medial temporal brain volume.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12124368" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation may modulate neurovascular interactions.", "mechanism": "Higher IGDCC4 shows trend toward reduced vascular dementia risk.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12124368" }, { "confidence": "medium", "disease": "All-cause dementia", "glycan_involvement": "Membrane glycoprotein; glycosylation affects immune checkpoint function.", "mechanism": "Down-regulation of LAG3 with viral antibodies causally linked to increased dementia risk.", "protein": "LAG3", "relationship_type": "causal/pathogenic", "source_pmcid": "PMC12124368" }, { "confidence": "medium", "disease": "All-cause dementia", "glycan_involvement": "Soluble glycoprotein; glycosylation may influence antioxidant activity.", "mechanism": "Up-regulation of GSS with viral antibodies causally linked to reduced dementia risk.", "protein": "GSS", "relationship_type": "causal/protective", "source_pmcid": "PMC12124368" }, { "confidence": "medium", "disease": "All-cause dementia", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect protease activity.", "mechanism": "Down-regulation of PRSS27 with viral antibodies causally linked to increased dementia risk.", "protein": "PRSS27", "protein_enriched": { "function": "", "gene_name": "C11orf68", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H3H3" }, "relationship_type": "causal/pathogenic", "source_pmcid": "PMC12124368" }, { "confidence": "medium", "disease": "All-cause dementia", "glycan_involvement": "Putative glycoprotein; glycosylation status not fully characterized.", "mechanism": "Down-regulation of C2ORF66 with viral antibodies causally linked to increased dementia risk.", "protein": "C2ORF66", "relationship_type": "causal/pathogenic", "source_pmcid": "PMC12124368" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation may facilitate neuroprotective signaling.", "mechanism": "Higher IGDCC4 associated with better performance in multiple cognitive domains.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12124368" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation impacts cell adhesion and axonal guidance.", "mechanism": "Down-regulation of IGDCC4 in neurons and neurovascular cells in AD brains and mouse models suggests loss contributes to pathology.", "protein": "IGDCC4", "protein_enriched": { "function": "Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary ", "gene_name": "IGSF1", "glycan_count": 4, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G27126ED", "G40574BA", "G80920RR" ], "uniprot_id": "Q8N6C5" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12124368" }, { "confidence": "high", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation is required for its cell surface expression and ligand binding.", "mechanism": "PD-1 is targeted by inhibitors (cemiplimab, pembrolizumab, nivolumab) to enhance anti-tumor immunity in cSCC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124471" }, { "confidence": "high", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "PD-L1 glycosylation modulates its stability and interaction with PD-1.", "mechanism": "PD-L1 is targeted by inhibitors (atezolizumab, avelumab) to block immune evasion by tumor cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "EGFR is heavily N-glycosylated, which affects ligand binding and receptor activation.", "mechanism": "EGFR inhibitors (cetuximab) are used alone or in combination with PD-1/PD-L1 inhibitors to treat advanced cSCC.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "As a viral glycoprotein, glycosylation is essential for fusogenic activity.", "mechanism": "GALV-GP R\u2013 is expressed by oncolytic virus RP1 to induce tumor cell fusion and enhance immune response.", "protein": "GALV-GP R\u2013", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12124471" }, { "confidence": "low", "disease": "Chronic lymphocytic leukemia", "glycan_involvement": "PD-1 glycosylation affects immune checkpoint function.", "mechanism": "Patients with CLL included in adjuvant cemiplimab trials for cSCC, suggesting PD-1 targeting may be relevant.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Autoimmune diseases (e.g., rheumatoid arthritis, psoriasis)", "glycan_involvement": "Glycosylation status may influence PD-1 function and immune tolerance.", "mechanism": "PD-1 inhibitors can trigger immune-related adverse events and flares in autoimmune disease patients.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Renal transplant rejection", "glycan_involvement": "Glycosylation of PD-1 may affect immune regulation in transplantation.", "mechanism": "PD-1 blockade can lead to allograft rejection in renal transplant recipients treated for cSCC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "CD3 is a glycoprotein; glycosylation is important for T cell receptor function.", "mechanism": "Increased CD3+ T cells in tumor tissue associated with response to cemiplimab in kidney transplant recipients.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "CD8 glycosylation affects T cell activation and antigen recognition.", "mechanism": "Increased CD8+ T cells in tumor tissue associated with response to cemiplimab.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124471" }, { "confidence": "medium", "disease": "Cutaneous squamous cell carcinoma (cSCC)", "glycan_involvement": "Glycosylation of PD-L1 can affect antibody recognition and immune evasion.", "mechanism": "PD-L1 expression is a predictive biomarker for response to PD-1/PD-L1 inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124471" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease", "glycan_involvement": "Glycosylation of MOG affects antigenicity and antibody recognition.", "mechanism": "Autoantibodies against MOG indicate disease presence and help differentiate from MS and NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "MOG antibodies are used to exclude MS and identify MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder", "glycan_involvement": "Glycosylation influences antibody binding and pathogenicity.", "mechanism": "AQP4 antibodies are diagnostic for NMOSD and distinguish it from MS.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder", "glycan_involvement": "Glycosylation affects epitope exposure.", "mechanism": "MOG antibodies help differentiate NMOSD from MOGAD and MS.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "low", "disease": "Clinically Isolated Syndrome", "glycan_involvement": "Glycosylation may affect early immune response.", "mechanism": "MOG antibodies may be present in CIS, indicating risk for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "low", "disease": "Radiologically Isolated Syndrome", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "MOG antibodies may help stratify RIS patients at risk for demyelinating disease.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects antibody specificity.", "mechanism": "Absence of AQP4 antibodies helps exclude NMOSD in MS diagnosis.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124479" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation of G is essential for proper folding, antigenicity, and immunogenicity.", "mechanism": "Glycoprotein is the major antigenic determinant for neutralizing antibodies and is targeted in vaccine formulations.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects detection and quantification in immunoassays.", "mechanism": "Glycoprotein content is measured in vaccine quality control to ensure immunogenic potency.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "biomarker", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "No direct glycosylation involvement; exposure is structural.", "mechanism": "Exposed N serves as a quantitative marker for viral particle integrity in vaccine quality control.", "protein": "Rabies virus nucleoprotein (N)", "protein_enriched": { "function": "Non catalytic polymerase cofactor and regulatory protein that plays a role in viral transcription and replication. Stabilizes the RNA polymerase L to the N-RNA template and binds the soluble protein N", "gene_name": "P", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06747" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation required for immunogenicity and proper antigen presentation.", "mechanism": "Induces protective immunity via neutralizing antibody response.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "protective", "source_pmcid": "PMC12124496" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation modulates receptor interaction and infectivity.", "mechanism": "G mediates viral entry into host cells via receptor binding and membrane fusion.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "No direct glycosylation; structural exposure is key.", "mechanism": "Detection of exposed N indicates loss of viral particle integrity, a critical parameter in vaccine safety and efficacy.", "protein": "Rabies virus nucleoprotein (N)", "protein_enriched": { "function": "Non catalytic polymerase cofactor and regulatory protein that plays a role in viral transcription and replication. Stabilizes the RNA polymerase L to the N-RNA template and binds the soluble protein N", "gene_name": "P", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06747" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects assay sensitivity and specificity.", "mechanism": "Used in immunoassays for batch release and potency testing of vaccines.", "protein": "Rabies virus glycoprotein (G)", "relationship_type": "biomarker", "source_pmcid": "PMC12124496" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "GPC is processed into glycoproteins (Gn, Gc) via host glycosylation and proteolytic cleavage.", "mechanism": "GPC elicits neutralizing antibodies and T cell responses; used as vaccine antigen.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Gc is a glycoprotein; glycosylation affects antigenicity and processing.", "mechanism": "Gc contains conserved T cell epitopes; targeted by vaccine-induced immunity.", "protein": "CCHFV Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125290" }, { "confidence": "medium", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Gn is glycosylated; glycosylation may affect immune recognition.", "mechanism": "Gn is a structural glycoprotein; elicits low/undetectable antibody responses in vaccine studies.", "protein": "CCHFV Gn glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125290" }, { "confidence": "medium", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "GP38 is a secreted glycoprotein; glycosylation may influence immunogenicity.", "mechanism": "GP38-specific antibodies induced by GPC-based vaccines; may contribute to protection, but are strain-specific.", "protein": "CCHFV GP38", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "NP is not a glycoprotein; protection is independent of glycosylation.", "mechanism": "NP is highly conserved and immunogenic; NP-based vaccines elicit non-neutralizing antibodies that protect via Fc-mediated mechanisms.", "protein": "CCHFV nucleoprotein (NP)", "relationship_type": "protective", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation and proteolytic cleavage of GPC are required for functional Gn/Gc formation.", "mechanism": "GPC mediates viral entry and fusion; essential for CCHFV infectivity and pathogenesis.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "EBOV-GP contains immunodominant glycan cap and mucin-like domain; glycosylation modulates immune response.", "mechanism": "EBOV-GP is used in VSV-based vaccine platforms; elicits protective immunity.", "protein": "Ebola virus glycoprotein (EBOV-GP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation sites and processing influence antigenicity and strain specificity.", "mechanism": "GPC-based vaccines confer partial protection, especially against homologous strains; efficacy reduced by sequence diversity.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12125290" }, { "confidence": "medium", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Not directly related to glycosylation.", "mechanism": "TRIM21 mediates intracellular antibody-dependent protection against CCHFV via NP recognition.", "protein": "TRIM21", "relationship_type": "protective", "source_pmcid": "PMC12125290" }, { "confidence": "medium", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation may affect antigenicity and strain specificity.", "mechanism": "GP38-specific antibody responses indicate vaccine-induced immunity; may correlate with strain-specific protection.", "protein": "CCHFV GP38", "relationship_type": "biomarker", "source_pmcid": "PMC12125290" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies (IgG/IgM) against \u03b22-glycoprotein I are diagnostic markers for APS.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "Anti-\u03b22GPI antibodies promote thrombosis via endothelial activation and coagulation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12125344" }, { "confidence": "medium", "disease": "Pregnancy morbidity", "glycan_involvement": "Glycosylation may influence placental binding and immune response.", "mechanism": "Anti-\u03b22GPI antibodies impair placental function, leading to miscarriage/fetal death.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12125344" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Cardiolipin forms complexes with glycoproteins (e.g., \u03b22GPI) for antibody recognition.", "mechanism": "Autoantibodies (IgG/IgM) against cardiolipin are diagnostic for APS.", "protein": "Cardiolipin (as antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Complex formation with glycoproteins is essential for pathogenic antibody binding.", "mechanism": "Anti-cardiolipin antibodies contribute to thrombosis via coagulation pathway activation.", "protein": "Cardiolipin (as antigen)", "relationship_type": "causal", "source_pmcid": "PMC12125344" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation may affect cell surface localization and antibody binding.", "mechanism": "Anti-annexin A5 antibodies are associated with APS clinical manifestations.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Anti-annexin A2 antibodies are linked to APS and its clinical events.", "protein": "Annexin A2", "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "Anti-phosphatidylserine/prothrombin antibodies are associated with APS.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "low", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Anti-plasmin antibodies are associated with APS clinical manifestations.", "protein": "Plasmin", "protein_enriched": { "function": "Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ov", "gene_name": "PLG", "glycan_count": 67, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G33791AF", "G48414YA", "G52527GH", "G57321FI", "G53434XO", "G43417UB", "G01614ZM", "G29068FM", "G65562ZE", "G74722FL", "G00912UN", "G06356OH", "G11041DA", "G22310AV", "G36191CD", "G50045TK", "G56749GV", "G59626AS", "G84452RH", "G84467IZ", "G91365ZQ", "G02684WR", "G17015OC", "G23729WG", "G27391WQ", "G58001LT", "G81006GJ", "G82463GQ", "G00776MW", "G03706EO", "G04689DA", "G05724UK", "G06110VR", "G11346GZ", "G12793SR", "G14669DU", "G15956KF", "G20367UY", "G20425TQ", "G22768VO", "G23863VK", "G29857RC", "G39188ZX", "G42039DE", "G47012YE", "G47518TP", "G49108TO", "G49874UX", "G55220VL", "G55661CO", "G56014GC", "G60230HH", "G60452UF", "G66088HZ", "G66538GV", "G70101JE", "G74724QE", "G76675AB", "G78059CC", "G80858MF", "G82348BZ", "G85839YN", "G89186VO", "G90983OS", "G92089QC", "G93656SY", "G96622LK" ], "uniprot_id": "P00747" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125344" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may modulate immune-mediated platelet destruction.", "mechanism": "Anti-\u03b22GPI antibodies are associated with APS-related thrombocytopenia.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12125344" }, { "confidence": "high", "disease": "Parkinson's Disease with Cognitive Impairment (PDCI)", "glycan_involvement": "Glycosylation required for secretion and function; altered levels may reflect glycan-dependent BBB breach.", "mechanism": "Elevated CSF fibrinogen induces motor and cognitive deficits, DA neuron loss, and hippocampal/subicular hypertrophy in mice.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12125439" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation essential for stability and interaction with BBB/endothelial cells.", "mechanism": "High fibrinogen levels cause neurodegeneration in SNpc and striatum, mimicking PD pathology.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation influences fibrinogen aggregation and deposition.", "mechanism": "Fibrinogen deposition exacerbates AD pathology and amyloid-\u03b2 accumulation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12125439" }, { "confidence": "high", "disease": "Parkinson's Disease with Cognitive Impairment (PDCI)", "glycan_involvement": "CFH glycosylation modulates complement regulation and neuroinflammation.", "mechanism": "Elevated CFH in CSF induces motor and cognitive deficits, neuronal degeneration, and gut architectural changes in mice.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation required for CFH function in complement regulation.", "mechanism": "CFH elevation indicates neuroinflammation, a key PD pathogenic factor.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation affects CFH stability and immune interactions.", "mechanism": "Increased CFH in CSF/serum acts as compensatory mechanism against complement overactivation.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation influences epithelial interactions and mucosal integrity.", "mechanism": "Fibrinogen supplementation alters colonic architecture, potentially contributing to gut inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation modulates CFH's immune regulatory role in gut.", "mechanism": "CFH elevation leads to increased colonic folds and muscularis thickening, suggesting inflammatory response.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. 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Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation status may affect therapeutic efficacy.", "mechanism": "Modulating CFH levels could regulate neuroinflammation in PD.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125439" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Lectin binds specific glycan structures, modulating immune response", "mechanism": "Immunomodulation and cytotoxic activity against breast cancer cells", "protein": "Lectin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125795" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects protein stability and immune recognition", "mechanism": "Modulates cytokine production, enhances immune surveillance", "protein": "Fungal Immunomodulatory Protein (FIP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125795" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Branched glycan structures enhance immunomodulatory activity", "mechanism": "Antioxidant and immunomodulatory effects, supports recovery post-chemotherapy", "protein": "Branched chain 1,3,6-glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate enzyme activity and stability", "mechanism": "May contribute to anti-tumor activity via proteolytic processing of extracellular matrix", "protein": "Serine Protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Chemotherapy-induced fatigue", "glycan_involvement": "Lectin-glycan interactions modulate immune cell activation", "mechanism": "Immunomodulation may reduce inflammation and fatigue", "protein": "Lectin", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Chemotherapy-induced cognitive impairment", "glycan_involvement": "Branched glycans enhance antioxidant activity", "mechanism": "Antioxidant properties may protect against mitochondrial dysfunction", "protein": "Branched chain 1,3,6-glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Chemotherapy-induced fatigue", "glycan_involvement": "Glycosylation affects immune modulation", "mechanism": "Modulates immune response, potentially reducing fatigue", "protein": "Fungal Immunomodulatory Protein (FIP)", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "medium", "disease": "Diabetes (AGEs-related)", "glycan_involvement": "Glycoprotein structure may interact with AGEs pathways", "mechanism": "Reduces advanced glycation end products (AGEs), improves mitochondrial function", "protein": "Branched chain 1,3,6-glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Oxidative stress-related conditions", "glycan_involvement": "Lectin-glycan binding may enhance antioxidant defense", "mechanism": "Antioxidant activity reduces ROS and oxidative damage", "protein": "Lectin", "relationship_type": "protective", "source_pmcid": "PMC12125795" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Specific glycan linkages modulate immune activity", "mechanism": "May contribute to immunomodulatory and anti-tumor effects", "protein": "1,4,6-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125795" }, { "confidence": "high", "disease": "Herpes zoster (shingles)", "glycan_involvement": "gE is heavily glycosylated, which is essential for its function in viral infectivity and immune modulation.", "mechanism": "gE mediates viral entry, cell-to-cell spread, and immune evasion during VZV reactivation.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "high", "disease": "Post-herpetic neuralgia (PHN)", "glycan_involvement": "Glycosylation of gE affects neurotropism and immune escape, contributing to neuronal injury.", "mechanism": "gE-driven VZV reactivation damages sensory neurons, leading to chronic neuropathic pain.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "medium", "disease": "Herpes zoster ophthalmicus (HZO)", "glycan_involvement": "Glycosylation modulates gE\u2019s interaction with ocular tissues and immune cells.", "mechanism": "gE facilitates VZV spread to trigeminal nerve branches, causing ocular complications.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "medium", "disease": "Zoster sine herpete", "glycan_involvement": "Glycosylation may influence tissue tropism and subclinical spread.", "mechanism": "gE enables VZV reactivation in neurons without cutaneous involvement.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "medium", "disease": "VZV encephalitis", "glycan_involvement": "Glycosylation is critical for gE\u2019s neuroinvasive properties.", "mechanism": "gE mediates viral entry into CNS cells, leading to inflammation and encephalitis.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "medium", "disease": "VZV vasculopathy", "glycan_involvement": "Glycosylation affects gE\u2019s binding to endothelial cells and immune evasion.", "mechanism": "gE promotes VZV infection of vascular endothelial cells, causing vasculitis, thrombosis, and stroke.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "medium", "disease": "Ramsay-Hunt syndrome", "glycan_involvement": "Glycosylation modulates gE\u2019s neurotropism.", "mechanism": "gE enables VZV spread to facial nerve, causing palsy and rash.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "low", "disease": "Guillain-Barre syndrome (GBS)", "glycan_involvement": "Glycosylation may influence immune recognition and autoimmunity.", "mechanism": "gE-driven VZV reactivation may trigger autoimmune neuropathy.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "low", "disease": "Dementia/Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation may affect persistence and immune evasion in CNS.", "mechanism": "Chronic VZV infection via gE may contribute to neurodegeneration.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "low", "disease": "Progressive multifocal leukoencephalopathy", "glycan_involvement": "Glycosylation is important for CNS cell entry.", "mechanism": "gE mediates VZV infection of oligodendrocytes in immunocompromised hosts.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12125962" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding and cell surface expression.", "mechanism": "Targeted by ocrelizumab to deplete B cells, reducing inflammation and autoreactive T cells.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126224" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "CD16 glycosylation modulates Fc receptor function and immune signaling.", "mechanism": "Increased CD16+ monocytes after B cell depletion; associated with regulatory and TNF-\u03b1 producing phenotype.", "protein": "CD16 (FCGR3A)", "protein_enriched": { "function": "Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated", "gene_name": "FCGR3A", "glycan_count": 103, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02030ZB", "G05724UK", "G06110VR", "G08146BT", "G10773YW", "G11629QQ", "G11870QZ", "G20218ZS", "G21001NA", "G22310AV", "G22768VO", "G23294PN", "G23432EQ", "G23863VK", "G29880MM", "G32246SI", "G34617SM", "G34730YF", "G37442IW", "G37881RL", "G39188ZX", "G43947VZ", "G44215PV", "G44513XM", "G45495MK", "G45841FE", "G45889JQ", "G48390IG", "G55052CN", "G58232MG", "G61302NC", "G64394MX", "G64527OM", "G67381VP", "G68698AP", "G71569SN", "G72291OX", "G72667IM", "G72735IY", "G72797UR", "G74724QE", "G75983OB", "G80858MF", "G80966KZ", "G81263BG", "G82348BZ", "G82463GQ", "G83295QG", "G83624CJ", "G84452RH", "G84820NF", "G86795LJ", "G91636VS", "G14994KB", "G15169WU", "G91152KU", "G94854LT", "G16208YZ", "G28103WK", "G48488CO", "G57581QG", "G06356OH", "G10133VD", "G13728QT", "G16758MX", "G25418HZ", "G31153XO", "G37868ZX", "G42358LZ", "G48414YA", "G54982TL", "G59536GA", "G70101JE", "G72978AW", "G82830MN", "G93656SY", "G98719SR", "G69834CE", "G03382KH", "G17689DH", "G25520XG", "G26915XM", "G29011JC", "G31916IQ", "G31936TA", "G39213VZ", "G46687AB", "G49874UX", "G55220VL", "G60145BJ", "G62326NX", "G62389NM", "G63381RX", "G70418MS", "G72902CL", "G74430RZ", "G78059CC", "G82119TF", "G90093AU", "G90717TP", "G93141AZ", "G96095QD", "G96771UL" ], "uniprot_id": "P08637" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "CD14 is glycosylated, affecting LPS binding and immune activation.", "mechanism": "Post-treatment increase in CD14+ macrophages in CSF, associated with antiinflammatory phenotype.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "CD68 glycosylation influences lysosomal targeting and function.", "mechanism": "CD68+ macrophages in CSF increase after B cell depletion, linked to immune restoration.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126224" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MHC II glycosylation affects peptide presentation and T cell activation.", "mechanism": "HLA-DR-restricted autoreactive T cells drive MS; B cell depletion reduces myelin-reactive T cells.", "protein": "HLA-DR (MHC class II)", "protein_enriched": { "function": "An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting ", "gene_name": "HLA-DRA", "glycan_count": 88, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G04657PL", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G14972EH", "G27058EU", "G31852PQ", "G32788FZ", "G35541EV", "G37818NZ", "G39471UU", "G41247ZX", "G43223CG", "G43669FQ", "G45395BF", "G47644PP", "G47950XN", "G49642SA", "G50856PC", "G51653BI", "G53075ES", "G54740VA", "G55220VL", "G57776ZS", "G59324HL", "G60834IK", "G62765YT", "G65414LI", "G67164EE", "G68490OW", "G70101JE", "G70232NH", "G75568BH", "G76295SF", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G81637OR", "G86880BF", "G87123QX", "G90382BL", "G92275SC", "G93718GY", "G94156YI", "G95046LV", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G10773YW", "G11101UV", "G14669DU", "G15664MX", "G18647XP", "G22625SJ", "G22768VO", "G23984SE", "G25637MV", "G27947YN", "G28541PG", "G28681TP", "G37399XV", "G39188ZX", "G39446WN", "G40926MX", "G46503DX", "G49018RC", "G57776ZU", "G59626AS", "G59924QI", "G62894KT", "G64527OM", "G70619PT", "G72747WU", "G80920RR", "G82463GQ", "G83460ZZ", "G87661QW", "G89827JR", "G90659AW", "G92050GC", "G95865ZB" ], "uniprot_id": "P01903" }, "relationship_type": "causal", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "CD74 glycosylation modulates MHC II trafficking.", "mechanism": "Effector Tregs expressing HLA-DR and CD74 increase after B cell depletion, indicating regulatory shift.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "TIGIT is glycosylated, which may affect ligand binding and signaling.", "mechanism": "TIGIT+ Tregs expand after B cell depletion, promoting immune tolerance.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "protective", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "TNFR2 glycosylation influences receptor stability and signaling.", "mechanism": "Monocyte-derived TNF-\u03b1 may expand Tregs via TNFR2 signaling after B cell depletion.", "protein": "TNFR2 (TNFRSF1B)", "protein_enriched": { "function": "Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and", "gene_name": "TNFRSF1B", "glycan_count": 7, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G18717LR", "G45637XA", "G74722FL", "G81006GJ", "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "P20333" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126224" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MOG is a CNS glycoprotein; glycosylation may affect antigenicity.", "mechanism": "MOG is a target of autoreactive T cells; B cell depletion reduces MOG-reactive T cells.", "protein": "MOG (Myelin Oligodendrocyte Glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12126224" }, { "confidence": "medium", "disease": "Autoimmune Disorders", "glycan_involvement": "See above.", "mechanism": "B cell depletion via CD20 targeting is suggested as a strategy for other autoimmune diseases.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126224" }, { "confidence": "high", "disease": "Thyroid Dyshormonogenesis", "glycan_involvement": "Thyroglobulin is a glycoprotein; proper glycosylation is required for folding and secretion.", "mechanism": "Mutations in thyroglobulin gene (TG), such as p.Cys1476Arg, disrupt protein folding and dimerization, impairing thyroid hormone biosynthesis.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC12126254" }, { "confidence": "high", "disease": "Congenital Hypothyroidism", "glycan_involvement": "Glycosylation is essential for thyroglobulin stability and function.", "mechanism": "Defective thyroglobulin due to TG mutations leads to impaired thyroid hormone synthesis, resulting in hypothyroidism from birth.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC12126254" }, { "confidence": "high", "disease": "Goiter", "glycan_involvement": "Glycosylation defects may affect secretion and accumulation in the gland.", "mechanism": "Impaired thyroglobulin function causes compensatory thyroid enlargement due to elevated TSH.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC12126254" }, { "confidence": "medium", "disease": "Thyroid Nodules", "glycan_involvement": "Altered glycosylation may contribute to abnormal protein aggregation.", "mechanism": "Chronic TSH stimulation in TG-deficient states promotes nodule formation.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC12126254" }, { "confidence": "low", "disease": "Thyroid Cancer", "glycan_involvement": "Glycosylation status may influence protein stability and cellular stress.", "mechanism": "Long-term elevated TSH and nodular changes in TG mutation carriers may increase cancer risk.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "risk factor", "source_pmcid": "PMC12126254" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation is essential for stability and serum half-life.", "mechanism": "Serum transferrin levels reflect iron status; malignancy is associated with lower transferrin.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Serum LCN2 levels are lower in breast cancer patients compared to controls.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "high", "disease": "ER-negative breast cancer", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "Higher serum LCN2 levels are associated with ER-negative status, indicating aggressive disease.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "high", "disease": "PR-negative breast cancer", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Higher serum LCN2 levels correlate with PR-negative status.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "medium", "disease": "ER-negative breast cancer", "glycan_involvement": "Glycosylation may affect targeting and function.", "mechanism": "LCN2 may be a target for aggressive breast cancer subtypes due to its role in iron delivery.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126368" }, { "confidence": "medium", "disease": "PR-positive breast cancer", "glycan_involvement": "N-glycosylation required for serum stability.", "mechanism": "Transferrin levels are higher in PR-positive patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects stability and detection.", "mechanism": "High LCN2 levels are associated with poor prognosis and recurrence.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12126368" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for iron-binding and trafficking.", "mechanism": "LCN2 facilitates iron uptake in cancer cells, supporting proliferation.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "causal", "source_pmcid": "PMC12126368" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects receptor binding and clearance.", "mechanism": "Altered transferrin levels may be exploited for iron deprivation strategies.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126368" }, { "confidence": "medium", "disease": "ER-negative breast cancer", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "LCN2 upregulation in ER-negative tumors may result from cytokine-driven transcription.", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "causal", "source_pmcid": "PMC12126368" }, { "confidence": "high", "disease": "Distal Acquired Demyelinating Symmetric Neuropathy (DADS)", "glycan_involvement": "MAG is a glycoprotein; its glycosylation is essential for antibody recognition and pathogenicity.", "mechanism": "Anti-MAG antibodies target MAG, leading to distal demyelination and sensory-predominant neuropathy.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Antibody binding depends on glycosylated epitopes of MAG.", "mechanism": "High-titer anti-MAG antibodies serve as a diagnostic biomarker for anti-MAG neuropathy.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12126853" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "Immune response is directed against glycosylated MAG domains.", "mechanism": "Rituximab-induced immune modulation may trigger CIDP-like acute demyelination in anti-MAG patients.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 Syndrome (GBS)", "glycan_involvement": "Autoantibodies recognize glycosylated regions of MAG.", "mechanism": "Acute worsening after rituximab may mimic GBS due to immune attack on MAG.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "medium", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Therapeutic effect depends on reducing antibodies against glycosylated MAG.", "mechanism": "Rituximab targets B cells producing anti-MAG antibodies, aiming to reduce pathogenic antibody levels.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Glycosylation of MAG is required for antibody and complement binding.", "mechanism": "Colocalization of anti-MAG and complement C3d in myelin indicates antibody-mediated demyelination.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Antibody detection relies on glycosylated MAG epitopes.", "mechanism": "Stable or elevated anti-MAG antibody titers correlate with disease activity.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Glycosylation of MAG is critical for antibody binding and pathogenicity.", "mechanism": "Anti-MAG antibodies cause distal demyelination by binding to MAG on Schwann cells.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "medium", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Therapeutic response involves blocking antibody interaction with glycosylated MAG.", "mechanism": "Immunotherapies (IVIG, corticosteroids) can reverse rituximab-induced worsening by modulating anti-MAG antibody effects.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Anti-MAG Neuropathy", "glycan_involvement": "Glycosylation of MAG facilitates complement deposition and immune attack.", "mechanism": "Anti-MAG antibody-mediated complement activation leads to myelin damage.", "protein": "Myelin-Associated Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12126853" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is glycosylated, which may affect its stability and clearance.", "mechanism": "Elevated ferritin reflects macrophage activation and systemic inflammation in HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127017" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and bioactivity.", "mechanism": "IL-6 drives systemic inflammation and cytokine storm in HLH and babesiosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 contributes to macrophage activation and tissue injury in HLH.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "IL-1 glycosylation influences stability and immune signaling.", "mechanism": "IL-1 is a key mediator of fever and inflammation in HLH and babesiosis.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation is essential for perforin folding and function.", "mechanism": "Perforin deficiency impairs cytotoxic lymphocyte function, triggering HLH.", "protein": "Perforin", "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "CD8 glycosylation regulates cell-cell interactions and immune signaling.", "mechanism": "CD8+ T cell dysfunction leads to uncontrolled macrophage activation in HLH.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "CD56 glycosylation modulates receptor function and immune synapse formation.", "mechanism": "NK cell receptor dysfunction impairs cytotoxicity, promoting HLH.", "protein": "Natural Killer (NK) cell receptor (CD56)", "relationship_type": "causal", "source_pmcid": "PMC12127017" }, { "confidence": "medium", "disease": "Babesiosis", "glycan_involvement": "IgG glycosylation affects effector function and clearance.", "mechanism": "IgG response indicates Babesia infection and immune activation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127017" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Transferrin glycosylation influences iron binding and transport.", "mechanism": "Transferrin levels reflect iron metabolism disrupted in babesiosis-induced anemia.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127017" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Erythropoietin glycosylation is critical for stability and receptor activation.", "mechanism": "Erythropoietin stimulates erythropoiesis to counter anemia in babesiosis.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127017" }, { "confidence": "high", "disease": "Male infertility", "glycan_involvement": "Site-specific N/O-glycosylation at N128, S123, S130 modulates protein function.", "mechanism": "SPESP1 is essential for sperm fertilization ability; altered glycosylation may impair function.", "protein": "SPESP1 (Sperm Equatorial Segment Protein 1)", "protein_enriched": { "function": "Involved in fertilization ability of sperm", "gene_name": "SPESP1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q6UW49" }, "relationship_type": "causal", "source_pmcid": "PMC12127192" }, { "confidence": "high", "disease": "Impaired sperm motility", "glycan_involvement": "N/O-glycosylation at T39, S43, N249, N262, N338 affects activity and localization.", "mechanism": "SERPINA5 regulates sperm motility and protects sperm from protease-mediated damage.", "protein": "SERPINA5", "relationship_type": "causal", "source_pmcid": "PMC12127192" }, { "confidence": "high", "disease": "Proteolytic imbalance in semen", "glycan_involvement": "N/O-glycosylation modulates inhibitory function.", "mechanism": "Inhibits excessive acrosin release, preventing degradation of seminal proteins.", "protein": "SERPINA5", "relationship_type": "protective", "source_pmcid": "PMC12127192" }, { "confidence": "medium", "disease": "Immune-mediated infertility", "glycan_involvement": "N-glycosylation is critical for immune evasion.", "mechanism": "CD52 glycosylation protects sperm from immune attack in female tract.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "protective", "source_pmcid": "PMC12127192" }, { "confidence": "high", "disease": "Impaired fertilization", "glycan_involvement": "Glycan structure determines functional role in reproduction.", "mechanism": "Distinct glycoforms of glycodelin regulate fertilization processes.", "protein": "Glycodelin", "protein_enriched": { "function": "Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tiss", "gene_name": "PAEP", "glycan_count": 42, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G06110VR", "G06356OH", "G13290KJ", "G14696LD", "G23294PN", "G24835MQ", "G25837HW", "G27165KO", "G31916IQ", "G33671BL", "G33876UV", "G44339YF", "G46455GO", "G49874UX", "G51705EB", "G56749GV", "G66116BW", "G70418MS", "G72291OX", "G72667IM", "G75269BP", "G76012OT", "G76675AB", "G80858MF", "G81877PA", "G82463GQ", "G84452RH", "G86705PH", "G87889NL", "G92654OJ", "G93856AJ", "G02628JF", "G08110WX", "G22310AV", "G59821FL", "G60923RB", "G62765YT", "G81198YO", "G82592ZH", "G85228QD", "G87051GH", "G95977AE" ], "uniprot_id": "P09466" }, "relationship_type": "causal", "source_pmcid": "PMC12127192" }, { "confidence": "high", "disease": "Immune-mediated infertility", "glycan_involvement": "Fucosylation and sialylation mediate immune modulation.", "mechanism": "Specialized glycosylation patterns in SP promote immune tolerance.", "protein": "Seminal plasma glycoproteins (general)", "relationship_type": "protective", "source_pmcid": "PMC12127192" }, { "confidence": "medium", "disease": "Immune-mediated infertility", "glycan_involvement": "N-glycosylation affects IgG function.", "mechanism": "N-glycosylation of IgG in semen may modulate immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12127192" }, { "confidence": "low", "disease": "Male infertility", "glycan_involvement": "N/O-glycosylation impacts protein function.", "mechanism": "Glycosylation status may correlate with semen quality parameters.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127192" }, { "confidence": "low", "disease": "Male infertility", "glycan_involvement": "N/O-glycosylation modulates extracellular interactions.", "mechanism": "Altered glycosylation may affect sperm adhesion and motility.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127192" }, { "confidence": "medium", "disease": "Cancer (immunotherapy target)", "glycan_involvement": "N/O-glycosylation influences antigen presentation.", "mechanism": "SPESP1 is a testis-specific antigen; glycosylation may affect immunogenicity.", "protein": "SPESP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127192" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "HA is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "HA mediates viral entry into host cells and is the main antigenic target for neutralizing antibodies.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycosylation site changes alter antigenic sites and immune escape.", "mechanism": "HA sequence and antigenic properties are used to classify H1N1 clades and monitor antigenic drift.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127215" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycosylation modulates antibody accessibility to HA epitopes.", "mechanism": "HA is the primary target of influenza vaccines and neutralizing antibodies.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127215" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Substitutions at/near glycosylation sites alter glycan shield and antigenicity.", "mechanism": "HA antigenic drift (e.g., N156K, D187A, Q189E substitutions) enables immune escape and reduced vaccine effectiveness.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "N156 is a potential N-glycosylation site; mutation may alter glycan addition and antigenicity.", "mechanism": "N156K substitution in HA Sa antigenic site is associated with reduced antibody reactivity and increased circulation of 6B.1A.5a.2 clade.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "Located near glycosylation sites, potentially affecting glycan structure and immune recognition.", "mechanism": "D187A and Q189E substitutions in HA Sb antigenic site contribute to antigenic drift in 6B.1A.5a.1 clade.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "K130N creates a potential N-glycosylation site, possibly altering glycan shield.", "mechanism": "K130N substitution near Sa antigenic site in 6B.1A.5b and 6B.1A.5a.2 clades affects receptor binding and antigenicity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "K160 is part of a known glycosylation motif; mutation may disrupt glycan addition.", "mechanism": "K160M substitution in 6B.1A.5b clade affects Sa antigenic site and immune recognition.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "low", "disease": "Influenza A (H1N1)", "glycan_involvement": "Near glycosylation sites, may influence glycan structure.", "mechanism": "E235D substitution in Ca1 antigenic site in 6B.1A.5b clade affects antigenicity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127215" }, { "confidence": "medium", "disease": "Influenza B", "glycan_involvement": "Glycosylation status of HA influences cross-reactivity of antibodies.", "mechanism": "HA antibody titers used to distinguish immune response in IBV-infected vs. H1N1-infected individuals.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127215" }, { "confidence": "high", "disease": "Saint Louis encephalitis", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition", "mechanism": "Targeted by multi-epitope vaccine to induce immune response and protection", "protein": "membrane glycoprotein M", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127316" }, { "confidence": "high", "disease": "Saint Louis encephalitis", "glycan_involvement": "Glycosylation modulates immune evasion and epitope presentation", "mechanism": "Targeted by vaccine; contains immunodominant epitopes for B and T cell responses", "protein": "envelope protein E", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127316" }, { "confidence": "medium", "disease": "Saint Louis encephalitis", "glycan_involvement": "Not specified", "mechanism": "Included in vaccine design to broaden immune response", "protein": "anchored capsid protein anchC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127316" }, { "confidence": "medium", "disease": "West Nile virus infection", "glycan_involvement": "Glycosylation may influence cross-reactivity", "mechanism": "Conserved epitopes may induce cross-reactive T-cell responses", "protein": "envelope protein E", "relationship_type": "cross-protective", "source_pmcid": "PMC12127316" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation may influence cross-reactivity", "mechanism": "Conserved epitopes may induce cross-reactive T-cell responses", "protein": "envelope protein E", "relationship_type": "cross-protective", "source_pmcid": "PMC12127316" }, { "confidence": "low", "disease": "Dengue virus infection", "glycan_involvement": "Glycosylation may affect epitope similarity", "mechanism": "Some epitopes conserved; potential for cross-reactive immunity", "protein": "envelope protein E", "relationship_type": "cross-protective", "source_pmcid": "PMC12127316" }, { "confidence": "low", "disease": "Zika virus infection", "glycan_involvement": "Glycosylation may affect epitope similarity", "mechanism": "Some epitopes conserved; potential for cross-reactive immunity", "protein": "envelope protein E", "relationship_type": "cross-protective", "source_pmcid": "PMC12127316" }, { "confidence": "low", "disease": "Yellow fever", "glycan_involvement": "Glycosylation may affect epitope similarity", "mechanism": "Some sequence similarity; possible cross-reactivity", "protein": "envelope protein E", "relationship_type": "cross-protective", "source_pmcid": "PMC12127316" }, { "confidence": "high", "disease": "Saint Louis encephalitis", "glycan_involvement": "TLR4 glycosylation affects ligand binding and signaling", "mechanism": "Vaccine construct binds TLR4 to enhance innate immune activation", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127316" }, { "confidence": "medium", "disease": "Saint Louis encephalitis", "glycan_involvement": "Glycosylation may be required for proper folding and function", "mechanism": "Essential for viral assembly and infectivity", "protein": "membrane glycoprotein M", "relationship_type": "causal", "source_pmcid": "PMC12127316" }, { "confidence": "high", "disease": "Primary Open-Angle Glaucoma", "glycan_involvement": "Myocilin is a secreted glycoprotein; glycosylation may affect its secretion, folding, and aggregation, but specific glycan roles are not detailed in this article.", "mechanism": "Deleterious mutations in the C-terminal olfactomedin (OLF) domain of myocilin cause aggregation of misfolded proteins in the trabecular meshwork, obstructing aqueous humor outflow and increasing intraocular pressure.", "protein": "Myocilin", "protein_enriched": { "function": "Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organizatio", "gene_name": "MYOC", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99972" }, "relationship_type": "causal", "source_pmcid": "PMC12127701" }, { "confidence": "high", "disease": "Primary Open-Angle Glaucoma", "glycan_involvement": "No evidence that glycosylation at or near E414 is affected by this variant.", "mechanism": "The E414K substitution in the OLF domain does not significantly alter myocilin structure or function and is predicted to be benign.", "protein": "Myocilin (E414K variant)", "relationship_type": "neutral", "source_pmcid": "PMC12127701" }, { "confidence": "medium", "disease": "Primary Open-Angle Glaucoma", "glycan_involvement": "No direct evidence for glycan involvement at this site in this article.", "mechanism": "Mutations at aspartate-380 disrupt calcium binding, leading to misfolding and aggregation of myocilin, contributing to glaucoma.", "protein": "Myocilin (mutations at aspartate-380)", "relationship_type": "causal", "source_pmcid": "PMC12127701" }, { "confidence": "medium", "disease": "Primary Open-Angle Glaucoma", "glycan_involvement": "No direct evidence for glycan involvement at this site in this article.", "mechanism": "Mutations at aspartate-273 decrease thermal stability of myocilin, potentially leading to misfolding and aggregation.", "protein": "Myocilin (mutations at aspartate-273)", "relationship_type": "causal", "source_pmcid": "PMC12127701" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation affects ECM binding and stability.", "mechanism": "Upregulated in urinary extracellular vesicles of fibrotic kidneys; stabilizes PAI-1, inhibits fibrinolysis, promotes ECM accumulation.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation modulates interactions with ECM and PAI-1.", "mechanism": "Elevated in CKD and correlates with fibrosis severity.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect tissue localization.", "mechanism": "Upregulated in fibrotic liver tissue.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Lung fibrosis", "glycan_involvement": "Glycosylation may regulate ECM interactions.", "mechanism": "Elevated in fibrotic lungs.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Skin fibrosis", "glycan_involvement": "Glycosylation impacts ECM binding.", "mechanism": "Upregulated in fibrotic skin.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127770" }, { "confidence": "low", "disease": "Neurodegenerative conditions", "glycan_involvement": "Glycosylation may affect tissue distribution.", "mechanism": "Elevated in degenerative nervous system conditions.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127770" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Upregulated in urine and uEV; recruits monocytes/macrophages, activates pro-fibrotic pathways.", "protein": "MCP-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127770" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation affects inhibitory activity and stability.", "mechanism": "Inhibits fibrinolysis, promotes ECM accumulation; stabilized by vitronectin.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation required for cell surface localization.", "mechanism": "Upregulated in fibrotic kidneys; regulates plasminogen activation and ECM remodeling.", "protein": "uPAR", "relationship_type": "causal", "source_pmcid": "PMC12127770" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "Upregulated in fibrotic kidneys; mediates TNF signaling, inflammation, and fibrosis progression.", "protein": "TNFR1/TNFR2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127770" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Altered glycosylation affects insulin receptor signaling.", "mechanism": "Insulin resistance and impaired glycosylation contribute to T2D pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12127887" }, { "confidence": "high", "disease": "Coronary Heart Disease", "glycan_involvement": "Glycosylation modulates receptor function and drug efficacy.", "mechanism": "GLP-1 receptor agonists reduce cardiovascular risk in T2D.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127887" }, { "confidence": "high", "disease": "Coronary Heart Disease", "glycan_involvement": "Glycosylation affects SGLT2 stability and membrane localization.", "mechanism": "SGLT2 inhibitors lower CVD risk in T2D.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127887" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation is critical for LDL receptor function.", "mechanism": "LDL receptor dysfunction leads to lipid accumulation and atherosclerosis.", "protein": "LDL receptor", "relationship_type": "causal", "source_pmcid": "PMC12127887" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycans regulate ICAM-1-mediated cell adhesion.", "mechanism": "Elevated ICAM-1 promotes leukocyte adhesion and vascular inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates VCAM-1 binding affinity.", "mechanism": "VCAM-1 mediates monocyte adhesion to endothelium in atherosclerosis.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127887" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Sialylated glycans are essential for E-selectin ligand recognition.", "mechanism": "E-selectin facilitates leukocyte recruitment during acute MI.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127887" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation influences ApoB100 secretion and function.", "mechanism": "ApoB100 is required for VLDL/LDL assembly; its glycosylation affects lipid metabolism.", "protein": "ApoB100", "protein_enriched": { "function": "Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalizati", "gene_name": "APOB", "glycan_count": 140, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G49108TO", "G00912UN", "G06356OH", "G08918WF", "G10486CT", "G22140GZ", "G28622IK", "G31916IQ", "G37399XV", "G37868ZX", "G40574BA", "G42358LZ", "G45504EY", "G48414YA", "G50045TK", "G59626AS", "G72291OX", "G75983OB", "G81295CK", "G82463GQ", "G95865ZB", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15169WU", "G15664MX", "G17208MA", "G23719VF", "G31852PQ", "G47518TP", "G52527GH", "G59536GA", "G60667HJ", "G62765YT", "G64527OM", "G70101JE", "G70888PK", "G72747WU", "G76295SF", "G80920RR", "G81124ET", "G82830MN", "G85554PZ", "G90659AW", "G42962KI", "G44215PV", "G47644PP", "G86182NS", "G10846ZT", "G11911BT", "G26330YA", "G27915IV", "G37881RL", "G45395BF", "G47737VJ", "G85269DF", "G57321FI", "G01650EU", "G27058EU", "G27126ED", "G28681TP", "G57776ZU", "G70619PT", "G94470IW", "G43417UB", "G39188ZX", "G41247ZX", "G50282JC", "G63980BQ", "G65363KE", "G77547TA", "G88891KO", "G90575OW", "G90734RJ", "G98129XB", "G06247RL", "G08293MJ", "G11629QQ", "G22310AV", "G23294PN", "G23453IV", "G27947YN", "G33609NS", "G39446WN", "G39595FH", "G40926MX", "G42124LM", "G55220VL", "G55412XP", "G61256FT", "G69834CE", "G71560PC", "G72787SB", "G84452RH", "G88374WZ", "G00273SJ", "G41840AI", "G48584BU", "G03644CB", "G04854VP", "G14547CB", "G31986NC", "G37692EO", "G57776ZS", "G60033FS", "G70232NH", "G72790NZ", "G80075MS", "G80505LH", "G86880BF", "G89098OM", "G92551JA", "G94917XT", "G99668VU", "G56784JY", "G78790NZ", "G04689DA", "G10073SM", "G15956KF", "G22340YC", "G28839WC", "G34449FW", "G36598FV", "G37020YV", "G37369XO", "G44306ED", "G49447IS", "G61151LQ", "G62785VB", "G67381VP", "G72735IY", "G76014WR", "G77852EK", "G79167DN", "G79982IL", "G80123ZU", "G88509SO", "G97101NC", "G98719SR" ], "uniprot_id": "P04114" }, "relationship_type": "causal", "source_pmcid": "PMC12127887" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Increased sialylation in T2D.", "mechanism": "Altered transferrin glycoforms reflect chronic hyperglycemia.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127887" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycosylation modulates fibrinogen clot properties.", "mechanism": "Hyperfibrinogenemia increases thrombosis risk in stroke.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12127887" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Fas is N-glycosylated, which affects receptor stability and ligand binding.", "mechanism": "Upregulation of Fas receptor on CD4+ T-cells and monocytes promotes apoptosis and cell depletion.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12128504" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "FasL glycosylation modulates its membrane localization and apoptotic activity.", "mechanism": "Increased FasL expression on immune cells induces apoptosis of uninfected bystander CD4+ T-cells.", "protein": "Fas Ligand (FasL)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-m", "gene_name": "FASLG", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48023" }, "relationship_type": "causal", "source_pmcid": "PMC12128504" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "TRAIL is glycosylated, influencing receptor interaction and apoptotic signaling.", "mechanism": "TRAIL induces apoptosis in infected and uninfected CD4+ T-cells and monocytes, contributing to cell depletion.", "protein": "TRAIL (TNFSF10)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (PubMed:10549288, PubMed:26457518). Induces apoptosis. Its activity", "gene_name": "TNFSF10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P50591" }, "relationship_type": "causal", "source_pmcid": "PMC12128504" }, { "confidence": "high", "disease": "HIV disease progression", "glycan_involvement": "DR5 N-glycosylation affects receptor surface expression and ligand binding.", "mechanism": "DR5 expression is significantly increased in CD4+ T-cells and monocytes from PLWHIV, correlates positively with infection time and IL-18 levels.", "protein": "DR5 (TRAIL-R2)", "protein_enriched": { "function": "Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:10549288). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) perform", "gene_name": "TNFRSF10B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "O14763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128504" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation may influence antibody binding and receptor function.", "mechanism": "Blockade of DR5 reduces apoptosis of CD4+ T-cells, suggesting potential for therapeutic intervention.", "protein": "DR5 (TRAIL-R2)", "protein_enriched": { "function": "Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:10549288). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) perform", "gene_name": "TNFRSF10B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "O14763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128504" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "CXCR4 glycosylation modulates HIV gp120 binding and receptor signaling.", "mechanism": "CXCR4 expression correlates with DR5 upregulation, facilitating TRAIL-mediated apoptosis and rapid CD4+ T-cell depletion in late-stage HIV.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC12128504" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "CCR5 glycosylation affects HIV entry and coreceptor function.", "mechanism": "CCR5 expression decreases with disease progression, reflecting loss of CCR5+ cells due to HIV tropism shift.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal", "source_pmcid": "PMC12128504" }, { "confidence": "medium", "disease": "HIV disease progression", "glycan_involvement": "CD38 glycosylation influences enzymatic activity and cell surface expression.", "mechanism": "CD38 upregulation on CD4+ T-cells is associated with immune activation and poor prognosis in PLWHIV.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128504" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "CD80 glycosylation modulates costimulatory function.", "mechanism": "CD80 expression may regulate pro-apoptotic and anti-apoptotic molecule expression, impacting cell survival in advanced HIV.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "protective", "source_pmcid": "PMC12128504" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "CD86 glycosylation affects ligand binding and immune signaling.", "mechanism": "CD86 stimulation improves macrophage viability and may regulate apoptosis in immune cells.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "protective", "source_pmcid": "PMC12128504" }, { "confidence": "high", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "CD22 is a sialic acid-binding glycoprotein; glycosylation modulates ligand binding and cell signaling.", "mechanism": "Aberrant expression of CD22 on neoplastic plasma cells suggests a transitional immunophenotypic stage between immunoblasts and mature plasma cells.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "high", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "Heparan sulfate glycosylation is essential for cell adhesion and tumor microenvironment interactions.", "mechanism": "CD138 marks plasma cell lineage and is consistently expressed in neoplastic plasma cells.", "protein": "CD138", "protein_enriched": { "function": "May act as a modulatory subunit rather than a functional channel. Unlike other P2XRs members, P2RX6 does not seem to form functional homotrimers (PubMed:22378790). P2RX6 requires the presence of P2RX4", "gene_name": "P2RX6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O15547" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "high", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "N-glycosylation affects CD38 stability and ligand interactions.", "mechanism": "CD38 is highly expressed on plasma cells and used for diagnostic flow cytometry.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "medium", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "Glycosylation modulates receptor-ligand binding.", "mechanism": "CD27 expression is variable in plasma cell neoplasms and may indicate maturation stage.", "protein": "CD27", "protein_enriched": { "function": "Costimulatory immune-checkpoint receptor expressed at the surface of T-cells, NK-cells and B-cells which binds to and is activated by its ligand CD70/CD27L expressed by B-cells (PubMed:28011863). The ", "gene_name": "CD27", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G22310AV", "G64275UO", "G91473PK" ], "uniprot_id": "P26842" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "medium", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "Glycosylation affects membrane localization and protein interactions.", "mechanism": "CD81 is variably expressed and may influence cell signaling and adhesion.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "medium", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "Glycosylation required for LPS binding and immune signaling.", "mechanism": "Aberrant expression of CD14 (normally monocytic marker) in plasma cell neoplasms indicates immunophenotypic abnormality.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "medium", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Sialic acid-dependent glycosylation modulates B cell receptor signaling.", "mechanism": "CD22 is typically absent in mature plasma cells; its presence may indicate atypical differentiation.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Heparan sulfate chains mediate cell adhesion and growth factor binding.", "mechanism": "CD138 is a standard marker for MM diagnosis and plasma cell identification.", "protein": "CD138", "protein_enriched": { "function": "May act as a modulatory subunit rather than a functional channel. Unlike other P2XRs members, P2RX6 does not seem to form functional homotrimers (PubMed:22378790). P2RX6 requires the presence of P2RX4", "gene_name": "P2RX6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O15547" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128895" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Glycosylation influences antibody binding and immune clearance.", "mechanism": "CD38 is targeted by monoclonal antibodies in MM therapy.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128895" }, { "confidence": "medium", "disease": "Plasma Cell Leukemia (PCL)", "glycan_involvement": "Glycosylation affects antibody targeting and receptor function.", "mechanism": "CD22 may represent a novel therapeutic target in PCL due to its unexpected expression.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128895" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation critical for viral infectivity and immune modulation.", "mechanism": "Viral glycoproteins mediate host cell entry and immune evasion, causing CCHF.", "protein": "Nairovirus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12129135" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Altered glycosylation may affect platelet survival and clearance.", "mechanism": "Platelet glycoprotein loss or dysfunction contributes to low platelet count in CCHF.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12129135" }, { "confidence": "medium", "disease": "Viral myocarditis", "glycan_involvement": "Glycosylation status may influence susceptibility to viral damage.", "mechanism": "Direct viral infiltration may damage myocardial glycoproteins, impairing conduction.", "protein": "Myocardial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12129135" }, { "confidence": "medium", "disease": "Bradycardia", "glycan_involvement": "Glycosylation may modulate viral tropism for cardiac tissue.", "mechanism": "Viral glycoprotein-mediated myocarditis may disrupt cardiac conduction, leading to bradycardia.", "protein": "Nairovirus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12129135" }, { "confidence": "medium", "disease": "Crimean-Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycan modifications may affect platelet function in CCHF.", "mechanism": "Platelet glycoprotein levels reflect disease severity and hemorrhagic risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12129135" }, { "confidence": "high", "disease": "Root caries (RC)", "glycan_involvement": "Heavily O-glycosylated extracellular domain mediates interactions with bacteria and other mucins.", "mechanism": "Elevated salivary MUC1 levels are associated with increased susceptibility to root caries; MUC1 may act as a scaffold for secreted mucins, influencing bacterial colonization and caries risk.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12129288" }, { "confidence": "high", "disease": "Root caries (RC)", "glycan_involvement": "Glycosylation may affect albumin's stability and diffusion into saliva.", "mechanism": "Lower salivary albumin levels are associated with higher RC risk; albumin inhibits enamel demineralization by blocking surface pores.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12129288" }, { "confidence": "medium", "disease": "Root caries (RC)", "glycan_involvement": "Glycosylation of IgA is essential for its stability and immune function in saliva.", "mechanism": "Higher salivary globulin (mainly IgA) levels observed in RC, reflecting immune response to caries progression.", "protein": "Globulin (Immunoglobulins)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12129288" }, { "confidence": "low", "disease": "Root caries (RC)", "glycan_involvement": "N-glycosylation affects enzyme activity and bacterial binding.", "mechanism": "No significant difference in amylase levels between RC and non-RC, but literature suggests amylase may promote biofilm formation and starch hydrolysis, contributing to caries.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12129288" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "O-glycosylation modulates bacterial adhesion and mucin-mucin interactions.", "mechanism": "Higher MUC1 levels correlate with higher DMF (decayed, missing, filled) scores; increased MUC1 shedding may exacerbate caries susceptibility.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12129288" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Extensive O-glycosylation forms gel-like protective barriers.", "mechanism": "Elevated MUC5B concentration and interaction with MUC1 may increase caries susceptibility by altering mucosal barrier and bacterial colonization.", "protein": "Mucin-5B (MUC5B)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12129288" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "O-glycosylation mediates microbial interactions.", "mechanism": "MUC7 contributes to oral lubrication and microbial binding, potentially reducing caries risk.", "protein": "Mucin-7 (MUC7)", "protein_enriched": { "function": "Chemotactic activity for lymphocytes but not for monocytes or neutrophils", "gene_name": "XCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBD3" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12129288" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Glycosylation may influence albumin's oral bioavailability.", "mechanism": "Low salivary albumin is associated with increased caries risk; albumin may inhibit demineralization.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12129288" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Glycosylation critical for IgA function.", "mechanism": "Elevated salivary IgA levels reflect immune response to caries; may help limit progression.", "protein": "Globulin (Immunoglobulins)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12129288" }, { "confidence": "low", "disease": "Root caries (RC)", "glycan_involvement": "Includes multiple glycoproteins with diverse glycosylation patterns.", "mechanism": "No significant difference in total protein between RC and non-RC; total protein may have both protective and harmful effects depending on composition.", "protein": "Total salivary protein", "relationship_type": "biomarker", "source_pmcid": "PMC12129288" }, { "confidence": "high", "disease": "Medullary Thyroid Carcinoma (MTC)", "glycan_involvement": "Calcitonin is derived from a glycoprotein precursor; glycosylation may affect stability.", "mechanism": "Elevated serum calcitonin is a sensitive marker for MTC due to C cell proliferation.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Pulmonary Neuroendocrine Tumor (NET)", "glycan_involvement": "Glycosylation may influence secretion and detection.", "mechanism": "Ectopic secretion of calcitonin by pulmonary NETs leads to elevated serum levels.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Pulmonary Neuroendocrine Tumor (NET)", "glycan_involvement": "CD56 is a glycoprotein; glycosylation affects cell adhesion and tumor cell interactions.", "mechanism": "CD56 is highly expressed in NETs, aiding diagnosis.", "protein": "CD56 (Neural Cell Adhesion Molecule-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Pulmonary Neuroendocrine Tumor (NET)", "glycan_involvement": "Glycosylation impacts secretion and immunoreactivity.", "mechanism": "Chromogranin A is stored in neuroendocrine granules and is a diagnostic marker for NETs.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Pulmonary Neuroendocrine Tumor (NET)", "glycan_involvement": "Glycosylation modulates membrane localization and detection.", "mechanism": "Synaptophysin is a synaptic vesicle glycoprotein expressed in NETs.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "medium", "disease": "Medullary Thyroid Carcinoma (MTC)", "glycan_involvement": "CEA is heavily glycosylated; glycan structures affect antigenicity.", "mechanism": "CEA is often positive in MTC, supporting diagnosis.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Small Cell Lung Carcinoma", "glycan_involvement": "Glycosylation modulates cell adhesion and tumor spread.", "mechanism": "CD56 is expressed in small cell lung carcinoma, aiding in diagnosis.", "protein": "CD56 (Neural Cell Adhesion Molecule-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Atypical Carcinoid Tumor", "glycan_involvement": "Glycosylation may affect hormone processing and release.", "mechanism": "Atypical carcinoid tumors can ectopically secrete calcitonin, causing elevated serum levels.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "medium", "disease": "Pheochromocytoma", "glycan_involvement": "Glycosylation affects stability and detection.", "mechanism": "Chromogranin A is elevated in pheochromocytoma due to neuroendocrine origin.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "medium", "disease": "Gastric Carcinoid", "glycan_involvement": "Glycosylation may influence secretion.", "mechanism": "Gastric carcinoids may secrete calcitonin, leading to elevated serum levels.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129487" }, { "confidence": "high", "disease": "Diverticular disease (DD)", "glycan_involvement": "CD5 is a heavily glycosylated cell surface protein; glycosylation may affect T-cell activation and signaling", "mechanism": "Higher CD5 levels increase DD risk, partially mediated by gut microbiome changes (g_Bilophila, inosine 5\u2019-phosphate biosynthesis I pathway)", "protein": "T-cell surface glycoprotein CD5", "protein_enriched": { "function": "Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differe", "gene_name": "CD5", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU", "G23863VK", "G51519NL", "G63889NK", "G72797UR", "G78059CC", "G80218BM", "G86357DX", "G90093AU" ], "uniprot_id": "P06127" }, "relationship_type": "causal", "source_pmcid": "PMC12129536" }, { "confidence": "medium", "disease": "Diverticular disease (DD)", "glycan_involvement": "Glycosylation modulates CD5 function and cell-cell interactions", "mechanism": "CD5-mediated T-cell activation may drive inflammation in DD", "protein": "T-cell surface glycoprotein CD5", "protein_enriched": { "function": "Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differe", "gene_name": "CD5", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU", "G23863VK", "G51519NL", "G63889NK", "G72797UR", "G78059CC", "G80218BM", "G86357DX", "G90093AU" ], "uniprot_id": "P06127" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129536" }, { "confidence": "medium", "disease": "Diverticular disease (DD)", "glycan_involvement": "IL-10 is glycosylated; glycosylation affects secretion and stability", "mechanism": "Genetically higher IL-10 levels associated with increased DD risk", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "causal", "source_pmcid": "PMC12129536" }, { "confidence": "medium", "disease": "Diverticular disease (DD)", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and bioactivity", "mechanism": "Higher IL-6 levels genetically associated with reduced DD risk", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "protective", "source_pmcid": "PMC12129536" }, { "confidence": "medium", "disease": "Diverticular disease (DD)", "glycan_involvement": "Eotaxin is glycosylated; glycosylation may affect chemokine gradient formation", "mechanism": "Higher eotaxin levels genetically associated with reduced DD risk", "protein": "Eotaxin (CCL11)", "protein_enriched": { "function": "In response to the presence of allergens, this protein directly promotes the accumulation of eosinophils, a prominent feature of allergic inflammatory reactions (PubMed:8597956). Binds to CCR3 (PubMed", "gene_name": "CCL11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51671" }, "relationship_type": "protective", "source_pmcid": "PMC12129536" }, { "confidence": "low", "disease": "Diverticular disease (DD)", "glycan_involvement": "CUB domain proteins are often glycosylated, affecting secretion and interactions", "mechanism": "Genetically higher levels associated with increased DD risk", "protein": "CUB domain-containing protein 1", "protein_enriched": { "function": "Mediates apoptosis and actin stress fiber dissolution", "gene_name": "SLK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2G2" }, "relationship_type": "causal", "source_pmcid": "PMC12129536" }, { "confidence": "low", "disease": "Diverticular disease (DD)", "glycan_involvement": "GDNF glycosylation affects stability and receptor binding", "mechanism": "Higher GDNF levels genetically associated with reduced DD risk", "protein": "Glial cell line-derived neurotrophic factor (GDNF)", "protein_enriched": { "function": "Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake (PubMed:8493557). Acts by binding to its corecept", "gene_name": "GDNF", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P39905" }, "relationship_type": "protective", "source_pmcid": "PMC12129536" }, { "confidence": "high", "disease": "Diverticular disease (DD)", "glycan_involvement": "Glycosylation of CD5 may influence T-cell\u2013microbiome interactions", "mechanism": "23.96% of CD5 effect on DD is mediated by increased g_Bilophila abundance", "protein": "T-cell surface glycoprotein CD5", "protein_enriched": { "function": "Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differe", "gene_name": "CD5", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU", "G23863VK", "G51519NL", "G63889NK", "G72797UR", "G78059CC", "G80218BM", "G86357DX", "G90093AU" ], "uniprot_id": "P06127" }, "relationship_type": "causal (mediated)", "source_pmcid": "PMC12129536" }, { "confidence": "high", "disease": "Diverticular disease (DD)", "glycan_involvement": "Glycosylation may modulate CD5 signaling affecting microbial metabolism", "mechanism": "24.63% of CD5 effect on DD is mediated by decreased activity of inosine 5\u2019-phosphate biosynthesis I pathway", "protein": "T-cell surface glycoprotein CD5", "protein_enriched": { "function": "Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differe", "gene_name": "CD5", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU", "G23863VK", "G51519NL", "G63889NK", "G72797UR", "G78059CC", "G80218BM", "G86357DX", "G90093AU" ], "uniprot_id": "P06127" }, "relationship_type": "causal (mediated)", "source_pmcid": "PMC12129536" }, { "confidence": "medium", "disease": "Diverticular disease (DD)", "glycan_involvement": "Glycosylation state may influence detection and function as biomarker", "mechanism": "CD5 levels reflect T-cell activation status in DD pathogenesis", "protein": "T-cell surface glycoprotein CD5", "protein_enriched": { "function": "Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differe", "gene_name": "CD5", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU", "G23863VK", "G51519NL", "G63889NK", "G72797UR", "G78059CC", "G80218BM", "G86357DX", "G90093AU" ], "uniprot_id": "P06127" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129536" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike glycoprotein mediates viral entry into host cells by binding to host receptors and facilitating membrane fusion.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12129616" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity, influencing vaccine design.", "mechanism": "Spike glycoprotein is the primary antigenic target for vaccine development, including subunit and epitope-based vaccines.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129616" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation can affect detection sensitivity in serological assays.", "mechanism": "Presence of spike glycoprotein or anti-spike antibodies is used for diagnosis and immune response monitoring.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12129616" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shielding may limit but does not prevent protective immune responses.", "mechanism": "Induction of neutralizing antibodies and CTL responses against spike glycoprotein confers protection.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12129616" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Epitope selection considers glycan shielding to enhance immune accessibility.", "mechanism": "CTL epitopes derived from spike glycoprotein are used in subunit vaccine constructs to elicit cytotoxic T cell responses.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129616" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect epitope exposure and antibody binding.", "mechanism": "Autoantibodies target conformational epitopes on MOG, triggering complement activation, ADCC, and demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12129762" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation may influence antigenicity and antibody recognition.", "mechanism": "Serum MOG-IgG is diagnostic and correlates with disease activity and relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129762" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Targeted by rituximab to deplete B cells, reducing MOG-IgG production.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "FcRn is a glycoprotein; glycosylation may modulate IgG binding.", "mechanism": "Inhibition by rozanolixizumab accelerates IgG degradation, lowering pathogenic MOG-IgG.", "protein": "Neonatal Fc receptor (FcRn)", "protein_enriched": { "function": "Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degrad", "gene_name": "DET1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7L5Y6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "IL-6R is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Blocked by tocilizumab/satralizumab to inhibit IL-6 signaling, reducing inflammation and relapses.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "C1q is a glycoprotein; glycosylation may influence complement activation.", "mechanism": "Binds MOG-IgG complexes, activating classical complement pathway and mediating CDC.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Heavily glycosylated; glycosaminoglycan chains may modulate cell interactions.", "mechanism": "Expressed on plasma cells producing MOG-IgG in lesions.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may affect cell surface expression.", "mechanism": "Marks plasmablasts/plasma cells involved in MOG-IgG production.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129762" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "C3d is a glycoprotein fragment; glycosylation may affect immune complex formation.", "mechanism": "MOG can bind C3d, amplifying complement activation and demyelination.", "protein": "C3d", "relationship_type": "causal", "source_pmcid": "PMC12129762" }, { "confidence": "low", "disease": "MOGAD", "glycan_involvement": "CD19 is a glycoprotein; glycosylation may influence antibody targeting.", "mechanism": "Expressed on B cells; potential target for B cell depletion therapies.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129762" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "N-glycosylation shields gp120 from immune recognition and facilitates immune evasion.", "mechanism": "gp120 mediates viral entry by binding to CD4 and co-receptors on host cells.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "causal", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycan shield (e.g., N332 glycan shift) modulates antibody accessibility.", "mechanism": "gp120 epitopes are targeted in vaccine design to elicit neutralizing antibodies.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation site mutations correlate with immune escape.", "mechanism": "gp120 sequence variability and glycosylation patterns are used to subtype HIV and monitor immune escape.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "AIDS", "glycan_involvement": "Glycan shield contributes to chronic infection and immune exhaustion.", "mechanism": "Persistent gp120-mediated infection leads to CD4+ T cell depletion and AIDS progression.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "causal", "source_pmcid": "PMC12129944" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Epitope selection considers glycan variability to enhance vaccine efficacy.", "mechanism": "Vaccine-induced antibodies targeting gp120 can neutralize HIV and prevent infection.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "protective", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Protease is essential for viral maturation and is targeted by antiretroviral drugs.", "protein": "Protease", "protein_enriched": { "function": "Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruit", "gene_name": "gag-pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q75002" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Reverse transcriptase is required for viral replication and is targeted by antiretroviral drugs.", "protein": "Reverse transcriptase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Integrase mediates integration of viral DNA into host genome; targeted by antiretroviral drugs.", "protein": "Integrase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Altered N-glycosylation at N332 site changes antibody binding.", "mechanism": "N332 glycan shift mutation enables escape from broadly neutralizing antibodies.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "immune escape", "source_pmcid": "PMC12129944" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Vaccine design includes mutated glycosylation sites to broaden immune response.", "mechanism": "Epitope-based vaccines incorporating glycan variability aim to overcome strain-specific immune evasion.", "protein": "Envelope glycoprotein (gp120)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 25, "glytoucan_ids": [], "uniprot_id": "Q75008" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129944" }, { "confidence": "high", "disease": "Choledocholithiasis", "glycan_involvement": "GGT is a glycosylated membrane protein; glycosylation affects its stability and localization.", "mechanism": "Elevated GGT indicates cholestasis and bile duct obstruction due to stones.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "high", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation modulates enzyme activity and secretion.", "mechanism": "Elevated levels reflect biliary obstruction.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "Elevated AST signals hepatocellular injury secondary to gallstones.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation influences enzyme half-life.", "mechanism": "ALT elevation indicates liver injury due to gallstones.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "high", "disease": "Pigment gallstones", "glycan_involvement": "Albumin glycosylation affects bilirubin binding and transport.", "mechanism": "Unconjugated bilirubin precipitates as calcium bilirubinate, forming pigment stones.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "causal", "source_pmcid": "PMC12130344" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "CCK-1 receptor mutations/deletions impair gallbladder contractility, increasing stone risk.", "protein": "Cholecystokinin receptor (CCK-1)", "protein_enriched": { "function": "Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastri", "gene_name": "CCKAR", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P32238" }, "relationship_type": "causal", "source_pmcid": "PMC12130344" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation required for FGF19 secretion and activity.", "mechanism": "Excessive FGF19 release impairs gallbladder function, promoting stone formation.", "protein": "Fibroblast growth factor 19 (FGF19)", "protein_enriched": { "function": "Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocyte", "gene_name": "FGF19", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95750" }, "relationship_type": "causal", "source_pmcid": "PMC12130344" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation affects enzyme folding and activity.", "mechanism": "CYP7A1 mutations disrupt bile acid synthesis, increasing cholesterol stone risk.", "protein": "Cholesterol 7-alpha hydroxylase (CYP7A1)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) (PubMed:11013305, PubMed:12077124, PubMed:19965590, PubMed:21813643, Pu", "gene_name": "CYP7A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22680" }, "relationship_type": "causal", "source_pmcid": "PMC12130344" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation essential for membrane localization.", "mechanism": "GGT elevation is a sensitive marker of cholestasis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation regulates enzyme secretion.", "mechanism": "Alkaline phosphatase increases in cholestatic liver disease.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130344" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation of CD98hc is required for Gal-8 binding and downstream signaling.", "mechanism": "CD98hc overexpression promotes malignant transformation and progression; Gal-8 binding may regulate amino acid transport and integrin signaling.", "protein": "CD98hc", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130729" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Binds N-glycosylated CD98hc and other glycoproteins.", "mechanism": "Gal-8 modulates cell adhesion, migration, and apoptosis via glycoprotein interactions, influencing tumor progression.", "protein": "Galectin-8", "relationship_type": "biomarker", "source_pmcid": "PMC12130729" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation mediates Gal-8 binding.", "mechanism": "CD44vRA-Gal-8 complex formation influences autoimmune inflammatory response.", "protein": "CD44vRA", "relationship_type": "causal", "source_pmcid": "PMC12130729" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation-dependent Gal-8 binding.", "mechanism": "CD166-Gal-8 interaction regulates cell adhesion, migration, and angiogenesis, correlating with poor prognosis.", "protein": "CD166 (ALCAM)", "protein_enriched": { "function": "Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:15048703, PubMed:15496415, PubMed:16352806, PubMe", "gene_name": "ALCAM", "glycan_count": 163, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G02815KT", "G04657PL", "G05049YU", "G06110VR", "G06356OH", "G07755XJ", "G08918WF", "G10486CT", "G14972EH", "G17208MA", "G20210JR", "G23863VK", "G25451PN", "G27058EU", "G27126ED", "G34989PA", "G37412TK", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G46503DX", "G46691LC", "G47012YE", "G48414YA", "G49018RC", "G50045TK", "G58954YZ", "G59626AS", "G60033FS", "G60177UT", "G60923RB", "G65184UU", "G70101JE", "G70619PT", "G72790NZ", "G75983OB", "G76295SF", "G79666IR", "G80223IX", "G83229XP", "G83646BJ", "G84452RH", "G84820NF", "G86182NS", "G87051GH", "G87661QW", "G90659AW", "G90734RJ", "G92062TF", "G95133RI", "G95177YH", "G95865ZB", "G01160VV", "G05962QB", "G06247RL", "G07246CJ", "G10819WX", "G11115RO", "G13131HA", "G16125XL", "G18183SM", "G22589VJ", "G27915IV", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G34617SM", "G35541EV", "G38663NM", "G43089EG", "G50427EO", "G52890YB", "G53075ES", "G55132BD", "G57776ZS", "G62765YT", "G64394MX", "G68490OW", "G70232NH", "G70441OD", "G70894RY", "G72797UR", "G79286RS", "G80479JV", "G80920RR", "G81263BG", "G85282JO", "G85554PZ", "G87123QX", "G90093AU", "G90382BL", "G92135MA", "G93718GY", "G96577RX", "G98611JV", "G02030ZB", "G11629QQ", "G11870QZ", "G20312EM", "G25418HZ", "G31544HA", "G33791AF", "G43734MM", "G47644PP", "G51640FO", "G64527OM", "G66163OV", "G69521XL", "G77547TA", "G77582RK", "G80075MS", "G82830MN", "G84225JN", "G86795LJ", "G05933EN", "G08290VR", "G15169WU", "G18647XP", "G23294PN", "G37881RL", "G40834TG", "G47518TP", "G63041LO", "G66760KM", "G78649WQ", "G96430BV", "G02852RP", "G00273SJ", "G05724UK", "G10773YW", "G10846ZT", "G12313PD", "G13749ZZ", "G14260UH", "G23984SE", "G31852PQ", "G37399XV", "G39188ZX", "G40926MX", "G41126SR", "G41840AI", "G44753VC", "G49906RN", "G50372IH", "G62894KT", "G70418MS", "G72291OX", "G72735IY", "G82463GQ", "G86880BF", "G54992WG", "G65414LI", "G83676GD", "G52527GH", "G63381RX", "G70822IO", "G49108TO" ], "uniprot_id": "Q13740" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130729" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "O-glycosylation of PDPN required for Gal-8 binding.", "mechanism": "Gal-8-PDPN interaction promotes lymphangiogenesis and cancer cell migration.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "causal", "source_pmcid": "PMC12130729" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation-dependent Gal-8 binding.", "mechanism": "Gal-8 binding to CD45 activates T cells, potentially impacting autoimmune disease progression.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "causal", "source_pmcid": "PMC12130729" }, { "confidence": "medium", "disease": "Platelet dysfunction", "glycan_involvement": "Carbohydrate-dependent Gal-8 binding.", "mechanism": "Gal-8-FV interaction mediates FV endocytosis, regulating platelet function.", "protein": "Coagulation factor V (FV)", "relationship_type": "causal", "source_pmcid": "PMC12130729" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Binds glycosylated cell surface proteins.", "mechanism": "Gal-8 implicated in cell adhesion and immunomodulation relevant to neurodegeneration.", "protein": "Galectin-8", "relationship_type": "biomarker", "source_pmcid": "PMC12130729" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "Glycan-mediated recognition.", "mechanism": "Gal-8 modulates cell-matrix interactions and apoptosis in joint tissues.", "protein": "Galectin-8", "relationship_type": "biomarker", "source_pmcid": "PMC12130729" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation-dependent Gal-8 binding.", "mechanism": "Gal-8 binding to \u03b21-integrin and CD98hc promotes cell adhesion and migration, facilitating tumor progression.", "protein": "\u03b21-integrin", "relationship_type": "causal", "source_pmcid": "PMC12130729" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "CEA is a heavily glycosylated protein; glycosylation affects its stability and detection.", "mechanism": "Elevated serum CEA is associated with SCLC tumor burden; levels decrease with effective therapy.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "NSE is glycosylated, which may affect its secretion and immunoreactivity.", "mechanism": "Serum NSE is a marker for neuroendocrine tumors including SCLC; levels reflect disease activity.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "CYFRA21-1 is an O-glycosylated fragment; glycosylation affects its release and detection.", "mechanism": "CYFRA21-1 fragments in serum indicate epithelial tumor cell turnover; levels decrease with treatment.", "protein": "Cytokeratin-19-fragment (CYFRA21-1)", "protein_enriched": { "function": "Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle", "gene_name": "KRT19", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08727" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "PD-1 is N-glycosylated; glycosylation modulates ligand binding and immune signaling.", "mechanism": "PD-1 mediates immune escape in SCLC; blockade by Tislelizumab restores T cell function.", "protein": "Programmed cell death protein 1 (PD-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "PD-L1 N-glycosylation is critical for its stability and immune checkpoint function.", "mechanism": "PD-L1 binds PD-1 to suppress T cell activity; inhibition enhances anti-tumor immunity.", "protein": "Programmed death-ligand 1 (PD-L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130931" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation affects CEA's immunogenicity and detection in NSCLC.", "mechanism": "CEA is used as a serum biomarker for NSCLC progression and response to therapy.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "O-glycosylation influences CYFRA21-1 fragment release in NSCLC.", "mechanism": "CYFRA21-1 is a sensitive marker for NSCLC, especially squamous cell subtype.", "protein": "CYFRA21-1", "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates PD-1 function in NSCLC immune evasion.", "mechanism": "PD-1 blockade by Tislelizumab improves immune response and survival in NSCLC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects its immune regulatory role.", "mechanism": "PD-L1 expression correlates with immune escape; targeted by checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130931" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may affect NSE's serum levels and detection.", "mechanism": "NSE is less specific but may be elevated in NSCLC with neuroendocrine differentiation.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130931" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "\u03b2-catenin is a glycoprotein; glycosylation may affect its stability and signaling.", "mechanism": "Overactivation of Wnt/\u03b2-catenin pathway promotes HCC cell proliferation, invasion, and metastasis.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "APC is glycosylated; glycosylation may modulate its tumor suppressor function.", "mechanism": "miR-125b positively regulates APC, which suppresses Wnt/\u03b2-catenin signaling and prevents hepatocarcinogenesis.", "protein": "APC", "protein_enriched": { "function": "Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity ", "gene_name": "APC", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60923RB", "G49108TO", "G80920RR", "G28905MY" ], "uniprot_id": "P25054" }, "relationship_type": "protective", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "SMAD2 is glycosylated; glycosylation may affect TGF-\u03b2 signaling.", "mechanism": "miR-125b inhibits EMT by targeting SMAD2, reducing HCC progression.", "protein": "SMAD2", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15796" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "SMAD4 is glycosylated; glycosylation may affect TGF-\u03b2 signaling.", "mechanism": "miR-125b inhibits EMT by targeting SMAD4, reducing HCC progression.", "protein": "SMAD4", "protein_enriched": { "function": "In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 rele", "gene_name": "SMAD4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13485" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "BMI1 is glycosylated; glycosylation may influence its oncogenic activity.", "mechanism": "miR-200 targets BMI1, suppressing tumor development by promoting apoptosis.", "protein": "BMI1", "protein_enriched": { "function": "Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout developme", "gene_name": "BMI1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35226" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130952" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "\u03b3-glutamyl transferase is glycosylated; glycosylation affects its enzymatic activity.", "mechanism": "Correlation between miR-34a-5p expression and \u03b3-glutamyl transferase levels indicates disease progression.", "protein": "\u03b3-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12130952" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect its serum levels and function.", "mechanism": "Correlation between miR-20a-5p expression and albumin levels reflects disease status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "\u03b2-catenin glycosylation may modulate fibrotic signaling.", "mechanism": "Let-7 family miRNAs negatively correlate with fibrosis scores, suggesting regulation of \u03b2-catenin in fibrosis.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC12130952" }, { "confidence": "medium", "disease": "HBV infection", "glycan_involvement": "Glycosylation of \u03b2-catenin may affect its response to viral infection.", "mechanism": "miR-200 expression differs in HBV-positive HCC patients, implicating \u03b2-catenin pathway regulation.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130952" }, { "confidence": "low", "disease": "HCV infection", "glycan_involvement": "Glycosylation of \u03b2-catenin may affect its response to viral infection.", "mechanism": "High miR-155 levels in HCV-infected patients may regulate \u03b2-catenin pathway.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130952" }, { "confidence": "high", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Ferritin is glycosylated, which may affect its stability and serum levels.", "mechanism": "Elevated ferritin reflects hyperinflammation and macrophage activation in MAS.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "high", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Fibrinogen glycosylation influences clotting function and clearance.", "mechanism": "Decreased fibrinogen indicates coagulopathy and systemic inflammation in MAS.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "high", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "sCD25 is N-glycosylated, affecting its secretion and detection.", "mechanism": "Increased sCD25 reflects T-cell activation and immune dysregulation in MAS.", "protein": "Soluble CD25 (sIL-2R alpha)", "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "NK cell surface glycoproteins mediate cytotoxicity and immune recognition.", "mechanism": "Decreased NK cell count/activity is a diagnostic criterion for MAS.", "protein": "Natural Killer (NK) cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "high", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "IVIG glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG is used to treat KD; non-responsiveness is a risk factor for MAS.", "protein": "Intravenous Immunoglobulin (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Gamma globulin glycosylation affects immunomodulatory properties.", "mechanism": "High-dose gamma globulin is used in MAS treatment.", "protein": "Gamma globulin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "CRP glycosylation affects its stability and immune function.", "mechanism": "Elevated CRP indicates acute inflammation in KD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "Ferritin glycosylation may influence serum levels.", "mechanism": "Progressive increase in ferritin may signal KD progression to MAS.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "Glycosylation modulates fibrinogen function.", "mechanism": "Declining fibrinogen may indicate risk of MAS in KD.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "N-glycosylation affects sCD25 secretion.", "mechanism": "Elevated sCD25 may indicate immune activation and risk of MAS in KD.", "protein": "Soluble CD25 (sIL-2R alpha)", "relationship_type": "biomarker", "source_pmcid": "PMC12130957" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "PNPLA3 is a glycoprotein; glycosylation may affect its localization and function in lipid metabolism.", "mechanism": "PNPLA3 variants (rs738408 CT/TT, rs738409 GG) increase hepatic triglyceride accumulation and lipid droplet remodeling, promoting MAFLD onset and progression.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "Glycosylation status may modulate PNPLA3 stability and activity in hepatocytes.", "mechanism": "PNPLA3 I148M variant (rs738409) is associated with progression from fatty liver to cirrhosis due to impaired triglyceride hydrolysis.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation may influence PNPLA3-mediated cellular signaling in carcinogenesis.", "mechanism": "PNPLA3 I148M variant increases risk of hepatocellular carcinoma via chronic lipid accumulation and liver injury.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "Glycosylation may affect PNPLA3's interaction with lipid droplets and inflammatory pathways.", "mechanism": "PNPLA3 rs738409 C/G mutation (I148M) promotes steatohepatitis by increasing hepatic triglyceride and retinyl ester accumulation, leading to inflammation.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation may regulate PNPLA3's trafficking and function in fibrogenic pathways.", "mechanism": "PNPLA3 I148M variant is linked to increased fibrosis severity due to chronic lipid accumulation and ER stress.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation may affect detection and quantification of PNPLA3 in biomarker assays.", "mechanism": "PNPLA3 rs738408 CT/TT and rs738409 GG genotypes serve as genetic biomarkers for MAFLD susceptibility and progression.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130962" }, { "confidence": "medium", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation could influence therapeutic targeting of PNPLA3.", "mechanism": "Targeting PNPLA3 variants may prevent or slow MAFLD progression by restoring normal lipid metabolism.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130962" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation may modulate PNPLA3's enzymatic activity and cellular localization.", "mechanism": "Loss of PNPLA3 function leads to triglyceride and retinyl ester accumulation, ER stress, and hepatocyte damage.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "medium", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation may influence PNPLA3's subcellular trafficking and organelle interactions.", "mechanism": "PNPLA3 variants affect lipid droplet\u2013Golgi dynamics, increasing lipid droplet\u2013Golgi contact sites and altering hepatocyte morphology.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "medium", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation may impact PNPLA3's role in global cellular signaling.", "mechanism": "PNPLA3-I148M induces proteomic and transcriptomic changes resembling all stages of liver disease.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12130962" }, { "confidence": "high", "disease": "TP53-mutated AML", "glycan_involvement": "CD47 is a heavily glycosylated cell surface protein; glycosylation is essential for its interaction with SIRP\u03b1.", "mechanism": "CD47 is overexpressed on AML cells, delivering a 'don't eat me' signal to macrophages and inhibiting phagocytosis; anti-CD47 antibodies (e.g., magrolimab) aim to block this interaction.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "TP53-mutated AML", "glycan_involvement": "TIM-3 is a glycoprotein; glycosylation affects ligand binding and immune regulation.", "mechanism": "TIM-3 is upregulated in AML and contributes to immune evasion; sabatolimab (anti-TIM-3) is being tested to enhance anti-leukemic immunity.", "protein": "TIM-3 (HAVCR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "high", "disease": "TP53-mutated AML", "glycan_involvement": "CD123 is N-glycosylated; glycosylation may influence receptor stability and antibody recognition.", "mechanism": "CD123 is overexpressed on AML blasts; targeted by tagraxofusp and flotetuzumab to induce cytotoxicity.", "protein": "CD123 (IL3RA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "TP53-mutated AML", "glycan_involvement": "PD-1 is glycosylated; glycosylation modulates ligand binding and immune checkpoint function.", "mechanism": "PD-1 is upregulated in TP53-mutated AML, contributing to T cell exhaustion; checkpoint inhibitors (nivolumab, pembrolizumab) aim to restore T cell function.", "protein": "PD-1 (PDCD1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "TP53-mutated AML", "glycan_involvement": "PD-L1 N-glycosylation is critical for stability and immune evasion.", "mechanism": "PD-L1 is expressed on AML cells, inhibiting T cell responses; anti-PD-L1 antibodies (durvalumab) are tested to enhance immunity.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "High-risk Myelodysplastic Syndrome (MDS)", "glycan_involvement": "Glycosylation of CD47 is required for SIRP\u03b1 binding.", "mechanism": "CD47 blockade (magrolimab) in combination with azacitidine shows activity in high-risk MDS, including TP53-mutated cases.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "High-risk Myelodysplastic Syndrome (MDS)", "glycan_involvement": "N-glycosylation may affect antibody binding.", "mechanism": "CD123-targeted therapies (tagraxofusp, flotetuzumab) show responses in high-risk MDS, including TP53-mutated cases.", "protein": "CD123 (IL3RA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "High-risk Myelodysplastic Syndrome (MDS)", "glycan_involvement": "Glycosylation modulates ligand interactions.", "mechanism": "TIM-3 blockade (sabatolimab) in combination with HMAs shows clinical responses in high-risk MDS, including TP53-mutated cases.", "protein": "TIM-3 (HAVCR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "Therapy-related AML", "glycan_involvement": "Glycosylation is necessary for CD47 function.", "mechanism": "CD47 blockade enhances phagocytosis of therapy-related AML cells, including those with TP53 mutations.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "medium", "disease": "Therapy-related AML", "glycan_involvement": "N-glycosylation may influence therapeutic antibody efficacy.", "mechanism": "CD123-targeted therapies are effective in therapy-related AML, including TP53-mutated cases.", "protein": "CD123 (IL3RA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131698" }, { "confidence": "high", "disease": "Pulmonary alveolar proteinosis (PAP)", "glycan_involvement": "GM-CSF glycosylation may affect immunogenicity and antibody recognition.", "mechanism": "Anti-GM-CSF autoantibodies impair alveolar macrophage function, leading to surfactant accumulation.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12132020" }, { "confidence": "high", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Potential glycosylation may influence antigenicity.", "mechanism": "Anti-PL-7 antibodies are diagnostic for ASS and associated with rapidly progressive ILD.", "protein": "PL-7 (Threonyl-tRNA synthetase)", "relationship_type": "biomarker", "source_pmcid": "PMC12132020" }, { "confidence": "medium", "disease": "Pulmonary alveolar proteinosis (PAP)", "glycan_involvement": "CEA is highly glycosylated, affecting its stability and detection.", "mechanism": "Elevated CEA levels correlate with PAP disease activity.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12132020" }, { "confidence": "medium", "disease": "Pulmonary alveolar proteinosis (PAP)", "glycan_involvement": "Glycosylation may affect fragment release and detection.", "mechanism": "Elevated CYFRA21-1 reflects epithelial injury in PAP.", "protein": "CYFRA21-1", "relationship_type": "biomarker", "source_pmcid": "PMC12132020" }, { "confidence": "high", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "KL-6 is a mucin-type glycoprotein; glycosylation critical for function and immunoreactivity.", "mechanism": "KL-6 is elevated in ILD and reflects alveolar epithelial damage.", "protein": "KL-6", "relationship_type": "biomarker", "source_pmcid": "PMC12132020" }, { "confidence": "medium", "disease": "Pulmonary alveolar proteinosis (PAP)", "glycan_involvement": "Glycosylation may affect LDH stability and serum levels.", "mechanism": "Elevated LDH indicates tissue injury in PAP.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC12132020" }, { "confidence": "high", "disease": "Opportunistic infections (Nocardia, Aspergillus)", "glycan_involvement": "Glycosylation may modulate GM-CSF receptor binding and immune response.", "mechanism": "GM-CSF antibody-mediated macrophage dysfunction predisposes to infections.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12132020" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Indirect; glycosylation may affect GM-CSF function.", "mechanism": "PAP-associated inflammation and immobility increase risk of thrombosis.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12132020" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "Anti-PL-7 antibodies trigger alveolar inflammation and fibrosis.", "protein": "PL-7 (Threonyl-tRNA synthetase)", "relationship_type": "causal", "source_pmcid": "PMC12132020" }, { "confidence": "low", "disease": "Deep vein thrombosis", "glycan_involvement": "Indirect; glycosylation may affect GM-CSF activity.", "mechanism": "PAP-related immune dysfunction and immobility contribute to thrombosis.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12132020" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Heavily O-glycosylated decameric repeats (DR) in the extracellular domain are essential for antiviral activity.", "mechanism": "Acts as an HIV-1 restriction factor by steric hindrance, blocking virion attachment to target cells.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "O-glycosylation of DRs contributes to backbone extension and spatial exclusion.", "mechanism": "DR domain is required for exclusion of HIV Env from virion particles (spatial hindrance).", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "O-glycosylation at threonine residues in DRs is critical for backbone rigidity and antiviral function.", "mechanism": "Number of DRs correlates with cumulative antiviral potency; single DR retains basal activity.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Transferred O-glycosylated DR domain mediates steric hindrance in hybrid proteins.", "mechanism": "DR domain\u2019s antiviral activity is transferrable; insertion into CD2 confers partial anti-HIV activity.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Not detailed in this article.", "mechanism": "Inhibits HIV-1 infectivity and virion release at low dosages.", "protein": "SERINC5", "protein_enriched": { "function": "Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an ", "gene_name": "PNO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRX1" }, "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Restricts HIV-1 infectivity, especially in absence of Vif protein.", "protein": "APOBEC3G", "protein_enriched": { "function": "DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:12808465, PubMed:165277", "gene_name": "APOBEC3G", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC16" }, "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Loss of O-glycosylated DRs removes steric hindrance function.", "mechanism": "Deletion of all DRs abolishes anti-HIV activity, demonstrating necessity for restriction.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "causal", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation and sequence determine backbone extension and potency.", "mechanism": "Sequence variation among DRs affects individual antiviral potency.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Heavy O-glycosylation increases backbone rigidity and extension.", "mechanism": "Steric hindrance by extended, glycosylated DR backbone blocks antibody binding to cell surface receptors.", "protein": "PSGL-1 (P-selectin glycoprotein ligand-1)", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "O-glycosylated DR domain is responsible for antiviral effect in hybrid protein.", "mechanism": "Hybrid CD2-DR proteins acquire partial anti-HIV activity via DR-mediated steric hindrance.", "protein": "CD2-DR hybrid", "relationship_type": "protective", "source_pmcid": "PMC12132433" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation forms a shield that masks neutralizing epitopes, aiding immune evasion.", "mechanism": "Mediates viral entry into hepatocytes via receptor binding and membrane fusion.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycans on E2 mask conserved neutralizing epitopes, affecting antibody recognition.", "mechanism": "E2 binds host receptors (CD81, SR-B1, LDLr) and is targeted by broadly neutralizing antibodies.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132513" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation influences folding, stability, and antigenicity.", "mechanism": "E1 associates with E2 to form the functional heterodimer and participates in membrane fusion.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycan shield contributes to persistence by evading immune clearance.", "mechanism": "Persistent infection via E1E2-mediated entry leads to chronic liver inflammation.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation aids immune evasion, promoting chronicity.", "mechanism": "Long-term HCV infection driven by E1E2 entry/fusion leads to liver fibrosis and cirrhosis.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycan shield maintains viral persistence, increasing cancer risk.", "mechanism": "Chronic HCV infection via E1E2 promotes oncogenic transformation in hepatocytes.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Oligomannose enrichment improves immunogenicity by mimicking native viral glycan shield.", "mechanism": "Target for vaccine design; presentation of native-like glycoprotein elicits neutralizing antibodies.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132513" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation status affects antibody binding and diagnostic accuracy.", "mechanism": "E2-specific antibodies indicate exposure and immune response to HCV.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycan trimming or enrichment modulates epitope exposure and antibody response.", "mechanism": "Induction of broadly neutralizing antibodies against E1E2 can prevent infection.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Oligomannose-type glycan enrichment increases neutralizing antibody elicitation.", "mechanism": "Multivalent display on nanoparticles enhances immunogenicity for vaccine development.", "protein": "E1E2 glycoprotein heterodimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132513" }, { "confidence": "high", "disease": "Bovine Respiratory Syncytial Virus infection", "glycan_involvement": "Glycosylation is essential for proper folding and function, facilitating host cell binding.", "mechanism": "Mediates viral attachment to host respiratory epithelial cells, initiating infection.", "protein": "G glycoprotein (BRSV)", "protein_enriched": { "function": "Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160' (By similarity). Required for high-level Shh responses in the developi", "gene_name": "Cdk20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9JHU3" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "high", "disease": "Bovine Respiratory Syncytial Virus infection", "glycan_involvement": "Glycosylation modulates fusogenic activity and immune evasion.", "mechanism": "Promotes fusion of viral and host cell membranes, enabling viral entry.", "protein": "F protein (BRSV)", "protein_enriched": { "function": "", "gene_name": "Palmd", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9JHU2" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "medium", "disease": "Bovine Respiratory Disease Complex (BRDC)", "glycan_involvement": "Glycosylation enhances immune evasion and persistence in the respiratory tract.", "mechanism": "Facilitates BRSV infection, a major viral component of BRDC.", "protein": "G glycoprotein (BRSV)", "protein_enriched": { "function": "Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160' (By similarity). Required for high-level Shh responses in the developi", "gene_name": "Cdk20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9JHU3" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "medium", "disease": "Bovine Respiratory Disease Complex (BRDC)", "glycan_involvement": "Glycosylation affects antigenicity and fusion efficiency.", "mechanism": "Enables BRSV entry, contributing to BRDC pathogenesis.", "protein": "F protein (BRSV)", "protein_enriched": { "function": "", "gene_name": "Palmd", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9JHU2" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "high", "disease": "Bovine Parainfluenza Virus Type 3 infection", "glycan_involvement": "Glycosylation is critical for receptor binding and enzymatic activity.", "mechanism": "Mediates viral attachment and neuraminidase activity, facilitating entry and spread.", "protein": "HN glycoprotein (BPIV3)", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 18, "glytoucan_ids": [], "uniprot_id": "P11225" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "high", "disease": "Bovine Parainfluenza Virus Type 3 infection", "glycan_involvement": "Glycosylation regulates fusion activity and immune recognition.", "mechanism": "Drives membrane fusion between virus and host cell, allowing infection.", "protein": "F protein (BPIV3)", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Interacts with murine CEACAM1 to mediate viral entry", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 18, "glytoucan_ids": [], "uniprot_id": "P11224" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "medium", "disease": "Bovine Respiratory Disease Complex (BRDC)", "glycan_involvement": "Glycosylation supports viral spread and immune evasion.", "mechanism": "BPIV3 infection via HN glycoprotein contributes to BRDC.", "protein": "HN glycoprotein (BPIV3)", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 18, "glytoucan_ids": [], "uniprot_id": "P11225" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "medium", "disease": "Bovine Respiratory Disease Complex (BRDC)", "glycan_involvement": "Glycosylation modulates fusion and antigenicity.", "mechanism": "BPIV3 F protein enables infection, a component of BRDC.", "protein": "F protein (BPIV3)", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Interacts with murine CEACAM1 to mediate viral entry", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 18, "glytoucan_ids": [], "uniprot_id": "P11224" }, "relationship_type": "causal", "source_pmcid": "PMC12132865" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "GP is processed into Gn and Gc by host proteases; glycosylation is required for function.", "mechanism": "GP mediates virion assembly and entry into target cells, essential for SFTSV infection.", "protein": "SFTSV glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gn is a glycoprotein; glycosylation is necessary for its activity.", "mechanism": "Gn is involved in viral entry and assembly.", "protein": "Gn (N-terminal glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gc is a glycoprotein; glycosylation is required for fusion activity.", "mechanism": "Gc mediates fusion and entry of SFTSV into host cells.", "protein": "Gc (C-terminal glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "No direct glycosylation reported for SAFA in this context.", "mechanism": "SAFA acts as an RNA sensor, activating innate immunity and restricting SFTSV replication.", "protein": "SAFA (hnRNP U)", "relationship_type": "protective", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "No direct glycosylation reported for NSs.", "mechanism": "NSs inhibits host antiviral immune responses by degrading SAFA via autophagy.", "protein": "SFTSV NSs", "relationship_type": "causal", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "No direct glycosylation reported for SQSTM1 in this context.", "mechanism": "SQSTM1 mediates selective autophagic degradation of SAFA, facilitating immune evasion by SFTSV.", "protein": "SQSTM1/p62", "relationship_type": "causal", "source_pmcid": "PMC12132933" }, { "confidence": "medium", "disease": "Vesicular stomatitis virus (VSV) infection", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SAFA restricts VSV replication by activating antiviral responses.", "protein": "SAFA (hnRNP U)", "relationship_type": "protective", "source_pmcid": "PMC12132933" }, { "confidence": "medium", "disease": "Herpes simplex virus 1 (HSV1) infection", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SAFA restricts HSV1 replication.", "protein": "SAFA (hnRNP U)", "relationship_type": "protective", "source_pmcid": "PMC12132933" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SAFA restricts HIV-1 replication.", "protein": "SAFA (hnRNP U)", "relationship_type": "protective", "source_pmcid": "PMC12132933" }, { "confidence": "medium", "disease": "Porcine epidemic diarrhea virus infection", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SAFA negatively regulates innate immune response against PEDV.", "protein": "SAFA (hnRNP U)", "relationship_type": "regulatory", "source_pmcid": "PMC12132933" }, { "confidence": "high", "disease": "Acquired von Willebrand Disease (vWD)", "glycan_involvement": "vWF is a heavily glycosylated protein; glycosylation affects its stability and interactions.", "mechanism": "Abnormal function or clearance of vWF leads to bleeding symptoms; can be due to adsorption, autoantibodies, or increased proteolysis.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Diffuse Large B-cell Lymphoma (DLBCL)", "glycan_involvement": "Glycosylation may affect vWF's interaction with tumor cells or immune system.", "mechanism": "DLBCL-associated inflammation or tumor factors disrupt vWF function, causing acquired vWD with Type 2B phenotype.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation modulates vWF binding affinity to GPIb\u03b1.", "mechanism": "Enhanced vWF-platelet GPIb\u03b1 binding (Type 2B phenotype) leads to platelet clearance and thrombocytopenia.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Inherited Type 2B von Willebrand Disease", "glycan_involvement": "Glycosylation status may influence mutant vWF function.", "mechanism": "Gain-of-function mutations in vWF increase binding to GPIb\u03b1, causing bleeding and thrombocytopenia.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12133210" }, { "confidence": "medium", "disease": "Acquired von Willebrand Disease (vWD)", "glycan_involvement": "Factor VIII is glycosylated, affecting its plasma stability.", "mechanism": "Factor VIII is an acute-phase reactant; elevated levels may mask underlying vWD.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Acquired von Willebrand Disease (vWD)", "glycan_involvement": "Glycosylation affects antigenicity and assay results.", "mechanism": "vWF antigen and activity levels are used to diagnose vWD, but may be falsely normal during inflammation.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Inherited Type 2B von Willebrand Disease", "glycan_involvement": "GPIb\u03b1 is glycosylated; glycosylation modulates receptor function.", "mechanism": "Mutant vWF binds GPIb\u03b1 with increased affinity, causing platelet aggregation and clearance.", "protein": "Glycoprotein Ib alpha (GPIb\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12133210" }, { "confidence": "medium", "disease": "Diffuse Large B-cell Lymphoma (DLBCL)", "glycan_involvement": "Altered glycosylation may contribute to vWF dysfunction in malignancy.", "mechanism": "vWF dysfunction may indicate paraneoplastic bleeding in DLBCL.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12133210" }, { "confidence": "medium", "disease": "Acquired von Willebrand Disease (vWD)", "glycan_involvement": "Therapeutic vWF preparations rely on correct glycosylation for efficacy.", "mechanism": "Restoration of vWF function or levels resolves bleeding symptoms.", "protein": "von Willebrand factor (vWF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133210" }, { "confidence": "medium", "disease": "Acquired von Willebrand Disease (vWD)", "glycan_involvement": "Glycosylation affects multimer formation and stability.", "mechanism": "vWF multimer analysis can help subtype vWD, but may be misleading during acute-phase reactions.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12133210" }, { "confidence": "high", "disease": "Post-COVID-19 syndrome", "glycan_involvement": "ADA1 forms complexes with glycosylated CD26, facilitating adhesion.", "mechanism": "ADA1 upregulation in endothelium promotes vascular inflammation via increased adenosine degradation and immune cell adhesion.", "protein": "ADA1", "relationship_type": "causal", "source_pmcid": "PMC12133555" }, { "confidence": "high", "disease": "Post-COVID-19 syndrome", "glycan_involvement": "CD26 glycosylation is essential for ADA1 binding and complex formation.", "mechanism": "CD26 upregulation on endothelium anchors ADA1, enhancing immune cell adhesion and inflammation.", "protein": "CD26", "relationship_type": "causal", "source_pmcid": "PMC12133555" }, { "confidence": "high", "disease": "Endothelial inflammation", "glycan_involvement": "Complex formation depends on glycosylated CD26.", "mechanism": "ADA1-CD26 interaction acts as an adhesion molecule, increasing monocyte/macrophage binding to endothelium.", "protein": "ADA1-CD26 complex", "relationship_type": "causal", "source_pmcid": "PMC12133555" }, { "confidence": "medium", "disease": "Microvascular dysfunction", "glycan_involvement": "ADA2 is a glycoprotein; glycosylation may affect secretion/activity.", "mechanism": "Increased ADA2 activity in monocytes/macrophages correlates with microvascular dysfunction in post-COVID.", "protein": "ADA2", "relationship_type": "biomarker", "source_pmcid": "PMC12133555" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ADA1 binds glycosylated CD26 on endothelium.", "mechanism": "Elevated endothelial cell-surface ADA1 activity is associated with atherosclerosis.", "protein": "ADA1", "relationship_type": "biomarker", "source_pmcid": "PMC12133555" }, { "confidence": "medium", "disease": "Aortic valve stenosis", "glycan_involvement": "ADA1-CD26 glycoprotein interaction implicated.", "mechanism": "Increased ADA1 activity in endothelium is linked to aortic valve stenosis.", "protein": "ADA1", "relationship_type": "biomarker", "source_pmcid": "PMC12133555" }, { "confidence": "high", "disease": "Post-COVID-19 syndrome", "glycan_involvement": "Spike protein is heavily glycosylated, affecting CD26 interaction.", "mechanism": "Spike protein competes with ADA1 for CD26 binding, modulating endothelial inflammation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12133555" }, { "confidence": "high", "disease": "Endothelial inflammation", "glycan_involvement": "gp120 glycosylation is critical for its inhibitory function.", "mechanism": "gp120 inhibits ADA1-CD26 interaction, reducing immune cell adhesion and endothelial inflammation.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD26 glycosylation required for ligand binding.", "mechanism": "CD26 inhibitors (e.g., sitagliptin) may reduce COVID-19 severity by blocking viral and ADA1 binding.", "protein": "CD26", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133555" }, { "confidence": "medium", "disease": "Endothelial inflammation", "glycan_involvement": "ICAM-1 is a glycoprotein; glycosylation affects cell adhesion.", "mechanism": "Elevated sICAM-1 levels indicate endothelial activation/inflammation in post-COVID.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133555" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "Anti-MOG antibodies are used to differentiate MS from other demyelinating diseases.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is glycosylated; glycosylation may affect antibody binding.", "mechanism": "Anti-AQP4 antibodies are diagnostic for NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Neurosarcoidosis", "glycan_involvement": "IgG glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG used as immunomodulatory therapy in neurosarcoidosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Sarcoidosis", "glycan_involvement": "ACE is glycosylated; glycosylation affects enzyme stability and activity.", "mechanism": "Serum ACE levels are used as a supportive biomarker for sarcoidosis diagnosis.", "protein": "Angiotensin-Converting Enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "high", "disease": "Neurosarcoidosis", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation may affect receptor binding and immune response.", "mechanism": "TNF-\u03b1 inhibitors (e.g., infliximab) are used for refractory neurosarcoidosis.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke", "glycan_involvement": "IgG glycosylation influences anti-inflammatory effects.", "mechanism": "IVIG administered for possible autoimmune-mediated CNS disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Optic Neuritis", "glycan_involvement": "Glycosylation modulates MOG antigenicity.", "mechanism": "Anti-MOG antibodies help distinguish MOG-associated optic neuritis.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "low", "disease": "Neurosarcoidosis", "glycan_involvement": "Glycosylation affects ACE function.", "mechanism": "ACE levels may support diagnosis but were normal in this case.", "protein": "Angiotensin-Converting Enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke", "glycan_involvement": "Glycosylation may modulate TNF-\u03b1 activity.", "mechanism": "Inflammatory cytokines like TNF-\u03b1 contribute to vascular inflammation and stroke risk.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12133606" }, { "confidence": "medium", "disease": "Neurosarcoidosis", "glycan_involvement": "Glycosylation affects IgG function and immune response.", "mechanism": "Oligoclonal bands (IgG) in CSF indicate CNS inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133606" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns can affect its detection and specificity.", "mechanism": "Elevated serum AFP is used to indicate presence and risk stratification of HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133621" }, { "confidence": "high", "disease": "Microvascular invasion in HCC", "glycan_involvement": "Glycosylation variants of AFP (e.g., AFP-L3) are more specific for aggressive HCC with MVI.", "mechanism": "High AFP levels are associated with increased risk of MVI in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133621" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "HBsAg is a glycoprotein; its glycosylation affects immune recognition and viral persistence.", "mechanism": "Chronic HBV infection (indicated by HBsAg positivity) is a major risk factor for HCC development.", "protein": "Hepatitis B surface antigen", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03138" }, "relationship_type": "causal", "source_pmcid": "PMC12133621" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation of HBsAg modulates host immune response and chronicity.", "mechanism": "Chronic HBV infection leads to liver cirrhosis, predisposing to HCC.", "protein": "Hepatitis B surface antigen", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03138" }, "relationship_type": "causal", "source_pmcid": "PMC12133621" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT reflects hepatic steatosis and oxidative stress in MASLD.", "protein": "gamma-glutamyl transferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA1) whose glycosylation modulates function.", "mechanism": "Low HDL-C is associated with increased MASLD risk due to impaired lipid transport.", "protein": "high-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Lipoproteins contain glycoproteins; glycosylation influences lipid metabolism.", "mechanism": "Elevated triglycerides promote hepatic fat accumulation in MASLD.", "protein": "triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HbA1c is a glycated protein; glycation reflects chronic hyperglycemia.", "mechanism": "Elevated HbA1c indicates poor glycemic control, a risk factor for MASLD.", "protein": "hemoglobin A1c (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "medium", "disease": "arterial stiffness", "glycan_involvement": "AST is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "AST/ALT ratio correlates with arterial stiffness, reflecting liver injury and metabolic dysfunction.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "medium", "disease": "arterial stiffness", "glycan_involvement": "ALT is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "ALT levels, in ratio with AST, are linked to arterial stiffness and MASLD.", "protein": "alanine aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Albumin is glycosylated; glycosylation affects half-life and function.", "mechanism": "Low albumin may reflect advanced MASLD and liver dysfunction.", "protein": "albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Insulin is glycosylated; glycosylation affects receptor binding and clearance.", "mechanism": "Insulin resistance promotes hepatic fat accumulation and MASLD.", "protein": "insulin", "relationship_type": "causal", "source_pmcid": "PMC12133722" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ApoB glycosylation modulates lipoprotein assembly and secretion.", "mechanism": "Elevated ApoB indicates increased VLDL secretion and hepatic lipid export in MASLD.", "protein": "apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12133722" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ApoA1 glycosylation affects HDL function and anti-inflammatory properties.", "mechanism": "ApoA1 promotes cholesterol efflux, reducing hepatic steatosis risk.", "protein": "apolipoprotein A1", "protein_enriched": { "function": "Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acylt", "gene_name": "APOA1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P02647" }, "relationship_type": "protective", "source_pmcid": "PMC12133722" }, { "confidence": "high", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "STAB1 is a heavily glycosylated scavenger receptor; glycosylation is essential for its cell-surface localization and function in cell-cell interactions.", "mechanism": "STAB1 hypomethylation leads to overexpression in endothelial cells, promoting ECM production, tube formation, and immune cell adhesion, contributing to intimal thickening and vascular stenosis.", "protein": "Stabilin-1 (STAB1)", "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "SORT1 is N-glycosylated, which affects its trafficking and receptor function.", "mechanism": "Overexpressed SORT1 in endothelial cells enhances angiogenesis in MMD.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134390" }, { "confidence": "high", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "Fibronectin is glycosylated, which modulates its ECM assembly and cell adhesion properties.", "mechanism": "Upregulated in endothelial cells with MMD serum and STAB1 overexpression, contributing to ECM accumulation and intimal thickening.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "high", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "Collagen IV is glycosylated, influencing its stability and ECM network formation.", "mechanism": "Upregulated in endothelial cells with MMD serum and STAB1 overexpression, contributing to ECM accumulation and vascular pathology.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "NCAM1 glycosylation regulates cell-cell adhesion and immune cell recruitment.", "mechanism": "CD56 bright NK cells interact with enlarged endothelial cell cytoskeleton, promoting EC proliferation and angiogenesis in MMD.", "protein": "CD56 (NCAM1)", "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Intracerebral haemorrhage", "glycan_involvement": "Glycosylation of STAB1 is required for immune cell interactions.", "mechanism": "STAB1 mediates immune cell adhesion to vascular wall, contributing to inflammation and endothelial dysfunction.", "protein": "Stabilin-1 (STAB1)", "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "RNF213 knockdown promotes endothelial cell proliferation, migration, and tube formation, affecting angiogenesis in MMD.", "protein": "RNF213", "protein_enriched": { "function": "Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immuni", "gene_name": "RNF213", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G31852PQ", "G70994MS" ], "uniprot_id": "Q63HN8" }, "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "Glycosylation status may affect STAB1 targeting and function.", "mechanism": "Targeting STAB1 may modulate endothelial-immune cell interactions and ECM production, potentially mitigating vascular stenosis.", "protein": "Stabilin-1 (STAB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134390" }, { "confidence": "high", "disease": "Moyamoya disease (MMD)", "glycan_involvement": "Glycosylation may influence detection and biomarker utility.", "mechanism": "STAB1 hypomethylation and overexpression serve as a biomarker for MMD subtype and disease activity.", "protein": "Stabilin-1 (STAB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134390" }, { "confidence": "medium", "disease": "Intracerebral haemorrhage", "glycan_involvement": "NCAM1 glycosylation modulates immune cell-endothelial interactions.", "mechanism": "NK cells expressing CD56 exert cytotoxic effects on cerebrovascular endothelial cells, contributing to vascular injury.", "protein": "CD56 (NCAM1)", "relationship_type": "causal", "source_pmcid": "PMC12134390" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation forms the protective glycocalyx layer; its degradation leads to dysfunction.", "mechanism": "Reduced glycocalyx thickness (higher PBR) indicates increased endothelial permeability and dysfunction.", "protein": "Endothelial glycocalyx", "relationship_type": "biomarker", "source_pmcid": "PMC12134458" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "Glycoprotein layer integrity modulates vascular compliance.", "mechanism": "Thinner glycocalyx (higher PBR) is associated with increased arterial stiffness.", "protein": "Endothelial glycocalyx", "relationship_type": "biomarker", "source_pmcid": "PMC12134458" }, { "confidence": "medium", "disease": "Cardiac performance impairment", "glycan_involvement": "Loss of glycoprotein layer affects myocardial performance via vascular effects.", "mechanism": "Glycocalyx degradation correlates with impaired ventriculoarterial interaction and cardiac function.", "protein": "Endothelial glycocalyx", "relationship_type": "biomarker", "source_pmcid": "PMC12134458" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation maintains barrier function and cell-cell interactions.", "mechanism": "Intact glycocalyx (lower PBR) protects against endothelial dysfunction.", "protein": "Endothelial glycocalyx", "relationship_type": "protective", "source_pmcid": "PMC12134458" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "Glycoprotein structure supports vessel compliance.", "mechanism": "Healthy glycocalyx reduces arterial stiffness by maintaining vascular elasticity.", "protein": "Endothelial glycocalyx", "relationship_type": "protective", "source_pmcid": "PMC12134458" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD40 is a glycoprotein; glycosylation affects its cell surface expression and ligand binding, influencing immune signaling.", "mechanism": "Higher circulating CD40 levels causally associated with reduced MS risk; modulates immune cell infiltration, promotes adaptive immune regulation, inhibits TGF-\u03b2 signaling, and supports mitochondrial and nucleotide metabolism.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12134489" }, { "confidence": "high", "disease": "Relapsing-Remitting MS (RRMS)", "glycan_involvement": "Glycosylation modulates CD40 stability and immune cell interactions.", "mechanism": "Downregulated in RRMS patient blood; higher CD40 expression linked to better prognosis and immune regulation.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CXCL10 is glycosylated, affecting chemokine gradient formation and immune cell recruitment.", "mechanism": "Higher CXCL10 levels associated with increased MS risk (nominal significance).", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation required for receptor function and ligand binding.", "mechanism": "Higher LIF receptor levels associated with increased MS risk (nominal significance).", "protein": "LIF receptor", "protein_enriched": { "function": "Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells", "gene_name": "LIFR", "glycan_count": 12, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G76535FN", "G46503DX", "G49108TO", "G80920RR", "G01650EU", "G31852PQ", "G63041LO", "G57321FI", "G43769HG", "G62765YT", "G93718GY", "G57776ZS" ], "uniprot_id": "P42702" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "Higher FLT-3L levels associated with lower PD risk (nominal significance).", "protein": "FLT-3L", "protein_enriched": { "function": "Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. Required for the development of B cell", "gene_name": "FLT3LG", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P49771" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation modulates receptor binding and signaling.", "mechanism": "Higher TGF-\u03b1 levels associated with lower PD risk (nominal significance).", "protein": "TGF-\u03b1", "relationship_type": "protective/causal", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation required for receptor stability and immune signaling.", "mechanism": "Higher TNFRSF9 levels associated with lower PD risk (nominal significance).", "protein": "TNFRSF9", "protein_enriched": { "function": "Receptor for TNFSF9/4-1BBL. Conveys a signal that enhances CD8(+) T-cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors (Probable)", "gene_name": "TNFRSF9", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G32156ZV", "G27058EU" ], "uniprot_id": "Q07011" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects cytokine secretion and receptor interaction.", "mechanism": "Higher IL-17A levels associated with increased PD risk (nominal significance).", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Glycosylation may affect protein stability and apoptotic signaling.", "mechanism": "Higher caspase-8 levels associated with increased ALS risk (nominal significance).", "protein": "Caspase-8", "protein_enriched": { "function": "Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic devel", "gene_name": "CASP8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14790" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Glycosylation modulates cytokine activity and immune response.", "mechanism": "Higher TNFSF14 levels associated with lower IS risk (nominal significance).", "protein": "TNFSF14", "relationship_type": "protective/causal", "source_pmcid": "PMC12134489" }, { "confidence": "medium", "disease": "Sclerosing Angiomatoid Nodular Transformation (SANT)", "glycan_involvement": "IgG4 glycosylation modulates immune response and fibrotic activity.", "mechanism": "IgG4-related sclerosing disease is hypothesized to contribute to SANT pathogenesis via immune-mediated fibrosis.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12134817" }, { "confidence": "high", "disease": "IgG4-related sclerosing disease", "glycan_involvement": "Altered glycosylation of IgG4 affects effector functions and tissue deposition.", "mechanism": "Elevated IgG4 is a hallmark of IgG4-related disease, driving fibroinflammatory changes.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134817" }, { "confidence": "low", "disease": "Sclerosing Angiomatoid Nodular Transformation (SANT)", "glycan_involvement": "EBV glycoproteins mediate host cell entry and immune modulation via glycan interactions.", "mechanism": "EBV infection is proposed to trigger inflammatory and stromal changes leading to SANT.", "protein": "Epstein-Barr virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12134817" }, { "confidence": "high", "disease": "Epstein-Barr virus infection", "glycan_involvement": "Glycosylation of EBV envelope proteins is critical for infectivity and immune evasion.", "mechanism": "EBV glycoproteins are essential for viral entry and persistence in host cells.", "protein": "Epstein-Barr virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12134817" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and immune recognition.", "mechanism": "Acts as an autoantigen; immune response against MOG induces demyelination in MS and EAE models.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12135090" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates APP processing and aggregation.", "mechanism": "APP cleavage produces amyloid-beta, forming plaques that drive neuroinflammation and neurodegeneration.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12135090" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation may regulate receptor function and cell surface expression.", "mechanism": "IL-17RA mediates IL-17A signaling, promoting CNS inflammation; blocking IL-17RA ameliorates disease in models.", "protein": "IL-17 receptor A (IL-17RA)", "protein_enriched": { "function": "Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911", "gene_name": "IL17RA", "glycan_count": 11, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G62765YT", "G80920RR", "G25079LO", "G37818NZ", "G46503DX", "G83460ZZ", "G83633GK", "G69268QO", "G41247ZX", "G49108TO" ], "uniprot_id": "Q96F46" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135090" }, { "confidence": "high", "disease": "Autism spectrum disorder", "glycan_involvement": "As a cytokine, glycosylation may affect secretion and stability.", "mechanism": "Maternal IL-17A elevation during pregnancy alters fetal neurodevelopment, leading to ASD-like behaviors.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135090" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence cytokine-receptor interactions.", "mechanism": "IL-17A from Th17/\u03b3\u03b4 T cells induces neuroinflammation, neuronal death, and cognitive decline; neutralization is protective.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12135090" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect cytokine stability and receptor binding.", "mechanism": "IL-17A promotes dopaminergic neuronal death via microglia and TNF\u03b1; blocking IL-17A is neuroprotective in models.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12135090" }, { "confidence": "medium", "disease": "Major depressive disorder", "glycan_involvement": "Glycosylation may affect cytokine function.", "mechanism": "Elevated IL-17A and Th17 cells correlate with depression severity; neutralization alleviates symptoms in models.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12135090" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation critical for ligand binding and immune cell adhesion.", "mechanism": "ICAM-1 mediates Th17 cell infiltration into CNS; blocking ICAM-1 reduces neuronal death in PD models.", "protein": "Intercellular adhesion molecule 1 (ICAM-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135090" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Potential O-glycosylation may affect aggregation and immune recognition.", "mechanism": "Acts as an autoantigen; T cell responses to \u03b1-synuclein exacerbate PD pathology.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal/autoantigen", "source_pmcid": "PMC12135090" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Some HSPs are glycoproteins; glycosylation may modulate immunogenicity.", "mechanism": "Recognized by \u03b3\u03b4 T cells, contributing to autoimmune responses in MS.", "protein": "Heat shock proteins (HSPs)", "relationship_type": "autoantigen", "source_pmcid": "PMC12135090" }, { "confidence": "high", "disease": "SLE", "glycan_involvement": "Glycosylation required for MHC II stability and trafficking.", "mechanism": "CQ/HCQ inhibit antigen presentation via MHC II, reducing autoreactive T cell activation.", "protein": "MHC II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136085" }, { "confidence": "high", "disease": "SLE", "glycan_involvement": "Glycosylation modulates TLR7 localization and ligand recognition.", "mechanism": "Aberrant TLR7 signaling drives type I interferon production and autoimmunity; CQ/HCQ inhibit TLR7 activation.", "protein": "TLR7", "relationship_type": "causal", "source_pmcid": "PMC12136085" }, { "confidence": "high", "disease": "SLE", "glycan_involvement": "Glycosylation affects TLR9 trafficking and function.", "mechanism": "TLR9 activation promotes autoantibody production; CQ/HCQ block TLR9 signaling.", "protein": "TLR9", "relationship_type": "causal", "source_pmcid": "PMC12136085" }, { "confidence": "high", "disease": "RA", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion and receptor binding.", "mechanism": "CQ/HCQ suppress TNF-\u03b1 production, reducing inflammation and joint damage.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136085" }, { "confidence": "high", "disease": "RA", "glycan_involvement": "Glycosylation required for IL-6 stability and signaling.", "mechanism": "CQ/HCQ decrease IL-6 levels, mitigating inflammatory responses.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136085" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Glycosylation modulates IL-10 secretion and activity.", "mechanism": "CQ/HCQ upregulate IL-10, promoting anti-inflammatory effects.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12136085" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Glycosylation essential for cathepsin trafficking and activity.", "mechanism": "CQ/HCQ inhibit lysosomal cathepsins, blocking antigen processing and presentation.", "protein": "Cathepsins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136085" }, { "confidence": "medium", "disease": "SS", "glycan_involvement": "Heavily glycosylated; glycosylation affects lysosomal localization.", "mechanism": "LAMP3 mRNA expression in salivary glands predicts HCQ response.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136085" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Glycosylation required for surface expression and ligand binding.", "mechanism": "HCQ increases KLRG1 expression on NK cells, modulating immune activity.", "protein": "KLRG1", "relationship_type": "biomarker", "source_pmcid": "PMC12136085" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Binds glycan structures; glycosylation determines ligand specificity.", "mechanism": "HCQ targets LGALS8, affecting autophagy and immune regulation.", "protein": "LGALS8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136085" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect its synaptic localization and PET tracer binding.", "mechanism": "SV2A PET imaging ([11C]UCB-J) quantifies synaptic density, which is reduced in AD, especially in hippocampus and entorhinal cortex.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "SV2A glycosylation status may influence synaptic vesicle function.", "mechanism": "SV2A PET imaging detects synaptic loss in Parkinson's disease.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Huntington's disease", "glycan_involvement": "SV2A glycosylation may modulate synaptic vesicle trafficking.", "mechanism": "SV2A PET imaging reveals synaptic density changes in Huntington's disease.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "SV2A glycosylation could affect synaptic function.", "mechanism": "SV2A PET imaging shows altered synaptic density in schizophrenia.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Down syndrome", "glycan_involvement": "SV2A glycosylation may be altered in Down syndrome.", "mechanism": "SV2A PET imaging detects synaptic changes in Down syndrome.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Synaptophysin is a glycoprotein; glycosylation may affect its stability and localization.", "mechanism": "Immunolabeling of synaptophysin quantifies synaptic vesicle density, which is reduced in AD.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation and toxicity.", "mechanism": "Neurofibrillary tau tangles (NFTs) accumulate and drive neurodegeneration and synaptic loss.", "protein": "Tau (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect SV2A's function and PET tracer binding.", "mechanism": "SV2A PET imaging may identify individuals with resilience to AD pathology and guide therapy.", "protein": "SV2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136093" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau glycosylation influences NFT formation and detection.", "mechanism": "NFT burden measured by PET correlates with synaptic loss and disease progression.", "protein": "Tau (MAPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12136093" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate SV2A's role in synaptic resilience.", "mechanism": "SV2A levels may reflect compensatory synaptic mechanisms in early AD.", "protein": "SV2A", "relationship_type": "protective", "source_pmcid": "PMC12136093" }, { "confidence": "high", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "AMH is a glycoprotein; glycosylation is essential for its secretion and bioactivity.", "mechanism": "AMH is secreted by granulosa cells and maintains ovarian reserve by inhibiting primordial follicle recruitment and modulating follicular sensitivity to FSH.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12136117" }, { "confidence": "medium", "disease": "Chemotherapy-induced ovarian dysfunction", "glycan_involvement": "Glycosylation required for AMH stability and function.", "mechanism": "AMH diminishes chemotherapy-induced ovarian dysfunction, reducing risk of POI.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "protective", "source_pmcid": "PMC12136117" }, { "confidence": "high", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "FSH is a glycoprotein; glycosylation affects receptor binding and half-life.", "mechanism": "Elevated FSH is a marker of POI; secretome therapy reduces FSH by restoring ovarian feedback.", "protein": "Follicle-Stimulating Hormone (FSH)", "protein_enriched": { "function": "Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled recepto", "gene_name": "FSHB", "glycan_count": 28, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08146BT", "G32246SI", "G79745PG", "G90789YQ", "G05850WN", "G43753QH", "G45495MK", "G50131RA", "G51177EP", "G51497BL", "G06356OH", "G15169WU", "G16155TD", "G17689DH", "G22310AV", "G45209NR", "G45560HM", "G47518TP", "G48414YA", "G52527GH", "G56318NV", "G66088HZ", "G69834CE", "G77252PU", "G78030KJ", "G91413ZX", "G94531EZ", "G98366ZJ" ], "uniprot_id": "P01225" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12136117" }, { "confidence": "high", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Low E2 is characteristic of POI; secretome therapy increases E2, indicating restored folliculogenesis.", "protein": "Estradiol (E2)", "relationship_type": "biomarker", "source_pmcid": "PMC12136117" }, { "confidence": "medium", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "VEGF glycosylation modulates receptor interaction and stability.", "mechanism": "VEGF in secretome promotes angiogenesis and tissue repair, supporting follicular survival.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic target/protective", "source_pmcid": "PMC12136117" }, { "confidence": "medium", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "IGF glycosylation affects bioactivity and receptor binding.", "mechanism": "IGF in secretome stimulates follicular development and has anti-apoptotic effects.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "therapeutic target/protective", "source_pmcid": "PMC12136117" }, { "confidence": "high", "disease": "Premature Ovarian Failure (POF)", "glycan_involvement": "Glycosylation required for AMH secretion and activity.", "mechanism": "AMH levels reflect ovarian reserve; increased AMH after secretome therapy suggests improved ovarian function.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12136117" }, { "confidence": "high", "disease": "Premature Ovarian Failure (POF)", "glycan_involvement": "FSH glycosylation critical for function.", "mechanism": "High FSH is a diagnostic marker for POF; secretome therapy lowers FSH via restored ovarian feedback.", "protein": "Follicle-Stimulating Hormone (FSH)", "protein_enriched": { "function": "Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled recepto", "gene_name": "FSHB", "glycan_count": 28, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08146BT", "G32246SI", "G79745PG", "G90789YQ", "G05850WN", "G43753QH", "G45495MK", "G50131RA", "G51177EP", "G51497BL", "G06356OH", "G15169WU", "G16155TD", "G17689DH", "G22310AV", "G45209NR", "G45560HM", "G47518TP", "G48414YA", "G52527GH", "G56318NV", "G66088HZ", "G69834CE", "G77252PU", "G78030KJ", "G91413ZX", "G94531EZ", "G98366ZJ" ], "uniprot_id": "P01225" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12136117" }, { "confidence": "medium", "disease": "Chemotherapy-induced ovarian dysfunction", "glycan_involvement": "Glycosylation modulates VEGF activity.", "mechanism": "VEGF promotes angiogenesis and tissue repair, mitigating ovarian damage.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "protective", "source_pmcid": "PMC12136117" }, { "confidence": "medium", "disease": "Premature Ovarian Failure (POF)", "glycan_involvement": "Glycosylation affects IGF stability and function.", "mechanism": "IGF supports follicular survival and development, aiding recovery from POF.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "therapeutic target/protective", "source_pmcid": "PMC12136117" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and trafficking.", "mechanism": "APP is sequentially cleaved by BACE1 and \u03b3-secretase to generate A\u03b2, which aggregates to form plaques in AD.", "protein": "\u03b2-amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12136892" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation state can influence aggregation.", "mechanism": "A\u03b2 aggregation forms senile plaques, a hallmark of AD pathology.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12136892" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is N-glycosylated; glycosylation affects its stability and activity.", "mechanism": "BACE1 initiates A\u03b2 generation by cleaving APP; inhibition or silencing reduces A\u03b2 production.", "protein": "BACE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "HSA is a glycoprotein; glycosylation may affect its interaction with A\u03b2.", "mechanism": "HSA modification on nanocarrier enhances targeting and removal of A\u03b2.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "therapeutic_target (delivery/clearance aid)", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "RVG is a glycoprotein; glycosylation may influence receptor binding.", "mechanism": "RVG29 peptide targets nanocarrier to brain via nAChR on BBB and neurons.", "protein": "Rabies Virus Glycoprotein (RVG29)", "relationship_type": "therapeutic_target (delivery aid)", "source_pmcid": "PMC12136892" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates BACE1 function.", "mechanism": "Elevated BACE1 expression/activity is associated with increased A\u03b2 and AD progression.", "protein": "BACE1", "relationship_type": "biomarker", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 glycosylation state may affect metal binding and aggregation.", "mechanism": "Chelation of Zn2+ from A\u03b2/Zn2+ polymers by CHA inhibits A\u03b2 aggregation.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APP cleavage and A\u03b2 production.", "mechanism": "APP processing imbalance leads to increased A\u03b2 in AD.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136892" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect BACE1-siRNA delivery efficiency.", "mechanism": "BACE1-siRNA delivered by nanocarrier reduces BACE1 expression, lowering A\u03b2 generation.", "protein": "BACE1", "relationship_type": "protective (when silenced)", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "HSA glycosylation may modulate A\u03b2 binding.", "mechanism": "HSA-modified nanocarrier enhances A\u03b2 removal from brain.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "protective (via A\u03b2 clearance)", "source_pmcid": "PMC12136892" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "DBP is a glycoprotein; deglycosylation affects function.", "mechanism": "Low DBP levels found in MS; increasing GSN and DBP may be therapeutic.", "protein": "Vitamin D Binding Protein (DBP)", "protein_enriched": { "function": "Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation", "gene_name": "GC", "glycan_count": 11, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G06247RL", "G40574BA", "G45395BF", "G48414YA", "G59626AS", "G70232NH", "G70888PK", "G49108TO", "G65562ZE", "G74722FL" ], "uniprot_id": "P02774" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137432" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MOG is a CNS glycoprotein; glycosylation critical for antigenicity.", "mechanism": "Vitamin D increases MOG expression, promoting remyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "PLP is glycosylated; glycosylation affects myelin stability.", "mechanism": "Vitamin D supplementation increases PLP, aiding myelin repair.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "MBP is subject to post-translational modifications; glycosylation may modulate immune recognition.", "mechanism": "Vitamin D increases MBP, supporting remyelination.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "GSN is glycosylated; glycosylation affects secretion and function.", "mechanism": "Low GSN in MS; increasing GSN may be protective.", "protein": "Gelsolin (GSN)", "protein_enriched": { "function": "Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly o", "gene_name": "GSN", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G43417UB", "G57321FI", "G29068FM", "G53434XO" ], "uniprot_id": "P06396" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Progranulin is glycosylated; glycosylation modulates neuroinflammatory signaling.", "mechanism": "Altered progranulin levels in PD with dyskinesia; involved in inflammation.", "protein": "Progranulin", "relationship_type": "biomarker", "source_pmcid": "PMC12137432" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation affects A\u03b2 generation.", "mechanism": "Vitamin D suppresses A\u03b2 production by modulating APP processing enzymes.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect filament assembly.", "mechanism": "Low vitamin D associated with elevated GFAP, indicating astrocyte activation.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "S100B is glycosylated; glycosylation influences secretion.", "mechanism": "Low vitamin D linked to increased S100B, reflecting glial activation.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137432" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Klotho is a glycoprotein; glycosylation is essential for stability and function.", "mechanism": "Low Klotho in CSF correlates with PD severity; Klotho deficiency impairs dopaminergic system.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12137432" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "gp120 is heavily glycosylated; glycosylation stabilizes its structure and may influence amyloidogenic peptide exposure.", "mechanism": "gp120 forms amyloid-like fibrils (GAPs) in brain and CSF, causing neuronal loss, dendritic and synaptic damage, and neuroinflammation.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC12137973" }, { "confidence": "high", "disease": "HIV-associated dementia", "glycan_involvement": "Glycosylation of gp120 affects peptide processing and aggregation propensity.", "mechanism": "gp120-derived amyloid fibrils accumulate in CSF and brain, correlating with severe dementia in HIV+ patients.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC12137973" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate gp120 neurotoxicity and Tau phosphorylation.", "mechanism": "gp120-induced phosphorylated Tau (Ser396) is a marker of neurodegeneration, overlapping with AD pathology.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137973" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect its aggregation and response.", "mechanism": "GFAP upregulation and activation mark astrocytic response to gp120-induced injury and amyloid formation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137973" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "CCR5 is glycosylated; glycosylation affects receptor function and ligand binding.", "mechanism": "Amyloid fibrils from gp120 activate CCR5 in neurons and astrocytes, leading to CREB downregulation and neurotoxicity; CCR5 inhibition (MVC) is neuroprotective.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12137973" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "Tau glycosylation may modulate aggregation and phosphorylation.", "mechanism": "Phosphorylated Tau (Ser396) is elevated in gp120-expressing mice, indicating neurodegeneration.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137973" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "SYP glycosylation may affect synaptic vesicle function.", "mechanism": "Decreased SYP expression indicates presynaptic damage in gp120-induced HAND.", "protein": "Synaptophysin (SYP)", "relationship_type": "biomarker", "source_pmcid": "PMC12137973" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "MAP-2 glycosylation may influence microtubule stability.", "mechanism": "Reduced MAP-2 marks dendritic injury in gp120-induced HAND.", "protein": "MAP-2", "protein_enriched": { "function": "The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules", "gene_name": "Map2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G33416PL", "G40926MX" ], "uniprot_id": "P20357" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137973" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "Glycosylation of gp120 may regulate peptide release and aggregation.", "mechanism": "Amyloidogenic peptides from gp120 (GP-3-6, GP-18) form neurotoxic fibrils, causing neuronal and glial cytotoxicity.", "protein": "HIV-1 gp120 (GAPs: GP-3-6, GP-18 peptides)", "relationship_type": "causal", "source_pmcid": "PMC12137973" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "CCR5 glycosylation modulates antagonist binding and receptor activity.", "mechanism": "CCR5 antagonist (MVC) reverses gp120/GAPs-induced neurotoxicity and cognitive deficits.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137973" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Heavily O-glycosylated mucin-like domains modulate attachment and immune evasion.", "mechanism": "Mediates viral attachment to host cells via CX3CR1 and HSPGs, initiating infection.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "causal", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "N-glycosylation affects folding, stability, and antigenicity.", "mechanism": "Promotes fusion of viral and host cell membranes, enabling viral entry.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Cell-specific glycosylation alters infectivity and host response.", "mechanism": "Facilitates infection of lower airway epithelial cells, leading to inflammation and airway obstruction.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "causal", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "N-glycosylation modulates fusion activity and immune recognition.", "mechanism": "Induces syncytia formation and airway epithelial damage.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12138085" }, { "confidence": "medium", "disease": "Asthma (post-RSV)", "glycan_involvement": "O-glycosylation in mucin-like domains influences immune modulation.", "mechanism": "Alters immune response, impairs Th1 cytokine production, and increases airway hyperreactivity.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "causal", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Glycosylation affects antibody binding and efficacy.", "mechanism": "Targeted by monoclonal antibodies and small molecules to block viral attachment.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "N-glycans influence neutralizing epitope exposure.", "mechanism": "Targeted by monoclonal antibodies (e.g., palivizumab, nirsevimab) and fusion inhibitors.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "sG retains glycosylation, mimicking membrane G for immune evasion.", "mechanism": "Secreted G (sG) acts as antigenic decoy, binding neutralizing antibodies.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "immune_evasion", "source_pmcid": "PMC12138085" }, { "confidence": "medium", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Glycosylation state can affect detection and immune response.", "mechanism": "Surface expression and conformation indicate infection stage and therapeutic response.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138085" }, { "confidence": "low", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Glycosylation status not detailed; presumed minor.", "mechanism": "Minor role in viral entry and pathogenesis; not a major therapeutic target.", "protein": "SH protein", "protein_enriched": { "function": "Ribonucleocapsid-associated protein that interacts with the phosphoprotein (P), thereby increasing replication accuracy and processivity of the polymerase complex", "gene_name": "P/V/C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03424" }, "relationship_type": "contributory", "source_pmcid": "PMC12138085" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation modulates receptor function and plasma stability.", "mechanism": "Lower plasma EGFR predicts faster decline in language and processing speed; involved in cell signaling and neuroprotection.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Cell-surface glycosylation affects receptor interactions.", "mechanism": "Lower plasma RTN4RL2 predicts faster decline in language and visuospatial skills; regulates synapse formation and A\u03b2 production.", "protein": "RTN4RL2", "protein_enriched": { "function": "Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG (By similarity). Plays a functionally redundant role in postnatal brain developmen", "gene_name": "RTN4RL2", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G53677UQ", "G57321FI", "G46503DX", "G49018RC", "G83460ZZ" ], "uniprot_id": "Q86UN3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Likely N-glycosylated, affecting secretion and stability.", "mechanism": "Lower plasma NOMO2 predicts faster decline in processing speed; part of ER-associated protein complex.", "protein": "NOMO2", "protein_enriched": { "function": "Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2 (PubMed:15302918). Inhibits expression of the gluconeogenesis enzyme PCK2 through inhibition of NR2C2 activity (By similarity). A", "gene_name": "JAZF1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q86VZ6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "C-type lectin domain mediates glycan binding.", "mechanism": "Lower plasma CLEC3B predicts faster decline in processing speed; involved in plasminogen activation and tissue remodeling.", "protein": "CLEC3B", "protein_enriched": { "function": "Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis. Plays a role in retinal function (PubMed:35331648)", "gene_name": "CLEC3B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05452" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation influences plasma half-life.", "mechanism": "Lower plasma A1BG predicts faster decline in executive function, especially in MCI.", "protein": "A1BG", "protein_enriched": { "function": "", "gene_name": "A1BG", "glycan_count": 29, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G03596YS", "G06247RL", "G06356OH", "G08293MJ", "G10486CT", "G15038BD", "G27947YN", "G37868ZX", "G42358LZ", "G42962KI", "G43669FQ", "G44215PV", "G47518TP", "G47737VJ", "G48414YA", "G52527GH", "G59626AS", "G86182NS", "G87051GH", "G88374WZ", "G94917XT", "G29068FM", "G43417UB", "G49108TO", "G20425TQ", "G22140GZ", "G36131WL", "G50045TK" ], "uniprot_id": "P04217" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Catalyzes O-glycosylation, impacting many glycoproteins.", "mechanism": "Lower plasma GALNT1 predicts faster decline in visuospatial skills; initiates O-glycosylation of proteins.", "protein": "GALNT1", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:8690719, P", "gene_name": "GALNT1", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G70441OD", "G08918WF", "G27058EU", "G45395BF", "G49108TO" ], "uniprot_id": "Q10472" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation affects inhibitor activity.", "mechanism": "Lower plasma SERPINA4 predicts faster decline in visuospatial skills; inhibits serine proteases, modulates inflammation.", "protein": "SERPINA4", "protein_enriched": { "function": "Inhibits human amidolytic and kininogenase activities of tissue kallikrein. Inhibition is achieved by formation of an equimolar, heat- and SDS-stable complex between the inhibitor and the enzyme, and ", "gene_name": "SERPINA4", "glycan_count": 39, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G03644CB", "G04854VP", "G06247RL", "G09831WQ", "G11115RO", "G13910DJ", "G15169WU", "G47518TP", "G53075ES", "G66088HZ", "G70232NH", "G92081HT", "G94917XT", "G06356OH", "G08918WF", "G11911BT", "G26330YA", "G27947YN", "G40574BA", "G40834TG", "G44215PV", "G45395BF", "G48414YA", "G49906RN", "G51413EV", "G56518TU", "G59626AS", "G70619PT", "G70888PK", "G75983OB", "G82830MN", "G89098OM", "G92275SC", "G01650EU", "G23294PN", "G41882MT", "G52527GH", "G93656SY" ], "uniprot_id": "P29622" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation modulates function and clearance.", "mechanism": "Lower plasma SERPINA5 predicts faster decline in visuospatial skills; associated with tau pathology.", "protein": "SERPINA5", "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation required for complement assembly.", "mechanism": "Lower plasma C8A predicts faster decline in visuospatial skills; part of complement membrane attack complex.", "protein": "C8A", "protein_enriched": { "function": "Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane ", "gene_name": "C8A", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06356OH", "G08918WF", "G10486CT", "G27058EU", "G27126ED", "G28681TP", "G40574BA", "G45395BF", "G48414YA", "G50045TK", "G57776ZU", "G59626AS", "G70619PT", "G72747WU", "G95865ZB", "G61491DK", "G49108TO" ], "uniprot_id": "P07357" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "low", "disease": "Cognitive decline", "glycan_involvement": "Potential glycosylation affects secretion.", "mechanism": "Lower plasma ALDOB predicts faster decline in visuospatial skills; glycolytic enzyme, possible metabolic link.", "protein": "ALDOB", "relationship_type": "biomarker", "source_pmcid": "PMC12138273" }, { "confidence": "high", "disease": "Type 2 Autoimmune Pancreatitis (AIP-2)", "glycan_involvement": "LRG is a glycoprotein; glycosylation is essential for its stability and serum detection.", "mechanism": "Serum LRG levels correlate with disease activity and inflammation in AIP-2.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138893" }, { "confidence": "high", "disease": "Type 2 Autoimmune Pancreatitis (AIP-2)", "glycan_involvement": "IL-8 is glycosylated, which may affect its secretion and stability.", "mechanism": "Serum IL-8 levels reflect disease activity, likely due to neutrophil recruitment and GEL formation.", "protein": "Interleukin-8", "relationship_type": "biomarker", "source_pmcid": "PMC12138893" }, { "confidence": "medium", "disease": "Type 2 Autoimmune Pancreatitis (AIP-2)", "glycan_involvement": "CRP is glycosylated; glycosylation affects its serum half-life.", "mechanism": "CRP is a conventional inflammation marker but less sensitive than LRG/IL-8 for AIP-2 activity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12138893" }, { "confidence": "high", "disease": "Type 1 Autoimmune Pancreatitis (AIP-1)", "glycan_involvement": "IgG4 is N-glycosylated; glycosylation modulates immune function.", "mechanism": "Elevated serum IgG4 is a diagnostic marker for AIP-1.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138893" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation is required for LRG's serum stability and detection.", "mechanism": "LRG is a known marker for disease activity in UC.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138893" }, { "confidence": "medium", "disease": "Type 2 Autoimmune Pancreatitis (AIP-2)", "glycan_involvement": "Glycosylation may affect IL-8's bioactivity and receptor interactions.", "mechanism": "IL-8 overexpression in ductal epithelium promotes neutrophil infiltration and GEL formation.", "protein": "Interleukin-8", "relationship_type": "causal", "source_pmcid": "PMC12138893" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Absence of post-translational modifications (including glycosylation) may contribute to misfolding.", "mechanism": "Mutations (e.g., E100K) in SOD1 cause protein misfolding and aggregation, leading to ALS pathology.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "causal", "source_pmcid": "PMC12138904" }, { "confidence": "high", "disease": "Familial ALS (fALS)", "glycan_involvement": "Decreased post-translational modifications (potentially glycosylation) implicated in instability.", "mechanism": "SOD1 mutations (e.g., E100K) increase aggregation propensity, accelerating disease progression.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "causal", "source_pmcid": "PMC12138904" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "No direct glycan targeting; modulation of aggregation may indirectly relate to glycosylation status.", "mechanism": "SOD1 aggregation is targeted by small molecules (e.g., flavonoids) to inhibit amyloid formation.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138904" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Altered glycosylation may affect aggregation propensity.", "mechanism": "Aggregated SOD1 is a marker of ALS pathology.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138904" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Not specified.", "mechanism": "Polyphenolic flavonoids (e.g., Fisetin) inhibit SOD1 aggregation, which may be protective in Parkinson's.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "protective (potential)", "source_pmcid": "PMC12138904" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Not specified.", "mechanism": "Flavonoids inhibit amyloidogenic proteins, including SOD1, possibly reducing Alzheimer's pathology.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "protective (potential)", "source_pmcid": "PMC12138904" }, { "confidence": "low", "disease": "ATTR amyloidosis", "glycan_involvement": "Not specified.", "mechanism": "Flavonoids (e.g., Fisetin, Peonidin) have anti-amyloidogenic effects on SOD1, possibly relevant to ATTR.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "protective (potential)", "source_pmcid": "PMC12138904" }, { "confidence": "low", "disease": "Type 2 diabetes", "glycan_involvement": "Not specified.", "mechanism": "Polyphenolic flavonoids with anti-aggregation properties may have beneficial effects in diabetes.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "protective (potential)", "source_pmcid": "PMC12138904" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "No direct glycan involvement; effect is on protein conformation.", "mechanism": "Fisetin binds E100K SOD1, stabilizes structure, reduces \u03b2-sheet content, and inhibits aggregation.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138904" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Other flavonoids (Puerarin, Peonidin) also bind SOD1 and reduce aggregation, but less effectively than Fisetin.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138904" }, { "confidence": "high", "disease": "NGLY1 deficiency (NGLY1-CDDG)", "glycan_involvement": "Defective removal of N-glycans from misfolded glycoproteins.", "mechanism": "Loss of NGLY1 impairs deglycosylation of misfolded glycoproteins, disrupting ERAD and proteostasis.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "causal", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "Congenital alacrima", "glycan_involvement": "AQP1 is a glycoprotein; its expression is regulated by NGLY1-mediated pathways.", "mechanism": "Reduced AQP1 expression in eyes/brain leads to impaired tear secretion.", "protein": "Aquaporin 1 (AQP1)", "protein_enriched": { "function": "Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues (PubMed:1373524, PubMed:23219802). Could also be per", "gene_name": "AQP1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29972" }, "relationship_type": "causal", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "Neuromuscular abnormalities", "glycan_involvement": "Failure to deglycosylate misfolded glycoproteins disrupts neuronal proteostasis.", "mechanism": "NGLY1 deficiency leads to neural loss and mitochondrial fragmentation, causing muscle atrophy.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "causal", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "NGLY1 deficiency (NGLY1-CDDG)", "glycan_involvement": "Linked to glycoprotein degradation via ERAD.", "mechanism": "Downregulation and accumulation of poly-ubiquitinated proteins indicate impaired protein degradation.", "protein": "Ubiquitin B (UBB)", "protein_enriched": { "function": "Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a pol", "gene_name": "UBB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P0CG47" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138962" }, { "confidence": "medium", "disease": "NGLY1 deficiency (NGLY1-CDDG)", "glycan_involvement": "UBE3A acts downstream of glycoprotein deglycosylation.", "mechanism": "Reduced UBE3A expression in brain correlates with neurological dysfunction.", "protein": "Ubiquitin-protein ligase E3A (UBE3A)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:1920", "gene_name": "UBE3A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q05086" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "NGLY1 deficiency (NGLY1-CDDG)", "glycan_involvement": "Misfolded glycoproteins aggregate when not properly deglycosylated.", "mechanism": "Amyloid aggregation in brain reflects impaired proteostasis due to NGLY1 loss.", "protein": "Amyloid fibrils", "relationship_type": "biomarker", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "NGLY1 deficiency (NGLY1-CDDG)", "glycan_involvement": "AQP1 glycosylation and expression are affected by NGLY1 activity.", "mechanism": "AQP1 reduction in brain/eye is a hallmark of NGLY1 deficiency.", "protein": "Aquaporin 1 (AQP1)", "protein_enriched": { "function": "Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues (PubMed:1373524, PubMed:23219802). Could also be per", "gene_name": "AQP1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29972" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "Angelman syndrome", "glycan_involvement": "UBE3A is part of the ubiquitin-proteasome system handling glycoprotein degradation.", "mechanism": "UBE3A loss-of-function causes Angelman syndrome; parallels with NGLY1 deficiency.", "protein": "Ubiquitin-protein ligase E3A (UBE3A)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:1920", "gene_name": "UBE3A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q05086" }, "relationship_type": "causal", "source_pmcid": "PMC12138962" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "UBE3A regulates degradation of glycoproteins prone to aggregation.", "mechanism": "Reduced UBE3A expression is associated with amyloid accumulation in Alzheimer's.", "protein": "Ubiquitin-protein ligase E3A (UBE3A)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:1920", "gene_name": "UBE3A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q05086" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycoprotein misfolding and failed deglycosylation promote amyloidogenesis.", "mechanism": "Amyloid aggregation is a common mechanism in neurodegeneration, also seen in NGLY1 deficiency.", "protein": "Amyloid fibrils", "relationship_type": "causal", "source_pmcid": "PMC12138962" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "gp130 is a glycoprotein required for receptor complex formation.", "mechanism": "gp130 mediates IL-6 trans-signalling, which drives inflammation in RA; blockade reduces disease activity.", "protein": "glycoprotein 130 (gp130)", "protein_enriched": { "function": "Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6", "gene_name": "IL6ST", "glycan_count": 48, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G08918WF", "G27058EU", "G38663NM", "G41071NU", "G45395BF", "G56784JY", "G62765YT", "G80920RR", "G81263BG", "G84452RH", "G87661QW", "G90659AW", "G92275SC", "G49108TO", "G00912UN", "G10486CT", "G28622IK", "G37881RL", "G42124LM", "G43089EG", "G52527GH", "G59536GA", "G59626AS", "G72790NZ", "G33791AF", "G22310AV", "G82830MN", "G26436YP", "G55412XP", "G72787SB", "G81295CK", "G62461SM", "G59324HL", "G01650EU", "G02815KT", "G08290VR", "G22573RC", "G28541PG", "G29299MO", "G31852PQ", "G37399XV", "G45504EY", "G47644PP", "G63041LO", "G70101JE", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P40189" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL-6R is a glycoprotein; glycosylation affects receptor stability and function.", "mechanism": "IL-6R blockade inhibits both classical and trans-signalling, reducing inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "gp130 glycosylation is essential for cell surface expression and signalling.", "mechanism": "Persistent IL-6/gp130 signalling promotes tumorigenesis via JAK/STAT3 pathway.", "protein": "glycoprotein 130 (gp130)", "protein_enriched": { "function": "Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6", "gene_name": "IL6ST", "glycan_count": 48, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G08918WF", "G27058EU", "G38663NM", "G41071NU", "G45395BF", "G56784JY", "G62765YT", "G80920RR", "G81263BG", "G84452RH", "G87661QW", "G90659AW", "G92275SC", "G49108TO", "G00912UN", "G10486CT", "G28622IK", "G37881RL", "G42124LM", "G43089EG", "G52527GH", "G59536GA", "G59626AS", "G72790NZ", "G33791AF", "G22310AV", "G82830MN", "G26436YP", "G55412XP", "G72787SB", "G81295CK", "G62461SM", "G59324HL", "G01650EU", "G02815KT", "G08290VR", "G22573RC", "G28541PG", "G29299MO", "G31852PQ", "G37399XV", "G45504EY", "G47644PP", "G63041LO", "G70101JE", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P40189" }, "relationship_type": "causal", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Therapeutic is a glycoprotein fusion protein mimicking gp130.", "mechanism": "Selective inhibition of IL-6 trans-signalling by sgp130Fc reduces inflammation and induces remission.", "protein": "Olamkicept (sgp130Fc)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "gp130 glycosylation required for function.", "mechanism": "IL-6 trans-signalling via gp130 promotes vascular inflammation and atherogenesis.", "protein": "glycoprotein 130 (gp130)", "protein_enriched": { "function": "Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6", "gene_name": "IL6ST", "glycan_count": 48, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G08918WF", "G27058EU", "G38663NM", "G41071NU", "G45395BF", "G56784JY", "G62765YT", "G80920RR", "G81263BG", "G84452RH", "G87661QW", "G90659AW", "G92275SC", "G49108TO", "G00912UN", "G10486CT", "G28622IK", "G37881RL", "G42124LM", "G43089EG", "G52527GH", "G59536GA", "G59626AS", "G72790NZ", "G33791AF", "G22310AV", "G82830MN", "G26436YP", "G55412XP", "G72787SB", "G81295CK", "G62461SM", "G59324HL", "G01650EU", "G02815KT", "G08290VR", "G22573RC", "G28541PG", "G29299MO", "G31852PQ", "G37399XV", "G45504EY", "G47644PP", "G63041LO", "G70101JE", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P40189" }, "relationship_type": "causal", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "IL-6R blockade reduces cytokine storm and inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "medium", "disease": "Systemic sclerosis", "glycan_involvement": "gp130 glycosylation required for receptor activity.", "mechanism": "gp130-mediated IL-6 signalling contributes to fibrosis and inflammation.", "protein": "glycoprotein 130 (gp130)", "protein_enriched": { "function": "Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6", "gene_name": "IL6ST", "glycan_count": 48, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G08918WF", "G27058EU", "G38663NM", "G41071NU", "G45395BF", "G56784JY", "G62765YT", "G80920RR", "G81263BG", "G84452RH", "G87661QW", "G90659AW", "G92275SC", "G49108TO", "G00912UN", "G10486CT", "G28622IK", "G37881RL", "G42124LM", "G43089EG", "G52527GH", "G59536GA", "G59626AS", "G72790NZ", "G33791AF", "G22310AV", "G82830MN", "G26436YP", "G55412XP", "G72787SB", "G81295CK", "G62461SM", "G59324HL", "G01650EU", "G02815KT", "G08290VR", "G22573RC", "G28541PG", "G29299MO", "G31852PQ", "G37399XV", "G45504EY", "G47644PP", "G63041LO", "G70101JE", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P40189" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Castleman\u2019s disease", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "IL-6R blockade reduces lymphoproliferation and inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Cytokine release syndrome", "glycan_involvement": "gp130 glycosylation required for signalling.", "mechanism": "gp130-mediated IL-6 signalling drives hyperinflammation.", "protein": "glycoprotein 130 (gp130)", "protein_enriched": { "function": "Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6", "gene_name": "IL6ST", "glycan_count": 48, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G08918WF", "G27058EU", "G38663NM", "G41071NU", "G45395BF", "G56784JY", "G62765YT", "G80920RR", "G81263BG", "G84452RH", "G87661QW", "G90659AW", "G92275SC", "G49108TO", "G00912UN", "G10486CT", "G28622IK", "G37881RL", "G42124LM", "G43089EG", "G52527GH", "G59536GA", "G59626AS", "G72790NZ", "G33791AF", "G22310AV", "G82830MN", "G26436YP", "G55412XP", "G72787SB", "G81295CK", "G62461SM", "G59324HL", "G01650EU", "G02815KT", "G08290VR", "G22573RC", "G28541PG", "G29299MO", "G31852PQ", "G37399XV", "G45504EY", "G47644PP", "G63041LO", "G70101JE", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P40189" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138989" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "IL-11R is a glycoprotein; glycosylation required for function.", "mechanism": "IL-11/gp130 signalling implicated in tumorigenesis, similar to IL-6.", "protein": "Interleukin-11 receptor (IL-11R)", "relationship_type": "causal", "source_pmcid": "PMC12138989" }, { "confidence": "high", "disease": "Chronic Schistosomiasis mansoni", "glycan_involvement": "IFNG is a glycoprotein; glycosylation may affect its stability and secretion but not directly discussed.", "mechanism": "IFNG expression is significantly higher in chronic schistosomiasis patients before treatment, indicating ongoing inflammation.", "protein": "Interferon gamma (IFNG)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "IFNG", "glycan_count": 41, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G08520NM", "G10219AA", "G14260UH", "G18938DW", "G20030CU", "G20425TQ", "G23453IV", "G23863VK", "G29011JC", "G29857RC", "G31936TA", "G33609NS", "G36191CD", "G39188ZX", "G39213VZ", "G40702WU", "G45359RY", "G46687AB", "G47012YE", "G49874UX", "G49889OJ", "G50045TK", "G52064IJ", "G55220VL", "G60145BJ", "G61751GZ", "G63889NK", "G64527OM", "G68668TB", "G72797UR", "G75727PF", "G78059CC", "G79809MM", "G80858MF", "G80966KZ", "G81295CK", "G83161QT", "G86357DX", "G90093AU" ], "uniprot_id": "P01579" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139366" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate IFNG receptor interactions; not directly discussed.", "mechanism": "IFNG prevents progression of fibrosis by inhibiting TGF-\u03b2 signaling and fibroblast activation.", "protein": "Interferon gamma (IFNG)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "IFNG", "glycan_count": 41, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G08520NM", "G10219AA", "G14260UH", "G18938DW", "G20030CU", "G20425TQ", "G23453IV", "G23863VK", "G29011JC", "G29857RC", "G31936TA", "G33609NS", "G36191CD", "G39188ZX", "G39213VZ", "G40702WU", "G45359RY", "G46687AB", "G47012YE", "G49874UX", "G49889OJ", "G50045TK", "G52064IJ", "G55220VL", "G60145BJ", "G61751GZ", "G63889NK", "G64527OM", "G68668TB", "G72797UR", "G75727PF", "G78059CC", "G79809MM", "G80858MF", "G80966KZ", "G81295CK", "G83161QT", "G86357DX", "G90093AU" ], "uniprot_id": "P01579" }, "relationship_type": "protective", "source_pmcid": "PMC12139366" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "No direct glycan involvement; acts via gene regulation.", "mechanism": "miR-10a increases fibroblast proliferation and TGF-\u03b21 expression, promoting fibrosis.", "protein": "miR-10a", "relationship_type": "causal", "source_pmcid": "PMC12139366" }, { "confidence": "high", "disease": "Chronic Schistosomiasis mansoni", "glycan_involvement": "None.", "mechanism": "miR-10a expression in PBMCs is low and not a useful biomarker for inflammation in chronic schistosomiasis.", "protein": "miR-10a", "relationship_type": "biomarker", "source_pmcid": "PMC12139366" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation is important for secretion and activity.", "mechanism": "TGF-\u03b21 promotes fibrosis via activation of fibroblasts and extracellular matrix production.", "protein": "Transforming Growth Factor beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12139366" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "SMAD7 inhibits TGF-\u03b2 signaling, reducing fibrosis.", "protein": "SMAD7", "protein_enriched": { "function": "Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associati", "gene_name": "SMAD7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15105" }, "relationship_type": "protective", "source_pmcid": "PMC12139366" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "None.", "mechanism": "TGF-\u03b2 increases miR-10a expression in intestinal mucosa; IFNG and TNF inhibit miR-10a.", "protein": "miR-10a", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12139366" }, { "confidence": "low", "disease": "Crohn's disease", "glycan_involvement": "IFNG glycosylation may affect function; not discussed.", "mechanism": "IFNG inhibits miR-10a expression, modulating inflammation.", "protein": "Interferon gamma (IFNG)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "IFNG", "glycan_count": 41, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G08520NM", "G10219AA", "G14260UH", "G18938DW", "G20030CU", "G20425TQ", "G23453IV", "G23863VK", "G29011JC", "G29857RC", "G31936TA", "G33609NS", "G36191CD", "G39188ZX", "G39213VZ", "G40702WU", "G45359RY", "G46687AB", "G47012YE", "G49874UX", "G49889OJ", "G50045TK", "G52064IJ", "G55220VL", "G60145BJ", "G61751GZ", "G63889NK", "G64527OM", "G68668TB", "G72797UR", "G75727PF", "G78059CC", "G79809MM", "G80858MF", "G80966KZ", "G81295CK", "G83161QT", "G86357DX", "G90093AU" ], "uniprot_id": "P01579" }, "relationship_type": "regulatory", "source_pmcid": "PMC12139366" }, { "confidence": "medium", "disease": "Chronic Schistosomiasis mansoni", "glycan_involvement": "None.", "mechanism": "miR-10a is an IFNG antagonist and inhibits Th1 response, but not significant in PBMCs in this context.", "protein": "miR-10a", "relationship_type": "regulatory", "source_pmcid": "PMC12139366" }, { "confidence": "low", "disease": "Chronic Schistosomiasis mansoni", "glycan_involvement": "Glycosylation may affect therapeutic efficacy.", "mechanism": "IFNG may be targeted to modulate immune response and fibrosis in schistosomiasis.", "protein": "Interferon gamma (IFNG)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "IFNG", "glycan_count": 41, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G08520NM", "G10219AA", "G14260UH", "G18938DW", "G20030CU", "G20425TQ", "G23453IV", "G23863VK", "G29011JC", "G29857RC", "G31936TA", "G33609NS", "G36191CD", "G39188ZX", "G39213VZ", "G40702WU", "G45359RY", "G46687AB", "G47012YE", "G49874UX", "G49889OJ", "G50045TK", "G52064IJ", "G55220VL", "G60145BJ", "G61751GZ", "G63889NK", "G64527OM", "G68668TB", "G72797UR", "G75727PF", "G78059CC", "G79809MM", "G80858MF", "G80966KZ", "G81295CK", "G83161QT", "G86357DX", "G90093AU" ], "uniprot_id": "P01579" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139366" }, { "confidence": "high", "disease": "Visceral leishmaniasis (VL)", "glycan_involvement": "N- and O-glycosylation motifs present in L. infantum GP63; glycosylation may affect protein stability, immunogenicity, and host interaction.", "mechanism": "GP63 facilitates entry of Leishmania infantum into host macrophages, contributing to parasite survival and pathogenesis.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12140206" }, { "confidence": "high", "disease": "Cutaneous leishmaniasis (CL)", "glycan_involvement": "L. major GP63 has N- and O-glycosylation; L. tropica GP63 has only O-glycosylation, potentially affecting antigenicity and expression.", "mechanism": "GP63 on L. major and L. tropica mediates parasite adhesion to host cells and immune evasion, driving CL pathogenesis.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12140206" }, { "confidence": "high", "disease": "Leishmaniasis (general)", "glycan_involvement": "Glycosylation motifs may influence epitope presentation and vaccine efficacy.", "mechanism": "GP63 is a major surface antigen and immunogenic target for vaccine development against multiple Leishmania species.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140206" }, { "confidence": "high", "disease": "Leishmaniasis (general)", "glycan_involvement": "Glycosylation may affect epitope solubility and antigenicity in diagnostic platforms.", "mechanism": "GP63-derived epitopes can be used in serological diagnostic assays for leishmaniasis.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Visceral leishmaniasis (VL)", "glycan_involvement": "N-glycosylation may enhance immunogenicity and protein folding, improving vaccine efficacy.", "mechanism": "Vaccination with GP63 (especially L. infantum variant) reduces parasite burden and induces protective immune responses in experimental models.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis (CL)", "glycan_involvement": "N- and O-glycosylation may affect antigen stability and immune recognition.", "mechanism": "GP63-based vaccines (L. major variant) confer resistance to L. major challenge in animal models.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Leishmaniasis (general)", "glycan_involvement": "Conserved glycosylation motifs may facilitate broad immune recognition.", "mechanism": "Conserved GP63 epitopes across species enable development of multi-species vaccines and diagnostics.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Leishmaniasis (general)", "glycan_involvement": "Glycosylation site differences may aid in species differentiation.", "mechanism": "GP63 sequence variation can be used for species identification and epidemiological studies.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Leishmaniasis (general)", "glycan_involvement": "Glycosylation may modulate protease activity and host interactions.", "mechanism": "GP63 protease activity enables parasite survival by protecting against host immune responses.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12140206" }, { "confidence": "medium", "disease": "Leishmaniasis (general)", "glycan_involvement": "N-glycosylation increases solubility and folding efficiency in expression systems.", "mechanism": "GP63 is a candidate for recombinant protein production for vaccines due to its hydrophilicity and glycosylation profile.", "protein": "GP63 (Leishmanolysin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140206" }, { "confidence": "high", "disease": "Statin-Induced Necrotizing Autoimmune Myopathy (SINAM)", "glycan_involvement": "HMG-CoA reductase is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Statin-induced upregulation of HMG-CoA reductase in muscle cells leads to autoantibody (anti-HMGCR) production, causing immune-mediated muscle necrosis.", "protein": "HMG-CoA Reductase", "relationship_type": "causal", "source_pmcid": "PMC12140385" }, { "confidence": "medium", "disease": "Statin-Induced Necrotizing Autoimmune Myopathy (SINAM)", "glycan_involvement": "SRP is a ribonucleoprotein complex; glycosylation may modulate immune response.", "mechanism": "Anti-SRP antibodies are tested as biomarkers for autoimmune myopathies, though negative in this case.", "protein": "Signal Recognition Particle (SRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12140385" }, { "confidence": "medium", "disease": "Myalgias", "glycan_involvement": "LDLR is heavily N-glycosylated, which is essential for its function and trafficking.", "mechanism": "Statins upregulate LDLR, altering cholesterol metabolism and potentially affecting muscle cell membrane composition.", "protein": "Low-Density Lipoprotein Receptor (LDLR)", "relationship_type": "causal", "source_pmcid": "PMC12140385" }, { "confidence": "high", "disease": "Statin-Induced Necrotizing Autoimmune Myopathy (SINAM)", "glycan_involvement": "IgG N-glycosylation modulates effector function and anti-inflammatory activity.", "mechanism": "IVIG (pooled IgG) is used therapeutically to modulate immune response in SINAM.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140385" }, { "confidence": "medium", "disease": "Statin-Induced Necrotizing Autoimmune Myopathy (SINAM)", "glycan_involvement": "ANA are glycoproteins; glycosylation may affect immunogenicity.", "mechanism": "ANA positivity indicates autoimmune activity, supporting diagnosis.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12140385" }, { "confidence": "high", "disease": "Diffuse Large B-Cell Lymphoma of the Common Bile Duct (DLBCL-CBD)", "glycan_involvement": "CD20 is a glycosylated membrane protein; glycosylation affects antibody binding and immune recognition.", "mechanism": "CD20 is expressed on malignant B cells and targeted by rituximab in R-CHOP therapy.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140684" }, { "confidence": "high", "disease": "Cholangiocarcinoma", "glycan_involvement": "CA19-9 is a sialylated glycan antigen (Sialyl-Lewis a) on glycoproteins.", "mechanism": "Elevated CA19-9 is used as a biomarker for cholangiocarcinoma but can be mildly elevated in DLBCL-CBD.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Diffuse Large B-Cell Lymphoma of the Common Bile Duct (DLBCL-CBD)", "glycan_involvement": "BCL2 is glycosylated; glycosylation may affect protein stability and apoptosis regulation.", "mechanism": "BCL2 expression is used in immunophenotyping to classify DLBCL subtype.", "protein": "BCL2", "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Diffuse Large B-Cell Lymphoma of the Common Bile Duct (DLBCL-CBD)", "glycan_involvement": "MUM1 is glycosylated; glycosylation may modulate transcriptional activity.", "mechanism": "MUM1 positivity helps define the non-germinal center B-cell-like subtype of DLBCL.", "protein": "MUM1 (IRF4)", "protein_enriched": { "function": "Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 com", "gene_name": "RAD9A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99638" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Diffuse Large B-Cell Lymphoma of the Common Bile Duct (DLBCL-CBD)", "glycan_involvement": "Ki-67 is a glycoprotein; glycosylation may affect nuclear localization and function.", "mechanism": "High Ki-67 index indicates high proliferative activity in DLBCL.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Obstructive Jaundice", "glycan_involvement": "Glycosylation of CD20 may influence cell adhesion and infiltration.", "mechanism": "CD20+ B-cell lymphoma infiltrates bile duct wall, causing stricture and jaundice.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Obstructive Jaundice", "glycan_involvement": "CA19-9 is a glycan epitope on glycoproteins, reflecting biliary tract inflammation.", "mechanism": "Mild elevation of CA19-9 observed in DLBCL-CBD presenting with jaundice.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Diffuse Large B-Cell Lymphoma of the Common Bile Duct (DLBCL-CBD)", "glycan_involvement": "PAX5 is glycosylated; glycosylation may affect nuclear transport and DNA binding.", "mechanism": "PAX5 positivity confirms B-cell lineage in DLBCL diagnosis.", "protein": "PAX5", "protein_enriched": { "function": "Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:10811620, PubMed:27181361). Fulfills a dual role by repressing B-lineage ina", "gene_name": "PAX5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02548" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140684" }, { "confidence": "medium", "disease": "Legionnaires\u2019 disease (Legionella pneumonia)", "glycan_involvement": "Glycosylation of MOMP is important for immune evasion and host cell interaction.", "mechanism": "MOMP mediates bacterial adhesion and invasion of host macrophages, initiating infection.", "protein": "Legionella pneumophila major outer membrane protein (MOMP)", "relationship_type": "causal", "source_pmcid": "PMC12140955" }, { "confidence": "high", "disease": "Legionnaires\u2019 disease (Legionella pneumonia)", "glycan_involvement": "O-antigen glycan structure is critical for serogroup specificity and immune recognition.", "mechanism": "LPS acts as a virulence factor, triggering host immune response and inflammation.", "protein": "Legionella pneumophila lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12140955" }, { "confidence": "medium", "disease": "Legionnaires\u2019 disease (Legionella pneumonia)", "glycan_involvement": "Glycosylation of surfactant proteins modulates pathogen binding.", "mechanism": "Surfactant proteins bind to Legionella surface glycans, enhancing clearance by macrophages.", "protein": "Human pulmonary surfactant proteins", "relationship_type": "protective", "source_pmcid": "PMC12140955" }, { "confidence": "low", "disease": "Legionnaires\u2019 disease (Legionella pneumonia)", "glycan_involvement": "Fc glycosylation affects antibody effector function.", "mechanism": "IgG mediates opsonization and clearance of Legionella.", "protein": "Human immunoglobulin G (IgG)", "relationship_type": "protective", "source_pmcid": "PMC12140955" }, { "confidence": "high", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "VEGF glycosylation affects receptor binding and vascular permeability.", "mechanism": "Anti-VEGF therapy (Bevacizumab) increases risk of PE, possibly via endothelial dysfunction and prothrombotic state.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "vWF glycosylation modulates multimerization and platelet binding.", "mechanism": "Glucocorticoids promote vWF synthesis/secretion, increasing coagulation and PE risk.", "protein": "Von Willebrand Factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "PAI-1 glycosylation affects stability and activity.", "mechanism": "Glucocorticoids increase PAI-1, inhibiting fibrinolysis and promoting thrombosis/PE.", "protein": "Plasminogen Activator Inhibitor-1 (PAI-1)", "protein_enriched": { "function": "Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it", "gene_name": "SERPINE1", "glycan_count": 16, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G07799LX", "G11870QZ", "G22310AV", "G26330YA", "G27058EU", "G45395BF", "G49955PK", "G51413EV", "G72791KH", "G84452RH", "G88374WZ", "G20706XG", "G92135MA", "G29068FM", "G43417UB", "G49108TO" ], "uniprot_id": "P05121" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "high", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "Glycosylation modulates receptor trafficking and hormone binding.", "mechanism": "Estrogen-containing drugs (NuvaRing) increase PE risk via procoagulant effects.", "protein": "Estrogen Receptor", "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "high", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "Glycosylation affects receptor stability and function.", "mechanism": "Progesterone-containing drugs (NuvaRing) increase PE risk via procoagulant effects.", "protein": "Progesterone Receptor", "protein_enriched": { "function": "The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform,", "gene_name": "PGR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06401" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "HER2 glycosylation influences antibody binding and immune response.", "mechanism": "Trastuzumab (anti-HER2) therapy linked to PE in breast cancer patients.", "protein": "HER2/ErbB2", "protein_enriched": { "function": "Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, althou", "gene_name": "ERBB2", "glycan_count": 29, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G52890YB", "G96577RX", "G43417UB", "G14972EH", "G16125XL", "G43223CG", "G45395BF", "G62765YT", "G64527OM", "G70101JE", "G80920RR", "G87661QW", "G05724UK", "G31852PQ", "G39188ZX", "G81315DD", "G00912UN", "G08290VR", "G08918WF", "G41071NU", "G44215PV", "G48414YA", "G65184UU", "G66163OV", "G83646BJ", "G95133RI", "G15169WU", "G09724ZC", "G46524LG" ], "uniprot_id": "P04626" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "PD-1 glycosylation modulates ligand binding and immune signaling.", "mechanism": "PD-1 inhibitors (Nivolumab, Keytruda) increase PE risk via immune activation and inflammation.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "CD20 glycosylation affects antibody-dependent cytotoxicity.", "mechanism": "Rituximab (anti-CD20) therapy associated with PE in autoimmune disease patients.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "high", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "JAK1 glycosylation may affect protein stability and signaling.", "mechanism": "JAK inhibitors (Baricitinib, Xeljanz) increase PE risk in IMID patients.", "protein": "Janus Kinase 1 (JAK1)", "protein_enriched": { "function": "Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive i", "gene_name": "JAK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60674" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "high", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "Glycosylation influences enzyme activity and drug interaction.", "mechanism": "Aromatase inhibitors (Letrozole) double PE risk in breast cancer patients.", "protein": "Aromatase (CYP19A1)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (P", "gene_name": "CYP19A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11511" }, "relationship_type": "causal", "source_pmcid": "PMC12140972" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation required for secretion and stability; glycosylation may affect protease binding.", "mechanism": "Elevated serum \u03b12-MG correlates with insulin resistance and hyperglycemia; modulates cytokine and protease activity.", "protein": "Alpha-2-macroglobulin (\u03b12-MG)", "protein_enriched": { "function": "Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different p", "gene_name": "A2M", "glycan_count": 172, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G02030ZB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06247RL", "G06356OH", "G07799LX", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G13131HA", "G14547CB", "G14972EH", "G14994KB", "G15038BD", "G15169WU", "G15664MX", "G20528HD", "G20706XG", "G22208HN", "G22310AV", "G22572EH", "G23294PN", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G28681TP", "G30221QT", "G30740WO", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G35541EV", "G36379GD", "G37509XX", "G37692EO", "G37868ZX", "G39619TI", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44215PV", "G44331JI", "G44753VC", "G45395BF", "G45504EY", "G45526EA", "G46503DX", "G46691LC", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G49755GI", "G51413EV", "G51640FO", "G51653BI", "G52358QA", "G52527GH", "G56518TU", "G57776ZS", "G57776ZU", "G59324HL", "G59626AS", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G67164EE", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72667IM", "G72747WU", "G75418YA", "G75983OB", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G81124ET", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83555HU", "G83646BJ", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G89045VA", "G90382BL", "G90659AW", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G92551JA", "G93718GY", "G94470IW", "G94917XT", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G78790NZ", "G29068FM", "G22573RC", "G23863VK", "G85740DB", "G91636VS", "G01650EU", "G02815KT", "G06110VR", "G15486FH", "G31916IQ", "G33609NS", "G34730YF", "G37399XV", "G39446WN", "G50045TK", "G67324HN", "G82119TF", "G82463GQ", "G05933EN", "G47737VJ", "G64751KD", "G43417UB", "G28541PG", "G39188ZX", "G47448YK", "G72291OX", "G72735IY", "G72787SB", "G83204BU", "G84349RE", "G49108TO" ], "uniprot_id": "P01023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation essential for plasma function.", "mechanism": "Serum \u03b12-MG is upregulated in obesity, reflecting acute-phase response and metabolic imbalance.", "protein": "Alpha-2-macroglobulin (\u03b12-MG)", "protein_enriched": { "function": "Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different p", "gene_name": "A2M", "glycan_count": 172, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G02030ZB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06247RL", "G06356OH", "G07799LX", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G13131HA", "G14547CB", "G14972EH", "G14994KB", "G15038BD", "G15169WU", "G15664MX", "G20528HD", "G20706XG", "G22208HN", "G22310AV", "G22572EH", "G23294PN", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G28681TP", "G30221QT", "G30740WO", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G35541EV", "G36379GD", "G37509XX", "G37692EO", "G37868ZX", "G39619TI", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44215PV", "G44331JI", "G44753VC", "G45395BF", "G45504EY", "G45526EA", "G46503DX", "G46691LC", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G49755GI", "G51413EV", "G51640FO", "G51653BI", "G52358QA", "G52527GH", "G56518TU", "G57776ZS", "G57776ZU", "G59324HL", "G59626AS", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G67164EE", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72667IM", "G72747WU", "G75418YA", "G75983OB", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G81124ET", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83555HU", "G83646BJ", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G89045VA", "G90382BL", "G90659AW", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G92551JA", "G93718GY", "G94470IW", "G94917XT", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G78790NZ", "G29068FM", "G22573RC", "G23863VK", "G85740DB", "G91636VS", "G01650EU", "G02815KT", "G06110VR", "G15486FH", "G31916IQ", "G33609NS", "G34730YF", "G37399XV", "G39446WN", "G50045TK", "G67324HN", "G82119TF", "G82463GQ", "G05933EN", "G47737VJ", "G64751KD", "G43417UB", "G28541PG", "G39188ZX", "G47448YK", "G72291OX", "G72735IY", "G72787SB", "G83204BU", "G84349RE", "G49108TO" ], "uniprot_id": "P01023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "N-glycosylation may affect renal clearance and biomarker utility.", "mechanism": "Serum \u03b12-MG increases with albuminuria and progression of nephropathy.", "protein": "Alpha-2-macroglobulin (\u03b12-MG)", "protein_enriched": { "function": "Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different p", "gene_name": "A2M", "glycan_count": 172, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G02030ZB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06247RL", "G06356OH", "G07799LX", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G13131HA", "G14547CB", "G14972EH", "G14994KB", "G15038BD", "G15169WU", "G15664MX", "G20528HD", "G20706XG", "G22208HN", "G22310AV", "G22572EH", "G23294PN", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G28681TP", "G30221QT", "G30740WO", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G35541EV", "G36379GD", "G37509XX", "G37692EO", "G37868ZX", "G39619TI", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44215PV", "G44331JI", "G44753VC", "G45395BF", "G45504EY", "G45526EA", "G46503DX", "G46691LC", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G49755GI", "G51413EV", "G51640FO", "G51653BI", "G52358QA", "G52527GH", "G56518TU", "G57776ZS", "G57776ZU", "G59324HL", "G59626AS", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G67164EE", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72667IM", "G72747WU", "G75418YA", "G75983OB", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G81124ET", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83555HU", "G83646BJ", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G89045VA", "G90382BL", "G90659AW", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G92551JA", "G93718GY", "G94470IW", "G94917XT", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G78790NZ", "G29068FM", "G22573RC", "G23863VK", "G85740DB", "G91636VS", "G01650EU", "G02815KT", "G06110VR", "G15486FH", "G31916IQ", "G33609NS", "G34730YF", "G37399XV", "G39446WN", "G50045TK", "G67324HN", "G82119TF", "G82463GQ", "G05933EN", "G47737VJ", "G64751KD", "G43417UB", "G28541PG", "G39188ZX", "G47448YK", "G72291OX", "G72735IY", "G72787SB", "G83204BU", "G84349RE", "G49108TO" ], "uniprot_id": "P01023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation required for plasma stability.", "mechanism": "Elevated \u03b12-MG correlates with retinopathy severity and HbA1c.", "protein": "Alpha-2-macroglobulin (\u03b12-MG)", "protein_enriched": { "function": "Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different p", "gene_name": "A2M", "glycan_count": 172, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G02030ZB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06247RL", "G06356OH", "G07799LX", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G13131HA", "G14547CB", "G14972EH", "G14994KB", "G15038BD", "G15169WU", "G15664MX", "G20528HD", "G20706XG", "G22208HN", "G22310AV", "G22572EH", "G23294PN", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G28681TP", "G30221QT", "G30740WO", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G35541EV", "G36379GD", "G37509XX", "G37692EO", "G37868ZX", "G39619TI", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44215PV", "G44331JI", "G44753VC", "G45395BF", "G45504EY", "G45526EA", "G46503DX", "G46691LC", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G49755GI", "G51413EV", "G51640FO", "G51653BI", "G52358QA", "G52527GH", "G56518TU", "G57776ZS", "G57776ZU", "G59324HL", "G59626AS", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G67164EE", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72667IM", "G72747WU", "G75418YA", "G75983OB", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G81124ET", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83555HU", "G83646BJ", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G89045VA", "G90382BL", "G90659AW", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G92551JA", "G93718GY", "G94470IW", "G94917XT", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G78790NZ", "G29068FM", "G22573RC", "G23863VK", "G85740DB", "G91636VS", "G01650EU", "G02815KT", "G06110VR", "G15486FH", "G31916IQ", "G33609NS", "G34730YF", "G37399XV", "G39446WN", "G50045TK", "G67324HN", "G82119TF", "G82463GQ", "G05933EN", "G47737VJ", "G64751KD", "G43417UB", "G28541PG", "G39188ZX", "G47448YK", "G72291OX", "G72735IY", "G72787SB", "G83204BU", "G84349RE", "G49108TO" ], "uniprot_id": "P01023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation affects anti-protease activity and plasma half-life.", "mechanism": "Reduced serum AAT in T2DM; imbalance with neutrophil elastase may promote inflammation and metabolic dysfunction.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates anti-inflammatory function.", "mechanism": "Lower AAT in obesity compared to controls; may reflect subclinical inflammation.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation required for complement activation and stability.", "mechanism": "Elevated C3 in T2DM; promotes adipocyte dysfunction, inflammation, and \u03b2-cell apoptosis.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation essential for function.", "mechanism": "C3 upregulated in obesity; reflects chronic low-grade inflammation and insulin resistance.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects adipokine activity.", "mechanism": "Serum ZAG is reduced in obesity; involved in lipid mobilization and insulin sensitivity.", "protein": "Zinc-\u03b12-glycoprotein (ZAG)", "protein_enriched": { "function": "Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids", "gene_name": "AZGP1", "glycan_count": 201, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G01485JJ", "G02628JF", "G02815KT", "G04854VP", "G05049YU", "G06247RL", "G06356OH", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G14260UH", "G14972EH", "G15169WU", "G17208MA", "G20312EM", "G20706XG", "G22310AV", "G23719VF", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27947YN", "G28681TP", "G31852PQ", "G33416PL", "G33791AF", "G35029YA", "G36379GD", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42962KI", "G43223CG", "G43669FQ", "G43734MM", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46524LG", "G46687AB", "G46902YN", "G47448YK", "G47518TP", "G47644PP", "G48414YA", "G50045TK", "G50427EO", "G51413EV", "G52527GH", "G54010QB", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64162JC", "G64527OM", "G66163OV", "G70101JE", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G72787SB", "G72791KH", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G79286RS", "G80333GO", "G81198YO", "G82463GQ", "G83229XP", "G84452RH", "G85144OK", "G85269DF", "G86234IN", "G86795LJ", "G88374WZ", "G88891KO", "G90575OW", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95865ZB", "G98129XB", "G00395TQ", "G23863VK", "G31685JQ", "G31916IQ", "G42358LZ", "G47737VJ", "G57818FI", "G70894RY", "G74724QE", "G77582RK", "G82348BZ", "G96577RX", "G02030ZB", "G03382KH", "G03930BU", "G05724UK", "G05933EN", "G06110VR", "G07246CJ", "G07755XJ", "G10256JP", "G10773YW", "G10819WX", "G11870QZ", "G12313PD", "G12579WK", "G14994KB", "G16175ZV", "G18647XP", "G20210JR", "G22572EH", "G22625SJ", "G23294PN", "G25418HZ", "G27126ED", "G29880MM", "G31544HA", "G34617SM", "G40664HB", "G41071NU", "G42124LM", "G46691LC", "G47012YE", "G49874UX", "G51640FO", "G54612UD", "G55383ZG", "G60177UT", "G60923RB", "G62894KT", "G63381RX", "G64409MC", "G65019XG", "G65184UU", "G66760KM", "G70418MS", "G70822IO", "G72735IY", "G72797UR", "G74430RZ", "G78790NZ", "G80223IX", "G80920RR", "G81263BG", "G82020ZR", "G82119TF", "G82830MN", "G83460ZZ", "G83646BJ", "G84820NF", "G86182NS", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G90093AU", "G91473PK", "G92062TF", "G94854LT", "G95133RI", "G95977AE", "G96091TT", "G98611JV", "G39213VZ", "G90725ZC", "G96957PS", "G49108TO" ], "uniprot_id": "P25311" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation modulates metabolic function.", "mechanism": "Lower ZAG in T2DM; may be linked to impaired glucose metabolism and diabetic nephropathy.", "protein": "Zinc-\u03b12-glycoprotein (ZAG)", "protein_enriched": { "function": "Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids", "gene_name": "AZGP1", "glycan_count": 201, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G01485JJ", "G02628JF", "G02815KT", "G04854VP", "G05049YU", "G06247RL", "G06356OH", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G14260UH", "G14972EH", "G15169WU", "G17208MA", "G20312EM", "G20706XG", "G22310AV", "G23719VF", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27947YN", "G28681TP", "G31852PQ", "G33416PL", "G33791AF", "G35029YA", "G36379GD", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42962KI", "G43223CG", "G43669FQ", "G43734MM", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46524LG", "G46687AB", "G46902YN", "G47448YK", "G47518TP", "G47644PP", "G48414YA", "G50045TK", "G50427EO", "G51413EV", "G52527GH", "G54010QB", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64162JC", "G64527OM", "G66163OV", "G70101JE", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G72787SB", "G72791KH", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G79286RS", "G80333GO", "G81198YO", "G82463GQ", "G83229XP", "G84452RH", "G85144OK", "G85269DF", "G86234IN", "G86795LJ", "G88374WZ", "G88891KO", "G90575OW", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95865ZB", "G98129XB", "G00395TQ", "G23863VK", "G31685JQ", "G31916IQ", "G42358LZ", "G47737VJ", "G57818FI", "G70894RY", "G74724QE", "G77582RK", "G82348BZ", "G96577RX", "G02030ZB", "G03382KH", "G03930BU", "G05724UK", "G05933EN", "G06110VR", "G07246CJ", "G07755XJ", "G10256JP", "G10773YW", "G10819WX", "G11870QZ", "G12313PD", "G12579WK", "G14994KB", "G16175ZV", "G18647XP", "G20210JR", "G22572EH", "G22625SJ", "G23294PN", "G25418HZ", "G27126ED", "G29880MM", "G31544HA", "G34617SM", "G40664HB", "G41071NU", "G42124LM", "G46691LC", "G47012YE", "G49874UX", "G51640FO", "G54612UD", "G55383ZG", "G60177UT", "G60923RB", "G62894KT", "G63381RX", "G64409MC", "G65019XG", "G65184UU", "G66760KM", "G70418MS", "G70822IO", "G72735IY", "G72797UR", "G74430RZ", "G78790NZ", "G80223IX", "G80920RR", "G81263BG", "G82020ZR", "G82119TF", "G82830MN", "G83460ZZ", "G83646BJ", "G84820NF", "G86182NS", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G90093AU", "G91473PK", "G92062TF", "G94854LT", "G95133RI", "G95977AE", "G96091TT", "G98611JV", "G39213VZ", "G90725ZC", "G96957PS", "G49108TO" ], "uniprot_id": "P25311" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140998" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, which modulates immune evasion and receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12141072" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation of spike protein may affect immunogenicity of Tfh epitope.", "mechanism": "Spike-derived Tfh epitope used as carrier in peptide vaccine to induce anti-Ang II antibodies, suppressing hypertension in mice.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141072" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Angiotensinogen (precursor) is a glycoprotein; glycosylation affects its stability and processing to Ang II.", "mechanism": "Ang II increases blood pressure via AT1R signaling, causing vasoconstriction and fluid retention.", "protein": "Angiotensin II", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141072" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation shields epitopes, influencing vaccine design and antibody responses.", "mechanism": "Spike protein is the main antigen in COVID-19 vaccines, inducing protective immunity.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141072" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect Tfh epitope presentation and immune priming.", "mechanism": "Priming with spike protein enhances Tfh epitope-Ang II vaccine efficacy, increasing anti-Ang II antibody titers and antihypertensive effect.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12141072" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation of angiotensinogen modulates its secretion and conversion to Ang II.", "mechanism": "Angiotensinogen is cleaved to Ang II, driving hypertension.", "protein": "Angiotensinogen", "relationship_type": "causal", "source_pmcid": "PMC12141072" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects detection by antibodies and diagnostic assays.", "mechanism": "Spike protein presence indicates SARS-CoV-2 infection.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12141072" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may influence T cell epitope processing and presentation.", "mechanism": "Spike-derived Tfh epitope activates Tfh cells, facilitating antibody production against Ang II.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141072" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Indirect; glycosylation of precursor angiotensinogen affects Ang II levels.", "mechanism": "Anti-Ang II antibodies induced by vaccine neutralize Ang II, lowering blood pressure.", "protein": "Angiotensin II", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141072" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates immunogenicity and antibody accessibility.", "mechanism": "Vaccination with spike protein induces Tfh cell activation and robust antibody responses.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12141072" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation of dystroglycan is essential for its function; loss or alteration impairs DGC assembly.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex (DGC), impairing dystroglycan function and muscle membrane stability.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12141486" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycoproteins in the DGC; its absence disrupts glycoprotein-mediated membrane integrity.", "mechanism": "Mutations in DMD gene cause loss of dystrophin, destabilizing the DGC and leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Sarcoglycans are glycosylated; proper glycosylation is required for DGC assembly.", "mechanism": "Downregulation of sarcoglycans in DMD satellite cells impairs DGC function and muscle stability.", "protein": "Sarcoglycans", "relationship_type": "causal", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation status affects sarcospan's membrane localization and function.", "mechanism": "Reduced sarcospan expression in DMD satellite cells contributes to DGC instability.", "protein": "Sarcospan", "relationship_type": "causal", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation may modulate syntrophin interactions within the DGC.", "mechanism": "Sntb2 is upregulated in DMD satellite cells, possibly as a compensatory response to DGC disruption.", "protein": "Syntrophin (Sntb2)", "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Collagen glycosylation affects fibril formation and tissue stiffness.", "mechanism": "Upregulated in DMD satellite cells, indicating increased extracellular matrix remodeling and fibrosis.", "protein": "Collagen type I (Col1a1/Col1a2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Fibronectin glycosylation modulates cell adhesion and matrix assembly.", "mechanism": "Elevated in DMD satellite cells, reflecting altered ECM composition and impaired regeneration.", "protein": "Fibronectin (Fn1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation influences periostin's ECM interactions.", "mechanism": "Upregulated in DMD-enriched satellite cell cluster, associated with fibrosis and impaired regeneration.", "protein": "Periostin (Postn)", "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Heparan sulfate glycosylation is critical for Sdc1 function in cell signaling.", "mechanism": "Increased Sdc1 expression in DMD satellite cells, linked to altered cell-matrix signaling.", "protein": "Syndecan-1 (Sdc1)", "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Hyaluronan and other glycan modifications regulate CD44-mediated signaling.", "mechanism": "Altered expression in DMD satellite cells, affecting cell adhesion and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141486" }, { "confidence": "high", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects its stability and renal filtration.", "mechanism": "Elevated urinary albumin (albuminuria) is a key biomarker for DKD progression and renal damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation may influence albumin's renal handling and excretion.", "mechanism": "Persistent albuminuria is diagnostic for diabetic nephropathy and reflects glomerular injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation status can affect albumin's filtration and reabsorption.", "mechanism": "Albuminuria is a marker of CKD severity and progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "medium", "disease": "End-Stage Renal Disease", "glycan_involvement": "Altered glycosylation may exacerbate renal loss of albumin.", "mechanism": "High albuminuria predicts progression to ESRD in diabetic patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate albumin's vascular interactions.", "mechanism": "Albuminuria is associated with hypertensive nephrosclerosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Hyperglycemia can alter albumin glycosylation, affecting renal filtration.", "mechanism": "Microalbuminuria is an early indicator of renal complications in T2DM.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Therapeutic interventions may indirectly affect glycosylation via improved glycemic control.", "mechanism": "Reduction of albuminuria is a therapeutic goal; spironolactone reduces albuminuria.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Improved renal function may normalize albumin glycosylation patterns.", "mechanism": "Spironolactone and RAAS blockers reduce albuminuria, improving renal outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141752" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Reduced albumin loss may preserve normal glycosylation status.", "mechanism": "Lowering albuminuria via spironolactone is protective against DKD progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12141752" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Aberrant glycosylation may enhance albumin's pro-inflammatory effects.", "mechanism": "Persistent albuminuria contributes to renal inflammation and fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12141752" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Ozoralizumab is a glycoprotein-based therapeutic; glycosylation may affect immunogenicity and BBB penetration.", "mechanism": "Ozoralizumab, a TNF-\u03b1 inhibitor NANOBODY\u00ae, may induce demyelinating lesions in the optic nerve as a side effect.", "protein": "Ozoralizumab", "relationship_type": "causal", "source_pmcid": "PMC12141823" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation may modulate its activity and receptor binding.", "mechanism": "TNF-\u03b1 is targeted by inhibitors (including ozoralizumab) to treat RA.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141823" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation of TNF-\u03b1 may influence immune response and drug interaction.", "mechanism": "Inhibition of TNF-\u03b1 can rarely trigger demyelinating events including optic neuritis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141823" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and antibody binding.", "mechanism": "Presence of this autoantibody is a biomarker for some forms of optic neuritis.", "protein": "Anti-myelin oligodendrocyte glycoprotein antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12141823" }, { "confidence": "medium", "disease": "Neuromyelitis optica (NMO)", "glycan_involvement": "Aquaporin 4 glycosylation may influence antibody recognition.", "mechanism": "Autoantibody is a diagnostic marker for NMO, which can present with optic neuritis.", "protein": "Anti-aquaporin 4 antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12141823" }, { "confidence": "low", "disease": "Optic neuritis", "glycan_involvement": "Albumin glycosylation can affect drug binding and pharmacokinetics.", "mechanism": "Ozoralizumab's albumin-binding property may limit its cumulative effect and restrict lesion extent.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12141823" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation of peptides may affect antibody recognition.", "mechanism": "Elevated levels are diagnostic for RA.", "protein": "Anti-cyclic citrullinated peptide antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12141823" }, { "confidence": "medium", "disease": "Demyelinating CNS disease", "glycan_involvement": "Glycosylation may facilitate BBB crossing and tissue penetration.", "mechanism": "Ozoralizumab may cross the BBB and induce demyelinating lesions more readily than conventional TNF-\u03b1 inhibitors.", "protein": "Ozoralizumab", "relationship_type": "causal", "source_pmcid": "PMC12141823" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may modulate TNF-\u03b1's immunological effects.", "mechanism": "TNF-\u03b1 inhibitors may rarely trigger or worsen demyelinating diseases like MS.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141823" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects drug stability, immunogenicity, and efficacy.", "mechanism": "Ozoralizumab is used to treat RA by inhibiting TNF-\u03b1.", "protein": "Ozoralizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141823" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation affects cell adhesion and tumor invasiveness.", "mechanism": "CD56 is expressed on SCLC cells and used for diagnosis.", "protein": "CD56", "relationship_type": "biomarker", "source_pmcid": "PMC12141988" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation may affect protein stability and localization.", "mechanism": "TTF-1 positivity helps identify SCLC origin.", "protein": "TTF-1", "relationship_type": "biomarker", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation modulates secretion and immune recognition.", "mechanism": "Chromogranin A is partially positive in SCLC, indicating neuroendocrine differentiation.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation influences membrane localization.", "mechanism": "Synaptophysin positivity supports neuroendocrine tumor diagnosis.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141988" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 inhibitors (durvalumab, atezolizumab) prolong survival in SCLC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141988" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "PD-1 inhibitors (nivolumab) used in combination therapy for SCLC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Potential glycosylation may affect enzyme activity.", "mechanism": "PARP inhibitors block DNA repair, enhancing cytotoxicity of TMZ.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation may influence DNA repair function.", "mechanism": "ERCC1 deficiency sensitizes tumors to immunotherapy via STING pathway.", "protein": "ERCC1", "relationship_type": "biomarker", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation affects chemokine secretion and receptor binding.", "mechanism": "CXCL10 production recruits CD8+ T cells, enhancing anti-tumor immunity.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "protective", "source_pmcid": "PMC12141988" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "CCL5 promotes immune cell infiltration and anti-tumor response.", "protein": "CCL5", "relationship_type": "protective", "source_pmcid": "PMC12141988" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Autoantibodies against \u03b22-glycoprotein-I are associated with antiphospholipid syndrome and SLE.", "protein": "\u03b22-glycoprotein-I", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Potential glycosylation modulates protein-protein interactions.", "mechanism": "Genetic susceptibility locus for psoriasis and SLE; involved in immune signaling.", "protein": "TRAF3IP2", "relationship_type": "causal", "source_pmcid": "PMC12142130" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation may affect STAT4 stability and function.", "mechanism": "Genetic variant increases risk for SLE and psoriasis via cytokine signaling.", "protein": "STAT4", "relationship_type": "causal", "source_pmcid": "PMC12142130" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation may regulate phosphatase activity.", "mechanism": "Genetic variant associated with increased risk for SLE and psoriasis.", "protein": "PTPN22", "relationship_type": "causal", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation influences autoantigenicity.", "mechanism": "Anti-U1-RNP antibodies are frequent in SLE and comorbid psoriasis.", "protein": "U1-RNP", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Anti-SSA antibodies are common in SLE and comorbid psoriasis.", "protein": "SSA/Ro52 and SSA/Ro60", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigen presentation.", "mechanism": "Anti-SSB antibodies are frequent in SLE and comorbid psoriasis.", "protein": "SSB/La", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation impacts antigenicity.", "mechanism": "Autoantibodies to cardiolipin-binding glycoproteins are associated with SLE and APS.", "protein": "Cardiolipin-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation is essential for complement activation.", "mechanism": "Low C3 levels indicate disease activity in SLE.", "protein": "C3 complement", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation required for complement function.", "mechanism": "Low C4 levels are associated with active SLE.", "protein": "C4 complement", "relationship_type": "biomarker", "source_pmcid": "PMC12142130" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Pgp is a glycoprotein; glycosylation is essential for its stability and trafficking to the plasma membrane.", "mechanism": "P-glycoprotein (Pgp) mediates drug efflux, reducing intracellular 5-Fu concentration and promoting chemoresistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12142228" }, { "confidence": "high", "disease": "5-fluorouracil-resistant colorectal cancer", "glycan_involvement": "Glycosylation of Pgp is required for its function in drug resistance.", "mechanism": "Upregulated Pgp expression is associated with 5-Fu resistance in CRC tissues and cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142228" }, { "confidence": "medium", "disease": "5-fluorouracil-resistant colorectal cancer", "glycan_involvement": "Targeting glycosylation may affect Pgp function and drug resistance.", "mechanism": "Targeting Pgp can restore 5-Fu sensitivity in resistant CRC cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142228" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CEA is a heavily glycosylated protein; glycosylation is essential for its secretion and detection.", "mechanism": "Elevated serum CEA correlates with tumor burden and poor prognosis.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "high", "disease": "Metastatic colorectal cancer", "glycan_involvement": "Glycosylation enables CEA's stability and immunogenicity as a serum marker.", "mechanism": "High baseline CEA is associated with worse overall survival.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "CA 19-9 is a sialylated Lewis antigen (glycan epitope) on glycoproteins/lipids.", "mechanism": "Elevated CA 19-9 is associated with advanced disease and poor prognosis.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "medium", "disease": "Metastatic colorectal cancer", "glycan_involvement": "CA 19-9 is a glycan structure; its expression depends on glycosyltransferase activity.", "mechanism": "High CA 19-9 levels correlate with worse survival outcomes.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycan epitope recognized by specific antibodies.", "mechanism": "CA 19-9 is frequently elevated and used for disease monitoring.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "medium", "disease": "Gastrointestinal cancers", "glycan_involvement": "Glycan structure present on multiple glycoproteins/lipids.", "mechanism": "CA 19-9 can be elevated in various GI cancers.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "medium", "disease": "Gastrointestinal cancers", "glycan_involvement": "Glycosylation is required for CEA's function and detection.", "mechanism": "CEA is expressed in various epithelial tumors of GI origin.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "CEA is used as a target in some immunotherapies and for monitoring recurrence.", "protein": "Carcinoembryonic antigen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142231" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Both markers are glycosylated; glycan structures are essential for their serum detection.", "mechanism": "Combined with CA 19-9 as a Tumor Marker Index (TMI), improves prognostic accuracy for survival.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CA 19-9 is a glycan epitope; glycosylation is central to its function as a marker.", "mechanism": "Combined with CEA as TMI, high TMI independently predicts poor overall survival in metastatic CRC.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12142231" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "PAPP-A is a glycoprotein; glycosylation is essential for its stability and secretion.", "mechanism": "Low maternal PAPP-A levels in first trimester are associated with increased risk of developing GDM; PAPP-A regulates IGF bioavailability, impacting glucose metabolism.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Glycosylation affects PAPP-A's function in placental development.", "mechanism": "Low PAPP-A levels linked to increased risk of pre-eclampsia, possibly via impaired placentation and reduced IGF activity.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Fetal Growth Restriction", "glycan_involvement": "Glycosylation modulates PAPP-A's proteolytic activity.", "mechanism": "Low PAPP-A impairs IGF-mediated trophoblast invasion, leading to placental insufficiency and fetal growth restriction.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Placental Insufficiency", "glycan_involvement": "Glycosylation required for PAPP-A secretion and function.", "mechanism": "Low PAPP-A reduces IGF bioavailability, impairing placental vascularization and nutrient delivery.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "causal", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Neonatal Hypoglycemia", "glycan_involvement": "Glycosylation maintains PAPP-A stability in circulation.", "mechanism": "Low PAPP-A in mothers with GDM is associated with increased risk of neonatal hypoglycemia due to fetal hyperinsulinemia.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Fetal Macrosomia", "glycan_involvement": "Glycosylation influences PAPP-A's interaction with IGF-binding proteins.", "mechanism": "Low PAPP-A in GDM pregnancies correlates with increased risk of fetal macrosomia via altered IGF signaling.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "low", "disease": "Subclinical Myocardial Dysfunction in Offspring", "glycan_involvement": "Glycosylation affects PAPP-A's bioactivity in placental tissue.", "mechanism": "Low maternal PAPP-A in GDM may contribute to fetal cardiac remodeling and dysfunction via placental and metabolic stress.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "\u03b2-hCG is heavily glycosylated; glycan structures affect its half-life and receptor interactions.", "mechanism": "Lower first-trimester \u03b2-hCG levels are associated with increased GDM risk, possibly reflecting placental dysfunction.", "protein": "Free \u03b2-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation status may affect assay sensitivity and specificity.", "mechanism": "Potential for PAPP-A to be used in multivariable prediction models for early intervention in GDM.", "protein": "Pregnancy-Associated Plasma Protein-A (PAPP-A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142282" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "IGFs are glycoproteins; glycosylation modulates receptor binding and activity.", "mechanism": "PAPP-A regulates IGF bioavailability; altered IGF signaling contributes to GDM pathophysiology.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "causal", "source_pmcid": "PMC12142282" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "N-glycosylation is required for CFTR folding, trafficking, and function.", "mechanism": "Nonsense mutations in CFTR lead to truncated, nonfunctional glycoprotein, causing defective chloride transport.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation is essential for secretion and stability of Factor VIII.", "mechanism": "Nonsense mutations in F8 gene result in loss of glycosylated Factor VIII, impairing coagulation.", "protein": "Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "N-glycosylation affects secretion and activity of Factor IX.", "mechanism": "Nonsense mutations in F9 gene cause loss of glycosylated Factor IX, leading to bleeding disorder.", "protein": "Factor IX", "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Fabry disease", "glycan_involvement": "N-glycosylation is critical for lysosomal targeting and enzyme stability.", "mechanism": "Nonsense mutations in GLA gene result in deficient lysosomal glycoprotein, causing glycosphingolipid accumulation.", "protein": "\u03b1-galactosidase A (GLA)", "protein_enriched": { "function": "Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome", "gene_name": "GLA", "glycan_count": 51, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11870QZ", "G12313PD", "G15169WU", "G23719VF", "G26295XE", "G28681TP", "G31852PQ", "G34989PA", "G37412TK", "G41247ZX", "G42466VF", "G43669FQ", "G45395BF", "G47012YE", "G47644PP", "G48414YA", "G62765YT", "G62894KT", "G70101JE", "G70232NH", "G72291OX", "G74724QE", "G75983OB", "G76417NN", "G80920RR", "G81315DD", "G82463GQ", "G83460ZZ", "G90382BL", "G92275SC", "G01937VC", "G05724UK", "G06110VR", "G14669DU", "G22768VO", "G23294PN", "G39188ZX", "G56014GC", "G71469XA", "G00406II", "G17689EW", "G27058EU", "G29184RN", "G46503DX", "G50282JC", "G90575OW", "G95995BI", "G96091TT", "G49108TO" ], "uniprot_id": "P06280" }, "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "medium", "disease": "Choroideremia", "glycan_involvement": "Glycosylation status not specified, but REP1 is a glycoprotein.", "mechanism": "Nonsense mutations in CHM gene cause REP1 deficiency, impairing Rab protein prenylation and retinal cell survival.", "protein": "Rab escort protein 1 (REP1)", "protein_enriched": { "function": "Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaf", "gene_name": "PSTPIP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43586" }, "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Usher syndrome", "glycan_involvement": "N-glycosylation is important for usherin structure and function.", "mechanism": "Nonsense mutations in USH2A gene lead to truncated usherin, disrupting auditory and retinal cell function.", "protein": "Usherin (USH2A)", "protein_enriched": { "function": "Involved in hearing and vision as member of the USH2 complex. In the inner ear, required for the maintenance of the hair bundle ankle formation, which connects growing stereocilia in developing cochle", "gene_name": "USH2A", "glycan_count": 2, "glycosylation_sites_count": 66, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O75445" }, "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Congenital hypomyelination", "glycan_involvement": "N-glycosylation is required for MPZ adhesion and myelin compaction.", "mechanism": "Nonsense mutation (P0Q215X) in MPZ gene produces truncated glycoprotein, causing myelination defects.", "protein": "Myelin protein zero (MPZ)", "protein_enriched": { "function": "Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction", "gene_name": "MPZ", "glycan_count": 15, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G10773YW", "G19385TO", "G20210JR", "G23294PN", "G23984SE", "G25451PN", "G31916IQ", "G47012YE", "G60177UT", "G62894KT", "G82119TF", "G82830MN", "G84820NF", "G92062TF", "G99966GV" ], "uniprot_id": "P25189" }, "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "medium", "disease": "Charcot\u2013Marie\u2013Tooth disease", "glycan_involvement": "N-glycosylation is important for neprilysin stability and function.", "mechanism": "Nonsense mutation (Q522X) in MME gene leads to loss of glycoprotein neprilysin, affecting peptide degradation in nerves.", "protein": "Neprilysin (MME)", "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "medium", "disease": "Shwachman-Diamond syndrome", "glycan_involvement": "Glycosylation not specified; possible but not confirmed.", "mechanism": "Nonsense mutations in SBDS gene cause loss of ribosome maturation factor, impairing protein synthesis.", "protein": "SBDS", "protein_enriched": { "function": "Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating riboso", "gene_name": "SBDS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3A5" }, "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Li-Fraumeni syndrome", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Nonsense mutations in TP53 gene result in loss of tumor suppressor function, increasing cancer risk.", "protein": "p53 (TP53)", "relationship_type": "causal", "source_pmcid": "PMC12142302" }, { "confidence": "high", "disease": "Pyknodysostosis", "glycan_involvement": "Cathepsin K is a glycoprotein; glycosylation is required for its proper folding, stability, and lysosomal targeting.", "mechanism": "Loss-of-function mutations in Cathepsin K impair osteoclast-mediated bone resorption, leading to osteosclerosis and skeletal abnormalities.", "protein": "Cathepsin K", "protein_enriched": { "function": "Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play ", "gene_name": "CTSK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P43235" }, "relationship_type": "causal", "source_pmcid": "PMC12142366" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycosylation of GP is critical for immune evasion and host cell attachment.", "mechanism": "GP mediates viral entry into host cells and is essential for infection and pathogenesis.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12142521" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycan shield on GP affects antibody accessibility and vaccine design.", "mechanism": "GP is targeted by vaccine candidates and therapeutic antibodies to block viral entry.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142521" }, { "confidence": "high", "disease": "Major bleeding", "glycan_involvement": "Shedding alters glycosylation status, affecting platelet clearance.", "mechanism": "ECMO induces shear force-mediated shedding of glycoprotein Ib\u03b1, leading to thrombocytopenia and increased bleeding risk.", "protein": "Glycoprotein Ib\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12142538" }, { "confidence": "high", "disease": "Blood loss anemia", "glycan_involvement": "Glycosylation loss accelerates platelet removal.", "mechanism": "Loss of glycoprotein Ib\u03b1 on platelets during ECMO increases platelet clearance, contributing to anemia.", "protein": "Glycoprotein Ib\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Altered glycosylation may affect fibrinogen function.", "mechanism": "ECMO-induced liver dysfunction alters fibrinogen levels, contributing to DIC and bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Major bleeding", "glycan_involvement": "Glycosylation changes impact coagulation activity.", "mechanism": "ECMO-induced liver dysfunction disrupts prothrombin synthesis and glycosylation, increasing bleeding risk.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142538" }, { "confidence": "high", "disease": "Major bleeding", "glycan_involvement": "Shedding affects glycan-mediated platelet survival.", "mechanism": "ECMO causes time-dependent drop in platelet count via glycoprotein shedding, increasing bleeding.", "protein": "Platelet glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Blood loss anemia", "glycan_involvement": "Glycosylation status modulates fibrinogen function.", "mechanism": "Abnormal fibrinogen levels during ECMO contribute to anemia via impaired clot formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Loss of glycosylation promotes platelet dysfunction.", "mechanism": "Shedding of glycoprotein Ib\u03b1 during ECMO predisposes to DIC.", "protein": "Glycoprotein Ib\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Major bleeding", "glycan_involvement": "Glycosylation changes affect factor activity.", "mechanism": "ECMO alters APTT factor levels via liver dysfunction, increasing bleeding risk.", "protein": "Activated partial thromboplastin time (APTT) factors", "relationship_type": "biomarker", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycan loss accelerates platelet clearance, worsening hypovolemia.", "mechanism": "ECMO-induced bleeding and hypovolemia via platelet glycoprotein loss contribute to AKI.", "protein": "Platelet glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC12142538" }, { "confidence": "medium", "disease": "Acute liver injury (ALI)", "glycan_involvement": "Glycosylation changes reflect hepatic synthetic function.", "mechanism": "ECMO-induced liver dysfunction alters fibrinogen glycosylation, serving as a marker for ALI.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142538" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation supports cell-surface localization and stability, enabling its detection and function as a biomarker.", "mechanism": "TROP-2 overexpression correlates with larger tumor size, advanced nodal involvement, reduced overall and disease-free survival.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation facilitates antibody recognition and binding for targeted therapy.", "mechanism": "Targeting TROP-2 with antibody-drug conjugates (e.g., sacituzumab govitecan) delivers cytotoxic agents to TROP-2+ tumor cells.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142858" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation is essential for proper folding and membrane trafficking, enabling signaling.", "mechanism": "TROP-2 activates PI3K/AKT, ERK/MAPK, and NF-\u03baB pathways, promoting proliferation, EMT, metastasis, and therapy resistance.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "causal", "source_pmcid": "PMC12142858" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation maintains cell-surface expression for reliable IHC detection.", "mechanism": "High TROP-2 expression independently predicts poor overall and disease-free survival.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation may affect ADC uptake and efficacy.", "mechanism": "TROP-2-directed therapies disrupt EMT and pro-survival signaling, overcoming resistance.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation enables subtype-specific cell-surface presentation.", "mechanism": "Basal-like TNBC subtype shows highest TROP-2 expression, supporting molecular stratification.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation supports CTC surface stability and immune evasion.", "mechanism": "TROP-2 expression on circulating tumor cells (CTCs) is linked to immune escape and distant metastasis.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation enables cell-surface detection.", "mechanism": "TROP-2 overexpression is associated with aggressive disease and poor prognosis.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation supports membrane localization.", "mechanism": "TROP-2 overexpression marks aggressive tumors.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation required for cell-surface expression.", "mechanism": "TROP-2 overexpression correlates with poor prognosis.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142858" }, { "confidence": "medium", "disease": "Hyperinsulinaemia (HI)", "glycan_involvement": "CEACAM-1 is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "CEACAM-1 gene expression is upregulated in livers of HI horses, suggesting altered insulin clearance machinery.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "N-glycosylation affects CEACAM-1 stability and receptor interactions.", "mechanism": "Reduced hepatic CEACAM-1 expression in humans/mice is associated with insulin resistance and increased hepatic lipid accumulation.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates CEACAM-1-mediated endocytosis of insulin-receptor complexes.", "mechanism": "Lower CEACAM-1 expression correlates with increased hepatic lipid accumulation and MASLD in humans/mice.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "Steatosis", "glycan_involvement": "Glycosylation required for CEACAM-1 function in hepatocytes.", "mechanism": "CEACAM-1 deletion in mice leads to steatosis via increased hepatic lipid synthesis.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143019" }, { "confidence": "medium", "disease": "Equine Metabolic Syndrome (EMS)", "glycan_involvement": "Glycosylation status may affect CEACAM-1 activity in EMS.", "mechanism": "Altered CEACAM-1 expression may reflect hepatic insulin clearance dysfunction in EMS.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143019" }, { "confidence": "medium", "disease": "Hyperinsulinaemia (HI)", "glycan_involvement": "IDE is not a glycoprotein; no direct glycan involvement.", "mechanism": "IDE activity is negatively correlated with serum insulin; lower IDE activity may contribute to HI.", "protein": "IDE", "relationship_type": "biomarker", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Not applicable.", "mechanism": "Reduced IDE activity in obese humans aggravates HI and facilitates onset of type 2 diabetes.", "protein": "IDE", "relationship_type": "causal", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Not applicable.", "mechanism": "Hepatic IDE ablation in mice causes HI and glucose intolerance.", "protein": "IDE", "relationship_type": "causal", "source_pmcid": "PMC12143019" }, { "confidence": "low", "disease": "Laminitis", "glycan_involvement": "Glycosylation may affect CEACAM-1 function in insulin clearance, impacting laminitis risk.", "mechanism": "HI and altered CEACAM-1 expression are associated with laminitis risk in horses.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143019" }, { "confidence": "low", "disease": "Steatosis", "glycan_involvement": "Glycosylation may modulate CEACAM-1 protective effects.", "mechanism": "Higher CEACAM-1 expression may compensate for reduced IDE activity and protect against steatosis in HI horses.", "protein": "CEACAM-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12143019" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycosylation of GP is essential for receptor interaction and immune evasion.", "mechanism": "GP mediates viral entry into host immune and endothelial cells via receptor binding.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation modulates GP's cytopathic effects on endothelium.", "mechanism": "GP-induced endothelial cell damage increases vascular permeability and triggers DIC.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Multi-organ failure", "glycan_involvement": "Glycosylation supports GP stability and immune modulation.", "mechanism": "GP-driven viral replication and cytokine storm lead to organ dysfunction.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "DC-SIGN recognizes glycan moieties on GP for binding.", "mechanism": "DC-SIGN acts as a receptor for GP, facilitating viral entry into dendritic cells.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "causal", "source_pmcid": "PMC12143254" }, { "confidence": "medium", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Targets glycosylated epitopes on GP.", "mechanism": "MBP091 binds GP, neutralizing virus and preventing cell entry.", "protein": "MBP091 monoclonal antibody", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143254" }, { "confidence": "medium", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Recognizes glycan-dependent conformational epitopes.", "mechanism": "mAb114 neutralizes GP, blocking infection.", "protein": "mAb114 monoclonal antibody", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity.", "mechanism": "GP antigen detected by ELISA for diagnosis.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycosylation influences immunogenicity and vaccine efficacy.", "mechanism": "GP is the target for vaccine and antibody development.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143254" }, { "confidence": "medium", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "DC-SIGN's glycan-binding domain mediates interaction with viral GP.", "mechanism": "Expression of DC-SIGN on dendritic cells correlates with susceptibility to infection.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143254" }, { "confidence": "medium", "disease": "Marburg virus disease (MVD)", "glycan_involvement": "Glycan-dependent epitopes are critical for antibody binding.", "mechanism": "Antibodies against GP confer protection in experimental models.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "protective", "source_pmcid": "PMC12143254" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "IgY glycosylation affects stability and antigen binding.", "mechanism": "IgY neutralizes rabies virus by binding to rabies glycoprotein, preventing viral entry into host cells.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143637" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation is essential for proper folding and immune evasion.", "mechanism": "Rabies glycoprotein mediates viral attachment and entry into host neurons.", "protein": "Rabies virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12143637" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Glycosylation modulates IgY's interaction with bacterial antigens.", "mechanism": "IgY can be used to neutralize periodontal pathogens.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143637" }, { "confidence": "medium", "disease": "Gastric ulcer", "glycan_involvement": "Glycosylation influences IgY's mucosal stability.", "mechanism": "IgY binds and neutralizes Helicobacter pylori or ulcer-related antigens.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143637" }, { "confidence": "medium", "disease": "Toxin-mediated diseases", "glycan_involvement": "Glycosylation affects IgY's resistance to proteolysis.", "mechanism": "IgY neutralizes toxins by binding to them.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143637" }, { "confidence": "low", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation modulates its immunomodulatory properties.", "mechanism": "Alpha-1-acid glycoprotein is an acute-phase reactant elevated in inflammation.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12143637" }, { "confidence": "low", "disease": "Egg allergy", "glycan_involvement": "Glycosylation may affect allergenicity.", "mechanism": "Vitellogenin-1 is a precursor of egg yolk proteins, implicated in allergic reactions.", "protein": "Vitellogenin-1", "protein_enriched": { "function": "Functions as transport protein in the blood stream", "gene_name": "ogchi", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JIG5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143637" }, { "confidence": "low", "disease": "Egg allergy", "glycan_involvement": "Glycosylation may affect allergenicity.", "mechanism": "Vitellogenin-2 is another egg yolk precursor protein involved in allergy.", "protein": "Vitellogenin-2", "protein_enriched": { "function": "Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled recepto", "gene_name": "FSHB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JIG4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143637" }, { "confidence": "low", "disease": "African Horse Sickness", "glycan_involvement": "Glycosylation may affect IgY's antiviral activity.", "mechanism": "IgY could be developed to neutralize African Horse Sickness virus.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "protective", "source_pmcid": "PMC12143637" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation may influence detection sensitivity.", "mechanism": "IgY titers serve as a biomarker for immune response post-immunization.", "protein": "Immunoglobulin Y (IgY)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA2", "glycan_count": 120, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03382KH", "G03644CB", "G05724UK", "G06110VR", "G06356OH", "G14669DU", "G23294PN", "G23432EQ", "G24835MQ", "G26403SG", "G31916IQ", "G31936TA", "G33609NS", "G39188ZX", "G44211QA", "G46902YN", "G48414YA", "G50045TK", "G56284ZY", "G59626AS", "G60145BJ", "G64527OM", "G66760KM", "G70101JE", "G72291OX", "G72797UR", "G79568CQ", "G81295CK", "G82463GQ", "G83646BJ", "G84452RH", "G02628JF", "G04672QB", "G05850WN", "G06247RL", "G06853GH", "G08146BT", "G08293MJ", "G10256JP", "G11870QZ", "G12580WI", "G14440NQ", "G14994KB", "G20956ZV", "G22310AV", "G23863VK", "G25987BV", "G31986NC", "G36670VW", "G44953PJ", "G45495MK", "G46524LG", "G46687AB", "G47518TP", "G47737VJ", "G49018RC", "G49874UX", "G51640FO", "G52527GH", "G54600FO", "G54845IR", "G56903ZB", "G57818FI", "G59536GA", "G59937CP", "G61613II", "G61627IG", "G64275UO", "G65184UU", "G65219TP", "G66163OV", "G68318VE", "G70822IO", "G72667IM", "G72790NZ", "G72791KH", "G74724QE", "G75983OB", "G76613WN", "G80223IX", "G81263BG", "G83555HU", "G85740DB", "G86226EA", "G86752LQ", "G88374WZ", "G88725PI", "G91473PK", "G91636VS", "G92129PT", "G93683YO", "G94854LT", "G95977AE", "G01650EU", "G09528DL", "G10773YW", "G15038BD", "G45504EY", "G62595EF", "G66621EA", "G82830MN", "G94917XT", "G16276PY", "G20425TQ", "G22140GZ", "G23453IV", "G33780DA", "G36131WL", "G37868ZX", "G39619TI", "G42358LZ", "G43157UW", "G47681UP", "G52706RS", "G55052CN", "G55220VL", "G61937QU", "G75798PH" ], "uniprot_id": "P01877" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143637" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I affects its antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are diagnostic for APS and mediate pathogenic thrombosis.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "arterial thrombosis", "glycan_involvement": "Glycan structures modulate immune recognition and prothrombotic activity.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I promote arterial clot formation in APS.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "venous thrombosis", "glycan_involvement": "Glycosylation influences \u03b22-glycoprotein I's interaction with phospholipids and immune cells.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies increase risk of venous thromboembolism in APS.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12143650" }, { "confidence": "medium", "disease": "microvascular thrombosis", "glycan_involvement": "Glycan modifications may affect microvascular localization and immune complex formation.", "mechanism": "Autoantibody-mediated targeting of \u03b22-glycoprotein I leads to microvascular occlusion.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12143650" }, { "confidence": "medium", "disease": "pregnancy complications (fetal loss, miscarriage)", "glycan_involvement": "Glycosylation may alter placental binding and immune activation.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies disrupt placental function, leading to fetal loss.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "IgG/IgM glycosylation affects antibody effector function and pathogenicity.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of immunoglobulins may influence lupus anticoagulant activity.", "mechanism": "Lupus anticoagulant positivity is a laboratory criterion for APS diagnosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12143650" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Altering glycosylation could affect immunogenicity and therapeutic response.", "mechanism": "\u03b22-glycoprotein I is targeted by autoantibodies; modulation may reduce thrombosis risk.", "protein": "\u03b22-glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycan status may influence antibody binding and risk stratification.", "mechanism": "Triple positivity (lupus anticoagulant, anticardiolipin, anti-\u03b22-glycoprotein I) indicates high-risk APS.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "arterial thrombosis", "glycan_involvement": "Glycosylation may modulate risk by affecting immune complex formation.", "mechanism": "Triple-positive APS patients (including anti-\u03b22-glycoprotein I) have increased arterial thrombosis risk.", "protein": "\u03b22-glycoprotein I", "relationship_type": "risk_marker", "source_pmcid": "PMC12143650" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation mediates host-pathogen interactions and immune evasion.", "mechanism": "Highly polymorphic mucin glycoprotein involved in host cell invasion; sequence variation correlates with virulence and host adaptation.", "protein": "GP60", "protein_enriched": { "function": "May play a role in reproduction", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9U6V9" }, "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation likely facilitates host cell attachment.", "mechanism": "Invasion-associated mucin glycoprotein; sequence polymorphisms linked to increased infectivity and pathogenicity.", "protein": "Mucin 5", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation mediates adhesion to host cells.", "mechanism": "Polymorphic mucin glycoprotein associated with host cell invasion and virulence.", "protein": "Mucin 7", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation implicated in host interaction.", "mechanism": "Polymorphic mucin glycoprotein; sequence variation associated with virulence differences among subtypes.", "protein": "Mucin 11", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation likely important for function.", "mechanism": "Invasion-associated mucin glycoprotein; polymorphisms linked to virulence.", "protein": "Mucin 17", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "Predicted glycosylation may affect secretion and host interaction.", "mechanism": "Secretory glycoproteins with copy number variation; associated with host adaptation and virulence.", "protein": "MEDLE proteins", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "Putative glycosylation; function may involve secretion and intracellular growth.", "mechanism": "Highly polymorphic secretory protein; gene deletion reduces parasite fitness and virulence in mice.", "protein": "cgd8_5420 protein", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "Putative glycosylation may affect protein function.", "mechanism": "Presence correlates with severe clinical signs (diarrhea) in infected mice; deletion reduces severity.", "protein": "cgd8_5420 protein", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "low", "disease": "Cryptosporidiosis", "glycan_involvement": "Predicted glycosylation may modulate host interaction.", "mechanism": "Secretory protein; gene insertion associated with host adaptation and possibly increased virulence.", "protein": "SKSR protein", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "low", "disease": "Cryptosporidiosis", "glycan_involvement": "Putative glycosylation may affect secretion or activity.", "mechanism": "Gene insertion in virulent subtypes; may contribute to host adaptation and virulence.", "protein": "Insulinase-like protease", "relationship_type": "causal", "source_pmcid": "PMC12143685" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates ECM interactions and cell adhesion.", "mechanism": "ECM glycoprotein upregulated in DMD, drives fibrosis and impairs muscle regeneration.", "protein": "Fibronectin 1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation affects cell signaling and immune cell recruitment.", "mechanism": "Upregulated in DMD, promotes ECM deposition and fibrosis.", "protein": "Osteopontin (SPP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation stabilizes TIMP1 and regulates its inhibitory activity.", "mechanism": "Inhibits MMPs, upregulated in DMD, drives fibrosis; DMF suppresses TIMP1.", "protein": "TIMP1", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "high", "disease": "Muscle inflammation", "glycan_involvement": "Glycosylation required for cell surface expression and immune recognition.", "mechanism": "Macrophage glycoprotein marker; increased infiltration in DMD muscle.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation modulates IGF1 stability and receptor binding.", "mechanism": "Upregulated by glucocorticoids; promotes muscle growth but also fibrosis.", "protein": "IGF1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation affects inhibitory function.", "mechanism": "Upregulated in DMD muscle, part of Bmp4-induced fibrotic signature.", "protein": "Serping1", "relationship_type": "biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation required for secretion and protease activity.", "mechanism": "Bmp4-induced upregulation in DMD muscle, contributes to ECM remodeling.", "protein": "Adamts3", "relationship_type": "biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle inflammation", "glycan_involvement": "Glycosylation affects receptor localization and ligand binding.", "mechanism": "HCAR2 agonism by DMF modulates immune response and reduces inflammation.", "protein": "HCAR2", "protein_enriched": { "function": "High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhi", "gene_name": "MTNR1B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P49286" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle adiposis", "glycan_involvement": "Glycosylation influences lipid droplet association.", "mechanism": "Marks adipocyte infiltration in muscle; DMF reduces perilipin-1+ cells.", "protein": "Perilipin-1", "protein_enriched": { "function": "Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular l", "gene_name": "PLIN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60240" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation regulates secretion and proteolytic activity.", "mechanism": "ECM-degrading glycoprotein; imbalance with TIMP1 drives fibrosis in DMD.", "protein": "MMP2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12143770" }, { "confidence": "high", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "Bilirubin is transported in blood bound to albumin (a glycoprotein); glycosylation may affect transport and clearance.", "mechanism": "Elevated serum bilirubin (often glycoprotein-bound) is a diagnostic and severity marker for AH.", "protein": "bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated AST/ALT ratio is used as a diagnostic criterion for AH.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect enzyme activity.", "mechanism": "ALT is measured alongside AST to determine the AST/ALT ratio for AH diagnosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "Glycosylation affects albumin half-life and function.", "mechanism": "Serum albumin (a glycoprotein) is used in liver function assessment; hypoalbuminemia indicates severity.", "protein": "albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion and function.", "mechanism": "Prothrombin time (INR) is used to assess liver synthetic function in AH.", "protein": "prothrombin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Alcohol-related hepatitis (AH)", "glycan_involvement": "N-glycosylation affects fibrinogen stability and clotting function.", "mechanism": "Fibrinogen (a glycoprotein) is involved in coagulation; levels are altered in severe liver disease.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "high", "disease": "Alcohol-related liver disease (ALD)", "glycan_involvement": "Deficient N-glycosylation (carbohydrate-deficient transferrin) is diagnostic.", "mechanism": "Altered glycosylation of transferrin (carbohydrate-deficient transferrin) is a marker of chronic alcohol abuse.", "protein": "transferrin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation may affect albumin function in cirrhosis.", "mechanism": "Low serum albumin is a marker of advanced liver disease (cirrhosis).", "protein": "albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation is required for prothrombin function.", "mechanism": "Prolonged prothrombin time (INR) reflects impaired liver synthesis in cirrhosis.", "protein": "prothrombin", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation is essential for fibrinogen secretion.", "mechanism": "Fibrinogen levels are decreased in advanced cirrhosis, reflecting impaired synthesis.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC12143810" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "MDA5 is a glycoprotein; glycosylation may affect its immune recognition.", "mechanism": "Anti-MDA5 antibodies are diagnostic for a DM subtype, associated with higher disease activity and risk of ILD.", "protein": "MDA5 (Melanoma Differentiation-Associated Gene 5)", "protein_enriched": { "function": "Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including t", "gene_name": "IFIH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYX4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143970" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate MDA5 antigenicity.", "mechanism": "Rare coexistence; anti-MDA5 antibodies may indicate overlap syndrome with SLE.", "protein": "MDA5 (Melanoma Differentiation-Associated Gene 5)", "protein_enriched": { "function": "Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including t", "gene_name": "IFIH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYX4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "C3 is heavily glycosylated; glycan changes may affect complement activation.", "mechanism": "C3 hypocomplementemia is a marker of active SLE.", "protein": "C3 Complement Component", "relationship_type": "biomarker", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG used to treat DM symptoms.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Rituximab glycosylation affects efficacy and immune clearance.", "mechanism": "Rituximab depletes B cells, reducing DM activity.", "protein": "Rituximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation impacts antibody-dependent cytotoxicity.", "mechanism": "Rituximab used for SLE management, especially with hematologic involvement.", "protein": "Rituximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "IFN-I is glycosylated; glycan status may affect receptor binding.", "mechanism": "IFN-I pathway activation drives DM pathogenesis, especially anti-MDA5 subtype.", "protein": "Type I Interferon (IFN-I)", "relationship_type": "causal", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation may influence IFN-I stability and activity.", "mechanism": "IFN-I signaling is central to SLE pathogenesis.", "protein": "Type I Interferon (IFN-I)", "relationship_type": "causal", "source_pmcid": "PMC12143970" }, { "confidence": "medium", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Tacrolimus is derived from a glycosylated natural product.", "mechanism": "Tacrolimus suppresses T-cell activation, improving DM symptoms.", "protein": "Tacrolimus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143970" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects drug metabolism and efficacy.", "mechanism": "Tacrolimus used for SLE, especially with renal or hematologic involvement.", "protein": "Tacrolimus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143970" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "LRG is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "LRG is upregulated in response to cytokines (other than IL-6) during intestinal inflammation and reflects endoscopic and histological activity in UC.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "CRP is N-glycosylated, which may influence its clearance and function.", "mechanism": "CRP is produced in response to IL-6 during systemic inflammation and correlates with UC activity, especially in active disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation may modulate LRG's serum detectability.", "mechanism": "LRG reflects intestinal inflammation more specifically than CRP.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation affects CRP's solubility and function.", "mechanism": "CRP is a general marker of systemic inflammation, not specific to UC.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may affect LRG's immunoreactivity in assays.", "mechanism": "LRG is more effective than CRP for assessing moderate to severe UC activity (MES 2 vs 3).", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation state may influence CRP's half-life.", "mechanism": "CRP is less sensitive than fecal biomarkers for remission but useful for active disease assessment.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may impact LRG's serum stability.", "mechanism": "LRG levels correlate with both endoscopic and histological healing in UC.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Hemoglobin is a glycoprotein; glycosylation may affect detection sensitivity.", "mechanism": "FIT detects bleeding due to mucosal inflammation in UC; high accuracy for mucosal healing.", "protein": "Fecal immunochemical occult blood test (FIT, detects hemoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may affect LRG's function and detection.", "mechanism": "LRG is valuable for distinguishing moderate from severe endoscopic activity (MES 2 vs 3).", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may modulate CRP's biological activity.", "mechanism": "CRP is useful for assessing active inflammation but less so for remission.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144207" }, { "confidence": "high", "disease": "Varicella-Zoster Virus Myelitis", "glycan_involvement": "Glycosylation of VZV envelope proteins is essential for infectivity and immune evasion.", "mechanism": "VZV glycoproteins mediate viral entry and neurotropism, leading to CNS infection and myelitis.", "protein": "Varicella-Zoster Virus Glycoproteins (e.g., gE, gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144282" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates HIV entry into CD4+ T cells, causing immunodeficiency and increased risk of VZV reactivation.", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12144282" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation affects CD4 stability and HIV binding.", "mechanism": "CD4 count reflects immune status; low levels increase susceptibility to VZV myelitis.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "Varicella-Zoster Virus Myelitis", "glycan_involvement": "Fc glycosylation modulates IgG effector functions.", "mechanism": "VZV-specific IgG in CSF indicates intrathecal antibody synthesis and active CNS infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "VZV Vasculopathy", "glycan_involvement": "Glycosylation enables immune evasion and vascular tropism.", "mechanism": "VZV glycoproteins facilitate vascular infection and inflammation.", "protein": "Varicella-Zoster Virus Glycoproteins (e.g., gE, gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144282" }, { "confidence": "high", "disease": "Varicella-Zoster Virus Myelitis", "glycan_involvement": "Indirect; glycoprotein-mediated entry allows access to neuronal cells.", "mechanism": "Targeted by antiviral drugs (acyclovir, ganciclovir) to inhibit viral replication.", "protein": "VZV DNA Polymerase (UL30)", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Altered glycosylation in HIV can affect IgG function.", "mechanism": "Elevated IgG in CSF may reflect chronic immune activation in HIV.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "Varicella-Zoster Virus Myelitis", "glycan_involvement": "Glycosylation modulates CD4 interactions with HIV and immune signaling.", "mechanism": "Adequate CD4+ T cell levels protect against VZV reactivation and CNS disease.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "Longitudinally Extensive Transverse Myelitis", "glycan_involvement": "Glycosylation is critical for neurotropism.", "mechanism": "VZV glycoprotein-mediated neuroinvasion leads to demyelination and extensive spinal cord involvement.", "protein": "Varicella-Zoster Virus Glycoproteins (e.g., gE, gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144282" }, { "confidence": "medium", "disease": "Lumbosacral Plexopathy", "glycan_involvement": "Glycosylation facilitates neuronal infection.", "mechanism": "VZV glycoproteins enable infection of lumbosacral nerve roots.", "protein": "Varicella-Zoster Virus Glycoproteins (e.g., gE, gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144282" }, { "confidence": "high", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "SCC antigen is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "Elevated SCC antigen levels are associated with SCCP diagnosis and progression.", "protein": "SCC antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "CEA is a heavily glycosylated glycoprotein; glycosylation is essential for its function and immunodetection.", "mechanism": "CEA levels are typically normal in SCCP, helping to distinguish from adenocarcinoma.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "CA19-9 is a sialylated glycan epitope on glycoproteins; glycosylation is required for antigenicity.", "mechanism": "CA19-9 levels are typically normal in SCCP, distinguishing it from pancreatic adenocarcinoma.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "High Ki-67 index correlates with rapid tumor proliferation and poor prognosis.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "medium", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "CK20 is a glycoprotein; glycosylation may affect antibody recognition.", "mechanism": "CK20 negativity helps exclude gastrointestinal origin of tumor.", "protein": "CK20", "protein_enriched": { "function": "Plays a significant role in maintaining keratin filament organization in intestinal epithelia. When phosphorylated, plays a role in the secretion of mucin in the small intestine (By similarity)", "gene_name": "KRT20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35900" }, "relationship_type": "diagnostic marker", "source_pmcid": "PMC12144345" }, { "confidence": "medium", "disease": "Primary squamous cell carcinoma of the pancreas (SCCP)", "glycan_involvement": "CK5/6 are glycoproteins; glycosylation may affect detection.", "mechanism": "CK5/6 positivity supports squamous cell origin.", "protein": "CK5/6", "relationship_type": "diagnostic marker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation is essential for CEA antigenicity.", "mechanism": "CEA is often elevated in pancreatic adenocarcinoma.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation is required for CA19-9 epitope formation.", "mechanism": "CA19-9 is frequently elevated in pancreatic adenocarcinoma.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor", "glycan_involvement": "Not a glycoprotein.", "mechanism": "High Ki-67 index predicts poor prognosis and recurrence.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not a glycoprotein.", "mechanism": "High Ki-67 index is associated with poor prognosis.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12144345" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Glycosylation affects folding, antigenicity, and immune recognition.", "mechanism": "E mediates viral entry via receptor binding and membrane fusion.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Glycosylation may modulate epitope exposure and antibody binding.", "mechanism": "DIII is a major target for neutralizing antibodies; vaccines targeting DIII can elicit protective immunity.", "protein": "Envelope glycoprotein domain III (DIII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Antibody-dependent enhancement (ADE)", "glycan_involvement": "Glycosylation can affect antibody binding and ADE risk.", "mechanism": "Non-neutralizing antibodies to E promote Fc\u03b3R-mediated uptake, increasing infection and severity.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "No direct glycan modification, but epitope masking may alter glycan accessibility.", "mechanism": "Engineered to mask non-neutralizing epitopes, rs2DIII-Ala30 elicits broadly neutralizing antibodies against DENV1-3.", "protein": "Resurfaced DENV2 DIII (rs2DIII-Ala30)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "No direct glycan modification, but epitope engineering may affect glycan presentation.", "mechanism": "Engineered to preserve lateral ridge epitope, rs4DIII variants elicit DENV4-specific neutralizing antibodies.", "protein": "Resurfaced DENV4 DIII (rs4DIII-1, -8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Severe dengue (hemorrhagic fever/shock syndrome)", "glycan_involvement": "No direct glycan modification, but nanoparticle display may enhance immune recognition via glycan-mediated pathways.", "mechanism": "Vaccination with rs2DIII-Ala30 nanoparticles reduces viremia and risk of severe disease in mouse models.", "protein": "Resurfaced DENV2 DIII (rs2DIII-Ala30)", "relationship_type": "protective", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Nanoparticle platforms may enhance immunogenicity via glycan-mediated innate immune recognition.", "mechanism": "Two-component nanoparticle cocktail elicits broadly neutralizing antibodies against all four DENV serotypes.", "protein": "Resurfaced DENV2 DIII (rs2DIII-Ala30) + Resurfaced DENV4 DIII (rs4DIII-1, -8)", "relationship_type": "protective", "source_pmcid": "PMC12144416" }, { "confidence": "medium", "disease": "Severe dengue (hemorrhagic fever/shock syndrome)", "glycan_involvement": "NS1 glycosylation affects secretion and immune modulation.", "mechanism": "Elevated NS1 in blood correlates with endothelial dysfunction and severe disease.", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12144416" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "aaLS nanoparticles stimulate mannose-binding lectin-mediated innate immunity.", "mechanism": "aaLS nanoparticles displaying DIII domains enhance immunogenicity and antibody responses.", "protein": "Aquifex aeolicus Lumazine synthase (aaLS)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y8N3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144416" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "hpFer nanoparticles stimulate mannose-binding lectin-mediated innate immunity.", "mechanism": "hpFer nanoparticles displaying DIII domains enhance immunogenicity and antibody responses.", "protein": "Helicobacter pylori Ferritin (hpFer)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O25710" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144416" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "gp60 is a heavily glycosylated surface protein involved in host cell attachment and immune evasion.", "mechanism": "gp60 gene is used for subtyping C. hominis, which causes cryptosporidiosis.", "protein": "60-kDa glycoprotein (gp60)", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "high", "disease": "Giardiasis", "glycan_involvement": "Beta-giardin is a structural protein; glycosylation may affect cyst wall formation and infectivity.", "mechanism": "Beta-giardin gene sequence is used to genotype Giardia lamblia assemblages associated with giardiasis.", "protein": "Beta-giardin", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "Glycosylation of gp60 is critical for its function in host-parasite interactions.", "mechanism": "gp60 mediates host cell attachment and invasion by Cryptosporidium spp.", "protein": "60-kDa glycoprotein (gp60)", "relationship_type": "causal", "source_pmcid": "PMC12144501" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Potential glycosylation may influence protein stability and parasite survival.", "mechanism": "Beta-giardin is essential for Giardia lamblia cytoskeletal integrity and cyst formation, enabling infection.", "protein": "Beta-giardin", "relationship_type": "causal", "source_pmcid": "PMC12144501" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "Glycan epitopes on gp60 are recognized by host antibodies.", "mechanism": "gp60 is a major antigenic target for immune response and vaccine development.", "protein": "60-kDa glycoprotein (gp60)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144501" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Beta-giardin is a candidate for diagnostic and vaccine development.", "protein": "Beta-giardin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144501" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "Subtype-specific glycosylation patterns may affect transmission and immune recognition.", "mechanism": "gp60 subtypes (IbA9G3, IeA11G3T3) indicate anthroponotic transmission routes.", "protein": "60-kDa glycoprotein (gp60)", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Assemblage-specific glycosylation may influence infectivity.", "mechanism": "Sub-assemblages (AII, BIII, BIV) identified by beta-giardin gene are linked to disease epidemiology.", "protein": "Beta-giardin", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "Glycosylation status may affect PCR detection and antigenicity.", "mechanism": "gp60 gene sequencing differentiates C. hominis from other Cryptosporidium spp. in clinical diagnosis.", "protein": "60-kDa glycoprotein (gp60)", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycosylation may impact protein function and disease course.", "mechanism": "Beta-giardin gene is used to distinguish between acute and chronic giardiasis based on assemblage.", "protein": "Beta-giardin", "relationship_type": "biomarker", "source_pmcid": "PMC12144501" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "FUT8-mediated N-glycosylation stabilizes PD-L2 and enhances EGFR/STAT3 signaling.", "mechanism": "Glycosylated PD-L2 binds PD-1, promoting immune evasion and T-cell dysfunction.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "causal", "source_pmcid": "PMC12144609" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Glycosylation stabilizes PD-L1 and is required for its function.", "mechanism": "PD-L1 upregulation suppresses T-cell activity, facilitating tumor immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144609" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Surface glycoprotein; glycosylation required for cell surface localization.", "mechanism": "FAP expression by CAFs promotes immune evasion and tumor progression via PI3K-AKT pathway.", "protein": "FAP (Fibroblast activation protein)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "FAP", "glycan_count": 27, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G37399XV", "G49642SA", "G80920RR", "G11629QQ", "G23010ZW", "G31665QC", "G31852PQ", "G41247ZX", "G43089EG", "G05049YU", "G22310AV", "G27058EU", "G41071NU", "G48414YA", "G59626AS", "G62765YT", "G65184UU", "G84452RH", "G85282JO", "G87661QW", "G15169WU", "G25418HZ", "G37881RL", "G56784JY", "G57888GL", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q12884" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144609" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Binds \u03b2-galactoside glycans on immune cells to mediate effects.", "mechanism": "Promotes immune evasion by inducing apoptosis of T cells and NK cells.", "protein": "Galectin-1", "relationship_type": "causal", "source_pmcid": "PMC12144609" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Binds to glycosylated ligands on immune cells.", "mechanism": "High expression in CAFs limits CD8+ T cell-mediated anti-tumor responses.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "causal", "source_pmcid": "PMC12144609" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Heavily glycosylated; glycosylation affects immune interactions.", "mechanism": "Promotes migration and differentiation of M2 macrophages, enhancing immune suppression.", "protein": "CD276 (B7-H3)", "protein_enriched": { "function": "May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detecti", "gene_name": "CD276", "glycan_count": 79, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G12313PD", "G14796IU", "G18647XP", "G20210JR", "G20312EM", "G22310AV", "G23294PN", "G27058EU", "G27947YN", "G29299MO", "G37399XV", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G44215PV", "G45395BF", "G46902YN", "G47644PP", "G48414YA", "G52527GH", "G55383ZG", "G56784JY", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G63041LO", "G65184UU", "G70619PT", "G72291OX", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G92062TF", "G95865ZB", "G99668VU", "G11629QQ", "G23984SE", "G37881RL", "G43089EG", "G47012YE", "G50427EO", "G57888GL", "G62765YT", "G64394MX", "G64527OM", "G77582RK", "G80075MS", "G85677PP", "G57321FI", "G45504EY", "G83014KM", "G02815KT", "G15169WU", "G25451PN", "G43669FQ", "G75607BQ", "G76417NN", "G80479JV", "G83229XP", "G49108TO" ], "uniprot_id": "Q5ZPR3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144609" }, { "confidence": "medium", "disease": "Chemoresistant HNSCC", "glycan_involvement": "N-glycosylation required for ligand binding and function.", "mechanism": "Upregulated by TAM-secreted IL-1\u03b2, mediates resistance to docetaxel.", "protein": "ICAM1", "relationship_type": "causal", "source_pmcid": "PMC12144609" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Membrane glycoprotein; glycosylation may affect receptor interactions.", "mechanism": "Supports T cell co-stimulation and TLS formation, enhancing anti-tumor immunity.", "protein": "SEMA4A", "protein_enriched": { "function": "Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling (By similarity). Regulates glutamatergic and GABAergic synapse development (By similarit", "gene_name": "SEMA4A", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G10486CT", "G26330YA", "G27058EU", "G00912UN", "G02815KT", "G41247ZX", "G59626AS" ], "uniprot_id": "Q9H3S1" }, "relationship_type": "protective", "source_pmcid": "PMC12144609" }, { "confidence": "high", "disease": "Chemoresistant HNSCC", "glycan_involvement": "N-glycosylation required for receptor function and ligand binding.", "mechanism": "Overexpression upregulates M2 macrophage markers, promoting resistance to cetuximab.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12144609" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding.", "mechanism": "Upregulated by OLR1, associated with stemness and immune evasion.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144609" }, { "confidence": "high", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "EGFR is a glycoprotein; glycosylation is essential for its membrane localization and ligand binding.", "mechanism": "EGFR is upregulated and activated in sorafenib-resistant HCC, promoting EMT and tumor progression via JNK/ERK signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates EGFR function and signaling.", "mechanism": "EGFR activation drives proliferation and survival signaling in HCC.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "N-cadherin is a glycoprotein; glycosylation affects cell adhesion.", "mechanism": "N-cadherin is upregulated during EMT in resistant HCC, marking increased invasiveness.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "medium", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Vimentin is upregulated during EMT, indicating mesenchymal phenotype and resistance.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "medium", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "\u03b2-Tubulin III is elevated in resistant cells, associated with microtubule changes and drug resistance.", "protein": "\u03b2-Tubulin III", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:34996871, PubMed:38305685, PubMed:38609661). Microtubules grow by the add", "gene_name": "TUBB3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G08290VR" ], "uniprot_id": "Q13509" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "medium", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "Some keratins are glycoproteins; glycosylation may affect filament stability.", "mechanism": "Keratin is downregulated during EMT in resistant HCC.", "protein": "Keratin", "protein_enriched": { "function": "May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity recept", "gene_name": "KRT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G22310AV", "G48414YA", "G75983OB" ], "uniprot_id": "P04264" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "EGFR glycosylation is required for proper signaling.", "mechanism": "EGFR/JNK/ERK pathway activation promotes EMT and resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "Targeting glycosylated EGFR may affect drug efficacy.", "mechanism": "Apatinib inhibits EGFR signaling, reversing resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144613" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates adhesion and signaling.", "mechanism": "N-cadherin upregulation marks EMT and poor prognosis.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Sorafenib-resistant hepatocellular carcinoma", "glycan_involvement": "Glycosylation status may influence detection and function.", "mechanism": "High EGFR expression correlates with resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144613" }, { "confidence": "high", "disease": "Pyogenic liver abscess", "glycan_involvement": "Capsule is a polysaccharide (glycan) structure; glycosylation critical for function.", "mechanism": "Capsule enhances virulence by resisting phagocytosis and neutrophil killing, promoting abscess formation.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "high", "disease": "Klebsiella pneumoniae invasive syndrome", "glycan_involvement": "Capsular glycan structure is essential for immune evasion.", "mechanism": "Capsule enables dissemination and immune evasion, leading to invasive disease.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "high", "disease": "Gram-negative bacteremia", "glycan_involvement": "Glycosylation of capsule is required for serum resistance.", "mechanism": "Capsule prevents complement-mediated killing, facilitating bloodstream infection.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "medium", "disease": "Antibiotic resistance", "glycan_involvement": "Enzyme may be glycosylated for stability or secretion, though not specified.", "mechanism": "SHV ESBL hydrolyzes beta-lactam antibiotics, conferring resistance.", "protein": "SHV extended-spectrum beta-lactamase (SHV ESBL)", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "medium", "disease": "Urinary tract infection", "glycan_involvement": "Fimbrial glycoproteins interact with host glycans.", "mechanism": "Fimbriae mediate adhesion to uroepithelial cells, initiating infection.", "protein": "Fimbriae (pili)", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "medium", "disease": "Endophthalmitis", "glycan_involvement": "Capsular glycan structure mediates immune evasion.", "mechanism": "Capsule allows hematogenous spread to the eye.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation of capsule is essential for virulence.", "mechanism": "Capsule protects against lung immune defenses.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "medium", "disease": "Pyogenic liver abscess", "glycan_involvement": "Possible glycosylation for enzyme function, not specified.", "mechanism": "SHV ESBL-producing strains are more difficult to treat, leading to persistent abscess.", "protein": "SHV extended-spectrum beta-lactamase (SHV ESBL)", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "Dense glycan layer acts as a barrier.", "mechanism": "Capsule may impede antibiotic penetration.", "protein": "Klebsiella pneumoniae capsular polysaccharide", "relationship_type": "protective", "source_pmcid": "PMC12144673" }, { "confidence": "low", "disease": "Klebsiella pneumoniae invasive syndrome", "glycan_involvement": "Fimbrial glycoproteins bind host glycans.", "mechanism": "Fimbriae facilitate tissue colonization and invasion.", "protein": "Fimbriae (pili)", "relationship_type": "causal", "source_pmcid": "PMC12144673" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antibody binding and pathogenicity.", "mechanism": "AQP4-IgG autoantibodies target AQP4 glycoprotein on astrocytes, causing demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation of AQP4 may modulate immune recognition.", "mechanism": "AQP4-IgG positivity in SLE patients indicates overlap with NMOSD and predicts CNS involvement.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "MOG is a glycoprotein; glycosylation influences antigenicity.", "mechanism": "MOG-IgG autoantibodies are found in AQP4-IgG-negative NMOSD, indicating a distinct pathogenesis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Sema3A is a glycoprotein; glycosylation may affect its immunoregulatory function.", "mechanism": "Serum Sema3A levels inversely correlate with SLE disease activity; involved in immune regulation.", "protein": "Semaphorin 3A (Sema3A)", "protein_enriched": { "function": "Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth", "gene_name": "SEMA3A", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G70994MS", "G80920RR" ], "uniprot_id": "Q14563" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Neuropilin-1 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "Neuropilin-1, as Sema3A receptor, is implicated in SLE pathogenesis and immune modulation.", "protein": "Neuropilin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Target glycoproteins may have altered glycosylation in SLE.", "mechanism": "ANA are diagnostic for SLE; target nuclear glycoproteins.", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "SSA/Ro is a glycoprotein; glycosylation may affect autoantibody recognition.", "mechanism": "Anti-SSA/Ro antibodies are common in SLE and overlap syndromes.", "protein": "Anti-Sj\u00f6gren\u2019s syndrome-related antigen A (anti-SSA/Ro)", "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "LDG surface glycoproteins may be altered in SLE.", "mechanism": "Elevated LDGs are associated with SLE disease activity and inflammation.", "protein": "Low-density granulocyte (LDG) surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "Receptor is a glycoprotein; glycosylation may influence autoantibody binding.", "mechanism": "Acetylcholine receptor antibodies are found in NMOSD but not in MS or healthy controls.", "protein": "Acetylcholine receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Targets glycosylated AQP4.", "mechanism": "NMO-IgG binds AQP4 glycoprotein, predicts NMOSD relapse.", "protein": "Neuromyelitis optica immunoglobulin (NMO-IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12144925" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Autoantibodies against MOG cause CNS demyelination, leading to MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12145056" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation of MOG may influence immune recognition and pathogenicity.", "mechanism": "Anti-MOG antibodies trigger inflammation and demyelination of the optic nerve.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation status may affect diagnostic specificity.", "mechanism": "MOG antibodies are tested to differentiate MOGAD from MS.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "AQP4 antibodies are diagnostic for NMOSD, distinguishing it from MOGAD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may affect antigenic differences between MOG and AQP4.", "mechanism": "MOG antibody testing helps distinguish MOGAD from NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Relapsing demyelinating disease", "glycan_involvement": "Glycosylation may modulate immune response and antibody persistence.", "mechanism": "Persistently elevated MOG antibody titers predict relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Spinal cord lesions (in MOGAD)", "glycan_involvement": "Glycosylation may influence tissue-specific immune targeting.", "mechanism": "Anti-MOG antibodies cause demyelinating lesions in the spinal cord.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Brain lesions (in MOGAD)", "glycan_involvement": "Glycosylation may affect MOG's immunogenicity in CNS regions.", "mechanism": "Anti-MOG antibodies cause demyelinating lesions in the brain.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12145056" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "CSF myelin basic protein is used as a marker for demyelination in MS.", "protein": "Myelin basic protein", "relationship_type": "biomarker", "source_pmcid": "PMC12145056" }, { "confidence": "medium", "disease": "Blood\u2013brain barrier dysfunction (in MOGAD)", "glycan_involvement": "Glycosylation of MOG may influence BBB immune interactions.", "mechanism": "Elevated CSF albumin/serum albumin ratio indicates BBB dysfunction in MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145056" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSH indicates thyroid hormone deficiency.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "T4 is transported by glycoprotein carriers; glycosylation affects bioavailability.", "mechanism": "Low free T4 confirms thyroid hormone deficiency.", "protein": "Free thyroxine (T4)", "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "medium", "disease": "Statin-associated myopathy", "glycan_involvement": "Altered TSH glycosylation may affect receptor signaling and downstream muscle metabolism.", "mechanism": "Uncontrolled hypothyroidism (high TSH) increases risk of statin-induced muscle injury.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "CK elevation reflects muscle breakdown.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Myoglobin released from muscle damages renal tubules, causing AKI.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "causal", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Transaminitis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "AST elevation in rhabdomyolysis is muscle-derived, not hepatic.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Transaminitis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "ALT elevation in rhabdomyolysis is muscle-derived, not hepatic.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "Alkaline phosphatase is a glycoprotein; glycosylation affects its activity and clearance.", "mechanism": "Elevated in liver and muscle injury.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "low", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "TSH glycosylation may modulate its renal effects.", "mechanism": "Severe hypothyroidism may reduce renal perfusion, compounding AKI risk.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12145068" }, { "confidence": "medium", "disease": "Statin-associated myopathy", "glycan_involvement": "Autoantibody glycosylation affects immune recognition.", "mechanism": "Negative result excludes autoimmune myositis as a cause.", "protein": "Anti-histidyl-tRNA synthetase antibody (anti-Jo-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12145068" }, { "confidence": "high", "disease": "Breast cancer brain metastasis (BCBM)", "glycan_involvement": "N-glycosylation modulates HER2 stability and antibody binding.", "mechanism": "HER2 overexpression drives tumor growth and metastasis; targeted by antibodies and ADCs.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "Fc glycosylation affects ADCC potency.", "mechanism": "Binds extracellular domain of HER2, blocking signaling and inducing ADCC.", "protein": "Trastuzumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "high", "disease": "Breast cancer brain metastasis (BCBM)", "glycan_involvement": "Glycosylation of trastuzumab component affects pharmacokinetics and efficacy.", "mechanism": "Delivers cytotoxic DM1 to HER2+ cells via trastuzumab targeting.", "protein": "T-DM1 (Trastuzumab emtansine)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "high", "disease": "Breast cancer brain metastasis (BCBM)", "glycan_involvement": "Glycosylation of antibody component influences tissue distribution.", "mechanism": "Delivers potent cytotoxic payload to HER2+ cells, with strong bystander effect.", "protein": "T-DXd (Trastuzumab deruxtecan)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Blocks HER2 dimerization, enhancing trastuzumab efficacy.", "protein": "Pertuzumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "medium", "disease": "Breast cancer brain metastasis (BCBM)", "glycan_involvement": "N-glycosylation regulates EGFR ligand binding and activation.", "mechanism": "Targeted by lapatinib and pyrotinib; EGFR signaling promotes metastasis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "medium", "disease": "Breast cancer brain metastasis (BCBM)", "glycan_involvement": "Cell surface glycoproteins mediate immune recognition.", "mechanism": "Cell-based immunotherapy induces anti-tumor immune response.", "protein": "Bria-IMT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "medium", "disease": "Leptomeningeal disease (LMD)", "glycan_involvement": "Glycosylation affects CNS penetration and immune activation.", "mechanism": "Intrathecal administration targets HER2+ cells in CNS.", "protein": "Trastuzumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "medium", "disease": "Leptomeningeal disease (LMD)", "glycan_involvement": "Antibody glycosylation impacts CNS distribution.", "mechanism": "ADC delivers cytotoxic payload to HER2+ cells in CNS.", "protein": "T-DXd (Trastuzumab deruxtecan)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145366" }, { "confidence": "medium", "disease": "HR+/HER2- breast cancer", "glycan_involvement": "Glycosylation status may affect diagnostic antibody binding.", "mechanism": "HER2 status guides use of trastuzumab; not effective in HER2- subtype.", "protein": "Trastuzumab", "relationship_type": "biomarker", "source_pmcid": "PMC12145366" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG are associated with demyelinating optic neuritis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145498" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Aquaporin-4 is glycosylated; glycosylation may influence antibody binding.", "mechanism": "Autoantibodies against Aquaporin-4 are linked to neuromyelitis optica spectrum disorders presenting with optic neuritis.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145498" }, { "confidence": "high", "disease": "Adult-onset Still's disease (AOSD)", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect its serum stability and clearance.", "mechanism": "Serum ferritin is markedly elevated in AOSD, reflecting systemic inflammation and macrophage activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "high", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation may modulate ferritin's immunogenicity and clearance.", "mechanism": "Extremely high ferritin levels are a hallmark of MAS, a severe complication of AOSD.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "high", "disease": "Adult-onset Still's disease (AOSD)", "glycan_involvement": "CRP is N-glycosylated, which affects its solubility and function.", "mechanism": "CRP is elevated in AOSD, reflecting acute phase response.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "medium", "disease": "Adult-onset Still's disease (AOSD)", "glycan_involvement": "SAA glycosylation influences its aggregation and amyloidogenic potential.", "mechanism": "SAA is an acute phase glycoprotein elevated in systemic inflammation, including AOSD.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "medium", "disease": "Adult-onset Still's disease (AOSD)", "glycan_involvement": "IL-1Ra is glycosylated, which affects its stability and receptor binding.", "mechanism": "IL-1Ra blocks IL-1 signaling, reducing inflammation in AOSD.", "protein": "Interleukin-1 receptor antagonist (IL-1Ra)", "protein_enriched": { "function": "Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. Protects from immune dysregulation and uncontrolled system", "gene_name": "IL1RN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22310AV", "G48414YA" ], "uniprot_id": "P18510" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145864" }, { "confidence": "high", "disease": "Adult-onset Still's disease (AOSD)", "glycan_involvement": "Therapeutic antibody glycosylation affects pharmacokinetics and effector function.", "mechanism": "Canakinumab neutralizes IL-1\u03b2, leading to symptom improvement in AOSD.", "protein": "Canakinumab (anti-IL-1\u03b2 antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145864" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may affect ferritin's immunoreactivity.", "mechanism": "Ferritin is extremely elevated in HLH, indicating hyperinflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "N-glycosylation modulates CRP's function.", "mechanism": "CRP is elevated in MAS, reflecting systemic inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation affects SAA's aggregation.", "mechanism": "SAA is increased in MAS, indicating acute phase response.", "protein": "SAA", "relationship_type": "biomarker", "source_pmcid": "PMC12145864" }, { "confidence": "low", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation affects IL-1Ra's activity.", "mechanism": "IL-1Ra may be used to block IL-1 signaling in MAS.", "protein": "IL-1Ra", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145864" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Elevated SNA, SBA, PSA lectin binding (sialylation, galactosylation, fucosylation).", "mechanism": "Increased sialic acid, galactose, and fucose glycosylation in serum proteins correlates with disease severity.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Elevated AAL, RCA120, SBA, PHA-L lectin binding.", "mechanism": "Increased fucosylation, galactosylation, and biantennary N-glycan structures in blister fluid proteins are associated with disease activity.", "protein": "Blister fluid glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Elevated SNA and AAL lectin binding; SNA increases with improvement, AAL decreases.", "mechanism": "Increased sialic acid and fucose glycosylation in saliva correlates with disease severity and responds to treatment.", "protein": "Salivary glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Altered Fc N-glycosylation affects effector function.", "mechanism": "IgG glycosylation state modulates inflammatory response; galactosylated/sialylated IgG is anti-inflammatory, agalactosylated is pro-inflammatory.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "SNA binding negatively correlates with BP180 antibody titers.", "mechanism": "Autoantibodies against BP180 detected in serum and saliva; salivary glycosylation patterns (especially sialylation) correlate with BP180 antibody titers.", "protein": "BP180", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "PSA and PHA-L binding positively correlate with BP230 titers.", "mechanism": "BP230 antibody titers in serum and saliva correlate with specific glycosylation patterns (e.g., PSA, PHA-L binding).", "protein": "BP230", "protein_enriched": { "function": "Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleto", "gene_name": "DST", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q03001" }, "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Low SNA, high PSA binding.", "mechanism": "Decreased sialic acid and increased fucose in saliva are associated with more severe disease in BP patients negative for salivary BP180 antibodies.", "protein": "Salivary glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Elevated PHA-L binding.", "mechanism": "Increased biantennary N-glycans (PHA-L binding) in blister fluid are associated with disease severity, especially in patients without mucosal involvement.", "protein": "Blister fluid glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "SNA increases, AAL decreases with clinical improvement.", "mechanism": "Dynamic changes in SNA and AAL binding in saliva track disease activity and response to therapy.", "protein": "Salivary glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "SNA negatively with BP180, AAL negatively with eosinophils, PSA positively with ESR.", "mechanism": "SNA, AAL, and PSA binding in serum correlate with clinical indicators (e.g., BP180 titers, eosinophil count, ESR).", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12146333" }, { "confidence": "high", "disease": "Equine Coital Exanthema (ECE)", "glycan_involvement": "Glycosylation of viral envelope proteins is essential for viral infectivity and immune evasion.", "mechanism": "Glycoprotein G gene is targeted by real-time PCR for molecular diagnosis of EHV-3 infection in horses.", "protein": "Glycoprotein G (EHV-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12146816" }, { "confidence": "high", "disease": "Equine Coital Exanthema (ECE)", "glycan_involvement": "Glycosylation facilitates viral entry and cell-to-cell spread.", "mechanism": "Glycoprotein G is a structural component of EHV-3, which causes ECE by infecting genital epithelial cells.", "protein": "Glycoprotein G (EHV-3)", "relationship_type": "causal", "source_pmcid": "PMC12146816" }, { "confidence": "high", "disease": "Vogt-Koyanagi-Harada disease (VKH)", "glycan_involvement": "gp100 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Autoimmune targeting of melanocyte glycoprotein gp100 implicated in VKH pathogenesis.", "protein": "gp100 (melanocyte antigen)", "protein_enriched": { "function": "Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation. The maturation of unpigmented premelanosomes from stage I to II is marked by assembly of processed a", "gene_name": "PMEL", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P40967" }, "relationship_type": "causal", "source_pmcid": "PMC12147045" }, { "confidence": "medium", "disease": "Vogt-Koyanagi-Harada disease (VKH)", "glycan_involvement": "Viral glycoprotein; glycosylation may enhance immune recognition.", "mechanism": "CMV glycoprotein H shares sequence homology with melanin antigens, possibly triggering autoimmunity.", "protein": "CMV envelope glycoprotein H", "protein_enriched": { "function": "This endonuclease is specific to the thymidylate synthase (td) gene splice junction and is involved in intron homing", "gene_name": "ITEVIR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13299" }, "relationship_type": "causal (molecular mimicry, literature-based)", "source_pmcid": "PMC12147045" }, { "confidence": "medium", "disease": "Vogt-Koyanagi-Harada disease (VKH)", "glycan_involvement": "Glycosyltransferase activity may influence glycan structures and antigenicity.", "mechanism": "Earp protein shares high sequence homology with gp100, suggesting potential cross-reactive immune response.", "protein": "Earp protein (Pseudomonas aeruginosa glycosyltransferase A chain)", "relationship_type": "causal (molecular mimicry)", "source_pmcid": "PMC12147045" }, { "confidence": "low", "disease": "Vogt-Koyanagi-Harada disease (VKH)", "glycan_involvement": "Capsid glycoprotein may interact with host immune system.", "mechanism": "Enriched in VKH; Vp1 inhibits Chlamydia and pro-inflammatory cytokines, possible immune modulation.", "protein": "Chlamydiamicrovirus_CPG1 capsid protein Vp1", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12147045" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Glycosylation may affect antigen processing and presentation.", "mechanism": "gp100 is a melanocyte antigen targeted in autoimmune depigmentation.", "protein": "gp100 (melanocyte antigen)", "protein_enriched": { "function": "Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation. The maturation of unpigmented premelanosomes from stage I to II is marked by assembly of processed a", "gene_name": "PMEL", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P40967" }, "relationship_type": "causal", "source_pmcid": "PMC12147045" }, { "confidence": "medium", "disease": "Depigmentation/Leukotrichia", "glycan_involvement": "Glycosyltransferase function may alter glycan antigens.", "mechanism": "Cross-reactivity with melanocyte antigens may trigger depigmentation.", "protein": "Earp protein (Pseudomonas aeruginosa glycosyltransferase A chain)", "relationship_type": "causal (molecular mimicry)", "source_pmcid": "PMC12147045" }, { "confidence": "low", "disease": "Vitiligo", "glycan_involvement": "Glycosylation may enhance immunogenicity.", "mechanism": "Sequence homology with melanocyte antigens may trigger autoimmunity.", "protein": "CMV envelope glycoprotein H", "protein_enriched": { "function": "This endonuclease is specific to the thymidylate synthase (td) gene splice junction and is involved in intron homing", "gene_name": "ITEVIR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13299" }, "relationship_type": "causal (molecular mimicry, literature-based)", "source_pmcid": "PMC12147045" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoproteins; loss impairs glycosylation-dependent membrane stability.", "mechanism": "Loss of dystrophin disrupts the assembly of the sarcolemmal dystrophin-associated glycoprotein complex, causing membrane fragility and muscle damage.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DGC contains heavily glycosylated proteins (e.g., dystroglycan); glycosylation is essential for ECM binding.", "mechanism": "Destabilization of the DGC due to dystrophin deficiency leads to muscle fiber damage and progressive loss of function.", "protein": "Dystrophin-associated glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Myonecrosis", "glycan_involvement": "MYOM3 is a glycoprotein released upon muscle cell membrane disruption.", "mechanism": "Elevated plasma MYOM3 indicates ongoing skeletal muscle fiber necrosis.", "protein": "MYOM3 (Myomesin-3)", "protein_enriched": { "function": "Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'", "gene_name": "Nfrkb", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6PIJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "Troponin T is glycosylated; release is a marker of cardiac muscle damage.", "mechanism": "Elevated plasma hs-cTnT reflects cardiomyocyte necrosis in dystrophin-deficient rats.", "protein": "hs-cTnT (high-sensitivity cardiac troponin T)", "protein_enriched": { "function": "Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P45379" }, "relationship_type": "biomarker", "source_pmcid": "PMC12147255" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin glycosylation is critical for ECM interactions; disruption affects muscle integrity.", "mechanism": "Loss of dystrophin disrupts laminin binding to the muscle cell membrane, impairing ECM-cytoskeleton linkage.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Fibrosis (muscle and cardiac)", "glycan_involvement": "Loss of glycoprotein complex function promotes ECM remodeling and fibrosis.", "mechanism": "Dystrophin deficiency leads to chronic muscle damage, inflammation, and replacement of muscle by fibrotic tissue.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Respiratory failure in DMD", "glycan_involvement": "Disrupted glycoprotein complex affects diaphragm ECM stability.", "mechanism": "Diaphragm muscle dystrophy and fibrosis impair ventilatory function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "Glycosylation of DGC components is essential for cardiac muscle function.", "mechanism": "DGC destabilization leads to cardiac muscle damage and electrical defects (notched T wave, prolonged QTpc).", "protein": "Dystrophin-associated glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Myonecrosis", "glycan_involvement": "Glycoprotein complex disruption increases membrane permeability.", "mechanism": "Absence of dystrophin causes sarcolemma fragility and muscle cell death.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "Loss of glycoprotein-mediated ECM-cytoskeleton linkage impairs cardiac tissue structure.", "mechanism": "Dystrophin deficiency leads to cardiac remodeling, fibrosis, and electrical conduction defects.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12147255" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Decreased glycosylation (especially sulfation) impairs barrier function.", "mechanism": "Reduced mucin-2 and its glycosylation leads to thinning/denudation of mucus, allowing microbial invasion and inflammation.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Altered glycosylation and expression.", "mechanism": "Polymorphisms and decreased mucin-2 associated with altered mucus barrier and increased inflammation.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "Impaired O-glycosylation reduces protective function.", "mechanism": "Stress or infection reduces mucin-2 synthesis/secretion, disrupting barrier and leading to diarrhea.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "high", "disease": "Spontaneous colitis", "glycan_involvement": "Essential for mucin structure and barrier integrity.", "mechanism": "Loss of core 1 O-glycans damages colonic mucus barrier, increasing pathogen access and colitis.", "protein": "Core 1 O-glycans", "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Maintains mucosal integrity.", "mechanism": "Deficiency increases intestinal permeability and susceptibility to colitis.", "protein": "Core 3 O-glycans", "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "O-glycan extension reduces pathogen binding.", "mechanism": "Inhibit pathogenic E. coli invasion by reducing adhesion to epithelium.", "protein": "Core 2 O-glycans", "relationship_type": "protective", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Fucose residues modulate immune response and microbiota.", "mechanism": "Fucosylation supports beneficial microbiota and immune modulation; FUT2 mutations increase colitis risk.", "protein": "Fucosylated mucin", "relationship_type": "protective", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Sialic acid addition critical for network structure.", "mechanism": "Sialylation maintains mucus integrity and provides bacterial attachment sites; loss increases susceptibility.", "protein": "Sialylated mucin", "relationship_type": "protective", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Aberrant glycosylation patterns.", "mechanism": "Decreased mucin-2 and simplified glycosylation associated with tumorigenesis.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12148640" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "Altered O-glycosylation affects mucus properties.", "mechanism": "Abnormal mucin-2 secretion and glycosylation lead to decreased mucus and GI symptoms.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12148640" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation is required for its synaptic vesicle localization and function.", "mechanism": "CSF and PET measures of SV2A are significantly lower in AD, reflecting synaptic loss; CSF SV2A correlates with synaptic density.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Synaptotagmin-1 is a glycoprotein; glycosylation may affect trafficking/function.", "mechanism": "CSF synaptotagmin-1 is elevated in AD; negatively associated with SV2A PET (synaptic density).", "protein": "Synaptotagmin-1", "protein_enriched": { "function": "Calcium sensor that participates in triggering neurotransmitter release at the synapse (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles ", "gene_name": "SYT1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G83014KM" ], "uniprot_id": "P21579" }, "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a classical glycoprotein; palmitoylation is main modification.", "mechanism": "CSF SNAP25 (Total and Long) is elevated in AD; negatively associated with SV2A PET.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF neurogranin is elevated in AD; weak or regionally variable association with SV2A PET.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF GAP-43 is elevated in AD; negatively associated with SV2A PET in some regions.", "protein": "GAP-43", "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF NFL is elevated in AD; negatively associated with SV2A PET in some regions.", "protein": "NFL", "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF syntaxin-1B is elevated in AD; negatively associated with SV2A PET.", "protein": "Syntaxin-1B", "protein_enriched": { "function": "Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a co", "gene_name": "TNFRSF14", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q92956" }, "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF syntaxin-7 is elevated (trend-level) in AD; negatively associated with SV2A PET.", "protein": "Syntaxin-7", "protein_enriched": { "function": "May be involved in protein trafficking from the plasma membrane to the early endosome (EE) as well as in homotypic fusion of endocytic organelles. Mediates the endocytic trafficking from early endosom", "gene_name": "STX7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15400" }, "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CSF PEBP-1 is elevated in AD; robust association with SV2A PET.", "protein": "PEBP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12149441" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of SV2A is required for its function and synaptic localization.", "mechanism": "SV2A reflects synaptic density; potential target for monitoring therapeutic efficacy in AD.", "protein": "SV2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12149441" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for secretion and stability; glycan moieties may influence immune recognition.", "mechanism": "Elevated CHI3L1 reflects neuroinflammation and tissue remodeling in AD; correlates with cognitive decline.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "Glycosylation affects protein folding and secretion.", "mechanism": "CHI3L1 levels can help differentiate AD from FTD; reflects neuroinflammatory processes.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation required for function as a secreted glycoprotein.", "mechanism": "Elevated CHI3L1 indicates neuroinflammation in vascular dementia.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation influences stability and immune interactions.", "mechanism": "Serum CHI3L1 correlates with neurofilament light chain and cognitive impairment in PD.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Lewy body disease", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated CHI3L1 reflects neuroinflammation in Lewy body disease.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Multiple system atrophy", "glycan_involvement": "Glycosylation required for extracellular function.", "mechanism": "CHI3L1 elevation indicates neuroinflammatory activity.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "medium", "disease": "Progressive supranuclear palsy", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "CHI3L1 reflects neuroinflammation in PSP.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "low", "disease": "Creutzfeldt\u2013Jakob disease", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Elevated CHI3L1 may indicate neuroinflammation in CJD.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "high", "disease": "Cognitive impairment (general)", "glycan_involvement": "Glycosylation required for stability and secretion.", "mechanism": "Serum CHI3L1 levels correlate with severity of cognitive deficits (MMSE scores).", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "high", "disease": "Dementia (general)", "glycan_involvement": "Glycosylation required for extracellular activity.", "mechanism": "CHI3L1 serves as a supportive biomarker for neurodegenerative dementia.", "protein": "Chitinase-3-like protein 1 (CHI3L1)", "protein_enriched": { "function": "Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their envi", "gene_name": "CHI3L1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22573RC", "G22768VO" ], "uniprot_id": "P36222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12152271" }, { "confidence": "high", "disease": "Breast Cancer (BC)", "glycan_involvement": "Increased sulfation (mono-sulfated, sialylated, fucosylated N-glycans) on IgG", "mechanism": "Upregulation of mono-sulfated N-glycans on IgG in serum is associated with early-stage BC and can distinguish patients from healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "high", "disease": "Breast Cancer (BC)", "glycan_involvement": "Upregulation of terminal Lewis-type, LacNAc, and sialylated/fucosylated sulfated N-glycans", "mechanism": "Seven mono-sulfated N-glycans in serum are significantly elevated in early-stage BC and serve as predictive biomarkers.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Mono-sulfated N-glycans on IgG", "mechanism": "Trace levels of sulfated N-glycans from IgG are potential biomarkers for rheumatoid arthritis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Pancreatic Cancer", "glycan_involvement": "Upregulation of sulfated N-glycans", "mechanism": "Increase in sulfated N-glycans in serum is noted in pancreatic cancer, suggesting a common glycomic alteration in cancer.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Breast Cancer (BC)", "glycan_involvement": "Sulfation of N-glycans", "mechanism": "Targeting sulfotransferase enzymes responsible for synthesizing specific sulfated N-glycans may impede BC progression and metastasis.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Breast Cancer (BC)", "glycan_involvement": "Sulfated Lewis-type and sialylated N-glycans", "mechanism": "Enhanced sulfation of terminal epitopes (e.g., 6-sulfosialyl LewisX) promotes BC cell migration, invasion, and metastasis.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12154234" }, { "confidence": "high", "disease": "Breast Cancer (BC)", "glycan_involvement": "Fucosylated and sialylated sulfated N-glycans", "mechanism": "Increased fucosylation and sialylation of sulfated N-glycans are statistically significant markers of early-stage BC.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "high", "disease": "Breast Cancer (BC)", "glycan_involvement": "Altered glycan subclass abundance", "mechanism": "Glycan subclass patterns (fucosylated, sialylated, sulfated) in serum are strong predictive indicators for early-stage BC.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Breast Cancer (BC)", "glycan_involvement": "Terminal Lewis-type sulfated N-glycans", "mechanism": "Upregulation of terminal Lewis-type epitopes on sulfated N-glycans facilitates immune cell interactions and may contribute to tumor aggressiveness.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12154234" }, { "confidence": "medium", "disease": "Breast Cancer (BC)", "glycan_involvement": "Sulfated N-glycans on IgG", "mechanism": "Altered sulfation of IgG N-glycans may impact immune recognition and function, influencing BC progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12154234" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for receptor function and cell surface expression.", "mechanism": "IL-18R1 mediates pro-inflammatory signaling, associated with increased plaque burden.", "protein": "IL-18R1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12155917" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "CSF-1 regulates monocyte/macrophage differentiation, promoting plaque development and burden.", "protein": "CSF-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12155917" }, { "confidence": "high", "disease": "Vulnerable plaque", "glycan_involvement": "N-glycosylation modulates secretion and activity.", "mechanism": "ANGPTL3 inhibits LPL, promoting lipid accumulation and lipid-rich plaque formation.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12155917" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "PCSK9 increases LDL cholesterol, associated with both plaque burden and lipid core.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation affects receptor binding and stability.", "mechanism": "VEGFA promotes angiogenesis, elevated after MI and in vulnerable plaques.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Vulnerable plaque", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect secretion.", "mechanism": "EN-RAGE is pro-inflammatory, associated with plaque instability.", "protein": "EN-RAGE (S100A12)", "relationship_type": "biomarker", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Vulnerable plaque", "glycan_involvement": "N-glycosylation required for lysosomal targeting and activity.", "mechanism": "Cathepsin D involved in matrix degradation, linked to plaque vulnerability.", "protein": "Cathepsin D", "relationship_type": "biomarker", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation essential for receptor stability and iron uptake.", "mechanism": "Elevated TR associated with increased MI risk and plaque burden.", "protein": "Transferrin receptor protein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Vulnerable plaque", "glycan_involvement": "O-glycosylation and phosphorylation modulate function.", "mechanism": "Osteopontin is upregulated in atheroma and after MI, linked to inflammation and plaque instability.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12155917" }, { "confidence": "medium", "disease": "Vulnerable plaque", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "LPL hydrolyzes triglycerides; lower levels associated with higher lipid core burden.", "protein": "Lipoprotein lipase", "relationship_type": "protective", "source_pmcid": "PMC12155917" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Binds \u03b2-galactoside glycans on cell surface and ECM; glycan binding is essential for function.", "mechanism": "Promotes inflammation, macrophage activation, and fibrosis; increased in cardiac hypertrophy and HF.", "protein": "Galectin-3 (LGALS3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentia", "gene_name": "LGALS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17931" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12160080" }, { "confidence": "high", "disease": "Pathological cardiac hypertrophy", "glycan_involvement": "Lectin-glycan interactions drive cell signaling and ECM remodeling.", "mechanism": "Upregulated during hypertrophy; mediates pro-inflammatory macrophage activation and fibrosis.", "protein": "Galectin-3 (LGALS3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentia", "gene_name": "LGALS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17931" }, "relationship_type": "causal", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "Released by neutrophils; modulates macrophage polarization and cardiac remodeling.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "regulatory/biomarker", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Myocardial fibrosis", "glycan_involvement": "Glycosylation may regulate secretion and function.", "mechanism": "Promotes macrophage differentiation to proangiogenic phenotype, aiding repair.", "protein": "Annexin A1", "protein_enriched": { "function": "Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a", "gene_name": "ANXA1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P04083" }, "relationship_type": "protective", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Heavily glycosylated; glycan loss may impair function.", "mechanism": "Decreased in EC-lymphatic cells; may affect lymphatic vessel function and cardiac remodeling.", "protein": "Multimerin 1 (MMRN1)", "protein_enriched": { "function": "Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and pl", "gene_name": "MMRN1", "glycan_count": 67, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G27058EU", "G45395BF", "G57776ZS", "G82364UA", "G96881BQ", "G79666IR", "G86880BF", "G90659AW", "G20312EM", "G61806WR", "G70232NH", "G43417UB", "G49108TO", "G11629QQ", "G37881RL", "G80475RE", "G94854LT", "G10819WX", "G22310AV", "G43089EG", "G52527GH", "G56784JY", "G57317CE", "G60145BJ", "G62765YT", "G70441OD", "G75983OB", "G80920RR", "G06247RL", "G27947YN", "G40926MX", "G59626AS", "G60834IK", "G80075MS", "G85554PZ", "G12793SR", "G39595FH", "G57888GL", "G59536GA", "G62461SM", "G93656SY", "G06356OH", "G48414YA", "G10019LZ", "G14669DU", "G28681TP", "G64394MX", "G02030ZB", "G12580WI", "G54992WG", "G83676GD", "G01650EU", "G02815KT", "G04657PL", "G10486CT", "G18647XP", "G28541PG", "G37399XV", "G39446WN", "G47644PP", "G58954YZ", "G63041LO", "G70619PT", "G92050GC", "G57321FI", "G34617SM" ], "uniprot_id": "Q13201" }, "relationship_type": "biomarker", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "N-glycosylation modulates adhesive function.", "mechanism": "Increased signaling in ECs; mediates cell-cell adhesion and vascular integrity.", "protein": "Cadherin-5 (CDH5/VE-cadherin)", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (By similarity). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the so", "gene_name": "CDH5", "glycan_count": 81, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G37881RL", "G66538GV", "G92050GC", "G00273SJ", "G00912UN", "G03644CB", "G04657PL", "G08918WF", "G14972EH", "G20528HD", "G27058EU", "G40834TG", "G43669FQ", "G45395BF", "G77669RF", "G90382BL", "G90659AW", "G92135MA", "G01650EU", "G17208MA", "G18647XP", "G27126ED", "G29184RN", "G29299MO", "G33791AF", "G37399XV", "G41071NU", "G43223CG", "G47644PP", "G47702MW", "G47748JZ", "G59626AS", "G59924QI", "G63041LO", "G70619PT", "G76295SF", "G80475RE", "G83646BJ", "G87661QW", "G94854LT", "G96091TT", "G11629QQ", "G15169WU", "G31433PN", "G39595FH", "G55412XP", "G64527OM", "G69834CE", "G89205CJ", "G22310AV", "G53075ES", "G70232NH", "G80075MS", "G94665LC", "G02030ZB", "G03382KH", "G05610JO", "G05751AZ", "G07097VH", "G08916CY", "G15938BX", "G23294PN", "G23863VK", "G31393GR", "G35226HQ", "G44268RP", "G49108TO", "G51496DK", "G55321QC", "G60230HH", "G61465OY", "G70101JE", "G72667IM", "G75847DX", "G78059CC", "G80920TO", "G81263BG", "G81413UE", "G82463GQ", "G84452RH", "G91636VS" ], "uniprot_id": "P33151" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "N-glycosylation critical for ECM assembly.", "mechanism": "Increased in ECs; facilitates attachment to basement membrane, affects cardiac cell function.", "protein": "Laminin subunit alpha 4 (LAMA4)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Myocardial fibrosis", "glycan_involvement": "Glycosylation regulates ECM interactions.", "mechanism": "Upregulated in fibroblasts during HF; promotes ECM deposition and fibrosis.", "protein": "Fibronectin 1", "relationship_type": "causal", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "N-glycosylation modulates secretion and ECM binding.", "mechanism": "Increased in fibroblast subpopulations; correlates with disease severity and fibrosis.", "protein": "Thrombospondin 4", "protein_enriched": { "function": "Cell adhesion protein that promotes adhesion and outgrowth of hippocampal embryonic neurons. Binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of ", "gene_name": "SPON2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BUD6" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12160080" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "N-glycosylation essential for ECM function.", "mechanism": "Increased in ECs; supports ECM structure and cell adhesion.", "protein": "Laminin subunit gamma 1 (LAMC1)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMC1", "glycan_count": 201, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G06247RL", "G06356OH", "G07755XJ", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G23432EQ", "G23719VF", "G25079LO", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G35029YA", "G39446WN", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43769HG", "G45395BF", "G45504EY", "G46691LC", "G48414YA", "G49955PK", "G50045TK", "G57317CE", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G85554PZ", "G86182NS", "G87661QW", "G90659AW", "G92050GC", "G95177YH", "G95865ZB", "G07246CJ", "G08293MJ", "G20528HD", "G23294PN", "G27126ED", "G30970QQ", "G34730YF", "G35541EV", "G36379GD", "G37509XX", "G40926MX", "G44753VC", "G47644PP", "G57776ZS", "G57888GL", "G64527OM", "G67324HN", "G68490OW", "G70101JE", "G79666IR", "G80479JV", "G85269DF", "G86880BF", "G92135MA", "G92551JA", "G93718GY", "G49108TO", "G11101UV", "G12270AG", "G43417UB", "G53434XO", "G58001LT", "G06110VR", "G05724UK", "G22310AV", "G31028YV", "G33791AF", "G37399XV", "G39188ZX", "G54010QB", "G59924QI", "G62894KT", "G72291OX", "G72747WU", "G74728JK", "G81637OR", "G86795LJ", "G92406TI", "G00273SJ", "G01485JJ", "G02528FI", "G05962QB", "G10819WX", "G11115RO", "G11629QQ", "G13131HA", "G14972EH", "G16125XL", "G20312EM", "G23863VK", "G27947YN", "G28622IK", "G29545VG", "G34617SM", "G37818NZ", "G37995HC", "G39471UU", "G40834TG", "G43669FQ", "G43734MM", "G47950XN", "G49906RN", "G52890YB", "G53075ES", "G55132BD", "G60834IK", "G64394MX", "G69521XL", "G70232NH", "G73968GN", "G80075MS", "G81263BG", "G82443XX", "G85282JO", "G87123QX", "G89045VA", "G90382BL", "G03382KH", "G08290VR", "G10256JP", "G10846ZT", "G11870QZ", "G17208MA", "G23505EP", "G25418HZ", "G25451PN", "G26330YA", "G26759AS", "G44215PV", "G46687AB", "G46902YN", "G47012YE", "G49755GI", "G51640FO", "G52527GH", "G58087IP", "G58954YZ", "G59536GA", "G60177UT", "G63980BQ", "G70375MX", "G72797UR", "G75983OB", "G78787DI", "G80223IX", "G82830MN", "G83229XP", "G87051GH", "G88891KO", "G90093AU", "G91636VS", "G96577RX", "G98611JV", "G03644CB", "G04854VP", "G12341GU", "G13694XX", "G15169WU", "G23010ZW", "G37881RL", "G43089EG", "G59324HL", "G63040RU", "G70888PK", "G76417NN", "G77582RK", "G84225JN", "G92081HT", "G99668VU", "G99679NM", "G57321FI", "G71051TA", "G72398FA" ], "uniprot_id": "P11047" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12160080" }, { "confidence": "high", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "ACE is a glycoprotein; its regulation involves O-GlcNAc modification affecting ER autophagy.", "mechanism": "ACE expression increases with IDD severity; promotes degeneration and senescence of nucleus pulposus (NP) cells.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12160554" }, { "confidence": "high", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Directly catalyzes O-GlcNAc modification of proteins.", "mechanism": "OGT-mediated O-GlcNAcylation increases after ACE knockdown, reducing NP cell degeneration and senescence.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "protective", "source_pmcid": "PMC12160554" }, { "confidence": "high", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Proteoglycan with extensive glycosylation; loss reflects ECM breakdown.", "mechanism": "ACAN expression decreases as IDD progresses; loss indicates matrix degradation.", "protein": "Aggrecan (ACAN)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12160554" }, { "confidence": "high", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Glycosylated protein; loss reflects ECM degeneration.", "mechanism": "COL2A1 expression decreases with IDD; marker of healthy NP matrix.", "protein": "Collagen II (COL2A1)", "protein_enriched": { "function": "Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive f", "gene_name": "COL2A1", "glycan_count": 6, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G31852PQ", "G35541EV", "G62765YT", "G64527OM", "G80920RR", "G49108TO" ], "uniprot_id": "P02458" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12160554" }, { "confidence": "high", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Indirect; PTEN modulates O-GlcNAc modification via ACE regulation.", "mechanism": "PTEN regulates ACE stability via TRIM63-mediated ubiquitination; PTEN knockdown reduces ACE and mitigates NP cell degeneration.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12160554" }, { "confidence": "medium", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Indirect; regulates glycoprotein ACE stability.", "mechanism": "TRIM63 ubiquitinates ACE at K105 (K48 linkage), promoting ACE degradation and influencing IDD progression.", "protein": "TRIM63 (MuRF1)", "protein_enriched": { "function": "E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, ", "gene_name": "TRIM63", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969Q1" }, "relationship_type": "causal", "source_pmcid": "PMC12160554" }, { "confidence": "medium", "disease": "Intervertebral disc degeneration (IDD)", "glycan_involvement": "Removes O-GlcNAc from proteins, modulating glycosylation status.", "mechanism": "OGA inhibition (increased O-GlcNAc) reduces NP cell degeneration; OGA knockdown increases degeneration.", "protein": "O-GlcNAc hydrolase (OGA)", "relationship_type": "causal", "source_pmcid": "PMC12160554" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycoprotein function modulated by glycosylation.", "mechanism": "ACE promotes inflammation via Ang II/AT1R signaling, contributing to tissue degeneration.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal", "source_pmcid": "PMC12160554" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Indirect; regulates glycoprotein degradation.", "mechanism": "TRIM63 is a marker and mediator of muscle atrophy, which is associated with IDD.", "protein": "TRIM63 (MuRF1)", "protein_enriched": { "function": "E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, ", "gene_name": "TRIM63", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969Q1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12160554" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects ACE stability and function.", "mechanism": "ACE is central to RAAS and blood pressure regulation; its dysregulation is linked to hypertension.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12160554" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG trigger CNS demyelination and inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12164171" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation status may influence epitope recognition.", "mechanism": "Detection of anti-MOG antibodies is diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12164171" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation may modulate AQP4 immunogenicity.", "mechanism": "Autoantibodies against AQP4 cause astrocyte damage and demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12164171" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation may affect antibody binding.", "mechanism": "AQP4-IgG seropositivity is diagnostic for NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12164171" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "IgG glycosylation affects anti-inflammatory activity.", "mechanism": "IVIg is used to modulate immune response and treat acute attacks.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12164171" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Glycosylation of IgG influences efficacy.", "mechanism": "IVIg is a mainstay treatment for CIDP.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12164171" }, { "confidence": "medium", "disease": "MG", "glycan_involvement": "IgG glycosylation modulates immune function.", "mechanism": "IVIg used to reduce autoantibody-mediated damage.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12164171" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "Glycosylation may affect antibody specificity.", "mechanism": "Anti-MOG antibodies may be present in NMOSD patients, aiding differential diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12164171" }, { "confidence": "low", "disease": "Autoimmune encephalitis", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "Anti-MOG antibodies can be detected in some autoimmune encephalitis cases.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12164171" }, { "confidence": "low", "disease": "Guillain\u2013Barr\u00e9 syndrome (GBS)", "glycan_involvement": "Potential impact on antibody binding.", "mechanism": "Rarely, anti-MOG antibodies may be detected in GBS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12164171" }, { "confidence": "medium", "disease": "Septic hepatopathy", "glycan_involvement": "Alkaline phosphatase is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated levels indicate cholestatic liver injury in sepsis.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12168498" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Conjugation involves glycosylation-like processes; not a glycoprotein but related.", "mechanism": "Elevated conjugated bilirubin reflects impaired bile flow in septic hepatopathy.", "protein": "Bilirubin (conjugated)", "relationship_type": "biomarker", "source_pmcid": "PMC12168498" }, { "confidence": "medium", "disease": "Septic hepatopathy", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum half-life.", "mechanism": "Elevated AST indicates hepatocellular injury in sepsis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12168498" }, { "confidence": "medium", "disease": "Septic hepatopathy", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence secretion.", "mechanism": "Elevated ALT is a marker of hepatocellular damage in sepsis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12168498" }, { "confidence": "high", "disease": "Severe Dengue", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated AST indicates hepatic injury due to dengue virus infection.", "protein": "Aspartate Aminotransferase (AST/SGOT)", "relationship_type": "biomarker", "source_pmcid": "PMC12168551" }, { "confidence": "high", "disease": "Severe Dengue", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence its secretion and activity.", "mechanism": "Elevated ALT reflects liver cell damage in severe dengue.", "protein": "Alanine Aminotransferase (ALT/SGPT)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scaven", "gene_name": "Got1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05201" }, "relationship_type": "biomarker", "source_pmcid": "PMC12168551" }, { "confidence": "medium", "disease": "Dengue with Warning Signs", "glycan_involvement": "Glycosylation may modulate AST serum half-life.", "mechanism": "Moderately elevated AST is associated with dengue with warning signs.", "protein": "Aspartate Aminotransferase (AST/SGOT)", "relationship_type": "biomarker", "source_pmcid": "PMC12168551" }, { "confidence": "medium", "disease": "Dengue with Warning Signs", "glycan_involvement": "Glycosylation may affect ALT stability.", "mechanism": "Moderately elevated ALT is associated with dengue with warning signs.", "protein": "Alanine Aminotransferase (ALT/SGPT)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scaven", "gene_name": "Got1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05201" }, "relationship_type": "biomarker", "source_pmcid": "PMC12168551" }, { "confidence": "high", "disease": "dystroglycanopathy", "glycan_involvement": "Reduced matriglycan (O-glycosylation) on \u03b1-dystroglycan", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan impairs extracellular matrix binding, destabilizing sarcolemma.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "high", "disease": "dystroglycanopathy", "glycan_involvement": "Impaired glycosylation pathway for matriglycan synthesis", "mechanism": "UGDH variants decrease UDP-glucuronate synthesis, a substrate for \u03b1-dystroglycan glycosylation, leading to hypoglycosylation.", "protein": "UGDH (UDP-glucose dehydrogenase)", "protein_enriched": { "function": "Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, P", "gene_name": "UGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60701" }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "medium", "disease": "epilepsy", "glycan_involvement": "Reduced matriglycan affects neuronal migration and synapse formation", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan disrupts inhibitory synapse development, increasing seizure risk.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "medium", "disease": "epilepsy", "glycan_involvement": "Defective glycosaminoglycan synthesis", "mechanism": "UGDH variants impair GAG synthesis, affecting brain extracellular matrix and neuronal development.", "protein": "UGDH (UDP-glucose dehydrogenase)", "protein_enriched": { "function": "Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, P", "gene_name": "UGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60701" }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "medium", "disease": "intellectual disability", "glycan_involvement": "Loss of matriglycan disrupts laminin binding and pial surface integrity", "mechanism": "Hypoglycosylation leads to neuronal migration errors and synaptic dysfunction.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "medium", "disease": "intellectual disability", "glycan_involvement": "Impaired glycosylation and GAG biosynthesis", "mechanism": "UGDH variants reduce GAG and matriglycan synthesis, affecting brain development.", "protein": "UGDH (UDP-glucose dehydrogenase)", "protein_enriched": { "function": "Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, P", "gene_name": "UGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60701" }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "high", "disease": "hypotonia", "glycan_involvement": "Deficient O-glycosylation (matriglycan)", "mechanism": "Reduced matriglycan weakens muscle cell-matrix interactions, causing muscle weakness.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "medium", "disease": "hypotonia", "glycan_involvement": "Decreased substrate for glycosylation", "mechanism": "UGDH variants impair muscle extracellular matrix remodeling via reduced UDP-glucuronate.", "protein": "UGDH (UDP-glucose dehydrogenase)", "protein_enriched": { "function": "Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, P", "gene_name": "UGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60701" }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "high", "disease": "dystroglycanopathy", "glycan_involvement": "Loss of matriglycan detected by immunostaining and western blot", "mechanism": "Reduced matriglycan immunostaining and low molecular weight \u03b1-dystroglycan are diagnostic for dystroglycanopathy.", "protein": "matriglycan (on \u03b1-dystroglycan)", "relationship_type": "biomarker", "source_pmcid": "PMC12172095" }, { "confidence": "high", "disease": "congenital muscular dystrophy with intellectual disability", "glycan_involvement": "Defective O-glycosylation (matriglycan)", "mechanism": "Abnormal glycosylation (matriglycan deficiency) leads to combined muscle and brain phenotype.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12172095" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N- and O-glycosylation of dystroglycan critical for function; hypoglycosylation leads to disease", "mechanism": "Disrupted dystrophin-glycoprotein complex impairs costamere structure and muscle integrity", "protein": "Dystroglycan (\u03b2-dystroglycan)", "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "high", "disease": "Becker Muscular Dystrophy (BMD)", "glycan_involvement": "Indirect\u2014dystrophin anchors glycosylated dystroglycan", "mechanism": "Partial loss of dystrophin function destabilizes glycoprotein complex, leading to muscle degeneration", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Desminopathy", "glycan_involvement": "Desmin interacts with glycoprotein complexes; glycosylation status may modulate stability", "mechanism": "Mutations disrupt intermediate filament network, impairing muscle structure and function", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Alpha-B crystallin myopathy", "glycan_involvement": "Indirect\u2014chaperones stabilize glycoprotein complexes", "mechanism": "Mutations alter chaperone function, destabilizing desmin and sarcomere structure", "protein": "Alpha B-crystallin", "protein_enriched": { "function": "May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial", "gene_name": "CRYAB", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02511" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Limb Girdle Muscular Dystrophy (LGMD)", "glycan_involvement": "Myotilin interacts with glycoprotein-rich Z-disks", "mechanism": "Mutations cause myotilin aggregation, compromising sarcomere integrity", "protein": "Myotilin", "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "high", "disease": "Limb Girdle Muscular Dystrophy (LGMD2B)", "glycan_involvement": "Dysferlin is a glycoprotein; glycosylation required for membrane localization", "mechanism": "Defective membrane repair due to dysferlin mutations leads to muscle degeneration", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Nemaline Myopathy (NM)", "glycan_involvement": "Potential O-glycosylation modulates protein-protein interactions", "mechanism": "Mutations impair crossbridge cycling and sarcomere function", "protein": "Slow skeletal Myosin Binding Protein-C (sMyBP-C)", "protein_enriched": { "function": "Involved in the regulation of innate immune response. Acts as negative regulator of Toll-like receptor and interferon-regulatory factor (IRF) signaling pathways. Contributes to the negative regulation", "gene_name": "NFKBIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBC1" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Oculopharyngeal Muscular Dystrophy (OPMD)", "glycan_involvement": "Indirect\u2014nuclear protein, but may affect glycoprotein processing", "mechanism": "Expansion mutations cause nuclear aggregates, impairing muscle cell function", "protein": "PABPN1", "protein_enriched": { "function": "Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product (By similarity). Stimulates poly(A) polymerase (PAPOLA) ", "gene_name": "PABPN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U42" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD)", "glycan_involvement": "MEGF10 is a glycoprotein; glycosylation may affect receptor function", "mechanism": "Mutations impair myogenesis and satellite cell function", "protein": "MEGF10", "protein_enriched": { "function": "Receptor for the netrin NTN4 that promotes neuronal cell survival (By similarity). Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration. Plays a role in", "gene_name": "UNC5D", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q6UXZ4" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "medium", "disease": "Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)", "glycan_involvement": "Glycosylation may regulate enzyme stability and secretion", "mechanism": "Loss of enzyme activity leads to toxic metabolite accumulation and GI dysfunction", "protein": "Thymidine phosphorylase", "protein_enriched": { "function": "May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitr", "gene_name": "TYMP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19971" }, "relationship_type": "causal", "source_pmcid": "PMC12181028" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with the muscle membrane glycoprotein complex, which is glycosylated.", "mechanism": "Frameshift mutations in the DMD gene cause truncated dystrophin, leading to loss of membrane stability and muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182250" }, { "confidence": "high", "disease": "Becker Muscular Dystrophy (BMD)", "glycan_involvement": "Partial interaction with glycosylated membrane complexes is retained.", "mechanism": "In-frame mutations in DMD gene produce partially functional dystrophin, resulting in milder phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182250" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Disrupted interaction with glycosylated sarcolemmal proteins.", "mechanism": "Loss of dystrophin function affects cardiac muscle membrane stability, leading to cardiac insufficiency.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182250" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Restored dystrophin can re-establish glycoprotein complex interactions.", "mechanism": "Exon skipping therapies aim to restore dystrophin expression by manipulating mRNA splicing.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12182250" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Functional dystrophin restores glycoprotein complex stability.", "mechanism": "Ataluren promotes read-through of nonsense mutations to produce full-length dystrophin.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12182250" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Detection relies on glycoprotein localization at the sarcolemma.", "mechanism": "Absence or reduction of dystrophin detected by immunohistochemistry is diagnostic for DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12182250" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Loss of glycoprotein complex binding leads to membrane instability.", "mechanism": "Truncated dystrophin lacks cysteine and carboxyl-terminal regions, disrupting interaction with glycoprotein complexes and syntrophins.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182250" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoproteins in the sarcolemma; glycosylation is essential for DGC stability.", "mechanism": "Loss of dystrophin disrupts the dystrophin glycoprotein complex, leading to progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182630" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DGC contains several glycoproteins (e.g., alpha-dystroglycan) whose glycosylation is critical for function.", "mechanism": "Disruption of DGC due to dystrophin deficiency impairs muscle membrane integrity.", "protein": "Dystrophin Glycoprotein Complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Micro-dystrophin integrates into DGC, supporting glycoprotein interactions.", "mechanism": "Gene therapy delivers micro-dystrophin to restore partial function of DGC.", "protein": "Micro-dystrophin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of DGC components in cardiac tissue is affected.", "mechanism": "Dystrophin deficiency leads to cardiac muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Respiratory insufficiency", "glycan_involvement": "Glycoprotein interactions in respiratory muscles are compromised.", "mechanism": "Loss of dystrophin impairs respiratory muscle function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation of alpha-dystroglycan is essential for binding extracellular matrix.", "mechanism": "Defective glycosylation of alpha-dystroglycan impairs DGC function.", "protein": "Alpha-dystroglycan (component of DGC)", "relationship_type": "causal", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Altered glycosylation patterns reflect disease severity.", "mechanism": "DGC integrity and glycosylation status serve as biomarkers for disease progression.", "protein": "Dystrophin Glycoprotein Complex (DGC)", "relationship_type": "biomarker", "source_pmcid": "PMC12182630" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restored dystrophin supports proper glycoprotein complex assembly.", "mechanism": "Restoration of dystrophin expression (via exon skipping, nonsense suppression, gene therapy) slows disease progression.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation of DGC components is required for protective function.", "mechanism": "Intact DGC protects muscle membrane from damage.", "protein": "Dystrophin Glycoprotein Complex (DGC)", "relationship_type": "protective", "source_pmcid": "PMC12182630" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Proper glycosylation of micro-dystrophin is necessary for DGC integration.", "mechanism": "Micro-dystrophin expression levels indicate gene therapy efficacy.", "protein": "Micro-dystrophin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12182630" }, { "confidence": "high", "disease": "Bethlem myopathy", "glycan_involvement": "Defective glycosylation may alter collagen VI assembly and stability.", "mechanism": "Mutations in collagen VI genes impair extracellular matrix integrity, leading to muscle weakness and contractures.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "causal", "source_pmcid": "PMC12185608" }, { "confidence": "high", "disease": "Bethlem myopathy", "glycan_involvement": "N-glycosylation is required for proper folding and secretion.", "mechanism": "Mutations in COL6A1 gene disrupt collagen VI microfibril formation.", "protein": "Collagen VI alpha-1 chain", "relationship_type": "causal", "source_pmcid": "PMC12185608" }, { "confidence": "high", "disease": "Bethlem myopathy", "glycan_involvement": "Altered glycosylation affects protein stability.", "mechanism": "COL6A2 mutations compromise collagen VI network in muscle.", "protein": "Collagen VI alpha-2 chain", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A2", "glycan_count": 115, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G23432EQ", "G25079LO", "G25418HZ", "G28541PG", "G31852PQ", "G31986NC", "G33609NS", "G37412TK", "G39188ZX", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44215PV", "G46503DX", "G48414YA", "G48584BU", "G50045TK", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G65092SV", "G65184UU", "G66766XF", "G70101JE", "G70441OD", "G70619PT", "G72398FA", "G72735IY", "G72787SB", "G72790NZ", "G79568CQ", "G80223IX", "G80920RR", "G82119TF", "G82463GQ", "G82830MN", "G83633GK", "G83646BJ", "G86182NS", "G87661QW", "G98611JV", "G43417UB", "G00273SJ", "G01650EU", "G02030ZB", "G03382KH", "G04657PL", "G05049YU", "G09197ZW", "G11314AS", "G14260UH", "G14994KB", "G16175ZV", "G22310AV", "G22625SJ", "G23863VK", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G29880MM", "G31596VW", "G40664HB", "G40834TG", "G40926MX", "G45395BF", "G46524LG", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G47737VJ", "G49906RN", "G49955PK", "G50073PQ", "G54600FO", "G57776ZS", "G60177UT", "G60923RB", "G66163OV", "G66621EA", "G70375MX", "G72747WU", "G73968GN", "G74430RZ", "G75983OB", "G76295SF", "G79666IR", "G81263BG", "G83229XP", "G83460ZZ", "G84452RH", "G87051GH", "G89098OM", "G90659AW", "G91636VS", "G95177YH", "G96577RX", "G49108TO", "G01485JJ", "G10488MI", "G37509XX" ], "uniprot_id": "P12110" }, "relationship_type": "causal", "source_pmcid": "PMC12185608" }, { "confidence": "high", "disease": "Bethlem myopathy", "glycan_involvement": "Glycosylation modulates chain interactions.", "mechanism": "COL6A3 mutations lead to defective collagen VI assembly.", "protein": "Collagen VI alpha-3 chain", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14031" }, "relationship_type": "causal", "source_pmcid": "PMC12185608" }, { "confidence": "high", "disease": "Ullrich congenital muscular dystrophy", "glycan_involvement": "Aberrant glycosylation exacerbates disease severity.", "mechanism": "Severe mutations in collagen VI genes cause early-onset muscle weakness and joint hypermobility.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "causal", "source_pmcid": "PMC12185608" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "N-glycosylation supports proper folding and membrane localization, enabling shedding.", "mechanism": "Reflects endothelial dysfunction and systemic congestion via increased shedding from stressed endothelium.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "N-glycosylation required for extracellular domain stability and release.", "mechanism": "Elevated levels correlate with clinical and radiographic congestion, independent of myocardial injury.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "N-glycosylation maintains structure for shedding and detection.", "mechanism": "Elevated in HFpEF patients with congestion, even when natriuretic peptides are inconclusive.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation affects circulating stability and renal elimination.", "mechanism": "CKD increases sCD146 via impaired clearance and enhanced endothelial shedding from inflammation.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/confounder", "source_pmcid": "PMC12190286" }, { "confidence": "medium", "disease": "Malignancy", "glycan_involvement": "Glycosylation supports tumor-associated CD146 function and release.", "mechanism": "Elevated in solid tumors due to overexpression and shedding from tumor endothelium.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/confounder", "source_pmcid": "PMC12190286" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "N-glycosylation required for junctional localization and adhesion.", "mechanism": "Loss from endothelial junctions increases vascular permeability and congestion.", "protein": "CD146 (membrane-bound)", "relationship_type": "causal", "source_pmcid": "PMC12190286" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation influences antibody binding and therapeutic targeting.", "mechanism": "Neutralization or inhibition may reduce endothelial hyperpermeability and inflammation.", "protein": "sCD146", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12190286" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Heparan sulfate glycosylation critical for glycocalyx function.", "mechanism": "Elevated levels indicate endothelial glycocalyx degradation and predict adverse outcomes.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation required for secretion and vascular signaling.", "mechanism": "Rises in severe HF and cardiogenic shock, reflecting endothelial activation.", "protein": "Endocan", "protein_enriched": { "function": "Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP", "gene_name": "RANBP3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q9H6Z4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune cell recruitment.", "mechanism": "Elevated during acute decompensation, reflects systemic endothelial inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12190286" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Glycosylation of inhibitors (C-glycosides) enhances binding and stability.", "mechanism": "SGLT1 inhibitors block glucose reabsorption in the intestine/kidney, lowering blood glucose.", "protein": "SGLT1", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a tr", "gene_name": "SLC5A1", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G49108TO" ], "uniprot_id": "P13866" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12190653" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "C-glycosylation of inhibitors is essential for activity and bioavailability.", "mechanism": "SGLT2 inhibitors block renal glucose reabsorption, lowering blood glucose.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Heart disease", "glycan_involvement": "Glycosylation of inhibitors improves pharmacokinetics.", "mechanism": "SGLT1 inhibition reduces cardiac glucose uptake, beneficial in heart failure.", "protein": "SGLT1", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a tr", "gene_name": "SLC5A1", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G49108TO" ], "uniprot_id": "P13866" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Heart disease", "glycan_involvement": "C-glycosylation critical for inhibitor function.", "mechanism": "SGLT2 inhibition reduces cardiac stress and improves outcomes in heart failure.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12190653" }, { "confidence": "high", "disease": "Bacterial infection", "glycan_involvement": "Double C-glycosylation motif essential for activity.", "mechanism": "Acts as an antibiotic against Gram-positive bacteria.", "protein": "Granaticin", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Protozoal infection", "glycan_involvement": "Double C-glycosylation motif confers bioactivity.", "mechanism": "Inhibits protozoal growth.", "protein": "Granaticin", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Leukaemia", "glycan_involvement": "Double C-glycosylation motif required for cytotoxicity.", "mechanism": "Shows activity against P-388 lymphocytic leukaemia in mice.", "protein": "Granaticin", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "high", "disease": "Bacterial infection", "glycan_involvement": "Double C-glycosylation motif critical for antibiotic activity.", "mechanism": "Active against Gram-positive and Gram-negative bacteria.", "protein": "Sarubicin", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Double C-glycosylation motif linked to cytotoxicity.", "mechanism": "Cytotoxic against multiple cancer cell lines.", "protein": "Sarubicinols", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "medium", "disease": "Bacterial infection", "glycan_involvement": "Double C-glycosylation motif required for activity.", "mechanism": "Active against Gram-positive and Gram-negative bacteria.", "protein": "Sch 38519", "relationship_type": "therapeutic", "source_pmcid": "PMC12190653" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Aberrant O-glycosylation exposes tumor-specific epitopes, enhances signaling.", "mechanism": "Overexpression promotes proliferation, invasion, chemoresistance via \u03b2-catenin/EGFR/AKT/BCL-2 pathways.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Increased sialylation (STGal-I), truncated O-glycans (Tn, STn), Siglec-9 interaction.", "mechanism": "Overexpression and altered glycosylation (shorter, sialylated chains) drive tumorigenesis, immune evasion, poor prognosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Loss of O-glycosylated barrier exposes epithelium to inflammation.", "mechanism": "Loss/downregulation increases tumor risk, invasion, poor prognosis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "O-glycosylation stabilizes protein, mediates ligand interactions.", "mechanism": "Overexpression promotes proliferation, metastasis, chemoresistance via HER2/ErbB2/PI3K/FAK pathways.", "protein": "MUC4", "protein_enriched": { "function": "Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces (PubMed:10880978). These g", "gene_name": "MUC4", "glycan_count": 17, "glycosylation_sites_count": 547, "glytoucan_ids": [ "G57321FI", "G00031MO", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G42665KV", "G47325XO", "G49108TO", "G49582PC", "G58272ZE", "G60145BJ", "G63628AV", "G64973KT", "G74722FL", "G76163CP", "G94435QH" ], "uniprot_id": "Q99102" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Heavily O-glycosylated tandem repeats; CA125 epitope is glycan-dependent.", "mechanism": "Upregulation activates PI3K/Akt, EMT, immune evasion; CA125 is diagnostic marker.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Loss of O-glycosylated mucin reduces barrier function.", "mechanism": "Decreased expression correlates with poor prognosis, lymph node metastasis.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Disialyl Lewis a glycan antigen on mucins.", "mechanism": "Elevated serum levels used for diagnosis and prognosis.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Heavily glycosylated; glycan epitopes recognized in assays.", "mechanism": "Serum marker for diagnosis, prognosis, and monitoring.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12191488" }, { "confidence": "medium", "disease": "Cholangiocarcinoma", "glycan_involvement": "O-glycosylation modulates protein-protein interactions.", "mechanism": "Stabilizes \u03b2-catenin, activates Wnt signaling, drives proliferation, invasion, metastasis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12191488" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "O-glycosylated tandem repeats, CA125 epitope.", "mechanism": "Promotes proliferation, metastasis via JAK2/STAT3, Src, FAK; antibody targeting reduces tumor activity.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12191488" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "ZAG is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "ZAG promotes lipolysis and browning of adipose tissue; lower ZAG levels are associated with increased adiposity.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12193239" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation supports ZAG's stability and function in circulation.", "mechanism": "Lower circulating ZAG levels are found in individuals with metabolic syndrome; ZAG negatively correlates with metabolic risk factors.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12193239" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation is essential for ZAG's secretion and systemic effects.", "mechanism": "ZAG levels are negatively correlated with insulin resistance; ZAG has anti-inflammatory effects and stimulates adiponectin.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12193239" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation required for ZAG's function as a circulating adipokine.", "mechanism": "Lower ZAG levels are observed in individuals with type 2 diabetes and dysglycemia.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12193239" }, { "confidence": "medium", "disease": "Metabolic-dysfunction-associated steatotic liver disease", "glycan_involvement": "Glycosylation supports ZAG's hepatic secretion and function.", "mechanism": "ZAG is implicated in hepatic lipid metabolism; altered ZAG may contribute to hepatic steatosis.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12193239" }, { "confidence": "high", "disease": "Cancer cachexia", "glycan_involvement": "Glycosylation is necessary for ZAG's secretion and activity.", "mechanism": "ZAG is overproduced in some tumors and acts as a lipid-mobilizing factor, contributing to cachexia.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12193239" }, { "confidence": "low", "disease": "Proliferative diabetic retinopathy", "glycan_involvement": "Glycosylation required for systemic distribution.", "mechanism": "ZAG is implicated in the pathogenesis of proliferative diabetic retinopathy.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12193239" }, { "confidence": "low", "disease": "Neurocognitive disorders", "glycan_involvement": "Glycosylation supports ZAG's stability and function.", "mechanism": "ZAG has been implicated in the pathogenesis of neurocognitive disorders.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12193239" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation is required for ZAG's biological activity.", "mechanism": "ZAG administration in animal models reduces body weight and promotes lipolysis without affecting lean mass.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12193239" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation is necessary for ZAG's interaction with cell surface receptors.", "mechanism": "ZAG inhibits insulin-induced glucose uptake in adipocytes by impairing insulin signaling at the AKT level.", "protein": "Zinc-alpha2-glycoprotein (ZAG)", "relationship_type": "causal", "source_pmcid": "PMC12193239" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "O-GlcNAc modification of ALDH2 under hyperglycemia reduces its activity, worsening cardiac injury.", "mechanism": "ALDH2*2 variant impairs aldehyde detoxification, increasing oxidative stress, mitochondrial dysfunction, and inflammation, accelerating cardiac fibrosis and dysfunction.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "O-GlcNAc modification may contribute to enzyme dysfunction.", "mechanism": "ALDH2 deficiency increases aldehyde accumulation, oxidative stress, and endothelial dysfunction, raising CAD risk.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "O-GlcNAc modification impairs ALDH2 activity, contributing to heart failure.", "mechanism": "ALDH2*2 carriers have increased cardiac fibrosis and impaired myocardial function due to aldehyde toxicity.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "O-GlcNAc modification reduces ALDH2 activity during ischemia/reperfusion.", "mechanism": "ALDH2*2 variant increases susceptibility to ischemic injury and worsens outcomes after myocardial infarction.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "O-GlcNAc modification may influence ALDH2 function in metabolic tissues.", "mechanism": "ALDH2*2 carriers have higher prevalence of diabetes, possibly due to impaired aldehyde detoxification affecting metabolic regulation.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12193655" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Not directly specified.", "mechanism": "ALDH2*2 carriers with moderate alcohol intake have poorer left atrial function, increasing atrial fibrillation risk.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "medium", "disease": "Upper aerodigestive tract (UADT) cancer", "glycan_involvement": "Not specified.", "mechanism": "ALDH2*2 variant leads to aldehyde accumulation, increasing cancer risk.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "causal", "source_pmcid": "PMC12193655" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "ALDH2*2 mutation associated with increased risk, possibly via aldehyde toxicity.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "risk factor", "source_pmcid": "PMC12193655" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Therapies may counteract O-GlcNAc-induced ALDH2 inhibition.", "mechanism": "ALDH2 activators (e.g., Alda-1, AD-9308) restore enzyme activity, reduce oxidative stress, and improve cardiac function in DCM.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12193655" }, { "confidence": "medium", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Not directly specified.", "mechanism": "SGLT2 inhibitors (e.g., empagliflozin) improve mitochondrial function and reduce oxidative stress, partly by upregulating ALDH2.", "protein": "Aldehyde dehydrogenase 2 (ALDH2)", "protein_enriched": { "function": "Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage", "gene_name": "ALDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05091" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12193655" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Defective N-glycosylation due to impaired mannose-1-phosphate production.", "mechanism": "Loss-of-function mutations in PMM2 disrupt GDP-mannose biosynthesis, impairing N-glycosylation and causing multisystemic disease.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Reduced N-glycosylation due to decreased PMM2 activity.", "mechanism": "Pathogenic missense mutations at dimer interface (e.g., p.Phe119Leu) destabilize PMM2 homodimer, reducing enzyme stability and activity.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Impaired N-glycosylation from loss of enzymatic conversion of mannose-6-phosphate.", "mechanism": "Active site mutation (p.Arg141His) abolishes catalytic activity, leading to glycosylation defects.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Variable N-glycosylation impairment depending on residual PMM2 activity.", "mechanism": "Compound heterozygosity (e.g., p.Arg141His/p.Phe119Leu) leads to partial loss of function, modulating disease severity.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Potential reduction in N-glycosylation due to dimer instability.", "mechanism": "Rare interface variants (e.g., p.Lys115Thr, p.Gly117Arg) predicted to destabilize dimer and may contribute to disease.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "No restoration of N-glycosylation in PMM2-CDG patients.", "mechanism": "PMM1 forms heterodimers with PMM2 in silico, but does not compensate for PMM2 deficiency in vivo.", "protein": "Phosphomannomutase 1 (PMM1)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. In addition, may be responsible for the degradation of glucos", "gene_name": "PMM1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92871" }, "relationship_type": "protective (hypothetical)", "source_pmcid": "PMC12195792" }, { "confidence": "medium", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Enhances N-glycosylation by stabilizing PMM2 structure.", "mechanism": "Glc-1,6-P2 (glucose-1,6-bisphosphate) stabilizes PMM2 dimer and is a potential therapeutic target.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Degree of N-glycosylation defect reflects PMM2 residual activity.", "mechanism": "PMM2 activity and genotype correlate with disease severity and clinical phenotype.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Essential for N-glycosylation; total loss incompatible with life.", "mechanism": "Complete loss of PMM2 activity is lethal; hypomorphic mutations allow survival but cause disease.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type Ia)", "glycan_involvement": "Dimer integrity required for N-glycosylation pathway function.", "mechanism": "Disruption of dimerization interface is a key molecular mechanism in PMM2-CDG pathogenesis.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12195792" }, { "confidence": "high", "disease": "Luminal A breast cancer", "glycan_involvement": "Increased O-glycosylation (core 1, sialyl-T antigen) on MUC1 drives malignant signaling.", "mechanism": "Aberrant O-glycosylation of MUC1 (notably sialyl-T antigen, MUCST) promotes immune evasion and tumor progression.", "protein": "Mucin-1 (MUC1)", "relationship_type": "causal", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Shift from branched core 2 to short, sialylated core 1 O-glycans.", "mechanism": "Overexpression and altered glycosylation of MUC1 is associated with poor prognosis.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Sialyl-T antigen (Neu5Ac\u03b12-3Gal\u03b21-3GalNAc\u03b1-O-Ser/Thr) on MUC1 is key for Siglec-9 interaction.", "mechanism": "MUC1 sialyl-T antigen binds Siglec-9 on macrophages, inducing CXCL5 secretion and tumor-promoting inflammation.", "protein": "Mucin-1 (MUC1)", "relationship_type": "causal", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Upstream regulation by MUC1 O-glycosylation.", "mechanism": "CXCL5 overexpression (induced by MUC1 O-glycans) activates CXCR2, promoting tumor progression, EMT, and immune evasion.", "protein": "CXCL5", "protein_enriched": { "function": "Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes", "gene_name": "CXCL5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42830" }, "relationship_type": "causal", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Catalyzes O-glycosylation (sialylation) of MUC1.", "mechanism": "ST3Gal1 catalyzes MUC1 sialyl-T antigen formation; inhibition reduces tumor-promoting glycoforms and downstream signaling.", "protein": "ST3Gal1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12199699" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Catalyzes O-glycosylation (sialyl-Tn antigen) on MUC1.", "mechanism": "Altered expression affects sialyl-Tn antigen levels, influencing prognosis and invasiveness.", "protein": "ST6GalNAc1", "relationship_type": "biomarker", "source_pmcid": "PMC12199699" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "N- and O-glycosylation (sLe^x epitope).", "mechanism": "Sialyl Lewis-X formation on PSGL-1 modulates leukocyte adhesion and inflammation.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Tumor-associated O-glycans (sialyl-T, sialyl-Tn).", "mechanism": "Aberrant glycosylation of MUC1 is a target for immunotherapy and glycosyltransferase inhibition.", "protein": "Mucin-1 (MUC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Indirectly regulated by MUC1 O-glycosylation.", "mechanism": "CXCL5 levels correlate with poor prognosis, metastasis, and immune suppression.", "protein": "CXCL5", "protein_enriched": { "function": "Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes", "gene_name": "CXCL5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Recognition of sialylated O-glycans on MUC1.", "mechanism": "Siglec-9 on macrophages binds MUC1 sialyl-T antigen, promoting TAM phenotype and tumor progression.", "protein": "Siglec-9", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by c", "gene_name": "SIGLEC9", "glycan_count": 5, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G59626AS", "G95865ZB", "G62765YT", "G11101UV", "G56770VP" ], "uniprot_id": "Q9Y336" }, "relationship_type": "causal", "source_pmcid": "PMC12199699" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "YKL-40 is a secreted glycoprotein; glycosylation is essential for its stability and secretion.", "mechanism": "Elevated CSF YKL-40 is associated with neuroinflammation and increased AD risk.", "protein": "Chitinase-3-like protein 1 (YKL-40)", "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Tau is O-glycosylated; glycosylation may affect aggregation and pathology.", "mechanism": "Elevated CSF tau reflects neurodegeneration and AD pathology.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its stability and function.", "mechanism": "Increased plasma CRP indicates chronic peripheral inflammation, which is linked to AD risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased AD risk, especially in APOE \u03b54 carriers.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation is required for YKL-40 secretion and function.", "mechanism": "YKL-40 is upregulated in neuroinflammatory states.", "protein": "Chitinase-3-like protein 1 (YKL-40)", "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "O-glycosylation may modulate tau phosphorylation and aggregation.", "mechanism": "CSF ptau reflects tau pathology and neurodegeneration in AD.", "protein": "Phosphorylated tau (ptau)", "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "A\u03b2 peptides are derived from APP, a glycoprotein; glycosylation affects APP processing.", "mechanism": "CSF A\u03b242 is a core biomarker for amyloid pathology in AD.", "protein": "Amyloid-beta 42 (A\u03b242)", "protein_enriched": { "function": "", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05067-4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation is important for receptor function.", "mechanism": "CSF sTREM2 reflects microglial activation in AD.", "protein": "Soluble TREM2 (sTREM2)", "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Derived from glycosylated APP; glycosylation influences peptide generation.", "mechanism": "CSF A\u03b240/A\u03b242 ratio is used to assess amyloid pathology.", "protein": "Amyloid-beta 40 (A\u03b240)", "protein_enriched": { "function": "", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05067-3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation is essential for CRP's structure and function.", "mechanism": "CRP is a marker of systemic inflammation that may contribute to neuroinflammatory processes.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12203597" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "GlycA signal arises from N-acetyl methyl groups on N-glycans of acute-phase glycoproteins.", "mechanism": "GlycA reflects the concentration of circulating acute-phase glycoproteins, serving as a stable marker of systemic inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Non-communicable diseases (NCDs)", "glycan_involvement": "N-glycosylation of acute-phase proteins contributes to GlycA signal.", "mechanism": "Elevated GlycA is associated with increased risk of NCDs due to its reflection of chronic inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "CRP is N-glycosylated, which may affect its stability and function.", "mechanism": "CRP is a classical acute-phase reactant elevated during systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation may modulate CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased cardiovascular risk, reflecting underlying inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycans on acute-phase glycoproteins contribute to GlycA signal.", "mechanism": "Higher GlycA levels are linked to increased cardiovascular risk, reflecting chronic inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "N-glycosylation of acute-phase proteins is essential for GlycA measurement.", "mechanism": "GlycA is a stable marker of chronic low-grade inflammation, more so than CRP.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "IL-6 is glycosylated, which may affect its secretion and activity.", "mechanism": "IL-6 is a cytokine elevated in systemic inflammation and regulates acute-phase protein production.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Non-communicable diseases (NCDs)", "glycan_involvement": "GlycA reflects N-glycan modifications on acute-phase proteins.", "mechanism": "Genetic and cohort analyses suggest PUFAs increase GlycA, which is linked to NCD risk.", "protein": "GlycA", "relationship_type": "causal", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Non-communicable diseases (NCDs)", "glycan_involvement": "N-glycosylation may influence CRP's role in disease.", "mechanism": "CRP is elevated in chronic inflammatory states associated with NCDs.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12204398" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation of acute-phase proteins is central to GlycA signal.", "mechanism": "Mendelian randomization suggests n-6 PUFAs causally increase GlycA, indicating a role in promoting inflammation.", "protein": "GlycA", "relationship_type": "causal", "source_pmcid": "PMC12204398" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Kir4.2 is N-glycosylated; glycosylation affects stability and trafficking, but R28C mutation does not alter glycosylation pattern.", "mechanism": "Loss-of-function R28C mutation leads to impaired channel activity, reduced protein stability, and defective plasma membrane trafficking, disrupting K+ homeostasis and increasing neuronal excitability.", "protein": "Kir4.2 (KCNJ15)", "protein_enriched": { "function": "K(+) channel subunit that may homo- and heterodimerize to form functional channels with distinct regulatory and gating properties. Can heterodimerize with KCNK13 subunit to conduct K(+) outward rectif", "gene_name": "KCNK12", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HB15" }, "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation may be leveraged to modulate channel stability/trafficking.", "mechanism": "Kir4.2 dysfunction implicated in PD pathogenesis; targeting its stability or degradation pathways may offer therapeutic benefit.", "protein": "Kir4.2 (KCNJ15)", "protein_enriched": { "function": "K(+) channel subunit that may homo- and heterodimerize to form functional channels with distinct regulatory and gating properties. Can heterodimerize with KCNK13 subunit to conduct K(+) outward rectif", "gene_name": "KCNK12", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HB15" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12206441" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Not directly addressed.", "mechanism": "KCNJ15 gene associated with AD in GWAS; highly expressed in immune system, involved in immune-related events.", "protein": "Kir4.2 (KCNJ15)", "protein_enriched": { "function": "K(+) channel subunit that may homo- and heterodimerize to form functional channels with distinct regulatory and gating properties. Can heterodimerize with KCNK13 subunit to conduct K(+) outward rectif", "gene_name": "KCNK12", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HB15" }, "relationship_type": "biomarker", "source_pmcid": "PMC12206441" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Not specified.", "mechanism": "G156S mutation in GIRK2 causes loss of K+ selectivity, leading to excitotoxicity and neurodegeneration in mouse PD models.", "protein": "Kir3.2 (GIRK2)", "protein_enriched": { "function": "Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration o", "gene_name": "Kcnj6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48542" }, "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "Not specified.", "mechanism": "Kir4.2 implicated in epilepsy via regulation of neuronal excitability.", "protein": "Kir4.2 (KCNJ15)", "protein_enriched": { "function": "K(+) channel subunit that may homo- and heterodimerize to form functional channels with distinct regulatory and gating properties. Can heterodimerize with KCNK13 subunit to conduct K(+) outward rectif", "gene_name": "KCNK12", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HB15" }, "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "N-glycosylation affects CFTR folding and trafficking.", "mechanism": "\u0394F508 mutation disrupts folding and maturation, leading to loss of function.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Not specified.", "mechanism": "N-terminal mutations disrupt Golgi export and membrane expression, potentially contributing to disease.", "protein": "Kir4.1", "protein_enriched": { "function": "May be responsible for potassium buffering action of glial cells in the brain (By similarity). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow in", "gene_name": "KCNJ10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P78508" }, "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Not specified.", "mechanism": "Used as a plasma membrane marker in studies of Kir4.2 trafficking.", "protein": "Na+/K+ ATPase", "protein_enriched": { "function": "This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the e", "gene_name": "ATP1A1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G36379GD", "G49108TO" ], "uniprot_id": "P05023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12206441" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation status may aid in detection.", "mechanism": "Kir4.2 R28C mutation segregates with familial PD; potential for use as a genetic biomarker.", "protein": "Kir4.2 (KCNJ15)", "protein_enriched": { "function": "K(+) channel subunit that may homo- and heterodimerize to form functional channels with distinct regulatory and gating properties. Can heterodimerize with KCNK13 subunit to conduct K(+) outward rectif", "gene_name": "KCNK12", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HB15" }, "relationship_type": "biomarker", "source_pmcid": "PMC12206441" }, { "confidence": "low", "disease": "Brugada syndrome", "glycan_involvement": "Not specified.", "mechanism": "R104W mutation in N-terminus abolishes Na+ currents, causing arrhythmia.", "protein": "Nav1.5", "relationship_type": "causal", "source_pmcid": "PMC12206441" }, { "confidence": "high", "disease": "PMM2-congenital disorder of glycosylation (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation due to PMM2 mutation", "mechanism": "PMM2 deficiency impairs N-glycosylation of multiple glycoproteins", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "Impaired N-glycosylation affects secretion and function", "mechanism": "Hypoglycosylation leads to reduced activity and stability of coagulation factors", "protein": "Coagulation factors", "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "high", "disease": "Thrombophilia", "glycan_involvement": "N-glycosylation required for stability and plasma half-life", "mechanism": "Glycosylation defects reduce antithrombin III levels, increasing thrombosis risk", "protein": "Antithrombin III", "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "high", "disease": "Venous thrombosis", "glycan_involvement": "N-glycosylation essential for secretion and function", "mechanism": "Hypoglycosylation lowers protein C activity, promoting thrombosis", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "high", "disease": "Venous thrombosis", "glycan_involvement": "N-glycosylation affects plasma stability", "mechanism": "Defective glycosylation decreases protein S levels, increasing thrombotic risk", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "high", "disease": "PMM2-congenital disorder of glycosylation (PMM2-CDG)", "glycan_involvement": "Altered N-glycosylation detected by isoelectric focusing", "mechanism": "Isoform pattern of transferrin reflects glycosylation status", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210067" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "N-glycosylation required for antibody stability and effector function", "mechanism": "Hypoglycosylation impairs immunoglobulin function and immune response", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "medium", "disease": "Hemorrhage", "glycan_involvement": "N-glycosylation affects multimerization and function", "mechanism": "Defective glycosylation reduces VWF activity, increasing bleeding risk", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation required for secretion and polymerization", "mechanism": "Hypoglycosylation impairs fibrinogen function in clot formation", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "medium", "disease": "Infection susceptibility", "glycan_involvement": "N-glycosylation required for complement activation", "mechanism": "Glycosylation defects reduce complement activity, increasing infection risk", "protein": "Complement proteins", "relationship_type": "causal", "source_pmcid": "PMC12210067" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Ceruloplasmin levels are measured to assess liver synthetic function.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin glycosylation may be altered in liver disease, affecting function.", "mechanism": "Hypoalbuminemia reflects impaired hepatic synthesis in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Cholinesterase glycosylation is important for secretion and activity.", "mechanism": "Decreased cholinesterase indicates reduced liver synthetic capacity.", "protein": "Cholinesterase", "protein_enriched": { "function": "Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters", "gene_name": "BCHE", "glycan_count": 40, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G00912UN", "G01650EU", "G11314AS", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G37881RL", "G40574BA", "G41247ZX", "G59626AS", "G62765YT", "G80920RR", "G83646BJ", "G86795LJ", "G95865ZB", "G43089EG", "G70441OD", "G08918WF", "G27058EU", "G43223CG", "G11629QQ", "G12270AG", "G13694XX", "G15169WU", "G48414YA", "G55412XP", "G62461SM", "G81263BG", "G84452RH", "G28465XX", "G06247RL", "G27947YN", "G42466VF", "G45395BF", "G70232NH", "G70619PT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P06276" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "medium", "disease": "Pancreatic fat infiltration", "glycan_involvement": "Elastase-1 is glycosylated; glycosylation affects enzyme stability.", "mechanism": "Low elastase-1 in stool indicates exocrine pancreatic insufficiency.", "protein": "Elastase-1", "protein_enriched": { "function": "Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion an", "gene_name": "CELA2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08217" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "low", "disease": "Shwachman-Diamond syndrome (SDS)", "glycan_involvement": "Glycosylation status may affect diagnostic accuracy.", "mechanism": "Ceruloplasmin levels help exclude Wilson disease in differential diagnosis of SDS.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "high", "disease": "Ascites", "glycan_involvement": "Glycosylation may affect albumin's oncotic properties.", "mechanism": "Albumin correction is used to treat hypoalbuminemia and resolve ascites.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12210156" }, { "confidence": "medium", "disease": "Shwachman-Diamond syndrome (SDS)", "glycan_involvement": "Altered glycosylation may reflect disease severity.", "mechanism": "Low albumin is a marker of SDS-related liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "medium", "disease": "Shwachman-Diamond syndrome (SDS)", "glycan_involvement": "Glycosylation impacts enzyme activity and secretion.", "mechanism": "Low cholinesterase is indicative of SDS-related liver impairment.", "protein": "Cholinesterase", "protein_enriched": { "function": "Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters", "gene_name": "BCHE", "glycan_count": 40, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G00912UN", "G01650EU", "G11314AS", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G37881RL", "G40574BA", "G41247ZX", "G59626AS", "G62765YT", "G80920RR", "G83646BJ", "G86795LJ", "G95865ZB", "G43089EG", "G70441OD", "G08918WF", "G27058EU", "G43223CG", "G11629QQ", "G12270AG", "G13694XX", "G15169WU", "G48414YA", "G55412XP", "G62461SM", "G81263BG", "G84452RH", "G28465XX", "G06247RL", "G27947YN", "G42466VF", "G45395BF", "G70232NH", "G70619PT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P06276" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "medium", "disease": "Shwachman-Diamond syndrome (SDS)", "glycan_involvement": "Glycosylation affects enzyme stability and detection.", "mechanism": "Low elastase-1 reflects exocrine pancreatic insufficiency in SDS.", "protein": "Elastase-1", "protein_enriched": { "function": "Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion an", "gene_name": "CELA2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08217" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "low", "disease": "Pancytopenia", "glycan_involvement": "Glycosylation changes may correlate with hematological status.", "mechanism": "Hypoalbuminemia may be associated with bone marrow dysfunction in SDS.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210156" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "Elevated ALT levels indicate hepatocellular injury and correlate with NAFLD severity.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "AST glycosylation modulates its secretion and activity.", "mechanism": "Elevated AST levels reflect liver inflammation and injury in NAFLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation influences its enzymatic activity.", "mechanism": "Increased GGT is associated with oxidative stress and liver dysfunction in NAFLD.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation may affect ALT serum detection.", "mechanism": "ALT levels >2x normal are used to diagnose NASH per guidelines.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation impacts AST stability and detection.", "mechanism": "AST elevation (>2x) is a marker for NASH diagnosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation modulates GGT activity and serum levels.", "mechanism": "GGT elevation (>2x) is a marker for NASH diagnosis.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "PPC increases membrane phosphatidylcholine, indirectly affecting glycoprotein function.", "mechanism": "PPC supplementation improves liver enzyme levels and ultrasonography features in NAFLD.", "protein": "PPC (Essentiale)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12210169" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Restores membrane lipid/glycoprotein balance, reducing oxidative stress.", "mechanism": "PPC reduces liver inflammation and improves enzyme profiles in NASH.", "protein": "PPC (Essentiale)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12210169" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation status may change with disease progression.", "mechanism": "Elevated enzymes are associated with progression to fibrosis.", "protein": "ALT/AST/GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation may reflect advanced liver disease.", "mechanism": "Persistent elevation indicates risk for cirrhosis.", "protein": "ALT/AST/GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12210169" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation pattern of M2BP is altered in fibrosis, increasing its diagnostic value.", "mechanism": "Serum glycosylated M2BP levels correlate with liver fibrosis severity.", "protein": "Mac-2 binding protein (M2BP)", "protein_enriched": { "function": "Promotes integrin-mediated cell adhesion. May stimulate host defense against viruses and tumor cells", "gene_name": "LGALS3BP", "glycan_count": 222, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G05962QB", "G06247RL", "G07246CJ", "G08290VR", "G08918WF", "G11314AS", "G11870QZ", "G13131HA", "G14669DU", "G14972EH", "G16125XL", "G23719VF", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G31852PQ", "G32926LW", "G36379GD", "G37995HC", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G47644PP", "G50856PC", "G53075ES", "G57776ZS", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G70232NH", "G70441OD", "G74724QE", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83633GK", "G85282JO", "G85554PZ", "G92050GC", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G13694XX", "G37399XV", "G37881RL", "G62461SM", "G01160VV", "G03644CB", "G05724UK", "G10019LZ", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G24377DY", "G29545VG", "G30221QT", "G32788FZ", "G35541EV", "G39595FH", "G40926MX", "G41044JW", "G44753VC", "G45526EA", "G47518TP", "G48414YA", "G52527GH", "G57888GL", "G59626AS", "G60834IK", "G64394MX", "G68490OW", "G69834CE", "G70888PK", "G74381CZ", "G76295SF", "G81263BG", "G81637OR", "G83460ZZ", "G85144OK", "G86795LJ", "G86880BF", "G87123QX", "G87399DK", "G87661QW", "G88374WZ", "G90659AW", "G93656SY", "G94917XT", "G95678HJ", "G96577RX", "G57321FI", "G43417UB", "G49108TO", "G01650EU", "G02528FI", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G08293MJ", "G10486CT", "G10819WX", "G11101UV", "G14260UH", "G15127JD", "G18647XP", "G20210JR", "G20425TQ", "G20528HD", "G22140GZ", "G22572EH", "G23294PN", "G23863VK", "G25451PN", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G30970QQ", "G33791AF", "G34617SM", "G35107SO", "G37509XX", "G37692EO", "G37868ZX", "G39188ZX", "G39446WN", "G41126SR", "G41840AI", "G42962KI", "G43089EG", "G43669FQ", "G44215PV", "G45495MK", "G45504EY", "G46691LC", "G49018RC", "G49755GI", "G49906RN", "G50045TK", "G51640FO", "G51653BI", "G55132BD", "G56770VP", "G57776ZU", "G57818FI", "G59536GA", "G59924QI", "G60033FS", "G62837OZ", "G63040RU", "G63041LO", "G64751KD", "G65184UU", "G66163OV", "G66676MI", "G69521XL", "G70619PT", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G72791KH", "G72797UR", "G75568BH", "G75983OB", "G77459ND", "G80966KZ", "G82020ZR", "G82443XX", "G83555HU", "G83646BJ", "G84452RH", "G84820NF", "G90093AU", "G92406TI", "G95046LV", "G99660SU", "G99668VU", "G99679NM", "G01937VC", "G40834TG", "G12313PD", "G14994KB", "G23505EP", "G26271XI", "G29299MO", "G37818NZ", "G39471UU", "G46524LG", "G47950XN", "G49739MP", "G51413EV", "G55412XP", "G56518TU", "G56784JY", "G57317CE", "G66760KM", "G71146HJ", "G71463BG", "G71784JC", "G73686WG", "G82463GQ", "G85269DF", "G90382BL" ], "uniprot_id": "Q08380" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210174" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Altered glycosylation enhances M2BP detection in MASLD.", "mechanism": "Glycosylated M2BP is proposed as a non-invasive marker for MASLD staging.", "protein": "Mac-2 binding protein (M2BP)", "protein_enriched": { "function": "Promotes integrin-mediated cell adhesion. May stimulate host defense against viruses and tumor cells", "gene_name": "LGALS3BP", "glycan_count": 222, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G05962QB", "G06247RL", "G07246CJ", "G08290VR", "G08918WF", "G11314AS", "G11870QZ", "G13131HA", "G14669DU", "G14972EH", "G16125XL", "G23719VF", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G31852PQ", "G32926LW", "G36379GD", "G37995HC", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G47644PP", "G50856PC", "G53075ES", "G57776ZS", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G70232NH", "G70441OD", "G74724QE", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83633GK", "G85282JO", "G85554PZ", "G92050GC", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G13694XX", "G37399XV", "G37881RL", "G62461SM", "G01160VV", "G03644CB", "G05724UK", "G10019LZ", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G24377DY", "G29545VG", "G30221QT", "G32788FZ", "G35541EV", "G39595FH", "G40926MX", "G41044JW", "G44753VC", "G45526EA", "G47518TP", "G48414YA", "G52527GH", "G57888GL", "G59626AS", "G60834IK", "G64394MX", "G68490OW", "G69834CE", "G70888PK", "G74381CZ", "G76295SF", "G81263BG", "G81637OR", "G83460ZZ", "G85144OK", "G86795LJ", "G86880BF", "G87123QX", "G87399DK", "G87661QW", "G88374WZ", "G90659AW", "G93656SY", "G94917XT", "G95678HJ", "G96577RX", "G57321FI", "G43417UB", "G49108TO", "G01650EU", "G02528FI", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G08293MJ", "G10486CT", "G10819WX", "G11101UV", "G14260UH", "G15127JD", "G18647XP", "G20210JR", "G20425TQ", "G20528HD", "G22140GZ", "G22572EH", "G23294PN", "G23863VK", "G25451PN", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G30970QQ", "G33791AF", "G34617SM", "G35107SO", "G37509XX", "G37692EO", "G37868ZX", "G39188ZX", "G39446WN", "G41126SR", "G41840AI", "G42962KI", "G43089EG", "G43669FQ", "G44215PV", "G45495MK", "G45504EY", "G46691LC", "G49018RC", "G49755GI", "G49906RN", "G50045TK", "G51640FO", "G51653BI", "G55132BD", "G56770VP", "G57776ZU", "G57818FI", "G59536GA", "G59924QI", "G60033FS", "G62837OZ", "G63040RU", "G63041LO", "G64751KD", "G65184UU", "G66163OV", "G66676MI", "G69521XL", "G70619PT", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G72791KH", "G72797UR", "G75568BH", "G75983OB", "G77459ND", "G80966KZ", "G82020ZR", "G82443XX", "G83555HU", "G83646BJ", "G84452RH", "G84820NF", "G90093AU", "G92406TI", "G95046LV", "G99660SU", "G99668VU", "G99679NM", "G01937VC", "G40834TG", "G12313PD", "G14994KB", "G23505EP", "G26271XI", "G29299MO", "G37818NZ", "G39471UU", "G46524LG", "G47950XN", "G49739MP", "G51413EV", "G55412XP", "G56518TU", "G56784JY", "G57317CE", "G66760KM", "G71146HJ", "G71463BG", "G71784JC", "G73686WG", "G82463GQ", "G85269DF", "G90382BL" ], "uniprot_id": "Q08380" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210174" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Disease-specific glycan modifications increase M2BP serum levels.", "mechanism": "Elevated glycosylated M2BP levels are associated with cirrhosis progression.", "protein": "Mac-2 binding protein (M2BP)", "protein_enriched": { "function": "Promotes integrin-mediated cell adhesion. May stimulate host defense against viruses and tumor cells", "gene_name": "LGALS3BP", "glycan_count": 222, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G05962QB", "G06247RL", "G07246CJ", "G08290VR", "G08918WF", "G11314AS", "G11870QZ", "G13131HA", "G14669DU", "G14972EH", "G16125XL", "G23719VF", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G31852PQ", "G32926LW", "G36379GD", "G37995HC", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G47644PP", "G50856PC", "G53075ES", "G57776ZS", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G70232NH", "G70441OD", "G74724QE", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83633GK", "G85282JO", "G85554PZ", "G92050GC", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G13694XX", "G37399XV", "G37881RL", "G62461SM", "G01160VV", "G03644CB", "G05724UK", "G10019LZ", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G24377DY", "G29545VG", "G30221QT", "G32788FZ", "G35541EV", "G39595FH", "G40926MX", "G41044JW", "G44753VC", "G45526EA", "G47518TP", "G48414YA", "G52527GH", "G57888GL", "G59626AS", "G60834IK", "G64394MX", "G68490OW", "G69834CE", "G70888PK", "G74381CZ", "G76295SF", "G81263BG", "G81637OR", "G83460ZZ", "G85144OK", "G86795LJ", "G86880BF", "G87123QX", "G87399DK", "G87661QW", "G88374WZ", "G90659AW", "G93656SY", "G94917XT", "G95678HJ", "G96577RX", "G57321FI", "G43417UB", "G49108TO", "G01650EU", "G02528FI", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G08293MJ", "G10486CT", "G10819WX", "G11101UV", "G14260UH", "G15127JD", "G18647XP", "G20210JR", "G20425TQ", "G20528HD", "G22140GZ", "G22572EH", "G23294PN", "G23863VK", "G25451PN", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G30970QQ", "G33791AF", "G34617SM", "G35107SO", "G37509XX", "G37692EO", "G37868ZX", "G39188ZX", "G39446WN", "G41126SR", "G41840AI", "G42962KI", "G43089EG", "G43669FQ", "G44215PV", "G45495MK", "G45504EY", "G46691LC", "G49018RC", "G49755GI", "G49906RN", "G50045TK", "G51640FO", "G51653BI", "G55132BD", "G56770VP", "G57776ZU", "G57818FI", "G59536GA", "G59924QI", "G60033FS", "G62837OZ", "G63040RU", "G63041LO", "G64751KD", "G65184UU", "G66163OV", "G66676MI", "G69521XL", "G70619PT", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G72791KH", "G72797UR", "G75568BH", "G75983OB", "G77459ND", "G80966KZ", "G82020ZR", "G82443XX", "G83555HU", "G83646BJ", "G84452RH", "G84820NF", "G90093AU", "G92406TI", "G95046LV", "G99660SU", "G99668VU", "G99679NM", "G01937VC", "G40834TG", "G12313PD", "G14994KB", "G23505EP", "G26271XI", "G29299MO", "G37818NZ", "G39471UU", "G46524LG", "G47950XN", "G49739MP", "G51413EV", "G55412XP", "G56518TU", "G56784JY", "G57317CE", "G66760KM", "G71146HJ", "G71463BG", "G71784JC", "G73686WG", "G82463GQ", "G85269DF", "G90382BL" ], "uniprot_id": "Q08380" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210174" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation changes in M2BP reflect malignant transformation.", "mechanism": "Glycosylated M2BP may help identify HCC risk in patients with advanced liver disease.", "protein": "Mac-2 binding protein (M2BP)", "protein_enriched": { "function": "Promotes integrin-mediated cell adhesion. May stimulate host defense against viruses and tumor cells", "gene_name": "LGALS3BP", "glycan_count": 222, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G05962QB", "G06247RL", "G07246CJ", "G08290VR", "G08918WF", "G11314AS", "G11870QZ", "G13131HA", "G14669DU", "G14972EH", "G16125XL", "G23719VF", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G31852PQ", "G32926LW", "G36379GD", "G37995HC", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G47644PP", "G50856PC", "G53075ES", "G57776ZS", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G70232NH", "G70441OD", "G74724QE", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83633GK", "G85282JO", "G85554PZ", "G92050GC", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G13694XX", "G37399XV", "G37881RL", "G62461SM", "G01160VV", "G03644CB", "G05724UK", "G10019LZ", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G24377DY", "G29545VG", "G30221QT", "G32788FZ", "G35541EV", "G39595FH", "G40926MX", "G41044JW", "G44753VC", "G45526EA", "G47518TP", "G48414YA", "G52527GH", "G57888GL", "G59626AS", "G60834IK", "G64394MX", "G68490OW", "G69834CE", "G70888PK", "G74381CZ", "G76295SF", "G81263BG", "G81637OR", "G83460ZZ", "G85144OK", "G86795LJ", "G86880BF", "G87123QX", "G87399DK", "G87661QW", "G88374WZ", "G90659AW", "G93656SY", "G94917XT", "G95678HJ", "G96577RX", "G57321FI", "G43417UB", "G49108TO", "G01650EU", "G02528FI", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G08293MJ", "G10486CT", "G10819WX", "G11101UV", "G14260UH", "G15127JD", "G18647XP", "G20210JR", "G20425TQ", "G20528HD", "G22140GZ", "G22572EH", "G23294PN", "G23863VK", "G25451PN", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G30970QQ", "G33791AF", "G34617SM", "G35107SO", "G37509XX", "G37692EO", "G37868ZX", "G39188ZX", "G39446WN", "G41126SR", "G41840AI", "G42962KI", "G43089EG", "G43669FQ", "G44215PV", "G45495MK", "G45504EY", "G46691LC", "G49018RC", "G49755GI", "G49906RN", "G50045TK", "G51640FO", "G51653BI", "G55132BD", "G56770VP", "G57776ZU", "G57818FI", "G59536GA", "G59924QI", "G60033FS", "G62837OZ", "G63040RU", "G63041LO", "G64751KD", "G65184UU", "G66163OV", "G66676MI", "G69521XL", "G70619PT", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G72791KH", "G72797UR", "G75568BH", "G75983OB", "G77459ND", "G80966KZ", "G82020ZR", "G82443XX", "G83555HU", "G83646BJ", "G84452RH", "G84820NF", "G90093AU", "G92406TI", "G95046LV", "G99660SU", "G99668VU", "G99679NM", "G01937VC", "G40834TG", "G12313PD", "G14994KB", "G23505EP", "G26271XI", "G29299MO", "G37818NZ", "G39471UU", "G46524LG", "G47950XN", "G49739MP", "G51413EV", "G55412XP", "G56518TU", "G56784JY", "G57317CE", "G66760KM", "G71146HJ", "G71463BG", "G71784JC", "G73686WG", "G82463GQ", "G85269DF", "G90382BL" ], "uniprot_id": "Q08380" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210174" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GCG is a glycoprotein; glycosylation may affect stability and receptor interaction, but not directly discussed.", "mechanism": "Elevated fasting GCG is associated with increased risk and severity of MASLD in T2DM patients, possibly due to hepatic GCG resistance and feedback elevation.", "protein": "Glucagon (GCG)", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "GCG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Glycosylation may modulate GCG secretion and activity; not directly discussed.", "mechanism": "GCG dysregulation contributes to hyperglycemia and metabolic imbalance in T2DM.", "protein": "Glucagon (GCG)", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "GCG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01275" }, "relationship_type": "causal", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "GCG glycosylation may affect clearance; not directly discussed.", "mechanism": "Hyperglucagonemia is observed in chronic liver diseases including cirrhosis.", "protein": "Glucagon (GCG)", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "GCG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CP is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Elevated fasting CP is associated with increased risk of MASLD in T2DM, reflecting insulin resistance and hepatic lipid dysregulation.", "protein": "C-peptide (CP)", "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "CP glycosylation may influence its metabolic effects.", "mechanism": "Fasting CP is positively associated with NASH and liver fibrosis in T2DM and obese patients.", "protein": "C-peptide (CP)", "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "INS is glycosylated; glycosylation affects receptor binding and clearance.", "mechanism": "Elevated fasting insulin and insulin resistance are correlated with MASLD severity.", "protein": "Insulin (INS)", "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Glycosylation may modulate GCG activity.", "mechanism": "GCG resistance and hyperglucagonemia are implicated in progression from steatosis to NASH.", "protein": "Glucagon (GCG)", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "GCG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Glycosylation affects CP stability.", "mechanism": "CP levels reflect endogenous insulin secretion and are elevated in T2DM with MASLD.", "protein": "C-peptide (CP)", "relationship_type": "biomarker", "source_pmcid": "PMC12210176" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect pharmacokinetics of GCG agonists.", "mechanism": "GCG agonists are being explored as novel treatments for MASLD and T2DM.", "protein": "Glucagon (GCG)", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "GCG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12210176" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Glycosylation modulates insulin receptor interaction.", "mechanism": "Insulin resistance is central to T2DM and MASLD pathogenesis.", "protein": "Insulin (INS)", "relationship_type": "causal", "source_pmcid": "PMC12210176" }, { "confidence": "high", "disease": "Gynecomastia (GYN)", "glycan_involvement": "E2 is transported by glycoprotein SHBG; glycosylation affects E2 bioavailability.", "mechanism": "Elevated E2 stimulates breast tissue proliferation via estrogen receptor activation.", "protein": "Estradiol (E2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "SHBG glycosylation modulates hormone binding and serum half-life.", "mechanism": "Increased SHBG reduces free testosterone, increasing E2/T ratio and risk of GYN.", "protein": "Sex Hormone-Binding Globulin (SHBG)", "protein_enriched": { "function": "Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, a", "gene_name": "SHBG", "glycan_count": 23, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01614ZM", "G43417UB", "G56682BC", "G65562ZE", "G74722FL", "G81006GJ", "G00912UN", "G06356OH", "G37320GX", "G40574BA", "G45395BF", "G48414YA", "G56749GV", "G59626AS", "G69062KW", "G81413UE", "G82830MN", "G84467IZ", "G87433AX", "G04854VP", "G77669RF", "G94470IW", "G22310AV" ], "uniprot_id": "P04278" }, "relationship_type": "causal", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "Aromatase is glycosylated, affecting enzyme stability and activity.", "mechanism": "Increased aromatase activity in adipose tissue converts androgens to estrogens, raising E2.", "protein": "Aromatase (CYP19A1)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (P", "gene_name": "CYP19A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11511" }, "relationship_type": "causal", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "ER\u03b1 glycosylation modulates receptor signaling and ligand binding.", "mechanism": "ER\u03b1 mediates E2-induced proliferation of mammary epithelial cells.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "AR glycosylation may affect receptor function and tissue localization.", "mechanism": "AR inhibits breast tissue proliferation; reduced AR activity increases GYN risk.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "protective", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "IL-6 glycosylation affects cytokine stability and receptor interaction.", "mechanism": "IL-6 promotes aromatase activity, increasing local estrogen production in breast tissue.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Gynecomastia (GYN)", "glycan_involvement": "Leptin glycosylation modulates receptor binding and signaling.", "mechanism": "Leptin from adipose tissue increases aromatase activity, promoting E2 synthesis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12210177" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated fatty liver disease (MASLD)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects enzyme activity.", "mechanism": "Elevated GGT reflects liver dysfunction and oxidative stress in MASLD.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12210177" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated fatty liver disease (MASLD)", "glycan_involvement": "E2 transport and clearance are modulated by glycoproteins (SHBG, hepatic enzymes).", "mechanism": "Elevated E2 is associated with increased severity of MASLD and metabolic disturbances.", "protein": "Estradiol (E2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12210177" }, { "confidence": "high", "disease": "Gynecomastia (GYN)", "glycan_involvement": "T bioavailability is regulated by glycoprotein SHBG.", "mechanism": "Low T levels reduce inhibition of breast tissue proliferation, increasing GYN risk.", "protein": "Testosterone (T)", "protein_enriched": { "function": "Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine", "gene_name": "TFF1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P04155" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12210177" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Insulin is a glycoprotein precursor; glycosylation affects its stability and secretion.", "mechanism": "High insulin levels (hyperinsulinemia) are a risk factor for development of MASLD via promotion of hepatic steatosis and metabolic dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation of insulin precursor may affect bioactivity; not directly discussed.", "mechanism": "Elevated insulin increases risk of progression to cirrhosis, especially with high alcohol intake.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "Elevated liver function tests (LFT)", "glycan_involvement": "Indirect; insulin glycosylation may affect clearance.", "mechanism": "High insulin predicts future pathological LFTs (ALT, AST, AP, GGT), indicating liver injury.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect serum stability.", "mechanism": "ALT elevation is a marker of hepatocellular injury in MASLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated; glycan status may influence detection.", "mechanism": "AST elevation reflects liver injury in MASLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "AP is highly glycosylated; glycan structure affects activity and half-life.", "mechanism": "AP elevation is associated with cholestatic and metabolic liver disease.", "protein": "AP", "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "GGT is glycosylated; glycosylation modulates enzyme activity.", "mechanism": "GGT elevation is a sensitive marker of liver dysfunction in MASLD.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "Insulin glycosylation may affect hepatic metabolism.", "mechanism": "High insulin and alcohol intake synergistically increase risk of liver disease.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation of insulin precursor affects secretion and function.", "mechanism": "Insulin resistance and hyperinsulinemia precede and predict type 2 diabetes, which is linked to liver disease.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12210178" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis affects albumin function.", "mechanism": "Serum albumin (a glycoprotein) decreases in cirrhosis, reflecting synthetic dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210178" }, { "confidence": "high", "disease": "Febrile neutropenia", "glycan_involvement": "G-CSF is a glycoprotein; glycosylation affects its stability and bioactivity.", "mechanism": "G-CSF is administered to stimulate neutrophil production and reduce risk/severity of febrile neutropenia during chemotherapy.", "protein": "Granulocyte colony-stimulating factor (G-CSF)", "protein_enriched": { "function": "Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood,", "gene_name": "CSF3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P09919" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12212937" }, { "confidence": "high", "disease": "Castration-resistant prostate cancer (CRPC)", "glycan_involvement": "PSA is a glycoprotein; glycosylation patterns may affect its detection and disease specificity.", "mechanism": "PSA levels are used to monitor prostate cancer progression and response to therapy.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12212937" }, { "confidence": "high", "disease": "Allergic bronchopulmonary aspergillosis (ABPA)", "glycan_involvement": "CEA is heavily N-glycosylated; glycosylation affects its secretion and stability.", "mechanism": "Elevated serum CEA in ABPA is likely due to increased production by inflamed airway epithelial cells and/or decreased clearance due to mucus plugs.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Allergic bronchopulmonary aspergillosis (ABPA)", "glycan_involvement": "SCC antigen is glycosylated; glycosylation modulates its secretion.", "mechanism": "Elevated SCC antigen in ABPA may result from increased production by bronchial epithelial cells during chronic inflammation and impaired clearance.", "protein": "Squamous cell carcinoma antigen (SCC antigen)", "protein_enriched": { "function": "May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of", "gene_name": "SERPINB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Allergic bronchopulmonary aspergillosis (ABPA)", "glycan_involvement": "SLX is a sialylated glycan epitope on glycoproteins; its expression is upregulated in inflammation.", "mechanism": "Elevated SLX in ABPA is likely due to increased expression on airway epithelial glycoproteins during inflammation and mucus plugging.", "protein": "Sialyl Lewis X (SLX)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "N-glycosylation affects CEA secretion.", "mechanism": "CEA can be elevated in asthma due to chronic airway inflammation.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates SCC antigen levels.", "mechanism": "SCC antigen may be elevated in asthma due to epithelial cell activation.", "protein": "Squamous cell carcinoma antigen (SCC antigen)", "protein_enriched": { "function": "May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of", "gene_name": "SERPINB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Diffuse panbronchiolitis", "glycan_involvement": "SLX is a glycan modification upregulated in inflammation.", "mechanism": "SLX is elevated in diffuse panbronchiolitis due to increased glycan expression on airway glycoproteins.", "protein": "Sialyl Lewis X (SLX)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Altered glycosylation in cancer increases CEA secretion.", "mechanism": "CEA is a classical tumour marker for lung cancer, produced by malignant epithelial cells.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Cancer-associated glycosylation changes increase SCC antigen levels.", "mechanism": "SCC antigen is a tumour marker for squamous cell carcinoma of the lung.", "protein": "Squamous cell carcinoma antigen (SCC antigen)", "protein_enriched": { "function": "May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of", "gene_name": "SERPINB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "SLX is a cancer-associated glycan modification.", "mechanism": "SLX is elevated in lung cancer due to increased glycan expression on tumour cell glycoproteins.", "protein": "Sialyl Lewis X (SLX)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "medium", "disease": "Allergic bronchopulmonary aspergillosis (ABPA)", "glycan_involvement": "N-glycosylation is essential for CEA secretion.", "mechanism": "Eosinophils may contribute to CEA secretion in ABPA, but epithelial cell production is likely dominant.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213056" }, { "confidence": "high", "disease": "Cancer (multidrug resistance)", "glycan_involvement": "N-glycosylation is required for proper folding, trafficking, and function of P-gp.", "mechanism": "P-gp extrudes chemotherapeutic drugs, leading to drug resistance in cancer cells.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12213397" }, { "confidence": "high", "disease": "Immune cell dysfunction (T cell subsets, iNKT cells)", "glycan_involvement": "N-glycosylation supports surface expression and efflux activity of P-gp.", "mechanism": "High P-gp expression in iNKT and memory T cells alters mitochondrial dye retention, confounding metabolic measurements.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12213397" }, { "confidence": "medium", "disease": "Cancer (multidrug resistance)", "glycan_involvement": "Glycosylation state may affect inhibitor binding and P-gp stability.", "mechanism": "P-gp inhibitors (e.g., PSC833) can restore drug sensitivity in resistant cancer cells.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213397" }, { "confidence": "medium", "disease": "Immune cell dysfunction (T cell subsets, iNKT cells)", "glycan_involvement": "N-glycosylation ensures functional efflux capacity.", "mechanism": "High P-gp activity may protect innate-like T cells from chemotoxicity in tumor environments.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12213397" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation maintains MOG's native conformation, critical for antibody recognition.", "mechanism": "MOG acts as a CNS autoantigen; anti-MOG IgG triggers immune-mediated demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "MOG antibody-associated cerebral cortical encephalitis (MOG-CCE)", "glycan_involvement": "Native glycosylation of MOG is essential for pathogenic antibody binding.", "mechanism": "Anti-MOG IgG mediates cortical inflammation and seizures via immune attack on myelin.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation-dependent epitope recognition by autoantibodies.", "mechanism": "Anti-MOG antibodies induce demyelination of optic nerve.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "Transverse myelitis", "glycan_involvement": "Glycosylation affects antigenicity and immune response.", "mechanism": "Anti-MOG IgG triggers immune-mediated spinal cord demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation preserves antigenic structure for antibody binding.", "mechanism": "Anti-MOG antibodies mediate widespread CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "Relapsing MOGAD", "glycan_involvement": "Glycosylation-dependent antibody detection in live cell-based assays.", "mechanism": "High-titer anti-MOG IgG predicts relapse risk and guides immunotherapy.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213655" }, { "confidence": "medium", "disease": "Relapsing MOGAD", "glycan_involvement": "Not specified in article.", "mechanism": "Reduced TNFAIP3 levels correlate with relapse episodes.", "protein": "TNF-alpha-induced protein 3 (TNFAIP3)", "relationship_type": "biomarker", "source_pmcid": "PMC12213655" }, { "confidence": "medium", "disease": "Brainstem encephalitis", "glycan_involvement": "Glycosylation-dependent antigenicity.", "mechanism": "Anti-MOG IgG mediates demyelination in brainstem regions.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation maintains antigenic epitopes.", "mechanism": "Anti-MOG IgG associated with meningeal inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "medium", "disease": "Demyelinating pseudotumor", "glycan_involvement": "Glycosylation-dependent antibody binding.", "mechanism": "Anti-MOG IgG triggers focal demyelinating lesions mimicking tumors.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12213655" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "PCSK9 is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "PCSK9 promotes LDL receptor degradation, raising LDL-C and ASCVD risk; inhibition lowers LDL-C and events.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "Familial hypercholesterolemia", "glycan_involvement": "Glycosylation may modulate PCSK9 stability and receptor interaction.", "mechanism": "Gain-of-function mutations in PCSK9 cause elevated LDL-C and familial hypercholesterolemia.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "LDL receptor clears LDL-C; upregulation reduces ASCVD risk.", "protein": "LDL receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "Familial hypercholesterolemia", "glycan_involvement": "Glycosylation affects LDL particle structure and receptor interaction.", "mechanism": "Mutations in ApoB-100 impair LDL receptor binding, causing familial hypercholesterolemia.", "protein": "Apolipoprotein B-100", "relationship_type": "causal", "source_pmcid": "PMC12214137" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "O-glycosylation modulates ApoC3 function and clearance.", "mechanism": "ApoC3 inhibits lipoprotein lipase; antisense oligonucleotides lower triglycerides and LDL-C.", "protein": "Apolipoprotein C3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Lp(a) contains heavily glycosylated apolipoprotein(a), affecting plasma levels and atherogenicity.", "mechanism": "Elevated Lp(a) is an independent ASCVD risk factor; antisense/siRNA therapies lower Lp(a).", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "medium", "disease": "Homozygous familial hypercholesterolemia (HoFH)", "glycan_involvement": "ANGPTL3 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "ANGPTL3 inhibition lowers LDL-C independent of LDL receptor function.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation influences HDL structure and function.", "mechanism": "ApoA1 is main HDL protein; enhancing ApoA1/HDL function may reduce ASCVD risk.", "protein": "Apolipoprotein A1", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "Glycosylation modulates PCSK9 secretion and function.", "mechanism": "PCSK9 increases LDL-C by degrading LDL receptor; inhibition lowers cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12214137" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation affects ApoB-100 secretion and lipoprotein assembly.", "mechanism": "ApoB-100 levels reflect VLDL/LDL secretion, linked to hepatic steatosis and NASH risk.", "protein": "Apolipoprotein B-100", "relationship_type": "biomarker", "source_pmcid": "PMC12214137" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "APP is N-glycosylated, affecting trafficking and processing.", "mechanism": "Triplication of APP gene leads to A\u03b2 overproduction and plaque formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "MFGE8 is glycosylated, which may affect its secretion and aggregation properties.", "mechanism": "Decreased MFGE8 in CSF; its cleavage product (medin) aggregates with A\u03b2, promoting CAA.", "protein": "MFGE8", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "SPON1 is heavily glycosylated, modulating ECM interactions.", "mechanism": "Elevated in DSAD CSF and plaques; associated with ECM remodeling and plaque formation.", "protein": "SPON1", "protein_enriched": { "function": "Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro. May contribute to the growth and guidance of axons in both the spinal", "gene_name": "SPON1", "glycan_count": 26, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G27058EU", "G28541PG", "G37399XV", "G39446WN", "G41247ZX", "G59626AS", "G59924QI", "G62765YT", "G65184UU", "G72291OX", "G72398FA", "G80920RR", "G82463GQ", "G90659AW", "G95865ZB", "G61491DK" ], "uniprot_id": "Q9HCB6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "Collagens are glycosylated, influencing ECM stability and vascular integrity.", "mechanism": "Elevated in DSAD CSF and brain; associated with vascular changes in CAA.", "protein": "COL6A1", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "White matter pathology", "glycan_involvement": "MAG is N-glycosylated, essential for myelin-axon interactions.", "mechanism": "Decreased in DSAD CSF and brain; marker of myelin integrity.", "protein": "MAG", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "White matter pathology", "glycan_involvement": "MOG is N-glycosylated, affecting immune recognition and myelin stability.", "mechanism": "Decreased in DSAD CSF and brain; marker of myelin integrity.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "CHI3L1 is glycosylated, modulating its stability and immune function.", "mechanism": "Elevated in DSAD CSF prior to cognitive decline; marker of astrocytosis and inflammation.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "IgG/IgA are N-glycosylated, affecting effector functions and BBB crossing.", "mechanism": "Elevated in DSAD CSF; may reflect BBB dysfunction and immune activation.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "Complement proteins are glycosylated, influencing activation and clearance.", "mechanism": "Elevated in DSAD CSF; involved in synaptic pruning and neuroinflammation.", "protein": "Complement proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "DSAD", "glycan_involvement": "NPTX2 is glycosylated, affecting secretion and synaptic localization.", "mechanism": "Decreased early in DSAD CSF; marker of synaptic dysfunction.", "protein": "NPTX2", "protein_enriched": { "function": "May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses", "gene_name": "NPTX1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q15818" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214755" }, { "confidence": "high", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Elevated fucosylation and reduced N-acetylneuraminic acid (sialylation) on IgG N-glycans.", "mechanism": "Distinct IgG N-glycosylation patterns (increased fucosylation, decreased sialylation) differentiate ASS patients from healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Glycosylation changes affect Fc receptor binding and immune effector functions.", "mechanism": "Altered IgG glycosylation (increased fucosylation, decreased sialylation) may contribute to immune dysregulation and disease pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12214897" }, { "confidence": "high", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Site-specific N-glycosylation patterns linked to clinical features.", "mechanism": "Specific IgG N-glycopeptides correlate with clinical manifestations (rash, muscle weakness, Raynaud\u2019s, arthralgia) and disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Altered N-glycosylation associated with pulmonary involvement.", "mechanism": "IgG glycosylation patterns (intact N-glycopeptides) correlate with lung function parameters in ASS patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Elevated fucosylation on IgG N-glycans.", "mechanism": "Increased IgG fucosylation is positively correlated with SLE disease activity index (SLEDAI).", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "N-glycan composition changes on IgG.", "mechanism": "Altered IgG glycosylation (decreased galactosylation, increased fucosylation) associated with disease activity and synovitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Idiopathic inflammatory myopathy (IIM)", "glycan_involvement": "Subclass-specific N-glycosylation differences.", "mechanism": "IgG glycosylation changes (especially in anti-Jo-1 positive patients) distinguish IIM subtypes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "low", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Afucosylated IgG enhances ADCC; fucosylation reduces it.", "mechanism": "Glycosylation modifications (e.g., afucosylation) may be exploited to modulate IgG effector functions for therapy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214897" }, { "confidence": "medium", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Reduced sialylation in ASS may diminish protective effects.", "mechanism": "Sialylated IgG exerts anti-inflammatory effects via CD23/CD22 interactions, potentially counteracting disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12214897" }, { "confidence": "low", "disease": "Anti-synthetase syndrome (ASS)", "glycan_involvement": "Decreased N-glycosylation on IgG2.", "mechanism": "Reduced glycosylation of IgG2 subclass may reflect subclass switching or immune compensation in ASS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12214897" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation of MOG affects antigenicity and immune recognition.", "mechanism": "MOG is the autoantigen used to induce EAE, mimicking MS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD19 is a glycoprotein; glycosylation may affect B cell activation/migration.", "mechanism": "Increased CNS-infiltrating CD19+ B cells, especially TNF-producing, correlate with MS/EAE severity.", "protein": "CD19 (B cell marker)", "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD4 glycosylation modulates T cell receptor signaling and trafficking.", "mechanism": "CD4+ T cells produce proinflammatory cytokines (TNF, IFN-\u03b3, IL-17) driving neuroinflammation.", "protein": "CD4 (T cell marker)", "protein_enriched": { "function": "Transcriptional corepressor that mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription (PubM", "gene_name": "Ncor2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G85282JO" ], "uniprot_id": "Q9WU42" }, "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD8 glycosylation influences cytotoxic function and migration.", "mechanism": "CD8+ T cells infiltrate CNS, produce TNF/IFN-\u03b3/IL-17, and correlate with disease progression.", "protein": "CD8 (T cell marker)", "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "iNOS is glycosylated; glycosylation may affect stability/activity.", "mechanism": "iNOS+ macrophages (M1) are increased in severe EAE/MS lesions, indicating inflammation.", "protein": "Inducible nitric oxide synthase (iNOS)", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7503239). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosy", "gene_name": "Nos2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29477" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214946" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Arg1 glycosylation may regulate enzyme activity.", "mechanism": "Arg1+ macrophages (M2) are associated with anti-inflammatory response and tissue repair.", "protein": "Arginase 1 (Arg1)", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592)", "gene_name": "Rpl13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47963" }, "relationship_type": "protective", "source_pmcid": "PMC12214946" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "FoxP3 is glycosylated; glycosylation may affect nuclear localization/function.", "mechanism": "FoxP3+ Treg cells suppress neuroinflammation; higher in milder EAE (6N substrain).", "protein": "FoxP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:22813742). Plays an essential role in maintaining homeostasis of the immune ", "gene_name": "Foxp3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99JB6" }, "relationship_type": "protective", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IL-10 glycosylation affects secretion and receptor binding.", "mechanism": "IL-10-producing cells (T/B cells) correlate with improved disease state and reduced inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "TNF glycosylation modulates receptor interaction and bioactivity.", "mechanism": "TNF produced by T/B cells and macrophages drives neuroinflammation and demyelination.", "protein": "Tumor necrosis factor (TNF)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "Tnf", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P06804" }, "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IFN-\u03b3 glycosylation influences stability and immune signaling.", "mechanism": "IFN-\u03b3 produced by T cells promotes Th1 response and CNS inflammation.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "causal", "source_pmcid": "PMC12214946" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Altered N-glycosylation at specific site correlates with disease state.", "mechanism": "Upregulated N-glycosylation at NPTX1_154 in PD and aged hippocampus; involved in axonogenesis and synaptic function.", "protein": "NPTX1", "protein_enriched": { "function": "Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (By similarity). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibi", "gene_name": "Macroh2a1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9QZQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "N-glycosylation changes at site 84.", "mechanism": "Co-regulated glycosylation changes in PD and aging; involved in lysosomal function.", "protein": "MPRD", "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Altered N-glycosylation at site 824.", "mechanism": "Hub glycosite in module associated with PD and aging; impacts synaptic transmission.", "protein": "CA2D1", "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation at site 94 is reduced.", "mechanism": "Downregulated N-glycosylation in AD and aging; involved in nervous system development and cell adhesion.", "protein": "THY1", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "Thy1", "glycan_count": 43, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06110VR", "G23294PN", "G25418HZ", "G33609NS", "G45504EY", "G46902YN", "G50045TK", "G63628AV", "G65092SV", "G66538GV", "G80223IX", "G82119TF", "G84820NF", "G00406II", "G02815KT", "G05724UK", "G06356OH", "G10773YW", "G14669DU", "G24835MQ", "G25637MV", "G29880MM", "G31916IQ", "G39188ZX", "G44215PV", "G46687AB", "G49874UX", "G54612UD", "G64527OM", "G70101JE", "G70418MS", "G70961NC", "G72735IY", "G74430RZ", "G76613WN", "G85228QD", "G93180LE", "G94854LT", "G49108TO", "G10256JP", "G23863VK", "G79666IR", "G82830MN" ], "uniprot_id": "P01831" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation at site 270 is reduced.", "mechanism": "Downregulated N-glycosylation in AD and aging; impacts cell adhesion and neural development.", "protein": "NRCAM", "protein_enriched": { "function": "Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribos", "gene_name": "Eif3i", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9QZD9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation at site 283 is increased.", "mechanism": "Upregulated N-glycosylation in AD substantia nigra; involved in lysosomal function.", "protein": "NPTN", "protein_enriched": { "function": "Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (By similarity). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibi", "gene_name": "Macroh2a1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QZQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "medium", "disease": "Liver/Lung Disease (general metabolic dysfunction)", "glycan_involvement": "N-glycosylation regulates Hexa activity and metabolic pathways.", "mechanism": "Master regulator of glycan synthesis/degradation; highly connected in liver/lung glycoprotein networks.", "protein": "Hexa", "relationship_type": "causal", "source_pmcid": "PMC12215503" }, { "confidence": "medium", "disease": "Lung Adenocarcinoma", "glycan_involvement": "N-glycosylation at multiple sites (N417 in brain, 7 sites in heart/lung) modulates activity.", "mechanism": "Promotes fatty acid uptake and tumor progression; tissue-specific glycosylation impacts function.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12215503" }, { "confidence": "medium", "disease": "Brain Aging", "glycan_involvement": "N-glycosylation regulates neural ion transport.", "mechanism": "Highly glycosylated in brain; abundance decreases with aging.", "protein": "AT1B2", "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "medium", "disease": "Brain Aging", "glycan_involvement": "N-glycosylation modulates synaptic signaling.", "mechanism": "Brain-enriched glycoprotein; glycosylation declines with age.", "protein": "EAA2", "relationship_type": "biomarker", "source_pmcid": "PMC12215503" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "EGFR is a glycoprotein; glycosylation affects receptor function and drug sensitivity.", "mechanism": "EGFR mutations drive NSCLC progression; TKIs inhibit EGFR signaling, improving survival.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Adenocarcinoma", "glycan_involvement": "EGFR glycosylation modulates ligand binding and downstream signaling.", "mechanism": "EGFR mutations are prevalent in lung adenocarcinoma and predict TKI response.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12215561" }, { "confidence": "medium", "disease": "Squamous cell carcinoma", "glycan_involvement": "Glycosylation status may affect EGFR detection and function.", "mechanism": "EGFR mutations are rare but present in squamous cell carcinoma; may guide therapy.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12215561" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "No direct glycan involvement described for ILD risk.", "mechanism": "EGFR-TKI therapy can induce ILD as an adverse event.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Mutations may alter glycosylation patterns, affecting drug binding.", "mechanism": "EGFR exon 19 deletion and L858R mutation predict sensitivity to TKIs.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12215561" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Potential impact on glycosylation and receptor conformation.", "mechanism": "Uncommon EGFR mutations (S768I, G719X, L861Q) respond to 2nd/3rd gen TKIs.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Mutation may affect glycosylation and drug accessibility.", "mechanism": "T790M mutation confers resistance to 1st/2nd gen TKIs; Osimertinib overcomes resistance.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may influence mutation detection and receptor activity.", "mechanism": "EGFR mutation status guides selection of TKI therapy.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation affects EGFR structure and drug binding.", "mechanism": "EGFR glycoprotein targeted by TKIs (Erlotinib, Gefitinib, Afatinib, Osimertinib) for NSCLC treatment.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation impacts EGFR stability and cell surface expression.", "mechanism": "EGFR expression and mutation status used for diagnosis and prognosis.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12215561" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation is critical for ACE2 binding, viral fusion, and immune evasion.", "mechanism": "Spike mediates viral entry via ACE2 binding and membrane fusion.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12217048" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Lectin binding depends on Spike glycan motifs (high mannose, complex, fucosylated).", "mechanism": "Lectins binding to Spike glycans may block virus attachment or entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Specific lectin binding patterns reflect Spike glycan composition.", "mechanism": "Lectin array profiling of Spike glycosylation can distinguish viral presence.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12217048" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Target high mannose/hybrid N-glycans on Spike.", "mechanism": "Mannose-binding lectins (AMA, BANLEC, GNA, NPA) can bind Spike and virions, suggesting antiviral potential.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binds complex-type N-glycans at RBD (N331, N343).", "mechanism": "Complex N-glycan-binding lectin (RCA-120) may inhibit ACE2 binding by targeting RBD glycans.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Target \u03b11-6 core fucosylated N-glycans.", "mechanism": "Fucose-binding lectins (AAL, PA-IIL, RS-FUC) bind core-fucosylated Spike glycans, potentially blocking entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Differences in N-glycan extensions and O-glycan cores.", "mechanism": "Lectin binding profiles can differentiate recombinant Spike from intact virions, reflecting cell-type specific glycosylation.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Complex glycans with Lewis structures on Spike.", "mechanism": "Lectins binding Lewis antigens (e.g., Lewis A/B/X/Y, Blood group H) may target unique Spike glycan extensions.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Recognize high mannose and hybrid N-glycans.", "mechanism": "Lectins (GRFT, Lentil, HHA, Gal3) previously shown to have anti-SARS-CoV-2 activity bind Spike glycans.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12217048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike glycan motifs provide unique lectin binding signatures.", "mechanism": "Lectin array can be used for diagnostic detection of SARS-CoV-2 via glycan profiling.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12217048" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein affects its antigenicity and immune recognition.", "mechanism": "Linear epitopes from the N-terminal domain (NTD) of S protein are recognized by antibodies in patient sera, enabling serological diagnosis.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates S protein structure and immune evasion.", "mechanism": "S protein is a primary target for vaccine design and antiviral therapy due to its role in viral entry and immune response stimulation.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for proper folding and function of S protein.", "mechanism": "S protein mediates viral entry by facilitating fusion of viral and host cell membranes.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "causal", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation sites in NTD influence antibody accessibility.", "mechanism": "NTD-specific neutralizing antibodies are produced in response to infection, serving as markers of exposure.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Native glycosylation may affect epitope presentation; recombinant protein may lack native glycosylation.", "mechanism": "Recombinant NTD linear epitopes enable ELISA-based detection of COVID-19-specific antibodies with high sensitivity and specificity.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation can shield epitopes from immune recognition.", "mechanism": "Antibodies against S protein, especially NTD and RBD, contribute to immune protection.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "protective", "source_pmcid": "PMC12218876" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status may affect test accuracy.", "mechanism": "Serological tests targeting S protein epitopes improve early detection and disease management.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences immunogenicity and antibody response.", "mechanism": "Presence of IgG/IgM antibodies against S protein indicates infection and immune status.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect epitope stability and recognition.", "mechanism": "NTD linear epitopes are promising candidates for point-of-care diagnostic tests.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns influence vaccine efficacy.", "mechanism": "S protein is targeted by neutralizing antibodies elicited by vaccines.", "protein": "SARS-CoV-2 Spike Glycoprotein (S)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12218876" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "N-glycosylation modulates stability and clearance.", "mechanism": "Scavenges free heme, reducing iron-mediated injury and infarct size.", "protein": "Hemopexin", "protein_enriched": { "function": "Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation", "gene_name": "HPX", "glycan_count": 236, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00875VP", "G00912UN", "G01650EU", "G02528FI", "G02886BB", "G04657PL", "G04854VP", "G05933EN", "G06247RL", "G06356OH", "G06853GH", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G14572XX", "G14994KB", "G15169WU", "G18647XP", "G20425TQ", "G22140GZ", "G22276PO", "G22310AV", "G22572EH", "G23294PN", "G23863VK", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G30769VJ", "G31118FR", "G31916IQ", "G36131WL", "G37818NZ", "G37868ZX", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G42358LZ", "G43223CG", "G44576HQ", "G45395BF", "G45504EY", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G47702MW", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55412XP", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G62165AG", "G63980BQ", "G64394MX", "G65019XG", "G66163OV", "G66621EA", "G68735SN", "G70232NH", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G72797UR", "G74772YG", "G75983OB", "G76417NN", "G78644BR", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82463GQ", "G82830MN", "G83555HU", "G84452RH", "G85144OK", "G86056PA", "G86182NS", "G86234IN", "G86752LQ", "G86795LJ", "G86880BF", "G87399DK", "G88374WZ", "G89205CJ", "G90093AU", "G90659AW", "G92135MA", "G92275SC", "G92406TI", "G94470IW", "G94917XT", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G00273SJ", "G14669DU", "G22768VO", "G60861FA", "G77669RF", "G89045VA", "G92551JA", "G57321FI", "G42962KI", "G44215PV", "G46687AB", "G60923RB", "G71146HJ", "G17015OC", "G29931IJ", "G43417UB", "G74722FL", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G01485JJ", "G02030ZB", "G10819WX", "G12745LE", "G14547CB", "G14972EH", "G15127JD", "G20528HD", "G20706XG", "G25418HZ", "G26915XM", "G27915IV", "G30248BL", "G30970QQ", "G31852PQ", "G31986NC", "G33416PL", "G35253PZ", "G37412TK", "G37509XX", "G37692EO", "G37995HC", "G39619TI", "G41071NU", "G43669FQ", "G43734MM", "G46524LG", "G54010QB", "G56284ZY", "G58087IP", "G58954YZ", "G60834IK", "G61256FT", "G62461SM", "G63381RX", "G67164EE", "G69521XL", "G71463BG", "G72398FA", "G72787SB", "G75798PH", "G76329HL", "G77547TA", "G78502KD", "G81124ET", "G81295CK", "G85269DF", "G85554PZ", "G85677PP", "G87389XI", "G89098OM", "G92081HT", "G98129XB", "G01160VV", "G05049YU", "G05724UK", "G05962QB", "G07246CJ", "G07755XJ", "G11911BT", "G12341GU", "G12579WK", "G15038BD", "G15664MX", "G17208MA", "G23505EP", "G30740WO", "G34989PA", "G35029YA", "G39188ZX", "G40206WX", "G41247ZX", "G44753VC", "G47950XN", "G49018RC", "G49642SA", "G49906RN", "G49955PK", "G56307ZW", "G59324HL", "G62765YT", "G64275UO", "G64527OM", "G68490OW", "G70101JE", "G70441OD", "G72790NZ", "G75418YA", "G76295SF", "G80920RR", "G83646BJ", "G84225JN", "G85282JO", "G87661QW", "G90734RJ", "G95977AE", "G96430BV" ], "uniprot_id": "P02790" }, "relationship_type": "protective", "source_pmcid": "PMC12219343" }, { "confidence": "high", "disease": "STEMI", "glycan_involvement": "N-glycosylation affects hemoglobin binding and immune recognition.", "mechanism": "Binds cell-free hemoglobin, limiting oxidative damage.", "protein": "Haptoglobin-related protein", "protein_enriched": { "function": "Primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL). This HDL particle, termed trypanosome lytic factor-1 (TLF-1), mediates human inna", "gene_name": "HPR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00739" }, "relationship_type": "protective", "source_pmcid": "PMC12219343" }, { "confidence": "high", "disease": "Acute phase response", "glycan_involvement": "Highly glycosylated; glycan changes modulate anti-inflammatory properties.", "mechanism": "Immunomodulation during inflammation; upregulated in SGLT2i users.", "protein": "Alpha-1-acid glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "N-glycosylation required for function and anti-calcification activity.", "mechanism": "Inhibits vascular and valvular calcification, improving outcomes.", "protein": "Alpha-2-HS-glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "Acute phase response", "glycan_involvement": "N-glycosylation influences anti-inflammatory activity.", "mechanism": "Anti-inflammatory response; upregulated in SGLT2i users.", "protein": "Inter-alpha-trypsin inhibitor heavy chain H4", "protein_enriched": { "function": "Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration", "gene_name": "ITIH4", "glycan_count": 191, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00912UN", "G03081ER", "G03382KH", "G08146BT", "G10486CT", "G22310AV", "G23863VK", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G48414YA", "G49874UX", "G56069TX", "G56903ZB", "G57818FI", "G59411JK", "G61937QU", "G68800OF", "G70418MS", "G72667IM", "G78261DB", "G84452RH", "G91636VS", "G95977AE", "G05724UK", "G06110VR", "G39188ZX", "G55220VL", "G64527OM", "G66676MI", "G80966KZ", "G82020ZR", "G02030ZB", "G03644CB", "G04854VP", "G05642HQ", "G05933EN", "G06192YD", "G06247RL", "G06356OH", "G08918WF", "G10256JP", "G10819WX", "G10846ZT", "G11629QQ", "G11911BT", "G12341GU", "G12793SR", "G13165FV", "G14547CB", "G14994KB", "G15169WU", "G15664MX", "G15828HX", "G16758MX", "G20076CD", "G24303GI", "G24954UD", "G26330YA", "G27058EU", "G27102CT", "G27126ED", "G27947YN", "G28681TP", "G31153XO", "G31916IQ", "G31986NC", "G32246SI", "G34617SM", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G47518TP", "G47737VJ", "G49018RC", "G51941GC", "G52527GH", "G54010QB", "G55412XP", "G56518TU", "G57776ZS", "G58087IP", "G59324HL", "G59536GA", "G59626AS", "G60070LT", "G60834IK", "G62765YT", "G63980BQ", "G64394MX", "G65186XA", "G65344XH", "G68209WQ", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72747WU", "G72797UR", "G75418YA", "G75983OB", "G77669RF", "G79939YZ", "G80075MS", "G81263BG", "G82830MN", "G83204BU", "G83213GG", "G83295QG", "G83633GK", "G85144OK", "G85269DF", "G85554PZ", "G86795LJ", "G86880BF", "G88325OQ", "G88374WZ", "G90093AU", "G90386IR", "G90659AW", "G91473PK", "G92081HT", "G93656SY", "G93860XO", "G94470IW", "G94917XT", "G95865ZB", "G99668VU", "G99950SF", "G31665QC", "G39595FH", "G44211QA", "G55216FT", "G60033FS", "G78166NF", "G87015RU", "G90789YQ", "G97876DH", "G17015OC", "G27391WQ", "G29068FM", "G43417UB", "G58001LT", "G57317CE", "G35029YA", "G53434XO", "G88713AC", "G74722FL", "G74724QE", "G27945LI", "G81006GJ", "G00273SJ", "G01650EU", "G14260UH", "G14972EH", "G20425TQ", "G22140GZ", "G22572EH", "G23294PN", "G23432EQ", "G36131WL", "G37412TK", "G39943KJ", "G43223CG", "G47748JZ", "G49906RN", "G50045TK", "G56238AO", "G58954YZ", "G60967DT", "G68490OW", "G69521XL", "G75798PH", "G78649WQ", "G78787DI", "G78790NZ", "G79568CQ", "G81295CK", "G84225JN", "G84820NF", "G86182NS", "G94120DZ" ], "uniprot_id": "Q14624" }, "relationship_type": "biomarker", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "Apoptosis", "glycan_involvement": "Glycosylation affects binding to apoptotic cells.", "mechanism": "Promotes clearance of apoptotic cells during acute phase response.", "protein": "Serum amyloid P-component", "relationship_type": "biomarker", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "N-glycosylation critical for anticoagulant function.", "mechanism": "Modulates coagulation and inflammation; upregulated in SGLT2i users.", "protein": "Beta-2-glycoprotein 1", "relationship_type": "protective", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "N-glycosylation modulates stability and activity.", "mechanism": "Associated with heme scavenging and metabolic regulation.", "protein": "Zinc-alpha-2-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12219343" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "N-glycosylation affects immune function and heme binding.", "mechanism": "Binds free heme when traditional scavengers are overwhelmed.", "protein": "Immunoglobulin heavy constant alpha 1", "relationship_type": "protective", "source_pmcid": "PMC12219343" }, { "confidence": "low", "disease": "Heart failure post-infarction", "glycan_involvement": "N-glycosylation influences stability and transport.", "mechanism": "Upregulated in SGLT2i users; may reflect improved cardiac function.", "protein": "Transthyretin", "relationship_type": "biomarker", "source_pmcid": "PMC12219343" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "PSA is glycosylated; glycoforms may affect detection and specificity.", "mechanism": "Elevated serum PSA indicates prostate epithelial cell activity; used for diagnosis and monitoring.", "protein": "Prostate Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Benign Prostatic Hyperplasia (BPH)", "glycan_involvement": "Altered glycosylation may distinguish BPH from cancer PSA.", "mechanism": "PSA levels can be elevated in BPH, reducing specificity for cancer.", "protein": "Prostate Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "hK2 is glycosylated; glycoforms may influence activity and detection.", "mechanism": "hK2 levels are integrated in the 4Kscore to predict aggressive PCa.", "protein": "Human Kallikrein-2 (hK2)", "protein_enriched": { "function": "Receptor for ecdysone. May be an important modulator of insect metamorphosis. Plays an important part in embryonic and post-embryonic development. Binds to ecdysone response elements (ECRES) such as i", "gene_name": "usp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20153" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation may affect membrane localization and function.", "mechanism": "Overexpression linked to androgen resistance and progression; inhibits apoptosis.", "protein": "Bcl-2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation may affect nuclear localization and stability.", "mechanism": "High Ki-67 expression correlates with increased proliferation, poor prognosis, and recurrence.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Potential glycosylation may modulate nuclear function.", "mechanism": "Overexpression associated with aggressive and metastatic PCa; regulates cell cycle and chromatin.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221370" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Potential glycosylation may affect translation initiation.", "mechanism": "Gene amplification (8q gain) linked to high Gleason score and advanced disease.", "protein": "EIF3S (EIF3A)", "protein_enriched": { "function": "RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). ", "gene_name": "EIF3A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q14152" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 overexpression associated with poor prognosis; target for immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation affects secretion and detection.", "mechanism": "KLK3 mRNA used in SelectMDx for risk stratification of high-grade PCa.", "protein": "KLK3 (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221370" }, { "confidence": "medium", "disease": "Docetaxel-resistant Prostate Cancer", "glycan_involvement": "Potential glycosylation may affect protein stability.", "mechanism": "Upregulated via exosomal circ-XIAP; associated with chemoresistance and apoptosis evasion.", "protein": "TPD52", "protein_enriched": { "function": "", "gene_name": "TPD52L1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16890" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221370" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "CD47 is a heavily glycosylated protein; glycosylation is essential for its 'don't eat me' signal.", "mechanism": "CD47 on nanoparticle surface enables immune evasion by inhibiting macrophage uptake.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "protective", "source_pmcid": "PMC12221644" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "PD1 glycosylation affects its stability and receptor binding.", "mechanism": "PD1 on nanoparticle surface binds PDL1 on cancer cells, disrupting immune inhibitory axis and enhancing anti-tumor immunity.", "protein": "PD1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "PDL1 glycosylation regulates its expression and immune evasion.", "mechanism": "PDL1 on cancer cells interacts with PD1-modified nanoparticles, facilitating targeted delivery and immune modulation.", "protein": "PDL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "STAT3 is O-glycosylated, which can affect its transcriptional activity.", "mechanism": "STAT3 silencing via siRNA-loaded nanoparticles inhibits tumor growth and stimulates anti-tumor immune response.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Bcl2 glycosylation modulates its anti-apoptotic function.", "mechanism": "Bcl2 silencing via siRNA-loaded, macrophage membrane-coated nanoparticles induces apoptosis and inhibits tumor growth.", "protein": "Bcl2", "protein_enriched": { "function": "Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondria", "gene_name": "BCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10415" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "EGFR N-glycosylation is critical for ligand binding and receptor activation.", "mechanism": "EGFR silencing via ER membrane-coated nanoparticles bypasses lysosomal degradation and suppresses tumor growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is extensively N-glycosylated, forming a glycan shield that affects immune recognition.", "mechanism": "Nanoparticles functionalized with 12p1 peptide bind gp120, neutralizing HIV and inhibiting infection.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "tat is O-glycosylated, influencing its nuclear localization and function.", "mechanism": "siRNA-loaded nanoparticles silence tat gene, reducing HIV replication.", "protein": "tat", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "rev glycosylation affects its RNA binding and export function.", "mechanism": "siRNA-loaded nanoparticles silence rev gene, inhibiting HIV replication.", "protein": "rev", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221644" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "CXCR4 N-glycosylation modulates HIV entry and receptor function.", "mechanism": "CXCR4 on lymphocyte membranes facilitates nanoparticle targeting to HIV-infected cells.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC12221644" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma", "glycan_involvement": "CEA is a glycoprotein; glycosylation is essential for its secretion and detection.", "mechanism": "CEA is highly expressed in plasma of patients and predicts prognosis and recurrence after surgery.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "high", "disease": "Bladder Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation enables CEA's stability and detection in plasma.", "mechanism": "CEA levels rise with bladder metastasis and decrease after tumor resection, indicating disease status.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation is required for CEA's function as a biomarker.", "mechanism": "CEA has diagnostic value in oral SCC.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "medium", "disease": "Lung Adenocarcinoma", "glycan_involvement": "Glycosylation is necessary for CEA's biomarker activity.", "mechanism": "CEA is used for diagnosis and monitoring in lung adenocarcinoma.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma", "glycan_involvement": "SCC-Ag is a glycoprotein; glycosylation affects its secretion and detection.", "mechanism": "SCC-Ag levels correlate with tumor size, TNM staging, recurrence, and therapeutic response.", "protein": "Squamous Cell Carcinoma Antigen (SCC-Ag)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "high", "disease": "Bladder Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation is essential for SCC-Ag's biomarker function.", "mechanism": "SCC-Ag levels rise with bladder metastasis and decrease after tumor resection, reflecting disease status.", "protein": "Squamous Cell Carcinoma Antigen (SCC-Ag)", "relationship_type": "biomarker", "source_pmcid": "PMC12221895" }, { "confidence": "high", "disease": "Coronary heart disease", "glycan_involvement": "C3 is a glycoprotein; glycosylation required for function and stability.", "mechanism": "High plasma C3 levels in heavy smokers strongly associated with CHD prevalence, independent of other risk factors.", "protein": "C3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12221900" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "C4 glycosylation affects activation and deposition.", "mechanism": "C4 deposition in atherosclerotic lesions; smoking increases C4d deposition on endothelial cells.", "protein": "C4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12221900" }, { "confidence": "high", "disease": "Emphysema", "glycan_involvement": "C1q glycosylation modulates immune recognition.", "mechanism": "Chronic cigarette smoke downregulates C1q in lung APCs, leading to loss of tolerance and emphysema.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12221900" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "C3 glycosylation essential for complement activation.", "mechanism": "Smoke-induced alternative pathway activation increases C3a/C3b, promoting AMD; inhibition mitigates damage.", "protein": "C3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12221900" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "CFH glycosylation modulates regulatory activity.", "mechanism": "CFH Y402H variant increases lung cancer risk in smokers; tumor cells evade complement cytotoxicity via CFH.", "protein": "Factor H (CFH)", "relationship_type": "causal/genetic risk", "source_pmcid": "PMC12221900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "MAC assembly involves glycoprotein subunits.", "mechanism": "C5b-9 detected in atherosclerotic lesions; smoking promotes MAC formation and vascular injury.", "protein": "C5b-9 (MAC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12221900" }, { "confidence": "medium", "disease": "Oral mucosal inflammation", "glycan_involvement": "C3 glycosylation required for activation and cleavage.", "mechanism": "Smokeless tobacco extracts deplete C3, activate complement, and initiate oral mucosal inflammation.", "protein": "C3", "relationship_type": "causal", "source_pmcid": "PMC12221900" }, { "confidence": "medium", "disease": "Nasal mucosal damage", "glycan_involvement": "C3 glycosylation required for complement function.", "mechanism": "C3-deficient mice protected from cigarette smoke-induced nasal injury; C3 activation mediates damage.", "protein": "C3", "relationship_type": "causal/protective", "source_pmcid": "PMC12221900" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "CD55 glycosylation affects cell surface expression and regulatory function.", "mechanism": "Upregulation of CD55 on endothelial cells exposed to smoke/shear stress limits excessive complement activation.", "protein": "CD55", "protein_enriched": { "function": "Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI)", "gene_name": "DDT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30046" }, "relationship_type": "protective", "source_pmcid": "PMC12221900" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "C3 glycosylation influences susceptibility to modification and activation.", "mechanism": "Cigarette smoke modifies C3, activates alternative pathway, increases neutrophil/monocyte chemotaxis in lungs.", "protein": "C3", "relationship_type": "causal", "source_pmcid": "PMC12221900" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation affects transporter stability and localization.", "mechanism": "Regulates renal uric acid reabsorption; dysfunction leads to elevated serum uric acid.", "protein": "Serum uric acid transporter (URAT1/SLC22A12)", "protein_enriched": { "function": "Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:12024214, PubMed:22194875, PubMed:", "gene_name": "SLC22A12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96S37" }, "relationship_type": "causal", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Fc glycosylation modulates immune activation.", "mechanism": "IgG coats MSU crystals, promoting phagocytosis and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation required for CRP secretion and function.", "mechanism": "CRP is elevated during acute gout flares and systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates SAA stability.", "mechanism": "SAA rises in response to gouty inflammation.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "N-glycosylation affects receptor-ligand binding.", "mechanism": "IL6R mediates inflammatory signaling in gouty arthritis.", "protein": "Interleukin-6 receptor (IL6R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "TNFRSF1A drives inflammatory cascades in gout.", "protein": "Tumor necrosis factor receptor (TNFRSF1A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation pattern changes in liver dysfunction.", "mechanism": "Altered transferrin glycosylation reflects liver injury in gout patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Highly glycosylated; glycan changes reflect inflammation.", "mechanism": "ORM1 increases during systemic inflammation in gout.", "protein": "Alpha-1-acid glycoprotein (ORM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation regulates fibronectin matrix assembly.", "mechanism": "Fibronectin deposition contributes to tissue fibrosis around gouty tophi.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12221985" }, { "confidence": "medium", "disease": "Migrating gout attack", "glycan_involvement": "N-glycosylation required for complement activation.", "mechanism": "Complement activation promotes systemic inflammatory response during acute gout migration.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221985" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for APS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12223463" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Autoantibodies against cardiolipin-binding glycoproteins are diagnostic for APS.", "protein": "Cardiolipin-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12223463" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation influences antibody effector function.", "mechanism": "Presence of ANA is a hallmark of SLE.", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12223463" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation impacts immune complex formation.", "mechanism": "Anti-dsDNA antibodies are specific for SLE.", "protein": "Anti-double-stranded DNA (dsDNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12223463" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation affects antibody binding and function.", "mechanism": "Lupus anticoagulant is used to diagnose APS.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12223463" }, { "confidence": "medium", "disease": "Takayasu arteritis", "glycan_involvement": "N-glycosylation modulates IL-6 receptor binding and stability.", "mechanism": "IL-6 is elevated and drives inflammation in TA.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12223463" }, { "confidence": "medium", "disease": "Takayasu arteritis", "glycan_involvement": "Glycosylation affects cytokine secretion and immune signaling.", "mechanism": "IL-12 gene polymorphisms are associated with TA susceptibility.", "protein": "Interleukin-12 (IL-12)", "protein_enriched": { "function": "Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine (PubMed:8605935, PubMed:8943050). IL-12 is primarily produced by professional antigen-presenting cel", "gene_name": "IL12A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P29459" }, "relationship_type": "causal", "source_pmcid": "PMC12223463" }, { "confidence": "medium", "disease": "Takayasu arteritis", "glycan_involvement": "N-glycosylation is critical for antigen presentation.", "mechanism": "HLA polymorphisms increase risk for TA.", "protein": "Human Leukocyte Antigen (HLA-Bw5, HLA-B39.2)", "relationship_type": "causal", "source_pmcid": "PMC12223463" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation regulates VCAM-1 binding to integrins.", "mechanism": "VCAM-1 mediates leukocyte adhesion in vascular inflammation.", "protein": "Vascular cell adhesion molecule-1 (VCAM-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12223463" }, { "confidence": "medium", "disease": "Takayasu arteritis", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "IL-2 gene polymorphisms are linked to TA pathogenesis.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "causal", "source_pmcid": "PMC12223463" }, { "confidence": "high", "disease": "Liver steatosis (MASLD/NAFLD)", "glycan_involvement": "CD36 is a heavily glycosylated transmembrane protein; glycosylation is required for its membrane localization and function.", "mechanism": "Promotes long-chain fatty acid uptake in hepatocytes, contributing to lipid accumulation and steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates CD36 stability and trafficking.", "mechanism": "Upregulated in obesity, enhances fatty acid uptake and storage.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects CD36-mediated signaling.", "mechanism": "Elevated CD36 expression is linked to impaired insulin signaling in metabolic tissues.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "PAI-1 is glycosylated; glycosylation affects its secretion and stability.", "mechanism": "Promotes vascular inflammation and plaque formation.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation regulates PAI-1 activity.", "mechanism": "Elevated PAI-1 levels are associated with adipose tissue inflammation and metabolic dysfunction.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12224049" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "Facilitates uptake of oxidized LDL, contributing to foam cell formation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation modulates CD36 function.", "mechanism": "Increased CD36 expression correlates with metabolic syndrome features.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224049" }, { "confidence": "medium", "disease": "Liver steatosis (MASLD/NAFLD)", "glycan_involvement": "Glycosylation affects PAI-1 stability and activity.", "mechanism": "Promotes hepatic inflammation and fibrosis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC12224049" }, { "confidence": "medium", "disease": "Liver steatosis (MASLD/NAFLD)", "glycan_involvement": "Targeting glycosylation may modulate CD36 activity.", "mechanism": "Downregulation by WGT reduces hepatic lipid accumulation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224049" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for PAI-1 secretion.", "mechanism": "Elevated in obese states, reflects adipose inflammation.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12224049" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IFNAR1 is a glycoprotein; glycosylation affects receptor stability and ligand binding.", "mechanism": "IFNAR1 mediates type I interferon signaling, driving SLE pathogenesis; blockade by anifrolumab reduces inflammation.", "protein": "Interferon alpha receptor 1 (IFNAR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation regulates IFNAR1 cell surface expression and function.", "mechanism": "Plasmacytoid dendritic cells produce type I IFN via IFNAR1, promoting autoimmunity in SLE.", "protein": "Plasmacytoid dendritic cell IFNAR1", "relationship_type": "causal", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Low C3 levels indicate active SLE and complement consumption.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 glycosylation is required for complement activation.", "mechanism": "Low C4 levels are associated with SLE activity and immune complex formation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation modulates antibody effector functions and pathogenicity.", "mechanism": "High anti-dsDNA IgG titers correlate with SLE activity and organ involvement.", "protein": "Anti-dsDNA antibodies (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Anifrolumab glycosylation affects antibody stability and immune effector functions.", "mechanism": "Anifrolumab binds IFNAR1, blocking type I IFN signaling and reducing SLE symptoms.", "protein": "Anifrolumab (therapeutic antibody)", "relationship_type": "therapeutic", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Steroid-dependent SLE", "glycan_involvement": "Glycosylation modulates IFNAR1 function and therapeutic antibody binding.", "mechanism": "IFNAR1 blockade enables reduction/discontinuation of glucocorticoids in steroid-dependent SLE.", "protein": "Interferon alpha receptor 1 (IFNAR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224262" }, { "confidence": "medium", "disease": "Neuropsychiatric SLE", "glycan_involvement": "Glycosylation affects IFNAR1 CNS expression and function.", "mechanism": "IFNAR1 signaling implicated in neuropsychiatric SLE; inhibition may reduce CNS symptoms.", "protein": "Interferon alpha receptor 1 (IFNAR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Glucocorticoid-induced complications (e.g., diabetes, cataracts)", "glycan_involvement": "Antibody glycosylation impacts pharmacokinetics and safety profile.", "mechanism": "Anifrolumab enables GCS withdrawal, reducing risk of steroid-induced complications.", "protein": "Anifrolumab (therapeutic antibody)", "relationship_type": "protective", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation influences pathogenicity and clearance.", "mechanism": "Anti-dsDNA IgG drives immune complex formation and tissue damage in SLE.", "protein": "Anti-dsDNA antibodies (IgG)", "relationship_type": "causal", "source_pmcid": "PMC12224262" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect trafficking and PET ligand binding.", "mechanism": "SV2A PET signal reduction reflects synaptic loss, an early hallmark of AD.", "protein": "SV2A", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "VAMP2 is glycosylated; glycosylation may affect vesicle fusion and release.", "mechanism": "CSF and plasma VAMP2 levels altered in AD; associated with synaptic density and tau pathology.", "protein": "VAMP2", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "Glycosylation may modulate VAMP2 function in vesicle trafficking.", "mechanism": "CSF VAMP2 increased in FTD, reflecting synaptic pathology.", "protein": "VAMP2", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "medium", "disease": "Lewy body dementia", "glycan_involvement": "Glycosylation status may influence VAMP2 interaction with \u03b1-synuclein.", "mechanism": "CSF VAMP2 decreased, possibly due to \u03b1-synuclein-induced sequestration.", "protein": "VAMP2", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Peripheral glycosylation may affect SNAP25 plasma levels.", "mechanism": "CSF SNAP25 elevated in AD, correlates with synaptic loss and APOE-\u025b4 status.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "Glycosylation may modulate SNAP25 function.", "mechanism": "CSF SNAP25 increased in FTD, but less than in AD.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "medium", "disease": "Creutzfeldt-Jakob disease", "glycan_involvement": "Not specified.", "mechanism": "CSF SNAP25 highly elevated due to rapid synaptic destruction.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is not a glycoprotein; no direct glycan involvement.", "mechanism": "Plasma GFAP elevated in AD, reflects astrocyte reactivity and synaptic loss.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "No direct glycan involvement.", "mechanism": "GFAP elevated, predicts dementia progression, but less specific than in AD.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "high", "disease": "Normal aging", "glycan_involvement": "Glycosylation may affect VAMP2 stability and detection.", "mechanism": "Plasma VAMP2 levels reflect synaptic density independent of age and neurodegeneration.", "protein": "VAMP2", "relationship_type": "biomarker", "source_pmcid": "PMC12225678" }, { "confidence": "high", "disease": "End-Stage Renal Disease", "glycan_involvement": "FGF-23 is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "FGF-23 levels are elevated in ESRD and correlate with disease progression and prognosis.", "protein": "Fibroblast Growth Factor 23", "protein_enriched": { "function": "Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By si", "gene_name": "FGF23", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9GZV9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Mineral Bone Disease", "glycan_involvement": "Glycosylation affects FGF-23 bioactivity and clearance.", "mechanism": "FGF-23 regulates phosphate metabolism, contributing to CKD-related mineral bone abnormalities.", "protein": "Fibroblast Growth Factor 23", "protein_enriched": { "function": "Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By si", "gene_name": "FGF23", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9GZV9" }, "relationship_type": "causal", "source_pmcid": "PMC12225695" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates FGF-23 stability and receptor interactions.", "mechanism": "Elevated FGF-23 is associated with increased risk of CVD (e.g., left ventricular hypertrophy, arrhythmias) in CKD/ESRD.", "protein": "Fibroblast Growth Factor 23", "protein_enriched": { "function": "Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By si", "gene_name": "FGF23", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9GZV9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Hyperphosphatemia", "glycan_involvement": "Glycosylation required for FGF-23 secretion.", "mechanism": "FGF-23 inhibits renal phosphate reabsorption; in ESRD, its effect is blunted, leading to hyperphosphatemia.", "protein": "Fibroblast Growth Factor 23", "protein_enriched": { "function": "Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By si", "gene_name": "FGF23", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9GZV9" }, "relationship_type": "causal", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Renal Hyperparathyroidism", "glycan_involvement": "PTH is glycosylated; glycosylation affects its stability and activity.", "mechanism": "Elevated iPTH is a marker and driver of renal hyperparathyroidism in CKD/ESRD.", "protein": "Intact Parathyroid Hormone", "protein_enriched": { "function": "Parathyroid hormone elevates calcium level by dissolving the salts in bone and preventing their renal excretion (PubMed:11604398, PubMed:35932760). Acts by binding to its receptor, PTH1R, activating G", "gene_name": "PTH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01270" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Mineral Bone Disease", "glycan_involvement": "Glycosylation modulates PTH secretion and function.", "mechanism": "High iPTH contributes to bone metabolism abnormalities in CKD-MBD.", "protein": "Intact Parathyroid Hormone", "protein_enriched": { "function": "Parathyroid hormone elevates calcium level by dissolving the salts in bone and preventing their renal excretion (PubMed:11604398, PubMed:35932760). Acts by binding to its receptor, PTH1R, activating G", "gene_name": "PTH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01270" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Not applicable (not a glycoprotein).", "mechanism": "Elevated Hcy is an independent risk factor for CVD in CKD/ESRD patients.", "protein": "Homocysteine", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12225695" }, { "confidence": "medium", "disease": "End-Stage Renal Disease", "glycan_involvement": "Not applicable.", "mechanism": "High Hcy levels correlate with renal dysfunction and progression to ESRD.", "protein": "Homocysteine", "relationship_type": "biomarker", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation required for FGF-23 secretion.", "mechanism": "FGF-23 levels rise as CKD progresses; useful for early detection and monitoring.", "protein": "Fibroblast Growth Factor 23", "protein_enriched": { "function": "Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By si", "gene_name": "FGF23", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9GZV9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation affects PTH function.", "mechanism": "iPTH levels increase with CKD progression; used for monitoring and management.", "protein": "Intact Parathyroid Hormone", "protein_enriched": { "function": "Parathyroid hormone elevates calcium level by dissolving the salts in bone and preventing their renal excretion (PubMed:11604398, PubMed:35932760). Acts by binding to its receptor, PTH1R, activating G", "gene_name": "PTH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01270" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225695" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "vWF is a heavily glycosylated protein; glycosylation is essential for its stability, multimerization, and function.", "mechanism": "Deficiency or qualitative defect in vWF impairs platelet adhesion and aggregation, leading to bleeding.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12225761" }, { "confidence": "high", "disease": "Hemorrhagic complications in oral surgery", "glycan_involvement": "Glycosylation of vWF is critical for its interaction with platelets and subendothelial collagen.", "mechanism": "Reduced or defective vWF leads to impaired hemostasis during surgical procedures.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12225761" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Both vWF and FVIII are glycoproteins; glycosylation affects their plasma half-life and activity.", "mechanism": "vWF stabilizes circulating Factor VIII; vWF deficiency leads to secondary reduction in FVIII.", "protein": "Factor VIII", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12225761" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Assays detect total and functional glycosylated vWF.", "mechanism": "vWF antigen and activity assays are diagnostic for vWD.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12225761" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Therapeutic vWF must be properly glycosylated for efficacy.", "mechanism": "Replacement therapy with vWF-containing concentrates corrects bleeding tendency.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225761" }, { "confidence": "high", "disease": "Respiratory tract infections (RTIs)", "glycan_involvement": "Glycosylation facilitates host cell binding and immune evasion.", "mechanism": "Mediates viral attachment to host cells and suppresses innate immune responses.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Respiratory tract infections (RTIs)", "glycan_involvement": "Glycosylation affects immunogenicity and neutralizing antibody response.", "mechanism": "Promotes fusion of viral and host cell membranes, enabling viral entry.", "protein": "Fusion protein F", "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Facilitates viral spread in lower respiratory tract, leading to bronchiolitis.", "protein": "Fusion protein F", "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Reinfection", "glycan_involvement": "Glycosylation aids immune evasion.", "mechanism": "Suppresses innate immunity and inhibits TLR/PRR signaling, allowing recurrent infections.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation influences antigenicity and immune response.", "mechanism": "Drives viral entry and cell-to-cell transmission in lung tissue.", "protein": "Fusion protein F", "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "medium", "disease": "Asthma exacerbation", "glycan_involvement": "Glycosylation may affect receptor interactions and immune modulation.", "mechanism": "Triggers inflammatory cytokine release (IL-33, TSLP), worsening asthma.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "medium", "disease": "Respiratory tract infections (RTIs)", "glycan_involvement": "Glycosylation status affects immunogenicity.", "mechanism": "Contributes to viral entry and immune modulation.", "protein": "Small hydrophobic protein SH", "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Vaccine response", "glycan_involvement": "Glycosylation critical for antigenicity and vaccine efficacy.", "mechanism": "Highly immunogenic; induces neutralizing antibodies in vaccine studies.", "protein": "Fusion protein F", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Vaccine response", "glycan_involvement": "Glycosylation may reduce immunogenicity.", "mechanism": "Low antigenicity; insufficient neutralizing antibody production in vaccine studies.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225965" }, { "confidence": "medium", "disease": "Immunosuppression-related complications", "glycan_involvement": "Glycosylation may affect immune escape.", "mechanism": "Facilitates infection in immunocompromised hosts, leading to severe disease.", "protein": "Fusion protein F", "relationship_type": "causal", "source_pmcid": "PMC12225965" }, { "confidence": "high", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation critical for protein stability and crystal interaction.", "mechanism": "Binds free calcium ions and coats CaOx crystals, inhibiting crystallization, growth, aggregation, and cell adhesion.", "protein": "Uromodulin (Tamm-Horsfall protein)", "protein_enriched": { "function": "Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like stru", "gene_name": "UMOD", "glycan_count": 403, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G60554YG", "G74722FL", "G00273SJ", "G00912UN", "G03895SR", "G04854VP", "G06356OH", "G08918WF", "G09118YK", "G10846ZT", "G11041DA", "G11629QQ", "G11671GQ", "G12222NC", "G12261QD", "G12793SR", "G14047PA", "G14972EH", "G15169WU", "G15664MX", "G16774YZ", "G17540HT", "G17689DH", "G19469VZ", "G19603RR", "G20528HD", "G20706XG", "G22310AV", "G23345GE", "G24413UY", "G26403SG", "G26935KA", "G28681TP", "G29676WX", "G31309XD", "G31532GK", "G31685JQ", "G32659RY", "G33241WC", "G36191CD", "G36442WJ", "G37412TK", "G38022PE", "G39595FH", "G40206WX", "G40554DX", "G40574BA", "G40926MX", "G41882MT", "G41981MA", "G43223CG", "G43669FQ", "G44305KR", "G45395BF", "G45560HM", "G46185ND", "G46503DX", "G46665ZP", "G46902YN", "G47007PV", "G47012YE", "G47518TP", "G47975JA", "G48414YA", "G48584BU", "G49018RC", "G49305IN", "G49589RB", "G49642SA", "G50427EO", "G50856PC", "G51098AA", "G52527GH", "G52676LZ", "G53752TA", "G54010QB", "G54018RP", "G56318NV", "G56499YQ", "G57565TQ", "G57835AK", "G57955DP", "G59536GA", "G60227QI", "G60439QY", "G61256FT", "G62765YT", "G63136LV", "G63980BQ", "G65414LI", "G65449BO", "G66088HZ", "G66937TJ", "G67173FM", "G68668TB", "G68873DS", "G69170UT", "G69521XL", "G69834CE", "G70888PK", "G71906BW", "G72735IY", "G72747WU", "G75120WS", "G75418YA", "G75607BQ", "G75983OB", "G76294TY", "G76295SF", "G77252PU", "G77669RF", "G78030KJ", "G78787DI", "G79565XA", "G79666IR", "G80319WU", "G80920RR", "G80966KZ", "G81124ET", "G81198YO", "G82811EP", "G82894XV", "G84349RE", "G87123QX", "G89045VA", "G90542MP", "G90987JA", "G91365ZQ", "G91413ZX", "G91473PK", "G92135MA", "G92551JA", "G92681HQ", "G92974UU", "G93656SY", "G94047VH", "G94470IW", "G94531EZ", "G94876HV", "G95977AE", "G96430BV", "G96921ZU", "G98129XB", "G98611JV", "G99808VS", "G60145BJ", "G00433UK", "G05724UK", "G06110VR", "G14456RI", "G23432EQ", "G23863VK", "G35697OJ", "G39188ZX", "G46687AB", "G49874UX", "G50045TK", "G55220VL", "G64527OM", "G65092SV", "G66538GV", "G74430RZ", "G76329HL", "G93683YO", "G22355FZ", "G22625SJ", "G01485JJ", "G05813WO", "G05962QB", "G08290VR", "G11115RO", "G11611PG", "G12341GU", "G13191RB", "G23811SR", "G27058EU", "G27322BI", "G29972TM", "G31852PQ", "G34617SM", "G34989PA", "G37773JL", "G37881RL", "G39471UU", "G41247ZX", "G42459UQ", "G47644PP", "G48488CO", "G49084LP", "G49739MP", "G52848YE", "G53075ES", "G53193KA", "G57581QG", "G57776ZS", "G64275UO", "G64394MX", "G65540UB", "G67164EE", "G70223PD", "G70232NH", "G71463BG", "G72197KC", "G72886NH", "G73027HY", "G74381CZ", "G77023TY", "G78649WQ", "G78726CB", "G80075MS", "G81637OR", "G82443XX", "G83460ZZ", "G84735GS", "G87399DK", "G90093AU", "G90382BL", "G90787TS", "G93718GY", "G94310CV", "G94665LC", "G95046LV", "G20425TQ", "G22768VO", "G24420RT", "G46638GC", "G59626AS", "G60033FS", "G64652EG", "G76882CO", "G81315DD", "G88219FI", "G46524LG", "G47681UP", "G85228QD", "G01160VV", "G02315DX", "G02628JF", "G02815KT", "G02886BB", "G03693IY", "G04657PL", "G04672QB", "G05049YU", "G06247RL", "G06330RB", "G07246CJ", "G07755XJ", "G10486CT", "G10819WX", "G11314AS", "G11870QZ", "G13131HA", "G14547CB", "G15488CF", "G16125XL", "G17208MA", "G18590ZR", "G18804KX", "G19116TW", "G20312EM", "G23505EP", "G23719VF", "G24835MQ", "G25379SA", "G25418HZ", "G26101XB", "G26759AS", "G27126ED", "G27516OE", "G27915IV", "G27947YN", "G28622IK", "G29299MO", "G29501UT", "G29545VG", "G30248BL", "G30740WO", "G30751OD", "G30799SW", "G30970QQ", "G31615DN", "G31973KL", "G31986NC", "G32788FZ", "G33416PL", "G35253PZ", "G35541EV", "G37399XV", "G37692EO", "G37818NZ", "G37995HC", "G39064KU", "G39446WN", "G39619TI", "G39643OJ", "G40834TG", "G41071NU", "G42124LM", "G43734MM", "G44173IH", "G44753VC", "G45504EY", "G46487SG", "G46691LC", "G46842SD", "G47950XN", "G49755GI", "G50457PU", "G51653BI", "G52358QA", "G54612UD", "G54740VA", "G55132BD", "G56087PR", "G57888GL", "G58087IP", "G58954YZ", "G59324HL", "G59924QI", "G60834IK", "G60967DT", "G61011OB", "G61053JL", "G61806WR", "G62461SM", "G64409MC", "G65000LJ", "G66621EA", "G66760KM", "G67900CJ", "G68490OW", "G68833MP", "G70101JE", "G70441OD", "G70619PT", "G70822IO", "G72398FA", "G72797UR", "G73968GN", "G75256KV", "G75568BH", "G76915KR", "G77547TA", "G78701GW", "G81263BG", "G81375TC", "G81976CN", "G82348BZ", "G82830MN", "G83646BJ", "G84452RH", "G84862VB", "G85282JO", "G85554PZ", "G85677PP", "G86182NS", "G86880BF", "G87661QW", "G88891KO", "G89098OM", "G90335NR", "G90659AW", "G92275SC", "G92406TI", "G96416FQ", "G96577RX", "G99198RV", "G99668VU", "G99679NM", "G99966GV", "G71142DF", "G02620FP", "G03622KA", "G09285QR", "G13238MZ", "G16265OF", "G20014JD", "G23092XT", "G28209TJ", "G28975ZZ", "G40843RG", "G45841FE", "G46422KL", "G49356OF", "G50911BZ", "G54330GJ", "G57097ZE", "G62168IR", "G64160PL", "G65766QU", "G67596QA", "G69560OI", "G72755ZH", "G75325GX", "G80961YY", "G82233NS", "G83487DQ", "G87932HN", "G94222SG", "G94788LD", "G98846QS", "G99025FY" ], "uniprot_id": "P07911" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "high", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation may affect secretion and inhibitory function.", "mechanism": "Inhibits CaOx crystal formation and growth; highest relative inhibitory activity in urine fractions.", "protein": "Protein AMBP", "protein_enriched": { "function": "Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extr", "gene_name": "AMBP", "glycan_count": 104, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G04854VP", "G06247RL", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G18647XP", "G20528HD", "G23505EP", "G27058EU", "G31986NC", "G33416PL", "G37412TK", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G47644PP", "G48414YA", "G50045TK", "G57317CE", "G58087IP", "G59324HL", "G59626AS", "G61256FT", "G63980BQ", "G64527OM", "G68490OW", "G70232NH", "G70619PT", "G72747WU", "G77669RF", "G85282JO", "G86182NS", "G87389XI", "G92551JA", "G94470IW", "G95865ZB", "G98611JV", "G17015OC", "G25426PD", "G43417UB", "G58001LT", "G02030ZB", "G02628JF", "G02815KT", "G04672QB", "G05049YU", "G06010PM", "G06356OH", "G07246CJ", "G08290VR", "G10819WX", "G12579WK", "G14972EH", "G15569GG", "G20425TQ", "G22625SJ", "G24954UD", "G26330YA", "G27516OE", "G27915IV", "G28541PG", "G28681TP", "G30970QQ", "G32259BI", "G34423JR", "G35029YA", "G37995HC", "G40926MX", "G44173IH", "G44215PV", "G46902YN", "G49018RC", "G49906RN", "G54010QB", "G57776ZU", "G58954YZ", "G59536GA", "G60177UT", "G64275UO", "G64409MC", "G66163OV", "G70375MX", "G75256KV", "G75983OB", "G76613WN", "G77547TA", "G78787DI", "G82830MN", "G84862VB", "G85269DF", "G86226EA", "G12728EY", "G22355FZ", "G31936TA", "G49108TO" ], "uniprot_id": "P02760" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "high", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation influences protein folding and activity.", "mechanism": "Urinary prothrombin fragment 1 adsorbs to crystal surfaces, modulating nucleation and growth.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "high", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation affects protein interactions with crystals.", "mechanism": "Known inhibitor of CaOx stone formation; modulates crystal growth and aggregation.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "high", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Reduces CaOx crystal formation; experimental evidence supports inhibitory role.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "medium", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "O-glycosylation modulates mucosal protection and protein function.", "mechanism": "Inhibits CaOx stone formation; lower levels in stone patients.", "protein": "Trefoil factor 1", "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "medium", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation affects calcium binding and stability.", "mechanism": "Binds calcium ions, present in stone matrix, inhibits crystal formation.", "protein": "Apolipoprotein D", "protein_enriched": { "function": "APOD occurs in the macromolecular complex with lecithin-cholesterol acyltransferase. It is probably involved in the transport and binding of bilin. Appears to be able to transport a variety of ligands", "gene_name": "APOD", "glycan_count": 216, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02315DX", "G03644CB", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G07810QS", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G10846ZT", "G11115RO", "G11629QQ", "G11911BT", "G13694XX", "G13728QT", "G14547CB", "G14669DU", "G15169WU", "G18647XP", "G20312EM", "G20425TQ", "G23294PN", "G23453IV", "G23863VK", "G24835MQ", "G25451PN", "G26330YA", "G26403SG", "G27947YN", "G28681TP", "G31596VW", "G31916IQ", "G35029YA", "G37818NZ", "G38663NM", "G39446WN", "G39595FH", "G40574BA", "G40926MX", "G41882MT", "G44215PV", "G44753VC", "G45504EY", "G46450MZ", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G49755GI", "G49955PK", "G50045TK", "G50427EO", "G52527GH", "G55383ZG", "G56518TU", "G56784JY", "G57317CE", "G57776ZU", "G57888GL", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60177UT", "G62461SM", "G63041LO", "G64394MX", "G64527OM", "G65019XG", "G65184UU", "G66088HZ", "G66537LK", "G70101JE", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G74724QE", "G75983OB", "G76868JS", "G77547TA", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G82830MN", "G83633GK", "G83646BJ", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G86182NS", "G86795LJ", "G86880BF", "G89098OM", "G90734RJ", "G92050GC", "G92081HT", "G92135MA", "G92275SC", "G92551JA", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G99679NM", "G49108TO", "G00406II", "G01521EA", "G02628JF", "G02815KT", "G02886BB", "G03461SC", "G04657PL", "G05049YU", "G05962QB", "G06330RB", "G07799LX", "G08110WX", "G08146BT", "G08290VR", "G08293MJ", "G09831WQ", "G10339FR", "G11314AS", "G11870QZ", "G13191RB", "G14972EH", "G15664MX", "G16125XL", "G22140GZ", "G22310AV", "G23719VF", "G25079LO", "G25418HZ", "G26915XM", "G27058EU", "G27126ED", "G29299MO", "G29880MM", "G31118FR", "G31433PN", "G31936TA", "G32788FZ", "G32926LW", "G33416PL", "G33609NS", "G34617SM", "G35541EV", "G36379GD", "G37399XV", "G37692EO", "G40177UP", "G40834TG", "G41044JW", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G44211QA", "G45395BF", "G46691LC", "G47012YE", "G47644PP", "G47950XN", "G49018RC", "G49589RB", "G49739MP", "G51413EV", "G51640FO", "G57776ZS", "G59324HL", "G62765YT", "G66621EA", "G67164EE", "G68040BX", "G68833MP", "G69834CE", "G70232NH", "G70441OD", "G71560PC", "G72791KH", "G72797UR", "G73686WG", "G75607BQ", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G81637OR", "G82119TF", "G82592ZH", "G83555HU", "G84349RE", "G85144OK", "G85677PP", "G86408JD", "G86752LQ", "G87051GH", "G87123QX", "G88061BX", "G88374WZ", "G89205CJ", "G90093AU", "G90659AW", "G93718GY", "G94917XT", "G95046LV", "G98129XB" ], "uniprot_id": "P05090" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "medium", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation may regulate inhibitory function.", "mechanism": "High inhibitory activity against CaOx crystals; levels decrease in kidney injury and dysfunction.", "protein": "Kininogen-1", "protein_enriched": { "function": "Kininogens are inhibitors of thiol proteases. HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; HMW-kininogen ", "gene_name": "KNG1", "glycan_count": 190, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G53434XO", "G17015OC", "G23729WG", "G29068FM", "G43417UB", "G57317CE", "G58001LT", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11115RO", "G11629QQ", "G11911BT", "G12261QD", "G12793SR", "G15169WU", "G20425TQ", "G20706XG", "G22140GZ", "G22276PO", "G23505EP", "G25079LO", "G26267FS", "G26330YA", "G27947YN", "G30248BL", "G30740WO", "G30769VJ", "G33416PL", "G36131WL", "G37692EO", "G40206WX", "G40574BA", "G40926MX", "G43223CG", "G44576HQ", "G44753VC", "G47012YE", "G47518TP", "G48414YA", "G50045TK", "G52527GH", "G52890YB", "G58954YZ", "G59626AS", "G61256FT", "G62165AG", "G63136LV", "G63980BQ", "G66088HZ", "G66163OV", "G69834CE", "G70232NH", "G70888PK", "G72747WU", "G72797UR", "G77669RF", "G78644BR", "G79286RS", "G79666IR", "G82830MN", "G85144OK", "G86752LQ", "G87123QX", "G87389XI", "G89045VA", "G90093AU", "G92551JA", "G94470IW", "G94917XT", "G95678HJ", "G98129XB", "G99679NM", "G00273SJ", "G01485JJ", "G07246CJ", "G08293MJ", "G09831WQ", "G10846ZT", "G11314AS", "G11870QZ", "G14547CB", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G24377DY", "G27058EU", "G27126ED", "G27915IV", "G28681TP", "G31852PQ", "G32788FZ", "G33791AF", "G40834TG", "G42124LM", "G45395BF", "G45504EY", "G53075ES", "G56518TU", "G56784JY", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G60967DT", "G61806WR", "G62765YT", "G64409MC", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G76417NN", "G77547TA", "G78649WQ", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G84452RH", "G84862VB", "G85269DF", "G86182NS", "G86795LJ", "G86880BF", "G88374WZ", "G90659AW", "G92081HT", "G92135MA", "G92275SC", "G95865ZB", "G96091TT", "G98611JV", "G99668VU", "G03644CB", "G04657PL", "G07810QS", "G08110WX", "G10819WX", "G12341GU", "G13910DJ", "G15488CF", "G18590ZR", "G23811SR", "G23863VK", "G26377UA", "G26403SG", "G30221QT", "G31118FR", "G34989PA", "G37818NZ", "G39170TE", "G39595FH", "G41346UA", "G42358LZ", "G43669FQ", "G43734MM", "G44778BV", "G46665ZP", "G47644PP", "G47737VJ", "G54010QB", "G57471MV", "G60033FS", "G64394MX", "G72667IM", "G75983OB", "G76329HL", "G76915KR", "G81124ET", "G81198YO", "G90382BL", "G92406TI", "G93683YO", "G97968CT", "G57321FI", "G36379GD", "G46691LC", "G73004SD", "G74722FL", "G10019LZ", "G23010ZW", "G38663NM", "G43089EG", "G57888GL", "G62461SM" ], "uniprot_id": "P01042" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "medium", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation essential for anti-aggregation activity.", "mechanism": "Inhibits CaOx crystal aggregation and cell adhesion.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "medium", "disease": "Calcium oxalate kidney stone (nephrolithiasis)", "glycan_involvement": "N-glycosylation influences secretion and activity.", "mechanism": "Novel inhibitor; may regulate crystal growth via epithelial cell signaling.", "protein": "Pro-epidermal growth factor", "protein_enriched": { "function": "EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the", "gene_name": "EGF", "glycan_count": 12, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G02815KT", "G05724UK", "G31852PQ", "G62765YT", "G64527OM", "G80920RR", "G82020ZR", "G83460ZZ", "G49108TO", "G71142DF", "G43417UB", "G53434XO" ], "uniprot_id": "P01133" }, "relationship_type": "protective", "source_pmcid": "PMC12226074" }, { "confidence": "high", "disease": "Hypercoagulopathy", "glycan_involvement": "MTHFR is a glycoprotein; glycosylation may affect enzyme stability and activity.", "mechanism": "MTHFR mutation disrupts folate/homocysteine metabolism, elevating homocysteine and promoting endothelial dysfunction and clot formation.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "high", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation may modulate MTHFR function.", "mechanism": "Elevated homocysteine due to MTHFR mutation increases risk of venous thrombosis.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "high", "disease": "Pulmonary embolism (PE)", "glycan_involvement": "Glycosylation status may affect enzyme activity.", "mechanism": "Impaired homocysteine metabolism leads to hypercoagulable state and increased PE risk.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may influence MTHFR stability.", "mechanism": "Elevated homocysteine from MTHFR mutation causes endothelial dysfunction, contributing to cardiovascular pathology.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Anencephaly", "glycan_involvement": "Glycosylation may affect enzyme folding and function.", "mechanism": "MTHFR mutation impairs folate metabolism, increasing risk of neural tube defects.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Spina bifida", "glycan_involvement": "Glycosylation may impact enzyme activity.", "mechanism": "Defective folate metabolism due to MTHFR mutation increases risk of neural tube defects.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Homocystinuria", "glycan_involvement": "Glycosylation may affect enzyme function.", "mechanism": "MTHFR mutation leads to accumulation of homocysteine.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "low", "disease": "Malignancy", "glycan_involvement": "Glycosylation may influence enzyme stability.", "mechanism": "MTHFR mutation associated with increased risk of certain cancers.", "protein": "Methylenetetrahydrofolate reductase (MTHFR)", "protein_enriched": { "function": "Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connec", "gene_name": "MTHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42898" }, "relationship_type": "risk factor", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Hypercoagulopathy", "glycan_involvement": "Factor VIII is heavily glycosylated; glycosylation affects secretion and activity.", "mechanism": "Elevated factor VIII levels may modify risk of recurrent thrombosis in MTHFR mutation carriers.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12226099" }, { "confidence": "medium", "disease": "Homocystinuria", "glycan_involvement": "Methionine synthase is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Requires 5-methyltetrahydrofolate from MTHFR for homocysteine conversion; impaired function leads to homocystinuria.", "protein": "Methionine synthase", "protein_enriched": { "function": "Regulatory subunit which plays a role in the allosteric regulation of the enzyme catalyzing the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH", "gene_name": "IDH3G", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51553" }, "relationship_type": "causal", "source_pmcid": "PMC12226099" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG trigger CNS demyelination via immune-mediated attack on oligodendrocytes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG may influence antibody recognition.", "mechanism": "Serum anti-MOG IgG is diagnostic for MOGAD and used for disease monitoring.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226104" }, { "confidence": "medium", "disease": "Transverse Myelitis (TM)", "glycan_involvement": "Glycosylation may modulate immune response to MOG.", "mechanism": "Anti-MOG antibodies can cause TM, often with neurogenic bladder/urinary dysfunction.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "high", "disease": "Optic Neuritis (ON)", "glycan_involvement": "Glycosylation may affect MOG antigenicity.", "mechanism": "Anti-MOG antibodies frequently cause ON, leading to visual loss and pain.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "medium", "disease": "Acute Disseminated Encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "Anti-MOG antibodies implicated in ADEM, causing cortical and brainstem inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Anti-AQP4 antibodies cause NMOSD via astrocyte damage and demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation differences may contribute to disease specificity.", "mechanism": "Anti-MOG antibodies distinguish MOGAD from MS; MS typically lacks anti-MOG antibodies.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12226104" }, { "confidence": "medium", "disease": "Urinary retention (neurogenic bladder)", "glycan_involvement": "Glycosylation may modulate MOG's immunogenicity.", "mechanism": "MOGAD can present with acute urinary retention due to CNS lesions affecting autonomic pathways.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "medium", "disease": "Relapsing demyelinating syndromes", "glycan_involvement": "Glycosylation may affect antibody persistence.", "mechanism": "Persistence of anti-MOG antibodies correlates with risk of relapse.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226104" }, { "confidence": "low", "disease": "Post-infectious demyelination", "glycan_involvement": "Glycosylation may influence immune response post-infection.", "mechanism": "Infections (e.g., Borrelia, herpes) may trigger anti-MOG antibody production and demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12226104" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "SiglecF binds sialylated glycans, mediating cell-cell interactions and signaling.", "mechanism": "SiglecF+ neutrophils promote Th17 differentiation and suppress Treg development, exacerbating neuroinflammation.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "SiglecF recognizes sialylated glycan ligands, influencing immune cell function.", "mechanism": "SiglecF+ neutrophils drive Th17-mediated pathology; depletion reduces disease severity.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "SiglecF-glycan interactions modulate neutrophil activity.", "mechanism": "SiglecF+ neutrophils exhibit pro-fibrotic phenotypes.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "SiglecF binds tumor-associated sialylated glycans.", "mechanism": "SiglecF+ neutrophils promote tumor growth via immunosuppressive phenotype.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Airway inflammation", "glycan_involvement": "SiglecF-glycan binding modulates neutrophil function.", "mechanism": "SiglecF+ neutrophils enhance Th2/Th17 responses.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "SiglecF recognizes airway sialylated glycans.", "mechanism": "SiglecF+ neutrophils contribute to airway inflammation.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "SiglecF-glycan interactions regulate neutrophil phenotype.", "mechanism": "SiglecF+ neutrophils arise during immunosuppressed phase, modulating inflammation.", "protein": "SiglecF", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "Prg4", "glycan_count": 2, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9JM99" }, "relationship_type": "protective/immunosuppressive", "source_pmcid": "PMC12226254" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "MOG acts as autoantigen targeted by autoreactive T cells.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "IL-6R\u03b1 is glycosylated, affecting receptor stability and signaling.", "mechanism": "IL-6R\u03b1 on SiglecF+ neutrophils enables trans-signaling, promoting Th17 responses.", "protein": "IL-6 receptor alpha (IL-6R\u03b1)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of ", "gene_name": "Il6ra", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G25079LO" ], "uniprot_id": "P22272" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "IL-23R is glycosylated, modulating receptor function.", "mechanism": "IL-23R signaling in neutrophils and T cells drives pathogenic Th17 differentiation.", "protein": "IL-23 receptor", "protein_enriched": { "function": "Peptidyl-tRNA hydrolase which releases tRNAs from the ribosome during protein synthesis. Promotes caspase-independent apoptosis by regulating the function of two transcriptional regulators, AES and TL", "gene_name": "Ptrh2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8R2Y8" }, "relationship_type": "causal", "source_pmcid": "PMC12226254" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Promotes tumor growth, EMT, chemoresistance via JAK/STAT3 and MAPK pathways.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects IL-6 secretion and receptor binding.", "mechanism": "Induces CSC expansion, metastasis, and resistance via STAT3 activation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "IL-6R\u03b1 is glycosylated; glycosylation affects receptor shedding and function.", "mechanism": "Trans-signaling via soluble IL-6R\u03b1 promotes tumorigenesis, especially in colitis-associated cancer.", "protein": "IL-6 receptor alpha (IL-6R\u03b1)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of ", "gene_name": "Il6ra", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G25079LO" ], "uniprot_id": "P22272" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "gp130 is glycosylated; glycosylation required for cell surface expression.", "mechanism": "Signal transduction for IL-6 family cytokines, driving tumor growth and chemoresistance.", "protein": "gp130 (IL6ST)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Indirect; STAT3 activation downstream of glycoprotein receptors.", "mechanism": "Constitutive activation by IL-6/JAK pathway drives EMT, metastasis, and drug resistance.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "medium", "disease": "Prostate carcinoma", "glycan_involvement": "IL-35 is a heterodimeric glycoprotein; glycosylation affects secretion.", "mechanism": "Promotes angiogenesis, proliferation, and immune suppression via Treg and MDSC expansion.", "protein": "IL-35", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12226255" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Putative glycoprotein; glycosylation likely affects stability.", "mechanism": "Promotes colony formation and proliferation in pancreatic cancer cells.", "protein": "IL-39", "relationship_type": "causal", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "VEGF is glycosylated; glycosylation required for activity.", "mechanism": "IL-6 upregulates VEGF, promoting angiogenesis and tumor progression.", "protein": "VEGF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226255" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "OSM is glycosylated; glycosylation required for secretion.", "mechanism": "Promotes EMT, metastasis, and CSC maintenance via STAT3.", "protein": "Oncostatin M (OSM)", "protein_enriched": { "function": "Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothe", "gene_name": "OSM", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13725" }, "relationship_type": "causal", "source_pmcid": "PMC12226255" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "IL-6 glycosylation affects secretion and stability in CNS.", "mechanism": "High IL-6 levels linked to neuroinflammation, cognitive decline, and microglial activation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226255" }, { "confidence": "high", "disease": "Nairobi sheep disease", "glycan_involvement": "Envelope glycoprotein likely glycosylated, mediating host cell attachment and immune evasion", "mechanism": "NSDV glycoprotein mediates viral entry and host specificity, causing hemorrhagic fever in sheep", "protein": "NSDV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "high", "disease": "Human febrile illness (NSDV)", "glycan_involvement": "Glycosylation may affect host range and immune recognition", "mechanism": "NSDV glycoprotein enables zoonotic infection in humans, causing febrile illness", "protein": "NSDV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "medium", "disease": "Human febrile illness (JMTV)", "glycan_involvement": "Envelope glycoprotein likely glycosylated, facilitating host cell entry", "mechanism": "JMTV glycoprotein mediates infection in humans, associated with febrile disease", "protein": "JMTV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "medium", "disease": "Animal febrile illness (LTV)", "glycan_involvement": "Glycosylation may contribute to host adaptation", "mechanism": "LTV glycoprotein mediates infection in ruminants (cattle, sheep)", "protein": "LTV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "medium", "disease": "Human febrile illness (Tamdy orthonairovirus/Songling virus)", "glycan_involvement": "Likely glycosylated, mediating host cell entry", "mechanism": "Tamdy orthonairovirus glycoprotein implicated in zoonotic transmission and human febrile illness", "protein": "Tamdy orthonairovirus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "low", "disease": "Animal febrile illness (Kismayo virus)", "glycan_involvement": "Envelope glycoprotein likely glycosylated", "mechanism": "Kismayo virus glycoprotein mediates infection in animals; potential zoonotic risk", "protein": "Kismayo virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "low", "disease": "Animal febrile illness (BDTPV-2)", "glycan_involvement": "Envelope glycoprotein likely glycosylated", "mechanism": "BDTPV-2 glycoprotein mediates infection in dogs", "protein": "Brown dog tick phlebovirus-2 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "high", "disease": "Viral evolution/host adaptation", "glycan_involvement": "No direct glycan involvement; affects viral glycoprotein sequence evolution", "mechanism": "APOBEC edits viral RNA, restricting replication and driving viral evolution", "protein": "APOBEC", "protein_enriched": { "function": "Cytidine deaminase catalyzing the cytidine to uridine postranscriptional editing of a variety of mRNAs (PubMed:30844405). Form complexes with cofactors that confer differential editing activity and se", "gene_name": "APOBEC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41238" }, "relationship_type": "protective", "source_pmcid": "PMC12226380" }, { "confidence": "high", "disease": "Viral evolution/host adaptation", "glycan_involvement": "No direct glycan involvement; may alter glycoprotein coding sequence", "mechanism": "ADAR edits viral RNA, promoting A-to-G transitions and viral adaptation", "protein": "ADAR", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene ex", "gene_name": "ADAR", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P55265" }, "relationship_type": "protective", "source_pmcid": "PMC12226380" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever", "glycan_involvement": "Heavily glycosylated envelope glycoprotein critical for infectivity and immune evasion", "mechanism": "CCHFV glycoprotein mediates viral entry and pathogenesis in humans", "protein": "CCHFV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12226380" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Activates hepatic stellate cells (HSCs), promoting ECM deposition and fibrosis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12226408" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Hydroxylation and glycosylation essential for fibril formation.", "mechanism": "Major ECM component accumulated during fibrosis.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226408" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not glycosylated; indirect involvement via ECM interaction.", "mechanism": "Marker of activated HSCs/myofibroblasts in fibrotic tissue.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Contains O-glycosylation sites; may affect protein stability.", "mechanism": "Accumulation indicates impaired autophagic flux in activated HSCs.", "protein": "p62", "relationship_type": "biomarker", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "No direct glycosylation; involved in autophagy machinery.", "mechanism": "LC3-II accumulation reflects autophagosome formation; increased in impaired autophagy.", "protein": "LC3", "relationship_type": "biomarker", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "No direct glycosylation; involved in autophagy.", "mechanism": "Downregulation associated with defective autophagosome formation in fibrosis.", "protein": "Atg5", "protein_enriched": { "function": "Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme,", "gene_name": "ATG5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H1Y0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "No direct glycosylation; involved in autophagy.", "mechanism": "Deficiency impairs autophagy, contributing to fibrogenesis.", "protein": "Atg7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may regulate nuclear translocation.", "mechanism": "Activation promotes inflammatory and fibrogenic signaling in HSCs.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "causal", "source_pmcid": "PMC12226408" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for enzyme stability and activity.", "mechanism": "Inhibition by aspirin suppresses HSC activation and promotes autophagy.", "protein": "COX-1/2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226408" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates receptor interaction and signaling.", "mechanism": "Chronic activation drives progression from fibrosis to HCC.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12226408" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies (lupus anticoagulant, anticardiolipin) target beta-2 glycoprotein 1, promoting thrombosis and pregnancy morbidity.", "protein": "beta-2 glycoprotein 1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226965" }, { "confidence": "high", "disease": "Chronic Liver Disease/Cirrhosis", "glycan_involvement": "Glycosylation modulates vWF function and clearance.", "mechanism": "Elevated circulating von Willebrand factor in cirrhosis leads to platelet glycoprotein 1b dysfunction and platelet aggregation defects.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226965" }, { "confidence": "medium", "disease": "Chronic Liver Disease/Cirrhosis", "glycan_involvement": "Glycosylation required for receptor function and vWF binding.", "mechanism": "Defect in platelet glycoprotein 1b due to elevated vWF causes platelet dysfunction and bleeding tendency.", "protein": "platelet glycoprotein 1b", "relationship_type": "causal", "source_pmcid": "PMC12226965" }, { "confidence": "medium", "disease": "Chronic Liver Disease/Cirrhosis", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "Acquired glycoprotein VI signaling defect in cirrhosis leads to impaired platelet aggregation.", "protein": "glycoprotein VI", "protein_enriched": { "function": "Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant func", "gene_name": "GP6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9HCN6" }, "relationship_type": "causal", "source_pmcid": "PMC12226965" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (Type 2)", "glycan_involvement": "Glycosylation influences immune recognition.", "mechanism": "Cross-reactivity of antiphospholipid antibodies with beta-2 glycoprotein 1 may contribute to autoimmune liver injury.", "protein": "beta-2 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12226965" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Targets glycoprotein antigens; glycosylation affects epitope exposure.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS and associated with thrombotic risk.", "protein": "anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12226965" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation affects antigenicity.", "mechanism": "Lupus anticoagulant antibodies prolong aPTT and are associated with APS.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12226965" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (Type 2)", "glycan_involvement": "Targets microsomal glycoproteins; glycosylation may affect antigenicity.", "mechanism": "Anti-LKM antibodies are diagnostic for type 2 AIH.", "protein": "anti-LKM antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12226965" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation regulates vWF multimerization and platelet interaction.", "mechanism": "Elevated vWF in CLD contributes to platelet dysfunction and bleeding.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12226965" }, { "confidence": "low", "disease": "Intracranial Hemorrhage", "glycan_involvement": "Glycosylation affects immune complex formation.", "mechanism": "Cross-reactivity of lupus anticoagulant with beta-2 glycoprotein 1 may increase bleeding risk.", "protein": "beta-2 glycoprotein 1", "relationship_type": "causal", "source_pmcid": "PMC12226965" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation of Mac-2 binding protein is detected as M2BPGi.", "mechanism": "Serum M2BPGi levels reflect liver fibrosis severity.", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Type IV collagen is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Serum levels increase with extracellular matrix deposition in fibrosis.", "protein": "Type IV collagen 7S domain", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Hyaluronic acid is a glycosaminoglycan; its accumulation reflects ECM remodeling.", "mechanism": "Serum hyaluronic acid increases with fibrosis due to impaired clearance.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "high", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "GGT is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "Elevated GGT is common in FALD and correlates with liver congestion and fibrosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "medium", "disease": "Congestive hepatopathy", "glycan_involvement": "Glycosylation may modulate GGT activity in serum.", "mechanism": "GGT elevation is characteristic of hepatic congestion due to increased central venous pressure.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; specific glycoforms (e.g., AFP-L3) are more specific for HCC.", "mechanism": "Elevated AFP is associated with HCC development in FALD.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "Disease progression alters glycosylation pattern detected by M2BPGi assay.", "mechanism": "M2BPGi is used as a non-invasive marker for FALD progression.", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "low", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "BNP is glycosylated; glycosylation may affect its half-life.", "mechanism": "BNP is associated with cardiac dysfunction and indirectly with FALD severity.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "low", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "Glycosylation may influence detection in immunoassays.", "mechanism": "Elevated serum levels reflect ongoing fibrogenesis in FALD.", "protein": "Type IV collagen 7S domain", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "Reflects ECM glycan remodeling in liver disease.", "mechanism": "Serum hyaluronic acid is elevated in FALD and correlates with fibrosis.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12226966" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "gp130 is a glycoprotein; glycosylation is essential for receptor function and signaling.", "mechanism": "gp130 mediates IL-6/IL-6R signaling, activating JAK/STAT3 pathway, driving inflammation in UC.", "protein": "Interleukin-6 receptor subunit beta (gp130)", "relationship_type": "causal", "source_pmcid": "PMC12226995" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects stability and receptor binding.", "mechanism": "Elevated IL-6 promotes inflammation via STAT3 activation; correlates with disease severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226995" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "CRP is a glycoprotein; glycosylation modulates its immune functions.", "mechanism": "CRP is elevated in active UC; reflects systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226995" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "STAT3 is glycosylated; glycosylation may affect nuclear translocation and function.", "mechanism": "STAT3 activation drives inflammatory gene expression in UC; inhibition reduces disease severity.", "protein": "Signal transducer and activator of transcription 3 (STAT3)", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12226995" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "NF-\u03baB is glycosylated; glycosylation may regulate DNA binding and activity.", "mechanism": "NF-\u03baB activation induces pro-inflammatory cytokines, contributing to mucosal damage.", "protein": "Nuclear factor kappa B (NF-\u03baB)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12226995" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation of gp130 modulates receptor stability and oncogenic signaling.", "mechanism": "Chronic IL-6/gp130 signaling promotes tumorigenesis in UC-associated colorectal cancer.", "protein": "Interleukin-6 receptor subunit beta (gp130)", "relationship_type": "causal", "source_pmcid": "PMC12226995" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect STAT3 dimerization and nuclear import.", "mechanism": "Constitutive STAT3 activation supports tumor growth and immune evasion.", "protein": "Signal transducer and activator of transcription 3 (STAT3)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12226995" }, { "confidence": "low", "disease": "Diabetic nephropathy", "glycan_involvement": "CRP glycosylation influences renal deposition and inflammatory activity.", "mechanism": "CRP is elevated in renal inflammation; reduction reflects therapeutic response.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226995" }, { "confidence": "low", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may modulate STAT3 signaling in renal cells.", "mechanism": "STAT3 inhibition by nifuroxazide reduces renal inflammation and fibrosis.", "protein": "Signal transducer and activator of transcription 3 (STAT3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226995" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "IL-6 glycosylation affects its stability and tumor-promoting activity.", "mechanism": "Chronic IL-6 signaling promotes tumor progression in colitis-associated cancer.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12226995" }, { "confidence": "high", "disease": "Hepatic impairment", "glycan_involvement": "Altered glycosylation may affect binding properties.", "mechanism": "Albumin levels decrease in hepatic impairment, affecting drug binding and pharmacokinetics.", "protein": "Human serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12227017" }, { "confidence": "high", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation state modulates binding affinity.", "mechanism": "Levels and glycosylation of alpha-1-acid glycoprotein change in liver disease, impacting drug binding.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12227017" }, { "confidence": "high", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation affects enzyme stability and localization.", "mechanism": "Reduced CYP3A4 expression in hepatic impairment decreases drug metabolism.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "Lower CYP2C8 activity in liver disease reduces drug clearance.", "protein": "Cytochrome P450 2C8", "protein_enriched": { "function": "Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitu", "gene_name": "CYP2A6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11509" }, "relationship_type": "causal", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation impacts enzyme function.", "mechanism": "UGT1A9-mediated glucuronidation is reduced in hepatic impairment, affecting drug and metabolite elimination.", "protein": "UDP-glucuronosyltransferase 1A9", "protein_enriched": { "function": "UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, ", "gene_name": "UGT1A8", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G14669DU", "G39188ZX" ], "uniprot_id": "Q9HAW9" }, "relationship_type": "causal", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "UGT1A1 activity is decreased in liver disease, impairing glucuronidation of drug metabolites.", "protein": "UDP-glucuronosyltransferase 1A1", "relationship_type": "causal", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Chronic graft-versus-host disease (cGVHD)", "glycan_involvement": "Disease may alter glycosylation patterns.", "mechanism": "Albumin levels and glycosylation may be altered in cGVHD, affecting drug pharmacokinetics.", "protein": "Human serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Chronic graft-versus-host disease (cGVHD)", "glycan_involvement": "Disease-associated glycan changes.", "mechanism": "Changes in glycosylation and levels in cGVHD can affect drug binding and distribution.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "Glycosylation affects enzyme function.", "mechanism": "CYP3A4 metabolizes drugs like alectinib used in NSCLC; hepatic impairment alters exposure.", "protein": "Cytochrome P450 3A4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227017" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation changes are characteristic in cirrhosis.", "mechanism": "Altered glycosylation and levels in cirrhosis affect drug binding and pharmacokinetics.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12227017" }, { "confidence": "medium", "disease": "PRES", "glycan_involvement": "LDH is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated LDH is a marker of endothelial dysfunction, correlating with cerebral edema severity in PRES.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227137" }, { "confidence": "medium", "disease": "HELLP syndrome", "glycan_involvement": "Glycosylation is essential for platelet glycoprotein function and clearance.", "mechanism": "Platelet glycoprotein dysfunction contributes to thrombocytopenia in HELLP syndrome.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "Cerebral edema", "glycan_involvement": "N-glycosylation affects albumin's half-life and function.", "mechanism": "Albumin maintains oncotic pressure; hypoalbuminemia can worsen cerebral edema.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation pattern changes reflect vascular pathology.", "mechanism": "Altered transferrin glycoforms are associated with endothelial dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "Fc N-glycosylation modulates IgG effector function.", "mechanism": "Altered IgG glycosylation is linked to immune activation in preeclampsia.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "Thrombocytopenia", "glycan_involvement": "O- and N-glycosylation regulate vWF function and clearance.", "mechanism": "vWF mediates platelet adhesion; altered vWF glycosylation may contribute to platelet consumption.", "protein": "Von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "HELLP syndrome", "glycan_involvement": "N-glycosylation is essential for erythropoietin stability and activity.", "mechanism": "Erythropoietin may be used to treat anemia in HELLP syndrome.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation modulates VEGF receptor binding.", "mechanism": "VEGF mediates vascular permeability; dysregulation contributes to endothelial dysfunction.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "causal", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "HELLP syndrome", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated AST is a marker of liver injury in HELLP syndrome.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12227137" }, { "confidence": "low", "disease": "HELLP syndrome", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated ALT is a marker of liver injury in HELLP syndrome.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227137" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "SV2A is a glycoprotein; glycosylation is essential for its synaptic vesicle localization and function.", "mechanism": "Reduced SV2A availability reflects decreased synaptic density in cortical and subcortical regions, correlating with cognitive impairment.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may affect SV2A stability and synaptic function.", "mechanism": "SV2A density quantifiable by PET imaging may serve as a target for monitoring neuroprotective or remyelination therapies.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "SV2A glycosylation status not specified but implied as functionally relevant.", "mechanism": "10\u201315% reduction in SV2A availability in cortical areas and hippocampus reflects synaptic loss.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "SV2A glycosylation status not specified but implied as functionally relevant.", "mechanism": "15% reduction in SV2A in prefrontal cortex, anterior cingulate, and hippocampus indicates synaptic loss.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Alzheimer Disease", "glycan_involvement": "SV2A glycosylation status not specified but implied as functionally relevant.", "mechanism": "Over 40% reduction in SV2A in hippocampus reflects severe synaptic loss.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Parkinson Disease", "glycan_involvement": "SV2A glycosylation status not specified but implied as functionally relevant.", "mechanism": "Up to 35% reduction in SV2A in substantia nigra reflects synaptic loss.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "medium", "disease": "Cannabis Use Disorder", "glycan_involvement": "SV2A glycosylation status not specified but implied as functionally relevant.", "mechanism": "Approximately 10% synaptic loss in hippocampus measured by SV2A PET imaging.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation of SV2A is necessary for synaptic vesicle function, impacting synaptic density.", "mechanism": "Reduced SV2A availability is directly involved in cognitive dysfunction and progression of cognitive disability.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "causal", "source_pmcid": "PMC12227148" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "SV2A glycosylation is required for its synaptic localization and function.", "mechanism": "SV2A PET imaging enables in vivo quantification of synaptic loss, which is not always associated with brain atrophy.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "SV2A glycosylation is essential for its role in synaptic transmission.", "mechanism": "SV2A reduction in temporal, insular, occipital, cingulate, frontal, and parietal cortices correlates with impaired information processing speed.", "protein": "Synaptic Vesicle Glycoprotein 2A (SV2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12227148" }, { "confidence": "high", "disease": "Leaf blight of Panax vietnamensis", "glycan_involvement": "PvCOMT2 is involved in lignin (a phenolic polymer, not a glycan) biosynthesis; no direct evidence of glycosylation.", "mechanism": "PvCOMT2 promotes lignin biosynthesis, strengthening cell walls and enhancing resistance to Neofusicoccum ribis.", "protein": "PvCOMT2", "relationship_type": "protective", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Leaf blight of Panax vietnamensis", "glycan_involvement": "No direct glycosylation involvement; acts as a transcriptional repressor.", "mechanism": "PvWRKY40 represses PvCOMT2 expression, reducing lignin biosynthesis and increasing susceptibility to N. ribis.", "protein": "PvWRKY40", "relationship_type": "causal (negative regulator)", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Fusarium oxysporum infection", "glycan_involvement": "No direct evidence of glycosylation; function is via lignin biosynthesis.", "mechanism": "Overexpression of PvCOMT2 in Nicotiana benthamiana increases lignin content and confers resistance to F. oxysporum.", "protein": "PvCOMT2", "relationship_type": "protective", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Fusarium oxysporum infection", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Overexpression of PvWRKY40 in N. benthamiana suppresses lignin and increases susceptibility to F. oxysporum.", "protein": "PvWRKY40", "relationship_type": "causal (negative regulator)", "source_pmcid": "PMC12227329" }, { "confidence": "medium", "disease": "Leaf blight of Panax vietnamensis", "glycan_involvement": "No direct evidence of glycosylation; acts in lignin pathway.", "mechanism": "PvCOMT1 is upregulated by melatonin and contributes to lignin biosynthesis, enhancing disease resistance.", "protein": "PvCOMT1", "relationship_type": "protective", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Leaf blight of Panax vietnamensis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Melatonin suppresses PvWRKY40, relieving repression of PvCOMT2 and promoting lignin-mediated defence.", "protein": "PvWRKY40", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Leaf blight of Panax vietnamensis", "glycan_involvement": "No direct evidence of glycosylation.", "mechanism": "PvCOMT2 overexpression or melatonin treatment enhances lignin biosynthesis and resistance.", "protein": "PvCOMT2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227329" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma (MTC)", "glycan_involvement": "Calcitonin is glycosylated, which may affect its stability and secretion.", "mechanism": "Produced and secreted by C-cells; elevated serum levels indicate presence and progression of MTC.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma (MTC)", "glycan_involvement": "CEA is heavily glycosylated; glycosylation is essential for its secretion and immunogenicity.", "mechanism": "CEA is secreted by MTC cells; elevated serum levels correlate with tumor burden and progression.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Cervical lymph node metastasis", "glycan_involvement": "Glycosylation may influence calcitonin's serum half-life and detection.", "mechanism": "Basal serum calcitonin levels above specific thresholds predict lymph node metastasis.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "Glycosylation may affect calcitonin's stability and detection in serum.", "mechanism": "Serum calcitonin >500 pg/mL is indicative of distant metastasis, including lung.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "medium", "disease": "Lung metastasis", "glycan_involvement": "Glycosylation is critical for CEA's function as a serum biomarker.", "mechanism": "Elevated CEA levels may indicate metastatic spread to the lung.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "medium", "disease": "Cervical lymph node metastasis", "glycan_involvement": "Glycosylation affects CEA's immunoreactivity and detection.", "mechanism": "CEA levels correlate with extent of lymph node involvement in MTC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma (MTC)", "glycan_involvement": "Glycosylation may affect calcitonin clearance post-surgery.", "mechanism": "Postoperative normalization of calcitonin indicates successful surgical treatment.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma (MTC)", "glycan_involvement": "Glycosylation impacts CEA's serum levels and clearance.", "mechanism": "Postoperative normalization of CEA indicates successful surgical treatment.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227394" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation is essential for CEA's biomarker function.", "mechanism": "CEA is also used as a biomarker in NSCLC, though less specific than in MTC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation does not impact NSCLC diagnosis via calcitonin.", "mechanism": "Calcitonin is not a biomarker for NSCLC; elevated levels suggest MTC origin.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227394" }, { "confidence": "high", "disease": "Barth Syndrome", "glycan_involvement": "PGP is a glycoprotein intermediate in CL biosynthesis.", "mechanism": "PGP is a precursor in cardiolipin biosynthesis; defects in its pathway contribute to MLCL accumulation and mitochondrial dysfunction in Barth Syndrome.", "protein": "p-glycoprotein (PGP)", "relationship_type": "causal", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "Glycosylation may affect Mfn2 stability and function.", "mechanism": "Mfn2 overexpression promotes mitochondrial fusion and autophagosome formation, increasing cell viability and neuroprotection after I/R injury.", "protein": "Mitofusin 2 (Mfn2)", "relationship_type": "protective", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "Glycosylation status may regulate Opa1 isoform balance.", "mechanism": "L-Opa1 overexpression rescues mitochondrial morphology and cell viability; excessive S-Opa1 accumulation leads to fragmentation and cell death.", "protein": "Optic atrophy 1 (Opa1)", "protein_enriched": { "function": "Plays a role in mitochondrial and peroxisomal fission (PubMed:18353969, PubMed:23530241, PubMed:24196833). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (D", "gene_name": "MFF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9GZY8" }, "relationship_type": "protective", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Drp1-mediated fission is upregulated after I/R, causing mitochondrial fragmentation and cell death; inhibition is neuroprotective.", "protein": "Dynamin-related protein 1 (Drp1)", "protein_enriched": { "function": "Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:1941", "gene_name": "DNM1L", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00429" }, "relationship_type": "causal", "source_pmcid": "PMC12227610" }, { "confidence": "medium", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "Potential glycosylation affects isoform stability.", "mechanism": "Altered MCL-1 isoform ratio affects mitochondrial morphology and increases autophagy, impacting cell survival after I/R.", "protein": "Myeloid cell leukemia factor-1 (MCL-1)", "protein_enriched": { "function": "Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of ap", "gene_name": "MCL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07820" }, "relationship_type": "causal", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "PINK1 overexpression reduces cell death and infarct volume by promoting mitophagy and mitochondrial clearance.", "protein": "PTEN-induced kinase 1 (PINK1)", "protein_enriched": { "function": "Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordi", "gene_name": "PINK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXM7" }, "relationship_type": "protective", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Ischemia/Reperfusion (I/R) Injury", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Parkin-mediated mitophagy degrades damaged mitochondria, reducing Drp1-induced fragmentation and improving outcomes.", "protein": "Parkin", "protein_enriched": { "function": "Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed", "gene_name": "PRKN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60260" }, "relationship_type": "protective", "source_pmcid": "PMC12227610" }, { "confidence": "medium", "disease": "Acute Lung Injury", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "PINK1 binds and degrades CRLS1, reducing CL synthesis, leading to mitochondrial dysfunction and increased cell death in acute lung injury.", "protein": "Cardiolipin synthase 1 (CRLS1)", "protein_enriched": { "function": "UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in prote", "gene_name": "DPAGT1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9H3H5" }, "relationship_type": "causal", "source_pmcid": "PMC12227610" }, { "confidence": "medium", "disease": "Type II Diabetes", "glycan_involvement": "Cardiolipin is a phospholipid, not a glycoprotein.", "mechanism": "Oxidized cardiolipin is detected in plasma early in Type II diabetes, indicating mitochondrial dysfunction.", "protein": "Cardiolipin", "relationship_type": "biomarker", "source_pmcid": "PMC12227610" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Cardiolipin is a phospholipid, not a glycoprotein.", "mechanism": "Altered cardiolipin profiles are observed in Alzheimer's Disease, reflecting mitochondrial dysfunction.", "protein": "Cardiolipin", "relationship_type": "biomarker", "source_pmcid": "PMC12227610" }, { "confidence": "high", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "O-glycosylation critical for barrier function; desialylation increases susceptibility.", "mechanism": "Degradation of O-glycosylated Muc2 leads to loss of mucus barrier and increased mucosal damage after irradiation.", "protein": "Mucin-2 (Muc2)", "protein_enriched": { "function": "Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth when prov", "gene_name": "Tnc", "glycan_count": 13, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G02815KT", "G06110VR", "G66538GV", "G45504EY", "G23719VF", "G39471UU", "G77547TA", "G90039BC", "G41247ZX", "G86182NS", "G14972EH", "G74724QE", "G49108TO" ], "uniprot_id": "Q80YX1" }, "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "high", "disease": "Chronic mucosal inflammation", "glycan_involvement": "O-glycan degradation and desialylation facilitate bacterial access.", "mechanism": "Loss of glycosylated Muc2 allows bacterial invasion, triggering inflammation.", "protein": "Mucin-2 (Muc2)", "protein_enriched": { "function": "Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth when prov", "gene_name": "Tnc", "glycan_count": 13, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G02815KT", "G06110VR", "G66538GV", "G45504EY", "G23719VF", "G39471UU", "G77547TA", "G90039BC", "G41247ZX", "G86182NS", "G14972EH", "G74724QE", "G49108TO" ], "uniprot_id": "Q80YX1" }, "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "SCFA-induced recruitment, not direct glycosylation effect.", "mechanism": "Oat bran fiber increases SCFA production, which recruits neutrophils and enhances elastase-mediated antimicrobial defense.", "protein": "Neutrophil elastase", "protein_enriched": { "function": "Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of", "gene_name": "ELANE", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G93279DZ", "G00395TQ", "G08290VR", "G11870QZ", "G27058EU", "G28681TP", "G29299MO", "G47644PP", "G47950XN", "G61334IA", "G82348BZ", "G00912UN", "G11314AS", "G25637MV", "G36379GD", "G59626AS", "G72291OX", "G95865ZB" ], "uniprot_id": "P08246" }, "relationship_type": "protective", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Fermentation of dietary fiber to SCFAs, supporting glycoprotein barrier.", "mechanism": "Roseburia abundance (butyrate producer) is reduced in colorectal cancer and after irradiation; its presence supports mucosal health.", "protein": "Roseburia spp.", "relationship_type": "protective", "source_pmcid": "PMC12227613" }, { "confidence": "high", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "Degrades O-glycans on Muc2.", "mechanism": "Expansion of Akkermansia in fiber-deprived/irradiated mice increases mucus degradation and barrier erosion.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Gut dysbiosis", "glycan_involvement": "Desialylation of Muc2 O-glycans.", "mechanism": "Expansion in fiber-deprived/irradiated mice increases sialic acid catabolism and mucus barrier breakdown.", "protein": "Escherichia spp.", "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Gut dysbiosis", "glycan_involvement": "Desialylation of Muc2 O-glycans.", "mechanism": "Expansion in fiber-deprived mice increases sialic acid catabolism and mucus degradation.", "protein": "Lactobacillus spp.", "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "Fermentation of fiber to SCFAs, supporting glycoprotein barrier.", "mechanism": "Higher abundance in oat bran-fed mice increases butyrate production, supporting mucosal integrity.", "protein": "Ruminococcaceae UCG-009", "relationship_type": "protective", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "Associated with dysbiosis and altered glycoprotein environment.", "mechanism": "Higher abundance in fiber-deprived/irradiated mice is linked to increased tissue damage.", "protein": "Erysipelatoclostridium", "relationship_type": "biomarker", "source_pmcid": "PMC12227613" }, { "confidence": "medium", "disease": "Radiation-induced intestinal injury", "glycan_involvement": "Associated with increased mucus degradation.", "mechanism": "Expansion in fiber-deprived/irradiated mice is associated with harmful effects and increased mucosal damage.", "protein": "Parabacteroides spp.", "relationship_type": "causal", "source_pmcid": "PMC12227613" }, { "confidence": "high", "disease": "POEMS syndrome", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Elevated serum VEGF is a key diagnostic marker; promotes angiogenesis and vascular permeability.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "medium", "disease": "Vasculitic neuropathy", "glycan_involvement": "VEGF glycosylation may influence its release and activity.", "mechanism": "Serum VEGF can be elevated due to inflammation and platelet activation at vasculitic sites.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "medium", "disease": "Iron-deficiency anemia", "glycan_involvement": "Glycosylation modulates VEGF secretion.", "mechanism": "Tissue hypoxia from anemia induces VEGF via HIF-1\u03b1 activation.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect VEGF's inflammatory signaling.", "mechanism": "VEGF correlates with disease activity and synovial neovascularization.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12228050" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may regulate VEGF-A release.", "mechanism": "Serum VEGF-A elevated due to platelet aggregation at vasculitic sites.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "low", "disease": "Chronic inflammatory demyelinating polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation may affect VEGF function.", "mechanism": "VEGF levels can be increased in CIDP, reflecting inflammation.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "low", "disease": "Myelin-associated glycoprotein-positive neuropathy", "glycan_involvement": "Glycosylation may influence VEGF's role.", "mechanism": "VEGF can be elevated in this neuropathy subtype.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "high", "disease": "Myelin-associated glycoprotein-positive neuropathy", "glycan_involvement": "MAG is a glycoprotein; glycosylation is essential for its function and antigenicity.", "mechanism": "Autoantibodies against MAG cause demyelinating neuropathy.", "protein": "Myelin-Associated Glycoprotein (MAG)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "medium", "disease": "POEMS syndrome", "glycan_involvement": "IgG is glycosylated; glycosylation affects immune function.", "mechanism": "Monoclonal gammopathy is a diagnostic criterion for POEMS.", "protein": "Immunoglobulin G kappa-type M protein", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "low", "disease": "Vasculitic neuropathy", "glycan_involvement": "Autoantibodies are glycoproteins; glycosylation modulates immune response.", "mechanism": "Presence may indicate autoimmune involvement, though not causative in this case.", "protein": "Anti-Sj\u00f6gren\u2019s syndrome-B (SS-B) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12228050" }, { "confidence": "high", "disease": "Cervical cancer (squamous cell carcinoma of the cervix)", "glycan_involvement": "Glycosylation is essential for SCCA secretion and stability as a serum biomarker.", "mechanism": "SCCA is produced by squamous epithelial cells and is elevated in serum of women with cervical cancer; used for diagnosis, monitoring, and prognosis.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Pulmonary tuberculosis", "glycan_involvement": "Glycosylation enables SCCA secretion into serum in non-malignant squamous cell activation.", "mechanism": "SCCA can be elevated in benign inflammatory conditions, leading to reduced specificity.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Bronchogenic cyst", "glycan_involvement": "Glycosylation supports SCCA stability in circulation.", "mechanism": "Elevated SCCA observed in some benign cystic lesions.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Eczema", "glycan_involvement": "Glycosylation allows SCCA to be secreted during squamous cell activation.", "mechanism": "SCCA can be elevated in inflammatory skin diseases.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Pemphigus", "glycan_involvement": "Glycosylation facilitates SCCA release from affected squamous cells.", "mechanism": "SCCA may be elevated in autoimmune skin diseases.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation is required for SCCA secretion from hyperproliferative squamous cells.", "mechanism": "SCCA can be elevated in chronic inflammatory skin conditions.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Cervical cancer (squamous cell carcinoma of the cervix)", "glycan_involvement": "Glycosylation may affect SCCA's immunogenicity and clearance.", "mechanism": "SCCA is being explored for its role in monitoring response to therapy and recurrence.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target (potential)", "source_pmcid": "PMC12228214" }, { "confidence": "medium", "disease": "Cervical cancer (squamous cell carcinoma of the cervix)", "glycan_involvement": "Glycosylation status may influence SCCA detectability but not disease extent correlation.", "mechanism": "SCCA levels do not significantly correlate with disease stage, lymph node involvement, or parametrial invasion in this population.", "protein": "Squamous cell carcinoma antigen (SCCA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12228214" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "sCD25 is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Elevated sCD25 reflects T-cell activation and is a diagnostic marker for HLH.", "protein": "Soluble interleukin-2 receptor (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is glycosylated, which affects its serum stability.", "mechanism": "Hyperferritinemia is a hallmark of HLH due to macrophage activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "EBV envelope glycoproteins mediate host cell entry via glycan recognition.", "mechanism": "EBV infection/reactivation can trigger HLH, especially in lymphoma patients.", "protein": "Epstein-Barr virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12228357" }, { "confidence": "high", "disease": "Hodgkin's lymphoma", "glycan_involvement": "CD30 is a glycoprotein; glycosylation affects ligand binding and antibody recognition.", "mechanism": "CD30 is highly expressed on Hodgkin/Reed-Sternberg cells and targeted by brentuximab vedotin.", "protein": "CD30 (TNFRSF8)", "protein_enriched": { "function": "Receptor for TNFSF8/CD30L (PubMed:8391931). May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-", "gene_name": "TNFRSF8", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P28908" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12228357" }, { "confidence": "medium", "disease": "Hodgkin's lymphoma", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated sCD25 can indicate immune activation in Hodgkin's lymphoma.", "protein": "Soluble interleukin-2 receptor (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "medium", "disease": "Hodgkin's lymphoma", "glycan_involvement": "Viral glycoproteins interact with host glycans for infection.", "mechanism": "EBV infection is associated with a subset of Hodgkin's lymphoma cases.", "protein": "Epstein-Barr virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12228357" }, { "confidence": "low", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Transferrin is N-glycosylated, affecting serum half-life.", "mechanism": "Transferrin levels may be altered in HLH due to iron metabolism dysregulation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "low", "disease": "Hodgkin's lymphoma", "glycan_involvement": "Glycosylation affects ferritin secretion.", "mechanism": "Ferritin may be elevated in Hodgkin's lymphoma due to inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "low", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Elevated sCD25 may reflect immune activation in DILI, but is not specific.", "protein": "Soluble interleukin-2 receptor (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "low", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "CD30+ T cells may be involved in HLH pathogenesis in lymphoma.", "protein": "CD30 (TNFRSF8)", "protein_enriched": { "function": "Receptor for TNFSF8/CD30L (PubMed:8391931). May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-", "gene_name": "TNFRSF8", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P28908" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228357" }, { "confidence": "high", "disease": "Liver abscess", "glycan_involvement": "Capsular polysaccharide is a glycan-rich structure critical for pathogenicity.", "mechanism": "K1/K2 capsular glycoproteins confer hypermucoviscosity, immune evasion, and increased virulence, leading to abscess formation.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation of capsule increases resistance to phagocytosis.", "mechanism": "Hypervirulent strains disseminate hematogenously due to capsular glycoprotein-mediated immune evasion.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "medium", "disease": "Endocarditis", "glycan_involvement": "Glycan-rich capsule protects against host defenses.", "mechanism": "Capsular glycoproteins facilitate bacterial survival in bloodstream, leading to endocardial infection.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "medium", "disease": "Epidural abscess", "glycan_involvement": "Hypermucoid capsule aids tissue invasion.", "mechanism": "Capsular glycoproteins enable metastatic spread to epidural space.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "high", "disease": "Liver abscess", "glycan_involvement": "Regulates glycoprotein capsule expression.", "mechanism": "rmpA upregulates capsule synthesis, increasing virulence and abscess formation.", "protein": "rmpA protein", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "high", "disease": "Liver abscess", "glycan_involvement": "Involved in glycoprotein capsule biosynthesis.", "mechanism": "magA is associated with hypermucoviscosity and capsule formation, promoting abscess development.", "protein": "magA protein", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "medium", "disease": "Cerebral septic emboli", "glycan_involvement": "Glycosylation enhances resistance to immune clearance.", "mechanism": "Capsular glycoproteins facilitate survival in circulation, leading to embolic spread to the brain.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "medium", "disease": "Osteomyelitis", "glycan_involvement": "Glycan-rich capsule aids in tissue invasion.", "mechanism": "Capsular glycoproteins promote hematogenous dissemination to bone.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal", "source_pmcid": "PMC12228582" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein whose glycosylation affects its function.", "mechanism": "CRP is elevated in systemic infection and used to monitor inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228582" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Host hyperglycemia may enhance bacterial glycan synthesis.", "mechanism": "Diabetes impairs immune response, increasing susceptibility to glycoprotein-mediated HVKP infection.", "protein": "Klebsiella pneumoniae capsular polysaccharide (K1/K2)", "relationship_type": "causal (risk factor interaction)", "source_pmcid": "PMC12228582" }, { "confidence": "high", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Beta2-glycoprotein I is heavily glycosylated; glycan structures may influence antigenicity and antibody binding.", "mechanism": "Presence of anti-beta2-glycoprotein I IgG antibodies is associated with increased risk of early-onset CIS, likely via prothrombotic effects.", "protein": "beta2-glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Antigenic targets may include glycosylated proteins/lipids; glycosylation may affect immune recognition.", "mechanism": "Medium/high titers of anticardiolipin IgG antibodies are associated with increased risk of early-onset CIS, likely via endothelial and platelet activation.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Not directly discussed.", "mechanism": "No significant association found between lupus anticoagulant and early-onset CIS in this cohort.", "protein": "lupus anticoagulant", "relationship_type": "no association", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of beta2-glycoprotein I may modulate immune response and antibody binding.", "mechanism": "Anti-beta2-glycoprotein I antibodies are diagnostic and pathogenic in APS, contributing to thrombosis.", "protein": "beta2-glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycan structures on target proteins/lipids may affect antibody binding.", "mechanism": "Anticardiolipin IgG antibodies are diagnostic and pathogenic in APS, promoting thrombosis.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228635" }, { "confidence": "medium", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Estrogen use in anti-beta2-glycoprotein I positive individuals further increases CIS risk.", "protein": "beta2-glycoprotein I", "relationship_type": "risk potentiation", "source_pmcid": "PMC12228635" }, { "confidence": "medium", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Possible involvement in antibody consumption/localization at thrombotic sites.", "mechanism": "Frequency of anti-beta2-glycoprotein I antibodies increases from acute phase to 12 weeks post-stroke, suggesting dynamic biomarker utility.", "protein": "beta2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12228635" }, { "confidence": "medium", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Possible involvement in antibody consumption/localization at thrombotic sites.", "mechanism": "Frequency of anticardiolipin IgG antibodies increases from acute phase to 12 weeks post-stroke.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12228635" }, { "confidence": "medium", "disease": "cryptogenic ischemic stroke (CIS)", "glycan_involvement": "Not discussed.", "mechanism": "No difference in high-risk patent foramen ovale (PFO) frequency between anti-beta2-glycoprotein I positive and negative patients.", "protein": "beta2-glycoprotein I", "relationship_type": "no association", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Not discussed.", "mechanism": "Lupus anticoagulant is a diagnostic marker for APS and associated with thrombosis in APS, but not with CIS in this study.", "protein": "lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228635" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Reduces hepatic steatosis, insulin resistance, and inflammation by inhibiting fat synthesis and promoting lipolysis and \u03b2-oxidation.", "protein": "Zinc-\u03b12-glycoprotein (ZAG)", "protein_enriched": { "function": "Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids", "gene_name": "AZGP1", "glycan_count": 201, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G01485JJ", "G02628JF", "G02815KT", "G04854VP", "G05049YU", "G06247RL", "G06356OH", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G14260UH", "G14972EH", "G15169WU", "G17208MA", "G20312EM", "G20706XG", "G22310AV", "G23719VF", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27947YN", "G28681TP", "G31852PQ", "G33416PL", "G33791AF", "G35029YA", "G36379GD", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42962KI", "G43223CG", "G43669FQ", "G43734MM", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46524LG", "G46687AB", "G46902YN", "G47448YK", "G47518TP", "G47644PP", "G48414YA", "G50045TK", "G50427EO", "G51413EV", "G52527GH", "G54010QB", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64162JC", "G64527OM", "G66163OV", "G70101JE", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G72787SB", "G72791KH", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G79286RS", "G80333GO", "G81198YO", "G82463GQ", "G83229XP", "G84452RH", "G85144OK", "G85269DF", "G86234IN", "G86795LJ", "G88374WZ", "G88891KO", "G90575OW", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95865ZB", "G98129XB", "G00395TQ", "G23863VK", "G31685JQ", "G31916IQ", "G42358LZ", "G47737VJ", "G57818FI", "G70894RY", "G74724QE", "G77582RK", "G82348BZ", "G96577RX", "G02030ZB", "G03382KH", "G03930BU", "G05724UK", "G05933EN", "G06110VR", "G07246CJ", "G07755XJ", "G10256JP", "G10773YW", "G10819WX", "G11870QZ", "G12313PD", "G12579WK", "G14994KB", "G16175ZV", "G18647XP", "G20210JR", "G22572EH", "G22625SJ", "G23294PN", "G25418HZ", "G27126ED", "G29880MM", "G31544HA", "G34617SM", "G40664HB", "G41071NU", "G42124LM", "G46691LC", "G47012YE", "G49874UX", "G51640FO", "G54612UD", "G55383ZG", "G60177UT", "G60923RB", "G62894KT", "G63381RX", "G64409MC", "G65019XG", "G65184UU", "G66760KM", "G70418MS", "G70822IO", "G72735IY", "G72797UR", "G74430RZ", "G78790NZ", "G80223IX", "G80920RR", "G81263BG", "G82020ZR", "G82119TF", "G82830MN", "G83460ZZ", "G83646BJ", "G84820NF", "G86182NS", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G90093AU", "G91473PK", "G92062TF", "G94854LT", "G95133RI", "G95977AE", "G96091TT", "G98611JV", "G39213VZ", "G90725ZC", "G96957PS", "G49108TO" ], "uniprot_id": "P25311" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12232929" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects membrane localization and function.", "mechanism": "Promotes hepatic fatty acid uptake and lipid accumulation; palmitoylation status modulates activity.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12232929" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects stability and serum half-life.", "mechanism": "Low SHBG levels are associated with increased hepatic lipogenesis and NAFLD risk.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12232929" }, { "confidence": "medium", "disease": "Acute liver failure (ALF)", "glycan_involvement": "Glycosylation required for secretion and immune modulation.", "mechanism": "Upregulated in macrophages during liver injury; higher levels correlate with poorer prognosis.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12232929" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Mediates HDL/LDL uptake; endothelial SR-BI promotes LDL uptake and atherogenesis.", "protein": "SR-BI (Scavenger receptor class B type I)", "protein_enriched": { "function": "Receptor for different ligands such as phospholipids, cholesterol ester, lipoproteins, phosphatidylserine and apoptotic cells (PubMed:12016218, PubMed:12519372, PubMed:21226579). Receptor for HDL, med", "gene_name": "SCARB1", "glycan_count": 12, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G92942VI", "G71125PP", "G05962QB", "G11101UV", "G40834TG", "G69521XL", "G63332OE", "G64527OM", "G37399XV", "G54010QB", "G57321FI", "G49108TO" ], "uniprot_id": "Q8WTV0" }, "relationship_type": "causal", "source_pmcid": "PMC12232929" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for ECM interactions.", "mechanism": "Regulates hepatic stellate cell activation and fibrosis; deficiency prevents NASH phenotypes.", "protein": "Thrombospondin-1 (TSP-1)", "protein_enriched": { "function": "Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:15014436, PubMed:18285447, PubMed:2430973, PubMed:6489349). Multifunctional, involved in inflammation, angiogen", "gene_name": "THBS1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G37881RL", "G52527GH", "G56784JY", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G06110VR", "G06356OH", "G07755XJ", "G08290VR", "G08918WF", "G09197ZW", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G12313PD", "G14260UH", "G14669DU", "G14994KB", "G15664MX", "G16175ZV", "G18647XP", "G20210JR", "G20425TQ", "G22140GZ", "G22310AV", "G23432EQ", "G23453IV", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31852PQ", "G31916IQ", "G31936TA", "G32332VU", "G33609NS", "G34989PA", "G35029YA", "G37399XV", "G37412TK", "G37509XX", "G37868ZX", "G39446WN", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46687AB", "G46691LC", "G46902YN", "G47644PP", "G48414YA", "G48584BU", "G49906RN", "G49955PK", "G50045TK", "G50757KG", "G51640FO", "G54612UD", "G55383ZG", "G57317CE", "G57776ZU", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G61256FT", "G62765YT", "G64527OM", "G65092SV", "G65184UU", "G66621EA", "G66766XF", "G70101JE", "G70418MS", "G70441OD", "G70619PT", "G72291OX", "G72398FA", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G75983OB", "G76295SF", "G78790NZ", "G79568CQ", "G80223IX", "G80920RR", "G81263BG", "G81295CK", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84820NF", "G85554PZ", "G86182NS", "G87399DK", "G87661QW", "G89098OM", "G90659AW", "G90734RJ", "G91636VS", "G92050GC", "G92406TI", "G95046LV", "G95865ZB", "G49108TO", "G00273SJ", "G02528FI", "G07246CJ", "G08110WX", "G10846ZT", "G11629QQ", "G14972EH", "G17208MA", "G20706XG", "G28622IK", "G37818NZ", "G40834TG", "G43669FQ", "G43734MM", "G57776ZS", "G59324HL", "G60834IK", "G64409MC", "G65000LJ", "G70223PD", "G70232NH", "G72667IM", "G73430PD", "G77547TA", "G79666IR", "G80479JV", "G81198YO", "G84225JN", "G85282JO", "G86880BF", "G87123QX", "G90382BL", "G90575OW", "G92135MA", "G92551JA", "G93718GY", "G95977AE", "G98611JV", "G99966GV", "G57321FI", "G02030ZB", "G05724UK", "G08146BT", "G10256JP", "G11870QZ", "G12341GU", "G13910DJ", "G20528HD", "G22625SJ", "G23294PN", "G29299MO", "G29880MM", "G33584ML", "G39188ZX", "G39619TI", "G47012YE", "G47950XN", "G49874UX", "G60177UT", "G63041LO", "G63381RX", "G70375MX", "G72797UR", "G74430RZ", "G80075MS", "G85269DF", "G87051GH", "G95177YH", "G96577RX", "G61491DK", "G06038KF", "G42494UJ", "G96881BQ", "G42518JM", "G81399MY", "G29068FM", "G70323CJ" ], "uniprot_id": "P07996" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12232929" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated serum levels distinguish HCC from cirrhosis; superior to AFP.", "protein": "Lipocalin-2 (LCN-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12232929" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Specific glycosylation isomer detected as marker.", "mechanism": "Elevated in cirrhosis and HCC; predicts progression in HBV/HCV patients.", "protein": "Human Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC12232929" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Promotes insulin resistance and hepatic steatosis; downregulation improves metabolic parameters.", "protein": "\u03b1-2-HS glycoprotein (AHSG, fetuin-A)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12232929" }, { "confidence": "medium", "disease": "NASH (Non-alcoholic steatohepatitis)", "glycan_involvement": "N-glycosylation of SCAP exacerbates disease.", "mechanism": "Aberrant N-glycosylation enhances lipid accumulation and inflammation via epigenetic modification.", "protein": "SREBP cleavage-activating protein (SCAP)", "protein_enriched": { "function": "Escort protein required for cholesterol as well as lipid homeostasis (By similarity). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, there", "gene_name": "SCAP", "glycan_count": 7, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G31852PQ", "G41247ZX", "G62765YT", "G28465XX", "G57321FI", "G49108TO" ], "uniprot_id": "Q12770" }, "relationship_type": "causal", "source_pmcid": "PMC12232929" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DGC includes glycoproteins; dystrophin links cytoskeleton to glycosylated membrane proteins.", "mechanism": "Null mutations in DMD gene cause loss of dystrophin, destabilizing the DGC and leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct evidence of glycosylation for DWORF; effect is via regulation of SERCA2a.", "mechanism": "DWORF expression is significantly reduced in skeletal and cardiac muscle of DMD-affected dogs; loss may contribute to impaired calcium handling and muscle function.", "protein": "DWORF (Dwarf Open Reading Frame)", "protein_enriched": { "function": "Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988, PubM", "gene_name": "SMDT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4I9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Cardiomyopathy (in DMD context)", "glycan_involvement": "No direct evidence of glycosylation for DWORF.", "mechanism": "DWORF overexpression restores SERCA function and mitigates heart disease in DMD mouse models.", "protein": "DWORF (Dwarf Open Reading Frame)", "protein_enriched": { "function": "Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988, PubM", "gene_name": "SMDT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4I9" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12233064" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "No direct evidence of glycosylation for DWORF.", "mechanism": "Reduced DWORF expression observed in human heart failure and animal models; DWORF enhances SERCA2a activity.", "protein": "DWORF (Dwarf Open Reading Frame)", "protein_enriched": { "function": "Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988, PubM", "gene_name": "SMDT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4I9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct evidence of glycosylation discussed for SERCA2a in this article.", "mechanism": "SERCA2a activity is reduced in DMD; enhancing its function (e.g., via DWORF) improves calcium handling and muscle function.", "protein": "SERCA2a (ATP2A2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Cardiomyopathy (in DMD context)", "glycan_involvement": "DGC includes glycoproteins; loss disrupts glycoprotein-mediated membrane stability.", "mechanism": "Dystrophin deficiency leads to membrane instability, calcium overload, and cardiomyocyte death.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12233064" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "DGC disruption affects glycoprotein interactions at the membrane.", "mechanism": "Loss of dystrophin in heart leads to progressive fibrosis and pump failure.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct evidence of glycosylation for DWORF.", "mechanism": "Progressive decline of DWORF expression in muscle correlates with disease severity and age in DMD dogs.", "protein": "DWORF (Dwarf Open Reading Frame)", "protein_enriched": { "function": "Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988, PubM", "gene_name": "SMDT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4I9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct evidence of glycosylation for DWORF.", "mechanism": "AAV-mediated DWORF overexpression ameliorates DMD cardiomyopathy in mouse models.", "protein": "DWORF (Dwarf Open Reading Frame)", "protein_enriched": { "function": "Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988, PubM", "gene_name": "SMDT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4I9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12233064" }, { "confidence": "medium", "disease": "Cardiomyopathy (in DMD context)", "glycan_involvement": "No direct evidence of glycosylation discussed for SERCA2a in this article.", "mechanism": "SERCA2a activation (by DWORF or other means) improves cardiac function in DMD models.", "protein": "SERCA2a (ATP2A2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12233064" }, { "confidence": "high", "disease": "Enterovirus B infection (e.g., Echovirus, Coxsackievirus B)", "glycan_involvement": "FcRn glycosylation stabilizes receptor structure and ligand binding.", "mechanism": "FcRn acts as an uncoating receptor, facilitating viral genome release in acidic endosomes.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRSV)", "glycan_involvement": "FcRn glycosylation required for proper folding and receptor function.", "mechanism": "FcRn mediates endosomal uncoating of PRRSV via interaction with viral N and M glycoproteins.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Human astrovirus infection", "glycan_involvement": "FcRn glycosylation supports spike protein binding and receptor stability.", "mechanism": "FcRn serves as a primary entry receptor for human astrovirus via direct binding to viral spike protein.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "FcRn glycosylation maintains receptor conformation for IgG binding.", "mechanism": "FcRn mediates transcytosis of IgG-HIV-1 complexes across genital epithelium, facilitating mucosal transmission.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Zika virus infection (vertical transmission)", "glycan_involvement": "FcRn glycosylation essential for placental transport function.", "mechanism": "FcRn transports IgG-ZIKV complexes across placental barrier, enabling fetal infection via ADE.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Human cytomegalovirus (CMV) infection (congenital)", "glycan_involvement": "FcRn glycosylation required for IgG binding and transcytosis.", "mechanism": "FcRn mediates transcytosis of IgG-CMV complexes across placental barrier, influencing congenital infection risk.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "causal", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Influenza virus infection", "glycan_involvement": "FcRn glycosylation supports IgG binding and endosomal trafficking.", "mechanism": "FcRn enables intracellular neutralization by transporting IgG into endosomes, blocking viral uncoating.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "protective", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Autoimmune diseases (e.g., myasthenia gravis)", "glycan_involvement": "FcRn glycosylation affects IgG binding and therapeutic targeting.", "mechanism": "FcRn inhibition accelerates clearance of pathogenic IgG, reducing autoimmune symptoms.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12233286" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "FcRn glycosylation required for IgG transport.", "mechanism": "FcRn-mediated IgG transcytosis supports mucosal immunity and vaccine efficacy.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "protective", "source_pmcid": "PMC12233286" }, { "confidence": "medium", "disease": "Porcine epidemic diarrhea virus (PEDV) infection", "glycan_involvement": "FcRn glycosylation supports antigen transport.", "mechanism": "FcRn-based vaccine strategies enhance mucosal immunity against PEDV.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "protective", "source_pmcid": "PMC12233286" }, { "confidence": "high", "disease": "Rice blast", "glycan_involvement": "N-glycosylation required for effector function and immune evasion.", "mechanism": "Suppresses host ROS production and evades innate immunity via N-glycosylation.", "protein": "Slp1", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Verticillium wilt", "glycan_involvement": "N-glycosylation enables immune evasion.", "mechanism": "Suppresses host cell death and immune response; N-glycosylation essential for immune suppression.", "protein": "VdSCP23", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Phytophthora blight", "glycan_involvement": "N-glycosylation required for enzymatic activity.", "mechanism": "Degrades plant cell wall; N-glycosylation maintains stability and activity.", "protein": "PCIPG2", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "medium", "disease": "Grapevine dieback", "glycan_involvement": "N-glycosylation required for protein dimerisation and function.", "mechanism": "Protects fungal mycelia against host chitinase; N-glycosylation essential for homodimerisation.", "protein": "LtScp1", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Corn smut", "glycan_involvement": "N-glycosylation required for folding and virulence.", "mechanism": "Proper protein conformation and full pathogenic development depend on N-glycosylation.", "protein": "Pdi1", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Fusarium wilt", "glycan_involvement": "N-glycosylation of cell wall proteins essential for pathogenicity.", "mechanism": "Cell wall glycan modification; loss reduces virulence and alters cell morphology.", "protein": "Gnt2", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Phytophthora blight", "glycan_involvement": "N-glycosylation via Stt3 required for full virulence.", "mechanism": "Regulates fungal development, hyphal growth, and glycoprotein secretion.", "protein": "Stt3", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Anthracnose", "glycan_involvement": "N-glycosylation of effectors and cell wall proteins.", "mechanism": "Required for N-glycosylation of effectors and infection structure formation.", "protein": "Alg3", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Corn smut", "glycan_involvement": "N-glycosylation via glucosidase II activity.", "mechanism": "Alters cell wall material distribution and arrests infection hyphae growth.", "protein": "Gas1", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "medium", "disease": "General plant pathogenicity", "glycan_involvement": "N-glycosylation-dependent trafficking and secretion.", "mechanism": "Required for polarised growth and protein trafficking; deletion reduces N-glycoprotein secretion.", "protein": "Emp47", "relationship_type": "causal", "source_pmcid": "PMC12234393" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for PD-L1 stability and immune suppression.", "mechanism": "Glycosylation at N35/192/200/219 stabilizes PD-L1, enhances PD-1 binding, promotes immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation by FUT8 enhances immune suppression.", "mechanism": "N-glycosylation at N64/157/163/189 stabilizes PD-L2, prevents degradation, reinforces PD-1 interaction.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation regulates PD-1 function in T cells.", "mechanism": "N-glycosylation at N58 sustains PD-1 stability and membrane localization, required for PD-L1 interaction.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation supports CD47 stability and function.", "mechanism": "CD47 glycosylation promotes its cell surface expression, enabling tumor immune evasion via SIRP\u03b1 binding.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "7 N-glycosylation sites modulate B7-H4 stability.", "mechanism": "Glycosylation suppresses B7-H4 ubiquitination, increases stability, enhances immune suppression.", "protein": "B7-H4", "protein_enriched": { "function": "Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor ma", "gene_name": "VTCN1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G39188ZX", "G41247ZX" ], "uniprot_id": "Q7Z7D3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for B7-H6 function.", "mechanism": "N-glycosylation at N43/N208 is essential for NK cell activation and tumor progression.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation enhances PD-L1-mediated immune evasion.", "mechanism": "Glycosylation by B3GNT3 and MAN2A1 increases PD-L1 stability and expression in NSCLC cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12236040" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation and acetylation cooperate to upregulate PD-L1.", "mechanism": "Nucleo-cytosolic acetyl-CoA promotes PD-L1 transcription via p300-induced acetylation and glycosylation, leading to immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12236040" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation interferes with B7-H4 degradation.", "mechanism": "Glycosylation stabilizes B7-H4, suppresses antitumor immunity, reduces efficacy of antibody-drug conjugates.", "protein": "B7-H4", "protein_enriched": { "function": "Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor ma", "gene_name": "VTCN1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G39188ZX", "G41247ZX" ], "uniprot_id": "Q7Z7D3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "medium", "disease": "B-cell lymphoma", "glycan_involvement": "N-glycosylation by GLT1D1 increases PD-L1 stability.", "mechanism": "GLT1D1-induced glycosylation stabilizes PD-L1, promotes immunosuppression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12236040" }, { "confidence": "high", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "Accumulation of immature N-glycans and hybrid-type species in serum glycoproteins.", "mechanism": "MAN2A2 variants impair N-glycan maturation, affecting neurodevelopmental processes.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Intellectual Disability", "glycan_involvement": "Impaired N-glycosylation in serum and likely neuronal glycoproteins.", "mechanism": "Defective MAN2A2 disrupts glycoprotein processing, impacting cognitive function.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (MAN2A2-CDG)", "glycan_involvement": "Accumulation of immature and hybrid-type N-glycans; defective glycan trimming.", "mechanism": "Pathogenic MAN2A2 variants cause CDG with neurological and psychiatric features.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Congenital Dyserythropoietic Anemia Type II", "glycan_involvement": "Absence of complex N-glycans on erythrocyte glycoproteins.", "mechanism": "MAN2A1 deficiency leads to lack of complex N-glycans on erythrocyte surface.", "protein": "MAN2A1", "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Loss of tri-antennary and fucosylated N-glycans critical for spermatogenesis.", "mechanism": "MAN2A2 deficiency impairs spermatogenic cell adhesion via altered N-glycan structures.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "medium", "disease": "Psychiatric Disorders (bipolar, social withdrawal)", "glycan_involvement": "Altered glycosylation in neuronal glycoproteins.", "mechanism": "MAN2A2-CDG patients show psychiatric symptoms due to glycosylation defects in CNS.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12238240" }, { "confidence": "medium", "disease": "Congenital Disorder of Glycosylation (MAN2A2-CDG)", "glycan_involvement": "Normal transferrin glycosylation in MAN2A2-CDG patient; not a sensitive marker here.", "mechanism": "Transferrin glycoform analysis used to assess glycosylation status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12238240" }, { "confidence": "low", "disease": "Metabolic syndrome (context: high fat diet, mouse)", "glycan_involvement": "Increase in oligomannose, decrease in complex/fucosylated/sialylated N-glycans.", "mechanism": "Altered glycosylation of PTPRJ correlates with MAN2A1 reduction and metabolic changes.", "protein": "PTPRJ", "protein_enriched": { "function": "Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2 (PubMed:10821867, Pub", "gene_name": "PTPRJ", "glycan_count": 44, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G41071NU", "G62765YT", "G87661QW", "G57321FI", "G07246CJ", "G27058EU", "G29184RN", "G42124LM", "G80479JV", "G80920RR", "G85282JO", "G75568BH", "G02815KT", "G22310AV", "G47644PP", "G48414YA", "G59626AS", "G70619PT", "G79666IR", "G84452RH", "G90659AW", "G95865ZB", "G10486CT", "G42788ZD", "G43417UB", "G06356OH", "G11629QQ", "G15169WU", "G40508QH", "G36145AL", "G40379SA", "G82501QM", "G39471UU", "G67031OU", "G69834CE", "G83633GK", "G40926MX", "G05962QB", "G31852PQ", "G37509XX", "G41247ZX", "G08918WF", "G37692EO", "G49108TO" ], "uniprot_id": "Q12913" }, "relationship_type": "biomarker", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Congenital Disorder of Glycosylation (MAN2A2-CDG)", "glycan_involvement": "Hybrid-type N-glycans (e.g., Man5GlcNAc3) accumulate in patient serum.", "mechanism": "Accumulation of disease-specific hybrid-type N-glycans in serum is diagnostic.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12238240" }, { "confidence": "low", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "Restoration of N-glycan maturation could ameliorate neurodevelopmental symptoms.", "mechanism": "MAN2A2 is highly expressed in brain; targeting glycosylation pathways may be therapeutic.", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12238240" }, { "confidence": "high", "disease": "Epidermolysis bullosa acquisita", "glycan_involvement": "Type VII collagen is a glycoprotein; glycosylation may affect antigenicity and autoantibody binding.", "mechanism": "Autoantibodies target type VII collagen, disrupting anchoring fibrils at the dermal-epidermal junction, leading to skin fragility and blistering.", "protein": "Type VII collagen", "relationship_type": "causal", "source_pmcid": "PMC12239270" }, { "confidence": "high", "disease": "Recessive dystrophic epidermolysis bullosa", "glycan_involvement": "Glycosylation is critical for type VII collagen stability and function in the basement membrane.", "mechanism": "Genetic mutations in COL7A1 (encoding type VII collagen) cause loss of functional anchoring fibrils, resulting in severe blistering and scarring.", "protein": "Type VII collagen", "relationship_type": "causal", "source_pmcid": "PMC12239270" }, { "confidence": "medium", "disease": "Squamous cell carcinoma", "glycan_involvement": "Altered glycosylation may contribute to chronic inflammation and carcinogenesis.", "mechanism": "Chronic injury and scarring in severe EB (due to type VII collagen dysfunction) increase risk of aggressive SCC.", "protein": "Type VII collagen", "relationship_type": "biomarker", "source_pmcid": "PMC12239270" }, { "confidence": "high", "disease": "ASCVD", "glycan_involvement": "Collagen IV is glycosylated; glycosylation may affect stability and turnover.", "mechanism": "Elevated serum levels predict increased ASCVD risk in MASLD patients, reflecting systemic fibrosis and inflammation.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC12241792" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences extracellular matrix deposition.", "mechanism": "Serum levels correlate with degree of hepatic fibrosis.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Specific glycosylation isomer detected by Wisteria floribunda agglutinin.", "mechanism": "Serum M2BPGi reflects liver fibrosis severity.", "protein": "Mac-2-binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosaminoglycan structure is essential for function.", "mechanism": "Elevated levels indicate extracellular matrix remodeling in fibrosis.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "ASCVD", "glycan_involvement": "N-glycosylation modulates fibrinogen function and clearance.", "mechanism": "Pro-coagulant state in MASLD increases ASCVD risk via elevated fibrinogen.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "ASCVD", "glycan_involvement": "N-glycosylation critical for secretion and activity.", "mechanism": "Activation of coagulation factors contributes to thrombosis risk in MASLD.", "protein": "Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "ASCVD", "glycan_involvement": "Glycosylation affects stability and inhibitory activity.", "mechanism": "Elevated PAI-1 in MASLD promotes pro-thrombotic state, increasing ASCVD risk.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "ASCVD", "glycan_involvement": "Glycosylation required for multimerization and activity.", "mechanism": "Lower adiponectin in MASLD may reduce anti-inflammatory protection, increasing ASCVD risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12241792" }, { "confidence": "low", "disease": "ASCVD", "glycan_involvement": "Glycosylation influences secretion and receptor binding.", "mechanism": "Elevated leptin in MASLD may promote vascular inflammation and atherogenesis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12241792" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect interaction with cardiac extracellular matrix.", "mechanism": "Serum levels correlate with cardiac pressures and prognosis.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC12241792" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Higher O-glycosylation (especially sialylation) of apoE correlates with lower tau pathology", "mechanism": "ApoE glycosylation levels in CSF are inversely associated with tau pathology biomarkers (t-tau, p-tau181)", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation at specific sites reduces tau and p-tau181 levels", "mechanism": "Greater glycosylation of apoE4 isoform is associated with reduced tau pathology, especially in APOE \u03b54/\u03b54 carriers", "protein": "Apolipoprotein E (apoE)", "relationship_type": "protective", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Reduced secondary O-glycosylation correlates with disease progression", "mechanism": "Lower secondary glycosylation of apoE in CSF is associated with MCI and cognitive decline", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Loss of sialylation/glycosylation impairs A\u03b2 binding and clearance", "mechanism": "Less glycosylated apoE4 may have reduced binding to A\u03b2, impairing plaque clearance and increasing tau phosphorylation", "protein": "Apolipoprotein E (apoE)", "relationship_type": "causal", "source_pmcid": "PMC12243426" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation in plasma may reflect brain pathology", "mechanism": "Plasma apoE glycosylation is lower than CSF; higher plasma apoE glycosylation weakly associated with lower CSF A\u03b21-42", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Reduced O-glycosylation marks early disease state", "mechanism": "Lower CSF secondary apoE glycosylation in MCI compared to cognitively normal individuals", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "low", "disease": "Niemann-Pick Type C disease", "glycan_involvement": "Sialic acid addition on O-glycans marks early pathology", "mechanism": "Increased sialylation of neuronal apoE correlates with increased A\u03b21-42 before neurological symptoms", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-GlcNAc-Gal modification reduces amyloidogenic processing", "mechanism": "O-glycosylation of APP may inhibit A\u03b2 production", "protein": "Amyloid-\u03b2 precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sialic acids on O-glycans modulate protein-protein interactions", "mechanism": "Sialylation of apoE reduces its binding to heparan sulfate proteoglycans, potentially limiting A\u03b2 aggregation and tau propagation", "protein": "Apolipoprotein E (apoE)", "relationship_type": "protective", "source_pmcid": "PMC12243426" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Reduced sialylation is associated with disease state", "mechanism": "A less-sialylated form of apoE is more prevalent in AD subjects than controls", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker", "source_pmcid": "PMC12243426" }, { "confidence": "high", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycosylation at multiple sites; truncated core N-glycans upon ALG3/ALG12 deletion", "mechanism": "Cnb1 glycosylation is required for virulence; truncated N-glycans reduce protein stability and function.", "protein": "Cnb1", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "high", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycosylation at multiple sites; truncated core N-glycans upon ALG3/ALG12 deletion", "mechanism": "Gic1 glycosylation is essential for virulence; loss of N-glycosylation impairs function.", "protein": "Gic1", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "high", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycosylation at multiple sites; truncated core N-glycans upon ALG3/ALG12 deletion", "mechanism": "Glx glycosylation is required for hydrogen peroxide production and virulence.", "protein": "Glx (glyoxal oxidase)", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "high", "disease": "Reduced fungal virulence", "glycan_involvement": "Initiates \u03b1-1,3-mannose addition in N-glycan biosynthesis; deletion truncates core N-glycans", "mechanism": "Alg3 deletion leads to truncated N-glycans, affecting glycoprotein maturation and virulence.", "protein": "Alg3", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "high", "disease": "Reduced fungal virulence", "glycan_involvement": "Adds \u03b1-1,6-mannose in N-glycan biosynthesis; deletion truncates core N-glycans", "mechanism": "Alg12 deletion truncates core N-glycans, reducing glycoprotein stability and virulence.", "protein": "Alg12", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "medium", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycosylation; transfer of Glc3Man9GlcNAc2 to asparagine residues", "mechanism": "Ost complex transfers N-glycans to proteins; defects reduce virulence and growth.", "protein": "Ost complex", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "medium", "disease": "Cell wall integrity defect", "glycan_involvement": "O-glycosylation; transfer of mannose to serine/threonine residues", "mechanism": "Pmt complex mediates O-mannosylation; deletion impairs cell wall integrity and growth.", "protein": "Pmt complex", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "medium", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycan trimming; affects glycoprotein maturation", "mechanism": "Mns1 mannosidase activity is required for proper N-glycan maturation and virulence.", "protein": "Mns1", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "medium", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycan trimming; affects glycoprotein maturation", "mechanism": "Mnl2 mannosidase activity is required for N-glycan maturation and virulence.", "protein": "Mnl2", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "medium", "disease": "Reduced fungal virulence", "glycan_involvement": "N-glycosylation; glycan extension", "mechanism": "Hoc1 glycosyltransferase activity is required for proper glycan structure and virulence.", "protein": "Hoc1", "relationship_type": "causal", "source_pmcid": "PMC12244721" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect synaptic vesicle function and PET ligand binding.", "mechanism": "SV2A PET imaging ([11C]UCB-J) quantifies synaptic density, which is reduced in AD.", "protein": "SV2A (Synaptic Vesicle Glycoprotein 2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "CSF neurogranin levels are increased in AD and correlate with reduced synaptic density.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF syntaxin-7 levels are associated with lower synaptic density in AD; involved in vesicle endocytosis.", "protein": "Syntaxin-7", "protein_enriched": { "function": "May be involved in protein trafficking from the plasma membrane to the early endosome (EE) as well as in homotypic fusion of endocytic organelles. Mediates the endocytic trafficking from early endosom", "gene_name": "STX7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15400" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF PEBP-1 levels are associated with lower synaptic density in AD; modulates kinase signaling and neurotransmission.", "protein": "PEBP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF AP2B1 levels are associated with lower synaptic density in AD; involved in endocytosis.", "protein": "AP2B1", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF GDI-1 levels are associated with lower synaptic density in AD.", "protein": "GDI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF \u03b3-synuclein levels are associated with lower synaptic density in AD.", "protein": "\u03b3-Synuclein", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "SNCG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O76070" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Higher CSF syntaxin-1B levels are associated with lower synaptic density in AD.", "protein": "Syntaxin-1B", "protein_enriched": { "function": "Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a co", "gene_name": "TNFRSF14", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q92956" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "NPTX1 and NPTX2 are secreted glycoproteins; glycosylation may affect secretion and receptor interactions.", "mechanism": "CSF levels of neuronal pentraxins are decreased in AD and correlate with cognitive decline, but not with synaptic density in this study.", "protein": "Neuronal Pentraxin 1/2/Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies / Frontotemporal dementia / Parkinson's disease / Huntington's disease", "glycan_involvement": "SV2A glycosylation may affect synaptic vesicle function and PET ligand binding.", "mechanism": "SV2A PET imaging shows reduced synaptic density in these neurodegenerative diseases.", "protein": "SV2A (Synaptic Vesicle Glycoprotein 2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12245979" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation required for secretion and function as C1 esterase inhibitor.", "mechanism": "Upregulated in late-stage DMD muscle; hub gene in immune response and complement activation.", "protein": "SERPING1", "relationship_type": "biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates protease activity and substrate interactions.", "mechanism": "Promotes ECM remodeling, fibrosis, and muscle fiber loss; strongly upregulated in DMD and by BMP4.", "protein": "ADAM12", "protein_enriched": { "function": "Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors (By simil", "gene_name": "ADAM12", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43184" }, "relationship_type": "causal", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and signaling.", "mechanism": "Upregulated in DMD muscle; involved in WNT/BMP signaling and bone morphogenesis.", "protein": "SFRP4", "protein_enriched": { "function": "Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell ", "gene_name": "SFRP4", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G72747WU", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G06356OH", "G10486CT", "G18647XP", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G41071NU", "G42124LM", "G45395BF", "G47644PP", "G51640FO", "G65184UU", "G72291OX", "G72735IY", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G84452RH", "G90659AW", "G95177YH", "G95865ZB", "G34989PA", "G84225JN" ], "uniprot_id": "Q6FHJ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct glycosylation, but interacts with glycoprotein receptors.", "mechanism": "Upregulated by BMP4; mediates TGF\u03b2/BMP signaling, represses myogenic microRNAs, drives disease transcriptome.", "protein": "SMAD8 (SMAD9)", "protein_enriched": { "function": "Does not exhibit calcium-activated chloride channel (CaCC) activity", "gene_name": "ANO8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HCE9" }, "relationship_type": "causal", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "GPCR glycosylation affects cell surface expression and signaling.", "mechanism": "Most upregulated transcript in late-stage DMD; represses inflammation via TGF\u03b21 induction.", "protein": "HCAR2", "protein_enriched": { "function": "High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhi", "gene_name": "MTNR1B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P49286" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12245985" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation regulates secretion and proteolytic activity.", "mechanism": "Upregulated in late-stage DMD; promotes myofiber injury, fibrosis, and activates TGF\u03b2.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Secretory granule glycoprotein; glycosylation required for sorting and function.", "mechanism": "Highly upregulated in DMD muscle; involved in cytokine/chemoattractant activity.", "protein": "SCG2", "protein_enriched": { "function": "Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules", "gene_name": "SCG2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13521" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation influences stability and inhibitory activity.", "mechanism": "Upregulated in DMD muscle; member of serine protease inhibitor family.", "protein": "SERPINB12", "protein_enriched": { "function": "May play a role in the proliferation or differentiation of keratinocytes", "gene_name": "SERPINB13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIV8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "No direct evidence; possible indirect effects via glycoprotein interactions.", "mechanism": "Strongly downregulated in DMD and BMP4-stimulated muscle; involved in neuromuscular junction function.", "protein": "UNC13C", "protein_enriched": { "function": "Cleaves 'Lys-63'-linked poly-ubiquitin chains, and with lesser efficiency 'Lys-48'-linked poly-ubiquitin chains (in vitro). May act as a deubiquitinating enzyme", "gene_name": "JOSD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8TAC2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12245985" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation essential for MHC class I stability and immune recognition.", "mechanism": "Most downregulated transcript in late-stage DMD; involved in antigen presentation.", "protein": "HLA-A", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12245985" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "Elevated FA3G3S3 glycan structure in tumor-derived bHCG", "mechanism": "Serum marker for TGCT; altered glycosylation patterns in disease", "protein": "beta-human chorionic gonadotropin (bHCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "N-glycosylation relevant for biomarker function", "mechanism": "Serum marker for TGCT; glycosylation status may affect detection", "protein": "alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "medium", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "Changes in multiantennary N-glycans in plasma", "mechanism": "Altered glycosylation in malignancy; may contribute to detected N-glycan changes", "protein": "alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "Not directly glycosylated; cfDNA methylation used as marker", "mechanism": "Hypermethylation of cfDNA in blood plasma is diagnostic for NSE", "protein": "RASSF1A", "protein_enriched": { "function": "Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When ass", "gene_name": "RASSF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NS23" }, "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "Not directly glycosylated; cfDNA methylation used as marker", "mechanism": "Hypermethylation of cfDNA in seminal plasma is diagnostic for NSE", "protein": "PRSS21", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "Not glycosylated; methylation status is key", "mechanism": "Hypomethylation in blood plasma cfDNA and hypermethylation in seminal plasma cfDNA are diagnostic for NSE", "protein": "LINE-1", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "medium", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "N-glycan structure altered in disease", "mechanism": "Decreased abundance in NSE patient plasma; may reflect altered glycoprotein expression", "protein": "A2G2S2 glycan (GP18)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "N-glycan structure elevated in disease", "mechanism": "Elevated in tumor cell-derived bHCG, associated with malignancy progression", "protein": "FA3G3S3 glycan (GP34)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Nonseminomatous testicular germ cell tumor (NSE)", "glycan_involvement": "N-glycan structure altered in disease", "mechanism": "Increased in NSE patient plasma; linked to tumor-derived bHCG", "protein": "FA3G3S3 glycan (GP34)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "medium", "disease": "Teratoma", "glycan_involvement": "N-glycan structure altered in disease", "mechanism": "Altered abundance in plasma may aid detection of teratoma subtype", "protein": "A2G2S2 glycan (GP18)", "relationship_type": "biomarker", "source_pmcid": "PMC12247211" }, { "confidence": "high", "disease": "Growth retardation under hyperosmotic stress", "glycan_involvement": "O-glycosylation of proteins enhances growth and energy storage.", "mechanism": "GALNT9 mediates O-glycan biosynthesis, promoting fat deposition and muscle growth in fast-growing tilapia.", "protein": "GALNT9", "protein_enriched": { "function": "", "gene_name": "RNF148", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N7C7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "high", "disease": "Growth retardation under hyperosmotic stress", "glycan_involvement": "Glycosylation may regulate PLXNB2 function in growth signaling.", "mechanism": "PLXNB2 is linked to growth plate development, chondrogenesis, and skeletal growth.", "protein": "PLXNB2", "relationship_type": "causal", "source_pmcid": "PMC12249547" }, { "confidence": "medium", "disease": "Energy metabolism defects", "glycan_involvement": "Potential glycosylation affects DNM1 stability and function.", "mechanism": "DNM1 expression promotes cell growth and energy production, especially in galactose metabolism.", "protein": "DNM1", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "medium", "disease": "Muscle growth deficiency", "glycan_involvement": "Glycosylation may modulate BPGM activity.", "mechanism": "BPGM upregulation enhances glycolysis, supporting muscle growth in fast-growing fish.", "protein": "BPGM", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "medium", "disease": "Growth retardation under hyperosmotic stress", "glycan_involvement": "Possible O-glycosylation affects microtubule interactions.", "mechanism": "MAP7 is involved in cytoskeletal organization, impacting cell growth.", "protein": "MAP7", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "medium", "disease": "Energy metabolism defects", "glycan_involvement": "Glycosylation may affect mitochondrial localization.", "mechanism": "MTFR2 regulates mitochondrial fission, influencing energy metabolism and growth.", "protein": "MTFR2", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "medium", "disease": "Growth retardation under hyperosmotic stress", "glycan_involvement": "O-glycosylation may regulate kinase activity.", "mechanism": "NUAK1 modulates cell growth and stress response.", "protein": "NUAK1", "protein_enriched": { "function": "Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS", "gene_name": "NUAK1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60285" }, "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "low", "disease": "Apoptosis dysregulation", "glycan_involvement": "Glycosylation may affect receptor stability.", "mechanism": "ESRRG influences steroid hormone signaling and apoptosis.", "protein": "ESRRG", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "low", "disease": "Energy metabolism defects", "glycan_involvement": "Glycosylation modulates channel function.", "mechanism": "KCNJ8 regulates potassium channel activity, impacting ATP generation and growth.", "protein": "KCNJ8", "relationship_type": "biomarker", "source_pmcid": "PMC12249547" }, { "confidence": "low", "disease": "Cancer (breast)", "glycan_involvement": "Glycosylation may regulate FHIT stability and tumor suppressor activity.", "mechanism": "FHIT acts as a tumor suppressor; its expression is linked to cell growth and apoptosis.", "protein": "FHIT", "relationship_type": "tumor suppressor", "source_pmcid": "PMC12249547" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; N- and O-glycans facilitate binding and immune evasion.", "mechanism": "Mediates viral entry into host cells via binding to ACE2 receptor.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Interacts with -OH and -NH groups of AGEs and host glycans, promoting viral entry.", "mechanism": "Enhanced binding to host cells in T2D due to increased AGEs and glycan-rich environments.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of IgG Fc region increases during infection.", "mechanism": "Increased glycosylated IgG (1775 cm\u22121 FTIR band) indicates COVID-19-induced inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12249686" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Non-enzymatic glycation increases -OH and -NH groups, facilitating spike binding.", "mechanism": "AGE accumulation enhances host cell susceptibility to viral entry and inflammation.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Result from chronic hyperglycemia-induced protein glycation.", "mechanism": "AGEs propagate oxidative stress and inflammation, worsening diabetes complications.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, affecting spike binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2 spike glycoprotein.", "protein": "Angiotensin-Converting Enzyme 2 (ACE2)", "protein_enriched": { "function": "Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis (P", "gene_name": "ACE2", "glycan_count": 349, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G03644CB", "G04657PL", "G05049YU", "G06247RL", "G07246CJ", "G07755XJ", "G07799LX", "G08293MJ", "G08918WF", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10846ZT", "G12341GU", "G12580WI", "G13131HA", "G14972EH", "G15038BD", "G15486FH", "G16175ZV", "G19379ID", "G19464WF", "G19517GM", "G20528HD", "G20956ZV", "G22768VO", "G25079LO", "G25451PN", "G25987BV", "G27058EU", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G29651HS", "G30740WO", "G31852PQ", "G32788FZ", "G35029YA", "G35541EV", "G36670VW", "G37399XV", "G37412TK", "G39446WN", "G39471UU", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G42466VF", "G43223CG", "G43669FQ", "G44211QA", "G44753VC", "G44953PJ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G49284IH", "G49755GI", "G49955PK", "G50073PQ", "G54600FO", "G55132BD", "G55382TU", "G56518TU", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59937CP", "G60033FS", "G60834IK", "G60923RB", "G62765YT", "G62792OG", "G65184UU", "G67324HN", "G68318VE", "G68490OW", "G69364JQ", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G72791KH", "G75568BH", "G76295SF", "G79666IR", "G80075MS", "G80475RE", "G80669SJ", "G80735OA", "G80920RR", "G81124ET", "G82364UA", "G82443XX", "G83460ZZ", "G83555HU", "G83646BJ", "G85144OK", "G85282JO", "G85740DB", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G88725PI", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G95177YH", "G95835XS", "G43417UB", "G75365RL", "G94583DZ", "G93579XB", "G98896IU", "G32926LW", "G41126SR", "G43638QT", "G54417MJ", "G61751GZ", "G98596OT", "G29068FM", "G23729WG", "G87384DY", "G27391WQ", "G58001LT", "G10756ZZ", "G23505EP", "G79941IJ", "G80728XN", "G81315DD", "G00273SJ", "G01485JJ", "G02528FI", "G10773YW", "G10819WX", "G11314AS", "G16125XL", "G23719VF", "G24528MX", "G27915IV", "G29905OR", "G30970QQ", "G37509XX", "G37995HC", "G43769HG", "G47644PP", "G49739MP", "G49906RN", "G59924QI", "G63041LO", "G72747WU", "G73686WG", "G77547TA", "G80479JV", "G85269DF", "G85554PZ", "G95865ZB", "G98611JV", "G40926MX", "G48414YA", "G55220VL", "G68008QO", "G81006GJ", "G01160VV", "G05962QB", "G06969ZX", "G22573RC", "G27947YN", "G34989PA", "G37818NZ", "G60967DT", "G70888PK", "G91208VE", "G93718GY", "G00031MO", "G00033MO", "G00420UH", "G01457KB", "G01614ZM", "G02030ZB", "G03127AL", "G03382KH", "G04791QM", "G05642HQ", "G05724UK", "G06110VR", "G06356OH", "G07410AW", "G07483YN", "G08146BT", "G10256JP", "G10691MJ", "G11041DA", "G11457RF", "G11629QQ", "G11637WL", "G11870QZ", "G14994KB", "G15169WU", "G16828VN", "G20732FY", "G21507RO", "G22140GZ", "G22310AV", "G22355FZ", "G23432EQ", "G23863VK", "G24835MQ", "G24954UD", "G25481DT", "G25637MV", "G26403SG", "G27251WT", "G28052FT", "G28106CM", "G29880MM", "G29931IJ", "G30159WR", "G31153XO", "G31596VW", "G31916IQ", "G32550BI", "G33609NS", "G34617SM", "G34838RM", "G37442IW", "G37868ZX", "G37881RL", "G39018CC", "G39188ZX", "G39213VZ", "G39595FH", "G39943KJ", "G41611UP", "G42358LZ", "G43694RQ", "G44215PV", "G45359RY", "G45495MK", "G46687AB", "G46831QF", "G47518TP", "G49108TO", "G49299ZV", "G49644CL", "G49874UX", "G50045TK", "G50757KG", "G51640FO", "G52527GH", "G52934AK", "G55484MX", "G56102PZ", "G56749GV", "G56903ZB", "G57818FI", "G57888GL", "G58667NI", "G59126YU", "G59456VR", "G59536GA", "G60070LT", "G60145BJ", "G60605ZN", "G60890ZT", "G62461SM", "G63628AV", "G64394MX", "G64527OM", "G64973KT", "G66676MI", "G66760KM", "G66937TJ", "G68209WQ", "G68698AP", "G72667IM", "G72735IY", "G72797UR", "G74430RZ", "G74722FL", "G74724QE", "G75594YZ", "G75798PH", "G75983OB", "G76163CP", "G78059CC", "G79568CQ", "G80223IX", "G80393PG", "G80858MF", "G80966KZ", "G81263BG", "G81295CK", "G82119TF", "G82252QI", "G82348BZ", "G82942ZJ", "G83204BU", "G83295QG", "G83892WB", "G83945MQ", "G84452RH", "G84467IZ", "G84820NF", "G85542KD", "G85608AG", "G87015RU", "G87618BG", "G88417ED", "G89098OM", "G89319AW", "G90093AU", "G90789YQ", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G91875JA", "G92684AL", "G93656SY", "G93994MR", "G94435QH", "G94854LT", "G97876DH", "G99074EO", "G99342HD", "G99858XP", "G99966GV", "G99969SS" ], "uniprot_id": "Q9BYF1" }, "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Altered glycosylation patterns reflect inflammation and disease state.", "mechanism": "Increased glycosylated IgG in T2D patients, especially with COVID-19 infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12249686" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates tissue tropism and immune response.", "mechanism": "Spike protein binding to ACE2 in cardiovascular tissues may exacerbate disease.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Protein glycation alters vascular protein function.", "mechanism": "AGEs contribute to vascular inflammation and atherosclerosis.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12249686" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation provides binding sites for metformin interaction.", "mechanism": "Metformin may bind spike protein via NH groups, blocking viral entry.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12249686" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Recognizes glycosylated antigens, mediates antigen uptake.", "mechanism": "CD206 is upregulated in non-classical monocytes after intermittent prednisone, indicating M2-like anti-inflammatory polarization.", "protein": "CD206 (Mannose Receptor)", "protein_enriched": { "function": "May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity. Internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via ", "gene_name": "MRC2", "glycan_count": 50, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G05049YU", "G10486CT", "G18647XP", "G28541PG", "G39446WN", "G90659AW", "G49108TO", "G83460ZZ", "G27058EU", "G41071NU", "G42124LM", "G45395BF", "G80920RR", "G57321FI", "G00912UN", "G05962QB", "G57776ZS", "G62765YT", "G70232NH", "G70441OD", "G79666IR", "G90382BL", "G04657PL", "G14972EH", "G25418HZ", "G27126ED", "G43223CG", "G46691LC", "G60177UT", "G66621EA", "G80223IX", "G81263BG", "G82830MN", "G84452RH", "G89098OM", "G96416FQ", "G05724UK", "G64527OM", "G70101JE", "G00406II", "G06110VR", "G08918WF", "G23863VK", "G29299MO", "G59924QI", "G65092SV", "G70619PT", "G86880BF", "G87123QX" ], "uniprot_id": "Q9UBG0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Heavily glycosylated; glycosylation affects receptor shedding and function.", "mechanism": "CD163 is increased in intermediate monocytes in both untreated and prednisone-treated MD patients, marking M2-like anti-inflammatory state.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12250195" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "O-mannosylation critical for function; defective glycosylation leads to disease.", "mechanism": "Mutations in dystroglycan complex genes cause DMD by disrupting muscle membrane stability.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12250195" }, { "confidence": "high", "disease": "Limb-Girdle Muscular Dystrophy (LGMD2C/R5)", "glycan_involvement": "Glycosylation required for membrane localization and stability.", "mechanism": "Mutations in sarcoglycan genes impair glycoprotein complex, causing muscle degeneration.", "protein": "Sarcoglycan complex", "relationship_type": "causal", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Muscle Fibrosis", "glycan_involvement": "No direct glycosylation; regulates glycoprotein gene expression.", "mechanism": "CEBPB upregulated after prednisone; promotes collagen I production and senescence in monocytes/macrophages, contributing to fibrosis.", "protein": "CEBPB", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Inflammation (muscle)", "glycan_involvement": "Glycosylation modulates cell surface expression and immune signaling.", "mechanism": "CD86 decreased in classical monocytes after prednisone, indicating reduced pro-inflammatory activation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12250195" }, { "confidence": "high", "disease": "Muscle Fibrosis", "glycan_involvement": "Glycosylation affects fibril formation and tissue deposition.", "mechanism": "Collagen I overproduction by monocytes/macrophages contributes to fibrotic tissue in MD.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Muscle Fibrosis", "glycan_involvement": "Glycosylation modulates enzyme activity and secretion.", "mechanism": "MMP2 upregulated after prednisone; involved in ECM remodeling and fibrosis progression.", "protein": "MMP2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Muscle Fibrosis", "glycan_involvement": "Glycosylation required for receptor binding and stability.", "mechanism": "IL4 signaling promotes M2 macrophage polarization and tissue repair, but may also stimulate fibro/adipogenic progenitors.", "protein": "IL4", "protein_enriched": { "function": "Cytokine secreted primarily by mast cells, T-cells, eosinophils, and basophils that plays a role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-ce", "gene_name": "IL4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05112" }, "relationship_type": "protective", "source_pmcid": "PMC12250195" }, { "confidence": "medium", "disease": "Muscle Fibrosis", "glycan_involvement": "Glycosylation affects cytokine-receptor interactions.", "mechanism": "IL13 signaling supports anti-inflammatory response and matrix remodeling, but may contribute to fibrosis under chronic stimulation.", "protein": "IL13", "protein_enriched": { "function": "Cytokine that plays important roles in allergic inflammation and immune response to parasite infection (PubMed:8096327, PubMed:8097324). Synergizes with IL2 in regulating interferon-gamma synthesis (P", "gene_name": "IL13", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35225" }, "relationship_type": "protective", "source_pmcid": "PMC12250195" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation-dependent function in cell\u2013matrix interaction and immune modulation.", "mechanism": "Promotes glioma cell viability, clonogenicity, invasion, and tumor growth; silencing inhibits tumor progression.", "protein": "COLEC12", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation modulates receptor-mediated signaling and immune interactions.", "mechanism": "Supports glioma cell proliferation, stemness, and invasion; knockdown reduces tumor growth.", "protein": "LY75", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation affects ligand binding and immune cell recruitment.", "mechanism": "Facilitates glioma cell growth and migration; silencing impairs tumorigenic properties.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Heparan sulfate glycosylation mediates cell signaling and microenvironment interactions.", "mechanism": "Maintains glioma cell viability and invasiveness; knockdown suppresses tumor progression.", "protein": "GPC4", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Involved in glycan processing, impacting protein glycosylation and cell behavior.", "mechanism": "Essential for glioma cell survival and proliferation; silencing reduces tumor growth.", "protein": "RENBP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Proteoglycan glycosylation modulates extracellular matrix and signaling.", "mechanism": "Promotes glioma cell proliferation, stemness, and invasion; knockdown inhibits tumorigenesis.", "protein": "SRGN", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation regulates extracellular matrix interactions.", "mechanism": "Supports glioma cell growth and migration; silencing impairs tumor progression.", "protein": "FMOD", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "medium", "disease": "Immune evasion in GBM", "glycan_involvement": "Glycosylation modulates immune checkpoint function and expression.", "mechanism": "Upregulated in high-risk GBM; promotes immune checkpoint-mediated immune evasion.", "protein": "PDCD1LG2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "medium", "disease": "Immune evasion in GBM", "glycan_involvement": "Glycosylation affects PD-L1 stability and immune interactions.", "mechanism": "Elevated in high-risk GBM; associated with immune suppression and potential immunotherapy response.", "protein": "CD274", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12257128" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Enzyme in glycan degradation; alters tumor immune microenvironment.", "mechanism": "Drives glycolysis-dependent tumor growth and suppresses T-cell infiltration.", "protein": "Hexosaminidase B", "relationship_type": "causal", "source_pmcid": "PMC12257128" }, { "confidence": "high", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "Non-enzymatic glycation (AGE formation) increases RAGE activation.", "mechanism": "Binding of AGEs to RAGE exacerbates inflammation and oxidative stress, promoting endothelial dysfunction.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "high", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "AGEs interfere with eNOS function via glycation.", "mechanism": "AGEs inhibit eNOS activity and NO production, leading to vascular injury.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "high", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "O-GlcNAc glycosylation of proteins is upregulated.", "mechanism": "Hyperglycemia increases OGT and O-GlcNAcylation, affecting endothelial cell apoptosis and ROS accumulation.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "AGEs trigger signaling affecting moesin function.", "mechanism": "Moesin mediates AGE-induced endothelial barrier disruption via GLP-1R/cAMP/PKA pathway.", "protein": "Moesin", "protein_enriched": { "function": "Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers a", "gene_name": "MSN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P26038" }, "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation and SUMOylation modulate VEGFR2 activity.", "mechanism": "SUMOylation and glycosylation of VEGFR2 regulate abnormal angiogenesis in diabetes.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "Interacts with glycation-modified proteins.", "mechanism": "Peroxidase inhibits eNOS phosphorylation, worsening AGEs-induced vascular dysfunction.", "protein": "Peroxidase", "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "Modulates downstream signaling affected by glycosylation.", "mechanism": "GLP-1R activation protects against AGE-induced endothelial barrier impairment.", "protein": "GLP-1R", "relationship_type": "protective", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "N-glycosylation of proteins is impaired.", "mechanism": "Inactivation leads to reduced insulin secretion and hyperglycemia.", "protein": "N-acetylglucosaminyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "medium", "disease": "Diabetic Endothelial Dysfunction", "glycan_involvement": "Removes O-GlcNAc from proteins, affecting function.", "mechanism": "Overexpression reduces insulin secretion and glucose tolerance.", "protein": "OGA", "protein_enriched": { "function": "Cleaves GlcNAc but not GalNAc from O-glycosylated proteins (PubMed:11148210, PubMed:11788610, PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839, PubMed:37962578). Deglycosylates a lar", "gene_name": "OGA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "O60502" }, "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Non-enzymatic glycation of proteins forms AGEs.", "mechanism": "AGEs induce apoptosis in pancreatic \u03b2-cells, reducing insulin synthesis and secretion, contributing to endothelial dysfunction.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12257670" }, { "confidence": "high", "disease": "Intestinal health (homeostasis)", "glycan_involvement": "O-glycans and N-glycans serve as substrates for beneficial bacteria; their degradation yields metabolites supporting gut health.", "mechanism": "Mucin glycan degradation by commensal bacteria produces SCFAs, stimulates mucus production, and regulates immune responses.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Gastrointestinal disease", "glycan_involvement": "Loss of O-glycan and N-glycan structures compromises barrier function.", "mechanism": "Excessive mucin glycan degradation disrupts the mucus barrier, allowing bacteria to access epithelial cells and trigger disease.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Mucus layer breakdown", "glycan_involvement": "Rapid degradation of fucosylated and larger O-glycans by R. torques.", "mechanism": "High abundance of Ruminococcus torques correlates with undesired mucus layer breakdown.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12258148" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Changes in mucin O-glycan degradation patterns reflect disease state.", "mechanism": "Altered abundance of mucin glycan-degrading bacteria (e.g., R. torques) is associated with IBD.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12258148" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "O-glycan degradation yields acetate and propionate, beneficial for metabolic health.", "mechanism": "Akkermansia muciniphila degrades mucin glycans, producing SCFAs that improve host energy metabolism.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12258148" }, { "confidence": "medium", "disease": "Gastrointestinal disease", "glycan_involvement": "High-mannose and fucosylated N-glycans require community-level degradation.", "mechanism": "Incomplete degradation of N-glycans by single bacteria may allow persistence of pathogenic glycan structures.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Intestinal health (homeostasis)", "glycan_involvement": "Complete O- and N-glycan degradation enables cross-feeding and SCFA generation.", "mechanism": "Synthetic bacterial communities fully degrade mucin glycans, supporting butyrate production and barrier integrity.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Mucus layer breakdown", "glycan_involvement": "Preferential degradation of fucosylated O-glycans.", "mechanism": "Overactive mucin glycan degradation by R. torques leads to thinning of the mucus layer.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Intestinal health (homeostasis)", "glycan_involvement": "Balanced O-glycan degradation maintains mucus layer and immune homeostasis.", "mechanism": "Akkermansia muciniphila stimulates mucus production and immune regulation via mucin glycan degradation.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12258148" }, { "confidence": "medium", "disease": "Gastrointestinal disease", "glycan_involvement": "Incomplete or excessive O- and N-glycan degradation alters barrier function.", "mechanism": "Disrupted microbial composition leads to inefficient mucin glycan degradation and disease.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12258148" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "AST is glycosylated, which may affect its stability and secretion.", "mechanism": "Elevated AST levels indicate hepatocellular injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260786" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate platelet function and clearance.", "mechanism": "Platelet count is used in FIB-4 scoring to assess fibrosis risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12260786" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "ALT is glycosylated, influencing its serum half-life.", "mechanism": "ALT elevation reflects hepatocyte damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260786" }, { "confidence": "high", "disease": "Clozapine toxicity", "glycan_involvement": "Glycosylation of alpha-1 acid glycoprotein modulates its drug-binding capacity.", "mechanism": "Acute infection increases alpha-1 acid glycoprotein, which binds clozapine and increases total plasma drug levels.", "protein": "alpha-1 acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12260851" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation state changes during inflammation, affecting function.", "mechanism": "Alpha-1 acid glycoprotein is upregulated during acute infection such as pneumonia.", "protein": "alpha-1 acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12260851" }, { "confidence": "medium", "disease": "Delirium", "glycan_involvement": "Glycosylation affects drug-binding and distribution.", "mechanism": "Elevated alpha-1 acid glycoprotein during infection increases clozapine binding, leading to altered free drug levels and neuropsychiatric symptoms.", "protein": "alpha-1 acid glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12260851" }, { "confidence": "medium", "disease": "Stroke/TIA-like symptoms", "glycan_involvement": "Glycosylation modulates protein-drug interactions.", "mechanism": "High alpha-1 acid glycoprotein during infection increases clozapine binding, which can mimic stroke/TIA symptoms due to toxicity.", "protein": "alpha-1 acid glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12260851" }, { "confidence": "medium", "disease": "Starvation hepatitis", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT reflects hepatocellular stress during starvation.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "medium", "disease": "Starvation hepatitis", "glycan_involvement": "ALT is glycosylated; glycan status may modulate enzyme activity and clearance.", "mechanism": "ALT elevation indicates hepatocyte injury due to extreme malnutrition.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "medium", "disease": "Starvation hepatitis", "glycan_involvement": "AST glycosylation may influence serum half-life.", "mechanism": "AST elevation parallels ALT, marking liver cell damage in starvation.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Refeeding hepatitis", "glycan_involvement": "Glycosylation state may change during metabolic shifts.", "mechanism": "GGT may rise during refeeding-induced hepatic stress.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Refeeding hepatitis", "glycan_involvement": "Glycosylation may affect ALT release and detection.", "mechanism": "ALT increases can signal hepatic injury during refeeding.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Refeeding hepatitis", "glycan_involvement": "Glycosylation may modulate AST function.", "mechanism": "AST elevation may indicate liver stress during refeeding.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Anorexia nervosa", "glycan_involvement": "Glycosylation impacts GGT stability in circulation.", "mechanism": "GGT levels may reflect chronic malnutrition-induced hepatic dysfunction.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Anorexia nervosa", "glycan_involvement": "Glycosylation may affect ALT's serum levels.", "mechanism": "ALT is a marker for liver injury in severe AN.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "low", "disease": "Anorexia nervosa", "glycan_involvement": "Glycosylation may influence AST's activity.", "mechanism": "AST elevation may occur in advanced AN due to hepatic stress.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12260872" }, { "confidence": "high", "disease": "Salmonellosis (gastroenteritis, invasive disease)", "glycan_involvement": "Antigenic glycan structure is targeted by vaccine-induced antibodies.", "mechanism": "Synthetic LPS outer core glycans, when used as vaccine antigens, elicit antibodies that bind Salmonella and enhance bactericidal activity.", "protein": "Lipopolysaccharide (LPS) outer core", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12261950" }, { "confidence": "high", "disease": "Foodborne Salmonella infection", "glycan_involvement": "Glycan epitope is the immunogen.", "mechanism": "Vaccination with LPS outer core glycans conjugated to mQ\u03b2 induces protective IgG responses in animal models.", "protein": "Lipopolysaccharide (LPS) outer core", "relationship_type": "protective", "source_pmcid": "PMC12261950" }, { "confidence": "high", "disease": "Salmonellosis (gastroenteritis, invasive disease)", "glycan_involvement": "Affects glycan display on bacterial surface.", "mechanism": "Inhibition of LptA/LptD by thanatin exposes LPS core glycans, enhancing antibody access and bactericidal activity.", "protein": "LPS transport proteins LptA and LptD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12261950" }, { "confidence": "high", "disease": "Salmonellosis (gastroenteritis, invasive disease)", "glycan_involvement": "OPS glycan is the immunogen; structural diversity limits cross-protection.", "mechanism": "OPS-based vaccines are effective but serovar-specific due to glycan variability.", "protein": "O-polysaccharide (OPS)", "relationship_type": "protective", "source_pmcid": "PMC12261950" }, { "confidence": "medium", "disease": "Multidrug-resistant Salmonella infection", "glycan_involvement": "Conserved glycan structure enables cross-serovar targeting.", "mechanism": "LPS outer core glycans are conserved and can be targeted for broad-spectrum vaccine development.", "protein": "Lipopolysaccharide (LPS) outer core", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12261950" }, { "confidence": "medium", "disease": "Foodborne Salmonella infection", "glycan_involvement": "Modifies glycan accessibility.", "mechanism": "Thanatin-mediated inhibition of LptA/LptD increases vaccine efficacy by exposing LPS core.", "protein": "LPS transport proteins LptA and LptD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12261950" }, { "confidence": "medium", "disease": "Salmonellosis (gastroenteritis, invasive disease)", "glycan_involvement": "Antibody recognition of glycan epitope.", "mechanism": "Antibodies against LPS outer core can serve as markers of exposure or immunity.", "protein": "Lipopolysaccharide (LPS) outer core", "relationship_type": "biomarker", "source_pmcid": "PMC12261950" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Altered glycosylation modulates PKM2 activity and inflammatory phenotype.", "mechanism": "Glycosylation of PKM2 regulates FLS proliferation, migration, invasion, and cytokine release.", "protein": "PKM2", "protein_enriched": { "function": "Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:2084", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation status affects AQP1 function in autophagy.", "mechanism": "K63-linked ubiquitination and glycosylation of AQP1 regulate autophagy in FLS.", "protein": "AQP1", "relationship_type": "causal", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation influences ICAM2-mediated cell adhesion and migration.", "mechanism": "METTL3-mediated m6A methylation and glycosylation of ICAM2 promote FLS migration and invasion.", "protein": "ICAM2", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM2 may play a role in lymphocyte recirculation by blocking LFA-1-dependent cell adhesion. It mediates a", "gene_name": "ICAM2", "glycan_count": 26, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G62765YT", "G22310AV", "G31852PQ", "G52527GH", "G80920RR", "G84452RH", "G11629QQ", "G37399XV", "G57888GL", "G82463GQ", "G31665QC", "G43089EG", "G47518TP", "G56784JY", "G75983OB", "G15169WU", "G24528MX", "G39619TI", "G43769HG", "G45395BF", "G57776ZS", "G82830MN", "G49108TO" ], "uniprot_id": "P13598" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Joint destruction", "glycan_involvement": "Glycosylation regulates MMP-9 secretion and enzymatic activity.", "mechanism": "IGF2BP3 promotes FLS migration/invasion via RRM2/Akt/MMP-9 pathway; glycosylation modulates MMP-9 activity.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation affects ENO1 stability and activity.", "mechanism": "High acetylation and glycosylation of ENO1 in RA PBMCs increases glycolytic energy supply for activated lymphocytes.", "protein": "ENOLASE 1 (ENO1)", "protein_enriched": { "function": "Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth c", "gene_name": "ENO1", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G45504EY", "G64409MC", "G92275SC", "G49108TO", "G29068FM", "G80920RR" ], "uniprot_id": "P06733" }, "relationship_type": "biomarker", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates HMGB1 release and inflammatory signaling.", "mechanism": "SIRT1-mediated downregulation of HMGB1 acetylation and glycosylation alleviates RA inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Immune inflammation", "glycan_involvement": "Altered glycosylation enhances IL-6 stability and receptor interaction.", "mechanism": "Glycosylation of IL-6 influences its secretion and pro-inflammatory activity in RA.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Synovitis", "glycan_involvement": "Glycosylation modulates TNFR1 receptor function.", "mechanism": "BIRC3/TNFR1 axis in FLS apoptosis/necroptosis; glycosylation affects TNFR1 signaling.", "protein": "TNFR1", "relationship_type": "causal", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Pyroptosis", "glycan_involvement": "Glycosylation regulates NLRP3 inflammasome activation.", "mechanism": "WTAP-mediated m6A modification and glycosylation of NLRP3 promote FLS pyroptosis and inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12262092" }, { "confidence": "medium", "disease": "Immune inflammation", "glycan_involvement": "Glycosylation modulates FCGR2B-mediated immune signaling.", "mechanism": "ACPA upregulates FCGR2B/IL-10 axis in macrophages; glycosylation affects FCGR2B function.", "protein": "FCGR2B", "relationship_type": "biomarker", "source_pmcid": "PMC12262092" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "TFRC is a transmembrane glycoprotein; glycosylation is essential for its stability and iron binding.", "mechanism": "TFRC mediates cellular iron uptake; its downregulation is linked to iron metabolism disturbance in HF.", "protein": "TFRC", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12263363" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation affects TFRC cell surface expression and function.", "mechanism": "TFRC downregulation suggests altered iron homeostasis in AF.", "protein": "TFRC", "relationship_type": "biomarker", "source_pmcid": "PMC12263363" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "CP is a heavily glycosylated secreted protein; glycosylation is critical for its stability and activity.", "mechanism": "CP is upregulated in HF; involved in iron and copper metabolism, correlates with increased mortality.", "protein": "CP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12263363" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation modulates CP secretion and function in plasma.", "mechanism": "CP upregulation is associated with increased AF risk and progression.", "protein": "CP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12263363" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Potential glycosylation may affect STEAP3 membrane localization and function.", "mechanism": "STEAP3 downregulation impairs iron/copper uptake, linked to negative regulation of cardiac hypertrophy.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12263363" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation status not directly discussed; possible impact on protein function.", "mechanism": "STEAP3 downregulation may contribute to iron metabolism disturbance in AF.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12263363" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "SAT1 involved in polyamine metabolism and ferroptosis regulation; diagnostic accuracy is high but qRT-PCR not significant.", "protein": "SAT1", "protein_enriched": { "function": "Enzyme which catalyzes the acetylation of polyamines (PubMed:15283699, PubMed:16455797, PubMed:17516632). Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine (PubMed:17", "gene_name": "SAT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P21673" }, "relationship_type": "biomarker", "source_pmcid": "PMC12263363" }, { "confidence": "low", "disease": "Atrial Fibrillation", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "SAT1 may regulate ferroptosis in AF; diagnostic accuracy high but qRT-PCR not significant.", "protein": "SAT1", "protein_enriched": { "function": "Enzyme which catalyzes the acetylation of polyamines (PubMed:15283699, PubMed:16455797, PubMed:17516632). Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine (PubMed:17", "gene_name": "SAT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P21673" }, "relationship_type": "biomarker", "source_pmcid": "PMC12263363" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "LPCAT3 downregulation affects membrane lipid composition and ferroptosis; diagnostic accuracy is low.", "protein": "LPCAT3", "protein_enriched": { "function": "Associates with SLC3A1/rBAT to form a functional heterodimeric complex that transports anionic and neutral amino acids across the apical plasma membrane of renal epithelium. Preferentially mediates ex", "gene_name": "SLC7A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TCU3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12263363" }, { "confidence": "low", "disease": "Atrial Fibrillation", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "LPCAT3 downregulation may impact ferroptosis in AF.", "protein": "LPCAT3", "protein_enriched": { "function": "Associates with SLC3A1/rBAT to form a functional heterodimeric complex that transports anionic and neutral amino acids across the apical plasma membrane of renal epithelium. Preferentially mediates ex", "gene_name": "SLC7A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TCU3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12263363" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "HMGCR is involved in dolichol-mediated glycoprotein synthesis, affecting glycosylation of muscle proteins.", "mechanism": "Biallelic pathogenic variants in HMGCR impair skeletal muscle development, leading to LGMD phenotype.", "protein": "HMG CoA reductase (HMGCR)", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "high", "disease": "Statin-associated myopathy (SAM)", "glycan_involvement": "Reduced mevalonate affects dolichol and glycoprotein synthesis in muscle.", "mechanism": "Statins inhibit HMGCR, leading to impaired muscle regeneration and increased apoptosis.", "protein": "HMG CoA reductase (HMGCR)", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "high", "disease": "Autoimmune anti-HMGCR myopathy", "glycan_involvement": "Glycosylation may affect antigenicity of HMGCR.", "mechanism": "Autoantibodies target HMGCR, causing necrotizing muscle disease.", "protein": "HMG CoA reductase (HMGCR)", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Impaired glycoprotein synthesis may affect membrane integrity.", "mechanism": "HMGCR deficiency or inhibition leads to muscle fiber breakdown and mitochondrial dysfunction.", "protein": "HMG CoA reductase (HMGCR)", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "medium", "disease": "Impaired myogenesis", "glycan_involvement": "Desmin glycosylation is altered, affecting filament assembly.", "mechanism": "Aberrant Des expression and glycosylation in HMGCR deficiency disrupts sarcomeric structure.", "protein": "Desmin (Des)", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "Des", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P31001" }, "relationship_type": "biomarker", "source_pmcid": "PMC12264025" }, { "confidence": "medium", "disease": "Muscular dystrophy with hearing loss and ovarian insufficiency", "glycan_involvement": "Geranylgeranyl pyrophosphate is required for glycoprotein modification.", "mechanism": "Variants in GGPS1 disrupt protein prenylation and glycoprotein synthesis, causing syndromic muscular dystrophy.", "protein": "GGPS1", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "medium", "disease": "Rigid spine syndrome", "glycan_involvement": "Reduced dolichol affects N-glycosylation of muscle proteins.", "mechanism": "Variants in HMGCS1 upstream of HMGCR impair mevalonate pathway and glycoprotein synthesis.", "protein": "HMGCS1", "relationship_type": "causal", "source_pmcid": "PMC12264025" }, { "confidence": "low", "disease": "Impaired myogenesis", "glycan_involvement": "Altered glycosylation may affect myosin function.", "mechanism": "Upregulation in HMGCR deficiency reflects compensatory changes in contractile apparatus.", "protein": "Myosin Light Chain 9 (Myl9)", "protein_enriched": { "function": "Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Implicated in cytokinesis, receptor capping,", "gene_name": "MYL9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24844" }, "relationship_type": "biomarker", "source_pmcid": "PMC12264025" }, { "confidence": "low", "disease": "Impaired myogenesis", "glycan_involvement": "Notch3 glycosylation modulates signaling.", "mechanism": "Upregulation in HMGCR deficiency may affect muscle cell fate decisions.", "protein": "Notch3", "relationship_type": "biomarker", "source_pmcid": "PMC12264025" }, { "confidence": "low", "disease": "Impaired myogenesis", "glycan_involvement": "Glycosylation affects Apelin secretion and activity.", "mechanism": "Downregulation in HMGCR deficiency may impair muscle regeneration.", "protein": "Apelin (Apln)", "protein_enriched": { "function": "Peptide hormone that functions as endogenous ligand for the G-protein-coupled apelin receptor (APLNR/APJ), that plays a role in cadiovascular homeostasis (PubMed:10525157, PubMed:22810587, PubMed:3581", "gene_name": "APLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ULZ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12264025" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation critical for laminin binding; hypoglycosylation impairs function in DMD.", "mechanism": "Serum fragments of alpha-dystroglycan reflect breakdown of the dystrophin-glycoprotein complex in DMD.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "high", "disease": "Myofibrosis", "glycan_involvement": "N- and O-glycosylation modulate ECM interactions and cell adhesion.", "mechanism": "Elevated serum fibronectin indicates ECM remodeling and fibrosis in dystrophic muscle.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "medium", "disease": "Myofibrosis", "glycan_involvement": "O-glycosylation affects cell signaling and immune modulation.", "mechanism": "Increased serum osteopontin reflects active fibrotic remodeling in DMD.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "high", "disease": "Myofibrosis", "glycan_involvement": "N- and O-glycosylation required for collagen stability and secretion.", "mechanism": "Serum collagen fragments are markers of ECM turnover and fibrosis in DMD.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "medium", "disease": "Myofibrosis", "glycan_involvement": "Glycosylation modulates secretion and activity of MMP-9.", "mechanism": "Elevated MMP-9 in serum reflects ECM degradation and remodeling in dystrophic muscle.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Defective O-glycosylation is a primary pathogenic mechanism.", "mechanism": "Loss of functional glycosylated alpha-dystroglycan disrupts sarcolemmal stability, contributing to DMD pathology.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12265423" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation may affect titin stability and proteolysis.", "mechanism": "Serum titin fragments indicate sarcomere breakdown in DMD.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential glycosylation may influence stability; not detailed in article.", "mechanism": "Serum MYOM3 reflects sarcomeric disintegration in DMD.", "protein": "Myomesin-3 (MYOM3)", "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation may affect protein folding and secretion.", "mechanism": "Serum MYBPC fragments are released upon muscle fiber damage in DMD.", "protein": "Myosin binding protein C", "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates fibronectin's ECM binding and function.", "mechanism": "Elevated serum fibronectin is a marker of ongoing muscle degeneration and ECM remodeling in DMD.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12265423" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin (AGE formation)", "mechanism": "HbA1c reflects chronic hyperglycemia and is associated with increased dermal oxygen saturation and altered skin microvasculature.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Atopic Dermatitis (AD)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "VEGF-driven neovascularization and hypervascularization in AD skin.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation modulates VEGF activity in angiogenesis.", "mechanism": "Diabetes induces VEGF expression, promoting aberrant microvascular remodeling.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12265499" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (DM)", "glycan_involvement": "Angiopoietins are glycoproteins; glycosylation influences vascular effects.", "mechanism": "Insulin stimulates Ang production, contributing to microvascular changes.", "protein": "Angiopoietin (Ang)", "protein_enriched": { "function": "Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, mi", "gene_name": "ANGPT1", "glycan_count": 7, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G41071NU", "G49906RN", "G62765YT", "G80920RR", "G90659AW", "G57321FI" ], "uniprot_id": "Q15389" }, "relationship_type": "causal", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Diabetic Microangiopathy", "glycan_involvement": "Glycation of serum proteins forms AGEs.", "mechanism": "AGEs cause endothelial dysfunction, vessel necrosis, and aberrant angiogenesis.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Atopic Dermatitis (AD)", "glycan_involvement": "Ceramide is a glycosphingolipid; glycan moiety essential for barrier function.", "mechanism": "Low ceramide levels indicate impaired skin barrier and increased TEWL in AD.", "protein": "Ceramide", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12265499" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (DM)", "glycan_involvement": "Altered sphingolipid metabolism affects glycan composition.", "mechanism": "Diabetes is associated with reduced epidermal ceramide, reflecting impaired barrier.", "protein": "Ceramide", "relationship_type": "biomarker", "source_pmcid": "PMC12265499" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (DM)", "glycan_involvement": "Uric acid supports keratinocyte differentiation via glycoproteins (filaggrin, loricrin).", "mechanism": "Reduced uric acid in diabetic skin correlates with increased xerosis and AD risk.", "protein": "Uric Acid", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Atopic Dermatitis (AD)", "glycan_involvement": "Filaggrin is glycosylated; glycosylation affects barrier function.", "mechanism": "Filaggrin deficiency impairs skin barrier, predisposing to AD.", "protein": "Filaggrin", "protein_enriched": { "function": "Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis", "gene_name": "FLG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20930" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12265499" }, { "confidence": "medium", "disease": "Skin Xerosis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Reduced transglutaminase-1 activity impairs keratinocyte differentiation and moisture retention.", "protein": "Transglutaminase-1", "protein_enriched": { "function": "Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross-linking epidermal proteins during formation of the stratum corneum. Involved in cell prolif", "gene_name": "TGM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P22735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12265499" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-glycosylation mediates binding and decoy function.", "mechanism": "Acts as a steric hindrance and releasable decoy for H. pylori binding, reducing colonization.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "protective", "source_pmcid": "PMC12269685" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-glycosylation critical for pathogen binding.", "mechanism": "Binds H. pylori, regulates growth and virulence, removal from gastric niche.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "protective", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Secreted with MUC5AC, involved in mucin assembly.", "mechanism": "Binds H. pylori, slows movement in mucus, promotes mucosal healing.", "protein": "TFF1", "relationship_type": "protective", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "Altered O-glycosylation affects barrier function.", "mechanism": "Loss or alteration increases risk of cancer due to impaired barrier.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "O-glycosylation changes impact mucosal protection.", "mechanism": "Reduced mucin production linked to increased cancer risk.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation may affect peptide stability.", "mechanism": "Upregulated after infection, contributes to mucosal defense.", "protein": "Defensin \u03b21 (Defb1)", "protein_enriched": { "function": "Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), ", "gene_name": "Gria2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P23819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation modulates antimicrobial function.", "mechanism": "Upregulated in infected patients, antimicrobial activity.", "protein": "Lactoferrin (Ltf)", "protein_enriched": { "function": "Component of innate and adaptive immunity that recognizes and binds 23S rRNA from bacteria. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular p", "gene_name": "Tlr13", "glycan_count": 6, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G80920RR", "G02815KT", "G26436YP", "G41247ZX", "G83460ZZ", "G28541PG" ], "uniprot_id": "Q6R5N8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation affects inhibitory activity.", "mechanism": "Decreased in infected patients, loss may impair defense.", "protein": "Secretory Leukocyte Peptidase Inhibitor (Slpi)", "protein_enriched": { "function": "Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:9126337). Modulates the innate immune response after bacterial infection (PubMed:12", "gene_name": "Slpi", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P97430" }, "relationship_type": "biomarker", "source_pmcid": "PMC12269685" }, { "confidence": "medium", "disease": "Peptic ulcer disease", "glycan_involvement": "O-glycosylation essential for barrier function.", "mechanism": "Decreased mucin production impairs barrier, increasing ulcer risk.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12269685" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-glycosylation and sialylation modulate pathogen interactions.", "mechanism": "Restoring mucin production (via IL4 or R\u03b1MH) reduces H. pylori density.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12269685" }, { "confidence": "high", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "A1BG is a glycoprotein; glycosylation may affect its stability and immune-modulatory function.", "mechanism": "Serum A1BG levels are significantly decreased in dogs with BPH; levels normalize after castration, reflecting disease resolution.", "protein": "Alpha-1B glycoprotein (A1BG)", "relationship_type": "biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation likely influences A1BG's immune-modulatory properties.", "mechanism": "A1BG may modulate local immune responses during chronic prostatic inflammation in BPH.", "protein": "Alpha-1B glycoprotein (A1BG)", "relationship_type": "biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "high", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "Glycosylation may affect A1BG's serum stability and detectability.", "mechanism": "Normalization of A1BG post-castration indicates therapeutic efficacy and disease resolution.", "protein": "Alpha-1B glycoprotein (A1BG)", "relationship_type": "therapeutic monitoring", "source_pmcid": "PMC12269933" }, { "confidence": "medium", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "Age-related changes in glycosylation may influence A1BG levels.", "mechanism": "A1BG levels inversely correlate with age in BPH-affected dogs, possibly reflecting inflammaging.", "protein": "Alpha-1B glycoprotein (A1BG)", "relationship_type": "age-related biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "high", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "CRP is a glycoprotein; glycosylation is essential for its function but not specifically altered in BPH.", "mechanism": "Serum CRP levels do not differ between BPH and controls, indicating limited diagnostic value for localized prostatic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation is required for CRP's acute-phase activity.", "mechanism": "Elevated CRP is associated with poor prognosis in prostate cancer, but not in BPH.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may modulate A1BG's disease association.", "mechanism": "A1BG may be involved in prostatic disease pathophysiology, but its role in cancer is not established in this study.", "protein": "Alpha-1B glycoprotein (A1BG)", "relationship_type": "potential biomarker", "source_pmcid": "PMC12269933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation at Asn467/496 modulates APP processing.", "mechanism": "Aberrant N-glycosylation at Asn467 and Asn496 alters APP trafficking and cleavage, increasing A\u03b2 production and amyloid plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12270687" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-GlcNAcylation at Ser400, Thr403/404 protects against tau hyperphosphorylation.", "mechanism": "Reduced O-GlcNAcylation increases tau phosphorylation and aggregation, promoting neurofibrillary tangle formation.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12270687" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates BACE1 enzymatic activity.", "mechanism": "Altered N-glycosylation increases BACE1 activity, elevating A\u03b2 levels.", "protein": "Beta-secretase 1 (BACE1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12270687" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation and citrullination affect A\u03b2 aggregation and toxicity.", "mechanism": "O-glycosylation (Tyr10, Tyr681) and citrullination promote aggregation and neurotoxicity.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation (fucosylation) status serves as a biomarker.", "mechanism": "Decreased fucosylation of CN1 in CSF correlates with AD.", "protein": "Carnosinase CN1", "protein_enriched": { "function": "Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides, displaying the highest activity toward carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-3-methyl-histidine)", "gene_name": "CNDP1", "glycan_count": 24, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G45395BF", "G00912UN", "G06247RL", "G11629QQ", "G12341GU", "G15169WU", "G22310AV", "G29511JR", "G33791AF", "G37881RL", "G43089EG", "G47518TP", "G47748JZ", "G48414YA", "G52131KU", "G52527GH", "G55412XP", "G56784JY", "G70232NH", "G70888PK", "G75983OB", "G81124ET", "G84452RH" ], "uniprot_id": "Q96KN2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation profile changes in AD.", "mechanism": "Altered N-glycosylation microheterogeneity detected in AD CSF.", "protein": "Alpha-1-antichymotrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation microheterogeneity as a biomarker.", "mechanism": "Site-specific N-glycosylation changes in CSF distinguish AD from controls.", "protein": "Ephrin-A3", "protein_enriched": { "function": "Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Bin", "gene_name": "EFNA3", "glycan_count": 15, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02030ZB", "G02628JF", "G25451PN", "G60177UT", "G64527OM", "G70101JE", "G75983OB", "G78790NZ", "G82830MN", "G83229XP", "G84452RH", "G86182NS", "G92062TF", "G95977AE", "G08290VR" ], "uniprot_id": "P52797" }, "relationship_type": "biomarker", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Down-regulation of N-glycosylation in AD mouse models may affect synaptic function.", "protein": "Glutamate receptors", "relationship_type": "causal", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Citrullination (not classical glycosylation) alters protein charge and aggregation.", "mechanism": "Abnormal accumulation of citrullinated vimentin in AD brain regions.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "causal", "source_pmcid": "PMC12270687" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Citrullination affects protein stability and immune response.", "mechanism": "Abnormal accumulation of citrullinated GFAP in hippocampus and cortex of AD patients.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "causal", "source_pmcid": "PMC12270687" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "N-glycosylation at Asn-42/Asn-68 modulates ligand binding and oligomerization, affecting cytotoxic function.", "mechanism": "NKp30 activation enhances NK cell cytotoxicity against tumor cells via ligand binding (notably B7-H6); downregulation impairs antitumor immunity.", "protein": "NKp30", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "B7-H6 is a glycoprotein; glycosylation status not detailed for function.", "mechanism": "B7-H6 is selectively expressed on tumor cells, activates NKp30-mediated cytotoxicity; soluble B7-H6 can downregulate NKp30 and impair NK function.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "N-glycosylation required for ligand binding and function.", "mechanism": "Decreased NKp30 expression correlates with impaired NK cytolytic function and poor viral control; engagement on V\u03b41 T cells induces chemokines inhibiting HIV replication.", "protein": "NKp30", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12272517" }, { "confidence": "high", "disease": "Hepatitis B/C virus infection", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "NKp30 upregulation correlates with better viral control and treatment response; isoform balance affects fibrosis/cirrhosis.", "protein": "NKp30", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "N-glycosylation required for ligand recognition.", "mechanism": "NKp30 binds PfEMP-1 on infected RBCs, triggers NK cytotoxicity and parasite clearance.", "protein": "NKp30", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Cryptococcosis", "glycan_involvement": "N-glycosylation required for synapse formation and function.", "mechanism": "NKp30 mediates NK cell recognition and killing of Cryptococcus neoformans via perforin and PI3K/ERK1/2 signaling.", "protein": "NKp30", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Primary Sj\u00f6gren's syndrome", "glycan_involvement": "N-glycosylation required for ligand interaction.", "mechanism": "NKp30/B7-H6 axis in salivary glands drives NK cell cytotoxicity and inflammation; genetic variants reducing NKp30 are protective.", "protein": "NKp30", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Antisynthetase syndrome", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Reduced NKp30 expression on NK cells correlates with impaired IFN-\u03b3 production and NK cell dysfunction.", "protein": "NKp30", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Gal-3 is a glycoprotein; glycan-binding activity mediates inhibition.", "mechanism": "Soluble Gal-3 from tumor cells binds NKp30, inhibits NKp30-mediated cytotoxicity, promoting tumor immune evasion.", "protein": "Galectin-3 (Gal-3)", "relationship_type": "causal", "source_pmcid": "PMC12272517" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "BAG6 is a glycoprotein; glycosylation not detailed for function.", "mechanism": "Tumor-derived BAG6 binds NKp30, promotes NK cell cytotoxicity and antitumor immunity.", "protein": "BAG6 (BAT3)", "protein_enriched": { "function": "ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control comp", "gene_name": "BAG6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P46379" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12272517" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Upregulation of sialyl core-2 O-glycans on tumor cells", "mechanism": "Increased expression detected in invasive ductal carcinoma compared to normal tissue", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Enhanced sialyl core-2 O-glycan expression on cancer cell surface", "mechanism": "High binding of sCore2 to highly metastatic COLO357-FG cells", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "high", "disease": "Solid tumors (e.g., kidney, uterine, prostate, colon carcinoma)", "glycan_involvement": "Increased core-2 O-glycan branching via GCNT1 activity", "mechanism": "GCNT1 upregulated in multiple TCGA cancers; drives core-2 O-glycan branching", "protein": "GCNT1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12274613" }, { "confidence": "medium", "disease": "Myelodysplastic neoplasms", "glycan_involvement": "Changes in sialyl core-2 O-glycan levels on blood cells", "mechanism": "Altered cell-surface carbohydrates detected in these hematologic malignancies", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "high", "disease": "Immune cell differentiation", "glycan_involvement": "Acquisition of sialyl core-2 O-glycans during lymphocyte differentiation", "mechanism": "sCore2 binding increases with T and NK cell maturation; reflects glycan remodeling", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Presence of sialyl core-2 O-glycans on infiltrating immune cells", "mechanism": "Detected on inflammatory cells in liver tissue", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Aberrant expression of sialyl core-2 O-glycans in tumors", "mechanism": "Detected in various tumor tissues and not in most normal tissues", "protein": "Sialyl core-2 O-glycan", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "high", "disease": "Cell differentiation", "glycan_involvement": "Drives core-2 O-glycan branching during immune cell development", "mechanism": "GCNT1 expression correlates with T cell maturation and sialyl core-2 O-glycan levels", "protein": "GCNT1", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "medium", "disease": "Metabolic disorders", "glycan_involvement": "ST3Gal1-mediated sialylation of core-2 O-glycans", "mechanism": "Altered glycosylation patterns (including sialyl core-2) accompany metabolic disease", "protein": "ST3Gal1", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "medium", "disease": "Hematologic malignancies", "glycan_involvement": "CD43 carries core-2 O-glycans in hematopoietic cells", "mechanism": "Anti-CD43 antibody (1B11) recognizes core-2 O-glycans on blood cells", "protein": "CD43", "relationship_type": "biomarker", "source_pmcid": "PMC12274613" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycosylated proteins in the dystrophin-glycoprotein complex, crucial for membrane stability.", "mechanism": "Loss-of-function mutations in dystrophin gene cause deficiency, leading to muscle membrane instability and progressive muscle wasting.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12278061" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of complex components is essential for function and membrane anchoring.", "mechanism": "Defective dystrophin impairs the glycoprotein complex, disrupting cell signaling and membrane stability in cardiac muscle, leading to cardiomyopathy.", "protein": "Dystrophin-Glycoprotein Complex", "relationship_type": "causal", "source_pmcid": "PMC12278061" }, { "confidence": "medium", "disease": "Arrhythmia (ventricular tachycardia)", "glycan_involvement": "Indirect; glycosylation of associated proteins affects complex stability.", "mechanism": "Dystrophin deficiency increases vulnerability to arrhythmias due to membrane instability and abnormal calcium handling.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12278061" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Troponin T is glycosylated, which may affect its release and detection.", "mechanism": "Elevated troponin T levels indicate cardiac muscle injury in MDCs, especially with CMR evidence of fibrosis.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC12278061" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Troponin I glycosylation may influence serum levels.", "mechanism": "Elevated troponin I levels serve as a marker for cardiac involvement in MDCs.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12278061" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Not a glycoprotein; included for context.", "mechanism": "Elevated CK reflects muscle membrane instability and ongoing muscle damage in dystrophinopathies.", "protein": "Creatine Kinase (CK)", "relationship_type": "biomarker", "source_pmcid": "PMC12278061" }, { "confidence": "high", "disease": "Becker Muscular Dystrophy (BMD)", "glycan_involvement": "Glycosylation of associated complex proteins modulates severity.", "mechanism": "In-frame mutations produce partially functional dystrophin, resulting in milder disease.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12278061" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation is critical for complex integrity and cardiac muscle function.", "mechanism": "Disruption of the complex leads to progressive cardiac dysfunction and heart failure in MDCs.", "protein": "Dystrophin-Glycoprotein Complex", "relationship_type": "causal", "source_pmcid": "PMC12278061" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "NTproBNP is glycosylated, affecting its stability and detection.", "mechanism": "NTproBNP levels reflect cardiac stress and are used to monitor heart failure risk.", "protein": "NTproBNP", "relationship_type": "biomarker", "source_pmcid": "PMC12278061" }, { "confidence": "low", "disease": "Myocarditis", "glycan_involvement": "Indirect; glycosylation of interacting proteins may modulate immune response.", "mechanism": "Dystrophin deficiency may increase susceptibility to myocardial injury and inflammation.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "risk modifier", "source_pmcid": "PMC12278061" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "HA is a viral glycoprotein; glycosylation affects immune evasion and receptor binding.", "mechanism": "Palmitoylation of HA enhances membrane fusion and interaction with M1 matrix protein, promoting viral entry and assembly.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "S protein is heavily glycosylated; glycosylation modulates immune recognition and entry.", "mechanism": "Rapid S-palmitoylation of S protein by ZDHHC20/9 is essential for viral replication and infectivity.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "E protein is glycosylated; glycosylation may affect assembly and immune response.", "mechanism": "Palmitoylation at C40, C43, C44 stabilizes E protein and promotes assembly with other viral proteins.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome virus (PRRSV)", "glycan_involvement": "GP5 is a viral glycoprotein; glycosylation affects virion assembly and immune evasion.", "mechanism": "N-terminal acetylation by NAT9 promotes K27-linked ubiquitination and degradation, reducing viral particle assembly.", "protein": "Glycoprotein 5 (GP5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "ACE2 is a host glycoprotein; glycosylation modulates spike binding and viral entry.", "mechanism": "Palmitoylation at Cys141/498 facilitates ACE2 secretion in extracellular vesicles, capturing virus and preventing cell entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "protective", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "IFITM3 is a glycoprotein; glycosylation may affect trafficking and function.", "mechanism": "Palmitoylation maintains IFITM3 stability and localization, enhancing antiviral activity by blocking viral entry.", "protein": "IFITM3", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P14210" }, "relationship_type": "protective", "source_pmcid": "PMC12279274" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "PLSCR2 is glycosylated; glycosylation may affect protein-protein interactions.", "mechanism": "Palmitoylated PLSCR2 interacts with STAT3, suppressing ISGF3-mediated transcription and dampening antiviral response.", "protein": "PLSCR2", "relationship_type": "biomarker", "source_pmcid": "PMC12279274" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "NP is not a glycoprotein; no direct glycan involvement.", "mechanism": "Succinylation at K87 alters NP charge, promoting nuclear retention and disrupting viral assembly.", "protein": "Nucleocapsid protein (NP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "medium", "disease": "Japanese encephalitis virus (JEV)", "glycan_involvement": "NS2A is not a glycoprotein; no direct glycan involvement.", "mechanism": "Palmitoylation at C221 enhances NS2A stability, boosting replication efficiency and virulence.", "protein": "NS2A", "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "medium", "disease": "Hepatitis C virus (HCV)", "glycan_involvement": "NS2 is not a glycoprotein; no direct glycan involvement.", "mechanism": "Palmitoylation at C113 is critical for RNA replication by promoting NS2-NS3 precursor autoprocessing.", "protein": "NS2", "protein_enriched": { "function": "", "gene_name": "NS5b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O39930" }, "relationship_type": "causal", "source_pmcid": "PMC12279274" }, { "confidence": "high", "disease": "Frailty", "glycan_involvement": "AGP is heavily N-glycosylated; glycosylation modulates its anti-inflammatory properties and half-life.", "mechanism": "AGP reflects chronic low-grade inflammation, which is a central pathway in frailty development.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Altered glycosylation patterns of AGP may affect its interaction with immune cells.", "mechanism": "Elevated AGP levels are associated with increased cardiovascular risk due to chronic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Malignancies", "glycan_involvement": "Cancer alters AGP glycosylation, affecting immune modulation.", "mechanism": "AGP levels rise in response to tumor-associated inflammation and tissue injury.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation may influence AGP's anti-inflammatory activity.", "mechanism": "AGP is elevated in hypertension, reflecting underlying inflammatory processes.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Liver disease alters AGP glycosylation, impacting its function.", "mechanism": "AGP is synthesized by the liver; levels increase in cirrhosis due to hepatic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation changes in AGP modulate immune cell interactions.", "mechanism": "AGP is upregulated in rheumatoid arthritis as part of the acute-phase response.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Diabetes may alter AGP glycosylation, affecting its anti-inflammatory properties.", "mechanism": "AGP levels are increased in diabetes, reflecting systemic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12280186" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Heavily N-glycosylated, especially at N180, N339, N386; glycosylation enhances metastatic function.", "mechanism": "Promotes cell migration and metastasis via EV-mediated transfer and activation of SRC/JUN signaling.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation status increases in metastatic cells/EVs.", "mechanism": "High CDCP1 expression correlates with poor prognosis in LUAD and LUSC patients.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12281461" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation at N339 and N386 are critical for function.", "mechanism": "Knockout of CDCP1 reduces cell migration and metastatic signaling.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12281461" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Detected only in high metastatic EVs with multiple N-glycosylation sites.", "mechanism": "Upregulated and hyperglycosylated in metastatic EVs; may promote cell migration.", "protein": "TNC", "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Increased N-glycosylation in high metastatic EVs.", "mechanism": "Upregulated in metastatic EVs; involved in cell adhesion/migration.", "protein": "NCAM2", "protein_enriched": { "function": "Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting (PubMed:17646382). Sorting rec", "gene_name": "SORL1", "glycan_count": 99, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G00912UN", "G07246CJ", "G08290VR", "G08918WF", "G11870QZ", "G25418HZ", "G25451PN", "G27058EU", "G34989PA", "G37412TK", "G41071NU", "G43223CG", "G45395BF", "G47644PP", "G50856PC", "G57776ZS", "G59626AS", "G61256FT", "G62765YT", "G70232NH", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81263BG", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G92135MA", "G93718GY", "G96577RX", "G57321FI", "G29068FM", "G43417UB", "G04657PL", "G35253PZ", "G80920RR", "G83460ZZ", "G86182NS", "G95865ZB", "G53434XO", "G31852PQ", "G64409MC", "G83229XP", "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G39188ZX", "G64527OM", "G70101JE", "G01485JJ", "G07755XJ", "G10488MI", "G14972EH", "G17208MA", "G42124LM", "G58954YZ", "G70619PT", "G87661QW", "G92551JA", "G94470IW", "G49108TO", "G41247ZX", "G34029GR", "G46503DX", "G48584BU", "G85677PP", "G96368MM", "G10486CT", "G00273SJ", "G05049YU", "G27915IV", "G95177YH", "G37692EO", "G37399XV", "G40926MX", "G45504EY", "G83646BJ", "G11314AS", "G49955PK", "G72790NZ", "G10819WX", "G27947YN", "G29545VG", "G44215PV", "G59324HL", "G60033FS", "G63980BQ", "G65184UU", "G85269DF", "G90734RJ", "G98611JV", "G06247RL", "G20706XG", "G43669FQ" ], "uniprot_id": "Q92673" }, "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Increased N-glycosylation in high metastatic EVs.", "mechanism": "Upregulated in metastatic EVs; involved in cell adhesion/migration.", "protein": "ITGA4", "protein_enriched": { "function": "Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are al", "gene_name": "ITGA4", "glycan_count": 25, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G15664MX", "G23505EP", "G27058EU", "G31852PQ", "G41071NU", "G42124LM", "G43223CG", "G62765YT", "G80920RR", "G83460ZZ", "G90659AW", "G02815KT", "G11314AS", "G35253PZ", "G41247ZX", "G58087IP", "G81315DD", "G39471UU", "G76868JS", "G85554PZ", "G16125XL", "G82501QM", "G57776ZS", "G45395BF", "G63041LO" ], "uniprot_id": "P13612" }, "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Indirect; downstream of CDCP1 glycosylation.", "mechanism": "Phosphorylation of SRC is reduced upon CDCP1 knockout, impairing metastatic signaling.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Indirect; downstream of CDCP1 glycosylation.", "mechanism": "Phosphorylation of JUN is reduced upon CDCP1 knockout, impairing metastatic signaling.", "protein": "JUN", "protein_enriched": { "function": "Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcri", "gene_name": "JUN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P05412" }, "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation required for EV surface localization.", "mechanism": "Defines subpopulation of cancer-derived EVs; involved in tumor progression.", "protein": "CD147", "protein_enriched": { "function": "Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photor", "gene_name": "BSG", "glycan_count": 62, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G49108TO", "G01160VV", "G02815KT", "G05049YU", "G08918WF", "G10488MI", "G15127JD", "G15664MX", "G23719VF", "G27058EU", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G50856PC", "G53075ES", "G57776ZS", "G59626AS", "G62765YT", "G65414LI", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G74381CZ", "G77330BQ", "G79666IR", "G80075MS", "G80920RR", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G29068FM", "G43417UB", "G05724UK", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G20210JR", "G20528HD", "G23294PN", "G28681TP", "G32788FZ", "G35541EV", "G46275YY", "G47644PP", "G49755GI", "G60967DT", "G64527OM", "G70101JE", "G70619PT", "G80479JV", "G83460ZZ", "G85269DF", "G92062TF", "G93718GY", "G50713DU" ], "uniprot_id": "P35613" }, "relationship_type": "biomarker", "source_pmcid": "PMC12281461" }, { "confidence": "low", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation status not specified.", "mechanism": "Downregulated in CDCP1 KO cells; associated with cell migration.", "protein": "MME", "relationship_type": "causal", "source_pmcid": "PMC12281461" }, { "confidence": "high", "disease": "HHV-6 infection", "glycan_involvement": "CD317 is a glycosylated protein; glycosylation is essential for its antiviral function.", "mechanism": "Restricts HHV-6 infection by inhibiting viral entry and promoting degradation of viral glycoprotein gO.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "medium", "disease": "Exanthem subitum (roseola infantum)", "glycan_involvement": "Glycosylation of CD317 required for membrane localization and function.", "mechanism": "Limits HHV-6 infection, the causative agent of roseola, by restricting viral entry.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "low", "disease": "Lymphoproliferative disorders", "glycan_involvement": "Glycosylation status affects antiviral activity.", "mechanism": "Induced during HHV-6 infection, which is associated with lymphoproliferative disorders.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "medium", "disease": "HCMV infection", "glycan_involvement": "Glycosylation may modulate interaction with viral glycoproteins.", "mechanism": "Promotes HCMV infection at the entry stage (contrary to its restriction of other viruses).", "protein": "CD317", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "HSV-1 infection", "glycan_involvement": "Glycosylation required for antiviral tethering function.", "mechanism": "Restricts HSV-1 release from infected cells.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "HSV-2 infection", "glycan_involvement": "Glycosylation required for antiviral function.", "mechanism": "Restricts HSV-2 release from infected cells.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "KSHV infection", "glycan_involvement": "Glycosylation required for antiviral function.", "mechanism": "Restricts KSHV release from infected cells.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation required for membrane tethering.", "mechanism": "Restricts release of SARS-CoV-2 virions from infected cells.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation required for antiviral function.", "mechanism": "Restricts release of HIV-1 and HIV-2 virions from infected cells.", "protein": "CD317", "relationship_type": "protective", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "HHV-6 infection", "glycan_involvement": "gO is a viral glycoprotein; glycosylation likely affects its stability and interaction with CD317.", "mechanism": "gO is targeted by CD317 for proteasomal degradation, reducing viral entry and infectivity.", "protein": "HHV-6 gO", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12282140" }, { "confidence": "high", "disease": "Lassa fever", "glycan_involvement": "Glycosylation of GPC is essential for proper folding, immune evasion, and receptor binding.", "mechanism": "GPC mediates viral entry into host cells, initiating infection and disease.", "protein": "Lassa virus glycoprotein complex (GPC)", "protein_enriched": { "function": "Capsid protein. Probably binds RNA and plays a role in packaging", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JPX0" }, "relationship_type": "causal", "source_pmcid": "PMC12282416" }, { "confidence": "high", "disease": "Lassa fever", "glycan_involvement": "Glycosylation sites on GPC influence inhibitor binding and efficacy.", "mechanism": "LHF-535 inhibits GPC-mediated viral entry, reducing viral replication and disease severity.", "protein": "Lassa virus glycoprotein complex (GPC)", "protein_enriched": { "function": "Capsid protein. Probably binds RNA and plays a role in packaging", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JPX0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12282416" }, { "confidence": "high", "disease": "PGM3 deficiency (Congenital Disorder of Glycosylation)", "glycan_involvement": "Defective N- and O-glycosylation, proteoglycan, and GPI-anchor biosynthesis.", "mechanism": "Loss-of-function mutations in PGM3 disrupt UDP-GlcNAc synthesis, impairing multiple glycosylation pathways.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "Hyper-IgE Syndrome (HIES)-like phenotype", "glycan_involvement": "Altered glycosylation of TCR and CD28 affects T cell activation and subset differentiation.", "mechanism": "PGM3 mutations lead to Th2 polarization, elevated IgE, and atopy due to impaired glycosylation of immune receptors.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "Combined Immunodeficiency (CID)", "glycan_involvement": "Defective glycosylation of immune cell surface proteins.", "mechanism": "PGM3 deficiency impairs T cell development and function, reducing immune competence.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "Severe Combined Immunodeficiency (SCID)", "glycan_involvement": "Near-complete loss of N- and O-glycosylation in immune cells.", "mechanism": "Severe loss of PGM3 function leads to near-absent glycosylation, causing profound lymphopenia.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "medium", "disease": "Chronic Neutropenia", "glycan_involvement": "Impaired glycosylation affects neutrophil maturation.", "mechanism": "PGM3 deficiency disrupts leukocyte development and maturation.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "Eczema/Atopic Dermatitis", "glycan_involvement": "Altered glycosylation of immune receptors and skin proteins.", "mechanism": "PGM3 deficiency promotes Th2 immune responses and atopy.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder / Cognitive Delay", "glycan_involvement": "Defective glycosylation of neural proteins and signaling molecules.", "mechanism": "PGM3 deficiency affects glycosylation in neural development.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome", "glycan_involvement": "Impaired glycosylation may affect hematopoietic stem cell function.", "mechanism": "PGM3 pathogenic variants increase risk for hematological malignancy.", "protein": "Phosphoglucomutase 3 (PGM3)", "protein_enriched": { "function": "May increase cell susceptibility to TNF-induced apoptosis", "gene_name": "PPP1R1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WVI7" }, "relationship_type": "risk factor", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "PGM3 deficiency (Congenital Disorder of Glycosylation)", "glycan_involvement": "N- and O-glycosylation of TCR required for function.", "mechanism": "Defective glycosylation of TCR impairs T cell activation and proliferation.", "protein": "T-cell receptor (TCR)", "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "high", "disease": "PGM3 deficiency (Congenital Disorder of Glycosylation)", "glycan_involvement": "N-glycosylation of CD28 necessary for signaling.", "mechanism": "Impaired glycosylation of CD28 compromises co-stimulation of T cells.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC12282493" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Fab N-glycosylation (including sialylation, bisection, sulfation) modulates antibody function.", "mechanism": "Altered Fab N-glycosylation affects antigen binding and immune regulation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12283335" }, { "confidence": "medium", "disease": "B cell malignancies", "glycan_involvement": "Fab N-glycans (including sulfation, bisecting LacNAc) are altered in malignancy.", "mechanism": "Fab N-glycosylation patterns are associated with B cell malignancy status.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12283335" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Fc N-glycosylation regulates complement activation and cell-mediated cytotoxicity.", "mechanism": "Fc N-glycan features (fucosylation, galactosylation, sialylation) modulate effector functions and inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12283335" }, { "confidence": "low", "disease": "Viral infections", "glycan_involvement": "Sulfated and sialylated N-glycans may affect viral binding and immune evasion.", "mechanism": "IgG N-glycosylation influences antibody-virus interactions and immune response.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12283335" }, { "confidence": "medium", "disease": "Congenital disorder of glycosylation type IIa", "glycan_involvement": "Bisecting LacNAc motif on N-glycans is a disease marker.", "mechanism": "Presence of bisecting LacNAc on hybrid-type N-glycans is characteristic of this disorder.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC12283335" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Sialylated and sulfated N-glycans on Fab regulate BCR-CD22 interaction.", "mechanism": "Fab N-glycosylation modulates BCR signaling and antigen binding, affecting autoimmunity.", "protein": "B cell receptor (BCR)", "relationship_type": "causal", "source_pmcid": "PMC12283335" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "\u03b12-6-sialylated 6-sulfo-LacNAc motif on Fab binds CD22, influencing B cell activity.", "mechanism": "Sulfated Fab N-glycans may modulate B cell activation via CD22 binding.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12283335" }, { "confidence": "low", "disease": "B cell malignancies", "glycan_involvement": "Fab N-glycan sulfation/bisection may modulate cell interactions.", "mechanism": "Altered Fab glycosylation (including sulfation) may affect B cell signaling and malignancy progression.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12283335" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Fc glycan engineering (fucosylation, sialylation) alters therapeutic antibody activity.", "mechanism": "Fc N-glycan modifications are targeted to modulate antibody effector functions in therapy.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12283335" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Increased Fab glycosylation (including sulfation, bisecting LacNAc) observed in autoimmunity.", "mechanism": "Fab glycosylation frequency and structure (including rare modifications) are altered in disease.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12283335" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 glycosylation affects its stability and immune evasion.", "mechanism": "High PD-L1 expression predicts response to pembrolizumab immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12283722" }, { "confidence": "high", "disease": "Immunoresistance", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and impairs T cell recognition.", "mechanism": "Glycosylated PD-L1 mediates immune escape, contributing to resistance to immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12283722" }, { "confidence": "medium", "disease": "Brain metastases (BM)", "glycan_involvement": "TIMP1 is a glycoprotein; glycosylation may affect its secretion and activity.", "mechanism": "STAT3-driven TIMP1 secretion by reactive astrocytes promotes immunosuppression in BM.", "protein": "TIMP1", "relationship_type": "causal", "source_pmcid": "PMC12283722" }, { "confidence": "medium", "disease": "METex14 skipping mutated NSCLC", "glycan_involvement": "MET is glycosylated; glycosylation affects receptor function and signaling.", "mechanism": "METex14 mutation is associated with high PD-L1 and immune infiltration, influencing therapy response.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12283722" }, { "confidence": "low", "disease": "Brain metastases (BM)", "glycan_involvement": "CD63 is a glycoprotein; glycosylation may affect cell-cell interactions.", "mechanism": "CD63+ CD8+ T cells modulated by TIMP1 in the BM microenvironment.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12283722" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "EGFR glycosylation modulates receptor activation and ligand binding.", "mechanism": "EGFR signaling promotes tumor growth and metastasis; silibinin inhibits EGFR downstream pathways.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12283722" }, { "confidence": "high", "disease": "Brain metastases (BM)", "glycan_involvement": "Inhibition of N-glycosylation leads to mannose-rich PD-L1, increasing immune recognition.", "mechanism": "Silibinin blocks PD-L1 maturation during glycosylation, enhancing immunotherapy efficacy in BM.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12283722" }, { "confidence": "medium", "disease": "Immunoresistance", "glycan_involvement": "Glycosylation may regulate TIMP1 stability and immunomodulatory activity.", "mechanism": "TIMP1 secretion by astrocytes suppresses immune cell function, contributing to resistance.", "protein": "TIMP1", "relationship_type": "causal", "source_pmcid": "PMC12283722" }, { "confidence": "medium", "disease": "METex14 skipping mutated NSCLC", "glycan_involvement": "Glycosylation status may influence PD-L1 detection and function.", "mechanism": "High PD-L1 expression is characteristic of METex14 NSCLC and predicts immunotherapy response.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12283722" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Altered glycosylation (mannose-rich PD-L1) increases immunogenicity.", "mechanism": "Silibinin-induced glycosylation changes sensitize PD-L1 to dimer-inducing drugs and T-cell attack.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12283722" }, { "confidence": "high", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "SGLT2 inhibitors reduce mortality and morbidity in HFrEF by promoting glycosuria and improving cardiac and renal outcomes.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "ACE is glycosylated; glycosylation modulates enzymatic activity and stability.", "mechanism": "ACE inhibitors reduce afterload and neurohormonal activation, improving survival in HFrEF.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "AGTR1 glycosylation affects receptor trafficking and ligand binding.", "mechanism": "ARBs block angiotensin II signaling, reducing vasoconstriction and cardiac remodeling.", "protein": "Angiotensin II receptor type 1 (AGTR1)", "protein_enriched": { "function": "Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney (PubMed:15611106, PubMed:1567413, PubMed:25913193, PubMed:26", "gene_name": "AGTR1", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G12261QD", "G62765YT", "G84225JN" ], "uniprot_id": "P30556" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "Glycosylation of beta-adrenergic receptors influences receptor stability and signaling.", "mechanism": "Beta-blockers inhibit sympathetic overactivation, reducing mortality and hospitalization.", "protein": "Beta-adrenergic receptor (ADRB1/ADRB2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "medium", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "NR3C2 is glycosylated; glycosylation may affect receptor function.", "mechanism": "MRAs block aldosterone effects, reducing fibrosis and improving outcomes in HFrEF.", "protein": "Mineralocorticoid receptor (NR3C2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "medium", "disease": "Heart failure with reduced ejection fraction (HFrEF)", "glycan_involvement": "Neprilysin glycosylation is important for enzymatic activity.", "mechanism": "ARNi (neprilysin inhibitors) increase natriuretic peptides, reducing cardiac stress.", "protein": "Neprilysin (MME)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "Cardiovascular mortality", "glycan_involvement": "Glycosylation affects SGLT2 function and drug response.", "mechanism": "SGLT2 inhibitors lower cardiovascular mortality in HFrEF.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "protective", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "All-cause mortality", "glycan_involvement": "Receptor glycosylation modulates drug efficacy.", "mechanism": "Beta-blockers reduce all-cause mortality in HFrEF.", "protein": "Beta-adrenergic receptor (ADRB1/ADRB2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "All-cause hospitalization", "glycan_involvement": "Glycosylation impacts ACE stability and function.", "mechanism": "ACE inhibitors reduce hospitalization rates in HFrEF.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "protective", "source_pmcid": "PMC12287851" }, { "confidence": "medium", "disease": "Heart failure hospitalization", "glycan_involvement": "Glycosylation may influence receptor activity.", "mechanism": "MRAs may reduce HF hospitalization, though association not statistically significant in this study.", "protein": "Mineralocorticoid receptor (NR3C2)", "relationship_type": "protective", "source_pmcid": "PMC12287851" }, { "confidence": "high", "disease": "Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC)", "glycan_involvement": "Enhances glycan metabolism pathways, affecting tumor progression.", "mechanism": "Promotes proliferation, invasion, metastasis via ECM remodeling, EMT, angiogenesis, and metabolic reprogramming.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "high", "disease": "Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC)", "glycan_involvement": "Associated with increased glycan synthesis/degradation.", "mechanism": "High expression correlates with poor prognosis and advanced histological grade.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "biomarker", "source_pmcid": "PMC12289032" }, { "confidence": "high", "disease": "Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC)", "glycan_involvement": "N-glycosylation critical for integrin function and cell-ECM interaction.", "mechanism": "Regulates cell adhesion, migration, and EMT; collaborates with SERPINH1.", "protein": "ITGA5", "protein_enriched": { "function": "Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct ", "gene_name": "ITGA5", "glycan_count": 121, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G00912UN", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G45395BF", "G46503DX", "G46691LC", "G55220VL", "G57776ZS", "G80075MS", "G81315DD", "G84452RH", "G90659AW", "G11629QQ", "G48905WL", "G55132BD", "G22768VO", "G09724ZC", "G64481DJ", "G83473RC", "G06356OH", "G15169WU", "G22310AV", "G31916IQ", "G47518TP", "G48414YA", "G52527GH", "G55412XP", "G10404TD", "G62765YT", "G80920RR", "G93718GY", "G02815KT", "G05049YU", "G28541PG", "G31852PQ", "G41247ZX", "G62461SM", "G72747WU", "G41891LD", "G13694XX", "G14796IU", "G33791AF", "G47748JZ", "G56784JY", "G81263BG", "G81637OR", "G89865VY", "G22573RC", "G12604EW", "G14994KB", "G18647XP", "G25703UN", "G34617SM", "G40834TG", "G41071NU", "G43223CG", "G45495MK", "G57818FI", "G59324HL", "G60033FS", "G61627IG", "G70441OD", "G70619PT", "G75568BH", "G75983OB", "G79666IR", "G87123QX", "G90382BL", "G92135MA", "G57321FI", "G06110VR", "G11041DA", "G11870QZ", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G23863VK", "G25520XG", "G29880MM", "G36191CD", "G39188ZX", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48954CA", "G50045TK", "G50489VC", "G53752TA", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G72797UR", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G90093AU", "G91365ZQ", "G91413ZX", "G91636VS", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P08648" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "high", "disease": "Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC)", "glycan_involvement": "Modifies collagen, impacting glycoprotein structure in ECM.", "mechanism": "Facilitates collagen maturation, ECM remodeling, and metastasis; acts with SERPINH1.", "protein": "PLOD1", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (", "gene_name": "PLOD1", "glycan_count": 56, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G49108TO", "G02815KT", "G05724UK", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G46902YN", "G60145BJ", "G62765YT", "G63381RX", "G69521XL", "G70101JE", "G83460ZZ", "G00912UN", "G01650EU", "G02886BB", "G06356OH", "G07810QS", "G08290VR", "G08918WF", "G10486CT", "G15664MX", "G23294PN", "G23719VF", "G25451PN", "G27058EU", "G28541PG", "G30221QT", "G41071NU", "G46503DX", "G46524LG", "G48414YA", "G54010QB", "G59626AS", "G59924QI", "G64527OM", "G65092SV", "G65184UU", "G66766XF", "G72747WU", "G72790NZ", "G73968GN", "G75983OB", "G80223IX", "G83229XP", "G84452RH", "G90659AW", "G92050GC", "G93683YO", "G14260UH", "G28681TP", "G45504EY", "G56846UZ", "G57321FI" ], "uniprot_id": "Q02809" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "high", "disease": "Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC)", "glycan_involvement": "Secreted glycoprotein involved in endothelial function.", "mechanism": "Promotes angiogenesis and tumor progression; part of SERPINH1 network.", "protein": "ESM1", "protein_enriched": { "function": "Involved in angiogenesis; promotes angiogenic sprouting. May have potent implications in lung endothelial cell-leukocyte interactions", "gene_name": "ESM1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NQ30" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Regulates ECM glycoprotein folding.", "mechanism": "Promotes collagen deposition and TME remodeling, enhancing invasion and metastasis.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Involved in collagen glycoprotein maturation.", "mechanism": "Enhances tumor cell invasion and metastasis via ECM remodeling.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "Impacts ECM glycoprotein structure.", "mechanism": "Induces chemoresistance through AKT signaling activation.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "causal", "source_pmcid": "PMC12289032" }, { "confidence": "medium", "disease": "Kidney renal papillary cell carcinoma (KIRP)", "glycan_involvement": "ECM glycoprotein regulation.", "mechanism": "High expression predicts poor prognosis; part of SERPINH1-PLOD1-ITGA5-ESM1 network.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "biomarker", "source_pmcid": "PMC12289032" }, { "confidence": "medium", "disease": "Brain lower grade glioma (LGG)", "glycan_involvement": "ECM glycoprotein regulation.", "mechanism": "High expression predicts poor prognosis; part of SERPINH1-PLOD1-ITGA5-ESM1 network.", "protein": "SERPINH1", "protein_enriched": { "function": "Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen", "gene_name": "SERPINH1", "glycan_count": 52, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G08918WF", "G10256JP", "G11314AS", "G11870QZ", "G14669DU", "G14994KB", "G15664MX", "G18647XP", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G33609NS", "G35029YA", "G36379GD", "G39188ZX", "G39446WN", "G41247ZX", "G46503DX", "G46687AB", "G49874UX", "G50757KG", "G57317CE", "G59626AS", "G60145BJ", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G74724QE", "G80920RR", "G83460ZZ", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G13144LI", "G72735IY", "G74430RZ", "G80333GO", "G82119TF", "G49108TO" ], "uniprot_id": "P50454" }, "relationship_type": "biomarker", "source_pmcid": "PMC12289032" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Direct binding to fucosylated blood group A, B, and H antigens on type 1 glycan chains is essential for host cell entry.", "mechanism": "VP8* mediates viral attachment to host cells by binding blood group ABH antigens on type 1 chains, facilitating infection.", "protein": "VP8* (P[28])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Recognition of fucosylated ABH antigens and mucin O-glycans enables infection.", "mechanism": "VP8* binds blood group ABH antigens on type 1 chains and mucin O-glycan cores 2 and 4, mediating host cell attachment.", "protein": "VP8* (P[10])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Binding to fucosylated H and Lewis b antigens on type 1 chains.", "mechanism": "VP8* binds H type 1 and Lewis antigens on host cells, promoting viral entry.", "protein": "VP8* (P[8])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Recognition of fucosylated glycans on type 1 chains.", "mechanism": "VP8* binds H type 1, A antigen, and Lewis b antigens, mediating infection.", "protein": "VP8* (P[4])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Binding to fucosylated and mucin-type O-glycans.", "mechanism": "VP8* binds H type 1, A antigen, internal Lewis x, and mucin O-glycan core 2, facilitating infection.", "protein": "VP8* (P[6])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Recognition of fucosylated and O-glycosylated structures.", "mechanism": "VP8* binds H type 1 and mucin O-glycan cores, mediating host cell attachment.", "protein": "VP8* (P[19])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "medium", "disease": "Severe diarrhea in young children", "glycan_involvement": "Host susceptibility determined by presence of specific fucosylated glycans.", "mechanism": "VP8* enables rotavirus infection by binding blood group ABH antigens on type 1 chains in children.", "protein": "VP8* (P[28])", "relationship_type": "causal", "source_pmcid": "PMC12289080" }, { "confidence": "medium", "disease": "Acute gastroenteritis (rotavirus infection)", "glycan_involvement": "Ability to bind multiple blood group antigens on type 1 chains may facilitate cross-species transmission.", "mechanism": "P[28] strain may represent a reassortment between bat and human RVs, with broad glycan binding specificity raising epidemic risk.", "protein": "VP8* (P[28])", "relationship_type": "potential causal (zoonotic risk)", "source_pmcid": "PMC12289080" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation is essential for receptor folding, stability, and activation; aberrant glycosylation leads to ligand-independent activation and drug resistance.", "mechanism": "EGFR mutations and aberrant glycosylation drive oncogenic signaling and tumor growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "high", "disease": "Therapeutic resistance in lung cancer", "glycan_involvement": "Inhibition of N-glycosylation (e.g., with OST inhibitors) restores sensitivity to EGFR TKIs.", "mechanism": "Altered glycosylation contributes to resistance to EGFR inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12289112" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation at specific sites interferes with antibody binding and receptor stability.", "mechanism": "HER-2 overexpression/amplification and glycosylation promote tumor proliferation.", "protein": "HER-2", "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "high", "disease": "Therapeutic resistance in lung cancer", "glycan_involvement": "ST6Gal1-mediated sialylation of N-glycans impairs trastuzumab binding; inhibition of ST6Gal1 increases drug sensitivity.", "mechanism": "N-glycosylation in the trastuzumab-binding domain reduces antibody efficacy.", "protein": "HER-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12289112" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycans in the SEMA domain enhance HGF signaling; O-glycosylation (C1GALT1, GALNT2) modulates dimerization and activation.", "mechanism": "c-MET mutations/amplifications and glycosylation regulate oncogenic signaling.", "protein": "c-MET", "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "medium", "disease": "Therapeutic resistance in lung cancer", "glycan_involvement": "Targeting glycosylation may enhance efficacy of c-MET inhibitors and overcome resistance.", "mechanism": "c-MET amplification mediates resistance to EGFR TKIs.", "protein": "c-MET", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12289112" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation is essential for ALK phosphorylation and downstream signaling.", "mechanism": "ALK fusions drive oncogenesis; glycosylation is required for receptor activation.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "medium", "disease": "Therapeutic resistance in lung cancer", "glycan_involvement": "Inhibition of N-glycosylation impairs ALK signaling and may sensitize to inhibitors.", "mechanism": "Glycosylation affects ALK-driven resistance mechanisms.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12289112" }, { "confidence": "low", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Three O-glycosylation sites (Ser1570, Ser1577, Ser1581) may impact receptor function.", "mechanism": "ROS1 fusions drive oncogenesis; glycosylation sites suggest functional relevance.", "protein": "ROS1", "protein_enriched": { "function": "Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous s", "gene_name": "ROS1", "glycan_count": 1, "glycosylation_sites_count": 30, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08922" }, "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "low", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Four N-glycosylation sites (Asn343, Asn554, Asn763, Asn975) reported.", "mechanism": "RET rearrangements drive oncogenesis; glycosylation sites identified but functional impact unclear.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "causal", "source_pmcid": "PMC12289112" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury", "glycan_involvement": "Altered glycosylation may affect cell surface stability and stress response.", "mechanism": "Steatotic hepatocytes are more susceptible to ischemia-reperfusion injury, leading to cell death and graft dysfunction.", "protein": "Hepatocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "medium", "disease": "Fat embolism syndrome", "glycan_involvement": "Glycoprotein coating may affect fat droplet stability and immune recognition.", "mechanism": "Rupture of fat-laden hepatocytes releases fat globules, some associated with glycoproteins, causing emboli.", "protein": "Fat droplet-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "low", "disease": "Lipopeliosis", "glycan_involvement": "Endothelial glycoproteins mediate barrier function; altered glycosylation may increase susceptibility.", "mechanism": "Fat globules disrupt sinusoidal endothelium, leading to lipopeliosis.", "protein": "Sinusoidal endothelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Cytokine glycosylation affects secretion and activity.", "mechanism": "Fat emboli trigger cytokine release, causing inflammatory lung injury.", "protein": "Cytokines (e.g., IL-6, TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "low", "disease": "Cholestasis", "glycan_involvement": "Glycosylation is critical for bile duct function.", "mechanism": "Injury to bile duct glycoproteins impairs bile flow, leading to cholestasis.", "protein": "Bile duct epithelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "medium", "disease": "Hyperfibrinolysis", "glycan_involvement": "Glycosylation affects fibrinogen stability and function.", "mechanism": "Liver dysfunction impairs fibrinogen synthesis, contributing to bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12290766" }, { "confidence": "low", "disease": "Persistent ascites", "glycan_involvement": "Glycosylation modulates albumin half-life.", "mechanism": "Reduced albumin synthesis due to graft dysfunction leads to ascites.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12290766" }, { "confidence": "low", "disease": "Primary non-function", "glycan_involvement": "Glycosylation pattern changes reflect liver injury.", "mechanism": "Altered transferrin glycoforms indicate liver synthetic failure.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12290766" }, { "confidence": "low", "disease": "Multi-organ failure", "glycan_involvement": "Glycosylation modulates immune effector function.", "mechanism": "Immune activation and altered immunoglobulin glycosylation may contribute to systemic inflammation.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12290766" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation is essential for BSEP trafficking and function.", "mechanism": "Injury or dysfunction of BSEP impairs bile salt export, causing cholestasis.", "protein": "Bile salt export pump (BSEP)", "protein_enriched": { "function": "Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore par", "gene_name": "ABCB11", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "O95342" }, "relationship_type": "causal", "source_pmcid": "PMC12290766" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Specific glycan epitopes (e.g., \u03b1(1\u21926)-galactose, \u03b1(1\u21923)-rhamnose) are recognized by host antibodies.", "mechanism": "LPS is a major virulence factor triggering host immune response and inflammation in periodontitis.", "protein": "LPS of Porphyromonas gingivalis", "relationship_type": "causal", "source_pmcid": "PMC12291450" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "LPS glycan motifs are immunogenic and drive systemic immune responses.", "mechanism": "Translocation of P. gingivalis LPS to remote tissues promotes systemic inflammation and arteriosclerotic lesions.", "protein": "LPS of Porphyromonas gingivalis", "relationship_type": "causal", "source_pmcid": "PMC12291450" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "LPS glycan structures may contribute to immune activation.", "mechanism": "Association via systemic inflammation and possible neuroinflammatory effects of LPS.", "protein": "LPS of Porphyromonas gingivalis", "relationship_type": "causal", "source_pmcid": "PMC12291450" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycan epitopes on LPS are recognized by host antibodies, possibly contributing to autoimmunity.", "mechanism": "LPS triggers immune responses linked to systemic autoimmunity.", "protein": "LPS of Porphyromonas gingivalis", "relationship_type": "causal", "source_pmcid": "PMC12291450" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Terminal \u03b1(1\u21926)-galactose is key for antibody recognition.", "mechanism": "High IgG antibody levels against this epitope in saliva/serum of periodontitis patients.", "protein": "LPS-tetrasaccharide (\u03b1-d-Galp-(1\u21926)-\u03b1-d-Glcp-(1\u21924)-\u03b1-l-Rhap-(1\u21923)-\u03b2-d-GalNAc)", "relationship_type": "biomarker", "source_pmcid": "PMC12291450" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Terminal \u03b1(1\u21923)-rhamnose motif is immunodominant.", "mechanism": "Elevated IgG antibody levels in periodontitis patients compared to healthy controls.", "protein": "LPS-trisaccharide (terminal \u03b1(1\u21923)-rhamnose)", "relationship_type": "biomarker", "source_pmcid": "PMC12291450" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation pattern is essential for immunogenicity and vaccine efficacy.", "mechanism": "Synthetic glycoconjugate vaccine using this epitope elicits protective IgG responses in mice.", "protein": "LPS-tetrasaccharide (\u03b1-d-Galp-(1\u21926)-\u03b1-d-Glcp-(1\u21924)-\u03b1-l-Rhap-(1\u21923)-\u03b2-d-GalNAc)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12291450" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Conjugated glycan epitope is required for immune protection.", "mechanism": "Immunization induces IgG antibodies that bind both synthetic glycan and P. gingivalis W50 bacteria.", "protein": "CRM197-LPS-2 glycoconjugate", "relationship_type": "protective", "source_pmcid": "PMC12291450" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Terminal \u03b1(1\u21923)-rhamnose glycan is immunogenic but less effective for bacterial targeting.", "mechanism": "Immunization induces IgG antibodies against synthetic glycan, but not effective in bacterial binding ELISA.", "protein": "CRM197-LPS-5 glycoconjugate", "relationship_type": "protective", "source_pmcid": "PMC12291450" }, { "confidence": "medium", "disease": "Systemic diseases (atherosclerosis, Alzheimer\u2019s, rheumatoid arthritis)", "glycan_involvement": "Glycan motifs are central to immunogenicity and vaccine design.", "mechanism": "Vaccines targeting LPS glycan epitopes may prevent systemic diseases linked to periodontitis.", "protein": "LPS of Porphyromonas gingivalis", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12291450" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau aggregation is seeded by glycosaminoglycan heparin; glycosylation not directly discussed.", "mechanism": "Hyperphosphorylation and aggregation of tau leads to neurofibrillary tangles and neuronal dysfunction.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "high", "disease": "Frontotemporal lobar degeneration with tau pathology", "glycan_involvement": "Heparin (glycosaminoglycan) can seed tau aggregation in vitro.", "mechanism": "Pathological accumulation and aggregation of tau protein drives neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "medium", "disease": "Chronic traumatic encephalopathy", "glycan_involvement": "Heparin can seed tau aggregation; glycosylation not directly discussed.", "mechanism": "Tau hyperphosphorylation and aggregation following trauma and iron dyshomeostasis.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "medium", "disease": "Pick\u2019s disease", "glycan_involvement": "Heparin can seed tau aggregation; glycosylation not directly discussed.", "mechanism": "Tau aggregation and NFT formation are central to pathology.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "medium", "disease": "Corticobasal degeneration", "glycan_involvement": "Heparin can seed tau aggregation; glycosylation not directly discussed.", "mechanism": "Tau aggregation and hyperphosphorylation drive neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "medium", "disease": "Progressive supranuclear palsy", "glycan_involvement": "Heparin can seed tau aggregation; glycosylation not directly discussed.", "mechanism": "Tau aggregation and hyperphosphorylation drive neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12292136" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "APO is a glycoprotein; glycosylation required for function but not directly linked to tauopathy mechanism here.", "mechanism": "APO is an iron-chelating glycoprotein reported to be protective against iron-mediated neurodegeneration, but ineffective against hemin-induced tau pathology in this study.", "protein": "Apotransferrin (APO)", "relationship_type": "protective", "source_pmcid": "PMC12292136" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau aggregation seeded by heparin (glycosaminoglycan); glycosylation not directly discussed.", "mechanism": "Tau aggregation can be inhibited by uric acid and DOT, suggesting therapeutic potential.", "protein": "Tau protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12292136" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycosylation involvement in biomarker use.", "mechanism": "Phosphorylated tau (AT8 epitope) is used as a biomarker for tau pathology progression.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC12292136" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heparin is a glycosaminoglycan; its glycan structure is essential for tau aggregation seeding.", "mechanism": "Heparin acts as a cofactor to seed tau aggregation in vitro, modeling disease mechanism.", "protein": "Heparin", "relationship_type": "causal (in vitro)", "source_pmcid": "PMC12292136" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia", "glycan_involvement": "Glycosylation is essential for P-glycoprotein stability and drug efflux function.", "mechanism": "High ABCB1 expression correlates with poor survival in AML patients treated with anthracyclines.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for proper membrane localization and activity.", "mechanism": "High ABCB1 expression predicts worse survival in myeloma patients receiving anthracyclines.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "N-glycosylation modulates efflux capacity and drug resistance.", "mechanism": "Elevated ABCB1 expression is associated with reduced survival in HCC patients on anthracycline therapy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation stabilizes transporter and supports drug efflux.", "mechanism": "Overexpression in NCI-ADR-Res cells causes acquired resistance to anthracyclines.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Multidrug Resistance in Cancer", "glycan_involvement": "Glycosylation required for functional drug efflux.", "mechanism": "Efflux of anthracyclines and other drugs leads to MDR phenotype.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12292137" }, { "confidence": "medium", "disease": "Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3)", "glycan_involvement": "Glycosylation affects membrane trafficking and function.", "mechanism": "ABCB4 transports phosphatidylcholine; mutations cause PFIC3.", "protein": "ABCB4", "protein_enriched": { "function": "Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the", "gene_name": "ABCB4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21439" }, "relationship_type": "causal", "source_pmcid": "PMC12292137" }, { "confidence": "medium", "disease": "Multidrug Resistance in Cancer", "glycan_involvement": "N-glycosylation influences substrate specificity and stability.", "mechanism": "Contributes to MDR by efflux of drugs, though not major for anthracyclines in inherent resistance.", "protein": "ABCC1/MRP1", "relationship_type": "causal", "source_pmcid": "PMC12292137" }, { "confidence": "medium", "disease": "Multidrug Resistance in Cancer", "glycan_involvement": "N-glycosylation required for surface expression and function.", "mechanism": "Effluxes various drugs; not a major factor for anthracycline resistance in inherent settings.", "protein": "ABCG2/BCRP", "relationship_type": "causal", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Anthracycline Resistance", "glycan_involvement": "Glycosylation sites may be targeted to modulate activity.", "mechanism": "Targeting ABCB1 may overcome resistance to anthracyclines in cancer.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12292137" }, { "confidence": "medium", "disease": "Collateral Sensitivity in MDR Cancer", "glycan_involvement": "Glycosylation maintains transporter function; altered substrate specificity may bypass efflux.", "mechanism": "Certain anthracycline derivatives (e.g., compound 1) induce hypersensitivity in MDR cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "protective", "source_pmcid": "PMC12292137" }, { "confidence": "high", "disease": "Decompensated Congestive Heart Failure", "glycan_involvement": "CA-125 is a heavily O-glycosylated mucin; glycosylation is essential for its secretion and detection.", "mechanism": "CA-125 is elevated in response to systemic congestion and serosal activation in HF.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "high", "disease": "Systemic Congestion", "glycan_involvement": "Glycosylation enables CA-125's role as a marker of serosal activation.", "mechanism": "CA-125 levels correlate with the degree of systemic congestion, reflecting serosal inflammation.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Aberrant glycosylation in cancer increases CA-125 shedding.", "mechanism": "CA-125 is used clinically to monitor ovarian cancer due to its overexpression in malignant serous tissues.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "medium", "disease": "Right Ventricular Failure", "glycan_involvement": "Glycosylation is required for CA-125's stability and detection.", "mechanism": "Elevated CA-125 is associated with hepatic congestion and RV dysfunction.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "high", "disease": "Decompensated Congestive Heart Failure", "glycan_involvement": "Glycosylation affects CA-125's circulating levels and immunoreactivity.", "mechanism": "High CA-125 predicts increased mortality; low CA-125 identifies patients with better prognosis.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation is necessary for CA-125's secretion.", "mechanism": "AF and its recurrence are linked to elevated CA-125, possibly via increased serosal inflammation.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "high", "disease": "Decompensated Congestive Heart Failure", "glycan_involvement": "NT-proBNP is glycosylated, which affects its stability and clearance.", "mechanism": "NT-proBNP is a validated marker for cardiac dysfunction and congestion.", "protein": "N-terminal pro-brain natriuretic peptide (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "medium", "disease": "Cardiorenal Syndrome", "glycan_involvement": "Glycosylation ensures CA-125's renal-independent clearance.", "mechanism": "CA-125 is not affected by renal function, distinguishing it from other markers in cardiorenal syndrome.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "medium", "disease": "Systemic Congestion", "glycan_involvement": "Glycosylation status may influence CA-125's release and detection.", "mechanism": "Low CA-125 in systemic congestion is associated with preserved cardiac function and improved survival.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "protective", "source_pmcid": "PMC12292425" }, { "confidence": "medium", "disease": "Decompensated Congestive Heart Failure", "glycan_involvement": "Glycosylation is critical for CA-125's immunogenicity and cross-reactivity.", "mechanism": "CA-125 is not heart-specific and may be elevated in other inflammatory or oncological conditions.", "protein": "Carbohydrate Antigen 125 (CA-125)", "relationship_type": "experimental biomarker", "source_pmcid": "PMC12292425" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "Binds \u03b2-galactoside glycans on T cells, integrins, and ECM proteins; glycosylation density modulates activity.", "mechanism": "Promotes immune evasion, stromal activation, angiogenesis, EMT, and therapy resistance via glycan-mediated signaling and integrin clustering.", "protein": "Galectin-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Intestinal Metaplasia", "glycan_involvement": "Increased \u03b2-galactoside structures in IM enhance Gal-1 binding.", "mechanism": "Upregulated in IM lesions, especially in epithelium and stroma; may drive epithelial transformation and stromal remodeling.", "protein": "Galectin-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Peritoneal Carcinomatosis", "glycan_involvement": "Interacts with ECM glycoproteins; glycan lattices facilitate cell adhesion and invasion.", "mechanism": "Promotes peritoneal fibrosis and metastatic niche formation by increasing collagen and fibronectin deposition.", "protein": "Galectin-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "Glycan-mediated receptor clustering affects drug uptake and signaling.", "mechanism": "Activates MAPK and PI3K/AKT pathways, enhances stemness, and reduces cisplatin sensitivity.", "protein": "Galectin-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "Binds poly-N-acetyllactosamine glycans on integrins and ECM; glycosylation modulates adhesion and migration.", "mechanism": "Promotes proliferation, invasion, apoptosis resistance, and immune evasion via \u03b2-catenin/TCF-4, AKT, and ECM remodeling.", "protein": "Galectin-3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Peritoneal Carcinomatosis", "glycan_involvement": "Exosomal Gal-3 binds glycosylated integrins and ECM proteins, driving niche formation.", "mechanism": "Exosomal Gal-3 remodels peritoneal stroma, activates CAFs, and induces CXCL12-rich niche for metastasis.", "protein": "Galectin-3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "Glycan-dependent nuclear translocation and transcriptional regulation.", "mechanism": "Upregulates antiapoptotic proteins (survivin, XIAP), cyclin D1, and hTERT, conferring resistance to chemotherapy.", "protein": "Galectin-3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Epithelial\u2013Mesenchymal Transition", "glycan_involvement": "Glycan binding modulates cell\u2013cell and cell\u2013matrix adhesion.", "mechanism": "Induces EMT via Wnt/\u03b2-catenin/TCF-4 and cytoskeletal remodeling (Fascin-1, HMMR).", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12293135" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Binds \u03b2-galactoside glycans on TIM-3 and immune cells.", "mechanism": "High Gal-9 expression correlates with longer survival; modulates T-cell exhaustion and immune regulation.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "N-glycosylation of integrin modulates Galectin binding and signaling.", "mechanism": "Cooperates with Gal-1 and Gal-3 to drive invasion, EMT, and metastatic progression.", "protein": "\u03b21 Integrin", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12293135" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates adhesive properties and ECM interactions.", "mechanism": "Upregulated in DMD muscle, mediates cell-to-cell and cell-to-matrix interactions, contributing to ECM remodeling and fibrosis.", "protein": "Thrombospondin-4 (THBS4)", "protein_enriched": { "function": "NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction", "gene_name": "CYB5R1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UHQ9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Hydroxylation and glycosylation of collagen are essential for fibril formation and stability.", "mechanism": "Strongly upregulated in DMD, drives excessive ECM deposition and muscle fibrosis.", "protein": "Collagen type I alpha 1 (COL1A1)", "relationship_type": "causal", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects collagen triple helix formation and ECM integrity.", "mechanism": "Upregulated in DMD, contributes to fibrotic ECM accumulation and impaired muscle regeneration.", "protein": "Collagen type I alpha 2 (COL1A2)", "relationship_type": "causal", "source_pmcid": "PMC12294368" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation may influence FACIT collagen interactions with fibrillar collagens.", "mechanism": "Upregulated in DMD, associated with altered ECM structure and fibrosis.", "protein": "Collagen type XIX alpha 1 (COL19A1)", "protein_enriched": { "function": "", "gene_name": "GLT8D2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H1C3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects membrane association and ECM binding.", "mechanism": "Upregulated in DMD, may contribute to ECM changes and muscle pathology.", "protein": "Collagen type XXV alpha 1 (COL25A1)", "protein_enriched": { "function": "Plays a role during the calcification of cartilage and the transition of cartilage to bone", "gene_name": "COL27A1", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G53434XO" ], "uniprot_id": "Q8IZC6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation regulates secretion and activity of MMP9.", "mechanism": "Upregulated in DMD, promotes ECM degradation and fibrosis progression.", "protein": "Matrix metalloproteinase-9 (MMP9)", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (By", "gene_name": "Mmp9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P50282" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates TIMP1 stability and inhibitory function.", "mechanism": "Upregulated in DMD, inhibits MMPs, contributing to ECM accumulation and fibrosis.", "protein": "Tissue inhibitor of metalloproteinases 1 (TIMP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects cell adhesion and ECM assembly.", "mechanism": "Upregulated in DMD, involved in ECM organization and fibrosis.", "protein": "Fibronectin (FN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation modulates immune cell interactions.", "mechanism": "Upregulated in DMD, promotes inflammation and fibrosis.", "protein": "Osteopontin (SPP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation influences CTGF secretion and ECM binding.", "mechanism": "Upregulated in DMD, amplifies TGF-\u03b2-induced fibrosis and inhibits myogenesis.", "protein": "Connective tissue growth factor (CTGF)", "protein_enriched": { "function": "Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes. Is involved in the stimulation of osteoblast differentiation ", "gene_name": "CCN2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P29279" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12294368" }, { "confidence": "high", "disease": "DMD-associated Cardiomyopathy", "glycan_involvement": "Chondroitin sulfate glycosaminoglycan chains mediate ECM interactions and inhibit innervation.", "mechanism": "CSPG4 is overexpressed in dystrophic hearts, drives pathological ECM remodeling and fibrosis; targeting CSPG4 with CAR-T cells reduces fibrosis and improves cardiac function.", "protein": "CSPG4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12294788" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Altered sulfation/glycosylation patterns enhance fibrotic signaling.", "mechanism": "CSPG4 accumulation promotes fibroblast activation and excessive ECM deposition.", "protein": "CSPG4", "relationship_type": "causal", "source_pmcid": "PMC12294788" }, { "confidence": "medium", "disease": "DMD-associated Cardiomyopathy", "glycan_involvement": "Heavily glycosylated; glycan chains required for ECM binding and muscle integrity.", "mechanism": "Upregulation of Dag1 (dystroglycan 1) after CSPG4.CAR-T therapy may stabilize the dystrophin\u2013glycoprotein complex, compensating for dystrophin loss.", "protein": "Dag1", "relationship_type": "protective", "source_pmcid": "PMC12294788" }, { "confidence": "medium", "disease": "DMD-associated Cardiomyopathy", "glycan_involvement": "Glycosylation required for complex assembly.", "mechanism": "Restoration of Sgcb expression after therapy supports sarcoglycan complex stability and muscle membrane integrity.", "protein": "Sgcb", "relationship_type": "protective", "source_pmcid": "PMC12294788" }, { "confidence": "medium", "disease": "DMD-associated Cardiomyopathy", "glycan_involvement": "Glycosylation important for function.", "mechanism": "Sgcd upregulation post-treatment may help stabilize muscle cell membranes.", "protein": "Sgcd", "relationship_type": "protective", "source_pmcid": "PMC12294788" }, { "confidence": "medium", "disease": "DMD-associated Cardiomyopathy", "glycan_involvement": "Glycosylation required for sarcoglycan complex function.", "mechanism": "Sgcg restoration after CSPG4.CAR-T therapy may support membrane stability.", "protein": "Sgcg", "relationship_type": "protective", "source_pmcid": "PMC12294788" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "N- and O-glycosylation modulate ECM interactions.", "mechanism": "Fibronectin gene expression is elevated in dystrophic hearts and reduced after CSPG4-targeted therapy.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12294788" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Hydroxylysine glycosylation affects fibril formation.", "mechanism": "Col1a1 upregulated in DMD cardiomyopathy; reduced after CSPG4.CAR-T therapy.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "biomarker", "source_pmcid": "PMC12294788" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates ECM structure.", "mechanism": "Col3a1 elevated in dystrophic hearts; normalized after CSPG4-targeted therapy.", "protein": "Collagen type III", "relationship_type": "biomarker", "source_pmcid": "PMC12294788" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Chondroitin sulfate chains alter ECM mechanical properties.", "mechanism": "CSPG4-driven ECM remodeling increases myocardial stiffness, predisposing to arrhythmias.", "protein": "CSPG4", "relationship_type": "causal", "source_pmcid": "PMC12294788" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is part of the dystrophin-glycoprotein complex, which relies on glycosylation for membrane stability.", "mechanism": "Loss-of-function mutations in DMD gene lead to absence of functional dystrophin, causing progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12295302" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation of dystrophin-glycoprotein complex contributes to residual membrane stability.", "mechanism": "In-frame mutations allow production of truncated, partially functional dystrophin, resulting in milder phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12295302" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of associated glycoproteins in the complex is critical for cardiac muscle integrity.", "mechanism": "Absence of dystrophin in cardiac muscle leads to membrane instability and cardiac degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12295302" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "TfR1 is a glycoprotein; glycosylation affects antibody binding and tissue targeting.", "mechanism": "AOC1044 therapy uses anti-TfR1 antibody to deliver PMOs to muscle cells, enhancing dystrophin restoration.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12295302" }, { "confidence": "medium", "disease": "Renal toxicity", "glycan_involvement": "Glycosylation affects stability and filtration of \u03b22 microglobulin.", "mechanism": "Elevated urinary \u03b22 microglobulin indicates renal tubular stress during PMO therapy.", "protein": "\u03b22 microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12295302" }, { "confidence": "medium", "disease": "Renal toxicity", "glycan_involvement": "Albumin glycosylation influences renal filtration and biomarker reliability.", "mechanism": "Increased albumin/creatinine ratio in urine signals kidney stress in PMO-treated patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12295302" }, { "confidence": "medium", "disease": "Renal toxicity", "glycan_involvement": "Glycosylation modulates cystatin C stability and excretion.", "mechanism": "Elevated urinary cystatin C is a marker of renal function during PMO therapy.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12295302" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Glycosylation may affect immunogenicity of off-target proteins.", "mechanism": "Potential off-target binding by NS-089/NCNP-02 may produce non-native protein, causing inflammation and fever.", "protein": "Phosphodiesterase 3B", "protein_enriched": { "function": "Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or ", "gene_name": "PDE8A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60658" }, "relationship_type": "off-target/causal", "source_pmcid": "PMC12295302" }, { "confidence": "low", "disease": "Blood pressure dysregulation", "glycan_involvement": "Glycosylation may influence channel function and immunogenicity.", "mechanism": "Potential off-target binding by NS-089/NCNP-02 could affect blood pressure regulation.", "protein": "Transient receptor potential cation channel subfamily M member 3 (TRPM3)", "protein_enriched": { "function": "Constitutively active, non-selective divalent cation-conducting channel that is permeable to Ca(2+), Mn(2+), and Mg(2+), with a high permeability for Ca(2+). However, can be enhanced by increasing tem", "gene_name": "TRPM3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9HCF6" }, "relationship_type": "off-target/causal", "source_pmcid": "PMC12295302" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation of complex members is essential for structural integrity and signaling.", "mechanism": "Disruption of the glycoprotein complex due to lack of dystrophin leads to membrane instability and muscle degeneration.", "protein": "Sarcolemma dystrophin-glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12295302" }, { "confidence": "high", "disease": "Leukocyte Adhesion Deficiency II (LADII)", "glycan_involvement": "Impaired fucosylation of selectin ligands on leukocytes.", "mechanism": "Defective GDP-fucose transport to Golgi impairs selectin-mediated neutrophil rolling.", "protein": "SLC35C1", "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Defective N-glycan core fucosylation on neural proteins.", "mechanism": "Loss of core fucosylation affects neuronal development and function.", "protein": "FUT8", "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "Altered GDP-fucose synthesis affects glycoprotein stress response in eye.", "mechanism": "SNPs in GMDS associated with increased glaucoma risk and optic nerve damage.", "protein": "GMDS", "relationship_type": "risk factor", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Stroke / Cerebral Small Vessel Disease (CSVD)", "glycan_involvement": "Reduced fucosylation impacts vascular integrity.", "mechanism": "GMDS variants linked to increased white matter hyperintensity and stroke risk.", "protein": "GMDS", "relationship_type": "risk factor", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Cancer (colorectal, lung, breast, HCC)", "glycan_involvement": "N-glycan core fucosylation changes on growth factor receptors.", "mechanism": "Altered core fucosylation promotes tumor progression and metastasis.", "protein": "FUT8", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Cancer (HCC, germ cell tumors)", "glycan_involvement": "Elevated fucosylated glycoforms detected in cancer patients.", "mechanism": "Increased fucosylation of alpha-fetoprotein in serum marks early tumor formation.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Dowling-Degos Disease (DDD)", "glycan_involvement": "Defective O-fucosylation on EGF repeats of skin proteins.", "mechanism": "Missense mutation impairs O-fucosylation of EGF repeats, affecting melanin transport.", "protein": "POFUT1", "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Bombay Blood Group", "glycan_involvement": "Absence of fucosylated H antigen on RBCs.", "mechanism": "Loss of \u03b11,2-fucosyltransferase activity prevents H antigen synthesis.", "protein": "FUT1", "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "CADASIL", "glycan_involvement": "Defective O-fucosylation on Notch3 EGF repeats.", "mechanism": "Mutations in EGF repeats impair fucosylation and Fringe extension, disrupting Notch signaling.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Congenital Scoliosis/Spondylocostal Dysostosis", "glycan_involvement": "Abnormal O-fucose glycan elongation on Notch pathway proteins.", "mechanism": "Mutations impair extension of O-fucose on Notch EGF repeats, affecting vertebral development.", "protein": "Fringe proteins", "relationship_type": "causal", "source_pmcid": "PMC12295658" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin organizes DAPC, which includes glycoproteins; loss disrupts glycoprotein complex.", "mechanism": "Loss-of-function mutations in dystrophin gene cause absence of dystrophin, leading to DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Alpha-dystroglycan requires extensive O-glycosylation for ECM binding; disruption impairs function.", "mechanism": "Loss of dystrophin disrupts DAPC, affecting alpha-dystroglycan's ECM binding and muscle integrity.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Beta-dystroglycan is glycosylated; loss of DAPC affects its membrane stability.", "mechanism": "DAPC disassembly impairs beta-dystroglycan's role in linking cytoskeleton to ECM.", "protein": "Beta-dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Sarcoglycans are glycoproteins; glycosylation is essential for complex stability.", "mechanism": "DAPC disassembly leads to loss of sarcoglycan complex, contributing to membrane fragility.", "protein": "Sarcoglycans", "relationship_type": "causal", "source_pmcid": "PMC12295774" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Defective O-glycosylation reduces ECM interaction, leading to fibrotic replacement.", "mechanism": "Disrupted glycosylation of alpha-dystroglycan impairs muscle regeneration, promoting fibrosis.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "DAPC glycoproteins in heart are affected by dystrophin loss.", "mechanism": "Loss of dystrophin in cardiac muscle leads to membrane instability and cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Not directly glycosylated; reflects glycoprotein complex disruption.", "mechanism": "CK leaks into plasma due to sarcolemmal damage in DMD.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Micro-dystrophin reassembles DAPC, restoring glycoprotein interactions.", "mechanism": "Gene therapy delivers micro-dystrophin to partially restore DAPC and muscle function.", "protein": "Micro-dystrophin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Indirect; HDAC inhibition restores expression of glycoproteins involved in muscle repair.", "mechanism": "HDAC inhibitors (e.g., givinostat) rebalance epigenetic regulation, improving muscle regeneration.", "protein": "Histone deacetylases (HDACs)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation of alpha-dystroglycan remains partially intact.", "mechanism": "Partially functional dystrophin preserves DAPC and alpha-dystroglycan function, resulting in milder disease.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/protective", "source_pmcid": "PMC12295774" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Altered Fc glycosylation modulates immune response.", "mechanism": "IgG Fc glycosylation patterns change during sepsis and are influenced by neutrophil depletion.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "NE is a glycoprotein; glycosylation may affect stability/activity.", "mechanism": "Elevated NE-DNA complexes in serum correlate with disease severity.", "protein": "Neutrophil Elastase (NE)", "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "MPO glycosylation may influence NET formation.", "mechanism": "Elevated MPO-DNA complexes in serum correlate with disease severity.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may affect DNase I activity.", "mechanism": "DNase I activity is insufficient to degrade NETs in moderate/severe psoriasis.", "protein": "DNase I", "protein_enriched": { "function": "Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:11241278, PubMed:2251263, PubMed:2277032). Expressed by non-hematopoietic tissues and preferenti", "gene_name": "DNASE1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G37412TK", "G95977AE" ], "uniprot_id": "P24855" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12295785" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Histone acetylation/citrullination modulates NET formation.", "mechanism": "Citrullinated histones are elevated and correlate with disease severity.", "protein": "Histones (H3, citH3)", "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "NET-associated inflammation", "glycan_involvement": "Histone acetylation (not classical glycosylation) modulates NET formation.", "mechanism": "Sodium acetate enhances histone acetylation, increasing NOX-independent NET formation.", "protein": "Histones (H3, Ace-H3, H3K9, H3K14)", "relationship_type": "causal", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "Bovine Besnoitiosis", "glycan_involvement": "AMPK is a glycoprotein; glycosylation may affect function.", "mechanism": "AMPK activation synergizes with autophagy to promote NET formation in response to B. besnoiti.", "protein": "AMP-activated protein kinase (AMPK)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "Bovine Besnoitiosis", "glycan_involvement": "CAMKK2 glycosylation may modulate activity.", "mechanism": "CAMKK2 activation is upstream of AMPK in NET formation.", "protein": "Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)", "protein_enriched": { "function": "Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAM", "gene_name": "CAMKK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96RR4" }, "relationship_type": "causal", "source_pmcid": "PMC12295785" }, { "confidence": "high", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Histone modifications regulate NET formation.", "mechanism": "NET formation (including citrullinated histones) is elevated in UC and normalizes after remission.", "protein": "Histones (H3, citH3)", "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "IgG glycosylation may modulate inflammation.", "mechanism": "NET formation and neutrophil levels are elevated in IBD, possibly affecting IgG glycosylation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12295785" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation contributes to DEP-1 molecular weight and function.", "mechanism": "DEP-1 regulates insulin signaling; altered glycosylation affects its activity and cellular localization.", "protein": "DEP-1 (Density-enhanced phosphatase-1)", "protein_enriched": { "function": "Plays a role in vesicle-mediated secretory processes (PubMed:24843546). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity). Required", "gene_name": "PTPRN", "glycan_count": 11, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G49108TO", "G02815KT", "G15664MX", "G23719VF", "G36379GD", "G57317CE", "G84349RE", "G92050GC", "G92275SC" ], "uniprot_id": "Q16849" }, "relationship_type": "biomarker", "source_pmcid": "PMC12296425" }, { "confidence": "low", "disease": "Neurodegenerative Disease", "glycan_involvement": "N-glycosylation affects DEP-1 stability and signaling in brain tissue.", "mechanism": "DEP-1 is expressed in neuronal cells; glycosylation may influence neuronal signaling and disease progression.", "protein": "DEP-1 (Density-enhanced phosphatase-1)", "protein_enriched": { "function": "Plays a role in vesicle-mediated secretory processes (PubMed:24843546). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity). Required", "gene_name": "PTPRN", "glycan_count": 11, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G49108TO", "G02815KT", "G15664MX", "G23719VF", "G36379GD", "G57317CE", "G84349RE", "G92050GC", "G92275SC" ], "uniprot_id": "Q16849" }, "relationship_type": "biomarker", "source_pmcid": "PMC12296425" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation is essential for DEP-1 function in cell signaling.", "mechanism": "DEP-1 acts as a tumor suppressor; glycosylation modulates its phosphatase activity and cell surface expression.", "protein": "DEP-1 (Density-enhanced phosphatase-1)", "protein_enriched": { "function": "Plays a role in vesicle-mediated secretory processes (PubMed:24843546). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity). Required", "gene_name": "PTPRN", "glycan_count": 11, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G49108TO", "G02815KT", "G15664MX", "G23719VF", "G36379GD", "G57317CE", "G84349RE", "G92050GC", "G92275SC" ], "uniprot_id": "Q16849" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12296425" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation required for proper folding and signaling.", "mechanism": "Insulin receptor glycosylation is critical for receptor function and insulin sensitivity.", "protein": "Insulin Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12296425" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "N-linked glycosylation required for proper folding and function.", "mechanism": "Mediates viral entry and fusion with host cell membrane, enabling infection.", "protein": "Gc glycoprotein (Schmallenberg virus)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12297138" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "N-linked glycosylation involved in folding and trafficking.", "mechanism": "Forms heterodimer with Gc, required for viral attachment and entry.", "protein": "Gn glycoprotein (Schmallenberg virus)", "relationship_type": "causal", "source_pmcid": "PMC12297138" }, { "confidence": "high", "disease": "Congenital malformations in ruminants", "glycan_involvement": "Glycosylation supports infectivity and tropism.", "mechanism": "Facilitates infection of pregnant livestock, leading to fetal infection and malformations.", "protein": "Gc glycoprotein (Schmallenberg virus)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12297138" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Targeting glycosylated regions may enhance specificity.", "mechanism": "Peptides derived from Gc domains inhibit viral entry by blocking fusion.", "protein": "Gc glycoprotein (Schmallenberg virus)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "medium", "disease": "Rift Valley fever", "glycan_involvement": "Glycosylation may affect peptide binding and inhibition.", "mechanism": "Peptides modeled on fusion stem inhibit viral entry and cross-inhibit other viruses.", "protein": "Gc glycoprotein (Rift Valley fever virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "Glycosylation influences antigenicity and fusion activity.", "mechanism": "Stem-derived peptides inhibit viral entry by blocking fusion.", "protein": "E glycoprotein (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates immune recognition and fusion.", "mechanism": "Enfuvirtide peptide mimics gp41 helix, blocks fusion and viral entry.", "protein": "gp41 (HIV-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "medium", "disease": "Herpes simplex", "glycan_involvement": "Glycosylation affects structure and fusion activity.", "mechanism": "Peptides derived from gB inhibit viral entry.", "protein": "gB glycoprotein (Herpes simplex virus 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "medium", "disease": "Hantavirus infection", "glycan_involvement": "Glycosylation may stabilize fusion loops.", "mechanism": "Fusion loop peptides inhibit transition to post-fusion conformation.", "protein": "Gc glycoprotein (Hantavirus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "low", "disease": "Oropouche fever", "glycan_involvement": "Glycosylation may affect peptide binding.", "mechanism": "Potential for cross-inhibition by SBV Gc-derived peptides.", "protein": "Gc glycoprotein (Oropouche virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12297138" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation is essential for secretion and stability; glycan structure may affect biomarker utility.", "mechanism": "Regulates inflammation, tissue remodeling, and fibrosis; levels unexpectedly decreased in DN patients in this study.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation required for function and detection in serum.", "mechanism": "Elevated plasma levels in T2DM; associated with inflammation and disease progression.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects stability and detection.", "mechanism": "Elevated serum levels found in cardiovascular disease; reflects chronic inflammation.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation impacts secretion and function.", "mechanism": "Elevated in several cancers; involved in tissue remodeling and fibrosis.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation required for extracellular activity.", "mechanism": "May contribute to DN development via m6A methylation-associated gene expression and M1 macrophage infiltration.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "causal", "source_pmcid": "PMC12298235" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation affects serum stability and detection.", "mechanism": "Serum levels positively correlated with GFR and negatively with BUN; may reflect chronic phase of inflammation.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Not applicable (not a glycoprotein).", "mechanism": "Serum MaR1 levels elevated in DN; positively correlated with CRP, BUN, creatinine, negatively with GFR.", "protein": "Maresin 1 (MaR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12298235" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Not applicable.", "mechanism": "Anti-inflammatory and anti-fibrotic effects; increases in response to kidney injury as a compensatory mechanism.", "protein": "Maresin 1 (MaR1)", "relationship_type": "protective", "source_pmcid": "PMC12298235" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation required for extracellular function.", "mechanism": "Involved in inflammation and fibrosis underlying diabetic complications.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "causal", "source_pmcid": "PMC12298235" }, { "confidence": "low", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation may affect therapeutic targeting.", "mechanism": "Potential target due to role in inflammation and fibrosis; further research needed.", "protein": "CHI3L1 (Chitinase-3-like protein 1)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12298235" }, { "confidence": "high", "disease": "Multidrug-resistant cancer", "glycan_involvement": "P-glycoprotein is a glycosylated membrane protein; glycosylation is required for proper folding and membrane localization.", "mechanism": "Overexpression of P-glycoprotein mediates efflux of chemotherapeutic drugs, leading to multidrug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12300152" }, { "confidence": "high", "disease": "Breast carcinoma", "glycan_involvement": "Glycosylation supports surface expression and function.", "mechanism": "P-glycoprotein expression correlates with poor response to paclitaxel and doxorubicin in breast carcinoma samples.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12300152" }, { "confidence": "high", "disease": "Adult acute leukemia", "glycan_involvement": "Glycosylation is necessary for drug efflux activity.", "mechanism": "P-glycoprotein levels correlate with in vitro sensitivity to daunorubicin and clinical outcomes.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12300152" }, { "confidence": "high", "disease": "Uterine sarcoma", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Drug-selected MES-SA/Dx5 uterine sarcoma cells overexpress P-glycoprotein, conferring resistance to doxorubicin, paclitaxel, and vinblastine.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12300152" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation supports surface expression and drug efflux.", "mechanism": "Retrovirally transfected MDA435/LCC6 MDR1 melanoma cells overexpress P-glycoprotein, resulting in resistance to multiple chemotherapeutics.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12300152" }, { "confidence": "high", "disease": "Multidrug-resistant cancer", "glycan_involvement": "Targeting glycosylated P-gp on the membrane is essential for therapeutic efficacy.", "mechanism": "siRNA-mediated knockdown of P-glycoprotein restores drug sensitivity in resistant cancer cell lines.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. 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"source_pmcid": "PMC12301219" }, { "confidence": "medium", "disease": "Pulmonary congestion", "glycan_involvement": "Fc glycosylation supports in vivo stability.", "mechanism": "Reduces pulmonary congestion post-MI, possibly via improved cardiac function and lymphangiogenesis.", "protein": "Fc-ELA-21 fusion protein", "relationship_type": "therapeutic", "source_pmcid": "PMC12301219" }, { "confidence": "high", "disease": "Renal and liver toxicity", "glycan_involvement": "Glycosylation reduces immunogenicity and toxicity.", "mechanism": "No observed toxicity in liver or kidney at therapeutic doses.", "protein": "Fc-ELA-21 fusion protein", "relationship_type": "protective", "source_pmcid": "PMC12301219" }, { "confidence": "high", "disease": "Heart failure (systolic)", "glycan_involvement": "APJ is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "Activation by ELA or Fc-ELA-21 improves cardiac contractility.", "protein": "APJ receptor", "protein_enriched": { "function": "Can mediate aggregation most likely through a homophilic molecular interaction", "gene_name": "ESAM", "glycan_count": 28, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05049YU", "G08918WF", "G11314AS", "G18647XP", "G22310AV", "G27058EU", "G30221QT", "G47644PP", "G57888GL", "G59924QI", "G63980BQ", "G70619PT", "G83460ZZ", "G84452RH", "G85269DF", "G90659AW", "G95865ZB", "G01650EU", "G31852PQ", "G37399XV", "G41840AI", "G47702MW", "G52527GH", "G59536GA", "G63041LO", "G81263BG", "G33791AF" ], "uniprot_id": "Q96AP7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12301219" }, { "confidence": "high", "disease": "Heart failure (systolic)", "glycan_involvement": "VEGFR3 is N-glycosylated, essential for receptor function.", "mechanism": "Activation promotes lymphangiogenesis and endothelial proliferation, aiding cardiac recovery.", "protein": "VEGFR3", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiova", "gene_name": "FLT4", "glycan_count": 5, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G03579TP", "G80920RR", "G45395BF", "G25952OG", "G83460ZZ" ], "uniprot_id": "P35916" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12301219" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Fc glycosylation supports therapeutic use.", "mechanism": "Exogenous ELA improves hypertension and proteinuria in ELA knockout mice.", "protein": "Fc-ELA-21 fusion protein", "relationship_type": "protective", "source_pmcid": "PMC12301219" }, { "confidence": "medium", "disease": "Pulmonary arterial hypertension (PAH)", "glycan_involvement": "Fc glycosylation enhances half-life.", "mechanism": "ELA administration reduces right ventricular pressure and hypertrophy in PAH models.", "protein": "Fc-ELA-21 fusion protein", "relationship_type": "therapeutic", "source_pmcid": "PMC12301219" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may regulate receptor function.", "mechanism": "APJ signaling modulates cardiovascular pathology.", "protein": "APJ receptor", "protein_enriched": { "function": "Can mediate aggregation most likely through a homophilic molecular interaction", "gene_name": "ESAM", "glycan_count": 28, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05049YU", "G08918WF", "G11314AS", "G18647XP", "G22310AV", "G27058EU", "G30221QT", "G47644PP", "G57888GL", "G59924QI", "G63980BQ", "G70619PT", "G83460ZZ", "G84452RH", "G85269DF", "G90659AW", "G95865ZB", "G01650EU", "G31852PQ", "G37399XV", "G41840AI", "G47702MW", "G52527GH", "G59536GA", "G63041LO", "G81263BG", "G33791AF" ], "uniprot_id": "Q96AP7" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12301219" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation required for VEGFR3 activity.", "mechanism": "VEGFR3 activation improves lymphatic function, reducing edema and improving cardiac healing.", "protein": "VEGFR3", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiova", "gene_name": "FLT4", "glycan_count": 5, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G03579TP", "G80920RR", "G45395BF", "G25952OG", "G83460ZZ" ], "uniprot_id": "P35916" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12301219" }, { "confidence": "high", "disease": "Hepatitis C virus infection", "glycan_involvement": "Grp94 assists folding of glycosylated E2; glycosylation critical for function.", "mechanism": "Grp94 chaperones HCV E2 glycoprotein, promoting viral replication and anti-apoptotic signaling via NF-\u03baB activation.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "Dengue virus infection", "glycan_involvement": "Grp94 chaperones viral glycoproteins; glycosylation required for maturation.", "mechanism": "Grp94 is essential for DENV2 glycoprotein folding and replication via ERAD; knockdown inhibits viral replication.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "Chaperones glycosylated viral proteins.", "mechanism": "Grp94 supports Zika glycoprotein folding and replication through ERAD; inhibition blocks replication.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Grp94 influences glycosylated ACE2 and spike protein maturation.", "mechanism": "Grp94 regulates cell surface ACE2 and furin, facilitating spike protein-mediated entry; knockdown reduces viral entry.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "medium", "disease": "Herpes simplex virus 1 infection", "glycan_involvement": "Grp94 chaperones glycosylated gB.", "mechanism": "Grp94 interacts with HSV-1 gB glycoprotein, promoting viral entry and fusion.", "protein": "Grp94/gp96", "relationship_type": "causal", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "Human Herpesvirus 6 infection", "glycan_involvement": "Grp94 interacts with glycosylated viral glycoproteins.", "mechanism": "Grp94 binds HHV-6 glycoprotein Q1, facilitating receptor-mediated entry; knockdown inhibits infection.", "protein": "Grp94/gp96", "relationship_type": "causal", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "Grp94 chaperones glycosylated polymerase.", "mechanism": "Grp94 stabilizes HBV polymerase and promotes replication; elevated in HBV-induced liver disease.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "medium", "disease": "Senecavirus A infection", "glycan_involvement": "Indirect, via chaperoning glycoproteins.", "mechanism": "Grp94 promotes SVA replication by enhancing ER stress-induced autophagy; inhibition suppresses replication.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "medium", "disease": "Metastatic cancer", "glycan_involvement": "Grp94 chaperones glycosylated client proteins.", "mechanism": "Grp94 supports folding of oncogenic glycoproteins; inhibition is non-toxic and therapeutic.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "medium", "disease": "Primary open-angle glaucoma", "glycan_involvement": "Grp94 chaperones glycosylated proteins involved in ocular homeostasis.", "mechanism": "Grp94 implicated in disease pathogenesis; selective inhibition proposed as therapy.", "protein": "Grp94/gp96", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12302985" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Aberrant glycosylation modulates mTOR stability and activity, influencing cell death.", "mechanism": "Hyperactivation of mTOR promotes VSMC proliferation, endothelial dysfunction, and foam cell apoptosis, destabilizing plaques.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "causal", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Ischemia-Reperfusion Injury", "glycan_involvement": "Glycosylation alters Raptor-mTOR interaction, modulating autophagy.", "mechanism": "Acetylation and glycosylation of Raptor regulate mTORC1 activity, affecting cardiomyocyte autophagy and necrosis.", "protein": "Raptor", "protein_enriched": { "function": "Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote ce", "gene_name": "RPTOR", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q8N122" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation affects TSC2 stability and mTOR inhibition.", "mechanism": "SUMOylation and glycosylation of TSC2 enhance mTOR activity, worsening oxidative stress and apoptosis.", "protein": "TSC2", "protein_enriched": { "function": "Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulate", "gene_name": "TSC2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G53434XO", "G49108TO" ], "uniprot_id": "P49815" }, "relationship_type": "causal", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates S6K1 activation and downstream signaling.", "mechanism": "Phosphorylation and glycosylation of S6K1 drive endothelial dysfunction and VSMC phenotypic switching.", "protein": "S6K1", "protein_enriched": { "function": "Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:1150036", "gene_name": "RPS6KB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23443" }, "relationship_type": "biomarker", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation regulates 4EBP1 stability and translation control.", "mechanism": "Hyperphosphorylation and glycosylation of 4EBP1 contribute to maladaptive hypertrophy and fibrosis.", "protein": "4EBP1", "protein_enriched": { "function": "Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, le", "gene_name": "EIF4EBP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13541" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "Glycosylation affects Akt localization and activity.", "mechanism": "mTORC2-mediated phosphorylation and glycosylation of Akt promote endothelial dysfunction and inflammation.", "protein": "Akt", "protein_enriched": { "function": "AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, gro", "gene_name": "Akt1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47196" }, "relationship_type": "causal", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates FBXW7 substrate recognition.", "mechanism": "FBXW7-mediated ubiquitination and glycosylation of mTORC1 components regulate macrophage apoptosis, stabilizing plaques.", "protein": "FBXW7", "protein_enriched": { "function": "Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubM", "gene_name": "FBXW7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969H0" }, "relationship_type": "protective", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation influences TRAF6 signaling output.", "mechanism": "K63-linked ubiquitination and glycosylation of TRAF6 activate mTORC1 and NF-\u03baB, amplifying inflammation and cell death.", "protein": "TRAF6", "relationship_type": "causal", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Glycosylation stabilizes USP9X-mTOR interaction.", "mechanism": "USP9X deubiquitinates and glycosylates mTOR, suppressing cell death and improving cardiac function.", "protein": "USP9X", "protein_enriched": { "function": "Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (PubMed:18254724, PubMed:19135894, PubMed:22371489, PubMed:25944111, PubMed:29626158, PubMed:309144", "gene_name": "USP9X", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q93008" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12303995" }, { "confidence": "medium", "disease": "Ischemia-Reperfusion Injury", "glycan_involvement": "Glycosylation modulates SIRT1 activity and substrate specificity.", "mechanism": "SIRT1-mediated deacetylation and glycosylation restore mitochondrial function and reduce apoptosis.", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12303995" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Increased N-glycosylation in variable domain correlates with disease-specific autoantibody production.", "mechanism": "Elevated variable domain glycans (VDGs) are a hallmark of RA-specific autoantibodies.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "VDGs modulate BCR signaling and reduce complement activation, affecting immune complex clearance.", "mechanism": "ACPA with high VDGs may promote autoreactive B cell survival and persistence.", "protein": "Anticitrullinated protein antibody (ACPA)", "relationship_type": "causal", "source_pmcid": "PMC12305304" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "N-glycosylation in variable domain is associated with autoantibody diversity.", "mechanism": "Elevated VDGs detected on autoantibodies in SLE patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "medium", "disease": "Antineutrophil cytoplasmic antibody\u2013associated vasculitis", "glycan_involvement": "N-glycosylation in variable domain marks disease-associated antibodies.", "mechanism": "High VDGs found on autoantibodies in vasculitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "medium", "disease": "Pemphigus vulgaris", "glycan_involvement": "N-glycosylation in variable domain is increased.", "mechanism": "Autoantibodies in pemphigus vulgaris show elevated VDGs.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "medium", "disease": "Myasthenia gravis", "glycan_involvement": "N-glycosylation in variable domain is elevated.", "mechanism": "Autoantibodies in myasthenia gravis have increased VDGs.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "high", "disease": "Immunogenicity to biologics (e.g., adalimumab/infliximab)", "glycan_involvement": "N-glycosylation in variable domain is common in antidrug antibodies.", "mechanism": "Antidrug antibodies with high VDGs emerge in patients treated with biologics.", "protein": "Antidrug antibody (anti-adalimumab)", "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation in variable domain impairs IgG hexamerization and C1q binding.", "mechanism": "VDGs on IgG inhibit classical complement activation, potentially reducing inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12305304" }, { "confidence": "high", "disease": "Autoimmune diseases (general)", "glycan_involvement": "N-glycosylation in variable domain increases antibody diversity and modulates effector functions.", "mechanism": "Elevated VDGs are a common feature of autoantibodies in multiple autoimmune diseases.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12305304" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation in variable domain reduces complement activation and immune complex removal.", "mechanism": "VDGs may impair immune complex clearance, promoting autoantibody persistence and disease progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12305304" }, { "confidence": "high", "disease": "Hypertrophic nail dystrophy", "glycan_involvement": "O-glycosylation affects keratin filament assembly and immune function.", "mechanism": "Mutations or downregulation of KRT16 disrupt nail structure and immune checkpoint function.", "protein": "KRT16", "protein_enriched": { "function": "Epidermis-specific type I keratin that plays a key role in skin. Acts as a regulator of innate immunity in response to skin barrier breach: required for some inflammatory checkpoint for the skin barri", "gene_name": "KRT16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08779" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "medium", "disease": "Thickening of the skin", "glycan_involvement": "O-glycosylation modulates keratin filament stability.", "mechanism": "KRT5 stabilizes basal keratin cytoskeleton; downregulation leads to skin barrier defects.", "protein": "KRT5", "protein_enriched": { "function": "Required for the formation of keratin intermediate filaments in the basal epidermis and maintenance of the skin barrier in response to mechanical stress (By similarity). Regulates the recruitment of L", "gene_name": "KRT5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13647" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "medium", "disease": "Thickening of the skin", "glycan_involvement": "O-glycosylation regulates keratinocyte activation.", "mechanism": "KRT2 is essential for epidermal barrier; downregulation impairs cornification.", "protein": "KRT2", "protein_enriched": { "function": "Probably contributes to terminal cornification (PubMed:1380918). Associated with keratinocyte activation, proliferation and keratinization (PubMed:12598329). Required for maintenance of corneocytes an", "gene_name": "KRT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35908" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "medium", "disease": "Thickening of the skin", "glycan_involvement": "O-glycosylation affects filament assembly.", "mechanism": "KRT9 mutations cause abnormal keratin filament assembly and skin thickening.", "protein": "KRT9", "protein_enriched": { "function": "May serve an important special function either in the mature palmar and plantar skin tissue or in the morphogenetic program of the formation of these tissues. Plays a role in keratin filament assembly", "gene_name": "KRT9", "glycan_count": 13, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41882MT", "G10019LZ", "G11629QQ", "G34617SM", "G37881RL", "G38663NM", "G39595FH", "G43089EG", "G47748JZ", "G52527GH", "G56784JY", "G57888GL", "G49108TO" ], "uniprot_id": "P35527" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "medium", "disease": "Deafness", "glycan_involvement": "Potential N-glycosylation modulates protein stability.", "mechanism": "MYH14 mutations or dysregulation impact cochlear function.", "protein": "MYH14", "protein_enriched": { "function": "Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping", "gene_name": "MYH14", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q7Z406" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "medium", "disease": "Peripheral neuropathy with myopathy, hoarseness, hearing loss", "glycan_involvement": "Possible N-glycosylation involvement.", "mechanism": "MYH14 dysregulation affects muscle and nerve function.", "protein": "MYH14", "protein_enriched": { "function": "Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping", "gene_name": "MYH14", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q7Z406" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "high", "disease": "GLUT1 deficiency syndrome", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Defective glucose transport leads to neurological symptoms.", "protein": "GTR1 (SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "high", "disease": "Emery-Dreifuss muscular dystrophy (EDMD)", "glycan_involvement": "Emerin is a glycoprotein; glycosylation affects nuclear envelope integrity.", "mechanism": "Emerin mutations cause nuclear envelope defects and muscle dystrophy.", "protein": "Emerin", "protein_enriched": { "function": "Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-caten", "gene_name": "EMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G40834TG" ], "uniprot_id": "P50402" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "O-mannosylation critical for function.", "mechanism": "Defective glycosylation of dystroglycan impairs muscle membrane stability.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12306095" }, { "confidence": "low", "disease": "Lipodystrophy", "glycan_involvement": "Unknown.", "mechanism": "PLN1 dysregulation associated with abnormal lipid metabolism.", "protein": "PLN1", "relationship_type": "biomarker", "source_pmcid": "PMC12306095" }, { "confidence": "high", "disease": "Escherichia coli infection", "glycan_involvement": "Lectin domain binds \u03b2-galactosides on bacteria.", "mechanism": "Upregulated galectin binds bacterial glycans, enhancing pathogen recognition and clearance.", "protein": "Galectin", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Escherichia coli infection", "glycan_involvement": "Potential O-glycosylation modulates membrane association.", "mechanism": "Annexin upregulation stabilizes membrane and modulates inflammation during infection.", "protein": "Annexin", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Skin lesions", "glycan_involvement": "O-glycosylation may affect filament assembly.", "mechanism": "Upregulated keratin reinforces epithelial barrier against bacterial invasion.", "protein": "Keratin, type I cytoskeletal 19-like", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Antibiotic resistance", "glycan_involvement": "N-glycosylation influences lipid binding and immune function.", "mechanism": "Upregulated apolipoprotein A-Ib may bind and neutralize bacterial LPS.", "protein": "Apolipoprotein A-Ib", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Escherichia coli infection", "glycan_involvement": "Removes N-glycans from glycoproteins, modulating immune response.", "mechanism": "Upregulation suggests increased glycan remodeling during infection.", "protein": "Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase", "relationship_type": "biomarker", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Escherichia coli infection", "glycan_involvement": "Binds mannose-rich glycans on bacteria.", "mechanism": "Downregulation may reduce pathogen recognition capacity.", "protein": "C-type lectin domain-containing protein", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Skin lesions", "glycan_involvement": "N-glycosylation stabilizes protein and regulates activity.", "mechanism": "Downregulation may impair protease inhibition, increasing tissue damage.", "protein": "Alpha-1-antitrypsin homolog", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "high", "disease": "Escherichia coli infection", "glycan_involvement": "Glycosylation affects stability and antimicrobial function.", "mechanism": "Downregulation reduces bactericidal activity in mucus.", "protein": "Lysozyme C-like", "relationship_type": "protective", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Hemorrhaging", "glycan_involvement": "N-glycosylation required for clot formation.", "mechanism": "Downregulation may contribute to impaired coagulation and bleeding.", "protein": "Fibrinogen gamma chain", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0G7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12311534" }, { "confidence": "medium", "disease": "Skin lesions", "glycan_involvement": "N-glycosylation modulates cytokine secretion.", "mechanism": "Downregulation may dampen inflammatory response to infection.", "protein": "Interleukin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12311534" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "EPO is a heavily glycosylated hormone; glycosylation is essential for stability and activity.", "mechanism": "EPO exerts neuroprotective effects (antioxidant, anti-apoptotic, anti-inflammatory) in animal models of PD.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Clusterin is a glycoprotein; glycosylation affects secretion and chaperone function.", "mechanism": "Clusterin neutralizes misfolded proteins and clears amyloid-\u03b2 fibrils; genetic variants linked to cognitive decline.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12316016" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation modulates clusterin's stability and function in kidney tissue.", "mechanism": "Increased clusterin expression in CKD leads to defensive inflammatory response and oxidative stress.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "APOE glycosylation affects lipid binding and amyloid-\u03b2 interaction.", "mechanism": "APOE regulates amyloid-\u03b2 clearance; \u03b54 allele increases AD risk.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12316016" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation influences SORT1 trafficking and receptor function.", "mechanism": "SORT1 is a cardiovascular risk factor in CKD; regulates protein sorting.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "SORL1 glycosylation modulates receptor activity and APP processing.", "mechanism": "SORL1 regulates APP trafficking and amyloid-\u03b2 production; variants increase AD risk.", "protein": "SORL1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Collagen glycosylation affects matrix assembly and cell interactions.", "mechanism": "Type IV collagen gene variants contribute to glomerular disorders.", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC12316016" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation modulates collagen's interaction with CNS cells.", "mechanism": "Increased type IV collagen from astrocytes inhibits axon repair and promotes immune cell migration.", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation may affect LRRK2 localization and function.", "mechanism": "LRRK2 mutations are linked to late-onset PD; expressed in kidney and brain.", "protein": "Leucine-rich repeat kinase 2 (LRRK2)", "protein_enriched": { "function": "Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:1", "gene_name": "LRRK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q5S007" }, "relationship_type": "causal", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "APP glycosylation regulates processing and amyloid-\u03b2 production.", "mechanism": "APP processing generates amyloid-\u03b2 peptides; impaired clearance in CKD may exacerbate AD.", "protein": "Amyloid-\u03b2 precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12316016" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "Fucosylated, monosialylated N-glycan with bisecting GlcNAc enhances pathogenicity.", "mechanism": "Anti-MAG IgM with unique N-glycosylation binds MAG and activates complement, leading to demyelination.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "Distinct N-glycan profile (peak 12) is disease-associated.", "mechanism": "N-glycosylation and C1q binding of anti-MAG IgM can serve as biomarkers for disease monitoring.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12316464" }, { "confidence": "medium", "disease": "Anti-MAG neuropathy", "glycan_involvement": "Sialylation and N-glycan structure modulate complement activation.", "mechanism": "Targeting IgM glycosylation or its complement activation may provide therapeutic benefit.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "N-glycans required for cytokine induction; deglycosylation reduces effect.", "mechanism": "Glycosylated anti-MAG IgM induces proinflammatory cytokine production (IL-1, IL-6, IL-8, TNF-\u03b1, IFN-\u03b3) by macrophages.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "medium", "disease": "Anti-MAG neuropathy", "glycan_involvement": "N-glycan-dependent induction of IL-8.", "mechanism": "IL-8 upregulation by glycosylated anti-MAG IgM suggests IL-8 pathway as a therapeutic target.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "Sialylation critical for MAG and C1q binding.", "mechanism": "Sialylated N-glycans on anti-MAG IgM enhance binding to MAG and C1q, promoting disease.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "medium", "disease": "Anti-MAG neuropathy", "glycan_involvement": "N-glycan profile enhances receptor binding.", "mechanism": "Anti-MAG IgM binds more strongly to Fc\u03b1/\u03bcR and DC-SIGN, potentially activating macrophages.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "IgM sialylation increases C1q binding.", "mechanism": "C1q binding by glycosylated anti-MAG IgM activates classical complement pathway, leading to nerve damage.", "protein": "C1q complement protein", "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "MAG's own glycosylation (HNK-1 epitope) is the IgM target.", "mechanism": "MAG is targeted by anti-MAG IgM, leading to demyelination.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Chronic demyelinating neuropathy", "glycan_involvement": "N-glycan-dependent complement activation.", "mechanism": "Anti-MAG IgM deposits and complement activation cause demyelination.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC12316464" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy type 1A (MDC1A)", "glycan_involvement": "Laminin is a glycoprotein; glycosylation is essential for its structural stability and interactions.", "mechanism": "Mutations in LAMA2 disrupt laminin-\u03b12 function, impairing muscle fiber-matrix connection and leading to muscle weakness and degeneration.", "protein": "Laminin subunit alpha-2 (LAMA2)", "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Merosin-deficient CMD type 1D", "glycan_involvement": "O-mannosyl glycosylation of \u03b1-DG is critical for function; mutations in glycosyltransferases cause disease.", "mechanism": "Defective glycosylation of \u03b1-DG impairs its binding to extracellular matrix, destabilizing muscle cell membranes.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "medium", "disease": "Congenital muscular dystrophy (CMD)", "glycan_involvement": "Collagen VI is a glycoprotein; glycosylation affects its assembly and function.", "mechanism": "Mutations in collagen VI genes disrupt extracellular matrix stability, leading to muscle weakness.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "medium", "disease": "Myositis", "glycan_involvement": "MHC-I is a glycoprotein; glycosylation modulates immune recognition.", "mechanism": "Upregulation of MHC-I in muscle fibers is associated with immune activation and inflammation.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12316597" }, { "confidence": "medium", "disease": "Myositis", "glycan_involvement": "CD68 is a glycoprotein; glycosylation affects its function in immune cells.", "mechanism": "High CD68 expression indicates macrophage infiltration and muscle inflammation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12316597" }, { "confidence": "medium", "disease": "Merosin-deficient congenital muscular dystrophy type 1A (MDC1A)", "glycan_involvement": "Integrins are glycoproteins; glycosylation modulates ligand binding.", "mechanism": "Loss of LAMA2-integrin \u03b17\u03b21 interaction impairs muscle cell adhesion and signaling.", "protein": "Integrin \u03b17\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Merosin-deficient CMD type 1D", "glycan_involvement": "FKRP is a glycosyltransferase essential for O-mannosyl glycan synthesis on \u03b1-DG.", "mechanism": "FKRP mutations impair glycosylation of \u03b1-DG, leading to defective muscle membrane stability.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Merosin-deficient CMD type 1D", "glycan_involvement": "POMT1 is an O-mannosyltransferase for \u03b1-DG glycosylation.", "mechanism": "POMT1 mutations disrupt O-mannosylation of \u03b1-DG, causing CMD.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Merosin-deficient CMD type 1D", "glycan_involvement": "POMT2 is an O-mannosyltransferase for \u03b1-DG glycosylation.", "mechanism": "POMT2 mutations disrupt O-mannosylation of \u03b1-DG, causing CMD.", "protein": "POMT2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G72747WU", "G83460ZZ", "G02815KT", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G70101JE", "G64527OM" ], "uniprot_id": "Q9UKY4" }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Merosin-deficient CMD type 1D", "glycan_involvement": "LARGE1 is a glycosyltransferase for \u03b1-DG O-mannosyl glycan elongation.", "mechanism": "LARGE1 mutations impair glycan extension on \u03b1-DG, leading to CMD.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC12316597" }, { "confidence": "high", "disease": "Aging/Inflammaging", "glycan_involvement": "Altered N-glycosylation patterns drive inflammaging.", "mechanism": "IgG glycosylation changes (\u2193galactosylation, \u2193sialylation, \u2191bisecting GlcNAc) promote pro-inflammatory responses and track biological age.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Specific N-glycan structures predict disease risk.", "mechanism": "Mono/di-galactosylated IgG glycans and reduced bisecting GlcNAc are negatively associated with incident diabetes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycan composition reflects inflammatory status and risk.", "mechanism": "Mono/di-galactosylated IgG glycans and reduced bisecting GlcNAc are negatively associated with incident CVD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "medium", "disease": "Type 1 Diabetes", "glycan_involvement": "Unprocessed N-glycans trigger unfolded protein response and ER stress.", "mechanism": "High-mannose and glucosylated C3 glycans (e.g., GlcNAc2Man9Glc1) are increased in T1D and renal complications, linked to ER stress.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "high", "disease": "Metabolic Syndrome", "glycan_involvement": "C3 glycosylation status reflects metabolic health.", "mechanism": "Elevated C3 protein levels are associated with adiposity, dyslipidemia, insulin resistance, and liver dysfunction.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "medium", "disease": "Longevity", "glycan_involvement": "Reduced C3 and altered glycoforms may promote healthy aging.", "mechanism": "Lower C3 plasma concentrations are associated with longevity in centenarians.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "protective", "source_pmcid": "PMC12316861" }, { "confidence": "high", "disease": "Chronic Inflammatory Disease", "glycan_involvement": "N-glycan branching and sialylation drive inflammatory processes.", "mechanism": "High-branched and highly sialylated plasma N-glycans are increased in chronic inflammation.", "protein": "Plasma proteins (total)", "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "high", "disease": "Aging/Inflammaging", "glycan_involvement": "Loss of galactose/sialic acid marks biological aging.", "mechanism": "Agalactosylation and asialylation signatures in plasma glycome are hallmarks of aging.", "protein": "Plasma proteins (total)", "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "medium", "disease": "Autoimmune Disease", "glycan_involvement": "Modified N-glycosylation alters IgG effector function.", "mechanism": "Glyco-engineered IgG with increased galactosylation/sialylation may have anti-inflammatory and anti-autoimmune effects.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12316861" }, { "confidence": "medium", "disease": "Renal Complications of Diabetes", "glycan_involvement": "ER stress-related glycoforms reflect disease state.", "mechanism": "Increased high-mannose/glucosylated C3 glycoforms are associated with diabetic renal complications.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12316861" }, { "confidence": "medium", "disease": "Immune disorders", "glycan_involvement": "Sialylation patterns on glycoRNA fine-tune immune signaling.", "mechanism": "Sialylated glycoRNA interacts with Siglec receptors, modulating immune responses.", "protein": "GlycoRNA", "relationship_type": "causal", "source_pmcid": "PMC12317082" }, { "confidence": "medium", "disease": "Host-microbiota interaction disorders", "glycan_involvement": "Tissue-specific glycan enrichment in colon may mediate host-microbiota crosstalk.", "mechanism": "Colon-specific glycoRNA glycan features suggest a role in microbiota interactions.", "protein": "GlycoRNA", "relationship_type": "causal", "source_pmcid": "PMC12317082" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Altered N-glycan profiles serve as cancer biomarkers.", "mechanism": "Aberrant glycosylation patterns are linked to cancer initiation and progression.", "protein": "Human serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12317082" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Altered glycan structures reflect disease state.", "mechanism": "Changes in glycosylation are associated with diabetes progression.", "protein": "Human serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12317082" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Altered glycan patterns observed in Alzheimer\u2019s.", "mechanism": "Glycosylation changes influence protein function in neurodegeneration.", "protein": "Human serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12317082" }, { "confidence": "high", "disease": "Colorectal carcinoma", "glycan_involvement": "Loss of fucosylation in HCT116 cells impacts glycan profile and disease phenotype.", "mechanism": "GMD mutation blocks fucosylation, affecting glycan-mediated cell signaling.", "protein": "GDP-mannose-4,6-dehydratase (GMD)", "protein_enriched": { "function": "Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum prot", "gene_name": "SEL1L", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G05724UK", "G08290VR", "G10819WX", "G26377UA", "G27947YN", "G31852PQ", "G40574BA", "G40926MX", "G41272YH", "G46691LC", "G47702MW", "G51653BI", "G58087IP", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G70101JE", "G70441OD", "G72747WU", "G79666IR", "G80075MS", "G80920RR", "G86880BF", "G87123QX", "G06110VR", "G27058EU", "G39188ZX", "G14260UH", "G48584BU", "G49108TO", "G57321FI", "G05049YU", "G15664MX", "G25079LO", "G41247ZX", "G46503DX", "G46687AB", "G49642SA", "G49874UX", "G54010QB", "G58954YZ", "G66621EA", "G83460ZZ", "G90659AW", "G02815KT" ], "uniprot_id": "Q9UBV2" }, "relationship_type": "causal", "source_pmcid": "PMC12317082" }, { "confidence": "high", "disease": "Metastasis", "glycan_involvement": "Increased fucosylation correlates with metastatic potential.", "mechanism": "Fucosylation promotes cell adhesion and cancer metastasis.", "protein": "Fucosylated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12317082" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Altered abundance in disease states.", "mechanism": "Sialofucosylated glycans modulate inflammatory responses.", "protein": "Sialofucosylated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12317082" }, { "confidence": "medium", "disease": "Gastrointestinal diseases", "glycan_involvement": "O-GalNAc-linked glycans protect against GI disorders.", "mechanism": "O-glycosylation of mucins maintains gut barrier function.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12317082" }, { "confidence": "low", "disease": "Neurological diseases", "glycan_involvement": "Sialylated glycan ligands modulate Siglec signaling.", "mechanism": "Siglec-glycan interactions regulate neuroinflammation.", "protein": "Siglec receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12317082" }, { "confidence": "high", "disease": "Diabetes Mellitus (general)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin by glucose.", "mechanism": "Hemoglobin glycation (HbA1c) reflects chronic hyperglycemia in diabetes.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12317189" }, { "confidence": "high", "disease": "Diabetic Complications (AGE-related)", "glycan_involvement": "AGEs are formed via glycation of hemoglobin and other proteins.", "mechanism": "Glycated hemoglobin leads to formation of advanced glycation end products (AGEs), contributing to diabetic complications.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12317189" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Alpha-amylase is a glycoprotein; its activity affects carbohydrate metabolism.", "mechanism": "Inhibition of alpha-amylase reduces starch breakdown, lowering postprandial glucose spikes.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12317189" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Targeting glycation process of hemoglobin.", "mechanism": "Prevention of hemoglobin glycation reduces AGE formation and diabetic complications.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12317189" }, { "confidence": "high", "disease": "Diabetes Mellitus (general)", "glycan_involvement": "Enzyme acts on glycosidic bonds in starch.", "mechanism": "Alpha-amylase inhibition is a strategy for glycemic control in diabetes.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12317189" }, { "confidence": "medium", "disease": "Diabetes Mellitus (general)", "glycan_involvement": "Reduces non-enzymatic glycation of hemoglobin.", "mechanism": "Atriplex halimus extracts inhibit hemoglobin glycation, potentially reducing diabetes complications.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12317189" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Inhibition of glycoprotein enzyme activity.", "mechanism": "Atriplex halimus extracts inhibit alpha-amylase, lowering glucose absorption.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "protective", "source_pmcid": "PMC12317189" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "O-GlcNAcylation of proteins alters signaling and metabolic regulation.", "mechanism": "UDP-GlcNAc is substrate for O-GlcNAcylation; increased O-GlcNAc modification contributes to insulin resistance and diabetic complications.", "protein": "UDP-GlcNAc", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12318844" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "O-glycosylation (O-GlcNAc) at serine/threonine residues.", "mechanism": "Excessive O-GlcNAcylation impairs insulin signaling and vascular function.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12318844" }, { "confidence": "high", "disease": "Acute lung injury (ALI)/ARDS", "glycan_involvement": "P2Y6 is a glycosylated GPCR; glycosylation affects receptor function.", "mechanism": "UDP (uridine derivative) activates P2Y6, promoting inflammatory cytokine release and immune cell recruitment.", "protein": "P2Y6 receptor", "protein_enriched": { "function": "Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system", "gene_name": "P2RY6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q15077" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Regulates CAD, impacting pyrimidine/UDP-GlcNAc biosynthesis.", "mechanism": "XBP1 overexpression increases uridine synthesis and leptin, suppressing fat accumulation.", "protein": "XBP1", "protein_enriched": { "function": "Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic devel", "gene_name": "XBP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17861" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12318844" }, { "confidence": "high", "disease": "Cancer (lung adenocarcinoma)", "glycan_involvement": "Modulates uridine salvage, impacting glycan precursor pools.", "mechanism": "UPP1 upregulation drives glycolytic metabolism and enhances PD-L1 expression, promoting tumor progression.", "protein": "UPP1 (Uridine Phosphorylase 1)", "protein_enriched": { "function": "Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide", "gene_name": "UPP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16831" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Controls UDP-GlcNAc and other glycan precursor synthesis.", "mechanism": "UCK2 overexpression promotes malignant phenotype via pyrimidine salvage and nucleotide/glycan synthesis.", "protein": "UCK2 (Uridine-cytidine kinase 2)", "protein_enriched": { "function": "Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate (PubMed:11306702, PubMed:11494055). Does not phosphorylate deoxyribonucleosides or purine ribonucleosides (PubMe", "gene_name": "UCK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BZX2" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "FABP1 is glycosylated; glycosylation may affect lipid binding.", "mechanism": "Long-term uridine supply suppresses FABP1, contributing to hepatic lipid accumulation.", "protein": "FABP1", "protein_enriched": { "function": "Plays a role in lipoprotein-mediated cholesterol uptake in hepatocytes (PubMed:25732850). Binds cholesterol (PubMed:25732850). Binds free fatty acids and their coenzyme A derivatives, bilirubin, and s", "gene_name": "FABP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07148" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Cancer (lung metastasis)", "glycan_involvement": "UDP-glucose is a glycan donor; impacts glycosylation and signaling.", "mechanism": "UDP-glucose inhibits HuR-mediated stabilization of SNAI1 mRNA, suppressing metastasis.", "protein": "UDP-glucose", "relationship_type": "protective", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; supports membrane glycoprotein integrity.", "mechanism": "Uridine-derived CDP-choline promotes phosphatidylcholine synthesis, supporting synaptic membrane formation and function.", "protein": "CDP-choline", "relationship_type": "protective/therapeutic", "source_pmcid": "PMC12318844" }, { "confidence": "medium", "disease": "Organ fibrosis (liver, lung)", "glycan_involvement": "O-glycosylation (O-GlcNAc) regulates fibrotic gene expression.", "mechanism": "Uridine increases O-GlcNAcylation, modulating inflammatory and fibrotic signaling.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12318844" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation at Asn227 is required for full tumor suppressor activity.", "mechanism": "SBSPON acts as a tumor suppressor by inhibiting proliferation, migration, invasion, and EMT of bladder cancer cells.", "protein": "SBSPON", "relationship_type": "protective", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation status may affect SBSPON stability and function.", "mechanism": "Low SBSPON expression correlates with poor prognosis, advanced stage, and lymph node metastasis.", "protein": "SBSPON", "relationship_type": "biomarker", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation at Asn227 is necessary for SBSPON's anti-tumor effects.", "mechanism": "Restoring SBSPON expression inhibits tumor growth and progression in vitro and in vivo.", "protein": "SBSPON", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Cisplatin resistance in bladder cancer", "glycan_involvement": "N-glycosylation at Asn227 enhances SBSPON's ability to inhibit cisplatin resistance.", "mechanism": "SBSPON overexpression sensitizes bladder cancer cells to cisplatin by promoting ER stress-mediated apoptosis.", "protein": "SBSPON", "relationship_type": "protective", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Loss of glycosylated SBSPON removes protective effect.", "mechanism": "Genetic ablation of Sbspon in mice accelerates BBN-induced bladder cancer progression.", "protein": "SBSPON", "relationship_type": "causal", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation at Asn227 is required for SBSPON to inhibit HSPA5 membrane translocation.", "mechanism": "SBSPON binds HSPA5 in the ER, inhibits HSPA5 membrane translocation, and suppresses AKT/GSK-3\u03b2/\u03b2-catenin signaling.", "protein": "SBSPON", "relationship_type": "mechanistic", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Cisplatin resistance in bladder cancer", "glycan_involvement": "N-glycosylation at Asn227 is important for SBSPON's interaction with HSPA5.", "mechanism": "SBSPON interrupts HSPA5-PERK interaction, lowering threshold for ER stress-induced apoptosis during chemotherapy.", "protein": "SBSPON", "relationship_type": "mechanistic", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation status not directly addressed for HSPA5 in this study.", "mechanism": "HSPA5 upregulation and membrane translocation promote tumor progression via AKT and MAPK signaling.", "protein": "HSPA5", "relationship_type": "causal", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Cisplatin resistance in bladder cancer", "glycan_involvement": "Not specified.", "mechanism": "HSPA5 inhibits ER stress-mediated apoptosis, contributing to cisplatin resistance.", "protein": "HSPA5", "relationship_type": "causal", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Direct N-glycosylation at Asn227.", "mechanism": "SBSPON glycosylation at Asn227 is essential for its tumor suppressor function and inhibition of HSPA5 membrane translocation.", "protein": "SBSPON", "relationship_type": "mechanistic", "source_pmcid": "PMC12320502" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is O-glycosylated; glycosylation affects stability and membrane localization.", "mechanism": "Loss-of-function mutations in DMD gene prevent dystrophin expression, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Cardiac failure in DMD", "glycan_involvement": "O-glycosylation may influence dystrophin's interaction with glycoprotein complexes in heart muscle.", "mechanism": "Absence of dystrophin in cardiomyocytes causes cardiac dysfunction and failure.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restored glycosylation of dystrophin enables proper assembly of glycoprotein complexes.", "mechanism": "Gene therapy restoring full-length dystrophin expression reverses muscle and cardiac defects.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation critical for \u03b2-dystroglycan function and membrane localization.", "mechanism": "Loss of dystrophin leads to reduced \u03b2-dystroglycan at muscle membrane; restoration indicates therapeutic efficacy.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation required for sarcoglycan complex stability.", "mechanism": "\u03b3-sarcoglycan expression at myofiber periphery is restored with dystrophin gene therapy.", "protein": "\u03b3-sarcoglycan", "protein_enriched": { "function": "Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (By similarity). May serve as a universal non-classical progesterone receptor in the uterus (Probable)", "gene_name": "PGRMC2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15173" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321383" }, { "confidence": "medium", "disease": "Nemaline myopathy", "glycan_involvement": "Potential involvement of glycosylation in protein stability and muscle function.", "mechanism": "Multi-AAV strategies for large gene delivery may be applicable to nemaline myopathy (caused by large gene mutations).", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321383" }, { "confidence": "medium", "disease": "RYR1-related myopathy", "glycan_involvement": "Glycosylation may affect protein folding and function.", "mechanism": "Gene therapy approaches for large proteins like dystrophin may be extended to RYR1-related myopathies.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321383" }, { "confidence": "medium", "disease": "Stargardt disease", "glycan_involvement": "Glycosylation may influence ABCA4 trafficking and function.", "mechanism": "Dual AAV and split intein strategies used to restore ABCA4 protein in Stargardt disease.", "protein": "ABCA4", "protein_enriched": { "function": "Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) ", "gene_name": "ABCA4", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22768VO", "G49108TO" ], "uniprot_id": "P78363" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321383" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation essential for F8 secretion and activity.", "mechanism": "Split intein-mediated gene therapy restores F8 protein in hemophilia models.", "protein": "Factor VIII (F8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation supports dystrophin's structural role in muscle membrane integrity.", "mechanism": "Restored dystrophin expression protects muscle fibers from contraction-induced injury.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "protective", "source_pmcid": "PMC12321383" }, { "confidence": "high", "disease": "Anti-neurofascin 155 autoimmune nodopathy", "glycan_involvement": "NF155 is a glycoprotein; glycosylation is essential for its cell adhesion function and antibody recognition.", "mechanism": "IgG4 autoantibodies target NF155 at the paranodal region, disrupting axoglial junctions and leading to neuropathy.", "protein": "Neurofascin 155", "protein_enriched": { "function": "", "gene_name": "PHTF1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UMS5" }, "relationship_type": "causal", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Glycosylation affects neurofascin isoform localization and antibody binding.", "mechanism": "IgG4 autoantibodies against NF140/186 disrupt node/paranode integrity, causing neuropathy.", "protein": "Neurofascin 140/186", "relationship_type": "causal", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Contactin-1 is heavily glycosylated; glycans mediate cell-cell interactions and antibody accessibility.", "mechanism": "IgG4 autoantibodies against CNTN1 impair paranodal adhesion, leading to neuropathy.", "protein": "Contactin-1", "relationship_type": "causal", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Glycosylation modulates CASPR1 function and immune recognition.", "mechanism": "IgG4 autoantibodies against CASPR1 disrupt paranodal junctions, contributing to neuropathy.", "protein": "CASPR1", "relationship_type": "causal", "source_pmcid": "PMC12321972" }, { "confidence": "high", "disease": "Anti-neurofascin 155 autoimmune nodopathy", "glycan_involvement": "IgG4 is glycosylated; glycan structure affects effector function and immune complex formation.", "mechanism": "Predominance of IgG4 autoantibodies is a diagnostic marker for anti-NF155 AN and predicts poor IVIG response.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321972" }, { "confidence": "high", "disease": "Anti-neurofascin 155 autoimmune nodopathy", "glycan_involvement": "CD20 is glycosylated; glycosylation may affect antibody binding and cell surface expression.", "mechanism": "CD20 is targeted by monoclonal antibodies (ofatumumab, rituximab) to deplete B cells and reduce pathogenic autoantibodies.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation of NF155 influences antibody recognition and disease specificity.", "mechanism": "Anti-NF155 antibodies are found in a subset of CIDP, indicating a distinct clinical phenotype.", "protein": "Neurofascin 155", "protein_enriched": { "function": "", "gene_name": "PHTF1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UMS5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyneuropathy (CIDP)", "glycan_involvement": "IgG4 glycosylation modulates immune effector functions.", "mechanism": "IgG4 autoantibody predominance is associated with poor response to IVIG in CIDP.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321972" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "CD20 glycosylation may affect therapeutic antibody efficacy.", "mechanism": "CD20-targeting antibodies (ofatumumab) deplete B cells, reducing autoimmune activity in MS.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12321972" }, { "confidence": "low", "disease": "Guillain-Barr\u00e9 Syndrome (GBS)", "glycan_involvement": "Glycosylation status may influence antibody binding.", "mechanism": "Anti-NF155 antibodies may be detected in GBS differential diagnosis.", "protein": "Neurofascin 155", "protein_enriched": { "function": "", "gene_name": "PHTF1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UMS5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12321972" }, { "confidence": "high", "disease": "Docetaxel-resistant prostate cancer", "glycan_involvement": "P-gp is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "P-gp overexpression mediates drug efflux and resistance to docetaxel; triterpene glycosides act independently of P-gp.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12322260" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "ERK1/2 are glycoproteins; glycosylation may affect stability and signaling.", "mechanism": "ERK1/2 overactivation promotes tumor growth, invasion, and drug resistance; inhibited by cucumarioside C1.", "protein": "ERK1/2 (MAPK3/MAPK1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12322260" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "p38 is a glycoprotein; glycosylation may modulate activity.", "mechanism": "p38 MAPK overactivation is linked to drug resistance; inhibited by cucumarioside C1.", "protein": "p38 MAPK (MAPK14)", "protein_enriched": { "function": "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular", "gene_name": "MAPK14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16539" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "IKK\u03b2 is a glycoprotein; glycosylation may affect function.", "mechanism": "IKK\u03b2 mediates NF-\u03baB pathway, promoting cell survival, EMT, and drug resistance.", "protein": "IKK\u03b2 (IKBKB)", "protein_enriched": { "function": "Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other ", "gene_name": "IKBKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14920" }, "relationship_type": "causal", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Cancer cell necroptosis", "glycan_involvement": "MLKL is a glycoprotein; glycosylation may regulate necroptosis.", "mechanism": "Activation of MLKL by cucumarioside C1 suggests induction of necroptosis in cancer cells.", "protein": "MLKL", "relationship_type": "protective", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Cancer cell apoptosis", "glycan_involvement": "CDK11 is a glycoprotein; glycosylation may influence kinase activity.", "mechanism": "Activation promotes apoptosis and cell cycle arrest in cancer cells.", "protein": "PITSLRE (CDK11)", "protein_enriched": { "function": "Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell", "gene_name": "CDK11B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21127" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12322260" }, { "confidence": "high", "disease": "Cancer drug resistance", "glycan_involvement": "N-glycosylation required for P-gp function.", "mechanism": "P-gp mediates multidrug resistance by exporting chemotherapeutics.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "COT is a glycoprotein; glycosylation may affect signaling.", "mechanism": "COT kinase modulates inflammatory signaling and may affect tumor microenvironment.", "protein": "COT (MAP3K8)", "protein_enriched": { "function": "Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) duri", "gene_name": "MAP3K8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41279" }, "relationship_type": "causal", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Cancer cell apoptosis", "glycan_involvement": "PINK1 is a glycoprotein; glycosylation may affect mitochondrial targeting.", "mechanism": "Activation of PINK1 suggests involvement in mitophagy and apoptosis.", "protein": "PINK1", "relationship_type": "protective", "source_pmcid": "PMC12322260" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "GCN2 is a glycoprotein; glycosylation may modulate kinase activity.", "mechanism": "GCN2 activation affects cellular metabolism and stress response.", "protein": "GCN2 (EIF2AK4)", "protein_enriched": { "function": "Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:2532", "gene_name": "EIF2AK4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9P2K8" }, "relationship_type": "causal", "source_pmcid": "PMC12322260" }, { "confidence": "high", "disease": "Gallstones", "glycan_involvement": "AGP glycosylation patterns modulate inflammatory and metabolic pathways relevant to gallstone formation.", "mechanism": "Elevated AGP is associated with increased gallstone risk, possibly via chronic inflammation and metabolic dysregulation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12322271" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Elevated \u03b13-sialylation of AGP correlates with obesity.", "mechanism": "Genetic studies show AGP levels are causally linked to obesity, especially in women.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12322271" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Altered AGP glycosylation (\u03b13-sialylation) linked to metabolic dysfunction.", "mechanism": "Specific AGP glycoforms (e.g., \u03b13-sialylation) are associated with insulin resistance.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12322271" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation patterns (e.g., sialyl-Lewis X) modulate immune response.", "mechanism": "AGP is an acute phase protein elevated in chronic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12322271" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Therapeutic modulation of AGP glycoforms (e.g., sialylation, fucosylation) proposed.", "mechanism": "Targeting AGP glycosylation may modulate gallstone risk.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12322271" }, { "confidence": "high", "disease": "Gallstones", "glycan_involvement": "Glycosylation influences AGP's inflammatory and metabolic effects.", "mechanism": "AGP increases gallstone risk, partially mediated (14.76%) by serum uric acid.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal (partially mediated)", "source_pmcid": "PMC12322271" }, { "confidence": "high", "disease": "Gallstones", "glycan_involvement": "Not specified for subgroups.", "mechanism": "High serum AGP is a risk marker for gallstones, especially in non-Hispanic whites, low-income, and smokers.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12322271" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Sialylation and fucosylation (Lewis antigens) affect selectin binding and inflammation.", "mechanism": "AGP glycoforms (e.g., sialyl-Lewis X, \u03b13-sialylation) modulate immune and metabolic pathways, influencing gallstone formation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal (glycoform-specific)", "source_pmcid": "PMC12322271" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation (Neu5Ac moieties) on acute phase proteins", "mechanism": "Elevated GlycA NMR signal in plasma correlates with increased inflammation in CVD.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation (GlcNAc moieties) on acute phase proteins", "mechanism": "GlycB signal is increased in diabetes, reflecting systemic inflammation.", "protein": "GlycB", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Disease-specific changes in glycosylation pattern", "mechanism": "GlycA is elevated in RA, indicating chronic inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "N-glycosylation changes on acute phase proteins", "mechanism": "Acute phase response increases GlycA signal in COVID-19 patients.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation on acute phase proteins", "mechanism": "GlycA is elevated in sepsis, reflecting acute systemic inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation; glycan pattern may change in disease", "mechanism": "Increased concentration during inflammation; major contributor to GlycA signal.", "protein": "\u03b1-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "N-glycosylation", "mechanism": "Haptoglobin increases during acute infection, contributing to GlycA/GlycB signals.", "protein": "haptoglobin", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "medium", "disease": "Inflammation (general)", "glycan_involvement": "N-glycosylation", "mechanism": "Transferrin decreases during inflammation; inverse contributor to GlycA/GlycB signals.", "protein": "transferrin", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Lipoprotein glycosylation may affect SPC signals", "mechanism": "Increased SPC 3/SPC 2 ratio correlates with higher atherosclerotic risk.", "protein": "SPC 3 / SPC 2 ratio (ApoB100/ApoA1 surrogate)", "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation", "mechanism": "CRP is elevated in CVD, reflecting inflammation; correlates with GlycA/GlycB.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12322961" }, { "confidence": "high", "disease": "Polycystic ovarian syndrome (PCOS)", "glycan_involvement": "ZAG is a glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "ZAG levels are reduced in PCOS, reflecting metabolic dysfunction and adiposity.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation required for ZAG's stability and activity as an adipokine.", "mechanism": "Lower ZAG levels are associated with increased infertility in PCOS, mediating part of obesity's effect on fertility.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects ZAG's secretion and lipid mobilizing function.", "mechanism": "Reduced ZAG correlates with higher BMI and waist circumference; ZAG promotes lipolysis.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation is necessary for ZAG's endocrine activity.", "mechanism": "Low ZAG is linked to increased HOMA-IR; ZAG enhances insulin sensitivity.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12327221" }, { "confidence": "medium", "disease": "Infertility", "glycan_involvement": "Therapeutic modulation may depend on glycosylation for efficacy.", "mechanism": "Restoring ZAG levels may improve fertility odds in PCOS by improving metabolic and hormonal parameters.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12327221" }, { "confidence": "medium", "disease": "Polycystic ovarian syndrome (PCOS)", "glycan_involvement": "Glycosylation supports ZAG's protective adipokine function.", "mechanism": "Higher ZAG levels are associated with improved metabolic and reproductive outcomes in PCOS.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "AMH is a glycoprotein; glycosylation is required for its bioactivity.", "mechanism": "AMH is a gold-standard biomarker for fertility potential in PCOS.", "protein": "Anti-M\u00fcllerian hormone", "protein_enriched": { "function": "Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation", "gene_name": "afsQ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04943" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Polycystic ovarian syndrome (PCOS)", "glycan_involvement": "Glycosylation critical for ZAG's serum stability and detection.", "mechanism": "ZAG discriminates between fertile and infertile PCOS cases with high specificity.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "diagnostic/prognostic biomarker", "source_pmcid": "PMC12327221" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation enables ZAG's adipokine signaling.", "mechanism": "ZAG mediates 13.5% of obesity's inverse effect on fertility in PCOS.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "mediator", "source_pmcid": "PMC12327221" }, { "confidence": "medium", "disease": "Polycystic ovarian syndrome (PCOS)", "glycan_involvement": "Therapeutic modulation may depend on glycosylation for ZAG's function.", "mechanism": "ZAG levels increase with metformin therapy, indicating potential as a marker of therapeutic response.", "protein": "Zinc-\u03b12-glycoprotein", "relationship_type": "therapeutic/prognostic", "source_pmcid": "PMC12327221" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Promotes B cell survival, proliferation, and autoantibody production; serum levels correlate with disease activity and renal involvement.", "protein": "BAFF (B cell-activating factor)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects stability and receptor interactions.", "mechanism": "Elevated serum levels associated with disease activity and cardiovascular involvement.", "protein": "APRIL", "relationship_type": "biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Serum levels correlate with SLE disease activity.", "protein": "BCMA", "protein_enriched": { "function": "Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane (PubMed:36264797). Catalyzes insertion of proteins with alpha-helical transmembrane regions, s", "gene_name": "MTCH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZJ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Sialic acid-binding domain is glycosylated, affecting ligand recognition.", "mechanism": "Absence of SIGLEC1 is a strong negative predictor for SLE diagnosis.", "protein": "SIGLEC1", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation influences receptor binding and immune activation.", "mechanism": "Expressed on Tfh cells; promotes B cell activation and autoantibody production.", "protein": "CD40L", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12328262" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "Produced by Tph cells; correlates with disease activity and renal damage.", "protein": "CXCL13", "relationship_type": "biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation essential for complement activation.", "mechanism": "Low serum levels reflect disease activity; involved in immune complex formation.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Low serum levels indicate active disease; participates in complement cascade.", "protein": "C4", "relationship_type": "biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Retains glycosylation from parent C3; affects immune complex formation.", "mechanism": "Superior to C3 in differentiating SLE from healthy controls.", "protein": "C3dg", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation modulates antigenicity and antibody binding.", "mechanism": "Target of anti-\u03b22GPI antibodies; associated with thrombosis and CNS manifestations in SLE.", "protein": "\u03b22-glycoprotein I (\u03b22GPI)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12328262" }, { "confidence": "high", "disease": "Alcohol-associated/related liver disease (ALD)", "glycan_involvement": "Alcohol impairs N-glycosylation, resulting in transferrin molecules with fewer terminal sialic acids (carbohydrate-deficient).", "mechanism": "Chronic excessive alcohol intake inhibits glycosylation in the Golgi, leading to increased carbohydrate-deficient transferrin (CDT) in serum.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12328905" }, { "confidence": "high", "disease": "Steatotic liver disease (SLD)", "glycan_involvement": "Deficient N-glycosylation of transferrin is detected as increased %CDT.", "mechanism": "CDT levels reflect recent alcohol consumption, aiding in SLD classification based on drinking history.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12328905" }, { "confidence": "high", "disease": "Alcohol dependence", "glycan_involvement": "Alcohol-induced inhibition of glycosylation increases carbohydrate-deficient transferrin.", "mechanism": "Serum %CDT is used to objectively stratify alcohol intake in patients with alcohol dependence.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12328905" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "CRP levels increase during acute influenza infection, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Cell surface glycoproteins mediate immune cell trafficking and activation.", "mechanism": "Altered WBC counts (especially lymphocytes and monocytes) are observed during influenza infection.", "protein": "White blood cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Platelet glycoproteins regulate aggregation and immune interactions.", "mechanism": "Platelet counts decrease during influenza, indicating possible coagulation changes.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Minor glycosylation may affect hemoglobin stability.", "mechanism": "Hemoglobin levels increase in females on day of diagnosis, reflecting acute phase response.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect AST secretion and activity.", "mechanism": "AST increases in influenza, indicating liver involvement.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation modulates albumin half-life and function.", "mechanism": "Albumin decreases in females during influenza, reflecting inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Coagulation disorder", "glycan_involvement": "Glycosylation affects prothrombin activation and clotting.", "mechanism": "PT increases in females during influenza, indicating altered coagulation.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Glycoproteins mediate renal transport and filtration.", "mechanism": "Creatinine decreases and eGFR increases in males during influenza, reflecting kidney function changes.", "protein": "Creatinine transporter glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation regulates glucose transporter function.", "mechanism": "Glucose increases in females during influenza, indicating metabolic stress.", "protein": "Glucose transporter glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Cell surface glycoproteins mediate immune cell interactions.", "mechanism": "Monocyte counts (WBC subset) change during influenza, useful for diagnosis.", "protein": "Monocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12329338" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation regulates receptor trafficking and synaptic localization.", "mechanism": "Memantine inhibits NMDA receptor activity, reducing excitotoxicity; upregulation observed with treatment.", "protein": "GRIN1 (NMDA receptor subunit 1)", "protein_enriched": { "function": "Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed", "gene_name": "GRIN1", "glycan_count": 3, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G31852PQ", "G02815KT" ], "uniprot_id": "Q05586" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12329391" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects receptor function and surface expression.", "mechanism": "Upregulated in response to memantine, possibly as a compensatory mechanism for synaptic plasticity.", "protein": "GRIN2B (NMDA receptor subunit 2B)", "protein_enriched": { "function": "Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed", "gene_name": "GRIN2B", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q13224" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor assembly and function.", "mechanism": "Upregulated in memantine-treated AD hippocampus, indicating synaptic adaptation.", "protein": "GRIA2 (AMPA receptor subunit 2)", "protein_enriched": { "function": "Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), ", "gene_name": "GRIA1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G27391WQ", "G49108TO" ], "uniprot_id": "P42261" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences receptor trafficking.", "mechanism": "Upregulated with memantine, reflecting postsynaptic adaptation.", "protein": "GRIK2 (Kainate receptor subunit 2)", "protein_enriched": { "function": "Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. Binding of the excitatory neurotransmitter ", "gene_name": "GRIK3", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "Q13003" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329391" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for receptor assembly and function.", "mechanism": "Upregulated after memantine, supporting inhibitory signaling and excitatory/inhibitory balance.", "protein": "GABRA1 (GABA-A receptor subunit alpha-1)", "protein_enriched": { "function": "Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:", "gene_name": "GABRA1", "glycan_count": 13, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04414GO", "G07617FP", "G09724ZC", "G22573RC", "G22768VO", "G23799GS", "G40702WU", "G55220VL", "G56014GC", "G68668TB", "G80966KZ", "G91704UR", "G80920RR" ], "uniprot_id": "P14867" }, "relationship_type": "protective", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation essential for receptor surface expression.", "mechanism": "Upregulated with memantine, contributing to inhibitory neurotransmission.", "protein": "GABBR1 (GABA-B receptor subunit 1)", "protein_enriched": { "function": "Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:36103875, PubMed:9872316, PubM", "gene_name": "GABBR1", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9UBS5" }, "relationship_type": "protective", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for matrix assembly and cell interactions.", "mechanism": "Upregulated in AD, reflecting basement membrane thickening due to amyloid deposition.", "protein": "Laminin subunits", "relationship_type": "biomarker", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates cell adhesion and matrix interactions.", "mechanism": "Upregulated in AD, associated with extracellular matrix remodeling.", "protein": "Thrombospondins", "relationship_type": "biomarker", "source_pmcid": "PMC12329391" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for antigen presentation.", "mechanism": "Upregulated in AD hippocampus, indicating activated phagocytes/microglia; normalized by memantine.", "protein": "HLA-DR (MHC class II)", "protein_enriched": { "function": "An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting ", "gene_name": "HLA-DRA", "glycan_count": 88, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G04657PL", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G14972EH", "G27058EU", "G31852PQ", "G32788FZ", "G35541EV", "G37818NZ", "G39471UU", "G41247ZX", "G43223CG", "G43669FQ", "G45395BF", "G47644PP", "G47950XN", "G49642SA", "G50856PC", "G51653BI", "G53075ES", "G54740VA", "G55220VL", "G57776ZS", "G59324HL", "G60834IK", "G62765YT", "G65414LI", "G67164EE", "G68490OW", "G70101JE", "G70232NH", "G75568BH", "G76295SF", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G81637OR", "G86880BF", "G87123QX", "G90382BL", "G92275SC", "G93718GY", "G94156YI", "G95046LV", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G10773YW", "G11101UV", "G14669DU", "G15664MX", "G18647XP", "G22625SJ", "G22768VO", "G23984SE", "G25637MV", "G27947YN", "G28541PG", "G28681TP", "G37399XV", "G39188ZX", "G39446WN", "G40926MX", "G46503DX", "G49018RC", "G57776ZU", "G59626AS", "G59924QI", "G62894KT", "G64527OM", "G70619PT", "G72747WU", "G80920RR", "G82463GQ", "G83460ZZ", "G87661QW", "G89827JR", "G90659AW", "G92050GC", "G95865ZB" ], "uniprot_id": "P01903" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329391" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects transporter stability and localization.", "mechanism": "Upregulated with memantine, enhancing glutamate clearance and reducing excitotoxicity.", "protein": "SLC1A3 (EAAT1, glutamate transporter)", "relationship_type": "protective", "source_pmcid": "PMC12329391" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Regulates UDP-GlcNAc production, affecting global glycosylation and O-GlcNAcylation.", "mechanism": "High PGM3 expression correlates with poor prognosis and higher tumor grade.", "protein": "PGM3", "protein_enriched": { "function": "Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem (PubMed:32325220). The absence of activity may be due to the inabilit", "gene_name": "DPEP3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H4B8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12329428" }, { "confidence": "high", "disease": "Temozolomide-resistant GBM", "glycan_involvement": "Enhances O-GlcNAcylation of proteins, supporting resistance.", "mechanism": "PGM3 upregulation promotes TMZ resistance via increased O-GlcNAcylation.", "protein": "PGM3", "protein_enriched": { "function": "Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem (PubMed:32325220). The absence of activity may be due to the inabilit", "gene_name": "DPEP3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H4B8" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12329428" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Adds O-GlcNAc to serine/threonine residues of proteins.", "mechanism": "OGT-mediated O-GlcNAcylation promotes GBM cell proliferation and survival.", "protein": "OGT", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12329428" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Removes O-GlcNAc from proteins.", "mechanism": "OGA removes O-GlcNAc, balancing modification levels; dysregulation affects tumor biology.", "protein": "OGA", "protein_enriched": { "function": "Cleaves GlcNAc but not GalNAc from O-glycosylated proteins (PubMed:11148210, PubMed:11788610, PubMed:20673219, PubMed:22365600, PubMed:24088714, PubMed:28939839, PubMed:37962578). Deglycosylates a lar", "gene_name": "OGA", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "O60502" }, "relationship_type": "regulatory", "source_pmcid": "PMC12329428" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Indirect; affected by upstream glycosylation pathway modulation.", "mechanism": "GPX4 downregulation by FR054+TMZ induces ferroptosis, enhancing tumor cell death.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC12329428" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Indirect; upregulated via glycosylation pathway inhibition.", "mechanism": "HMOX1 upregulation promotes ferroptosis, increasing sensitivity to TMZ.", "protein": "HMOX1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "HMOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09601" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12329428" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N- and O-glycosylation modulate receptor function.", "mechanism": "Enhanced glycosylation of EGFR supports tumor growth and resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12329428" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Rate-limiting enzymes for UDP-GlcNAc synthesis.", "mechanism": "Upregulation correlates with poor prognosis and increased glycosylation.", "protein": "GFAT1/GFAT2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12329428" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "O-GlcNAcylation at Ser104 regulates KEAP1 function.", "mechanism": "O-GlcNAcylation of KEAP1 affects NRF2 pathway, modulating ferroptosis.", "protein": "KEAP1", "relationship_type": "regulatory", "source_pmcid": "PMC12329428" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Enzymes in UDP-GlcNAc biosynthesis, affecting glycosylation.", "mechanism": "High expression associated with poor survival.", "protein": "GNPNAT1/UAP1", "relationship_type": "biomarker", "source_pmcid": "PMC12329428" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation affects cell surface localization and function.", "mechanism": "Regulates migration, adhesion, and signaling; high expression correlates with poor prognosis; target of daratumumab therapy.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Heparan sulfate glycosaminoglycan chains mediate cell-matrix interactions.", "mechanism": "Cell adhesion molecule; abnormal expression linked to proliferation, invasion, and drug resistance.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Extracellular immunoglobulin-like domains are glycosylated, affecting receptor interactions.", "mechanism": "Regulates immune cell signaling; double-positive expression with CD200 predicts poor prognosis.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329740" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Polysialylation modulates cell adhesion and migration.", "mechanism": "Membrane glycoprotein; expression associated with disease progression.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation modulates receptor binding and immune regulation.", "mechanism": "Immunosuppressive molecule; double-positive with CD45 predicts poor prognosis via immune evasion.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "biomarker", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation of both proteins influences immune cell interactions and tumor microenvironment.", "mechanism": "Double-positive expression is an independent predictor of poor overall and progression-free survival; reflects immune evasion.", "protein": "CD45 & CD200 (co-expression)", "relationship_type": "biomarker", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may affect antibody binding and efficacy.", "mechanism": "Targeted by daratumumab; therapy exploits high CD38 expression on MM cells.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12329740" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Heparan sulfate chains facilitate growth factor binding.", "mechanism": "Promotes tumor cell proliferation and invasion.", "protein": "CD138 (Syndecan-1)", "relationship_type": "causal", "source_pmcid": "PMC12329740" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation affects ligand-receptor interaction.", "mechanism": "Potential immune checkpoint target; mediates immunosuppression via CD200R.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12329740" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation modulates TCR/BCR signaling.", "mechanism": "Associated with immune evasion and cancer progression.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "causal", "source_pmcid": "PMC12329740" }, { "confidence": "high", "disease": "Hematologic malignancies", "glycan_involvement": "Glycosylation stabilizes haptocorrin and affects its serum half-life.", "mechanism": "Increased haptocorrin release in myeloproliferative syndromes leads to elevated serum B12.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Renal failure", "glycan_involvement": "Glycosylation is essential for transcobalamin II secretion and function.", "mechanism": "Excess transcobalamin II in renal failure increases circulating B12.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Solid neoplasia", "glycan_involvement": "Altered glycosylation may affect haptocorrin clearance in cancer.", "mechanism": "Tumor cells and liver metastases increase haptocorrin release, raising serum B12.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "N-glycosylation required for hepatic secretion of transcobalamin II.", "mechanism": "Decreased hepatic synthesis of transcobalamin II impairs B12 tissue uptake, increasing serum B12.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation patterns of AFP change in cancer, affecting detection.", "mechanism": "Elevated alpha-fetoprotein is a marker of liver cancer; often co-occurs with high B12.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Solid neoplasia", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP \u00d7 B12 index (BCI) >40,000 predicts short-term mortality in advanced cancer.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation modulates haptocorrin hepatic clearance.", "mechanism": "Liver dysfunction increases haptocorrin release, elevating serum B12.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation may affect haptocorrin's immunological interactions.", "mechanism": "Paradoxical elevation of B12 due to increased haptocorrin in inflammation.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "medium", "disease": "Solid neoplasia", "glycan_involvement": "N-glycosylation impacts transcobalamin II stability in cancer.", "mechanism": "Altered transcobalamin II levels in cancer affect B12 distribution.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation changes in AFP reflect liver pathology.", "mechanism": "AFP is elevated in cirrhosis and liver regeneration, often with high B12.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331276" }, { "confidence": "high", "disease": "CADASIL", "glycan_involvement": "NOTCH3 is a heavily glycosylated receptor; glycosylation modulates ligand binding and receptor function.", "mechanism": "Mutations (especially cysteine-altering) in NOTCH3 disrupt Notch signaling, causing small vessel disease and leukoencephalopathy.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12331493" }, { "confidence": "high", "disease": "Vascular Parkinsonism (VaP)", "glycan_involvement": "Glycosylation affects NOTCH3 receptor trafficking and signaling in vascular smooth muscle cells.", "mechanism": "NOTCH3 variants (including cysteine-sparing) are associated with VaP, possibly via vascular dysfunction and WMLs.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "risk factor/causal", "source_pmcid": "PMC12331493" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "LRRK2 is glycosylated; glycosylation may affect kinase activity and neuronal localization.", "mechanism": "LRRK2 mutations increase susceptibility to PD and parkinsonism.", "protein": "LRRK2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "PLA2G6 is a secreted glycoprotein; glycosylation may affect secretion and enzymatic function.", "mechanism": "Heterozygous PLA2G6 variants increase risk for familial and sporadic parkinsonism.", "protein": "PLA2G6", "protein_enriched": { "function": "Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of ", "gene_name": "PLA2G6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60733" }, "relationship_type": "risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "PSP-like syndrome/atypical parkinsonism", "glycan_involvement": "TGM6 is glycosylated; glycosylation may regulate enzyme stability.", "mechanism": "TGM6 mutations cause late-onset atypical parkinsonism (e.g., PSP-like syndromes).", "protein": "TGM6", "protein_enriched": { "function": "G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-st", "gene_name": "GRM4", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q14833" }, "relationship_type": "causal", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "CD36 is a glycoprotein; glycosylation is critical for membrane localization and ligand binding.", "mechanism": "CD36 variants are associated with PD risk and cerebral ischemia.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "Vascular Parkinsonism (VaP)", "glycan_involvement": "UBR4 is glycosylated; glycosylation may affect protein-protein interactions in ECM.", "mechanism": "UBR4 variants linked to adult-onset ataxia, WMLs, brain atrophy, and parkinsonism; involved in vascular matrix production.", "protein": "UBR4", "protein_enriched": { "function": "E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:3818292", "gene_name": "UBR4", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G58356JX", "G80920RR" ], "uniprot_id": "Q5T4S7" }, "relationship_type": "risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "high", "disease": "Stroke/White Matter Lesions", "glycan_involvement": "Collagen glycosylation is essential for ECM assembly and vessel integrity.", "mechanism": "COL4A1 mutations predispose to arterial wall weakness, stroke, and WMLs.", "protein": "COL4A1", "relationship_type": "causal/risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "Vascular Parkinsonism (VaP)", "glycan_involvement": "Collagen glycosylation affects vessel wall structure and function.", "mechanism": "COL22A1 mutations impair vessel integrity, increasing risk for cerebral hemorrhage and VaP.", "protein": "COL22A1", "protein_enriched": { "function": "Acts as a cell adhesion ligand for skin epithelial cells and fibroblasts", "gene_name": "COL22A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "Q8NFW1" }, "relationship_type": "causal/risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "TNR is a highly glycosylated ECM protein; glycosylation modulates cell adhesion and signaling.", "mechanism": "TNR variants found in familial PD cases; ECM protein involved in neuronal signaling.", "protein": "TNR", "protein_enriched": { "function": "Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. These interactions can influence cellular behavior by either evoking a stable adhesion an", "gene_name": "TNR", "glycan_count": 2, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "Q92752" }, "relationship_type": "risk factor", "source_pmcid": "PMC12331493" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "APP is N-glycosylated, affecting trafficking and processing.", "mechanism": "APP mutations increase A\u03b2 production and deposition in vessel walls, driving CAA pathology.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "BACE1 is N-glycosylated, influencing stability and activity.", "mechanism": "Elevated BACE1 expression in endothelial cells and neurons increases amyloidogenic APP cleavage, promoting A\u03b2 accumulation.", "protein": "BACE1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "ADAM10 is N-glycosylated, modulating its function.", "mechanism": "ADAM10 mediates non-amyloidogenic APP cleavage; reduced ADAM10 (via microRNAs) shifts balance toward A\u03b2 production.", "protein": "ADAM10", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "LRP1 is heavily N-glycosylated, essential for ligand binding and endocytosis.", "mechanism": "Reduced LRP1 expression in VSMCs impairs A\u03b2 clearance, accelerating CAA progression.", "protein": "LRP1", "relationship_type": "causal", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "Neprilysin is N-glycosylated, affecting enzymatic activity.", "mechanism": "Decreased neprilysin in VSMCs reduces A\u03b2 degradation, increasing vascular deposition.", "protein": "Neprilysin", "relationship_type": "causal", "source_pmcid": "PMC12331648" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "Claudin-5 is O-glycosylated, influencing tight junction stability.", "mechanism": "Reduced claudin-5 in CAA-affected capillaries indicates BBB leakage and endothelial dysfunction.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331648" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "Occludin is O-glycosylated, modulating junctional integrity.", "mechanism": "Loss of occludin correlates with BBB breakdown in CAA.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "CAA", "glycan_involvement": "GFAP is glycosylated, affecting filament assembly.", "mechanism": "Elevated GFAP in CSF/serum reflects astrocyte activation and early CAA pathology.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331648" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "VEGFR2 is N-glycosylated, required for receptor function.", "mechanism": "Decreased VEGFR2 in microvessels with CAA impairs angiogenesis and vascular repair.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331648" }, { "confidence": "medium", "disease": "CAA", "glycan_involvement": "CD44 is heavily glycosylated, mediating cell-matrix interactions.", "mechanism": "Upregulated CD44 in neurons links to ECM remodeling and pro-fibrotic changes in CAA.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12331648" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "AMA-M2 is an autoantibody glycoprotein; glycosylation may affect antigen recognition.", "mechanism": "AMA-M2 is a serological marker for PBC, indicating immune-mediated bile duct injury.", "protein": "Antimitochondrial M2 antibody (AMA-M2)", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ANA is an autoantibody glycoprotein; glycosylation may modulate immune complex formation.", "mechanism": "ANA positivity is a diagnostic marker for AIH, reflecting loss of tolerance to nuclear antigens.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ASMA is an autoantibody glycoprotein; glycosylation may influence antigen binding.", "mechanism": "ASMA is a diagnostic marker for AIH, targeting actin filaments in hepatocytes.", "protein": "Antismooth muscle antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "IgG glycosylation can affect effector functions and immune activation.", "mechanism": "F-actin IgG is a specific marker for AIH, indicating immune response against cytoskeletal proteins.", "protein": "F-actin-specific IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "IgG glycosylation modulates antibody effector functions and inflammation.", "mechanism": "Elevated serum IgG is characteristic of AIH, reflecting chronic immune activation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated ALP is a marker of cholestatic injury in PBC.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "GGT is a glycoprotein; glycosylation influences enzymatic activity.", "mechanism": "Elevated GGT reflects bile duct injury and cholestasis in PBC.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "PBC-AIH overlap syndrome", "glycan_involvement": "Autoantibody glycosylation may affect immune response and disease severity.", "mechanism": "AMA-M2 positivity supports diagnosis of overlap syndrome with PBC features.", "protein": "Antimitochondrial M2 antibody (AMA-M2)", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "PBC-AIH overlap syndrome", "glycan_involvement": "IgG glycosylation may modulate inflammatory response in overlap syndrome.", "mechanism": "Elevated IgG supports AIH component in overlap syndrome.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "PBC-AIH overlap syndrome", "glycan_involvement": "Autoantibody glycosylation may influence immune complex formation and tissue injury.", "mechanism": "ANA positivity supports AIH component in overlap syndrome.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12332042" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "CREG2 is a secreted glycoprotein; glycosylation likely affects secretion and immune modulation.", "mechanism": "High CREG2 expression is associated with improved prognosis, regulates angiogenesis and immune responses via VEGF and TGF-\u03b2 pathways.", "protein": "CREG2", "protein_enriched": { "function": "Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcripti", "gene_name": "EHMT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31166QV", "G62765YT", "G84712KL", "G89373FA", "G49108TO" ], "uniprot_id": "Q9H9B1" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC12332372" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "CDCP1 is a transmembrane glycoprotein; glycosylation may affect cell adhesion and signaling.", "mechanism": "Low CDCP1 expression correlates with poor prognosis; CDCP1 suppresses metastasis via Wnt/\u03b2-catenin signaling and EMT inhibition.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC12332372" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "ANLN overexpression promotes tumor proliferation via PI3K/Akt activation and mitotic dysregulation.", "protein": "ANLN", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "RHOF upregulation drives cytoskeletal remodeling and EMT, contributing to tumor progression.", "protein": "RHOF", "protein_enriched": { "function": "Binds to and activates protein kinase PAK1 (PubMed:11459829). Plays a role in the regulation of cell morphology, cytoskeletal organization and focal adhesion assembly during cell migration (PubMed:114", "gene_name": "RHOU", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q7L0Q8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Immunotherapy resistance in LUAD", "glycan_involvement": "Glycosylation may modulate immune recognition and cytokine interactions.", "mechanism": "High CREG2 expression is associated with increased immune cell infiltration and improved anti-PD-L1 response.", "protein": "CREG2", "protein_enriched": { "function": "Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcripti", "gene_name": "EHMT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31166QV", "G62765YT", "G84712KL", "G89373FA", "G49108TO" ], "uniprot_id": "Q9H9B1" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Metastatic lung cancer", "glycan_involvement": "Glycosylation may regulate CDCP1 stability and cell surface localization.", "mechanism": "CDCP1 inhibits metastasis; loss of CDCP1 promotes aggressive phenotypes via Wnt pathway inactivation.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation affects secretion and immune function.", "mechanism": "CREG2 downregulation impairs antitumor immunity and promotes hypoxia-driven progression.", "protein": "CREG2", "protein_enriched": { "function": "Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcripti", "gene_name": "EHMT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31166QV", "G62765YT", "G84712KL", "G89373FA", "G49108TO" ], "uniprot_id": "Q9H9B1" }, "relationship_type": "causal", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Immunotherapy resistance in LUAD", "glycan_involvement": "Glycosylation may modulate receptor interactions.", "mechanism": "CDCP1 upregulation impairs calcium-dependent T-cell activation, contributing to immunosuppressive microenvironment.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "causal", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may affect therapeutic efficacy.", "mechanism": "CREG2 modulates angiogenesis and immune response, suggesting potential as a therapeutic target.", "protein": "CREG2", "protein_enriched": { "function": "Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcripti", "gene_name": "EHMT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31166QV", "G62765YT", "G84712KL", "G89373FA", "G49108TO" ], "uniprot_id": "Q9H9B1" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12332372" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may influence drug sensitivity.", "mechanism": "CDCP1 expression levels predict response to chemotherapy and immunotherapy.", "protein": "CDCP1", "protein_enriched": { "function": "May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a ", "gene_name": "CDCP1", "glycan_count": 40, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G06356OH", "G27058EU", "G59626AS", "G84452RH", "G70101JE", "G15169WU", "G39446WN", "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G45395BF", "G90659AW", "G04657PL", "G05049YU", "G14972EH", "G23719VF", "G41071NU", "G42124LM", "G70619PT", "G80920RR", "G95177YH", "G00912UN", "G08918WF", "G10486CT", "G20210JR", "G23294PN", "G44215PV", "G82463GQ", "G92050GC", "G25079LO", "G46503DX", "G48584BU", "G72747WU", "G92406TI", "G49108TO" ], "uniprot_id": "Q9H5V8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332372" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Deletions in glycosylated regions may alter antigenicity and immune recognition.", "mechanism": "GP3 hypervariable region deletions (3-aa at 243-248) in ZJ01 strain associated with increased pathogenicity and immune evasion.", "protein": "GP3", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Deletions may affect glycosylation sites, impacting viral entry and immune escape.", "mechanism": "GP4 hypervariable region deletions (4-aa at 63-68) in ZJ01 strain linked to altered virulence and host cell tropism.", "protein": "GP4", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "GP5 glycosylation influences antigenicity and vaccine efficacy.", "mechanism": "ORF5 gene encoding GP5 used for phylogenetic classification and strain identification.", "protein": "GP5", "relationship_type": "biomarker", "source_pmcid": "PMC12332522" }, { "confidence": "high", "disease": "Acute respiratory disease in piglets", "glycan_involvement": "Altered glycosylation may modulate immune response and tissue tropism.", "mechanism": "GP3 deletions in ZJ01 strain contribute to lung pathology and fever.", "protein": "GP3", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Reproductive failure in sows", "glycan_involvement": "Glycosylation changes may affect placental crossing and fetal infection.", "mechanism": "GP4 deletions implicated in reproductive disorders via immune modulation.", "protein": "GP4", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Septicemia in swine", "glycan_involvement": "Glycan modifications may facilitate systemic dissemination.", "mechanism": "GP3 variation linked to systemic viral spread and high viremia.", "protein": "GP3", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Not directly glycosylated; used as a serological marker.", "mechanism": "N protein used for diagnostic detection via immunofluorescence and antibody assays.", "protein": "N protein", "protein_enriched": { "function": "Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-meth", "gene_name": "PB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03427" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycosylation site variability affects vaccine efficacy.", "mechanism": "GP3 hypervariable region is a target for vaccine design due to its role in immune escape.", "protein": "GP3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycan modifications influence antigenicity.", "mechanism": "GP4 region is considered for vaccine and therapeutic development.", "protein": "GP4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332522" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "N-glycosylation of GP5 modulates immune recognition.", "mechanism": "GP5 is essential for viral infectivity and immune response modulation.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC12332522" }, { "confidence": "high", "disease": "Tricuspid regurgitation syndrome", "glycan_involvement": "NT-Pro-BNP is glycosylated, which affects its stability and secretion.", "mechanism": "Elevated NT-Pro-BNP reflects cardiac stress and severity of TR; higher levels correlate with advanced TR stages and worse prognosis.", "protein": "NT-Pro-BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Tricuspid regurgitation syndrome", "glycan_involvement": "Albumin glycosylation status may affect its half-life and function.", "mechanism": "Lower serum albumin levels indicate hepatic dysfunction and systemic involvement in advanced TR.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Tricuspid regurgitation syndrome", "glycan_involvement": "Hemoglobin glycosylation (glycated hemoglobin) can reflect metabolic status.", "mechanism": "Reduced hemoglobin reflects anemia secondary to chronic disease and systemic involvement in TR.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Tricuspid regurgitation syndrome", "glycan_involvement": "Platelet glycoprotein glycosylation affects platelet function and clearance.", "mechanism": "Lower platelet count is associated with advanced TR and hepatic dysfunction.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects NT-Pro-BNP stability and detection.", "mechanism": "NT-Pro-BNP is a standard marker for heart failure severity and prognosis.", "protein": "NT-Pro-BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Altered glycosylation may occur in liver disease.", "mechanism": "Low albumin is a marker of hepatic synthetic dysfunction in TR patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Renal failure", "glycan_involvement": "Glycosylation may affect renal clearance.", "mechanism": "NT-Pro-BNP levels are elevated in renal failure due to reduced clearance.", "protein": "NT-Pro-BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Edema", "glycan_involvement": "Glycosylation may affect albumin's oncotic pressure properties.", "mechanism": "Hypoalbuminemia contributes to edema formation in advanced TR.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Tricuspid regurgitation syndrome", "glycan_involvement": "Glycosylation status may influence NT-Pro-BNP response to therapy.", "mechanism": "Reduction in NT-Pro-BNP after TTVR indicates therapeutic efficacy.", "protein": "NT-Pro-BNP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332669" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Altered glycosylation may affect platelet lifespan in liver disease.", "mechanism": "Thrombocytopenia reflects portal hypertension and liver dysfunction in TR.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12332669" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation required for VEGFR cell surface expression and ligand binding.", "mechanism": "VEGFR-mediated angiogenesis promotes tumor growth; inhibition by TKIs (donafenib, lenvatinib) suppresses neovascularization.", "protein": "VEGFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332680" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation modulates PDGFR folding and function.", "mechanism": "PDGFR signaling supports tumor stroma and angiogenesis; blockade by TKIs impairs tumor microenvironment.", "protein": "PDGFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332680" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and regulates its immune inhibitory function.", "mechanism": "TACE-induced hypoxia upregulates PD-L1, potentially increasing immune evasion; PD-L1 is targetable by ICIs.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12332680" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation status may affect VEGFR signaling and drug sensitivity.", "mechanism": "VEGFR inhibition by TKIs leads to reduced nitric oxide signaling, causing hypertension.", "protein": "VEGFR", "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12332680" }, { "confidence": "low", "disease": "Drug-induced hepatitis", "glycan_involvement": "Glycosylation of PD-L1 influences its stability and immune interactions.", "mechanism": "Upregulation of PD-L1 post-TACE may exacerbate immune-mediated liver injury.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12332680" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "N-glycosylation affects PSA stability and detection sensitivity.", "mechanism": "Elevated serum PSA indicates presence and progression of prostate cancer.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12332727" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "Glycosylation modulates PSMA cell surface localization and antibody recognition.", "mechanism": "PSMA expression is upregulated in prostate cancer cells and used for PET imaging and targeted therapy.", "protein": "PSMA", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Skip metastasis to mediastinal/hilar lymph nodes", "glycan_involvement": "Glycosylation required for VEGF-C secretion and receptor binding.", "mechanism": "VEGF-C promotes lymphangiogenesis, enabling tumor cells to bypass regional nodes.", "protein": "VEGF-C", "relationship_type": "causal", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Skip metastasis to mediastinal/hilar lymph nodes", "glycan_involvement": "Glycosylation influences VEGF-A stability and activity.", "mechanism": "VEGF-A increases lymphatic permeability, facilitating distant lymph node colonization.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Bone metastasis", "glycan_involvement": "Glycosylation regulates integrin conformation and ligand binding.", "mechanism": "Integrin \u03b1V\u03b23 mediates vascular adhesion and hematogenous dissemination to bone.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Metastatic prostate cancer", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune checkpoint inhibitor efficacy.", "mechanism": "PD-L1 expression modulates immune evasion in metastatic prostate cancer.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Bone metastasis", "glycan_involvement": "Glycosylation impacts CXCL12 secretion and receptor interaction.", "mechanism": "CXCL12 attracts circulating tumor cells to bone microenvironment.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "causal", "source_pmcid": "PMC12332727" }, { "confidence": "medium", "disease": "Bone metastasis", "glycan_involvement": "Glycosylation required for TGF-\u03b2 maturation and activity.", "mechanism": "TGF-\u03b2 reactivates dormant metastatic cells in bone.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12332727" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "AAT is a glycoprotein; glycosylation is required for its stability and secretion.", "mechanism": "Mutations in the SERPINA1 gene encoding AAT reduce its ability to inhibit neutrophil elastase, leading to increased lung tissue damage and inflammation.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "Glycosylation affects AAT folding and secretion; deficiency may be exacerbated by glycan defects.", "mechanism": "AAT deficiency due to genetic mutations leads to unchecked protease activity, causing progressive lung tissue destruction.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12333050" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation status may influence AAT serum levels and function.", "mechanism": "AAT mutations (M/S, M/Z, M/I, S/S genotypes) are enriched in difficult-to-treat asthma patients.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Asthma exacerbations", "glycan_involvement": "Glycosylation required for proper AAT function; mutations may affect glycan processing.", "mechanism": "PiS and PiZ variants of SERPINA1 gene increase risk of asthma exacerbations, ER visits, and hospitalizations.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Asthma (difficult-to-treat)", "glycan_involvement": "Glycosylation is essential for AAT secretion and anti-inflammatory activity.", "mechanism": "12.5% of Colombian adults with difficult-to-treat asthma have AAT mutations, suggesting a role in disease severity.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12333050" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Therapeutic AAT preparations require correct glycosylation for efficacy.", "mechanism": "AAT replacement therapy may be considered in patients with deficiency and severe asthma.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation impacts AAT stability and anti-protease activity.", "mechanism": "AATD genotypes (including M/S) are frequent in COPD patients, indicating risk for disease development.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation is required for AAT's anti-inflammatory and anti-protease functions.", "mechanism": "Normal AAT glycoprotein protects lung tissue from neutrophil elastase-mediated damage.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "protective", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Mutations may affect glycosylation, impacting secretion and function.", "mechanism": "SERPINA1 mutations (especially Pi*Z) are associated with increased asthma severity and poor control.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12333050" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation status may be relevant for diagnostic assays and therapeutic monitoring.", "mechanism": "AAT genotype screening can identify patients at risk for severe asthma and guide management.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12333050" }, { "confidence": "high", "disease": "Hepatobiliary disease", "glycan_involvement": "N-glycosylation affects stability and secretion.", "mechanism": "Elevated ALP indicates biliary pressure and hepatocyte injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Paracetamol-induced hepatotoxicity", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "ALT leakage into serum reflects hepatocyte membrane damage.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Paracetamol-induced hepatotoxicity", "glycan_involvement": "N-glycosylation influences stability.", "mechanism": "Elevated AST is a marker of hepatocyte injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "Increased GGT reflects biliary tract injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation affects half-life and function.", "mechanism": "Reduced serum albumin is a hallmark of chronic liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Hepatobiliary disease", "glycan_involvement": "Glycosylation modulates cytokine secretion and receptor binding.", "mechanism": "TNF-\u03b1 drives inflammation and hepatocyte apoptosis.", "protein": "Tumor necrosis factor-\u03b1 (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Paracetamol-induced hepatotoxicity", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "IL-1\u03b2 promotes inflammatory cascade and cell death.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects receptor interaction.", "mechanism": "IL-6 contributes to chronic inflammation and fibrogenesis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Paracetamol-induced hepatotoxicity", "glycan_involvement": "N-glycosylation influences enzyme stability.", "mechanism": "HO-1 induction reduces oxidative stress and inflammation.", "protein": "Heme oxygenase-1 (HO-1)", "relationship_type": "protective", "source_pmcid": "PMC12333573" }, { "confidence": "high", "disease": "Hepatobiliary disease", "glycan_involvement": "Not glycosylated; acts via regulation of glycoprotein antioxidants.", "mechanism": "Nrf2 activation upregulates antioxidant genes, protecting hepatocytes.", "protein": "Nuclear factor erythroid 2-related factor 2 (Nrf2)", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "NFE2L2", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16236" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333573" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation affects LRG1 stability and serum detection.", "mechanism": "LRG1 is elevated in inflammatory states and measured as part of antibody panels in CD diagnosis.", "protein": "Leucine-rich alpha-2 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12333731" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation is essential for secretion and stability in feces.", "mechanism": "Used to assess protein-losing enteropathy and intestinal inflammation in CD.", "protein": "Fecal alpha-1 antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC12333731" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation modulates CRP's plasma half-life and immune recognition.", "mechanism": "CRP is an acute phase reactant elevated during active inflammation in CD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333731" }, { "confidence": "low", "disease": "Kidney oxalate calculi", "glycan_involvement": "Glycosylation affects renal clearance.", "mechanism": "LRG1 may be measured in patients with CD who develop renal complications.", "protein": "Leucine-rich alpha-2 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12333731" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Glycosylation required for function and detection.", "mechanism": "Elevated fecal alpha-1 antitrypsin indicates protein loss contributing to malnutrition in CD.", "protein": "Fecal alpha-1 antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC12333731" }, { "confidence": "high", "disease": "Intracranial Atherosclerotic Disease (ICAD)", "glycan_involvement": "Glycosylation critical for receptor function and ligand binding.", "mechanism": "Inhibition of platelet aggregation to improve vessel patency post-thrombectomy.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333737" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation modulates receptor conformation and drug binding.", "mechanism": "Used off-label to prevent re-occlusion after EVT in stroke patients with ICAD.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333737" }, { "confidence": "medium", "disease": "Reperfusion Injury", "glycan_involvement": "Glycosylation affects secretion and activity of MMPs.", "mechanism": "MMPs produced by activated microglia disrupt the blood\u2013brain barrier, exacerbating injury.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333737" }, { "confidence": "medium", "disease": "Hemorrhagic Transformation", "glycan_involvement": "Glycosylation regulates MMP stability and localization.", "mechanism": "MMP-mediated BBB breakdown increases risk of hemorrhagic conversion post-EVT.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333737" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation may influence GFAP release and detection.", "mechanism": "Circulating GFAP levels predict infarct progression and hemorrhagic risk.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333737" }, { "confidence": "high", "disease": "Cancer-associated dermatomyositis (CADM)", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against TIF1-\u03b3 are found in CADM, indicating immune cross-reactivity between tumor and muscle antigens.", "protein": "TIF1-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12333741" }, { "confidence": "high", "disease": "Cancer-associated dermatomyositis (CADM)", "glycan_involvement": "Glycosylation may modulate immune response and autoantigen presentation.", "mechanism": "Autoantibodies against NXP2 are associated with CADM, reflecting paraneoplastic immune response.", "protein": "NXP2", "relationship_type": "biomarker", "source_pmcid": "PMC12333741" }, { "confidence": "medium", "disease": "Gestational trophoblastic neoplasia (GTN)", "glycan_involvement": "PD-L1 glycosylation regulates its stability and immune checkpoint function.", "mechanism": "Altered PD-L1 expression in GTN contributes to immune evasion by trophoblastic cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333741" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Glycosylation may influence autoantibody binding.", "mechanism": "Presence of anti-TIF1-\u03b3 antibodies is linked to DM, especially with underlying malignancy.", "protein": "TIF1-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12333741" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Glycosylation may affect antigen processing and immune response.", "mechanism": "Anti-NXP2 antibodies are associated with DM and cancer risk.", "protein": "NXP2", "relationship_type": "biomarker", "source_pmcid": "PMC12333741" }, { "confidence": "medium", "disease": "Dermatomyositis (DM)", "glycan_involvement": "PD-L1 glycosylation modulates immune signaling.", "mechanism": "Immune checkpoint dysregulation may contribute to autoimmunity in DM.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12333741" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "YKL-40 is a secreted glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Elevated CSF YKL-40 reflects astrocyte activation and neuroinflammation in AD; higher in AD and APOE \u03b54 carriers.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation affects secretion and function.", "mechanism": "Elevated CSF sTREM2 reflects microglial activation and neuroinflammation in AD; increases in MCI and AD.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Klotho is a glycoprotein; glycosylation is required for stability and function.", "mechanism": "KL-VS heterozygosity (higher klotho levels) is associated with lower AD risk, less tau pathology, and reduced neuroinflammation.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated CSF Ng indicates synaptic damage in AD; lower in fit KL-VS HET individuals.", "protein": "Neurogranin (Ng)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau can be O-glycosylated, which may affect aggregation.", "mechanism": "CSF pTau181 is a marker of tau pathology and neurodegeneration in AD; lower in fit KL-VS HET individuals.", "protein": "Phosphorylated tau 181 (pTau181)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau can be O-glycosylated.", "mechanism": "CSF tTau reflects neurodegeneration; lower in fit KL-VS HET individuals.", "protein": "Total tau (tTau)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "YKL-40 is an early indicator of astrocyte-mediated neuroinflammation.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation affects secretion.", "mechanism": "sTREM2 reflects microglial activation and neuroinflammatory response.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Neurodegeneration", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Higher klotho levels (KL-VS HET) protect against neurodegeneration and synaptic dysfunction.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12333875" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated YKL-40 is associated with synaptic dysfunction in AD.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12333875" }, { "confidence": "high", "disease": "Blastic plasmacytoid dendritic cell neoplasm (BPDCN)", "glycan_involvement": "CD123 is a glycoprotein; glycosylation may affect receptor stability and ligand binding.", "mechanism": "CD123 is highly expressed on BPDCN cells and is targeted by tagraxofusp for selective cytotoxicity.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Capillary leak syndrome (CLS)", "glycan_involvement": "Glycosylation of CD123 may influence immune recognition and drug binding.", "mechanism": "Tagraxofusp targeting CD123 can induce CLS as an adverse event, possibly via endothelial damage.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "causal (drug-induced)", "source_pmcid": "PMC12333968" }, { "confidence": "high", "disease": "Capillary leak syndrome (CLS)", "glycan_involvement": "Albumin is a glycoprotein; glycosylation affects its stability and half-life.", "mechanism": "Supplemental albumin is used to prevent and manage CLS during tagraxofusp therapy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective/therapeutic", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Tumor lysis syndrome (TLS)", "glycan_involvement": "Glycosylation may affect CD123 expression and drug efficacy.", "mechanism": "Tagraxofusp-induced rapid tumor cell death via CD123 targeting can trigger TLS.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "causal (drug-induced)", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Central nervous system involvement in BPDCN", "glycan_involvement": "Glycosylation may affect CD123 localization and function.", "mechanism": "CD123 expression in CNS-involved BPDCN may be targeted by tagraxofusp, though CNS penetration is uncertain.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12333968" }, { "confidence": "high", "disease": "Relapsed/refractory BPDCN", "glycan_involvement": "Glycosylation may modulate receptor expression and drug binding.", "mechanism": "CD123 remains expressed in relapsed/refractory BPDCN, allowing tagraxofusp efficacy.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333968" }, { "confidence": "high", "disease": "Blastic plasmacytoid dendritic cell neoplasm (BPDCN)", "glycan_involvement": "Glycosylation affects albumin's serum stability.", "mechanism": "Serum albumin levels are used to assess eligibility and monitor safety during tagraxofusp treatment.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker (supportive care)", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "Glycosylation may affect CD123 targeting.", "mechanism": "CD123 is expressed in AML and is being explored as a target for tagraxofusp and other agents.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "therapeutic_target (investigational)", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Acute lymphoblastic leukemia (ALL)", "glycan_involvement": "Glycosylation may affect receptor function.", "mechanism": "CD123 is expressed in ALL and may be targeted by novel therapies.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "therapeutic_target (investigational)", "source_pmcid": "PMC12333968" }, { "confidence": "low", "disease": "Non-Hodgkin lymphoma", "glycan_involvement": "Glycosylation may modulate receptor activity.", "mechanism": "CD123 is expressed in some non-Hodgkin lymphomas and may be a therapeutic target.", "protein": "CD123 (IL-3 receptor alpha chain)", "relationship_type": "therapeutic_target (investigational)", "source_pmcid": "PMC12333968" }, { "confidence": "medium", "disease": "Xanthogranulomatous pyelonephritis (XGP)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated ALP reflects renal parenchymal damage and inflammation.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "medium", "disease": "Xanthogranulomatous pyelonephritis (XGP)", "glycan_involvement": "GGT is glycosylated; glycan moieties modulate its activity.", "mechanism": "Elevated GGT indicates renal and biliary tract involvement.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "medium", "disease": "Xanthogranulomatous pyelonephritis (XGP)", "glycan_involvement": "Glycosylation mediates cell-cell interactions and immune response.", "mechanism": "Foamy histiocytes (macrophages) accumulate in XGP, expressing surface glycoproteins involved in inflammation.", "protein": "Foamy histiocyte surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12334269" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Bacterial glycoproteins interact with host glycan receptors.", "mechanism": "Bacterial glycoproteins mediate adhesion and immune evasion in UTI.", "protein": "Coagulase-negative staphylococcal protein (Staphylococcus hemolyticus surface proteins)", "relationship_type": "causal", "source_pmcid": "PMC12334269" }, { "confidence": "medium", "disease": "Xanthogranulomatous pyelonephritis (XGP)", "glycan_involvement": "Loss of glycoprotein-mediated tissue integrity.", "mechanism": "Destruction and replacement of renal parenchymal glycoproteins by inflammatory cells in XGP.", "protein": "Renal parenchymal glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12334269" }, { "confidence": "low", "disease": "Malakoplakia", "glycan_involvement": "Glycosylation patterns may distinguish disease states.", "mechanism": "Similar macrophage glycoprotein expression in malakoplakia and XGP.", "protein": "Foamy histiocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "low", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Glycosylation affects ALP isoform distribution.", "mechanism": "ALP may be elevated in RCC, mimicking XGP.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "low", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Glycosylation modulates GGT activity.", "mechanism": "GGT elevation may occur in RCC and XGP.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "low", "disease": "Tuberculosis (renal)", "glycan_involvement": "Glycosylation influences immune cell recruitment.", "mechanism": "Granulomatous inflammation with macrophage glycoprotein expression in renal TB.", "protein": "Foamy histiocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12334269" }, { "confidence": "medium", "disease": "Xanthogranulomatous pyelonephritis (XGP)", "glycan_involvement": "Bacterial glycoproteins interact with host immune system.", "mechanism": "Bacterial infection triggers XGP; glycoproteins mediate host-pathogen interaction.", "protein": "Coagulase-negative staphylococcal protein (Staphylococcus hemolyticus surface proteins)", "relationship_type": "causal", "source_pmcid": "PMC12334269" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I affects its antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are diagnostic for APS; their presence is required for laboratory diagnosis.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12334272" }, { "confidence": "medium", "disease": "Intracardiac thrombosis", "glycan_involvement": "Glycosylation modulates \u03b22-glycoprotein I structure and immune recognition.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies promote thrombosis by interfering with coagulation and endothelial function.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12334272" }, { "confidence": "medium", "disease": "Pulmonary thromboembolism", "glycan_involvement": "Altered glycosylation may influence immune complex formation.", "mechanism": "Antibody-mediated activation of \u03b22-glycoprotein I leads to hypercoagulability and embolic events.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12334272" }, { "confidence": "medium", "disease": "Valvular heart disease", "glycan_involvement": "Glycosylation affects deposition and immune response.", "mechanism": "Immune complexes involving \u03b22-glycoprotein I deposit on valves, causing thickening and vegetations.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12334272" }, { "confidence": "high", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "vWF is a highly glycosylated plasma protein; glycosylation affects its stability and function.", "mechanism": "Elevated vWF indicates endothelial dysfunction and is associated with PSVD severity.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "ADAMTS13 is glycosylated, which is important for secretion and activity.", "mechanism": "Reduced ADAMTS13 activity reflects endothelial damage and is inversely related to PSVD progression.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "P-selectin is a glycoprotein; glycosylation mediates its cell adhesion properties.", "mechanism": "Elevated sP-selectin reflects increased platelet activation and aggregation in PSVD.", "protein": "Soluble P-selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "medium", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "GPVI is glycosylated; glycosylation affects receptor function.", "mechanism": "Increased sGPVI indicates enhanced platelet activation and aggregation in PSVD.", "protein": "Soluble Glycoprotein VI", "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "FVIII is heavily glycosylated, which is essential for its stability and activity.", "mechanism": "Elevated FVIII is associated with hypercoagulability and vascular lesions in PSVD.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation modulates vWF multimerization and function.", "mechanism": "vWF levels are further increased in PSVD with portal hypertension, reflecting advanced endothelial dysfunction.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "medium", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "Zonulin is a glycoprotein-like molecule; glycosylation may affect its secretion.", "mechanism": "Elevated zonulin reflects increased intestinal permeability, contributing to endotoxemia and PSVD pathogenesis.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Porto-sinusoidal vascular disorder (PSVD)", "glycan_involvement": "TLR4 is N-glycosylated, which is critical for LPS recognition and signaling.", "mechanism": "Increased TLR4+ macrophages in liver bind LPS, triggering inflammation and vascular injury in PSVD.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12334859" }, { "confidence": "medium", "disease": "Sinusoidal capillarisation", "glycan_involvement": "CD34 is a sialomucin glycoprotein; glycosylation is essential for its function.", "mechanism": "Increased CD34+ staining marks sinusoidal capillarisation, a microvascular change in PSVD.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "medium", "disease": "Obliterative portal venopathy", "glycan_involvement": "CD42b is a glycoprotein; glycosylation is important for platelet adhesion.", "mechanism": "Increased CD42b+ platelets in sinusoids indicate platelet aggregation, contributing to vascular occlusion in PSVD.", "protein": "CD42b", "relationship_type": "biomarker", "source_pmcid": "PMC12334859" }, { "confidence": "high", "disease": "Lysosomal Acid Lipase Deficiency (LAL-D)", "glycan_involvement": "LAL is a glycoprotein; glycosylation is required for lysosomal targeting and function.", "mechanism": "Pathogenic variants in LIPA gene cause loss of LAL activity, leading to lysosomal accumulation of triglycerides and cholesteryl esters.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Lysosomal Acid Lipase Deficiency (LAL-D)", "glycan_involvement": "Glycosylation of sebelipase alfa is essential for lysosomal delivery and therapeutic efficacy.", "mechanism": "Recombinant glycoprotein enzyme replacement restores LAL activity, reducing substrate accumulation and improving liver outcomes.", "protein": "Sebelipase alfa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Lysosomal Acid Lipase Deficiency (LAL-D)", "glycan_involvement": "ALT is a glycoprotein; glycosylation affects stability and serum half-life.", "mechanism": "Elevated ALT indicates liver injury due to substrate accumulation in LAL-D.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Lysosomal Acid Lipase Deficiency (LAL-D)", "glycan_involvement": "AST is a glycoprotein; glycosylation influences secretion and activity.", "mechanism": "Elevated AST reflects hepatocellular damage in LAL-D.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Defective glycoprotein function due to LIPA mutations impairs lysosomal lipid metabolism.", "mechanism": "Chronic LAL deficiency leads to progressive liver damage, fibrosis, and cirrhosis.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Premature atherosclerosis", "glycan_involvement": "Glycosylation required for LAL function in lipid metabolism.", "mechanism": "LAL deficiency causes abnormal lipid profiles, promoting early atherosclerosis.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12334869" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Therapeutic glycoprotein's glycosylation enables lysosomal targeting.", "mechanism": "Enzyme replacement reduces liver injury and may prevent progression to fibrosis/cirrhosis.", "protein": "Sebelipase alfa", "relationship_type": "protective", "source_pmcid": "PMC12334869" }, { "confidence": "medium", "disease": "Premature atherosclerosis", "glycan_involvement": "Glycosylation critical for enzyme function.", "mechanism": "Restores lipid metabolism, potentially reducing cardiovascular risk.", "protein": "Sebelipase alfa", "relationship_type": "protective", "source_pmcid": "PMC12334869" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Impaired glycoprotein function leads to persistent liver damage.", "mechanism": "Chronic liver injury and fibrosis from LAL deficiency may predispose to hepatocellular carcinoma.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation affects ALT's serum stability as a biomarker.", "mechanism": "ALT elevation is an indicator of ongoing liver injury and risk of fibrosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334869" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "SORT1 is a glycoprotein; glycosylation may affect its trafficking and function, but specific glycan roles not detailed.", "mechanism": "SORT1 is overexpressed in NSCLC tissues; its downregulation inhibits proliferation, migration, invasion, and promotes apoptosis in NSCLC cells.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 is overexpressed in breast cancer tissues and associated with tumor progression.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 is upregulated in ovarian cancer, implicated in tumorigenesis.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Thyroid Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 is overexpressed in thyroid cancer tissues.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Liver Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "Elevated SORT1 correlates with poor prognosis in liver cancer.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "High SORT1 expression is associated with poor outcomes in glioblastoma.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "low", "disease": "Colorectal Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 implicated in colorectal cancer pathogenesis.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "low", "disease": "Gastric Cancer", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 implicated in gastric cancer pathogenesis.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334890" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "miR-146a regulates SORT1, impacting atherosclerosis development.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "causal", "source_pmcid": "PMC12334890" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "General glycoprotein function; no specific glycan modification described.", "mechanism": "SORT1 involved in Alzheimer's disease pathogenesis.", "protein": "Sortilin-1 (SORT1)", "relationship_type": "causal", "source_pmcid": "PMC12334890" }, { "confidence": "medium", "disease": "Cholangitis-Cholangiohepatitis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP levels increase with inflammation in cholangitis-cholangiohepatitis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "medium", "disease": "Cholangitis-Cholangiohepatitis", "glycan_involvement": "ILs are glycoproteins; glycosylation modulates receptor binding.", "mechanism": "ILs mediate inflammatory response in biliary tract.", "protein": "Interleukin (IL)", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "medium", "disease": "Cholangitis-Cholangiohepatitis", "glycan_involvement": "Platelet surface glycoproteins mediate activation and aggregation.", "mechanism": "Platelet count and activation (PLR, MPV/PLT) reflect inflammation severity.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "low", "disease": "Hepatic Fibrosis", "glycan_involvement": "Erythropoietin glycosylation is essential for activity.", "mechanism": "Altered erythropoiesis and increased RDW indicate fibrosis.", "protein": "Erythropoietin", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "low", "disease": "Chronic Hepatitis", "glycan_involvement": "Albumin glycosylation affects half-life and function.", "mechanism": "Serum albumin decreases in chronic liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Platelet glycoproteins regulate activation.", "mechanism": "MPV increases with platelet activation in sepsis.", "protein": "Mean Platelet Volume (MPV)", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "high", "disease": "Hepatic Fibrosis", "glycan_involvement": "Erythrocyte membrane glycoproteins affect RDW.", "mechanism": "Elevated RDW is an early marker of hepatic fibrosis and cirrhosis.", "protein": "Red Cell Distribution Width (RDW)", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "high", "disease": "Cholangitis-Cholangiohepatitis", "glycan_involvement": "Neutrophil surface glycoproteins mediate migration.", "mechanism": "Neutrophilia reflects active inflammation; NLR is elevated.", "protein": "Neutrophil", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "high", "disease": "Cholangitis-Cholangiohepatitis", "glycan_involvement": "Lymphocyte glycoproteins regulate immune response.", "mechanism": "Lymphopenia occurs due to apoptosis and redistribution; NLR and RDW/LYM are elevated.", "protein": "Lymphocyte", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "medium", "disease": "Chronic Hepatitis", "glycan_involvement": "Monocyte glycoproteins mediate inflammation.", "mechanism": "MLR correlates with disease severity.", "protein": "Monocyte", "relationship_type": "biomarker", "source_pmcid": "PMC12335203" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "sGP is heavily glycosylated, which affects immune evasion and detection.", "mechanism": "sGP is secreted during Ebola infection and detected in plasma as a marker of active infection.", "protein": "Ebola virus soluble glycoprotein (sGP)", "protein_enriched": { "function": "Trimeric GP1,2 complexes form the virion surface spikes and mediate the viral entry processes, with GP1 acting as the receptor-binding subunit and GP2 as the membrane fusion subunit. At later times of", "gene_name": "GP", "glycan_count": 0, "glycosylation_sites_count": 17, "glytoucan_ids": [], "uniprot_id": "Q05320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "GP is highly glycosylated (N- and O-glycans), modulating host immune response.", "mechanism": "GP is present on the viral surface and is targeted by immunosensors for diagnosis.", "protein": "Ebola virus glycoprotein (GP)", "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is extensively N-glycosylated, affecting antigenicity and immune recognition.", "mechanism": "Spike protein is the main antigen for serological detection and neutralizing antibody response.", "protein": "SARS-CoV-2 spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Nucleocapsid protein is abundant in infected cells and used for diagnostic detection.", "protein": "SARS-CoV-2 nucleocapsid protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "Middle East respiratory syndrome (MERS)", "glycan_involvement": "Spike is N-glycosylated, influencing immune evasion and detection.", "mechanism": "Spike protein is used as a diagnostic marker in immunosensors.", "protein": "MERS-CoV spike protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 23, "glytoucan_ids": [], "uniprot_id": "K9N5Q8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "E-protein is glycosylated, affecting viral entry and immune recognition.", "mechanism": "E-protein is the main antigen for serological diagnosis and immune response.", "protein": "Dengue virus envelope protein (E-protein)", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P29990" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "Glycosylation modulates antigenicity and host interactions.", "mechanism": "Envelope protein is targeted by antibodies for diagnostic detection.", "protein": "Zika virus envelope protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the host cell membrane and packages the viral RNA into a nucleocapsid that forms the core of the mature virus particle. During virus entry, may induce genom", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q32ZE1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "medium", "disease": "Hepatitis E", "glycan_involvement": "Capsid protein is glycosylated, influencing immune recognition.", "mechanism": "Capsid protein is detected by immunosensors for diagnosis.", "protein": "Hepatitis E virus capsid protein", "protein_enriched": { "function": "Methyltransferase: Displays a capping enzyme activity. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enz", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6J8G2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation affects host-pathogen interaction and immune evasion.", "mechanism": "HopQ is an outer membrane glycoprotein used as a diagnostic marker.", "protein": "HopQ", "protein_enriched": { "function": "A 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures, may also play a role in translation. Binds GTP and analogs. Binds the 70S ribosome", "gene_name": "bipA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZLZ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "CagA is glycosylated, which may affect its immunogenicity.", "mechanism": "CagA is a virulence factor detected by aptasensors for H. pylori diagnosis.", "protein": "CagA", "protein_enriched": { "function": "May be necessary for the transcription, folding, export, or function of the cytotoxin", "gene_name": "cagA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55980" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335303" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "IgM is a heavily N-glycosylated glycoprotein; glycosylation is essential for its structure and function.", "mechanism": "Low serum IgM (<0.67 g/L) is a strong early diagnostic marker distinguishing MM from other causes of Ig elevation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "N-glycosylation affects IgG stability and effector function.", "mechanism": "Monoclonal IgG elevation is the most common MM subtype; IgG levels reflect tumor burden and prognosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "IgA is N- and O-glycosylated, influencing its polymerization and immune function.", "mechanism": "Monoclonal IgA elevation is the second most common MM subtype; IgA levels are used for diagnosis and monitoring.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Light chains are glycosylated, affecting solubility and aggregation.", "mechanism": "Elevated serum free light chains indicate clonal plasma cell proliferation; used in MM diagnosis and prognosis.", "protein": "Serum free light chains (S-\u03ba, S-\u03bb)", "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Glycosylation impacts renal handling and aggregation.", "mechanism": "High urinary light chains (Bence Jones protein) are diagnostic for MM and associated with renal damage.", "protein": "Urine free light chains (U-\u03ba, U-\u03bb)", "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "N-glycosylation is essential for \u03b22MG stability.", "mechanism": "Elevated \u03b22MG correlates with tumor burden and renal dysfunction in MM; prognostic marker.", "protein": "Beta-2 Microglobulin (\u03b22MG)", "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "medium", "disease": "Connective Tissue Diseases (CTD)", "glycan_involvement": "Altered IgG glycosylation patterns are associated with autoimmune activity.", "mechanism": "Polyclonal IgG elevation reflects immune dysregulation in CTD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "medium", "disease": "Connective Tissue Diseases (CTD)", "glycan_involvement": "Glycosylation modulates IgA immune complex formation.", "mechanism": "Polyclonal IgA elevation is seen in CTD, reflecting immune activation.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Waldenstr\u00f6m\u2019s Macroglobulinemia (WM)", "glycan_involvement": "IgM glycosylation is critical for pentameric structure.", "mechanism": "Monoclonal IgM elevation is characteristic of WM.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "medium", "disease": "Monoclonal Gammopathy of Undetermined Significance (MGUS)", "glycan_involvement": "Glycosylation status may influence progression risk.", "mechanism": "Monoclonal IgG elevation is a hallmark of MGUS, a precursor to MM.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335419" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "CRP is a glycoprotein; its glycosylation is essential for stability and function.", "mechanism": "CRP levels rise in response to inflammation caused by S. aureus infection; elevated levels predict increased mortality.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "high", "disease": "Pneumonia (S. aureus-associated)", "glycan_involvement": "Glycosylation maintains CRP solubility and bioactivity.", "mechanism": "High CRP levels are associated with increased mortality in S. aureus pneumonia.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "medium", "disease": "Endocarditis (S. aureus-associated)", "glycan_involvement": "Glycosylation affects CRP's interaction with immune cells.", "mechanism": "CRP is elevated in endocarditis; higher levels indicate severe infection and poor prognosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "medium", "disease": "Osteomyelitis", "glycan_involvement": "Glycosylation required for CRP secretion and function.", "mechanism": "CRP is used to monitor inflammation and response to therapy in bone infections.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "medium", "disease": "Septic arthritis", "glycan_involvement": "Glycosylation supports CRP's immune recognition.", "mechanism": "CRP levels correlate with severity and prognosis in joint infections.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "medium", "disease": "Prosthetic joint infection", "glycan_involvement": "Glycosylation ensures CRP stability in circulation.", "mechanism": "CRP is elevated in prosthetic infections; used for diagnosis and monitoring.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "medium", "disease": "Skin and soft tissue infection", "glycan_involvement": "Glycosylation required for CRP's inflammatory response.", "mechanism": "CRP increases with severity of skin/soft tissue infections.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects CRP's half-life and immune interactions.", "mechanism": "CRP is a marker of systemic inflammation and sepsis severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Glycosylation is essential for CRP's function as an acute-phase reactant.", "mechanism": "CRP levels are elevated in bacteremia; higher levels predict poor outcome.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12335657" }, { "confidence": "low", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Glycosylation may affect CRP's interaction with complement and immune cells.", "mechanism": "CRP may modulate immune response; targeting CRP could influence inflammation in S. aureus infection.", "protein": "C-reactive protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335657" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma (THCA)", "glycan_involvement": "SPP1 is an N-linked glycoprotein; glycosylation may affect secretion and immune interactions.", "mechanism": "SPP1 is overexpressed in papillary THCA, correlates with tumor stage, proximity to capsule, and immune cell infiltration.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (THCA)", "glycan_involvement": "Glycosylation may modulate SPP1's interaction with immune cells.", "mechanism": "SPP1 involvement in immune pathways and cell activation suggests potential for immunomodulatory therapy.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (THCA)", "glycan_involvement": "N-glycosylation may regulate SPP1's extracellular matrix interactions.", "mechanism": "SPP1 overexpression promotes tumor progression, migration, and invasion via immune and EMT-related pathways.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "causal", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (THCA)", "glycan_involvement": "Glycosylation may influence SPP1's immunomodulatory functions.", "mechanism": "SPP1 expression correlates with inflammatory marker NPR, indicating enhanced immune inflammatory response.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "N-linked glycosylation may affect SPP1's stability and immune interactions.", "mechanism": "SPP1 overexpression correlates with immune cell infiltration and poor survival.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "N-glycosylation may regulate SPP1's function in tumor microenvironment.", "mechanism": "SPP1 is associated with cancer-related signaling pathways and poor prognosis.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect SPP1's role in cell adhesion and migration.", "mechanism": "SPP1 is overexpressed and involved in cancer progression.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "N-glycosylation may influence SPP1's extracellular functions.", "mechanism": "High SPP1 expression predicts poor prognosis.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "low", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "Glycosylation may modulate SPP1's signaling activity.", "mechanism": "SPP1 co-expressed genes enriched in AML-related pathways.", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "pathway involvement", "source_pmcid": "PMC12335683" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma (THCA)", "glycan_involvement": "N-glycosylation may impact SPP1's detectability and function.", "mechanism": "SPP1 expression distinguishes malignant from normal thyroid tissue (AUC ~0.67\u20130.76).", "protein": "Secreted phosphoprotein 1 (SPP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335683" }, { "confidence": "high", "disease": "Vitamin B12 Deficiency", "glycan_involvement": "Glycosylation is essential for intrinsic factor stability and function.", "mechanism": "Intrinsic factor is required for Vitamin B12 absorption; deficiency or dysfunction leads to B12 deficiency.", "protein": "Intrinsic Factor", "relationship_type": "causal", "source_pmcid": "PMC12335742" }, { "confidence": "high", "disease": "Pernicious Anemia", "glycan_involvement": "Autoantibodies may target glycosylated epitopes on intrinsic factor.", "mechanism": "Autoimmune destruction of intrinsic factor or parietal cells impairs B12 absorption, causing pernicious anemia.", "protein": "Intrinsic Factor", "relationship_type": "causal", "source_pmcid": "PMC12335742" }, { "confidence": "medium", "disease": "Megaloblastic Anemia", "glycan_involvement": "Glycosylation affects transferrin's serum half-life and iron-binding.", "mechanism": "Transferrin saturation and iron levels are measured to differentiate anemia types.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335742" }, { "confidence": "medium", "disease": "Megaloblastic Anemia", "glycan_involvement": "Glycosylation modulates ferritin secretion and stability.", "mechanism": "Ferritin levels help exclude iron deficiency in megaloblastic anemia.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335742" }, { "confidence": "medium", "disease": "Megaloblastic Anemia", "glycan_involvement": "Serum LDH is glycosylated, affecting its clearance.", "mechanism": "Elevated LDH indicates increased cell turnover and hemolysis in megaloblastic anemia.", "protein": "Lactate Dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12335742" }, { "confidence": "medium", "disease": "Pernicious Anemia", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "Autoimmune IgG targets intrinsic factor or parietal cells, leading to B12 malabsorption.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12335742" }, { "confidence": "low", "disease": "Autoimmune Pancytopenia", "glycan_involvement": "ANA glycosylation affects antigenicity and detection.", "mechanism": "ANA is used to rule out autoimmune causes of pancytopenia.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12335742" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation of gp210 may affect antigenicity and autoantibody recognition.", "mechanism": "Anti-gp210 autoantibodies are highly specific for PBC diagnosis, especially in AMA-negative patients.", "protein": "gp210", "protein_enriched": { "function": "Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and t", "gene_name": "JUP", "glycan_count": 12, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G43089EG", "G52527GH", "G75983OB", "G13694XX", "G22310AV", "G56784JY", "G57888GL", "G06356OH", "G11629QQ", "G84452RH" ], "uniprot_id": "P14923" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Anti-sp100 autoantibodies are common in PBC and support diagnosis, especially in AMA-negative cases.", "protein": "sp100", "protein_enriched": { "function": "Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation a", "gene_name": "SP100", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P23497" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Potential glycosylation influences antigenicity.", "mechanism": "Anti-sp140 autoantibodies are associated with PBC and help in diagnosis.", "protein": "sp140", "protein_enriched": { "function": "Component of the nuclear body, also known as nuclear domain 10, PML oncogenic domain, and KR body (PubMed:8910577). May be involved in the pathogenesis of acute promyelocytic leukemia and viral infect", "gene_name": "SP140", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated ALP is a diagnostic and prognostic marker for PBC and treatment response.", "protein": "ALP (Alkaline Phosphatase)", "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation of mitochondrial antigens may influence autoantibody binding.", "mechanism": "AMA M2 autoantibodies target mitochondrial glycoprotein antigens, highly specific for PBC.", "protein": "AMA M2", "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "FGF-19 is glycosylated, which may affect receptor binding and therapeutic efficacy.", "mechanism": "FGF-19 modulators (e.g., aldafermin) improve cholestasis in PBC.", "protein": "FGF-19", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335757" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "Albumin glycosylation status may change in liver disease.", "mechanism": "Serum albumin levels reflect liver synthetic function and cirrhosis severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "GGT is glycosylated; glycan changes may affect activity.", "mechanism": "Elevated GGT is associated with cholestasis and PBC.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "low", "disease": "Liver Cirrhosis", "glycan_involvement": "AST glycosylation may affect serum levels.", "mechanism": "Elevated AST is a marker of hepatocellular injury and cirrhosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "low", "disease": "Liver Cirrhosis", "glycan_involvement": "ALT glycosylation may influence stability.", "mechanism": "Elevated ALT is a marker of liver injury and cirrhosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335757" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is glycosylated, which may affect antibody binding and immune recognition.", "mechanism": "AQP4-IgG autoantibodies target AQP4 on astrocytes, causing demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "high", "disease": "Varicella-Zoster Virus-induced Transverse Myelitis (VZV-TM)", "glycan_involvement": "VZV envelope glycoproteins are heavily glycosylated, facilitating host cell attachment and immune evasion.", "mechanism": "VZV glycoproteins mediate viral entry and neuroinvasion, triggering spinal cord inflammation.", "protein": "Varicella-Zoster Virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12335943" }, { "confidence": "medium", "disease": "Varicella-Zoster Virus-induced Transverse Myelitis (VZV-TM)", "glycan_involvement": "IgG Fc glycosylation modulates immune effector functions.", "mechanism": "VZV-specific IgG in CSF/serum indicates recent or ongoing infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Beta-2-glycoprotein I is N-glycosylated, influencing antigenicity and antibody binding.", "mechanism": "Elevated beta-2-glycoprotein I antibodies are diagnostic for antiphospholipid syndrome.", "protein": "Beta-2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Autoantibodies are glycoproteins; glycosylation affects immune complex formation.", "mechanism": "Presence of lupus anticoagulant is associated with SLE and increased thrombotic risk.", "protein": "Lupus anticoagulant (antiphospholipid antibodies)", "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Antibody glycosylation modulates pathogenicity and clearance.", "mechanism": "Anti-dsDNA antibodies are specific for SLE and correlate with disease activity.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Antibody glycosylation may affect immune response and tissue targeting.", "mechanism": "Anti-Ro antibodies are associated with SLE and Sj\u00f6gren\u2019s syndrome.", "protein": "Anti-Ro (SSA) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "medium", "disease": "Varicella-Zoster Virus-induced Transverse Myelitis (VZV-TM)", "glycan_involvement": "AQP4 glycosylation may modulate susceptibility to antibody-mediated damage.", "mechanism": "VZV infection may trigger anti-AQP4 antibody production, leading to NMOSD-like LETM.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal (rare)", "source_pmcid": "PMC12335943" }, { "confidence": "low", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "VZV glycoprotein glycosylation aids immune evasion, possibly influencing autoimmunity.", "mechanism": "VZV infection may precipitate NMOSD in predisposed individuals.", "protein": "Varicella-Zoster Virus glycoproteins", "relationship_type": "trigger", "source_pmcid": "PMC12335943" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "IgG glycosylation patterns are altered in SLE, affecting inflammation.", "mechanism": "Elevated IgG autoantibodies (e.g., anti-dsDNA, anti-Ro) are diagnostic for SLE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335943" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG induce myelin sheath and oligodendrocyte destruction, leading to CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Anti-NMDAR encephalitis", "glycan_involvement": "Glycosylation of MOG may influence immune recognition and cross-reactivity.", "mechanism": "MOG antibodies are frequently detected in patients with anti-NMDAR encephalitis, indicating disease overlap.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation status may modulate MOG immunogenicity.", "mechanism": "MOG antibodies are present in a subset of MS patients, associated with demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorders (NMOSD)", "glycan_involvement": "Glycosylation may affect MOG antibody binding.", "mechanism": "MOG antibodies are less frequent in NMOSD but may indicate overlapping pathology.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "NMDAR is glycosylated; glycosylation affects receptor trafficking and function.", "mechanism": "Functional NMDARs on oligodendrocytes are activated under pathological conditions; MOGAD may co-exist with anti-NMDAR encephalitis.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12336174" }, { "confidence": "high", "disease": "Anti-NMDAR encephalitis", "glycan_involvement": "Glycosylation modulates NMDAR surface expression and immunogenicity.", "mechanism": "Autoantibodies against NMDAR cause encephalitis; overlap with MOGAD observed.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "Glycosylation sites may be targeted to modulate immune response.", "mechanism": "Targeting MOG antibodies may prevent demyelination and improve outcomes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336174" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "Seropositivity for MOG antibodies is diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336174" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "Glycosylation affects NMDAR function and susceptibility to Hcy-induced toxicity.", "mechanism": "Hcy acts as an excitatory agonist of NMDAR, promoting excitotoxicity and oligodendrocyte injury in MOGAD.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12336174" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "Glycosylation may influence antibody binding and disease severity.", "mechanism": "MOG antibody levels predict poor recovery and relapse in first-attack MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336174" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation affects lactoferrin stability and immune function.", "mechanism": "Elevated plasma lactoferrin reflects neutrophil activation and systemic inflammation in T2D.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336180" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "Glycosylation modulates lactoferrin's antimicrobial and anti-inflammatory properties in tears.", "mechanism": "Lactoferrin levels are altered in DED, reflecting ocular surface inflammation and tear film dysfunction.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", 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"glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", 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"G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336180" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation affects lactoferrin's release and function during inflammation.", "mechanism": "Plasma lactoferrin to neutrophil ratio (LFNR) is elevated in T2D-DED, indicating systemic inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336180" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation status may affect albumin's stability and function.", "mechanism": "Lower albumin levels indicate insulin deficiency and inflammation in T2D.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336180" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation is required for CRP's stability and immune activity.", "mechanism": "Elevated CRP reflects systemic inflammation in T2D and DED.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336180" }, { "confidence": "medium", "disease": "Dry Eye Disease", "glycan_involvement": "Glycosylation enhances lactoferrin's antimicrobial activity in tears.", "mechanism": "Lactoferrin stabilizes tear film and protects ocular surface from infection.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12336180" }, { "confidence": "medium", "disease": "Meniere\u2019s disease", "glycan_involvement": "Hydrophilic glycan moieties facilitate water retention and volume increase.", "mechanism": "Excess glycoprotein secretion by ELS attracts water, contributing to endolymphatic hydrops and vertigo attacks.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12336207" }, { "confidence": "medium", "disease": "Endolymphatic hydrops", "glycan_involvement": "Glycosylation increases hydrophilicity and water-binding capacity.", "mechanism": "Glycoprotein secretion increases endolymph volume, leading to hydrops.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Viral labyrinthitis", "glycan_involvement": "Glycosylation may modulate immune recognition and clearance.", "mechanism": "ELS glycoprotein production and immune activity help remove viral debris from inner ear.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12336207" }, { "confidence": "medium", "disease": "Meniere\u2019s disease", "glycan_involvement": "Chronic glycoprotein deposition may promote fibrotic glycan structures.", "mechanism": "Repeated drainage and glycoprotein accumulation lead to ELS fibrosis and loss of function.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Endolymphatic sac tumor", "glycan_involvement": "Altered glycosylation patterns may serve as tumor markers.", "mechanism": "Abnormal glycoprotein expression may indicate ELS neoplastic transformation.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Meniere\u2019s disease", "glycan_involvement": "Inhibiting glycosylation could decrease hydrophilicity and fluid retention.", "mechanism": "Targeting glycoprotein secretion or glycan modification may reduce endolymph volume.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Meniere\u2019s disease", "glycan_involvement": "Molecular mimicry involving glycan epitopes may drive autoimmunity.", "mechanism": "Auto-antibodies against ELS glycoproteins may trigger immune-mediated damage.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Meniere\u2019s disease", "glycan_involvement": "Glycosylation may enhance binding and clearance of pathogens.", "mechanism": "ELS glycoproteins facilitate removal of noxious agents, defending hair cells.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Endolymphatic hydrops", "glycan_involvement": "Accumulated glycoproteins with persistent glycan structures exacerbate fluid imbalance.", "mechanism": "Impaired glycoprotein clearance leads to persistent hydrops and hair cell loss.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12336207" }, { "confidence": "low", "disease": "Meniere\u2019s disease", "glycan_involvement": "Glycosylation state may reflect ELS functional status.", "mechanism": "Levels of ELS glycoprotein may correlate with disease activity and progression.", "protein": "Endolymphatic sac glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12336207" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Leptin is glycosylated, which affects its stability and secretion.", "mechanism": "Leptin levels are significantly elevated in obese PCOS patients and correlate with BMI and visceral adiposity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Glycosylation modulates leptin's bioactivity and receptor interaction.", "mechanism": "Leptin is associated with metabolic risk and disease severity in PCOS, especially in obese patients.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Adiponectin glycosylation is essential for multimerization and function.", "mechanism": "Adiponectin levels are reduced in obese PCOS patients; higher levels are protective against metabolic dysfunction.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation affects adiponectin's insulin-sensitizing activity.", "mechanism": "Low adiponectin is associated with increased insulin resistance in PCOS.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12336424" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Resistin is glycosylated, influencing its secretion and inflammatory activity.", "mechanism": "Elevated resistin correlates with increased insulin resistance and obesity in PCOS.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC12336424" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects its stability and receptor binding.", "mechanism": "TNF-\u03b1 is elevated in obese PCOS, contributing to systemic inflammation and metabolic dysfunction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "IL-6 glycosylation modulates its secretion and activity.", "mechanism": "IL-6 is increased in obese PCOS, promoting inflammation and insulin resistance.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation influences leptin's metabolic signaling.", "mechanism": "Leptin levels predict metabolic syndrome components in PCOS.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "medium", "disease": "Hyperandrogenism", "glycan_involvement": "SHBG glycosylation affects its binding affinity and serum half-life.", "mechanism": "Reduced SHBG in obese PCOS is linked to increased free androgens and disease severity.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation is required for adiponectin's anti-inflammatory and metabolic effects.", "mechanism": "Higher adiponectin is associated with reduced risk of metabolic syndrome in PCOS.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12336424" }, { "confidence": "high", "disease": "Microscopic polyangiitis (MPA)", "glycan_involvement": "MPO is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-MPO antibodies (MPO-ANCA) are present in most MPA cases and correlate with disease activity.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "high", "disease": "Livedo racemosa", "glycan_involvement": "Glycosylation of MPO may influence immune recognition.", "mechanism": "MPO-ANCA positivity is associated with livedo racemosa as a cutaneous manifestation of MPA.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "high", "disease": "Granulomatosis with polyangiitis (GPA)", "glycan_involvement": "PR3 is a glycoprotein; glycosylation may modulate antigenicity.", "mechanism": "PR3-ANCA is the predominant biomarker in GPA.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Granulomatosis with polyangiitis (GPA)", "glycan_involvement": "Glycosylation may affect immune response.", "mechanism": "MPO-ANCA is present in a minority of GPA cases.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Eosinophilic granulomatosis with polyangiitis (EGPA)", "glycan_involvement": "Glycosylation may influence antibody binding.", "mechanism": "MPO-ANCA positivity is seen in ~45% of EGPA cases, often with cutaneous involvement.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "low", "disease": "Polyarteritis nodosa (PAN)", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Rarely, MPO-ANCA positivity is seen in cutaneous PAN, especially drug-induced cases.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Beta-2-glycoprotein I is heavily glycosylated, affecting its immunogenicity.", "mechanism": "Anti-beta-2-glycoprotein antibodies are used in thrombophilia testing.", "protein": "Beta-2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation is important for stability and function.", "mechanism": "Deficiency is tested in thrombophilia workup.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Deficiency is tested in thrombophilia workup.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "medium", "disease": "Microscopic polyangiitis (MPA)", "glycan_involvement": "CRP is glycosylated, which may affect its function.", "mechanism": "CRP is used to monitor inflammation in MPA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336637" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "Defective O-mannosylation and subsequent glycan modifications on \u03b1-DG.", "mechanism": "Impaired glycosylation of \u03b1-DG disrupts its binding to extracellular matrix proteins, destabilizing muscle structure.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "Essential for ribitol phosphate addition to \u03b1-DG O-glycans.", "mechanism": "CRPPA mutations impair CDP-ribitol biosynthesis, reducing ribitol phosphate modification of \u03b1-DG, leading to disease.", "protein": "CRPPA", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "Transfers ribitol phosphate to O-mannosylated \u03b1-DG.", "mechanism": "FKTN uses CDP-ribitol to transfer ribitol phosphate to \u03b1-DG; mutations disrupt this process.", "protein": "FKTN", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis", "gene_name": "CTSF", "glycan_count": 21, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G27058EU", "G41071NU", "G45395BF", "G58954YZ", "G62765YT", "G72667IM", "G75983OB", "G80920RR", "G83460ZZ", "G92050GC", "G92275SC", "G02815KT", "G23505EP", "G27126ED", "G28681TP", "G31852PQ", "G39188ZX", "G41247ZX", "G73430PD", "G80510PV" ], "uniprot_id": "Q9UBX1" }, "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "Ribitol phosphate modification of \u03b1-DG O-glycans.", "mechanism": "FKRP transfers ribitol phosphate to \u03b1-DG; mutations cause defective glycosylation.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "O-mannosyl glycan extension on \u03b1-DG.", "mechanism": "POMGNT1 is involved in O-mannosyl glycan extension on \u03b1-DG; mutations lead to hypoglycosylation.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "\u03b1-dystroglycanopathy", "glycan_involvement": "Initiates O-mannosylation on \u03b1-DG.", "mechanism": "POMT1 initiates O-mannosylation of \u03b1-DG; mutations cause defective glycosylation.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "CMD with mental retardation (CMD-MR)", "glycan_involvement": "Reduced ribitol phosphate modification of \u03b1-DG O-glycans.", "mechanism": "Compound heterozygous CRPPA mutations (including novel c.1119+2T>G) impair \u03b1-DG glycosylation, causing CMD-MR.", "protein": "CRPPA", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "Walker-Warburg syndrome (WWS)", "glycan_involvement": "Near-complete loss of functional O-glycans on \u03b1-DG.", "mechanism": "Severe loss of \u03b1-DG glycosylation leads to WWS, the most severe \u03b1-dystroglycanopathy phenotype.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Partial reduction of O-glycan structures on \u03b1-DG.", "mechanism": "Partial loss of \u03b1-DG glycosylation results in milder LGMD phenotype.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "Congenital muscular dystrophy-dystroglycanopathy (CMD)", "glycan_involvement": "Impaired ribitol phosphate addition to \u03b1-DG O-glycans.", "mechanism": "CRPPA mutations cause defective \u03b1-DG glycosylation, leading to CMD.", "protein": "CRPPA", "relationship_type": "causal", "source_pmcid": "PMC12336902" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBsAg is a glycoprotein with N-linked glycosylation important for secretion and immune recognition.", "mechanism": "HBsAg presence in serum indicates active HBV infection and is used to diagnose and monitor CHB.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBeAg is glycosylated, which affects its secretion and immune modulation.", "mechanism": "HBeAg positivity indicates active viral replication and infectivity in CHB.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "As an IgG, anti-HBs is glycosylated, which affects its stability and effector functions.", "mechanism": "Anti-HBs positivity is associated with viral clearance and functional cure.", "protein": "Antibody to hepatitis B surface antigen (anti-HBs)", "relationship_type": "protective", "source_pmcid": "PMC12336920" }, { "confidence": "medium", "disease": "Lamivudine-resistant hepatitis B", "glycan_involvement": "Drug resistance mutations may impact glycosylation sites, affecting HBsAg secretion.", "mechanism": "Mutations in HBV polymerase (rtM204I) can affect the S gene, altering HBsAg secretion and detection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Lamivudine-resistant hepatitis B", "glycan_involvement": "Mutation can cause overlapping changes in HBsAg glycosylation due to gene overlap.", "mechanism": "rtM204I mutation in polymerase confers resistance to lamivudine, leading to treatment failure.", "protein": "HBV polymerase (reverse transcriptase)", "relationship_type": "causal", "source_pmcid": "PMC12336920" }, { "confidence": "medium", "disease": "HBV infection (vertical transmission)", "glycan_involvement": "Glycosylation of HBsAg is important for immune evasion and mother-to-child transmission.", "mechanism": "HBsAg positivity in infants indicates vertical transmission of HBV.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Glycosylation affects HBeAg secretion and immune tolerance.", "mechanism": "HBeAg clearance is a treatment endpoint indicating improved immune control.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Glycosylation modulates HBsAg antigenicity and clearance.", "mechanism": "HBsAg loss is a key marker of functional cure in CHB therapy.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336920" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Not glycosylated; included for completeness.", "mechanism": "HBcAg is used in research and diagnostics to assess infection and immune response.", "protein": "HBV core antigen (HBcAg)", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03146" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "IgG glycosylation affects antibody function.", "mechanism": "Early anti-HBs positivity predicts favorable prognosis and HBsAg clearance.", "protein": "Antibody to hepatitis B surface antigen (anti-HBs)", "relationship_type": "biomarker", "source_pmcid": "PMC12336920" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 is glycosylated; glycosylation affects its stability and detection.", "mechanism": "PD-L1 expression on tumor cells predicts response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337043" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-1 glycosylation may modulate receptor-ligand interactions.", "mechanism": "PD-1 is targeted by ICIs to block immune suppression and enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (lung)", "glycan_involvement": "Glycosylation may affect PD-L1 detection and function.", "mechanism": "Low PD-L1 expression correlates with poor response to ICIs in squamous cell carcinoma.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "Adenocarcinoma (lung)", "glycan_involvement": "Glycosylation impacts PD-L1 stability and antibody binding.", "mechanism": "PD-L1 expression is used to stratify adenocarcinoma patients for ICI therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "CTLA-4 glycosylation may influence its cell surface expression.", "mechanism": "CTLA-4 is targeted by antibodies (e.g., ipilimumab) to enhance T cell activation.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "EGFR is glycosylated; glycosylation affects receptor function.", "mechanism": "EGFR mutation status guides exclusion from ICI therapy due to alternative targeted treatments.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "VEGF-A is glycosylated, which may affect its secretion and activity.", "mechanism": "VEGF-A is targeted by bevacizumab to inhibit angiogenesis in NSCLC.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation can mask PD-L1 epitopes, affecting antibody binding.", "mechanism": "PD-L1 is targeted by atezolizumab and durvalumab to block immune evasion.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337043" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation stabilizes PD-L1 and enhances its immune suppressive function.", "mechanism": "PD-L1 on tumor cells suppresses T cell activity, promoting tumor immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12337043" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation may affect PD-L1 detection by immunohistochemistry.", "mechanism": "PD-L1-negative status (<1% TPS) is associated with limited efficacy of ICIs.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337043" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates PD-1 stability and ligand binding.", "mechanism": "PD-1 is targeted by pembrolizumab to enhance anti-tumor immunity.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337046" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation affects PD-L1 expression and immune recognition.", "mechanism": "PD-L1 is targeted by ICIs to block immune evasion by tumor cells.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337046" }, { "confidence": "medium", "disease": "Immune-related hepatitis", "glycan_involvement": "Glycosylation may influence PD-1 receptor function and immune activation.", "mechanism": "PD-1 blockade leads to loss of peripheral tolerance, causing hepatic autoimmunity.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "causal", "source_pmcid": "PMC12337046" }, { "confidence": "medium", "disease": "Immune-related thyroiditis", "glycan_involvement": "Glycosylation may modulate PD-1 signaling in immune cells.", "mechanism": "PD-1 inhibition triggers thyroid autoimmunity as an irAE.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "causal", "source_pmcid": "PMC12337046" }, { "confidence": "medium", "disease": "Immune-related hypophysitis", "glycan_involvement": "Glycosylation may affect PD-1 receptor trafficking and immune response.", "mechanism": "PD-1 blockade can induce pituitary inflammation via immune dysregulation.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "causal", "source_pmcid": "PMC12337046" }, { "confidence": "high", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "N-glycosylation is essential for IL-6R function and antibody binding.", "mechanism": "Tocilizumab (anti-IL-6R) is used to prevent or treat irAEs by blocking IL-6 signaling.", "protein": "IL-6 receptor (Interleukin-6 receptor subunit alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337046" }, { "confidence": "high", "disease": "Immune-related thyroiditis", "glycan_involvement": "TSH is a glycoprotein hormone; glycosylation is required for stability and activity.", "mechanism": "Elevated TSH indicates thyroid dysfunction due to immune-mediated injury.", "protein": "Thyroid stimulating hormone (TSH)", "protein_enriched": { "function": "Indispensable for the control of thyroid structure and metabolism", "gene_name": "TSHB", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G08185DV", "G14358WN", "G16122GW", "G24954RW", "G38217AM", "G41708PN", "G77198CF" ], "uniprot_id": "P01222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337046" }, { "confidence": "medium", "disease": "Adrenal insufficiency", "glycan_involvement": "ACTH glycosylation affects hormone secretion and bioactivity.", "mechanism": "Low ACTH reflects pituitary dysfunction (hypophysitis) leading to adrenal insufficiency.", "protein": "Adrenocorticotropic hormone (ACTH)", "protein_enriched": { "function": "Stimulates the adrenal glands to release cortisol", "gene_name": "POMC", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01189" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337046" }, { "confidence": "medium", "disease": "Immune-related hepatitis", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG used to modulate immune response in severe hepatitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337046" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "MET is a glycoprotein; glycosylation is required for proper folding and receptor function.", "mechanism": "MET amplification, mutation, or overexpression drives NSCLC progression via activation of proliferation and invasion pathways.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "causal", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "MET exon 14 skipping mutation NSCLC", "glycan_involvement": "Glycosylation affects MET receptor stability and ligand binding.", "mechanism": "MET ex14 skipping mutation leads to increased MET activity; capmatinib inhibits MET and is highly effective in this subtype.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "Brain metastases (BM)", "glycan_involvement": "Glycosylation may influence MET receptor trafficking and BBB permeability.", "mechanism": "Capmatinib targets MET, crosses the blood-brain barrier, and induces intracranial tumor regression in NSCLC patients with BM.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "EGFR-mutated NSCLC", "glycan_involvement": "EGFR glycosylation modulates receptor activation and drug sensitivity.", "mechanism": "EGFR mutations drive NSCLC; combination of EGFR and MET inhibitors (capmatinib + gefitinib) overcomes resistance.", "protein": "EGFR (Epidermal Growth Factor Receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "MET-amplified NSCLC", "glycan_involvement": "Glycosylation required for MET receptor function.", "mechanism": "MET amplification is a resistance mechanism in EGFR-mutant NSCLC; capmatinib plus EGFR TKIs is effective.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "HER3 glycosylation affects dimerization and signaling.", "mechanism": "HER3 pathway activation is downstream of MET; capmatinib inhibits MET and blocks HER3 signaling.", "protein": "HER3 (Human Epidermal Growth Factor Receptor 3)", "protein_enriched": { "function": "Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine", "gene_name": "ERBB3", "glycan_count": 21, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G27058EU", "G31852PQ", "G37399XV", "G41247ZX", "G59924QI", "G62765YT", "G70619PT", "G80920RR", "G18647XP", "G20210JR", "G23294PN", "G65184UU", "G87389XI", "G25451PN", "G07246CJ", "G70441OD", "G90659AW" ], "uniprot_id": "P21860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337076" }, { "confidence": "medium", "disease": "Brain metastases (BM)", "glycan_involvement": "P-gp glycosylation is essential for membrane localization and function.", "mechanism": "P-gp at BBB limits drug penetration; capmatinib inhibits P-gp, improving CNS drug delivery.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "medium", "disease": "Brain metastases (BM)", "glycan_involvement": "BCRP glycosylation affects transporter activity.", "mechanism": "BCRP at BBB restricts drug entry; capmatinib inhibits BCRP, enhancing brain exposure.", "protein": "BCRP (Breast Cancer Resistance Protein, ABCG2)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "Drug resistance in NSCLC", "glycan_involvement": "Glycosylation modulates MET receptor stability and signaling.", "mechanism": "MET amplification causes resistance to EGFR TKIs; targeting MET restores sensitivity.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "causal", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation status may affect MET detection and function.", "mechanism": "MET overexpression/amplification serves as a biomarker for MET TKI therapy selection.", "protein": "MET (Mesenchymal-epithelial transition factor)", "relationship_type": "biomarker", "source_pmcid": "PMC12337076" }, { "confidence": "high", "disease": "Hydatid disease (Echinococcosis)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Antigen B is released by hydatid cysts and detected in host serum for diagnosis.", "protein": "Echinococcus granulosus Antigen B", "protein_enriched": { "function": "", "gene_name": "xprt", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U6Y2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "high", "disease": "Hydatid disease (Echinococcosis)", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "Antigen 5 is a major immunogenic glycoprotein used in serological diagnosis.", "protein": "Echinococcus granulosus Antigen 5", "protein_enriched": { "function": "Odorant receptor which mediates acceptance or avoidance behavior, depending on its substrates. The odorant receptor repertoire encodes a large collection of odor stimuli that vary widely in identity, ", "gene_name": "Or59a", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P81923" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "high", "disease": "Hydatid disease (Echinococcosis)", "glycan_involvement": "Fc glycosylation affects antibody function and detection.", "mechanism": "IgG antibodies against hydatid antigens indicate infection.", "protein": "Serum Immunoglobulin G (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "N-glycosylation modulates CRP stability and function.", "mechanism": "CRP levels rise in response to infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "medium", "disease": "Inferior vena cava thrombosis", "glycan_involvement": "Glycosylation affects fibrinogen polymerization and clot stability.", "mechanism": "Fibrinogen is involved in clot formation during thrombosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12337654" }, { "confidence": "medium", "disease": "Inferior vena cava thrombosis", "glycan_involvement": "O-glycosylation regulates VWF multimerization and activity.", "mechanism": "VWF mediates platelet adhesion in vascular injury and thrombosis.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC12337654" }, { "confidence": "medium", "disease": "Hydatid cyst rupture", "glycan_involvement": "O-glycosylation provides protection against host enzymes.", "mechanism": "Mucin-like glycoproteins contribute to cyst wall integrity and immune evasion.", "protein": "Echinococcus granulosus mucin-like glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12337654" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Glycosylation modulates anti-inflammatory properties.", "mechanism": "AGP is an acute-phase reactant elevated in infection.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "low", "disease": "Systemic hydatidosis", "glycan_involvement": "N-glycosylation changes in infection.", "mechanism": "Altered transferrin glycoforms may reflect chronic infection.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "low", "disease": "Hydatid disease (Echinococcosis)", "glycan_involvement": "Minor glycosylation, limited impact.", "mechanism": "Serum albumin may decrease in chronic infection.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337654" }, { "confidence": "high", "disease": "Acute pain", "glycan_involvement": "Na v 1.8 is a glycoprotein; glycosylation affects channel trafficking and function.", "mechanism": "Suzetrigine selectively inhibits Na v 1.8 in peripheral nociceptors, reducing pain signaling.", "protein": "Na v 1.8 (SCN10A)", "protein_enriched": { "function": "Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across ", "gene_name": "SCN10A", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Y9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337992" }, { "confidence": "high", "disease": "Postoperative pain", "glycan_involvement": "Glycosylation modulates channel localization and drug sensitivity.", "mechanism": "Suzetrigine blocks Na v 1.8, providing analgesia in surgical pain models.", "protein": "Na v 1.8 (SCN10A)", "protein_enriched": { "function": "Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across ", "gene_name": "SCN10A", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Y9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Musculoskeletal pain", "glycan_involvement": "Glycosylation may influence channel expression in muscle afferents.", "mechanism": "Peripheral Na v 1.8 inhibition by suzetrigine alleviates acute musculoskeletal pain.", "protein": "Na v 1.8 (SCN10A)", "protein_enriched": { "function": "Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across ", "gene_name": "SCN10A", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Y9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "Altered glycosylation in diabetes may affect channel function.", "mechanism": "Ongoing trials for suzetrigine in chronic neuropathic pain via Na v 1.8 blockade.", "protein": "Na v 1.8 (SCN10A)", "protein_enriched": { "function": "Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across ", "gene_name": "SCN10A", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Y9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Drug-induced toxicity", "glycan_involvement": "N-glycosylation is critical for transporter function.", "mechanism": "P-glycoprotein limits CNS penetration of suzetrigine, reducing central side effects.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation modulates OATP1B1 substrate specificity.", "mechanism": "Suzetrigine inhibits OATP1B1, potentially affecting hepatic drug clearance.", "protein": "OATP1B1 (SLCO1B1)", "protein_enriched": { "function": "Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taur", "gene_name": "SLCO1B1", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G34989PA", "G90659AW" ], "uniprot_id": "Q9Y6L6" }, "relationship_type": "causal", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Hepatic impairment", "glycan_involvement": "Glycosylation affects transporter stability and function.", "mechanism": "Suzetrigine and its metabolite inhibit OATP1B3, impacting hepatic drug transport.", "protein": "OATP1B3 (SLCO1B3)", "protein_enriched": { "function": "Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting ins", "gene_name": "ACKR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NPB9" }, "relationship_type": "causal", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Renal impairment", "glycan_involvement": "Glycosylation required for proper OAT3 localization.", "mechanism": "Suzetrigine inhibits OAT3, potentially altering renal drug excretion.", "protein": "OAT3 (SLC22A8)", "protein_enriched": { "function": "Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP", "gene_name": "CYTH4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIA0" }, "relationship_type": "causal", "source_pmcid": "PMC12337992" }, { "confidence": "low", "disease": "Drug-induced toxicity", "glycan_involvement": "N-glycosylation essential for BCRP function.", "mechanism": "Suzetrigine is not a BCRP substrate, reducing risk of transporter-mediated toxicity.", "protein": "BCRP (ABCG2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12337992" }, { "confidence": "medium", "disease": "Opioid addiction", "glycan_involvement": "Glycosylation maintains transporter activity.", "mechanism": "Limited CNS penetration via P-glycoprotein reduces abuse potential of suzetrigine.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12337992" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation affects complement stability and function.", "mechanism": "Complement activation and consumption reflect immune complex deposition and disease activity.", "protein": "Complement proteins (C3, C4)", "relationship_type": "biomarker", "source_pmcid": "PMC12338000" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "Autoantibodies form immune complexes, driving tissue inflammation.", "protein": "Immunoglobulins (IgG, IgM)", "relationship_type": "causal", "source_pmcid": "PMC12338000" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated serum lipase indicates pancreatic inflammation.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338000" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "N-glycosylation affects enzyme activity.", "mechanism": "Elevated serum amylase is a diagnostic marker for pancreatitis.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12338000" }, { "confidence": "medium", "disease": "Acute pancreatitis (SLE-related)", "glycan_involvement": "Glycosylation of autoantibodies influences pathogenicity.", "mechanism": "Autoantibodies target pancreatic tissue, leading to inflammation.", "protein": "Anti-pancreatic antibodies", "relationship_type": "causal", "source_pmcid": "PMC12338000" }, { "confidence": "medium", "disease": "Acute pancreatitis (SLE-related)", "glycan_involvement": "N-glycosylation modulates complement activation.", "mechanism": "Complement activation contributes to pancreatic ischemia and inflammation.", "protein": "Complement proteins (C3, C4)", "relationship_type": "causal", "source_pmcid": "PMC12338000" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "N-glycosylation affects serum half-life.", "mechanism": "Hypoalbuminemia reflects severity of inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338000" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "N-glycosylation influences enzyme stability.", "mechanism": "Elevated LDH indicates tissue damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338000" }, { "confidence": "low", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "May alter glycosylation of immune proteins.", "mechanism": "Hydroxychloroquine modulates immune glycoproteins, reducing disease activity.", "protein": "Hydroxychloroquine-modulated proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338000" }, { "confidence": "medium", "disease": "Acute pancreatitis (SLE-related)", "glycan_involvement": "Fc glycosylation affects immune complex formation.", "mechanism": "Autoantibodies may contribute to pancreatic inflammation.", "protein": "Immunoglobulins (IgG, IgM)", "relationship_type": "causal", "source_pmcid": "PMC12338000" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation is essential for complex stability and membrane localization.", "mechanism": "Loss or dysfunction of dystrophin glycoprotein complex leads to contraction-induced muscle injury and progressive muscle degeneration.", "protein": "Dystrophin glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12338012" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation defects can exacerbate membrane instability.", "mechanism": "Absence of functional dystrophin glycoprotein complex causes severe muscle damage and degeneration.", "protein": "Dystrophin glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12338012" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "CK is glycosylated, affecting stability and secretion.", "mechanism": "Elevated serum CK indicates ongoing muscle injury in BMD; levels decrease with sevasemten treatment.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation may regulate plasma stability.", "mechanism": "Elevated plasma TNNI2 reflects fast fiber-specific muscle injury; reduced by sevasemten.", "protein": "Fast skeletal muscle troponin I (TNNI2)", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation influences myoglobin solubility and clearance.", "mechanism": "Elevated myoglobin in plasma is a marker of muscle injury; reduced by sevasemten.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "medium", "disease": "MYH2 deficiency", "glycan_involvement": "Glycosylation may affect myosin assembly and function.", "mechanism": "Genetic absence of MYH2 leads to muscle weakness, especially in ocular, facial, and proximal limb muscles.", "protein": "MYH2 (Myosin heavy chain 2)", "relationship_type": "causal", "source_pmcid": "PMC12338012" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation modulates immune protein function and clearance.", "mechanism": "Elevated immune/inflammatory glycoproteins in plasma reflect chronic muscle inflammation in BMD.", "protein": "Immune/inflammatory proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "N-glycosylation regulates VEGF secretion and activity.", "mechanism": "VEGF is part of the globally lower protein set in BMD plasma, indicating altered muscle vascularization.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "N-glycosylation affects EGF receptor binding.", "mechanism": "EGF is reduced in BMD plasma, suggesting impaired muscle regeneration signaling.", "protein": "Epidermal growth factor (EGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "N-glycosylation modulates PDGF receptor interaction.", "mechanism": "PDGF is reduced in BMD plasma, indicating altered muscle repair processes.", "protein": "Platelet-derived growth factor (PDGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12338012" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates PD-1 stability and ligand binding.", "mechanism": "PD-1 inhibits T-cell activation; blockade restores anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338152" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for PD-L1 surface expression and immune evasion.", "mechanism": "PD-L1 binds PD-1 to suppress immune response; inhibition enhances anti-tumor activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338152" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation affects CTLA-4 trafficking and function.", "mechanism": "CTLA-4 inhibits early T-cell activation; blockade promotes anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation may influence PD-1 expression during infection.", "mechanism": "PD-1 upregulation in chronic viral infection leads to T-cell exhaustion.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation stabilizes PD-L1, enhancing immune evasion.", "mechanism": "PD-L1 expression increases in viral infection, contributing to immune suppression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding and infectivity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "Glycosylation status may affect checkpoint protein function and irAE risk.", "mechanism": "Blockade of immune checkpoints can trigger irAEs via immune overactivation.", "protein": "PD-1/PD-L1/CTLA-4", "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "Pneumonitis", "glycan_involvement": "Glycosylation may modulate checkpoint protein stability and immune response.", "mechanism": "ICI-induced immune activation can cause lung inflammation.", "protein": "PD-1/PD-L1/CTLA-4", "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation may influence checkpoint protein-mediated immune activation.", "mechanism": "Excessive immune activation by ICIs may precipitate ARDS in COVID-19.", "protein": "PD-1/PD-L1/CTLA-4", "relationship_type": "causal", "source_pmcid": "PMC12338152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects checkpoint protein function and therapeutic efficacy.", "mechanism": "ICI therapy may enhance anti-viral immunity and facilitate viral clearance.", "protein": "PD-1/PD-L1/CTLA-4", "relationship_type": "protective", "source_pmcid": "PMC12338152" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Protein S is a glycoprotein; glycosylation may affect stability and function in tumor microenvironment.", "mechanism": "Low expression associated with poor overall survival and progression-free survival; linked to advanced tumor stage, lymph node metastasis, and larger tumor size.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Clusterin is heavily glycosylated; glycosylation influences isoform function and cellular localization.", "mechanism": "Low or moderate expression correlates with high-risk clinicopathologic features (extrathyroidal extension, multifocality, advanced stage, lymph node metastasis) and poor prognosis.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "LRG1 is a glycoprotein; glycosylation may modulate its role in cell adhesion and immune response.", "mechanism": "Low or moderate expression is associated with advanced stage, poor clinicopathologic outcomes, and worse progression-free survival.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation affects clusterin's anti-apoptotic and chaperone functions.", "mechanism": "High expression is protective, associated with better prognosis and progression-free survival.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may regulate LRG1's interaction with TGF\u03b21 and cell signaling.", "mechanism": "High expression inhibits tumor progression and is linked to improved survival.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "protective", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may influence Protein S's ligand-receptor interactions in tumor microenvironment.", "mechanism": "High expression correlates with better progression-free survival and less aggressive disease.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12338188" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may affect CLU's isoform distribution and function.", "mechanism": "Negative correlation between CLU expression and BRAF mutation, which is associated with poor prognosis.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may modulate LRG1's role in cell signaling.", "mechanism": "Negative correlation (not significant) between LRG1 expression and BRAF mutation.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may affect Protein S's stability and function.", "mechanism": "Low expression is associated with higher tumor classification and advanced AJCC stage.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation influences CLU's anti-metastatic properties.", "mechanism": "Low expression is associated with lymph node metastasis and larger tumor size.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338188" }, { "confidence": "high", "disease": "Sleep disorder", "glycan_involvement": "IgG is N-glycosylated; glycosylation affects antibody function and immune modulation.", "mechanism": "Serum IgG levels are altered in sleep disorder; increased after therapy indicates improved immune status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "high", "disease": "Sleep disorder", "glycan_involvement": "IgA is N-glycosylated; glycosylation modulates mucosal immunity.", "mechanism": "Serum IgA levels increase with effective sleep disorder therapy, reflecting immune improvement.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "high", "disease": "Sleep disorder", "glycan_involvement": "IgM is N-glycosylated; glycosylation affects pentamer formation and immune response.", "mechanism": "Serum IgM levels increase after intervention, indicating immune system activation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Altered glycosylation can impair IgG function.", "mechanism": "Low IgG levels indicate immunodeficiency, which may be exacerbated by sleep disorder.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "Glycosylation is essential for IgA's mucosal protective function.", "mechanism": "IgA protects against infection; increased levels after sleep therapy suggest improved resistance.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12338216" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation modulates IgG effector functions in autoimmunity.", "mechanism": "IgG levels and glycosylation patterns are altered in autoimmune diseases, which may be influenced by sleep quality.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "high", "disease": "Insomnia", "glycan_involvement": "N-glycosylation affects IgG stability and function.", "mechanism": "IgG levels are altered in insomnia; therapy increases IgG, reflecting improved immunity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "high", "disease": "Insomnia", "glycan_involvement": "N-glycosylation is critical for IgA's immune role.", "mechanism": "IgA levels increase after insomnia therapy, indicating immune recovery.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "high", "disease": "Insomnia", "glycan_involvement": "N-glycosylation required for IgM structure and function.", "mechanism": "IgM levels rise after insomnia therapy, reflecting immune activation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338216" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "Glycosylation modulates IgG's pathogen binding and clearance.", "mechanism": "IgG binds pathogens; increased levels after sleep therapy suggest enhanced protection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12338216" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Mediates multidrug resistance by efflux of chemotherapeutic agents (e.g., doxorubicin) from cancer cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation affects drug binding and transporter function.", "mechanism": "Targeting P-gp may overcome chemoresistance, but clinical utility as a predictive biomarker is limited.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates efflux activity.", "mechanism": "High P-gp expression associated with poor prognosis and chemoresistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Childhood soft-tissue sarcoma", "glycan_involvement": "Glycosylation required for function.", "mechanism": "High P-gp expression correlates with poor prognosis and chemoresistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "low", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "No significant correlation between P-gp expression and prognosis or chemoresistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "low", "disease": "Ovarian carcinoma", "glycan_involvement": "Not specified.", "mechanism": "No significant correlation between P-gp expression and prognosis or chemoresistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation required for transporter activity.", "mechanism": "Contributes to multidrug resistance via drug efflux.", "protein": "Multidrug resistance-associated protein 1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation required for transporter activity.", "mechanism": "Contributes to multidrug resistance via drug efflux.", "protein": "Breast cancer resistance protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338221" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation essential for membrane localization and function.", "mechanism": "Promotes drug resistance and tumor progression by reducing intracellular drug concentration.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12338221" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation status not directly assessed in this study.", "mechanism": "Pretreatment P-gp immunostaining does not reliably predict chemotherapy efficacy or survival.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338221" }, { "confidence": "high", "disease": "OSAS", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "Lower ADMA levels in early OSAS reflect compensatory NO synthesis and vascular protection.", "protein": "ADMA", "relationship_type": "biomarker", "source_pmcid": "PMC12338228" }, { "confidence": "high", "disease": "OSAS", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "Lower L-NMMA in OSAS indicates metabolic shift toward NO production.", "protein": "L-NMMA", "relationship_type": "biomarker", "source_pmcid": "PMC12338228" }, { "confidence": "medium", "disease": "OSAS", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "SDMA levels remain unchanged in OSAS, suggesting limited involvement in early disease.", "protein": "SDMA", "relationship_type": "biomarker", "source_pmcid": "PMC12338228" }, { "confidence": "medium", "disease": "Pulmonary arterial hypertension", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "Elevated ADMA associated with endothelial dysfunction and disease complications.", "protein": "ADMA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12338228" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "Higher ADMA in COPD reflects chronic hypoxia and oxidative stress.", "protein": "ADMA", "relationship_type": "biomarker", "source_pmcid": "PMC12338228" }, { "confidence": "high", "disease": "OSAS", "glycan_involvement": "No direct glycosylation; enzyme activity is key.", "mechanism": "Increased DDAH activity in early OSAS degrades ADMA, promoting NO synthesis and vascular protection.", "protein": "DDAH", "relationship_type": "protective", "source_pmcid": "PMC12338228" }, { "confidence": "high", "disease": "OSAS", "glycan_involvement": "eNOS is a glycoprotein; glycosylation may affect stability and localization.", "mechanism": "Upregulated eNOS activity in early OSAS increases NO, counteracting hypoxia-induced vasoconstriction.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "protective", "source_pmcid": "PMC12338228" }, { "confidence": "medium", "disease": "OSAS", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "PRMTs methylate arginine, generating ADMA/L-NMMA; activity may be suppressed in early OSAS.", "protein": "PRMTs", "relationship_type": "causal", "source_pmcid": "PMC12338228" }, { "confidence": "high", "disease": "Vascular/endothelial dysfunction", "glycan_involvement": "No direct glycosylation; methylation is the key PTM.", "mechanism": "Elevated ADMA inhibits NOS, reducing NO and leading to endothelial dysfunction.", "protein": "ADMA", "relationship_type": "causal", "source_pmcid": "PMC12338228" }, { "confidence": "medium", "disease": "Atherogenesis", "glycan_involvement": "eNOS glycosylation may modulate enzyme activity and vascular protection.", "mechanism": "eNOS-derived NO inhibits platelet aggregation and prevents atherogenesis.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "protective", "source_pmcid": "PMC12338228" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 stability and receptor binding.", "mechanism": "Promotes hepatic insulin resistance and fat deposition, contributing to NAFLD pathogenesis in RA.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects IL-6 secretion and receptor interaction.", "mechanism": "Activates hepatic stellate cells, exacerbating liver inflammation and fibrosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation influences IL-1\u03b2 maturation and activity.", "mechanism": "Contributes to hepatic inflammation and progression to NASH.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 bioactivity.", "mechanism": "Drives chronic joint inflammation and systemic effects.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates IL-6 signaling.", "mechanism": "Promotes synovial inflammation and systemic features.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor interactions.", "mechanism": "Induces hepatic stellate cell activation and fibrogenesis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation influences IL-6 stability.", "mechanism": "Drives hepatic stellate cell activation and collagen deposition.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 half-life.", "mechanism": "Systemic inflammation increases cardiovascular risk in RA and NAFLD.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects IL-6 receptor binding.", "mechanism": "Elevated IL-6 promotes vascular inflammation and atherosclerosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation regulates IL-1\u03b2 secretion.", "mechanism": "Drives progression from NAFLD to NASH via hepatic inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12338258" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Altered N-glycosylation (galactosylation) serves as a disease marker.", "mechanism": "Decrease in galactosylation of IgG1 Fc N-glycans observed in lung cancer patients.", "protein": "IgG1 Fc", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Changes in sialylation and fucosylation of N-glycans.", "mechanism": "Increase of \u03b1(2\u20133)-sialic acid and decrease of core fucosylation in PSA N-glycans improves diagnosis.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "high", "disease": "Epithelial ovarian cancer", "glycan_involvement": "Altered N-glycan branching and sialylation patterns.", "mechanism": "Downregulation of high-mannose and upregulation of sialylated tri-/tetraantennary N-glycans, plus changes in sialic acid linkages.", "protein": "Glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "Changes in O-glycosylation (sulfation, sialylation) of mucins.", "mechanism": "Altered sulfation and sialylation of mucin-type O-glycans in sputum of cystic fibrosis patients.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Altered glycosylation patterns in glycoproteins.", "mechanism": "Changes in glycome composition associated with disease occurrence.", "protein": "Glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "medium", "disease": "Congenital diseases", "glycan_involvement": "N-glycosylation profile changes as disease markers.", "mechanism": "Glycomics used for early detection and quality control of glycosylated biopharmaceuticals.", "protein": "Monoclonal antibody", "relationship_type": "quality control/biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "high", "disease": "Influenza virus infection", "glycan_involvement": "Sialic acid linkage type on host glycoproteins is critical for viral binding.", "mechanism": "HA binds to sialylated glycans with specific \u03b1(2\u20133) or \u03b1(2\u20136) linkages, determining host susceptibility.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338385" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Global changes in glycosylation patterns.", "mechanism": "Altered glycome composition associated with lung cancer occurrence.", "protein": "Glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Global changes in glycosylation patterns.", "mechanism": "Altered glycome composition associated with prostate cancer occurrence.", "protein": "Glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "medium", "disease": "Congenital diseases", "glycan_involvement": "Altered glycosylation profiles in glycoproteins.", "mechanism": "Glycomics enables early detection of congenital glycosylation disorders.", "protein": "Glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12338385" }, { "confidence": "high", "disease": "El Bagre Endemic Pemphigus Foliaceus (El Bagre-EPF)", "glycan_involvement": "Dsg1 is a glycoprotein; glycosylation may affect antigenicity and autoantibody binding.", "mechanism": "Autoantibody targeting of Dsg1 disrupts desmosomal adhesion in skin.", "protein": "Desmoglein-1 (Dsg1)", "protein_enriched": { "function": "Component of intercellular desmosome junctions (PubMed:34368962). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:19717567)", "gene_name": "DSG1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q02413" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "high", "disease": "Pemphigus Foliaceus (PF)", "glycan_involvement": "Glycosylation modulates Dsg1 structure and immune recognition.", "mechanism": "Autoantibodies against Dsg1 lead to loss of cell-cell adhesion.", "protein": "Desmoglein-1 (Dsg1)", "protein_enriched": { "function": "Component of intercellular desmosome junctions (PubMed:34368962). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:19717567)", "gene_name": "DSG1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q02413" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "medium", "disease": "Severe Dermatitis, Multiple Allergies, and Metabolic Wasting Syndrome (SAM syndrome)", "glycan_involvement": "Altered glycosylation may contribute to protein misfolding.", "mechanism": "Mutations in Dsg1 disrupt epidermal barrier function.", "protein": "Desmoglein-1 (Dsg1)", "protein_enriched": { "function": "Component of intercellular desmosome junctions (PubMed:34368962). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:19717567)", "gene_name": "DSG1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q02413" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "medium", "disease": "Palmoplantar Keratoderma", "glycan_involvement": "Glycosylation status may affect Dsg1 stability.", "mechanism": "Dsg1 mutations cause abnormal keratinization.", "protein": "Desmoglein-1 (Dsg1)", "protein_enriched": { "function": "Component of intercellular desmosome junctions (PubMed:34368962). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:19717567)", "gene_name": "DSG1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q02413" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "high", "disease": "Carvajal/Naxos Syndrome", "glycan_involvement": "DSP is a glycoprotein; glycosylation may influence desmosome assembly.", "mechanism": "DSP mutations impair desmosomal integrity in skin and heart.", "protein": "Desmoplakin (DSP)", "protein_enriched": { "function": "Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundan", "gene_name": "DSP", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G94310CV", "G31852PQ" ], "uniprot_id": "P15924" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "high", "disease": "Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)", "glycan_involvement": "Glycosylation may modulate DSP interactions in cardiac tissue.", "mechanism": "DSP mutations disrupt cardiac desmosomes, leading to arrhythmia.", "protein": "Desmoplakin (DSP)", "protein_enriched": { "function": "Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundan", "gene_name": "DSP", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G94310CV", "G31852PQ" ], "uniprot_id": "P15924" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "medium", "disease": "Epidermolysis Bullosa", "glycan_involvement": "Glycosylation may affect DSP stability and function.", "mechanism": "DSP mutations weaken skin adhesion.", "protein": "Desmoplakin (DSP)", "protein_enriched": { "function": "Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundan", "gene_name": "DSP", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G94310CV", "G31852PQ" ], "uniprot_id": "P15924" }, "relationship_type": "causal", "source_pmcid": "PMC12339050" }, { "confidence": "low", "disease": "Alzheimer Disease", "glycan_involvement": "BP230 glycosylation may influence neuronal interactions.", "mechanism": "BP230 isoform 9 interacts with TMEM108, associated with Alzheimer pathology.", "protein": "Bullous Pemphigoid Antigen 1 (BP230)", "protein_enriched": { "function": "", "gene_name": "DST", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q03001-7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339050" }, { "confidence": "medium", "disease": "Paraneoplastic Pemphigus (PNP)", "glycan_involvement": "Glycosylation may affect EVPL antigenicity.", "mechanism": "EVPL is a recognized autoantigen in PNP.", "protein": "Envoplakin (EVPL)", "protein_enriched": { "function": "Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments", "gene_name": "EVPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92817" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339050" }, { "confidence": "medium", "disease": "El Bagre Endemic Pemphigus Foliaceus (El Bagre-EPF)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "PPL is targeted by autoantibodies in El Bagre-EPF.", "protein": "Periplakin (PPL)", "protein_enriched": { "function": "Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling", "gene_name": "PPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60437" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339050" }, { "confidence": "high", "disease": "Hidradenitis Suppurativa", "glycan_involvement": "Glycosylation of adalimumab (IgG1 Fc region) is essential for stability and effector function.", "mechanism": "Adalimumab binds and neutralizes TNF-\u03b1, reducing inflammation in HS.", "protein": "Adalimumab", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339123" }, { "confidence": "medium", "disease": "Drug-Induced Liver Injury (DILI)", "glycan_involvement": "Glycosylation may affect immunogenicity and clearance, potentially influencing DILI risk.", "mechanism": "Idiosyncratic immune-mediated hepatocellular injury following adalimumab administration.", "protein": "Adalimumab", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12339123" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Fc glycosylation modulates antibody effector functions and immune response.", "mechanism": "Aberrant immune activation due to TNF-\u03b1 blockade leads to hepatic inflammation.", "protein": "Adalimumab", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12339123" }, { "confidence": "high", "disease": "Hidradenitis Suppurativa", "glycan_involvement": "TNF-\u03b1 is glycosylated, which may affect its stability and receptor binding.", "mechanism": "TNF-\u03b1 is a key pro-inflammatory cytokine driving HS pathology.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339123" }, { "confidence": "medium", "disease": "Drug-Induced Liver Injury (DILI)", "glycan_involvement": "No direct glycan involvement in biomarker function.", "mechanism": "Elevated transaminases serve as biomarkers for adalimumab-induced DILI.", "protein": "Adalimumab", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339123" }, { "confidence": "high", "disease": "Acute lymphoblastic leukemia (ALL)", "glycan_involvement": "PEGylation (glycan modification) increases half-life and reduces immunogenicity", "mechanism": "Depletes extracellular asparagine, inhibiting ALL cell proliferation", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339246" }, { "confidence": "high", "disease": "Hepatotoxicity (transaminitis, hyperbilirubinemia)", "glycan_involvement": "PEGylation may alter immune response and toxicity profile", "mechanism": "Induces liver injury via asparagine depletion and mitochondrial dysfunction", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "causal", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Not directly discussed", "mechanism": "Reduces antithrombin III and other coagulation factors, increasing thrombotic risk", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "causal", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "Not directly discussed", "mechanism": "Alters amino acid metabolism, predisposing to pancreatic inflammation", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "causal", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "Not directly discussed", "mechanism": "Disrupts lipid metabolism, leading to elevated triglycerides", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "causal", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Not directly discussed", "mechanism": "Induces coagulopathy via depletion of coagulation factors", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "causal", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not directly discussed", "mechanism": "Obesity increases risk of asparaginase-induced hepatotoxicity", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "risk_modifier", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Hepatotoxicity (transaminitis, hyperbilirubinemia)", "glycan_involvement": "Not discussed", "mechanism": "SOD2 rs4880-CC genotype increases susceptibility to asparaginase-induced liver injury", "protein": "Superoxide dismutase 2 (SOD2)", "protein_enriched": { "function": "Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G30740WO", "G35253PZ" ], "uniprot_id": "P04179" }, "relationship_type": "risk_modifier", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Hepatotoxicity (transaminitis, hyperbilirubinemia)", "glycan_involvement": "Not directly discussed", "mechanism": "Hispanic ethnicity associated with higher risk of hepatotoxicity, possibly due to genetic and metabolic factors", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "risk_modifier", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Hepatotoxicity (transaminitis, hyperbilirubinemia)", "glycan_involvement": "Not directly discussed", "mechanism": "High asparaginase dose (>3750 units) increases risk of hepatotoxicity", "protein": "Asparaginase (PEG-asparaginase)", "protein_enriched": { "function": "", "gene_name": "ansB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00805" }, "relationship_type": "risk_modifier", "source_pmcid": "PMC12339246" }, { "confidence": "medium", "disease": "Early Kidney Injury", "glycan_involvement": "N-glycosylation required for cell surface expression and function.", "mechanism": "Upregulated in proximal tubular injury; undetectable in healthy tissue but increases in kidney injury.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "Early Kidney Injury", "glycan_involvement": "N-glycosylation affects secretion and anti-inflammatory function.", "mechanism": "Downregulated in systemic inflammation and early CKD; lower levels indicate inflammation-related renal damage.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "Early Kidney Injury", "glycan_involvement": "N-glycosylation modulates stability and secretion.", "mechanism": "Upregulated in response to tubular injury and inflammation; early marker for kidney damage.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "Early Kidney Injury", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Elevated in CHB patients before rise in creatinine; sensitive marker for early renal dysfunction.", "protein": "Cystatin-C", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "medium", "disease": "Early Kidney Injury", "glycan_involvement": "N-glycosylation required for secretion and binding affinity.", "mechanism": "Upregulated as anti-inflammatory response to neutralize IL-18; associated with renal damage.", "protein": "IL-18BP", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "CHB", "glycan_involvement": "N-glycosylation impacts anti-inflammatory activity.", "mechanism": "Downregulated in CHB patients, reflecting systemic inflammation.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "CHB", "glycan_involvement": "N-glycosylation modulates secretion.", "mechanism": "Elevated in CHB, indicating inflammation and risk for kidney injury.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "medium", "disease": "HBV-mediated Nephropathy", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Upregulated in HBV-induced tubular injury.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "medium", "disease": "CHB", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Elevated in CHB as host response to inflammation.", "protein": "IL-18BP", "relationship_type": "biomarker", "source_pmcid": "PMC12339531" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "N-glycosylation required for anti-inflammatory activity.", "mechanism": "Higher levels enhance renal function due to anti-inflammatory effects.", "protein": "Fetuin-A", "relationship_type": "protective", "source_pmcid": "PMC12339531" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "N-glycosylation is essential for LRG secretion and stability.", "mechanism": "LRG is induced by inflammatory cytokines and used to assess disease activity.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "SAA is glycosylated, affecting its solubility and immune interactions.", "mechanism": "SAA is an acute-phase reactant elevated during inflammation; involved in immunomodulation.", "protein": "Serum amyloid A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "IgE N-glycosylation modulates effector functions and receptor binding.", "mechanism": "IgE levels reflect Th2 cytokine activity; IL-4 induces IgE synthesis.", "protein": "Immunoglobulin E", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. 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"G76464YC", "G81315DD", "G82020ZR", "G89319AW", "G94626GC", "G97616MU", "G98940JV", "G67506FN", "G83295QG", "G39595FH", "G03127AL", "G04909DG", "G06356OH", "G10471FG", "G11041DA", "G12708JQ", "G23453IV", "G27993JQ", "G29880MM", "G42358LZ", "G47909JD", "G48414YA", "G49874UX", "G56749GV", "G56903ZB", "G60145BJ", "G61937QU", "G66760KM", "G68698AP", "G75798PH", "G80966KZ", "G81295CK", "G94854LT", "G95368PR" ], "uniprot_id": "P01854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "N-glycosylation required for LRG function.", "mechanism": "LRG is used to monitor disease activity in CD.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "N-glycosylation required for LRG function.", "mechanism": "LRG is used to monitor disease activity in UC.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation affects SAA immune interactions.", "mechanism": "SAA is elevated during active inflammation in CD.", "protein": "Serum amyloid A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation affects SAA immune interactions.", "mechanism": "SAA is elevated during active inflammation in UC.", "protein": "Serum amyloid A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "N-glycosylation modulates IgE function.", "mechanism": "IgE reflects Th2 activity, but not significantly correlated with Th1/Th2 ratio in CD.", "protein": "Immunoglobulin E", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. 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In the recognition phase of humoral i", "gene_name": "IGHE", "glycan_count": 106, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02030ZB", "G03382KH", "G05850WN", "G08146BT", "G11629QQ", "G22140GZ", "G22310AV", "G23863VK", "G25379SA", "G27102CT", "G31596VW", "G32246SI", "G34617SM", "G43157UW", "G45495MK", "G45883VE", "G50045TK", "G57818FI", "G61627IG", "G64394MX", "G65219TP", "G68209WQ", "G70375MX", "G79568CQ", "G79939YZ", "G81263BG", "G84452RH", "G89098OM", "G90093AU", "G91473PK", "G91636VS", "G97268YK", "G10256JP", "G24954UD", "G46687AB", "G57888GL", "G65186XA", "G72797UR", "G92129PT", "G50757KG", "G70418MS", "G72667IM", "G82592ZH", "G06110VR", "G10773YW", "G34730YF", "G55220VL", "G82119TF", "G02402FF", "G02815KT", "G03717EM", "G05724UK", "G07617FP", "G09724ZC", "G10756ZZ", "G14669DU", "G22573RC", "G22768VO", "G26624YG", "G33609NS", "G34059IB", "G34442SS", "G39188ZX", "G39617JJ", "G48626HI", "G54059XR", "G56014GC", "G63628AV", "G64527OM", "G66538GV", "G66676MI", "G70101JE", "G76464YC", "G81315DD", "G82020ZR", "G89319AW", "G94626GC", "G97616MU", "G98940JV", "G67506FN", "G83295QG", "G39595FH", "G03127AL", "G04909DG", "G06356OH", "G10471FG", "G11041DA", "G12708JQ", "G23453IV", "G27993JQ", "G29880MM", "G42358LZ", "G47909JD", "G48414YA", "G49874UX", "G56749GV", "G56903ZB", "G60145BJ", "G61937QU", "G66760KM", "G68698AP", "G75798PH", "G80966KZ", "G81295CK", "G94854LT", "G95368PR" ], "uniprot_id": "P01854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339904" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "N-glycosylation modulates IgE function.", "mechanism": "IgE reflects Th2 activity, but not significantly correlated with Th1/Th2 ratio in UC.", "protein": "Immunoglobulin E", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. 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Thought to act as an inhibitor of bone formation", "gene_name": "MGP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08493" }, "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates binding and activity", "mechanism": "Vitamin K activates vitronectin, inhibiting vascular calcification and atherosclerosis progression", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation affects ECM structure and signaling", "mechanism": "Vitamin D maintains homeostasis of ECM glycoproteins in cardiomyocytes, protecting against HF", "protein": "Extracellular Matrix Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation modulates immune cell function", "mechanism": "Vitamin B6 inhibits phenotypic changes in cardiac macrophages, reducing HF risk", "protein": "Cardiac Macrophage Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation and \u03b3-carboxylation required for activity", "mechanism": "Vitamin K-dependent activation of MGP reduces HF risk by preventing vascular calcification", "protein": "Matrix Gla Protein (MGP)", "protein_enriched": { "function": "Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation", "gene_name": "MGP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08493" }, "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Cardiac Hypertrophy", "glycan_involvement": "Altered glycosylation affects ECM integrity", "mechanism": "Vitamin D deficiency leads to ECM remodeling, promoting hypertrophy", "protein": "Extracellular Matrix Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation modulates endothelial cell interactions", "mechanism": "Vitamin D deficiency induces endothelial dysfunction via ECM glycoprotein changes", "protein": "Extracellular Matrix Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for proper folding and function", "mechanism": "Vitamin K-dependent activation of MGP inhibits atherosclerosis progression", "protein": "Matrix Gla Protein (MGP)", "protein_enriched": { "function": "Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation", "gene_name": "MGP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08493" }, "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation affects ECM signaling and immune modulation", "mechanism": "Vitamin A regulates ECM glycoprotein expression, reducing inflammation and HF risk", "protein": "Extracellular Matrix Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation influences macrophage phenotype and function", "mechanism": "Vitamin B6 modulates glycoprotein-mediated immune responses in cardiac tissue", "protein": "Cardiac Macrophage Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12340263" }, { "confidence": "high", "disease": "Abdominal aortic calcification (AAC)", "glycan_involvement": "HDL-C is a glycoprotein; glycosylation affects its structure and anti-inflammatory function.", "mechanism": "HDL-C exhibits anti-inflammatory and antioxidant properties, inhibits monocyte migration and inflammatory mediator release, reducing vascular calcification risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12340354" }, { "confidence": "high", "disease": "Abdominal aortic calcification (AAC)", "glycan_involvement": "Surface glycoproteins mediate adhesion and migration; glycosylation regulates monocyte-endothelial interactions.", "mechanism": "Monocytes migrate to arterial intima, differentiate into macrophages, and promote foam cell formation and plaque instability, contributing to calcification.", "protein": "Monocyte surface glycoproteins (generic)", "relationship_type": "causal", "source_pmcid": "PMC12340354" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates HDL-C's anti-inflammatory activity.", "mechanism": "HDL-C facilitates reverse cholesterol transport and reduces inflammation, slowing atherosclerotic progression.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12340354" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects monocyte recruitment and activation.", "mechanism": "Monocyte-derived macrophages drive plaque formation and instability.", "protein": "Monocyte surface glycoproteins (generic)", "relationship_type": "causal", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation influences HDL-C function.", "mechanism": "HDL-C reduces inflammation and oxidative stress, lowering coronary artery disease risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation modulates monocyte activity.", "mechanism": "Elevated monocyte count is associated with increased risk and poor outcomes.", "protein": "Monocyte surface glycoproteins (generic)", "relationship_type": "biomarker", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation impacts HDL-C stability and function.", "mechanism": "HDL-C's anti-inflammatory effects may reduce heart failure risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Abdominal aortic calcification (AAC)", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects its secretion and activity.", "mechanism": "IL-6 promotes vascular calcification under inflammatory conditions.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Abdominal aortic calcification (AAC)", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and signaling.", "mechanism": "TNF-\u03b1 upregulation drives vascular calcification via inflammation.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12340354" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation changes in diabetes may impair HDL-C function.", "mechanism": "Reduced HDL-C is associated with increased diabetes risk and vascular complications.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12340354" }, { "confidence": "high", "disease": "Anti-MAG neuropathy", "glycan_involvement": "MAG is highly glycosylated; autoantibodies target glycan epitopes.", "mechanism": "Anti-MAG IgM autoantibodies bind MAG, causing demyelination and sensory neuropathy.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "Anti-SGPG neuropathy", "glycan_involvement": "SGPG is a sulfated glycan; antibody binding disrupts nerve function.", "mechanism": "Anti-SGPG IgM autoantibodies bind SGPG, leading to demyelinating neuropathy.", "protein": "Sulfated glucuronyl paragloboside (SGPG)", "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "CANOMAD", "glycan_involvement": "MAG glycosylation is relevant for antibody recognition.", "mechanism": "Absence of anti-MAG antibodies helps differentiate CANOMAD from anti-MAG neuropathy.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "medium", "disease": "CANOMAD", "glycan_involvement": "SGPG glycan epitopes cross-react with antibodies found in CANOMAD.", "mechanism": "Anti-SGPG antibodies may be present in CANOMAD, risking misdiagnosis.", "protein": "Sulfated glucuronyl paragloboside (SGPG)", "relationship_type": "misleading biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "CANOMAD", "glycan_involvement": "GQ1b is a sialylated glycan; antibody binding affects cranial nerves.", "mechanism": "Anti-GQ1b IgM antibodies are characteristic of CANOMAD, associated with ophthalmoplegia.", "protein": "GQ1b ganglioside", "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "medium", "disease": "CANOMAD", "glycan_involvement": "Glycosylation of erythrocyte membrane proteins is essential for cold agglutinin binding.", "mechanism": "Cold agglutinins (IgM) bind erythrocyte glycoproteins, present in CANOMAD.", "protein": "Cold agglutinin target glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "Sensory ataxic neuropathy with IgM paraproteinemia", "glycan_involvement": "MAG glycosylation is targeted by autoantibodies.", "mechanism": "Anti-MAG antibodies are frequently found in sensory ataxic neuropathy with IgM paraproteinemia.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "Sensory ataxic neuropathy with IgM paraproteinemia", "glycan_involvement": "SGPG glycan structure is the antibody target.", "mechanism": "Anti-SGPG antibodies are frequently found in sensory ataxic neuropathy with IgM paraproteinemia.", "protein": "Sulfated glucuronyl paragloboside (SGPG)", "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "CANOMAD", "glycan_involvement": "Sialylated glycan of GQ1b is essential for antibody binding.", "mechanism": "Anti-GQ1b antibodies cause ophthalmoplegia by targeting cranial nerve gangliosides.", "protein": "GQ1b ganglioside", "relationship_type": "causal", "source_pmcid": "PMC12340380" }, { "confidence": "medium", "disease": "CANOMAD", "glycan_involvement": "Glycosylation of erythrocyte membrane proteins mediates agglutinin binding.", "mechanism": "Cold agglutinin positivity supports CANOMAD diagnosis.", "protein": "Cold agglutinin target glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12340380" }, { "confidence": "high", "disease": "Native vertebral osteomyelitis (NVO)", "glycan_involvement": "CRP is a glycoprotein; 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healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "protective", "source_pmcid": "PMC12340560" }, { "confidence": "high", "disease": "Traumatic brain injury", "glycan_involvement": "Glycosylation required for neuroprotective effects.", "mechanism": "PGRN suppresses microglial activation and neuroinflammation.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "protective", "source_pmcid": "PMC12340560" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "PSA is produced by prostate epithelial cells; elevated serum levels indicate prostate cancer.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "uPA is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "uPA is involved in extracellular matrix degradation, facilitating cancer invasion and metastasis.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "uPAR is glycosylated; glycosylation may modulate receptor function.", "mechanism": "uPAR binds uPA, promoting cell migration and invasion.", "protein": "Urokinase-type plasminogen activator receptor (uPAR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Oral tongue squamous cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu (rs2227564) polymorphism in uPA gene associated with increased risk.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "causal", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Gastric cancer (invasive phenotype)", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu (rs2227564) polymorphism associated with invasive phenotype.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "causal", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu (rs2227564) polymorphism not associated with ovarian cancer risk.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "no association", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu (rs2227564) polymorphism not associated with colorectal cancer risk.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "no association", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Poor coronary collateral circulation", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu T allele variant increases risk of poor collateral circulation.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "risk factor", "source_pmcid": "PMC12341408" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Not specified.", "mechanism": "Pro141Leu (rs2227564) polymorphism not associated with prostate cancer risk in Turkish population.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "no association", "source_pmcid": "PMC12341408" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "uPA is glycosylated; glycosylation may affect ELISA detection.", "mechanism": "Serum uPA levels are lower in prostate cancer patients compared to controls.", "protein": "Urokinase-type plasminogen activator (uPA)", "protein_enriched": { "function": "Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin", "gene_name": "PLAU", "glycan_count": 19, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G23626NI", "G31852PQ", "G62765YT", "G80920RR", "G82592ZH", "G86102AA", "G96881BQ", "G06330RB", "G17689DH", "G22310AV", "G37022BP", "G46665ZP", "G49108TO", "G53752TA", "G70511VE", "G84452RH", "G85194VU", "G98481KT" ], "uniprot_id": "P00749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341408" }, { "confidence": "high", "disease": "Community-acquired pneumonia", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP levels rise in response to inflammation and infection, correlating with severity and mortality risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12341414" }, { "confidence": "high", "disease": "Community-acquired pneumonia", "glycan_involvement": "Procalcitonin is glycosylated; glycosylation may influence its secretion and activity.", "mechanism": "PCT increases early in bacterial infection, serving as a marker for prognosis and severity.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12341414" }, { "confidence": "high", "disease": "Community-acquired pneumonia", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect its transport and antioxidant properties.", "mechanism": "Hypoalbuminemia is an independent risk factor for poor prognosis and mortality; albumin has antioxidant and immunomodulatory roles.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates CRP's immune functions.", "mechanism": "Elevated CRP is associated with sepsis development and progression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may influence albumin's protective effects.", "mechanism": "Low albumin accelerates sepsis; albumin supports vascular integrity and immune response.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Glycosylation affects albumin's transport and binding functions.", "mechanism": "Hypoalbuminemia increases risk and severity of bacteremia.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Cancer (lung)", "glycan_involvement": "Glycosylation may affect CRP's stability and detection.", "mechanism": "CRP is used in prognostic indices for high-mortality lung diseases.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Cancer (lung)", "glycan_involvement": "Glycosylation influences albumin's antioxidant and transport functions.", "mechanism": "Low albumin predicts poor outcomes in lung cancer and other critical illnesses.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Critical illness", "glycan_involvement": "Glycosylation modulates CRP's immune activity.", "mechanism": "CRP levels reflect inflammation and are used to assess severity in critical illness.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12341414" }, { "confidence": "medium", "disease": "Critical illness", "glycan_involvement": "Glycosylation affects albumin's binding and transport properties.", "mechanism": "Albumin maintains osmotic pressure and binds toxins; low levels worsen outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12341414" }, { "confidence": "high", "disease": "Hyperemesis gravidarum", "glycan_involvement": "BNP is N-glycosylated, which affects its stability and secretion.", "mechanism": "Elevated BNP reflects cardiac stress due to hypovolemia in HG.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation modulates BNP's plasma half-life.", "mechanism": "BNP is released in response to ventricular load and myocardial stretch.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation may influence BNP's diagnostic accuracy.", "mechanism": "BNP levels are elevated in preeclampsia, reflecting cardiac strain.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Acute coronary syndrome", "glycan_involvement": "N-glycosylation affects BNP secretion.", "mechanism": "BNP increases in response to acute cardiac stress.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Pulmonary hypertension", "glycan_involvement": "Glycosylation impacts BNP's circulatory stability.", "mechanism": "BNP rises with increased right ventricular load.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Chronic hypertension", "glycan_involvement": "N-glycosylation modulates BNP's activity.", "mechanism": "BNP reflects chronic ventricular stress.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Chronic kidney failure", "glycan_involvement": "Glycosylation may affect renal handling of BNP.", "mechanism": "BNP accumulates due to reduced renal clearance.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Hyperemesis gravidarum", "glycan_involvement": "N-glycosylation required for GDF-15 secretion and activity.", "mechanism": "GDF-15 produced by trophoblasts activates vomiting center, contributing to HG.", "protein": "Growth differentiation factor 15 (GDF-15)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Cardiac stress", "glycan_involvement": "Glycosylation influences GDF-15 stability.", "mechanism": "GDF-15 is upregulated in response to cardiac overload.", "protein": "Growth differentiation factor 15 (GDF-15)", "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "medium", "disease": "Hyperemesis gravidarum", "glycan_involvement": "ADAMTS-1 is a glycoprotein; glycosylation affects its protease activity.", "mechanism": "Elevated ADAMTS-1 reflects placental and inflammatory involvement in HG.", "protein": "ADAMTS-1", "protein_enriched": { "function": "Metalloprotease which cleaves aggrecan, a cartilage proteoglycan, at the '1938-Glu-|-Leu-1939' site (within the chondroitin sulfate attachment domain), and may be involved in its turnover (By similari", "gene_name": "ADAMTS1", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G62765YT", "G49108TO" ], "uniprot_id": "Q9UHI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341419" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "IgG glycosylation affects Fc receptor binding and anti-inflammatory activity.", "mechanism": "IVIG therapy modulates immune response and reduces autoimmune demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341533" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "High-dose IVIG glycosylation may alter viscosity and immune complex formation.", "mechanism": "IVIG administration increases risk of VTE in CIDP patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341533" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "Albumin glycosylation status may affect CSF protein levels.", "mechanism": "Albuminocytologic dissociation in CSF is diagnostic for CIDP.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "ANA glycosylation influences antigen recognition.", "mechanism": "ANA presence is used to rule out other autoimmune diseases in CIDP differential diagnosis.", "protein": "Anti-neutrophil antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylation modulates antibody specificity.", "mechanism": "Anti-RNP used in differential diagnosis for CIDP.", "protein": "Anti-ribonucleoprotein antibody (anti-RNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "CRP glycosylation affects its inflammatory activity.", "mechanism": "CRP levels monitored for inflammation in pregnancy complications.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "medium", "disease": "HELLP syndrome", "glycan_involvement": "LDH glycosylation may affect serum stability.", "mechanism": "Elevated LDH is a marker of hemolysis in HELLP syndrome.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "medium", "disease": "HELLP syndrome", "glycan_involvement": "IgG glycosylation modulates anti-inflammatory effects.", "mechanism": "IVIG may slow progression of HELLP syndrome via immunomodulation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341533" }, { "confidence": "low", "disease": "Autoimmune disorders", "glycan_involvement": "Antibody glycosylation affects antigen binding.", "mechanism": "Used to exclude other autoimmune diseases in CIDP diagnosis.", "protein": "Anti-Smith antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "low", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylation modulates antibody function.", "mechanism": "Used in differential diagnosis for CIDP.", "protein": "Anti-Ro antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12341533" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "IL-6 is a glycosylated cytokine; glycosylation affects secretion and stability.", "mechanism": "IL-6 drives inflammation and chondrocyte senescence via JAK2/STAT1 signaling.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and bioactivity.", "mechanism": "TNF-\u03b1 promotes inflammatory cascades and cartilage degradation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "IL-1\u03b2 glycosylation influences secretion and activity.", "mechanism": "IL-1\u03b2 induces matrix degradation and chondrocyte apoptosis.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Synovial inflammation", "glycan_involvement": "CD86 is heavily glycosylated; glycosylation regulates immune interactions.", "mechanism": "CD86 marks M1 pro-inflammatory macrophages driving synovial inflammation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Synovial inflammation", "glycan_involvement": "CD206 is a mannose receptor; glycosylation is essential for ligand binding.", "mechanism": "CD206 marks M2 anti-inflammatory macrophages, promoting resolution of inflammation.", "protein": "CD206", "relationship_type": "protective", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Cartilage degeneration", "glycan_involvement": "MMPs are glycosylated; glycosylation affects secretion and substrate specificity.", "mechanism": "MMPs degrade extracellular matrix, leading to cartilage loss.", "protein": "MMPs", "relationship_type": "causal", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Cartilage degeneration", "glycan_involvement": "Aggrecan is a proteoglycan with extensive glycosylation; glycan chains are critical for function.", "mechanism": "Aggrecan maintains cartilage structure; its loss accelerates degeneration.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "protective", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "Cartilage degeneration", "glycan_involvement": "Collagen II is glycosylated; glycosylation affects fibril formation and stability.", "mechanism": "Collagen II provides tensile strength to cartilage; degradation leads to OA.", "protein": "Collagen II", "relationship_type": "protective", "source_pmcid": "PMC12341631" }, { "confidence": "medium", "disease": "Synovial inflammation", "glycan_involvement": "Arginase-1 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Arginase-1 marks M2 macrophages, contributing to anti-inflammatory effects.", "protein": "Arginase-1", "relationship_type": "protective", "source_pmcid": "PMC12341631" }, { "confidence": "medium", "disease": "Synovial inflammation", "glycan_involvement": "iNOS is glycosylated; glycosylation may regulate localization and activity.", "mechanism": "iNOS marks M1 macrophages, producing NO and driving inflammation.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC12341631" }, { "confidence": "high", "disease": "SCI-induced Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Sclerostin inhibits Wnt signaling via LRP5/6, leading to reduced bone formation after SCI.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "causal", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation affects stability and extracellular activity.", "mechanism": "DKK1 upregulation inhibits Wnt/\u03b2-catenin signaling, impeding neural repair and functional recovery post-SCI.", "protein": "DKK1", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:220", "gene_name": "DKK1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "O94907" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Wnt1 activation promotes ependymal cell proliferation and spinal cord repair.", "protein": "Wnt1", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (PubMe", "gene_name": "WNT1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P04628" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Wnt3a enhances autophagy, suppresses neuronal apoptosis, and promotes axonal regeneration.", "protein": "Wnt3a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/L", "gene_name": "WNT3A", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G85146YR", "G32577BC" ], "uniprot_id": "P56704" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Axonal Degeneration", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Wnt5a overexpression impairs axonal regeneration and functional recovery after SCI.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12341850" }, { "confidence": "medium", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation affects membrane localization and ligand binding.", "mechanism": "Frizzled 5 is upregulated in reactive microglia/macrophages post-SCI, indicating Wnt pathway activation.", "protein": "Frizzled 5", "relationship_type": "biomarker", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Spinal Cord Injury", "glycan_involvement": "N-glycosylation essential for cell surface expression and Wnt binding.", "mechanism": "LRP6 expression changes post-SCI, mediating Wnt/\u03b2-catenin signaling for neural repair.", "protein": "LRP6", "protein_enriched": { "function": "Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (PubMed:11357136, PubMed:1144", "gene_name": "LRP6", "glycan_count": 4, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G81315DD", "G62765YT", "G09724ZC", "G22573RC" ], "uniprot_id": "O75581" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Axonal Degeneration", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "Ryk activation by Wnt5a inhibits corticospinal axon growth and regeneration after SCI.", "protein": "Ryk", "protein_enriched": { "function": "May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In res", "gene_name": "RYK", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G83460ZZ", "G90659AW" ], "uniprot_id": "P34925" }, "relationship_type": "causal", "source_pmcid": "PMC12341850" }, { "confidence": "medium", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Netrin-1 activates Wnt signaling, promoting neuroprotection and axonal regeneration post-SCI.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "protective", "source_pmcid": "PMC12341850" }, { "confidence": "medium", "disease": "Spinal Cord Injury", "glycan_involvement": "Glycosylation affects extracellular stability and Wnt binding.", "mechanism": "Wif1 upregulation inhibits Wnt/\u03b2-catenin signaling, limiting neural repair after SCI.", "protein": "Wif1", "protein_enriched": { "function": "Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation", "gene_name": "WIF1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9Y5W5" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12341850" }, { "confidence": "high", "disease": "Meniere\u2019s Disease", "glycan_involvement": "HSP70 is glycosylated, which may affect its immunogenicity and antibody recognition.", "mechanism": "HSP70 antibodies are elevated in MD, especially bilateral cases, suggesting an autoinflammatory mechanism.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Autoimmune Hearing Loss", "glycan_involvement": "Glycosylation may modulate HSP70\u2019s immune interactions.", "mechanism": "Autoantibodies to HSP70 are linked to autoimmune-mediated hearing loss.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "HSP70 autoantibodies are found in RA, indicating immune activation.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Celiac Disease", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "HSP70 autoantibodies are present in celiac disease.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Juvenile Idiopathic Arthritis", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "HSP70 autoantibodies are associated with JIA.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Autoimmune Liver Disease", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "HSP70 autoantibodies are linked to autoimmune liver disease.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "low", "disease": "Meniere\u2019s Disease", "glycan_involvement": "Glycosylation may affect therapeutic targeting.", "mechanism": "Potential for targeting HSP70 or its antibodies in immunomodulatory therapy for MD.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342110" }, { "confidence": "high", "disease": "Systemic Sclerosis (Scleroderma)", "glycan_involvement": "Topoisomerase I is glycosylated, which may affect autoantibody binding.", "mechanism": "SCL-70 antibodies are diagnostic for scleroderma.", "protein": "Scleroderma Antibody-70 (SCL-70, Topoisomerase I)", "protein_enriched": { "function": "Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken", "gene_name": "TOP2A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G12272NS", "G10486CT" ], "uniprot_id": "P11388" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "low", "disease": "Meniere\u2019s Disease", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Presence of SCL-70 antibodies in MD patient suggests autoimmune overlap.", "protein": "Scleroderma Antibody-70 (SCL-70, Topoisomerase I)", "protein_enriched": { "function": "Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken", "gene_name": "TOP2A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G12272NS", "G10486CT" ], "uniprot_id": "P11388" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342110" }, { "confidence": "medium", "disease": "Meniere\u2019s Disease", "glycan_involvement": "Glycosylation may modulate HSP70\u2019s immunogenicity and role in disease.", "mechanism": "Inner ear inflammation and hydrops may trigger HSP70 antibody production, contributing to MD pathogenesis.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12342110" }, { "confidence": "high", "disease": "Von Willebrand disease type 1", "glycan_involvement": "VWF is heavily glycosylated; glycosylation affects its stability and function.", "mechanism": "Quantitative deficiency of VWF leads to impaired platelet adhesion and mucocutaneous bleeding.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Protein S deficiency", "glycan_involvement": "Protein S is glycosylated; glycosylation may affect secretion and function.", "mechanism": "Reduced levels of Protein S impair anticoagulant activity, increasing risk of thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12342695" }, { "confidence": "medium", "disease": "Acute myocardial infarction (AMI)", "glycan_involvement": "Glycosylation modulates VWF interaction with platelets and endothelium.", "mechanism": "Low VWF levels may contribute to bleeding risk during AMI management.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Acute myocardial infarction (AMI)", "glycan_involvement": "Glycosylation may affect Protein S stability and anticoagulant function.", "mechanism": "Protein S deficiency increases risk of arterial thrombosis, including AMI, especially in hypercoagulable states.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Von Willebrand disease type 1", "glycan_involvement": "Factor VIII is glycosylated; glycosylation affects its plasma half-life.", "mechanism": "VWF stabilizes Factor VIII; VWF deficiency leads to secondary reduction in Factor VIII.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Mucocutaneous bleeding", "glycan_involvement": "Glycosylation is critical for VWF multimerization and function.", "mechanism": "Deficiency impairs platelet adhesion at sites of vascular injury, causing bleeding.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12342695" }, { "confidence": "medium", "disease": "Platelet dysfunction", "glycan_involvement": "Glycosylation affects receptor conformation and ligand binding.", "mechanism": "Inhibition (e.g., tirofiban) blocks platelet aggregation, used in PCI for AMI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Platelet dysfunction", "glycan_involvement": "Glycosylation modulates VWF-platelet interactions.", "mechanism": "VWF deficiency leads to impaired platelet aggregation and function.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12342695" }, { "confidence": "medium", "disease": "Mucocutaneous bleeding", "glycan_involvement": "Glycosylation may influence Protein S activity.", "mechanism": "Normal Protein S levels protect against thrombosis; deficiency may unmask bleeding disorders when anticoagulation is used.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12342695" }, { "confidence": "medium", "disease": "Protein S deficiency", "glycan_involvement": "Glycosylation of both proteins influences their plasma levels and interactions.", "mechanism": "Combined deficiency may synergistically affect hemostatic balance, increasing risk of both thrombosis and bleeding.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12342695" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22 glycoprotein 1 affects its antigenicity and immune recognition.", "mechanism": "Autoantibodies against \u03b22 glycoprotein 1 are diagnostic for APS and contribute to thrombosis.", "protein": "\u03b22 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12342896" }, { "confidence": "medium", "disease": "Adrenal infarction (AI)", "glycan_involvement": "Glycosylation modulates \u03b22 glycoprotein 1's interaction with phospholipids and immune system.", "mechanism": "APS, mediated by anti-\u03b22 glycoprotein 1 antibodies, can cause adrenal infarction via thrombosis.", "protein": "\u03b22 glycoprotein 1", "relationship_type": "causal", "source_pmcid": "PMC12342896" }, { "confidence": "high", "disease": "Molluscum contagiosum", "glycan_involvement": "Envelope glycoprotein mediates host interaction; glycosylation status may affect immune evasion and viral spread.", "mechanism": "MC021L glycoprotein is essential for viral envelope formation, egress, and cell-to-cell transmission, enabling MCV infection of keratinocytes.", "protein": "MC021L-encoded glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12343169" }, { "confidence": "high", "disease": "Molluscum contagiosum", "glycan_involvement": "Glycoprotein sequence variation (missense mutations) may alter glycan-mediated host recognition.", "mechanism": "MC021L gene detection by PCR is used for molecular diagnosis and genotyping of MCV strains.", "protein": "MC021L-encoded glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12343169" }, { "confidence": "medium", "disease": "Molluscum contagiosum", "glycan_involvement": "Altered glycosylation or amino acid changes may affect drug binding and efficacy.", "mechanism": "MC021L glycoprotein is a potential target for antipoxviral drugs due to its role in viral spread.", "protein": "MC021L-encoded glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343169" }, { "confidence": "medium", "disease": "Molluscum contagiosum", "glycan_involvement": "Amino acid changes may alter glycan structures, affecting immune recognition.", "mechanism": "Missense mutations in MC021L glycoprotein may confer viral adaptation and immune evasion, potentially impacting disease severity and transmission.", "protein": "MC021L-encoded glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12343169" }, { "confidence": "medium", "disease": "Molluscum contagiosum", "glycan_involvement": "F13L is a nonglycosylated envelope protein; MC021L glycoprotein may differ in glycosylation, impacting function.", "mechanism": "VACV F13L is homologous to MC021L; its deletion abolishes enveloped virion formation and transmission, suggesting similar function for MC021L in MCV.", "protein": "Vaccinia virus F13L (p37)", "protein_enriched": { "function": "Major component of the virion core that undergoes proteolytic processing during the immature virion (IV) to mature virion (MV) transition. Essential for the formation of a structurally normal core", "gene_name": "OPG129", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20643" }, "relationship_type": "reference/causal", "source_pmcid": "PMC12343169" }, { "confidence": "high", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "N-glycosylation critical for CER stability and secretion; altered glycosylation may affect biomarker reliability.", "mechanism": "Bidirectional serum CER fluctuations reflect hepatic synthetic reserve; decline signals progression to advanced fibrosis/cirrhosis.", "protein": "Ceruloplasmin (CER)", "relationship_type": "biomarker", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "Glycosylation affects Apo-A1 stability and function; altered glycosylation may impact hepatic fibrosis progression.", "mechanism": "Reduced Apo-A1 synthesis and increased consumption due to collagen deposition in hepatic sinusoids; early decline signals fibrosis.", "protein": "Apolipoprotein A1 (Apo-A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "LN is a heavily glycosylated ECM protein; glycosylation essential for its structural and signaling roles in fibrosis.", "mechanism": "LN upregulation by activated hepatic stellate cells drives basement membrane thickening, sinusoidal capillarization, and ECM remodeling.", "protein": "Laminin (LN)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "medium", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIb, GPIIb/IIIa) mediate adhesion and signaling; altered glycosylation may affect antifibrotic functions.", "mechanism": "PLT depletion and dysfunction (due to LN-mediated hypersplenism and copper toxicity) exacerbate ECM deposition and impair hepatic regeneration.", "protein": "Platelet (PLT)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "medium", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "HDL particles contain glycoproteins (e.g., Apo-A1); glycosylation modulates lipid transport and anti-inflammatory properties.", "mechanism": "Copper-induced mitochondrial dysfunction and lipid dysregulation lower HDL-C, promoting inflammation and fibrosis.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "medium", "disease": "Advanced hepatic fibrosis", "glycan_involvement": "TG metabolism is regulated by glycoproteins in lipoprotein complexes; glycosylation affects lipid transport and metabolism.", "mechanism": "Copper-lipid co-toxicity increases TG, driving insulin resistance, inflammation, and hepatic steatosis, accelerating fibrosis.", "protein": "Triglycerides (TG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "Wilson\u2019s disease (WD)", "glycan_involvement": "N-glycosylation required for CER secretion; defective glycosylation may further reduce CER levels.", "mechanism": "Low serum CER is a diagnostic hallmark of WD due to impaired hepatic synthesis.", "protein": "Ceruloplasmin (CER)", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "LN glycosylation critical for ECM assembly and cell signaling in cirrhotic remodeling.", "mechanism": "LN accumulation in ECM marks transition from fibrosis to cirrhosis; promotes sinusoidal capillarization and portal hypertension.", "protein": "Laminin (LN)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation affects Apo-A1 stability and hepatic export; altered glycosylation may worsen decline.", "mechanism": "Apo-A1 levels drop >70% in decompensated cirrhosis due to hepatocyte dysfunction and ECM entrapment.", "protein": "Apolipoprotein A1 (Apo-A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12343619" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "LN glycosylation modulates cell adhesion and migration, facilitating tumor microenvironment formation.", "mechanism": "LN-driven ECM remodeling and fibrosis increase risk for HCC development in advanced WD.", "protein": "Laminin (LN)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343619" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "TNF-\u03b1 is glycosylated, which may affect receptor binding and stability.", "mechanism": "Drives hepatic inflammation, insulin resistance, and progression to MASH and HCC; anti-TNF agents show therapeutic promise.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "FasL glycosylation modulates apoptotic signaling.", "mechanism": "Upregulated in MASH, promotes hepatocyte apoptosis; elevated serum levels predict NASH.", "protein": "Fas Ligand (FasL)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-m", "gene_name": "FASLG", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48023" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and receptor interaction.", "mechanism": "Promotes hepatic lipogenesis and fibrogenesis via NLRP3 inflammasome; IL-1R antagonists are therapeutic candidates.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "IL-17 glycosylation may influence receptor binding.", "mechanism": "Exacerbates hepatic inflammation and fibrosis; anti-IL-17 therapies may reduce progression.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "IL-22 glycosylation is important for stability and activity.", "mechanism": "Reduces hepatic steatosis and fibrosis, inactivates NLRP3 inflammasome; recombinant IL-22 shows benefit.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "IL-32 glycosylation may affect secretion.", "mechanism": "Upregulated in NAFLD, promotes hepatic insulin resistance; correlates with disease severity.", "protein": "IL-32", "protein_enriched": { "function": "Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis (By similarity)", "gene_name": "WDR55", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H6Y2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12343754" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "IL-34 glycosylation may modulate receptor binding.", "mechanism": "Secreted by hepatic stellate cells, increases with fibrosis progression; part of non-invasive fibrosis index.", "protein": "IL-34", "protein_enriched": { "function": "Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate ", "gene_name": "IL34", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G80920RR" ], "uniprot_id": "Q6ZMJ4" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "CCL2 glycosylation affects chemotactic activity.", "mechanism": "Promotes monocyte recruitment, hepatic inflammation, and fibrosis; CCR2 inhibitors improve NASH.", "protein": "MCP-1 (CCL2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "CXCL8 glycosylation modulates receptor interaction.", "mechanism": "Elevated in NASH, drives neutrophil recruitment and fibrosis; included in diagnostic scores.", "protein": "CXCL8 (IL-8)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343754" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "RANKL glycosylation affects receptor binding and function.", "mechanism": "Promotes hepatic macrophage infiltration and steatosis; anti-RANKL therapy under investigation.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343754" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "N-glycosylation profile altered; used for diagnosis.", "mechanism": "Underglycosylation of transferrin reflects defective N-glycosylation in PMM2-CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "ALG13-CDG", "glycan_involvement": "N-glycosylation affects receptor expression and function.", "mechanism": "Reduced abundance of PDGFR\u03b2 impairs AAV5 entry in ALG13-CDG.", "protein": "PDGFR\u03b2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic ", "gene_name": "PDGFRB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G48414YA", "G38663NM", "G52131KU", "G86500WE", "G49108TO" ], "uniprot_id": "P09619" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "Impaired N-glycan processing in Golgi; affects terminal galactose and sialic acid.", "mechanism": "PGM1 deficiency disrupts UDP-galactose metabolism, causing mixed glycosylation defects.", "protein": "PGM1", "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Impaired early N-glycan assembly in ER.", "mechanism": "PMM2 mutations cause defective N-glycosylation, leading to multisystem disease.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "ALG13-CDG", "glycan_involvement": "Defective N-glycosylation initiation.", "mechanism": "ALG13 mutations disrupt ER glycosylation, causing neurological symptoms.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Reduced galactosylation and glycan complexity on receptor.", "mechanism": "Altered glycosylation may reduce AAV8/9 binding via laminin receptor in Alzheimer's disease.", "protein": "Laminin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "COG7-CDG", "glycan_involvement": "Defective N-glycan maturation in Golgi.", "mechanism": "COG7 mutations impair Golgi glycosylation, causing CDG.", "protein": "COG7", "protein_enriched": { "function": "Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chroma", "gene_name": "STAG1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59626AS", "G49108TO" ], "uniprot_id": "Q8WVM7" }, "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "medium", "disease": "CDG", "glycan_involvement": "Impaired glycosyltransferase activity.", "mechanism": "EXT1 mutations affect glycosaminoglycan synthesis, contributing to CDG.", "protein": "EXT1", "protein_enriched": { "function": "The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or ", "gene_name": "TAF6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P49848" }, "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "medium", "disease": "CDG", "glycan_involvement": "Defective GPI-anchor glycosylation.", "mechanism": "PGAP2 mutations disrupt GPI-anchor biosynthesis, causing glycosylation defects.", "protein": "PGAP2", "relationship_type": "causal", "source_pmcid": "PMC12343853" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Reduced galactosylation, fucosylation, and glycan complexity.", "mechanism": "Altered glycosylation of transferrin observed in Alzheimer's disease brain tissue.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343853" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Core fucosylation of N-glycans on LMWK modulates its function in fibrosis.", "mechanism": "Elevated LMWK-Fc levels correlate with liver fibrosis severity; reflects activation of hepatic stellate cells and fibrogenesis.", "protein": "Core-fucosylated low-molecular-weight kininogen (LMWK-Fc)", "relationship_type": "biomarker", "source_pmcid": "PMC12344353" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Core fucosylation increases in cirrhosis, reflecting disease progression.", "mechanism": "LMWK-Fc levels are significantly elevated in cirrhosis, indicating advanced fibrosis.", "protein": "Core-fucosylated low-molecular-weight kininogen (LMWK-Fc)", "relationship_type": "biomarker", "source_pmcid": "PMC12344353" }, { "confidence": "medium", "disease": "Pulmonary interstitial fibrosis", "glycan_involvement": "Altered core fucosylation associated with fibrotic tissue remodeling.", "mechanism": "LMWK-Fc levels are closely related to pulmonary fibrosis, suggesting a role in fibrotic processes.", "protein": "Core-fucosylated low-molecular-weight kininogen (LMWK-Fc)", "relationship_type": "biomarker", "source_pmcid": "PMC12344353" }, { "confidence": "medium", "disease": "Renal interstitial fibrosis", "glycan_involvement": "Core fucosylation modulates LMWK function in renal fibrosis.", "mechanism": "LMWK-Fc levels correlate with renal fibrosis, indicating involvement in fibrogenesis.", "protein": "Core-fucosylated low-molecular-weight kininogen (LMWK-Fc)", "relationship_type": "biomarker", "source_pmcid": "PMC12344353" }, { "confidence": "high", "disease": "Vascular Intimal Hyperplasia", "glycan_involvement": "ICAM-1 is a glycoprotein; glycosylation is essential for its cell surface localization and function.", "mechanism": "MPs stimulate ICAM-1 production in smooth muscle cells, promoting inflammation and cell adhesion.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12344357" }, { "confidence": "high", "disease": "Vascular Intimal Hyperplasia", "glycan_involvement": "VCAM-1 is a glycoprotein; glycosylation is required for its adhesive function.", "mechanism": "MPs increase VCAM-1 levels, enhancing inflammatory response and cell adhesion in vascular tissue.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "Coronary Atherosclerotic Heart Disease", "glycan_involvement": "Glycosylation modulates ICAM-1's interaction with leukocytes.", "mechanism": "Elevated ICAM-1 indicates vascular inflammation and poor prognosis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "Coronary Atherosclerotic Heart Disease", "glycan_involvement": "Glycosylation is critical for VCAM-1's binding to integrins.", "mechanism": "VCAM-1 upregulation marks vascular inflammation and adverse outcomes.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "In-Stent Restenosis", "glycan_involvement": "Glycosylation affects ICAM-1's stability and immune interactions.", "mechanism": "Inhibition or deletion of ICAM-1 reduces inflammation and restenosis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "In-Stent Restenosis", "glycan_involvement": "Glycosylation required for VCAM-1's cell adhesion properties.", "mechanism": "VCAM-1 levels correlate with restenosis severity.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344357" }, { "confidence": "high", "disease": "Vascular Intimal Hyperplasia", "glycan_involvement": "MPs carry glycoproteins including ICAM-1/VCAM-1, facilitating cell-cell interactions.", "mechanism": "MPs from patients stimulate smooth muscle cell proliferation and migration via ERK and P38 pathways.", "protein": "Microparticles (EMPs, PMPs)", "relationship_type": "causal", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "Acute Coronary Syndrome", "glycan_involvement": "Glycoprotein content of MPs influences their biological activity.", "mechanism": "MPs impair vascular function by modulating eNOS and oxidative stress.", "protein": "Microparticles (EMPs, PMPs)", "relationship_type": "causal", "source_pmcid": "PMC12344357" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycoproteins on MPs mediate endothelial interactions.", "mechanism": "MPs disrupt NO/O2- balance, exacerbating vascular injury.", "protein": "Microparticles (EMPs, PMPs)", "relationship_type": "causal", "source_pmcid": "PMC12344357" }, { "confidence": "low", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycosylation regulates ICAM-1's immune cell binding.", "mechanism": "ICAM-1 upregulation reflects inflammatory status post-infarction.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344357" }, { "confidence": "high", "disease": "Congenital cytomegalovirus (CMV) infection", "glycan_involvement": "Glycosylation of viral envelope proteins is essential for infectivity and immune modulation.", "mechanism": "Viral glycoproteins mediate host cell entry and immune evasion, leading to systemic infection.", "protein": "Cytomegalovirus glycoproteins (e.g., gB, gH/gL complexes)", "relationship_type": "causal", "source_pmcid": "PMC12344389" }, { "confidence": "high", "disease": "CMV pneumonitis", "glycan_involvement": "Glycans on viral proteins interact with host cell receptors in the lung.", "mechanism": "Viral glycoproteins facilitate infection of lung tissue, causing inflammation and pneumonitis.", "protein": "Cytomegalovirus glycoproteins (e.g., gB, gH/gL complexes)", "relationship_type": "causal", "source_pmcid": "PMC12344389" }, { "confidence": "medium", "disease": "Childhood interstitial lung disease (chILD)", "glycan_involvement": "N-glycosylation is required for proper folding and function.", "mechanism": "Mutations in SFTPB can cause surfactant dysfunction, leading to ILD.", "protein": "Surfactant protein B (SFTPB)", "protein_enriched": { "function": "Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of pa", "gene_name": "SFTPB", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07988" }, "relationship_type": "causal (genetic forms)", "source_pmcid": "PMC12344389" }, { "confidence": "medium", "disease": "Childhood interstitial lung disease (chILD)", "glycan_involvement": "Glycosylation affects protein stability and trafficking.", "mechanism": "SFTPC mutations disrupt surfactant homeostasis, causing ILD.", "protein": "Surfactant protein C (SFTPC)", "protein_enriched": { "function": "Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces", "gene_name": "SFTPC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11686" }, "relationship_type": "causal (genetic forms)", "source_pmcid": "PMC12344389" }, { "confidence": "medium", "disease": "Childhood interstitial lung disease (chILD)", "glycan_involvement": "N-glycosylation modulates immune recognition and surfactant activity.", "mechanism": "SFTPA mutations impair innate immunity and surfactant function, contributing to ILD.", "protein": "Surfactant protein A (SFTPA1/2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (genetic forms)", "source_pmcid": "PMC12344389" }, { "confidence": "high", "disease": "Congenital cytomegalovirus (CMV) infection", "glycan_involvement": "Fc glycosylation affects antibody effector function.", "mechanism": "Maternal and neonatal IgG used for serological diagnosis of CMV infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12344389" }, { "confidence": "high", "disease": "Congenital cytomegalovirus (CMV) infection", "glycan_involvement": "Glycosylation influences IgM structure and detection.", "mechanism": "Neonatal IgM indicates recent or congenital infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344389" }, { "confidence": "low", "disease": "Persistent pulmonary hypertension of the newborn (PPHN)", "glycan_involvement": "N-glycosylation required for surfactant activity.", "mechanism": "SFTPB deficiency can contribute to impaired lung function and PPHN.", "protein": "Surfactant protein B (SFTPB)", "protein_enriched": { "function": "Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of pa", "gene_name": "SFTPB", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07988" }, "relationship_type": "causal (rare genetic forms)", "source_pmcid": "PMC12344389" }, { "confidence": "medium", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Glycosylation enables neurotropism and immune evasion.", "mechanism": "CMV infection of neural tissues mediated by viral glycoproteins leads to SNHL.", "protein": "Cytomegalovirus glycoproteins (e.g., gB, gH/gL complexes)", "relationship_type": "causal", "source_pmcid": "PMC12344389" }, { "confidence": "low", "disease": "Persistent pulmonary hypertension of the newborn (PPHN)", "glycan_involvement": "Glycosylation affects protein processing.", "mechanism": "SFTPC dysfunction may contribute to abnormal lung development and PPHN.", "protein": "Surfactant protein C (SFTPC)", "protein_enriched": { "function": "Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces", "gene_name": "SFTPC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11686" }, "relationship_type": "causal (rare genetic forms)", "source_pmcid": "PMC12344389" }, { "confidence": "high", "disease": "Metastatic Uveal Melanoma (mUM)", "glycan_involvement": "gp100 is a glycoprotein; glycosylation may affect antigen processing and presentation, influencing immune recognition.", "mechanism": "gp100 peptide is targeted by tebentafusp, a bispecific T-cell engager, leading to redirected T-cell cytotoxicity against melanoma cells expressing gp100 in the context of HLA-A*02:01.", "protein": "Glycoprotein 100 (gp100)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344395" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and trafficking.", "mechanism": "APP is sequentially cleaved to produce amyloid-beta peptides, which aggregate and form plaques central to AD pathology.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycosylation required for secretion and function.", "mechanism": "YKL-40 is produced by activated astrocytes and microglia; elevated in CSF/plasma in AD, reflecting neuroinflammation.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates filament assembly and stability.", "mechanism": "GFAP is upregulated in reactive astrocytes during AD; plasma/CSF levels correlate with disease progression and A\u03b2 pathology.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "TREM2 is expressed on microglia; regulates immune response and A\u03b2 clearance. Mutations increase AD risk.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344583" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Derived from glycosylated TREM2 ectodomain.", "mechanism": "sTREM2 levels in CSF/plasma peak in MCI and decline in dementia; reflects microglial activation.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates aggregation and phosphorylation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles; CSF/plasma p-tau isoforms are diagnostic and track progression.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences lipid binding and receptor interactions.", "mechanism": "ApoE4 allele increases AD risk, affects A\u03b2 aggregation and clearance.", "protein": "ApoE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "IBA-1 marks microglial activation; increased in AD brain tissue.", "protein": "IBA-1", "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects filament assembly.", "mechanism": "Elevated NfL in CSF/plasma indicates neuroaxonal damage and correlates with AD severity.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "Glycosylation required for function.", "mechanism": "YKL-40 levels are elevated but lower than in AD; helps differential diagnosis.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12344583" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation of H is essential for receptor binding and immune evasion.", "mechanism": "H glycoprotein mediates viral attachment to host cell receptors, initiating infection.", "protein": "Measles virus hemagglutinin (H) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation modulates fusogenic activity and antigenicity.", "mechanism": "F glycoprotein facilitates fusion of viral and host membranes, enabling viral entry.", "protein": "Measles virus fusion (F) glycoprotein", "protein_enriched": { "function": "Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell", "gene_name": "Rpl34", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11250" }, "relationship_type": "causal", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "IgM is a glycoprotein; glycosylation affects stability and immune function.", "mechanism": "Measles-specific IgM is used for serologic diagnosis of acute infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "IgG glycosylation modulates effector functions and half-life.", "mechanism": "Measles-specific IgG indicates immunity and protection post-vaccination or infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation of vaccine antigens is required for immunogenicity.", "mechanism": "Vaccination induces immune response against viral glycoproteins, preventing infection.", "protein": "Measles, Mumps, Rubella vaccine glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12345067" }, { "confidence": "medium", "disease": "Measles-associated pneumonia", "glycan_involvement": "Glycosylation influences tissue tropism and immune escape.", "mechanism": "Viral entry via H glycoprotein can lead to respiratory tract infection and pneumonia.", "protein": "Measles virus hemagglutinin (H) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12345067" }, { "confidence": "medium", "disease": "Measles-associated encephalitis", "glycan_involvement": "Glycosylation may affect neurotropism.", "mechanism": "Neuroinvasion by measles virus via H glycoprotein can cause encephalitis.", "protein": "Measles virus hemagglutinin (H) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12345067" }, { "confidence": "medium", "disease": "Measles-associated thrombocytopenia", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Measles infection can trigger immune-mediated platelet destruction.", "protein": "Measles virus hemagglutinin (H) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12345067" }, { "confidence": "medium", "disease": "Measles-associated thrombocytopenia", "glycan_involvement": "Glycosylation affects IgM function in immune response.", "mechanism": "Elevated IgM may correlate with acute phase and complications.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. 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In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Measles-associated complications", "glycan_involvement": "Glycosylation is necessary for proper antigen presentation.", "mechanism": "Vaccination prevents complications by inducing immunity.", "protein": "Measles, Mumps, Rubella vaccine glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12345067" }, { "confidence": "high", "disease": "Protein S deficiency (PSD)", "glycan_involvement": "Protein S is a glycoprotein; glycosylation is essential for stability and function.", "mechanism": "Mutations in PROS1 gene reduce functional protein S, impairing anticoagulation.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation maintains protein S structure and anticoagulant activity.", "mechanism": "PSD leads to impaired inactivation of coagulation factors Va and VIIIa, increasing VTE risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation required for proper secretion and function.", "mechanism": "Reduced protein S activity due to PROS1 mutations increases DVT risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "Pulmonary embolism (PE)", "glycan_involvement": "Glycosylation affects protein S stability and plasma levels.", "mechanism": "PSD increases risk of PE by promoting thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation is necessary for anticoagulant function; deficiency may exacerbate risk.", "mechanism": "Hereditary PSD may contribute to arterial thrombosis and recurrent ischemic stroke.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation supports protein S activity in coagulation regulation.", "mechanism": "Family history suggests PSD may increase risk of arterial events like MI.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "Femoral vein thrombosis", "glycan_involvement": "Glycosylation required for functional protein S.", "mechanism": "Reduced protein S activity due to PROS1 mutation increases risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12345075" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation status may affect response to therapy.", "mechanism": "Anticoagulation (DOACs) effective in preventing recurrence in PSD-related stroke.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation influences assay sensitivity and specificity.", "mechanism": "Low protein S activity is a diagnostic biomarker for hereditary thrombophilia.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345075" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation affects plasma levels and detection.", "mechanism": "Reduced protein S activity may indicate risk for recurrent stroke in hereditary PSD.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345075" }, { "confidence": "high", "disease": "PVNS", "glycan_involvement": "CSF1 is glycosylated, which may affect secretion and receptor binding.", "mechanism": "CSF1 overexpression drives abnormal macrophage recruitment and synovial proliferation.", "protein": "CSF1", "relationship_type": "causal", "source_pmcid": "PMC12345121" }, { "confidence": "high", "disease": "PVNS", "glycan_involvement": "CSF1R glycosylation is important for cell surface expression and ligand binding.", "mechanism": "CSF1R activation by CSF1/IL-34 promotes monocyte/macrophage proliferation; inhibitors (e.g., pexidartinib) are used therapeutically.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "PVNS", "glycan_involvement": "IL-34 is glycosylated, which may influence stability and receptor interaction.", "mechanism": "IL-34 acts as an alternative ligand for CSF1R, supporting macrophage expansion in PVNS.", "protein": "IL-34", "protein_enriched": { "function": "Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate ", "gene_name": "IL34", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G80920RR" ], "uniprot_id": "Q6ZMJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "Sj\u00f6gren's Syndrome", "glycan_involvement": "Glycosylation may affect IL-34 secretion and immune recognition.", "mechanism": "IL-34 is overexpressed in inflamed salivary glands, correlating with monocyte infiltration.", "protein": "IL-34", "protein_enriched": { "function": "Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate ", "gene_name": "IL34", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G80920RR" ], "uniprot_id": "Q6ZMJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "Sj\u00f6gren's Syndrome", "glycan_involvement": "Glycosylation required for CSF1R function.", "mechanism": "CSF1R signaling implicated in monocyte/macrophage expansion in SS.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345121" }, { "confidence": "high", "disease": "PVNS", "glycan_involvement": "CD68 is heavily glycosylated, affecting its detection and function.", "mechanism": "CD68+ macrophages are abundant in PVNS lesions.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates CSF1R activity.", "mechanism": "CSF1R pathway contributes to macrophage-driven inflammation in RA.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "SLE", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "CSF1R signaling involved in monocyte/macrophage expansion in SLE.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345121" }, { "confidence": "medium", "disease": "Psoriatic Arthritis", "glycan_involvement": "Glycosylation affects receptor-ligand interactions.", "mechanism": "CSF1R pathway implicated in inflammatory cell recruitment.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345121" }, { "confidence": "high", "disease": "Sj\u00f6gren's Syndrome", "glycan_involvement": "SSA/Ro glycosylation may influence autoantigenicity.", "mechanism": "Autoantibodies against SSA/Ro are diagnostic for SS.", "protein": "SSA/Ro", "relationship_type": "biomarker", "source_pmcid": "PMC12345121" }, { "confidence": "high", "disease": "Cardiac arrest", "glycan_involvement": "Fibrinogen glycosylation affects its stability and function in coagulation.", "mechanism": "Reduced fibrinogen levels are associated with increased mortality post-resuscitation, reflecting impaired coagulation and inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. 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Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12345314" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation influences fibrinogen's inflammatory properties.", "mechanism": "Circulating fibrinogen levels correlate with outcomes in critically ill septic patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345314" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation may affect fibrinogen's role in inflammation.", "mechanism": "Fibrinogen is a prognostic biomarker for COPD severity and outcomes.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. 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Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345314" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation affects fibrinogen's renal clearance and function.", "mechanism": "Circulating fibrinogen levels are associated with outcomes in AKI.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345314" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation modulates fibrinogen's activity in thrombus formation.", "mechanism": "Fibrinogen contributes to stroke pathogenesis via coagulation and inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12345314" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation may affect fibrinogen's crossing of the blood-brain barrier.", "mechanism": "Fibrinogen implicated in neuroinflammation and vascular dysfunction in Alzheimer\u2019s.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12345314" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation influences fibrinogen's immune interactions.", "mechanism": "Fibrinogen promotes neuroinflammation and demyelination in MS.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12345314" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect membrane targeting and complex stability.", "mechanism": "Regulates insulin granule exocytosis via complex formation with LIN10 and STXBP1; loss impairs insulin secretion.", "protein": "LIN2 (CASK)", "protein_enriched": { "function": "Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion ch", "gene_name": "CASK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O14936" }, "relationship_type": "causal", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation may modulate channel interactions.", "mechanism": "Regulates CaMKII activity and sodium channel trafficking; loss leads to arrhythmias and systolic dysfunction.", "protein": "LIN2 (CASK)", "protein_enriched": { "function": "Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion ch", "gene_name": "CASK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O14936" }, "relationship_type": "causal", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Pancreatic Adenocarcinoma", "glycan_involvement": "Glycosylation may affect cell surface localization.", "mechanism": "High expression correlates with poor prognosis; promotes proliferation via Notch pathway.", "protein": "LIN2 (CASK)", "protein_enriched": { "function": "Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion ch", "gene_name": "CASK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O14936" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345355" }, { "confidence": "medium", "disease": "Cholangiocarcinoma", "glycan_involvement": "Glycosylation status may influence detection.", "mechanism": "LIN2-negative expression associated with decreased survival.", "protein": "LIN2 (CASK)", "protein_enriched": { "function": "Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion ch", "gene_name": "CASK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O14936" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation may affect PDZ domain interactions.", "mechanism": "PDZ domain targets CD98; engineered chimeras induce apoptosis in glioblastoma cells.", "protein": "LIN2 (CASK)", "protein_enriched": { "function": "Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion ch", "gene_name": "CASK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O14936" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation may influence protein stability and localization.", "mechanism": "Hypermethylation of LIN10 gene associated with CRC development and poor survival.", "protein": "LIN10 (MINT1/APBA1)", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "NDUFB8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95169" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "LIN10 methylation correlates with HCC progression and poor prognosis.", "protein": "LIN10 (MINT1/APBA1)", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "NDUFB8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95169" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation may regulate membrane localization.", "mechanism": "CASC9/miR-758-3p/LIN7A axis promotes proliferation; LIN7A overexpression accelerates tumour growth.", "protein": "LIN7A", "protein_enriched": { "function": "Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may ", "gene_name": "LIN7C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NUP9" }, "relationship_type": "causal", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may modulate receptor interactions.", "mechanism": "Overexpression disrupts polarity, activates MEK/ERK and PI3K/AKT pathways, enhances invasiveness.", "protein": "LIN7A", "protein_enriched": { "function": "Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may ", "gene_name": "LIN7C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NUP9" }, "relationship_type": "causal", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation may affect cell adhesion properties.", "mechanism": "Hypermethylation reduces expression; overexpression inhibits metastasis.", "protein": "LIN7C", "protein_enriched": { "function": "tRNA methylase which 2'-O-methylates cytidine(4) in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine(4) in tRNA(His)", "gene_name": "TRMT13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G27058EU" ], "uniprot_id": "Q9NUP7" }, "relationship_type": "protective", "source_pmcid": "PMC12345355" }, { "confidence": "high", "disease": "Endotoxemia", "glycan_involvement": "SAA is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "SAA levels increase during endotoxemia as part of the acute-phase response.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "high", "disease": "Endotoxemia", "glycan_involvement": "Haptoglobin is N-glycosylated; glycosylation modulates its anti-inflammatory function.", "mechanism": "Haptoglobin increases in plasma during endotoxemia, reflecting inflammation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "CRP is glycosylated; glycan structures influence its ligand binding.", "mechanism": "CRP is elevated in sepsis and used as a diagnostic/prognostic marker.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Presepsin is a glycoprotein; glycosylation may affect detection and clearance.", "mechanism": "Presepsin is an early marker of sepsis, rising before other acute-phase proteins.", "protein": "Presepsin", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects SAA's serum kinetics.", "mechanism": "SAA increases in sepsis, but hematologic ratios change more rapidly.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation modulates haptoglobin's anti-inflammatory properties.", "mechanism": "Haptoglobin rises in sepsis as part of the acute-phase response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Endotoxemia", "glycan_involvement": "TNF\u03b1 is glycosylated; glycosylation influences secretion and receptor binding.", "mechanism": "TNF\u03b1 increases rapidly after LPS infusion, indicating acute inflammation.", "protein": "Tumor Necrosis Factor alpha (TNF\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Endotoxemia", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects bioactivity.", "mechanism": "IL-1\u03b2 rises in plasma after LPS, reflecting inflammatory activation.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Glycosylation modulates SAA's function and clearance.", "mechanism": "SAA is elevated in SIRS, but hematologic ratios may change earlier.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "N-glycosylation affects haptoglobin's anti-inflammatory activity.", "mechanism": "Haptoglobin increases in SIRS as part of the acute-phase response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345425" }, { "confidence": "medium", "disease": "Feather dystrophy in griffon vultures", "glycan_involvement": "VP-1 is a glycoprotein; glycosylation may affect viral assembly and immune recognition.", "mechanism": "VP-1 detected in intranuclear inclusion bodies in affected feather follicles, suggesting viral replication and cytopathic effect leading to feather dystrophy.", "protein": "Avian polyomavirus VP-1", "relationship_type": "causal", "source_pmcid": "PMC12345491" }, { "confidence": "low", "disease": "Feather dystrophy in griffon vultures", "glycan_involvement": "Glycosylation of glycoprotein E is important for viral entry and immune evasion.", "mechanism": "Tested as a marker for herpesvirus involvement; negative immunohistochemistry suggests no causal role.", "protein": "ILTV glycoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12345491" }, { "confidence": "low", "disease": "Pinching Off Syndrome (POS)", "glycan_involvement": "VP-1 glycosylation may influence tissue tropism and immune response.", "mechanism": "Similar histopathological features in POS and APV infection suggest a possible link.", "protein": "Avian polyomavirus VP-1", "relationship_type": "causal", "source_pmcid": "PMC12345491" }, { "confidence": "high", "disease": "Psittacine Beak and Feather Disease (PBFD)", "glycan_involvement": "Glycosylation of VP-1 may modulate host-pathogen interactions.", "mechanism": "APV is known to cause feather dystrophy in parrots, with similar inclusion bodies and follicular necrosis.", "protein": "Avian polyomavirus VP-1", "relationship_type": "causal", "source_pmcid": "PMC12345491" }, { "confidence": "low", "disease": "Pinching Off Syndrome (POS)", "glycan_involvement": "Glycosylation affects antigenicity and immune detection.", "mechanism": "Used to rule out herpesvirus etiology in POS cases.", "protein": "ILTV glycoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12345491" }, { "confidence": "high", "disease": "Feather dystrophy in parrots", "glycan_involvement": "Glycosylation may affect viral spread and immune evasion.", "mechanism": "VP-1 is a marker of APV infection, which causes feather dystrophy via follicular necrosis.", "protein": "Avian polyomavirus VP-1", "relationship_type": "causal", "source_pmcid": "PMC12345491" }, { "confidence": "low", "disease": "Feather dystrophy in parrots", "glycan_involvement": "Glycosylation is critical for viral infectivity.", "mechanism": "Used to distinguish herpesvirus-induced feather dystrophy from APV-induced cases.", "protein": "ILTV glycoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12345491" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Sclerostin inhibits Wnt signaling, reducing bone formation and muscle function; elevated in osteoporosis.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "Muscle Atrophy", "glycan_involvement": "Glycosylation affects cell surface expression and signaling.", "mechanism": "Osteoactivin protects injured muscle from fibrosis and promotes regeneration after denervation.", "protein": "Osteoactivin", "protein_enriched": { "function": "Binds anionic lipids and gangliosides at acidic pH", "gene_name": "EPDR1", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G44753VC" ], "uniprot_id": "Q9UM22" }, "relationship_type": "protective", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation modulates stability and receptor interaction.", "mechanism": "FGF23 overexpression leads to muscle wasting, insulin resistance, and inflammation in CKD.", "protein": "FGF23", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12345649" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "\u03b3-carboxylation (not classical glycosylation) is essential for function.", "mechanism": "Osteocalcin promotes muscle glucose uptake and IL-6 production, supporting muscle metabolism.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "protective", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "Age-related Muscle Loss", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "IGF-1 stimulates muscle protein synthesis and regeneration, counteracting sarcopenia.", "protein": "IGF-1", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "Muscle Atrophy", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Myostatin inhibits muscle growth and differentiation; elevated in muscle wasting.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "Osteolytic Diseases", "glycan_involvement": "Glycosylation required for stability and secretion.", "mechanism": "IL-6 promotes bone loss and muscle protein breakdown in osteolytic conditions.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12345649" }, { "confidence": "medium", "disease": "Muscle Atrophy", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-15 stimulates myoblast development and prevents muscle protein breakdown.", "protein": "IL-15", "protein_enriched": { "function": "High-affinity receptor for interleukin-15 (PubMed:8530383). Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells (By similarity). I", "gene_name": "IL15RA", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q13261" }, "relationship_type": "protective", "source_pmcid": "PMC12345649" }, { "confidence": "medium", "disease": "Osteogenesis Imperfecta", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Irisin antagonizes TGF-\u03b2/Smad signaling, promoting osteogenesis and reducing fractures.", "protein": "Irisin (FNDC5)", "protein_enriched": { "function": "Mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA", "gene_name": "FNDC5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8NAU1" }, "relationship_type": "protective", "source_pmcid": "PMC12345649" }, { "confidence": "medium", "disease": "Bone Metastases in Breast Cancer", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "Sclerostin inhibition ameliorates bone metastases and muscle weakness in breast cancer.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12345649" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is heavily glycosylated; glycan shield modulates immune evasion and entry.", "mechanism": "Plant-derived compounds (punicalin, punicalagin, emodin, EGCG) inhibit S protein\u2013ACE2 interaction, blocking viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is highly glycosylated; glycans mediate receptor binding and shield from antibodies.", "mechanism": "Phytochemicals (baicalin) inhibit gp120 binding to CD4, blocking HIV entry.", "protein": "gp120/gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "E protein glycosylation affects receptor binding and immune recognition.", "mechanism": "Plant compounds (naringenin, baicalein, gossypol) inhibit E protein\u2013host receptor interaction, preventing viral entry.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "Zika virus disease", "glycan_involvement": "Glycosylation modulates E protein structure and host interaction.", "mechanism": "EGCG and baicalin bind ZIKV E protein, blocking entry and fusion.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA glycosylation regulates receptor binding and antigenicity.", "mechanism": "EGCG, quercetin, and catechins bind HA, blocking sialic acid-mediated entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "GP is heavily glycosylated; glycans mediate host cell binding and immune evasion.", "mechanism": "Proanthocyanidins and quercetin inhibit GP-mediated entry by blocking host receptor interaction.", "protein": "Glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Direct binding to viral glycan structures.", "mechanism": "GRFT binds high-mannose glycans on HIV envelope, neutralizing virus.", "protein": "Griffithsin (GRFT)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6Y2C6" }, "relationship_type": "protective", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Direct binding to spike glycan shield.", "mechanism": "GRFT binds glycans on SARS-CoV-2 spike, inhibiting entry.", "protein": "Griffithsin (GRFT)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6Y2C6" }, "relationship_type": "protective", "source_pmcid": "PMC12345658" }, { "confidence": "medium", "disease": "Ebola virus disease", "glycan_involvement": "N-glycosylation in ER increases antibody-virus binding efficiency.", "mechanism": "Plant-derived antibodies with high-mannose N-glycans (via KDEL motif) show enhanced binding to Ebola virus.", "protein": "Antibody Fc region", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycoengineering of N-glycans enhances effector function.", "mechanism": "Plantibodies with homogeneous GnGn N-glycans (\u0394XF plants) have increased affinity for Fc\u03b3RIIIa, improving antiviral activity.", "protein": "Antibody Fc region", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345658" }, { "confidence": "high", "disease": "Gaucher disease", "glycan_involvement": "PSAP is a glycoprotein; glycosylation is required for proper folding and function.", "mechanism": "PSAP mutations (especially affecting Sap C) reduce GCase activity, causing glucosylceramide accumulation.", "protein": "Prosaposin (PSAP)", "protein_enriched": { "function": "Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently ac", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602" }, "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "high", "disease": "Gaucher disease", "glycan_involvement": "Sap C is glycosylated; glycosylation critical for function.", "mechanism": "Sap C deficiency impairs GCase activation, leading to substrate accumulation and GD phenotype.", "protein": "Saposin C", "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "high", "disease": "Krabbe disease", "glycan_involvement": "Glycosylation status regulates Sap A\u2019s lipid extraction activity.", "mechanism": "Sap A mutations (e.g., p.I86N) disrupt galactosylceramidase activation, causing psychosine accumulation.", "protein": "Saposin A", "protein_enriched": { "function": "", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602-1" }, "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "high", "disease": "Metachromatic leukodystrophy", "glycan_involvement": "Glycosylation site mutations disrupt Sap B function.", "mechanism": "Sap B deficiency impairs arylsulfatase A activation, causing sulfatide accumulation.", "protein": "Saposin B", "protein_enriched": { "function": "", "gene_name": "PSAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07602-2" }, "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation required for PSAP secretion and function.", "mechanism": "PSAP variants and deficiency disrupt lipid homeostasis, increase \u03b1-synuclein aggregation, and impair dopaminergic neuron survival.", "protein": "Prosaposin (PSAP)", "protein_enriched": { "function": "Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently ac", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12345702" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation required for Sap C function.", "mechanism": "Reduced Sap C impairs GCase activity, promoting \u03b1-synuclein aggregation.", "protein": "Saposin C", "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation required for PSAP function.", "mechanism": "PSAP interacts with PGRN; dysfunction leads to saposin accumulation in neurites and worsens AD pathology.", "protein": "Prosaposin (PSAP)", "protein_enriched": { "function": "Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently ac", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602" }, "relationship_type": "causal", "source_pmcid": "PMC12345702" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified, but PSAP glycosylation may affect immune signaling.", "mechanism": "PSAP modulates macrophage function and inflammation, influencing plaque formation.", "protein": "Prosaposin (PSAP)", "protein_enriched": { "function": "Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently ac", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12345702" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "TGF-\u03b2-induced over-glycosylation of PSAP impairs lysosomal antigen processing.", "mechanism": "PSAP promotes or inhibits tumor growth (context-dependent); over-glycosylation impairs antigen processing in tumor microenvironment.", "protein": "Prosaposin (PSAP)", "protein_enriched": { "function": "Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently ac", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", 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"high", "disease": "Porcine epidemic diarrhea (PED)", "glycan_involvement": "D0 domain mediates sialic acid binding, a glycan-dependent interaction affecting pathogenicity.", "mechanism": "Mutations at D0 domain residues 113/114 (HN\u2192IG) in S protein are linked to increased virulence in clade 2 S-INDEL strains.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "virulence determinant", "source_pmcid": "PMC12345761" }, { "confidence": "medium", "disease": "Porcine epidemic diarrhea (PED)", "glycan_involvement": "Mutations may alter glycosylation patterns, affecting antigenicity and immune recognition.", "mechanism": "Clade-specific amino acid changes in S protein (especially in D0 and NTD domains) distinguish virulent lineages.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, 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"mechanism": "Recombination events in S gene generate novel S-INDEL lineages with altered virulence and transmission.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12345761" }, { "confidence": "medium", "disease": "Porcine epidemic diarrhea (PED)", "glycan_involvement": "Selected sites may overlap with glycosylation motifs, influencing immune escape.", "mechanism": "Positive selection at S protein codons (e.g., 83, 113, 114, 156, 309, 609) marks adaptive evolution in virulent strains.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12345761" }, { "confidence": "high", "disease": "Porcine epidemic 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Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345908" }, { "confidence": "medium", "disease": "Acetabular Labrum Degeneration", "glycan_involvement": "N-glycosylation affects CD31 function in angiogenesis.", "mechanism": "Increased CD31+ endothelial cells indicate pathological neovascularization.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12345908" }, { "confidence": "medium", "disease": "Hip Osteoarthritis", "glycan_involvement": "Therapeutic efficacy depends on proper O-glycosylation.", "mechanism": "Restoration of Lubricin may improve lubrication and slow degeneration.", "protein": "Lubricin", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "PRG4", "glycan_count": 23, "glycosylation_sites_count": 103, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G49108TO", "G43417UB", "G47702MW", "G01650EU", "G02815KT", "G06110VR", "G41247ZX", "G47318KU", "G57321FI", "G63628AV", "G64973KT", "G71838YU", "G49582PC", "G74722FL", "G29068FM", "G53434XO", "G58001LT", "G01614ZM", "G81006GJ", "G00033MO", "G32550BI" ], "uniprot_id": "Q92954" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345908" }, { "confidence": "medium", "disease": "Degenerative Hip Joint Disease", "glycan_involvement": "Glycosylation may modulate immune cell interactions.", "mechanism": "CD68+ macrophage infiltration correlates with disease severity and tissue remodeling.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345908" }, { "confidence": "high", "disease": "Degenerative Hip Joint Disease", "glycan_involvement": "O-glycosylation required for anti-adhesive and lubricating properties.", "mechanism": "Lubricin loss is a marker of advanced degeneration in both capsule and labrum.", "protein": "Lubricin", "protein_enriched": { "function": "Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adh", "gene_name": "PRG4", "glycan_count": 23, "glycosylation_sites_count": 103, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G49108TO", "G43417UB", "G47702MW", "G01650EU", "G02815KT", "G06110VR", "G41247ZX", "G47318KU", "G57321FI", "G63628AV", "G64973KT", "G71838YU", "G49582PC", "G74722FL", "G29068FM", "G53434XO", "G58001LT", "G01614ZM", "G81006GJ", "G00033MO", "G32550BI" ], "uniprot_id": "Q92954" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345908" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Upregulated after brain lesions, promotes neurite outgrowth and synapse formation, facilitating neuroplasticity.", "protein": "M6a", "protein_enriched": { "function": "May be involved in neural development. Involved in regulation of osteoblast function and bone formation. Involved in matrix vesicle release by osteoblasts; this function seems to involve maintenance o", "gene_name": "GPM6B", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q13491" }, "relationship_type": "protective", "source_pmcid": "PMC12345952" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "O-glycosylation critical for cell surface expression and interaction.", "mechanism": "Highly expressed in brain tumours, regulates neuronal outgrowth and synaptic density via NGF and CREB pathways.", "protein": "Podoplanin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345952" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "N-glycosylation modulates synaptic function and secretion.", "mechanism": "Secreted by active neurons, acts as a mitogen promoting high-grade glioma proliferation and invasion.", "protein": "Neuroligin-3 (NLGN3)", "protein_enriched": { "function": "Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and may mediate its effect", "gene_name": "NLGN3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZ94" }, "relationship_type": "causal", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Gliosarcoma", "glycan_involvement": "Minor glycosylation, not central to function.", "mechanism": "Upregulated in gliosarcoma, reflects astrocytic activation and reactive gliosis supporting neural repair.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Glycosylation affects vesicle trafficking.", "mechanism": "Increased in peri-tumoural regions, indicates active synaptogenesis and compensatory plasticity.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Gliosarcoma", "glycan_involvement": "Extensive glycosylation required for secretion and function.", "mechanism": "Upregulated, suggests enhanced angiogenesis supporting reorganising neural tissue.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "N-glycosylation essential for cell surface expression.", "mechanism": "Upregulation negatively impacts synaptic stability, may impair beneficial plasticity.", "protein": "MHC I", "relationship_type": "causal", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Gliosarcoma", "glycan_involvement": "O-glycosylation modulates interaction with ligands.", "mechanism": "Upregulated in gliosarcoma, interacts with NGF to promote neurogenesis and synaptic plasticity.", "protein": "Podoplanin", "relationship_type": "biomarker", "source_pmcid": "PMC12345952" }, { "confidence": "medium", "disease": "Ischaemia", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Upregulated after ischaemic injury, facilitates neurite outgrowth and synaptic formation.", "protein": "M6a", "protein_enriched": { "function": "May be involved in neural development. Involved in regulation of osteoblast function and bone formation. Involved in matrix vesicle release by osteoblasts; this function seems to involve maintenance o", "gene_name": "GPM6B", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q13491" }, "relationship_type": "protective", "source_pmcid": "PMC12345952" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation affects synaptic function.", "mechanism": "Altered NLGN3 secretion may contribute to epileptogenesis in tumoural brain.", "protein": "Neuroligin-3 (NLGN3)", "protein_enriched": { "function": "Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and may mediate its effect", "gene_name": "NLGN3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZ94" }, "relationship_type": "causal", "source_pmcid": "PMC12345952" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and affects immunogenicity.", "mechanism": "Spike glycoprotein mediates viral entry and is the main target of neutralizing antibodies and vaccine-induced immunity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG is N-glycosylated; glycosylation modulates effector function.", "mechanism": "Serum IgG-S levels indicate humoral immune response to SARS-CoV-2 vaccination.", "protein": "IgG-S (anti-Spike IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation affects antibody stability and function.", "mechanism": "IgG-N positivity indicates prior SARS-CoV-2 infection.", "protein": "IgG-N (anti-Nucleocapsid IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IFN-\u03b3 is glycosylated, which may affect secretion and activity.", "mechanism": "IFN-\u03b3 release upon antigen stimulation reflects cellular immune response to vaccination.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation influences vaccine antigenicity and immune recognition.", "mechanism": "Spike glycoprotein is the antigenic target in mRNA vaccines for IBD patients.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic target", "source_pmcid": "PMC12346008" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "IgG glycosylation may be altered in chronic inflammation, affecting function.", "mechanism": "IgG-S levels used to monitor vaccine response in IBD patients under immunosuppressive therapy.", "protein": "IgG-S (anti-Spike IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation may modulate cytokine activity.", "mechanism": "IFN-\u03b3 release assay quantifies cellular vaccine response in IBD patients.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "IgG glycosylation can influence antibody function in UC.", "mechanism": "IgG-S titers reflect vaccine-induced immunity in UC patients.", "protein": "IgG-S (anti-Spike IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "medium", "disease": "Crohn\u2019s Disease", "glycan_involvement": "IgG glycosylation may be altered in CD.", "mechanism": "IgG-S titers used to assess vaccine response in CD patients.", "protein": "IgG-S (anti-Spike IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation critical for folding, immune evasion, and vaccine efficacy.", "mechanism": "Spike glycoprotein is the basis for mRNA vaccine design.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic target", "source_pmcid": "PMC12346008" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates receptor activation and ligand binding.", "mechanism": "Activated glycoprotein IIb/IIIa on platelets is targeted by PET radiotracer (18F-GP1) to detect active thrombus formation.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346019" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "CD44 is heavily glycosylated; glycosylation modulates HA binding and cell interactions.", "mechanism": "Promotes cell proliferation, migration, adhesion, and chemoresistance; high expression correlates with poor prognosis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "CD133 is glycosylated; glycosylation affects epitope recognition and stem cell marker function.", "mechanism": "Associated with tumorigenicity, stemness, and therapy resistance; high expression linked to poor prognosis.", "protein": "CD133 (Prominin-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "medium", "disease": "Endometrial Cancer", "glycan_involvement": "EpCAM is N-glycosylated; glycosylation influences cell adhesion and migration.", "mechanism": "Downregulation favors poor prognosis and cancer cell invasion.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "ALDH1A1 is glycosylated; glycosylation may affect enzyme stability and localization.", "mechanism": "High ALDH1A1 expression predicts reduced survival and increased stemness/EMT.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "PD-L1 N-glycosylation stabilizes protein and affects immune evasion.", "mechanism": "Modulates EMT, CSC phenotype, metastasis, and therapy resistance; upregulated by OCT4/EMT.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "Potential O-glycosylation; may affect nuclear localization and stability.", "mechanism": "Overexpression correlates with advanced grade, poor prognosis, and tumor relapse.", "protein": "SOX2", "protein_enriched": { "function": "Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarit", "gene_name": "SOX2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "P48431" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "Potential O-glycosylation; may influence transcriptional activity.", "mechanism": "Correlates with poor outcome and disease-free survival; regulates CSC pluripotency.", "protein": "OCT4 (POU5F1)", "protein_enriched": { "function": "Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Forms a trimeric complex with SOX2 or SOX15 on DNA and controls the expression of a number of genes involved in embryonic develop", "gene_name": "POU5F1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01860" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Endometrial Cancer", "glycan_involvement": "Potential O-glycosylation; may affect protein stability.", "mechanism": "Predicts poor prognosis and recurrence; maintains CSC stemness via JAK/STAT3 pathway.", "protein": "NANOG", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "medium", "disease": "Endometrial Cancer", "glycan_involvement": "N-glycosylation regulates cell adhesion and EMT.", "mechanism": "Loss during EMT promotes invasion, metastasis, and poor survival.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Chemoresistant Endometrial Cancer", "glycan_involvement": "Glycosylation modulates CD44-mediated drug resistance.", "mechanism": "CD44+ CSCs drive chemoresistance and tumor relapse.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346045" }, { "confidence": "high", "disease": "Thyroid enlargement (goiter)", "glycan_involvement": "N-glycosylation affects secretion and immunogenicity.", "mechanism": "Thyroglobulin levels reflect thyroid tissue mass and function.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "high", "disease": "Congenital hypothyroidism", "glycan_involvement": "N-glycosylation required for enzymatic activity.", "mechanism": "Defective TPO impairs thyroid hormone synthesis.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "causal", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Thyroid enlargement (goiter)", "glycan_involvement": "O-glycosylation modulates hormone stability.", "mechanism": "Negative correlation: lower calcitonin associated with larger thyroid volume in children.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "high", "disease": "Thyroid enlargement (goiter)", "glycan_involvement": "N-glycosylation essential for receptor binding.", "mechanism": "TSH stimulates thyroid growth and hormone production.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation affects hormone transport.", "mechanism": "Low FT4 indicates reduced thyroid function.", "protein": "Free thyroxine (FT4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Thyroid enlargement (goiter)", "glycan_involvement": "Glycosylation modulates hormone bioavailability.", "mechanism": "Negative correlation: lower FT3 associated with larger thyroid volume.", "protein": "Free triiodothyronine (FT3)", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "low", "disease": "Thyroid enlargement (goiter)", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Correlation varies by age group; may reflect calcium metabolism impact on thyroid.", "protein": "Parathormone (PTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Thyroid nodules", "glycan_involvement": "Fc glycosylation affects antibody effector function.", "mechanism": "Autoantibodies indicate autoimmune thyroid disease risk.", "protein": "Anti-thyroid peroxidase antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Fc glycosylation modulates immune response.", "mechanism": "Autoantibodies may interfere with thyroglobulin measurement in cancer monitoring.", "protein": "Thyroglobulin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Altered glycosylation may affect antigenicity.", "mechanism": "Reduced TPO expression is associated with malignancy.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC12346054" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation facilitates immune recognition and TLR4 activation.", "mechanism": "Envelope glycoprotein involved in viral entry and immune response; targeted for vaccine development.", "protein": "B6R", "protein_enriched": { "function": "Binds to chondroitin sulfate on the cell surface to provide virion attachment to target cell", "gene_name": "OPG105", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation critical for antigenicity and immune activation.", "mechanism": "Surface glycoprotein mediates heparin binding and is immunodominant; stimulates CTL, HTL, and antibody responses.", "protein": "H3L", "protein_enriched": { "function": "Acts with RNA polymerase to initiate transcription from early gene promoters. Is recruited by the RPO-associated protein of 94 kDa RAP94/OPG109 to form the early transcription complex, which also cont", "gene_name": "E6R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may affect chemokine binding and immune evasion.", "mechanism": "Chemokine-binding glycoprotein modulates host immune response and prevents apoptosis, facilitating viral infection.", "protein": "J3R/J1L", "protein_enriched": { "function": "", "gene_name": "E1R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y7" }, "relationship_type": "causal", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation enhances immunogenicity.", "mechanism": "Structural glycoprotein induces antibody production in vivo.", "protein": "E4R", "protein_enriched": { "function": "Late protein which is part of a large complex required for early virion morphogenesis. This complex participates in the formation of virosomes and the incorporation of virosomal contents into nascent ", "gene_name": "E3R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Membrane glycoprotein implicated in pathogenesis and CTL stimulation.", "protein": "B9R", "protein_enriched": { "function": "", "gene_name": "E7R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y1" }, "relationship_type": "causal", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation supports antigen presentation.", "mechanism": "Structural glycoprotein homologous to vaccinia A38L, crucial for MHC II and HTL activation.", "protein": "A40L", "protein_enriched": { "function": "", "gene_name": "E9R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4X9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation aids immune recognition.", "mechanism": "Structural glycoprotein homologous to vaccinia K2L, important for MHC II and HTL activation.", "protein": "C2L", "protein_enriched": { "function": "Multifunctional protein required for genome uncoating and replication. Major viral uncoating protein that is required for the release of the viral genome from incoming viral cores containing the viral", "gene_name": "E5R", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Associated glycosylation may affect immunogenicity.", "mechanism": "DNA polymerase protein stimulates CD8+ T-cell and IFN-\u03b3 release.", "protein": "F8L", "protein_enriched": { "function": "Late protein which is part of a large complex required for early virion morphogenesis. This complex participates in the formation of virosomes and the incorporation of virosomal contents into nascent ", "gene_name": "E2L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8V4Y6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346078" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation required for GM1 binding and adjuvant activity.", "mechanism": "Adjuvant glycoprotein enhances immune response by binding GM1 ganglioside receptors.", "protein": "Cholera toxin B subunit (CTB)", "protein_enriched": { "function": "The B subunit pentameric ring directs the A subunit to its target by binding to the GM1 gangliosides present on the surface of the intestinal epithelial cells. It can bind five GM1 gangliosides. It ha", "gene_name": "ctxB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01556" }, "relationship_type": "protective", "source_pmcid": "PMC12346078" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation of TLR4 and viral proteins is essential for interaction and immune signaling.", "mechanism": "Host immune receptor glycoprotein mediates vaccine-induced immune activation via recognition of glycosylated viral proteins.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "protective", "source_pmcid": "PMC12346078" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding, immune evasion, and antigenicity.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2 binding, determining infectivity and pathogenesis.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12346103" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans shield epitopes, affecting antibody accessibility and vaccine efficacy.", "mechanism": "Spike RBD is targeted by neutralizing antibodies and vaccine platforms (e.g., ferritin nanocages).", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346103" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation may influence Spike binding affinity.", "mechanism": "ACE2 is the host receptor for Spike, enabling SARS-CoV-2 cell entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346103" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shielding on Spike may affect B38 binding.", "mechanism": "B38 binds Spike RBD at ACE2 interface, blocking viral entry and neutralizing infection.", "protein": "B38 monoclonal antibody", "relationship_type": "protective", "source_pmcid": "PMC12346103" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation at RBD may modulate VVH-72 binding.", "mechanism": "VVH-72 binds Spike RBD at a site distinct from ACE2, allowing simultaneous receptor and antibody binding.", "protein": "VVH-72 monoclonal antibody", "relationship_type": "protective", "source_pmcid": "PMC12346103" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Ferritin itself is not glycosylated; displays glycosylated antigens.", "mechanism": "Ferritin nanocages display Spike RBD, enhancing immunogenicity and stability for vaccine development.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346103" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation affects infectivity and immune recognition.", "mechanism": "Spike glycoprotein is essential for viral attachment and entry.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12346103" }, { "confidence": "medium", "disease": "MERS-CoV infection", "glycan_involvement": "Glycosylation patterns may influence cross-reactivity.", "mechanism": "Mosaic ferritin-based vaccines displaying Spike can induce cross-protective immunity.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346103" }, { "confidence": "medium", "disease": "SARS-CoV infection", "glycan_involvement": "Glycosylation impacts antigenicity and immune response.", "mechanism": "Ferritin nanocages displaying Spike can elicit immune responses against SARS-CoV.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346103" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "Spike glycoprotein is the main antigen detected in diagnostic assays.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12346103" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Mediates binding to PSGL-1 via glycosylated domains.", "mechanism": "Promotes platelet-leukocyte aggregate formation, driving thromboinflammation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Glycosylation affects receptor binding and stability.", "mechanism": "Released from activated platelets, triggers endothelial activation and leukocyte recruitment.", "protein": "CD40 ligand (CD40L)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346139" }, { "confidence": "medium", "disease": "Delayed wound healing", "glycan_involvement": "N-glycosylation modulates cell-cell interactions.", "mechanism": "Upregulated by platelet CD40L, facilitates leukocyte adhesion and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12346139" }, { "confidence": "medium", "disease": "Organ dysfunction", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "Promotes monocyte adhesion, amplifies inflammatory response post-surgery.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation influences ligand binding and activation.", "mechanism": "Central to platelet aggregation; targeted by antiplatelet drugs.", "protein": "GPIIb/IIIa (Integrin \u03b1IIb\u03b23)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Regulates platelet production; agonists used to treat low platelet counts.", "protein": "Thrombopoietin receptor (MPL)", "protein_enriched": { "function": "Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. Upon activation by THPO, induces rapid tyrosine phosphorylation and a", "gene_name": "MPL", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G25637MV" ], "uniprot_id": "P40238" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "O-glycosylation essential for selectin binding.", "mechanism": "Ligand for P-selectin, mediates platelet-leukocyte interactions.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346139" }, { "confidence": "medium", "disease": "Microvascular occlusion", "glycan_involvement": "Surface glycoproteins mediate endothelial interactions.", "mechanism": "Carry procoagulant glycoproteins, promote thromboinflammation.", "protein": "Platelet-derived microparticles (PMPs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Cancer (colorectal, hepatobiliary, lung, ovarian)", "glycan_involvement": "Glycosylation modulates immune signaling.", "mechanism": "Elevated sCD40L linked to cancer progression, metastasis, and VTE.", "protein": "CD40 ligand (CD40L)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346139" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects ligand recognition.", "mechanism": "Ligand binding triggers platelet activation and aggregation.", "protein": "CLEC-2", "protein_enriched": { "function": "Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro) (PubMed:12804604, PubMed:17585783, PubMed:18198127). The biological function and the GSH-depende", "gene_name": "PTGES2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7Z7" }, "relationship_type": "causal", "source_pmcid": "PMC12346139" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC) with pleural dissemination (M1a)", "glycan_involvement": "CEA is a heavily N-glycosylated glycoprotein; glycosylation is essential for its secretion and stability in serum.", "mechanism": "Elevated serum CEA levels and upward trends within 3 months post-diagnosis predict poor prognosis and disease progression.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation enables CEA's release into circulation and detection.", "mechanism": "Serum CEA is widely used for monitoring disease progression and recurrence.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Gastric carcinoma", "glycan_involvement": "Glycosylation is required for CEA's function as a serum marker.", "mechanism": "CEA levels correlate with disease status and prognosis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "medium", "disease": "Gynecologic cancer", "glycan_involvement": "Glycosylation facilitates CEA's stability and detectability.", "mechanism": "CEA is used as a supplementary marker for disease monitoring.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation is critical for CEA's serum presence.", "mechanism": "CEA is used for prognosis and disease monitoring.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "medium", "disease": "Brain metastasis (secondary to NSCLC)", "glycan_involvement": "Glycosylation supports CEA's role as a circulating marker.", "mechanism": "Elevated CEA may indicate risk of extrathoracic progression including brain metastasis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "low", "disease": "Non-small cell lung cancer (NSCLC) with pleural dissemination (M1a)", "glycan_involvement": "Glycosylation modulates CEA's adhesive properties and tumor cell interactions.", "mechanism": "CEA may play a role in tumorigenesis and cell adhesion, facilitating metastatic spread.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "causal", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC) with pleural dissemination (M1a)", "glycan_involvement": "Proper glycosylation ensures accurate measurement of CEA trends.", "mechanism": "Low or decreasing CEA levels within 3 months post-diagnosis are associated with improved progression-free survival.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "protective", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC) with pleural dissemination (M1a)", "glycan_involvement": "Glycosylation is necessary for CEA's secretion and detection in serum.", "mechanism": "Longitudinal monitoring of CEA is more sensitive than ctDNA for predicting progression in non-shedding tumors.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC) with pleural dissemination (M1a)", "glycan_involvement": "N-glycosylation is essential for CEA's function as a biomarker.", "mechanism": "Early increase in CEA levels is a cost-effective predictor of disease progression.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346199" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "PSA is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "PSA is secreted by prostate epithelial cells and elevated in blood during prostate cancer.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Benign Prostatic Hyperplasia (BPH)", "glycan_involvement": "Glycosylation may differ between benign and malignant PSA forms.", "mechanism": "PSA levels can be elevated in BPH due to increased secretion from benign tissue.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "medium", "disease": "Prostatitis", "glycan_involvement": "Glycosylation status may affect PSA clearance.", "mechanism": "Inflammation increases PSA secretion into blood.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)", "glycan_involvement": "Glycosylation impacts PSA detection and quantification.", "mechanism": "PSA levels are used to monitor disease progression and response to therapy.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "medium", "disease": "Castration-Resistant Prostate Cancer (CRPC)", "glycan_involvement": "Altered glycosylation may occur in advanced disease.", "mechanism": "PSA remains a key marker for disease monitoring in CRPC.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "medium", "disease": "Biochemically Recurrent Prostate Cancer (BCR)", "glycan_involvement": "Glycosylation may affect PSA half-life.", "mechanism": "Rising PSA after treatment indicates biochemical recurrence.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "PSMA is a glycoprotein; glycosylation affects its cell surface localization and antibody recognition.", "mechanism": "PSMA is overexpressed on prostate cancer cells and targeted by imaging agents and therapies.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)", "glycan_involvement": "Glycosylation modulates PSMA's accessibility to imaging agents.", "mechanism": "PSMA-targeted PET imaging is used for staging and detection of metastases.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346201" }, { "confidence": "medium", "disease": "Castration-Resistant Prostate Cancer (CRPC)", "glycan_involvement": "Glycosylation may influence therapeutic efficacy.", "mechanism": "PSMA-targeted therapies are under investigation for CRPC.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation affects PSA measurement accuracy.", "mechanism": "Rapid and deep PSA decline after apalutamide therapy is associated with improved survival.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12346201" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "BDNF is a glycoprotein; glycosylation may affect secretion and stability, but specific glycan roles not detailed.", "mechanism": "Plasma BDNF is significantly elevated in early-stage PBC compared to controls.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate BDNF's stability and receptor interactions; not directly addressed.", "mechanism": "Higher plasma BDNF correlates with lower liver stiffness and fibrosis scores, suggesting a protective or anti-fibrotic association.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Minimal hepatic encephalopathy (MHE)", "glycan_involvement": "No direct evidence for glycan involvement in this context.", "mechanism": "BDNF is elevated in PBC regardless of MHE status; not directly associated with cognitive impairment.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Fatigue in PBC", "glycan_involvement": "No direct evidence for glycan involvement.", "mechanism": "No significant correlation between plasma BDNF and fatigue severity in PBC.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect BDNF's function; not discussed in detail.", "mechanism": "Previous studies show elevated BDNF in NAFLD, correlating with hepatic injury markers.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "sGPV is a glycoprotein; glycosylation affects its cleavage and release.", "mechanism": "Elevated plasma sGPV indicates increased thrombin-induced platelet activation in early-stage PBC.", "protein": "sGPV", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Liver cirrhosis with hepatic encephalopathy", "glycan_involvement": "No direct evidence for glycan involvement.", "mechanism": "Reduced serum BDNF in cirrhotic patients with hepatic encephalopathy; negative correlation with bilirubin and INR.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Chronic hepatitis B-induced liver fibrosis", "glycan_involvement": "Glycosylation may affect BDNF's activity; not specified.", "mechanism": "Experimental data show BDNF upregulation in fibrotic liver tissue and stimulation of hepatic stellate cells.", "protein": "BDNF", "relationship_type": "causal", "source_pmcid": "PMC12346204" }, { "confidence": "low", "disease": "Systemic inflammation in PBC", "glycan_involvement": "No direct evidence for glycan involvement.", "mechanism": "Trend toward association between plasma BDNF and IL-6 levels, suggesting neuroimmune regulation.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "medium", "disease": "Cognitive impairment in PBC", "glycan_involvement": "No direct evidence for glycan involvement.", "mechanism": "No independent association between plasma BDNF and cognitive dysfunction in PBC.", "protein": "BDNF", "relationship_type": "biomarker", "source_pmcid": "PMC12346204" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation modulates integrin function and cell adhesion.", "mechanism": "Upregulated by TGF\u03b2, drives fibroblast activation and ECM deposition.", "protein": "ITGAL (Integrin alpha-L)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "N-glycosylation required for FURIN maturation and activity.", "mechanism": "Regulates activation of profibrotic signaling molecules.", "protein": "FURIN", "relationship_type": "causal", "source_pmcid": "PMC12346348" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Potential glycosylation may affect stability and localization.", "mechanism": "Master regulator of TGF\u03b2-triggered fibroblast activation.", "protein": "DUSP9", "protein_enriched": { "function": "Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphat", "gene_name": "PPIP5K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43314" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "N-glycosylation essential for secretion and activity.", "mechanism": "Promotes fibroblast activation via angiotensin signaling.", "protein": "AGT (Angiotensinogen)", "protein_enriched": { "function": "Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis", "gene_name": "AGT", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G10133VD" ], "uniprot_id": "P01019" }, "relationship_type": "causal", "source_pmcid": "PMC12346348" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation affects receptor trafficking and signaling.", "mechanism": "Receptor mediates angiotensin II effects on fibroblast activation.", "protein": "AGTR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Hydroxylation and glycosylation critical for collagen fibril formation.", "mechanism": "Major ECM component deposited by activated fibroblasts.", "protein": "Col1A1 (Collagen type I alpha 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346348" }, { "confidence": "low", "disease": "Cardiac fibrosis", "glycan_involvement": "Potential glycosylation may modulate proteasome assembly.", "mechanism": "Regulates proteasome activity in fibroblast activation.", "protein": "PSMA7", "protein_enriched": { "function": "Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with dif", "gene_name": "PSMA7", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14818" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "low", "disease": "Cardiac fibrosis", "glycan_involvement": "Potential glycosylation may affect kinase activity.", "mechanism": "Kinase involved in cell cycle and fibroblast proliferation.", "protein": "PLK2", "protein_enriched": { "function": "Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins that ar", "gene_name": "PLK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NYY3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "low", "disease": "Cardiac fibrosis", "glycan_involvement": "Potential glycosylation may affect membrane localization.", "mechanism": "Regulates fibroblast phenotype and signaling.", "protein": "MTUS1", "protein_enriched": { "function": "Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regula", "gene_name": "EPN1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "Q9Y6I3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "low", "disease": "Cardiac fibrosis", "glycan_involvement": "Potential glycosylation may regulate phosphatase activity.", "mechanism": "Phosphatase modulates signaling pathways in fibroblast activation.", "protein": "PTPN6", "protein_enriched": { "function": "Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephos", "gene_name": "PTPN6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P29350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346348" }, { "confidence": "high", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "CD45 is a heavily glycosylated protein; glycosylation is essential for its cell surface expression and function.", "mechanism": "CD45 is required for neutrophil recruitment, cytokine release, and ROS production; its deficiency abrogates arthritis development.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "causal", "source_pmcid": "PMC12346378" }, { "confidence": "high", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "CD148 is glycosylated; glycosylation affects its stability and localization.", "mechanism": "CD148 deficiency delays arthritis onset and reduces ROS production, but does not prevent neutrophil infiltration.", "protein": "CD148", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q60681" }, "relationship_type": "modulatory", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may influence antibody accessibility and therapeutic targeting.", "mechanism": "Targeting CD45 may reduce neutrophil recruitment and effector functions, potentially limiting tissue damage.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect receptor function and drug targeting.", "mechanism": "Modulation of CD148 could alter neutrophil activation and ROS production, impacting disease severity.", "protein": "CD148", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q60681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Glycosylation required for proper CD45 function.", "mechanism": "CD45-deficient leukocytes show impaired SFK activation and reduced migration, affecting infection response.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "causal", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "CD148 deficiency increases neutrophil recruitment but decreases phagocytosis.", "protein": "CD148", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q60681" }, "relationship_type": "modulatory", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "C5a is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "C5a levels in synovial fluid correlate with neutrophil recruitment and inflammation.", "protein": "C5a", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11453" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "CXCL1 is glycosylated; glycosylation may affect secretion and receptor binding.", "mechanism": "CXCL1 is a dominant proinflammatory chemokine in synovial fluid during arthritis.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects stability and activity.", "mechanism": "IL-6 is elevated in synovial fluid during arthritis, reflecting inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346378" }, { "confidence": "medium", "disease": "Inflammatory arthritis (STIA model)", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 release by neutrophils is altered by CD45/CD148 deficiency, impacting inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346378" }, { "confidence": "high", "disease": "Upper tract urothelial carcinoma (UTUC)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated serum AST (relative to ALT) reflects metabolic reprogramming in aggressive UTUC tumors.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "high", "disease": "Upper tract urothelial carcinoma (UTUC)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its serum half-life.", "mechanism": "Lower ALT (relative to AST) is part of the De Ritis ratio, indicating poor prognosis in UTUC.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "high", "disease": "Intravesical recurrence after nephroureterectomy", "glycan_involvement": "Ratio reflects levels of glycoproteins AST and ALT; glycosylation may influence detection.", "mechanism": "High De Ritis ratio independently predicts increased risk of bladder tumor recurrence post-surgery.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "high", "disease": "Cancer-specific mortality in UTUC", "glycan_involvement": "Indirect; glycosylation of AST/ALT may affect serum measurement.", "mechanism": "High ratio is associated with significantly worse cancer-specific survival.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "medium", "disease": "Bladder cancer (BCa)", "glycan_involvement": "Indirect; glycosylation status may affect protein stability.", "mechanism": "High ratio predicts recurrence and poor outcomes in synchronous bladder cancer.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "medium", "disease": "Cancer-specific mortality in UTUC", "glycan_involvement": "AST glycosylation may modulate serum levels.", "mechanism": "Elevated AST is part of the De Ritis ratio, correlating with aggressive tumor biology and mortality.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "medium", "disease": "Cancer-specific mortality in UTUC", "glycan_involvement": "ALT glycosylation may affect its clearance.", "mechanism": "Lower ALT (with high AST) is associated with poor cancer-specific survival.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "medium", "disease": "Muscle-invasive bladder cancer", "glycan_involvement": "Indirect; glycosylation may affect AST/ALT serum levels.", "mechanism": "High ratio predicts worse overall survival after radical cystectomy.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Indirect; glycosylation may affect protein stability.", "mechanism": "High ratio associated with poor outcomes in other urologic cancers.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "low", "disease": "Renal cell carcinoma", "glycan_involvement": "Indirect; glycosylation may affect serum detection.", "mechanism": "High ratio linked to adverse prognosis in renal cell carcinoma.", "protein": "De Ritis ratio (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12346446" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "GGT is a glycoprotein; altered glycosylation may affect its stability and serum levels.", "mechanism": "Elevated GGT reflects hepatocellular injury and cholestasis in cirrhosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "AST is glycosylated; glycan changes may influence its clearance.", "mechanism": "Elevated AST indicates hepatocyte damage in cirrhosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "ALT glycosylation may affect its serum half-life.", "mechanism": "ALT elevation is a marker of liver cell injury in cirrhosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin is N-glycosylated; glycan changes may affect its function and stability.", "mechanism": "Low albumin reflects impaired hepatic synthetic function and malnutrition.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Lipoproteins are glycosylated; glycan modifications affect lipid transport.", "mechanism": "Altered triglyceride levels reflect changes in hepatic lipid metabolism.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "LDL glycosylation influences receptor binding and clearance.", "mechanism": "LDL levels may be altered due to impaired hepatic lipid processing.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered N-glycosylation patterns (e.g., increased carbohydrate-deficient transferrin) are diagnostic.", "mechanism": "Transferrin glycoforms are altered in cirrhosis, reflecting hepatic dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation affects ceruloplasmin stability and copper transport.", "mechanism": "Ceruloplasmin levels may decrease in advanced liver disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "Glycosylation status may influence albumin's nutritional biomarker role.", "mechanism": "Low albumin is a marker of malnutrition in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate GGT activity and serum levels.", "mechanism": "Elevated GGT is common in NAFLD and reflects oxidative stress.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346458" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "Defective N-glycosylation impairs folding and trafficking.", "mechanism": "Mutations in TG cause misfolding, leading to deficient thyroid hormone synthesis.", "protein": "Thyroglobulin (Tg)", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine resid", "gene_name": "TG", "glycan_count": 1, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G64527OM" ], "uniprot_id": "P01267" }, "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "Impaired glycosylation leads to ER retention.", "mechanism": "Misfolded mutant Tg accumulates in ER, causing ER stress and loss of hormone production.", "protein": "Mutant Tg (p.L2263P)", "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "high", "disease": "Goiter", "glycan_involvement": "Misfolded glycoprotein fails to exit ER, stimulating TSH-driven proliferation.", "mechanism": "Defective Tg triggers TSH elevation and thyroid overgrowth.", "protein": "Thyroglobulin (Tg)", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine resid", "gene_name": "TG", "glycan_count": 1, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G64527OM" ], "uniprot_id": "P01267" }, "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "Proper N-glycosylation enables secretion and function.", "mechanism": "ChEL-KI mice produce T3 via ChEL domain, partially rescuing hypothyroid phenotypes.", "protein": "ChEL domain of Tg", "relationship_type": "protective", "source_pmcid": "PMC12346460" }, { "confidence": "high", "disease": "Goiter", "glycan_involvement": "Efficient glycosylation allows increased protein secretion and gland growth.", "mechanism": "TSH stimulation of ChEL-KI mice leads to large goiter despite normal T3.", "protein": "ChEL domain of Tg", "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "medium", "disease": "Impaired body growth", "glycan_involvement": "Golgi-type N-glycans enable proper trafficking and hormone production.", "mechanism": "ChEL-KI mice have improved growth compared to Tg mutants due to normal T3.", "protein": "ChEL domain of Tg", "relationship_type": "protective", "source_pmcid": "PMC12346460" }, { "confidence": "medium", "disease": "Neurological impairments", "glycan_involvement": "Glycosylation enables secretion but does not compensate for local T4-to-T3 conversion in CNS.", "mechanism": "Normal serum T3 from ChEL domain does not fully rescue CNS deficits due to lack of T4.", "protein": "ChEL domain of Tg", "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "medium", "disease": "Anxiety-like behavior", "glycan_involvement": "Glycosylation enables hormone production but does not restore CNS function.", "mechanism": "ChEL-KI mice show increased anxiety-like behavior despite normal T3.", "protein": "ChEL domain of Tg", "relationship_type": "causal", "source_pmcid": "PMC12346460" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Not directly discussed.", "mechanism": "ME1 expression is reduced in hypothyroid mice with low T3, normal in ChEL-KI mice.", "protein": "Malic Enzyme 1 (ME1)", "protein_enriched": { "function": "Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage ", "gene_name": "MAPKAPK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49137" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346460" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Not directly discussed.", "mechanism": "D1 expression is reduced in hypothyroid mice with low T3, normal in ChEL-KI mice.", "protein": "Type 1 Deiodinase (D1)", "protein_enriched": { "function": "RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/o", "gene_name": "Qki", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QYS9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346460" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycation (non-enzymatic addition of glucose to hemoglobin).", "mechanism": "HbA1c reflects average blood glucose via non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Thyroid abnormalities (hypothyroidism)", "glycan_involvement": "TSH is a glycoprotein hormone; glycosylation affects stability and receptor binding.", "mechanism": "TSH levels indicate thyroid function; elevated in hypothyroidism.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Medullary Thyroid Carcinoma (MTC)", "glycan_involvement": "Calcitonin is glycosylated, affecting secretion and stability.", "mechanism": "Elevated calcitonin is a marker for MTC; produced by C-cells.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Amylase is glycosylated, influencing secretion and activity.", "mechanism": "Elevated amylase indicates pancreatic inflammation.", "protein": "Pancreatic amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Lipase glycosylation affects enzyme stability and function.", "mechanism": "Elevated lipase is diagnostic for pancreatitis.", "protein": "Pancreatic lipase", "protein_enriched": { "function": "Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows consi", "gene_name": "PNLIP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL particles are glycosylated, affecting clearance and atherogenicity.", "mechanism": "High LDL is a risk factor for dyslipidemia and cardiovascular disease.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory and cholesterol efflux functions.", "mechanism": "Low HDL is associated with increased cardiovascular risk.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "High HbA1c (poor glycemic control) increases risk of retinopathy.", "protein": "HbA1c", "relationship_type": "causal", "source_pmcid": "PMC12346479" }, { "confidence": "medium", "disease": "Medullary Thyroid Carcinoma (MTC)", "glycan_involvement": "TSH glycosylation affects hormone activity and detection.", "mechanism": "TSH levels may be altered in thyroid cancer.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "medium", "disease": "Thyroid abnormalities (hypothyroidism)", "glycan_involvement": "Glycosylation impacts calcitonin secretion.", "mechanism": "Calcitonin levels may be altered in thyroid dysfunction.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346479" }, { "confidence": "high", "disease": "Sporadic Alzheimer's disease (sAD)", "glycan_involvement": "IGF-1 is a glycoprotein; glycosylation is required for stability and receptor binding.", "mechanism": "Central administration of IGF-1 reduces neuropsychiatric symptoms and peripheral inflammation in sAD rat model.", "protein": "IGF-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346486" }, { "confidence": "high", "disease": "Depression", "glycan_involvement": "Glycosylation affects IGF-1 bioactivity and half-life.", "mechanism": "IGF-1 administration reduces anhedonia (depression-like behavior) in sAD model.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12346486" }, { "confidence": "high", "disease": "Anxiety", "glycan_involvement": "Glycosylation required for IGF-1 receptor interaction.", "mechanism": "IGF-1 reduces anxiety-like behavior in sAD model.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12346486" }, { "confidence": "high", "disease": "Peripheral inflammation", "glycan_involvement": "Glycosylation modulates IGF-1 secretion and immune effects.", "mechanism": "IGF-1 administration decreases leukocyte, lymphocyte, monocyte, granulocyte, and IL-6 levels.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12346486" }, { "confidence": "high", "disease": "Sporadic Alzheimer's disease (sAD)", "glycan_involvement": "CD68 is a heavily glycosylated lysosomal protein; glycosylation affects phagocytic activity.", "mechanism": "CD68+ microglia activation correlates with A\u03b2 plaques and neuropsychiatric symptoms.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. 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R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346605" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "HA\u2013RHAMM interaction relevant for immune modulation.", "mechanism": "High RHAMM expression associated with poor prognosis; RHAMM-derived peptide vaccines elicit anti-tumor T-cell responses.", "protein": "RHAMM (CD168)", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346605" }, { "confidence": "high", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "HA\u2013RHAMM axis may influence leukemic cell migration.", "mechanism": "RHAMM highly upregulated; peptide vaccines (e.g., RHAMM-R3) induce specific CD8+ T-cell responses and anti-leukemia effects.", "protein": "RHAMM (CD168)", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346605" }, { "confidence": "high", "disease": "Chronic myeloid leukemia (CML)", "glycan_involvement": "HA\u2013RHAMM interaction may affect immune recognition.", "mechanism": "RHAMM-derived peptides induce CD8+ T-cell responses; potential for immunotherapy.", "protein": "RHAMM (CD168)", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. 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R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346605" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "HA\u2013RHAMM signaling implicated in tumor microenvironment modulation.", "mechanism": "Exosomal lncRNA HMMR-AS1 modulates RHAMM, influencing macrophage polarization and tumor progression.", "protein": "RHAMM (CD168)", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346605" }, { "confidence": "medium", "disease": "Malignant peripheral nerve sheath tumor", "glycan_involvement": "Not specified.", "mechanism": "Genomic reduction of RHAMM linked to tumor development, suggesting a context-dependent tumor suppressor role.", "protein": "RHAMM (CD168)", "protein_enriched": { "function": "Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. R", "gene_name": "P3H4", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G14972EH", "G15664MX", "G22572EH", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83633GK", "G49108TO", "G72065MN" ], "uniprot_id": "Q92791" }, "relationship_type": "protective", "source_pmcid": "PMC12346605" }, { "confidence": "high", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux of docetaxel reduces intracellular drug concentration, leading to resistance.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12346647" }, { "confidence": "high", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "N-glycosylation affects transporter stability and function.", "mechanism": "Efflux transporter decreases taxane sensitivity.", "protein": "ABCC10 (MRP7)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent ", "gene_name": "ABCC10", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q5T3U5" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "N-glycosylation modulates surface expression.", "mechanism": "Efflux of taxanes contributes to resistance.", "protein": "ABCG2 (BCRP)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12346647" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Potential O-glycosylation; not detailed in article.", "mechanism": "Promotes EMT, stemness, and resistance via PI3K/Akt and NF-\u03baB activation.", "protein": "Fascin (FSCN1)", "relationship_type": "therapeutic_target/biomarker/causal", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "Possible O-glycosylation; not specified.", "mechanism": "Inhibits apoptosis, co-expressed with TUBB3, linked to poor response.", "protein": "Survivin (BIRC5)", "protein_enriched": { "function": "Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a c", "gene_name": "BIRC5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15392" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "Possible O-glycosylation; not specified.", "mechanism": "Inhibits caspase activation, upregulated in fascin-positive cells.", "protein": "XIAP", "protein_enriched": { "function": "Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as", "gene_name": "XIAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P98170" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "Possible O-glycosylation; not specified.", "mechanism": "Suppresses apoptosis, upregulated in fascin-positive, chemoresistant cells.", "protein": "Livin (BIRC7)", "protein_enriched": { "function": "Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control (PubMed:11024045, PubMed:11084335, P", "gene_name": "BIRC7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96CA5" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346647" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding and stemness.", "mechanism": "Marks cancer stem cells (CD44+/CD24\u2212), associated with resistance and tumour repopulation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "High ALDH activity marks CSCs, which are resistant to docetaxel.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Docetaxel-resistant breast cancer", "glycan_involvement": "Predicted glycoprotein; glycosylation may affect membrane localization.", "mechanism": "Upregulated via circUBR5/miR-340-5p axis, promotes ribosome biogenesis and resistance.", "protein": "CMTM6", "protein_enriched": { "function": "May play a role in tumor angiogenesis", "gene_name": "PLXDC2", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08918WF", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G57776ZS", "G70232NH", "G79666IR", "G84452RH", "G90659AW", "G00912UN", "G04657PL", "G20210JR", "G23294PN", "G40834TG", "G40926MX", "G43669FQ", "G46691LC", "G51653BI", "G59324HL", "G59626AS", "G63041LO", "G83646BJ", "G87123QX", "G92062TF", "G90382BL", "G53434XO", "G29068FM", "G43417UB", "G57321FI" ], "uniprot_id": "Q6UX71" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12346647" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "AMBP is a glycoprotein; glycosylation may affect stability and function in inflammation.", "mechanism": "Downregulation leads to overactivation of alternative complement pathway and increased inflammation.", "protein": "AMBP", "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "low", "disease": "Huntington's Disease", "glycan_involvement": "Glycosylation status may influence AMBP's anti-inflammatory activity.", "mechanism": "Altered expression may modulate inflammation via complement pathway.", "protein": "AMBP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346698" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "ITIH4 is a glycoprotein; glycosylation may affect anti-inflammatory properties.", "mechanism": "Increased expression in hippocampus, thalamus, cortex; modulates inflammation.", "protein": "ITIH4", "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "Glycosylation may regulate ITIH4's stability and function.", "mechanism": "Elevated in early ALS; anti-inflammatory and protease-inhibitory functions.", "protein": "ITIH4", "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "high", "disease": "Huntington's Disease", "glycan_involvement": "CFH is a glycoprotein; glycosylation modulates complement regulatory activity.", "mechanism": "Elevated in HD serum; regulates complement activation and neuroinflammation.", "protein": "CFH", "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "medium", "disease": "Huntington's Disease", "glycan_involvement": "THBS1 is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "Potential diagnostic marker; involved in cell-matrix interactions and inflammation.", "protein": "THBS1", "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "medium", "disease": "Huntington's Disease", "glycan_involvement": "MASP1 is a glycoprotein; glycosylation may affect enzymatic activity.", "mechanism": "Activates lectin pathway of complement, contributing to neuroinflammation.", "protein": "MASP1", "protein_enriched": { "function": "Membrane-anchored forms may play a role in cellular adhesion", "gene_name": "MSLN", "glycan_count": 31, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G23505EP", "G37881RL", "G39595FH", "G45395BF", "G56784JY", "G90382BL", "G02030ZB", "G13694XX", "G22310AV", "G37399XV", "G38663NM", "G47748JZ", "G48414YA", "G51640FO", "G72667IM", "G80920RR", "G82463GQ", "G84452RH", "G91473PK", "G12793SR", "G25418HZ", "G27058EU", "G30740WO", "G33791AF", "G47518TP", "G52527GH", "G55412XP", "G57888GL", "G82830MN", "G41247ZX", "G49108TO" ], "uniprot_id": "Q13421" }, "relationship_type": "causal", "source_pmcid": "PMC12346698" }, { "confidence": "high", "disease": "Huntington's Disease", "glycan_involvement": "C5 is a glycoprotein; glycosylation influences complement activation.", "mechanism": "Promotes membrane attack and inflammation in HD brain.", "protein": "C5", "relationship_type": "causal", "source_pmcid": "PMC12346698" }, { "confidence": "high", "disease": "Huntington's Disease", "glycan_involvement": "Not glycosylated.", "mechanism": "Decreased in asymptomatic HD; reflects early cytoskeletal disruption.", "protein": "CAP1", "protein_enriched": { "function": "Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity", "gene_name": "CAP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q01518" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "high", "disease": "Huntington's Disease", "glycan_involvement": "Not glycosylated.", "mechanism": "Consistently increased in HD; regulates actin cytoskeleton, linked to neuronal dysfunction.", "protein": "CAPZB", "protein_enriched": { "function": "F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping prot", "gene_name": "CAPZB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47756" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346698" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation critical for cell adhesion and sEV targeting specificity.", "mechanism": "Used to immunocapture neuron-derived sEVs carrying AD biomarkers (A\u03b2, tau) from plasma/CSF.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates sEV membrane fusion and uptake.", "mechanism": "Astrocyte-derived sEVs with CD63-rich surface enhance neuronal uptake of toxic A\u03b2, increasing neurotoxicity.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "causal", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Oligodendrocyte-derived sEVs carry MOG peptides, priming autoreactive T cells and contributing to CNS autoimmunity.", "protein": "MOG", "relationship_type": "causal", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation influences myelin stability and immune response.", "mechanism": "PLP in sEVs presented to APCs, promoting peripheral immune activation and demyelination.", "protein": "PLP", "relationship_type": "causal", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates synaptic vesicle trafficking.", "mechanism": "Reduced levels in BEVs track synaptic loss and cognitive decline in AD.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Traumatic Brain Injury", "glycan_involvement": "Glycosylation affects stability and detection in biofluids.", "mechanism": "sEV-associated GFAP correlates with TBI severity and CT-positive lesions.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346766" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation regulates cell adhesion and migration.", "mechanism": "Elevated plasma sEV CD44 during active demyelination predicts lesion formation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "MBP peptides in sEVs presented to immune cells, driving autoimmunity and demyelination.", "protein": "MBP", "relationship_type": "causal", "source_pmcid": "PMC12346766" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Polysialylation regulates cell-cell interactions and sEV targeting.", "mechanism": "NCAM-1-enriched neuronal sEVs used for CNS-specific biomarker isolation in AD.", "protein": "NCAM-1", "relationship_type": "biomarker", "source_pmcid": "PMC12346766" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation may affect aggregation and sEV loading.", "mechanism": "\u03b1-synuclein-loaded sEVs propagate pathology from gut to brain via vagus nerve.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC12346766" }, { "confidence": "medium", "disease": "Impaired myelination", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation is essential for myelin stability.", "mechanism": "MAG marks mature oligodendrocytes; unchanged MAG suggests myelination is not overtly disrupted at P28 after hyperoxia.", "protein": "MAG (Myelin-associated glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12346826" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "ICAM-1 is heavily N-glycosylated; glycosylation modulates leukocyte binding.", "mechanism": "Upregulated ICAM-1 indicates endothelial activation, promoting leukocyte adhesion and increased BBB permeability.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346826" }, { "confidence": "high", "disease": "Impaired myelination", "glycan_involvement": "NG2 is a chondroitin sulfate proteoglycan; glycosaminoglycan chains regulate cell interactions.", "mechanism": "NG2 marks immature oligodendrocytes; reduced NG2 pool after hyperoxia may impair remyelination capacity.", "protein": "NG2 (CSPG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346826" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "VEGF-A is N-glycosylated; glycosylation affects receptor binding and angiogenic activity.", "mechanism": "VEGF-A upregulation drives angiogenesis and formation of leaky vessels, contributing to BBB permeability.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12346826" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Nrp-1 is N-glycosylated; glycosylation modulates ligand binding.", "mechanism": "Nrp-1 upregulation promotes vascular sprouting and immature vessel formation.", "protein": "Nrp-1", "relationship_type": "causal", "source_pmcid": "PMC12346826" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "YM1/2 are glycoproteins; glycosylation may affect stability and immune modulation.", "mechanism": "YM1/2 downregulation reflects reduced anti-inflammatory (M2) microglial response after hyperoxia.", "protein": "YM1/2", "relationship_type": "biomarker", "source_pmcid": "PMC12346826" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation of ICAM-1 is critical for leukocyte interaction.", "mechanism": "ICAM-1 facilitates leukocyte transmigration into the brain, exacerbating neuroinflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12346826" }, { "confidence": "medium", "disease": "Brain injury", "glycan_involvement": "MAG glycosylation mediates axon-glia interactions.", "mechanism": "MAG levels indicate mature oligodendrocyte status; unchanged after hyperoxia suggests resilience to injury at this stage.", "protein": "MAG", "relationship_type": "biomarker", "source_pmcid": "PMC12346826" }, { "confidence": "medium", "disease": "Brain injury", "glycan_involvement": "Proteoglycan glycosylation affects cell migration and repair.", "mechanism": "Altered NG2 expression reflects changes in oligodendrocyte precursor pool after injury.", "protein": "NG2", "relationship_type": "biomarker", "source_pmcid": "PMC12346826" }, { "confidence": "medium", "disease": "Neurodevelopmental deficits", "glycan_involvement": "N-glycosylation modulates VEGF-A activity.", "mechanism": "VEGF-A-driven vascular changes may impair neurogenesis and neural maturation.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12346826" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "RAGE is a glycoprotein receptor for AGEs; glycosylation affects ligand binding", "mechanism": "SW inhibits AGE-RAGE interaction, reducing oxidative stress and inflammation in kidney cells", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "BSEP glycosylation is essential for membrane localization and function", "mechanism": "SW upregulates BSEP expression, promoting bile acid excretion and alleviating cholestasis", "protein": "BSEP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "MRP2 glycosylation required for stability and trafficking", "mechanism": "SW increases MRP2 expression, enhancing bile acid and toxin efflux", "protein": "MRP2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AGP glycosylation modulates ligand binding and immune response", "mechanism": "SW binds AGP, potentially modulating drug distribution and tumor cell apoptosis", "protein": "AGP", "relationship_type": "biomarker", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "GLUT4 glycosylation affects trafficking to plasma membrane", "mechanism": "SW upregulates GLUT4 expression, enhancing glucose uptake in insulin-sensitive tissues", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "NTCP glycosylation required for function", "mechanism": "SW modulates NTCP expression, improving bile acid uptake and homeostasis", "protein": "NTCP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "VEGF glycosylation modulates secretion and receptor binding", "mechanism": "SW downregulates VEGF, reducing angiogenesis and prostatic hyperplasia", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "E-cadherin glycosylation affects cell adhesion and EMT", "mechanism": "SW upregulates E-cadherin, inhibiting EMT and fibrosis in prostate tissue", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12346835" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome with insulin resistance (PCOS-IR)", "glycan_involvement": "INSR glycosylation required for receptor function", "mechanism": "SW restores INSR signaling, improving insulin sensitivity in granulosa cells", "protein": "Insulin receptor (INSR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "low", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "MRP3 glycosylation important for membrane localization", "mechanism": "SW upregulates MRP3, facilitating bile acid efflux and reducing hepatic injury", "protein": "MRP3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346835" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "ZO-1 is glycosylated, which affects tight junction stability.", "mechanism": "ZO-1 loss indicates intestinal barrier disruption in IBD; restoration correlates with mucosal healing.", "protein": "Zonula occludens-1 (ZO-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346856" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "TNF-\u03b1 is glycosylated, influencing secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 drives inflammation; reduction by EA nanoparticles alleviates colitis.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346856" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting stability and activity.", "mechanism": "IL-1\u03b2 upregulation marks active inflammation; EA nanoparticles reduce IL-1\u03b2 levels.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346856" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "IL-4 glycosylation modulates receptor interaction.", "mechanism": "IL-4 upregulation by EA nanoparticles promotes anti-inflammatory response.", "protein": "Interleukin-4 (IL-4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12346856" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "IL-10 glycosylation affects secretion and activity.", "mechanism": "IL-10 upregulation by EA nanoparticles enhances anti-inflammatory signaling.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12346856" }, { "confidence": "medium", "disease": "Colitis (DSS-induced)", "glycan_involvement": "MPO is glycosylated, influencing enzyme stability.", "mechanism": "MPO elevation reflects neutrophil infiltration; EA nanoparticles reduce MPO activity.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346856" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "SOD glycosylation affects enzyme activity.", "mechanism": "SOD activity is increased by EA nanoparticles, counteracting oxidative stress.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12346856" }, { "confidence": "high", "disease": "Colitis (DSS-induced)", "glycan_involvement": "Glycosylation stabilizes ZO-1 at tight junctions.", "mechanism": "ZO-1 restoration by EA nanoparticles indicates improved epithelial barrier in colitis.", "protein": "Zonula occludens-1 (ZO-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346856" }, { "confidence": "high", "disease": "Colitis (DSS-induced)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 function.", "mechanism": "TNF-\u03b1 reduction by EA nanoparticles mitigates DSS-induced colitis.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346856" }, { "confidence": "medium", "disease": "Colitis (DSS-induced)", "glycan_involvement": "Glycosylation affects IL-10 stability.", "mechanism": "IL-10 upregulation by EA nanoparticles supports mucosal healing in colitis.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12346856" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation is essential for MDR1 membrane localization and function.", "mechanism": "MDR1 overexpression promotes drug efflux, leading to Adriamycin resistance in TNBC cells.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Potential glycosylation may affect membrane localization; not directly studied here.", "mechanism": "ER\u03b136 activation upregulates MDR1 via non-genomic signaling, increasing drug resistance.", "protein": "Estrogen receptor alpha 36 (ER\u03b136)", "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "high", "disease": "Multidrug resistance (MDR)", "glycan_involvement": "N-glycosylation required for MDR1 stability and activity.", "mechanism": "MDR1 expression is a marker for MDR phenotype in breast cancer cells.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346883" }, { "confidence": "high", "disease": "Multidrug resistance (MDR)", "glycan_involvement": "Glycosylation may influence receptor function; not directly addressed.", "mechanism": "ER\u03b136 knockdown reduces MDR1 expression and drug resistance, suggesting therapeutic potential.", "protein": "Estrogen receptor alpha 36 (ER\u03b136)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346883" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "EGFR glycosylation is critical for ligand binding and signaling.", "mechanism": "EGFR activation by ER\u03b136 signaling promotes MDR1 expression and drug resistance.", "protein": "Epidermal growth factor receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Src activation downstream of ER\u03b136/EGFR enhances MDR1 expression.", "protein": "c-Src", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "NF-\u03baB activation increases MDR1 transcription, contributing to drug resistance.", "protein": "NF-\u03baB p65 (RelA)", "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "CREB phosphorylation enhances MDR1 transcription and drug resistance.", "protein": "CREB", "protein_enriched": { "function": "Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity", "gene_name": "CREB1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "P16220" }, "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "\u03b2-catenin activation via Wnt pathway upregulates MDR1 expression.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC12346883" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects MDR1 drug efflux capacity.", "mechanism": "MDR1 expression correlates with poor response to chemotherapy in breast cancer.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346883" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Drug is a glycoprotein; glycosylation may affect pharmacokinetics.", "mechanism": "Direct oral anticoagulant inhibiting Factor Xa to prevent thromboembolism in AF.", "protein": "Apixaban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Drug is a glycoprotein; glycosylation may affect drug transport and metabolism.", "mechanism": "Direct oral anticoagulant inhibiting Factor Xa, preferred in elderly and CKD patients.", "protein": "Edoxaban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Drug is a glycoprotein; glycosylation may affect absorption and clearance.", "mechanism": "Direct oral anticoagulant inhibiting Factor Xa, used for stroke prevention in AF.", "protein": "Rivaroxaban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Drug is a glycoprotein; glycosylation may influence bioavailability.", "mechanism": "Direct thrombin inhibitor, used for stroke prevention in AF.", "protein": "Dabigatran", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "These clotting factors are glycoproteins; glycosylation is essential for their secretion and function.", "mechanism": "Targeted by VKAs to reduce clotting and prevent stroke in AF.", "protein": "Vitamin K-dependent clotting factors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346891" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation regulates transporter activity and drug interactions.", "mechanism": "Transports DOACs; inhibitors require dose adjustment to avoid toxicity.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346891" }, { "confidence": "medium", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation may affect drug clearance and bleeding risk.", "mechanism": "Incorrect dosing or impaired renal function increases bleeding risk.", "protein": "Apixaban", "relationship_type": "causal", "source_pmcid": "PMC12346891" }, { "confidence": "medium", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation may affect renal excretion and bleeding risk.", "mechanism": "Dose adjustment in CKD reduces major bleeding risk.", "protein": "Edoxaban", "relationship_type": "causal", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation may affect renal handling of drug.", "mechanism": "Preferred DOAC due to lower bleeding risk in CKD patients.", "protein": "Apixaban", "relationship_type": "protective", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation may affect renal handling of drug.", "mechanism": "Preferred DOAC due to lower bleeding risk in CKD patients.", "protein": "Edoxaban", "relationship_type": "protective", "source_pmcid": "PMC12346891" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "LC3B is known to be post-translationally modified, but glycosylation not directly discussed in this article", "mechanism": "LC3B expression reflects autophagic flux; decreased in PD models, restored by berberine", "protein": "LC3B", "protein_enriched": { "function": "Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes) (PubMed:20418806, PubMed:23209295, PubMed:28017329). Plays a role in mitophagy which contributes to regulate m", "gene_name": "MAP1LC3B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9GZQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346907" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "p62 is a glycoprotein; glycosylation status not directly discussed in this article", "mechanism": "p62 accumulation indicates impaired autophagy; berberine normalizes p62 levels in PD models", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346907" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SIRT1 is glycosylated; glycan involvement not directly addressed in this study", "mechanism": "SIRT1 regulates mitochondrial function and autophagy; berberine upregulates SIRT1, conferring neuroprotection", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346907" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "PGC-1\u03b1 is glycosylated; glycan involvement not directly addressed in this study", "mechanism": "PGC-1\u03b1 promotes mitochondrial biogenesis; berberine increases PGC-1\u03b1, improving mitochondrial health in PD", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346907" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "AMPK is glycosylated; glycan involvement not directly addressed in this study", "mechanism": "AMPK activation restores energy homeostasis and autophagy; berberine activates AMPK in PD models", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346907" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Alpha-synuclein can be glycosylated; glycan involvement not directly addressed in this study", "mechanism": "Alpha-synuclein aggregation is pathogenic in PD; autophagy impairment leads to its accumulation", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC12346907" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (general)", "glycan_involvement": "General glycosylation known, not discussed here", "mechanism": "LC3B is a marker of autophagic activity, relevant in multiple neurodegenerative diseases", "protein": "LC3B", "protein_enriched": { "function": "Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes) (PubMed:20418806, PubMed:23209295, PubMed:28017329). Plays a role in mitophagy which contributes to regulate m", "gene_name": "MAP1LC3B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9GZQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346907" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (general)", "glycan_involvement": "General glycosylation known, not discussed here", "mechanism": "p62 accumulation is a hallmark of autophagy impairment in neurodegeneration", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346907" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (general)", "glycan_involvement": "General glycosylation known, not discussed here", "mechanism": "SIRT1 activation is neuroprotective across neurodegenerative diseases", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346907" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (general)", "glycan_involvement": "General glycosylation known, not discussed here", "mechanism": "PGC-1\u03b1 supports mitochondrial health in neurodegeneration", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346907" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "ICAM-1 is a heavily N-glycosylated glycoprotein; glycosylation modulates its adhesive function.", "mechanism": "Upregulated by NETs, promotes neutrophil adhesion and endothelial barrier disruption, leading to vascular leakage.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "VCAM-1 glycosylation affects ligand binding and cell signaling.", "mechanism": "NETs induce VCAM-1 expression, enhancing leukocyte adhesion and endothelial activation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "vWF is extensively glycosylated; glycosylation regulates multimerization and platelet binding.", "mechanism": "NETs and platelet activation increase vWF release, promoting microthrombi formation in DIC.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "PF4 is glycosylated; glycosylation may affect its interaction with NETs and heparin.", "mechanism": "PF4 released by platelets facilitates NET formation and immunothrombosis.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "MPO is glycosylated; glycosylation influences its stability and activity.", "mechanism": "MPO-DNA complexes are elevated in sepsis, correlating with disease severity and organ damage.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346910" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "ELANE glycosylation may modulate its proteolytic activity.", "mechanism": "NE-DNA complexes indicate NET formation and are associated with organ injury in sepsis.", "protein": "Neutrophil Elastase (ELANE)", "relationship_type": "biomarker", "source_pmcid": "PMC12346910" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "HMGB1 is not classically glycosylated but can interact with glycosaminoglycans.", "mechanism": "Lactylated HMGB1 links NET activity to AKI, promoting inflammation and tissue damage.", "protein": "High Mobility Group Box 1 (HMGB1)", "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "medium", "disease": "Thrombotic Microangiopathies", "glycan_involvement": "S100A8/A9 can bind glycosaminoglycans; not classically glycosylated.", "mechanism": "Released during NETosis, reflects disease activity and inflammation.", "protein": "S100A8/A9 (Calprotectin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "HBP interacts with glycosaminoglycans on endothelium.", "mechanism": "HBP binds endothelial proteoglycans, increasing vascular permeability and leakage.", "protein": "Heparin-binding protein (HBP)", "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "TM is N-glycosylated; glycosylation is essential for anticoagulant function.", "mechanism": "NET-derived histones inhibit TM-mediated protein C activation, promoting coagulopathy.", "protein": "Thrombomodulin (TM)", "protein_enriched": { "function": "Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis (PubMed:10761923). Ac", "gene_name": "THBD", "glycan_count": 2, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G45395BF", "G92135MA" ], "uniprot_id": "P07204" }, "relationship_type": "causal", "source_pmcid": "PMC12346910" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "O-glycosylation and sialylation required for selectin binding.", "mechanism": "PSGL-1 mediates MM cell adhesion, homing, survival, and drug resistance via binding to P-selectin and E-selectin.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Recognizes sialylated glycan ligands on MM cells (e.g., sialylated PSGL-1).", "mechanism": "E-selectin on BMECs supports MM cell homing and bone metastasis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Binds O-glycosylated, sialylated PSGL-1 on MM cells.", "mechanism": "P-selectin on BMECs/BMSCs facilitates MM\u2013platelet interactions, aiding immune evasion and metastasis.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation required for VCAM-1 function and integrin binding.", "mechanism": "VCAM-1 binds MM integrins (VLA-4), CD44, and CD56, promoting adhesion, proliferation, and resistance to apoptosis.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346918" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation modulates ligand binding.", "mechanism": "ICAM-1 on BMSCs interacts with MM cell LFA-1, supporting retention and drug resistance.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Sialylation of integrin subunits increases binding affinity.", "mechanism": "Sialylated \u03b14\u03b21 enhances MM cell adhesion to VCAM-1, promoting homing and survival.", "protein": "Integrin \u03b14\u03b21 (VLA-4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Sialylation enhances ligand binding.", "mechanism": "Sialylated \u03b14\u03b27 interacts with MadCAM-1, aiding MM cell retention in bone marrow.", "protein": "Integrin \u03b14\u03b27", "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation required for ligand binding and function.", "mechanism": "CD147 on MM cells binds Cyclophilin A, promoting homing, proliferation, and drug resistance.", "protein": "CD147", "protein_enriched": { "function": "Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photor", "gene_name": "BSG", "glycan_count": 62, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G49108TO", "G01160VV", "G02815KT", "G05049YU", "G08918WF", "G10488MI", "G15127JD", "G15664MX", "G23719VF", "G27058EU", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G50856PC", "G53075ES", "G57776ZS", "G59626AS", "G62765YT", "G65414LI", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G74381CZ", "G77330BQ", "G79666IR", "G80075MS", "G80920RR", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G29068FM", "G43417UB", "G05724UK", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G20210JR", "G20528HD", "G23294PN", "G28681TP", "G32788FZ", "G35541EV", "G46275YY", "G47644PP", "G49755GI", "G60967DT", "G64527OM", "G70101JE", "G70619PT", "G80479JV", "G83460ZZ", "G85269DF", "G92062TF", "G93718GY", "G50713DU" ], "uniprot_id": "P35613" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Catalyzes sialylation of O-glycans on selectin ligands.", "mechanism": "Overexpression of ST3Gal-6 enhances sialylation of selectin ligands, increasing MM homing to bone marrow.", "protein": "ST3Gal-6", "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "MadCAM-1 on BMECs interacts with sialylated integrin \u03b14\u03b27, supporting MM cell retention.", "protein": "MadCAM-1", "protein_enriched": { "function": "Cell adhesion leukocyte receptor expressed by mucosal venules, helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and the intestinal lamina propria. It can bind both i", "gene_name": "MADCAM1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q13477" }, "relationship_type": "causal", "source_pmcid": "PMC12346918" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation of GLP-1 receptor affects ligand binding and receptor stability.", "mechanism": "Semaglutide activates GLP-1 receptor, enhancing insulin secretion and improving glycemic control.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346962" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Semaglutide is a glycopeptide analog; glycosylation increases stability and half-life.", "mechanism": "Semaglutide reduces body weight and fat mass via GLP-1 receptor activation, increasing satiety.", "protein": "Semaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346962" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Insulin glycosylation affects secretion and receptor interaction.", "mechanism": "Insulin secretion is impaired in T2D; semaglutide enhances glucose-dependent insulin secretion.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Albumin glycosylation status can change in renal disease.", "mechanism": "Albuminuria is a marker of renal damage; improved metabolic control reduces albuminuria.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL receptor glycosylation modulates LDL binding and clearance.", "mechanism": "Improved metabolic control via semaglutide reduces LDL cholesterol, impacting CVD risk.", "protein": "LDL receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "GLP-1 glycosylation affects peptide stability and receptor interaction.", "mechanism": "GLP-1 signaling reduces inflammation and improves CV outcomes.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "SGLT2 glycosylation affects membrane localization and function.", "mechanism": "SGLT2 inhibitors reduce glucose reabsorption; used in combination with GLP-1 RAs.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates fibrinogen function and inflammatory response.", "mechanism": "Elevated fibrinogen is linked to inflammation and atherosclerosis risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation of IgG modulates immune response and inflammation.", "mechanism": "Altered IgG glycosylation in obesity reflects chronic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346962" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation changes in transferrin reflect hepatic metabolic status.", "mechanism": "Altered transferrin glycosylation is associated with liver dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346962" }, { "confidence": "high", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation modulates adhesion molecule function and neutrophil binding.", "mechanism": "Upregulation leads to neutrophil recruitment and endothelial injury, promoting erosion.", "protein": "Endothelial cell adhesion molecules", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Plaque erosion (PE)", "glycan_involvement": "TLR2 glycosylation affects ligand recognition and signaling.", "mechanism": "TLR2 activation in endothelial cells triggers low-grade inflammation and endothelial desquamation.", "protein": "Toll-like receptor 2 (TLR2)", "protein_enriched": { "function": "Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bac", "gene_name": "TLR2", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G08146BT", "G22310AV", "G71146HJ", "G75983OB", "G00912UN", "G25451PN", "G27058EU", "G40926MX", "G45395BF", "G45495MK", "G62765YT", "G70101JE", "G80920RR", "G83229XP", "G84452RH", "G83460ZZ" ], "uniprot_id": "O60603" }, "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "medium", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation is critical for junctional protein stability and function.", "mechanism": "Loss/disruption of junctional proteins impairs endothelial barrier, facilitating erosion.", "protein": "Intercellular junctional proteins", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Plaque erosion (PE)", "glycan_involvement": "NET proteins are glycosylated, influencing their stability and prothrombotic activity.", "mechanism": "NETs promote local thrombosis and further endothelial injury.", "protein": "Neutrophil extracellular trap (NET) proteins", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation regulates MMP9 secretion and activity.", "mechanism": "Neutrophil-derived MMP9 intensifies endothelial detachment and cell death.", "protein": "Matrix metalloproteinase 9 (MMP9)", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Plaque rupture (PR)", "glycan_involvement": "IL-6 glycosylation affects secretion and receptor binding.", "mechanism": "Elevated IL-6 reflects systemic inflammation in PR-ACS.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Plaque rupture (PR)", "glycan_involvement": "Glycosylation modulates IL-1\u03b2 activity.", "mechanism": "High IL-1\u03b2 levels drive inflammatory degradation of fibrous cap.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC12346965" }, { "confidence": "medium", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation influences granzyme secretion and cytotoxicity.", "mechanism": "CD8+ T cell-derived granzyme A mediates endothelial damage in PE.", "protein": "Granzyme A", "protein_enriched": { "function": "Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubM", "gene_name": "GZMA", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G37995HC", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G92275SC" ], "uniprot_id": "P12544" }, "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "medium", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation required for perforin stability and function.", "mechanism": "Perforin from cytotoxic T cells contributes to endothelial injury.", "protein": "Perforin", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "medium", "disease": "Plaque erosion (PE)", "glycan_involvement": "Glycosylation of binding proteins modulates interaction with hyaluronic acid.", "mechanism": "Elevated hyaluronic acid stimulates TLR2-mediated neutrophil activation.", "protein": "Hyaluronic acid binding proteins", "relationship_type": "causal", "source_pmcid": "PMC12346965" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "AOPPs are formed from glycoproteins (mainly albumin) via oxidative stress; glycosylation status may affect susceptibility.", "mechanism": "AOPPs are elevated in adolescents with higher cardiovascular risk scores, reflecting increased oxidative modification of plasma proteins.", "protein": "Advanced Oxidation Protein Products (AOPPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL is N-glycosylated; glycan modifications influence susceptibility to oxidation and uptake by macrophages.", "mechanism": "Oxidative modification of LDL (including glycoprotein moieties) promotes cholesterol accumulation and inflammation in vessel walls.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "HDL glycosylation affects its function and catabolism; small HDL particles (with altered glycosylation) are rapidly cleared.", "mechanism": "Lower HDL-c levels are associated with higher CVD risk; HDL glycoproteins have antioxidant and anti-inflammatory roles.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "SOD can be glycosylated, which may affect stability and activity.", "mechanism": "SOD is an antioxidant enzyme; its activity reflects antioxidant defense status in CVD risk stratification.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "MDA can modify glycoproteins, potentially altering their function and immunogenicity.", "mechanism": "MDA adducts are increased in high CVD risk adolescents, indicating lipid peroxidation and protein modification.", "protein": "Malondialdehyde-modified proteins (MDA adducts)", "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Subclinical Atherosclerosis", "glycan_involvement": "Oxidative modification of glycoproteins contributes to AOPP formation.", "mechanism": "AOPPs are associated with early vascular changes before clinical CVD manifests.", "protein": "Advanced Oxidation Protein Products (AOPPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Subclinical Atherosclerosis", "glycan_involvement": "Glycosylation modulates LDL oxidation and immune recognition.", "mechanism": "Oxidized LDL initiates foam cell formation and vascular inflammation.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Obesity alters HDL glycosylation, impacting its anti-atherogenic properties.", "mechanism": "Obesity in adolescents is associated with lower HDL-c and altered HDL glycoprotein composition.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycoprotein oxidation impairs endothelial cell signaling.", "mechanism": "AOPPs contribute to endothelial dysfunction by promoting oxidative stress and inflammation.", "protein": "Advanced Oxidation Protein Products (AOPPs)", "relationship_type": "causal", "source_pmcid": "PMC12346967" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "MDA modification of glycoproteins may enhance their atherogenicity.", "mechanism": "MDA adducts reflect ongoing lipid and protein oxidation in atherosclerotic processes.", "protein": "Malondialdehyde-modified proteins (MDA adducts)", "relationship_type": "biomarker", "source_pmcid": "PMC12346967" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation affects receptor conformation and ligand binding.", "mechanism": "Mediates platelet adhesion and aggregation at sites of vascular injury, promoting arterial thrombosis and plaque progression.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12346972" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation modulates receptor function and drug binding.", "mechanism": "Targeted by antiplatelet drugs to inhibit ADP-induced platelet activation and aggregation, reducing thrombotic events.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346972" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation critical for multimerization and platelet binding.", "mechanism": "Facilitates platelet adhesion to subendothelial collagen, initiating thrombus formation and contributing to plaque development.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12346972" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation required for receptor activation and fibrinogen binding.", "mechanism": "Platelet aggregation via IIb/IIIa leads to arterial occlusion and myocardial infarction.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation influences receptor surface expression.", "mechanism": "Inhibition reduces risk of thrombotic stroke by decreasing platelet activation.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Peripheral artery disease", "glycan_involvement": "Glycosylation state affects plasma levels and activity.", "mechanism": "Elevated levels indicate increased platelet activation and vascular injury.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation modulates receptor cleavage and signaling.", "mechanism": "Activation promotes platelet aggregation and vascular inflammation.", "protein": "Thrombin receptor (PAR-1)", "protein_enriched": { "function": "High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores (PubMed:1672265, PubMed:8136362). The thrombin-activated receptor signaling pathway is me", "gene_name": "F2R", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G62765YT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P25116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects receptor trafficking.", "mechanism": "Initiates platelet shape change and transient activation, contributing to early thrombus formation.", "protein": "P2Y1 receptor", "protein_enriched": { "function": "Receptor for extracellular adenine nucleotides such as ADP (PubMed:25822790, PubMed:9038354, PubMed:9442040). In platelets, binding to ADP leads to mobilization of intracellular calcium ions via activ", "gene_name": "P2RY1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P47900" }, "relationship_type": "causal", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "Platelet aggregation via IIb/IIIa contributes to cerebral arterial occlusion.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12346972" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects activity and clearance.", "mechanism": "High plasma levels correlate with increased risk of myocardial infarction.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12346972" }, { "confidence": "high", "disease": "Gastric adenocarcinoma", "glycan_involvement": "Ceruloplasmin is a copper-containing glycoprotein; glycosylation required for stability and function.", "mechanism": "Elevated at all stages; indicates involvement of iron metabolism and antioxidant defense in pathogenesis.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346977" }, { "confidence": "high", "disease": "Gastric adenocarcinoma", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Increased in early stages, decreased in stage IV; involved in inflammation, apoptosis, and tumor progression.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346977" }, { "confidence": "high", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IL-6 glycosylation modulates stability and receptor interaction.", "mechanism": "Elevated in all stages; promotes tumor cell migration, angiogenesis, and immune modulation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346977" }, { "confidence": "high", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IL-8 glycosylation affects chemotactic activity.", "mechanism": "Increased in early stages, decreased in stage IV; promotes tumor cell migration and inflammation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IL-10 glycosylation required for secretion and activity.", "mechanism": "Elevated in all stages; anti-inflammatory, antagonizes pro-inflammatory cytokines, may suppress anti-tumor immunity.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IL-4 glycosylation affects receptor binding and stability.", "mechanism": "Increased in early stages, decreased in stage IV; involved in Th2 immune response.", "protein": "IL-4", "relationship_type": "biomarker", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IFN\u03b3 glycosylation modulates activity and secretion.", "mechanism": "Decreased in early stages, increased in stage IV; key in Th1 response and macrophage activation.", "protein": "IFN\u03b3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "TNF-\u03b2 glycosylation affects stability and function.", "mechanism": "Increased in early stages, decreased in stage IV; involved in inflammation and immune regulation.", "protein": "TNF-\u03b2", "protein_enriched": { "function": "Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (PubMed:9462508). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR (PubMed:24248355). Lymphoto", "gene_name": "LTA", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23863VK", "G29228MX", "G45359RY", "G52038JM", "G63889NK", "G72797UR", "G78059CC", "G86357DX", "G90093AU", "G91636VS" ], "uniprot_id": "P01374" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "IL-17A glycosylation influences secretion and activity.", "mechanism": "Elevated in all stages; promotes inflammation and tumor progression via Th17 pathway.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346977" }, { "confidence": "medium", "disease": "Gastric adenocarcinoma", "glycan_involvement": "Glycosylation required for enzyme stability and activity.", "mechanism": "Increased activity at all stages; neutralizes lipid peroxidation products, protects cells from oxidative damage.", "protein": "Glutathione peroxidase", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such ", "gene_name": "GPX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07203" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12346977" }, { "confidence": "high", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "N-glycosylation affects NT-proBNP stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and dysfunction; levels decrease with improved cardiac function.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "high", "disease": "Platelet Aggregation Disorders", "glycan_involvement": "N-glycosylation modulates sP-Selectin's adhesive properties.", "mechanism": "sP-Selectin indicates platelet activation and aggregation; reduced levels reflect decreased platelet activation.", "protein": "sP-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "high", "disease": "Platelet Aggregation Disorders", "glycan_involvement": "Glycosylation influences Gp-VI surface expression and function.", "mechanism": "Gp-VI mediates platelet-collagen interactions; decreased levels indicate reduced platelet activation.", "protein": "Gp-VI (Glycoprotein VI)", "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation affects CRP's solubility and receptor interactions.", "mechanism": "hs-CRP is an acute phase reactant; elevated in systemic inflammation and cardiovascular risk.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation may affect Nox-2 localization and activity.", "mechanism": "Nox-2 generates reactive oxygen species; elevated in oxidative stress conditions.", "protein": "Nox-2", "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation influences insulin receptor binding and clearance.", "mechanism": "Insulin resistance impairs glucose uptake; improved sensitivity with EAA supplementation.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation modulates IGF-1 receptor interactions.", "mechanism": "IGF-1 promotes muscle protein synthesis and growth; anabolic effects counteract sarcopenia.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "N-glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Neprilysin degrades natriuretic peptides; inhibition improves cardiac function.", "protein": "Sacubitril/Valsartan target (Neprilysin)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects SGLT2 trafficking and function.", "mechanism": "SGLT2 mediates renal glucose reabsorption; inhibition improves glycemic control.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12346981" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "N-glycosylation influences NT-proBNP half-life and detection.", "mechanism": "Elevated NT-proBNP is associated with frailty and poor prognosis in elderly patients.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346981" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "N-glycosylation affects albumin stability and serum half-life.", "mechanism": "Serum albumin levels reflect liver synthetic function and are used in risk scores (ALBI, Child\u2013Pugh, MELD) to predict PHLF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "Albumin glycosylation influences bilirubin binding and transport.", "mechanism": "Serum bilirubin, often measured as part of ALBI and Child\u2013Pugh scores, indicates hepatic excretory function and risk for PHLF.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "ICG binds to plasma glycoproteins for hepatic uptake and excretion.", "mechanism": "ICG clearance rate is a direct measure of hepatic function and predicts risk of PHLF.", "protein": "Indocyanine Green (ICG) Clearance Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates binding and clearance of hyaluronic acid.", "mechanism": "Serum hyaluronic acid levels reflect extracellular matrix turnover and fibrosis severity.", "protein": "Hyaluronic Acid Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "N-glycosylation is essential for PT secretion and activity.", "mechanism": "PT activity is used in '50\u201350 criteria' and MELD score to assess coagulation and liver synthetic function.", "protein": "Prothrombin (PT)", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation affects platelet glycoprotein function and clearance.", "mechanism": "Platelet count is reduced in cirrhosis due to splenic sequestration and is used in APRI and MELD scores.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "medium", "disease": "Chronic hepatitis", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Elevated AST reflects hepatocyte injury and is used in APRI and MELD scores.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of albumin and bilirubin-binding proteins affects score accuracy.", "mechanism": "ALBI score predicts liver function and surgical risk in HCC patients.", "protein": "ALBI (Albumin-Bilirubin Index)", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation status influences marker levels and function.", "mechanism": "Child\u2013Pugh score uses glycoprotein markers (albumin, bilirubin, PT) to stage cirrhosis and predict outcomes.", "protein": "Child\u2013Pugh Glycoprotein Markers", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "Glycosylation affects protein stability and serum measurements.", "mechanism": "MELD score integrates glycoprotein-based lab values to predict risk of PHLF and mortality.", "protein": "MELD Glycoprotein Markers", "relationship_type": "biomarker", "source_pmcid": "PMC12347032" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered glycosylation may affect protein stability and lipid droplet association.", "mechanism": "I148M variant (rs738409) leads to triglyceride accumulation, lipotoxicity, and oxidative DNA damage, promoting hepatocarcinogenesis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Potential impact on protein folding and lipid metabolism via glycosylation.", "mechanism": "I148M variant increases hepatic triglyceride accumulation, predisposing to NAFLD.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate extracellular matrix interactions.", "mechanism": "Loss of hydrolase activity in hepatic stellate cells leads to extracellular matrix deposition and fibrosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may regulate protein stability and metabolic activity.", "mechanism": "rs780094 variant alters lipid metabolism, increasing hepatic fat and HCC risk.", "protein": "GCKR", "protein_enriched": { "function": "Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:23621087, PubMed:23733961). Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK t", "gene_name": "GCKR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14397" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect membrane localization and enzymatic activity.", "mechanism": "rs641738 variant (Glu17Val) alters phosphatidylinositol remodeling, increasing hepatic fat and inflammation.", "protein": "MBOAT7", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZVQ5" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may influence protein folding and secretion.", "mechanism": "rs58542926 variant leads to misfolded protein, VLDL retention, steatosis, and increased HCC risk (not significant in Mexican population).", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NCAN is a proteoglycan; glycosylation critical for ECM function.", "mechanism": "rs2228603 variant associated with altered VLDL/triglyceride levels and hepatic lipid accumulation (not significant in Mexican population).", "protein": "NCAN", "protein_enriched": { "function": "Cell adhesion protein that is required for normal responses to cell-cell contacts in brain and in the peripheral nervous system. Plays a role in neurite outgrowth in response to contactin binding. Pla", "gene_name": "NRCAM", "glycan_count": 72, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G37399XV", "G39188ZX", "G41247ZX", "G82463GQ", "G80920RR", "G01650EU", "G06356OH", "G31665QC", "G89205CJ", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G07755XJ", "G10486CT", "G11314AS", "G11629QQ", "G18647XP", "G27058EU", "G28541PG", "G31852PQ", "G39446WN", "G42124LM", "G45395BF", "G47644PP", "G57317CE", "G57776ZU", "G59536GA", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G70619PT", "G72787SB", "G72790NZ", "G83460ZZ", "G85144OK", "G90659AW", "G92050GC", "G95865ZB", "G14796IU", "G34989PA", "G41071NU", "G63651JH", "G65225MN", "G82830MN", "G83646BJ", "G87661QW", "G72747WU", "G83633GK", "G05049YU", "G15664MX", "G54010QB", "G56770VP", "G72197KC", "G87389XI", "G43417UB", "G22310AV", "G48414YA", "G04657PL", "G08918WF", "G15169WU", "G37412TK", "G43669FQ", "G58954YZ", "G56784JY", "G08290VR", "G14972EH", "G20706XG", "G36145AL", "G43223CG", "G76295SF" ], "uniprot_id": "Q92823" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may affect inflammatory signaling.", "mechanism": "I148M variant increases risk of steatohepatitis via lipid accumulation and inflammation.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may modulate fibrotic signaling.", "mechanism": "I148M variant promotes progression from steatosis to cirrhosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Combined glycosylation changes may synergistically affect lipid handling and cell signaling.", "mechanism": "Gene-gene interaction increases cumulative risk for HCC via combined effects on hepatic lipid metabolism.", "protein": "PNPLA3 + GCKR + MBOAT7", "relationship_type": "causal (epistatic interaction)", "source_pmcid": "PMC12347070" }, { "confidence": "high", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Fc glycosylation affects antibody-dependent cellular cytotoxicity.", "mechanism": "Avelumab (anti-PD-L1 glycoprotein antibody) used in combination therapy; efficacy influenced by immune and nutritional status.", "protein": "Avelumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347088" }, { "confidence": "high", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Nivolumab (anti-PD-1 glycoprotein antibody) used in immunotherapy; baseline markers did not predict TTF in this cohort.", "protein": "Nivolumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347088" }, { "confidence": "high", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Fc glycosylation impacts antibody function.", "mechanism": "Ipilimumab (anti-CTLA-4 glycoprotein antibody) used in combination; elevated AST predicts shorter TTF.", "protein": "Ipilimumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347088" }, { "confidence": "high", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Glycosylation may affect enzyme stability and clearance.", "mechanism": "Elevated AST at baseline predicts shorter time to treatment failure with Ipilimumab + Nivolumab.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "medium", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Elevated ALT predicts shorter TTF with Cabozantinib in later lines.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "medium", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Minor glycosylation may affect hemoglobin turnover.", "mechanism": "Low hemoglobin predicts shorter TTF with Avelumab + Axitinib.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "medium", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Surface glycosylation regulates platelet function and inflammation.", "mechanism": "Elevated platelet count predicts shorter TTF with Cabozantinib.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "medium", "disease": "Metastatic Renal Cell Carcinoma (mRCC)", "glycan_involvement": "Glycosylation modulates immune cell trafficking and activation.", "mechanism": "Low lymphocyte count predicts shorter TTF with Avelumab + Axitinib.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "high", "disease": "Lymph node metastases in mRCC", "glycan_involvement": "Glycosylation of antibody may affect tissue penetration.", "mechanism": "Presence of lymph node metastases predicts poor response (shorter TTF) to Avelumab + Axitinib.", "protein": "Avelumab", "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "medium", "disease": "Liver metastases in mRCC", "glycan_involvement": "Glycosylation may influence enzyme release in hepatic injury.", "mechanism": "Elevated ALT and presence of liver metastases predict shorter TTF with Cabozantinib.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347088" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "L1CAM is a heavily glycosylated cell adhesion molecule; glycosylation affects EV sorting and stability.", "mechanism": "Elevated L1CAM+ EVs in serum reflect CNS immune activity and decrease after anti-CD20 therapy.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD79B is N-glycosylated, influencing BCR surface expression and EV incorporation.", "mechanism": "Upregulated in L1CAM+ EVs at baseline, downregulated after rituximab, reflecting B-cell activity.", "protein": "CD79B", "protein_enriched": { "function": "Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking t", "gene_name": "CD79B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P40259" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "TACI is glycosylated, modulating receptor function and ligand binding.", "mechanism": "Downregulated in serum EVs after rituximab, indicating B-cell suppression.", "protein": "TNFRSF13B (TACI)", "protein_enriched": { "function": "Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and ", "gene_name": "TNFRSF13B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O14836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CCL2 glycosylation affects chemokine gradient formation and receptor interaction.", "mechanism": "Elevated in CSF and serum L1CAM+ EVs at baseline, associated with monocyte/T-cell recruitment.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "EBNA1 is glycosylated, influencing immune recognition and EV packaging.", "mechanism": "Elevated EBNA1+ EVs in serum L1CAM+ EVs at baseline; EBV infection is a prerequisite for MS.", "protein": "EBNA1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "LAMP3 is highly glycosylated, affecting lysosomal trafficking and immune signaling.", "mechanism": "Upregulated in L1CAM+ EVs at baseline, associated with dendritic cell activation.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD24 is GPI-anchored and glycosylated, modulating immune cell interactions.", "mechanism": "Elevated in CSF total EVs at baseline, involved in B-cell activation.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Integrin glycosylation regulates cell adhesion and EV release.", "mechanism": "Elevated in serum L1CAM+ EVs at baseline, may reflect platelet activation in MS.", "protein": "CD41b (ITGA2B)", "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "GP9 glycosylation affects platelet function and EV composition.", "mechanism": "Elevated in serum L1CAM+ EVs at baseline, linked to platelet-derived EVs in MS.", "protein": "CD42a (GP9)", "protein_enriched": { "function": "The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is", "gene_name": "GP9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P14770" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "TREM2 glycosylation modulates receptor stability and immune signaling.", "mechanism": "Upregulated in CSF total EVs at baseline, associated with microglial activation.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347089" }, { "confidence": "high", "disease": "COVID-19 in pregnancy", "glycan_involvement": "Spike heavily N-glycosylated; glycosylation modulates receptor binding and immune evasion.", "mechanism": "Spike protein mediates viral entry into placental cells via ACE2, leading to infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "COVID-19 in pregnancy", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity.", "mechanism": "ACE2 serves as entry receptor for SARS-CoV-2 in placental tissue.", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Placental inflammation", "glycan_involvement": "Glycosylation shields spike from immune detection, modulating inflammation.", "mechanism": "Spike protein expression in placenta triggers local inflammatory response.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Placental inflammation", "glycan_involvement": "CD68 is a glycoprotein marker for macrophages; glycosylation required for function.", "mechanism": "Increased CD68+ macrophages indicate placental inflammatory infiltration in SARS-CoV-2 infection.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Neonatal complications (NICU stay)", "glycan_involvement": "Spike glycosylation may influence severity of placental infection.", "mechanism": "Higher spike protein expression in placenta correlates with increased NICU admission.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Chronic histiocytic intervillitis", "glycan_involvement": "CD68 glycosylation necessary for macrophage marker function.", "mechanism": "CD68+ cell infiltration in intervillous space is diagnostic for intervillitis, linked to poor perinatal outcome.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "ACE2 glycosylation may affect receptor stability and function.", "mechanism": "Placental ACE2 expression correlates with elevated maternal O2- anion levels.", "protein": "ACE2 receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Spike glycosylation may modulate oxidative stress response.", "mechanism": "Spike protein expression in placenta correlates with increased maternal TBARS (lipid peroxidation).", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "CD68 glycosylation required for marker detection.", "mechanism": "CD68+ macrophage expression in placenta correlates with maternal and fetal TBARS levels.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347127" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "ACE2 glycosylation may regulate receptor activity and vascular effects.", "mechanism": "Decreased ACE2 function is associated with preeclampsia and impaired fetal growth.", "protein": "ACE2 receptor", "relationship_type": "protective", "source_pmcid": "PMC12347127" }, { "confidence": "high", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "ITGB3 is a glycoprotein; glycosylation affects receptor function and platelet aggregation.", "mechanism": "ITGB3 rs3809865 TT genotype increases RPL risk by altering platelet aggregation and embryo implantation.", "protein": "Integrin subunit beta 3 (ITGB3)", "protein_enriched": { "function": "Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willeb", "gene_name": "ITGB3", "glycan_count": 31, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G02815KT", "G06356OH", "G26330YA", "G27058EU", "G27947YN", "G28541PG", "G31852PQ", "G41247ZX", "G45504EY", "G48414YA", "G59626AS", "G62765YT", "G80920RR", "G94470IW", "G95865ZB", "G09724ZC", "G22768VO", "G81315DD", "G08290VR", "G22573RC", "G46503DX", "G83633GK", "G87661QW", "G42227JK", "G05724UK", "G64527OM", "G70101JE", "G77547TA", "G83460ZZ", "G49108TO" ], "uniprot_id": "P05106" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347128" }, { "confidence": "high", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "FGG is glycosylated; glycosylation modulates fibrinogen stability and clot formation.", "mechanism": "FGG rs1049636 TC genotype is associated with decreased RPL risk, possibly via increased fibrinogen levels and improved placental formation.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "medium", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "PEAR1 is a glycoprotein; glycosylation may affect receptor signaling and platelet activation.", "mechanism": "PEAR1 rs12137505 GG genotype correlates with increased CD56+ NK cell counts, potentially contributing to RPL via immune dysregulation.", "protein": "PEAR1", "protein_enriched": { "function": "Involved in the mineralization and structural organization of enamel", "gene_name": "AMBN", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP70" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "medium", "disease": "Venous Thromboembolism", "glycan_involvement": "Glycosylation of FGG affects clot formation and stability.", "mechanism": "FGG rs1049636 TC genotype reduces risk of venous thromboembolism by increasing fibrinogen levels.", "protein": "FGG", "relationship_type": "protective", "source_pmcid": "PMC12347128" }, { "confidence": "medium", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "GP1BA glycosylation is critical for von Willebrand factor binding and platelet adhesion.", "mechanism": "GP1BA rs6065 C > T allele in combination with ITGB3 rs3809865 T allele increases RPL risk via altered platelet adhesion.", "protein": "GP1BA", "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "medium", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "PECAM1 glycosylation regulates cell adhesion and vascular permeability.", "mechanism": "PECAM1 rs2812 C > T genotype in combination with FGG and PEAR1 variants is associated with decreased RPL risk, possibly via modulation of vascular integrity.", "protein": "PECAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "low", "disease": "Implantation Failure", "glycan_involvement": "Glycosylation modulates PEAR1-mediated platelet activation.", "mechanism": "PEAR1 variants influence platelet counts and may affect endometrial receptivity and implantation.", "protein": "PEAR1", "protein_enriched": { "function": "Involved in the mineralization and structural organization of enamel", "gene_name": "AMBN", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP70" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects fibrinogen function in coagulation and placental attachment.", "mechanism": "Decreased fibrinogen levels (FGG) are associated with increased risk of preeclampsia.", "protein": "FGG", "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "low", "disease": "Endometriosis", "glycan_involvement": "Glycosylation modulates ITGB3-mediated cell adhesion.", "mechanism": "Platelet dysfunction (ITGB3) is implicated in abnormal bleeding and endometriosis.", "protein": "ITGB3", "relationship_type": "causal", "source_pmcid": "PMC12347128" }, { "confidence": "low", "disease": "Recurrent Pregnancy Loss (RPL)", "glycan_involvement": "Glycosylation may affect PEAR1 receptor clustering and signaling.", "mechanism": "PEAR1 rs822442 AA/rs12137505 GA genotype combination is associated with increased RPL risk.", "protein": "PEAR1", "protein_enriched": { "function": "Involved in the mineralization and structural organization of enamel", "gene_name": "AMBN", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP70" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347128" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Factor Xa is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "Inhibition of factor Xa by apixaban reduces thromboembolic risk in AF.", "protein": "Coagulation factor Xa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347149" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation modulates factor Xa activity and plasma half-life.", "mechanism": "Factor Xa inhibition prevents clot formation in VTE.", "protein": "Coagulation factor Xa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347149" }, { "confidence": "medium", "disease": "Intracardiac thrombus", "glycan_involvement": "Glycosylation is essential for factor Xa stability and function.", "mechanism": "Apixaban inhibits factor Xa, reducing risk of intracardiac thrombus.", "protein": "Coagulation factor Xa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347149" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation affects factor Xa's interaction with other coagulation factors.", "mechanism": "Inhibition of factor Xa lowers stroke risk in AF patients.", "protein": "Coagulation factor Xa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347149" }, { "confidence": "medium", "disease": "Major bleeding", "glycan_involvement": "Altered glycosylation may affect factor Xa clearance and bleeding risk.", "mechanism": "Excessive inhibition of factor Xa (especially in low body weight) increases bleeding risk.", "protein": "Coagulation factor Xa", "relationship_type": "causal (adverse effect of therapy)", "source_pmcid": "PMC12347149" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Increased O-acetylated Neu5Ac on N-glycans", "mechanism": "Altered N-glycosylation patterns reflect disease state", "protein": "Serine protease inhibitor A3K", "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Sialylation and O-acetylation status affect function", "mechanism": "Glycosylation changes modulate immune response", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "high", "disease": "Autoimmunity", "glycan_involvement": "Neu5Gc-only sialylation in rat IgG", "mechanism": "Neu5Gc on IgG is immunogenic in humans, may trigger xeno-autoantibodies", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347175" }, { "confidence": "medium", "disease": "Ageing", "glycan_involvement": "Elevated Neu5,9Ac2 on N-glycans with age", "mechanism": "Age-dependent increase in O-acetylated sialylated N-glycans", "protein": "T-kininogen 1", "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "medium", "disease": "Sex hormone-related disorders", "glycan_involvement": "Higher sialylation and O-acetylation in females", "mechanism": "Sex-dependent glycosylation changes reflect hormonal regulation", "protein": "Alpha-1-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "Sialylation/O-acetylation status modulates activity", "mechanism": "Altered glycosylation linked to disease progression", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "medium", "disease": "Drug response", "glycan_involvement": "Neu5Gc-rich N-glycans alter pharmacokinetics", "mechanism": "Glycan structure affects IgG half-life and clearance", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347175" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Altered sialylation/O-acetylation patterns", "mechanism": "Glycosylation changes reflect metabolic state", "protein": "Fetuin-B", "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "low", "disease": "Neurological disorders", "glycan_involvement": "Sialylation/O-acetylation status", "mechanism": "Serum glycoprotein glycosylation linked to disease", "protein": "Protein AMBP", "protein_enriched": { "function": "Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extr", "gene_name": "AMBP", "glycan_count": 104, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G04854VP", "G06247RL", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G18647XP", "G20528HD", "G23505EP", "G27058EU", "G31986NC", "G33416PL", "G37412TK", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G47644PP", "G48414YA", "G50045TK", "G57317CE", "G58087IP", "G59324HL", "G59626AS", "G61256FT", "G63980BQ", "G64527OM", "G68490OW", "G70232NH", "G70619PT", "G72747WU", "G77669RF", "G85282JO", "G86182NS", "G87389XI", "G92551JA", "G94470IW", "G95865ZB", "G98611JV", "G17015OC", "G25426PD", "G43417UB", "G58001LT", "G02030ZB", "G02628JF", "G02815KT", "G04672QB", "G05049YU", "G06010PM", "G06356OH", "G07246CJ", "G08290VR", "G10819WX", "G12579WK", "G14972EH", "G15569GG", "G20425TQ", "G22625SJ", "G24954UD", "G26330YA", "G27516OE", "G27915IV", "G28541PG", "G28681TP", "G30970QQ", "G32259BI", "G34423JR", "G35029YA", "G37995HC", "G40926MX", "G44173IH", "G44215PV", "G46902YN", "G49018RC", "G49906RN", "G54010QB", "G57776ZU", "G58954YZ", "G59536GA", "G60177UT", "G64275UO", "G64409MC", "G66163OV", "G70375MX", "G75256KV", "G75983OB", "G76613WN", "G77547TA", "G78787DI", "G82830MN", "G84862VB", "G85269DF", "G86226EA", "G12728EY", "G22355FZ", "G31936TA", "G49108TO" ], "uniprot_id": "P02760" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "high", "disease": "Biomarker discovery", "glycan_involvement": "Neu5Gc-only sialylation in IgG vs. O-acetylated Neu5Ac in liver proteins", "mechanism": "Distinct glycosylation profiles distinguish cell/tissue origin", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347175" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Aquaporin-4 is a glycoprotein; glycosylation may affect antibody binding and immune recognition.", "mechanism": "AQP4-IgG antibodies target aquaporin-4 on astrocytes, causing complement-mediated astrocyte injury and demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12347217" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may influence antigenicity and antibody detection.", "mechanism": "Presence of AQP4-IgG in CSF is diagnostic for NMOSD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347217" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "Potential role of glycosylation in immune recognition, not directly addressed.", "mechanism": "Dengue infection may trigger AQP4 autoimmunity via molecular mimicry or bystander activation.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal (triggered autoimmunity)", "source_pmcid": "PMC12347217" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Anti-MOG antibodies are diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347217" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Anti-MOG antibodies may be present in ADEM, aiding differential diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347217" }, { "confidence": "high", "disease": "Brainstem syndrome (NMOSD variant)", "glycan_involvement": "Glycosylation may affect AQP4 localization and immune targeting.", "mechanism": "AQP4-IgG mediated astrocyte injury leads to brainstem demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12347217" }, { "confidence": "medium", "disease": "Aspiration pneumonia (secondary to NMOSD)", "glycan_involvement": "Indirect; glycosylation not directly implicated.", "mechanism": "Brainstem NMOSD impairs bulbar function, increasing aspiration risk.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal (secondary effect)", "source_pmcid": "PMC12347217" }, { "confidence": "medium", "disease": "Respiratory failure (secondary to NMOSD)", "glycan_involvement": "Indirect; glycosylation not directly implicated.", "mechanism": "Demyelination of brainstem respiratory centers due to AQP4-IgG.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal (secondary effect)", "source_pmcid": "PMC12347217" }, { "confidence": "low", "disease": "Sepsis (secondary to NMOSD complications)", "glycan_involvement": "Indirect; glycosylation not directly implicated.", "mechanism": "NMOSD-induced aspiration pneumonia leads to sepsis.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal (secondary effect)", "source_pmcid": "PMC12347217" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 syndrome (GBS)", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "GBS and NMOSD may be triggered post-dengue; AQP4-IgG distinguishes NMOSD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC12347217" }, { "confidence": "high", "disease": "Hypoxic Hepatitis", "glycan_involvement": "Bilirubin transport and clearance are mediated by glycoproteins (e.g., albumin, OATP transporters).", "mechanism": "Elevated bilirubin reflects hepatic dysfunction and predicts increased mortality.", "protein": "Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "high", "disease": "Hypoxic Hepatitis", "glycan_involvement": "Prothrombin is N-glycosylated, affecting stability and secretion.", "mechanism": "Prolonged PT-INR indicates impaired hepatic synthesis of glycoprotein coagulation factors, associated with poor prognosis.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "medium", "disease": "Hypoxic Hepatitis", "glycan_involvement": "LDH glycosylation may modulate enzyme stability and clearance.", "mechanism": "Elevated LDH reflects hepatocellular necrosis and is associated with increased mortality.", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "high", "disease": "Hypoxic Hepatitis", "glycan_involvement": "Albumin glycosylation affects half-life and transport capacity.", "mechanism": "Low albumin indicates impaired hepatic synthetic function and is independently associated with mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "medium", "disease": "Coagulation Failure", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation and are essential for hemostasis.", "mechanism": "Low platelet count reflects coagulation failure, a component of MOF and poor prognosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "high", "disease": "Hypoxic Hepatitis", "glycan_involvement": "AST glycosylation may affect enzyme activity and stability.", "mechanism": "Elevated AST is a marker of hepatocellular injury and predicts mortality.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "medium", "disease": "Hypoxic Hepatitis", "glycan_involvement": "ALT glycosylation may influence enzyme secretion.", "mechanism": "Elevated ALT is a marker of liver injury and is used in diagnosis.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "medium", "disease": "Multiple Organ Failure (MOF)", "glycan_involvement": "Altered glycosylation may affect albumin\u2019s anti-inflammatory properties.", "mechanism": "Low albumin is associated with increased risk and severity of MOF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "high", "disease": "Coagulation Failure", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion and function.", "mechanism": "Impaired prothrombin synthesis leads to coagulation failure in MOF.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation of platelet glycoproteins modulates immune and coagulation responses.", "mechanism": "Platelet dysfunction and low count are common in sepsis-induced MOF.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347218" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation of E-cadherin is essential for its adhesive function; disruption may alter glycan-mediated cell-cell adhesion.", "mechanism": "Acetaldehyde-induced hyperphosphorylation disrupts E-cadherin/\u03b2-catenin interaction, leading to adherens junction disassembly and increased permeability.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation modulates \u03b2-catenin stability and interactions.", "mechanism": "Acetaldehyde causes hyperphosphorylation, disrupting \u03b2-catenin/E-cadherin complexes, impairing barrier integrity.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation affects ZO-1 localization and function in tight junctions.", "mechanism": "Acetaldehyde hyperphosphorylates ZO-1, disrupting tight junctions and increasing permeability.", "protein": "ZO-1 (TJP1)", "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Fibronectin glycosylation regulates ECM assembly and cell signaling.", "mechanism": "Acetaldehyde upregulates fibronectin expression in hepatic stellate cells, promoting ECM deposition and fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Collagen glycosylation affects fibril formation and ECM stability.", "mechanism": "Acetaldehyde stimulates COL1A2 transcription via TGF-\u03b2/SMAD3, increasing collagen deposition and fibrosis.", "protein": "Type I Collagen (COL1A2)", "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation modulates MMP-2 secretion and activity.", "mechanism": "Acetaldehyde upregulates MMP-2, promoting ECM remodeling and fibrotic accumulation.", "protein": "Matrix Metalloproteinase-2 (MMP-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation influences MMP-1 stability and function.", "mechanism": "Acetaldehyde downregulates MMP-1, reducing ECM degradation and favoring fibrosis.", "protein": "Matrix Metalloproteinase-1 (MMP-1)", "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Reg3\u03b3 glycosylation is important for antimicrobial activity and barrier function.", "mechanism": "Probiotic-induced upregulation of Reg3\u03b3 enhances intestinal barrier integrity, reducing ethanol-induced liver injury.", "protein": "Regenerating islet-derived protein 3 gamma (Reg3\u03b3)", "protein_enriched": { "function": "Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Restricts bacteria", "gene_name": "REG3G", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6UW15" }, "relationship_type": "protective", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "TGF-\u03b2 glycosylation affects secretion and receptor binding.", "mechanism": "Acetaldehyde activates TGF-\u03b2/SMAD3 pathway, driving fibrogenic gene expression and ECM deposition.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12347242" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation may regulate Nrf2 stability and nuclear translocation.", "mechanism": "Probiotic therapy upregulates Nrf2, enhancing antioxidant response and protecting against ethanol-induced liver injury.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12347242" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "Binds \u03b2-galactoside glycans on host and bacterial surfaces.", "mechanism": "Suppresses Th1/Th17 responses, promotes immune tolerance, facilitating bacterial persistence especially in children.", "protein": "Galectin-1", "relationship_type": "causal", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Chronic gastritis", "glycan_involvement": "Binds glycosylated receptors, induces T cell apoptosis.", "mechanism": "Upregulated in gastric mucosa during chronic gastritis, modulates local immune response.", "protein": "Galectin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "Recognizes \u03b2-galactoside glycans (H type I antigen) on H. pylori LPS.", "mechanism": "Directly binds H. pylori LPS, induces bacterial aggregation and death, strengthens mucosal barrier.", "protein": "Galectin-2", "relationship_type": "protective", "source_pmcid": "PMC12347259" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Crosslinks mucins and adherens junction glycoproteins.", "mechanism": "Stabilizes epithelial junctions, may prevent carcinogenic transformation by maintaining barrier integrity.", "protein": "Galectin-2", "relationship_type": "protective", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "Binds \u03b2-galactoside glycans on H. pylori LPS and host mucins.", "mechanism": "Modulates early immune response, promotes macrophage activation, influences bacterial adhesion and persistence.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Forms multivalent lattices with glycosylated receptors, modulates cell signaling.", "mechanism": "Promotes epithelial survival and proliferative signaling, facilitates carcinogenesis via CagA-dependent pathways.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12347259" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Binds \u03b2-galactoside glycans on immune cells and bacteria.", "mechanism": "Promotes Th17 differentiation and IgA production, enhances mucosal immunity but may also suppress excessive inflammation.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-glycosylation critical for antimicrobial activity.", "mechanism": "O-glycans with terminal \u03b11,4-linked N-acetylglucosamine exhibit direct antimicrobial effects against H. pylori.", "protein": "Mucin 5AC (MUC5AC)", "protein_enriched": { "function": "Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a p", "gene_name": "STAB2", "glycan_count": 6, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G49108TO", "G01650EU", "G27058EU", "G28541PG", "G45504EY", "G63041LO" ], "uniprot_id": "Q8WWQ8" }, "relationship_type": "protective", "source_pmcid": "PMC12347259" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "C-type lectin domain recognizes carbohydrate structures on bacteria.", "mechanism": "Binds H. pylori LPS, inhibits motility, induces aggregation, limits colonization.", "protein": "Surfactant Protein D (SP-D)", "protein_enriched": { "function": "Contributes to the lung's defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modu", "gene_name": "SFTPD", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P35247" }, "relationship_type": "protective", "source_pmcid": "PMC12347259" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Binds exposed \u03b2-galactoside glycans on damaged membranes.", "mechanism": "Promotes antibacterial autophagy by recognizing damaged vacuolar membranes.", "protein": "Galectin-8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347259" }, { "confidence": "high", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "AMH is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "AMH inhibits primordial follicle activation and induces autophagy via FOXO3A, reducing chemotherapy-induced PMF loss.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation required for AMH bioactivity and serum detection.", "mechanism": "AMH levels reflect ovarian reserve and predict fertility status post-chemotherapy.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Chemotherapy-induced Gonadotoxicity", "glycan_involvement": "G-CSF is a glycoprotein; glycosylation affects receptor binding and half-life.", "mechanism": "G-CSF promotes neovascularization, reducing follicle loss and extending time to POI after chemotherapy.", "protein": "Granulocyte Colony-Stimulating Factor (G-CSF)", "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Chemotherapy-induced Gonadotoxicity", "glycan_involvement": "LH is a glycoprotein; glycosylation is critical for receptor interaction.", "mechanism": "LH activates anti-apoptotic signals, reduces TAp63, and promotes DNA repair in oocytes.", "protein": "Luteinizing Hormone (LH)", "protein_enriched": { "function": "Promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids", "gene_name": "LHB", "glycan_count": 32, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G06209KS", "G06356OH", "G10258MC", "G14047PA", "G14998UC", "G22310AV", "G24413UY", "G24835MQ", "G25835MT", "G26403SG", "G28975ZZ", "G32659RY", "G39540XG", "G40671AG", "G43346PX", "G46422KL", "G48414YA", "G49743VF", "G53933HU", "G53985AY", "G54612UD", "G56271TF", "G56345UO", "G57196QI", "G72291OX", "G78890OB", "G81198YO", "G83951ZY", "G84467IZ", "G91365ZQ", "G96921ZU", "G99897FQ" ], "uniprot_id": "P01229" }, "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "high", "disease": "Ovarian Atrophy", "glycan_involvement": "Glycosylation required for AMH function.", "mechanism": "AMH administration preserves PMF pool and prevents follicular depletion during chemotherapy.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "Glycosylation modulates G-CSF activity.", "mechanism": "G-CSF increases follicle counts and AMH levels post-chemotherapy, delaying POI onset.", "protein": "Granulocyte Colony-Stimulating Factor (G-CSF)", "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Chemotherapy-induced Gonadotoxicity", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects receptor binding.", "mechanism": "VEGF co-administration with G-CSF reduces follicle loss, but may promote tumor angiogenesis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Radiation-induced Gonadotoxicity", "glycan_involvement": "Glycosylation required for AMH stability and function.", "mechanism": "AMH limits PMF activation and loss after radiation exposure.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Radiation-induced Gonadotoxicity", "glycan_involvement": "Glycosylation required for G-CSF bioactivity.", "mechanism": "G-CSF improves ovarian vascularization and reduces follicle loss after radiation.", "protein": "Granulocyte Colony-Stimulating Factor (G-CSF)", "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "medium", "disease": "Premature Ovarian Insufficiency (POI)", "glycan_involvement": "LH glycosylation essential for function.", "mechanism": "LH reduces pro-apoptotic factors and modulates follicle activation, preserving ovarian reserve.", "protein": "Luteinizing Hormone (LH)", "protein_enriched": { "function": "Promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids", "gene_name": "LHB", "glycan_count": 32, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G06209KS", "G06356OH", "G10258MC", "G14047PA", "G14998UC", "G22310AV", "G24413UY", "G24835MQ", "G25835MT", "G26403SG", "G28975ZZ", "G32659RY", "G39540XG", "G40671AG", "G43346PX", "G46422KL", "G48414YA", "G49743VF", "G53933HU", "G53985AY", "G54612UD", "G56271TF", "G56345UO", "G57196QI", "G72291OX", "G78890OB", "G81198YO", "G83951ZY", "G84467IZ", "G91365ZQ", "G96921ZU", "G99897FQ" ], "uniprot_id": "P01229" }, "relationship_type": "protective", "source_pmcid": "PMC12347271" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects HDL particle stability and function.", "mechanism": "HDL-C levels increase after bariatric surgery, associated with reduced cardiovascular risk.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "LDL-C levels are higher in females; changes post-surgery may impact cardiovascular risk.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation influences lipoprotein assembly.", "mechanism": "TC levels are monitored to assess lipid metabolism after surgery.", "protein": "TC", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects lipoprotein lipase activity.", "mechanism": "TG levels decrease after surgery, indicating improved lipid metabolism.", "protein": "TG", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "ALT levels reflect liver injury; changes post-surgery indicate hepatic improvement.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "AST levels are used to monitor liver function after surgery.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects enzyme localization and activity.", "mechanism": "GGT levels are elevated in liver dysfunction; reduction post-surgery signals improvement.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates HDL function.", "mechanism": "Lower HDL-C is associated with obesity; increase post-surgery reflects metabolic improvement.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "high", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "Glycosylation affects TG metabolism.", "mechanism": "Elevated TG is linked to insulin resistance and T2D; reduction post-surgery indicates improved glycemic control.", "protein": "TG", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation impacts HDL particle remodeling.", "mechanism": "HDL-C is a key marker for dyslipidemia; direct association with genetic risk score post-surgery.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12347326" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "NPC1L1 is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "Mediates intestinal cholesterol absorption; unchanged in MASLD, but its function is central to cholesterol influx.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Effluxes plant sterols and cholesterol back to intestinal lumen; unchanged in MASLD, but relevant for cholesterol balance.", "protein": "ABCG5", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation impacts stability and function.", "mechanism": "Partners with ABCG5 in cholesterol efflux; unchanged in MASLD, but critical for absorption regulation.", "protein": "ABCG8", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane. Plays an essential role in the selective transport of the dietary choles", "gene_name": "ABCG8", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H221" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "NLRP3 is glycosylated; glycosylation may modulate inflammasome assembly.", "mechanism": "Activated by cholesterol crystals in hepatocytes, triggering inflammation in MASLD.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "NRF2 glycosylation may affect nuclear translocation and activity.", "mechanism": "NRF2-dependent activation of NLRP3 inflammasome by cholesterol crystals promotes inflammation.", "protein": "NRF2", "relationship_type": "causal", "source_pmcid": "PMC12347333" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation essential for ABCA1 function and HDL formation.", "mechanism": "Cholesterol efflux transporter; decreased activity in MASLD impairs cholesterol removal.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for stability and trafficking.", "mechanism": "Cholesterol efflux transporter; reduced capacity in MASLD contributes to cholesterol accumulation.", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation critical for enzymatic activity.", "mechanism": "Catalyzes cholesterol esterification; altered activity may affect HDL metabolism in MASLD.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates CETP secretion and function.", "mechanism": "Transfers cholesterol esters between lipoproteins; may be altered in MASLD.", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation influences enzyme stability.", "mechanism": "Catalyzes cholesterol conversion to bile acids; altered in MASLD, affecting cholesterol elimination.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347333" }, { "confidence": "high", "disease": "Lysosomal Storage Disorder (Fabry Disease)", "glycan_involvement": "GLA is a glycoprotein; glycosylation is essential for lysosomal targeting and activity", "mechanism": "Exosome-mediated delivery of GLA restores enzyme activity in CNS", "protein": "Alpha-galactosidase A (GLA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347363" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "VEGF glycosylation affects secretion and receptor binding", "mechanism": "Stem cell-derived VEGF promotes angiogenesis and cerebral blood flow recovery", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "protective", "source_pmcid": "PMC12347363" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "AQP4 glycosylation modulates membrane localization and water channel function", "mechanism": "Stem cell therapy preserves BBB via PKC\u03b4/AQP4 pathway", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "protective", "source_pmcid": "PMC12347363" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "RVG29 glycosylation is critical for neuronal receptor binding", "mechanism": "RVG29-modified exosomes enhance neuronal targeting and reduce apoptosis", "protein": "Rabies Virus Glycoprotein (RVG29)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347363" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "IFN-gamma glycosylation affects stability and receptor interaction", "mechanism": "MSC-overexpressed IFN-gamma failed to inhibit tumor growth", "protein": "Interferon gamma", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347363" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Polysialylation of NCAM regulates cell migration and plasticity", "mechanism": "Stem cell therapy enhances neurogenesis and migration via NCAM-mediated adhesion", "protein": "Neural Cell Adhesion Molecule (NCAM)", "protein_enriched": { "function": "This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc", "gene_name": "NCAM1", "glycan_count": 26, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G16125XL", "G25418HZ", "G27058EU", "G30769VJ", "G31852PQ", "G41071NU", "G43223CG", "G50045TK", "G59626AS", "G60177UT", "G68490OW", "G70441OD", "G80223IX", "G80479JV", "G82830MN", "G91636VS", "G95865ZB", "G11314AS", "G67031OU", "G43669FQ" ], "uniprot_id": "P13591" }, "relationship_type": "protective", "source_pmcid": "PMC12347363" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "VLA-4 glycosylation modulates integrin activation and cell adhesion", "mechanism": "VLA-4 overexpression increases stem cell adhesion to endothelium, improving engraftment", "protein": "Very Late Antigen-4 (VLA-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347363" }, { "confidence": "low", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation may affect calcineurin stability and secretion", "mechanism": "Calcineurin released from stem cells alleviates apoptosis in damaged neurons", "protein": "Calcineurin", "protein_enriched": { "function": "Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription fa", "gene_name": "PPP3CC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48454" }, "relationship_type": "protective", "source_pmcid": "PMC12347363" }, { "confidence": "low", "disease": "Ischemic Stroke", "glycan_involvement": "PKC\u03b4 glycosylation may regulate kinase activity", "mechanism": "PKC\u03b4 pathway involved in BBB protection after stem cell therapy", "protein": "Protein Kinase C delta (PKC\u03b4)", "protein_enriched": { "function": "Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic pro", "gene_name": "PRKCD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05655" }, "relationship_type": "protective", "source_pmcid": "PMC12347363" }, { "confidence": "low", "disease": "Ischemic Stroke", "glycan_involvement": "Nestin glycosylation may affect filament assembly", "mechanism": "Nestin expression marks neurogenesis after stem cell therapy", "protein": "Nestin", "protein_enriched": { "function": "Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF pro", "gene_name": "NES", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347363" }, { "confidence": "high", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "CRP is heavily N-glycosylated, which affects its stability and immune recognition.", "mechanism": "Elevated CRP reflects systemic chronic inflammation associated with poor prognosis in SCC.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "high", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "SAA glycosylation modulates its solubility and inflammatory activity.", "mechanism": "High SAA levels indicate chronic inflammation and correlate with low LPC and poor prognosis.", "protein": "Serum amyloid A protein", "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "Multiple N-glycosylation sites influence immune interactions.", "mechanism": "Upregulated in low-LPC SCC patients, marking systemic inflammation.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-6 glycosylation affects receptor binding and stability.", "mechanism": "IL-6 is elevated in low-LPC SCC patients, driving chronic inflammation and poor immunotherapy response.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12347404" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and bioactivity.", "mechanism": "TNF-\u03b1 is increased in low-LPC SCC, promoting systemic inflammation and immune exhaustion.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Poor immunotherapy response", "glycan_involvement": "IL-10 glycosylation regulates anti-inflammatory function.", "mechanism": "Elevated IL-10 in low-LPC SCC patients may suppress antitumor immunity, reducing ICI efficacy.", "protein": "Interleukin-10", "relationship_type": "causal", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "Higher CCL2 in high-LPC SCC patients, associated with distinct inflammatory profiles.", "protein": "CCL2 (Monocyte chemoattractant protein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "Glycosylation modulates receptor binding and chemotactic activity.", "mechanism": "CXCL8 is elevated in high-LPC SCC, marking a different inflammatory state.", "protein": "CXCL8 (Interleukin-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Poor immunotherapy response", "glycan_involvement": "PD-L1 N-glycosylation regulates immune checkpoint function and stability.", "mechanism": "PD-L1 expression is independent of LPC levels, but both are predictors of ICI response.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "medium", "disease": "Coagulation abnormalities", "glycan_involvement": "N-glycosylation impacts interaction with coagulation factors.", "mechanism": "Upregulated in low-LPC SCC, associated with activation of coagulation pathways.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347404" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "MBL recognizes altered glycan structures (neoepitopes) on renal cells due to hyperglycemia.", "mechanism": "MBL binds to hyperglycemia-exposed renal cells, activates complement, drives inflammation and renal damage.", "protein": "Mannan-binding lectin (MBL)", "relationship_type": "causal", "source_pmcid": "PMC12347418" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Fibronectin is a glycoprotein; altered glycosylation may affect ECM accumulation.", "mechanism": "Increased fibronectin deposition in glomeruli correlates with renal damage in diabetic mice.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347418" }, { "confidence": "low", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "SERPINB2 is glycosylated, but glycan changes not implicated in DKD.", "mechanism": "Genetic variants of SERPINB2 were tested for association with DKD; no significant link found.", "protein": "SERPINB2", "protein_enriched": { "function": "Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1", "gene_name": "SERPINB2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05120" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347418" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "S1R is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "S1R activation by fluvoxamine protects against inflammation, hypoxia, and fibrosis in DKD models.", "protein": "Sigma-1 receptor (S1R)", "protein_enriched": { "function": "Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma memb", "gene_name": "SIGMAR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99720" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347418" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "KIM-1 is glycosylated; glycan status may influence detection and function.", "mechanism": "Elevated urinary and renal KIM-1 levels indicate tubular injury in DKD; reduced by S1R agonist.", "protein": "KIM-1 (Havcr1)", "protein_enriched": { "function": "Phosphatidylserine receptor that plays an important functional role in regulatory B-cells homeostasis including generation, expansion and suppressor functions (By similarity). As P-selectin/SELPLG lig", "gene_name": "HAVCR1", "glycan_count": 5, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G43417UB", "G02815KT", "G15664MX", "G23719VF", "G94470IW" ], "uniprot_id": "Q96D42" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347418" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "NGAL is glycosylated; glycan modifications may affect secretion and stability.", "mechanism": "NGAL levels are increased in DKD and reduced by S1R activation, reflecting tubular injury.", "protein": "NGAL (LCN2)", "relationship_type": "biomarker", "source_pmcid": "PMC12347418" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "C3 is glycosylated; glycan changes may affect complement activation.", "mechanism": "Increased C3 mRNA and circulating levels indicate complement activation and inflammation in DN.", "protein": "C3 complement", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347418" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "C4 is glycosylated; glycan status may influence complement pathway activation.", "mechanism": "Increased C4 deposition in glomeruli reflects complement activation in DN.", "protein": "C4 complement", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347418" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "TGF-\u03b21 is glycosylated; glycan modifications may regulate activity.", "mechanism": "TGF-\u03b21 induces fibroblast transformation and ECM deposition, driving fibrosis in DKD.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12347418" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Collagen I is glycosylated; glycan status affects ECM structure.", "mechanism": "Col1a1 expression and deposition are markers and mediators of fibrosis in DKD.", "protein": "Collagen I (Col1a1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347418" }, { "confidence": "medium", "disease": "Songling virus disease", "glycan_involvement": "GPC is likely glycosylated, as in related nairoviruses, facilitating host cell entry and immune evasion.", "mechanism": "Encodes viral glycoprotein essential for viral entry and pathogenesis in humans.", "protein": "SGLV glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12347420" }, { "confidence": "medium", "disease": "Beiji nairovirus disease", "glycan_involvement": "GPC is predicted to be glycosylated, aiding in host cell attachment and immune modulation.", "mechanism": "Encodes viral glycoprotein required for viral entry and infection in humans.", "protein": "BJNV glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12347420" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "N-glycosylation is known to be critical for CCHFV GPC function and immune evasion.", "mechanism": "Viral glycoprotein mediates host cell entry and is essential for viral infectivity and pathogenesis.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347420" }, { "confidence": "medium", "disease": "Songling virus disease", "glycan_involvement": "Glycosylation sites may be targeted for vaccine design or antiviral strategies.", "mechanism": "GPC structure provides a basis for vaccine and antiviral drug development.", "protein": "SGLV glycoprotein precursor (GPC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347420" }, { "confidence": "medium", "disease": "Beiji nairovirus disease", "glycan_involvement": "Potential glycosylation sites could be exploited for immune targeting.", "mechanism": "GPC is a candidate for antiviral and vaccine development.", "protein": "BJNV glycoprotein precursor (GPC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347420" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "N-glycans modulate antigenicity and immune recognition.", "mechanism": "GPC is a validated target for antiviral drugs and vaccines.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347420" }, { "confidence": "high", "disease": "Cystic fibrosis-associated liver disease (CFLD)", "glycan_involvement": "CFTR is a glycoprotein; glycosylation affects its folding, trafficking, and function.", "mechanism": "CFTR dysfunction alters bile composition and excretion, leading to biliary stasis, ductal injury, and chronic hepatic inflammation.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12347444" }, { "confidence": "high", "disease": "Cystic fibrosis (CF)", "glycan_involvement": "Glycosylation status influences CFTR stability and cell surface expression.", "mechanism": "Mutations in CFTR gene cause defective chloride channel function, resulting in multisystem disease.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Cystic fibrosis-associated liver disease (CFLD)", "glycan_involvement": "AST is glycosylated, which may affect its serum stability.", "mechanism": "Elevated AST is used in FIB-4 index to estimate liver fibrosis in CFLD.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Cystic fibrosis-associated liver disease (CFLD)", "glycan_involvement": "ALT glycosylation may influence its release and detection.", "mechanism": "ALT levels are part of FIB-4 index for non-invasive fibrosis assessment.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function; altered in liver disease.", "mechanism": "Platelet count (reflecting glycoprotein function) is reduced in advanced fibrosis and used in FIB-4 index.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Cystic fibrosis-associated liver disease (CFLD)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "Elevated GGT is a biochemical marker for CFLD diagnosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation defects may exacerbate CFTR misfolding and loss of function.", "mechanism": "CFTR dysfunction leads to chronic hepatic inflammation and fibrosis.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Aberrant glycosylation may worsen CFTR trafficking defects.", "mechanism": "Progressive CFLD due to CFTR dysfunction can result in cirrhosis.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation status may modulate CFTR function and disease severity.", "mechanism": "Advanced CFLD from CFTR dysfunction leads to portal hypertension.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12347444" }, { "confidence": "medium", "disease": "Cystic fibrosis-associated liver disease (CFLD)", "glycan_involvement": "Modulators may affect glycosylation and trafficking of CFTR.", "mechanism": "CFTR modulators (e.g., ivacaftor) aim to restore CFTR function, potentially impacting liver disease progression.", "protein": "CFTR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347444" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "N-glycosylation modulates adhesive function and stability.", "mechanism": "Downregulation during EMT reduces cell-cell adhesion, promoting lesion invasiveness.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "N-glycosylation affects cell migration and adhesion.", "mechanism": "Upregulation during EMT enhances migratory and invasive properties of ectopic cells.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Heavily glycosylated; glycosylation influences cell adhesion and signaling.", "mechanism": "Overexpression coincides with cadherin switch, promoting EMT and disease progression.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation regulates tight junction assembly and barrier function.", "mechanism": "Downregulation impairs tight junctions, facilitating EMT and invasiveness.", "protein": "Claudin-3", "protein_enriched": { "function": "Barrier-forming claudin. Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity", "gene_name": "CLDN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15551" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation modulates tight junction integrity.", "mechanism": "Reduced expression in ectopic lesions supports EMT and loss of epithelial traits.", "protein": "Claudin-4", "protein_enriched": { "function": "Can associate with other claudins to regulate tight junction structural and functional strand dynamics (PubMed:35773259, PubMed:36008380). May coassemble with CLDN8 into tight junction strands contain", "gene_name": "CLDN4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14493" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation affects membrane localization.", "mechanism": "Altered localization in ectopic tissue indicates partial EMT.", "protein": "Claudin-7", "protein_enriched": { "function": "Plays a major role in tight junction-specific obliteration of the intercellular space", "gene_name": "CLDN7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95471" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation influences tight junction formation.", "mechanism": "Impaired localization in ectopic tissue suggests EMT involvement.", "protein": "Claudin-11", "relationship_type": "biomarker", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Ovarian endometrioma (OMA)", "glycan_involvement": "Sialylated glycan ligands mediate cell adhesion and migration.", "mechanism": "Reduced expression in OMA indicates mesenchymal phenotype and active EMT.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347505" }, { "confidence": "medium", "disease": "Deep infiltrating endometriosis (DIE)", "glycan_involvement": "Glycosylation mediates cell-cell interactions.", "mechanism": "Strong expression in DIE suggests retention of epithelial features.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347505" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Upregulation marks EMT and correlates with increased cell motility and invasiveness.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347505" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects SAA stability and secretion, influencing its circulating levels.", "mechanism": "SAA activity reflects AMY1 gene copy number and is associated with susceptibility to obesity via altered starch metabolism and energy homeostasis.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect SAA enzymatic activity and interaction with substrates.", "mechanism": "Altered SAA levels modulate postprandial insulin dynamics, impacting insulin sensitivity.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Glucose intolerance", "glycan_involvement": "Glycosylation may modulate SAA's substrate specificity and function.", "mechanism": "SAA-driven differences in starch digestion influence glycemic excursions and glucose tolerance.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation status may affect SAA secretion in metabolic syndrome.", "mechanism": "Altered SAA profiles observed in metabolic syndrome, reflecting neuroendocrine and metabolic dysregulation.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation may influence SAA's stability in diabetic conditions.", "mechanism": "Individuals with diabetes often display altered SAA activity, potentially linked to impaired glucose homeostasis.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Visceral adiposity", "glycan_involvement": "Glycosylation may impact SAA secretion and function in adiposity.", "mechanism": "Low SAA levels are associated with increased visceral fat, independent of BMI.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "low", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation may affect SAA's interaction with oral tissues.", "mechanism": "Oral inflammation alters SAA secretion; SAA may reflect oral mucosal health.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "low", "disease": "Xerostomia", "glycan_involvement": "Glycosylation may influence SAA stability in low-fluid environments.", "mechanism": "Reduced salivary flow in xerostomia affects SAA concentration and activity.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "high", "disease": "Psychological stress-related disorders", "glycan_involvement": "Glycosylation may modulate SAA secretion in response to stress.", "mechanism": "SAA is a surrogate marker of sympathetic nervous system activation during acute and chronic stress.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may affect SAA's circulatory half-life and detection.", "mechanism": "SAA serves as a non-invasive indicator of autonomic dysfunction, which is linked to cardiovascular risk.", "protein": "Salivary \u03b1-amylase (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12347534" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated serum AST reflects hepatocyte injury and correlates with fibrosis stage.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation modulates ALT secretion and activity.", "mechanism": "ALT elevation is indicative of hepatocellular damage in fibrosis.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation influences GGT enzymatic activity.", "mechanism": "Serum GGT increases with cholestasis and fibrosis progression.", "protein": "GGT (Gamma-Glutamyl Transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "N-glycosylation regulates ALP stability and function.", "mechanism": "ALP elevation is associated with biliary involvement in fibrosis.", "protein": "ALP (Alkaline Phosphatase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation affects platelet lifespan and function.", "mechanism": "Platelet count (APRI index) is inversely correlated with fibrosis severity.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation impacts albumin stability and transport.", "mechanism": "Hypoalbuminemia reflects advanced liver dysfunction in cirrhosis.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Steatohepatitis (MASH)", "glycan_involvement": "Glycosylation modulates AST serum levels.", "mechanism": "AST elevation is a marker of hepatocyte ballooning and inflammation.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Steatohepatitis (MASH)", "glycan_involvement": "Glycosylation affects ALT secretion.", "mechanism": "ALT is elevated in active steatohepatitis.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation influences GGT activity.", "mechanism": "GGT is increased in MASLD due to oxidative stress and lipid accumulation.", "protein": "GGT (Gamma-Glutamyl Transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation regulates platelet clearance.", "mechanism": "Thrombocytopenia due to splenic sequestration and decreased thrombopoietin in cirrhosis.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12347550" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects membrane localization and substrate specificity.", "mechanism": "Mediates drug efflux, affecting chemotherapy efficacy and drug\u2013drug interactions with anticoagulants.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347568" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation may regulate inflammasome assembly and activation.", "mechanism": "NLRP3 inflammasome activation drives atrial inflammation and fibrosis, promoting AF.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12347568" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation may modulate NLRP3 function and immune signaling.", "mechanism": "NLRP3-mediated inflammation promotes cancer initiation, immunosuppression, and metastasis.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12347568" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Pro-inflammatory cytokine induces atrial remodeling and fibrosis, increasing AF risk.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12347568" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation essential for stability and activity.", "mechanism": "Promotes pro-inflammatory and pro-fibrotic state in atrial myocardium.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12347568" }, { "confidence": "medium", "disease": "Chemotherapy-induced Cardiotoxicity", "glycan_involvement": "N-glycosylation modulates receptor dimerization and signaling.", "mechanism": "HER-2 antagonists can induce AF and cardiotoxicity in cancer patients.", "protein": "HER-2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347568" }, { "confidence": "medium", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation affects enzyme activity and substrate recognition.", "mechanism": "MMPs contribute to extracellular matrix remodeling and fibrosis, promoting AF.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347568" }, { "confidence": "low", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Elevated in epicardial fat, promotes pro-fibrotic state in atria.", "protein": "Activin A", "protein_enriched": { "function": "Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythr", "gene_name": "INHBA", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G70994MS" ], "uniprot_id": "P08476" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347568" }, { "confidence": "low", "disease": "Chemotherapy-induced Cardiotoxicity", "glycan_involvement": "N-glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "CXCR4 levels increase with cardiac injury; dapagliflozin reduces CXCR4 in preclinical models.", "protein": "C-X-C chemokine receptor type 4 (CXCR4)", "relationship_type": "biomarker", "source_pmcid": "PMC12347568" }, { "confidence": "medium", "disease": "Thromboembolism", "glycan_involvement": "Glycosylation influences transporter function and drug interactions.", "mechanism": "P-gp modulates NOAC and chemotherapeutic drug levels, impacting thromboembolic risk in cancer patients with AF.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347568" }, { "confidence": "high", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Exposure of S-antigen due to blood-retina barrier disruption triggers autoimmune response.", "protein": "Arrestin (S-antigen)", "protein_enriched": { "function": "Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO (By similarity). May play a role in preventing lig", "gene_name": "SAG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10523" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "high", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation may modulate immunogenicity.", "mechanism": "Autoimmune response against recoverin following ocular tissue damage.", "protein": "Recoverin", "protein_enriched": { "function": "Acts as a calcium sensor and regulates phototransduction of cone and rod photoreceptor cells (By similarity). Modulates light sensitivity of cone photoreceptor in dark and dim conditions (By similarit", "gene_name": "RCVRN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35243" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "high", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation influences antigen presentation.", "mechanism": "Autoantigen exposure leads to immune-mediated uveitis.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "medium", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Melanocyte-associated antigen exposure induces autoimmune attack.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "medium", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation status may influence immunogenicity.", "mechanism": "Exposure of IRBP triggers T-cell mediated autoimmunity.", "protein": "Interphotoreceptor retinoid-binding protein (IRBP)", "protein_enriched": { "function": "Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-tra", "gene_name": "RLBP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12271" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "medium", "disease": "Sympathetic Ophthalmia", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Autoimmune response following antigen exposure due to tissue damage.", "protein": "Retinal pigment epithelium-associated antigens", "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "medium", "disease": "Choroidal Melanoma", "glycan_involvement": "Glycosylation may affect protein stability and detection.", "mechanism": "Tyrosinase is expressed in melanocytic tumors and used for diagnosis.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347612" }, { "confidence": "low", "disease": "Vogt\u2013Koyanagi\u2013Harada (VKH) Syndrome", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Autoimmune response against ocular antigens including S-antigen.", "protein": "Arrestin (S-antigen)", "protein_enriched": { "function": "Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO (By similarity). May play a role in preventing lig", "gene_name": "SAG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10523" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "low", "disease": "TINU Syndrome", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoimmune response against recoverin in uveitis.", "protein": "Recoverin", "protein_enriched": { "function": "Acts as a calcium sensor and regulates phototransduction of cone and rod photoreceptor cells (By similarity). Modulates light sensitivity of cone photoreceptor in dark and dim conditions (By similarit", "gene_name": "RCVRN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35243" }, "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "low", "disease": "Choroidal Melanoma", "glycan_involvement": "Glycosylation may affect antigen exposure.", "mechanism": "Tumor necrosis exposes antigens, potentially triggering immune response.", "protein": "Retinal pigment epithelium-associated antigens", "relationship_type": "causal", "source_pmcid": "PMC12347612" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates P-glycoprotein stability and drug efflux function.", "mechanism": "Targeted by repurposed drugs (fluphenazine, sertraline) to overcome drug resistance and affect tumor growth pathways (Akt, Wnt).", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects ABCB1 trafficking and function.", "mechanism": "Targeted by repurposed drugs (fluphenazine, sertraline) to modulate multidrug resistance in cancer cells.", "protein": "ABCB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation status influences P-glycoprotein activity.", "mechanism": "Fluphenazine shown to alter P-glycoprotein in lung cancer cells, impacting drug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates efflux capacity and drug sensitivity.", "mechanism": "Fluphenazine and sertraline affect P-glycoprotein, reducing drug resistance in breast cancer cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "low", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects substrate specificity and resistance.", "mechanism": "Efavirenz repurposing in colorectal cancer may involve modulation of P-glycoprotein-mediated drug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "low", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation influences protein localization and function.", "mechanism": "Efavirenz repurposing in pancreatic cancer may target P-glycoprotein to overcome resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347644" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "ALP levels increase with worsening glycemic control, reflecting hepatic insulin resistance and systemic inflammation.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation modulates ALP activity in renal tissue.", "mechanism": "Elevated ALP is associated with nephropathy and bone metabolism changes in diabetes.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin (not classical glycosylation).", "mechanism": "HbA1c reflects average blood glucose and is used for diagnosis and monitoring.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "LDL contains glycoprotein apolipoproteins; glycosylation affects receptor binding and clearance.", "mechanism": "LDL levels are altered in T2DM, affecting atherogenic risk.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "HDL apolipoproteins are glycosylated, influencing anti-atherogenic properties.", "mechanism": "Reduced HDL in uncontrolled diabetes increases CVD risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Albumin glycation increases in diabetes, affecting renal filtration.", "mechanism": "Albumin levels and glycation status reflect renal function and damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "GGT is glycosylated; glycan structure affects enzyme activity.", "mechanism": "Elevated GGT is linked to hepatic fat accumulation in T2DM.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Albumin glycosylation may affect bilirubin binding and antioxidant capacity.", "mechanism": "Lower direct bilirubin in uncontrolled diabetes suggests reduced antioxidant defense.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "protective", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation modulates ALP activity in vascular tissue.", "mechanism": "ALP elevation is associated with vascular calcification in T2DM.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "medium", "disease": "Bone metabolism disorder", "glycan_involvement": "Glycosylation affects ALP isoform distribution and bone activity.", "mechanism": "ALP reflects bone turnover, which is altered in diabetes.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347671" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "Glycosylation may affect stability and immune modulation.", "mechanism": "Elevated in DED tears; reduced after anti-inflammatory therapy.", "protein": "Apolipoprotein A-I", "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "N-glycosylation modulates anti-protease activity.", "mechanism": "Increased in DED; reduction correlates with decreased inflammation.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "medium", "disease": "Dry Eye Disease", "glycan_involvement": "Glycosylation may regulate anti-inflammatory function.", "mechanism": "Upregulated in DED; reduced after therapy, indicating inflammation resolution.", "protein": "Annexin A1", "protein_enriched": { "function": "Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a", "gene_name": "ANXA1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P04083" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "Potential O-glycosylation affects immune signaling.", "mechanism": "Elevated in DED; reduction after therapy marks decreased inflammation.", "protein": "Protein S100-A8", "protein_enriched": { "function": "S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominan", "gene_name": "S100A8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05109" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "Glycosylation may modulate inflammatory activity.", "mechanism": "Increased in DED; normalized after anti-inflammatory treatment.", "protein": "Protein S100-A9", "protein_enriched": { "function": "S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response (PubMed:12626582, PubMed:15331440, PubMed:16258195, PubMed:19", "gene_name": "S100A9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06702" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Dry Eye Disease", "glycan_involvement": "N-glycosylation essential for inhibitory function.", "mechanism": "Reduced in DED; increased after therapy, inhibits MMP9 and protects tissue.", "protein": "Metalloproteinase inhibitor 1 (TIMP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347701" }, { "confidence": "medium", "disease": "Aqueous-deficient Dry Eye", "glycan_involvement": "N-glycosylation critical for complement activity.", "mechanism": "Upregulated in severe DED; reduced after therapy, indicating complement activation.", "protein": "Complement C4-B/C4A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "medium", "disease": "Aqueous-deficient Dry Eye", "glycan_involvement": "N-glycosylation affects transport and immune modulation.", "mechanism": "Elevated in severe DED; reduction after therapy reflects decreased inflammation.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Aqueous-deficient Dry Eye", "glycan_involvement": "Extensive O-glycosylation critical for mucin function.", "mechanism": "Upregulated in severe DED; reduced after therapy, involved in mucosal protection.", "protein": "Mucin-5AC", "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "medium", "disease": "Aqueous-deficient Dry Eye", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune response.", "mechanism": "Elevated in severe DED; reduction after therapy indicates decreased tissue remodeling.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347701" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Heavily glycosylated, required for secretion and receptor binding.", "mechanism": "Promotes tumor growth, metastasis, and immunosuppressive TME via STAT3 activation and M2 macrophage polarization.", "protein": "IL-19", "protein_enriched": { "function": "Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine (PubMed:10585463, PubMed:11078725, PubMed:12186880). Only active again", "gene_name": "PCYOX1", "glycan_count": 66, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00406II", "G00912UN", "G02815KT", "G04657PL", "G05724UK", "G06110VR", "G08918WF", "G10819WX", "G11009FR", "G14260UH", "G23719VF", "G25637MV", "G27058EU", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G46503DX", "G46691LC", "G47448YK", "G49874UX", "G59626AS", "G62765YT", "G64527OM", "G67164EE", "G70101JE", "G72291OX", "G72747WU", "G80333GO", "G80920RR", "G83460ZZ", "G83633GK", "G87399DK", "G92050GC", "G92275SC", "G95865ZB", "G11629QQ", "G57888GL", "G04854VP", "G05049YU", "G25079LO", "G27126ED", "G49018RC", "G57776ZU", "G58087IP", "G72790NZ", "G77547TA", "G90659AW", "G13694XX", "G18647XP", "G22310AV", "G28541PG", "G31936TA", "G35029YA", "G39446WN", "G42124LM", "G45504EY", "G49955PK", "G56784JY", "G57317CE", "G59924QI", "G62461SM", "G62894KT", "G70619PT", "G73968GN", "G49108TO" ], "uniprot_id": "Q9UHG3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Glycosylation required for stability and receptor interaction.", "mechanism": "Elevated IL-20 correlates with poor prognosis; blockade inhibits tumor growth and PD-L1 expression.", "protein": "IL-20", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Promotes tumor growth, stemness, and angiogenesis via STAT3 and ERK signaling; high IL-22RA1 expression linked to poor prognosis.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Suppresses tumor growth and colony formation; loss of IL-24 correlates with progression.", "protein": "IL-24", "protein_enriched": { "function": "Multifunctional cytokine mainly produced by T-cells that plays a regulatory role in immune response, tissue homeostasis, host defense, and oncogenesis (PubMed:25168428, PubMed:27687232). Possesses ant", "gene_name": "IL24", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q13007" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12347730" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation required for cytokine function.", "mechanism": "Elevated IL-26 levels correlate with advanced stage and poor prognosis.", "protein": "IL-26", "protein_enriched": { "function": "May play a role in local mechanisms of mucosal immunity and seems to have a pro-inflammatory function. May play a role in inflammatory bowel disease. Activates STAT1 and STAT3, MAPK1/3 (ERK1/2), JUN a", "gene_name": "IL26", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPH9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation required for membrane localization and ligand binding.", "mechanism": "Upregulated in tumor tissue; promotes stemness and tumor growth via JAK1\u2013STAT3\u2013SOX2 pathway.", "protein": "IL-20RA", "protein_enriched": { "function": "Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcript", "gene_name": "AICDA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9GZX7" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12347730" }, { "confidence": "medium", "disease": "Papillary Renal Cell Carcinoma", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Promotes proliferation, migration, and invasion via STAT3 and EMT markers; knockdown reduces tumor aggressiveness.", "protein": "IL-20RB", "protein_enriched": { "function": "The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL22RA1/IL20RB dimer is a receptor for IL20 and IL24", "gene_name": "IL20RB", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU" ], "uniprot_id": "Q6UXL0" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347730" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for cytokine activity.", "mechanism": "Acts on bone marrow stromal cells to promote myeloma cell survival and immune evasion.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Low IL-24 expression correlates with poor outcome; induces apoptosis and inhibits angiogenesis.", "protein": "IL-24", "protein_enriched": { "function": "Multifunctional cytokine mainly produced by T-cells that plays a regulatory role in immune response, tissue homeostasis, host defense, and oncogenesis (PubMed:25168428, PubMed:27687232). Possesses ant", "gene_name": "IL24", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q13007" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Glycosylation required for membrane localization and ligand binding.", "mechanism": "High expression linked to increased stemness and tumorigenicity via STAT3 signaling.", "protein": "IL-22RA1", "protein_enriched": { "function": "Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 an", "gene_name": "IL22RA1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00395TQ" ], "uniprot_id": "Q8N6P7" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347730" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects P-gp stability and localization.", "mechanism": "Modulates colchicine bioavailability and toxicity via drug efflux; inhibition increases colchicine exposure.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347769" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ABCA1 trafficking and function.", "mechanism": "Upregulated by colchicine nanoformulations, promoting cholesterol efflux and reducing vascular inflammation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12347769" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ligand binding and receptor stability.", "mechanism": "Downregulated by colchicine liposomes, reducing oxidized LDL uptake and foam cell formation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences receptor function.", "mechanism": "Downregulated by colchicine liposomes, limiting lipid uptake and plaque progression.", "protein": "SRA-1 (SCARA1)", "protein_enriched": { "function": "Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation", "gene_name": "PROCR", "glycan_count": 15, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G23719VF", "G27058EU", "G48414YA", "G55412XP", "G56784JY", "G59324HL", "G75983OB", "G81315DD", "G84452RH", "G00912UN", "G45395BF", "G57776ZS", "G90382BL", "G03612IF", "G49108TO" ], "uniprot_id": "Q9UNN8" }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "Glycosylation required for cytokine secretion.", "mechanism": "Colchicine inhibits NLRP3 inflammasome activation, blocking IL-1\u03b2 maturation and release.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "Colchicine suppresses IL-6 expression, reducing inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "medium", "disease": "Familial Mediterranean fever", "glycan_involvement": "Glycosylation required for cytokine secretion.", "mechanism": "Colchicine blocks NLRP3-mediated IL-18 maturation, reducing autoinflammatory attacks.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion.", "mechanism": "Colchicine microneedles suppress TNF-\u03b1 production, attenuating fibrosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347769" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation regulates CD44 ligand binding and tumor targeting.", "mechanism": "CD44-targeted liposomes deliver colchicine to tumor cells, enhancing antitumor efficacy.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347769" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation essential for P-selectin function and endothelial localization.", "mechanism": "Polymer nanoparticles targeting P-selectin facilitate delivery to inflamed endothelium.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347769" }, { "confidence": "high", "disease": "Non-thyroidal illness syndrome (NTIS)", "glycan_involvement": "TBG is a glycoprotein; glycosylation affects stability and hormone binding.", "mechanism": "TBG binds ~75% of circulating T4/T3, affecting total hormone levels and dialytic loss potential.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation modulates TBG half-life and function.", "mechanism": "Altered TBG levels may influence thyroid hormone availability in AKI patients.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "high", "disease": "Non-thyroidal illness syndrome (NTIS)", "glycan_involvement": "TSH is a glycoprotein; glycosylation is essential for secretion and receptor interaction.", "mechanism": "TSH levels remain normal or mildly decreased in NTIS despite low T3.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation affects TBG's hormone binding affinity.", "mechanism": "TBG levels influence total T4/T3 measurements in hypothyroidism diagnosis.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH glycosylation is required for biological activity.", "mechanism": "Elevated TSH is a hallmark of hypothyroidism.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Critical illness", "glycan_involvement": "Glycosylation status may change during acute phase responses.", "mechanism": "Critical illness may alter TBG levels, impacting thyroid hormone transport.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Critical illness", "glycan_involvement": "Glycosylation influences TSH stability and receptor binding.", "mechanism": "TSH levels may be suppressed or normal in critical illness, reflecting axis adaptation.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation maintains TBG's hormone binding under stress.", "mechanism": "In thyroid storm, TBG binding capacity may be overwhelmed, increasing free hormone fraction.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation required for TSH function.", "mechanism": "TSH is typically suppressed in thyroid storm.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12347796" }, { "confidence": "medium", "disease": "Non-thyroidal illness syndrome (NTIS)", "glycan_involvement": "Glycosylation modulates TBG's hormone binding and serum half-life.", "mechanism": "Altered TBG levels may contribute to changes in total thyroid hormone concentrations in NTIS.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "causal", "source_pmcid": "PMC12347796" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP is elevated in obesity, reflecting chronic low-grade inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates complement activation and clearance.", "mechanism": "C3 is increased in obesity, indicating complement system activation and inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation influences SAA solubility and aggregation.", "mechanism": "SAA is elevated in obesity, marking acute-phase response and systemic inflammation.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects haptoglobin's hemoglobin-binding and anti-inflammatory properties.", "mechanism": "Haptoglobin is increased in obesity, reflecting inflammatory status.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. 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Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation influences complement cascade activity.", "mechanism": "C5 is increased in obesity, indicating enhanced complement activation.", "protein": "Complement C5", "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation is critical for VCAM-1 cell adhesion and immune interactions.", "mechanism": "sVCAM-1 is higher in men and associated with increased immune cell recruitment and endothelial activation.", "protein": "Soluble vascular cell adhesion molecule-1 (sVCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Sialylated O-glycans mediate leukocyte binding and endothelial activation.", "mechanism": "E-selectin is lower in obese women, higher in men, reflecting sex differences in vascular inflammation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation modulates C1q immune complex recognition.", "mechanism": "C1q is increased in obesity, indicating activation of the classical complement pathway.", "protein": "Complement C1q", "relationship_type": "biomarker", "source_pmcid": "PMC12347797" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and secretion.", "mechanism": "APP is cleaved to produce amyloid beta peptides, which aggregate to form plaques in AD.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may modulate tau aggregation and phosphorylation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, leading to neuronal dysfunction.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status may affect GFAP stability and detection.", "mechanism": "Elevated GFAP in plasma/CSF reflects astrocyte activation and neuroinflammation in AD.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycosylation essential for secretion and function.", "mechanism": "Increased CHI3L1 in CSF/plasma correlates with tau pathology and neuroinflammation.", "protein": "Chitinase-3-like protein 1 (CHI3L1/YKL-40)", "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for TREM2 cell surface expression and shedding.", "mechanism": "Soluble TREM2 increases in CSF/plasma during microglial activation in AD.", "protein": "Triggering receptor expressed on myeloid cells 2 (TREM2)", "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences MCP-1 secretion and receptor binding.", "mechanism": "Elevated MCP-1 in blood associates with faster cognitive decline in AD.", "protein": "Monocyte chemoattractant protein-1 (MCP-1/CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect NfL solubility and release.", "mechanism": "Increased NfL in plasma/CSF reflects axonal degeneration in AD.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for function and ligand binding.", "mechanism": "Upregulated in neuronal-derived exosomes from AD patients; associated with endothelial dysfunction.", "protein": "Platelet glycoprotein Ib beta chain", "protein_enriched": { "function": "Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium", "gene_name": "GP1BB", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P13224" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Highly glycosylated; glycan changes may affect anti-inflammatory properties.", "mechanism": "Downregulated in exosomes from AD patients; may reflect altered inflammation.", "protein": "Alpha-1-acid glycoprotein 2", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and avai", "gene_name": "ORM2", "glycan_count": 148, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G05049YU", "G27947YN", "G35029YA", "G40906DZ", "G41247ZX", "G44753VC", "G45395BF", "G45504EY", "G57317CE", "G59626AS", "G70441OD", "G80479JV", "G86182NS", "G88382QE", "G90093AU", "G95865ZB", "G98559XP", "G06247RL", "G06356OH", "G10486CT", "G11115RO", "G11629QQ", "G12793SR", "G15169WU", "G20425TQ", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G47518TP", "G48414YA", "G50045TK", "G52527GH", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G66088HZ", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G85144OK", "G86752LQ", "G94917XT", "G99679NM", "G11911BT", "G67506FN", "G69834CE", "G82830MN", "G92081HT", "G95977AE", "G22310AV", "G33791AF", "G55412XP", "G84452RH", "G86795LJ", "G89205CJ", "G93656SY", "G01160VV", "G02528FI", "G05962QB", "G07810QS", "G08918WF", "G10819WX", "G13191RB", "G13910DJ", "G22572EH", "G28681TP", "G29545VG", "G29580WD", "G30221QT", "G30740WO", "G35541EV", "G37818NZ", "G40574BA", "G43669FQ", "G47012YE", "G49755GI", "G49955PK", "G50856PC", "G53075ES", "G56518TU", "G56770VP", "G57776ZS", "G63040RU", "G64751KD", "G66537LK", "G70232NH", "G70888PK", "G74381CZ", "G76868JS", "G77338BR", "G80075MS", "G81637OR", "G83633GK", "G86880BF", "G92135MA", "G93718GY", "G94665LC", "G95678HJ", "G99668VU", "G00814BW", "G04328BO", "G04920ZE", "G09811YI", "G14050KB", "G18938DW", "G19972YZ", "G22826KU", "G23863VK", "G29568VE", "G29857RC", "G30743QX", "G30769VJ", "G31544HA", "G35975NI", "G36191CD", "G36523TZ", "G37310RN", "G38738YC", "G40183VY", "G41690KS", "G41929NX", "G46449AK", "G50058RB", "G50329HB", "G56491QJ", "G64271PC", "G70894RY", "G70898AL", "G71560PC", "G77447DK", "G77582RK", "G85542EC", "G87108ET", "G88067KZ", "G88555GL", "G88756OE", "G90202LF", "G92793BY", "G93519WM", "G94536SD", "G94989HM", "G99683ND" ], "uniprot_id": "P19652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for ADAM10 trafficking and activity.", "mechanism": "ADAM10 acts as \u03b1-secretase, promoting non-amyloidogenic APP processing; downregulated in AD exosomes.", "protein": "A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347836" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "IGFBP1 is a glycoprotein; altered glycosylation may affect its stability and function in endometrial tissue.", "mechanism": "Reduced IGFBP1 expression in endometrial stromal cells from women with endometriosis is associated with impaired decidualization.", "protein": "IGFBP1", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "PRL is a glycoprotein; glycosylation affects secretion and receptor interaction.", "mechanism": "Lower PRL expression in endometriotic stromal cells correlates with defective decidualization and infertility.", "protein": "PRL", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "mPR\u03b2 is a membrane glycoprotein; glycosylation may regulate receptor localization and function.", "mechanism": "Decreased mPR\u03b2 expression in endometriotic tissue leads to impaired progesterone signaling and defective decidualization.", "protein": "mPR\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation of IGFBP1 modulates its binding to IGFs and tissue distribution.", "mechanism": "Low IGFBP1 levels in endometrial stromal cells are linked to implantation failure and infertility.", "protein": "IGFBP1", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation affects PRL's bioactivity and stability.", "mechanism": "Reduced PRL expression in endometrial stromal cells impairs decidualization and embryo implantation.", "protein": "PRL", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation may influence mPR\u03b2's membrane localization and signaling.", "mechanism": "mPR\u03b2 knockdown reduces expression of key decidualization markers, contributing to infertility.", "protein": "mPR\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12347855" }, { "confidence": "medium", "disease": "Recurrent pregnancy loss", "glycan_involvement": "Glycosylation may affect mPR\u03b2 stability and function in endometrial cells.", "mechanism": "Reduced mPR\u03b2 expression is observed in women with recurrent spontaneous abortions.", "protein": "mPR\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "medium", "disease": "Recurrent pregnancy loss", "glycan_involvement": "Altered glycosylation may impact IGFBP1 function in implantation.", "mechanism": "Defective decidualization and low IGFBP1 expression are associated with recurrent pregnancy loss.", "protein": "IGFBP1", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "medium", "disease": "Recurrent pregnancy loss", "glycan_involvement": "Glycosylation status may affect PRL's activity in the endometrium.", "mechanism": "Low PRL levels in decidual cells are linked to pregnancy loss due to poor endometrial receptivity.", "protein": "PRL", "relationship_type": "biomarker", "source_pmcid": "PMC12347855" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation may modulate mPR\u03b2's responsiveness to agonists.", "mechanism": "Activation of mPR\u03b2 by agonists (e.g., Org OD 02-0) can induce decidualization marker expression, suggesting therapeutic potential.", "protein": "mPR\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347855" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects secretion, stability, and receptor binding.", "mechanism": "Altered Reelin levels and cleavage fragments in CSF/blood correlate with AD progression; Reelin modulates tau phosphorylation and amyloid-\u03b2 metabolism.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347856" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Enhancing Reelin signaling protects against tau hyperphosphorylation and amyloid-\u03b2 toxicity, preserving synaptic integrity.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347856" }, { "confidence": "high", "disease": "Age-related macular degeneration", "glycan_involvement": "N-glycosylation influences ECM interactions and stability.", "mechanism": "Decreased Reelin in retina and ocular fluids associated with AMD severity; reflects ECM dysregulation and inflammation.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347856" }, { "confidence": "medium", "disease": "Age-related macular degeneration", "glycan_involvement": "N-glycosylation modulates ECM binding and anti-inflammatory activity.", "mechanism": "Reduced Reelin impairs ECM homeostasis, promotes drusen formation, and exacerbates inflammation and oxidative stress in the retina.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC12347856" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation required for vascular/endothelial interactions.", "mechanism": "Peripheral depletion of Reelin reduces neuroinflammation and leukocyte infiltration via endothelial modulation.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347856" }, { "confidence": "medium", "disease": "Crohn's Disease", "glycan_involvement": "N-glycosylation affects secretion and local activity.", "mechanism": "Upregulation of Reelin in colon protects against DSS-induced colitis; regulates epithelial migration and immune response.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "protective", "source_pmcid": "PMC12347856" }, { "confidence": "medium", "disease": "Autism", "glycan_involvement": "N-glycosylation essential for developmental function.", "mechanism": "Reduced Reelin during development linked to abnormal neuronal migration and neurodevelopmental deficits.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC12347856" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "N-glycosylation required for secretion and synaptic function.", "mechanism": "Decreased Reelin expression (e.g., via promoter hypermethylation) associated with cortical and hippocampal deficits.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC12347856" }, { "confidence": "low", "disease": "Arthritis", "glycan_involvement": "N-glycosylation impacts vascular interactions.", "mechanism": "Reelin modulates endothelial activation and leukocyte adhesion, influencing inflammatory processes.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347856" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates vascular binding and activity.", "mechanism": "Reelin promotes endothelial activation and vascular inflammation, contributing to disease progression.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347856" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "PSGs are heavily N-glycosylated; glycosylation mediates immune interactions and cell adhesion.", "mechanism": "cnLOH in 19q13.2\u201319q13.31 region (PSG cluster) is enriched in MRD-positive B-ALL, suggesting involvement in therapy resistance via immune modulation and angiogenesis.", "protein": "PSG gene family (PSG1\u2013PSG11)", "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "colorectal cancer", "glycan_involvement": "N-glycosylation required for cell surface localization and function.", "mechanism": "Promotes angiogenesis via SMAD4 interaction and upregulation of VEGFA and PDGF-AA.", "protein": "PSG9", "protein_enriched": { "function": "Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL", "gene_name": "LIP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P22394" }, "relationship_type": "causal", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "cervical cancer", "glycan_involvement": "N-glycosylation modulates cytokine interactions.", "mechanism": "Gene amplification and overexpression linked to immunosuppressive microenvironment (IL-10, TGF-\u03b2 upregulation).", "protein": "PSG1", "protein_enriched": { "function": "", "gene_name": "PSG1", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11464" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "low", "disease": "pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation affects trafficking and immune recognition.", "mechanism": "Expression and subcellular localization correlate with patient outcomes.", "protein": "PSG1", "protein_enriched": { "function": "", "gene_name": "PSG1", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11464" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "lung adenocarcinoma", "glycan_involvement": "N-glycosylation influences cell signaling and immune evasion.", "mechanism": "High expression associated with poor survival; linked to KRAS pathway alterations.", "protein": "PSG3, PSG7, PSG8", "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "N-glycosylation critical for adhesion and immune modulation.", "mechanism": "Involved in cell surface interactions at vascular wall; may modulate immune response and microenvironment.", "protein": "CEACAM1", "protein_enriched": { "function": "Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and also function", "gene_name": "CEACAM1", "glycan_count": 47, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22572EH", "G49108TO", "G57776ZS", "G80075MS", "G92275SC", "G00912UN", "G05724UK", "G06110VR", "G07246CJ", "G10819WX", "G14669DU", "G27947YN", "G28681TP", "G39188ZX", "G40926MX", "G49906RN", "G59626AS", "G70441OD", "G70619PT", "G79666IR", "G80920RR", "G86880BF", "G87661QW", "G41071NU", "G42124LM", "G23984SE", "G27058EU", "G75983OB", "G83229XP", "G84452RH", "G01650EU", "G02815KT", "G11870QZ", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G43089EG", "G59924QI", "G62765YT", "G64527OM", "G84225JN", "G92050GC", "G92406TI", "G95865ZB", "G25418HZ" ], "uniprot_id": "P13688" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "Metallothioneins are not classical glycoproteins; no direct glycan involvement.", "mechanism": "Deletion of 16q13 (metallothionein cluster) associated with poor prognosis and therapy resistance; impacts metal ion homeostasis and oxidative stress response.", "protein": "MT1A, MT2A, MT3", "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "acute myeloid leukemia (AML)", "glycan_involvement": "Not applicable.", "mechanism": "Promoter hypermethylation leads to inactivation; loss of tumor suppressor function.", "protein": "MT3", "protein_enriched": { "function": "Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro", "gene_name": "MT3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25713" }, "relationship_type": "causal", "source_pmcid": "PMC12347871" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "Glycosylation mediates PSG interaction with immune cells.", "mechanism": "PSGs promote regulatory T-cell differentiation via TGF-\u03b2, contributing to immune evasion and therapy resistance.", "protein": "PSG gene family", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347871" }, { "confidence": "low", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Cell adhesion molecule involved in vascular interactions and immune modulation.", "protein": "CEACAM8", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion in a calcium-independent manner (PubMed:11590190, PubMed:2022629, PubMed:8776764). Mediates heterophilic cell adhesion with other carcinoem", "gene_name": "CEACAM8", "glycan_count": 10, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G77547TA", "G23432EQ", "G05724UK", "G06110VR", "G14669DU", "G39188ZX", "G05962QB", "G35541EV", "G67164EE", "G93718GY" ], "uniprot_id": "P31997" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347871" }, { "confidence": "high", "disease": "Chronic Heart Failure", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Dapagliflozin inhibits SGLT2, improving prognosis in chronic heart failure by reducing glucose reabsorption and exerting diuretic and hemodynamic effects.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347874" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation affects SGLT2 stability and renal expression.", "mechanism": "SGLT2 inhibition reduces intraglomerular pressure and slows CKD progression.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347874" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates SGLT2 transporter activity.", "mechanism": "SGLT2 inhibitors lower blood glucose by blocking renal glucose reabsorption.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347874" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation is required for SGLT2 function in renal sodium handling.", "mechanism": "SGLT2 inhibition leads to osmotic diuresis and blood pressure reduction.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347874" }, { "confidence": "medium", "disease": "Acute Kidney Injury", "glycan_involvement": "Altered glycosylation may affect SGLT2-mediated renal responses.", "mechanism": "SGLT2 inhibition can cause an initial dip in eGFR, potentially increasing AKI risk in susceptible patients.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "causal", "source_pmcid": "PMC12347874" }, { "confidence": "medium", "disease": "Cardiorenal Syndrome", "glycan_involvement": "Glycosylation ensures proper SGLT2 function in the kidney-heart axis.", "mechanism": "SGLT2 inhibition improves cardiorenal outcomes by modulating hemodynamics and reducing renal stress.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347874" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Activation and ECM binding involve glycoprotein partners (e.g., LTBP, integrins).", "mechanism": "Promotes EMT, immune evasion, metastasis, and stromal remodeling via canonical and non-canonical signaling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Restoration alters \u03b21-integrin glycosylation, affecting adhesion/migration.", "mechanism": "Loss-of-function mutations drive tumorigenesis, EMT, and metastasis, especially in MSI-H CRC.", "protein": "TGFBR2", "protein_enriched": { "function": "Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transdu", "gene_name": "TGFBR2", "glycan_count": 12, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G13694XX", "G37881RL", "G38663NM", "G55412XP", "G56784JY", "G57888GL", "G62461SM", "G57321FI", "G11629QQ", "G22310AV", "G62765YT", "G80920RR" ], "uniprot_id": "P37173" }, "relationship_type": "causal", "source_pmcid": "PMC12347881" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Altered glycosylation by TGFBR2 restoration.", "mechanism": "Glycosylation changes modulate cell adhesion and migration, impacting metastatic potential.", "protein": "\u03b21-integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Not directly specified.", "mechanism": "Upregulated by TGF-\u03b2/USF2 axis, promotes EMT and correlates with metastasis and poor prognosis.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12347881" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "EGFR is a glycoprotein; glycosylation affects receptor function.", "mechanism": "Co-expression with TGF-\u03b2 correlates with poor prognosis and reduced survival.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not directly specified.", "mechanism": "TGF-\u03b21/FBXO3 axis degrades \u0394Np63\u03b1, promoting EMT and metastasis.", "protein": "\u0394Np63\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "Activation of latent TGF-\u03b2 by integrin \u03b1v\u03b26 (glycoprotein).", "mechanism": "Induced by TGF-\u03b2 via integrin \u03b1v\u03b26, mediates immune escape and resistance to cytotoxic T cells.", "protein": "SOX4", "protein_enriched": { "function": "Transcription factor that acts as a transcriptional activator (PubMed:24886874, PubMed:26543203). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional ", "gene_name": "SOX11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35716" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation affects stability and immune recognition.", "mechanism": "Upregulated by TGF-\u03b21 via Smad2, contributing to immune evasion and resistance to immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Chemoresistant cancer", "glycan_involvement": "Activation involves integrin \u03b1v\u03b21 (glycoprotein) and MMP9.", "mechanism": "Activated by NETs post-chemotherapy, induces EMT and resistance in metastatic breast cancer.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Immunotherapy-resistant cancer", "glycan_involvement": "TGFBR1 is a glycoprotein receptor.", "mechanism": "Inhibition (e.g., galunisertib) reverses TGF-\u03b2-mediated immune suppression and EMT, improving response to checkpoint inhibitors.", "protein": "TGFBR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347881" }, { "confidence": "high", "disease": "Pharmacoresistant Epilepsy", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Upregulated at BBB in SE, effluxes anti-seizure drugs, reducing efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347885" }, { "confidence": "high", "disease": "Status Epilepticus", "glycan_involvement": "N-glycosylation affects receptor binding and transport.", "mechanism": "Leakage into brain after BBB disruption, binds astrocytic TGF-\u03b2 receptor, triggers hyperexcitability.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates extracellular release and immune activation.", "mechanism": "Released by injured neurons, activates TLR signaling, perpetuates inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347885" }, { "confidence": "high", "disease": "Status Epilepticus", "glycan_involvement": "N-glycosylation required for secretion and receptor interaction.", "mechanism": "Promotes NMDA receptor phosphorylation, increases excitability, reduces GABA currents.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "high", "disease": "Status Epilepticus", "glycan_involvement": "Glycosylation influences receptor binding and stability.", "mechanism": "Upregulates AMPA receptors, triggers GABA receptor endocytosis, increases excitatory transmission.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects filament assembly and stability.", "mechanism": "Astroglial activation marker, correlates with SE severity and neuronal injury.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347885" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates extracellular release.", "mechanism": "Elevated in SE, reflects astrocyte activation and injury.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347885" }, { "confidence": "medium", "disease": "Status Epilepticus", "glycan_involvement": "N-glycosylation essential for complement activation.", "mechanism": "A1 astrocyte marker, promotes TRPV1 expression, reduces synaptic density.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "medium", "disease": "Epileptogenesis", "glycan_involvement": "N-glycosylation modulates cell adhesion and synaptic function.", "mechanism": "Controlled by TNF-\u03b1, regulates excitatory/inhibitory synapse development.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "medium", "disease": "Blood-Brain Barrier Disruption", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "Degrades basal lamina and tight junctions, promotes BBB breakdown and albumin extravasation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12347885" }, { "confidence": "high", "disease": "HER2-positive Breast Cancer", "glycan_involvement": "N-glycosylation modulates receptor dimerization and antibody binding.", "mechanism": "HER2 amplification/overexpression drives proliferation; targeted by trastuzumab and ADCs.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation affects cell surface localization and antibody recognition.", "mechanism": "High TROP2 expression associated with poor prognosis; targeted by sacituzumab govitecan ADC.", "protein": "TROP2 (EGP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 expression predicts response to immune checkpoint inhibitors.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Endocrine-resistant Breast Cancer", "glycan_involvement": "Glycosylation may affect receptor function and ligand binding.", "mechanism": "ESR1 mutations drive resistance to endocrine therapy; predictive for ER-targeting drugs.", "protein": "Estrogen Receptor alpha (ER\u03b1, ESR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "PARP1 inhibition induces synthetic lethality in BRCA1/2-deficient tumors.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may affect PI3K signaling complex formation.", "mechanism": "PIK3CA mutations predict response to PI3K inhibitors and resistance to chemotherapy.", "protein": "PI3K (PIK3CA)", "protein_enriched": { "function": "Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:", "gene_name": "PIK3CA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42336" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Secretory Breast Cancer", "glycan_involvement": "Glycosylation regulates receptor trafficking and signaling.", "mechanism": "NTRK fusion drives pathogenesis; targeted by larotrectinib/entrectinib.", "protein": "NTRK1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02583" }, "relationship_type": "causal", "source_pmcid": "PMC12347907" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "RB1 loss predicts resistance to CDK4/6 inhibitors.", "protein": "RB1", "protein_enriched": { "function": "Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcript", "gene_name": "RB1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50713DU", "G49108TO" ], "uniprot_id": "P06400" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347907" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "CDK4/6 inhibitors block cell cycle progression; efficacy depends on intact RB1.", "protein": "CDK4", "protein_enriched": { "function": "Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transi", "gene_name": "CDK4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11802" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347907" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "CCND1 amplification not predictive for CDK4/6 inhibitor response.", "protein": "Cyclin D1 (CCND1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347907" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "IL-23 is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "IL-23 activates Th17 cells, leading to neutrophilic infiltration and mucosal inflammation in UC.", "protein": "Interleukin-23 (IL-23)", "protein_enriched": { "function": "Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383). Released by antigen-presenting cells such as dendritic c", "gene_name": "IL23A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPF7" }, "relationship_type": "causal", "source_pmcid": "PMC12347990" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation of IL-23 may affect receptor binding and immune recognition.", "mechanism": "Blocking IL-23 reduces Th17 activation and neutrophil-driven inflammation.", "protein": "Interleukin-23 (IL-23)", "protein_enriched": { "function": "Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383). Released by antigen-presenting cells such as dendritic c", "gene_name": "IL23A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPF7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347990" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "As a monoclonal antibody, mirikizumab is glycosylated, which affects its stability and effector function.", "mechanism": "Mirikizumab neutralizes IL-23, leading to clinical and endoscopic improvement in UC patients with high neutrophilic infiltration.", "protein": "Mirikizumab (anti-IL-23 antibody)", "relationship_type": "therapeutic", "source_pmcid": "PMC12347990" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation status may influence IL-23 detection and function.", "mechanism": "High IL-23 activity correlates with increased neutrophilic infiltration (Geboes Grade 3.2/3.3), identifying active disease.", "protein": "Interleukin-23 (IL-23)", "protein_enriched": { "function": "Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383). Released by antigen-presenting cells such as dendritic c", "gene_name": "IL23A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPF7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347990" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation affects Kir4.1 trafficking and stability.", "mechanism": "Kir4.1 autoantibodies detected in MS; Kir4.1 loss impairs myelination and white matter integrity.", "protein": "Kir4.1", "protein_enriched": { "function": "May be responsible for potassium buffering action of glial cells in the brain (By similarity). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow in", "gene_name": "KCNJ10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P78508" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "N-glycosylation required for Kir4.1 membrane localization.", "mechanism": "Kir4.1 downregulation in oligodendrocytes impairs K+ buffering, contributing to ALS pathology.", "protein": "Kir4.1", "protein_enriched": { "function": "May be responsible for potassium buffering action of glial cells in the brain (By similarity). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow in", "gene_name": "KCNJ10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P78508" }, "relationship_type": "causal", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation modulates channel gating.", "mechanism": "Nav1.2 upregulated at demyelinated axons; involved in remyelination and axon-glia communication.", "protein": "Nav1.2", "protein_enriched": { "function": "Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a so", "gene_name": "SCN2A", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99250" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation affects channel function.", "mechanism": "Nav1.6 aggregates at nodes of regenerating myelin in MS lesions.", "protein": "Nav1.6", "protein_enriched": { "function": "Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively ", "gene_name": "SCN8A", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G83161QT", "G49108TO" ], "uniprot_id": "Q9UQD0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348010" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation required for channel surface expression.", "mechanism": "Cav1.2 deletion impairs OPC migration/proliferation; Cav antagonists improve outcomes in EAE.", "protein": "Cav1.2", "protein_enriched": { "function": "Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17224476, Pub", "gene_name": "CACNA1C", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q13936" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation modulates mechanosensitivity.", "mechanism": "Piezo1 downregulated in MS white matter; regulates OPC proliferation/migration.", "protein": "Piezo1", "protein_enriched": { "function": "Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (", "gene_name": "PIEZO1", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G41071NU", "G62765YT", "G67031OU", "G07246CJ", "G25079LO", "G27058EU", "G40574BA", "G70441OD", "G80920RR", "G90659AW" ], "uniprot_id": "Q92508" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348010" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation required for transporter function.", "mechanism": "NCX3 upregulated in chronic EAE; knockout worsens myelination and neurological deficits.", "protein": "NCX3", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6U6" }, "relationship_type": "protective", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "N-glycosylation affects channel gating.", "mechanism": "Kv inhibitor (4-aminopyridine) improves axonal conduction in ALS models.", "protein": "Kv1.3", "protein_enriched": { "function": "Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a", "gene_name": "KCNA3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P22001" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348010" }, { "confidence": "medium", "disease": "White Matter Pathology", "glycan_involvement": "N-glycosylation regulates receptor trafficking.", "mechanism": "GluA2 overexpression alters OPC proliferation/differentiation; region- and age-dependent effects.", "protein": "AMPAR (GluA2)", "protein_enriched": { "function": "Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), ", "gene_name": "GRIA2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P42262" }, "relationship_type": "causal", "source_pmcid": "PMC12348010" }, { "confidence": "high", "disease": "Traumatic CNS Injury", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "NMDAR antagonists (amantadine, memantine) reduce neurological disability and myelin damage.", "protein": "NMDAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348010" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "No direct glycosylation; regulates glycoprotein cytokine signaling.", "mechanism": "HDAC6 overexpression promotes pro-inflammatory signaling (AKT, MAPK, STAT3), keratinocyte hyperproliferation, and immune cell infiltration; inhibition ameliorates disease.", "protein": "HDAC6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and stability.", "mechanism": "Elevated IL-6 in psoriatic lesions; suppressed by HDAC6 inhibition.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "TNF-\u03b1 glycosylation modulates activity.", "mechanism": "TNF-\u03b1 drives inflammation; targeted by biologics and suppressed by HDAC6 inhibition.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Glycosylation affects secretion.", "mechanism": "IL-1\u03b2 is upregulated in psoriatic inflammation; suppressed by HDAC6 inhibition.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-17A produced by \u03b3\u03b4 T cells drives keratinocyte activation; suppressed by HDAC6 inhibition.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-23 promotes Th17/\u03b3\u03b4 T cell responses; suppressed by HDAC6 inhibition.", "protein": "IL-23", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348054" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Heavily glycosylated; glycosylation required for cell surface expression.", "mechanism": "F4/80 marks macrophage infiltration in psoriatic lesions; reduced by HDAC6 inhibition.", "protein": "F4/80", "protein_enriched": { "function": "May have regulatory role in cell division or differentiation in response to extracellular signals", "gene_name": "Skil", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q60665" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348054" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "O-glycosylation affects cross-linking and barrier function.", "mechanism": "Altered involucrin expression reflects abnormal keratinocyte differentiation in psoriasis; normalized by HDAC6 inhibition.", "protein": "Involucrin", "protein_enriched": { "function": "Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia", "gene_name": "IVL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07476" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348054" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Potential O-glycosylation modulates filament assembly.", "mechanism": "K17 overexpressed in hyperproliferative keratinocytes; reduced by HDAC6 inhibition.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348054" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Possible O-GlcNAcylation modulates activity.", "mechanism": "STAT3 activation drives keratinocyte proliferation and inflammation; suppressed by HDAC6 inhibition.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348054" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates NF-\u03baB signaling and cytokine secretion.", "mechanism": "Activation of NF-\u03baB pathway promotes hepatic inflammation and progression of MASLD.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects NLRP3 assembly and activation.", "mechanism": "NLRP3 inflammasome activation increases pro-inflammatory cytokines, driving MASLD progression.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated TNF-\u03b1 levels indicate hepatic inflammation and MASLD severity.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and activity.", "mechanism": "IL-6 promotes hepatic inflammation and fibrogenesis in MASLD.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "\u03b3GT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "Elevated \u03b3GT is a marker of liver injury and MASLD.", "protein": "\u03b3GT", "relationship_type": "biomarker", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated; glycan status influences serum levels.", "mechanism": "Increased AST levels reflect hepatocyte damage in MASLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT glycosylation modulates its stability and release.", "mechanism": "ALT elevation is indicative of liver cell injury in MASLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348136" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may regulate FOXO3 localization and activity.", "mechanism": "FOXO3 TT genotype associated with improved response to Mediterranean diet and reduced MASLD risk.", "protein": "FOXO3", "protein_enriched": { "function": "Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed", "gene_name": "FOXO3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G81295CK" ], "uniprot_id": "O43524" }, "relationship_type": "protective/therapeutic target", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation of insulin receptor is essential for function.", "mechanism": "Impaired insulin receptor signaling contributes to insulin resistance, a key MASLD risk factor.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Insulin and its receptor are glycoproteins; glycosylation affects signaling.", "mechanism": "Elevated HOMA-IR index reflects insulin resistance, predicting MASLD risk.", "protein": "HOMA-IR", "relationship_type": "biomarker", "source_pmcid": "PMC12348136" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "AChE is a glycoprotein; glycosylation affects stability and localization.", "mechanism": "AChE degrades acetylcholine; inhibition increases synaptic ACh, improving cognition in AD.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348157" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "A\u03b2 is derived from APP, a glycoprotein; glycosylation of APP modulates A\u03b2 production.", "mechanism": "A\u03b2 aggregation and fibrillization form amyloid plaques, driving AD pathology.", "protein": "Amyloid-beta peptide (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12348157" }, { "confidence": "high", "disease": "Cognitive dysfunction", "glycan_involvement": "Glycosylation influences AChE activity and localization in synapses.", "mechanism": "AChE inhibition restores acetylcholine levels, improving memory and learning.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348157" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation is essential for P-gp folding and transport function.", "mechanism": "P-gp effluxes A\u03b2 and drugs across the BBB; non-substrate drugs have better CNS retention.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "protective", "source_pmcid": "PMC12348157" }, { "confidence": "medium", "disease": "Drug toxicity", "glycan_involvement": "CYPs are glycoproteins; glycosylation affects enzyme stability and drug metabolism.", "mechanism": "CYP inhibition by drugs leads to accumulation and toxicity.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12348157" }, { "confidence": "high", "disease": "Cognitive dysfunction", "glycan_involvement": "APP glycosylation regulates A\u03b2 generation and aggregation propensity.", "mechanism": "A\u03b2 oligomers disrupt synaptic function, leading to memory deficits.", "protein": "Amyloid-beta peptide (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12348157" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Altered glycosylation may affect AChE levels in AD brain.", "mechanism": "Elevated AChE activity correlates with AD progression and cholinergic deficit.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348157" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation of APP influences A\u03b2 aggregation and clearance.", "mechanism": "Inhibition of A\u03b2 fibrillization reduces plaque formation and neurotoxicity.", "protein": "Amyloid-beta peptide (A\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348157" }, { "confidence": "medium", "disease": "Drug toxicity", "glycan_involvement": "Glycosylation is required for P-gp trafficking to the plasma membrane.", "mechanism": "P-gp prevents CNS accumulation of neurotoxic drugs.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "protective", "source_pmcid": "PMC12348157" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation modulates CYP enzyme activity and drug interactions.", "mechanism": "CYPs metabolize AD drugs; inhibition alters drug efficacy and safety.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348157" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune signaling.", "mechanism": "CRP levels are elevated in obesity and sleep apnea, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Insulin is glycosylated; glycan structure affects receptor binding and clearance.", "mechanism": "Hyperinsulinemia and increased HOMA-IR in obesity indicate insulin resistance.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation modulates receptor interaction and bioactivity.", "mechanism": "Leptin dysregulation contributes to appetite and weight gain in obesity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12348223" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects long-term glycemic control in diabetes and obesity.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "AST is glycosylated; glycan changes may affect enzyme stability.", "mechanism": "Elevated AST indicates hepatic dysfunction in obesity.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "ALT glycosylation may influence enzyme activity.", "mechanism": "ALT elevation signals liver injury in obese patients.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Lipoproteins are glycosylated; glycan patterns affect clearance and atherogenicity.", "mechanism": "Dyslipidemia in obesity increases cardiovascular risk.", "protein": "Total cholesterol (LDL/HDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Chronic venous insufficiency", "glycan_involvement": "Glycosylation of apolipoproteins modulates lipoprotein metabolism.", "mechanism": "Hypertriglyceridemia contributes to vascular dysfunction in obesity.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12348223" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "GLP-1 is glycosylated; glycan modifications affect stability and receptor activation.", "mechanism": "GLP-1 analogs are used to treat obesity by modulating appetite and insulin secretion.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348223" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "CRP glycosylation may influence neuroinflammatory signaling.", "mechanism": "Elevated CRP is associated with increased risk of depression in obese patients.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12348223" }, { "confidence": "high", "disease": "Inflammatory disorders (sepsis, fever)", "glycan_involvement": "N-glycosylation (5 sites) modulates AGP's immune and pharmacokinetic properties.", "mechanism": "AGP levels rise during inflammation, modulate immune responses, and transport tryptophan catabolites (serotonin, melatonin).", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation (2 sites) impacts iron transport and receptor interactions.", "mechanism": "TF levels reflect iron status and protein nutrition; glycosylation affects iron binding and immune modulation.", "protein": "Transferrin (TF)", "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Retinoid deficiency", "glycan_involvement": "Minor N-glycosylation affects stability and renal clearance.", "mechanism": "RBP transports retinol; low levels indicate deficiency and impaired immune function.", "protein": "Retinol-binding protein (RBP)", "protein_enriched": { "function": "Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans ret", "gene_name": "RBP4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02753" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Protein malnutrition (Kwashiorkor, Marasmus)", "glycan_involvement": "None (not glycosylated).", "mechanism": "TTR plasma levels reflect lean body mass and protein status; low in malnutrition.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Inflammatory disorders (sepsis, fever)", "glycan_involvement": "None (not glycosylated).", "mechanism": "CRP rises rapidly in acute inflammation; synthesis depends on tryptophan availability.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "medium", "disease": "Cancer (various neoplasms)", "glycan_involvement": "Altered N-glycosylation modulates AGP's function in cancer.", "mechanism": "AGP glycosylation patterns change in cancer, affecting immune evasion and drug binding.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "medium", "disease": "Acute infections", "glycan_involvement": "N-glycosylation modulates TF's immune interactions.", "mechanism": "TF levels decrease in infection/inflammation; glycosylation affects immune response.", "protein": "Transferrin (TF)", "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Neurodegenerative disorders (Alzheimer's, Parkinson's, Huntington's)", "glycan_involvement": "None.", "mechanism": "TTR binds and neutralizes amyloid-beta oligomers, limiting neurotoxicity; plasma/CSF TTR reflects disease progression.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "medium", "disease": "Immune dysfunction (NK/T-cell apoptosis)", "glycan_involvement": "N-glycosylation critical for immunomodulatory activity.", "mechanism": "AGP modulates immune cell function; glycosylation affects cytokine interactions and immune suppression.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal/modulatory", "source_pmcid": "PMC12348287" }, { "confidence": "medium", "disease": "Acute infections", "glycan_involvement": "N-glycosylation affects renal clearance.", "mechanism": "RBP and retinol leak in urine during infection; low plasma RBP indicates impaired retinoid delivery and immune defense.", "protein": "Retinol-binding protein (RBP)", "protein_enriched": { "function": "Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans ret", "gene_name": "RBP4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02753" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348287" }, { "confidence": "high", "disease": "Steatotic Liver Disease (SLD)", "glycan_involvement": "Glycation of hemoglobin is a direct glycan modification.", "mechanism": "Elevated HbA1c reflects impaired glucose metabolism, a risk factor for SLD.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "AST is glycosylated, affecting its stability and serum levels.", "mechanism": "Elevated AST indicates liver injury associated with hepatic steatosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "ALT glycosylation may influence its secretion and activity.", "mechanism": "Elevated ALT is a marker of hepatocellular injury in steatosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "\u03b3-GT is glycosylated, which affects its enzymatic activity.", "mechanism": "Elevated \u03b3-GT is associated with oxidative stress and liver dysfunction in steatosis.", "protein": "\u03b3-glutamyltransferase (\u03b3-GT)", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Steatotic Liver Disease (SLD)", "glycan_involvement": "LDL particles are glycosylated, influencing receptor binding and clearance.", "mechanism": "Elevated LDL-C is linked to metabolic dysfunction and SLD risk.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Steatotic Liver Disease (SLD)", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties.", "mechanism": "Low HDL-C is a risk factor for SLD and metabolic syndrome.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "Elevated HbA1c is associated with increased CVD risk in SLD patients.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "LDL glycosylation affects its atherogenicity.", "mechanism": "High LDL-C promotes atherosclerosis, increasing CVD risk in SLD.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation modulates \u03b3-GT activity and stability.", "mechanism": "Elevated \u03b3-GT is linked to oxidative stress and renal dysfunction in metabolic disease.", "protein": "\u03b3-glutamyltransferase (\u03b3-GT)", "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated SLD", "glycan_involvement": "Glycosylation affects AST serum levels.", "mechanism": "Elevated AST is a marker of liver injury in metabolic SLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348315" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "Activation by tirzepatide improves hepatic insulin sensitivity and reduces steatosis.", "protein": "GIP receptor", "protein_enriched": { "function": "Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis a", "gene_name": "Tpi1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48500" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348380" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates receptor stability and signaling.", "mechanism": "Activation by tirzepatide enhances glucose disposal and reduces hepatic fat.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Upregulated by ketogenic diet, promotes hepatic lipid catabolism and mitochondrial biogenesis.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation essential for multimerization and function.", "mechanism": "Increased by GIP receptor activation, improves lipid partitioning and reduces inflammation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may regulate subcellular localization.", "mechanism": "Activated by LEKT and tirzepatide, promotes autophagy and lipid oxidation.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "medium", "disease": "Steatohepatitis", "glycan_involvement": "Glycosylation influences inflammasome assembly.", "mechanism": "Inflammasome activation drives hepatic inflammation; inhibited by ketone bodies.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12348380" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect nuclear localization.", "mechanism": "Activated by tirzepatide and LEKT, enhances mitochondrial function and redox balance.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation may modulate DNA binding.", "mechanism": "Activated by ketogenic diet, increases fatty acid oxidation and reduces steatosis.", "protein": "PPAR-\u03b1", "protein_enriched": { "function": "Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethano", "gene_name": "PPARA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07869" }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "low", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "Regulates bile acid homeostasis and inhibits fibrotic remodeling.", "protein": "FXR", "protein_enriched": { "function": "Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in", "gene_name": "NR1H4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96RI1" }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation may regulate protein stability.", "mechanism": "Promotes mitochondrial biogenesis and metabolic flexibility.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "protective", "source_pmcid": "PMC12348380" }, { "confidence": "high", "disease": "Neurotoxicity", "glycan_involvement": "Glycosylation affects trafficking and function at BBB.", "mechanism": "Efflux of doxorubicin at the blood-brain barrier limits neurotoxicity.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "protective", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Nephrotoxicity", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated clusterin in urine/serum indicates renal injury after doxorubicin.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Nephrotoxicity", "glycan_involvement": "Glycosylation modulates anti-inflammatory properties.", "mechanism": "Increased AGP levels reflect inflammation and renal damage.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Nephrotoxicity", "glycan_involvement": "Glycosylation essential for secretion and renal targeting.", "mechanism": "NGAL upregulation signals acute kidney injury post-doxorubicin.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation regulates cell adhesion and immune response.", "mechanism": "ICAM1 upregulated in liver after doxorubicin, marking inflammation.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation required for endothelial binding.", "mechanism": "VCAM1 increased in hepatic tissue, indicating inflammatory injury.", "protein": "VCAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "MCP-1 upregulated in liver after doxorubicin, mediates monocyte recruitment.", "protein": "MCP-1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation modulates enzymatic activity.", "mechanism": "CD38 downregulated in liver after doxorubicin, associated with NAD+ deficiency.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Cardiotoxicity", "glycan_involvement": "Glycosylation influences nanoparticle formation and drug delivery.", "mechanism": "Albumin nanoparticles reduce doxorubicin-induced cardiotoxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates integrin ligand binding.", "mechanism": "Targeted delivery of doxorubicin via RGD-modified nanoparticles to integrin \u03b1v\u03b23-expressing tumor cells.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348484" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "Avidin is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "Avidin binds biotin tightly, forming immunogenic biotin\u2013avidin complexes that can act as allergens.", "protein": "Avidin", "protein_enriched": { "function": "The biological function of avidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of avidin)", "gene_name": "AVD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80005YU", "G81295CK" ], "uniprot_id": "P02701" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "medium", "disease": "Allergy", "glycan_involvement": "Streptavidin is a glycoprotein; glycosylation may modulate immune response.", "mechanism": "Streptavidin\u2013biotin complexes used in diagnostics can be immunogenic and interfere with allergy testing.", "protein": "Streptavidin", "protein_enriched": { "function": "The biological function of streptavidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of streptavidin)", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22629" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "IgE is a glycoprotein; glycosylation affects stability and function.", "mechanism": "IgE is measured in allergy diagnostics; biotin interference can cause false results.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12348524" }, { "confidence": "high", "disease": "Biotin deficiency", "glycan_involvement": "Glycosylation of avidin may affect biotin binding.", "mechanism": "Avidin in raw egg white binds dietary biotin, causing deficiency and skin/hair disorders.", "protein": "Avidin", "protein_enriched": { "function": "The biological function of avidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of avidin)", "gene_name": "AVD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80005YU", "G81295CK" ], "uniprot_id": "P02701" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates IgE function and detection.", "mechanism": "IgE levels are used to diagnose asthma; biotin interference in assays can affect accuracy.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12348524" }, { "confidence": "medium", "disease": "Allergy", "glycan_involvement": "Potential glycosylation may affect enzyme stability.", "mechanism": "HCS biotinylates carboxylases; defects can disrupt immune homeostasis, predisposing to allergy.", "protein": "Holocarboxylase synthetase (HCS)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EP", "gene_name": "NHLRC1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6VVB1" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "medium", "disease": "Allergy", "glycan_involvement": "BT is glycosylated; glycosylation affects activity.", "mechanism": "BT releases biotin from proteins; deficiency may impair immune regulation, increasing allergy risk.", "protein": "Biotinidase (BT)", "protein_enriched": { "function": "Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation", "gene_name": "BTD", "glycan_count": 63, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G02815KT", "G04854VP", "G08918WF", "G10486CT", "G22572EH", "G26330YA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G37881RL", "G40574BA", "G41247ZX", "G43669FQ", "G45395BF", "G48414YA", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G74381CZ", "G80920RR", "G83460ZZ", "G90659AW", "G94470IW", "G95865ZB", "G06247RL", "G33791AF", "G45495MK", "G47737VJ", "G56784JY", "G70232NH", "G75983OB", "G81263BG", "G84452RH", "G34989PA", "G43734MM", "G47518TP", "G92275SC", "G08796TW", "G11115RO", "G15169WU", "G22310AV", "G23719VF", "G28622IK", "G36379GD", "G39188ZX", "G52527GH", "G56518TU", "G69834CE", "G70888PK", "G72790NZ", "G76868JS", "G86880BF", "G88374WZ", "G94917XT", "G95678HJ", "G05933EN", "G50282JC", "G65344XH", "G88891KO", "G49108TO" ], "uniprot_id": "P43251" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "medium", "disease": "Nickel allergy", "glycan_involvement": "Glycosylation affects IgE function.", "mechanism": "IgE and IL-1\u03b2 elevated in biotin-deficient mice with nickel allergy.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12348524" }, { "confidence": "medium", "disease": "Atopic dermatitis", "glycan_involvement": "Glycosylation modulates IgE.", "mechanism": "IgE levels used in diagnosis; biotin interference may affect test results.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12348524" }, { "confidence": "low", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylation may influence immunogenicity.", "mechanism": "Avidin\u2013biotin complexes may trigger immune responses, potentially contributing to autoimmunity.", "protein": "Avidin", "protein_enriched": { "function": "The biological function of avidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of avidin)", "gene_name": "AVD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80005YU", "G81295CK" ], "uniprot_id": "P02701" }, "relationship_type": "causal", "source_pmcid": "PMC12348524" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and A\u03b2 generation.", "mechanism": "Abnormal metabolism of APP leads to accumulation of A\u03b2 1-42, triggering AD pathology.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Derived from glycosylated APP; glycosylation state influences aggregation.", "mechanism": "A\u03b2 1-42 aggregates form plaques, induce ROS, neuroinflammation, and neuronal apoptosis.", "protein": "A\u03b2 1-42 (Amyloid-beta 1-42)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Indirect via APP glycosylation.", "mechanism": "A\u03b2 1-42 triggers NF-\u03baB activation, increasing inflammatory cytokines.", "protein": "A\u03b2 1-42 (Amyloid-beta 1-42)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Neuronal apoptosis", "glycan_involvement": "Indirect via APP glycosylation.", "mechanism": "A\u03b2 1-42 increases Bax, decreases Bcl-2, leading to mitochondrial apoptosis.", "protein": "A\u03b2 1-42 (Amyloid-beta 1-42)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Memory impairment", "glycan_involvement": "Indirect via APP glycosylation.", "mechanism": "A\u03b2 1-42-induced cytotoxicity impairs synaptic function and memory.", "protein": "A\u03b2 1-42 (Amyloid-beta 1-42)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Not directly glycosylated; regulated by upstream glycoprotein signaling.", "mechanism": "NF-\u03baB upregulated by A\u03b2 1-42, mediates inflammatory gene expression.", "protein": "NF-\u03baB (p50/p65)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348729" }, { "confidence": "medium", "disease": "Neuronal apoptosis", "glycan_involvement": "Not a glycoprotein; regulated by glycoprotein-mediated pathways.", "mechanism": "Bcl-2 downregulated by A\u03b2 1-42, promoting apoptosis.", "protein": "Bcl-2", "relationship_type": "biomarker", "source_pmcid": "PMC12348729" }, { "confidence": "medium", "disease": "Neuronal apoptosis", "glycan_involvement": "Not a glycoprotein; regulated by glycoprotein-mediated pathways.", "mechanism": "Bax upregulated by A\u03b2 1-42, promoting apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Memory impairment", "glycan_involvement": "APP glycosylation modulates A\u03b2 production and toxicity.", "mechanism": "APP-derived A\u03b2 1-42 impairs synaptic function, leading to memory loss.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12348729" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Therapeutic effect modulates downstream of glycoprotein aggregation.", "mechanism": "GOEs/AVNs reduce A\u03b2 1-42-induced inflammation and oxidative stress.", "protein": "A\u03b2 1-42 (Amyloid-beta 1-42)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348729" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "Glycosylation required for ABCB1 membrane localization and function.", "mechanism": "EGCG induces ABCB1, increasing drug efflux and reducing drug exposure.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "Glycosylation affects OATP1A2 trafficking and substrate specificity.", "mechanism": "EGCG inhibits OATP1A2, reducing intestinal absorption of drugs (e.g., fexofenadine).", "protein": "OATP1A2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "high", "disease": "Idiopathic pulmonary fibrosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 secretion and receptor binding.", "mechanism": "EGCG inhibits TGF-\u03b21 signaling, attenuating profibrotic and pro-inflammatory pathways.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Obesity-related precocious puberty", "glycan_involvement": "EGFR glycosylation affects ligand binding and downstream signaling.", "mechanism": "EGCG modulates EGFR signaling, impacting lipid metabolism and hormonal regulation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may regulate STAT3 stability and localization.", "mechanism": "EGCG inhibits STAT3 phosphorylation, reducing proliferation and inflammation.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Acrylamide toxicity", "glycan_involvement": "Glycosylation may affect enzyme activity and substrate specificity.", "mechanism": "EGCG promotes glutathione conjugation and excretion of acrylamide metabolites.", "protein": "Glutathione S-transferase", "relationship_type": "protective", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Obesity-related precocious puberty", "glycan_involvement": "IGF1 glycosylation affects receptor interaction and stability.", "mechanism": "EGCG modulates IGF1 signaling, influencing metabolic and endocrine pathways.", "protein": "IGF1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation critical for ABCB1 drug transport function.", "mechanism": "EGCG modulates ABCB1, potentially affecting chemotherapeutic drug resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Glycosylation influences TGF-\u03b21 activity in tissue repair.", "mechanism": "Topical EGCG reduces inflammation and tissue damage via TGF-\u03b21 pathway modulation.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "medium", "disease": "Radiation-induced dermatitis", "glycan_involvement": "Glycosylation may affect STAT3-mediated skin responses.", "mechanism": "EGCG reduces inflammatory signaling, improving skin healing after radiotherapy.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348855" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Inhibition of N-glycan trimming in intestine and ER.", "mechanism": "DNJ inhibits \u03b1-glucosidase I/II, reducing carbohydrate digestion and postprandial hyperglycemia.", "protein": "\u03b1-glucosidase I/II (GANAB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348909" }, { "confidence": "high", "disease": "Viral infections (HIV-1, DENV, PEDV, SARS-CoV-2)", "glycan_involvement": "Blocks N-glycan processing on viral envelope proteins.", "mechanism": "DNJ inhibits host ER \u03b1-glucosidases, disrupting viral glycoprotein folding and virion assembly.", "protein": "\u03b1-glucosidase I/II (GANAB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348909" }, { "confidence": "high", "disease": "Viral infections (HIV-1, DENV, PEDV, SARS-CoV-2)", "glycan_involvement": "N-glycosylation of envelope proteins is essential for virion maturation.", "mechanism": "Proper glycosylation required for infectivity; DNJ-induced misfolding reduces infectivity.", "protein": "Viral envelope glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Indirect; glycosylation status may affect receptor function.", "mechanism": "DNJ activates IRS1/PI3K/Akt signaling, improving insulin sensitivity and glucose uptake.", "protein": "IRS1/PI3K/Akt pathway", "relationship_type": "protective", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Indirect; GSK-3\u03b2 may regulate glycoprotein signaling.", "mechanism": "DNJ modulates GSK-3\u03b2, increasing muscle glycogen content.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "protective", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "BDNF is a glycoprotein; glycosylation affects stability and function.", "mechanism": "DNJ enhances BDNF signaling, reduces \u03b2-amyloid deposition and neuroinflammation.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Cancer (melanoma, colorectal)", "glycan_involvement": "MMPs are glycoproteins; glycosylation modulates activity.", "mechanism": "DNJ inhibits MMP-2/9 activity, reducing metastasis.", "protein": "MMP-2/9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Collagen I is glycosylated; glycosylation affects fibrosis.", "mechanism": "DNJ reduces collagen I expression, ameliorating liver fibrosis.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "SOD2 is glycosylated; glycosylation affects enzyme stability.", "mechanism": "DNJ upregulates SOD2, reducing oxidative stress.", "protein": "SOD2", "relationship_type": "protective", "source_pmcid": "PMC12348909" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Glycosylation of surface proteins is key for biofilm formation.", "mechanism": "DNJ inhibits biofilm formation by targeting glycoprotein-mediated adhesion.", "protein": "Streptococcus mutans surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348909" }, { "confidence": "high", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Heavily glycosylated; glycosylation affects stability and trafficking.", "mechanism": "High LAMP3 expression is associated with poor prognosis and promotes metastasis.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Overexpression promotes metastasis and poor survival.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "causal", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Cancer-related malnutrition/cachexia", "glycan_involvement": "Binds \u03b2-galactoside glycans on cell surfaces, modulating cell signaling.", "mechanism": "Promotes muscle regeneration and repair, associated with muscle mass gain.", "protein": "Galectin-1 (Gal-1)", "relationship_type": "protective", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Lectin binding to glycan structures is essential for activity.", "mechanism": "Improves muscle function and sarcolemma integrity.", "protein": "Galectin-1 (Gal-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Cancer-related malnutrition/cachexia", "glycan_involvement": "Extensive O-glycosylation; glycan chains mediate immune evasion.", "mechanism": "Elevated levels indicate aggressive inflammation and poor muscle mass response.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "N-glycosylation affects receptor stability and signaling.", "mechanism": "High soluble IL12RB1 predicts poor muscle mass gain and chronic inflammation.", "protein": "IL12RB1", "protein_enriched": { "function": "Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. ", "gene_name": "IL12RB1", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P42701" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "medium", "disease": "Cancer-related malnutrition/cachexia", "glycan_involvement": "Glycosylation modulates receptor binding and apoptotic activity.", "mechanism": "High TRAIL levels indicate increased inflammation and muscle catabolism.", "protein": "TRAIL", "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "medium", "disease": "Cancer-related malnutrition/cachexia", "glycan_involvement": "Glycosylation may affect secretion and immune modulation.", "mechanism": "Elevated ARG1 is linked to tumor progression, immune suppression, and poor muscle response.", "protein": "ARG1", "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "medium", "disease": "Cancer-related malnutrition/cachexia", "glycan_involvement": "N-glycosylation required for secretion and receptor interaction.", "mechanism": "High baseline PGF predicts poor muscle mass response; may act as compensatory growth signal.", "protein": "PGF", "protein_enriched": { "function": "Growth factor active in angiogenesis and endothelial cell growth, stimulating their proliferation and migration. It binds to the receptor FLT1/VEGFR-1. Isoform PlGF-2 binds NRP1/neuropilin-1 and NRP2/", "gene_name": "PGF", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "medium", "disease": "Chronic inflammation/autoimmune diseases", "glycan_involvement": "N-glycosylation modulates ligand binding and immune signaling.", "mechanism": "Elevated soluble CD28 associated with inflammaging and immune dysregulation.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348936" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation affects membrane localization and function.", "mechanism": "URAT1 mediates uric acid reabsorption; inhibition lowers serum urate.", "protein": "URAT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation modulates transporter activity.", "mechanism": "GLUT9 facilitates uric acid reabsorption; downregulation promotes uric acid excretion.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation required for proper trafficking and function.", "mechanism": "ABCG2 promotes uric acid secretion; upregulation enhances uric acid clearance.", "protein": "ABCG2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348965" }, { "confidence": "medium", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation influences substrate specificity and stability.", "mechanism": "OAT1 mediates urate salt secretion; upregulation increases uric acid excretion.", "protein": "OAT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348965" }, { "confidence": "medium", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "OAT3 facilitates urate salt secretion; upregulation increases uric acid excretion.", "protein": "OAT3", "protein_enriched": { "function": "Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endog", "gene_name": "SLC22A7", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G62765YT" ], "uniprot_id": "Q9Y694" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Kidney injury", "glycan_involvement": "Glycosylation impacts protein stability and pathogenicity.", "mechanism": "Upregulation leads to urate accumulation and renal damage.", "protein": "URAT1", "relationship_type": "causal", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Kidney injury", "glycan_involvement": "Glycosylation modulates transporter activity.", "mechanism": "Increased GLUT9 expression promotes urate retention and kidney injury.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "causal", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Kidney injury", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Upregulation of ABCG2 reduces urate accumulation and protects renal tissue.", "protein": "ABCG2", "relationship_type": "protective", "source_pmcid": "PMC12348965" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Impaired uric acid excretion via URAT1 contributes to gout pathogenesis.", "protein": "URAT1", "relationship_type": "causal", "source_pmcid": "PMC12348965" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation influences disease-related transporter activity.", "mechanism": "GLUT9-mediated urate reabsorption exacerbates CKD progression.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "causal", "source_pmcid": "PMC12348965" }, { "confidence": "high", "disease": "Antiphospholipid antibody syndrome", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Autoantibodies against \u03b22 glycoprotein 1 are used to diagnose antiphospholipid syndrome, which can co-occur with SLE/NPSLE.", "protein": "\u03b22 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Anti-\u03b22 glycoprotein 1 antibodies are measured in SLE patients to assess risk of thrombosis.", "protein": "\u03b22 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Neuropsychiatric systemic lupus erythematosus (NPSLE)", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for function and stability.", "mechanism": "Low C3 levels reflect complement activation and are associated with NPSLE pathogenesis via vascular/endothelial injury.", "protein": "Complement component C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 98, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49955PK", "G69834CE", "G95678HJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10471FG", "G10486CT", "G11115RO", "G14260UH", "G14972EH", "G15664MX", "G17208MA", "G20312EM", "G23294PN", "G23453IV", "G23719VF", "G26330YA", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G32104JU", "G33609NS", "G34029GR", "G34730YF", "G36442WJ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G42124LM", "G46503DX", "G46691LC", "G48414YA", "G49018RC", "G50282JC", "G55220VL", "G57317CE", "G57776ZU", "G59626AS", "G60145BJ", "G61302NC", "G62765YT", "G63041LO", "G64527OM", "G65000LJ", "G65184UU", "G66538GV", "G66676MI", "G67324HN", "G68490OW", "G70101JE", "G70160EA", "G70441OD", "G70619PT", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G76295SF", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84349RE", "G87661QW", "G90575OW", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G96091TT", "G96430BV", "G99679NM", "G22768VO", "G30769VJ", "G31544HA", "G70375MX", "G72398FA", "G78790NZ", "G86234IN", "G90093AU", "G43417UB", "G40702WU", "G49108TO", "G68668TB", "G83161QT" ], "uniprot_id": "P01024" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12349068" }, { "confidence": "medium", "disease": "Neuropsychiatric systemic lupus erythematosus (NPSLE)", "glycan_involvement": "C4 glycosylation is required for complement activation.", "mechanism": "Low C4 levels are associated with SLE activity and may be lower in diffuse NPSLE.", "protein": "Complement component C4", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling ", "gene_name": "C4A", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G81006GJ", "G29931IJ", "G43417UB", "G74722FL", "G00912UN", "G02886BB", "G06110VR", "G06356OH", "G08146BT", "G22310AV", "G37868ZX", "G42358LZ", "G45495MK", "G48414YA", "G59626AS", "G64527OM", "G70101JE", "G71146HJ", "G75983OB", "G81263BG", "G82830MN", "G84452RH", "G88374WZ", "G49108TO", "G11870QZ", "G11911BT", "G14994KB", "G22768VO", "G50045TK", "G54612UD", "G63381RX", "G80223IX", "G83460ZZ", "G29068FM", "G01650EU", "G02815KT", "G05724UK", "G23294PN", "G31544HA", "G31852PQ", "G39188ZX", "G39619TI", "G41247ZX", "G46503DX", "G62765YT", "G62894KT", "G80920RR" ], "uniprot_id": "P0C0L4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Neuropsychiatric systemic lupus erythematosus (NPSLE)", "glycan_involvement": "Assay reflects activity of multiple glycoprotein complement components.", "mechanism": "CH50 reflects overall complement activity; lower levels indicate complement consumption in NPSLE.", "protein": "CH50 (complement activity)", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "medium", "disease": "Neuropsychiatric systemic lupus erythematosus (NPSLE)", "glycan_involvement": "Osteopontin is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "Elevated osteopontin in CSF is associated with NPSLE activity and decreases with treatment.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Antiphospholipid antibody syndrome", "glycan_involvement": "Target \u03b22 glycoprotein 1, a glycoprotein antigen.", "mechanism": "Anticardiolipin antibodies are diagnostic for antiphospholipid syndrome, often present in SLE/NPSLE.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Antiphospholipid antibody syndrome", "glycan_involvement": "Targets glycoprotein complexes (e.g., \u03b22 glycoprotein 1).", "mechanism": "Lupus anticoagulant is an autoantibody associated with thrombosis in SLE/NPSLE.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "medium", "disease": "Neuropsychiatric systemic lupus erythematosus (NPSLE)", "glycan_involvement": "Glycosylation modulates immune complex formation.", "mechanism": "Anti-\u03b22 glycoprotein 1 antibodies are measured in NPSLE patients to assess risk of neurovascular events.", "protein": "\u03b22 glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects osteopontin's immunomodulatory function.", "mechanism": "Osteopontin levels reflect inflammatory activity in SLE.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12349068" }, { "confidence": "high", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Chitinase is a glycoprotein; glycosylation may affect stability and activity.", "mechanism": "Degrades fungal cell wall chitin, enhancing maize resistance.", "protein": "Chitinase 1 (Zm00001d032946)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "high", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Likely glycosylated for membrane localization/function.", "mechanism": "Increases epidermal wax thickness, forming a physical barrier to fungal entry.", "protein": "Fatty acid elongate (Zm00001d032948)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Aux/IAA proteins may be glycosylated, affecting stability.", "mechanism": "Regulates auxin signaling; suppression of auxin pathway enhances resistance.", "protein": "Aux/IAA family protein IAA9 (Zm00001d018414)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "GATA factors can be glycosylated, influencing DNA binding.", "mechanism": "Regulates immune gene expression via SA signaling.", "protein": "GATA8 transcription factor (Zm00001d018421)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Glycosylation may modulate transcription factor activity.", "mechanism": "Regulates stress and defense responses, including ethylene signaling.", "protein": "AP2-EREBP transcription factor (Zm00001d020043)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Glycosylation likely required for membrane fusion and trafficking.", "mechanism": "Regulates vesicle trafficking for defense compound delivery.", "protein": "SNARE-interacting protein KEULE (Zm00001d004159)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "low", "disease": "Corn smut (Ustilago maydis infection)", "glycan_involvement": "Glycosylation critical for stress response function.", "mechanism": "Responds to biotic/abiotic stress, possibly involved in defense.", "protein": "Plant glycoprotein (Zm00001d036771)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Fusarium ear rot", "glycan_involvement": "Glycosylation may enhance enzyme activity.", "mechanism": "Likely degrades Fusarium cell wall chitin, contributing to resistance.", "protein": "Chitinase 1 (Zm00001d032946)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "medium", "disease": "Gibberella stalk rot", "glycan_involvement": "Glycosylation may affect membrane association.", "mechanism": "Strengthens physical barrier against stalk rot pathogens.", "protein": "Fatty acid elongate (Zm00001d032948)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "low", "disease": "Gray leaf spot", "glycan_involvement": "Glycosylation may modulate transcriptional activity.", "mechanism": "Regulates immune gene expression in response to fungal infection.", "protein": "GATA8 transcription factor (Zm00001d018421)", "relationship_type": "protective", "source_pmcid": "PMC12349571" }, { "confidence": "high", "disease": "Classical Hodgkin lymphoma (cHL)", "glycan_involvement": "CD30 is a glycoprotein; glycosylation affects its cell surface expression and antibody recognition.", "mechanism": "CD30 is highly expressed on Hodgkin/Reed-Sternberg cells and used for diagnosis and targeted therapy.", "protein": "CD30", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12349747" }, { "confidence": "high", "disease": "Classical Hodgkin lymphoma (cHL)", "glycan_involvement": "CD15 is a carbohydrate antigen (Lewis x); glycosylation is essential for its detection.", "mechanism": "CD15 is expressed on HRS cells and aids in immunophenotypic diagnosis.", "protein": "CD15", "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "high", "disease": "Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation modulates antibody binding.", "mechanism": "CD20 is expressed on NLPHL cells, distinguishing them from cHL.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect its serum stability.", "mechanism": "Hyperferritinemia is a diagnostic marker for HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "low", "disease": "Classical Hodgkin lymphoma (cHL)", "glycan_involvement": "LDH is glycosylated; glycosylation may affect secretion.", "mechanism": "LDH is monitored as a marker of tissue turnover and disease activity.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "medium", "disease": "Classical Hodgkin lymphoma (cHL)", "glycan_involvement": "ALP is glycosylated; glycosylation affects enzymatic activity.", "mechanism": "Elevated ALP may indicate hepatic involvement in HL.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "high", "disease": "Classical Hodgkin lymphoma (cHL)", "glycan_involvement": "Antibody glycosylation affects pharmacokinetics and immune effector function.", "mechanism": "Brentuximab vedotin targets CD30 on HRS cells for cytotoxic delivery.", "protein": "Brentuximab vedotin (anti-CD30)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349747" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation of CD30 may modulate immune signaling.", "mechanism": "HL (CD30+ cells) can trigger secondary HLH via cytokine release.", "protein": "CD30", "relationship_type": "causal", "source_pmcid": "PMC12349747" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "CD15 glycan structure is critical for immune recognition.", "mechanism": "CD15+ HL cells may drive HLH via immune dysregulation.", "protein": "CD15", "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "low", "disease": "Anemia of chronic disease", "glycan_involvement": "Glycosylation affects CD20 antibody targeting.", "mechanism": "CD20+ B cells may be involved in immune-mediated cytopenias.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349747" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Sialoglycan structures on GPA mediate virus binding.", "mechanism": "GPA acts as a receptor for SARS-CoV-2 via sialic acid-containing glycans, facilitating viral capture by RBCs and transfer to macrophages.", "protein": "Glycophorin A (GPA)", "protein_enriched": { "function": "Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Glycophorin A is the major intrinsic membrane protein of t", "gene_name": "GYPA", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G16370GQ", "G33350UC", "G42797SX", "G47180UC", "G56245IE", "G56682BC", "G65562ZE", "G94217FB", "G94435QH", "G29931IJ", "G49108TO", "G81006GJ", "G57321FI", "G29068FM", "G43417UB", "G02030ZB", "G09480OP", "G14127XU", "G19399OS", "G31916IQ", "G32948PW", "G33947BV", "G74722FL", "G76163CP", "G85608AG", "G91473PK" ], "uniprot_id": "P02724" }, "relationship_type": "causal", "source_pmcid": "PMC12349834" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation status affects GPA-mediated RBC-virus interactions.", "mechanism": "Altered GPA function or expression may contribute to RBC dysfunction and anemia in COVID-19 patients.", "protein": "Glycophorin A (GPA)", "protein_enriched": { "function": "Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Glycophorin A is the major intrinsic membrane protein of t", "gene_name": "GYPA", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G16370GQ", "G33350UC", "G42797SX", "G47180UC", "G56245IE", "G56682BC", "G65562ZE", "G94217FB", "G94435QH", "G29931IJ", "G49108TO", "G81006GJ", "G57321FI", "G29068FM", "G43417UB", "G02030ZB", "G09480OP", "G14127XU", "G19399OS", "G31916IQ", "G32948PW", "G33947BV", "G74722FL", "G76163CP", "G85608AG", "G91473PK" ], "uniprot_id": "P02724" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "medium", "disease": "Bleeding/Coagulopathy", "glycan_involvement": "Glycosylation modulates platelet glycoprotein function and clearance.", "mechanism": "COVID-19 and diabetes cause reduced platelet count and altered platelet volume, increasing bleeding risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "medium", "disease": "Bleeding/Coagulopathy", "glycan_involvement": "N-glycosylation affects prothrombin activation and stability.", "mechanism": "Prolonged prothrombin time in COVID-19/diabetes patients indicates acquired coagulopathy.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation impacts RBC lifespan and aggregation.", "mechanism": "COVID-19 and diabetes lead to reduced RBC count and altered membrane glycoprotein function, contributing to anemia.", "protein": "Red blood cell membrane glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Hyperglycemia can modify glycan structures on GPA.", "mechanism": "Diabetes may alter GPA glycosylation, affecting RBC function and susceptibility to infection.", "protein": "Glycophorin A (GPA)", "protein_enriched": { "function": "Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Glycophorin A is the major intrinsic membrane protein of t", "gene_name": "GYPA", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G16370GQ", "G33350UC", "G42797SX", "G47180UC", "G56245IE", "G56682BC", "G65562ZE", "G94217FB", "G94435QH", "G29931IJ", "G49108TO", "G81006GJ", "G57321FI", "G29068FM", "G43417UB", "G02030ZB", "G09480OP", "G14127XU", "G19399OS", "G31916IQ", "G32948PW", "G33947BV", "G74722FL", "G76163CP", "G85608AG", "G91473PK" ], "uniprot_id": "P02724" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation changes modulate platelet reactivity.", "mechanism": "Diabetes alters platelet glycoprotein glycosylation, affecting platelet function and coagulation.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Altered N-glycosylation may affect prothrombin activity.", "mechanism": "Diabetes may affect prothrombin glycosylation, impacting coagulation.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status influences RBC-virus interactions.", "mechanism": "COVID-19 alters RBC membrane glycoprotein function, contributing to anemia and immune response.", "protein": "Red blood cell membrane glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "low", "disease": "Bleeding/Coagulopathy", "glycan_involvement": "Glycosylation modulates GPA-mediated cell interactions.", "mechanism": "Altered GPA may affect RBC-platelet interactions and bleeding risk in COVID-19/diabetes.", "protein": "Glycophorin A (GPA)", "protein_enriched": { "function": "Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Glycophorin A is the major intrinsic membrane protein of t", "gene_name": "GYPA", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G16370GQ", "G33350UC", "G42797SX", "G47180UC", "G56245IE", "G56682BC", "G65562ZE", "G94217FB", "G94435QH", "G29931IJ", "G49108TO", "G81006GJ", "G57321FI", "G29068FM", "G43417UB", "G02030ZB", "G09480OP", "G14127XU", "G19399OS", "G31916IQ", "G32948PW", "G33947BV", "G74722FL", "G76163CP", "G85608AG", "G91473PK" ], "uniprot_id": "P02724" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349834" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob disease (CJD)", "glycan_involvement": "Glycosylation affects PrP folding, trafficking, and aggregation propensity.", "mechanism": "Misfolding of PrP from normal (PrPC, alpha-helix) to pathogenic (PrPSc, beta-sheet) form induces neurodegeneration.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC12349964" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob disease (CJD)", "glycan_involvement": "Glycosylation may influence protein stability and detection in CSF.", "mechanism": "Elevated CSF levels indicate rapid neuronal damage and are used in CJD diagnosis.", "protein": "14-3-3 gamma protein", "protein_enriched": { "function": "Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of part", "gene_name": "YWHAG", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70316RW", "G49108TO" ], "uniprot_id": "P61981" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349964" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob disease (CJD)", "glycan_involvement": "Tau glycosylation can modulate aggregation and neurotoxicity.", "mechanism": "High CSF T-tau reflects acute neuronal injury and is diagnostic for CJD.", "protein": "T-tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC12349964" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not directly discussed; AST is a glycoprotein, but glycosylation not implicated in mechanism.", "mechanism": "Elevated AST reflects tissue injury during acute SARS-CoV-2 infection, mainly nonhepatic origin.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12350042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not directly discussed; ALT is a glycoprotein, but glycosylation not implicated in mechanism.", "mechanism": "ALT elevation may indicate hepatic injury in severe SARS-CoV-2 infection.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12350042" }, { "confidence": "high", "disease": "Transaminase elevation", "glycan_involvement": "Not discussed.", "mechanism": "AST elevation is primarily due to nonhepatic tissue injury in pediatric COVID-19 cases.", "protein": "AST", "relationship_type": "causal", "source_pmcid": "PMC12350042" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Not discussed.", "mechanism": "ALT elevation is associated with hepatic injury, especially in severe COVID-19.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12350042" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated, which modulates immune evasion and tissue targeting.", "mechanism": "Spike protein mediates viral entry and tissue tropism, including potential liver tropism.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12350042" }, { "confidence": "low", "disease": "Liver failure", "glycan_involvement": "Not discussed.", "mechanism": "Elevated AST may signal risk for liver failure in severe pediatric COVID-19, though not observed in this cohort.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12350042" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Spike glycosylation affects cell entry and immune response.", "mechanism": "Direct viral injury to liver cells is plausible via spike-mediated entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12350042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not discussed.", "mechanism": "Lower AST levels observed in vaccinated children, suggesting protection from severe tissue injury.", "protein": "AST", "relationship_type": "protective", "source_pmcid": "PMC12350042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not discussed.", "mechanism": "Vaccination associated with lower ALT elevation, indicating reduced hepatic injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12350042" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein is critical for vaccine design and immune recognition.", "mechanism": "Spike protein is the target of COVID-19 vaccines, conferring protection against severe disease and organ injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350042" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation modulates aggregation propensity and toxicity.", "mechanism": "Aggregation of misfolded \u03b1-synuclein forms Lewy bodies, driving neurodegeneration.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC12351063" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation affects enzyme stability and activity.", "mechanism": "COMT degrades levodopa; inhibition prolongs dopamine action.", "protein": "COMT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351063" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation modulates enzyme localization and activity.", "mechanism": "MAO-B degrades dopamine; inhibition reduces oxidative stress and prolongs dopamine signaling.", "protein": "MAO-B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation required for secretion and neurotrophic function.", "mechanism": "BDNF promotes neuronal survival and is upregulated by curcumin.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation influences stability and calcium-binding capacity.", "mechanism": "Calbindin buffers intracellular calcium, protecting dopaminergic neurons.", "protein": "Calbindin", "protein_enriched": { "function": "Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase", "gene_name": "Calb1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50282JC" ], "uniprot_id": "P12658" }, "relationship_type": "protective", "source_pmcid": "PMC12351063" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation essential for membrane localization and function.", "mechanism": "DAT levels reflect dopaminergic neuron integrity; reduced in PD.", "protein": "Dopamine transporter (DAT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, Pu", "gene_name": "SLC6A3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q01959" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "N-glycosylation affects enzyme activity and stability.", "mechanism": "SOD neutralizes ROS; upregulated by polyphenols in PD models.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "O-glycosylation modulates nuclear translocation and transcriptional activity.", "mechanism": "NF-\u03baB drives pro-inflammatory cytokine expression; inhibited by celastrol.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "N-glycosylation required for enzymatic activity.", "mechanism": "HO-1 is upregulated by resveratrol/quercetin, conferring antioxidant protection.", "protein": "Heme oxygenase-1 (HO-1)", "relationship_type": "protective", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Elevated TGF-\u03b21 reflects neuroinflammatory state in PD; reduced by Mucuna pruriens and levodopa.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351063" }, { "confidence": "medium", "disease": "Broncho-biliary fistula (BBF)", "glycan_involvement": "O-glycosylation affects mucin viscosity and barrier function.", "mechanism": "Mucin glycoproteins in bronchial secretions may interact with bile, contributing to inflammation and fistula formation.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12351173" }, { "confidence": "medium", "disease": "Broncho-biliary fistula (BBF)", "glycan_involvement": "N-glycosylation modulates enzyme stability and activity.", "mechanism": "Bile glycoproteins leak into bronchial tree, causing necrosis and fistula formation.", "protein": "Bile salt-stimulated lipase", "relationship_type": "causal", "source_pmcid": "PMC12351173" }, { "confidence": "high", "disease": "Hydatid cyst", "glycan_involvement": "N-glycosylation influences antibody effector function.", "mechanism": "IgG response to hydatid cyst wall glycoproteins is used for serological diagnosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12351173" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Alpha-1-antitrypsin limits protease-mediated lung damage during infection.", "protein": "Alpha-1-antitrypsin", "relationship_type": "protective", "source_pmcid": "PMC12351173" }, { "confidence": "low", "disease": "Cholestasis", "glycan_involvement": "Minor glycosylation, limited impact.", "mechanism": "Serum albumin levels decrease in hepatic dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351173" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation affects enzyme activity.", "mechanism": "Elevated glycoprotein levels indicate biliary obstruction.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351173" }, { "confidence": "medium", "disease": "Hepatic cytolysis", "glycan_involvement": "N-glycosylation site occupancy changes in liver disease.", "mechanism": "Altered glycoforms reflect hepatic injury.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351173" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation modulates immune function.", "mechanism": "Acute phase glycoprotein elevated in infection.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351173" }, { "confidence": "low", "disease": "Angiocholitis", "glycan_involvement": "Glycosylation affects solubility and immune recognition.", "mechanism": "Bile glycoproteins contribute to inflammation in biliary tract.", "protein": "Bile acids conjugated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351173" }, { "confidence": "high", "disease": "Hydatid cyst", "glycan_involvement": "Glycosylation patterns modulate antigenicity.", "mechanism": "Glycoproteins in cyst wall elicit host immune response and facilitate cyst survival.", "protein": "Hydatid cyst wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351173" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Panel includes glycoprotein enzymes (ALT, AST) whose glycosylation may affect serum levels.", "mechanism": "FIB-4 is used to predict significant liver fibrosis in MASLD patients.", "protein": "FIB-4 (Fibrosis-4 Index)", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect enzyme stability and serum detection.", "mechanism": "ALT elevation reflects hepatocellular injury and predicts disease progression.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may modulate enzyme activity and clearance.", "mechanism": "AST elevation is associated with liver inflammation and fibrosis progression.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis affects albumin half-life and function.", "mechanism": "Low serum albumin indicates advanced liver dysfunction in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation affects platelet lifespan and clearance.", "mechanism": "Low platelet count is a surrogate marker for portal hypertension in cirrhosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may influence serum levels and diagnostic accuracy.", "mechanism": "ALT is used to monitor disease activity and response to therapy in MASH.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may influence serum levels and diagnostic accuracy.", "mechanism": "AST is used to monitor disease progression and fibrosis in MASH.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Depends on glycoprotein components (ALT, AST, platelets).", "mechanism": "FIB-4 is used to stratify risk of advanced fibrosis and cirrhosis.", "protein": "FIB-4 (Fibrosis-4 Index)", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "Autoimmune liver disease (AILD)", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "ALT is used to monitor disease activity and treatment response.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "medium", "disease": "Viral hepatitis", "glycan_involvement": "Glycosylation may affect enzyme clearance.", "mechanism": "AST is used to assess liver inflammation and progression in viral hepatitis.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12351529" }, { "confidence": "high", "disease": "Blindness", "glycan_involvement": "Rhodopsin is a glycoprotein; glycosylation is essential for its stability and function in photoreceptor cells.", "mechanism": "Vitamin A deficiency impairs rhodopsin synthesis, leading to night blindness and vision loss.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "medium", "disease": "Hypovitaminosis A", "glycan_involvement": "Altered glycosylation may affect rhodopsin folding and trafficking.", "mechanism": "Defective rhodopsin synthesis is a hallmark of vitamin A deficiency.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351754" }, { "confidence": "medium", "disease": "Optic nerve atrophy", "glycan_involvement": "Glycoproteins are critical for axonal maintenance; altered glycosylation may exacerbate degeneration.", "mechanism": "Vitamin A deficiency leads to bone remodeling defects, compressing the optic nerve and causing degeneration.", "protein": "Optic nerve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "medium", "disease": "Retinal abnormalities", "glycan_involvement": "Proper glycosylation is required for epithelial cell function and photoreceptor support.", "mechanism": "Vitamin A deficiency disrupts epithelial differentiation, affecting retinal structure.", "protein": "Retinal pigment epithelium glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "medium", "disease": "Retinal abnormalities", "glycan_involvement": "Glycosylation defects may worsen rhodopsin instability.", "mechanism": "Impaired rhodopsin leads to rod cell degeneration and retinal pigment disruption.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "low", "disease": "Papilledema", "glycan_involvement": "Glycoproteins in the optic nerve head may be involved in edema response.", "mechanism": "Increased CSF pressure from vitamin A deficiency causes optic disc swelling.", "protein": "Optic nerve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "low", "disease": "Blindness", "glycan_involvement": "Glycosylation is essential for epithelial barrier and trophic functions.", "mechanism": "Disrupted epithelial support leads to photoreceptor dysfunction and vision loss.", "protein": "Retinal pigment epithelium glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351754" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "gE is a glycoprotein; its glycosylation is essential for immunogenicity and antigenicity in the vaccine.", "mechanism": "RZV vaccine uses recombinant gE to elicit protective humoral and cell-mediated immunity against VZV reactivation.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation of gE affects antibody recognition and immune response measurement.", "mechanism": "Anti-gE antibody titres serve as a biomarker for vaccine-induced immunity in immunosuppressed RA patients.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "biomarker", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylated gE is required for optimal antigen presentation and T-cell activation.", "mechanism": "Vaccination with recombinant gE reduces incidence of HZ in RA patients on immunosuppressive therapy.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "protective", "source_pmcid": "PMC12352179" }, { "confidence": "medium", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation modulates gE function in viral entry and immune evasion.", "mechanism": "gE is a key envelope protein required for VZV infectivity and cell-to-cell spread, contributing to HZ pathogenesis.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "causal", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation influences T-cell epitope presentation.", "mechanism": "gE-specific CD4+ T-cell frequency is a biomarker for cell-mediated immunity post-vaccination.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "biomarker", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation is necessary for proper folding and immunogenicity.", "mechanism": "gE is the antigenic target in RZV, driving both humoral and cellular immune responses.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation enhances antigenicity and antibody binding.", "mechanism": "Anti-gE antibodies confer protection against VZV reactivation in immunosuppressed RA patients.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "protective", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation status affects antibody response measurement.", "mechanism": "Magnitude of anti-gE antibody response correlates with vaccine efficacy.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "biomarker", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation modulates T-cell epitope accessibility.", "mechanism": "gE-specific T-cell responses are critical for long-term protection against HZ.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "protective", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Herpes Zoster", "glycan_involvement": "Glycosylation is essential for vaccine antigen structure and immune recognition.", "mechanism": "RZV-induced immunity against gE reduces HZ incidence in RA patients on JAK inhibitors.", "protein": "Glycoprotein E (gE) of Varicella-Zoster Virus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12352179" }, { "confidence": "high", "disease": "Retinitis pigmentosa 59 (RP59)", "glycan_involvement": "Defective dolichol-mediated N-glycosylation pathway in retina.", "mechanism": "Missense variants (K42E, T206A, R98W) impair dolichol synthesis, affecting glycosylation and leading to selective retinal degeneration.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "high", "disease": "Congenital disorders of glycosylation (CDG)", "glycan_involvement": "Essential for N-glycosylation in all tissues.", "mechanism": "Severe DHDDS loss-of-function disrupts global protein glycosylation, causing systemic CDG.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Epileptic encephalopathies", "glycan_involvement": "Defective N-glycosylation in neurons.", "mechanism": "Certain DHDDS variants cause neurological disease via impaired glycosylation in the brain.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Myoclonus ataxia", "glycan_involvement": "N-glycosylation defects in CNS.", "mechanism": "DHDDS mutations impair glycosylation, affecting neuronal function.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Intellectual deficit disorder (IDD)", "glycan_involvement": "N-glycosylation defects in CNS.", "mechanism": "DHDDS variants disrupt glycosylation, leading to neurodevelopmental deficits.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Parkinson-like symptoms", "glycan_involvement": "N-glycosylation defects in CNS.", "mechanism": "DHDDS mutations impair glycosylation, contributing to neurodegeneration.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Retinitis pigmentosa 59 (RP59)", "glycan_involvement": "Alters N-glycan processing in retina.", "mechanism": "ALG6 F304S polymorphism modifies severity of RP59, affecting cone and rod disease.", "protein": "ALG6", "protein_enriched": { "function": "Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)", "gene_name": "ALG6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9Y672" }, "relationship_type": "modifier", "source_pmcid": "PMC12352288" }, { "confidence": "high", "disease": "Congenital disorders of glycosylation (CDG)", "glycan_involvement": "Required for N-glycosylation.", "mechanism": "NUS1 is essential for dolichol synthesis; mutations cause CDG.", "protein": "NUS1 (NgBR)", "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "high", "disease": "Retinitis pigmentosa 59 (RP59)", "glycan_involvement": "Likely due to altered dolichol chain length affecting glycosylation of retinal proteins.", "mechanism": "DHDDS K42E and T206A variants cause inner retinal thinning, bipolar/amacrine cell loss, and impaired synaptic transmission.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "high", "disease": "Retinitis pigmentosa 59 (RP59)", "glycan_involvement": "Altered dolichol species impact N-glycosylation efficiency.", "mechanism": "DHDDS mutations cause shortened dolichol species, shifting glycan carrier profile in retina.", "protein": "DHDDS", "protein_enriched": { "function": "With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery (PubMed:25066056, PubMed:28842490, PubMed:3", "gene_name": "DHDDS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86SQ9" }, "relationship_type": "causal", "source_pmcid": "PMC12352288" }, { "confidence": "medium", "disease": "Arteriovenous fistula thrombosis", "glycan_involvement": "Semaglutide is a glycopeptide; glycosylation may affect its pharmacokinetics.", "mechanism": "Semaglutide dose escalation temporally associated with extensive AV fistula thrombosis, possibly via dehydration-induced hemoconcentration.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12352808" }, { "confidence": "medium", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Semaglutide glycosylation may influence receptor binding and half-life.", "mechanism": "Meta-analysis suggests increased DVT risk; mechanism may involve dehydration and increased blood viscosity.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12352808" }, { "confidence": "low", "disease": "Portal vein thrombosis", "glycan_involvement": "Glycosylation relevant to drug stability.", "mechanism": "Case report links semaglutide use to portal vein thrombosis.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12352808" }, { "confidence": "low", "disease": "Superior mesenteric vein thrombosis", "glycan_involvement": "Glycosylation impacts drug action.", "mechanism": "Dose escalation associated with thrombosis in case report.", "protein": "Dulaglutide", "relationship_type": "causal", "source_pmcid": "PMC12352808" }, { "confidence": "low", "disease": "Deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation affects pharmacodynamics.", "mechanism": "DVT reported after tirzepatide initiation.", "protein": "Tirzepatide", "relationship_type": "causal", "source_pmcid": "PMC12352808" }, { "confidence": "medium", "disease": "Thrombotic disease", "glycan_involvement": "GLP-1 receptor is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "GLP-1 receptor activation may reduce platelet aggregation via eNOS and nitric oxide.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "protective", "source_pmcid": "PMC12352808" }, { "confidence": "low", "disease": "Thrombotic disease", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "Exenatide impairs platelet aggregation in vitro.", "protein": "Exenatide", "relationship_type": "protective", "source_pmcid": "PMC12352808" }, { "confidence": "medium", "disease": "Thrombotic disease", "glycan_involvement": "eNOS is glycosylated; glycosylation affects enzyme localization.", "mechanism": "GLP-1 agonists activate eNOS, increasing nitric oxide and reducing platelet activation.", "protein": "Endothelial nitric oxide synthase (eNOS)", "relationship_type": "protective", "source_pmcid": "PMC12352808" }, { "confidence": "medium", "disease": "Thrombotic disease", "glycan_involvement": "Glycosylation critical for platelet glycoprotein function.", "mechanism": "Platelet glycoproteins mediate aggregation; GLP-1 agonists may modulate their function.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12352808" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation enhances drug stability and receptor affinity.", "mechanism": "Semaglutide improves glycemic control and reduces cardiovascular risk.", "protein": "Semaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12352808" }, { "confidence": "high", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Increased sialylation and altered galactosylation/fucosylation on IgG N-glycans drive pathogenicity.", "mechanism": "Aberrantly glycosylated IgG induces podocyte injury via cytoskeletal disruption, altered calcium handling, and metabolic reprogramming.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12353585" }, { "confidence": "high", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Specific glycan chains (e.g., G20 up, G18 down) serve as biomarkers.", "mechanism": "Distinct IgG glycosylation patterns (e.g., increased triantennary sialylated glycans) distinguish LN from nonrenal SLE and remission.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Normalization of sialylation/galactosylation after immunosuppression.", "mechanism": "Reversal of aberrant IgG glycosylation with treatment correlates with LN remission.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12353585" }, { "confidence": "high", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Indirect; mediated by IgG glycan-driven signaling.", "mechanism": "Aberrantly glycosylated IgG represses nephrin expression, contributing to podocyte injury and proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Upregulated in response to glycosylated LN-IgG exposure.", "mechanism": "Elevated PKM expression in podocytes and urine correlates with LN activity.", "protein": "Pyruvate kinase M (PKM)", "relationship_type": "biomarker", "source_pmcid": "PMC12353585" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered sialylation, galactosylation, and fucosylation.", "mechanism": "IgG glycosylation patterns differentiate SLE with and without renal involvement.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Sustained pathogenic glycan patterns.", "mechanism": "Persistent aberrant IgG glycosylation in LN leads to podocyte loss and progression to chronic kidney disease.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Increased galactosylation after treatment is associated with remission.", "mechanism": "Terminal galactosylation on IgG N-glycans is protective against podocyte injury.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Fucosylated IgG is more pathogenic.", "mechanism": "Core fucosylation on IgG N-glycans promotes podocyte injury.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12353585" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Indirect; effect mediated by IgG glycan-driven injury.", "mechanism": "Podocin expression is reduced in podocytes exposed to aberrantly glycosylated IgG, contributing to podocyte dysfunction.", "protein": "Podocin", "protein_enriched": { "function": "Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton", "gene_name": "NPHS2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP85" }, "relationship_type": "causal", "source_pmcid": "PMC12353585" }, { "confidence": "high", "disease": "Viral infections (e.g., influenza)", "glycan_involvement": "Sialylated and O-acetylated N-glycans at the tailpiece site (N340-IgA1/N327-IgA2)", "mechanism": "Sialylated N-glycans at the tailpiece interfere with sialic-acid-binding viruses, mediating antiviral activity.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12353717" }, { "confidence": "medium", "disease": "Inflammatory bowel diseases", "glycan_involvement": "Site-specific N-glycan modifications (sulfation, O-acetylation)", "mechanism": "Micro-heterogeneity of IgA N-glycosylation (including rare sulfated and O-acetylated N-glycans) may serve as biomarkers.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12353717" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Sulfated and O-acetylated N-glycans at specific sites", "mechanism": "Altered IgA glycosylation profiles (including rare N-glycans) are associated with disease state.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12353717" }, { "confidence": "medium", "disease": "Autoimmune diseases (general)", "glycan_involvement": "Site-specific N-glycan micro-heterogeneity (e.g., sialylation, sulfation)", "mechanism": "IgA's anti-inflammatory activity is modulated by its N-glycosylation profile; potential for therapeutic engineering.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12353717" }, { "confidence": "low", "disease": "Tumors/cancer", "glycan_involvement": "Tailpiece and CH2 domain N-glycans", "mechanism": "IgA effector functions (e.g., tumor cell killing) are influenced by N-glycosylation, suggesting potential for glycoengineering.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12353717" }, { "confidence": "medium", "disease": "Viral infections (e.g., influenza)", "glycan_involvement": "Sulfated HexNAc on N-glycans at tailpiece and CH2 domain", "mechanism": "Sulfated N-glycan epitopes can act as ligands for viral proteins, influencing infection or immune response.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC12353717" }, { "confidence": "medium", "disease": "Autoimmune diseases (general)", "glycan_involvement": "Subclass- and site-specific N-glycosylation (e.g., sialylation, sulfation)", "mechanism": "IgA inhibits inflammatory and autoimmune diseases, with glycosylation modulating this effect.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12353717" }, { "confidence": "high", "disease": "Acid sphingomyelinase deficiency (ASMD)", "glycan_involvement": "ASM is a glycoprotein; glycosylation affects its lysosomal targeting and stability.", "mechanism": "Mutations in SMPD1 gene cause deficiency of ASM, leading to sphingomyelin accumulation in tissues.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Niemann-Pick disease type A/B", "glycan_involvement": "Glycosylation is required for proper ASM function.", "mechanism": "Deficiency of ASM results in neurovisceral and visceral manifestations characteristic of NPD type A/B.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Acid sphingomyelinase deficiency (ASMD)", "glycan_involvement": "Therapeutic ASM is glycosylated for lysosomal delivery and activity.", "mechanism": "Olipudase alfa replaces deficient ASM, reducing sphingomyelin accumulation and improving clinical outcomes.", "protein": "Olipudase alfa (recombinant human ASM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "ASM glycosylation affects its activity in lysosomes.", "mechanism": "ASM deficiency leads to sphingomyelin accumulation in spleen and bone marrow, causing platelet sequestration and impaired production.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation required for ASM function.", "mechanism": "Sphingomyelin accumulation disrupts bone marrow function, leading to anemia.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Hepatosplenomegaly", "glycan_involvement": "ASM glycosylation affects lysosomal targeting.", "mechanism": "Sphingomyelin buildup in liver and spleen causes organ enlargement.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation impacts ASM stability and function.", "mechanism": "ASM deficiency alters lipid metabolism, leading to elevated cholesterol and triglycerides.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation of olipudase alfa is required for lysosomal uptake.", "mechanism": "ERT with olipudase alfa improves platelet counts by reducing sphingomyelin in spleen and bone marrow.", "protein": "Olipudase alfa (recombinant human ASM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Hepatosplenomegaly", "glycan_involvement": "Glycosylation enables lysosomal targeting.", "mechanism": "ERT reduces liver and spleen size by clearing sphingomyelin.", "protein": "Olipudase alfa (recombinant human ASM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354355" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Altered glycosylation of membrane glycoproteins affects platelet function.", "mechanism": "Sphingomyelin and cholesterol accumulation alters glycoprotein composition, impairing platelet aggregation and adhesion.", "protein": "Platelet membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12354355" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Glycosylation affects adiponectin multimerization and bioactivity.", "mechanism": "Serum adiponectin levels inversely correlate with diabetes risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates adiponectin stability and function.", "mechanism": "Low adiponectin is associated with increased cardiovascular risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation influences resistin secretion and activity.", "mechanism": "Elevated resistin is linked to insulin resistance and diabetes.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Menopause-related disorders", "glycan_involvement": "N-glycosylation is essential for FSH secretion and receptor binding.", "mechanism": "FSH levels rise post-menopause, reflecting endocrine changes.", "protein": "FSH (CGA|FSHB)", "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Menopause-related disorders", "glycan_involvement": "N-glycosylation required for LH bioactivity.", "mechanism": "LH increases after menopause, indicating gonadal aging.", "protein": "LH (CGA|LHB)", "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Menopause-related disorders", "glycan_involvement": "Complex N-glycosylation modulates hCG stability and function.", "mechanism": "Elevated hCG heterodimers in women reflect post-menopausal hormonal changes.", "protein": "hCG (CGA|CGB3|CGB7)", "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation patterns in PSA are linked to cancer progression.", "mechanism": "PSA is a clinical marker for prostate cancer.", "protein": "PSA/KLK3", "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects MMP3 secretion and activity.", "mechanism": "Higher MMP3 in men may relate to vascular remodeling and disease risk.", "protein": "MMP3", "protein_enriched": { "function": "Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activa", "gene_name": "MMP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P08254" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "medium", "disease": "Late-onset Alzheimer's disease", "glycan_involvement": "Glycosylation may influence NTM cell adhesion properties.", "mechanism": "NTM gene SNPs associated with Alzheimer's risk; serum NTM increases with age.", "protein": "NTM", "protein_enriched": { "function": "Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization a", "gene_name": "IBTK", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59324HL", "G80920RR", "G49108TO" ], "uniprot_id": "Q9P2D0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates VSIG4 immune function.", "mechanism": "VSIG4 is linked to insulin resistance and kidney EMT under hyperglycemia.", "protein": "VSIG4", "relationship_type": "biomarker", "source_pmcid": "PMC12354868" }, { "confidence": "high", "disease": "Limb-Girdle Muscular Dystrophy Type R2 (LGMDR2)", "glycan_involvement": "Dysferlin is a glycoprotein; glycosylation may affect its membrane localization and function.", "mechanism": "Loss-of-function mutations in dysferlin cause muscle fiber degeneration and progressive weakness.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "high", "disease": "Limb-Girdle Muscular Dystrophy Type R2 (LGMDR2)", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation can affect HDL function.", "mechanism": "Low circulating HDL-C is prevalent in LGMDR2 patients and may contribute to muscle degeneration.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Limb-Girdle Muscular Dystrophy Type R2 (LGMDR2)", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB-100); glycosylation affects LDL receptor binding.", "mechanism": "Elevated non-HDL cholesterol (including LDL) is common in LGMDR2 and may exacerbate muscle pathology.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may modulate dysferlin's role in vesicle trafficking and lipid metabolism.", "mechanism": "Dysferlin deficiency disrupts muscle cholesterol homeostasis, leading to systemic dyslipidemia.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Niemann\u2013Pick Disease", "glycan_involvement": "Glycosylation is essential for lysosomal targeting and function.", "mechanism": "Deficiency leads to lysosomal cholesterol accumulation; discussed as a parallel to dysferlinopathy.", "protein": "Acid Sphingomyelinase", "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "ABCA1 is glycosylated; glycosylation affects its stability and cholesterol efflux function.", "mechanism": "Mutations in ABCA1 cause low HDL-C; referenced as a genetic cause of dyslipidemia.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "ANGPTL4 glycosylation modulates its secretion and activity.", "mechanism": "Mutations in ANGPTL4 affect HDL metabolism; referenced as a genetic cause of low HDL-C.", "protein": "ANGPTL4", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697", "gene_name": "ANGPTL4", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G14994KB", "G22310AV", "G23863VK", "G27058EU", "G31852PQ", "G37412TK", "G37881RL", "G41071NU", "G45395BF", "G45495MK", "G48414YA", "G52527GH", "G56784JY", "G57818FI", "G62461SM", "G62765YT", "G71146HJ", "G75983OB", "G80920RR", "G84452RH", "G90659AW", "G43417UB", "G53434XO", "G88713AC" ], "uniprot_id": "Q9BY76" }, "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LCAT glycosylation is required for enzymatic activity.", "mechanism": "LCAT mutations cause low HDL-C; referenced as a genetic cause of dyslipidemia.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "causal", "source_pmcid": "PMC12355193" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Not directly discussed.", "mechanism": "Dysferlin deficiency does not increase atherosclerosis risk despite dyslipidemia.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12355193" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "HDL glycoprotein glycosylation affects anti-atherogenic properties.", "mechanism": "Low HDL-C is a risk factor for atherosclerosis; observed in LGMDR2 but not linked to increased atherosclerosis in patients.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12355193" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "O-glycosylation with fucose/mannose enables CLR recognition.", "mechanism": "Interacts with DC-SIGN on dendritic cells, modulates immune response, supports gut health and protects against colitis.", "protein": "SlpA", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "O-glycosylation required for immune receptor binding.", "mechanism": "Mincle recognition of glycosylated SLP triggers innate immune signaling, modulating inflammation.", "protein": "SLP-8321", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "medium", "disease": "Listeria infection", "glycan_involvement": "O-mannosylation critical for CLR interaction.", "mechanism": "Interacts with SIGNR1, regulates dendritic cell function and intestinal immunity, enhances resistance to infection and colitis.", "protein": "LspA", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "O-glycosylation required for export and function.", "mechanism": "Promotes gut homeostasis, inhibits apoptosis, protects epithelial barrier, prevents tight junction disruption.", "protein": "Msp1/p75", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "high", "disease": "Infectious disease", "glycan_involvement": "O-glycosylation with GlcNAc/sialic acid essential for binding.", "mechanism": "Glycosylation enables adhesion to host keratin/fibrinogen, promoting colonization and virulence.", "protein": "Srr1", "relationship_type": "causal", "source_pmcid": "PMC12355684" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Zwitterionic structure and TLR2 signaling required.", "mechanism": "Induces IL-10+ Tregs, suppresses Th17 inflammation, maintains immune tolerance.", "protein": "PSA (Polysaccharide A)", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Zwitterionic glycan structure mediates immune modulation.", "mechanism": "Expands CD39+ Tregs via TLR2, suppresses neuroinflammation.", "protein": "PSA (Polysaccharide A)", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "medium", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Glycan structure required for TLR2/4 pathway activation.", "mechanism": "Induces IL-10, inhibits ZP4, prevents inflammation.", "protein": "PSA (Polysaccharide A)", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Sphingolipid glycan structure modulates iNKT cell response.", "mechanism": "Suppresses colonic iNKT cell activation, prevents excessive inflammation.", "protein": "GSL-Bf717", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "medium", "disease": "Candida albicans infection", "glycan_involvement": "O-glycosylation required for export and antifungal activity.", "mechanism": "Inhibits hyphal formation and biofilm, prevents fungal adhesion.", "protein": "Msp1/p75", "relationship_type": "protective", "source_pmcid": "PMC12355684" }, { "confidence": "high", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "LGALS3BP is a secreted glycoprotein; its glycosylation mediates interactions with immune cells and extracellular matrix.", "mechanism": "Elevated LGALS3BP expression correlates with increased immune cell infiltration, inflammation, and plaque instability in AS.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "Glycosylation affects LGALS3BP\u2019s binding to Galectin-3 and immune modulation.", "mechanism": "Modulation of LGALS3BP or its pathways may attenuate inflammatory and proliferative responses driving plaque progression.", "protein": "LGALS3BP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation status may influence LGALS3BP\u2019s role in fibrosis and inflammation.", "mechanism": "Elevated plasma LGALS3BP levels are associated with adverse cardiac remodeling and increased fibrosis.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation mediates immune cell recruitment and signaling.", "mechanism": "Upregulated LGALS3BP is linked to inflammation and tissue damage post-infarction.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "Cancer (Breast, Colon, Lung)", "glycan_involvement": "Glycosylation modulates cell adhesion, migration, and immune evasion.", "mechanism": "LGALS3BP is elevated in multiple solid tumors, associated with tumor aggressiveness and prognosis.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "HIV Infection", "glycan_involvement": "Glycosylation affects LGALS3BP\u2019s interaction with viral and host proteins.", "mechanism": "LGALS3BP regulates viral replication and host immune responses, influencing disease progression.", "protein": "LGALS3BP", "relationship_type": "causal", "source_pmcid": "PMC12355831" }, { "confidence": "high", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "Glycosylation is essential for LGALS3BP\u2019s extracellular functions.", "mechanism": "Promotes pro-inflammatory cytokine secretion, macrophage activation, and immune cell recruitment, driving plaque formation.", "protein": "LGALS3BP", "relationship_type": "causal", "source_pmcid": "PMC12355831" }, { "confidence": "high", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "Glycosylation mediates immune cell interactions.", "mechanism": "High LGALS3BP expression correlates with activated dendritic cells, NK cells, CD4/CD8 T cells, and Tregs in AS lesions.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "medium", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "Glycosylation may influence cell-type specific interactions.", "mechanism": "Negative correlation with resting mast cells, M0 macrophages, and eosinophils may indicate a regulatory role in immune balance.", "protein": "LGALS3BP", "relationship_type": "protective", "source_pmcid": "PMC12355831" }, { "confidence": "high", "disease": "Coronary Atherosclerosis (AS)", "glycan_involvement": "Glycosylation status may affect biomarker reliability.", "mechanism": "Plasma LGALS3BP levels predict severity and adverse cardiovascular events in AS.", "protein": "LGALS3BP", "relationship_type": "biomarker", "source_pmcid": "PMC12355831" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-glycosylation of dystrophin is important for membrane interactions; loss may affect protein stability.", "mechanism": "Loss-of-function mutations in DMD gene lead to absence of Dp427m, causing muscle membrane instability and degeneration.", "protein": "Dystrophin (Dp427m)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "O-glycosylation may be altered in truncated forms, affecting protein function.", "mechanism": "In-frame mutations produce truncated but partially functional Dp427m, resulting in milder muscle disease.", "protein": "Dystrophin (Dp427m)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Cognitive impairment (ID, autism, ADHD)", "glycan_involvement": "O-glycosylation may influence Dp140 stability and neuronal localization.", "mechanism": "Mutations affecting Dp140 isoform expression are associated with intellectual disability and neurodevelopmental disorders.", "protein": "Dystrophin (Dp140)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-7" }, "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Cognitive impairment (ID, autism, ADHD)", "glycan_involvement": "O-glycosylation may affect Dp71 function in neurons.", "mechanism": "Loss of Dp71 isoform in brain linked to cognitive and behavioral deficits.", "protein": "Dystrophin (Dp71)", "protein_enriched": { "function": "", "gene_name": "DMD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11532-8" }, "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation status may modulate neuronal membrane interactions.", "mechanism": "Deficiency of brain dystrophin isoforms may contribute to epilepsy in DMD patients.", "protein": "Dystrophin (Dp427m)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy", "glycan_involvement": "N-glycosylation is critical for laminin function and muscle basement membrane stability.", "mechanism": "Pathogenic variants in LAMA2 cause merosin-deficient congenital muscular dystrophy.", "protein": "Laminin subunit alpha-2 (Merosin, LAMA2)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Cardiomyopathy in DMD/BMD", "glycan_involvement": "O-glycosylation may affect dystrophin's interaction with cardiac muscle membrane.", "mechanism": "Dystrophin deficiency leads to cardiac muscle degeneration and heart failure.", "protein": "Dystrophin (Dp427m)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Loss of ambulation in DMD", "glycan_involvement": "Glycosylation may modulate dystrophin stability and localization.", "mechanism": "Absence of dystrophin correlates with early loss of ambulation.", "protein": "Dystrophin (Dp427m)", "relationship_type": "biomarker", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "Elevated creatine kinase (CK) in DMD/BMD", "glycan_involvement": "Indirect; glycosylation affects membrane integrity.", "mechanism": "Muscle membrane instability due to dystrophin loss causes CK leakage.", "protein": "Dystrophin (Dp427m)", "relationship_type": "biomarker", "source_pmcid": "PMC12355978" }, { "confidence": "medium", "disease": "Orthopedic complications (scoliosis, contractures)", "glycan_involvement": "Glycosylation may influence dystrophin's structural role.", "mechanism": "Muscle weakness and degeneration from dystrophin deficiency lead to skeletal deformities.", "protein": "Dystrophin (Dp427m)", "relationship_type": "causal", "source_pmcid": "PMC12355978" }, { "confidence": "high", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Glycosylation creates the 'glycan shield' and 'glycan hole' epitopes, influencing antibody binding and immune evasion.", "mechanism": "Env is targeted by neutralizing antibodies; specific epitopes (e.g., glycan hole, V2/V3 region) are recognized by monoclonal antibodies derived from immune sera.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Glycan holes are regions with missing glycans, exposing protein epitopes for antibody binding.", "mechanism": "Antibodies targeting the glycan hole and V2/V3 regions can neutralize HIV-1 and are associated with protection in vaccine studies.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "protective", "source_pmcid": "PMC12356236" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Glycosylation patterns modulate epitope exposure and immunogenicity.", "mechanism": "Epitope-specific antibody responses to Env can serve as biomarkers of vaccine-induced immunity.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "Influenza (H3N2)", "glycan_involvement": "Glycosylation affects NA structure and antibody accessibility to the active site.", "mechanism": "NA is targeted by inhibitory monoclonal antibodies that block its enzymatic activity, preventing viral release.", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "Influenza (H3N2)", "glycan_involvement": "Glycosylation may influence the conformation of the active site and antibody binding.", "mechanism": "Monoclonal antibodies binding the NA active site confer in vivo protection against lethal influenza challenge in mice.", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12356236" }, { "confidence": "medium", "disease": "Influenza (H3N2)", "glycan_involvement": "Glycosylation state can affect antigenicity and immune recognition.", "mechanism": "NA-specific antibody responses indicate effective vaccination and correlate with protection.", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Dense N-glycosylation shields key epitopes from neutralizing antibodies.", "mechanism": "Env mediates viral entry into host cells; its glycosylation is essential for infectivity and immune evasion.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "Influenza (H3N2)", "glycan_involvement": "N-glycosylation modulates enzymatic activity and immune recognition.", "mechanism": "NA is required for viral release from infected cells; its function is essential for viral propagation.", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12356236" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Specific N-glycans are required for antibody binding to certain broadly neutralizing epitopes.", "mechanism": "Monoclonal antibodies targeting glycan-dependent epitopes are being developed as therapeutics.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356236" }, { "confidence": "medium", "disease": "Influenza (H3N2)", "glycan_involvement": "Glycosylation may affect the efficacy of antibody binding and inhibition.", "mechanism": "NA-inhibiting antibodies can serve as therapeutic agents to prevent or treat influenza.", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356236" }, { "confidence": "high", "disease": "Poor growth performance in broilers", "glycan_involvement": "IGF-1 is a glycoprotein; glycosylation may affect its stability and bioactivity, though not directly studied here.", "mechanism": "IGF-1 promotes muscle growth and upregulates myogenic factors (Pax7, Myf5, MyoD), improving body weight and muscle fibre size.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356441" }, { "confidence": "high", "disease": "Marek\u2019s disease", "glycan_involvement": "gB is a glycoprotein; glycosylation is important for viral infectivity and immune recognition.", "mechanism": "HVT gB is a component of the HVT vaccine, conferring immunity against Marek\u2019s disease.", "protein": "Herpesvirus of turkey glycoprotein B (HVT gB)", "relationship_type": "protective", "source_pmcid": "PMC12356441" }, { "confidence": "medium", "disease": "Marek\u2019s disease", "glycan_involvement": "No direct involvement discussed.", "mechanism": "IGF-1 delivered by HVT vector does not interfere with HVT\u2019s protective effect against Marek\u2019s disease.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "neutral", "source_pmcid": "PMC12356441" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Altered glycosylation may modulate AGP's inflammatory activity.", "mechanism": "AGP levels are positively associated with hepatic fat accumulation, reflecting systemic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Potential threshold-dependent glycosylation changes affect AGP's role in fibrosis.", "mechanism": "AGP shows a nonlinear (L-shaped) association with liver stiffness; above a threshold, higher AGP correlates with increased fibrosis.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation patterns may influence AGP's biomarker utility.", "mechanism": "Elevated AGP is associated with NAFLD presence and severity.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Loss of sialylation/fucosylation in AGP correlates with cirrhosis.", "mechanism": "AGP levels and glycosylation (asialo form) are altered in cirrhosis, potentially reflecting disease progression.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered glycan structures serve as diagnostic markers.", "mechanism": "AGP glycosylation changes (sialylation/fucosylation) are observed in HCC patients.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "low", "disease": "Renal fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Elevated AGP is implicated in renal fibrosis as an inflammatory marker.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "low", "disease": "Kidney failure", "glycan_involvement": "Not specified.", "mechanism": "AGP is elevated in progressive kidney failure.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357468" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Threshold-dependent glycosylation may shift AGP from protective to pro-fibrotic.", "mechanism": "Above a threshold, AGP may promote fibrosis via inflammatory and fibrogenic pathways.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal (potential)", "source_pmcid": "PMC12357468" }, { "confidence": "low", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may modulate AGP's inflammatory signaling.", "mechanism": "AGP may contribute to steatosis progression through inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal (potential)", "source_pmcid": "PMC12357468" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "Reduced glycosylation in cirrhosis may decrease AGP's function.", "mechanism": "Low AGP may reflect impaired hepatic synthesis in advanced cirrhosis.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "protective (potential, low AGP)", "source_pmcid": "PMC12357468" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation is essential for LRG secretion and stability as an acute-phase glycoprotein.", "mechanism": "LRG is upregulated in inflamed gingival tissues, correlates with disease severity and clinical parameters (PI, GI, GBI, PPD, CAL); produced locally by inflammatory cells.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation required for LRG function and detection in serum.", "mechanism": "Serum LRG levels are elevated in active UC and correlate with disease activity.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation enables LRG's role as a serum biomarker.", "mechanism": "LRG evaluated as an inflammatory marker for disease activity.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation affects LRG's interaction with cell receptors and stability.", "mechanism": "LRG modulates TGF-\u03b2 signaling, promotes cellular proliferation, differentiation, and angiogenesis, contributing to periodontal tissue damage.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "causal", "source_pmcid": "PMC12357680" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation required for ELISA detection and biomarker utility.", "mechanism": "LRG levels decrease after non-surgical periodontal therapy, paralleling clinical improvement.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation is necessary for CRP's function and detection.", "mechanism": "CRP is elevated in response to inflammation and tissue damage in periodontitis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation influences SAA's stability and function.", "mechanism": "SAA levels rise significantly during acute-phase response in periodontal inflammation.", "protein": "Serum amyloid A protein (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation may affect tissue localization and biomarker performance.", "mechanism": "LRG expression is higher in deeper periodontal pockets, correlating with increased epithelial permeability and inflammation.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation required for LRG's secretion and immune interactions.", "mechanism": "LRG is induced by inflammatory mediators (IL-6, IL-22, LPS) that drive periodontitis progression.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "high", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation enables LRG's secretion and stability in tissue.", "mechanism": "Local production of LRG by macrophages and neutrophils in inflamed gingival tissue.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG, LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12357680" }, { "confidence": "high", "disease": "GLUT1 Deficiency Syndrome", "glycan_involvement": "GLUT1 is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "GLUT1 mutations impair glucose transport into the brain, causing seizures and developmental delay.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "high", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Direct involvement in N-glycosylation pathway.", "mechanism": "ALG13 mutations disrupt N-glycosylation, leading to congenital disorders of glycosylation and epilepsy.", "protein": "ALG13", "protein_enriched": { "function": "Catalytic subunit of the UDP-N-acetylglucosamine transferase complex that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine", "gene_name": "ALG13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP73" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "medium", "disease": "West Syndrome (WS)/Infantile Spasms (IS)", "glycan_involvement": "Potential glycosylation may affect protein stability/function (not detailed in article).", "mechanism": "CDKL5 mutations cause severe early-onset epilepsy and developmental delay.", "protein": "CDKL5", "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "medium", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Potential glycosylation may modulate synaptic function (not detailed in article).", "mechanism": "STXBP1 mutations impair synaptic vesicle release, leading to epilepsy.", "protein": "STXBP1", "protein_enriched": { "function": "Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins (By similarity). Essential for neurotransmission and binds syntaxin, a component of ", "gene_name": "STXBP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61764" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "high", "disease": "Dravet Syndrome (DS)", "glycan_involvement": "Glycosylation modulates channel trafficking and gating.", "mechanism": "SCN1A mutations disrupt sodium channel function, causing DS.", "protein": "SCN1A", "protein_enriched": { "function": "Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated s", "gene_name": "SCN1A", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35498" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "medium", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Glycosylation may affect channel surface expression.", "mechanism": "KCNQ2 mutations impair potassium channel function, leading to epilepsy.", "protein": "KCNQ2", "protein_enriched": { "function": "Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:24277843, PubMed:28793216, PubMed:9836639).", "gene_name": "KCNQ2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43526" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "medium", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Glycosylation modulates channel function.", "mechanism": "SCN2A mutations disrupt sodium channel function, causing epilepsy.", "protein": "SCN2A", "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "high", "disease": "West Syndrome (WS)/Infantile Spasms (IS)", "glycan_involvement": "ACTH is glycosylated, affecting its stability and receptor interaction.", "mechanism": "ACTH is used as first-line therapy to suppress seizures.", "protein": "ACTH (Adrenocorticotropic hormone)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12358386" }, { "confidence": "low", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Glycosylation may modulate channel function.", "mechanism": "HCN2 mutations affect neuronal excitability, leading to epilepsy.", "protein": "HCN2", "protein_enriched": { "function": "Hyperpolarization-activated ion channel that is permeable to sodium and potassium ions. Displays lower selectivity for K(+) over Na(+) ions (PubMed:10228147, PubMed:22006928). Contributes to the nativ", "gene_name": "HCN2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UL51" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "low", "disease": "Developmental Epileptic Encephalopathy (DEE)", "glycan_involvement": "Potential glycosylation (not detailed in article).", "mechanism": "ATN1 mutations associated with rare DEE subtypes.", "protein": "ATN1", "protein_enriched": { "function": "Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (PubMed:1", "gene_name": "RBBP8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99708" }, "relationship_type": "causal", "source_pmcid": "PMC12358386" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and function.", "mechanism": "CRP is elevated in chronic inflammation and used as a marker for systemic inflammatory status.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Physical quality of life reduction", "glycan_involvement": "Glycosylation of CRP is essential for its solubility and immune recognition.", "mechanism": "Higher circulating CRP is independently associated with lower physical quality of life.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "Composite N-acetyl glycan signals from multiple plasma glycoproteins.", "mechanism": "Glycoprotein acetyls are suggested as sensitive markers for metabolic disease and gut microbiome function.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "medium", "disease": "Quality of life reduction", "glycan_involvement": "IL-6 is glycosylated, which modulates its secretion and receptor binding.", "mechanism": "IL-6 is weakly but negatively associated with quality of life.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects CRP's interaction with immune cells.", "mechanism": "Elevated CRP is associated with increased risk of cardiovascular disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Metabolic disease", "glycan_involvement": "N-glycosylation modulates CRP's plasma half-life.", "mechanism": "CRP is elevated in metabolic syndrome and related conditions.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "medium", "disease": "Gut microbiome dysfunction", "glycan_involvement": "Reflects overall glycosylation changes in plasma proteins.", "mechanism": "Glycoprotein acetyls may reflect gut microbiome status and inflammation.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may affect CRP's role in neuroinflammation.", "mechanism": "Elevated CRP is associated with increased risk of depression.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation regulates IL-6 stability and activity.", "mechanism": "IL-6 is a key cytokine in chronic inflammatory states.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Arthritis", "glycan_involvement": "N-glycosylation is important for CRP's immune functions.", "mechanism": "CRP is elevated in inflammatory arthritis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361675" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP is elevated in response to systemic inflammation and infection.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates PCT secretion and half-life.", "mechanism": "PCT rises in bacterial infection and sepsis.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation influences BNP processing and clearance.", "mechanism": "BNP is elevated in cardiac and renal stress during severe illness.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Fc glycosylation modulates IgG effector functions.", "mechanism": "IgG mediates immune response against pathogens.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for C3 secretion and activity.", "mechanism": "C3 activation drives complement-mediated inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation essential for C4 function.", "mechanism": "C4 participates in classical complement pathway activation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "causal", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation affects albumin stability and transport.", "mechanism": "Low albumin reflects systemic inflammation and organ failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "N-glycosylation modulates ALP activity.", "mechanism": "ALP is elevated in hepatic dysfunction and cholestasis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "Glycosylation affects GGT localization and function.", "mechanism": "GGT is increased in liver injury and biliary obstruction.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362047" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation influences fibrinogen polymerization.", "mechanism": "Fibrinogen is essential for clot formation in thrombosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12362047" }, { "confidence": "high", "disease": "Prostate cancer (PCa)", "glycan_involvement": "PSMA is a glycoprotein; glycosylation is essential for its membrane localization and stability, affecting imaging efficacy.", "mechanism": "PSMA is highly expressed (~95%) on prostate cancer cells, enabling detection and staging via PSMA-targeted PET imaging.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Glycosylation may influence PSMA's cell surface expression and ligand binding in advanced disease.", "mechanism": "PSMA expression persists in mCRPC, allowing detection of metastatic lesions and enabling PSMA-targeted radioligand therapy.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12362063" }, { "confidence": "high", "disease": "Biochemical recurrence of prostate cancer (BCR)", "glycan_involvement": "Glycosylation supports PSMA's stability and detectability in recurrent disease.", "mechanism": "PSMA-PET detects recurrent disease at low PSA levels due to PSMA expression on residual/recurrent tumor cells.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "medium", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation may affect antibody or ligand binding to PSMA, influencing therapy efficacy.", "mechanism": "PSMA is targeted by radioligand therapies for selective delivery of cytotoxic agents to cancer cells.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362063" }, { "confidence": "medium", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation may contribute to heterogeneity in PSMA expression and imaging signal.", "mechanism": "PSMA expression heterogeneity impacts lesion detectability and characterization in imaging.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "medium", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation status may modulate PSMA's accessibility to imaging agents and therapeutics.", "mechanism": "PSMA expression is used for patient selection for PSMA-targeted therapies and for monitoring response.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "medium", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation ensures proper PSMA folding and surface expression, critical for imaging.", "mechanism": "PSMA-PET imaging is used for whole-body tumor burden assessment and staging.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "medium", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation affects PSMA's detectability by imaging agents.", "mechanism": "PSMA expression is leveraged for automated lesion detection and segmentation in AI-driven imaging analysis.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "low", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation patterns may differ between malignant and benign tissues, potentially affecting specificity.", "mechanism": "PSMA expression is used to distinguish malignant from benign lesions, though physiological expression in normal tissues can cause false positives.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "low", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Altered glycosylation may contribute to reduced PSMA expression or altered localization.", "mechanism": "Low or heterogeneous PSMA expression in some mCRPC lesions can lead to false negatives in imaging.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362063" }, { "confidence": "high", "disease": "Primary rectal cancer", "glycan_involvement": "CEA is a heavily N-glycosylated glycoprotein; its glycosylation is essential for stability, secretion, and immune recognition.", "mechanism": "CEA is overexpressed and secreted by proliferating rectal cancer cells, leading to elevated serum levels that correlate with tumor burden, invasion depth, and metastasis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "high", "disease": "Primary rectal cancer", "glycan_involvement": "N-glycosylation supports CEA secretion into serum.", "mechanism": "Serum CEA levels increase with tumor size, reflecting increased tumor cell mass and metabolic activity.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "high", "disease": "Primary rectal cancer", "glycan_involvement": "Glycosylation maintains CEA structure and function as a tumor marker.", "mechanism": "Serum CEA levels correlate with T stage (tumor invasion depth), indicating more aggressive disease.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "high", "disease": "Primary rectal cancer", "glycan_involvement": "N-glycans facilitate CEA's stability in circulation.", "mechanism": "Elevated CEA levels are associated with lymph node metastasis, reflecting systemic tumor dissemination.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "medium", "disease": "Primary rectal cancer", "glycan_involvement": "Glycosylation is required for CEA's secretion and detection.", "mechanism": "CEA levels are higher in cases with positive circumferential resection margin (CRM), indicating local invasiveness.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "medium", "disease": "Primary rectal cancer", "glycan_involvement": "N-glycosylation supports CEA's circulatory half-life.", "mechanism": "CEA is elevated in patients with extramural vascular invasion (EMVI), suggesting hematogenous spread.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "medium", "disease": "Primary rectal cancer", "glycan_involvement": "Glycosylation is necessary for CEA's stability and detection in serum.", "mechanism": "Postoperative decline in CEA indicates therapeutic efficacy; persistent elevation suggests recurrence or metastasis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "high", "disease": "Primary rectal cancer", "glycan_involvement": "N-glycans are essential for CEA's immunogenicity and detection by clinical assays.", "mechanism": "CEA is used for monitoring disease progression and recurrence.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362563" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "CEA is a heavily glycosylated protein; its glycan structures are critical for its stability and detection as a biomarker.", "mechanism": "CEA is overexpressed on tumor cell surfaces; elevated serum levels reflect tumor presence and progression.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Glycosylation affects CEA's cell adhesion properties, potentially influencing metastasis.", "mechanism": "High serum CEA correlates with metastatic disease.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Tumor recurrence", "glycan_involvement": "Glycan moieties are essential for CEA's immunogenicity and detection.", "mechanism": "Elevated CEA indicates recurrence after therapy.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Cytokeratin 19 is not a classical glycoprotein, but Cyfra21-1 detection may be influenced by glycosylation of associated proteins.", "mechanism": "Cyfra21-1 is released from tumor cells; elevated serum levels indicate NSCLC presence.", "protein": "Cytokeratin 19 fragment (Cyfra21-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Indirect; glycosylation of tumor cell surface proteins may facilitate Cyfra21-1 release.", "mechanism": "High Cyfra21-1 levels are associated with metastatic NSCLC.", "protein": "Cytokeratin 19 fragment (Cyfra21-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "VEGF is N-glycosylated, which is critical for its secretion and receptor binding.", "mechanism": "VEGF promotes angiogenesis; elevated levels correlate with tumor growth and progression.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "N-glycosylation modulates VEGF's bioactivity and stability.", "mechanism": "Increased VEGF levels are linked to lymphatic metastasis in NSCLC.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Tumor recurrence", "glycan_involvement": "Glycosylation affects VEGF's half-life and detection.", "mechanism": "Elevated VEGF after therapy may indicate recurrence.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12362653" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycan epitopes on CEA are recognized by therapeutic antibodies.", "mechanism": "CEA is a potential target for immunotherapy in NSCLC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362653" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation is required for VEGF's receptor interaction and function.", "mechanism": "VEGF inhibition (e.g., by anlotinib) reduces angiogenesis and tumor growth.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362653" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and A\u03b2 generation.", "mechanism": "Abnormal glycosylation and processing of APP leads to A\u03b2 deposition; polyphenols inhibit BACE1, reducing A\u03b2 production.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12363475" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates Tau aggregation.", "mechanism": "Hyperphosphorylation and abnormal O-glycosylation of Tau promote neurofibrillary tangle formation; polyphenols reduce Tau phosphorylation.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12363475" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation required for RAGE ligand binding.", "mechanism": "AGEs bind RAGE, activating inflammatory pathways and oxidative stress; polyphenols inhibit AGE-RAGE interaction.", "protein": "Receptor for Advanced Glycation End-products (RAGE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12363475" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of proteins (glycoproteins) forms AGEs.", "mechanism": "AGEs accumulate in hyperglycemia, drive complications via RAGE; polyphenols inhibit AGE formation.", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation critical for OPG secretion and function.", "mechanism": "OPG inhibits osteoclastogenesis; reduced OPG in osteoporosis; polyphenols may upregulate OPG.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Coronary heart disease", "glycan_involvement": "Glycosylation may affect S100A12 stability and secretion.", "mechanism": "S100A12 activates inflammatory signaling (NF-\u03baB), promoting atherosclerosis; polyphenols inhibit NF-\u03baB.", "protein": "S100A12", "protein_enriched": { "function": "Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does n", "gene_name": "S100A13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99584" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of HSA.", "mechanism": "HSA glycation (AGE-HSA) reflects glycemic control; polyphenols prevent HSA glycation.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for BACE1 stability and function.", "mechanism": "BACE1 cleaves APP to generate A\u03b2; polyphenols inhibit BACE1 expression/activity.", "protein": "BACE1 (Beta-secretase 1)", "protein_enriched": { "function": "Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generatio", "gene_name": "BACE1", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G80920RR", "G05724UK", "G06110VR", "G12398HZ", "G14023ZV", "G14669DU", "G15065YV", "G17689DH", "G21112KH", "G22310AV", "G22768VO", "G23863VK", "G25520XG", "G29880MM", "G39188ZX", "G44444MB", "G46687AB", "G49874UX", "G55220VL", "G60230HH", "G63889NK", "G64527OM", "G70101JE", "G70375MX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G80966KZ", "G84452RH", "G87618BG", "G90093AU", "G91636VS", "G93993PD", "G94854LT" ], "uniprot_id": "P56817" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Coronary heart disease", "glycan_involvement": "N-glycosylation affects IL-6 secretion.", "mechanism": "IL-6 promotes vascular inflammation; polyphenols reduce IL-6 production.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates TNF-\u03b1 secretion.", "mechanism": "TNF-\u03b1 drives chronic inflammation and tumorigenesis; polyphenols suppress TNF-\u03b1.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12363475" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation is required for secretion and receptor binding.", "mechanism": "VEGF regulates angiogenesis, which is essential for tumor growth and metastasis; serum VEGF is elevated in NSCLC.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "CA125 is a mucin-type glycoprotein; O-glycosylation is critical for its structure and detection.", "mechanism": "CA125 is elevated in NSCLC and aids in diagnosis, especially in combination with other markers.", "protein": "Cancer Antigen 125 (CA125)", "protein_enriched": { "function": "May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the", "gene_name": "DEDD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "CEA is heavily N-glycosylated (~60% carbohydrate); glycosylation affects its serum stability and immunogenicity.", "mechanism": "CEA is elevated in NSCLC and improves diagnostic accuracy when combined with other markers.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12364467" }, { "confidence": "medium", "disease": "Squamous Cell Carcinoma (NSCLC subtype)", "glycan_involvement": "Glycosylation supports VEGF secretion and function.", "mechanism": "Serum VEGF is significantly higher in squamous cell carcinoma compared to controls.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12364467" }, { "confidence": "medium", "disease": "Adenocarcinoma (NSCLC subtype)", "glycan_involvement": "O-glycosylation is essential for CA125's mucin properties.", "mechanism": "CA125 is elevated in adenocarcinoma subtype compared to controls.", "protein": "Cancer Antigen 125 (CA125)", "protein_enriched": { "function": "May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the", "gene_name": "DEDD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12364467" }, { "confidence": "medium", "disease": "Adenocarcinoma (NSCLC subtype)", "glycan_involvement": "N-glycosylation is important for CEA's function and detection.", "mechanism": "CEA is elevated in adenocarcinoma subtype compared to controls.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Glycosylation is necessary for VEGF's biological activity.", "mechanism": "Targeting VEGF-mediated angiogenesis is a therapeutic strategy in NSCLC.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "O-glycosylation enables CA125's detection in serum.", "mechanism": "CA125 is elevated even in early-stage NSCLC, supporting its use in early detection.", "protein": "Cancer Antigen 125 (CA125)", "protein_enriched": { "function": "May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the", "gene_name": "DEDD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF8" }, "relationship_type": "biomarker (early-stage)", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation is critical for CEA's stability and immunoreactivity.", "mechanism": "CEA is elevated in early-stage NSCLC, aiding early diagnosis.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker (early-stage)", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Glycosylation is required for VEGF's secretion and receptor interaction.", "mechanism": "VEGF-driven angiogenesis is necessary for NSCLC tumor growth and metastasis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12364467" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects its antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote thrombosis by disrupting endothelial function and activating coagulation.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycosylated phospholipid-binding proteins.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS and correlates with increased risk of thrombosis and stroke.", "protein": "Anticardiolipin antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Interacts with glycosylated plasma proteins involved in coagulation.", "mechanism": "Lupus anticoagulant positivity is associated with increased risk of arterial and venous thrombosis in APS.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "Recognizes glycosylated Ro antigens.", "mechanism": "Anti-SS-A/Ro antibodies are diagnostic for pSS and associated with increased risk of CNS involvement and stroke.", "protein": "Anti-SS-A/Ro antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Targets nuclear glycoproteins.", "mechanism": "ANA positivity is a hallmark of SLE and correlates with increased risk of stroke and other autoimmune manifestations.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Binds to glycosylated nuclear antigens.", "mechanism": "Anti-dsDNA antibodies are specific for SLE and associated with increased risk of vascular and CNS involvement.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Low C3 levels indicate complement activation and are associated with increased disease activity and risk of stroke in SLE.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "medium", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "C4 is a glycoprotein; glycosylation modulates complement activity.", "mechanism": "Low C4 levels are associated with increased risk of CNS involvement and stroke in pSS.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12364476" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of prothrombin affects its antigenicity and coagulation function.", "mechanism": "Autoantibodies against prothrombin contribute to thrombosis in APS.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "causal", "source_pmcid": "PMC12364476" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Annexin V is glycosylated; glycan structure may affect its protective function.", "mechanism": "Disruption of annexin V shield by aPL allows endothelial damage and thrombosis.", "protein": "Annexin V", "relationship_type": "causal", "source_pmcid": "PMC12364476" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Enhanced O-GlcNAcylation of key transcription factors and metabolic enzymes.", "mechanism": "Upregulation of GFPT1 increases HBP flux, promoting protein glycosylation and metabolic reprogramming, driving tumor growth and proliferation.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "O-GlcNAcylation of transcription factors and stemness markers.", "mechanism": "GFPT1 upregulation promotes tumor aggressiveness, lymph node metastasis, and stemness via increased HBP flux and glycosylation.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "O-GlcNAcylation and altered glycan synthesis affecting cell adhesion and migration.", "mechanism": "GFPT2 upregulation is associated with EMT, tumor invasion, migration, and metastasis; driven by KRAS and EMT transcription factors.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia", "glycan_involvement": "O-GlcNAcylation of signaling proteins modulates cell survival.", "mechanism": "GFPT1-driven O-GlcNAcylation inhibits apoptosis and promotes proliferation.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Serous ovarian cancer", "glycan_involvement": "O-GlcNAcylation and glycan remodeling facilitate metastatic phenotype.", "mechanism": "GFPT2 upregulation promotes EMT, cell invasion, and migration.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Increased O-GlcNAcylation impairs insulin signaling and protein function.", "mechanism": "GFPT1 activation in HBP pathway contributes to hyperglycemia-induced pathologies.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-GlcNAcylation and glycan changes drive aggressive phenotype.", "mechanism": "GFPT2 upregulation promotes tumor growth, EMT, and stemness, especially in claudin-low subtype.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-GlcNAcylation of stemness and migration-related proteins.", "mechanism": "High GFPT1 expression correlates with proliferation, migration, invasion, and poor prognosis.", "protein": "GFPT1", "relationship_type": "biomarker", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "O-GlcNAcylation of PTEN leads to its ubiquitination and loss of tumor suppressor function.", "mechanism": "GFPT1 increases HBP flux and PTEN O-GlcNAcylation, promoting PTEN degradation and PI3K/mTOR signaling.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Cholangiocarcinoma", "glycan_involvement": "O-GlcNAcylation and glycan remodeling support metastatic behavior.", "mechanism": "GFPT2 upregulation increases tumor invasion, migration, and EMT.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12365115" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Loss of O-mannosylated matriglycan chains on \u03b1-DG", "mechanism": "Hypoglycosylation of \u03b1-DG reduces matriglycan, impairing ECM binding and muscle integrity.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Defective O-glycosylation step in matriglycan synthesis", "mechanism": "FKRP mutations impair ribitol-5-phosphate addition, reducing matriglycan synthesis.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "LGMD2I/R9", "glycan_involvement": "Partial loss of matriglycan O-glycosylation", "mechanism": "L276I FKRP mutation leads to reduced matriglycan on \u03b1-DG, causing mild muscular dystrophy.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "Severe hypoglycosylation of matriglycan", "mechanism": "Severe FKRP mutations (e.g., P448L) cause near-complete loss of matriglycan, resulting in severe CMD.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "medium", "disease": "WWS", "glycan_involvement": "Defective O-mannosylation and matriglycan extension", "mechanism": "FKRP mutations disrupt matriglycan synthesis, leading to WWS phenotype.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "medium", "disease": "MEB", "glycan_involvement": "Impaired O-glycosylation of matriglycan", "mechanism": "FKRP mutations impair matriglycan, contributing to MEB disease.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "O-mannosylated glycan chain as disease biomarker", "mechanism": "Matriglycan levels correlate with disease severity and progression.", "protein": "matriglycan (on \u03b1-DG)", "relationship_type": "biomarker", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Loss of matriglycan O-glycosylation in heart tissue", "mechanism": "Reduced matriglycan in cardiac muscle leads to contractile dysfunction.", "protein": "matriglycan (on \u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Respiratory Failure", "glycan_involvement": "Reduced matriglycan O-glycosylation in diaphragm muscle", "mechanism": "Fibrosis and dysfunction in diaphragm due to matriglycan deficiency.", "protein": "matriglycan (on \u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Dystroglycanopathy", "glycan_involvement": "Enhanced O-glycosylation via increased CDP-ribitol substrate", "mechanism": "Ribitol supplementation restores matriglycan, improving muscle pathology and function.", "protein": "matriglycan (on \u03b1-DG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12367137" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Recognizes GalNAc/Tn antigen on tumor cells; glycosylation modulates immune evasion.", "mechanism": "ASGR1 suppresses tumor progression by inhibiting STAT3 phosphorylation and cell migration/invasion; loss of ASGR1 correlates with poor prognosis.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "biomarker/therapeutic_target/protective", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "Binds desialylated glycoproteins and HBV preS1 region; glycosylation critical for viral attachment.", "mechanism": "ASGR1 mediates HBV entry into hepatocytes via glycan recognition; targeted by GalNAc-conjugated antivirals.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "SARS-CoV-2 Infection (COVID-19)", "glycan_involvement": "Spike glycoprotein glycosylation enables ASGR1 binding.", "mechanism": "ASGR1 acts as alternative receptor for SARS-CoV-2 spike glycoprotein, mediating ACE2-independent viral entry.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Atherosclerosis (AS)", "glycan_involvement": "Regulates LDLR degradation via glycan recognition; impacts lipoprotein glycosylation.", "mechanism": "ASGR1 deficiency reduces LDL-C, improves lipid profile, and attenuates atherosclerotic lesions.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Recognizes exposed Gal/GalNAc on platelets after desialylation.", "mechanism": "ASGR1 clears desialylated platelets, stimulates hepatic TPO synthesis, and maintains platelet homeostasis.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12367805" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycan recognition modulates immune cell differentiation.", "mechanism": "ASGR1 promotes monocyte-to-macrophage differentiation, exacerbating inflammation and fibrosis.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Liver Injury", "glycan_involvement": "GP73 glycosylation enables ASGR1 recognition.", "mechanism": "ASGR1 mediates GP73 endocytosis and degradation; absence of ASGR1 leads to GP73 accumulation, ER stress, and worsened liver injury.", "protein": "Golgi Protein 73 (GP73)", "protein_enriched": { "function": "Unknown. Cellular response protein to viral infection", "gene_name": "GOLM1", "glycan_count": 61, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02030ZB", "G02628JF", "G02815KT", "G04657PL", "G08918WF", "G11911BT", "G14972EH", "G15664MX", "G26915XM", "G27126ED", "G31852PQ", "G33609NS", "G34989PA", "G37412TK", "G37881RL", "G39595FH", "G39619TI", "G40574BA", "G45395BF", "G48414YA", "G56284ZY", "G56784JY", "G57776ZS", "G57888GL", "G60834IK", "G62765YT", "G64409MC", "G64527OM", "G66163OV", "G66621EA", "G69108CV", "G70101JE", "G70223PD", "G70375MX", "G70822IO", "G72797UR", "G75607BQ", "G76295SF", "G79666IR", "G80920RR", "G81198YO", "G83229XP", "G83633GK", "G83951ZY", "G87123QX", "G90382BL", "G90734RJ", "G91473PK", "G92551JA", "G94470IW", "G95133RI", "G99966GV", "G57321FI", "G06356OH", "G11870QZ", "G12313PD", "G75983OB", "G82463GQ", "G49108TO", "G43417UB", "G29068FM" ], "uniprot_id": "Q8NBJ4" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycan-mediated LDLR degradation.", "mechanism": "ASGR1 deficiency increases LDLR and cholesterol efflux genes, reducing plasma lipid levels.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12367805" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "Recognition of N- or O-glycans on IgA1.", "mechanism": "ASGR1 clears circulating IgA, maintaining humoral immune homeostasis; altered clearance may contribute to cirrhosis pathology.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "Hepatitis E Virus Infection", "glycan_involvement": "Viral glycoprotein glycosylation enables ASGR1 binding.", "mechanism": "ASGR1 binds HEV ORF2 protein, facilitating hepatocyte entry and infection.", "protein": "Hepatitis E Virus ORF2 Protein", "relationship_type": "causal", "source_pmcid": "PMC12367805" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "STEAP3 is a glycoprotein; its membrane localization and potential glycosylation may influence receptor interactions.", "mechanism": "STEAP3 inhibits viral entry by interacting with ACE2, reducing SARS-CoV-2 infectivity in intestinal epithelium.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "protective", "source_pmcid": "PMC12368160" }, { "confidence": "high", "disease": "Enterovirus A71 (EV-A71) infection", "glycan_involvement": "STEAP3 and SCARB2 are glycoproteins; glycosylation may modulate their interaction.", "mechanism": "STEAP3 interacts with SCARB2, limiting EV-A71 binding and entry into host cells.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "protective", "source_pmcid": "PMC12368160" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation may affect STEAP3's interaction with ACE2 and viral entry.", "mechanism": "STEAP3 knockdown increases susceptibility to SARS-CoV-2, especially in enterocytes and enteroendocrine cells; restoring STEAP3 may reduce infection.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368160" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Membrane glycoprotein status may affect tissue localization and function.", "mechanism": "STEAP3 deficiency enhances viral dissemination through vascularized intestinal organoids, suggesting a role in limiting systemic spread.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "protective", "source_pmcid": "PMC12368160" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "Altered glycosylation in cancer may affect STEAP3 function.", "mechanism": "STEAP3 expression is lower in colon cancer organoids compared to cell lines; may relate to increased ACE2 and viral susceptibility.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12368160" }, { "confidence": "high", "disease": "Enterovirus A71 (EV-A71) infection", "glycan_involvement": "SCARB2 glycosylation is important for receptor function.", "mechanism": "SCARB2 acts as the cellular receptor for EV-A71, mediating viral entry.", "protein": "SCARB2", "protein_enriched": { "function": "Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting", "gene_name": "SCARB2", "glycan_count": 116, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G01521EA", "G05962QB", "G09831WQ", "G10773YW", "G11314AS", "G11870QZ", "G12313PD", "G16125XL", "G20210JR", "G23294PN", "G23984SE", "G25451PN", "G26377UA", "G30221QT", "G31309XD", "G32788FZ", "G35541EV", "G37818NZ", "G39471UU", "G42124LM", "G45395BF", "G47644PP", "G55132BD", "G60177UT", "G62894KT", "G65344XH", "G65414LI", "G67113SI", "G67164EE", "G68490OW", "G71051TA", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G82463GQ", "G82830MN", "G85269DF", "G87123QX", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94831VI", "G95046LV", "G95865ZB", "G09724ZC", "G11101UV", "G31852PQ", "G49755GI", "G52890YB", "G57489SP", "G69521XL", "G71463BG", "G76915KR", "G78811TO", "G98129XB", "G46071XJ", "G14260UH", "G15664MX", "G20425TQ", "G36442WJ", "G46503DX", "G46902YN", "G49018RC", "G49642SA", "G54010QB", "G56307ZW", "G60033FS", "G62765YT", "G64527OM", "G66621EA", "G70101JE", "G72747WU", "G83460ZZ", "G06583FZ", "G20312EM", "G44215PV", "G47012YE", "G77582RK", "G80223IX", "G81315DD", "G83229XP", "G22573RC", "G22768VO", "G37135JQ", "G46524LG", "G60230HH", "G83390WW", "G89864BN", "G00912UN", "G06247RL", "G08293MJ", "G10133VD", "G10846ZT", "G11629QQ", "G22310AV", "G27126ED", "G29526EI", "G31028YV", "G46691LC", "G47518TP", "G48414YA", "G58087IP", "G61751GZ", "G84452RH", "G85144OK", "G85554PZ", "G88374WZ", "G94470IW", "G96430BV", "G49108TO", "G06702MJ", "G06356OH", "G86795LJ", "G95133RI" ], "uniprot_id": "Q14108" }, "relationship_type": "causal", "source_pmcid": "PMC12368160" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "ACE2 glycosylation modulates spike protein binding and viral entry.", "mechanism": "ACE2 is the main entry receptor for SARS-CoV-2 in intestinal and other epithelial cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12368160" }, { "confidence": "medium", "disease": "Microcytic anemia", "glycan_involvement": "Not specified in this article.", "mechanism": "STEAP3 deficiency impairs iron metabolism, leading to microcytic anemia.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "causal", "source_pmcid": "PMC12368160" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation may influence STEAP3's interaction with variant spike proteins via ACE2.", "mechanism": "STEAP3 knockdown increases infection by multiple SARS-CoV-2 spike variants (D614G, B.1.1.7, V501Y.V2) in colon organoids.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "protective", "source_pmcid": "PMC12368160" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycoprotein status may affect vascular localization.", "mechanism": "STEAP3 deficiency increases viral infection in the vascular compartment of organoids, suggesting a role in preventing systemic viral spread.", "protein": "STEAP3", "protein_enriched": { "function": "Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the memb", "gene_name": "STEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFT2" }, "relationship_type": "protective", "source_pmcid": "PMC12368160" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Sialylation of CD24 is essential for Siglec-G/10 binding and anti-inflammatory signaling.", "mechanism": "CD24 interacts with Siglec-G/10 via sialic acid to suppress microglial NF-\u03baB activation and pro-inflammatory cytokine release.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "protective", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Recognition of sialylated glycans on CD24 is required for immune checkpoint function.", "mechanism": "Siglec-10/G binds sialylated CD24, recruiting SHP-1/2 phosphatases to inhibit NF-\u03baB pathway and reduce inflammation.", "protein": "Siglec-10/Siglec-G", "relationship_type": "protective", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Cardiac arrest-induced brain ischemia/reperfusion injury", "glycan_involvement": "Sialic acid residues on CD24 mediate neuroprotective signaling.", "mechanism": "Preservation of CD24 sialylation by neuraminidase inhibition (oseltamivir) protects against neuronal damage post-CA.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Removes sialic acid from CD24, abolishing its immune checkpoint function.", "mechanism": "Neuraminidase desialylates CD24, disrupting CD24-Siglec-G/10 interaction and amplifying microglial-driven inflammation.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12368432" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Sialylation of CD24 is required for Siglec-G/10-mediated immune suppression.", "mechanism": "CD24-Siglec-G/10 axis suppresses HMGB1-induced inflammation in sepsis; desialylation impairs this effect.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "protective", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Cardiac arrest-induced brain ischemia/reperfusion injury", "glycan_involvement": "Requires sialylated CD24 for checkpoint engagement.", "mechanism": "Enhancing Siglec-G/10 signaling (via CD24 sialylation) reduces NF-\u03baB activation and neuronal injury.", "protein": "Siglec-10/Siglec-G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Indirect; regulated by CD24-Siglec-G/10 complex formation.", "mechanism": "HMGB1 acts as a DAMP, activating TLR4/NF-\u03baB pathway and driving microglial inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12368432" }, { "confidence": "medium", "disease": "Post-cardiac arrest syndrome", "glycan_involvement": "Sialylation status affects biomarker reliability and function.", "mechanism": "Upregulation of CD24 correlates with neuroinflammatory status and response to therapy.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12368432" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Cleaves sialic acid from CD24, impairing Siglec-G/10 binding.", "mechanism": "Neuraminidase-mediated desialylation of CD24 disrupts immune checkpoint, leading to systemic inflammation.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12368432" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 is glycosylated, but glycan status not directly linked to mechanism here.", "mechanism": "Elevated IL-6 reflects microglial activation and inflammatory state post-ischemia.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12368432" }, { "confidence": "high", "disease": "Urinary Tract Infection (UTI)", "glycan_involvement": "High-mannose N-glycans mediate binding to bacterial adhesins (e.g., FimH of UPEC).", "mechanism": "UMOD binds to uropathogenic bacteria via its high-mannose N-glycans, preventing bacterial adhesion to urothelium.", "protein": "Uromodulin (UMOD)", "relationship_type": "protective", "source_pmcid": "PMC12368613" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation required for proper folding and function of E1 in fusion.", "mechanism": "E1 mediates viral membrane fusion with host cell; inhibition blocks viral entry.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "E2 mediates viral attachment to host cell receptors; inhibition blocks entry.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation stabilizes complex and modulates host interactions.", "mechanism": "Complex mediates viral entry; piperine binding inhibits fusion and attachment.", "protein": "E1-E2 glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368721" }, { "confidence": "medium", "disease": "Chronic Chikungunya disease", "glycan_involvement": "Glycosylation may affect chronicity via immune modulation.", "mechanism": "Persistent infection linked to E1-mediated fusion and viral persistence.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "causal", "source_pmcid": "PMC12368721" }, { "confidence": "medium", "disease": "Chronic Chikungunya disease", "glycan_involvement": "Glycosylation influences immune escape and tissue tropism.", "mechanism": "E2 enables ongoing cell attachment, contributing to chronic infection.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation sites may affect inhibitor binding and efficacy.", "mechanism": "Targeting E1-E2 with piperine reduces viral load and infection severity.", "protein": "E1-E2 glycoprotein complex", "relationship_type": "protective", "source_pmcid": "PMC12368721" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity.", "mechanism": "E2 presence used for immunofluorescence detection of infection.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "biomarker", "source_pmcid": "PMC12368721" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation status may influence mutation effects.", "mechanism": "E1 mutations linked to altered fusion and disease severity.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation may modulate pocket accessibility.", "mechanism": "Fusion pocket residues (e.g., MET88, LEU16) are key for inhibitor binding.", "protein": "E1-E2 glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation of E2 and host glycans mediates viral attachment.", "mechanism": "E2 interaction with host glycans (e.g., heparin) is essential for entry.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12368721" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "P-gp is a heavily N-glycosylated membrane glycoprotein; glycosylation is essential for its stability and trafficking.", "mechanism": "P-gp overexpression leads to efflux of chemotherapeutic drugs (e.g., doxorubicin), reducing efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Multidrug resistance (MDR)", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "ABCB1 gene encodes P-gp, which actively exports drugs out of cancer cells, causing MDR.", "protein": "ABCB1", "relationship_type": "causal", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation status may affect detection and function.", "mechanism": "Elevated P-gp expression correlates with poor response to chemotherapy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Inhibition may affect glycoprotein trafficking and function.", "mechanism": "Diosmetin inhibits P-gp activity and expression, enhancing doxorubicin efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation required for ABCB1 function.", "mechanism": "Downregulation of ABCB1 by diosmetin reduces drug efflux, increasing intracellular drug concentration.", "protein": "ABCB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12371033" }, { "confidence": "medium", "disease": "Multidrug resistance (MDR)", "glycan_involvement": "Glycosylation may modulate inhibitor binding.", "mechanism": "Flavonoids (e.g., diosmetin) inhibit P-gp, reversing MDR phenotype.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for functional upregulation.", "mechanism": "Doxorubicin treatment upregulates P-gp expression, promoting resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may influence binding pocket conformation.", "mechanism": "Molecular docking shows diosmetin binds P-gp, inhibiting its drug efflux function.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12371033" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation status may affect apoptosis signaling.", "mechanism": "Inhibition of P-gp by diosmetin increases apoptosis and DNA damage in cancer cells.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "protective", "source_pmcid": "PMC12371033" }, { "confidence": "low", "disease": "Chronic venous insufficiency", "glycan_involvement": "Glycosylation not directly discussed for this disease context.", "mechanism": "Diosmin (precursor of diosmetin) is used in chronic venous insufficiency; its metabolism may affect P-gp activity.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12371033" }, { "confidence": "high", "disease": "IgG4 Smoldering Multiple Myeloma (IgG4 SMM)", "glycan_involvement": "IgG4 glycosylation may affect antibody function and immune recognition.", "mechanism": "Monoclonal IgG4 production by malignant plasma cells; elevated serum IgG4 and IgG4+ plasma cell infiltration in bone marrow.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "high", "disease": "IgG4-related Autoimmune Hepatitis (IgG4-AIH)", "glycan_involvement": "Glycosylation of IgG4 modulates immune effector functions and tissue infiltration.", "mechanism": "IgG4+ plasma cell infiltration in liver tissue; elevated serum IgG4 associated with autoimmune hepatitis.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "high", "disease": "IgG4-related Disease (IgG4-RD)", "glycan_involvement": "Altered glycosylation may contribute to immune tolerance and chronic inflammation.", "mechanism": "Elevated serum IgG4 and tissue infiltration by IgG4+ plasma cells are diagnostic features.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation may affect antibody-antigen interactions in autoimmune response.", "mechanism": "Overlap syndrome with IgG4-AIH; IgG4+ plasma cell infiltration and anti-mitochondrial M2 antibody positivity.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "high", "disease": "IgG4 Smoldering Multiple Myeloma (IgG4 SMM)", "glycan_involvement": "Light chain glycosylation may influence aggregation and renal pathology.", "mechanism": "Monoclonal IgG4-Kappa detected in serum and bone marrow, indicating clonal plasma cell proliferation.", "protein": "Kappa light chain", "protein_enriched": { "function": "Constant region of immunoglobulin light chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGKC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01834" }, "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "medium", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "Glycosylation affects stability and clearance.", "mechanism": "Elevated serum beta-2-microglobulin reflects tumor burden and prognosis in MM.", "protein": "Beta-2-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation may affect antigenicity and immune response.", "mechanism": "Presence indicates autoimmune targeting of biliary epithelium.", "protein": "Anti-mitochondrial M2 antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "high", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "IgG glycosylation modulates effector functions and immune complex formation.", "mechanism": "Monoclonal IgG is the most common M protein in MM; subclass analysis (IgG1\u20134) is diagnostically relevant.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12371558" }, { "confidence": "medium", "disease": "IgG4-related Disease (IgG4-RD)", "glycan_involvement": "IgG4 glycosylation may reduce Fc receptor binding and effector function.", "mechanism": "IgG4+ plasma cell infiltration drives fibroinflammatory pathology in affected organs.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC12371558" }, { "confidence": "medium", "disease": "IgG4 Smoldering Multiple Myeloma (IgG4 SMM)", "glycan_involvement": "Glycosylation may influence antibody stability and immune escape.", "mechanism": "Clonal expansion of IgG4-producing plasma cells leads to SMM.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC12371558" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy autosomal recessive 21 (LGMDR21)", "glycan_involvement": "Loss of O-glucosylation on Notch EGF repeats", "mechanism": "Mutations in POGLUT1 reduce O-glucosylation of Notch receptors, impairing Notch signaling and satellite cell maintenance.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy autosomal recessive 21 (LGMDR21)", "glycan_involvement": "O-glucosylation of EGF repeats required for receptor activation", "mechanism": "Reduced POGLUT1 activity leads to hypoglycosylation of NOTCH1, decreasing its activation and downstream PAX7 expression.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy autosomal recessive 21 (LGMDR21)", "glycan_involvement": "O-glucosylation of EGF repeats", "mechanism": "POGLUT1-dependent O-glucosylation of NOTCH2 is necessary for its signaling in muscle progenitors.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy autosomal recessive 21 (LGMDR21)", "glycan_involvement": "O-glucosylation of EGF repeats", "mechanism": "POGLUT1 glycosylates NOTCH3 EGF repeats, promoting its activation; loss impairs muscle stem cell maintenance.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Satellite cell depletion", "glycan_involvement": "Indirect\u2014Notch glycosylation regulates PAX7 transcription", "mechanism": "PAX7 expression is reduced due to impaired Notch signaling from POGLUT1 deficiency.", "protein": "PAX7", "protein_enriched": { "function": "Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration", "gene_name": "PAX7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23759" }, "relationship_type": "biomarker", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Muscle growth defects", "glycan_involvement": "Loss of O-glucosylation on Notch receptors", "mechanism": "Conditional deletion of POGLUT1 in myogenic progenitors causes postnatal muscle growth retardation.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Impaired muscle repair", "glycan_involvement": "Loss of O-glucosylation on Notch receptors", "mechanism": "POGLUT1 deficiency in satellite cells impairs their activation and self-renewal after injury.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "medium", "disease": "Muscle growth defects", "glycan_involvement": "Reduced glycosylation (type not specified)", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan reduces laminin binding, contributing to extracellular matrix abnormalities.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Satellite cell depletion", "glycan_involvement": "Loss of O-glucosylation on Notch receptors", "mechanism": "Loss of POGLUT1 leads to premature differentiation and fusion of satellite cells, depleting the stem cell pool.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "causal", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Impaired muscle repair", "glycan_involvement": "Restoration of O-glucosylation on Notch receptors", "mechanism": "Restoration of POGLUT1 function rescues myogenic defects in patient-derived cells.", "protein": "POGLUT1", "protein_enriched": { "function": "", "gene_name": "CLRN3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NCR9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12373270" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Mediates O-glycosylation of cell surface proteins, affecting cell signaling and immune evasion.", "mechanism": "High GALNT2 expression predicts poor prognosis and promotes tumor progression.", "protein": "GALNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spect", "gene_name": "GALNT2", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q10471" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12374833" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Induces N-glycosylation of TGFBR2, affecting receptor stability and signaling.", "mechanism": "ALG3 upregulation confers therapy resistance and promotes tumor progression.", "protein": "ALG3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Component of OST complex, affecting N-glycosylation and protein folding.", "mechanism": "DAD1 regulates apoptosis and is associated with tumor progression.", "protein": "DAD1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Involved in glycan synthesis on glycoproteins, modulating cell-cell interactions.", "mechanism": "High expression correlates with poor prognosis.", "protein": "B4GALT1", "relationship_type": "biomarker", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Catalytic subunit of OST, mediates N-glycosylation of multiple proteins.", "mechanism": "Altered expression impacts tumor progression.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12374833" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "N-glycosylation generates ligands for EGFR, enhancing pathway activation.", "mechanism": "Aberrant glycosylation activates EGFR signaling, promoting tumor growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "N-glycosylation at receptor sites modulates HGF signaling.", "mechanism": "N-glycosylation of MET enhances EMT and therapy resistance.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation of AXL receptor tyrosine kinase.", "mechanism": "GALNT2 modifies O-glycosylation of AXL, promoting invasion.", "protein": "GALNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spect", "gene_name": "GALNT2", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q10471" }, "relationship_type": "causal", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation of TGFBR2.", "mechanism": "ALG3-mediated glycosylation of TGFBR2 confers therapy resistance.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12374833" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Affects N-glycosylation via OST complex.", "mechanism": "Altered DAD1 expression leads to protein misfolding and oncogenesis.", "protein": "DAD1", "relationship_type": "causal", "source_pmcid": "PMC12374833" }, { "confidence": "high", "disease": "MASLD/NASH", "glycan_involvement": "N-glycosylation affects IGFBP2 stability and secretion.", "mechanism": "Downregulation and hypermethylation of IGFBP2 in liver is associated with progression to NASH; IGFBP2 is protective against insulin resistance and hepatic fat accumulation.", "protein": "IGFBP2", "protein_enriched": { "function": "Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proli", "gene_name": "IGFBP2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "P18065" }, "relationship_type": "protective", "source_pmcid": "PMC12375920" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "N-glycosylation required for LPL activity and secretion.", "mechanism": "Epigenetic changes in LPL in visceral adipose tissue correlate with fasting glucose and HbA1c, linking lipid metabolism to T2D.", "protein": "LPL", "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Putative glycosylation may affect membrane localization.", "mechanism": "DNA methylation and expression changes in ATP11A in VAT are linked to diabetes traits.", "protein": "ATP11A", "protein_enriched": { "function": "Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and en", "gene_name": "ATP8A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2Q0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Putative glycosylation may regulate trafficking function.", "mechanism": "Epigenetic regulation of EHD2 in VAT correlates with diabetes traits; involved in membrane trafficking.", "protein": "EHD2", "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Putative glycosylation may affect transporter function.", "mechanism": "Blood DNA methylation at ABCG1 predicts future T2D; involved in insulin secretion and \u03b2-cell function.", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Putative glycosylation may affect protein stability.", "mechanism": "Epigenetic changes in ARHGAP26 in adipose tissue affect mitochondrial clearance and metabolic flexibility.", "protein": "ARHGAP26", "relationship_type": "causal", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Putative glycosylation may affect nuclear localization.", "mechanism": "Epigenetic regulation of ANP32B impacts chromatin organization and metabolic states in adipose tissue.", "protein": "ANP32B", "protein_enriched": { "function": "Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription (PubMed:18039846, PubMed:20015864). Regula", "gene_name": "ANP32B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q92688" }, "relationship_type": "causal", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "N-glycosylation affects collagen structure and ECM remodeling.", "mechanism": "meQTLs at COL11A2 locus in VAT associate with altered plasma fasting glucose.", "protein": "COL11A2", "protein_enriched": { "function": "Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involv", "gene_name": "GLTP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZD2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Putative glycosylation may affect enzyme activity.", "mechanism": "Correlated DNA methylation in blood and liver at ALOX12 links to insulin resistance.", "protein": "ALOX12", "protein_enriched": { "function": "Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corres", "gene_name": "ALOX12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P18054" }, "relationship_type": "biomarker", "source_pmcid": "PMC12375920" }, { "confidence": "high", "disease": "Obesity/Insulin Resistance", "glycan_involvement": "O-glycosylation (O-GlcNAc) at histone sites modulates transcription.", "mechanism": "O-GlcNAcylation of histones regulates chromatin structure and gene expression in response to nutrient status; altered in obesity and insulin resistance.", "protein": "O-GlcNAc-modified histones", "relationship_type": "causal", "source_pmcid": "PMC12375920" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "RET is a glycoprotein; glycosylation affects its cell surface localization and function.", "mechanism": "RET gene fusions drive NSCLC growth; inhibition by selpercatinib blocks oncogenic signaling.", "protein": "RET (Rearranged during Transfection)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378005" }, { "confidence": "medium", "disease": "Central nervous system metastases", "glycan_involvement": "Glycosylation may influence RET receptor trafficking and metastatic potential.", "mechanism": "RET fusion-positive NSCLC is associated with increased risk of CNS metastases.", "protein": "RET (Rearranged during Transfection)", "relationship_type": "causal", "source_pmcid": "PMC12378005" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation is essential for P-glycoprotein stability and drug transport function.", "mechanism": "P-glycoprotein modulates drug transport; selpercatinib is a substrate and inhibitor, affecting drug efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378005" }, { "confidence": "high", "disease": "Laminin \u03b12-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Laminin-\u03b12 is a glycoprotein; glycosylation is essential for its stability and extracellular matrix interactions.", "mechanism": "Mutations in LAMA2 gene lead to defective laminin-\u03b12, compromising muscle fiber integrity and causing progressive muscle weakness.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", 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"glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378348" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy-like phenotype", "glycan_involvement": "Altered glycosylation may affect residual protein function and phenotype severity.", "mechanism": "Partial loss-of-function mutations in LAMA2 can result in milder, later-onset muscle weakness resembling LGMD.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "causal", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Laminin \u03b12-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Detection relies on antibody recognition of glycosylated epitopes.", "mechanism": "Reduced or absent laminin-\u03b12 expression in muscle biopsy is diagnostic for LAMA2-RD.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378348" }, { "confidence": "medium", "disease": "Merosin-deficient congenital muscular dystrophy (MDC1A)", "glycan_involvement": "Therapies may aim to enhance glycosylation or protein stability.", "mechanism": "Restoring or stabilizing laminin-\u03b12 function is a potential therapeutic strategy.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Laminin \u03b12-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Frameshift mutations may disrupt glycosylation sites, affecting protein folding and secretion.", "mechanism": "Compound heterozygous mutations (missense and frameshift) in LAMA2 gene cause partial merosin deficiency and disease.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "causal", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy (MDC1A)", "glycan_involvement": "Loss of glycosylated protein disrupts extracellular matrix structure.", "mechanism": "Null mutations (e.g., frameshift deletions) in LAMA2 abolish laminin-\u03b12 production, leading to severe disease.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "causal", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Laminin \u03b12-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Glycosylation is required for proper protein-protein interactions in the complex.", "mechanism": "Disruption of laminin-\u03b12 impairs dystrophin-glycoprotein complex anchoring, causing muscle fiber degeneration.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "causal", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy (MDC1A)", "glycan_involvement": "Antibody-based detection depends on glycosylated epitopes.", "mechanism": "Immunohistochemical detection of merosin deficiency in muscle biopsy supports diagnosis.", "protein": "Laminin-211 (merosin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378348" }, { "confidence": "medium", "disease": "Laminin \u03b12-related muscular dystrophy (LAMA2-RD)", "glycan_involvement": "Restored protein must be properly glycosylated for full activity.", "mechanism": "Gene therapy and protein replacement strategies aim to restore laminin-\u03b12 function.", "protein": "Laminin-\u03b12 (LAMA2)", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMA2", "glycan_count": 114, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G06356OH", "G22310AV", "G27126ED", "G34989PA", "G37881RL", "G41071NU", "G43669FQ", "G45395BF", "G48414YA", "G90659AW", "G13694XX", "G25418HZ", "G27058EU", "G52527GH", "G56784JY", "G62765YT", "G80920RR", "G00912UN", "G02528FI", "G02815KT", "G02886BB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G27947YN", "G29545VG", "G35541EV", "G36379GD", "G37399XV", "G40574BA", "G43223CG", "G46691LC", "G60033FS", "G60834IK", "G63041LO", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G79666IR", "G80075MS", "G80479JV", "G81124ET", "G81263BG", "G84349RE", "G86880BF", "G87123QX", "G87661QW", "G92135MA", "G92275SC", "G93718GY", "G99668VU", "G01485JJ", "G59626AS", "G61256FT", "G92551JA", "G43089EG", "G70232NH", "G84452RH", "G04657PL", "G38663NM", "G86500WE", "G01650EU", "G10486CT", "G20210JR", "G23294PN", "G25451PN", "G42124LM", "G44215PV", "G48584BU", "G50045TK", "G64409MC", "G65184UU", "G72398FA", "G72790NZ", "G80223IX", "G83646BJ", "G20312EM", "G47748JZ", "G57888GL", "G31433PN", "G12793SR", "G15169WU", "G39595FH", "G47518TP", "G59536GA", "G93656SY", "G14972EH", "G33791AF", "G86795LJ", "G89205CJ", "G90382BL", "G43417UB", "G05609XV", "G28541PG", "G95865ZB", "G40834TG", "G60177UT", "G82830MN", "G57776ZS", "G07755XJ", "G31852PQ", "G40926MX", "G41247ZX", "G46503DX", "G64527OM", "G70101JE", "G86182NS", "G95177YH", "G49108TO" ], "uniprot_id": "P24043" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378348" }, { "confidence": "high", "disease": "Antiphospholipid antibody syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for APS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Evans syndrome", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Pre-existing anti-beta-2 glycoprotein I antibodies may predispose to Evans syndrome after viral trigger.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12379560" }, { "confidence": "high", "disease": "Antiphospholipid antibody syndrome (APS)", "glycan_involvement": "Glycosylation may affect epitope exposure.", "mechanism": "Anti-cardiolipin antibodies are diagnostic for APS.", "protein": "Cardiolipin-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Antiphospholipid antibody syndrome (APS)", "glycan_involvement": "Viral glycoprotein mimics host glycoproteins, inducing autoimmunity.", "mechanism": "VP1u region has phospholipase A2-like activity, triggers anti-phospholipid antibodies.", "protein": "Parvovirus B19 VP1 structural protein", "relationship_type": "causal", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Evans syndrome", "glycan_involvement": "Glycosylation of viral protein enhances mimicry.", "mechanism": "Molecular mimicry between VP1u and host antigens induces cross-reactive antibodies causing cytopenias.", "protein": "Parvovirus B19 VP1 structural protein", "relationship_type": "causal", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Potential glycan mimicry with host antigens.", "mechanism": "Anti-NS1 antibodies associated with increased risk of cytopenia and lupus.", "protein": "Parvovirus B19 NS1 protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12379560" }, { "confidence": "high", "disease": "Autoimmune hemolytic anemia (AIHA)", "glycan_involvement": "P antigen is a glycosphingolipid; glycan structure is essential for viral binding.", "mechanism": "Parvovirus B19 binds P antigen on erythroid progenitors, causing erythroid hypoplasia and anemia.", "protein": "Globoside (P antigen)", "relationship_type": "causal", "source_pmcid": "PMC12379560" }, { "confidence": "high", "disease": "Evans syndrome", "glycan_involvement": "IgG glycosylation modulates effector function and autoimmunity.", "mechanism": "IVIG used as therapy; autoantibodies (IgG) mediate cytopenias.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation of VP1u may enhance immune cross-reactivity.", "mechanism": "Cross-reactive antibodies against VP1u induce platelet destruction.", "protein": "Parvovirus B19 VP1 structural protein", "relationship_type": "causal", "source_pmcid": "PMC12379560" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "Autoantibodies against beta-2 glycoprotein I may contribute to thrombocytopenia.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12379560" }, { "confidence": "high", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Multiantennary branching and sialylation of N-glycans", "mechanism": "Increased multiantennary N-glycosylation enhances FVIII stability and half-life, raising circulating levels and VTE risk.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "causal", "source_pmcid": "PMC12379778" }, { "confidence": "high", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Multiantennary branching, sialylation, fucosylation", "mechanism": "Multiantennary and sialylated N-glycans prolong VWF half-life, increasing procoagulant activity and VTE risk.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC12379778" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Fucosylation and sialylation (sialyl Lewis X epitope)", "mechanism": "Fucosylated and sialylated N-glycans (sialyl Lewis X) on AGP promote selectin-mediated cell adhesion, inflammation, and thrombin generation.", "protein": "Alpha-1-acid glycoprotein (AGP/ORM1)", "relationship_type": "causal", "source_pmcid": "PMC12379778" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Oligomannose-type N-glycans", "mechanism": "Oligomannose-type N-glycans on apoB-100 are associated with reduced VTE risk, possibly via rapid clearance and inhibition of coagulation.", "protein": "Apolipoprotein B-100 (apoB-100)", "relationship_type": "protective", "source_pmcid": "PMC12379778" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Complex-type N-glycans, fucosylation", "mechanism": "Plasma N-glycan features correlate with FII activity, linking glycosylation to procoagulant potential.", "protein": "Coagulation Factor II (FII, prothrombin)", "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Complex-type N-glycans", "mechanism": "N-glycan traits associated with FXI activity and VTE risk.", "protein": "Coagulation Factor XI (FXI)", "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Complex-type N-glycans", "mechanism": "N-glycan features correlate with FIX antigen levels and VTE risk.", "protein": "Coagulation Factor IX (FIX)", "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "low", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "N-glycosylation", "mechanism": "Altered N-glycosylation of transferrin is a hallmark of CDG and may be relevant to VTE risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "low", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "N-glycosylation", "mechanism": "N-glycosylation changes in haptoglobin are diagnostic for CDG and may overlap with VTE glycan signatures.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "low", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "N-glycosylation (complex-type, fucosylation, sialylation)", "mechanism": "Global plasma N-glycan changes may reflect immunoglobulin glycosylation, influencing inflammation and VTE risk.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12379778" }, { "confidence": "high", "disease": "Nephrotic syndrome", "glycan_involvement": "Albumin glycosylation may affect stability and renal filtration.", "mechanism": "Low serum albumin reflects glomerular protein loss and disease severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "high", "disease": "Nephrotic syndrome", "glycan_involvement": "IgG glycosylation modulates immune function and clearance.", "mechanism": "Urinary loss of IgG leads to hypogammaglobulinemia and increased infection risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "medium", "disease": "Steroid-resistant nephrotic syndrome (SRNS)", "glycan_involvement": "Glycosylation may affect FKBP12 stability and drug binding.", "mechanism": "Tacrolimus acts via FKBP12 to suppress immune response; rifampicin reduces tacrolimus levels via CYP3A4/P-glycoprotein induction.", "protein": "Tacrolimus-binding protein (FKBP12)", "protein_enriched": { "function": "Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents th", "gene_name": "FKBP1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62942" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380572" }, { "confidence": "high", "disease": "Drug-induced hormone resistance", "glycan_involvement": "Glycosylation affects CYP3A4 localization and activity.", "mechanism": "Rifampicin induces CYP3A4, accelerating metabolism of prednisone and tacrolimus, causing resistance.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12380572" }, { "confidence": "high", "disease": "Drug-induced hormone resistance", "glycan_involvement": "N-glycosylation critical for P-glycoprotein trafficking and function.", "mechanism": "Rifampicin induces P-glycoprotein, reducing tacrolimus absorption and efficacy.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12380572" }, { "confidence": "medium", "disease": "Tuberculous pleurisy", "glycan_involvement": "O-glycosylation of mucins modulates viscosity and immune interactions.", "mechanism": "Elevated mucin in pleural fluid indicates inflammation and infection.", "protein": "Serous mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "medium", "disease": "Tuberculous pleurisy", "glycan_involvement": "Glycosylation may affect ADA secretion and stability.", "mechanism": "High ADA in pleural fluid is diagnostic for tuberculosis.", "protein": "Adenosine deaminase (ADA)", "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "low", "disease": "Tuberculous pleurisy", "glycan_involvement": "Glycosylation influences LDH secretion and activity.", "mechanism": "Elevated LDH in pleural fluid reflects tissue damage and inflammation.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "medium", "disease": "Hypogammaglobulinemia", "glycan_involvement": "Glycosylation modulates globulin solubility and immune function.", "mechanism": "Low globulin levels reflect urinary loss and immune deficiency in NS.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12380572" }, { "confidence": "high", "disease": "Edema", "glycan_involvement": "Glycosylation may affect albumin half-life and renal handling.", "mechanism": "Hypoalbuminemia reduces plasma oncotic pressure, causing edema.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12380572" }, { "confidence": "medium", "disease": "Ebstein's Anomaly", "glycan_involvement": "Altered glycosylation may affect valve extracellular matrix and function.", "mechanism": "Abnormal glycoprotein composition or structure in the tricuspid valve may contribute to leaflet malformation and displacement.", "protein": "Tricuspid Valve Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12381677" }, { "confidence": "medium", "disease": "Tricuspid Regurgitation", "glycan_involvement": "Glycosylation affects leaflet flexibility and integrity.", "mechanism": "Defective glycoproteins in the valve leaflets impair coaptation, leading to regurgitation.", "protein": "Tricuspid Valve Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12381677" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "BNP is a glycoprotein; glycosylation may affect its stability and detection.", "mechanism": "BNP is elevated in response to ventricular stretch and dysfunction.", "protein": "Brain Natriuretic Peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12381677" }, { "confidence": "high", "disease": "Disseminated Intravascular Coagulation", "glycan_involvement": "Glycosylation is essential for thrombomodulin's anticoagulant function.", "mechanism": "Recombinant thrombomodulin is used to treat DIC by enhancing protein C activation.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381677" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation", "glycan_involvement": "Glycosylation modulates vWF multimerization and activity.", "mechanism": "vWF levels are altered in DIC, reflecting endothelial dysfunction.", "protein": "Von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12381677" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation impacts valve durability and repair.", "mechanism": "Valve glycoprotein defects lead to regurgitation and volume overload, progressing to heart failure.", "protein": "Tricuspid Valve Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12381677" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation is required for therapeutic efficacy.", "mechanism": "Recombinant thrombomodulin is used to modulate coagulation in septic patients.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381677" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22 glycoprotein I affects antigenicity and antibody binding.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are diagnostic markers for APS.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12381687" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates \u03b22 glycoprotein I structure and immune recognition.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies promote endothelial activation and thrombosis.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12381687" }, { "confidence": "medium", "disease": "Bleeding complications (including mucosal/soft-tissue bleeding)", "glycan_involvement": "Altered glycosylation may influence immune complex formation and vascular effects.", "mechanism": "APS patients with anti-\u03b22 glycoprotein I antibodies may develop bleeding due to small-vessel vasculopathy and thrombocytopenia.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12381687" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "MDA5 is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Anti-MDA5 antibodies are highly specific for a DM subtype, indicating disease activity and recurrence.", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "Glycosylation may modulate MDA5 immune interactions.", "mechanism": "Anti-MDA5 antibody positivity is associated with increased risk and severity of ILD in DM patients.", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "medium", "disease": "Cutaneous Ulcer", "glycan_involvement": "Glycosylation may influence MDA5 autoantigenicity in skin.", "mechanism": "Anti-MDA5 antibody-positive DM frequently presents with cutaneous ulcers, which may indicate poor prognosis.", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Glycosylation may affect MDA5 tissue distribution and immune response.", "mechanism": "Anti-MDA5 antibody-positive DM can present with liver dysfunction, especially during disease flares.", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "KL-6 is a mucin-type glycoprotein; its glycosylation is essential for biomarker function.", "mechanism": "Elevated KL-6 levels reflect ILD activity and are used to monitor disease progression.", "protein": "KL-6", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "medium", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Ferritin glycosylation may affect serum stability and immune recognition.", "mechanism": "Serum ferritin levels correlate with disease activity and prognosis in anti-MDA5 antibody-positive DM.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Glycosylation critical for KL-6 detection and function.", "mechanism": "KL-6 is elevated in DM patients with ILD, serving as a marker for lung involvement.", "protein": "KL-6", "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "medium", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Glycosylation may influence antibody binding and therapeutic efficacy.", "mechanism": "Targeting anti-MDA5 antibodies (e.g., with immunosuppressants) is effective in controlling DM flares.", "protein": "MDA5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382313" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "Glycosylation required for KL-6 immunoreactivity.", "mechanism": "High KL-6 levels predict poor prognosis in DM-associated ILD.", "protein": "KL-6", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "medium", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "Glycosylation may affect ferritin's immunogenicity.", "mechanism": "Low serum ferritin levels are common in recurrent anti-MDA5 antibody-positive DM with ILD.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382313" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Mucin-type O-glycosylation is critical for CA125 antigenicity and detection.", "mechanism": "CA125 is synthesized by mesothelial cells and overexpressed in ovarian neoplasms; used for diagnosis and monitoring.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation enables CA125 secretion and stability in circulation.", "mechanism": "CA125 is elevated due to mesothelial cell activation from venous congestion, hydrostatic pressure, and inflammation.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "high", "disease": "Right-sided heart failure", "glycan_involvement": "Glycosylation is essential for CA125's function as a biomarker.", "mechanism": "Right-sided congestion increases CA125 via mesothelial cell activation.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "medium", "disease": "Heart failure with preserved ejection fraction", "glycan_involvement": "O-glycosylation of CA125 is required for its detection.", "mechanism": "Congestion and inflammation in HFpEF stimulate CA125 production.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "medium", "disease": "Congestive states (volume overload)", "glycan_involvement": "Glycosylation supports CA125 secretion.", "mechanism": "Volume overload leads to mesothelial cell activation and CA125 release.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "medium", "disease": "Benign diseases (general)", "glycan_involvement": "Glycosylation is necessary for CA125's antigenic properties.", "mechanism": "CA125 can be elevated in various benign conditions due to mesothelial irritation.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC12382455" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation allows for reliable measurement of CA125 in serum.", "mechanism": "CA125 levels can be used to monitor and tailor diuretic therapy in heart failure.", "protein": "Carbohydrate antigen 125 (CA125)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382455" }, { "confidence": "high", "disease": "Clonorchiasis", "glycan_involvement": "CsESPs are glycoproteins; glycosylation may affect antigenicity and immune recognition.", "mechanism": "CsESPs are used to detect parasite-specific IgG antibodies in host serum and mucosa, indicating infection.", "protein": "Clonorchis sinensis excretory/secretory proteins (CsESPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "high", "disease": "Clonorchiasis", "glycan_involvement": "IgG glycosylation modulates immune effector functions and detection sensitivity.", "mechanism": "Elevated parasite-specific IgG in serum and mucosa correlates with infection and worm burden.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Hepatobiliary disease", "glycan_involvement": "ALT is glycosylated, which may affect stability and secretion.", "mechanism": "Serum ALT levels increase during C. sinensis infection, reflecting hepatocellular damage.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Hepatobiliary disease", "glycan_involvement": "AST glycosylation may influence enzyme activity and release.", "mechanism": "Serum AST levels increase during C. sinensis infection, indicating liver injury.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Cholangiocarcinoma", "glycan_involvement": "Glycosylation of CsESPs may modulate host-pathogen interactions and carcinogenesis.", "mechanism": "Chronic exposure to CsESPs is epidemiologically linked to cholangiocarcinoma development.", "protein": "Clonorchis sinensis excretory/secretory proteins (CsESPs)", "relationship_type": "causal", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Clonorchiasis", "glycan_involvement": "Potential glycosylation may affect channel function and drug binding.", "mechanism": "Targeted by ivermectin, leading to parasite paralysis and death.", "protein": "Glutamate-gated chloride channel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382626" }, { "confidence": "low", "disease": "Cholangiocarcinoma", "glycan_involvement": "Altered IgG glycosylation may influence inflammation and carcinogenesis.", "mechanism": "Persistent IgG response to CsESPs may indicate chronic infection and increased cancer risk.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Hepatobiliary disease", "glycan_involvement": "Glycosylation may affect immunogenicity and fibrogenic potential.", "mechanism": "CsESPs contribute to liver inflammation and fibrosis during infection.", "protein": "Clonorchis sinensis excretory/secretory proteins (CsESPs)", "relationship_type": "causal", "source_pmcid": "PMC12382626" }, { "confidence": "low", "disease": "Hepatobiliary disease", "glycan_involvement": "Glycosylation could modulate channel activity and drug efficacy.", "mechanism": "Ivermectin targeting may reduce parasite-induced liver damage.", "protein": "Glutamate-gated chloride channel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382626" }, { "confidence": "medium", "disease": "Hepatobiliary disease", "glycan_involvement": "IgG glycosylation influences immune response and disease severity.", "mechanism": "Mucosal IgG levels correlate with worm burden and liver pathology.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382626" }, { "confidence": "high", "disease": "Chronic Radiation-Induced Brain Injury (RIBI)", "glycan_involvement": "CD44 function and ligand binding are regulated by N- and O-glycosylation, affecting cell adhesion and migration.", "mechanism": "Serum and hippocampal CD44 levels are elevated in RIBI and reduced by neuroprotective interventions; associated with neuroinflammation and ECM remodeling.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382694" }, { "confidence": "high", "disease": "Cognitive Impairment", "glycan_involvement": "Glycosylation modulates CD44-mediated signaling in neuroinflammation.", "mechanism": "Upregulation of CD44 correlates with neuronal loss and cognitive deficits post-irradiation; reduction improves cognitive outcomes.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382694" }, { "confidence": "medium", "disease": "Chronic Radiation-Induced Brain Injury (RIBI)", "glycan_involvement": "CD74 glycosylation affects its stability and interaction with MIF, modulating immune response.", "mechanism": "CD74 is upregulated in hippocampus after irradiation; reduction by HRW/memantine correlates with reduced neuroinflammation.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382694" }, { "confidence": "medium", "disease": "Chronic Radiation-Induced Brain Injury (RIBI)", "glycan_involvement": "SPP1 is heavily glycosylated, influencing its role in cell signaling and immune modulation.", "mechanism": "SPP1 is upregulated in RIBI and reduced by interventions; involved in neuroinflammation and ECM remodeling.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12382694" }, { "confidence": "medium", "disease": "Chronic Radiation-Induced Brain Injury (RIBI)", "glycan_involvement": "Wnt1 glycosylation is essential for secretion and activity in signaling pathways.", "mechanism": "Wnt1 is upregulated by HRW, promoting neurogenesis and synaptic preservation.", "protein": "Wnt1", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors (Probable). 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Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (PubMe", "gene_name": "WNT1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P04628" }, "relationship_type": "protective", "source_pmcid": "PMC12382694" }, { "confidence": "high", "disease": "Hepatic Ischemia\u2013Reperfusion Injury (IRI)", "glycan_involvement": "Glycosylation modulates CEACAM1's cell adhesion and signaling.", "mechanism": "Regulates S1P\u2013S1PR2/3-dependent NETosis, amplifying neutrophil-mediated liver injury.", "protein": "CEACAM1", "protein_enriched": { "function": "Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and also function", "gene_name": "CEACAM1", "glycan_count": 47, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22572EH", "G49108TO", "G57776ZS", "G80075MS", "G92275SC", "G00912UN", "G05724UK", "G06110VR", "G07246CJ", "G10819WX", "G14669DU", "G27947YN", "G28681TP", "G39188ZX", "G40926MX", "G49906RN", "G59626AS", "G70441OD", "G70619PT", "G79666IR", "G80920RR", "G86880BF", "G87661QW", "G41071NU", "G42124LM", "G23984SE", "G27058EU", "G75983OB", "G83229XP", "G84452RH", "G01650EU", "G02815KT", "G11870QZ", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G43089EG", "G59924QI", "G62765YT", "G64527OM", "G84225JN", "G92050GC", "G92406TI", "G95865ZB", "G25418HZ" ], "uniprot_id": "P13688" }, "relationship_type": "causal", "source_pmcid": "PMC12382767" }, { "confidence": "high", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "CD44 glycosylation affects ligand (hyaluronic acid) binding and nanoparticle targeting.", "mechanism": "CD44-mediated targeting enhances hepatic delivery of ROS-scavenging nanoparticles, reducing inflammation and fibrosis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382767" }, { "confidence": "medium", "disease": "Hepatic Ischemia\u2013Reperfusion Injury (IRI)", "glycan_involvement": "Glycosylation may influence ANXA1 secretion and receptor interaction.", "mechanism": "ANXA1\u2013FPR2 axis modulates LSEC\u2013monocyte crosstalk, reducing inflammation and neutrophil recruitment.", "protein": "ANXA1", "relationship_type": "protective", "source_pmcid": "PMC12382767" }, { "confidence": "high", "disease": "Hepatic Ischemia\u2013Reperfusion Injury (IRI)", "glycan_involvement": "Glycosylation regulates HMGB1 secretion and immune activation.", "mechanism": "HMGB1 release activates TLR4/NF-\u03baB, driving neutrophil recruitment and ROS generation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12382767" }, { "confidence": "high", "disease": "Early Allograft Dysfunction", "glycan_involvement": "TIM4 mucin domain is heavily O-glycosylated, affecting immune recognition.", "mechanism": "High hepatic TIM4 correlates with increased ER stress, apoptosis, and poor graft survival.", "protein": "TIM4", "relationship_type": "biomarker", "source_pmcid": "PMC12382767" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation may regulate FPR2 ligand binding and signaling.", "mechanism": "FPR2 mediates ANXA1 signaling, modulating monocyte recruitment and inflammatory response.", "protein": "FPR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382767" }, { "confidence": "high", "disease": "Hepatic Ischemia\u2013Reperfusion Injury (IRI)", "glycan_involvement": "N-glycosylation is essential for TLR4 surface expression and ligand recognition.", "mechanism": "TLR4 activation by DAMPs (e.g., HMGB1) triggers NF-\u03baB pathway, amplifying inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12382767" }, { "confidence": "medium", "disease": "Neutrophil Extracellular Trap (NET)-associated injury", "glycan_involvement": "Glycosylation may affect SYK stability and signaling.", "mechanism": "SYK inhibition reduces neutrophil recruitment, NET formation, and liver inflammation.", "protein": "SYK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382767" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation may modulate chaperone function.", "mechanism": "Upregulated in LSECs post-reperfusion, associated with heat shock response and endothelial injury.", "protein": "HSPE1", "relationship_type": "biomarker", "source_pmcid": "PMC12382767" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation may influence BAG3 stability and interactions.", "mechanism": "Upregulated in LSECs after IRI, linked to cell cycle control and homeostasis disruption.", "protein": "BAG3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382767" }, { "confidence": "high", "disease": "Multidrug-resistant Escherichia coli infection", "glycan_involvement": "Glycosylation may affect ESBL folding and secretion.", "mechanism": "ESBLs hydrolyze third-generation cephalosporins, conferring resistance.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "causal", "source_pmcid": "PMC12382820" }, { "confidence": "high", "disease": "Multidrug-resistant Klebsiella pneumoniae infection", "glycan_involvement": "Glycosylation may modulate enzyme stability.", "mechanism": "ESBLs confer resistance to beta-lactam antibiotics.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "causal", "source_pmcid": "PMC12382820" }, { "confidence": "high", "disease": "Multidrug-resistant Klebsiella pneumoniae infection", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "Carbapenemases hydrolyze carbapenems, leading to resistance.", "protein": "Carbapenemases", "relationship_type": "causal", "source_pmcid": "PMC12382820" }, { "confidence": "high", "disease": "Multidrug-resistant Escherichia coli infection", "glycan_involvement": "Glycosylation may affect secretion and function.", "mechanism": "Carbapenemases confer resistance to carbapenem antibiotics.", "protein": "Carbapenemases", "relationship_type": "causal", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Bloodstream infection", "glycan_involvement": "Glycosylation may affect ESBL localization.", "mechanism": "Presence of ESBLs in E. coli is associated with bloodstream infections.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "biomarker", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Urinary tract infection", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "ESBL-producing E. coli/K. pneumoniae are common in UTIs.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "biomarker", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Carbapenemase-producing K. pneumoniae associated with pneumonia.", "protein": "Carbapenemases", "relationship_type": "biomarker", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation may influence enzyme secretion.", "mechanism": "ESBL-producing K. pneumoniae linked to pneumonia cases.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "biomarker", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Bloodstream infection", "glycan_involvement": "Glycosylation may affect enzyme function.", "mechanism": "Carbapenemase-producing E. coli/K. pneumoniae found in bloodstream infections.", "protein": "Carbapenemases", "relationship_type": "biomarker", "source_pmcid": "PMC12382820" }, { "confidence": "medium", "disease": "Multidrug-resistant Escherichia coli infection", "glycan_involvement": "Glycosylation could be targeted to inhibit ESBL function.", "mechanism": "Targeting ESBLs may restore antibiotic efficacy.", "protein": "Extended-spectrum beta-lactamases (ESBLs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382820" }, { "confidence": "high", "disease": "Equine Herpesvirus Type 1 (EHV-1) Infection", "glycan_involvement": "gB is a glycosylated envelope protein essential for viral entry and spread.", "mechanism": "gB gene is detected by PCR as a marker of EHV-1 infection in horses.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382900" }, { "confidence": "high", "disease": "Equine Herpes Myeloencephalopathy (EHM)", "glycan_involvement": "Glycosylation of gB is critical for its function in membrane fusion and immune evasion.", "mechanism": "gB mediates viral entry into host cells, facilitating neuroinvasion and development of EHM.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382900" }, { "confidence": "medium", "disease": "Equine Abortion", "glycan_involvement": "Glycosylation of gB may influence tissue tropism and immune escape.", "mechanism": "gB enables EHV-1 to infect placental tissues, leading to abortion.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382900" }, { "confidence": "medium", "disease": "Equine Herpesvirus Type 1 (EHV-1) Infection", "glycan_involvement": "Glycosylation may affect drug binding and efficacy.", "mechanism": "gB is targeted by antiviral drugs (e.g., acyclovir) to inhibit viral replication.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382900" }, { "confidence": "medium", "disease": "Equine Herpesvirus Type 1 (EHV-1) Infection", "glycan_involvement": "Glycosylation of gB affects antigenicity and antibody recognition.", "mechanism": "Seroneutralization assays detect antibodies against gB, indicating exposure or immunity.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382900" }, { "confidence": "high", "disease": "Aleutian mink disease", "glycan_involvement": "IgG glycosylation affects immune complex formation and clearance.", "mechanism": "High IgG levels form immune complexes that deposit in organs, causing pathology.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12382955" }, { "confidence": "high", "disease": "Aleutian mink disease", "glycan_involvement": "IgM glycosylation modulates its immunogenicity and complex formation.", "mechanism": "Anti-IgM antibody therapy suppresses pathogenic antibody production, reducing immune complex formation.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Aleutian mink disease", "glycan_involvement": "Glycosylation of VLA-4 is essential for its cell adhesion function.", "mechanism": "Mycophenolic acid reduces fucose/mannose transfer to glycoproteins, impeding VLA-4 production and leukocyte adhesion.", "protein": "Integrin VLA-4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Hepatitis B virus infection", "glycan_involvement": "Indirect; CypA interacts with glycoproteins during viral replication.", "mechanism": "CypA is required for viral replication; cyclophilin inhibitors block replication.", "protein": "Cyclophilin A (CypA)", "protein_enriched": { "function": "Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic", "gene_name": "PPIA", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27915IV", "G37995HC", "G49906RN", "G60033FS", "G62765YT", "G49108TO", "G70994MS", "G80920RR" ], "uniprot_id": "P62937" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Aleutian mink disease", "glycan_involvement": "Potential glycosylation affects antigenicity and immune recognition.", "mechanism": "VP2 sequence variation determines AMDV strain virulence and tissue tropism.", "protein": "VP2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Aleutian mink disease", "glycan_involvement": "IMPDH inhibition reduces glycoprotein synthesis (fucose/mannose transfer).", "mechanism": "Mycophenolic acid inhibits IMPDH, reducing lymphocyte proliferation and antibody production.", "protein": "IMPDH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Autoimmune diseases (general)", "glycan_involvement": "NF-\u03baB regulates glycoprotein expression (cytokines, adhesion molecules).", "mechanism": "Corticosteroids inhibit NF-\u03baB, reducing pro-inflammatory cytokine and adhesion protein synthesis.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Aleutian mink disease", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "Gold nanoparticles inhibit IL-1\u03b2 production, reducing inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation of TNF-\u03b1 and antibodies affects efficacy and immune modulation.", "mechanism": "Anti-TNF-\u03b1 monoclonal antibodies block inflammatory signaling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "medium", "disease": "Graft-versus-host disease", "glycan_involvement": "CD25 glycosylation modulates receptor function and antibody binding.", "mechanism": "Anti-CD25 monoclonal antibodies inhibit T cell activation, reducing immune response.", "protein": "CD25 (IL-2 receptor alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382955" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Haptoglobin is a glycoprotein; glycosylation affects its stability and immune functions.", "mechanism": "Increased haptoglobin expression and altered localization in intestinal tissue after ozone exposure correlates with chronic inflammation and barrier dysfunction characteristic of IBD.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Celiac Disease", "glycan_involvement": "Zonulin is a glycoprotein; glycosylation is required for secretion and function.", "mechanism": "Elevated zonulin increases intestinal permeability, facilitating antigen translocation and autoimmune activation in celiac disease.", "protein": "Zonulin (Prehaptoglobin-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Increased Intestinal Permeability ('Leaky Gut')", "glycan_involvement": "Glycosylation is essential for zonulin's structure and activity.", "mechanism": "Zonulin modulates tight junctions, and its upregulation leads to reversible disassembly, increasing permeability.", "protein": "Zonulin (Prehaptoglobin-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382992" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation modulates haptoglobin's anti-inflammatory and antioxidant properties.", "mechanism": "Haptoglobin is an acute-phase glycoprotein upregulated during chronic inflammation, including in the gut after ozone exposure.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "IL-1\u03b2 is glycosylated, which affects secretion and receptor interactions.", "mechanism": "IL-1\u03b2 is upregulated in intestinal tissue during chronic ozone exposure, promoting inflammation and tissue damage as seen in IBD.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "IL-6 glycosylation is important for stability and bioactivity.", "mechanism": "IL-6 is increased in the intestine after ozone exposure, driving leukocyte recruitment and chronic inflammation in IBD.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation is necessary for zonulin's function in tight junction regulation.", "mechanism": "Zonulin-mediated tight junction disruption increases permeability, allowing antigen influx and perpetuating inflammation in IBD.", "protein": "Zonulin (Prehaptoglobin-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382992" }, { "confidence": "medium", "disease": "Increased Intestinal Permeability ('Leaky Gut')", "glycan_involvement": "Glycosylation affects haptoglobin's localization and function at the epithelial barrier.", "mechanism": "Altered haptoglobin localization in enterocytes and lamina propria correlates with disrupted barrier function.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382992" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation modulates IL-6 secretion and receptor binding.", "mechanism": "IL-6 is upregulated in response to oxidative stress and is a marker of ongoing inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382992" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation influences IL-1\u03b2 processing and activity.", "mechanism": "IL-1\u03b2 elevation reflects activation of innate immune responses and tissue inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382992" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Glycosylation required for TSP1 secretion and matrix interactions.", "mechanism": "TSP1 upregulated in senescent cells, amplifies oxidative stress and DNA damage via CD47-Nox1 axis, reinforcing senescence and tissue aging.", "protein": "Thrombospondin-1 (TSP1)", "relationship_type": "causal", "source_pmcid": "PMC12383077" }, { "confidence": "high", "disease": "Impaired angiogenesis", "glycan_involvement": "Glycosylation modulates TSP1 binding to CD47 and ECM.", "mechanism": "TSP1-CD47 signaling inhibits nitric oxide pathway, reducing angiogenesis and vascular repair in aging tissues.", "protein": "Thrombospondin-1 (TSP1)", "relationship_type": "causal", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Immune evasion", "glycan_involvement": "Glycosylation affects CD47 cell surface expression and ligand binding.", "mechanism": "CD47 engagement by TSP1 promotes ROS production, suppresses immune clearance of senescent cells.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "causal", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "N-glycosylation essential for transferrin stability and iron binding.", "mechanism": "Transferrin binds iron, limits Fenton chemistry and ROS formation, reducing oxidative stress in aging.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "protective", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ceruloplasmin secretion and activity.", "mechanism": "Ceruloplasmin binds copper, prevents ROS generation, protecting vascular tissues.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "protective", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation influences albumin antioxidant capacity.", "mechanism": "Albumin binds transition metals, reduces ROS, and limits inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Tissue degeneration", "glycan_involvement": "Glycosylation regulates MMP1 secretion and activity.", "mechanism": "MMP1 secreted in SASP degrades extracellular matrix, promoting tissue degeneration in aging and disease.", "protein": "Matrix metalloproteinase 1 (MMP1)", "relationship_type": "causal", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates VEGF receptor binding and bioactivity.", "mechanism": "VEGF in SASP promotes angiogenesis and tumor progression.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation required for IL-6 secretion and receptor interaction.", "mechanism": "IL-6 secreted in SASP drives systemic inflammation and age-related disease.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383077" }, { "confidence": "medium", "disease": "Tissue degeneration", "glycan_involvement": "Glycosylation affects MMP3 stability and function.", "mechanism": "MMP3 in SASP degrades ECM, contributing to tissue remodeling and degeneration.", "protein": "Matrix metalloproteinase 3 (MMP3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383077" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CD36 is a glycoprotein; glycosylation affects its membrane localization and ligand binding.", "mechanism": "CD36 mediates uptake of oxLDL and MDA-LDL by macrophages, promoting foam cell formation and plaque development.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12383103" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates CD36 stability and function in metabolic tissues.", "mechanism": "CD36 overexpression is linked to insulin resistance via increased fatty acid uptake and lipid-induced metabolic dysfunction.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12383103" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "sCD36 retains glycosylation from membrane CD36, influencing its stability in plasma.", "mechanism": "Elevated sCD36 levels reflect endothelial activation and atherosclerosis progression in diabetic patients with STEMI.", "protein": "soluble CD36 (sCD36)", "relationship_type": "biomarker", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects CD36 trafficking and lipid uptake.", "mechanism": "CD36 expression is upregulated in obesity, contributing to dyslipidemia and increased cardiovascular risk.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12383103" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycan modifications influence susceptibility to oxidation and recognition by CD36.", "mechanism": "oxLDL is taken up by CD36, leading to foam cell formation and vascular inflammation.", "protein": "Oxidized LDL (oxLDL)", "relationship_type": "causal", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "MDA modification alters LDL glycan structure, increasing CD36-mediated uptake.", "mechanism": "Elevated MDA-LDL is a marker of lipid peroxidation and oxidative stress, associated with coronary artery disease in T2DM.", "protein": "MDA-LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation regulates CD36 function in adipose and muscle tissues.", "mechanism": "CD36 facilitates fatty acid uptake, contributing to lipid-induced insulin resistance.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Variant may affect glycosylation and splicing, altering CD36 function.", "mechanism": "CD36 gene variant rs3173798 T/T is an independent risk factor for STEMI in T2DM patients.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation maintains sCD36 stability in circulation.", "mechanism": "sCD36 levels correlate with carotid intima-media thickening, a preclinical marker of atherosclerosis.", "protein": "soluble CD36 (sCD36)", "relationship_type": "biomarker", "source_pmcid": "PMC12383103" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Targeting glycosylation may modulate CD36 activity and disease progression.", "mechanism": "CD36 is proposed as a molecular target for antioxidant defense in T2DM-associated cardiovascular disease.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383103" }, { "confidence": "high", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "CD44 is a heavily glycosylated cell surface protein; glycosylation modulates ligand binding and signaling.", "mechanism": "CD44 overexpression increases endothelial permeability and inflammatory cytokine secretion in response to GPS infection.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383133" }, { "confidence": "high", "disease": "Gl\u00e4sser\u2019s disease", "glycan_involvement": "Glycosylation of CD44 affects its interaction with hyaluronan and other ligands.", "mechanism": "GPS infection upregulates CD44 in porcine endothelial cells, correlating with disease severity.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383133" }, { "confidence": "high", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "Glycosylation status may influence CD44\u2019s role as a therapeutic target.", "mechanism": "CD44 silencing reduces GPS-induced permeability and inflammatory protein expression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383133" }, { "confidence": "high", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "VEGFA is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "GPS infection increases VEGFA expression, promoting endothelial permeability.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383133" }, { "confidence": "medium", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "MMP-3 is glycosylated; glycosylation modulates enzyme activity.", "mechanism": "GPS infection upregulates MMP-3, contributing to barrier disruption.", "protein": "MMP-3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383133" }, { "confidence": "medium", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "MMP-9 glycosylation affects stability and activity.", "mechanism": "GPS infection increases MMP-9, leading to extracellular matrix degradation and increased permeability.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12383133" }, { "confidence": "medium", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "No direct glycosylation; interacts with glycoprotein signaling complexes.", "mechanism": "GPS infection upregulates c-Src, activating signaling pathways that increase permeability.", "protein": "c-Src", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383133" }, { "confidence": "medium", "disease": "sepsis", "glycan_involvement": "Soluble CD44 glycosylation influences detection and function.", "mechanism": "Soluble CD44 levels are elevated in sepsis models, correlating with endothelial dysfunction.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383133" }, { "confidence": "high", "disease": "vascular endothelial hyperpermeability", "glycan_involvement": "Luteolin may affect CD44 glycosylation or signaling.", "mechanism": "Luteolin treatment suppresses CD44 pathway, reducing GPS-induced permeability.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12383133" }, { "confidence": "medium", "disease": "Gl\u00e4sser\u2019s disease", "glycan_involvement": "VEGFA glycosylation modulates its activity in disease.", "mechanism": "VEGFA upregulation is associated with GPS-induced vascular injury.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383133" }, { "confidence": "high", "disease": "von Willebrand disease (vWD)", "glycan_involvement": "vWF is a heavily glycosylated multimer; glycosylation critical for multimerization and function.", "mechanism": "Deficiency or dysfunction of vWF impairs platelet adhesion and FVIII stabilization, causing bleeding.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12383335" }, { "confidence": "high", "disease": "Acquired von Willebrand disease (AVWD)", "glycan_involvement": "Glycosylation affects vWF clearance and immune recognition.", "mechanism": "Autoantibodies or adsorption reduce vWF levels/activity, leading to bleeding; vWF replacement and immunotherapy are used.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation required for FVIII secretion, stability, and activity.", "mechanism": "Deficiency or dysfunction of FVIII causes impaired coagulation; FVIII replacement is standard therapy.", "protein": "Factor VIII", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "N-glycosylation important for FIX secretion and function.", "mechanism": "Deficiency or dysfunction of FIX impairs coagulation; FIX replacement is standard therapy.", "protein": "Factor IX", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Glycosylation required for ligand binding and cell surface expression.", "mechanism": "P-selectin mediates leukocyte and platelet adhesion, driving vaso-occlusion; targeted by crizanlizumab.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Glycosylation modulates ligand interactions.", "mechanism": "E-selectin promotes leukocyte adhesion in inflammation and VOC; inhibitors under development.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "N-glycosylation affects ligand binding and cell adhesion.", "mechanism": "VCAM-1 mediates leukocyte-endothelial adhesion, contributing to VOC.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "medium", "disease": "Rare bleeding disorders (RBDs)", "glycan_involvement": "Glycosylation affects secretion and half-life.", "mechanism": "Deficiency causes hemophilia C; FXI replacement or antisense oligonucleotides used therapeutically.", "protein": "Factor XI", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "medium", "disease": "Rare bleeding disorders (RBDs)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Deficiency leads to severe bleeding; FXIII concentrate used for prophylaxis.", "protein": "Factor XIII", "protein_enriched": { "function": "Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin ", "gene_name": "F13A1", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G13456GP", "G85677PP", "G49108TO" ], "uniprot_id": "P00488" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383335" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy (TMA)", "glycan_involvement": "Multimerization and glycosylation status influence prothrombotic activity.", "mechanism": "High-molecular-weight vWF multimers contribute to microvascular thrombosis in TMA.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383335" }, { "confidence": "high", "disease": "Glaucoma", "glycan_involvement": "ATX is a secreted glycoprotein; glycosylation is essential for secretion and enzymatic activity.", "mechanism": "ATX generates LPA, activating RhoA/ROCK pathway, promoting TM cell contractility and ECM accumulation, increasing IOP.", "protein": "Autotaxin (ATX)", "protein_enriched": { "function": "Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751,", "gene_name": "ENPP2", "glycan_count": 18, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G22310AV", "G43769HG", "G45395BF", "G47748JZ", "G48414YA", "G51653BI", "G59626AS", "G62765YT", "G80920RR", "G83460ZZ", "G84452RH", "G47410OF", "G91845HM", "G04657PL", "G34989PA", "G43669FQ" ], "uniprot_id": "Q13822" }, "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "high", "disease": "Steroid-induced Glaucoma", "glycan_involvement": "Glycosylation regulates ATX secretion and function.", "mechanism": "Steroids upregulate ATX in TM cells, increasing LPA and activating ROCK, leading to fibrotic changes and outflow resistance.", "protein": "Autotaxin (ATX)", "protein_enriched": { "function": "Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751,", "gene_name": "ENPP2", "glycan_count": 18, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G22310AV", "G43769HG", "G45395BF", "G47748JZ", "G48414YA", "G51653BI", "G59626AS", "G62765YT", "G80920RR", "G83460ZZ", "G84452RH", "G47410OF", "G91845HM", "G04657PL", "G34989PA", "G43669FQ" ], "uniprot_id": "Q13822" }, "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "high", "disease": "Fibrosis after Trabeculectomy", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "TGF-\u03b21 induces myofibroblast transdifferentiation and Smad2/3 signaling, promoting fibrosis in conjunctival and Tenon's capsule fibroblasts.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "LPARs are membrane glycoproteins; glycosylation influences receptor localization and ligand binding.", "mechanism": "LPA binds LPAR1/3 on TM cells, activating RhoA/ROCK, increasing cell contractility and ECM deposition.", "protein": "LPAR1/LPAR3", "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation modulates stability and activity.", "mechanism": "Elevated IL-6 in aqueous humor is associated with progression and surgical failure in glaucoma.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "IL-8 glycosylation affects secretion and chemotactic activity.", "mechanism": "Increased IL-8 correlates with inflammation and progression in glaucoma.", "protein": "Interleukin-8 (IL-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Neovascular Glaucoma", "glycan_involvement": "Glycosylation required for ATX function.", "mechanism": "ATX\u2013LPA\u2013ROCK pathway activation contributes to TM fibrosis and outflow resistance in neovascular glaucoma.", "protein": "Autotaxin (ATX)", "protein_enriched": { "function": "Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751,", "gene_name": "ENPP2", "glycan_count": 18, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G22310AV", "G43769HG", "G45395BF", "G47748JZ", "G48414YA", "G51653BI", "G59626AS", "G62765YT", "G80920RR", "G83460ZZ", "G84452RH", "G47410OF", "G91845HM", "G04657PL", "G34989PA", "G43669FQ" ], "uniprot_id": "Q13822" }, "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "high", "disease": "Glaucoma", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 secretion and activity.", "mechanism": "TGF-\u03b21 promotes ECM production and TM fibrosis, increasing outflow resistance and IOP.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Retinal Ganglion Cell Loss", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ROCK inhibition reduces caspase-3 activation, decreasing RGC apoptosis.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383500" }, { "confidence": "medium", "disease": "Optic Nerve Injury", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ROCK inhibitors upregulate Bcl-2, promoting RGC survival after injury.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12383500" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "SHBG glycosylation affects its stability and hormone binding.", "mechanism": "SHBG levels are altered in PCOS, reflecting androgen excess and metabolic dysfunction.", "protein": "Sex Hormone Binding Globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "AMH is a glycoprotein; glycosylation affects its secretion and bioactivity.", "mechanism": "AMH levels are elevated in PCOS and correlate with androgen levels and ovarian morphology.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Minor glycosylation in plasma form; not central to function.", "mechanism": "ALT is a component of the FIB-4 index, elevated in MASLD and liver injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Minor glycosylation in plasma form; not central to function.", "mechanism": "AST is a component of the FIB-4 index, elevated in MASLD and liver injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation and clearance.", "mechanism": "Platelet count is used in FIB-4 index; low platelets reflect advanced fibrosis.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Proinsulin glycosylation affects folding and secretion.", "mechanism": "Insulin resistance is central to PCOS and MASLD pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates SHBG half-life and function.", "mechanism": "Low SHBG is associated with increased risk of MASLD in PCOS.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects AMH stability and activity.", "mechanism": "AMH correlates with androgen levels and may indicate MASLD risk in PCOS.", "protein": "AMH", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Carrier-bound; glycoprotein carriers affect transport.", "mechanism": "Elevated DHEAS is a marker of hyperandrogenism in PCOS.", "protein": "DHEAS", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Carrier-bound; glycoprotein carriers affect transport.", "mechanism": "Elevated androstenedione reflects androgen excess in PCOS.", "protein": "Androstenedione", "relationship_type": "biomarker", "source_pmcid": "PMC12383516" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "NOTCH2 is a glycoprotein; glycosylation is essential for its ligand binding and signaling activity.", "mechanism": "NOTCH2 is upregulated in NAFLD and promotes disease progression by enhancing inflammation and fibrosis.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383517" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation modulates NOTCH2 receptor activation.", "mechanism": "Elevated NOTCH2 expression is associated with progression from steatosis to NASH.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383517" }, { "confidence": "medium", "disease": "NAFLD-related cirrhosis", "glycan_involvement": "Glycosylation required for NOTCH2 function in fibrosis.", "mechanism": "NOTCH2 expression remains high in cirrhosis, reflecting ongoing fibrogenic signaling.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383517" }, { "confidence": "medium", "disease": "Simple steatosis", "glycan_involvement": "Glycosylation status not stage-specific but required for function.", "mechanism": "NOTCH2 is elevated in simple steatosis compared to controls, but less than in advanced stages.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383517" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences NOTCH2-mediated oncogenic signaling.", "mechanism": "Chronic NOTCH2 activation may contribute to HCC development in NAFLD progression.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12383517" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "HA binds host cell sialic acid glycans; glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry by binding sialic acid receptors on host cells, initiating infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Zinc-induced conformational changes in HA disrupt its ability to bind sialic acid glycans.", "mechanism": "Zinc ions inactivate HA, preventing receptor binding and viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Prevents HA-sialic acid glycan interaction, blocking infection at entry.", "mechanism": "Zinc-embedded PPE inactivates HA, providing passive antiviral protection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Assay depends on HA binding to sialic acid glycans on RBCs.", "mechanism": "HA activity measured by hemagglutination assay reflects viral infectivity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383525" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation is critical for receptor binding; zinc may disrupt glycoprotein structure.", "mechanism": "Zinc ions can inactivate spike protein, reducing viral infectivity (cited from previous work).", "protein": "Spike protein (SARS-CoV-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Glycosylation sites on HA influence antigenicity and immune escape.", "mechanism": "Antigenic shift in HA gene drives emergence of pandemic IAV strains.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Glycosylation affects antibody recognition and neutralization.", "mechanism": "Antibodies and ion channel inhibitors target HA to prevent infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Prevents HA from binding host sialic acid glycans.", "mechanism": "Zinc ions induce irreversible HA structural changes, blocking infection for at least 24h.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12383525" }, { "confidence": "medium", "disease": "Influenza (Flu)", "glycan_involvement": "Structural changes near receptor binding domain affect glycan interaction.", "mechanism": "Zinc ions bind to Glu68 and His137 in HA1, inducing conformational changes that mimic fusion-triggering acidic pH.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383525" }, { "confidence": "medium", "disease": "Influenza (Flu)", "glycan_involvement": "Sustained disruption of HA-glycan binding prevents viral adaptation.", "mechanism": "No resistance to zinc-mediated HA inactivation observed after serial viral passaging.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12383525" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoprotein complex; glycosylation of associated proteins is critical for stability.", "mechanism": "Loss of dystrophin disrupts the dystrophin\u2013glycoprotein complex, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Limb-Girdle Muscular Dystrophy (LGMD R3)", "glycan_involvement": "SGCA is a glycoprotein; glycosylation required for membrane localization and function.", "mechanism": "Mutations in SGCA impair sarcoglycan complex, causing muscle weakness.", "protein": "Alpha-sarcoglycan (SGCA)", "protein_enriched": { "function": "Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix", "gene_name": "SGCA", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q16586" }, "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Dysferlinopathy", "glycan_involvement": "Dysferlin is glycosylated; glycosylation affects stability and trafficking.", "mechanism": "Dysferlin deficiency impairs membrane repair in muscle fibers.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Congenital Myopathies", "glycan_involvement": "Laminin glycosylation modulates cell adhesion and signaling.", "mechanism": "Laminin mutations disrupt extracellular matrix, affecting muscle integrity.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Danon Disease", "glycan_involvement": "LAMP2 is heavily glycosylated; glycosylation is essential for lysosomal targeting.", "mechanism": "LAMP2 deficiency impairs lysosomal function, leading to glycogen accumulation.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Cavin-4 glycosylation may affect membrane association.", "mechanism": "Full-length dystrophin restores sarcolemmal localization of cavin-4, normalizing ERK1/2 signaling.", "protein": "Cavin-4", "protein_enriched": { "function": "Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic", "gene_name": "THEM4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5T1C6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "GALGT2 catalyzes O-glycosylation of \u03b1-dystroglycan and other proteins.", "mechanism": "GALGT2 overexpression increases glycosylation of muscle proteins, stabilizing the dystrophin complex and mitigating cardiomyopathy.", "protein": "GALGT2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383629" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "CD63 is glycosylated; glycosylation may influence exosome targeting.", "mechanism": "CD63-modified exosomes enhance muscle cell uptake and gene delivery.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383629" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Integrins are glycoproteins; glycosylation modulates ligand binding.", "mechanism": "AAV vectors engineered to target \u03b1V\u03b26 enhance skeletal muscle gene delivery.", "protein": "Integrin alphaVbeta6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Pompe Disease", "glycan_involvement": "GAA is N-glycosylated; glycosylation required for lysosomal targeting and activity.", "mechanism": "GAA deficiency leads to lysosomal glycogen accumulation and muscle pathology.", "protein": "Acid alpha-glucosidase (GAA)", "relationship_type": "causal", "source_pmcid": "PMC12383629" }, { "confidence": "high", "disease": "Nephrotic Syndrome", "glycan_involvement": "Nephrin is N-glycosylated; glycosylation is essential for its proper folding and function.", "mechanism": "Mutations in NPHS1 gene encoding nephrin disrupt slit diaphragm integrity, leading to proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Nephrotic Syndrome", "glycan_involvement": "Podocin is glycosylated; glycosylation affects membrane localization.", "mechanism": "Mutations in NPHS2 gene encoding podocin impair podocyte function and filtration barrier.", "protein": "Podocin", "protein_enriched": { "function": "Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton", "gene_name": "NPHS2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP85" }, "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Familial LCAT Deficiency", "glycan_involvement": "LCAT is glycosylated; glycosylation affects enzyme stability and secretion.", "mechanism": "LCAT mutations cause defective cholesterol esterification, leading to lipid accumulation and glomerular injury.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Fish-Eye Disease", "glycan_involvement": "Glycosylation status may modulate residual enzyme activity.", "mechanism": "Partial LCAT deficiency leads to unesterified cholesterol accumulation, foam cell formation, and nephrotic syndrome.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Alport Syndrome", "glycan_involvement": "Collagen IV is glycosylated; glycosylation is critical for basement membrane assembly.", "mechanism": "Mutations in collagen IV genes disrupt basement membrane structure, causing hereditary nephritis and proteinuria.", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "medium", "disease": "Congenital Disorders of Glycosylation", "glycan_involvement": "Integrins require N-glycosylation for function.", "mechanism": "Defective glycosylation impairs integrin-mediated cell adhesion, affecting nephron maturation and glomerular filtration.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "medium", "disease": "Fish-Eye Disease", "glycan_involvement": "Abnormal glycosylation leads to glycolipid accumulation.", "mechanism": "Glycosylceramide deposition in glomeruli contributes to proteinuria and nephrotic syndrome.", "protein": "Glycosylceramide", "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "medium", "disease": "Nephrotic Syndrome", "glycan_involvement": "CD80 is glycosylated; glycosylation may affect immune signaling.", "mechanism": "High CD80 expression on podocytes correlates with NS activity.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Membranous Nephropathy", "glycan_involvement": "PLA2R glycosylation may influence antigenicity.", "mechanism": "Autoantibodies against PLA2R glycoprotein are implicated in pathogenesis.", "protein": "PLA2R", "protein_enriched": { "function": "Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response (PubMed:10066756, PubMed:16371369, PubMed:17090529, Pu", "gene_name": "PLA2G7", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q13093" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Schimke Immuno-Osseous Dysplasia", "glycan_involvement": "Indirect; affects transcription of glycoprotein genes.", "mechanism": "SMARCAL1 mutations disrupt chromatin remodeling, impairing podocyte development and leading to FSGS and NS.", "protein": "SMARCAL1", "protein_enriched": { "function": "ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stabl", "gene_name": "SMARCAL1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72667IM", "G80920RR", "G49108TO" ], "uniprot_id": "Q9NZC9" }, "relationship_type": "causal", "source_pmcid": "PMC12383661" }, { "confidence": "high", "disease": "Postoperative atrial fibrillation (POAF)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function as an inflammatory marker.", "mechanism": "CRP levels rise post-surgery, indicating systemic inflammation linked to POAF risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Pericarditis", "glycan_involvement": "NLRP3 and associated proteins may be glycosylated, influencing inflammasome assembly and activation.", "mechanism": "Activation of NLRP3 inflammasome in pericardial mesothelial cells drives local inflammation (pericarditis) after cardiac surgery.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Postoperative atrial fibrillation (POAF)", "glycan_involvement": "Glycosylation may modulate inflammasome activity and downstream cytokine release.", "mechanism": "Upregulation of NLRP3 inflammasome contributes to POAF development via inflammatory signaling.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12383744" }, { "confidence": "high", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation is essential for CRP's solubility and function.", "mechanism": "CRP is used to monitor SIRS severity post-cardiac surgery.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Pericarditis", "glycan_involvement": "Glycoprotein integrity is crucial for anti-inflammatory barrier function.", "mechanism": "Damage to mesothelial cell glycoproteins triggers local pericardial inflammation.", "protein": "Pericardial mesothelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383744" }, { "confidence": "low", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation may regulate inflammasome protein interactions.", "mechanism": "NLRP3 activation amplifies systemic inflammation after CPB.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Pericarditis", "glycan_involvement": "Glycosylation affects CRP's detection and clearance.", "mechanism": "CRP elevation reflects pericardial inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Postoperative atrial fibrillation (POAF)", "glycan_involvement": "Potential modulation of glycosylated inflammasome components.", "mechanism": "Colchicine inhibits NLRP3 activation, reducing POAF incidence.", "protein": "NLRP3 inflammasome", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383744" }, { "confidence": "medium", "disease": "Postoperative atrial fibrillation (POAF)", "glycan_involvement": "Glycosylation status may affect CRP's anti-inflammatory properties.", "mechanism": "Lower CRP levels post-colchicine therapy correlate with reduced POAF risk.", "protein": "C-reactive protein", "relationship_type": "protective", "source_pmcid": "PMC12383744" }, { "confidence": "low", "disease": "Postoperative atrial fibrillation (POAF)", "glycan_involvement": "Loss or modification of glycosylation disrupts mesothelial cell function.", "mechanism": "Surgical trauma to glycoproteins increases local inflammation, predisposing to POAF.", "protein": "Pericardial mesothelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383744" }, { "confidence": "high", "disease": "Adrenomyeloneuropathy (AMN)", "glycan_involvement": "MAG is a glycoprotein essential for myelin stability; glycosylation affects its function.", "mechanism": "MAG promoter drives ABCD1 expression in oligodendrocytes, preventing axonal degeneration.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "Adrenomyeloneuropathy (AMN)", "glycan_involvement": "APP is heavily glycosylated, which modulates its trafficking and aggregation.", "mechanism": "APP clusters in axons indicate defective axonal transport in AMN mouse model.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC12383759" }, { "confidence": "high", "disease": "X-linked adrenoleukodystrophy (X-ALD)", "glycan_involvement": "ALDP is glycosylated; glycosylation may affect peroxisomal localization and function.", "mechanism": "Loss-of-function mutations in ABCD1 gene encoding ALDP cause VLCFA accumulation and neurodegeneration.", "protein": "Adrenoleukodystrophy protein (ALDP)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed", "gene_name": "ABCD1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P33897" }, "relationship_type": "causal", "source_pmcid": "PMC12383759" }, { "confidence": "high", "disease": "Adrenomyeloneuropathy (AMN)", "glycan_involvement": "Glycosylation may regulate ALDP stability and trafficking.", "mechanism": "Deficiency of ALDP in oligodendrocytes leads to impaired VLCFA degradation and axonopathy.", "protein": "Adrenoleukodystrophy protein (ALDP)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed", "gene_name": "ABCD1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P33897" }, "relationship_type": "causal", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "X-linked adrenoleukodystrophy (X-ALD)", "glycan_involvement": "Glycosylation status may affect compensatory function.", "mechanism": "ALDR (ABCD2) can partially compensate for ALDP deficiency in VLCFA transport.", "protein": "Adrenoleukodystrophy-related protein (ALDR)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:21145416, PubMed", "gene_name": "ABCD2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9UBJ2" }, "relationship_type": "protective", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "X-linked adrenoleukodystrophy (X-ALD)", "glycan_involvement": "Glycosylation may influence transporter activity.", "mechanism": "PMP70 (ABCD3) also shuttles VLCFA into peroxisomes, partially compensating for ALDP loss.", "protein": "PMP70", "protein_enriched": { "function": "Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-", "gene_name": "ABCD3", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P28288" }, "relationship_type": "protective", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "MAG glycosylation is critical for Schwann cell myelin function.", "mechanism": "MAG promoter used to drive ABCD1 expression in Schwann cells to rescue peripheral neuropathy.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "Adrenal insufficiency", "glycan_involvement": "Glycosylation may affect ALDP function in adrenal cells.", "mechanism": "ALDP deficiency leads to VLCFA accumulation in adrenal cortex, causing cell apoptosis and insufficiency.", "protein": "Adrenoleukodystrophy protein (ALDP)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed", "gene_name": "ABCD1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P33897" }, "relationship_type": "causal", "source_pmcid": "PMC12383759" }, { "confidence": "medium", "disease": "Cerebral adrenoleukodystrophy (cALD)", "glycan_involvement": "MAG glycosylation is essential for CNS myelin integrity.", "mechanism": "MAG promoter-driven gene therapy may target oligodendrocytes in cerebral white matter.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383759" }, { "confidence": "low", "disease": "Cerebral adrenoleukodystrophy (cALD)", "glycan_involvement": "APP glycosylation modulates aggregation and neurotoxicity.", "mechanism": "APP clusters may indicate axonal transport defects in cALD.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC12383759" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "MFAP2 is an ECM glycoprotein; glycosylation may affect its interaction with fibrillin and TGF-\u03b2 sequestration.", "mechanism": "MFAP2 modulates TGF-\u03b2 signaling in the extracellular matrix, influencing immune regulation and inflammation.", "protein": "MFAP2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation affects IL6R stability and ligand binding.", "mechanism": "IL6R mediates IL-6 signaling; soluble and membrane forms have opposing roles in inflammation.", "protein": "IL6R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "CD40 is a glycoprotein; glycosylation modulates receptor-ligand interactions.", "mechanism": "CD40 signaling promotes immune activation and joint inflammation.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may regulate ICOSLG surface expression and immune synapse formation.", "mechanism": "ICOSLG-ICOS interaction drives T cell activation and autoimmunity.", "protein": "ICOSLG", "protein_enriched": { "function": "Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion (PubMed:11007762, PubMed:11023515, PubMed:30498080). Also indu", "gene_name": "ICOSLG", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G37773JL", "G48414YA", "G80920RR", "G22768VO", "G11115RO", "G53046BR", "G60743GT", "G81375TC", "G87139BK", "G49108TO", "G47518TP", "G61256FT" ], "uniprot_id": "O75144" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation of FCGR3A modulates IgG binding affinity and effector function.", "mechanism": "FCGR3A mediates immune complex clearance and antibody-dependent cytotoxicity.", "protein": "FCGR3A", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect FCRL3 receptor function and cell surface localization.", "mechanism": "FCRL3 regulates B cell tolerance; upregulation disrupts immune homeostasis.", "protein": "FCRL3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may influence PADI4 stability or localization.", "mechanism": "PADI4 catalyzes citrullination, generating autoantigens in RA.", "protein": "PADI4", "protein_enriched": { "function": "Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance (PubMed:15339660, PubMed:", "gene_name": "PADI4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM07" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect ALDH2 antigenicity and immune recognition.", "mechanism": "ALDH2 is implicated as a citrullinated antigen and may contribute to autoimmunity.", "protein": "ALDH2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12383807" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "As an ECM glycoprotein, glycosylation may affect its structural role.", "mechanism": "HAPLN4 links CNS function and systemic autoimmunity; mechanism unclear.", "protein": "HAPLN4", "protein_enriched": { "function": "Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endop", "gene_name": "MIA2", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G62765YT", "G31852PQ" ], "uniprot_id": "Q96PC5" }, "relationship_type": "causal", "source_pmcid": "PMC12383807" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may modulate SUGP1 nuclear function.", "mechanism": "SUGP1 regulates cholesterol metabolism, linking lipid homeostasis to RA risk.", "protein": "SUGP1", "protein_enriched": { "function": "Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways incl", "gene_name": "MOB4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3A3" }, "relationship_type": "causal", "source_pmcid": "PMC12383807" }, { "confidence": "high", "disease": "Skin aging", "glycan_involvement": "Reduced glycosylation impairs collagen stability and assembly.", "mechanism": "Decreased synthesis and altered glycosylation reduce ECM integrity and elasticity.", "protein": "Collagen (Type I, III, IV, VII)", "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Impaired wound healing", "glycan_involvement": "Glycosylation affects fibronectin's ECM binding and cell interactions.", "mechanism": "Reduced fibronectin impairs cell adhesion and migration during repair.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Skin aging", "glycan_involvement": "Glycosylation critical for laminin's structural and signaling roles.", "mechanism": "Reduced laminin disrupts basement membrane and epidermal-dermal cohesion.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "high", "disease": "Photoaging", "glycan_involvement": "AGE-mediated glycation stiffens elastin, reducing function.", "mechanism": "Fragmentation and cross-linking of elastin fibers lead to loss of elasticity.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "high", "disease": "Wrinkle formation", "glycan_involvement": "Some MMPs are glycoproteins; glycosylation may affect secretion/activity.", "mechanism": "Upregulated MMPs degrade collagen and elastin, promoting wrinkles.", "protein": "Matrix Metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-12)", "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Skin aging", "glycan_involvement": "Glycosylation modulates TIMP stability and MMP binding.", "mechanism": "TIMPs inhibit MMPs, preserving ECM; decreased TIMPs accelerate aging.", "protein": "Tissue Inhibitors of Metalloproteinases (TIMP-1, TIMP-2)", "relationship_type": "protective", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosaminoglycan chains essential for function.", "mechanism": "Decorin binds collagen, regulates fibrillogenesis, and inhibits fibrosis.", "protein": "Decorin", "relationship_type": "protective", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosaminoglycan chains mediate receptor interactions.", "mechanism": "Biglycan activates TLRs, promoting inflammation.", "protein": "Biglycan", "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "medium", "disease": "Scarring", "glycan_involvement": "Chondroitin sulfate chains modulate cell-ECM interactions.", "mechanism": "Versican accumulation promotes cell migration and scar formation.", "protein": "Versican", "protein_enriched": { "function": "May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "high", "disease": "Skin dryness", "glycan_involvement": "Directly responsible for GAG (HA) synthesis.", "mechanism": "Reduced HAS expression lowers hyaluronic acid, decreasing hydration.", "protein": "Hyaluronic Acid Synthases (HAS1, HAS2, HAS3)", "relationship_type": "causal", "source_pmcid": "PMC12383820" }, { "confidence": "high", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Efflux transporter limits drug penetration into brain, reducing efficacy of anti-T. gondii drugs.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383829" }, { "confidence": "high", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation affects trafficking and activity.", "mechanism": "Efflux transporter restricts brain access of drugs like spiramycin.", "protein": "Multidrug-resistant protein 2 (Mrp2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383829" }, { "confidence": "medium", "disease": "Toxoplasmosis", "glycan_involvement": "Surface glycosylation mediates host-parasite interactions.", "mechanism": "Upregulated in drug-adapted T. gondii, contributing to transient drug tolerance.", "protein": "Tachyzoite membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12383829" }, { "confidence": "medium", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Increased IFN-\u03b3 production correlates with improved survival in T. gondii-infected mice treated with TSCs.", "protein": "IFN-\u03b3", "relationship_type": "protective", "source_pmcid": "PMC12383829" }, { "confidence": "medium", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation essential for bioactivity.", "mechanism": "Elevated IL-12 enhances immune response against T. gondii.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12383829" }, { "confidence": "medium", "disease": "Toxoplasmosis", "glycan_involvement": "Some ribosomal proteins are glycosylated, affecting assembly.", "mechanism": "C3 and C4 bind ribosomal proteins, interfering with parasite protein synthesis.", "protein": "Ribosomal proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383829" }, { "confidence": "medium", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation modulates parasite attachment.", "mechanism": "Host cell glycoproteins mediate T. gondii entry and survival.", "protein": "Human foreskin fibroblast surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383829" }, { "confidence": "low", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation required for antigen presentation.", "mechanism": "CD1-restricted T cells may contribute to anti-T. gondii immunity.", "protein": "CD1", "protein_enriched": { "function": "Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells", "gene_name": "Cd1d2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P11610" }, "relationship_type": "protective", "source_pmcid": "PMC12383829" }, { "confidence": "low", "disease": "Toxoplasmosis", "glycan_involvement": "Recognizes mannose-rich glycoproteins.", "mechanism": "Used to stimulate T cell proliferation in immunological assays.", "protein": "Concanavalin A receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12383829" }, { "confidence": "low", "disease": "Toxoplasmosis", "glycan_involvement": "Glycosylation modulates ligand recognition.", "mechanism": "Used to stimulate B cell proliferation in immunological assays.", "protein": "Lipopolysaccharide receptor (TLR4)", "relationship_type": "biomarker", "source_pmcid": "PMC12383829" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "A\u03b2PP is a glycoprotein; glycosylation affects aggregation and clearance.", "mechanism": "Abnormal metabolism and aggregation of A\u03b2PP leads to amyloid plaque formation.", "protein": "Amyloid \u03b2 precursor protein (A\u03b2PP)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Ovalbumin is a glycoprotein; immune response may be influenced by glycan structures.", "mechanism": "Increased anti-egg albumin antibodies in serum and CSF of AD patients, especially severe cases.", "protein": "Ovalbumin (egg albumin)", "protein_enriched": { "function": "Non-inhibitory serpin. Storage protein of egg white", "gene_name": "SERPINB14", "glycan_count": 71, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G05724UK", "G06110VR", "G20425TQ", "G23432EQ", "G23453IV", "G33609NS", "G39188ZX", "G50045TK", "G60145BJ", "G79568CQ", "G81295CK", "G00951UF", "G04607LO", "G08076GP", "G08520NM", "G10133VD", "G10562QT", "G12586PN", "G14260UH", "G14669DU", "G16828VN", "G17441OD", "G20966TZ", "G22573RC", "G22768VO", "G26759AS", "G26798CI", "G31936TA", "G32550BI", "G33279YE", "G34442SS", "G34527RW", "G35619UY", "G39213VZ", "G39619TI", "G42039DE", "G45882FV", "G47011KD", "G48584BU", "G49108TO", "G49889OJ", "G52187WF", "G55220VL", "G56748EO", "G57611UV", "G57671LP", "G59471TH", "G59942FB", "G61278VW", "G63628AV", "G65540UB", "G66538GV", "G66766XF", "G67093QB", "G71838YU", "G72398FA", "G72735IY", "G74916CC", "G76329HL", "G76807JB", "G79198BK", "G80966KZ", "G83161QT", "G84838NP", "G85737WG", "G86408JD", "G93500PH", "G94106MV", "G94506PU", "G94626GC", "G98140IX" ], "uniprot_id": "P01012" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may affect serpin stability and function.", "mechanism": "Serpin A3 is upregulated in AD and may promote amyloid plaque formation.", "protein": "Serpin A3 (\u03b11-antichymotrypsin)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may modulate neuroserpin activity.", "mechanism": "Neuroserpin regulates protease activity in CNS; dysregulation implicated in AD.", "protein": "Serpin I1 (neuroserpin)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may affect secretion and function.", "mechanism": "Serpin B1 protects cells during inflammation and maintains barrier integrity; impairment may contribute to AD.", "protein": "Serpin B1", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may influence protein stability and activity.", "mechanism": "Angiotensinogen regulates cerebral blood flow and BBB permeability; lower levels in AD.", "protein": "Serpin A8 (angiotensinogen)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Neu5Gc is a non-human sialic acid; its presence in glycoproteins is immunogenic.", "mechanism": "Neu5Gc incorporation into human glycoproteins triggers immune response.", "protein": "N-Glycolyl-Neuraminic acid (Neu5Gc)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects serpin A1 function.", "mechanism": "Serpin A1 upregulation observed in AD; may be neuroprotective or pathogenic.", "protein": "Serpin A1 (\u03b11-antitrypsin)", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "Serpin E1 involved in CNS protease regulation; altered levels in AD.", "protein": "Serpin E1", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may affect function.", "mechanism": "Serpin F1 implicated in CNS events in AD.", "protein": "Serpin F1", "relationship_type": "causal", "source_pmcid": "PMC12383860" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of iridoids (glucose moiety) enables GLUT-1 transport", "mechanism": "GLUT-1 may mediate CNS entry of glycosylated neuroprotective iridoids (GP, ASP)", "protein": "GLUT-1 (Glucose transporter 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation (glucose) is essential for transporter recognition", "mechanism": "GLUT-1 may facilitate brain delivery of glycosylated neuroprotective compounds", "protein": "GLUT-1 (Glucose transporter 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AChE is a glycoprotein; glycosylation affects stability and function", "mechanism": "AChE inhibition by GP/ASP improves cholinergic neurotransmission", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BChE is a glycoprotein; glycosylation modulates activity", "mechanism": "BChE inhibition by GP/ASP may enhance cholinergic signaling", "protein": "Butyrylcholinesterase (BChE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "AChE glycosylation influences CNS localization", "mechanism": "AChE inhibition may support cholinergic function in PD", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "P-gp is a glycoprotein; glycosylation affects transporter function", "mechanism": "P-gp efflux limits CNS drug entry; GP/ASP are predicted substrates", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12384043" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "Drug glycosylation (glucose) is required for GLUT-1 recognition", "mechanism": "GLUT-1-mediated transport of glycosylated drugs may improve CNS delivery", "protein": "GLUT-1 (Glucose transporter 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "AChE glycosylation modulates enzyme activity", "mechanism": "AChE inhibition may reduce neuronal damage post-stroke", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "BChE glycosylation affects CNS function", "mechanism": "BChE inhibition may support cholinergic tone in PD", "protein": "Butyrylcholinesterase (BChE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384043" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "P-gp glycosylation is critical for transporter activity", "mechanism": "P-gp efflux may restrict CNS access of neuroprotective glycosides", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12384043" }, { "confidence": "medium", "disease": "Uveal melanoma metastasis", "glycan_involvement": "Not directly discussed; BAP-1 is a glycoprotein but glycosylation not specified.", "mechanism": "Loss of BAP-1 (often via monosomy 3) is associated with increased risk of metastasis in uveal melanoma.", "protein": "BAP-1", "protein_enriched": { "function": "Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity (By s", "gene_name": "DTX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86Y01" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384185" }, { "confidence": "high", "disease": "Proteinuria (in non-CAKUT pediatric CKD)", "glycan_involvement": "TSP-1 is a heavily glycosylated protein; glycosylation may affect its stability and interactions.", "mechanism": "Lower plasma TSP-1 levels are associated with increased risk of proteinuria events, possibly reflecting glomerular barrier injury and urinary loss.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Nephrotic Syndrome (pediatric, non-CAKUT)", "glycan_involvement": "Glycosylation may influence TSP-1's filtration and loss in urine.", "mechanism": "Lower plasma TSP-1 correlates with higher proteinuria and risk of relapse/progression.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Focal Segmental Glomerulosclerosis (FSGS)", "glycan_involvement": "Glycosylation affects TSP-1's interactions with TGF-\u03b2 and ECM.", "mechanism": "In adults, higher plasma TSP-1 correlates with proteinuria severity and CKD progression.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation modulates TSP-1's TGF-\u03b2 activation.", "mechanism": "TSP-1 activates TGF-\u03b2, promoting renal fibrosis and proteinuria.", "protein": "Thrombospondin-1", "relationship_type": "causal", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Pediatric Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation may affect TSP-1's plasma stability and renal deposition.", "mechanism": "Lower plasma TSP-1 may indicate severe glomerular injury and risk of progression.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "low", "disease": "CAKUT", "glycan_involvement": "Glycosylation status not directly linked to CAKUT pathology.", "mechanism": "Plasma TSP-1 levels are not associated with proteinuria events; may reflect metabolic/nutritional status.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Renal Fibrosis", "glycan_involvement": "Glycosylation critical for TSP-1 structure and function.", "mechanism": "TSP-1 activates TGF-\u03b2, driving fibrosis; inhibition reduces fibrosis in models.", "protein": "Thrombospondin-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Proteinuria (adult CKD)", "glycan_involvement": "Glycosylation may affect disease-specific TSP-1 behavior.", "mechanism": "Higher plasma TSP-1 correlates with proteinuria and CKD progression in adults (opposite to pediatric findings).", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12384188" }, { "confidence": "low", "disease": "Glomerular Injury", "glycan_involvement": "Glycosylation may modulate protective functions.", "mechanism": "TSP-1 may stabilize vascular integrity and limit inflammation; lower levels may reflect loss of protection.", "protein": "Thrombospondin-1", "relationship_type": "protective", "source_pmcid": "PMC12384188" }, { "confidence": "medium", "disease": "Renal Disease (general)", "glycan_involvement": "Glycosylation may influence drug targeting and efficacy.", "mechanism": "TSP-1 inhibitors are in development for renal fibrosis and proteinuria.", "protein": "Thrombospondin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384188" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at N331/N343 shields epitopes, aiding immune evasion.", "mechanism": "RBD mediates viral entry via ACE2 binding, initiating infection.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "High-mannose and phosphomannose N-glycans enhance alum adsorption and immunogenicity.", "mechanism": "Used as a vaccine antigen, induces strong neutralizing antibody responses.", "protein": "H-MAN/RBD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Complex N-glycans (fucosylated/sialylated) lack phosphomannose, reducing alum adsorption and immunogenicity.", "mechanism": "Used as a vaccine antigen, but induces lower antibody titers than H-MAN/RBD.", "protein": "Complex/RBD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Phosphomannose N-glycans enhance alum adsorption and immune response.", "mechanism": "Vaccine antigen with low-mannose but high phosphomannose, induces high antibody titers.", "protein": "L-MAN/RBD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Reduced phosphomannose leads to poor alum adsorption and weak immunogenicity.", "mechanism": "Vaccine antigen with low-mannose and low phosphomannose, induces low antibody titers.", "protein": "L-MAN-P/RBD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "N-glycosylation masks epitopes, facilitating immune evasion.", "mechanism": "RBD is essential for viral attachment and entry into host cells.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Phosphomannose modification increases negative charge, promoting alum binding and immune activation.", "mechanism": "Immunization with H-MAN/RBD elicits high neutralizing antibody titers, conferring protection.", "protein": "H-MAN/RBD", "relationship_type": "protective", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Lacks phosphomannose, resulting in lower alum adsorption and immunogenicity.", "mechanism": "Immunization induces antibodies, but less effective than H-MAN/L-MAN RBD.", "protein": "Complex/RBD", "relationship_type": "protective", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Phosphomannose enhances alum adsorption and immunogenicity.", "mechanism": "Immunization elicits strong antibody responses, similar to H-MAN/RBD.", "protein": "L-MAN/RBD", "relationship_type": "protective", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Low phosphomannose reduces alum adsorption and immune response.", "mechanism": "Immunization elicits weak antibody responses, less protective.", "protein": "L-MAN-P/RBD", "relationship_type": "protective", "source_pmcid": "PMC12384197" }, { "confidence": "high", "disease": "Infectious diseases", "glycan_involvement": "Glycosylation stabilizes structure and receptor interactions.", "mechanism": "Broad-spectrum antimicrobial activity via iron sequestration, membrane disruption, and inhibition of microbial adhesion.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", 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inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", 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"G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384211" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation facilitates transport and stability.", "mechanism": "Lf crosses blood-brain barrier, reduces oxidative stress and inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", 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"G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384211" }, { "confidence": "high", "disease": "Respiratory infections", "glycan_involvement": "Glycosylation supports mucosal stability and 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"Colorectal polyps/cancer", "glycan_involvement": "Glycosylation affects stability and bioactivity.", "mechanism": "Lf inhibits polyp growth and may prevent colorectal cancer.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", 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"G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12384211" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Glycosylation required for receptor-mediated iron delivery.", "mechanism": "Lf supplementation increases hemoglobin and serum iron, reduces inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions 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"G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384211" }, { "confidence": "medium", "disease": "Hyperoxia-induced tissue injury", "glycan_involvement": "Glycosylation stabilizes antioxidant function.", "mechanism": "Lf reduces oxidative stress and tissue damage.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12384211" }, { "confidence": "high", "disease": "Cholecystitis", "glycan_involvement": "CRP glycosylation affects its stability and inflammatory signaling.", "mechanism": "CRP elevation indicates acute inflammation in cholecystitis and predicts postoperative complications.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "high", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation modulates GGT activity and secretion.", "mechanism": "Elevated GGT reflects biliary obstruction due to stones.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "medium", "disease": "Cholecystitis", "glycan_involvement": "Glycosylation influences ALT serum half-life.", "mechanism": "ALT elevation signals hepatocellular injury secondary to gallbladder inflammation.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "medium", "disease": "Cholecystitis", "glycan_involvement": "Glycosylation affects AST stability.", "mechanism": "AST elevation is associated with liver involvement in gallbladder disease.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation regulates amylase secretion.", "mechanism": "Serum amylase increases in gallstone-induced pancreatitis.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation affects lipase activity.", "mechanism": "Lipase elevation is diagnostic for pancreatitis secondary to gallstones.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory role.", "mechanism": "CRP is elevated in systemic inflammation during pancreatitis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "medium", "disease": "Choledocholithiasis", "glycan_involvement": "Glycosylation impacts CRP's immune interactions.", "mechanism": "CRP elevation reflects acute biliary inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "medium", "disease": "Obesity-associated gallbladder disease", "glycan_involvement": "Altered glycosylation in obesity may affect GGT function.", "mechanism": "Obesity increases GGT, indicating higher risk of gallbladder complications.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "medium", "disease": "Hemolytic disorders (e.g., thalassemia, hereditary spherocytosis)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory response.", "mechanism": "CRP used to monitor inflammation in hemolysis-related gallstone formation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12384218" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding and signaling.", "mechanism": "Promotes cell adhesion, migration, EMT, and therapy resistance via interaction with hyaluronic acid and Id1/Id3 induction.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12384346" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation critical for epitope recognition and function.", "mechanism": "Associated with stemness, tumorigenicity, metastasis, and resistance to therapy via PI3K/AKT pathway activation.", "protein": "CD133", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384346" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Heavily glycosylated; sialylation affects cell adhesion and immune evasion.", "mechanism": "Identifies a subpopulation with enhanced stem-like properties, migration, and drug resistance.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384346" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Marks cells with high tumorigenicity and metastatic potential; involved in stemness and plasticity.", "protein": "CD271 (NGFR)", "protein_enriched": { "function": "Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lowe", "gene_name": "NGFR", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G37891WT", "G74722FL", "G78768PN", "G81006GJ" ], "uniprot_id": "P08138" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384346" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect trafficking and stability.", "mechanism": "Mediates chemoresistance and radioresistance via drug efflux and NFkB pathway activation; marks therapy-resistant CSCs.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12384346" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Putative glycosylation; not detailed.", "mechanism": "Marks CSCs with high tumorigenicity and radioresistance; targeting reduces tumorigenesis.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384346" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Enriched in CSCs; anti-CD20 therapy (rituximab) led to remission in refractory melanoma.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384346" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "N-glycosylation critical for stability and immune recognition.", "mechanism": "Immune checkpoint; upregulated in CSCs for immune evasion; targeted by ICIs.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384346" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects surface expression.", "mechanism": "Marks CSCs with drug efflux capacity and radioresistance.", "protein": "ABCG2", "relationship_type": "biomarker", "source_pmcid": "PMC12384346" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Ganglioside (glycolipid); sialylation essential for function.", "mechanism": "CSC marker; associated with tumorigenicity, metastasis, and therapy resistance; target for CAR-T and bsAb therapies.", "protein": "GD2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384346" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Azacitidine is a nucleoside analog that incorporates into RNA and DNA, affecting epigenetic regulation, but is not a glycoprotein nor directly modifies glycosylation.", "mechanism": "Azacitidine is used as a maintenance therapy to prolong remission and improve survival in AML patients unfit for intensive chemotherapy.", "protein": "Azacitidine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384391" }, { "confidence": "high", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "No direct glycan involvement; acts via DNA methylation inhibition.", "mechanism": "Azacitidine is approved for treatment of MDS and secondary AML, improving survival and delaying progression.", "protein": "Azacitidine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384391" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "N-glycosylation branching", "mechanism": "Promotes increased N-glycan branching, enhancing growth factor signaling and metastatic potential.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384407" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Core fucosylation of N-glycans", "mechanism": "Downregulation enhances metastasis via upregulation of L1CAM; may have tumor-suppressive role.", "protein": "FUT8", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12384407" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "N-glycosylation modulates cell adhesion", "mechanism": "Upregulated when FUT8 is downregulated, promoting metastasis.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12384407" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Recognition of O-glycosylation (Tn/STn antigens)", "mechanism": "Binds Tn and sialyl-Tn antigens; expressed in ~26% of OS samples, enabling targeted immunotherapy.", "protein": "CD301 (CLEC10A/MGL)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384407" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "O-glycosylation (Tn/STn antigens)", "mechanism": "Truncated O-glycans facilitate detachment, immune evasion, and metastasis.", "protein": "Mucins (Tn/STn antigens)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12384407" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation modulates immune recognition", "mechanism": "Upregulated in cancer stem cells and immune evasion ('don't-eat-me' signal).", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384407" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation affects stability and immune interactions", "mechanism": "Overexpression leads to immune suppression; target for checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12384407" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Ganglioside glycan structure", "mechanism": "Targeted by CAR-NK/CAR-T therapies for tumor cell killing.", "protein": "GD2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384407" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation modulates immune checkpoint function", "mechanism": "Targeted by CAR-NK/CAR-T therapies; associated with immune evasion.", "protein": "B7-H3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384407" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation affects receptor function", "mechanism": "Overexpression correlates with poor outcome and metastasis.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384407" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "EpCAM is a transmembrane glycoprotein; glycosylation affects its stability and function.", "mechanism": "EpCAM is overexpressed in breast cancer and associated with poor prognosis; regulates cell proliferation, adhesion, and migration.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384426" }, { "confidence": "high", "disease": "Metastatic breast cancer", "glycan_involvement": "Glycosylation modulates EpCAM-mediated cell adhesion and clustering.", "mechanism": "EpCAM+ CTCs predict cluster presence and size, facilitating CTC clustering and metastasis.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "high", "disease": "Metastatic breast cancer", "glycan_involvement": "Trop2 is a glycoprotein; glycosylation influences its adhesive and signaling properties.", "mechanism": "Trop2+ CTCs are associated with cluster formation and metastatic competency, especially in aggressive subtypes.", "protein": "Trop2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "Tacstd2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q8BGV3" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Brain metastasis (from breast cancer)", "glycan_involvement": "Glycosylation may regulate EpCAM-mediated adhesion in CTC clusters.", "mechanism": "Increase in EpCAM+ CTC clusters after brain metastasis diagnosis, especially in HER2+ cancers.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Bone metastasis (from breast cancer)", "glycan_involvement": "Glycosylation may affect Trop2's role in CTC adhesion and dissemination.", "mechanism": "Continued shedding of Trop2+ CTCs is a feature of bone metastatic disease.", "protein": "Trop2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "Tacstd2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q8BGV3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "high", "disease": "Metastatic breast cancer", "glycan_involvement": "CD45 is a heavily glycosylated protein; glycosylation affects immune cell interactions.", "mechanism": "Presence of CD45+ cells in CTC clusters predicts larger cluster size and is associated with increased metastatic potential.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Lung metastasis (from breast cancer)", "glycan_involvement": "Glycosylation may modulate EpCAM's adhesive properties in CTC clusters.", "mechanism": "EpCAM+ CTC clusters increase after lung metastasis diagnosis.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Brain metastasis (from breast cancer)", "glycan_involvement": "Glycosylation may influence Trop2-mediated homotypic adhesion.", "mechanism": "Larger Trop2+ CTC clusters correspond to brain metastasis, especially in HER2+ disease.", "protein": "Trop2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "Tacstd2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q8BGV3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "CK19 is a glycoprotein; glycosylation may affect its role in cell adhesion.", "mechanism": "CK19 is expressed by breast cancer CTCs; overexpression in tumor tissue is linked to recurrence and cell adhesion.", "protein": "Cytokeratin 19", "relationship_type": "biomarker", "source_pmcid": "PMC12384426" }, { "confidence": "medium", "disease": "Metastatic breast cancer", "glycan_involvement": "Glycosylation may affect EpCAM's immunogenicity and therapeutic targeting.", "mechanism": "EpCAM is a target for CAR-T cell immunotherapy in solid tumors, including metastatic breast cancer.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384426" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein-associated disorder (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG glycoprotein trigger CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12384486" }, { "confidence": "medium", "disease": "Downbeat nystagmus (DBN)", "glycan_involvement": "Glycosylation of MOG may influence immune-mediated pathogenesis.", "mechanism": "MOGAD can present with DBN due to inflammatory lesions affecting vestibular/ocular motor pathways.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12384486" }, { "confidence": "medium", "disease": "Longitudinally extensive transverse myelitis (LETM)", "glycan_involvement": "Glycosylation may modulate MOG antigenicity and immune response.", "mechanism": "MOG autoimmunity leads to demyelinating lesions in the spinal cord.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12384486" }, { "confidence": "low", "disease": "Status epilepticus", "glycan_involvement": "Glycosylation may affect MOG's immunogenicity.", "mechanism": "MOGAD can involve the brain, leading to seizures/status epilepticus.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12384486" }, { "confidence": "high", "disease": "High-grade glioma (HGG)", "glycan_involvement": "B7-H3 is a glycoprotein; glycosylation likely affects stability and cell surface expression.", "mechanism": "Elevated B7-H3 expression distinguishes HGG from LGG; correlates with higher grade and poor prognosis.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "high", "disease": "High-grade glioma (HGG)", "glycan_involvement": "Glycosylation may influence antibody binding and immune recognition.", "mechanism": "Targeting B7-H3 with CAR-T cells or antibodies shows anti-tumor activity in preclinical models.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384666" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "Glycosylation status may affect detection by immunohistochemistry.", "mechanism": "Low B7-H3 expression is characteristic of LGG and predicts better prognosis.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may modulate B7-H3 function and immune evasion.", "mechanism": "B7-H3 is highly expressed in GBM and correlates with poor survival.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Diffuse intrinsic pontine glioma (DIPG)", "glycan_involvement": "Glycosylation may affect therapeutic antibody efficacy.", "mechanism": "B7-H3 is overexpressed in DIPG; targeted therapies are under investigation.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Atypical teratoid/rhabdoid tumor (ATRT)", "glycan_involvement": "Glycosylation may influence cell surface localization.", "mechanism": "All ATRT cases show strong B7-H3 expression.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Meningioma", "glycan_involvement": "Glycosylation may affect immunoreactivity.", "mechanism": "75\u2013100% of meningiomas are B7-H3-positive.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Medulloblastoma", "glycan_involvement": "Glycosylation may impact detection and function.", "mechanism": "Moderate-to-strong B7-H3 expression observed.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Ependymoma", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "B7-H3 is frequently upregulated.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Glycosylation may influence immune evasion.", "mechanism": "B7-H3 is overexpressed in neuroblastoma.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker", "source_pmcid": "PMC12384666" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Not specified in article.", "mechanism": "Serum ACBP/DBI levels are elevated in obese individuals; hepatic expression predicts weight loss response after bariatric surgery.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not specified in article.", "mechanism": "Higher baseline serum ACBP/DBI correlates with greater steatosis and fibrosis after bariatric surgery, indicating poorer histological improvement.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Not specified in article.", "mechanism": "Serum ACBP/DBI levels positively correlate with NAFLD Activity Score (NAS), reflecting hepatic inflammation and injury.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not specified in article.", "mechanism": "ACBP/DBI stimulates appetite via GABA A receptor signaling; genetic deletion prevents high-fat diet-induced weight gain in preclinical models.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "causal", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Not specified in article.", "mechanism": "High extracellular ACBP/DBI levels associated with cardiovascular disease.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "Anorexia Nervosa", "glycan_involvement": "Not specified in article.", "mechanism": "Serum ACBP/DBI levels are decreased in patients with anorexia nervosa.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not specified in article.", "mechanism": "Pharmacological inhibition of ACBP/DBI ameliorates liver injury in murine models.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384758" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Not specified in article.", "mechanism": "Lower hepatic ACBP/DBI expression at baseline predicts greater weight loss after bariatric surgery.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not specified in article.", "mechanism": "Extracellular ACBP/DBI inhibits autophagy, potentially contributing to metabolic inflammation and liver disease progression.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "causal", "source_pmcid": "PMC12384758" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not specified in article.", "mechanism": "Serum ACBP/DBI increases after bariatric surgery, possibly as a counter-regulatory mechanism to weight loss.", "protein": "Acyl-CoA Binding Protein (ACBP) / Diazepam-Binding Inhibitor (DBI)", "protein_enriched": { "function": "Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD)", "gene_name": "DBI", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384758" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-MOG antibodies are diagnostic for MOGAD and predict a favorable disease course in children.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is glycosylated; glycosylation may influence immune recognition and pathogenicity.", "mechanism": "Anti-AQP4 antibodies are diagnostic for NMOSD and predict poor prognosis and persistent disability.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Optic Neuritis", "glycan_involvement": "Glycosylation of MOG may modulate antibody binding and disease phenotype.", "mechanism": "MOG antibodies are frequently found in pediatric optic neuritis, especially bilateral cases.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Transverse Myelitis", "glycan_involvement": "Glycosylation may affect AQP4 antibody pathogenicity.", "mechanism": "AQP4 antibodies are associated with longitudinally extensive transverse myelitis in NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation state may influence MOG antigenicity.", "mechanism": "MOG antibodies are rarely present in pediatric MS; their absence helps differentiate MS from MOGAD.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation not directly implicated in MS pathogenesis.", "mechanism": "AQP4 antibodies are typically absent in MS, aiding differential diagnosis from NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Acute Disseminated Encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation may affect MOG antibody binding.", "mechanism": "MOG antibodies may be present in ADEM, especially in younger children, and predict monophasic course.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "Acute Disseminated Encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation not directly implicated.", "mechanism": "AQP4 antibodies are typically absent in ADEM, supporting differential diagnosis.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384780" }, { "confidence": "medium", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation may influence MOG immunogenicity and response to therapy.", "mechanism": "MOG is the target of pathogenic antibodies; immunotherapy directed at B cells (e.g., Rituximab) may be effective.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384780" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "Glycosylation may modulate AQP4 antibody binding and pathogenicity.", "mechanism": "AQP4 is the target of pathogenic antibodies; B cell depletion (e.g., Rituximab) reduces relapses and disability.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384780" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns can affect its diagnostic specificity.", "mechanism": "Elevated serum AFP is associated with HCC presence and progression.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation changes in AFP may reflect disease stage.", "mechanism": "AFP levels can increase with advanced fibrosis/cirrhosis, not only HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "high", "disease": "Chronic hepatitis B infection", "glycan_involvement": "HBsAg is a glycosylated viral envelope protein; glycosylation is essential for viral infectivity and immune evasion.", "mechanism": "HBsAg positivity indicates active HBV infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of HBsAg may modulate immune recognition and chronicity.", "mechanism": "Chronic HBV infection (HBsAg+) is a major risk factor for HCC development.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12384809" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "DCP is a glycoprotein; glycosylation may affect its serum levels and detection.", "mechanism": "Elevated DCP is associated with HCC and used for diagnosis.", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "low", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "Glycosylation may influence AFP's diagnostic accuracy.", "mechanism": "AFP can be elevated in some CCA cases, though less specific.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "low", "disease": "Benign liver lesions (e.g., FNH, SHC)", "glycan_involvement": "Glycosylation patterns may help distinguish benign from malignant sources.", "mechanism": "AFP can be mildly elevated in some benign lesions, limiting specificity.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation of HBsAg may affect persistence and fibrogenesis.", "mechanism": "Chronic HBV infection (HBsAg+) leads to fibrosis and cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12384809" }, { "confidence": "low", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation may influence DCP's serum stability.", "mechanism": "DCP may be elevated in advanced fibrosis/cirrhosis.", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "medium", "disease": "Metastatic carcinoma (MET)", "glycan_involvement": "Glycosylation status may help distinguish primary from metastatic lesions.", "mechanism": "AFP is usually not elevated in MET, aiding differential diagnosis.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12384809" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Overexpression leads to active efflux of chemotherapeutics, causing multidrug resistance.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects trafficking and function.", "mechanism": "Effluxes drugs (e.g., TKIs, topotecan), protects cancer stem cells, contributes to relapse and metastasis.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation stabilizes membrane localization.", "mechanism": "High expression correlates with oxaliplatin resistance by reducing intracellular drug accumulation.", "protein": "ABCC2 (MRP2)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compoun", "gene_name": "ABCC2", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G59324HL" ], "uniprot_id": "Q92887" }, "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation required for membrane targeting.", "mechanism": "Effluxes gemcitabine, conferring resistance; knockdown increases drug sensitivity.", "protein": "ABCC5 (MRP5)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolite", "gene_name": "ABCC5", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15440" }, "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Pancreatic, breast, ovarian, brain, lung cancers", "glycan_involvement": "Heavily glycosylated; glycan chains mediate ligand binding and cell adhesion.", "mechanism": "Overexpressed on cancer stem cells; targeted by hyaluronic acid-conjugated nanoparticles for drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384834" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation influences trafficking and efflux activity.", "mechanism": "Exports glutathione, maintains redox homeostasis, supports resistance to 5-fluorouracil.", "protein": "MRP1 (ABCC1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor stability.", "mechanism": "Overexpressed in glioblastoma; targeted by transferrin-conjugated nanoparticles for drug delivery.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects receptor dimerization and antibody binding.", "mechanism": "Targeted by trastuzumab-conjugated nanoparticles, enhancing cytotoxicity in HER2-positive cells.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation regulates surface expression and immune evasion.", "mechanism": "Targeted by aptamer- or antibody-conjugated nanoparticles to enhance immune response and drug delivery.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384834" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "N-glycosylation modulates receptor activation and drug binding.", "mechanism": "Mutations or overexpression lead to resistance to EGFR inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12384834" }, { "confidence": "high", "disease": "Deep-seated Staphylococcus aureus infection", "glycan_involvement": "Fibrinogen glycosylation affects its stability and function in coagulation and inflammation.", "mechanism": "Elevated fibrinogen reflects systemic inflammation and coagulation activation during deep tissue invasion.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "high", "disease": "Deep-seated Staphylococcus aureus infection", "glycan_involvement": "D-dimer is a glycosylated fragment of cross-linked fibrin; glycosylation may affect clearance.", "mechanism": "Elevated D-dimer indicates increased fibrin degradation due to thrombosis and inflammation in deep tissue infection.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates fibrinogen's interaction with platelets and clotting factors.", "mechanism": "High fibrinogen promotes clot formation, increasing risk of thrombosis in infection.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may influence D-dimer's immunoreactivity and plasma half-life.", "mechanism": "D-dimer is released during fibrinolysis, marking active clot breakdown.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation is essential for fibrinogen secretion and stability.", "mechanism": "Acute-phase response increases fibrinogen synthesis during inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Deep-seated Staphylococcus aureus infection", "glycan_involvement": "CRP is glycosylated, which affects its solubility and immune functions.", "mechanism": "CRP rises in response to severe infection and tissue invasion.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Septic pulmonary emboli", "glycan_involvement": "Glycosylation may affect fibrinogen's role in embolus formation.", "mechanism": "Elevated fibrinogen correlates with increased risk of embolic complications in S. aureus infection.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Septic pulmonary emboli", "glycan_involvement": "Glycosylation may influence D-dimer detection and clearance.", "mechanism": "High D-dimer reflects ongoing fibrinolysis in embolic events.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Pyomyositis", "glycan_involvement": "Glycosylation is required for fibrinogen's inflammatory functions.", "mechanism": "Increased fibrinogen is associated with muscle infection and inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "medium", "disease": "Osteomyelitis", "glycan_involvement": "Glycosylation supports fibrinogen's stability and immune interactions.", "mechanism": "Elevated fibrinogen indicates bone infection and systemic response.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385118" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "No direct evidence of glycosylation involvement for HMGCS2 in this context.", "mechanism": "HMGCS2 upregulation enhances ketogenesis, reducing hepatocyte senescence and liver injury in NASH (especially with T2DM).", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385132" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "No direct evidence of glycosylation involvement.", "mechanism": "Downregulation of HMGCS2 impairs ketogenesis, accelerating NAFLD progression, especially with T2DM.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "ICAM-1 is a glycoprotein; glycosylation is essential for its function and stability.", "mechanism": "ICAM-1 upregulation (as part of SASP) marks increased hepatic inflammation and senescence in NASH and NASH-T2DM.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "ICAM-2 is a glycoprotein; glycosylation is important for its cell adhesion properties.", "mechanism": "ICAM-2 upregulation (as part of SASP) is associated with hepatic inflammation and progression of NASH.", "protein": "ICAM-2", "relationship_type": "biomarker", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "IL-1\u03b2 is glycosylated, which may affect secretion and stability.", "mechanism": "IL-1\u03b2 is upregulated in NASH and NASH-T2DM, reflecting increased inflammation and senescence.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "IL-6 is glycosylated, which can modulate its receptor binding and activity.", "mechanism": "IL-6 is upregulated as part of the SASP in NASH and NASH-T2DM, indicating inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "TNF-\u03b1 is glycosylated, which may influence its secretion and bioactivity.", "mechanism": "TNF-\u03b1 is elevated in NASH and NASH-T2DM, reflecting increased hepatic inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "No direct evidence of glycosylation involvement.", "mechanism": "HMGCS2 downregulation (and impaired ketogenesis) is associated with progression to hepatic fibrosis in NAFLD/NASH-T2DM.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "No direct evidence of glycosylation involvement.", "mechanism": "Suppressed HMGCS2 expression and ketogenesis are linked to increased risk of cirrhosis in NAFLD/NASH-T2DM.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12385132" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct evidence of glycosylation involvement.", "mechanism": "Reduced HMGCS2 and impaired ketogenesis may contribute to progression from NASH/fibrosis to HCC.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12385132" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation required for proper membrane localization and function.", "mechanism": "Regulates MCT1/MCT4 lactate transport, promoting glycolytic metabolism and tumor growth.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385171" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects immune checkpoint function.", "mechanism": "Lactylation/de-lactylation modulates nuclear translocation and cholesterol metabolism, driving immune evasion and tumor growth.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Liver ischemia/reperfusion injury (IRI)", "glycan_involvement": "Glycosylation influences extracellular release and immune signaling.", "mechanism": "Lactylation promotes HMGB1 secretion from macrophages, exacerbating inflammation and injury.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation may affect protein stability and interaction.", "mechanism": "Lactylation at K33 disrupts caspase-11 interaction, increasing pyroptosis and worsening liver injury.", "protein": "NEDD4", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including ", "gene_name": "NEDD4L", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q96PU5" }, "relationship_type": "causal", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation required for cell surface expression and immune function.", "mechanism": "Expression on CD8+ T cells correlates with improved immunotherapy response and prognosis.", "protein": "JAML", "protein_enriched": { "function": "Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. Th", "gene_name": "VPS36", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86VN1" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Liver angiogenesis", "glycan_involvement": "Glycosylation affects secretion and pro-angiogenic activity.", "mechanism": "Activated by histone lactylation and c-Myc, promotes angiogenesis in HCC.", "protein": "GP73 (GOLPH2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates membrane association and signaling.", "mechanism": "Lactylation enhances TGF-beta signaling, stabilizing Tregs and promoting immune evasion.", "protein": "MOESIN", "relationship_type": "causal", "source_pmcid": "PMC12385171" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect RNA binding and stability.", "mechanism": "Lactylation stabilizes mRNAs for serine metabolism and antioxidant defense, contributing to therapy resistance.", "protein": "IGF2BP3", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9NZI8" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may regulate vesicle sorting and protein interactions.", "mechanism": "Lactylation induces phase separation and sEV release, activating HSCs and promoting fibrosis.", "protein": "SORBS3", "protein_enriched": { "function": "Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesi", "gene_name": "SORBS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BX66" }, "relationship_type": "causal", "source_pmcid": "PMC12385171" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Glycosylation modulates receptor interaction and signaling.", "mechanism": "Lactylation increases IRS1 stability and activity, enhancing downstream signaling for proliferation and metastasis.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC12385171" }, { "confidence": "high", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "CD20 is a glycosylated membrane protein; glycosylation affects its stability and cell surface expression.", "mechanism": "CD20+ B cells predominate in hepatic MALT lymphoma infiltrates, aiding diagnosis.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "CD3 glycosylation modulates T cell receptor signaling.", "mechanism": "CD3 marks T cells, which are less prevalent in MALT lymphoma compared to B cells.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "CD5 glycosylation influences cell adhesion and signaling.", "mechanism": "CD5 negativity helps distinguish MALT lymphoma from other B-cell lymphomas.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "CD10 glycosylation affects protease activity and cell migration.", "mechanism": "CD10 negativity supports MALT lymphoma diagnosis over follicular lymphoma.", "protein": "CD10", "protein_enriched": { "function": "Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhi", "gene_name": "CD72", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX" ], "uniprot_id": "P21854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "BCL6 glycosylation may regulate nuclear localization and transcriptional repression.", "mechanism": "Focal BCL6 expression indicates follicular colonization by lymphoma cells.", "protein": "BCL6", "protein_enriched": { "function": "Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.", "gene_name": "BCL6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41182" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "CD23 glycosylation modulates IgE binding and immune regulation.", "mechanism": "CD23 focal colonization of follicles by B cells is characteristic of MALT lymphoma.", "protein": "CD23", "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Intrahepatic cholangiocarcinoma", "glycan_involvement": "CEA is heavily glycosylated; glycan structures affect its serum detectability.", "mechanism": "CEA is elevated in cholangiocarcinoma, used for differential diagnosis.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "high", "disease": "Intrahepatic cholangiocarcinoma", "glycan_involvement": "CA 19-9 is a glycan antigen (sialyl-Lewis a) on mucins and glycoproteins.", "mechanism": "CA 19-9 is a sialylated glycan epitope elevated in cholangiocarcinoma.", "protein": "CA 19-9", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:17502375, PubMed:22932902). Mediates transport of beta-alanine (PubMed:17502375). Can also mediate transport", "gene_name": "SLC6A13", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NSD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "Ki67 glycosylation may affect nuclear localization and cell cycle regulation.", "mechanism": "Ki67 proliferation index (~15%) indicates low-grade lymphoma.", "protein": "Ki67", "protein_enriched": { "function": "Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:3287", "gene_name": "MKI67", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P46013" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "medium", "disease": "Primary hepatic MALT lymphoma", "glycan_involvement": "Cyclin D1 glycosylation can regulate protein stability and cell cycle progression.", "mechanism": "Cyclin D1 negativity helps exclude mantle cell lymphoma.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385175" }, { "confidence": "high", "disease": "Bitterness perception (not a disease, but a sensory phenotype)", "glycan_involvement": "Glycosylation of salivary proteins mediates binding to phenolics.", "mechanism": "Phenolic compounds interact with salivary glycoproteins, altering taste perception.", "protein": "Salivary glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12385191" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Phenolics may affect glycoprotein interactions involved in cell adhesion and signaling.", "mechanism": "Phenolic compounds (e.g., ellagic acid, gallic acid, flavonoids) from fruits may modulate glycoprotein-mediated cell signaling, reducing cancer risk.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Potential modulation of glycoprotein-mediated metabolic pathways.", "mechanism": "Ellagic acid inhibits development of cancer cells and mitigates metabolic complications related to obesity.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Possible modulation of glycoprotein function in vascular endothelium.", "mechanism": "Flavonoids and phenolic acids from fruits reduce risk of cardiovascular disease via antioxidant effects.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Neurodegenerative diseases (e.g., Alzheimer's disease)", "glycan_involvement": "Glycosylation may affect neuroinflammatory signaling.", "mechanism": "Fruit phenolics may exert neuroprotective effects, possibly via glycoprotein-mediated pathways.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation status may influence insulin receptor function.", "mechanism": "Antioxidant phenolics may reduce diabetes risk by modulating glycoprotein-mediated glucose metabolism.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycoprotein interactions in vascular tissue may be modulated.", "mechanism": "Phenolic compounds reduce oxidative stress, lowering atherosclerosis risk.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Possible involvement of glycoprotein-mediated endothelial function.", "mechanism": "Antioxidant phenolics may lower stroke risk via vascular protection.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Cataracts", "glycan_involvement": "Glycoprotein oxidation may be reduced.", "mechanism": "Antioxidant phenolics may protect against cataract formation.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "low", "disease": "Lung disorders", "glycan_involvement": "Glycoprotein-mediated immune responses may be modulated.", "mechanism": "Fruit phenolics may reduce risk of lung disorders via antioxidant and anti-inflammatory effects.", "protein": "Salivary glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12385191" }, { "confidence": "high", "disease": "PFIC3", "glycan_involvement": "ABCB4 is glycosylated; glycosylation affects membrane localization and function.", "mechanism": "ABCB4 mutations impair phosphatidylcholine transport in bile, causing cholestasis.", "protein": "ABCB4", "protein_enriched": { "function": "Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the", "gene_name": "ABCB4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21439" }, "relationship_type": "causal", "source_pmcid": "PMC12385362" }, { "confidence": "medium", "disease": "Idiopathic Cholestasis", "glycan_involvement": "VPS33B glycosylation may regulate trafficking of glycoproteins in hepatocytes.", "mechanism": "VPS33B variants disrupt vesicular trafficking, affecting bile secretion.", "protein": "VPS33B", "protein_enriched": { "function": "May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Required for proper trafficking and targeting of", "gene_name": "VPS33B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H267" }, "relationship_type": "causal (possible)", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Aceruloplasminemia", "glycan_involvement": "CP is heavily glycosylated; glycosylation is essential for secretion and stability.", "mechanism": "CP mutations reduce ferroxidase activity, leading to iron overload and liver damage.", "protein": "CP (ceruloplasmin)", "relationship_type": "causal", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Hypobetalipoproteinemia", "glycan_involvement": "APOB glycosylation affects lipoprotein secretion and stability.", "mechanism": "APOB variants impair lipoprotein assembly, causing fatty liver and hypocholesterolemia.", "protein": "APOB", "relationship_type": "causal", "source_pmcid": "PMC12385362" }, { "confidence": "medium", "disease": "Congenital Glycosylation Disorder (CGD)", "glycan_involvement": "TMEM199 is involved in glycosyltransferase trafficking; defects cause global glycoprotein hypoglycosylation.", "mechanism": "TMEM199 deficiency disrupts Golgi homeostasis, leading to abnormal glycosylation and hepatic steatosis.", "protein": "TMEM199", "relationship_type": "causal (possible)", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Abetalipoproteinemia", "glycan_involvement": "MTTP glycosylation may affect lipid transfer activity.", "mechanism": "MTTP mutations impair lipid transfer, causing defective VLDL/LDL secretion and liver fibrosis.", "protein": "MTTP", "protein_enriched": { "function": "Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:15897609, PubMed:16478722, PubMed:22236406, PubMed:23475612, PubMed:25108285, PubMed:", "gene_name": "MTTP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55157" }, "relationship_type": "causal", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Glycogen Storage Disease Type IIIa", "glycan_involvement": "AGL is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "AGL deficiency impairs glycogen debranching, leading to hepatic and muscular glycogen accumulation.", "protein": "AGL", "protein_enriched": { "function": "Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation", "gene_name": "AGL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35573" }, "relationship_type": "causal", "source_pmcid": "PMC12385362" }, { "confidence": "medium", "disease": "Severe Congenital Liver Disease (FOCAD-related)", "glycan_involvement": "FOCAD glycosylation may regulate cell adhesion and signaling in liver.", "mechanism": "FOCAD mutations cause progressive hepatic dysfunction and cirrhosis.", "protein": "FOCAD", "protein_enriched": { "function": "", "gene_name": "C22orf23", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZE7" }, "relationship_type": "causal (possible)", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Idiopathic Cholestasis", "glycan_involvement": "Glycosylation modulates ABCB4 function and disease severity.", "mechanism": "Heterozygous ABCB4 variants predispose to milder cholestatic disease, cholelithiasis, and pregnancy-related cholestasis.", "protein": "ABCB4", "protein_enriched": { "function": "Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the", "gene_name": "ABCB4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21439" }, "relationship_type": "causal (heterozygous effect)", "source_pmcid": "PMC12385362" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "Altered glycosylation may affect CP stability and iron metabolism.", "mechanism": "CP variants are linked to hyperferritinemia, hepatic iron overload, and advanced fibrosis in MASLD.", "protein": "CP (ceruloplasmin)", "relationship_type": "biomarker", "source_pmcid": "PMC12385362" }, { "confidence": "high", "disease": "Peritoneal Tuberculosis (PTB)", "glycan_involvement": "Mucin-type O-glycosylation critical for secretion and immune recognition.", "mechanism": "Elevated due to peritoneal inflammation and irritation; produced by mesothelial and epithelial cells.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Extensive O-glycosylation modulates immune evasion and tumor progression.", "mechanism": "Highly elevated in epithelial ovarian cancer due to overexpression by tumor cells.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "N-glycosylation affects stability and secretion.", "mechanism": "Elevated in ovarian malignancy, especially serous and endometrioid carcinoma.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "medium", "disease": "Peritoneal Tuberculosis (PTB)", "glycan_involvement": "N-glycosylation present, but not directly linked to PTB mechanism.", "mechanism": "Usually normal or mildly elevated; helps differentiate PTB from ovarian cancer.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Multiple N-glycosylation sites modulate cell adhesion and immune interactions.", "mechanism": "Elevated in colorectal and other adenocarcinomas; used for diagnosis and monitoring.", "protein": "CEA (CEACAM5)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "high", "disease": "Peritoneal Tuberculosis (PTB)", "glycan_involvement": "N-glycosylation not directly involved in PTB mechanism.", "mechanism": "Remains low in PTB; helps exclude malignancy when ascites and elevated CA-125 are present.", "protein": "CEA (CEACAM5)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "medium", "disease": "Tubo-Ovarian Abscess (TOA)", "glycan_involvement": "O-glycosylation supports secretion during inflammation.", "mechanism": "Can be elevated due to pelvic inflammation, but less specific than for PTB or ovarian cancer.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "medium", "disease": "Tubo-Ovarian Abscess (TOA)", "glycan_involvement": "N-glycosylation present.", "mechanism": "Usually not elevated; helps distinguish TOA from ovarian cancer.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "low", "disease": "Colorectal Cancer", "glycan_involvement": "O-glycosylation modulates immune response.", "mechanism": "May be mildly elevated in advanced disease with peritoneal involvement.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "N-glycosylation affects cell adhesion.", "mechanism": "Occasionally elevated in ovarian cancer, but less sensitive than CA-125 or HE4.", "protein": "CEA (CEACAM5)", "relationship_type": "biomarker", "source_pmcid": "PMC12385388" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "AST is N-glycosylated, which may affect its stability and secretion during liver injury.", "mechanism": "Elevated AST levels are associated with increased severity and mortality in COVID-19 patients.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ALT is N-glycosylated, influencing its serum levels in liver dysfunction.", "mechanism": "ALT levels are elevated in deceased COVID-19 patients, but less predictive than AST for severity.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Platelet surface glycoproteins mediate immune and coagulation responses, altered in inflammation.", "mechanism": "Platelet count is used in FIB-4 and APRI indices; lower counts are linked to worse outcomes.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates lymphocyte trafficking and immune signaling.", "mechanism": "Lymphocyte count is used in ALRI and NLR indices; lymphopenia predicts severity and mortality.", "protein": "Lymphocyte Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Neutrophil glycoproteins regulate adhesion and migration during inflammation.", "mechanism": "Neutrophil count is used in NLR and SII indices; neutrophilia is associated with poor prognosis.", "protein": "Neutrophil Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "N-glycosylation may affect AST's serum stability in chronic liver disease.", "mechanism": "AST is a component of FIB-4 and APRI indices, which are validated for liver fibrosis assessment.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation may reflect hepatocyte dysfunction.", "mechanism": "AST/ALT ratio >1 is indicative of severe hepatocyte damage and cirrhosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation changes may occur in cancer progression.", "mechanism": "FIB-4 index, including AST, predicts risk for hepatocellular carcinoma.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Platelet glycoproteins mediate vascular integrity and inflammation.", "mechanism": "Low platelet count in FIB-4/APRI is associated with ARDS risk in severe COVID-19.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation affects lymphocyte survival and function during severe infection.", "mechanism": "Lymphopenia (low lymphocyte count) is a predictor of ARDS in COVID-19.", "protein": "Lymphocyte Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12385445" }, { "confidence": "high", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "CA19-9 is a sialylated glycan epitope on mucin-type glycoproteins.", "mechanism": "Elevated serum CA19-9 reflects tumor burden and is used for diagnosis and monitoring.", "protein": "CA19-9 (Sialyl-Lewis A)", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "high", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Aberrant O-glycosylation alters MUC1 antigenicity and function.", "mechanism": "Overexpressed in tumor cells; detected by IHC for diagnosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Altered glycosylation affects mucin secretion and tumor microenvironment.", "mechanism": "Negative staining helps distinguish pancreatic from other adenocarcinomas.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Glycosylation modulates mucin function in tumor biology.", "mechanism": "Negative staining supports diagnosis; positive in some GI tumors.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Intermediate filament glycoprotein; glycosylation affects stability.", "mechanism": "Strong positivity in tumor cells by IHC; supports epithelial origin.", "protein": "CK19 (KRT19)", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Glycosylation modulates cell adhesion and immune recognition.", "mechanism": "Partial positivity in tumor cells; used in differential diagnosis.", "protein": "Mesothelin", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Abnormal \u03b3-carboxylation (post-translational modification) alters glycoform.", "mechanism": "Elevated in serum; reflects abnormal prothrombin glycoform in malignancy.", "protein": "PIVKA-II (Des-gamma-carboxy prothrombin)", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "EpCAM is a glycoprotein; glycosylation affects cell adhesion.", "mechanism": "Positive staining supports epithelial tumor origin.", "protein": "BerEP4 (EpCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "high", "disease": "Malignancy-associated retroperitoneal fibrosis (maRPF)", "glycan_involvement": "Reflects tumor-associated glycosylation changes.", "mechanism": "Persistent elevation suggests underlying malignancy as cause of fibrosis.", "protein": "CA19-9 (Sialyl-Lewis A)", "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "medium", "disease": "Cancer of unknown primary (CUP)", "glycan_involvement": "Aberrant glycosylation patterns help distinguish tumor types.", "mechanism": "IHC positivity aids in narrowing tissue of origin in CUP cases.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385468" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Albumin glycosylation affects its stability and binding properties.", "mechanism": "Albumin is used as a replacement fluid in TPE to restore oncotic pressure and bind toxins.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385475" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "Glycosylation is essential for clotting factor function and stability.", "mechanism": "Plasma glycoproteins (including clotting factors) are replaced during TPE to correct coagulopathy in ALF.", "protein": "Fresh Frozen Plasma Glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385475" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "N-glycosylation is critical for fibrinogen secretion and function.", "mechanism": "Decreased levels indicate liver synthetic dysfunction and bleeding risk.", "protein": "Coagulation Factors (e.g., Fibrinogen)", "relationship_type": "biomarker", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Fc glycosylation regulates immunoglobulin effector functions.", "mechanism": "Immunoglobulins in plasma help modulate immune response and may be removed or replaced during TPE.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Glycosylation modulates haptoglobin\u2019s clearance and immune interactions.", "mechanism": "Levels change in response to inflammation and liver injury.", "protein": "Acute Phase Glycoproteins (e.g., Haptoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Hepatic Encephalopathy", "glycan_involvement": "Glycosylation may affect albumin\u2019s binding capacity.", "mechanism": "Albumin binds ammonia and other toxins, reducing neurotoxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Drug-Induced Liver Injury (DILI)", "glycan_involvement": "Glycosylation ensures proper protein folding and function.", "mechanism": "Plasma exchange removes toxic metabolites and replaces lost plasma proteins.", "protein": "Fresh Frozen Plasma Glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385475" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation required for factor stability.", "mechanism": "Replacement via plasma exchange corrects bleeding risk.", "protein": "Coagulation Factors (e.g., Fibrinogen)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "Glycosylation affects immunoglobulin antiviral activity.", "mechanism": "Immunoglobulins help neutralize viral particles and modulate inflammation.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC12385475" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "Glycosylation patterns change during acute phase response.", "mechanism": "Levels reflect acute inflammatory response to viral infection.", "protein": "Acute Phase Glycoproteins (e.g., Haptoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC12385475" }, { "confidence": "high", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation affects MDR3 stability and trafficking.", "mechanism": "Mutations impair phosphatidylcholine transport, leading to bile acid accumulation and hepatocellular injury.", "protein": "MDR3 (ABCB4)", "relationship_type": "causal", "source_pmcid": "PMC12385523" }, { "confidence": "high", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation required for BSEP membrane localization.", "mechanism": "Mutations reduce bile acid export from hepatocytes, causing cholestasis.", "protein": "BSEP (ABCB11)", "relationship_type": "causal", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation may affect membrane stability.", "mechanism": "Mutations disrupt phospholipid asymmetry, increasing hepatocyte vulnerability to bile acids.", "protein": "ATP8B1", "protein_enriched": { "function": "Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity t", "gene_name": "SEC14L2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O76054" }, "relationship_type": "causal", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "FXR agonists restore bile acid homeostasis and protect placental function.", "protein": "FXR (NR1H4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation influences zonulin secretion and function.", "mechanism": "Elevated zonulin correlates with ICP severity and poor response to UDCA.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Heparan sulfate glycosylation critical for cytokine/growth factor interactions.", "mechanism": "High syndecan-1 levels associate with inadequate UDCA response.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Heparan sulfate glycosylation modulates cellular healing.", "mechanism": "Elevated glypican-3 linked to poor UDCA response.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation affects enzyme activity and secretion.", "mechanism": "Increased autotaxin activity elevates LPA, contributing to pruritus.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "causal", "source_pmcid": "PMC12385523" }, { "confidence": "low", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation may regulate BACH1 stability.", "mechanism": "BACH1 elevation in placenta enhances oxidative stress and impairs angiogenesis.", "protein": "BACH1", "protein_enriched": { "function": "Transcriptional regulator that acts as a repressor or activator, depending on the context. Binds to NF-E2 DNA binding sites. Plays important roles in coordinating transcription activation and repressi", "gene_name": "BACH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14867" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385523" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Activated by sulfated progesterone metabolites, mediates pruritus.", "protein": "TGR5 (GPBAR1)", "protein_enriched": { "function": "Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macr", "gene_name": "GPBAR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8TDU6" }, "relationship_type": "causal", "source_pmcid": "PMC12385523" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 2D", "glycan_involvement": "\u03b1-sarcoglycan is a glycoprotein; glycosylation is essential for complex stability.", "mechanism": "Mutations in \u03b1-sarcoglycan gene disrupt the sarcoglycan complex, leading to muscle fiber instability and progressive muscular dystrophy.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Dystrophin interacts with glycoprotein complexes; glycosylation of associated proteins is critical.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex, causing membrane instability and muscle degeneration.", "protein": "dystrophin", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "high", "disease": "Congenital muscular dystrophy (integrin-deficient)", "glycan_involvement": "Integrins are glycoproteins; glycosylation affects ligand binding and stability.", "mechanism": "Deficiency of \u03b17-integrin impairs force transmission and muscle integrity, resulting in muscular dystrophy.", "protein": "\u03b17\u03b21 integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "high", "disease": "Muscular dystrophy with myositis (mdm)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Titin N2A region mutation leads to early-onset, progressive muscle-wasting disease with diaphragm dysfunction.", "protein": "titin", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "high", "disease": "Progressive muscular dystrophy", "glycan_involvement": "Glycosylation of DGC components is essential for complex assembly and function.", "mechanism": "Disruption of DGC (including glycoprotein components) leads to muscle fiber instability and degeneration.", "protein": "dystrophin-glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Heavily glycosylated; glycosylation is critical for ligand binding.", "mechanism": "Disrupted association with sarcospan and sarcoglycans impairs extracellular matrix linkage, leading to muscle degeneration.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "medium", "disease": "Congenital muscular dystrophy", "glycan_involvement": "Glycosylation required for ECM interactions.", "mechanism": "Deficiency or abnormality in merosin disrupts muscle-ECM interactions, causing muscle weakness.", "protein": "merosin (laminin \u03b12)", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "high", "disease": "Muscle necrosis", "glycan_involvement": "Complex is composed of glycoproteins; glycosylation is essential for stability.", "mechanism": "Loss of sarcoglycan complex integrity leads to muscle fiber necrosis and progressive dystrophy.", "protein": "sarcoglycan complex", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "medium", "disease": "Diaphragm muscle atrophy", "glycan_involvement": "Integrin glycosylation modulates function.", "mechanism": "Integrin deficiency alters diaphragm compliance and viscoelasticity, contributing to atrophy.", "protein": "\u03b17\u03b21 integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "medium", "disease": "Respiratory insufficiency", "glycan_involvement": "Glycosylation of DGC components is required for proper diaphragm mechanics.", "mechanism": "DGC disruption in diaphragm leads to impaired respiratory muscle function.", "protein": "dystrophin-glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12385653" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation affects ApoB-100 secretion and lipoprotein metabolism.", "mechanism": "ApoB-100 is a major component of triglyceride-rich lipoproteins, which accumulate in NAFLD.", "protein": "Apolipoprotein B-100", "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation modulates ApoA-I stability and HDL function.", "mechanism": "ApoA-I is the main protein in HDL; low HDL is associated with NAFLD.", "protein": "Apolipoprotein A-I", "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "HDL contains glycoproteins; glycosylation affects HDL metabolism.", "mechanism": "Low HDL levels are a diagnostic and pathophysiological marker for NAFLD.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation of apolipoproteins modulates lipoprotein clearance.", "mechanism": "Hepatic accumulation of triglyceride-rich lipoproteins drives steatosis.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385797" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in NAFLD, reflecting hepatic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation status can change in liver disease.", "mechanism": "Serum albumin decreases with advanced liver fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALP is N-glycosylated; glycosylation affects its serum levels.", "mechanism": "ALP is elevated in NAFLD, reflecting hepatobiliary involvement.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is glycosylated; glycan changes may occur in liver disease.", "mechanism": "AST is elevated in NAFLD due to hepatocyte injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is glycosylated; glycan changes may reflect liver status.", "mechanism": "ALT is elevated in NAFLD and used in non-invasive scoring.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "CRP is a marker of systemic inflammation, elevated in metabolic syndrome and CVD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385797" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "L1CAM is a heavily glycosylated membrane protein; glycosylation affects its cell adhesion and signaling functions.", "mechanism": "High L1CAM expression is associated with high-grade histology, advanced stage, lymphovascular invasion, and poor prognosis; acts as a prognostic biomarker.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation may affect antibody binding and L1CAM shedding.", "mechanism": "Preclinical studies show anti-L1CAM antibodies can suppress tumor growth and chemoresistance.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation may modulate L1CAM-mediated signaling and drug resistance.", "mechanism": "L1CAM expression predicts platinum-based chemotherapy resistance.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation status may influence L1CAM stability and function.", "mechanism": "L1CAM is a poor prognostic factor in non-specific molecular profile subgroup (p53 normal, MMR proficient, POLE wild-type).", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "low", "disease": "Endometrial cancer", "glycan_involvement": "Proteolytic cleavage and glycosylation generate soluble L1CAM forms.", "mechanism": "Serum L1CAM levels variably associated with lymph node metastasis and poor outcome.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Adenomatoid tumor", "glycan_involvement": "Glycosylation required for cell surface localization and detection.", "mechanism": "L1CAM expression is a surrogate marker for TRAF7 mutations in diagnosis.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Well-differentiated papillary mesothelial tumor", "glycan_involvement": "Glycosylation affects L1CAM detection and function.", "mechanism": "L1CAM is upregulated via NF-\u03baB signaling due to TRAF7 mutations.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may modulate L1CAM-mediated cell migration.", "mechanism": "L1CAM expression is associated with poor prognosis and specific SNPs linked to cancer risk.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Glycosylation influences cell adhesion and migration.", "mechanism": "L1CAM is expressed in melanoma and may contribute to tumor progression.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "low", "disease": "Renal cell cancer", "glycan_involvement": "Glycosylation affects L1CAM function in cell\u2013cell interactions.", "mechanism": "L1CAM is expressed in renal cell cancer and may be involved in tumorigenesis.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385864" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "SCFA production involves fermentation of dietary glycans; glycoprotein expression may mediate host interaction.", "mechanism": "Increased abundance correlates with reduced obesity; produces SCFAs supporting gut barrier.", "protein": "Adlercreutzia muris", "relationship_type": "protective", "source_pmcid": "PMC12385880" }, { "confidence": "medium", "disease": "Liver steatosis", "glycan_involvement": "Fermentation of glycans to SCFAs may reduce hepatic fat deposition.", "mechanism": "Increased abundance associated with reduced hepatic triglyceride accumulation.", "protein": "Adlercreutzia muris", "relationship_type": "protective", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "NAFLD", "glycan_involvement": "Potential glycoprotein-mediated host interaction; not specified.", "mechanism": "Increased abundance observed in NAFLD patients; functional role unclear.", "protein": "Cutibacterium acnes", "relationship_type": "biomarker", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Possible involvement in glycan metabolism affecting lipid absorption.", "mechanism": "Abundance positively correlates with serum triglycerides.", "protein": "Massiliimalia timonensis", "relationship_type": "biomarker", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Carbohydrate metabolism may influence host lipid metabolism.", "mechanism": "Abundance positively correlates with serum triglycerides.", "protein": "Faecousia sp000434635", "relationship_type": "biomarker", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Fermentation of dietary glycans; may impact host lipid metabolism.", "mechanism": "Abundance positively correlates with serum triglycerides.", "protein": "Ruminococcaceae (family)", "relationship_type": "biomarker", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Likely involved in glycan metabolism affecting lipid profiles.", "mechanism": "Abundance positively correlates with total and non-HDL cholesterol.", "protein": "Erysipelotrichales (order)", "relationship_type": "biomarker", "source_pmcid": "PMC12385880" }, { "confidence": "low", "disease": "Liver steatosis", "glycan_involvement": "Bacteroidetes often degrade host and dietary glycans; may modulate inflammation.", "mechanism": "Increased abundance associated with improved outcomes in other liver disease models.", "protein": "Paramuribaculum intestinale", "relationship_type": "protective (putative)", "source_pmcid": "PMC12385880" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its clearance and receptor binding.", "mechanism": "Elevated LDL levels are associated with increased cardiovascular risk; breakfast rich in \u03b2-glucans reduces LDL.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL glycosylation influences anti-inflammatory properties.", "mechanism": "HDL levels are protective; breakfast composition (e.g., eggs, oatmeal) modulates HDL/LDL ratio.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and receptor interaction.", "mechanism": "Breakfast skipping impairs insulin sensitivity, increasing diabetes risk.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates secretion and activity.", "mechanism": "Egg-based breakfasts reduce TNF-\u03b1 in type 2 diabetes patients, lowering inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "SIRT1 glycosylation may regulate activity and stability.", "mechanism": "Early time-restricted feeding increases SIRT1, promoting longevity and metabolic health.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12385972" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Ghrelin O-glycosylation affects secretion and appetite regulation.", "mechanism": "Egg breakfasts lower ghrelin, increasing satiety and reducing obesity risk.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "low", "disease": "Cardiovascular Disease", "glycan_involvement": "LC3A glycosylation may affect autophagic flux.", "mechanism": "Early breakfast increases autophagy marker LC3A, improving metabolic health.", "protein": "LC3A", "relationship_type": "protective", "source_pmcid": "PMC12385972" }, { "confidence": "low", "disease": "Chronic Inflammation", "glycan_involvement": "AST glycosylation influences enzyme activity.", "mechanism": "Egg breakfasts reduce AST, indicating lower inflammation in diabetes.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12385972" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "PPAR\u03b1 glycosylation modulates transcriptional activity.", "mechanism": "Breakfast skipping alters PPAR\u03b1 expression, disrupting lipid metabolism and increasing obesity risk.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "causal", "source_pmcid": "PMC12385972" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "SREBP-1c glycosylation affects nuclear translocation and activity.", "mechanism": "Breakfast omission disrupts SREBP-1c, leading to abnormal lipid synthesis and dyslipidemia.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12385972" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "Glycosylation required for MDR1 membrane localization and function.", "mechanism": "PXR activation upregulates MDR1, increasing drug efflux and resistance in cancer cells.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386191" }, { "confidence": "high", "disease": "Drug-Induced Liver Injury (DILI)", "glycan_involvement": "Glycosylation affects MRP2 trafficking and stability.", "mechanism": "PXR regulates MRP2 expression, affecting hepatic excretion of drugs and bilirubin.", "protein": "MRP2 (ABCC2)", "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates CD36 ligand binding and fatty acid transport.", "mechanism": "PXR activation upregulates PPAR\u03b3 and CD36, increasing hepatic fatty acid uptake and steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "B3GALT5 catalyzes glycan synthesis for mucosal protection.", "mechanism": "Intestinal PXR activation upregulates B3GALT5, maintaining barrier integrity and preventing inflammation.", "protein": "\u03b2-1,3-galactosyltransferase 5 (B3GALT5)", "protein_enriched": { "function": "Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues. Prefere", "gene_name": "CHST7", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G92551JA", "G80920RR", "G88520YF", "G02852RP" ], "uniprot_id": "Q9NS84" }, "relationship_type": "protective", "source_pmcid": "PMC12386191" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for NPC1L1 trafficking and cholesterol uptake.", "mechanism": "PXR activation increases NPC1L1 expression, promoting cholesterol absorption and foam cell formation.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation influences CXCL2 secretion and activity.", "mechanism": "PXR suppresses CXCL2 via NF-\u03baB/AP-1 inhibition, reducing inflammation in obesity.", "protein": "CXCL2", "protein_enriched": { "function": "Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-", "gene_name": "CXCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19875" }, "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates POSTN extracellular matrix interactions.", "mechanism": "PXR activation inhibits NF-\u03baB-mediated POSTN transcription, reducing EMT and metastasis.", "protein": "POSTN (Periostin)", "relationship_type": "protective", "source_pmcid": "PMC12386191" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "MASP1 is a glycoprotein involved in complement activation.", "mechanism": "AFB1 and HBV suppress FTCD-AS1-PXR-MASP1 axis, promoting hepatic injury and HCC.", "protein": "MASP1", "protein_enriched": { "function": "Membrane-anchored forms may play a role in cellular adhesion", "gene_name": "MSLN", "glycan_count": 31, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G23505EP", "G37881RL", "G39595FH", "G45395BF", "G56784JY", "G90382BL", "G02030ZB", "G13694XX", "G22310AV", "G37399XV", "G38663NM", "G47748JZ", "G48414YA", "G51640FO", "G72667IM", "G80920RR", "G82463GQ", "G84452RH", "G91473PK", "G12793SR", "G25418HZ", "G27058EU", "G30740WO", "G33791AF", "G47518TP", "G52527GH", "G55412XP", "G57888GL", "G82830MN", "G41247ZX", "G49108TO" ], "uniprot_id": "Q13421" }, "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects SLC27A4 membrane localization.", "mechanism": "PXR activation upregulates SLC27A4, increasing fatty acid uptake and liver steatosis.", "protein": "SLC27A4 (FATP4)", "protein_enriched": { "function": "Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane (PubMed:12556534, PubMed:20530735, PubMed:21395585, PubMed:28178239). Also fun", "gene_name": "SLC27A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6PCB7" }, "relationship_type": "causal", "source_pmcid": "PMC12386191" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation essential for MDR1 function.", "mechanism": "PXR activation upregulates MDR1, contributing to 5-FU resistance; inhibition sensitizes cancer cells.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386191" }, { "confidence": "high", "disease": "Tubulointerstitial Fibrosis", "glycan_involvement": "Glycosylation modulates TNC's ECM interactions and fibrogenic activity.", "mechanism": "Upregulated TNC promotes ECM remodeling and fibrosis in kidney tubulointerstitium.", "protein": "Tenascin-C (TNC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation required for Klotho stability and function.", "mechanism": "Reduced Klotho expression correlates with kidney dysfunction, oxidative stress, and fibrosis.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Kidney Fibrosis", "glycan_involvement": "Glycosylation affects TGF-\u03b2 secretion and receptor binding.", "mechanism": "TGF-\u03b2 signaling drives mesenchymal expansion and ECM deposition, leading to fibrosis.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Kidney Fibrosis", "glycan_involvement": "N-glycosylation required for receptor trafficking and ligand binding.", "mechanism": "Upregulation of TGF-\u03b2R2 enhances TGF-\u03b2 signaling and fibrotic response.", "protein": "TGF-\u03b2R2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Kidney Fibrosis", "glycan_involvement": "Glycosylation modulates PDGF-\u03b2 stability and receptor interaction.", "mechanism": "PDGF-\u03b2 signaling promotes fibroblast proliferation and ECM production.", "protein": "PDGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Kidney Fibrosis", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "PDGF-R\u03b2 activation drives fibrogenic signaling in renal cells.", "protein": "PDGF-R\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386213" }, { "confidence": "medium", "disease": "Kidney Fibrosis", "glycan_involvement": "Glycosylation may affect filament assembly and cell migration.", "mechanism": "Elevated vimentin marks mesenchymal transition and fibrotic remodeling.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386213" }, { "confidence": "medium", "disease": "Glomerulosclerosis", "glycan_involvement": "Potential O-glycosylation modulates actin dynamics.", "mechanism": "Increased \u03b1-SMA indicates activated myofibroblasts and mesangial expansion.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12386213" }, { "confidence": "medium", "disease": "Kidney Fibrosis", "glycan_involvement": "Glycosylation may regulate SMAD7 stability.", "mechanism": "SMAD7 inhibits TGF-\u03b2 signaling; reduced SMAD7 enhances fibrosis.", "protein": "SMAD7", "protein_enriched": { "function": "Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associati", "gene_name": "SMAD7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15105" }, "relationship_type": "protective", "source_pmcid": "PMC12386213" }, { "confidence": "medium", "disease": "Inflammatory kidney injury", "glycan_involvement": "Glycosylation influences TNC's immunomodulatory functions.", "mechanism": "TNC upregulation associated with inflammation and tissue remodeling in kidney.", "protein": "Tenascin-C (TNC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386213" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "gp210 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-gp210 autoantibodies are highly specific for PBC and predict poor prognosis and UDCA non-response.", "protein": "gp210", "protein_enriched": { "function": "Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and t", "gene_name": "JUP", "glycan_count": 12, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G43089EG", "G52527GH", "G75983OB", "G13694XX", "G22310AV", "G56784JY", "G57888GL", "G06356OH", "G11629QQ", "G84452RH" ], "uniprot_id": "P14923" }, "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC12386217" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "sp100 is a glycoprotein; glycosylation may influence immune recognition.", "mechanism": "Anti-sp100 autoantibodies are highly specific for PBC and associated with worse prognosis.", "protein": "sp100", "protein_enriched": { "function": "Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation a", "gene_name": "SP100", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P23497" }, "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC12386217" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "AE2 is a glycoprotein; glycosylation may affect membrane localization and function.", "mechanism": "AE2 deficiency impairs bicarbonate secretion, disrupting the 'bicarbonate umbrella' and increasing cholangiocyte susceptibility to bile acid toxicity.", "protein": "AE2 (SLC4A2)", "protein_enriched": { "function": "Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry (PubMed:10347222, PubMed:12403779, PubMed:14578046, PubMed:14736710). Mediates the sodium-dependen", "gene_name": "SLC4A7", "glycan_count": 11, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G80920RR", "G41840AI", "G41429FA", "G03644CB", "G28541PG", "G31852PQ", "G40574BA", "G41247ZX", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q9Y6M7" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12386217" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "CFTR is a glycoprotein; glycosylation is critical for trafficking and function.", "mechanism": "Reduced CFTR expression impairs chloride-driven bicarbonate secretion, contributing to cholangiocyte injury.", "protein": "CFTR", "relationship_type": "causal/protective", "source_pmcid": "PMC12386217" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "PDC-E2 is a glycoprotein; glycosylation may affect immune recognition.", "mechanism": "PDC-E2 is the main mitochondrial autoantigen targeted by AMA; its persistence in apoptotic blebs triggers immune-mediated bile duct injury.", "protein": "PDC-E2", "protein_enriched": { "function": "As part of the pyruvate dehydrogenase complex, catalyzes the transfers of an acetyl group to a lipoic acid moiety (Probable). The pyruvate dehydrogenase complex, catalyzes the overall conversion of py", "gene_name": "DLAT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10515" }, "relationship_type": "causal/autoantigen", "source_pmcid": "PMC12386217" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "HLA class II is a glycoprotein; glycosylation modulates peptide binding and immune interactions.", "mechanism": "Cholangiocyte HLA class II expression enables antigen presentation, promoting T cell-mediated autoimmunity.", "protein": "HLA class II", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12386217" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "KLHL12 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-KLHL12 autoantibodies are diagnostic markers in AMA-negative PBC.", "protein": "KLHL12", "protein_enriched": { "function": "Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). Th", "gene_name": "KLHL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q53G59" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386217" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "HK-1 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-HK-1 autoantibodies are diagnostic markers in AMA-negative PBC.", "protein": "Hexokinase 1 (HK-1)", "protein_enriched": { "function": "Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate", "gene_name": "HK1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G47950XN" ], "uniprot_id": "P19367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386217" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "Secretin receptor is glycosylated; glycosylation may affect receptor function.", "mechanism": "Secretin receptor activation restores bicarbonate secretion and protects against bile duct loss in PBC models.", "protein": "Secretin receptor", "protein_enriched": { "function": "G protein-coupled receptor activated by secretin (SCT), which is involved in different processes such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:2533297", "gene_name": "SCTR", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P47872" }, "relationship_type": "protective/therapeutic target", "source_pmcid": "PMC12386217" }, { "confidence": "low", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "Aquaporin 1 is a glycoprotein; glycosylation affects membrane localization.", "mechanism": "Aquaporin 1 facilitates water movement for bile formation; reduced expression impairs bile flow.", "protein": "Aquaporin 1", "relationship_type": "protective", "source_pmcid": "PMC12386217" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "AREG glycosylation in extracellular domain may affect receptor binding and shedding.", "mechanism": "AREG overexpression drives fibroblast proliferation, EMT, and collagen deposition via EGFR and PI3K/Akt/MAPK pathways; neutralizing AREG or gene silencing reduces fibrosis.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12386221" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE) / Lupus Nephritis (LN)", "glycan_involvement": "Glycosylation may modulate AREG stability and secretion.", "mechanism": "AREG overexpression in leukocytes correlates with renal fibrosis severity; cell source-dependent effects (macrophage/Treg-derived AREG may be protective or pro-fibrotic).", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "biomarker/therapeutic_target/causal/protective", "source_pmcid": "PMC12386221" }, { "confidence": "medium", "disease": "Sj\u00f6gren\u2019s Disease (SjD)", "glycan_involvement": "AREG glycosylation in HB domain may affect cell surface interactions.", "mechanism": "AREG is overexpressed in salivary gland epithelium; promotes EMT and fibrosis via EGFR/ADAM17 axis and TGF-\u03b21/SMAD signaling.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Crohn\u2019s Disease (CD)", "glycan_involvement": "Glycosylation may influence AREG secretion and activity.", "mechanism": "AREG upregulated in fibrotic intestinal regions and Th17 cells; drives fibroblast activation and collagen deposition via PI3K/AKT pathway.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Radiation-induced Fibrosis", "glycan_involvement": "Glycosylation may affect AREG stability post-injury.", "mechanism": "AREG mediates fibrogenesis after irradiation; siRNA targeting AREG reduces organ damage and fibrosis.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "medium", "disease": "Atherosclerosis-associated Liver Fibrosis", "glycan_involvement": "Glycosylation may regulate AREG receptor interactions.", "mechanism": "AREG promotes hepatic stellate cell proliferation and collagen accumulation via PI3K/p38 signaling.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "ADAM17 glycosylation may affect protease activity and substrate specificity.", "mechanism": "ADAM17 mediates AREG ectodomain shedding, enabling EGFR activation and downstream fibrotic signaling.", "protein": "ADAM17 (TACE)", "protein_enriched": { "function": "Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammatio", "gene_name": "ADAM17", "glycan_count": 58, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G29184RN", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G49108TO", "G10819WX", "G25079LO", "G29299MO", "G45395BF", "G57776ZS", "G70101JE", "G70441OD", "G79666IR", "G80075MS", "G86880BF", "G87123QX", "G90659AW", "G02815KT", "G14260UH", "G27058EU", "G28541PG", "G37399XV", "G39188ZX", "G64527OM", "G82463GQ", "G83633GK", "G00912UN", "G10486CT", "G18647XP", "G20210JR", "G23294PN", "G40926MX", "G59626AS", "G60033FS", "G86182NS", "G04657PL", "G06356OH", "G08918WF", "G20425TQ", "G27947YN", "G43769HG", "G44215PV", "G46902YN", "G59536GA", "G65184UU", "G66163OV", "G70619PT", "G72790NZ", "G81263BG", "G86795LJ", "G95133RI", "G96577RX", "G99668VU", "G35029YA", "G48584BU", "G23719VF", "G72787SB" ], "uniprot_id": "P78536" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "EGFR glycosylation modulates ligand binding and receptor dimerization.", "mechanism": "EGFR activation by AREG drives fibroblast proliferation and EMT; EGFR inhibitors reduce fibrosis but have toxicity.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Renal Fibrosis (chronic kidney disease)", "glycan_involvement": "Glycosylation may affect renal AREG secretion and function.", "mechanism": "AREG upregulated in proximal tubule cells; SAMiRNA-AREG silencing reduces fibrosis and inflammatory markers.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Fibrosis in autoimmune diseases (general)", "glycan_involvement": "Glycosylation influences AREG processing and activity.", "mechanism": "AREG is a central mediator linking chronic inflammation to fibrosis via EGFR and TGF-\u03b21 pathways; potential biomarker for disease severity.", "protein": "Amphiregulin (AREG)", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts", "gene_name": "AREG", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G57321FI", "G49108TO" ], "uniprot_id": "P15514" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386221" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "Heavily N-glycosylated; glycosylation affects stability and detection.", "mechanism": "CEA is secreted by MTC cells; correlates with tumor burden, aggressiveness, and metastasis.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "Precursor is glycosylated; mature peptide less so.", "mechanism": "Produced by C-cells; elevated in MTC, used for diagnosis and monitoring.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "Glycosylation increases stability and half-life.", "mechanism": "Stable precursor of calcitonin; elevated in MTC, useful when calcitonin is ambiguous.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "medium", "disease": "Aggressive/metastatic MTC", "glycan_involvement": "Sialyl Lewis-A glycan epitope on glycoproteins; aberrant glycosylation in cancer.", "mechanism": "Elevated in advanced/metastatic MTC; correlates with tumor progression and mortality.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "medium", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "Glycosylation enhances serum stability.", "mechanism": "Elevated in metastatic MTC; correlates with tumor burden and therapy response.", "protein": "Pro-gastrin-releasing peptide", "protein_enriched": { "function": "Stimulates the release of gastrin and other gastrointestinal hormones (By similarity). Contributes to the perception of prurient stimuli and to the transmission of itch signals in the spinal cord that", "gene_name": "GRP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07492" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "medium", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "N-glycosylation affects secretion and detection.", "mechanism": "Secreted by neuroendocrine tumors including MTC; reflects tumor burden.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "high", "disease": "Aggressive/metastatic MTC", "glycan_involvement": "Glycosylation modulates serum half-life and immunoreactivity.", "mechanism": "High CEA and rapid doubling time indicate aggressive disease and poor prognosis.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Sialyl Lewis-A glycan on mucin-type glycoproteins.", "mechanism": "Used for diagnosis/monitoring; also elevated in some MTC cases.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "medium", "disease": "Paraneoplastic syndromes", "glycan_involvement": "Glycosylation increases stability.", "mechanism": "Elevated in MTC-related paraneoplastic syndromes (e.g., secretory diarrhea).", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "medium", "disease": "Other neuroendocrine neoplasms", "glycan_involvement": "N-glycosylation affects cross-reactivity.", "mechanism": "CEA can be elevated in other neuroendocrine tumors, but less specific than in MTC.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12386243" }, { "confidence": "high", "disease": "Congestive heart failure", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization of Pgp, impacting transport function.", "mechanism": "Pgp mediates efflux of cardiac glycosides (digoxin, digitoxin), affecting drug bioavailability and efficacy in heart failure treatment.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12386283" }, { "confidence": "high", "disease": "Arrhythmia", "glycan_involvement": "N-glycosylation affects Pgp stability and substrate specificity.", "mechanism": "Pgp inhibition or genetic variation increases plasma cardiac glycoside levels, leading to arrhythmia risk.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12386283" }, { "confidence": "high", "disease": "Drug toxicity (cardiac glycoside toxicity)", "glycan_involvement": "Glycosylation modulates Pgp's drug binding and efflux efficiency.", "mechanism": "Co-administration of Pgp inhibitors with cardiac glycosides increases drug plasma levels, causing toxicity.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12386283" }, { "confidence": "high", "disease": "Cancer (breast, lung, prostate, renal)", "glycan_involvement": "N-glycosylation influences Pgp expression and drug resistance phenotype.", "mechanism": "Pgp mediates efflux of chemotherapeutics and cardiac glycosides, contributing to multidrug resistance in cancer cells.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Congestive heart failure", "glycan_involvement": "Glycosylation of Na+/K+ ATPase may affect enzyme activity and drug binding.", "mechanism": "Cardiac glycosides inhibit Na+/K+ ATPase, increasing cardiac contractility.", "protein": "Na+/K+ ATPase", "protein_enriched": { "function": "This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the e", "gene_name": "ATP1A1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G36379GD", "G49108TO" ], "uniprot_id": "P05023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "N-glycosylation required for Pgp function.", "mechanism": "Pgp regulates cardiac glycoside disposition, impacting efficacy and safety in atrial fibrillation treatment.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Drug toxicity (cardiac glycoside toxicity)", "glycan_involvement": "Glycosylation status may serve as a biomarker for Pgp function.", "mechanism": "Pgp expression/activity predicts risk of cardiac glycoside toxicity.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Cancer (breast, lung, prostate, renal)", "glycan_involvement": "N-glycosylation modulates Pgp's protective function.", "mechanism": "Pgp effluxes toxic compounds, protecting normal tissues but conferring drug resistance to tumors.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Congestive heart failure", "glycan_involvement": "Glycosylation may influence Pgp's biomarker utility.", "mechanism": "Pgp activity correlates with cardiac glycoside clearance and therapeutic response.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Drug toxicity (cardiac glycoside toxicity)", "glycan_involvement": "Altered glycosylation could decrease Pgp affinity for cardiac glycosides.", "mechanism": "Targeting Pgp or modifying glycosylation may reduce cardiac glycoside toxicity.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386283" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Not directly studied; ABC transporters are glycoproteins, glycosylation may affect trafficking/function.", "mechanism": "Rare missense variant (p.Arg537His) segregates with familial ICP; likely disrupts ABC transporter function in hepatobiliary tissues.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "causal", "source_pmcid": "PMC12386353" }, { "confidence": "medium", "disease": "Gallstone disease", "glycan_involvement": "Not directly studied; possible impact via glycosylation-dependent trafficking.", "mechanism": "Variant carriers show early-onset gallstone disease, suggesting ABCB5 dysfunction affects bile composition or flow.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "causal", "source_pmcid": "PMC12386353" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Not specified.", "mechanism": "ABCB5 expression and mutation associated with susceptibility and presence in hepatic cancers.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386353" }, { "confidence": "low", "disease": "Idiopathic recurrent pregnancy loss", "glycan_involvement": "Not specified.", "mechanism": "Specific ABCB5 variant (rs17143187) associated with increased risk in a Korean cohort.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386353" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "Upregulated in high-risk atherosclerotic plaques, localized to macrophages.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386353" }, { "confidence": "low", "disease": "Obesity (childhood)", "glycan_involvement": "Not specified.", "mechanism": "Deletions including ABCB5 linked to childhood obesity in GWAS.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386353" }, { "confidence": "low", "disease": "Neurological instability after ischemic stroke", "glycan_involvement": "Not specified.", "mechanism": "Variants associated with early neurological instability post-stroke.", "protein": "ABCB5", "protein_enriched": { "function": "Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present ", "gene_name": "ABCB5", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q2M3G0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386353" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Glycosylation required for proper membrane localization.", "mechanism": "Pathogenic variants impair phosphatidylcholine transport, predisposing to ICP.", "protein": "ABCB4", "protein_enriched": { "function": "Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the", "gene_name": "ABCB4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21439" }, "relationship_type": "causal", "source_pmcid": "PMC12386353" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Glycosylation affects stability and trafficking.", "mechanism": "Pathogenic variants impair bile salt export pump, leading to bile acid accumulation.", "protein": "ABCB11", "relationship_type": "causal", "source_pmcid": "PMC12386353" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Not specified.", "mechanism": "Variants implicated in bile acid homeostasis; clinical relevance in ICP is uncertain.", "protein": "ATP8B1", "protein_enriched": { "function": "Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity t", "gene_name": "SEC14L2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O76054" }, "relationship_type": "causal", "source_pmcid": "PMC12386353" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "ISG15 is a glycoprotein; glycosylation may affect stability and immune signaling.", "mechanism": "Upregulated in PBMCs, reflects interferon-driven immune activation.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "IFI44L is glycosylated; glycan status may modulate antiviral activity.", "mechanism": "Upregulated, marks type I interferon response linked to disease severity.", "protein": "IFI44L", "protein_enriched": { "function": "This protein aggregates to form microtubular structures", "gene_name": "IFI44", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TCB0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "S100A9 glycosylation influences secretion and inflammatory signaling.", "mechanism": "Elevated in neutrophil activation, correlates with radiographic progression.", "protein": "S100A9", "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "Glycosylation modulates extracellular activity and immune interactions.", "mechanism": "Upregulated, reflects neutrophil degranulation and inflammation.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "LTF is heavily glycosylated; glycan structures affect antimicrobial function.", "mechanism": "Increased expression, marks neutrophil activation and innate immunity.", "protein": "LTF", "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis", "glycan_involvement": "Glycosylation may regulate enzyme activity and mitochondrial localization.", "mechanism": "Downregulated, indicating impaired mitochondrial \u03b2-oxidation and metabolic stress.", "protein": "ACADM", "protein_enriched": { "function": "Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids", "gene_name": "ACADM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11310" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386361" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis", "glycan_involvement": "N-glycosylation affects enzyme stability and function.", "mechanism": "Suppressed expression, links to defective fatty acid metabolism.", "protein": "CPT1A", "protein_enriched": { "function": "Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxid", "gene_name": "CPT1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50416" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386361" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis", "glycan_involvement": "Glycosylation may modulate enzymatic activity.", "mechanism": "Downregulated, correlates with bile acid depletion and metabolic imbalance.", "protein": "ACOT12", "protein_enriched": { "function": "Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity (PubMed:12881489, PubMed:17045234, PubMed:", "gene_name": "ALOXE3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYJ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis", "glycan_involvement": "Glycosylation critical for membrane localization and transporter function.", "mechanism": "Altered expression, hub in lipid transport and immune-metabolic network.", "protein": "ABCA13", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3M5F7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis", "glycan_involvement": "N-glycosylation modulates enzymatic activity and cell-surface expression.", "mechanism": "Inverse correlation with inflammatory lipid mediators, links vascular signaling to disease.", "protein": "ACE", "relationship_type": "biomarker", "source_pmcid": "PMC12386361" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Not directly discussed; as a propeptide, PENK may be glycosylated, which could affect stability.", "mechanism": "PENK levels are elevated in AHF due to increased synthesis in response to neurohormonal activation; reflects disease severity.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "high", "disease": "Worsening Renal Function (WRF)", "glycan_involvement": "Not specified; glycosylation may influence plasma stability and clearance.", "mechanism": "Elevated PENK predicts incident WRF in AHF patients, reflecting real-time changes in renal filtration.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Not specified.", "mechanism": "High PENK levels independently predict short- and long-term mortality in AHF.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "medium", "disease": "Cardiorenal Syndrome", "glycan_involvement": "Not specified.", "mechanism": "PENK reflects the interplay between cardiac and renal dysfunction in AHF.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "medium", "disease": "Cardiogenic Shock", "glycan_involvement": "Not specified.", "mechanism": "Patients with cardiogenic shock have higher PENK levels, reflecting severity.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "medium", "disease": "Pulmonary Edema", "glycan_involvement": "Not specified.", "mechanism": "Elevated PENK observed in patients with pulmonary edema as a form of AHF.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "medium", "disease": "Right Heart Failure", "glycan_involvement": "Not specified.", "mechanism": "PENK levels elevated in right HF, reflecting disease severity.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress", "gene_name": "PENK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01210" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386368" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI) in AHF", "glycan_involvement": "Not specified.", "mechanism": "PENK rises earlier than creatinine in AKI, indicating early renal dysfunction.", "protein": "Proenkephalin (PENK, proenkephalin 119\u2013159)", "protein_enriched": { "function": "Neuropeptide that competes with and mimic the effects of opiate drugs. 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"protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12386378" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Regulates immune tolerance and mucosal immunity, may modulate tumor microenvironment.", "protein": "Transforming Growth Factor Beta (TGF-\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386378" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Potential glycosylation modulates stability.", "mechanism": "Regulates immune cell activity, supports anti-tumor immunity.", "protein": "Proline-rich Polypeptides (PRPs)", "relationship_type": "protective", "source_pmcid": "PMC12386378" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "Specific glycoform (AFP-L3) is detected by unique glycosylation.", "mechanism": "AFP-L3 glycoform serves as a diagnostic and prognostic biomarker for hepatocellular carcinoma.", "protein": "Alpha-fetoprotein (AFP, AFP-L3 glycoform)", "relationship_type": "biomarker", "source_pmcid": "PMC12386378" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Altered glycosylation on tumor cell surface promotes metastasis.", "mechanism": "Increased Lewis antigens and branched N-glycans facilitate immune evasion and metastasis.", "protein": "Lewis antigens (cell surface glycans)", "relationship_type": "causal", "source_pmcid": "PMC12386378" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation changes drive metastatic behavior.", "mechanism": "Enhanced cell adhesion and metastatic potential via altered N-glycan branching.", "protein": "Branched N-glycans", "relationship_type": "causal", "source_pmcid": "PMC12386378" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycan structure enables selective microbial growth.", "mechanism": "Prebiotic effect promotes beneficial microbiota, increases SCFA production, reduces carcinogenic metabolites.", "protein": "Galacto-oligosaccharides (GOS)", "relationship_type": "protective", "source_pmcid": "PMC12386378" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Exosomal glycoproteins mediate targeting and uptake.", "mechanism": "Exosomes deliver therapeutic agents, induce cytotoxicity, ROS, inhibit migration, downregulate KRAS, restore p53, sensitize to paclitaxel.", "protein": "Exosome-associated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386378" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and A\u03b2 production.", "mechanism": "APP is cleaved to 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"G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", 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receptor-mediated transcytosis enables brain delivery of nanomedicines.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", 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"G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", 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RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386393" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ECM interactions.", "mechanism": "Altered fibronectin levels in vascular basement membrane are associated with AD pathology.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", 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"confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ECM structure and A\u03b2 interaction.", "mechanism": "Collagen IV alterations in vessels precede A\u03b2 deposition.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386393" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences transporter function and targeting.", "mechanism": "GLUT-1 targeting (via mannose) enhances nanoparticle delivery to the brain.", "protein": "Glucose transporter 1 (GLUT-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386393" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "O-glycosylation critical for mucin function and bacterial binding.", "mechanism": "Forms glycoprotein pellicle on teeth, limiting bacterial adhesion and biofilm formation.", "protein": "Salivary mucins", "relationship_type": "protective", "source_pmcid": "PMC12386417" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "N-glycosylation modulates antimicrobial activity.", "mechanism": "Antimicrobial glycoprotein in saliva inhibits growth of periodontal pathogens.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12386417" }, { "confidence": "medium", "disease": "Oral candidiasis", "glycan_involvement": "Glycosylation enhances peptide stability and activity.", "mechanism": "Glycosylated antimicrobial peptides limit Candida albicans overgrowth.", "protein": "Beta-defensins", "relationship_type": "protective", "source_pmcid": "PMC12386417" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "N-glycosylation essential for mucosal transport and function.", "mechanism": "Secretory IgA binds bacterial glycoproteins, preventing colonization.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12386417" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "Bacterial glycosylation required for host interaction.", "mechanism": "Glycosylated adhesins mediate attachment to tooth glycoprotein pellicle, promoting biofilm and acid production.", "protein": "Streptococcus mutans adhesins", "relationship_type": "causal", "source_pmcid": "PMC12386417" }, { "confidence": "medium", "disease": "Oral candidiasis", "glycan_involvement": "Mannan and other glycan structures mediate host-pathogen interactions.", "mechanism": "Cell wall glycoproteins facilitate adhesion and biofilm formation with oral bacteria.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12386417" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Glycosylation required for fimbrial assembly and function.", "mechanism": "Fimbrial glycoproteins promote colonization and immune evasion in periodontal tissues.", "protein": "Porphyromonas gingivalis fimbriae", "relationship_type": "causal", "source_pmcid": "PMC12386417" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Glycosylation facilitates host interaction.", "mechanism": "Surface glycoproteins mediate biofilm formation and acid production.", "protein": "Scardovia wiggsiae surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12386417" }, { "confidence": "medium", "disease": "Dental caries", "glycan_involvement": "Glycosylation involved in host colonization.", "mechanism": "Associated with caries lesions in adolescents; surface glycoproteins may mediate adhesion.", "protein": "Bifidobacterium longum surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12386417" }, { "confidence": "low", "disease": "Dental caries", "glycan_involvement": "Glycosylation mediates host-microbe interactions.", "mechanism": "Early colonizer from breast milk/skin, may compete with cariogenic bacteria.", "protein": "Staphylococcus epidermidis surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12386417" }, { "confidence": "high", "disease": "sCAP (with MASLD)", "glycan_involvement": "SEMA7A is a GPI-anchored glycoprotein; glycosylation required for cell surface localization and immune signaling.", "mechanism": "Elevated SEMA7A at admission predicts severity (SOFA, PSI, SMART-COP), organ failure, and poor outcomes; compartmentalized in lung (BALF) and correlates with liver disease severity.", "protein": "SEMA7A", "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "high", "disease": "sCAP (with MASLD)", "glycan_involvement": "SEMA4D is a transmembrane glycoprotein; glycosylation modulates receptor interactions and immune cell migration.", "mechanism": "SEMA4D levels and kinetics associate with mortality, shock, and need for IMV/CRRT; lack of SEMA4D upregulation in MASLD linked to impaired reparative signaling.", "protein": "SEMA4D", "protein_enriched": { "function": "Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling (PubMed:20877282). Regulates GABAergic synapse development (By similarity). Promotes the development of ", "gene_name": "SEMA4D", "glycan_count": 41, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G33791AF", "G37881RL", "G62765YT", "G14972EH", "G27058EU", "G34989PA", "G41071NU", "G43223CG", "G45395BF", "G52527GH", "G56784JY", "G71569SN", "G75983OB", "G80920RR", "G83460ZZ", "G83646BJ", "G87661QW", "G87672CW", "G49108TO", "G02815KT", "G05724UK", "G31852PQ", "G41247ZX", "G59536GA", "G70101JE", "G15664MX", "G46503DX", "G72747WU", "G57321FI", "G43417UB", "G13131HA", "G22310AV", "G37412TK", "G38663NM", "G40834TG", "G48414YA", "G57776ZS", "G80075MS", "G84452RH", "G85282JO", "G86880BF" ], "uniprot_id": "Q92854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "medium", "disease": "sCAP (with MASLD)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects secretion and immune modulation.", "mechanism": "Elevated at admission in MASLD; decline by day 5 associates with shock and organ failure; involved in endothelial permeability and neutrophil transmigration.", "protein": "SEMA3A", "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "medium", "disease": "AKI in sCAP", "glycan_involvement": "Secreted glycoprotein; glycosylation required for stability and function.", "mechanism": "Elevated baseline SEMA3F predicts CRRT requirement; correlates with inflammation (CRP, WBC, NLR).", "protein": "SEMA3F", "protein_enriched": { "function": "May play a role in cell motility and cell adhesion", "gene_name": "SEMA3F", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23294PN", "G25418HZ", "G62765YT", "G27058EU", "G40926MX", "G59536GA", "G83460ZZ", "G43417UB" ], "uniprot_id": "Q13275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "medium", "disease": "sCAP (with MASLD)", "glycan_involvement": "Transmembrane glycoprotein; glycosylation modulates cell migration and repair.", "mechanism": "Lower at admission in MASLD; lack of increase by day 5 associates with poor vascular repair and outcome.", "protein": "SEMA5A", "protein_enriched": { "function": "Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on int", "gene_name": "SEMA5A", "glycan_count": 2, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G02815KT", "G80920RR" ], "uniprot_id": "Q13591" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "high", "disease": "sCAP (with MASLD)", "glycan_involvement": "Chemokine glycoprotein; glycosylation affects chemotactic activity.", "mechanism": "Elevated at admission and in influenza MASLD; predicts IMV, shock, AKI, and poor outcome; decline over time associates with resolution.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "high", "disease": "sCAP (with MASLD)", "glycan_involvement": "Cytokine glycoprotein; glycosylation required for secretion and anti-inflammatory function.", "mechanism": "Elevated at admission and in MASLD with Mycoplasma/influenza; predicts IMV, AKI, shock; decline associates with outcome.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "medium", "disease": "Legionella/Mycoplasma/influenza pneumonia (with MASLD)", "glycan_involvement": "Cytokine glycoprotein; glycosylation affects stability and receptor binding.", "mechanism": "Elevated at admission in MASLD; sharp decline by day 5 associates with impaired host defense and poor outcome.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "medium", "disease": "sCAP (with MASLD)", "glycan_involvement": "Cytokine glycoprotein; glycosylation required for activation and signaling.", "mechanism": "Elevated at admission in MASLD; failure to upregulate by day 5 associates with impaired tissue repair and poor outcome.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "high", "disease": "Liver steatosis/fibrosis (MASLD)", "glycan_involvement": "GPI-anchored glycoprotein; glycosylation modulates hepatic stellate cell activation.", "mechanism": "Serum SEMA7A correlates with VCTE-CAP, LSM, FAST score, AST/ALT; reflects hepatic inflammation and fibrogenesis.", "protein": "SEMA7A", "relationship_type": "biomarker", "source_pmcid": "PMC12386445" }, { "confidence": "high", "disease": "Rafiq syndrome (RAFQS)", "glycan_involvement": "Defective N-glycan trimming in Golgi/ERAD pathway", "mechanism": "Bi-allelic loss-of-function mutations in MAN1B1 disrupt N-glycan processing, impairing glycoprotein maturation and ERAD, leading to RAFQS.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "Aberrant N-glycosylation affects neuronal development", "mechanism": "MAN1B1 deficiency impairs cortical neurogenesis, neuronal morphogenesis, and migration, resulting in intellectual disability.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Developmental delay", "glycan_involvement": "Impaired glycoprotein processing in neurons", "mechanism": "Loss of MAN1B1 function disrupts axon growth, dendrite formation, and spine maturation, causing developmental delay.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Defective N-glycosylation in neural circuits", "mechanism": "Subset of RAFQS patients with MAN1B1 mutations present with epilepsy, likely due to abnormal neuronal migration and maturation.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "medium", "disease": "Obesity (truncal)", "glycan_involvement": "Aberrant glycosylation of metabolic regulators", "mechanism": "MAN1B1 mutations associated with truncal obesity in RAFQS, possibly via altered glycoprotein signaling in metabolism.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "medium", "disease": "Muscular myopathy", "glycan_involvement": "Defective N-glycosylation of muscle proteins", "mechanism": "MAN1B1 deficiency linked to muscular myopathies in RAFQS, likely due to impaired glycoprotein maturation in muscle cells.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Facial dysmorphism", "glycan_involvement": "Impaired N-glycosylation in craniofacial morphogenesis", "mechanism": "MAN1B1 mutations cause craniofacial abnormalities via disrupted glycoprotein processing during development.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency (misfolded AAT accumulation)", "glycan_involvement": "Defective ERAD of N-glycosylated substrates", "mechanism": "MAN1B1 mutation slows degradation of misfolded N-glycosylated AAT variants, leading to their accumulation.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "medium", "disease": "Rafiq syndrome (RAFQS)", "glycan_involvement": "N-glycosylation status reflects MAN1B1 activity", "mechanism": "Misfolded N-glycosylated AAT variants used to assay MAN1B1 function in RAFQS cellular models.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation (CDG-II)", "glycan_involvement": "Defective N-glycan processing in Golgi", "mechanism": "MAN1B1 mutations define a CDG-II subtype by impairing glycan remodeling in the Golgi.", "protein": "MAN1B1", "protein_enriched": { "function": "Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc", "gene_name": "MAN1B1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB" ], "uniprot_id": "Q9UKM7" }, "relationship_type": "causal", "source_pmcid": "PMC12386520" }, { "confidence": "high", "disease": "Lung Neuroendocrine Tumor (LNET)", "glycan_involvement": "CD44 glycosylation modulates hyaluronic acid binding and signaling.", "mechanism": "Loss of CD44 expression is associated with increased risk of metastasis and poor prognosis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Lung Neuroendocrine Tumor (LNET)", "glycan_involvement": "CgA is heavily glycosylated, affecting secretion and stability.", "mechanism": "CgA is used for immunohistochemical diagnosis of neuroendocrine tumors.", "protein": "Chromogranin A (CgA)", "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Lung Neuroendocrine Tumor (LNET)", "glycan_involvement": "Glycosylation influences membrane localization.", "mechanism": "Synaptophysin is a diagnostic marker for neuroendocrine differentiation.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Lung Neuroendocrine Tumor (LNET)", "glycan_involvement": "Glycosylation affects cell adhesion properties.", "mechanism": "CD56 is used in immunohistochemistry to confirm neuroendocrine origin.", "protein": "Cluster of Differentiation 56 (CD56)", "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "medium", "disease": "Cluster B Carcinoids (subset of LNET)", "glycan_involvement": "N-glycosylation modulates receptor activation and signaling.", "mechanism": "High HER4 expression is associated with worse prognosis in cluster B carcinoids.", "protein": "HER4 (ERBB4)", "protein_enriched": { "function": "Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary ", "gene_name": "ERBB4", "glycan_count": 6, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G02815KT", "G22768VO", "G31852PQ", "G41247ZX", "G81315DD", "G22573RC" ], "uniprot_id": "Q15303" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "medium", "disease": "Cluster B Carcinoids (subset of LNET)", "glycan_involvement": "Glycosylation affects secretion and angiogenic activity.", "mechanism": "High ANGPTL3 expression correlates with poor prognosis in cluster B carcinoids.", "protein": "Angiopoietin-like protein 3 (ANGPTL3)", "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "medium", "disease": "Lung Neuroendocrine Tumor (LNET)", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 expression may predict response to immune checkpoint inhibitors.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Metastatic LNET", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "SSTR2 expression enables targeted therapy with somatostatin analogues and radioligand therapy.", "protein": "Somatostatin receptor 2 (SSTR2)", "protein_enriched": { "function": "Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC", "gene_name": "SSTR2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P30874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Atypical Carcinoid (AC)", "glycan_involvement": "Glycosylation modulates CD44-mediated signaling.", "mechanism": "CD44 loss enhances predictive value for disease progression when combined with OTP and Ki67.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Typical Carcinoid (TC)", "glycan_involvement": "Glycosylation influences cell-cell interactions.", "mechanism": "CD56 positivity supports diagnosis of typical carcinoid.", "protein": "Cluster of Differentiation 56 (CD56)", "relationship_type": "biomarker", "source_pmcid": "PMC12386555" }, { "confidence": "high", "disease": "Papillary Thyroid Carcinoma (PTC)", "glycan_involvement": "MMP-14 is a glycoprotein; glycosylation may affect stability and localization.", "mechanism": "Promotes ECM degradation, activates proMMP-2, facilitates tumor cell invasion and migration.", "protein": "MMP-14 (MT1-MMP)", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal conne", "gene_name": "MMP14", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G29068FM", "G49108TO" ], "uniprot_id": "P50281" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "PTC with lymph node metastasis", "glycan_involvement": "Glycosylation may modulate cell surface expression.", "mechanism": "Expression correlates with lymph node metastasis.", "protein": "MMP-14 (MT1-MMP)", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal conne", "gene_name": "MMP14", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G29068FM", "G49108TO" ], "uniprot_id": "P50281" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "PTC with advanced stage", "glycan_involvement": "Glycosylation may influence activity.", "mechanism": "Expression correlates with advanced tumor stage.", "protein": "MMP-14 (MT1-MMP)", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal conne", "gene_name": "MMP14", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G29068FM", "G49108TO" ], "uniprot_id": "P50281" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "PTC with extrathyroidal extension", "glycan_involvement": "Glycosylation may affect invasive potential.", "mechanism": "Expression correlates with extrathyroidal extension.", "protein": "MMP-14 (MT1-MMP)", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal conne", "gene_name": "MMP14", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G29068FM", "G49108TO" ], "uniprot_id": "P50281" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "PTC with high recurrence risk", "glycan_involvement": "Glycosylation may influence stability.", "mechanism": "Expression correlates with increased risk of recurrence.", "protein": "MMP-14 (MT1-MMP)", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix such as collagen (PubMed:8015608). Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal conne", "gene_name": "MMP14", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G29068FM", "G49108TO" ], "uniprot_id": "P50281" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "Papillary Thyroid Carcinoma (PTC)", "glycan_involvement": "MMP-2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Degrades ECM, promotes invasion; activity increased in PTC.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "Papillary Thyroid Carcinoma (PTC)", "glycan_involvement": "MMP-9 glycosylation affects secretion and stability.", "mechanism": "Highly elevated activity correlates with aggressive features and poor prognosis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "PTC with lymph node metastasis", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "Expression/activity correlates with lymph node metastasis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "medium", "disease": "PTC with lymph node metastasis", "glycan_involvement": "MMP-16 is glycosylated; glycosylation may affect function.", "mechanism": "Expression correlates with lymph node metastasis.", "protein": "MMP-16", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, ", "gene_name": "MMP17", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9ULZ9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "medium", "disease": "PTC with high recurrence risk", "glycan_involvement": "Glycosylation may influence stability.", "mechanism": "Expression correlates with increased risk of recurrence.", "protein": "MMP-16", "protein_enriched": { "function": "Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, ", "gene_name": "MMP17", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9ULZ9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386556" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding", "mechanism": "Target of anti-\u03b22-glycoprotein I antibodies, which promote thrombosis", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Antibody glycosylation modulates effector function", "mechanism": "Presence defines APS and increases risk of thrombosis", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "IgG glycosylation influences pathogenicity", "mechanism": "Correlates with disease activity and lupus nephritis", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antibody stability and immune complex formation", "mechanism": "Associated with SLE and DAH occurrence", "protein": "Anti-SSA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation required for complement activation", "mechanism": "Low C3 levels indicate active disease and risk for DAH", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation modulates complement function", "mechanism": "Low C4 levels associated with active SLE and DAH risk", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fc glycosylation alters inflammatory potential", "mechanism": "Autoantibody-mediated tissue injury in SLE and DAH", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386613" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects immune complex clearance", "mechanism": "Universal marker for SLE diagnosis and activity", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "medium", "disease": "Thromboembolic Events", "glycan_involvement": "Antibody glycosylation modulates thrombogenicity", "mechanism": "Promotes clot formation in APS and SLE", "protein": "Anti-\u03b22-glycoprotein I antibody", "relationship_type": "causal", "source_pmcid": "PMC12386613" }, { "confidence": "low", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects immune recognition", "mechanism": "Associated with SLE subset and possibly DAH", "protein": "Anti-SSB antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12386613" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "ATF6 is a glycoprotein; its ER localization and function depend on glycosylation.", "mechanism": "ATF6 activation promotes CRC cell growth, proliferation, and migration via UPR signaling.", "protein": "ATF6", "relationship_type": "causal", "source_pmcid": "PMC12386624" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Indirect; STK26 stabilizes glycoprotein ATF6.", "mechanism": "STK26 overexpression stabilizes p50ATF6, activating ATF6 pathway and promoting CRC progression.", "protein": "STK26", "relationship_type": "causal", "source_pmcid": "PMC12386624" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "ATF6 glycosylation may affect inhibitor binding and trafficking.", "mechanism": "Inhibition of ATF6 (Ceapin-A7) suppresses CRC cell growth and migration.", "protein": "ATF6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386624" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Indirect; effect mediated via ATF6 stabilization.", "mechanism": "STK26 inhibition (Hesperadin) reduces CRC tumor growth in vivo.", "protein": "STK26", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386624" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "HSPA5 is an N-glycosylated chaperone essential for ER stress response.", "mechanism": "HSPA5 is a downstream effector of ATF6; its expression correlates with CRC progression.", "protein": "HSPA5 (GRP78/BiP)", "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Not specified.", "mechanism": "XBP1 expression is regulated by ATF6 and correlates with CRC progression.", "protein": "XBP1", "protein_enriched": { "function": "Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic devel", "gene_name": "XBP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17861" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Not specified.", "mechanism": "DDIT3 is a downstream target of ATF6; reduced in STK26-deficient CRC cells.", "protein": "DDIT3 (CHOP)", "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "low", "disease": "Parkinson's Disease", "glycan_involvement": "ATF6 glycosylation may affect UPR signaling in neurodegeneration.", "mechanism": "UPR/ATF6 pathway enrichment observed in transcriptome analysis of STK26-deficient CRC cells.", "protein": "ATF6", "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "ATF6 glycosylation may affect UPR signaling in neurodegeneration.", "mechanism": "UPR/ATF6 pathway enrichment observed in transcriptome analysis of STK26-deficient CRC cells.", "protein": "ATF6", "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Indirect; via ATF6 stabilization.", "mechanism": "High STK26 expression correlates with poor prognosis and disease-free survival in CRC.", "protein": "STK26", "relationship_type": "biomarker", "source_pmcid": "PMC12386624" }, { "confidence": "high", "disease": "Trisomy 21 (Down syndrome)", "glycan_involvement": "Glycosylation affects PAPP-A stability and detection in serum.", "mechanism": "Low maternal serum PAPP-A is associated with increased risk of fetal trisomy 21.", "protein": "PAPP-A", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation modulates PAPP-A bioactivity and clearance.", "mechanism": "Low PAPP-A levels in first trimester are predictive of increased PE risk.", "protein": "PAPP-A", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "LPA glycosylation influences its plasma concentration and function.", "mechanism": "High LPA levels are linked to increased CVD risk due to pro-inflammatory and pro-thrombotic effects.", "protein": "LPA", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation affects LPA's interaction with vascular components.", "mechanism": "Elevated LPA may contribute to endothelial dysfunction in PE.", "protein": "LPA", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Pregnancy (normal physiology and complications)", "glycan_involvement": "Glycosylation is essential for PZP's immunomodulatory function.", "mechanism": "PZP shows extreme variability and is strongly associated with gestational age; altered levels may reflect pregnancy complications.", "protein": "PZP", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect CA1 stability and serum detection.", "mechanism": "Elevated and variable CA1 levels in pregnancy resemble those seen in cancer, suggesting shared regulatory mechanisms.", "protein": "CA1", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Trisomy 13/18/21", "glycan_involvement": "A2M glycosylation influences its protease inhibitory activity.", "mechanism": "A2M levels positively correlate with risk for trisomies 13, 18, and 21.", "protein": "A2M", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Trisomy 13/18/21", "glycan_involvement": "Glycosylation modulates IGFBP3's binding to IGFs.", "mechanism": "IGFBP3 levels weakly correlate with trisomy risk.", "protein": "IGFBP3", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "medium", "disease": "Trisomy 13/18/21", "glycan_involvement": "Glycosylation affects SERPING1's complement inhibitory function.", "mechanism": "SERPING1 levels show weak positive correlation with trisomy risk.", "protein": "SERPING1", "relationship_type": "biomarker", "source_pmcid": "PMC12386716" }, { "confidence": "high", "disease": "Pregnancy (reference marker)", "glycan_involvement": "Glycosylation maintains HPX stability and function.", "mechanism": "HPX is highly stable in pregnancy and may serve as a reference marker for normalization.", "protein": "HPX", "relationship_type": "protective", "source_pmcid": "PMC12386716" }, { "confidence": "high", "disease": "Primary sclerosing cholangitis (PSC)", "glycan_involvement": "TGF-\u03b2 is a secreted glycoprotein; glycosylation is required for secretion and activity.", "mechanism": "TGF-\u03b2 is a key profibrogenic cytokine driving hepatic stellate cell activation and fibrosis in PSC.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Apelin is a glycopeptide; glycosylation may affect stability and receptor interaction.", "mechanism": "Reduced apelin levels are associated with increased fibrosis; apelin acts as a negative regulator of fibrogenesis.", "protein": "Apelin", "relationship_type": "protective", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Primary sclerosing cholangitis (PSC)", "glycan_involvement": "AR is glycosylated; glycosylation may modulate receptor function.", "mechanism": "AR expression is upregulated by miR-125b and correlates with advanced fibrosis, especially in males.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation is essential for TGF-\u03b2 secretion and function.", "mechanism": "TGF-\u03b2 promotes fibrogenesis by activating hepatic stellate cells and ECM production.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Primary sclerosing cholangitis (PSC)", "glycan_involvement": "Glycosylation may affect apelin's half-life and receptor binding.", "mechanism": "Lower apelin levels in PSC patients are associated with increased fibrosis and disease severity.", "protein": "Apelin", "relationship_type": "protective", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 is upregulated during inflammation and promotes fibrogenesis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation required for TGF-\u03b2 maturation and secretion.", "mechanism": "Chronic overexpression of TGF-\u03b2 leads to cirrhosis via persistent fibrogenesis.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may influence AR stability and nuclear localization.", "mechanism": "AR signalling promotes fibrosis progression, especially in males with PSC.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Glycosylation is necessary for TGF-\u03b2 bioactivity.", "mechanism": "TGF-\u03b2 is upregulated in cholestatic injury, promoting inflammation and fibrosis.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12386768" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may regulate apelin's function in the liver.", "mechanism": "Reduced apelin levels are linked to progression from fibrosis to cirrhosis.", "protein": "Apelin", "relationship_type": "protective", "source_pmcid": "PMC12386768" }, { "confidence": "high", "disease": "Pompe disease (GSD II)", "glycan_involvement": "GAA is a glycoprotein; glycosylation is critical for lysosomal targeting and enzyme replacement therapy efficacy.", "mechanism": "GAA deficiency leads to lysosomal glycogen accumulation and impaired autophagy.", "protein": "Acid alpha-glucosidase (GAA)", "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "high", "disease": "Pompe disease (GSD II)", "glycan_involvement": "Recognition of mannose-6-phosphate glycans on GAA is essential for lysosomal delivery.", "mechanism": "M6PR mediates uptake of recombinant GAA in ERT.", "protein": "Mannose-6-phosphate receptor (M6PR)", "protein_enriched": { "function": "Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate rece", "gene_name": "M6PR", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G11942GC", "G92406TI", "G65953PF", "G01650EU", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G25637MV", "G39188ZX", "G62765YT", "G64527OM", "G72735IY", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G07246CJ", "G10773YW", "G10846ZT", "G13131HA", "G14547CB", "G15664MX", "G18183SM", "G20312EM", "G20706XG", "G23984SE", "G27058EU", "G27126ED", "G28541PG", "G29184RN", "G29299MO", "G30248BL", "G30970QQ", "G31028YV", "G31544HA", "G31852PQ", "G31986NC", "G33416PL", "G37692EO", "G39446WN", "G40834TG", "G41071NU", "G41840AI", "G43734MM", "G45395BF", "G46450MZ", "G46691LC", "G48414YA", "G49018RC", "G49589RB", "G49642SA", "G50282JC", "G55132BD", "G57776ZS", "G59626AS", "G59924QI", "G60834IK", "G66163OV", "G68490OW", "G68735SN", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G81124ET", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90575OW", "G90659AW", "G95133RI", "G96091TT", "G96577RX", "G99668VU", "G49108TO" ], "uniprot_id": "P20645" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386774" }, { "confidence": "high", "disease": "Cori disease (GSD III)", "glycan_involvement": "AGL is a glycoprotein involved in glycogen breakdown.", "mechanism": "AGL deficiency causes cytosolic accumulation of abnormal glycogen.", "protein": "Glycogen debranching enzyme (AGL)", "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "high", "disease": "McArdle disease (GSD V)", "glycan_involvement": "PYGM is a glycoprotein enzyme; glycosylation may affect stability/activity.", "mechanism": "PYGM deficiency impairs muscle glycogen utilization during exercise.", "protein": "Muscle glycogen phosphorylase (PYGM)", "protein_enriched": { "function": "Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular", "gene_name": "PYGM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11217" }, "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "high", "disease": "Myofibrillar myopathy (MFM6)", "glycan_involvement": "BAG3 is a glycoprotein; glycosylation may influence protein-protein interactions.", "mechanism": "BAG3 mutation impairs chaperone-assisted selective autophagy, leading to toxic protein aggregates.", "protein": "BAG3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "medium", "disease": "Myofibrillar myopathy (MFM1)", "glycan_involvement": "Desmin is glycosylated; glycosylation may affect filament assembly.", "mechanism": "Desmin mutations disrupt filament structure, causing aggregate formation and muscle fiber disintegration.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "medium", "disease": "Myofibrillar myopathy (MFM2) and Cataract", "glycan_involvement": "CRYAB is a glycoprotein; glycosylation may affect chaperone function.", "mechanism": "CRYAB mutations cause protein aggregation in muscle and lens, leading to muscle weakness and cataract.", "protein": "Alpha-crystallin B chain (CRYAB)", "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "medium", "disease": "Myofibrillar myopathy (MFM3)", "glycan_involvement": "MYOT is a glycoprotein; glycosylation may modulate interactions with other sarcomeric proteins.", "mechanism": "MYOT mutations disrupt sarcomere assembly, leading to myofibril disintegration.", "protein": "Myotilin (MYOT)", "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "medium", "disease": "Myofibrillar myopathy (MFM5)", "glycan_involvement": "FLNC is glycosylated; glycosylation may affect aggregate formation.", "mechanism": "FLNC mutations cause protein aggregation and impaired autophagy.", "protein": "Filamin C (FLNC)", "protein_enriched": { "function": "Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking prote", "gene_name": "FLNC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14315" }, "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "BAG3 glycosylation may modulate cardiac-specific interactions.", "mechanism": "BAG3 mutations disrupt proteostasis and autophagy in cardiomyocytes, leading to DCM.", "protein": "BAG3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386774" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated, which affects its processing and trafficking.", "mechanism": "Mutations increase amyloid-beta production and aggregation, leading to plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APOE is O-glycosylated; glycosylation may affect receptor binding and A\u03b2 interaction.", "mechanism": "APOE \u03b54 allele increases risk by impairing amyloid-beta clearance and modulating tau pathology.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "CLU is heavily N-glycosylated, essential for secretion and chaperone function.", "mechanism": "CLU modulates amyloid-beta clearance, neuroinflammation, and apoptosis; risk variants impair clearance.", "protein": "Clusterin (CLU)", "relationship_type": "risk/protective", "source_pmcid": "PMC12386822" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CR1 is N-glycosylated; glycosylation affects receptor stability and function.", "mechanism": "CR1 variants affect immune complex clearance and complement regulation, influencing neuroinflammation.", "protein": "Complement receptor 1 (CR1)", "protein_enriched": { "function": "Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). Mediates the bi", "gene_name": "CR1", "glycan_count": 13, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22310AV", "G40834TG", "G45395BF", "G47748JZ", "G48414YA", "G54285KU", "G57888GL", "G82830MN", "G06356OH", "G27058EU", "G79666IR", "G86795LJ", "G49108TO" ], "uniprot_id": "P17927" }, "relationship_type": "risk", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SORL1 is N-glycosylated, which is important for its trafficking and ligand binding.", "mechanism": "SORL1 regulates APP trafficking; loss leads to increased amyloidogenic processing.", "protein": "Sortilin-related receptor (SORL1/sorLA)", "relationship_type": "risk/causal", "source_pmcid": "PMC12386822" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD33 is N-glycosylated; glycosylation modulates ligand binding and signaling.", "mechanism": "CD33 modulates microglial activation and immune response, influencing amyloid clearance.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk", "source_pmcid": "PMC12386822" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is N-glycosylated, required for cell surface expression and function.", "mechanism": "TREM2 variants impair microglial response to amyloid and tau pathology.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "risk", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Mutations alter \u03b3-secretase activity, increasing toxic amyloid-beta species.", "protein": "Presenilin 1 (PSEN1)", "relationship_type": "causal", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Mutations disrupt \u03b3-secretase complex, increasing amyloid-beta production.", "protein": "Presenilin 2 (PSEN2)", "relationship_type": "causal", "source_pmcid": "PMC12386822" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation state may influence detectability and function as a biomarker.", "mechanism": "CLU levels in CSF and plasma are altered in AD; reflects amyloid and inflammatory status.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC12386822" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Reflects secretory activity and granule content of neuroendocrine tumor cells; elevated in pNETs.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "Membrane glycoprotein overexpressed in well-differentiated pNETs; enables imaging and PRRT.", "protein": "Somatostatin Receptor 2 (SSTR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "Glycosylation status not specified; nuclear localization.", "mechanism": "Proliferation marker; grading tool for tumor aggressiveness.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Loss-of-function mutations drive tumorigenesis via chromatin remodeling defects.", "protein": "MEN1 (Menin)", "protein_enriched": { "function": "Involved in microtubule stabilization in many cell types, including neuronal cells (By similarity). Specifically has microtubule cold stabilizing activity (By similarity). Involved in dendrite morphog", "gene_name": "MAP6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96JE9" }, "relationship_type": "causal", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Mutations associated with ALT phenotype and genomic instability.", "protein": "DAXX", "protein_enriched": { "function": "Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity", "gene_name": "DAXX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UER7" }, "relationship_type": "causal", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Pancreatic neuroendocrine tumor (pNET)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Mutations linked to ALT phenotype, poor prognosis, and genomic instability.", "protein": "ATRX", "protein_enriched": { "function": "Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Bi", "gene_name": "ATRX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P46100" }, "relationship_type": "causal", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Metastatic pNET", "glycan_involvement": "N-glycosylation influences secretion.", "mechanism": "Elevated plasma levels correlate with tumor burden and metastatic spread.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Metastatic pNET", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "High SSTR2 expression enables PRRT and imaging for metastatic disease.", "protein": "Somatostatin Receptor 2 (SSTR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386858" }, { "confidence": "medium", "disease": "High-grade pNET", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Elevated miR-196a2 levels associated with poor survival and aggressive disease.", "protein": "miR-196a2", "relationship_type": "biomarker", "source_pmcid": "PMC12386858" }, { "confidence": "medium", "disease": "Poorly differentiated pancreatic neuroendocrine carcinoma", "glycan_involvement": "N-glycosylation affects secretion; less relevant in poorly differentiated tumors.", "mechanism": "CgA levels may be normal or mildly elevated due to reduced granule content.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386858" }, { "confidence": "high", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation affects vWF stability and function in coagulation.", "mechanism": "Elevated vWF reflects endothelial injury and dysfunction in diabetes.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation modulates thrombomodulin's anticoagulant activity.", "mechanism": "Increased soluble thrombomodulin indicates endothelial cell damage.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "Endothelial Dysfunction", "glycan_involvement": "Selectin-ligand interactions are glycan-dependent.", "mechanism": "Selectins mediate leukocyte adhesion, upregulated in inflamed endothelium.", "protein": "Selectins", "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation influences PAI-1 secretion and stability.", "mechanism": "Elevated PAI-1 inhibits fibrinolysis, promoting thrombosis in diabetes.", "protein": "Plasminogen Activator Inhibitor-1 (PAI-1)", "protein_enriched": { "function": "Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it", "gene_name": "SERPINE1", "glycan_count": 16, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G07799LX", "G11870QZ", "G22310AV", "G26330YA", "G27058EU", "G45395BF", "G49955PK", "G51413EV", "G72791KH", "G84452RH", "G88374WZ", "G20706XG", "G92135MA", "G29068FM", "G43417UB", "G49108TO" ], "uniprot_id": "P05121" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation affects collagen assembly and ECM interactions.", "mechanism": "Excessive deposition leads to basement membrane thickening and fibrosis.", "protein": "Type IV Collagen", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386922" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation modulates t-PA activity and clearance.", "mechanism": "Altered t-PA levels reflect impaired fibrinolysis in diabetes.", "protein": "Tissue Plasminogen Activator (t-PA)", "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation regulates TGF-\u03b21 secretion and receptor binding.", "mechanism": "TGF-\u03b21 upregulation drives collagen deposition and fibrosis in diabetic heart.", "protein": "Transforming Growth Factor-beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation impacts collagen cross-linking and ECM structure.", "mechanism": "Collagen accumulation leads to cardiac scarring and dysfunction.", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC12386922" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycosylation modulates collagen's interaction with retinal cells.", "mechanism": "Basement membrane thickening contributes to retinal vascular pathology.", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC12386922" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "Glycosylation affects thrombomodulin's endothelial localization.", "mechanism": "Endothelial injury in coronary vessels increases soluble thrombomodulin.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386922" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "VWF glycosylation modulates its activity and clearance; altered glycosylation may enhance thrombosis.", "mechanism": "VWF is overexpressed in severe COVID-19, reflecting endothelial dysfunction and prothrombotic state.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects Ang1 secretion and receptor binding.", "mechanism": "Ang1 is upregulated in severe COVID-19, indicating endothelial activation and vascular dysfunction.", "protein": "Angiopoietin-1 (Ang1)", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation is critical for VEGF receptor interaction.", "mechanism": "VEGF is overexpressed in severe COVID-19, contributing to vascular permeability and inflammation.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation regulates VWF multimer size and function.", "mechanism": "Elevated VWF in COVID-19 and pregnancy increases VTE risk via enhanced platelet adhesion.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Recombinant ESAT-6 may be glycosylated to enhance immunogenicity.", "mechanism": "ESAT-6 is used in immunodiagnostic tests (e.g., Diaskintest) for TB infection.", "protein": "ESAT-6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A564" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Recombinant CFP-10 may be glycosylated for improved antigenicity.", "mechanism": "CFP-10 is used in immunodiagnostic tests for TB infection.", "protein": "CFP-10", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "D-dimer is a glycosylated fibrin degradation product.", "mechanism": "D-dimer is elevated in COVID-19 and pregnancy, indicating increased fibrinolysis and VTE risk.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "Latent tuberculosis infection", "glycan_involvement": "Glycosylation affects IFN-\u03b3 stability and receptor interaction.", "mechanism": "IFN-\u03b3 release assays (IGRA) detect TB infection by measuring IFN-\u03b3 response to TB antigens.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "medium", "disease": "Placental pathologies (e.g., intervillositis, malperfusion)", "glycan_involvement": "Altered glycosylation may affect VWF deposition in placenta.", "mechanism": "VWF overexpression in COVID-19 and TB is associated with placental vascular lesions.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "low", "disease": "Intrauterine growth restriction", "glycan_involvement": "N-glycosylation modulates Ang1 function in placental vasculature.", "mechanism": "Ang1 dysregulation in placental disease contributes to impaired fetal growth.", "protein": "Angiopoietin-1 (Ang1)", "relationship_type": "biomarker", "source_pmcid": "PMC12386941" }, { "confidence": "high", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "Nrf-2 is a glycoprotein; glycosylation may affect its stability and nuclear translocation.", "mechanism": "Upregulated in PHS liver as part of antioxidant response; T4O reduces its expression, alleviating oxidative stress.", "protein": "Nrf-2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O54968" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "Keap1 glycosylation may regulate its interaction with Nrf-2.", "mechanism": "Upregulated in PHS; regulates Nrf-2 degradation. T4O reduces Keap1 expression, modulating antioxidant response.", "protein": "Keap1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "HO-1 is a glycoprotein; glycosylation may affect its enzymatic activity.", "mechanism": "HO-1 is upregulated in PHS as a downstream antioxidant enzyme of Nrf-2; T4O reduces HO-1 expression, indicating reduced oxidative stress.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "Nrf-1 glycosylation may influence its transcriptional activity.", "mechanism": "Nrf-1 is upregulated in PHS, promoting mitochondrial biogenesis; T4O suppresses its expression, normalizing mitochondrial numbers.", "protein": "Nrf-1", "protein_enriched": { "function": "Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the co", "gene_name": "NRF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q16656" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "PGC-1\u03b1 is a glycoprotein; glycosylation may affect its coactivator function.", "mechanism": "PGC-1\u03b1 is upregulated in PHS, driving mitochondrial biogenesis; T4O reduces its expression, restoring mitochondrial homeostasis.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Pulmonary Hypertension Syndrome (PHS)", "glycan_involvement": "Tfam glycosylation may regulate its DNA binding and stability.", "mechanism": "Tfam is upregulated in PHS, enhancing mtDNA replication; T4O reduces Tfam expression, limiting excessive mitochondrial proliferation.", "protein": "Tfam", "protein_enriched": { "function": "Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193, PubMed:32183942). Component of the mitochondrial transcription initiation com", "gene_name": "TFAM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q00059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "Glycosylation may modulate Nrf-2 function in hepatocytes.", "mechanism": "Nrf-2 activation is part of the hepatic response to cirrhosis and oxidative injury in PHS.", "protein": "Nrf-2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O54968" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Oxidative Stress Injury", "glycan_involvement": "Glycosylation may affect HO-1 secretion and function.", "mechanism": "HO-1 upregulation reflects oxidative stress; its activity is protective but also a marker of injury.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Oxidative Stress Injury", "glycan_involvement": "Glycosylation may affect Nrf-2 nuclear localization.", "mechanism": "Nrf-2 activation is targeted by T4O to reduce oxidative stress in liver.", "protein": "Nrf-2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O54968" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386969" }, { "confidence": "medium", "disease": "Oxidative Stress Injury", "glycan_involvement": "Glycosylation may modulate Keap1-Nrf-2 interaction.", "mechanism": "Keap1 inhibition by T4O leads to Nrf-2 activation and reduced oxidative damage.", "protein": "Keap1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386969" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns (e.g., fucosylation) are linked to HCC progression.", "mechanism": "Elevated serum AFP is associated with tumor burden and poor prognosis in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Albumin is N-glycosylated; hypoalbuminemia may reflect altered glycosylation in liver disease.", "mechanism": "Low serum albumin reflects poor liver synthetic function and systemic inflammation, predicting worse survival.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects its stability and function in inflammation.", "mechanism": "High fibrinogen-to-albumin ratio (Fib/Alb) is associated with systemic inflammation and poor prognosis in HCC.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation; altered glycosylation may affect platelet function in liver disease.", "mechanism": "Platelet count is used in APRI and PALBI indices; thrombocytopenia reflects portal hypertension and advanced liver disease.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Immunoglobulins are heavily glycosylated; glycan changes can modulate immune response.", "mechanism": "Lymphocyte count (component of PNI) reflects immune competence; lymphopenia is linked to poor antitumor immunity.", "protein": "Immunoglobulins (lymphocyte-derived)", "relationship_type": "protective", "source_pmcid": "PMC12386984" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation of albumin is observed in cirrhosis.", "mechanism": "Hypoalbuminemia is a marker of advanced cirrhosis and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates fibrinogen's role in coagulation and inflammation.", "mechanism": "Elevated fibrinogen reflects ongoing inflammation and fibrosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycoform analysis helps distinguish HCC from benign liver disease.", "mechanism": "Mildly elevated AFP can be seen in cirrhosis, but high levels are more specific for HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation affects platelet clearance and function.", "mechanism": "Low platelet count is a surrogate for portal hypertension due to splenic sequestration.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "low", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation of immunoglobulins is associated with chronic liver disease.", "mechanism": "Reduced lymphocyte count reflects immune dysfunction in cirrhosis.", "protein": "Immunoglobulins (lymphocyte-derived)", "relationship_type": "biomarker", "source_pmcid": "PMC12386984" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "BNP and ANP are glycosylated, affecting stability and clearance.", "mechanism": "Released by cardiac stretch; levels correlate with cardiac overload and dysfunction.", "protein": "Natriuretic Peptides (BNP, NT-proBNP, ANP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "high", "disease": "Cardiac Fibrosis/Heart Failure", "glycan_involvement": "Binds \u03b2-galactoside glycans; glycan interactions mediate cell signaling and fibrosis.", "mechanism": "Promotes inflammation and fibrosis; elevated in HF, predicts mortality and rehospitalization.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "high", "disease": "Heart Failure (acute and chronic)", "glycan_involvement": "sST2 is glycosylated, which may affect its stability and receptor binding.", "mechanism": "Soluble receptor for IL-33; elevated sST2 antagonizes cardioprotective signaling, predicts mortality.", "protein": "Suppression of Tumorigenicity-2 (sST2)", "protein_enriched": { "function": "Receptor for interleukin-33 (IL-33) which plays crucial roles in innate and adaptive immunity, contributing to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RA", "gene_name": "IL1RL1", "glycan_count": 11, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22310AV", "G37881RL", "G52527GH", "G80920RR", "G84452RH", "G06356OH", "G48414YA", "G57888GL", "G82830MN", "G47748JZ", "G47518TP" ], "uniprot_id": "Q01638" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "high", "disease": "Congestive Heart Failure/Acute Heart Failure", "glycan_involvement": "Highly N- and O-glycosylated; glycan chains modulate immune response and biomarker function.", "mechanism": "Elevated in HF; reflects congestion, inflammation, and predicts mortality/readmission.", "protein": "Carbohydrate Antigen 125 (CA-125/MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Cardiac Remodeling/Heart Failure", "glycan_involvement": "Heparan sulfate glycosylation critical for cell signaling and ECM interactions.", "mechanism": "Transmembrane proteoglycan; elevated in HF, associated with LV hypertrophy and remodeling.", "protein": "Syndecan-4 (SDC-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Heart Failure/Cardiac Remodeling", "glycan_involvement": "O-glycosylation modulates cell adhesion and signaling.", "mechanism": "ECM protein upregulated by biomechanical stress; elevated in HF, predicts adverse outcomes.", "protein": "Osteopontin (OPN)", "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Chronic Heart Failure", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Neuroendocrine granule protein; increased expression correlates with HF severity and mortality.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Acute and Chronic Heart Failure", "glycan_involvement": "Glycosylation may affect peptide stability and receptor interaction.", "mechanism": "Vasodilatory hormone; MR-proADM fragment is stable and predicts mortality and hospitalization.", "protein": "Adrenomedullin (MR-proADM)", "protein_enriched": { "function": "Adrenomedullin/ADM and proadrenomedullin N-20 terminal peptide/PAMP are peptide hormones that act as potent hypotensive and vasodilatator agents (PubMed:8387282, PubMed:9620797). Numerous actions have", "gene_name": "ADM", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P35318" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Heart Failure/Cardiac Remodeling", "glycan_involvement": "Glycosylation may affect secretion and receptor binding.", "mechanism": "Stress-induced cytokine; elevated in HF, correlates with remodeling and adverse outcomes.", "protein": "Growth/Differentiation Factor 15 (GDF-15)", "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "medium", "disease": "Heart Failure/Cardiac Remodeling", "glycan_involvement": "Glycosylation modulates peptide stability and receptor interaction.", "mechanism": "Vasoconstrictor peptide; elevated in HF, promotes remodeling and inflammation.", "protein": "Endothelin-1 (ET-1)", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "EDN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P05305" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387009" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "bcf-hCG is a glycoprotein fragment derived from hCG metabolism.", "mechanism": "bcf-hCG is abundant in placenta and urine during early pregnancy; used for pregnancy diagnosis.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "Glycosylation is essential for hCG structure and function; bcf-hCG retains glycan-dependent activity.", "mechanism": "Promotes endometrial gland proliferation, thickening, and expression of implantation-supporting genes (e.g., Hoxa10), enhancing uterine receptivity and embryo implantation.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "causal", "source_pmcid": "PMC12387010" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Glycosylation affects stability and detection in clinical assays.", "mechanism": "Elevated bcf-hCG levels are associated with pre-eclampsia.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Trophoblastic neoplasms", "glycan_involvement": "Aberrant glycosylation may affect hCG isoform secretion in neoplasms.", "mechanism": "Elevated hCG and hCG-related molecules are diagnostic for trophoblastic tumors (e.g., choriocarcinoma, hydatidiform mole).", "protein": "Human chorionic gonadotropin (hCG)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387010" }, { "confidence": "medium", "disease": "Recurrent implantation failure", "glycan_involvement": "Glycosylation may influence receptor interactions and therapeutic efficacy.", "mechanism": "bcf-hCG enhances endometrial receptivity and gland proliferation, suggesting potential for improving implantation rates.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387010" }, { "confidence": "medium", "disease": "Thin endometrial lining", "glycan_involvement": "Glycan structure may modulate biological activity.", "mechanism": "bcf-hCG increases endometrial thickness and gland number, potentially treating thin endometrium.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Supports luteal function and placental development, maintaining pregnancy.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "protective", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "Glycosylation critical for hCG hormone activity and detection.", "mechanism": "hCG is a classic marker for pregnancy detection in serum and urine.", "protein": "Human chorionic gonadotropin (hCG)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01233" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387010" }, { "confidence": "medium", "disease": "Pregnancy", "glycan_involvement": "Glycosylation may affect pharmacokinetics and efficacy.", "mechanism": "Potential adjunctive treatment to improve outcomes in assisted reproductive technologies by enhancing uterine environment.", "protein": "\u03b2-core fragment hCG (bcf-hCG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Pregnancy", "glycan_involvement": "N- and O-glycosylation essential for hormone function.", "mechanism": "Induces corpus luteum to secrete progesterone, sustaining pregnancy.", "protein": "Human chorionic gonadotropin (hCG)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01233" }, "relationship_type": "causal", "source_pmcid": "PMC12387010" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "N-glycosylation modulates antigenicity and immune evasion.", "mechanism": "Persistent HBsAg exposure impairs antigen presentation and T cell activation, promoting chronic infection.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "causal", "source_pmcid": "PMC12387017" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "N-glycosylation affects secretion and immune recognition.", "mechanism": "Prolonged HBeAg exposure suppresses T cell responses, contributing to immune tolerance.", "protein": "HBeAg (Hepatitis B e antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03168" }, "relationship_type": "causal", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation regulates CD8 stability and signaling.", "mechanism": "Absolute depletion of CD8+ T cells indicates impaired antiviral immunity.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "Glycosylation modulates T cell receptor interactions.", "mechanism": "Elevated CD8+ T cell frequencies reflect ongoing immune activation.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "Glycosylation affects CD4 surface expression and function.", "mechanism": "Depletion of na\u00efve CD4+ T cells and expansion of memory subsets indicate chronic immune stimulation.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation influences receptor-ligand binding.", "mechanism": "Expansion of T follicular helper (Tfh) cells (CXCR5+) is associated with altered antibody responses.", "protein": "CXCR5", "protein_enriched": { "function": "Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph ", "gene_name": "CXCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P32302" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "Glycosylation modulates chemokine receptor trafficking.", "mechanism": "Elevated Th17 (CCR6+) cells correlate with poor clinical outcomes.", "protein": "CCR6", "protein_enriched": { "function": "Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is ", "gene_name": "CCR6", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51684" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "O-glycosylation affects isoform expression and signaling.", "mechanism": "Depletion of na\u00efve CD45RA+ T cells signals impaired immune memory formation.", "protein": "CD45RA", "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "Glycosylation critical for adhesion and migration.", "mechanism": "Redistribution of central memory (CD62L+) T cells reflects altered lymphoid homing.", "protein": "CD62L (L-selectin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation modulates chemokine responsiveness.", "mechanism": "Depletion of Tc1 (CXCR3+) cells indicates reduced antiviral cytotoxicity.", "protein": "CXCR3", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling p", "gene_name": "CXCR3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49682" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387017" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "GLP-1 is a glycoprotein hormone; glycosylation is essential for stability and secretion.", "mechanism": "GLP-1 has anti-inflammatory and cytoprotective effects; normalization of GLP-1 levels correlates with improved colitis outcomes.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 drives inflammation in IBD; reduction correlates with disease amelioration.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "IL-6 glycosylation modulates stability and activity.", "mechanism": "IL-6 is upregulated in colitis and drives inflammatory responses; suppression improves disease.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 is elevated in colitis and promotes inflammation; reduction is associated with therapeutic benefit.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "IL-17 is glycosylated, influencing its stability and immune function.", "mechanism": "IL-17 is a key driver of Th17-mediated inflammation in IBD; reduction correlates with disease improvement.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387022" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "IFN-\u03b3 glycosylation affects receptor interaction.", "mechanism": "IFN-\u03b3 is elevated in Th1-driven colitis; suppression is linked to therapeutic efficacy.", "protein": "IFN-\u03b3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "MCP-1 glycosylation modulates chemotactic activity.", "mechanism": "MCP-1 recruits monocytes to inflamed tissue; reduction limits immune cell infiltration.", "protein": "MCP-1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "MPO is glycosylated, affecting enzyme activity and localization.", "mechanism": "MPO activity reflects neutrophil infiltration and local inflammation; reduction indicates therapeutic effect.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "Colitis (DSS-induced)", "glycan_involvement": "GLP-1 glycosylation is required for proper hormone function.", "mechanism": "DSS-induced colitis disrupts GLP-1 signaling; restoration by therapy improves metabolic and inflammatory outcomes.", "protein": "GLP-1", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 bioactivity.", "mechanism": "Targeting TNF-\u03b1 with drugs or combination therapy reduces inflammation and disease severity.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387022" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N- and O-glycosylation of proteins and LacCer synthesis", "mechanism": "Overexpression correlates with tumor aggressiveness and inflammation; diagnostic and therapeutic target.", "protein": "\u03b2-1,4-Galactosyltransferase V (\u03b2-1,4-GalT-V)", "protein_enriched": { "function": "It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mann", "gene_name": "MGAT3", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ", "G43417UB", "G57321FI" ], "uniprot_id": "Q09327" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LacCer biosynthesis; N- and O-glycosylation", "mechanism": "Promotes LacCer-mediated oxidative stress and inflammation in vascular cells.", "protein": "\u03b2-1,4-Galactosyltransferase V (\u03b2-1,4-GalT-V)", "protein_enriched": { "function": "It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mann", "gene_name": "MGAT3", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ", "G43417UB", "G57321FI" ], "uniprot_id": "Q09327" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Galactosylation of Notch-1", "mechanism": "Drives trans-differentiation of glioma stem-like cells into endothelial cells via Notch-1 glycosylation, promoting angiogenesis.", "protein": "\u03b2-1,4-Galactosyltransferase V (\u03b2-1,4-GalT-V)", "protein_enriched": { "function": "It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mann", "gene_name": "MGAT3", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ", "G43417UB", "G57321FI" ], "uniprot_id": "Q09327" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "O-glycosylation (galactosylation of EGF-like repeats)", "mechanism": "Glycosylation by \u03b2-1,4-GalT-V enhances Notch-1 stability and cell surface localization, promoting tumor angiogenesis.", "protein": "Notch-1", "relationship_type": "causal", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-GlcNAcylation modulates Sp1 stability and activity", "mechanism": "Upregulates \u03b2-1,4-GalT-V and other oncogenic genes; high Sp1 linked to poor prognosis.", "protein": "Specificity Protein 1 (Sp1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Product of \u03b2-1,4-GalT-V activity", "mechanism": "Elevated LacCer induces ROS and oxidative stress, contributing to cardiac hypertrophy.", "protein": "Lactosylceramide (LacCer)", "relationship_type": "causal", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosphingolipid signaling", "mechanism": "Acts as a second messenger activating inflammatory pathways (e.g., cPLA2, prostaglandin synthesis).", "protein": "Lactosylceramide (LacCer)", "relationship_type": "causal", "source_pmcid": "PMC12387033" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "LacCer biosynthesis", "mechanism": "Dysregulation of LacCer and glycosylation contributes to diabetic complications.", "protein": "\u03b2-1,4-Galactosyltransferase V (\u03b2-1,4-GalT-V)", "protein_enriched": { "function": "It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mann", "gene_name": "MGAT3", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ", "G43417UB", "G57321FI" ], "uniprot_id": "Q09327" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "T-cell development/immune regulation", "glycan_involvement": "O-glycosylation of EGF-like repeats", "mechanism": "Glycosylation by \u03b2-1,4-GalT-V required for Notch-1 cell surface expression and T-cell differentiation.", "protein": "Notch-1", "relationship_type": "causal", "source_pmcid": "PMC12387033" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Transcriptional regulation; PD-L1 is a glycoprotein", "mechanism": "Sp1 upregulates PD-L1, promoting immune evasion in CRC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387033" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Lubricin is heavily O-glycosylated; glycosylation is essential for its lubricating function.", "mechanism": "Loss of lubricin expression in superficial cartilage layer correlates with cartilage degradation and loss of lubrication.", "protein": "Lubricin (PRG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12387052" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "CD31 is N-glycosylated; glycosylation affects cell adhesion and endothelial integrity.", "mechanism": "Reduced and irregular CD31 expression reflects microvascular compromise and ischemic zones in degenerative cartilage and bone.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "CD68 is a glycoprotein; glycosylation may affect macrophage function and antigenicity.", "mechanism": "Moderate CD68 positivity indicates chronic low-grade inflammation and correlates with tissue resorption.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "VEGF is glycosylated; glycosylation modulates receptor binding and angiogenic activity.", "mechanism": "VEGF-driven neovascularization is associated with abnormal vascularization and disease progression.", "protein": "VEGF", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "MMP-13 is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Elevated MMP-13 expression correlates with enzymatic degradation of cartilage matrix.", "protein": "MMP-13", "protein_enriched": { "function": "Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III colla", "gene_name": "MMP13", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P45452" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "ADAMTS are glycoproteins; glycosylation influences substrate specificity and activity.", "mechanism": "ADAMTS family proteases contribute to aggrecan degradation in cartilage.", "protein": "ADAMTS", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "TGF-\u03b2 is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "TGF-\u03b2 is involved in tissue remodeling and excessive vascularization.", "protein": "TGF-\u03b2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387052" }, { "confidence": "medium", "disease": "Avascular necrosis of femoral head", "glycan_involvement": "O-glycosylation is required for lubricin's protective function.", "mechanism": "Loss of lubricin in necrotic cartilage reflects impaired lubrication and tissue integrity.", "protein": "Lubricin (PRG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12387052" }, { "confidence": "high", "disease": "Avascular necrosis of femoral head", "glycan_involvement": "N-glycosylation modulates endothelial cell survival.", "mechanism": "Loss of CD31-positive vessels marks vascular infarction and bone necrosis.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387052" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "O-glycosylation is essential for lubricin's biomechanical properties.", "mechanism": "Reduced lubricin expression may contribute to increased cartilage fragility in osteoporotic bone.", "protein": "Lubricin (PRG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12387052" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Highly phosphorylated and glycosylated; glycosylation modulates ECM interactions.", "mechanism": "Promotes muscle fibrosis and fibrofatty replacement via macrophage expression; deletion reduces fibrosis and improves regeneration.", "protein": "Osteopontin", "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation critical for function in ECM remodeling.", "mechanism": "Drives ECM deposition and fibrosis in injured and dystrophic muscle.", "protein": "Osteopontin", "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Muscle regeneration", "glycan_involvement": "Glycosylation required for stability and signaling.", "mechanism": "Promotes myofiber regeneration; knockout impairs muscle repair.", "protein": "GPNMB", "relationship_type": "protective", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may regulate macrophage phenotype.", "mechanism": "Persistent GPNMB+ macrophages contribute to chronic inflammation and fibrosis.", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Macrophage-specific deletion reduces fibrosis in animal models.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "high", "disease": "Muscle regeneration", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Promotes muscle stem cell differentiation and myofiber growth.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation affects cell adhesion and signaling.", "mechanism": "Marker of scar-associated macrophages involved in ECM remodeling.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Chronic muscle inflammation", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding.", "mechanism": "Expressed by anti-inflammatory macrophages in muscle; marks M2-like state.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387070" }, { "confidence": "medium", "disease": "Muscle regeneration", "glycan_involvement": "Glycosylation may affect chemokine gradient formation.", "mechanism": "Promotes satellite cell proliferation and muscle repair.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "protective", "source_pmcid": "PMC12387070" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation required for secretion and activation.", "mechanism": "Stimulates fibrogenic cell proliferation and ECM production.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12387070" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycosylated proteins in the dystrophin-glycoprotein complex.", "mechanism": "Absence of dystrophin leads to progressive myocyte loss, increased wall stress, and cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12387109" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Complex contains glycosylated proteins essential for membrane stability and mechanotransduction.", "mechanism": "Loss of the complex impairs mechanosensing, leading to inability to compensate for biomechanical stress and cardiac remodeling.", "protein": "Dystrophin-glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12387109" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of complex components is critical for function.", "mechanism": "Defective complex disrupts mechanosensing and cardiomyocyte growth signaling, promoting cardiomyopathy.", "protein": "Dystrophin-glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12387109" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Indirect; dystrophin anchors glycoproteins at the sarcolemma.", "mechanism": "Dystrophin deficiency increases vulnerability to biomechanical stress, leading to cardiac dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12387109" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Therapeutic strategies may target glycosylation of complex components.", "mechanism": "Restoration of complex function may improve mechanosensing and cardiac outcomes.", "protein": "Dystrophin-glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387109" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Loss of glycosylation impairs complex stability.", "mechanism": "Loss of complex correlates with disease progression and severity.", "protein": "Dystrophin-glycoprotein complex", "relationship_type": "biomarker", "source_pmcid": "PMC12387109" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Restoration may re-establish glycoprotein interactions.", "mechanism": "Restoring dystrophin expression may reduce wall stress and improve cardiac function.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387109" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Target of pathogenic autoantibodies (anti-\u03b22GPI) that promote thrombosis.", "protein": "beta-2-glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387117" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycoprotein antigens; glycosylation may modulate epitope exposure.", "mechanism": "Autoantibody complex that interferes with phospholipid-binding proteins, promoting thrombosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387117" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Recognition depends on glycosylated \u03b22GPI.", "mechanism": "Autoantibody that binds cardiolipin\u2013\u03b22GPI complexes, promoting thrombosis.", "protein": "anti-cardiolipin antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387117" }, { "confidence": "high", "disease": "arterial thrombosis", "glycan_involvement": "Glycosylation modulates immunogenicity and pathogenicity.", "mechanism": "Anti-\u03b22GPI antibodies increase risk of arterial events in APS.", "protein": "beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12387117" }, { "confidence": "high", "disease": "venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation influences antibody binding and function.", "mechanism": "Anti-\u03b22GPI antibodies promote venous thrombosis in APS.", "protein": "beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12387117" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "aPL antibodies inhibit protein C, reducing anticoagulant activity.", "protein": "protein C", "relationship_type": "protective (inhibited in disease)", "source_pmcid": "PMC12387117" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation essential for activity.", "mechanism": "aPL antibodies inhibit plasminogen, impairing fibrinolysis.", "protein": "plasminogen", "relationship_type": "protective (inhibited in disease)", "source_pmcid": "PMC12387117" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects cell surface expression.", "mechanism": "aPL antibodies upregulate tissue factor, increasing thrombosis risk.", "protein": "tissue factor", "protein_enriched": { "function": "Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemosta", "gene_name": "F3", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G10486CT", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G59626AS", "G60033FS", "G27058EU" ], "uniprot_id": "P13726" }, "relationship_type": "causal", "source_pmcid": "PMC12387117" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation required for stability.", "mechanism": "aPL antibodies upregulate factor V, promoting coagulation.", "protein": "factor V", "relationship_type": "causal", "source_pmcid": "PMC12387117" }, { "confidence": "medium", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation critical for function.", "mechanism": "aPL antibodies upregulate factor VIII, enhancing thrombosis.", "protein": "factor VIII", "relationship_type": "causal", "source_pmcid": "PMC12387117" }, { "confidence": "high", "disease": "Cognitive frailty", "glycan_involvement": "FGG is a glycoprotein; glycosylation affects secretion, stability, and function in plasma.", "mechanism": "FGG levels are significantly reduced in plasma of cognitively frail elders; may reflect impaired coagulation/inflammation and systemic vulnerability.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may modulate FGG's role in tumor microenvironment and immune evasion.", "mechanism": "FGG is upregulated in urine and plasma of NSCLC patients; associated with tumor progression.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation may affect FGG's interaction with cancer cells.", "mechanism": "FGG proposed as diagnostic marker due to altered plasma levels in bladder cancer.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may influence FGG's stability and tumor association.", "mechanism": "Elevated FGG levels are related to gastric cancer progression.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may modulate FGG's role in cancer cell adhesion.", "mechanism": "Plasma FGG levels predict prostate cancer progression.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Glycosylation may affect renal filtration and FGG excretion.", "mechanism": "Urinary FGG is a non-invasive marker for mild renal fibrosis in IgAN.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation may influence FGG's inflammatory properties in lung tissue.", "mechanism": "FGG highly expressed in lung tissue of COPD patients; correlates with pulmonary function.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "Glycosylation may affect FGG's secretion and tumor association.", "mechanism": "Dysregulation of FGG expression observed in liver cancer.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "medium", "disease": "Frailty syndrome", "glycan_involvement": "Hp glycosylation modulates its antioxidant and immune functions.", "mechanism": "Hp isoforms are upregulated in plasma of frail elders.", "protein": "Haptoglobin (Hp)", "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation affects A\u03b2 aggregation and clearance.", "mechanism": "A\u03b242/A\u03b240 ratio in CSF and plasma is a reliable indicator of Alzheimer\u2019s disease.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387196" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "EPS are glycan-rich molecules interacting with host PRRs", "mechanism": "EPS modulate gut microbiota, reduce inflammation, and enhance gut barrier integrity", "protein": "Exopolysaccharides (EPS)", "relationship_type": "protective", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Irritable bowel syndrome", "glycan_involvement": "Glycosylation mediates host-pathogen recognition", "mechanism": "S-layer glycoproteins interact with dendritic cell receptors to modulate immune response", "protein": "Surface (S)-layer glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387267" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "ZO-1 is a glycoprotein essential for tight junction assembly", "mechanism": "Postbiotics upregulate ZO-1 expression, restoring tight junctions and barrier function", "protein": "Zonula occludens-1", "relationship_type": "protective", "source_pmcid": "PMC12387267" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "MUC2 is heavily O-glycosylated, critical for mucus structure", "mechanism": "Postbiotics increase MUC2 expression, enhancing mucus barrier", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "VCAM1 glycosylation modulates cell adhesion", "mechanism": "Lipoteichoic acid postbiotics reduce VCAM1 expression, decreasing leukocyte adhesion", "protein": "VCAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ICAM1 glycosylation affects leukocyte-endothelial interactions", "mechanism": "Lipoteichoic acid postbiotics reduce ICAM1 expression, limiting inflammation", "protein": "ICAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "E-selectin glycosylation is essential for ligand binding", "mechanism": "Lipoteichoic acid postbiotics downregulate E-selectin, reducing monocyte adhesion", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Claudin-1 is a glycoprotein involved in tight junctions", "mechanism": "Postbiotics upregulate claudin-1, improving tight junctions and barrier function", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "EPS glycan structure mediates immunomodulation", "mechanism": "EPS modulate gut microbiota and reduce inflammation in liver injury models", "protein": "Exopolysaccharides (EPS)", "relationship_type": "protective", "source_pmcid": "PMC12387267" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of host adhesion molecules is targeted", "mechanism": "Lipoteichoic acids reduce inflammatory adhesion molecules, protecting vasculature", "protein": "Lipoteichoic acid-associated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387267" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation affects stability and immune modulation.", "mechanism": "Central hub in complement/coagulation cascades, involved in inflammation and vascular dysfunction.", "protein": "Alpha-2-HS-glycoprotein (AHSG)", "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation modulates clot formation and immune interactions.", "mechanism": "Upregulated; promotes platelet activation, coagulation, and vascular inflammation.", "protein": "Fibrinogen alpha chain (FGA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387283" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation influences fibrin clot structure.", "mechanism": "Upregulated; involved in hemostasis and complement activation.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387283" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation critical for antibody function.", "mechanism": "Downregulated; reflects immune dysregulation and impaired humoral response.", "protein": "Immunoglobulin kappa variable 4-1 (IGKV4-1)", "protein_enriched": { "function": "V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted", "gene_name": "IGKV1-5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01602" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation modulates effector functions.", "mechanism": "Altered levels; indicates adaptive immune imbalance.", "protein": "Immunoglobulin heavy constant gamma 4 (IGHG4)", "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation required for ligand binding and cell trafficking.", "mechanism": "Upregulated; mediates leukocyte adhesion and vascular inflammation.", "protein": "Selectin-L (SELL)", "protein_enriched": { "function": "Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1281544, PubMed:1946430, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity throug", "gene_name": "ACO1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G90787TS", "G49108TO" ], "uniprot_id": "P21399" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387283" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation affects lipid binding and antioxidant activity.", "mechanism": "Downregulated; impaired HDL remodeling and lipid transport.", "protein": "Apolipoprotein A1 (APOA1)", "protein_enriched": { "function": "Glycinin is the major seed storage protein of soybean (PubMed:2485233). Glycinin basic peptides (GBPs), and, to a lower extent, glycinin exhibit antibacterial activity against Gram-negative and Gram-p", "gene_name": "GY1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04776" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation modulates receptor interactions.", "mechanism": "Downregulated; dysregulated lipid metabolism and increased renal risk.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation stabilizes enzyme activity.", "mechanism": "Downregulated; reduced antioxidant defense, increased oxidative stress.", "protein": "Paraoxonase 1 (PON1)", "protein_enriched": { "function": "Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic ", "gene_name": "PON1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G48414YA", "G49108TO", "G00912UN", "G01650EU", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G12793SR", "G15127JD", "G23294PN", "G23453IV", "G24954UD", "G26330YA", "G27947YN", "G31916IQ", "G33791AF", "G37399XV", "G40574BA", "G42358LZ", "G45395BF", "G45504EY", "G47518TP", "G52527GH", "G57776ZU", "G59626AS", "G70232NH", "G72291OX", "G75983OB", "G77547TA", "G78790NZ", "G82463GQ", "G92551JA", "G94470IW", "G95865ZB", "G99679NM", "G03644CB", "G11629QQ", "G14547CB", "G15169WU", "G23010ZW", "G43669FQ", "G56518TU", "G57776ZS", "G67164EE", "G70888PK", "G80075MS", "G85144OK", "G86880BF", "G87123QX", "G90787TS", "G93860XO", "G94917XT" ], "uniprot_id": "P27169" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387283" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation essential for protease activity and secretion.", "mechanism": "Upregulated; regulates platelet aggregation and vascular homeostasis.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387283" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and function in inflammation.", "mechanism": "Upregulated in pGDM; involved in inflammatory response and carbohydrate metabolism.", "protein": "TNFAIP6 (TSG6)", "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation may modulate anti-inflammatory activity.", "mechanism": "Upregulated in T2D; links inflammation to diabetes progression.", "protein": "TNFAIP6 (TSG6)", "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Potential glycosylation affects mitochondrial localization/function.", "mechanism": "Upregulated in pGDM; regulates glucose metabolism via pyruvate dehydrogenase inhibition.", "protein": "PDK3", "protein_enriched": { "function": "Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate d", "gene_name": "PDK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15119" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "Upregulated in T2D; may contribute to impaired glucose oxidation.", "protein": "PDK3", "protein_enriched": { "function": "Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate d", "gene_name": "PDK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15119" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "N-glycosylation modulates secretion and activity.", "mechanism": "Strongly upregulated in T2D; promotes extracellular matrix remodeling and inflammation.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387295" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Contains glycosylation-related domains; may affect protein-protein interactions.", "mechanism": "Highly upregulated in T2D; involved in apoptosis and NF-\u03baB-mediated inflammation.", "protein": "CARD6", "protein_enriched": { "function": "Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages (PubMed:11408476, Pub", "gene_name": "CARD8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2G2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "low", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Transmembrane glycoprotein; O-glycosylation affects ER function.", "mechanism": "Upregulated in T2D; involved in O-mannosylation and ER stress.", "protein": "TMTC1", "protein_enriched": { "function": "May play a role in modulation of fibrillin microfibrils in the extracellular matrix (ECM)", "gene_name": "ADAMTSL5", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "Q6ZMM2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "N-glycosylation critical for antibody function.", "mechanism": "Altered expression in pGDM; reflects immune activation.", "protein": "Immunoglobulin complex", "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "low", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation required for enzymatic activity.", "mechanism": "Most upregulated in pGDM; involved in carbohydrate digestion.", "protein": "Maltase-glucoamylase 2", "protein_enriched": { "function": "Transcription factor which acts as both an activator and a repressor (PubMed:34723967). Activates transcription of a number of genes including the heat shock chaperones HSPA1A and HSPA6 and the antiox", "gene_name": "FOXR1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PIV2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "low", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "N-glycosylation affects secretion and function.", "mechanism": "Downregulated in T2D; role in ECM remodeling.", "protein": "MMP8", "protein_enriched": { "function": "Can degrade fibrillar type I, II, and III collagens", "gene_name": "MMP8", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G08918WF", "G80075MS" ], "uniprot_id": "P22894" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387295" }, { "confidence": "high", "disease": "Optic Neuritis", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "MOG antibodies are used to rule out MOG-associated optic neuritis in differential diagnosis of optic neuropathies.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12387362" }, { "confidence": "high", "disease": "Atrophic gastritis", "glycan_involvement": "Adhesins recognize specific glycan structures on host mucins.", "mechanism": "H. pylori adhesins bind to gastric mucin glycans, facilitating colonization and chronic inflammation leading to atrophic gastritis.", "protein": "Helicobacter pylori adhesins (e.g., BabA, SabA)", "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Chronic gastritis", "glycan_involvement": "Urease is glycosylated, aiding immune evasion.", "mechanism": "Urease activity enables H. pylori survival in acidic stomach, promoting chronic inflammation.", "protein": "Helicobacter pylori urease", "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Gastric metaplasia", "glycan_involvement": "Changes in O-glycosylation patterns.", "mechanism": "Altered mucin glycosylation during H. pylori infection disrupts mucosal barrier, contributing to metaplasia.", "protein": "Mucin (MUC1, MUC5AC)", "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "MALT lymphoma", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "Chronic H. pylori infection induces IgG response, associated with MALT lymphoma development.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "Altered N-glycosylation of transferrin.", "mechanism": "H. pylori infection impairs iron absorption, reflected in altered transferrin glycoforms.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Immune thrombocytopenia", "glycan_involvement": "Glycan epitopes targeted by autoantibodies.", "mechanism": "H. pylori infection triggers autoantibodies against platelet glycoproteins.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Leptin is a glycoprotein hormone; glycosylation affects stability.", "mechanism": "H. pylori infection reduces leptin secretion, promoting hepatic lipid accumulation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "low", "disease": "NAFLD", "glycan_involvement": "Enzyme glycosylation modulates activity.", "mechanism": "H. pylori-induced inflammation upregulates stearoyl-CoA desaturase, increasing hepatic fat.", "protein": "Stearoyl-CoA desaturase", "protein_enriched": { "function": "Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates (PubMed:15907797, PubMed:18765284). Cata", "gene_name": "SCD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00767" }, "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "low", "disease": "NAFLD", "glycan_involvement": "Receptor glycosylation affects lipid uptake.", "mechanism": "H. pylori infection promotes VLDL production and hepatic lipid deposition.", "protein": "VLDL receptor", "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "medium", "disease": "Vitamin B12 deficiency", "glycan_involvement": "Intrinsic factor is a glycoprotein; glycosylation required for function.", "mechanism": "H. pylori-induced gastritis impairs intrinsic factor secretion, leading to B12 deficiency.", "protein": "Gastric intrinsic factor", "protein_enriched": { "function": "Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the CBLIF-cobalamin complex is internalized via receptor-mediated endocytosis", "gene_name": "CBLIF", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P27352" }, "relationship_type": "causal", "source_pmcid": "PMC12387484" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Rapidly increases in urine and plasma after tubular injury; predicts AKI onset, severity, and mortality.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "high", "disease": "Acute tubular injury (ATI)", "glycan_involvement": "Glycosylation facilitates renal secretion and detection in urine.", "mechanism": "Urinary NGAL levels are markedly elevated in ATI compared to HRS and prerenal AKI; distinguishes structural injury.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Transmembrane glycoprotein; glycosylation required for shedding and detection.", "mechanism": "Elevated in urine after proximal tubular injury; sensitive and specific for ischemic AKI.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation affects stability and renal filtration.", "mechanism": "Serum and urinary levels rise early in AKI; more reliable than creatinine for GFR estimation in cirrhosis.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Hepatorenal syndrome (HRS)", "glycan_involvement": "Glycosylation impacts renal handling.", "mechanism": "Elevated CysC may help identify early HRS before tubular damage occurs.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Acute tubular injury (ATI)", "glycan_involvement": "IL-18 is glycosylated for secretion.", "mechanism": "Urinary IL-18 increases after proximal tubular injury; correlates with short-term mortality.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation required for renal secretion.", "mechanism": "Urinary L-FABP predicts 3-month mortality and ACLF development in decompensated cirrhosis.", "protein": "L-FABP", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Lysosomal glycoprotein; glycosylation required for enzymatic activity.", "mechanism": "Urinary NAG increases with AKI severity; predicts short-term survival but not AKI phenotype.", "protein": "NAG", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Both are secreted glycoproteins; glycosylation required for function.", "mechanism": "Urinary levels rise in early tubular stress/cell-cycle arrest; predict AKI risk after paracentesis in cirrhosis.", "protein": "TIMP-2/IGFBP7", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "high", "disease": "Hepatorenal syndrome (HRS)", "glycan_involvement": "Glycosylation required for renal secretion.", "mechanism": "Moderately elevated in HRS; helps differentiate HRS from ATI and prerenal AKI.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12387486" }, { "confidence": "high", "disease": "Acute Heart Failure", "glycan_involvement": "NT-proBNP is N-glycosylated, which affects its stability and plasma half-life.", "mechanism": "NT-proBNP is released in response to myocardial strain and increased intracardiac pressures, reflecting neurohormonal activation in AHF.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387614" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Glycosylation modulates NT-proBNP clearance and detection.", "mechanism": "Elevated NT-proBNP correlates with increased RV-RA gradient, indicating right-sided pressure overload and pulmonary hypertension.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387614" }, { "confidence": "medium", "disease": "Right Ventricular Dysfunction", "glycan_involvement": "N-glycosylation influences NT-proBNP's circulating levels.", "mechanism": "Higher NT-proBNP levels are associated with reduced TAPSE, indicating impaired right ventricular function.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387614" }, { "confidence": "medium", "disease": "Left Ventricular Systolic Dysfunction", "glycan_involvement": "Glycosylation affects NT-proBNP's immunoreactivity and measurement.", "mechanism": "NT-proBNP increases as VTI LVOT decreases, reflecting reduced left ventricular output.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387614" }, { "confidence": "high", "disease": "In-hospital Mortality (in AHF)", "glycan_involvement": "Glycosylation impacts NT-proBNP's diagnostic accuracy.", "mechanism": "Higher NT-proBNP levels are strongly predictive of in-hospital mortality in AHF patients.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387614" }, { "confidence": "high", "disease": "Viral hepatitis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated during acute-phase response in viral hepatitis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "ApoA-I is glycosylated; glycosylation may affect HDL function.", "mechanism": "Reduced ApoA-I levels associated with greater severity and poor outcomes in liver failure.", "protein": "Apolipoprotein A-I", "relationship_type": "biomarker", "source_pmcid": "PMC12387652" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I); glycosylation modulates anti-inflammatory properties.", "mechanism": "Low HDL-C is associated with increased risk and severity of NAFLD.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "HDL glycoproteins' glycosylation influences antioxidative function.", "mechanism": "Normal HDL-C levels are associated with lower risk of cardiovascular disease.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect ApoA-I's lipid transport and anti-inflammatory roles.", "mechanism": "Reduced ApoA-I linked to NAFLD severity.", "protein": "Apolipoprotein A-I", "relationship_type": "biomarker", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "HDL-associated paraoxonase 1 inhibits LDL oxidation, reducing atherosclerosis risk.", "protein": "Paraoxonase 1", "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "HDL-associated enzyme inhibits LDL oxidation, reducing atherosclerosis risk.", "protein": "Platelet-activating factor acetylhydrolase", "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Glycosylation affects CRP's immune recognition.", "mechanism": "CRP is used as an inflammatory marker in liver dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "HDL glycoprotein glycosylation may influence anti-inflammatory effects.", "mechanism": "Low HDL-C is associated with increased risk of type 2 diabetes.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "HDL glycoprotein glycosylation may affect renal protective functions.", "mechanism": "Low HDL-C is associated with increased risk of chronic kidney disease.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12387652" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia (FH)", "glycan_involvement": "LDLR glycosylation affects receptor folding, stability, and cell surface expression.", "mechanism": "Mutations in LDLR impair LDL clearance, causing lifelong elevated LDL-C and increased ASCVD risk.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC12387733" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia (FH)", "glycan_involvement": "PCSK9 glycosylation modulates secretion and receptor interaction.", "mechanism": "Gain-of-function mutations in PCSK9 increase LDLR degradation, raising LDL-C; PCSK9 inhibitors lower LDL-C.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12387733" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia (FH)", "glycan_involvement": "ApoB glycosylation influences LDL particle structure and receptor binding.", "mechanism": "ApoB mutations reduce LDL binding to LDLR, impairing LDL clearance.", "protein": "ApoB", "relationship_type": "causal", "source_pmcid": "PMC12387733" }, { "confidence": "medium", "disease": "Familial Hypercholesterolemia (FH)", "glycan_involvement": "Glycosylation may affect adaptor protein stability and function.", "mechanism": "LDLRAP mutations disrupt LDLR internalization, leading to elevated LDL-C.", "protein": "LDLRAP", "relationship_type": "causal", "source_pmcid": "PMC12387733" }, { "confidence": "high", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation of ApoB affects LDL particle metabolism and atherogenicity.", "mechanism": "Elevated LDL particles infiltrate arterial walls, undergo oxidation, and trigger atherogenesis.", "protein": "LDL particle (ApoB-containing)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12387733" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "ApoA-I glycosylation modulates HDL function and interaction with transporters.", "mechanism": "HDL promotes reverse cholesterol transport and has anti-inflammatory effects.", "protein": "HDL (ApoA-I-containing)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12387733" }, { "confidence": "high", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation affects PCSK9 stability and receptor binding.", "mechanism": "PCSK9 inhibition increases LDLR levels, lowering LDL-C and ASCVD risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387733" }, { "confidence": "medium", "disease": "Hypertriglyceridemia/Pancreatitis", "glycan_involvement": "Glycosylation regulates ANGPTL3 secretion and activity.", "mechanism": "ANGPTL3 inhibition lowers triglycerides, reducing pancreatitis risk.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387733" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation modulates SR-BI cell surface expression and function.", "mechanism": "SR-BI mediates HDL cholesterol efflux, protecting against atherosclerosis.", "protein": "SR-BI", "relationship_type": "protective", "source_pmcid": "PMC12387733" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation affects ABCA1 trafficking and activity.", "mechanism": "ABCA1 facilitates cholesterol efflux to HDL, reducing atherogenesis.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12387733" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation affects CRP stability and clearance.", "mechanism": "Elevated CRP indicates inflammation contributing to AKI risk post-LT.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12387770" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation modulates albumin half-life and function.", "mechanism": "Hypoalbuminemia is associated with increased AKI risk after transplantation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387770" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation may affect FKBP12 interaction with tacrolimus.", "mechanism": "Tacrolimus nephrotoxicity mediated via FKBP12 increases CKD risk.", "protein": "Tacrolimus-binding protein (FKBP12)", "protein_enriched": { "function": "Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents th", "gene_name": "FKBP1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62942" }, "relationship_type": "causal", "source_pmcid": "PMC12387770" }, { "confidence": "high", "disease": "Graft Rejection", "glycan_involvement": "N-glycosylation regulates receptor expression and immune signaling.", "mechanism": "IL-2 receptor inhibition reduces acute cellular rejection post-LT.", "protein": "Interleukin-2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387770" }, { "confidence": "medium", "disease": "Graft Rejection", "glycan_involvement": "Glycosylation may influence enzyme stability.", "mechanism": "IMPDH2 inhibition suppresses lymphocyte proliferation, reducing rejection.", "protein": "Mycophenolate mofetil target (IMPDH2)", "protein_enriched": { "function": "Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays", "gene_name": "IMPDH2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12268" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387770" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation affects hemoglobin oxygen affinity.", "mechanism": "Low hemoglobin is a risk factor for poor outcomes post-LT.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387770" }, { "confidence": "medium", "disease": "Liver Transplantation Complications", "glycan_involvement": "N-glycosylation essential for prothrombin activity.", "mechanism": "Altered prothrombin levels indicate coagulation dysfunction post-LT.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387770" }, { "confidence": "high", "disease": "Hepatitis C Virus Infection", "glycan_involvement": "Heavy glycosylation shields E2 from immune detection.", "mechanism": "E2 mediates viral entry and immune evasion, increasing AKI risk.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "causal", "source_pmcid": "PMC12387770" }, { "confidence": "low", "disease": "Post-reperfusion Syndrome", "glycan_involvement": "Glycosylation affects transporter localization and function.", "mechanism": "Norepinephrine infusion mitigates hypotension and reduces AKI risk.", "protein": "Norepinephrine transporter (SLC6A2)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, P", "gene_name": "SLC6A2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P23975" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387770" }, { "confidence": "low", "disease": "Liver Transplantation Complications", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated AST indicates graft injury and risk of complications.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12387770" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects antibody function and CNS trafficking.", "mechanism": "Elevated intrathecal anti-A. muciniphila IgG correlates with increased brain lesion load and CSF immune cell infiltration.", "protein": "Anti-Akkermansia muciniphila IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Bacterial glycoproteins degrade host mucin O-glycans, impacting barrier integrity.", "mechanism": "Mucin-degrading activity reduces mucus thickness, promoting gut barrier dysfunction and bacterial translocation.", "protein": "Akkermansia muciniphila mucin-degrading glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "Elevated intrathecal IgG against gut bacteria suggests leaky gut and immune activation in MS.", "protein": "Anti-P. melaninogenica IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "IgG glycosylation influences CNS entry and effector function.", "mechanism": "Increased intrathecal IgG against E. coli indicates gut-derived immune activation in MS.", "protein": "Anti-E. coli IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "IgG glycosylation affects antibody-mediated inflammation.", "mechanism": "Elevated anti-B. fragilis IgG in CSF reflects gut barrier dysfunction and immune activation.", "protein": "Anti-B. fragilis IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "NF-L is glycosylated; glycosylation may affect stability and detection.", "mechanism": "NF-L is a marker of neuroaxonal damage; levels do not correlate with anti-A. muciniphila IgG.", "protein": "Neurofilament light chain (NF-L)", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "CHI3L1 is glycosylated; glycosylation influences secretion and activity.", "mechanism": "CHI3L1 is a marker of CNS inflammation; levels do not correlate with anti-A. muciniphila IgG.", "protein": "Chitinase 3-like 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Leaky Gut Syndrome", "glycan_involvement": "IgG glycosylation modulates immune response to translocated bacteria.", "mechanism": "Elevated anti-A. muciniphila IgG reflects increased gut permeability and bacterial translocation.", "protein": "Anti-Akkermansia muciniphila IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Leaky Gut Syndrome", "glycan_involvement": "O-glycan cleavage from host mucins by bacterial enzymes.", "mechanism": "Mucin degradation by bacterial glycoproteins leads to reduced mucus barrier and increased permeability.", "protein": "Akkermansia muciniphila mucin-degrading glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12387791" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "IgG glycosylation may affect pathogenicity in CNS autoimmunity models.", "mechanism": "Transfer of gut microbiota from MS patients (with high anti-A. muciniphila IgG) exacerbates EAE in mice.", "protein": "Anti-Akkermansia muciniphila IgG", "relationship_type": "causal", "source_pmcid": "PMC12387791" }, { "confidence": "high", "disease": "MACE", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation modulates its stability and function in coagulation.", "mechanism": "Elevated fibrinogen reflects increased coagulation and inflammation, associated with higher risk of postoperative complications.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation affects fibrinogen\u2019s inflammatory properties.", "mechanism": "High fibrinogen levels linked to increased risk of postoperative renal impairment.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "MACE", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation affects anti-inflammatory and antioxidant functions.", "mechanism": "Lower HDL levels associated with increased risk of adverse cardiac events; paradoxical associations noted in surgical context.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "MACE", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Preoperative anemia (low hemoglobin) increases risk of postoperative complications including MACE.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "low", "disease": "MACE", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIIb/IIIa) are N-glycosylated, affecting aggregation.", "mechanism": "Platelet count and function (mediated by glycoproteins) contribute to thrombotic risk post-surgery.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "high", "disease": "MACE", "glycan_involvement": "ECM glycoproteins (e.g., collagen, laminin) are glycosylated, influencing valve structure and function.", "mechanism": "Altered mitral annular geometry (reflecting ECM glycoprotein remodeling) is a strong predictor of MACE.", "protein": "Mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "MACE", "glycan_involvement": "Glycosylation of ECM proteins maintains valve integrity.", "mechanism": "Larger tricuspid annular area (reflecting healthy ECM glycoprotein composition) is protective against MACE.", "protein": "Tricuspid valve glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation modulates fibrinogen\u2019s role in clot formation.", "mechanism": "Elevated fibrinogen increases risk of thromboembolic events such as stroke post-surgery.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Glycosylation affects fibrinogen\u2019s pro-thrombotic activity.", "mechanism": "High fibrinogen levels associated with increased risk of perioperative MI.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "low", "disease": "Postoperative Atrial Fibrillation (POAF)", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-inflammatory properties.", "mechanism": "Low HDL may contribute to increased risk of POAF via reduced anti-inflammatory effects.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387864" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "BNP is a glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "BNP is elevated in AF due to atrial stretch and remodeling.", "protein": "B-type natriuretic peptide", "relationship_type": "biomarker", "source_pmcid": "PMC12387906" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation modulates BNP half-life and bioactivity.", "mechanism": "Elevated BNP is associated with increased risk of cardioembolic stroke in AF.", "protein": "B-type natriuretic peptide", "relationship_type": "biomarker", "source_pmcid": "PMC12387906" }, { "confidence": "high", "disease": "portal hypertension", "glycan_involvement": "vWF is a heavily glycosylated plasma glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated vWF levels correlate with severity and predict decompensation/mortality in portal hypertension.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12387944" }, { "confidence": "high", "disease": "liver cirrhosis", "glycan_involvement": "sVCAM-1 is N-glycosylated; glycosylation modulates its cell adhesion properties.", "mechanism": "Serum sVCAM-1 reflects endothelial dysfunction and correlates with portal pressure changes after NSBB therapy.", "protein": "soluble vascular cell adhesion molecule-1 (sVCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12387944" }, { "confidence": "high", "disease": "hepatic fibrosis", "glycan_involvement": "ICAM-1 is N-glycosylated; glycosylation is essential for its cell surface expression and function.", "mechanism": "ICAM-1 on HSCs mediates ferritin-induced NLRP3 inflammasome activation, promoting fibrosis.", "protein": "intercellular adhesion molecule-1 (ICAM-1)", "relationship_type": "causal", "source_pmcid": "PMC12387944" }, { "confidence": "medium", "disease": "portal hypertension", "glycan_involvement": "Not specified.", "mechanism": "High \u03b2-arrestin-2 expression predicts better NSBB response and longer variceal bleeding-free interval.", "protein": "beta-arrestin-2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12387944" }, { "confidence": "medium", "disease": "portal hypertension", "glycan_involvement": "Not specified.", "mechanism": "ET-1 increases intrahepatic vascular resistance, contributing to portal hypertension.", "protein": "endothelin-1 (ET-1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387944" }, { "confidence": "medium", "disease": "hepatic fibrosis", "glycan_involvement": "TGF-\u03b2 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "TGF-\u03b2 promotes HSC activation and myofibroblast differentiation, driving fibrosis.", "protein": "transforming growth factor-beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12387944" }, { "confidence": "high", "disease": "portal hypertension", "glycan_involvement": "GPCRs are often glycosylated, affecting trafficking and ligand binding; specific sites not detailed.", "mechanism": "\u03b23-AR agonists induce NO-mediated vasodilation, lowering portal pressure without cardiac compromise.", "protein": "beta-3 adrenergic receptor (\u03b23-AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis", "gene_name": "ADRB3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P13945" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387944" }, { "confidence": "medium", "disease": "hepatic fibrosis", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect stability and immune recognition.", "mechanism": "FTH activates NLRP3 inflammasome via ICAM-1, increasing IL-1\u03b2 and promoting fibrosis.", "protein": "ferritin heavy chain (FTH)", "relationship_type": "causal", "source_pmcid": "PMC12387944" }, { "confidence": "medium", "disease": "ascites", "glycan_involvement": "Not applicable.", "mechanism": "Elevated miR-181b-5p at 1 year predicts ascites development in cirrhosis.", "protein": "microRNA-181b-5p (miR-181b-5p)", "relationship_type": "biomarker", "source_pmcid": "PMC12387944" }, { "confidence": "high", "disease": "endothelial dysfunction", "glycan_involvement": "N-glycosylation modulates sVCAM-1 function.", "mechanism": "High sVCAM-1 levels indicate systemic inflammation and endothelial dysfunction in cirrhosis.", "protein": "soluble vascular cell adhesion molecule-1 (sVCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12387944" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation affects APP trafficking and processing.", "mechanism": "APP is cleaved to produce A\u03b2 peptides, which aggregate into amyloid plaques, a hallmark of AD.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation modulates BACE1 stability and localization.", "mechanism": "BACE1 cleaves APP to generate A\u03b2; increased BACE1 activity correlates with elevated A\u03b2 in AD.", "protein": "BACE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "O-glycosylation may modulate tau aggregation (not detailed in article).", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles; CSF p-tau217 and p-tau231 are early AD biomarkers.", "protein": "Tau (MAPT)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation affects APOE isoform function and receptor binding.", "mechanism": "APOE \u03b54 allele increases AD risk and modulates amyloid deposition.", "protein": "APOE", "relationship_type": "genetic risk factor", "source_pmcid": "PMC12388077" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "Plasma GFAP levels correlate with amyloid pathology and cognitive decline.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388077" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "CSF NRGN levels decrease with AD progression.", "protein": "NRGN", "relationship_type": "biomarker", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Methylation/glycosylation may regulate PP2A activity (not detailed in article).", "mechanism": "PP2A dephosphorylates tau; its dysfunction leads to tau hyperphosphorylation and neurodegeneration.", "protein": "PP2A", "relationship_type": "causal/protective", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "GSK3\u03b2 hyperactivity promotes tau phosphorylation, amyloidogenesis, and neuroinflammation.", "protein": "GSK3\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "Cdk5 hyperactivation (via p25) induces tau phosphorylation and A\u03b2 production.", "protein": "Cdk5", "relationship_type": "causal", "source_pmcid": "PMC12388077" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "Hyperphosphorylated CRMP2 found in AD brains and tangles; early marker of pathology.", "protein": "CRMP2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388077" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Cell surface glycoproteins mediate immune interactions and migration.", "mechanism": "Elevated neutrophil count reflects systemic inflammation and is associated with increased mortality and complications in T2DM.", "protein": "Neutrophil", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycoproteins on monocyte surface facilitate adhesion and transmigration.", "mechanism": "Monocytosis is linked to severity of diabetic retinopathy, indicating inflammatory damage.", "protein": "Monocyte", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation affects lymphocyte receptor function and immune modulation.", "mechanism": "Low lymphocyte counts (as part of NLR, LMR) are associated with higher cardiovascular risk and mortality.", "protein": "Lymphocyte", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Platelet glycoproteins mediate aggregation and vascular inflammation.", "mechanism": "Platelet-to-lymphocyte ratio (PLR) and SII index involving platelets are linked to macrovascular complications.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP indicates systemic inflammation and predicts vascular complications in T2DM.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and signaling.", "mechanism": "IL-6 disrupts insulin signaling and promotes beta-cell apoptosis, contributing to T2DM pathogenesis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion and activity.", "mechanism": "TNF-\u03b1 induces insulin resistance and beta-cell dysfunction.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects IL-1\u03b2 stability and receptor interaction.", "mechanism": "IL-1\u03b2 promotes beta-cell apoptosis and impairs insulin secretion.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "causal", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Non-enzymatic glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "Elevated HbA1c is associated with increased risk of microvascular complications including nephropathy.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Glycoprotein-mediated immune activation and inflammation.", "mechanism": "High neutrophil-to-lymphocyte ratio (NLR) predicts increased all-cause mortality in T2DM.", "protein": "Neutrophil", "relationship_type": "biomarker", "source_pmcid": "PMC12388079" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields epitopes, modulates infectivity and immune evasion.", "mechanism": "S protein mediates viral entry via ACE2 receptor binding.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12388196" }, { "confidence": "medium", "disease": "Long COVID (PASC)", "glycan_involvement": "Glycosylation may affect immune recognition and persistence.", "mechanism": "Persistent S protein may contribute to post-acute sequelae.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation required for receptor binding.", "mechanism": "HE facilitates viral attachment and entry in some betacoronaviruses.", "protein": "Hemagglutinin-Esterase (HE) glycoprotein", "protein_enriched": { "function": "S1 region attaches the virion to the cell membrane by interacting with host ACE2, initiating the infection (PubMed:15897467, PubMed:19901337, PubMed:29142129). Binding to the receptor probably induces", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 32, "glytoucan_ids": [], "uniprot_id": "Q6Q1S2" }, "relationship_type": "causal", "source_pmcid": "PMC12388196" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "E protein used in diagnostic assays for viral detection.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence virion assembly.", "mechanism": "M protein used in diagnostic assays for viral detection.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Potential O-glycosylation may affect immunogenicity.", "mechanism": "N protein is a major target in antigen tests.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects aggregation and detection.", "mechanism": "Aptamer-based assays detect amyloid-beta as a diagnostic marker.", "protein": "Amyloid-beta", "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation.", "mechanism": "Aptamer-based assays detect tau protein for diagnosis.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation affects PSA detection and specificity.", "mechanism": "Aptamer-based assays detect PSA for cancer diagnosis.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "medium", "disease": "Oncological complications", "glycan_involvement": "Glycosylation patterns distinguish tumor-derived exosomes.", "mechanism": "Aptamer-based assays detect exosomal glycoproteins for cancer monitoring.", "protein": "Exosomal glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388196" }, { "confidence": "high", "disease": "Hemolytic anemia", "glycan_involvement": "LAC targets glycoprotein complexes (e.g., \u03b22 glycoprotein I) on cell surfaces, affecting immune recognition.", "mechanism": "LAC positivity is independently associated with increased risk of autoimmune hemolytic anemia in APS, possibly via complement activation or Fc receptor-mediated clearance of erythrocytes.", "protein": "Lupus anticoagulant (LAC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388202" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "\u03b22 glycoprotein I is heavily glycosylated; glycan structures influence antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against \u03b22 glycoprotein I are central to APS pathogenesis, mediating thrombosis and immune dysregulation.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Hemolytic anemia", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may modulate immune recognition.", "mechanism": "Anticardiolipin IgG positivity is associated with hemolytic anemia in APS (univariate analysis), but not independently in multivariate analysis.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "LAC interacts with glycoprotein complexes on platelets, affecting immune-mediated clearance.", "mechanism": "LAC positivity is associated with thrombocytopenia in APS, though not independently in multivariate analysis.", "protein": "Lupus anticoagulant (LAC)", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Hemolytic anemia", "glycan_involvement": "Glycosylation of \u03b22 glycoprotein I affects autoantibody binding and immune activation.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are present in APS patients with hemolytic anemia, suggesting a role in immune-mediated red cell destruction.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation modulates antigenicity.", "mechanism": "LAC is a diagnostic marker and pathogenic factor in APS, associated with both thrombotic and non-thrombotic manifestations.", "protein": "Lupus anticoagulant (LAC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388202" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Recognizes glycoprotein-phospholipid complexes; glycan structures influence immune response.", "mechanism": "Anticardiolipin antibodies are diagnostic markers for APS and contribute to disease pathogenesis.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation affects antibody binding and platelet clearance.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are associated with thrombocytopenia in APS.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Targets glycoprotein complexes; glycosylation may modulate immune interactions.", "mechanism": "LAC positivity is common in SLE and associated with increased risk of APS-related hematologic manifestations.", "protein": "Lupus anticoagulant (LAC)", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation influences antigenicity and immune response.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are frequently detected in SLE patients with APS features.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12388202" }, { "confidence": "high", "disease": "Chagas disease", "glycan_involvement": "O-glycosylation critical for mucin-mediated adhesion.", "mechanism": "Facilitate adhesion of T. cruzi epimastigotes to rectal cuticle, promoting metacyclogenesis and transmission.", "protein": "Gp35/50 kDa mucins", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "medium", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Mannose/glucose-rich N-glycans mediate parasite-vector interactions.", "mechanism": "Involved in immune modulation, cell adhesion, and parasite colonization in the triatomine gut.", "protein": "ConA-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "medium", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "N-acetylglucosamine/sialic acid residues recognized by WGA.", "mechanism": "Implicated in host\u2013parasite interactions, possibly mediating parasite adhesion or immune evasion.", "protein": "WGA-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "medium", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Gal\u03b21-3GalNAc O-glycans mediate parasite adhesion.", "mechanism": "Facilitate T. cruzi attachment and establishment in the rectum, influencing metacyclogenesis.", "protein": "PNA-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "low", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Glycosylation status may affect stability/function.", "mechanism": "Loss in infected RE suggests these proteins may have protective roles against infection.", "protein": "Low molecular weight glycoproteins (<25 kDa)", "relationship_type": "protective", "source_pmcid": "PMC12388207" }, { "confidence": "low", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Likely N- or O-glycosylated; details unknown.", "mechanism": "Conserved proteins possibly essential for gut function and parasite development.", "protein": "High molecular weight glycoproteins (40, 50, 114, 248 kDa)", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Post-translational glycosylation modulates function.", "mechanism": "Differential expression correlates with higher metacyclogenesis index in females.", "protein": "Metacyclogenesis-associated glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12388207" }, { "confidence": "medium", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "O-glycosylation mediates mucin function.", "mechanism": "Support parasite survival and differentiation in the rectum.", "protein": "Triatomine gut mucins (unspecified)", "relationship_type": "causal", "source_pmcid": "PMC12388207" }, { "confidence": "low", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Not specified.", "mechanism": "Involved in muscle contraction and excretion, possibly affecting parasite release.", "protein": "Locustatachykinin I/II", "relationship_type": "biomarker", "source_pmcid": "PMC12388207" }, { "confidence": "low", "disease": "Trypanosoma cruzi infection", "glycan_involvement": "Not specified.", "mechanism": "Inhibits muscle contraction in the rectum, potentially modulating parasite excretion.", "protein": "Allatostatin", "relationship_type": "biomarker", "source_pmcid": "PMC12388207" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation critical for host-pathogen interaction and immune evasion", "mechanism": "gp60 mediates host cell attachment and invasion; subtype IIcA5G3 linked to anthroponotic transmission in AIDS patients", "protein": "gp60 glycoprotein (Cryptosporidium parvum)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth o", "gene_name": "RLN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04808" }, "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation facilitates mucosal colonization", "mechanism": "gp60 subtype IfA12G1R5 associated with sporadic outbreaks in immunocompromised hosts", "protein": "gp60 glycoprotein (Cryptosporidium hominis)", "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "O-glycosylation enables cross-species infectivity", "mechanism": "gp60 subtype IIIbA22G1R1c linked to zoonotic transmission from poultry to humans", "protein": "gp60 glycoprotein (Cryptosporidium meleagridis)", "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "Diarrhea in AIDS patients", "glycan_involvement": "Glycosylation status may influence severity of infection", "mechanism": "Presence of gp60 subtype IIcA5G3 correlates with diarrheal symptoms in immunodeficient patients", "protein": "gp60 glycoprotein (Cryptosporidium parvum)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth o", "gene_name": "RLN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04808" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "Giardiasis", "glycan_involvement": "Glycosylation required for cyst formation and environmental survival", "mechanism": "\u03b2-giardin is a structural glycoprotein essential for cyst wall integrity and infectivity", "protein": "\u03b2-giardin (Giardia duodenalis)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth o", "gene_name": "RLN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04090" }, "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "medium", "disease": "Diarrhea in AIDS patients", "glycan_involvement": "Glycosylation may affect immune recognition", "mechanism": "Detection of \u03b2-giardin gene in stool correlates with symptomatic giardiasis in immunocompromised hosts", "protein": "\u03b2-giardin (Giardia duodenalis)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth o", "gene_name": "RLN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04090" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Glycosylation aids immune evasion in immunodeficient hosts", "mechanism": "gp60 subtype IIcA5G3 preferentially infects HIV-positive individuals due to compromised immunity", "protein": "gp60 glycoprotein (Cryptosporidium parvum)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth o", "gene_name": "RLN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04808" }, "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Glycosylation supports cross-species transmission", "mechanism": "Zoonotic transmission of gp60 subtype IIIbA22G1R1c observed in AIDS patients", "protein": "gp60 glycoprotein (Cryptosporidium meleagridis)", "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycosylation may facilitate adaptation to new hosts", "mechanism": "Assemblage E \u03b2-giardin linked to zoonotic transmission from livestock to humans", "protein": "\u03b2-giardin (Giardia duodenalis, assemblage E)", "relationship_type": "causal", "source_pmcid": "PMC12388234" }, { "confidence": "medium", "disease": "Diarrhea in AIDS patients", "glycan_involvement": "Glycosylation influences pathogenicity", "mechanism": "Subtype IfA12G1R5 associated with diarrheal outbreaks in immunocompromised populations", "protein": "gp60 glycoprotein (Cryptosporidium hominis)", "relationship_type": "biomarker", "source_pmcid": "PMC12388234" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Extensive glycosylation masks epitopes, impairs antibody recognition.", "mechanism": "Mediates viral attachment to host cells and immune evasion via glycan shield and CX3C motif.", "protein": "RSV G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Mediates viral fusion and entry; main target for neutralizing antibodies.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation supports immune evasion and receptor mimicry.", "mechanism": "CX3C motif mimics fractalkine, binds CX3CR1, skews immune response to Th2, increases inflammation.", "protein": "RSV G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12388328" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation enables immune modulation and chronic sequelae.", "mechanism": "Early-life RSV G-driven Th2/Th17 skewing and airway injury linked to later asthma.", "protein": "RSV G glycoprotein", "relationship_type": "causal/risk factor", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Glycosylation enhances decoy function.", "mechanism": "Acts as decoy, binds neutralizing antibodies, reduces effective humoral response.", "protein": "Secreted G glycoprotein", "relationship_type": "immune evasion", "source_pmcid": "PMC12388328" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation modulates TLR4 interaction.", "mechanism": "F protein triggers TLR4, induces inflammation, contributes to airway injury.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Fc glycosylation affects placental transfer and effector function.", "mechanism": "Maternal and vaccine-induced IgG neutralizes F and G proteins, prevents infection.", "protein": "IgG (neutralizing antibody)", "relationship_type": "protective", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Antibody glycosylation affects half-life and efficacy.", "mechanism": "Monoclonal antibody binds F protein, prevents viral entry, reduces hospitalization.", "protein": "Palivizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Fc glycan engineering extends half-life.", "mechanism": "Long-acting monoclonal antibody targets prefusion F protein, provides seasonal protection.", "protein": "Nirsevimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388328" }, { "confidence": "medium", "disease": "Recurrent wheezing", "glycan_involvement": "Glycosylation supports immune evasion and chronic inflammation.", "mechanism": "G protein-driven immune modulation and airway injury in infancy linked to later wheezing.", "protein": "RSV G glycoprotein", "relationship_type": "risk factor", "source_pmcid": "PMC12388328" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation (isomerization) increases with fibrosis progression.", "mechanism": "Serum M2BPGi levels correlate with fibrosis severity; reflects glycosylation changes in liver disease.", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects stability and secretion; involved in ECM remodeling.", "mechanism": "Serum CHI3L1 levels correlate positively with histological severity of fibrosis.", "protein": "Chitinase 3-like 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "AFP is N-glycosylated; glycan changes may affect detection and function.", "mechanism": "Serum AFP increases in chronic hepatitis and cirrhosis; used in diagnostic panels.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "HA is a glycosaminoglycan; accumulation reflects ECM remodeling.", "mechanism": "Serum HA levels increase with fibrosis due to impaired clearance and increased synthesis.", "protein": "Hyaluronan (HA)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect peptide stability and clearance.", "mechanism": "Serum PIIINP reflects collagen turnover and fibrosis progression.", "protein": "Procollagen type III N-terminal peptide (PIIINP)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Collagen IV is glycosylated; glycan changes may reflect disease state.", "mechanism": "Serum IVC increases with fibrosis due to ECM deposition.", "protein": "Type IV collagen (IVC)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Laminin is heavily glycosylated; glycan changes affect ECM interactions.", "mechanism": "Serum LN increases with fibrosis due to basement membrane remodeling.", "protein": "Laminin (LN)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "PTX3 is glycosylated; glycan status may affect immune function.", "mechanism": "PTX3 levels decrease in CHB and further with fibrosis progression; involved in inflammation and tissue repair.", "protein": "Pentraxin-3 (PTX3)", "protein_enriched": { "function": "Plays a role in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility", "gene_name": "PTX3", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G33609NS", "G39446WN", "G45395BF", "G80920RR", "G43417UB" ], "uniprot_id": "P26022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "ACE is N-glycosylated; glycosylation may affect activity and clearance.", "mechanism": "Serum ACE levels increase with advanced fibrosis; reflects hepatic endothelial dysfunction.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "BChE is N-glycosylated; glycan changes may affect serum levels.", "mechanism": "Serum BChE decreases in cirrhosis due to reduced hepatic synthesis.", "protein": "Butyrylcholinesterase (BChE)", "relationship_type": "biomarker", "source_pmcid": "PMC12388333" }, { "confidence": "high", "disease": "Burning Mouth Syndrome (BMS)", "glycan_involvement": "N-glycosylation affects IgA stability and mucosal immune function.", "mechanism": "Elevated salivary IgA correlates with psychological stress and immune activation in BMS.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "high", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "N-glycosylation modulates IL-6 secretion and receptor binding.", "mechanism": "Elevated IL-6 in saliva and tissue reflects active inflammation and disease severity in OLP.", "protein": "Interleukin 6 (IL-6)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "high", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "N-glycosylation influences IL-8 chemotactic activity.", "mechanism": "Higher salivary and serum IL-8 levels are associated with OLP, especially erosive forms.", "protein": "Interleukin 8 (IL-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "high", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 receptor interactions.", "mechanism": "TNF-\u03b1 mediates keratinocyte apoptosis and chronic mucosal inflammation in OLP.", "protein": "Tumor Necrosis Factor alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12388356" }, { "confidence": "medium", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "N-glycosylation affects IL-17 stability and immune signaling.", "mechanism": "IL-17 is elevated in erosive OLP, promoting Th17-driven inflammation.", "protein": "Interleukin 17 (IL-17)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "medium", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "N-glycosylation modulates IL-23 secretion.", "mechanism": "IL-23 supports Th17 cell expansion and chronic inflammation in OLP.", "protein": "Interleukin 23 (IL-23)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "medium", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "Glycosylation influences MMP-9 enzymatic activity.", "mechanism": "Elevated MMP-9 in saliva is linked to tissue remodeling and lesion severity in OLP.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "medium", "disease": "Burning Mouth Syndrome (BMS)", "glycan_involvement": "N-glycosylation is essential for CBG function and cortisol transport.", "mechanism": "Altered CBG may affect free cortisol levels and stress response in BMS.", "protein": "Cortisol-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12388356" }, { "confidence": "high", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "Glycosylation modulates antigen presentation efficiency.", "mechanism": "Upregulated MHC II on APCs drives T-cell activation and autoimmunity in OLP.", "protein": "Major Histocompatibility Complex class II (MHC II)", "relationship_type": "causal", "source_pmcid": "PMC12388356" }, { "confidence": "medium", "disease": "Oral Lichen Planus (OLP)", "glycan_involvement": "Glycosylation affects FasL receptor binding and apoptotic signaling.", "mechanism": "FasL induces keratinocyte apoptosis via Fas signaling in OLP lesions.", "protein": "Fas Ligand (FasL)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-m", "gene_name": "FASLG", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48023" }, "relationship_type": "causal", "source_pmcid": "PMC12388356" }, { "confidence": "high", "disease": "IBV intestinal disease", "glycan_involvement": "S2 is a glycoprotein; glycosylation may affect fusion and tropism, but specific glycan sites not detailed.", "mechanism": "S2 subunit is necessary and sufficient for high-titer viral replication in the duodenum, conferring intestinal tropism.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "causal", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "Duodenal epithelial inflammation", "glycan_involvement": "Glycosylation may modulate immune recognition and fusion efficiency.", "mechanism": "S2-driven replication triggers upregulation of pro-inflammatory cytokines (IL-6, IL-17A, IL-22, TNF-\u03b1, IFN-\u03b2, IFN-\u03b3).", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "causal", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "Disrupted intestinal barrier integrity", "glycan_involvement": "Glycosylation could affect S2 structure and interaction with host membranes.", "mechanism": "S2 subunit suppresses tight junction proteins (Occludin, Claudin-1, ZO-1), compromising barrier function.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "causal", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "IBV intestinal disease", "glycan_involvement": "Targeting glycosylated S2 may enhance vaccine efficacy.", "mechanism": "S2 identified as a prime molecular target for vaccine development against intestinal IBV pathotypes.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "IBV nephritis", "glycan_involvement": "Not involved in renal tropism.", "mechanism": "Renal tropism is independent of S2 subunit; S2 does not confer nephropathogenicity.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "no causal relationship", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "IBV intestinal disease", "glycan_involvement": "S1 glycosylation not implicated in enteric tropism in this study.", "mechanism": "S1 subunit alone does not confer duodenal tropism or pathology.", "protein": "Spike glycoprotein S1 subunit", "relationship_type": "no causal relationship", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "IBV respiratory and renal disease", "glycan_involvement": "S1 glycosylation may affect receptor binding specificity.", "mechanism": "S1 subunit polymorphisms drive receptor binding and tropism for respiratory and renal tissues.", "protein": "Spike glycoprotein S1 subunit", "relationship_type": "causal", "source_pmcid": "PMC12388379" }, { "confidence": "medium", "disease": "IBV intestinal disease", "glycan_involvement": "Glycosylation status may be used for strain identification.", "mechanism": "Presence of CSL-S2 in viral genome is a biomarker for duodenal tropism.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "biomarker", "source_pmcid": "PMC12388379" }, { "confidence": "medium", "disease": "IBV intestinal disease", "glycan_involvement": "Glycosylation may modulate S2\u2019s fusion activity and protease sensitivity.", "mechanism": "S2 adaptation to duodenal microenvironment (pH, proteases) facilitates efficient viral entry and replication.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "causal", "source_pmcid": "PMC12388379" }, { "confidence": "medium", "disease": "IBV intestinal disease", "glycan_involvement": "Glycosylation may enhance immunogenicity.", "mechanism": "S2 elicits robust cross-protective immunity, suggesting vaccine potential.", "protein": "Spike glycoprotein S2 subunit", "relationship_type": "protective", "source_pmcid": "PMC12388379" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects membrane localization and stability.", "mechanism": "Inhibition by digoxin increases intracellular Ca2+, enhancing contractility.", "protein": "Na+/K+-ATPase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388402" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and is correlated with digoxin levels.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388402" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation regulates trafficking and drug transport activity.", "mechanism": "P-gp modulates digoxin clearance; inhibition increases toxicity risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation influences enzyme function.", "mechanism": "Digoxin slows ventricular rate via Na+/K+-ATPase inhibition.", "protein": "Na+/K+-ATPase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Ventricular Tachycardia/Fibrillation", "glycan_involvement": "Glycosylation may affect susceptibility to inhibition.", "mechanism": "Digoxin toxicity can induce arrhythmias via altered ion gradients.", "protein": "Na+/K+-ATPase", "relationship_type": "causal", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Liver Failure", "glycan_involvement": "Glycosylation affects hepatic expression and function.", "mechanism": "Impaired hepatic metabolism and P-gp inhibition elevate digoxin levels.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation modulates pump activity.", "mechanism": "SERCA regulates Ca2+ reuptake; dysfunction contributes to contractile impairment.", "protein": "SERCA (ATP2A2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation influences channel gating.", "mechanism": "RyR2 dysfunction disrupts Ca2+ release, worsening heart failure.", "protein": "Ryanodine receptor 2 (RyR2)", "protein_enriched": { "function": "Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. ", "gene_name": "RYR2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G90039BC" ], "uniprot_id": "Q92736" }, "relationship_type": "causal", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Multi-Organ Failure", "glycan_involvement": "Glycosylation essential for stability in circulation.", "mechanism": "NT-proBNP levels rise with worsening cardiac and systemic dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388402" }, { "confidence": "medium", "disease": "Renal Failure", "glycan_involvement": "Glycosylation affects renal epithelial localization.", "mechanism": "Reduced renal clearance and altered P-gp function increase digoxin retention.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12388402" }, { "confidence": "high", "disease": "Channel catfish virus disease (CCVD)", "glycan_involvement": "No direct glycosylation involvement for IpSTING reported.", "mechanism": "IpSTING mediates type I IFN response to inhibit CCV replication and promote antiviral immunity.", "protein": "IpSTING", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12388441" }, { "confidence": "medium", "disease": "Channel catfish virus disease (CCVD)", "glycan_involvement": "Not specified.", "mechanism": "ORF41 interacts with IpSTING, potentially modulating or inhibiting host cGAS-STING pathway to evade immune response.", "protein": "ORF41", "relationship_type": "causal/immune evasion", "source_pmcid": "PMC12388441" }, { "confidence": "medium", "disease": "Channel catfish virus disease (CCVD)", "glycan_involvement": "Not specified.", "mechanism": "ORF65 interacts with IpSTING, possibly interfering with STING-mediated antiviral signaling.", "protein": "ORF65", "relationship_type": "causal/immune evasion", "source_pmcid": "PMC12388441" }, { "confidence": "medium", "disease": "Channel catfish virus disease (CCVD)", "glycan_involvement": "ORF59 is a glycoprotein; glycosylation likely mediates membrane localization and host interaction.", "mechanism": "ORF59 is a glycoprotein involved in CCV virion assembly, membrane localization, and inhibition of viral adsorption; recombinant ORF59 blocks viral entry and reduces infectious particle production.", "protein": "ORF59", "relationship_type": "causal/structural/entry", "source_pmcid": "PMC12388441" }, { "confidence": "low", "disease": "Channel catfish virus disease (CCVD)", "glycan_involvement": "Glycosylation may facilitate interaction with host immune proteins.", "mechanism": "ORF59 may interface with host pattern recognition receptors such as IpSTING, possibly influencing STING-mediated signaling and cellular stress responses.", "protein": "ORF59", "relationship_type": "potential immune modulator", "source_pmcid": "PMC12388441" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation of hemagglutinin is essential for antigenicity and immune recognition", "mechanism": "Induction of strong humoral and virus-neutralizing antibody response via nanoparticulate saponin adjuvant", "protein": "Influenza virus hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates immunogenicity and antibody accessibility", "mechanism": "Enhanced antibody response with saponin-based adjuvant, contributing to viral neutralization", "protein": "Influenza virus neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Herpes simplex virus-1 infection", "glycan_involvement": "Glycosylation of gD is critical for immune recognition and vaccine design", "mechanism": "Saponin nanocomplexes increase IgG response to recombinant gD, enhancing vaccine efficacy", "protein": "Herpes simplex virus-1 glycoprotein D (gD)", "protein_enriched": { "function": "The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane f", "gene_name": "gH", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "P06477" }, "relationship_type": "protective", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "West Nile fever", "glycan_involvement": "Envelope glycosylation affects antigenicity and immune response", "mechanism": "Saponin adjuvant boosts IgG response to recombinant envelope protein", "protein": "West Nile virus envelope protein", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Q6P6" }, "relationship_type": "protective", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Envelope glycosylation influences immunogenicity and antibody binding", "mechanism": "Nanoparticulate saponin adjuvant increases IgG response to engineered envelope proteins", "protein": "Dengue virus envelope protein (types 1 and 4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation sites modulate antigenicity and immune evasion", "mechanism": "Target for vaccine-induced neutralizing antibodies", "protein": "Influenza virus hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Herpes simplex virus-1 infection", "glycan_involvement": "N- and O-glycosylation sites affect immune recognition", "mechanism": "Target for vaccine and antibody therapies", "protein": "Herpes simplex virus-1 glycoprotein D (gD)", "protein_enriched": { "function": "The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane f", "gene_name": "gH", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "P06477" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "West Nile fever", "glycan_involvement": "N-glycosylation modulates immunogenicity", "mechanism": "Target for neutralizing antibodies in vaccine formulations", "protein": "West Nile virus envelope protein", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Q6P6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "N-glycosylation impacts antigenicity and immune response", "mechanism": "Target for vaccine-induced neutralizing antibodies", "protein": "Dengue virus envelope protein (types 1 and 4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388446" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation patterns affect diagnostic assay sensitivity", "mechanism": "Serological detection of antibodies against glycoproteins indicates immune status", "protein": "Influenza virus glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388446" }, { "confidence": "high", "disease": "Diabetic neuropathy", "glycan_involvement": "ALR2 is a glycoprotein; glycosylation may affect enzyme stability and activity.", "mechanism": "ALR2 regulates the polyol pathway; its activation leads to sorbitol accumulation, oxidative stress, and inflammation, driving neuropathy.", "protein": "Aldose reductase (ALR2)", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic ", "gene_name": "AKR1B1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15121" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Diabetic retinopathy", "glycan_involvement": "Glycosylation may modulate ALR2 localization and function.", "mechanism": "ALR2 activation increases oxidative stress and inflammation in retinal cells, contributing to retinopathy.", "protein": "Aldose reductase (ALR2)", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic ", "gene_name": "AKR1B1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15121" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation status may influence ALR2 activity in kidney cells.", "mechanism": "ALR2-driven polyol pathway activation promotes renal oxidative stress and inflammation.", "protein": "Aldose reductase (ALR2)", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic ", "gene_name": "AKR1B1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15121" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "PPAR-\u03b3 is glycosylated; glycosylation may affect receptor activation and ligand binding.", "mechanism": "PPAR-\u03b3 agonism improves insulin sensitivity, glucose uptake, and adipocyte remodeling.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin (not classical glycosylation).", "mechanism": "HbA1c reflects long-term glycemic control; increased levels indicate poor diabetes management.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12388506" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Elevated GGT indicates increased oxidative stress and is linked to insulin resistance and cardiovascular risk.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12388506" }, { "confidence": "medium", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "ALP glycosylation influences enzyme secretion and activity.", "mechanism": "ALP elevation signals hepatic inflammation or biliary dysfunction, common in diabetes complications.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may modulate receptor function.", "mechanism": "PPAR-\u03b3 activation enhances insulin sensitivity and reduces resistance.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 is a pro-inflammatory cytokine elevated in diabetes and obesity, contributing to insulin resistance.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-6 glycosylation regulates stability and bioactivity.", "mechanism": "IL-6 is elevated in diabetes and obesity, mediating inflammation and endothelial dysfunction.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388506" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation modulates immune recognition and receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding; mutations (e.g., S_69-70del, S_144del, S_501Y) increase transmissibility and immune escape.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12388554" }, { "confidence": "medium", "disease": "Severe COVID-19 pneumonia", "glycan_involvement": "Potential O-glycosylation affects RNA binding and immune modulation.", "mechanism": "Rare N_323K mutation associated with fatal outcome; N protein enhances viral replication and interferes with host antiviral responses.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388554" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation may influence virion assembly and immune evasion.", "mechanism": "M protein (M_168V mutation) acts as a scaffold for virion assembly; rare mutations may affect viral fitness.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC12388554" }, { "confidence": "medium", "disease": "Severe COVID-19 pneumonia", "glycan_involvement": "Altered glycosylation sites may affect antibody recognition.", "mechanism": "Rare S_155R, S_1111K, and other S mutations linked to increased pathogenicity and immune escape.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12388554" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Predicted glycosylation may affect protein stability and immune modulation.", "mechanism": "ORF8_10-21del mutation may modulate immune evasion; ORF8 antagonizes host immunity.", "protein": "ORF8 protein", "protein_enriched": { "function": "Plays a role in modulating the host immune response (PubMed:31986261, PubMed:35343786, PubMed:36689483). May act as a secreted virokine by mimicking interleukin-17A (IL17A), and thereby binding to the", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC8" }, "relationship_type": "causal", "source_pmcid": "PMC12388554" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may impact protein trafficking and immune evasion.", "mechanism": "ORF7a_93I mutation antagonizes host antiviral proteins and reduces MHC-I antigen presentation.", "protein": "ORF7a protein", "protein_enriched": { "function": "Plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect (PubMed:33930332). Acts by binding to BST2 and sequestering it to perinuclear region, thereby preventing its antivir", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC7" }, "relationship_type": "causal", "source_pmcid": "PMC12388554" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield modulates antibody accessibility.", "mechanism": "Target of neutralizing antibodies and vaccines; mutations may reduce vaccine efficacy.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388554" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "N protein is a diagnostic target in PCR assays; mutations may affect assay sensitivity.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388554" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns help distinguish variants.", "mechanism": "S gene mutations (e.g., S_614G) define viral lineages and transmission chains.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12388554" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Rare M_168V mutation used for lineage tracking and transmission mapping.", "protein": "Membrane glycoprotein (M)", "relationship_type": "biomarker", "source_pmcid": "PMC12388554" }, { "confidence": "high", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "FPN is a glycoprotein; glycosylation may affect stability and trafficking, but not directly discussed.", "mechanism": "RBC-FPN regulates iron export; its suppression increases intracellular iron, favoring Plasmodium growth and severity.", "protein": "Ferroportin (FPN)", "protein_enriched": { "function": "Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal ", "gene_name": "FBXO6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRD1" }, "relationship_type": "causal", "source_pmcid": "PMC12388592" }, { "confidence": "high", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "Hepcidin is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Hepcidin induces FPN degradation, restricting iron; dysregulation impacts parasite survival and anemia.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "Transferrin N-glycosylation affects iron binding and receptor interaction.", "mechanism": "Upregulated transferrin increases iron delivery, potentially enhancing parasite proliferation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388592" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "EPO glycosylation is essential for stability and bioactivity.", "mechanism": "Elevated EPO reflects compensatory erythropoiesis in response to malaria-induced anemia.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12388592" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Glycosylation may affect FPN membrane localization.", "mechanism": "Suppressed RBC-FPN leads to iron retention, oxidative stress, and hemolytic anemia.", "protein": "Ferroportin (FPN)", "protein_enriched": { "function": "Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal ", "gene_name": "FBXO6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRD1" }, "relationship_type": "causal", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "Not directly discussed.", "mechanism": "Pharmacologic inhibition (VIT-2763) improves hematologic parameters by restricting iron release.", "protein": "Ferroportin (FPN)", "protein_enriched": { "function": "Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal ", "gene_name": "FBXO6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRD1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "Sickle cell anemia", "glycan_involvement": "Not directly discussed.", "mechanism": "VIT-2763 reduces hemolysis and corrects anemia by modulating iron export.", "protein": "Ferroportin (FPN)", "protein_enriched": { "function": "Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal ", "gene_name": "FBXO6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRD1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "LCN2 glycosylation affects secretion and immune function.", "mechanism": "Elevated LCN2 indicates heightened inflammation in severe malaria.", "protein": "Lipocalin-2 (LCN2)", "relationship_type": "biomarker", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "SAA glycosylation modulates its solubility and immune interactions.", "mechanism": "Increased SAA reflects acute phase response and inflammation in malaria.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388592" }, { "confidence": "medium", "disease": "Malaria (Plasmodium infection)", "glycan_involvement": "Mutation may affect glycosylation and hepcidin binding.", "mechanism": "Q248H mutation confers resistance to hepcidin, potentially reducing parasite burden and anemia.", "protein": "Ferroportin (FPN) Q248H variant", "relationship_type": "protective", "source_pmcid": "PMC12388592" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike protein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC12388748" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation affects antibody binding and neutralization efficacy.", "mechanism": "Targeted by monoclonal antibodies and vaccine-induced antibodies to neutralize virus.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388748" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation modulates effector functions and immune response.", "mechanism": "Presence of anti-S IgG correlates with enhanced viral clearance and reduced severity.", "protein": "Anti-Spike (S) IgG", "relationship_type": "protective", "source_pmcid": "PMC12388748" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation may enhance immune effector functions.", "mechanism": "Monoclonal antibodies neutralize SARS-CoV-2 by binding Spike protein.", "protein": "Anti-Spike (S) monoclonal antibodies", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388748" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N protein is glycosylated, affecting antigenicity.", "mechanism": "Anti-N IgG indicates prior infection; used for serological diagnosis.", "protein": "SARS-CoV-2 Nucleoprotein (N)", "relationship_type": "biomarker", "source_pmcid": "PMC12388748" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation influences immune response.", "mechanism": "Detection of anti-N IgG used to distinguish infection from vaccination.", "protein": "Anti-Nucleoprotein (N) IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12388748" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation of IgG affects neutralization and Fc-mediated functions.", "mechanism": "Baseline anti-S IgG positivity is associated with greater viral load decay after treatment.", "protein": "Anti-Spike (S) IgG", "relationship_type": "protective", "source_pmcid": "PMC12388748" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Fc glycosylation may modulate immune stimulation.", "mechanism": "Early administration reduces hospitalization and mortality in SOTRs.", "protein": "Anti-Spike (S) monoclonal antibodies", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388748" }, { "confidence": "medium", "disease": "Interstitial pneumonia", "glycan_involvement": "Glycans shield Spike from immune detection, facilitating infection.", "mechanism": "Spike-mediated viral entry leads to lung infection and pneumonia.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC12388748" }, { "confidence": "medium", "disease": "Interstitial pneumonia", "glycan_involvement": "Fc glycosylation may enhance clearance of infected cells.", "mechanism": "Monoclonal antibody treatment in SOTRs with pneumonia led to recovery without sequelae.", "protein": "Anti-Spike (S) monoclonal antibodies", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388748" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "O-glycosylation affects ApoC-III stability and plasma levels.", "mechanism": "Elevated ApoC-III levels promote hypertriglyceridemia and insulin resistance, contributing to hepatic steatosis.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "causal", "source_pmcid": "PMC12388749" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "O-glycosylation modulates ApoC-III function in lipid metabolism.", "mechanism": "Increased ApoC-III impairs triglyceride clearance, exacerbating liver fat accumulation.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "causal", "source_pmcid": "PMC12388749" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may influence ApoC-III's interaction with lipoprotein receptors.", "mechanism": "Elevated plasma ApoC-III is associated with insulin resistance and diabetes risk.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388749" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "Glycosylation affects ApoC-III secretion and plasma half-life.", "mechanism": "ApoC-III gene variants increase ApoC-III expression, leading to higher triglyceride levels.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "causal", "source_pmcid": "PMC12388749" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease", "glycan_involvement": "Glycosylation may modulate ApoC-III's pro-inflammatory properties.", "mechanism": "Elevated ApoC-III promotes atherogenic dyslipidemia.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "risk factor", "source_pmcid": "PMC12388749" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation status may affect ApoC-III detection and quantification.", "mechanism": "Plasma ApoC-III levels are elevated in MASLD patients.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388749" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "No direct glycan involvement from SNPs; effect is transcriptional.", "mechanism": "ApoC-III promoter SNPs (rs2854116, rs2854117) increase ApoC-III expression, but not associated with MASLD in Turkish population.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "genetic risk (population-dependent)", "source_pmcid": "PMC12388749" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "No direct glycan involvement from SNPs; effect is transcriptional.", "mechanism": "ApoC-III SNPs (rs2854116, rs2854117) linked to increased triglyceride levels.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "genetic risk", "source_pmcid": "PMC12388749" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycan involvement.", "mechanism": "No significant association between ApoC-III SNPs and MASLD in Turkish cohort.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "non-association (Turkish population)", "source_pmcid": "PMC12388749" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "No direct glycan involvement.", "mechanism": "LDH levels higher in rs2854116 CT/CC genotype carriers, possibly reflecting increased cellular stress.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "biomarker (LDH elevation in genotype carriers)", "source_pmcid": "PMC12388749" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "p53 glycosylation may affect stability and cellular localization, influencing drug interaction.", "mechanism": "Lamellarin D and T bind p53, potentially restoring apoptosis and cell cycle arrest in prostate cancer cells.", "protein": "p53 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may modulate p53 function and drug accessibility.", "mechanism": "Lamellarin D shows strong binding to p53, leading to apoptosis induction in lung cancer cells.", "protein": "p53 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation status may influence p53's tumor suppressor activity.", "mechanism": "Lamellarin D and T interact with p53, promoting cell death in breast cancer cells.", "protein": "p53 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "high", "disease": "Multidrug-resistant cancer", "glycan_involvement": "Not directly glycosylated; no glycan involvement.", "mechanism": "Lamellarin D inhibits topoisomerase I, overcoming resistance in cancer cell lines.", "protein": "Topoisomerase I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "high", "disease": "Multidrug-resistant cancer", "glycan_involvement": "N-glycosylation of P-gp is critical for its membrane localization and drug transport function.", "mechanism": "Lamellarin T is a substrate for P-glycoprotein, potentially leading to drug efflux and reduced efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Multidrug-resistant cancer", "glycan_involvement": "Glycosylation may affect p53's ability to trigger apoptosis.", "mechanism": "Lamellarin D reverses multidrug resistance by activating p53-mediated apoptosis.", "protein": "p53 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation may correlate with mutant p53 forms.", "mechanism": "p53 mutation status is a biomarker for therapeutic response to lamellarin derivatives.", "protein": "p53 protein", "relationship_type": "biomarker", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation required for P-gp function.", "mechanism": "P-gp-mediated efflux may limit lamellarin T efficacy in breast cancer cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may modulate p53's biomarker utility.", "mechanism": "p53 status predicts response to lamellarin D treatment.", "protein": "p53 protein", "relationship_type": "biomarker", "source_pmcid": "PMC12388770" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "No glycan involvement.", "mechanism": "Lamellarin D inhibits topoisomerase I, reducing proliferation in breast cancer cells.", "protein": "Topoisomerase I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388770" }, { "confidence": "high", "disease": "Acute pharyngitis", "glycan_involvement": "Surface glycosylation aids immune evasion and tissue adherence.", "mechanism": "M protein mediates adhesion and immune evasion, enabling colonization and infection.", "protein": "M protein", "protein_enriched": { "function": "Modulates RecA activity", "gene_name": "recX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DD93" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "high", "disease": "Necrotizing fasciitis", "glycan_involvement": "Glycosylation modulates immune recognition and virulence.", "mechanism": "Certain emm types (e.g., emm1) with specific M protein variants are linked to invasive tissue destruction.", "protein": "M protein", "protein_enriched": { "function": "Modulates RecA activity", "gene_name": "recX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DD93" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "high", "disease": "Streptococcal toxic shock syndrome (STSS)", "glycan_involvement": "Glycosylation may affect toxin stability and immune interaction.", "mechanism": "SpeA acts as a superantigen, triggering massive cytokine release and systemic inflammation.", "protein": "Streptococcal pyrogenic exotoxin A (SpeA)", "protein_enriched": { "function": "Modulates arousal and anxiety. May play an important anorexigenic role (By similarity). Binds to its receptor NPSR1 with nanomolar affinity to increase intracellular calcium concentrations (PubMed:153", "gene_name": "NPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0P6" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Scarlet fever", "glycan_involvement": "Glycosylation may influence superantigenicity.", "mechanism": "SpeC superantigen activity drives rash and systemic symptoms.", "protein": "Streptococcal pyrogenic exotoxin C (SpeC)", "protein_enriched": { "function": "May play an important anorexigenic role. Modulates arousal and anxiety as well as increases locomotor activity. Binds to its receptor NPSR1 with nanomolar affinity to increase intracellular calcium co", "gene_name": "Nps", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0P8" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Glycosylation may affect cytolytic activity.", "mechanism": "Streptolysin O lyses host cells, facilitating bloodstream invasion.", "protein": "Streptolysin O", "protein_enriched": { "function": "Required for CpsD phosphorylation (By similarity). Involved in the regulation of capsular polysaccharide biosynthesis. May be part of a complex that directs the coordinated polymerization and export t", "gene_name": "cpsC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0T8" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "high", "disease": "Acute rheumatic fever", "glycan_involvement": "Carbohydrate (glycan) structure is central to immune cross-reactivity.", "mechanism": "GAC is immunogenic and implicated in molecular mimicry leading to autoimmunity.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Necrotizing fasciitis", "glycan_involvement": "Glycosylation may modulate enzymatic activity.", "mechanism": "C5a peptidase degrades complement C5a, impairing neutrophil recruitment and promoting tissue invasion.", "protein": "C5a peptidase", "protein_enriched": { "function": "Collagen-binding adhesin that mediates bacterial adherence to collagenous tissues such as cartilage (PubMed:8218209). Participates in the infectious process by acting as a virulence factor in many dif", "gene_name": "cna", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q53654" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Impetigo", "glycan_involvement": "Enzyme acts on host glycans; glycosylation may affect substrate specificity.", "mechanism": "Hyaluronidase degrades connective tissue, facilitating skin infection.", "protein": "Hyaluronidase", "protein_enriched": { "function": "Together with its co-chaperonin GroES, plays an essential role in assisting protein folding. The GroEL-GroES system forms a nano-cage that allows encapsulation of the non-native substrate proteins and", "gene_name": "groEL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0N7" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation may influence protein stability and host interaction.", "mechanism": "Streptokinase promotes fibrinolysis, aiding bacterial spread in lung tissue.", "protein": "Streptokinase", "protein_enriched": { "function": "", "gene_name": "Amy2a5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00688" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "medium", "disease": "Acute post-streptococcal glomerulonephritis", "glycan_involvement": "Glycosylation may affect substrate binding and immune modulation.", "mechanism": "SpeB degrades host proteins, contributing to immune complex formation and renal injury.", "protein": "Cysteine proteinase SpeB", "protein_enriched": { "function": "This toxin kills sensitive strains of yeast", "gene_name": "SMK1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P19972" }, "relationship_type": "causal", "source_pmcid": "PMC12388776" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily N-glycosylated; glycan shield modulates immune evasion and antibody accessibility.", "mechanism": "Mediates viral entry via CD4 and coreceptors; target of neutralizing antibodies and entry inhibitors.", "protein": "HIV-1 gp120/gp41 (Env)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12388780" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation affects antigenicity, immune evasion, and vaccine efficacy.", "mechanism": "Mediates ACE2 binding and entry; main target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike (S)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "N- and O-glycosylation modulates immune evasion and cell tropism.", "mechanism": "Mediates host cell entry; target for neutralizing antibodies and vaccines.", "protein": "Ebolavirus Glycoprotein (GP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation impacts antigenic drift, immune escape, and vaccine design.", "mechanism": "Mediates viral attachment and fusion; main target for neutralizing antibodies and vaccines.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Chikungunya", "glycan_involvement": "Glycosylation influences infectivity and immune recognition.", "mechanism": "Mediates broad cell tropism and entry; target for neutralizing antibodies.", "protein": "Chikungunya Virus Envelope", "relationship_type": "causal", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Glycosylation affects viral maturation, infectivity, and antibody binding.", "mechanism": "Envelope proteins mediate entry and are targets for neutralizing antibodies.", "protein": "Dengue Virus PrM/E", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Lassa Fever", "glycan_involvement": "Glycosylation modulates immune evasion.", "mechanism": "Mediates cell entry; target for neutralizing antibodies and drug screening.", "protein": "Lassa Virus Glycoprotein", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Nipah Virus Infection", "glycan_involvement": "Glycosylation affects infectivity and immunogenicity.", "mechanism": "Envelope glycoproteins mediate host cell entry; targets for neutralizing antibodies.", "protein": "Nipah Virus G/F", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Yellow Fever", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Envelope protein mediates entry; target for neutralizing antibodies.", "protein": "Yellow Fever Virus Envelope", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "medium", "disease": "Japanese Encephalitis", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Envelope protein mediates entry; target for neutralizing antibodies.", "protein": "Japanese Encephalitis Virus Envelope", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12388780" }, { "confidence": "high", "disease": "Acute viral pneumonia", "glycan_involvement": "N-glycosylation of F protein modulates infectivity and immune evasion.", "mechanism": "F glycoprotein mediates viral entry and cell-cell fusion, leading to infection and lung pathology.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "causal", "source_pmcid": "PMC12388842" }, { "confidence": "high", "disease": "Acute viral pneumonia", "glycan_involvement": "O-glycosylation of G protein affects host cell binding and immune recognition.", "mechanism": "G glycoprotein facilitates viral attachment to host cells, initiating infection.", "protein": "Human metapneumovirus Attachment (G) glycoprotein", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is", "gene_name": "WNT11", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "O96014" }, "relationship_type": "causal", "source_pmcid": "PMC12388842" }, { "confidence": "medium", "disease": "Hemorrhagic pneumonia", "glycan_involvement": "Glycosylation may enhance pathogenicity and tissue tropism.", "mechanism": "High viral load and F protein-mediated fusion cause severe lung damage and hemorrhage.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "causal", "source_pmcid": "PMC12388842" }, { "confidence": "medium", "disease": "Diffuse alveolar hemorrhage", "glycan_involvement": "Glycosylation status may influence severity of alveolar injury.", "mechanism": "F protein-driven infection leads to alveolar damage and hemorrhage.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "causal", "source_pmcid": "PMC12388842" }, { "confidence": "low", "disease": "Acute viral pneumonia", "glycan_involvement": "Glycosylation affects antigenicity and diagnostic utility.", "mechanism": "Autoimmune panel includes Beta-2-Glycoprotein to exclude autoimmune causes of pneumonia.", "protein": "Beta-2-Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12388842" }, { "confidence": "low", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation status may affect stability and function.", "mechanism": "Low serum albumin is indicative of liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388842" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Altered host glycosylation may affect viral entry and immune response.", "mechanism": "Diabetes increases susceptibility to severe hMPV infection due to impaired immunity.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "causal (risk factor)", "source_pmcid": "PMC12388842" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Host glycoprotein changes may influence viral pathogenesis.", "mechanism": "Liver cirrhosis predisposes to severe hMPV pneumonia due to coagulopathy and immune dysfunction.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "causal (risk factor)", "source_pmcid": "PMC12388842" }, { "confidence": "high", "disease": "Acute viral pneumonia", "glycan_involvement": "Glycosylation may affect inclusion formation and visibility.", "mechanism": "Detection of cytoplasmic eosinophilic inclusions (F protein aggregates) in lung tissue serves as a histopathological marker of hMPV infection.", "protein": "Human metapneumovirus Fusion (F) glycoprotein", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "APP", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "P05067" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388842" }, { "confidence": "medium", "disease": "Acute viral pneumonia", "glycan_involvement": "O-glycosylation influences inclusion morphology.", "mechanism": "Presence of G protein in viral inclusions may aid histopathological diagnosis.", "protein": "Human metapneumovirus Attachment (G) glycoprotein", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is", "gene_name": "WNT11", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "O96014" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388842" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "PSMA is a glycoprotein; glycosylation is essential for its membrane localization and ligand binding.", "mechanism": "PSMA is highly upregulated in mCRPC cells and targeted by radioligand therapies ([225Ac]Ac-PSMA, [177Lu]Lu-PSMA) for selective cytotoxicity.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Hormone-Sensitive Prostate Cancer (mHSPC)", "glycan_involvement": "Glycosylation maintains PSMA structure and function, enabling effective targeting.", "mechanism": "PSMA-targeted alpha therapy ([225Ac]Ac-PSMA) shows efficacy in mHSPC, with significant PSA declines.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388893" }, { "confidence": "medium", "disease": "Renal toxicity", "glycan_involvement": "Glycosylation affects PSMA expression in renal tissue.", "mechanism": "PSMA is expressed in renal proximal tubules; off-target radioligand uptake can cause nephrotoxicity.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Xerostomia", "glycan_involvement": "Glycosylation supports PSMA localization in salivary glands.", "mechanism": "PSMA is physiologically expressed in salivary glands; targeted alpha therapy leads to glandular damage and dry mouth.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC12388893" }, { "confidence": "medium", "disease": "Haematologic toxicity", "glycan_involvement": "Indirect; glycosylation not directly implicated in toxicity.", "mechanism": "Off-target radiation from PSMA-targeted therapy can affect bone marrow, causing anaemia, leukopenia, and thrombocytopenia.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "Glycosylation influences PSMA PET ligand binding and imaging sensitivity.", "mechanism": "PSMA expression assessed by PET/CT is used to select patients for targeted therapy and predict response.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "Glycosylation modulates PSMA endocytosis efficiency.", "mechanism": "PSMA internalisation via clathrin-mediated endocytosis enhances intracellular retention of radioligands, increasing cytotoxicity.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "Glycosylation affects PSMA surface density and ligand accessibility.", "mechanism": "High PSMA expression correlates with better survival and response to therapy.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "Glycosylation maintains PSMA conformation for ligand binding.", "mechanism": "PSMA-targeted radioligand therapy is effective even in beta-refractory disease, indicating a unique therapeutic mechanism.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388893" }, { "confidence": "medium", "disease": "Metastatic Castration-Resistant Prostate Cancer (mCRPC)", "glycan_involvement": "Glycosylation ensures proper PSMA targeting by both radioligands.", "mechanism": "PSMA-targeted tandem therapy ([225Ac]Ac-PSMA + [177Lu]Lu-PSMA) improves tumour control and may reduce toxicity.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388893" }, { "confidence": "high", "disease": "Persistent Parainfluenza Virus Infection", "glycan_involvement": "Glycoprotein density and glycosylation state modulate complement activation.", "mechanism": "F glycoprotein expression on cell surface triggers complement activation and lysis in acute infection; downregulation in persistent infection confers resistance.", "protein": "PIV5 Fusion (F) Glycoprotein", "protein_enriched": { "function": "Encapsidates the genome protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication. The NC have a helical organ", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04873" }, "relationship_type": "causal", "source_pmcid": "PMC12388906" }, { "confidence": "high", "disease": "Persistent Parainfluenza Virus Infection", "glycan_involvement": "Sialic acid cleavage by HN alters glycan landscape and complement factor binding.", "mechanism": "HN expression reduces cell surface sialic acid, affecting complement regulation; reduced HN in PI restores sialic acid but does not restore complement sensitivity.", "protein": "PIV5 Hemagglutinin-Neuraminidase (HN) Glycoprotein", "protein_enriched": { "function": "Inhibits host transcriptional machinery, by producing modifications to the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II. Inhibits phosphorylation at serine 2 in the heptap", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04874" }, "relationship_type": "causal", "source_pmcid": "PMC12388906" }, { "confidence": "medium", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation of H protein affects receptor binding and immune evasion.", "mechanism": "MeV H glycoprotein binds and downregulates CD46, increasing complement sensitivity and contributing to neuropathology.", "protein": "Measles Virus Hemagglutinin (H) Glycoprotein", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P69353" }, "relationship_type": "causal", "source_pmcid": "PMC12388906" }, { "confidence": "medium", "disease": "Chronic HIV Infection", "glycan_involvement": "Extensive glycosylation shields epitopes and modulates complement activation.", "mechanism": "gp160 directly activates classical complement pathway, contributing to immune activation.", "protein": "HIV gp160", "relationship_type": "causal", "source_pmcid": "PMC12388906" }, { "confidence": "medium", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation required for CD46 function and surface expression.", "mechanism": "CD46 acts as a complement regulator; its downregulation by MeV H increases complement-mediated cell lysis.", "protein": "CD46", "protein_enriched": { "function": "Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in th", "gene_name": "CD46", "glycan_count": 60, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G61846BY", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G34989PA", "G40834TG", "G41071NU", "G43223CG", "G45395BF", "G48414YA", "G59324HL", "G60033FS", "G60177UT", "G62765YT", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G94470IW", "G98611JV", "G57321FI", "G03644CB", "G04854VP", "G07810QS", "G08290VR", "G12341GU", "G13131HA", "G15169WU", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G41247ZX", "G43669FQ", "G50856PC", "G57776ZS", "G61256FT", "G69521XL", "G76417NN", "G78649WQ", "G82443XX", "G89827JR", "G90382BL", "G92275SC", "G92551JA", "G94106MV", "G49108TO" ], "uniprot_id": "P15529" }, "relationship_type": "protective", "source_pmcid": "PMC12388906" }, { "confidence": "low", "disease": "Persistent Parainfluenza Virus Infection", "glycan_involvement": "Glycosylation required for CD55 function.", "mechanism": "CD55 upregulation (mRNA) in PI HEp2 cells, but not at protein level; not correlated with resistance to complement lysis.", "protein": "CD55", "protein_enriched": { "function": "Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI)", "gene_name": "DDT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30046" }, "relationship_type": "protective", "source_pmcid": "PMC12388906" }, { "confidence": "medium", "disease": "Persistent Parainfluenza Virus Infection", "glycan_involvement": "CFH binding depends on sialylated glycans.", "mechanism": "CFH binds sialic acid to inhibit complement activation; restoration of sialic acid in PI cells does not restore complement sensitivity.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "protective", "source_pmcid": "PMC12388906" }, { "confidence": "low", "disease": "Long COVID", "glycan_involvement": "Glycoprotein expression modulates complement activation.", "mechanism": "Analogy: Reduced viral glycoprotein expression in persistent infection may underlie complement evasion and chronic inflammation in long COVID.", "protein": "PIV5 Fusion (F) Glycoprotein", "protein_enriched": { "function": "Encapsidates the genome protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication. The NC have a helical organ", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04873" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388906" }, { "confidence": "low", "disease": "Chronic Chikungunya", "glycan_involvement": "Glycoprotein glycosylation modulates immune recognition.", "mechanism": "Analogy: Persistent viral glycoprotein expression correlates with complement activation and chronic disease.", "protein": "PIV5 Hemagglutinin-Neuraminidase (HN) Glycoprotein", "protein_enriched": { "function": "Inhibits host transcriptional machinery, by producing modifications to the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II. Inhibits phosphorylation at serine 2 in the heptap", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04874" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388906" }, { "confidence": "low", "disease": "Chronic Hepatitis C", "glycan_involvement": "Glycosylation modulates complement activation and immune evasion.", "mechanism": "Analogy: Persistent viral glycoprotein expression and complement evasion mechanisms are shared with HCV.", "protein": "PIV5 Fusion (F) Glycoprotein", "protein_enriched": { "function": "Encapsidates the genome protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication. The NC have a helical organ", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04873" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388906" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects TfR trafficking and ligand binding, influencing delivery efficiency.", "mechanism": "TfR-mediated transcytosis is exploited for targeted delivery of anti-A\u03b2 antibodies and nanoparticles across the BBB.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates IR function and BBB transport.", "mechanism": "IR-mediated transcytosis is used for brain delivery of therapeutics; IR density is altered in AD.", "protein": "Insulin receptor (IR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation regulates LRP1 ligand binding and endocytosis.", "mechanism": "LRP1 facilitates A\u03b2 clearance and is targeted for drug delivery across the BBB.", "protein": "Low-density lipoprotein receptor-related protein 1 (LRP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation is essential for GBA1 folding, stability, and lysosomal targeting.", "mechanism": "GBA1 mutations cause lysosomal dysfunction, promoting \u03b1-synuclein aggregation.", "protein": "Glucocerebrosidase 1 (GBA1)", "relationship_type": "causal", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation modulate APP processing and A\u03b2 production.", "mechanism": "APP processing generates A\u03b2 peptides that aggregate into plaques.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Prion diseases", "glycan_involvement": "N-glycosylation affects PrP folding, aggregation, and pathogenicity.", "mechanism": "Misfolded PrP aggregates cause neurodegeneration.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC12388969" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates FcRn-IgG interactions and transcytosis.", "mechanism": "FcRn pathway is engineered to enhance antibody delivery to the brain.", "protein": "Neonatal Fc receptor (FcRn)", "protein_enriched": { "function": "Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degrad", "gene_name": "DET1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7L5Y6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation is critical for CD47 function and recognition by immune cells.", "mechanism": "CD47 on exosomes provides 'don't eat me' signals, prolonging circulation and enhancing delivery.", "protein": "Cluster of Differentiation 47 (CD47)", "relationship_type": "protective", "source_pmcid": "PMC12388969" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects TREM2 stability and cell surface expression.", "mechanism": "TREM2 modulates microglial activation and neuroinflammation in AD.", "protein": "Triggering Receptor Expressed on Myeloid cells 2 (TREM2)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation is required for GDNF secretion and activity.", "mechanism": "GDNF delivered via AAV vectors promotes dopaminergic neuron survival.", "protein": "Glial cell line-derived neurotrophic factor (GDNF)", "protein_enriched": { "function": "Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake (PubMed:8493557). Acts by binding to its corecept", "gene_name": "GDNF", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P39905" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388969" }, { "confidence": "high", "disease": "Acute graft-versus-host disease (aGVHD)", "glycan_involvement": "Glycosylation affects ATG's immunogenicity and clearance.", "mechanism": "ATG depletes T cells to prevent aGVHD after HSCT.", "protein": "Antithymocyte globulin (ATG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Acute graft-versus-host disease (aGVHD)", "glycan_involvement": "Glycosylation modulates antibody-dependent cytotoxicity.", "mechanism": "Alemtuzumab targets CD52 on lymphocytes to reduce aGVHD risk.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Acute graft-versus-host disease (aGVHD)", "glycan_involvement": "Glycosylation influences drug metabolism and immune interactions.", "mechanism": "Cyclosporine inhibits T-cell activation to prevent aGVHD.", "protein": "Cyclosporine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Acute graft-versus-host disease (aGVHD)", "glycan_involvement": "Prodrug glycosylation affects bioavailability.", "mechanism": "Inhibits lymphocyte proliferation to prevent aGVHD.", "protein": "Mycophenolate mofetil", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation affects ALK stability and serum levels.", "mechanism": "Elevated ALK indicates hepatic toxicity post-busulfan.", "protein": "Alkaline phosphatase (ALK)", "relationship_type": "biomarker", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation modulates enzyme activity and clearance.", "mechanism": "ALT elevation signals hepatocellular injury after conditioning.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation influences enzyme half-life.", "mechanism": "AST elevation reflects hepatic or muscle toxicity.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Graft failure", "glycan_involvement": "HLA glycosylation affects immune recognition and compatibility.", "mechanism": "HLA mismatch increases risk of graft failure post-HSCT.", "protein": "Human leukocyte antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC12389012" }, { "confidence": "medium", "disease": "Primary immunodeficiency", "glycan_involvement": "Glycosylation impacts ATG's efficacy and immunogenicity.", "mechanism": "ATG used for immunosuppression in HSCT for immunodeficiencies.", "protein": "Antithymocyte globulin (ATG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "medium", "disease": "Metabolic disorder", "glycan_involvement": "Glycosylation modulates antibody function.", "mechanism": "Alemtuzumab used for immunosuppression in HSCT for metabolic disorders.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389012" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycosylation of GP5 modulates immune recognition and may shield epitopes from neutralizing antibodies.", "mechanism": "GP5 mediates viral entry into host cells and is critical for immune recognition; genetic variation in GP5 (including via recombination) contributes to viral pathogenicity and immune evasion.", "protein": "Glycoprotein 5 (GP5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389020" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycosylation sites on GP5 influence antigenicity and are used to distinguish lineages.", "mechanism": "ORF5 (encoding GP5) is the primary target for lineage classification and molecular epidemiology of PRRSV-2.", "protein": "Glycoprotein 5 (GP5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389020" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycosylation patterns on GP5 affect vaccine efficacy by altering epitope exposure.", "mechanism": "GP5 is a major target for vaccine development due to its role in viral entry and immune response.", "protein": "Glycoprotein 5 (GP5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389020" }, { "confidence": "high", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation required for surface expression and macrophage recognition.", "mechanism": "F4/80 marks macrophage infiltration in lung tissue, correlating with inflammation severity in H1N1 pneumonia.", "protein": "F4/80", "protein_enriched": { "function": "May have regulatory role in cell division or differentiation in response to extracellular signals", "gene_name": "Skil", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q60665" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation may affect stability and activity.", "mechanism": "GPX4 upregulation by RHDS inhibits ferroptosis, protecting lung tissue from H1N1-induced oxidative damage.", "protein": "GPX4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation influences transporter function.", "mechanism": "SLC7A11 upregulation supports glutathione synthesis, reducing ferroptosis and lung injury.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation may modulate nuclear localization and activity.", "mechanism": "Nrf2 activation by RHDS enhances antioxidant response, limiting ferroptosis and inflammation.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation affects stability and transcriptional activity.", "mechanism": "HIF-1\u03b1 upregulation promotes viral replication and inflammation; RHDS suppresses HIF-1\u03b1 to reduce injury.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12389041" }, { "confidence": "medium", "disease": "H1N1 viral pneumonia", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "COX2 upregulation drives inflammatory mediator release; RHDS inhibits COX2 to attenuate inflammation.", "protein": "COX2", "relationship_type": "causal", "source_pmcid": "PMC12389041" }, { "confidence": "medium", "disease": "Ferroptosis-induced tissue damage", "glycan_involvement": "Glycosylation may affect enzyme localization.", "mechanism": "ACSL4 promotes lipid peroxidation and ferroptosis; RHDS downregulates ACSL4 to protect tissue.", "protein": "ACSL4", "protein_enriched": { "function": "Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids ", "gene_name": "ACSL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95573" }, "relationship_type": "causal", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation required for granule targeting and activity.", "mechanism": "MPO marks neutrophil infiltration and oxidative stress in lung injury; RHDS reduces MPO levels.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "NP is glycosylated for viral assembly and immune evasion.", "mechanism": "NP mRNA levels indicate viral load; RHDS reduces NP expression, reflecting antiviral effect.", "protein": "NP (Influenza nucleoprotein)", "protein_enriched": { "function": "Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. T", "gene_name": "NP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03466" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389041" }, { "confidence": "medium", "disease": "Ferroptosis-induced tissue damage", "glycan_involvement": "N-glycosylation essential for surface expression and iron binding.", "mechanism": "CD71 mediates iron uptake, promoting ferroptosis; RHDS downregulates CD71 to limit iron accumulation.", "protein": "CD71 (Transferrin receptor)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (By similarity). Endosomal acidification leads to iron release. The ", "gene_name": "Tfrc", "glycan_count": 7, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G77547TA", "G05724UK", "G06110VR", "G72747WU", "G74724QE", "G47246VB", "G49108TO" ], "uniprot_id": "Q62351" }, "relationship_type": "causal", "source_pmcid": "PMC12389041" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "N-glycosylation of HA modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry into host cells via sialic acid binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "N-glycosylation affects NA enzymatic activity and antigenicity.", "mechanism": "NA cleaves sialic acids to facilitate viral release from host cells.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12389115" }, { "confidence": "medium", "disease": "Scrub typhus", "glycan_involvement": "Potential O-glycosylation may affect antigenicity and immune recognition.", "mechanism": "tsa56 is a major surface antigen of Orientia tsutsugamushi, used for molecular diagnosis and genotyping.", "protein": "tsa56 protein", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Scrub typhus", "glycan_involvement": "N-glycosylation critical for IgM structure and function.", "mechanism": "IgM against tsa56 indicates acute infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Scrub typhus", "glycan_involvement": "N-glycosylation modulates IgG effector functions.", "mechanism": "IgG against tsa56 indicates current or past infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Co-infection (Orientia tsutsugamushi + Influenza A)", "glycan_involvement": "N-glycosylation required for IL-6 secretion and stability.", "mechanism": "Elevated IL-6 reflects synergistic inflammation and correlates with disease severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12389115" }, { "confidence": "medium", "disease": "Scrub typhus", "glycan_involvement": "Glycosylation influences TNF-\u03b1 receptor binding.", "mechanism": "Karp genotype induces higher TNF-\u03b1, contributing to organ injury.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Co-infection (Orientia tsutsugamushi + Influenza A)", "glycan_involvement": "N-glycosylation affects PCT stability and detection.", "mechanism": "Elevated PCT indicates systemic bacterial infection and inflammation.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Co-infection (Orientia tsutsugamushi + Influenza A)", "glycan_involvement": "Glycosylation modulates CRP solubility and function.", "mechanism": "CRP elevation reflects acute phase response and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "medium", "disease": "Scrub typhus", "glycan_involvement": "Glycosylation affects albumin stability and half-life.", "mechanism": "Hypoalbuminemia indicates severe infection and systemic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389115" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "P-glycoprotein is N-glycosylated, which is essential for its stability and localization.", "mechanism": "Curcumin derivatives inhibit P-glycoprotein, potentially overcoming drug efflux-mediated resistance in glioblastoma cells.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "BCRP is N-glycosylated, affecting its trafficking and function.", "mechanism": "Curcumin derivatives inhibit BCRP, reducing multidrug resistance in glioblastoma.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "high", "disease": "Drug resistance in cancer", "glycan_involvement": "N-glycosylation is required for P-glycoprotein function in drug efflux.", "mechanism": "Overexpression of P-glycoprotein leads to efflux of chemotherapeutics, causing multidrug resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12389136" }, { "confidence": "high", "disease": "Drug resistance in cancer", "glycan_involvement": "N-glycosylation is important for BCRP stability and activity.", "mechanism": "BCRP mediates efflux of drugs, contributing to resistance in various cancers including glioblastoma.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "causal", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "OCT2 is N-glycosylated, which modulates its cell surface expression.", "mechanism": "Curcumin derivatives interact with OCT2, potentially affecting drug uptake in glioblastoma cells.", "protein": "Organic Cation Transporter 2 (OCT2/SLC22A2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation is necessary for P-glycoprotein's drug transport function.", "mechanism": "Inhibition of P-glycoprotein by curcumin derivatives may enhance efficacy of chemotherapeutics in various cancers.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation affects BCRP's localization and function.", "mechanism": "Inhibition of BCRP by curcumin derivatives may improve drug retention in cancer cells.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation modulates OCT2 function.", "mechanism": "Interaction with OCT2 may influence drug pharmacokinetics in cancer therapy.", "protein": "Organic Cation Transporter 2 (OCT2/SLC22A2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation is required for biomarker detection and function.", "mechanism": "P-glycoprotein expression is associated with poor prognosis and drug resistance in glioblastoma.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12389136" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation is important for BCRP's biomarker utility.", "mechanism": "BCRP expression correlates with multidrug resistance phenotype in glioblastoma.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "biomarker", "source_pmcid": "PMC12389136" }, { "confidence": "high", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Likely involves glycosylation for proper folding and function of resistance protein.", "mechanism": "Confers broad-spectrum resistance by activating basal defense and PTI pathways, suppressing in planta bacterial growth.", "protein": "bs5 gene product", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Bacterial spot of tomato (BST)", "glycan_involvement": "Glycosylation may be required for stability and signaling.", "mechanism": "Provides resistance against multiple Xanthomonas spp. including emerging races.", "protein": "bs5 gene product", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "high", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Glycosylation may affect protein localization and activity.", "mechanism": "Key target for breeding durable resistance in pepper cultivars.", "protein": "bs5 gene product", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Potential glycosylation for function, but less effective alone.", "mechanism": "Provides limited resistance alone; enhances resistance when stacked with bs5.", "protein": "bs6 gene product", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Glycosylation may be involved in protein stability.", "mechanism": "Confers resistance to X. hortorum pv. gardneri; additive effect with bs5.", "protein": "bs8 gene product", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "high", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "N-glycosylation required for receptor function and pathogen recognition.", "mechanism": "Upregulated in bs5-mediated resistance; recognizes bacterial flagellin and triggers PTI.", "protein": "FLS2", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "Defense marker upregulated in bs5-mediated resistance.", "protein": "PR-1", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "high", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Glycosylation status may influence biomarker reliability.", "mechanism": "Presence of bs5 allele predicts resistance phenotype.", "protein": "bs5 gene product", "relationship_type": "biomarker", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Defective glycosylation may impair resistance.", "mechanism": "Loss-of-function in bs5 leads to susceptibility.", "protein": "bs5 gene product", "relationship_type": "causal", "source_pmcid": "PMC12389147" }, { "confidence": "high", "disease": "Bacterial leaf spot of pepper (BSP)", "glycan_involvement": "Glycosylation may stabilize protein interactions in gene pyramids.", "mechanism": "Triple stacking with bs6 and bs8 provides strongest resistance, especially under heat stress.", "protein": "bs5 gene product", "relationship_type": "protective", "source_pmcid": "PMC12389147" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "gB is highly glycosylated, influencing immune recognition.", "mechanism": "Antibodies against CMV gB associated with protection against arterial stiffness in transplant recipients.", "protein": "Cytomegalovirus glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate toge", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 19, "glytoucan_ids": [], "uniprot_id": "P06473" }, "relationship_type": "protective", "source_pmcid": "PMC12389153" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "IE-1 is glycosylated, affecting antigenicity.", "mechanism": "Elevated anti-IE-1 antibody responses indicate frequent CMV reactivation and correlate with arterial stiffness.", "protein": "Cytomegalovirus Immediate-Early 1 (IE-1)", "protein_enriched": { "function": "Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity). Expression of IE1 and IE2 prote", "gene_name": "UL123", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13202" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "sCD14 is N-glycosylated, affecting stability and function.", "mechanism": "Plasma sCD14 levels correlate with CMV antibody levels in PLWH who develop CAD, indicating monocyte activation.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "LBP is N-glycosylated, modulating ligand binding.", "mechanism": "LBP levels correlate with CMV antibody levels in PLWH who develop CAD, reflecting systemic inflammation.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "CXCL10 is glycosylated, influencing chemokine activity.", "mechanism": "CXCL10 levels correlate with CMV antibody levels in PLWH who develop CAD, indicating immune activation.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "IL-6 is glycosylated, affecting receptor binding.", "mechanism": "IL-6 levels correlate with CMV antibody levels in PLWH who develop CAD, reflecting pro-inflammatory state.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "D-dimer is a glycoprotein complex, glycosylation affects clearance.", "mechanism": "D-dimer levels marginally correlate with CMV antibody levels in PLWH who develop CAD, indicating coagulation activation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "VCAM-1 is N-glycosylated, modulating cell adhesion.", "mechanism": "VCAM-1 levels correlate with CMV antibody levels near CAD diagnosis, reflecting endothelial activation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389153" }, { "confidence": "medium", "disease": "End-organ disease (CMV)", "glycan_involvement": "UL18 is glycosylated, affecting immune evasion.", "mechanism": "UL18 modulates NK cell function, influencing CMV pathogenesis and inflammation.", "protein": "CMV UL18", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QF67" }, "relationship_type": "causal", "source_pmcid": "PMC12389153" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "US28 is glycosylated, influencing receptor function.", "mechanism": "US28 modulates chemokine signaling, potentially enhancing vascular inflammation and CAD risk.", "protein": "CMV US28", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QF65" }, "relationship_type": "causal", "source_pmcid": "PMC12389153" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Folate receptor is a glycoprotein; glycosylation mediates cell surface localization and ligand binding.", "mechanism": "Folate-conjugated amphiphilic cyclodextrin nanoparticles target folate receptor-expressing breast cancer cells for enhanced drug delivery.", "protein": "Folate Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation patterns on MCF-7 cells may influence nanoparticle-cell interactions.", "mechanism": "Amphiphilic cyclodextrin nanoparticles interact with tumor cell glycoproteins to enhance uptake and cytotoxicity of encapsulated drugs.", "protein": "MCF-7 cell surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "high", "disease": "Heparin Overdose", "glycan_involvement": "Heparin is a glycosaminoglycan; its sulfation/glycosylation is essential for binding.", "mechanism": "Amphiphilic multi-charged cyclodextrins neutralize heparin via multivalent binding, serving as anti-heparin coagulants.", "protein": "Heparin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "medium", "disease": "Drug-induced Nephrotoxicity", "glycan_involvement": "Glycosylation maintains cell membrane integrity; non-disruptive interaction is beneficial.", "mechanism": "Amphiphilic cyclodextrins show low toxicity and do not disrupt immune cell glycoproteins, reducing nephrotoxicity risk.", "protein": "Polymorphonuclear cell surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12389205" }, { "confidence": "high", "disease": "Solid Tumors", "glycan_involvement": "Glycosylation of folate receptor is critical for its function and targeting.", "mechanism": "Folate-targeted amphiphilic cyclodextrin nanoparticles enable selective drug delivery to folate receptor-positive solid tumors.", "protein": "Folate Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "medium", "disease": "Solid Tumors", "glycan_involvement": "Tumor glycoprotein glycosylation may modulate nanoparticle uptake.", "mechanism": "Cyclodextrin-based nanoparticles enhance drug delivery to solid tumors via interactions with tumor glycoproteins.", "protein": "MCF-7 cell surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "low", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation status may affect biomarker detection.", "mechanism": "MCF-7 glycoprotein expression is used to assess nanoparticle targeting and cytotoxicity.", "protein": "MCF-7 cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12389205" }, { "confidence": "medium", "disease": "Coagulation Disorder", "glycan_involvement": "Heparin's glycan structure is essential for its biological activity and neutralization.", "mechanism": "Amphiphilic cyclodextrins act as heparin antagonists in coagulation disorders.", "protein": "Heparin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "low", "disease": "Drug-induced Nephrotoxicity", "glycan_involvement": "Glycosylation ensures cell viability during drug exposure.", "mechanism": "Non-toxic amphiphilic cyclodextrins preserve immune cell function, reducing nephrotoxicity.", "protein": "Polymorphonuclear cell surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12389205" }, { "confidence": "medium", "disease": "Glioblastoma (9L gliosarcoma)", "glycan_involvement": "Glycosylation of folate receptor supports targeting efficacy.", "mechanism": "Folate-targeted cyclodextrin nanoparticles improve drug delivery and survival in gliosarcoma models.", "protein": "Folate Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389205" }, { "confidence": "high", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects its stability and receptor binding.", "mechanism": "TNF-\u03b1 mediates mucosal inflammation and immune activation in IBS; inhibition reduces inflammation and symptoms.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389248" }, { "confidence": "medium", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "PIK3CD glycosylation may modulate its localization and activity in immune cells.", "mechanism": "PIK3CD regulates immune cell signaling; gain-of-function mutations linked to GI symptoms and mucosal inflammation.", "protein": "PIK3CD", "protein_enriched": { "function": "Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916). Uses AT", "gene_name": "PIK3CD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00329" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389248" }, { "confidence": "medium", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "PRKCD glycosylation can affect its cellular localization and function.", "mechanism": "PRKCD influences epithelial barrier integrity and immune tolerance; dysregulation may contribute to IBS pathogenesis.", "protein": "PRKCD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389248" }, { "confidence": "low", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "XIAP glycosylation may regulate its stability and anti-apoptotic activity.", "mechanism": "XIAP inhibits apoptosis; altered expression may affect mucosal cell survival in IBS.", "protein": "XIAP", "protein_enriched": { "function": "Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as", "gene_name": "XIAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P98170" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389248" }, { "confidence": "low", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "Glycosylation of ABCB1 affects its trafficking and drug transport activity.", "mechanism": "ABCB1 regulates drug efflux and epithelial barrier function; altered activity may influence IBS symptoms.", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12389248" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and activity.", "mechanism": "TNF-\u03b1 drives inflammation in colitis; inhibition ameliorates colon damage and symptoms.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389248" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Glycosylation may influence PIK3CD function in immune responses.", "mechanism": "PIK3CD signaling contributes to immune cell activation and mucosal inflammation in colitis.", "protein": "PIK3CD", "protein_enriched": { "function": "Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916). Uses AT", "gene_name": "PIK3CD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00329" }, "relationship_type": "causal", "source_pmcid": "PMC12389248" }, { "confidence": "low", "disease": "Type II Diabetes Mellitus", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interactions.", "mechanism": "TNF-\u03b1 is involved in inflammatory pathways linked to insulin resistance.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389248" }, { "confidence": "low", "disease": "Non-small-cell Lung Cancer", "glycan_involvement": "Glycosylation may regulate PIK3CD activity in cancer cells.", "mechanism": "PIK3CD signaling is implicated in cancer cell survival and metabolism.", "protein": "PIK3CD", "protein_enriched": { "function": "Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916). Uses AT", "gene_name": "PIK3CD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00329" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389248" }, { "confidence": "low", "disease": "Platinum Drug Resistance", "glycan_involvement": "Glycosylation modulates ABCB1 drug transport efficiency.", "mechanism": "ABCB1 mediates drug efflux, contributing to platinum drug resistance in cancer.", "protein": "ABCB1", "relationship_type": "causal", "source_pmcid": "PMC12389248" }, { "confidence": "high", "disease": "HSV-1 infection", "glycan_involvement": "gB is a major glycoprotein mediating viral entry and spread; glycosylation critical for function", "mechanism": "gB DNA levels used to quantify viral load in trigeminal ganglia and correlate with infection/latency status", "protein": "HSV-1 glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope and binds to the host cell entry receptors MYH9/NMMHC-IIA and MYH10/NMMHC-IIB, promoting the virus entry into host cells. Esse", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P10211" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 latency", "glycan_involvement": "Glycosylation of gB may affect immune evasion and latency establishment", "mechanism": "gB DNA levels reflect latent viral genome load in neurons", "protein": "HSV-1 glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope and binds to the host cell entry receptors MYH9/NMMHC-IIA and MYH10/NMMHC-IIB, promoting the virus entry into host cells. Esse", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P10211" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 reactivation", "glycan_involvement": "Glycosylation may modulate reactivation efficiency", "mechanism": "gB DNA and protein expression increase during reactivation; used to monitor reactivation events", "protein": "HSV-1 glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope and binds to the host cell entry receptors MYH9/NMMHC-IIA and MYH10/NMMHC-IIB, promoting the virus entry into host cells. Esse", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P10211" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 reactivation", "glycan_involvement": "Serpina6 is a glycoprotein; glycosylation required for stability and function", "mechanism": "KLF15 knockout reduces Serpina6, increasing free corticosterone, which may enhance HSV-1 reactivation in males", "protein": "Serpina6 (corticosteroid-binding globulin)", "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "high", "disease": "HSV-1 infection", "glycan_involvement": "Indirect; KLF15 regulates expression of viral glycoproteins via transcriptional activation", "mechanism": "KLF15 enhances HSV-1 replication during acute infection by transactivating viral immediate early promoters", "protein": "KLF15", "protein_enriched": { "function": "Transcriptional regulator that binds to the GA element of the CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart (By similarity). Is a repressor of CC", "gene_name": "KLF15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIH9" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 latency", "glycan_involvement": "Indirect; affects viral gene expression including glycoproteins", "mechanism": "KLF15 influences establishment and maintenance of latency, especially in female mice", "protein": "KLF15", "protein_enriched": { "function": "Transcriptional regulator that binds to the GA element of the CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart (By similarity). Is a repressor of CC", "gene_name": "KLF15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIH9" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 reactivation", "glycan_involvement": "Indirect; impacts viral glycoprotein expression", "mechanism": "KLF15 modulates reactivation kinetics; its absence prolongs reactivation in males", "protein": "KLF15", "protein_enriched": { "function": "Transcriptional regulator that binds to the GA element of the CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart (By similarity). Is a repressor of CC", "gene_name": "KLF15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIH9" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "high", "disease": "HSV-1 reactivation", "glycan_involvement": "Indirect; GR regulates expression of viral glycoproteins", "mechanism": "GR activation by stress/corticosteroids triggers HSV-1 reactivation via transactivation of viral promoters", "protein": "Glucocorticoid receptor (GR)", "protein_enriched": { "function": "Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mi", "gene_name": "NR3C1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P04150" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "Herpes stromal keratitis", "glycan_involvement": "Glycosylation critical for immune evasion and tissue tropism", "mechanism": "gB is essential for HSV-1 entry and spread in corneal tissue, contributing to keratitis", "protein": "HSV-1 glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope and binds to the host cell entry receptors MYH9/NMMHC-IIA and MYH10/NMMHC-IIB, promoting the virus entry into host cells. Esse", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P10211" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "medium", "disease": "HSV-1 encephalitis", "glycan_involvement": "Glycosylation may affect neurotropism and immune evasion", "mechanism": "gB mediates neuroinvasion and spread in CNS, contributing to encephalitis", "protein": "HSV-1 glycoprotein B (gB)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope and binds to the host cell entry receptors MYH9/NMMHC-IIA and MYH10/NMMHC-IIB, promoting the virus entry into host cells. Esse", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P10211" }, "relationship_type": "causal", "source_pmcid": "PMC12389256" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389261" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects S protein binding affinity.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via S protein binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation stabilizes surface expression.", "mechanism": "Elevated PD-L1 expression correlates with disease severity and immune suppression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for VEGF secretion and activity.", "mechanism": "Increased VEGF levels associated with hyperinflammation, ARDS, and vascular leakage.", "protein": "VEGF", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates S protein-host interactions.", "mechanism": "S protein-mediated endothelial infection contributes to endothelial dysfunction and thrombosis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "Glycosylation essential for VEGF function.", "mechanism": "Elevated VEGF promotes vascular permeability, contributing to pulmonary edema in ARDS.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "Cytokine Storm Syndrome (CSS)", "glycan_involvement": "Glycosylation stabilizes PD-L1 and modulates immune checkpoint function.", "mechanism": "High PD-L1 expression reflects immune dysregulation during cytokine storm.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "N-glycosylation affects ACE2 stability and localization.", "mechanism": "ACE2 downregulation after viral entry may worsen lung injury and ARDS.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/protective", "source_pmcid": "PMC12389261" }, { "confidence": "medium", "disease": "Cytokine Storm Syndrome (CSS)", "glycan_involvement": "Glycan shield modulates immune recognition.", "mechanism": "S protein triggers immune activation leading to cytokine storm.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389261" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for PD-L1 stability and function.", "mechanism": "PD-L1/PD-1 axis modulation may improve immune response to infection.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389261" }, { "confidence": "high", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "P-gp is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "ESRD leads to a 34% reduction in intestinal P-gp abundance, altering drug absorption and increasing drug exposure.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "OATP1B1/3 are glycoproteins; glycosylation affects trafficking and substrate recognition.", "mechanism": "ESRD causes a 75% reduction in hepatic OATP1B1/3 abundance, impairing hepatic drug uptake and increasing systemic drug levels.", "protein": "OATP1B1/3", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "BCRP is a glycoprotein; glycosylation is required for proper folding and function.", "mechanism": "ESRD results in a 100% increase in ileal BCRP abundance, altering drug efflux and disposition.", "protein": "BCRP", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "medium", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "AGP is highly glycosylated; glycan changes may affect drug binding.", "mechanism": "AGP levels increase by 52\u201378% in ESRD, affecting drug binding and free drug levels.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389332" }, { "confidence": "medium", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "HSA is glycosylated; glycan status may modulate binding properties.", "mechanism": "HSA levels decrease by 27\u201329% in ESRD, impacting drug binding and pharmacokinetics.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "Adverse Drug Reactions (ADR)", "glycan_involvement": "Glycosylation is critical for P-gp function; altered glycosylation may further modulate ADR risk.", "mechanism": "Reduced P-gp in ESRD increases oral drug absorption, raising ADR risk for P-gp substrates.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "Statin-Associated Muscle Symptoms (SAMS)", "glycan_involvement": "Glycosylation affects OATP1B1/3 function and statin transport.", "mechanism": "Reduced OATP1B1/3 in ESRD increases statin exposure, raising risk of muscle toxicity.", "protein": "OATP1B1/3", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "medium", "disease": "Statin-Associated Muscle Symptoms (SAMS)", "glycan_involvement": "BCRP glycosylation is required for function; changes may affect statin efflux.", "mechanism": "Increased BCRP in ESRD alters statin disposition, potentially impacting muscle toxicity risk.", "protein": "BCRP", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "Statin-Associated Muscle Symptoms (SAMS)", "glycan_involvement": "Glycosylation is essential for P-gp activity.", "mechanism": "Reduced intestinal P-gp increases statin absorption, contributing to higher muscle exposure and SAMS risk.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "Adverse Drug Reactions (ADR)", "glycan_involvement": "Glycosylation modulates OATP1B1/3 substrate specificity and function.", "mechanism": "Reduced OATP1B1/3 increases exposure to multiple drugs, raising ADR risk in ESRD.", "protein": "OATP1B1/3", "relationship_type": "causal", "source_pmcid": "PMC12389332" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum stability and detection.", "mechanism": "Elevated AFP is used as a biomarker for HCC in MASLD progression.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "high", "disease": "Advanced Liver Disease (ALD)", "glycan_involvement": "Albumin glycosylation status can affect its half-life and function.", "mechanism": "Low serum albumin indicates impaired liver synthetic function in ALD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation of clotting factors is essential for their secretion and function.", "mechanism": "Elevated INR reflects reduced synthesis of glycosylated clotting factors in cirrhosis.", "protein": "INR (prothrombin complex)", "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function; altered in liver disease.", "mechanism": "Thrombocytopenia (low platelets) is a marker for portal hypertension in liver disease.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)", "glycan_involvement": "Cytokeratin-18 is glycosylated; glycan status may affect fragment release.", "mechanism": "Serum cytokeratin-18 fragments indicate hepatocyte apoptosis in MASLD.", "protein": "Cytokeratin-18 fragments", "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "high", "disease": "MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "SGLT2 inhibitors reduce hepatic steatosis, inflammation, and fibrosis.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "LDL receptor glycosylation is critical for ligand binding and clearance.", "mechanism": "LDL receptor function affects lipid profile and cardiovascular risk in MASLD.", "protein": "LDL receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)", "glycan_involvement": "GLP-1 receptor is glycosylated; glycosylation modulates receptor signaling.", "mechanism": "GLP-1 receptor agonists improve metabolic and liver outcomes in MASLD.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)", "glycan_involvement": "Glycosylation may modulate PNPLA3 stability and activity.", "mechanism": "PNPLA3 genetic variants increase risk and progression of MASLD.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12389333" }, { "confidence": "medium", "disease": "MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)", "glycan_involvement": "Glycosylation may affect TM6SF2 function in lipid metabolism.", "mechanism": "TM6SF2 variants predispose to hepatic steatosis and fibrosis.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12389333" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "SR-A1 is a glycoprotein; glycosylation affects ligand binding and stability.", "mechanism": "Promotes macrophage uptake of modified LDL, leading to foam cell formation and plaque progression.", "protein": "SR-A1", "relationship_type": "causal", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CD36 glycosylation modulates receptor function and trafficking.", "mechanism": "Mediates unregulated oxLDL uptake in macrophages, driving foam cell formation and inflammation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LOX-1 is a glycoprotein; glycosylation required for surface expression.", "mechanism": "Upregulated in inflammation, increases oxLDL uptake and foam cell formation.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "causal", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "SR-B1 glycosylation influences receptor stability and cholesterol transport.", "mechanism": "Facilitates cholesterol efflux from macrophages to HDL, reducing foam cell burden.", "protein": "SR-B1", "relationship_type": "protective", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ABCA1 is glycosylated; glycosylation affects trafficking and function.", "mechanism": "Promotes cholesterol efflux to apoA-1, initiating reverse cholesterol transport.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ABCG1 glycosylation modulates transporter activity.", "mechanism": "Mediates cholesterol efflux to HDL, limiting foam cell formation.", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "protective", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "TLR4 N-glycosylation is essential for ligand recognition and signaling.", "mechanism": "Activation by oxLDL triggers pro-inflammatory signaling and upregulates CD36/SR-A1, promoting lipid accumulation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12389334" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ICAM-1 glycosylation regulates cell-cell interactions.", "mechanism": "Upregulated in endothelial cells during inflammation, mediates monocyte adhesion and recruitment.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389334" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "VCAM-1 glycosylation modulates adhesion properties.", "mechanism": "Facilitates monocyte adhesion to endothelium, promoting lesion initiation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389334" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ACAT1 is glycosylated, which may affect enzyme localization and activity.", "mechanism": "Catalyzes cholesterol esterification in macrophages; inhibition reduces foam cell formation.", "protein": "ACAT1", "protein_enriched": { "function": "Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:16154994, PubMed:16647063, PubMed:32433613, PubMed:32433614, PubMed:32944968, Pub", "gene_name": "SOAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35610" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389334" }, { "confidence": "high", "disease": "Streptococcus suis infection", "glycan_involvement": "CPS is a glycan-rich surface structure; glycosylation is essential for antigenicity and virulence.", "mechanism": "CPS is the major virulence factor mediating immune evasion and serotype classification.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "high", "disease": "Meningitis", "glycan_involvement": "Glycosylation of CPS is critical for immune evasion and blood-brain barrier crossing.", "mechanism": "CPS enables S. suis to evade host immunity, facilitating CNS invasion.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycan structure of CPS is key for resistance to host defenses.", "mechanism": "CPS protects bacteria from phagocytosis, promoting systemic infection.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Endocarditis", "glycan_involvement": "Glycosylation of CPS facilitates tissue colonization.", "mechanism": "CPS mediates adhesion and persistence in cardiac tissue.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Glycan-rich CPS is essential for CNS invasion.", "mechanism": "CPS-mediated immune evasion allows CNS infection, leading to sequelae like hearing loss.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Streptococcus suis infection", "glycan_involvement": "Glycosylation may affect MRP stability and immune recognition.", "mechanism": "MRP is a virulence-associated glycoprotein used for strain typing and virulence assessment.", "protein": "Muramidase-released protein (MRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Streptococcus suis infection", "glycan_involvement": "Pilus glycosylation may modulate host interaction and immune evasion.", "mechanism": "Pilus proteins mediate adhesion to host tissues, contributing to colonization and infection.", "protein": "Pilus proteins (srtG, etc.)", "relationship_type": "causal", "source_pmcid": "PMC12389401" }, { "confidence": "high", "disease": "Streptococcus suis infection", "glycan_involvement": "Targeting glycan epitopes of CPS for vaccine development.", "mechanism": "CPS is proposed as a vaccine antigen and for molecular typing.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Streptococcus suis infection", "glycan_involvement": "Glycosylation sites may be targeted for immune intervention.", "mechanism": "Pilus islands are considered for vaccine and drug targeting.", "protein": "Pilus proteins (srtG, etc.)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389401" }, { "confidence": "medium", "disease": "Streptococcus suis infection", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "MRP is a candidate for diagnostic and vaccine development.", "protein": "Muramidase-released protein (MRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389401" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "Glycosylation of GPC is required for proper folding, viral infectivity, and immune evasion.", "mechanism": "The GPC mediates viral entry, fusion, and infectivity, essential for CCHFV pathogenesis.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389410" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "Anti-GPC IgM/IgG antibodies are detected in patient sera and used for diagnosis.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389410" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "Glycosylation sites may influence vaccine efficacy and immune response.", "mechanism": "GPC is a target for vaccine development and antiviral strategies.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389410" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever", "glycan_involvement": "Glycosylation near fusion domains may modulate fusion efficiency.", "mechanism": "K517 variant in GPC is associated with enhanced viral fusion and infectivity in vitro, possibly impacting disease severity.", "protein": "CCHFV glycoprotein precursor (GPC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389410" }, { "confidence": "high", "disease": "Multidrug resistance", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Effluxes chemotherapeutic drugs, causing resistance; nanoparticle delivery can bypass P-gp-mediated efflux.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation affects receptor binding and targeting.", "mechanism": "Transferrin receptor is overexpressed in tumors; transferrin-functionalized nanoparticles target cancer cells.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation modulates receptor interaction and stability.", "mechanism": "Lactoferrin-conjugated nanoparticles enhance delivery and uptake in aggressive breast cancer cells.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation critical for receptor function and ligand binding.", "mechanism": "Folate receptor is overexpressed in tumors; folic acid-functionalized nanoparticles selectively target cancer cells.", "protein": "Folate receptor", "protein_enriched": { "function": "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, P", "gene_name": "FOLR1", "glycan_count": 68, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G23294PN", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G59536GA", "G60177UT", "G62765YT", "G65184UU", "G66088HZ", "G66163OV", "G68490OW", "G70101JE", "G71051TA", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90382BL", "G92135MA", "G95133RI", "G98611JV", "G99668VU", "G92062TF", "G04657PL", "G05049YU", "G07755XJ", "G10819WX", "G11870QZ", "G13131HA", "G15169WU", "G15664MX", "G20210JR", "G23719VF", "G23984SE", "G31852PQ", "G36379GD", "G42124LM", "G45504EY", "G62894KT", "G70619PT", "G77547TA", "G84225JN", "G90659AW", "G95177YH", "G49108TO" ], "uniprot_id": "P15328" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect cell surface localization.", "mechanism": "AS1411 aptamer targets nucleolin on cancer cell surfaces for nanoparticle-mediated drug delivery.", "protein": "Nucleolin", "protein_enriched": { "function": "Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding t", "gene_name": "NCL", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G18647XP", "G37399XV", "G41247ZX", "G68735SN" ], "uniprot_id": "P19338" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "VEGF promotes angiogenesis in tumors; phytochemicals inhibit VEGF expression.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "EGFR signaling drives tumor growth; phytochemicals modulate EGFR pathways.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "TNF-alpha mediates inflammatory response; phytochemicals modulate TNF-alpha signaling.", "protein": "TNF-alpha", "relationship_type": "causal", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation modulates STAT3 activity.", "mechanism": "STAT3 promotes tumor survival and proliferation; phytochemicals inhibit STAT3 signaling.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389418" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Potential glycosylation may affect stability.", "mechanism": "NQO1 overexpression in tumors enables selective activation of \u03b2-Lapachone for cancer cell death.", "protein": "NQO1", "protein_enriched": { "function": "Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons ar", "gene_name": "NQO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15559" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389418" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor binding.", "mechanism": "Promotes hepatic inflammation and progression of steatosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects TGF-\u03b2 stability and signaling.", "mechanism": "Drives fibrogenesis in liver during NAFLD progression.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation regulates IL-6 receptor interactions.", "mechanism": "Induces hepatic inflammation and insulin resistance.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation influences albumin stability and half-life.", "mechanism": "Serum albumin levels reflect liver synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects enzyme activity and localization.", "mechanism": "Upregulation enhances bilirubin clearance and detoxification.", "protein": "CYP3A1", "relationship_type": "protective", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may regulate receptor function.", "mechanism": "Activation promotes hepatic detoxification and bilirubin metabolism.", "protein": "CAR", "relationship_type": "protective", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for enzymatic activity.", "mechanism": "Increased activity clears bilirubin, linked to metabolic health.", "protein": "UGT1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates transcriptional activity.", "mechanism": "Upregulation increases de novo lipogenesis and hepatic fat accumulation.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects cytokine stability and signaling.", "mechanism": "Contributes to hepatic inflammation.", "protein": "IL-2", "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Promotes recruitment of inflammatory cells to liver.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "causal", "source_pmcid": "PMC12389473" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "PCSK9 is a glycoprotein; glycosylation is required for secretion and function.", "mechanism": "PCSK9 promotes degradation of LDLR, reducing LDL-C clearance and raising plasma cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389475" }, { "confidence": "high", "disease": "Familial hypercholesterolemia (FH)", "glycan_involvement": "Glycosylation affects PCSK9 stability and secretion.", "mechanism": "Gain-of-function mutations in PCSK9 cause FH; PCSK9 inhibition lowers LDL-C in FH.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "N-glycosylation required for LDLR folding, trafficking, and function.", "mechanism": "LDLR mediates LDL-C clearance; loss-of-function mutations cause hypercholesterolemia.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "high", "disease": "Familial hypercholesterolemia (FH)", "glycan_involvement": "N-glycosylation critical for LDLR stability and cell surface expression.", "mechanism": "Mutations in LDLR gene cause FH; therapies upregulate LDLR to treat FH.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation modulates PCSK9 function.", "mechanism": "PCSK9 inhibition reduces LDL-C and ASCVD risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "ANGPTL3 is a glycoprotein; glycosylation required for secretion.", "mechanism": "ANGPTL3 inhibition lowers LDL-C and triglycerides, especially in patients with impaired LDLR.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "ApoB-100 is glycosylated; glycosylation affects LDL structure and receptor interaction.", "mechanism": "ApoB-100 is essential for LDL particle formation and LDLR binding.", "protein": "ApoB-100", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "ASGPR is a glycoprotein; recognizes glycan ligands for targeted delivery.", "mechanism": "ASGPR mediates hepatocyte uptake of GalNAc-conjugated siRNA (inclisiran) for PCSK9 silencing.", "protein": "ASGPR", "relationship_type": "therapeutic_target (drug delivery)", "source_pmcid": "PMC12389475" }, { "confidence": "medium", "disease": "Elevated lipoprotein(a) [Lp(a)]", "glycan_involvement": "Indirect; PCSK9 glycosylation not directly linked to Lp(a) effect.", "mechanism": "PCSK9 inhibitors modestly reduce Lp(a) levels, lowering cardiovascular risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "medium", "disease": "Statin intolerance", "glycan_involvement": "N-glycosylation required for LDLR function.", "mechanism": "Non-statin therapies (PCSK9 inhibitors, inclisiran) upregulate LDLR to lower LDL-C in statin-intolerant patients.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389475" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "NS fractions inhibit TNF-\u03b1, reducing inflammation and tissue damage in CCl4-induced liver injury.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "COX-2 is N-glycosylated, which regulates its stability and activity.", "mechanism": "NS fractions inhibit COX-2, decreasing inflammatory response in liver tissue.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "CYP2E1 is glycosylated, affecting its localization and function.", "mechanism": "CYP2E1 metabolizes CCl4 to toxic radicals causing liver damage; NS fractions inhibit CYP2E1, reducing toxicity.", "protein": "CYP P450 2E1", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and red", "gene_name": "CYP2E1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05181" }, "relationship_type": "causal", "source_pmcid": "PMC12389490" }, { "confidence": "medium", "disease": "Kidney injury (nephrotoxicity)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 bioactivity.", "mechanism": "Inhibition of TNF-\u03b1 by NS fractions reduces kidney inflammation and damage.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389490" }, { "confidence": "medium", "disease": "Kidney injury (nephrotoxicity)", "glycan_involvement": "N-glycosylation modulates COX-2 function.", "mechanism": "COX-2 inhibition by NS fractions reduces renal inflammation.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Kidney injury (nephrotoxicity)", "glycan_involvement": "Albumin glycosylation affects renal handling and filtration.", "mechanism": "Elevated urinary albumin indicates glomerular damage; NS fractions reduce albuminuria.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "ALT is glycosylated, influencing serum stability.", "mechanism": "ALT elevation reflects hepatocyte injury; NS fractions normalize ALT.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "AST glycosylation affects its serum half-life.", "mechanism": "AST elevation indicates liver cell damage; NS fractions reduce AST.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12389490" }, { "confidence": "high", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "ALP is highly glycosylated, which modulates its activity and clearance.", "mechanism": "ALP elevation signals cholestasis or liver injury; NS fractions lower ALP.", "protein": "ALP (Alkaline Phosphatase)", "relationship_type": "biomarker", "source_pmcid": "PMC12389490" }, { "confidence": "medium", "disease": "Liver injury (hepatotoxicity)", "glycan_involvement": "Albumin glycosylation influences bilirubin binding and transport.", "mechanism": "Elevated bilirubin reflects impaired hepatic clearance; NS fractions reduce direct bilirubin.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12389490" }, { "confidence": "medium", "disease": "Pediatric Asthma", "glycan_involvement": "Glycosylation is essential for lactoferrin's stability and immune-modulatory function.", "mechanism": "Lactoferrin modulates allergic responses by regulating Th2 cytokines and suppressing mast cell degranulation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389496" }, { "confidence": "medium", "disease": "Allergic Rhinitis", "glycan_involvement": "Glycosylation affects lactoferrin's mucosal binding and immune activity.", "mechanism": "Lactoferrin reduces nasal inflammation and symptoms via antioxidant and anti-inflammatory effects.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389496" }, { "confidence": "high", "disease": "Allergic Rhinitis", "glycan_involvement": "O-glycosylation of MUC5AC is critical for mucus properties and allergen trapping.", "mechanism": "Zinc depletion induces MUC5AC expression, leading to mucus hypersecretion in nasal mucosa.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389496" }, { "confidence": "high", "disease": "Pediatric Asthma", "glycan_involvement": "IgE glycosylation modulates receptor binding and effector function.", "mechanism": "Zinc deficiency skews immune response toward Th2, increasing IgE production and allergic inflammation.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12389496" }, { "confidence": "high", "disease": "Allergic Rhinitis", "glycan_involvement": "IgE glycosylation affects allergen recognition and immune activation.", "mechanism": "Zinc deficiency increases total and allergen-specific IgE, exacerbating allergic symptoms.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12389496" }, { "confidence": "medium", "disease": "Pediatric Asthma", "glycan_involvement": "N-glycosylation is required for E-cadherin's cell adhesion and barrier function.", "mechanism": "Zinc maintains epithelial barrier by stabilizing E-cadherin; deficiency leads to barrier dysfunction.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12389496" }, { "confidence": "medium", "disease": "Pediatric Asthma", "glycan_involvement": "Glycosylation modulates claudin localization and function.", "mechanism": "Zinc supports tight junction integrity via claudin stabilization; deficiency increases permeability.", "protein": "Claudins", "relationship_type": "protective", "source_pmcid": "PMC12389496" }, { "confidence": "medium", "disease": "Pediatric Asthma", "glycan_involvement": "Glycosylation is important for occludin's membrane localization.", "mechanism": "Zinc preserves tight junctions by stabilizing occludin; deficiency disrupts epithelial barrier.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12389496" }, { "confidence": "low", "disease": "Allergic Rhinitis", "glycan_involvement": "Not a classical glycoprotein, but may interact with glycosylated proteins in mucosa.", "mechanism": "Zinc induces metallothionein expression, which buffers oxidative stress and supports epithelial repair.", "protein": "Metallothionein", "relationship_type": "protective", "source_pmcid": "PMC12389496" }, { "confidence": "high", "disease": "Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)", "glycan_involvement": "O-glycosylation of MUC5AC is essential for mucus viscosity and disease pathology.", "mechanism": "Zinc depletion increases MUC5AC expression, contributing to mucus hypersecretion and polyp formation.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389496" }, { "confidence": "high", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in MetS, reflecting chronic low-grade inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389504" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates fibrinogen's clotting properties.", "mechanism": "Elevated fibrinogen increases clot formation and risk of thrombosis in MetS and obesity.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation critical for vWF multimerization and function.", "mechanism": "vWF is increased in diabetes and MetS, promoting platelet adhesion and atherothrombosis.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ligand binding and trafficking.", "mechanism": "P-selectin mediates leukocyte and platelet adhesion, promoting vascular inflammation and plaque formation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Inflammation (chronic)", "glycan_involvement": "N-glycosylation modulates cell surface expression and function.", "mechanism": "ICAM-1 is upregulated in IR and obesity, facilitating leukocyte adhesion and vascular inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects ligand binding.", "mechanism": "VCAM-1 promotes monocyte adhesion to endothelium, contributing to plaque development.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for procoagulant activity.", "mechanism": "TF expression is increased by inflammation (e.g., TNF-\u03b1), initiating coagulation cascade.", "protein": "Tissue factor (TF)", "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "high", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "PAI-1 is elevated in obesity and MetS, inhibiting fibrinolysis and promoting thrombosis.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Leptin is glycosylated, which affects its secretion and receptor binding.", "mechanism": "Leptin increases platelet aggregation and CRP, worsening endothelial dysfunction.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "medium", "disease": "Inflammation (chronic)", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Resistin promotes endothelial dysfunction and inflammation via NF-\u03baB and MAPK pathways.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC12389504" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "CRP glycosylation modulates its stability and function in inflammation.", "mechanism": "CRP is elevated in CVD and correlates with inflammation and nutritional risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "N-glycosylation affects albumin half-life and function.", "mechanism": "Low serum albumin indicates poor nutritional status and is associated with worse outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Glycation (not classical glycosylation) is relevant in diabetes.", "mechanism": "Low hemoglobin reflects anemia secondary to malnutrition.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "LDL glycoprotein components influence receptor binding and clearance.", "mechanism": "Elevated LDL is a risk factor for atherosclerosis and CVD.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "HDL glycoprotein glycosylation modulates anti-inflammatory properties.", "mechanism": "HDL is protective against CVD via reverse cholesterol transport.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "N-glycosylation affects transferrin stability and iron binding.", "mechanism": "Low transferrin is a marker of protein-energy malnutrition.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Fc N-glycosylation modulates immune effector functions.", "mechanism": "Altered IgG glycosylation reflects systemic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation affects fibrinogen clotting properties.", "mechanism": "Elevated fibrinogen is associated with increased CVD risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Highly glycosylated; glycan changes reflect inflammatory state.", "mechanism": "Levels rise in acute and chronic inflammation, including CVD.", "protein": "Alpha-1-acid glycoprotein (Orosomucoid)", "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation modulates antioxidant and immune functions.", "mechanism": "Haptoglobin levels and glycoforms are altered in CVD and inflammation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389558" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and trafficking.", "mechanism": "APP is abnormally processed to generate A\u03b2 peptides, which aggregate into plaques central to AD pathogenesis.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Derived from glycosylated APP; glycosylation state influences aggregation.", "mechanism": "A\u03b2 aggregates form plaques, causing synaptic dysfunction, neurotoxicity, and neuroinflammation.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12389568" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-GlcNAcylation of tau inhibits its phosphorylation and aggregation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, correlating with cognitive decline.", "protein": "Tau protein", "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12389568" }, { "confidence": "high", "disease": "Sporadic Alzheimer's disease", "glycan_involvement": "APOE is glycosylated; glycosylation may affect lipid binding and A\u03b2 clearance.", "mechanism": "APOE \u03b54 allele increases A\u03b2 deposition and AD risk; gene therapy targeting APOE2 is protective.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "MMPs are glycoproteins; glycosylation affects secretion and activity.", "mechanism": "MMPs modulate extracellular matrix and may influence A\u03b2 clearance and neuroinflammation.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "NLRP3 is glycosylated; glycosylation may regulate inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation by A\u03b2 promotes neuroinflammation and amyloid pathology.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "BDNF is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "BDNF supports neuronal survival and synaptic plasticity; gene therapy aims to restore BDNF in AD.", "protein": "BDNF", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12389568" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TrkB is N-glycosylated; glycosylation is critical for cell surface expression.", "mechanism": "TrkB mediates BDNF signaling; activation promotes neurogenesis and cognitive function.", "protein": "TrkB (NTRK2)", "protein_enriched": { "function": "Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiati", "gene_name": "NTRK2", "glycan_count": 22, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G40574BA", "G41247ZX", "G43089EG", "G48414YA", "G62765YT", "G80920RR", "G06356OH", "G00912UN", "G04657PL", "G64394MX", "G72291OX", "G47518TP", "G20312EM", "G82463GQ", "G14796IU", "G33791AF", "G37399XV", "G38663NM", "G49108TO" ], "uniprot_id": "Q16620" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "high", "disease": "Tauopathy", "glycan_involvement": "Directly regulates O-GlcNAc modification of tau.", "mechanism": "Inhibition increases tau O-GlcNAcylation, reducing tau phosphorylation and aggregation.", "protein": "O-GlcNAcase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; O-GlcNAcylation of tau competes with GSK-3\u03b2-mediated phosphorylation.", "mechanism": "GSK-3\u03b2 hyperphosphorylates tau, promoting tangle formation.", "protein": "Glycogen synthase kinase-3 beta (GSK-3\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389568" }, { "confidence": "high", "disease": "Drug-resistant melanoma", "glycan_involvement": "Glycosylation is essential for P-gp folding, stability, and membrane localization.", "mechanism": "P-gp mediates efflux of paclitaxel, reducing intracellular drug accumulation and contributing to chemotherapy resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389586" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "N-glycosylation required for functional expression.", "mechanism": "Overexpression of P-gp leads to decreased efficacy of chemotherapeutics like paclitaxel.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12389586" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "MMP-9 degrades extracellular matrix, promoting tumor cell migration and metastasis.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12389586" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "N-glycosylation modulates enzymatic activity.", "mechanism": "Upregulated MMP-9 correlates with increased invasiveness and poor prognosis.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12389586" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation influences stability and inhibitory function.", "mechanism": "TIMP-2 inhibits MMP-9, suppressing angiogenesis, metastasis, and proliferation.", "protein": "Tissue inhibitor of metalloproteinases-2 (TIMP-2)", "relationship_type": "protective", "source_pmcid": "PMC12389586" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Used in detection and imaging of melanoma cells.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389586" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects solubility and stability.", "mechanism": "Used as a carrier protein in experimental assays.", "protein": "Bovine serum albumin (BSA)", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typicall", "gene_name": "ALB", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02769" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389586" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "N-glycosylation required for drug efflux function.", "mechanism": "Inhibition of P-gp increases paclitaxel retention and efficacy in metastatic melanoma.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389586" }, { "confidence": "medium", "disease": "Drug-resistant melanoma", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "PTX-induced NF-\u03baB activation upregulates MMP-9, promoting resistance and metastasis.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12389586" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "Glycosylation affects inhibitory function.", "mechanism": "Upregulation of TIMP-2 inhibits MMP-9, reducing metastatic potential.", "protein": "Tissue inhibitor of metalloproteinases-2 (TIMP-2)", "relationship_type": "protective", "source_pmcid": "PMC12389586" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates Spike binding and viral entry.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2; downregulation by SG reduces viral infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389595" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation shields epitopes and affects ACE2 interaction.", "mechanism": "Spike S1 binds ACE2 to mediate viral entry and triggers inflammation.", "protein": "SARS-CoV-2 Spike protein (S1)", "relationship_type": "causal", "source_pmcid": "PMC12389595" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation can regulate NF-\u03baB pathway activation.", "mechanism": "NF-\u03baB activation drives inflammatory cytokine production; SG inhibits its phosphorylation.", "protein": "NF-\u03baB p65 (RELA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389595" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "IL-6 glycosylation affects secretion and stability.", "mechanism": "Elevated IL-6 correlates with COVID-19 severity and mortality; SG reduces IL-6 secretion.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389595" }, { "confidence": "medium", "disease": "Microangiopathy", "glycan_involvement": "ACE2 glycosylation influences vascular localization and function.", "mechanism": "ACE2 dysregulation by SARS-CoV-2 contributes to endothelial damage and microangiopathy.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389595" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TNF glycosylation modulates receptor binding and activity.", "mechanism": "TNF is upregulated in COVID-19 and contributes to inflammation.", "protein": "TNF", "relationship_type": "biomarker", "source_pmcid": "PMC12389595" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect TP53 stability and function.", "mechanism": "TP53 is implicated in cellular stress responses during infection.", "protein": "TP53", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389595" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation modulates NF-\u03baB signaling in gut inflammation.", "mechanism": "NF-\u03baB pathway activation is central to IBD pathogenesis; SG targets this pathway.", "protein": "NF-\u03baB p65 (RELA)", "relationship_type": "causal", "source_pmcid": "PMC12389595" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-6 glycosylation affects its bioactivity.", "mechanism": "SG inhibits IL-6 secretion, reducing COVID-19-associated inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389595" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "Spike glycosylation modulates immune recognition and cytokine induction.", "mechanism": "Spike S1 triggers NF-\u03baB activation and cytokine release.", "protein": "SARS-CoV-2 Spike protein (S1)", "relationship_type": "causal", "source_pmcid": "PMC12389595" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes and affect immune recognition.", "mechanism": "CAR-T cells target gp120 to eliminate HIV-infected cells.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Epstein\u2013Barr virus (EBV) infection", "glycan_involvement": "gp350 is a glycoprotein; glycosylation affects antibody binding and immune evasion.", "mechanism": "CAR-T cells target gp350 to control EBV spread and EBV-associated lymphomas.", "protein": "gp350", "protein_enriched": { "function": "Plays an essential role in virion nuclear egress, the first step of virion release from infected cell. Within the host nucleus, NEC1 interacts with the newly formed capsid through the vertexes and dir", "gene_name": "NEC2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03185" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Cytomegalovirus (CMV) infection", "glycan_involvement": "Glycoprotein B is N-glycosylated, influencing viral entry and immune recognition.", "mechanism": "CAR-T cells target glycoprotein B to eliminate CMV-infected cells.", "protein": "glycoprotein B", "protein_enriched": { "function": "Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate toge", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 18, "glytoucan_ids": [], "uniprot_id": "P13201" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "HBsAg is glycosylated; glycosylation modulates antigenicity and immune escape.", "mechanism": "CAR-T cells target HBsAg to eliminate HBV-infected hepatocytes.", "protein": "HBsAg (S and L proteins)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "E2 is highly glycosylated, affecting immune evasion and receptor binding.", "mechanism": "CAR-T cells target E2 glycoprotein to kill HCV-infected cells.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is extensively N-glycosylated, influencing immune recognition and viral entry.", "mechanism": "CAR-T/NK/macrophage cells target S protein to eliminate SARS-CoV-2-infected cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Invasive pulmonary aspergillosis", "glycan_involvement": "\u03b2-glucan is a fungal polysaccharide; not glycosylated protein but a glycan target.", "mechanism": "Dectin-1 CAR-T cells target \u03b2-glucan in Aspergillus cell wall to inhibit fungal growth.", "protein": "\u03b2-glucan", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Cryptococcosis", "glycan_involvement": "GXM is a polysaccharide capsule; glycan structure is essential for virulence.", "mechanism": "GXMR-CAR-T cells target GXM in Cryptococcus capsule to reduce fungal burden.", "protein": "Glucuronoxylomannan (GXM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "medium", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "LMP1 is a membrane protein with potential glycosylation; role in immune evasion.", "mechanism": "CAR-T cells target LMP1 to kill EBV-positive carcinoma cells.", "protein": "LMP1", "protein_enriched": { "function": "Acts as a CD40 functional homolog to prevent apoptosis of infected B-lymphocytes and drive their proliferation. Functions as a constitutively active tumor necrosis factor receptor that induces the act", "gene_name": "LMP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03230" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Env is heavily glycosylated; glycans modulate antibody access and immune escape.", "mechanism": "BNAb-derived CAR-T cells target conserved Env regions to suppress HIV replication.", "protein": "Env glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389600" }, { "confidence": "high", "disease": "Chickenpox", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Essential for VZV entry and membrane fusion in host cells.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Chickenpox", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Promotes VZV infection by interacting with host IDE.", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Chickenpox", "glycan_involvement": "Glycosylation supports membrane fusion activity.", "mechanism": "Required for VZV entry into host cells.", "protein": "Glycoprotein H (gH)", "protein_enriched": { "function": "Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional re", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09265" }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Chickenpox", "glycan_involvement": "Glycosylation stabilizes gH/gL complex.", "mechanism": "Forms complex with gH for viral entry.", "protein": "Glycoprotein L (gL)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09266" }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "medium", "disease": "Breakthrough varicella infection", "glycan_involvement": "Glycosylation affects skin tropism and immune evasion.", "mechanism": "Important for VZV proliferation in skin cells; differences in gC may affect vaccine strain virulence.", "protein": "Glycoprotein C (gC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Latent VZV infection", "glycan_involvement": "Glycosylation of gB and MAG mediates binding and fusion.", "mechanism": "gB interacts with MAG to mediate VZV entry into neurons for latency.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Latent VZV infection", "glycan_involvement": "MAG is a sialylated glycoprotein; glycan moieties are critical for VZV binding.", "mechanism": "MAG acts as neuronal entry receptor for VZV via gB binding, enabling latency.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "medium", "disease": "Shingles (Herpes zoster)", "glycan_involvement": "Glycosylation required for efficient viral spread.", "mechanism": "Reactivation from latency involves gB-mediated neuronal egress.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may modulate neurotropism.", "mechanism": "gE-mediated infection of neuronal cells may contribute to CNS involvement.", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "medium", "disease": "Acute retinal necrosis", "glycan_involvement": "Glycosylation may affect tissue tropism.", "mechanism": "gB enables VZV entry into retinal cells, leading to necrosis.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389673" }, { "confidence": "high", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycosylation of E2 is essential for proper folding, antigenicity, and immunogenicity.", "mechanism": "Target of neutralizing antibodies; subunit and chimeric vaccines based on E2 induce protective immunity.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "Transplacental CSFV infection", "glycan_involvement": "Glycosylation affects E2's immunogenicity and vaccine efficacy.", "mechanism": "E2-based vaccines aim to prevent vertical transmission by eliciting neutralizing antibodies.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389750" }, { "confidence": "medium", "disease": "Persistent CSFV infection", "glycan_involvement": "Glycans on E2 shield epitopes from immune recognition.", "mechanism": "E2 mediates viral entry and immune evasion, contributing to persistent infection in fetuses.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC12389750" }, { "confidence": "medium", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycosylation may affect E1 structure and immunogenicity.", "mechanism": "E1 is modified in FlagT4G vaccine (FLAG epitope insertion) for DIVA capability.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389750" }, { "confidence": "medium", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycosylation required for CD154 function and stability.", "mechanism": "Used as an immunostimulatory adjuvant in E2 subunit vaccines to enhance early protection.", "protein": "CD154 (CD40 ligand)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycosylation influences epitope presentation in diagnostic assays.", "mechanism": "E2-specific antibodies serve as a biomarker for infection/vaccination status (DIVA).", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389750" }, { "confidence": "medium", "disease": "Transplacental CSFV infection", "glycan_involvement": "Glycosylation affects IFN-\u03b1 stability and bioactivity.", "mechanism": "Elevated IFN-\u03b1 in fetuses indicates active CSFV infection and immune activation.", "protein": "IFN-\u03b1", "protein_enriched": { "function": "Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase", "gene_name": "IFNA7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01567" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycosylation required for immunogenic conformation.", "mechanism": "E2-based vaccines (e.g., FlagT4G) induce rapid, robust neutralizing antibody responses conferring protection.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "protective", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "Transplacental CSFV infection", "glycan_involvement": "Glycosylation critical for vaccine efficacy in preventing vertical transmission.", "mechanism": "FlagT4G vaccine prevents fetal infection by inducing maternal immunity targeting E2.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "protective", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "Classical Swine Fever (CSF)", "glycan_involvement": "Glycan modifications may influence DIVA assay specificity.", "mechanism": "Epitope deletion in E2 (FlagT4G) enables serological differentiation of infected vs. vaccinated animals.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "DIVA marker", "source_pmcid": "PMC12389750" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2 binding, initiating infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector functions and antibody stability.", "mechanism": "Anti-Spike IgG titers reflect humoral immune response and correlate with protection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "Breakthrough infection", "glycan_involvement": "Altered glycosylation sites in variants affect antibody binding.", "mechanism": "Spike glycoprotein variants (e.g., Omicron) evade neutralizing antibodies, leading to breakthrough.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "Reduced IFN-\u03b3 levels post-vaccination in older adults indicate diminished cellular immunity.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "Altered glycosylation impacts T cell receptor signaling and function.", "mechanism": "Age-related decline in CD4+ T cell activation and cytokine production impairs vaccine response.", "protein": "CD4+ T cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "Glycosylation modulates T cell activation and cytotoxicity.", "mechanism": "Reduced CD8+ na\u00efve T cell repertoire limits memory response to vaccination in elderly.", "protein": "CD8+ T cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Surface glycoprotein glycosylation regulates cell-cell interactions.", "mechanism": "Follicular helper T cells promote germinal center formation and antibody affinity maturation.", "protein": "Follicular helper T cell glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12389793" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Anti-N IgG response is used to distinguish infection from vaccination.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates Spike binding affinity.", "mechanism": "ACE2 glycoprotein is the entry receptor for Spike protein, enabling viral infection.", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "medium", "disease": "Immunosenescence", "glycan_involvement": "Glycosylation affects cytokine secretion and receptor binding.", "mechanism": "Reduced IL-17 impairs B cell survival and antibody production in aging.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal", "source_pmcid": "PMC12389793" }, { "confidence": "high", "disease": "Cowpox", "glycan_involvement": "Glycosylation required for receptor interaction and immune evasion.", "mechanism": "Mediates CPXV entry into dendritic cells via receptor binding, initiating infection.", "protein": "Hemagglutinin glycoprotein (CPXV)", "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and mediate receptor binding.", "mechanism": "Facilitates viral entry into DCs via DC-SIGN, furin, Neuropilin-1, and CD147.", "protein": "Spike protein (SARS-CoV/SARS-CoV-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Recognizes high-mannose glycans on viral spike protein.", "mechanism": "Acts as an alternative receptor for SARS-CoV-2 spike protein on DCs, mediating uptake and immune activation.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389827" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor function and spike binding.", "mechanism": "Alternative entry receptor for SARS-CoV-2 spike protein on DCs.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may affect ligand binding and immune modulation.", "mechanism": "Suppresses T-cell activation by binding CD80/CD86, blocking co-stimulation and promoting T-cell exhaustion.", "protein": "M2 protein (MPXV)", "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "Monkeypox", "glycan_involvement": "Glycosylation stabilizes receptor structure and ligand binding.", "mechanism": "Acts as a decoy TNF receptor, neutralizing TNF-\u03b1 and disrupting immune activation.", "protein": "CrmB (MPXV)", "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may influence protein stability and immune evasion.", "mechanism": "Binds dsRNA, sequestering it from PRRs and inhibiting IFN production.", "protein": "F3 protein (MPXV)", "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "Vaccine response failure", "glycan_involvement": "N-glycans mask neutralizing epitopes.", "mechanism": "Glycan shield on spike protein impairs antibody recognition, reducing vaccine efficacy.", "protein": "Spike protein (SARS-CoV/SARS-CoV-2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor-ligand interaction.", "mechanism": "Facilitates SARS-CoV-2 entry into DCs via S1 spike subunit binding.", "protein": "Neuropilin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389827" }, { "confidence": "medium", "disease": "T-cell exhaustion", "glycan_involvement": "Glycosylation may affect PD-L1 interaction.", "mechanism": "Potentiates PD-L1 signaling, exacerbating T-cell exhaustion and immune dysfunction.", "protein": "M2 protein (MPXV)", "relationship_type": "causal", "source_pmcid": "PMC12389827" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is heavily glycosylated, which shields epitopes and modulates immune recognition.", "mechanism": "Spike mediates viral entry via ACE2 binding; initiates infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "SARS-CoV-2 breakthrough infection", "glycan_involvement": "Variant-specific glycosylation patterns alter antibody accessibility.", "mechanism": "Spike mutations (esp. Omicron) reduce neutralization by vaccine-induced antibodies.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG Fc glycosylation modulates effector functions and antibody stability.", "mechanism": "Anti-Spike IgG neutralizes virus, reducing infection risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "SARS-CoV-2 breakthrough infection", "glycan_involvement": "Glycosylation affects IgG half-life and immune activation.", "mechanism": "Low anti-Spike IgG titers correlate with increased breakthrough infection risk in KTRs.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "RBD glycosylation can mask epitopes and affect antibody binding.", "mechanism": "RBD is the main target for neutralizing antibodies; vaccine-induced immunity focuses on RBD.", "protein": "Receptor Binding Domain (RBD) of Spike", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389881" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation influences Spike binding affinity.", "mechanism": "ACE2 is the host receptor for Spike, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "Kidney transplant recipient immunosuppression", "glycan_involvement": "Spike glycosylation may further hinder immune recognition in immunosuppressed hosts.", "mechanism": "Reduced neutralizing antibody response to Spike in immunosuppressed KTRs.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12389881" }, { "confidence": "medium", "disease": "Kidney transplant recipient immunosuppression", "glycan_involvement": "Altered IgG glycosylation may occur under immunosuppression, affecting function.", "mechanism": "Lower IgG titers in KTRs on triple immunosuppression indicate poor vaccine response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "SARS-CoV-2 breakthrough infection", "glycan_involvement": "Spike glycosylation impacts neutralization sensitivity.", "mechanism": "Neutralizing antibody activity against Spike (WT, Delta, Omicron BA.2) predicts breakthrough risk.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12389881" }, { "confidence": "medium", "disease": "SARS-CoV-2 breakthrough infection", "glycan_involvement": "RBD glycosylation modulates antibody binding and neutralization.", "mechanism": "Non-neutralizing anti-RBD IgG before booster predicts better post-booster response.", "protein": "Receptor Binding Domain (RBD) of Spike", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389881" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Heavily glycosylated with up to 35 N-linked glycans, which mask epitopes and facilitate immune evasion.", "mechanism": "RSV G protein acts as an attachment factor, mediating viral entry into host cells.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Non-glycosylated form avoids glycan-mediated immune evasion and improves immunogenicity.", "mechanism": "Non-glycosylated recombinant G protein (BARS13 vaccine) induces anti-G IgG antibodies, neutralizing virus and preventing infection.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389995" }, { "confidence": "medium", "disease": "Vaccine-Enhanced Disease (VED)", "glycan_involvement": "Glycosylation masks epitopes, limiting effective immune response and increasing VED risk.", "mechanism": "Glycosylated forms of G protein implicated in VED risk due to immune evasion and poor antibody recognition.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Glycosylation state affects antigenicity and neutralizing antibody response.", "mechanism": "Prefusion F protein is targeted by licensed vaccines, eliciting strong neutralizing antibodies.", "protein": "RSV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Acute Lower Respiratory Tract Infection", "glycan_involvement": "Glycosylation enhances immune evasion, facilitating infection.", "mechanism": "G protein mediates viral attachment and infection of lower respiratory tract cells.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Acute Respiratory Infection", "glycan_involvement": "Non-glycosylated antigen improves antibody recognition and vaccine efficacy.", "mechanism": "BARS13 vaccine targeting non-glycosylated G protein induces protective immunity in elderly adults.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Non-glycosylated G protein improves reliability of antibody measurement.", "mechanism": "Anti-G IgG antibody levels serve as a biomarker for vaccine-induced immunity.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Absence of glycosylation enhances immunogenicity and protective antibody response.", "mechanism": "Vaccination with non-glycosylated G protein (BARS13) provides dose-dependent protection in elderly.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "protective", "source_pmcid": "PMC12389995" }, { "confidence": "medium", "disease": "Vaccine-Enhanced Disease (VED)", "glycan_involvement": "Avoidance of glycosylation minimizes immune evasion and VED risk.", "mechanism": "Non-glycosylated G protein vaccine formulation (BARS13) reduces risk of VED compared to glycosylated forms.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "protective", "source_pmcid": "PMC12389995" }, { "confidence": "medium", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Non-glycosylated recombinant protein preserves cysteine noose structure for antibody recognition.", "mechanism": "Conserved cysteine noose region in G protein is a target for neutralizing antibodies.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389995" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "E2 is a glycoprotein; glycosylation may affect receptor binding and immune evasion.", "mechanism": "Facilitates viral attachment and entry via direct interaction with host TLR4.", "protein": "CHIKV E2", "protein_enriched": { "function": "Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers ", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8JUX5" }, "relationship_type": "causal", "source_pmcid": "PMC12390013" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "E1 is a glycoprotein; glycosylation may modulate fusion efficiency and immune detection.", "mechanism": "Mediates viral membrane fusion and entry; mutations alter immune recognition.", "protein": "CHIKV E1", "relationship_type": "causal", "source_pmcid": "PMC12390013" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "TLR4 is glycosylated; glycosylation required for proper folding and ligand recognition.", "mechanism": "Facilitates early viral entry; inhibition reduces viral load and inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390013" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "TLR3 is glycosylated; glycosylation affects trafficking and ligand binding.", "mechanism": "Activation induces antiviral cytokines and IFN-\u03b2, limiting viral replication.", "protein": "TLR3", "protein_enriched": { "function": "Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a", "gene_name": "TLR3", "glycan_count": 35, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G00912UN", "G59626AS", "G62765YT", "G11314AS", "G23719VF", "G27947YN", "G31852PQ", "G41071NU", "G43669FQ", "G45395BF", "G47644PP", "G70232NH", "G80920RR", "G83460ZZ", "G92275SC", "G95865ZB", "G27058EU", "G37399XV", "G05962QB", "G69521XL", "G37818NZ", "G26436YP", "G22573RC", "G02815KT", "G11101UV", "G26377UA", "G28541PG", "G57489SP", "G63136LV", "G01650EU", "G41247ZX", "G59924QI", "G63041LO", "G96091TT", "G49108TO" ], "uniprot_id": "O15455" }, "relationship_type": "protective", "source_pmcid": "PMC12390013" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "TLR7 is glycosylated; glycosylation influences endosomal localization.", "mechanism": "Activation leads to IFN-I production; SNPs modulate susceptibility.", "protein": "TLR7", "relationship_type": "protective", "source_pmcid": "PMC12390013" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "TLR8 is glycosylated; glycosylation impacts receptor function.", "mechanism": "Activation induces antiviral cytokines; SNPs affect infection risk.", "protein": "TLR8", "protein_enriched": { "function": "Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation prod", "gene_name": "TLR8", "glycan_count": 17, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G79666IR", "G87123QX", "G07617FP", "G09724ZC", "G22573RC", "G22768VO", "G56014GC", "G80920RR", "G81315DD", "G83460ZZ", "G04657PL", "G27058EU", "G62765YT", "G10756ZZ", "G15664MX", "G55220VL", "G49108TO" ], "uniprot_id": "Q9NR97" }, "relationship_type": "protective", "source_pmcid": "PMC12390013" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "IFITM1 is glycosylated; glycosylation may affect antiviral activity.", "mechanism": "Overexpression inhibits CHIKV infection and upregulates TLRs.", "protein": "IFITM1", "protein_enriched": { "function": "IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endoso", "gene_name": "IFITM3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01628" }, "relationship_type": "protective", "source_pmcid": "PMC12390013" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Suppresses host IFN production and TLR signaling, promoting viral replication.", "protein": "CHIKV nsP2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12390013" }, { "confidence": "medium", "disease": "Chronic chikungunya arthritis", "glycan_involvement": "Glycosylation may affect immune evasion and chronicity.", "mechanism": "Persistent immune activation linked to E1-mediated viral persistence.", "protein": "CHIKV E1", "relationship_type": "causal", "source_pmcid": "PMC12390013" }, { "confidence": "medium", "disease": "Chikungunya-associated neurological complications", "glycan_involvement": "TLR4 glycosylation required for CNS signaling.", "mechanism": "Upregulation correlates with increased proinflammatory cytokines in CNS.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12390013" }, { "confidence": "high", "disease": "Hepatitis E", "glycan_involvement": "N-glycosylation of ORF2 modulates immune evasion and infectivity.", "mechanism": "HEV ORF2 glycoprotein forms the viral capsid, mediating host cell entry and immune recognition.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "medium", "disease": "Chronic Hepatitis E", "glycan_involvement": "Glycosylation affects chronicity and immune escape.", "mechanism": "Persistent infection in immunocompromised hosts is mediated by ORF2 glycoprotein.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may influence persistence and liver pathology.", "mechanism": "Chronic HEV infection can progress to cirrhosis, especially in immunocompromised individuals.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune detection.", "mechanism": "gp120 mediates HIV entry into host cells via CD4 and co-receptors.", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "N-glycosylation modulates fusion and immune evasion.", "mechanism": "gp41 mediates fusion of viral and host membranes.", "protein": "HIV Envelope Glycoprotein gp41", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "Glycosylated ORF2 is the antigenic target for antibody detection.", "mechanism": "Anti-HEV IgG/IgM seropositivity indicates HEV exposure in PLWH.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390178" }, { "confidence": "high", "disease": "Hepatitis E", "glycan_involvement": "Glycosylation affects antigenicity and ELISA performance.", "mechanism": "Detection of anti-HEV antibodies (IgG/IgM) is used for diagnosis.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390178" }, { "confidence": "medium", "disease": "HIV Infection", "glycan_involvement": "Glycosylation may influence immune evasion in co-infection.", "mechanism": "HEV co-infection is more frequent in advanced HIV (WHO III/IV), possibly due to immune dysfunction.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "causal", "source_pmcid": "PMC12390178" }, { "confidence": "medium", "disease": "Chronic Hepatitis E", "glycan_involvement": "Glycosylation impacts antibody recognition.", "mechanism": "Persistent anti-HEV IgG/IgM in PLWH may indicate chronic infection.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390178" }, { "confidence": "medium", "disease": "Hepatitis E", "glycan_involvement": "Proper glycosylation is required for immunogenicity.", "mechanism": "ORF2 is the target for HEV vaccine development.", "protein": "Hepatitis E Virus ORF2 Capsid Protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390178" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N- and O-glycosylation modulates antigenicity and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2 binding; target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity; purification via lectin affinity exploits glycan content.", "mechanism": "Vaccines displaying stabilized spike glycoprotein elicit neutralizing antibodies and protective immunity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects RBD structure and antibody accessibility.", "mechanism": "RBD is the main target of neutralizing antibodies; critical for ACE2 interaction.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390229" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NTD glycosylation influences immunodominance and antibody binding.", "mechanism": "NTD-specific antibodies are elicited but may be non-neutralizing; NTD domain used in nanoparticle vaccines.", "protein": "SARS-CoV-2 Spike NTD", "relationship_type": "biomarker", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "LuS itself is not glycosylated but enables display of glycosylated spike proteins.", "mechanism": "LuS serves as a nanoparticle scaffold for spike display, enhancing immunogenicity.", "protein": "Lumazine Synthase (LuS)", "protein_enriched": { "function": "Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate. This is the penultimate step in the biosynthesi", "gene_name": "ribH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O66529" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390229" }, { "confidence": "medium", "disease": "SARS-CoV-1 infection", "glycan_involvement": "Conserved glycosylation sites may contribute to cross-reactivity.", "mechanism": "Cross-neutralizing antibodies elicited by spike nanoparticle vaccines can neutralize SARS-CoV-1.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity.", "mechanism": "ACE2 is the host receptor for spike glycoprotein, mediating viral entry.", "protein": "Human ACE2", "relationship_type": "causal", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts antibody recognition and ELISA detection.", "mechanism": "Spike-specific IgG and IgA in serum and mucosa are biomarkers of vaccine-induced immunity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation maintains spike structure for mucosal immune recognition.", "mechanism": "Intranasal nanoparticle vaccines elicit mucosal IgA, potentially preventing infection and transmission.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation facilitates proper folding and multivalent antigen presentation.", "mechanism": "Multivalent display of spike on nanoparticles increases B cell activation and neutralizing antibody production.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390229" }, { "confidence": "high", "disease": "Herpes zoster (shingles)", "glycan_involvement": "gE is a glycoprotein required for viral entry and immune evasion.", "mechanism": "gE is essential for VZV infectivity and cell-to-cell spread, leading to shingles upon reactivation.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "high", "disease": "Herpes zoster ophthalmicus (HZO)", "glycan_involvement": "Glycosylation of gE is required for efficient viral spread in ocular tissues.", "mechanism": "gE mediates VZV infection of the ophthalmic branch of the trigeminal nerve, causing HZO.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "medium", "disease": "Acute retinal necrosis (ARN)", "glycan_involvement": "Glycosylation may facilitate immune evasion and tissue tropism.", "mechanism": "gE enables VZV to infect retinal cells, leading to necrosis.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "medium", "disease": "Anterior uveitis", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "VZV gE triggers immune-mediated inflammation in the anterior chamber.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "medium", "disease": "Keratitis", "glycan_involvement": "Glycosylation supports viral entry into corneal epithelium.", "mechanism": "gE mediates VZV infection of corneal cells, causing keratitis.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "medium", "disease": "Postherpetic neuralgia (PHN)", "glycan_involvement": "Glycosylation may affect neurotropism.", "mechanism": "gE-dependent VZV reactivation damages sensory neurons, leading to PHN.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "high", "disease": "Herpes zoster (shingles)", "glycan_involvement": "Recombinant gE is glycosylated to mimic native antigenicity.", "mechanism": "Shingrix vaccine uses recombinant gE to induce protective immunity against VZV reactivation.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "protective", "source_pmcid": "PMC12390273" }, { "confidence": "medium", "disease": "Herpes zoster ophthalmicus (HZO)", "glycan_involvement": "Glycosylation of vaccine antigen enhances immunogenicity.", "mechanism": "Shingrix-induced anti-gE immunity reduces HZO incidence.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "protective", "source_pmcid": "PMC12390273" }, { "confidence": "low", "disease": "Anterior uveitis", "glycan_involvement": "Glycosylated gE may trigger immune responses.", "mechanism": "Rare cases of anterior uveitis after VZV vaccination may be due to immune modulation by gE antigen.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "low", "disease": "Acute retinal necrosis (ARN)", "glycan_involvement": "Glycosylation status may influence viral reactivation.", "mechanism": "ARN after vaccination may result from reactivation of latent VZV or, rarely, vaccine strain infection involving gE.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12390273" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "N-glycosylation enhances viral growth and immune evasion.", "mechanism": "Gc mediates host cell attachment, membrane fusion, and immune evasion, enabling AKAV infection and disease.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Arthrogryposis-Hydranencephaly Syndrome (AHS)", "glycan_involvement": "N-glycosylation supports proper folding and function for tissue tropism.", "mechanism": "Gc facilitates viral entry into fetal tissues, leading to congenital malformations.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Abortion/stillbirth in ruminants", "glycan_involvement": "N-glycosylation modulates immune evasion and tissue invasion.", "mechanism": "Gc enables AKAV to infect placental and fetal tissues, causing reproductive failure.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Glycosylated epitopes improve antigenicity for serological assays.", "mechanism": "Gc-specific antibodies are used in ELISA, SNT, and immunochromatography for AKAV diagnosis.", "protein": "Gc protein (Akabane virus)", "relationship_type": "biomarker", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Glycosylation affects epitope presentation and immunogenicity.", "mechanism": "Gc neutralizing epitopes are core targets for subunit vaccine development.", "protein": "Gc protein (Akabane virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Glycosylation influences vaccine efficacy by modulating immune recognition.", "mechanism": "Vaccines targeting Gc induce neutralizing antibodies, conferring protection in animal models.", "protein": "Gc protein (Akabane virus)", "relationship_type": "protective", "source_pmcid": "PMC12390303" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Similar glycosylation patterns contribute to cross-reactivity.", "mechanism": "Gc shares antigenic cross-reactivity with SBV, enabling serological differentiation.", "protein": "Gc protein (Akabane virus)", "relationship_type": "biomarker", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Variable glycosylation sites modulate antigenicity and immune escape.", "mechanism": "Genetic variation in Gc N-terminal region drives immune evasion and host adaptation, influencing disease severity and transmission.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Gc glycosylation facilitates receptor binding.", "mechanism": "Gc interaction with host heparan sulfate proteoglycans is essential for viral attachment and entry.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "Akabane disease", "glycan_involvement": "Glycosylation supports proper folding and fusion activity.", "mechanism": "Gc fusion peptide mediates membrane fusion, critical for viral genome release and infection.", "protein": "Gc protein (Akabane virus)", "relationship_type": "causal", "source_pmcid": "PMC12390303" }, { "confidence": "high", "disease": "MHV68 latent infection", "glycan_involvement": "Glycosylation of gHgL is required for proper folding and immunogenicity.", "mechanism": "Target of neutralizing antibodies; mRNA vaccine encoding gHgL prevents latent infection.", "protein": "gH/gL complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390394" }, { "confidence": "high", "disease": "MHV68 latent infection", "glycan_involvement": "Glycosylation of gB is necessary for native conformation and T-cell epitope presentation.", "mechanism": "Induces protective CD8+ T-cell responses; mRNA vaccine encoding gB reduces latent infection.", "protein": "gB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390394" }, { "confidence": "medium", "disease": "Epstein\u2013Barr virus (EBV) infection", "glycan_involvement": "Glycosylation conserved and important for antigenicity.", "mechanism": "Homologous to EBV gH/gL; proposed as vaccine target to prevent EBV infection.", "protein": "gH/gL complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390394" }, { "confidence": "medium", "disease": "Epstein\u2013Barr virus (EBV) infection", "glycan_involvement": "Glycosylation required for proper folding and immune recognition.", "mechanism": "Homologous to EBV gB; proposed as vaccine target for cellular immunity.", "protein": "gB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390394" }, { "confidence": "medium", "disease": "Lymphoproliferative diseases", "glycan_involvement": "Glycosylation supports function and immune evasion.", "mechanism": "Mediates viral entry and establishment of latency, leading to lymphoproliferative disease.", "protein": "gH/gL complex", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "medium", "disease": "Lymphoproliferative diseases", "glycan_involvement": "Glycosylation supports protein function.", "mechanism": "Essential for viral entry and spread, contributing to disease.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "low", "disease": "Burkitt lymphoma", "glycan_involvement": "Glycosylation important for immune evasion and infectivity.", "mechanism": "EBV gH/gL mediates B cell infection and latency, a prerequisite for lymphoma development.", "protein": "gH/gL complex", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "EBV gB implicated in B cell infection, a risk factor for MS.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "low", "disease": "Infectious mononucleosis", "glycan_involvement": "Glycosylation required for function.", "mechanism": "EBV gH/gL mediates primary infection of epithelial and B cells.", "protein": "gH/gL complex", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "low", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation supports protein folding and immune evasion.", "mechanism": "EBV gB enables infection of epithelial cells, contributing to carcinogenesis.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12390394" }, { "confidence": "high", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "S1 is highly glycosylated, which affects receptor binding and immune recognition.", "mechanism": "S1 mediates host cell receptor binding and is essential for IBV infection and tissue tropism.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390407" }, { "confidence": "high", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation of S1 influences antigenicity and immunogenicity.", "mechanism": "S1 is the major target for neutralizing antibodies and vaccine design.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390407" }, { "confidence": "high", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "CHO cell-expressed S1 retains native glycosylation, enhancing immunogenicity.", "mechanism": "Vaccination with recombinant S1 (CHO-expressed, glycosylated) induces robust humoral and cellular immunity, conferring protection.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390407" }, { "confidence": "medium", "disease": "Renal injury in IBV infection", "glycan_involvement": "Glycosylated S1 elicits stronger IgG responses.", "mechanism": "High anti-S1 IgG levels correlate with reduced kidney pathology after IBV challenge.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390407" }, { "confidence": "high", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Native glycosylation preserved in CHO-expressed S1 enhances vaccine efficacy.", "mechanism": "S1-based nanoparticle vaccine (nAP205-S1) provides 100% protection against virulent IBV challenge.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390407" }, { "confidence": "medium", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation status affects antibody induction and protection.", "mechanism": "S1-specific IgG levels inversely correlate with kidney injury severity.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390407" }, { "confidence": "medium", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation may improve antigen presentation and T cell activation.", "mechanism": "S1 antigen displayed on AP205 nanoparticles enhances cellular (CD4+ T cell) immunity.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390407" }, { "confidence": "medium", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylated S1 improves assay sensitivity.", "mechanism": "S1-specific IgG ELISA used to monitor vaccine-induced immunity.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390407" }, { "confidence": "low", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "S2 is glycosylated, which may affect fusion efficiency.", "mechanism": "S2 mediates membrane fusion during IBV entry.", "protein": "Spike (S) glycoprotein S2 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390407" }, { "confidence": "medium", "disease": "Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation may affect cross-genotype antigenicity.", "mechanism": "Multivalent display of S1 from different genotypes on AP205 nanoparticles proposed for broad protection.", "protein": "Spike (S) glycoprotein S1 subunit", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390407" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and serum half-life.", "mechanism": "Albumin levels decrease in liver dysfunction due to impaired hepatic synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Glycosylation may affect renal filtration and loss.", "mechanism": "Albumin is lost in urine during nephrotic syndrome, leading to hypoalbuminemia.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "ALT is glycosylated; glycosylation may affect enzyme stability and secretion.", "mechanism": "ALT is released into serum during hepatocyte injury; elevated levels indicate liver damage.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "AST glycosylation may affect tissue distribution.", "mechanism": "AST is released during liver and muscle injury; elevated levels indicate tissue damage.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "ALP is heavily glycosylated; glycosylation affects activity and tissue specificity.", "mechanism": "ALP increases in cholestasis and bile duct injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Chronic hepatitis", "glycan_involvement": "Altered glycosylation may reflect disease state.", "mechanism": "Albumin decreases in chronic hepatitis due to reduced hepatic synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Improved glycosylation may enhance albumin stability.", "mechanism": "GB/MT supplementation increases albumin synthesis, supporting liver function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390411" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Potential modulation of glycosylation affecting ALT secretion.", "mechanism": "GB/MT supplementation reduces ALT, indicating hepatoprotective effect.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390411" }, { "confidence": "low", "disease": "Bleeding disorders", "glycan_involvement": "Glycosylation status may influence albumin's role in coagulation.", "mechanism": "GB may increase bleeding risk via platelet-activating factor inhibition; albumin levels may be affected in severe bleeding.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12390411" }, { "confidence": "low", "disease": "Seizure disorders", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "GB may be contraindicated in seizure-prone breeds; albumin not directly involved but may reflect overall health.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12390411" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation of RABV-G is essential for proper folding, antigenicity, and immunogenicity.", "mechanism": "RABV-G is the key antigen for vaccine-induced protective immunity; antibodies against RABV-G neutralize virus and prevent infection.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390428" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation maintains conformational epitopes required for neutralizing antibody recognition.", "mechanism": "Vaccination with glycosylated RABV-G elicits neutralizing antibodies that confer protection against lethal rabies challenge.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "protective", "source_pmcid": "PMC12390428" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects antigenicity and detection in immunoassays.", "mechanism": "RABV-G-specific IgG and neutralizing antibody titers are used as correlates of protective immunity in vaccine studies.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "biomarker", "source_pmcid": "PMC12390428" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation influences T cell epitope presentation and B cell recognition.", "mechanism": "RABV-G is targeted by both humoral (antibody) and cellular (T cell) immune responses induced by vaccines.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390428" }, { "confidence": "medium", "disease": "Encephalomyelitis", "glycan_involvement": "Glycosylation is required for proper folding and function of RABV-G in viral entry.", "mechanism": "RABV-G mediates viral entry into neurons, leading to CNS infection and fatal encephalomyelitis.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "causal", "source_pmcid": "PMC12390428" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "Overexpression leads to increased drug efflux and chemotherapy resistance.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390439" }, { "confidence": "high", "disease": "Canine mammary gland tumor", "glycan_involvement": "N-glycosylation essential for function.", "mechanism": "Upregulation mediates drug resistance via efflux of chemotherapeutics.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390439" }, { "confidence": "high", "disease": "Acute myeloid leukemia", "glycan_involvement": "N-glycosylation affects trafficking and stability.", "mechanism": "Overexpression correlates with resistance to anthracyclines and other drugs.", "protein": "MRP1 (ABCC1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390439" }, { "confidence": "medium", "disease": "Canine mammary gland tumor", "glycan_involvement": "N-glycosylation required for surface expression.", "mechanism": "Overexpression confers resistance to multiple chemotherapeutics.", "protein": "BCRP (ABCG2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390439" }, { "confidence": "medium", "disease": "Feline low-grade alimentary lymphoma", "glycan_involvement": "Glycosylation status may affect function; feline variants less efficient.", "mechanism": "Polymorphisms alter drug efflux and resistance profile.", "protein": "BCRP (ABCG2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390439" }, { "confidence": "medium", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation may influence stability and anti-apoptotic function.", "mechanism": "Overexpression linked to intrinsic chemotherapy resistance.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390439" }, { "confidence": "high", "disease": "Acute myeloid leukemia", "glycan_involvement": "Glycosylation may modulate anti-apoptotic activity.", "mechanism": "Overexpression inhibits apoptosis, conferring drug resistance.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390439" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Overexpression blocks death receptor-mediated apoptosis, leading to resistance.", "protein": "c-FLIP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390439" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation required for transporter activity.", "mechanism": "Reduced expression impairs drug influx, lowering intracellular drug levels.", "protein": "OATP1B1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390439" }, { "confidence": "high", "disease": "Canine lymphoma", "glycan_involvement": "N-glycosylation critical for function.", "mechanism": "Overexpression reduces intracellular doxorubicin/vincristine, causing resistance.", "protein": "ABCB1 (canine)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q28248" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390439" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Mediates viral entry by binding ACE2 and facilitating membrane fusion.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antibody accessibility and vaccine efficacy.", "mechanism": "Targeted by neutralizing antibodies and vaccines to block viral entry.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield modulates antigenicity and immune recognition.", "mechanism": "Mutations in S protein correlate with variant emergence and immune escape.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which influences S protein binding.", "mechanism": "Host receptor for S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Essential for viral polyprotein processing; inhibited by nirmatrelvir.", "protein": "Mpro (3CLpro, NSP5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Processes viral polyproteins and modulates host immune response.", "protein": "PLpro (NSP3)", "protein_enriched": { "function": "Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTD1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Catalyzes viral RNA synthesis; targeted by remdesivir and molnupiravir.", "protein": "RdRp (NSP12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390440" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "Glycosylation may affect persistence and immune modulation.", "mechanism": "Persistent S protein or immune response may contribute to post-acute sequelae.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390440" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation implicated in protein folding and virion assembly.", "mechanism": "Structural component essential for virion assembly and budding.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390440" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Furin is N-glycosylated; glycosylation affects its activity and S protein processing.", "mechanism": "Cleaves S protein at polybasic site, priming for membrane fusion.", "protein": "Furin", "relationship_type": "causal", "source_pmcid": "PMC12390440" }, { "confidence": "high", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "DOCK8 is a predicted glycoprotein; glycosylation may affect protein stability and immune synapse formation.", "mechanism": "Missense mutations in DOCK8 diminish NK cell cytolytic function, predisposing to CSS upon SARS-CoV-2 infection.", "protein": "DOCK8", "protein_enriched": { "function": "Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, v", "gene_name": "DOCK10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BY6" }, "relationship_type": "causal", "source_pmcid": "PMC12390453" }, { "confidence": "medium", "disease": "Multi-system Inflammatory Syndrome in Children (MIS-C)", "glycan_involvement": "Glycosylation may modulate DOCK8 function in immune cells.", "mechanism": "DOCK8 mutations act as partial dominant-negatives, disrupting lymphocyte cytolytic activity and contributing to MIS-C.", "protein": "DOCK8", "protein_enriched": { "function": "Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, v", "gene_name": "DOCK10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BY6" }, "relationship_type": "causal", "source_pmcid": "PMC12390453" }, { "confidence": "medium", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "Predicted glycosylation may affect DOCK2 localization/function.", "mechanism": "DOCK2 mutations impair actin cytoskeleton and cytolytic granule trafficking, predisposing to CSS.", "protein": "DOCK2", "protein_enriched": { "function": "Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF", "gene_name": "DOCK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92608" }, "relationship_type": "causal", "source_pmcid": "PMC12390453" }, { "confidence": "high", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation required for perforin stability and trafficking.", "mechanism": "Mutations in perforin gene impair cytolytic function, leading to HLH.", "protein": "Perforin (PRF1)", "relationship_type": "causal", "source_pmcid": "PMC12390453" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may affect protein-protein interactions in exocytosis.", "mechanism": "UNC13D mutations disrupt cytolytic granule exocytosis, causing HLH.", "protein": "UNC13D (Munc13-4)", "protein_enriched": { "function": "Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late e", "gene_name": "UNC13D", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q70J99" }, "relationship_type": "causal", "source_pmcid": "PMC12390453" }, { "confidence": "high", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "Heavily glycosylated; glycosylation critical for lysosomal targeting.", "mechanism": "CD107a surface expression marks NK cell degranulation; reduced in DOCK8/fHLH mutations.", "protein": "LAMP1 (CD107a)", "relationship_type": "biomarker", "source_pmcid": "PMC12390453" }, { "confidence": "medium", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "N-glycosylation affects fibrinogen function and clearance.", "mechanism": "Decreased fibrinogen (due to coagulopathy) lowers ESR, contributing to diagnostic ferritin/ESR ratio.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390453" }, { "confidence": "medium", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "Polysialylation modulates cell-cell interactions.", "mechanism": "CD56 is used to identify NK cells in functional assays; altered NK cell function in CSS.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12390453" }, { "confidence": "low", "disease": "Hyper-inflammatory states", "glycan_involvement": "Predicted glycosylation may affect immune signaling.", "mechanism": "DOCK11 deficiency newly associated with hyper-inflammation; role in CSS unknown.", "protein": "DOCK11", "protein_enriched": { "function": "Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP. Its interaction with presenilin proteins as well as its ability to st", "gene_name": "DOCK3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G06130KI", "G49108TO" ], "uniprot_id": "Q8IZD9" }, "relationship_type": "causal (proposed)", "source_pmcid": "PMC12390453" }, { "confidence": "high", "disease": "Severe COVID-19 Cytokine Storm Syndrome (CSS)", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "Elevated CRP is a marker of inflammation and CSS severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390453" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Gn is glycosylated; glycosylation is required for proper folding, virion incorporation, and immune evasion.", "mechanism": "Gn mediates receptor binding and virion anchoring, essential for viral entry and assembly.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Gc glycosylation affects tropism, entry efficiency, and antigenicity.", "mechanism": "Gc mediates membrane fusion between virus and host cell, enabling infection.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "GP38 is glycosylated and secreted; glycosylation facilitates folding and oligomerization.", "mechanism": "GP38 is essential for producing infectious particles and virion assembly.", "protein": "GP38", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation and proteolytic cleavage (furin, S1P) are essential for maturation and function.", "mechanism": "GPC is processed into mature envelope glycoproteins required for infectivity.", "protein": "GPC (glycoprotein precursor)", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Highly glycosylated; glycosylation increases sequence variability and immune escape.", "mechanism": "MLD contributes to immune evasion and cell tropism.", "protein": "MLD (mucin-like domain)", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Gn is a key antigen for vaccine development, eliciting neutralizing antibodies.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Gc is a key antigen for vaccine development, eliciting neutralizing antibodies.", "protein": "Gc", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390460" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation may influence immunogenicity and antigen presentation.", "mechanism": "GP38 is considered for vaccine design due to its role in virion assembly and immune evasion.", "protein": "GP38", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390460" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation is essential for secretion and membrane targeting.", "mechanism": "GP85 arises from glycosylation of MLD-GP38 and is involved in viral dissemination.", "protein": "GP85", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "low", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHF)", "glycan_involvement": "Glycosylation status not fully characterized; may affect adaptation and transmission.", "mechanism": "NSm contributes to virion assembly and virus\u2013host interactions, with positive selection in ticks.", "protein": "NSm", "relationship_type": "causal", "source_pmcid": "PMC12390460" }, { "confidence": "high", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Glycosylation of the G protein is essential for its proper folding, antigenicity, and function in viral infectivity.", "mechanism": "The G protein is the major surface antigen of IHNV, mediating viral entry and immune recognition.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12390467" }, { "confidence": "high", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Glycosylation of the G protein may affect vaccine efficacy by influencing antigen presentation and immune response.", "mechanism": "DNA vaccines encoding the G protein induce protective immunity against IHN in rainbow trout.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390467" }, { "confidence": "medium", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Glycan structures on the G protein modulate antibody binding and neutralization.", "mechanism": "Antibodies targeting the G protein confer protection against IHNV infection and disease.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "protective", "source_pmcid": "PMC12390467" }, { "confidence": "medium", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Glycosylation may affect detection sensitivity in immunoassays.", "mechanism": "Detection of G protein gene or protein is used for IHNV diagnosis and viral load quantification.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390467" }, { "confidence": "medium", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Glycosylation state of the G protein in vaccine preparations may influence immunogenicity.", "mechanism": "Inactivated and attenuated vaccines containing the G protein provide partial protection against IHN.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390467" }, { "confidence": "medium", "disease": "Infectious Hematopoietic Necrosis (IHN)", "glycan_involvement": "Amino acid changes may alter glycosylation sites, impacting antigenicity.", "mechanism": "Genetic variation in the G protein among IHNV genotypes affects vaccine efficacy and viral transmission.", "protein": "IHNV glycoprotein (G protein)", "protein_enriched": { "function": "Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of", "gene_name": "BMAL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8QGQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12390467" }, { "confidence": "high", "disease": "Herpes zoster", "glycan_involvement": "Glycosylation of gE is critical for its antigenicity and immune recognition.", "mechanism": "gE is the most abundant surface glycoprotein of VZV, essential for virus entry and cell-to-cell spread; targeted by recombinant zoster vaccine (RZV) to induce protective immune responses.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390494" }, { "confidence": "high", "disease": "Postherpetic neuropathy (PHN)", "glycan_involvement": "Glycosylation maintains gE structure and immunogenicity, enabling vaccine efficacy.", "mechanism": "Vaccination with gE-based RZV reduces HZ incidence, thereby preventing PHN as a complication.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390494" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gn is a glycoprotein; glycosylation is required for proper folding and function.", "mechanism": "Gn mediates receptor binding and is essential for SFTSV entry into host cells.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gc is a glycoprotein; glycosylation is required for function and immunogenicity.", "mechanism": "Gc contains the fusion peptide enabling viral-host membrane fusion and entry.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation of Gn/Gc affects antigenicity and immune recognition.", "mechanism": "Gn/Gc is the sole surface protein complex on SFTSV virions and is the main target for neutralizing antibodies and vaccine development.", "protein": "Gn/Gc complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation may influence epitope exposure and antibody binding.", "mechanism": "Antibodies against Gn inhibit viral entry and confer protection in animal models.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation may influence epitope exposure and antibody binding.", "mechanism": "Antibodies against Gc inhibit viral entry and confer protection in animal models.", "protein": "Gc", "relationship_type": "protective", "source_pmcid": "PMC12390526" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation status may affect assay sensitivity/specificity.", "mechanism": "Serological detection of anti-Gn/Gc antibodies indicates exposure or immune response to SFTSV.", "protein": "Gn/Gc complex", "relationship_type": "biomarker", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation is necessary for correct antigen conformation and immunogenicity.", "mechanism": "Vaccines encoding Gn/Gc induce protective humoral and cellular immunity.", "protein": "Gn/Gc complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390526" }, { "confidence": "medium", "disease": "Multiorgan dysfunction/failure (in SFTS context)", "glycan_involvement": "Glycosylation is required for efficient viral entry and pathogenesis.", "mechanism": "Viral entry via Gn/Gc leads to systemic infection and severe disease manifestations.", "protein": "Gn/Gc complex", "relationship_type": "causal", "source_pmcid": "PMC12390526" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation may affect antigenicity in diagnostic assays.", "mechanism": "Gn/Gc is used in ELISA assays to measure vaccine-induced antibody responses.", "protein": "Gn/Gc complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation is required for immunogenicity and vaccine efficacy.", "mechanism": "Prime-boost vaccination with Gn/Gc (mRNA or rVSV) protects mice from lethal SFTSV challenge.", "protein": "Gn/Gc complex", "relationship_type": "protective", "source_pmcid": "PMC12390526" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "HLA-I maturation and surface expression depend on proper glycosylation and ER chaperones.", "mechanism": "Downregulation of HLA-I on infected cells impairs CD8+ T cell recognition and viral clearance.", "protein": "HLA-I (Human Leukocyte Antigen Class I)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for HLA-II folding and trafficking.", "mechanism": "Suppression of IFN\u03b3-induced HLA-II expression impairs CD4+ T cell responses.", "protein": "HLA-II (Human Leukocyte Antigen Class II)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Indirect: Nsp1 reduces expression of glycoproteins and ER chaperones needed for glycoprotein maturation.", "mechanism": "Nsp1 blocks host translation, suppressing biosynthesis of HLA-I and HLA-II, leading to immune evasion.", "protein": "SARS-CoV-2 Nsp1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "medium", "disease": "Impaired antigen presentation", "glycan_involvement": "CALR is a lectin chaperone binding glycan moieties on nascent glycoproteins.", "mechanism": "Reduced CALR expression disrupts HLA-I folding and assembly.", "protein": "Calreticulin (CALR)", "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "medium", "disease": "Impaired antigen presentation", "glycan_involvement": "ERp57 acts in glycoprotein folding complexes.", "mechanism": "Downregulation impairs disulfide bond formation in HLA-I, affecting antigen presentation.", "protein": "ERp57 (PDIA3)", "protein_enriched": { "function": "Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568,", "gene_name": "PDIA3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P30101" }, "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "medium", "disease": "Impaired antigen presentation", "glycan_involvement": "CANX binds N-glycans on HLA-I for quality control.", "mechanism": "Reduced CANX expression impairs HLA-I maturation.", "protein": "Calnexin (CANX)", "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "medium", "disease": "Impaired antigen presentation", "glycan_involvement": "B2M is non-glycosylated but associates with glycosylated HLA-I heavy chain.", "mechanism": "Downregulation of B2M disrupts HLA-I complex formation and surface expression.", "protein": "\u03b22-microglobulin (B2M)", "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "ORF8 may induce ER stress affecting glycoprotein folding.", "mechanism": "High-level ORF8 overexpression can reduce HLA-I surface levels, possibly via ER stress.", "protein": "SARS-CoV-2 ORF8", "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD71 is highly glycosylated; its expression reflects ER/glycoprotein biosynthetic activity.", "mechanism": "CD71 surface levels are reduced in SARS-CoV-2-infected cells, indicating global suppression of glycoprotein expression.", "protein": "CD71 (Transferrin Receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12390542" }, { "confidence": "low", "disease": "Impaired antigen presentation", "glycan_involvement": "May interfere with glycoprotein trafficking and maturation.", "mechanism": "ORF3a can reduce HLA-I and HLA-II surface expression, possibly by affecting trafficking.", "protein": "SARS-CoV-2 ORF3a", "protein_enriched": { "function": "Plays a role in viral egress via lysosomal trafficking (PubMed:33157038, PubMed:33422265). Forms homotetrameric ion channels (viroporins) localized at endosomes and lysosomes, that may induce deacidif", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P0DTC3" }, "relationship_type": "causal", "source_pmcid": "PMC12390542" }, { "confidence": "high", "disease": "Simian Foamy Virus Infection", "glycan_involvement": "N-glycosylation sites in Env influence immune recognition and viral entry.", "mechanism": "Env mediates viral entry into host cells, enabling infection.", "protein": "Foamy Virus Envelope Glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC12390576" }, { "confidence": "high", "disease": "Zoonotic Foamy Virus Infection", "glycan_involvement": "Conformational epitopes near N8 glycosylation site are antibody targets.", "mechanism": "Neutralizing antibodies target SUvar region, blocking cell-free viral infectivity.", "protein": "Foamy Virus Surface Subunit (SU)", "relationship_type": "protective", "source_pmcid": "PMC12390576" }, { "confidence": "medium", "disease": "Zoonotic Foamy Virus Infection", "glycan_involvement": "Absence of glycan shielding at key epitopes prevents immune escape.", "mechanism": "Lack of glycan shielding in Env allows effective neutralizing antibody response, limiting transmission.", "protein": "Foamy Virus Envelope Glycoprotein (Env)", "relationship_type": "protective", "source_pmcid": "PMC12390576" }, { "confidence": "medium", "disease": "Simian Foamy Virus Infection", "glycan_involvement": "Glycosylation may stabilize GPC structure and function.", "mechanism": "GPC mediates membrane fusion and viral entry; structural similarity to other viral fusion proteins.", "protein": "Foamy Virus Glycoprotein Complex (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390576" }, { "confidence": "medium", "disease": "Simian Foamy Virus Infection", "glycan_involvement": "Glycosylation sites in RBD affect receptor binding and immune recognition.", "mechanism": "RBD interacts with heparan sulfate for cell entry; critical for infectivity.", "protein": "Gorilla Foamy Virus Env Receptor Binding Domain (RBD)", "relationship_type": "causal", "source_pmcid": "PMC12390576" }, { "confidence": "medium", "disease": "Zoonotic Foamy Virus Infection", "glycan_involvement": "Immunodominant region includes glycosylation sites affecting antibody binding.", "mechanism": "Env peptides (N96-V110) used in ELISA to detect infection in humans.", "protein": "Foamy Virus Envelope Glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC12390576" }, { "confidence": "low", "disease": "Arboviral Encephalitis", "glycan_involvement": "Not specified.", "mechanism": "Upregulated during arboviral infection in astrocytes; may modulate host gene expression.", "protein": "HERV4_4q22 (Human Endogenous Retrovirus protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12390576" }, { "confidence": "low", "disease": "Neurological Disorders", "glycan_involvement": "Not specified.", "mechanism": "HERV expression linked to neurogenesis and immune activation in neurological disease.", "protein": "HERV4_4q22 (Human Endogenous Retrovirus protein)", "relationship_type": "causal", "source_pmcid": "PMC12390576" }, { "confidence": "high", "disease": "Simian Foamy Virus Infection", "glycan_involvement": "Glycosylation sites shape epitope structure and antibody accessibility.", "mechanism": "Neutralizing antibodies against Env limit viremia and person-to-person transmission.", "protein": "Foamy Virus Envelope Glycoprotein (Env)", "relationship_type": "protective", "source_pmcid": "PMC12390576" }, { "confidence": "low", "disease": "HTLV-2 Infection", "glycan_involvement": "Not specified.", "mechanism": "Co-screening for SFV and HTLV-2 in epidemiological studies; familial clustering observed.", "protein": "Foamy Virus Envelope Glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC12390576" }, { "confidence": "high", "disease": "Antibiotic resistance", "glycan_involvement": "P-glycoprotein is a glycosylated membrane protein; glycosylation affects its stability and drug efflux function.", "mechanism": "Curcumin inhibits overexpression of P-glycoprotein, increasing intracellular drug accumulation and potentially reversing drug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390582" }, { "confidence": "medium", "disease": "Colibacillosis", "glycan_involvement": "No direct glycosylation mentioned; AI-2 signaling may interact with glycosylated host surfaces.", "mechanism": "LuxS is involved in AI-2 quorum sensing, promoting biofilm formation and virulence in E. coli.", "protein": "LuxS", "protein_enriched": { "function": "Catalyzes the alpha,beta-elimination reaction of D-cysteine and of several D-cysteine derivatives. It could be a defense mechanism against D-cysteine. Can also catalyze the degradation of 3-chloro-D-a", "gene_name": "dcyD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P76316" }, "relationship_type": "causal", "source_pmcid": "PMC12390582" }, { "confidence": "high", "disease": "Colibacillosis", "glycan_involvement": "Adhesins often recognize host glycan structures; glycosylation of adhesins and/or host receptors is critical for binding.", "mechanism": "APEC adhesins mediate bacterial attachment to host epithelial cells, facilitating infection.", "protein": "Adhesins (APEC)", "relationship_type": "causal", "source_pmcid": "PMC12390582" }, { "confidence": "medium", "disease": "Colibacillosis", "glycan_involvement": "Many acute-phase proteins are glycosylated; glycosylation modulates their function and clearance.", "mechanism": "Acute-phase proteins increase during E. coli infection, indicating inflammation.", "protein": "Acute-phase proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12390582" }, { "confidence": "high", "disease": "Pulmonary inflammation", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "IL-6 is upregulated during acute lung inflammation in response to E. coli infection.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390582" }, { "confidence": "high", "disease": "Pulmonary inflammation", "glycan_involvement": "TNF is a glycoprotein; glycosylation modulates its activity.", "mechanism": "TNF is released during acute inflammatory response to E. coli infection.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "biomarker", "source_pmcid": "PMC12390582" }, { "confidence": "medium", "disease": "Colibacillosis", "glycan_involvement": "Many PRRs are glycoproteins; glycosylation is important for ligand recognition and signaling.", "mechanism": "PRRs recognize bacterial PAMPs, triggering immune response.", "protein": "Pattern Recognition Receptors (PRRs)", "relationship_type": "causal", "source_pmcid": "PMC12390582" }, { "confidence": "low", "disease": "Pulmonary inflammation", "glycan_involvement": "Glycosylation status not specified; possible impact on stability.", "mechanism": "Curcumin upregulates SOD1, reducing oxidative stress in lung tissue.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "protective", "source_pmcid": "PMC12390582" }, { "confidence": "low", "disease": "Pulmonary inflammation", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "Curcumin upregulates GPX1, enhancing antioxidant defense in lungs.", "protein": "Glutathione peroxidase 1 (GPX1)", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide (PubMed:10691967).", "gene_name": "CAT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00432" }, "relationship_type": "protective", "source_pmcid": "PMC12390582" }, { "confidence": "low", "disease": "Pulmonary inflammation", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "Curcumin upregulates CAT, reducing ROS-mediated tissue damage.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC12390582" }, { "confidence": "high", "disease": "H9N2 Avian Influenza", "glycan_involvement": "HA is heavily glycosylated; glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral attachment to host cell sialic acid receptors, enabling infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "H9N2 Avian Influenza", "glycan_involvement": "Glycosylation sites on HA affect antigenicity and antibody recognition.", "mechanism": "Vaccine-induced antibodies block HA-sialic acid interaction, preventing viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "H9N2 Avian Influenza", "glycan_involvement": "NA glycosylation influences enzymatic activity and immune recognition.", "mechanism": "NA enables viral release from host cells; antibodies against NA reduce viral spread.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390594" }, { "confidence": "medium", "disease": "H9N2 Avian Influenza", "glycan_involvement": "M2e is not glycosylated; its exposure is influenced by HA/NA glycosylation.", "mechanism": "M2e is conserved; antibodies against M2e provide cross-strain protection.", "protein": "Matrix protein 2 extracellular domain (M2e)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390594" }, { "confidence": "medium", "disease": "Co-infection (SG + H9N2)", "glycan_involvement": "Glycosylation affects HA immunogenicity and cross-reactivity.", "mechanism": "HA antibody titers correlate with protection and disease severity in co-infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "Fowl Typhoid (FT)", "glycan_involvement": "LPS glycan structure determines endotoxicity and immune activation.", "mechanism": "LPS is a major virulence factor, triggering host immune response and septicemia.", "protein": "Salmonella Gallinarum LPS", "relationship_type": "causal", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "Fowl Typhoid (FT)", "glycan_involvement": "pagL deletion alters LPS acylation, reducing TLR4-mediated inflammation.", "mechanism": "Attenuated SG with modified LPS reduces endotoxicity and enhances vaccine safety.", "protein": "Salmonella Gallinarum LPS", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390594" }, { "confidence": "low", "disease": "Fowl Typhoid (FT)", "glycan_involvement": "HA glycosylation may affect immune modulation in co-infection.", "mechanism": "HA expression in SG vector induces immune responses that may modulate FT severity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390594" }, { "confidence": "medium", "disease": "Co-infection (SG + H9N2)", "glycan_involvement": "NA glycosylation impacts immune recognition and vaccine efficacy.", "mechanism": "NA-M2e fusion in vaccine enhances cross-protection in co-infected birds.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "H9N2 Avian Influenza", "glycan_involvement": "Glycosylation modulates HA antigenicity and HI assay sensitivity.", "mechanism": "HI titer against HA is a correlate of protection in vaccinated birds.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390594" }, { "confidence": "high", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "N-glycosylation affects fibrinogen stability and function.", "mechanism": "Low fibrinogen (hypofibrinogenemia) is associated with increased mortality in HLH secondary to dengue.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "high", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is glycosylated, which may affect its serum stability.", "mechanism": "Hyperferritinemia is a diagnostic and prognostic marker for HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates receptor shedding and detection.", "mechanism": "Elevated sIL-2R is a diagnostic criterion for HLH.", "protein": "Soluble Interleukin-2 Receptor (sIL-2R/CD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG is used as immunomodulatory therapy in HLH.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390640" }, { "confidence": "high", "disease": "Dengue Virus Infection", "glycan_involvement": "N-glycosylation is essential for infectivity and immune evasion.", "mechanism": "Viral E glycoprotein mediates host cell entry and immune response.", "protein": "Dengue Virus Envelope Protein (E)", "relationship_type": "causal", "source_pmcid": "PMC12390640" }, { "confidence": "low", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "N-glycosylation affects serum half-life and receptor binding.", "mechanism": "Altered iron metabolism in HLH may involve transferrin.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates receptor function and antibody binding.", "mechanism": "Low or absent NK cell activity is a diagnostic criterion for HLH.", "protein": "Natural Killer Cell Receptor (CD16/Fc\u03b3RIII)", "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Minimal; not a major glycoprotein.", "mechanism": "Elevated ALT indicates liver injury, associated with poor prognosis in HLH.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Minimal; not a major glycoprotein.", "mechanism": "Elevated AST is associated with hepatic dysfunction and mortality in HLH.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390640" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "Dengue E glycoprotein triggers immune activation leading to HLH.", "protein": "Dengue Virus Envelope Protein (E)", "relationship_type": "causal", "source_pmcid": "PMC12390640" }, { "confidence": "high", "disease": "Gammaherpesvirus infection (GPXV)", "glycan_involvement": "Glycosylation of gB is critical for proper folding and function in viral entry", "mechanism": "Mediates viral entry into host cells, essential for infection", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390642" }, { "confidence": "medium", "disease": "Latency-associated disease", "glycan_involvement": "Glycosylation may affect tropism and immune recognition", "mechanism": "Facilitates initial infection, enabling establishment of latency", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390642" }, { "confidence": "medium", "disease": "Latency-associated disease", "glycan_involvement": "Potential O-glycosylation may regulate nuclear localization and stability", "mechanism": "Tethers viral episomes to host chromatin, maintaining latency", "protein": "Latency-Associated Nuclear Antigen (LANA, ORF73)", "relationship_type": "causal", "source_pmcid": "PMC12390642" }, { "confidence": "medium", "disease": "Immune evasion-related disease", "glycan_involvement": "Glycosylation may be required for secretion and immunomodulatory activity", "mechanism": "Mimics host IL-10 to suppress immune response, promoting viral persistence", "protein": "Viral Interleukin-10 homolog (vIL-10)", "relationship_type": "causal", "source_pmcid": "PMC12390642" }, { "confidence": "medium", "disease": "Immune evasion-related disease", "glycan_involvement": "Glycan shielding may affect antibody accessibility", "mechanism": "Target for neutralizing antibodies and vaccine development", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390642" }, { "confidence": "low", "disease": "Gammaherpesvirus infection (GPXV)", "glycan_involvement": "Possible glycosylation may affect detection", "mechanism": "Expression indicates latent infection", "protein": "Latency-Associated Nuclear Antigen (LANA, ORF73)", "relationship_type": "biomarker", "source_pmcid": "PMC12390642" }, { "confidence": "high", "disease": "Yezo virus infection", "glycan_involvement": "Glycosylation of GPC is essential for proper folding, trafficking, and function of viral envelope proteins.", "mechanism": "GPC is cleaved into mature Gn and Gc glycoproteins that mediate host cell receptor recognition and viral entry.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "high", "disease": "Yezo virus infection", "glycan_involvement": "Gn is glycosylated, which is critical for receptor binding and immune evasion.", "mechanism": "Gn mediates attachment to host cell receptors, facilitating viral entry.", "protein": "Yezo virus Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "high", "disease": "Yezo virus infection", "glycan_involvement": "Gc glycosylation affects fusion activity and antigenicity.", "mechanism": "Gc mediates membrane fusion during viral entry.", "protein": "Yezo virus Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Acute febrile illness", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "GPC-derived glycoproteins enable viral infection leading to febrile symptoms.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Severe neurological disorder", "glycan_involvement": "Glycosylation may influence neurotropism and immune evasion.", "mechanism": "GPC enables neuroinvasion by facilitating viral entry into neural cells.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "high", "disease": "Yezo virus infection", "glycan_involvement": "No direct glycosylation reported for N; function is primarily RNA binding.", "mechanism": "N binds viral RNA, forming ribonucleoprotein complexes essential for replication; structural features may be targeted by antivirals.", "protein": "Yezo virus nucleoprotein (N)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Yezo virus infection", "glycan_involvement": "No direct glycosylation; domain is protease-like.", "mechanism": "OTU-like domain modulates host innate immunity and may influence disease severity.", "protein": "Yezo virus OTU-like domain (L protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Leukopenia", "glycan_involvement": "Glycosylation may affect immune cell targeting.", "mechanism": "GPC-mediated infection leads to immune cell depletion.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may modulate pathogenicity.", "mechanism": "GPC enables viral infection of cells involved in platelet production.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC12390643" }, { "confidence": "medium", "disease": "Crimean\u2013Congo hemorrhagic fever (CCHFV)", "glycan_involvement": "Glycosylation patterns may be conserved and relevant for cross-reactivity.", "mechanism": "YEZV GPC shares structural similarity with CCHFV GPC, suggesting similar pathogenic mechanisms.", "protein": "Yezo virus glycoprotein precursor (GPC)", "relationship_type": "structural_homology", "source_pmcid": "PMC12390643" }, { "confidence": "high", "disease": "Western equine encephalitis", "glycan_involvement": "E2 is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "E2 mediates viral attachment to host cells, essential for infection and pathogenesis.", "protein": "E2 glycoprotein (WEEV)", "relationship_type": "causal", "source_pmcid": "PMC12390645" }, { "confidence": "high", "disease": "Western equine encephalitis", "glycan_involvement": "E1 is a glycoprotein; glycosylation may influence fusion efficiency and immune response.", "mechanism": "E1 mediates membrane fusion during viral entry, required for infection.", "protein": "E1 glycoprotein (WEEV)", "relationship_type": "causal", "source_pmcid": "PMC12390645" }, { "confidence": "high", "disease": "Western equine encephalitis", "glycan_involvement": "Glycosylation may affect epitope presentation and antibody binding.", "mechanism": "E2 is the main target of neutralizing antibodies; used in serological diagnostics (PRNT).", "protein": "E2 glycoprotein (WEEV)", "relationship_type": "biomarker", "source_pmcid": "PMC12390645" }, { "confidence": "medium", "disease": "Western equine encephalitis", "glycan_involvement": "Glycosylation may modulate epitope accessibility.", "mechanism": "E1 contains conserved epitopes recognized by neutralizing antibodies; used in diagnostics.", "protein": "E1 glycoprotein (WEEV)", "relationship_type": "biomarker", "source_pmcid": "PMC12390645" }, { "confidence": "medium", "disease": "Western equine encephalitis", "glycan_involvement": "Glycosylation status may influence vaccine efficacy and immunogenicity.", "mechanism": "E2 is a target for vaccine development and neutralizing antibody therapies.", "protein": "E2 glycoprotein (WEEV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390645" }, { "confidence": "medium", "disease": "Western equine encephalitis", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "E1 is a target for broadly neutralizing antibodies and vaccine design.", "protein": "E1 glycoprotein (WEEV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390645" }, { "confidence": "high", "disease": "Western equine encephalitis virus infection", "glycan_involvement": "Glycosylation may modulate neutralization sensitivity.", "mechanism": "Antibodies against E2 confer protection by neutralizing virus.", "protein": "E2 glycoprotein (WEEV)", "relationship_type": "protective", "source_pmcid": "PMC12390645" }, { "confidence": "medium", "disease": "Western equine encephalitis virus infection", "glycan_involvement": "Glycosylation may affect breadth of antibody response.", "mechanism": "Antibodies against E1 can neutralize virus and provide protection.", "protein": "E1 glycoprotein (WEEV)", "relationship_type": "protective", "source_pmcid": "PMC12390645" }, { "confidence": "high", "disease": "Western equine encephalitis", "glycan_involvement": "Glycosylation not directly relevant to WEEV diagnostics.", "mechanism": "VSV G is not recognized by anti-WEEV antibodies; used to confirm assay specificity.", "protein": "VSV G glycoprotein", "relationship_type": "biomarker (negative control)", "source_pmcid": "PMC12390645" }, { "confidence": "low", "disease": "Western equine encephalitis", "glycan_involvement": "Potential glycosylation may influence virion structure.", "mechanism": "E3 is part of the envelope polyprotein; may contribute to virion assembly and immunogenicity.", "protein": "E3 glycoprotein (WEEV)", "relationship_type": "structural/biomarker", "source_pmcid": "PMC12390645" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation required for proper folding and receptor binding", "mechanism": "Mediates viral entry into host cells via ephrin-B2/B3 receptors", "protein": "Nipah virus attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390646" }, { "confidence": "high", "disease": "Hendra virus infection", "glycan_involvement": "Glycosylation required for antigenicity and function", "mechanism": "Mediates viral entry into host cells via ephrin-B2/B3 receptors", "protein": "Hendra virus attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390646" }, { "confidence": "high", "disease": "Cedar virus infection", "glycan_involvement": "Glycosylation supports antigenicity and receptor interaction", "mechanism": "Mediates viral entry into host cells via ephrin-B1/B2; lacks virulence factors", "protein": "Cedar virus attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390646" }, { "confidence": "medium", "disease": "Ghana virus infection", "glycan_involvement": "Glycosylation likely required for antigenicity and function", "mechanism": "Presumed to mediate viral entry via ephrin-B2; human exposure detected serologically", "protein": "Ghana virus attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390646" }, { "confidence": "high", "disease": "Menangle virus infection", "glycan_involvement": "Glycosylation required for hemagglutinin-neuraminidase activity", "mechanism": "Mediates viral attachment and fusion; causes febrile illness and rash in humans", "protein": "Menangle virus hemagglutinin-neuraminidase (HN)", "relationship_type": "causal", "source_pmcid": "PMC12390646" }, { "confidence": "medium", "disease": "Acute febrile illness", "glycan_involvement": "Glycosylation preserves antigenic epitopes for antibody detection", "mechanism": "Serologic detection of anti-CedV G antibodies in humans with febrile illness indicates exposure", "protein": "Cedar virus attachment glycoprotein (G)", "relationship_type": "biomarker", "source_pmcid": "PMC12390646" }, { "confidence": "medium", "disease": "Acute febrile illness", "glycan_involvement": "Glycosylation preserves antigenic epitopes for antibody detection", "mechanism": "Serologic detection of anti-GhV G antibodies in humans with febrile illness indicates exposure", "protein": "Ghana virus attachment glycoprotein (G)", "relationship_type": "biomarker", "source_pmcid": "PMC12390646" }, { "confidence": "medium", "disease": "Acute febrile illness", "glycan_involvement": "Glycosylation preserves antigenic epitopes for antibody detection", "mechanism": "Serologic detection of anti-MenV HN antibodies in humans with febrile illness indicates exposure", "protein": "Menangle virus hemagglutinin-neuraminidase (HN)", "relationship_type": "biomarker", "source_pmcid": "PMC12390646" }, { "confidence": "medium", "disease": "Cedar virus infection", "glycan_involvement": "Glycosylation maintains neutralizing epitopes", "mechanism": "Neutralizing antibodies detected in human serum; infection is non-pathogenic", "protein": "Cedar virus attachment glycoprotein (G)", "relationship_type": "protective", "source_pmcid": "PMC12390646" }, { "confidence": "high", "disease": "Acute febrile illness", "glycan_involvement": "Glycosylation required for antigenicity; absence of antibodies suggests no exposure", "mechanism": "No serologic evidence of anti-NiV G antibodies in Cambodian febrile illness cohort", "protein": "Nipah virus attachment glycoprotein (G)", "relationship_type": "biomarker", "source_pmcid": "PMC12390646" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Glycosylation by host enzymes is required for function.", "mechanism": "Modulates inflammatory myeloid cells, promoting immune evasion and dissemination.", "protein": "Serp-1", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "inflammatory diseases", "glycan_involvement": "Glycosylation critical for anti-inflammatory activity.", "mechanism": "Purified Serp-1 acts as anti-inflammatory drug in viral and non-viral inflammatory diseases.", "protein": "Serp-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Directly modifies glycan structures on proteins.", "mechanism": "Catalyzes sialylation of host and viral glycoproteins, affecting immune evasion and virulence.", "protein": "M138 (sialyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "medium", "disease": "myxomatosis", "glycan_involvement": "Secreted glycoprotein; glycosylation likely affects stability and function.", "mechanism": "Binds chemokines (RANTES, IL-8), modulating immune cell recruitment and reducing detection.", "protein": "M-T1 (M001R/L)", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect TNF binding.", "mechanism": "Binds rabbit TNF, inhibiting apoptosis and immune response.", "protein": "M-T2 (M002R/L)", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Downregulates CD4 and MHC-I via lysosomal degradation, dampening acquired immunity.", "protein": "M153", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "medium", "disease": "myxomatosis", "glycan_involvement": "Surface glycoprotein; glycosylation may affect immune cell interactions.", "mechanism": "Modulates monocyte/macrophage activation and migration, promoting pathogenesis.", "protein": "M141", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "medium", "disease": "myxomatosis", "glycan_involvement": "Membrane glycoprotein; glycosylation may affect cell signaling.", "mechanism": "Modulates monocyte/macrophage activation/recruitment to lesions.", "protein": "M128", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Secreted glycoprotein; glycosylation likely affects chemokine binding.", "mechanism": "Binds IFN\u03b3 and chemokines, regulating leukocyte localization and immune response.", "protein": "M-T7 (M007R/L)", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "myxomatosis", "glycan_involvement": "Intracellular glycoprotein; glycosylation may affect stability.", "mechanism": "Prevents activation of host PKR, avoiding translational shutdown.", "protein": "M029", "relationship_type": "causal", "source_pmcid": "PMC12390650" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation affects antigenicity and immune evasion.", "mechanism": "VP7 is a major antigenic glycoprotein forming the outer capsid, mediating host immune recognition and viral entry.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "causal", "source_pmcid": "PMC12390652" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation modulates host cell binding and immune escape.", "mechanism": "VP4 spike glycoprotein mediates host cell attachment and penetration.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390652" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation may affect toxin activity and secretion.", "mechanism": "NSP4 acts as a viral enterotoxin, disrupting calcium homeostasis and contributing to diarrhea.", "protein": "NSP4", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11194" }, "relationship_type": "causal", "source_pmcid": "PMC12390652" }, { "confidence": "medium", "disease": "Neonatal diarrhea", "glycan_involvement": "Glycosylation influences host range and age-specific tropism.", "mechanism": "Certain VP4 (P[6]) lineages are associated with increased infection rates in neonates.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390652" }, { "confidence": "low", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Potential impact on protein folding and function.", "mechanism": "Rare E6 genotype linked to emergent and reassortant strains, possibly altering virulence.", "protein": "NSP4 (E6 genotype)", "relationship_type": "causal", "source_pmcid": "PMC12390652" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation site variation may affect immune recognition.", "mechanism": "VP7 lineage shifts reflect viral evolution and epidemiological trends.", "protein": "VP7 (Lineage IVa/V variants)", "relationship_type": "biomarker", "source_pmcid": "PMC12390652" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation may influence lineage-specific host interactions.", "mechanism": "P[6]-Ia lineage associated with specific geographic and epidemiological patterns.", "protein": "VP4 (P[6]-Ia lineage)", "relationship_type": "biomarker", "source_pmcid": "PMC12390652" }, { "confidence": "low", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Possible effect on protein stability and function.", "mechanism": "E2 genotype associated with emergent DS-1-like strains.", "protein": "NSP4 (E2 genotype)", "relationship_type": "biomarker", "source_pmcid": "PMC12390652" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation impacts epitope accessibility.", "mechanism": "Target for neutralizing antibodies and vaccine design.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390652" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation affects antigenic structure.", "mechanism": "Target for neutralizing antibodies and vaccine design.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390652" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation of S protein is essential for proper folding, receptor interaction, and immune evasion.", "mechanism": "Mediates host cell entry via receptor binding and membrane fusion, initiating infection.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation in S1 modulates receptor binding and antigenic variation.", "mechanism": "S1 subunit binds host cell receptors, determines tissue tropism and antigenicity.", "protein": "S1 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "medium", "disease": "Nephritis (IBV-associated)", "glycan_involvement": "Glycosylation affects tissue tropism and immune escape.", "mechanism": "Certain IBV strains with S protein variants infect renal tissue, causing nephritis.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "medium", "disease": "Egg production drop", "glycan_involvement": "Glycosylation influences viral spread to reproductive organs.", "mechanism": "IBV S protein variants infect oviduct, impairing reproductive function.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation sites contribute to antigenic diversity.", "mechanism": "S1 sequence variation is used for lineage/genotype classification and outbreak tracking.", "protein": "S1 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation can mask epitopes, affecting vaccine efficacy.", "mechanism": "Targeted by neutralizing antibodies induced by vaccines.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation status affects immunogenicity and cross-protection.", "mechanism": "Vaccines based on S1 elicit protective immunity.", "protein": "S1 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Altered glycosylation patterns may result from recombination, impacting antigenicity.", "mechanism": "Recombination in S gene leads to emergence of new IBV variants causing outbreaks.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation in hypervariable regions modulates immune recognition.", "mechanism": "Positive selection in S1 receptor-binding domain drives immune escape and variant emergence.", "protein": "S1 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Infectious bronchitis", "glycan_involvement": "Glycosylation changes may accompany recombination, affecting virulence and immune evasion.", "mechanism": "Vaccine-driven recombination in S gene leads to vaccine-derived pathogenic strains.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390653" }, { "confidence": "high", "disease": "Human metapneumovirus infection", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "F protein mediates viral entry; targeted by neutralizing antibodies, vaccines, and fusion inhibitors.", "protein": "Fusion (F) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Human metapneumovirus infection", "glycan_involvement": "Heavily glycosylated; glycosylation shields from immune detection.", "mechanism": "G protein mediates viral attachment and modulates host immune response.", "protein": "Attachment (G) protein", "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation influences tissue tropism and immune evasion.", "mechanism": "F protein enables HMPV to infect lower respiratory tract, causing bronchiolitis.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation modulates fusion activity and immune response.", "mechanism": "F protein is essential for viral fusion and spread in lung tissue.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Human metapneumovirus infection", "glycan_involvement": "Glycan shielding affects epitope accessibility.", "mechanism": "Prefusion conformation exposes neutralizing epitopes targeted by potent mAbs and vaccines.", "protein": "Prefusion F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390667" }, { "confidence": "medium", "disease": "Human metapneumovirus infection", "glycan_involvement": "Glycosylation patterns differ from preF, affecting immunogenicity.", "mechanism": "Postfusion F is less immunogenic but still targeted by some neutralizing antibodies.", "protein": "Postfusion F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Human metapneumovirus infection", "glycan_involvement": "Sulfated glycan structure is essential for viral binding.", "mechanism": "Acts as host cell receptor for HMPV attachment via F and G proteins.", "protein": "Heparan sulfate", "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "medium", "disease": "Human metapneumovirus infection", "glycan_involvement": "Mimics host glycosaminoglycans to block glycoprotein-mediated entry.", "mechanism": "Heparin and derivatives inhibit viral attachment by competing with heparan sulfate.", "protein": "Heparin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390667" }, { "confidence": "medium", "disease": "Human metapneumovirus infection", "glycan_involvement": "Glycosylation may affect immune modulation.", "mechanism": "SH protein modulates host immune response and contributes to immune evasion.", "protein": "SH protein", "protein_enriched": { "function": "Ribonucleocapsid-associated protein that interacts with the phosphoprotein (P), thereby increasing replication accuracy and processivity of the polymerase complex", "gene_name": "P/V/C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03424" }, "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "medium", "disease": "Vaccine-associated enhanced disease (VAED)", "glycan_involvement": "Glycosylation may contribute to immune dysregulation.", "mechanism": "G protein and aberrant immune responses to it implicated in VAED after inactivated vaccines.", "protein": "G protein", "relationship_type": "causal", "source_pmcid": "PMC12390667" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Binds \u03b2-galactoside glycans; glycosylation modulates its function.", "mechanism": "Galectin-3 mediates inflammation and fibrosis, elevated in chronic heart failure.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "medium", "disease": "Fibrotic heart lesions", "glycan_involvement": "Lectin activity depends on glycan recognition.", "mechanism": "Galectin-3 is upregulated in fibrotic processes and chronic inflammation.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "low", "disease": "White muscle disease (WMD)", "glycan_involvement": "Glycan binding required for function; not altered in acute WMD.", "mechanism": "No significant elevation in acute/subacute WMD; may be relevant in chronic/fibrotic stages.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "NT-proBNP is glycosylated, which affects its stability and detection.", "mechanism": "Released from cardiac myocytes in response to wall stress; elevated in heart failure.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "low", "disease": "White muscle disease (WMD)", "glycan_involvement": "Glycosylation status not altered in WMD.", "mechanism": "Not significantly elevated in WMD; may not reflect myocardial injury due to necrosis.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "high", "disease": "White muscle disease (WMD)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Elevated in serum due to cardiac myocyte injury/necrosis in WMD.", "protein": "Cardiac troponin I (cTnI)", "protein_enriched": { "function": "With S4 and S5 plays an important role in translational accuracy. Located at the interface of the 30S and 50S subunits (By similarity)", "gene_name": "rps12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19461" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "medium", "disease": "White muscle disease (WMD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated due to muscle cell injury; reflects both cardiac and skeletal muscle damage.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "low", "disease": "Skeletal muscle necrosis", "glycan_involvement": "Glycan binding required for function.", "mechanism": "No significant elevation in acute muscle necrosis; may be relevant in chronic/fibrotic muscle disease.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "medium", "disease": "Myocardial injury", "glycan_involvement": "Glycosylation affects detection; not altered in WMD.", "mechanism": "Typically elevated in myocardial strain, but not in necrosis-dominated WMD.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "high", "disease": "Heart failure (other species)", "glycan_involvement": "Lectin activity depends on glycan recognition.", "mechanism": "Elevated in chronic heart failure in cats/dogs; not in acute muscle necrosis.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12390671" }, { "confidence": "high", "disease": "Subclinical BuHV-1 infection", "glycan_involvement": "Envelope glycosylation may affect immune recognition", "mechanism": "gC sequence variation distinguishes BuHV-1 clades associated with subclinical infection", "protein": "Glycoprotein C (gC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390673" }, { "confidence": "high", "disease": "Clinical BuHV-1 disease (vulvovaginitis, pustular lesions, abortion)", "glycan_involvement": "Glycosylation may modulate tropism and virulence", "mechanism": "gD sequence divergence in BuHV-1i strains correlates with clinical disease manifestations", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "causal", "source_pmcid": "PMC12390673" }, { "confidence": "high", "disease": "Diagnostic confusion (false positives)", "glycan_involvement": "Glycosylation impacts antigenicity and diagnostic specificity", "mechanism": "gE antigenic similarity between BuHV-1 and BoHV-1/5 causes cross-reactivity in serological assays", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390673" }, { "confidence": "high", "disease": "Vaccine escape/inefficacy", "glycan_involvement": "Glycosylation may alter epitope accessibility", "mechanism": "Antigenic divergence in gD of BuHV-1i strains reduces efficacy of BoHV-1 gE-deleted vaccines", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390673" }, { "confidence": "medium", "disease": "Cross-species transmission (cattle, goats)", "glycan_involvement": "Glycosylation may influence host cell binding", "mechanism": "gC variation facilitates host adaptation and interspecies jumps", "protein": "Glycoprotein C (gC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390673" }, { "confidence": "medium", "disease": "Respiratory disease (mild signs)", "glycan_involvement": "Glycosylation may affect tissue tropism", "mechanism": "gD recombination with BoHV-1 in BuHV-1i strain 20287N linked to respiratory tropism", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "causal", "source_pmcid": "PMC12390673" }, { "confidence": "medium", "disease": "Vaccine escape/inefficacy", "glycan_involvement": "Glycosylation impacts immunogenicity", "mechanism": "gE antigenic diversity in BuHV-1i strains reduces vaccine coverage", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390673" }, { "confidence": "high", "disease": "Diagnostic confusion (false positives)", "glycan_involvement": "Glycosylation affects antigenic profile", "mechanism": "gD antigenic overlap between BuHV-1 and BoHV-1/5 complicates serological differentiation", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390673" }, { "confidence": "medium", "disease": "Clinical BuHV-1 disease (vulvovaginitis, abortion)", "glycan_involvement": "Glycosylation may modulate immune evasion", "mechanism": "gC subclade divergence in BuHV-1i strains associated with clinical disease", "protein": "Glycoprotein C (gC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390673" }, { "confidence": "medium", "disease": "Cross-species transmission (cattle, goats)", "glycan_involvement": "Glycosylation may influence host range", "mechanism": "gE antigenic variation facilitates infection of non-buffalo hosts", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "causal", "source_pmcid": "PMC12390673" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "APP is a type I membrane glycoprotein; glycosylation may affect processing and secretion.", "mechanism": "APP is cleaved to produce A\u03b2, which accumulates in drusen and promotes AMD pathology.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation state may influence aggregation.", "mechanism": "A\u03b2 accumulates in drusen, induces inflammation and oxidative stress, contributing to AMD progression.", "protein": "Amyloid beta peptide (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Derived from glycosylated APP; glycosylation may modulate toxicity.", "mechanism": "A\u03b2 aggregates form senile plaques, driving neurodegeneration.", "protein": "Amyloid beta peptide (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Herpetic retinitis", "glycan_involvement": "Viral glycoproteins interact with host glycoprotein receptors for entry.", "mechanism": "gE/gI mediate HSV-1 neuronal transport and retinal infection.", "protein": "Herpes simplex virus glycoprotein E (gE)/glycoprotein I (gI)", "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Herpetic retinitis", "glycan_involvement": "Glycosaminoglycan chains are essential for viral binding.", "mechanism": "Serve as HSV-1 entry receptors on RPE and neuronal cells.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "medium", "disease": "Herpetic retinitis", "glycan_involvement": "Nectin-1 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "HSV-1 uses nectin-1 for entry into RPE cells.", "protein": "Nectin-1", "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "CD46 is a membrane glycoprotein; glycosylation may affect complement regulation.", "mechanism": "Downregulation by viral infection leads to complement hyperactivation and RPE damage.", "protein": "CD46", "protein_enriched": { "function": "Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in th", "gene_name": "CD46", "glycan_count": 60, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G61846BY", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G34989PA", "G40834TG", "G41071NU", "G43223CG", "G45395BF", "G48414YA", "G59324HL", "G60033FS", "G60177UT", "G62765YT", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G94470IW", "G98611JV", "G57321FI", "G03644CB", "G04854VP", "G07810QS", "G08290VR", "G12341GU", "G13131HA", "G15169WU", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G41247ZX", "G43669FQ", "G50856PC", "G57776ZS", "G61256FT", "G69521XL", "G76417NN", "G78649WQ", "G82443XX", "G89827JR", "G90382BL", "G92275SC", "G92551JA", "G94106MV", "G49108TO" ], "uniprot_id": "P15529" }, "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "BACE1 is glycosylated; glycosylation may regulate activity.", "mechanism": "BACE1 cleaves APP to produce A\u03b2; upregulated in AMD and AD.", "protein": "BACE1 (Beta-secretase 1)", "protein_enriched": { "function": "Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generatio", "gene_name": "BACE1", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G80920RR", "G05724UK", "G06110VR", "G12398HZ", "G14023ZV", "G14669DU", "G15065YV", "G17689DH", "G21112KH", "G22310AV", "G22768VO", "G23863VK", "G25520XG", "G29880MM", "G39188ZX", "G44444MB", "G46687AB", "G49874UX", "G55220VL", "G60230HH", "G63889NK", "G64527OM", "G70101JE", "G70375MX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G80966KZ", "G84452RH", "G87618BG", "G90093AU", "G91636VS", "G93993PD", "G94854LT" ], "uniprot_id": "P56817" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390676" }, { "confidence": "medium", "disease": "Herpetic retinitis", "glycan_involvement": "Recognizes mannose 6-phosphate glycans on ligands/virions.", "mechanism": "Facilitates HSV-1 entry into RPE cells.", "protein": "Mannose 6-phosphate/IGF-II receptor", "protein_enriched": { "function": "Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:18817523, PubMed:2963003). Lysosomal enzymes bearing phosphomannosyl residue", "gene_name": "IGF2R", "glycan_count": 112, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G05049YU", "G08290VR", "G08918WF", "G11314AS", "G22310AV", "G23719VF", "G27058EU", "G28681TP", "G36379GD", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43669FQ", "G45395BF", "G46503DX", "G47644PP", "G47950XN", "G62765YT", "G65184UU", "G72747WU", "G75983OB", "G80920RR", "G88374WZ", "G90659AW", "G92275SC", "G95177YH", "G47012YE", "G01760ZU", "G02815KT", "G05724UK", "G06110VR", "G09724ZC", "G14260UH", "G25079LO", "G31852PQ", "G48584BU", "G64527OM", "G70101JE", "G83460ZZ", "G83633GK", "G00912UN", "G25418HZ", "G06356OH", "G15664MX", "G38663NM", "G59626AS", "G83646BJ", "G02528FI", "G04657PL", "G60033FS", "G72197KC", "G82463GQ", "G00273SJ", "G07246CJ", "G13131HA", "G27126ED", "G43223CG", "G46691LC", "G57776ZS", "G67031OU", "G70232NH", "G80075MS", "G83229XP", "G84452RH", "G87123QX", "G11629QQ", "G00406II", "G01650EU", "G25637MV", "G28541PG", "G39188ZX", "G40574BA", "G92050GC", "G93656SY", "G11870QZ", "G15169WU", "G25451PN", "G27915IV", "G47448YK", "G59324HL", "G62894KT", "G76417NN", "G79666IR", "G86880BF", "G87661QW", "G90382BL", "G93718GY", "G47748JZ", "G10819WX", "G14994KB", "G60177UT", "G77582RK", "G80223IX", "G81263BG", "G81315DD", "G93067EQ", "G95133RI", "G96577RX", "G48414YA", "G86500WE", "G14972EH", "G35029YA", "G49955PK", "G72790NZ", "G43417UB", "G10486CT", "G44215PV", "G70619PT", "G71125PP", "G26436YP" ], "uniprot_id": "P11717" }, "relationship_type": "causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Drusen formation", "glycan_involvement": "A\u03b2 derived from glycosylated APP; glycosylation may affect deposition.", "mechanism": "A\u03b2 is a major component of drusen, the hallmark of early AMD.", "protein": "Amyloid beta peptide (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390676" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation of E1 is essential for proper folding and function.", "mechanism": "Mediates viral entry into hepatocytes as part of the viral envelope.", "protein": "HCV E1", "relationship_type": "causal", "source_pmcid": "PMC12390683" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation of E2 shields epitopes from neutralizing antibodies.", "mechanism": "Mediates viral attachment and entry; key for immune evasion.", "protein": "HCV E2", "relationship_type": "causal", "source_pmcid": "PMC12390683" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Hypervariable regions and glycosylation enable immune escape.", "mechanism": "Persistent infection via immune evasion leads to chronic inflammation.", "protein": "HCV E2", "relationship_type": "causal", "source_pmcid": "PMC12390683" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation aids persistence and chronicity.", "mechanism": "Chronic infection triggers immune-mediated fibrosis.", "protein": "HCV E2", "relationship_type": "causal", "source_pmcid": "PMC12390683" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycan shielding supports viral persistence.", "mechanism": "Long-term infection increases risk of malignant transformation.", "protein": "HCV E2", "relationship_type": "causal", "source_pmcid": "PMC12390683" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation required for secretion and antigenicity.", "mechanism": "Surface antigen used for diagnosis and screening.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390683" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation modulates antibody accessibility.", "mechanism": "Targeted by neutralizing antibodies and vaccine candidates.", "protein": "HCV E2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390683" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation affects folding and immune recognition.", "mechanism": "Targeted by antiviral drug development.", "protein": "HCV E1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390683" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation impacts serological assay sensitivity.", "mechanism": "E2-specific antibodies indicate exposure/infection.", "protein": "HCV E2", "relationship_type": "biomarker", "source_pmcid": "PMC12390683" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycan shielding limits neutralization efficacy.", "mechanism": "Neutralizing antibodies against E2 can prevent infection.", "protein": "HCV E2", "relationship_type": "protective", "source_pmcid": "PMC12390683" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "KL-6 is a heavily O-glycosylated mucin; glycosylation affects its serum levels and detection.", "mechanism": "Elevated KL-6 reflects alveolar epithelial injury and predicts progression of PC19-PF.", "protein": "KL-6 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "ACE2 glycosylation modulates viral binding and receptor stability.", "mechanism": "SARS-CoV-2 binds ACE2 on AT2 cells, causing injury and downregulation, leading to pro-fibrotic signaling.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390685" }, { "confidence": "medium", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "ICAM-1 glycosylation affects cell adhesion and immune interactions.", "mechanism": "Elevated ICAM-1 correlates with endothelial injury and impaired gas exchange in PC19-PF.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "medium", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "VCAM-1 glycosylation modulates leukocyte adhesion.", "mechanism": "VCAM-1 elevation indicates vascular injury and correlates with persistent CT abnormalities.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "TGF-\u03b2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "TGF-\u03b2 drives fibroblast activation and ECM deposition, central to fibrotic remodeling.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12390685" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "Collagen glycosylation affects fibril formation and stability.", "mechanism": "Upregulated COL1A1 indicates active fibrogenesis and ECM accumulation.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "Glycosylation modulates collagen structure.", "mechanism": "Elevated COL3A1 reflects ongoing fibrotic remodeling.", "protein": "COL3A1", "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "medium", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "Collagen IV glycosylation affects matrix assembly.", "mechanism": "Serum COL4 is elevated in PC19-PF, indicating basement membrane remodeling.", "protein": "COL4", "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "medium", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "Laminin glycosylation is critical for cell-matrix interactions.", "mechanism": "Elevated laminin reflects ECM remodeling and fibrosis severity.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390685" }, { "confidence": "high", "disease": "Post-COVID-19 Pulmonary Fibrosis (PC19-PF)", "glycan_involvement": "Spike is heavily N-glycosylated; glycosylation shields epitopes and modulates infectivity.", "mechanism": "Spike protein mediates viral entry via ACE2, initiating epithelial injury and fibrotic cascade.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12390685" }, { "confidence": "medium", "disease": "Potential zoonotic infection", "glycan_involvement": "Glycosylation likely required for receptor binding and entry", "mechanism": "Mediates viral entry into human cells via NPC1 receptor", "protein": "M\u011bngl\u00e0 virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Innate immune suppression", "glycan_involvement": "No direct evidence of glycosylation involvement in immune suppression", "mechanism": "Blocks RIG-I signaling and IFN\u03b2 promoter activation by inhibiting IRF3 phosphorylation", "protein": "MLAV VP40", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "medium", "disease": "Potential zoonotic infection", "glycan_involvement": "No direct evidence; possible indirect effects via host glycoprotein interactions", "mechanism": "Impairment of host innate immunity may facilitate viral replication and pathogenesis", "protein": "MLAV VP40", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "low", "disease": "Filovirus hemorrhagic fever", "glycan_involvement": "No direct evidence", "mechanism": "Shares functional properties with MARV VP40, which is implicated in hemorrhagic fever pathogenesis", "protein": "MLAV VP40", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation critical for immune evasion and receptor binding", "mechanism": "Mediates viral entry and is essential for pathogenesis", "protein": "Ebola virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation important for function", "mechanism": "Mediates viral entry and pathogenesis", "protein": "Marburg virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "medium", "disease": "Innate immune suppression", "glycan_involvement": "No direct evidence", "mechanism": "Does not bind Keap1 or IMP\u03b1, thus lacks strong IFN suppression compared to EBOV/MARV VP24", "protein": "MLAV VP24", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Innate immune suppression", "glycan_involvement": "No direct evidence", "mechanism": "Blocks STAT1 nuclear import via IMP\u03b1 binding, suppressing IFN responses", "protein": "EBOV VP24", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Innate immune suppression", "glycan_involvement": "No direct evidence", "mechanism": "Binds Keap1, stabilizes Nrf2, upregulates antioxidant genes, modulates NF-\u03baB", "protein": "MARV VP24", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Innate immune suppression", "glycan_involvement": "No direct evidence", "mechanism": "Inhibits induction of IFN\u03b2 promoter, suppressing RIG-I signaling", "protein": "MLAV VP35", "relationship_type": "causal", "source_pmcid": "PMC12390687" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation required for proper folding and function", "mechanism": "Mediates membrane fusion for viral entry into host cells", "protein": "Nipah virus Fusion glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation supports receptor binding and antigenicity", "mechanism": "Binds to ephrin-B2/B3 receptors on host cells, enabling viral attachment", "protein": "Nipah virus Attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "medium", "disease": "Neurological disease (encephalitis)", "glycan_involvement": "Glycosylation may affect neurotropism", "mechanism": "Mediates entry into neurons expressing ephrin-B2/B3, leading to neuroinvasion", "protein": "Nipah virus Fusion glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "medium", "disease": "Neurological disease (encephalitis)", "glycan_involvement": "Glycosylation influences receptor interaction", "mechanism": "Facilitates viral targeting of CNS via ephrin-B2/B3 binding", "protein": "Nipah virus Attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "medium", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation required for function", "mechanism": "Enables viral entry into respiratory epithelial cells", "protein": "Nipah virus Fusion glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "medium", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation supports receptor binding", "mechanism": "Mediates attachment to respiratory tract cells via ephrin-B2/B3", "protein": "Nipah virus Attachment glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation maintains conformational epitopes", "mechanism": "Targeted by neutralizing antibodies (e.g., HENV-26/32), blocking fusion", "protein": "Nipah virus Fusion glycoprotein (F)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation maintains antigenicity", "mechanism": "Targeted by neutralizing antibodies, blocking receptor binding", "protein": "Nipah virus Attachment glycoprotein (G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Host glycosylation may affect receptor availability", "mechanism": "Serves as main entry receptor for NiV G protein", "protein": "Ephrin-B2 (EFNB2)", "relationship_type": "causal (host factor)", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Host glycosylation may affect receptor function", "mechanism": "Alternative entry receptor for NiV G protein, especially in CNS", "protein": "Ephrin-B3 (EFNB3)", "relationship_type": "causal (host factor)", "source_pmcid": "PMC12390688" }, { "confidence": "high", "disease": "Periprosthetic joint infection (PJI)", "glycan_involvement": "Glycosylation of surface proteins enhances biofilm formation and resistance.", "mechanism": "Surface glycoproteins mediate adhesion to prosthetic material, biofilm formation, and immune evasion.", "protein": "Staphylococcus epidermidis surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Inflammatory response", "glycan_involvement": "Glycosylated teichoic acids interact with host immune receptors.", "mechanism": "Acts as a pathogen-associated molecular pattern (PAMP) triggering host immune response.", "protein": "Lipoteichoic acid", "relationship_type": "causal", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Periprosthetic joint infection (PJI)", "glycan_involvement": "Glycosylation may mask antigenic sites.", "mechanism": "Contribute to bacterial survival and immune evasion.", "protein": "Membrane-embedded proteins (S. epidermidis)", "relationship_type": "causal", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation can modulate toxin activity and immune recognition.", "mechanism": "Exotoxins contribute to tissue damage and systemic inflammation.", "protein": "Secreted exotoxins (S. epidermidis)", "relationship_type": "causal", "source_pmcid": "PMC12390693" }, { "confidence": "high", "disease": "Periprosthetic joint infection (PJI)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in response to infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "high", "disease": "Periprosthetic joint infection (PJI)", "glycan_involvement": "Acute phase glycoproteins increase ESR.", "mechanism": "ESR is elevated in chronic infection due to increased plasma glycoproteins.", "protein": "Erythrocyte sedimentation rate (ESR) marker proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "AST elevation indicates liver involvement during therapy.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "ALP elevation reflects hepatic or bone involvement during infection/treatment.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Liver enzyme elevation", "glycan_involvement": "Glycosylation affects enzyme secretion and function.", "mechanism": "GGT elevation signals liver stress during therapy.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "medium", "disease": "Wound healing", "glycan_involvement": "CRP glycosylation status may influence its clearance.", "mechanism": "Normalization of CRP correlates with infection resolution and healing.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390693" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation modulates immune evasion and receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects antigenicity and host range.", "mechanism": "Hemagglutinin glycoprotein binds sialic acid on host cells, enabling viral entry.", "protein": "Influenza A virus hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "N-glycosylation influences fusion activity and immune recognition.", "mechanism": "Fusion glycoprotein enables viral fusion with host cell membrane.", "protein": "RSV fusion glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Glycoprotein D mediates viral entry via interaction with host receptors.", "protein": "HSV-1 glycoprotein D", "relationship_type": "causal", "source_pmcid": "PMC12390714" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "Glycosylation status affects tropism and immune response.", "mechanism": "Fiber protein binds to host cell receptors, initiating infection.", "protein": "Adenovirus fiber protein", "protein_enriched": { "function": "Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chapero", "gene_name": "L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04133" }, "relationship_type": "causal", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield impacts antibody accessibility.", "mechanism": "Spike glycoprotein is targeted by neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation sites modulate vaccine efficacy.", "mechanism": "Hemagglutinin is targeted by vaccines and antiviral drugs.", "protein": "Influenza A virus hemagglutinin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Fusion glycoprotein is targeted by monoclonal antibodies.", "protein": "RSV fusion glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390714" }, { "confidence": "medium", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosylation influences immunogenicity.", "mechanism": "Glycoprotein D is a target for vaccine development.", "protein": "HSV-1 glycoprotein D", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390714" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns may affect diagnostic assay sensitivity.", "mechanism": "Spike protein presence indicates active infection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12390714" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated; glycosylation modulates immunogenicity and antibody recognition.", "mechanism": "Target antigen for neutralizing antibody response in rVSV-based vaccines.", "protein": "SARS-CoV-2 Spike protein (JN.1 variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Vesicular stomatitis", "glycan_involvement": "Glycosylation required for proper folding and function; influences tissue tropism.", "mechanism": "Major virulence factor; mediates viral entry and neurotropism.", "protein": "VSV G protein", "relationship_type": "causal", "source_pmcid": "PMC12390721" }, { "confidence": "medium", "disease": "Neurological disorders (VSV-induced)", "glycan_involvement": "Glycosylation affects neuroinvasiveness.", "mechanism": "Neurotropism of G protein leads to CNS infection and neurotoxicity.", "protein": "VSV G protein", "relationship_type": "causal", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation critical for immunogenicity and vaccine efficacy.", "mechanism": "Used as antigen in VSV-vectored Ebola vaccine; induces protective immunity.", "protein": "Ebola virus glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Neurological disorders (VSV-induced)", "glycan_involvement": "Not glycosylated; attenuation via point mutations.", "mechanism": "Wild-type M protein induces cytotoxicity and host shut-off, contributing to neurotoxicity.", "protein": "VSV M protein", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (By similarity). In the endosome, the acidic pH induces", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P03524" }, "relationship_type": "causal", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No glycosylation; attenuation is via amino acid substitutions.", "mechanism": "Mutations attenuate VSV vector, reduce neurotoxicity, and enhance type I interferon response, improving vaccine safety.", "protein": "VSV M protein (mutant: M33A/M51R/V221F/S226R)", "relationship_type": "protective", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation sites modulate antibody accessibility.", "mechanism": "Neutralizing antibody titers against spike protein indicate vaccine efficacy.", "protein": "SARS-CoV-2 Spike protein (JN.1 variant)", "relationship_type": "biomarker", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation replaces G protein glycosylation, altering immunogenicity.", "mechanism": "Replacement reduces VSV neurotoxicity and enables COVID-19 vaccine development.", "protein": "VSV G protein (replaced by SARS-CoV-2 Spike)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Vesicular stomatitis", "glycan_involvement": "No glycosylation; effect is mutation-based.", "mechanism": "Attenuated M protein reduces virulence and host shut-off, improving safety for vaccine use.", "protein": "VSV M protein (mutant: M33A/M51R/V221F/S226R)", "relationship_type": "protective", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Neurological disorders (VSV-induced)", "glycan_involvement": "No glycosylation; attenuation via mutations.", "mechanism": "Mutations decrease neurotoxicity and mortality in animal models.", "protein": "VSV M protein (mutant: M33A/M51R/V221F/S226R)", "relationship_type": "protective", "source_pmcid": "PMC12390721" }, { "confidence": "high", "disease": "Witches\u2019 broom disease of blue palo verde", "glycan_involvement": "N-glycosylation at Asn239, Asn340, Asn401 may affect protein folding, viral assembly, and host interaction.", "mechanism": "PVBV GP is essential for viral infection and systemic spread in palo verde trees, leading to witches\u2019 broom symptoms.", "protein": "PVBV Glycoprotein (GP, P2)", "relationship_type": "causal", "source_pmcid": "PMC12390736" }, { "confidence": "medium", "disease": "High plains disease of maize and wheat", "glycan_involvement": "N-glycosylation predicted, facilitating host cell entry and immune evasion.", "mechanism": "HPWMoV GP mediates infection and spread in monocot hosts.", "protein": "HPWMoV Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390736" }, { "confidence": "medium", "disease": "Fig mosaic disease", "glycan_involvement": "N-glycosylation sites conserved, impacting viral infectivity.", "mechanism": "FMV GP required for infection and symptom development in fig trees.", "protein": "Fig Mosaic Virus Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390736" }, { "confidence": "high", "disease": "Witches\u2019 broom disease of blue palo verde", "glycan_involvement": "Glycosylation sites enable detection via molecular assays.", "mechanism": "Presence of PVBV GP RNA2 segment is a diagnostic marker for disease.", "protein": "PVBV Glycoprotein (GP, P2)", "relationship_type": "biomarker", "source_pmcid": "PMC12390736" }, { "confidence": "medium", "disease": "Witches\u2019 broom disease of blue palo verde", "glycan_involvement": "Glycosylation sites are potential targets for antiviral strategies.", "mechanism": "Targeting GP may disrupt viral assembly or host interaction.", "protein": "PVBV Glycoprotein (GP, P2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390736" }, { "confidence": "high", "disease": "Pleural Effusion", "glycan_involvement": "Glycosylation affects protein solubility and stability in pleural fluid.", "mechanism": "Elevated pleural fluid total protein indicates increased capillary permeability, distinguishing exudative from transudative effusions.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "high", "disease": "Pleural Effusion", "glycan_involvement": "LDH is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "High LDH in pleural fluid reflects cellular breakdown and inflammation, used in Light's criteria for exudate identification.", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation status may influence protein leakage.", "mechanism": "Exudative pleural effusions in tuberculosis show elevated total protein due to increased vascular permeability.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycoprotein content reflects inflammatory state.", "mechanism": "Parapneumonic exudates have high protein content from inflammatory exudation.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Malignancy (Lung Cancer)", "glycan_involvement": "Altered glycosylation in cancer may affect protein composition.", "mechanism": "Malignant pleural effusions are exudative with high protein due to tumor-induced vascular changes.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Congestive Cardiac Failure", "glycan_involvement": "Low glycoprotein content reflects non-inflammatory process.", "mechanism": "Transudative effusions in heart failure have low protein due to hydrostatic pressure imbalance.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Chronic Liver Disease", "glycan_involvement": "Reduced glycoprotein leakage due to non-inflammatory etiology.", "mechanism": "Transudative effusions in liver disease have low protein from hypoalbuminemia.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "ADA is a glycoprotein; glycosylation may affect its activity.", "mechanism": "Elevated ADA in pleural fluid is indicative of tuberculous pleuritis.", "protein": "Adenosine Deaminase (ADA)", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Nephrotic Syndrome", "glycan_involvement": "Low glycoprotein reflects protein loss.", "mechanism": "Transudative effusions in nephrotic syndrome have low protein due to hypoalbuminemia.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "medium", "disease": "Empyema Thoracis", "glycan_involvement": "High glycoprotein content from inflammatory exudate.", "mechanism": "Empyema is an exudate with high protein due to intense inflammation.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390823" }, { "confidence": "high", "disease": "Pancreatic Beta-cell Dysfunction", "glycan_involvement": "O-GlcNAcylation of target proteins regulates \u03b2-cell function.", "mechanism": "OGT sustains \u03b2-cell physiology by enhancing Pdx1-dependent mitogenesis, preserving insulin secretion.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC12391366" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Potential glycosylation affects receptor stability and mitophagy.", "mechanism": "PHB2 acts as a mitophagy receptor; its degradation by TIPE1 impairs mitophagy, exacerbating tubular injury.", "protein": "PHB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391366" }, { "confidence": "medium", "disease": "Pancreatic Beta-cell Dysfunction", "glycan_involvement": "Glycosylation may affect aggregation propensity.", "mechanism": "hIAPP aggregation promotes mitochondrial fragmentation and suppresses mitophagy, leading to \u03b2-cell damage.", "protein": "hIAPP", "relationship_type": "causal", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycation (non-enzymatic glycosylation) impairs GLO1 function.", "mechanism": "GLO1 detoxifies methylglyoxal; its suppression by glycation leads to OPA1/MFN1 downregulation and oxidative injury.", "protein": "GLO1", "relationship_type": "protective", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycation by CML impairs PON2 activity.", "mechanism": "Loss of PON2, glycated by CML, amplifies ER stress, inflammation, and mitochondrial fragmentation.", "protein": "PON2", "relationship_type": "protective", "source_pmcid": "PMC12391366" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycosylation may regulate channel function and mitophagy.", "mechanism": "VDAC1 sustains mitophagy and restrains NLRP3 inflammasome activation in retinal endothelial cells.", "protein": "VDAC1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycosylation status may affect MFN2 stability and fusion activity.", "mechanism": "Hypermethylation and acetylation suppress MFN2, impairing mitochondrial fusion and promoting vascular dysfunction.", "protein": "MFN2", "protein_enriched": { "function": "Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dyn", "gene_name": "MFN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95140" }, "relationship_type": "causal", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Glycosylation may modulate E3 ligase activity.", "mechanism": "Parkin-dependent mitophagy protects against mitochondrial dysfunction and cardiac injury.", "protein": "Parkin", "protein_enriched": { "function": "Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed", "gene_name": "PRKN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60260" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Glycosylation may affect kinase stability and mitophagy signaling.", "mechanism": "PINK1 initiates mitophagy; its downregulation leads to mitochondrial dysfunction in diabetic hearts.", "protein": "PINK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391366" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "N-glycosylation regulates chaperone activity and ER stress response.", "mechanism": "GRP78 upregulation promotes mitophagy and depletes antioxidant pool in pancreatic cells under glucotoxic conditions.", "protein": "GRP78 (BiP)", "relationship_type": "biomarker", "source_pmcid": "PMC12391366" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA recognizes terminal sialic acids (\u03b1-2,6 in humans, \u03b1-2,3 in avians) on host N-glycans.", "mechanism": "HA binds to host sialic acid-containing glycans to mediate viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Zoonotic influenza", "glycan_involvement": "Binding preference for \u03b1-2,3 or \u03b1-2,6 sialylated glycans influences cross-species transmission.", "mechanism": "HA glycan specificity determines host range and zoonotic potential.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Removes terminal sialic acids from host glycoproteins.", "mechanism": "NA cleaves sialic acids to facilitate viral release from host cells.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike protein binds to sialylated host glycans, possibly modulating entry.", "mechanism": "SARS-CoV-2 spike protein can engage host sialic acids during infection.", "protein": "Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "medium", "disease": "Ebola virus disease", "glycan_involvement": "Viral glycoproteins interact with host DC-SIGN via high-mannose glycans.", "mechanism": "Ebola virus uses DC-SIGN to facilitate entry into host cells.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialic acid-functionalized nanoparticles can inhibit HA binding.", "mechanism": "Blocking HA-glycan interaction can inhibit viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Strain-specific binding to \u03b1-2,6 or \u03b1-2,3 sialylated glycans.", "mechanism": "HA glycan binding specificity is used to characterize and differentiate influenza strains.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12391648" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Preference for di-LacNAc motifs in pandemic H1N1 strains.", "mechanism": "HA binding to longer polyLacNAc glycans enhances infection by some pandemic strains.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Cluster glycoside effect enhances inhibition of HA binding.", "mechanism": "Multivalent glycan presentation (e.g., on nanoparticles) can block HA-mediated infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391648" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binding to sialylated glycans may influence tissue tropism.", "mechanism": "Spike glycan interactions are used to study host adaptation and viral entry.", "protein": "Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12391648" }, { "confidence": "high", "disease": "Neural tube defects", "glycan_involvement": "SHH is a glycoprotein; glycosylation is required for its secretion and signaling.", "mechanism": "SHH glycoprotein secreted by floor plate cells is essential for neural tube patterning; defects cause neural tube malformations.", "protein": "Sonic hedgehog (SHH)", "protein_enriched": { "function": "The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-lengt", "gene_name": "SHH", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q15465" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation modulates SHH secretion and gradient formation.", "mechanism": "SHH signaling from floor plate progenitors is critical for dopaminergic neuron development; disruption linked to selective vulnerability in PD.", "protein": "Sonic hedgehog (SHH)", "protein_enriched": { "function": "The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-lengt", "gene_name": "SHH", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q15465" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Axon guidance disorders", "glycan_involvement": "Netrin-1 is glycosylated; glycosylation affects its stability and receptor interactions.", "mechanism": "Netrin-1 glycoprotein secreted by floor plate directs axonal trajectories; defects lead to miswiring.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation reported for EXOC5, but exocyst function is linked to trafficking of glycoproteins.", "mechanism": "EXOC5 upregulation in floor plate progenitors regulates primary cilia function, essential for SHH signaling and dopaminergic neuron fate; dysfunction may contribute to PD vulnerability.", "protein": "EXOC5", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Axon guidance disorders", "glycan_involvement": "SLIT2 is glycosylated; glycosylation is important for secretion and function.", "mechanism": "SLIT2 glycoprotein, secreted by floor plate, guides axons; disruption leads to guidance defects.", "protein": "SLIT2", "protein_enriched": { "function": "Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navig", "gene_name": "SLIT2", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G42124LM", "G80920RR", "G62765YT", "G41071NU", "G87661QW", "G83646BJ", "G79208PO", "G88520YF", "G37412TK", "G49906RN", "G65184UU", "G83460ZZ", "G49108TO" ], "uniprot_id": "O94813" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Axon guidance disorders", "glycan_involvement": "SLIT3 is glycosylated; glycosylation affects its function.", "mechanism": "SLIT3, like SLIT2, is involved in axon guidance from the floor plate.", "protein": "SLIT3", "protein_enriched": { "function": "Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navig", "gene_name": "SLIT1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "O75093" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "ATP2B2 is glycosylated; glycosylation affects membrane localization and function.", "mechanism": "ATP2B2 is a target of let-7b-5p; mitochondrial dysfunction involving ATP2B2 is implicated in PD.", "protein": "ATP2B2", "protein_enriched": { "function": "ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:15829536, PubMed:1723", "gene_name": "ATP2B2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G17863DS" ], "uniprot_id": "Q01814" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12392061" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement.", "mechanism": "MEST is highly expressed in midbrain floor plate and dopaminergic neurons; loss may contribute to PD.", "protein": "MEST (PEG1)", "protein_enriched": { "function": "", "gene_name": "MEST", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q5EB52" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Not a glycoprotein.", "mechanism": "LIN28A regulates let-7 miRNA processing; mutations cause dopaminergic neuron degeneration and PD phenotypes.", "protein": "LIN28A", "protein_enriched": { "function": "RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:21247876). Seems to recognize", "gene_name": "LIN28A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9H9Z2" }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Not a glycoprotein, but affects trafficking of glycoproteins.", "mechanism": "LRRK2 mutations affect primary cilia and vesicle trafficking, contributing to PD pathology.", "protein": "LRRK2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12392061" }, { "confidence": "high", "disease": "PARP inhibitor resistance", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Loss of PARP1 expression confers resistance to PARP inhibitors by reducing formation of cytotoxic PARP-DNA complexes.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "causal", "source_pmcid": "PMC12392133" }, { "confidence": "high", "disease": "PARP inhibitor resistance", "glycan_involvement": "ABCG2 is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "Downregulation of ABCG2 observed in resistant cell lines; ABCG2 normally exports PARPi drugs.", "protein": "ABCG2 (BCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "PARP inhibitor resistance", "glycan_involvement": "ABCB1 is a glycoprotein; glycosylation modulates drug efflux activity.", "mechanism": "No expression detected in Capan-1 cells; previously linked to PARPi resistance via drug efflux.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12392133" }, { "confidence": "high", "disease": "PARP inhibitor resistance", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Reversion mutations restore BRCA2 function and homologous recombination, leading to resistance.", "protein": "BRCA2", "protein_enriched": { "function": "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by ", "gene_name": "BRCA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G03238UC", "G37399XV", "G41247ZX", "G90382BL", "G49108TO" ], "uniprot_id": "P51587" }, "relationship_type": "causal", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "GLUT1 is N-glycosylated; glycosylation affects cell surface localization and glucose transport.", "mechanism": "Mutation in SLC2A1 found in PARPi-resistant cells; GLUT1 regulates glycolytic metabolism.", "protein": "SLC2A1 (GLUT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392133" }, { "confidence": "low", "disease": "PARP inhibitor resistance", "glycan_involvement": "COX4 is glycosylated; glycosylation may affect mitochondrial function.", "mechanism": "No significant change in protein expression; involved in oxidative phosphorylation pathway altered in resistance.", "protein": "COX4", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "COX4I1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13073" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "PARP inhibitor resistance", "glycan_involvement": "Beta-catenin is O-glycosylated; glycosylation can modulate signaling.", "mechanism": "Loss of beta-catenin and ABCG2 in resistant cells suggests Wnt pathway involvement in resistance.", "protein": "Beta-catenin (CTNNB1)", "relationship_type": "causal", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "Gemcitabine resistance", "glycan_involvement": "Wnt5a is glycosylated; glycosylation required for secretion and activity.", "mechanism": "High Wnt5a expression correlates with ABCG2 expression and gemcitabine resistance in PDAC.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "Cisplatin resistance", "glycan_involvement": "Wnt7b is glycosylated; glycosylation required for secretion and activity.", "mechanism": "Upregulation of Wnt7b increases ABCG2 via beta-catenin pathway, contributing to cisplatin resistance.", "protein": "Wnt7b", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway (By similarity). Plays an important role in embryonic deve", "gene_name": "WNT7A", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G85146YR" ], "uniprot_id": "O00755" }, "relationship_type": "causal", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "Gemcitabine resistance", "glycan_involvement": "Glycosylation affects ABCG2 function and drug efflux.", "mechanism": "ABCG2 expression correlates with gemcitabine resistance in PDAC.", "protein": "ABCG2 (BCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12392133" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "YKL-40 is a glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "YKL-40 is elevated in MASLD, reflecting inflammation and tissue remodeling.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "YKL-40 correlates with adiposity measures (BMI, trunk fat).", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Collagen IV is glycosylated, which affects its assembly and turnover.", "mechanism": "Serum collagen IV is increased in MASLD, reflecting extracellular matrix remodeling.", "protein": "Collagen type IV", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "P02462" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates collagen IV function.", "mechanism": "Collagen IV levels correlate with adiposity.", "protein": "Collagen type IV", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "P02462" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "PIIINP is glycosylated; glycosylation affects its secretion.", "mechanism": "PIIINP is elevated with increasing fibrosis, reflecting collagen III turnover.", "protein": "N-terminal propeptide of type III procollagen (PIIINP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation is required for YKL-40 function.", "mechanism": "YKL-40 is associated with tissue remodeling in fibrosis.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CK-18 is O-glycosylated, which may affect its stability and release.", "mechanism": "CK-18 and its fragments are released during hepatocyte apoptosis; highly elevated in MASLD.", "protein": "Cytokeratin 18 (CK-18)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "O-glycosylation may modulate CK-18 turnover.", "mechanism": "CK-18 is a marker of hepatocyte apoptosis, distinguishing MASH from simple steatosis.", "protein": "Cytokeratin 18 (CK-18)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "O-glycosylation may influence fragment release.", "mechanism": "CK-18 fragments correlate with fibrosis stage.", "protein": "Cytokeratin 18 (CK-18)", "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "PIIINP is higher in MASLD, reflecting increased collagen turnover.", "protein": "N-terminal propeptide of type III procollagen (PIIINP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392135" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Heparan sulfate glycosaminoglycan chains mediate growth factor/cytokine interactions", "mechanism": "Promote leukemic cell survival, proliferation, and adhesion to bone marrow niche", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12395219" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "O-glycosylation of mucin domains alters immune recognition", "mechanism": "Aberrant O-glycosylation shields AML cells from immune surveillance", "protein": "Mucin-1 (MUC1)", "relationship_type": "protective/causal", "source_pmcid": "PMC12395219" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may affect stability and apoptotic signaling", "mechanism": "Anti-apoptotic glycoprotein supporting AML cell survival; downregulated by isoimperatorin", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may modulate MYC activity", "mechanism": "Oncoprotein driving proliferation; downregulated by isoimperatorin", "protein": "MYC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "N-glycosylation required for receptor function", "mechanism": "Promotes AML cell growth and survival; downregulated by isoimperatorin", "protein": "IGF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may regulate kinase activity", "mechanism": "Kinase involved in migration and survival; suppressed by isoimperatorin", "protein": "PRKCA", "protein_enriched": { "function": "Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiati", "gene_name": "PRKCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17252" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation affects adhesion signaling", "mechanism": "Drives cell migration and adhesion; downregulated by isoimperatorin", "protein": "PTK2 (FAK)", "protein_enriched": { "function": "Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesi", "gene_name": "PTK2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q05397" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may modulate transcriptional activity", "mechanism": "Upregulated by isoimperatorin; enhances Th1/pro-inflammatory responses", "protein": "JUN", "protein_enriched": { "function": "Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcri", "gene_name": "JUN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P05412" }, "relationship_type": "protective", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may affect immune signaling", "mechanism": "Negative regulator of inflammation; upregulated by isoimperatorin", "protein": "NLRP12", "protein_enriched": { "function": "Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similar", "gene_name": "LSR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q86X29" }, "relationship_type": "protective", "source_pmcid": "PMC12395219" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation modulates chemokine receptor function", "mechanism": "Upregulated by isoimperatorin; promotes anti-tumor immune cell recruitment", "protein": "CXCR3", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling p", "gene_name": "CXCR3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49682" }, "relationship_type": "protective", "source_pmcid": "PMC12395219" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect stability and secretion.", "mechanism": "Elevated CSF GFAP reflects astrocytic reactivity and is associated with early AD pathology and cognitive decline.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "YKL-40 is heavily glycosylated; glycosylation is essential for its secretion and function.", "mechanism": "Higher CSF YKL-40 indicates astrocyte activation and is upregulated in response to AD pathology.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "S100B is glycosylated; glycosylation may modulate extracellular signaling.", "mechanism": "Elevated CSF S100B is linked to astrocyte stress and correlates with brain atrophy and cognitive impairment.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "sTREM2 is N-glycosylated; glycosylation affects its shedding and function.", "mechanism": "CSF sTREM2 reflects microglial activation; changes in levels are associated with AD progression and cognitive outcomes.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "Neurogranin is glycosylated; glycosylation may influence synaptic localization.", "mechanism": "Higher CSF neurogranin indicates synaptic degeneration, especially in AD risk carriers.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "Alpha-synuclein can be glycosylated; glycosylation may affect aggregation and toxicity.", "mechanism": "Increased CSF alpha-synuclein reflects synaptic loss and neuronal injury in AD progression.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "IL-6 is glycosylated; glycosylation is required for secretion and receptor binding.", "mechanism": "Rising CSF IL-6 indicates neuroinflammation associated with ageing and AD risk.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "NfL is glycosylated; glycosylation may affect stability and detection.", "mechanism": "Elevated CSF NfL reflects axonal injury and neurodegeneration in AD and ageing.", "protein": "NfL (NEFL)", "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation and pathology.", "mechanism": "Higher CSF p-tau181 is a hallmark of tau pathology and AD progression.", "protein": "p-tau181", "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau glycosylation affects its aggregation and neurotoxicity.", "mechanism": "Elevated CSF t-tau reflects neurodegeneration and is associated with AD risk.", "protein": "t-tau", "relationship_type": "biomarker", "source_pmcid": "PMC12395440" }, { "confidence": "high", "disease": "Classical homocystinuria (HCU)", "glycan_involvement": "Not directly discussed; CBS is predicted to be glycosylated but glycosylation not experimentally addressed in this article.", "mechanism": "CBS deficiency due to pathogenic mutations leads to impaired conversion of homocysteine to cystathionine, causing homocysteine accumulation.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Lens dislocation (ectopia lentis)", "glycan_involvement": "Not discussed.", "mechanism": "Elevated homocysteine due to CBS deficiency disrupts connective tissue integrity, leading to lens dislocation.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "medium", "disease": "Intellectual disability", "glycan_involvement": "Not discussed.", "mechanism": "Homocysteine accumulation from CBS deficiency affects neurological development.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "medium", "disease": "Premature osteoporosis", "glycan_involvement": "Not discussed.", "mechanism": "CBS deficiency leads to elevated homocysteine, which impairs bone metabolism.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Thromboembolic events", "glycan_involvement": "Not discussed.", "mechanism": "High homocysteine levels from CBS deficiency promote vascular damage and thrombosis.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "medium", "disease": "Marfanoid features", "glycan_involvement": "Not discussed.", "mechanism": "CBS deficiency and homocysteine accumulation affect connective tissue, resulting in Marfanoid habitus.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Classical homocystinuria (HCU)", "glycan_involvement": "Not discussed.", "mechanism": "CBS mutations (e.g., c.1006C>T, c.1061_1069del) serve as genetic biomarkers for HCU diagnosis.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "biomarker", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Classical homocystinuria (HCU)", "glycan_involvement": "Not discussed.", "mechanism": "CBS enzyme activity is targeted by vitamin B6, B12, folic acid, and betaine supplementation to lower homocysteine.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Classical homocystinuria (HCU)", "glycan_involvement": "Not discussed.", "mechanism": "CBS c.1006C>T (p.Arg336Cys) mutation alters protein conformation and reduces enzyme activity, causing HCU.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Classical homocystinuria (HCU)", "glycan_involvement": "Not discussed.", "mechanism": "CBS c.1061_1069del (p.Val354_Val356del) mutation disrupts protein folding and tetramer formation, abolishing enzymatic activity and causing HCU.", "protein": "Cystathionine beta-synthase (CBS)", "relationship_type": "causal", "source_pmcid": "PMC12395458" }, { "confidence": "high", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Hp glycosylation status affects oligomer structure and hemoglobin binding.", "mechanism": "Hp levels decrease post-exertion in ME, indicating impaired hemolysis buffering and oxidative stress response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "high", "disease": "Post-exertional malaise", "glycan_involvement": "Reduced glycosylation in Hp2-1 oligomers linked to diminished function.", "mechanism": "Hp2-1 phenotype and higher-mass oligomers associate with greater PEM severity.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "high", "disease": "Cognitive dysfunction", "glycan_involvement": "Altered glycosylation in Hp2-1 oligomers may impair neuroprotection.", "mechanism": "Lower baseline Hp levels and Hp2-1 phenotype correlate with worse cognitive performance post-exertion.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "medium", "disease": "Post-exertional malaise", "glycan_involvement": "Lower glycosylation in Hp2-1 forms reduces functional capacity.", "mechanism": "Hp2 allele confers vulnerability to PEM via reduced antioxidant capacity and impaired hemoglobin clearance.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "causal", "source_pmcid": "PMC12395708" }, { "confidence": "medium", "disease": "Post-exertional malaise", "glycan_involvement": "Hp1-1 dimer likely has optimal glycosylation for function.", "mechanism": "Hp1-1 phenotype is associated with milder PEM and cognitive resilience.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "protective", "source_pmcid": "PMC12395708" }, { "confidence": "medium", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Not specified.", "mechanism": "Upregulated post-exertion in ME, downregulated in controls, indicating ME-specific stress response.", "protein": "Alpha-2-HS-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "medium", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Not specified.", "mechanism": "Downregulated post-exertion in ME, upregulated in controls; may reflect vascular dysregulation.", "protein": "Fibulin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "low", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Not specified.", "mechanism": "Downregulated post-exertion in ME; may relate to altered extracellular matrix and vascular function.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "low", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Not specified.", "mechanism": "Upregulated post-exertion in controls, not in ME; suggests impaired heme clearance in ME.", "protein": "Hemopexin", "protein_enriched": { "function": "Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation", "gene_name": "HPX", "glycan_count": 236, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00875VP", "G00912UN", "G01650EU", "G02528FI", "G02886BB", "G04657PL", "G04854VP", "G05933EN", "G06247RL", "G06356OH", "G06853GH", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G14572XX", "G14994KB", "G15169WU", "G18647XP", "G20425TQ", "G22140GZ", "G22276PO", "G22310AV", "G22572EH", "G23294PN", "G23863VK", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G30769VJ", "G31118FR", "G31916IQ", "G36131WL", "G37818NZ", "G37868ZX", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G42358LZ", "G43223CG", "G44576HQ", "G45395BF", "G45504EY", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G47702MW", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55412XP", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G62165AG", "G63980BQ", "G64394MX", "G65019XG", "G66163OV", "G66621EA", "G68735SN", "G70232NH", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G72797UR", "G74772YG", "G75983OB", "G76417NN", "G78644BR", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82463GQ", "G82830MN", "G83555HU", "G84452RH", "G85144OK", "G86056PA", "G86182NS", "G86234IN", "G86752LQ", "G86795LJ", "G86880BF", "G87399DK", "G88374WZ", "G89205CJ", "G90093AU", "G90659AW", "G92135MA", "G92275SC", "G92406TI", "G94470IW", "G94917XT", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G00273SJ", "G14669DU", "G22768VO", "G60861FA", "G77669RF", "G89045VA", "G92551JA", "G57321FI", "G42962KI", "G44215PV", "G46687AB", "G60923RB", "G71146HJ", "G17015OC", "G29931IJ", "G43417UB", "G74722FL", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G01485JJ", "G02030ZB", "G10819WX", "G12745LE", "G14547CB", "G14972EH", "G15127JD", "G20528HD", "G20706XG", "G25418HZ", "G26915XM", "G27915IV", "G30248BL", "G30970QQ", "G31852PQ", "G31986NC", "G33416PL", "G35253PZ", "G37412TK", "G37509XX", "G37692EO", "G37995HC", "G39619TI", "G41071NU", "G43669FQ", "G43734MM", "G46524LG", "G54010QB", "G56284ZY", "G58087IP", "G58954YZ", "G60834IK", "G61256FT", "G62461SM", "G63381RX", "G67164EE", "G69521XL", "G71463BG", "G72398FA", "G72787SB", "G75798PH", "G76329HL", "G77547TA", "G78502KD", "G81124ET", "G81295CK", "G85269DF", "G85554PZ", "G85677PP", "G87389XI", "G89098OM", "G92081HT", "G98129XB", "G01160VV", "G05049YU", "G05724UK", "G05962QB", "G07246CJ", "G07755XJ", "G11911BT", "G12341GU", "G12579WK", "G15038BD", "G15664MX", "G17208MA", "G23505EP", "G30740WO", "G34989PA", "G35029YA", "G39188ZX", "G40206WX", "G41247ZX", "G44753VC", "G47950XN", "G49018RC", "G49642SA", "G49906RN", "G49955PK", "G56307ZW", "G59324HL", "G62765YT", "G64275UO", "G64527OM", "G68490OW", "G70101JE", "G70441OD", "G72790NZ", "G75418YA", "G76295SF", "G80920RR", "G83646BJ", "G84225JN", "G85282JO", "G87661QW", "G90734RJ", "G95977AE", "G96430BV" ], "uniprot_id": "P02790" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "low", "disease": "Myalgic encephalomyelitis", "glycan_involvement": "Not specified.", "mechanism": "Upregulated post-exertion in controls, not in ME; may indicate altered acute phase response.", "protein": "Inter-alpha-trypsin inhibitor heavy chain H4", "protein_enriched": { "function": "Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration", "gene_name": "ITIH4", "glycan_count": 191, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00912UN", "G03081ER", "G03382KH", "G08146BT", "G10486CT", "G22310AV", "G23863VK", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G48414YA", "G49874UX", "G56069TX", "G56903ZB", "G57818FI", "G59411JK", "G61937QU", "G68800OF", "G70418MS", "G72667IM", "G78261DB", "G84452RH", "G91636VS", "G95977AE", "G05724UK", "G06110VR", "G39188ZX", "G55220VL", "G64527OM", "G66676MI", "G80966KZ", "G82020ZR", "G02030ZB", "G03644CB", "G04854VP", "G05642HQ", "G05933EN", "G06192YD", "G06247RL", "G06356OH", "G08918WF", "G10256JP", "G10819WX", "G10846ZT", "G11629QQ", "G11911BT", "G12341GU", "G12793SR", "G13165FV", "G14547CB", "G14994KB", "G15169WU", "G15664MX", "G15828HX", "G16758MX", "G20076CD", "G24303GI", "G24954UD", "G26330YA", "G27058EU", "G27102CT", "G27126ED", "G27947YN", "G28681TP", "G31153XO", "G31916IQ", "G31986NC", "G32246SI", "G34617SM", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G47518TP", "G47737VJ", "G49018RC", "G51941GC", "G52527GH", "G54010QB", "G55412XP", "G56518TU", "G57776ZS", "G58087IP", "G59324HL", "G59536GA", "G59626AS", "G60070LT", "G60834IK", "G62765YT", "G63980BQ", "G64394MX", "G65186XA", "G65344XH", "G68209WQ", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72747WU", "G72797UR", "G75418YA", "G75983OB", "G77669RF", "G79939YZ", "G80075MS", "G81263BG", "G82830MN", "G83204BU", "G83213GG", "G83295QG", "G83633GK", "G85144OK", "G85269DF", "G85554PZ", "G86795LJ", "G86880BF", "G88325OQ", "G88374WZ", "G90093AU", "G90386IR", "G90659AW", "G91473PK", "G92081HT", "G93656SY", "G93860XO", "G94470IW", "G94917XT", "G95865ZB", "G99668VU", "G99950SF", "G31665QC", "G39595FH", "G44211QA", "G55216FT", "G60033FS", "G78166NF", "G87015RU", "G90789YQ", "G97876DH", "G17015OC", "G27391WQ", "G29068FM", "G43417UB", "G58001LT", "G57317CE", "G35029YA", "G53434XO", "G88713AC", "G74722FL", "G74724QE", "G27945LI", "G81006GJ", "G00273SJ", "G01650EU", "G14260UH", "G14972EH", "G20425TQ", "G22140GZ", "G22572EH", "G23294PN", "G23432EQ", "G36131WL", "G37412TK", "G39943KJ", "G43223CG", "G47748JZ", "G49906RN", "G50045TK", "G56238AO", "G58954YZ", "G60967DT", "G68490OW", "G69521XL", "G75798PH", "G78649WQ", "G78787DI", "G78790NZ", "G79568CQ", "G81295CK", "G84225JN", "G84820NF", "G86182NS", "G94120DZ" ], "uniprot_id": "Q14624" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395708" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike mediates viral entry into host cells via ACE2 binding.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "Bat coronavirus infection", "glycan_involvement": "N-glycosylation patterns influence host range and immune evasion.", "mechanism": "Spike enables bat coronavirus entry into bat host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans affect antibody accessibility and vaccine design.", "mechanism": "Target of neutralising antibodies and vaccines.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity/specificity.", "mechanism": "Detection of anti-spike antibodies indicates exposure or immunity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395742" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Conserved glycosylated epitopes in S2 subunit mediate cross-reactivity.", "mechanism": "Cross-neutralising antibodies from bat coronavirus exposure neutralise SARS-CoV-2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12395742" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N is less glycosylated; minor impact on immunogenicity.", "mechanism": "Anti-N antibodies indicate SARS-CoV-2 exposure.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans near RBD modulate antibody binding.", "mechanism": "RBD is main target for neutralising antibodies.", "protein": "Receptor Binding Domain (RBD) of Spike", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation affects host specificity and immune evasion.", "mechanism": "Spike mediates MERS-CoV entry into host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation shields epitopes from immune detection.", "mechanism": "Spike mediates SARS-CoV-1 entry into host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395742" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Conserved glycosylated S2 epitopes facilitate cross-neutralisation.", "mechanism": "Pre-existing cross-reactive antibodies (from bat CoV exposure) may confer partial protection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12395742" }, { "confidence": "high", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "P-glycoprotein is a glycosylated transporter; glycosylation affects its membrane localization and drug transport function.", "mechanism": "ABCB1 C3435T polymorphism increases P-glycoprotein activity, reducing clopidogrel absorption and efficacy, raising MACE risk after PCI.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation modulates P-glycoprotein stability and activity in cardiac tissues.", "mechanism": "ABCB1 C3435T genotype is associated with increased risk of CHD complications post-PCI.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation state may influence P-glycoprotein's response to hyperglycemic signaling.", "mechanism": "Hyperglycemia enhances P-glycoprotein phosphorylation via PKC pathway, further reducing clopidogrel bioavailability.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Altered glycosylation in diabetes may affect P-glycoprotein function.", "mechanism": "Diabetes correlates with increased P-glycoprotein activity, impacting drug absorption and cardiovascular risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12396218" }, { "confidence": "high", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Wild-type glycosylation pattern may support optimal transporter function.", "mechanism": "ABCB1 (CC) genotype combined with normoglycemia is protective against MACE in patients <75 years.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Mutant glycosylation may alter transporter activity under hyperglycemic conditions.", "mechanism": "ABCB1 (CT/TT) genotype combined with hyperglycemia increases risk of MACE after PCI.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12396218" }, { "confidence": "high", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Glycosylation is essential for P-glycoprotein's drug transport function.", "mechanism": "ABCB1 C3435T genotype is an independent risk factor for MACE in clopidogrel-treated PCI patients.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Modulating glycosylation could affect transporter activity.", "mechanism": "Targeting P-glycoprotein activity may improve clopidogrel efficacy and reduce MACE risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396218" }, { "confidence": "high", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Glycosylation differences may underlie genotype-specific transporter function.", "mechanism": "ABCB1 C3435T TT genotype associated with increased risk of MACE compared to CC genotype.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12396218" }, { "confidence": "medium", "disease": "Major Adverse Cardiac Events (MACE)", "glycan_involvement": "Disease states may alter glycosylation and transporter activity.", "mechanism": "ABCB1 C3435T genotype may interact with diabetes and hypertension to modulate MACE risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12396218" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "G is a glycoprotein; glycosylation is essential for receptor binding and immune evasion.", "mechanism": "G mediates host cell entry via ephrin-B2/B3 receptors; targeted by neutralizing monoclonal antibodies.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "F is glycosylated; glycosylation affects fusion activity and antigenicity.", "mechanism": "F mediates membrane fusion for viral entry; targeted by small-molecule inhibitors.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396924" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "No direct glycosylation reported for C; regulation is at translational level.", "mechanism": "C antagonizes interferon response and regulates viral replication; loss of C reduces virulence.", "protein": "Nipah virus C protein", "relationship_type": "causal", "source_pmcid": "PMC12396924" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "No direct glycosylation reported for P.", "mechanism": "P is essential for viral transcription and replication; alternative translation via leaky scanning.", "protein": "Nipah virus P protein", "protein_enriched": { "function": "", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9IH61" }, "relationship_type": "causal", "source_pmcid": "PMC12396924" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "No direct glycosylation reported for L.", "mechanism": "L is the viral polymerase; targeted by nucleoside analogs (remdesivir, favipiravir).", "protein": "Nipah virus L protein", "protein_enriched": { "function": "", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9IH60" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "fatal encephalitis", "glycan_involvement": "Glycosylation modulates receptor binding and neurotropism.", "mechanism": "G enables neuroinvasion via ephrin-B2/B3, leading to encephalitis.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "causal", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "respiratory disease", "glycan_involvement": "Glycosylation affects tropism and immune evasion.", "mechanism": "G mediates infection of respiratory tract cells.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "causal", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "No direct glycosylation; regulation is at RNA level.", "mechanism": "Translational control elements in C 5\u2032 UTR are druggable targets; ASOs suppress viral replication.", "protein": "Nipah virus C protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation influences antigenicity and detection.", "mechanism": "G is used for serological diagnosis and monitoring of infection.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "F is a target for diagnostic assays and immune monitoring.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396924" }, { "confidence": "high", "disease": "Advanced breast cancer", "glycan_involvement": "CD44 is a heavily glycosylated cell surface glycoprotein; glycosylation affects ligand binding and targeting.", "mechanism": "CD44 is overexpressed on breast cancer cells and targeted by hyaluronic acid-modified nanoparticles for drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Metastatic breast cancer", "glycan_involvement": "P-selectin is a glycoprotein; glycosylation modulates ligand recognition and cell adhesion.", "mechanism": "P-selectin-targeting peptides on nanoparticles enhance drug delivery to metastatic sites via platelet-mediated targeting.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "high", "disease": "Advanced breast cancer", "glycan_involvement": "HER2 is N-glycosylated; glycosylation influences receptor stability and antibody binding.", "mechanism": "HER2 is targeted by trastuzumab and nanoparticle-based delivery systems for HER2-positive breast cancer.", "protein": "HER2/neu (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Advanced breast cancer", "glycan_involvement": "Folate receptor is glycosylated; glycosylation affects ligand binding and endocytosis.", "mechanism": "Folate-modified nanoparticles target folate receptor alpha, overexpressed in some breast cancers, for drug delivery.", "protein": "Folate receptor alpha", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Lung metastatic breast cancer", "glycan_involvement": "CXCR4 is N-glycosylated; glycosylation modulates receptor function and ligand interaction.", "mechanism": "CXCR4 is targeted by nanoparticles to inhibit CXCL12-mediated lung metastasis of breast cancer cells.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "high", "disease": "Metastatic breast cancer", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect pharmacokinetics.", "mechanism": "Albumin-bound paclitaxel (Abraxane) improves drug delivery and efficacy in metastatic breast cancer.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "drug_carrier", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Locally advanced breast cancer", "glycan_involvement": "EGFR is N-glycosylated; glycosylation affects ligand binding and receptor activation.", "mechanism": "EGFR is targeted by gold nanoparticle-panitumumab conjugates for enhanced brachytherapy.", "protein": "Panitumumab target (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Advanced breast cancer", "glycan_involvement": "Exosome surface glycoproteins carry disease-specific glycan signatures.", "mechanism": "Exosome glycoproteins serve as biomarkers for diagnosis and monitoring of breast cancer progression.", "protein": "Exosome surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12397034" }, { "confidence": "medium", "disease": "Metastatic breast cancer", "glycan_involvement": "O-glycosylation of MUC1 is altered in cancer, exposing novel epitopes.", "mechanism": "MUC1 is overexpressed and aberrantly glycosylated in metastatic breast cancer, serving as a target for nanoparticle-based therapies.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "low", "disease": "Bone metastatic breast cancer", "glycan_involvement": "Integrins are glycosylated; glycosylation modulates ligand binding and cell adhesion.", "mechanism": "Integrin-targeted nanoparticles are used for imaging and therapy of bone metastases.", "protein": "Integrins (e.g., ITGA5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397034" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Defective N-glycosylation due to dolichol pathway dysfunction.", "mechanism": "Altered N-glycosylation leads to misfolding, aggregation, and amyloid plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Impaired N- and O-glycosylation affects tau folding and phosphorylation.", "mechanism": "Premature termination of N-glycosylation increases phosphorylated tau (pTau217), a marker for AD.", "protein": "Tau protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12397121" }, { "confidence": "high", "disease": "Anosmia", "glycan_involvement": "N-glycosylation required for olfactory enzyme activity.", "mechanism": "Loss of N-glycosylation impairs enzyme function, leading to anosmia.", "protein": "UDP-glucuronosyltransferase (UGT2A1)", "protein_enriched": { "function": "Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). May be involved in apoptosis regulation. Necessary f", "gene_name": "TCTN3", "glycan_count": 11, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G15664MX", "G46503DX", "G62765YT", "G65000LJ", "G72747WU", "G80920RR", "G83460ZZ", "G43734MM", "G63277FZ", "G90734RJ", "G72407SV" ], "uniprot_id": "Q6NUS6" }, "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates channel activity and neuronal signaling.", "mechanism": "Altered N-glycosylation affects channel function, contributing to neurodegeneration.", "protein": "Voltage-gated calcium channels", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for proper channel folding and function.", "mechanism": "Defective N-glycosylation alters channel properties, impacting neuronal excitability.", "protein": "Voltage-gated potassium channels (Kv1.3, Kv1.4, HERG)", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation essential for receptor assembly and activity.", "mechanism": "Altered N-glycosylation impairs receptor function, affecting neurotransmission.", "protein": "Nicotinic acetylcholine receptors", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Defective N-glycosylation disrupts receptor signaling.", "protein": "Muscarinic acetylcholine receptors", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for GPCR trafficking and function.", "mechanism": "Altered N-glycosylation affects GPCR signaling pathways.", "protein": "G protein-coupled receptors (GPCRs)", "relationship_type": "causal", "source_pmcid": "PMC12397121" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "O-glycosylation at Ser103 affects protein folding and activity.", "mechanism": "O-GlcNAcylation regulates Nrf2 activity, modulating antioxidant response.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397121" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "O-glycosylation modulates transcription factor activity.", "mechanism": "O-GlcNAcylation regulates NF-\u03baB activity, linking nutrient status to inflammation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397121" }, { "confidence": "high", "disease": "Oral cancer", "glycan_involvement": "CD44 is a glycoprotein; glycosylation affects ligand binding and cell adhesion", "mechanism": "CD44 overexpression is associated with higher T category (local tumor invasion/progression)", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "high", "disease": "Oral cancer", "glycan_involvement": "Glycosylation modulates CD44 interaction with hyaluronic acid and downstream signaling", "mechanism": "CD44 mediates drug resistance via cancer stem cell maintenance, drug efflux, DNA repair, and anti-apoptotic pathways", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma (OSCC)", "glycan_involvement": "Glycosylation influences CD44 stability and cell surface localization", "mechanism": "CD44 overexpression correlates with poor prognosis and decreased survival", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Variant-specific glycosylation enhances growth factor binding and matrix interactions", "mechanism": "CD44v6 promotes tumor invasion and epithelial-mesenchymal transition (EMT)", "protein": "CD44v6", "protein_enriched": { "function": "Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:197", "gene_name": "CD44", "glycan_count": 81, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G57321FI", "G53434XO", "G43417UB", "G48414YA", "G10486CT", "G00912UN", "G02030ZB", "G05962QB", "G06247RL", "G06330RB", "G06356OH", "G08918WF", "G11629QQ", "G13694XX", "G15169WU", "G20312EM", "G22310AV", "G23010ZW", "G24517ZG", "G25418HZ", "G25451PN", "G27058EU", "G27947YN", "G33791AF", "G37818NZ", "G37881RL", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G43223CG", "G44215PV", "G45395BF", "G46524LG", "G47012YE", "G47518TP", "G51413EV", "G52527GH", "G53075ES", "G55412XP", "G56784JY", "G57776ZS", "G57888GL", "G59324HL", "G59536GA", "G59626AS", "G60834IK", "G62461SM", "G64394MX", "G65019XG", "G66163OV", "G66760KM", "G69521XL", "G70232NH", "G70888PK", "G75983OB", "G76417NN", "G77547TA", "G77582RK", "G79666IR", "G80075MS", "G80223IX", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G86880BF", "G87123QX", "G90093AU", "G90382BL", "G91344EV", "G91473PK", "G94831VI", "G95133RI", "G96577RX", "G98611JV", "G56770VP", "G80920RR", "G71784JC", "G49108TO" ], "uniprot_id": "P16070" }, "relationship_type": "causal", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma", "glycan_involvement": "Glycosylation regulates CD44-mediated signaling pathways", "mechanism": "CD44 overexpression is associated with poor 5-year survival", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Glycosylation may affect tissue-specific interactions but not distant spread", "mechanism": "CD44 expression is not significantly associated with lymph node metastasis (N category)", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Detection cutoff and glycosylation heterogeneity may affect results", "mechanism": "No significant association between CD44 overexpression and histological grade", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Glycosylation status may not impact these invasion pathways", "mechanism": "No significant association with perineural, lymphatic, or blood vessel invasion", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Targeting glycosylated CD44 may disrupt CSC maintenance and drug resistance", "mechanism": "CD44-targeted therapies proposed to overcome treatment resistance", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397467" }, { "confidence": "low", "disease": "Oral cancer", "glycan_involvement": "Isoform-specific glycosylation may modulate function", "mechanism": "Associations with cancer progression suggested, but specific roles unclear", "protein": "CD44v3/CD44v8-10", "relationship_type": "biomarker", "source_pmcid": "PMC12397467" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "GLUT3 is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "GLUT3 overexpression accelerates glucose uptake and nucleotide synthesis, promoting CRC cell growth via the AMPK/CREB1/GLUT3 axis.", "protein": "GLUT3", "protein_enriched": { "function": "Facilitative glucose transporter (PubMed:26176916, PubMed:32860739, PubMed:9477959). Can also mediate the uptake of various other monosaccharides across the cell membrane (PubMed:26176916, PubMed:9477", "gene_name": "SLC2A3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11169" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12397687" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "HK2 is glycosylated; glycosylation may regulate its stability and activity.", "mechanism": "HK2 is upregulated by HIF1-\u03b1, amplifying glucose metabolism and providing energy for CRC cell growth.", "protein": "Hexokinase 2 (HK2)", "protein_enriched": { "function": "Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (PubMed:23185017, PubMed:26985301, Pub", "gene_name": "HK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52789" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "PKM2 is glycosylated; glycosylation may affect its oligomerization and activity.", "mechanism": "PKM2 overexpression promotes glycolysis, correlates with poor prognosis, lymph node metastasis, and tumor staging.", "protein": "Pyruvate kinase M2 (PKM2)", "protein_enriched": { "function": "Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618-1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "OGT catalyzes O-GlcNAcylation of target proteins, altering their function.", "mechanism": "OGT-mediated O-GlcNAcylation suppresses TCA cycle metabolism via the OGT-c-Myc-PDK2 axis, promoting CRC progression.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-GlcNAcylation of ACLY increases its activity and nuclear localization.", "mechanism": "ACLY senses elevated glucose via O-GlcNAc glycosylation, enhancing lipid synthesis and tumor cell proliferation.", "protein": "ATP-citrate lyase (ACLY)", "protein_enriched": { "function": "Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism", "gene_name": "ACLY", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53396" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-GlcNAcylation at specific serine/threonine residues modulates SRPK2 function.", "mechanism": "O-GlcNAc modification enhances SRPK2 nuclear localization, regulating de novo lipid synthesis and promoting CRC growth.", "protein": "SRPK2", "protein_enriched": { "function": "Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is invol", "gene_name": "SRPK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96SB4" }, "relationship_type": "causal", "source_pmcid": "PMC12397687" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "GLUT1 glycosylation affects its membrane trafficking and glucose transport activity.", "mechanism": "GLUT1 is a Warburg effect marker; high expression is associated with poor prognosis and increased glucose uptake.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397687" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "GSK-3 is glycosylated; glycosylation may regulate its kinase activity.", "mechanism": "GSK-3 correlates with tumor budding grade and PD-L1 levels, impacting immunotherapy response.", "protein": "Glycogen synthase kinase-3 (GSK-3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "GLUT5 glycosylation affects its function and cell surface expression.", "mechanism": "GLUT5-engineered CAR-T cells utilize fructose in glucose-restricted environments, enhancing anti-tumor activity.", "protein": "GLUT5", "protein_enriched": { "function": "Functions as a fructose transporter that has only low activity with other monosaccharides (PubMed:16186102, PubMed:17710649, PubMed:28083649, PubMed:29548810, PubMed:8333543). Can mediate the uptake o", "gene_name": "SLC2A5", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22732" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397687" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "MCT4 glycosylation influences its membrane localization and transporter activity.", "mechanism": "MCT4 is a Warburg effect marker; high expression is linked to increased lactate export and tumor aggressiveness.", "protein": "MCT4", "protein_enriched": { "function": "Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (PubMed:11101640, PubMed:23935841, PubMed:31719150). Plays a predominant role in L-lactate efflux from highly glycolytic", "gene_name": "SLC16A3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15427" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397687" }, { "confidence": "high", "disease": "Portal hypertension (PH)", "glycan_involvement": "VWF is a heavily glycosylated protein; glycosylation affects its plasma levels and function.", "mechanism": "Elevated plasma VWF levels are a surrogate marker for clinically significant portal hypertension.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397721" }, { "confidence": "medium", "disease": "Metabolic dysfunction\u2013associated steatohepatitis (MASH)", "glycan_involvement": "Altered glycosylation may affect VWF clearance and activity in liver disease.", "mechanism": "VWF levels are used as a surrogate for portal hypertension severity in MASH.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397721" }, { "confidence": "medium", "disease": "Alcohol-related liver disease (ALD)", "glycan_involvement": "Glycosylation modulates VWF function and its interaction with platelets/endothelium.", "mechanism": "VWF plasma levels are elevated in ALD and correlate with portal hypertension.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397721" }, { "confidence": "medium", "disease": "Viral hepatitis C (HCV)", "glycan_involvement": "Glycosylation status may influence VWF's role in HCV-related vascular changes.", "mechanism": "VWF is elevated in HCV-related portal hypertension and reflects endothelial dysfunction.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397721" }, { "confidence": "medium", "disease": "Porto-sinusoidal vascular liver disease (PSVD)", "glycan_involvement": "Glycosylation impacts VWF's stability and detection in plasma.", "mechanism": "VWF is used as a surrogate marker for portal hypertension in PSVD.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397721" }, { "confidence": "low", "disease": "Portal hypertension (PH)", "glycan_involvement": "Aberrant glycosylation may enhance VWF-mediated endothelial activation.", "mechanism": "VWF contributes to endothelial dysfunction, which is implicated in PH pathogenesis.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC12397721" }, { "confidence": "high", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "NF155 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against NF155 disrupt paranodal adhesion, leading to demyelination and neuropathy.", "protein": "Neurofascin 155 (NF155)", "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "CNTN1 is heavily glycosylated; glycan structures may modulate immune recognition.", "mechanism": "Autoantibodies against CNTN1 impair node/paranode integrity, causing neuropathy.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "CASPR1 glycosylation may influence antibody binding and pathogenesis.", "mechanism": "Autoantibodies against CASPR1 disrupt paranodal junctions, leading to demyelination.", "protein": "CASPR1", "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Glycosylation of neurofascin isoforms may affect immune response.", "mechanism": "Autoantibodies targeting multiple neurofascin isoforms cause severe neuropathy, often with cranial involvement.", "protein": "Pan-Neurofascin (pan-NF)", "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "medium", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Autoantibodies against NF186/140 contribute to nodal dysfunction and neuropathy.", "protein": "Neurofascin 186/140 (NF186/140)", "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "CNS demyelinating diseases", "glycan_involvement": "MOG is glycosylated; glycan epitopes may be immunogenic.", "mechanism": "CSF-restricted MOG autoantibodies are associated with extensive CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399800" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)", "glycan_involvement": "Claudin-5 is a glycoprotein; glycosylation may affect barrier function.", "mechanism": "Downregulation of claudin-5 by cytokines disrupts blood-CSF barrier, facilitating immune cell entry.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "IgG glycosylation affects effector function and immune activation.", "mechanism": "Intrathecal synthesis of total IgG and AN-specific autoantibodies correlates with cranial nerve/CNS involvement.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12399800" }, { "confidence": "medium", "disease": "Autoimmune nodopathy (AN)", "glycan_involvement": "Albumin is glycosylated; glycan status not directly implicated here.", "mechanism": "Elevated CSF albumin (Q Alb) indicates blood-CSF barrier dysfunction in AN.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399800" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "CNTN1 glycosylation may influence renal antigenicity.", "mechanism": "Anti-CNTN1 antibodies are associated with nephrotic syndrome in AN patients.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12399800" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Cyp2b10 is glycosylated for proper membrane localization and function.", "mechanism": "Upregulation of Cyp2b10 enhances hepatic lipid metabolism, reducing triglyceride accumulation and obesity risk.", "protein": "Cyp2b10", "relationship_type": "protective", "source_pmcid": "PMC12400129" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation supports Cyp2b10 stability and activity.", "mechanism": "Induction of Cyp2b10 by PJT root extract prevents hepatic steatosis via improved triglyceride hydrolysis.", "protein": "Cyp2b10", "relationship_type": "protective", "source_pmcid": "PMC12400129" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "Glycosylation required for Ces2a secretion and enzymatic activity.", "mechanism": "Ces2a upregulation increases triglyceride hydrolysis, preventing lipid accumulation in liver.", "protein": "Ces2a", "relationship_type": "protective", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates Ces2a function.", "mechanism": "Ces2a activity improves glucose metabolism and prevents insulin resistance.", "protein": "Ces2a", "relationship_type": "protective", "source_pmcid": "PMC12400129" }, { "confidence": "high", "disease": "Adipose inflammation", "glycan_involvement": "Saa3 glycosylation affects its stability and inflammatory signaling.", "mechanism": "Saa3 is upregulated in inflamed adipose tissue; PJT root extract reduces Saa3 expression, indicating reduced inflammation.", "protein": "Saa3", "relationship_type": "biomarker", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Impaired glucose metabolism", "glycan_involvement": "Glycosylation is essential for Adipsin secretion and activity.", "mechanism": "Adipsin promotes insulin secretion and adipose homeostasis; increased by PJT root extract.", "protein": "Adipsin", "relationship_type": "protective", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Adipose inflammation", "glycan_involvement": "Glycosylation influences Mmp3 secretion and matrix remodeling.", "mechanism": "Mmp3 is a marker of adipose tissue inflammation; downregulated by PJT root extract.", "protein": "Mmp3", "relationship_type": "biomarker", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "Glycosylation modulates Il-1\u03b2 secretion and activity.", "mechanism": "Il-1\u03b2 is a pro-inflammatory cytokine; reduced expression indicates decreased hepatic inflammation.", "protein": "Il-1\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects Saa1 stability and inflammatory function.", "mechanism": "Saa1 upregulation is associated with hepatic inflammation and NAFLD; PJT root extract reduces Saa1 expression.", "protein": "Saa1", "relationship_type": "biomarker", "source_pmcid": "PMC12400129" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation required for Fas enzymatic activity.", "mechanism": "Fas promotes fatty acid synthesis; downregulation by PJT root extract improves lipid profile.", "protein": "Fas", "relationship_type": "causal", "source_pmcid": "PMC12400129" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates AKT1 stability and signaling.", "mechanism": "AKT1 promotes cell survival and proliferation; L-mimosine inhibits AKT1, inducing apoptosis and cell cycle arrest.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects SRC localization and activity.", "mechanism": "SRC kinase drives tumor growth, metastasis, and drug resistance; L-mimosine binds SRC, potentially inhibiting its oncogenic activity.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation regulates EGFR ligand binding and activation.", "mechanism": "EGFR signaling promotes proliferation; identified as a hub gene in breast cancer network.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation may affect MAPK8 activity.", "mechanism": "MAPK8 (JNK) regulates apoptosis and cell cycle; L-mimosine binds MAPK8, possibly modulating these processes.", "protein": "MAPK8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "HER2-positive breast cancer", "glycan_involvement": "O-glycosylation influences PRKACA kinase activity.", "mechanism": "High PRKACA expression correlates with resistance to HER2-targeted therapy.", "protein": "PRKACA", "protein_enriched": { "function": "Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, Pub", "gene_name": "PRKACA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate BCL2L1 stability.", "mechanism": "BCL2L1 inhibits apoptosis; L-mimosine may modulate its activity to promote cell death.", "protein": "BCL2L1", "protein_enriched": { "function": "Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of th", "gene_name": "BCL2L1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07817" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects BCL2 function.", "mechanism": "BCL2 prevents apoptosis; targeting BCL2 can induce cancer cell death.", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates chaperone activity.", "mechanism": "HSP90AA1 stabilizes oncogenic proteins; inhibition may disrupt cancer cell survival.", "protein": "HSP90AA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation regulates integrin-mediated adhesion.", "mechanism": "ITGB2 involved in cell adhesion and migration; may contribute to metastasis.", "protein": "ITGB2", "protein_enriched": { "function": "Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGA", "gene_name": "ITGB2", "glycan_count": 51, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G27947YN", "G49755GI", "G60033FS", "G62765YT", "G80920RR", "G49108TO", "G00912UN", "G04657PL", "G05962QB", "G27058EU", "G28681TP", "G31852PQ", "G35541EV", "G41247ZX", "G45395BF", "G46503DX", "G51653BI", "G57776ZS", "G60834IK", "G70232NH", "G79666IR", "G81637OR", "G83460ZZ", "G84452RH", "G90659AW", "G93718GY", "G72747WU", "G02528FI", "G09831WQ", "G11629QQ", "G32788FZ", "G01650EU", "G02815KT", "G05724UK", "G11870QZ", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G47644PP", "G57776ZU", "G59924QI", "G63041LO", "G64527OM", "G65000LJ", "G72735IY", "G92406TI", "G95865ZB", "G96091TT" ], "uniprot_id": "P05107" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect HRAS membrane localization.", "mechanism": "HRAS activation drives proliferation and survival signaling.", "protein": "HRAS", "protein_enriched": { "function": "Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). ", "gene_name": "KRAS", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01116" }, "relationship_type": "causal", "source_pmcid": "PMC12400671" }, { "confidence": "medium", "disease": "Sickle Cell Disease", "glycan_involvement": "Glycosylation of LRG1 may influence its stability and interaction with angiogenic factors.", "mechanism": "LRG1 is associated with proangiogenic mediators and may reflect vascular remodeling and angiogenesis in sickle cell disease.", "protein": "Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12400887" }, { "confidence": "low", "disease": "Sickle Cell Disease", "glycan_involvement": "Altered glycosylation may affect LRG1's function in angiogenesis.", "mechanism": "LRG1 modulates angiogenesis, which is implicated in the pathophysiology of sickle cell disease; targeting LRG1 could affect disease progression.", "protein": "Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400887" }, { "confidence": "high", "disease": "XMEN disease", "glycan_involvement": "Defective N-glycosylation of immune receptors impairs T-cell activation.", "mechanism": "Loss-of-function mutations in MagT1 impair magnesium transport and N-glycosylation, leading to immunodeficiency.", "protein": "MagT1", "relationship_type": "causal", "source_pmcid": "PMC12400893" }, { "confidence": "high", "disease": "EBV-positive Hodgkin lymphoma", "glycan_involvement": "Altered glycosylation of immune receptors reduces anti-EBV responses.", "mechanism": "Impaired immune surveillance due to MagT1 deficiency increases susceptibility to EBV-driven lymphomas.", "protein": "MagT1", "relationship_type": "causal", "source_pmcid": "PMC12400893" }, { "confidence": "medium", "disease": "Autoimmune cytopenia", "glycan_involvement": "Aberrant glycosylation of immune cell surface proteins affects self-recognition.", "mechanism": "Defective MagT1 disrupts immune tolerance, promoting autoimmunity.", "protein": "MagT1", "relationship_type": "causal", "source_pmcid": "PMC12400893" }, { "confidence": "medium", "disease": "Autoimmune cytopenia", "glycan_involvement": "Glycosylation modulates CD20 surface expression and function.", "mechanism": "CD20+ B cells mediate autoantibody production in cytopenia.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400893" }, { "confidence": "high", "disease": "EBV-positive Hodgkin lymphoma", "glycan_involvement": "Glycosylation affects CD30 signaling and immune evasion.", "mechanism": "CD30 is highly expressed on Hodgkin/Reed-Sternberg cells.", "protein": "CD30", "relationship_type": "biomarker", "source_pmcid": "PMC12400893" }, { "confidence": "high", "disease": "EBV-positive Hodgkin lymphoma", "glycan_involvement": "Glycosylation of gp350 is essential for viral infectivity.", "mechanism": "gp350 mediates EBV entry into B cells, contributing to lymphomagenesis.", "protein": "EBV gp350", "relationship_type": "causal", "source_pmcid": "PMC12400893" }, { "confidence": "medium", "disease": "XMEN disease", "glycan_involvement": "N-glycosylation of CD3 is required for TCR signaling.", "mechanism": "CD3+ T cell dysfunction is characteristic of XMEN disease.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400893" }, { "confidence": "medium", "disease": "Autoimmune cytopenia", "glycan_involvement": "Glycosylation regulates CD19-mediated signaling.", "mechanism": "CD19+ B cells are involved in autoantibody production.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400893" }, { "confidence": "high", "disease": "OSCC", "glycan_involvement": "Complex, monosialylated, biantennary/bisecting N-glycan at N144; change is independent of protein level.", "mechanism": "Specific N-glycopeptide (#4) at site N144 is highly overexpressed (33-fold) in OSCC serum compared to controls.", "protein": "IGHA1", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "high", "disease": "OSCC", "glycan_involvement": "Hybrid/complex, sialylated and/or fucosylated N-glycans at N180; microheterogeneity is disease-specific.", "mechanism": "Three N-glycopeptides (#8, #9, #17) at site N180 show large, protein-independent expression changes (up to 8-fold) in OSCC serum.", "protein": "IGHG1", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "high", "disease": "OPSCC", "glycan_involvement": "Complex, fucosylated N-glycan at N176; expression is HPV and disease-stage dependent.", "mechanism": "N-glycopeptide (#18) at site N176 is highly overexpressed (28.6-fold) in stage III-IV HPV-positive OPSCC, but not in OSCC.", "protein": "IGHG2", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Complex N-glycan at N180; glycopeptide expression is disease-associated.", "mechanism": "N-glycopeptide (#5) at site N180 proposed as early diagnostic marker; overexpressed in colorectal cancer serum.", "protein": "IGHG1", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "medium", "disease": "OSCC", "glycan_involvement": "Double-sialylated complex N-glycans at N56; increased sialylation in OSCC.", "mechanism": "Two double-sialylated complex N-glycopeptides at site N56 show altered expression in OSCC serum.", "protein": "A1AG1", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "medium", "disease": "OSCC", "glycan_involvement": "Single/double sialylated, fucosylated complex N-glycans; increased complexity in OSCC.", "mechanism": "Three N-glycopeptides at a single site show altered sialylation/fucosylation in OSCC serum.", "protein": "IGHM", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "medium", "disease": "OSCC", "glycan_involvement": "Complex/hybrid N-glycans; increased sialylation/fucosylation in OSCC.", "mechanism": "Altered N-glycopeptide expression detected in OSCC serum.", "protein": "Haptoglobin (HPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "high", "disease": "HCC", "glycan_involvement": "Core-fucosylation of N-glycan; enhances diagnostic specificity.", "mechanism": "Core-fucosylated AFP is increased in HCC serum.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered core fucosylation and sialylation of N-glycans on PSA.", "mechanism": "Low core fucosylation and high \u03b12,3-sialic acid on PSA distinguish high-risk prostate cancer.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "medium", "disease": "OSCC", "glycan_involvement": "Complex N-glycans at N180; glycopeptide levels independent of protein abundance.", "mechanism": "Multiple N180-site glycopeptides (lectin-based study) overexpressed (>5-fold) in OSCC serum.", "protein": "IGHG1", "relationship_type": "biomarker", "source_pmcid": "PMC12402464" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Heavily glycosylated; glycosylation required for membrane localization and function.", "mechanism": "Associated with maintenance of cell membrane integrity and stemness; high expression predicts poor prognosis and recurrence.", "protein": "CD133 (Prominin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates ligand binding and cell adhesion.", "mechanism": "Involved in cell-cell interactions, adhesion, migration; anti-CD44 antibody inhibits tumor/metastatic growth.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402491" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects cell adhesion and signaling.", "mechanism": "EpCAM+ cells show high tumorigenicity and poor morphology; linked to stemness and poor prognosis.", "protein": "EpCAM (CD326)", "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "high", "disease": "Metastatic HCC", "glycan_involvement": "Glycosylation required for cell adhesion and signaling.", "mechanism": "CD90+ cells are highly metastatic; CD90+CD44+ cells form lung metastases.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "high", "disease": "Drug-resistant HCC", "glycan_involvement": "Glycosylation essential for enzymatic activity.", "mechanism": "CD13+ cells enriched after chemotherapy; inhibition by bestatin suppresses CSCs and sensitizes to drugs.", "protein": "CD13 (ANPEP)", "protein_enriched": { "function": "Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of var", "gene_name": "ANPEP", "glycan_count": 197, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G07246CJ", "G10019LZ", "G10486CT", "G10819WX", "G11314AS", "G14669DU", "G18647XP", "G23453IV", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G37509XX", "G38663NM", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G43089EG", "G48414YA", "G49018RC", "G49955PK", "G57776ZU", "G59626AS", "G59924QI", "G60033FS", "G62765YT", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G79666IR", "G80075MS", "G80920RR", "G85282JO", "G85554PZ", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92050GC", "G01160VV", "G02528FI", "G05049YU", "G05724UK", "G06247RL", "G06356OH", "G08918WF", "G12261QD", "G12341GU", "G13131HA", "G14110OQ", "G20528HD", "G23719VF", "G24528MX", "G25079LO", "G25637MV", "G27126ED", "G27947YN", "G29545VG", "G30970QQ", "G33791AF", "G35029YA", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G39188ZX", "G39471UU", "G40926MX", "G43223CG", "G43669FQ", "G43769HG", "G44753VC", "G47644PP", "G47702MW", "G49755GI", "G49906RN", "G50856PC", "G55132BD", "G57317CE", "G57776ZS", "G59536GA", "G60834IK", "G60967DT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G75568BH", "G76295SF", "G80479JV", "G83460ZZ", "G83646BJ", "G86182NS", "G88891KO", "G93718GY", "G95865ZB", "G96091TT", "G99679NM", "G04854VP", "G05962QB", "G17208MA", "G28622IK", "G49642SA", "G60923RB", "G61256FT", "G63136LV", "G77669RF", "G78787DI", "G92135MA", "G94470IW", "G99668VU", "G57321FI", "G04657PL", "G45395BF", "G45504EY", "G46691LC", "G51653BI", "G70418MS", "G84225JN", "G98611JV", "G43417UB", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G10846ZT", "G15664MX", "G29184RN", "G31028YV", "G33416PL", "G40574BA", "G40834TG", "G41840AI", "G07810QS", "G13694XX", "G14972EH", "G16125XL", "G20210JR", "G26330YA", "G30221QT", "G30740WO", "G34989PA", "G37881RL", "G43734MM", "G44215PV", "G53075ES", "G56518TU", "G57888GL", "G58087IP", "G69521XL", "G70223PD", "G70888PK", "G72291OX", "G73430PD", "G75983OB", "G81637OR", "G82830MN", "G84452RH", "G86795LJ", "G90382BL", "G94665LC", "G81124ET", "G89827JR", "G90093AU", "G92275SC", "G01485JJ", "G03644CB", "G07755XJ", "G30769VJ", "G32788FZ", "G34617SM", "G37995HC", "G41882MT", "G45526EA", "G46503DX", "G47012YE", "G52890YB", "G58954YZ", "G64394MX", "G73968GN", "G83633GK", "G94831VI", "G95046LV", "G95177YH", "G49108TO" ], "uniprot_id": "P15144" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402491" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Involved in cell adhesion and signaling; marker for CSCs.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects interaction with SIRP\u03b1 and immune evasion.", "mechanism": "Inhibits phagocytosis; reduction by 4-methylumbelliferone increases immune clearance of CSCs.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402491" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation required for cell surface expression.", "mechanism": "Associated with cell adhesion and signaling; marker for CSCs.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates immune cell binding.", "mechanism": "Involved in cell-cell interaction and immune response; marker for CSCs.", "protein": "ICAM1 (CD54)", "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation critical for ligand binding.", "mechanism": "Mannose receptor involved in carbohydrate endocytosis; marker for CSCs.", "protein": "MRC1 (CD206)", "relationship_type": "biomarker", "source_pmcid": "PMC12402491" }, { "confidence": "high", "disease": "Polymyositis", "glycan_involvement": "MHC I is N-glycosylated, affecting antigen presentation and immune recognition.", "mechanism": "Upregulated MHC I expression in muscle fibers correlates with T-cell mediated muscle inflammation.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "high", "disease": "Polymyositis", "glycan_involvement": "CD8 glycosylation modulates T-cell activation and migration.", "mechanism": "CD8+ T-cell infiltration in muscle tissue mediates cytotoxic damage.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Dystrophin is glycosylated, impacting membrane stability.", "mechanism": "Normal dystrophin expression excludes dystrophinopathy; altered expression indicates dystrophic pathology.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "N-glycosylation critical for laminin function in muscle basement membrane.", "mechanism": "Normal merosin expression excludes merosin-deficient congenital muscular dystrophy.", "protein": "Merosin (Laminin alpha-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation affects dysferlin membrane repair activity.", "mechanism": "Normal dysferlin expression excludes dysferlinopathy.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation required for sarcoglycan complex stability.", "mechanism": "Normal sarcoglycan expression excludes sarcoglycanopathies.", "protein": "Sarcoglycans", "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation modulates collagen VI assembly and ECM interactions.", "mechanism": "Normal collagen VI expression excludes collagen VI-related myopathies.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation influences caveolin-3 membrane localization.", "mechanism": "Normal caveolin-3 expression excludes caveolinopathies.", "protein": "Caveolin-3", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium cha", "gene_name": "CAV3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56539" }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "Polymyositis", "glycan_involvement": "Glycosylation affects CD68-mediated phagocytosis.", "mechanism": "CD68+ macrophage infiltration indicates active muscle inflammation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "medium", "disease": "HTLV-1-associated myelopathy/spastic paraparesis (HAM/TSP)", "glycan_involvement": "N-glycosylation modulates MHC I antigen presentation in neuroinflammation.", "mechanism": "Upregulated MHC I in CNS and muscle correlates with immune-mediated neuroinflammation.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12404636" }, { "confidence": "high", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation of GP is critical for antigenicity and immune recognition.", "mechanism": "GP-only vaccines elicit protective immunity against Marburg virus challenge.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "medium", "disease": "Marburg virus disease", "glycan_involvement": "VP40 is not a glycoprotein; no direct glycan involvement.", "mechanism": "Inclusion of VP40 in VLP vaccines does not enhance and may reduce protective efficacy at low doses.", "protein": "Marburg virus VP40 matrix protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation maintains conformational epitopes for neutralizing antibody responses.", "mechanism": "GP-only mRNA vaccines confer full protection even at low doses.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "protective", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation affects immune recognition and vaccine efficacy.", "mechanism": "Spike protein is the main antigen in COVID-19 vaccines.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Nucleoprotein is not a glycoprotein; no direct glycan involvement.", "mechanism": "Multiantigen vaccines including nucleoprotein broaden protection.", "protein": "SARS-CoV-2 nucleoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Human papillomavirus infection", "glycan_involvement": "Glycosylation supports VLP assembly and immunogenicity.", "mechanism": "L1 glycoprotein is the basis for VLP vaccines against HPV.", "protein": "HPV L1 glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation is important for antigenicity.", "mechanism": "HBsAg is used in VLP-based hepatitis B vaccines.", "protein": "HBV surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Hepatitis E", "glycan_involvement": "Glycosylation supports immunogenicity.", "mechanism": "HEV capsid protein forms VLPs for vaccine use.", "protein": "HEV capsid protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation patterns influence immune recognition.", "mechanism": "GP is the main antigenic determinant for immune response and vaccine design.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation is essential for GP function and infectivity.", "mechanism": "GP mediates viral entry and pathogenesis.", "protein": "Marburg virus glycoprotein (GP)", "protein_enriched": { "function": "Plays a role in the release of virion progenies by disrupting the host plasma membrane", "gene_name": "VP5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77DJ4" }, "relationship_type": "causal", "source_pmcid": "PMC12404766" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "YKL-40 is a secreted glycoprotein; glycosylation is essential for its stability and secretion.", "mechanism": "Blood DNA methylation in CHI3L1 (YKL-40 gene) correlates with CSF YKL-40 levels, reflecting glial activation and neuroinflammation in AD.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12405053" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects YKL-40's extracellular function and detection.", "mechanism": "CSF YKL-40 levels indicate glial activation and neuroinflammatory processes.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12405053" }, { "confidence": "medium", "disease": "Neuro-axonal damage", "glycan_involvement": "NfL is glycosylated, which may affect its stability and release.", "mechanism": "CSF NfL levels reflect axonal injury; blood DNA methylation signatures may associate with NfL levels.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12405053" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence NfL's detectability and function.", "mechanism": "Elevated CSF NfL is a marker of neurodegeneration in AD.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12405053" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation is required for YKL-40's biological activity.", "mechanism": "Targeting CHI3L1 DNA methylation may regulate YKL-40 levels and modulate neuroinflammation in AD.", "protein": "YKL-40", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12405053" }, { "confidence": "high", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Loss of N-glycosylation site (N66) impairs folding, stability, and lysosomal trafficking.", "mechanism": "Mutations in CTNS gene disrupt cystinosin function, leading to cystine accumulation in lysosomes.", "protein": "Cystinosin", "protein_enriched": { "function": "Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:15128704, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:3320", "gene_name": "CTNS", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "O60931" }, "relationship_type": "causal", "source_pmcid": "PMC12406699" }, { "confidence": "high", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Defective N-glycosylation leads to misfolding and increased degradation.", "mechanism": "Altered glycosylation state (immature oligomannose) correlates with disease phenotype.", "protein": "Cystinosin", "protein_enriched": { "function": "Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:15128704, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:3320", "gene_name": "CTNS", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "O60931" }, "relationship_type": "biomarker", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Reduced mono-sialylated and agalactosylated glycans; altered glycan peaks (GP25, GP27, GP44, S1 trait).", "mechanism": "Serum and IgG N-glycosylation patterns (especially sialylation and galactosylation) are altered in NC.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Binds \u03b2-galactosides on glycoproteins; altered glycosylation may affect galectin-3 signaling.", "mechanism": "Galectin-3 interacts with cystinosin, modulating inflammation in cystinotic cells.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Niemann\u2013Pick type C", "glycan_involvement": "Reduced GlcNAc branching impacts glycoprotein function and disease progression.", "mechanism": "Knockdown of Mgat5 alters N-glycan complexity, correlating with disease severity.", "protein": "Mgat5", "protein_enriched": { "function": "Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a glycoprotein or a glycolipid-", "gene_name": "FUT7", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q11130" }, "relationship_type": "causal", "source_pmcid": "PMC12406699" }, { "confidence": "high", "disease": "Fucosidosis", "glycan_involvement": "Defective degradation of fucosylated glycans causes autophagosome buildup.", "mechanism": "Impaired FUCA1 function leads to glycan accumulation and lysosomal dysfunction.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "causal", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Classical Galactosemia", "glycan_involvement": "Altered sialylation and galactosylation reflect disease state.", "mechanism": "Elevated FA2G1S1 glycans in plasma IgG indicate metabolic disturbance.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "MAN1B1-CDG", "glycan_involvement": "Altered N-glycan processing due to MAN1B1 deficiency.", "mechanism": "Shifts in agalactosylated/galactosylated IgG N-glycans ratios are observed.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Inflammation-sensitive glycosylation changes in IgG.", "mechanism": "Urine IgG titres are elevated in NC, reflecting systemic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12406699" }, { "confidence": "medium", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Correct N-glycosylation is required for protein stability and lysosomal localization.", "mechanism": "Restoration of cystinosin glycosylation and function is a target for gene/stem cell therapy.", "protein": "Cystinosin", "protein_enriched": { "function": "Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:15128704, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:3320", "gene_name": "CTNS", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "O60931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12406699" }, { "confidence": "high", "disease": "Hearing loss", "glycan_involvement": "GlycA measures N-acetyl groups on acute-phase glycoproteins, reflecting glycosylation changes during inflammation.", "mechanism": "Systemic low-grade inflammation (reflected by elevated GlycA) partially mediates the effect of high salt intake on increased risk of hearing loss.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12409307" }, { "confidence": "high", "disease": "Hearing loss", "glycan_involvement": "CRP is N-glycosylated; glycosylation modulates its stability and inflammatory activity.", "mechanism": "Elevated CRP, an acute-phase glycoprotein, partially mediates the association between high salt intake and hearing loss via chronic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Reflects glycosylation status of multiple acute-phase proteins.", "mechanism": "GlycA is a marker of systemic inflammation, which is a known risk factor for cardiovascular disease.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects CRP's function and clearance.", "mechanism": "CRP is a well-established marker of inflammation and cardiovascular risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Represents glycosylation changes in acute-phase proteins during inflammation.", "mechanism": "Elevated GlycA reflects chronic inflammation, which is associated with hypertension risk.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP elevation is linked to increased risk of hypertension via inflammatory pathways.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Reflects glycosylation status of acute-phase glycoproteins.", "mechanism": "GlycA is elevated in chronic inflammation, which is implicated in diabetes pathogenesis.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation affects CRP's stability and function.", "mechanism": "CRP is a marker of inflammation, which contributes to diabetes risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Targeting glycosylation of acute-phase proteins could modulate inflammatory response.", "mechanism": "Reducing systemic inflammation (lowering GlycA) may mitigate hearing loss risk associated with high salt intake.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12409307" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Modulating CRP glycosylation may affect its inflammatory properties.", "mechanism": "Interventions that lower CRP may reduce inflammation-mediated hearing loss risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12409307" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation modulates folding, receptor binding, and immune evasion.", "mechanism": "Mediates viral entry via ACE2 binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Primary antigen for vaccine and neutralizing antibody development.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Mutation adjacent to glycosylation sites may alter glycan shielding and protein stability.", "mechanism": "D614G mutation increases viral infectivity and transmission.", "protein": "Spike glycoprotein (S) D614G variant", "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Disrupted folding may affect glycosylation and surface expression.", "mechanism": "D614P and D614C mutations disrupt S protein synthesis, cleavage, and viral assembly, reducing infectivity.", "protein": "Spike glycoprotein (S) D614P/C variants", "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Potentially alters glycan processing near mutation site.", "mechanism": "D614N mutation enhances S protein stability and infectivity.", "protein": "Spike glycoprotein (S) D614N variant", "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns may distinguish variants.", "mechanism": "S protein mutations (e.g., D614G) are used for variant tracking and epidemiology.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield may affect drug accessibility.", "mechanism": "Target for antiviral drugs inhibiting viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12410178" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation may affect assembly efficiency.", "mechanism": "E protein involved in virus assembly and budding.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation may influence membrane localization.", "mechanism": "M protein critical for virion assembly.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutation may impact glycan shield and immune recognition.", "mechanism": "D614G mutation is a marker for dominant circulating strains.", "protein": "Spike glycoprotein (S) D614G variant", "relationship_type": "biomarker", "source_pmcid": "PMC12410178" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "High-titer MOG-IgG is highly specific for MOGAD and indicates autoimmune targeting of MOG on oligodendrocytes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12412035" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG may influence antibody binding and assay specificity.", "mechanism": "Low-titer MOG-IgG can be detected in a small subset of MS patients, but is not specific for MS and may confound diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12412035" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation state may affect assay cross-reactivity.", "mechanism": "Presence of MOG-IgG at low titer in MS patients requires careful interpretation to avoid misdiagnosis with MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential diagnosis marker", "source_pmcid": "PMC12412035" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Decreased galactosylation and altered bisection predict higher organ involvement.", "mechanism": "IgG1 galactosylation (Gal) and bisection (Bis) levels correlate with degree of organ involvement.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Altered bisection enhances predictive accuracy for organ involvement.", "mechanism": "IgG3/4 bisection (Bis) levels, especially combined with IgG1Gal, predict severity and multisystem involvement.", "protein": "anti-dsDNA IgG3/4", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "Decreased galactosylation and increased fucosylation linked to LN severity.", "mechanism": "Aberrant glycosylation modulates immune complex formation and complement activation, contributing to nephritis.", "protein": "anti-dsDNA IgG1", "relationship_type": "causal", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "SLE with gastrointestinal involvement", "glycan_involvement": "Increased fucosylation marks GI organ involvement.", "mechanism": "Upregulation of core fucosylation (Fuc) associated with GI involvement.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "SLE with cardiovascular involvement", "glycan_involvement": "Increased fucosylation in IgG1 linked to CV involvement.", "mechanism": "Elevated \u03b1\u22121,6-fucosylation correlates with cardiovascular manifestations.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Therapeutic modulation of galactosylation and bisection proposed.", "mechanism": "Restoring normal glycosylation may ameliorate immune dysregulation and reduce organ damage.", "protein": "anti-dsDNA IgG1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Higher fucosylation indicates increased disease activity.", "mechanism": "Fucosylation of IgG1 correlates with SLE disease activity.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Pairwise glycoform analysis enhances prediction of organ involvement.", "mechanism": "Combination of IgG1Gal and IgG3/4Bis best predicts multisystem involvement.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Specific glycoform pair correlates with organ-specific involvement.", "mechanism": "IgG1Gal and IgG3/4Bis combination predicts involvement of musculoskeletal, haematological, and urinary systems.", "protein": "anti-dsDNA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates effector functions and immune complex formation.", "mechanism": "Altered Fc glycosylation patterns (decreased Gal, increased Fuc) linked to SLE activity and progression.", "protein": "total IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12414148" }, { "confidence": "high", "disease": "ATP6AP1-CDG (Congenital Disorder of Glycosylation, type II)", "glycan_involvement": "Defective N- and O-glycosylation of multiple glycoproteins due to impaired Golgi acidification.", "mechanism": "Loss-of-function mutations in ATP6AP1 disrupt V-ATPase function, impairing acidification of intracellular compartments and glycoprotein processing.", "protein": "ATP6AP1 (Ac45)", "protein_enriched": { "function": "Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V0A2", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G46503DX", "G49108TO", "G01650EU", "G20210JR", "G23294PN", "G80920RR" ], "uniprot_id": "Q9Y487" }, "relationship_type": "causal", "source_pmcid": "PMC12414802" }, { "confidence": "high", "disease": "Immunodeficiency syndromes", "glycan_involvement": "Abnormal glycosylation of immunoglobulins and immune receptors.", "mechanism": "Impaired glycosylation affects immune cell function and antibody production.", "protein": "ATP6AP1 (Ac45)", "protein_enriched": { "function": "Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V0A2", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G46503DX", "G49108TO", "G01650EU", "G20210JR", "G23294PN", "G80920RR" ], "uniprot_id": "Q9Y487" }, "relationship_type": "causal", "source_pmcid": "PMC12414802" }, { "confidence": "high", "disease": "Liver dysfunction/hepatopathy", "glycan_involvement": "Abnormal glycosylation of hepatic proteins.", "mechanism": "Defective glycoprotein processing leads to hepatomegaly, elevated liver enzymes, and fibrosis.", "protein": "ATP6AP1 (Ac45)", "protein_enriched": { "function": "Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V0A2", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G46503DX", "G49108TO", "G01650EU", "G20210JR", "G23294PN", "G80920RR" ], "uniprot_id": "Q9Y487" }, "relationship_type": "causal", "source_pmcid": "PMC12414802" }, { "confidence": "high", "disease": "Neurological manifestations (seizures, intellectual disability)", "glycan_involvement": "Defective glycosylation of neuronal glycoproteins.", "mechanism": "Impaired glycosylation disrupts neuronal protein function and synaptic signaling.", "protein": "ATP6AP1 (Ac45)", "protein_enriched": { "function": "Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V0A2", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G46503DX", "G49108TO", "G01650EU", "G20210JR", "G23294PN", "G80920RR" ], "uniprot_id": "Q9Y487" }, "relationship_type": "causal", "source_pmcid": "PMC12414802" }, { "confidence": "high", "disease": "COG6-CDG (Congenital Disorder of Glycosylation, type II)", "glycan_involvement": "Defective N- and O-glycosylation.", "mechanism": "Mutations in COG6 disrupt Golgi glycosylation machinery, leading to multisystem disease.", "protein": "COG6", "protein_enriched": { "function": "Involved in ER-Golgi transport (PubMed:11929878). Also involved in retrograde (Golgi to ER) transport (PubMed:37711075)", "gene_name": "COG3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96JB2" }, "relationship_type": "causal", "source_pmcid": "PMC12414802" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "O-glycosylation of proteins, affecting cell adhesion and signaling.", "mechanism": "Part of a 3-gene glycan-related signature (GRGM-3) predicting poor disease-free survival.", "protein": "GALNT16", "relationship_type": "biomarker", "source_pmcid": "PMC12414962" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "O-glycosylation, modulating tumor microenvironment and immune evasion.", "mechanism": "Included in GRGM-3; high expression correlates with poor prognosis and increased EMT.", "protein": "GALNT15", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N7C6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12414962" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "GPI-anchor glycan modification, affecting cell signaling.", "mechanism": "Member of GRGM-3; contributes to GPI-anchor biosynthesis, influencing cell surface protein localization.", "protein": "PIGT", "relationship_type": "biomarker", "source_pmcid": "PMC12414962" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Indirect; TERC upregulation correlates with glycan dysregulation subtype.", "mechanism": "TERC overexpression is associated with shortest DFS when combined with high GRGM-3 score.", "protein": "TERC", "relationship_type": "biomarker", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "N-glycan sialylation, modulating cell-cell interactions and immune escape.", "mechanism": "Upregulated by HPV E6 protein; promotes sialylation, contributing to tumor progression.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Sulfation of glycosaminoglycans, affecting ECM structure.", "mechanism": "Loss of CHST14 locus in MG2 subtype may reduce glycan metabolism, possibly lowering aggressiveness.", "protein": "CHST14", "protein_enriched": { "function": "Ferritin receptor that mediates non-transferrin-dependent delivery of iron. Mediates cellular uptake of ferritin-bound iron by stimulating ferritin endocytosis from the cell surface with consequent ir", "gene_name": "SCARA5", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G80920RR", "G62765YT", "G83460ZZ" ], "uniprot_id": "Q6ZMJ2" }, "relationship_type": "protective", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "N-glycosylation, influencing receptor function.", "mechanism": "Loss in MG2 subtype; may decrease N-glycan branching, affecting tumor cell signaling.", "protein": "MGAT1", "relationship_type": "protective", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "O-glycosylation of proteoglycans.", "mechanism": "Loss in MG2 subtype; may reduce glycosylation of proteoglycans, impacting cell adhesion.", "protein": "B4GALNT7", "relationship_type": "protective", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosaminoglycan chain elongation.", "mechanism": "Loss in MG3 subtype; may impair heparan sulfate biosynthesis, affecting growth factor signaling.", "protein": "EXTL1", "protein_enriched": { "function": "Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-67 during mitosis, specifically interacts with PPP2R2D (PR55-delta) an", "gene_name": "ENSA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "O43768" }, "relationship_type": "protective", "source_pmcid": "PMC12414962" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Polysialylation of cell surface proteins.", "mechanism": "Hypomethylation and upregulation in MG1 subtype; may enhance polysialylation, promoting invasion.", "protein": "ST8SIA1", "relationship_type": "causal", "source_pmcid": "PMC12414962" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoprotein complexes at the membrane.", "mechanism": "Loss of dystrophin protein production leads to failure of DGC assembly at muscle membrane, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12415971" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DGC is composed of glycoproteins; glycosylation is essential for complex integrity.", "mechanism": "Absence of dystrophin disrupts DGC, impairing membrane stability and muscle function.", "protein": "Dystrophin Glycoprotein Complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12415971" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystroglycan is heavily glycosylated; glycosylation is critical for its binding and function.", "mechanism": "Dystroglycan requires dystrophin for membrane localization; loss of dystrophin impairs dystroglycan function.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12415971" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Complex contains glycoproteins; glycosylation affects membrane association.", "mechanism": "Sarcoglycan complex stability depends on dystrophin; loss leads to membrane fragility.", "protein": "Sarcoglycan Complex", "relationship_type": "causal", "source_pmcid": "PMC12415971" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Retains domains for glycoprotein complex binding.", "mechanism": "Micro-dystrophin gene therapy restores partial DGC function, improving muscle stability.", "protein": "Micro-dystrophin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12415971" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Partial DGC assembly via glycoprotein interactions.", "mechanism": "Internally deleted dystrophin retains partial function, resulting in milder phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12415971" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Capsid glycosylation may affect cell entry and tropism.", "mechanism": "AAV capsids deliver micro-dystrophin gene to muscle cells.", "protein": "Adeno-associated virus capsid proteins (VP1, VP2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12415971" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycoprotein interactions are partially preserved.", "mechanism": "Partially functional DGC maintains some membrane stability.", "protein": "Dystrophin Glycoprotein Complex (DGC)", "relationship_type": "protective", "source_pmcid": "PMC12415971" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy", "glycan_involvement": "Capsid glycosylation may influence immune response.", "mechanism": "High-dose AAV9 associated with vascular adverse events in gene therapy.", "protein": "Adeno-associated virus capsid proteins (VP1, VP2)", "relationship_type": "causal", "source_pmcid": "PMC12415971" }, { "confidence": "medium", "disease": "Spinal muscular atrophy (SMA)", "glycan_involvement": "Capsid glycosylation may affect immunogenicity.", "mechanism": "AAV9 used for gene therapy in SMA, but associated with thrombotic microangiopathy.", "protein": "Adeno-associated virus capsid proteins (VP1, VP2)", "relationship_type": "therapeutic_target/adverse effect", "source_pmcid": "PMC12415971" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "PLP is a glycoprotein; glycosylation is essential for its trafficking and function.", "mechanism": "PrEP treatment impairs oligodendrocyte maturation by reducing PLP trafficking to the cell surface, leading to myelination deficits.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "causal", "source_pmcid": "PMC12416199" }, { "confidence": "high", "disease": "Demyelinating disorders", "glycan_involvement": "Glycosylation affects PLP stability and membrane insertion.", "mechanism": "Reduced PLP expression indicates impaired myelination.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "biomarker", "source_pmcid": "PMC12416199" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APOE is glycosylated, which affects its lipid binding and receptor interactions.", "mechanism": "APOE4 allele increases AD risk; decreased secretion from astrocytes impairs lipid transport.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "LAMP1 is heavily glycosylated, critical for lysosomal function.", "mechanism": "PLP accumulates with LAMP1 in lysosomes in PrEP-treated oligodendrocytes, indicating lysosomal dysfunction.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "Demyelinating disorders", "glycan_involvement": "Gephyrin is glycosylated, which may affect synaptic clustering.", "mechanism": "Gephyrin in OPCs regulates myelination; gene disruption impairs OPC differentiation.", "protein": "Gephyrin", "relationship_type": "causal", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "Demyelinating disorders", "glycan_involvement": "Neuroligins are N-glycosylated, essential for synaptic function.", "mechanism": "Disruption impairs OPC differentiation and myelination.", "protein": "Neuroligin 3b (nlgn3b)", "relationship_type": "causal", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Claudin-5 is glycosylated, affecting tight junction integrity.", "mechanism": "Overexpression and mispatterning in mLV of Fmr1 KO mice; linked to ASD pathology.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "VE-cadherin is N-glycosylated, important for cell adhesion.", "mechanism": "Overexpression and mispatterning in mLV of Fmr1 KO mice; linked to ASD pathology.", "protein": "VE-cadherin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12416199" }, { "confidence": "high", "disease": "Niemann Pick Disease Type C1", "glycan_involvement": "NPC1 is N-glycosylated; glycosylation is critical for its function.", "mechanism": "Mutations in NPC1 glycoprotein cause cholesterol accumulation and neurodegeneration.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC12416199" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Flotillin is glycosylated, which may affect vesicle formation.", "mechanism": "Flotillin is used as a marker for extracellular vesicles in AD CSF.", "protein": "Flotillin", "relationship_type": "biomarker", "source_pmcid": "PMC12416199" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Serum AQP4-IgG titres increase during relapses and decrease during remission; \u22652-fold increase is associated with relapse risk.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may influence immune recognition and pathogenicity.", "mechanism": "AQP4-IgG antibodies are directly pathogenic, mediating astrocyte injury and demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation status may affect therapeutic antibody binding.", "mechanism": "Reduction of AQP4-IgG titres with immunosuppressive therapy correlates with remission.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418092" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity and antibody recognition.", "mechanism": "Serum MOG-IgG titres increase during relapses and decrease during remission; \u22652-fold increase is associated with relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation modulates immune response and antibody binding.", "mechanism": "MOG-IgG antibodies are implicated in demyelination, though pathogenic mechanisms may be heterogeneous.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation may affect therapeutic antibody efficacy.", "mechanism": "Reduction of MOG-IgG titres with immunosuppressive therapy correlates with remission and monophasic disease.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may influence antibody detection.", "mechanism": "Low or seronegative AQP4-IgG titres during remission are associated with monophasic disease course.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation affects antigenicity and serological detection.", "mechanism": "Seroreversion (loss of detectable MOG-IgG) is more frequent in monophasic MOGAD and predicts lower relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "High AQP4-IgG titres during remission predict relapsing disease and higher relapse risk.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation influences antibody binding and clearance.", "mechanism": "Rapid decline of MOG-IgG titres (\u22656-fold) after attack is associated with monophasic disease.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418092" }, { "confidence": "high", "disease": "IgG4-related disease (IgG4-RD)", "glycan_involvement": "Fc galactosylation often decreased; increased Fab glycosylation modulates function.", "mechanism": "Elevated serum IgG4 and tissue infiltration by IgG4+ plasma cells correlate with disease activity and organ involvement; possible direct or compensatory role in pathogenesis.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Autoimmune pancreatitis (AIP)", "glycan_involvement": "Altered glycosylation may affect antigen binding and immune regulation.", "mechanism": "IgG4 is elevated in serum and tissue; passive transfer induces pancreatic pathology in mice.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "Increased Fab glycosylation influences antigen binding and B cell signaling.", "mechanism": "IgG4 competes with IgE for allergen binding, suppresses mast cell/basophil activation, and correlates with successful immunotherapy.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "protective", "source_pmcid": "PMC12418560" }, { "confidence": "medium", "disease": "Eosinophilic oesophagitis", "glycan_involvement": "Not specified.", "mechanism": "High local and food-specific IgG4 associated with disease; pathogenic or protective role unclear.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker/possible causal", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Parasitic infection (Schistosoma, Wuchereria)", "glycan_involvement": "Not specified.", "mechanism": "IgG4 dampens inflammation, promotes immune tolerance, but may facilitate chronic infection by suppressing clearance.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Not specified.", "mechanism": "Tumor-associated B cells produce IgG4, restricting effector cell functions and correlating with poor prognosis.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12418560" }, { "confidence": "medium", "disease": "Pancreatic cancer (PDAC)", "glycan_involvement": "Not specified.", "mechanism": "IgG4 responses and Tfh2 cells linked to poor survival; IgG4 suppresses antitumor immunity.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12418560" }, { "confidence": "medium", "disease": "Cholangiocarcinoma", "glycan_involvement": "Not specified.", "mechanism": "IgG4+ B cell infiltration correlates with reduced cytotoxic T cells and increased Treg, facilitating immune evasion.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Thrombotic thrombocytopenic purpura (TTP)", "glycan_involvement": "Not specified.", "mechanism": "IgG4 autoantibodies target ADAMTS13, leading to loss of enzymatic activity and disease.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "causal", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Engineered glycosylation for reduced effector function.", "mechanism": "IgG4 format used to block IL-23 p19, curtailing inflammation with reduced Fc effector functions.", "protein": "Mirikizumab (anti-IL-23 p19 IgG4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418560" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoprotein complex; loss disrupts glycoprotein interactions.", "mechanism": "Mutations in DMD gene cause absence of dystrophin, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12418671" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Complex contains glycosylated proteins (dystroglycans, sarcoglycans) essential for membrane stability.", "mechanism": "Disruption of complex weakens sarcolemma, increasing susceptibility to damage.", "protein": "Dystrophin-associated glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12418671" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Highly glycosylated; glycan chains mediate ECM interactions.", "mechanism": "Loss of dystrophin impairs alpha-dystroglycan function in ECM binding.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12418671" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation required for membrane localization and stability.", "mechanism": "Disrupted linkage between cytoskeleton and ECM due to dystrophin loss.", "protein": "Beta-dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC12418671" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Retains domains for glycoprotein complex interaction.", "mechanism": "Gene therapy delivers \u00b5dys to restore partial function.", "protein": "Micro-dystrophin (\u00b5dys)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418671" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation critical for complex assembly and function.", "mechanism": "Loss of dystrophin destabilizes sarcoglycan complex, contributing to membrane fragility.", "protein": "Sarcoglycans", "relationship_type": "causal", "source_pmcid": "PMC12418671" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "CK is glycosylated; release indicates membrane compromise.", "mechanism": "Elevated plasma CK reflects ongoing sarcolemmal damage.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418671" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Antagonists reduce cardiac fibrosis and improve function.", "protein": "Mineralocorticoid receptor", "protein_enriched": { "function": "Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target ", "gene_name": "NR3C2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08235" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418671" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "ACE inhibitors reduce afterload and fibrosis in DMD cardiomyopathy.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418671" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Potential immunogenicity related to glycan structures.", "mechanism": "Immune response to \u00b5dys/AAV vector can trigger myocarditis.", "protein": "Micro-dystrophin (\u00b5dys)", "relationship_type": "adverse_effect", "source_pmcid": "PMC12418671" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "O-glycosylation of MUC2 is altered, affecting mucus barrier integrity.", "mechanism": "Reduced MUC2 and altered glycosylation correlate with active IBD and inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Altered O-glycosylation impacts barrier and immune evasion.", "mechanism": "Decreased MUC2 and mucus layer thinning associated with tumorigenesis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Enteric Infection (Citrobacter rodentium)", "glycan_involvement": "O-glycan removal exposes epithelium to pathogens.", "mechanism": "Excessive mucin degradation by A. muciniphila thins mucus, increasing susceptibility to infection.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "O-glycan fermentation yields beneficial metabolites.", "mechanism": "A. muciniphila-mediated mucin degradation produces SCFAs that promote mucus production and metabolic health.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "O-glycosylation supports barrier and metabolic signaling.", "mechanism": "A. muciniphila abundance correlates with improved glucose homeostasis and increased mucus barrier.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12418764" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "May interact with mucin glycans to modulate immune response.", "mechanism": "Oral administration of Amuc_1100 reduces tumorigenesis in mouse models.", "protein": "Amuc_1100", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418764" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Likely interacts with mucin glycan structures.", "mechanism": "Extracellular vesicles containing Amuc_2172 blunt tumor progression.", "protein": "Amuc_2172", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Graft Versus Host Disease (GVHD)", "glycan_involvement": "O-glycan degradation compromises barrier.", "mechanism": "Elevated A. muciniphila degrades MUC2, thinning mucus and increasing GVHD severity.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12418764" }, { "confidence": "medium", "disease": "Rotavirus Infection", "glycan_involvement": "Sialic acid and galactose residues on O-glycans act as viral decoys.", "mechanism": "A. muciniphila degrades mucin glycans, reducing mucus's ability to inhibit rotavirus binding.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12418764" }, { "confidence": "medium", "disease": "Helminth Infection", "glycan_involvement": "O-glycosylation supports mucus-mediated expulsion of parasites.", "mechanism": "A. muciniphila abundance increases with mucus production, reducing worm burden and enhancing goblet cell response.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12418764" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "O-glycosylation is essential for \u03b1-DAG function; hypo-glycosylation causes migration defects.", "mechanism": "Reduced glycosylated \u03b1-DAG impairs ECM integrity, leading to porous pial border and neuronal overmigration.", "protein": "\u03b1-dystroglycan (\u03b1-DAG)", "protein_enriched": { "function": "Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins (PubMed:15358", "gene_name": "Dlg4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G46503DX", "G49108TO" ], "uniprot_id": "Q62108" }, "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "high", "disease": "Classical lissencephaly (type 1)", "glycan_involvement": "Reelin is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "Reduced Reelin levels disrupt radial migration, causing cortical lamination defects.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "high", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "N- and O-glycosylation required for laminin network assembly.", "mechanism": "Loss of LAMA1 at the pial border leads to ECM disruption and neuronal overmigration.", "protein": "LAMA1", "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Altered RPSA disrupts laminin binding, affecting radial glia morphology and migration.", "protein": "RPSA", "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "N-glycosylation regulates integrin function and ECM binding.", "mechanism": "Disturbed ITGB1 spatial distribution impairs cell-ECM adhesion, contributing to migration disorder.", "protein": "ITGB1", "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "N-glycosylation required for laminin stability and ECM structure.", "mechanism": "Drop in LAMB1 in meningeal layers disrupts ECM, facilitating neuronal overmigration.", "protein": "LAMB1", "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "low", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "Glycosylation influences PEDF secretion and activity.", "mechanism": "Altered PEDF levels affect ECM signaling and migration.", "protein": "Serpinf1 (PEDF)", "protein_enriched": { "function": "GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking. Negati", "gene_name": "Gdi2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q61598" }, "relationship_type": "modulator", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Classical lissencephaly (type 1)", "glycan_involvement": "Indirect; CTNNB1 regulates glycoprotein expression.", "mechanism": "Stabilized CTNNB1 reduces Reelin, leading to migration defects.", "protein": "CTNNB1 (\u03b2-catenin)", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:15132997). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-t", "gene_name": "Ctnnb1", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G36379GD", "G62765YT" ], "uniprot_id": "Q02248" }, "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "Indirect; LIN28A regulates glycoprotein mRNA and translation.", "mechanism": "LIN28A overexpression alters ECM glycoprotein levels, causing migration disorder.", "protein": "LIN28A", "protein_enriched": { "function": "RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:21247876). Seems to recognize", "gene_name": "LIN28A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9H9Z2" }, "relationship_type": "causal", "source_pmcid": "PMC12419088" }, { "confidence": "medium", "disease": "Cobblestone lissencephaly (type 2)", "glycan_involvement": "Glycosylation required for Reelin function.", "mechanism": "Restored Reelin levels in LIN28A/CTNNB1 coactivation rescue some migration defects.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "protective", "source_pmcid": "PMC12419088" }, { "confidence": "high", "disease": "Leishmaniasis", "glycan_involvement": "Glycosylation is essential for GP63's surface localization and function.", "mechanism": "GP63 is a major surface glycoprotein that mediates parasite survival, macrophage entry, and immune evasion; inhibition blocks parasite uptake and transformation.", "protein": "Glycoprotein 63 (GP63)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Surface glycosylation mediates host-parasite interactions.", "mechanism": "GP63 facilitates parasite entry into skin macrophages; inhibition reduces lesion formation.", "protein": "Glycoprotein 63 (GP63)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Leishmaniasis", "glycan_involvement": "Indirect; FPPS activity affects glycoprotein prenylation and membrane targeting.", "mechanism": "FPPS is essential for isoprenoid biosynthesis and protein prenylation, critical for parasite survival; inhibition disrupts sterol metabolism and GTPase function.", "protein": "Farnesyl diphosphate synthase (FPPS)", "protein_enriched": { "function": "Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Leishmaniasis", "glycan_involvement": "Indirect; NMT modifies proteins that may be glycosylated and membrane-associated.", "mechanism": "NMT catalyzes myristoylation of proteins required for parasite membrane targeting and signaling; inhibition is lethal to Leishmania.", "protein": "N-myristoyltransferase (NMT)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Indirect; NMT targets may be glycoproteins.", "mechanism": "NMT is essential for Plasmodium spp. survival; inhibitors block parasite development.", "protein": "N-myristoyltransferase (NMT)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "medium", "disease": "African sleeping sickness", "glycan_involvement": "Indirect; NMT substrates may be glycoproteins.", "mechanism": "NMT is required for Trypanosoma brucei survival; inhibition disrupts critical protein trafficking.", "protein": "N-myristoyltransferase (NMT)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects protease activity and cell surface localization.", "mechanism": "GP63-like metalloproteases are implicated in tumor invasion and immune modulation.", "protein": "Glycoprotein 63 (GP63)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFZ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12419573" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Not directly specified.", "mechanism": "Strictinin inhibits viral entry and replication, possibly via FPPS inhibition.", "protein": "Strictinin (binds FPPS)", "relationship_type": "protective", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Leishmaniasis", "glycan_involvement": "Targets glycoprotein GP63 and enzymes affecting glycoprotein modification.", "mechanism": "Amentoflavone inhibits all three proteins, reducing parasite burden and lesion formation.", "protein": "Amentoflavone (binds GP63, FPPS, NMT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Indirect; NMT substrates may be glycoproteins.", "mechanism": "Hypericin inhibits NMT, reducing parasite load and improving lesions.", "protein": "Hypericin (binds NMT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12419573" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycoprotein acetyls are heavily N-glycosylated; glycan structures modulate their stability and inflammatory activity.", "mechanism": "Higher plasma glycoprotein acetyls levels are associated with increased inflammation, which is linked to higher cardiovascular risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12420231" }, { "confidence": "high", "disease": "Cardiometabolic risk", "glycan_involvement": "N-glycosylation affects plasma half-life and immune recognition.", "mechanism": "Elevated glycoprotein acetyls reflect systemic inflammation, a key component of increased cardiometabolic risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12420231" }, { "confidence": "high", "disease": "Colorectal carcinoma", "glycan_involvement": "N-glycosylation modulates EGFR stability and ligand binding.", "mechanism": "EGFR signaling drives proliferation and drug resistance; expression and phosphorylation altered by 3D culture and ECM composition.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12425351" }, { "confidence": "high", "disease": "Breast carcinoma", "glycan_involvement": "N-glycosylation affects HER2 dimerization and antibody binding.", "mechanism": "HER2 signaling supports proliferation and survival; 3D ECM context alters HER2 phosphorylation and trastuzumab sensitivity.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12425351" }, { "confidence": "high", "disease": "Breast carcinoma", "glycan_involvement": "N-glycosylation required for proper folding and drug efflux function.", "mechanism": "Upregulated in 3D culture via HIF-1, confers multidrug resistance.", "protein": "P-glycoprotein (MDR-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "N-glycosylation critical for VEGF secretion and receptor binding.", "mechanism": "VEGF upregulated in 3D culture under hypoxia, promotes angiogenesis and tumor growth.", "protein": "VEGF", "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Colorectal carcinoma", "glycan_involvement": "N-glycosylation influences secretion and activity.", "mechanism": "Elevated in 3D cultures, associated with invasiveness and EMT.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "N-glycosylation affects secretion and receptor interaction.", "mechanism": "Upregulated in 3D spheroids, promotes inflammation and angiogenesis.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Ewing sarcoma", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "Upregulated and phosphorylated in 3D culture, drives proliferation and survival.", "protein": "IGF-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Ovarian carcinoma", "glycan_involvement": "N-glycosylation modulates cell-cell adhesion.", "mechanism": "Loss in 3D spheroids marks EMT and increased invasiveness.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Colorectal carcinoma", "glycan_involvement": "N-glycosylation affects adhesion and migration.", "mechanism": "Gain in 3D organoids marks EMT and mesenchymal phenotype.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation influences secretion and immunodetection.", "mechanism": "Upregulated in 3D spheroids, reflects hepatic differentiation and tumor status.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12425351" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antibody binding and pathogenicity.", "mechanism": "AQP4-IgG autoantibodies target astrocytic AQP4, causing astrocytopathy and demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may modulate antigenicity and immune response.", "mechanism": "MOG-IgG autoantibodies target MOG on oligodendrocytes, leading to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12426438" }, { "confidence": "medium", "disease": "Optic Neuritis", "glycan_involvement": "Glycosylation may influence AQP4 localization and antibody accessibility.", "mechanism": "AQP4-IgG-mediated astrocyte injury in optic nerve leads to demyelination and visual loss.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "Optic Neuritis", "glycan_involvement": "Glycosylation of MOG may affect immune recognition and disease severity.", "mechanism": "MOG-IgG binding to MOG on myelin triggers optic nerve demyelination, especially bilateral/anterior.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "Longitudinally Extensive Transverse Myelitis (LETM)", "glycan_involvement": "Glycosylation may modulate AQP4 function and antibody binding.", "mechanism": "AQP4-IgG induces astrocyte loss and inflammation in spinal cord, causing LETM.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12426438" }, { "confidence": "medium", "disease": "Longitudinally Extensive Transverse Myelitis (LETM)", "glycan_involvement": "MOG glycosylation may influence immune response and lesion localization.", "mechanism": "MOG-IgG triggers demyelination in spinal cord, often in thoracic/lumbar/conus regions.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC12426438" }, { "confidence": "medium", "disease": "Area Postrema Syndrome", "glycan_involvement": "Glycosylation may affect AQP4 distribution in brainstem.", "mechanism": "AQP4-IgG targets dorsal medulla astrocytes, causing area postrema syndrome.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "Glycosylation status may impact antibody binding and therapy response.", "mechanism": "AQP4-IgG seropositivity guides immunosuppressive therapy (e.g., rituximab).", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)", "glycan_involvement": "Glycosylation may influence MOG antigenicity and treatment response.", "mechanism": "MOG-IgG seropositivity guides acute steroid therapy and prognosis.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12426438" }, { "confidence": "medium", "disease": "Optic Neuritis", "glycan_involvement": "Glycosylation may modulate MOG-IgG binding and clinical outcome.", "mechanism": "MOG-IgG positivity is associated with good recovery and lower disability in optic neuritis.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12426438" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Fc glycosylation (galactose, sialic acid) modulates effector function and inflammation", "mechanism": "IgG antibodies neutralize HIV and mediate Fc-dependent effector functions (ADCC, ADCP, ADCD)", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12426988" }, { "confidence": "high", "disease": "Chronic inflammation in HIV", "glycan_involvement": "Reduced anti-inflammatory glycans on Fc region", "mechanism": "Aberrant glycosylation (loss of galactose/sialic acid) increases pro-inflammatory activity", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "Microbial translocation", "glycan_involvement": "Glycosylation affects IgA stability and mucosal function", "mechanism": "IgA maintains mucosal barrier integrity, preventing microbial translocation and inflammation", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Indirect; affects antibody diversity and glycosylation profiles", "mechanism": "AID drives somatic hypermutation and class switch recombination for high-affinity anti-HIV antibodies", "protein": "AID", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Sialylated glycan ligands regulate CD22 function", "mechanism": "CD22 modulates B cell activation threshold, impacting antibody responses to HIV", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation affects FCRL4 surface expression and function", "mechanism": "FCRL4 overexpression in exhausted B cells impairs immune synapse formation and BCR signaling", "protein": "FCRL4", "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation modulates CD80 stability and interaction", "mechanism": "Downregulation impairs B\u2013T cell crosstalk, reducing antigen-specific responses", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "Autoimmunity", "glycan_involvement": "Not directly specified", "mechanism": "Estrogen upregulates Bcl-2, promoting survival of autoreactive B cells and increasing autoimmunity risk", "protein": "Bcl-2", "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Loss of galactosylation/sialylation increases inflammation", "mechanism": "Pro-inflammatory IgG glycan profiles contribute to cardiovascular risk in PLWH and estrogen-treated individuals", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12426988" }, { "confidence": "medium", "disease": "Menopausal symptoms in HIV", "glycan_involvement": "Galactosylation status as biomarker for estrogen deficiency", "mechanism": "Loss of galactosylated IgG glycans in post-menopausal women correlates with immune dysregulation", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12426988" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors the DGC, which contains glycoproteins essential for membrane stability.", "mechanism": "Loss-of-function mutations in DMD gene lead to absence of dystrophin, destabilizing sarcolemma and causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12428244" }, { "confidence": "high", "disease": "DMD Cardiomyopathy", "glycan_involvement": "DGC contains glycosylated proteins (e.g., dystroglycan) critical for extracellular matrix interactions.", "mechanism": "Disruption of DGC due to dystrophin deficiency impairs cardiomyocyte membrane integrity, leading to cardiac dysfunction.", "protein": "Dystrophin-Glycoprotein Complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Utrophin forms a glycoprotein complex similar to DGC.", "mechanism": "Upregulation of utrophin partially compensates for dystrophin loss, mitigating cardiac pathology.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC12428244" }, { "confidence": "high", "disease": "DMD Cardiomyopathy", "glycan_involvement": "GALGT2 catalyzes O-glycosylation of \u03b1-dystroglycan and other proteins, enhancing membrane stability.", "mechanism": "GALGT2 overexpression induces glycosylation of muscle proteins, upregulating utrophin, integrins, and laminins, improving cardiac function.", "protein": "GALGT2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Integrins are glycoproteins whose glycosylation affects function and localization.", "mechanism": "Upregulated by GALGT2, integrins improve cell-matrix adhesion and cardiac resilience.", "protein": "Integrin alpha7/beta1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Laminins are heavily glycosylated, which is essential for their structural role.", "mechanism": "GALGT2-induced expression of laminins supports extracellular matrix integrity and cardiac function.", "protein": "Laminin alpha4/alpha5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Agrin is a glycoprotein; glycosylation is important for its function.", "mechanism": "GALGT2 upregulates agrin, contributing to neuromuscular junction and cardiac tissue stability.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "protective", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Alpha-dystrobrevin is part of the DGC and interacts with glycosylated proteins.", "mechanism": "Loss of alpha-dystrobrevin exacerbates cardiac dysfunction in DMD models.", "protein": "Alpha-dystrobrevin", "protein_enriched": { "function": "Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromi", "gene_name": "HESX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX0" }, "relationship_type": "causal", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "DMD Cardiomyopathy", "glycan_involvement": "Alpha7-integrin is a glycoprotein; glycosylation affects its adhesive properties.", "mechanism": "Deficiency worsens cardiac pathology in DMD models.", "protein": "Alpha7-integrin", "protein_enriched": { "function": "Integrin alpha-7/beta-1 is the primary laminin receptor on skeletal myoblasts and adult myofibers. During myogenic differentiation, it may induce changes in the shape and mobility of myoblasts, and fa", "gene_name": "ITGA7", "glycan_count": 8, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G46503DX", "G62765YT", "G80920RR", "G00912UN", "G31852PQ", "G41247ZX", "G01650EU", "G28541PG" ], "uniprot_id": "Q13683" }, "relationship_type": "causal", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "DGC disruption affects glycoprotein-mediated conduction system integrity.", "mechanism": "Dystrophin deficiency leads to Purkinje fiber degeneration and conduction defects, increasing arrhythmia risk.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12428244" }, { "confidence": "medium", "disease": "Diffuse astrocytoma", "glycan_involvement": "Trisialylation increases functional diversity and cell interaction potential.", "mechanism": "Elevated in peritumoral tissue; may modulate neuronal interactions and tumor microenvironment.", "protein": "GT1(d18:1/18:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Diffuse astrocytoma", "glycan_involvement": "Trisialylated glycan chain affects cell signaling and adhesion.", "mechanism": "Highly expressed in peritumoral region; implicated in microenvironment modulation and tumor progression.", "protein": "GT1(d18:1/20:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Diffuse astrocytoma", "glycan_involvement": "Monosialylation facilitates cell-matrix interactions.", "mechanism": "Prominently expressed; associated with cellular adhesion and immune evasion.", "protein": "GM2(d18:1/16:2)", "relationship_type": "biomarker", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Tumor invasion", "glycan_involvement": "Disialylation modulates signaling pathways for invasion.", "mechanism": "Enhances tumor cell invasion and resistance to apoptosis.", "protein": "GD1(d18:1/16:0)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Apoptosis resistance", "glycan_involvement": "Disialylated glycan structure supports survival signaling.", "mechanism": "Linked to increased tumor invasion and apoptosis resistance.", "protein": "GD2(d18:1/20:0)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Immune suppression", "glycan_involvement": "Fucosylation and trisialylation modulate immune cell activity.", "mechanism": "Fucosylated ganglioside associated with enhanced tumorigenic potential and immune suppression.", "protein": "Fuc-GT3(d18:1/24:4)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Immune suppression", "glycan_involvement": "Fucosylation of disialylated core dampens immune response.", "mechanism": "Linked to immunosuppressive effects in tumor microenvironment.", "protein": "Fuc-GD1(d18:1/18:2)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Cellular adhesion", "glycan_involvement": "Monosialylated glycan mediates cell-cell and cell-matrix interactions.", "mechanism": "Strongly linked to immune evasion and cell adhesion in peritumoral tissue.", "protein": "GM1(d18:1/18:1)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "low", "disease": "Tumor microenvironment modulation", "glycan_involvement": "High sialylation alters matrix interactions.", "mechanism": "Tetrasialylated ganglioside may contribute to extracellular matrix remodeling.", "protein": "GQ1(d18:1/16:3)", "relationship_type": "causal", "source_pmcid": "PMC12428295" }, { "confidence": "medium", "disease": "Diffuse astrocytoma", "glycan_involvement": "Trisialylated b-series structure influences cell signaling.", "mechanism": "Identified as a dominant isomer in peritumoral tissue; may reflect tumor-specific glycosylation.", "protein": "GT1b(d18:1/20:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12428295" }, { "confidence": "high", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "N-glycosylation at Asn196 and Asn318 modulates immune evasion and virulence.", "mechanism": "E2 mediates receptor binding, determines cellular tropism, and is the main antigenic target driving disease manifestation.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "high", "disease": "Chronic arthritis", "glycan_involvement": "Glycan shielding at N196/N318 facilitates immune evasion and persistence.", "mechanism": "E2 receptor-binding domains direct viral replication in joint tissues, contributing to persistent inflammation.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "medium", "disease": "Neurovirulent disease", "glycan_involvement": "Loss of glycosylation enhances heparan sulfate binding and neurovirulence.", "mechanism": "E2 mutations alter neuroinvasiveness and host adaptation, influencing disease severity.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "high", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "N-glycosylation at Asn139 and Asn245 is essential for folding, transport, and virulence.", "mechanism": "E1 mediates pH-dependent membrane fusion required for viral entry and infection.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "medium", "disease": "Chronic arthritis", "glycan_involvement": "Glycosylation at N139/N245 supports virulence and tissue tropism.", "mechanism": "E1 fusion activity enables infection of joint tissues, contributing to chronic disease.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "high", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "No direct glycosylation; immune modulation via protein-protein interactions.", "mechanism": "Capsid protein packages RNA and interacts with E2 for virion assembly; inhibits IRAK1 for immune evasion.", "protein": "Capsid protein", "protein_enriched": { "function": "Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers ", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03315" }, "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "high", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "Glycan shielding affects antibody accessibility.", "mechanism": "E2 is the main target for neutralizing antibodies and vaccine development.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12428335" }, { "confidence": "medium", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "Glycosylation influences immunogenicity.", "mechanism": "E1 fusion loop and Domain III are targets for fusion inhibitors and pan-protective antibodies.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12428335" }, { "confidence": "medium", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "Acts as chaperone; no direct glycosylation role.", "mechanism": "E3 facilitates proper spike assembly and maturation, essential for infectivity.", "protein": "E3 protein", "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "medium", "disease": "Sindbis fever (Pogosta/Ockelbo/Karelian disease)", "glycan_involvement": "No direct glycosylation; impacts glycoprotein maturation.", "mechanism": "6K modulates membrane permeability and glycoprotein processing, facilitating viral budding.", "protein": "6K protein", "relationship_type": "causal", "source_pmcid": "PMC12428335" }, { "confidence": "high", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "vWF is a heavily glycosylated protein; glycosylation affects its secretion and function.", "mechanism": "Elevated baseline vWF indicates pre-existing endothelial activation/dysfunction in HFrEF.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "high", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "ANG2 is glycosylated, which is important for its secretion and stability.", "mechanism": "Elevated baseline ANG2 reflects chronic endothelial activation in HFrEF.", "protein": "Angiopoietin 2", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "high", "disease": "Postoperative Hemodynamic Instability", "glycan_involvement": "Glycosylation modulates vWF release from endothelium.", "mechanism": "Dampened postoperative vWF response is associated with increased noradrenaline requirement and instability.", "protein": "von Willebrand Factor", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12428422" }, { "confidence": "high", "disease": "Vasoplegia", "glycan_involvement": "Glycosylation affects vWF multimerization and endothelial release.", "mechanism": "Blunted vWF increase post-CPB predicts susceptibility to vasoplegia.", "protein": "von Willebrand Factor", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12428422" }, { "confidence": "medium", "disease": "Postoperative Hemodynamic Instability", "glycan_involvement": "Glycosylation required for ANG2 function.", "mechanism": "ANG2 peaks postoperatively, reflecting endothelial stress and correlating with instability.", "protein": "Angiopoietin 2", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "medium", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "Heavily glycosylated proteoglycan; glycosaminoglycan chains are shed during injury.", "mechanism": "CD138 levels reflect glycocalyx degradation; peaks after CPB in both groups.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "medium", "disease": "Postoperative Hemodynamic Instability", "glycan_involvement": "Shedding of glycosaminoglycan chains marks glycocalyx breakdown.", "mechanism": "CD138 increase indicates endothelial glycocalyx injury post-CPB.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "low", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "Glycosylation required for P-Selectin function.", "mechanism": "No significant difference in sP-Selectin between groups; not a key marker here.", "protein": "P-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "low", "disease": "Postoperative Hemodynamic Instability", "glycan_involvement": "Glycosylation required for P-Selectin function.", "mechanism": "sP-Selectin levels unchanged post-CPB; not associated with instability.", "protein": "P-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12428422" }, { "confidence": "medium", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "Glycosylation affects vWF's adhesive properties and clearance.", "mechanism": "Chronic EC activation and vWF dysregulation contribute to endothelial dysfunction in HFrEF.", "protein": "von Willebrand Factor", "relationship_type": "causal", "source_pmcid": "PMC12428422" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "O-glycosylation in mucin-like domain stabilizes CD93 surface expression, essential for function in tumor vessels.", "mechanism": "CD93 is overexpressed in tumor-associated vasculature, promoting pathological angiogenesis and poor prognosis; targeting CD93 improves vascular function and immunotherapy efficacy.", "protein": "CD93", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12428824" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Shedding of glycosylated CD93 increases sCD93 in serum during inflammation.", "mechanism": "Elevated serum soluble CD93 (sCD93) correlates with asthma exacerbation and severity; sCD93 levels decrease after treatment.", "protein": "CD93", "relationship_type": "biomarker", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation enables sCD93 function as an opsonin and inflammatory mediator.", "mechanism": "sCD93 levels are elevated in synovial fluid of RA patients, reflecting local inflammation.", "protein": "CD93", "relationship_type": "biomarker", "source_pmcid": "PMC12428824" }, { "confidence": "high", "disease": "Cardiovascular disease (atherosclerosis, coronary artery disease)", "glycan_involvement": "O-glycosylation required for stable endothelial CD93 expression and vascular integrity.", "mechanism": "CD93 regulates endothelial function, angiogenesis, and apoptotic cell clearance; gene polymorphisms and protein levels associate with CVD risk.", "protein": "CD93", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12428824" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation affects CD93 stability and function in metabolic regulation.", "mechanism": "Lower sCD93 levels precede diabetes onset; CD93 deficiency impairs glucose clearance and insulin sensitivity in mice.", "protein": "CD93", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Stroke/Ischemia-reperfusion injury", "glycan_involvement": "Glycosylation maintains CD93 function in vascular repair and inflammation modulation.", "mechanism": "CD93 expression increases after cerebral ischemia; knockout mice show worsened inflammation and tissue damage.", "protein": "CD93", "relationship_type": "protective", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Autoimmune encephalomyelitis", "glycan_involvement": "Glycosylation supports CD93-mediated endothelial stability.", "mechanism": "CD93 deficiency leads to increased neuroinflammation and blood-brain barrier disruption.", "protein": "CD93", "relationship_type": "protective", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Glycosylation likely required for CD93\u2019s role in immune cell adhesion and migration.", "mechanism": "CD93 identified as a key gene in periodontitis progression; causal link established via bioinformatics and validation.", "protein": "CD93", "relationship_type": "causal", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Cerebral cavernous malformation", "glycan_involvement": "Glycosylation impacts CD93\u2019s ECM interactions.", "mechanism": "CD93 upregulated in CCM tissue; involved in endothelial activation and ECM remodeling.", "protein": "CD93", "relationship_type": "biomarker", "source_pmcid": "PMC12428824" }, { "confidence": "medium", "disease": "Pneumococcal meningitis", "glycan_involvement": "Glycosylation supports CD93\u2019s cell surface localization and signaling.", "mechanism": "CD93 interacts with integrin \u03b21 to polarize microglia to M1 phenotype, increasing neuroinflammation and damage.", "protein": "CD93", "relationship_type": "causal", "source_pmcid": "PMC12428824" }, { "confidence": "high", "disease": "Feline gingivitis", "glycan_involvement": "Haptoglobin is a glycoprotein; glycosylation is essential for its stability and function as an acute phase reactant.", "mechanism": "Serum haptoglobin is significantly increased in cats with gingivitis, reflecting an acute phase response to local inflammation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Feline gingivitis", "glycan_involvement": "Glycosylation may affect haptoglobin's half-life and immune recognition.", "mechanism": "Serum haptoglobin levels correlate with severity of gingivitis, suggesting utility for disease monitoring.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Chronic gingivostomatitis", "glycan_involvement": "Glycosylation is required for haptoglobin's function and detection.", "mechanism": "Haptoglobin is elevated in chronic gingivostomatitis, with higher levels than in uncomplicated gingivitis.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Feline infectious peritonitis", "glycan_involvement": "Glycosylation supports its acute phase function.", "mechanism": "Haptoglobin is markedly increased during systemic inflammation such as feline infectious peritonitis.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Chronic gingivostomatitis", "glycan_involvement": "Highly glycosylated; glycan structures modulate immunomodulatory properties.", "mechanism": "Serum \u03b11-acid glycoprotein is elevated in cats with chronic gingivostomatitis.", "protein": "\u03b11-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "high", "disease": "Feline gingivitis", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "SAA is not elevated in most cases of feline gingivitis, indicating limited utility as a biomarker for this disease.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Chronic inflammation (general)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "SAA increases in early stages of inflammation and in systemic diseases, but not in mild/localized gingivitis.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation is necessary for function.", "mechanism": "Haptoglobin is increased in periodontal disease in other species, reflecting systemic acute phase response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation modulates anti-inflammatory activity.", "mechanism": "\u03b11-acid glycoprotein is elevated in cats with periodontal disease, indicating systemic inflammation.", "protein": "\u03b11-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12433242" }, { "confidence": "low", "disease": "Feline gingivitis", "glycan_involvement": "Glycosylation may affect assay detection and biological activity.", "mechanism": "Potential for monitoring disease progression and response to therapy.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12433242" }, { "confidence": "high", "disease": "Burkitt lymphoma", "glycan_involvement": "Viral glycoproteins require N-glycosylation for B-cell binding and immune evasion.", "mechanism": "EBV glycoproteins mediate B-cell infection, promoting lymphomagenesis via MYC dysregulation.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350, gp220)", "relationship_type": "causal", "source_pmcid": "PMC12433268" }, { "confidence": "high", "disease": "Burkitt lymphoma", "glycan_involvement": "N-glycosylation modulates CD19 surface expression and BCR signaling.", "mechanism": "CD19 is expressed on BL cells and used for diagnosis.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "high", "disease": "Burkitt lymphoma", "glycan_involvement": "Glycosylation affects antibody binding and immune clearance.", "mechanism": "CD20 is targeted by monoclonal antibodies in BL therapy.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12433268" }, { "confidence": "high", "disease": "Burkitt lymphoma", "glycan_involvement": "N-glycosylation influences CD10 stability and detection.", "mechanism": "CD10 is a diagnostic marker for BL.", "protein": "CD10", "protein_enriched": { "function": "Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhi", "gene_name": "CD72", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX" ], "uniprot_id": "P21854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "N-glycosylation required for BCR assembly and function.", "mechanism": "CD79a is part of the BCR complex, expressed in BL.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "N-glycosylation required for BCR assembly and function.", "mechanism": "CD79b is part of the BCR complex, expressed in BL.", "protein": "CD79b", "protein_enriched": { "function": "Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows ", "gene_name": "DIAPH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "O60610" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "O- and N-glycosylation modulate signaling and cell adhesion.", "mechanism": "CD45 is a pan-leukocyte marker, expressed in BL.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "N-glycosylation affects enzymatic activity and cell interactions.", "mechanism": "CD38 is variably expressed in BL and used for immunophenotyping.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "O-glycosylation creates sialylated epitopes for immune modulation.", "mechanism": "CD43 is expressed in BL and aids in diagnosis.", "protein": "CD43", "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "N- and O-glycosylation regulate ligand binding and migration.", "mechanism": "CD44 is expressed in BL and involved in cell adhesion.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12433268" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "PGP is a heavily N-glycosylated membrane glycoprotein; glycosylation is essential for its proper folding, trafficking, and drug transport function.", "mechanism": "PGP acts as a drug efflux pump, reducing intracellular concentration of chemotherapeutics and conferring multidrug resistance.", "protein": "P-glycoprotein (PGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "GST-\u03c0 is glycosylated; glycosylation may affect stability and cellular localization.", "mechanism": "GST-\u03c0 catalyzes conjugation of glutathione to chemotherapeutic agents, leading to drug detoxification and resistance.", "protein": "Glutathione S-transferase pi (GST-\u03c0)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prost", "gene_name": "GSTP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09211" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "No direct glycosylation involvement reported for p53 in this context.", "mechanism": "High expression/mutation of p53 is associated with poor prognosis, increased lymphatic metastasis, and chemotherapy resistance.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Ki-67 is a glycoprotein; glycosylation may affect nuclear localization and stability.", "mechanism": "Ki-67 is a proliferation marker; elevated levels indicate rapid tumor growth and correlate with poor survival and drug resistance.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Chemotherapy Resistance in Breast Cancer", "glycan_involvement": "N-glycosylation is required for PGP function.", "mechanism": "PGP-mediated drug efflux is a direct cause of chemotherapy resistance.", "protein": "P-glycoprotein (PGP)", "relationship_type": "causal", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Chemotherapy Resistance in Breast Cancer", "glycan_involvement": "Glycosylation may modulate GST-\u03c0 activity.", "mechanism": "GST-\u03c0 detoxifies chemotherapeutic drugs, reducing their efficacy.", "protein": "Glutathione S-transferase pi (GST-\u03c0)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prost", "gene_name": "GSTP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09211" }, "relationship_type": "causal", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Chemotherapy Resistance in Breast Cancer", "glycan_involvement": "Glycosylation may affect Ki-67 function.", "mechanism": "High Ki-67 expression correlates with aggressive tumor phenotype and resistance to chemotherapy.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Chemotherapy Resistance in Breast Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Altered p53 expression/mutation is linked to poor response to chemotherapy.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC12433301" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "N-glycosylation is critical for PGP targeting.", "mechanism": "Targeting PGP may improve chemotherapy efficacy in TNBC.", "protein": "P-glycoprotein (PGP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12433301" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Potential impact of glycosylation on inhibitor design.", "mechanism": "Inhibiting GST-\u03c0 may reduce drug resistance and improve chemotherapy outcomes.", "protein": "Glutathione S-transferase pi (GST-\u03c0)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prost", "gene_name": "GSTP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09211" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12433301" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DAG is a glycoprotein complex; glycosylation is essential for its membrane localization and function.", "mechanism": "Loss or malfunction of DAG due to dystrophin mutations leads to muscle fiber instability and degeneration.", "protein": "Dystrophin-associated glycoprotein complex (DAG)", "relationship_type": "causal", "source_pmcid": "PMC12434798" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Galectin-3 specifically recognizes N-acetyllactosamine motifs on glycoproteins.", "mechanism": "Galectin-3 binds acetyllactosamine-rich N-glycans, mediating cell\u2013cell and cell\u2013matrix interactions important for muscle regeneration.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12434798" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation with acetyllactosamine motifs is upregulated by GlcNAc.", "mechanism": "Increased biosynthesis (via GlcNAc supplementation) enhances muscle regeneration and reduces muscle damage.", "protein": "N-acetyllactosamine-rich N-linked glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12434798" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Enzymatic N-glycosylation branching is critical for glycoprotein function.", "mechanism": "MGATs catalyze N-glycan branching, increasing acetyllactosamine-rich glycoproteins that interact with galectin-3, promoting muscle repair.", "protein": "UDP-N-acetylglucosaminyltransferases (MGATs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12434798" }, { "confidence": "medium", "disease": "Muscle injury/damage", "glycan_involvement": "Binds to N-acetyllactosamine-rich glycoproteins on muscle cells.", "mechanism": "Galectin-3 is upregulated in regenerating muscle and correlates with myogenesis and repair.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12434798" }, { "confidence": "high", "disease": "Muscle injury/damage", "glycan_involvement": "N-glycosylation with acetyllactosamine motifs is protective.", "mechanism": "Enhanced glycosylation reduces histological muscle damage in mdx mice.", "protein": "N-acetyllactosamine-rich N-linked glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12434798" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "N-glycosylation modulates immune responses.", "mechanism": "GlcNAc supplementation increases N-glycan branching, reducing inflammation.", "protein": "N-acetyllactosamine-rich N-linked glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12434798" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation affects CNS repair processes.", "mechanism": "GlcNAc supplementation promotes myelin repair via increased N-glycan branching.", "protein": "N-acetyllactosamine-rich N-linked glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12434798" }, { "confidence": "high", "disease": "Muscle injury/damage", "glycan_involvement": "Not directly glycosylated; used as a marker.", "mechanism": "Elevated serum CPK indicates muscle damage in DMD and injury models.", "protein": "Creatine phosphokinase (CPK)", "relationship_type": "biomarker", "source_pmcid": "PMC12434798" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Binds N-acetyllactosamine-rich glycoproteins in CNS.", "mechanism": "Galectin-3 interaction with N-glycans may promote CNS myelin repair.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12434798" }, { "confidence": "high", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "O-glycosylation pathway enrichment; glycosylation may regulate LRAT function in metastasis.", "mechanism": "Upregulated via lncRNA PCAT1/miR-370-3p axis, promotes OS cell invasion, migration, and proliferation.", "protein": "LRAT", "protein_enriched": { "function": "Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters (PubMed:9920938). Retinyl esters are storage forms of vitamin A (Probabl", "gene_name": "LRAT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95237" }, "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "high", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "O-glycosylation pathway enrichment; MFAP5 is an ECM glycoprotein, glycosylation may affect cell adhesion/migration.", "mechanism": "Upregulated via circ_0012586/miR-200b-5p axis, promotes OS cell invasion, migration, and proliferation.", "protein": "MFAP5", "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "Potential glycoprotein; role in glycosylation not directly shown.", "mechanism": "Most upregulated mRNA in metastatic OS tissues.", "protein": "CFAP47", "protein_enriched": { "function": "Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphat", "gene_name": "MARVELD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N4S9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "FAS is a glycoprotein receptor; glycosylation may affect apoptotic signaling.", "mechanism": "miR-20a modulates FAS expression, affecting OS lung metastasis.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "Potential glycoprotein; glycosylation may regulate stability/function.", "mechanism": "Downregulated by circ100284, promoting OS cell invasion/migration.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "Potential glycoprotein; glycosylation may affect cell adhesion.", "mechanism": "Downregulated by circ100284, promoting OS cell invasion/migration.", "protein": "EMP1", "protein_enriched": { "function": "Mediates selective neuronal growth and axon targeting. Contributes to the guidance of developing axons and remodeling of mature circuits in the limbic system. Essential for normal growth of the hippoc", "gene_name": "LSAMP", "glycan_count": 3, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G80920RR", "G62765YT" ], "uniprot_id": "Q13449" }, "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Osteosarcoma with lung metastasis", "glycan_involvement": "Potential glycoprotein; glycosylation may regulate kinase activity.", "mechanism": "Upregulated via lncRNA DANCR/miR-1972/miR-335-5p axis, promotes proliferation/metastasis.", "protein": "ROCK1", "protein_enriched": { "function": "Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:191316", "gene_name": "ROCK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13464" }, "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "MFAP5 is O-glycosylated; glycosylation may affect ECM interactions.", "mechanism": "MFAP5 promotes cancer progression.", "protein": "MFAP5", "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "MFAP5 is O-glycosylated; glycosylation may affect ECM interactions.", "mechanism": "MFAP5 promotes cancer progression.", "protein": "MFAP5", "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "MFAP5 is O-glycosylated; glycosylation may affect ECM interactions.", "mechanism": "MFAP5 promotes cancer progression.", "protein": "MFAP5", "relationship_type": "causal", "source_pmcid": "PMC12435275" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type 1A)", "glycan_involvement": "Defective N-linked glycosylation of multiple glycoproteins.", "mechanism": "Mutations in PMM2 impair conversion of mannose-6-phosphate to mannose-1-phosphate, disrupting N-glycan precursor synthesis.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Developmental delay", "glycan_involvement": "N-glycosylation required for neuronal function and development.", "mechanism": "Impaired N-glycosylation affects neurodevelopmental processes.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Ocular abnormalities (hypertelorism, strabismus)", "glycan_involvement": "N-glycosylation of proteins involved in eye development.", "mechanism": "Defective glycosylation disrupts development of ocular structures.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Muscular hypotonia/weakness", "glycan_involvement": "N-glycosylation of muscle glycoproteins.", "mechanism": "Glycosylation defects impair muscle protein function.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "N-glycosylation and fucosylated glycans essential for learning and memory.", "mechanism": "Disrupted glycosylation affects cognitive processes and brain function.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "medium", "disease": "Cardiovascular involvement (pericarditis, pericardial effusion)", "glycan_involvement": "N-glycosylation of cardiac proteins.", "mechanism": "Glycosylation defects affect cardiac glycoproteins and tissue integrity.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Clotting disorder (antithrombin III deficiency)", "glycan_involvement": "N-glycosylation required for antithrombin III function.", "mechanism": "Defective glycosylation reduces antithrombin III activity.", "protein": "Antithrombin III", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "medium", "disease": "Hepatic involvement (elevated transaminases)", "glycan_involvement": "N-glycosylation of hepatic proteins.", "mechanism": "Glycosylation defects impair liver glycoprotein function.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type 1A)", "glycan_involvement": "Essential for N-glycan biosynthesis.", "mechanism": "Reduced GDP-mannose synthesis limits glycan precursor availability.", "protein": "GDP-mannose", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "PMM2-CDG (Congenital Disorder of Glycosylation type 1A)", "glycan_involvement": "Required for N-glycosylation pathway.", "mechanism": "Deficiency impairs transfer of mannose residues to glycoproteins.", "protein": "Dolichol-phosphate-mannose", "relationship_type": "causal", "source_pmcid": "PMC12435617" }, { "confidence": "high", "disease": "Acute Dengue infection", "glycan_involvement": "Desialylation of GPIb exposes underlying glycan structures, promoting clearance.", "mechanism": "Altered glycosylation of GPIb enhances platelet recognition and phagocytosis by macrophages during Dengue infection.", "protein": "Platelet glycoprotein Ib (GPIb)", "relationship_type": "causal", "source_pmcid": "PMC12436210" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Altered N-glycosylation reduces platelet lifespan.", "mechanism": "Glycan modifications on GPIIb/IIIa affect platelet aggregation and survival, contributing to thrombocytopenia in Dengue.", "protein": "Platelet glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12436210" }, { "confidence": "medium", "disease": "Acute Dengue infection", "glycan_involvement": "O-glycosylation modulates P-selectin-mediated adhesion.", "mechanism": "Upregulation and glycosylation changes of P-selectin reflect platelet activation in Dengue.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12436210" }, { "confidence": "high", "disease": "Soft Tissue Sarcoma", "glycan_involvement": "Catalyzes N-glycosylation of nascent proteins, affecting protein folding and immune evasion.", "mechanism": "Promotes proliferation and migration of STS cells; silencing inhibits tumor growth.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12436507" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation of CD63 alters cell surface localization and function.", "mechanism": "Mediates glycosylation of CD63, influencing drug resistance and invasiveness.", "protein": "RPN2", "protein_enriched": { "function": "Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to a", "gene_name": "RPN1", "glycan_count": 23, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G11314AS", "G35029YA", "G37399XV", "G41247ZX", "G47644PP", "G50282JC", "G60033FS", "G90659AW", "G92406TI", "G05049YU", "G05724UK", "G31852PQ", "G39188ZX", "G40926MX", "G46687AB", "G48584BU", "G55220VL", "G70101JE", "G72747WU", "G80966KZ", "G70994MS" ], "uniprot_id": "P04843" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12436507" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation", "glycan_involvement": "Defective glucosyltransferase activity in N-glycan precursor synthesis.", "mechanism": "Mutations impair N-glycosylation, leading to multisystem dysfunction.", "protein": "ALG6", "protein_enriched": { "function": "Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)", "gene_name": "ALG6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9Y672" }, "relationship_type": "causal", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "N-glycosylation of immune regulators (e.g., MITA/STING) modulates immune response.", "mechanism": "High expression correlates with poor prognosis and immune infiltration.", "protein": "DDOST", "protein_enriched": { "function": "Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to a", "gene_name": "DDOST", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P39656" }, "relationship_type": "biomarker", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Soft Tissue Sarcoma", "glycan_involvement": "O-glycosylation of Notch receptor regulates ligand binding and signaling.", "mechanism": "Modulates Notch signaling, influencing immune cell infiltration and prognosis.", "protein": "MFNG", "protein_enriched": { "function": "May be required for replication-independent chromatin assembly. May serve as a negative regulator of T-cell receptor (TCR) signaling via inhibition of calcineurin. Inhibition of activated calcineurin ", "gene_name": "CABIN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Liver Cancer", "glycan_involvement": "Initiates glycosaminoglycan synthesis in proteoglycans, affecting tumor-stroma interactions.", "mechanism": "Elevated expression associated with poor prognosis; impacts matrix composition.", "protein": "XYLT2", "protein_enriched": { "function": "Plays a role as a transcription factor (PubMed:22132193, PubMed:25355627). Mediates positive transcriptional regulation of several chaperone genes during the heat shock response in a HSF1-dependent ma", "gene_name": "IER5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5VY09" }, "relationship_type": "biomarker", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Catalyzes linker region assembly in proteoglycans, influencing ECM structure.", "mechanism": "High expression linked to poor prognosis.", "protein": "B3GAT3", "protein_enriched": { "function": "Glycosaminoglycans biosynthesis (PubMed:25893793). Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridi", "gene_name": "B3GAT3", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "O94766" }, "relationship_type": "biomarker", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Lung Adenocarcinoma", "glycan_involvement": "Galactosylation of N- and O-glycans modulates immune microenvironment.", "mechanism": "Regulates immune exclusion and CD8+ T cell infiltration; affects PD-1/PD-L1 pathway.", "protein": "B4GALT2", "protein_enriched": { "function": "Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts", "gene_name": "B4GALT7", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBV7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "N-glycosylation of CD133 supports stem cell maintenance and Wnt/\u03b2-catenin signaling.", "mechanism": "Promotes tumor progression by stabilizing CD133 via N-glycosylation.", "protein": "GLT8D1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12436507" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "GPI-anchor biosynthesis affects cell surface protein localization.", "mechanism": "Overexpression enhances proliferation and migration; linked to poor survival.", "protein": "PIGC", "protein_enriched": { "function": "Catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol", "gene_name": "PIGL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2B2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12436507" }, { "confidence": "high", "disease": "Major Depression (MD)", "glycan_involvement": "CRP is a glycoprotein; its glycosylation is essential for stability and function.", "mechanism": "CRP levels are elevated in MD, reflecting systemic inflammation and innate immune activation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12436863" }, { "confidence": "high", "disease": "First-Episode Major Depression (FEMD)", "glycan_involvement": "Glycosylation of CRP is required for its secretion and immune recognition.", "mechanism": "CRP is significantly elevated in FEMD, indicating acute inflammatory response.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12436863" }, { "confidence": "high", "disease": "Recurrent Major Depression (RMD)", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells.", "mechanism": "CRP is elevated in RMD, suggesting ongoing inflammation in chronic depression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12436863" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation affects CRP's immune effector functions.", "mechanism": "CRP is elevated in schizophrenia, with larger effect sizes than in MD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12436863" }, { "confidence": "medium", "disease": "Opioid Use Disorder", "glycan_involvement": "No direct glycosylation involvement described in this article.", "mechanism": "Naltrexone acts as an opioid receptor antagonist to reduce opioid cravings and prevent relapse.", "protein": "Naltrexone", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12438203" }, { "confidence": "medium", "disease": "Opioid Use Disorder", "glycan_involvement": "No direct glycosylation involvement described in this article.", "mechanism": "Buprenorphine acts as a partial opioid agonist to reduce withdrawal symptoms and cravings.", "protein": "Buprenorphine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12438203" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "Glycosylation is essential for P-glycoprotein folding, trafficking, and drug transport activity.", "mechanism": "P-glycoprotein influences methadone absorption and plasma concentration, affecting efficacy and safety of opioid substitution therapy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12438269" }, { "confidence": "medium", "disease": "Torsades de Pointes", "glycan_involvement": "Glycosylation affects P-glycoprotein localization and function in cardiac tissue.", "mechanism": "Proper P-glycoprotein function may reduce cardiac side effects (QTc prolongation) by modulating methadone bioavailability.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "protective", "source_pmcid": "PMC12438269" }, { "confidence": "high", "disease": "Immuno-metabolic depression", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and immune function.", "mechanism": "Elevated CRP reflects systemic low-grade inflammation associated with atypical depressive symptoms.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "high", "disease": "Immuno-metabolic depression", "glycan_involvement": "Composite marker of several N-glycosylated acute-phase proteins; glycosylation modulates their inflammatory properties.", "mechanism": "Elevated glycoprotein acetyls indicate chronic inflammation in a depression subtype.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Immuno-metabolic depression", "glycan_involvement": "Leptin is glycosylated, which affects its secretion and receptor binding.", "mechanism": "Leptin resistance is associated with metabolic abnormalities and depressive symptoms.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Cardiometabolic diseases", "glycan_involvement": "Glycosylation of acute-phase proteins modulates their inflammatory activity.", "mechanism": "Elevated glycoprotein acetyls predict increased risk for cardiometabolic diseases in depressed individuals.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Cardiometabolic diseases", "glycan_involvement": "N-glycosylation influences CRP's role in inflammation.", "mechanism": "High CRP levels are linked to increased cardiometabolic risk in depression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects leptin's bioactivity.", "mechanism": "Leptin resistance is a hallmark of obesity and is linked to depressive symptoms.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates leptin's receptor interactions.", "mechanism": "Leptin resistance co-occurs with insulin resistance in immuno-metabolic depression.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Reflects altered glycosylation of acute-phase proteins.", "mechanism": "Elevated levels distinguish a subtype of depression with inflammatory and metabolic features.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "N-glycosylation affects CRP's inflammatory signaling.", "mechanism": "High CRP is associated with depressive symptoms, especially in the immuno-metabolic subtype.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation of acute-phase proteins is altered in obesity.", "mechanism": "Elevated glycoprotein acetyls are linked to obesity in depressed individuals.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12438868" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "O-glycosylation, especially \u03b1-1,4-GlcNAc, mediates antibacterial effect and risk modulation.", "mechanism": "Loss or downregulation of MUC6 increases risk and correlates with poor prognosis; shorter VNTR alleles reduce antibacterial glycan (\u03b1-1,4-GlcNAc) and promote H. pylori infection.", "protein": "MUC6", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation; altered glycoforms in serrated pathway lesions.", "mechanism": "Ectopic MUC6 expression in colorectal tumors and polyps correlates with improved prognosis; genetic polymorphisms (shorter alleles) increase susceptibility.", "protein": "MUC6", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12440278" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "O-glycosylation; loss leads to enrichment of mannose-rich glycans and tumor-promoting MAPK signaling.", "mechanism": "MUC6 inhibits tumor growth and invasion; regulated by lncRNA CASC2/miR-24 and PDX1; loss of MUC6 during progression to invasive carcinoma.", "protein": "MUC6", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12440278" }, { "confidence": "medium", "disease": "Cholangiocarcinoma", "glycan_involvement": "O-glycosylation; TFF2 cross-links via GlcNAc-specific interaction.", "mechanism": "MUC6 expression (with TFF2) increases mucin viscosity, reducing lymph node metastasis; downregulation necessary for metastasis.", "protein": "MUC6", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "O-glycosylation; mucin viscosity and barrier function.", "mechanism": "Upregulation in well-differentiated tumors predicts improved prognosis; loss correlates with dedifferentiation and metastasis.", "protein": "MUC6", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12440278" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation; preferential formation of Tn antigen via ppGalNAc-Ts.", "mechanism": "MUC6-Tn glycoform is enriched in breast cancer cells, serving as a substrate for tumor antigen and vaccine development.", "protein": "MUC6", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "O-glycosylation; glycoform alterations in tumor tissue.", "mechanism": "Subtype-specific MUC6 expression aids differential diagnosis and is associated with favorable prognosis in mucinous adenocarcinoma.", "protein": "MUC6", "relationship_type": "biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "O-glycosylation; tissue-specific expression.", "mechanism": "MUC6 expression in seminal vesicle/ejaculatory duct tissue distinguishes prostate cancer from benign tissue, reducing biopsy false positives.", "protein": "MUC6", "relationship_type": "biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "high", "disease": "Endometrial cancer (GAS subtype)", "glycan_involvement": "O-glycosylation; IHC marker for differentiation.", "mechanism": "Focal MUC6 expression (with HIK1083) provides high specificity for diagnosis of gastric-type adenocarcinoma.", "protein": "MUC6", "relationship_type": "biomarker", "source_pmcid": "PMC12440278" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "O-glycosylation; immune phenotype modulation.", "mechanism": "Upregulation after radiation exposure alters mucosal immunity, resembling IBD pathogenesis; IHC identifies gastric-type metaplasia.", "protein": "MUC6", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12440278" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "VWF is a heavily glycosylated protein; glycosylation affects its multimerization and function in vascular integrity.", "mechanism": "Lower plasma VWF levels are associated with faster cognitive decline and increased neurodegeneration in regions affected by AD.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation is essential for VWF secretion and stability in plasma.", "mechanism": "Lower plasma VWF levels predict steeper longitudinal decline in MMSE and CDR-SB scores.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "high", "disease": "Brain atrophy", "glycan_involvement": "Glycosylation modulates VWF's interaction with endothelial cells and its clearance.", "mechanism": "Lower plasma VWF levels are associated with faster reduction in hippocampal, entorhinal cortex, and fusiform gyrus volumes, and faster ventricular enlargement.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation influences VWF multimer size and pro-thrombotic activity.", "mechanism": "Previous meta-analyses suggest higher VWF levels may be linked to increased risk of vascular dementia, but results are inconsistent.", "protein": "von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation not directly implicated in this relationship.", "mechanism": "No significant association between plasma VWF levels and CSF AD biomarkers (A\u03b242, total tau, p-tau181), suggesting non-amyloid/tau pathway involvement.", "protein": "von Willebrand Factor", "relationship_type": "non-causal", "source_pmcid": "PMC12440976" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "ADAMTS13 is glycosylated, affecting its secretion and proteolytic activity.", "mechanism": "Elevated ADAMTS13 activity (which cleaves VWF) is associated with increased diabetes risk.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates ADAMTS13 stability and function.", "mechanism": "Low ADAMTS13 activity is associated with increased risk of dementia.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12440976" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation is required for VWF's normal function in vascular homeostasis.", "mechanism": "Higher plasma VWF levels may be protective against rapid cognitive decline in older adults without dementia.", "protein": "von Willebrand Factor", "relationship_type": "protective", "source_pmcid": "PMC12440976" }, { "confidence": "medium", "disease": "Brain atrophy", "glycan_involvement": "Glycosylation affects VWF's interaction with extracellular matrix and endothelial cells.", "mechanism": "Higher plasma VWF levels may slow region-specific brain atrophy.", "protein": "von Willebrand Factor", "relationship_type": "protective", "source_pmcid": "PMC12440976" }, { "confidence": "low", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation regulates VWF's pro-thrombotic activity.", "mechanism": "Higher VWF levels may contribute to vascular pathology, increasing risk for vascular dementia (prior studies, not confirmed in current cohort).", "protein": "von Willebrand Factor", "relationship_type": "causal (suggested)", "source_pmcid": "PMC12440976" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Mucin-type O-glycosylation critical for antigenicity and detection.", "mechanism": "CA-125 is released by mesothelial cells and tumor cells; elevated levels reflect tumor burden/progression.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "O-glycosylation confers antigenic properties recognized by clinical assays.", "mechanism": "CA-125 is used to monitor disease progression and response to therapy in ovarian cancer.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation enables secretion from mesothelial cells in response to mechanical stress.", "mechanism": "CA-125 correlates with increased intracardiac filling pressures and right-sided heart dysfunction.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "medium", "disease": "Pulmonary hypertension", "glycan_involvement": "Glycosylation facilitates release from mesothelial cells under pressure.", "mechanism": "Elevated CA-125 reflects right-sided cardiac overload and pulmonary hypertension.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "medium", "disease": "Right ventricular dysfunction", "glycan_involvement": "O-glycosylation required for secretion and detection.", "mechanism": "CA-125 levels may outperform natriuretic peptides in detecting right-sided dysfunction.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "medium", "disease": "Ascites", "glycan_involvement": "Glycosylation supports antigen stability in peritoneal fluid.", "mechanism": "CA-125 is elevated in ascites due to mesothelial cell activation from peritoneal fluid accumulation.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation is essential for immunodetection; cross-reactivity possible.", "mechanism": "CA-125 levels may be falsely elevated due to HF, complicating cancer monitoring.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation enables dynamic secretion in response to fluid overload.", "mechanism": "CA-125 normalization after diuresis indicates its utility in HF management.", "protein": "Carbohydrate antigen-125 (CA-125)", "relationship_type": "biomarker", "source_pmcid": "PMC12441411" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is a glycoprotein; glycosylation affects stability and shedding.", "mechanism": "H157Y variant increases TREM2 shedding, reduces cell surface TREM2, increases AD risk and accelerates progression, especially with APOE \u03b54.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12441928" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Secreted glycoprotein; glycosylation required for secretion and function.", "mechanism": "Upregulated in TREM2 H157Y carriers with AD, reflecting increased neuroinflammation.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect secretion and ECM interactions.", "mechanism": "Upregulated in TREM2 H157Y carriers; associated with neurodegeneration and cerebrovascular changes.", "protein": "SMOC1", "protein_enriched": { "function": "Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation", "gene_name": "SMOC1", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT", "G57321FI", "G43417UB", "G53434XO", "G00912UN", "G02815KT", "G27058EU", "G61256FT", "G76295SF" ], "uniprot_id": "Q9H4F8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates ligand binding and trafficking.", "mechanism": "Downregulated in TREM2 H157Y carriers; LRP1 mediates amyloid clearance.", "protein": "LRP1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Peripheral immune dysregulation", "glycan_involvement": "Glycosylation critical for lysosomal targeting and function.", "mechanism": "Upregulated in TREM2 H157Y carriers; involved in immune cell activation.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Binds sialylated glycans; glycosylation essential for ligand recognition.", "mechanism": "Altered in TREM2 H157Y carriers; modulates immune cell signaling and inflammation.", "protein": "SIGLEC10", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid (By similarity). The sialic acid recognition site ma", "gene_name": "SIGLEC10", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G31852PQ", "G41247ZX", "G59626AS", "G80920RR" ], "uniprot_id": "Q96LC7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Altered in TREM2 H157Y carriers; binds TREM2, modulates complement-mediated synapse removal.", "protein": "C1QA", "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Peripheral immune dysregulation", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Upregulated in TREM2 H157Y carriers; involved in NK and T cell activation.", "protein": "CD244", "protein_enriched": { "function": "Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the act", "gene_name": "CD244", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q9BZW8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "medium", "disease": "Vascular dysfunction", "glycan_involvement": "Glycosylation may affect TREM2 interactions with vascular ligands.", "mechanism": "H157Y variant alters vascular-related proteins (e.g., VEGF receptors), affecting angiogenesis.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "low", "disease": "Bone/ossification disorders", "glycan_involvement": "Glycosylation may modulate TREM2 signaling in bone cells.", "mechanism": "H157Y variant upregulates ossification-related proteins, suggesting altered bone metabolism.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12441928" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "MOG-reactive CD8+ T cells trigger EAE and demyelination via recognition of MOG neoantigens.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12442617" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Not directly specified, but vimentin is glycosylated; citrullination alters antigenicity.", "mechanism": "Citrullinated vimentin peptides act as neoantigens, triggering autoantibody and T cell responses.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12442617" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Fibrinogen is glycosylated; citrullination modifies antigenic epitopes.", "mechanism": "Citrullinated fibrinogen peptides are recognized by ACPAs and autoreactive T cells.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12442617" }, { "confidence": "high", "disease": "Ankylosing spondylitis (AS)", "glycan_involvement": "ITGA2B is glycosylated; carboxyethylation is a PTM affecting immune recognition.", "mechanism": "Carboxyethylation of ITGA2B at Cys96 generates neoantigen presented by HLA-DRB1*04, triggering T/B cell responses.", "protein": "ITGA2B (Integrin alpha-IIb)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12442617" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAc is a glycosylation PTM directly involved in antigenicity.", "mechanism": "O-GlcNAcylated peptides presented by HLA-B*07 elicit cytotoxic T cell responses in leukemia.", "protein": "O-GlcNAc-modified peptides", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12442617" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Histones can be O-GlcNAcylated; acetylation is the main PTM discussed.", "mechanism": "Acetylated histones act as neoantigens, correlating with disease activity and autoantibody production.", "protein": "Histones", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12442617" }, { "confidence": "medium", "disease": "Inflammatory diseases (general)", "glycan_involvement": "Not specified; redox PTM is main focus.", "mechanism": "S-glutathionylation enhances nuclear translocation, activating PPAR\u03b2/\u03b4 and inhibiting macrophage inflammation.", "protein": "Fatty acid-binding protein 5", "relationship_type": "protective", "source_pmcid": "PMC12442617" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "GAPDH is glycosylated; succination is the relevant PTM.", "mechanism": "Succination by DMF at Cys152 downregulates glycolysis, contributing to anti-inflammatory effects in MS.", "protein": "GAPDH", "protein_enriched": { "function": "Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde", "gene_name": "GAPDH", "glycan_count": 20, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G05528SJ", "G06356OH", "G11629QQ", "G14547CB", "G20706XG", "G27058EU", "G48414YA", "G56784JY", "G57888GL", "G63136LV", "G65344XH", "G68490OW", "G78787DI", "G90787TS", "G49108TO", "G22310AV", "G43669FQ", "G84452RH", "G70994MS" ], "uniprot_id": "P04406" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12442617" }, { "confidence": "medium", "disease": "Psoriasis/Atopic dermatitis", "glycan_involvement": "CD1a is glycosylated; lipid presentation is main mechanism.", "mechanism": "CD1a presents lipid neoantigens to autoreactive T cells; sphingomyelin can block TCR recognition.", "protein": "CD1a", "protein_enriched": { "function": "Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells", "gene_name": "CD1D", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P15813" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12442617" }, { "confidence": "high", "disease": "Autoimmune diseases (general)", "glycan_involvement": "HLA molecules are glycosylated; glycosylation may affect peptide binding and presentation.", "mechanism": "Disease-associated HLA alleles present PTM-derived neoantigens, driving autoreactive T cell expansion.", "protein": "HLA class I/II molecules", "relationship_type": "causal", "source_pmcid": "PMC12442617" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2-MD)", "glycan_involvement": "Laminin \u03b12 is a glycoprotein; glycosylation is essential for its structure and function.", "mechanism": "Loss-of-function mutations in LAMA2 cause deficiency of laminin \u03b12, disrupting muscle basement membrane integrity and leading to muscular dystrophy.", "protein": "Laminin \u03b12 (LAMA2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "high", "disease": "LAMA2-related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "LM-211 is a glycoprotein complex; glycosylation affects receptor binding.", "mechanism": "Deficiency of LM-211 (\u03b12\u03b21\u03b31) impairs muscle fiber stability and regeneration.", "protein": "Laminin-211 (LM-211)", "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "high", "disease": "Blood-brain barrier disruption", "glycan_involvement": "Glycosylation of laminin \u03b12 is required for proper assembly of the basal lamina.", "mechanism": "Laminin \u03b12 loss in vascular and leptomeningeal fibroblasts and astrocytes disrupts gliovascular basal lamina, impairing BBB integrity.", "protein": "Laminin \u03b12 (LAMA2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "Brain white matter abnormalities", "glycan_involvement": "Glycosylation may affect laminin interactions with myelin proteins.", "mechanism": "Deficiency leads to downregulation of myelin-related genes and impaired myelin sheath formation.", "protein": "Laminin \u03b12 (LAMA2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "Occipital pachygyria", "glycan_involvement": "Proper glycosylation is required for laminin-mediated cell adhesion.", "mechanism": "Impaired gliovascular basal lamina affects neuronal migration, leading to cortical malformations.", "protein": "Laminin \u03b12 (LAMA2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2-MD)", "glycan_involvement": "\u03b1-dystroglycan is heavily O-glycosylated; glycosylation is critical for laminin binding.", "mechanism": "Acts as a receptor for LM-211; disruption of this interaction contributes to muscle pathology.", "protein": "\u03b1-dystroglycan (Dag1)", "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "LAMA2-related muscular dystrophy (LAMA2-MD)", "glycan_involvement": "Integrins are glycoproteins; glycosylation modulates ligand binding.", "mechanism": "Integrins are upregulated in Lama2-deficient muscle, possibly as compensation for loss of LM-211 signaling.", "protein": "Integrins (e.g., Itgb2, Itgb7)", "relationship_type": "causal", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "LAMA2-related muscular dystrophy (LAMA2-MD)", "glycan_involvement": "Laminin \u03b11 is a glycoprotein; glycosylation affects function.", "mechanism": "Upregulated in Lama2-deficient muscle and brain, possibly compensating for loss of laminin \u03b12.", "protein": "Laminin \u03b11 (LAMA1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "compensatory", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Collagen VI is glycosylated; glycosylation affects matrix assembly.", "mechanism": "Upregulated in Lama2-deficient muscle, contributing to extracellular matrix expansion and fibrosis.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "biomarker", "source_pmcid": "PMC12443477" }, { "confidence": "medium", "disease": "Muscle regeneration defects", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation modulates cell adhesion.", "mechanism": "Upregulated in dystrophic muscle, associated with impaired regeneration and fibrosis.", "protein": "Fibronectin (Fn1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12443477" }, { "confidence": "high", "disease": "Hashimoto\u2019s thyroiditis (HT)", "glycan_involvement": "N-glycosylation (complex-type) of Fas modulates Fas/FasL signaling and apoptosis sensitivity.", "mechanism": "Fas-mediated apoptosis eliminates thyrocytes, contributing to thyroid destruction in HT.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "Thyroid destruction", "glycan_involvement": "Complex-type N-glycans on Fas are required for efficient apoptosis signaling.", "mechanism": "Upregulated Fas on thyrocytes leads to apoptosis and tissue destruction.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "medium", "disease": "Autoimmunity", "glycan_involvement": "Altered N-glycosylation may dysregulate Fas signaling.", "mechanism": "Loss of immunotolerance via Fas-mediated apoptosis promotes autoimmunity.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "Hashimoto\u2019s thyroiditis (HT)", "glycan_involvement": "Inhibition of complex-type N-glycans (by swainsonine) protects thyrocytes from Fas-induced apoptosis.", "mechanism": "Modulating Fas glycosylation (e.g., with swainsonine) can reduce thyrocyte apoptosis.", "protein": "Fas (CD95)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12445433" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "\u03b12,6-sialylation of Fas N-glycans reduces FasL-induced signaling.", "mechanism": "ST6Gal I-mediated sialylation of Fas inhibits receptor oligomerization and apoptosis.", "protein": "ST6Gal I", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Sialylation and complex-type N-glycans modulate Fas signaling.", "mechanism": "Altered Fas glycosylation can affect apoptosis resistance in cancer cells.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "Hashimoto\u2019s thyroiditis (HT)", "glycan_involvement": "Upregulation of complex-type and sialylated N-glycans on Fas in apoptotic thyrocytes.", "mechanism": "Increased Fas expression and altered glycosylation are associated with HT.", "protein": "Fas (CD95)", "relationship_type": "biomarker", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "Thyroid destruction", "glycan_involvement": "Blocking complex-type N-glycans prevents efficient Fas/FasL signaling.", "mechanism": "Swainsonine-mediated inhibition of complex-type N-glycans reduces apoptosis and protects thyrocytes.", "protein": "Fas (CD95)", "relationship_type": "protective", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "Hashimoto\u2019s thyroiditis (HT)", "glycan_involvement": "Prevents formation of complex-type N-glycans, reducing apoptosis.", "mechanism": "Swainsonine treatment decreases caspase activity and nuclear fragmentation in thyrocytes.", "protein": "Fas (CD95)", "relationship_type": "protective", "source_pmcid": "PMC12445433" }, { "confidence": "medium", "disease": "Hashimoto\u2019s thyroiditis (HT)", "glycan_involvement": "Inflammation-induced changes in N-glycosylation enhance Fas-mediated cell death.", "mechanism": "Proinflammatory cytokines (e.g., IFN\u03b3) upregulate Fas and alter glycosylation, increasing apoptosis.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12445433" }, { "confidence": "high", "disease": "White matter brain ageing", "glycan_involvement": "Altered N-glycosylation increases pro-inflammatory activity.", "mechanism": "Elevated AGP reflects systemic inflammaging linked to white matter changes.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. 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"G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446222" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation modulates complement activation.", "mechanism": "C3 activation contributes to demyelination.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446222" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "O-glycosylation affects receptor binding.", "mechanism": "ApoE glycoforms influence lipid transport and vascular health.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12446222" }, { "confidence": "high", "disease": "Chronic heart failure (CHF)", "glycan_involvement": "BNP is glycosylated, affecting its stability and detection.", "mechanism": "BNP is released in response to ventricular stretch and volume overload, reflecting heart failure severity.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "Chronic heart failure (CHF)", "glycan_involvement": "NT-proBNP is glycosylated, influencing its plasma half-life and immunoassay detection.", "mechanism": "NT-proBNP levels correlate with heart failure severity and prognosis.", "protein": "N-terminal pro-brain natriuretic peptide (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "Albumin glycosylation status may affect its function and clearance.", "mechanism": "Low albumin/globulin ratio indicates malnutrition/inflammation, predicting poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "Globulins are glycosylated, modulating immune response and inflammation.", "mechanism": "High globulin (low albumin/globulin ratio) reflects inflammation, associated with worse outcomes.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "Cholinesterase is glycosylated, which may affect its serum levels and activity.", "mechanism": "Low cholinesterase levels predict increased mortality and readmission risk.", "protein": "Cholinesterase", "protein_enriched": { "function": "Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters", "gene_name": "BCHE", "glycan_count": 40, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G00912UN", "G01650EU", "G11314AS", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G37881RL", "G40574BA", "G41247ZX", "G59626AS", "G62765YT", "G80920RR", "G83646BJ", "G86795LJ", "G95865ZB", "G43089EG", "G70441OD", "G08918WF", "G27058EU", "G43223CG", "G11629QQ", "G12270AG", "G13694XX", "G15169WU", "G48414YA", "G55412XP", "G62461SM", "G81263BG", "G84452RH", "G28465XX", "G06247RL", "G27947YN", "G42466VF", "G45395BF", "G70232NH", "G70619PT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P06276" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "medium", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "Alkaline phosphatase glycosylation affects its stability and activity.", "mechanism": "Elevated levels reflect liver congestion/damage, associated with poor prognosis.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "medium", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "CRP is glycosylated, which modulates its immune functions.", "mechanism": "Elevated hsCRP indicates systemic inflammation, predicting adverse outcomes.", "protein": "Hypersensitive C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "medium", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "D-dimer is derived from glycosylated fibrin; glycan status affects degradation and detection.", "mechanism": "Elevated D-dimer reflects coagulation activation, associated with increased mortality.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "medium", "disease": "All-cause mortality in elderly CHF", "glycan_involvement": "Basophil granule proteins are glycosylated, influencing immune signaling.", "mechanism": "Basophil count is predictive of mortality; granule proteins may modulate inflammation.", "protein": "Basophil granule proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "Glycosylation of both proteins affects ratio and functional impact.", "mechanism": "Low ratio predicts cardiac events and rehospitalization.", "protein": "Albumin/globulin ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12446311" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation is required for its stability and secretion.", "mechanism": "Low serum ceruloplasmin is a diagnostic marker for Wilson disease due to impaired copper incorporation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation is essential for ceruloplasmin function; altered glycosylation may affect its activity.", "mechanism": "Defective ATP7B impairs copper incorporation into ceruloplasmin, leading to low levels and copper accumulation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "causal", "source_pmcid": "PMC12446559" }, { "confidence": "medium", "disease": "Congenital disorder of glycosylation", "glycan_involvement": "Defective glycosylation directly reduces ceruloplasmin levels.", "mechanism": "Low ceruloplasmin observed in a patient with congenital disorder of glycosylation, mimicking Wilson disease biochemistry.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "Proper glycosylation is required for ceruloplasmin therapeutic efficacy.", "mechanism": "Restoring ceruloplasmin levels or function may help normalize copper metabolism.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation affects ceruloplasmin stability and measurement accuracy.", "mechanism": "Non-ceruloplasmin-bound copper (NCC) is elevated in Wilson disease; calculated using ceruloplasmin levels.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation status may influence ceruloplasmin quantification and REC calculation.", "mechanism": "Relative exchangeable copper (REC), calculated using ceruloplasmin and total copper, is a highly specific and sensitive biomarker for Wilson disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation impacts ceruloplasmin's copper-binding capacity.", "mechanism": "Exchangeable copper (CuEXC) is increased in Wilson disease due to low ceruloplasmin and copper overload.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation is required for ceruloplasmin secretion and function.", "mechanism": "Low ceruloplasmin and high REC distinguish Wilson disease from healthy carriers and controls.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation affects ceruloplasmin's diagnostic reliability.", "mechanism": "Ceruloplasmin levels are used in the Leipzig score for Wilson disease diagnosis.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12446559" }, { "confidence": "medium", "disease": "Congenital disorder of glycosylation", "glycan_involvement": "Direct impact of glycosylation defect on ceruloplasmin levels.", "mechanism": "Defective glycosylation leads to low ceruloplasmin, mimicking Wilson disease biochemistry.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "causal", "source_pmcid": "PMC12446559" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Palmitoylation (lipid modification) at Cys836 regulates ER retention and assembly; not classical glycosylation.", "mechanism": "Reduced palmitoylation of GluA2 impairs AMPAR assembly and synaptic plasticity, contributing to AD pathology.", "protein": "GluA2 (GRIA2)", "relationship_type": "causal", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Facilitates palmitoylation of GluA2 (not classical glycosylation).", "mechanism": "SELENOK promotes GluA2 palmitoylation via DHHC6, supporting AMPAR assembly and synaptic function; its deficiency exacerbates AD.", "protein": "SELENOK", "protein_enriched": { "function": "Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer (PubMed:30361506). Controls the phagocyte respiratory burst and is essentia", "gene_name": "CYBC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BQA9" }, "relationship_type": "protective", "source_pmcid": "PMC12446660" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Catalyzes palmitoylation (lipidation) of GluA2.", "mechanism": "DHHC6 catalyzes GluA2 palmitoylation; impaired DHHC6 activity reduces GluA2 palmitoylation in AD.", "protein": "DHHC6", "protein_enriched": { "function": "Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:15489887, PubMed:15603740, PubMed:24705354, Pub", "gene_name": "ZDHHC17", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IUH5" }, "relationship_type": "causal", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Palmitoylation at Cys836 is critical for ER retention and AMPAR assembly.", "mechanism": "Loss of GluA2 palmitoylation precedes synapse loss and leads to cognitive and synaptic deficits.", "protein": "GluA2 (GRIA2)", "relationship_type": "causal", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Regulates palmitoylation of GluA2.", "mechanism": "SELENOK deficiency leads to early cognitive and synaptic impairments by reducing GluA2 palmitoylation.", "protein": "SELENOK", "protein_enriched": { "function": "Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer (PubMed:30361506). Controls the phagocyte respiratory burst and is essentia", "gene_name": "CYBC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BQA9" }, "relationship_type": "protective", "source_pmcid": "PMC12446660" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Palmitoylation (not classical glycosylation) affects subunit interaction.", "mechanism": "Reduced GluA1\u2013GluA2 interaction/colocalization in AD reflects impaired AMPAR assembly.", "protein": "GluA1 (GRIA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Palmitoylation at Cys836 is the actionable modification.", "mechanism": "Restoring GluA2 palmitoylation via SELENOK overexpression improves cognition and synaptic plasticity in AD models.", "protein": "GluA2 (GRIA2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Acts via palmitoylation pathway.", "mechanism": "Neuronal SELENOK overexpression restores GluA2 palmitoylation, AMPAR assembly, and cognitive function in AD mice.", "protein": "SELENOK", "protein_enriched": { "function": "Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer (PubMed:30361506). Controls the phagocyte respiratory burst and is essentia", "gene_name": "CYBC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BQA9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Palmitoylation status as a biomarker.", "mechanism": "Reduced GluA2 palmitoylation in postmortem AD brains correlates with disease state.", "protein": "GluA2 (GRIA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12446660" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Palmitoylation of GluA2.", "mechanism": "DHHC6 deficiency reduces GluA2 palmitoylation, impairing AMPAR assembly and synaptic function.", "protein": "DHHC6", "protein_enriched": { "function": "Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:15489887, PubMed:15603740, PubMed:24705354, Pub", "gene_name": "ZDHHC17", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IUH5" }, "relationship_type": "causal", "source_pmcid": "PMC12446660" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation required for membrane localization and barrier function.", "mechanism": "Downregulation leads to increased gut permeability and LPS translocation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "high", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation stabilizes protein-protein interactions at junctions.", "mechanism": "Loss/disruption of ZO-1 impairs tight junctions, promoting endotoxemia.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "medium", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation modulates barrier selectivity.", "mechanism": "Reduced expression increases paracellular permeability.", "protein": "Claudin-4", "protein_enriched": { "function": "Can associate with other claudins to regulate tight junction structural and functional strand dynamics (PubMed:35773259, PubMed:36008380). May coassemble with CLDN8 into tight junction strands contain", "gene_name": "CLDN4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14493" }, "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "high", "disease": "Gut Dysbiosis", "glycan_involvement": "O-glycosylation critical for mucus gel formation.", "mechanism": "MUC2 maintains mucus layer; loss leads to microbial translocation and inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12446963" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycosylation required for LPS binding.", "mechanism": "CD14 binds LPS, amplifies TLR4 signaling and cytokine release.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "high", "disease": "Chronic Low-grade Inflammation", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "LPS-TLR4 activation triggers NF-\u03baB pathway, driving inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation affects LPS binding and stability.", "mechanism": "Serum LBP levels correlate with endotoxemia and metabolic risk.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC12446963" }, { "confidence": "medium", "disease": "Intestinal Barrier Dysfunction", "glycan_involvement": "Glycosylation modulates adhesion properties.", "mechanism": "JAM-A regulates paracellular permeability; loss increases leakiness.", "protein": "JAM-A", "relationship_type": "causal", "source_pmcid": "PMC12446963" }, { "confidence": "medium", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "FGF19 modulates bile acid reabsorption and hepatic metabolism.", "protein": "FGF19", "protein_enriched": { "function": "Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component o", "gene_name": "CWC22", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HCG8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12446963" }, { "confidence": "medium", "disease": "Metabolic Endotoxemia", "glycan_involvement": "Bacterial glycosylation may affect enzyme stability.", "mechanism": "Degrades intestinal LPS, reducing systemic inflammation.", "protein": "Alkaline Phosphatase (engineered E. coli)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12446963" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "IgA glycosylation is essential for mucosal barrier function.", "mechanism": "Reduced secretory IgA production in poorly controlled diabetes impairs mucosal immunity.", "protein": "Secretory IgA", "relationship_type": "biomarker", "source_pmcid": "PMC12447319" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of IgA critical for neutralization and mucosal transport.", "mechanism": "Higher mucosal IgA correlates with stronger vaccine-induced protection.", "protein": "Secretory IgA", "relationship_type": "protective", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Genital Herpes (HSV-2)", "glycan_involvement": "Glycosylation of gD modulates immune recognition and vaccine efficacy.", "mechanism": "Adenovirus-based vaccines expressing glycoprotein D elicit tissue-resident T-cell responses, reducing viral shedding and lesions.", "protein": "HSV-2 Glycoprotein D", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Genital Herpes (HSV-2)", "glycan_involvement": "Glycan structures on gD affect immunogenicity.", "mechanism": "Subunit vaccines targeting gD failed in clinical trials, indicating its role as a key antigen.", "protein": "HSV-2 Glycoprotein D", "relationship_type": "biomarker", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Porcine Epidemic Diarrhea", "glycan_involvement": "Viral glycoproteins are targets for neutralizing antibodies.", "mechanism": "PEDV glycoprotein antigens fused to immune cell\u2013targeting peptides in SADS-CoV vectors induce protective mucosal immunity in sows and piglets.", "protein": "Porcine Epidemic Diarrhea Virus (PEDV) Antigens", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12447319" }, { "confidence": "medium", "disease": "Nontyphoidal Salmonella Infection", "glycan_involvement": "Glycosylated antigens in EVs enhance immunogenicity.", "mechanism": "Oral delivery of EVs containing Salmonella antigens stimulates antigen-specific IgG and protects mice from lethal challenge.", "protein": "Salmonella Antigens (in EVs)", "relationship_type": "protective", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Helicobacter pylori Infection", "glycan_involvement": "Glycosylation of vaccine antigens improves immune activation.", "mechanism": "Minicell-based vaccines with multi-epitope glycoproteins elicit strong mucosal and systemic immunity, reducing colonization and pathology.", "protein": "Multi-epitope H. pylori Vaccine Proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12447319" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycan modifications on antigens enhance vaccine efficacy.", "mechanism": "Vaccination reduces H. pylori colonization, lowering gastric cancer risk.", "protein": "Multi-epitope H. pylori Vaccine Proteins", "relationship_type": "protective", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Porcine Epidemic Diarrhea", "glycan_involvement": "IgA glycosylation required for neonatal protection.", "mechanism": "Maternal mucosal IgA transferred to piglets confers lactogenic immunity.", "protein": "Secretory IgA", "relationship_type": "protective", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Helicobacter pylori Infection", "glycan_involvement": "Glycosylation of IgA enhances mucosal barrier function.", "mechanism": "Minicell vaccines increase mucosal IgA, reducing H. pylori colonization.", "protein": "Secretory IgA", "relationship_type": "protective", "source_pmcid": "PMC12447319" }, { "confidence": "high", "disease": "Immune regulation disorders", "glycan_involvement": "Core fucosylation of N-glycan at Fc region", "mechanism": "Altered core fucosylation affects IgG binding to Fc receptors, impacting immune response and antibody drug efficacy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12448375" }, { "confidence": "medium", "disease": "Tumor progression", "glycan_involvement": "Core fucosylation of N-glycan", "mechanism": "Changes in IgG core fucosylation can modulate antibody-dependent cellular cytotoxicity, influencing tumor immunity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12448375" }, { "confidence": "high", "disease": "Tumor progression", "glycan_involvement": "Core fucosylation of N-glycan at innermost GlcNAc", "mechanism": "Altered core fucosylation of EGFR changes downstream signaling, affecting cell proliferation and apoptosis.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12448375" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Core fucosylation of N-glycans", "mechanism": "Abnormal core fucose-modified glycoproteins are detected in Alzheimer\u2019s tissues, suggesting early diagnostic potential.", "protein": "Glycoproteins in Alzheimer\u2019s tissues", "relationship_type": "biomarker", "source_pmcid": "PMC12448375" }, { "confidence": "medium", "disease": "Stem cell differentiation defects", "glycan_involvement": "Core fucosylation of high-mannose N-glycans", "mechanism": "Core fucosylation is essential for proper glycoprotein folding and secretion, impacting stem cell differentiation.", "protein": "High-mannose glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12448375" }, { "confidence": "medium", "disease": "Viral infection (Influenza)", "glycan_involvement": "Core fucosylation of viral N-glycans", "mechanism": "Influenza virus modifies surface glycoproteins with core fucose, influencing host immune evasion.", "protein": "Viral surface glycoproteins (Influenza)", "relationship_type": "causal", "source_pmcid": "PMC12448375" }, { "confidence": "high", "disease": "AAMR", "glycan_involvement": "GMPPA regulates GDP-mannose supply for glycosylation; its loss leads to hyperglycosylation.", "mechanism": "Loss-of-function mutations in GMPPA cause AAMR via dysregulation of glycosylation.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "high", "disease": "Achalasia", "glycan_involvement": "Aberrant glycosylation affects neuronal and muscular function in the esophagus.", "mechanism": "GMPPA mutations result in esophageal motility defects as part of AAMR.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "high", "disease": "Mental retardation", "glycan_involvement": "Hyperglycosylation and increased turnover of \u03b1-dystroglycan disrupt neuronal development.", "mechanism": "GMPPA deficiency leads to neurodevelopmental delay via glycosylation defects.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "medium", "disease": "Alacrima", "glycan_involvement": "Glycosylation defects impact lacrimal gland function.", "mechanism": "GMPPA mutations cause tear production defects as part of AAMR.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "high", "disease": "Neurodegeneration", "glycan_involvement": "Hyperglycosylation of \u03b1-dystroglycan impairs neuronal stability.", "mechanism": "Loss of GMPPA function leads to increased \u03b1-dystroglycan turnover and neuron degeneration.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "medium", "disease": "AAMR", "glycan_involvement": "Increased GDP-mannose production enhances glycosylation.", "mechanism": "GMPPA is an allosteric inhibitor of GMPPB; loss of GMPPA increases GMPPB activity.", "protein": "GMPPB", "protein_enriched": { "function": "Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, diff", "gene_name": "DDR1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q08345" }, "relationship_type": "modifier", "source_pmcid": "PMC12449260" }, { "confidence": "high", "disease": "Neurodegeneration", "glycan_involvement": "O-mannosylation of \u03b1-dystroglycan is dysregulated.", "mechanism": "Hyperglycosylation and increased turnover of \u03b1-dystroglycan lead to neuron degeneration.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "high", "disease": "Mental retardation", "glycan_involvement": "Abnormal O-mannosylation affects brain function.", "mechanism": "Defective glycosylation of \u03b1-dystroglycan impairs neuronal development.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "medium", "disease": "Skeletal abnormalities", "glycan_involvement": "Glycosylation defects impact skeletal development.", "mechanism": "GMPPA mutations associated with skeletal defects in AAMR.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "medium", "disease": "Muscular hypotonia", "glycan_involvement": "Hyperglycosylation affects muscle function.", "mechanism": "GMPPA deficiency leads to motor deficits via glycosylation defects.", "protein": "GMPPA", "relationship_type": "causal", "source_pmcid": "PMC12449260" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Elevated fucosylated and sialylated N-glycans (e.g., H5N5F2, H6N5F3S1, H6N5F1S3, H6N5F4S2)", "mechanism": "Altered N-glycosylation (increased fucosylation and sialylation) detected in serum immunoglobulins of AD patients.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12450061" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Hyper-branched di- and trisialylated N-glycans", "mechanism": "Global increases in fucosylation and sialylation on complement factors in AD serum.", "protein": "Complement factors", "relationship_type": "biomarker", "source_pmcid": "PMC12450061" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may promote aggregation", "mechanism": "Aberrant glycosyltransferase activity linked to A\u03b2 aggregation.", "protein": "Amyloid-beta (A\u03b2) protein", "relationship_type": "causal", "source_pmcid": "PMC12450061" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may affect phosphorylation and aggregation", "mechanism": "Aberrant glycosylation associated with tau phosphorylation.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12450061" }, { "confidence": "low", "disease": "Chronic neuroinflammation", "glycan_involvement": "Increased sialylation/fucosylation", "mechanism": "Aberrant glycosylation may contribute to neuroinflammatory processes in AD.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC12450061" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Upregulation of trisialylated N-glycans", "mechanism": "Hyper-branched trisialylated N-glycans (e.g., H6N5F1S3) predict impending cognitive decline.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12450061" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Structural changes in N-glycans", "mechanism": "Altered N-glycosylation patterns linked to cancer progression.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12450061" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CA-125 is a heavily O-glycosylated mucin; glycosylation affects its serum levels and detection.", "mechanism": "Elevated CA-125 observed in SLE-related ascites, reflecting peritoneal inflammation.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is N-glycosylated, which is important for its stability and function.", "mechanism": "Low C3 indicates active SLE due to immune complex consumption.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 is N-glycosylated; glycosylation modulates complement activation.", "mechanism": "Low C4 is a marker of SLE activity and immune complex-mediated inflammation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation affects antibody effector function and immune complex formation.", "mechanism": "Presence and titer correlate with SLE diagnosis and disease activity.", "protein": "Anti-double-stranded DNA antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation may influence immune complex pathogenicity.", "mechanism": "Highly specific for SLE diagnosis.", "protein": "Anti-Smith antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "medium", "disease": "Hypoalbuminemia", "glycan_involvement": "Albumin is minimally glycosylated; glycan changes are not central here.", "mechanism": "Low albumin contributes to ascites by reducing oncotic pressure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates IgG effector function and inflammation.", "mechanism": "Autoantibody (IgG) immune complexes drive SLE pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12450389" }, { "confidence": "medium", "disease": "Pseudo-pseudo Meigs syndrome", "glycan_involvement": "O-glycosylation critical for CA-125 antigenicity.", "mechanism": "Elevated in SLE patients with ascites and pleural effusion, mimicking Meigs syndrome.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation may affect immune complex formation.", "mechanism": "Associated with SLE and mixed connective tissue disease.", "protein": "Anti-RNP antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG glycosylation may modulate pathogenicity.", "mechanism": "Associated with SLE and Sj\u00f6gren\u2019s syndrome overlap.", "protein": "Anti-SS-A antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12450389" }, { "confidence": "high", "disease": "Alport syndrome", "glycan_involvement": "Collagen IV is glycosylated; glycosylation affects stability and assembly.", "mechanism": "Variants in COL4A3, COL4A4, COL4A5 disrupt collagen IV network, impairing kidney filtration, hearing, and vision.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12450471" }, { "confidence": "high", "disease": "Gould syndrome", "glycan_involvement": "Glycosylation modulates collagen IV network formation.", "mechanism": "Variants in COL4A1 and COL4A2 affect \u03b1112 isoform, causing vascular, ocular, muscle, and kidney defects.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12450471" }, { "confidence": "high", "disease": "Junctional epidermolysis bullosa", "glycan_involvement": "Laminin-332 is highly glycosylated, essential for BM assembly and adhesion.", "mechanism": "Defects in LAMA3, LAMB3, LAMC2 disrupt laminin-332, weakening skin BM and causing blistering.", "protein": "Laminin-332", "relationship_type": "causal", "source_pmcid": "PMC12450471" }, { "confidence": "high", "disease": "Dystrophic epidermolysis bullosa", "glycan_involvement": "Collagen VII glycosylation affects fibril stability.", "mechanism": "COL7A1 variants impair anchoring fibrils, causing fragile, blistering skin.", "protein": "Collagen VII", "protein_enriched": { "function": "Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular ", "gene_name": "COL7A1", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q02388" }, "relationship_type": "causal", "source_pmcid": "PMC12450471" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Hemicentin is glycosylated; glycosylation may affect BM linkage.", "mechanism": "Variants in HMCN1 disrupt BM\u2013BM connections in Bruch's membrane, contributing to AMD.", "protein": "Hemicentin", "relationship_type": "risk factor", "source_pmcid": "PMC12450471" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Heparan sulfate chains critical for filtration and growth factor binding.", "mechanism": "Reduced perlecan in ageing/disease correlates with BM dysfunction and interstitial fibrosis.", "protein": "Perlecan", "protein_enriched": { "function": "Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is b", "gene_name": "HSPG2", "glycan_count": 183, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G43417UB", "G57321FI", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G07755XJ", "G08290VR", "G08918WF", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G14972EH", "G20706XG", "G23719VF", "G27058EU", "G27126ED", "G34989PA", "G35029YA", "G36379GD", "G37412TK", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44437FL", "G45395BF", "G45504EY", "G46691LC", "G47702MW", "G49955PK", "G57776ZU", "G59626AS", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G77669RF", "G80920RR", "G83633GK", "G86182NS", "G87661QW", "G90382BL", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G95177YH", "G95865ZB", "G29068FM", "G58001LT", "G73004SD", "G40740AD", "G57317CE", "G53434XO", "G00273SJ", "G01650EU", "G02528FI", "G03382KH", "G04854VP", "G09197ZW", "G10773YW", "G10846ZT", "G11870QZ", "G12341GU", "G14994KB", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G23505EP", "G23863VK", "G23984SE", "G25418HZ", "G25451PN", "G28541PG", "G28681TP", "G29184RN", "G29299MO", "G31028YV", "G31852PQ", "G35253PZ", "G37399XV", "G37509XX", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41840AI", "G44215PV", "G46503DX", "G46687AB", "G46902YN", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51640FO", "G59924QI", "G63041LO", "G65092SV", "G68490OW", "G73430PD", "G73968GN", "G75983OB", "G77547TA", "G79666IR", "G80223IX", "G82463GQ", "G82830MN", "G83646BJ", "G84349RE", "G84452RH", "G84820NF", "G85554PZ", "G87389XI", "G88891KO", "G92062TF", "G96091TT", "G98611JV", "G99679NM", "G01485JJ", "G22572EH", "G27947YN", "G37995HC", "G43669FQ", "G43734MM", "G57776ZS", "G60033FS", "G60834IK", "G75418YA", "G80075MS", "G84862VB", "G86880BF", "G87123QX", "G89045VA", "G91636VS", "G94470IW", "G49108TO", "G22310AV", "G83229XP", "G81006GJ", "G29931IJ", "G02628JF", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G20425TQ", "G23432EQ", "G25079LO", "G26330YA", "G31986NC", "G33609NS", "G37818NZ", "G39188ZX", "G43769HG", "G49906RN", "G52527GH", "G55383ZG", "G64527OM", "G69521XL", "G70223PD", "G72291OX", "G72398FA", "G78790NZ", "G83460ZZ", "G84225JN", "G86795LJ", "G89098OM", "G99668VU" ], "uniprot_id": "P98160" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450471" }, { "confidence": "medium", "disease": "Epidermolysis bullosa", "glycan_involvement": "Integrin glycosylation modulates receptor function.", "mechanism": "Integrin defects impair BM adhesion, contributing to skin fragility.", "protein": "Integrin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12450471" }, { "confidence": "medium", "disease": "Retinal disorders", "glycan_involvement": "Glycosylation affects endostatin release.", "mechanism": "Collagen XVIII-derived endostatin regulates angiogenesis; altered processing linked to retinal disease.", "protein": "Collagen XVIII", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12450471" }, { "confidence": "low", "disease": "Epidermolysis bullosa", "glycan_involvement": "Nidogen glycosylation supports BM interactions.", "mechanism": "Nidogen stabilizes BM; loss disrupts BM integrity, contributing to skin fragility.", "protein": "Nidogen", "relationship_type": "causal (rare forms)", "source_pmcid": "PMC12450471" }, { "confidence": "low", "disease": "Neuromuscular disorders", "glycan_involvement": "Heparan sulfate glycosylation critical for function.", "mechanism": "Agrin defects impair BM signaling at neuromuscular junctions.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12450471" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "O-glycosylation (>50% MW) affects structure, function, and possibly disease association.", "mechanism": "Lacritin promotes tear secretion, immune response, and antimicrobial activity; only therapeutic for DED in clinical trials.", "protein": "Lacritin", "protein_enriched": { "function": "Modulates secretion by lacrimal acinar cells", "gene_name": "LACRT", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q9GZZ8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Site-specific glycoepitopes could distinguish disease states.", "mechanism": "Altered lacritin glycoforms may serve as diagnostic biomarkers for DED.", "protein": "Lacritin", "protein_enriched": { "function": "Modulates secretion by lacrimal acinar cells", "gene_name": "LACRT", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q9GZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "high", "disease": "IgA nephropathy", "glycan_involvement": "Disease-associated O-glycan changes in hinge region.", "mechanism": "Aberrant O-glycosylation (increased Tn/sialyl Tn, decreased sialyl T antigen) in IgA1 hinge region is implicated in pathogenesis.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "causal", "source_pmcid": "PMC12450620" }, { "confidence": "high", "disease": "IgA vasculitis", "glycan_involvement": "Altered O-glycans in hinge region.", "mechanism": "Similar O-glycosylation defects in IgA1 as in IgA nephropathy contribute to disease.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "causal", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Disease-specific N- and O-glycan changes.", "mechanism": "Altered glycosylation of serum IgA1 is associated with ovarian cancer.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Disease-specific N- and O-glycan changes.", "mechanism": "Altered glycosylation of serum IgA1 is associated with breast cancer.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Disease-specific N- and O-glycan changes.", "mechanism": "Altered glycosylation of serum IgA1 is associated with colorectal cancer.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Hepatitis B virus\u2013related liver cancer", "glycan_involvement": "Disease-specific N- and O-glycan changes.", "mechanism": "Altered glycosylation of serum IgA1 is associated with liver cancer.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Altered N-glycosylation may reflect disease state.", "mechanism": "Lactoferrin levels are decreased in DED; N-glycan changes may be disease-associated.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "O-glycosylation critical for mucin function and disease association.", "mechanism": "MUC5AC is essential for ocular surface homeostasis; altered expression/glycosylation may indicate DED.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450620" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "O-glycosylation provides decoy sialic/fucose residues for viral binding.", "mechanism": "Sialylated and fucosylated glycans on MUC1 bind RV particles, blocking viral interaction with epithelial receptors.", "protein": "Mucin 1 (MUC1)", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "O-glycosylation critical for decoy function.", "mechanism": "Sialylated/fucosylated glycans on MUC4 bind RV, preventing epithelial cell entry.", "protein": "Mucin 4 (MUC4)", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation enhances binding to viral proteins.", "mechanism": "Binds RV outer capsid proteins, interfering with viral attachment and entry.", "protein": "Lactadherin", "protein_enriched": { "function": "Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization (By similarity). Contributes to phagocy", "gene_name": "MFGE8", "glycan_count": 69, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01650EU", "G02402FF", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G10773YW", "G14260UH", "G20210JR", "G23294PN", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G48584BU", "G49018RC", "G51640FO", "G51653BI", "G54010QB", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G66538GV", "G70101JE", "G72291OX", "G72735IY", "G72747WU", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G92406TI", "G95865ZB", "G49108TO", "G04657PL", "G08146BT", "G20706XG", "G22310AV", "G23863VK", "G25451PN", "G41071NU", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46691LC", "G51413EV", "G57776ZS", "G57818FI", "G64162JC", "G71146HJ", "G75983OB", "G79666IR", "G81263BG", "G83229XP", "G84452RH", "G86226EA" ], "uniprot_id": "Q08431" }, "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "N-glycosylation essential for VP7 maturation and infectivity.", "mechanism": "Proper glycosylation and disulfide bond formation in VP7 required for infectious virion assembly.", "protein": "VP7 (Rotavirus structural protein)", "protein_enriched": { "function": "Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing t", "gene_name": "15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11187" }, "relationship_type": "causal", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Complex glycan structures competitively inhibit viral attachment.", "mechanism": "HMOs act as soluble decoy receptors, mimicking host cell glycans and blocking RV VP8* binding.", "protein": "Human Milk Oligosaccharides (HMOs)", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation stabilizes sIgA and facilitates mucosal transport.", "mechanism": "sIgA neutralizes RV particles in the gut lumen, preventing infection.", "protein": "Secretory IgA (sIgA)", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation modulates antiviral activity and receptor interactions.", "mechanism": "Binds RV particles and blocks cell surface receptors, inhibiting viral replication.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Host glycan recognition by VP8* is essential for infection.", "mechanism": "VP8* binds host cell surface sialylated glycans (e.g., HBGAs) to mediate viral entry.", "protein": "VP8* (Rotavirus spike protein)", "protein_enriched": { "function": "Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11185" }, "relationship_type": "causal", "source_pmcid": "PMC12450701" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycoprotein glycans act as decoy receptors.", "mechanism": "MFGM components block RV replication by disrupting viral attachment and entry.", "protein": "Milk Fat Globule Membrane (MFGM) proteins", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation may influence EV interaction with viral or host receptors.", "mechanism": "EVs modulate host antiviral responses and may block viral entry via receptor competition.", "protein": "Extracellular Vesicle (EV) glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12450701" }, { "confidence": "high", "disease": "Mortality (all-cause in ADHF)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ECM interactions and inflammatory signaling.", "mechanism": "Upregulated in cardiac inflammation and tissue remodeling; associated with increased mortality.", "protein": "TNC (Tenascin-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "high", "disease": "Rehospitalization for ADHF", "glycan_involvement": "Heparan sulfate glycosylation critical for cell signaling and protective effects.", "mechanism": "Cell surface glycoprotein upregulated after myocardial infarction; overexpression reduces apoptosis and cardiac remodeling.", "protein": "SDC1 (Syndecan-1)", "relationship_type": "protective", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Rehospitalization for ADHF", "glycan_involvement": "Glycosylation required for complement activation and pathogen recognition.", "mechanism": "Pattern recognition glycoprotein involved in lectin complement pathway; associated with inflammation and poor outcomes.", "protein": "FCN2 (Ficolin-2)", "protein_enriched": { "function": "May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide an", "gene_name": "FCN3", "glycan_count": 14, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G07799LX", "G08293MJ", "G08918WF", "G22310AV", "G27058EU", "G31852PQ", "G34989PA", "G41247ZX", "G45395BF", "G59324HL", "G62765YT", "G88374WZ", "G90659AW" ], "uniprot_id": "O75636" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Rehospitalization for ADHF", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Biomarker of insulin resistance; associated with incident hospitalization or mortality in HFpEF.", "protein": "SERPINA12 (Vaspin)", "protein_enriched": { "function": "Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues", "gene_name": "SERPINA12", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8IW75" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Mortality (all-cause in ADHF)", "glycan_involvement": "N-glycosylation modulates cell-cell adhesion and signaling.", "mechanism": "Cell adhesion glycoprotein; higher levels associated with increased mortality.", "protein": "CDH1 (E-cadherin)", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Mortality (all-cause in ADHF)", "glycan_involvement": "Glycosylation may affect intracellular trafficking.", "mechanism": "Fatty acid-binding protein linked to metabolic disease and insulin resistance; associated with increased mortality.", "protein": "FABP6", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Rehospitalization for ADHF", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "TNF receptor superfamily member; higher levels linked to increased risk of rehospitalization.", "protein": "TNFRSF10C", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Diuretic resistance", "glycan_involvement": "Glycosylation affects secretion and substrate specificity.", "mechanism": "Matrix metalloproteinase involved in kidney disease and water reabsorption; associated with reduced diuretic response.", "protein": "MMP7", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "high", "disease": "Diuretic resistance", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Initiates angiotensin cascade leading to salt retention and blunted diuretic response.", "protein": "REN (Renin)", "protein_enriched": { "function": "Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of bloo", "gene_name": "REN", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04689DA", "G05724UK", "G06110VR", "G12932QT", "G14669DU", "G14889BN", "G15956KF", "G16828VN", "G18938DW", "G20425TQ", "G22768VO", "G23863VK", "G23869AA", "G29857RC", "G36191CD", "G39188ZX", "G45359RY", "G47012YE", "G50045TK", "G55220VL", "G63889NK", "G64527OM", "G67381VP", "G72735IY", "G72797UR", "G74724QE", "G78059CC", "G79809MM", "G82348BZ", "G86357DX", "G90093AU", "G93180LE" ], "uniprot_id": "P00797" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "medium", "disease": "Rehospitalization for ADHF", "glycan_involvement": "N-glycosylation required for lysosomal targeting and activity.", "mechanism": "Lysosomal protease involved in tissue remodeling; associated with increased risk of rehospitalization.", "protein": "CTSD (Cathepsin D)", "relationship_type": "biomarker", "source_pmcid": "PMC12450773" }, { "confidence": "high", "disease": "Advanced heart failure", "glycan_involvement": "Not directly discussed; AIM2 is a glycoprotein, glycosylation may affect stability and localization.", "mechanism": "Up-regulated in left and right ventricles, indicating inflammasome activation and contributing to myocardial inflammation/remodelling.", "protein": "AIM2", "protein_enriched": { "function": "Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:17", "gene_name": "AIM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14862" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Advanced heart failure", "glycan_involvement": "Not directly discussed; NLRC4 is a glycoprotein, glycosylation may modulate receptor function.", "mechanism": "Up-regulated in both ventricles, associated with advanced HF and possibly gut-derived antigen sensing.", "protein": "NLRC4", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Pulmonary congestion", "glycan_involvement": "Not directly discussed; NLRP3 is a glycoprotein, glycosylation may affect inflammasome assembly.", "mechanism": "Up-regulated in lung tissue of advanced HF animals, contributing to pulmonary inflammation and congestion.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Pulmonary congestion", "glycan_involvement": "Not directly discussed.", "mechanism": "Elevated in lung tissue of advanced HF, indicating inflammasome activation in pulmonary inflammation.", "protein": "AIM2", "protein_enriched": { "function": "Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:17", "gene_name": "AIM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14862" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Advanced heart failure", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Up-regulated in myocardium and lung, mediates inflammatory damage via inflammasome activation.", "protein": "Pro-IL-1\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12450780" }, { "confidence": "medium", "disease": "Advanced heart failure", "glycan_involvement": "Caspase-1 is glycosylated; glycosylation may regulate activation.", "mechanism": "Up-regulated in myocardium and lung, activates IL-1\u03b2 and IL-18, driving inflammation.", "protein": "Pro-caspase-1", "protein_enriched": { "function": "Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleuki", "gene_name": "CASP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P29466" }, "relationship_type": "causal", "source_pmcid": "PMC12450780" }, { "confidence": "medium", "disease": "Advanced heart failure", "glycan_involvement": "GSDMD is glycosylated; glycosylation may affect membrane targeting.", "mechanism": "Up-regulated in myocardium, mediates pyroptosis downstream of inflammasome activation.", "protein": "GSDMD", "relationship_type": "causal", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Pulmonary congestion", "glycan_involvement": "CD68 is heavily glycosylated; glycosylation is essential for cell surface expression.", "mechanism": "Increased CD68+ leukocyte infiltration in lung tissue, indicating macrophage-driven inflammation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Liver congestion", "glycan_involvement": "Albumin is glycosylated; glycosylation affects stability and half-life.", "mechanism": "Decreased plasma albumin in advanced HF, reflecting hepatic congestion and impaired synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Advanced heart failure", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation affects immunoreactivity and clearance.", "mechanism": "Elevated in plasma of TAC animals, correlates with HF severity.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450780" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation affects \u03b2-TG stability and release from platelets.", "mechanism": "Elevated plasma \u03b2-TG indicates increased in vivo platelet activation in HFpEF.", "protein": "\u03b2-thromboglobulin (\u03b2-TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation modulates CXCL4 secretion and function.", "mechanism": "CXCL4 is elevated in plasma, reflecting aberrant platelet activation in HFpEF.", "protein": "CXCL4 (Platelet Factor 4)", "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation is essential for P-selectin trafficking and adhesion.", "mechanism": "Reduced ex vivo P-selectin expression indicates platelet exhaustion in HFpEF.", "protein": "P-selectin (CD62P)", "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "N-glycosylation regulates integrin activation and ligand binding.", "mechanism": "Decreased activation after GPVI/PAR-1 stimulation; increased after ADP, indicating altered platelet signaling in HFpEF.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation affects MPO secretion and stability.", "mechanism": "Elevated MPO reflects increased neutrophil activation and inflammation in HFpEF.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation modulates S100A8/A9 complex formation and immune signaling.", "mechanism": "Increased S100A8/A9 levels indicate neutrophil activation in HFpEF.", "protein": "S100A8/A9 (Calprotectin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "N-glycosylation is critical for FXI secretion and function.", "mechanism": "Elevated activated FXI (FXIa:C1inh) in HFpEF (especially without anticoagulants) suggests intrinsic pathway activation and procoagulant state.", "protein": "Factor XI", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation regulates kallikrein activation and inhibitor binding.", "mechanism": "Elevated kallikrein (PKa:AT) indicates increased contact activation and coagulation in HFpEF.", "protein": "Kallikrein", "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "medium", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "N-glycosylation modulates ICAM-1 cell surface expression.", "mechanism": "No significant change in ICAM-1 levels between HFpEF and controls; not a marker for endothelial activation in this context.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "medium", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation affects VCAM-1 adhesion properties.", "mechanism": "VCAM-1 levels unaltered in HFpEF; not a marker for endothelial activation here.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450788" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates Fc effector function and charge variants.", "mechanism": "mAbs are used as targeted therapies; glycosylation affects efficacy and safety.", "protein": "Monoclonal antibodies (mAbs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451099" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation at Fc region affects immune effector function.", "mechanism": "Trastuzumab targets HER2+ breast cancer; glycosylation impacts ADCC and pharmacokinetics.", "protein": "Trastuzumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451099" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation impacts charge heterogeneity and drug conjugation sites.", "mechanism": "ADCs deliver cytotoxic drugs to cancer cells; glycosylation influences stability and immunogenicity.", "protein": "Antibody-drug conjugates (ADCs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451099" }, { "confidence": "high", "disease": "Metabolic syndrome/Diabetes", "glycan_involvement": "Non-enzymatic glycation alters protein charge and function.", "mechanism": "AGE-modified proteins accumulate in diabetes, contributing to complications.", "protein": "Advanced glycation end-product (AGE) modified proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Sialylation and glycan branching modulate protein charge and function.", "mechanism": "Altered glycosylation patterns in serum proteins are associated with cardiovascular risk.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Sialylation and glycan modifications alter charge and are detectable by IEC\u2013MS.", "mechanism": "Glycoprotein charge variants in cell lysates reflect tumor heterogeneity.", "protein": "Cell lysate glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "high", "disease": "Therapeutic protein immunogenicity", "glycan_involvement": "Sialylation, glycation, and glycan branching create charge heterogeneity.", "mechanism": "Charge variants due to glycosylation can trigger immune responses.", "protein": "Therapeutic protein variants", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "medium", "disease": "Viral vector efficacy (AAV)", "glycan_involvement": "N-glycosylation modulates charge and infectivity.", "mechanism": "Glycosylation of AAV capsid proteins affects tropism and immune recognition.", "protein": "Adeno-associated virus (AAV) capsid proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "medium", "disease": "Protein misfolding disorders", "glycan_involvement": "N-glycosylation stabilizes structure, reducing misfolding.", "mechanism": "Glycosylation impacts lysozyme folding and aggregation propensity.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "causal", "source_pmcid": "PMC12451099" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "N-glycosylation modulates charge and immune recognition.", "mechanism": "Glycosylation status of ovalbumin influences antigenicity and immune response.", "protein": "Ovalbumin", "relationship_type": "biomarker", "source_pmcid": "PMC12451099" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation of multiple proteins, supporting oncogenic growth", "mechanism": "ALG3 is phosphorylated by AKT downstream of PI3K, promoting N-glycosylation needed for protein folding and proliferation in cancer cells.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Enhanced N-glycosylation of cell surface receptors (EGFR, HER3, E-cadherin)", "mechanism": "ALG3 gene amplification and overexpression promote breast cancer progression; co-amplified with PIK3CA.", "protein": "ALG3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12451169" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation type ALG3 (ALG3-CDG)", "glycan_involvement": "Defective N-glycosylation, accumulation of truncated glycans (Man5-GlcNAc2)", "mechanism": "Loss-of-function mutations in ALG3 cause ALG3-CDG with severe developmental, neurological, and metabolic symptoms.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation at 11 sites; loss leads to deglycosylated, inactive EGFR", "mechanism": "Proper N-glycosylation by ALG3 is required for EGFR folding and activation; loss impairs receptor function and cell proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451169" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation at 10 sites; loss impairs receptor function", "mechanism": "ALG3-dependent N-glycosylation is required for HER3 folding; loss leads to deglycosylated, non-functional HER3.", "protein": "HER3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451169" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation at 4 sites; loss leads to reduced protein levels", "mechanism": "ALG3-dependent N-glycosylation is required for E-cadherin folding and stability; loss impairs cell adhesion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12451169" }, { "confidence": "high", "disease": "ER stress/Unfolded Protein Response (UPR)", "glycan_involvement": "Defective N-glycosylation triggers UPR markers (GRP78/BiP, CHOP)", "mechanism": "ALG3 depletion impairs N-glycosylation, causing accumulation of unfolded proteins and activation of ER stress/UPR.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "medium", "disease": "Developmental and intellectual disabilities", "glycan_involvement": "Impaired N-glycosylation in neural proteins", "mechanism": "ALG3-CDG patients exhibit neurological symptoms due to defective N-glycosylation during development.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "medium", "disease": "Epileptic seizures", "glycan_involvement": "Impaired N-glycosylation in brain", "mechanism": "ALG3-CDG patients develop epilepsy due to defective glycosylation in neuronal proteins.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "medium", "disease": "Metabolic dysfunction (e.g., hypoglycemia)", "glycan_involvement": "Defective N-glycosylation of metabolic proteins", "mechanism": "ALG3-CDG patients have metabolic defects due to impaired glycosylation of metabolic enzymes.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12451169" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP reflects systemic inflammation and correlates with disease severity.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "high", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Minor N-glycosylation may affect ALT secretion and stability.", "mechanism": "Elevated ALT indicates hepatocellular injury, more pronounced in severe cases.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Minor N-glycosylation may modulate AST activity.", "mechanism": "Elevated AST is associated with hypoxia and liver injury in severe COVID-19.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "N-glycosylation critical for ALP stability and activity.", "mechanism": "ALP levels are monitored for cholestatic injury; not significantly altered in this cohort.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "N-glycosylation affects GGT membrane localization.", "mechanism": "GGT is a marker of hepatic and biliary injury; not significantly altered in this study.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Systemic inflammation in COVID-19", "glycan_involvement": "Minor glycosylation may affect half-life and immune interactions.", "mechanism": "Albumin levels decrease in severe inflammation; not significantly altered here.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Pulmonary dysfunction post-COVID", "glycan_involvement": "HDL-associated glycoproteins (e.g., ApoA-I) are glycosylated, affecting function.", "mechanism": "Reduced HDL reflects altered lipid metabolism and may relate to lung injury.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "high", "disease": "Hematological abnormalities in COVID-19", "glycan_involvement": "Surface glycoprotein glycosylation modulates cell trafficking and immune response.", "mechanism": "Elevated WBC counts indicate immune activation in severe COVID-19.", "protein": "WBC surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Multisystem inflammatory syndrome (MIS)", "glycan_involvement": "Glycosylation of CD markers affects lymphocyte signaling and migration.", "mechanism": "Altered lymphocyte counts and activation are linked to MIS.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "medium", "disease": "Thromboinflammation in COVID-19", "glycan_involvement": "CD14 glycosylation modulates monocyte activation and cytokine release.", "mechanism": "Elevated monocyte counts contribute to thromboinflammatory responses.", "protein": "Monocyte surface glycoproteins (CD14)", "relationship_type": "biomarker", "source_pmcid": "PMC12452437" }, { "confidence": "high", "disease": "Toxoplasmosis", "glycan_involvement": "Chitin polysaccharide in cyst wall is substrate; glycosylation critical for cyst integrity.", "mechanism": "Regulates chitin degradation in cyst wall, affecting parasite reactivation and disease progression.", "protein": "Chitinase-like protein 1", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Nosocomial infections (Acinetobacter pittii)", "glycan_involvement": "CPS is a glycan barrier; its degradation exposes bacteria to immune attack.", "mechanism": "CPS protects bacteria from host defenses; depolymerase enzyme degrades CPS, increasing susceptibility to immune killing.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Antimicrobial resistance (AMR) infections", "glycan_involvement": "Targets glycan capsule for degradation.", "mechanism": "Depo27 degrades CPS of A. pittii, rendering bacteria susceptible to serum-mediated killing.", "protein": "Depolymerase enzyme (Depo27)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Gastritis", "glycan_involvement": "LPS glycan structure modulates immune stimulation.", "mechanism": "Truncated LPS in H. pylori mutants reduces innate immune response, potentially lowering chronic inflammation.", "protein": "Lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "medium", "disease": "Ulcers", "glycan_involvement": "LPS glycosylation affects inflammatory signaling.", "mechanism": "Chronic inflammation from LPS-induced immune response contributes to ulcer formation.", "protein": "Lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "medium", "disease": "Cancer (gastric)", "glycan_involvement": "LPS glycan structure influences chronic inflammation.", "mechanism": "Chronic LPS-driven inflammation may promote carcinogenesis.", "protein": "Lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Glycosylation and fatty acid patterns of Lipid A modulate host immune response.", "mechanism": "c-di-AMP regulates LPS/Lipid A glycosylation in P. gingivalis, affecting immunostimulatory potential and disease progression.", "protein": "Lipid A variants", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "c-di-AMP controls glycan composition of LPS.", "mechanism": "Targeting c-di-AMP network alters LPS glycosylation, potentially reducing P. gingivalis survival.", "protein": "Cyclic-di-AMP network proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Neisseria infection", "glycan_involvement": "Phase-variable O-glycosylation alters antigenicity.", "mechanism": "O-glycosylation and glycan heterogeneity of pilin enable immune evasion and persistent infection.", "protein": "Pilin", "relationship_type": "causal", "source_pmcid": "PMC12454420" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycan modifications affect host-pathogen interactions.", "mechanism": "Glycosylation of surface proteins modulates immunogenicity and virulence, impacting sepsis outcomes.", "protein": "Flagellin/S-layer proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12454420" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Disruption of N-glycosylation alters inactivation delay, impacting neuronal signaling.", "mechanism": "Kv3.4 modulates neuronal excitability; altered N-glycosylation affects channel kinetics, contributing to pathogenesis.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Impaired N-glycosylation reduces kinetic heterogeneity, promoting hyperexcitability.", "mechanism": "Kv3.4 regulates high-frequency firing; N-glycosylation defects lead to abnormal excitability and seizures.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "medium", "disease": "Chronic pain", "glycan_involvement": "N-glycosylation state determines inactivation kinetics, affecting pain pathways.", "mechanism": "Kv3.4 dysfunction alters pain signaling; glycosylation modulates channel activity.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates gating properties relevant to cardiac tissue.", "mechanism": "Kv3.4 influences cardiac excitability; glycosylation affects channel function.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "N-glycosylation impacts channel stability and function in cancer cells.", "mechanism": "Kv3.4 kinetics are altered in cancer; glycosylation affects cell proliferation and signaling.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "high", "disease": "Congenital disorders of glycosylation (CDG)", "glycan_involvement": "Defective N-glycosylation disrupts Kv3.4 kinetics and neuronal excitability.", "mechanism": "CDGs cause global glycosylation defects; Kv3.4 function is impaired, leading to neurological symptoms.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "high", "disease": "GLUT1 deficiency syndrome", "glycan_involvement": "Low glucose limits N-glycosylation, altering Kv3.4 function.", "mechanism": "GLUT1 deficiency reduces glucose supply, impairing N-glycosylation of Kv3.4 and causing seizures and developmental delay.", "protein": "Kv3.4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation disruption reduces kinetic heterogeneity, affecting excitability.", "mechanism": "Kv1.3 N-glycosylation modulates channel kinetics; defects may contribute to seizure susceptibility.", "protein": "Kv1.3", "protein_enriched": { "function": "Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a", "gene_name": "KCNA3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P22001" }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates gating and inactivation delay.", "mechanism": "Kv1.5 N-glycosylation affects cardiac channel kinetics; defects may contribute to arrhythmias.", "protein": "Kv1.5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "high", "disease": "GLUT1 deficiency syndrome", "glycan_involvement": "Glucose availability is essential for N-glycosylation of Kv channels.", "mechanism": "GLUT1 mutations impair glucose transport, reducing N-glycosylation of Kv3.4 and other glycoproteins, leading to neurological symptoms.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12455010" }, { "confidence": "medium", "disease": "Age-related blood-brain barrier dysfunction", "glycan_involvement": "\u03b2-dystroglycan is heavily glycosylated; glycosylation is essential for its function in basement membrane interactions.", "mechanism": "Increased \u03b2-dystroglycan expression in hippocampal astrocyte endfeet with age indicates BBB molecular alteration.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "high", "disease": "Increased BBB permeability", "glycan_involvement": "Caveolin-1 is a glycoprotein; glycosylation may affect its trafficking and function.", "mechanism": "Upregulation of caveolin-1 in prefrontal cortex endothelial cells increases caveolae-mediated transcytosis, leading to higher BBB permeability with age.", "protein": "Caveolin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the re", "gene_name": "Cav1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49817" }, "relationship_type": "causal", "source_pmcid": "PMC12455408" }, { "confidence": "medium", "disease": "Age-related blood-brain barrier dysfunction", "glycan_involvement": "Claudin-5 is N-glycosylated, which may influence tight junction assembly.", "mechanism": "No significant change in claudin-5 expression or tight junction tortuosity with early ageing, suggesting preserved paracellular barrier.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "medium", "disease": "Brain edema", "glycan_involvement": "AQP-4 is glycosylated; glycosylation affects membrane localization.", "mechanism": "No age-associated change in AQP-4 polarization in astrocyte endfeet, suggesting water homeostasis is maintained at early ageing.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "medium", "disease": "Astrocyte endfoot hypertrophy", "glycan_involvement": "Dystrophin interacts with glycosylated dystroglycan complex.", "mechanism": "No change in dystrophin expression with age; however, endfoot hypertrophy in prefrontal cortex suggests altered cytoskeletal dynamics.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "medium", "disease": "Basement membrane thickening", "glycan_involvement": "Glycosylation of \u03b2-dystroglycan mediates its interaction with ECM proteins.", "mechanism": "\u03b2-dystroglycan upregulation may contribute to increased basement membrane thickness in aged prefrontal cortex.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12455408" }, { "confidence": "low", "disease": "Cerebral small vessel disease", "glycan_involvement": "PECAM-1 is N-glycosylated, which regulates cell adhesion.", "mechanism": "PECAM-1 used as an endothelial marker; no age-related change observed, suggesting limited involvement in early BBB ageing.", "protein": "PECAM-1", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for eff", "gene_name": "Pecam1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G25079LO", "G24748EV", "G15664MX", "G72747WU", "G31986NC", "G80920RR", "G49108TO" ], "uniprot_id": "Q08481" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "low", "disease": "Age-related blood-brain barrier dysfunction", "glycan_involvement": "CD13 is a glycoprotein; glycosylation affects enzymatic activity.", "mechanism": "CD13 (pericyte marker) coverage unchanged with age, indicating pericyte stability at early ageing.", "protein": "CD13", "protein_enriched": { "function": "Mediates the anchoring of the endoplasmic reticulum to microtubules", "gene_name": "CKAP4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "Q07065" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "medium", "disease": "Sex-dependent BBB vulnerability", "glycan_involvement": "Glycosylation may modulate caveolin-1 function.", "mechanism": "Caveolin-1 expression higher in females in prefrontal cortex and hippocampus, suggesting sex differences in BBB ageing.", "protein": "Caveolin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the re", "gene_name": "Cav1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49817" }, "relationship_type": "biomarker", "source_pmcid": "PMC12455408" }, { "confidence": "low", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation critical for \u03b2-dystroglycan's ECM interactions.", "mechanism": "Altered \u03b2-dystroglycan expression in hippocampus may contribute to region-specific BBB vulnerability and cognitive decline.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12455408" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "N-linked glycans on NA stalk promote functional tetramer formation and viral fitness.", "mechanism": "NA is essential for viral propagation by cleaving sialic acid receptors, balancing HA function.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycans shield hydrophobic regions, preventing proteolytic cleavage.", "mechanism": "Stalk N-linked glycans reduce susceptibility to proteolysis, protecting NA integrity.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycosylation modulates antigenicity and immunogenicity of NA.", "mechanism": "NA is a target for antiviral drugs and vaccine antigens.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12456132" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "Temporal increase in stalk glycan sites linked to pandemic strain adaptation.", "mechanism": "Number and position of N-linked glycan sites in NA stalk correlate with viral fitness and evolution.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycans compensate for local hydrophobicity, enabling proper NA assembly.", "mechanism": "Loss of multiple stalk N-linked glycans impairs viral growth; compensatory polar mutations restore fitness.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycosylation status affects yield and activity of recombinant vaccine antigens.", "mechanism": "Recombinant NA antigens lacking stalk glycans require polar substitutions for functional expression.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12456132" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "N-linked glycans on HA shield epitopes, contributing to immune evasion.", "mechanism": "HA mediates viral entry by binding sialic acid; glycosylation modulates antigenicity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12456132" }, { "confidence": "medium", "disease": "Influenza A (H5N1)", "glycan_involvement": "Loss of stalk glycans and hydrophobic domains alters NA function.", "mechanism": "NA stalk truncations in H5N1 remove hydrophobic regions and glycan sites, affecting viral properties.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12456132" }, { "confidence": "medium", "disease": "Influenza A (H1N1)", "glycan_involvement": "Glycosylation shields NA stalk from antibody recognition.", "mechanism": "Stalk glycans may mask antigenic regions, contributing to immune evasion.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Manipulation of glycosylation and hydrophobicity enhances vaccine design.", "mechanism": "Structure-guided antigen engineering of NA stalk improves recombinant antigen yield and immunogenicity.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12456132" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "N-glycosylation of MOG influences antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG trigger CNS demyelination and inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "high", "disease": "Optic neuritis (ON)", "glycan_involvement": "Glycosylation modulates MOG's immune interactions.", "mechanism": "MOG autoantibodies mediate inflammatory demyelination of the optic nerve.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "medium", "disease": "Amaurosis fugax dolorosa", "glycan_involvement": "Glycosylation may affect MOG's immunogenicity and prodromal symptom development.", "mechanism": "Painful transient visual loss (AF) is a prodromal symptom of MOGAD ON.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12456432" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (AQP4+NMOSD)", "glycan_involvement": "Glycosylation affects AQP4 antibody binding and pathogenicity.", "mechanism": "AQP4 autoantibodies cause astrocyte damage and demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "high", "disease": "Optic neuritis (ON)", "glycan_involvement": "N-glycosylation impacts MOG antibody recognition.", "mechanism": "MOG antibodies are diagnostic for MOGAD ON.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12456432" }, { "confidence": "medium", "disease": "Amaurosis fugax dolorosa", "glycan_involvement": "Glycosylation may modulate inflammatory response.", "mechanism": "MOGAD-related inflammation may cause transient optic nerve dysfunction preceding ON.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "medium", "disease": "Optic neuritis (ON)", "glycan_involvement": "Glycosylation status may affect MOG's immunogenicity and response to therapy.", "mechanism": "Steroid therapy improves ON in MOGAD patients.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12456432" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "N-glycosylation influences antibody binding.", "mechanism": "High-titer MOG antibodies confirm diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12456432" }, { "confidence": "medium", "disease": "Optic neuritis (ON)", "glycan_involvement": "Glycosylation affects AQP4 antibody interactions.", "mechanism": "AQP4 antibodies can cause ON in NMOSD, but AF prodrome is absent.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "medium", "disease": "Optic neuritis (ON)", "glycan_involvement": "Glycosylation may influence MOG's role in vascular inflammation.", "mechanism": "Perivenular and perivascular inflammation in MOGAD ON may extend to small arteries, causing prodromal AF.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12456432" }, { "confidence": "high", "disease": "Diabetic Cardiomyopathy (DCM)", "glycan_involvement": "Non-enzymatic glycation of proteins and lipids.", "mechanism": "AGEs accumulate in myocardium, increase collagen cross-linking, promote fibrosis and diastolic dysfunction.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Recognition of glycated proteins by glycoprotein receptor.", "mechanism": "AGEs bind RAGE, activating inflammation and ROS, leading to cardiomyocyte apoptosis and fibrosis.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and clearance.", "mechanism": "Elevated BNP indicates myocardial stretch and predicts progression to symptomatic HF.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein fragment; glycosylation affects half-life.", "mechanism": "Elevated NT-proBNP is predictive of HF risk and guides early intervention in T2DM.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Elevated hs-cTnT reflects subclinical myocardial injury and predicts HF onset.", "protein": "hs-cTnT", "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Secreted glycoprotein; glycosylation influences function.", "mechanism": "sST2 correlates with early myocardial fibrosis and adverse cardiovascular events in T2DM.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Microalbuminuria", "glycan_involvement": "Glycosylation status may affect renal handling.", "mechanism": "Elevated urinary albumin (uACR) predicts HF risk in T2DM and CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "Higher HbA1c levels independently predict increased HF risk in T2DM.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Binds \u03b2-galactosides; glycosylation modulates activity.", "mechanism": "Galectin-3 is associated with early myocardial fibrosis and metabolic dysregulation.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12457163" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Membrane glycoprotein; glycosylation affects enzyme activity.", "mechanism": "ACE inhibitors reduce hypertension and proteinuria, lowering HF risk in T2DM.", "protein": "ACE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12457163" }, { "confidence": "low", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "Glycosylation of MOG is essential for its immunogenicity and interaction with immune cells.", "mechanism": "Oral administration of MOG attenuates EAE by inducing Th2/Treg cells and suppressing Th1/Th17 responses.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12458824" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated fatty liver disease (MAFLD)", "glycan_involvement": "AGP is heavily N-glycosylated; glycosylation modulates its acute-phase and immunomodulatory functions.", "mechanism": "AGP elevation reflects systemic and hepatic inflammation associated with metabolic dysfunction and steatosis.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects AGP's anti-inflammatory and immunomodulatory properties.", "mechanism": "AGP levels are linked to systemic inflammation, a risk factor for cardiovascular disease.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Altered glycosylation may influence AGP's interaction with immune cells.", "mechanism": "AGP is elevated in metabolic dysregulation and chronic inflammation seen in diabetes.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation status may affect AGP's stability and function in obesity.", "mechanism": "AGP is upregulated in obesity-related inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation modulates AGP's acute-phase response.", "mechanism": "AGP reflects inflammatory milieu accompanying hepatic fat accumulation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "low", "disease": "Advanced fibrosis", "glycan_involvement": "N-glycosylation may influence AGP's role in immune signaling during fibrosis.", "mechanism": "AGP elevation may indicate progression from steatosis to fibrotic liver disease.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation changes may occur in advanced liver disease.", "mechanism": "AGP may be elevated in cirrhosis due to chronic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns may be present in cancer.", "mechanism": "AGP elevation is associated with chronic liver inflammation, a risk factor for HCC.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated fatty liver disease (MAFLD)", "glycan_involvement": "N-glycosylation enables AGP's stability and function as a serum biomarker.", "mechanism": "Nonlinear dose\u2013response: AGP is most predictive of MAFLD risk below ~0.9 g/L, with plateau at higher levels.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "risk stratification biomarker", "source_pmcid": "PMC12459064" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated fatty liver disease (MAFLD)", "glycan_involvement": "Glycosylation is essential for AGP's acute-phase reactivity and serum half-life.", "mechanism": "AGP outperforms liver enzymes in early MAFLD detection due to sensitivity to low-grade inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker (superior to ALT/AST)", "source_pmcid": "PMC12459064" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation modulates AAG's immunomodulatory function.", "mechanism": "AAG is an acute-phase protein elevated during systemic inflammation.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "high", "disease": "Metabolic dysfunction", "glycan_involvement": "Glycosylation pattern may affect metabolic regulatory roles.", "mechanism": "Elevated AAG correlates with increased adiposity and BMI.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Altered glycosylation may influence AAG's inflammatory activity.", "mechanism": "High AAG levels are associated with increased cardiovascular risk.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation may be altered in obesity, affecting AAG function.", "mechanism": "AAG levels rise with increased adiposity and BMI.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation changes may modulate inflammatory signaling.", "mechanism": "Chronic inflammation marked by elevated AAG is linked to diabetes risk.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation may affect AAG's role in acute-phase response.", "mechanism": "High AAG levels predict increased risk of myocardial infarction.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may influence AAG's inflammatory properties.", "mechanism": "Elevated AAG is associated with higher stroke risk.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "low", "disease": "Cancer (breast)", "glycan_involvement": "Glycosylation may affect AAG's interaction with immune cells.", "mechanism": "AAG and other inflammatory markers mediate risk disparities in breast cancer.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "Diet can alter AAG glycosylation, affecting its inflammatory profile.", "mechanism": "AAG is elevated in chronic low-grade inflammatory states.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "medium", "disease": "Mortality (all-cause)", "glycan_involvement": "Glycosylation status may influence AAG's prognostic value.", "mechanism": "High AAG levels are linked to increased all-cause mortality.", "protein": "\u03b1-1-acid glycoprotein (AAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12459478" }, { "confidence": "high", "disease": "Candida auris infection", "glycan_involvement": "Glycosylation of cell wall proteins is essential for fungal virulence and resistance.", "mechanism": "Cell wall glycoproteins mediate adhesion, immune evasion, and persistence in healthcare environments.", "protein": "Candida auris cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12460727" }, { "confidence": "high", "disease": "Healthcare-associated infection (HAI)", "glycan_involvement": "Glycan structures on cell wall proteins contribute to environmental persistence and transmission.", "mechanism": "Glycoproteins facilitate colonization and transmission in hospital settings.", "protein": "Candida auris cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12460727" }, { "confidence": "high", "disease": "CDG (general)", "glycan_involvement": "Defective N-glycosylation leads to altered ICAM1 glycoforms.", "mechanism": "Incomplete or missing glycan chains detected on ICAM1 in CDG patients.", "protein": "Intercellular Adhesion Molecule 1", "relationship_type": "biomarker", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "CDG (general)", "glycan_involvement": "Defective N-glycosylation results in abnormal transferrin isoforms.", "mechanism": "Altered glycosylation pattern of transferrin used for CDG diagnosis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "Reduced UDP-glucose and UDP-galactose for N-glycosylation.", "mechanism": "PGM1 deficiency disrupts interconversion of Glc-6-P and Glc-1-P, impairing glycan precursor synthesis.", "protein": "Phosphoglucomutase 1", "relationship_type": "causal", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "Galactose increases UDP-galactose and UDP-glucose, rescuing glycosylation defects.", "mechanism": "Galactose supplementation restores hexose-phosphate levels and improves glycosylation.", "protein": "Phosphoglucomutase 1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "Altered hexose-phosphate metabolism affects glycan biosynthesis.", "mechanism": "Disturbed levels of Glc-1-P, Glc-6-P, Gal-1-P, and Gal-6-P in patient fibroblasts.", "protein": "Phosphoglucomutase 1", "relationship_type": "biomarker", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Reduced Man-1-P affects N-glycan precursor synthesis.", "mechanism": "PMM2 deficiency impairs mannose metabolism, leading to glycosylation defects.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "causal", "source_pmcid": "PMC12461406" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Further loss of Man-1-P exacerbates glycosylation deficiency.", "mechanism": "Galactose supplementation is ineffective and may worsen Man-1-P depletion.", "protein": "PMM2 (Phosphomannomutase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "Alternative pathway for glycan precursor synthesis.", "mechanism": "Galactose-derived Gal-1-P and UDP-galactose bypass PGM1 block, restoring glycosylation.", "protein": "Phosphoglucomutase 1", "relationship_type": "protective", "source_pmcid": "PMC12461406" }, { "confidence": "medium", "disease": "PGM1-CDG", "glycan_involvement": "Gal-6-P formation linked to glycosylation pathway flux.", "mechanism": "Low Gal-6-P levels in PGM1-CDG fibroblasts indicate impaired galactose metabolism.", "protein": "Phosphoglucomutase 1", "relationship_type": "biomarker", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "PGM1-CDG", "glycan_involvement": "N-glycosylation defects detectable by transferrin isoelectric focusing.", "mechanism": "Altered transferrin glycoforms reflect glycosylation status in PGM1-CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12461406" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation affects secretion and stability; EV-associated ADIPOQ reflects adipocyte glycosylation status.", "mechanism": "Downregulated in EVs in obesity with diabetes; upregulated after bariatric surgery and associated with improved glycemic control.", "protein": "Adiponectin (ADIPOQ)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12463671" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "MBL2 is a lectin recognizing mannose glycans; glycosylation critical for function.", "mechanism": "Downregulated with increased BMI; upregulated after bariatric surgery, associated with improved insulin sensitivity.", "protein": "Mannose Binding Lectin 2 (MBL2)", "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "LUM is a proteoglycan with keratan sulfate chains; glycosylation modulates ECM interactions.", "mechanism": "Upregulated in obesity with diabetes; impairs adipogenesis and insulin sensitivity, remains elevated after bariatric surgery.", "protein": "Lumican (LUM)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12463671" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation required for IgA/IgM transport; glycan status affects immune function.", "mechanism": "Upregulated in diabetes/obesity; downregulated after bariatric surgery, reflecting reduced inflammation.", "protein": "Polymeric Immunoglobulin Receptor (PIGR)", "protein_enriched": { "function": "Mediates selective transcytosis of polymeric IgA and IgM across mucosal epithelial cells. Binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported ac", "gene_name": "PIGR", "glycan_count": 323, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G06247RL", "G08146BT", "G08918WF", "G10819WX", "G10846ZT", "G11870QZ", "G12313PD", "G14972EH", "G14994KB", "G18647XP", "G20312EM", "G22310AV", "G25418HZ", "G27058EU", "G27126ED", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G42962KI", "G43223CG", "G43669FQ", "G44215PV", "G45395BF", "G45495MK", "G45526EA", "G46687AB", "G46691LC", "G48414YA", "G50856PC", "G52527GH", "G57776ZS", "G59324HL", "G59626AS", "G59924QI", "G60834IK", "G62765YT", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G71146HJ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82443XX", "G82830MN", "G83229XP", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G93718GY", "G95865ZB", "G99668VU", "G00273SJ", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05962QB", "G06110VR", "G06356OH", "G06830JN", "G07246CJ", "G08290VR", "G10486CT", "G11314AS", "G11911BT", "G13131HA", "G14669DU", "G15169WU", "G15664MX", "G20706XG", "G23294PN", "G23863VK", "G24835MQ", "G25079LO", "G25451PN", "G26330YA", "G26403SG", "G27947YN", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30740WO", "G31118FR", "G31916IQ", "G37399XV", "G37412TK", "G37818NZ", "G37868ZX", "G40574BA", "G40926MX", "G42124LM", "G42358LZ", "G44753VC", "G45504EY", "G46902YN", "G47644PP", "G47950XN", "G49755GI", "G49906RN", "G50045TK", "G56518TU", "G57818FI", "G60033FS", "G64527OM", "G65184UU", "G69521XL", "G70888PK", "G72291OX", "G72667IM", "G72747WU", "G72797UR", "G74724QE", "G76295SF", "G77669RF", "G81263BG", "G82119TF", "G82463GQ", "G84862VB", "G86182NS", "G87123QX", "G90382BL", "G91473PK", "G91636VS", "G92050GC", "G92081HT", "G92551JA", "G94470IW", "G98611JV", "G99679NM", "G99966GV", "G01160VV", "G05049YU", "G07755XJ", "G07810QS", "G09831WQ", "G11101UV", "G11629QQ", "G12341GU", "G13910DJ", "G17208MA", "G20528HD", "G23719VF", "G30221QT", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G43734MM", "G44778BV", "G51413EV", "G51640FO", "G53075ES", "G55132BD", "G55383ZG", "G58954YZ", "G60177UT", "G60967DT", "G61256FT", "G63980BQ", "G64409MC", "G65019XG", "G66621EA", "G67164EE", "G71463BG", "G72197KC", "G73968GN", "G76613WN", "G77240OA", "G78649WQ", "G78787DI", "G80479JV", "G81198YO", "G81637OR", "G83460ZZ", "G85677PP", "G89045VA", "G89827JR", "G90734RJ", "G92275SC", "G95177YH", "G95977AE", "G96577RX", "G01485JJ", "G02528FI", "G10256JP", "G10773YW", "G16125XL", "G22140GZ", "G22625SJ", "G23505EP", "G27915IV", "G28541PG", "G29880MM", "G37509XX", "G41247ZX", "G43769HG", "G46503DX", "G47012YE", "G47518TP", "G49874UX", "G50427EO", "G51653BI", "G52890YB", "G61937QU", "G63041LO", "G63136LV", "G63381RX", "G65414LI", "G66163OV", "G66760KM", "G70223PD", "G72787SB", "G74430RZ", "G75607BQ", "G77547TA", "G79286RS", "G79568CQ", "G81295CK", "G85554PZ", "G87389XI", "G88374WZ", "G90575OW", "G92406TI", "G94854LT", "G02315DX", "G05724UK", "G13728QT", "G14260UH", "G20210JR", "G20425TQ", "G23453IV", "G24084IV", "G24954UD", "G25637MV", "G27516OE", "G30769VJ", "G31028YV", "G31596VW", "G33609NS", "G34617SM", "G35029YA", "G37692EO", "G37881RL", "G39064KU", "G39188ZX", "G39446WN", "G40206WX", "G41840AI", "G45883VE", "G49955PK", "G55220VL", "G57317CE", "G57776ZU", "G59536GA", "G62837OZ", "G65540UB", "G66676MI", "G67506FN", "G70101JE", "G70375MX", "G72735IY", "G72790NZ", "G76329HL", "G77459ND", "G78790NZ", "G80966KZ", "G81375TC", "G82020ZR", "G84820NF", "G86234IN", "G86408JD", "G89098OM", "G90093AU", "G99858XP", "G81006GJ", "G22355FZ", "G76163CP", "G74722FL", "G01521EA", "G03127AL", "G08110WX", "G14796IU", "G21643DJ", "G26759AS", "G27251WT", "G31309XD", "G50006QM", "G52114WE", "G60145BJ", "G64751KD", "G85228QD", "G02628JF", "G19116TW", "G32332VU", "G54612UD", "G54982TL", "G56284ZY", "G64162JC", "G66766XF", "G93683YO", "G47447OK", "G49108TO", "G54285KU" ], "uniprot_id": "P01833" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Heavily glycosylated; glycan modifications affect platelet function.", "mechanism": "Downregulated in diabetes/obesity; upregulated after bariatric surgery in diabetes, may reflect platelet activation status.", "protein": "Glycoprotein V Platelet (GP5)", "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects transport and stability.", "mechanism": "Upregulated in diabetes/obesity; correlates with BMI, serum glucose, and weight loss after surgery.", "protein": "Afamin (AFM)", "protein_enriched": { "function": "Functions as a carrier for hydrophobic molecules in body fluids (Probable). Essential for the solubility and activity of lipidated Wnt family members, including WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A,", "gene_name": "AFM", "glycan_count": 68, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10179FS", "G10486CT", "G14972EH", "G22140GZ", "G22310AV", "G45395BF", "G48414YA", "G50045TK", "G59626AS", "G61256FT", "G62765YT", "G77669RF", "G92551JA", "G94470IW", "G56784JY", "G57888GL", "G02886BB", "G10846ZT", "G11911BT", "G20528HD", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G40574BA", "G40834TG", "G41071NU", "G42358LZ", "G57317CE", "G57776ZU", "G64527OM", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G75983OB", "G80920RR", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G87661QW", "G89098OM", "G95865ZB", "G98611JV", "G01650EU", "G11870QZ", "G15169WU", "G20425TQ", "G23863VK", "G27947YN", "G31118FR", "G36131WL", "G40926MX", "G43089EG", "G47518TP", "G47737VJ", "G57776ZS", "G75798PH", "G81295CK", "G88374WZ", "G94917XT" ], "uniprot_id": "P43652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Contains O-glycosylation sites; glycosylation may affect secretion.", "mechanism": "Upregulated after bariatric surgery in diabetes/obesity; associated with weight loss and angiogenesis.", "protein": "Hornerin (HRNR)", "protein_enriched": { "function": "Component of the epidermal cornified cell envelopes", "gene_name": "HRNR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86YZ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "low", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation may affect protease activity.", "mechanism": "Downregulated in diabetes/obesity; upregulated after bariatric surgery in diabetes.", "protein": "Serine Protease 3 (PRSS3)", "protein_enriched": { "function": "Digestive protease that cleaves proteins preferentially after an Arg residue and has proteolytic activity toward Kunitz-type trypsin inhibitors", "gene_name": "PRSS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35030" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation modulates CRP function and clearance.", "mechanism": "Upregulated in obesity; associated with BMI and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation affects stability and immune interactions.", "mechanism": "Upregulated in obesity; associated with BMI and inflammatory status.", "protein": "Serum Amyloid A1 (SAA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12463671" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via binding to ACE2 and fusion with host membrane.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects ACE2 stability and spike binding.", "mechanism": "Acts as the main entry receptor for SARS-CoV-2; upregulated in obesity.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and localization.", "mechanism": "Cleaves spike protein, facilitating viral entry; expression increased in obese macrophages.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Alternative receptor for spike protein, mediates endosomal viral entry.", "protein": "AXL", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell", "gene_name": "AXL", "glycan_count": 14, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G27058EU", "G84452RH", "G11629QQ", "G12793SR", "G15169WU", "G48414YA", "G52527GH", "G60834IK", "G62765YT", "G81263BG", "G89205CJ", "G93656SY", "G90575OW" ], "uniprot_id": "P30530" }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect membrane localization and antiviral activity.", "mechanism": "Restricts viral entry and fusion; expression increased in obese macrophages.", "protein": "IFITM3", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P14210" }, "relationship_type": "protective", "source_pmcid": "PMC12464564" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Spike glycosylation interacts with host glycoproteins.", "mechanism": "Obesity increases ACE2 and TMPRSS2 expression, enhancing spike-mediated viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "low", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "N-glycosylation may modulate ACE2 expression in liver tissue.", "mechanism": "ACE2 upregulation in MASLD increases risk of liver injury in COVID-19.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12464564" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates immune recognition and inflammation.", "mechanism": "Spike-induced cytokine storm contributes to ARDS pathogenesis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein function and immune evasion.", "mechanism": "E protein involved in viral assembly and pathogenesis.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence viral particle stability.", "mechanism": "M protein critical for viral assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC12464564" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Reflects neuroinflammation and tissue remodeling; elevated in plasma and CSF in AD.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycosylation affects lysosomal trafficking.", "mechanism": "Upregulated in choroid plexus and plasma; linked to lysosomal dysfunction and CP barrier impairment.", "protein": "TMEM106B", "protein_enriched": { "function": "Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the", "gene_name": "MGAT4A", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9UM21" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation essential for secretion and receptor binding.", "mechanism": "Elevated in serum; reflects vascular stress and compensatory response to BBB damage.", "protein": "Angiopoietin-1 (Ang-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates protease inhibitor function.", "mechanism": "Elevated in plasma; impairs endothelial repair, increases BBB leakage, and correlates with tau pathology.", "protein": "Alpha-2-macroglobulin (A2M)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12465532" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation influences lipid binding and plasma half-life.", "mechanism": "Altered plasma levels; modulates lipid metabolism, inflammation, and BBB integrity.", "protein": "Apolipoprotein C1 (ApoC1)", "protein_enriched": { "function": "Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoprotein", "gene_name": "APOC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02654" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects stability and A\u03b2 binding.", "mechanism": "Reduced in plasma/CSF; binds A\u03b2, prevents aggregation, and supports A\u03b2 clearance.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "Elevated in plasma; degrades tight junctions in CP and BBB, promoting barrier dysfunction.", "protein": "Matrix metalloproteinase 9 (MMP-9)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12465532" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for protease inhibitor function.", "mechanism": "Elevated in serum; reflects neuroinflammation and BBB leakage.", "protein": "Pregnancy zone protein (PZP)", "relationship_type": "biomarker", "source_pmcid": "PMC12465532" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Minor O-glycosylation; not primary for function.", "mechanism": "Elevated in plasma; reflects astrocyte activation and correlates with CP volume changes.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12465532" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Increased soluble form in CSF/serum; indicates pericyte loss and BBB disruption.", "protein": "Platelet-derived growth factor receptor-\u03b2 (PDGFR\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC12465532" }, { "confidence": "high", "disease": "Glucose intolerance", "glycan_involvement": "ApoER2 is a glycoprotein; glycosylation may affect receptor function but not directly studied here.", "mechanism": "Endothelial-specific deletion of ApoER2 impairs insulin delivery to skeletal muscle, leading to glucose intolerance.", "protein": "ApoER2", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "ApoER2 glycosylation status not directly assessed, but receptor is glycosylated.", "mechanism": "Loss of endothelial ApoER2 blunts skeletal muscle glucose disposal due to decreased insulin transport.", "protein": "ApoER2", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Glucose intolerance", "glycan_involvement": "ApoE3 is a glycoprotein; glycosylation may modulate receptor interaction.", "mechanism": "ApoE3 binding to ApoER2 enhances endothelial insulin uptake and transcytosis, promoting glucose disposal.", "protein": "ApoE3", "relationship_type": "protective", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "IQGAP1 is a glycoprotein; glycosylation may affect scaffolding function.", "mechanism": "IQGAP1 is required for ApoE3/ApoER2-induced insulin transcytosis; its absence impairs insulin delivery.", "protein": "IQGAP1", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "medium", "disease": "Glucose intolerance", "glycan_involvement": "Dab2 is a glycoprotein; glycosylation may affect adaptor function.", "mechanism": "Dab2 is required for ApoE3/ApoER2-mediated insulin uptake in endothelial cells.", "protein": "Dab2", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Obesity-related insulin resistance", "glycan_involvement": "Sialylation of IgG Fc glycan is critical; hyposialylation increases disease risk.", "mechanism": "Hyposialylated IgG interacts with Fc\u03b3RIIB, blunting endothelial insulin transport and causing insulin resistance.", "protein": "Fc\u03b3RIIB", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Altered Fc glycan sialylation is key to pathogenicity.", "mechanism": "IgG from diabetic subjects impairs endothelial insulin transport, causing insulin resistance.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "medium", "disease": "Glucose intolerance", "glycan_involvement": "ER\u03b1 is glycosylated; glycosylation may affect receptor function.", "mechanism": "Endothelial ER\u03b1 promotes insulin transport and glucose disposal; deficiency leads to intolerance.", "protein": "ER\u03b1", "relationship_type": "protective", "source_pmcid": "PMC12466289" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "IRS2 is glycosylated; glycosylation may affect signaling.", "mechanism": "Endothelial IRS2 deletion impairs insulin-induced capillary recruitment and muscle glucose disposal.", "protein": "IRS2", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Exocyst proteins are glycosylated; glycosylation may affect complex assembly.", "mechanism": "Exocyst complex is required for IQGAP1-mediated insulin exocytosis in endothelium; inhibition impairs insulin delivery.", "protein": "Exocyst complex proteins", "relationship_type": "causal", "source_pmcid": "PMC12466289" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "Reduced \u03b12,6-linked sialic acid on T cell surface N-glycans.", "mechanism": "Loss of ST6GAL1-mediated \u03b12,6-sialylation on T cells leads to reduced T cell responsiveness with age.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12467053" }, { "confidence": "high", "disease": "Infection (Listeria monocytogenes)", "glycan_involvement": "Loss of \u03b12,6-sialylation impairs T cell activation and proliferation.", "mechanism": "T cell-specific ST6GAL1 knockout mice show impaired CD8+ T cell response and poor infection control.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12467053" }, { "confidence": "high", "disease": "Cancer (tumor growth)", "glycan_involvement": "Reduced \u03b12,6-sialylation dampens anti-tumor T cell function.", "mechanism": "ST6GAL1-deficient T cells are less effective at controlling tumor growth; tumors grow faster.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12467053" }, { "confidence": "medium", "disease": "Reduced anti-tumor immunity", "glycan_involvement": "PD-1 is glycosylated; loss of \u03b12,6-sialylation may alter its function.", "mechanism": "PD-1 blockade partially restores anti-tumor function in ST6GAL1-deficient T cells.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467053" }, { "confidence": "medium", "disease": "Immunosenescence", "glycan_involvement": "N-glycosylation and possibly \u03b12,6-sialylation modulate CTLA-4.", "mechanism": "CTLA-4 function and surface retention are regulated by N-glycan branching, which is altered with age.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12467053" }, { "confidence": "high", "disease": "T cell exhaustion", "glycan_involvement": "Loss of \u03b12,6-sialylation on CD44+ T cells.", "mechanism": "CD44+ (activated) T cells lose \u03b12,6-sialylation, marking terminal differentiation and reduced function.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12467053" }, { "confidence": "medium", "disease": "Impaired T cell response", "glycan_involvement": "Desialylation exposes galactose on N-glycans.", "mechanism": "Loss of \u03b12,6-sialylation exposes galactose motifs, increasing galectin binding and suppressing T cell function.", "protein": "Galectins", "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC12467053" }, { "confidence": "high", "disease": "Age-related infection susceptibility", "glycan_involvement": "Reduced \u03b12,6-sialylation on CD8+ T cell N-glycans.", "mechanism": "CD8+ T cells lose \u03b12,6-sialylation with age, correlating with reduced infection control.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12467053" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Sialylation of antigens modulates CD4+ T cell differentiation.", "mechanism": "Sialylated antigens promote regulatory CD4+ T cells and suppress inflammatory responses.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective (hypothesized)", "source_pmcid": "PMC12467053" }, { "confidence": "medium", "disease": "Reduced vaccine efficacy", "glycan_involvement": "Reduced \u03b12,6-linked sialic acid on T cells.", "mechanism": "Loss of \u03b12,6-sialylation may impair T cell responsiveness to vaccination.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC12467053" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP trafficking and processing.", "mechanism": "APP is cleaved to produce amyloid-beta peptides, which aggregate to form plaques central to AD pathogenesis.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12467072" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates APOE structure and receptor interactions.", "mechanism": "APOE \u03b54 allele increases risk by impairing amyloid-beta clearance and modulating neuroinflammation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycosylation affects stability and function.", "mechanism": "CLU regulates cholesterol/lipid metabolism and is implicated in amyloid-beta aggregation and clearance.", "protein": "Clusterin (CLU)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Contains glycosylated domains affecting ligand binding.", "mechanism": "SORL1 binds APP and A\u03b2, reducing amyloidogenic processing and facilitating lysosomal degradation.", "protein": "SORL1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12467072" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated CSF YKL-40 reflects active neuroinflammation and neuronal damage in AD.", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates inhibitory activity and stability.", "mechanism": "Released by activated astroglia; may exacerbate or alleviate AD pathology.", "protein": "Alpha1-antichymotrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects protease trapping and clearance.", "mechanism": "Acute-phase reactant released by astroglia; involved in protease inhibition and amyloid clearance.", "protein": "Alpha2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for function and stability.", "mechanism": "CRP is an acute-phase reactant released during neuroinflammation in AD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects synaptic vesicle trafficking.", "mechanism": "Decreased SV2A interaction in hippocampus correlates with synaptic loss in AD.", "protein": "SV2A (Synaptic vesicle glycoprotein 2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12467072" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates cell surface expression and ligand binding.", "mechanism": "TREM2 variants increase AD risk by impairing microglial response and amyloid clearance.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12467072" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "N-glycosylation motifs present; may affect protein stability and activity.", "mechanism": "Mutations in BTD gene reduce or abolish biotinidase activity, impairing biotin recycling and leading to BD.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Glycosylation may modulate enzyme activity and stability.", "mechanism": "Pathogenic BTD variants (e.g., D444H, H323R, R209C) serve as genetic biomarkers for BD risk and carrier status.", "protein": "Biotinidase", "relationship_type": "biomarker", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Glycosylation status may influence therapeutic efficacy.", "mechanism": "Restoration of biotinidase activity via biotin supplementation reverses BD symptoms.", "protein": "Biotinidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Mutation may affect glycosylation site accessibility.", "mechanism": "D444H mutation causes mild structural deviation, correlating with milder BD phenotypes.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Mutations near glycosylation motifs may disrupt glycan-mediated stability.", "mechanism": "C186Y, R209C, Q456H, P497S mutations destabilize protein structure, impairing function and causing BD.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Potential impact on local glycosylation and enzyme activity.", "mechanism": "R209C mutation adjacent to YRK210\u2013212 motif disrupts catalytic K212 stabilization, leading to BD.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "medium", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "May influence glycosylation-dependent folding.", "mechanism": "H323R mutation alters domain-domain alignment, affecting enzyme stability and function.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "medium", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Possible effect on glycan-mediated conformational dynamics.", "mechanism": "Q456H mutation increases salt bridges, potentially rigidifying protein and impairing flexibility needed for catalysis.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "medium", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "May affect glycosylation site exposure.", "mechanism": "P497S mutation increases local mobility, destabilizing inter-domain packing and enzyme function.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "medium", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Distal from glycosylation motifs; minor impact expected.", "mechanism": "Q511E mutation alters tertiary structure stability, potentially impacting substrate binding and BD risk.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC12467526" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects antibody binding and affinity maturation.", "mechanism": "CD133 is a cancer stem cell marker targeted by mAbs for tumor cell elimination.", "protein": "CD133", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates epitope exposure and antibody specificity.", "mechanism": "EGFR overexpression in tumors is targeted by mAbs for selective tumor cell killing.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Autoimmune disorders", "glycan_involvement": "N-glycosylation patterns regulate effector functions and half-life.", "mechanism": "Fc glycosylation modulates ADCC, CDC, and immunogenicity in antibody therapies.", "protein": "Fc region of IgG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences mAb pharmacokinetics and immunogenicity.", "mechanism": "Humanized mAbs target A\u03b2 aggregates for clearance, reducing neurotoxicity.", "protein": "A\u03b2 protofibrils", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Autoimmune disorders", "glycan_involvement": "Fc glycosylation affects FcRn binding and antibody half-life.", "mechanism": "Blocking FcRn-IgG interaction accelerates IgG degradation, lowering pathogenic IgG.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect antigen recognition and antibody specificity.", "mechanism": "Anti-ROS1 mAbs neutralize oncogenic signaling in ROS1-positive tumors.", "protein": "ROS1", "protein_enriched": { "function": "Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous s", "gene_name": "ROS1", "glycan_count": 1, "glycosylation_sites_count": 30, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08922" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation impacts antibody binding and immune escape.", "mechanism": "mAbs target spike protein to neutralize virus and prevent infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "medium", "disease": "Pain", "glycan_involvement": "Glycosylation influences antibody-receptor interaction.", "mechanism": "mAbs modulate receptor activity for analgesic effects.", "protein": "Cholecystokinin B receptor", "protein_enriched": { "function": "Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor media", "gene_name": "CCKBR", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P32239" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "Glycosylation may affect antibody pharmacokinetics and immunogenicity.", "mechanism": "mAbs inhibit PCSK9 to lower LDL cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Fc glycosylation modulates effector function and clearance.", "mechanism": "Anti-TNF-\u03b1 mAbs neutralize inflammatory cytokine in autoimmune disease.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467787" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation may modulate aggregation and toxicity.", "mechanism": "PTAU181 accumulation promotes neurofibrillary tangle formation, leading to entorhinal cortex atrophy and cognitive decline.", "protein": "Phosphorylated Tau (PTAU181)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12467901" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "O-glycosylation may affect tau clearance and aggregation.", "mechanism": "PTAU181 levels in CSF/plasma predict AD progression and correlate with neurodegeneration.", "protein": "Phosphorylated Tau (PTAU181)", "relationship_type": "biomarker", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Subarachnoid Hemorrhage", "glycan_involvement": "N-glycosylation critical for iron binding and immune modulation.", "mechanism": "Lactoferrin binds iron, facilitates efferocytosis of apoptotic RBCs, and reduces iron toxicity.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation required for ligand binding and receptor stability.", "mechanism": "CD163 mediates hemoglobin scavenging by microglia, reducing heme toxicity and neuroinflammation.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "CD36 enhances microglial erythrophagocytosis, promoting clearance of RBCs and reducing neurotoxicity.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Ferroptosis (cell death)", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "GPX4 detoxifies lipid hydroperoxides, preventing iron-dependent cell death in entorhinal cortex astrocytes.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation influences iron storage and release.", "mechanism": "Ferritin stores iron; dysregulation leads to iron overload, oxidative stress, and neurodegeneration.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation affects membrane localization and function.", "mechanism": "FPN1 exports iron; dysfunction causes intracellular iron accumulation and ROS production.", "protein": "Ferroportin (FPN1)", "protein_enriched": { "function": "Transports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis (PubMed:15692071, PubMed:22178646, PubMed:22682227, PubMed:24304836", "gene_name": "SLC40A1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP59" }, "relationship_type": "causal", "source_pmcid": "PMC12467901" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may regulate enzyme activity.", "mechanism": "HO-1 in microglia detoxifies heme from RBC breakdown, reducing oxidative stress.", "protein": "Heme Oxygenase-1 (HO-1)", "relationship_type": "protective", "source_pmcid": "PMC12467901" }, { "confidence": "low", "disease": "Ferroptosis (cell death)", "glycan_involvement": "Glycosylation may affect enzyme function.", "mechanism": "SAT1 expression in EC astrocytes increases susceptibility to iron-driven lipid peroxidation and cell death.", "protein": "SAT1", "protein_enriched": { "function": "Enzyme which catalyzes the acetylation of polyamines (PubMed:15283699, PubMed:16455797, PubMed:17516632). Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine (PubMed:17", "gene_name": "SAT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P21673" }, "relationship_type": "causal", "source_pmcid": "PMC12467901" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation of APP affects its trafficking and cleavage.", "mechanism": "Aberrant processing of glycosylated APP leads to amyloid-\u03b2 accumulation and plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12467958" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau phosphorylation and aggregation.", "mechanism": "Hyperphosphorylation and aggregation of tau, a glycoprotein, form neurofibrillary tangles.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation is critical for PrPC folding and function.", "mechanism": "Misfolded or oxidatively modified PrPC loses neuroprotective function and exacerbates amyloid-\u03b2 toxicity.", "protein": "Cellular prion protein (PrPC)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects SOD secretion and stability.", "mechanism": "SOD detoxifies superoxide radicals; reduced activity in AD increases oxidative stress.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences CAT localization and activity.", "mechanism": "CAT breaks down hydrogen peroxide; decreased activity in AD contributes to oxidative damage.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates GPx secretion and function.", "mechanism": "GPx reduces peroxides; lower levels in AD increase vulnerability to oxidative stress.", "protein": "Glutathione peroxidase (GPx)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles", "gene_name": "Gsta4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24472" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect\u2014regulates glycoprotein antioxidants.", "mechanism": "Nrf2 regulates expression of antioxidant glycoproteins; impaired activation in AD increases oxidative stress.", "protein": "Nrf2 (NFE2L2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects HO-1 stability and activity.", "mechanism": "HO-1 expression is induced by oxidative stress; upregulation is neuroprotective.", "protein": "Heme oxygenase-1 (HO-1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "NQO1 detoxifies quinones and reduces oxidative stress; regulated by Nrf2.", "protein": "Quinone oxidoreductase (NQO1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12467958" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation is essential for LRP1 trafficking and ligand binding.", "mechanism": "LRP1 mediates clearance of amyloid-\u03b2 across the blood\u2013brain barrier; upregulation improves A\u03b2 removal.", "protein": "Low-density lipoprotein receptor-related protein 1 (LRP1)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12467958" }, { "confidence": "high", "disease": "Cardiomyopathy in DMD", "glycan_involvement": "Pro-BNP is a glycoprotein; glycosylation affects its stability and clearance, influencing its biomarker utility.", "mechanism": "Pro-BNP is released in response to ventricular stress and dysfunction, reflecting subclinical or overt cardiac involvement in DMD.", "protein": "Pro-BNP (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12468195" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation of Pro-BNP modulates its plasma half-life and immunoreactivity.", "mechanism": "Elevated Pro-BNP indicates increased cardiac wall stress and is used to assess heart failure severity.", "protein": "Pro-BNP (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12468195" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may affect assay detection and circulating levels.", "mechanism": "Used to detect subclinical cardiac involvement in DMD patients.", "protein": "Pro-BNP (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12468195" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "Glycosylation of TIM-3 modulates immune checkpoint function and antibody accessibility.", "mechanism": "Molecular mimicry with SARS-CoV-2 S protein may trigger autoantibodies against TIM-3, disrupting immune tolerance.", "protein": "HAVR2/TIM-3", "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Immunologic tolerance breakdown", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and immune interactions.", "mechanism": "Cross-reactive antibodies may impair FSTL1's immunomodulatory role, promoting autoimmunity.", "protein": "FSTL1", "protein_enriched": { "function": "Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation (PubMed:22265692, PubMed:2921", "gene_name": "FSTL1", "glycan_count": 27, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G49108TO", "G05724UK", "G25451PN", "G27058EU", "G31852PQ", "G41247ZX", "G45395BF", "G46503DX", "G60177UT", "G62765YT", "G64527OM", "G70101JE", "G70375MX", "G78790NZ", "G80920RR", "G83460ZZ", "G84452RH", "G90659AW", "G05962QB", "G11101UV", "G13193DT", "G39471UU", "G69521XL", "G12270AG" ], "uniprot_id": "Q12841" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Muscle dysfunction/post-exertional malaise", "glycan_involvement": "Glycosylation mediates matrix interactions and immune recognition.", "mechanism": "Autoantibodies may disrupt EMILIN3's role in TGF-\u03b2 signaling and extracellular matrix, contributing to muscle symptoms post-COVID.", "protein": "EMILIN3", "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "Heavily glycosylated; glycan chains regulate lysosomal trafficking and immune accessibility.", "mechanism": "Autoantibodies may alter lysosomal function and antigen presentation, affecting immune activation.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "protective/causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Respiratory distress in COVID-19", "glycan_involvement": "Glycosylation affects channel function and surface expression.", "mechanism": "Autoantibodies against \u03b1ENaC may impair sodium transport, contributing to pulmonary edema and loss of taste.", "protein": "\u03b1ENaC (SCNN1A)", "protein_enriched": { "function": "This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis (PubMed:30251954, PubMed:32729833, P", "gene_name": "SCNN1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P37088" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Neurological manifestations of COVID-19", "glycan_involvement": "Potential glycosylation may affect extracellular localization and immune recognition.", "mechanism": "Autoantibodies may disrupt DAAM2's role in myelin structure and oligodendrocyte function, contributing to neuroinflammation.", "protein": "DAAM2", "protein_enriched": { "function": "Receptor component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions", "gene_name": "HEG1", "glycan_count": 32, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G71142DF", "G22310AV", "G48414YA", "G56784JY", "G75983OB", "G80920RR", "G10019LZ", "G23010ZW", "G31665QC", "G33791AF", "G38663NM", "G52527GH", "G57888GL", "G82463GQ", "G84452RH", "G86500WE", "G62765YT", "G57321FI", "G43417UB", "G25079LO", "G29068FM", "G08290VR", "G64394MX", "G06356OH", "G47950XN", "G88779RV", "G86795LJ", "G47518TP", "G29931IJ", "G53434XO", "G57317CE", "G49108TO" ], "uniprot_id": "Q9ULI3" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Neurological manifestations of COVID-19", "glycan_involvement": "Glycosylation critical for cell adhesion and immune recognition.", "mechanism": "Autoantibodies may impair CHL1-mediated synaptic plasticity and neuronal survival.", "protein": "CHL1", "protein_enriched": { "function": "Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of ", "gene_name": "PPP1R12A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14974" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "low", "disease": "Cardiac involvement in COVID-19", "glycan_involvement": "Not specified; possible indirect effects via immune recognition.", "mechanism": "Autoantibodies may affect FHOD3's actin assembly in cardiomyocytes, contributing to cardiac symptoms.", "protein": "FHOD3", "protein_enriched": { "function": "Actin-organizing protein that may cause stress fiber formation together with cell elongation (By similarity). Isoform 4 may play a role in actin filament polymerization in cardiomyocytes", "gene_name": "FHOD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q2V2M9" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "low", "disease": "Immune-related adverse events (cancer immunotherapy)", "glycan_involvement": "Not specified; possible indirect effects.", "mechanism": "Autoantibodies may disrupt MYO18A's role in macrophage and B-cell homeostasis, exacerbating immune dysregulation.", "protein": "MYO18A", "protein_enriched": { "function": "Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the sp", "gene_name": "HNRNPH3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P31942" }, "relationship_type": "causal", "source_pmcid": "PMC12469275" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates immune checkpoint function.", "mechanism": "HLA-DRB1*04:01/04:05 alleles associated with increased risk; molecular mimicry may trigger anti-TIM-3 autoimmunity.", "protein": "HAVR2/TIM-3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12469275" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin complex interacts with glycosylated proteins (e.g., dystroglycan); glycosylation is critical for complex stability.", "mechanism": "Loss-of-function mutations in DMD gene cause absence of dystrophin, leading to muscle fiber instability and degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "Sarcoglycanopathies (LGMDR3)", "glycan_involvement": "Sarcoglycans are glycosylated; glycosylation is important for membrane localization and complex formation.", "mechanism": "Mutations in SGCA gene cause loss/reduction of \u03b1-sarcoglycan at sarcolemma, leading to muscle degeneration.", "protein": "\u03b1-Sarcoglycan (SGCA)", "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "Sarcoglycanopathies (LGMDR4)", "glycan_involvement": "Glycosylation required for proper trafficking and function.", "mechanism": "SGCB mutations result in \u03b2-sarcoglycan deficiency, disrupting sarcoglycan complex and muscle membrane integrity.", "protein": "\u03b2-Sarcoglycan (SGCB)", "protein_enriched": { "function": "Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes me", "gene_name": "AP3B1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00203" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "Sarcoglycanopathies (LGMDR5)", "glycan_involvement": "Glycosylation affects complex assembly.", "mechanism": "SGCG mutations cause \u03b3-sarcoglycan loss, leading to sarcolemma instability.", "protein": "\u03b3-Sarcoglycan (SGCG)", "protein_enriched": { "function": "Transcription factor that plays a key role in cardiovascular development by promoting pharyngeal arch segmentation during embryonic development (By similarity). Also involved in craniofacial muscle de", "gene_name": "TBX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43435" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "Sarcoglycanopathies (LGMDR6)", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "SGCD mutations cause \u03b4-sarcoglycan deficiency, resulting in muscle pathology.", "protein": "\u03b4-Sarcoglycan (SGCD)", "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "LGMDR9", "glycan_involvement": "FKRP is a glycosyltransferase; mutations disrupt O-glycosylation of \u03b1-dystroglycan and sialylation of fibronectin.", "mechanism": "FKRP mutations impair glycosylation of muscle proteins, leading to muscular dystrophy.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "LGMDR19", "glycan_involvement": "Essential for O-mannosyl glycosylation of \u03b1-dystroglycan.", "mechanism": "GMPPB mutations impair glycosylation of \u03b1-dystroglycan, causing muscle weakness.", "protein": "GMPPB", "protein_enriched": { "function": "Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, diff", "gene_name": "DDR1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q08345" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "medium", "disease": "Dysferlinopathy (LGMDR2)", "glycan_involvement": "Dysferlin is a glycoprotein; glycosylation may affect membrane targeting.", "mechanism": "DYSF mutations cause dysferlin deficiency, impairing sarcolemma repair.", "protein": "Dysferlin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "medium", "disease": "Brody Myopathy (BM)", "glycan_involvement": "SERCA1 is glycosylated; glycosylation may affect stability and function.", "mechanism": "ATP2A1 mutations reduce SERCA1 function, impairing Ca2+ reuptake and muscle relaxation.", "protein": "SERCA1 (ATP2A1)", "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "LGMDR9", "glycan_involvement": "O-glycosylation (sialylation) of fibronectin is disrupted.", "mechanism": "FKRP mutations reduce sialylation of fibronectin, impairing fibronectin\u2013collagen binding and muscle basement membrane integrity.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12469501" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with O-mannosylated dystroglycan; glycosylation is critical for DAPC function.", "mechanism": "Loss-of-function mutations in dystrophin disrupt muscle membrane integrity, leading to DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12469774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DAPC contains glycoproteins; dystroglycan glycosylation is essential for ECM binding.", "mechanism": "Disruption of DAPC (including glycoprotein dystroglycan) impairs muscle stability and signaling.", "protein": "DAPC (Dystrophin-associated protein complex)", "relationship_type": "causal", "source_pmcid": "PMC12469774" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation of dystroglycan is critical for function; hypoglycosylation exacerbates disease.", "mechanism": "Defective glycosylation of dystroglycan impairs DAPC-ECM interaction, contributing to DMD pathology.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12469774" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "VDAC is N-glycosylated, which may affect channel function and drug interaction.", "mechanism": "VDAC mediates mitochondrial calcium overload; inhibition by VBIT-4 reduces muscle degeneration in severe DMD.", "protein": "VDAC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation is required for GRP78 folding and function.", "mechanism": "GRP78 is upregulated as a marker of ER stress in dystrophin-deficient muscle.", "protein": "GRP78", "relationship_type": "biomarker", "source_pmcid": "PMC12469774" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "N-glycosylation may modulate VDAC function in neurodegeneration.", "mechanism": "VDAC inhibition by VBIT-4 shows therapeutic effects in AD models.", "protein": "VDAC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "low", "disease": "Lupus", "glycan_involvement": "N-glycosylation may influence VDAC immune signaling.", "mechanism": "VDAC inhibition by VBIT-4 ameliorates lupus symptoms in models.", "protein": "VDAC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "N-glycosylation may affect VDAC\u2019s metabolic role.", "mechanism": "VDAC inhibition by VBIT-4 improves mitochondrial function in diabetes models.", "protein": "VDAC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "low", "disease": "Cardiac fibrosis", "glycan_involvement": "N-glycosylation may modulate VDAC\u2019s role in cardiac cells.", "mechanism": "VDAC inhibition by VBIT-4 reduces cardiac fibrosis in animal models.", "protein": "VDAC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation is essential for GRP78\u2019s ER localization and function.", "mechanism": "Reduction of GRP78 by VBIT-4 indicates mitigation of ER stress in severe DMD.", "protein": "GRP78", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12469774" }, { "confidence": "high", "disease": "Peritoneal metastasis of gastric cancer", "glycan_involvement": "Binds sulfated and fucosylated glycans on cell surface glycoproteins.", "mechanism": "Galectin-4 promotes peritoneal dissemination by stabilizing lipid rafts and glycoproteins on gastric cancer cells.", "protein": "Galectin-4", "relationship_type": "causal", "source_pmcid": "PMC12470716" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Targeting galectin-4-glycan interactions with sulfated/fucosylated glycans.", "mechanism": "Inhibition of galectin-4 (by fucoidan analogs) suppresses proliferation and metastasis of galectin-4-positive gastric cancer cells.", "protein": "Galectin-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12470716" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Recognizes specific glycan motifs on glycoproteins.", "mechanism": "Galectin-4 expression correlates with malignant transformation and metastatic potential.", "protein": "Galectin-4", "relationship_type": "biomarker", "source_pmcid": "PMC12470716" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "c-MET is a glycoprotein; its cell surface retention is regulated by galectin-4-glycan lattices.", "mechanism": "c-MET signaling promotes proliferation; galectin-4 stabilizes c-MET on the cell surface.", "protein": "c-MET", "relationship_type": "causal", "source_pmcid": "PMC12470716" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Inhibition of galectin-4-glycan interactions.", "mechanism": "Fucoidan inhibits proliferation of galectin-4-expressing colorectal cancer cells.", "protein": "Galectin-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12470716" }, { "confidence": "low", "disease": "Gastric cancer", "glycan_involvement": "Binds \u03b2-galactoside glycans on glycoproteins.", "mechanism": "Galectin-3 is expressed in gastric cancer cells but not correlated with peritoneal dissemination.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12470716" }, { "confidence": "high", "disease": "Peritoneal metastasis of gastric cancer", "glycan_involvement": "Synthetic sulfated/fucosylated glycans block galectin-4 binding.", "mechanism": "Fucoidan analogs inhibit galectin-4, reducing peritoneal metastasis.", "protein": "Galectin-4", "relationship_type": "protective", "source_pmcid": "PMC12470716" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Multivalent glycan presentation increases galectin-4 inhibition.", "mechanism": "Cholestanol-conjugated fucoidan analogs (e.g., analog 14) show enhanced inhibition of galectin-4 and cancer cell proliferation.", "protein": "Galectin-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12470716" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Requires specific glycan motifs (sulfated/fucosylated) on glycoproteins.", "mechanism": "Galectin-4 cross-links glycoproteins, forming lattices that regulate signaling and promote tumor progression.", "protein": "Galectin-4", "relationship_type": "causal", "source_pmcid": "PMC12470716" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "c-MET glycosylation may affect galectin-4-mediated stabilization.", "mechanism": "Downregulation of c-MET/pMET by galectin-4 inhibition (fucoidan analogs) suppresses cancer cell proliferation.", "protein": "c-MET", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12470716" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation affects APP trafficking and processing.", "mechanism": "APP undergoes amyloidogenic processing to generate A\u03b2 peptides, which aggregate and drive AD pathology.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation modulates BACE1 stability and localization.", "mechanism": "BACE1 initiates amyloidogenic cleavage of APP, increasing A\u03b2 production; inhibition reduces AD pathology.", "protein": "Beta-site APP cleaving enzyme 1 (BACE1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation influences \u03b3-secretase complex assembly.", "mechanism": "Presenilin-1 is the catalytic subunit of \u03b3-secretase, generating A\u03b2 peptides; mutations increase A\u03b242 production.", "protein": "Presenilin-1", "relationship_type": "causal", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "O-glycosylation may modulate tau aggregation propensity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, destabilizing microtubules and impairing neuronal function.", "protein": "Tau (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Traumatic Brain Injury (TBI)", "glycan_involvement": "N-glycosylation impacts APP axonal transport after injury.", "mechanism": "APP upregulation and A\u03b2 accumulation occur rapidly post-TBI, mirroring AD-like changes.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC12471116" }, { "confidence": "medium", "disease": "Chronic Traumatic Encephalopathy (CTE)", "glycan_involvement": "O-glycosylation may affect tau aggregation in CTE.", "mechanism": "Repetitive TBI induces tau hyperphosphorylation and aggregation, leading to CTE.", "protein": "Tau (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12471116" }, { "confidence": "medium", "disease": "Traumatic Brain Injury (TBI)", "glycan_involvement": "Polysialylation of NCAM1 modulates cell adhesion and plasticity post-injury.", "mechanism": "NCAM1 genetic variants are associated with TBI risk and outcomes.", "protein": "Neural cell adhesion molecule 1 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation affects APOE isoform function and A\u03b2 clearance.", "mechanism": "APOE4 genotype increases risk and severity of AD and worsens calcium-driven pathology.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC12471116" }, { "confidence": "medium", "disease": "Traumatic Brain Injury (TBI)", "glycan_involvement": "Glycosylation may influence spectrin stability and proteolysis.", "mechanism": "Calpain-mediated spectrin breakdown (SBDP145) is a marker of axonal injury in TBI and AD.", "protein": "Spectrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12471116" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation may regulate PSD-95 localization and interactions.", "mechanism": "Calpain cleavage of PSD-95 disrupts synaptic architecture, correlating with cognitive decline.", "protein": "PSD-95 (DLG4)", "protein_enriched": { "function": "Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts wi", "gene_name": "DLG4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P78352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12471116" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation affects immune modulation and acute phase response", "mechanism": "Elevated plasma levels in PDAC, associated with poor survival", "protein": "Alpha-1-acid glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation may affect stability and immune recognition", "mechanism": "Elevated plasma levels in PDAC, associated with poor survival", "protein": "Beta-2-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation modulates inhibitor activity and half-life", "mechanism": "Elevated plasma levels in PDAC, associated with poor survival", "protein": "Plasma protease C1 inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation influences secretion and immune interactions", "mechanism": "Elevated plasma levels in PDAC, associated with poor survival", "protein": "Leucine-rich alpha-2-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation affects cell adhesion and ECM interactions", "mechanism": "Lower plasma levels associated with poor survival in PDAC", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation modulates enzyme stability and clearance", "mechanism": "Lower plasma levels associated with poor survival in PDAC", "protein": "Cholinesterase", "protein_enriched": { "function": "Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters", "gene_name": "BCHE", "glycan_count": 40, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G00912UN", "G01650EU", "G11314AS", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G37881RL", "G40574BA", "G41247ZX", "G59626AS", "G62765YT", "G80920RR", "G83646BJ", "G86795LJ", "G95865ZB", "G43089EG", "G70441OD", "G08918WF", "G27058EU", "G43223CG", "G11629QQ", "G12270AG", "G13694XX", "G15169WU", "G48414YA", "G55412XP", "G62461SM", "G81263BG", "G84452RH", "G28465XX", "G06247RL", "G27947YN", "G42466VF", "G45395BF", "G70232NH", "G70619PT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P06276" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects inhibitor function", "mechanism": "Altered plasma levels associated with disease risk", "protein": "Plasma protease C1 inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation affects inhibitor function", "mechanism": "Altered plasma levels associated with disease risk", "protein": "Plasma protease C1 inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Renal disease", "glycan_involvement": "N-glycosylation may affect clearance", "mechanism": "Elevated plasma levels in renal dysfunction", "protein": "Beta-2-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "medium", "disease": "Hematological malignancies", "glycan_involvement": "N-glycosylation may affect immune recognition", "mechanism": "Elevated plasma levels in various blood cancers", "protein": "Beta-2-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12471192" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects TREM2 stability and ligand binding.", "mechanism": "Regulates microglial phagocytosis and clustering around A\u03b2 plaques; loss impairs A\u03b2 clearance and increases tau pathology.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates receptor function and ligand interaction.", "mechanism": "Mediates microglial uptake of A\u03b2; chronic activation leads to neuroinflammation and neurotoxicity.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for proper folding and cell surface expression.", "mechanism": "Facilitates microglial uptake and lysosomal degradation of A\u03b2; loss accelerates plaque deposition.", "protein": "SR-AI/II (SCARA1)", "protein_enriched": { "function": "", "gene_name": "MRPS7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2R9" }, "relationship_type": "protective", "source_pmcid": "PMC12471207" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences receptor trafficking and function.", "mechanism": "May facilitate A\u03b2 efflux across BBB and modulate lipid metabolism.", "protein": "SR-BI (SCARB1)", "relationship_type": "protective", "source_pmcid": "PMC12471207" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ligand binding and anti-inflammatory signaling.", "mechanism": "Upregulated in neuroinflammatory conditions; marks anti-inflammatory microglia/macrophages.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates ligand specificity and signaling.", "mechanism": "Facilitates A\u03b2 influx into brain and triggers pro-inflammatory signaling.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for receptor function and trafficking.", "mechanism": "Mediates A\u03b2 uptake and efflux; loss impairs clearance and increases inflammation.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "Highly glycosylated; glycans mediate immune evasion and receptor interactions.", "mechanism": "Disrupts microglial lysosomal function and suppresses A\u03b2 clearance.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APP processing and trafficking.", "mechanism": "Source of A\u03b2 peptides; HIV Tat enhances APP cleavage and A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences receptor binding and lipid transport.", "mechanism": "Modulates A\u03b2 clearance via LRP1; ApoE4 allele increases AD risk.", "protein": "ApoE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12471207" }, { "confidence": "high", "disease": "Pseudorabies", "glycan_involvement": "gB is a glycoprotein; glycosylation is essential for receptor binding and fusion.", "mechanism": "gB mediates viral entry by binding host cell receptors and triggering membrane fusion.", "protein": "PRV glycoprotein gB", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY9" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "high", "disease": "Pseudorabies", "glycan_involvement": "gD is glycosylated; glycosylation facilitates receptor interaction.", "mechanism": "gD interacts with host THBS3 to promote viral attachment, fusion, and entry.", "protein": "PRV glycoprotein gD", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY8" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "high", "disease": "Pseudorabies", "glycan_involvement": "No direct glycosylation involvement; Drebrin modulates glycoprotein trafficking.", "mechanism": "Drebrin regulates actin cytoskeleton, affecting PRV internalization and replication.", "protein": "Drebrin", "protein_enriched": { "function": "Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment", "gene_name": "DBN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16643" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472004" }, { "confidence": "high", "disease": "Pseudorabies", "glycan_involvement": "Glycosaminoglycan chains are critical for virus binding.", "mechanism": "Serve as host cell receptors for PRV gB, mediating viral entry.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Pseudorabies", "glycan_involvement": "THBS3 is glycosylated; glycosylation may affect interaction with viral glycoproteins.", "mechanism": "THBS3 interacts with PRV gD to facilitate viral entry.", "protein": "THBS3", "protein_enriched": { "function": "RNA-binding protein that associates with the RNA exosome complex. Involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA and play a role in recruiting the RNA exosome complex to pre-r", "gene_name": "MPHOSPH6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99547" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Central nervous system diseases", "glycan_involvement": "Glycosylation of gB is required for neurotropism.", "mechanism": "PRV gB-mediated entry contributes to neuroinvasion and CNS pathology.", "protein": "PRV glycoprotein gB", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY9" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Endophthalmitis", "glycan_involvement": "Glycosylation supports tissue tropism.", "mechanism": "PRV gB enables viral entry into ocular tissues.", "protein": "PRV glycoprotein gB", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY9" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation is necessary for efficient CNS infection.", "mechanism": "gB-mediated entry leads to infection of brain cells.", "protein": "PRV glycoprotein gB", "protein_enriched": { "function": "", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJY9" }, "relationship_type": "causal", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Pseudorabies", "glycan_involvement": "No direct glycosylation; Drebrin affects glycoprotein trafficking.", "mechanism": "PRV infection upregulates Drebrin expression in host cells.", "protein": "Drebrin", "protein_enriched": { "function": "Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment", "gene_name": "DBN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16643" }, "relationship_type": "biomarker", "source_pmcid": "PMC12472004" }, { "confidence": "medium", "disease": "Pseudorabies", "glycan_involvement": "Indirect; Drebrin modulates actin-dependent trafficking of viral glycoproteins.", "mechanism": "Drebrin depletion impairs PRV replication, suggesting a host defense role.", "protein": "Drebrin", "protein_enriched": { "function": "Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment", "gene_name": "DBN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16643" }, "relationship_type": "protective", "source_pmcid": "PMC12472004" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma", "glycan_involvement": "EGFR is a glycoprotein; glycosylation not critical for NIR-PIT efficacy.", "mechanism": "EGFR is overexpressed in HNSCC; targeted by NIR-PIT with cetuximab-IR700, causing selective necrotic cell death.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "HER2 is a glycoprotein; glycosylation not critical for NIR-PIT efficacy.", "mechanism": "HER2 is overexpressed in breast cancer; NIR-PIT with trastuzumab-IR700 induces tumor cell death.", "protein": "HER2 (ErbB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Heavily N-glycosylated; antibodies recognize glycosylated epitopes.", "mechanism": "CD133 is a cancer stem cell marker in glioblastoma; NIR-PIT with AC133-IR700 suppresses tumor growth.", "protein": "CD133", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosaminoglycan modification increases molecular weight; not essential for NIR-PIT.", "mechanism": "CD44 variants are overexpressed in colorectal cancer; NIR-PIT induces immunogenic cell death.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Heavily glycosylated; glycosylation not essential for NIR-PIT.", "mechanism": "CEA is overexpressed in colorectal cancer; targeted by NIR-PIT and used as a serum biomarker.", "protein": "CEA", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation required for proteolytic activity; not essential for NIR-PIT.", "mechanism": "PSMA is highly expressed in prostate cancer; NIR-PIT targeting PSMA suppresses tumor proliferation.", "protein": "PSMA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Malignant pleural mesothelioma", "glycan_involvement": "Recognized by glycopeptide-specific antibodies; O-glycosylation present.", "mechanism": "PDPN is expressed in mesothelioma; NIR-PIT with NZ-1 antibody induces cancer cell death.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "Contains N-glycosylation sites; not essential for NIR-PIT.", "mechanism": "ICAM-1 is overexpressed in TNBC; NIR-PIT induces rapid cytoplasmic vacuolation and tumor suppression.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Glycoprotein; glycosylation not discussed as critical.", "mechanism": "Nectin-4 is overexpressed in bladder cancer; NIR-PIT with enfortumab biosimilars is effective.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosaminoglycan modification; not essential for NIR-PIT.", "mechanism": "CD44 targeted by H4C4 antibody reduces tumor growth and metastasis; NIR-PIT effective.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12472690" }, { "confidence": "high", "disease": "Dengue Fever (DF)", "glycan_involvement": "NS1 N-glycosylation affects immune recognition and antibody binding.", "mechanism": "Anti-NS1 antibodies mediate Fc-dependent effector functions (ADCC, ADCP, CDC) that protect against DENV infection.", "protein": "NS1 (Non-structural protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12474220" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Glycosylation at N130 and N207 modulates NS1 secretion and pathogenicity.", "mechanism": "NS1 induces vascular leakage and immune evasion, contributing to severe dengue.", "protein": "NS1 (Non-structural protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474220" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may affect NS1 immunogenicity and autoantibody generation.", "mechanism": "NS1-induced autoantibodies cross-react with platelet antigens, leading to platelet destruction.", "protein": "NS1 (Non-structural protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474220" }, { "confidence": "high", "disease": "Vascular leakage", "glycan_involvement": "Glycosylation influences NS1's interaction with endothelium.", "mechanism": "NS1 directly disrupts endothelial barrier and induces pro-inflammatory mediators.", "protein": "NS1 (Non-structural protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474220" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Afucosylation at N297 increases Fc\u03b3RIIIA binding and ADCC.", "mechanism": "High levels of afucosylated anti-NS1 IgG1 correlate with severe dengue and enhanced Fc\u03b3RIIIA-mediated inflammation.", "protein": "IgG1 (afucosylated, anti-NS1)", "relationship_type": "biomarker", "source_pmcid": "PMC12474220" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Afucosylation enhances Fc\u03b3RIIIA-mediated cytotoxicity.", "mechanism": "Afucosylated IgG1 immune complexes overactivate effector cells, reducing platelet counts.", "protein": "IgG1 (afucosylated, anti-NS1)", "relationship_type": "causal", "source_pmcid": "PMC12474220" }, { "confidence": "medium", "disease": "Dengue Fever (DF)", "glycan_involvement": "IgG3 glycosylation supports complement activation.", "mechanism": "Anti-NS1 IgG3 is associated with milder disease and efficient complement activation.", "protein": "IgG3 (anti-NS1)", "relationship_type": "protective", "source_pmcid": "PMC12474220" }, { "confidence": "medium", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Subclass and glycan profile modulate Fc effector function.", "mechanism": "Elevated anti-NS1 IgG1 levels are found in acute/past DHF, linked to increased inflammation.", "protein": "IgG1 (anti-NS1)", "relationship_type": "biomarker", "source_pmcid": "PMC12474220" }, { "confidence": "medium", "disease": "Dengue Shock Syndrome (DSS)", "glycan_involvement": "N-glycosylation affects NS1's pathogenic potential.", "mechanism": "NS1-induced vascular leakage and immune activation contribute to DSS.", "protein": "NS1 (Non-structural protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474220" }, { "confidence": "medium", "disease": "Dengue Fever (DF) in infants", "glycan_involvement": "Afucosylation enhances Fc\u03b3RIIIA binding, influencing disease susceptibility.", "mechanism": "Maternal afucosylated anti-NS1 IgG1 increases risk of symptomatic dengue in infants.", "protein": "IgG1 (afucosylated, anti-NS1)", "relationship_type": "biomarker", "source_pmcid": "PMC12474220" }, { "confidence": "high", "disease": "Gastroenteritis", "glycan_involvement": "Direct recognition of host sialylated glycans (\u03b12,3/\u03b12,6 SA) is essential for viral attachment.", "mechanism": "HA binds to sialic acid (SA) receptors (\u03b12,3 and \u03b12,6 linkages) on GI epithelial cells, mediating viral entry and direct GI infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Binding to colonic \u03b12,3/\u03b12,6 sialylated glycans.", "mechanism": "HA-mediated entry into colonic epithelial cells via SA receptors leads to inflammation and ulceration.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Appendicitis", "glycan_involvement": "Likely involves HA-SA interaction on GI mucosa.", "mechanism": "Direct or immune-mediated GI infection by influenza A (H1N1) associated with appendicitis.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Gastroenteritis", "glycan_involvement": "Recognition and cleavage of 9-O-acetylated sialic acids.", "mechanism": "HEF binds to N-acetyl-9-O-acetylneuraminic acid (9-O-Ac SA) on GI cells, mediating ICV entry and GI symptoms.", "protein": "Hemagglutinin-Esterase-Fusion (HEF)", "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Gastroenteritis", "glycan_involvement": "Cleavage of sialylated glycans on host cells.", "mechanism": "NA cleaves sialic acids, facilitating viral release and spread in GI tract.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Opportunistic GI infections", "glycan_involvement": "Initial viral entry via sialylated glycans.", "mechanism": "HA-mediated influenza infection disrupts GI immunity, predisposing to secondary bacterial infections.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Gut microbiome dysbiosis", "glycan_involvement": "Indirect; initial infection via glycan binding.", "mechanism": "Influenza infection alters gut microbiota composition via immune and epithelial disruption.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Gastroenteritis", "glycan_involvement": "Attachment to host glycosaminoglycans (HSPGs).", "mechanism": "RSV G protein binds to heparan sulfate proteoglycans (HSPGs) and CX3CR1, facilitating GI infiltration.", "protein": "Glycoprotein G (RSV)", "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "high", "disease": "Gastroenteritis", "glycan_involvement": "Recognition of SA-rich glycans and ACE2 glycoprotein.", "mechanism": "Spike protein binds to ACE2 and sialylated glycoproteins on GI epithelial cells, mediating entry.", "protein": "Spike (S) protein (SARS-CoV-2)", "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "medium", "disease": "Hemorrhagic gastritis", "glycan_involvement": "Binding to sialylated glycans on gastric epithelial cells.", "mechanism": "Direct infection of gastric mucosa via HA-SA interaction leads to mucosal damage and bleeding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474308" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Envelope glycoprotein likely glycosylated, facilitating fusion and immune recognition", "mechanism": "Gc mediates membrane fusion and viral entry into host cells", "protein": "SBV Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Envelope glycoprotein likely glycosylated, involved in receptor binding", "mechanism": "Gn mediates viral attachment to host cell receptors", "protein": "SBV Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12474314" }, { "confidence": "medium", "disease": "Arthrogryposis-hydranencephaly syndrome", "glycan_involvement": "Glycosylation may affect tropism and immune evasion", "mechanism": "Gc enables SBV infection of fetal tissues, leading to congenital malformations", "protein": "SBV Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12474314" }, { "confidence": "medium", "disease": "Abortion/stillbirth in ruminants", "glycan_involvement": "Glycosylation may modulate immune response and pathogenicity", "mechanism": "Gc-mediated infection disrupts fetal development", "protein": "SBV Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation influences antigenicity and antibody recognition", "mechanism": "Gc is the major antigen for neutralizing antibody detection and serological surveillance", "protein": "SBV Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation may affect immunogenicity and vaccine efficacy", "mechanism": "Gc is the primary target for vaccine development", "protein": "SBV Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12474314" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation may influence receptor binding and immune evasion", "mechanism": "Gn is a potential target for blocking viral attachment", "protein": "SBV Gn glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation of precursor and products is critical for function", "mechanism": "GPC is cleaved to produce Gn and Gc, both essential for viral infectivity", "protein": "SBV GPC (glycoprotein precursor)", "relationship_type": "causal", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation modulates antibody binding and protective efficacy", "mechanism": "Neutralizing antibodies against Gc confer protection", "protein": "SBV Gc glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12474314" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycan shield reduces antibody accessibility", "mechanism": "Gc glycosylation may help SBV evade host immune responses", "protein": "SBV Gc glycoprotein", "relationship_type": "immune_evasion", "source_pmcid": "PMC12474314" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CLEC5A recognizes viral glycans on spike protein.", "mechanism": "CLEC5A upregulation on monocytes correlates with inflammatory response and disease severity.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "biomarker", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "Vaccine-induced immunity", "glycan_involvement": "CLEC5A binds spike glycoprotein glycans, facilitating APC differentiation.", "mechanism": "CLEC5A upregulation after mRNA vaccination marks enhanced innate and adaptive immune activation.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "biomarker", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans modulate immune recognition and receptor binding.", "mechanism": "Spike protein mediates viral entry and immune activation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Spike glycan recognition triggers CLEC5A signaling.", "mechanism": "Exacerbated CLEC5A expression on inflammatory monocytes drives cytokine production and poor outcomes.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "causal", "source_pmcid": "PMC12474447" }, { "confidence": "medium", "disease": "Yellow fever", "glycan_involvement": "CLEC5A recognizes viral glycoproteins.", "mechanism": "CLEC5A activation bridges innate and adaptive immunity post-vaccination.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "protective", "source_pmcid": "PMC12474447" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binds high-mannose glycans on spike.", "mechanism": "Forms heterocomplexes with CLEC5A to enhance viral glycan recognition and immune activation.", "protein": "DC-SIGN", "relationship_type": "co-receptor/biomarker", "source_pmcid": "PMC12474447" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TLR2 may interact with glycosylated viral proteins.", "mechanism": "TLR2 upregulation with CLEC5A drives inflammation in SARS-CoV-2 infection.", "protein": "TLR2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12474447" }, { "confidence": "medium", "disease": "Adaptive immune activation", "glycan_involvement": "CD86 is a glycoprotein; glycosylation affects surface expression.", "mechanism": "CD86 upregulation on monocytes/APCs after mRNA vaccination signals T cell activation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "Vaccine-induced immunity", "glycan_involvement": "Glycosylation modulates immunogenicity and epitope presentation.", "mechanism": "Spike glycoprotein expression induces robust antibody and memory T/B cell responses.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "protective", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Recognition of spike glycans initiates signaling.", "mechanism": "CLEC5A activation triggers inflammatory cytokine release (IL-1\u03b2, TNF) in response to spike glycoprotein.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "causal", "source_pmcid": "PMC12474447" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation affects aggregation and clearance; AGE modification stabilizes A\u03b2 fibrils.", "mechanism": "A\u03b2 accumulation forms plaques, drives neurodegeneration and cognitive decline.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "O-glycosylation and AGE modification promote tau aggregation and phosphorylation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, leading to synaptic dysfunction.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation required for IR function; altered glycosylation impairs signaling.", "mechanism": "Reduced IR density and signaling in brain impairs glucose metabolism, promotes A\u03b2 and tau pathology.", "protein": "Insulin receptor (IR)", "relationship_type": "causal", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation modulates IDE stability and activity.", "mechanism": "IDE degrades insulin and A\u03b2; reduced activity increases A\u03b2 accumulation.", "protein": "Insulin-degrading enzyme (IDE)", "protein_enriched": { "function": "Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular pept", "gene_name": "IDE", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14735" }, "relationship_type": "causal", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation of RAGE affects ligand binding and signaling.", "mechanism": "AGE-RAGE signaling amplifies neuroinflammation, stabilizes A\u03b2, promotes tau phosphorylation.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12474712" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "GLP-1 agonists improve insulin sensitivity, reduce A\u03b2/tau pathology.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation modulates BACE1 activity and trafficking.", "mechanism": "BACE1 cleaves APP, increases A\u03b2 production; upregulated in T2D and AD.", "protein": "BACE1 (Beta-secretase 1)", "protein_enriched": { "function": "Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generatio", "gene_name": "BACE1", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G80920RR", "G05724UK", "G06110VR", "G12398HZ", "G14023ZV", "G14669DU", "G15065YV", "G17689DH", "G21112KH", "G22310AV", "G22768VO", "G23863VK", "G25520XG", "G29880MM", "G39188ZX", "G44444MB", "G46687AB", "G49874UX", "G55220VL", "G60230HH", "G63889NK", "G64527OM", "G70101JE", "G70375MX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G80966KZ", "G84452RH", "G87618BG", "G90093AU", "G91636VS", "G93993PD", "G94854LT" ], "uniprot_id": "P56817" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12474712" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation may regulate kinase activity.", "mechanism": "GSK-3\u03b2 hyperactivity drives tau phosphorylation and neurodegeneration.", "protein": "Glycogen Synthase Kinase-3 beta (GSK-3\u03b2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12474712" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "N-glycosylation essential for LRP1 function and trafficking.", "mechanism": "LRP1 mediates A\u03b2 clearance across BBB; reduced expression in T2D/AD impairs clearance.", "protein": "Low-density lipoprotein receptor-related protein 1 (LRP1)", "relationship_type": "protective", "source_pmcid": "PMC12474712" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Potential O-glycosylation affects stability and activity.", "mechanism": "PGC-1\u03b1 promotes mitochondrial biogenesis; reduced expression linked to cognitive decline.", "protein": "PGC-1\u03b1 (PPARGC1A)", "relationship_type": "protective", "source_pmcid": "PMC12474712" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors the DGC, which contains glycoproteins essential for sarcolemmal stability.", "mechanism": "Loss of dystrophin leads to destabilization of the DGC, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "DGC contains glycosylated proteins (e.g., dystroglycans) critical for muscle membrane stability.", "mechanism": "Loss of DGC due to dystrophin deficiency disrupts sarcolemmal integrity and muscle function.", "protein": "Dystrophin-associated glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin is a heavily glycosylated ECM protein interacting with DGC.", "mechanism": "Laminin staining used to assess muscle fiber size and regeneration in DMD models.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12475182" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Ltbp4 is a glycoprotein modulating TGF-\u03b2 bioavailability.", "mechanism": "Ltbp4 variants enhance TGF-\u03b21 activation, promoting fibrosis in DMD models.", "protein": "Latent TGF-\u03b2 binding protein 4 (Ltbp4)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK3", "glycan_count": 16, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22310AV", "G41247ZX", "G45395BF", "G57888GL", "G62765YT", "G80920RR", "G00273SJ", "G06356OH", "G07246CJ", "G48414YA", "G49955PK", "G92275SC", "G29931IJ", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "Q9UBP4" }, "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential glycosylation may affect membrane association.", "mechanism": "Anxa6 variants impair membrane repair and muscle regeneration, worsening DMD pathology.", "protein": "Annexin A6 (Anxa6)", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "Anxa6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14824" }, "relationship_type": "modifier", "source_pmcid": "PMC12475182" }, { "confidence": "medium", "disease": "Muscle calcification", "glycan_involvement": "Indirect; ABCC6 may interact with glycoprotein complexes.", "mechanism": "ABCC6 locus variants associated with muscle and heart calcifications in D2-mdx mice.", "protein": "ABCC6", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugate", "gene_name": "ABCC6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95255" }, "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "medium", "disease": "Muscle calcification", "glycan_involvement": "EMP3 is a membrane protein, possibly glycosylated.", "mechanism": "EMP3 locus variants linked to muscle calcification in D2-mdx mice.", "protein": "EMP3", "protein_enriched": { "function": "Probably involved in cell proliferation and cell-cell interactions", "gene_name": "EMP3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT", "G81637OR" ], "uniprot_id": "P54852" }, "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation of DGC components is essential for function.", "mechanism": "Loss of DGC increases susceptibility to fibrosis due to membrane instability.", "protein": "Dystrophin-associated glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12475182" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation affects laminin's ECM interactions.", "mechanism": "Laminin immunostaining quantifies muscle fiber size and fibrosis.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12475182" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Proper glycosylation of DGC components is required for therapeutic efficacy.", "mechanism": "Restoration of DGC function is a therapeutic goal in DMD.", "protein": "Dystrophin-associated glycoprotein complex (DGC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12475182" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation of MOG influences antigenicity and antibody binding.", "mechanism": "Anti-MOG antibodies in serum are diagnostic for MOGAD and correlate with disease activity and relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12476541" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation modulates immune recognition of MOG.", "mechanism": "Autoantibodies against MOG trigger CNS demyelination via immune-mediated attack.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12476541" }, { "confidence": "medium", "disease": "Beh\u00e7et's disease", "glycan_involvement": "Not directly addressed; possible modulation of immune response via glycoprotein interactions.", "mechanism": "Background immune dysregulation in Beh\u00e7et's disease may predispose to MOGAD and increase relapse risk.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "risk modifier", "source_pmcid": "PMC12476541" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation affects AQP4 antigenicity.", "mechanism": "Anti-AQP4 antibodies are diagnostic for NMOSD, distinguishing it from MOGAD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12476541" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation status may affect antibody specificity.", "mechanism": "Anti-MOG antibodies are negative in NMOSD, helping to differentiate from MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12476541" }, { "confidence": "medium", "disease": "Longitudinally extensive transverse myelitis (LETM)", "glycan_involvement": "Glycosylation may influence MOG antigen presentation in CNS.", "mechanism": "Anti-MOG antibodies are associated with LETM presentation in MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12476541" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Not directly addressed.", "mechanism": "Immunosuppressive therapies (e.g., Mycophenolate Mofetil) reduce relapse by targeting immune response to MOG.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12476541" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may affect antibody persistence and immune recognition.", "mechanism": "Persistence of anti-MOG antibodies correlates with increased risk of relapse.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "relapse risk marker", "source_pmcid": "PMC12476541" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation status may affect assay sensitivity.", "mechanism": "Live cell-based assay for anti-MOG antibodies confirms diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "diagnostic marker", "source_pmcid": "PMC12476541" }, { "confidence": "low", "disease": "Beh\u00e7et's disease", "glycan_involvement": "Not directly addressed.", "mechanism": "Rare co-occurrence; Beh\u00e7et's disease may act as a predisposing factor for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "comorbidity", "source_pmcid": "PMC12476541" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Altered N-glycosylation of M2BP detected by Wisteria floribunda agglutinin.", "mechanism": "Serum M2BPGi levels reflect degree of liver fibrosis and cirrhosis severity.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Disease-associated N-glycan changes on M2BP increase lectin binding.", "mechanism": "Elevated M2BPGi predicts risk and presence of HCC in cirrhotic patients.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "medium", "disease": "Esophageal varices (EV)", "glycan_involvement": "Fibrosis-driven glycosylation changes in M2BP reflect portal hypertension.", "mechanism": "Higher M2BPGi levels correlate with presence and severity of EV.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "high", "disease": "Liver decompensation", "glycan_involvement": "N-glycosylation changes indicate advanced fibrogenesis.", "mechanism": "M2BPGi is an independent risk factor for liver decompensation in cirrhosis.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation isomer status enhances diagnostic specificity.", "mechanism": "Combining M2BPGi with AFP improves sensitivity and accuracy for HCC detection.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "N-glycan changes reflect severity of portal hypertension.", "mechanism": "M2BPGi levels correlate with hepatic venous pressure gradient.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "medium", "disease": "High-risk esophageal varices", "glycan_involvement": "Disease-specific glycosylation changes increase lectin binding.", "mechanism": "Elevated M2BPGi predicts high-risk EV in cirrhosis.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "high", "disease": "Fibrosis (liver)", "glycan_involvement": "Altered N-glycosylation is a marker of HSC activation.", "mechanism": "M2BPGi reflects activation of hepatic stellate cells and fibrogenesis.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "N-glycan changes reflect disease progression.", "mechanism": "M2BPGi correlates with fibrosis stage in autoimmune hepatitis.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease", "glycan_involvement": "Fibrosis-associated N-glycosylation changes.", "mechanism": "M2BPGi levels indicate fibrosis stage in metabolic liver disease.", "protein": "M2BPGi", "relationship_type": "biomarker", "source_pmcid": "PMC12476715" }, { "confidence": "high", "disease": "Epstein-Barr virus infection", "glycan_involvement": "N-linked glycans on gp350 facilitate host cell binding and immune modulation.", "mechanism": "EBV glycoproteins mediate viral entry and immune evasion, leading to infection.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350)", "relationship_type": "causal", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation of EBV envelope proteins influences host immune response.", "mechanism": "EBV infection triggers immune-mediated muscle damage, leading to rhabdomyolysis.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350)", "relationship_type": "causal", "source_pmcid": "PMC12477421" }, { "confidence": "high", "disease": "Epstein-Barr virus infection", "glycan_involvement": "N-glycosylation affects IgM stability and immune recognition.", "mechanism": "Elevated EBV-specific IgM indicates acute EBV infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "high", "disease": "Epstein-Barr virus infection", "glycan_involvement": "Fc glycosylation modulates IgG effector functions.", "mechanism": "EBV-specific IgG indicates past or ongoing infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may affect renal clearance and toxicity.", "mechanism": "Elevated myoglobin in urine is a marker of muscle breakdown.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation can influence enzyme stability.", "mechanism": "High CK-MB levels reflect muscle injury.", "protein": "Creatine kinase-MB (CK-MB)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with larg", "gene_name": "CKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated LDH indicates tissue damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation can modulate enzyme function.", "mechanism": "High AST is a marker of muscle and liver injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may impact enzyme stability.", "mechanism": "Elevated ALT reflects muscle and liver damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12477421" }, { "confidence": "medium", "disease": "Acute compartment syndrome", "glycan_involvement": "Viral glycoprotein glycosylation modulates host immune response and tissue damage.", "mechanism": "EBV-induced rhabdomyolysis leads to muscle swelling and compartment syndrome.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350)", "relationship_type": "causal (indirect)", "source_pmcid": "PMC12477421" }, { "confidence": "high", "disease": "Spinal Bulbar Muscular Atrophy (SBMA)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Expanded CAG repeats in AR gene cause toxic gain-of-function leading to neuromuscular degeneration.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Brugada Syndrome", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Mutant AR accumulates in cardiac nuclei, associated with decreased SCN5A expression and cardiac arrhythmias.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Brugada Syndrome", "glycan_involvement": "SCN5A is a glycoprotein, but specific glycan involvement not described in this context.", "mechanism": "Reduced expression of SCN5A in myocardium contributes to arrhythmogenic risk.", "protein": "SCN5A", "relationship_type": "causal", "source_pmcid": "PMC12479135" }, { "confidence": "low", "disease": "Cardiomyopathy", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Nuclear accumulation of mutant AR in cardiac muscle may contribute to cardiac dysfunction.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal (possible)", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Androgen insensitivity due to mutant AR leads to metabolic dysfunction and NAFLD.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Androgen insensitivity contributes to insulin resistance and diabetes.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Osteopenia/Reduced Bone Mineral Density", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Androgen insensitivity leads to reduced bone mineral density.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Gynecomastia", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Androgen insensitivity results in hormonal imbalance and gynecomastia.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12479135" }, { "confidence": "medium", "disease": "Testicular Atrophy/Reduced Fertility", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Androgen insensitivity impairs reproductive function.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12479135" }, { "confidence": "low", "disease": "Cardiomyopathy", "glycan_involvement": "SCN5A is a glycoprotein, but no specific glycan modification described.", "mechanism": "Decreased SCN5A expression in myocardium may contribute to cardiac dysfunction in SBMA.", "protein": "SCN5A", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12479135" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Binds \u03b2-galactoside glycans; glycosylation affects lectin activity.", "mechanism": "Regulates PANoptosis via ROS pathway, modulating fibrotic response.", "protein": "Galectin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "O-GlcNAc glycosylation modulates activity and substrate selectivity.", "mechanism": "Central integrator of apoptosis, necroptosis, and pyroptosis in PANoptosis; regulates renal inflammation.", "protein": "Caspase-8", "protein_enriched": { "function": "Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic devel", "gene_name": "CASP8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14790" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "AKI", "glycan_involvement": "N-glycosylation may affect inflammasome assembly (not directly shown).", "mechanism": "Inflammasome activation drives PANoptosis and renal tubular injury; inhibition reduces inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "Potential glycosylation modulates protein stability (not directly shown).", "mechanism": "AIM2-PANoptosome formation triggers PANoptosis in sepsis and IRI models.", "protein": "AIM2", "protein_enriched": { "function": "Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:17", "gene_name": "AIM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14862" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "medium", "disease": "Renal Tumors (ccRCC)", "glycan_involvement": "Glycosylation may affect sensor function (not directly shown).", "mechanism": "ZBP1-dependent PANoptosis removes malignant cells; high expression linked to poor prognosis.", "protein": "ZBP1", "protein_enriched": { "function": "Acts as an E3 ubiquitin-protein ligase able to ubiquitinate p53/TP53 which promotes its relocalization to discrete foci associated with PML nuclear bodies. Exhibits preference for UBE2D2 as a E2 enzym", "gene_name": "RNF38", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0F5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "DKD", "glycan_involvement": "N-glycosylation required for receptor binding and signaling.", "mechanism": "TRAIL/DR5 axis activates PANoptosis in podocytes, leading to glomerulosclerosis.", "protein": "TRAIL (TNFSF10)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (PubMed:10549288, PubMed:26457518). Induces apoptosis. Its activity", "gene_name": "TNFSF10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P50591" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "DKD", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "DR5 mediates PANoptosis in podocytes upon TRAIL binding; correlates with DKD severity.", "protein": "DR5 (TNFRSF10B)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "AKI", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Released during PANoptosis, amplifies renal inflammation and injury.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12481750" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "Glycosylation regulates extracellular release.", "mechanism": "DAMP released during PANoptosis, drives inflammation and tissue damage.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12481750" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "Potential O-glycosylation may affect membrane targeting (not directly shown).", "mechanism": "Executor of pyroptosis in PANoptosis; pore formation leads to cell lysis and inflammation.", "protein": "GSDMD", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12481750" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function", "mechanism": "Marker of systemic inflammation, associated with increased CVD risk", "protein": "High-sensitivity C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "LDL glycosylation affects receptor binding and atherogenicity", "mechanism": "LDL contributes to atherosclerosis; glycosylation modulates clearance and aggregation", "protein": "Low-density lipoprotein", "relationship_type": "causal", "source_pmcid": "PMC12481991" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties", "mechanism": "HDL is anti-atherogenic; glycosylation influences cholesterol efflux", "protein": "High-density lipoprotein", "relationship_type": "protective", "source_pmcid": "PMC12481991" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation affects CRP's inflammatory activity", "mechanism": "Elevated CRP predicts stroke risk via inflammation", "protein": "High-sensitivity C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Hyperglycemia increases protein glycation/glycosylation, affecting vascular proteins", "mechanism": "TyG index reflects insulin resistance, predicts CVD risk", "protein": "Triglyceride-glucose index (TyG, composite)", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "high", "disease": "Ischemic heart disease", "glycan_involvement": "Glycation/glycosylation of vascular proteins promotes atherosclerosis", "mechanism": "Higher TyG index strongly predicts ischemic heart disease in prediabetes", "protein": "Triglyceride-glucose index (TyG, composite)", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Hyperglycemia-induced glycosylation affects vascular integrity", "mechanism": "TyG index predicts stroke risk, especially ischemic stroke", "protein": "Triglyceride-glucose index (TyG, composite)", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Non-enzymatic glycation of hemoglobin and vascular proteins", "mechanism": "Elevated glucose leads to protein glycation, increasing CVD risk", "protein": "Fasting blood glucose (as glycosylated hemoglobin proxy)", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation modulates CRP's pro-inflammatory effects", "mechanism": "CRP elevation indicates inflammation, associated with ischemic events", "protein": "High-sensitivity C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "low", "disease": "Hemorrhagic stroke", "glycan_involvement": "Not applicable", "mechanism": "No significant association found", "protein": "Triglyceride-glucose index (TyG, composite)", "relationship_type": "biomarker", "source_pmcid": "PMC12481991" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG trigger immune-mediated CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12482636" }, { "confidence": "medium", "disease": "MS", "glycan_involvement": "Glycosylation of MOG may influence immune recognition and disease phenotype.", "mechanism": "Anti-MOG antibodies can mimic MS-like clinical and radiological features, complicating diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation status may affect antibody binding and detection.", "mechanism": "Anti-MOG antibody titers in serum/CSF are diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects their function and detection.", "mechanism": "OCB positivity in CSF is associated with increased risk of relapse and MS-like progression in MOGAD.", "protein": "Oligoclonal bands (OCB, immunoglobulins)", "relationship_type": "biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "MS", "glycan_involvement": "Immunoglobulin glycosylation influences immune response and biomarker reliability.", "mechanism": "OCB positivity is a classic biomarker for MS diagnosis.", "protein": "Oligoclonal bands (OCB, immunoglobulins)", "relationship_type": "biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "medium", "disease": "Autoimmune encephalitis (NMDAR-Ab positive)", "glycan_involvement": "NMDAR is a glycoprotein; glycosylation may affect antibody binding and pathogenicity.", "mechanism": "Autoantibodies against NMDAR cause autoimmune encephalitis.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12482636" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "Glycosylation may affect antigenic specificity.", "mechanism": "Anti-MOG antibodies help distinguish MOGAD from NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation of immunoglobulins may affect their persistence and detection in CSF.", "mechanism": "OCB positivity predicts higher risk of relapse and radiological progression in MOGAD.", "protein": "Oligoclonal bands (OCB, immunoglobulins)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12482636" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may influence MOG's immunogenicity and response to therapy.", "mechanism": "Immunosuppressive therapies (e.g., corticosteroids, MMF) target the autoimmune response against MOG.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation affects immunoglobulin detection and disease association.", "mechanism": "OCB positivity complicates differentiation between MOGAD and MS.", "protein": "Oligoclonal bands (OCB, immunoglobulins)", "relationship_type": "diagnostic challenge", "source_pmcid": "PMC12482636" }, { "confidence": "high", "disease": "HEV infection", "glycan_involvement": "IgM is heavily glycosylated, affecting stability and immune recognition.", "mechanism": "Serological marker for acute HEV infection in transplant recipients.", "protein": "HEV IgM", "relationship_type": "biomarker", "source_pmcid": "PMC12483739" }, { "confidence": "high", "disease": "HEV infection", "glycan_involvement": "IgG glycosylation modulates effector function and half-life.", "mechanism": "Indicates prior exposure to HEV; used for epidemiological assessment.", "protein": "HEV IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12483739" }, { "confidence": "high", "disease": "HEV infection", "glycan_involvement": "N-glycosylation of ORF2 modulates infectivity and immune escape.", "mechanism": "Major structural protein of HEV; mediates viral entry and immune evasion.", "protein": "HEV ORF2 capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12483739" }, { "confidence": "medium", "disease": "CMV infection", "glycan_involvement": "N- and O-glycosylation critical for viral infectivity and immune evasion.", "mechanism": "CMV glycoproteins mediate cell entry and immune modulation.", "protein": "CMV glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12483739" }, { "confidence": "medium", "disease": "EBV infection", "glycan_involvement": "Glycosylation affects tropism and immune recognition.", "mechanism": "EBV glycoproteins facilitate host cell entry and immune modulation.", "protein": "EBV glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12483739" }, { "confidence": "high", "disease": "HBV infection", "glycan_involvement": "N-glycosylation influences antigenicity and immune escape.", "mechanism": "HBsAg is used for diagnosis of HBV infection.", "protein": "HBV surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12483739" }, { "confidence": "high", "disease": "HCV infection", "glycan_involvement": "Extensive N-glycosylation shields epitopes from neutralizing antibodies.", "mechanism": "E1/E2 mediate viral entry and immune evasion.", "protein": "HCV envelope glycoproteins (E1/E2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12483739" }, { "confidence": "medium", "disease": "Acute rejection", "glycan_involvement": "Glycosylation may affect protein stability and drug binding.", "mechanism": "FKBP12 binds tacrolimus, inhibiting T-cell activation and preventing rejection.", "protein": "Tacrolimus-binding protein FKBP12", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12483739" }, { "confidence": "medium", "disease": "Allograft hepatitis", "glycan_involvement": "Fc glycosylation modulates inflammatory activity.", "mechanism": "IgG levels may indicate immune response to viral or rejection injury.", "protein": "Human immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC12483739" }, { "confidence": "medium", "disease": "Acute rejection", "glycan_involvement": "Glycosylation affects complement activation and clearance.", "mechanism": "IgM elevation may reflect acute immune activation.", "protein": "Human immunoglobulin M", "relationship_type": "biomarker", "source_pmcid": "PMC12483739" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation increases MUC1 stability and function.", "mechanism": "Overexpression promotes proliferation, invasion, and poor prognosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12484618" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation critical for MUC4 function.", "mechanism": "Overexpression associated with increased proliferation and invasion.", "protein": "MUC4", "protein_enriched": { "function": "Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces (PubMed:10880978). These g", "gene_name": "MUC4", "glycan_count": 17, "glycosylation_sites_count": 547, "glytoucan_ids": [ "G57321FI", "G00031MO", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G42665KV", "G47325XO", "G49108TO", "G49582PC", "G58272ZE", "G60145BJ", "G63628AV", "G64973KT", "G74722FL", "G76163CP", "G94435QH" ], "uniprot_id": "Q99102" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12484618" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Modified by complex, fucosylated, and sialylated glycans.", "mechanism": "Highly enriched in glioma cells; depletion inhibits proliferation.", "protein": "U2 snRNA (glycoRNA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12484618" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Modified by complex, fucosylated, and sialylated glycans.", "mechanism": "Highly enriched in glioma cells; depletion inhibits proliferation.", "protein": "U4 snRNA (glycoRNA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Glycosylated; specific glycan types not detailed.", "mechanism": "Enriched in glioma and other cell types; potential marker.", "protein": "Y5 RNA (glycoRNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "N-glycosylation affects folding and trafficking.", "mechanism": "N-glycosylation at Asn50 essential for proliferation and metastasis.", "protein": "SND1", "protein_enriched": { "function": "Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase", "gene_name": "SND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7KZF4" }, "relationship_type": "causal", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Glycosylation required for PTPRZ stability.", "mechanism": "Reduced by deficiency of glycosylation enzyme GnT-IX, inhibiting growth.", "protein": "PTPRZ", "relationship_type": "causal", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "N-glycan maturation affects immune recognition.", "mechanism": "Altered glycosylation by MAN1A1 inhibition activates T-cell immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Sialic acid addition to glycoprotein.", "mechanism": "Sialylation mediates signaling, promoting growth and invasion.", "protein": "\u03b21 integrin", "relationship_type": "causal", "source_pmcid": "PMC12484618" }, { "confidence": "medium", "disease": "Immune evasion", "glycan_involvement": "Recognition of sialylated glycans on glycoRNAs/glycoproteins.", "mechanism": "Bind sialylated glycoRNAs/glycoproteins, mediating immune suppression.", "protein": "Siglec receptors", "relationship_type": "causal", "source_pmcid": "PMC12484618" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycosylated DGC proteins to the cytoskeleton; loss impairs glycoprotein complex function.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex, destabilizing muscle fibers and causing degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12485293" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Partial restoration of DGC glycoprotein interactions; glycosylation status preserved.", "mechanism": "Internally truncated dystrophin (from exon 51\u201352 deletion) partially restores DGC, resulting in milder muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12485293" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Highly glycosylated; glycosylation critical for ECM binding; loss of dystrophin disrupts complex.", "mechanism": "Reduced abundance due to loss of dystrophin; impairs linkage between ECM and cytoskeleton.", "protein": "Dystroglycan (\u03b1/\u03b2)", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "Dag1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43769HG", "G64527OM", "G49108TO", "G95177YH", "G57292HF", "G87015RU", "G80510PV" ], "uniprot_id": "Q62165" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12485293" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Sarcoglycans are glycoproteins; glycosylation required for membrane localization and function.", "mechanism": "Reduced abundance in DMD muscle; destabilization of DGC leads to muscle pathology.", "protein": "Sarcoglycans", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12485293" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin is a glycoprotein; glycosylation mediates DGC binding.", "mechanism": "Disrupted interaction with DGC impairs muscle fiber stability.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12485293" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Collagen is glycosylated; glycosylation affects ECM structure.", "mechanism": "Increased collagen deposition marks fibrosis in DMD muscle.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12485293" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Myosin heavy chains can be glycosylated; changes may affect muscle contractility.", "mechanism": "Altered expression (reduced MYH7, MYH1, MYH2) reflects fiber type switching and muscle pathology.", "protein": "Myosin Heavy Chain Isoforms", "relationship_type": "biomarker", "source_pmcid": "PMC12485293" }, { "confidence": "high", "disease": "Muscle weakness", "glycan_involvement": "DGC integrity depends on glycosylated components for membrane stability.", "mechanism": "Loss or reduction of DGC proteins leads to decreased muscle force and endurance.", "protein": "Dystrophin-glycoprotein complex (DGC)", "relationship_type": "causal", "source_pmcid": "PMC12485293" }, { "confidence": "medium", "disease": "Cardiac dysfunction", "glycan_involvement": "DGC disruption affects glycoprotein-mediated cardiac muscle stability.", "mechanism": "Absence of dystrophin leads to cardiac muscle degeneration and dysfunction.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12485293" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Proper glycosylation and DGC assembly preserved in BMD.", "mechanism": "Near-normal abundance in BMD muscle supports improved muscle integrity.", "protein": "Dystroglycan (\u03b1/\u03b2)", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "Dag1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43769HG", "G64527OM", "G49108TO", "G95177YH", "G57292HF", "G87015RU", "G80510PV" ], "uniprot_id": "Q62165" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12485293" }, { "confidence": "high", "disease": "Advanced gastric cancer", "glycan_involvement": "Aberrant paucimannosylation of MMP9 correlates with aggressiveness.", "mechanism": "MMP9 expression increases with tumor stage and grade; co-expression with paucimannosidic N-glycans predicts worst prognosis.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Trimmed N-glycans (paucimannose) on MMP9.", "mechanism": "Cancer-specific expression and glycosylation make MMP9 a potential target.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486017" }, { "confidence": "medium", "disease": "Advanced gastric cancer", "glycan_involvement": "Paucimannosylation detected by glycoproteomics.", "mechanism": "Identified as a carrier of trimmed N-glycans in advanced-stage tumors.", "protein": "CEACAM6", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion and tumor progression (PubMed:10910050, PubMed:11590190, PubMed:1378450, PubMed:16204051, PubMed:2022629, PubMed:2803308, PubMed:8776764). ", "gene_name": "CEACAM6", "glycan_count": 10, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G53434XO", "G71784JC", "G92050GC", "G62765YT", "G28681TP", "G80920RR", "G57321FI" ], "uniprot_id": "P40199" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "medium", "disease": "Advanced gastric cancer", "glycan_involvement": "Confirmed paucimannose N-glycan modification.", "mechanism": "Ribosomal protein with paucimannosylation, associated with advanced stage.", "protein": "RPS11", "protein_enriched": { "function": "Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first pre", "gene_name": "RPS11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62280" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "high", "disease": "Advanced gastric cancer", "glycan_involvement": "Altered glycosylation may affect cell adhesion.", "mechanism": "Loss of E-cadherin correlates with progression and poor prognosis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "high", "disease": "Metastatic gastric cancer", "glycan_involvement": "Sialylated Lewis antigen (N-/O-glycan epitope).", "mechanism": "sLeA associated with distant metastasis and reduced survival.", "protein": "sLeA antigen (CA19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Premature truncation of O-glycosylation.", "mechanism": "sTn linked to reduced survival.", "protein": "sTn antigen (TAG-72)", "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "medium", "disease": "Advanced gastric cancer", "glycan_involvement": "Potential N-glycosylation changes.", "mechanism": "Elevated in advanced-stage tumors; immune modulation.", "protein": "HLA-DRB1", "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "medium", "disease": "Early-stage gastric cancer", "glycan_involvement": "N-glycosylation involved in ECM interactions.", "mechanism": "Underexpressed as disease progresses; may suppress tumor growth.", "protein": "DCN (Decorin)", "protein_enriched": { "function": "May affect the rate of fibrils formation", "gene_name": "DCN", "glycan_count": 197, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08918WF", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G12313PD", "G13131HA", "G13191RB", "G14994KB", "G17208MA", "G18647XP", "G20425TQ", "G23294PN", "G23432EQ", "G23453IV", "G23719VF", "G23863VK", "G24084IV", "G24528MX", "G24835MQ", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G31852PQ", "G31916IQ", "G31986NC", "G33609NS", "G35253PZ", "G37399XV", "G37412TK", "G37509XX", "G37818NZ", "G39188ZX", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G44215PV", "G45395BF", "G45504EY", "G46687AB", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G48414YA", "G49018RC", "G49955PK", "G50045TK", "G52527GH", "G54010QB", "G55132BD", "G55383ZG", "G56307ZW", "G57317CE", "G57776ZU", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G65184UU", "G70223PD", "G70418MS", "G70619PT", "G70888PK", "G72291OX", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G73968GN", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80333GO", "G80920RR", "G81295CK", "G82119TF", "G82463GQ", "G82830MN", "G83633GK", "G83646BJ", "G84452RH", "G84820NF", "G85269DF", "G85554PZ", "G86182NS", "G86880BF", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G95865ZB", "G95977AE", "G99668VU", "G02030ZB", "G03382KH", "G03644CB", "G07246CJ", "G07755XJ", "G07810QS", "G08290VR", "G11629QQ", "G11870QZ", "G14972EH", "G15169WU", "G20210JR", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G24954UD", "G26403SG", "G27915IV", "G34617SM", "G34989PA", "G35541EV", "G36379GD", "G37995HC", "G43223CG", "G46503DX", "G46524LG", "G47950XN", "G49874UX", "G50757KG", "G51640FO", "G57776ZS", "G63041LO", "G63381RX", "G63980BQ", "G64409MC", "G65092SV", "G66760KM", "G70232NH", "G70441OD", "G70822IO", "G72667IM", "G72797UR", "G75418YA", "G80075MS", "G80223IX", "G81198YO", "G81263BG", "G84862VB", "G86795LJ", "G87123QX", "G87389XI", "G87661QW", "G90093AU", "G90382BL", "G90734RJ", "G91636VS", "G92135MA", "G93718GY", "G96091TT", "G12341GU", "G28622IK", "G43669FQ", "G64394MX", "G65000LJ", "G49108TO" ], "uniprot_id": "P07585" }, "relationship_type": "protective", "source_pmcid": "PMC12486017" }, { "confidence": "medium", "disease": "Advanced gastric cancer", "glycan_involvement": "Potential N-glycosylation.", "mechanism": "Overexpressed in advanced-stage tumors; involved in immune modulation.", "protein": "IFI30", "relationship_type": "biomarker", "source_pmcid": "PMC12486017" }, { "confidence": "high", "disease": "Cancer (general, including lymphoma)", "glycan_involvement": "Glycan modification of nanoparticles (\u03b1-mannose or sialic acid) modulates uptake and immune activation.", "mechanism": "OVA peptide presented by MHC I on APCs induces antigen-specific CD8+ T cell responses, leading to anti-tumor immunity.", "protein": "Ovalbumin (OVA) peptide (SIINFEKL/SGLEQLESIINFEKL)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "Cancer (general, including lymphoma)", "glycan_involvement": "CD86 expression is increased upon uptake of glycan-modified nanovaccines.", "mechanism": "Upregulation of CD86 on dendritic cells indicates maturation and enhanced antigen presentation, correlating with effective anti-tumor immune response.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486328" }, { "confidence": "medium", "disease": "Cancer (general, including lymphoma)", "glycan_involvement": "Triggered by uptake of \u03b1-mannose-modified GNPs; less so with sialic acid unless peptide is present.", "mechanism": "Nuclear translocation of NF-\u03baB p65 in BMDCs signals activation of inflammatory pathways essential for anti-tumor immunity.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "Cancer (general, including lymphoma)", "glycan_involvement": "Glycan modification affects delivery and activation efficiency.", "mechanism": "Activation of TLR7 by ligand (1V209) on GNPs stimulates type I interferon and inflammatory responses, enhancing anti-tumor immunity.", "protein": "TLR7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "Cancer (general, including lymphoma)", "glycan_involvement": "Direct recognition of \u03b1-mannose glycan on nanoparticles.", "mechanism": "Facilitates uptake of \u03b1-mannose-modified nanoparticles by dendritic cells, promoting antigen presentation and immune activation.", "protein": "Mannose receptor (CD206)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "EG7 T lymphoma", "glycan_involvement": "Glycan modification of vaccine nanoparticles modulates delivery but is overridden by peptide presence.", "mechanism": "OVA-expressing EG7 cells are targeted by OVA-specific CD8+ T cells induced by glyco-nanovaccine.", "protein": "Ovalbumin (OVA) peptide (SIINFEKL/SGLEQLESIINFEKL)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "EG7 T lymphoma", "glycan_involvement": "Glycan type influences uptake and activation, but peptide presence equalizes effect.", "mechanism": "TLR7 ligand on nanoparticles activates dendritic cells, enhancing anti-EG7 immune response.", "protein": "TLR7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "EG7 T lymphoma", "glycan_involvement": "Both \u03b1-mannose and sialic acid glycan-modified vaccines induce CD86 when peptide is present.", "mechanism": "CD86 upregulation on APCs correlates with effective induction of anti-EG7 cytotoxic T cells.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "EG7 T lymphoma", "glycan_involvement": "Direct interaction with \u03b1-mannose glycan.", "mechanism": "Mediates uptake of \u03b1-mannose-modified nanovaccines, enhancing antigen delivery to APCs.", "protein": "Mannose receptor (CD206)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486328" }, { "confidence": "medium", "disease": "EG7 T lymphoma", "glycan_involvement": "Activation depends on glycan type unless peptide is present.", "mechanism": "NF-\u03baB activation in APCs is a marker of immune stimulation by nanovaccine.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486328" }, { "confidence": "high", "disease": "Oligodendroglioma, IDH-mutant, 1p/19q-codeleted, grade 2", "glycan_involvement": "P-gp is a glycoprotein; glycosylation is required for proper folding and membrane localization.", "mechanism": "High endothelial P-gp expression indicates preserved BBB integrity and low-grade tumor phenotype.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Glioblastoma, IDH-wildtype", "glycan_involvement": "Glycosylation affects P-gp stability and drug efflux function.", "mechanism": "Reduced endothelial P-gp expression marks BBB disruption; increased P-gp in tumor cells and vessel walls correlates with multidrug resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Glioblastoma, IDH-wildtype", "glycan_involvement": "CD146 is a glycoprotein; glycosylation modulates cell adhesion and signaling.", "mechanism": "High CD146 in endothelial and tumor cells marks vascular dedifferentiation, stemness, and aggressive phenotype.", "protein": "CD146 (MCAM/MUC18)", "protein_enriched": { "function": "Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873)", "gene_name": "ANAPC4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UJX5" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Astrocytoma, IDH-mutant, grade 4", "glycan_involvement": "Glycosylation influences CD146-mediated cell interactions.", "mechanism": "Elevated CD146 in proliferating vessels and tumor cells correlates with high-grade, mesenchymal-like phenotype.", "protein": "CD146 (MCAM/MUC18)", "protein_enriched": { "function": "Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873)", "gene_name": "ANAPC4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UJX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Astrocytoma, IDH-mutant, grade 4", "glycan_involvement": "Glycosylation required for P-gp function.", "mechanism": "Decreased endothelial P-gp expression reflects BBB breakdown and higher tumor grade.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Oligodendroglioma, IDH-mutant, 1p/19q-codeleted, grade 2", "glycan_involvement": "CD146 glycosylation maintains normal endothelial phenotype.", "mechanism": "Low CD146 expression in endothelium and tumor cells indicates mature BBB and low malignancy.", "protein": "CD146 (MCAM/MUC18)", "protein_enriched": { "function": "Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873)", "gene_name": "ANAPC4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UJX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "medium", "disease": "Oligodendroglioma, IDH-mutant, 1p/19q-codeleted, grade 3", "glycan_involvement": "Glycosylation impacts P-gp localization.", "mechanism": "Intermediate endothelial P-gp expression; loss in proliferating vessels signals partial BBB disruption.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "medium", "disease": "Oligodendroglioma, IDH-mutant, 1p/19q-codeleted, grade 3", "glycan_involvement": "Glycosylation modulates CD146 function.", "mechanism": "Increased CD146 in tumor and endothelial cells correlates with anaplastic features and vascular remodeling.", "protein": "CD146 (MCAM/MUC18)", "protein_enriched": { "function": "Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873)", "gene_name": "ANAPC4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UJX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "medium", "disease": "Astrocytoma, IDH-mutant, grade 3", "glycan_involvement": "Glycosylation required for P-gp activity.", "mechanism": "Moderate P-gp in non-proliferating vessels; loss in proliferating vessels indicates transition toward BBTB.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "medium", "disease": "Astrocytoma, IDH-mutant, grade 3", "glycan_involvement": "Glycosylation affects CD146-mediated signaling.", "mechanism": "Moderate CD146 in tumor cells and non-proliferating vessels reflects intermediate grade and partial endothelial dedifferentiation.", "protein": "CD146 (MCAM/MUC18)", "protein_enriched": { "function": "Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873)", "gene_name": "ANAPC4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UJX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12486580" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Lf glycosylation facilitates receptor binding and BBB transport.", "mechanism": "Lf-modified nanoparticles enhance delivery of dopamine and rotigotine to the brain via Lf receptor-mediated transcytosis.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Lf glycosylation is essential for receptor recognition at BBB.", "mechanism": "Lf-modified nanoparticles improve delivery of huperzine to the brain for AD treatment.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tf glycosylation required for receptor-mediated transcytosis.", "mechanism": "Tf-modified liposomal nanoparticles deliver ApoE2 plasmid to the brain, inducing ApoE expression and potentially reducing AD pathology.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is glycosylated; glycosylation may affect processing and aggregation.", "mechanism": "Abnormal cleavage and aggregation of APP leads to amyloid beta plaque formation, a hallmark of AD.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12486933" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation; glycan-targeted delivery (e.g., RVG-modified NPs) used for gene silencing.", "mechanism": "Aggregation of misfolded alpha-synuclein forms Lewy bodies, contributing to PD neurodegeneration.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC12486933" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Tau can be O-glycosylated; glycosylation may modulate aggregation.", "mechanism": "Hyperphosphorylation and aggregation of tau protein leads to neurofibrillary tangles and neurodegeneration in AD.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12486933" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE glycosylation affects receptor interactions and lipid transport.", "mechanism": "ApoE2 gene delivery via Tf-modified liposomes increases ApoE expression, potentially protective in AD.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "RVG glycosylation mediates receptor binding for BBB crossing.", "mechanism": "RVG-modified nanoparticles deliver siRNA to suppress alpha-synuclein gene expression in PD.", "protein": "Rabies virus glycoprotein (RVG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation enhances BBB penetration.", "mechanism": "O-glycosylated g7 peptide facilitates nanoparticle transport into the brain for AD therapy.", "protein": "G7 peptide (O-glycosylated)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Leptin glycosylation required for receptor binding and transport.", "mechanism": "Leptin receptor-mediated transcytosis used for peptide/protein nanoparticle delivery in AD models.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12486933" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "AQP4 localization depends on glycan-mediated anchoring via \u03b2-DG.", "mechanism": "AQP4 depolarization disrupts glymphatic system function, exacerbating cerebral edema after stroke.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "\u03b2-DG is a glycoprotein; its glycosylation is essential for membrane anchoring and interaction with AQP4.", "mechanism": "\u03b2-DG degradation impairs AQP4 anchoring, leading to AQP4 depolarization and glymphatic dysfunction.", "protein": "\u03b2-dystroglycan (\u03b2-DG)", "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "MMP9 cleaves glycosylated \u03b2-DG, affecting its function.", "mechanism": "MMP9 upregulation leads to \u03b2-DG cleavage, disrupting AQP4 localization and promoting edema.", "protein": "Matrix metalloproteinase-9 (MMP9)", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (By", "gene_name": "Mmp9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P50282" }, "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Cerebral edema", "glycan_involvement": "Glycan-mediated anchoring via \u03b2-DG is required for polarized AQP4 distribution.", "mechanism": "AQP4 depolarization impairs water homeostasis, contributing to edema formation.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Cerebral edema", "glycan_involvement": "Glycosylation of \u03b2-DG is critical for its anchoring function.", "mechanism": "Loss of \u03b2-DG leads to AQP4 mislocalization and impaired water clearance.", "protein": "\u03b2-dystroglycan (\u03b2-DG)", "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Anchoring via glycosylated \u03b2-DG is disrupted in disease.", "mechanism": "AQP4 mislocalization is associated with glymphatic dysfunction and cognitive impairment.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12488257" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycan-mediated anchoring via \u03b2-DG is affected.", "mechanism": "AQP4 mislocalization correlates with glymphatic impairment and neurodegeneration.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Glymphatic system dysfunction", "glycan_involvement": "Targets glycosylated \u03b2-DG for degradation.", "mechanism": "MMP9-mediated \u03b2-DG cleavage disrupts AQP4 polarization, impairing glymphatic clearance.", "protein": "Matrix metalloproteinase-9 (MMP9)", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (By", "gene_name": "Mmp9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P50282" }, "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Glymphatic system dysfunction", "glycan_involvement": "Glycosylation required for \u03b2-DG function.", "mechanism": "Reduced \u03b2-DG impairs AQP4 anchoring, leading to glymphatic failure.", "protein": "\u03b2-dystroglycan (\u03b2-DG)", "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Glymphatic system dysfunction", "glycan_involvement": "Dependent on glycan-mediated anchoring via \u03b2-DG.", "mechanism": "AQP4 depolarization impairs GS-mediated waste clearance.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12488257" }, { "confidence": "high", "disease": "Minimal Change Disease", "glycan_involvement": "Nephrin glycosylation is mentioned as a PTM regulating its function.", "mechanism": "Autoantibodies against nephrin cause podocyte injury and proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation may affect nephrin antigenicity and immune recognition.", "mechanism": "Rituximab reduces anti-nephrin antibodies, leading to remission.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation status may influence antibody binding.", "mechanism": "Circulating anti-nephrin antibodies correlate with disease activity.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "biomarker", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation is one of several PTMs regulating nephrin.", "mechanism": "SUMOylation of nephrin maintains its stability and surface expression; inhibition leads to proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Pemphigus", "glycan_involvement": "Desmoglein-1 is a glycoprotein; glycosylation may affect its immunogenicity.", "mechanism": "Autoantibodies target desmoglein-1, causing loss of cell adhesion and blistering.", "protein": "Desmoglein-1", "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "medium", "disease": "Pemphigus", "glycan_involvement": "Glycosylation is implied as part of PTMs affecting desmoglein-1.", "mechanism": "SUMOylation regulates desmoglein-1 stability and localization; impaired SUMOylation may contribute to disease.", "protein": "Desmoglein-1", "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "medium", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation changes may create immunogenic neo-epitopes.", "mechanism": "Aberrant PTMs (including glycosylation) may unmask neo-epitopes, triggering autoimmunity.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation is one of the PTMs involved.", "mechanism": "Mutations at SUMOylation sites reduce nephrin stability and surface expression, leading to proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "medium", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation may affect nephrin localization.", "mechanism": "Redistribution and reduced density of nephrin in podocytes observed in MCD biopsies.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "biomarker", "source_pmcid": "PMC12488451" }, { "confidence": "medium", "disease": "Minimal Change Disease", "glycan_involvement": "Glycosylation is dynamically regulated and may be affected by stress.", "mechanism": "Environmental/inflammatory stimuli may alter nephrin SUMOylation and glycosylation, contributing to disease.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC12488451" }, { "confidence": "high", "disease": "Catel\u2013Manzke syndrome", "glycan_involvement": "Defective GAG biosynthesis due to reduced UDP-xylose production.", "mechanism": "TGDS deficiency leads to loss of UDP-4-keto-6-deoxyglucose, causing functional inactivation of UXS1 and impaired glycosaminoglycan (GAG) synthesis.", "protein": "TGDS", "relationship_type": "causal", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "Catel\u2013Manzke syndrome", "glycan_involvement": "Impaired initiation of GAG and O-mannosyl glycan synthesis.", "mechanism": "Functional inactivation of UXS1 due to lack of rescue metabolite from TGDS impairs UDP-xylose synthesis.", "protein": "UXS1", "relationship_type": "causal (secondary)", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "Catel\u2013Manzke syndrome", "glycan_involvement": "Defective GAG chains on proteoglycans.", "mechanism": "Reduced UDP-xylose leads to decreased heparan sulfate GAG synthesis.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal (downstream)", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "Catel\u2013Manzke syndrome", "glycan_involvement": "Defective O-mannosyl glycosylation (matriglycan).", "mechanism": "Reduced UDP-xylose impairs matriglycan (glucuronate-xylose repeat) synthesis on \u03b1-dystroglycan.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (downstream)", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "Congenital muscular dystrophy (\u03b1-dystroglycanopathy)", "glycan_involvement": "Defective matriglycan formation on \u03b1-dystroglycan.", "mechanism": "UXS1 deficiency leads to loss of UDP-xylose, impairing \u03b1-dystroglycan glycosylation.", "protein": "UXS1", "relationship_type": "causal", "source_pmcid": "PMC12488480" }, { "confidence": "medium", "disease": "Temtamy preaxial brachydactyly syndrome", "glycan_involvement": "Impaired GAG biosynthesis.", "mechanism": "TGDS deficiency phenocopies GAG synthesis disorders such as Temtamy syndrome.", "protein": "TGDS", "relationship_type": "phenotypic overlap", "source_pmcid": "PMC12488480" }, { "confidence": "medium", "disease": "Chondrodysplasia with joint dislocations, gPAPP type", "glycan_involvement": "Impaired GAG biosynthesis.", "mechanism": "TGDS deficiency shows clinical overlap with GAG synthesis disorders.", "protein": "TGDS", "relationship_type": "phenotypic overlap", "source_pmcid": "PMC12488480" }, { "confidence": "medium", "disease": "Desbuquois dysplasia", "glycan_involvement": "Impaired GAG biosynthesis.", "mechanism": "TGDS deficiency mimics GAG-related skeletal dysplasias.", "protein": "TGDS", "relationship_type": "phenotypic overlap", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "Catel\u2013Manzke syndrome", "glycan_involvement": "Indirectly affects GAG and glycoprotein synthesis via UXS1 activity.", "mechanism": "High H6PD activity lowers NAD+ in ER/Golgi, making UXS1 dependent on TGDS for reactivation.", "protein": "H6PD", "protein_enriched": { "function": "Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis ", "gene_name": "H6PD", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G14669DU", "G28681TP", "G35029YA", "G39188ZX", "G57317CE", "G60145BJ", "G80920RR", "G92050GC", "G02886BB", "G05049YU", "G15664MX", "G36442WJ", "G46691LC", "G49018RC", "G62765YT", "G70619PT", "G72747WU", "G90659AW", "G49108TO" ], "uniprot_id": "O95479" }, "relationship_type": "modulator", "source_pmcid": "PMC12488480" }, { "confidence": "medium", "disease": "Congenital muscular dystrophy (\u03b1-dystroglycanopathy)", "glycan_involvement": "Defective O-mannosyl glycosylation (matriglycan).", "mechanism": "TGDS deficiency reduces matriglycan on \u03b1-dystroglycan, a mechanism relevant to dystroglycanopathies.", "protein": "TGDS", "relationship_type": "potential causal", "source_pmcid": "PMC12488480" }, { "confidence": "high", "disease": "PMM2-CDG (Phosphomannomutase 2-Congenital Disorder of Glycosylation)", "glycan_involvement": "N-glycosylation at four sites; altered high-mannose N-glycans impact receptor processing and function.", "mechanism": "Defective N-glycosylation alters TNFR1 structure, shedding, and signaling, leading to immune dysfunction.", "protein": "TNF Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Defective N-glycosylation impairs receptor clustering and adaptor recruitment.", "mechanism": "Impaired TNFR1 glycosylation disrupts downstream signaling (MAPK, JNK, ERK1/2), reducing cytokine secretion.", "protein": "TNF Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Altered N-glycosylation reduces TACE-mediated shedding.", "mechanism": "Reduced TNFR1 shedding increases membrane-bound receptor, heightening sensitivity to TNF-\u03b1 and proinflammatory state.", "protein": "TNF Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Indirect; downstream of TNFR1 signaling affected by glycosylation.", "mechanism": "Diminished IL-6 secretion upon TNF-\u03b1 stimulation in PMM2-CDG fibroblasts indicates impaired immune activation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Indirect; reflects defective TNFR1 signaling due to glycosylation defects.", "mechanism": "Reduced CCL5 secretion in PMM2-CDG fibroblasts impairs immune cell recruitment.", "protein": "C-C Motif Chemokine Ligand 5 (CCL5)", "relationship_type": "biomarker", "source_pmcid": "PMC12488661" }, { "confidence": "medium", "disease": "PMM2-CDG (Phosphomannomutase 2-Congenital Disorder of Glycosylation)", "glycan_involvement": "Downstream of TNFR1; affected by receptor glycosylation status.", "mechanism": "Reduced expression and activation in PMM2-CDG fibroblasts, leading to impaired inflammatory response.", "protein": "p38 MAPK", "protein_enriched": { "function": "Able to phosphorylate several exogenous substrates and to undergo autophosphorylation (PubMed:10421840). Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner (PubMed:2524", "gene_name": "Mok", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G55420XE", "G63703BK" ], "uniprot_id": "Q9WVS4" }, "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "medium", "disease": "PMM2-CDG (Phosphomannomutase 2-Congenital Disorder of Glycosylation)", "glycan_involvement": "Downstream of TNFR1; affected by glycosylation defects.", "mechanism": "Nearly undetectable in PMM2-CDG fibroblasts, contributing to defective cytokine expression.", "protein": "c-Jun N-terminal kinase 2 (JNK2)", "protein_enriched": { "function": "Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed", "gene_name": "MAPK9", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G46687AB", "G49108TO" ], "uniprot_id": "P45984" }, "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "medium", "disease": "Stroke-like episodes", "glycan_involvement": "Defective N-glycosylation increases proinflammatory signaling.", "mechanism": "Altered TNFR1 signaling may exacerbate neuroinflammation and blood-brain barrier permeability during infection-triggered episodes.", "protein": "TNF Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Recurrent infections", "glycan_involvement": "N-glycosylation defects disrupt receptor function.", "mechanism": "Impaired TNFR1 signaling leads to reduced cytokine/chemokine secretion, weakening immune defense.", "protein": "TNF Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "medium", "disease": "PMM2-CDG (Phosphomannomutase 2-Congenital Disorder of Glycosylation)", "glycan_involvement": "Indirect; reflects altered TNFR1 glycosylation.", "mechanism": "Failure to upregulate TRAF5 in PMM2-CDG fibroblasts impairs TNFR1 downstream signaling.", "protein": "TRAF5", "protein_enriched": { "function": "Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. M", "gene_name": "TRAF5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00463" }, "relationship_type": "causal", "source_pmcid": "PMC12488661" }, { "confidence": "high", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation modulates IL-6 stability and receptor binding.", "mechanism": "Elevated plasma IL-6 correlates with disease severity and systemic inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "high", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation affects TNF-\u03b1 secretion and bioactivity.", "mechanism": "Increased TNF-\u03b1 levels indicate active inflammation.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation required for proper folding and secretion.", "mechanism": "IL-1\u03b2 elevation reflects cutaneous and systemic inflammation.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation influences anti-inflammatory activity.", "mechanism": "IL-10 upregulation may counteract inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation affects receptor interaction.", "mechanism": "IL-17A is associated with chronic skin inflammation.", "protein": "Interleukin-17A (IL-17A)", "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "high", "disease": "Early kidney injury", "glycan_involvement": "N-glycosylation modulates renal inflammatory signaling.", "mechanism": "IL-6 elevation predicts renal injury in PN patients.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation essential for CRP function.", "mechanism": "CRP levels reflect systemic inflammatory burden.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation modulates chemotactic activity.", "mechanism": "CXCL8 elevation indicates neutrophil recruitment.", "protein": "Interleukin-8 (CXCL8)", "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Early kidney injury", "glycan_involvement": "N-glycosylation critical for EPO stability and activity.", "mechanism": "Altered EPO levels signal renal dysfunction.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "medium", "disease": "Prurigo nodularis", "glycan_involvement": "N-glycosylation affects cytokine signaling.", "mechanism": "IL-13 upregulation linked to Th2-driven inflammation.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "biomarker", "source_pmcid": "PMC12489339" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and receptor binding.", "mechanism": "High insulin levels promote cancer cell proliferation and progression.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "IGF-1 glycosylation modulates receptor interaction and bioactivity.", "mechanism": "Elevated IGF-1 stimulates tumor growth and metastasis.", "protein": "IGF-1 (Insulin-like Growth Factor 1)", "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Overexpression increases glucose uptake, supporting tumor metabolism.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12490225" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "N-glycosylation affects trafficking and activity.", "mechanism": "Upregulated in tumors, facilitating glucose uptake.", "protein": "GLUT3 (SLC2A3)", "relationship_type": "biomarker", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation essential for proper function.", "mechanism": "Impaired GLUT4 function leads to insulin resistance.", "protein": "GLUT4 (SLC2A4)", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of", "gene_name": "SLC2A4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P14672" }, "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Cardiotoxicity (therapy-induced)", "glycan_involvement": "HER2 is glycosylated; glycosylation modulates antibody binding and receptor stability.", "mechanism": "Trastuzumab targets HER2, disrupting cardiac signaling and causing dysfunction.", "protein": "HER2/ERBB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12490225" }, { "confidence": "medium", "disease": "Cardiometabolic Syndrome", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "VEGF promotes angiogenesis and vascular remodeling in metabolic disease.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "medium", "disease": "Cardiotoxicity (therapy-induced)", "glycan_involvement": "Glycosylation affects PDGF receptor interaction.", "mechanism": "PDGF inhibitors cause hypertension and mild cardiomyopathy.", "protein": "PDGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "N-glycosylation required for LDL binding and receptor function.", "mechanism": "LDLR deficiency leads to elevated cholesterol and cardiovascular risk.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "O-GlcNAcylation of cardiac proteins modulates contractility and stress response.", "mechanism": "Increased O-GlcNAc modification in failing heart alters protein function and signaling.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12490225" }, { "confidence": "high", "disease": "Non-ischemic Heart Failure", "glycan_involvement": "FAP is a glycoprotein; glycosylation is required for its cell surface expression and enzymatic activity.", "mechanism": "FAP is upregulated on activated myocardial fibroblasts, marking early fibrotic activity and correlating with disease severity and poor functional improvement.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12490530" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Glycosylation of FAP modulates its stability and function in ECM remodeling.", "mechanism": "FAP expression is highest in DCM among non-ischemic HF etiologies, reflecting chronic fibroblast activation and diffuse fibrosis.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12490530" }, { "confidence": "high", "disease": "Heart Failure with Reduced Ejection Fraction (HFrEF)", "glycan_involvement": "FAP glycosylation supports its role in fibroblast activation and ECM degradation.", "mechanism": "Higher FAP activity correlates with lower LVEF and more severe myocardial dysfunction.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12490530" }, { "confidence": "medium", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "As above.", "mechanism": "FAP activity is elevated but lower than in HFrEF, reflecting less extensive fibroblast activation.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12490530" }, { "confidence": "high", "disease": "Non-ischemic Heart Failure", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation is essential for secretion and receptor binding.", "mechanism": "TGF-\u03b21 signaling drives fibroblast activation and ECM synthesis, promoting fibrosis.", "protein": "Transforming Growth Factor-beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12490530" }, { "confidence": "high", "disease": "Non-ischemic Heart Failure", "glycan_involvement": "Collagen is glycosylated, affecting fibril formation and ECM structure.", "mechanism": "Excessive type I collagen deposition by activated fibroblasts stiffens myocardium, leading to dysfunction.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12490530" }, { "confidence": "medium", "disease": "Heart Failure with Preserved Ejection Fraction (HFpEF)", "glycan_involvement": "Glycosylation modulates collagen fiber assembly.", "mechanism": "Relative deficiency of type III collagen increases myocardial stiffness in HFpEF.", "protein": "Type III Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12490530" }, { "confidence": "medium", "disease": "Acute Myocarditis", "glycan_involvement": "As above.", "mechanism": "FAP activity is lower in acute myocarditis, reflecting less fibroblast-mediated fibrosis in early inflammatory phase.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12490530" }, { "confidence": "medium", "disease": "Hypertensive Heart Disease", "glycan_involvement": "As above.", "mechanism": "FAP activity is present but lower than in DCM, reflecting interstitial rather than diffuse fibrosis.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12490530" }, { "confidence": "medium", "disease": "Non-ischemic Heart Failure", "glycan_involvement": "Not a glycoprotein; included for context.", "mechanism": "Upregulated in activated myofibroblasts, contributing to ECM remodeling and fibrosis.", "protein": "\u03b1-Smooth Muscle Actin (\u03b1-SMA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12490530" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation is essential for LRG's stability and serum detection.", "mechanism": "LRG reflects endoscopic and inflammatory activity in UC, induced by cytokines (IL-22, TNF-\u03b1, IL-1\u03b2) independent of IL-6.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Serum glycosylation enables LRG's biomarker function.", "mechanism": "LRG is elevated in RA due to systemic inflammation.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "medium", "disease": "Infections", "glycan_involvement": "Glycosylation supports LRG's secretion and stability.", "mechanism": "LRG is upregulated in response to infection-induced cytokines.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "medium", "disease": "Malignant diseases", "glycan_involvement": "Glycosylation is required for LRG's serum presence.", "mechanism": "LRG is elevated in various cancers, reflecting systemic inflammation.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation allows LRG quantification in serum.", "mechanism": "LRG levels are suppressed by corticosteroids, calcineurin inhibitors, JAK inhibitors, and anti-TNF-\u03b1 agents, even during mucosal healing.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation is necessary for LRG's function as a biomarker.", "mechanism": "LRG levels are increased by vedolizumab and interleukin-23 receptor antagonists, possibly due to lack of direct cytokine suppression.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation enables LRG's serum stability.", "mechanism": "LRG remains a useful biomarker in CRP-negative UC patients.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation is required for LRG's detection.", "mechanism": "LRG levels correlate with endoscopic activity (Mayo Endoscopic Subscore).", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation supports LRG's serum function.", "mechanism": "LRG is a nonspecific biomarker and may be confounded by comorbidities (e.g., infection, cancer).", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation is essential for LRG's secretion and function.", "mechanism": "LRG induction is mediated by cytokines (IL-22, TNF-\u03b1, IL-1\u03b2) via JAK/STAT and NF-\u03baB pathways.", "protein": "Leucine-rich alpha-2 glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12490836" }, { "confidence": "high", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "HHL is not a glycoprotein but is degraded by glycoprotein-rich probiotic strains.", "mechanism": "HHL regulates virulence gene expression in Aeromonas hydrophila.", "protein": "N-hexanoyl homoserine lactone (HHL)", "relationship_type": "causal", "source_pmcid": "PMC12492942" }, { "confidence": "high", "disease": "Fish gut dysbiosis", "glycan_involvement": "Glycan diversity mediates lectin interactions for gut colonization.", "mechanism": "Glycoprotein diversity enhances probiotic adhesion and colonization, restoring gut microbiota balance.", "protein": "Bacterial surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "medium", "disease": "Vibrio spp. infection", "glycan_involvement": "Specific glycan fingerprints enable competitive binding to host lectins.", "mechanism": "Lectin-glycan interactions facilitate probiotic exclusion of Vibrio spp. from gut epithelium.", "protein": "Lectin-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "medium", "disease": "Edwardsiella spp. infection", "glycan_involvement": "Mannosylation promotes lectin-mediated immune activation.", "mechanism": "Mannose-rich glycoproteins on probiotics interact with host MBL, enhancing immune response against pathogens.", "protein": "Mannose-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "low", "disease": "Biofilm-associated disease", "glycan_involvement": "Sialylation affects lectin recognition and biofilm stability.", "mechanism": "Sialylated glycoproteins modulate biofilm formation and immune evasion.", "protein": "Sialic acid-binding glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12492942" }, { "confidence": "medium", "disease": "Antibiotic resistance", "glycan_involvement": "Glycan-mediated exclusion of resistant pathogens.", "mechanism": "Probiotic glycoprotein diversity reduces pathogen colonization, limiting antibiotic resistance gene spread.", "protein": "Bacterial surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "high", "disease": "Vibrio spp. infection", "glycan_involvement": "Degradation by glycoprotein-rich probiotics interrupts QS signaling.", "mechanism": "HHL regulates virulence and biofilm formation in Vibrio spp.", "protein": "N-hexanoyl homoserine lactone (HHL)", "relationship_type": "causal", "source_pmcid": "PMC12492942" }, { "confidence": "high", "disease": "Fish gut dysbiosis", "glycan_involvement": "Glycosylation patterns determine lectin binding and colonization efficiency.", "mechanism": "Lectin-glycan interactions promote probiotic colonization and microbiota restoration.", "protein": "Lectin-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "medium", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "Galactosylation enhances host-probiotic interaction.", "mechanism": "Galactosylated glycoproteins facilitate competitive exclusion of pathogens via lectin binding.", "protein": "Galactose-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12492942" }, { "confidence": "medium", "disease": "Biofilm-associated disease", "glycan_involvement": "Glycan modifications alter biofilm stability and immune recognition.", "mechanism": "Glycoprotein architecture influences biofilm formation and pathogen persistence.", "protein": "Bacterial surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12492942" }, { "confidence": "high", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "Mediates sialylation of O-glycans on neuronal proteins.", "mechanism": "Downregulation in mPFC induces depressive-like behaviors; overexpression reverses symptoms.", "protein": "ST3GAL1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Regulates O-glycan sialylation in PFC; altered in MDD.", "mechanism": "Genetic association and functional studies suggest ST3GAL1 as a target for MDD intervention.", "protein": "ST3GAL1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12494006" }, { "confidence": "high", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "ST3GAL1-dependent O-glycan sialylation at T1584; restored by St3gal1 overexpression.", "mechanism": "Loss of O-glycan sialylation at T1584 under stress destabilizes GABAergic synapses, contributing to depressive-like behaviors.", "protein": "NRXN2 (Neurexin 2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "O-glycan sialylation at T159 site.", "mechanism": "Sialylated O-glycosylation lost under stress, restored by St3gal1 overexpression.", "protein": "DNER", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "O-glycan sialylation at T338 site.", "mechanism": "Sialylated O-glycosylation lost under stress, restored by St3gal1 overexpression.", "protein": "OMGP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "O-glycan sialylation at S304 site.", "mechanism": "Sialylated O-glycosylation lost under stress, restored by St3gal1 overexpression.", "protein": "CSPG5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "O-glycan sialylation at T776 site.", "mechanism": "Sialylated O-glycosylation lost under stress, restored by St3gal1 overexpression.", "protein": "LRRK2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Depressive-like behaviors (mouse model)", "glycan_involvement": "Indirectly regulated via ST3GAL1 pathway.", "mechanism": "Upregulated by stress, reversed by St3gal1 overexpression; involved in synaptic plasticity and stress response.", "protein": "MERTK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "downstream effector", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Bipolar disorder", "glycan_involvement": "O-glycan sialylation in brain regions.", "mechanism": "GWAS links ST3GAL1 to bipolar disorder risk and symptom severity.", "protein": "ST3GAL1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12494006" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "O-glycan sialylation in brain regions.", "mechanism": "GWAS and transcriptomics link ST3GAL1 to schizophrenia functional impairments.", "protein": "ST3GAL1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12494006" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation affects PSA detection and specificity.", "mechanism": "PSA glycosylation patterns are used for cancer screening and diagnosis.", "protein": "PSA (Prostate-specific antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12494505" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation is essential for antigenicity and detection.", "mechanism": "CA125 glycosylation is clinically used for ovarian cancer diagnosis.", "protein": "CA125 (Cancer antigen 125)", "relationship_type": "biomarker", "source_pmcid": "PMC12494505" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycan structure determines antigen specificity.", "mechanism": "CA19-9 glycosylation is used for pancreatic cancer screening.", "protein": "CA19-9 (Carbohydrate antigen 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12494505" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "Glycosylation affects AFP detection and function.", "mechanism": "AFP glycosylation is used for liver cancer diagnosis.", "protein": "AFP (Alpha-fetoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "Sialylated N-glycans on glycoRNA act as ligands for Siglec-10.", "mechanism": "GlycoRNAs bind Siglec-10, modulating immune checkpoint and tumor immune evasion.", "protein": "Siglec-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Immune checkpoint regulation", "glycan_involvement": "Sialylated N-glycans mediate binding.", "mechanism": "GlycoRNAs interact with Siglec-11, influencing immune checkpoint signaling.", "protein": "Siglec-11", "protein_enriched": { "function": "Uniporter that mediates the uptake of cationic L-amino acids such as L-arginine, L-lysine and L-ornithine (PubMed:11591158). The transport is sodium ions- and pH-independent, moderately trans-stimulat", "gene_name": "SLC7A3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8WY07" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation of RNA enables P-selectin binding.", "mechanism": "GlycoRNAs interact with P-selectin, enhancing neutrophil recruitment to inflammatory sites.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Cell adhesion disorders", "glycan_involvement": "Glycosylation may affect RNA localization and function.", "mechanism": "Membrane-localized FNDC3B RNA fragments regulate cell adhesion to endothelial cells.", "protein": "FNDC3B", "protein_enriched": { "function": "Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine (PubMed:23912683, PubMed:23912718, PubMed:25195743, PubMed:27573237, Pub", "gene_name": "ENDOV", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N8Q3" }, "relationship_type": "causal", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Cell adhesion disorders", "glycan_involvement": "Glycosylation may influence RNA-protein interactions.", "mechanism": "Membrane-localized CTSS RNA fragments modulate cell adhesion.", "protein": "CTSS (Cathepsin S)", "protein_enriched": { "function": "Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules and MHC class II antigen presentation (PubMed:30612035). The bond-specificity of this protei", "gene_name": "CTSS", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P25774" }, "relationship_type": "causal", "source_pmcid": "PMC12494505" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation of RNA regulates cell surface presentation and metastatic potential.", "mechanism": "Higher glycoRNA levels on cell surface inversely correlate with breast cancer malignancy and metastasis.", "protein": "GlycoRNA (general)", "relationship_type": "protective", "source_pmcid": "PMC12494505" }, { "confidence": "high", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "EGFR is a transmembrane glycoprotein; glycosylation affects ligand binding and receptor activation.", "mechanism": "EGFR overexpression and phosphorylation drive proliferation and migration in ATC; targeted by kinase inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12495765" }, { "confidence": "high", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "VEGFR-2 is a glycoprotein; glycosylation modulates receptor dimerization and signaling.", "mechanism": "VEGFR-2 overexpression promotes angiogenesis and tumor progression; targeted by anti-angiogenic drugs.", "protein": "VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12495765" }, { "confidence": "high", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "CXCR4 is a glycoprotein; glycosylation influences receptor trafficking and ligand binding.", "mechanism": "CXCR4 activation enhances kinase cascades (ERK1/2, Akt), promoting proliferation and migration.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "JAM-A is a glycoprotein; glycosylation may affect cell adhesion and migration.", "mechanism": "JAM-A downregulation in ATC; overexpression increases phosphorylation of p53/GSK3\u03b1/\u03b2 and inhibits migration.", "protein": "JAM-A", "relationship_type": "protective", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "IGFBP7 is a secreted glycoprotein; glycosylation may affect stability and IGF binding.", "mechanism": "IGFBP7 loss in ATC; overexpression inhibits growth via cell cycle arrest and reduced Akt/Rb phosphorylation.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12495765" }, { "confidence": "high", "disease": "De-differentiated thyroid carcinoma", "glycan_involvement": "CD44 is a heavily glycosylated cell surface protein; glycosylation modulates ligand interactions and migration.", "mechanism": "CD44 upregulation marks stemness and EMT in ATC; regulated by SUMOylated TFAP2A.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "SUMOylation is not a glycan modification, but TFAP2A regulates glycoprotein CD44.", "mechanism": "SUMOylation of TFAP2A increases CD44 expression, promoting proliferation and de-differentiation.", "protein": "TFAP2A", "protein_enriched": { "function": "Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCC", "gene_name": "TFAP2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05549" }, "relationship_type": "causal", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "KLHL14 has glycoprotein-like domains; glycosylation status not specified.", "mechanism": "KLHL14 downregulation is an early marker of de-differentiation in ATC.", "protein": "KLHL14", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "ISG15 is a ubiquitin-like modifier; not a glycan, but modifies glycoprotein KPNA2.", "mechanism": "ISG15-mediated ISGylation of KPNA2 enhances stemness and growth, reduces drug sensitivity.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "causal", "source_pmcid": "PMC12495765" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "KPNA2 is a nuclear import protein; glycosylation status not specified.", "mechanism": "ISGylation of KPNA2 prevents its ubiquitin-mediated degradation, promoting nuclear translocation of c-MYC and stemness gene expression.", "protein": "KPNA2", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "KPNA6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60684" }, "relationship_type": "causal", "source_pmcid": "PMC12495765" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Cystatin C is N-glycosylated, which affects its stability and serum half-life.", "mechanism": "Serum cystatin C levels inversely reflect muscle mass; higher cystatin C indicates lower muscle mass (sarcopenia).", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "high", "disease": "Ventricular Arrhythmia", "glycan_involvement": "N-glycosylation may influence cystatin C's serum levels and detection.", "mechanism": "Elevated cystatin C (as part of low sarcopenia index) predicts increased risk of ventricular arrhythmia in diabetic patients.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "medium", "disease": "Ventricular Arrhythmia", "glycan_involvement": "NT-proBNP is glycosylated, which affects its stability and clearance.", "mechanism": "Higher NT-proBNP levels are associated with worse cardiac function and increased arrhythmia risk.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "medium", "disease": "Ventricular Arrhythmia", "glycan_involvement": "CRP is glycosylated; glycosylation affects its function and clearance.", "mechanism": "Elevated hs-CRP (inflammation marker) correlates with increased risk of ventricular arrhythmia.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "N-glycosylation affects cystatin C's serum stability.", "mechanism": "Cystatin C is used in the sarcopenia index to assess muscle mass in T2DM patients.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "medium", "disease": "Sudden Cardiac Death", "glycan_involvement": "N-glycosylation may affect cystatin C's diagnostic utility.", "mechanism": "Low sarcopenia index (high cystatin C/low creatinine) predicts higher risk of sudden cardiac death in T2DM.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated hs-CRP reflects chronic inflammation in T2DM.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12495775" }, { "confidence": "high", "disease": "Tumefactive demyelinating lesions (TDLs)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "MOG antibodies identify an inflammatory TDLs variant with increased CSF WCC and better lesion recovery.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12496048" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG influences immune recognition.", "mechanism": "Autoantibodies against MOG cause demyelination in MOGAD, sometimes presenting as TDLs.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12496048" }, { "confidence": "high", "disease": "NMDAR encephalitis", "glycan_involvement": "NMDAR is glycosylated; glycan structures may modulate antibody access.", "mechanism": "Autoantibodies against NMDAR cause neuropsychiatric symptoms and demyelinating lesions.", "protein": "N-methyl-D-aspartate receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12496048" }, { "confidence": "medium", "disease": "Tumefactive demyelinating lesions (TDLs)", "glycan_involvement": "Glycosylation may affect NMDAR antigenicity.", "mechanism": "NMDAR antibodies mark TDLs cases with elevated systemic inflammation and younger onset.", "protein": "N-methyl-D-aspartate receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12496048" }, { "confidence": "medium", "disease": "MNOS (MOG and NMDAR antibody-associated overlapping syndrome)", "glycan_involvement": "MOG glycosylation may influence dual antibody response.", "mechanism": "MOG antibodies co-occur with NMDAR antibodies in MNOS, indicating overlapping autoimmune pathology.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12496048" }, { "confidence": "medium", "disease": "MNOS (MOG and NMDAR antibody-associated overlapping syndrome)", "glycan_involvement": "NMDAR glycosylation may modulate immune recognition.", "mechanism": "NMDAR antibodies co-occur with MOG antibodies in MNOS, reflecting shared or sequential immune targeting.", "protein": "N-methyl-D-aspartate receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12496048" }, { "confidence": "medium", "disease": "Tumefactive demyelinating lesions (TDLs)", "glycan_involvement": "Glycosylation may affect MOG's immunogenicity and therapeutic response.", "mechanism": "MOG+ TDLs respond well to immunotherapy, with robust lesion recovery.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12496048" }, { "confidence": "medium", "disease": "Tumefactive demyelinating lesions (TDLs)", "glycan_involvement": "Glycosylation may influence antibody binding and treatment efficacy.", "mechanism": "NMDAR+ TDLs are more likely to receive immunomodulatory treatment.", "protein": "N-methyl-D-aspartate receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12496048" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG trigger inflammatory demyelination of optic nerves.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12497580" }, { "confidence": "medium", "disease": "Retinal hemorrhage", "glycan_involvement": "Glycosylation of MOG may influence immune response and vascular inflammation.", "mechanism": "MOG-ON may cause optic disc edema leading to impaired retinal venous outflow and hemorrhage.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal/associated", "source_pmcid": "PMC12497580" }, { "confidence": "medium", "disease": "Roth spots", "glycan_involvement": "Glycosylation may modulate MOG's immunogenicity, contributing to vascular inflammation.", "mechanism": "Vascular inflammation in MOG-ON may result in Roth spots as a secondary manifestation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "associated", "source_pmcid": "PMC12497580" }, { "confidence": "high", "disease": "Allergic asthma", "glycan_involvement": "Phosphorylation status (glycosylation-related PTM) regulates function.", "mechanism": "OPN promotes eosinophil migration in airways; increased expression in asthma.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "high", "disease": "Allergic asthma", "glycan_involvement": "Regulates OPN phosphorylation, impacting glycoprotein function.", "mechanism": "TRAP5 dephosphorylates OPN, facilitating eosinophil migration and amplifying inflammation.", "protein": "TRAP5/ACP5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12498364" }, { "confidence": "high", "disease": "Allergic asthma", "glycan_involvement": "Heavily O-glycosylated; glycosylation affects mucus properties.", "mechanism": "MUC5AC levels increase with airway inflammation and mucus production.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12498364" }, { "confidence": "medium", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation modulates extracellular matrix interactions.", "mechanism": "Periostin associated with eosinophil infiltration and airway remodeling.", "protein": "Periostin", "relationship_type": "biomarker", "source_pmcid": "PMC12498364" }, { "confidence": "medium", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation may affect cytokine stability and signaling.", "mechanism": "IL-33 mediates early Type 2 immune response and eosinophil survival.", "protein": "IL-33", "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "high", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation influences cytokine-receptor interactions.", "mechanism": "IL-5 promotes eosinophil recruitment and activation in asthma.", "protein": "IL-5", "protein_enriched": { "function": "Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:2653458, PubMed:9010276)", "gene_name": "IL5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P05113" }, "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "high", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "IL-13 drives mucus production and airway hyperresponsiveness.", "protein": "IL-13", "protein_enriched": { "function": "Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immun", "gene_name": "IL15", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P40933" }, "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "medium", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "RANTES is elevated in airway inflammation, recruiting immune cells.", "protein": "RANTES (CCL5)", "relationship_type": "biomarker", "source_pmcid": "PMC12498364" }, { "confidence": "medium", "disease": "Allergic asthma", "glycan_involvement": "Glycosylation impacts cytokine stability.", "mechanism": "GM-CSF supports eosinophil and macrophage survival in inflamed airways.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "medium", "disease": "Neutrophilic asthma", "glycan_involvement": "Phosphorylation status (glycosylation-related PTM) alters immune cell recruitment.", "mechanism": "Altered OPN phosphorylation in TRAP5-deficient mice skews inflammation toward neutrophilic profile.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12498364" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Mannan structures are major antigens recognized by host antibodies.", "mechanism": "Elicits strong IgG and IgM antibody response in infected humans and mice; antibody levels distinguish infected from non-infected individuals.", "protein": "Mannan (Candida cell wall mannan)", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "\u03b2-Glucan is initially exposed and recognized by immune system, but later shielded by mannans.", "mechanism": "Early IgM antibody response post-infection; less robust IgG response compared to mannans.", "protein": "\u03b2-Glucan (Candida cell wall \u03b2-glucan)", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive Candida spp. infection", "glycan_involvement": "Unique glycan epitope for C. krusei; not recognized in other Candida spp.", "mechanism": "IgG antibodies against this glycan are specific for C. krusei infection.", "protein": "\u03b2-(1,2)-mannose monomer", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Synthetic glycan mimics Candida surface structure, recognized by host antibodies.", "mechanism": "Elicits strong antibody response in infected humans and mice; candidate for diagnostics and vaccine development.", "protein": "Tetrasaccharide antigen (\u03b2-(1,2)Man-\u03b1-(1,2)Man-\u03b1-(1,2)Man-\u03b1-(1,2)Man)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Key mannan epitope for immune recognition.", "mechanism": "Strongly recognized by antibodies in infected humans; potential for diagnostic and vaccine use.", "protein": "Pentasaccharide antigen (\u03b1-(1,2)Man-\u03b1-(1,3)Man-\u03b1-(1,2)Man-\u03b1-(1,2)Man-\u03b1-(1,2)Man)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Synthetic \u03b2-glucan structure mimics immunodominant epitope.", "mechanism": "Identified as a lead antigen for diagnostics and vaccine development.", "protein": "\u03b2-(1,3)Glc-\u03b2-(1,3)Glc-\u03b2-(1,3)Glc-[\u03b2-(1,6)Glc]-\u03b2-(1,3)Glc", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12501125" }, { "confidence": "medium", "disease": "Invasive Candida spp. infection", "glycan_involvement": "Species-specific glycan epitopes for differential diagnosis.", "mechanism": "IgG antibodies against these structures are present in C. albicans, C. tropicalis, and C. glabrata infections, but absent in C. parapsilosis, C. lusitaniae, C. dubliniensis, and C. krusei.", "protein": "Phosphodiester-linked mannosides", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Candidemia", "glycan_involvement": "Dynamic antibody response to mannan epitopes during infection.", "mechanism": "Serum IgG against specific mannan structures (e.g., M8, M13) increases after positive blood culture.", "protein": "Mannan (Candida cell wall mannan)", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "medium", "disease": "Candidemia", "glycan_involvement": "\u03b2-Glucan antibodies present in both infected and non-infected individuals.", "mechanism": "IgG antibodies detectable before positive blood culture, but not specific for infection.", "protein": "\u03b2-Glucan (Candida cell wall \u03b2-glucan)", "relationship_type": "biomarker", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Targeting mannan structures for broad-spectrum Candida vaccine.", "mechanism": "Synthetic mannan epitopes (M8, M13) proposed for monoclonal antibody or glycoconjugate vaccine development.", "protein": "Mannan (Candida cell wall mannan)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12501125" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation critical for function and binding to ECM.", "mechanism": "Reduced expression correlates with muscle degeneration; upregulation by ARC-18 improves muscle integrity.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation modulates ECM interactions.", "mechanism": "Elevated in DMD muscle fibrosis; ARC-18 reduces fibronectin, suppressing fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation affects collagen stability and deposition.", "mechanism": "Increased in DMD fibrosis; ARC-18 reduces collagen I, limiting fibrotic progression.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12501411" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation required for ECM assembly.", "mechanism": "ARC-18 increases laminin, supporting muscle structure and regeneration.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "No direct glycosylation; acetylation is the key PTM.", "mechanism": "ACLY-mediated acetylation of Smad2/3 promotes nuclear localization and fibrosis; ARC-18 inhibits this process.", "protein": "Smad2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "No direct glycosylation.", "mechanism": "Upregulated in DMD; drives Smad2/3 acetylation and fibrosis. ARC-18 promotes ACLY degradation.", "protein": "ATP-citrate lyase (ACLY)", "protein_enriched": { "function": "Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism", "gene_name": "ACLY", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53396" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Not glycosylated.", "mechanism": "Loss causes DMD; ARC-18 upregulates dystrophin-associated proteins.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12501411" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Not glycosylated.", "mechanism": "Marker of myofibroblast conversion; reduced by ARC-18.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12501411" }, { "confidence": "medium", "disease": "Muscle atrophy", "glycan_involvement": "Not glycosylated.", "mechanism": "ARC-18 increases MHC, indicating improved muscle regeneration.", "protein": "Myosin heavy chain (MHC)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12501411" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Not glycosylated.", "mechanism": "Elevated in DMD; ARC-18 normalizes Pax7, indicating improved satellite cell function.", "protein": "Pax7", "protein_enriched": { "function": "May have regulatory role in cell division or differentiation in response to extracellular signals", "gene_name": "SKIL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12757" }, "relationship_type": "biomarker", "source_pmcid": "PMC12501411" }, { "confidence": "high", "disease": "Tumor (cancer)", "glycan_involvement": "Afucosylation at Fc N-glycan increases effector function.", "mechanism": "Afucosylated IgG1 (F0) enhances anti-tumor activity via Fc\u03b3RIII engagement.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "high", "disease": "Tumor (cancer)", "glycan_involvement": "Both de-galactosylated and galactosylated/sialylated forms are protective.", "mechanism": "IgG2a (including glycoengineered forms) mediates tumor protection via Fc\u03b3RIV and effector cell activation.", "protein": "IgG2a", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Tumor (cancer)", "glycan_involvement": "Agalactosylation enhances neutrophil-mediated cytotoxicity.", "mechanism": "IgG2b, especially in agalactosylated form, promotes neutrophil activation and tumor protection.", "protein": "IgG2b", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "high", "disease": "Tumor (cancer)", "glycan_involvement": "Subclass ratio more important than glycan modification.", "mechanism": "High IgG2c/IgG1 ratios correlate with tumor protection, likely via Fc\u03b3RIV and NK cell activation.", "protein": "IgG2c", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Tumor (cancer)", "glycan_involvement": "Afucosylation at Fc N-glycan site.", "mechanism": "Transient peaks of afucosylated IgG1 after vaccination indicate effective anti-tumor response.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Agalactosylation promotes inflammation.", "mechanism": "Low galactosylation of IgG1 is associated with Th17 responses and autoimmunity.", "protein": "IgG1", "relationship_type": "causal", "source_pmcid": "PMC12502179" }, { "confidence": "high", "disease": "Tumor (cancer)", "glycan_involvement": "Both glycoforms retain anti-tumor efficacy.", "mechanism": "Glycoengineered anti-TRP1 IgG2a mAbs (de-galactosylated or sialylated) are effective therapeutics.", "protein": "IgG2a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Tumor (cancer)", "glycan_involvement": "Afucosylation upon antigen re-exposure.", "mechanism": "Poly(I:C) and eCFA adjuvants induce memory responses with afucosylated IgG1, enhancing tumor protection.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Tumor (cancer)", "glycan_involvement": "Galactosylation and sialylation enhance NK cell activation.", "mechanism": "Di-galactosylated and sialylated IgG1 induced by Poly(I:C) promote NK cell-mediated tumor protection.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "medium", "disease": "Tumor (cancer)", "glycan_involvement": "Low galactosylation/sialylation enhances neutrophil activation.", "mechanism": "Agalactosylated/asialylated IgG1 induced by eCFA promote neutrophil-mediated tumor protection.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC12502179" }, { "confidence": "high", "disease": "Selective glomerular hypofiltration syndrome (SGHS)/Shrunken pore syndrome", "glycan_involvement": "Osteopontin is a glycoprotein; glycosylation may affect its secretion and function in inflammation.", "mechanism": "OPN is associated with higher prevalence of SGHS; may promote glomerular injury via inflammation and fibrosis.", "protein": "Osteopontin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12502603" }, { "confidence": "high", "disease": "Acute kidney failure", "glycan_involvement": "Glycosylation of OPN may modulate its pro-inflammatory activity.", "mechanism": "Elevated OPN predicts higher risk of hospitalization for acute kidney failure; may drive macrophage infiltration and fibrosis.", "protein": "Osteopontin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may regulate OPN stability and interaction with immune cells.", "mechanism": "OPN overexpression is linked to CKD progression via chronic inflammation and fibrosis.", "protein": "Osteopontin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects OPN secretion and function.", "mechanism": "OPN is elevated in HF and may reflect ongoing inflammation and fibrosis.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "Cardiorenal syndrome", "glycan_involvement": "Glycosylation modulates OPN's immune activity.", "mechanism": "OPN may mediate bidirectional dysfunction between heart and kidney via inflammation.", "protein": "Osteopontin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "Glycosylation may affect OPN's pathogenic role.", "mechanism": "OPN promotes glomerular injury; deletion reduces albuminuria and fibrosis in models.", "protein": "Osteopontin", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12502603" }, { "confidence": "high", "disease": "Selective glomerular hypofiltration syndrome (SGHS)/Shrunken pore syndrome", "glycan_involvement": "Cystatin C is a glycoprotein; glycosylation may influence filtration.", "mechanism": "Reduced filtration of cystatin C is a defining feature of SGHS.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may affect cystatin C's stability and filtration.", "mechanism": "Elevated cystatin C predicts CKD progression.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12502603" }, { "confidence": "medium", "disease": "End-stage kidney disease", "glycan_involvement": "Glycosylation may modulate OPN's pathogenicity.", "mechanism": "High OPN associated with progression to end-stage kidney disease.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12502603" }, { "confidence": "low", "disease": "Kidney transplant dysfunction", "glycan_involvement": "Glycosylation may affect OPN's immune interactions.", "mechanism": "High OPN and SGHS associated with delayed graft function and worse outcomes.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12502603" }, { "confidence": "high", "disease": "Influenza A and B infection", "glycan_involvement": "High sialylation at Asn221 site is essential for antiviral activity.", "mechanism": "Hypersialylated N-glycans at Asn221 enable strong binding to sialic acid-dependent viral receptors, inhibiting hemagglutination.", "protein": "IgG1-Fc Asn221 mutant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12503014" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Hypersialylation increases anti-inflammatory activity.", "mechanism": "Sialylated Fc glycans interact with sialic acid receptors, modulating immune responses.", "protein": "IgG1-Fc Asn221 mutant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Immunogenicity (adverse reactions)", "glycan_involvement": "NeuGc is immunogenic in humans; low levels in CHO cells reduce risk.", "mechanism": "Presence of NeuGc sialic acid in N-glycans can trigger harmful immune responses in humans.", "protein": "Monoclonal antibody (mAb)", "relationship_type": "causal", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Reduced efficacy of biopharmaceuticals", "glycan_involvement": "Variation in N-glycan branching, sialylation, and fucosylation modulates function.", "mechanism": "Glycosylation heterogeneity affects antibody effector function, serum half-life, and therapeutic efficacy.", "protein": "Monoclonal antibody (mAb)", "relationship_type": "causal", "source_pmcid": "PMC12503014" }, { "confidence": "medium", "disease": "Reduced efficacy of biopharmaceuticals", "glycan_involvement": "Sialylation and galactosylation at Asn297 impact antibody activity.", "mechanism": "Low sialylation at Asn297 site reduces anti-inflammatory and effector functions.", "protein": "IgG1-Fc Asn297", "relationship_type": "causal", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Influenza B infection", "glycan_involvement": "CHO-K1-derived hypersialylation is required for inhibition.", "mechanism": "Cell line-specific glycosylation (CHO-K1 vs HEK293) determines ability to inhibit influenza B hemagglutination.", "protein": "IgG1-Fc Asn221 mutant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12503014" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Higher sialylation increases therapeutic potential.", "mechanism": "Fc glycan sialylation modulates anti-inflammatory activity.", "protein": "Monoclonal antibody (mAb)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Immunogenicity (adverse reactions)", "glycan_involvement": "Low NeuGc content is safer for human therapy.", "mechanism": "CHO cells produce low NeuGc, reducing immunogenic risk compared to other hosts.", "protein": "Monoclonal antibody (mAb)", "relationship_type": "protective", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Influenza A infection", "glycan_involvement": "Sialylation at Asn221 is critical for activity.", "mechanism": "Sialylated Fc inhibits viral hemagglutination.", "protein": "IgG1-Fc Asn221 mutant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Reduced efficacy of biopharmaceuticals", "glycan_involvement": "CHO-K1 produces more complex/sialylated N-glycans than CHO-S.", "mechanism": "Cell line-specific glycosylation (CHO-K1 vs CHO-S) affects N-glycan complexity and sialylation, impacting drug performance.", "protein": "Monoclonal antibody (mAb)", "relationship_type": "causal", "source_pmcid": "PMC12503014" }, { "confidence": "high", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Laminin is a heavily glycosylated ECM protein; its glycan chains are essential for matrix structure and cell signaling.", "mechanism": "Laminin 111 is a major component of the glycoprotein-rich luminal lining of VM structures and is sufficient in the ECM to allow VM formation.", "protein": "Laminin (especially Laminin 111)", "relationship_type": "causal", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Integrin \u03b21 is a glycoprotein; glycosylation affects its localization and function in VM.", "mechanism": "Integrin \u03b21 is required for all stages of VM formation by mediating cell-ECM signaling, especially with laminin 111.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Altered glycosylation may regulate integrin \u03b21 function in cancer.", "mechanism": "Integrin \u03b21 is essential for VM in ovarian cancer cell lines; its inhibition blocks VM.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Altered glycosylation may regulate integrin \u03b21 function in cancer.", "mechanism": "Integrin \u03b21 is essential for VM in breast cancer cell lines; its inhibition blocks VM.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12505716" }, { "confidence": "medium", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Laminin-5\u03b32 is a glycoprotein; glycosylation is important for its ECM interactions.", "mechanism": "Laminin-5\u03b32 is upregulated in VM and associated with VM structures in tumors.", "protein": "Laminin-5\u03b32", "relationship_type": "biomarker", "source_pmcid": "PMC12505716" }, { "confidence": "medium", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Nectin-4 is a glycoprotein; glycosylation may affect its cell adhesion properties.", "mechanism": "Nectin-4 is associated with VM formation and distant metastasis.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Integrin \u03b23 is a glycoprotein, but not functionally involved in VM here.", "mechanism": "Blocking integrin \u03b23 does not affect VM formation.", "protein": "Integrin \u03b23", "relationship_type": "not involved", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Collagen I is a glycoprotein; its glycosylation is not sufficient for VM.", "mechanism": "Collagen I alone in ECM does not support VM formation.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "not sufficient", "source_pmcid": "PMC12505716" }, { "confidence": "low", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Complex is glycosylated; glycosylation may affect ECM binding.", "mechanism": "Reported as a laminin receptor; possible involvement in VM signaling.", "protein": "Dystrophin glycoprotein complex", "relationship_type": "potential mediator", "source_pmcid": "PMC12505716" }, { "confidence": "low", "disease": "Vasculogenic mimicry (VM) in cancer", "glycan_involvement": "Glycosylation may affect its function.", "mechanism": "Reported as a laminin receptor; possible involvement in VM signaling.", "protein": "Lutheran blood group glycoprotein", "relationship_type": "potential mediator", "source_pmcid": "PMC12505716" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "EGFR is a glycoprotein; glycosylation may affect receptor function and drug response.", "mechanism": "EGFR targeted by tyrosine kinase inhibitors; failed to achieve durable success.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "HER2 is a glycoprotein; glycosylation may influence immune recognition and targeting.", "mechanism": "HER2 targeted by CAR-NK cells in clinical trials for refractory GB.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Infant-type Bihemispheric Glioma", "glycan_involvement": "ALK is a glycoprotein; glycosylation may modulate receptor activity.", "mechanism": "ALK fusion (ATIC-ALK) responded to ALK inhibitor lorlatinib.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "EV surface glycoproteins mediate cell-cell communication and immune modulation.", "mechanism": "EVs from GB cells remodel vasculature, suppress immune response, and serve as liquid biopsy biomarkers.", "protein": "Extracellular Vesicle Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Altered glycosylation patterns affect protein function and tumor behavior.", "mechanism": "Expression correlates with clinicopathological features and therapy response.", "protein": "Regulators of Glycosylation (e.g., glycosyltransferases)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation modulates cell adhesion and angiogenesis.", "mechanism": "Endothelial glycoproteins involved in tumor vasculature formation and microenvironment.", "protein": "Tumour Endothelial Cell Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Aberrant glycosylation may enhance EGFR signaling.", "mechanism": "EGFR signaling drives tumor growth and resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycoprotein composition affects EV uptake and targeting.", "mechanism": "EVs as vehicles for drug delivery and immunomodulation.", "protein": "Extracellular Vesicle Glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Modifying glycosylation alters drug sensitivity.", "mechanism": "Targeting glycosylation regulators may sensitize GB to drugs (Clorafabin, YM-155).", "protein": "Regulators of Glycosylation (e.g., glycosyltransferases)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12507580" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation status may affect HER2 detection and targeting.", "mechanism": "HER2 expression used to select patients for CAR-NK therapy.", "protein": "HER2", "relationship_type": "biomarker", "source_pmcid": "PMC12507580" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation at Asn153/154 and Asn67 (DENV-specific) modulates infectivity and immune response.", "mechanism": "E protein N-glycans mediate cell receptor recognition and are main targets for neutralizing antibodies and vaccine design.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Zika", "glycan_involvement": "N-glycosylation at Asn154 enhances lectin receptor affinity and virulence.", "mechanism": "Presence of N-glycosylation at Asn154 increases virulence and neuroinvasiveness in mice.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation at Asn130 and Asn207/208; glycan pattern affects lectin interactions and immune modulation.", "mechanism": "NS1 N-glycans are involved in folding, secretion, and pathogenesis; interaction with SRB1 receptor may influence disease.", "protein": "NS1 protein", "relationship_type": "causal", "source_pmcid": "PMC12509480" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "N-glycosylation at Asn69; impacts chaperone activity and viral particle stability.", "mechanism": "prM glycosylation is required for proper E protein folding and efficient secretion of viral particles.", "protein": "prM protein", "relationship_type": "causal", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "West Nile Virus (WNV)", "glycan_involvement": "N-glycosylation at E protein enhances pathogenicity.", "mechanism": "Addition of N-glycosylation site increases neuroinvasiveness and virulence.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "Afucosylation of IgG1 modulates immune response severity.", "mechanism": "Afucosylated IgG1 antibodies are associated with more severe dengue disease.", "protein": "IgG1 antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Antibody-dependent enhancement (ADE)", "glycan_involvement": "Modification/abolition of N-glycosylation reduces ADE risk.", "mechanism": "N-glycosylation of Fc region modulates ADE by affecting Fc receptor binding.", "protein": "Fc region of antibody", "relationship_type": "causal", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Zika", "glycan_involvement": "N-glycosylation at Asn130, Asn207/208; removal reduces infectious virus yield.", "mechanism": "Mutation or removal of NS1 N-glycosylation sites attenuates virus and enables vaccine development.", "protein": "NS1 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12509480" }, { "confidence": "medium", "disease": "Dengue/Zika", "glycan_involvement": "Artificial addition of N-glycosylation sites near non-favorable epitopes.", "mechanism": "Glycan masking redirects immune response to desired epitopes, improving vaccine specificity and reducing ADE.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "protective", "source_pmcid": "PMC12509480" }, { "confidence": "medium", "disease": "Japanese Encephalitis Virus (JEV)", "glycan_involvement": "E protein N-glycans interact with heparan sulfate; mimics block viral entry.", "mechanism": "HS-mimicking compounds block E protein-mediated cell attachment, inhibiting infection.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12509480" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Serum MOG-IgG antibodies are used as a diagnostic biomarker for MOGAD; high-titer positivity is required for diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12509963" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG may influence antibody binding and specificity.", "mechanism": "MOG-IgG antibodies are rarely present in MS; their presence may lead to misdiagnosis if not interpreted with clinical/MRI context.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC12509963" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may modulate immune recognition.", "mechanism": "AQP4-IgG antibodies are a diagnostic biomarker for NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12509963" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation status may affect antigenicity.", "mechanism": "MOG-IgG is negative in AQP4-IgG-positive NMOSD, helping distinguish MOGAD from NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC12509963" }, { "confidence": "medium", "disease": "Clinically isolated syndrome (CIS)", "glycan_involvement": "Glycosylation may influence antibody detection.", "mechanism": "MOG-IgG may rarely be detected in CIS; careful interpretation is required to avoid misdiagnosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC12509963" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation reduces CBG stability and binding capacity.", "mechanism": "PMM2-CDG causes hypoglycosylation of CBG, leading to decreased CBG levels and altered cortisol binding.", "protein": "CBG", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "Central Adrenal Insufficiency", "glycan_involvement": "N-glycosylation required for CBG function; hypoglycosylation lowers measured total cortisol.", "mechanism": "Low CBG due to hypoglycosylation leads to low total plasma cortisol, mimicking adrenal insufficiency biochemically.", "protein": "CBG", "relationship_type": "biomarker", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "N-glycosylation affects TBG stability and T4-binding activity.", "mechanism": "Low TBG due to hypoglycosylation results in low total T4, mimicking hypothyroidism biochemically.", "protein": "TBG", "relationship_type": "biomarker", "source_pmcid": "PMC12511663" }, { "confidence": "medium", "disease": "Hypergonadotropic Hypogonadism", "glycan_involvement": "N-glycosylation modulates FSH secretion, metabolism, and potency.", "mechanism": "Altered glycosylation of FSH may affect its clearance and biopotency, contributing to gonadal axis dysfunction.", "protein": "FSH", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "N-glycosylation pattern altered in PMM2-CDG.", "mechanism": "Hypoglycosylated transferrin is diagnostic for PMM2-CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "Central Adrenal Insufficiency", "glycan_involvement": "N-glycosylation critical for CBG function; loss of Asn238 site reduces binding.", "mechanism": "SERPINA6 mutations or hypoglycosylation cause low CBG and low total cortisol, but normal free cortisol.", "protein": "SERPINA6 (CBG gene product)", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "N-glycosylation affects TBG half-life and immunoreactivity.", "mechanism": "SERPINA7 mutations or hypoglycosylation cause low TBG and low total T4, but normal free T4.", "protein": "SERPINA7 (TBG gene product)", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "N-glycosylation influences hormone stability and receptor interaction.", "mechanism": "PMM2-CDG may affect N-glycosylated hormones like GH, potentially impacting endocrine axes.", "protein": "GH", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "N-glycosylation influences hormone stability and receptor interaction.", "mechanism": "PMM2-CDG may affect N-glycosylated hormones like LH, potentially impacting endocrine axes.", "protein": "LH", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "medium", "disease": "Fatigue and hypotension (SERPINA6 variants)", "glycan_involvement": "N-glycosylation affects CBG function and hormone binding.", "mechanism": "SERPINA6 mutations or hypoglycosylation may cause symptoms not directly attributed to adrenal insufficiency.", "protein": "CBG", "relationship_type": "causal", "source_pmcid": "PMC12511663" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "FN1 is heavily glycosylated; glycosylation modulates ECM interactions and fibrosis.", "mechanism": "Upregulated FN1 promotes renal fibrosis via TGF-\u03b2 pathway and ECM deposition.", "protein": "FN1 (Fibronectin 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "ICAM1 N-glycosylation regulates cell adhesion and immune cell recruitment.", "mechanism": "Upregulated ICAM1 drives leukocyte adhesion and inflammation, sustaining kidney injury.", "protein": "ICAM1 (Intercellular Adhesion Molecule 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "ANXA2 glycosylation may affect membrane localization and interaction with ECM.", "mechanism": "Upregulated ANXA2 promotes fibrosis, inflammation, and cell proliferation in kidney.", "protein": "ANXA2 (Annexin A2)", "protein_enriched": { "function": "Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress respons", "gene_name": "ANXA2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P07355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "APOA1 glycosylation influences lipid binding and anti-inflammatory function.", "mechanism": "Downregulated APOA1 impairs HDL biogenesis, cholesterol efflux, and antioxidative protection.", "protein": "APOA1 (Apolipoprotein A-I)", "relationship_type": "protective", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Renal Fibrosis", "glycan_involvement": "Glycosylation of FN1 is essential for ECM assembly and fibrotic signaling.", "mechanism": "FN1 overexpression directly drives ECM accumulation and fibrotic remodeling.", "protein": "FN1 (Fibronectin 1)", "relationship_type": "causal", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Renal Fibrosis", "glycan_involvement": "N-glycans on ICAM1 modulate immune cell binding and fibrotic response.", "mechanism": "ICAM1-mediated inflammation perpetuates fibrosis through immune cell infiltration.", "protein": "ICAM1 (Intercellular Adhesion Molecule 1)", "relationship_type": "causal", "source_pmcid": "PMC12513384" }, { "confidence": "medium", "disease": "Chronic Glomerulopathies", "glycan_involvement": "Glycosylation may affect ANXA2 stability and biomarker utility.", "mechanism": "Elevated ANXA2 predicts poor prognosis and correlates with inflammation and fibrosis.", "protein": "ANXA2 (Annexin A2)", "protein_enriched": { "function": "Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress respons", "gene_name": "ANXA2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P07355" }, "relationship_type": "biomarker", "source_pmcid": "PMC12513384" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma", "glycan_involvement": "Glycosylation may regulate ANXA2 cell surface expression in cancer.", "mechanism": "ANXA2 overexpression is associated with tumor progression and poor outcome.", "protein": "ANXA2 (Annexin A2)", "protein_enriched": { "function": "Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress respons", "gene_name": "ANXA2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P07355" }, "relationship_type": "biomarker", "source_pmcid": "PMC12513384" }, { "confidence": "low", "disease": "Nephrolithiasis", "glycan_involvement": "Glycosylation may modulate ANXA2's role in calcium binding.", "mechanism": "ANXA2 participates in calcium-dependent pathways linked to kidney stone formation.", "protein": "ANXA2 (Annexin A2)", "protein_enriched": { "function": "Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress respons", "gene_name": "ANXA2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P07355" }, "relationship_type": "causal", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation affects APOA1's stability and biomarker reliability.", "mechanism": "APOA1 levels positively correlate with eGFR, indicating renal function.", "protein": "APOA1 (Apolipoprotein A-I)", "relationship_type": "biomarker", "source_pmcid": "PMC12513384" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies target MOG on oligodendrocyte/myelin surfaces, triggering CNS inflammation and demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition.", "mechanism": "MOG antibodies induce demyelination, leading to ADEM phenotype in children.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "medium", "disease": "Cerebral cortical encephalitis", "glycan_involvement": "Glycosylation may influence epitope exposure.", "mechanism": "MOG antibodies can cause isolated cortical inflammation and encephalitis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Potential role in immune complex formation; not directly studied.", "mechanism": "MOG antibodies associated with leptomeningeal inflammation without parenchymal lesions.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "medium", "disease": "Tumefactive demyelinating lesion", "glycan_involvement": "Glycosylation may affect immune response severity.", "mechanism": "MOG antibodies can cause large, solitary demyelinating lesions mimicking tumors.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "medium", "disease": "Cerebellitis/brainstem encephalitis", "glycan_involvement": "Not specified; presumed similar to other CNS regions.", "mechanism": "MOG antibodies induce demyelination in cerebellum/brainstem.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "low", "disease": "Leukodystrophy-like syndrome", "glycan_involvement": "Not specified.", "mechanism": "MOG antibodies can rarely cause symmetric, confluent white matter lesions mimicking leukodystrophy.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "low", "disease": "Multiple sclerosis-like syndrome", "glycan_involvement": "Not specified.", "mechanism": "MOG antibodies can rarely produce MS-like white matter lesions.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12513890" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation may affect antibody detection and assay performance.", "mechanism": "Serum MOG-IgG is a diagnostic biomarker for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12513890" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation may influence therapeutic antibody binding.", "mechanism": "Targeting MOG-specific immune responses (e.g., with immunosuppression) is effective in MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12513890" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Formation of advanced glycation end products (AGEs) on elastin fibers.", "mechanism": "Elastin in eccrine coils undergoes abnormal glycosylation and degradation, leading to elastosis detectable in skin biopsies.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "high", "disease": "Prediabetes", "glycan_involvement": "AGE formation on elastin fibers precedes overt diabetes.", "mechanism": "Early elastin glycosylation and elastosis in eccrine coils is associated with prediabetic states.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycation accelerates elastin degradation.", "mechanism": "Elastin degradation releases elastokines, which promote atherosclerosis.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC12515537" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "AGE-modified elastin increases peptide release.", "mechanism": "Elastin-derived peptides (elastokines) from degraded/glycated elastin contribute to insulin resistance.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC12515537" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Lysozyme binds to glycosylated (AGE-modified) elastin.", "mechanism": "Lysozyme immunoreactivity in elastic fibers indicates abnormal glycosylation in diabetic skin.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "high", "disease": "Prediabetes", "glycan_involvement": "Lysozyme detects AGEs on elastin.", "mechanism": "Lysozyme immunostaining confirms early glycosylation of elastin in prediabetic patients.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "medium", "disease": "Cardiovascular Complications", "glycan_involvement": "AGE-modified elastin is more prevalent in affected patients.", "mechanism": "ECE (eccrine coil elastosis) correlates with cardiovascular complications in metabolic disease.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "medium", "disease": "Dermal Solar Elastosis", "glycan_involvement": "Glycation and UV damage synergistically modify elastin.", "mechanism": "AGE formation on elastin is intensified by sun exposure, leading to dermal elastosis.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "medium", "disease": "Microangiopathy", "glycan_involvement": "AGEs alter elastin structure and function in vessel walls.", "mechanism": "Glycated elastin contributes to vascular changes seen in diabetic microangiopathy.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC12515537" }, { "confidence": "low", "disease": "Necrobiosis Lipoidica", "glycan_involvement": "AGE-modified elastin is a feature in affected skin.", "mechanism": "Histological changes in elastin (glycosylation, fragmentation) are observed in necrobiosis lipoidica associated with diabetes.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "biomarker", "source_pmcid": "PMC12515537" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Promotes insulin resistance via TLR4/NF-\u03baB pathway activation.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation affects stability and function.", "mechanism": "Promotes vascular inflammation and arterial calcification via TLR4/NF-\u03baB.", "protein": "Fetuin-A", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12515645" }, { "confidence": "medium", "disease": "Cancer (HCC, others)", "glycan_involvement": "Glycosylation modulates tumor-promoting activity.", "mechanism": "Activates PI3K/Akt and MAPK pathways, promoting tumor progression.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Excess SeP impairs insulin signaling, increases risk.", "protein": "Selenoprotein P", "protein_enriched": { "function": "Might be responsible for some of the extracellular antioxidant defense properties of selenium or might be involved in the transport of selenium. May supply selenium to tissues such as brain and testis", "gene_name": "SELENOP", "glycan_count": 53, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G22310AV", "G56518TU", "G70232NH", "G70888PK", "G83633GK", "G94470IW", "G04657PL", "G06356OH", "G10486CT", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G35541EV", "G40574BA", "G40834TG", "G41071NU", "G45395BF", "G45504EY", "G46691LC", "G47644PP", "G48414YA", "G57776ZS", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G83646BJ", "G87661QW", "G90659AW", "G93718GY", "G95865ZB", "G17015OC", "G29068FM", "G43417UB", "G11911BT", "G25418HZ", "G42124LM", "G45495MK", "G47518TP", "G52527GH", "G84452RH", "G49108TO" ], "uniprot_id": "P49908" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "NAFLD/NASH", "glycan_involvement": "GlycoPEGylation enhances therapeutic analog stability.", "mechanism": "Improves insulin sensitivity, reduces hepatic steatosis and inflammation.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation impacts secretion and receptor binding.", "mechanism": "Vasculoprotective, but elevated in metabolic dysfunction (reflects resistance).", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "Cancer (breast, prostate, colon, HCC)", "glycan_involvement": "Glycosylation affects receptor interaction and stability.", "mechanism": "Promotes cell proliferation, migration, invasion via IGF-1R/PI3K/AKT/STAT3.", "protein": "IGF-1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Inhibits LPL, raising triglycerides and cholesterol; inhibition lowers lipids.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12515645" }, { "confidence": "medium", "disease": "NAFLD/NASH", "glycan_involvement": "Glycosylation modulates secretion and inflammatory activity.", "mechanism": "Promotes hepatic inflammation and insulin resistance.", "protein": "ANGPTL4", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697", "gene_name": "ANGPTL4", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G14994KB", "G22310AV", "G23863VK", "G27058EU", "G31852PQ", "G37412TK", "G37881RL", "G41071NU", "G45395BF", "G45495MK", "G48414YA", "G52527GH", "G56784JY", "G57818FI", "G62461SM", "G62765YT", "G71146HJ", "G75983OB", "G80920RR", "G84452RH", "G90659AW", "G43417UB", "G53434XO", "G88713AC" ], "uniprot_id": "Q9BY76" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "Fibrosis/Tissue Repair", "glycan_involvement": "Glycosylation required for activation and receptor binding.", "mechanism": "Promotes tissue regeneration, inhibits fibrosis via c-MET signaling.", "protein": "HGF", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01543ZX", "G11629QQ", "G17689DH", "G22310AV", "G48414YA", "G52126RR", "G52527GH", "G57789QC", "G60542VK", "G64394MX", "G74239ZQ", "G77252PU", "G89664KV", "G93656SY", "G45637XA", "G81006GJ", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G40834TG", "G41071NU", "G42124LM", "G45395BF", "G86880BF", "G90659AW", "G41247ZX", "G46691LC", "G62765YT", "G80920RR", "G83460ZZ" ], "uniprot_id": "P14210" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12515645" }, { "confidence": "high", "disease": "GM2 gangliosidosis", "glycan_involvement": "Impaired degradation of sialylated glycan on GM2.", "mechanism": "Deficiency of \u03b2-hexosaminidase leads to GM2 accumulation in lysosomes.", "protein": "GM2", "relationship_type": "causal", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Cholera toxin-mediated disease", "glycan_involvement": "GM1 glycan acts as cellular receptor for toxin.", "mechanism": "Cholera toxin binds GM1 on host cells to mediate toxin entry.", "protein": "GM1", "relationship_type": "causal", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Sialylated glycans on gangliosides serve as co-receptors.", "mechanism": "SARS-CoV-2 spike protein binds gangliosides to enhance cell entry.", "protein": "GM1, GM2, GM3", "relationship_type": "facilitative", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Sialylated glycan structure critical for EGFR interaction.", "mechanism": "GM3 overexpressed in tumors; modulates EGFR signaling and immune evasion.", "protein": "GM3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Disialylated glycan epitope recognized by therapeutics.", "mechanism": "GD2 is highly expressed on neuroblastoma cells; targeted by mAbs and CAR-T.", "protein": "GD2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Shiga toxin-mediated disease", "glycan_involvement": "Gb3 glycan is the cellular receptor for toxin.", "mechanism": "Shiga toxin binds Gb3 on host cells to mediate cytotoxicity.", "protein": "Gb3", "relationship_type": "causal", "source_pmcid": "PMC12515973" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "GalCer glycan acts as fusion receptor.", "mechanism": "HIV gp120 binds GalCer to facilitate viral entry.", "protein": "GalCer", "relationship_type": "facilitative", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Small cell lung cancer", "glycan_involvement": "Fucosylated glycan epitope is target for antibody binding.", "mechanism": "FucGM1 is overexpressed in SCLC and targeted by therapeutic antibodies.", "protein": "FucGM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Sialylated glycans interact with immune cell receptors (e.g., Siglecs).", "mechanism": "Shedding of gangliosides from tumors suppresses T cell and DC function.", "protein": "GM2, GM3, GD3", "relationship_type": "immunosuppressive", "source_pmcid": "PMC12515973" }, { "confidence": "medium", "disease": "Bacterial infection (e.g., E. coli, C. albicans)", "glycan_involvement": "LacCer glycan serves as binding site for microbes.", "mechanism": "LacCer on epithelial cells mediates adhesion of pathogens.", "protein": "LacCer", "relationship_type": "facilitative", "source_pmcid": "PMC12515973" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation of multiple proteins.", "mechanism": "Loss of PMM2 activity impairs mannose-1-phosphate production, disrupting N-glycosylation.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Hypoglycosylated transferrin detected by isoelectric focusing.", "mechanism": "Altered glycoforms of transferrin indicate defective N-glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Coagulation disorders (bleeding/thrombosis)", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Reduced glycosylation leads to decreased antithrombin III activity, increasing bleeding/thrombosis risk.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Coagulation disorders (bleeding/thrombosis)", "glycan_involvement": "N-glycosylation affects secretion and function.", "mechanism": "Impaired glycosylation reduces factor XI activity, contributing to coagulopathy.", "protein": "Factor XI", "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation defects in liver proteins.", "mechanism": "Defective glycosylation of hepatic proteins leads to elevated transaminases and liver dysfunction.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Global developmental delay/intellectual impairment", "glycan_involvement": "N-glycosylation critical for neuronal protein function.", "mechanism": "Impaired glycosylation affects CNS development and function.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "N-glycosylation required for antithrombin III function.", "mechanism": "Low antithrombin III activity reflects glycosylation defects in PMM2-CDG.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "N-glycosylation required for factor XI secretion and function.", "mechanism": "Low factor XI activity is a marker of glycosylation defects in PMM2-CDG.", "protein": "Factor XI", "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation of transferrin is liver-dependent.", "mechanism": "Altered transferrin glycoforms reflect hepatic glycosylation status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Coagulation disorders (bleeding/thrombosis)", "glycan_involvement": "N-glycosylation of coagulation glycoproteins impaired.", "mechanism": "PMM2 deficiency leads to hypoglycosylation of coagulation factors, causing bleeding/thrombosis.", "protein": "Phosphomannomutase-2 (PMM2)", "protein_enriched": { "function": "Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions", "gene_name": "PMM2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G49108TO" ], "uniprot_id": "O15305" }, "relationship_type": "causal", "source_pmcid": "PMC12516010" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "LRG-1 levels are elevated in KD serum and associated with IL-1\u03b2 signaling and inflammation.", "protein": "Leucin-rich \u03b1-2-glycoprotein 1 (LRG-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Endothelial-to-mesenchymal transition (EndMT)", "glycan_involvement": "N-glycosylation may affect receptor interactions.", "mechanism": "LRG-1 is upregulated during EndMT and modulates TGF\u03b2 signaling, but is not a direct driver in KD context.", "protein": "Leucin-rich \u03b1-2-glycoprotein 1 (LRG-1)", "relationship_type": "marker/modulator", "source_pmcid": "PMC12516014" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation essential for ligand binding.", "mechanism": "Upregulated in KD serum, indicating endothelial activation.", "protein": "E-selectin (SELE)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated in KD, associated with EndMT and inflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation affects stability.", "mechanism": "Upregulated in KD serum, linked to EndMT and vascular remodeling.", "protein": "Growth differentiation factor 15 (GDF-15)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Elevated in KD, associated with fibrosis.", "protein": "Soluble interleukin 1 receptor-like 1 (ST2)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation modulates cell-cell interactions.", "mechanism": "Upregulated in KD and EndMT, mediates leukocyte adhesion and transition.", "protein": "Intercellular adhesion molecule 1 (ICAM1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12516014" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "Upregulated in KD and EndMT, promotes leukocyte adhesion.", "protein": "Vascular cell adhesion molecule 1 (VCAM1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Endothelial-to-mesenchymal transition (EndMT)", "glycan_involvement": "Glycosylation modulates hyaluronan binding.", "mechanism": "Upregulated during EndMT in KD context.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "marker", "source_pmcid": "PMC12516014" }, { "confidence": "medium", "disease": "Coronary artery aneurysm", "glycan_involvement": "N-glycosylation required for circulating levels.", "mechanism": "LRG-1 levels are higher in KD patients with CAA.", "protein": "Leucin-rich \u03b1-2-glycoprotein 1 (LRG-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12516014" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Altered N-glycosylation and reduced fucosylation at specific sites in UC.", "mechanism": "Decreased expression in UC tissue and serum; involved in endopeptidase activity and mucosal barrier integrity.", "protein": "CLCA1", "protein_enriched": { "function": "Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium ions concentration is low and inhibits guanylyl cyclases when free calcium ions concentration is elevated. This Ca(2+)-sensitive regulatio", "gene_name": "GUCA1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95843" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Increased fucosylation and altered N-glycan profiles in UC tissue.", "mechanism": "Increased serum levels in UC; involved in extracellular matrix and coagulation cascades.", "protein": "FGB", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in", "gene_name": "FGB", "glycan_count": 124, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G81399MY", "G00912UN", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G09197ZW", "G10486CT", "G10846ZT", "G11314AS", "G11911BT", "G12745LE", "G13131HA", "G14994KB", "G15038BD", "G15664MX", "G18647XP", "G20706XG", "G22572EH", "G22768VO", "G23505EP", "G23863VK", "G25079LO", "G25418HZ", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G31916IQ", "G31986NC", "G34989PA", "G35029YA", "G35253PZ", "G36191CD", "G37399XV", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G49018RC", "G49642SA", "G49955PK", "G50045TK", "G50073PQ", "G50282JC", "G54010QB", "G54600FO", "G55383ZG", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G70441OD", "G70619PT", "G71146HJ", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G75850OP", "G75983OB", "G77547TA", "G80920RR", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G87051GH", "G87389XI", "G89098OM", "G90659AW", "G91365ZQ", "G92050GC", "G92551JA", "G94470IW", "G95865ZB", "G17015OC", "G49108TO" ], "uniprot_id": "P02675" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Site-specific N-glycosylation changes at multiple sites in UC.", "mechanism": "Elevated expression in UC tissue; associated with ECM remodeling.", "protein": "FBN1", "protein_enriched": { "function": "Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:15062093, Pub", "gene_name": "FBN1", "glycan_count": 111, "glycosylation_sites_count": 42, "glytoucan_ids": [ "G71142DF", "G00406II", "G02815KT", "G05724UK", "G06110VR", "G10486CT", "G12313PD", "G14260UH", "G22310AV", "G23719VF", "G25637MV", "G28541PG", "G31852PQ", "G33609NS", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G46902YN", "G50045TK", "G57776ZU", "G62765YT", "G64527OM", "G70101JE", "G72735IY", "G80920RR", "G82463GQ", "G84820NF", "G86500WE", "G89827JR", "G92050GC", "G20706XG", "G23863VK", "G25418HZ", "G37509XX", "G66621EA", "G77669RF", "G80223IX", "G84452RH", "G91636VS", "G02030ZB", "G02528FI", "G02886BB", "G04657PL", "G04672QB", "G20425TQ", "G25451PN", "G27058EU", "G27126ED", "G29880MM", "G30769VJ", "G39619TI", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G51640FO", "G59536GA", "G60033FS", "G60177UT", "G63381RX", "G65807AE", "G66766XF", "G70375MX", "G72398FA", "G87051GH", "G89098OM", "G90093AU", "G90659AW", "G93683YO", "G95046LV", "G02315DX", "G11911BT", "G26436YP", "G45504EY", "G70418MS", "G70822IO", "G77547TA", "G31916IQ", "G40319VM", "G62461SM", "G09197ZW", "G19379ID", "G42124LM", "G46687AB", "G82830MN", "G72797UR", "G79568CQ", "G96577RX", "G43417UB", "G28681TP", "G12270AG", "G11629QQ", "G12793SR", "G13694XX", "G34989PA", "G51413EV", "G52527GH", "G83460ZZ", "G87123QX", "G92135MA", "G93656SY", "G98611JV", "G08918WF", "G23010ZW", "G43223CG", "G90382BL", "G49108TO", "G56784JY", "G75983OB", "G14796IU" ], "uniprot_id": "P35555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Altered N-glycosylation may help differentiate UC from CD.", "mechanism": "Decreased serum levels in CD, similar to UC.", "protein": "CLCA1", "protein_enriched": { "function": "Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium ions concentration is low and inhibits guanylyl cyclases when free calcium ions concentration is elevated. This Ca(2+)-sensitive regulatio", "gene_name": "GUCA1C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95843" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Altered N-glycosylation; may help distinguish IBD from healthy controls.", "mechanism": "Increased serum levels in CD, similar to UC.", "protein": "FGB", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in", "gene_name": "FGB", "glycan_count": 124, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G81399MY", "G00912UN", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G09197ZW", "G10486CT", "G10846ZT", "G11314AS", "G11911BT", "G12745LE", "G13131HA", "G14994KB", "G15038BD", "G15664MX", "G18647XP", "G20706XG", "G22572EH", "G22768VO", "G23505EP", "G23863VK", "G25079LO", "G25418HZ", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G31916IQ", "G31986NC", "G34989PA", "G35029YA", "G35253PZ", "G36191CD", "G37399XV", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G49018RC", "G49642SA", "G49955PK", "G50045TK", "G50073PQ", "G50282JC", "G54010QB", "G54600FO", "G55383ZG", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G70441OD", "G70619PT", "G71146HJ", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G75850OP", "G75983OB", "G77547TA", "G80920RR", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G87051GH", "G87389XI", "G89098OM", "G90659AW", "G91365ZQ", "G92050GC", "G92551JA", "G94470IW", "G95865ZB", "G17015OC", "G49108TO" ], "uniprot_id": "P02675" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Loss of complex N-glycans; truncated O-glycans (from literature).", "mechanism": "Decreased N-glycosylation and protein levels compromise mucus barrier, promoting inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Site-specific N-glycosylation increase at N327.", "mechanism": "Elevated glycoform (H5N3) in UC; involved in protease activity and inflammation.", "protein": "CTSA", "protein_enriched": { "function": "Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stabilit", "gene_name": "CTSA", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G02886BB", "G04854VP", "G05049YU", "G05724UK", "G06110VR", "G07755XJ", "G14669DU", "G17689EW", "G23719VF", "G25451PN", "G27126ED", "G28541PG", "G28681TP", "G31852PQ", "G35029YA", "G39188ZX", "G41247ZX", "G46503DX", "G47644PP", "G47950XN", "G49018RC", "G62765YT", "G63041LO", "G70619PT", "G72747WU", "G77547TA", "G80920RR", "G83460ZZ", "G83633GK", "G85269DF", "G90659AW", "G92050GC", "G92135MA", "G99668VU", "G00912UN", "G01650EU", "G08290VR", "G08918WF", "G10486CT", "G10846ZT", "G23294PN", "G37399XV", "G39446WN", "G40574BA", "G42124LM", "G45504EY", "G49955PK", "G57317CE", "G57776ZU", "G59626AS", "G65184UU", "G72787SB", "G72790NZ", "G73968GN", "G95865ZB", "G49108TO" ], "uniprot_id": "P10619" }, "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Reduced S2H5N4 glycan at N454 in UC.", "mechanism": "Decreased glycoform abundance in UC; may reflect oxidative stress.", "protein": "HPX", "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Increased S1H5N4F1 glycan at N127 in UC.", "mechanism": "Elevated glycoform in UC; involved in ECM structure.", "protein": "LUM", "relationship_type": "biomarker", "source_pmcid": "PMC12516497" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Distinct N-glycans (H8N2, H9N2) at single glycosite.", "mechanism": "Altered glycosylation machinery affects N-glycosylation of multiple proteins in UC.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC12516497" }, { "confidence": "high", "disease": "Drug resistance", "glycan_involvement": "Glycosylation required for P-gp function and trafficking.", "mechanism": "P-gp limits berberine absorption; inhibition increases bioavailability.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation essential for LDLR folding and function.", "mechanism": "Berberine upregulates LDLR, enhancing LDL clearance and reducing atherosclerosis risk.", "protein": "LDL receptor (LDLR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "PCSK9 glycosylation affects secretion and LDLR interaction.", "mechanism": "Berberine inhibits PCSK9, preventing LDLR degradation and lowering LDL cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "GLP-1 is O-glycosylated, affecting stability.", "mechanism": "Berberine increases GLP-1 levels, improving insulin secretion and glycemic control.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "high", "disease": "Kernicterus", "glycan_involvement": "Albumin glycosylation modulates ligand binding.", "mechanism": "Berberine displaces bilirubin from albumin, increasing unbound bilirubin and risk of kernicterus.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for TLR4 cell surface expression.", "mechanism": "Berberine reduces TLR4-mediated inflammation, protecting against atherosclerosis.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation required for MTTP function.", "mechanism": "Berberine normalizes MTTP expression, improving lipoprotein metabolism and reducing hepatic steatosis.", "protein": "MTTP", "protein_enriched": { "function": "Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:15897609, PubMed:16478722, PubMed:22236406, PubMed:23475612, PubMed:25108285, PubMed:", "gene_name": "MTTP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55157" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Glycosylation affects CYP3A4 stability.", "mechanism": "Berberine inhibits CYP3A4, affecting drug metabolism and increasing drug levels.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Immunosuppression", "glycan_involvement": "N-glycosylation required for CD19 surface expression.", "mechanism": "Berberine reduces CD19+ B-cell counts, leading to immunosuppression.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "causal", "source_pmcid": "PMC12516553" }, { "confidence": "medium", "disease": "Immunosuppression", "glycan_involvement": "N-glycosylation required for CD4 function.", "mechanism": "Berberine reduces CD4+ T-cell counts, contributing to immunosuppression.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12516553" }, { "confidence": "high", "disease": "ALG3-CDG", "glycan_involvement": "Impaired addition of the 6th mannose residue leads to truncated N-glycans (e.g., Hex3HexNAc2, Hex4HexNAc2) on glycoproteins.", "mechanism": "Pathogenic variants in ALG3 gene cause deficient alpha-1,3-mannosyltransferase activity, disrupting N-glycan precursor synthesis in the ER.", "protein": "Alpha-1,3-mannosyltransferase (ALG3)", "protein_enriched": { "function": "Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-g", "gene_name": "ALG3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92685" }, "relationship_type": "causal", "source_pmcid": "PMC12517101" }, { "confidence": "high", "disease": "CDG type I", "glycan_involvement": "Incomplete N-glycosylation of transferrin is detected by isoelectric focusing.", "mechanism": "Altered glycoforms (increased asialo- and disialo-transferrin, decreased tetrasialo-transferrin) indicate N-glycosylation defects.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "high", "disease": "ALG3-CDG", "glycan_involvement": "Defective N-glycosylation due to ALG3 deficiency.", "mechanism": "Abnormal N-glycan profile with increased truncated oligomannose structures (Hex3HexNAc2, Hex4HexNAc2) and decreased higher-order mannose structures.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "ALG3-CDG", "glycan_involvement": "Altered N-glycosylation/fucosylation patterns.", "mechanism": "Reduced overall fucosylation in serum N-glycans may reflect decreased IgG levels, as seen in some CDG subtypes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation due to PMM2 deficiency.", "mechanism": "Similar N-glycan profile changes (increased Hex3HexNAc2, Hex4HexNAc2) as in ALG3-CDG, but distinguished by presence of tetrasaccharide biomarker.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "MPI-CDG", "glycan_involvement": "Defective N-glycosylation due to MPI deficiency.", "mechanism": "Similar N-glycan profile changes as in ALG3-CDG, but distinguished by specific glycobiomarkers.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "ALG1-CDG", "glycan_involvement": "Defective N-glycosylation due to ALG1 deficiency.", "mechanism": "Abnormal N-glycan profile with unique pentasaccharide (Neu5Ac1Gal1Fuc1GlcNAc2) distinguishes ALG1-CDG from ALG3-CDG.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "ALG11-CDG", "glycan_involvement": "Defective N-glycosylation due to ALG11 deficiency.", "mechanism": "Increased Hex3HexNAc2-PP-dolichol and Hex4HexNAc2-PP-dolichol in fibroblasts; similar but distinct from ALG3-CDG.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "ALG12-CDG", "glycan_involvement": "Defective N-glycosylation due to ALG12 deficiency.", "mechanism": "Increased Hex5HexNAc2 and Hex6HexNAc2 distinguish ALG12-CDG from ALG3-CDG.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "medium", "disease": "ALG9-CDG", "glycan_involvement": "Defective N-glycosylation due to ALG9 deficiency.", "mechanism": "Increased Hex4HexNAc2-Hex6HexNAc2 and reduced Hex7HexNAc2-Hex9HexNAc2; Hex3HexNAc2 not detected, differentiating from ALG3-CDG.", "protein": "General serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12517101" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is glycosylated; glycosylation may affect membrane localization and stability.", "mechanism": "Mutations in dystrophin gene cause loss of dystrophin protein, leading to muscle membrane instability and progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "AST is glycosylated, which may affect its stability and secretion.", "mechanism": "Elevated AST in plasma reflects muscle membrane damage and leakage of intracellular enzymes.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "ALT is glycosylated, which may affect its stability and secretion.", "mechanism": "Elevated ALT in plasma reflects muscle membrane damage and leakage of intracellular enzymes.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "CK is glycosylated, which may affect its serum half-life.", "mechanism": "CK is released into plasma due to muscle membrane damage; highly elevated in DMD.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Aldolase is glycosylated, which may affect its stability.", "mechanism": "Elevated aldolase in plasma reflects muscle breakdown.", "protein": "Aldolase", "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "medium", "disease": "Muscle membrane damage", "glycan_involvement": "Glycosylation may modulate dystrophin's interaction with membrane proteins.", "mechanism": "Absence of dystrophin leads to increased sarcolemmal permeability and muscle fiber degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12517537" }, { "confidence": "medium", "disease": "Failure to thrive", "glycan_involvement": "Glycosylation may affect dystrophin's function in muscle development.", "mechanism": "Early muscle weakness and poor feeding due to dystrophin deficiency can contribute to failure to thrive.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Transaminitis", "glycan_involvement": "Glycosylation may affect AST's release and detection.", "mechanism": "Elevated AST is a marker of transaminitis, which in this context is due to muscle rather than liver injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Transaminitis", "glycan_involvement": "Glycosylation may affect ALT's release and detection.", "mechanism": "Elevated ALT is a marker of transaminitis, which in this context is due to muscle rather than liver injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Muscle membrane damage", "glycan_involvement": "Glycosylation may affect CK's serum stability.", "mechanism": "CK elevation reflects muscle membrane damage and increased permeability.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12517537" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "AGER is a glycoprotein receptor for advanced glycation end products; glycosylation affects ligand binding and immune signaling.", "mechanism": "Soluble RAGE (sRAGE) is protective against liver inflammation; absence of RAGE worsens AIH in mice.", "protein": "AGER", "relationship_type": "causal/protective", "source_pmcid": "PMC12517900" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "BTN2A1 is a glycoprotein; glycosylation may modulate T cell receptor interactions.", "mechanism": "BTN2A1 activates V\u03b39V\u03b42T cells, promoting Th1 cytokine secretion and immune imbalance, increasing AIH risk.", "protein": "BTN2A1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12517900" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "BTN3A2 is a glycoprotein; glycosylation may affect immune checkpoint function.", "mechanism": "BTN3A2 inhibits T cell proliferation and cytokine production, maintaining immune tolerance and reducing AIH risk.", "protein": "BTN3A2", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12517900" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "HLA-E is a glycoprotein; N-glycosylation is essential for antigen presentation and stability.", "mechanism": "High HLA-E expression inhibits NK cell clearance of pathogenic T cells, increasing AIH risk.", "protein": "HLA-E", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates receptor function and immune signaling.", "mechanism": "sRAGE is protective in SLE by reducing inflammation.", "protein": "AGER", "relationship_type": "protective", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Hashimoto\u2019s thyroiditis", "glycan_involvement": "Glycosylation affects ligand binding.", "mechanism": "sRAGE reduces autoimmune thyroid inflammation.", "protein": "AGER", "relationship_type": "protective", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 syndrome", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "sRAGE protects against autoimmune nerve damage.", "protein": "AGER", "relationship_type": "protective", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Primary sclerosing cholangitis", "glycan_involvement": "Glycosylation may affect immune checkpoint activity.", "mechanism": "BTN3A2 expression is protective by maintaining immune tolerance.", "protein": "BTN3A2", "relationship_type": "protective", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Behcet\u2019s disease", "glycan_involvement": "N-glycosylation required for antigen presentation.", "mechanism": "HLA-E*01:03 allele increases risk by inhibiting NK cell activity.", "protein": "HLA-E", "relationship_type": "causal", "source_pmcid": "PMC12517900" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus", "glycan_involvement": "N-glycosylation affects peptide binding and immune regulation.", "mechanism": "HLA-E01:01/01:03 heterozygosity linked to severe, early-onset T1DM.", "protein": "HLA-E", "relationship_type": "causal", "source_pmcid": "PMC12517900" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b1-dystroglycan is heavily glycosylated; glycosylation is essential for laminin binding and muscle integrity.", "mechanism": "Loss of dystrophin disrupts DAPC, leading to downregulation of dystroglycans and sarcolemmal instability.", "protein": "Dystroglycan (\u03b1 and \u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "Other muscular dystrophies", "glycan_involvement": "Sarcoglycans are glycoproteins; glycosylation is important for complex stability.", "mechanism": "Genetic loss of sarcoglycans causes distinct muscular dystrophies.", "protein": "Sarcoglycan complex", "relationship_type": "causal", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation of \u03b1-dystroglycan remains critical for function.", "mechanism": "Internally deleted dystrophin partially preserves DAPC and dystroglycan function.", "protein": "Dystroglycan (\u03b1 and \u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12518133" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy", "glycan_involvement": "Capsid interacts with complement proteins, possibly via glycan motifs.", "mechanism": "AAV capsid proteins activate complement, leading to thrombocytopenia and microangiopathy.", "protein": "AAV capsid proteins (VP1/VP2/VP3)", "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Heparan sulfate chains are essential for AAV binding and uptake.", "mechanism": "AAV vectors use heparan sulfate proteoglycans for cell entry in gene therapy.", "protein": "Heparan sulfate proteoglycan", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin binding requires proper glycosylation of \u03b1-dystroglycan.", "mechanism": "Laminin binds \u03b1-dystroglycan, stabilizing muscle membrane; loss of dystrophin disrupts this interaction.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12518133" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Upregulation of utrophin partially compensates for dystrophin loss.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC12518133" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "AAVR is a glycoprotein; glycosylation may modulate AAV binding.", "mechanism": "AAVR is a receptor for AAV vectors used in gene therapy for DMD.", "protein": "AAVR (KIAA0319L)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12518133" }, { "confidence": "medium", "disease": "Hemolytic uremic syndrome", "glycan_involvement": "Capsid glycan motifs may interact with complement factors.", "mechanism": "AAV capsid-mediated complement activation can trigger hemolytic uremic syndrome.", "protein": "AAV capsid proteins (VP1/VP2/VP3)", "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosyl glycosylation is required for \u03b1-dystroglycan function and is a readout for therapy.", "mechanism": "Levels of glycosylated \u03b1-dystroglycan reflect DAPC integrity and therapeutic efficacy.", "protein": "Dystroglycan (\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12518133" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Defective N-glycosylation of multiple glycoproteins.", "mechanism": "PMM2 deficiency impairs mannose-1-phosphate production, disrupting N-glycosylation of proteins.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Altered N-glycan structure (hypoglycosylation).", "mechanism": "Abnormal sialotransferrin profile reflects defective N-glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12518987" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Regulates pathways affecting glycoprotein processing and mitochondrial function.", "mechanism": "Circulating miR-122-5p is upregulated, reflecting liver and neurological involvement.", "protein": "miR-122-5p", "relationship_type": "biomarker", "source_pmcid": "PMC12518987" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Impacts glycosylation-related metabolic pathways.", "mechanism": "miR-122-5p is highly liver-specific and dysregulated in PMM2-CDG patients.", "protein": "miR-122-5p", "relationship_type": "biomarker", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "Affects glycoprotein processing in neurons.", "mechanism": "miR-122-5p dysregulation linked to neuronal disease pathways (e.g., oxidative phosphorylation, neurodegeneration).", "protein": "miR-122-5p", "relationship_type": "biomarker", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "Immunological dysfunction/infection susceptibility", "glycan_involvement": "Altered glycosylation impacts immune receptor function.", "mechanism": "Dysregulated miRNA pathways affect FC gamma R-mediated phagocytosis.", "protein": "FC gamma receptor", "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "Endocrine dysfunction", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "miRNA dysregulation affects growth hormone metabolism and signaling.", "protein": "Growth hormone receptor", "protein_enriched": { "function": "Receptor for pituitary gland growth hormone (GH1) involved in regulating postnatal body growth (PubMed:1549776, PubMed:2825030, PubMed:8943276). On ligand binding, couples to the JAK2/STAT5 pathway (P", "gene_name": "GHR", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI" ], "uniprot_id": "P10912" }, "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "Endocrine dysfunction", "glycan_involvement": "N-glycosylation essential for receptor activity.", "mechanism": "miRNA dysregulation impacts insulin signaling and endocrine resistance.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Glycosylation of mitochondrial proteins influences cellular energy and stress response.", "mechanism": "Altered glycosylation affects mitochondrial function and autophagy/mitophagy.", "protein": "Mitochondrial proteins (autophagy/mitophagy related)", "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "medium", "disease": "Neurological disorders/PMM2-CDG", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "miRNA dysregulation impacts ErbB/mTOR/EGFR signaling pathways, affecting neuronal function.", "protein": "ErbB receptor family/EGFR", "relationship_type": "causal", "source_pmcid": "PMC12518987" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APOE structure and receptor interactions.", "mechanism": "APOE \u03b54 increases AD risk, \u03b52 is protective; influences amyloid clearance, lipid metabolism, synaptic plasticity.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC12519502" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates CLU stability and function.", "mechanism": "Altered CSF levels in APOE \u03b54 carriers; involved in amyloid clearance and neuroprotection.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "N-glycosylation may affect complement activation and BBB interaction.", "mechanism": "Elevated in APOE \u03b54 carriers, indicating early BBB impairment.", "protein": "Complement C1r-like protein (C1RL)", "protein_enriched": { "function": "Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum", "gene_name": "C1RL", "glycan_count": 34, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G10486CT", "G27058EU", "G45395BF", "G59626AS", "G70232NH", "G04854VP", "G08918WF", "G31852PQ", "G40574BA", "G40834TG", "G48414YA", "G59324HL", "G62765YT", "G72747WU", "G76868JS", "G84452RH", "G94470IW", "G57321FI", "G43417UB", "G06356OH", "G45495MK", "G64527OM", "G10019LZ", "G22310AV", "G27126ED", "G34730YF", "G41247ZX", "G46691LC", "G56784JY", "G62461SM", "G64394MX", "G83460ZZ" ], "uniprot_id": "Q9NZP8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "N-glycosylation required for CP secretion and copper transport.", "mechanism": "Increased in APOE \u03b54 carriers, associated with BBB dysfunction.", "protein": "Ceruloplasmin (CP)", "relationship_type": "biomarker", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates cell adhesion and signaling.", "mechanism": "Elevated in APOE \u03b52 carriers; promotes synaptic plasticity and neuronal connectivity.", "protein": "Neuronal cell adhesion molecule (NRCAM)", "relationship_type": "protective", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "N-glycosylation influences secretion and synaptic targeting.", "mechanism": "Increased in APOE \u03b52 carriers; supports synapse organization and plasticity.", "protein": "Neuronal pentraxin-1 (NPTX1)", "relationship_type": "protective", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects BDNF stability and receptor binding.", "mechanism": "Higher in APOE \u03b52 carriers; supports neuronal survival and plasticity.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "protective", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for cell adhesion and neural development.", "mechanism": "Elevated in APOE \u03b52 carriers; involved in axonogenesis and synaptic function.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "protective", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor signaling.", "mechanism": "Increased in APOE \u03b52 carriers; regulates synapse organization and plasticity.", "protein": "Ephrin type-A receptor 4 (EPHA4)", "protein_enriched": { "function": "Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway", "gene_name": "EPHA4", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P54764" }, "relationship_type": "protective", "source_pmcid": "PMC12519502" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "N-glycosylation affects VTN interaction with integrins and complement.", "mechanism": "Lower in APOE \u03b52 carriers; associated with improved BBB integrity.", "protein": "Vitronectin (VTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12519502" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Dystrophin is part of the glycoprotein-rich DGC; glycosylation stabilizes complex.", "mechanism": "In-frame deletions in DMD gene produce truncated dystrophin, leading to BMD phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12519546" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Loss destabilizes DGC glycoprotein interactions.", "mechanism": "Out-of-frame DMD mutations cause loss of dystrophin, resulting in severe DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation supports DGC assembly.", "mechanism": "\u03b1-Syntrophin localization depends on dystrophin; truncated dystrophin maintains \u03b1-syntrophin at sarcolemma in BMD.", "protein": "\u03b1-Syntrophin", "protein_enriched": { "function": "Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated", "gene_name": "Clec4e", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9R0Q8" }, "relationship_type": "causal/complex integrity", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation critical for sarcolemma localization.", "mechanism": "\u03b2-Sarcoglycan localization is preserved with truncated dystrophin in BMD model.", "protein": "\u03b2-Sarcoglycan", "relationship_type": "causal/complex integrity", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects DGC-nNOS interaction.", "mechanism": "nNOS mislocalization in DMD due to dystrophin loss, contributing to muscle degeneration.", "protein": "nNOS", "relationship_type": "causal/complex integrity", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Muscle fatigue", "glycan_involvement": "Glycosylation modulates chaperone stability and function.", "mechanism": "Upregulation of heat shock proteins in exercised BMD mice indicates stress response and muscle fatigue.", "protein": "Hspa1a/Hspa1b", "relationship_type": "biomarker", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Muscle regeneration defect", "glycan_involvement": "Glycosylation may affect Grem2 secretion/activity.", "mechanism": "Downregulation of Grem2 in BMD/DMD impairs BMP antagonism, reducing muscle regeneration.", "protein": "Grem2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "N-glycosylation required for peptide maturation.", "mechanism": "Nppa expression used as marker for cardiac stress in BMD/DMD models.", "protein": "Nppa", "relationship_type": "biomarker", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation essential for ECM function.", "mechanism": "Laminin-\u03b12 used to assess extracellular matrix changes; no fibrosis in BMD model.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12519546" }, { "confidence": "medium", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "O-mannosylation required for DGC function.", "mechanism": "\u03b2-Dystroglycan is part of DGC; its glycosylation is critical for complex stability, affected in dystrophinopathies.", "protein": "\u03b2-Dystroglycan", "relationship_type": "complex integrity", "source_pmcid": "PMC12519546" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Likely N-glycosylated; glycosylation may affect stability and synaptic localization.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; associated with synaptic plasticity, tau phosphorylation, and future memory decline.", "protein": "14-3-3\u03b6/\u03b4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Likely N-glycosylated; glycosylation may modulate protein-protein interactions.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; linked to synaptic plasticity and memory impairment.", "protein": "14-3-3\u03b5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation regulates secretion and synaptic clustering.", "mechanism": "Reduced in CSF in A\u03b2+/Tau- and MCI; associated with excitatory synaptic signaling and memory loss.", "protein": "NPTX2", "protein_enriched": { "function": "May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses", "gene_name": "NPTX1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q15818" }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Potential N-glycosylation; may affect vesicle cycle regulation.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; associated with vesicle trafficking and future memory decline.", "protein": "GDI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "O-glycosylation may regulate axonal growth and synaptic plasticity.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; associated with synaptic remodeling and memory decline.", "protein": "GAP-43", "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation may affect synaptic targeting.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; associated with synaptic plasticity and memory impairment.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation may regulate synaptic function.", "mechanism": "Elevated in CSF in A\u03b2+/Tau+ AD; associated with synaptic vesicle exocytosis and memory decline.", "protein": "Complexin-2", "protein_enriched": { "function": "Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles (PubMed:21785414). Organizes the SNAREs into a cross-linked zigza", "gene_name": "CPLX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Reduced in CSF in A\u03b2+/Tau- and MCI; associated with excitatory synaptic clustering and memory loss.", "protein": "NPTXR", "protein_enriched": { "function": "Required for normal Golgi function", "gene_name": "COG6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation may regulate secretion and neurotrophic activity.", "mechanism": "Reduced in CSF in A\u03b2+/Tau- and MCI; associated with neurotrophic signaling and memory loss.", "protein": "VGF", "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation modulates peptide processing and secretion.", "mechanism": "Reduced in CSF in A\u03b2+/Tau- and MCI; associated with neuropeptide secretion and memory loss.", "protein": "Secretogranin-2", "relationship_type": "biomarker", "source_pmcid": "PMC12519626" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for antigenicity and immune targeting.", "mechanism": "Vaccination against GPNMB reduces senescent cell burden and alleviates atherosclerosis.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Metabolic dysfunction", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "GPNMB vaccination improves metabolic parameters and extends lifespan in models.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation modulates T cell interactions.", "mechanism": "CD153 peptide vaccine reduces senescent T cells, improving glucose tolerance and insulin sensitivity.", "protein": "CD153", "protein_enriched": { "function": "Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool", "gene_name": "FTCD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95954" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "Monoclonal antibodies against PD-L1 enhance immune clearance of senescent cells in aging-related diseases.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation influences ligand-receptor interactions.", "mechanism": "PD-L2 blockade promotes removal of senescent cells, reducing inflammation.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates 'don't eat me' signal.", "mechanism": "CD47 blockade enhances immune-mediated clearance of senescent and cancer cells.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for surface expression and CAR recognition.", "mechanism": "CAR-T cells targeting uPAR clear senescent cells, improving fibrosis.", "protein": "uPAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects ligand presentation.", "mechanism": "CAR-T cells targeting NKG2D ligands eliminate senescent and cancer cells.", "protein": "NKG2D ligands", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Secreted glycoproteins drive inflammaging and tissue dysfunction.", "protein": "SASP factors (IL-6, TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Senescence-associated frailty", "glycan_involvement": "Glycoprotein structure essential for enzymatic activity.", "mechanism": "SA-\u03b2-gal activity marks senescent cells in aging tissues.", "protein": "SA-\u03b2-gal", "relationship_type": "biomarker", "source_pmcid": "PMC12520853" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "DSLNT is a disialylated oligosaccharide produced by ST6GalNAc5/6-mediated sialylation.", "mechanism": "DSLNT in human milk protects against NEC in preterm infants; low DSLNT levels are associated with increased NEC risk.", "protein": "DSLNT", "relationship_type": "protective", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "Brain development disorders", "glycan_involvement": "Catalyzes \u03b12,6-sialylation of GalNAc/GlcNAc in gangliosides.", "mechanism": "ST6GalNAc5 is predominantly expressed in adult brain tissue and involved in \u03b1-series ganglioside biosynthesis, essential for brain development.", "protein": "ST6GalNAc5", "protein_enriched": { "function": "Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on t", "gene_name": "ST6GALNAC5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BVH7" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "Brain development disorders", "glycan_involvement": "Catalyzes \u03b12,6-sialylation of GalNAc/GlcNAc in gangliosides.", "mechanism": "ST6GalNAc6 is broadly expressed in nervous tissue and other organs, contributing to ganglioside biosynthesis important for neural function.", "protein": "ST6GalNAc6", "protein_enriched": { "function": "Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc onto glycoproteins and glycolipids, forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer ", "gene_name": "ST6GALNAC6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q969X2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12521282" }, { "confidence": "high", "disease": "Intestinal disorders in preterm infants", "glycan_involvement": "Sialylated glycan structure is essential for protective effect.", "mechanism": "DSLNT supplementation protects rat models from NEC, suggesting a protective role in human infants.", "protein": "DSLNT", "relationship_type": "protective", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "N-glycosylation is required for ST6GalNAc5 activity and stability.", "mechanism": "ST6GalNAc5 catalyzes DSLNT biosynthesis; enhancing its activity may increase protective DSLNT levels in milk.", "protein": "ST6GalNAc5", "protein_enriched": { "function": "Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on t", "gene_name": "ST6GALNAC5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BVH7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "N-glycosylation is required for ST6GalNAc6 activity and stability.", "mechanism": "ST6GalNAc6 catalyzes DSLNT biosynthesis; enhancing its activity may increase protective DSLNT levels in milk.", "protein": "ST6GalNAc6", "protein_enriched": { "function": "Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc onto glycoproteins and glycolipids, forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer ", "gene_name": "ST6GALNAC6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q969X2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "General glycosylation disorders", "glycan_involvement": "Loss of N-glycosylation impairs enzyme function.", "mechanism": "Mutants lacking N-glycosylation show reduced activity and stability, implicating glycosylation defects in disease.", "protein": "ST6GalNAc5", "protein_enriched": { "function": "Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on t", "gene_name": "ST6GALNAC5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BVH7" }, "relationship_type": "causal", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "General glycosylation disorders", "glycan_involvement": "Loss of N-glycosylation impairs enzyme function.", "mechanism": "Mutants lacking N-glycosylation show reduced activity and stability, implicating glycosylation defects in disease.", "protein": "ST6GalNAc6", "protein_enriched": { "function": "Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc onto glycoproteins and glycolipids, forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer ", "gene_name": "ST6GALNAC6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q969X2" }, "relationship_type": "causal", "source_pmcid": "PMC12521282" }, { "confidence": "medium", "disease": "Brain development disorders", "glycan_involvement": "Sialylation of HMOs is essential for neurodevelopment.", "mechanism": "ST6GalNAc4-6 are candidates for HMO biosynthesis in mammary gland, impacting infant brain development.", "protein": "ST6GalNAc4-6", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12521282" }, { "confidence": "low", "disease": "General glycosylation disorders", "glycan_involvement": "N-glycosylation affects enzyme activity.", "mechanism": "ST6Gal1 is involved in sialylation; glycosylation defects may contribute to disease.", "protein": "ST6Gal1", "relationship_type": "causal", "source_pmcid": "PMC12521282" }, { "confidence": "high", "disease": "Macrophage-mediated clearance", "glycan_involvement": "Low terminal sialic acid exposes galactose, increasing lectin-mediated uptake.", "mechanism": "Fibrinogen-rich corona (low sialic acid) promotes recognition and uptake by macrophages.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "high", "disease": "Accelerated hepatic clearance", "glycan_involvement": "Loss of sialic acid triggers asialoglycoprotein receptor-mediated clearance.", "mechanism": "Desialylated fibrinogen in corona exposes galactose, targeting ASGPR in hepatocytes.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "High sialic acid content masks galactose, reducing immune recognition.", "mechanism": "Sialylated fetuin in corona competes for Siglec/lectin binding, reducing NP uptake by immune cells.", "protein": "Fetuin", "relationship_type": "protective", "source_pmcid": "PMC12521558" }, { "confidence": "high", "disease": "Hepatic accumulation", "glycan_involvement": "Desialylation exposes galactose, promoting ASGPR-mediated uptake.", "mechanism": "Asialofetuin in corona increases NP uptake by hepatocytes via ASGPR.", "protein": "Asialofetuin", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "medium", "disease": "Inflammatory response", "glycan_involvement": "Reduced neutral N-glycans may alter immune modulation.", "mechanism": "Low abundance of immunoglobulin-type glycans in corona reduces anti-inflammatory masking.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "medium", "disease": "Altered nanoparticle biodistribution", "glycan_involvement": "Glycosylation pattern affects receptor engagement.", "mechanism": "Plasminogen-rich corona (in high plasma) alters NP-cell interactions and distribution.", "protein": "Plasminogen", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "medium", "disease": "Prolonged circulation half-life", "glycan_involvement": "Sialic acid content provides 'self' signal.", "mechanism": "Albumin-rich, sialylated corona reduces immune recognition, prolonging NP circulation.", "protein": "Serum albumin", "relationship_type": "protective", "source_pmcid": "PMC12521558" }, { "confidence": "medium", "disease": "Cytokine release syndrome", "glycan_involvement": "Glycan profile modulates immune cell activation.", "mechanism": "Corona composition influences cytokine (IL-1\u03b2, TNF-\u03b1) release by macrophages.", "protein": "Histidine-rich glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "low", "disease": "Impaired drug delivery", "glycan_involvement": "Glycosylation affects receptor interactions.", "mechanism": "ApoA-I-rich corona may alter NP targeting and reduce delivery efficiency.", "protein": "Apolipoprotein A-I", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "low", "disease": "Off-target organ toxicity", "glycan_involvement": "Glycan exposure modulates complement binding.", "mechanism": "C1q in corona may trigger complement activation and inflammation.", "protein": "Complement C1q", "relationship_type": "causal", "source_pmcid": "PMC12521558" }, { "confidence": "high", "disease": "Congenital porencephaly", "glycan_involvement": "Glycosylation critical for COL4A1 stability and function in basement membranes.", "mechanism": "COL4A1 mutations disrupt vascular basement membrane, leading to vessel fragility and brain hemorrhage.", "protein": "COL4A1", "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "high", "disease": "Schizencephaly", "glycan_involvement": "Glycosylation affects secretion and assembly of COL4A2 in basement membranes.", "mechanism": "COL4A2 mutations cause vessel wall disruption, leading to cortical malformations.", "protein": "COL4A2", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A2", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G30221QT", "G59324HL", "G29068FM", "G43417UB" ], "uniprot_id": "P08572" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "medium", "disease": "Hydranencephaly", "glycan_involvement": "N-glycosylation required for COL4A1 function in vascular integrity.", "mechanism": "COL4A1 variants cause severe vascular disruption and hemispheric destruction.", "protein": "COL4A1", "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "low", "disease": "Hydranencephaly", "glycan_involvement": "LAMB1 is highly glycosylated; glycosylation affects matrix assembly.", "mechanism": "LAMB1 variant linked to hydranencephaly via basement membrane dysfunction.", "protein": "LAMB1", "relationship_type": "causal (single case)", "source_pmcid": "PMC12521638" }, { "confidence": "medium", "disease": "Fowler syndrome", "glycan_involvement": "Glycosylation may affect FLVCR2 trafficking and function.", "mechanism": "FLVCR2 mutations cause proliferative vasculopathy and hydranencephaly-hydrocephaly.", "protein": "FLVCR2", "protein_enriched": { "function": "Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment (PubMed:18418376). In macrophages of the reticuloendothelial system, is the heme transpor", "gene_name": "SLC48A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6P1K1" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "medium", "disease": "MARCH syndrome", "glycan_involvement": "CEP55 is glycosylated; modification may affect cell division.", "mechanism": "CEP55 mutations cause arrested neuronal mitosis and hydranencephaly.", "protein": "CEP55", "protein_enriched": { "function": "Plays a role in mitotic exit and cytokinesis (PubMed:16198290, PubMed:17853893). Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis (PubMed:17", "gene_name": "CEP55", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q53EZ4" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "high", "disease": "Pseudo-TORCH syndrome", "glycan_involvement": "OCLN glycosylation is essential for tight junction assembly.", "mechanism": "OCLN mutations disrupt tight junctions, leading to brain calcification and polymicrogyria.", "protein": "OCLN", "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "high", "disease": "Intrauterine haemorrhagic destruction", "glycan_involvement": "Glycosylation required for JAM3 cell adhesion function.", "mechanism": "JAM3 mutations cause severe prenatal brain hemorrhage and calcification.", "protein": "JAM3", "protein_enriched": { "function": "Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM2 to regulate different cellular processes (PubMed:11590146, PubMed:11823489). Plays a role in", "gene_name": "JAM3", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G14669DU", "G28541PG", "G28681TP", "G45395BF", "G72735IY", "G80920RR", "G27058EU" ], "uniprot_id": "Q9BX67" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "medium", "disease": "Pseudo-TORCH syndrome-2", "glycan_involvement": "USP18 is glycosylated; modification may affect stability.", "mechanism": "USP18 mutations lead to interferonopathy with brain hemorrhage and calcification.", "protein": "USP18", "protein_enriched": { "function": "E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:23707686, PubMed:24076655,", "gene_name": "ARIH1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4X5" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "medium", "disease": "RNase T2-deficient cystic leukoencephalopathy", "glycan_involvement": "Glycosylation may affect RNASET2 secretion and lysosomal targeting.", "mechanism": "RNASET2 mutations cause white matter cysts and calcification, mimicking CMV infection.", "protein": "RNASET2", "protein_enriched": { "function": "Exhibits a potent RNase activity (PubMed:12244054, PubMed:12527768, PubMed:17150966). Has broad-spectrum antimicrobial activity against many pathogenic microorganisms including uropathogenic E.coli (U", "gene_name": "RNASE7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H1E1" }, "relationship_type": "causal", "source_pmcid": "PMC12521638" }, { "confidence": "high", "disease": "Sleep disorder", "glycan_involvement": "AGP is heavily N-glycosylated; glycosylation affects its anti-inflammatory and immunomodulatory functions.", "mechanism": "Elevated serum AGP is positively associated with sleep disorder prevalence; AGP modulates inflammation and may cross the blood-brain barrier to affect neuroimmune pathways.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Obstructive sleep apnea (OSA)", "glycan_involvement": "N-glycosylation modulates AGP's stability and immune interactions.", "mechanism": "AGP levels are elevated in urine of children with OSA, indicating involvement in inflammatory activation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may affect AGP's ability to interact with immune receptors (e.g., TLR4/CD14).", "mechanism": "Depression mediates 15.1% of the association between AGP and sleep disorders, possibly via inflammation-induced HPA axis disruption.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal/mediator", "source_pmcid": "PMC12522555" }, { "confidence": "high", "disease": "Sleep disorder", "glycan_involvement": "CRP is glycosylated; glycosylation affects its complement activation and inflammatory properties.", "mechanism": "CRP shows a U-shaped association: low levels inversely correlated, high levels positively correlated with sleep disorder risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Sleep disorder", "glycan_involvement": "Albumin glycosylation status may influence its anti-inflammatory capacity.", "mechanism": "Lower albumin levels are associated with higher AGP and increased sleep disorder risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Sleep disorder", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation may affect anti-inflammatory function.", "mechanism": "Sleep deprivation reduces HDL levels; HDL-related inflammation indices are associated with sleep disorder risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Sleep disorder", "glycan_involvement": "CD14 is a glycoprotein; glycosylation affects receptor function and immune signaling.", "mechanism": "Monocyte count is a predictor in sleep disorder models; AGP may activate monocytes via TLR4/CD14.", "protein": "Monocyte count (CD14+)", "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "medium", "disease": "Sleep disorder", "glycan_involvement": "NPS includes AGP and albumin, both glycoproteins; glycosylation status may impact score relevance.", "mechanism": "Higher NPS (includes glycoprotein markers) is positively associated with sleep disorder risk.", "protein": "Naples Prognostic Score (NPS)", "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Altered glycosylation of AGP is linked to metabolic inflammation.", "mechanism": "Higher AGP quartiles are associated with increased diabetes prevalence.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate AGP's vascular effects.", "mechanism": "AGP is a predictor in models including hypertension as a comorbidity.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522555" }, { "confidence": "high", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Correlated with mucin-type O-glycan biosynthesis and glycosaminoglycan pathways.", "mechanism": "Low DHRS7 expression in early STAD; high expression in advanced STAD correlates with poor prognosis via immune evasion and PI3K/AKT/mTOR activation.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "high", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Associated with glycosaminoglycan biosynthesis and degradation.", "mechanism": "High DHRS7 promotes tumor progression by enhancing M2 macrophage infiltration and immunosuppressive TME.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "causal", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Impacts glycan-related metabolic pathways.", "mechanism": "Modulation of DHRS7 alters STAD cell proliferation, migration, and immune infiltration.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "Low DHRS7 expression linked to poor prognosis and increased metastasis.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "DHRS7 deficiency leads to immunosuppressive TME and accelerated tumor progression.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "causal", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Reduced DHRS7 triggers SREBP1 hyperactivation, lipid accumulation, and tumor progression.", "protein": "DHRS7", "protein_enriched": { "function": "NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quino", "gene_name": "DHRS4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BTZ2" }, "relationship_type": "causal", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "N-glycosylation (general for ALB).", "mechanism": "ALB upregulated in STAD tumors and high-risk group.", "protein": "ALB", "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Not specified.", "mechanism": "High CALD1 expression associated with poor prognosis and increased macrophage infiltration.", "protein": "CALD1", "protein_enriched": { "function": "Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates ac", "gene_name": "CALD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q05682" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Not specified.", "mechanism": "High CRABP2 expression linked to poor prognosis and reduced T cell infiltration.", "protein": "CRABP2", "protein_enriched": { "function": "Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors", "gene_name": "CRABP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P29373" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma (STAD)", "glycan_involvement": "Not specified.", "mechanism": "High RIMS1 expression associated with poor prognosis and altered T cell/NK cell infiltration.", "protein": "RIMS1", "protein_enriched": { "function": "Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransm", "gene_name": "RIMS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86UR5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12522653" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "O-glycosylation shields tumor cells from immune recognition.", "mechanism": "Aberrant O-glycosylation of MUC16 inhibits immune synapse formation between NK cells and tumor cells, promoting immune evasion and peritoneal dissemination.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "causal", "source_pmcid": "PMC12523045" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation enhances immune checkpoint function and immune evasion.", "mechanism": "Elevated branched N-glycans on PD-L1 reinforce PD-1/PD-L1 binding, diminishing anti-PD-L1 therapy efficacy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation modulates immune checkpoint engagement.", "mechanism": "Branched N-glycans on tumor cells reinforce PD-1/PD-L1 interaction, reducing immunotherapy efficacy.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Binds to glycan structures on immune checkpoints.", "mechanism": "Galectin-9 interacts with PD-1/TIM-3 axis, mediating T cell exhaustion and shaping immunosuppressive TME.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "causal", "source_pmcid": "PMC12523045" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Sialoglycans on tumor cells engage Siglec-9.", "mechanism": "Siglec-9 on immune cells binds sialoglycan ligands on OC cells, exerting immunosuppressive effects.", "protein": "Siglec-9", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by c", "gene_name": "SIGLEC9", "glycan_count": 5, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G59626AS", "G95865ZB", "G62765YT", "G11101UV", "G56770VP" ], "uniprot_id": "Q9Y336" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation of CD24 is required for Siglec-10 binding.", "mechanism": "CD24 on tumor cells interacts with Siglec-10 on macrophages, inhibiting phagocytosis and promoting immune evasion.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "STn O-glycan is the target epitope.", "mechanism": "TAG72 (STn O-glycan) is highly expressed on OC cells; CAR-T cells targeting TAG72 show potent cytotoxicity.", "protein": "TAG72", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation creates the NGcGM3 epitope.", "mechanism": "CAR-T cells targeting NGcGM3 prevent OC progression with low toxicity.", "protein": "NGcGM3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523045" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "GALNT10 mediates O-glycosylation of multiple proteins.", "mechanism": "High GALNT10 expression predicts poor prognosis, increased regulatory T cells, and decreased granzyme B in CD8+ T cells.", "protein": "GALNT10", "protein_enriched": { "function": "Beta-1,4 N-acetylgalactosaminyltransferase involved in the biosynthesis of Sd(a) histo-blood group antigen. Catalyzes the transfer of N-acetylgalactosamine (GalNAc) group in a beta-1,4-linkage from UD", "gene_name": "B4GALNT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8NHY0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12523045" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Loss of COSMC leads to truncated O-glycans (Tn antigen).", "mechanism": "COSMC knockout induces aberrant O-glycosylation and Tn antigen expression, altering CAR-T cell binding and antitumor activity.", "protein": "COSMC", "protein_enriched": { "function": "Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain ", "gene_name": "ERO1A", "glycan_count": 25, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G11314AS", "G15664MX", "G20579QQ", "G25079LO", "G28681TP", "G31852PQ", "G35029YA", "G39188ZX", "G41247ZX", "G46503DX", "G57317CE", "G62765YT", "G63040RU", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "Q96HE7" }, "relationship_type": "causal", "source_pmcid": "PMC12523045" }, { "confidence": "high", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "HDL is a glycoprotein; glycosylation affects its anti-inflammatory and cholesterol transport functions.", "mechanism": "Low HDL is a diagnostic component of MetS and reflects impaired lipid metabolism.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12523082" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation modulates HDL's anti-inflammatory properties.", "mechanism": "HDL reduces vascular inflammation and is inversely associated with CVD risk.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycosylation status influences its uptake and oxidation.", "mechanism": "Elevated LDL promotes plaque formation in arteries.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Oxidation and glycan modifications enhance LDL immunogenicity and uptake by macrophages.", "mechanism": "OxLDL triggers endothelial dysfunction and atherogenesis.", "protein": "Oxidized LDL (OxLDL)", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used for diabetes diagnosis and monitoring.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "AGEs are formed by non-enzymatic glycation of proteins and lipids.", "mechanism": "AGEs promote vascular stiffening and inflammation, accelerating CVD.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "AGE formation on renal proteins impairs function.", "mechanism": "AGEs accumulate in renal tissue, promoting fibrosis and dysfunction.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Diabetic Neuropathy", "glycan_involvement": "AGE-modified proteins disrupt neuronal function.", "mechanism": "AGEs contribute to nerve damage via oxidative stress and inflammation.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycation of retinal proteins leads to vascular leakage and neovascularization.", "mechanism": "AGEs induce microvascular damage in the retina.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12523082" }, { "confidence": "medium", "disease": "Diabetic Foot", "glycan_involvement": "Altered glycosylation may impair HDL's protective vascular effects.", "mechanism": "Low HDL is associated with increased risk of diabetic foot complications.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12523082" }, { "confidence": "high", "disease": "Non-Small-Cell Lung Carcinoma (NSCLC)", "glycan_involvement": "POSTN is a glycoprotein; glycosylation may affect its stability and interactions in the tumor microenvironment.", "mechanism": "POSTN is expressed in both cancer cells and tumor stroma, correlating with pro-angiogenic factors.", "protein": "Periostin (POSTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12523498" }, { "confidence": "medium", "disease": "Adenocarcinoma (lung)", "glycan_involvement": "Glycosylation of POSTN may modulate its function in cell adhesion and signaling.", "mechanism": "POSTN expression observed in G2 adenocarcinoma tissue, indicating its role in tumor progression.", "protein": "Periostin (POSTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12523498" }, { "confidence": "medium", "disease": "Squamous-cell carcinoma (lung)", "glycan_involvement": "Glycosylation may influence POSTN's interaction with extracellular matrix and angiogenic factors.", "mechanism": "POSTN expression in stroma correlates with VEGF-A, suggesting involvement in angiogenesis.", "protein": "Periostin (POSTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12523498" }, { "confidence": "medium", "disease": "Large-cell carcinoma (lung)", "glycan_involvement": "Glycosylation may affect POSTN's pro-angiogenic activity.", "mechanism": "POSTN expression in stroma correlates with VEGF-A, supporting a role in tumor angiogenesis.", "protein": "Periostin (POSTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12523498" }, { "confidence": "high", "disease": "Non-Small-Cell Lung Carcinoma (NSCLC)", "glycan_involvement": "VEGF-A glycosylation is important for its secretion and activity.", "mechanism": "VEGF-A expression correlates with POSTN in stroma, indicating a pro-angiogenic microenvironment.", "protein": "VEGF-A", "relationship_type": "biomarker", "source_pmcid": "PMC12523498" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation is essential for LRG1 stability and secretion; glycosylation may affect its detection and function as a biomarker.", "mechanism": "LRG1 is secreted at the site of inflammation by neutrophils, hepatocytes, and venules; elevated levels reflect local inflammatory activity.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "Not glycosylated; glycan involvement is not relevant.", "mechanism": "Calprotectin is released by neutrophils during inflammation; its concentration correlates with neutrophil extravasation and intestinal inflammation.", "protein": "Calprotectin (S100A8/A9)", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "medium", "disease": "Bacterial infections", "glycan_involvement": "N-glycosylation required for plasma stability and immune recognition.", "mechanism": "LRG1 is upregulated during bacterial infections as part of the acute-phase response.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "medium", "disease": "Neoplastic processes", "glycan_involvement": "Altered glycosylation may affect LRG1 levels in cancer.", "mechanism": "LRG1 is associated with neoplastic processes, possibly reflecting tumor-associated inflammation.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "high", "disease": "Gastrointestinal inflammation", "glycan_involvement": "Not glycosylated.", "mechanism": "Calprotectin levels rise in GI inflammation due to neutrophil infiltration.", "protein": "Calprotectin (S100A8/A9)", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation affects CRP function and clearance.", "mechanism": "CRP is a systemic marker of inflammation, but less specific than LRG1 or calprotectin for appendicitis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation may influence diagnostic assay performance.", "mechanism": "Serum LRG1 shows higher specificity than CRP/WBC for appendicitis diagnosis.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "Not glycosylated.", "mechanism": "Plasma and fecal calprotectin provide high sensitivity for early appendicitis detection.", "protein": "Calprotectin (S100A8/A9)", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation affects secretion into fluids.", "mechanism": "Urinary and salivary LRG1 are less sensitive but may be highly specific for appendicitis.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation impacts LRG1 detection and function.", "mechanism": "Combining LRG1 and calprotectin with clinical scores may improve diagnostic accuracy.", "protein": "Leucine-rich alpha-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12523658" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Fc glycosylation modulates pharmacokinetics and efficacy", "mechanism": "Blocks PD-1 to restore T cell function and promote antitumor immunity", "protein": "Pembrolizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Removal of core fucose/xylose increases FcRn binding and half-life", "mechanism": "Enhanced FcRn binding and extended serum half-life, potentially improving antitumor efficacy", "protein": "Pembrolizumab (Pembro-XF variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Presence of \u03b21,2-xylose and \u03b11,3-fucose accelerates clearance", "mechanism": "Retains PD-1 binding and antitumor activity but has shorter half-life due to plant-specific glycans", "protein": "Pembrolizumab (Pembro-WT variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "High-mannose glycans associated with faster clearance via mannose receptor", "mechanism": "High-mannose glycoforms result in intermediate half-life; efficacy not directly tested", "protein": "Pembrolizumab (Pembro-KD variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Absence of glycosylation abolishes Fc\u03b3R/C1q binding but preserves FcRn interaction", "mechanism": "Aglycosylated variant retains PD-1 binding and intermediate half-life; lacks ADCC", "protein": "Pembrolizumab (Pembro-NG variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycan composition at Fc modulates FcRn engagement", "mechanism": "FcRn binding prolongs IgG half-life, enhancing therapeutic antibody persistence", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "protective", "source_pmcid": "PMC12523803" }, { "confidence": "medium", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "Glycoengineering to extend half-life may reduce dosing frequency and irAEs", "mechanism": "Frequent dosing due to short half-life increases risk of irAEs", "protein": "Pembrolizumab", "relationship_type": "causal", "source_pmcid": "PMC12523803" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Core-fucosylated glycans typical of mammalian cell production", "mechanism": "Clinically approved anti-PD-1 antibody with mammalian-type glycans; standard efficacy and half-life", "protein": "Pembrolizumab (Keytruda\u00ae)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Human-like glycoforms improve systemic exposure and reduce immunogenicity", "mechanism": "Potential for improved efficacy in other solid tumors due to enhanced pharmacokinetics", "protein": "Pembrolizumab (Pembro-XF variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523803" }, { "confidence": "medium", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "Plant-specific glycans accelerate clearance", "mechanism": "Shorter half-life may necessitate frequent dosing, increasing irAE risk", "protein": "Pembrolizumab (Pembro-WT variant)", "relationship_type": "causal", "source_pmcid": "PMC12523803" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Non-enzymatic glycation of collagen increases AGE formation.", "mechanism": "AGEs cross-link collagen, causing vascular stiffening and dysfunction.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "AGE-modified glycoproteins interact with RAGE.", "mechanism": "AGEs bind RAGE, activating NF-\u03baB and promoting inflammation and insulin resistance.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Non-enzymatic glycation at lysine sites forms AGEs.", "mechanism": "CML and CEL-modified proteins accumulate, impairing renal function.", "protein": "Lysine residues (CML, CEL)", "relationship_type": "biomarker", "source_pmcid": "PMC12523826" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "Glycated hemoglobin (HbA1c) reflects chronic glucose exposure.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Non-enzymatic glycation of albumin.", "mechanism": "Glycated albumin correlates with vascular damage and inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Indirect; acrylamide exposure alters protein function.", "mechanism": "Acrylamide and glycidamide upregulate Rad51, impairing DNA repair and promoting carcinogenesis.", "protein": "Rad51", "protein_enriched": { "function": "Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:223253", "gene_name": "RAD51", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06609" }, "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Indirect; acrylamide exposure affects glycoprotein signaling.", "mechanism": "Acrylamide and glycidamide upregulate EGFR, activating oncogenic pathways.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Indirect; acrylamide modifies protein function.", "mechanism": "Acrylamide exposure reduces BDNF, leading to synaptic loss and cognitive impairment.", "protein": "BDNF", "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Indirect; acrylamide alters protein modification.", "mechanism": "Acrylamide induces Tau hyperphosphorylation, contributing to neuronal dysfunction.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "AGE-modified glycoproteins bind AGE-R1.", "mechanism": "AGEs interact with AGE-R1, modulating immune response and inflammation.", "protein": "OST-48 (AGE-R1)", "relationship_type": "causal", "source_pmcid": "PMC12523826" }, { "confidence": "high", "disease": "High-risk Neuroblastoma", "glycan_involvement": "Sialylation of gangliosides; GD2 is a sialylated glycan structure.", "mechanism": "GD2 is highly expressed on NB cells, especially MYCN-amplified, and targeted by dinutuximab immunotherapy.", "protein": "GD2 (Disialoganglioside)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12523912" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "N-glycan core fucosylation (\u03b1-1,6 linkage).", "mechanism": "Core fucosylation by FUT8 is increased in MYCN-amplified NB and correlates with poor survival.", "protein": "FUT8 (Alpha-1,6-fucosyltransferase)", "protein_enriched": { "function": "Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans", "gene_name": "FUT8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q9BYC5" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12523912" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Upstream enzyme for N-glycan fucosylation.", "mechanism": "MYCN amplification upregulates GMDS, increasing GDP-fucose synthesis and core fucosylation.", "protein": "GMDS (GDP-mannose 4,6-dehydratase)", "protein_enriched": { "function": "Transcription factor specifically required for the formation of motile cilia (PubMed:31630787). Acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. Binds ", "gene_name": "FOXJ1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92949" }, "relationship_type": "causal", "source_pmcid": "PMC12523912" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "O-glycosylation (core 1 structure formation).", "mechanism": "C1GALT1 expression is associated with better survival; loss promotes malignant behavior.", "protein": "C1GALT1 (Core 1 beta1,3-galactosyltransferase)", "relationship_type": "protective", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Polysialylation of NCAM.", "mechanism": "Polysialylated NCAM facilitates NB cell migration and is linked to undifferentiated/high-stage disease.", "protein": "NCAM (Neural Cell Adhesion Molecule)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Sialylation of gangliosides (GD2 synthesis).", "mechanism": "ST8SIA1 regulates GD2 expression; low expression linked to mesenchymal NB state and therapy resistance.", "protein": "ST8SIA1 (GD3 synthase)", "protein_enriched": { "function": "Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-lin", "gene_name": "ST8SIA2", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q92186" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "GalNAc-type O-glycosylation.", "mechanism": "O-glycosylation of TrkA by C1GALT1 promotes differentiation and suppresses MYCN expression.", "protein": "TrkA (NTRK1)", "relationship_type": "protective", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Indirectly increases glycosylation substrate pools.", "mechanism": "HK2 upregulated by MYCN, fueling glycolysis and hexosamine pathway for glycosylation.", "protein": "HK2 (Hexokinase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Glycosylated transporter; impacts sialylation via metabolic flux.", "mechanism": "MYCN upregulates SLC1A5, increasing glutamine uptake and influencing ST8SIA1 expression.", "protein": "SLC1A5 (ASCT2)", "protein_enriched": { "function": "Sodium-coupled antiporter of neutral amino acids. In a tri-substrate transport cycle, exchanges neutral amino acids between the extracellular and intracellular compartments, coupled to the inward cotr", "gene_name": "SLC1A5", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05049YU", "G06110VR", "G11314AS", "G27058EU", "G39188ZX", "G62765YT", "G70101JE", "G76868JS", "G79666IR", "G80920RR", "G90659AW" ], "uniprot_id": "Q15758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523912" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Indirect; increases substrates for glycan biosynthesis.", "mechanism": "LDHA supports glycolytic flux, indirectly fueling glycosylation pathways.", "protein": "LDHA (Lactate Dehydrogenase A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12523912" }, { "confidence": "high", "disease": "Pediatric heart failure (PHF)", "glycan_involvement": "BNP is glycosylated, which affects its stability and plasma half-life.", "mechanism": "Elevated BNP levels correlate with increased mortality risk in PHF; reflects ventricular wall stress.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Pediatric heart failure (PHF)", "glycan_involvement": "NT-proBNP is glycosylated, influencing its clearance and diagnostic accuracy.", "mechanism": "Elevated NT-proBNP levels are strongly associated with increased mortality risk in PHF; marker of cardiac dysfunction.", "protein": "N-terminal pro-BNP (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Acute heart failure (AHF)", "glycan_involvement": "Glycosylation modulates BNP's stability and immunoreactivity in assays.", "mechanism": "BNP is elevated in acute decompensated heart failure, indicating severe ventricular dysfunction.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Chronic heart failure (CHF)", "glycan_involvement": "Glycosylation affects NT-proBNP's plasma levels and diagnostic cutoffs.", "mechanism": "NT-proBNP is elevated in chronic heart failure, reflecting ongoing myocardial stress.", "protein": "N-terminal pro-BNP (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "medium", "disease": "Pediatric heart failure (PHF)", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans, modulating cell-cell and cell-matrix interactions.", "mechanism": "Galectin-3 is implicated in cardiac fibrosis and remodeling; proposed as a risk stratification marker.", "protein": "Galectin-3", "relationship_type": "biomarker (emerging)", "source_pmcid": "PMC12524215" }, { "confidence": "medium", "disease": "Pediatric heart failure (PHF)", "glycan_involvement": "ST2 is N-glycosylated, which affects its secretion and receptor binding.", "mechanism": "Soluble ST2 reflects myocardial stress and inflammation; potential prognostic marker.", "protein": "ST2 (IL1RL1)", "relationship_type": "biomarker (emerging)", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation influences BNP's stability and detection.", "mechanism": "BNP is elevated in DCM, indicating ventricular dilation and dysfunction.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Congenital heart disease (CHD)", "glycan_involvement": "Glycosylation affects NT-proBNP's diagnostic performance.", "mechanism": "NT-proBNP is elevated in CHD with heart failure, reflecting volume/pressure overload.", "protein": "N-terminal pro-BNP (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation modulates BNP's plasma half-life.", "mechanism": "BNP is elevated in HCM with heart failure, indicating myocardial stress.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation impacts NT-proBNP's stability and clearance.", "mechanism": "NT-proBNP is elevated in HCM, reflecting diastolic dysfunction and increased wall stress.", "protein": "N-terminal pro-BNP (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12524215" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Galectin-9 binds \u03b2-galactoside glycans; its function depends on glycosylation.", "mechanism": "HPV circE7 downregulates LGALS9, suppressing cytotoxic T-cell activity and promoting immune evasion.", "protein": "Galectin-9 (LGALS9)", "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "PD-L1 is N-glycosylated, which stabilizes its expression and immune checkpoint function.", "mechanism": "EBV circBART2.2 binds RIG-I, upregulates PD-L1, promoting tumor immune evasion.", "protein": "PD-L1 (CD274)", "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "FSTL1 is a secreted glycoprotein; glycosylation is essential for secretion and function.", "mechanism": "circ_0004812 sponges miR-1287-5p, upregulates FSTL1, suppressing interferon-induced immune responses.", "protein": "Follistatin-like protein 1 (FSTL1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "TRIM59 may be glycosylated, but direct glycan involvement not specified.", "mechanism": "EBV circLMP2A sponges miR-3908, upregulates TRIM59, promoting proliferation and metastasis.", "protein": "TRIM59", "protein_enriched": { "function": "E3 ubiquitin ligase involved in different processes such as development and immune response (PubMed:22588174, PubMed:30231667). Serves as a negative regulator for innate immune signaling pathways by s", "gene_name": "TRIM59", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8IWR1" }, "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Ebola virus infection", "glycan_involvement": "CLDN18 is a tight junction glycoprotein; glycosylation affects localization/function.", "mechanism": "circRNA-chr19 sponges Ebola miR-30b-3p, upregulates CLDN18, enhancing viral recognition and suppression.", "protein": "CLDN18", "protein_enriched": { "function": "Receptor that may have an important role in cell/cell signaling during nervous system formation", "gene_name": "CELSR1", "glycan_count": 46, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G30970QQ", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G77669RF", "G80920RR", "G07246CJ", "G07755XJ", "G08918WF", "G14972EH", "G27058EU", "G41071NU", "G43223CG", "G79666IR", "G87661QW", "G28681TP", "G63980BQ", "G70101JE", "G83460ZZ", "G49108TO", "G02815KT", "G10486CT", "G59626AS", "G65184UU", "G70619PT", "G72790NZ", "G04657PL", "G39446WN", "G45395BF", "G48584BU", "G57776ZS", "G68490OW", "G70441OD", "G70822IO", "G83646BJ", "G85282JO", "G90659AW", "G27915IV", "G72797UR", "G53434XO", "G29068FM", "G43417UB", "G57321FI", "G15664MX", "G72667IM" ], "uniprot_id": "Q9NYQ6" }, "relationship_type": "protective", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Marek\u2019s disease virus-induced tumors", "glycan_involvement": "Potentially glycosylated; direct glycan role not specified.", "mechanism": "circRUNX2.2 recruits proteins to RUNX2 promoter, enhances transcription, promoting proliferation and inhibiting apoptosis.", "protein": "RUNX2", "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "EEF1A1 may be glycosylated; direct role not specified.", "mechanism": "circ_0050463 sponges miR-33b-5p, upregulates EEF1A1, promoting IAV replication.", "protein": "EEF1A1", "protein_enriched": { "function": "Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:", "gene_name": "EEF1A1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31986NC", "G49108TO", "G41247ZX", "G45395BF", "G80920RR", "G86182NS", "G98611JV" ], "uniprot_id": "P68104" }, "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "B lymphoma (EBV-positive)", "glycan_involvement": "APC may be glycosylated; direct role not specified.", "mechanism": "circEAF2 sponges miR-BART-19, activates APC, suppresses Wnt signaling, inhibits proliferation.", "protein": "APC", "protein_enriched": { "function": "Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity ", "gene_name": "APC", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60923RB", "G49108TO", "G80920RR", "G28905MY" ], "uniprot_id": "P25054" }, "relationship_type": "protective", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Pseudorabies virus infection", "glycan_involvement": "KEAP1 may be glycosylated; direct role not specified.", "mechanism": "circ29164 sponges ssc-miR-24-3p, maintains KEAP1 expression, induces apoptosis, inhibits PRV replication.", "protein": "KEAP1", "relationship_type": "protective", "source_pmcid": "PMC12524399" }, { "confidence": "medium", "disease": "Schwann cell neuropathy (EV71-induced)", "glycan_involvement": "PMP22 is a glycoprotein; glycosylation is critical for myelin function.", "mechanism": "hsa_circ_0069335/miR-29b/PMP22 axis inhibits Schwann cell growth in EV71 infection.", "protein": "PMP22", "protein_enriched": { "function": "Might be involved in growth regulation, and in myelinization in the peripheral nervous system", "gene_name": "PMP22", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q01453" }, "relationship_type": "causal", "source_pmcid": "PMC12524399" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is O-glycosylated; glycosylation is essential for its stability and interaction with the dystrophin-associated glycoprotein complex.", "mechanism": "Disruption of DMD gene by balanced translocation leads to absence of dystrophin protein, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Becker muscular dystrophy", "glycan_involvement": "O-glycosylation affects dystrophin function and complex formation.", "mechanism": "Partial disruption or mutation in DMD gene leads to reduced or abnormal dystrophin, causing milder muscle weakness.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "medium", "disease": "X-linked dilated cardiomyopathy", "glycan_involvement": "Glycosylation status may modulate cardiac dystrophin stability.", "mechanism": "DMD gene mutations affect cardiac muscle dystrophin, leading to cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 18", "glycan_involvement": "Defective glycosylation of muscle proteins due to TRAPPC11 dysfunction.", "mechanism": "Pathogenic variants in TRAPPC11 disrupt glycosylation pathways, leading to muscular dystrophy.", "protein": "TRAPPC11", "protein_enriched": { "function": "May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex", "gene_name": "DCAF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WV16" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Congenital disorders of glycosylation", "glycan_involvement": "Global glycosylation defects in multiple proteins.", "mechanism": "TRAPPC11 mutations impair glycosylation, causing multisystemic symptoms.", "protein": "TRAPPC11", "protein_enriched": { "function": "May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex", "gene_name": "DCAF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WV16" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "medium", "disease": "Ullrich-Bethlem myopathy", "glycan_involvement": "Collagen VI is glycosylated; glycosylation affects extracellular matrix stability.", "mechanism": "COL6A3 variants affect collagen VI structure, leading to muscle weakness.", "protein": "COL6A3", "protein_enriched": { "function": "Structural component of hyaline cartilage and vitreous of the eye", "gene_name": "COL9A2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14055" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "low", "disease": "Autosomal recessive dystonia type 27", "glycan_involvement": "Glycosylation may affect neuronal matrix interactions.", "mechanism": "COL6A3 mutations disrupt neuronal collagen VI, leading to dystonia.", "protein": "COL6A3", "protein_enriched": { "function": "Structural component of hyaline cartilage and vitreous of the eye", "gene_name": "COL9A2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14055" }, "relationship_type": "causal", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restoration of glycoprotein complex requires proper dystrophin glycosylation.", "mechanism": "Gene therapy (microdystrophin via AAV vector) aims to restore dystrophin function and the dystrophin-associated glycoprotein complex.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation status may affect detection sensitivity.", "mechanism": "Absence or reduction of dystrophin detected by immunohistochemistry or genetic testing serves as a diagnostic biomarker.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type 18", "glycan_involvement": "Glycosylation pathway disruption is central to disease mechanism.", "mechanism": "TRAPPC11 mutation status indicates glycosylation defect underlying muscular dystrophy.", "protein": "TRAPPC11", "protein_enriched": { "function": "May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex", "gene_name": "DCAF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WV16" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525165" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Native glycosylation of MOG is required for proper conformational epitope presentation and antibody recognition in live cell-based assays.", "mechanism": "Serum anti-MOG IgG autoantibodies are a defining biomarker for MOGAD diagnosis; titres correlate with clinical and radiological phenotypes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation maintains MOG\u2019s native structure, influencing pathogenic antibody binding.", "mechanism": "Autoantibodies against MOG induce inflammatory demyelination in the CNS, leading to clinical manifestations such as optic neuritis and myelitis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12525177" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Assay specificity depends on glycosylated, conformational MOG epitopes.", "mechanism": "High anti-MOG IgG titres are associated with classical MOGAD presentations (bilateral optic neuritis, encephalic involvement); low titres with atypical features (spinal cord syndromes, MS-like OCBs).", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation ensures epitope integrity for antibody detection.", "mechanism": "Semi-quantitative fluorescence index of anti-MOG IgG stratifies patients by titre, correlating with phenotypic heterogeneity.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation status affects antibody binding specificity.", "mechanism": "Low anti-MOG IgG titres may overlap with MS or other demyelinating disorders, indicating diagnostic ambiguity.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation-dependent epitope recognition may explain cross-reactivity.", "mechanism": "Low-titre anti-MOG IgG can be detected in MS, but typically represents low-affinity/non-pathogenic binding.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "Native glycosylation required for accurate serological discrimination.", "mechanism": "Anti-MOG IgG is rarely present in NMOSD; its detection helps differentiate MOGAD from NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation maintains antigenicity for longitudinal antibody monitoring.", "mechanism": "Persistence of high anti-MOG IgG titres may indicate increased disease activity and lesion burden.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation-dependent epitope presentation affects immunopathological profile.", "mechanism": "High anti-MOG IgG titres are associated with fewer CSF-restricted oligoclonal bands, distinguishing MOGAD from MS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation ensures reliable antibody detection for patient stratification.", "mechanism": "Medium anti-MOG IgG titres are associated with heterogeneous clinical presentations, requiring longitudinal monitoring.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525177" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Defective O-mannosyl glycosylation impairs dystroglycan function.", "mechanism": "Altered dystroglycan binding and ECM organization in DMD; impacts muscle integrity.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "medium", "disease": "LGMD", "glycan_involvement": "Alters sulfation pattern of heparan sulfate glycosaminoglycans.", "mechanism": "Heparan sulfate modification enzyme found in disease-proximal clusters; may affect ECM signaling.", "protein": "HS3ST3A1", "protein_enriched": { "function": "May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/", "gene_name": "DLGAP4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G19163FX", "G49108TO" ], "uniprot_id": "Q9Y2H0" }, "relationship_type": "candidate pathogenic factor", "source_pmcid": "PMC12525345" }, { "confidence": "medium", "disease": "ALS (FUS mutation)", "glycan_involvement": "Modifies glycosaminoglycan sulfation, impacting ECM-neuron interactions.", "mechanism": "Shared cluster proximity in ALS_FUS and LGMD; suggests role in ECM and neuronal signaling.", "protein": "HS3ST3A1", "protein_enriched": { "function": "May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/", "gene_name": "DLGAP4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G19163FX", "G49108TO" ], "uniprot_id": "Q9Y2H0" }, "relationship_type": "candidate pathogenic factor", "source_pmcid": "PMC12525345" }, { "confidence": "medium", "disease": "LGMD", "glycan_involvement": "Catalyzes N-glycan sialylation, modulating cell\u2013cell and ECM interactions.", "mechanism": "High-scoring isolated DEG in LGMD_myob; sialylation may affect muscle cell surface properties.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "medium", "disease": "DMD", "glycan_involvement": "Collagen glycosylation affects fibril formation and ECM stability.", "mechanism": "Collagen binding enriched in DMD datasets; reflects ECM remodeling in dystrophic muscle.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "medium", "disease": "DMD", "glycan_involvement": "N-glycosylation modulates cadherin adhesive function.", "mechanism": "Shared isolated DEG in DMD_pCard and DMD_cfib; cadherin-mediated adhesion altered in DMD.", "protein": "CDH12", "protein_enriched": { "function": "Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity (PubMed:11485571, PubMed:32822537). Could also use ITP as phosphate donor (PubMed:11485571). Its physiological functi", "gene_name": "AK3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9UIJ7" }, "relationship_type": "candidate biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "low", "disease": "DMD", "glycan_involvement": "Potential O-glycosylation affects actin binding and cell structure.", "mechanism": "Clustered with DMD in cardiac fibroblast dataset; involved in cytoskeletal organization.", "protein": "ANLN", "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "low", "disease": "LGMD", "glycan_involvement": "Glycosylation may regulate enzyme stability and activity.", "mechanism": "Over-expressed in LGMD_myob; involved in muscle cell differentiation and oxidative stress.", "protein": "GSTM1", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prost", "gene_name": "GSTM1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09488" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "low", "disease": "LGMD", "glycan_involvement": "Glycosylation modulates inhibitory function.", "mechanism": "Immune-related DEG in LGMD_pbmc; regulates protease activity in inflammation.", "protein": "SERPINB2", "protein_enriched": { "function": "Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1", "gene_name": "SERPINB2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05120" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "low", "disease": "LGMD", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Matrix remodeling enzyme upregulated in LGMD_pbmc; contributes to ECM turnover.", "protein": "MMP1", "relationship_type": "biomarker", "source_pmcid": "PMC12525345" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Altered Fc N-glycosylation (decreased galactosylation/sialylation, increased fucosylation) correlates with inflammation.", "mechanism": "ACPA IgG is a diagnostic marker for RA; its effector functions are modulated by Fc glycosylation.", "protein": "ACPA IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Lower galactosylation/sialylation promotes pro-inflammatory activity.", "mechanism": "Decreased galactosylation and sialylation of IgG1 ACPA correlates with higher inflammatory markers (CRP, ESR, RF).", "protein": "IgG1 (ACPA)", "relationship_type": "causal", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Higher fucosylation reduces ADCC potential.", "mechanism": "Increased core-fucosylation of IgG1 ACPA compared to healthy controls may affect Fc\u03b3RIIIa binding and ADCC.", "protein": "IgG1 (ACPA)", "relationship_type": "causal", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Lower fucosylation increases Fc\u03b3RIIIa affinity.", "mechanism": "ACPA IgG2 shows lower fucosylation compared to healthy controls, potentially enhancing ADCC.", "protein": "IgG2 (ACPA)", "relationship_type": "causal", "source_pmcid": "PMC12525468" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Lower galactosylation/sialylation indicates higher disease activity.", "mechanism": "Galactosylation and sialylation of non-ACPA IgG1 negatively correlate with disease activity score (DAS) and inflammatory markers.", "protein": "Non-ACPA IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Bisecting GlcNAc promotes antibody-dependent cell-mediated cytotoxicity.", "mechanism": "Increased bisecting GlcNAc in non-ACPA IgG1 compared to ACPA and healthy controls may enhance ADCC.", "protein": "Non-ACPA IgG1", "relationship_type": "causal", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Fucosylated glycoforms associate with disease activity.", "mechanism": "Relative abundance of specific fucosylated glycans (N4H3F1, N4H4F1, N4H4S1F1, N5H3F1) in IgG3/4 correlates positively with DAS.", "protein": "IgG3/4 (ACPA and non-ACPA)", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Lower galactosylation reduces Fc\u03b3RIII binding, promoting immune activation.", "mechanism": "Decreased galactosylation is a hallmark of inflammation in RA and other autoimmune diseases.", "protein": "IgG (bulk)", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Lower galactosylation is a marker of autoimmune inflammation.", "mechanism": "Decreased galactosylation observed in SLE, indicating inflammation.", "protein": "IgG (bulk)", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "medium", "disease": "Myasthenia gravis", "glycan_involvement": "Lower galactosylation is a marker of autoimmune inflammation.", "mechanism": "Decreased galactosylation observed in MG, indicating inflammation.", "protein": "IgG (bulk)", "relationship_type": "biomarker", "source_pmcid": "PMC12525468" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation", "glycan_involvement": "Defective N-glycosylation due to reduced manganese-dependent glycosyltransferase activity.", "mechanism": "Loss-of-function mutations in SLC39A8 cause manganese deficiency, impairing glycosyltransferase activity and glycoprotein biosynthesis.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "causal", "source_pmcid": "PMC12525855" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Secondary hypoglycosylation affects glycoproteins involved in lipid transport and vascular health.", "mechanism": "SNP rs13107325 reduces ZIP8 function, leading to hypoglycosylation and altered lipid metabolism, increasing CVD risk.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "causal", "source_pmcid": "PMC12525855" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Reduced glycosyltransferase activity impacts glycoproteins regulating metabolism.", "mechanism": "rs13107325 is associated with increased BMI and adiposity, possibly via impaired glycosylation and metabolic enzyme function.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "causal", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Hypoglycosylation of lipoproteins may increase atherogenicity.", "mechanism": "Impaired ZIP8 function alters lipid profiles and increases atherogenic lipoprotein particles.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "causal", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "VWF glycosylation status affects its plasma levels and function.", "mechanism": "rs13107325 is associated with elevated plasma VWF, a marker of endothelial dysfunction and CVD risk.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Acute coronary syndrome", "glycan_involvement": "Glycosylation affects NT-proBNP stability and secretion.", "mechanism": "rs13107325 is linked to elevated NT-proBNP, predicting higher risk of cardiovascular death.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation defects may impact immune cell signaling.", "mechanism": "rs13107325 is associated with increased risk of Crohn's disease, possibly via altered immune glycoprotein function.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "causal", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates ApoA function and HDL metabolism.", "mechanism": "rs13107325 is associated with lower ApoA and HDL, indicating impaired reverse cholesterol transport.", "protein": "Apolipoprotein A (ApoA)", "relationship_type": "biomarker", "source_pmcid": "PMC12525855" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "CRP glycosylation affects its inflammatory activity.", "mechanism": "Dietary manganese is associated with lower CRP, indicating reduced inflammation and CVD risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525855" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation of NT-proBNP influences its plasma levels.", "mechanism": "Elevated NT-proBNP (linked to rs13107325) is associated with increased stroke risk.", "protein": "ZIP8 (SLC39A8)", "protein_enriched": { "function": "Transporter for the divalent cation Zn(2+) (PubMed:10681536, PubMed:29791142, PubMed:30914478). Mediates the influx of Zn(2+) into cells from extracellular space. The Zn(2+) uniporter activity is inde", "gene_name": "SLC39A2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G72065MN" ], "uniprot_id": "Q9NP94" }, "relationship_type": "biomarker", "source_pmcid": "PMC12525855" }, { "confidence": "high", "disease": "colitis", "glycan_involvement": "Altered O-glycosylation reduces mucin protective function.", "mechanism": "Muc2 deficiency leads to loss of mucus barrier, allowing bacteria to invade epithelium and trigger colitis.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "colorectal cancer", "glycan_involvement": "Defective glycosylation impairs barrier, increasing cancer risk.", "mechanism": "Chronic inflammation from Muc2 loss promotes carcinogenesis.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "type 2 diabetes", "glycan_involvement": "Altered mucin glycosylation reflects metabolic state.", "mechanism": "HFD-induced reduction in Muc2 correlates with metabolic dysfunction.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "cardiovascular disease", "glycan_involvement": "Glycosylation changes signal barrier dysfunction.", "mechanism": "Western diet reduces Muc2, associated with increased cardiovascular risk.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "metabolic syndrome", "glycan_involvement": "Sialylation/sulfation changes reflect metabolic stress.", "mechanism": "Reduced Muc2 expression and altered glycosylation linked to metabolic syndrome features.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12526196" }, { "confidence": "high", "disease": "colitis", "glycan_involvement": "Restores O-glycosylation, sialylation, and sulfation of mucins.", "mechanism": "Chickpea (MG_13) supplementation restores Muc2 levels, improving barrier and reducing inflammation.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "colorectal cancer", "glycan_involvement": "Improved glycosylation supports barrier integrity.", "mechanism": "Chickpea supplementation may reduce carcinogenesis risk by restoring mucin barrier.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "GalNAc increase in disease state; decrease under HFD.", "mechanism": "Altered GalNAc residues in mucins associated with Crohn's disease.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "colitis", "glycan_involvement": "Targeting O-glycosylation pathways.", "mechanism": "Restoring mucin glycosylation (e.g., sialylation, fucosylation) may prevent or treat colitis.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12526196" }, { "confidence": "medium", "disease": "colitis", "glycan_involvement": "Sialylation and GlcNAc modifications as markers of disease state.", "mechanism": "Sialic acid and GlcNAc levels in mucins reflect barrier integrity and inflammation.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12526196" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "IgG glycosylation modulates Fc receptor and complement binding.", "mechanism": "IgG autoantibodies form immune complexes that deposit in tissues, activating complement and causing inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Altered IgG Fc glycosylation enhances pro-inflammatory activity.", "mechanism": "IgG (especially ACPA) forms immune complexes in joints, activating Fc\u03b3 receptors and complement, driving inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "ANCA-associated vasculitis", "glycan_involvement": "Fc glycosylation affects Fc\u03b3R binding and effector function.", "mechanism": "IgG autoantibodies (ANCA) activate neutrophils via Fc\u03b3R, causing vascular injury.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "IgG-mediated autoimmune diseases", "glycan_involvement": "FcRn binding to IgG is glycan-dependent; glycosylation affects affinity.", "mechanism": "FcRn recycles IgG, prolonging its half-life; inhibition accelerates IgG clearance.", "protein": "FcRn (neonatal Fc receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12527857" }, { "confidence": "medium", "disease": "IgG4-related disease", "glycan_involvement": "IgG4 glycosylation may modulate immune complex formation and effector function.", "mechanism": "Elevated IgG4 and IgG4+ plasma cells infiltrate tissues, causing fibrosis and organ dysfunction.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation of \u03b22-GPI influences antibody binding.", "mechanism": "IgG anti-\u03b22-GPI antibodies form immune complexes, activating coagulation and complement, leading to thrombosis.", "protein": "\u03b22-Glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "medium", "disease": "Pemphigus vulgaris", "glycan_involvement": "Desmoglein glycosylation may affect autoantibody recognition.", "mechanism": "IgG autoantibodies target desmoglein 1/3, disrupting cell adhesion and causing blistering.", "protein": "Desmoglein 1/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "low", "disease": "IgG4-related disease", "glycan_involvement": "Galectin-3 is a glycan-binding protein; glycosylation modulates its function.", "mechanism": "IgG4 autoantibodies against galectin-3 detected in some patients.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12527857" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis", "glycan_involvement": "MPO glycosylation may influence antigenicity.", "mechanism": "IgG anti-MPO antibodies activate neutrophils, causing vasculitis.", "protein": "MPO (Myeloperoxidase)", "relationship_type": "causal", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "Myasthenia gravis", "glycan_involvement": "IgG glycosylation affects FcRn binding and recycling.", "mechanism": "FcRn inhibition reduces pathogenic IgG, improving symptoms.", "protein": "FcRn (neonatal Fc receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12527857" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Altered N-glycosylation (galactosylation, sialylation) modulates inflammatory potential.", "mechanism": "IgG accumulates in aged tissues, induces cell senescence, and tissue aging.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Altered glycosylation may affect IgG function in AD.", "mechanism": "Increased IgG binding to senescent erythrocytes via band 3 antigen; reflects neurodegeneration.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation changes linked to disease severity.", "mechanism": "IgG treatment alleviates arterial stiffening and hypertension in aged mice.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12528134" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "IgM (especially anti-PC) reduces atherosclerosis progression and cardiovascular events.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Not specified.", "mechanism": "Lower serum IgM in centenarians predicts shorter survival; increased IgM may be anti-aging.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "N- and O-glycosylation sites change with age; functional impact unclear.", "mechanism": "Serum and tissue IgA increase with age; interacts with gut microbiota to modulate inflammation and senescence.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Food allergy", "glycan_involvement": "Not specified.", "mechanism": "IgE increases in elderly skin lesions, promoting allergic inflammation.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "IgE promotes macrophage polarization and cholesterol accumulation; deficiency attenuates disease.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "IgD\u2212CD27\u2212 B cells increased in severe atherosclerosis, promote inflammation in elderly males.", "protein": "Immunoglobulin D (IgD)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHD", "glycan_count": 57, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G29068FM", "G43417UB", "G07617FP", "G56014GC", "G68668TB", "G06356OH", "G22310AV", "G26403SG", "G31665QC", "G48414YA", "G82830MN", "G86795LJ", "G89205CJ", "G00031MO", "G01614ZM", "G02030ZB", "G03382KH", "G05724UK", "G06110VR", "G12708JQ", "G22140GZ", "G23432EQ", "G23453IV", "G23863VK", "G24835MQ", "G27993JQ", "G29880MM", "G29931IJ", "G39188ZX", "G43157UW", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G55220VL", "G56682BC", "G56903ZB", "G57818FI", "G61627IG", "G61937QU", "G64527OM", "G65562ZE", "G66676MI", "G66760KM", "G68698AP", "G70101JE", "G72667IM", "G74722FL", "G75798PH", "G79568CQ", "G80966KZ", "G81006GJ", "G81295CK", "G82020ZR", "G84452RH", "G91473PK", "G91636VS" ], "uniprot_id": "P01880" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528134" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "Band 3 degradation produces senescent cell antigen, increasing IgG binding to erythrocytes in AD.", "protein": "Band 3 protein", "protein_enriched": { "function": "Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein (PubMed:10926824, PubMed:14734552, PubMed:1538405, PubMed:16227998, Pub", "gene_name": "SLC4A1", "glycan_count": 50, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G00912UN", "G01650EU", "G03644CB", "G05049YU", "G06110VR", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G16125XL", "G18647XP", "G23719VF", "G27058EU", "G27915IV", "G27947YN", "G28541PG", "G28622IK", "G30970QQ", "G35029YA", "G37399XV", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G47644PP", "G49906RN", "G57776ZU", "G59626AS", "G60033FS", "G65184UU", "G72787SB", "G72790NZ", "G75568BH", "G79666IR", "G80479JV", "G83646BJ", "G85282JO", "G85554PZ", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G98611JV" ], "uniprot_id": "P02730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12528134" }, { "confidence": "high", "disease": "Equine obesity", "glycan_involvement": "Glycosylation required for Fetuin-A secretion and function.", "mechanism": "Elevated Fetuin-A levels in liver, adipose tissue, and serum are associated with obesity; Fetuin-A inhibits insulin receptor activity and promotes inflammation.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates Fetuin-A stability and receptor interactions.", "mechanism": "Fetuin-A inhibits insulin receptor tyrosine kinase activity, reducing insulin sensitivity in peripheral tissues.", "protein": "Fetuin-A (AHSG)", "relationship_type": "causal", "source_pmcid": "PMC12528206" }, { "confidence": "medium", "disease": "Equine metabolic syndrome (EMS)", "glycan_involvement": "Glycosylation essential for Fetuin-A's metabolic effects.", "mechanism": "Elevated Fetuin-A may contribute to insulin dysregulation and metabolic syndrome development.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects Fetuin-A secretion from liver.", "mechanism": "High Fetuin-A levels correlate with hepatic lipid accumulation and inflammation.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation influences Fetuin-A's inhibitory activity.", "mechanism": "Fetuin-A inhibits insulin signaling, contributing to glucose intolerance and T2DM risk.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528206" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "Glycosylation required for Fetuin-A's endocrine effects.", "mechanism": "Elevated Fetuin-A levels are associated with insulin resistance and metabolic features of PCOS.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker", "source_pmcid": "PMC12528206" }, { "confidence": "medium", "disease": "Laminitis", "glycan_involvement": "Glycosylation impacts Fetuin-A's inflammatory role.", "mechanism": "Obesity and insulin dysregulation (with high Fetuin-A) increase laminitis risk.", "protein": "Fetuin-A (AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Equine obesity", "glycan_involvement": "FBXW7 targets phosphorylated (and glycosylated) Fetuin-A for ubiquitination.", "mechanism": "FBXW7 mediates Fetuin-A degradation; its depletion in obesity leads to Fetuin-A accumulation and metabolic dysfunction.", "protein": "FBXW7", "protein_enriched": { "function": "Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubM", "gene_name": "FBXW7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969H0" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "FBXW7 recognizes glycosylated Fetuin-A for degradation.", "mechanism": "Exogenous FBXW7 reduces Fetuin-A levels and restores insulin receptor phosphorylation, improving insulin sensitivity.", "protein": "FBXW7", "protein_enriched": { "function": "Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubM", "gene_name": "FBXW7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969H0" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Inflammation (systemic, obesity-related)", "glycan_involvement": "Glycosylation required for Fetuin-A's interaction with TLR4.", "mechanism": "Fetuin-A activates TLR4/NF-\u03baB/MAPK axis, increasing pro-inflammatory cytokines (IL-1\u03b2, TNF-\u03b1).", "protein": "Fetuin-A (AHSG)", "relationship_type": "causal", "source_pmcid": "PMC12528206" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is a glycoprotein; glycosylation affects membrane stability.", "mechanism": "Loss-of-function mutations in dystrophin gene cause DMD, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12528695" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation modulates dystrophin's interaction with other membrane proteins.", "mechanism": "Deficiency or absence of dystrophin disrupts muscle fiber integrity.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Myomaker is a glycoprotein; glycosylation may regulate fusogenic activity.", "mechanism": "Used as a fusogen to direct gene editing tools to muscle cells for therapy.", "protein": "Myomaker", "protein_enriched": { "function": "", "gene_name": "Zfp759", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8C0P2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation may influence membrane fusion efficiency.", "mechanism": "Facilitates membrane fusion for muscle-specific delivery of gene editors.", "protein": "Myomerger", "protein_enriched": { "function": "Acts as an adapter for the myotubularin-related phosphatases (PubMed:23818870). Regulates phosphatase MTM1 protein stability and possibly its intracellular location (PubMed:23818870). By stabilizing M", "gene_name": "Mtmr12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q80TA6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Integrin glycosylation affects cell adhesion and signaling.", "mechanism": "\u03b17-Integrin+ myogenic cells are used to identify muscle progenitors for targeted therapy.", "protein": "\u03b17-Integrin", "relationship_type": "biomarker", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Respiratory failure", "glycan_involvement": "Glycosylation maintains dystrophin function in muscle membranes.", "mechanism": "Dystrophin deficiency in diaphragm muscle leads to respiratory complications.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12528695" }, { "confidence": "high", "disease": "Muscle degeneration", "glycan_involvement": "Glycosylation stabilizes dystrophin's membrane association.", "mechanism": "Absence of dystrophin results in progressive muscle fiber damage.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Altered glycosylation may exacerbate fibrosis.", "mechanism": "Dystrophin loss leads to muscle injury and fibrotic tissue replacement.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Respiratory failure", "glycan_involvement": "Glycosylation may affect Myomaker's targeting specificity.", "mechanism": "MuVLPs targeting Myomaker restore dystrophin in diaphragm, improving respiratory function.", "protein": "Myomaker", "protein_enriched": { "function": "", "gene_name": "Zfp759", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8C0P2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12528695" }, { "confidence": "medium", "disease": "Muscle degeneration", "glycan_involvement": "Glycosylation may modulate fusogenic activity.", "mechanism": "MuVLPs using Myomerger enhance gene delivery to muscle cells, reducing degeneration.", "protein": "Myomerger", "protein_enriched": { "function": "Acts as an adapter for the myotubularin-related phosphatases (PubMed:23818870). Regulates phosphatase MTM1 protein stability and possibly its intracellular location (PubMed:23818870). By stabilizing M", "gene_name": "Mtmr12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q80TA6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12528695" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Downregulation of N-glycosylation at multiple sites (N324, N613, N781, N998).", "mechanism": "Reduced N-glycosylation impairs calcium channel function, disrupting neuronal calcium homeostasis and synaptic transmission.", "protein": "CACNA2D1", "protein_enriched": { "function": "The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type", "gene_name": "CACNA2D2", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G41247ZX", "G62765YT", "G72787SB", "G80920RR", "G26436YP", "G83460ZZ" ], "uniprot_id": "Q9NY47" }, "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "All three N-glycosylation sites downregulated (>1.5-fold).", "mechanism": "Decreased N-glycosylation impairs GABAergic inhibitory neurotransmission, contributing to synaptic dysfunction.", "protein": "GABRA3", "protein_enriched": { "function": "Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:16412217, PubMed:29053855). GABA-g", "gene_name": "GABRA3", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G84259QT", "G83460ZZ", "G09700PF" ], "uniprot_id": "P34903" }, "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Downregulation of N-glycosylation at APRs.", "mechanism": "Loss of N-glycosylation at APRs in NMDA receptor impairs synaptic transmission and may promote aggregation.", "protein": "GRIN1", "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Elevated N-glycosylation in AD brain.", "mechanism": "Upregulated N-glycosylation may disrupt cholesterol homeostasis, influencing amyloid-beta accumulation.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Elevated N-glycosylation in AD brain.", "mechanism": "Increased N-glycosylation may alter cholesterol efflux and amyloid-beta clearance.", "protein": "LRP2", "protein_enriched": { "function": "Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such a", "gene_name": "LRP2", "glycan_count": 192, "glycosylation_sites_count": 40, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G57321FI", "G01485JJ", "G04657PL", "G07246CJ", "G07755XJ", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15664MX", "G16125XL", "G23719VF", "G27058EU", "G27915IV", "G28622IK", "G29545VG", "G31852PQ", "G35541EV", "G36379GD", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G49755GI", "G54010QB", "G59626AS", "G60033FS", "G60834IK", "G62765YT", "G68490OW", "G69521XL", "G70223PD", "G72747WU", "G77669RF", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G83633GK", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G95177YH", "G95865ZB", "G00273SJ", "G00912UN", "G01160VV", "G02528FI", "G03644CB", "G05049YU", "G05962QB", "G06247RL", "G10846ZT", "G12341GU", "G14547CB", "G20528HD", "G27947YN", "G30221QT", "G30740WO", "G30970QQ", "G32788FZ", "G37818NZ", "G39471UU", "G40574BA", "G40926MX", "G43669FQ", "G44753VC", "G45504EY", "G46503DX", "G46691LC", "G49906RN", "G50856PC", "G51653BI", "G53075ES", "G55132BD", "G56518TU", "G57776ZS", "G65414LI", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G75568BH", "G75983OB", "G77547TA", "G79666IR", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G90382BL", "G90659AW", "G93718GY", "G94665LC", "G98611JV", "G99668VU", "G02815KT", "G02886BB", "G07810QS", "G08290VR", "G10486CT", "G11314AS", "G18647XP", "G28541PG", "G28681TP", "G35029YA", "G37399XV", "G37509XX", "G43769HG", "G47644PP", "G49955PK", "G57317CE", "G57776ZU", "G58954YZ", "G59924QI", "G65184UU", "G72787SB", "G72790NZ", "G76295SF", "G85269DF", "G92275SC", "G92406TI", "G10488MI", "G20706XG", "G24528MX", "G78787DI", "G04854VP", "G72197KC", "G92551JA", "G39446WN", "G92050GC", "G96091TT", "G01650EU", "G17208MA", "G27126ED", "G34989PA", "G49018RC", "G90734RJ", "G25079LO", "G26330YA", "G35253PZ", "G37995HC", "G63041LO", "G64409MC", "G87389XI", "G23505EP", "G31986NC", "G34029GR", "G37412TK", "G40834TG", "G58087IP", "G73968GN", "G84349RE", "G88891KO", "G96430BV", "G29184RN", "G31028YV", "G40206WX", "G47702MW", "G47950XN", "G75418YA", "G12261QD", "G84862VB", "G29299MO", "G36442WJ", "G41840AI", "G50282JC", "G61256FT", "G90575OW", "G06110VR", "G59536GA", "G63980BQ", "G83229XP", "G68735SN", "G84225JN", "G71463BG", "G71142DF", "G05724UK", "G49642SA", "G63136LV" ], "uniprot_id": "P98164" }, "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N337 site upregulated (>1.5-fold).", "mechanism": "Upregulated N-glycosylation at N337 may modulate \u03b3-secretase cleavage, influencing plaque formation.", "protein": "APLP1", "protein_enriched": { "function": "May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding (By similarity). Couples to JIP sign", "gene_name": "APLP1", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G59324HL" ], "uniprot_id": "P51693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N499 and N518 sites upregulated.", "mechanism": "Upregulated N-glycosylation at N499 and N518 associated with age and cognitive decline severity.", "protein": "ALCAM", "relationship_type": "biomarker", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N300 site within APR downregulated.", "mechanism": "Downregulation of N-glycosylation at APR (N300) may promote aggregation and plaque formation.", "protein": "LSAMP", "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N143 site within APR downregulated.", "mechanism": "Reduced N-glycosylation at APR (N143) may decrease solubility, promoting aggregation in plaques.", "protein": "HLA-DRA", "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "All four N-glycosylation sites upregulated.", "mechanism": "Upregulated N-glycosylation may contribute to choline metabolism imbalance in AD.", "protein": "ENPP6", "protein_enriched": { "function": "Choline-specific phosphodiesterase that hydrolyzes sphingomyelin releasing the ceramide and phosphocholine and therefore is involved in sphingomyelin digestion, ceramide formation, and fatty acid (FA)", "gene_name": "ENPP7", "glycan_count": 14, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G10486CT", "G42124LM", "G72790NZ", "G01650EU", "G37399XV", "G41840AI", "G59924QI", "G62765YT", "G80920RR", "G41247ZX", "G14972EH", "G43223CG", "G87661QW" ], "uniprot_id": "Q6UWV6" }, "relationship_type": "causal", "source_pmcid": "PMC12529471" }, { "confidence": "high", "disease": "muscular dystrophies (alpha-dystroglycanopathies)", "glycan_involvement": "Loss or abnormal O-mannosyl glycans (including ribitol-5-phosphate containing core M3 glycans) on \u03b1-DG impairs its function.", "mechanism": "Defective glycosylation of \u03b1-DG disrupts cell-matrix interactions, leading to muscle pathology.", "protein": "alpha-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12532225" }, { "confidence": "high", "disease": "Fungal infection (e.g., Candida)", "glycan_involvement": "Direct; \u03b2-(1,3)-glucan structure is essential for immune recognition.", "mechanism": "\u03b2-(1,3)-glucans are present on fungal cell surfaces and serve as pathogen-associated molecular patterns (PAMPs) recognized during infection.", "protein": "\u03b2-(1,3)-glucan", "relationship_type": "biomarker", "source_pmcid": "PMC12532290" }, { "confidence": "high", "disease": "Fungal infection (e.g., Candida)", "glycan_involvement": "Antibody recognizes \u03b2-(1,3)-glucan glycan epitope.", "mechanism": "Anti-\u03b2-glucan antibodies indicate exposure to fungal \u03b2-glucans and are used for early diagnosis.", "protein": "Anti-\u03b2-glucan antibody (mouse monoclonal, IgG2b, 2G8)", "relationship_type": "biomarker", "source_pmcid": "PMC12532290" }, { "confidence": "high", "disease": "Fungal infection (e.g., Candida)", "glycan_involvement": "Antibody binds \u03b2-(1,3)-glucan glycan structure.", "mechanism": "Anti-\u03b2-glucan antibodies are indicative of fungal infection and aid in diagnosis.", "protein": "Anti-\u03b2-glucan antibody (rabbit monoclonal, IgG1, 8201)", "relationship_type": "biomarker", "source_pmcid": "PMC12532290" }, { "confidence": "medium", "disease": "Fungal infection (e.g., Candida)", "glycan_involvement": "Direct recognition of \u03b2-(1,3)-glucan glycan.", "mechanism": "Dectin-1 recognizes \u03b2-(1,3)-glucans on fungi, triggering immune responses.", "protein": "Dectin-1", "relationship_type": "protective", "source_pmcid": "PMC12532290" }, { "confidence": "medium", "disease": "Fungal infection (e.g., Candida)", "glycan_involvement": "Conformationally modified glycan enhances immune recognition.", "mechanism": "Stapled \u03b2-glucans with constrained conformation show enhanced antibody binding, suggesting potential for vaccine development.", "protein": "Stapled \u03b2-(1,3)-glucan", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12532290" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Apolipoprotein(a) is a glycoprotein; glycosylation affects its structure and function.", "mechanism": "Elevated Lp(a) is an independent risk factor for CHD due to its pro-atherogenic, pro-inflammatory, and pro-thrombotic properties.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation of apolipoprotein(a) modulates Lp(a) properties.", "mechanism": "Lp(a) levels are elevated in some T2DM patients and contribute to increased cardiovascular risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation of apolipoprotein(a) influences Lp(a) atherogenicity.", "mechanism": "Elevated Lp(a) predicts increased risk of CAD, especially in T2DM patients.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12534058" }, { "confidence": "medium", "disease": "Major Adverse Cardiovascular Events (MACEs)", "glycan_involvement": "Glycosylation may affect Lp(a) stability and interactions.", "mechanism": "High Lp(a) levels are associated with increased risk of MACEs in T2DM.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Atherosclerotic Cardiovascular Disease", "glycan_involvement": "Glycosylation of apolipoprotein(a) is essential for its function.", "mechanism": "Lp(a) promotes atherogenesis via pro-inflammatory and pro-thrombotic effects.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "N-glycosylation and O-glycosylation modulate apo(a) structure and Lp(a) assembly.", "mechanism": "Apo(a) is the glycoprotein component of Lp(a) responsible for its pathogenic effects.", "protein": "Apolipoprotein(a)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation may affect therapeutic targeting of Lp(a).", "mechanism": "Statins do not reduce Lp(a) levels; novel therapies (PCSK9 inhibitors, antisense oligonucleotides) are being explored.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534058" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation of apo(a) influences Lp(a) function in diabetes.", "mechanism": "Lp(a) exacerbates diabetic dyslipidemia and increases cardiovascular risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation is part of the genetic regulation of Lp(a) structure.", "mechanism": "Genetically determined high Lp(a) levels are associated with CHD risk, independent of LDL-C and HbA1c.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12534058" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation may influence drug efficacy and Lp(a) clearance.", "mechanism": "PCSK9 inhibitors and antisense oligonucleotides may lower Lp(a) and reduce CHD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534058" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of proteins forms AGEs.", "mechanism": "AGEs accumulate due to hyperglycemia, causing vascular and neural complications.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12534111" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects A\u03b2 aggregation and toxicity.", "mechanism": "A\u03b2 aggregation and glycosylation contribute to neurotoxicity and disease progression.", "protein": "\u03b2-amyloid protein (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12534111" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "RAGE is a glycoprotein receptor for AGEs.", "mechanism": "AGE-RAGE interaction triggers inflammation and oxidative stress.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534111" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation status affects membrane integrity.", "mechanism": "Glycation and oxidative stress damage basement membrane, leading to nephropathy.", "protein": "Glomerular Basement Membrane Proteins", "relationship_type": "causal", "source_pmcid": "PMC12534111" }, { "confidence": "high", "disease": "Cataract", "glycan_involvement": "Non-enzymatic glycation leads to AGE formation in lens proteins.", "mechanism": "Glycation and oxidation of crystallins cause protein aggregation and lens opacity.", "protein": "Lens Crystallins", "relationship_type": "causal", "source_pmcid": "PMC12534111" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects LDL structure and function.", "mechanism": "Glycation and oxidation of LDL promote foam cell formation and plaque development.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12534111" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "MMPs are glycoprotein enzymes.", "mechanism": "MMPs facilitate cancer cell migration and metastasis; carnosine inhibits their activity.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534111" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-cadherin is a glycoprotein involved in cell adhesion.", "mechanism": "N-cadherin promotes epithelial-mesenchymal transition and metastasis; carnosine downregulates its expression.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534111" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Vimentin is glycosylated, affecting cell migration.", "mechanism": "Vimentin is upregulated in metastatic cancer; carnosine reduces its expression.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534111" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Cyclin D1 is glycosylated, influencing stability and function.", "mechanism": "Cyclin D1 regulates cell cycle; carnosine inhibits its expression to block proliferation.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12534111" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Major autoantigen in APS; autoantibodies target \u03b22GPI, contributing to vascular pathology.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Common autoantigen in SLE; autoantibodies to \u03b22GPI correlate with vascular complications.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation required for HDL association and function.", "mechanism": "Regulates HDL cholesterol and ApoE content in females; deficiency leads to increased cholesterol and altered HDL, raising cardiovascular risk.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences HDL binding and immune interactions.", "mechanism": "Deficiency or autoantibody-mediated dysfunction impairs HDL function, increases ApoE-rich HDL, and accelerates atheroma formation, especially in females.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal", "source_pmcid": "PMC12535091" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect adipocyte interactions.", "mechanism": "\u03b22GPI deficiency in females leads to increased visceral adiposity and loss of resistance to obesity, possibly via modulation of ApoE and adipocyte thermogenesis.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal/protective", "source_pmcid": "PMC12535091" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation may affect CNS transport and immune modulation.", "mechanism": "Regulates ApoE-containing HDL particles; deficiency may alter brain lipid homeostasis and neuroinflammation, influencing Alzheimer\u2019s risk in females.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "risk_modifier", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation affects receptor binding and clearance.", "mechanism": "ApoE isoforms modulate neuroinflammation and amyloid processing; increased ApoE in HDL (due to \u03b22GPI deficiency) may impact disease risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12535091" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation may modulate CNS effects.", "mechanism": "Female-specific \u03b22GPI regulation of HDL/ApoE may influence cognitive decline and dementia risk, especially with obesity.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "risk_modifier", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Cardiovascular disease in SLE/APS", "glycan_involvement": "Glycosylation modulates autoantigenicity and HDL binding.", "mechanism": "Autoantibodies to \u03b22GPI impair HDL antioxidant function, increasing cardiovascular risk in female autoimmune patients.", "protein": "\u03b22-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12535091" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects adipocyte receptor interactions.", "mechanism": "ApoE promotes adiposity; \u03b22GPI deficiency increases ApoE in HDL, contributing to increased fat accumulation in females.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12535091" }, { "confidence": "high", "disease": "Circadian syndrome", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP reflects systemic inflammation associated with CircS.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "high", "disease": "Circadian syndrome", "glycan_involvement": "IL-6 is glycosylated, which modulates secretion and receptor binding.", "mechanism": "IL-6 is elevated in CircS, reflecting chronic inflammation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences CRP's inflammatory activity.", "mechanism": "CRP elevation is predictive of CVD risk in CircS.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates IL-6 signaling.", "mechanism": "IL-6 promotes vascular inflammation and atherogenesis.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "medium", "disease": "Circadian syndrome", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting its receptor interactions.", "mechanism": "TNF-\u03b1 is upregulated in CircS, contributing to inflammation.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "medium", "disease": "Sleep disorders", "glycan_involvement": "Glycosylation affects IL-1\u03b2 secretion.", "mechanism": "IL-1\u03b2 increases after sleep deprivation, linking inflammation and sleep disruption.", "protein": "Interleukin-1 beta", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "low", "disease": "Circadian syndrome", "glycan_involvement": "IL-17 is glycosylated, influencing its stability.", "mechanism": "IL-17 is elevated in CircS, reflecting immune activation.", "protein": "Interleukin-17", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect CRP's role in tumor microenvironment.", "mechanism": "CRP is elevated in systemic inflammation and some cancers.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates IL-6's bioactivity.", "mechanism": "IL-6 is associated with cancer-related inflammation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation affects CRP's half-life and function.", "mechanism": "CRP is elevated in T2DM, reflecting chronic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12535657" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Glycosylation affects ABCA1 stability and trafficking, impacting cholesterol export.", "mechanism": "Altered expression of ABCA1 affects cholesterol transport, leading to bile supersaturation and cholesterol crystal formation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "causal", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Glycosylation modulates NPC1L1 membrane localization and function.", "mechanism": "Altered NPC1L1 expression increases hepatic cholesterol uptake, promoting bile cholesterol supersaturation and gallstone formation.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "causal", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Glycosylation may affect ALT secretion and stability.", "mechanism": "Elevated ALT is part of the hepatic steatosis index, which predicts increased gallstone risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Glycosylation may influence AST activity and serum levels.", "mechanism": "AST levels are included in the hepatic steatosis index, correlating with gallstone risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "Gallstones", "glycan_involvement": "Glycosylation is essential for GGT enzymatic activity.", "mechanism": "Elevated GGT is associated with liver dysfunction and increased gallstone risk.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation regulates ABCA1 function in hepatocytes.", "mechanism": "ABCA1 dysfunction impairs cholesterol efflux, contributing to hepatic lipid accumulation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "causal", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects NPC1L1 activity in liver cells.", "mechanism": "NPC1L1-mediated cholesterol uptake promotes hepatic steatosis.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "causal", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may modulate ALT release.", "mechanism": "ALT is a marker of hepatocellular injury and is elevated in NAFLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect AST stability.", "mechanism": "AST elevation reflects liver injury in NAFLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation is required for GGT activity.", "mechanism": "GGT is elevated in NAFLD and reflects oxidative stress and liver dysfunction.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12535658" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "P-gp is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Upregulation of P-gp reduces intestinal inflammation and permeability via the P-gp/eCB axis.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "ZO-1 is glycosylated, which may affect tight junction stability.", "mechanism": "Reduced ZO-1 expression is associated with increased intestinal permeability and IBD pathology.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Occludin glycosylation is important for tight junction assembly.", "mechanism": "Loss of occludin disrupts tight junctions, increasing permeability and promoting inflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Glycosylation required for P-gp stability and function.", "mechanism": "P-gp upregulation by isoorientin-modulated metabolites protects against colitis by reducing inflammation.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12537527" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "CB2 is glycosylated, which may influence receptor function.", "mechanism": "CB2 activation reduces inflammatory cytokine production and maintains barrier integrity.", "protein": "CB2", "relationship_type": "protective", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Glycosylation may stabilize ZO-1 at tight junctions.", "mechanism": "Restoration of ZO-1 expression by isoorientin-modulated metabolites correlates with improved barrier function.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Glycosylation is important for occludin's function in tight junctions.", "mechanism": "Occludin restoration reduces LPS-induced permeability and inflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "medium", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Glycosylation affects P-gp trafficking and function.", "mechanism": "Reduced P-gp expression may contribute to increased permeability and NEC pathogenesis.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12537527" }, { "confidence": "medium", "disease": "Celiac Disease", "glycan_involvement": "Glycosylation may modulate ZO-1 localization.", "mechanism": "Decreased ZO-1 expression is linked to barrier dysfunction in celiac disease.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation is necessary for occludin's barrier function.", "mechanism": "Reduced occludin expression is associated with increased gut permeability in diabetes.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12537527" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation affects stability and receptor interactions.", "mechanism": "Promotes clearance of amyloid-beta peptides, maintains neuronal and vascular integrity.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "protective/causal", "source_pmcid": "PMC12538646" }, { "confidence": "high", "disease": "Vascular dementia (VD)", "glycan_involvement": "N-glycosylation modulates lipid transport and vascular interactions.", "mechanism": "Supports neurovascular regulation and white matter integrity.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "protective", "source_pmcid": "PMC12538646" }, { "confidence": "high", "disease": "Parkinson's disease dementia (PDD)", "glycan_involvement": "N-glycosylation influences neuronal uptake and clearance.", "mechanism": "Reduces neurodegeneration and supports synaptic function.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "protective", "source_pmcid": "PMC12538646" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "Enhances microglial clearance of amyloid-beta and regulates neuroinflammation.", "protein": "Triggering receptor expressed on myeloid cells 2 (TREM2)", "relationship_type": "protective/causal", "source_pmcid": "PMC12538646" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation essential for trafficking and antigen presentation.", "mechanism": "Modulates MHC class II processing and immune response in neurons.", "protein": "CD74 molecule (CD74)", "relationship_type": "protective", "source_pmcid": "PMC12538646" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation modulates receptor function and immune interactions.", "mechanism": "Regulates immune signaling and may suppress neuroinflammation.", "protein": "Fc receptor-like 3 (FCRL3)", "relationship_type": "protective", "source_pmcid": "PMC12538646" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation affects immune cell interactions.", "mechanism": "Involved in adaptive immune response; higher levels increase AD risk.", "protein": "Butyrophilin subfamily 3 member A2 (BTN3A2)", "protein_enriched": { "function": "", "gene_name": "PRSS41", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q7RTY9" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12538646" }, { "confidence": "high", "disease": "Vascular dementia (VD)", "glycan_involvement": "Glycosylation modulates vascular and immune signaling.", "mechanism": "Promotes immune dysregulation and vascular injury.", "protein": "Butyrophilin subfamily 3 member A2 (BTN3A2)", "protein_enriched": { "function": "", "gene_name": "PRSS41", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q7RTY9" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12538646" }, { "confidence": "medium", "disease": "Vascular dementia (VD)", "glycan_involvement": "N-glycosylation critical for cell adhesion and axonal stability.", "mechanism": "Maintains myelinated axon integrity; higher levels linked to increased VD risk.", "protein": "Contactin-2 (CNTN2)", "protein_enriched": { "function": "In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal ", "gene_name": "CNTN2", "glycan_count": 6, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G31852PQ", "G41071NU", "G62765YT", "G81315DD", "G90659AW", "G39446WN" ], "uniprot_id": "Q02246" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12538646" }, { "confidence": "medium", "disease": "White matter hyperintensities (WMHs)", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "Pro-inflammatory mediator; higher levels linked to greater white matter injury.", "protein": "Granzyme A (GZMA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12538646" }, { "confidence": "medium", "disease": "Organ transplant rejection", "glycan_involvement": "OX40 is a glycoprotein; glycosylation affects ligand binding and immune signaling.", "mechanism": "OX40-specific antibodies deplete memory T cells, improving tolerance induction.", "protein": "OX40", "protein_enriched": { "function": "Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity", "gene_name": "TNFRSF4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43489" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "CD2 glycosylation modulates cell-cell adhesion and antibody binding.", "mechanism": "Anti-CD2 monoclonal antibodies (e.g., siplizumab) target memory T cells to facilitate tolerance.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "CD25 glycosylation influences receptor stability and IL-2 binding.", "mechanism": "IL-2 muteins with high affinity for CD25 selectively expand Tregs, promoting tolerance.", "protein": "CD25 (IL-2R\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "N-glycosylation critical for HLA folding and surface expression.", "mechanism": "Polymorphic HLA class I triggers adaptive immune response; silencing prevents rejection.", "protein": "HLA class I", "relationship_type": "causal", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "N-glycosylation required for antigen presentation.", "mechanism": "Polymorphic HLA class II activates T and B cells; silencing reduces immunogenicity.", "protein": "HLA class II", "relationship_type": "causal", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "Glycosylation modulates CD47-SIRP\u03b1 interaction.", "mechanism": "CD47 overexpression inhibits innate immune cell-mediated graft rejection.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "protective", "source_pmcid": "PMC12539449" }, { "confidence": "medium", "disease": "Placental inflammation", "glycan_involvement": "Glycosylation affects FasL stability and apoptotic signaling.", "mechanism": "FasL expression at the placental interface suppresses T cell responses, preventing inflammation.", "protein": "FasL", "relationship_type": "protective", "source_pmcid": "PMC12539449" }, { "confidence": "medium", "disease": "Organ transplant rejection", "glycan_involvement": "Glycosylation may affect IDO secretion and activity.", "mechanism": "IDO expression suppresses T cell responses, promoting tolerance.", "protein": "Indoleamine 2,3-dioxygenase (IDO)", "protein_enriched": { "function": "Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contrib", "gene_name": "IDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14902" }, "relationship_type": "protective", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "Glycosylation may regulate FOXP3 stability and function.", "mechanism": "FOXP3+ regulatory T cell infiltrates correlate with operational tolerance.", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12539449" }, { "confidence": "medium", "disease": "Placental inflammation", "glycan_involvement": "Glycosylation influences chemokine secretion and receptor interaction.", "mechanism": "Th1-skewed chemokine expression promotes inflammation resembling transplant rejection.", "protein": "CXCL9/10/11", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12539449" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Reduced antennary fucosylation, trigalactosylation, and monosialylation in MS compared to Ab-defined diseases.", "mechanism": "Altered N-glycan branching, galactosylation, sialylation, and fucosylation on IgG distinguish MS from Ab-defined diseases.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Secondary Progressive MS (SPMS)", "glycan_involvement": "Increased high mannose-content glycans and GlycA in SPMS.", "mechanism": "Elevated N-acetylglucosamine (GlycA) and high mannose glycans in plasma IgG associated with SPMS progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Aquaporin-4 antibody NMOSD (AQP4-Ab NMOSD)", "glycan_involvement": "Increased high branching, trigalactosylation, antennary fucosylation, and disialylation.", "mechanism": "Highly branched, complex N-glycans (antenna, sialylation, galactosylation, fucosylation) elevated in AQP4-Ab NMOSD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)", "glycan_involvement": "Elevated monosialylation and antennary fucosylation in MOGAD compared to MS.", "mechanism": "Distinct N-glycan traits (monosialylation, antennary fucosylation) differentiate MOGAD from MS and AQP4-Ab NMOSD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Altered galactosylation and sialylation reduce inflammation via Fc\u03b3RIIIa.", "mechanism": "N-glycan modifications on IgG modulate Fc\u03b3RIIIa-mediated inflammation and autoimmunity.", "protein": "Fc gamma receptor IIIa (Fc\u03b3RIIIa)", "relationship_type": "causal", "source_pmcid": "PMC12539935" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Increased galactosylation on plasma glycoproteins.", "mechanism": "Galactosylated N-glycans inhibit complement C5a, reducing inflammation.", "protein": "Complement component C5a", "protein_enriched": { "function": "Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling ", "gene_name": "C5", "glycan_count": 29, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G12580WI", "G06356OH", "G48414YA", "G04854VP", "G06247RL", "G08918WF", "G10486CT", "G25418HZ", "G26330YA", "G27058EU", "G27947YN", "G38663NM", "G40574BA", "G40926MX", "G45395BF", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G77669RF", "G84452RH", "G90659AW", "G92551JA", "G94470IW", "G95865ZB", "G42227JK", "G49108TO" ], "uniprot_id": "P01031" }, "relationship_type": "protective", "source_pmcid": "PMC12539935" }, { "confidence": "medium", "disease": "Secondary Progressive MS (SPMS)", "glycan_involvement": "Elevated mannose-rich glycans in SPMS.", "mechanism": "Mannose-rich N-glycans activate complement via mannose-binding lectin, linked to microglia-driven pathology in SPMS.", "protein": "Mannose-binding lectin", "relationship_type": "causal", "source_pmcid": "PMC12539935" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Decreased N-glycan branching triggers autoimmunity.", "mechanism": "Reduced N-glycan branching on APCs promotes B-cell mediated inflammation and demyelination.", "protein": "Antigen-presenting cell (APC) glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Relapsing-Remitting MS (RRMS)", "glycan_involvement": "Reduced AF, G3, and HB glycans in RRMS.", "mechanism": "Lower antennary fucosylation, trigalactosylation, and high branching N-glycans distinguish RRMS from AQP4-Ab NMOSD and MOGAD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Aquaporin-4 antibody NMOSD (AQP4-Ab NMOSD)", "glycan_involvement": "Increased S2, nFS2, FG2, and FGS/(FG+FGS) in AQP4-Ab NMOSD.", "mechanism": "Elevated disialylation and fucosylation traits distinguish AQP4-Ab NMOSD from MOGAD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12539935" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "OmpA is a glycoprotein receptor; accessibility modulated by LPS and amylovoran.", "mechanism": "OmpA serves as a receptor for E. amylovora phages, facilitating phage infection and bacterial lysis.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "Amylovoran (EPS) is attached to LPS, possibly via N-acetyl-galactosamine linkage.", "mechanism": "LPS, tightly associated with amylovoran, is recognized by phages as a receptor, enabling infection.", "protein": "LPS (decorated with amylovoran)", "relationship_type": "causal", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "Amylovoran is a galactose-rich EPS, possibly N-acetyl-galactosamine modified.", "mechanism": "Amylovoran is essential for E. amylovora virulence and acts as a phage receptor when attached to LPS.", "protein": "Amylovoran", "relationship_type": "causal", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Streptomycin-resistant fire blight", "glycan_involvement": "OmpA accessibility is influenced by LPS/EPS glycan structure.", "mechanism": "Phage-carrier systems exploit OmpA as a receptor to target and lyse resistant E. amylovora.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "O-antigen and core oligosaccharide glycan modifications modulate receptor function.", "mechanism": "LPS structure affects phage susceptibility and bacterial virulence.", "protein": "LPS (E. amylovora)", "relationship_type": "causal", "source_pmcid": "PMC12540986" }, { "confidence": "medium", "disease": "Fire blight", "glycan_involvement": "O-glycosylation with N-acetyl-galactosamine.", "mechanism": "Flagellin O-glycosylation mimics LPS glycan epitopes, potentially confounding phage receptor identification.", "protein": "Flagellin (FliC)", "protein_enriched": { "function": "Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella", "gene_name": "fliC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5XPM8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12540986" }, { "confidence": "medium", "disease": "Fire blight", "glycan_involvement": "Glycan environment modulates inhibitor access.", "mechanism": "Blocking OmpA with inhibitors (e.g., AOA-2) prevents phage infection, protecting bacteria.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "Absence of amylovoran decoration.", "mechanism": "LPS lacking amylovoran does not trigger phage DNA ejection, protecting P. agglomerans from phage infection.", "protein": "LPS (P. agglomerans)", "relationship_type": "protective", "source_pmcid": "PMC12540986" }, { "confidence": "medium", "disease": "Fire blight", "glycan_involvement": "Involved in N-acetyl-galactosamine transfer for glycan linkage.", "mechanism": "Mutation in EAMY_2231 alters amylovoran-LPS linkage, conferring phage resistance.", "protein": "EAMY_2231 (putative glycosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12540986" }, { "confidence": "high", "disease": "Fire blight", "glycan_involvement": "Glycan modifications affect OmpA exposure and phage binding.", "mechanism": "Phage-carrier systems use OmpA as a universal receptor for targeting both E. amylovora and P. agglomerans.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12540986" }, { "confidence": "medium", "disease": "Congenital hyperinsulinism", "glycan_involvement": "No direct glycosylation mechanism described; possible indirect effects on glycoprotein processing.", "mechanism": "Loss-of-function variants in CARS1 impair cysteine persulfide synthesis, affecting CaMKII regulation of beta cell KATP channels, leading to dysregulated insulin secretion.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "high", "disease": "Microcephaly, Developmental Delay, and Brittle Hair Syndrome (OMIM 618891)", "glycan_involvement": "Suspected due to abnormal glycosylation studies, but not confirmed.", "mechanism": "Compound heterozygous or homozygous CARS1 variants cause multisystem syndrome with neurodevelopmental and hair/nail abnormalities.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Not directly described.", "mechanism": "Some patients with CARS1 variants develop early-onset type 2 diabetes, possibly due to beta cell dysfunction.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "Not directly described.", "mechanism": "CARS1 variants associated with hypoglycemia, sometimes due to hyperinsulinism.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "high", "disease": "Trichorrhexis nodosa", "glycan_involvement": "Not directly described.", "mechanism": "CARS1 variants cause brittle hair with trichorrhexis nodosa observed on microscopy.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Not described.", "mechanism": "De novo CARS1 variant (p.Asn348Ser) reported in a patient with autism.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "low", "disease": "Parkinsonism-spinocerebellar ataxia", "glycan_involvement": "Not described.", "mechanism": "Heterozygous CARS1 variant (p.Glu795Val) segregates with Parkinsonism-spinocerebellar ataxia in a family.", "protein": "Cysteinyl-tRNA synthetase 1 (CARS1)", "protein_enriched": { "function": "Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: ", "gene_name": "LARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2J5" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "low", "disease": "Congenital hyperinsulinism", "glycan_involvement": "Not described.", "mechanism": "Homozygous YARS1 variant reported in a patient with hyperinsulinism.", "protein": "Tyrosyl-tRNA synthetase (YARS1)", "protein_enriched": { "function": "Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA", "gene_name": "YARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54577" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "low", "disease": "Hypoglycemia", "glycan_involvement": "Not described.", "mechanism": "Hypoglycemia reported in patients with homozygous YARS1 variants.", "protein": "Tyrosyl-tRNA synthetase (YARS1)", "protein_enriched": { "function": "Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA", "gene_name": "YARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54577" }, "relationship_type": "causal", "source_pmcid": "PMC12542199" }, { "confidence": "high", "disease": "Congenital hyperinsulinism", "glycan_involvement": "Insulin is a glycoprotein; glycosylation not discussed in this context.", "mechanism": "Elevated insulin during hypoglycemia is diagnostic for hyperinsulinism.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542199" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "K17 is stabilized by FUT11-mediated fucosylation, which enhances its K63-linked ubiquitination and prevents degradation.", "mechanism": "Overexpressed K17 drives keratinocyte hyperproliferation and inflammation via immune cell recruitment and cytokine signaling.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "causal", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "FUT11 catalyzes \u03b1-1,3-fucosylation of K17, facilitating its K63-linked ubiquitination.", "mechanism": "FUT11 is upregulated in psoriatic keratinocytes and mediates fucosylation of K17, sustaining its stability and promoting disease progression.", "protein": "Fucosyltransferase 11 (FUT11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Fucosylation status of K17 reflects disease activity.", "mechanism": "K17 is specifically overexpressed in psoriatic keratinocytes and correlates with disease severity.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Directly mediates fucosylation of K17.", "mechanism": "FUT11 upregulation leads to increased fucosylation and stabilization of K17, driving keratinocyte proliferation and inflammation.", "protein": "Fucosyltransferase 11 (FUT11)", "relationship_type": "causal", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Loss of fucosylation leads to reduced K17 stability and increased degradation.", "mechanism": "Destabilization or degradation of K17 (by inhibiting fucosylation or FUT11) reduces keratinocyte proliferation and inflammation.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12542314" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Reflects increased fucosylation activity in disease.", "mechanism": "FUT11 expression is elevated in psoriatic lesions and correlates with keratinocyte proliferation.", "protein": "Fucosyltransferase 11 (FUT11)", "relationship_type": "biomarker", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Fucosylation enhances K17's stability and function in immune signaling.", "mechanism": "K17 acts as an immunoregulatory hub, amplifying the K17/T-cell/cytokine feedback loop in psoriasis.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "causal", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Blocks fucosylation of K17, disrupting its stabilization.", "mechanism": "Inhibition or silencing of FUT11 reduces K17 stability, keratinocyte proliferation, and inflammation, ameliorating psoriasis symptoms.", "protein": "Fucosyltransferase 11 (FUT11)", "relationship_type": "protective (when inhibited)", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "FUT11-mediated fucosylation is required for K17-Trim21 interaction and subsequent ubiquitination.", "mechanism": "Fucosylated K17 interacts with E3 ligase Trim21, promoting K63-linked ubiquitination and protein stabilization.", "protein": "Keratin 17 (K17)", "protein_enriched": { "function": "Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair ", "gene_name": "KRT17", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04695" }, "relationship_type": "causal", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Prevents fucosylation of K17, leading to its degradation.", "mechanism": "Pharmacological inhibition of fucosylation (e.g., with 2-FF) or FUT11 silencing reduces psoriatic inflammation and keratinocyte proliferation.", "protein": "Fucosyltransferase 11 (FUT11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12542314" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Binds exposed glycans on damaged lysosomal membranes.", "mechanism": "Upregulated and recruited to damaged lysosomes, marking lysosomal membrane permeabilization (LMP) in DMD muscle fibers.", "protein": "Galectin-3 (LGALS3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentia", "gene_name": "LGALS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17931" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Heavily glycosylated; glycosylation maintains lysosomal membrane integrity.", "mechanism": "Increased expression and altered morphology indicate lysosomal stress and dysfunction in DMD muscle.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects lysosomal targeting and stability.", "mechanism": "Upregulated and leaks into cytoplasm due to LMP, contributing to tissue damage and inflammation.", "protein": "Cathepsin B (CTSB)", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins (By similarity). Cleaves matrix extracellular phosphoglycoprotein MEPE (By similarity). Involved i", "gene_name": "Ctsb", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G14260UH", "G48584BU", "G57776ZU", "G64527OM", "G28622IK", "G41247ZX" ], "uniprot_id": "P10605" }, "relationship_type": "causal", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation required for lysosomal localization.", "mechanism": "Upregulated and mislocalized in DMD muscle, promoting proteolysis and cell death.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "causal", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Regulates expression of lysosomal glycoproteins.", "mechanism": "Activated in response to lysosomal stress, drives lysosomal biogenesis but incompletely corrects dysfunction.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation modulates autophagy receptor function.", "mechanism": "Accumulation indicates impaired autophagic flux and lysosomal dysfunction.", "protein": "SQSTM1 (p62)", "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Indirect; interacts with glycoprotein cargo.", "mechanism": "Altered LC3B ratios reflect defective autophagosome-lysosome fusion in DMD muscle.", "protein": "LC3B (MAP1LC3B)", "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "May interact with glycosylated lysosomal proteins during repair.", "mechanism": "Upregulated and recruited to lysosomes, indicating activation of ESCRT-mediated lysosomal repair.", "protein": "ALIX (PDCD6IP)", "protein_enriched": { "function": "Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in co", "gene_name": "PDCD6IP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G39446WN" ], "uniprot_id": "Q8WUM4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type R5 (LGMDR5)", "glycan_involvement": "Glycosylation essential for membrane localization and complex stability.", "mechanism": "Loss leads to DAGC disruption and lysosomal dysfunction; gene therapy restores lysosomal integrity.", "protein": "\u03b3-sarcoglycan (SGCG)", "relationship_type": "causal", "source_pmcid": "PMC12542950" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophy type R5 (LGMDR5)", "glycan_involvement": "Binds exposed glycans on damaged lysosomal membranes.", "mechanism": "Upregulated and recruited to lysosomes, marking LMP in LGMDR5 muscle fibers.", "protein": "Galectin-3 (LGALS3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentia", "gene_name": "LGALS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17931" }, "relationship_type": "biomarker", "source_pmcid": "PMC12542950" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Likely requires glycosylation for secretion and function (as a secreted protein).", "mechanism": "Improves insulin sensitivity and lowers blood glucose in db/db mice.", "protein": "JUV-161", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543550" }, { "confidence": "high", "disease": "Sarcopenia (diabetes-related myopathy)", "glycan_involvement": "Glycosylation may affect stability and muscle targeting.", "mechanism": "Promotes lean muscle mass and increases muscle weights in diabetic mice.", "protein": "JUV-161", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543550" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Secreted glycoprotein function may depend on glycan structure.", "mechanism": "Improves metabolic parameters associated with obesity (insulin resistance, muscle loss).", "protein": "JUV-161", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543550" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation may modulate tissue distribution and efficacy.", "mechanism": "Reduces serum AST, indicating protection against liver damage.", "protein": "JUV-161", "relationship_type": "protective", "source_pmcid": "PMC12543550" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Glycosylation may affect renal clearance and bioactivity.", "mechanism": "Reduces serum creatinine, indicating protection against kidney damage.", "protein": "JUV-161", "relationship_type": "protective", "source_pmcid": "PMC12543550" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "N-glycosylation affects HSA stability and half-life.", "mechanism": "Used as vehicle control; no therapeutic effect.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "control", "source_pmcid": "PMC12543550" }, { "confidence": "high", "disease": "Severe obesity", "glycan_involvement": "TSP1 is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Circulating TSP1 levels are reduced in severe obesity, especially under hypoxic adipose conditions.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may modulate TSP1's interaction with metabolic pathways.", "mechanism": "TSP1 levels correlate with HbA1c and insulin resistance indices.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Adipose tissue dysfunction", "glycan_involvement": "Glycosylation may influence TSP1's secretion from adipocytes.", "mechanism": "TSP1 is linked to adipose tissue dysfunction; hypoxia in adipose tissue suppresses TSP1 expression.", "protein": "Thrombospondin-1", "relationship_type": "causal", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Cardiometabolic risk", "glycan_involvement": "Glycosylation status may affect TSP1's biomarker utility.", "mechanism": "TSP1 is proposed as a biomarker for cardiometabolic risk in obesity.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "low", "disease": "Vascular dysfunction", "glycan_involvement": "Glycosylation may regulate TSP1's vascular effects.", "mechanism": "Reduced TSP1 in severe obesity may be a compensatory response to mitigate vascular dysfunction.", "protein": "Thrombospondin-1", "relationship_type": "protective", "source_pmcid": "PMC12543555" }, { "confidence": "high", "disease": "Severe obesity", "glycan_involvement": "ET1 is a glycopeptide; glycosylation may affect its stability and receptor binding.", "mechanism": "Circulating ET1 levels are reduced in severe obesity.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Cardiometabolic risk", "glycan_involvement": "Glycosylation may modulate ET1's bioactivity.", "mechanism": "ET1 levels correlate with liver enzymes and triglycerides, reflecting cardiometabolic risk.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Inflammation (in obesity)", "glycan_involvement": "Glycosylation may influence TSP1's immune interactions.", "mechanism": "TSP1 correlates with white blood cell count and platelet count, indicating involvement in inflammatory pathways.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Thrombotic risk (in obesity)", "glycan_involvement": "Glycosylation may affect TSP1's interaction with platelets.", "mechanism": "TSP1-to-platelet ratio is decreased in severe obesity, reflecting altered platelet activation.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12543555" }, { "confidence": "medium", "disease": "Hypoxia-induced adipose dysfunction", "glycan_involvement": "Glycosylation may regulate TSP1's secretion under hypoxic conditions.", "mechanism": "Hypoxia in adipose tissue reduces TSP1 transcription and secretion.", "protein": "Thrombospondin-1", "relationship_type": "causal", "source_pmcid": "PMC12543555" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated AST levels are associated with T2DM and reflect hepatic dysfunction.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence secretion and activity.", "mechanism": "Elevated ALT levels are linked to T2DM, indicating liver involvement in metabolic dysregulation.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GGT is a glycoprotein; glycosylation impacts its serum half-life.", "mechanism": "Increased GGT is observed in T2DM, reflecting oxidative stress and hepatic steatosis.", "protein": "Gamma-Glutamyl Transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation may modulate AST release during liver injury.", "mechanism": "Elevated AST is associated with hepatic steatosis in T2DM patients.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation may affect ALT's stability in circulation.", "mechanism": "ALT elevation signals liver fat accumulation and damage in T2DM.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation influences GGT's serum levels.", "mechanism": "GGT elevation is linked to hepatic steatosis and metabolic dysfunction.", "protein": "Gamma-Glutamyl Transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "low", "disease": "Cardiovascular complications", "glycan_involvement": "Glycosylation may affect AST's diagnostic value.", "mechanism": "Elevated AST in T2DM patients is associated with increased cardiovascular risk.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "low", "disease": "Cardiovascular complications", "glycan_involvement": "Glycosylation may modulate ALT's serum detection.", "mechanism": "ALT elevation in T2DM is linked to higher cardiovascular risk.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "low", "disease": "Cardiovascular complications", "glycan_involvement": "Glycosylation impacts GGT's function and clearance.", "mechanism": "GGT elevation is associated with increased cardiovascular complications in T2DM.", "protein": "Gamma-Glutamyl Transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12543577" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "GLP-1R is a glycoprotein; glycosylation may affect receptor function and ligand binding.", "mechanism": "Excessive activation of GLP-1R on pancreatic exocrine and islet cells may lead to ductal obstruction and inflammation.", "protein": "GLP-1R", "relationship_type": "causal", "source_pmcid": "PMC12543584" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "Semaglutide is a glycopeptide; glycosylation enhances stability and receptor interaction.", "mechanism": "Semaglutide (GLP-1 analog) triggers excessive GLP-1R activation, leading to pancreatitis.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12543584" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation of GLP-1R may modulate receptor activity.", "mechanism": "GLP-1R agonists improve glycemic control.", "protein": "GLP-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543584" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation increases drug half-life and efficacy.", "mechanism": "Semaglutide acts as a GLP-1R agonist to lower blood glucose.", "protein": "Semaglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12543584" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation improves pharmacokinetics.", "mechanism": "Semaglutide suppresses appetite via GLP-1R activation.", "protein": "Semaglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12543584" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSH indicates thyroid hormone deficiency.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "high", "disease": "Myxedema coma", "glycan_involvement": "Glycosylation modulates TSH bioactivity and half-life.", "mechanism": "Profoundly elevated TSH is diagnostic for severe hypothyroidism leading to myxedema coma.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "TBG is N-glycosylated, which influences its binding affinity and serum half-life.", "mechanism": "TBG binds and transports thyroid hormones; altered levels affect hormone availability.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Elevated CK reflects muscle breakdown in rhabdomyolysis.", "protein": "Creatine Kinase (CK)", "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Myoglobin released from damaged muscle can cause renal injury.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Acute compartment syndrome", "glycan_involvement": "TSH glycosylation may affect its bioactivity and downstream effects on tissue metabolism.", "mechanism": "Severe hypothyroidism (high TSH) leads to tissue edema, predisposing to compartment syndrome.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "TSH glycosylation modulates hormone signaling.", "mechanism": "Severe hypothyroidism impairs muscle metabolism, increasing risk for rhabdomyolysis.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Myxedema coma", "glycan_involvement": "N-glycosylation of TBG affects its serum stability.", "mechanism": "Altered TBG levels can exacerbate hormone deficiency in myxedema coma.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "TSH glycosylation may indirectly affect renal outcomes via hormone signaling.", "mechanism": "Severe hypothyroidism (high TSH) can lead to rhabdomyolysis and myoglobinuria, causing renal injury.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Elevated AST reflects muscle and liver injury in rhabdomyolysis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543591" }, { "confidence": "medium", "disease": "Type II Amiodarone-induced Thyrotoxicosis (AIT)", "glycan_involvement": "TSI is an autoantibody glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSI levels indicate autoimmune thyroid stimulation, contributing to thyrotoxicosis.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC12543600" }, { "confidence": "high", "disease": "Type II Amiodarone-induced Thyrotoxicosis (AIT)", "glycan_involvement": "T4 is transported by glycoprotein carriers; glycosylation affects hormone transport.", "mechanism": "Elevated free T4 is a hallmark of thyrotoxicosis.", "protein": "Thyroid Hormone (T4)", "relationship_type": "biomarker", "source_pmcid": "PMC12543600" }, { "confidence": "high", "disease": "Type II Amiodarone-induced Thyrotoxicosis (AIT)", "glycan_involvement": "T3 is transported by glycoprotein carriers; glycosylation affects hormone transport.", "mechanism": "Elevated T3 is a marker of thyrotoxicosis.", "protein": "Thyroid Hormone (T3)", "relationship_type": "biomarker", "source_pmcid": "PMC12543600" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TRAb glycosylation affects antibody stability and immune recognition", "mechanism": "TRAb stimulates TSH receptor, causing hyperthyroidism", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "high", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation modulates TRAb function and clearance", "mechanism": "TRAb drives excessive thyroid hormone production", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "Albumin glycosylation influences hormone binding capacity", "mechanism": "Albumin used as replacement fluid in TPE to bind and remove thyroid hormones", "protein": "Albumin (ALB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "N-glycosylation of TBG modulates hormone affinity", "mechanism": "TBG binds circulating thyroid hormones, affecting their bioavailability", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Graves' disease", "glycan_involvement": "Glycosylation affects TPO antigenicity", "mechanism": "TPO is a target of autoantibodies in Graves' disease", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "N-glycosylation critical for TG folding and secretion", "mechanism": "TG levels reflect thyroid hormone synthesis and release", "protein": "Thyroglobulin (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation may affect TRAb pathogenicity", "mechanism": "High TRAb levels precipitate acute thyroid hormone excess", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC12543608" }, { "confidence": "medium", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation may modulate albumin's hormone binding", "mechanism": "Albumin in TPE facilitates rapid reduction of circulating thyroid hormones", "protein": "Albumin (ALB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12543608" }, { "confidence": "low", "disease": "Amiodarone-induced thyrotoxicosis", "glycan_involvement": "Altered glycosylation may affect TBG function in disease", "mechanism": "TBG levels influence thyroid hormone distribution in drug-induced thyrotoxicosis", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "low", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation impacts TPO immunogenicity", "mechanism": "TPO autoantibodies may be present in thyrotoxicosis", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC12543608" }, { "confidence": "high", "disease": "Cushing's disease", "glycan_involvement": "ACTH is glycosylated, which affects its stability and receptor binding.", "mechanism": "Elevated ACTH indicates ACTH-dependent hypercortisolism, a hallmark of Cushing's disease.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC12543813" }, { "confidence": "medium", "disease": "Primary hyperaldosteronism", "glycan_involvement": "Glycosylation modulates ACTH bioactivity.", "mechanism": "ACTH levels help differentiate between ACTH-dependent and independent causes of adrenal hormone excess.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC12543813" }, { "confidence": "medium", "disease": "Cushing's disease", "glycan_involvement": "CBG glycosylation affects cortisol binding affinity.", "mechanism": "CBG binds cortisol; altered levels reflect cortisol excess in Cushing's disease.", "protein": "Cortisol-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12543813" }, { "confidence": "medium", "disease": "Primary hyperaldosteronism", "glycan_involvement": "MC2R glycosylation is essential for receptor trafficking and function.", "mechanism": "MC2R mediates ACTH signaling in adrenal cortex, influencing aldosterone production.", "protein": "Adrenocorticotropic hormone receptor (MC2R)", "protein_enriched": { "function": "Hormone receptor primarily expressed in adrenal cortex that plays a key role in regulating adrenocortical function (PubMed:36588120). Upon corticotropin (ACTH) binding, facilitates the release of adre", "gene_name": "MC2R", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q01718" }, "relationship_type": "causal", "source_pmcid": "PMC12543813" }, { "confidence": "low", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation affects ACTH half-life and activity.", "mechanism": "Elevated ACTH may indicate underlying endocrine disorder contributing to hypokalemia-induced rhabdomyolysis.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC12543813" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation regulates CBG stability and cortisol transport.", "mechanism": "CBG modulates free cortisol levels, which can contribute to hypertension.", "protein": "Cortisol-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12543813" }, { "confidence": "high", "disease": "Leptospirosis", "glycan_involvement": "IgM is a heavily N-glycosylated antibody; glycosylation affects its stability and immune function.", "mechanism": "Leptospirosis IgM is used as a serological marker for acute infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544083" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used to diagnose and monitor diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544083" }, { "confidence": "medium", "disease": "Direct Hyperbilirubinemia", "glycan_involvement": "Alkaline phosphatase is N-glycosylated, which affects its secretion and stability.", "mechanism": "Elevated alkaline phosphatase indicates cholestasis or hepatobiliary dysfunction.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544083" }, { "confidence": "medium", "disease": "Direct Hyperbilirubinemia", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its serum half-life.", "mechanism": "Elevated AST is a marker of hepatocellular injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544083" }, { "confidence": "medium", "disease": "Direct Hyperbilirubinemia", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its function.", "mechanism": "Elevated ALT is a marker of hepatocellular injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544083" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Includes glycoproteins AST and ALT as components.", "mechanism": "FIB-4 is used as a non-invasive biomarker to estimate liver fibrosis in MASLD.", "protein": "Fibrosis-4 index (FIB-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated AST levels are associated with MASLD and used in diagnosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated ALT levels are associated with MASLD and used in diagnosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Includes glycoproteins AST and ALT as components.", "mechanism": "FIB-4 is used to estimate risk of advanced fibrosis in MASH.", "protein": "Fibrosis-4 index (FIB-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "T2D", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects glycemic control in T2D.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated AST is associated with MASH diagnosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated ALT is associated with MASH diagnosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Includes glycoproteins AST and ALT as components.", "mechanism": "FIB-4 is used to estimate risk of cirrhosis in MASLD/MASH.", "protein": "Fibrosis-4 index (FIB-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated AST is associated with advanced liver disease including cirrhosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect serum levels.", "mechanism": "Elevated ALT is associated with advanced liver disease including cirrhosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544209" }, { "confidence": "high", "disease": "Type 1 Diabetes Recurrence (T1DR)", "glycan_involvement": "GAD65 is glycosylated; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Elevated anti-GAD65 antibodies indicate autoimmune attack on pancreatic beta cells in the graft.", "protein": "Glutamic Acid Decarboxylase 65 (GAD65)", "protein_enriched": { "function": "Catalyzes the production of GABA", "gene_name": "GAD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05329" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Insulin is glycosylated; glycosylation can influence immunogenicity.", "mechanism": "Insulin autoantibodies are markers of autoimmune beta cell destruction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "IA-2 is glycosylated; glycan structures may modulate immune recognition.", "mechanism": "IA-2 autoantibodies are associated with autoimmune diabetes.", "protein": "IA-2 (PTPRN)", "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "ZnT8 is glycosylated; glycosylation may affect antigen presentation.", "mechanism": "ZnT8 autoantibodies are linked to beta cell autoimmunity.", "protein": "Zinc Transporter 8 (ZnT8)", "protein_enriched": { "function": "Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion", "gene_name": "SLC30A8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IWU4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "high", "disease": "Pancreatic Graft Dysfunction", "glycan_involvement": "Glycosylation may influence GAD65's immunogenicity and susceptibility to autoimmunity.", "mechanism": "Autoimmunity against GAD65 leads to beta cell destruction and graft failure.", "protein": "Glutamic Acid Decarboxylase 65 (GAD65)", "protein_enriched": { "function": "Catalyzes the production of GABA", "gene_name": "GAD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05329" }, "relationship_type": "causal", "source_pmcid": "PMC12544426" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation can modulate antibody binding.", "mechanism": "Anti-GAD65 antibodies are diagnostic for T1DM.", "protein": "Glutamic Acid Decarboxylase 65 (GAD65)", "protein_enriched": { "function": "Catalyzes the production of GABA", "gene_name": "GAD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05329" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Pancreatic Graft Dysfunction", "glycan_involvement": "Insulin glycosylation may affect secretion and immune recognition.", "mechanism": "Loss of insulin production indicates graft failure.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Pancreatic Graft Dysfunction", "glycan_involvement": "Glycosylation may affect IA-2 antigenicity.", "mechanism": "IA-2 autoantibodies may signal ongoing autoimmunity in the graft.", "protein": "IA-2 (PTPRN)", "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Pancreatic Graft Dysfunction", "glycan_involvement": "Glycosylation may modulate ZnT8 immune response.", "mechanism": "ZnT8 autoantibodies may indicate beta cell autoimmunity in the graft.", "protein": "Zinc Transporter 8 (ZnT8)", "protein_enriched": { "function": "Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion", "gene_name": "SLC30A8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IWU4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544426" }, { "confidence": "medium", "disease": "Type 1 Diabetes Recurrence (T1DR)", "glycan_involvement": "Glycosylation could be leveraged to alter immunogenicity for therapy.", "mechanism": "Targeting GAD65 autoimmunity may help prevent graft dysfunction.", "protein": "Glutamic Acid Decarboxylase 65 (GAD65)", "protein_enriched": { "function": "Catalyzes the production of GABA", "gene_name": "GAD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05329" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544426" }, { "confidence": "high", "disease": "Cholestatic Jaundice", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated ALP indicates impaired bile flow due to cholestasis.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Cholestatic Jaundice", "glycan_involvement": "Glycosylation is essential for BSEP trafficking and function.", "mechanism": "PTU-induced oxidative stress and immune-mediated injury may impair glycoprotein transporters, leading to cholestasis.", "protein": "Bilirubin Transporters (BSEP)", "relationship_type": "causal", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "IgG glycosylation modulates immune activity and inflammation.", "mechanism": "Elevated IgG is a marker of autoimmune liver injury.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "ANA are glycoproteins; glycosylation may affect antigenicity.", "mechanism": "Elevated ANA suggests autoimmune liver involvement.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "ASMA glycosylation may influence immune recognition.", "mechanism": "Elevated ASMA is associated with autoimmune hepatitis.", "protein": "Anti-Smooth Muscle Antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "AMA glycosylation affects immune response.", "mechanism": "Elevated AMA is a marker for autoimmune liver disease.", "protein": "Anti-Mitochondrial Antibody (AMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "high", "disease": "PTU-Induced Hepatotoxicity", "glycan_involvement": "Glycosylation impacts ALP serum levels.", "mechanism": "ALP elevation signals cholestatic pattern of PTU-induced liver injury.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "PTU-Induced Hepatotoxicity", "glycan_involvement": "Glycosylation required for transporter function.", "mechanism": "PTU may impair glycoprotein transporters, causing cholestasis.", "protein": "Bilirubin Transporters (BSEP)", "relationship_type": "causal", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "PTU-Induced Hepatotoxicity", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "Elevated IgG may reflect immune activation in PTU-induced injury.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "low", "disease": "Graves' Disease", "glycan_involvement": "Glycosylation affects ALP activity.", "mechanism": "ALP may be elevated in Graves' disease with liver involvement.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12544469" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated AST levels are associated with increased liver fibrosis as measured by noninvasive tests.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence its activity and detection.", "mechanism": "ALT levels are used in AST/ALT ratio and NITs to predict fibrosis.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate interactions and may be altered in liver disease.", "mechanism": "Platelet count is used in FIB-4 and APRI scores to assess fibrosis risk.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect AST clearance and serum levels.", "mechanism": "AST levels are part of NITs for MASLD diagnosis and staging.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may impact ALT function and measurement.", "mechanism": "ALT is included in NITs for MASLD assessment.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Platelet glycoproteins may be altered in MASLD.", "mechanism": "Platelet count is a component of FIB-4 and APRI for MASLD risk stratification.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC12544479" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TRAb are glycosylated immunoglobulins; glycosylation affects antibody stability and receptor binding.", "mechanism": "TRAb binds to TSH receptor, stimulating thyroid hormone production and causing hyperthyroidism.", "protein": "TSH-receptor antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC12544504" }, { "confidence": "medium", "disease": "Acute Liver Injury (transaminitis)", "glycan_involvement": "Glycosylation of TRAb may modulate immune effector functions and hepatocyte targeting.", "mechanism": "TRAb-mediated immune activation may cause inflammatory injury to hepatocytes in Graves' Disease.", "protein": "TSH-receptor antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC12544504" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect its stability and release.", "mechanism": "GPNMB is upregulated in LAM core cells and macrophages; serum levels are high in LAM patients and reduced with mTOR inhibition.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12544566" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may regulate GPNMB cleavage and function.", "mechanism": "Down-regulation of GPNMB slows TSC2-null tumor growth and metastasis in models.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544566" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence GPNMB's cell surface expression and cleavage.", "mechanism": "GPNMB modulates cell proliferation, migration, and invasion in TSC2-null cells.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "causal", "source_pmcid": "PMC12544566" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect GPNMB's role in tumor progression.", "mechanism": "High GPNMB expression is associated with poor prognosis.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12544566" }, { "confidence": "medium", "disease": "Triple negative breast cancer", "glycan_involvement": "Glycosylation may affect GPNMB's role in tumor progression.", "mechanism": "High GPNMB expression is associated with poor prognosis.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12544566" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation due to impaired mannose metabolism.", "mechanism": "PMM2 deficiency impairs N-glycosylation of proteins, leading to multisystem dysfunction.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12544643" }, { "confidence": "medium", "disease": "Dandy Walker Malformation (DWM)", "glycan_involvement": "Abnormal N-glycosylation may disrupt brain development.", "mechanism": "PMM2-CDG may contribute to DWM, but causality is unclear due to limited cases.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "possible causal", "source_pmcid": "PMC12544643" }, { "confidence": "high", "disease": "Hypoglycemia", "glycan_involvement": "Impaired glycosylation affects hormone regulation.", "mechanism": "PMM2-CDG can cause persistent hypoglycemia, possibly via endocrine dysfunction.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12544643" }, { "confidence": "high", "disease": "Cerebellar atrophy", "glycan_involvement": "Defective N-glycosylation affects neuronal development.", "mechanism": "PMM2-CDG frequently leads to cerebellar atrophy and ataxia.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12544643" }, { "confidence": "medium", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Abnormal glycosylation of coagulation factors.", "mechanism": "PMM2-CDG patients have increased risk of VTE.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "associated", "source_pmcid": "PMC12544643" }, { "confidence": "medium", "disease": "Primary ovarian failure", "glycan_involvement": "Disrupted glycosylation of gonadotropins/receptors.", "mechanism": "PMM2-CDG can involve endocrine organs, leading to ovarian failure.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "associated", "source_pmcid": "PMC12544643" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Altered N-glycosylation pattern detected in serum.", "mechanism": "Carbohydrate-deficient transferrin is a diagnostic marker for PMM2-CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544643" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2-glycoprotein I are diagnostic for APS and mediate thrombosis.", "protein": "Beta-2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12544760" }, { "confidence": "high", "disease": "Acute Limb Ischemia (ALI)", "glycan_involvement": "Glycosylation modulates immune recognition and thrombogenicity.", "mechanism": "APS-related autoantibodies promote thrombus formation, leading to ALI.", "protein": "Beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12544760" }, { "confidence": "medium", "disease": "Recurrent Pregnancy Loss", "glycan_involvement": "Glycosylation influences placental binding and immune response.", "mechanism": "APS autoantibodies against beta-2-glycoprotein I disrupt placental function.", "protein": "Beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12544760" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation may affect epitope exposure.", "mechanism": "Antibodies against cardiolipin-binding glycoproteins are diagnostic for APS.", "protein": "Cardiolipin-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12544760" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Indirect; glycoprotein antigens are targeted by LA.", "mechanism": "Presence of lupus anticoagulant is a diagnostic criterion for APS.", "protein": "Lupus anticoagulant (LA)", "relationship_type": "biomarker", "source_pmcid": "PMC12544760" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Hyperglycemia may alter glycosylation patterns, affecting immune recognition.", "mechanism": "DM exacerbates vascular damage and hypercoagulability, increasing risk of APS-related events.", "protein": "Beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12544760" }, { "confidence": "medium", "disease": "Peripheral Arterial Disease (PAD)", "glycan_involvement": "Glycosylation modulates vascular interactions.", "mechanism": "APS autoantibodies promote atherothrombosis in PAD.", "protein": "Beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12544760" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation affects AST stability and secretion.", "mechanism": "Elevated AST indicates liver cell injury in hepatic steatosis.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "N-glycosylation modulates ALT serum levels.", "mechanism": "ALT elevation reflects hepatocellular damage due to alcohol toxicity.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation regulates leukocyte adhesion and migration.", "mechanism": "Leukocytosis is a marker of systemic inflammation in sepsis.", "protein": "Leukocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Shock", "glycan_involvement": "N-glycosylation influences albumin half-life and function.", "mechanism": "Low albumin is common in shock due to capillary leak and liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation is essential for receptor function.", "mechanism": "Insulin receptor signaling is impaired in T2DM.", "protein": "Insulin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation affects SGLT2 localization and activity.", "mechanism": "SGLT2 inhibition lowers glucose in T2DM.", "protein": "Empagliflozin target (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Metformin-associated lactic acidosis (MALA)", "glycan_involvement": "N-glycosylation modulates OCT1 trafficking.", "mechanism": "OCT1 mediates metformin uptake; impaired function increases toxicity risk.", "protein": "Metformin transporter (OCT1)", "relationship_type": "causal", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Metformin-associated lactic acidosis (MALA)", "glycan_involvement": "O-glycosylation may affect LDH activity.", "mechanism": "Elevated LDH reflects increased anaerobic metabolism in MALA.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "medium", "disease": "Shock", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Vasopressors act via glycosylated vasopressin receptors to restore blood pressure.", "protein": "Vasopressin receptor", "protein_enriched": { "function": "Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption", "gene_name": "AVPR2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30518" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544778" }, { "confidence": "low", "disease": "Pulmonary edema/ground glass opacities", "glycan_involvement": "Glycosylation modulates surfactant function.", "mechanism": "Altered surfactant glycoproteins contribute to impaired gas exchange.", "protein": "Pulmonary surfactant proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12544778" }, { "confidence": "high", "disease": "Cholestatic cholangiocarcinoma", "glycan_involvement": "Lp-X is an abnormal lipoprotein with altered glycosylation patterns.", "mechanism": "Cholestasis leads to accumulation of Lp-X in plasma.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "causal", "source_pmcid": "PMC12544870" }, { "confidence": "high", "disease": "Pseudohyponatremia", "glycan_involvement": "Glycosylation affects Lp-X structure and plasma distribution.", "mechanism": "High Lp-X causes laboratory artifact by displacing plasma water, falsely lowering sodium measurement.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "causal", "source_pmcid": "PMC12544870" }, { "confidence": "medium", "disease": "Hyperviscosity syndrome (HVS)", "glycan_involvement": "Glycan composition influences Lp-X aggregation and viscosity.", "mechanism": "Marked Lp-X elevation increases plasma viscosity, predisposing to HVS.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "causal", "source_pmcid": "PMC12544870" }, { "confidence": "high", "disease": "Cholestatic liver disease", "glycan_involvement": "Altered glycosylation in cholestasis promotes Lp-X formation.", "mechanism": "Lp-X is elevated in cholestatic conditions.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "biomarker", "source_pmcid": "PMC12544870" }, { "confidence": "medium", "disease": "Lecithin\u2013cholesterol acyltransferase (LCAT) deficiency", "glycan_involvement": "LCAT is a glycoprotein; its deficiency alters lipoprotein glycosylation.", "mechanism": "LCAT deficiency impairs cholesterol esterification, leading to Lp-X accumulation.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "causal", "source_pmcid": "PMC12544870" }, { "confidence": "medium", "disease": "Post-transplant graft-versus-host disease", "glycan_involvement": "Cholestasis alters glycoprotein metabolism, favoring Lp-X.", "mechanism": "Lp-X can be elevated in post-transplant GVHD with cholestasis.", "protein": "Lipoprotein X (Lp-X)", "relationship_type": "biomarker", "source_pmcid": "PMC12544870" }, { "confidence": "medium", "disease": "Cholestatic cholangiocarcinoma", "glycan_involvement": "ApoB100 glycosylation is absent in Lp-X particles.", "mechanism": "Lp-X lacks ApoB100, distinguishing it from typical LDL in cholestasis.", "protein": "Apolipoprotein B100 (ApoB100)", "relationship_type": "biomarker", "source_pmcid": "PMC12544870" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Lipoproteins are glycosylated; altered glycosylation may affect clearance and function.", "mechanism": "Elevated glycosylated lipoproteins are associated with MASLD progression.", "protein": "Lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12544894" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding and clearance.", "mechanism": "Increased LDL-C is a marker of metabolic dysfunction in MASLD.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544894" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates LDL uptake by vascular cells.", "mechanism": "Elevated LDL-C contributes to atherosclerosis in MASLD patients.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12544894" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ApoB-100 is N-glycosylated, influencing LDL structure and function.", "mechanism": "ApoB-100 is the main protein of LDL; its levels reflect lipoprotein metabolism in MASLD.", "protein": "Apolipoprotein B-100", "relationship_type": "biomarker", "source_pmcid": "PMC12544894" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects lipoprotein metabolism and clearance.", "mechanism": "Elevated triglyceride-rich lipoproteins are common in MASLD.", "protein": "Triglyceride-rich Lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12544894" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation state influences lipoprotein function.", "mechanism": "Altered glycoprotein lipoprotein levels are characteristic of dyslipidemia in MASLD.", "protein": "Lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12544894" }, { "confidence": "high", "disease": "Cholestatic liver injury", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "ALP elevation indicates cholestasis due to impaired bile flow in hypothyroidism.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544936" }, { "confidence": "high", "disease": "Cholestatic liver injury", "glycan_involvement": "GGT is a glycoprotein; glycosylation modulates its secretion and activity.", "mechanism": "GGT elevation reflects cholestasis and hepatobiliary dysfunction in hypothyroidism.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544936" }, { "confidence": "medium", "disease": "Cholestatic liver injury", "glycan_involvement": "Alpha-1 antitrypsin is highly glycosylated; glycan defects can cause liver disease.", "mechanism": "Alpha-1 antitrypsin deficiency was ruled out as a cause of liver injury.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker (excluded diagnosis)", "source_pmcid": "PMC12544936" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "Glycosylation affects ALP serum half-life.", "mechanism": "Elevated ALP is associated with jaundice in cholestatic liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544936" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "Glycosylation affects GGT secretion.", "mechanism": "Elevated GGT is associated with jaundice in cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544936" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Insulin is glycosylated, which affects its stability and receptor binding.", "mechanism": "Impaired insulin signaling due to elevated free fatty acids and obesity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Morbid Obesity", "glycan_involvement": "Leptin glycosylation modulates its secretion and receptor interaction.", "mechanism": "Leptin levels are elevated in obesity, reflecting adipose tissue mass.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is glycosylated, which may affect its stability in circulation.", "mechanism": "Elevated ALT indicates liver injury and is a marker for MASLD.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST glycosylation may influence its serum levels.", "mechanism": "Elevated AST is associated with liver dysfunction in MASLD.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Low HDL-C is a risk marker for CVD, especially in metabolic syndrome.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB) with glycosylation impacting atherogenicity.", "mechanism": "Elevated LDL-C is a risk marker for CVD.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Insulin glycosylation affects receptor binding and metabolic signaling.", "mechanism": "Insulin resistance promotes hepatic steatosis and MASLD progression.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation may affect ALT's serum half-life.", "mechanism": "Elevated ALT correlates with severity of insulin resistance.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Leptin glycosylation modulates its bioactivity.", "mechanism": "Leptin levels reflect adiposity and are associated with insulin resistance.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation of HDL-associated proteins affects lipid metabolism.", "mechanism": "Low HDL-C is a marker for metabolic syndrome.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12544940" }, { "confidence": "high", "disease": "Anencephaly", "glycan_involvement": "AFP is a glycoprotein; glycosylation is essential for its stability and detection.", "mechanism": "Elevated maternal serum AFP indicates neural tube defects such as anencephaly.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Omphalocele", "glycan_involvement": "Glycosylation enables immunoassay detection.", "mechanism": "Elevated maternal serum AFP can indicate abdominal wall defects like omphalocele.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Spina bifida", "glycan_involvement": "Glycosylation required for immunoassay recognition.", "mechanism": "High AFP in maternal serum is a marker for neural tube defects including spina bifida.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects serum stability and immunoassay detection.", "mechanism": "Elevated AFP in adults is indicative of primary liver cancer.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Germ cell tumours", "glycan_involvement": "Glycosylation required for immunoassay detection.", "mechanism": "Increased AFP is a marker for certain germ cell tumours.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "medium", "disease": "Chronic active hepatitis", "glycan_involvement": "Glycosylation enables serum detection.", "mechanism": "AFP levels can be elevated in chronic liver inflammation.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Normal pregnancy", "glycan_involvement": "Glycosylation required for function and detection.", "mechanism": "AFP is physiologically elevated during first and second trimesters.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544960" }, { "confidence": "high", "disease": "Thyroid cancer", "glycan_involvement": "Integrin \u03b1V\u03b23 is a glycoprotein; glycosylation is essential for its cell surface localization and function.", "mechanism": "\u03b1V\u03b23 is overexpressed in thyroid cancer tissues compared to normal thyroid.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12545272" }, { "confidence": "high", "disease": "Papillary thyroid cancer", "glycan_involvement": "Glycosylation supports receptor stability and ligand binding.", "mechanism": "Significantly higher expression of \u03b1V\u03b23 in papillary thyroid cancer compared to follicular and normal thyroid.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12545272" }, { "confidence": "high", "disease": "BRAF-like thyroid cancer", "glycan_involvement": "Glycosylation required for proper receptor function and cell surface expression.", "mechanism": "BRAF-like thyroid cancers have increased \u03b1V\u03b23 expression; high expression correlates with therapeutic response.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12545272" }, { "confidence": "high", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation enables ligand (RGD) binding and receptor targeting.", "mechanism": "Targeting \u03b1V\u03b23 with 177Lu-EB-RGD inhibits tumor growth in models with high \u03b1V\u03b23 expression.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545272" }, { "confidence": "medium", "disease": "RAS-like thyroid cancer", "glycan_involvement": "Glycosylation status may affect expression levels.", "mechanism": "RAS-like thyroid cancers have lower \u03b1V\u03b23 expression compared to BRAF-like.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12545272" }, { "confidence": "medium", "disease": "Follicular thyroid cancer", "glycan_involvement": "Glycosylation supports receptor function.", "mechanism": "Lower \u03b1V\u03b23 expression in follicular thyroid cancer compared to papillary subtype.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12545272" }, { "confidence": "medium", "disease": "Poorly differentiated thyroid cancer", "glycan_involvement": "Glycosylation maintains receptor structure.", "mechanism": "No significant difference in \u03b1V\u03b23 expression compared to papillary thyroid cancer.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12545272" }, { "confidence": "high", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation critical for receptor-ligand interaction.", "mechanism": "Combination therapy (177Lu-EB-RGD + Lenvatinib) further reduces tumor growth in high \u03b1V\u03b23 expressing models.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545272" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation of Factor VIII is essential for its stability and function; altered glycosylation may affect its clearance and activity in liver failure.", "mechanism": "Elevated Factor VIII activity observed in acute liver failure, reflecting endothelial activation and coagulopathy.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12545282" }, { "confidence": "medium", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation modulates Factor VIII half-life and immunogenicity, which may be altered in hypermetabolic states.", "mechanism": "Factor VIII activity is elevated during thyroid storm, possibly due to systemic inflammation and endothelial activation.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12545282" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "Glycosylation of TSHR affects its antigenicity and autoantibody binding.", "mechanism": "Autoantibodies bind to TSHR, stimulating thyroid hormone production and leading to hyperthyroidism.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC12545352" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "Glycosylation of TPO modulates its immunogenicity and antibody recognition.", "mechanism": "Anti-TPO antibodies are elevated in Graves' disease, indicating autoimmune activity.", "protein": "Thyroid Peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC12545352" }, { "confidence": "high", "disease": "Primary hyperthyroidism", "glycan_involvement": "Glycosylation influences receptor conformation and immune recognition.", "mechanism": "TSHR activation by autoantibodies drives excess thyroid hormone production.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC12545352" }, { "confidence": "medium", "disease": "Neuropsychiatric symptoms (psychosis, delirium, agitation)", "glycan_involvement": "Glycosylation may affect TSHR autoantibody binding and downstream effects.", "mechanism": "TSHR autoantibody-mediated hyperthyroidism leads to adrenergic hyperactivity and psychiatric symptoms.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC12545352" }, { "confidence": "medium", "disease": "Neuropsychiatric symptoms (psychosis, delirium, agitation)", "glycan_involvement": "Glycosylation modulates TPO antigenicity and immune response.", "mechanism": "Elevated anti-TPO antibodies correlate with autoimmune thyroid activity and neuropsychiatric manifestations.", "protein": "Thyroid Peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC12545352" }, { "confidence": "high", "disease": "Osteogenesis Imperfecta Type I", "glycan_involvement": "Collagen glycosylation affects fibril formation and stability.", "mechanism": "Mutations in COL1A1/COL1A2 impair collagen synthesis and structure, leading to bone fragility.", "protein": "Type I Collagen (COL1A1/COL1A2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Altered glycosylation may further impair collagen function.", "mechanism": "Defective collagen reduces bone mass and increases fracture risk.", "protein": "Type I Collagen (COL1A1/COL1A2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "high", "disease": "A1AT Deficiency", "glycan_involvement": "Glycosylation is essential for A1AT stability and secretion.", "mechanism": "Deficiency leads to liver and lung disease.", "protein": "Alpha-1-antitrypsin (A1AT)", "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "high", "disease": "LAL Deficiency", "glycan_involvement": "Glycosylation required for lysosomal targeting.", "mechanism": "Deficiency causes lipid accumulation and liver dysfunction.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "medium", "disease": "Iron Overload", "glycan_involvement": "Altered glycosylation affects iron binding and transport.", "mechanism": "Transferrin glycoforms are used to assess iron metabolism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545356" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "Glycosylation modulates immune function.", "mechanism": "Elevated immunoglobulins indicate autoimmune 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0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "potential causal", "source_pmcid": "PMC12545356" }, { "confidence": "high", "disease": "Bone Fragility", "glycan_involvement": "Glycosylation influences collagen cross-linking and strength.", "mechanism": "Defective collagen leads to increased fracture rate.", "protein": "Type I Collagen (COL1A1/COL1A2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "medium", "disease": "Functional Disability", "glycan_involvement": "Indirect; altered glycosylation may worsen bone quality.", "mechanism": "Bone fragility and fractures result in mobility impairment.", "protein": "Type I Collagen (COL1A1/COL1A2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12545356" }, { "confidence": "high", "disease": "Adrenocortical carcinoma (ACC)", "glycan_involvement": "WNT5A is a glycoprotein; glycosylation may affect its secretion and paracrine signaling, influencing immune modulation.", "mechanism": "WNT5A upregulation promotes tumor progression by inducing myeloid-mediated immune tolerance, leading to poor anti-tumor myeloid response and increased tumorigenesis.", "protein": "WNT5A", "relationship_type": "causal", "source_pmcid": "PMC12545465" }, { "confidence": "high", "disease": "Adrenocortical carcinoma (ACC)", "glycan_involvement": "Glycosylation of WNT5A may be essential for its extracellular activity and immune modulatory function.", "mechanism": "Loss or antagonism of WNT5A enhances myeloid cell infiltration and anti-tumor activity, reducing ACC tumorigenesis and improving survival.", "protein": "WNT5A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545465" }, { "confidence": "high", "disease": "Adrenocortical carcinoma (ACC)", "glycan_involvement": "Glycosylation status may influence WNT5A detection and quantification as a biomarker.", "mechanism": "Low WNT5A expression in human ACC tumors correlates with favorable overall survival and enhanced anti-tumor myeloid immune functions.", "protein": "WNT5A", "relationship_type": "biomarker", "source_pmcid": "PMC12545465" }, { "confidence": "high", "disease": "Paget\u2019s disease of bone (PDB)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "Elevated ALP reflects increased bone turnover in PDB.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). 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Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545498" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "GGT is elevated in liver disease, reflecting cholestasis and hepatobiliary injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545498" }, { "confidence": "medium", "disease": "Primary biliary cirrhosis", "glycan_involvement": "Glycosylation modulates ALP isoform distribution in serum.", "mechanism": "ALP is elevated in primary biliary cirrhosis due to bile duct injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). 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Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545498" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "CD52 is a glycoprotein; glycosylation is essential for antibody recognition.", "mechanism": "Alemtuzumab targets CD52 on mature leukocytes, leading to immunomodulation and reduced MS activity.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545673" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "Glycosylation of CD52 may affect antibody binding and immune cell targeting.", "mechanism": "Alemtuzumab-induced depletion of CD52+ cells leads to immune reconstitution and secondary autoimmunity, including Graves' disease.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC12545673" }, { "confidence": "high", "disease": "Thyroid Eye Disease (TED)", "glycan_involvement": "Glycosylation of CD52 is required for Alemtuzumab binding.", "mechanism": "Alemtuzumab-induced immune dysregulation via CD52 targeting can trigger TED as a secondary autoimmune complication.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC12545673" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSHR glycosylation affects receptor conformation and autoantibody recognition.", "mechanism": "Autoantibodies activate TSHR, leading to hyperthyroidism in Graves' disease.", "protein": "TSHR", "relationship_type": "causal", "source_pmcid": "PMC12545673" }, { "confidence": "high", "disease": "Thyroid Eye Disease (TED)", "glycan_involvement": "Glycosylation of TSHR modulates antibody binding and tissue-specific activation.", "mechanism": "Autoantibody-mediated activation of TSHR in orbital tissues drives TED pathogenesis.", "protein": "TSHR", "relationship_type": "causal", "source_pmcid": "PMC12545673" }, { "confidence": "high", "disease": "Malignant Struma Ovarii", "glycan_involvement": "N-glycosylation affects thyroglobulin stability and secretion, influencing its biomarker utility.", "mechanism": "Elevated serum thyroglobulin reflects presence and recurrence of thyroid tissue-derived tumor cells.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). 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The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545676" }, { "confidence": "medium", "disease": "Malignant Struma Ovarii", "glycan_involvement": "Glycosylation affects thyroglobulin clearance and immune recognition.", "mechanism": "Thyroglobulin levels guide radioactive iodine therapy and TSH suppression.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545676" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "GLP-1 receptor is a glycoprotein; glycosylation affects receptor stability and ligand binding.", "mechanism": "Activation by GLP-1 RAs reduces hepatic steatosis, inflammation, and fibrosis.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545729" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Semaglutide is a glycopeptide; glycosylation enhances stability and bioactivity.", "mechanism": "Semaglutide resolves NASH and improves liver biomarkers; limited impact on fibrosis regression.", "protein": "Semaglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Liraglutide is a glycopeptide; glycosylation improves pharmacokinetics.", "mechanism": "Liraglutide contributes to NASH resolution and fibrosis stabilization.", "protein": "Liraglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Tirzepatide is a glycopeptide; glycosylation affects drug stability.", "mechanism": "Tirzepatide reduces inflammatory and fibrotic markers more effectively than dulaglutide.", "protein": "Tirzepatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Dulaglutide is a glycopeptide; glycosylation impacts half-life.", "mechanism": "Dulaglutide reduces fibrosis and inflammation, but less effectively than tirzepatide.", "protein": "Dulaglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Exenatide is a glycopeptide; glycosylation increases resistance to degradation.", "mechanism": "Exenatide improves liver function and fibrosis scores, especially in severe obesity.", "protein": "Exenatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Receptor glycosylation modulates ligand interaction.", "mechanism": "GLP-1 RAs improve insulin resistance and glycemic control.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545729" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation maintains peptide stability.", "mechanism": "Semaglutide has limited efficacy in fibrosis regression.", "protein": "Semaglutide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation enhances drug action.", "mechanism": "Exenatide improves metabolic parameters in severe obesity.", "protein": "Exenatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12545729" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Receptor glycosylation affects cell signaling.", "mechanism": "GLP-1 RAs target receptor to reduce fibrosis progression.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545729" }, { "confidence": "high", "disease": "Paget's disease of bone (PDB)", "glycan_involvement": "N-glycosylation is essential for ALP stability and secretion; altered glycosylation may affect serum levels.", "mechanism": "Elevated bone-specific ALP reflects increased osteoblastic activity and bone turnover in PDB.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545752" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation affects ALP activity and half-life in circulation.", "mechanism": "Elevated ALP may indicate increased bone turnover in osteoporosis, especially when secondary to metabolic causes.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545752" }, { "confidence": "high", "disease": "Hypophosphatemia", "glycan_involvement": "O-glycosylation at Thr178 is required for FGF23 secretion and activity.", "mechanism": "FGF23 regulates phosphate homeostasis; abnormal FGF23 can cause hypophosphatemia.", "protein": "Fibroblast growth factor 23 (FGF23)", "relationship_type": "causal", "source_pmcid": "PMC12545752" }, { "confidence": "medium", "disease": "Paget's disease of bone (PDB)", "glycan_involvement": "O-glycosylation modulates FGF23 stability and function.", "mechanism": "Normal FGF23 levels help exclude FGF23-mediated hypophosphatemic bone disease in PDB differential diagnosis.", "protein": "Fibroblast growth factor 23 (FGF23)", "relationship_type": "biomarker", "source_pmcid": "PMC12545752" }, { "confidence": "high", "disease": "Glass Syndrome (SATB2-Associated Syndrome)", "glycan_involvement": "ALP is a glycoprotein; glycosylation is required for its stability and activity.", "mechanism": "Elevated bone-specific ALP reflects increased bone turnover due to impaired osteoblast function in SATB2 mutation.", "protein": "Alkaline phosphatase (bone-specific)", "relationship_type": "biomarker", "source_pmcid": "PMC12546060" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects ALP secretion and function.", "mechanism": "Elevated ALP indicates high bone turnover and bone loss.", "protein": "Alkaline phosphatase (bone-specific)", "relationship_type": "biomarker", "source_pmcid": "PMC12546060" }, { "confidence": "high", "disease": "Bone fragility/fractures", "glycan_involvement": "Glycosylation is essential for ALP enzymatic activity.", "mechanism": "High ALP correlates with increased bone remodeling and fracture risk.", "protein": "Alkaline phosphatase (bone-specific)", "relationship_type": "biomarker", "source_pmcid": "PMC12546060" }, { "confidence": "high", "disease": "Glass Syndrome (SATB2-Associated Syndrome)", "glycan_involvement": "Indirect; SATB2 regulates expression of glycoproteins involved in bone matrix.", "mechanism": "SATB2 mutation disrupts osteoblast differentiation and matrix formation, causing bone fragility.", "protein": "SATB2", "protein_enriched": { "function": "Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by", "gene_name": "SATB2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UPW6" }, "relationship_type": "causal", "source_pmcid": "PMC12546060" }, { "confidence": "medium", "disease": "Osteopenia", "glycan_involvement": "Indirect via regulation of glycoprotein genes.", "mechanism": "Impaired SATB2 function leads to reduced bone density.", "protein": "SATB2", "protein_enriched": { "function": "Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by", "gene_name": "SATB2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UPW6" }, "relationship_type": "causal", "source_pmcid": "PMC12546060" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Indirect via osteoblast gene regulation.", "mechanism": "Loss of SATB2 impairs bone mineralization, leading to osteoporosis.", "protein": "SATB2", "protein_enriched": { "function": "Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by", "gene_name": "SATB2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9UPW6" }, "relationship_type": "causal", "source_pmcid": "PMC12546060" }, { "confidence": "high", "disease": "Doege-Potter syndrome", "glycan_involvement": "IGF-II is a glycoprotein; glycosylation affects its stability and bioactivity.", "mechanism": "Ectopic secretion of IGF-II by mesenchymal tumors leads to hypoglycemia.", "protein": "IGF-II", "relationship_type": "causal", "source_pmcid": "PMC12546260" }, { "confidence": "high", "disease": "Hypoglycemia", "glycan_involvement": "Glycosylation modulates IGF-II half-life and receptor binding.", "mechanism": "Excess IGF-II mimics insulin action, lowering blood glucose.", "protein": "IGF-II", "relationship_type": "causal", "source_pmcid": "PMC12546260" }, { "confidence": "medium", "disease": "Hypertrophic osteoarthropathy", "glycan_involvement": "Glycosylation may influence IGF-II tissue distribution.", "mechanism": "Paraneoplastic IGF-II may contribute to bone and joint changes.", "protein": "IGF-II", "relationship_type": "causal", "source_pmcid": "PMC12546260" }, { "confidence": "medium", "disease": "Acanthosis nigricans", "glycan_involvement": "Glycosylation affects IGF-II signaling in skin.", "mechanism": "Paraneoplastic IGF-II can induce skin changes.", "protein": "IGF-II", "relationship_type": "causal", "source_pmcid": "PMC12546260" }, { "confidence": "medium", "disease": "Seborrheic hyperkeratosis", "glycan_involvement": "Glycosylation modulates IGF-II activity in skin.", "mechanism": "Paraneoplastic IGF-II may drive keratinocyte proliferation.", "protein": "IGF-II", "relationship_type": "causal", "source_pmcid": "PMC12546260" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "Proinsulin is glycosylated, affecting secretion and clearance.", "mechanism": "Elevated proinsulin can indicate non-insulinoma hypoglycemia.", "protein": "Proinsulin", "relationship_type": "biomarker", "source_pmcid": "PMC12546260" }, { "confidence": "medium", "disease": "Doege-Potter syndrome", "glycan_involvement": "IGF-I glycosylation affects its serum levels.", "mechanism": "Low IGF-I/IGF-II ratio supports diagnosis.", "protein": "IGF-I", "relationship_type": "biomarker", "source_pmcid": "PMC12546260" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects processing and aggregation.", "mechanism": "A\u03b2 accumulation forms extracellular plaques; impaired autophagy leads to reduced clearance and increased neurotoxicity.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Late-onset Alzheimer's disease (LOAD)", "glycan_involvement": "APOE is N-glycosylated; glycosylation modulates lipid binding and clearance functions.", "mechanism": "APOE4 is a major genetic risk factor; impairs autophagy and mitophagy, increases A\u03b2 and Tau pathology.", "protein": "Apolipoprotein E4 (APOE4)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Early-onset familial Alzheimer's disease (EOFAD)", "glycan_involvement": "PSEN1 is glycosylated; glycosylation may affect \u03b3-secretase complex assembly.", "mechanism": "Mutations disrupt autophagy and lysosomal acidification, leading to A\u03b2 and Tau accumulation.", "protein": "Presenilin 1 (PSEN1)", "relationship_type": "causal", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation and degradation.", "mechanism": "Hyperphosphorylated Tau forms neurofibrillary tangles; impaired autophagy reduces Tau degradation.", "protein": "Tau (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation required for cell surface expression and function.", "mechanism": "TREM2 mutations increase AD risk; loss impairs autophagy and microglial A\u03b2 clearance.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12546301" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "SQSTM1 is O-glycosylated; glycosylation may affect protein-protein interactions.", "mechanism": "Increased p62 indicates impaired autophagy; accumulates in AD brains.", "protein": "Sequestosome 1 (SQSTM1/p62)", "relationship_type": "biomarker", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Beclin1 is O-glycosylated; glycosylation may regulate autophagy initiation.", "mechanism": "Reduced Beclin1 impairs autophagy, increases amyloid plaques and neurodegeneration.", "protein": "Beclin1", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12546301" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "VCP is N-glycosylated; glycosylation may affect protein stability.", "mechanism": "Decreased VCP impairs autophagy and Tau degradation.", "protein": "Valosin-containing protein (VCP/p97)", "protein_enriched": { "function": "Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membra", "gene_name": "VCP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55072" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12546301" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "GPNMB is heavily N-glycosylated; glycosylation is essential for function.", "mechanism": "Upregulation via LINC00672 promotes autophagosome formation and clearance of A\u03b2 and Tau.", "protein": "Glycoprotein non-metastatic melanoma protein B (GPNMB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12546301" }, { "confidence": "medium", "disease": "Early-onset familial Alzheimer's disease (EOFAD)", "glycan_involvement": "PSEN2 is glycosylated; glycosylation may affect trafficking and function.", "mechanism": "Mutations impair autophagy by reducing RAB7 recruitment, leading to lysosomal dysfunction.", "protein": "Presenilin 2 (PSEN2)", "relationship_type": "causal", "source_pmcid": "PMC12546301" }, { "confidence": "high", "disease": "Graves disease", "glycan_involvement": "TSI glycosylation affects autoantibody stability and receptor binding.", "mechanism": "TSI binds and activates TSHR, stimulating excess thyroid hormone production.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC12546525" }, { "confidence": "high", "disease": "Graves disease", "glycan_involvement": "TSHR N-glycosylation modulates receptor conformation and autoantibody recognition.", "mechanism": "TSHR is activated by TSI, leading to hyperthyroidism.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC12546525" }, { "confidence": "medium", "disease": "Graves disease", "glycan_involvement": "TSH glycosylation affects its half-life and receptor interaction.", "mechanism": "Suppressed TSH is a diagnostic marker for Graves disease.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12546525" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation influences TSH bioactivity.", "mechanism": "Low TSH indicates thyrotoxicosis.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12546525" }, { "confidence": "medium", "disease": "High-output heart failure", "glycan_involvement": "Pro-BNP glycosylation affects its stability and detection.", "mechanism": "Elevated pro-BNP reflects cardiac stress and heart failure.", "protein": "Pro-BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12546525" }, { "confidence": "high", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation modulates TSI pathogenicity.", "mechanism": "TSI-induced TSHR activation causes excessive thyroid hormone release.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC12546525" }, { "confidence": "medium", "disease": "High-output heart failure", "glycan_involvement": "Glycosylation may influence TSI activity and disease severity.", "mechanism": "TSI-driven thyrotoxicosis increases cardiac output, leading to heart failure.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC12546525" }, { "confidence": "low", "disease": "Pulmonary hypertension", "glycan_involvement": "Glycosylation may affect TSI-mediated vascular effects.", "mechanism": "TSI-induced thyrotoxicosis increases pulmonary vascular resistance.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC12546525" }, { "confidence": "high", "disease": "CALFAN syndrome (SCYL1 deficiency)", "glycan_involvement": "Secondary glycosylation defects during liver crises due to Golgi dysfunction.", "mechanism": "Biallelic pathogenic variants in SCYL1 disrupt vesicular trafficking, leading to hepatic and neurological manifestations.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "high", "disease": "Acute liver failure (ALF)", "glycan_involvement": "Transient glycosylation abnormalities observed during ALF episodes.", "mechanism": "SCYL1 deficiency increases ER stress and impairs hepatocyte function, causing recurrent ALF.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation (CDG)-like phenotype", "glycan_involvement": "Disrupted N-glycan processing due to temporary Golgi dysfunction.", "mechanism": "Transient abnormal glycosylation patterns (Type I and II) detected during liver crises.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "Low-GGT cholestasis", "glycan_involvement": "Glycosylation defects are secondary to liver dysfunction.", "mechanism": "Defective vesicular trafficking impairs bile secretion, resulting in cholestasis with low GGT.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "Neurodevelopmental delay", "glycan_involvement": "Not directly linked to glycosylation in this report.", "mechanism": "SCYL1 deficiency affects neuronal vesicular trafficking, leading to hypotonia and developmental delay.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "high", "disease": "CALFAN syndrome (SCYL1 deficiency)", "glycan_involvement": "Altered N-glycosylation patterns (CDT, N-glycan profile).", "mechanism": "Abnormal glycoforms detected during liver crises, normalizing after recovery.", "protein": "Glycoproteins (e.g., transferrin)", "relationship_type": "biomarker", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "Transient glycosylation defects during liver crises", "glycan_involvement": "Similar mechanism to SCYL1; affects N-glycan processing.", "mechanism": "NBAS deficiency also causes vesicular trafficking defects and secondary glycosylation abnormalities.", "protein": "NBAS", "protein_enriched": { "function": "Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B (PubMed:12221131, PubMed:26824392). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into the", "gene_name": "RAB3IP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96QF0" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "Transient glycosylation defects during liver crises", "glycan_involvement": "Affects N-glycan maturation.", "mechanism": "RINT1 deficiency disrupts ER-Golgi trafficking, leading to glycosylation defects during hepatic stress.", "protein": "RINT1", "protein_enriched": { "function": "Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the NRZ complex which is believed to play a ro", "gene_name": "RINT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6NUQ1" }, "relationship_type": "causal", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "CALFAN syndrome (SCYL1 deficiency)", "glycan_involvement": "No glycosylation abnormalities in asymptomatic individuals.", "mechanism": "Some individuals with biallelic SCYL1 variants remain asymptomatic, suggesting modifying factors.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "protective", "source_pmcid": "PMC12550320" }, { "confidence": "medium", "disease": "CALFAN syndrome (SCYL1 deficiency)", "glycan_involvement": "Glycosylation defects are reversible with hepatic recovery.", "mechanism": "Recovery of liver function leads to normalization of glycosylation, suggesting reversibility.", "protein": "SCYL1", "protein_enriched": { "function": "Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morp", "gene_name": "SCYL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KG9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12550320" }, { "confidence": "high", "disease": "Cancer (colon, skin, breast)", "glycan_involvement": "Remodeling of high-mannose to complex N-glycans on glycoproteins.", "mechanism": "MII is overexpressed in these cancers, leading to altered glycoforms on cell membrane glycoproteins, which correlates with metastasis and disease progression.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12550843" }, { "confidence": "high", "disease": "Metastasis", "glycan_involvement": "Formation of complex N-glycans on cell surface glycoproteins.", "mechanism": "Altered N-glycan processing by MII promotes glycoform changes that facilitate metastasis.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "causal", "source_pmcid": "PMC12550843" }, { "confidence": "high", "disease": "Cancer (colon, skin, breast)", "glycan_involvement": "Blocks N-glycan maturation on glycoproteins.", "mechanism": "Inhibition of MII reduces complex N-glycan formation, associated with reduced tumor growth and metastasis.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12550843" }, { "confidence": "medium", "disease": "Congenital disorders of glycosylation", "glycan_involvement": "Impaired N-glycan maturation.", "mechanism": "Defects or inhibition in MII activity disrupt N-glycan processing, underlying some glycosylation disorders.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12550843" }, { "confidence": "medium", "disease": "Viral infections", "glycan_involvement": "Disrupts viral glycoprotein N-glycan maturation.", "mechanism": "MII inhibitors are explored as antivirals by altering viral glycoprotein processing.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12550843" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Affects N-glycan structures on metabolic enzymes/receptors.", "mechanism": "MII inhibitors are considered for diabetes therapy by modulating glycoprotein processing.", "protein": "Golgi alpha-mannosidase II (MII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12550843" }, { "confidence": "medium", "disease": "Congenital disorders of glycosylation", "glycan_involvement": "Blocks trimming of high-mannose N-glycans.", "mechanism": "MI is critical for N-glycan maturation; defects can cause glycosylation disorders.", "protein": "Endoplasmic reticulum alpha-mannosidase I (MI)", "relationship_type": "causal", "source_pmcid": "PMC12550843" }, { "confidence": "low", "disease": "Protein misfolding diseases", "glycan_involvement": "Affects N-glycan-dependent quality control.", "mechanism": "MI participates in degradation of misfolded glycoproteins; dysfunction may contribute to disease.", "protein": "Endoplasmic reticulum alpha-mannosidase I (MI)", "relationship_type": "causal", "source_pmcid": "PMC12550843" }, { "confidence": "low", "disease": "Congenital disorders of glycosylation", "glycan_involvement": "Impaired degradation of N-glycans.", "mechanism": "L-MII is involved in glycan catabolism; defects cause lysosomal storage diseases.", "protein": "Lysosomal alpha-mannosidase (L-MII)", "relationship_type": "causal", "source_pmcid": "PMC12550843" }, { "confidence": "medium", "disease": "Cancer (colon, skin, breast)", "glycan_involvement": "Changes in N-glycan branching and composition.", "mechanism": "Altered N-glycan structures on cell surface glycoproteins serve as cancer biomarkers.", "protein": "N-glycosylated cell membrane glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12550843" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Defective glycosylation leads to abnormal APP processing and amyloid-beta accumulation.", "mechanism": "Impaired sialylation affects glycoprotein biosynthesis, altering synaptic connectivity and APP processing.", "protein": "ST3GAL3", "relationship_type": "causal", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "ADHD", "glycan_involvement": "Aberrant glycosylation affects synaptic glycoproteins.", "mechanism": "Mutations disrupt glycosylation, impairing neuronal communication and cognitive function.", "protein": "ST3GAL3", "relationship_type": "causal", "source_pmcid": "PMC12550898" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Altered N-glycosylation modulates APP cleavage and aggregation.", "mechanism": "APP glycosylation status influences amyloid-beta production and plaque formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "ADHD", "glycan_involvement": "Glycosylation may affect APP trafficking and synaptic function.", "mechanism": "APP variants linked to cognitive deficits in ADHD, possibly via synaptic dysfunction.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12550898" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates APOE structure and amyloid interaction.", "mechanism": "APOE \u03b54 allele promotes amyloid-beta aggregation and impairs clearance.", "protein": "APOE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "ADHD", "glycan_involvement": "Glycosylation may influence APOE's neuroprotective functions.", "mechanism": "APOE \u03b54 associated with cognitive dysfunction in ADHD.", "protein": "APOE", "relationship_type": "risk factor", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Sorting receptor glycosylation affects APP interaction.", "mechanism": "Regulates APP processing and amyloid-beta production.", "protein": "SORCS2", "protein_enriched": { "function": "", "gene_name": "SORCS1", "glycan_count": 3, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G83460ZZ", "G28541PG", "G80920RR" ], "uniprot_id": "Q8WY21" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "ADHD", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Disrupts synaptic transmission and plasticity, contributing to cognitive deficits.", "protein": "SORCS3", "protein_enriched": { "function": "Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CPAP (PubMed:19052644). Required for anchoring microtubules to the centrosomes and for t", "gene_name": "CEP350", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5VT06" }, "relationship_type": "causal", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects vesicle fusion and neurotransmitter release.", "mechanism": "Reduced levels contribute to synaptic dysfunction in AD.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC12550898" }, { "confidence": "medium", "disease": "ADHD", "glycan_involvement": "Glycosylation may modulate synaptic activity.", "mechanism": "Polymorphisms alter dopamine signaling and synaptic vesicle recycling.", "protein": "SNAP25", "relationship_type": "causal", "source_pmcid": "PMC12550898" }, { "confidence": "high", "disease": "XMEN syndrome", "glycan_involvement": "Defective N-glycosylation of immune glycoproteins", "mechanism": "Loss-of-function variants in MAGT1 impair N-glycosylation, leading to immunodeficiency.", "protein": "MAGT1", "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "XMEN syndrome", "glycan_involvement": "N-glycosylation required for stable surface expression", "mechanism": "Reduced NKG2D surface expression due to impaired N-glycosylation decreases cytotoxic cell activation.", "protein": "NKG2D", "protein_enriched": { "function": "Involved in pre-mRNA splicing process (PubMed:11991638, PubMed:12084575, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre", "gene_name": "CRNKL1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10488MI", "G49108TO" ], "uniprot_id": "Q9BZJ0" }, "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "XMEN syndrome", "glycan_involvement": "N-glycosylation required for surface expression", "mechanism": "Decreased CD28 expression from defective N-glycosylation impairs T-cell co-stimulation.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation", "glycan_involvement": "Altered N-glycan branching and sialylation", "mechanism": "Abnormal transferrin glycoforms indicate systemic N-glycosylation defects.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "XMEN syndrome", "glycan_involvement": "N-glycosylation important for perforin transport and stability", "mechanism": "Reduced perforin expression impairs cytotoxic lymphocyte function, increasing infection and autoimmunity risk.", "protein": "Perforin", "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "medium", "disease": "Autoimmune cytopenia", "glycan_involvement": "Impaired glycosylation of immune regulatory proteins", "mechanism": "MAGT1 deficiency leads to immune dysregulation and severe autoimmune cytopenias.", "protein": "MAGT1", "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "medium", "disease": "EBV-associated B-cell malignancy", "glycan_involvement": "N-glycosylation defects in immune receptors", "mechanism": "Impaired immune surveillance due to defective glycoprotein expression increases malignancy risk.", "protein": "MAGT1", "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "medium", "disease": "Familial hemophagocytic lymphohistiocytosis (FHL)", "glycan_involvement": "N-glycosylation affects perforin trafficking", "mechanism": "Perforin deficiency causes cytotoxic dysfunction, similar to XMEN syndrome.", "protein": "Perforin", "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "Recurrent viral infections", "glycan_involvement": "N-glycosylation required for receptor function", "mechanism": "Reduced NKG2D impairs NK and CD8+ T-cell antiviral responses.", "protein": "NKG2D", "protein_enriched": { "function": "Involved in pre-mRNA splicing process (PubMed:11991638, PubMed:12084575, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre", "gene_name": "CRNKL1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10488MI", "G49108TO" ], "uniprot_id": "Q9BZJ0" }, "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "medium", "disease": "Autoimmune haemolytic anaemia", "glycan_involvement": "N-glycosylation required for CD28 function", "mechanism": "Impaired CD28 expression disrupts immune tolerance, predisposing to autoimmunity.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC12551146" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "ApoB is N-glycosylated, which affects its secretion and function in lipoprotein metabolism.", "mechanism": "ApoB reflects the number of atherogenic lipoprotein particles; higher ApoB predicts increased CVD risk.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "Youth-onset type 2 diabetes (Y-T2D)", "glycan_involvement": "N-glycosylation modulates ApoB stability and plasma levels.", "mechanism": "Elevated ApoB is associated with higher predicted CVD risk in Y-T2D youth.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "hsCRP is N-glycosylated, which influences its plasma half-life and function.", "mechanism": "hsCRP is a marker of systemic inflammation; higher levels predict increased CVD risk.", "protein": "High sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "Youth-onset type 2 diabetes (Y-T2D)", "glycan_involvement": "N-glycosylation affects hsCRP's inflammatory activity.", "mechanism": "Elevated hsCRP is associated with higher predicted CVD risk in Y-T2D youth.", "protein": "High sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Represents N-acetylglucosamine residues on circulating glycoproteins.", "mechanism": "GlycA reflects the aggregate N-acetyl methyl signals from multiple acute-phase glycoproteins; higher GlycA predicts increased CVD risk.", "protein": "Glycoprotein acetylation (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "medium", "disease": "Youth-onset type 2 diabetes (Y-T2D)", "glycan_involvement": "Reflects increased glycosylation of acute-phase proteins in inflammation.", "mechanism": "Elevated GlycA is associated with higher predicted CVD risk in Y-T2D youth.", "protein": "Glycoprotein acetylation (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "LDL particles contain ApoB, a glycoprotein; glycosylation affects LDL metabolism.", "mechanism": "Higher LDL-P number predicts increased CVD risk, even when LDL-C is normal.", "protein": "Low-density lipoprotein particle (LDL-P)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "Youth-onset type 2 diabetes (Y-T2D)", "glycan_involvement": "ApoB glycosylation influences LDL particle number and atherogenicity.", "mechanism": "Elevated LDL-P is associated with higher predicted CVD risk in Y-T2D youth.", "protein": "Low-density lipoprotein particle (LDL-P)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates hsCRP's interaction with immune cells.", "mechanism": "hsCRP is involved in vascular inflammation and is predictive of atherosclerotic progression.", "protein": "High sensitivity C-reactive protein (hsCRP)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Represents glycosylation changes in acute-phase proteins during inflammation.", "mechanism": "GlycA is associated with subclinical atherosclerosis and systemic inflammation.", "protein": "Glycoprotein acetylation (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12551294" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "HLA glycoprotein structure (glycosylation) affects antigen binding groove.", "mechanism": "Weak binding to HHV antigens leads to poor antigen presentation and viral persistence.", "protein": "HLA Class I (C*07:04)", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Glycosylation modulates HLA peptide presentation.", "mechanism": "Weak binding to HHV antigens impairs adaptive immunity, allowing chronic infection.", "protein": "HLA Class II (DQB1*03:03)", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Glycosylation supports optimal antigen presentation.", "mechanism": "Strong binding to HHV antigens enables efficient immune clearance.", "protein": "HLA Class I (B*08:01)", "relationship_type": "protective", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Glycosylation influences HLA structure and function.", "mechanism": "Strong binding to HHV antigens promotes robust adaptive immunity.", "protein": "HLA Class II (DPB1*02:01)", "relationship_type": "protective", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "Long COVID", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, affecting immune recognition.", "mechanism": "Weak binding of spike glycoprotein peptides to ME/CFS risk HLA alleles allows viral antigen persistence.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "PTLDS", "glycan_involvement": "Envelope proteins and peptidoglycan are glycosylated, influencing immune evasion.", "mechanism": "Weak binding to ME/CFS risk HLA alleles leads to persistence of bacterial antigens.", "protein": "Borrelia burgdorferi envelope proteins (including peptidoglycan)", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Viral glycoprotein glycosylation affects antigenicity.", "mechanism": "Weak HLA binding (risk alleles) to HHV6A glycoprotein peptides correlates with increased ME/CFS risk.", "protein": "HHV6A glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Weak HLA binding (risk alleles) to HHV6B glycoprotein peptides correlates with increased ME/CFS risk.", "protein": "HHV6B glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS", "glycan_involvement": "Glycosylation impacts antigen presentation.", "mechanism": "Weak HLA binding (risk alleles) to HHV7 glycoprotein peptides correlates with increased ME/CFS risk.", "protein": "HHV7 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "ME/CFS, Long COVID, PTLDS", "glycan_involvement": "N-glycosylation of HLA molecules is essential for proper folding and antigen presentation.", "mechanism": "HLA glycoprotein polymorphism and glycosylation determine antigen binding and disease susceptibility.", "protein": "HLA glycoproteins (general)", "relationship_type": "causal/protective", "source_pmcid": "PMC12552462" }, { "confidence": "high", "disease": "Lysosomal storage diseases (LSDs)", "glycan_involvement": "Glycosylation is essential for lysosomal enzyme stability and trafficking.", "mechanism": "Deficiency or malfunction of lysosomal glycoproteins leads to substrate accumulation and multi-system disease.", "protein": "Lysosomal enzymes", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "high", "disease": "Mitochondrial disorders", "glycan_involvement": "Glycosylation affects mitochondrial protein import and function.", "mechanism": "Defective glycoproteins in mitochondrial oxidative phosphorylation impair energy production.", "protein": "Mitochondrial proteins", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Pyruvate metabolism disorders", "glycan_involvement": "Glycosylation modulates enzyme activity and stability.", "mechanism": "Mutations in glycoprotein subunits disrupt pyruvate metabolism, leading to lactic acidosis and neurological symptoms.", "protein": "Pyruvate dehydrogenase complex", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Thiamine transport/metabolism disorders", "glycan_involvement": "Glycosylation required for proper transporter localization.", "mechanism": "Defective glycoprotein transporters impair thiamine uptake, affecting energy metabolism.", "protein": "Thiamine transporter", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Organic acidurias", "glycan_involvement": "Glycosylation influences enzyme folding and activity.", "mechanism": "Deficient glycoprotein enzymes cause accumulation of toxic organic acids.", "protein": "Organic acid metabolism enzymes", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Urea cycle defects", "glycan_involvement": "Glycosylation necessary for enzyme stability.", "mechanism": "Glycoprotein enzyme defects lead to hyperammonemia and neurological symptoms.", "protein": "Urea cycle enzymes", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Peroxisomal disorders", "glycan_involvement": "Glycosylation required for enzyme targeting to peroxisomes.", "mechanism": "Defective glycoproteins disrupt peroxisomal metabolism, causing multi-organ disease.", "protein": "Peroxisomal enzymes", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "high", "disease": "Lysosomal storage diseases (LSDs)", "glycan_involvement": "Glycosylation patterns affect uptake and efficacy of therapeutic enzymes.", "mechanism": "Enzyme replacement therapy uses recombinant glycoproteins to restore lysosomal function.", "protein": "Complex molecule metabolism enzymes", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12552833" }, { "confidence": "medium", "disease": "Neurological comorbidities (seizures, dystonia)", "glycan_involvement": "Glycosylation modulates transporter function and cell surface expression.", "mechanism": "Defective glycoprotein transporters contribute to neurological symptoms in IMDs.", "protein": "Transport proteins (general)", "relationship_type": "causal", "source_pmcid": "PMC12552833" }, { "confidence": "high", "disease": "Lysosomal storage diseases (LSDs)", "glycan_involvement": "Mannose-6-phosphate glycan modification is critical for lysosomal targeting.", "mechanism": "Recombinant glycoproteins are used to treat LSDs by supplementing deficient enzymes.", "protein": "Enzyme replacement therapy targets", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12552833" }, { "confidence": "high", "disease": "Post-infection autoimmunity (A. baumannii)", "glycan_involvement": "No direct glycosylation involvement for OmpA; risk is due to peptide mimicry.", "mechanism": "Epitope mimicry between OmpA peptides and human proteins may trigger autoreactive immune responses in susceptible individuals.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "high", "disease": "Vaccine-induced autoimmunity", "glycan_involvement": "No direct glycosylation involvement for OmpA; risk is due to peptide mimicry.", "mechanism": "Vaccination with OmpA or OmpA DNA vaccine may elicit antibodies or T-cell responses cross-reactive with human proteins (e.g., Isthmin-1, RSBN1L), leading to autoimmunity.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "Isthmin-1 is a secreted glycoprotein; glycosylation may affect antigenicity and immune accessibility.", "mechanism": "Antibodies against OmpA peptide LSLARANS may cross-react with Isthmin-1, a secreted glycoprotein, potentially disrupting its anti-angiogenic and metabolic functions.", "protein": "Isthmin-1", "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "medium", "disease": "Endothelial cell apoptosis", "glycan_involvement": "Glycosylation may modulate Isthmin-1\u2019s extracellular function and immune recognition.", "mechanism": "Autoantibodies against Isthmin-1 (induced by OmpA mimicry) may block its anti-angiogenic function, affecting endothelial cell survival.", "protein": "Isthmin-1", "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "low", "disease": "Metabolic syndrome/diabetes risk", "glycan_involvement": "Glycosylation may influence secretion and function.", "mechanism": "Disruption of Isthmin-1 by cross-reactive antibodies may impair glucose uptake and lipid metabolism.", "protein": "Isthmin-1", "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "No glycosylation at the epitope site; antigenicity due to peptide sequence.", "mechanism": "OmpA peptide TKNYDSKI may induce antibodies or CTL responses cross-reactive with RSBN1L, potentially leading to nuclear autoimmunity.", "protein": "Lysine-specific demethylase RSBN1L", "protein_enriched": { "function": "Lysine-specific demethylase that specifically demethylates methylated lysine residues of proteins", "gene_name": "RSBN1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PCB5" }, "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "No glycosylation at the epitope site.", "mechanism": "OmpA peptide GQEAAAPA may induce cross-reactive immune responses targeting SMUBP-2.", "protein": "DNA-binding protein SMUBP-2", "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "Not specified.", "mechanism": "OmpA peptide LSLARANS shares similarity with epitopes in Myosin-9/11, potentially leading to cross-reactive autoimmunity.", "protein": "Myosin-9/Myosin-11", "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "Not specified.", "mechanism": "OmpA peptide GQEAAAPA may induce T-cell responses cross-reactive with ELL.", "protein": "RNA polymerase II elongation factor ELL", "protein_enriched": { "function": "Transcriptional regulator required for outer hair cells (OHC) maturation and, consequently, for hearing", "gene_name": "IKZF2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9UKS7" }, "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "Not specified.", "mechanism": "OmpA peptide GQEAAAPA may induce T-cell responses cross-reactive with this protein.", "protein": "Alpha/beta hydrolase domain-containing protein 14B", "protein_enriched": { "function": "Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed", "gene_name": "ABHD12", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G64527OM", "G70101JE", "G82463GQ", "G83633GK", "G49108TO" ], "uniprot_id": "Q8N2K0" }, "relationship_type": "causal", "source_pmcid": "PMC12553208" }, { "confidence": "high", "disease": "Emery-Dreifuss muscular dystrophy 5 (EDMD5)", "glycan_involvement": "Nesprin-2 is a glycoprotein; glycosylation may affect its stability and localization, but specific glycan changes not detailed.", "mechanism": "Pathogenic variants in SYNE2 gene encoding nesprin-2 disrupt the LINC complex, impairing nuclear-cytoskeletal connections in muscle cells.", "protein": "Nesprin-2", "protein_enriched": { "function": "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucle", "gene_name": "SYNE2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G90659AW", "G02815KT" ], "uniprot_id": "Q8WXH0" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "high", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "Emerin is a glycoprotein; glycosylation may influence nuclear envelope interactions.", "mechanism": "Mutations in EMD gene encoding emerin disrupt nuclear envelope integrity, leading to EDMD.", "protein": "Emerin", "protein_enriched": { "function": "Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-caten", "gene_name": "EMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G40834TG" ], "uniprot_id": "P50402" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "high", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "Lamin A is glycosylated; glycosylation may modulate nuclear envelope properties.", "mechanism": "LMNA gene mutations affect lamin A, compromising nuclear structure and muscle function.", "protein": "Lamin A", "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "Nesprin-1 is a glycoprotein; glycosylation may affect its function.", "mechanism": "SYNE1 gene mutations disrupt nesprin-1, affecting LINC complex and muscle cell integrity.", "protein": "Nesprin-1", "protein_enriched": { "function": "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucle", "gene_name": "SYNE1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q8NF91" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "TMEM43 is a glycoprotein; glycosylation may affect membrane localization.", "mechanism": "TMEM43 mutations disrupt nuclear envelope structure.", "protein": "Transmembrane protein 43 (TMEM43)", "protein_enriched": { "function": "May have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. Required for retaining emerin at the inner nuclear membrane (By simi", "gene_name": "TMEM43", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9BTV4" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "SUN1 is a glycoprotein; glycosylation may influence nuclear envelope interactions.", "mechanism": "SUN1 mutations affect LINC complex, impairing nuclear-cytoskeletal coupling.", "protein": "SUN domain-containing protein 1", "protein_enriched": { "function": "As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions establish", "gene_name": "SUN2", "glycan_count": 15, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO", "G02815KT", "G05724UK", "G06110VR", "G23719VF", "G31852PQ", "G39188ZX", "G41247ZX", "G49874UX", "G62765YT", "G64527OM", "G68490OW", "G80920RR", "G92050GC" ], "uniprot_id": "Q9UH99" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Emery-Dreifuss muscular dystrophy", "glycan_involvement": "SUN2 is a glycoprotein; glycosylation may influence function.", "mechanism": "SUN2 mutations disrupt LINC complex function.", "protein": "SUN domain-containing protein 2", "protein_enriched": { "function": "As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton (PubMed:18039933, PubMed:18396275). The nucleo", "gene_name": "SUN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94901" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Glycosylation may affect nesprin-2 stability in cardiac muscle.", "mechanism": "SYNE2 mutations can cause severe dilated cardiomyopathy via nuclear envelope dysfunction.", "protein": "Nesprin-2", "protein_enriched": { "function": "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucle", "gene_name": "SYNE2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G90659AW", "G02815KT" ], "uniprot_id": "Q8WXH0" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "No direct glycan involvement in transaminase elevation.", "mechanism": "Muscle breakdown in EDMD5 (nesprin-2 defect) leads to elevated AST/ALT (transaminitis) of muscle origin.", "protein": "Nesprin-2", "protein_enriched": { "function": "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucle", "gene_name": "SYNE2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G90659AW", "G02815KT" ], "uniprot_id": "Q8WXH0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12553279" }, { "confidence": "medium", "disease": "Myopathy", "glycan_involvement": "Glycosylation may affect nesprin-2 function in muscle cells.", "mechanism": "SYNE2 mutations cause myopathy via impaired nuclear-cytoskeletal connections.", "protein": "Nesprin-2", "protein_enriched": { "function": "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucle", "gene_name": "SYNE2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G90659AW", "G02815KT" ], "uniprot_id": "Q8WXH0" }, "relationship_type": "causal", "source_pmcid": "PMC12553279" }, { "confidence": "high", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation modulates stability and activity.", "mechanism": "Upregulated in BSS; drives coagulation dysfunction and correlates with syndrome severity and reduced cardiac function.", "protein": "F2 (Prothrombin)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12554561" }, { "confidence": "high", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Elevated in BSS; contributes to hypercoagulability and is responsive to TCM intervention.", "protein": "F8 (Coagulation factor VIII)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12554561" }, { "confidence": "high", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation affects plasma half-life and activity.", "mechanism": "Upregulated in BSS; associated with increased BSS score and impaired cardiac function.", "protein": "F9 (Coagulation factor IX)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12554561" }, { "confidence": "high", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation influences complement activation and immune interactions.", "mechanism": "Central in complement activation; correlates with cardiac function and syndrome severity.", "protein": "C3 (Complement C3)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12554561" }, { "confidence": "high", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N- and O-glycosylation regulate cell adhesion and matrix interactions.", "mechanism": "Altered in BSS; involved in ECM remodeling and fibrosis; upregulated post-TCM intervention.", "protein": "FN1 (Fibronectin)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12554561" }, { "confidence": "medium", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Downregulated in BSS; impairs B cell receptor signaling and immune regulation.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12554561" }, { "confidence": "medium", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation required for ligand binding and signaling.", "mechanism": "Downregulated in BSS; affects B cell signaling and immune homeostasis.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12554561" }, { "confidence": "medium", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation affects BCR assembly and signaling.", "mechanism": "Downregulated in BSS; disrupts BCR complex and immune balance.", "protein": "CD79A", "protein_enriched": { "function": "Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk", "gene_name": "CSN3", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "P02670" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12554561" }, { "confidence": "medium", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation modulates receptor stability.", "mechanism": "Downregulated in BSS; impairs BCR signaling and immune response.", "protein": "CD79B", "protein_enriched": { "function": "Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking t", "gene_name": "CD79B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P40259" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12554561" }, { "confidence": "medium", "disease": "Blood Stasis Syndrome (BSS) in IHF", "glycan_involvement": "N-glycosylation influences ligand binding and immune modulation.", "mechanism": "Reduced in BSS; loss impairs complement-B cell coupling and anti-inflammatory regulation.", "protein": "CR2 (Complement receptor 2)", "protein_enriched": { "function": "Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1 (PubMed:1849076, PubMed:21527715, PubMed:7753047). When C3d is bound to antigens, attaches to C3d on B-cel", "gene_name": "CR2", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G80920RR", "G41071NU", "G87661QW", "G62765YT", "G93910IH" ], "uniprot_id": "P20023" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12554561" }, { "confidence": "high", "disease": "Walker-Warburg Syndrome (WWS)", "glycan_involvement": "Defective O-glycosylation (matriglycan) on \u03b1-DG", "mechanism": "Loss of functional glycosylation on \u03b1-DG impairs extracellular matrix binding, leading to disease.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "Muscle-Eye-Brain (MEB) disease", "glycan_involvement": "Loss of matriglycan O-glycan structure", "mechanism": "Impaired glycosylation of \u03b1-DG disrupts its scaffold function for ECM binding.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "Limb-Girdle Muscular Dystrophy type 2P", "glycan_involvement": "Impaired O-glycosylation", "mechanism": "Defective glycosylation of \u03b1-DG reduces ECM interaction, causing muscle pathology.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "secondary dystroglycanopathies", "glycan_involvement": "Defective O-glycosylation (matriglycan)", "mechanism": "Mutations in glycosyltransferases lead to loss of \u03b1-DG functional glycans.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "secondary dystroglycanopathies", "glycan_involvement": "FKRP is required for proper matriglycan synthesis on \u03b1-DG", "mechanism": "FKRP mutations cause protein misfolding and impaired glycosylation of \u03b1-DG.", "protein": "FKRP (Fukutin-related protein)", "protein_enriched": { "function": "Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1 (By similarity)", "gene_name": "CAB39L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H9S4" }, "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "secondary dystroglycanopathies", "glycan_involvement": "Catalyzes matriglycan extension on \u03b1-DG", "mechanism": "LARGE1 is essential for matriglycan synthesis; its dysfunction leads to loss of \u03b1-DG glycosylation.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "Lassa virus infection", "glycan_involvement": "Matriglycan O-glycan is viral entry receptor", "mechanism": "Lassa virus binds to matriglycan on \u03b1-DG to enter host cells.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal (host factor)", "source_pmcid": "PMC12554582" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is glycosylated; glycosylation may affect stability and interactions with ECM.", "mechanism": "Loss of dystrophin destabilizes muscle membrane, leading to progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12557544" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Laminin is heavily glycosylated, mediating cell-ECM adhesion.", "mechanism": "Laminin is part of the dystrophin-glycoprotein complex; its interaction with dystrophin is disrupted in DMD.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12557544" }, { "confidence": "high", "disease": "Cardiac injury in DMD", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects stability and detection.", "mechanism": "IgG entry into cardiomyocytes indicates membrane leakiness and injury.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Not a glycoprotein; included for context.", "mechanism": "Elevated serum CK-MM reflects muscle membrane damage.", "protein": "Creatine kinase MM", "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Directly detects glycan modifications on muscle cell surfaces.", "mechanism": "WGA binds to N-acetylglucosamine/sialic acid on muscle fibers; used to assess muscle fiber integrity and regeneration.", "protein": "WGA binding sites", "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Muscle membrane damage", "glycan_involvement": "Glycosylation critical for laminin function and detection.", "mechanism": "Laminin staining used to assess membrane integrity in muscle histology.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Cardiac injury in DMD", "glycan_involvement": "Glycosylation may modulate dystrophin-ECM interactions.", "mechanism": "Dystrophin deficiency leads to cardiac muscle membrane instability and injury.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Cardiac injury in DMD", "glycan_involvement": "Glycosylation required for laminin localization and function.", "mechanism": "Laminin immunostaining used to delineate cardiac myocyte membranes and assess injury.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Muscle membrane damage", "glycan_involvement": "IgG glycosylation affects detection and stability.", "mechanism": "Intracellular IgG indicates compromised membrane barrier in muscle fibers.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "medium", "disease": "Muscle membrane damage", "glycan_involvement": "Direct detection of glycan changes on muscle membranes.", "mechanism": "WGA staining highlights glycan-rich regions, indicating membrane remodeling/regeneration.", "protein": "WGA binding sites", "relationship_type": "biomarker", "source_pmcid": "PMC12557544" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Lower fucosylation and galactosylation, higher agalactosylation of IgG N-glycans predict IS risk.", "mechanism": "Altered IgG N-glycosylation patterns (decreased fucosylation and galactosylation, increased agalactosylation) are associated with increased long-term risk of IS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Reduced core fucose on IgG-Fc increases Fc\u03b3RIIIA binding and inflammatory cytokine production.", "mechanism": "Decreased fucosylation enhances IgG pro-inflammatory activity via increased ADCC, contributing to IS pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Terminal galactose loss on IgG N-glycans increases pro-inflammatory complement activation.", "mechanism": "Decreased galactosylation (increased agalactosylation) exposes GlcNAc residues, activating lectin complement pathway and promoting inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Increased fucosylation and galactosylation reduce IgG pro-inflammatory effector functions.", "mechanism": "Higher fucosylation and galactosylation of IgG N-glycans are protective against IS development.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Quantitative changes in GP1, GP5, GP7 in serum IgG N-glycans predict IS occurrence.", "mechanism": "Specific IgG N-glycan peaks (GP1, GP5, GP7) serve as predictive biomarkers for IS risk in a glycan-based model.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "medium", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Lower GP5 levels linked to increased IS risk and inflammation.", "mechanism": "GP5 (agalactosylated/high-mannose glycan) is inversely associated with IS risk and may modulate inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "medium", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Certain IgG N-glycan peaks (e.g., GP19, GP24) positively correlate with hs-CRP and MMP-9.", "mechanism": "IgG N-glycan features correlate with circulating inflammatory cytokines (hs-CRP, TNF-\u03b1, MMP-9), linking glycosylation to inflammation in IS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Preclinical serum IgG N-glycan profiling identifies individuals at high IS risk.", "mechanism": "IgG N-glycosylation fingerprint enables early risk stratification for IS before clinical onset.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "medium", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Diet and exercise can beneficially alter IgG glycosylation toward anti-inflammatory profiles.", "mechanism": "Lifestyle interventions that modulate IgG N-glycosylation (increase galactosylation/fucosylation) may reduce IS risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Serum-based HILIC-UPLC IgG N-glycan analysis is feasible for clinical screening.", "mechanism": "IgG N-glycosylation profiling offers a non-invasive, robust method for IS risk prediction.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12557912" }, { "confidence": "high", "disease": "Essential Tremor (ET)", "glycan_involvement": "Binds hyaluronan (glycosaminoglycan); glycan interactions may affect neurotransmitter regulation.", "mechanism": "Increased HABP4 levels are causally associated with higher ET risk, possibly via GABA dysfunction and amino acid metabolism.", "protein": "Hyaluronan Binding Protein 4 (HABP4)", "protein_enriched": { "function": "Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalc", "gene_name": "CTRC", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99895" }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "high", "disease": "Essential Tremor (ET)", "glycan_involvement": "Catalyzes glycosylation of alpha-dystroglycan; abnormal glycosylation linked to neurodegeneration.", "mechanism": "Higher LARGE levels increase ET risk; involved in glycosphingolipid sugar chain synthesis and brain development.", "protein": "LARGE xylosyl- and glucuronyltransferase (LARGE)", "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "high", "disease": "Essential Tremor (ET)", "glycan_involvement": "No direct glycosylation, but may influence glycoprotein function via copper homeostasis.", "mechanism": "Higher ATOX1 levels decrease ET risk; maintains copper and redox homeostasis, protects against oxidative stress.", "protein": "Antioxidant 1 Copper Chaperone (ATOX1)", "protein_enriched": { "function": "Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense", "gene_name": "ATOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00244" }, "relationship_type": "protective/therapeutic_target/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "medium", "disease": "Essential Tremor (ET)", "glycan_involvement": "Heavily glycosylated; glycosylation affects cell signaling and neuroprotection.", "mechanism": "Lower GPNMB levels associated with higher ET risk; may modulate neuroinflammation.", "protein": "Glycoprotein NMB (GPNMB)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "medium", "disease": "Essential Tremor (ET)", "glycan_involvement": "Glycosylation may modulate enzyme stability and activity.", "mechanism": "Higher levels associated with increased ET risk; may affect pH regulation in neurons.", "protein": "Carbonic Anhydrase 3", "protein_enriched": { "function": "Reversible hydration of carbon dioxide", "gene_name": "Ca3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P16015" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "medium", "disease": "Essential Tremor (ET)", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Lower CBR3 levels associated with higher ET risk; involved in detoxification and oxidative stress response.", "protein": "Carbonyl Reductase 3 (CBR3)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy", "glycan_involvement": "Defective O-glycosylation of alpha-dystroglycan impairs muscle and brain function.", "mechanism": "Mutations in LARGE cause abnormal glycosylation of alpha-dystroglycan, leading to muscular and CNS symptoms.", "protein": "LARGE xylosyl- and glucuronyltransferase (LARGE)", "relationship_type": "causal", "source_pmcid": "PMC12558214" }, { "confidence": "medium", "disease": "Neurodegenerative Disorders", "glycan_involvement": "Indirect; copper homeostasis affects glycoprotein function.", "mechanism": "ATOX1 protects neurons from oxidative stress and maintains copper homeostasis.", "protein": "Antioxidant 1 Copper Chaperone (ATOX1)", "protein_enriched": { "function": "Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense", "gene_name": "ATOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00244" }, "relationship_type": "protective", "source_pmcid": "PMC12558214" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Binds hyaluronan; glycan interactions affect cell signaling.", "mechanism": "Altered HABP4 expression and glycan interactions modulate tumor suppressor/oncoprotein functions.", "protein": "Hyaluronan Binding Protein 4 (HABP4)", "protein_enriched": { "function": "Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalc", "gene_name": "CTRC", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q99895" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "low", "disease": "Metabolic Diseases", "glycan_involvement": "Indirect; copper-dependent glycoproteins involved in metabolism.", "mechanism": "ATOX1 implicated in metabolic regulation via copper-dependent enzymes.", "protein": "Antioxidant 1 Copper Chaperone (ATOX1)", "protein_enriched": { "function": "Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense", "gene_name": "ATOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00244" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558214" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Glycosylation affects ApoE structure and function, impacting lipid binding and amyloid-beta interaction.", "mechanism": "ApoE isoforms modulate cholesterol transport and amyloid-beta clearance, influencing AD risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "LDL particles contain glycoproteins; glycosylation modulates receptor binding and clearance.", "mechanism": "Elevated LDL is associated with vascular pathology contributing to AD.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558221" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "HDL-associated glycoproteins' glycosylation influences anti-inflammatory and neuroprotective functions.", "mechanism": "Higher HDL levels facilitate amyloid-beta clearance and neuronal repair, reducing AD risk.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "VLDL glycoproteins' glycosylation affects lipid transport and metabolism.", "mechanism": "Elevated cholesteryl ester in small VLDL increases AD risk via vascular and metabolic effects.", "protein": "Very Low-Density Lipoprotein (VLDL)", "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "N-glycosylation of APP modulates its cleavage and aggregation propensity.", "mechanism": "APP processing and amyloid-beta accumulation are influenced by lipid metabolism.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "Glycosylation alters ApoE's interaction with neuronal receptors.", "mechanism": "ApoE genotype and glycosylation status correlate with cognitive decline.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558221" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of LDL-associated proteins affects plaque formation.", "mechanism": "LDL accumulation promotes vascular pathology, indirectly increasing AD risk.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "Glycosylation of HDL proteins enhances neuroprotective activity.", "mechanism": "HDL supports neuronal health and reduces cognitive decline.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates VLDL metabolism and vascular effects.", "mechanism": "VLDL promotes lipid deposition in vessels, contributing to vascular dementia.", "protein": "Very Low-Density Lipoprotein (VLDL)", "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "N-glycosylation regulates APP trafficking and cleavage.", "mechanism": "Altered APP processing leads to neurotoxic amyloid-beta accumulation.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12558221" }, { "confidence": "high", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Glycosylation of E protein affects receptor binding and infectivity.", "mechanism": "Mediates host cell attachment and penetration via receptor-mediated endocytosis.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "high", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "NS1 glycosylation is essential for secretion and immune modulation.", "mechanism": "Secreted NS1 enhances midgut infection by suppressing ROS and acting as a soluble bridge for viral attachment.", "protein": "Nonstructural protein 1 (NS1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "high", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Lectin domains recognize viral glycan structures.", "mechanism": "Facilitate viral attachment to host cells.", "protein": "C-type lectins (DC-SIGN, L-SIGN, mosGCTL-1/3/7)", "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "medium", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Binds high-mannose glycans on viral envelope.", "mechanism": "Acts as an attachment factor for viral entry.", "protein": "Mannose receptor", "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "medium", "disease": "West Nile virus infection (WNV)", "glycan_involvement": "Heparan sulfate chains interact with viral glycoproteins.", "mechanism": "Facilitates viral attachment to host cells.", "protein": "Heparan sulfate proteoglycan", "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "medium", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Potential glycosylation modulates interaction.", "mechanism": "Interacts with DENV to mediate attachment in mosquito cells.", "protein": "Prohibitin", "protein_enriched": { "function": "Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and tran", "gene_name": "PHB1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G83460ZZ" ], "uniprot_id": "P35232" }, "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "high", "disease": "Hepatitis C virus infection (HCV)", "glycan_involvement": "Glycosylation of LDLR affects viral binding.", "mechanism": "Serves as entry receptor for HCV and other flaviviruses.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "high", "disease": "Hepatitis C virus infection (HCV)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Facilitates viral entry into mammalian cells.", "protein": "Scavenger receptor class B type 1", "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "medium", "disease": "Japanese encephalitis virus infection (JEV)", "glycan_involvement": "Lectin domain binds viral glycans.", "mechanism": "Mediates viral attachment in mosquito cells.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "medium", "disease": "West Nile virus infection (WNV)", "glycan_involvement": "Glycosylation may affect receptor interaction.", "mechanism": "Facilitates WNV infection in mosquitoes in collaboration with C-type lectin.", "protein": "CD45 phosphatase homolog", "relationship_type": "causal", "source_pmcid": "PMC12558446" }, { "confidence": "high", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Complex N-glycans recognized by MAL-II and PHA-E lectins.", "mechanism": "Highly upregulated on activated B cells in HT; absent in na\u00efve/memory B cells.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "high", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Glycosylation creates unique epitopes for aptamer binding.", "mechanism": "Selective targeting enables depletion of pathogenic B cells via aptamer\u2013antibody conjugate.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12558958" }, { "confidence": "medium", "disease": "B cell lymphoma", "glycan_involvement": "Complex N-glycans facilitate detection.", "mechanism": "Expressed on malignant B cells; limited on normal B cells.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "medium", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Glycosylation detected by MAL-II and PHA-E.", "mechanism": "Overexpressed on B cells in HT; less selective than TSPAN33.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "medium", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Sialylated glycans detected by MAL-II.", "mechanism": "Upregulated on B cells in HT; also present on dendritic cells.", "protein": "SIGLEC9", "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "medium", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Glycosylation signature enables detection.", "mechanism": "Expression correlates with activated B cell burden; may monitor therapeutic response.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "pharmacodynamic biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "medium", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "Altered glycosylation linked to disease activity.", "mechanism": "Associated with pathogenic B cell activation and autoantibody production.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "causal", "source_pmcid": "PMC12558958" }, { "confidence": "low", "disease": "B cell lymphoma", "glycan_involvement": "Glycosylation detected by lectin microarray.", "mechanism": "Broadly expressed on malignant B cells.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "low", "disease": "B cell lymphoma", "glycan_involvement": "Sialylated glycan involvement.", "mechanism": "Detected on malignant B cells and dendritic cells.", "protein": "SIGLEC9", "relationship_type": "biomarker", "source_pmcid": "PMC12558958" }, { "confidence": "high", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "N-glycosylation creates aptamer-accessible epitopes.", "mechanism": "Bispecific aptamer\u2013antibody conjugate enables selective B cell depletion.", "protein": "TSPAN33", "protein_enriched": { "function": "", "gene_name": "PRSS35", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8N3Z0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12558958" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "DPM1 is essential for N-glycan biosynthesis, affecting glycoprotein maturation and function.", "mechanism": "Overexpression correlates with advanced tumor stage, poor prognosis, and altered immune infiltration.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12559490" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Targeting DPM1 may disrupt aberrant N-glycosylation in tumor cells.", "mechanism": "Potential target due to its role in glycosylation pathways and association with ferroptosis and immune evasion.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12559490" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycan biosynthesis modulates glycoprotein function in cancer cells.", "mechanism": "Promotes tumor progression via altered glycosylation, impacting cell signaling and immune microenvironment.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12559490" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "Involved in N-glycosylation of proteins.", "mechanism": "Overexpressed in tumor tissue compared to normal.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12559490" }, { "confidence": "low", "disease": "Esophageal cancer", "glycan_involvement": "Involved in N-glycosylation of proteins.", "mechanism": "Overexpressed in tumor tissue compared to normal.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12559490" }, { "confidence": "low", "disease": "Head and neck cancer", "glycan_involvement": "Involved in N-glycosylation of proteins.", "mechanism": "Overexpressed in tumor tissue compared to normal.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12559490" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-GlcNAcylation modulates protein activity and ferroptosis sensitivity.", "mechanism": "O-GlcNAcylation increases susceptibility to ferroptosis, impacting tumor cell survival.", "protein": "YAP1", "relationship_type": "causal", "source_pmcid": "PMC12559490" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-GlcNAcylation modulates protein function in cancer progression.", "mechanism": "O-GlcNAcylation increases susceptibility to ferroptosis.", "protein": "ZEB1", "protein_enriched": { "function": "Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell typ", "gene_name": "ZEB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P37275" }, "relationship_type": "causal", "source_pmcid": "PMC12559490" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-GlcNAcylation affects iron metabolism and cell death pathways.", "mechanism": "O-GlcNAcylation increases ferroptosis susceptibility.", "protein": "TFRC", "relationship_type": "causal", "source_pmcid": "PMC12559490" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation alters immune cell interactions in the tumor microenvironment.", "mechanism": "High DPM1 expression correlates with increased T helper/Th2 cells and decreased cytotoxic/pDC cells, suggesting immune evasion.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "immune_modulation", "source_pmcid": "PMC12559490" }, { "confidence": "high", "disease": "Non-bacterial thrombotic endocarditis (NBTE)", "glycan_involvement": "Aberrant glycosylation of mucins increases their procoagulant activity and interaction with platelets.", "mechanism": "Mucin-producing adenocarcinomas are strongly associated with NBTE due to their prothrombotic properties.", "protein": "Mucin (MUC1/MUC16, etc.)", "relationship_type": "causal", "source_pmcid": "PMC12560192" }, { "confidence": "high", "disease": "Metastatic lung adenocarcinoma", "glycan_involvement": "Altered glycosylation patterns are used diagnostically and may affect metastatic potential.", "mechanism": "Mucin expression is a hallmark of adenocarcinomas, including lung origin.", "protein": "Mucin (MUC1/MUC16, etc.)", "relationship_type": "biomarker", "source_pmcid": "PMC12560192" }, { "confidence": "medium", "disease": "Non-bacterial thrombotic endocarditis (NBTE)", "glycan_involvement": "Glycosylation modulates tissue factor activity and stability on the cell surface.", "mechanism": "Tumor cell expression of tissue factor promotes a hypercoagulable state, predisposing to NBTE.", "protein": "Tissue Factor", "relationship_type": "causal", "source_pmcid": "PMC12560192" }, { "confidence": "medium", "disease": "Systemic embolic events (stroke, infarcts)", "glycan_involvement": "Sialylated and O-glycosylated mucins interact with selectins and platelets.", "mechanism": "Mucin-induced platelet aggregation leads to systemic emboli in cancer patients.", "protein": "Mucin (MUC1/MUC16, etc.)", "relationship_type": "causal", "source_pmcid": "PMC12560192" }, { "confidence": "medium", "disease": "Metastatic lung adenocarcinoma", "glycan_involvement": "Glycosylation affects tissue factor's procoagulant function.", "mechanism": "Overexpression of tissue factor is common in lung adenocarcinoma and correlates with thrombosis risk.", "protein": "Tissue Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12560192" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Palmitoylation (lipid modification) at Cys244 stabilizes HDAC8, preventing lysosomal degradation.", "mechanism": "HDAC8 promotes HCC progression by enhancing cell proliferation, glycolysis, \u03b2-catenin activation, and immune escape.", "protein": "HDAC8", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:147", "gene_name": "HDAC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY41" }, "relationship_type": "causal", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Mediates S-palmitoylation (lipidation) of HDAC8, not classical glycosylation.", "mechanism": "ZDHHC12 is upregulated by palmitic acid via SMARCA4, catalyzes HDAC8 palmitoylation, and promotes HCC progression.", "protein": "ZDHHC12", "relationship_type": "causal", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Targeting palmitoylated HDAC8 disrupts its stability and oncogenic function.", "mechanism": "HDAC8 inhibition (PCI-34051 or genetic knockout) suppresses HCC progression, especially in high-palmitic acid diet models.", "protein": "HDAC8", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:147", "gene_name": "HDAC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY41" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Reflects increased palmitoylation activity in tumor cells.", "mechanism": "High ZDHHC12 expression correlates with poor prognosis and higher tumor grade in HCC.", "protein": "ZDHHC12", "relationship_type": "biomarker", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Stabilization via palmitoylation increases detectable protein levels.", "mechanism": "Elevated HDAC8 protein levels in HCC tissues, especially in aggressive subclusters.", "protein": "HDAC8", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:147", "gene_name": "HDAC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY41" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561377" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation; palmitoylation of HDAC8 interferes with HSC70 binding.", "mechanism": "HSC70 mediates lysosomal degradation of HDAC8 via recognition of KFERQ-like motif; palmitoylation blocks this process.", "protein": "HSC70", "relationship_type": "protective", "source_pmcid": "PMC12561377" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation; upstream regulator of palmitoylation pathway.", "mechanism": "SMARCA4 upregulation by palmitic acid (via Wnt/SP5) increases ZDHHC12 transcription, promoting HCC.", "protein": "SMARCA4", "protein_enriched": { "function": "ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that c", "gene_name": "SMARCA4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51532" }, "relationship_type": "causal", "source_pmcid": "PMC12561377" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)-associated HCC", "glycan_involvement": "Palmitoylation stabilizes HDAC8, enhancing its oncogenic activity.", "mechanism": "HDAC8 promotes \u03b2-catenin activation and cell proliferation in NAFLD-associated HCC.", "protein": "HDAC8", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:147", "gene_name": "HDAC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY41" }, "relationship_type": "causal", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Blocks palmitoylation of HDAC8, reducing its stability.", "mechanism": "ZDHHC12 knockout or inhibition attenuates HCC progression in high-palmitic acid diet models.", "protein": "ZDHHC12", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Loss of palmitoylation leads to increased lysosomal degradation.", "mechanism": "Mutation of HDAC8 palmitoylation site (C244S) abolishes its tumor-promoting effect.", "protein": "HDAC8", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:147", "gene_name": "HDAC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY41" }, "relationship_type": "causal", "source_pmcid": "PMC12561377" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "NT-proBNP is N-glycosylated, which affects its stability and clearance.", "mechanism": "NT-proBNP is released in response to ventricular stretch and is a standard biomarker for heart failure diagnosis.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "N-glycosylation modulates NT-proBNP half-life and immunoreactivity.", "mechanism": "Elevated NT-proBNP levels indicate cardiac stress and risk after myocardial infarction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CRP is N-glycosylated, influencing its immunological activity.", "mechanism": "CRP is an acute-phase glycoprotein elevated in inflammation and atherosclerosis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects long-term glucose control, which is a risk factor for heart failure.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy (HCM)", "glycan_involvement": "N-glycosylation affects NT-proBNP detection and function.", "mechanism": "NT-proBNP levels correlate with cardiac hypertrophy and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "N-glycosylation modulates NT-proBNP stability.", "mechanism": "NT-proBNP is elevated in DCM due to ventricular dilation and stress.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation impacts CRP's inflammatory activity.", "mechanism": "CRP is elevated in heart failure due to systemic inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Cardiovascular Death", "glycan_involvement": "N-glycosylation influences NT-proBNP's plasma levels.", "mechanism": "High NT-proBNP predicts risk of cardiovascular death.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "N-glycosylation affects CRP's function and clearance.", "mechanism": "CRP is elevated post-infarction as a marker of inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "Elevated HbA1c is associated with increased risk of atherosclerosis.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12561492" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation required for secretion and function; binds chitin/heparin via glycan-dependent domains.", "mechanism": "Elevated in plasma and CSF; reflects neuroinflammation and astrocyte activation; correlates with disease progression and cognitive decline.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates immune cell secretion and stability.", "mechanism": "Elevated levels indicate inflammation and disease activity.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Correlates with inflammatory activity and tissue remodeling.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Lupus", "glycan_involvement": "Glycosylation influences immune recognition.", "mechanism": "Elevated in autoimmune inflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Glycosylation required for cell migration and extracellular interactions.", "mechanism": "Promotes cell migration and tumor progression; secreted by macrophages.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation modulates tumor cell transformation.", "mechanism": "Elevated in tumor progression and metastasis.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Colon Cancer", "glycan_involvement": "Glycosylation affects cell adhesion and migration.", "mechanism": "Associated with cancer progression and metastasis.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Gallbladder Cancer", "glycan_involvement": "Glycosylation required for secretion and extracellular function.", "mechanism": "Elevated in cancer progression.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation modulates astrocyte and microglia activation.", "mechanism": "Elevated in neuroinflammatory response post-stroke.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation required for immune cell signaling.", "mechanism": "Elevated in neuroinflammation and disease progression.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562298" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation with sialyl-Tn/Tn antigens", "mechanism": "Aberrant glycosylation leads to overexpression of sialyl-Tn and Tn antigens on MUC1, detectable as CA15-3 in serum.", "protein": "MUC1 (CA15-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, sialyl-Tn/Tn antigens", "mechanism": "MUC1 with tumor-associated carbohydrate antigens (TACAs) is a marker for various carcinomas.", "protein": "MUC1 (CA15-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "O-glycosylation, sialyl-Tn antigen", "mechanism": "HeLa cells express sialyl-Tn antigen on surface glycoproteins, detectable by glycan-binding proteins.", "protein": "HeLa cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation, sialyl-Tn antigen", "mechanism": "LS174T cells express sialyl-Tn antigen on surface glycoproteins, serving as a marker for colorectal carcinoma.", "protein": "LS174T cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, sialylation of GalNAc", "mechanism": "Overexpression or mutation of ST6GalNAc1 leads to increased sialylation of GalNAc, producing sialyl-Tn antigen in tumors.", "protein": "ST6GalNAc1", "relationship_type": "causal", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, truncated O-glycans", "mechanism": "Mutation or altered expression of COSMC disrupts normal O-glycan biosynthesis, resulting in sialyl-Tn overexpression.", "protein": "COSMC", "protein_enriched": { "function": "Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain ", "gene_name": "ERO1A", "glycan_count": 25, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G11314AS", "G15664MX", "G20579QQ", "G25079LO", "G28681TP", "G31852PQ", "G35029YA", "G39188ZX", "G41247ZX", "G46503DX", "G57317CE", "G62765YT", "G63040RU", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "Q96HE7" }, "relationship_type": "causal", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, truncated O-glycans", "mechanism": "Defective T synthase activity leads to accumulation of Tn and sialyl-Tn antigens in cancer cells.", "protein": "Core1 \u03b23-galactosyltransferase (T synthase)", "protein_enriched": { "function": "Necessary for abscisic acid (ABA) binding on the cell membrane and activation of the ABA signaling pathway in granulocytes", "gene_name": "LANCL2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS86" }, "relationship_type": "causal", "source_pmcid": "PMC12562327" }, { "confidence": "medium", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, sialyl-Tn antigen", "mechanism": "PSM expresses sialyl-Tn antigen, used as a model for tumor glycoprotein detection.", "protein": "Porcine Stomach Mucin (PSM)", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "medium", "disease": "General carcinoma", "glycan_involvement": "O-glycosylation, \u03b1-GalNAc/sialyl-Tn", "mechanism": "BSM contains \u03b1-GalNAc and minor sialyl-Tn; epitope accessibility is affected by glycan crowding, relevant for tumor glycoprotein analysis.", "protein": "Bovine Submaxillary Mucin (BSM)", "relationship_type": "biomarker", "source_pmcid": "PMC12562327" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation, sialyl-Tn/Tn antigens", "mechanism": "Aberrant glycosylation of MUC1 exposes sialyl-Tn/Tn antigens, making it a target for glycan-specific therapeutics.", "protein": "MUC1 (CA15-3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12562327" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation affects stability and secretion; glycosylation may influence biomarker detectability.", "mechanism": "Acute-phase protein upregulated by IL-6 and neutrophil activation during appendiceal inflammation; elevated in saliva and serum.", "protein": "Leucine-rich alpha-2-glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "high", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation required for secretion and function; glycosylation state may affect assay sensitivity.", "mechanism": "Acute-phase reactant elevated in systemic inflammation; salivary CRP correlates strongly with serum CRP and appendicitis severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "Predicted N-glycosylation; may affect stability and secretion.", "mechanism": "Myokine elevated in appendicitis, reflecting neutrophil activation and immune modulation; detectable in saliva.", "protein": "Irisin (FNDC5-derived)", "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "Complicated appendicitis (perforation/abscess)", "glycan_involvement": "N-glycosylation impacts serum/saliva stability.", "mechanism": "Higher levels in perforated/complicated cases; may help distinguish severity.", "protein": "Leucine-rich alpha-2-glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Elevated in bacterial infection and appendicitis; correlates with severity.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation affects secretion and receptor binding.", "mechanism": "Proinflammatory cytokine elevated in appendicitis; may help distinguish complicated cases.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "low", "disease": "Acute appendicitis", "glycan_involvement": "N-glycosylation influences stability.", "mechanism": "Acute-phase protein elevated in early appendicitis; detectable in serum and possibly saliva.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "low", "disease": "Acute appendicitis", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Neutrophil-derived protein; not reliable in urine for appendicitis, role in saliva unclear.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "O- and N-glycosylation critical for mucosal transport and immune function.", "mechanism": "Salivary IgA used for detection of mucosal immune response in pediatric COVID-19.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Elevated in saliva and serum during pediatric sepsis; correlates with severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562487" }, { "confidence": "high", "disease": "Equine recurrent uveitis (ERU)", "glycan_involvement": "Elevated O-glycosylation detected by Jacalin binding; may regulate neutrophil effector functions.", "mechanism": "Increased abundance and O-glycosylation on neutrophil surface in ERU; mediates adhesion and migration.", "protein": "Integrin beta-2", "relationship_type": "biomarker", "source_pmcid": "PMC12562876" }, { "confidence": "medium", "disease": "Equine recurrent uveitis (ERU)", "glycan_involvement": "O-glycosylation may facilitate T cell transmigration and inflammation.", "mechanism": "Increased abundance and predicted O-glycosylation on neutrophils in ERU; interacts with CD6.", "protein": "CUB domain-containing protein 1", "protein_enriched": { "function": "Mediates apoptosis and actin stress fiber dissolution", "gene_name": "SLK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2G2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12562876" }, { "confidence": "medium", "disease": "Inflammatory mucosal diseases", "glycan_involvement": "Terminal fucose, GlcNAc, and sialylated glycans modulate receptor function.", "mechanism": "Glycan modifications regulate neutrophil migration, degranulation, and superoxide generation.", "protein": "Integrin beta-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12562876" }, { "confidence": "medium", "disease": "Autoimmune uveitis (AU)", "glycan_involvement": "O-glycosylation may enhance protein-protein interaction.", "mechanism": "CUB domain-containing protein 1-CD6 interaction facilitates T cell transmigration through RPE, leading to uveitis.", "protein": "CUB domain-containing protein 1", "protein_enriched": { "function": "Mediates apoptosis and actin stress fiber dissolution", "gene_name": "SLK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2G2" }, "relationship_type": "causal", "source_pmcid": "PMC12562876" }, { "confidence": "medium", "disease": "Autoimmune/inflammatory diseases", "glycan_involvement": "Multiple N-glycosylation sites affect function.", "mechanism": "N-glycosylation modulates receptor activation and immune signaling.", "protein": "Toll-like receptor 4", "relationship_type": "regulatory", "source_pmcid": "PMC12562876" }, { "confidence": "medium", "disease": "Retinal inflammation", "glycan_involvement": "Altered sialylation detected by lectin binding.", "mechanism": "Loss of \u03b12-3 and \u03b12-6 sialic acids in uveitic state.", "protein": "Retinal M\u00fcller glia cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12562876" }, { "confidence": "low", "disease": "Equine recurrent uveitis (ERU)", "glycan_involvement": "Core fucosylation and other glycan modifications.", "mechanism": "Granule glycoproteins expressed on surface upon activation, modulating immune response.", "protein": "Neutrophil granule glycoproteins", "relationship_type": "regulatory", "source_pmcid": "PMC12562876" }, { "confidence": "low", "disease": "Autoimmune uveitis (AU)", "glycan_involvement": "PTM (lactylation) impacts protein function.", "mechanism": "Lactylation enhances microglial inflammatory gene expression in retina.", "protein": "Yin Yang 1", "relationship_type": "causal", "source_pmcid": "PMC12562876" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may modulate interaction.", "mechanism": "CD6 interaction with CUB domain-containing protein 1 implicated in autoimmune pathogenesis.", "protein": "CD6", "relationship_type": "causal", "source_pmcid": "PMC12562876" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Core fucosylation changes on T cells and neutrophil granules.", "mechanism": "Altered core fucosylation correlates with disease severity.", "protein": "Azurophil granule glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12562876" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation of BabA increases local protein stability and may enhance adhesion.", "mechanism": "BabA mediates adhesion of H. pylori to gastric mucosa via binding to Lewis b antigen.", "protein": "BabA (Blood group binding adhesin)", "protein_enriched": { "function": "", "gene_name": "moaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZL43" }, "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Gastric mucosal disease", "glycan_involvement": "Glycosylation modulates BabA's surface shielding and stability, affecting pathogenicity.", "mechanism": "BabA binding to host glycans facilitates colonization and contributes to gastric pathology.", "protein": "BabA (Blood group binding adhesin)", "protein_enriched": { "function": "", "gene_name": "moaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZL43" }, "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation affects drug accessibility and protein conformation.", "mechanism": "BabA is a target for drug development to block bacterial adhesion.", "protein": "BabA (Blood group binding adhesin)", "protein_enriched": { "function": "", "gene_name": "moaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZL43" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563011" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-linked pseudaminic acid modification essential for function.", "mechanism": "Glycosylated flagellar protein required for motility and colonization.", "protein": "FlaA", "protein_enriched": { "function": "Required for correct functioning of cytochrome bd-I oxidase. This protein and AppX may have some functional overlap", "gene_name": "cydX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56100" }, "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "O-linked pseudaminic acid modification essential for function.", "mechanism": "Glycosylated flagellar protein required for motility and colonization.", "protein": "FlaB", "protein_enriched": { "function": "May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings", "gene_name": "dnajc5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56101" }, "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Campylobacter jejuni infection", "glycan_involvement": "N-glycosylation modulates global structure and protein-protein interactions.", "mechanism": "Efflux pump glycosylation enhances protein thermostability and bacterial fitness.", "protein": "CmeA", "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "low", "disease": "Campylobacter jejuni infection", "glycan_involvement": "Multiple N-glycosylation sites mapped; functional impact likely on stability.", "mechanism": "Glycosylation increases bacterial fitness and survival.", "protein": "Cj0843", "relationship_type": "protective", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Bacterial cell wall synthesis disorders", "glycan_involvement": "UDP-N-acetylglucosamine binding reduces RMSF and stabilizes active site.", "mechanism": "Glycan binding stabilizes enzyme conformation, essential for cell wall synthesis.", "protein": "MurA", "protein_enriched": { "function": "Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes", "gene_name": "lpdA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A9P0" }, "relationship_type": "causal", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Glycosylation state affects BabA's molecular weight and binding ability.", "mechanism": "BabA presence and glycosylation status may indicate bacterial adhesion capability.", "protein": "BabA (Blood group binding adhesin)", "protein_enriched": { "function": "", "gene_name": "moaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZL43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12563011" }, { "confidence": "medium", "disease": "Gastric mucosal disease", "glycan_involvement": "Glycan shielding alters protein surface and potential drug binding sites.", "mechanism": "Glycosylation impacts BabA's druggability and epitope accessibility.", "protein": "BabA (Blood group binding adhesin)", "protein_enriched": { "function": "", "gene_name": "moaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ZL43" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563011" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Aberrant O-glycosylation (T, sTn, sLe antigens) on MUC1 is associated with tumor aggressiveness.", "mechanism": "MUC1 overexpression and altered glycosylation correlate with poor prognosis, deeper tumor invasion, lymphovascular invasion, and metastasis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Cancer-specific glycoforms (Tn, sTn, T, sLe) enable selective targeting.", "mechanism": "MUC1's tumor-associated carbohydrate antigens (TACAs) are targets for vaccine and antibody therapies.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Altered glycosylation disrupts cell\u2013cell interactions.", "mechanism": "MUC1 promotes tumor invasion by attenuating E-cadherin-mediated cell adhesion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "MUC1 glycoforms act as ligands for H. pylori.", "mechanism": "MUC1 interacts with H. pylori CagA, upregulates Wnt\u2013\u03b2-catenin signaling, and increases cell proliferation.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12563055" }, { "confidence": "medium", "disease": "Chronic atrophic gastritis", "glycan_involvement": "Glycosylated extracellular domain acts as a decoy receptor for pathogens.", "mechanism": "MUC1 suppresses IL-1\u03b2 secretion and attenuates NLRP3 inflammasome activation, protecting against gastritis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "protective", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "VNTR length affects glycosylation pattern and antigen presentation.", "mechanism": "VNTR polymorphism (short alleles) increases susceptibility to GC and chronic gastritis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Polymorphism affects glycosylation and protein function.", "mechanism": "MUC1 rs4072037 polymorphism is associated with GC risk; G allele is protective.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "O-glycosylation (T-antigen) on MUC1 drives metastatic behavior.", "mechanism": "C1GalT1-mediated T-antigen formation on MUC1 promotes GC cell migration and invasion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12563055" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Specific glycan modification inhibits MUC1 signaling.", "mechanism": "\u03b1GlcNAc biosynthesis on MUC1 binding protein suppresses GC cell proliferation and invasion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "protective", "source_pmcid": "PMC12563055" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "MUC1 glycosylation may influence TFF2 regulation.", "mechanism": "Low MUC1 or TFF2 expression correlates with worse GC outcome; MUC1 regulates TFF2 expression.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12563055" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation shields conserved epitopes from antibody recognition.", "mechanism": "Dense glycan shield on gp120 enables immune evasion and persistent infection.", "protein": "HIV-1 Envelope Glycoprotein (gp120)", "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antibody accessibility and immune escape.", "mechanism": "ADCC-mediating antibodies target fusion peptide on HA2, inducing cytotoxicity against infected cells.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation shields receptor-binding domains.", "mechanism": "Spike protein mutations and glycan shielding enable escape from neutralizing antibodies.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Not directly specified; protein-protein mimicry.", "mechanism": "Molecular mimicry between EBNA1 and myelin proteins induces autoantibody production.", "protein": "Epstein-Barr Virus Nuclear Antigen 1 (EBNA1)", "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Immune Evasion in HSV Infection", "glycan_involvement": "Glycoprotein complex mediates Fc binding.", "mechanism": "gE/gI binds IgG Fc region, blocking FcR-mediated phagocytosis.", "protein": "Herpes Simplex Virus gE/gI Complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Altered sialylation/afucosylation impacts inflammatory signaling.", "mechanism": "Fc glycosylation modulates Fc\u03b3R engagement, influencing immune complex formation and inflammation.", "protein": "IgG Fc Region", "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever", "glycan_involvement": "IgG afucosylation increases Fc\u03b3RIIIa binding, amplifying ADE.", "mechanism": "Fc\u03b3R-mediated ADE enhances viral uptake and severity.", "protein": "Fc\u03b3 Receptors (Fc\u03b3RIIa, Fc\u03b3RIIIa, Fc\u03b3RIIb)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Guillain-Barr\u00e9 Syndrome", "glycan_involvement": "Cross-reactivity with host glycolipids/gangliosides.", "mechanism": "Molecular mimicry leads to autoantibodies against neuronal gangliosides.", "protein": "Zika Virus Envelope Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever", "glycan_involvement": "Envelope glycosylation affects antibody binding and ADE risk.", "mechanism": "Non-neutralizing antibodies facilitate ADE via Fc\u03b3Rs.", "protein": "Dengue Virus Envelope Glycoprotein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "Q6YMS4" }, "relationship_type": "causal", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "Guillain-Barr\u00e9 Syndrome", "glycan_involvement": "Glycolipid antigens targeted by cross-reactive antibodies.", "mechanism": "Autoantibodies against gangliosides detected in ZIKV-associated GBS.", "protein": "Gangliosides (neuronal membrane glycolipids)", "relationship_type": "biomarker", "source_pmcid": "PMC12563229" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "O-glycosylation increases ectodomain size and repulsive barrier.", "mechanism": "Steric repulsion by bulky, highly glycosylated ectodomain inhibits viral uptake at the cell membrane.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "O-glycosylation and sialylation contribute to size and repulsion.", "mechanism": "Highly glycosylated ectodomain creates a kinetic barrier to viral entry via steric hindrance.", "protein": "CD43", "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation increases steric hindrance.", "mechanism": "Glycosylated ectodomain contributes additively to total cell surface glycan barrier, reducing infection.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation enhances ectodomain size.", "mechanism": "Glycosylated ectodomain inhibits viral uptake by increasing steric repulsion.", "protein": "SDC1", "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "O-glycosylation increases effective size.", "mechanism": "Short, highly glycosylated ectodomain inhibits viral infection by steric exclusion at low density.", "protein": "CD164", "protein_enriched": { "function": "Sialomucin that may play a key role in hematopoiesis by facilitating the adhesion of CD34(+) cells to the stroma and by negatively regulating CD34(+)CD38(lo/-) cell proliferation. Modulates the migrat", "gene_name": "CD164", "glycan_count": 36, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G29258HY", "G48584BU", "G62765YT", "G64527OM", "G70101JE", "G80920RR", "G93910IH", "G44535PQ", "G57321FI", "G73004SD", "G53434XO", "G58001LT", "G07755XJ", "G17208MA", "G29545VG", "G31596VW", "G35541EV", "G41071NU", "G42124LM", "G44753VC", "G45504EY", "G46691LC", "G49906RN", "G49955PK", "G59626AS", "G63381RX", "G68490OW", "G70619PT", "G72787SB", "G72790NZ", "G76295SF", "G77547TA", "G85282JO", "G86182NS", "G93718GY", "G72747WU" ], "uniprot_id": "Q04900" }, "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation increases steric repulsion.", "mechanism": "Highly glycosylated ectodomain creates a physical barrier to viral entry.", "protein": "PODXL", "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Glycosylation increases steric hindrance.", "mechanism": "Glycosylated ectodomain contributes to additive glycan barrier, reducing infection.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Limited by ectodomain length.", "mechanism": "Short ectodomain, despite glycosylation, does not significantly inhibit viral infection.", "protein": "GYPC", "protein_enriched": { "function": "This protein is a minor sialoglycoprotein in human erythrocyte membranes. The blood group Gerbich antigens and receptors for Plasmodium falciparum merozoites are most likely located within the extrace", "gene_name": "GYPC", "glycan_count": 13, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G43417UB", "G53434XO", "G57317CE", "G73004SD", "G29931IJ", "G79666IR", "G01614ZM", "G09480OP", "G19399OS", "G32948PW", "G65562ZE", "G74722FL", "G81006GJ" ], "uniprot_id": "P04921" }, "relationship_type": "none/weak", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Low glycosylation insufficient for protection.", "mechanism": "Low glycosylation and/or conformation do not provide significant steric barrier.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "none/weak", "source_pmcid": "PMC12563552" }, { "confidence": "high", "disease": "Viral infection (general)", "glycan_involvement": "Both N- and O-glycosylation contribute to cumulative steric barrier.", "mechanism": "Total cell surface glycan content is inversely correlated with viral infection; effect is additive and nonspecific.", "protein": "All membrane glycoproteins (additive effect)", "relationship_type": "protective", "source_pmcid": "PMC12563552" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Glycosylation affects fetuin-A function and stability; polymorphisms alter glycosylation profile.", "mechanism": "Elevated fetuin-A levels observed in DKD; involved in insulin resistance, inflammation, and mineralization.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12563721" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Glycosylation modulates receptor interaction; rs4918 polymorphism alters O-glycosylation.", "mechanism": "High fetuin-A inhibits insulin receptor signaling, promoting insulin resistance and T2D risk.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12563721" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation status may affect calcification inhibition.", "mechanism": "Lower fetuin-A levels associated with advanced CKD and increased vascular calcification.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12563721" }, { "confidence": "high", "disease": "Vascular Calcification", "glycan_involvement": "Glycosylation required for calciprotein particle formation.", "mechanism": "Fetuin-A inhibits calcium-phosphate precipitation, preventing vascular calcification.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "protective", "source_pmcid": "PMC12563721" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Missense mutation changes O-glycosylation at position 256.", "mechanism": "rs4918 polymorphism (affecting glycosylation) associated with altered GDM risk.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "risk modifier", "source_pmcid": "PMC12563721" }, { "confidence": "medium", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "Glycosylation may influence stability and calcification inhibition.", "mechanism": "Low fetuin-A linked to increased vascular calcification and mortality in ESRD.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12563721" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Urinary and plasma NGAL levels increase with tubular injury in DKD.", "protein": "Neutrophil Gelatinase-Associated Lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC12563721" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Glycosylation essential for KIM-1 function and detection.", "mechanism": "KIM-1 upregulated in proximal tubules after injury; correlates with albuminuria and DKD progression.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12563721" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Glycosylation affects \u03b1-Klotho stability and function.", "mechanism": "Low \u03b1-Klotho levels indicate early renal dysfunction in DKD.", "protein": "\u03b1-Klotho", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12563721" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Polymorphisms alter glycosylation profile, affecting protein function.", "mechanism": "AHSG gene polymorphisms (rs4917, rs4918) modulate fetuin-A levels and DKD risk.", "protein": "Fetuin-A (\u03b12-Heremans-Schmid glycoprotein)", "relationship_type": "risk modifier", "source_pmcid": "PMC12563721" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Classified as glycosyltransferase; may affect glycosylation-related pathways.", "mechanism": "Promotes proliferation, migration, invasion, and suppresses apoptosis in ccRCC cells; high expression correlates with poor prognosis.", "protein": "TYMP", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12563792" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Mediates core2 O-GalNAc glycosylation, stabilizing mucin structure and blocking abnormal glycan\u2013receptor interactions.", "mechanism": "Suppresses proliferation, migration, invasion, and promotes apoptosis; high expression correlates with favorable prognosis.", "protein": "GCNT4", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12563792" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Involved in fucosylation, modulating glycan structures on cell surface.", "mechanism": "Promotes epithelial\u2013mesenchymal transition and angiogenesis.", "protein": "FUT3", "protein_enriched": { "function": "Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to both the subterminal N-acetyl glucosamine (GlcNAc) of type 1 chain (beta-D-Gal-(1->3)-beta-D-GlcNAc) glycolipids and ", "gene_name": "FUT3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P21217" }, "relationship_type": "causal", "source_pmcid": "PMC12563792" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Involved in N-glycan branching, affecting cell signaling and immune recognition.", "mechanism": "Enhances VEGF-mediated angiogenesis and immune evasion.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "causal", "source_pmcid": "PMC12563792" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Catalyzes sialylation of glycoproteins, impacting hypoxia signaling.", "mechanism": "Facilitates HIF-1\u03b1 accumulation and glycolytic reprogramming under hypoxia.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12563792" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "N-glycosylation of PD-L1 enhances its stability and function.", "mechanism": "N-glycosylation stabilizes PD-L1, contributing to immune evasion and immunotherapy resistance.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563792" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Involved in N-glycosylation of PD-L1.", "mechanism": "Knockout reduces PD-L1 glycosylation, enhancing T cell-mediated tumor killing.", "protein": "ALG3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563792" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Heparan sulfate 3-O-sulfotransferase activity, modulating glycan sulfation.", "mechanism": "High expression correlates with longer overall survival.", "protein": "HS3ST2", "protein_enriched": { "function": "Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a se", "gene_name": "INPP5F", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q9Y2H2" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12563792" }, { "confidence": "low", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Involved in glycosylation of cell surface molecules.", "mechanism": "Included in prognostic model; higher expression associated with increased risk.", "protein": "B4GALNT4", "relationship_type": "biomarker", "source_pmcid": "PMC12563792" }, { "confidence": "low", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "UDP-glucuronosyltransferase activity.", "mechanism": "Identified as protective in model, but expression difference not significant.", "protein": "UGT2B7", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12563792" }, { "confidence": "high", "disease": "Urinary Tract Infection (UTI)", "glycan_involvement": "FimH recognizes N-glycans with terminal mannose on host cells.", "mechanism": "FimH binds mannose residues on host glycoproteins, mediating E. coli adhesion to uroepithelium; antagonists block adhesion.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Interaction with mannosylated glycoprotein CEACAM6.", "mechanism": "FimH on AIEC binds mannosylated CEACAM6 on intestinal epithelium, promoting inflammation; antagonists reduce adhesion.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "High-mannose N-glycans on gp120 are essential for infection and immune evasion.", "mechanism": "gp120 is heavily N-glycosylated with high-mannose; targeted by mannose-binding agents to block viral entry.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Recognition of high-mannose N-glycans on gp120.", "mechanism": "DC-SIGN binds HIV gp120 high-mannose glycans, facilitating viral capture and transfer to T cells.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation with oligomannose structures mediates lectin binding.", "mechanism": "Spike protein N-glycans (oligomannose) interact with DC-SIGN/L-SIGN, enhancing viral dissemination; glycomimetics block this.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "Cystic Fibrosis Lung Infection", "glycan_involvement": "Recognition of host glycans with terminal mannose/fucose.", "mechanism": "LecB binds mannose/fucose on host glycans, promoting P. aeruginosa biofilm formation; inhibitors disrupt biofilms.", "protein": "LecB", "protein_enriched": { "function": "Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA)", "gene_name": "dapA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9I4W3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "medium", "disease": "Cystic Fibrosis Lung Infection", "glycan_involvement": "Binds to host mannosylated glycans.", "mechanism": "BC2L-A binds mannose residues, mediating Burkholderia cenocepacia adhesion; multivalent mannosides inhibit binding.", "protein": "BC2L-A", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q1B6N3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Mannose-rich GPI anchors are immunogenic.", "mechanism": "Plasmodium GPIs act as toxins and immune targets; anti-GPI antibodies neutralize pathogenic effects.", "protein": "Glycosylphosphatidylinositols (GPIs)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "medium", "disease": "Candidiasis", "glycan_involvement": "Fungal cell wall \u03b2-mannan triggers immune response.", "mechanism": "\u03b2-mannan is a major antigenic determinant; \u03b2-mannan-based vaccines elicit protective immunity.", "protein": "\u03b2-mannan", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "medium", "disease": "Amoebiasis (Entamoeba histolytica infection)", "glycan_involvement": "Surface N-glycans with \u03b1-1,2-mannose are targeted.", "mechanism": "Cyanovirin-N binds \u03b1-1,2-mannose on parasite glycoproteins, inhibiting adherence and phagocytosis.", "protein": "Gal/GalNAc adherence lectin", "protein_enriched": { "function": "", "gene_name": "adh112", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U7F6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12563808" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SORT1 is a type I membrane glycoprotein; glycosylation may affect receptor trafficking and ligand binding.", "mechanism": "SORT1 missense variant (rs141749679) increases AD risk by impairing ApoE-mediated lipid uptake and amyloid \u03b2 clearance.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "causal", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE is glycosylated; glycosylation may modulate lipid binding and receptor interactions.", "mechanism": "ApoE4 allele disrupts SORT1-FABP7 signaling, impairs lipid metabolism, and increases amyloid \u03b2 accumulation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement.", "mechanism": "FABP7 upregulation in astrocytes near amyloid plaques promotes neuroinflammation; its DHA binding is neuroprotective, AA binding is pro-inflammatory.", "protein": "FABP7", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12564076" }, { "confidence": "medium", "disease": "Sleep disturbance", "glycan_involvement": "Glycosylation may affect SORT1's cell surface expression and function.", "mechanism": "SORT1 dysfunction impairs ApoE-FABP7 axis, affecting sleep regulation via lipid and endocannabinoid signaling.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "causal", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Sleep disturbance", "glycan_involvement": "No direct glycan involvement.", "mechanism": "FABP7 regulates sleep and circadian rhythms; overexpression rescues A\u03b2-induced sleep fragmentation.", "protein": "FABP7", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12564076" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects SORL1 trafficking and APP interaction.", "mechanism": "SORL1, a VPS10P family glycoprotein, is an AD risk locus involved in amyloid precursor protein trafficking.", "protein": "SorLA (SORL1)", "protein_enriched": { "function": "Involved in tethering the chromosomes to the spindle pole and in chromosome movement. Binds to the tail domain of the KIF3A/KIF3B heterodimer to form a heterotrimeric KIF3 complex and may regulate the", "gene_name": "KIFAP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92845" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP processing and A\u03b2 generation.", "mechanism": "APP mutations and abnormal processing lead to amyloid \u03b2 plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12564076" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect PSEN1 stability and function.", "mechanism": "PSEN1 mutations alter \u03b3-secretase activity, increasing amyloid \u03b2 production.", "protein": "Presenilin 1 (PSEN1)", "relationship_type": "causal", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may regulate SORT1's ligand binding and trafficking.", "mechanism": "SORT1 mediates neuroprotective signaling via ApoE3 and FABP7, activating anti-inflammatory PPAR pathways.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "No direct glycan involvement.", "mechanism": "FABP7's dual role: AA binding promotes inflammation, DHA binding promotes neuroprotection; imbalance contributes to AD progression.", "protein": "FABP7", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12564076" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Altered N-glycosylation increases protein abundance.", "mechanism": "Upregulated in GBH-exposed kidneys, indicating renal injury.", "protein": "Alpha-2-HS-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12564323" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation modulates inflammatory response.", "mechanism": "Upregulated in response to GBH-induced nephrotoxicity.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12564323" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "N-glycosylation affects integrin-mediated cell adhesion.", "mechanism": "Activated integrin signaling promotes fibrosis and tissue repair dysregulation.", "protein": "Integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12564323" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation modulates antibody function.", "mechanism": "Upregulated in male GBH-exposed kidneys, indicating immune activation.", "protein": "Ig gamma-1 chain C", "relationship_type": "biomarker", "source_pmcid": "PMC12564323" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "Potential N-glycosylation affects protein stability.", "mechanism": "Downregulated in males, linked to impaired transcriptional regulation and immune response.", "protein": "Nucleobindin-1", "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "medium", "disease": "Kidney cancer/tumor progression", "glycan_involvement": "Indirect; transcriptional regulation of glycoproteins.", "mechanism": "Activated in GBH-exposed kidneys, promotes cell proliferation and fibrosis.", "protein": "TEAD1", "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "high", "disease": "Kidney cancer/tumor progression", "glycan_involvement": "Indirect; regulates glycoprotein expression.", "mechanism": "Upregulated, drives proliferation, resistance to apoptosis, and angiogenesis.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Indirect; regulates antioxidant glycoproteins.", "mechanism": "Activated in response to GBH-induced oxidative stress.", "protein": "NFE2L2", "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Indirect; transcriptional regulation.", "mechanism": "Upregulated, supports cell proliferation and fibrosis.", "protein": "ATF4", "protein_enriched": { "function": "Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cel", "gene_name": "ATF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P18848" }, "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "medium", "disease": "Cell migration/metastasis", "glycan_involvement": "Indirect; regulates glycoprotein genes.", "mechanism": "Upregulated, promotes aberrant gene expression and tumor cell migration.", "protein": "CREB1", "relationship_type": "causal", "source_pmcid": "PMC12564323" }, { "confidence": "high", "disease": "Acute respiratory tract infection (ARI)", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Mediates viral attachment to host cells, initiating infection.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Lower respiratory tract infection", "glycan_involvement": "Glycosylation sites contribute to immune escape and pathogenicity.", "mechanism": "Facilitates RSV entry into lower airway epithelial cells.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Severe RSV disease in infants", "glycan_involvement": "Loss or gain of glycosylation sites alters immune recognition.", "mechanism": "Genotype-specific mutations and glycosylation patterns increase virulence.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12564530" }, { "confidence": "medium", "disease": "Hospitalization due to RSV", "glycan_involvement": "Duplication regions with altered glycosylation linked to epidemic spread.", "mechanism": "Genotype ON1 and BA variants associated with increased hospitalization rates.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Acute respiratory tract infection (ARI)", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Surface-exposed, neutralizing antigen; target for vaccine development.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Severe RSV disease in infants", "glycan_involvement": "Loss of N-glycosylation at L274P associated with resistance to neutralizing antibodies.", "mechanism": "Mutations (e.g., L274P, Y280H, Y304H) and glycosylation loss linked to antibody escape.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Acute respiratory tract infection (ARI)", "glycan_involvement": "Additional glycosylation sites in duplicated regions increase antigenic variability.", "mechanism": "Duplication regions (ON1: 72 bp, BA: 60 bp) enhance immune evasion.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12564530" }, { "confidence": "medium", "disease": "Lower respiratory tract infection", "glycan_involvement": "Glycosylation site changes serve as molecular epidemiology markers.", "mechanism": "Genotype shifts (ON1/BA) tracked by G protein sequence and glycosylation patterns.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Acute respiratory tract infection (ARI)", "glycan_involvement": "Diversifying selection at glycosylation sites promotes immune escape.", "mechanism": "Selection pressure on G protein glycosylation sites drives viral evolution.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12564530" }, { "confidence": "medium", "disease": "Hospitalization due to RSV", "glycan_involvement": "Glycosylation site variability influences genotype distribution and disease burden.", "mechanism": "Equal prevalence of ON1 and BA genotypes linked to epidemic dynamics.", "protein": "G protein (attachment glycoprotein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12564530" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "O-glycosylation is essential for mucin structure and function in the glycocalyx.", "mechanism": "Loss or alteration of membrane mucins in the glycocalyx leads to impaired tear film stability and epithelial barrier dysfunction.", "protein": "Membrane mucins (mucin-like glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC12565012" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Glycosylation (including sulfide bridges) is crucial for mucin polymerization and function.", "mechanism": "Secreted mucins adsorb to the cell surface, contributing to tear film stability and ocular surface protection.", "protein": "Secreted mucins", "relationship_type": "protective", "source_pmcid": "PMC12565012" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Glycosylation status reflects glycocalyx integrity.", "mechanism": "Reduction or thinning of the glycocalyx is a marker of DED severity and epithelial distress.", "protein": "Glycocalyx structural glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12565012" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Polysaccharide chains are essential for proteoglycan function in the glycocalyx.", "mechanism": "Loss of membrane proteoglycans disrupts the glycocalyx and impairs mucosal barrier function.", "protein": "Proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12565012" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Oligosaccharide branches contribute to glycocalyx formation.", "mechanism": "Altered glycolipid glycosylation affects glycocalyx structure and cell surface adhesion.", "protein": "Glycolipids", "relationship_type": "causal", "source_pmcid": "PMC12565012" }, { "confidence": "medium", "disease": "Ocular surface inflammation", "glycan_involvement": "O-glycosylation changes under inflammatory conditions.", "mechanism": "Inflammation leads to altered mucin glycosylation and loss of microvilli, compromising epithelial health.", "protein": "Membrane mucins (mucin-like glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC12565012" }, { "confidence": "high", "disease": "Tear film instability", "glycan_involvement": "Glycosylation maintains adhesive properties of the glycocalyx.", "mechanism": "Glycocalyx disruption impairs tear film adhesion and stability.", "protein": "Glycocalyx structural glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12565012" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Artificial tears mimic or restore glycosylated structures.", "mechanism": "Restoration of mucin-like glycoproteins via artificial tears (Trimix) rebuilds the glycocalyx and improves epithelial function.", "protein": "Membrane mucins (mucin-like glycoproteins)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565012" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Steric and glycosylated properties of Trimix facilitate glycocalyx reconstruction.", "mechanism": "Trimix acts as a glycocalyx substitute, restoring the SMS layer and enabling recovery of cellular exchange functions.", "protein": "Glycocalyx structural glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565012" }, { "confidence": "medium", "disease": "Tear film instability", "glycan_involvement": "Glycosylation and polymerization are essential for mucin function.", "mechanism": "Secreted mucins stabilize the tear film and prevent epithelial desiccation.", "protein": "Secreted mucins", "relationship_type": "protective", "source_pmcid": "PMC12565012" }, { "confidence": "high", "disease": "Fungal infection (Beauveria bassiana)", "glycan_involvement": "mTOR pathway co-enriched with N-glycan biosynthesis during infection.", "mechanism": "mTOR activation in Monochamus alternatus is protective against Bb; inhibition increases beetle mortality.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565087" }, { "confidence": "high", "disease": "Fungal infection (Metarhizium anisopliae)", "glycan_involvement": "N-glycan biosynthesis pathway enriched but less linked to mTOR in Ma infection.", "mechanism": "mTOR less critical for defense against Ma; inhibition does not increase beetle mortality.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "protective", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Metarhizium anisopliae)", "glycan_involvement": "Potential glycosylation regulation of DEPTOR in mTOR signaling.", "mechanism": "Upregulated in Ma infection, indicating mTOR pathway modulation.", "protein": "DEPTOR", "relationship_type": "biomarker", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Metarhizium anisopliae)", "glycan_involvement": "Possible glycosylation affecting complex stability.", "mechanism": "Upregulated in Ma infection, involved in mTOR complex regulation.", "protein": "TBC1D7", "relationship_type": "biomarker", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Metarhizium anisopliae)", "glycan_involvement": "Likely N-glycosylated, affecting protein-protein interactions.", "mechanism": "Upregulated in Ma infection, modulates mTOR signaling.", "protein": "FNIP1", "relationship_type": "biomarker", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Beauveria bassiana)", "glycan_involvement": "Glycosylation may modulate TSC2 stability/function.", "mechanism": "Differentially expressed in Bb infection, regulates mTOR activity.", "protein": "TSC2", "protein_enriched": { "function": "Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulate", "gene_name": "TSC2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G53434XO", "G49108TO" ], "uniprot_id": "P49815" }, "relationship_type": "biomarker", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Beauveria bassiana)", "glycan_involvement": "Potential glycosylation affects translation initiation.", "mechanism": "Differential expression in Bb vs Ma infection; involved in translation regulation downstream of mTOR.", "protein": "EIF4EBP1", "relationship_type": "biomarker", "source_pmcid": "PMC12565087" }, { "confidence": "high", "disease": "Fungal infection (Metarhizium anisopliae)", "glycan_involvement": "Direct involvement in N-glycosylation of immune proteins.", "mechanism": "N-glycan biosynthesis pathway upregulated in Ma infection, linked to immune defense activation.", "protein": "N-glycan biosynthesis enzymes", "relationship_type": "causal", "source_pmcid": "PMC12565087" }, { "confidence": "medium", "disease": "Fungal infection (Beauveria bassiana)", "glycan_involvement": "Glycosylation may regulate MAPK signaling components.", "mechanism": "MAPK pathway modulated by Bb to facilitate host invasion and nutrient acquisition.", "protein": "MAPK pathway proteins", "relationship_type": "causal", "source_pmcid": "PMC12565087" }, { "confidence": "high", "disease": "Pine Wilt Disease", "glycan_involvement": "mTOR signaling integrates glycan biosynthesis pathways in host defense.", "mechanism": "Manipulation of mTOR in beetle vector can enhance biocontrol efficacy against PWD.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565087" }, { "confidence": "high", "disease": "Solid tumors (multiple types)", "glycan_involvement": "Initiates N-glycosylation; increased branching, sialylation, fucosylation in cancer cells.", "mechanism": "DPAGT1 overexpression drives aberrant N-glycan branching, promoting tumor growth and survival.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "high", "disease": "Metastatic cancer", "glycan_involvement": "Alters N-glycan structures critical for cell adhesion and migration.", "mechanism": "DPAGT1 inhibition suppresses metastasis and migration in cancer cells.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "N-glycosylation required for ADAM10 activation and surface localization.", "mechanism": "DPAGT1-mediated N-glycosylation stabilizes ADAM10, promoting HER2 ectodomain shedding and resistance.", "protein": "ADAM10", "relationship_type": "causal", "source_pmcid": "PMC12565861" }, { "confidence": "high", "disease": "Trastuzumab-resistant breast cancer", "glycan_involvement": "Reduced N-glycosylation destabilizes ADAM10, decreasing HER2 shedding.", "mechanism": "Inhibition of DPAGT1 reduces ADAM10 glycosylation, limiting HER2 cleavage and resensitizing tumors.", "protein": "ADAM10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Cancer cells depend on N-glycosylation for growth and survival.", "mechanism": "DPAGT1 inhibitors selectively kill DPAGT1-overexpressing pancreatic cancer cells.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycan biosynthesis supports oncogenic signaling.", "mechanism": "DPAGT1 inhibition impairs proliferation of prostate cancer cells.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Aberrant N-glycosylation is a cancer hallmark.", "mechanism": "Selective DPAGT1 inhibitors induce apoptosis in ovarian cancer cells.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Cancer-associated N-glycan structures are targeted.", "mechanism": "DPAGT1 inhibition leads to cell death in melanoma cells.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "low", "disease": "Inflammation-related disorders", "glycan_involvement": "N-glycosylation modulates ER stress and immune signaling.", "mechanism": "DPAGT1 inhibitors may alleviate ER stress implicated in inflammation.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects protein folding and stress responses.", "mechanism": "DPAGT1 inhibition may impact diseases associated with prolonged ER stress.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12565861" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation critical for transporter function and drug interaction.", "mechanism": "Regulates oral anticoagulant absorption and clearance, affecting efficacy and toxicity.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation affects stability and interaction with inhibitors.", "mechanism": "Targeted by DOACs (apixaban, rivaroxaban) to prevent thrombus formation.", "protein": "Factor Xa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation modulates activity and inhibitor binding.", "mechanism": "Inhibited by dabigatran to prevent clot formation.", "protein": "Thrombin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Bleeding disorders", "glycan_involvement": "Glycosylation required for coagulation factor activity.", "mechanism": "Used to reverse anticoagulant-associated bleeding.", "protein": "Prothrombin complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation affects enzyme stability and substrate specificity.", "mechanism": "Metabolizes oral anticoagulants, influencing drug-drug interactions.", "protein": "Cytochrome P450 3A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "medium", "disease": "Cancer-associated VTE", "glycan_involvement": "Glycosylation essential for anticoagulant activity.", "mechanism": "Enhanced by LMWH (enoxaparin) to inhibit Factor Xa.", "protein": "Antithrombin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Cancer-associated VTE", "glycan_involvement": "Glycosaminoglycan-protein conjugation required for function.", "mechanism": "Inhibits Factor Xa via antithrombin activation.", "protein": "Enoxaparin (LMWH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Bleeding disorders", "glycan_involvement": "Antibody glycosylation affects binding and clearance.", "mechanism": "Binds dabigatran to reverse anticoagulation in bleeding.", "protein": "Idarucizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Bleeding disorders", "glycan_involvement": "Glycosylation required for recombinant protein stability.", "mechanism": "Binds Factor Xa inhibitors to reverse anticoagulation.", "protein": "Andexanet alfa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation necessary for secretion and activity.", "mechanism": "Reduced synthesis leads to coagulopathy and bleeding risk.", "protein": "Clotting factors (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12566413" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N- and O-glycosylation modulate antibody structure, stability, and immune effector functions.", "mechanism": "BsAbs simultaneously target PD-1 and VEGF to enhance anti-tumor immunity and reduce off-target toxicity.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12567180" }, { "confidence": "medium", "disease": "Drug immunogenicity", "glycan_involvement": "O-glycosylation (O-xylosylation) at Ser468 can impact immunogenic potential.", "mechanism": "O-xylosylation on (G4S)4 linker may alter immunogenicity by creating novel glycoepitopes.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "causal", "source_pmcid": "PMC12567180" }, { "confidence": "medium", "disease": "Immune-related adverse events", "glycan_involvement": "Altered N- or O-glycosylation can modulate immune recognition.", "mechanism": "Unintended glycosylation may affect immune responses and safety profile.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "causal", "source_pmcid": "PMC12567180" }, { "confidence": "low", "disease": "Infection", "glycan_involvement": "O-xylosylation enables binding to mannose receptor (CD206), potentially modulating immune response to pathogens.", "mechanism": "O-glycosylation may influence interaction with mannose receptor, affecting immune clearance.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "protective", "source_pmcid": "PMC12567180" }, { "confidence": "medium", "disease": "Drug immunogenicity", "glycan_involvement": "O-glycosylation at linker regions.", "mechanism": "Unanticipated O-glycosylation in Fc-fusion proteins can increase immunogenicity.", "protein": "Fc-fusion protein", "relationship_type": "causal", "source_pmcid": "PMC12567180" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation at Fc region affects ADCC/CDC.", "mechanism": "IgG-based antibodies are used for cancer therapy; N-glycosylation modulates effector functions.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12567180" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycan engineering (G0F dominant) eliminates Fc effector functions.", "mechanism": "BsAbs lacking Fc effector functions (due to engineered N-glycans) reduce ADCC/CDC, minimizing off-target effects.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12567180" }, { "confidence": "medium", "disease": "Drug immunogenicity", "glycan_involvement": "O-glycosylation at linker region as a critical quality attribute.", "mechanism": "O-xylosylation status can serve as a quality attribute for product consistency and immunogenicity risk.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "biomarker", "source_pmcid": "PMC12567180" }, { "confidence": "low", "disease": "Immune-related adverse events", "glycan_involvement": "O-xylosylation enables BsAb interaction with MR.", "mechanism": "Binding of O-xylosylated BsAbs to MR may modulate immune responses.", "protein": "Mannose receptor (CD206/MRC1)", "protein_enriched": { "function": "Mediates the endocytosis of glycoproteins by macrophages. Binds both sulfated and non-sulfated polysaccharide chains", "gene_name": "MRC1", "glycan_count": 47, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G08146BT", "G22310AV", "G23863VK", "G27058EU", "G33791AF", "G35541EV", "G38663NM", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G56784JY", "G57776ZS", "G57818FI", "G62765YT", "G64394MX", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G83229XP", "G84452RH", "G86795LJ", "G87123QX", "G93718GY", "G29068FM", "G43417UB", "G04657PL", "G10019LZ", "G40834TG", "G46691LC", "G90659AW", "G06356OH", "G20312EM", "G20706XG", "G25451PN", "G37868ZX", "G48414YA", "G66163OV", "G79286RS", "G80075MS", "G81263BG", "G90093AU", "G96577RX", "G25418HZ", "G51413EV", "G82830MN" ], "uniprot_id": "P22897" }, "relationship_type": "causal", "source_pmcid": "PMC12567180" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation status does not impair antigen binding.", "mechanism": "Simultaneous targeting of PD-1 and VEGF for enhanced anti-tumor effect.", "protein": "Bispecific antibody (BsAb) with (G4S)4 linker", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12567180" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation stabilizes claudin-5 structure and junctional localization.", "mechanism": "Downregulation/disassembly of claudin-5 disrupts tight junctions, increasing BBB permeability and facilitating neuroinflammation and A\u03b2 accumulation.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects occludin trafficking and tight junction assembly.", "mechanism": "Reduced occludin expression leads to BBB breakdown and increased paracellular leakage.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for GLUT1 membrane localization and function.", "mechanism": "Decreased GLUT1 impairs glucose transport across BBB, contributing to neuronal energy deficit and AD progression.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates P-gp stability and transport activity.", "mechanism": "Reduced P-gp expression impairs A\u03b2 clearance from brain, promoting plaque formation.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences LRP1 folding and ligand binding.", "mechanism": "LRP1 mediates A\u03b2 efflux; its downregulation leads to A\u03b2 accumulation.", "protein": "LRP1", "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects PDGFR\u03b2 receptor stability and signaling.", "mechanism": "Pericyte degeneration (loss of PDGFR\u03b2) increases BBB permeability and correlates with cognitive decline.", "protein": "PDGFR\u03b2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic ", "gene_name": "PDGFRB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G48414YA", "G38663NM", "G52131KU", "G86500WE", "G49108TO" ], "uniprot_id": "P09619" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12567267" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for VE-cadherin adhesive function.", "mechanism": "Disruption of VE-cadherin-mediated adherens junctions compromises BBB integrity.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates VCAM-1 binding to integrins.", "mechanism": "Upregulated VCAM-1 promotes leukocyte adhesion and transmigration, enhancing neuroinflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Cerebral amyloid angiopathy", "glycan_involvement": "Glycosylation affects fibrinogen solubility and clot formation.", "mechanism": "A\u03b2-fibrinogen interaction alters clot structure, impairs fibrinolysis, and exacerbates vascular damage.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences AQP4 membrane targeting.", "mechanism": "Loss of astrocytic polarity and AQP4 mislocalization impairs water homeostasis and BBB function.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12567267" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "Dual binding to \u03b12,3- and \u03b12,6-linked sialic acids enables cross-species transmission.", "mechanism": "HA mediates viral entry via binding to host sialic acid receptors; multi-basic cleavage site increases pathogenicity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "high", "disease": "Severe Respiratory Syndrome", "glycan_involvement": "Glycan binding specificity determines tissue tropism and severity.", "mechanism": "HA facilitates infection of respiratory epithelium, leading to severe lung pathology.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "high", "disease": "Zoonotic Influenza", "glycan_involvement": "Switch to dual \u03b12,3/\u03b12,6 sialic acid binding.", "mechanism": "HA adaptation (186V mutation) enables infection of mammals and cross-species transmission.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "NA cleaves sialic acids, promoting viral dissemination.", "mechanism": "NA facilitates viral release and spread in host tissues.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "medium", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "Indirect; affects adaptation to host glycoprotein environment.", "mechanism": "PB2 526R mutation enhances replication and pathogenicity in mammals.", "protein": "PB2", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "medium", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "Indirect; supports efficient replication in glycosylated host tissues.", "mechanism": "PA 356R and 409N mutations increase pathogenicity in mice.", "protein": "PA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P20040" }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "medium", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "Indirect; modulates host immune response to glycosylated viral proteins.", "mechanism": "NS1 42S mutation augments interferon antagonism, increasing pathogenicity.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "medium", "disease": "Encephalitis (in quails)", "glycan_involvement": "Glycan binding specificity allows neurotropism in avian species.", "mechanism": "HA enables viral entry into brain tissue in quails.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "high", "disease": "Systemic Viral Infection", "glycan_involvement": "Broad glycan binding enables systemic spread.", "mechanism": "HA mediates infection of multiple organs (heart, liver, spleen, etc.).", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "medium", "disease": "Highly Pathogenic Avian Influenza (HPAI) H7N9", "glycan_involvement": "Indirect; may affect viral assembly in glycosylated environments.", "mechanism": "M1 30D and 156D mutations contribute to increased transmissibility.", "protein": "M1", "protein_enriched": { "function": "Plays critical roles in virus replication, from virus entry and uncoating to assembly and budding of the virus particle. M1 binding to ribonucleocapsids (RNPs) in nucleus seems to inhibit viral transc", "gene_name": "M", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03485" }, "relationship_type": "causal", "source_pmcid": "PMC12567846" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Extensive O-glycosylation in mucin-like domains affects protein folding, immune evasion, and host interaction.", "mechanism": "Mediates viral attachment to host cells via CX3CR1 and modulates host immunity.", "protein": "RSV G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12568139" }, { "confidence": "high", "disease": "RSV vaccine-enhanced disease (VED)", "glycan_involvement": "O-glycosylation shields epitopes, potentially leading to dysregulated immune responses.", "mechanism": "Fully glycosylated RSV G protein in vaccines can induce Th2-biased immune responses and lung pathology in animal models.", "protein": "RSV G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12568139" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "CCD is non-glycosylated, but adjacent O-glycosylation can mask neutralizing epitopes.", "mechanism": "Antibodies targeting the central conserved domain (CCD) block RSV G interaction with CX3CR1, reducing inflammation and viral attachment.", "protein": "RSV G glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12568139" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Reduced O-glycosylation exposes neutralizing epitopes, improving antibody response and viral clearance.", "mechanism": "Restricting O-linked glycosylation on RSV G vaccine antigen enhances immunogenicity and protective efficacy in mice.", "protein": "RSV G glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12568139" }, { "confidence": "medium", "disease": "RSV vaccine-enhanced disease (VED)", "glycan_involvement": "Limited O-glycosylation reduces risk of immunopathology.", "mechanism": "O-glycan-restricted RSV G vaccine antigens do not induce pathological lung infiltrate or Th2-skewed responses in mice.", "protein": "RSV G glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12568139" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "N-glycosylation contributes to antigen stability and immunogenicity.", "mechanism": "Current licensed vaccines use stabilized pre-F as antigen, providing protection against severe RSV disease.", "protein": "RSV F glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12568139" }, { "confidence": "medium", "disease": "Herpes Zoster", "glycan_involvement": "O-glycosylation shields or exposes key epitopes depending on cell line used for production.", "mechanism": "Altered O-glycosylation in recombinant gE vaccine exposes B cell epitopes, improving vaccine efficacy.", "protein": "Herpes Zoster glycoprotein gE", "relationship_type": "protective", "source_pmcid": "PMC12568139" }, { "confidence": "high", "disease": "Lower respiratory tract disease", "glycan_involvement": "O-glycosylation in mucin-like domains influences virulence and immune evasion.", "mechanism": "RSV G mediates viral attachment and immune modulation, contributing to disease severity.", "protein": "RSV G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12568139" }, { "confidence": "medium", "disease": "RSV infection", "glycan_involvement": "O-glycosylation by GALNT3 is critical for mucin function.", "mechanism": "Down-regulation of GALNT3 inhibits O-glycosylation of Muc10, affecting mucin function in airway protection.", "protein": "Muc10", "relationship_type": "biomarker", "source_pmcid": "PMC12568139" }, { "confidence": "medium", "disease": "RSV infection", "glycan_involvement": "Glycosylation status of RSV G affects mimicry and receptor engagement.", "mechanism": "RSV G mimics CX3CL1, binding CX3CR1 to facilitate viral attachment and immune modulation.", "protein": "CX3CL1", "relationship_type": "causal", "source_pmcid": "PMC12568139" }, { "confidence": "medium", "disease": "General autoimmunity", "glycan_involvement": "N-glycosylation at Fab region modulates immune response.", "mechanism": "Fab region N-glycosylation influences antigen binding, antibody stability, and half-life, potentially affecting autoimmunity.", "protein": "Immunoglobulin kappa constant region (IGKC)", "relationship_type": "causal", "source_pmcid": "PMC12568662" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation at Fab and CH1 domains increases in RA.", "mechanism": "Increased Fab N-glycosylation associated with disease activity and pro-inflammatory IgA2 subclass.", "protein": "Immunoglobulin heavy chain (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "N-glycosylation at Fab region.", "mechanism": "Higher prevalence of Fab N-glycans observed in patients.", "protein": "Immunoglobulin heavy chain (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "Myasthenia gravis", "glycan_involvement": "N-glycosylation at Fab region.", "mechanism": "Fab N-glycosylation linked to disease presence.", "protein": "Immunoglobulin heavy chain (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "Pemphigus vulgaris", "glycan_involvement": "N-glycosylation at Fab region.", "mechanism": "Fab N-glycosylation associated with autoimmune activity.", "protein": "Immunoglobulin heavy chain (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis", "glycan_involvement": "N-glycosylation at Fab region.", "mechanism": "Fab N-glycosylation linked to disease.", "protein": "Immunoglobulin heavy chain (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12568662" }, { "confidence": "low", "disease": "Transmissible cancer (Tasmanian devil)", "glycan_involvement": "Potential N-glycosylation sites may modulate immune response.", "mechanism": "Positive selection in IGKC may reflect adaptation to immune challenges from transmissible cancer.", "protein": "Immunoglobulin kappa constant region (IGKC)", "relationship_type": "adaptive/causal", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "General autoimmunity", "glycan_involvement": "N-glycosylation at Fab region decreases autoantigen binding.", "mechanism": "Fab glycans can reduce binding affinity for autoantigens, potentially lowering autoimmune risk.", "protein": "Immunoglobulin kappa constant region (IGKC)", "relationship_type": "protective", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "General autoimmunity", "glycan_involvement": "N-glycosylation at Fab region increases BCR signaling.", "mechanism": "Fab glycans enhance B cell receptor signaling and surface expression, possibly promoting autoimmunity.", "protein": "Immunoglobulin kappa constant region (IGKC)", "relationship_type": "causal", "source_pmcid": "PMC12568662" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation at CH1 domain and other sites.", "mechanism": "Shift to pro-inflammatory IgA2 subclass with more N-glycosylation sites correlates with increased disease activity.", "protein": "Immunoglobulin heavy chain (IgA2)", "relationship_type": "causal", "source_pmcid": "PMC12568662" }, { "confidence": "high", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Increased terminal \u03b2-galactose (Gal\u03b21-4GlcNAc) on glycoproteins enhances pathogen adhesion and virulence response.", "mechanism": "High levels of RCA 1-binding glycans in the epidermis predict susceptibility and infection intensity.", "protein": "Epidermal keratinocyte glycoproteins (RCA 1-binding)", "relationship_type": "biomarker", "source_pmcid": "PMC12568929" }, { "confidence": "high", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Surface \u03b2-galactose residues serve as pathogen receptors.", "mechanism": "Epidermal galactose facilitates Bsal invasion by acting as a ligand for pathogen attachment and triggering virulence.", "protein": "Epidermal keratinocyte glycoproteins (RCA 1-binding)", "relationship_type": "causal", "source_pmcid": "PMC12568929" }, { "confidence": "medium", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Selection against high \u03b2-galactose glycosylation phenotypes.", "mechanism": "Marker-assisted selection for low RCA 1-binding glycoprotein expression may enhance resistance in breeding programs.", "protein": "Epidermal keratinocyte glycoproteins (RCA 1-binding)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12568929" }, { "confidence": "medium", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Sulfated LacNAc structures may enhance pathogen binding.", "mechanism": "Presence of 6-sulfo LacNAc in upper epidermis is associated with susceptibility.", "protein": "6-sulfo LacNAc-modified glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12568929" }, { "confidence": "low", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Sulfated glycosaminoglycan chains may act as coreceptors.", "mechanism": "Localized in granular glands of susceptible species; may facilitate pathogen interaction.", "protein": "Keratan sulfate proteoglycans", "relationship_type": "potential causal", "source_pmcid": "PMC12568929" }, { "confidence": "low", "disease": "Chytridiomycosis (Batrachochytrium salamandrivorans infection)", "glycan_involvement": "Presence may hinder pathogen adhesion.", "mechanism": "Detected in resistant species; absence in susceptible species may reduce protection.", "protein": "Dermatan sulfate proteoglycans", "relationship_type": "protective", "source_pmcid": "PMC12568929" }, { "confidence": "low", "disease": "Chytridiomycosis (Batrachochytrium dendrobatidis infection)", "glycan_involvement": "Potential involvement of \u03b2-galactose residues.", "mechanism": "Not directly studied, but similar glycan motifs may play a role.", "protein": "Epidermal keratinocyte glycoproteins (RCA 1-binding)", "relationship_type": "unknown", "source_pmcid": "PMC12568929" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for secretion and function", "mechanism": "Elevated CSF levels linked to neuroinflammation and AD progression", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "N-glycosylation modulates stability and activity", "mechanism": "Increased expression in hypertensive rats; involved in inflammation", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation affects bradykinin release", "mechanism": "Regulates blood pressure via bradykinin release; increased in hypertension", "protein": "KNG1", "relationship_type": "causal", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences protease inhibitor activity", "mechanism": "Upregulated in AD; involved in neuroinflammation", "protein": "SERPINA3", "protein_enriched": { "function": "Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2", "gene_name": "SERPINA3", "glycan_count": 192, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05724UK", "G06110VR", "G06247RL", "G08146BT", "G08918WF", "G11115RO", "G11629QQ", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G27947YN", "G31665QC", "G34617SM", "G39188ZX", "G39595FH", "G42358LZ", "G43669FQ", "G45495MK", "G47518TP", "G48414YA", "G49739MP", "G52527GH", "G52890YB", "G53075ES", "G59626AS", "G60033FS", "G64527OM", "G66088HZ", "G69834CE", "G70232NH", "G71146HJ", "G71560PC", "G74728JK", "G75983OB", "G77582RK", "G81637OR", "G84452RH", "G86795LJ", "G89205CJ", "G93656SY", "G93860XO", "G94917XT", "G95678HJ", "G99679NM", "G49108TO", "G00273SJ", "G04854VP", "G05962QB", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G20706XG", "G23010ZW", "G23863VK", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G28681TP", "G29545VG", "G30740WO", "G31028YV", "G31986NC", "G33791AF", "G36442WJ", "G37412TK", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41882MT", "G42962KI", "G43223CG", "G44215PV", "G44753VC", "G45395BF", "G46450MZ", "G46503DX", "G46691LC", "G46902YN", "G47737VJ", "G49018RC", "G50856PC", "G51413EV", "G54010QB", "G56518TU", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59324HL", "G59536GA", "G60834IK", "G63980BQ", "G64394MX", "G66282NU", "G68490OW", "G69521XL", "G70619PT", "G70888PK", "G71463BG", "G72747WU", "G72797UR", "G72951AH", "G75418YA", "G75568BH", "G77459ND", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81263BG", "G82443XX", "G82830MN", "G83229XP", "G84467IZ", "G85269DF", "G86182NS", "G86880BF", "G89877QI", "G90386IR", "G92081HT", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G70418MS", "G88374WZ", "G07810QS", "G09700PF", "G09831WQ", "G10039CR", "G10488MI", "G11101UV", "G22572EH", "G29580WD", "G30221QT", "G31309XD", "G31852PQ", "G41044JW", "G43734MM", "G44211QA", "G45526EA", "G46665ZP", "G49755GI", "G50427EO", "G52848YE", "G56770VP", "G63040RU", "G64751KD", "G65344XH", "G66537LK", "G72309KR", "G74381CZ", "G78790NZ", "G81124ET", "G83213GG", "G84225JN", "G85144OK", "G87399DK", "G90789YQ", "G92275SC", "G92551JA", "G96577RX", "G57321FI", "G29068FM", "G43417UB", "G28622IK", "G33416PL", "G37692EO", "G39471UU", "G61256FT", "G63136LV", "G85282JO", "G85554PZ", "G94310CV", "G98129XB" ], "uniprot_id": "P01011" }, "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "N-glycosylation essential for anticoagulant function", "mechanism": "Decreased levels in hypertension; regulates coagulation and inflammation", "protein": "SERPINC1 (Antithrombin III)", "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "medium", "disease": "Idiopathic normal pressure hydrocephalus", "glycan_involvement": "O-glycosylation critical for laminin binding", "mechanism": "Downregulated in CSF; involved in BBB integrity", "protein": "DAG1", "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates lipid binding and clearance", "mechanism": "Human APOE4 allele increases AD risk; regulates complement cascade", "protein": "APOE", "relationship_type": "causal", "source_pmcid": "PMC12569167" }, { "confidence": "medium", "disease": "Blood coagulation disorders", "glycan_involvement": "N-glycosylation affects complement regulation", "mechanism": "Regulates complement activation; altered in hypertension and with atenolol treatment", "protein": "CFH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12569167" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for anti-inflammatory activity", "mechanism": "Modulates inflammation; increased with atenolol treatment", "protein": "AHSG", "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation necessary for chaperone function", "mechanism": "Prevents protein aggregation; associated with amyloid deposition", "protein": "CLU", "relationship_type": "biomarker", "source_pmcid": "PMC12569167" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Aberrant O-glycosylation (sialylation of Tn antigen) creates STn epitope on cell surface.", "mechanism": "STn expression marks a TNBC subgroup with poor prognosis, increased proliferation, and immune evasion.", "protein": "Sialyl-Tn antigen (STn)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Catalyzes O-glycosylation (sialylation) of Tn antigen to form STn.", "mechanism": "Overexpression drives STn biosynthesis, correlates with immune suppressive microenvironment.", "protein": "ST6GalNAc-I", "relationship_type": "causal", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Cell surface O-glycosylation recognized by C-type lectin receptors (CD206, CD301).", "mechanism": "Promotes M2 macrophage polarization and regulatory T cell infiltration, leading to immune evasion.", "protein": "Sialyl-Tn antigen (STn)", "relationship_type": "causal", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "O-glycosylation alters cell signaling and phenotype.", "mechanism": "STn+ TNBCs show reduced c-Myc expression and increased proliferation.", "protein": "Sialyl-Tn antigen (STn)", "relationship_type": "biomarker", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Enzyme activity increases STn glycosylation.", "mechanism": "High ST6GALNAC1 expression correlates with high TGF-\u03b2 pathway gene expression and low MYC/POU5F1.", "protein": "ST6GalNAc-I", "relationship_type": "biomarker", "source_pmcid": "PMC12569379" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Aberrant O-glycosylation (STn) impairs immune activation.", "mechanism": "STn expression promotes immune tolerance via dendritic cell immaturity and low Th1 cytokines.", "protein": "Sialyl-Tn antigen (STn)", "relationship_type": "causal", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Binds O-glycosylated STn epitope on tumor cells.", "mechanism": "Recognizes STn antigen, drives M2 macrophage polarization and immunosuppression.", "protein": "CD206 (Mannose receptor)", "relationship_type": "causal", "source_pmcid": "PMC12569379" }, { "confidence": "medium", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Binds O-glycosylated Tn/STn structures.", "mechanism": "Recognizes Tn/STn antigens, associated with poor prognosis and increased IL-10 secretion.", "protein": "CD301 (MGL)", "protein_enriched": { "function": "Plays a role in the organization of endoplasmic reticulum exit sites. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinosito", "gene_name": "SEC23IP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9Y6Y8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12569379" }, { "confidence": "medium", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Indirect; STn expression correlates with TGF-\u03b2 pathway activation.", "mechanism": "Upregulated in STn+ TNBC, promotes immunosuppressive microenvironment and reduces MYC expression.", "protein": "TGF-\u03b21/TGF-\u03b23/TGFBR2", "relationship_type": "causal", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Inverse correlation with O-glycosylation (STn) status.", "mechanism": "Reduced expression in STn+ TNBC, associated with immune evasion and altered proliferation.", "protein": "c-Myc", "protein_enriched": { "function": "Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of grow", "gene_name": "MYC", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P01106" }, "relationship_type": "biomarker", "source_pmcid": "PMC12569379" }, { "confidence": "high", "disease": "Acute Hepatitis A", "glycan_involvement": "Glycosylation of viral capsid proteins influences host cell recognition.", "mechanism": "HAV capsid glycoproteins mediate viral entry and infection of hepatocytes.", "protein": "HAV Capsid Proteins", "relationship_type": "causal", "source_pmcid": "PMC12570024" }, { "confidence": "high", "disease": "Acute Hepatitis A", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated AST reflects hepatocyte injury during acute HAV infection.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12570024" }, { "confidence": "high", "disease": "Acute Hepatitis A", "glycan_involvement": "Glycosylation modulates ALT secretion and activity.", "mechanism": "ALT elevation is a sensitive marker of liver cell damage in HAV.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12570024" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation influences CK serum stability.", "mechanism": "CK is released from damaged muscle cells during rhabdomyolysis.", "protein": "CK", "relationship_type": "biomarker", "source_pmcid": "PMC12570024" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation affects renal clearance of myoglobin.", "mechanism": "Myoglobinuria indicates muscle breakdown and risk for AKI.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12570024" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may modulate immune recognition of viral proteins.", "mechanism": "Possible direct viral invasion or immune-mediated muscle injury by HAV.", "protein": "HAV Capsid Proteins", "relationship_type": "causal", "source_pmcid": "PMC12570024" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation state may affect nephrotoxicity.", "mechanism": "Excess myoglobin from rhabdomyolysis can precipitate in renal tubules, causing AKI.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "causal", "source_pmcid": "PMC12570024" }, { "confidence": "high", "disease": "Gaucher disease", "glycan_involvement": "gpNMB is a glycoprotein; glycosylation is required for its stability and secretion.", "mechanism": "gpNMB is secreted by alternatively activated macrophages in response to lysosomal stress and correlates with disease activity and substrate accumulation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "high", "disease": "Liver disease (fibrosis/cirrhosis)", "glycan_involvement": "Glycosylation enables gpNMB secretion and function in extracellular matrix remodeling.", "mechanism": "Elevated plasma gpNMB is associated with liver fibrosis/cirrhosis in GD patients, likely reflecting macrophage activation and tissue inflammation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "high", "disease": "Pulmonary disease", "glycan_involvement": "Glycosylation is essential for gpNMB\u2019s extracellular role in tissue fibrosis.", "mechanism": "High gpNMB levels correlate with pulmonary involvement (fibrosis, hypertension) in GD, reflecting inflammatory macrophage activity.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "high", "disease": "Monoclonal gammopathy (MGUS/multiple myeloma)", "glycan_involvement": "Glycosylation supports gpNMB\u2019s stability and immune modulatory functions.", "mechanism": "gpNMB is elevated in GD patients with MGUS/myeloma, possibly reflecting chronic inflammation and B-cell activation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease (in GD)", "glycan_involvement": "Glycosylation required for secretion; not specific to neurodegeneration.", "mechanism": "gpNMB is elevated in GD patients with PD, but does not distinguish GD1/3 subtypes or idiopathic PD; reflects peripheral macrophage activation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "medium", "disease": "Idiopathic Parkinson\u2019s disease", "glycan_involvement": "Glycosylation not directly implicated in PD pathogenesis.", "mechanism": "gpNMB is not significantly elevated in idiopathic PD compared to controls; not a useful biomarker in this context.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "medium", "disease": "Niemann-Pick disease type C", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "gpNMB is elevated in plasma/CSF of NPC patients, reflecting lysosomal stress and macrophage activation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "medium", "disease": "Tay-Sachs disease", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "gpNMB is elevated in plasma/CSF of Tay-Sachs patients, reflecting lysosomal dysfunction.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "medium", "disease": "Sandhoff disease", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "gpNMB is elevated in plasma/CSF of Sandhoff patients, reflecting lysosomal dysfunction.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation required for microglial secretion.", "mechanism": "gpNMB is expressed in disease-associated microglia in AD, possibly reflecting neuroinflammation.", "protein": "gpNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12570663" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation may affect TRAIL stability and receptor binding.", "mechanism": "Serum TRAIL levels negatively correlate with peak CK-MB and BNP, antagonizing ventricular remodeling and predicting better prognosis.", "protein": "TRAIL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation status modulates DR5 affinity for TRAIL and apoptotic signaling.", "mechanism": "Upregulated DR5 in ischemic myocardium enhances apoptosis via caspase cascade, worsening injury; soluble DR5 (sDR5) predicts long-term mortality.", "protein": "DR5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12570989" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation may regulate TRAIL secretion and activity.", "mechanism": "Elevated plasma TRAIL associated with reduced mortality, possibly by inhibiting apoptosis or promoting proliferation.", "protein": "TRAIL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation affects DR5 receptor function and ligand binding.", "mechanism": "Elevated soluble DR5 correlates with deterioration of left ventricular function and increased risk of heart failure.", "protein": "DR5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences TRAIL's interaction with decoy and death receptors.", "mechanism": "TRAIL-deficient macrophages show enhanced inflammation and impaired function; exogenous TRAIL reduces plaque inflammation and macrophage content.", "protein": "TRAIL", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates DR5 signaling and cell-type specificity.", "mechanism": "DR5 activation in VSMCs and endothelial cells promotes apoptosis, plaque instability, and neointimal hyperplasia.", "protein": "DR5", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12570989" }, { "confidence": "medium", "disease": "Atrial Fibrillation (AF)", "glycan_involvement": "Glycosylation may affect TRAIL's circulatory half-life and receptor interactions.", "mechanism": "Circulating TRAIL levels decrease after AF ablation; lower levels during acute AF, increase after sinus rhythm restoration.", "protein": "TRAIL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12570989" }, { "confidence": "medium", "disease": "Atrial Fibrillation (AF)", "glycan_involvement": "Glycosylation impacts DR5 receptor function and tissue distribution.", "mechanism": "Elevated sDR5 is a risk factor for AF recurrence; abnormal DR5 expression impairs immune clearance of damaged cardiomyocytes.", "protein": "DR5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Ischemia-Reperfusion Injury", "glycan_involvement": "Glycosylation affects DR5's apoptotic signaling and therapeutic targeting.", "mechanism": "DR5 activation promotes cardiomyocyte apoptosis and neutrophil-mediated inflammation; sDR5-Fc or DR5 inhibitors reduce apoptosis and improve cardiac function.", "protein": "DR5", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12570989" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation may regulate DR5 cell-surface expression and siRNA efficacy.", "mechanism": "siRNA-mediated DR5 silencing alleviates high glucose-induced podocyte injury.", "protein": "DR5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12570989" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Linked to O-glycan biosynthesis pathway (negatively associated)", "mechanism": "Upregulated in peripheral blood; part of PANoptosis signature for diagnosis", "protein": "BAZ2B", "relationship_type": "biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Linked to O-glycan biosynthesis pathway (negatively associated)", "mechanism": "High expression associated with better survival; good diagnostic/prognostic ROC", "protein": "BAZ2B", "relationship_type": "protective/prognostic biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Negatively associated with O-glycan biosynthesis pathway", "mechanism": "Upregulated in stroke; genetic variants increase risk; part of diagnostic model", "protein": "CYP1B1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12572540" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Negatively associated with O-glycan biosynthesis pathway", "mechanism": "Upregulated in stroke; part of PANoptosis diagnostic signature", "protein": "DPYD", "relationship_type": "biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Not directly specified", "mechanism": "Upregulated in stroke; part of PANoptosis diagnostic signature", "protein": "CCPG1", "relationship_type": "biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Not directly specified", "mechanism": "High expression associated with poor survival in glioma", "protein": "MTPN", "relationship_type": "risk/prognostic biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Negatively associated with O-glycan biosynthesis pathway", "mechanism": "High expression associated with poor survival in glioma", "protein": "SCYL2", "relationship_type": "risk/prognostic biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Classical glycoprotein; glycosylation modulates immune recognition", "mechanism": "Upregulated in stroke; involved in immune cell infiltration", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Not specified", "mechanism": "Upregulated in stroke; necroptosis effector in PANoptosis", "protein": "MLKL", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Negatively associated with O-glycan biosynthesis pathway", "mechanism": "Upregulated in stroke; part of PANoptosis diagnostic signature", "protein": "TMEM55A", "relationship_type": "biomarker", "source_pmcid": "PMC12572540" }, { "confidence": "high", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "O-GlcNAcylation of desmin was assessed but not significantly altered in disease context.", "mechanism": "Increased insoluble (filamentous, phosphorylated) desmin stabilizes cardiomyocyte structure and attenuates cardiac dysfunction in mdx mice.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "protective", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "Potential for targeting post-translational modifications including O-GlcNAcylation.", "mechanism": "Upregulation of desmin may be a therapeutic strategy to mitigate cardiac symptoms in DMD.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Not specified in this article.", "mechanism": "Desmin gene mutations are associated with dilated cardiomyopathy.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "causal", "source_pmcid": "PMC12572696" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is part of a glycoprotein complex; glycosylation of complex components is critical for function.", "mechanism": "Loss of dystrophin disrupts the dystrophin-glycoprotein complex, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Osteopontin is a glycoprotein; glycosylation affects its function.", "mechanism": "Osteopontin modulates immune response and extracellular matrix remodeling, influencing DMD severity.", "protein": "Osteopontin (SPP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modifier", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "LTBP4 is a glycoprotein; glycosylation may modulate its activity.", "mechanism": "LTBP4 regulates TGF-\u03b2 bioavailability, affecting fibrosis and disease progression.", "protein": "LTBP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modifier", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "O-GlcNAcylation possible but not directly linked to disease modulation here.", "mechanism": "Upregulated \u03b1B-crystallin acts as a chaperone, stabilizing desmin filaments and protecting against stress.", "protein": "\u03b1B-crystallin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "O-GlcNAcylation possible but not directly linked to disease modulation here.", "mechanism": "Increased HSP27 stabilizes desmin filaments and protects against proteolysis.", "protein": "HSP27", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "Not specified.", "mechanism": "Reduced calpain-1 decreases desmin degradation, favoring filament stability.", "protein": "Calpain-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modifier", "source_pmcid": "PMC12572696" }, { "confidence": "medium", "disease": "DMD-associated cardiomyopathy", "glycan_involvement": "Not specified.", "mechanism": "Increased BAG3 may enhance protein quality control, preventing desmin aggregation.", "protein": "BAG3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modifier", "source_pmcid": "PMC12572696" }, { "confidence": "high", "disease": "ETEC-induced diarrhea", "glycan_involvement": "O-glycosylation critical for mucin gel formation and barrier function.", "mechanism": "MUC2 upregulation enhances mucus barrier, preventing ETEC adherence and invasion.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12573840" }, { "confidence": "high", "disease": "Goblet cell depletion", "glycan_involvement": "O-glycosylation essential for MUC2 secretion and function.", "mechanism": "Reduced MUC2 expression marks goblet cell loss and impaired barrier.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Small intestinal mucosal barrier dysfunction", "glycan_involvement": "N-glycosylation affects trafficking and stability.", "mechanism": "Upregulation promotes efflux of toxins, limiting barrier damage.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "protective", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Small intestinal mucosal barrier dysfunction", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "Increased CYP3A4 enhances detoxification of xenobiotics.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "protective", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Increased intestinal permeability", "glycan_involvement": "Glycosylation stabilizes tight junction assembly.", "mechanism": "Reduced ZO-1 expression correlates with tight junction disruption.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Increased intestinal permeability", "glycan_involvement": "Glycosylation influences paracellular barrier properties.", "mechanism": "Downregulation indicates compromised tight junctions.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Increased intestinal permeability", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Loss of Occludin weakens tight junctions, increasing permeability.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Small intestinal mucosal barrier dysfunction", "glycan_involvement": "N-glycosylation critical for adhesive function.", "mechanism": "Reduced E-cadherin disrupts adherens junctions, impairing barrier.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "low", "disease": "Impaired nutrient absorption", "glycan_involvement": "Glycosylation modulates stability and function.", "mechanism": "Reduced FABP4 expression reflects impaired fatty acid uptake.", "protein": "FABP4", "protein_enriched": { "function": "Important in genetic recombination, DNA repair, and replication. Possesses pairing and strand-transfer activity. Interacts with dda and gene 32 proteins", "gene_name": "UVSX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06727" }, "relationship_type": "biomarker", "source_pmcid": "PMC12573840" }, { "confidence": "medium", "disease": "Epithelial apoptosis", "glycan_involvement": "O-glycosylation maintains mucin structure and anti-apoptotic effect.", "mechanism": "MUC2 barrier limits bacterial contact, reducing apoptosis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12573840" }, { "confidence": "high", "disease": "Gut ischemia/reperfusion injury", "glycan_involvement": "N-glycosylation required for AIM function and receptor binding.", "mechanism": "AIM reduces eCIRP-induced pro-inflammatory cytokine production in macrophages and intestinal epithelial cells by binding TLR4 and TREM-1, inhibiting eCIRP-receptor interactions.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "protective", "source_pmcid": "PMC12574078" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for anti-inflammatory activity.", "mechanism": "AIM administration improves outcomes and reduces inflammation; AIM\u2212/\u2212 mice show increased inflammation.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "protective", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation required for DAMP scavenging.", "mechanism": "AIM binds DAMPs (S100, HMGB1, heat shock proteins) to reduce inflammation and improve outcomes.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "protective", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "N-glycosylation required for receptor interaction.", "mechanism": "AIM promotes clearance of necrotic cell debris via scavenger receptors (CD36, KIM-1).", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "protective", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "N-glycosylation may affect anti-apoptotic activity.", "mechanism": "AIM may reduce intracellular killing of S. aureus, potentially allowing bacterial persistence due to anti-apoptotic functions.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "causal", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Cardiovascular disease (atherosclerosis)", "glycan_involvement": "N-glycosylation may influence cell survival signaling.", "mechanism": "AIM perpetuates lifespan of plaque-promoting foam cells.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "causal", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Serum AIM concentration increased in SLE patients.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574078" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Serum AIM concentration increased in sepsis patients.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574078" }, { "confidence": "high", "disease": "Gut ischemia/reperfusion injury", "glycan_involvement": "N-glycosylation required for detection and function.", "mechanism": "AIM protein and mRNA levels decrease in lungs and plasma after gut I/R.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574078" }, { "confidence": "high", "disease": "Sterile inflammation (general)", "glycan_involvement": "N-glycosylation required for receptor binding and anti-inflammatory activity.", "mechanism": "AIM neutralizes DAMPs and inhibits TLR4/TREM-1 signaling.", "protein": "AIM/CD5L", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection", "gene_name": "Cd5l", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9QWK4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12574078" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "MafA 2/3 binds host glycolipids (gangliotriosylceramide GgO3, gangliotetraosylceramide GgO4) for adhesion.", "mechanism": "Surface-exposed MafA 2/3 induces bactericidal antibodies and inhibits bacterial association with human epithelial cells.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12574560" }, { "confidence": "medium", "disease": "Pelvic Inflammatory Disease", "glycan_involvement": "Glycolipid binding promotes tissue invasion.", "mechanism": "MafA 2/3-mediated adhesion facilitates mucosal colonization and ascending infection.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12574560" }, { "confidence": "medium", "disease": "Gonococcal Ophthalmia Neonatorum", "glycan_involvement": "Adhesion to glycan-rich conjunctival cells.", "mechanism": "MafA 2/3 enables colonization of ocular mucosa in neonates.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12574560" }, { "confidence": "medium", "disease": "Disseminated Gonococcal Infection (DGI)", "glycan_involvement": "Glycan-mediated interactions with host tissues.", "mechanism": "Facilitates spread to internal soft tissue sites via adhesion.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12574560" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "Antibody binding may block glycan-mediated adhesion.", "mechanism": "Antibodies against MafA 2/3 are bactericidal and block epithelial cell association.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12574560" }, { "confidence": "medium", "disease": "Gonorrhea", "glycan_involvement": "Secreted via glycoprotein pathway; may interact with host glycans.", "mechanism": "MafB acts as a toxin secreted via MafA pathway, contributing to bacterial competition and virulence.", "protein": "MafB", "relationship_type": "causal", "source_pmcid": "PMC12574560" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "Glycan-binding domain is immunogenic.", "mechanism": "MafA 2/3 is highly conserved and expressed in majority of clinical isolates; recognized by patient sera.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12574560" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "Antibody may block glycan-mediated adhesion.", "mechanism": "Rabbit anti-MafA 2/3 serum is broadly bactericidal against diverse gonococcal strains.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12574560" }, { "confidence": "medium", "disease": "Gonorrhea", "glycan_involvement": "Bacterial sialylation masks glycoprotein epitopes.", "mechanism": "Sialylation of gonococci reduces bactericidal activity of anti-MafA 2/3 antibodies.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12574560" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "Glycan-binding activity is central to vaccine efficacy.", "mechanism": "MafA 2/3 is proposed as a subunit vaccine antigen.", "protein": "MafA 2/3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12574560" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "GLUT4 is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "GLUT4 expression is upregulated in HF, indicating increased glycolysis and impaired energy metabolism.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation modulates GLUT4 membrane localization and activity.", "mechanism": "Elevated GLUT4 expression aggravates myocardial glucose homeostasis and structural damage, promoting fibrosis.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC12575102" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "CD36 is a glycoprotein; glycosylation influences fatty acid uptake.", "mechanism": "CD36 upregulation leads to toxic lipid accumulation, impairing membrane integrity and promoting apoptosis in HF.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12575102" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "No direct glycosylation; regulates glycoprotein expression (e.g., CD36, GLUT4).", "mechanism": "PPAR\u03b1 activation restores fatty acid oxidation and improves cardiac energy supply in HF.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "No direct glycosylation; regulates glycoprotein expression.", "mechanism": "RXR\u03b1 dimerizes with PPAR\u03b1 to upregulate lipid metabolism proteins, improving energy metabolism in HF.", "protein": "RXR\u03b1", "protein_enriched": { "function": "Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and", "gene_name": "RXRA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19793" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "No direct glycosylation; regulated by PPAR\u03b1/RXR\u03b1.", "mechanism": "CPT1\u03b1 upregulation enhances mitochondrial fatty acid transport and oxidation, improving cardiac energy supply.", "protein": "CPT1\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Indirect; regulates glycoprotein trafficking.", "mechanism": "AMPK\u03b1 activation stimulates GLUT4 expression and glucose uptake, supporting energy homeostasis.", "protein": "AMPK\u03b1", "protein_enriched": { "function": "Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563", "gene_name": "PRKAA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13131" }, "relationship_type": "protective", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Indirect; regulates metabolic gene expression.", "mechanism": "Sirt1 activation promotes PPAR\u03b1 signaling and fatty acid oxidation, improving energy metabolism.", "protein": "Sirt1", "relationship_type": "protective", "source_pmcid": "PMC12575102" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation is essential for GLUT4 trafficking and activity.", "mechanism": "GLUT4 expression and function are impaired in insulin resistance, affecting glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575102" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Glycosylation modulates GLUT4 function in cardiac tissue.", "mechanism": "Altered GLUT4 expression reflects impaired glucose metabolism in diabetic cardiomyopathy.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575102" }, { "confidence": "high", "disease": "All-cause mortality in T2DM", "glycan_involvement": "Direct; NA3F is a triantennary, \u03b1-1,3 core-fucosylated N-glycan structure from serum glycoproteins.", "mechanism": "Higher NA3F abundance is associated with increased mortality risk in T2DM; reflects N-glycan remodeling linked to aging, inflammation, or glycoprotein turnover.", "protein": "Serum N-glycan NA3F", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "All-cause mortality in T2DM", "glycan_involvement": "Direct; altered N-glycosylation patterns on IgG.", "mechanism": "IgG N-glycosylation profile (including NA3F) is associated with mortality risk, reflecting immune and inflammatory status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "high", "disease": "All-cause mortality in T2DM", "glycan_involvement": "ApoA1 is a glycoprotein; glycosylation may affect its function and stability.", "mechanism": "Higher ApoA1 levels are inversely associated with mortality risk; ApoA1 is the main protein of HDL, involved in lipid transport.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective", "source_pmcid": "PMC12575121" }, { "confidence": "high", "disease": "All-cause mortality in T2DM", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation may influence its stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and predicts increased mortality risk.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "high", "disease": "All-cause mortality in T2DM", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its function.", "mechanism": "Elevated hs-CRP indicates chronic inflammation and is associated with increased mortality risk.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "All-cause mortality in T2DM", "glycan_involvement": "sST2 is a glycoprotein; glycosylation may modulate its bioactivity.", "mechanism": "Higher sST2 levels are associated with increased mortality risk, reflecting inflammation and cardiac stress.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "All-cause mortality in T2DM", "glycan_involvement": "Troponin I is glycosylated; glycosylation may affect its detection and function.", "mechanism": "Elevated hs-cTnI reflects myocardial injury and is associated with increased mortality risk.", "protein": "hs-cTnI", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Direct; reflects systemic N-glycan remodeling in T2DM.", "mechanism": "NA3F abundance is associated with metabolic and inflammatory features in T2DM.", "protein": "Serum N-glycan NA3F", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may influence ApoA1's anti-atherogenic properties.", "mechanism": "Higher ApoA1 levels are associated with reduced cardiovascular risk.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective", "source_pmcid": "PMC12575121" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated hs-CRP is a marker of residual inflammatory risk and predicts cardiovascular events.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12575121" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "N-acetyl methyl groups from N-glycans on acute-phase glycoproteins", "mechanism": "Reflects systemic inflammation; mediates 14.43% of the association between healthy lifestyle and IBD risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation of acute-phase proteins; increased glycan acetylation reflects inflammation", "mechanism": "Marker of chronic inflammation, which promotes insulin resistance and diabetes risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Ischemic heart disease", "glycan_involvement": "N-glycosylation; glycan acetylation as inflammation marker", "mechanism": "Associated with cardiometabolic risk via systemic inflammation.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "N-glycosylation; composite signal from multiple glycoproteins", "mechanism": "Elevated levels indicate increased risk due to chronic inflammation.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation of acute-phase proteins", "mechanism": "Reflects low-grade inflammation contributing to COPD pathogenesis.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "N-glycosylation affects stability and function", "mechanism": "Low albumin levels indicate impaired liver function and disease progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation modulates antioxidant and anti-inflammatory properties", "mechanism": "Lower albumin associated with increased diabetes risk; reflects metabolic and inflammatory status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "N-glycosylation influences renal clearance and function", "mechanism": "Low albumin is a marker of renal dysfunction and disease severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "N-glycosylation of acute-phase proteins", "mechanism": "Elevated glycoprotein acetyls linked to increased hypertension risk via inflammation.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "N-glycosylation modulates vascular protection", "mechanism": "Low albumin levels associated with increased stroke risk; reflects vascular and inflammatory status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575140" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Hypoglycosylation at N275/N350 increases cell surface retention.", "mechanism": "Promotes immune evasion via DC-HIL/Syndecan-4 pathway and supports metastatic niche formation.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "ADAM10/17-mediated shedding generates sGPNMB; glycosylation affects shedding and function.", "mechanism": "Overexpression correlates with poor prognosis; ADC targeting shows high response rates; promotes metastasis via integrin binding and sGPNMB-mediated angiogenesis.", "protein": "GPNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "ECD glycosylation influences cell adhesion and signaling.", "mechanism": "Marks cancer stem cells and EMT; high expression correlates with poor prognosis and therapy resistance.", "protein": "GPNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Highly glycosylated OA isoform essential for osteoblast differentiation; mannosylation regulates function.", "mechanism": "Activates PI3K/Akt/mTOR pathway, promoting proliferation and migration.", "protein": "GPNMB", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "ADAM10-mediated shedding produces sGPNMB; glycosylation modulates shedding.", "mechanism": "Elevated expression drives migration/invasion via MMP activation and shapes immunosuppressive TME.", "protein": "GPNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Type I membrane glycoprotein; glycosylation status affects cell surface expression.", "mechanism": "High expression correlates with advanced stage, residual tumor, and metastasis; regulates proliferation and metabolism.", "protein": "GPNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "medium", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Glycosylation not directly specified; likely impacts stability and signaling.", "mechanism": "Overexpression drives acquired resistance to immune checkpoint inhibitors via SOX10-MITF-GPNMB axis.", "protein": "GPNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (ALS, PD)", "glycan_involvement": "S546 phosphorylation and glycosylation modulate phagocytosis and protein stability.", "mechanism": "Neuroprotective via PI3K/MEK/ERK signaling; loss impairs aSyn clearance and promotes neurodegeneration.", "protein": "GPNMB", "relationship_type": "protective/causal", "source_pmcid": "PMC12575166" }, { "confidence": "medium", "disease": "Obesity/metabolic syndrome", "glycan_involvement": "Shedding and glycosylation regulate sGPNMB release and activity.", "mechanism": "Promotes WAT lipogenesis and anti-inflammatory macrophage polarization; sGPNMB inhibits NF-\u03baB signaling.", "protein": "GPNMB", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12575166" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation influences cell surface retention and signaling.", "mechanism": "Macrophage-derived GPNMB activates fibroblasts via CD44/Serpinb2, promoting collagen deposition and ECM remodeling.", "protein": "GPNMB", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12575166" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation shields the spike protein, modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry by binding to human ACE2 receptor, initiating infection.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ligand accessibility and binding pocket conformation.", "mechanism": "Spike glycoprotein RBD is targeted by phytochemicals (betulinic acid, \u03b2-sitosterol) to block ACE2 interaction and viral entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycans may modulate drug binding and efficacy.", "mechanism": "Spike glycoprotein is targeted by antiviral drugs (ivermectin, remdesivir, favipiravir, hydroxychloroquine) to inhibit viral entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Variant-specific mutations may alter glycosylation patterns, affecting immune recognition.", "mechanism": "Spike glycoprotein variants (Alpha, Beta, Delta, Omicron) alter binding affinity for ACE2 and neutralizing antibodies, impacting infectivity and immune escape.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence phytochemical binding and steric hindrance.", "mechanism": "Phytochemicals (betulinic acid, \u03b2-sitosterol) show stable binding to spike RBD, potentially preventing viral entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12575622" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycan shield may reduce ivermectin's stable engagement.", "mechanism": "Ivermectin binds spike RBD but forms unstable complexes, suggesting limited direct efficacy.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect binding pocket accessibility.", "mechanism": "Ursolic acid binds spike RBD with moderate stability, possibly interfering with ACE2 interaction.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans mask epitopes, modulating immune recognition.", "mechanism": "Spike glycoprotein is the main antigenic target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "Spike glycoprotein presence is used for diagnostic detection of SARS-CoV-2 infection.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutations may alter glycosylation sites, impacting viral fitness.", "mechanism": "Spike glycoprotein mutations (e.g., D614G, N501Y, E484K) increase transmissibility and immune evasion.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12575622" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is a glycoprotein; glycosylation affects aggregation and clearance.", "mechanism": "Intraneuronal accumulation and impaired clearance trigger early AD pathology; associated with cognitive decline.", "protein": "Amyloid-\u03b2 (A\u03b2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12575788" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation.", "mechanism": "Hyperphosphorylation and aggregation into neurofibrillary tangles; correlates with neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "MOG is N-glycosylated; glycosylation affects immune recognition and stability.", "mechanism": "Elevated plasma MOG indicates oligodendrocyte/myelin damage, associated with cognitive decline.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect filament assembly.", "mechanism": "Increased GFAP reflects astrocyte reactivity and injury; correlates with neuroinflammation.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "NfL is glycosylated; glycosylation may affect stability and turnover.", "mechanism": "Elevated plasma NfL indicates axonal damage and neurodegeneration.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12575788" }, { "confidence": "high", "disease": "Cerebral amyloid angiopathy", "glycan_involvement": "Glycosylation influences A\u03b2 aggregation and vascular deposition.", "mechanism": "A\u03b2 deposition in vessel walls leads to vascular dysfunction and increased risk of hemorrhage.", "protein": "Amyloid-\u03b2 (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12575788" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation may affect A\u03b2 clearance by liver receptors.", "mechanism": "Liver dysfunction impairs peripheral A\u03b2 clearance, increasing brain accumulation.", "protein": "Amyloid-\u03b2 (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Aqp1 is glycosylated; glycosylation affects trafficking and function.", "mechanism": "Upregulated in response to A\u03b2; may facilitate A\u03b2 clearance and cell motility.", "protein": "Aquaporin-1 (Aqp1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Aqp4 is glycosylated; glycosylation modulates localization and stability.", "mechanism": "Loss of perivascular Aqp4 impairs glymphatic clearance of A\u03b2, promoting accumulation.", "protein": "Aquaporin-4 (Aqp4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12575788" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Aqp9 is glycosylated; glycosylation affects channel function.", "mechanism": "Downregulation impairs neuronal energy metabolism and may exacerbate A\u03b2 toxicity.", "protein": "Aquaporin-9 (Aqp9)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12575788" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Gc is a glycoprotein forming trimeric spikes on the virion surface, facilitating attachment and entry.", "mechanism": "Gc mediates viral entry and is essential for infection of host cells.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Gn is a glycoprotein; glycosylation likely aids in proper folding and function.", "mechanism": "Gn, together with Gc, forms spikes on the viral surface and is involved in attachment to host cells.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Congenital malformations in ruminants", "glycan_involvement": "Gc glycosylation may influence tropism and immune evasion.", "mechanism": "Infection during gestation leads to fetal infection and malformations; Gc is required for viral infectivity.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Abortion in ruminants", "glycan_involvement": "Glycosylation of Gc may affect host interactions.", "mechanism": "Viral infection of pregnant animals can cause abortion; Gc is essential for viral entry.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation may modulate antigenicity and antibody recognition.", "mechanism": "Gc is the major antigenic domain targeted by neutralizing antibodies.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12576038" }, { "confidence": "high", "disease": "Schmallenberg virus infection", "glycan_involvement": "Tagging does not disrupt glycoprotein function; glycosylation sites outside the tag remain functional.", "mechanism": "Nanoluciferase-tagged Gc enables sensitive detection and tracking of viral infection in vitro.", "protein": "Nanoluciferase-tagged Gc", "relationship_type": "biomarker", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Deletion removes part of the antigenic domain, possibly altering glycosylation pattern.", "mechanism": "Deletion of Gc-head does not abolish infectivity in vitro, indicating dispensability for replication.", "protein": "Gc glycoprotein (with head domain deletion)", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation may affect epitope exposure and antibody binding.", "mechanism": "Neutralizing antibodies against Gc confer protection; even truncated Gc can be neutralized.", "protein": "Gc glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation status may influence assay sensitivity.", "mechanism": "Gc is used in serological assays to detect infection or immunity.", "protein": "Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12576038" }, { "confidence": "medium", "disease": "Schmallenberg virus infection", "glycan_involvement": "Glycosylation of Gc may modulate interaction with host glycosaminoglycans.", "mechanism": "Heparan sulphate binding by Gc mediates viral entry into host cells.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12576038" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin is a glycoprotein; glycosylation is important for its stability and interaction with the dystrophin-associated glycoprotein complex.", "mechanism": "Mutations in the DMD gene lead to absent or nonfunctional dystrophin, destabilizing the sarcolemma and causing muscle fiber damage.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation may modulate residual dystrophin function and stability.", "mechanism": "In-frame mutations in the DMD gene result in partially functional dystrophin, leading to milder symptoms.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Restored dystrophin must be properly glycosylated for full function.", "mechanism": "Exon-skipping therapies aim to restore the reading frame of DMD transcripts, enabling production of functional dystrophin.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Functional dystrophin produced via readthrough must be glycosylated for stability.", "mechanism": "Premature termination codon-readthrough therapies (e.g., ataluren) target nonsense mutations to allow translation of full-length dystrophin.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation status may affect detection sensitivity in assays.", "mechanism": "Absence or reduction of dystrophin in muscle biopsy is diagnostic for DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Truncated proteins may lack glycosylation sites, affecting stability.", "mechanism": "Frameshift and nonsense mutations in DMD gene result in truncated dystrophin, leading to severe DMD phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Loss of glycosylation domains may exacerbate instability.", "mechanism": "Multi-exon deletions (e.g., exons 3\u20137) cause loss of functional dystrophin and severe DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Frameshifted proteins may lack glycosylation, reducing function.", "mechanism": "Single-nucleotide duplications (e.g., exon 30) introduce frameshifts, leading to nonfunctional dystrophin.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Altered glycosylation patterns may contribute to severity.", "mechanism": "Single-exon deletions (e.g., exon 30) can cause severe DMD despite being in-frame, indicating genotype-phenotype discordance.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Therapeutic dystrophin must be glycosylated for proper function.", "mechanism": "Gene therapy (micro-dystrophin replacement, CRISPR-Cas9) aims to restore dystrophin expression.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12576112" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "Glycosylation required for ATP7B stability and trafficking.", "mechanism": "ATP7B mutations impair copper transport, causing hepatic copper accumulation and oxidative damage.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Alagille syndrome", "glycan_involvement": "Glycosylation modulates JAG1-Notch interaction.", "mechanism": "JAG1 mutations disrupt Notch signaling, leading to bile duct paucity and multisystem defects.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Dubin-Johnson syndrome", "glycan_involvement": "Glycosylation affects ABCC2 membrane localization.", "mechanism": "ABCC2 mutations impair canalicular transport of conjugated bilirubin, causing hyperbilirubinemia.", "protein": "ABCC2", "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Progressive Familial Intrahepatic Cholestasis Type 1 (PFIC1)", "glycan_involvement": "Glycosylation influences ATP8B1 folding and function.", "mechanism": "ATP8B1 mutations disrupt phospholipid transport, leading to cholestasis and extrahepatic symptoms.", "protein": "ATP8B1", "protein_enriched": { "function": "Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity t", "gene_name": "SEC14L2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O76054" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Glycogen Storage Disease Type Ia", "glycan_involvement": "Glycosylation required for G6PC enzymatic activity.", "mechanism": "G6PC mutations impair glucose-6-phosphatase activity, causing hypoglycemia and hepatomegaly.", "protein": "G6PC", "protein_enriched": { "function": "Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production in the terminal ste", "gene_name": "G6PC1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G84452RH" ], "uniprot_id": "P35575" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Glycogen Storage Disease Type III", "glycan_involvement": "Glycosylation modulates AGL stability.", "mechanism": "AGL mutations reduce glycogen debranching, leading to abnormal glycogen accumulation in liver.", "protein": "AGL", "protein_enriched": { "function": "Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation", "gene_name": "AGL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35573" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "medium", "disease": "Glycogen Storage Disease Type VI", "glycan_involvement": "Glycosylation affects PYGL activity.", "mechanism": "PYGL mutations impair glycogen phosphorylase, causing mild hepatomegaly and elevated transaminases.", "protein": "PYGL", "protein_enriched": { "function": "Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular", "gene_name": "PYGL", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G47702MW", "G49108TO" ], "uniprot_id": "P06737" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "medium", "disease": "Glycogen Storage Disease Type IXa", "glycan_involvement": "Glycosylation required for PHKA2 complex assembly.", "mechanism": "PHKA2 mutations reduce phosphorylase kinase activity, leading to impaired glycogen breakdown.", "protein": "PHKA2", "protein_enriched": { "function": "Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen", "gene_name": "CDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16878" }, "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "medium", "disease": "Citrin deficiency", "glycan_involvement": "Glycosylation may affect SLC25A13 mitochondrial import.", "mechanism": "SLC25A13 mutations disrupt aspartate-glutamate transport, causing metabolic liver dysfunction.", "protein": "SLC25A13", "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "medium", "disease": "Novel bile acid biosynthesis defect", "glycan_involvement": "Glycosylation may regulate ABCD3 membrane targeting.", "mechanism": "ABCD3 mutations impair peroxisomal bile acid intermediate transport, leading to cholestasis and fibrosis.", "protein": "ABCD3", "relationship_type": "causal", "source_pmcid": "PMC12576671" }, { "confidence": "high", "disease": "Breast Adenocarcinoma", "glycan_involvement": "Mucin-type O-glycosylation critical for PDPN function and detection.", "mechanism": "PDPN expression in lymphatic microvessels marks neo-lymphangiogenesis and correlates with aggressive tumor phenotype and advanced stage.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "high", "disease": "Invasive Ductal Breast Carcinoma (inDBC)", "glycan_involvement": "O-glycosylation enables PDPN's role in lymphatic endothelium.", "mechanism": "High PDPN-dependent lymphatic microvessel density (mLMVD) is associated with advanced stage and poor prognosis.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "high", "disease": "Invasive Lobular Breast Carcinoma (inLBC)", "glycan_involvement": "O-glycosylation required for PDPN membrane localization.", "mechanism": "PDPN expression and mLMVD correlate with tumor aggressiveness, independent of histotype.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "high", "disease": "Lymph Node Metastasis", "glycan_involvement": "Glycosylation supports PDPN's adhesive and migratory functions.", "mechanism": "PDPN overexpression in neo-lymphatic structures facilitates lymphatic invasion and metastatic spread.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "causal", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Triple-negative Breast Cancer", "glycan_involvement": "O-glycosylation modulates PDPN's interaction with lymphatic endothelium.", "mechanism": "PDPN overexpression in subareolar Sappey's plexus correlates with lymphogenous metastasis to axillary lymph nodes.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Inflammatory Breast Cancer", "glycan_involvement": "Glycosylation enhances PDPN's pro-lymphangiogenic activity.", "mechanism": "Combined overexpression of PDPN and VEGF C-D is associated with increased tumor emboli.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Breast Adenocarcinoma", "glycan_involvement": "Ganglioside glycan structure mediates cell signaling and adhesion.", "mechanism": "GD2 involved in cancer stem cell activation, EMT, lymphovascular invasion, and interacts with PDPN.", "protein": "Disialoganglioside GD2", "relationship_type": "causal", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Breast Adenocarcinoma", "glycan_involvement": "Targeting glycosylation may affect PDPN function.", "mechanism": "PDPN inhibition proposed as a strategy to block lymphangiogenesis and metastasis.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Breast Adenocarcinoma (poorly differentiated)", "glycan_involvement": "Glycosylation status may modulate PDPN's interaction with other EMT markers.", "mechanism": "Combined overexpression of PDPN, PDGFR-\u03b2, and MMPs is frequent in EMT-high, poorly differentiated cases.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "medium", "disease": "Breast Adenocarcinoma (aggressive phenotype)", "glycan_involvement": "Glycosylation may influence PDPN's role in EMT.", "mechanism": "Combined overexpression of PDPN and Twist correlates with aggressive phenotype and EMT.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12577617" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Sialylated oligosaccharide structure mediates selectin binding and immune modulation.", "mechanism": "Promotes cancer progression and metastasis via interaction with endothelial selectins, facilitating tumor cell adhesion and dissemination; may contribute to immunosuppression.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12577629" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Mucin-type O-glycosylation contributes to antigenicity and tumor association.", "mechanism": "High expression correlates with poor prognosis and unresectable tumors.", "protein": "CA724 (TAG-72)", "relationship_type": "biomarker", "source_pmcid": "PMC12577629" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation affects secretion and extracellular matrix interactions.", "mechanism": "High expression associated with metastasis and worse prognosis; involved in cell adhesion via integrins and CD36.", "protein": "THBS2", "relationship_type": "biomarker", "source_pmcid": "PMC12577629" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycan epitope recognized by diagnostic antibodies.", "mechanism": "Overexpression associated with tumors in the body/tail of the pancreas, which have poorer prognosis.", "protein": "CA242", "relationship_type": "biomarker", "source_pmcid": "PMC12577629" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycan epitope mediates antigenicity.", "mechanism": "Significant predictor of survival in univariable analysis.", "protein": "CA50", "relationship_type": "biomarker", "source_pmcid": "PMC12577629" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may modulate protein stability and function.", "mechanism": "Contributes to oxaliplatin resistance.", "protein": "THBS2", "relationship_type": "causal", "source_pmcid": "PMC12577629" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Extensive O-glycosylation characteristic of mucins.", "mechanism": "Assessed as a tissue biomarker; not significant in this study.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker (investigational)", "source_pmcid": "PMC12577629" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation may affect secretion.", "mechanism": "Assessed as a tissue biomarker; not significant in this study.", "protein": "TFF1", "relationship_type": "biomarker (investigational)", "source_pmcid": "PMC12577629" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation may affect secretion.", "mechanism": "Assessed as a tissue biomarker; not significant in this study.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker (investigational)", "source_pmcid": "PMC12577629" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation may affect secretion.", "mechanism": "Assessed as a tissue biomarker; not significant in this study.", "protein": "MMP7", "relationship_type": "biomarker (investigational)", "source_pmcid": "PMC12577629" }, { "confidence": "high", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "Complex is a carbohydrate-containing glycoprotein; glycosylation is essential for function.", "mechanism": "Deficiency or absence of the complex impairs platelet adhesion to vWF, causing bleeding.", "protein": "Glycoprotein Ib\u2013IX\u2013V complex", "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "high", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "GPIb\u03b1 is glycosylated; glycosylation affects receptor function and stability.", "mechanism": "Mutation or reduced expression leads to defective platelet-vWF interaction and bleeding.", "protein": "GPIb\u03b1 (CD42a)", "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "high", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation required for proper folding and surface expression.", "mechanism": "Genetic mutations reduce or eliminate GPIb\u03b2, impairing complex assembly and platelet function.", "protein": "GPIb\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "high", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation influences stability and surface localization.", "mechanism": "Mutations in GPIX gene disrupt complex formation, leading to bleeding phenotype.", "protein": "GPIX", "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "medium", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Deficiency contributes to impaired platelet adhesion and aggregation.", "protein": "GPV", "protein_enriched": { "function": "Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and", "gene_name": "Rabggtb", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q08603" }, "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "high", "disease": "von Willebrand disease (vWD)", "glycan_involvement": "vWF is heavily glycosylated; glycosylation affects multimerization and function.", "mechanism": "Deficiency or dysfunction of vWF leads to impaired platelet adhesion and bleeding.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12577837" }, { "confidence": "medium", "disease": "von Willebrand disease (vWD)", "glycan_involvement": "Glycosylation status may affect diagnostic assays.", "mechanism": "Normal expression differentiates vWD from BSS in diagnostic testing.", "protein": "Glycoprotein Ib\u2013IX\u2013V complex", "relationship_type": "biomarker", "source_pmcid": "PMC12577837" }, { "confidence": "medium", "disease": "Bernard\u2013Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation required for integrin function.", "mechanism": "Normal expression in BSS helps distinguish from other platelet disorders.", "protein": "GPIIb/IIIa (CD41/CD61)", "relationship_type": "biomarker", "source_pmcid": "PMC12577837" }, { "confidence": "medium", "disease": "Immune thrombocytopenic purpura (ITP)", "glycan_involvement": "Glycosylation not directly implicated in ITP.", "mechanism": "Normal expression in ITP helps differentiate from BSS.", "protein": "Glycoprotein Ib\u2013IX\u2013V complex", "relationship_type": "biomarker", "source_pmcid": "PMC12577837" }, { "confidence": "low", "disease": "Sickle cell disease", "glycan_involvement": "Glycosylation status not directly implicated.", "mechanism": "Platelet defects in sickle cell disease may mimic BSS but are not caused by glycoprotein deficiency.", "protein": "Glycoprotein Ib\u2013IX\u2013V complex", "relationship_type": "biomarker", "source_pmcid": "PMC12577837" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "GP is heavily glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "GP mediates viral entry via NPC1, triggers endothelial cytotoxicity and immune dysregulation.", "protein": "Ebola virus glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "high", "disease": "Hemorrhage", "glycan_involvement": "Glycosylation of GP enhances cytotoxicity and immune escape.", "mechanism": "GP induces endothelial cell detachment, apoptosis, and barrier dysfunction.", "protein": "Ebola virus glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "N-glycosylation required for antiviral activity.", "mechanism": "Lactoferrin inhibits viral entry and replication; released by neutrophils.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "Glycosylation modulates peptide stability and activity.", "mechanism": "Defensins disrupt viral envelope and inhibit replication.", "protein": "Defensins", "relationship_type": "protective", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "O-glycosylation affects peptide function.", "mechanism": "LL-37 has broad-spectrum antiviral activity, modulates immune response.", "protein": "Cathelicidin (LL-37)", "protein_enriched": { "function": "Antimicrobial protein that is an integral component of the innate immune system (PubMed:14978112, PubMed:16637646, PubMed:18818205, PubMed:22879591, PubMed:9736536). Binds to bacterial lipopolysacchar", "gene_name": "CAMP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P49913" }, "relationship_type": "protective", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Multi-organ failure", "glycan_involvement": "Glycosylation influences enzyme stability and secretion.", "mechanism": "Excessive release during neutrophil degranulation causes tissue damage.", "protein": "Myeloperoxidase", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Histone glycosylation modulates NET formation.", "mechanism": "NETs promote thrombosis and endothelial injury.", "protein": "Histones (NET component)", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "Glycosylation regulates receptor binding and function.", "mechanism": "Mediates antibody-dependent cellular cytotoxicity (ADCC) against opsonized EBOV.", "protein": "Fc receptor (CD16)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12577865" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "NPC1 glycosylation affects GP binding and viral fusion.", "mechanism": "NPC1 is the host receptor for EBOV GP, essential for viral entry.", "protein": "Niemann-Pick C1 (NPC1)", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "TLR4 glycosylation modulates ligand recognition and signaling.", "mechanism": "TLR4 recognizes EBOV GP, triggers excessive cytokine release.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12577865" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Non-enzymatic glycation enhances GPIb function and adhesion.", "mechanism": "GPIb mediates platelet adhesion to dysfunctional endothelium, promoting atherogenesis.", "protein": "Glycoprotein Ib (GPIb)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Non-enzymatic glycation increases aggregation propensity.", "mechanism": "Glycated and overexpressed GPIIb/IIIa increases fibrinogen binding and platelet aggregation.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycoprotein nature facilitates cell-cell interactions.", "mechanism": "Elevated P-selectin promotes leukocyte recruitment and endothelial activation.", "protein": "P-selectin (CD62P)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycoprotein structure supports immune signaling.", "mechanism": "High CD40L on platelets enhances inflammation and plaque instability.", "protein": "CD40 ligand (CD40L)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation critical for vWF-platelet binding.", "mechanism": "vWF interacts with GPIb to mediate platelet adhesion and thrombus formation.", "protein": "Von Willebrand Factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycoprotein release from activated platelets.", "mechanism": "PF4 released from platelets promotes microvascular occlusion and inflammation.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Acute Coronary Syndrome (ACS)", "glycan_involvement": "Glycation may alter receptor function.", "mechanism": "Enhanced thromboxane signaling increases platelet aggregation and thrombus stability.", "protein": "Thromboxane A2 receptor", "protein_enriched": { "function": "Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger", "gene_name": "TBXA2R", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21731" }, "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycoprotein secretion from platelets.", "mechanism": "Platelet-derived TGF-\u03b2 promotes glomerular fibrosis and endothelial injury.", "protein": "Transforming Growth Factor-beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycoprotein release from \u03b1-granules.", "mechanism": "PDGF from platelets stimulates smooth muscle proliferation in plaques.", "protein": "Platelet-derived Growth Factor (PDGF)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Glycoprotein released during platelet activation.", "mechanism": "Platelet-derived VEGF promotes neovascularization and vascular leakage.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12579010" }, { "confidence": "high", "disease": "Vascular leakage/edema", "glycan_involvement": "Glycosylation stabilizes VE-cadherin at junctions, affecting barrier integrity.", "mechanism": "Phosphorylation of VE-cadherin at Y685 by pro-inflammatory agents increases vascular leakage; dephosphorylation at Y731 enables leukocyte TEM without leakage.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Vascular leakage/edema", "glycan_involvement": "N-glycosylation modulates ICAM-1 clustering and leukocyte binding.", "mechanism": "ICAM-1 clustering triggers actin cytoskeletal rearrangements and formation of contractile F-actin rings, restricting leakage during leukocyte TEM.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12579809" }, { "confidence": "medium", "disease": "Vascular leakage/edema", "glycan_involvement": "N-glycosylation required for ligand binding and clustering.", "mechanism": "VCAM-1 clustering promotes leukocyte adhesion and transmigration; excessive signaling can disrupt barrier.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Allergic inflammation", "glycan_involvement": "Binds sialyl Lewis X glycans on leukocytes.", "mechanism": "E-selectin mediates leukocyte rolling and recruitment to inflamed endothelium.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Ischemia\u2013reperfusion injury", "glycan_involvement": "Binds sialylated, fucosylated glycans on PSGL-1.", "mechanism": "P-selectin mediates leukocyte rolling; blockade reduces vascular leakage in injury models.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12579809" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "L-selectin on leukocytes mediates recruitment to inflamed endothelium, contributing to chronic inflammation.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "causal", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "O-glycosylation and sialyl Lewis X essential for selectin binding.", "mechanism": "PSGL-1 mediates leukocyte rolling via P-selectin; blockade reduces excessive leukocyte recruitment and leakage.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12579809" }, { "confidence": "medium", "disease": "Vascular leakage/edema", "glycan_involvement": "N-glycosylation supports homophilic interactions.", "mechanism": "PECAM-1 mediates diapedesis at cell junctions, facilitating leukocyte passage without barrier disruption.", "protein": "PECAM-1", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for eff", "gene_name": "Pecam1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G25079LO", "G24748EV", "G15664MX", "G72747WU", "G31986NC", "G80920RR", "G49108TO" ], "uniprot_id": "Q08481" }, "relationship_type": "protective", "source_pmcid": "PMC12579809" }, { "confidence": "medium", "disease": "Vascular leakage/edema", "glycan_involvement": "Glycosylation stabilizes GPVI-collagen interaction.", "mechanism": "GPVI on platelets binds exposed collagen at sites of endothelial disruption, sealing the barrier and preventing leakage.", "protein": "GPVI", "relationship_type": "protective", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Vascular leakage/edema", "glycan_involvement": "N-glycosylation required for receptor function and ligand binding.", "mechanism": "Tie-2 activation by Ang1 (from platelets) strengthens endothelial junctions and prevents leakage during inflammation.", "protein": "Tie-2", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12579809" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin by glucose.", "mechanism": "HbA1c reflects long-term glycemic control; higher levels associated with CKD progression in T2DM.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Non-enzymatic glycation of serum proteins (mainly albumin).", "mechanism": "Fructosamine reflects short-term glycemic control; levels rise as renal function declines due to reduced clearance.", "protein": "Fructosamine", "relationship_type": "biomarker", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Non-enzymatic glycation of proteins and lipids; AGEs formation and accumulation.", "mechanism": "AGEs accumulate in CKD due to impaired clearance, promoting inflammation, oxidative stress, and fibrosis.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "AGEs interact with RAGE, activating pro-inflammatory and pro-fibrotic pathways.", "mechanism": "AGEs induce podocyte injury and fibrosis via RAGE signaling, accelerating nephropathy.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12580507" }, { "confidence": "medium", "disease": "Proteinuria", "glycan_involvement": "Altered glycosylation affects podocyte protein structure/function.", "mechanism": "Abnormal glycosylation of podocyte proteins disrupts glomerular filtration barrier, increasing permeability.", "protein": "Podocyte proteins", "relationship_type": "causal", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "RAGE binds AGEs, initiating downstream signaling.", "mechanism": "AGE-RAGE interaction triggers oxidative stress and inflammation, worsening CKD.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "causal", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Reflects average blood glucose via glycation of hemoglobin.", "mechanism": "HbA1c is the gold standard for long-term glycemic monitoring in T2DM.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Reflects glycation of serum proteins over 2-3 weeks.", "mechanism": "Fructosamine is useful for short-term glycemic monitoring, especially when HbA1c is unreliable.", "protein": "Fructosamine", "relationship_type": "biomarker", "source_pmcid": "PMC12580507" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "AGEs accumulate and interact with vascular proteins.", "mechanism": "AGEs promote vascular inflammation and endothelial dysfunction, increasing CVD risk in T2DM and CKD.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Chronic hyperglycemia leads to increased hemoglobin glycation.", "mechanism": "Higher HbA1c levels are associated with increased risk and progression of diabetic nephropathy.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12580507" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Defective N-glycosylation of proteins due to impaired mannose metabolism.", "mechanism": "Mutations in PMM2 impair N-glycan assembly, leading to multisystem disease.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12580737" }, { "confidence": "high", "disease": "Cerebellar ataxia", "glycan_involvement": "Impaired N-glycosylation in neural tissues.", "mechanism": "PMM2 deficiency leads to abnormal glycosylation affecting cerebellar development and function.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12580737" }, { "confidence": "medium", "disease": "Retinitis pigmentosa", "glycan_involvement": "Abnormal N-glycosylation of retinal glycoproteins.", "mechanism": "Defective glycosylation impacts retinal proteins, leading to degeneration.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12580737" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Defective N-glycosylation of neural glycoproteins.", "mechanism": "Impaired glycosylation affects neuronal function and axonal integrity.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12580737" }, { "confidence": "medium", "disease": "Intellectual deficiency", "glycan_involvement": "Impaired N-glycosylation in brain development.", "mechanism": "Abnormal glycosylation disrupts neurodevelopmental processes.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12580737" }, { "confidence": "high", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Abnormal N-glycosylation pattern of transferrin.", "mechanism": "Altered glycoforms of transferrin detected by isoelectric focusing indicate CDG.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12580737" }, { "confidence": "medium", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Additional defects in N-glycan assembly.", "mechanism": "ALG6 variants worsen PMM2-CDG symptoms by further impairing glycosylation.", "protein": "ALG6", "protein_enriched": { "function": "Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)", "gene_name": "ALG6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9Y672" }, "relationship_type": "modifier", "source_pmcid": "PMC12580737" }, { "confidence": "low", "disease": "PMM2-Congenital Disorder of Glycosylation (PMM2-CDG)", "glycan_involvement": "Alternative glycosylation pathway compensation.", "mechanism": "PGM1 variants may compensate for PMM2 deficiency, modulating disease severity.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "protective", "source_pmcid": "PMC12580737" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Multivalent N-glycosylation enhances lectin binding, facilitating detection.", "mechanism": "Altered N-glycan patterns on HSA can serve as biomarkers for cancer detection.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycan clustering modulates lectin recognition.", "mechanism": "Changes in glycosylation of serum proteins are associated with inflammatory states.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "Multivalent N-glycosylation increases detection sensitivity.", "mechanism": "Glycan patterns on serum proteins reflect infection status and immune response.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Recognition of specific O-glycan structures on tumor cells.", "mechanism": "PNA binds to Gal-\u03b2(1,3)-GalNAc residues, which are upregulated in certain cancers.", "protein": "Peanut Agglutinin (PNA)", "protein_enriched": { "function": "D-galactose specific lectin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02872" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "medium", "disease": "Autoimmune Disease", "glycan_involvement": "Changes in sialylation affect immune modulation.", "mechanism": "SNA binding to \u03b1(2,6)-sialylated glycans is altered in autoimmune conditions.", "protein": "Sambucus nigra Agglutinin (SNA)", "protein_enriched": { "function": "Probable chromatin remodeling factor", "gene_name": "CLSY3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F4I8S3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "high", "disease": "Host\u2013Pathogen Recognition", "glycan_involvement": "Sialylation mediates host\u2013pathogen interactions.", "mechanism": "SNA recognizes sialic acid residues involved in pathogen binding and immune evasion.", "protein": "Sambucus nigra Agglutinin (SNA)", "protein_enriched": { "function": "Probable chromatin remodeling factor", "gene_name": "CLSY3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F4I8S3" }, "relationship_type": "causal", "source_pmcid": "PMC12581113" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Altered O-glycosylation on immune cells.", "mechanism": "PNA binding reflects changes in glycan expression during inflammation.", "protein": "Peanut Agglutinin (PNA)", "protein_enriched": { "function": "D-galactose specific lectin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02872" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "low", "disease": "Autoimmune Disease", "glycan_involvement": "N-glycan clustering affects immune recognition.", "mechanism": "Aberrant glycosylation of HSA is associated with autoimmune pathogenesis.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "medium", "disease": "Host\u2013Pathogen Recognition", "glycan_involvement": "Galactosylation patterns facilitate pathogen binding.", "mechanism": "PNA binding to galactosylated glycans mediates cell\u2013cell and pathogen recognition.", "protein": "Peanut Agglutinin (PNA)", "protein_enriched": { "function": "D-galactose specific lectin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02872" }, "relationship_type": "causal", "source_pmcid": "PMC12581113" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Increased \u03b1(2,6)-sialylation on glycoproteins.", "mechanism": "Altered sialylation detected by SNA is a hallmark of cancer progression.", "protein": "Sambucus nigra Agglutinin (SNA)", "protein_enriched": { "function": "Probable chromatin remodeling factor", "gene_name": "CLSY3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "F4I8S3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581113" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "SPARC is a glycoprotein; glycosylation is required for its extracellular matrix interactions and cell signaling.", "mechanism": "SPARC promotes pancreatic \u03b2-cell regeneration and enhances insulin secretion by increasing intracellular ATP and Ca2+ influx.", "protein": "SPARC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12581257" }, { "confidence": "high", "disease": "Canine Diabetes Mellitus", "glycan_involvement": "Glycosylation of SPARC is essential for its function in cell adhesion and migration.", "mechanism": "SPARC-modified MSCs reduce hyperglycemia, restore islet area, and improve glucose tolerance in diabetic canines.", "protein": "SPARC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12581257" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates SPARC's stability and interaction with \u03b2-cells.", "mechanism": "SPARC overexpression in \u03b2-cells cultured under high glucose increases insulin secretion and \u03b2-cell survival.", "protein": "SPARC", "relationship_type": "protective", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects SPARC's extracellular matrix binding and signaling.", "mechanism": "SPARC promotes collagen formation and inhibits adipogenesis via \u03b2-catenin signaling.", "protein": "SPARC", "relationship_type": "causal", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Wound Healing", "glycan_involvement": "Glycosylation is necessary for SPARC's role in extracellular matrix remodeling.", "mechanism": "SPARC is overexpressed during tissue repair, facilitating cell migration and regeneration.", "protein": "SPARC", "relationship_type": "protective", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation influences SPARC's immunomodulatory functions.", "mechanism": "SPARC regulates inflammatory responses and cell migration.", "protein": "SPARC", "relationship_type": "modulator", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects SPARC's interaction with tumor microenvironment.", "mechanism": "SPARC is implicated in tumor progression and cell migration.", "protein": "SPARC", "relationship_type": "modulator", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation status may influence SPARC's biomarker potential.", "mechanism": "SPARC expression correlates with \u03b2-cell survival and insulin secretion in diabetic models.", "protein": "SPARC", "relationship_type": "biomarker", "source_pmcid": "PMC12581257" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation is required for SPARC's extracellular matrix and signaling functions.", "mechanism": "SPARC-modified MSCs enrich calcium binding and cell migration pathways, aiding \u03b2-cell recovery.", "protein": "SPARC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12581257" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation may modulate SPARC's regulatory effects on RGS4.", "mechanism": "SPARC downregulates RGS4 in pancreatic \u03b2-cells, increasing insulin secretion.", "protein": "SPARC", "relationship_type": "protective", "source_pmcid": "PMC12581257" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "N-glycosylation modulates ICAM-1 stability and cell adhesion.", "mechanism": "Elevated ICAM-1 reflects endothelial and leukocyte activation, correlating with PTS severity.", "protein": "Intercellular adhesion molecule 1 (ICAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation required for ligand binding and selectin function.", "mechanism": "Increased soluble E-selectin in severe PTS indicates endothelial activation.", "protein": "E-selectin (CD62E)", "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation essential for selectin-mediated cell adhesion.", "mechanism": "Elevated P-selectin in severe PTS reflects platelet and endothelial activation.", "protein": "P-selectin (CD62P)", "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation affects chemokine presentation and receptor interaction.", "mechanism": "Increased fractalkine correlates with PTS severity, mediates leukocyte recruitment.", "protein": "Fractalkine (CX3CL1)", "protein_enriched": { "function": "Chemokine that acts as a ligand for both CX3CR1 and integrins ITGAV:ITGB3 and ITGA4:ITGB1 (PubMed:12055230, PubMed:21829356, PubMed:23125415, PubMed:9782118, PubMed:9931005). The CX3CR1-CX3CL1 signali", "gene_name": "CX3CL1", "glycan_count": 12, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G53434XO", "G57321FI", "G29931IJ", "G43417UB", "G81006GJ", "G29068FM", "G41071NU", "G43223CG", "G45395BF", "G78790NZ", "G80075MS", "G87661QW" ], "uniprot_id": "P78423" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "medium", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "N-glycosylation influences CRP solubility and immune recognition.", "mechanism": "CRP is elevated in early PTS, reflecting systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "medium", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation affects HRG plasma half-life and interaction with heparin.", "mechanism": "HRG is increased in PTS, modulates fibrinolysis and vascular repair.", "protein": "Histidine-rich glycoprotein (HRG)", "protein_enriched": { "function": "Plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. Binds heparin and heparin/glycosaminoglycans in a zinc-", "gene_name": "HRG", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G04854VP", "G05933EN", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10846ZT", "G11911BT", "G12341GU", "G14972EH", "G15664MX", "G17208MA", "G18647XP", "G22572EH", "G23294PN", "G25418HZ", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28681TP", "G29299MO", "G31986NC", "G36379GD", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G39446WN", "G40206WX", "G40574BA", "G40834TG", "G41247ZX", "G41840AI", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45504EY", "G45526EA", "G46524LG", "G46691LC", "G46902YN", "G48414YA", "G49018RC", "G49906RN", "G50045TK", "G50856PC", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G61256FT", "G63980BQ", "G65000LJ", "G65414LI", "G70232NH", "G70619PT", "G72291OX", "G72747WU", "G75983OB", "G76295SF", "G77547TA", "G80920RR", "G81637OR", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85269DF", "G85554PZ", "G89098OM", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G95977AE", "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G31665QC", "G33791AF", "G47737VJ", "G55412XP", "G60923RB", "G71560PC", "G85144OK", "G88374WZ", "G89205CJ", "G92135MA", "G27947YN", "G22310AV", "G24084IV", "G47518TP", "G49108TO" ], "uniprot_id": "P04196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation required for multimerization and bioactivity.", "mechanism": "Higher adiponectin inversely correlates with PTS severity; anti-inflammatory and endothelial protective.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation influences leptin secretion and receptor binding.", "mechanism": "Elevated leptin correlates with PTS severity; promotes prothrombotic and inflammatory states.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation modulates MMP secretion and activity.", "mechanism": "MMP-1 increased in PTS; mediates vein wall remodeling and fibrosis.", "protein": "Matrix metalloproteinase-1 (MMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "Post-thrombotic syndrome (PTS)", "glycan_involvement": "Glycosylation affects MMP-8 stability and substrate specificity.", "mechanism": "MMP-8 increased in PTS; involved in extracellular matrix degradation.", "protein": "Matrix metalloproteinase-8 (MMP-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12581707" }, { "confidence": "high", "disease": "muscular dystrophy", "glycan_involvement": "Proper glycosylation of \u03b1-dystroglycan is required for laminin binding and muscle membrane stability.", "mechanism": "Loss or disruption of \u03b1-dystroglycan impairs muscle fiber adhesion and integrity, contributing to muscular dystrophy.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12581944" }, { "confidence": "high", "disease": "muscular dystrophy", "glycan_involvement": "Laminin binding depends on glycosylation of \u03b1-dystroglycan.", "mechanism": "Defective interaction between laminin and \u03b1-dystroglycan leads to muscle membrane instability.", "protein": "laminin", "relationship_type": "causal", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "muscle fiber dedifferentiation", "glycan_involvement": "Glycosylation status affects \u03b1-dystroglycan detection and function.", "mechanism": "Loss of \u03b1-dystroglycan staining indicates dedifferentiation and loss of membrane integrity in cultured muscle fibers.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "skeletal muscle atrophy", "glycan_involvement": "Fibrinogen is a glycoprotein; its matrix properties may be influenced by glycosylation.", "mechanism": "Embedding muscle fibers in fibrin hydrogel preserves viability and contractile function, reducing atrophy.", "protein": "fibrinogen", "relationship_type": "protective", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "muscle fiber dedifferentiation", "glycan_involvement": "Laminin is a glycoprotein; its interaction with \u03b1-dystroglycan is glycan-dependent.", "mechanism": "Laminin coating promotes muscle fiber adhesion and reduces dedifferentiation in culture.", "protein": "laminin", "relationship_type": "protective", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "skeletal muscle atrophy", "glycan_involvement": "Glycosylation is essential for \u03b1-dystroglycan function.", "mechanism": "Recovery of \u03b1-dystroglycan on muscle fiber membranes correlates with improved viability and reduced atrophy.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "skeletal muscle atrophy", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Disorganization of the microtubule network impairs contractile function and contributes to muscle fiber atrophy.", "protein": "microtubule-associated proteins", "relationship_type": "causal", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "muscular dystrophy", "glycan_involvement": "Targeting glycosylation pathways can restore \u03b1-dystroglycan function.", "mechanism": "Restoration of \u03b1-dystroglycan glycosylation may improve muscle fiber integrity and function.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12581944" }, { "confidence": "medium", "disease": "muscular dystrophy", "glycan_involvement": "Glycosylation of \u03b1-dystroglycan is required for laminin binding.", "mechanism": "Enhancing laminin-\u03b1-dystroglycan interaction may stabilize muscle membranes.", "protein": "laminin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12581944" }, { "confidence": "low", "disease": "muscle fiber dedifferentiation", "glycan_involvement": "Fibrinogen glycosylation may affect matrix properties.", "mechanism": "Fibrin hydrogel environment reduces dedifferentiation of muscle fibers in culture.", "protein": "fibrinogen", "relationship_type": "protective", "source_pmcid": "PMC12581944" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation, ALG2 type)", "glycan_involvement": "Defective N-glycosylation; accumulation of immature/high-mannose and hyposialylated N-glycans.", "mechanism": "Pathogenic variants in ALG2 disrupt N-glycan biosynthesis, leading to multisystem disease including neurological and ocular symptoms.", "protein": "ALG2 (\u03b1-1,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "high", "disease": "Ophthalmic Manifestations of CDG", "glycan_involvement": "Incomplete N-glycan chains on cell-surface glycoproteins in photoreceptors.", "mechanism": "ALG2 deficiency impairs glycosylation in retinal photoreceptors, causing degeneration and cell death.", "protein": "ALG2 (\u03b1-1,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "Congenital Myasthenic Syndrome (CMS)", "glycan_involvement": "Defective N-glycosylation of synaptic proteins.", "mechanism": "ALG2 mutations affect N-glycosylation at neuromuscular junction, impairing synaptic function.", "protein": "ALG2 (\u03b1-1,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "high", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation, ALG2 type)", "glycan_involvement": "Altered N-glycosylation pattern detectable by mass spectrometry.", "mechanism": "Serum transferrin glycoforms are altered (hyposialylated, increased fucosylation) in ALG2-CDG patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "ALG12-CDG", "glycan_involvement": "Defective N-glycosylation; similar glycan abnormalities as ALG2-CDG.", "mechanism": "ALG12 deficiency disrupts N-glycan biosynthesis, leading to accumulation of high-mannose glycoproteins.", "protein": "ALG12 (\u03b1-1,6-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "low", "disease": "Ophthalmic Manifestations of CDG", "glycan_involvement": "Altered N-glycosylation affects IRBP function in photoreceptors.", "mechanism": "Glycosylation defects in IRBP may contribute to retinal dysfunction in CDG.", "protein": "IRBP (Interphotoreceptor Retinoid-Binding Protein)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "Retinitis Pigmentosa", "glycan_involvement": "N-glycosylation required for opsin stability and function.", "mechanism": "Defective glycosylation of cone opsins impairs photoreceptor survival, contributing to retinal degeneration.", "protein": "Cone Opsins", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "Retinitis Pigmentosa", "glycan_involvement": "Defective N-glycosylation in retinal cells.", "mechanism": "ALG2 mutations lead to photoreceptor degeneration via impaired glycosylation.", "protein": "ALG2 (\u03b1-1,3-mannosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Altered N-glycosylation of retinal proteins.", "mechanism": "PMM2 mutations cause N-glycosylation defects, leading to photoreceptor dysfunction.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC12582550" }, { "confidence": "medium", "disease": "ALG2-CDG (Congenital Disorder of Glycosylation, ALG2 type)", "glycan_involvement": "Targeting N-glycosylation pathway for therapy.", "mechanism": "Restoring ALG2 function or correcting glycosylation may ameliorate disease symptoms.", "protein": "ALG2 (\u03b1-1,3-mannosyltransferase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12582550" }, { "confidence": "high", "disease": "Colon adenocarcinoma (COAD)", "glycan_involvement": "Promotes \u03b2-1,6 branching of N-glycans on glycoproteins.", "mechanism": "MGAT5 is highly expressed in COAD tissues and cell lines; correlates with poor disease-free survival.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "biomarker", "source_pmcid": "PMC12582788" }, { "confidence": "high", "disease": "Colon adenocarcinoma (COAD)", "glycan_involvement": "Alters N-glycan branching, affecting immune synapse formation and immune cell recruitment.", "mechanism": "MGAT5 modulates immune cell infiltration and may be targeted for immunotherapy.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12582788" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "\u03b2-1,6-branched N-glycans increase cell motility and invasion.", "mechanism": "MGAT5 enhances metastasis by modifying glycosylation of TIMP-1, ZO-1, and cell adhesion molecules.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Immune escape in cancer", "glycan_involvement": "N-glycan branching reduces T cell activation and cytotoxicity.", "mechanism": "MGAT5 protects tumor cells from T cell killing by interfering with immune synapse formation.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Produces bisecting GlcNAc N-glycans, which suppress metastasis.", "mechanism": "MGAT3 is associated with cancer suppression via N-glycan modification.", "protein": "MGAT3", "relationship_type": "protective", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Core fucosylation of N-glycans affects tumor progression.", "mechanism": "FUT8 expression correlates with prognosis in stage II/III colorectal cancer.", "protein": "FUT8", "relationship_type": "biomarker", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "Altered N-glycosylation disrupts TIMP-1 function.", "mechanism": "MGAT5-mediated glycosylation of TIMP-1 impairs its gelatinase inhibition, increasing metastatic potential.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N-glycan modification leads to protein instability.", "mechanism": "MGAT5 facilitates ZO-1 ubiquitination and degradation, promoting metastasis.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation increases MT1-MMP activity.", "mechanism": "MGAT5 stimulates MT1-MMP expression, enhancing proteolytic activity and invasion.", "protein": "MT1-MMP", "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "medium", "disease": "Colon adenocarcinoma (COAD)", "glycan_involvement": "N-glycan branching enhances receptor signaling.", "mechanism": "MGAT5 catalyzes \u03b21,6-branched glycosylation of FZD-7, activating Wnt signaling and tumor progression.", "protein": "FZD-7", "protein_enriched": { "function": "Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuc", "gene_name": "FZD3", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR", "G82390KS" ], "uniprot_id": "Q9NPG1" }, "relationship_type": "causal", "source_pmcid": "PMC12582788" }, { "confidence": "high", "disease": "Graves\u2019 disease (GD)", "glycan_involvement": "Increase in agalactosylated N-glycans (IGP55)", "mechanism": "Elevated agalactosylated IgG N-glycan structures (IGP55) increase GD risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Graves\u2019 disease (GD)", "glycan_involvement": "Specific N-glycan traits (IGP11, IGP51) inversely associated", "mechanism": "Higher levels of IGP11 and IGP51 N-glycan traits are associated with reduced GD risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune thyroiditis (AT)", "glycan_involvement": "Elevated IGP15, IGP59, IGP61 N-glycan traits", "mechanism": "Increased fucosylated, galactosylated, monosialylated, and digalactosylated IgG N-glycans (IGP15, IGP59, IGP61) raise AT risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune thyroiditis (AT)", "glycan_involvement": "Specific N-glycan traits inversely associated", "mechanism": "Higher levels of IGP6, IGP18, IGP31, IGP46 N-glycan traits are protective against AT", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune hyperthyroidism", "glycan_involvement": "Increase in IGP58, IGP59 N-glycan traits", "mechanism": "Elevated IGP58 and IGP59 N-glycan traits increase risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune hyperthyroidism", "glycan_involvement": "Specific N-glycan traits inversely associated", "mechanism": "Higher IGP11, IGP16, IGP21 N-glycan traits are protective", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune hypothyroidism (AH)", "glycan_involvement": "Increase in IGP17, IGP55 N-glycan traits", "mechanism": "Elevated IGP17 and IGP55 N-glycan traits increase AH risk", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12582811" }, { "confidence": "medium", "disease": "Graves\u2019 disease (GD)", "glycan_involvement": "IGP11 N-glycan trait modulates B cell phenotype", "mechanism": "IGP11 reduces GD risk via increased CD25 on CD24+ CD27+ B cells (immune cell mediation)", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (mediated)", "source_pmcid": "PMC12582811" }, { "confidence": "medium", "disease": "Autoimmune thyroiditis (AT)", "glycan_involvement": "IGP59 N-glycan trait modulates T cell phenotype", "mechanism": "IGP59 increases AT risk via HLA DR+ T cell % lymphocyte (immune cell mediation)", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (mediated)", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Autoimmune hyperthyroidism", "glycan_involvement": "IGP59 N-glycan trait increases \u03b2-NGF, promoting disease", "mechanism": "IGP59 increases risk via \u03b2-NGF (inflammatory cytokine mediation)", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (mediated)", "source_pmcid": "PMC12582811" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "P-gp is a membrane glycoprotein; glycosylation is essential for its stability and localization.", "mechanism": "P-gp overexpression causes efflux of chemotherapeutic drugs, leading to multidrug resistance; terpenoids downregulate P-gp to restore drug sensitivity.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "MRP1 is glycosylated; glycosylation affects trafficking and function.", "mechanism": "MRP1 mediates efflux of drugs and glutathione conjugates; terpenoids (e.g., parthenolide) downregulate MRP1 to reverse gemcitabine resistance.", "protein": "MRP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "BCRP is glycosylated; glycosylation required for membrane localization.", "mechanism": "BCRP expels chemotherapeutics; artesunate downregulates BCRP, increasing drug accumulation and efficacy.", "protein": "BCRP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Leukemia", "glycan_involvement": "Glycosylation critical for P-gp function.", "mechanism": "P-gp mediates drug efflux and resistance; triptolide, andrographolide, and nimbolide downregulate P-gp, restoring chemosensitivity.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "MRP1 glycosylation affects drug transport.", "mechanism": "MRP1 effluxes drugs; oridonin and tanshinone IIA inhibit MRP1, enhancing doxorubicin efficacy.", "protein": "MRP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Glycosylation required for P-gp activity.", "mechanism": "P-gp overexpression leads to MDR; cryptotanshinone, dihydrotanshinone, and limonin downregulate P-gp, reversing resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "BCRP glycosylation required for function.", "mechanism": "BCRP mediates drug efflux; ursolic acid downregulates BCRP, reversing MDR in ovarian cancer stem cells.", "protein": "BCRP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation stabilizes P-gp at membrane.", "mechanism": "P-gp effluxes drugs; wilforine, tenulin, isotenulin, and carnosic acid inhibit P-gp, restoring drug sensitivity.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation required for P-gp function.", "mechanism": "P-gp mediates MDR; cantharidin, alisol B 23-acetate, and parthenolide downregulate P-gp, reversing resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "Glycosylation required for P-gp activity.", "mechanism": "P-gp mediates drug efflux; euphomelliferine, betulinic acid, pomolic acid, uvaol, and \u03b2-amyrin downregulate P-gp, reversing MDR.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583261" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "Glycosylation of G protein is essential for receptor binding and infectivity.", "mechanism": "Glycoprotein G mediates viral entry by binding to LDLR on host cells, initiating infection.", "protein": "VSV Glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "LDLR is a glycoprotein; its glycosylation is required for proper folding and surface expression.", "mechanism": "LDLR acts as the cellular receptor for VSV, enabling viral entry via interaction with G protein.", "protein": "Low-Density Lipoprotein Receptor (LDLR)", "relationship_type": "causal", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "Loss of glycosylated G protein abrogates receptor-mediated entry.", "mechanism": "Deletion of G protein (\u0394G) in VSV prevents formation of infectious virions, enabling safer vaccine platforms.", "protein": "VSV Glycoprotein G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583722" }, { "confidence": "medium", "disease": "Nipah Virus Infection", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Envelope glycoprotein mediates host cell entry and is essential for Nipah virus infectivity.", "protein": "Nipah Virus Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12583722" }, { "confidence": "medium", "disease": "Vesicular Stomatitis", "glycan_involvement": "Glycosylation status can be used to confirm protein identity.", "mechanism": "Presence of G protein distinguishes infectious virions from non-infectious nucleocapsids.", "protein": "VSV Glycoprotein G", "relationship_type": "biomarker", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "Glycosylation affects LDLR surface expression and viral binding.", "mechanism": "Knockdown of LDLR reduces VSV infection, demonstrating its role in susceptibility.", "protein": "Low-Density Lipoprotein Receptor (LDLR)", "relationship_type": "protective", "source_pmcid": "PMC12583722" }, { "confidence": "medium", "disease": "Vesicular Stomatitis", "glycan_involvement": "Glycosylation not directly targeted by doxycycline but essential for G protein function.", "mechanism": "Antiviral screening (e.g., doxycycline) targets replication steps downstream of G protein-mediated entry.", "protein": "VSV Glycoprotein G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "Absence of glycosylated G protein disables receptor interaction.", "mechanism": "Use of G-deleted nucleocapsids (\u0394G) prevents spread of infectious virus, reducing biosafety risks.", "protein": "VSV Glycoprotein G", "relationship_type": "protective", "source_pmcid": "PMC12583722" }, { "confidence": "medium", "disease": "Nipah Virus Infection", "glycan_involvement": "Envelope glycoprotein glycosylation is required for infectivity; absence confers safety.", "mechanism": "Transport of Nipah virus NCs (lacking envelope glycoprotein) mitigates accidental infection risk.", "protein": "Nipah Virus Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "Vesicular Stomatitis", "glycan_involvement": "N-glycosylation is critical for G protein folding and function.", "mechanism": "G protein is required for virion assembly and host cell entry; its absence results in non-infectious particles.", "protein": "VSV Glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC12583722" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at Asn343 forms a glycan shield, blocking antibody access.", "mechanism": "Spike protein mediates viral entry and immune evasion via glycosylated Asn residues.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "Conserved N-glycosylated Asn residues facilitate protein-protein interactions.", "mechanism": "Spike protein interacts with hemoglobin and inflammatory mediators, triggering immune dysregulation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at Asn240 and Cys213 critical for receptor function and ligand binding.", "mechanism": "Elevated IL-17/IL-17R signaling predicts severe COVID-19 and poor outcomes.", "protein": "Interleukin-17 Receptor (IL-17R)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at Asn136 and Cys residues modulate receptor stability and signaling.", "mechanism": "IL-6/IL-6R axis is a key driver of inflammation and severity.", "protein": "Interleukin-6 Receptor (IL-6R)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "Autoimmune diseases (e.g., rheumatoid arthritis, psoriasis)", "glycan_involvement": "N-glycosylation at Asn240 and Cys residues essential for receptor-ligand interaction.", "mechanism": "IL-17R signaling implicated in autoimmune pathogenesis; targeted by monoclonal antibodies.", "protein": "Interleukin-17 Receptor (IL-17R)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates integrin-mediated cell adhesion and signaling.", "mechanism": "Altered integrin function contributes to platelet aggregation and thrombotic complications in COVID-19.", "protein": "CD41/CD61 (Integrin \u03b1IIb\u03b23)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12583749" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor-ligand interactions and immune modulation.", "mechanism": "CD47/SIRP\u03b1 axis regulates immune checkpoint and RBC clearance, contributing to hematological anomalies.", "protein": "CD47/SIRP\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "medium", "disease": "Post-COVID syndrome", "glycan_involvement": "Glycan shield on spike protein sustains immune evasion and chronic inflammation.", "mechanism": "Persistent spike protein-induced immune dysregulation linked to long-term complications.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation and disulfide bonds (Cys) are targeted by therapies to disrupt receptor function.", "mechanism": "Targeting IL-17R (e.g., with ASNase or monoclonal antibodies) can attenuate hyperinflammatory response.", "protein": "Interleukin-17 Receptor (IL-17R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation at Asn136 and Cys residues are therapeutic targets for receptor modulation.", "mechanism": "IL-6R inhibition (e.g., tocilizumab) reduces inflammation; glycan-targeting agents may enhance efficacy.", "protein": "Interleukin-6 Receptor (IL-6R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583749" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Autoantibodies against MOG are used to diagnose MOGAD, indicating its role as a disease biomarker.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12583754" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition.", "mechanism": "MOG is a target of autoimmune response in a subset of MS and is used to distinguish MOGAD from MS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12583754" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects collagen's structural integrity and cell interactions.", "mechanism": "Collagen hydrogels provide mechanical support and mimic ECM, promoting cardiac tissue regeneration post-MI.", "protein": "Collagen (Type I/II/IV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation modulates fibrin polymerization and cell binding.", "mechanism": "Fibrin hydrogels promote cell adhesion, distribution, and survival, aiding myocardial repair.", "protein": "Fibrinogen/Fibrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation critical for laminin's cell-binding domains.", "mechanism": "Laminin-rich Matrigel supports stem cell adhesion and growth, relevant for cardiac regeneration.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosaminoglycan chains mediate growth factor binding and cell signaling.", "mechanism": "Heparan sulfate in Matrigel enhances cell-matrix interactions and growth factor binding for tissue repair.", "protein": "Heparan sulfate proteoglycan", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "high", "disease": "Left ventricular remodeling", "glycan_involvement": "Glycosylation regulates MMP secretion and activity.", "mechanism": "MMPs degrade ECM glycoproteins, contributing to adverse remodeling post-MI.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "causal", "source_pmcid": "PMC12583852" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Integrin glycosylation modulates ligand binding and signaling.", "mechanism": "Hydrogel scaffolds with RGD motifs enhance integrin-mediated cell adhesion, improving cardiac repair.", "protein": "Integrins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Arrhythmia (electrical conduction defects)", "glycan_involvement": "Glycosylation affects trafficking and gap junction formation.", "mechanism": "Increased Connexin 43 expression in dECM hydrogels improves synchronous beating and electrical conduction.", "protein": "Connexin 43", "relationship_type": "biomarker", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may influence stability and function.", "mechanism": "Troponin T upregulation in dECM hydrogels marks cardiomyocyte differentiation and regeneration.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates fibronectin's cell-binding and matrix assembly.", "mechanism": "Fibronectin accumulation in ECM contributes to scar formation and fibrosis post-MI.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12583852" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Peptide glycosylation may enhance stability and bioactivity.", "mechanism": "QHREDGS-modified hydrogels promote cardiac function maintenance and reduce remodeling after MI.", "protein": "Angiopoietin-1 derived peptide (QHREDGS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12583852" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "CRP is an N-glycosylated protein; glycosylation affects its stability and immune recognition.", "mechanism": "CRP reflects systemic inflammation and is associated with increased mortality and hospitalization risk in HF.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Albumin is N-glycosylated; glycosylation modulates half-life and antioxidant properties.", "mechanism": "Low serum albumin indicates malnutrition and inflammation, correlating with higher mortality in HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Surface glycoproteins (e.g., CD antigens) are heavily glycosylated, affecting cell signaling and trafficking.", "mechanism": "Lymphocytopenia reflects impaired immune response and is linked to poor prognosis in HF.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "high", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "N-glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP predicts incident HFpEF and worse outcomes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "high", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "N-glycosylation influences albumin's stability and function.", "mechanism": "Hypoalbuminemia is associated with increased mortality in HFpEF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "CRP glycosylation affects its immune interactions.", "mechanism": "High CRP-to-lymphocyte ratio predicts cardiac mortality in dilated cardiomyopathy.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Acute decompensated heart failure", "glycan_involvement": "Albumin glycosylation modulates its antioxidant and transport functions.", "mechanism": "High CRP-to-albumin ratio predicts adverse outcomes in acute decompensated HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect CRP's pro-inflammatory activity.", "mechanism": "CRP-driven inflammation contributes to HF pathogenesis and progression.", "protein": "C-reactive protein", "relationship_type": "causal", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation enhances albumin's functional properties.", "mechanism": "Higher albumin levels reflect better nutritional and inflammatory status, conferring resilience in HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12584026" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation regulates lymphocyte activation and migration.", "mechanism": "Preserved lymphocyte counts indicate intact immune competence, reducing mortality risk.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12584026" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Cell surface glycosylation of T cells increases binding to Glut1 via glycopolymer engineering.", "mechanism": "Glut1-overexpressing cancer cells interact more strongly with glycopolymer-modified T cells, enhancing immune recognition.", "protein": "Glut1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584132" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glucose-based glycopolymer modification of tumor cells increases DC-SIGN-mediated DC maturation.", "mechanism": "Glycopolymer-modified tumor cell vaccines enhance dendritic cell maturation via DC-SIGN, boosting anti-tumor immunity.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584132" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "Multivalent glycan presentation regulates lectin-mediated cell\u2013cell interactions.", "mechanism": "Synthetic glycopolymers on cell surfaces interact with C-type lectins, modulating immune responses.", "protein": "C-type lectins", "relationship_type": "protective", "source_pmcid": "PMC12584132" }, { "confidence": "medium", "disease": "Tumor progression", "glycan_involvement": "Surface glycosylation alters selectin-mediated cell adhesion.", "mechanism": "Glycopolymer engineering can modulate E-selectin interactions, potentially affecting tumor cell adhesion and metastasis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12584132" }, { "confidence": "high", "disease": "Tumor progression", "glycan_involvement": "Glycopolymer-modified T cells preferentially bind Glut1-high cancer cells.", "mechanism": "Glut1 overexpression marks cancer cells for targeted immune cell binding.", "protein": "Glut1", "relationship_type": "biomarker", "source_pmcid": "PMC12584132" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "Glycopolymer modification increases DC-SIGN ligand density on cell surfaces.", "mechanism": "DC-SIGN-mediated recognition of glycosylated antigens enhances dendritic cell activation.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584132" }, { "confidence": "medium", "disease": "Impaired tissue regeneration", "glycan_involvement": "In vivo glycosylation via SYC modulates tissue glycan patterns.", "mechanism": "Altered glycan composition on zebrafish cell membranes affects tissue development and regeneration.", "protein": "Glycan receptors (general)", "relationship_type": "causal", "source_pmcid": "PMC12584132" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "LAMA2 is a glycoprotein; proper glycosylation is required for laminin-211 function.", "mechanism": "Loss-of-function mutations in LAMA2 disrupt basement membrane assembly in muscle, leading to CMD.", "protein": "LAMA2 (laminin alpha-2)", "relationship_type": "causal", "source_pmcid": "PMC12584270" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "Laminin-211 is a glycoprotein; glycosylation affects its assembly and interaction with other ECM proteins.", "mechanism": "Deficiency or absence of laminin-211 impairs muscle fiber stability and basement membrane integrity.", "protein": "Laminin-211 (merosin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Glycosylation status may modulate severity of phenotype.", "mechanism": "Mild mutations in LAMA2 can cause late-onset LGMD phenotype.", "protein": "LAMA2 (laminin alpha-2)", "relationship_type": "causal", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "FKRP mediates O-mannosyl glycosylation of dystroglycan and possibly affects laminin binding.", "mechanism": "FKRP is involved in glycosylation of ECM proteins; its interaction with LAMA2 may influence CMD severity.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "modifier", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "O-mannosyl glycosylation is critical for ECM interactions.", "mechanism": "POMGNT1 participates in O-mannosyl glycosylation of alpha-dystroglycan, modulating laminin-dystroglycan binding.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "modifier", "source_pmcid": "PMC12584270" }, { "confidence": "high", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "Glycosylation of dystroglycan is essential for laminin binding.", "mechanism": "Dystroglycan binds laminin-211; glycosylation defects impair this interaction, exacerbating CMD.", "protein": "DAG1 (dystroglycan)", "relationship_type": "modifier", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "Merosin-deficient congenital muscular dystrophy (CMD)", "glycan_involvement": "SGCA is a glycoprotein; glycosylation may affect complex stability.", "mechanism": "SGCA is part of the dystrophin-glycoprotein complex; interacts with LAMA2 for sarcolemmal integrity.", "protein": "SGCA (alpha-sarcoglycan)", "relationship_type": "modifier", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "Peripheral motor neuropathy", "glycan_involvement": "Glycosylation required for proper ECM assembly in nerves.", "mechanism": "LAMA2 deficiency affects Schwann cell basement membrane, leading to neuropathy.", "protein": "LAMA2 (laminin alpha-2)", "relationship_type": "causal", "source_pmcid": "PMC12584270" }, { "confidence": "low", "disease": "Epilepsy/seizure", "glycan_involvement": "Glycosylation may affect CNS basement membrane interactions.", "mechanism": "LAMA2 expressed in astrocytes and pericytes; deficiency may contribute to neurological symptoms.", "protein": "LAMA2 (laminin alpha-2)", "relationship_type": "modifier", "source_pmcid": "PMC12584270" }, { "confidence": "medium", "disease": "White matter changes (brain MRI)", "glycan_involvement": "Glycosylation status may influence CNS basement membrane stability.", "mechanism": "LAMA2 deficiency disrupts basement membrane in brain capillaries, leading to white matter anomalies.", "protein": "LAMA2 (laminin alpha-2)", "relationship_type": "causal", "source_pmcid": "PMC12584270" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "Defective O-mannosylation of \u03b1-dystroglycan", "mechanism": "Biallelic pathogenic variants in FKTN impair glycosylation of \u03b1-dystroglycan, leading to FCMD.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy (FCMD)", "glycan_involvement": "O-mannosylation required for receptor function", "mechanism": "Hypoglycosylation of \u03b1-dystroglycan disrupts its function in muscle and neural tissues.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "medium", "disease": "High myopia", "glycan_involvement": "Impaired O-glycosylation of \u03b1-dystroglycan in retina", "mechanism": "FKTN variants lead to \u03b1-dystroglycan hypoglycosylation, affecting ocular development and resulting in high myopia.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "medium", "disease": "Optic disc abnormalities", "glycan_involvement": "Defective O-mannosylation impacts optic nerve structure", "mechanism": "FKTN mutations cause abnormal glycosylation of \u03b1-dystroglycan, leading to optic nerve hypoplasia/atrophy.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "medium", "disease": "Retinal detachment", "glycan_involvement": "Disrupted glycosylation impairs retinal basement membrane integrity", "mechanism": "Compound heterozygous FKTN variants predispose to severe retinal dysgenesis and detachment.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "medium", "disease": "Persistent fetal vasculature (PFV)", "glycan_involvement": "Defective \u03b1-dystroglycan glycosylation affects ocular vascular remodeling", "mechanism": "FKTN variants with RT insertion and splice-site mutations are associated with PFV.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "low", "disease": "Strabismus", "glycan_involvement": "Impaired glycosylation of \u03b1-dystroglycan in extraocular muscles", "mechanism": "FKTN mutations disrupt neuromuscular and ocular development, leading to strabismus.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "low", "disease": "Nystagmus", "glycan_involvement": "Disrupted O-glycosylation in neural retina", "mechanism": "FKTN-related glycosylation defects may affect neural circuits controlling eye movement.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "low", "disease": "Peripheral pigmentary degeneration", "glycan_involvement": "Defective \u03b1-dystroglycan glycosylation in RPE", "mechanism": "FKTN variants cause RPE migration/proliferation due to abnormal glycosylation.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "low", "disease": "Peripapillary fibrotic membrane", "glycan_involvement": "Impaired glycosylation affects ocular vascular homeostasis", "mechanism": "FKTN mutations may promote abnormal neovascular remodeling and gliosis.", "protein": "Fukutin (FKTN)", "protein_enriched": { "function": "Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across m", "gene_name": "SLC25A10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBX3" }, "relationship_type": "causal", "source_pmcid": "PMC12584371" }, { "confidence": "high", "disease": "Lower respiratory tract infection", "glycan_involvement": "Glycosylation sites modulate antigenic presentation and immune recognition.", "mechanism": "Mediates viral attachment to host epithelial cells, facilitating infection.", "protein": "G protein", "relationship_type": "causal", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Severe acute respiratory infection", "glycan_involvement": "Glycosylation changes may mask immunodominant epitopes, influencing severity.", "mechanism": "Specific substitutions (e.g., P71L, H90Y, I134K, S243I) associated with severe disease in children.", "protein": "G protein", "relationship_type": "biomarker", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Gain/loss of glycosylation sites alters epitope exposure.", "mechanism": "Accumulation of substitutions and glycan modifications enables escape from host antibodies.", "protein": "G protein", "relationship_type": "causal", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Reduced vaccine/antibody effectiveness", "glycan_involvement": "New glycosylation sites may shield vaccine-targeted epitopes.", "mechanism": "Antigenic variability and glycosylation changes reduce neutralizing antibody binding.", "protein": "G protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Lower respiratory tract infection", "glycan_involvement": "N-glycosylation and O-glycosylation may affect immune recognition.", "mechanism": "Facilitates viral fusion and entry into host cells.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "causal", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Reduced vaccine/antibody effectiveness", "glycan_involvement": "Loss/gain of glycosylation sites may alter epitope accessibility.", "mechanism": "Substitutions (K272N, S276N) in antigenic site II impair palivizumab neutralization.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584621" }, { "confidence": "medium", "disease": "Immune evasion", "glycan_involvement": "Predicted O-glycosylation sites may contribute to epitope masking.", "mechanism": "Amino acid changes and glycan modifications shield neutralizing epitopes.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "causal", "source_pmcid": "PMC12584621" }, { "confidence": "medium", "disease": "Reduced vaccine/antibody effectiveness", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Substitutions in RdRp and connector domains may affect sensitivity to antivirals.", "protein": "L protein", "protein_enriched": { "function": "Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-meth", "gene_name": "PB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03428" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12584621" }, { "confidence": "medium", "disease": "Hospitalization due to RSV", "glycan_involvement": "Glycosylation changes may influence virulence.", "mechanism": "Dominant clade (A.D.1.6) associated with most hospitalizations.", "protein": "G protein", "relationship_type": "biomarker", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Reduced vaccine/antibody effectiveness", "glycan_involvement": "No glycosylation changes affecting these epitopes.", "mechanism": "Vaccine-targeted epitopes (S155C, S190F, V207L, S290C) remain conserved despite other substitutions.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "protective", "source_pmcid": "PMC12584621" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "\u03b2-dystroglycan is heavily glycosylated; glycosylation is essential for its interaction with extracellular matrix and stability.", "mechanism": "Deficiency linked to increased susceptibility to contraction-induced injury and sarcolemmal fragility.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Exercise-induced muscle damage (EIMD)", "glycan_involvement": "Glycosylation status affects \u03b2-dystroglycan's function in membrane stability.", "mechanism": "Decreased protein content post-EPS correlates with muscle damage.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Disuse atrophy", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Loss of desmin required for myofibril disassembly and atrophy.", "protein": "desmin", "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "high", "disease": "Disuse atrophy", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Calpain 3 activation leads to sarcomeric degradation and muscle atrophy.", "protein": "calpain 3", "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "high", "disease": "Muscular dystrophy", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Mutations or dysregulation cause impaired muscle repair and increased fragility.", "protein": "calpain 3", "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Late-onset Pompe disease", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "BNIP3 overexpression linked to myotube atrophy; activated by AKT-mTOR pathway inhibition.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "BNIP3-mediated mitophagy clears dysfunctional mitochondria, relevant in metabolic disease.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation critical for ECM interactions.", "mechanism": "Myogenic progenitor cells inhibit excess collagen deposition via paracrine signaling; \u03b2-dystroglycan involved in ECM stability.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "protective", "source_pmcid": "PMC12586710" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Altered glycosylation may contribute to age-related decline.", "mechanism": "Decline in \u03b2-dystroglycan content and activity correlates with age-related muscle loss.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12586710" }, { "confidence": "medium", "disease": "Exercise-induced muscle damage (EIMD)", "glycan_involvement": "Therapeutic modulation of glycosylation could enhance function.", "mechanism": "Stabilizing \u03b2-dystroglycan may reduce membrane permeability and CK leakage post-damage.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12586710" }, { "confidence": "high", "disease": "ETEC-induced diarrhea", "glycan_involvement": "O-glycosylation critical for mucin barrier function.", "mechanism": "Upregulation of MUC2 enhances mucosal barrier, reducing ETEC adhesion and diarrhea.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "medium", "disease": "Colonic barrier dysfunction", "glycan_involvement": "N-glycosylation affects transporter stability and localization.", "mechanism": "Increased P-glycoprotein expression improves chemical barrier, limiting toxin entry.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "high", "disease": "Colonic barrier dysfunction", "glycan_involvement": "Glycosylation modulates junctional assembly.", "mechanism": "Upregulation of ZO-1 strengthens tight junctions, restoring barrier integrity.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "medium", "disease": "Colonic barrier dysfunction", "glycan_involvement": "Glycosylation influences tight junction function.", "mechanism": "Claudin-1 upregulation improves tight junction sealing, reducing permeability.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "medium", "disease": "Colonic barrier dysfunction", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Occludin upregulation enhances tight junction integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "medium", "disease": "Colonic barrier dysfunction", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "E-cadherin upregulation strengthens cell-cell adhesion, limiting barrier disruption.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Upregulation of CYP3A4 enhances detoxification, reducing inflammatory damage.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "protective", "source_pmcid": "PMC12588845" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for ligand recognition.", "mechanism": "TLR4 activation by ETEC LPS triggers NF-\u03baB pathway and inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12588845" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Potential glycosylation modulates inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation leads to caspase-1 mediated cytokine release.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12588845" }, { "confidence": "high", "disease": "Goblet cell depletion", "glycan_involvement": "O-glycosylation essential for mucin secretion.", "mechanism": "Reduced MUC2 expression marks goblet cell loss and impaired barrier.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12588845" }, { "confidence": "high", "disease": "Aseptic meningitis", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-MOG antibodies trigger immune-mediated inflammation of the meninges, leading to aseptic meningitis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12589052" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG influences immune recognition.", "mechanism": "Anti-MOG antibodies mediate CNS demyelination and inflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12589052" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation may modulate MOG antigenicity.", "mechanism": "Anti-MOG antibodies cause inflammation and demyelination of the optic nerve.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", 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"G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12589052" }, { "confidence": "high", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may influence therapeutic antibody binding.", "mechanism": "Immunotherapy targeting anti-MOG antibody response leads to clinical remission.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12589052" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may affect persistence of antibody response.", "mechanism": "Persistent MOG-IgG positivity may be associated with disease relapse.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12589052" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "MOG glycosylation may be important for immunogenicity in animal models.", "mechanism": "Experimental autoimmune meningitis can be induced by MOG immunization in mice, supporting pathogenic role.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12589052" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Indirect; glycosylation may affect MOG localization and immune targeting.", "mechanism": "Leptomeningeal enhancement on MRI is associated with MOG antibody-mediated aseptic meningitis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12589052" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and autoantibody binding.", "mechanism": "Autoantibodies target MOG, leading to CNS demyelination and inflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12589681" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation state may influence epitope exposure and antibody recognition.", "mechanism": "Presence of anti-MOG IgG is diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12589681" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation of aquaporin-4 may modulate immune recognition.", "mechanism": "Autoantibodies against aquaporin-4 cause astrocyte damage and demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12589681" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Altered glycosylation may affect immune response specificity.", "mechanism": "Anti-MOG antibodies are rare in MS but may indicate atypical demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12589681" }, { "confidence": "high", "disease": "Newcastle disease", "glycan_involvement": "N-glycosylation at multiple sites modulates fusogenicity, replication, and pathogenicity.", "mechanism": "F glycoprotein mediates viral entry, fusion, and spread; its cleavage site motif determines NDV virulence and pathotype.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "Newcastle disease", "glycan_involvement": "N-glycosylation and O-glycosylation affect folding, stability, receptor binding, and F-HN interaction.", "mechanism": "HN glycoprotein mediates viral attachment, receptor binding, and fusion promotion; influences tissue tropism and virulence.", "protein": "HN glycoprotein", "protein_enriched": { "function": "By degrading DNA that enters the cell, plays a role in the competence of cells to be transformed. Degrades both double-stranded, linear and covalently closed circular DNA", "gene_name": "nucA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12667" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "NDV-induced tissue tropism alteration", "glycan_involvement": "N-glycosylation at N447 increases virulence and syncytium formation.", "mechanism": "F cleavage site motif (polybasic vs monobasic) determines ability to replicate in multiple tissues.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "NDV-induced tissue tropism alteration", "glycan_involvement": "N-glycosylation in stalk domain blocks F interaction, affecting fusion and tropism.", "mechanism": "HN gene exchange alters tissue tropism and virulence in chimeric NDVs.", "protein": "HN glycoprotein", "protein_enriched": { "function": "By degrading DNA that enters the cell, plays a role in the competence of cells to be transformed. Degrades both double-stranded, linear and covalently closed circular DNA", "gene_name": "nucA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12667" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "medium", "disease": "NDV-induced thermostability phenotype", "glycan_involvement": "N-glycosylation sites contribute to protein stability.", "mechanism": "F glycoprotein domains and glycosylation modulate thermostability and viral phenotype.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "medium", "disease": "NDV-induced thermostability phenotype", "glycan_involvement": "N-glycosylation impacts folding and stability.", "mechanism": "HN glycoprotein length and glycosylation affect thermostability and viral phenotype.", "protein": "HN glycoprotein", "protein_enriched": { "function": "By degrading DNA that enters the cell, plays a role in the competence of cells to be transformed. Degrades both double-stranded, linear and covalently closed circular DNA", "gene_name": "nucA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12667" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "NDV-induced syncytium formation", "glycan_involvement": "N-glycosylation at N447 enhances fusion activity.", "mechanism": "Mutations at N447 increase syncytium formation and virulence.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "medium", "disease": "NDV-induced syncytium formation", "glycan_involvement": "O-glycosylation at T71 may influence oligomerization and fusion kinetics.", "mechanism": "HN stalk and head domains regulate fusion-promoting activity and syncytium formation.", "protein": "HN glycoprotein", "protein_enriched": { "function": "By degrading DNA that enters the cell, plays a role in the competence of cells to be transformed. Degrades both double-stranded, linear and covalently closed circular DNA", "gene_name": "nucA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12667" }, "relationship_type": "causal", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "Newcastle disease", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "F glycoprotein is a major antigen inducing neutralizing antibodies; target for broad-spectrum antivirals.", "protein": "F glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03420" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "Newcastle disease", "glycan_involvement": "Glycosylation modulates antigenic sites and drug binding.", "mechanism": "HN glycoprotein is a major antigen and target for neutralizing antibodies and antiviral drugs.", "protein": "HN glycoprotein", "protein_enriched": { "function": "By degrading DNA that enters the cell, plays a role in the competence of cells to be transformed. Degrades both double-stranded, linear and covalently closed circular DNA", "gene_name": "nucA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12667" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12590790" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Specific acidic N-glycans (5_4_0_1-a, 5_4_0_2-a, 5_4_0_2-b) are differentially expressed in RA.", "mechanism": "Altered IgG N-glycan profiles distinguish RA patients from healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12590853" }, { "confidence": "high", "disease": "RA - cold-dampness impeding syndrome (TCM cold pattern)", "glycan_involvement": "Lower levels of disialylated N-glycans (5_4_0_2-a, 5_4_0_2-b) compared to heat pattern.", "mechanism": "Distinct IgG N-glycan signature enables differentiation of cold pattern RA from healthy controls and heat pattern RA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12590853" }, { "confidence": "high", "disease": "RA - dampness-heat impeding syndrome (TCM heat pattern)", "glycan_involvement": "Highest increase in disialylated N-glycans (5_4_0_2-a, 5_4_0_2-b), greatest decrease in monosialylated N-glycan (5_4_0_1-a).", "mechanism": "Distinct IgG N-glycan signature enables differentiation of heat pattern RA from healthy controls and cold pattern RA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12590853" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Absence of terminal galactose/sialic acid exposes GlcNAc, activates complement via MBP.", "mechanism": "Altered IgG glycosylation (reduced galactosylation, increased agalactosylation) promotes autoantibody production and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12590853" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Lower sialylation in IgG N-glycans in RA patients compared to healthy controls.", "mechanism": "Reduced IgG sialylation correlates with increased pro-inflammatory activity and disease severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12590853" }, { "confidence": "medium", "disease": "RA - 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It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12592166" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Integrin glycosylation modulates ligand binding and cell adhesion.", "mechanism": "Upregulation of ITGAV and its ligands (ADAM15, CCN1, VWF, FGF2) in MS suggests enhanced endothelial-astrocyte adhesion and signaling.", "protein": "ITGAV", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12592424" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "NRP2 glycosylation affects semaphorin binding and receptor trafficking.", "mechanism": "NRP2 and its ligand SEMA3F are upregulated in MS, indicating altered semaphorin signaling affecting BBB and remyelination.", "protein": "NRP2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12592424" }, { "confidence": "high", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Altered glycosylation may reduce NRP2 function and ligand interaction.", "mechanism": "NRP2 is downregulated in AD astrocytes; loss of semaphorin-NRP2 signaling impairs neuronal plasticity and memory.", "protein": "NRP2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "SEMA3F glycosylation influences receptor binding and signaling.", "mechanism": "Endothelial-derived SEMA3F upregulation modulates vessel growth and remyelination in MS lesions.", "protein": "SEMA3F", "protein_enriched": { "function": "May play a role in cell motility and cell adhesion", "gene_name": "SEMA3F", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23294PN", "G25418HZ", "G62765YT", "G27058EU", "G40926MX", "G59536GA", "G83460ZZ", "G43417UB" ], "uniprot_id": "Q13275" }, "relationship_type": "causal", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Glycosylation affects semaphorin stability and receptor interaction.", "mechanism": "Downregulation of SEMA3B/SEMA3C and NRP2 in AD may impair BBB integrity and neuronal function.", "protein": "SEMA3B/SEMA3C", "relationship_type": "causal", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "VWF glycosylation is critical for multimerization and endothelial interactions.", "mechanism": "Upregulated VWF-ITGAV signaling in MS may reflect vascular activation and BBB dysfunction.", "protein": "VWF", "relationship_type": "biomarker", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "FGF2 glycosylation modulates receptor binding and stability.", "mechanism": "FGF2-ITGAV signaling upregulated in MS, possibly promoting angiogenesis and BBB remodeling.", "protein": "FGF2", "relationship_type": "biomarker", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Neuroinflammation (LPS model, relevance to MS/AD)", "glycan_involvement": "CD44 glycosylation regulates ligand binding and cell migration.", "mechanism": "SPP1-CD44 signaling upregulated after LPS and in astrocytes, indicating astrocyte activation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Cerebral Infarction (Stroke)", "glycan_involvement": "WNT glycosylation required for secretion and receptor interaction.", "mechanism": "WNT10B polymorphisms associated with stroke risk; WNT10B-FZD7 signaling attenuates BBB disruption.", "protein": "WNT10B", "protein_enriched": { "function": "Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-ca", "gene_name": "WNT10B", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O00744" }, "relationship_type": "protective", "source_pmcid": "PMC12592424" }, { "confidence": "medium", "disease": "Neuroinflammation (LPS model, relevance to MS/AD)", "glycan_involvement": "LCN2 glycosylation affects stability and receptor binding.", "mechanism": "LCN2-SLC22A17 signaling upregulated after LPS, indicating endothelial-astrocyte immune communication.", "protein": "LCN2", "relationship_type": "biomarker", "source_pmcid": "PMC12592424" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Autoantibodies are glycosylated; glycan structures may affect immunogenicity.", "mechanism": "Elevated anti-cardiolipin antibody titers are diagnostic and associated with APS.", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12593030" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "N-glycosylation modulates antigenicity and antibody binding.", "mechanism": "Beta-2 glycoprotein I is the main antigenic target for antiphospholipid antibodies, mediating thrombosis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "high", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation may affect antibody effector function and clearance.", "mechanism": "Presence of anti-cardiolipin antibodies increases risk of arterial thrombosis including stent thrombosis.", "protein": "Anti-cardiolipin antibody", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "high", "disease": "Stent thrombosis", "glycan_involvement": "Glycan modifications influence immune complex formation.", "mechanism": "Beta-2 glycoprotein I-antibody complexes promote prothrombotic state leading to stent thrombosis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "medium", "disease": "Coronary artery bypass graft (CABG) failure", "glycan_involvement": "Glycosylation may modulate antibody pathogenicity.", "mechanism": "Elevated anti-cardiolipin antibodies are associated with increased risk of CABG failure.", "protein": "Anti-cardiolipin antibody", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation affects antigen-antibody interactions.", "mechanism": "Beta-2 glycoprotein I-antibody complexes contribute to arterial thrombosis causing stroke in APS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "high", "disease": "Myocardial infarction (MI)", "glycan_involvement": "Troponin is glycosylated; glycosylation may affect stability and detection.", "mechanism": "Elevated troponin levels indicate myocardial injury during stent thrombosis.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12593030" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycan structures modulate immune response.", "mechanism": "Thrombotic events mediated by beta-2 glycoprotein I antibodies can lead to myocardial injury and heart failure.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "medium", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation may affect antibody function.", "mechanism": "Anti-cardiolipin antibodies promote arterial thrombosis leading to ACS.", "protein": "Anti-cardiolipin antibody", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "medium", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "N-glycosylation modulates immune complex formation.", "mechanism": "Beta-2 glycoprotein I-antibody complexes drive thrombo-inflammatory processes in ACS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12593030" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Fucosylated glycan motifs in LPS core are essential for DC-SIGN binding and immune modulation.", "mechanism": "Recognition of fucosylated LPS core oligosaccharides from Phocaeicola vulgatus by DC-SIGN modulates dendritic cell function, promoting anti-inflammatory responses and intestinal homeostasis.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Fucose-calcium coordination in DC-SIGN CRD is critical for ligand binding and immune modulation.", "mechanism": "Synthetic fucosylated glycan epitopes targeting DC-SIGN may be developed as immunomodulators to treat or prevent inflammatory bowel disease.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Synthetic fucosylated oligosaccharides mimic bacterial glycan signatures to engage DC-SIGN.", "mechanism": "Glycomimetic probes based on fucosylated motifs can be designed to modulate DC-SIGN activity, potentially impacting autoimmune disease outcomes.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12593043" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Absence of fucose in LPS core abolishes DC-SIGN binding and anti-inflammatory signaling.", "mechanism": "Loss or alteration of fucosylated LPS motifs reduces DC-SIGN engagement, potentially leading to dysregulated immune responses and increased inflammation.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Galactofuranose acts as a supporting element in glycan conformation for DC-SIGN recognition.", "mechanism": "Peripheral Galactofuranose residues in LPS core modulate the presentation of fucosylated epitopes, enhancing DC-SIGN-mediated immune tolerance.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Specific fucosylated glycan motifs in LPS core are detected by DC-SIGN.", "mechanism": "DC-SIGN recognition of fucosylated LPS motifs may serve as a biomarker for gut immune homeostasis and disease risk.", "protein": "DC-SIGN", "relationship_type": "biomarker", "source_pmcid": "PMC12593043" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Fucose hydroxyl groups coordinate with calcium in DC-SIGN CRD for stable interaction.", "mechanism": "Calcium-dependent binding of fucosylated LPS to DC-SIGN stabilizes tolerogenic dendritic cell responses.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Structural diversity in fucosylated motifs affects DC-SIGN binding.", "mechanism": "Strain-specific variations in LPS glycan structure may influence DC-SIGN engagement and immune outcomes.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12593043" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Synthetic fucosylated ligands designed for DC-SIGN engagement.", "mechanism": "Fucose-based inhibitors targeting DC-SIGN could modulate immune responses in IBD.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12593043" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Fucosylated glycan motifs in commensal LPS are selectively recognized by DC-SIGN.", "mechanism": "DC-SIGN discriminates commensal from pathogenic signals via recognition of fucosylated LPS, maintaining immune equilibrium.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12593043" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type 1T (PGM1-CDG)", "glycan_involvement": "Disrupted N-glycosylation of multiple proteins due to impaired glycan precursor synthesis.", "mechanism": "PGM1 deficiency impairs glycoprotein biosynthesis and energy metabolism.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type 1T (PGM1-CDG)", "glycan_involvement": "Altered N-glycosylation pattern detectable in serum.", "mechanism": "Abnormal glycoform distribution (carbohydrate-deficient transferrin) indicates defective glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "Impaired N-glycosylation affects stability and activity of coagulation proteins.", "mechanism": "Defective glycosylation of coagulation factors impairs their function, leading to abnormal coagulation profiles.", "protein": "Coagulation factors (e.g., prothrombin)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Liver failure/hepatopathy", "glycan_involvement": "Defective glycosylation of hepatic proteins.", "mechanism": "PGM1 deficiency leads to impaired glycoprotein synthesis in hepatocytes, causing liver dysfunction and fibrosis.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "medium", "disease": "Myopathy", "glycan_involvement": "Defective glycosylation of muscle proteins.", "mechanism": "Impaired glycosylation and energy metabolism in muscle tissue leads to hypotonia and elevated creatine kinase.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "medium", "disease": "Developmental delay", "glycan_involvement": "Impaired glycosylation of neural proteins and receptors.", "mechanism": "Defective glycosylation affects neuronal development and function.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Liver failure/hepatopathy", "glycan_involvement": "Altered N-glycosylation in liver-derived transferrin.", "mechanism": "Carbohydrate-deficient transferrin reflects hepatic glycosylation status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "Defective N-glycosylation of plasma proteins.", "mechanism": "PGM1 deficiency impairs glycosylation of coagulation factors, leading to bleeding tendency.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "causal", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type 1T (PGM1-CDG)", "glycan_involvement": "Restores glycan precursor availability for N-glycosylation.", "mechanism": "D-galactose supplementation bypasses glycosylation defect, improving hepatic glycoprotein synthesis.", "protein": "PGM1 (Phosphoglucomutase 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12594020" }, { "confidence": "medium", "disease": "Myopathy", "glycan_involvement": "Indirect; muscle pathology secondary to glycosylation impairment.", "mechanism": "Elevated creatine kinase reflects muscle damage due to glycosylation defect.", "protein": "Creatine kinase", "relationship_type": "biomarker", "source_pmcid": "PMC12594020" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "EGFR is heavily N-glycosylated, affecting ligand binding and signaling.", "mechanism": "EGFR overexpression promotes cell proliferation; S. platensis reduces EGFR protein levels, inhibiting growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "K-ras is prenylated, not glycosylated; glycan involvement is minimal.", "mechanism": "K-ras mutations drive tumorigenesis; S. platensis reduces K-ras protein levels.", "protein": "K-ras", "relationship_type": "causal", "source_pmcid": "PMC12594977" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "ILF3 is a glycoprotein; glycosylation may affect nuclear localization and RNA binding.", "mechanism": "ILF3 upregulation promotes cancer progression; S. platensis binds ILF3, inhibiting its function.", "protein": "ILF3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "MTUS1 acts as tumor suppressor; decreased after S. platensis treatment, possibly reflecting cell cycle arrest.", "protein": "MTUS1", "protein_enriched": { "function": "Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regula", "gene_name": "EPN1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "Q9Y6I3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "P16 loss promotes uncontrolled proliferation; S. platensis decreases P16 protein, possibly via epigenetic modulation.", "protein": "P16 (CDKN2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "BRMS1 upregulation suppresses metastasis; S. platensis increases BRMS1 expression.", "protein": "BRMS1", "protein_enriched": { "function": "Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates express", "gene_name": "BRMS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HCU9" }, "relationship_type": "protective", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "BCL-2 inhibits apoptosis; S. platensis downregulates BCL-2, promoting cell death.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "BAX promotes apoptosis; S. platensis upregulates BAX, enhancing cell death.", "protein": "BAX", "relationship_type": "protective", "source_pmcid": "PMC12594977" }, { "confidence": "low", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SHOX2 downregulation by S. platensis may contribute to anti-proliferative effects.", "protein": "SHOX2", "protein_enriched": { "function": "Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. May promote the assembly of presynaptic RA", "gene_name": "RAD51B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12594977" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Heavily N-glycosylated; glycosylation affects trafficking and function.", "mechanism": "P-glycoprotein mediates drug efflux; S. platensis is a substrate, may affect drug resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12594977" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TIMP-3 is ECM-integrated; glycosylation may affect ECM retention and A\u03b2 aggregate binding.", "mechanism": "TIMP-3 inhibits ADAM10, promoting APP to A\u03b2 conversion; levels altered in CSF and brain, correlating with disease stage and cognitive decline.", "protein": "TIMP-3", "protein_enriched": { "function": "Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metallopr", "gene_name": "TIMP3", "glycan_count": 12, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G27058EU", "G31852PQ", "G41071NU", "G43669FQ", "G45395BF", "G51653BI", "G61256FT", "G62765YT", "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P35625" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12595144" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and ECM interactions.", "mechanism": "Decreased CSF TIMP-1 and increased MMP-9 activity are associated with vascular damage and cognitive decline.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12595144" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Secreted glycoprotein; glycosylation may modulate secretion and activity.", "mechanism": "Elevated in substantia nigra in response to \u03b1-synuclein aggregation; inhibits MMP-9, reducing BBB disruption and \u03b1-synuclein spreading.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12595144" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "ECM integration may be glycan-dependent.", "mechanism": "Decreased TIMP-3 in substantia nigra with increased MMP-7/9; 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high expression correlates with better prognosis.", "protein": "TIMP-3", "protein_enriched": { "function": "Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metallopr", "gene_name": "TIMP3", "glycan_count": 12, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT", "G27058EU", "G31852PQ", "G41071NU", "G43669FQ", "G45395BF", "G51653BI", "G61256FT", "G62765YT", "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P35625" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12595144" }, { "confidence": "high", "disease": "Cognitive decline/aging", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect receptor interactions.", "mechanism": "Promotes neuronal differentiation and plasticity via \u03b13\u03b21 integrin signaling and ECM modulation; decreased expression impairs neurogenesis and memory.", "protein": "TIMP-2", "protein_enriched": { "function": "Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10", "gene_name": "TIMP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16035" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12595144" }, { "confidence": "medium", "disease": "Huntington's disease", "glycan_involvement": "Secreted glycoprotein.", "mechanism": "Elevated in striatum correlates with mHTT-induced astrocyte activation.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12595144" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Secreted glycoprotein.", "mechanism": "Enhances immune infiltration by recruiting CD4+ T cells; high expression correlates with better prognosis.", "protein": "TIMP-4", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12595144" }, { "confidence": "high", "disease": "Intervertebral Disk Degeneration (IVDD)", "glycan_involvement": "BTN1A1 is a glycoprotein; glycosylation may affect immune modulation and protein stability.", "mechanism": "Regulates T cell immune responses, modulates immune inflammation in intervertebral disc.", "protein": "BTN1A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12595932" }, { "confidence": "high", "disease": "Intervertebral Disk Degeneration (IVDD)", "glycan_involvement": "EIF2AK3 is glycosylated; glycosylation may regulate ER localization and stress signaling.", "mechanism": "Mediates endoplasmic reticulum stress signaling, influences nucleus pulposus degeneration.", "protein": "EIF2AK3", "protein_enriched": { "function": "Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein", "gene_name": "EIF2AK3", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65184UU", "G57321FI", "G49108TO" ], "uniprot_id": "Q9NZJ5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12595932" }, { "confidence": "high", "disease": "Sciatica", "glycan_involvement": "DAG1 is heavily glycosylated; glycosylation is essential for ECM binding and nerve function.", "mechanism": "Maintains peripheral nerve myelin and stabilizes Na+ channels; mediates ECM-neuron interactions.", "protein": "DAG1", "relationship_type": "protective", "source_pmcid": "PMC12595932" }, { "confidence": "medium", "disease": "Sciatica", "glycan_involvement": "SUMO2 is not a classical glycoprotein but may modify glycoproteins via SUMOylation.", "mechanism": "SUMOylation regulates ion channels involved in pain signaling.", "protein": "SUMO2", "protein_enriched": { "function": "Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by", "gene_name": "SUMO2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61956" }, "relationship_type": "protective", "source_pmcid": "PMC12595932" }, { "confidence": "high", "disease": "Sciatica", "glycan_involvement": "GPX1 is glycosylated; glycosylation may affect enzyme activity and cellular localization.", "mechanism": "Reduces oxidative stress, protects disc cells from damage.", "protein": "GPX1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12595932" }, { "confidence": "high", "disease": "Low Back Pain (LBP)", "glycan_involvement": "P2RY13 is a GPCR; glycosylation may influence receptor trafficking and signaling.", "mechanism": "Regulates neurotransmitter release and pain transmission.", "protein": "P2RY13", "protein_enriched": { "function": "Odorant receptor", "gene_name": "OR4A15", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8NGL6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12595932" }, { "confidence": "medium", "disease": "Intervertebral Disk Degeneration (IVDD)", "glycan_involvement": "CAPN10 may be glycosylated; glycosylation could affect protease activity.", "mechanism": "Influences metabolic homeostasis, links immunometabolic changes to disc degeneration.", "protein": "CAPN10", "relationship_type": "causal", "source_pmcid": "PMC12595932" }, { "confidence": "medium", "disease": "Intervertebral Disk Degeneration (IVDD)", "glycan_involvement": "AKR1C2 may be glycosylated; glycosylation could modulate enzyme stability.", "mechanism": "Degrades lipid peroxides, counteracts ferroptosis in disc cells.", "protein": "AKR1C2", "relationship_type": "protective", "source_pmcid": "PMC12595932" }, { "confidence": "medium", "disease": "Sciatica", "glycan_involvement": "NT5C may be glycosylated; glycosylation could influence enzyme activity.", "mechanism": "Regulates AMP/ATP ratio, affects glucose uptake and lipid oxidation in disc cells.", "protein": "NT5C", "protein_enriched": { "function": "Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705). In ", "gene_name": "NT5C2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49902" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12595932" }, { "confidence": "low", "disease": "Low Back Pain (LBP)", "glycan_involvement": "FGL2 is a glycoprotein; glycosylation is important for immune function.", "mechanism": "Involved in immune regulation and inflammation.", "protein": "FGL2", "protein_enriched": { "function": "May play a role in physiologic lymphocyte functions at mucosal sites", "gene_name": "FGL2", "glycan_count": 125, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G53434XO", "G29068FM", "G05049YU", "G05962QB", "G07246CJ", "G13694XX", "G16125XL", "G20528HD", "G27058EU", "G31852PQ", "G32788FZ", "G34617SM", "G34989PA", "G35541EV", "G39471UU", "G41071NU", "G44753VC", "G45395BF", "G46691LC", "G47748JZ", "G48414YA", "G49589RB", "G55132BD", "G57776ZS", "G62765YT", "G65184UU", "G69521XL", "G70441OD", "G71463BG", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G81263BG", "G82443XX", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92406TI", "G93718GY", "G94470IW", "G95046LV", "G02815KT", "G10486CT", "G28541PG", "G57776ZU", "G84349RE", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G08290VR", "G08918WF", "G11314AS", "G18647XP", "G23453IV", "G23719VF", "G28681TP", "G29299MO", "G35029YA", "G37399XV", "G39446WN", "G40926MX", "G41247ZX", "G42124LM", "G43223CG", "G45504EY", "G47644PP", "G59626AS", "G59924QI", "G60033FS", "G63041LO", "G64409MC", "G72787SB", "G83646BJ", "G85269DF", "G86182NS", "G88891KO", "G90575OW", "G90734RJ", "G92050GC", "G92275SC", "G95865ZB", "G96091TT", "G01485JJ", "G02886BB", "G04657PL", "G04854VP", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11629QQ", "G14972EH", "G17208MA", "G20706XG", "G23863VK", "G27126ED", "G37881RL", "G40574BA", "G47950XN", "G52527GH", "G58954YZ", "G59536GA", "G61256FT", "G65000LJ", "G66621EA", "G70223PD", "G70232NH", "G70619PT", "G70822IO", "G72747WU", "G75418YA", "G75983OB", "G77669RF", "G83460ZZ", "G84452RH", "G87389XI", "G89045VA", "G90382BL", "G92135MA", "G92551JA" ], "uniprot_id": "Q14314" }, "relationship_type": "candidate biomarker", "source_pmcid": "PMC12595932" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "GlcNAc modifications on WTA are key antibody epitopes.", "mechanism": "WTA-specific antibodies promote opsonization and phagocytosis of S. aureus.", "protein": "Wall Teichoic Acid (WTA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Methicillin-resistant Staphylococcus aureus (MRSA)", "glycan_involvement": "Targeting \u03b2- or \u03b1-GlcNAc on WTA.", "mechanism": "Anti-WTA monoclonal antibodies reduce MRSA persistence in mouse models.", "protein": "Wall Teichoic Acid (WTA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Antibody recognition of WTA glycoforms is protective.", "mechanism": "Low WTA-specific IgM correlates with increased mortality and impaired opsonization in S. aureus bacteremia.", "protein": "Wall Teichoic Acid (WTA)", "relationship_type": "protective", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "GlcNAc and polyrhamnose (PR) modifications are antibody targets.", "mechanism": "Anti-GAC monoclonal antibodies promote complement deposition and opsonization of S. pyogenes.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12596258" }, { "confidence": "medium", "disease": "Rheumatic heart disease", "glycan_involvement": "GlcNAc epitope is implicated in molecular mimicry.", "mechanism": "Antibody cross-reactivity to GAC-GlcNAc and human GlcNAc may contribute to pathogenesis.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "causal", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Enzyme controls WTA glycoform and antibody epitope presentation.", "mechanism": "TarS mediates \u03b2-1,4-GlcNAc modification of WTA, affecting immune recognition.", "protein": "TarS glycosyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Enzyme determines WTA glycan stereochemistry.", "mechanism": "TarM mediates \u03b1-1,4-GlcNAc modification of WTA, influencing antibody specificity.", "protein": "TarM glycosyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Enzyme creates distinct WTA glycoforms.", "mechanism": "TarP mediates \u03b2-1,3-GlcNAc modification of WTA, affecting immune recognition.", "protein": "TarP glycosyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "Repeating GlcNAc and PR units are diagnostic/vaccine targets.", "mechanism": "GAC is used for rapid diagnostic tests and vaccine antigen.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "biomarker", "source_pmcid": "PMC12596258" }, { "confidence": "medium", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "PR backbone is non-mammalian and less likely to induce autoimmunity.", "mechanism": "Anti-PR backbone antibodies may provide safer targeting, avoiding GlcNAc cross-reactivity.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12596258" }, { "confidence": "high", "disease": "Breast cancer (BC)", "glycan_involvement": "Increased sialylation and altered N-glycan structures on IgG detected by ABA and SSA lectins.", "mechanism": "Altered glycosylation patterns detected by lectin microarray distinguish BC from controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "high", "disease": "Breast cancer (BC)", "glycan_involvement": "Lower HHL, MNA-M, DSL, IRA binding in HR+; higher Jacalin, AIA, MNA-M, HHL, NPL, GNL, SBA in HER2+.", "mechanism": "Subtype-specific IgG glycosylation patterns differentiate HR+ vs HR\u2212 and HER2+ vs HER2\u2212 BC.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Increased sialylation at Asn162 N-glycan site.", "mechanism": "Sialylated N-glycosylation at Asn162 associated with immune suppression and invasiveness.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "high", "disease": "Breast cancer (BC)", "glycan_involvement": "Highly glycosylated O-glycan epitope.", "mechanism": "CA15-3 (MUC1 epitope) is a clinical serum biomarker for BC diagnosis and monitoring.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "medium", "disease": "Breast cancer (BC)", "glycan_involvement": "Altered glycosylation in cancer.", "mechanism": "CEA is a glycoprotein used as a serum biomarker in BC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "medium", "disease": "Breast cancer (BC)", "glycan_involvement": "Altered glycosylation/lectin domain involvement.", "mechanism": "CLEC3A expression in tumor extracellular matrix correlates with aggressive phenotypes.", "protein": "CLEC3A", "protein_enriched": { "function": "Involved in control of cellular proliferation. Onconcogenic modifier contributing to the tumor suppressor function of DNMT3B", "gene_name": "MENT", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G29068FM", "G53434XO" ], "uniprot_id": "Q9BUN1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "medium", "disease": "Breast cancer (BC)", "glycan_involvement": "Binds \u03b2-galactoside glycans; altered glycosylation affects function.", "mechanism": "Altered galectin-3 expression correlates with lymph node metastasis and poor prognosis.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "low", "disease": "Breast cancer (BC)", "glycan_involvement": "Binds \u03b2-galactoside glycans.", "mechanism": "Expression linked to BC prognosis.", "protein": "Galectin-7", "protein_enriched": { "function": "Could be involved in cell-cell and/or cell-matrix interactions necessary for normal growth control. Pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c rel", "gene_name": "LGALS7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47929" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "low", "disease": "Breast cancer (BC)", "glycan_involvement": "Binds specific glycan structures on cell surface.", "mechanism": "Contributes to increased BC invasion through extracellular matrix.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "causal", "source_pmcid": "PMC12596431" }, { "confidence": "medium", "disease": "Breast cancer (BC)", "glycan_involvement": "Increased branching and sialylation of N-glycans on IgG Fc.", "mechanism": "Highly branched N-glycans on IgG may indicate early BC and altered immune environment.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12596431" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Albumin glycosylation affects stability and antioxidant function; altered glycosylation may reduce protective effects.", "mechanism": "Low serum albumin predicts increased risk and severity of AHF; hypoalbuminemia worsens myocardial edema, congestion, and diuretic resistance.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "high", "disease": "Hip Fracture (postoperative)", "glycan_involvement": "Glycosylation status may influence albumin's half-life and function in wound healing.", "mechanism": "Low albumin levels indicate poor nutritional status and predict higher risk of postoperative complications, including AHF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Glycosylation may be altered in malnutrition, affecting albumin's transport and stability.", "mechanism": "Hypoalbuminemia is both a marker and driver of malnutrition, forming a vicious cycle that worsens outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Cirrhosis alters glycosylation patterns of albumin, impacting its function.", "mechanism": "Cirrhosis leads to reduced albumin synthesis and altered glycosylation, increasing risk of AHF and other complications.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "BNP is glycosylated; glycan modifications may affect its stability and clearance.", "mechanism": "Elevated BNP is diagnostic for AHF; reflects cardiac stress and ventricular dysfunction.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Glycosylation affects NT-proBNP's plasma half-life and immunoreactivity.", "mechanism": "Elevated NT-proBNP is diagnostic for AHF, especially in older adults; correlates with severity.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Cerebrovascular Disease", "glycan_involvement": "Altered glycosylation may affect albumin's neuroprotective properties.", "mechanism": "Low albumin may indicate poor prognosis and increased risk of cardiac complications post-stroke.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Proper glycosylation enhances albumin's protective functions.", "mechanism": "Normal albumin levels exert antioxidant and anti-inflammatory effects, protecting against AHF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Hip Fracture (postoperative)", "glycan_involvement": "Glycosylation may modulate BNP's diagnostic accuracy.", "mechanism": "BNP elevation post-surgery may indicate early cardiac stress and risk for AHF.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12596889" }, { "confidence": "medium", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Therapeutic albumin glycosylation status may affect efficacy.", "mechanism": "Albumin infusion is used to correct hypoalbuminemia and may reduce risk of postoperative AHF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12596889" }, { "confidence": "high", "disease": "Emphysema", "glycan_involvement": "Decreased complex-type bi-antennary N-glycans reduce Z-AAT stability and function.", "mechanism": "Reduced anti-elastase activity leads to unchecked neutrophil elastase, causing lung tissue destruction.", "protein": "Z-AAT", "relationship_type": "causal", "source_pmcid": "PMC12597287" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Altered N-glycosylation impairs secretion and anti-protease function.", "mechanism": "Low and dysfunctional Z-AAT fails to inhibit proteases, promoting chronic airway inflammation.", "protein": "Z-AAT", "relationship_type": "causal", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Bronchiectasis", "glycan_involvement": "Reduced N-glycan maturation may decrease circulating Z-AAT levels.", "mechanism": "Impaired Z-AAT function leads to chronic neutrophilic inflammation and airway damage.", "protein": "Z-AAT", "relationship_type": "causal", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Altered glycosylation may further reduce Z-AAT anti-inflammatory capacity.", "mechanism": "Deficient Z-AAT fails to control neutrophil proteases, amplifying skin inflammation.", "protein": "Z-AAT", "relationship_type": "causal", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation defects may reduce polymer secretion, affecting liver disease risk.", "mechanism": "Intracellular polymer accumulation in hepatocytes leads to liver injury.", "protein": "Z-AAT", "relationship_type": "causal", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Emphysema", "glycan_involvement": "Not specified.", "mechanism": "Elevated plasma PAI-1 reflects ongoing inflammation and tissue remodeling.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Emphysema", "glycan_involvement": "Not specified.", "mechanism": "High MPO indicates neutrophil activation and chronic lung inflammation.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Emphysema", "glycan_involvement": "Not specified.", "mechanism": "Elevated NGAL is associated with neutrophil-driven tissue injury.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12597287" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Not specified.", "mechanism": "Decreased fetuin-A reflects impaired hepatic function and chronic inflammation.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12597287" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Altered glycosylation may further reduce protective effects.", "mechanism": "Normal AAT may protect against airway inflammation; Z-AAT deficiency increases risk.", "protein": "Z-AAT", "relationship_type": "protective", "source_pmcid": "PMC12597287" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "ApoE is N-glycosylated, which may affect receptor binding and clearance functions.", "mechanism": "APOE4 allele increases risk of late-onset AD via impaired A\u03b2 clearance, tau phosphorylation, neuroinflammation, and vascular dysfunction.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Chemotherapy-related cognitive impairment (CRCI)", "glycan_involvement": "N-glycosylation may modulate ApoE interactions with lipoprotein receptors.", "mechanism": "APOE4 allele increases risk and severity of CRCI; APOE2 is protective.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Tau is O-glycosylated; glycosylation may modulate aggregation and phosphorylation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, correlating with cognitive decline.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12597692" }, { "confidence": "medium", "disease": "Chemotherapy-related cognitive impairment (CRCI)", "glycan_involvement": "O-glycosylation may influence tau aggregation in CRCI as in AD.", "mechanism": "Chemotherapy increases CSF tau; tau pathology correlates with cognitive impairment.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation affects processing and A\u03b2 production.", "mechanism": "APP cleavage produces A\u03b2 plaques, a hallmark of AD.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12597692" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "N-glycosylation is essential for P-glycoprotein folding and function.", "mechanism": "P-glycoprotein 1 mediates A\u03b2 clearance across BBB; reduced activity in AD may increase brain A\u03b2.", "protein": "P-glycoprotein 1 (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12597692" }, { "confidence": "medium", "disease": "Chemotherapy-related cognitive impairment (CRCI)", "glycan_involvement": "N-glycosylation modulates substrate specificity and BBB transport.", "mechanism": "P-glycoprotein 1 limits brain entry of chemotherapeutics; reduced activity may increase neurotoxicity.", "protein": "P-glycoprotein 1 (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "BDNF is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Reduced BDNF in AD impairs synaptic plasticity and neurogenesis; increasing BDNF is neuroprotective.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Chemotherapy-related cognitive impairment (CRCI)", "glycan_involvement": "Glycosylation modulates BDNF stability and function.", "mechanism": "Chemotherapy reduces BDNF, contributing to cognitive deficits; BDNF agonists improve cognition.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12597692" }, { "confidence": "medium", "disease": "Alzheimer disease (AD)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects its interactions with cells and matrix.", "mechanism": "Fibrinogen leakage into brain parenchyma activates microglia and promotes synapse loss.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12597692" }, { "confidence": "high", "disease": "Bilateral lens dislocation (luxation)", "glycan_involvement": "Fibrillin-1 is a glycoprotein; glycosylation affects ECM stability.", "mechanism": "Altered synthesis/degradation of fibrillin-1 weakens ciliary zonule, leading to lens dislocation.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "high", "disease": "Bilateral lens dislocation (luxation)", "glycan_involvement": "IGF-1 glycosylation affects receptor binding and stability.", "mechanism": "Chronic IGF-1 excess regulates fibrillin-1 synthesis/degradation via PI3K/Akt pathway, weakening lens suspensory apparatus.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Bilateral lens dislocation (luxation)", "glycan_involvement": "Receptor glycosylation modulates ligand binding and signaling.", "mechanism": "IGF-1R activation in ocular tissues mediates antiapoptotic/proliferative effects, impacting lens and zonule integrity.", "protein": "IGF-1 receptor", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "high", "disease": "Acromegaly", "glycan_involvement": "GH glycosylation influences secretion and activity.", "mechanism": "GH hypersecretion is diagnostic and drives systemic effects.", "protein": "GH", "relationship_type": "biomarker", "source_pmcid": "PMC12597749" }, { "confidence": "high", "disease": "Acromegaly", "glycan_involvement": "Glycosylation affects IGF-1 stability and bioavailability.", "mechanism": "Elevated IGF-1 reflects GH excess and disease activity.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect IGF-1 receptor interactions.", "mechanism": "Chronic IGF-1 excess induces insulin resistance, contributing to secondary diabetes.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Bilateral lens dislocation (luxation)", "glycan_involvement": "MMPs are glycoproteins; glycosylation modulates activity.", "mechanism": "MMPs degrade fibrillin-1 in ECM, weakening zonular fibers.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Acromegaly", "glycan_involvement": "Glycosylation critical for ECM assembly and function.", "mechanism": "Altered fibrillin-1 metabolism in ECM contributes to tissue overgrowth and complications.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation may affect IGF-1 bioactivity in bone.", "mechanism": "Chronic IGF-1 excess disrupts bone remodeling, contributing to osteoporosis.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "medium", "disease": "Acromegalic heart disease (AHD)", "glycan_involvement": "Glycosylation influences IGF-1 stability and tissue targeting.", "mechanism": "IGF-1 excess promotes cardiac hypertrophy and dysfunction.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12597749" }, { "confidence": "high", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD5 is a glycoprotein; glycosylation may affect its cell surface expression and signaling.", "mechanism": "Elevated CD5 levels increase risk by enhancing T-cell activation and inflammatory cytokine production.", "protein": "CD5", "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "high", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "OPG is a glycoprotein; glycosylation influences secretion and receptor binding.", "mechanism": "Elevated OPG promotes vascular inflammation and endothelial cell survival, increasing disease risk.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "high", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "Aberrant O-glycosylation of IgA1 promotes immune complex formation and pathogenicity.", "mechanism": "IgA deposition in vessel walls triggers neutrophil activation and vascular inflammation.", "protein": "IgA", "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD45 is highly glycosylated; glycosylation regulates isoform expression and signaling.", "mechanism": "CD45 expression on T cells modulates osteoprotegerin levels, influencing disease risk.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD38 glycosylation affects cell surface localization and function.", "mechanism": "CD38 marks activated B cells; its expression correlates with disease activity.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD25 glycosylation modulates receptor stability and signaling.", "mechanism": "CD25 on naive B cells increases IgAV risk, possibly via altered immune regulation.", "protein": "CD25 (IL2RA)", "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD39 glycosylation affects enzymatic activity and immune regulation.", "mechanism": "CD39+ Tregs influence threonate levels, modulating inflammation and disease risk.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "HLA DR glycosylation is critical for peptide binding and immune recognition.", "mechanism": "HLA DR on monocytes modulates CD5 and chiro-inositol, impacting antigen presentation and inflammation.", "protein": "HLA DR", "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD127 glycosylation affects receptor function and signaling.", "mechanism": "High CD127 on CD4+ T cells promotes inflammatory processes in IgAV.", "protein": "CD127 (IL7R)", "protein_enriched": { "function": "Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP)", "gene_name": "IL7R", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P16871" }, "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "medium", "disease": "IgA vasculitis (Henoch-Schonlein purpura)", "glycan_involvement": "CD28 glycosylation regulates ligand binding and T cell activation.", "mechanism": "CD28+ CD45RA- CD8dim T cells modulate metabolite levels, influencing disease risk.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC12597849" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Citrullination may occur on glycoproteins, altering glycan structures and antigenicity.", "mechanism": "Citrullinated peptides act as neoantigens, triggering autoantibody (ACPA) production and autoimmunity in RA.", "protein": "Citrullinated peptides", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12598268" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Non-enzymatic glycation modifies glycoproteins, increasing immunogenicity.", "mechanism": "AGEs formed by smoking-induced glycation act as autoantigens, enhancing autoimmunity.", "protein": "Advanced glycation end products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "N-glycosylation changes on Fc region modulate immune function.", "mechanism": "Altered glycosylation of IgG (e.g., increased agalactosylation) is associated with RA activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12598268" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycation of LDL increases its atherogenicity.", "mechanism": "Smoking-derived AGEs accumulate on LDL, promoting atherogenesis.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Citrullination of glycoproteins in oral mucosa increases antigenicity.", "mechanism": "Bacterial PADI citrullinates host peptides in oral cavity, triggering RA autoimmunity.", "protein": "Porphyromonas gingivalis PADI enzyme", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "NETs contain glycoproteins; altered glycosylation may enhance immunogenicity.", "mechanism": "NETs expose modified self-antigens, promoting autoantibody production.", "protein": "Neutrophil extracellular traps (NETs)", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation of flagellin affects immune recognition.", "mechanism": "Bacterial flagellin from dysbiotic gut microbiota triggers immune activation in RA.", "protein": "Flagellin", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "LPS is a glycolipid/glycoprotein; glycan moiety is essential for immune activation.", "mechanism": "LPS from gut bacteria activates TLRs, promoting inflammation.", "protein": "Lipopolysaccharides (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Fas is N-glycosylated; glycosylation may affect receptor function.", "mechanism": "Smoking increases Fas expression, enhancing apoptosis and exposure of autoantigens.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "PADI may be glycosylated, affecting its activity and localization.", "mechanism": "Smoking upregulates PADI in lung/immune cells, increasing citrullinated autoantigens.", "protein": "Peptidyl arginine deiminase (PADI)", "protein_enriched": { "function": "Catalyzes the deimination of arginine residues of proteins", "gene_name": "PADI1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9ULC6" }, "relationship_type": "causal", "source_pmcid": "PMC12598268" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Altered N-glycosylation (high-mannose) on sEV surface proteins.", "mechanism": "Increased density and accessibility of high-mannose glycans on sEVs from metastatic melanoma cells detected by Con A binding.", "protein": "High-mannose glycan motifs (Con A ligands)", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect detection efficiency; altered in metastatic cells.", "mechanism": "CD81 is enriched in sEVs from melanoma cells and used as an exosome marker.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may mask antibody epitopes in metastatic sEVs.", "mechanism": "CD63 is a standard exosome marker present in melanoma-derived sEVs.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Potential glycosylation changes in metastatic sEVs.", "mechanism": "Flotillin-1 is used to confirm exosomal identity of sEVs from melanoma cells.", "protein": "Flotillin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles", "gene_name": "FLOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O75955" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Not specified.", "mechanism": "Tsg101 is a marker for exosome cargo in melanoma sEVs.", "protein": "Tsg101", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Altered O-glycosylation patterns.", "mechanism": "Aberrantly glycosylated MUC1 on EVs discriminates breast cancer cells.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Increased sialylation of N-glycans.", "mechanism": "Sialylated N-glycans on EVs serve as diagnostic markers in various cancers.", "protein": "Sialylated N-glycans", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Altered fucosylation.", "mechanism": "UEA I-binding fucosylated glycans on exosomes discriminate CRC subtypes and progression.", "protein": "L-fucosylated glycan motifs (UEA I ligands)", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "medium", "disease": "Drug resistance in melanoma", "glycan_involvement": "Dynamic changes in high-mannose N-glycans.", "mechanism": "Altered glycan signatures on sEVs reflect phenotype switching and therapy resistance.", "protein": "High-mannose glycan motifs (Con A ligands)", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Stage-specific N-glycosylation changes.", "mechanism": "Surface high-mannose glycans on sEVs distinguish primary from metastatic melanoma.", "protein": "High-mannose glycan motifs (Con A ligands)", "relationship_type": "biomarker", "source_pmcid": "PMC12599222" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "O-glycosylation of dystrophin is important for membrane association and stability.", "mechanism": "Loss of dystrophin due to gene deletion leads to muscle fiber instability and progressive muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "high", "disease": "Glycerol kinase deficiency", "glycan_involvement": "Glycosylation may affect enzyme stability and localization.", "mechanism": "Deletion of GK gene impairs glycerol phosphorylation, causing accumulation of free glycerol and pseudo-hypertriglyceridemia.", "protein": "Glycerol kinase", "protein_enriched": { "function": "Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. Sn-glycerol 3-phosphate is a crucial intermediate in various metabolic pathways,", "gene_name": "GK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P32189" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "high", "disease": "X-linked adrenal hypoplasia congenita", "glycan_involvement": "Potential nuclear glycosylation may regulate protein function.", "mechanism": "NR0B1 deletion disrupts adrenal development, leading to primary adrenal insufficiency.", "protein": "NR0B1 (DAX1)", "protein_enriched": { "function": "Receptor for WNT2 that is coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-cateni", "gene_name": "FZD9", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G41247ZX", "G47644PP", "G62765YT" ], "uniprot_id": "O00144" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may influence CK secretion and stability.", "mechanism": "Elevated CK in serum reflects muscle breakdown due to dystrophin deficiency.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599579" }, { "confidence": "high", "disease": "X-linked adrenal hypoplasia congenita", "glycan_involvement": "Glycosylation is essential for ACTH secretion and receptor binding.", "mechanism": "Elevated ACTH is a compensatory response to low cortisol in adrenal insufficiency.", "protein": "Adrenocorticotropic hormone (ACTH)", "protein_enriched": { "function": "Stimulates the adrenal glands to release cortisol", "gene_name": "POMC", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01189" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599579" }, { "confidence": "medium", "disease": "Adrenal crisis", "glycan_involvement": "N-glycosylation required for renin secretion.", "mechanism": "High plasma renin reflects compensatory response to mineralocorticoid deficiency.", "protein": "Renin", "relationship_type": "biomarker", "source_pmcid": "PMC12599579" }, { "confidence": "high", "disease": "Xp21 contiguous gene deletion syndrome", "glycan_involvement": "O-glycosylation affects dystrophin's membrane interactions.", "mechanism": "Dystrophin gene deletion is a component of the contiguous gene syndrome, contributing to neuromuscular symptoms.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "medium", "disease": "Pseudo-hypertriglyceridemia", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "GK deficiency leads to elevated free glycerol, mimicking hypertriglyceridemia.", "protein": "Glycerol kinase", "protein_enriched": { "function": "Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. Sn-glycerol 3-phosphate is a crucial intermediate in various metabolic pathways,", "gene_name": "GK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P32189" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "medium", "disease": "Xp21 contiguous gene deletion syndrome", "glycan_involvement": "Possible nuclear glycosylation modulates function.", "mechanism": "NR0B1 deletion contributes to adrenal insufficiency within the syndrome.", "protein": "NR0B1 (DAX1)", "protein_enriched": { "function": "Receptor for WNT2 that is coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-cateni", "gene_name": "FZD9", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G41247ZX", "G47644PP", "G62765YT" ], "uniprot_id": "O00144" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "low", "disease": "Sudden infant death", "glycan_involvement": "Loss of glycosylated dystrophin impairs muscle integrity.", "mechanism": "Severe neuromuscular involvement due to dystrophin loss may contribute to fatal outcomes.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12599579" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "MAG is heavily glycosylated; glycan epitopes may be targeted by autoantibodies.", "mechanism": "MAG antibodies are sometimes found in CIDP, indicating immune-mediated attack on myelin glycoproteins.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599595" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Gangliosides are glycosylated lipids; glycan moieties are immunogenic.", "mechanism": "Anti-GM1 antibodies are assayed in CIDP to rule out nodopathy; negative in this cohort.", "protein": "Ganglioside GM1", "relationship_type": "biomarker", "source_pmcid": "PMC12599595" }, { "confidence": "high", "disease": "Autoimmune nodopathies", "glycan_involvement": "Contactin-1 is N-glycosylated; glycan structures may influence antibody binding.", "mechanism": "Antibodies against paranodal glycoproteins define autoimmune nodopathies, distinct from CIDP.", "protein": "Paranodal glycoproteins (e.g., Contactin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12599595" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIg is effective in CIDP, likely by modulating pathogenic autoantibodies and immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12599595" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Albumin is glycosylated; glycan status not directly implicated in CIDP.", "mechanism": "Albuminocytological dissociation (high CSF protein, normal cell count) is a diagnostic feature of CIDP.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12599595" }, { "confidence": "high", "disease": "Intelligence (cognitive function)", "glycan_involvement": "GlycA is a composite N-acetyl signal from multiple acute-phase glycoproteins; reflects glycosylation changes during inflammation.", "mechanism": "Higher circulating GlycA levels are causally associated with reduced intelligence; likely mediated by chronic inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "causal", "source_pmcid": "PMC12599776" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Reflects increased N-acetylation of glycoproteins during inflammation.", "mechanism": "Elevated GlycA predicts long-term cardiovascular risk.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation changes in acute-phase proteins.", "mechanism": "High GlycA levels predict future diabetes risk.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "medium", "disease": "Certain cancers", "glycan_involvement": "Reflects systemic inflammation via glycosylated proteins.", "mechanism": "Elevated GlycA associated with increased cancer risk.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "medium", "disease": "Severe infections", "glycan_involvement": "Acute-phase glycoprotein glycosylation changes.", "mechanism": "High GlycA predicts risk of severe infections.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-acetyl signals from glycosylated acute-phase proteins.", "mechanism": "GlycA is a marker of chronic systemic inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "medium", "disease": "Intelligence (cognitive function)", "glycan_involvement": "ApoE is N-glycosylated, which affects its receptor binding and lipid transport.", "mechanism": "ApoE in VLDL binds to VLDL/LDL receptors, influencing lipid metabolism and potentially cognitive function.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "mechanistic/biomarker", "source_pmcid": "PMC12599776" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Low serum albumin reflects malnutrition and inflammation, predicting higher mortality in HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "high", "disease": "All-cause mortality", "glycan_involvement": "Altered glycosylation may affect albumin clearance and function.", "mechanism": "Hypoalbuminemia is associated with increased risk of death from all causes in HF patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "high", "disease": "Cardiovascular mortality", "glycan_involvement": "Glycosylation status may modulate albumin's anti-inflammatory properties.", "mechanism": "Low albumin predicts higher cardiovascular death risk in HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Hemoglobin glycation (not classic glycosylation) is a marker of metabolic status.", "mechanism": "Included in HALP score; low hemoglobin reflects anemia and poor prognosis.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Neutrophil surface glycoproteins mediate migration and activation.", "mechanism": "Neutrophil-to-lymphocyte ratio (NLR) is part of ALI; high NLR reflects inflammation and predicts mortality.", "protein": "Neutrophil markers", "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Lymphocyte glycoproteins regulate immune response.", "mechanism": "Low lymphocyte count (in NLR, HALP) reflects immune suppression and worse prognosis.", "protein": "Lymphocyte markers", "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Erythrocyte membrane glycoproteins affect cell deformability and survival.", "mechanism": "High RDW (in RAR) reflects erythrocyte heterogeneity, inflammation, and predicts short-term mortality.", "protein": "Red cell distribution width (RDW) proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "Glycosylation may affect albumin's nutritional biomarker reliability.", "mechanism": "Low albumin is a marker of poor nutritional status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Inflammation can alter glycosylation patterns.", "mechanism": "Albumin decreases during inflammation; used in composite indices (ALI, RAR, etc.).", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Platelet glycoproteins mediate aggregation and vascular interactions.", "mechanism": "Platelet count (in HALP) reflects hemostatic and inflammatory status; low counts predict worse outcomes.", "protein": "Platelet markers", "relationship_type": "biomarker", "source_pmcid": "PMC12602239" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Terminal galactoside moiety mediates TLR4 interaction.", "mechanism": "Inhibits insulin receptor signaling, promotes inflammation via TLR4, predicts T2DM onset.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12602975" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation required for TLR4 binding.", "mechanism": "Blocks insulin receptor autophosphorylation, impairs IRS-1 signaling, enhances FFA-TLR4 inflammation.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "causal", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation status may reflect liver damage.", "mechanism": "Elevated fetuin-A predicts NAFLD; activates NF-\u03baB, inhibits IRS function.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Not specified.", "mechanism": "High fetuin-A linked to increased CVD risk via insulin resistance and pro-atherogenic effects.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12602975" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Urinary post-translationally modified fetuin-A fragments (uPTM-FetA) are sensitive markers.", "mechanism": "Urinary and serum fetuin-A levels correlate with nephropathy progression; lower levels linked to advanced disease.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "Not specified.", "mechanism": "Elevated serum/vitreous fetuin-A associated with presence and progression of retinopathy.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker", "source_pmcid": "PMC12602975" }, { "confidence": "low", "disease": "Diabetic Neuropathy", "glycan_involvement": "Not specified.", "mechanism": "Lower fetuin-A levels associated with higher neuropathy incidence; correlation with neuropathy severity.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not specified.", "mechanism": "Elevated fetuin-A in obesity; knockout mice resistant to diet-induced obesity.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "Lower fetuin-A linked to increased atherosclerosis and vascular calcification; high levels may be pro-atherogenic.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12602975" }, { "confidence": "medium", "disease": "Vascular Calcification", "glycan_involvement": "Not specified.", "mechanism": "Lower fetuin-A facilitates vascular calcification; may act as a calcification inhibitor.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein, AHSG)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12602975" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation patterns of acute phase proteins modulate their inflammatory properties and stability.", "mechanism": "Circulating glycoprotein acetyls reflect integrated concentration and glycosylation of acute phase proteins released during inflammation, correlating with disease activity and mortality risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12603704" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Altered glycosylation during acute phase response enhances pro-inflammatory signaling.", "mechanism": "Elevated glycoprotein acetyls indicate increased inflammation and higher mortality risk in UC patients.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12603704" }, { "confidence": "medium", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation changes in acute phase proteins contribute to immune dysregulation.", "mechanism": "Higher levels of glycoprotein acetyls are associated with increased inflammation and mortality risk in CD.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12603704" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Lifestyle may modulate glycosylation of acute phase proteins, reducing inflammatory burden.", "mechanism": "Decreased glycoprotein acetyls mediate part of the beneficial effect of healthy lifestyle on reduced mortality in IBD.", "protein": "Glycoprotein acetyls", "relationship_type": "causal", "source_pmcid": "PMC12603704" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "N-glycosylation at specific ACE2 sites modulates viral binding and host specificity.", "mechanism": "ACE2 serves as the entry receptor for several bat merbecoviruses, enabling cross-species transmission.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Absence of N-glycan at position 329 permits viral binding.", "mechanism": "HKU5 spike binds specifically to P. abramus ACE2, enabling infection.", "protein": "Bat ACE2 (Pipistrellus abramus)", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Presence of N-glycan at 329 sterically hinders viral attachment.", "mechanism": "N-glycosylation at position 329 blocks HKU5 spike binding, preventing infection.", "protein": "Bat ACE2 (Pipistrellus pipistrellus)", "relationship_type": "protective", "source_pmcid": "PMC12604803" }, { "confidence": "medium", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Glycosylation patterns influence binding specificity.", "mechanism": "BtVs-SC2013 and P. khulii-2011 spikes bind to Murina aurata ACE2, enabling infection.", "protein": "Bat ACE2 (Murina aurata)", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Key ACE2 residues and glycosylation modulate susceptibility.", "mechanism": "BtVs-SC2013 and HKU25 spikes bind mink ACE2, suggesting mink as potential intermediate hosts.", "protein": "Mink ACE2", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "medium", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Glycosylation may affect binding but not explicitly detailed.", "mechanism": "HKU25 spike binds pangolin ACE2, indicating pangolins as possible intermediate hosts.", "protein": "Pangolin ACE2", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Spike glycosylation not directly discussed, but host ACE2 glycosylation is key.", "mechanism": "HKU5 is closely related to MERS-CoV; spike protein mediates host entry via ACE2 or DPP4.", "protein": "Coronavirus Spike (HKU5)", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "medium", "disease": "Potential future coronavirus pandemics", "glycan_involvement": "Glycan barriers at ACE2 sites modulate cross-species risk.", "mechanism": "Species-specific ACE2 usage by bat viruses highlights risk of adaptation to humans.", "protein": "Bat ACE2 (Pipistrellus abramus)", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "N-glycan at 329 blocks viral attachment.", "mechanism": "N-glycosylation at position 329 prevents HKU5 binding.", "protein": "Bat ACE2 (Pipistrellus kuhlii)", "relationship_type": "protective", "source_pmcid": "PMC12604803" }, { "confidence": "high", "disease": "Coronavirus zoonotic spillover", "glycan_involvement": "Host ACE2 glycosylation modulates susceptibility.", "mechanism": "Spike proteins bind ACE2 from multiple species, facilitating host jumps.", "protein": "Coronavirus Spike (BtVs-SC2013, HKU25)", "relationship_type": "causal", "source_pmcid": "PMC12604803" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Defective removal of N-linked glycans from misfolded glycoproteins impairs their degradation.", "mechanism": "Heterozygous NGLY1 variant impairs deglycosylation of misfolded glycoproteins, leading to proteostasis disruption, ER stress, and neuroinflammation, which may modify PD phenotype.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "causal/modifier", "source_pmcid": "PMC12604884" }, { "confidence": "high", "disease": "Congenital disorder of deglycosylation (NGLY1 deficiency)", "glycan_involvement": "Failure to remove N-linked glycans from glycoproteins.", "mechanism": "Biallelic loss-of-function mutations in NGLY1 cause impaired deglycosylation and accumulation of misfolded glycoproteins.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "causal", "source_pmcid": "PMC12604884" }, { "confidence": "low", "disease": "Autoimmune polyendocrine syndrome type III (APS-3)", "glycan_involvement": "Altered glycoprotein processing may affect immune signaling.", "mechanism": "NGLY1 variant may contribute to immune dysregulation via impaired protein clearance and increased cellular stress.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "modifier", "source_pmcid": "PMC12604884" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Persistence of N-linked glycans on misfolded proteins prevents their degradation.", "mechanism": "Accumulation of misfolded glycoproteins due to impaired ERAD and deglycosylation contributes to neuronal stress and degeneration.", "protein": "Misfolded glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12604884" }, { "confidence": "low", "disease": "Seronegative arthritis", "glycan_involvement": "Altered glycoprotein clearance may affect immune cell signaling.", "mechanism": "Impaired deglycosylation may promote innate immune activation and inflammation.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "modifier", "source_pmcid": "PMC12604884" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Indirect; impaired deglycosylation leads to inflammatory signaling.", "mechanism": "JAK inhibition (tofacitinib) may counteract neuroinflammation triggered by NGLY1-related proteostasis disruption.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12604884" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Reflects altered glycoprotein processing capacity.", "mechanism": "Heterozygous NGLY1 variant may serve as a genetic biomarker for susceptibility to neuroimmune-modified PD.", "protein": "N-glycanase 1 (NGLY1)", "protein_enriched": { "function": "Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glyca", "gene_name": "NGLY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96IV0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12604884" }, { "confidence": "high", "disease": "Classical swine fever", "glycan_involvement": "Glycosylation of E2 is important for immunogenicity and antigenicity.", "mechanism": "E2 glycoprotein used as antigen in mRNA-LNP vaccine induces strong neutralizing antibody and T-cell responses, conferring protection.", "protein": "CSFV E2 glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA glycosylation modulates antigenicity and immune recognition.", "mechanism": "HA DNA delivered via nanoparticles elicits robust and durable T-cell and antibody responses, providing cross-strain protection.", "protein": "Influenza hemagglutinin (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation critical for proper folding and immunogenicity.", "mechanism": "Soluble glycoprotein immunization elicits cross-reactive antibodies and full protection in animal model.", "protein": "Nipah virus glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Hendra virus infection", "glycan_involvement": "Glycosylation required for antigenicity and vaccine efficacy.", "mechanism": "Soluble glycoprotein immunization provides cross-protection against Nipah virus.", "protein": "Hendra virus glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Bovine viral diarrhea", "glycan_involvement": "Glycosylation affects epitope recognition by antibodies.", "mechanism": "E2 glycoprotein is target for monoclonal antibody-based cELISA for diagnosis and surveillance.", "protein": "BVDV E2 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Transmissible gastroenteritis", "glycan_involvement": "Glycosylation influences antigenicity and assay specificity.", "mechanism": "Spike glycoprotein used in pseudovirus neutralization assay for serological diagnosis.", "protein": "TGEV spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12605159" }, { "confidence": "medium", "disease": "Feline herpesvirus infection", "glycan_involvement": "Glycosylation required for viral entry and immunogenicity.", "mechanism": "FHV-1 vector expressing heterologous antigens induces protective immunity.", "protein": "FHV-1 glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "medium", "disease": "Feline calicivirus infection", "glycan_involvement": "Potential glycosylation may affect immunogenicity.", "mechanism": "VP1-based VLP vaccine induces neutralizing antibodies and full protection.", "protein": "FCV VP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "medium", "disease": "Feline panleukopenia", "glycan_involvement": "Possible glycosylation may influence antigenicity.", "mechanism": "FPV VP2 expressed in FHV-1 vector induces protective immunity.", "protein": "FPV VP2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "medium", "disease": "Fowl cholera", "glycan_involvement": "Bacterial glycoproteins contribute to immunogenicity.", "mechanism": "Gamma-irradiated bacteria with preserved glycoproteins induce strong humoral and cellular immunity.", "protein": "Pasteurella multocida outer membrane proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605159" }, { "confidence": "high", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity", "mechanism": "gB mediates viral entry into host cells and elicits neutralizing antibodies", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation modulates antigenicity and host interaction", "mechanism": "gC facilitates viral attachment and entry; induces neutralizing antibodies", "protein": "gC", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation enhances immunogenicity and vaccine efficacy", "mechanism": "gD is essential for viral entry and a major target for neutralizing antibodies", "protein": "gD", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation affects immune recognition and vaccine differentiation", "mechanism": "gE is involved in immune evasion and virulence; deletion attenuates pathogenicity", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "medium", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation modulates immune response", "mechanism": "gG contributes to virulence; deletion reduces pathogenicity", "protein": "gG", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "medium", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement", "mechanism": "TK is associated with virulence; deletion attenuates disease", "protein": "TK", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "medium", "disease": "Reproductive disorders (abortion)", "glycan_involvement": "Glycosylation influences tissue tropism", "mechanism": "gE contributes to virulence in reproductive tissues; deletion reduces abortion risk", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "medium", "disease": "Immunosuppression in cattle", "glycan_involvement": "Glycosylation masks epitopes from immune detection", "mechanism": "gE mediates immune evasion, leading to immunosuppression", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Bovine respiratory disease complex", "glycan_involvement": "Glycosylation required for antigenicity in ELISA", "mechanism": "gB is a major antigen detected in diagnostic assays for BoHV-1", "protein": "gB", "relationship_type": "biomarker", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Infectious bovine rhinotracheitis (IBR)", "glycan_involvement": "Glycosylation status used in diagnostic differentiation", "mechanism": "gE deletion used in vaccine design to differentiate infected from vaccinated animals", "protein": "gE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605209" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Galactoarabinan glycan moiety mediates recognition by TLR4, triggering immunomodulatory effects.", "mechanism": "LBNP-1 reverses tumor-associated macrophage (TAM) phenotype from immunosuppressive M2 to antitumor M1 via TLR4/NF-\u03baB signaling, leading to inhibition of colorectal cancer cell proliferation.", "protein": "LBNP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycoprotein structure enables interaction with macrophage receptors, driving phenotype shift.", "mechanism": "Conditioned medium from LBNP-1-treated M2 macrophages inhibits colorectal cancer cell growth, indicating indirect antitumor activity.", "protein": "LBNP-1", "relationship_type": "protective", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Branched arabinan glycan structure is essential for receptor binding and downstream signaling.", "mechanism": "LBNP-1 activates NF-\u03baB signaling in macrophages, promoting M1 polarization and antitumor cytokine production.", "protein": "LBNP-1", "relationship_type": "causal", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycan moiety is recognized by TLR4, initiating immune response.", "mechanism": "LBNP-1\u2019s effect is blocked by TLR4 antagonist, confirming TLR4-mediated immunomodulation as a therapeutic mechanism.", "protein": "LBNP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation pattern facilitates selective receptor engagement and immune activation.", "mechanism": "LBNP-1 decreases M2 macrophage markers (Arg-1, CD206) and increases M1 markers (iNOS, TNF-\u03b1, IL-6, IL-1\u03b2), shifting macrophage phenotype toward tumor suppression.", "protein": "LBNP-1", "relationship_type": "protective", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycoprotein\u2019s carbohydrate portion is critical for immune cell interaction.", "mechanism": "LBNP-1 does not directly kill cancer cells but modulates the tumor microenvironment via macrophage polarization.", "protein": "LBNP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605246" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Presence of galactoarabinan glycan is necessary for biomarker activity.", "mechanism": "LBNP-1-induced macrophage phenotype shift can serve as a biomarker for immunomodulatory response in CRC.", "protein": "LBNP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12605246" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycan structure allows partial recognition by TLR2.", "mechanism": "LBNP-1\u2019s immunomodulatory effect is partially mediated by TLR2, though TLR4 is dominant.", "protein": "LBNP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycoprotein\u2019s glycan moiety is essential for immune modulation.", "mechanism": "LBNP-1 alleviates immunosuppressive tumor microenvironment, enhancing antitumor immunity.", "protein": "LBNP-1", "relationship_type": "protective", "source_pmcid": "PMC12605246" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycoprotein nature (protein + glycan) is required for full activity.", "mechanism": "LBNP-1\u2019s amino acid composition may contribute to its immunomodulatory and antitumor properties.", "protein": "LBNP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12605246" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for stability and function.", "mechanism": "Promotes M1 macrophage activation, increases inflammatory cytokines, exacerbates intestinal inflammation and tissue injury.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "causal", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Glycosylation enables secretion and immune modulation.", "mechanism": "Neutralizing AHSG with antibody reduces inflammation and tissue damage in NEC mouse model.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12606173" }, { "confidence": "medium", "disease": "Inflammatory bowel diseases", "glycan_involvement": "Glycosylation mediates immune interactions.", "mechanism": "Drives M1 macrophage polarization and pro-inflammatory cytokine production.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "causal", "source_pmcid": "PMC12606173" }, { "confidence": "medium", "disease": "Autoimmune encephalomyelitis", "glycan_involvement": "Glycosylation required for immune function.", "mechanism": "Deficiency protects against disease by dampening innate immunity.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "causal", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Indirect; regulates glycoprotein AHSG expression.", "mechanism": "Upregulates AHSG via methionine/SAM pathway, promoting M1 macrophage activation and inflammation.", "protein": "Betaine\u2013homocysteine S-methyltransferase 2 (BHMT2)", "protein_enriched": { "function": "Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) ", "gene_name": "NCOA5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HCD5" }, "relationship_type": "causal", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Indirect; regulates glycoprotein AHSG expression.", "mechanism": "Upregulates AHSG via SAM-mediated histone methylation, promoting M1 macrophage activation.", "protein": "Methionine adenosyltransferase 1A (MAT1A)", "relationship_type": "causal", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Indirect; impacts glycoprotein AHSG.", "mechanism": "Silencing BHMT2 reduces AHSG, M1 macrophage activation, and tissue damage.", "protein": "Betaine\u2013homocysteine S-methyltransferase 2 (BHMT2)", "protein_enriched": { "function": "Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) ", "gene_name": "NCOA5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HCD5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Indirect; impacts glycoprotein AHSG.", "mechanism": "Silencing MAT1A reduces AHSG, M1 macrophage activation, and tissue damage.", "protein": "Methionine adenosyltransferase 1A (MAT1A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Glycosylation required for detection and function.", "mechanism": "Elevated AHSG levels in NEC tissue and plasma indicate disease presence and severity.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Glycosylation essential for secretion and immune modulation.", "mechanism": "Secreted by epithelial cells, acts on macrophages to drive inflammation.", "protein": "Alpha-2-HS-glycoprotein (AHSG, fetuin-A)", "relationship_type": "paracrine mediator", "source_pmcid": "PMC12606173" }, { "confidence": "high", "disease": "Gallbladder cancer", "glycan_involvement": "O-glycosylation of MUC16 is altered, contributing to immune evasion and cell adhesion.", "mechanism": "Significantly overexpressed in tumour tissue; associated with tumour progression, immune evasion, and metastasis.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "O-glycosylation affects mucin structure and tumour microenvironment.", "mechanism": "Elevated expression in tumours; may promote aggressive phenotype and mucinous carcinoma features.", "protein": "MUC19", "relationship_type": "biomarker", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Initiates O-glycosylation; defects lead to abnormal glycan structures on mucins.", "mechanism": "Defective GALNT12 pathway upregulated in tumours; implicated in aberrant O-glycosylation and oncogenesis.", "protein": "GALNT12", "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Initiates O-glycosylation; defects disrupt mucin glycosylation.", "mechanism": "Defective GALNT3 pathway upregulated in tumours; associated with altered glycosylation and tumour progression.", "protein": "GALNT3", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:16638743, ", "gene_name": "GALNT3", "glycan_count": 7, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G23719VF", "G24084IV", "G62765YT", "G75983OB", "G83229XP", "G95177YH" ], "uniprot_id": "Q14435" }, "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Chaperones core 1 O-glycan synthesis; defects lead to truncated O-glycans.", "mechanism": "Defective C1GALT1C1 pathway upregulated; affects core 1 O-glycan biosynthesis, impacting tumour biology.", "protein": "C1GALT1C1", "protein_enriched": { "function": "Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance. Associates with the striatin-interacting ", "gene_name": "CTTNBP2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8WZ74" }, "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "high", "disease": "Gallstone disease", "glycan_involvement": "O-glycosylation status differs between benign and malignant tissue.", "mechanism": "Lower expression in gallstone controls compared to tumours; supports use in distinguishing malignant vs. benign disease.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "differential expression", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Colorectal cancer susceptibility 1 (CRCS1)", "glycan_involvement": "Aberrant O-glycosylation of MUC16 due to GALNT12 defect.", "mechanism": "Defective GALNT12 pathway (affecting MUC16 glycosylation) linked to hereditary colorectal cancer susceptibility.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Hyperphosphatemic familial tumoural calcinosis (HFTC)", "glycan_involvement": "Altered O-glycosylation of MUC16 due to GALNT3 defect.", "mechanism": "Defective GALNT3 pathway (affecting MUC16 glycosylation) associated with HFTC.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Tn polyagglutination syndrome (TNPS)", "glycan_involvement": "Truncated O-glycans on MUC16 due to C1GALT1C1 defect.", "mechanism": "Defective C1GALT1C1 pathway (affecting MUC16 glycosylation) linked to TNPS.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "causal", "source_pmcid": "PMC12606196" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Aberrant O-glycosylation modulates immune recognition and cell adhesion.", "mechanism": "Potential target for therapy due to its role in immune evasion and tumour progression.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12606196" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered N-glycosylation patterns detected by MALDI-MSI", "mechanism": "N-glycan signatures associate with tumor grade and recurrence", "protein": "N-linked glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation changes in serum proteins", "mechanism": "Serum N-glycan profiles differentiate cancer from controls", "protein": "Glycan biomarkers", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Potential glycosylation affects fragment detection", "mechanism": "Tissue-localized MEKK2 fragment differentiates cancer from non-cancer tissue", "protein": "MEKK2 fragment", "protein_enriched": { "function": "Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6", "gene_name": "MAP3K4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycolipid composition altered in cancer tissue", "mechanism": "Phosphatidylcholine species differentiate tumor types", "protein": "Phosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "high", "disease": "Liver cancer/metastasis", "glycan_involvement": "Glycolipid metabolism altered in metastasis", "mechanism": "Elevated sphingomyelin species found in metastatic lesions", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycolipid signaling involved in metastatic potential", "mechanism": "Specific PI compositions correlate with invasion and nodal metastasis", "protein": "Phosphoinositides", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation status affects histone detection", "mechanism": "SELDI surface chemistry captures histone glycoproteins for cancer detection", "protein": "Histones", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate energy metabolism", "mechanism": "Higher adenylate energy charge in tumors than non-tumors", "protein": "ATP/ADP/AMP", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Pheochromocytoma/paraganglioma (PPGL)", "glycan_involvement": "Glycosylation may modulate enzyme activity", "mechanism": "Kynurenine pathway metabolite alterations associate with metastatic behavior", "protein": "Kynurenine pathway enzymes", "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation impacts protein stability and detection", "mechanism": "Detected as a high-mass glycoprotein in cancer tissue", "protein": "Carboxypeptidase A", "protein_enriched": { "function": "Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro (PubMed:20385563, PubMed:8806703). Catalyzes the conversion of l", "gene_name": "CPA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15085" }, "relationship_type": "biomarker", "source_pmcid": "PMC12606767" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation required for secretion and immune recognition.", "mechanism": "HBsAg positivity used to define HBV infection status in NPC patients; not directly associated with increased liver metastasis risk.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma (NPC)", "glycan_involvement": "Glycosylation affects antigenicity and detection.", "mechanism": "HBsAg used to stratify NPC patients by HBV infection status.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "HBeAg is glycosylated; glycosylation affects secretion and immune modulation.", "mechanism": "HBeAg positivity associated with high HBV replication, which correlates with increased liver metastasis risk in NPC.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "high", "disease": "Chronic Hepatitis B infection", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "HBsAg positivity defines chronic HBV infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "high", "disease": "Chronic Hepatitis B infection", "glycan_involvement": "Glycosylation modulates immune tolerance.", "mechanism": "HBeAg positivity indicates active viral replication.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences immune evasion and chronicity.", "mechanism": "Chronic HBsAg positivity is a risk factor for HCC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12607084" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects immune response.", "mechanism": "HBeAg positivity reflects high viral load, associated with HCC risk.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12607084" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Glycosylation maintains antigen stability and immune interactions.", "mechanism": "Low HBV-DNA (often HBsAg positive, low replication) associated with reduced liver metastasis in NPC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "protective", "source_pmcid": "PMC12607084" }, { "confidence": "high", "disease": "Liver metastasis", "glycan_involvement": "Glycosylation may modulate immune evasion and persistence.", "mechanism": "High HBV-DNA (often HBsAg positive, high replication) increases risk of liver metastasis in NPC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12607084" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Glycosylation may affect immune modulation.", "mechanism": "HBeAg positivity (marker of high viral replication) correlates with increased liver metastasis risk in NPC.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "causal", "source_pmcid": "PMC12607084" }, { "confidence": "high", "disease": "VEXAS syndrome", "glycan_involvement": "Indirect; UBA1 is not classically glycosylated but regulates protein turnover including glycoproteins.", "mechanism": "Somatic mutations in UBA1 disrupt ubiquitylation, leading to autoinflammation and myelodysplasia.", "protein": "UBA1 (Ubiquitin-like modifier activating enzyme 1)", "protein_enriched": { "function": "Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquit", "gene_name": "UBA1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G31370VX" ], "uniprot_id": "P22314" }, "relationship_type": "causal", "source_pmcid": "PMC12607736" }, { "confidence": "high", "disease": "VEXAS syndrome", "glycan_involvement": "IL-6 is N-glycosylated, affecting secretion and receptor binding.", "mechanism": "IL-6 is a key inflammatory cytokine elevated in VEXAS; anti-IL-6 therapy (tocilizumab) reduces symptoms.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "VEXAS syndrome", "glycan_involvement": "IL-8 glycosylation modulates activity and stability.", "mechanism": "IL-8 is upregulated in VEXAS, contributing to neutrophil recruitment and inflammation.", "protein": "Interleukin-8 (IL-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "VEXAS syndrome", "glycan_involvement": "TNF-\u03b1 glycosylation affects receptor interaction.", "mechanism": "TNF-\u03b1 is elevated in VEXAS, driving inflammation; anti-TNF agents have limited efficacy.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "VEXAS syndrome", "glycan_involvement": "IFN-\u03b3 glycosylation influences immune signaling.", "mechanism": "IFN-\u03b3 is part of the inflammatory cascade in VEXAS.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "\u03b22GPI is heavily glycosylated, modulating its immunogenicity.", "mechanism": "\u03b22GPI antibodies are tested in VEXAS patients with thrombosis; usually negative, but relevant for differential diagnosis.", "protein": "Beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "Immunoglobulin A (IgA) vasculitis", "glycan_involvement": "O-glycosylation in IgA hinge region modulates pathogenicity.", "mechanism": "IgA vasculitis reported in VEXAS; IgA glycosylation affects immune complex formation.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12607736" }, { "confidence": "low", "disease": "Macrocytic anemia", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Deficiency can cause vacuolization in bone marrow, differential for VEXAS.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation critical for secretion and activity.", "mechanism": "Elevated Factor VIII levels observed in VEXAS patients with thrombosis.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation required for coagulation function.", "mechanism": "Elevated Factor IX levels observed in VEXAS patients with thrombosis.", "protein": "Factor IX", "relationship_type": "biomarker", "source_pmcid": "PMC12607736" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Gc is a glycoprotein; glycosylation is essential for folding and function.", "mechanism": "Gc mediates viral membrane fusion and entry; inhibition blocks infection.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 syndrome (secondary to OROV)", "glycan_involvement": "Gc glycosylation may influence neurotropism.", "mechanism": "OROV infection via Gc-mediated entry can trigger neurological complications.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12607964" }, { "confidence": "medium", "disease": "Stillbirth (vertical transmission of OROV)", "glycan_involvement": "Glycosylation may affect placental crossing.", "mechanism": "OROV entry via Gc glycoprotein implicated in vertical transmission and fetal infection.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Ligand binding may alter glycoprotein conformation.", "mechanism": "Curcumin binds and stabilizes Gc in prefusion state, inhibiting viral entry.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Binding may affect glycosylated regions.", "mechanism": "Berberine binds Gc, stabilizing prefusion conformation and blocking fusion.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Interaction with glycosylated domains possible.", "mechanism": "Quercetin binds Gc, inhibits viral entry (validated positive control).", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "medium", "disease": "Oropouche virus infection", "glycan_involvement": "Likely interact with glycosylated regions.", "mechanism": "Baicalin, naringin, cynaroside, lonicerin bind Gc, stabilize structure, may inhibit entry.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "Gc head domain is target of neutralizing antibodies; immunogenic marker.", "protein": "Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12607964" }, { "confidence": "medium", "disease": "Oropouche virus infection", "glycan_involvement": "Gn is glycosylated; glycosylation required for function.", "mechanism": "Gn assists Gc in viral attachment; potential target for entry inhibition.", "protein": "Gn glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Oropouche virus infection", "glycan_involvement": "Glycosylation required for proper folding and fusion activity.", "mechanism": "Gc glycoprotein structural rearrangement is essential for OROV entry and pathogenesis.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12607964" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Nrf2 is glycosylated, affecting stability and nuclear translocation.", "mechanism": "Nrf2 activation protects against oxidative stress and cardiac remodeling; EGCG enhances Nrf2 activity.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Keap1 glycosylation may affect its interaction with Nrf2.", "mechanism": "Keap1 regulates Nrf2 degradation; EGCG modifies Keap1 cysteines, stabilizing Nrf2.", "protein": "Keap1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "HO-1 glycosylation influences enzyme activity.", "mechanism": "HO-1 upregulated by Nrf2 activation, detoxifies ROS, protects myocardium.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "NQO1 glycosylation affects stability.", "mechanism": "NQO1 upregulated by Nrf2, reduces oxidative damage.", "protein": "NQO1", "protein_enriched": { "function": "Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons ar", "gene_name": "NQO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15559" }, "relationship_type": "protective", "source_pmcid": "PMC12607985" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "TGF-\u03b21 is heavily glycosylated, essential for secretion and receptor binding.", "mechanism": "TGF-\u03b21/Smad3 signaling drives cardiac fibrosis; EGCG inhibits this pathway.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Smad3 glycosylation modulates nuclear translocation.", "mechanism": "Smad3 mediates TGF-\u03b21-induced fibrosis; EGCG suppresses Smad3 activation.", "protein": "Smad3", "protein_enriched": { "function": "Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194).", "gene_name": "SMAD5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99717" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "NF-\u03baB glycosylation affects DNA binding and transcriptional activity.", "mechanism": "NF-\u03baB drives inflammatory cytokine production; EGCG inhibits NF-\u03baB activation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Mitochondrial Dysfunction", "glycan_involvement": "AMPK glycosylation influences activity and localization.", "mechanism": "AMPK regulates energy metabolism; EGCG activates AMPK, improving mitochondrial function.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Mitochondrial Dysfunction", "glycan_involvement": "PGC-1\u03b1 glycosylation affects coactivator function.", "mechanism": "PGC-1\u03b1 promotes mitochondrial biogenesis; EGCG enhances PGC-1\u03b1 activity.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12607985" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation critical for cell\u2013cell interaction and signaling.", "mechanism": "EndMT contributes to fibrosis; EGCG inhibits EndMT and fibrotic transformation.", "protein": "Endothelial cell adhesion molecules", "relationship_type": "causal", "source_pmcid": "PMC12607985" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "S-layer is glycosylated, affecting immune recognition and biofilm properties.", "mechanism": "Mediates immune evasion and biofilm formation by T. forsythia, promoting persistence in periodontal niche.", "protein": "S-layer", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Msp is modified with galactose-containing glycans, influencing coaggregation.", "mechanism": "Facilitates tissue invasion and immune modulation by T. denticola.", "protein": "Major Sheath Protein (Msp)", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Fimbriae interact with host glycoproteins and may be glycosylated.", "mechanism": "Mediates adhesion and invasion of host tissues by P. gingivalis.", "protein": "Fimbriae", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Adhesin domains interact with host glycoproteins; Hgp44 domain mediates coaggregation.", "mechanism": "Degrade host extracellular matrix and immune proteins, promoting tissue destruction.", "protein": "Gingipains (RgpA, Kgp)", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Surface-exposed, interacts with other glycoproteins; coaggregation partner.", "mechanism": "Mediates adhesion and triggers inflammation by T. forsythia.", "protein": "BspA", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "O-PS is a glycan structure essential for coaggregation.", "mechanism": "Mediates serotype-specific coaggregation between A. actinomycetemcomitans and F. nucleatum.", "protein": "O-polysaccharide (O-PS) of LPS", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Adhesin interacts with host glycoprotein E-cadherin.", "mechanism": "Binds E-cadherin, activates \u03b2-catenin signaling, promoting tumorigenesis.", "protein": "FadA", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Recognizes host glycans; mediates galactose-dependent coaggregation.", "mechanism": "Mediates adhesion and immune evasion, facilitating tumor colonization by F. nucleatum.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Surface-exposed, interacts with glycoprotein substrates.", "mechanism": "Degrades host proteins, facilitating tissue invasion by T. denticola.", "protein": "Dentilisin", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Leucine-rich repeat protein interacts with glycosylated BspA.", "mechanism": "Mediates coaggregation between T. denticola and T. forsythia, promoting pathogenic biofilm.", "protein": "LrrA", "relationship_type": "causal", "source_pmcid": "PMC12608652" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Altered N-glycosylation (decreased sialylation, increased fucosylation) reflects pro-inflammatory state.", "mechanism": "Obesity is associated with reduced sialylation and increased core fucosylation of IgG N-glycans.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Distinct N-glycan peaks differentiate GDM from controls.", "mechanism": "GDM is associated with specific changes in IgG N-glycan structures, notably FA2B and A2G2.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Reduced sialylation of IgG N-glycans increases Fc\u03b3RIIB signaling.", "mechanism": "Hyposialylated IgG activates Fc\u03b3RIIB, promoting insulin resistance in obesity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12608941" }, { "confidence": "high", "disease": "Low-grade Inflammation", "glycan_involvement": "Decrease in galactose and sialic acid content of IgG N-glycans.", "mechanism": "Agalactosylated and hyposialylated IgG N-glycans are increased in obesity, reflecting chronic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Altered N-glycosylation patterns correlate with insulin levels and resistance.", "mechanism": "Specific IgG N-glycan structures (FA2B, A2G2S2) are associated with metabolic parameters linked to T2DM.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Changes in infant IgG N-glycan profiles linked to maternal obesity.", "mechanism": "Children of obese mothers show altered IgG N-glycosylation, predisposing to metabolic syndrome.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "medium", "disease": "Obesity (offspring)", "glycan_involvement": "Reduced sialylation and altered glycan structures in infant IgG.", "mechanism": "Maternal obesity alters infant IgG N-glycosylation, potentially affecting immune development and obesity risk.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12608941" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM) (offspring)", "glycan_involvement": "Variation in sialylation and specific glycan peaks in infant IgG.", "mechanism": "Infants of GDM mothers show distinct IgG N-glycan profiles compared to controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "high", "disease": "Inflammatory Processes", "glycan_involvement": "N-glycosylation changes serve as indicators of inflammatory status.", "mechanism": "Altered IgG N-glycosylation (decreased sialylation, increased fucosylation) indicates ongoing inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12608941" }, { "confidence": "high", "disease": "Obesity-induced Insulin Resistance", "glycan_involvement": "Reduced sialylation increases Fc\u03b3RIIB-mediated signaling.", "mechanism": "Hyposialylated IgG acts as a ligand for Fc\u03b3RIIB, driving insulin resistance in obesity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12608941" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Truncated O-glycans (Tn, STn), sialylation", "mechanism": "Aberrant O-glycosylation (Tn, STn) creates a glycan shield, masking peptide epitopes and engaging inhibitory Siglec receptors, promoting immune evasion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "O-glycosylation, terminal sialylation", "mechanism": "Sialylated O-glycans on MUC16 engage Siglec-7/9 on NK and T cells, leading to immune suppression and T cell exhaustion.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "N-glycosylation", "mechanism": "N-glycosylation stabilizes PD-L1 on the cell surface, enhancing immune checkpoint function and inhibiting cytotoxic T cell activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation at Ser552 stabilizes \u03b2-catenin, promoting Wnt signaling, immune evasion, and altering antigen presentation.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC12609290" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Citrullination (not a glycan, but PTM discussed in glycoprotein context)", "mechanism": "PAD4-mediated citrullination creates neoepitopes, which can be targeted by vaccines to elicit immune responses.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Phosphorylation (not a glycan, but PTM discussed in glycoprotein context)", "mechanism": "Phosphorylation at Ser419 enhances antigen processing and MHC-I presentation, increasing immune visibility.", "protein": "Enolase 1 (ENO1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "medium", "disease": "Metastatic pancreatic cancer", "glycan_involvement": "Citrullination (PTM)", "mechanism": "PAD4-driven citrullination at Arg38 promotes NET formation, facilitating metastasis and immune exclusion.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12609290" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Sialylation", "mechanism": "Sialylated glycoform serves as a diagnostic biomarker; its levels reflect tumor-specific glycosylation.", "protein": "CA19-9 (Sialyl-Lewis A antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12609290" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "N-glycosylation (implied)", "mechanism": "Hyperacetylation and subsequent ubiquitination expose cryptic oncoprotein clients as immunogenic targets; glycosylation status may affect stability.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609290" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Potential glycosylation/S-nitrosylation", "mechanism": "Supports EMT and metastasis; glycosylation status under hypoxic stress may modulate immune recognition (mechanism not fully characterized).", "protein": "Annexin A2", "relationship_type": "causal", "source_pmcid": "PMC12609290" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "GP2 is a glycosylated surface protein; glycosylation is essential for cell sorting and immune recognition.", "mechanism": "Used as a surface marker to purify pancreatic progenitors, eliminating teratoma risk in \u03b2-cell replacement therapy.", "protein": "Glycoprotein 2 (GP2)", "protein_enriched": { "function": "Functions as an intestinal M-cell transcytotic receptor specific for type-I-piliated bacteria that participates in the mucosal immune response toward these bacteria. At the apical membrane of M-cells ", "gene_name": "GP2", "glycan_count": 8, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G11314AS", "G36379GD", "G57317CE", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G62765YT" ], "uniprot_id": "P55259" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609413" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation is critical for receptor folding, stability, and signaling.", "mechanism": "Mutations or impaired phosphorylation lead to insulin resistance.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12609413" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "GLP-1 receptor agonists enhance insulin secretion and glycemic control.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609413" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Adiponectin is heavily glycosylated; glycosylation is required for multimerization and bioactivity.", "mechanism": "Gene therapy increases adiponectin, improving insulin sensitivity and glucose homeostasis.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation modulates IRS-1 stability and interactions.", "mechanism": "Impaired phosphorylation and signaling contribute to insulin resistance.", "protein": "IRS-1", "relationship_type": "causal", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation is required for proper trafficking to the plasma membrane.", "mechanism": "Restoration of GLUT4 expression improves glucose uptake in muscle.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Neonatal diabetes", "glycan_involvement": "PDX1 is not a classical glycoprotein but may be regulated by glycosylation-related pathways.", "mechanism": "Mutations in PDX1 cause \u03b2-cell dysfunction; gene therapy restores function.", "protein": "PDX1", "protein_enriched": { "function": "Activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. Particularly involved in glucose-dependent regulation of insulin gene transcr", "gene_name": "PDX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P52945" }, "relationship_type": "causal", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Potential regulation by glycosylation; not a classical glycoprotein.", "mechanism": "Delivery of MAFA reprograms \u03b1-cells to \u03b2-like cells, restoring insulin production.", "protein": "MAFA", "protein_enriched": { "function": "Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylate", "gene_name": "KDM2B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q8NHM5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "GLP-1 is a peptide hormone; glycosylation may affect stability.", "mechanism": "GLP-1 gene delivery or mRNA therapy increases insulin secretion and lowers glucose.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609413" }, { "confidence": "medium", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Glycosylation modulates cytokine secretion and receptor interactions.", "mechanism": "Elevated TNF-\u03b1 promotes inflammation and impairs healing; siRNA silencing improves outcomes.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12609413" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation critical for integrin function and ligand binding.", "mechanism": "Upregulated in TEPs; mediates platelet aggregation and tumor\u2013platelet bridging, promoting metastasis.", "protein": "ITGA2B", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Associates with glycoprotein complexes; glycosylation affects cytoskeletal interactions.", "mechanism": "Upregulated in TEPs; regulates cytoskeletal remodeling and platelet activation, facilitating metastasis.", "protein": "FLNA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Interacts with glycoprotein receptors; glycosylation modulates signaling.", "mechanism": "Central adaptor in ITAM and other signaling pathways; modulates platelet activation and cancer\u2013platelet crosstalk.", "protein": "GRB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation essential for IgG binding and receptor function.", "mechanism": "Mediates platelet activation via tumor-derived IgG/immune complexes; promotes immunothrombosis and metastasis.", "protein": "FCGR2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation affects processing and function.", "mechanism": "Upregulated in TEPs; involved in ECM interactions and platelet-mediated thrombus formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation modulates cell\u2013cell interaction.", "mechanism": "Upregulated in TEPs; promotes cell adhesion and migration.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC12609506" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation required for surface expression and function.", "mechanism": "Upregulated in TEPs; mediates platelet adhesion and aggregation.", "protein": "GP1BB", "relationship_type": "causal", "source_pmcid": "PMC12609506" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates immune interactions.", "mechanism": "Strongly upregulated in TEPs; may support immune evasion and metastasis.", "protein": "PSG2", "relationship_type": "biomarker", "source_pmcid": "PMC12609506" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation critical for ECM assembly.", "mechanism": "Upregulated in TEPs; involved in ECM\u2013receptor interactions and metastasis.", "protein": "LAMB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N- and O-glycosylation modulate ECM binding.", "mechanism": "Upregulated in TEPs; promotes ECM remodeling and tumor cell adhesion.", "protein": "FN1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12609506" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation critical for CD31 function and stability.", "mechanism": "Decreased CD31 marks loss of endothelial phenotype during EndMT.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "high", "disease": "Endothelial-to-mesenchymal transition (EndMT)", "glycan_involvement": "O-glycosylation modulates filament assembly and cell migration.", "mechanism": "Upregulated vimentin indicates mesenchymal transition and fibrogenic activation.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "O-glycosylation affects contractile function.", "mechanism": "Increased \u03b1-SMA marks myofibroblast activation and fibrosis.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation essential for ECM binding and stability.", "mechanism": "Reduced dystroglycan disrupts membrane integrity, promoting fibrosis.", "protein": "Dystroglycan (\u03b2-dystroglycan)", "relationship_type": "causal", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Interacts with glycoprotein complex; glycosylation affects complex assembly.", "mechanism": "Loss of dystrophin destabilizes cardiomyocyte membrane, facilitating fibrotic remodeling.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Downregulation impairs membrane stability, contributing to fibrosis.", "protein": "Sarcoglycans (\u03b1, \u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation modulates integrin binding.", "mechanism": "Reduced talin disrupts cytoskeletal signaling, promoting remodeling.", "protein": "Talin", "protein_enriched": { "function": "High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co", "gene_name": "TLN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y490" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation influences focal adhesion dynamics.", "mechanism": "Loss of vinculin impairs cell adhesion and mechanical stability.", "protein": "Vinculin", "protein_enriched": { "function": "Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex.", "gene_name": "VCL", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G83460ZZ", "G49108TO" ], "uniprot_id": "P18206" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609725" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "N-glycosylation regulates secretion and activity.", "mechanism": "Upregulated MMP3 drives ECM degradation and remodeling.", "protein": "MMP3", "protein_enriched": { "function": "Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activa", "gene_name": "MMP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P08254" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12609725" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "Elevated MMP9 promotes matrix breakdown and fibrotic progression.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12609725" }, { "confidence": "medium", "disease": "PSP-P", "glycan_involvement": "Transferrin is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Elevated serum transferrin levels in PSP-P compared to controls; may reflect compensatory neuroprotective response via modulation of microglial phenotype.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "medium", "disease": "PSP-RS", "glycan_involvement": "Glycosylation required for transferrin's iron-binding and transport properties.", "mechanism": "Serum transferrin levels are higher in PSP-RS than controls; may indicate compensatory failure or different neurodegenerative mechanism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "low", "disease": "CBS", "glycan_involvement": "Glycosylation affects transferrin's renal handling and stability.", "mechanism": "Serum transferrin levels in CBS are lower than PSP subtypes and controls; urinary transferrin may reflect subclinical renal involvement.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Polymorphisms may affect glycosylation and iron-binding.", "mechanism": "Certain transferrin alleles (e.g., C2) increase AD risk, possibly via iron-mediated oxidative stress.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "causal", "source_pmcid": "PMC12609891" }, { "confidence": "medium", "disease": "Neurodegeneration (general)", "glycan_involvement": "Glycosylation required for transferrin's interaction with microglia.", "mechanism": "Transferrin promotes neuron survival and anti-inflammatory microglial M2 phenotype.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "medium", "disease": "PSP-RS", "glycan_involvement": "Glycosylation critical for VCAM-1's adhesive function.", "mechanism": "Serum VCAM-1 elevated in PSP-RS compared to controls; suggests neuroinflammatory involvement.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "low", "disease": "CBS", "glycan_involvement": "Glycosylation status may affect VCAM-1 shedding and function.", "mechanism": "VCAM-1 levels in CBS similar to controls; may indicate less neuroinflammatory involvement.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation modulates VCAM-1's immune interactions.", "mechanism": "Serum VCAM-1 increased in schizophrenia; supports neuroinflammatory hypothesis.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "low", "disease": "Chronic Traumatic Encephalopathy", "glycan_involvement": "Glycosylation affects VCAM-1's role in leukocyte migration.", "mechanism": "VCAM-1 associated with microglial activity and p-tau accumulation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12609891" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Cav is a membrane glycoprotein; glycosylation may affect peptide binding and endocytosis.", "mechanism": "Walnut-derived peptides bind Cav to facilitate BBB penetration, enabling delivery of neuroprotective agents.", "protein": "Caveolin (Cav)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "MMP-9 is glycosylated; glycosylation modulates secretion and activity.", "mechanism": "Walnut peptide TWLPLPR inhibits MMP-9, protecting BBB integrity and alleviating cognitive deficits.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "NF-\u03baB activity can be modulated by glycoprotein signaling.", "mechanism": "EVSGPGLSPN inhibits NF-\u03baB/caspase pathway, reducing neuroinflammation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "low", "disease": "Oxidative stress-related brain injury", "glycan_involvement": "PPAR\u03b3 function can be influenced by glycosylation of interacting proteins.", "mechanism": "YVPFPLP forms a complex with PPAR\u03b3, improving glutamate-induced excitotoxicity.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12610161" }, { "confidence": "medium", "disease": "Oxidative stress-related brain injury", "glycan_involvement": "Glycosylation of Cav may regulate peptide-mediated endocytosis.", "mechanism": "Tyrosine-rich peptides bind Cav, enhancing BBB penetration and reducing ROS in neurons.", "protein": "Caveolin (Cav)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "medium", "disease": "Insulin resistance-induced cognitive deficits", "glycan_involvement": "Glycosylation affects MMP-9 stability and function.", "mechanism": "TWLPLPR inhibits MMP-9, protecting BBB and improving cognition in insulin resistance models.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "low", "disease": "Cognitive impairment", "glycan_involvement": "Cav glycosylation may modulate transporter function.", "mechanism": "Peptide-mediated Cav targeting enhances brain delivery of neuroprotective peptides.", "protein": "Caveolin (Cav)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12610161" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Glycosylation required for secretion and stability; glycan moieties may influence immune recognition.", "mechanism": "Reflects neuroinflammation and astrocyte/macrophage activation; levels increase post-thrombolysis indicating tissue repair/remodeling.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Glycosylation essential for function and chemotactic activity.", "mechanism": "Elevated pre-thrombolysis; reflects early monocyte recruitment, cerebrovascular stress, and acute inflammation.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may modulate interaction with extracellular matrix and immune cells.", "mechanism": "Promotes atherosclerotic plaque formation and is upregulated in vascular inflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation affects stability and extracellular localization.", "mechanism": "Elevated in degenerative joint disease; involved in tissue remodeling.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation required for immune modulation.", "mechanism": "Upregulated in neuroinflammatory conditions; may reflect immune cell recruitment.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "Glycosylation influences protein-protein interactions.", "mechanism": "Elevated in neurodegeneration; may participate in monocyte chemotaxis and angiogenesis.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "Glycosylation impacts extracellular function.", "mechanism": "Increased expression in neurodegenerative disease; role in tissue remodeling.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12610758" }, { "confidence": "high", "disease": "Ischemic Stroke (IS)", "glycan_involvement": "Adduct formation may alter glycoprotein structure/function.", "mechanism": "Elevated during acute IS; mediates oxidative damage to mitochondria and promotes inflammation.", "protein": "4-HNE-protein adducts", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "Modification of glycoproteins may trigger autoimmune responses.", "mechanism": "High plasma levels correlate with neurodegeneration and oxidative stress.", "protein": "4-HNE-protein adducts", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12610758" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Adducts may affect glycoprotein-mediated cell signaling.", "mechanism": "Involved in pathogenesis via oxidative stress and protein modification.", "protein": "4-HNE-protein adducts", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12610758" }, { "confidence": "high", "disease": "GNE myopathy", "glycan_involvement": "Defective glycosylation (sialylation) of muscle glycoproteins.", "mechanism": "Mutations in GNE impair sialic acid biosynthesis, leading to muscle pathology.", "protein": "GNE", "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "medium", "disease": "Titinopathy", "glycan_involvement": "Glycosylation may affect titin stability and muscle integrity.", "mechanism": "Mutations in titin disrupt sarcomere structure and function.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "medium", "disease": "Distal myopathy", "glycan_involvement": "Impaired sialylation of muscle glycoproteins.", "mechanism": "GNE mutations can present as distal muscle weakness.", "protein": "GNE", "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "medium", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Altered glycosylation of muscle proteins.", "mechanism": "Some GNE mutations may manifest with limb-girdle pattern.", "protein": "GNE", "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "low", "disease": "Congenital myopathy", "glycan_involvement": "Defective glycosylation in muscle development.", "mechanism": "Rare GNE variants may cause congenital myopathy.", "protein": "GNE", "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "low", "disease": "Congenital muscular dystrophy", "glycan_involvement": "Impaired glycosylation of muscle membrane proteins.", "mechanism": "GNE mutations can rarely present as congenital muscular dystrophy.", "protein": "GNE", "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "low", "disease": "Limb-girdle muscular dystrophy (LGMD)", "glycan_involvement": "Potential impact on glycosylation-mediated stability.", "mechanism": "Titin mutations can cause LGMD phenotype.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "causal", "source_pmcid": "PMC12611062" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation affects ECM structure and cell-matrix interactions.", "mechanism": "Upregulated in DMD muscle; contributes to ECM expansion and fibrosis.", "protein": "Collagen Type XVIII Alpha 1 Chain (COL18A1)", "protein_enriched": { "function": "Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube", "gene_name": "COL18A1", "glycan_count": 21, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G31852PQ", "G53075ES", "G56518TU", "G62765YT", "G64527OM", "G69521XL", "G70232NH", "G82443XX", "G89827JR", "G49108TO", "G57321FI", "G29068FM", "G43417UB", "G00031MO", "G29931IJ", "G53434XO", "G58001LT", "G27391WQ", "G88713AC", "G45504EY" ], "uniprot_id": "P39060" }, "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation modulates collagen stability and ECM assembly.", "mechanism": "Upregulated in DMD; involved in ECM remodeling and fibrosis.", "protein": "Collagen Type VI Alpha 2 Chain (COL6A2)", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation influences ECM deposition.", "mechanism": "Upregulated in DMD; marker of fibrotic remodeling.", "protein": "Collagen Type VI Alpha 3 Chain (COL6A3)", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Polysialylation (O-glycosylation) critical for cell-cell adhesion and muscle regeneration.", "mechanism": "Downregulated in DMD; indicates impaired muscle regeneration and satellite cell commitment.", "protein": "Neural Cell Adhesion Molecule 1 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation may affect membrane localization.", "mechanism": "Upregulated in DMD; involved in sarcolemma repair and cytoskeletal organization.", "protein": "Annexin A2", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation may modulate membrane interactions.", "mechanism": "Upregulated in DMD; associated with sarcolemma and ECM.", "protein": "Annexin A6", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "ANXA6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08133" }, "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation required for ECM function.", "mechanism": "Upregulated in DMD; ECM glycoprotein involved in elastic fiber assembly.", "protein": "Emilin-1", "protein_enriched": { "function": "Involved in elastic and collagen fibers formation. It is required for EFEMP2 deposition into the extracellular matrix, and collagen network assembly and cross-linking via protein-lysine 6-oxidase/LOX ", "gene_name": "EMILIN1", "glycan_count": 60, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G57321FI", "G29068FM", "G44753VC", "G45395BF", "G73027HY", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G23863VK", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G39446WN", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G46691LC", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G84225JN", "G84452RH", "G90382BL", "G90659AW", "G95177YH", "G37412TK", "G43769HG", "G48414YA", "G49955PK", "G50045TK", "G62765YT", "G76295SF", "G80920RR", "G83646BJ", "G85282JO", "G86182NS", "G95865ZB", "G98611JV", "G49108TO" ], "uniprot_id": "Q9Y6C2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation essential for basement membrane interactions.", "mechanism": "Upregulated in DMD; basement membrane glycoprotein, marker of ECM remodeling.", "protein": "Nidogen-2", "protein_enriched": { "function": "Cell adhesion glycoprotein which is widely distributed in basement membranes. Binds to collagens I and IV, to perlecan and to laminin 1. Does not bind fibulins. It probably has a role in cell-extracel", "gene_name": "NID2", "glycan_count": 114, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G29068FM", "G43417UB", "G27391WQ", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G57321FI", "G49108TO", "G58498GJ", "G20528HD", "G23863VK", "G34029GR", "G84452RH", "G02815KT", "G04657PL", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10488MI", "G10819WX", "G11314AS", "G13131HA", "G14972EH", "G15664MX", "G16125XL", "G20706XG", "G23505EP", "G23719VF", "G25079LO", "G27058EU", "G27126ED", "G27915IV", "G29545VG", "G34989PA", "G35541EV", "G36379GD", "G37509XX", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46687AB", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G59626AS", "G60033FS", "G60834IK", "G65092SV", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72790NZ", "G73968GN", "G76295SF", "G77669RF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83646BJ", "G84225JN", "G84862VB", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G88891KO", "G90382BL", "G90659AW", "G93718GY", "G95177YH", "G00912UN", "G02886BB", "G03382KH", "G07755XJ", "G10486CT", "G14994KB", "G17208MA", "G27947YN", "G28622IK", "G31852PQ", "G40574BA", "G43669FQ", "G43769HG", "G45504EY", "G61256FT", "G62765YT", "G63980BQ", "G70223PD", "G72747WU", "G77547TA", "G82443XX", "G83460ZZ", "G85554PZ", "G86182NS", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G98611JV", "G71142DF" ], "uniprot_id": "Q14112" }, "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation affects receptor binding and clearance.", "mechanism": "Upregulated in DMD; involved in lipid transport and ECM interactions.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Upregulated in DMD; collagen-specific chaperone, marker of ECM remodeling.", "protein": "Serpin H1", "relationship_type": "biomarker", "source_pmcid": "PMC12611083" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Multimeric glycosylation critical for VWF function and clearance.", "mechanism": "Elevated VWF promotes platelet adhesion and aggregation, contributing to thrombosis in IBD.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation required for ligand binding and cell surface expression.", "mechanism": "Upregulated on activated platelets, mediates platelet-leukocyte aggregates and inflammation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation affects TF stability and activity.", "mechanism": "Upregulated TF initiates extrinsic coagulation, increasing thrombin and fibrin formation.", "protein": "Tissue factor", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12611498" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation modulates receptor binding and immune signaling.", "mechanism": "Platelet CD40L interacts with endothelial CD40, upregulating adhesion molecules and cytokines.", "protein": "CD40 ligand", "relationship_type": "causal", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Sialylated O-glycans essential for P-selectin binding.", "mechanism": "Mediates platelet-leukocyte interactions, amplifying inflammation and thrombosis.", "protein": "P-selectin glycoprotein ligand-1", "relationship_type": "causal", "source_pmcid": "PMC12611498" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation required for receptor function and protein C binding.", "mechanism": "Reduced EPCR impairs protein C activation, decreasing anticoagulant and fibrinolytic capacity.", "protein": "Endothelial protein C receptor", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "N-glycosylation influences fibrin polymerization and clot structure.", "mechanism": "Elevated fibrinogen reflects ongoing coagulation activation and contributes to clot formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12611498" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation modulates ligand binding and receptor activation.", "mechanism": "Upregulated on platelets, enhances aggregation via fibrinogen and VWF binding.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12611498" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "O-glycosylation affects matrix interactions and angiogenic activity.", "mechanism": "Secreted by activated platelets, promotes endothelial damage and vascular remodeling.", "protein": "Thrombospondin-1", "relationship_type": "causal", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation influences PAI-1 stability and inhibitory activity.", "mechanism": "Elevated PAI-1 inhibits fibrinolysis, prolonging clot stability and increasing thrombotic risk.", "protein": "Plasminogen activator inhibitor-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12611498" }, { "confidence": "high", "disease": "Cryptococcosis", "glycan_involvement": "Recognizes fungal glycan epitopes (GXM, \u03b2-glucans) via multivalent binding.", "mechanism": "IgM binds GXM and \u03b2-glucans on Cryptococcus neoformans, activates complement, inhibits titan cell formation, and promotes fungal clearance.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12611827" }, { "confidence": "high", "disease": "Candidiasis", "glycan_involvement": "Targets \u03b2-mannan and glycoprotein epitopes on fungal cell wall.", "mechanism": "IgM binds \u03b2-mannan and germ tube antigens, opsonizes Candida albicans, suppresses filamentation, and enhances phagocytosis.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12611827" }, { "confidence": "high", "disease": "Pneumocystis pneumonia", "glycan_involvement": "Binds conserved fungal polysaccharides (\u03b2-glucan, chitin).", "mechanism": "IgM recognizes \u03b2-1,3-glucan and chitin on Pneumocystis murina, triggers complement, and accelerates fungal clearance.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12611827" }, { "confidence": "medium", "disease": "Aspergillosis", "glycan_involvement": "Targets fungal glycoprotein antigens for selective delivery.", "mechanism": "IgM monoclonal antibody conjugated to alliinase selectively targets and kills Aspergillus fumigatus in vivo.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. 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In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", 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"G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12611827" }, { "confidence": "medium", "disease": "Candidiasis", "glycan_involvement": "Als3p is a cell wall glycoprotein involved in virulence.", "mechanism": "IgM monoclonal antibody C7 targets Als3p, inhibits adhesion, filamentation, and kills Candida albicans.", "protein": "Als3p", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q59XU7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12611827" }, { "confidence": "medium", "disease": "Candidiasis", "glycan_involvement": "Enolase is a glycoprotein exposed on fungal surface.", "mechanism": "IgM monoclonal antibody C7 cross-reacts with enolase, contributing to antifungal activity.", "protein": "Enolase", "protein_enriched": { "function": "", "gene_name": "ENO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00924" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12611827" }, { "confidence": "high", "disease": "Invasive fungal diseases", "glycan_involvement": "Recognizes fungal glycan motifs for immune activation.", "mechanism": "MBL binds mannan and N-acetylglucosamine on fungal pathogens, activates lectin complement pathway.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "protective", "source_pmcid": "PMC12611827" }, { "confidence": "high", "disease": "Opportunistic mycoses", "glycan_involvement": "\u03b2-glucan is a conserved fungal cell wall polysaccharide.", "mechanism": "Serum IgM specific for \u03b2-glucan serves as a marker of exposure and immune activation in fungal infections.", "protein": "\u03b2-glucan", "relationship_type": "biomarker", "source_pmcid": "PMC12611827" }, { "confidence": "high", "disease": "Multidrug resistance in cancer", "glycan_involvement": "Glycosylation stabilizes protein and affects substrate recognition.", "mechanism": "Overexpression of p-glycoprotein leads to efflux of chemotherapeutic agents, causing resistance.", "protein": "p-glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12613017" }, { "confidence": "medium", "disease": "Chronic inflammatory diseases", "glycan_involvement": "Glycosylation modulates transporter function.", "mechanism": "Herbal inhibitors targeting p-glycoprotein hotspots may reduce drug resistance in inflammation.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation influences transporter activity.", "mechanism": "Herbal bioactives may inhibit p-glycoprotein, improving drug efficacy in diabetes.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "medium", "disease": "Rheumatism", "glycan_involvement": "Glycosylation affects substrate binding.", "mechanism": "Herbal inhibitors may overcome p-glycoprotein-mediated resistance in rheumatic conditions.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "medium", "disease": "Infections", "glycan_involvement": "Glycosylation modulates efflux activity.", "mechanism": "Herbal compounds targeting p-glycoprotein may enhance antimicrobial drug retention.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation influences transporter stability.", "mechanism": "Herbal bioactives (e.g., coniferol) interact with p-glycoprotein, potentially improving drug response in cardiovascular conditions.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "low", "disease": "Jaundice", "glycan_involvement": "Glycosylation affects substrate specificity.", "mechanism": "Ipomoea aquatica bioactives inhibit p-glycoprotein, aiding detoxification in jaundice.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "low", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation impacts transporter function.", "mechanism": "Herbal inhibitors may modulate p-glycoprotein to improve glycemic control.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "low", "disease": "Infertility", "glycan_involvement": "Glycosylation may influence tissue-specific activity.", "mechanism": "Abies webbiana bioactives may target p-glycoprotein, potentially affecting reproductive health.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "low", "disease": "Neurological disorders", "glycan_involvement": "Glycosylation modulates blood-brain barrier transport.", "mechanism": "Centella asiatica bioactives (altretamine) interact with p-glycoprotein, possibly enhancing CNS drug delivery.", "protein": "p-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613017" }, { "confidence": "high", "disease": "Giant Cell Arteritis (GCA)", "glycan_involvement": "SAA is a glycoprotein; glycosylation may affect stability and receptor interactions.", "mechanism": "SAA is highly expressed in inflamed temporal arteries and plasma; induces IL-6 via TLR2/4 activation.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "high", "disease": "Giant Cell Arteritis (GCA)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation influences immune cell activation.", "mechanism": "Fibrinogen is overexpressed in inflamed arteries and plasma; stimulates IL-6 production via TLR4.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Giant Cell Arteritis (GCA)", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement reported.", "mechanism": "HMGB-1 is released from damaged cells, activates TLR2/4 and RAGE, promoting inflammation.", "protein": "High Mobility Group Box 1 (HMGB-1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Giant Cell Arteritis (GCA)", "glycan_involvement": "Heavily N-glycosylated; glycosylation affects drug efflux function.", "mechanism": "Overexpression in arteries may contribute to glucocorticoid resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12613359" }, { "confidence": "high", "disease": "Cranial GCA (C-GCA)", "glycan_involvement": "N-glycosylation required for proper folding and ligand binding.", "mechanism": "TLR2 is highly upregulated in inflamed arteries, mediates DAMP-induced inflammation.", "protein": "Toll-like receptor 2 (TLR2)", "protein_enriched": { "function": "Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bac", "gene_name": "TLR2", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G08146BT", "G22310AV", "G71146HJ", "G75983OB", "G00912UN", "G25451PN", "G27058EU", "G40926MX", "G45395BF", "G45495MK", "G62765YT", "G70101JE", "G80920RR", "G83229XP", "G84452RH", "G83460ZZ" ], "uniprot_id": "O60603" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "high", "disease": "Cranial GCA (C-GCA)", "glycan_involvement": "N-glycosylation essential for cell surface expression and ligand recognition.", "mechanism": "TLR4 is overexpressed in inflamed arteries, mediates response to fibrinogen and HMGB-1.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Cranial GCA (C-GCA)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "TLR7 is highly expressed at sites of arterial stenosis, may mediate viral or endogenous RNA-induced inflammation.", "protein": "Toll-like receptor 7 (TLR7)", "protein_enriched": { "function": "Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:14976261, PubMed:32433612). Controls host immune response against pathogens through recognition of uridine-containing s", "gene_name": "TLR7", "glycan_count": 3, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G45395BF", "G57776ZS", "G63041LO" ], "uniprot_id": "Q9NYK1" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Cranial GCA (C-GCA)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "TLR8 is upregulated in inflamed arteries, especially in macrophages and smooth muscle cells.", "protein": "Toll-like receptor 8 (TLR8)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Polymyalgia Rheumatica (PMR)", "glycan_involvement": "Glycosylation may modulate inflammatory activity.", "mechanism": "SAA levels are elevated in PMR plasma and arteries, correlating with CRP/ESR.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "medium", "disease": "Polymyalgia Rheumatica (PMR)", "glycan_involvement": "N-glycosylation modulates immune activation.", "mechanism": "Fibrinogen levels are elevated in PMR plasma and arteries, correlating with CRP/ESR.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12613359" }, { "confidence": "high", "disease": "human metapneumovirus infection", "glycan_involvement": "Glycosylation and sequence duplications in G glycoprotein increase antigenic diversity and may affect immune evasion.", "mechanism": "G glycoprotein mediates viral attachment and entry into host respiratory epithelial cells, contributing to infection.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "causal", "source_pmcid": "PMC12613910" }, { "confidence": "high", "disease": "human metapneumovirus infection", "glycan_involvement": "Sequence duplications in G glycoprotein (111-nt and 180-nt) alter glycosylation patterns, serving as molecular markers.", "mechanism": "Genetic diversity and duplications in G glycoprotein are used for subtyping and genomic surveillance of HMPV strains.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "biomarker", "source_pmcid": "PMC12613910" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Upregulation of sialylated and fucosylated N-glycans, increased branching, and bisecting GlcNAc structures.", "mechanism": "Altered N-glycan composition and structure in serum glycoproteins are associated with HCC pathogenesis and progression.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Liver cirrhosis (LC)", "glycan_involvement": "Upregulation of sialylated and fucosylated N-glycans; similar glycosylation changes as HCC.", "mechanism": "Global shifts in serum N-glycan profiles reflect progression from benign to malignant liver disease.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Minor upregulation of sialylated/fucosylated N-glycans compared to malignant stages.", "mechanism": "N-glycan profiles in CHB overlap with healthy controls, but show early changes in glycosylation.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered N-glycosylation patterns on IgG during disease progression.", "mechanism": "IgG glycopeptide analyses capture fine-scale glycosylation dynamics during HCC progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP glycosylation not specifically analyzed in this study.", "mechanism": "AFP is a traditional biomarker for HCC, but has limited diagnostic performance compared to N-glycan panel.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "12 sialylated N-glycan isomers, especially \u03b12-3-linked, are upregulated in HCC.", "mechanism": "Specific sialylated N-glycan isomers (\u03b12-3/\u03b12-6 linkages) show significant differential expression in HCC.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Liver cirrhosis (LC)", "glycan_involvement": "Shared upregulation of \u03b12-3/\u03b12-6 sialylated N-glycans in LC and HCC.", "mechanism": "Sialylated N-glycan isomers also show upregulation in LC, complicating differentiation from HCC.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Increased fucosylation and sialylation promote cell adhesion, metastatic potential, and immune modulation.", "mechanism": "Altered glycosylation (fucosylation, sialylation) may contribute to tumor growth, metastasis, and immune evasion.", "protein": "Serum glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Combined upregulation of high-mannose, fucosylated, sialylated, and bisected N-glycans.", "mechanism": "Panel of 24 N-glycans provides superior diagnostic accuracy for distinguishing benign vs. malignant liver disease.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Differential expression of \u03b12-3 vs. \u03b12-6 sialylated N-glycan isomers.", "mechanism": "Isomer-specific analysis of N-glycans enhances diagnostic specificity for early HCC detection.", "protein": "Serum glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12614178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Galactose/lactose ligands recognized by ASGPR enhance selective uptake.", "mechanism": "ASGPR is overexpressed in HCC cells and mediates uptake of galactose/lactose-modified nanoplatforms for targeted drug delivery.", "protein": "Asialoglycoprotein receptor (ASGPR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Hyaluronic acid (HA) binds CD44, mediating selective targeting.", "mechanism": "CD44 is overexpressed in breast cancer cells; HA-functionalized nanoplatforms target CD44 for imaging and drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "high", "disease": "Brain tumor/Stroke", "glycan_involvement": "Glucose conjugation enables GLUT-mediated transport.", "mechanism": "GLUTs are overexpressed in tumors and at the blood-brain barrier; glucose-modified nanoplatforms enhance uptake into tumor and brain tissue.", "protein": "Glucose transporter (GLUT) family", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "high", "disease": "Immune dysfunction (TAMs)", "glycan_involvement": "Mannose/galactose ligands mediate selective binding and immune modulation.", "mechanism": "CD206 is highly expressed on tumor-associated macrophages; mannose/galactose-modified nanoplatforms target and reprogram TAMs.", "protein": "CD206 (Mannose receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Leukemia (B cell)", "glycan_involvement": "Multivalent sialic acid ligands enhance binding and cytotoxicity.", "mechanism": "CD22 is overexpressed on B cells; \u03b1-2,6-sialyllactose-modified carbon dots bind and induce cytotoxicity in CD22+ B cells.", "protein": "Siglec-2 (CD22)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Brain tumor/Stroke", "glycan_involvement": "SX epitope mediates selectin binding.", "mechanism": "SX-modified MNPs bind E- and P-selectin on inflamed endothelium, enabling detection of endothelial activation after stroke.", "protein": "Sialyl Lewis X (SX)", "relationship_type": "biomarker", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Glucose ligand stabilizes QDs, sulfonamide enables CA IX targeting.", "mechanism": "CA IX is overexpressed in bladder cancer; glycodots with sulfonamide inhibitors selectively bind CA IX for imaging.", "protein": "Carbonic anhydrase IX (CA IX)", "protein_enriched": { "function": "Catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions)", "gene_name": "CA9", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB", "G57321FI", "G22768VO", "G49108TO" ], "uniprot_id": "Q16790" }, "relationship_type": "biomarker", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Glycopolymers mimic natural glycosaminoglycans to disrupt selectin binding.", "mechanism": "E-selectin mediates tumor cell-platelet adhesion; glycopolymer-grafted nanoplatforms inhibit this interaction, reducing metastasis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Immune dysfunction (TAMs)", "glycan_involvement": "Multivalent mannose presentation enhances DC-SIGN binding.", "mechanism": "DC-SIGN recognizes high-mannose glycans; glycodots with \u03b1-1,2-mannobiose modulate lectin interactions for immune targeting.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614179" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Dextran provides bacterial binding and nanoparticle stabilization.", "mechanism": "Dextran-coated magnetic nanoparticles capture and separate Mycobacterium tuberculosis for rapid diagnosis.", "protein": "Dextran-coated SPIO", "relationship_type": "diagnostic_tool", "source_pmcid": "PMC12614179" }, { "confidence": "high", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "O-glycosylation creates negatively charged, hydrated gel.", "mechanism": "Mucins form a glycosylated barrier preventing pneumococcal attachment and promoting clearance.", "protein": "Mucin proteins", "relationship_type": "protective", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "Glycosylation affects stability and mucosal transport.", "mechanism": "sIgA agglutinates pneumococcus and blocks epithelial attachment.", "protein": "Secretory IgA (sIgA)", "relationship_type": "protective", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Invasive pneumococcal disease", "glycan_involvement": "Polysaccharide structure and charge modulate interactions.", "mechanism": "Capsule enables evasion of mucus and immune clearance, facilitating invasion.", "protein": "Pneumococcal capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Binds mannose receptor (CD206, a glycoprotein) to modulate immune response.", "mechanism": "Toxin disrupts host cell membranes, triggers inflammation and cell death.", "protein": "Pneumolysin", "protein_enriched": { "function": "", "gene_name": "amy1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0C1B3" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "medium", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "Surface exposure regulated by capsule phase variation.", "mechanism": "Promotes epithelial attachment and immune evasion.", "protein": "PspC", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NY49" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "Targets lactose/N-acetyllactosamine on host glycoproteins.", "mechanism": "Degrades host glycans for nutrient acquisition and mediates attachment.", "protein": "BgaA (\u03b2-galactosidase)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NY50" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "Cleaves \u03b12\u20133/\u03b12\u20136-linked sialic acids on glycoproteins.", "mechanism": "Removes sialic acids from host glycoproteins, exposing underlying sugars for bacterial use.", "protein": "NanA (neuraminidase)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NY51" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "medium", "disease": "Nasopharyngeal colonisation", "glycan_involvement": "Acts on N-linked and O-linked glycans.", "mechanism": "Removes N-acetylglucosamine from host glycans, aiding nutrient acquisition.", "protein": "StrH (N-acetylglucosaminidase)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NY52" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Invasive pneumococcal disease", "glycan_involvement": "Glycosylation affects protease susceptibility.", "mechanism": "IgA1 protease cleaves sIgA, reducing its protective function and facilitating invasion.", "protein": "Secretory IgA (sIgA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Invasive pneumococcal disease", "glycan_involvement": "Interacts with glycosylated receptors (CD206).", "mechanism": "Promotes inflammation and transmission, but also faster clearance from nasopharynx.", "protein": "Pneumolysin", "protein_enriched": { "function": "", "gene_name": "amy1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0C1B3" }, "relationship_type": "causal", "source_pmcid": "PMC12614598" }, { "confidence": "high", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "PilQ is glycosylated; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Anti-PilQ antibodies elicited by vaccination correlate with protection and enhanced clearance of gonococci.", "protein": "PilQ", "protein_enriched": { "function": "E2 component of the 2-oxoglutarate dehydrogenase (OGDH) complex which catalyzes the second step in the conversion of 2-oxoglutarate to succinyl-CoA and CO(2)", "gene_name": "sucB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50993" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "PilC glycosylation may modulate immune recognition.", "mechanism": "Vaccination induces weak anti-PilC antibodies, potentially contributing to immune clearance.", "protein": "PilC", "protein_enriched": { "function": "", "gene_name": "lpd", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50994" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "Glycosylation status may influence VacJ immunogenicity.", "mechanism": "Antibodies against VacJ detected post-vaccination, suggesting a role in immune-mediated clearance.", "protein": "VacJ (MlaA)", "protein_enriched": { "function": "Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs", "gene_name": "rplP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5F5T4" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "MetQ is a lipoprotein; glycosylation may affect its immune profile.", "mechanism": "SC vaccination route induces anti-MetQ antibodies, possibly contributing to protection.", "protein": "MetQ", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5F7C7" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "PilE glycosylation may modulate antibody binding.", "mechanism": "IP vaccination induces anti-PilE antibodies, potentially enhancing opsonophagocytic killing.", "protein": "PilE", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50995" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "Glycosylation may affect MIP antigenicity.", "mechanism": "IP vaccination elicits anti-MIP antibodies, which may contribute to immune clearance.", "protein": "NGO1225 (MIP)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5F6C2" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "OmpU is a lipoprotein; glycosylation may influence immune recognition.", "mechanism": "Strong antibody responses to OmpU observed post-vaccination, suggesting a role in protection.", "protein": "OmpU (NGO1688)", "protein_enriched": { "function": "Catalyzes the transfer of an acyl group from acyl-phosphate (acyl-PO(4)) to glycerol-3-phosphate (G3P) to form lysophosphatidic acid (LPA). This enzyme utilizes acyl-phosphate as fatty acyl donor, but", "gene_name": "plsY", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5F8C7" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "FetA glycosylation may affect antigenicity.", "mechanism": "Antibodies to FetA detected after vaccination, possibly aiding in bacterial clearance.", "protein": "FetA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50996" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "low", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "BamA glycosylation may modulate immune response.", "mechanism": "Weaker antibody responses to BamA observed, may contribute to immune defense.", "protein": "BamA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50997" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "medium", "disease": "Neisseria gonorrhoeae infection (gonorrhea)", "glycan_involvement": "PorB is glycosylated; glycosylation may affect cross-reactivity and immune recognition.", "mechanism": "Low-level anti-PorB antibodies detected in all immunized mice; may contribute to cross-reactive protection.", "protein": "PorB", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50998" }, "relationship_type": "protective", "source_pmcid": "PMC12614976" }, { "confidence": "high", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "Increases high-mannose glycan structures on glycoproteins.", "mechanism": "Upregulated DPM1 promotes mannose-type N-glycosylation, reduces immune cell infiltration, and enhances cell migration.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "Increases complex N-glycan branching.", "mechanism": "Upregulated MGAT5 promotes \u03b21,6-GlcNAc branching, associated with immune evasion.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "Involved in early N-glycan biosynthesis.", "mechanism": "Upregulated ALG6 correlates with immunosuppression and altered glycosylation.", "protein": "ALG6", "protein_enriched": { "function": "Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)", "gene_name": "ALG6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9Y672" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "Initiates N-glycan precursor synthesis.", "mechanism": "Upregulated DPAGT1 correlates with reduced immune infiltration.", "protein": "DPAGT1", "protein_enriched": { "function": "General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. Ma", "gene_name": "USO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "High-mannose N-glycosylation at lysosomal sites.", "mechanism": "Increased high-mannose glycoforms of LAMP1 in tumors, linked to lysosomal pathway enrichment.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). 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"G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "High-mannose N-glycosylation.", "mechanism": "Upregulated high-mannose glycoforms in tumor tissue, associated with lysosomal function.", "protein": "ASAH1", "protein_enriched": { "function": "Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:11451951, PubMed:15655246, PubMed:26898341, PubMed:36752535, Pub", "gene_name": "ASAH1", "glycan_count": 121, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G07246CJ", "G10486CT", "G11101UV", "G11870QZ", "G12313PD", "G18647XP", "G20210JR", "G26330YA", "G28541PG", "G28681TP", "G31852PQ", "G33416PL", "G34029GR", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G43223CG", "G46503DX", "G49955PK", "G50282JC", "G57776ZU", "G62765YT", "G62894KT", "G63136LV", "G64409MC", "G64527OM", "G70375MX", "G72747WU", "G80920RR", "G82119TF", "G82463GQ", "G83460ZZ", "G84349RE", "G84820NF", "G85282JO", "G85677PP", "G88891KO", "G90575OW", "G90659AW", "G92050GC", "G92275SC", "G95865ZB", "G00273SJ", "G00406II", "G00912UN", "G01485JJ", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08918WF", "G10846ZT", "G11314AS", "G13191RB", "G14669DU", "G14972EH", "G17208MA", "G22310AV", "G22572EH", "G23294PN", "G23719VF", "G24528MX", "G27058EU", "G31028YV", "G35029YA", "G37412TK", "G40206WX", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G45395BF", "G45504EY", "G46524LG", "G47644PP", "G48414YA", "G49018RC", "G49642SA", "G50757KG", "G51640FO", "G51653BI", "G54010QB", "G57317CE", "G58954YZ", "G59626AS", "G60923RB", "G65184UU", "G69521XL", "G70101JE", "G70619PT", "G72291OX", "G72787SB", "G72790NZ", "G73968GN", "G74724QE", "G82830MN", "G83646BJ", "G85269DF", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G90734RJ", "G90787TS", "G92135MA", "G92406TI", "G94470IW", "G96091TT", "G98611JV", "G49108TO", "G02528FI", "G47702MW", "G77547TA" ], "uniprot_id": "Q13510" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "High-mannose N-glycosylation at N830 and N515.", "mechanism": "Mannose-rich glycoforms of HYOU1 correlate with immune cell infiltration and ER stress pathways.", "protein": "HYOU1", "protein_enriched": { "function": "Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) ", "gene_name": "HYOU1", "glycan_count": 145, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G15664MX", "G46503DX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G73968GN", "G80920RR", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G25079LO", "G25637MV", "G28541PG", "G31852PQ", "G35029YA", "G39188ZX", "G39446WN", "G41247ZX", "G47644PP", "G50282JC", "G51044QT", "G59924QI", "G64409MC", "G85554PZ", "G88891KO", "G96430BV", "G49108TO", "G00406II", "G00912UN", "G03930BU", "G04657PL", "G06356OH", "G07755XJ", "G10486CT", "G11629QQ", "G22310AV", "G23719VF", "G27058EU", "G28681TP", "G29511JR", "G31916IQ", "G37692EO", "G37881RL", "G40574BA", "G42124LM", "G48414YA", "G48584BU", "G49874UX", "G49955PK", "G57317CE", "G57888GL", "G59626AS", "G62894KT", "G70619PT", "G80333GO", "G83460ZZ", "G84452RH", "G87661QW", "G92050GC", "G95177YH", "G57321FI", "G01485JJ", "G10819WX", "G11314AS", "G14260UH", "G15127JD", "G18647XP", "G24528MX", "G30248BL", "G36379GD", "G40926MX", "G50757KG", "G54010QB", "G57776ZU", "G65000LJ", "G67164EE", "G68735SN", "G72197KC", "G72787SB", "G72790NZ", "G77547TA", "G83633GK", "G84349RE", "G85269DF", "G86182NS", "G90575OW", "G90659AW", "G92275SC", "G94854LT", "G29068FM", "G43417UB", "G02886BB", "G13694XX", "G23863VK", "G34617SM", "G39595FH", "G41882MT", "G46687AB", "G46902YN", "G49018RC", "G62461SM", "G64394MX", "G81263BG", "G93656SY", "G06247RL", "G23505EP", "G36670VW", "G70223PD", "G70232NH", "G74724QE", "G88374WZ", "G91473PK", "G10256JP", "G11870QZ", "G14669DU", "G14972EH", "G20210JR", "G23294PN", "G23432EQ", "G23984SE", "G33416PL", "G43089EG", "G76868JS", "G78787DI", "G05362KT", "G05962QB", "G11101UV", "G36442WJ", "G40206WX", "G46691LC", "G49589RB", "G56307ZW", "G63980BQ", "G68490OW", "G69521XL", "G85282JO", "G94470IW", "G10846ZT", "G41071NU", "G45504EY", "G50045TK", "G90734RJ", "G95865ZB" ], "uniprot_id": "Q9Y4L1" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "medium", "disease": "extrahepatic cholangiocarcinoma (eCCA)", "glycan_involvement": "High-mannose N-glycosylation at N641.", "mechanism": "Mannose-rich glycoforms of STT3B correlate with immune cell infiltration.", "protein": "STT3B", "protein_enriched": { "function": "May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Binds preferentially to methylated DNA (PubMed:28473536)", "gene_name": "LHX4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q969G2" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "high", "disease": "immunosuppressive tumor microenvironment", "glycan_involvement": "Promotes mannose-type N-glycosylation on immune-modulatory proteins.", "mechanism": "DPM1 upregulation is linked to reduced NK/NKT/memory B cell infiltration.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "high", "disease": "tumor metastasis", "glycan_involvement": "Reduces mannose-rich glycoforms on adhesion proteins.", "mechanism": "DPM1 knockdown impairs cell migration, implicating N-glycosylation in metastatic potential.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12615305" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "LDLR glycosylation supports cell surface localization and ligand binding.", "mechanism": "LDLR mediates SARS-CoV-2 entry via ApoE bridging; blocking LDLR inhibits infection.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "LDLR glycosylation required for proper folding and surface expression.", "mechanism": "LDLR binds ApoE on HBV envelope, facilitating viral entry; anti-LDLR antibody blocks infection.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Pseudorabies", "glycan_involvement": "LDLR glycosylation enables PRV gE interaction.", "mechanism": "LDLR co-localizes with PRV gE glycoprotein for entry; knockdown reduces infection.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "LDLR glycosylation supports viral glycoprotein binding.", "mechanism": "LDLR interacts with JEV envelope gE for cell entry; knockout or ligand competition inhibits infection.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Crimean-Congo hemorrhagic fever", "glycan_involvement": "LDLR glycosylation required for Gc interaction.", "mechanism": "LDLR binds CCHFV Gc glycoprotein for entry; deficiency delays disease.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "LDLR glycosylation required for cholesterol uptake.", "mechanism": "RSV activates SREBP2-LDLR axis to promote cholesterol uptake and replication; knockout inhibits infection.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "LDLR glycosylation supports lipoprotein binding.", "mechanism": "LDLR mediates cholesterol uptake, supporting HCV replication and entry; upregulated by HCV.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Alphavirus encephalitis (SFV, EEEV)", "glycan_involvement": "VLDLR glycosylation required for ligand-binding domain function.", "mechanism": "VLDLR binds alphavirus E2-E1 glycoproteins for cell entry; mutations alter susceptibility.", "protein": "VLDLR", "protein_enriched": { "function": "Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Also binds to a wide range of other molecu", "gene_name": "VLDLR", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G28541PG", "G43417UB", "G57321FI", "G82501QM" ], "uniprot_id": "P98155" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12615471" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "LRP1 glycosylation supports cholesterol transport.", "mechanism": "LRP1 reduces intracellular cholesterol and inhibits DENV replication; DENV downregulates LRP1 to promote infection.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC12615471" }, { "confidence": "medium", "disease": "Human cytomegalovirus infection", "glycan_involvement": "LRP1 glycosylation required for function.", "mechanism": "LRP1 expression increases during HCMV infection, reducing viral cholesterol and infectivity.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC12615471" }, { "confidence": "high", "disease": "Pemphigus vulgaris", "glycan_involvement": "Desmoglein-3 is a glycoprotein; glycosylation may affect antibody binding and pathogenicity.", "mechanism": "IgG autoantibodies target desmoglein-3, disrupting keratinocyte adhesion and causing blistering.", "protein": "Desmoglein-3", "protein_enriched": { "function": "Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and ", "gene_name": "GGA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UJY5" }, "relationship_type": "causal", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "Pemphigus vulgaris", "glycan_involvement": "FcRn is glycosylated; glycosylation may modulate IgG recycling and antibody pathogenicity.", "mechanism": "FcRn binding is necessary for pathogenicity of anti-desmoglein-3 antibodies in keratinocytes.", "protein": "FcRn (Neonatal Fc receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Complement proteins are glycosylated; glycan modifications affect activation and cell binding.", "mechanism": "Elevated CB-CAPs on blood cells indicate complement activation and correlate with microvascular APS and thrombosis risk.", "protein": "Cell-bound complement activation products (CB-CAPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12615490" }, { "confidence": "medium", "disease": "Psoriatic arthritis (PsA)", "glycan_involvement": "APOF is a glycoprotein; glycosylation may influence plasma stability and immune interactions.", "mechanism": "APOF levels are positively associated with PsA risk; genetic colocalization supports causal role.", "protein": "Apolipoprotein F (APOF)", "protein_enriched": { "function": "Minor apolipoprotein that associates with LDL. Inhibits cholesteryl ester transfer protein (CETP) activity and appears to be an important regulator of cholesterol transport. Also associates to a lesse", "gene_name": "APOF", "glycan_count": 33, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G08918WF", "G10486CT", "G11629QQ", "G15169WU", "G20312EM", "G22310AV", "G25541YH", "G39595FH", "G40574BA", "G45395BF", "G48414YA", "G55412XP", "G56784JY", "G59626AS", "G64394MX", "G70232NH", "G81263BG", "G86500WE", "G95865ZB", "G06247RL", "G11911BT", "G43089EG", "G55132BD", "G75983OB", "G57321FI", "G52527GH", "G29931IJ", "G43417UB", "G27391WQ", "G29068FM", "G53434XO", "G58001LT" ], "uniprot_id": "Q13790" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615490" }, { "confidence": "medium", "disease": "Psoriatic arthritis (PsA)", "glycan_involvement": "IL-10 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Higher IL-10 levels are inversely associated with PsA risk, suggesting anti-inflammatory protection.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12615490" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "SREBPs are glycoproteins; glycosylation may affect stability and transcriptional activity.", "mechanism": "SREBPs regulate lipid metabolism and cytokine production, contributing to immune activation and tissue damage.", "protein": "Sterol regulatory element-binding proteins (SREBPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgE is heavily glycosylated; glycan structure affects effector functions and immune complex formation.", "mechanism": "IgE anti-nuclear antibodies correlate with disease activity and organ involvement in SLE and other CTDs.", "protein": "IgE autoantibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "ACPAs are glycoproteins; glycosylation influences antigen recognition and immune activation.", "mechanism": "ACPAs are produced in response to microbial dysbiosis and are a hallmark of RA.", "protein": "Anti-citrullinated protein antibodies (ACPAs)", "relationship_type": "biomarker", "source_pmcid": "PMC12615490" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Mina53 is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Elevated Mina53 serum levels and gene expression correlate with SLE severity.", "protein": "Mina53", "protein_enriched": { "function": "Regulator of the tubulin polyglutamylase complex (TPGC) that controls cytoskeletal organization, nuclear shape, and cilium disassembly by balancing microtubule and actin assembly (PubMed:34782749). Re", "gene_name": "CSTPP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6J7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "Pemphigus vulgaris", "glycan_involvement": "Desmoglein-1 is glycosylated; glycan structures may modulate antibody binding.", "mechanism": "IgG autoantibodies target desmoglein-1, contributing to loss of keratinocyte adhesion.", "protein": "Desmoglein-1", "relationship_type": "causal", "source_pmcid": "PMC12615490" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates immune evasion.", "mechanism": "S glycoprotein mediates viral entry by binding to host cell receptors and is a key antigen for immune recognition.", "protein": "S glycoprotein (SARS-CoV-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "No direct glycosylation reported; not a glycoprotein.", "mechanism": "MPT64 is secreted by actively dividing M. tuberculosis and is immunodominant, used for TB diagnosis.", "protein": "MPT64", "protein_enriched": { "function": "Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to bind both H(2)PO", "gene_name": "pstS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P9WGU1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615495" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "N-glycosylation modulates immune recognition and viral infectivity.", "mechanism": "S glycoprotein mediates viral entry and is a target for immune detection.", "protein": "MERS-CoV S glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12615495" }, { "confidence": "medium", "disease": "Mpox (Monkeypox)", "glycan_involvement": "Binds host glycans; not itself a glycoprotein.", "mechanism": "A29 protein interacts with host glycosaminoglycans for cell entry; potential diagnostic marker.", "protein": "MPXV A29 protein", "relationship_type": "biomarker", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and antibody accessibility.", "mechanism": "Targeted by vaccines and neutralizing antibodies due to its role in viral entry.", "protein": "S glycoprotein (SARS-CoV-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans modulate receptor binding and immune evasion.", "mechanism": "Essential for viral attachment, fusion, and entry into host cells.", "protein": "S glycoprotein (SARS-CoV-2)", "relationship_type": "causal", "source_pmcid": "PMC12615495" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "No glycosylation involvement.", "mechanism": "Contributes to M. tuberculosis virulence and immune modulation.", "protein": "MPT64", "protein_enriched": { "function": "Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to bind both H(2)PO", "gene_name": "pstS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P9WGU1" }, "relationship_type": "causal", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "Used as a target antigen in sensitive biosensors for COVID-19 detection.", "protein": "S glycoprotein (SARS-CoV-2)", "relationship_type": "diagnostic", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Used as a target antigen in biosensors for rapid TB detection.", "protein": "MPT64", "protein_enriched": { "function": "Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to bind both H(2)PO", "gene_name": "pstS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P9WGU1" }, "relationship_type": "diagnostic", "source_pmcid": "PMC12615495" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "N-glycosylation influences immune recognition.", "mechanism": "Targeted by neutralizing antibodies and vaccines.", "protein": "MERS-CoV S glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12615495" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects AGP's half-life and immunomodulatory function.", "mechanism": "AGP is elevated during systemic inflammation and used to adjust ferritin as an iron status marker.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation modulates CRP's solubility and function.", "mechanism": "CRP is increased in systemic inflammation and used to adjust iron status biomarkers.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "Glycosylation is required for sTfR stability and serum detection.", "mechanism": "sTfR is elevated in iron deficiency due to increased erythropoiesis.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "Ferritin is glycosylated, affecting its serum stability.", "mechanism": "Low ferritin indicates depleted iron stores; used to diagnose iron deficiency.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation may modulate ferritin's clearance during inflammation.", "mechanism": "Ferritin is an acute phase reactant and can be elevated in inflammation, confounding iron deficiency diagnosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "N-glycosylation is essential for transferrin's iron-binding and receptor interaction.", "mechanism": "Transferrin saturation decreases in iron deficiency.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Altered glycosylation patterns in AGP are associated with HIV progression.", "mechanism": "AGP is elevated in children with HIV, reflecting chronic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation is necessary for sTfR's function and detection.", "mechanism": "sTfR is higher in children with HIV, indicating increased erythropoietic drive and iron demand.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "medium", "disease": "Gut mucosal damage", "glycan_involvement": "Glycosylation may affect IFABP's stability and release.", "mechanism": "Elevated IFABP indicates enterocyte damage, which is more common in children with HIV.", "protein": "Intestinal fatty acid binding protein (IFABP)", "protein_enriched": { "function": "FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds satura", "gene_name": "FABP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12104" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Anaemia", "glycan_involvement": "Glycosylation affects ferritin's serum half-life.", "mechanism": "Low ferritin is associated with iron-deficiency anaemia.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12615833" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus Infection (HIV)", "glycan_involvement": "N-glycosylation shields gp120 from immune recognition and affects receptor binding", "mechanism": "gp120 mediates viral entry by binding to CD4 and CCR5/CXCR4 on host cells", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus Infection (HIV)", "glycan_involvement": "N-glycosylation modulates fusion activity and immune evasion", "mechanism": "gp41 facilitates fusion of viral and host membranes after gp120 binding", "protein": "HIV Envelope Glycoprotein gp41", "relationship_type": "causal", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus Infection (HIV)", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity", "mechanism": "p24 antigen is detected in blood during early HIV infection", "protein": "HIV p24 Antigen", "protein_enriched": { "function": "Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruit", "gene_name": "gag-pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12497" }, "relationship_type": "biomarker", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus Infection (HIV)", "glycan_involvement": "O-glycosylation modulates receptor function and HIV binding", "mechanism": "CCR5 acts as a co-receptor for HIV entry; antagonists block infection", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus Infection (HIV)", "glycan_involvement": "N-glycosylation influences gp120 binding affinity", "mechanism": "CD4 is the primary receptor for HIV gp120 binding and entry", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12616222" }, { "confidence": "medium", "disease": "Drug-resistant HIV Infection", "glycan_involvement": "Glycosylation may affect drug binding and resistance", "mechanism": "Reverse transcriptase is targeted by NRTIs/NNRTIs; mutations confer resistance", "protein": "HIV Reverse Transcriptase", "protein_enriched": { "function": "Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruit", "gene_name": "gag-pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04585" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12616222" }, { "confidence": "medium", "disease": "Drug-resistant HIV Infection", "glycan_involvement": "Glycosylation can modulate enzyme activity and inhibitor binding", "mechanism": "Protease inhibitors block viral maturation; mutations confer resistance", "protein": "HIV Protease", "protein_enriched": { "function": "Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruit", "gene_name": "gag-pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03366" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12616222" }, { "confidence": "medium", "disease": "Drug-resistant HIV Infection", "glycan_involvement": "Glycosylation may affect enzyme stability and drug interaction", "mechanism": "Integrase inhibitors prevent viral DNA integration; resistance mutations reduce efficacy", "protein": "HIV Integrase", "protein_enriched": { "function": "The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Requir", "gene_name": "MAPK8IP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQF2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Perinatal HIV Transmission", "glycan_involvement": "Glycan shield affects transmission efficiency and immune evasion", "mechanism": "gp120 mediates transmission from mother to child via placental or breastfeeding routes", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Acute Retroviral Syndrome", "glycan_involvement": "Glycosylation impacts antigen detection and immune response", "mechanism": "gp120 and p24 antigens are detectable during acute infection phase", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "biomarker", "source_pmcid": "PMC12616222" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "PLN is a glycoprotein; glycosylation may affect stability and localization, but phosphorylation is the main regulatory PTM here.", "mechanism": "Dephosphorylated PLN inhibits SERCA2a, reducing Ca2+ uptake and contractility in failing hearts.", "protein": "Phospholamban (PLN)", "protein_enriched": { "function": "Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+) (PubMed:28890335). Binds preferentially to the ATP-boun", "gene_name": "PLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P26678" }, "relationship_type": "causal", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "SERCA2a is glycosylated; glycosylation may affect folding and membrane localization.", "mechanism": "Reduced SERCA2a activity impairs Ca2+ cycling; restoring activity improves contractility.", "protein": "SERCA2a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "No direct glycosylation role described for I-1 in this context.", "mechanism": "Constitutively active I-1 inhibits PP1, increasing PLN phosphorylation and SERCA2a activity, improving cardiac function.", "protein": "PP1 inhibitor 1 (I-1)", "protein_enriched": { "function": "Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketogluta", "gene_name": "GLS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UI32" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "PP1 may be glycosylated; glycosylation could affect enzyme activity, but not discussed here.", "mechanism": "Increased PP1 activity in failing hearts leads to PLN dephosphorylation and reduced SERCA2a activity.", "protein": "Protein phosphatase 1 (PP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12618250" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation may modulate PLN function, but phosphorylation is primary.", "mechanism": "PLN dysregulation contributes to hypertrophy via impaired Ca2+ handling.", "protein": "Phospholamban (PLN)", "protein_enriched": { "function": "Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+) (PubMed:28890335). Binds preferentially to the ATP-boun", "gene_name": "PLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P26678" }, "relationship_type": "causal", "source_pmcid": "PMC12618250" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation not directly implicated.", "mechanism": "PLN dysregulation leads to adverse remodeling and fibrosis.", "protein": "Phospholamban (PLN)", "protein_enriched": { "function": "Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+) (PubMed:28890335). Binds preferentially to the ATP-boun", "gene_name": "PLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P26678" }, "relationship_type": "causal", "source_pmcid": "PMC12618250" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "No direct glycosylation role described.", "mechanism": "I-1c expression maintains PLN phosphorylation, reducing arrhythmogenic risk.", "protein": "PP1 inhibitor 1 (I-1)", "protein_enriched": { "function": "Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketogluta", "gene_name": "GLS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UI32" }, "relationship_type": "protective", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation affects stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Acute cardiac failure", "glycan_involvement": "Troponin I is glycosylated; glycosylation may affect detection and stability.", "mechanism": "Troponin I elevation indicates myocardial injury.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12618250" }, { "confidence": "medium", "disease": "COVID-19 infection", "glycan_involvement": "C3 is heavily glycosylated; glycosylation is essential for function and immune recognition.", "mechanism": "Complement activation is associated with inflammation in infection and cardiovascular events.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618250" }, { "confidence": "high", "disease": "Transfusion-related immune modulation (TRIM)", "glycan_involvement": "PSGL-1 glycosylation is essential for P-selectin binding.", "mechanism": "P-selectin on platelets binds PSGL-1 on monocytes, forming adhesion synapses that modulate immune responses.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12618928" }, { "confidence": "high", "disease": "Transfusion-related immune modulation (TRIM)", "glycan_involvement": "O-glycosylation required for P-selectin binding.", "mechanism": "Glycosylated PSGL-1 interacts with P-selectin, facilitating monocyte-to-DC differentiation and immune modulation.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Viral infection", "glycan_involvement": "CD83 is a glycoprotein; glycosylation may affect stability and surface expression.", "mechanism": "Reduced CD83 expression on mDCs after platelet transfusion impairs DC maturation and antiviral T cell activation.", "protein": "CD83", "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Platelet transfusion-induced inflammation", "glycan_involvement": "CD40L is glycosylated; glycosylation may modulate receptor binding.", "mechanism": "Stored platelets express CD40L, triggering proinflammatory pathways in leukocytes.", "protein": "CD40L (CD154)", "protein_enriched": { "function": "Cytokine that acts as a ligand to CD40/TNFRSF5 (PubMed:1280226, PubMed:31331973). Costimulates T-cell proliferation and cytokine production (PubMed:8617933). Its cross-linking on T-cells generates a c", "gene_name": "CD40LG", "glycan_count": 33, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02763QD", "G08146BT", "G22140GZ", "G27310MQ", "G36191CD", "G37868ZX", "G39213VZ", "G42358LZ", "G45495MK", "G51369CD", "G51623PN", "G53276NK", "G55220VL", "G56903ZB", "G57818FI", "G61894MD", "G64411TU", "G67971GL", "G71269BI", "G78059CC", "G80858MF", "G86750HK", "G88068QT", "G92188CK", "G06110VR", "G06356OH", "G22310AV", "G23863VK", "G48414YA", "G49874UX", "G50045TK", "G70101JE", "G84452RH" ], "uniprot_id": "P29965" }, "relationship_type": "causal", "source_pmcid": "PMC12618928" }, { "confidence": "high", "disease": "Immunotolerance", "glycan_involvement": "TGF-\u03b21 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Platelet-derived TGF-\u03b21 induces tolerogenic DCs and promotes Treg differentiation.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Immunotolerance", "glycan_involvement": "CD80 glycosylation may influence cell surface expression.", "mechanism": "TGF-\u03b21-modified DCs show reduced CD80 expression, promoting tolerance.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Immunotolerance", "glycan_involvement": "CD86 glycosylation may influence cell surface expression.", "mechanism": "TGF-\u03b21-modified DCs show reduced CD86 expression, promoting tolerance.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Platelet transfusion-induced inflammation", "glycan_involvement": "MCP-1 is glycosylated; glycosylation may affect chemokine activity.", "mechanism": "Apheresis platelets increase MCP-1 production, enhancing leukocyte recruitment and inflammation.", "protein": "MCP-1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Platelet transfusion-induced inflammation", "glycan_involvement": "IL-8 is glycosylated; glycosylation may affect chemokine activity.", "mechanism": "Apheresis platelets increase IL-8 production, promoting neutrophil recruitment and inflammation.", "protein": "IL-8 (CXCL8)", "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "medium", "disease": "Viral infection", "glycan_involvement": "IP-10 is glycosylated; glycosylation may affect chemokine activity.", "mechanism": "Platelet transfusion inhibits IP-10 production during viral infection, potentially modulating immune cell trafficking.", "protein": "IP-10 (CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC12618928" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ECM interactions and stability.", "mechanism": "Elevated in serum, reflects ECM remodeling and muscle regeneration.", "protein": "Thrombospondin-4", "protein_enriched": { "function": "", "gene_name": "SMCO4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRQ5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "O-glycosylation affects cell signaling and immune modulation.", "mechanism": "Decreased in serum, increased in muscle tissue; involved in inflammation and regeneration.", "protein": "Osteopontin (SPP1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation critical for complement activation and immune function.", "mechanism": "Significantly decreased in serum; increased mRNA in muscle, suggesting local complement activation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation modulates cell-cell adhesion properties.", "mechanism": "Decreased in serum; reflects ECM degradation and loss of cell adhesion.", "protein": "Cadherin-17", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH17", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22573RC", "G27058EU", "G39446WN", "G41071NU", "G08918WF", "G45395BF" ], "uniprot_id": "Q12864" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "O-glycosylation influences mineralization and ECM binding.", "mechanism": "Decreased in serum; associated with ECM integrity and muscle pathology.", "protein": "Bone sialoprotein 2 (IBSP)", "protein_enriched": { "function": "Binds tightly to hydroxyapatite (PubMed:11459848). Appears to form an integral part of the mineralized matrix (PubMed:1818768). Probably important to cell-matrix interaction (PubMed:1818768). Promotes", "gene_name": "IBSP", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P21815" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Predicted N-glycosylation may regulate secretion and ECM interactions.", "mechanism": "Elevated in serum; involved in cell adhesion and ECM signaling.", "protein": "Coiled-coil domain-containing protein 80 (CCDC80)", "protein_enriched": { "function": "May bind integrin alpha-8/beta-1 and play a role in hair follicle morphogenesis. Promotes matrix assembly (By similarity)", "gene_name": "EGFL6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G71142DF" ], "uniprot_id": "Q8IUX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation affects IGF binding and bioavailability.", "mechanism": "Elevated in serum; modulates IGF signaling and muscle regeneration.", "protein": "Insulin-like growth factor binding protein 2 (IGFBP2)", "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may influence secretion and anti-inflammatory activity.", "mechanism": "Elevated in serum; regulates inflammation and muscle repair.", "protein": "Annexin A1 (ANXA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation modulates cytokine stability and receptor binding.", "mechanism": "Decreased in serum; involved in immune response and inflammation.", "protein": "Interleukin-36 alpha (IL36A)", "protein_enriched": { "function": "Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the ", "gene_name": "IL36A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UHA7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation affects cell surface localization and enzymatic activity.", "mechanism": "Decreased in serum and muscle; may regulate cell signaling and immune modulation.", "protein": "Ecto-ADP-ribosyltransferase 3 (ART3)", "protein_enriched": { "function": "", "gene_name": "ART3", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08290VR", "G25451PN", "G34989PA", "G36379GD", "G45395BF", "G47012YE", "G92275SC", "G29931IJ", "G43417UB" ], "uniprot_id": "Q13508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618936" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycosylated dystroglycan to tether ECM to cytoskeleton.", "mechanism": "Loss of dystrophin disrupts DGC assembly, leading to muscle fragility and impaired muscle stem cell polarity.", "protein": "Dystrophin (DMD)", "relationship_type": "causal", "source_pmcid": "PMC12618940" }, { "confidence": "high", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation of dystroglycan is essential for ECM binding.", "mechanism": "Dystroglycan glycosylation is required for DGC function; loss of dystrophin impairs DAG1 localization and function.", "protein": "Dystroglycan (DAG1)", "relationship_type": "causal", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylated utrophin interacts with ECM and DGC components.", "mechanism": "Utrophin partially compensates for dystrophin loss at the basal lamina during early development.", "protein": "Utrophin (UTRN)", "relationship_type": "protective", "source_pmcid": "PMC12618940" }, { "confidence": "high", "disease": "Muscle stem cell polarity dysfunction", "glycan_involvement": "Indirect; MARK2 function depends on DGC integrity.", "mechanism": "MARK2 interacts with dystrophin to establish MuSC polarity; loss of dystrophin downregulates MARK2.", "protein": "MARK2", "relationship_type": "causal", "source_pmcid": "PMC12618940" }, { "confidence": "high", "disease": "Muscle stem cell polarity dysfunction", "glycan_involvement": "Indirect; NUMB function is regulated by DGC-mediated polarity.", "mechanism": "NUMB polarization is reduced in dystrophin-deficient MuSCs, impairing asymmetric division and progenitor generation.", "protein": "NUMB", "protein_enriched": { "function": "Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to ", "gene_name": "NUMBL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R0" }, "relationship_type": "causal", "source_pmcid": "PMC12618940" }, { "confidence": "high", "disease": "Muscle stem cell polarity dysfunction", "glycan_involvement": "Indirect; AAK1 regulates NUMB, which is downstream of DGC.", "mechanism": "AAK1 deletion restores NUMB polarization and rescues myogenic progenitor generation in mdx fetal muscle.", "protein": "AAK1", "protein_enriched": { "function": "Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during t", "gene_name": "AAK1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q2M2I8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "Muscle fragility", "glycan_involvement": "COL4A1 glycosylation is important for ECM structure.", "mechanism": "Reduced COL4A1 staining in mdx muscle reflects ECM disruption due to DGC dysfunction.", "protein": "COL4A1", "relationship_type": "biomarker", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "Muscle fragility", "glycan_involvement": "Laminin glycosylation is required for ECM integrity.", "mechanism": "Reduced laminin staining in mdx muscle indicates impaired ECM assembly.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "Muscle stem cell polarity dysfunction", "glycan_involvement": "Syndecan glycosylation modulates cell-matrix interactions.", "mechanism": "Syndecan expression is altered in fMuSCs, reflecting changes in cell adhesion and polarity.", "protein": "Syndecan", "relationship_type": "biomarker", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "Muscle fragility", "glycan_involvement": "Fibronectin glycosylation affects ECM binding.", "mechanism": "Fibronectin expression changes in mdx muscle indicate ECM remodeling.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12618940" }, { "confidence": "medium", "disease": "acute myocardial infarction", "glycan_involvement": "glycosylation required for ligand binding and cell trafficking", "mechanism": "p-selectin mediates leukocyte-endothelial adhesion, promoting inflammation in coronary arteries", "protein": "p-selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "medium", "disease": "acute severe cholecystitis", "glycan_involvement": "N-glycans modulate leukocyte binding", "mechanism": "ICAM-1 upregulated on endothelium during inflammation, facilitating neutrophil infiltration", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "medium", "disease": "sepsis", "glycan_involvement": "sialyl Lewis X glycan required for selectin-ligand interaction", "mechanism": "E-selectin expression increases during systemic inflammation, mediating leukocyte rolling", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "medium", "disease": "acute severe cholecystitis", "glycan_involvement": "glycosylation affects CRP stability and function", "mechanism": "CRP is an acute phase reactant elevated in severe infection", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "medium", "disease": "acute myocardial infarction", "glycan_involvement": "N-glycans modulate fibrinogen function and clot formation", "mechanism": "Fibrinogen increases during acute phase, contributing to thrombosis risk", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "medium", "disease": "acute myocardial infarction", "glycan_involvement": "glycosylation regulates vWF multimerization and activity", "mechanism": "vWF mediates platelet adhesion, elevated in vascular injury", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "low", "disease": "sepsis", "glycan_involvement": "altered glycosylation reflects inflammation", "mechanism": "Transferrin glycoforms change during acute phase response", "protein": "transferrin", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "low", "disease": "acute severe cholecystitis", "glycan_involvement": "Fc N-glycosylation affects effector function", "mechanism": "IgG glycoforms modulate immune response in infection", "protein": "immunoglobulin G (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "low", "disease": "pericholecystic abscess", "glycan_involvement": "glycosylation modulates enzyme activity", "mechanism": "Neutrophil elastase released during abscess formation, contributing to tissue damage", "protein": "neutrophil elastase", "relationship_type": "causal", "source_pmcid": "PMC12619526" }, { "confidence": "low", "disease": "acute severe cholecystitis", "glycan_involvement": "glycosylation affects serum half-life", "mechanism": "AST released from damaged hepatocytes during severe inflammation", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12619526" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Glycosylation required for secretion and enzymatic activity, facilitating ECM interactions.", "mechanism": "Promotes ECM remodeling and activates MAPK/ERK and Wnt/\u03b2-catenin signaling, enhancing proliferation and invasion; high expression correlates with poor prognosis.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation supports secretion and function in ECM remodeling.", "mechanism": "Enhances EMT, proliferation, migration, and invasion via stabilization of BCL-2 and interaction with CEBPA/Tip60; high expression predicts poor prognosis.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N- and O-glycosylation necessary for secretion and catalytic activity.", "mechanism": "Promotes invasion, EMT, and chemoresistance by stabilizing DHODH and inhibiting mitochondrial ferroptosis; upregulated by TGF-\u03b21.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation required for secretion and ECM remodeling.", "mechanism": "Drives invasion, metastasis, and angiogenesis; knockdown induces ferroptosis; regulated by TGF-\u03b2 signaling.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation supports ECM remodeling and metastatic phenotype.", "mechanism": "High expression correlates with EMT, metastasis, and poor prognosis; interacts with ZEB2 and miR-34a axis.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619944" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation required for ECM remodeling and immune modulation.", "mechanism": "Regulates EMT via SNAIL interaction, promotes fibrosis and immunosuppressive microenvironment; ATO modulates LOXL3 to enhance immunotherapy.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for secretion and ECM remodeling.", "mechanism": "Promotes proliferation, invasion, and metastasis via SNAIL-mediated EMT and collagen fiber alignment; expression correlates with inflammatory response and hormone receptor status.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619944" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation supports secretion and ECM interaction.", "mechanism": "High plasma LOXL3 predicts poor prognosis and chemoresistance, possibly via integrin signaling and ECM-cell interaction.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation required for secretion and ECM remodeling.", "mechanism": "Promotes EMT and metastasis via SNAIL1/PRRX1 axis and BRAF signaling; high expression predicts poor prognosis.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation required for functional secretion and ECM remodeling.", "mechanism": "LOXL3 knockdown induces ferroptosis, inhibiting proliferation and metastasis; effect reversed by ferroptosis inhibitor Fer-1.", "protein": "LOXL3", "protein_enriched": { "function": "Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomeriz", "gene_name": "AZI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6S1" }, "relationship_type": "causal", "source_pmcid": "PMC12619944" }, { "confidence": "high", "disease": "IIM-ILD", "glycan_involvement": "Six IgG2 N-glycopeptides (e.g., increased IgG2-N4H3F1, decreased IgG2-N4H4F1) are significantly altered.", "mechanism": "Altered IgG2 N-glycosylation distinguishes IIM-ILD from IIM without ILD.", "protein": "IgG2", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "high", "disease": "cNSIP", "glycan_involvement": "Elevated IgG2-N4H5F1A1 and IgG2-N4H4F1; associated with less inflammation and shorter disease duration.", "mechanism": "Highly sialylated and galactosylated IgG2 glycoforms enriched in cNSIP subtype.", "protein": "IgG2", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "high", "disease": "fNSIP", "glycan_involvement": "Increased IgG1-N4H4F1; linked to longer disease duration and fibrotic phenotype.", "mechanism": "Elevated IgG1 glycoforms are characteristic of fNSIP subtype.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "fNSIP", "glycan_involvement": "Increased IgG3-N4H3F1; associated with impaired pulmonary function (lower DLCO%).", "mechanism": "Elevated IgG3 glycoforms in fNSIP subtype.", "protein": "IgG3", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "high", "disease": "OP", "glycan_involvement": "IgG2-N5H4F1 correlates with anti-MDA5 positivity and lower CK/LDH.", "mechanism": "Unique elevation of IgG2-N5H4F1 in OP subtype.", "protein": "IgG2", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "IIM-ILD", "glycan_involvement": "Lower total sialylation and galactosylation in IgG2 drive Fc\u03b3R activation and complement activation.", "mechanism": "Reduced sialylation and galactosylation promote inflammatory IgG phenotype.", "protein": "IgG2", "relationship_type": "causal", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "cNSIP", "glycan_involvement": "Higher IgG2-N4H5F1A1 and IgG2-N4H4F1 negatively correlate with CRP and disease duration.", "mechanism": "Sialylated/galactosylated IgG2 glycoforms may limit immune activation.", "protein": "IgG2", "relationship_type": "protective", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "fNSIP", "glycan_involvement": "IgG2-N4H3F1 positively correlates with CRP, LDH, muscle weakness.", "mechanism": "Agalactosylated IgG2 glycoforms (IgG2-N4H3F1) correlate with muscle weakness and inflammation.", "protein": "IgG2", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "OP", "glycan_involvement": "Elevated IgG2-N5H4F1 in OP subtype; associated with autoantibody and infection markers.", "mechanism": "IgG2-N5H4F1 correlates with anti-MDA5 positivity and infection.", "protein": "IgG2", "relationship_type": "biomarker", "source_pmcid": "PMC12620462" }, { "confidence": "medium", "disease": "IIM-ILD", "glycan_involvement": "IgG3-N4H3F1 inversely correlates with DLCO%.", "mechanism": "Agalactosylated IgG3 glycoforms linked to reduced lung diffusing capacity.", "protein": "IgG3", "relationship_type": "causal", "source_pmcid": "PMC12620462" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "MOG is a target antigen in MS and EAE, used to induce demyelination and neuroinflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation modulates MOG immunogenicity.", "mechanism": "MOG immunization induces EAE, modeling MS-like demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "NF-L is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "NF-L levels in plasma reflect axonal damage and neurodegeneration.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may influence NF-L release and detection.", "mechanism": "Elevated NF-L in plasma indicates axonal injury in EAE.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation may affect NF-L turnover and immunoassay performance.", "mechanism": "Increased plasma NF-L is a marker of axonal degeneration in ALS models.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "No direct glycosylation reported; included due to disease relevance.", "mechanism": "TDP43 aggregation is a hallmark of ALS pathology.", "protein": "Transactive response DNA binding protein 43 (TDP43)", "protein_enriched": { "function": "RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predomina", "gene_name": "Tardbp", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q921F2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "TDP43 aggregation is central to FTD neurodegeneration.", "protein": "Transactive response DNA binding protein 43 (TDP43)", "protein_enriched": { "function": "RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predomina", "gene_name": "Tardbp", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q921F2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "TDP43 pathology is observed in a subset of AD cases.", "protein": "Transactive response DNA binding protein 43 (TDP43)", "protein_enriched": { "function": "RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predomina", "gene_name": "Tardbp", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q921F2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12620470" }, { "confidence": "medium", "disease": "Cuprizone-induced demyelination", "glycan_involvement": "Glycosylation may affect MOG stability and immune response.", "mechanism": "MOG loss reflects demyelination in the cuprizone model.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "medium", "disease": "Cuprizone-induced demyelination", "glycan_involvement": "Glycosylation may affect NF-L detection.", "mechanism": "NF-L may increase with axonal injury in demyelination models.", "protein": "Neurofilament light chain", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal interm", "gene_name": "NEFL", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12620470" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Catalyzes \u03b12,6-sialylation of glycoproteins, including PD-L1.", "mechanism": "Promotes CRC cell proliferation, migration, invasion, and metastasis.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Upregulates \u03b12,6-sialylation; associated with reduced CD8+ T cell infiltration.", "mechanism": "High expression predicts poor prognosis and immunosuppressive TME.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation and \u03b12,6-sialylation maintain PD-L1 stability.", "mechanism": "Immune checkpoint; stability and function regulated by glycosylation.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Immunotherapy resistance in CRC", "glycan_involvement": "\u03b12,6-sialylation of PD-L1 prevents its ubiquitination and degradation.", "mechanism": "ST6GAL1-mediated sialylation stabilizes PD-L1, promoting immune evasion and resistance to anti-PD-L1 therapy.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Reduces \u03b12,6-sialylation of PD-L1, leading to its degradation.", "mechanism": "Knockdown enhances anti-PD-L1 therapy efficacy and increases CD8+ T cell infiltration.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "N-glycosylation and terminal \u03b12,6-sialylation are required for PD-L1 stability and immune suppression.", "mechanism": "Glycosylated PD-L1 interacts with PD-1, suppressing T cell function.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12622430" }, { "confidence": "medium", "disease": "Metastatic colorectal cancer (mCRC)", "glycan_involvement": "\u03b12,6-sialylation of cell surface glycoproteins.", "mechanism": "Promotes liver metastasis in mouse models.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12622430" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Associated with glycolytic pathway activity and immune cell composition.", "mechanism": "Stratifies CRC patients into metabolic and immune subgroups.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12622430" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "High ST6GAL1 expression correlates with EGFR pathway activation.", "mechanism": "Potential target to sensitize CRC to anti-EGFR therapy (cetuximab) via EGFR pathway modulation.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12622430" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation status (especially \u03b12,6-sialylation) affects PD-L1 detection and function.", "mechanism": "Co-localization with ST6GAL1 predicts immunosuppressive TME and poor prognosis.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12622430" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Altered N-glycosylation and Fc glycosylation patterns in AIH plasma.", "mechanism": "Elevated serum IgG is characteristic of AIH and used in diagnosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Potential glycosylation affects stability and clearance.", "mechanism": "Serum and urinary L-FABP levels correlate with liver injury markers (AST, ALT, GGT) in AIH.", "protein": "Liver fatty acid binding protein (L-FABP)", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Includes glycosylated immunoglobulins.", "mechanism": "Elevated gamma globulin levels are a diagnostic feature of AIH.", "protein": "Gamma globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Presence of ANA is used to classify and diagnose Type 1 AIH.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "ASMA positivity is characteristic of Type 1 AIH.", "protein": "Anti-smooth muscle antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Glycosylation may influence autoantibody specificity.", "mechanism": "Anti-LKM-1 is used to diagnose Type 2 AIH.", "protein": "Anti-liver/kidney microsome 1 (anti-LKM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Glycosylation may affect antigen presentation.", "mechanism": "Anti-LC-1 positivity is diagnostic for Type 2 AIH.", "protein": "Anti-liver cytosol type 1 (anti-LC-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect carrier protein function.", "mechanism": "Reduced serum retinyl ester is linked to hepatic stellate cell activation and early fibrosis.", "protein": "Retinyl ester carrier proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Altered N-glycosylation impacts glycoprotein function and clearance.", "mechanism": "High sialylation per galactose ratio on tetraantennary glycans is a specific plasma marker for AIH.", "protein": "Glycoproteins with tetraantennary N-glycans", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Fc N-glycosylation modulates immune effector functions.", "mechanism": "Distinct IgG Fc glycosylation patterns differentiate AIH from healthy controls.", "protein": "IgG Fc region", "relationship_type": "biomarker", "source_pmcid": "PMC12623311" }, { "confidence": "high", "disease": "Diabetic microvascular complications", "glycan_involvement": "Composite N-acetyl glycan signals from acute-phase glycoproteins.", "mechanism": "Reflects chronic inflammation linked to UPF intake and increased risk of complications.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "high", "disease": "Diabetic kidney disease", "glycan_involvement": "N-acetyl glycan moieties on acute-phase proteins.", "mechanism": "Elevated GlycA mediates association between UPF intake and kidney disease via inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic microvascular complications", "glycan_involvement": "N-glycosylation affects stability and function.", "mechanism": "Lower albumin levels mediate risk; reflects nutritional status and liver function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "N-glycosylation modulates albumin half-life.", "mechanism": "Decreased albumin associated with increased risk, possibly due to poor nutrition and liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic microvascular complications", "glycan_involvement": "Glycosylation affects lipid binding and anti-inflammatory properties.", "mechanism": "Lower ApoA1 and HDL lipid fractions linked to higher risk; involved in cholesterol transport.", "protein": "Apolipoprotein A1", "relationship_type": "protective", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic microvascular complications", "glycan_involvement": "Glycosylation influences lipoprotein metabolism.", "mechanism": "Elevated ApoB-containing lipoproteins (VLDL, LDL) mediate risk via dyslipidemia.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "N-acetyl glycan signals from acute-phase proteins.", "mechanism": "Higher GlycA levels associated with increased risk, reflecting inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "N-acetyl glycan signals from acute-phase proteins.", "mechanism": "Elevated GlycA mediates risk via inflammatory pathways.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "Glycosylation modulates anti-inflammatory function.", "mechanism": "Higher HDL/ApoA1 levels linked to lower risk; involved in reverse cholesterol transport.", "protein": "Apolipoprotein A1", "relationship_type": "protective", "source_pmcid": "PMC12624094" }, { "confidence": "medium", "disease": "Diabetic microvascular complications", "glycan_involvement": "N-acetyl glycan modifications on acute-phase proteins.", "mechanism": "Mediates UPF intake effect on complications via chronic inflammation.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "causal", "source_pmcid": "PMC12624094" }, { "confidence": "high", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "Glycosylation not required for most autoantibody binding; one patient required N-glycosylation.", "mechanism": "Autoantibodies against CNTN1 disrupt axoglial junctions at the node of Ranvier, causing sensorimotor neuropathy and sensory ataxia.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "high", "disease": "Glomerulonephritis", "glycan_involvement": "Not dependent on glycosylation for most patients.", "mechanism": "Autoantibodies targeting Ig domains of CNTN1 are associated with glomerulonephritis, possibly via immune complex formation.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "Diabetes mellitus is exclusively observed in patients with autoantibodies targeting the FnIII domain of CNTN1.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624422" }, { "confidence": "medium", "disease": "Proteinuria", "glycan_involvement": "Not dependent on glycosylation for most patients.", "mechanism": "Proteinuria is frequently found in patients with Ig domain-targeting autoantibodies, suggesting renal involvement.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624422" }, { "confidence": "high", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "No direct glycan involvement for linear epitopes.", "mechanism": "Linear epitopes in Ig domains (detected by peptide microarray) are associated with more severe disease, including need for mechanical ventilation.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "medium", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Autoantibodies targeting FnIII domains are associated with chronic disease course and diabetes mellitus.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "high", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "Not dependent on glycosylation for most patients.", "mechanism": "Autoantibodies targeting Ig domains are associated with acute/subacute onset and higher risk of glomerulonephritis.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "medium", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Persistence of epitope-specific autoantibodies (especially linear Ig domain epitopes) may indicate ongoing disease activity or risk of relapse.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624422" }, { "confidence": "low", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "N-glycosylation required for autoantibody binding in one patient.", "mechanism": "Glycosylation-dependent autoantibody binding (rare) may be associated with susceptibility to broader paranodal autoimmunity (e.g., epitope spreading to Caspr1).", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12624422" }, { "confidence": "high", "disease": "Autoimmune nodopathy with anti-CNTN1 autoantibodies", "glycan_involvement": "Mostly independent of glycosylation.", "mechanism": "Epitope mapping (Ig vs FnIII domain) can predict comorbidities (glomerulonephritis, diabetes) and disease course (acute vs chronic).", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12624422" }, { "confidence": "high", "disease": "Gaucher disease", "glycan_involvement": "Glycosylation status may influence protein stability and detection as a biomarker.", "mechanism": "Acts as a biomarker of inflammation in individuals with Gaucher disease; levels correlate with clinico-pathological subtypes.", "protein": "Glycoprotein non-metastatic melanoma protein B", "relationship_type": "biomarker", "source_pmcid": "PMC12624977" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Fibrinogen is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Serum FIBA-derived peptides are significantly associated with 1-year all-cause mortality in HF; changes reflect complement and coagulation cascade activation.", "protein": "Fibrinogen alpha chain (FIBA)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may modulate peptide generation and function.", "mechanism": "FIBA-derived peptides may regulate ACE, neprilysin, and DPP-IV, influencing HF pathophysiology.", "protein": "Fibrinogen alpha chain (FIBA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12625115" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation impacts fibrinogen's interactions with cells and proteases.", "mechanism": "Fibrinogen mediates coagulation, inflammation, and vascular dysfunction, contributing to disease progression.", "protein": "Fibrinogen alpha chain (FIBA)", "relationship_type": "causal", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "FGB is glycosylated, affecting its plasma half-life and function.", "mechanism": "FGB levels are regulated by drugs to improve coagulation in coronary heart disease.", "protein": "Fibrinogen beta chain (FGB)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "FGG glycosylation influences its role in coagulation.", "mechanism": "FGG levels are modulated in therapy to improve coagulation.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "A2MG is highly glycosylated, which affects its protease inhibitor function.", "mechanism": "A2MG-derived peptides are differentially expressed in HF and may reflect protease activity.", "protein": "Alpha-2-macroglobulin (A2MG)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Thrombin is glycosylated, influencing its activity and interactions.", "mechanism": "THRB-derived peptides are altered in HF, reflecting coagulation cascade activation.", "protein": "Thrombin (THRB)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "PROC glycosylation affects activation and function.", "mechanism": "PROC-derived peptides are differentially expressed in HF, indicating altered coagulation.", "protein": "Prothrombin (PROC)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "APOE is glycosylated, which modulates receptor binding and clearance.", "mechanism": "APOE-derived peptides are altered in HF, possibly reflecting lipid metabolism changes.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "MMRN1 is a glycoprotein; glycosylation affects its multimerization and function.", "mechanism": "MMRN1-derived peptides are differentially expressed in HF, related to platelet activation.", "protein": "Multimerin-1 (MMRN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12625115" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation may affect aggregation and clearance.", "mechanism": "Reflects tau phosphorylation and aggregation associated with AD pathology; correlates with amyloid and tau PET status.", "protein": "p-tau217", "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may modulate stability and immune recognition.", "mechanism": "Astrocyte activation marker; elevated in AD plasma.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Frontotemporal dementia", "glycan_involvement": "NEFL is O-glycosylated; glycosylation affects filament assembly.", "mechanism": "Axonal injury marker; highest effect size in FTD among diseases.", "protein": "NEFL", "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies", "glycan_involvement": "MSLN is N-glycosylated; glycosylation impacts secretion and immune interactions.", "mechanism": "Specific plasma elevation in DLB; may reflect neuroinflammation.", "protein": "MSLN", "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies", "glycan_involvement": "SAA1 is glycosylated; glycosylation modulates solubility and clearance.", "mechanism": "Specific to DLB; acute phase protein linked to inflammation.", "protein": "SAA1", "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "FLT1 is N-glycosylated; glycosylation affects receptor signaling.", "mechanism": "Specific association with PD; involved in vascular/endothelial function.", "protein": "FLT1", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell sur", "gene_name": "FLT1", "glycan_count": 64, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G62765YT", "G00273SJ", "G01485JJ", "G08918WF", "G10846ZT", "G27058EU", "G27126ED", "G28622IK", "G34989PA", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G46691LC", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G76295SF", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G14669DU", "G28681TP", "G61256FT", "G80075MS", "G00912UN", "G04657PL", "G06356OH", "G10486CT", "G10488MI", "G10819WX", "G27947YN", "G28541PG", "G31852PQ", "G35029YA", "G37399XV", "G40926MX", "G45504EY", "G57776ZU", "G60033FS", "G65184UU", "G72787SB", "G72790NZ", "G77547TA", "G83633GK", "G86182NS", "G92551JA", "G95865ZB", "G40834TG", "G33609NS", "G39446WN", "G01650EU", "G02815KT", "G41247ZX", "G49151OV", "G23453IV", "G49108TO" ], "uniprot_id": "P17948" }, "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "PARK7 is glycosylated; glycosylation may affect stability.", "mechanism": "Elevated in PD; oxidative stress response protein.", "protein": "PARK7", "protein_enriched": { "function": "Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensi", "gene_name": "PARK7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99497" }, "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation required for cell surface expression.", "mechanism": "Microglial activation marker; enriched in AD protein-lipid binding pathway.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APOE is glycosylated; glycosylation modulates lipid binding and receptor interactions.", "mechanism": "Lipid transport and amyloid aggregation; enriched in AD protein-lipid binding pathway.", "protein": "APOE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SNCA is O-glycosylated; glycosylation affects aggregation propensity.", "mechanism": "Synucleinopathy marker; positive association with PD, negative with FTD.", "protein": "SNCA", "relationship_type": "biomarker", "source_pmcid": "PMC12625197" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation of HA affects antigenicity and immune recognition.", "mechanism": "HA is the primary antigenic target for neutralizing antibodies; its display on nanoparticles elicits protective immunity.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Incorporation of oligomannose-type N-glycan enhances immunogenicity and trafficking.", "mechanism": "Engineered nanoparticle displaying trimeric HA RBD induces potent neutralizing and receptor-blocking antibodies in mice.", "protein": "TH-I3-A7 (Trihead-I3-A7 nanoparticle)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Oligomannose-type N-glycan at N62 site modulates trafficking and immunogenicity.", "mechanism": "Glycosylated nanoparticle scaffold used for antigen display; glycan at N62 improves immunogen secretion and immune response.", "protein": "I3-A7cp-N62 (glycosylated variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation status not explicitly engineered but relevant for antigen display.", "mechanism": "Two-component nanoparticle displaying HA RBD induces robust antibody responses; benchmark for engineered scaffolds.", "protein": "I53_dn5 Nanoparticle", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Native glycosylation may affect immunogenicity and secretion.", "mechanism": "Natural self-assembling glycoprotein used as a scaffold for nanoparticle vaccines, including for influenza.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Native glycosylation may affect immunogenicity and secretion.", "mechanism": "Natural self-assembling glycoprotein used as a scaffold for nanoparticle vaccines.", "protein": "Lumazine Synthase", "protein_enriched": { "function": "Catalyzes the Claisen rearrangement of chorismate to prephenate and the decarboxylation/dehydration of prephenate to phenylpyruvate", "gene_name": "pheA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A9J8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "medium", "disease": "SARS-CoV-2 (COVID-19)", "glycan_involvement": "Glycosylation critical for antigen folding and immune response.", "mechanism": "Platform approach; similar nanoparticle vaccines licensed for SARS-CoV-2.", "protein": "TH-I3-A7 (Trihead-I3-A7 nanoparticle)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation required for secretion and immunogenicity.", "mechanism": "Engineered scaffold for antigen display; secretion from mammalian cells is glycan-dependent.", "protein": "I3-A7 Nanoparticle Scaffold", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Oligomannose-type glycan enhances immune engagement.", "mechanism": "Elicits receptor-blocking and neutralizing antibodies, conferring protection in mouse models.", "protein": "TH-I3-A7 (Trihead-I3-A7 nanoparticle)", "relationship_type": "protective", "source_pmcid": "PMC12626006" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Oligomannose-type glycan at N62 indicates early secretory pathway assembly.", "mechanism": "Glycan occupancy at N62 serves as a marker for nanoparticle assembly and trafficking.", "protein": "I3-A7cp-N62 (glycosylated variant)", "relationship_type": "biomarker", "source_pmcid": "PMC12626006" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "VEGF glycosylation is essential for secretion and receptor binding.", "mechanism": "VEGF promotes angiogenesis, supporting tumor growth and metastasis; inhibition reduces tumor vascularization.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626318" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "EGFR glycosylation modulates ligand binding and receptor activation.", "mechanism": "EGFR drives cell proliferation and survival in tumors; inhibition blocks oncogenic signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626318" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation of VEGF affects its stability and activity.", "mechanism": "VEGF-mediated angiogenesis is critical for glioblastoma progression; targeting VEGF impairs tumor blood supply.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626318" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "EGFR glycosylation influences receptor dimerization and signaling.", "mechanism": "EGFR overexpression and activation drive glioblastoma cell growth; inhibition suppresses tumor proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12626318" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Altered glycosylation may affect VEGF detection and function.", "mechanism": "Elevated VEGF levels correlate with tumor angiogenesis and poor prognosis.", "protein": "VEGF", "relationship_type": "biomarker", "source_pmcid": "PMC12626318" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation state can influence antibody recognition in diagnostics.", "mechanism": "EGFR expression and activation status serve as diagnostic and prognostic markers in cancer.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12626318" }, { 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"VEGF", "relationship_type": "causal", "source_pmcid": "PMC12626318" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Altered glycosylation may affect EGFR-mediated signaling in glioblastoma.", "mechanism": "EGFR mutations and overexpression contribute to glioblastoma aggressiveness.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", 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mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "medium", "disease": "Pachymeningitis", "glycan_involvement": "Glycosylation of MOG may influence immune recognition in meningeal tissues.", "mechanism": "MOG autoantibodies mediate rare pachymeningeal inflammation in MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, 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mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "high", "disease": "Myelitis", "glycan_involvement": "Glycosylation may affect MOG immune response in spinal cord.", "mechanism": "MOG autoantibodies cause spinal cord demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis", "glycan_involvement": "Glycosylation may influence MOG immunogenicity.", "mechanism": "MOG autoantibodies drive widespread CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "medium", "disease": "Brainstem encephalitis", "glycan_involvement": "Glycosylation may affect MOG antibody binding in brainstem.", "mechanism": "MOG autoantibodies mediate brainstem inflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "medium", "disease": "Cortical encephalitis", "glycan_involvement": "Glycosylation may modulate MOG antigen presentation in cortex.", "mechanism": "MOG autoantibodies cause cortical demyelination.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may influence MOG immune response in meninges.", "mechanism": "MOG autoantibodies induce non-infectious meningeal inflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12626688" }, { "confidence": "high", "disease": "Emphysematous hepatitis", "glycan_involvement": "Capsule polysaccharides are highly glycosylated, mediating virulence and resistance to phagocytosis.", "mechanism": "Capsular glycoproteins enable immune evasion and promote gas-forming infection in hepatic tissue.", "protein": "Klebsiella pneumoniae capsule polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12626690" }, { "confidence": "medium", "disease": "Emphysematous hepatitis", "glycan_involvement": "Glycosylation of toxins and surface proteins enhances pathogenicity.", "mechanism": "Bacterial glycoproteins contribute to tissue necrosis and gas production in liver.", "protein": "Clostridium perfringens glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12626690" }, { "confidence": "medium", "disease": "Emphysematous hepatitis", "glycan_involvement": "Surface glycoproteins mediate adhesion and immune evasion.", "mechanism": "E. coli glycoproteins facilitate infection and gas formation in hepatic parenchyma.", "protein": "Escherichia coli glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12626690" }, { "confidence": "medium", "disease": "Emphysematous hepatitis", "glycan_involvement": "Cell wall glycoproteins involved in host interaction.", "mechanism": "Glycoproteins contribute to infection and gas formation in liver tissue.", "protein": "Enterococcus faecalis glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12626690" }, { "confidence": "high", "disease": "Emphysematous hepatitis", "glycan_involvement": "AST is glycosylated, affecting stability and serum levels.", "mechanism": "Elevated AST indicates hepatic parenchymal injury due to infection.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). 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Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12626690" }, { "confidence": "high", "disease": "Emphysematous hepatitis", "glycan_involvement": "N-glycosylation affects ALP activity and secretion.", "mechanism": "ALP elevation is associated with biliary and hepatic injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12626690" }, { "confidence": "medium", "disease": "Emphysematous hepatitis", "glycan_involvement": "Fc glycosylation modulates effector function and pathogen clearance.", "mechanism": "IgG mediates immune response against bacterial pathogens.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12626690" }, { "confidence": "high", "disease": "Pyogenic liver abscess", "glycan_involvement": "Glycosylation critical for capsule integrity and virulence.", "mechanism": "Capsular glycoproteins promote abscess formation and resistance to host defenses.", "protein": "Klebsiella pneumoniae capsule polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC12626690" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Glycan structures on blood group antigens affect pathogen binding.", "mechanism": "Blood group glycoproteins may influence susceptibility to bacterial sepsis.", "protein": "Blood group antigens (general)", "relationship_type": "risk modifier", "source_pmcid": "PMC12626690" }, { "confidence": "high", "disease": "Cerebral infarction", "glycan_involvement": "HMGB1 is a glycoprotein; glycosylation may affect secretion and immune signaling.", "mechanism": "Quercetin reduces HMGB1 acetylation and secretion, inhibiting TLR4/MyD88/NF-\u03baB pathway, reducing neuroinflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Intracerebral hemorrhage", "glycan_involvement": "CD36 glycosylation modulates ligand binding and phagocytosis.", "mechanism": "Wogonin upregulates CD36, promoting microglial phagocytosis and hematoma clearance.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Intracerebral hemorrhage", "glycan_involvement": "LAMP2 is highly glycosylated; glycosylation is essential for lysosomal targeting.", "mechanism": "Wogonin increases LAMP2 expression, enhancing lysosomal function and hematoma clearance.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Cerebral infarction", "glycan_involvement": "BDNF glycosylation affects secretion and receptor interaction.", "mechanism": "Kaempferol upregulates BDNF-TrkB-PI3K/AKT signaling, reducing apoptosis and supporting neuroprotection.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "EGFR N-glycosylation regulates receptor stability and signaling.", "mechanism": "Baicalein modulates EGFR expression and degradation, inhibiting glioma cell proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation influences processing and A\u03b2 generation.", "mechanism": "Icariin promotes APP ubiquitination and proteasomal degradation, reducing A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "high", "disease": "Familial amyloidotic polyneuropathy", "glycan_involvement": "TTR is N-glycosylated; glycosylation may affect aggregation.", "mechanism": "EGCG reduces TTR deposition in peripheral nerves, decreasing amyloid burden.", "protein": "TTR", "relationship_type": "causal", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Myasthenia gravis", "glycan_involvement": "AChR glycosylation is critical for surface expression and autoantigenicity.", "mechanism": "Flavonoids inhibit acetylcholinesterase, increasing ACh at the neuromuscular junction, improving MG symptoms.", "protein": "AChR", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "SrtA acts on glycoprotein substrates for cell wall anchoring.", "mechanism": "Kaempferol inhibits SrtA, reducing S. pneumoniae virulence and meningitis severity.", "protein": "Sortase A (SrtA)", "protein_enriched": { "function": "Functions in the biosynthesis of branched-chain amino acids. Catalyzes the dehydration of (2R,3R)-2,3-dihydroxy-3-methylpentanoate (2,3-dihydroxy-3-methylvalerate) into 2-oxo-3-methylpentanoate (2-oxo", "gene_name": "ilvD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8DRT7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "PLY targets host glycoproteins for pore formation.", "mechanism": "Acacetin inhibits PLY oligomerization, reducing S. pneumoniae cytotoxicity.", "protein": "PLY", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627070" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG trigger demyelination and inflammation in the CNS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12627754" }, { "confidence": "medium", "disease": "ADEM", "glycan_involvement": "Glycosylation of MOG may influence immune recognition.", "mechanism": "MOG antibodies are associated with ADEM phenotype, especially in younger patients.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "RRMS", "glycan_involvement": "Glycosylation status may affect diagnostic specificity.", "mechanism": "MOG antibodies help distinguish MOGAD from RRMS; MOG is not a primary antigen in RRMS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Aquaporin-4 is glycosylated; glycan structures may modulate antibody binding.", "mechanism": "Autoantibodies against aquaporin-4 cause astrocyte damage and demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "MOGAD", "glycan_involvement": "Glycosylation may affect epitope exposure and antibody detection.", "mechanism": "Presence of anti-MOG antibodies is diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12627754" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may influence susceptibility of MOG to antibody-mediated injury.", "mechanism": "MOG antibody binding leads to white matter atrophy, especially in fornix and stria terminalis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12627754" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may modulate immune response and disease course.", "mechanism": "No evidence of progressive brain atrophy over time in early MOGAD, suggesting non-progressive neurodegeneration.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "protective (lack of progression)", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "RRMS", "glycan_involvement": "Not directly implicated.", "mechanism": "MOG is not a major antigen in RRMS; brain atrophy is associated with other mechanisms.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "non-causal", "source_pmcid": "PMC12627754" }, { "confidence": "medium", "disease": "MOGAD", "glycan_involvement": "Glycosylation may affect MOG stability and susceptibility to degeneration.", "mechanism": "WM atrophy in MOGAD may result from Wallerian degeneration after ADEM or tumefactive lesions.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal (Wallerian degeneration)", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "NMOSD", "glycan_involvement": "Glycosylation may affect antibody binding and disease specificity.", "mechanism": "Anti-aquaporin-4 antibodies are diagnostic for NMOSD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC12627754" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u00df is a glycoprotein; glycosylation may affect aggregation and clearance.", "mechanism": "A\u00df plaques are targeted by monoclonal antibodies to slow disease progression.", "protein": "Amyloid beta protein (A\u00df)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; glycosylation modulates aggregation and pathology.", "mechanism": "Tau abnormalities are targeted in combination therapies to address neurodegeneration.", "protein": "Tau protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect aggregation and toxicity.", "mechanism": "Alpha-synuclein aggregates are considered co-pathologies and therapeutic targets in AD.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "co-pathology/therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence aggregation and cellular localization.", "mechanism": "TDP-43 pathology is a co-pathology in AD and a target for combination therapies.", "protein": "TDP-43", "relationship_type": "co-pathology/therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect stability and function.", "mechanism": "GFAP levels decrease with anti-amyloid therapy, reflecting disease impact.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12627886" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate neurogranin function.", "mechanism": "Neurogranin changes reflect synaptic plasticity and disease progression.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for receptor function and trafficking.", "mechanism": "Used to shuttle monoclonal antibodies across the blood-brain barrier for AD therapy.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects lipid binding and receptor interactions.", "mechanism": "APOE4 allele increases risk for AD; used as a biomarker in trials.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "risk/biomarker", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "Cholinesterase inhibitors are used to enhance cognition in AD.", "protein": "Cholinesterase", "protein_enriched": { "function": "Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters", "gene_name": "BCHE", "glycan_count": 40, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G00912UN", "G01650EU", "G11314AS", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G37881RL", "G40574BA", "G41247ZX", "G59626AS", "G62765YT", "G80920RR", "G83646BJ", "G86795LJ", "G95865ZB", "G43089EG", "G70441OD", "G08918WF", "G27058EU", "G43223CG", "G11629QQ", "G12270AG", "G13694XX", "G15169WU", "G48414YA", "G55412XP", "G62461SM", "G81263BG", "G84452RH", "G28465XX", "G06247RL", "G27947YN", "G42466VF", "G45395BF", "G70232NH", "G70619PT", "G83460ZZ", "G49108TO" ], "uniprot_id": "P06276" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates receptor trafficking and function.", "mechanism": "NMDA receptor antagonists (e.g., memantine) are used to treat AD symptoms.", "protein": "N-methyl-D-aspartate receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12627886" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for stable secretion and function.", "mechanism": "Reduces endothelial dysfunction, inflammation, and apoptosis; inhibits ROS/p38 MAPK/NF-\u03baB pathway.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "N-glycosylation essential for secretion and stability.", "mechanism": "Reduces apoptosis, oxidative stress, ferroptosis; promotes angiogenesis and mitochondrial homeostasis.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation impacts circulating levels and function.", "mechanism": "Improves energy metabolism, reduces oxidative stress and apoptosis, correlates with better cardiac function.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycosylation required for secretion and neuroprotective effects.", "mechanism": "Reduces infarct size, neuroinflammation, apoptosis; activates PI3K/AKT/mTOR and ERK1/2 pathways.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12628017" }, { "confidence": "medium", "disease": "Hemorrhagic Stroke", "glycan_involvement": "N-glycosylation necessary for functional activity.", "mechanism": "Promotes anti-inflammatory microglial phenotype, inhibits MAPK/NF-\u03baB signaling.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12628017" }, { "confidence": "medium", "disease": "Post-Stroke Depression", "glycan_involvement": "N-glycosylation supports secretion and CNS effects.", "mechanism": "Upregulates BDNF/IGF-1, reduces NLRP3-mediated inflammation, improves depressive behavior.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Cardiac Ischemia-Reperfusion Injury", "glycan_involvement": "N-glycosylation required for secretion and cardioprotection.", "mechanism": "Preserves mitochondrial function, reduces ER stress and inflammation, activates autophagy.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12628017" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "N-glycosylation required for systemic effects.", "mechanism": "Improves endothelial function via PVAT modulation, reduces vascular dysfunction.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12628017" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "N-glycosylation affects circulating levels.", "mechanism": "Circulating Irisin levels predict sarcopenia risk; links muscle health to cardiovascular outcomes.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Cardiovascular Diseases (general)", "glycan_involvement": "N-glycosylation at Asn-7 and Asn-52 critical for Irisin secretion.", "mechanism": "FNDC5 cleavage and glycosylation regulate Irisin secretion, impacting multiple cardiovascular outcomes.", "protein": "FNDC5", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12628017" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Not directly discussed for CD4 itself.", "mechanism": "CD4+ T cells are implicated in disease initiation and progression.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Not directly discussed for CD4 itself.", "mechanism": "CD4+ T cells infiltrate inflamed tissue and are involved in disease pathology.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Not directly discussed for CD4 itself.", "mechanism": "Tumor-infiltrating CD4+ T cells contribute to antitumor immunity and response to immunotherapy.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Not directly discussed for CD4 itself.", "mechanism": "CD4+ T cell depletion is a hallmark of HIV/AIDS progression.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation at VL domain increases hepatic clearance, reducing lymphoid tissue uptake.", "mechanism": "Used for non-invasive imaging of CD4+ T cells in lymphoid and tumor tissues.", "protein": "GK1.5 FR cDb", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Removal of N-glycosylation restores renal clearance and increases target tissue uptake.", "mechanism": "Aglycosylated variant enables improved imaging of CD4+ T cells in lymphoid and tumor tissues.", "protein": "GK1.5 N80D cDb", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Aglycosylation improves biodistribution for imaging.", "mechanism": "Used to visualize CD4+ T cell infiltration in DSS-induced colitis mouse model.", "protein": "GK1.5 N80D cDb", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "medium", "disease": "Graft-versus-host disease", "glycan_involvement": "Aglycosylation improves imaging properties.", "mechanism": "Used to monitor CD4+ T cell repopulation after hematopoietic stem cell transplantation.", "protein": "GK1.5 N80D cDb", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation at VL domain increases hepatic clearance.", "mechanism": "Anti-CD8 cDb with N-glycosylation shows rapid hepatic clearance, limiting imaging of CD8+ T cells.", "protein": "YTS169 cDb", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Not specified.", "mechanism": "Humanized anti-CD4 minibody used for imaging CD4+ T cells in humanized mice and clinical translation.", "protein": "IAB41 minibody", "relationship_type": "imaging biomarker", "source_pmcid": "PMC12628392" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation of PF4 modulates its interaction with immune cells.", "mechanism": "PF4 levels correlate with amyloid pathology and cognitive decline.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker", "source_pmcid": "PMC12629908" }, { "confidence": "medium", "disease": "Age-related cognitive decline", "glycan_involvement": "N-glycosylation affects PF4's stability and receptor binding.", "mechanism": "PF4 influences microglial activation and synaptic pruning.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC12629908" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation at specific sites regulates APP processing.", "mechanism": "Aberrant glycosylation of APP promotes amyloid-beta aggregation.", "protein": "Amyloid Precursor Protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12629908" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sialylation changes impact iron transport and neurodegeneration.", "mechanism": "Altered glycoforms of transferrin detected in CSF of AD patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12629908" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for clusterin secretion and function.", "mechanism": "Clusterin modulates amyloid clearance; glycosylation affects its chaperone function.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC12629908" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates C3 activation and deposition.", "mechanism": "C3 activation drives neuroinflammatory cascades in aging brain.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12629908" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation status influences PF4's immune signaling.", "mechanism": "PF4 levels altered in PD; may reflect neuroimmune changes.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker", "source_pmcid": "PMC12629908" }, { "confidence": "high", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "cTn is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Elevated cTn indicates cardiomyocyte injury and predicts readmission/mortality risk.", "protein": "Cardiac troponin (cTn)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "high", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "Surface glycoproteins mediate neutrophil activation and migration.", "mechanism": "High NEU levels reflect inflammation, contributing to tissue injury and cardiac remodeling.", "protein": "Neutrophil (NEU) glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "high", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "Non-enzymatic glycosylation (glycation) of proteins forms AGEs, damaging cardiac tissue.", "mechanism": "Elevated FBG leads to accumulation of advanced glycation end-products (AGEs), promoting cardiac dysfunction.", "protein": "Fasting blood glucose (FBG)-related glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12630121" }, { "confidence": "medium", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "Albumin glycosylation status may affect its function and half-life.", "mechanism": "Low albumin (part of CALLY index) reflects poor nutritional/inflammatory status, associated with worse outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "medium", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "BNP is glycosylated, which may affect its secretion and activity.", "mechanism": "BNP is released in response to ventricular stretch and is predictive of CHF severity.", "protein": "Brain Natriuretic Peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "AGE formation via glycation of serum and tissue proteins.", "mechanism": "Chronic hyperglycemia leads to glycation of proteins, contributing to diabetic complications.", "protein": "Fasting blood glucose (FBG)-related glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12630121" }, { "confidence": "medium", "disease": "Ischemic Heart Disease", "glycan_involvement": "Glycoproteins mediate neutrophil-endothelial interactions.", "mechanism": "Neutrophil activation exacerbates tissue damage during ischemia.", "protein": "Neutrophil (NEU) glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12630121" }, { "confidence": "high", "disease": "Ischemic Heart Disease", "glycan_involvement": "Glycosylation may affect cTn release and detection.", "mechanism": "cTn elevation indicates myocardial injury in ischemic events.", "protein": "Cardiac troponin (cTn)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "medium", "disease": "Cardiorenal Syndrome (CRS)", "glycan_involvement": "Altered glycosylation may reflect disease severity.", "mechanism": "Low albumin is associated with poor outcomes in CRS due to inflammation and malnutrition.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate BNP activity.", "mechanism": "BNP levels rise in response to increased cardiac wall stress in hypertension.", "protein": "Brain Natriuretic Peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12630121" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may affect RNASE2 immunomodulatory function and stability.", "mechanism": "Elevated RNASE2 expression in PBMCs correlates with increased SLE disease activity and modulates IL-10 production by monocytes.", "protein": "RNASE2", "protein_enriched": { "function": "This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide v", "gene_name": "RNASE2", "glycan_count": 11, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00395TQ", "G39203UC", "G61491DK", "G35253PZ", "G45504EY", "G49955PK", "G57317CE", "G77547TA", "G31685JQ", "G49108TO", "G70323CJ" ], "uniprot_id": "P10153" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation influences PTGDS secretion and enzymatic activity.", "mechanism": "PTGDS downregulation in SLE PBMCs; urinary PTGDS levels correlate with lupus nephritis severity and proteinuria.", "protein": "PTGDS", "protein_enriched": { "function": "Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes", "gene_name": "PDE4D", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q08499" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may regulate CXCL2 stability and chemotactic activity.", "mechanism": "CXCL2 upregulation promotes neutrophil extracellular trap (NET) formation, contributing to SLE pathogenesis.", "protein": "CXCL2", "protein_enriched": { "function": "Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-", "gene_name": "CXCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19875" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates receptor function and apoptosis signaling.", "mechanism": "TNFRSF21 downregulation in SLE; higher expression in T-follicular helper cells correlates with disease activity in lupus-prone mice.", "protein": "TNFRSF21", "protein_enriched": { "function": "Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cyto", "gene_name": "TNFRSF21", "glycan_count": 10, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43417UB", "G48414YA", "G57888GL", "G57321FI", "G62765YT", "G22310AV", "G34730YF", "G84452RH", "G52527GH", "G02815KT" ], "uniprot_id": "O75509" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12630927" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation regulates LAMP3 subcellular localization and function.", "mechanism": "LAMP3 upregulation triggers apoptosis and autoantigen release, potentially contributing to SLE autoimmunity.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation affects LCN2 stability and immune interactions.", "mechanism": "LCN2 is a strong predictor in SLE diagnostic models; involved in immune modulation.", "protein": "LCN2", "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates adhesion and immune signaling.", "mechanism": "CEACAM8 included in diagnostic model; expression correlates with immune cell infiltration.", "protein": "CEACAM8", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion in a calcium-independent manner (PubMed:11590190, PubMed:2022629, PubMed:8776764). Mediates heterophilic cell adhesion with other carcinoem", "gene_name": "CEACAM8", "glycan_count": 10, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G77547TA", "G23432EQ", "G05724UK", "G06110VR", "G14669DU", "G39188ZX", "G05962QB", "G35541EV", "G67164EE", "G93718GY" ], "uniprot_id": "P31997" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation affects receptor function and IgE binding.", "mechanism": "FCER1A expression is altered in SLE and included in diagnostic model.", "protein": "FCER1A", "protein_enriched": { "function": "High-affinity receptor for immunoglobulin epsilon/IgE. Mediates IgE effector functions in myeloid cells. Upon IgE binding and antigen/allergen cross-linking initiates signaling pathways that lead to m", "gene_name": "FCER1A", "glycan_count": 3, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G22573RC", "G22768VO", "G81315DD" ], "uniprot_id": "P12319" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "IL1R2 expression is part of SLE diagnostic model; involved in inflammatory signaling.", "protein": "IL1R2", "protein_enriched": { "function": "Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competitive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular respons", "gene_name": "IL1R2", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G33791AF", "G37509XX", "G55412XP", "G56784JY", "G62461SM", "G70223PD", "G11629QQ", "G38663NM", "G48414YA" ], "uniprot_id": "P27930" }, "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may affect extracellular matrix interactions.", "mechanism": "TNFAIP6 expression correlates with neutrophil infiltration in SLE.", "protein": "TNFAIP6", "relationship_type": "biomarker", "source_pmcid": "PMC12630927" }, { "confidence": "high", "disease": "NS-PME", "glycan_involvement": "Indirect; vesicle trafficking defects may affect glycoprotein processing.", "mechanism": "Mutations in GOSR2 disrupt SNARE complex formation, impairing ER-Golgi vesicle trafficking in neurons.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "PMA/PME", "glycan_involvement": "Indirect; possible glycosylation defects in some variants.", "mechanism": "GOSR2 mutations (esp. c.430G>T) cause partial loss of SNARE function, leading to progressive myoclonus and ataxia.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "Congenital Muscular Dystrophy (CMD)", "glycan_involvement": "Hypoglycosylation of alpha-dystroglycan observed in muscle biopsies.", "mechanism": "Compound heterozygous GOSR2 mutations disrupt muscle-specific isoforms, impairing muscle function.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Not directly established; possible tissue-specific glycosylation effects.", "mechanism": "Specific GOSR2 mutations (e.g., c.1A>C) impair SNARE-mediated trafficking in auditory cells.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "medium", "disease": "CDG", "glycan_involvement": "Hypoglycosylation of alpha-dystroglycan and other glycoproteins.", "mechanism": "GOSR2 mutations lead to glycosylation defects, especially in compound heterozygotes.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "Reduced O-glycosylation impairs extracellular matrix binding.", "mechanism": "Hypoglycosylation of alpha-dystroglycan correlates with muscle pathology in CMD.", "protein": "Alpha-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "CDG", "glycan_involvement": "Defective glycoprotein processing in Golgi.", "mechanism": "Loss of short isoform of syntaxin-5 disrupts intra-Golgi trafficking, causing glycosylation defects.", "protein": "Syntaxin-5", "protein_enriched": { "function": "Mediates endoplasmic reticulum to Golgi transport. Together with p115/USO1 and GM130/GOLGA2, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connec", "gene_name": "STX5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13190" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "CDG", "glycan_involvement": "Global glycosylation defects due to trafficking failure.", "mechanism": "Bet1 mutations impair SNARE complex formation, leading to multisystem glycosylation defects.", "protein": "Bet1", "protein_enriched": { "function": "Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); inte", "gene_name": "EPS15L1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBC2" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "medium", "disease": "Cardiovascular anomalies", "glycan_involvement": "Not directly established.", "mechanism": "GOSR2 SNVs associated with increased risk of hypertension and myocardial infarction.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "risk factor", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "CMD + PMA/PME + Hearing loss (mixed phenotype)", "glycan_involvement": "Hyperglycosylation/hypoglycosylation of alpha-dystroglycan observed.", "mechanism": "Compound heterozygous mutations affect multiple isoforms, leading to multisystem involvement.", "protein": "GOSR2", "protein_enriched": { "function": "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans ", "gene_name": "PPIL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12631098" }, { "confidence": "high", "disease": "RVO-ME", "glycan_involvement": "Glycosylation affects secretion and stability; altered glycosylation may modulate activity in disease.", "mechanism": "Promotes vascular leakage and inflammation; levels correlate positively with macular edema severity and BCVA loss.", "protein": "Plasma kallikrein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12631356" }, { "confidence": "high", "disease": "RVO-ME", "glycan_involvement": "O-glycosylation critical for cell adhesion; increased glycosylation may enhance barrier function.", "mechanism": "Upregulated during edema resolution; negatively correlated with macular edema severity, suggesting barrier repair.", "protein": "Desmocollin-3", "protein_enriched": { "function": "This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. May in", "gene_name": "ERVW-1", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9UQF0" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "O-glycosylation modulates adhesive properties; changes may impact vascular integrity.", "mechanism": "Negatively correlated with macular edema severity and BCVA loss; may indicate endothelial repair.", "protein": "Desmocollin-2", "protein_enriched": { "function": "A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (By similarity). Required for desmosome adhesion strength between the granular layers of th", "gene_name": "DSC1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q08554" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "N-glycosylation influences ECM interactions; altered glycosylation may promote fibrosis.", "mechanism": "Associated with retinal fibrosis; inversely correlated with edema severity.", "protein": "SPARC", "relationship_type": "biomarker/fibrosis risk", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "N-glycosylation affects receptor function; may modulate anti-fibrotic activity.", "mechanism": "Negatively correlated with macular edema severity; linked to tissue remodeling.", "protein": "Vasorin", "protein_enriched": { "function": "May act as an inhibitor of TGF-beta signaling", "gene_name": "VASN", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04657PL", "G07246CJ", "G08918WF", "G10486CT", "G13131HA", "G14972EH", "G20312EM", "G22310AV", "G27058EU", "G33791AF", "G34989PA", "G41071NU", "G43223CG", "G45395BF", "G48414YA", "G50045TK", "G57776ZS", "G59626AS", "G61256FT", "G62765YT", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G75568BH", "G76295SF", "G77582RK", "G79666IR", "G80075MS", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G85282JO", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92135MA", "G98611JV", "G57321FI", "G43417UB", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G38663NM", "G39188ZX", "G41247ZX", "G64527OM", "G49108TO" ], "uniprot_id": "Q6EMK4" }, "relationship_type": "biomarker/fibrosis risk", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "N-glycosylation required for cell-cell interaction; altered glycosylation may affect neuroprotection.", "mechanism": "Negatively correlated with BCVA loss and edema severity; may reflect neural repair.", "protein": "Neurotrimin", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "N-glycosylation modulates ECM assembly; changes may promote fibrotic remodeling.", "mechanism": "Associated with retinal fibrosis; inversely correlated with edema severity.", "protein": "Fibulin-1", "relationship_type": "biomarker/fibrosis risk", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "CRVO", "glycan_involvement": "N-glycosylation affects secretion and activity; may influence fibrotic signaling.", "mechanism": "Linked to fibrosis; inversely correlated with edema severity.", "protein": "Follistatin-related protein 1", "relationship_type": "biomarker/fibrosis risk", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "RVO-ME", "glycan_involvement": "Heavily N-glycosylated; glycan structures mediate immune cell interactions.", "mechanism": "Upregulated in RVO; involved in immune response and ECM remodeling.", "protein": "Galectin-3-binding protein", "relationship_type": "biomarker/inflammatory", "source_pmcid": "PMC12631356" }, { "confidence": "medium", "disease": "RVO-ME", "glycan_involvement": "N-glycosylation modulates complement regulation; changes may affect inflammation.", "mechanism": "Regulates complement activation; altered levels reflect immune dysregulation in RVO.", "protein": "Complement factor H", "relationship_type": "biomarker/inflammatory", "source_pmcid": "PMC12631356" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG cause CNS demyelination and inflammation.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC12631793" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation may influence MOG-IgG detection and immune response.", "mechanism": "Presence of MOG-IgG in CSF is a diagnostic marker for MOGAD.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12631793" }, { "confidence": "high", "disease": "Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD)", "glycan_involvement": "AQP4 is glycosylated; glycan structures may affect antibody recognition.", "mechanism": "Autoantibodies against AQP4 cause astrocyte damage and demyelination.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12631793" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "FcRn glycosylation may modulate receptor function and viral binding.", "mechanism": "FcRn acts as a receptor for echoviruses, facilitating viral entry into meninges.", "protein": "Neonatal Fc receptor (FcRn)", "protein_enriched": { "function": "Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degrad", "gene_name": "DET1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7L5Y6" }, "relationship_type": "causal", "source_pmcid": "PMC12631793" }, { "confidence": "medium", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "Glycosylation affects FcRn-IgG interactions.", "mechanism": "FcRn mediates IgG transport across CNS barriers; targeting FcRn may modulate pathogenic IgG levels.", "protein": "Neonatal Fc receptor (FcRn)", "protein_enriched": { "function": "Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degrad", "gene_name": "DET1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7L5Y6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12631793" }, { "confidence": "medium", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "IL-6R glycosylation may influence receptor signaling and drug binding.", "mechanism": "IL-6R blockade may restore blood-brain and blood-leptomeningeal barrier integrity, reducing inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12631793" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may affect MOG antigenicity in MS.", "mechanism": "MOG antibodies are less common in MS but may be present in some cases.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12631793" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation modulates FcRn function.", "mechanism": "FcRn may regulate IgG export from CNS, influencing immune privilege and inflammation.", "protein": "Neonatal Fc receptor (FcRn)", "protein_enriched": { "function": "Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degrad", "gene_name": "DET1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7L5Y6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12631793" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may affect antibody detection.", "mechanism": "MOG-IgG may be detected in CSF during aseptic meningitis in MOGAD patients.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12631793" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Glycosylation may affect IL-6R function.", "mechanism": "IL-6 increases endothelial permeability; blocking IL-6R may reduce meningeal inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12631793" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against MOG trigger CNS demyelination and inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12631794" }, { "confidence": "high", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "Glycosylation of MOG may influence antibody recognition.", "mechanism": "Presence of anti-MOG antibodies is diagnostic for MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12631794" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation differences may affect immune recognition.", "mechanism": "Anti-MOG antibodies are rare in MS, distinguishing it from MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12631794" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may modulate antibody binding.", "mechanism": "Autoantibodies against AQP4 cause NMOSD via astrocyte injury.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12631794" }, { "confidence": "medium", "disease": "Seronegative myelitis", "glycan_involvement": "Not directly involved.", "mechanism": "Absence of anti-MOG antibodies helps define seronegative myelitis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC12631794" }, { "confidence": "medium", "disease": "Myelin oligodendrocyte glycoprotein antibody\u2013associated disease (MOGAD)", "glycan_involvement": "MOG glycosylation may influence immune complex formation and inflammation.", "mechanism": "Spinal cord leptomeningeal enhancement (LME) is a marker of extensive spinal cord involvement in MOGAD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12631794" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Not directly involved.", "mechanism": "AQP4 antibodies are rarely present in MS, distinguishing it from NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC12631794" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "PG glycan-peptide structure required for NOD1 activation.", "mechanism": "Recognition of glutamate-mDAP moiety in bacterial PG triggers inflammatory response.", "protein": "NOD1", "protein_enriched": { "function": "Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses (PubMed:11058605, PubMed:1", "gene_name": "NOD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y239" }, "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "NAM glycan with peptide required for NOD2 activation.", "mechanism": "Recognition of muramyl dipeptide (MDP) from PG activates NOD2 signaling, influencing gut inflammation.", "protein": "NOD2", "protein_enriched": { "function": "Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity (PubMed:12514169, PubMed:12527755, P", "gene_name": "NOD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HC29" }, "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "medium", "disease": "Microbiome Dysbiosis", "glycan_involvement": "Recognition of PG glycan-peptide motifs.", "mechanism": "PGRP regulates bacterial species composition in the gut, preventing overgrowth of pathogenic bacteria.", "protein": "PGRP", "relationship_type": "protective", "source_pmcid": "PMC12632261" }, { "confidence": "high", "disease": "Antimicrobial Resistance", "glycan_involvement": "Crosslinking of PG glycan-peptide chains.", "mechanism": "Forms 3\u20133 crosslinks in PG, maintaining cell wall integrity during \u03b2-lactam antibiotic stress.", "protein": "L,D-transpeptidase", "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "medium", "disease": "Immune Evasion", "glycan_involvement": "Modification of PG peptide side chain.", "mechanism": "Amidation of PG stem peptide reduces recognition by host NOD receptors.", "protein": "GatD/MurT complex", "relationship_type": "protective", "source_pmcid": "PMC12632261" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "NAG glycan fragment required for activation.", "mechanism": "Detects NAG from PG, activating NLRP3 inflammasome.", "protein": "Hexokinase", "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "low", "disease": "Neurodevelopmental Disorders", "glycan_involvement": "Transport of PG glycan-peptide fragments.", "mechanism": "Transports muropeptides from gut to brain, influencing development and behavior.", "protein": "PepT1 (SLC15A1)", "protein_enriched": { "function": "Proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides (PubMed:16434549, PubMed:18367661, PubMed:7756356). Transports neutral and an", "gene_name": "SLC15A2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q16348" }, "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "medium", "disease": "Immune Evasion", "glycan_involvement": "Altered PG peptide composition.", "mechanism": "Leaky incorporation of non-canonical amino acids into PG reduces host immune recognition.", "protein": "MurE", "relationship_type": "protective", "source_pmcid": "PMC12632261" }, { "confidence": "medium", "disease": "Bacterial Infection", "glycan_involvement": "Cleavage of PG glycan backbone.", "mechanism": "Release of PG fragments during infection triggers host immune response.", "protein": "Lytic transglycosylases (e.g., MltE, MltC)", "relationship_type": "causal", "source_pmcid": "PMC12632261" }, { "confidence": "high", "disease": "Lysozyme Resistance", "glycan_involvement": "O-acetylation of glycan chain.", "mechanism": "O-acetylation of PG backbone prevents lysozyme-mediated digestion.", "protein": "PG O-acetylation", "relationship_type": "protective", "source_pmcid": "PMC12632261" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation patterns on E2 affect antigenicity and cross-neutralization.", "mechanism": "Target of neutralizing antibodies elicited by rAAV1-CHIKV-SP vaccine, conferring protection.", "protein": "CHIKV E2 glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12633881" }, { "confidence": "medium", "disease": "Chikungunya fever", "glycan_involvement": "Altered glycosylation at E2-E1 interface may enable immune escape.", "mechanism": "E1 forms heterodimers with E2; antibodies targeting E1-E2 interface contribute to neutralization.", "protein": "CHIKV E1 glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12633881" }, { "confidence": "medium", "disease": "Chronic chikungunya arthritis", "glycan_involvement": "Glycosylation may modulate immunogenicity and chronicity.", "mechanism": "Persistent immune response to E2 correlates with chronic joint inflammation.", "protein": "CHIKV E2 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12633881" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Capsid glycan motifs are targets for neutralizing antibodies.", "mechanism": "Pre-existing anti-AAV antibodies can block vaccine vector transduction, reducing efficacy.", "protein": "AAV capsid proteins (VP3 domain)", "relationship_type": "protective", "source_pmcid": "PMC12633881" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy", "glycan_involvement": "Complement activation involves glycoprotein cleavage and opsonization.", "mechanism": "Elevated C3a/C5a and complement consumption linked to microangiopathy after high-dose AAV.", "protein": "Complement proteins (C3a, C5a)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12633881" }, { "confidence": "low", "disease": "Hypoalbuminaemia", "glycan_involvement": "Albumin glycosylation status may affect plasma stability.", "mechanism": "Complement consumption-induced hypoalbuminaemia observed post-AAV infusion.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12633881" }, { "confidence": "high", "disease": "Chikungunya fever (IOL strain)", "glycan_involvement": "Mutation may alter glycosylation, affecting antibody recognition.", "mechanism": "E2-K233R substitution leads to antigenic drift and potential vaccine escape.", "protein": "CHIKV E2 glycoprotein (K233R variant)", "relationship_type": "causal", "source_pmcid": "PMC12633881" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation diversity impacts cross-strain protection.", "mechanism": "Conserved epitopes on E2-E1 heterodimer are targets for broadly neutralizing antibodies.", "protein": "CHIKV E2-E1 heterodimer", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12633881" }, { "confidence": "medium", "disease": "Infusion-related fever/chills", "glycan_involvement": "Capsid glycan motifs may activate innate immunity.", "mechanism": "Innate immune response to AAV capsid glycoproteins triggers fever/chills.", "protein": "AAV capsid proteins", "relationship_type": "causal", "source_pmcid": "PMC12633881" }, { "confidence": "high", "disease": "Chikungunya fever (Asian/IOL strains)", "glycan_involvement": "Altered glycosylation can mask neutralizing epitopes.", "mechanism": "Vaccine-induced antibodies may have reduced efficacy due to E2 glycosylation pattern diversity.", "protein": "CHIKV E2 glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12633881" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation at 7 sites in the C-terminus is essential for NANOG's function in stemness and proliferation.", "mechanism": "NANOG maintains stemness and proliferation of colon cancer stem cells.", "protein": "NANOG", "relationship_type": "causal", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Deletion of N-glycosylation sites reduces proliferation, migration, and sphere formation.", "mechanism": "Targeting N-glycosylation of NANOG impairs stem cell characteristics and tumorigenic potential.", "protein": "NANOG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12633897" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "High N-glycosylation of NANOG is associated with aggressive cancer stem cell behavior.", "mechanism": "NANOG N-glycosylation status correlates with stemness and poor prognosis.", "protein": "NANOG", "relationship_type": "biomarker", "source_pmcid": "PMC12633897" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "OST-A mediates N-glycosylation of NANOG and other proteins.", "mechanism": "Upregulation of OST-A correlates with increased N-glycosylation in tumor tissue.", "protein": "OST-A (STT3A)", "relationship_type": "biomarker", "source_pmcid": "PMC12633897" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "OST-B mediates N-glycosylation of NANOG and other proteins.", "mechanism": "Upregulation of OST-B correlates with increased N-glycosylation in tumor tissue.", "protein": "OST-B (STT3B)", "protein_enriched": { "function": "GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has a substantial GAP activity toward CDC42 and RAC1 and less toward RHOA. Has a role in regulating adhesio", "gene_name": "ARHGAP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BRR9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation increases Bax/Bcl-2 ratio, promoting apoptosis.", "mechanism": "N-glycosylation of NANOG enhances apoptosis in colon cancer stem cells.", "protein": "NANOG", "relationship_type": "causal", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Loss of N-glycosylation sites reduces migration.", "mechanism": "N-glycosylation of NANOG regulates migration ability of colon cancer stem cells.", "protein": "NANOG", "relationship_type": "causal", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Loss of N-glycosylation sites reduces sphere diameter and number.", "mechanism": "N-glycosylation of NANOG regulates sphere formation (stemness) in colon cancer stem cells.", "protein": "NANOG", "relationship_type": "causal", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "N-glycans at C-terminus regulate folding and stability.", "mechanism": "N-glycosylation of NANOG is involved in molecular quality control and protein stability.", "protein": "NANOG", "relationship_type": "causal", "source_pmcid": "PMC12633897" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "High expression of N-glycosylation enzymes and NANOG N-glycosylation correlates with poor outcome.", "mechanism": "Abnormal N-glycosylation predicts poor prognosis in CRC patients.", "protein": "NANOG", "relationship_type": "biomarker", "source_pmcid": "PMC12633897" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gn is a glycoprotein; glycosylation is essential for receptor binding and immune evasion.", "mechanism": "Gn mediates viral binding to host cell receptors, facilitating entry and infection.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Gc is a glycoprotein; glycosylation affects fusion efficiency and immune recognition.", "mechanism": "Gc mediates fusion of viral and endosomal membranes, enabling viral genome entry.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation status may modulate tissue tropism.", "mechanism": "Mutations in Gn may alter tropism and enhance viral entry into multiple cell types.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation may influence fusion and spread.", "mechanism": "Mutations in Gc may affect membrane fusion and viral dissemination.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation sites may be altered by mutations, impacting antigenicity.", "mechanism": "Gn mutations serve as molecular markers for genotype and virulence.", "protein": "Gn glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation changes may affect immune detection.", "mechanism": "Gc mutations are used for genotyping and may correlate with disease severity.", "protein": "Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "No direct glycosylation reported for NP in this article.", "mechanism": "NP is essential for viral genome protection and replication.", "protein": "Nucleocapsid protein (NP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "No direct glycosylation reported for NSs in this article.", "mechanism": "NSs suppress host interferon response, enhancing viral replication and immune evasion.", "protein": "Non-structural protein (NSs)", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "low", "disease": "Disseminated intravascular coagulation", "glycan_involvement": "Glycosylation may modulate pathogenicity.", "mechanism": "Enhanced viral entry via Gn may contribute to severe disease complications.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "low", "disease": "Disseminated intravascular coagulation", "glycan_involvement": "Glycosylation may affect fusion and immune response.", "mechanism": "Altered fusion activity may exacerbate systemic infection.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12634303" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "gp100 is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "gp100 is recognized by tumor-specific lymphocytes in melanoma, indicating immune recognition.", "protein": "gp100", "relationship_type": "biomarker", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation may modulate antigen presentation.", "mechanism": "Melan-A is a melanoma antigen recognized by T cells, used in diagnosis and immune response.", "protein": "Melan-A/MART-1", "protein_enriched": { "function": "Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the", "gene_name": "MLANA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16655" }, "relationship_type": "biomarker", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation affects stability and immune recognition.", "mechanism": "Tyrosinase is a melanocyte differentiation antigen targeted by immune cells in melanoma.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12634356" }, { "confidence": "medium", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation may influence antigen processing.", "mechanism": "TRP-1 is a melanocyte antigen recognized by tumor-specific lymphocytes.", "protein": "TRP-1", "protein_enriched": { "function": "Plays a role in melanin biosynthesis (PubMed:16704458, PubMed:22556244, PubMed:23504663). Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic ", "gene_name": "TYRP1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22768VO", "G07617FP", "G82348BZ", "G22573RC", "G56014GC", "G99801SM" ], "uniprot_id": "P17643" }, "relationship_type": "biomarker", "source_pmcid": "PMC12634356" }, { "confidence": "medium", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation may influence antigen processing.", "mechanism": "TRP-2 is a melanocyte antigen recognized by tumor-specific lymphocytes.", "protein": "TRP-2", "protein_enriched": { "function": "Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:274628", "gene_name": "EIF3K", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBQ5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation modulates PD-1 stability and ligand binding.", "mechanism": "PD-1 is targeted by immunotherapy (nivolumab, pembrolizumab) to enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation affects PD-L1 expression and immune checkpoint function.", "mechanism": "PD-L1 is targeted by immunotherapy to block immune evasion by tumor cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Orbital melanoma", "glycan_involvement": "Glycosylation modulates CTLA-4 surface expression and function.", "mechanism": "CTLA-4 is targeted by ipilimumab to enhance T cell activation against melanoma.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12634356" }, { "confidence": "high", "disease": "Chronic viral infection (Orsay virus)", "glycan_involvement": "SUMOylation (not classical glycosylation) regulates DRH-1 stability and function.", "mechanism": "Loss of DRH-1 impairs antiviral defense, leading to persistent viral infection.", "protein": "DRH-1 (RIG-I ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Chronic viral infection (Orsay virus)", "glycan_involvement": "ULP-4 removes SUMO (SMO-1) from DRH-1, regulating its activity.", "mechanism": "Loss of ULP-4 prevents deSUMOylation of DRH-1, compromising antiviral defense.", "protein": "ULP-4 (SENP7 ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Intestinal pathogenesis", "glycan_involvement": "SUMOylation status affects DRH-1 degradation and localization.", "mechanism": "DRH-1 deficiency leads to viral persistence and intestinal bloating.", "protein": "DRH-1 (RIG-I ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Intestinal pathogenesis", "glycan_involvement": "DeSUMOylation of DRH-1 by ULP-4 is required for defense.", "mechanism": "ULP-4 loss results in impaired DRH-1 function and increased pathogenesis.", "protein": "ULP-4 (SENP7 ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "SUMOylation of lysines K647/K731 increases with age, promoting DRH-1 degradation.", "mechanism": "Aging increases DRH-1 SUMOylation, reducing antiviral response.", "protein": "DRH-1 (RIG-I ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "Reduced deSUMOylation of DRH-1 in aged animals.", "mechanism": "Age-related decline in ULP-4 expression leads to impaired DRH-1 deSUMOylation and immune response.", "protein": "ULP-4 (SENP7 ortholog)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Chronic viral infection (Orsay virus)", "glycan_involvement": "Preventing SUMOylation at specific lysines preserves DRH-1 function.", "mechanism": "Mutation of SUMOylation sites (K647R/K731R) on DRH-1 restores antiviral defense in aged animals.", "protein": "DRH-1 (RIG-I ortholog)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12635358" }, { "confidence": "medium", "disease": "Immunosenescence", "glycan_involvement": "SUMOylation modifies multiple proteins, including DRH-1.", "mechanism": "Global hyper-SUMOylation during aging impairs stress responses including antiviral defense.", "protein": "SMO-1 (SUMO moiety)", "relationship_type": "causal", "source_pmcid": "PMC12635358" }, { "confidence": "medium", "disease": "Chronic viral infection (Orsay virus)", "glycan_involvement": "SUMOylation by GEI-17 limits DRH-1 activation.", "mechanism": "Loss of GEI-17 (SUMO E3 ligase) increases IPR induction and antiviral defense.", "protein": "GEI-17 (SUMO E3 ligase)", "relationship_type": "protective", "source_pmcid": "PMC12635358" }, { "confidence": "medium", "disease": "Intestinal pathogenesis", "glycan_involvement": "SUMOylation status can be monitored as a biomarker for antiviral capacity.", "mechanism": "DRH-1 protein levels and SUMOylation status correlate with disease severity.", "protein": "DRH-1 (RIG-I ortholog)", "relationship_type": "biomarker", "source_pmcid": "PMC12635358" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation may affect secretion and matrix interactions.", "mechanism": "Associated with elastic fiber formation and extracellular matrix remodeling in atria.", "protein": "Microfibril-associated glycoprotein 4", "protein_enriched": { "function": "Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN (PubMed:18185537). Stabilizes and organizes ", "gene_name": "FBLN5", "glycan_count": 84, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G71142DF", "G00273SJ", "G01485JJ", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G10488MI", "G11314AS", "G14972EH", "G17208MA", "G18647XP", "G20706XG", "G23719VF", "G23863VK", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G29299MO", "G31852PQ", "G34029GR", "G35029YA", "G35253PZ", "G36379GD", "G37399XV", "G37509XX", "G39446WN", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G46450MZ", "G46687AB", "G46691LC", "G47644PP", "G49589RB", "G49906RN", "G57317CE", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G77669RF", "G79666IR", "G80075MS", "G80669SJ", "G80920RR", "G81198YO", "G83460ZZ", "G83633GK", "G84452RH", "G84862VB", "G85282JO", "G87123QX", "G87389XI", "G90382BL", "G90659AW", "G92275SC", "G92406TI", "G95177YH", "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q9UBX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Heavily glycosylated; glycosylation critical for function.", "mechanism": "Upregulated in AF; involved in protein glycosylation pathways.", "protein": "Keratocan", "protein_enriched": { "function": "Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Also acts as a ligand for CMKLR2. Can also", "gene_name": "RARRES2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q99969" }, "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Secreted glycoprotein; glycosylation may regulate stability.", "mechanism": "Top upregulated protein in AF; regulated by TGF-\u03b2 signaling, may influence fibrosis.", "protein": "Olfactomedin-like protein 3", "protein_enriched": { "function": "Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis", "gene_name": "CCBE1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G71142DF", "G49108TO" ], "uniprot_id": "Q6UXH8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation may modulate cell adhesion properties.", "mechanism": "Linked to extracellular matrix organization and Alzheimer\u2019s-related pathways.", "protein": "Spondin 1", "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Heavily N-glycosylated; glycosylation regulates cell surface expression.", "mechanism": "Upregulated in AF; involved in extracellular matrix remodeling.", "protein": "Basigin (CD147)", "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "Associated with protein glycosylation and matrix assembly.", "protein": "ADAMTS-like 2", "protein_enriched": { "function": "", "gene_name": "ADAMTS18", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8TE60" }, "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Secreted glycoprotein; glycosylation modulates bioactivity.", "mechanism": "Upregulated in AF; involved in cardiac remodeling.", "protein": "Insulin-like growth factor-binding protein 7", "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation may affect matrix incorporation.", "mechanism": "Linked to elastic fiber formation and atrial fibrosis.", "protein": "Fibulin 5", "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "N-glycosylation modulates ligand binding.", "mechanism": "Associated with nervous system development pathways in AF.", "protein": "Neuropilin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Catalyzes sulfation of glycan chains.", "mechanism": "Involved in glycosaminoglycan modification; upregulated in AF.", "protein": "Carbohydrate sulfotransferase 15", "protein_enriched": { "function": "Sulfotransferase that transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of the GalNAc 4-sulfate residue of chondroitin sulfate A and forms chondroitin sulfa", "gene_name": "CHST15", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G80920RR" ], "uniprot_id": "Q7LFX5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12635735" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin is part of the DGC, which contains glycoproteins essential for membrane stability.", "mechanism": "Upregulation of utrophin compensates for dystrophin deficiency, stabilizing the sarcolemma and improving muscle function.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycoproteins in the DGC, affecting glycosylation-dependent membrane integrity.", "mechanism": "Loss of dystrophin due to gene mutation causes DMD by destabilizing muscle cell membranes.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b1-sarcoglycan is a glycoprotein whose glycosylation is critical for DGC assembly and function.", "mechanism": "\u03b1-sarcoglycan levels reflect DGC stabilization and functional rescue in DMD models.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636391" }, { "confidence": "medium", "disease": "Muscle inflammation", "glycan_involvement": "Glycosylated DGC components mediate anti-inflammatory effects via membrane stabilization.", "mechanism": "Utrophin upregulation reduces inflammatory infiltration in dystrophic muscle.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC12636391" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation of DGC proteins is required for proper extracellular matrix interactions.", "mechanism": "Utrophin induction attenuates muscle fibrosis in mdx mice.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC12636391" }, { "confidence": "medium", "disease": "Muscle inflammation", "glycan_involvement": "Glycosylation status affects \u03b1-sarcoglycan stability and anti-inflammatory function.", "mechanism": "Increased \u03b1-sarcoglycan correlates with reduced muscle inflammation after utrophin activation.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylated utrophin interacts with DGC glycoproteins for membrane repair.", "mechanism": "Endogenous utrophin re-expression at the sarcolemma improves early-stage muscle function in DMD.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective", "source_pmcid": "PMC12636391" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "Glycosylation is essential for \u03b1-sarcoglycan's role in extracellular matrix modulation.", "mechanism": "\u03b1-sarcoglycan upregulation is associated with reduced fibrosis in utrophin-activated muscle.", "protein": "\u03b1-sarcoglycan", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1S4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation influences utrophin's stability and localization at the sarcolemma.", "mechanism": "Utrophin levels serve as a biomarker for therapeutic efficacy in DMD gene therapy.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Muscle inflammation", "glycan_involvement": "Loss of DGC glycoprotein interactions exacerbates inflammatory response.", "mechanism": "Dystrophin deficiency leads to increased muscle inflammation due to membrane instability.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12636391" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Heparan sulfate/chondroitin sulfate chains are cleaved, releasing glycosylated fragments.", "mechanism": "Syndecan-1 ectodomain is shed by MMPs/ADAM17 during sepsis, disrupting endothelial junctions and amplifying inflammation.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12636855" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosaminoglycan fragmentation increases inflammatory signaling.", "mechanism": "HA is degraded into low-molecular-weight fragments by hyaluronidases, which act as pro-inflammatory mediators and predict mortality.", "protein": "Hyaluronic acid (HA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12636855" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Shedding of glycosylated ectodomain reflects eGC breakdown.", "mechanism": "Elevated circulating syndecan-1 correlates with ICU admission and multi-organ dysfunction.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636855" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "GAG degradation products act as biomarkers.", "mechanism": "Elevated HA levels are associated with severe disease and organ dysfunction.", "protein": "Hyaluronic acid (HA)", "relationship_type": "biomarker", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Cognitive dysfunction (septic)", "glycan_involvement": "Glycosaminoglycan fragments mediate neuroinflammation.", "mechanism": "HS fragments penetrate hippocampus, inhibit BDNF, contributing to septic cognitive dysfunction.", "protein": "Heparan sulfate (HS)", "relationship_type": "causal", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Shedding of glycosylated CD44 reflects eGC breakdown.", "mechanism": "MMP15 knockdown reduces LPS-induced CD44 shedding, indicating eGC injury.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylated fragments in urine indicate eGC damage.", "mechanism": "Urinary syndecan-1 levels serve as early markers of renal injury.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "GAG fragments in urine indicate eGC breakdown.", "mechanism": "Urinary HA levels reflect renal endothelial injury.", "protein": "Hyaluronic acid (HA)", "relationship_type": "biomarker", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Loss of glycosylated syndecan-4 disrupts eGC barrier.", "mechanism": "MMP-mediated shedding of syndecan-4 increases endothelial permeability in glomerular cells.", "protein": "Syndecan-4", "protein_enriched": { "function": "Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413)", "gene_name": "SDC4", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "P31431" }, "relationship_type": "causal", "source_pmcid": "PMC12636855" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Cleavage of HS chains alters chemokine gradients and endothelial function.", "mechanism": "HS degradation by heparanase-1 disrupts eGC integrity, promoting vascular dysfunction.", "protein": "Heparan sulfate (HS)", "relationship_type": "causal", "source_pmcid": "PMC12636855" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum levels and diagnostic specificity.", "mechanism": "AFP is elevated in HCC and used for screening in cirrhosis patients.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12637340" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation of AFP may influence its stability and detection.", "mechanism": "AFP is measured in cirrhosis patients for HCC risk assessment.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12637340" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "YKL-40 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "YKL-40 levels reflect hepatic inflammation and fibrosis activity.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates YKL-40's extracellular matrix interactions.", "mechanism": "Elevated YKL-40 correlates with fibrosis stage and regression/progression.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Panel includes YKL-40, a glycoprotein; glycosylation is relevant for its biomarker function.", "mechanism": "Serial NIS2+\u00ae measurements track disease activity and resolution.", "protein": "NIS2+\u00ae panel", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "YKL-40 glycosylation influences panel performance.", "mechanism": "NIS2+\u00ae score changes associate with fibrosis regression or progression.", "protein": "NIS2+\u00ae panel", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may affect YKL-40's role in fibrogenesis.", "mechanism": "YKL-40 levels increase with advanced fibrosis and cirrhosis.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation impacts YKL-40's stability and detection.", "mechanism": "YKL-40 is elevated in MASLD and tracks progression to MASH.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "YKL-40 glycosylation is integral to panel accuracy.", "mechanism": "NIS2+\u00ae identifies at-risk MASLD patients for progression to MASH.", "protein": "NIS2+\u00ae panel", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate YKL-40's fibrogenic activity.", "mechanism": "YKL-40 may contribute to extracellular matrix remodeling.", "protein": "YKL-40", "relationship_type": "therapeutic target (potential)", "source_pmcid": "PMC12637350" }, { "confidence": "low", "disease": "MASH", "glycan_involvement": "Glycosylation could affect YKL-40's receptor binding.", "mechanism": "YKL-40 may participate in hepatic inflammation and fibrogenesis.", "protein": "YKL-40", "relationship_type": "causal (potential)", "source_pmcid": "PMC12637350" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "YKL-40 glycosylation relevant for detection.", "mechanism": "NIS2+\u00ae may detect progression to cirrhosis via YKL-40 elevation.", "protein": "NIS2+\u00ae panel", "relationship_type": "biomarker", "source_pmcid": "PMC12637350" }, { "confidence": "high", "disease": "AOSD", "glycan_involvement": "Ferritin is glycosylated, which may affect its stability and clearance.", "mechanism": "Ferritin is markedly elevated in AOSD due to systemic inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "HLH", "glycan_involvement": "Glycosylation may influence ferritin's serum half-life.", "mechanism": "Extreme hyperferritinemia is a diagnostic clue for HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "HLH", "glycan_involvement": "sCD25 is N-glycosylated, affecting its secretion and detection.", "mechanism": "Elevated sCD25 reflects T-cell activation in HLH.", "protein": "Soluble IL-2 receptor (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "Graves\u2019 Disease", "glycan_involvement": "TSH receptor glycosylation modulates antibody binding and receptor function.", "mechanism": "Autoantibodies stimulate the TSH receptor, causing thyrotoxicosis.", "protein": "TSH receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "Graves\u2019 Disease", "glycan_involvement": "Antibody glycosylation affects effector function and clearance.", "mechanism": "Presence indicates autoimmune thyroid stimulation.", "protein": "Anti-TSH receptor antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "AOSD", "glycan_involvement": "N-glycosylation modulates receptor stability and ligand binding.", "mechanism": "IL-1 signaling drives inflammation; antagonism (anakinra) is effective.", "protein": "Interleukin-1 receptor", "protein_enriched": { "function": "Receptor for IL1A, IL1B and IL1RN (PubMed:2950091, PubMed:37315560). After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which", "gene_name": "IL1R1", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P14778" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12637999" }, { "confidence": "medium", "disease": "AOSD", "glycan_involvement": "Glycosylation affects receptor function and cytokine binding.", "mechanism": "IL-6 receptor signaling contributes to systemic inflammation.", "protein": "Interleukin-6 receptor", "relationship_type": "causal", "source_pmcid": "PMC12637999" }, { "confidence": "medium", "disease": "AOSD", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "TNF receptor signaling is implicated in autoinflammatory processes.", "protein": "Tumor necrosis factor receptor", "relationship_type": "causal", "source_pmcid": "PMC12637999" }, { "confidence": "medium", "disease": "Thyroiditis", "glycan_involvement": "Glycosylation may alter immune recognition during inflammation.", "mechanism": "Transient anti-TSH receptor antibody positivity may reflect inflammation-induced thyroid dysfunction.", "protein": "TSH receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "medium", "disease": "Cytopenia", "glycan_involvement": "Glycosylation may affect ferritin's immunogenicity.", "mechanism": "Elevated ferritin correlates with severity of cytopenia in HLH/AOSD.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12637999" }, { "confidence": "high", "disease": "Acute decompensated heart failure", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in ADHF, reflecting systemic inflammation and predicting adverse outcomes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Acute decompensated heart failure", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect its half-life and antioxidant properties.", "mechanism": "Low albumin levels are associated with increased mortality in ADHF, reflecting poor nutritional and inflammatory status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in DM, indicating chronic low-grade inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation status may be altered in DM, impacting albumin function.", "mechanism": "Hypoalbuminemia is common in DM and predicts worse cardiovascular outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Major adverse cardiac and cerebrovascular events", "glycan_involvement": "Glycosylation influences CRP's interaction with immune receptors.", "mechanism": "High CRP predicts increased risk of MACCEs via inflammation-mediated vascular dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "medium", "disease": "Major adverse cardiac and cerebrovascular events", "glycan_involvement": "Glycosylation may affect albumin's antioxidant and anti-inflammatory roles.", "mechanism": "Low albumin is associated with higher MACCE risk, reflecting poor nutritional/inflammatory status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Acute decompensated heart failure with diabetes", "glycan_involvement": "Both CRP and albumin are glycoproteins; glycosylation may modulate their serum levels and functions.", "mechanism": "High CAR independently predicts poor prognosis and increased MACCE risk in ADHF patients with DM.", "protein": "C-reactive protein-to-albumin ratio (CAR)", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of both proteins may influence CAR's prognostic value.", "mechanism": "CAR integrates inflammation and nutritional status, predicting adverse cardiovascular outcomes.", "protein": "C-reactive protein-to-albumin ratio (CAR)", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "medium", "disease": "Prediabetes", "glycan_involvement": "Potential modulation by glycosylation, but not directly addressed.", "mechanism": "CAR shows a trend but not a significant association with MACCEs in prediabetes.", "protein": "C-reactive protein-to-albumin ratio (CAR)", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Acute decompensated heart failure", "glycan_involvement": "Glycosylation of CRP and albumin may influence their serum levels and CAR.", "mechanism": "High CAR is associated with increased risk of MACCEs in ADHF, especially in diabetic patients.", "protein": "C-reactive protein-to-albumin ratio (CAR)", "relationship_type": "biomarker", "source_pmcid": "PMC12638916" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation, type Iy", "glycan_involvement": "Defective N-glycosylation of multiple proteins", "mechanism": "SSR4 mutations disrupt ER glycoprotein processing, leading to defective N-glycosylation.", "protein": "SSR4", "protein_enriched": { "function": "TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocati", "gene_name": "SSR1", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02315DX", "G02815KT", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G08110WX", "G08290VR", "G14260UH", "G15664MX", "G23294PN", "G23432EQ", "G23863VK", "G24954UD", "G25079LO", "G29880MM", "G30970QQ", "G31852PQ", "G35253PZ", "G39188ZX", "G39619TI", "G41247ZX", "G41840AI", "G45504EY", "G46503DX", "G46524LG", "G46902YN", "G47448YK", "G48584BU", "G49874UX", "G60967DT", "G62765YT", "G62894KT", "G64409MC", "G64527OM", "G65000LJ", "G66163OV", "G66621EA", "G70101JE", "G70619PT", "G72291OX", "G72747WU", "G77582RK", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G83633GK", "G84259QT", "G84820NF", "G84862VB", "G91392BD", "G94854LT", "G95865ZB", "G49108TO", "G37399XV", "G40206WX", "G82463GQ" ], "uniprot_id": "P43307" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation, type Ia", "glycan_involvement": "Impaired N-glycan precursor synthesis", "mechanism": "PMM2 deficiency impairs mannose metabolism, causing global N-glycosylation defects.", "protein": "PMM2", "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "high", "disease": "Muscular dystrophy, limb-girdle, autosomal recessive 23", "glycan_involvement": "Altered glycosylation affects ECM stability", "mechanism": "LAMA2 mutations affect glycosylated laminin, compromising muscle basement membrane integrity.", "protein": "LAMA2", "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Arts syndrome", "glycan_involvement": "Reduced nucleotide pools limit glycosylation", "mechanism": "PRPS1 mutations disrupt nucleotide biosynthesis, indirectly affecting glycoprotein synthesis.", "protein": "PRPS1", "protein_enriched": { "function": "Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis", "gene_name": "PRPS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60891" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Intellectual developmental disorder, X-linked syndromic, Billuart type", "glycan_involvement": "Glycosylation modulates synaptic protein trafficking", "mechanism": "OPHN1 mutations impair synaptic glycoprotein function, affecting neurodevelopment.", "protein": "OPHN1", "protein_enriched": { "function": "Core component of the SMC5-SMC6 complex, a complex involved in DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the", "gene_name": "SMC6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G53641QT" ], "uniprot_id": "Q96SB8" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Intellectual developmental disorder, X-linked 9", "glycan_involvement": "Glycosylation impacts neuronal protein stability", "mechanism": "FTSJ1 mutations affect RNA methylation and glycoprotein expression in neurons.", "protein": "FTSJ1", "protein_enriched": { "function": "Regulates ATP-dependent protein translocation into the mitochondrial matrix. Inhibits DNAJC19 stimulation of HSPA9/Mortalin ATPase activity", "gene_name": "PAM16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y3D7" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Intellectual developmental disorder with speech delay and axonal peripheral neuropathy", "glycan_involvement": "Glycosylation affects protein folding and axonal transport", "mechanism": "NEMF mutations disrupt ribosome-associated glycoprotein quality control, impairing neuronal function.", "protein": "NEMF", "protein_enriched": { "function": "3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degrada", "gene_name": "DIS3L2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8IYB7" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Joubert syndrome 17", "glycan_involvement": "Ciliary glycoprotein glycosylation is essential for signaling", "mechanism": "C5orf42 mutations affect ciliary glycoprotein function, leading to neurodevelopmental defects.", "protein": "C5orf42", "protein_enriched": { "function": "Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A bin", "gene_name": "RMI1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H9A7" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Coffin-Siris Syndrome 1", "glycan_involvement": "Glycosylation modulates chromatin-associated protein interactions", "mechanism": "ARID1B mutations disrupt chromatin remodeling and glycoprotein gene regulation.", "protein": "ARID1B", "protein_enriched": { "function": "Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry ou", "gene_name": "ARID1B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G88520YF" ], "uniprot_id": "Q8NFD5" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "medium", "disease": "Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities", "glycan_involvement": "Glycosylation influences immune cell signaling", "mechanism": "BCL11B mutations affect transcription of glycoprotein genes in neural and immune cells.", "protein": "BCL11B", "protein_enriched": { "function": "Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic sign", "gene_name": "BCL11B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9C0K0" }, "relationship_type": "causal", "source_pmcid": "PMC12639712" }, { "confidence": "high", "disease": "Influenza A virus infection (H1N1)", "glycan_involvement": "HA glycosylation modulates receptor binding and immune evasion.", "mechanism": "Lutein inhibits HA-mediated receptor binding, blocking viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "high", "disease": "Influenza A virus infection (H1N1)", "glycan_involvement": "NA cleaves sialic acids from host glycoproteins; glycosylation affects substrate accessibility.", "mechanism": "Lutein inhibits NA activity, impairing viral release.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "high", "disease": "Influenza A virus infection (H5N2)", "glycan_involvement": "Subtype-specific glycosylation influences lutein susceptibility.", "mechanism": "Lutein blocks HA-mediated entry more effectively in H5N2 than H1N1.", "protein": "Hemagglutinin (HA, H5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "high", "disease": "Influenza A virus infection (H5N2)", "glycan_involvement": "Glycosylation affects NA function and interaction with lutein.", "mechanism": "Lutein inhibits NA activity, reducing viral release in H5N2.", "protein": "Neuraminidase (NA, H5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylation is essential for viral attachment.", "mechanism": "Serve as host cell receptors for viral HA binding.", "protein": "Sialic acid-linked glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12640769" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Contains terminal sialic acids cleaved by NA.", "mechanism": "Used as substrate to measure NA activity in assays.", "protein": "Fetuin", "relationship_type": "biomarker", "source_pmcid": "PMC12640769" }, { "confidence": "medium", "disease": "Influenza B virus infection", "glycan_involvement": "Glycosylation modulates HA function.", "mechanism": "Lutein inhibits HA-mediated entry in IBV.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "medium", "disease": "Influenza B virus infection", "glycan_involvement": "Glycosylation affects NA substrate interaction.", "mechanism": "Lutein inhibits NA activity in IBV.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "low", "disease": "Influenza A virus infection", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects stability and signaling.", "mechanism": "Lutein predicted to bind IL-6, possibly modulating immune response.", "protein": "Interleukin-6", "relationship_type": "protective", "source_pmcid": "PMC12640769" }, { "confidence": "medium", "disease": "Japanese encephalitis virus infection", "glycan_involvement": "Envelope glycoprotein glycosylation critical for infectivity.", "mechanism": "Lutein shows virucidal activity against JEV, likely via envelope glycoprotein disruption.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12640769" }, { "confidence": "high", "disease": "Non-small cell lung cancer", "glycan_involvement": "N-linked glycosylation critical for ECM binding and cell adhesion.", "mechanism": "Elevated serum SPP1 correlates with tumor progression and metastasis via ECM remodeling.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation enables interaction with integrins and ECM components.", "mechanism": "SPP1-mediated ECM remodeling promotes collagen VI and decorin deposition, driving immune evasion and tumor progression.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Idiopathic pulmonary fibrosis", "glycan_involvement": "Glycosylation required for ECM binding and macrophage function.", "mechanism": "SPP1+ macrophages drive fibrosis via ECM deposition and EMT; inhibition ameliorates disease.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation mediates cell adhesion and ECM interaction.", "mechanism": "SPP1-CD44 axis accelerates lipid accumulation, EMT, and arterial remodeling.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12640834" }, { "confidence": "medium", "disease": "Abdominal aortic aneurysm", "glycan_involvement": "Glycosylation facilitates ECM remodeling.", "mechanism": "Platelet-induced SPP1 upregulation triggers inflammation and ECM degradation.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation essential for ECM deposition and cell signaling.", "mechanism": "SPP1 drives ECM remodeling, fibrosis, and muscle atrophy via systemic signaling.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12640834" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation modulates chondrocyte-ECM interactions.", "mechanism": "SPP1 overexpression activates EMT and ECM remodeling, driving cartilage degeneration.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12640834" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation influences immune cell recruitment and ECM binding.", "mechanism": "SPP1 promotes airway remodeling and inflammation, but can also reduce tissue damage in allergic asthma.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/dual (causal/protective)", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation required for integrin-mediated ECM signaling.", "mechanism": "SPP1 drives ECM reorganization, collagen crosslinking, and therapy resistance.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation enables ECM organization and cell signaling.", "mechanism": "High SPP1 marks pathological ECM remodeling, immunotherapy resistance, and poor prognosis.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12640834" }, { "confidence": "high", "disease": "Enterocolitis", "glycan_involvement": "Direct substrate; O-glycosylation of mucin is targeted.", "mechanism": "Degradation of mucin O-glycans by C. tertium enables colonization and mucosal barrier disruption.", "protein": "Mucin-type O-glycans", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Removes sialic acid from O-glycans.", "mechanism": "Cleaves terminal sialic acids from host glycoconjugates, promoting invasion and nutrient acquisition.", "protein": "Sialidase (NanH)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "high", "disease": "Inflammatory response (TLR2/4-mediated)", "glycan_involvement": "Bacterial glycoproteins/glycoconjugates act as PAMPs.", "mechanism": "Trigger TLR2/4 signaling, leading to cytokine/chemokine upregulation and inflammation.", "protein": "Cell wall glycoconjugates (PG, LTA, CPs, EXs)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "medium", "disease": "Septic arthritis", "glycan_involvement": "Binds host glycoproteins (fibronectin).", "mechanism": "Mediates adhesion to host tissues, facilitating dissemination.", "protein": "Fibronectin-binding protein (Fbp)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Targets glycosaminoglycan chains.", "mechanism": "Degrades hyaluronic acid in host tissues, aiding tissue invasion.", "protein": "Hyaluronoglucosaminidase (NagH)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Acts on O-glycosylated mucins.", "mechanism": "Removes sialic acid from mucin, exposing underlying glycans for further degradation.", "protein": "GH33 Sialidase", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "medium", "disease": "Enterocolitis", "glycan_involvement": "Recognizes specific O-glycan epitopes.", "mechanism": "Binds blood group A/B antigens on mucins, facilitating adhesion.", "protein": "CBM51/CBM32-containing protein", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "May target glycosylated host proteins.", "mechanism": "Induces cytotoxicity and disrupts epithelial barrier.", "protein": "Toxin A (TcdA)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Delivers glycan-degrading enzymes.", "mechanism": "Secretes toxins and glycosidases that degrade host barriers.", "protein": "Type II secretion system protein F (EpsF)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "low", "disease": "Hepatic abscess", "glycan_involvement": "May interact with glycosylated cell surfaces.", "mechanism": "Lyses host cells, contributing to tissue damage.", "protein": "Hemolysin (TlyA)", "relationship_type": "causal", "source_pmcid": "PMC12641198" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Changes in glycosylation (e.g., increased mannosylation) serve as cancer biomarkers.", "mechanism": "Lectin microarrays detect altered glycan patterns on cancer cell glycoproteins.", "protein": "Glycan-binding proteins (lectins, e.g., Concanavalin A)", "relationship_type": "biomarker", "source_pmcid": "PMC12641478" }, { "confidence": "medium", "disease": "Pathogen infection", "glycan_involvement": "Pathogen glycoproteins display unique glycan motifs recognized by lectins.", "mechanism": "Lectin arrays profile pathogen-specific glycan signatures.", "protein": "Glycan-binding proteins (lectins, e.g., Concanavalin A)", "relationship_type": "biomarker", "source_pmcid": "PMC12641478" }, { "confidence": "medium", "disease": "Immune response dysregulation", "glycan_involvement": "Altered glycosylation patterns reflect immune activation or suppression.", "mechanism": "Lectin microarrays characterize immune cell glycan changes.", "protein": "Glycan-binding proteins (lectins, e.g., Concanavalin A)", "relationship_type": "biomarker", "source_pmcid": "PMC12641478" }, { "confidence": "high", "disease": "Viral disease", "glycan_involvement": "SCRs recognize and bind viral N-glycans, inhibiting infection.", "mechanism": "SCRs bind N-glycans on viral envelopes, blocking viral progression.", "protein": "Synthetic Carbohydrate Receptors (SCRs, e.g., SCR019/SCR043)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641478" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Cancer cells display altered glycosylation detectable by SCRs.", "mechanism": "SCR-based microarrays detect cancer-associated glycan changes.", "protein": "Synthetic Carbohydrate Receptors (SCRs, e.g., SCR019/SCR043)", "relationship_type": "biomarker", "source_pmcid": "PMC12641478" }, { "confidence": "medium", "disease": "Pathogen infection", "glycan_involvement": "SCRs selectively bind pathogen-specific glycan motifs.", "mechanism": "SCR microarrays can profile pathogen glycan signatures.", "protein": "Synthetic Carbohydrate Receptors (SCRs, e.g., SCR019/SCR043)", "relationship_type": "biomarker", "source_pmcid": "PMC12641478" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Disrupted N-glycosylation, C- and O-mannosylation, and GPI anchor biosynthesis due to impaired mannose-1-phosphate production.", "mechanism": "Hypomorphic mutations in PMM2 reduce enzyme activity, impairing conversion of mannose-6-phosphate to mannose-1-phosphate, leading to defective glycosylation.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12641487" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Global impairment of glycoprotein biosynthesis due to insufficient mannose-1-phosphate.", "mechanism": "Loss or reduction of PMM2 activity causes multisystemic symptoms by disrupting glycosylation pathways.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12641487" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Reflects decreased glycosylation capacity in patient cells.", "mechanism": "Reduced PMM2 enzyme activity (<50%) is a diagnostic marker for PMM2-CDG.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12641487" }, { "confidence": "medium", "disease": "PMM2-CDG", "glycan_involvement": "Targeting PMM2 may restore normal glycan biosynthesis.", "mechanism": "Restoring or modulating PMM2 activity could ameliorate glycosylation defects.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641487" }, { "confidence": "high", "disease": "PMM2-CDG", "glycan_involvement": "Directly models hypo-glycosylation during early development.", "mechanism": "Acute reduction of PMM2 protein in medaka embryos recapitulates pathogenic enzyme activity levels seen in PMM2-CDG patients.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12641487" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "N-glycosylation at Asn297; galactosylation, fucosylation, sialylation changes.", "mechanism": "IgG glycosylation profile distinguishes active from latent TB; active TB shows more agalactosylation and fucosylation, latent TB more sialylation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at Asn297; fucosylation, galactosylation, sialylation, bisecting GlcNAc.", "mechanism": "Anti-S IgG1 in severe COVID-19 shows lower galactosylation/sialylation and higher bisecting GlcNAc; afucosylated IgG1 correlates with inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever", "glycan_involvement": "N-glycosylation at Asn297; fucosylation loss.", "mechanism": "Afucosylated anti-dengue IgG increases affinity for Fc\u03b3RIIIa, promoting ADE and severe disease.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation at Asn297; fucosylation, galactosylation, sialylation.", "mechanism": "HIV infection leads to higher IgG fucosylation and reduced galactosylation/sialylation, associated with lower ADCC.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation; mannosylation and sialylation changes.", "mechanism": "Severe COVID-19 patients have IgM with altered mannosylation and increased \u03b12-3 sialylation, correlating with pro-inflammatory effects and complement activation.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "medium", "disease": "Cancer (Ovarian, Breast, Colorectal, Liver)", "glycan_involvement": "N-glycosylation; unspecified sites.", "mechanism": "Aberrant N-glycosylation of IgA found in plasma of cancer patients.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation at Asn445 and Asn496.", "mechanism": "IgD glycosylation profile (increased fucosylation and mono-galactosylation) altered in multiple myeloma; potential diagnostic marker.", "protein": "IgD", "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "N-glycosylation; sialylation at multiple sites.", "mechanism": "IgE from allergic individuals has higher sialylation; sialic acid removal attenuates effector cell degranulation and anaphylaxis.", "protein": "IgE", "relationship_type": "causal", "source_pmcid": "PMC12641738" }, { "confidence": "medium", "disease": "Autoimmune Diseases (Rheumatoid Arthritis, Sj\u00f6gren\u2019s)", "glycan_involvement": "N-glycosylation in Fab variable domains.", "mechanism": "Autoantibodies in these diseases show high variable domain glycosylation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation; sialic acid with \u03b12,3-linkages.", "mechanism": "Sialylated IgA neutralizes influenza virus by mimicking cellular receptors, independent of Fab recognition.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC12641738" }, { "confidence": "high", "disease": "DMD", "glycan_involvement": "Glycosylation affects stability and bioactivity; engineered variants modify glycan-binding for improved pharmacokinetics.", "mechanism": "Inhibits myostatin/activin pathway, promoting muscle growth and reducing fibrosis.", "protein": "Follistatin", "protein_enriched": { "function": "Multifunctional regulatory protein whose primary function is to antagonize members of the transforming growth factor beta (TGF-beta) superfamily including activin, myostatin, GDF11 or bone morphogenet", "gene_name": "FST", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08146BT", "G32246SI", "G45495MK", "G52122ZD", "G57818FI", "G61937QU", "G65186XA", "G49108TO", "G64161CC", "G84452RH" ], "uniprot_id": "P19883" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "DMD", "glycan_involvement": "Catalyzes O-glycosylation of \u03b1-dystroglycan, enhancing membrane stability.", "mechanism": "GALGT2 glycosylates \u03b1-dystroglycan, stabilizing sarcolemma and upregulating utrophin, laminin, and integrin.", "protein": "GALGT2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "DMD", "glycan_involvement": "O-glycosylation is essential for ligand binding and membrane integrity.", "mechanism": "Proper glycosylation by GALGT2 enhances \u03b1-dystroglycan function, protecting muscle fibers.", "protein": "\u03b1-Dystroglycan", "relationship_type": "protective", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "DMD", "glycan_involvement": "Glycosylation may affect localization and function at neuromuscular junctions.", "mechanism": "Upregulation compensates for dystrophin loss, stabilizing muscle membrane and reducing pathology.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "medium", "disease": "DMD", "glycan_involvement": "Glycosylation influences secretion and stability.", "mechanism": "Upregulation reduces fibrosis, oxidative stress, and improves muscle/cardiac function.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "DMD", "glycan_involvement": "Interacts with glycoproteins in the DGC; glycosylation of partners is critical for complex function.", "mechanism": "Loss of dystrophin leads to membrane instability, muscle degeneration, and fibrosis.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "BMD", "glycan_involvement": "Glycosylation engineered for improved half-life and activity.", "mechanism": "Gene therapy increases muscle mass and reverses fibrosis in BMD patients.", "protein": "Follistatin", "protein_enriched": { "function": "Multifunctional regulatory protein whose primary function is to antagonize members of the transforming growth factor beta (TGF-beta) superfamily including activin, myostatin, GDF11 or bone morphogenet", "gene_name": "FST", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08146BT", "G32246SI", "G45495MK", "G52122ZD", "G57818FI", "G61937QU", "G65186XA", "G49108TO", "G64161CC", "G84452RH" ], "uniprot_id": "P19883" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "O-glycosylation of cardiac \u03b1-dystroglycan enhances function.", "mechanism": "GALGT2 overexpression prevents cardiac dysfunction in mdx mice.", "protein": "GALGT2", "relationship_type": "protective", "source_pmcid": "PMC12641824" }, { "confidence": "medium", "disease": "DMD", "glycan_involvement": "Glycosylation required for proper extracellular matrix interactions.", "mechanism": "Upregulated by GALGT2, contributing to membrane stability.", "protein": "Laminin \u03b14/\u03b15", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "medium", "disease": "DMD", "glycan_involvement": "Glycosylation affects ligand-receptor interactions.", "mechanism": "Inhibition by follistatin reduces muscle wasting and fibrosis.", "protein": "Activin/Myostatin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12641824" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "High-mannose N-glycans at G166T site mediate improved immunogenicity and stability.", "mechanism": "N-glycosylation at position 166 enhances VLP stability and uptake by antigen-presenting cells, leading to robust Th1 immune response and 100% protection in pigs.", "protein": "FMDV VP1 (G166T mutant)", "relationship_type": "protective", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "Surface N-glycans facilitate dendritic cell uptake and immune activation.", "mechanism": "Glycosylated VLPs induce stronger cellular immunity (Th1/Th2), higher CD4+/CD8+ T cell proliferation, and increased cytokine production compared to WT VLPs.", "protein": "FMDV VLP (glycosylated)", "relationship_type": "protective", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "No glycosylation; lower stability and immune activation compared to glycosylated VLPs.", "mechanism": "WT VLPs induce protective antibody responses and partial protection (80%) in pigs.", "protein": "FMDV VLP (WT)", "relationship_type": "protective", "source_pmcid": "PMC12642819" }, { "confidence": "medium", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "Glycan at 160 impairs antigenic epitope exposure.", "mechanism": "N-glycosylation at P160N reduces antibody titers and lymphocyte stimulation, likely due to masking of neutralizing epitopes.", "protein": "FMDV VP1 (P160N mutant)", "relationship_type": "protective", "source_pmcid": "PMC12642819" }, { "confidence": "medium", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "Glycan at 51 has minimal functional effect.", "mechanism": "N-glycosylation at L51T does not significantly alter immunogenicity or stability compared to WT.", "protein": "FMDV VP1 (L51T mutant)", "relationship_type": "protective", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "N-glycans act as adjuvant-like modifications.", "mechanism": "Glycosylated VLPs serve as improved vaccine candidates due to enhanced stability and immune activation.", "protein": "FMDV VLP (glycosylated)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "High-mannose N-glycans at 166 enhance vaccine efficacy.", "mechanism": "Glycosylated VP1 at G166T is a key component for next-generation VLP vaccines.", "protein": "FMDV VP1 (G166T mutant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12642819" }, { "confidence": "medium", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "N-glycan presence correlates with enhanced immune markers.", "mechanism": "Glycosylated VLPs can be used to monitor vaccine-induced immune responses.", "protein": "FMDV VLP (glycosylated)", "relationship_type": "biomarker", "source_pmcid": "PMC12642819" }, { "confidence": "medium", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "Lack of glycosylation results in lower immunogenicity.", "mechanism": "WT VP1-based VLPs serve as baseline for evaluating glycosylation effects in vaccine studies.", "protein": "FMDV VP1 (WT)", "relationship_type": "biomarker", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Foot-and-mouth disease (FMD)", "glycan_involvement": "N-glycans are essential for optimal VLP function.", "mechanism": "Glycosylation status of VLPs causally determines vaccine stability and immune response.", "protein": "FMDV VLP (glycosylated)", "relationship_type": "causal", "source_pmcid": "PMC12642819" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Increased UDP-GlcNAc production drives N-glycosylation and O-GlcNAcylation of proteins.", "mechanism": "Hyperactivation of GFAT1 increases HBP flux, leading to increased protein glycosylation, insulin resistance, and oxidative stress.", "protein": "GFAT1", "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "GLUT4 is N-glycosylated, which affects its trafficking and function.", "mechanism": "Impaired insulin signaling reduces GLUT4 translocation, decreasing glucose uptake in muscle/adipose tissue.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "IRS1 is O-GlcNAc modified, which can modulate its activity.", "mechanism": "Phosphorylation by JNK/IKK impairs IRS1 function, disrupting insulin signaling.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "high", "disease": "\u03b2-cell Dysfunction", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting its secretion and stability.", "mechanism": "Elevated IL-1\u03b2 promotes \u03b2-cell apoptosis and impairs insulin secretion.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "TNF-\u03b1 glycosylation modulates its receptor binding and activity.", "mechanism": "TNF-\u03b1 activates JNK, leading to IRS1 phosphorylation and impaired insulin signaling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "NF-\u03baB pathway components are O-GlcNAc modified, influencing transcriptional activity.", "mechanism": "NF-\u03baB activation drives pro-inflammatory gene expression in metabolic tissues.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "GLUT1 is N-glycosylated, affecting its membrane localization.", "mechanism": "M1 macrophages overexpress GLUT1 to support glycolysis and cytokine production in adipose tissue.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12643064" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "PTEN interacts with GFAT1, linking nutrient sensing to glycosylation.", "mechanism": "PTEN opposes PI3K/Akt signaling, modulating insulin sensitivity and HBP flux.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643064" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "SIRT1 activity modulates O-GlcNAcylation indirectly via AMPK and metabolic regulation.", "mechanism": "SIRT1 activation improves insulin sensitivity, reduces inflammation, and supports \u03b2-cell survival.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12643064" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Direct donor for N- and O-glycosylation of proteins.", "mechanism": "Elevated UDP-GlcNAc increases protein glycosylation, contributing to diabetic complications.", "protein": "UDP-GlcNAc", "relationship_type": "causal", "source_pmcid": "PMC12643064" }, { "confidence": "high", "disease": "Shrinking Lung Syndrome (SLS)", "glycan_involvement": "ANA are glycosylated immunoglobulins; glycosylation affects antibody function and clearance.", "mechanism": "ANA positivity is common in SLS, indicating underlying autoimmune activity.", "protein": "Anti-nuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates antibody effector functions and immune complex formation.", "mechanism": "Anti-dsDNA antibodies are specific markers for SLE diagnosis and disease activity.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation influences antibody stability and immune recognition.", "mechanism": "Anti-Smith antibodies are highly specific for SLE and support diagnosis.", "protein": "Anti-Smith antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "medium", "disease": "Mixed Connective Tissue Disease (MCTD)", "glycan_involvement": "Glycosylation affects antibody solubility and immune response.", "mechanism": "Anti-RNP antibodies are diagnostic for MCTD and may be present in SLE.", "protein": "Anti-RNP antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "medium", "disease": "Sjogren\u2019s Disease", "glycan_involvement": "Glycosylation impacts antigen-antibody interactions.", "mechanism": "Anti-Ro60 antibodies are associated with Sjogren\u2019s and SLE.", "protein": "Anti-Ro60 antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Complement proteins are glycosylated; glycosylation is essential for their function.", "mechanism": "Low complement levels indicate active SLE and immune complex deposition.", "protein": "Complement proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Shrinking Lung Syndrome (SLS)", "glycan_involvement": "Rituximab\u2019s Fc glycosylation modulates its effector functions (ADCC, CDC).", "mechanism": "Rituximab depletes B cells, reducing autoantibody production and improving lung function.", "protein": "Rituximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects ANA immunogenicity and pathogenicity.", "mechanism": "ANA positivity is a hallmark of SLE diagnosis.", "protein": "Anti-nuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation influences antibody function.", "mechanism": "Anti-RNP antibodies may be present in SLE and indicate overlap syndromes.", "protein": "Anti-RNP antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fc glycosylation is critical for rituximab\u2019s therapeutic efficacy.", "mechanism": "Rituximab is used off-label for refractory SLE manifestations.", "protein": "Rituximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643461" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation (reduced GlcNAc and GalNAc, and MGAT5 expression, impact ICOS surface expression)", "mechanism": "ICOS expression on Tfh cells is required for their helper function and autoantibody production; glutaminolysis supports ICOS expression.", "protein": "ICOS", "protein_enriched": { "function": "Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response (PubMed:9930702). Upon binding to its ligand ICOSL expressed on antigen p", "gene_name": "ICOS", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "Q9Y6W8" }, "relationship_type": "causal", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation likely impacts OX-40 function (not directly shown but inferred from global N-glycan changes)", "mechanism": "OX-40 expression on Tfh cells is required for their maintenance and function; reduced by glutaminolysis inhibition.", "protein": "OX-40 (TNFRSF4)", "relationship_type": "causal", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Directly catalyzes N-glycan branching (GlcNAc-b-1,6)", "mechanism": "MGAT5-mediated N-glycan branching enhances T cell proliferation; reduced by glutaminolysis inhibition, potentially limiting Tfh expansion.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "GLUT1 is N-glycosylated, which affects its trafficking and function", "mechanism": "GLUT1 expression supports glycolysis in Tfh cells; reduced by glutaminolysis inhibition, limiting Tfh function.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC12643493" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Indirect\u2014GLS1 activity supports glycan precursor synthesis (GlcNAc, GalNAc)", "mechanism": "GLS1 activity supports glutaminolysis in Tfh cells, promoting autoimmunity; inhibition reduces autoantibody production.", "protein": "GLS1", "protein_enriched": { "function": "Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, th", "gene_name": "GLS", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G27947YN", "G36670VW", "G52527GH", "G66760KM", "G83646BJ", "G91473PK", "G49108TO" ], "uniprot_id": "O94925" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "N-glycosylation modulates PD-1 stability and function (not directly tested here)", "mechanism": "PD-1 is upregulated on lupus Tfh cells, sustaining their numbers and B cell help.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Not directly discussed", "mechanism": "BCL-6 expression in Tfh cells is required for their differentiation; reduced by glutaminolysis inhibition.", "protein": "BCL-6", "relationship_type": "causal", "source_pmcid": "PMC12643493" }, { "confidence": "low", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "CD19 is a glycoprotein; glycosylation affects B cell signaling", "mechanism": "CD19+ B cells are expanded in lupus and contribute to autoantibody production.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "GL7 is a sialylated glycan epitope", "mechanism": "GL7 marks activated/GC B cells, which are expanded in lupus and reduced by glutaminolysis inhibition.", "protein": "GL7 epitope", "relationship_type": "biomarker", "source_pmcid": "PMC12643493" }, { "confidence": "medium", "disease": "Chronic Graft Versus Host Disease (cGVHD)", "glycan_involvement": "N-glycosylation (as above)", "mechanism": "ICOS expression on Tfh cells is required for extrafollicular B cell help and autoantibody production; reduced by glutaminolysis inhibition.", "protein": "ICOS", "protein_enriched": { "function": "Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response (PubMed:9930702). Upon binding to its ligand ICOSL expressed on antigen p", "gene_name": "ICOS", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "Q9Y6W8" }, "relationship_type": "causal", "source_pmcid": "PMC12643493" }, { "confidence": "high", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Essential for ECM structure and glycan-mediated cell adhesion.", "mechanism": "Loss due to LAMA2 mutations disrupts muscle cell adhesion, leading to muscle degeneration.", "protein": "Laminin-211/221 (Laminin-\u03b12)", "relationship_type": "causal", "source_pmcid": "PMC12643501" }, { "confidence": "high", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Glycosylation critical for ECM integration and receptor binding.", "mechanism": "Recombinant human laminin-111 restores adhesion signaling, improves muscle strength, and reduces disease progression.", "protein": "Laminin-111", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643501" }, { "confidence": "high", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Highly O-glycosylated; glycan chains mediate laminin binding.", "mechanism": "Mislocalization and reduced function due to loss of laminin-211/221; essential for sarcolemmal stability.", "protein": "\u03b1-Dystroglycan (\u03b1DG)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12643501" }, { "confidence": "high", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "N-glycosylation required for integrin activation and ECM binding.", "mechanism": "Inactive and mislocalized in LAMA2-CMD; restored by rhLAM-111, reactivating downstream signaling.", "protein": "Integrin \u03b17\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12643501" }, { "confidence": "medium", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Glycosylation affects stability and trafficking.", "mechanism": "Downregulated and mislocalized in early disease; restoration supports muscle regeneration and proteostasis.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12643501" }, { "confidence": "medium", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Glycosylation may regulate cytoskeletal interactions.", "mechanism": "Early loss impairs stress response and muscle repair; restored localization after rhLAM-111.", "protein": "Heat Shock Protein 27 (HSP27)", "protein_enriched": { "function": "Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state (PubMed:10383393, PubMed:20178975). Plays a role in stress resist", "gene_name": "HSPB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04792" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12643501" }, { "confidence": "high", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "N-glycosylation required for membrane trafficking and function.", "mechanism": "Downregulated and mislocalized in LAMA2-CMD; restored by rhLAM-111, improving glycolysis and reducing ROS.", "protein": "Glucose Transporter 1 (GLUT1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12643501" }, { "confidence": "medium", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Glycosylation modulates membrane localization.", "mechanism": "Downregulated in LAMA2-CMD; involved in GLUT1 and IGF1R trafficking.", "protein": "Caveolin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the re", "gene_name": "Cav1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49817" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12643501" }, { "confidence": "medium", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "Downregulated in LAMA2-CMD; restoration improves muscle regeneration and glycolysis.", "protein": "Insulin-like Growth Factor 1 Receptor (IGF1R)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12643501" }, { "confidence": "medium", "disease": "Laminin-\u03b12\u2013related congenital muscular dystrophy (LAMA2-CMD)", "glycan_involvement": "Glycosylation may affect membrane association.", "mechanism": "Mislocalized in LAMA2-CMD; restored to normal distribution by rhLAM-111.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "biomarker/compensatory", "source_pmcid": "PMC12643501" }, { "confidence": "high", "disease": "ICI-DM", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and ligand binding.", "mechanism": "Blockade of PD-1 disrupts immune tolerance, leading to T-cell-mediated pancreatic \u03b2-cell destruction.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "high", "disease": "ICI-DM", "glycan_involvement": "PD-L1 glycosylation modulates immune recognition and therapeutic antibody binding.", "mechanism": "PD-L1 blockade enhances cytotoxic T-cell activity, promoting \u03b2-cell destruction.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "high", "disease": "FT1D", "glycan_involvement": "As a therapeutic antibody, glycosylation affects tislelizumab's efficacy and half-life.", "mechanism": "Tislelizumab (anti-PD-1 antibody) therapy triggers rapid-onset \u03b2-cell destruction and insulin deficiency.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "medium", "disease": "FT1D", "glycan_involvement": "Glycosylation of PD-1 influences its immune regulatory function.", "mechanism": "PD-1 inhibition leads to loss of immune tolerance and acute \u03b2-cell failure.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "medium", "disease": "FT1D", "glycan_involvement": "PD-L1 glycosylation is critical for immune checkpoint function.", "mechanism": "PD-L1 pathway disruption by ICIs accelerates \u03b2-cell destruction.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "medium", "disease": "DKA", "glycan_involvement": "Therapeutic antibody glycosylation impacts pharmacodynamics.", "mechanism": "Tislelizumab-induced \u03b2-cell loss leads to insulin deficiency and DKA.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12643655" }, { "confidence": "high", "disease": "Lung squamous cell carcinoma", "glycan_involvement": "Glycosylation may affect PD-1 antibody binding.", "mechanism": "PD-1 is targeted by tislelizumab to enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643655" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation", "mechanism": "N-glycosylation at N221/N292 promotes lymph node metastasis and is detectable in serum", "protein": "Cathepsin V", "relationship_type": "biomarker", "source_pmcid": "PMC12643890" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "O-glycosylation", "mechanism": "Aberrant O-glycosylation drives immune evasion and matrix remodeling", "protein": "Mucin (MUC5AC)", "relationship_type": "causal", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation", "mechanism": "Disease-specific N-glycosylation patterns discriminate lung cancer from controls", "protein": "Haptoglobin beta chain", "relationship_type": "biomarker", "source_pmcid": "PMC12643890" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation", "mechanism": "Glycosylation stabilizes PD-L1 and inhibits T-cell function, mediating immune checkpoint resistance", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation", "mechanism": "N-glycosylation at Asn291 stabilizes TIM-4, enhancing cell motility", "protein": "TIM-4", "protein_enriched": { "function": "Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation. Controls T-cell activation in a bimodal fashion, decreasing th", "gene_name": "TIMD4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q96H15" }, "relationship_type": "causal", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation", "mechanism": "N-glycosylation at Asn134 enables GPNMB-EGFR interaction, promoting progression", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "O-glycosylation", "mechanism": "GALNT-mediated O-glycosylation co-activates PI3K/AKT and MAPK/ERK pathways, driving malignancy", "protein": "ITGA5 (Integrin alpha-5)", "relationship_type": "causal", "source_pmcid": "PMC12643890" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "N-glycosylation", "mechanism": "Elevated B4GALT2 expression correlates with poor survival and CD8+ T-cell exclusion", "protein": "B4GALT2", "protein_enriched": { "function": "Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts", "gene_name": "B4GALT7", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBV7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation stabilizes SMAD4, enhancing TGF-\u03b2 signaling and promoting EMT/metastasis", "protein": "SMAD4", "protein_enriched": { "function": "In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 rele", "gene_name": "SMAD4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13485" }, "relationship_type": "causal", "source_pmcid": "PMC12643890" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation", "mechanism": "GPNMB-mediated N-glycosylation facilitates EGFR interaction, driving proliferation and progression", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12643890" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Changes in N-glycan composition and abundance serve as disease markers.", "mechanism": "Altered glycosylation patterns in plasma N-glycans are associated with diabetes pathogenesis and progression.", "protein": "Plasma glycoproteins", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12644503" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Specific N-glycan structures are altered in cancer and can be used for diagnosis or targeted therapy.", "mechanism": "Dysregulated N-glycosylation affects cell signaling, adhesion, and immune evasion in cancer.", "protein": "Plasma glycoproteins", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12644503" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "N-glycan changes in plasma proteins are potential biomarkers for Alzheimer\u2019s.", "mechanism": "Altered plasma glycan profiles reflect neurodegenerative changes.", "protein": "Plasma glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12644503" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Altered N-glycan patterns in plasma proteins.", "mechanism": "Changes in glycosylation may reflect neurodegenerative processes.", "protein": "Plasma glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12644503" }, { "confidence": "high", "disease": "Mucopolysaccharidosis", "glycan_involvement": "Quantitative and qualitative changes in urinary GAGs are diagnostic for mucopolysaccharidosis.", "mechanism": "Defective degradation of GAGs leads to their accumulation and excretion in urine.", "protein": "Urinary glycosaminoglycans (GAGs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12644503" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-glycan composition changes serve as potential cancer biomarkers.", "mechanism": "Altered O-glycosylation in keratinocytes is associated with malignant transformation.", "protein": "Keratinocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12644503" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Targeting specific glycan structures may offer therapeutic benefit.", "mechanism": "Aberrant glycosylation modulates immune recognition and metastasis.", "protein": "Plasma glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12644503" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "N-glycan abundance and structure changes are measurable in plasma.", "mechanism": "Glycan profile shifts correlate with disease state.", "protein": "Plasma glycoproteins", "relationship_type": "diagnostic_marker", "source_pmcid": "PMC12644503" }, { "confidence": "high", "disease": "Mucopolysaccharidosis", "glycan_involvement": "Specific GAG-derived oligosaccharides are detected in urine.", "mechanism": "Elevated urinary GAGs indicate lysosomal storage dysfunction.", "protein": "Urinary glycosaminoglycans (GAGs)", "relationship_type": "diagnostic_marker", "source_pmcid": "PMC12644503" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered sialic acid and fucose content in N-glycans.", "mechanism": "Sialylation and fucosylation changes are linked to tumor progression.", "protein": "Plasma glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12644503" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Chondroitin sulfate glycosylation critical for ECM structure and function.", "mechanism": "Aggrecan forms ECM barriers restricting tau internalization and spread; its disruption facilitates tau propagation.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "causal", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Chondroitin sulfate glycosylation modulates ECM properties.", "mechanism": "Upregulated versican expression alters ECM, promoting increased extracellular diffusion and tau spread.", "protein": "Versican", "protein_enriched": { "function": "May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "causal", "source_pmcid": "PMC12644816" }, { "confidence": "high", "disease": "Tauopathy", "glycan_involvement": "Heparan sulfate glycosylation enables tau binding and uptake.", "mechanism": "HSPGs mediate tau internalization and propagation in tauopathy models.", "protein": "Heparan sulfate proteoglycans (HSPGs)", "relationship_type": "causal", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Removes sulfate groups from glycosaminoglycans, altering ECM composition.", "mechanism": "Upregulation of GALNS enhances degradation of sulfated GAGs, disrupting ECM and facilitating tau spread.", "protein": "N-acetylgalactosamine 6-sulfatase (GALNS)", "protein_enriched": { "function": "", "gene_name": "GALNS", "glycan_count": 33, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01937VC", "G02815KT", "G05724UK", "G06110VR", "G14669DU", "G28681TP", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G74724QE", "G92050GC", "G92275SC", "G00912UN", "G05049YU", "G14972EH", "G15664MX", "G40574BA", "G43223CG", "G47702MW", "G49018RC", "G49589RB", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G81124ET", "G83460ZZ", "G85554PZ", "G87661QW", "G88891KO", "G90659AW", "G95177YH" ], "uniprot_id": "P34059" }, "relationship_type": "causal", "source_pmcid": "PMC12644816" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau can be O-glycosylated, affecting aggregation and pathology.", "mechanism": "Extracellular tau seeds induce neurodegeneration, inflammation, and ECM disruption.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Heavily glycosylated; glycosylation required for lysosomal targeting.", "mechanism": "LAMP-1 surrounds apoptotic debris in tau pathology, indicating lysosomal involvement.", "protein": "LAMP-1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:15121881). Acts as an important regulator o", "gene_name": "Lamp1", "glycan_count": 39, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G65414LI", "G05724UK", "G06110VR", "G14669DU", "G33609NS", "G39188ZX", "G48584BU", "G51672OH", "G64527OM", "G66538GV", "G02815KT", "G23863VK", "G25637MV", "G74724QE", "G82119TF", "G47012YE", "G53677UQ", "G93413PK", "G56940FB", "G26436YP", "G10773YW", "G29898ES", "G41840AI", "G50282JC", "G05962QB", "G11314AS", "G57776ZU", "G93067EQ", "G10039CR", "G39368QD", "G39643OJ", "G65540UB", "G66621EA", "G73585DO", "G76329HL", "G76915KR", "G79896BV", "G62765YT", "G49108TO" ], "uniprot_id": "P11438" }, "relationship_type": "biomarker", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Gliosis", "glycan_involvement": "Glycosylation may affect filament assembly and astrocyte function.", "mechanism": "GFAP-positive astrocytes internalize ECM glycoproteins (aggrecan) during tau-induced gliosis.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Tauopathy", "glycan_involvement": "Glycosylation modulates protease activity and ECM interaction.", "mechanism": "Adamts4 deletion reduces ECM remodeling, tau spread, and neurodegeneration.", "protein": "Adamts4", "protein_enriched": { "function": "Cleaves aggrecan, a cartilage proteoglycan, at the '392-Glu-|-Ala-393' site and may be involved in its turnover (PubMed:10356395, PubMed:10827174). Also cleaves COMP (PubMed:39672391). May play an imp", "gene_name": "ADAMTS4", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G83460ZZ", "G29068FM", "G43417UB" ], "uniprot_id": "O75173" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12644816" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Upregulated IL-6 indicates inflammatory response in tau pathology.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12644816" }, { "confidence": "low", "disease": "Apoptosis", "glycan_involvement": "Glycosylation may regulate activation and localization.", "mechanism": "Increased caspase-3 expression marks apoptosis in tau-induced neurodegeneration.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12644816" }, { "confidence": "high", "disease": "Phosphoglucomutase 1 deficiency (PGM1-CDG)", "glycan_involvement": "Defective N- and O-glycosylation due to impaired glucose-1-phosphate metabolism.", "mechanism": "PGM1 deficiency impairs glycosylation, leading to multisystem disease including cardiac involvement.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "high", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Impaired glycosylation of cardiac structural and signaling proteins.", "mechanism": "PGM1-CDG patients frequently develop early-onset dilated cardiomyopathy due to glycosylation defects affecting cardiac proteins.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Global glycoprotein hypoglycosylation impairs cardiac function.", "mechanism": "PGM1-CDG leads to cardiac dysfunction and heart failure via glycosylation defects.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Atrial septal defect (ASD)", "glycan_involvement": "Defective glycosylation during cardiac development.", "mechanism": "PGM1-CDG is associated with increased risk of congenital heart defects including ASD.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Growth retardation", "glycan_involvement": "Impaired glycosylation of growth factor receptors and hormones.", "mechanism": "PGM1-CDG causes growth retardation due to multisystem glycosylation defects.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Recurrent hypoglycaemia", "glycan_involvement": "Defective glycosylation of metabolic enzymes.", "mechanism": "PGM1-CDG disrupts glucose metabolism and glycosylation, leading to hypoglycaemia.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Myocarditis (Parvovirus B19)", "glycan_involvement": "IgG glycosylation affects its anti-inflammatory and immunomodulatory properties.", "mechanism": "IgG administered as immunotherapy to treat viral myocarditis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Coagulation disorders", "glycan_involvement": "Impaired glycosylation of coagulation glycoproteins.", "mechanism": "PGM1-CDG patients may develop coagulation disorders due to glycosylation defects in clotting factors.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "low", "disease": "Hepatic congestion", "glycan_involvement": "Indirect effect via cardiac glycoprotein defects.", "mechanism": "PGM1-CDG can cause hepatic congestion secondary to cardiac dysfunction.", "protein": "Phosphoglucomutase 1 (PGM1)", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "medium", "disease": "Myocarditis (Parvovirus B19)", "glycan_involvement": "Viral glycoproteins interact with host glycan receptors.", "mechanism": "Parvovirus B19 infection triggers myocarditis.", "protein": "Parvovirus B19 capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12644980" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "N-glycosylation critical for ICAM-1 function and leukocyte binding.", "mechanism": "ICAM-1 upregulation mediates leukocyte adhesion and infiltration, contributing to neuroinflammation and BBB disruption; EVs reduce ICAM-1 expression, decreasing injury.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12645355" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "N-glycosylation modulates VCAM-1 adhesive properties.", "mechanism": "VCAM-1 upregulation on endothelium promotes leukocyte adhesion and neuroinflammation; EVs modulate VCAM-1 to protect BBB.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12645355" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation affects EV surface recognition and biodistribution.", "mechanism": "CD9 is a tetraspanin marker on EVs, facilitating targeting and uptake by neural cells.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12645355" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation modulates EV-cell interactions.", "mechanism": "CD63 on EVs mediates interaction with recipient cells, influencing therapeutic delivery.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12645355" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation may affect EV targeting.", "mechanism": "CD81 facilitates EV uptake by neural and endothelial cells, enhancing neuroprotection.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12645355" }, { "confidence": "high", "disease": "Neural degeneration", "glycan_involvement": "N-glycosylation required for BDNF secretion and stability.", "mechanism": "EVs engineered to carry BDNF promote neural survival and repair via TrkB signaling.", "protein": "BDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12645355" }, { "confidence": "high", "disease": "Angiogenesis impairment", "glycan_involvement": "N-glycosylation essential for VEGF receptor binding.", "mechanism": "EVs deliver VEGF to promote angiogenesis and vascular repair post-stroke.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12645355" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for TGF-\u03b21 secretion and activity.", "mechanism": "Microglia-derived EVs enriched in TGF-\u03b21 activate Smad2/3 signaling, reducing inflammation and promoting angiogenesis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective", "source_pmcid": "PMC12645355" }, { "confidence": "medium", "disease": "Blood-brain barrier disruption", "glycan_involvement": "Glycosylation may affect HSP27 stability and function.", "mechanism": "EVs with HSP27 improve ATP production and tight junction integrity, preserving BBB function.", "protein": "HSP27", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12645355" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation of RVG critical for receptor binding and targeting.", "mechanism": "RVG29-functionalized EVs target neural tissue, enhancing delivery of neuroprotective peptides and RNAs.", "protein": "Rabies virus glycoprotein (RVG29)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12645355" }, { "confidence": "high", "disease": "Influenza B virus infection", "glycan_involvement": "N-glycosylation at HA residue 196 regulates receptor binding specificity.", "mechanism": "HA mediates viral entry by binding sialic acid receptors on host glycoproteins.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Severe influenza B (lower respiratory/GI involvement)", "glycan_involvement": "Mutation abolishing N-glycosylation at 196 enables dual \u03b12,6/\u03b12,3 sialic acid binding.", "mechanism": "Loss of N-glycosylation at HA 196 expands binding to \u03b12,3-linked sialic acids, increasing tropism for lower respiratory and GI tract.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Age-specific influenza B susceptibility", "glycan_involvement": "Glycosylation status at 196 modulates age-related host tropism.", "mechanism": "Victoria lineage HA with loss of N-glycosylation at 196 binds \u03b12,3-sialosides, prevalent in children\u2019s upper respiratory tract.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Influenza B virus infection", "glycan_involvement": "Presence of N-glycan at 196 restricts receptor specificity.", "mechanism": "Yamagata lineage HA retains N-glycosylation at 196, restricting binding to \u03b12,6-sialosides, limiting tropism.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Influenza B virus infection", "glycan_involvement": "Loss of N-glycosylation at 196 correlates with epidemiologic success.", "mechanism": "Victoria lineage viruses with N196 mutations (e.g., N196K, N196D) show increased endemic activity and fitness.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "medium", "disease": "Influenza B virus infection", "glycan_involvement": "Conserved N-glycosylation at 196 limits adaptability.", "mechanism": "Yamagata lineage extinction may be linked to lack of N196 mutations and restricted receptor binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "medium", "disease": "Influenza B virus infection", "glycan_involvement": "Experimental loss of N-glycosylation at 196 increases \u03b12,3 binding.", "mechanism": "Egg-adaptive mutations at HA 194\u2013196 alter N-glycosylation, artificially expanding \u03b12,3 binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "medium", "disease": "Influenza B virus infection", "glycan_involvement": "Preference for \u03b12,6-sialosides on extended LacNAc structures at \u03b11,3-antenna.", "mechanism": "Glycan topology (length and antenna position) influences HA binding and host adaptation.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Influenza B virus infection", "glycan_involvement": "N-glycan at 196 physically obstructs \u03b12,3-sialoside binding.", "mechanism": "N-glycosylation at 196 creates steric hindrance, favoring \u03b12,6 over \u03b12,3 sialic acid binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Influenza B virus infection", "glycan_involvement": "Loss of N-glycan at 196 equalizes hydrogen-bonding networks for both sialoside types.", "mechanism": "Mutations abolishing N-glycosylation at 196 enable hydrogen bonding with both \u03b12,3 and \u03b12,6 sialosides.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12645935" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation is essential for utrophin's membrane localization and function.", "mechanism": "Upregulation and membrane localization of utrophin stabilizes sarcolemma and compensates for dystrophin loss.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Heavily glycosylated; glycosylation required for interaction with ECM and dystrophin-associated complex.", "mechanism": "Obestatin increases \u03b2-dystroglycan expression, supporting sarcolemma stability.", "protein": "\u03b2-dystroglycan", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Z1E9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation modulates integrin function and cell-matrix interactions.", "mechanism": "Obestatin upregulates \u03b17-integrin, enhancing muscle fiber adhesion and repair.", "protein": "\u03b17-integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may affect complex assembly and stability.", "mechanism": "Obestatin increases \u03b1-syntrophin, supporting the utrophin glycoprotein complex and sarcolemma integrity.", "protein": "\u03b1-syntrophin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation critical for integrin-mediated adhesion.", "mechanism": "PPP3 knockdown reduces \u03b21D-integrin, implicating its role in muscle repair.", "protein": "\u03b21D-integrin", "protein_enriched": { "function": "Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane pr", "gene_name": "FLNB", "glycan_count": 10, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G30970QQ", "G49642SA", "G49108TO", "G95177YH", "G62765YT", "G06247RL", "G40926MX", "G47518TP", "G59536GA", "G80920RR" ], "uniprot_id": "O75369" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Heavily glycosylated; glycosylation required for lysosomal targeting and function.", "mechanism": "LAMP2 levels reflect autophagic flux; obestatin reduces LAMP2-positive inclusions, indicating improved autophagy.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, 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"G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "biomarker", "source_pmcid": "PMC12647412" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may affect localization and stability.", "mechanism": "PPP3 knockdown reduces NOS1, which is involved in muscle signaling and repair.", "protein": "NOS1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "medium", "disease": "Skeletal muscle myopathies", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and signaling.", "mechanism": "Obestatin transactivates EGFR via GPR39/\u03b2-arrestin, promoting myogenic differentiation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647412" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Extensively glycosylated; glycosylation critical for ECM interactions.", "mechanism": "Laminin is used as a marker for sarcolemma integrity; its interaction with glycoprotein complexes is essential for muscle stability.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12647412" }, { "confidence": "low", "disease": "Skeletal muscle myopathies", "glycan_involvement": "N-glycosylation required for receptor stability and function.", "mechanism": "TFRC is used as a mitochondrial marker; altered expression reflects mitochondrial dysfunction in muscle disease.", "protein": "Transferrin receptor (TFRC)", "relationship_type": "biomarker", "source_pmcid": "PMC12647412" }, { "confidence": "high", "disease": "Inflammatory disorders", "glycan_involvement": "LacdiNAc motif on milk oligosaccharides directly alters immune cell signaling", "mechanism": "Modulates cytokine production in macrophages (upregulates IL-10, CCL17; downregulates IL-12p40, IL-1\u03b2, IL-23)", "protein": "LacdiNAc (GalNAc\u03b21-4GlcNAc)", "relationship_type": "immunomodulatory/protective", "source_pmcid": "PMC12647773" }, { "confidence": "high", "disease": "Bacterial infection (biofilm-associated)", "glycan_involvement": "Free LacdiNAc motif acts as anti-biofilm agent", "mechanism": "Inhibits biofilm formation by S. aureus and S. agalactiae", "protein": "LacdiNAc (GalNAc\u03b21-4GlcNAc)", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Viral infection (influenza, coronavirus)", "glycan_involvement": "Sulfation increases anti-viral potency of 2'-FL", "mechanism": "Enhanced binding to viral proteins, suggesting decoy receptor function", "protein": "6S-2'-fucosyllactose (sulfated 2'-FL)", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Oxidative stress-related disorders", "glycan_involvement": "Sulfated glycan structures act as antioxidants", "mechanism": "Potentially mitigates oxidative stress during increased lipid catabolism", "protein": "Keratan sulfate-like oligosaccharides", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Pathogen colonization (general)", "glycan_involvement": "Fucosylated motif mimics host cell receptors", "mechanism": "Acts as soluble decoy receptor for pathogens", "protein": "Type-2 H antigen (Fuc\u03b11-2Gal\u03b21-4GlcNAc)", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Immune immaturity in neonates", "glycan_involvement": "Sialylation of H antigen enhances immune signaling", "mechanism": "Binds Siglec-1 and Siglec-15, suggesting immune modulation", "protein": "Distal type-2 sialyl-H antigen", "relationship_type": "immunomodulatory/protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Bacterial infection (biofilm-associated)", "glycan_involvement": "Glucuronylation confers anti-biofilm activity", "mechanism": "Inhibits biofilm formation by K. pneumoniae and S. aureus", "protein": "Glucuronyl-lactose", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Intestinal dysbiosis", "glycan_involvement": "Extended poly-LacNAc chains serve as substrates for commensal bacteria", "mechanism": "Supports selection for beneficial microbiota", "protein": "Poly-LacNAc (Gal\u03b21-4GlcNAc)n", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "medium", "disease": "Pathogen colonization (general)", "glycan_involvement": "Sialylated motif blocks pathogen binding", "mechanism": "Known to inhibit pathogen adhesion", "protein": "Sialyl-Lewis X", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "Fucosylated motif present in anti-biofilm active MOs", "mechanism": "Associated with late-stage milk oligosaccharides that may inhibit biofilm formation", "protein": "Lewis Y antigen", "relationship_type": "protective", "source_pmcid": "PMC12647773" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "MFG-E8 is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Serum MFG-E8 levels are significantly lower in KD patients, especially those with CALs, compared to controls; useful for diagnosis.", "protein": "MFG-E8", "relationship_type": "biomarker", "source_pmcid": "PMC12647962" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may influence MFG-E8's interaction with phagocytes and apoptotic cells.", "mechanism": "Exogenous MFG-E8 administration alleviates coronary artery inflammation and reduces endothelial cell pyroptosis in murine KD model.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "high", "disease": "Coronary artery lesions (CALs)", "glycan_involvement": "Glycosylation status may affect circulating levels and tissue targeting.", "mechanism": "Lower serum MFG-E8 correlates with presence and severity of CALs in KD patients.", "protein": "MFG-E8", "relationship_type": "biomarker", "source_pmcid": "PMC12647962" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may modulate anti-oxidative and anti-inflammatory functions.", "mechanism": "MFG-E8 supplementation reduces oxidative stress and endothelial injury in KD models.", "protein": "MFG-E8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12647962" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may affect receptor binding and anti-pyroptotic activity.", "mechanism": "MFG-E8 inhibits NLRP3 inflammasome activation and endothelial cell pyroptosis.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may influence detectability in serum assays.", "mechanism": "Combining MFG-E8 with Fbg and TT improves diagnostic accuracy for KD.", "protein": "MFG-E8", "relationship_type": "biomarker", "source_pmcid": "PMC12647962" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may affect chemokine interactions and immune modulation.", "mechanism": "MFG-E8 reduces neutrophil infiltration and vascular inflammation in KD mouse model.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may impact anti-oxidative properties.", "mechanism": "MFG-E8 ameliorates oxidative stress imbalance in endothelial cells exposed to KD serum.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may influence cell adhesion and signaling.", "mechanism": "MFG-E8 reduces expression of VCAM-1, indicating protection against endothelial activation.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "low", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation may modulate receptor interactions and downstream signaling.", "mechanism": "MFG-E8 may promote tissue repair and regeneration via PKC and VEGF-Akt pathways.", "protein": "MFG-E8", "relationship_type": "protective", "source_pmcid": "PMC12647962" }, { "confidence": "high", "disease": "inflammation", "glycan_involvement": "Glycosylation modulates its plasma half-life and immunomodulatory function.", "mechanism": "Elevated levels indicate systemic inflammation.", "protein": "\u03b1-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "inflammation", "glycan_involvement": "Glycosylation affects its solubility and immune recognition.", "mechanism": "Acute-phase reactant; elevated in inflammatory states.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "anemia", "glycan_involvement": "Glycosylation is essential for receptor stability and function.", "mechanism": "Elevated sTfR reflects increased erythropoiesis and iron deficiency.", "protein": "soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "medium", "disease": "beriberi", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Low activity indicates thiamine deficiency, which can cause beriberi.", "protein": "erythrocyte transketolase", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "medium", "disease": "riboflavin deficiency", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "High activity coefficient indicates riboflavin deficiency.", "protein": "erythrocyte glutathione reductase", "protein_enriched": { "function": "Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH). Constitutes the major mechanism to maintain a high GSH:GSSG ratio in the cytosol", "gene_name": "GSR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00390" }, "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "macrocytic anemia", "glycan_involvement": "Glycosylation required for stability and receptor binding.", "mechanism": "Low holoTC reflects vitamin B12 deficiency, leading to macrocytic anemia.", "protein": "holo transcobalamin", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "anemia", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Low ferritin indicates iron deficiency anemia.", "protein": "ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "medium", "disease": "thyroid dysfunction", "glycan_involvement": "N-glycosylation critical for hormone precursor function.", "mechanism": "Elevated thyroglobulin can indicate thyroid dysfunction.", "protein": "thyroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "microcytic anemia", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Elevated sTfR associated with microcytic anemia due to iron deficiency.", "protein": "soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "anemia", "glycan_involvement": "Glycosylation modulates its immunological role.", "mechanism": "Used to adjust ferritin for inflammation in anemia diagnosis.", "protein": "\u03b1-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12648943" }, { "confidence": "high", "disease": "Peripheral T-cell lymphoma (PTCL)", "glycan_involvement": "AAG is heavily N-glycosylated, which influences its binding properties.", "mechanism": "AAG levels are elevated in PTCL patients and affect total valemetostat exposure by binding the drug in plasma.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12649291" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "N-glycosylation of AAG affects its drug-binding capacity.", "mechanism": "AAG levels are elevated in ATLL patients and modulate total valemetostat exposure.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Non-Hodgkin lymphoma (NHL)", "glycan_involvement": "N-glycosylation modulates AAG's plasma binding properties.", "mechanism": "AAG levels are higher in NHL patients, impacting pharmacokinetics of drugs like valemetostat.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma (PTCL)", "glycan_involvement": "P-gp is N-glycosylated, affecting its localization and function.", "mechanism": "P-gp inhibitors increase valemetostat exposure in PTCL patients by reducing drug efflux.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic target/modulator", "source_pmcid": "PMC12649291" }, { "confidence": "high", "disease": "Peripheral T-cell lymphoma (PTCL)", "glycan_involvement": "Indirect; EZH2 activity may influence glycosylation patterns via epigenetic regulation.", "mechanism": "EZH2 is overexpressed or mutated in PTCL, driving malignancy; targeted by valemetostat.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma (PTCL)", "glycan_involvement": "Indirect; possible epigenetic effects on glycosylation.", "mechanism": "EZH1 is overexpressed in PTCL and targeted by valemetostat.", "protein": "EZH1", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-,", "gene_name": "EZH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92800" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation affects AAG's drug-binding and clearance.", "mechanism": "High AAG levels increase total valemetostat exposure, potentially modulating risk of thrombocytopenia.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "modulator", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation impacts AAG's interaction with drugs.", "mechanism": "Elevated AAG may alter valemetostat pharmacokinetics, influencing anemia risk.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "modulator", "source_pmcid": "PMC12649291" }, { "confidence": "low", "disease": "Neutropenia", "glycan_involvement": "N-glycosylation modulates AAG's function.", "mechanism": "AAG levels may affect drug exposure and neutropenia risk, though relationship is less clear.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "modulator", "source_pmcid": "PMC12649291" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "N-glycosylation affects P-gp's drug transport activity.", "mechanism": "P-gp inhibitors increase valemetostat exposure in ATLL patients.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic target/modulator", "source_pmcid": "PMC12649291" }, { "confidence": "high", "disease": "Nephrolithiasis (NL)", "glycan_involvement": "N-glycosylation affects stability and renal handling.", "mechanism": "Elevated urinary excretion in NL patients and their children; correlates with urinary supersaturation; reflects tubular inflammation and injury.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "high", "disease": "Nephrolithiasis (NL)", "glycan_involvement": "N-glycosylation critical for renal reabsorption and function.", "mechanism": "Elevated urinary excretion in NL patients and their children; correlates with urinary supersaturation; reflects tubular injury and impaired reabsorption.", "protein": "Transferrin (TF)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Nephrolithiasis (NL)", "glycan_involvement": "N-glycosylation modulates renal filtration and anti-crystallization activity.", "mechanism": "Elevated in NL and high-risk children; inhibits calcium oxalate crystallization and acts as a radical scavenger.", "protein": "Alpha-1-microglobulin/bikunin precursor (AMBP)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Nephrolithiasis (NL)", "glycan_involvement": "N-glycosylation required for mineral binding and inhibitory function.", "mechanism": "Elevated in high-risk children; binds calcium and phosphate, inhibits crystallization; associated with tubular injury.", "protein": "Alpha-2-HS-glycoprotein (Fetuin-A)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "low", "disease": "Nephrolithiasis (NL)", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "No significant difference in urinary excretion between groups; not a useful biomarker in this context.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "N-glycosylation influences serum and urinary levels.", "mechanism": "AAT is a known marker for chronic kidney disease and inflammatory renal conditions.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Vasculitis", "glycan_involvement": "N-glycosylation modulates anti-inflammatory activity.", "mechanism": "AAT is elevated in inflammatory kidney diseases including vasculitis.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "N-glycosylation affects serum half-life and function.", "mechanism": "Serum fetuin-A is associated with insulin resistance and diabetes.", "protein": "Alpha-2-HS-glycoprotein (Fetuin-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Kidney tubular injury", "glycan_involvement": "N-glycosylation impacts renal excretion.", "mechanism": "Urinary fetuin-A is increased in tubular injury, interstitial fibrosis, and atrophy.", "protein": "Alpha-2-HS-glycoprotein (Fetuin-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12649397" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "N-glycosylation required for renal protective functions.", "mechanism": "AMBP attenuates acute kidney injury and inflammation, promotes tissue repair.", "protein": "Alpha-1-microglobulin/bikunin precursor (AMBP)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12649397" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Chondroitin sulfate glycosylation; impacts ECM remodeling and immune cell recruitment.", "mechanism": "Upregulated VCAN correlates with renal function decline, proteinuria, and immune cell infiltration (regulatory T cells, NK cells, dendritic cells); promotes fibrosis and inflammation.", "protein": "VCAN", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12649795" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "O-glycan biosynthesis; modulates ECM and immune microenvironment.", "mechanism": "Upregulated GCNT3 is associated with decreased GFR and increased fibrosis; linked to ECM proteoglycans and NK cell-mediated inflammation.", "protein": "GCNT3", "protein_enriched": { "function": "Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regul", "gene_name": "NCKAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2A7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12649795" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Initiates O-glycosylation; affects cell proliferation, immune surveillance, and fibrosis.", "mechanism": "Upregulated GALNT7 correlates with renal function decline and increased serum creatinine; involved in immune cell infiltration and O-glycosylation-dependent signaling.", "protein": "GALNT7", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor", "gene_name": "GALNT16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8N428" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Lysosomal glycan hydrolysis; impacts immune cell function.", "mechanism": "Upregulated HEXB in DN; correlates with immune cell infiltration (gamma delta T cells, Th1, activated CD8 T cells); negatively correlated with albumin/creatinine ratio in mouse model.", "protein": "HEXB", "protein_enriched": { "function": "Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from cert", "gene_name": "HEXB", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02402FF", "G22768VO", "G25386IJ", "G51623PN", "G02815KT", "G05724UK", "G10486CT", "G10601XM", "G23719VF", "G28681TP", "G31852PQ", "G39446WN", "G40926MX", "G41247ZX", "G43734MM", "G43947VZ", "G49906RN", "G92050GC", "G00912UN", "G01650EU", "G06110VR", "G25079LO", "G28541PG", "G34989PA", "G37412TK", "G39188ZX", "G43223CG", "G47644PP", "G50282JC", "G55132BD", "G62765YT", "G64409MC", "G80920RR", "G82348BZ", "G82443XX", "G84349RE", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G92275SC", "G95865ZB", "G08011QI", "G74724QE", "G84155GY", "G88989HA", "G49108TO" ], "uniprot_id": "P07686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Beta-1,4-galactosylation; impacts lactosylceramide synthesis and immune signaling.", "mechanism": "Upregulated B4GALT5 in DN; associated with T helper cell and activated CD4 T cell infiltration; may regulate inflammatory and immunomodulatory responses.", "protein": "B4GALT5", "protein_enriched": { "function": "Catalyzes the transfer of Gal to GlcNAc-based acceptors with a preference for the core3 O-linked glycan GlcNAc(beta1,3)GalNAc structure. Can use glycolipid LC3Cer as an efficient acceptor", "gene_name": "B3GALT5", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G82348BZ" ], "uniprot_id": "Q9Y2C3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Glycoprotein hormone alpha subunit; glycosylation affects hormone stability and immune modulation.", "mechanism": "Downregulated CGA in DN; high diagnostic value; positively correlated with neutrophil infiltration, negatively with activated CD8 T cell and NK cell.", "protein": "CGA", "protein_enriched": { "function": "Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH, follitropin/follicle stimulating hormone/FSH and chor", "gene_name": "CGA", "glycan_count": 114, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04077XA", "G06209KS", "G06356OH", "G08185DV", "G10258MC", "G14047PA", "G14358WN", "G14996IQ", "G14998UC", "G16828VN", "G22310AV", "G24413UY", "G24835MQ", "G24954RW", "G25835MT", "G26403SG", "G29857RC", "G36191CD", "G38217AM", "G39540XG", "G40671AG", "G41708PN", "G43346PX", "G43664YB", "G46422KL", "G48414YA", "G49743VF", "G51367TM", "G53933HU", "G53962WT", "G53985AY", "G54612UD", "G56271TF", "G56345UO", "G57196QI", "G62765YT", "G65890UA", "G69411IG", "G72291OX", "G77198CF", "G77252PU", "G78059CC", "G78890OB", "G81198YO", "G83951ZY", "G84467IZ", "G86357DX", "G91365ZQ", "G93284HQ", "G96921ZU", "G99897FQ", "G06110VR", "G11870QZ", "G16758MX", "G23294PN", "G24131KD", "G31372JR", "G39188ZX", "G39917RN", "G42358LZ", "G42826YI", "G44659VQ", "G55504WE", "G80678MA", "G82463GQ", "G97028UT", "G99679NM", "G57321FI", "G49108TO", "G00031MO", "G01614ZM", "G11457RF", "G12398HZ", "G15169WU", "G16155TD", "G17689DH", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G29880MM", "G29931IJ", "G33609NS", "G45209NR", "G45560HM", "G46748BU", "G47518TP", "G50045TK", "G52428MJ", "G52527GH", "G52934AK", "G56318NV", "G56682BC", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G65562ZE", "G66088HZ", "G69834CE", "G70375MX", "G72735IY", "G72797UR", "G74645FT", "G74722FL", "G78030KJ", "G78790NZ", "G79568CQ", "G81006GJ", "G91413ZX", "G91636VS", "G94531EZ", "G95898GD", "G98366ZJ" ], "uniprot_id": "P01215" }, "relationship_type": "biomarker", "source_pmcid": "PMC12649795" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "N-glycosylation; modulates immune response and inflammation.", "mechanism": "Altered IgG N-glycosylation (galactosylation, sialylation) associated with DN prevalence and faster kidney function decline.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Albuminuria in T1D", "glycan_involvement": "N-glycosylation; impacts complement activation and inflammation.", "mechanism": "Enhanced C3 N-glycome in T1D patients with severe albuminuria; correlates with increased HbA1c.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Core fucosylation (N-glycan); modulates TGF-beta signaling and fibrosis.", "mechanism": "Inhibition of FUT8-mediated core fucosylation blocks Smad2/3 and ERK signaling, exerting renoprotective effects.", "protein": "FUT8", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12649795" }, { "confidence": "medium", "disease": "Cancer Immune Escape", "glycan_involvement": "Aberrant glycosylation; alters dendritic cell function and immune surveillance.", "mechanism": "Hyperglycosylation of prosaposin in tumor dendritic cells promotes immune escape.", "protein": "Prosaposin", "relationship_type": "causal", "source_pmcid": "PMC12649795" }, { "confidence": "high", "disease": "Bladder Cancer", "glycan_involvement": "Impaired glycosylation (minimal sialylation) in UT-B1\u039424 isoform in tumors.", "mechanism": "Downregulation and aberrant splicing of UT-B associated with increased risk and progression.", "protein": "UT-B (SLC14A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma", "glycan_involvement": "Glycosylation enhances membrane localization and urea transport activity.", "mechanism": "Phosphorylation and ubiquitination regulate UT-A1 degradation, impacting tumor cell metabolism.", "protein": "UT-A1", "protein_enriched": { "function": "Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism", "gene_name": "SLC14A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q15849" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma", "glycan_involvement": "Sialylation by ST6GalI is crucial for function; loss reduces activity.", "mechanism": "Highly glycosylated UT-A3 stabilizes membrane expression and urea reabsorption.", "protein": "UT-A3", "protein_enriched": { "function": "Exonuclease that has both 3'-5' exoribonuclease and exodeoxyribonuclease activities, depending on the divalent metal cation used as cofactor (PubMed:29335528, PubMed:31127291). In presence of Mg(2+), ", "gene_name": "EXD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NVH0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Not directly specified.", "mechanism": "Low SLC14A1 expression and high promoter methylation correlate with progression and poor prognosis.", "protein": "UT-B (SLC14A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Not directly specified.", "mechanism": "UT-B stabilizes T\u03b2RII, enhancing TGF-\u03b2/Smad signaling and promoting metastasis.", "protein": "UT-B (SLC14A1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Not directly specified.", "mechanism": "Overexpression induces mitochondrial dysfunction and apoptosis, suppressing tumor growth.", "protein": "UT-B (SLC14A1)", "relationship_type": "protective", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Not directly specified.", "mechanism": "SNP rs9952980 reduces SLC14A2 expression, associated with increased risk.", "protein": "SLC14A2 (UT-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia", "glycan_involvement": "Not directly specified.", "mechanism": "SLC14A1 acts as an endocytosis- and m6A-related gene, affecting AML progression.", "protein": "UT-B (SLC14A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "Not directly specified.", "mechanism": "Downregulation promotes proliferation and migration; overexpression suppresses tumor growth.", "protein": "UT-B (SLC14A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "low", "disease": "Esophageal Squamous Cell Carcinoma", "glycan_involvement": "Not directly specified.", "mechanism": "SNPs in SLC14A2 associated with susceptibility.", "protein": "SLC14A2 (UT-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12649947" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Reduced Fc-region sialylation (mainly \u03b12,6-linked).", "mechanism": "Hyposialylated IgG promotes inflammation and insulin resistance via increased Fc\u03b3 receptor binding.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Loss of terminal sialic acids on Fc-region.", "mechanism": "Hyposialylated IgG enhances endothelial inflammation and plaque instability.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12650102" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Sialylation state (number of sialic acids) alters lipid metabolism.", "mechanism": "Higher disialylated apoC-III2 correlates with lower triglycerides and LDL, reducing cardiometabolic risk.", "protein": "Apolipoprotein C-III (apoC-III)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "N-glycan sialic acid removal modulates receptor activation.", "mechanism": "Desialylation by NEU1 enhances IR activation; NEU1 deficiency impairs insulin signaling.", "protein": "Insulin Receptor (IR)", "protein_enriched": { "function": "Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS", "gene_name": "INSR", "glycan_count": 83, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G80920RR", "G11101UV", "G31852PQ", "G56014GC", "G62765YT", "G72951AH", "G81315DD", "G83460ZZ", "G02815KT", "G05049YU", "G10486CT", "G15664MX", "G41247ZX", "G55220VL", "G64527OM", "G72747WU", "G90659AW", "G92406TI", "G00395TQ", "G00912UN", "G07246CJ", "G07483YN", "G08918WF", "G14972EH", "G27058EU", "G41071NU", "G42466VF", "G45395BF", "G47644PP", "G59626AS", "G83646BJ", "G87661QW", "G04657PL", "G05962QB", "G12341GU", "G20312EM", "G39203UC", "G57776ZS", "G60834IK", "G70232NH", "G77582RK", "G80075MS", "G10819WX", "G13131HA", "G16125XL", "G20706XG", "G27947YN", "G29545VG", "G35541EV", "G37818NZ", "G39471UU", "G40926MX", "G43223CG", "G49755GI", "G49906RN", "G55132BD", "G58087IP", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G81263BG", "G85282JO", "G86880BF", "G87123QX", "G93718GY", "G96577RX", "G05724UK", "G20528HD", "G07755XJ", "G54010QB", "G50303LH", "G29068FM", "G43417UB", "G58001LT", "G01650EU", "G23294PN", "G23984SE", "G28541PG", "G37399XV", "G70223PD", "G95865ZB" ], "uniprot_id": "P06213" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Sialylated glycosphingolipid accumulation in adipose tissue.", "mechanism": "Increased GM3 impairs IR localization and signaling, promoting insulin resistance.", "protein": "GM3 Ganglioside", "relationship_type": "causal", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "\u03b12,6-sialylation of glycoproteins (N-glycans).", "mechanism": "Downregulation promotes adipogenesis and weight gain; overexpression inhibits adipocyte differentiation.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "\u03b12,3-sialylation of gangliosides (GM3 biosynthesis).", "mechanism": "Increased ST3GAL5/GM3 impairs insulin signaling and promotes inflammation; knockout improves insulin sensitivity.", "protein": "ST3GAL5 (GM3 synthase)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12650102" }, { "confidence": "medium", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Desialylation of glycolipids/glycoproteins.", "mechanism": "NEU3 upregulation increases ceramide and hepatic lipid accumulation; inhibition reduces steatosis and inflammation.", "protein": "NEU3", "protein_enriched": { "function": "Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes th", "gene_name": "NANS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NR45" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12650102" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Sialic acid-dependent recognition on \u03b2-cells.", "mechanism": "Downregulated in \u03b2-cells in diabetes; restoration reduces cytokine production and preserves \u03b2-cell function.", "protein": "Siglec-7", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl ", "gene_name": "SIGLEC7", "glycan_count": 33, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G55220VL", "G05724UK", "G06110VR", "G06356OH", "G06656BE", "G08606CV", "G21196UL", "G22140GZ", "G22310AV", "G23863VK", "G27102CT", "G29880MM", "G39188ZX", "G39943KJ", "G46687AB", "G48414YA", "G49108TO", "G49874UX", "G50045TK", "G57141NR", "G57818FI", "G67030CA", "G72797UR", "G73455AR", "G75727PF", "G80155BS", "G80858MF", "G81295CK", "G84452RH", "G90093AU", "G90206GU", "G98068RN", "G98205FV" ], "uniprot_id": "Q9Y286" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12650102" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Sialic acid-binding on immune cells.", "mechanism": "Siglec-1+ monocytes infiltrate islets, accelerate disease onset, and correlate with disease activity.", "protein": "Siglec-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12650102" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Defective O-glycosylation (core-1/core-3, Tn/sTn antigens)", "mechanism": "Loss or truncation of O-glycans on MUC2 impairs mucus barrier, increases bacterial penetration, and triggers inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Accumulation of Tn/sTn antigens due to impaired glycan extension", "mechanism": "Truncated O-glycans (Tn/sTn) on MUC2 associate with neoplastic progression and increased tumorigenesis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Chronic Colitis", "glycan_involvement": "Loss of core-1/core-3 O-glycans and sulfation", "mechanism": "Reduced O-glycosylation and sulfation weaken mucus barrier, increasing susceptibility to chronic inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Intestinal Infection", "glycan_involvement": "Dense O-glycans, sialylation, and sulfation", "mechanism": "Intact O-glycosylation and terminal modifications protect against pathogen invasion.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12650285" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Sialyl-Tn antigen formation via ST6GALNAC1", "mechanism": "Inflammation-induced sialyl-Tn formation on MUC1 is linked to cancer-associated glycan termini.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Loss of core-3 O-glycans", "mechanism": "Knockout of B3GNT6 reduces core-3 O-glycans, leading to mucus thinning and increased tumorigenesis.", "protein": "B3GNT6", "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Loss of \u03b11,2-fucosylation", "mechanism": "Non-secretor genotype (FUT2 deficiency) leads to absence of \u03b11,2-fucosylated mucins, altered microbiota, and increased disease risk.", "protein": "FUT2", "protein_enriched": { "function": "Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose on both O- and N-linked glycans chains of cell surface glycoproteins and glycolipids and the r", "gene_name": "FUT2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q10981" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Reduced \u03b12,6-sialylation of O-glycans", "mechanism": "Deficiency in ST6GALNAC1 reduces mucin sialylation, increasing susceptibility to inflammation.", "protein": "ST6GALNAC1", "protein_enriched": { "function": "The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable ", "gene_name": "BBS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3SYG4" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Loss of GlcNAc-6-O-sulfation", "mechanism": "Reduced sulfation of mucin O-glycans compromises mucus barrier and exacerbates colitis.", "protein": "GlcNAc6ST-2/CHST4", "protein_enriched": { "function": "Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of internal galactose (Gal) residues of keratan. Cooperates wi", "gene_name": "CHST1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G90734RJ" ], "uniprot_id": "O43916" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Chronic Colitis", "glycan_involvement": "Defective core-1 O-glycosylation", "mechanism": "Loss of core-1 O-glycan synthesis breaches mucus barrier and elicits spontaneous colitis.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC12650285" }, { "confidence": "high", "disease": "Dystroglycanopathies (DGPs)", "glycan_involvement": "Defective O-mannosylation on \u03b1-DG mucin-like domain", "mechanism": "Impaired O-mannosyl glycosylation of \u03b1-DG reduces its binding to ECM proteins, disrupting tissue integrity.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Dystroglycanopathies (DGPs)", "glycan_involvement": "O-mannosylation (core M3) of \u03b1-DG", "mechanism": "Loss-of-function mutations in POMGNT2 impair core M3 O-mannosyl glycan synthesis on \u03b1-DG, causing DGPs.", "protein": "POMGNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:10464263, ", "gene_name": "GALNT6", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8NCL4" }, "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Dystroglycanopathies (DGPs)", "glycan_involvement": "O-mannosylation (core M1/M2) of \u03b1-DG", "mechanism": "POMGNT1 deficiency disrupts core M1/M2 O-mannosyl glycan synthesis on \u03b1-DG, leading to DGPs.", "protein": "POMGNT1", "protein_enriched": { "function": "Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synth", "gene_name": "POMGNT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WZA1" }, "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Ocular defects (retinal malformations, cataracts, myopia, glaucoma)", "glycan_involvement": "O-mannosylation of \u03b1-DG required for ECM binding", "mechanism": "Hypoglycosylated \u03b1-DG impairs interaction with retinal ECM proteins (e.g., pikachurin), disrupting synapse formation and retinal structure.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Aberrant neuronal migration/axon guidance defects", "glycan_involvement": "O-mannosylation (core M3) of \u03b1-DG", "mechanism": "POMGNT2 knockout leads to defective \u03b1-DG glycosylation, resulting in abnormal neuronal migration in brain development.", "protein": "POMGNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:10464263, ", "gene_name": "GALNT6", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8NCL4" }, "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "medium", "disease": "Carcinomas (increased metastasis)", "glycan_involvement": "O-mannosylation (core M3) of \u03b1-DG", "mechanism": "Defective core M3 glycosylation by POMGNT2 is associated with increased metastasis in some carcinomas.", "protein": "POMGNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:10464263, ", "gene_name": "GALNT6", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q8NCL4" }, "relationship_type": "causal/association", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Dystroglycanopathies (DGPs)", "glycan_involvement": "O-mannosylation initiation on \u03b1-DG", "mechanism": "POMT1 initiates O-mannosylation of \u03b1-DG; mutations cause DGPs.", "protein": "POMT1", "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Fukuyama congenital muscular dystrophy", "glycan_involvement": "O-mannosylation pathway of \u03b1-DG", "mechanism": "FKTN mutations impair \u03b1-DG glycosylation, causing Fukuyama CMD.", "protein": "FKTN (Fukutin)", "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Limb-girdle muscular dystrophies", "glycan_involvement": "O-mannosylation pathway of \u03b1-DG", "mechanism": "FKRP mutations disrupt \u03b1-DG glycosylation, leading to limb-girdle muscular dystrophy.", "protein": "FKRP", "protein_enriched": { "function": "Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-", "gene_name": "FKRP", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G79666IR", "G02815KT", "G49108TO" ], "uniprot_id": "Q9H9S5" }, "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Dystroglycanopathies (DGPs)", "glycan_involvement": "O-mannosylation extension on \u03b1-DG", "mechanism": "LARGE1 is required for final steps of \u03b1-DG glycosylation; mutations cause DGPs.", "protein": "LARGE1", "protein_enriched": { "function": "Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking", "gene_name": "HEATR5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2D3" }, "relationship_type": "causal", "source_pmcid": "PMC12650532" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Fab N-glycans introduced by somatic hypermutation; highly sialylated.", "mechanism": "High Fab N-glycosylation (especially sialylation) in ACPA-IgG predicts RA onset and may facilitate autoreactive B cell survival.", "protein": "ACPA-IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12650748" }, { "confidence": "high", "disease": "Pregnancy (immune tolerance)", "glycan_involvement": "Asymmetric Fab N-glycans (often oligomannose) block antigen binding.", "mechanism": "Increased Fab-glycosylated IgG promotes maternal-fetal immune tolerance by blocking antigen recognition.", "protein": "IgG Fab-glycosylated", "relationship_type": "protective", "source_pmcid": "PMC12650748" }, { "confidence": "high", "disease": "Follicular lymphoma", "glycan_involvement": "Somatic mutation introduces Fab N-glycosylation motifs; oligomannose structures.", "mechanism": "Fab N-glycans (oligomannose) in BCRs interact with lectins, providing survival signals to malignant B cells.", "protein": "IgG Fab-glycosylated", "relationship_type": "causal", "source_pmcid": "PMC12650748" }, { "confidence": "medium", "disease": "Solid tumors (e.g., gastric cancer)", "glycan_involvement": "Fab N-glycans (mannose-rich) detected by ConA binding.", "mechanism": "High serum ConA-enriched IgG (Fab-glycosylated) correlates with poor prognosis; promotes tumor growth and immune escape.", "protein": "ConA-enriched IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12650748" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Sialylated N-glycans in Fab region.", "mechanism": "Fab sialylation activates c-Met/Akt/Erk signaling, promoting cancer cell stemness and tumor progression.", "protein": "Cancer-derived IgG", "relationship_type": "causal", "source_pmcid": "PMC12650748" }, { "confidence": "high", "disease": "Tumor immune escape", "glycan_involvement": "High Fab N-glycosylation (especially sialylation); increased in tumors.", "mechanism": "IgG4 acts as a blocking antibody, inhibits IgG1-mediated immune clearance, and promotes immune tolerance.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal", "source_pmcid": "PMC12650748" }, { "confidence": "high", "disease": "IgG4-related disease", "glycan_involvement": "Fab N-glycans, mainly sialylated.", "mechanism": "Elevated serum IgG4 with increased Fab N-glycosylation (sialylation) is characteristic of disease.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12650748" }, { "confidence": "medium", "disease": "Pemphigus vulgaris", "glycan_involvement": "Fab N-glycans increased.", "mechanism": "Elevated Fab glycosylation in anti-Dsg3 IgG correlates with disease.", "protein": "Anti-Dsg3 IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12650748" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis", "glycan_involvement": "Fab N-glycans increased.", "mechanism": "Increased Fab glycosylation in anti-PR3/MPO IgG observed in AAV.", "protein": "Anti-PR3/MPO IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12650748" }, { "confidence": "medium", "disease": "Tumor immune escape", "glycan_involvement": "Fab N-glycosylation at N88; sialylation increases Fc\u03b3RIIIa affinity.", "mechanism": "Engineering Fab N-glycans (e.g., sialylation) enhances ADCC and alters antigen recognition, improving therapeutic efficacy.", "protein": "Cetuximab", "protein_enriched": { "function": "Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and break", "gene_name": "C1R", "glycan_count": 60, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G02030ZB", "G08918WF", "G11629QQ", "G15169WU", "G22310AV", "G39595FH", "G48414YA", "G59536GA", "G64394MX", "G81263BG", "G84452RH", "G92050GC", "G92275SC", "G04562GJ", "G10486CT", "G22768VO", "G27058EU", "G27947YN", "G31852PQ", "G34617SM", "G37399XV", "G41247ZX", "G41882MT", "G45504EY", "G47748JZ", "G54963QY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G72787SB", "G78790NZ", "G80920RR", "G93656SY", "G95865ZB", "G98611JV", "G04657PL", "G04854VP", "G06247RL", "G10488MI", "G20706XG", "G27126ED", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G60033FS", "G61256FT", "G63980BQ", "G70232NH", "G77669RF", "G90382BL", "G94470IW", "G49108TO" ], "uniprot_id": "P00736" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12650748" }, { "confidence": "high", "disease": "Diabetic complications", "glycan_involvement": "Binds advanced glycation end-products (AGEs); glycosylation affects ligand binding.", "mechanism": "RAGE activation by AGEs leads to chronic inflammation and tissue damage.", "protein": "RAGE (Receptor for Advanced Glycation End-Products)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "high", "disease": "Vascular disease", "glycan_involvement": "Binds glycated proteins; glycosylation modulates receptor function.", "mechanism": "RAGE-mediated signaling promotes vascular inflammation and dysfunction.", "protein": "RAGE (Receptor for Advanced Glycation End-Products)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation influences \u03b2-amyloid binding.", "mechanism": "RAGE binds \u03b2-amyloid, promoting neuroinflammation and amyloid pathology.", "protein": "RAGE (Receptor for Advanced Glycation End-Products)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Binds S100 proteins and other glycoproteins; glycosylation modulates ligand interactions.", "mechanism": "RAGE activation drives pro-inflammatory and pro-migratory signaling, supporting tumor progression.", "protein": "RAGE (Receptor for Advanced Glycation End-Products)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Integrin glycosylation required for surface expression and function.", "mechanism": "Upregulated by RAGE; promotes cell adhesion and spreading, facilitating tumor cell migration.", "protein": "ITGA8 (Integrin alpha 8)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "N-glycosylation critical for integrin function.", "mechanism": "RAGE-dependent upregulation of ITGA8 enhances adhesion and spreading in pancreatic cancer cells.", "protein": "ITGA8 (Integrin alpha 8)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "EMT (Epithelial-Mesenchymal Transition)", "glycan_involvement": "GPI-anchored glycoprotein; glycosylation affects cell-cell interactions.", "mechanism": "RAGE upregulates CNTN1, which is implicated in EMT and metastasis.", "protein": "CNTN1 (Contactin-1)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "Malignant melanoma", "glycan_involvement": "Glycosylation modulates ligand binding.", "mechanism": "MCAM and RAGE both bind S100A8/A9, mediating melanoma cell signaling.", "protein": "MCAM (Melanoma Cell Adhesion Molecule)", "protein_enriched": { "function": "Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)", "gene_name": "GLG1", "glycan_count": 105, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00273SJ", "G00912UN", "G01650EU", "G08918WF", "G10773YW", "G10819WX", "G10846ZT", "G11314AS", "G12313PD", "G14972EH", "G15664MX", "G20210JR", "G20706XG", "G23294PN", "G23984SE", "G24084IV", "G25418HZ", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G31852PQ", "G31986NC", "G37412TK", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G44215PV", "G45395BF", "G45504EY", "G47012YE", "G47644PP", "G48414YA", "G48584BU", "G54612UD", "G57776ZS", "G59626AS", "G60834IK", "G62765YT", "G63041LO", "G63980BQ", "G70441OD", "G70619PT", "G75983OB", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83646BJ", "G84452RH", "G84820NF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G90734RJ", "G91636VS", "G92062TF", "G92135MA", "G95865ZB", "G96091TT", "G98611JV", "G02628JF", "G02815KT", "G04657PL", "G08290VR", "G17208MA", "G25451PN", "G26915XM", "G34989PA", "G41882MT", "G43669FQ", "G47448YK", "G56284ZY", "G58954YZ", "G61256FT", "G63381RX", "G64409MC", "G65019XG", "G70101JE", "G75607BQ", "G76295SF", "G77547TA", "G81198YO", "G90093AU", "G91255CS", "G92551JA", "G94470IW", "G95977AE", "G49108TO", "G37399XV", "G43417UB", "G06356OH", "G60177UT", "G64527OM", "G74430RZ" ], "uniprot_id": "Q92896" }, "relationship_type": "biomarker", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "Tissue repair/wound healing", "glycan_involvement": "Glycosylation required for ECM assembly.", "mechanism": "Downregulated by RAGE; FN1 is essential for tissue repair and wound healing.", "protein": "FN1 (Fibronectin 1)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "medium", "disease": "Tissue repair/wound healing", "glycan_involvement": "Glycosylation modulates ECM interactions.", "mechanism": "Downregulated by RAGE; THBS1 is involved in tissue repair.", "protein": "THBS1 (Thrombospondin-1)", "relationship_type": "causal", "source_pmcid": "PMC12650875" }, { "confidence": "high", "disease": "Pediatric heart failure", "glycan_involvement": "Glycosylation affects BNP stability and clearance.", "mechanism": "Elevated BNP reflects ventricular strain and severity of heart failure.", "protein": "B-type natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "high", "disease": "Fulminant myocarditis", "glycan_involvement": "O-glycosylation modulates NT-proBNP immunoreactivity and half-life.", "mechanism": "Markedly elevated NT-proBNP indicates severe myocardial injury and acute decompensation.", "protein": "N-terminal pro-BNP (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "high", "disease": "Fulminant myocarditis", "glycan_involvement": "Fc N-glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG used for immunomodulation in inflammatory myocarditis phenotype.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12650898" }, { "confidence": "medium", "disease": "Fulminant myocarditis", "glycan_involvement": "Glycosylation may affect cTnI stability and detection.", "mechanism": "Elevated cTnI indicates acute myocardial injury.", "protein": "Cardiac troponin I (cTnI)", "protein_enriched": { "function": "With S4 and S5 plays an important role in translational accuracy. Located at the interface of the 30S and 50S subunits (By similarity)", "gene_name": "rps12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19461" }, "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "medium", "disease": "Fulminant myocarditis", "glycan_involvement": "Glycosylation influences CK-MB serum half-life.", "mechanism": "Elevated CK-MB reflects myocardial cell damage.", "protein": "Creatine kinase-MB (CK-MB)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with larg", "gene_name": "CKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "medium", "disease": "Hypertensive heart failure", "glycan_involvement": "N-glycosylation regulates ACE activity and cell surface expression.", "mechanism": "ACE inhibitors used to manage hypertension and cardiorenal syndrome.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12650898" }, { "confidence": "medium", "disease": "Hypertensive heart failure", "glycan_involvement": "N-glycosylation affects receptor trafficking and ligand binding.", "mechanism": "Beta-blockers modulate adrenergic signaling in chronic heart failure.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12650898" }, { "confidence": "low", "disease": "Preterm birth complications", "glycan_involvement": "Glycosylation may modulate titin elasticity and function.", "mechanism": "Abnormal titin isoform ratios contribute to myocardial stiffness in preterm infants.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "causal", "source_pmcid": "PMC12650898" }, { "confidence": "low", "disease": "Congenital heart disease (CHD)", "glycan_involvement": "Glycosylation regulates platelet glycoprotein function.", "mechanism": "Elevated platelet counts in CHD-associated heart failure may reflect altered platelet activation.", "protein": "Platelet glycoprotein IIb/IIIa", "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "low", "disease": "Multi-organ dysfunction", "glycan_involvement": "N-glycosylation status affects transferrin function and diagnostic use.", "mechanism": "Altered transferrin levels may indicate hepatic dysfunction in severe heart failure.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12650898" }, { "confidence": "high", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Glycosylation affects plasma stability and function.", "mechanism": "Involved in amyloid-\u03b2 sequestration; lower levels associated with higher MCI risk.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "high", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Glycosylation modulates stability and amyloid binding.", "mechanism": "Involved in amyloid-\u03b2 clearance; lower TTR correlates with higher MCI risk.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "N-glycosylation critical for complement activation.", "mechanism": "Elevated C3 correlates with inflammation and MCI risk.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Glycosylation influences lipid metabolism and immune function.", "mechanism": "Lower ApoC1 associated with higher periodontal inflammation and MCI risk.", "protein": "Apolipoprotein C1 (ApoC1)", "protein_enriched": { "function": "Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoprotein", "gene_name": "APOC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02654" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "N-glycosylation affects plasma half-life.", "mechanism": "Elevated HPX correlates with inflammation and MCI risk.", "protein": "Hemopexin (HPX)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "N-glycosylation essential for function.", "mechanism": "Higher A2M in high periodontal inflammation group; involved in protease inhibition and amyloid clearance.", "protein": "Alpha-2-Macroglobulin (A2M)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "medium", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "CRP correlates with ApoA1, C3, and HPX; reflects systemic inflammation linked to MCI risk.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "low", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Highly glycosylated; glycan structure affects function.", "mechanism": "Lower A1BG in high inflammation group; involved in innate immunity.", "protein": "Alpha-1-B-Glycoprotein (A1BG)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "low", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "N-glycosylation affects inhibitory activity.", "mechanism": "Lower A2AP in high inflammation group; involved in coagulation/fibrinolysis.", "protein": "Alpha-2-Anti Plasmin (A2AP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "low", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "Minor glycosylation; may affect half-life.", "mechanism": "Lower albumin in high inflammation group; reflects nutritional status and amyloid binding.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651057" }, { "confidence": "high", "disease": "General Tumors (solid and hematologic)", "glycan_involvement": "Glycosylation of VSV-G affects receptor binding and immune evasion.", "mechanism": "Mediates VSV entry into tumor cells via LDL-R; broad tropism enables oncolytic virotherapy.", "protein": "VSV-G", "protein_enriched": { "function": "Attaches the virus to host LDL receptors, inducing clathrin-dependent endocytosis of the virion (PubMed:20941355, PubMed:23589850). In the endosome, the acidic pH induces conformational changes in the", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03522" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "\u03b1-dystroglycan is highly glycosylated; LCMV-GP binding depends on glycan structures.", "mechanism": "Chimeric VSV-GP redirects viral entry to \u03b1-dystroglycan, sparing neurons and targeting glioma cells.", "protein": "LCMV-GP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "NDV-HN/F glycosylation modulates fusogenicity and immune recognition.", "mechanism": "Chimeric VSV-NDV uses NDV glycoproteins for tumor entry and immunogenic cell death.", "protein": "NDV-HN/F", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "Ewing Sarcoma", "glycan_involvement": "Glycosylation may affect tropism and immune response.", "mechanism": "VMG (VSV with Morreton glycoprotein) enables broad oncolytic activity and immune engagement.", "protein": "Morreton Virus Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "LASV-GP glycosylation critical for receptor binding and immune evasion.", "mechanism": "LASV-VSV targets ovarian cancer, showing oncolysis and systemic immunity.", "protein": "LASV-GP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Mucin-like domain is heavily O-glycosylated, mediating selectivity and immune evasion.", "mechanism": "Chimeric VSV-EBOV-GP selectively kills GBM cells, sparing normal brain tissue.", "protein": "EBOV-GP (mucin-like domain)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Specific O-mannosyl glycosylation required for LCMV-GP binding.", "mechanism": "Acts as entry receptor for LCMV-GP; glycosylation status determines susceptibility.", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "General Tumors (solid and hematologic)", "glycan_involvement": "LDL-R is N-glycosylated, affecting receptor function.", "mechanism": "Ubiquitous expression enables VSV-G mediated infection of tumor cells.", "protein": "LDL-R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "Breast Cancer (implied in HER2-targeting)", "glycan_involvement": "HER2 is N-glycosylated; glycosylation affects receptor conformation and targeting.", "mechanism": "Chimeric VSVs engineered to target HER2 enhance tumor selectivity.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "medium", "disease": "Pancreatic Ductal Adenocarcinoma (PDAC)", "glycan_involvement": "Mutations may alter glycosylation patterns, affecting tropism.", "mechanism": "Mutations in VSV-G (K174E, E238K) improve attachment and replication in resistant PDAC cells.", "protein": "VSV-G (mutant forms)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12651548" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin interacts with glycosylated dystroglycan complex; glycosylation is essential for complex stability.", "mechanism": "Loss or deficiency of dystrophin destabilizes sarcolemma, leading to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12651955" }, { "confidence": "high", "disease": "Canine X-linked muscular dystrophy", "glycan_involvement": "Dystrophin\u2013glycoprotein complex requires glycosylation for membrane linkage.", "mechanism": "Deletion of DMD exon 5 causes absence of dystrophin, resulting in muscular dystrophy in Shiba Inu dogs.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12651955" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylated dystroglycan complex mediates cardiac muscle stability.", "mechanism": "Dystrophin deficiency leads to myocardial degeneration and fibrosis, causing dilated cardiomyopathy.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12651955" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin is glycosylated and interacts with glycoprotein complexes.", "mechanism": "Upregulation of utrophin in dystrophin-deficient muscle acts as a compensatory response.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651955" }, { "confidence": "medium", "disease": "Canine X-linked muscular dystrophy", "glycan_involvement": "Alpha-sarcoglycan is glycosylated, affecting membrane stability.", "mechanism": "Altered expression in dystrophic muscle; part of sarcoglycan complex affected by dystrophin loss.", "protein": "Alpha-sarcoglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12651955" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Heavily glycosylated; glycosylation required for dystrophin binding.", "mechanism": "Beta-dystroglycan is part of the dystrophin\u2013glycoprotein complex; altered in dystrophin-deficient muscle.", "protein": "Beta-dystroglycan", "relationship_type": "biomarker", "source_pmcid": "PMC12651955" }, { "confidence": "medium", "disease": "Canine X-linked muscular dystrophy", "glycan_involvement": "Glycosylation required for extracellular matrix interactions.", "mechanism": "Laminin alpha2 expression is unchanged in dystrophic muscle, used to distinguish dystrophinopathy.", "protein": "Laminin alpha2", "relationship_type": "biomarker", "source_pmcid": "PMC12651955" }, { "confidence": "medium", "disease": "Canine X-linked muscular dystrophy", "glycan_involvement": "Glycosylation important for matrix assembly.", "mechanism": "Collagen VI expression is unchanged in dystrophic muscle, used as a control marker.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "biomarker", "source_pmcid": "PMC12651955" }, { "confidence": "high", "disease": "Becker muscular dystrophy (BMD)", "glycan_involvement": "Glycosylation of associated complex is required for residual function.", "mechanism": "Partial deficiency or altered dystrophin leads to milder muscular dystrophy phenotype.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12651955" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation is essential for dystroglycan function in heart muscle.", "mechanism": "Disruption of glycosylated dystroglycan complex impairs cardiac muscle stability.", "protein": "Beta-dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC12651955" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Overall N-glycosylation profile changes; increased AGP levels with altered glycosylation.", "mechanism": "AGP concentration is significantly increased in severe COVID-19, reflecting acute-phase response.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Reduced terminal \u03b12,6-linked sialic acid on AGP N-glycans.", "mechanism": "Decreased \u03b12,6-sialylation (SNA-reactive) on AGP is characteristic of severe COVID-19.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Reduced \u03b11,3-fucosylation (Le x) on AGP N-glycans.", "mechanism": "Decreased Lewis x (Le x) fucosylation (LTA-reactive) on AGP is observed in severe COVID-19.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Not fully elucidated; altered glycosylation may modulate antioxidant function.", "mechanism": "AGP may exert antioxidant effects, as higher AGP correlates with lower serum oxidation-reduction potential (sORP).", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "protective", "source_pmcid": "PMC12651980" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "N-glycosylation pattern changes with inflammation severity.", "mechanism": "AGP is a positive acute-phase protein; its concentration increases in inflammation.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "high", "disease": "Severe COVID-19 recovery", "glycan_involvement": "Restoration of SNA-reactive sialic acid and Le x structures on AGP.", "mechanism": "In convalescents, increased \u03b12,6-sialylation and Le x fucosylation on AGP reflect recovery.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Altered glycosylation may influence antioxidant properties.", "mechanism": "AGP levels negatively correlate with sORP, suggesting a role in antioxidant defense during severe COVID-19.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "protective", "source_pmcid": "PMC12651980" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Increased Le x fucosylation on IgG N-glycans.", "mechanism": "IgG glycosylation (Le x fucosylation) increases in severe COVID-19, but \u03b12,6-sialylation and concentration do not change.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Increased \u03b12,6-sialylation and Le x fucosylation on CLU N-glycans.", "mechanism": "CLU concentration decreases in severe COVID-19, with increased SNA-reactive sialic acid and LTA-reactive fucose.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Core fucosylation (\u03b11,6) on AGP N-glycans remains unchanged.", "mechanism": "No significant change in AGP core fucosylation (AAL-reactive) between groups.", "protein": "\u03b11-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12651980" }, { "confidence": "high", "disease": "Ehlers-Danlos syndrome", "glycan_involvement": "Altered glycosylation may affect collagen stability and assembly.", "mechanism": "Mutations in collagen I genes disrupt fibril formation, leading to connective tissue fragility.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "high", "disease": "Ehlers-Danlos syndrome", "glycan_involvement": "Glycosylation influences collagen fibril assembly.", "mechanism": "Mutations in collagen III genes cause vascular and tissue fragility.", "protein": "Collagen III", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A2", "glycan_count": 18, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G25637MV", "G27915IV", "G31852PQ", "G39188ZX", "G40574BA", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G43417UB", "G49108TO" ], "uniprot_id": "P08123" }, "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "high", "disease": "Alport syndrome", "glycan_involvement": "Collagen IV is highly glycosylated, affecting network formation.", "mechanism": "Mutations in COL4A3, COL4A4, COL4A5 disrupt basement membrane integrity in kidneys.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "high", "disease": "Epidermolysis bullosa", "glycan_involvement": "Glycosylation may affect collagen VII stability and immune recognition.", "mechanism": "COL7A1 mutations or autoantibodies impair anchoring fibrils, causing skin blistering.", "protein": "Collagen VII", "protein_enriched": { "function": "Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular ", "gene_name": "COL7A1", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q02388" }, "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "medium", "disease": "Steel syndrome", "glycan_involvement": "Glycosylation may modulate collagen XXVII function.", "mechanism": "COL27A1 mutations disrupt pericellular matrix in growth plate, causing skeletal defects.", "protein": "Collagen XXVII", "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "medium", "disease": "Schmid-type metaphyseal chondrodysplasia", "glycan_involvement": "Glycosylation may affect collagen X folding and secretion.", "mechanism": "COL10A1 mutations impair endochondral ossification.", "protein": "Collagen X", "relationship_type": "causal", "source_pmcid": "PMC12652212" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Chondroitin sulfate and keratan sulfate chains mediate ECM interactions.", "mechanism": "Aggrecan accumulation in vascular ECM contributes to plaque formation.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12652212" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Heparan sulfate chains regulate storage and release of proteases and cytokines.", "mechanism": "SRGN promotes tumor growth, inflammation, and immune modulation.", "protein": "Serglycin (SRGN)", "protein_enriched": { "function": "Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal ", "gene_name": "SRGN", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P10124" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12652212" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Heparan sulfate chains modulate growth factor signaling.", "mechanism": "GPC6 regulates Wnt and Hedgehog signaling, affecting tumor growth and survival.", "protein": "Glypican-6 (GPC6)", "protein_enriched": { "function": "Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases (By similarity). Enhances migrati", "gene_name": "GPC6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q9Y625" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12652212" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation may regulate TN-C interactions with integrins and ECM.", "mechanism": "Persistent high TN-C expression promotes inflammation and fibrotic tissue remodeling.", "protein": "Tenascin-C (TN-C)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12652212" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation may affect detection and function.", "mechanism": "PD-L1 expression predicts response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12652641" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "CD38 is a glycoprotein; glycosylation may influence cell-cell interactions.", "mechanism": "High infiltration of CD38+ plasma cells correlates with longer metastasis-free survival.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "protective", "source_pmcid": "PMC12652641" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects stability and immune function.", "mechanism": "Higher Ig\u03baC expression is associated with better prognosis.", "protein": "Ig\u03baC", "relationship_type": "protective", "source_pmcid": "PMC12652641" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "CD301 binds O-glycosylated Tn and STn antigens on tumor cells.", "mechanism": "CD301-CAR NK cells target glycan structures on osteosarcoma cells, leading to tumor cell lysis.", "protein": "CD301 (CLEC10A)", "protein_enriched": { "function": "Early post-infection, the reverse transcriptase converts the viral RNA genome into double-stranded viral DNA. The RNase H domain of the reverse transcriptase performs two functions. It degrades the RN", "gene_name": "ERVK-6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BXR3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12652641" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "O-glycosylation of serine/threonine residues creates Tn antigen.", "mechanism": "Tn antigen serves as a target for CD301-CAR NK cell-mediated killing.", "protein": "Tn antigen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12652641" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Sialylation of Tn antigen (O-glycosylation) enhances immune evasion and is a tumor marker.", "mechanism": "STn antigen is recognized by CD301-CAR NK cells for tumor cell targeting.", "protein": "Sialyl-Tn antigen (STn)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12652641" }, { "confidence": "medium", "disease": "Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC)", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "Anti-PD1 therapy decreases HBsAg, contributing to viral suppression and cancer control.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12652641" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "LAMP1 is heavily glycosylated; glycosylation is essential for lysosomal function.", "mechanism": "CD107a upregulation indicates NK cell degranulation and tumor cell lysis.", "protein": "CD107a (LAMP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12652641" }, { "confidence": "low", "disease": "Osteosarcoma", "glycan_involvement": "TIGIT is a glycoprotein; glycosylation may modulate receptor-ligand interactions.", "mechanism": "Blocking TIGIT slightly increases NK cell-mediated killing of osteosarcoma cells.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12652641" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "CD14 is a glycoprotein; glycosylation affects immune signaling.", "mechanism": "PD-L1+ CD14+ monocytes in PBMCs serve as a biomarker for ICI response.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12652641" }, { "confidence": "high", "disease": "Sport-related muscle injury", "glycan_involvement": "Collagen is N-glycosylated, affecting ECM structure and repair.", "mechanism": "COL5A1 rs12722 TT genotype leads to stiffer, less extensible connective tissue, increasing risk of muscle strains and tears.", "protein": "Collagen alpha-1(V) chain (COL5A1)", "protein_enriched": { "function": "Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate", "gene_name": "COL5A1", "glycan_count": 22, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ", "G02815KT", "G05724UK", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G64527OM", "G80920RR", "G46503DX", "G70101JE", "G00912UN", "G06356OH", "G11911BT", "G48414YA", "G59626AS", "G66621EA", "G53434XO", "G43417UB", "G27391WQ" ], "uniprot_id": "P20908" }, "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "high", "disease": "Sport-related muscle injury", "glycan_involvement": "Sarcomeric glycoprotein; glycosylation may affect stability.", "mechanism": "ACTN3 R577X (XX genotype) causes \u03b1-actinin-3 deficiency, reducing muscle fiber integrity and increasing injury risk.", "protein": "Alpha-actinin-3 (ACTN3)", "protein_enriched": { "function": "F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein", "gene_name": "ACTN3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q08043" }, "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Sport-related muscle injury", "glycan_involvement": "Secreted glycoprotein; N-glycosylation modulates receptor interaction.", "mechanism": "IGF2 GC genotype associated with less severe muscle injuries; promotes muscle regeneration.", "protein": "Insulin-like growth factor 2 (IGF2)", "relationship_type": "protective", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Exercise-induced muscle damage", "glycan_involvement": "Cytokine glycosylation affects secretion and receptor binding.", "mechanism": "IL6 rs1800795 G allele increases IL-6 expression, linked to higher risk of muscle injury and inflammation.", "protein": "Interleukin-6 (IL6)", "relationship_type": "biomarker", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Sport-related muscle injury", "glycan_involvement": "Membrane glycoprotein; glycosylation influences enzyme activity.", "mechanism": "ACE II genotype linked to higher susceptibility to muscle injury; D allele may be protective.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Sport-related muscle injury", "glycan_involvement": "Enzyme glycosylation may affect stability and localization.", "mechanism": "AMPD1 TT genotype impairs ATP regeneration, increasing risk of muscle injury.", "protein": "Adenosine monophosphate deaminase 1 (AMPD1)", "protein_enriched": { "function": "AMP deaminase plays a critical role in energy metabolism", "gene_name": "AMPD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23109" }, "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Muscle strain/tear", "glycan_involvement": "Glycosylation may regulate caspase activation.", "mechanism": "CASP8 rs3834129 II and DD genotypes associated with more severe muscle injuries via altered apoptosis.", "protein": "Caspase-8 (CASP8)", "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "medium", "disease": "Sport-related muscle injury", "glycan_involvement": "Secreted glycoprotein; glycosylation modulates activity.", "mechanism": "MSTN variants alter muscle growth regulation, potentially increasing injury susceptibility.", "protein": "Myostatin (MSTN)", "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "high", "disease": "Exertional rhabdomyolysis", "glycan_involvement": "Membrane glycoprotein; glycosylation affects channel function.", "mechanism": "RYR1 variants disrupt Ca2+ homeostasis, causing muscle breakdown under exercise stress.", "protein": "Ryanodine receptor 1 (RYR1)", "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "high", "disease": "Malignant hyperthermia", "glycan_involvement": "Glycosylation modulates channel gating and stability.", "mechanism": "RYR1 pathogenic variants trigger uncontrolled Ca2+ release, leading to hyperthermia and muscle damage.", "protein": "Ryanodine receptor 1 (RYR1)", "relationship_type": "causal", "source_pmcid": "PMC12652936" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "N-glycosylation increases on PSAP", "mechanism": "TGF-\u03b2-driven hyperglycosylation of PSAP disrupts chaperone binding and lysosomal targeting, contributing to fibrosis.", "protein": "PSAP", "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Fucosylation (O-glycosylation) of L1CAM", "mechanism": "FUT4-mediated fucosylation of L1CAM alters AR-FUT4-L1CAM-AJ signaling, promoting fibrotic changes.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Pulmonary Fibrosis", "glycan_involvement": "N- and O-glycosylation on MUC6", "mechanism": "Proper glycosylation of MUC6 mediates cell-matrix interactions via clusterin binding, maintaining mucosal integrity.", "protein": "MUC6", "relationship_type": "protective", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Pulmonary Fibrosis", "glycan_involvement": "Loss of N-glycosylation on IL-6", "mechanism": "Deglycosylated IL-6 increases metastatic potential and indirectly leads to pulmonary fibrosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Increased N-glycosylation on ITA3", "mechanism": "Mutation A349S increases glycosylation, interfering with ITA3 biosynthesis and promoting EMT and fibrosis.", "protein": "Integrin \u03b13\u03b21 (ITA3)", "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Pulmonary Fibrosis", "glycan_involvement": "Glycan-dependent interaction", "mechanism": "Glycan\u2013clusterin binding maintains epithelial integrity, counteracting fibrotic remodeling.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation-dependent lectin binding", "mechanism": "Galectin-3 binds glycosylated integrins and TGF-\u03b2RII, modulating fibroblast activation and ECM deposition.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12652984" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "N-glycosylation on receptor subunits", "mechanism": "Glycosylation of TGF-\u03b2RII subunits affects TGF-\u03b2 signaling, driving fibroblast activation.", "protein": "TGF-\u03b2RII", "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Non-enzymatic glycation", "mechanism": "AGEs distinguish IPF from CTD-ILD, serving as diagnostic markers.", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "biomarker", "source_pmcid": "PMC12652984" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Fucosylation (O-glycosylation)", "mechanism": "Upregulated FUT4 increases fucosylation of L1CAM, promoting fibrotic signaling.", "protein": "Fucosyltransferase 4 (FUT4)", "relationship_type": "causal", "source_pmcid": "PMC12652984" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "OPG is a glycoprotein; glycosylation is essential for its stability and secretion.", "mechanism": "Elevated OPG reflects vascular inflammation, endothelial dysfunction, and cardiac remodeling; correlates with HF severity and adverse outcomes.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may affect receptor binding and signaling.", "mechanism": "OPG/RANK/RANKL axis activation promotes matrix metalloproteinase activity, contributing to ventricular remodeling and dysfunction.", "protein": "Osteoprotegerin", "relationship_type": "causal", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation status could influence therapeutic efficacy.", "mechanism": "OPG may be a candidate for targeted therapeutic monitoring in HF due to its role in inflammation and remodeling.", "protein": "Osteoprotegerin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for OPG secretion and function.", "mechanism": "Elevated OPG associated with vascular calcification and chronic inflammation in atherosclerosis.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "Glycosylation impacts OPG stability in circulation.", "mechanism": "Higher circulating OPG observed in CAD patients, reflecting endothelial dysfunction.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Left Ventricular Dysfunction", "glycan_involvement": "Glycosylation may modulate OPG's interaction with cardiac cells.", "mechanism": "OPG levels correlate with increased LV mass and reduced ejection fraction.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation necessary for OPG's biomarker function.", "mechanism": "OPG levels are significantly elevated in NYHA Class II HF, indicating early myocardial stress and vascular inflammation.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects OPG's circulating levels and detection.", "mechanism": "OPG predicts mortality and hospitalization in chronic HF (GISSI-HF trial).", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation required for OPG's stability and measurement.", "mechanism": "Serum OPG at discharge predicts risk of death or readmission in acute HF.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may be altered in advanced disease, affecting OPG levels.", "mechanism": "OPG elevation in HF may plateau or decrease in advanced stages due to cellular dysfunction.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12653011" }, { "confidence": "high", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation of GPIIb/IIIa affects antibody binding and immune recognition.", "mechanism": "Autoantibodies against GPIIb/IIIa induced by viral infection mediate platelet destruction.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "high", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Glycan structures modulate immunogenicity of GPIb-IX-V.", "mechanism": "Viral infection triggers autoantibodies targeting GPIb-IX-V, leading to platelet clearance.", "protein": "Glycoprotein Ib-IX-V (GPIb-IX-V)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation mediates virus-glycoprotein interaction.", "mechanism": "Viruses can bind directly to GPIa/IIa, activating platelets and promoting their destruction.", "protein": "Glycoprotein Ia/IIa (GPIa/IIa)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "CR2 glycosylation influences ligand and immune complex binding.", "mechanism": "Viral binding to CR2 on platelets may facilitate immune-mediated clearance.", "protein": "Complement receptor 2 (CR2)", "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "low", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation affects CXCR4 surface expression and function.", "mechanism": "Viral alteration of CXCR4 modulates platelet function and survival.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "TPO is a glycoprotein; glycosylation is essential for secretion and activity.", "mechanism": "Viruses (e.g., HHV-6/7) alter hepatic TPO production, reducing platelet generation.", "protein": "Thrombopoietin (TPO)", "protein_enriched": { "function": "Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major ", "gene_name": "THPO", "glycan_count": 32, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00227RN", "G00800WJ", "G01817YC", "G14389GM", "G16265MV", "G17689DH", "G44444MB", "G47058MH", "G56501FP", "G57789QC", "G90352XZ", "G94531EZ", "G00031MO", "G01614ZM", "G11629QQ", "G15169WU", "G19075PM", "G22310AV", "G29931IJ", "G39595FH", "G57321FI", "G57581QG", "G64394MX", "G65562ZE", "G69834CE", "G72667IM", "G74722FL", "G81006GJ", "G81263BG", "G84452RH", "G87015RU", "G96170OK" ], "uniprot_id": "P40225" }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "IL-6 glycosylation modulates stability and receptor interaction.", "mechanism": "Viral infection induces IL-6, activating platelets and shortening their lifespan.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "high", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Spike glycosylation shields epitopes and modulates immune activation.", "mechanism": "SARS-CoV-2 infection triggers immune response and autoantibodies against platelet glycoproteins.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Viral glycoprotein glycosylation affects immune mimicry.", "mechanism": "EBV infection induces autoantibodies that cross-react with platelet glycoproteins.", "protein": "Epstein\u2013Barr virus gp350/220", "protein_enriched": { "function": "Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transp", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03186" }, "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "medium", "disease": "Chronic ITP", "glycan_involvement": "Altered glycosylation may enhance autoantigenicity.", "mechanism": "Chronic/persistent viral infections promote ongoing autoantibody production against platelet integrins.", "protein": "Platelet surface integrins (general)", "relationship_type": "causal", "source_pmcid": "PMC12653210" }, { "confidence": "high", "disease": "Rice blast", "glycan_involvement": "N-glycosylation assembly; loss leads to defective glycoproteins.", "mechanism": "MoAlg3 deletion impairs hyphal growth, host colonization, and virulence in Magnaporthe oryzae.", "protein": "MoAlg3", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Fusarium wilt", "glycan_involvement": "N-glycosylation assembly; hypo-glycosylation of cell wall proteins.", "mechanism": "FoGnt2 deletion causes abnormal hyphal morphology, reduced cell wall integrity, and increased host immune activation.", "protein": "FoGnt2", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Verticillium wilt", "glycan_involvement": "N-glycosylation transfer to nascent proteins.", "mechanism": "VdSTT3 deletion reduces growth, conidiation, and pathogenicity in Verticillium dahliae.", "protein": "VdSTT3", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Rice blast", "glycan_involvement": "N-glycan processing; improper glycoprotein folding.", "mechanism": "MoGls1 deletion impairs mycelial growth, sporulation, and host colonization.", "protein": "MoGls1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Rice blast", "glycan_involvement": "N-glycan-dependent protein folding chaperone.", "mechanism": "MoCNX1 deletion reduces sporulation and impairs invasive growth in host tissue.", "protein": "MoCNX1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Soybean root rot", "glycan_involvement": "N-glycosylation at Asn174/Asn190 required for effector stability.", "mechanism": "N-glycosylation of PsXEG1 protects it from host protease and inhibitor, enhancing Phytophthora sojae virulence.", "protein": "PsXEG1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Rice blast", "glycan_involvement": "N-glycosylation at Asn48, Asn104, Asn131.", "mechanism": "N-glycosylation at three sites is essential for MoSlp1 secretion and chitin-binding, suppressing host ROS burst.", "protein": "MoSlp1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Anthracnose", "glycan_involvement": "N-glycan-dependent folding of secreted effectors.", "mechanism": "CgCNX1 deletion blocks penetration and colonization, abolishing disease in Colletotrichum graminicola.", "protein": "CgCNX1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Corn smut", "glycan_involvement": "N-glycan processing; loss leads to misfolded effectors.", "mechanism": "UmGas1 deletion impairs pathogenicity and triggers host ROS and defense gene expression.", "protein": "UmGas1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Verticillium wilt", "glycan_involvement": "N-glycan outer chain elongation.", "mechanism": "VdOch1 deletion reduces growth, conidiation, and micronucleus formation, and impairs cell wall integrity.", "protein": "VdOch1", "relationship_type": "causal", "source_pmcid": "PMC12653241" }, { "confidence": "high", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation at Asn114; not essential for transport regulation.", "mechanism": "NbXTH promotes TMV intercellular transport by loosening cell wall, facilitating viral spread.", "protein": "NbXTH", "relationship_type": "causal", "source_pmcid": "PMC12653722" }, { "confidence": "high", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation present but not required for protective effect.", "mechanism": "NbXTH downregulation increases plant tolerance and survival to TMV infection by restricting viral movement.", "protein": "NbXTH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12653722" }, { "confidence": "medium", "disease": "Potato Virus X (PVX) infection", "glycan_involvement": "N-glycosylation present.", "mechanism": "PVX infection induces NbXTH expression.", "protein": "NbXTH", "relationship_type": "biomarker", "source_pmcid": "PMC12653722" }, { "confidence": "medium", "disease": "Potato Virus Y (PVY) infection", "glycan_involvement": "Not specified.", "mechanism": "XTH9 downregulation in resistant potato plants correlates with hypersensitive response and cell wall reinforcement.", "protein": "XTH9", "relationship_type": "protective", "source_pmcid": "PMC12653722" }, { "confidence": "medium", "disease": "Potato Virus Y (PVY) infection", "glycan_involvement": "Not specified.", "mechanism": "Upregulation of XTH-Xet5 strengthens cell wall in infected potato plants.", "protein": "XTH-Xet5", "relationship_type": "protective", "source_pmcid": "PMC12653722" }, { "confidence": "medium", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation predicted.", "mechanism": "Homologous to NbXTH; likely similar role in facilitating TMV spread in N. tabacum.", "protein": "NtXTH18/NtXTH19", "relationship_type": "causal", "source_pmcid": "PMC12653722" }, { "confidence": "medium", "disease": "Abiotic stress (frost, heat, salt, drought, cadmium)", "glycan_involvement": "N-glycosylation present.", "mechanism": "NbXTH homologs mediate enhanced tolerance to abiotic stresses via cell wall remodeling.", "protein": "NbXTH", "relationship_type": "protective", "source_pmcid": "PMC12653722" }, { "confidence": "high", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation present.", "mechanism": "NbXTH expression is upregulated during TMV infection.", "protein": "NbXTH", "relationship_type": "biomarker", "source_pmcid": "PMC12653722" }, { "confidence": "high", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation present but not essential for this function.", "mechanism": "NbXTH upregulation loosens cell wall, increasing plasmodesmata permeability and viral spread.", "protein": "NbXTH", "relationship_type": "causal", "source_pmcid": "PMC12653722" }, { "confidence": "high", "disease": "Tobacco Mosaic Virus (TMV) infection", "glycan_involvement": "N-glycosylation present but not required for protective effect.", "mechanism": "NbXTH silencing strengthens cell wall, restricts TMV movement, and increases plant survival.", "protein": "NbXTH", "relationship_type": "protective", "source_pmcid": "PMC12653722" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation of complex components is critical for membrane stability.", "mechanism": "Loss of dystrophin disrupts the glycoprotein complex at the muscle membrane, impairing linkage between cytoskeleton and extracellular matrix.", "protein": "Dystrophin-associated glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12653760" }, { "confidence": "high", "disease": "Dystrophic cardiomyopathy", "glycan_involvement": "Glycosylation maintains complex integrity and function.", "mechanism": "Disruption of the glycoprotein complex in cardiac muscle leads to membrane instability, myocyte death, and fibrosis.", "protein": "Dystrophin-associated glycoprotein complex", "relationship_type": "causal", "source_pmcid": "PMC12653760" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin organizes glycoprotein complexes; loss indirectly affects glycosylation-dependent interactions.", "mechanism": "Genetic loss of dystrophin causes DMD.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12653760" }, { "confidence": "high", "disease": "Dystrophic cardiomyopathy", "glycan_involvement": "Disruption of glycoprotein complex affects glycan-mediated membrane stability.", "mechanism": "Absence of dystrophin in heart muscle leads to progressive cardiomyocyte loss and fibrosis.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12653760" }, { "confidence": "medium", "disease": "Dystrophic cardiomyopathy", "glycan_involvement": "Proper glycosylation is required for functional restoration.", "mechanism": "Restoration of the complex (via dystrophin replacement) is a therapeutic goal.", "protein": "Dystrophin-associated glycoprotein complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12653760" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Altered glycosylation patterns can indicate disease state.", "mechanism": "Loss or reduction of complex components is a diagnostic marker.", "protein": "Dystrophin-associated glycoprotein complex", "relationship_type": "biomarker", "source_pmcid": "PMC12653760" }, { "confidence": "high", "disease": "Meningitis", "glycan_involvement": "Catalyzes formation of CMP-sialic acid for glycan sialylation.", "mechanism": "CSS is essential for sialylation of NmB surface glycans, enabling immune evasion and virulence.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Meningitis", "glycan_involvement": "Terminal sialic acid residues on LOS are critical for immune evasion.", "mechanism": "Sialylated LOS protects NmB from complement-mediated killing and phagocytosis.", "protein": "Lipooligosaccharide (LOS)", "relationship_type": "causal", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Meningitis", "glycan_involvement": "\u03b12,8-linked polysialic acid forms the capsule structure.", "mechanism": "PolySia capsule mimics host neuronal glycans, aiding immune evasion and virulence.", "protein": "Capsular polysialic acid (polySia) capsule", "relationship_type": "causal", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Bacterial infection (Neisseria meningitidis)", "glycan_involvement": "Prevents formation of CMP-sialic acid, blocking glycan sialylation.", "mechanism": "Inhibition of CSS reduces sialylation of LOS, increasing bacterial susceptibility to immune attack.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Septicemia", "glycan_involvement": "Sialylation of LOS is required for full virulence.", "mechanism": "Sialylated LOS contributes to systemic dissemination and resistance to host defenses.", "protein": "Lipooligosaccharide (LOS)", "relationship_type": "causal", "source_pmcid": "PMC12654856" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "Enzyme required for sialylation of surface glycans.", "mechanism": "Presence/activity of CSS correlates with sialylation status and virulence of NmB.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Bacterial infection (Neisseria meningitidis)", "glycan_involvement": "Dense sialylation mimics host glycans.", "mechanism": "PolySia capsule shields bacteria from immune recognition.", "protein": "Capsular polysialic acid (polySia) capsule", "relationship_type": "protective", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Meningitis", "glycan_involvement": "Blocks sialylation of LOS and capsule.", "mechanism": "Neu5Ac\u03b22Me C-9 serine carboxamide inhibits CSS, reducing LOS sialylation and virulence.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654856" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "Sialylation status detectable by lectin binding.", "mechanism": "Level of LOS sialylation reflects CSS activity and bacterial virulence.", "protein": "Lipooligosaccharide (LOS)", "relationship_type": "biomarker", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Bacterial infection (Neisseria meningitidis)", "glycan_involvement": "Eliminates sialylation of surface glycans.", "mechanism": "Genetic knockout of CSS abolishes sialylation, leading to rapid bacterial killing by human serum.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654856" }, { "confidence": "high", "disease": "Zoonotic influenza", "glycan_involvement": "Direct binding to sialylated glycan receptors (\u03b12\u20133 and \u03b12\u20136 SA).", "mechanism": "tHA binds both \u03b12\u20133 (avian-type) and \u03b12\u20136 (human-type) sialic acid receptors, enabling potential cross-species transmission.", "protein": "Asiatic toad influenza-like virus hemagglutinin (tHA)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "high", "disease": "Zoonotic influenza", "glycan_involvement": "Binds GM2 ganglioside instead of sialylated glycan receptors.", "mechanism": "eHA does not bind canonical sialic acid receptors but binds GM2 ganglioside, suggesting a distinct host range and limited zoonotic potential.", "protein": "Spiny eel influenza-like virus hemagglutinin (eHA)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Direct binding to sialylated glycan receptors.", "mechanism": "IBV HA binds both \u03b12\u20133 and \u03b12\u20136 sialic acid receptors, mediating human and limited animal infection.", "protein": "Influenza B virus hemagglutinin (IBV HA)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Direct binding to sialylated glycan receptors.", "mechanism": "IAV H3N2 HA binds \u03b12\u20136 SA (human), InH5 HA binds \u03b12\u20133 SA (avian), determining host specificity.", "protein": "Influenza A virus hemagglutinin (IAV HA, H3N2, InH5)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Reovirus/rotavirus infection", "glycan_involvement": "GM2 ganglioside binding.", "mechanism": "eHA binds GM2 ganglioside, a receptor also used by some reoviruses and rotaviruses, indicating a shared glycan-mediated entry pathway.", "protein": "Spiny eel influenza-like virus hemagglutinin (eHA)", "relationship_type": "biomarker", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Zoonotic influenza", "glycan_involvement": "Binding to both \u03b12\u20133 and \u03b12\u20136 sialylated glycans.", "mechanism": "tHA\u2019s dual receptor specificity may facilitate adaptation to new hosts, but low thermal stability restricts transmission to warm-blooded animals.", "protein": "Asiatic toad influenza-like virus hemagglutinin (tHA)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Zoonotic influenza", "glycan_involvement": "Cleavage of sialic acid from host glycans.", "mechanism": "tNA exhibits canonical sialidase activity but is resistant to neuraminidase inhibitors, impacting antiviral treatment strategies.", "protein": "Asiatic toad influenza-like virus neuraminidase (tNA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Zoonotic influenza", "glycan_involvement": "Cleavage of sialic acid from host glycans.", "mechanism": "eNA has canonical sialidase activity but is sensitive to neuraminidase inhibitors.", "protein": "Spiny eel influenza-like virus neuraminidase (eNA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Zoonotic influenza", "glycan_involvement": "Glycan binding is necessary but not sufficient for cross-species infection.", "mechanism": "tHA\u2019s loose trimer packing and low thermostability may limit its ability to infect humans or birds at higher body temperatures.", "protein": "Asiatic toad influenza-like virus hemagglutinin (tHA)", "relationship_type": "causal", "source_pmcid": "PMC12654924" }, { "confidence": "medium", "disease": "Zoonotic influenza", "glycan_involvement": "Absence of canonical sialylated glycan binding.", "mechanism": "Lack of sialic acid receptor binding by eHA may act as a barrier to zoonotic transmission.", "protein": "Spiny eel influenza-like virus hemagglutinin (eHA)", "relationship_type": "protective", "source_pmcid": "PMC12654924" }, { "confidence": "high", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "Fiber protein glycosylation mediates host cell attachment and immune evasion.", "mechanism": "Adenovirus infection is associated with increased risk of severe outcomes (prolonged hospitalization, PICU admission) in immunocompromised pediatric cancer patients.", "protein": "Adenovirus Fiber Protein", "protein_enriched": { "function": "", "gene_name": "GIP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04146" }, "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "high", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "F glycoprotein N-glycosylation is essential for viral fusion and infectivity.", "mechanism": "RSV infection is linked to severe outcomes, especially in hematological malignancy patients.", "protein": "RSV Fusion Glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "medium", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "O-glycosylation of G protein modulates immune recognition.", "mechanism": "RSV G protein mediates viral attachment, contributing to pathogenesis in immunocompromised hosts.", "protein": "RSV Attachment Glycoprotein (G)", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "high", "disease": "Mortality", "glycan_involvement": "N-glycosylation affects fusion activity and immune response.", "mechanism": "RSV F protein implicated in the only mortality case (ALL patient) due to lower respiratory tract infection.", "protein": "RSV Fusion Glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "medium", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "Hemagglutinin glycosylation modulates host cell binding and antigenicity.", "mechanism": "Influenza is the most frequent virus detected, associated with severe outcomes.", "protein": "Influenza Hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "medium", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "Spike protein N-glycosylation shields epitopes from immune detection.", "mechanism": "SARS-CoV-2 infection not significantly associated with severe outcomes, but can disrupt cancer care.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "medium", "disease": "PICU Admission", "glycan_involvement": "Fusion glycoprotein glycosylation required for viral entry.", "mechanism": "HMPV infection implicated in PICU admission in immunocompromised children.", "protein": "Human Metapneumovirus Fusion Glycoprotein", "protein_enriched": { "function": "Inactive precursor that is cleaved to give rise to the mature F1 and F2 fusion glycoproteins", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q6WB98" }, "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "medium", "disease": "Severe Respiratory Viral Infection in Pediatric Cancer", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Parainfluenza detected in 19% of cases, associated with severe outcomes.", "protein": "Parainfluenza Hemagglutinin-Neuraminidase", "protein_enriched": { "function": "Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin l", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11227" }, "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "high", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "N-glycosylation critical for F protein function.", "mechanism": "RSV infection in ALL patient led to mortality, highlighting vulnerability.", "protein": "RSV Fusion Glycoprotein (F)", "relationship_type": "causal", "source_pmcid": "PMC12655028" }, { "confidence": "high", "disease": "Prolonged Hospitalization", "glycan_involvement": "Fiber protein glycosylation influences tissue tropism.", "mechanism": "Adenovirus infection predicts prolonged hospitalization in pediatric cancer patients.", "protein": "Adenovirus Fiber Protein", "protein_enriched": { "function": "", "gene_name": "GIP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04146" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655028" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Glycosylation modulates binding affinity and plasma half-life.", "mechanism": "Levels increase with age, affecting drug binding and pharmacokinetics.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12655055" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation state influences drug binding capacity.", "mechanism": "Elevated in HF, alters drug binding and disposition.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12655055" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may affect binding affinity for digoxin.", "mechanism": "Binds digoxin, modulating its free fraction and toxicity risk.", "protein": "Digoxin-binding glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12655055" }, { "confidence": "medium", "disease": "Drug Toxicity (Digoxin)", "glycan_involvement": "Glycosylation changes may alter drug binding and toxicity threshold.", "mechanism": "Altered glycoprotein levels change digoxin free fraction, impacting toxicity.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12655055" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Glycan structure modulates protective binding.", "mechanism": "Increased glycoprotein may buffer free drug levels, reducing acute toxicity.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12655055" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and ECM interactions.", "mechanism": "SMOC2 upregulation linked to cardiac disease progression via extracellular matrix remodeling.", "protein": "SMOC2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12655320" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Extracellular matrix glycoprotein; glycosylation likely modulates cell adhesion and signaling.", "mechanism": "High FREM1 expression involved in metabolism (bile acid, fatty acid, heme) and HF progression.", "protein": "FREM1", "protein_enriched": { "function": "", "gene_name": "1D", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6X5K3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12655320" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Ficolin family glycoprotein; glycosylation critical for ligand binding and immune function.", "mechanism": "FCN3 associated with inflammatory response and xenobiotic metabolism in HF.", "protein": "FCN3", "relationship_type": "biomarker", "source_pmcid": "PMC12655320" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects inhibitor activity and plasma stability.", "mechanism": "SERPINA3 linked to inflammation and adipogenesis in HF.", "protein": "SERPINA3", "protein_enriched": { "function": "Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2", "gene_name": "SERPINA3", "glycan_count": 192, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05724UK", "G06110VR", "G06247RL", "G08146BT", "G08918WF", "G11115RO", "G11629QQ", "G12793SR", "G13910DJ", "G15169WU", "G20312EM", "G22310AV", "G27947YN", "G31665QC", "G34617SM", "G39188ZX", "G39595FH", "G42358LZ", "G43669FQ", "G45495MK", "G47518TP", "G48414YA", "G49739MP", "G52527GH", "G52890YB", "G53075ES", "G59626AS", "G60033FS", "G64527OM", "G66088HZ", "G69834CE", "G70232NH", "G71146HJ", "G71560PC", "G74728JK", "G75983OB", "G77582RK", "G81637OR", "G84452RH", "G86795LJ", "G89205CJ", "G93656SY", "G93860XO", "G94917XT", "G95678HJ", "G99679NM", "G49108TO", "G00273SJ", "G04854VP", "G05962QB", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G20706XG", "G23010ZW", "G23863VK", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G28681TP", "G29545VG", "G30740WO", "G31028YV", "G31986NC", "G33791AF", "G36442WJ", "G37412TK", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41882MT", "G42962KI", "G43223CG", "G44215PV", "G44753VC", "G45395BF", "G46450MZ", "G46503DX", "G46691LC", "G46902YN", "G47737VJ", "G49018RC", "G50856PC", "G51413EV", "G54010QB", "G56518TU", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59324HL", "G59536GA", "G60834IK", "G63980BQ", "G64394MX", "G66282NU", "G68490OW", "G69521XL", "G70619PT", "G70888PK", "G71463BG", "G72747WU", "G72797UR", "G72951AH", "G75418YA", "G75568BH", "G77459ND", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81263BG", "G82443XX", "G82830MN", "G83229XP", "G84467IZ", "G85269DF", "G86182NS", "G86880BF", "G89877QI", "G90386IR", "G92081HT", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98611JV", "G99668VU", "G70418MS", "G88374WZ", "G07810QS", "G09700PF", "G09831WQ", "G10039CR", "G10488MI", "G11101UV", "G22572EH", "G29580WD", "G30221QT", "G31309XD", "G31852PQ", "G41044JW", "G43734MM", "G44211QA", "G45526EA", "G46665ZP", "G49755GI", "G50427EO", "G52848YE", "G56770VP", "G63040RU", "G64751KD", "G65344XH", "G66537LK", "G72309KR", "G74381CZ", "G78790NZ", "G81124ET", "G83213GG", "G84225JN", "G85144OK", "G87399DK", "G90789YQ", "G92275SC", "G92551JA", "G96577RX", "G57321FI", "G29068FM", "G43417UB", "G28622IK", "G33416PL", "G37692EO", "G39471UU", "G61256FT", "G63136LV", "G85282JO", "G85554PZ", "G94310CV", "G98129XB" ], "uniprot_id": "P01011" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655320" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy", "glycan_involvement": "Possible glycosylation may regulate STAT3 localization and activity.", "mechanism": "STAT3 phosphorylation (S727) promotes DCM; inhibition reduces cardiomyocyte injury.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12655320" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "TP53 dysregulation leads to apoptosis and adverse cardiac remodeling.", "protein": "TP53", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12655320" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "SRC overactivation drives maladaptive hypertrophy via MAPK/ERK and PI3K/AKT pathways.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12655320" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "GPCR glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "S1PR1 implicated in HF pathogenesis via GPCR signaling.", "protein": "S1PR1", "relationship_type": "causal", "source_pmcid": "PMC12655320" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Extracellular matrix glycoprotein; glycosylation may affect tissue integrity.", "mechanism": "LAD1 suggested as diagnostic biomarker for HF.", "protein": "LAD1", "relationship_type": "biomarker", "source_pmcid": "PMC12655320" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Possible glycoprotein; glycosylation may regulate nuclear localization.", "mechanism": "Differential HLTF expression associated with HF progression.", "protein": "HLTF", "protein_enriched": { "function": "Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of sp", "gene_name": "HLTF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14527" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655320" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "OLFM4 is a glycoprotein; glycosylation is essential for its stability and secretion.", "mechanism": "Serum OLFM4 levels are significantly elevated in asthma patients compared to healthy controls, correlating with disease severity and poor control.", "protein": "Olfactomedin 4 (OLFM4)", "protein_enriched": { "function": "May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apop", "gene_name": "OLFM4", "glycan_count": 56, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G27947YN", "G32788FZ", "G37818NZ", "G45395BF", "G45495MK", "G57776ZS", "G79666IR", "G84452RH", "G93718GY", "G05962QB", "G07810QS", "G23719VF", "G34989PA", "G39471UU", "G47644PP", "G63041LO", "G67164EE", "G70232NH", "G90659AW", "G11629QQ", "G15169WU", "G51413EV", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G59626AS", "G59924QI", "G92050GC", "G92406TI", "G95865ZB", "G04657PL", "G08290VR", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G22310AV", "G27126ED", "G29299MO", "G36013ES", "G46691LC", "G47950XN", "G70441OD", "G70619PT", "G81198YO", "G85269DF", "G35541EV", "G55132BD", "G75983OB", "G80075MS", "G95046LV" ], "uniprot_id": "Q6UX06" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655782" }, { "confidence": "high", "disease": "Severe Asthma", "glycan_involvement": "Glycosylation may modulate OLFM4's immune regulatory functions.", "mechanism": "OLFM4 levels increase with asthma severity and independently predict severe asthma.", "protein": "Olfactomedin 4 (OLFM4)", "protein_enriched": { "function": "May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apop", "gene_name": "OLFM4", "glycan_count": 56, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G27947YN", "G32788FZ", "G37818NZ", "G45395BF", "G45495MK", "G57776ZS", "G79666IR", "G84452RH", "G93718GY", "G05962QB", "G07810QS", "G23719VF", "G34989PA", "G39471UU", "G47644PP", "G63041LO", "G67164EE", "G70232NH", "G90659AW", "G11629QQ", "G15169WU", "G51413EV", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G59626AS", "G59924QI", "G92050GC", "G92406TI", "G95865ZB", "G04657PL", "G08290VR", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G22310AV", "G27126ED", "G29299MO", "G36013ES", "G46691LC", "G47950XN", "G70441OD", "G70619PT", "G81198YO", "G85269DF", "G35541EV", "G55132BD", "G75983OB", "G80075MS", "G95046LV" ], "uniprot_id": "Q6UX06" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655782" }, { "confidence": "high", "disease": "Neutrophilic Asthma", "glycan_involvement": "Glycosylation affects OLFM4's interaction with neutrophil granules and immune signaling.", "mechanism": "OLFM4 is linked to neutrophilic inflammation, a phenotype associated with severe and corticosteroid-resistant asthma.", "protein": "Olfactomedin 4 (OLFM4)", "protein_enriched": { "function": "May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apop", "gene_name": "OLFM4", "glycan_count": 56, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G27947YN", "G32788FZ", "G37818NZ", "G45395BF", "G45495MK", "G57776ZS", "G79666IR", "G84452RH", "G93718GY", "G05962QB", "G07810QS", "G23719VF", "G34989PA", "G39471UU", "G47644PP", "G63041LO", "G67164EE", "G70232NH", "G90659AW", "G11629QQ", "G15169WU", "G51413EV", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G59626AS", "G59924QI", "G92050GC", "G92406TI", "G95865ZB", "G04657PL", "G08290VR", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G22310AV", "G27126ED", "G29299MO", "G36013ES", "G46691LC", "G47950XN", "G70441OD", "G70619PT", "G81198YO", "G85269DF", "G35541EV", "G55132BD", "G75983OB", "G80075MS", "G95046LV" ], "uniprot_id": "Q6UX06" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655782" }, { "confidence": "medium", "disease": "Corticosteroid-resistant Asthma", "glycan_involvement": "Glycosylation may influence OLFM4's stability and immune modulation.", "mechanism": "Elevated OLFM4 is associated with corticosteroid resistance, possibly via neutrophil-mediated pathways.", "protein": "Olfactomedin 4 (OLFM4)", "protein_enriched": { "function": "May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apop", "gene_name": "OLFM4", "glycan_count": 56, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G27947YN", "G32788FZ", "G37818NZ", "G45395BF", "G45495MK", "G57776ZS", "G79666IR", "G84452RH", "G93718GY", "G05962QB", "G07810QS", "G23719VF", "G34989PA", "G39471UU", "G47644PP", "G63041LO", "G67164EE", "G70232NH", "G90659AW", "G11629QQ", "G15169WU", "G51413EV", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G59626AS", "G59924QI", "G92050GC", "G92406TI", "G95865ZB", "G04657PL", "G08290VR", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G22310AV", "G27126ED", "G29299MO", "G36013ES", "G46691LC", "G47950XN", "G70441OD", "G70619PT", "G81198YO", "G85269DF", "G35541EV", "G55132BD", "G75983OB", "G80075MS", "G95046LV" ], "uniprot_id": "Q6UX06" }, "relationship_type": "biomarker", "source_pmcid": "PMC12655782" }, { "confidence": "high", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "N- and O-glycosylation modulate receptor binding and immune evasion.", "mechanism": "HA mediates viral entry by binding to sialic acid receptors on host cells.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "high", "disease": "Vaccine mismatch (reduced vaccine effectiveness)", "glycan_involvement": "Glycosylation shields antigenic sites, facilitating immune escape.", "mechanism": "Amino acid substitutions in HA antigenic sites reduce antibody recognition, leading to vaccine mismatch.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "high", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "N-glycosylation affects enzymatic activity and antigenicity.", "mechanism": "NA enables viral release from host cells by cleaving sialic acids.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "medium", "disease": "Vaccine mismatch (reduced vaccine effectiveness)", "glycan_involvement": "Glycosylation changes may mask antigenic regions.", "mechanism": "Amino acid substitutions in NA alter antigenicity, contributing to vaccine mismatch.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "high", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "Glycosylation site patterns help distinguish circulating strains.", "mechanism": "HA sequence variation is used for molecular surveillance and strain identification.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12656348" }, { "confidence": "high", "disease": "Vaccine mismatch (reduced vaccine effectiveness)", "glycan_involvement": "Glycosylation can reduce antibody binding efficacy.", "mechanism": "HA is the primary target of neutralizing antibodies in vaccines.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656348" }, { "confidence": "medium", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "Glycosylation may influence drug binding and resistance.", "mechanism": "NA is targeted by antiviral drugs (e.g., oseltamivir).", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656348" }, { "confidence": "medium", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "Glycosylation modulates host specificity and pathogenicity.", "mechanism": "Mutations in HA1 domain alter receptor binding specificity and host range.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "medium", "disease": "Vaccine mismatch (reduced vaccine effectiveness)", "glycan_involvement": "Additional glycosylation shields antigenic epitopes.", "mechanism": "Novel N-glycosylation site in HA1 domain may contribute to antigenic drift and immune escape.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12656348" }, { "confidence": "medium", "disease": "Influenza A/H1N1pdm09 infection", "glycan_involvement": "Glycosylation site patterns help distinguish circulating strains.", "mechanism": "NA sequence variation is used for molecular surveillance and strain identification.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12656348" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "CPS is composed of serotype-specific polysaccharides with glycan epitopes.", "mechanism": "CPS is a major virulence factor enabling immune evasion and causing IPD.", "protein": "Capsular Polysaccharide (CPS) of Streptococcus pneumoniae", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "O-glycosylation of PsrP is required for its function.", "mechanism": "PsrP mediates adhesion to host cells, contributing to pneumococcal colonization and pneumonia.", "protein": "PsrP", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Adds \u03b11,3-linked galactose to polysaccharide chains.", "mechanism": "WCIN synthesizes \u03b1Gal epitopes on CPS, potentially affecting immune recognition.", "protein": "\u03b11,3-galactosyltransferase (WCIN)", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "high", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "Vaccine contains CPS with glycan epitopes, including \u03b1Gal.", "mechanism": "CPS is the antigenic target of PPV23 vaccine, inducing protective antibodies.", "protein": "Capsular Polysaccharide (CPS) of Streptococcus pneumoniae", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "\u03b1Gal is a glycan motif recognized by natural antibodies.", "mechanism": "Induces anti-Gal antibodies that may enhance immune clearance of S. pneumoniae.", "protein": "\u03b1Gal epitope on CPS", "relationship_type": "protective", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Glycosylation pattern determines immune evasion.", "mechanism": "CPS enables bloodstream invasion by resisting phagocytosis.", "protein": "Capsular Polysaccharide (CPS) of Streptococcus pneumoniae", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "Serotype-specific glycan structures are implicated.", "mechanism": "CPS facilitates crossing of blood-brain barrier and immune evasion.", "protein": "Capsular Polysaccharide (CPS) of Streptococcus pneumoniae", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Vaccine response variability", "glycan_involvement": "\u03b1Gal glycan motif is the target of natural antibodies.", "mechanism": "Pre-existing anti-Gal antibody levels modulate PPV23 vaccine response.", "protein": "\u03b1Gal epitope on CPS", "relationship_type": "biomarker", "source_pmcid": "PMC12656782" }, { "confidence": "medium", "disease": "Invasive Pneumococcal Disease (IPD)", "glycan_involvement": "O-glycosylation is essential for PsrP function.", "mechanism": "Glycosylated PsrP enhances bacterial adhesion and virulence.", "protein": "PsrP", "relationship_type": "causal", "source_pmcid": "PMC12656782" }, { "confidence": "low", "disease": "Pneumonia", "glycan_involvement": "\u03b1Gal is a glycan epitope recognized by host antibodies.", "mechanism": "Anti-Gal antibodies may promote opsonization and clearance of pneumococci.", "protein": "\u03b1Gal epitope on CPS", "relationship_type": "protective", "source_pmcid": "PMC12656782" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Contains at least one N-linked glycosylation site, which may affect folding, immune evasion, and antigenicity.", "mechanism": "Gn mediates viral entry and release from host cells, essential for infection.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Contains 3\u20134 potential N-linked glycosylation sites, influencing host cell interaction and immune recognition.", "mechanism": "Gc mediates viral attachment, membrane fusion, and is critical for viral entry and pathogenesis.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Glycosylation may enhance antigenicity and stability as a diagnostic target.", "mechanism": "Surface-exposed, immunogenic; contains B-cell and T-cell epitopes suitable for serological diagnostics.", "protein": "Gn glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Glycosylation may stabilize epitopes and affect antibody recognition.", "mechanism": "Surface-exposed, immunogenic; contains conserved B-cell epitopes used in diagnostics.", "protein": "Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12656799" }, { "confidence": "medium", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "N-glycosylation may modulate immunogenicity and vaccine efficacy.", "mechanism": "Overlapping B-cell and T-cell epitopes make Gn a promising vaccine candidate.", "protein": "Gn glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "N-glycosylation sites may affect epitope exposure and immune response.", "mechanism": "Contains conserved, surface-exposed B-cell epitopes; targeted by neutralizing antibodies in vaccine studies.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Glycosylation may enhance immunogenicity and vaccine-induced protection.", "mechanism": "Vaccination with Gc induces strong neutralizing antibody response and reduces viral load in animal models.", "protein": "Gc glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "Glycosylation may stabilize diagnostic epitopes.", "mechanism": "Conserved B-cell epitope identified as reliable for diagnostic assay development.", "protein": "Gc glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12656799" }, { "confidence": "medium", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "N-glycosylation may influence immune recognition.", "mechanism": "Elicits both humoral and cellular immune responses, supporting its use in vaccines.", "protein": "Gn glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Oropouche virus disease (Oropouche fever / sloth fever)", "glycan_involvement": "High level of N-glycosylation increases immunogenicity and functional importance.", "mechanism": "Extensive post-translational modifications (including glycosylation) enhance its role as a vaccine target.", "protein": "Gc glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656799" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Mediates membrane fusion and viral entry into host cells.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "causal", "source_pmcid": "PMC12656802" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation influences receptor binding and immunogenicity.", "mechanism": "Binds to host ephrin-B2/B3 receptors, triggering entry.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC12656802" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "Target for neutralizing antibodies and vaccine-induced protection.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656802" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Target for vaccine-induced immune responses.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656802" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation may modulate vaccine efficacy.", "mechanism": "Vaccination with NiV-G induces protective immunity in mice.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "protective", "source_pmcid": "PMC12656802" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation status used to distinguish precursor and cleaved forms.", "mechanism": "Detection of NiV-F in pseudovirus confirms viral entry machinery.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "biomarker", "source_pmcid": "PMC12656802" }, { "confidence": "medium", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Presence of NiV-G on pseudovirus surface used for neutralization assays.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "biomarker", "source_pmcid": "PMC12656802" }, { "confidence": "medium", "disease": "Nipah virus encephalitis", "glycan_involvement": "Glycosylation required for functional protein.", "mechanism": "Facilitates viral spread to the brain via membrane fusion.", "protein": "Nipah virus fusion glycoprotein F", "protein_enriched": { "function": "Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q9IH62" }, "relationship_type": "causal", "source_pmcid": "PMC12656802" }, { "confidence": "medium", "disease": "Nipah virus respiratory illness", "glycan_involvement": "Glycosylation modulates tropism.", "mechanism": "Initiates infection in respiratory epithelial cells.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC12656802" }, { "confidence": "high", "disease": "Nipah virus infection", "glycan_involvement": "Glycosylation impacts antibody accessibility.", "mechanism": "Commercial anti-NiV-G antibody robustly neutralizes pseudovirus infection.", "protein": "Nipah virus attachment glycoprotein G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12656802" }, { "confidence": "high", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation enables receptor binding and membrane fusion.", "mechanism": "Mediates host cell invasion and initiates infection cascade.", "protein": "gK", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Cell-to-cell viral transmission", "glycan_involvement": "Glycosylation modulates antigenic epitope presentation and immune evasion.", "mechanism": "Essential for membrane fusion and spread between host cells.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation critical for specialized binding domains.", "mechanism": "Facilitates host cell invasion and enhances viral virulence.", "protein": "gC", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Glycosylation maintains envelope integrity.", "mechanism": "Stabilizes virion envelope and confers resistance to \u03b2-defensin-mediated permeabilization.", "protein": "gM", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Glycosylation required for chemokine-binding activity.", "mechanism": "Binds and neutralizes chemokines (e.g., IL-8), dampening immune cell migration.", "protein": "gG", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Endothelial cell infection", "glycan_involvement": "Glycosylation affects receptor binding specificity.", "mechanism": "Mediates entry into equine cells via interaction with MHC-I.", "protein": "gD", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Cell-to-cell viral transmission", "glycan_involvement": "Glycosylation supports cell junction targeting.", "mechanism": "Facilitates intercellular spread, bypassing extracellular immune recognition.", "protein": "gE/gI", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Viremia", "glycan_involvement": "Glycosylation masks antigenic sites.", "mechanism": "Restricted expression in infected leukocytes protects from antibody recognition.", "protein": "gC/gD", "relationship_type": "immune evasion", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Abortion", "glycan_involvement": "Glycosylation required for cell adhesion and fusion.", "mechanism": "Mediates viral transfer from leukocytes to uterine endothelial cells, triggering vasculitis and thrombosis.", "protein": "gB/gC/gD", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "Equine herpesvirus myeloencephalopathy (EHM)", "glycan_involvement": "Glycosylation modulates tropism and immune escape.", "mechanism": "Facilitates CNS endothelial infection, vasculitis, and thrombosis.", "protein": "gB/gC/gD/gM", "relationship_type": "causal", "source_pmcid": "PMC12656896" }, { "confidence": "high", "disease": "CDG-Ie", "glycan_involvement": "Defective synthesis of dolichol-phosphate-mannose affects N- and O-glycosylation.", "mechanism": "Mutations in DPM1 reduce DPM transferase activity, impairing glycosylation pathways.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy (\u03b1-DGP)", "glycan_involvement": "Impaired O-glycosylation of \u03b1-DG leads to muscle weakness and elevated creatine kinase.", "mechanism": "DPM1 mutations disrupt O-glycosylation of \u03b1-DG, compromising muscle membrane integrity.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "high", "disease": "Alpha-dystroglycanopathy (\u03b1-DGP)", "glycan_involvement": "Defective O-glycosylation impairs extracellular matrix binding.", "mechanism": "Hypoglycosylation of \u03b1-DG results in progressive muscle weakness and atrophy.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "high", "disease": "CDG-Ie", "glycan_involvement": "Mutations detected by sequencing indicate glycosylation defects.", "mechanism": "Genetic variants in DPM1 serve as diagnostic markers for CDG-Ie.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12657098" }, { "confidence": "high", "disease": "CDG-Ie", "glycan_involvement": "Global impairment of N- and O-glycosylation in multiple tissues.", "mechanism": "DPM1 deficiency leads to multisystem involvement (neurological, hepatic, muscular).", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "medium", "disease": "CDG-Ie", "glycan_involvement": "Reduced donor substrate availability for glycosylation.", "mechanism": "Defective DPM1 affects GPI anchoring and C-mannosylation.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "medium", "disease": "CDG-Ie", "glycan_involvement": "O-glycosylation defect in \u03b1-DG.", "mechanism": "Elevated creatine kinase reflects muscle membrane instability due to \u03b1-DG hypoglycosylation.", "protein": "Alpha-dystroglycan (\u03b1-DG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12657098" }, { "confidence": "medium", "disease": "CDG-Ie", "glycan_involvement": "Defective N- and O-glycosylation in neural tissues.", "mechanism": "DPM1 mutations cause neurological symptoms via impaired glycosylation in the nervous system.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "medium", "disease": "CDG-Ie", "glycan_involvement": "Impaired glycosylation of liver proteins.", "mechanism": "DPM1 deficiency leads to hepatic dysfunction due to glycosylation defects.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "low", "disease": "CDG-Ie", "glycan_involvement": "Potential impact on glycoproteins in auditory pathways.", "mechanism": "DPM1 mutations may contribute to hearing abnormalities via glycosylation defects.", "protein": "DPM1", "protein_enriched": { "function": "Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylino", "gene_name": "DPM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60762" }, "relationship_type": "causal", "source_pmcid": "PMC12657098" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Altered N-glycosylation disrupts TMEM59 function.", "mechanism": "Downregulated in AD; involved in glycoprotein maturation and trafficking, affecting protein-folding quality control.", "protein": "TMEM59", "protein_enriched": { "function": "", "gene_name": "SPATC1L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0A9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Binds aberrant N-glycans, indicating glycoprotein misfolding.", "mechanism": "Upregulated in AD; ER lectin recognizing misfolded glycoproteins, reflecting ER stress response.", "protein": "MLEC", "protein_enriched": { "function": "Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS) (PubMed:30442762, PubMed:30442766, P", "gene_name": "LZTR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Controls expression of glycosylation pathway genes.", "mechanism": "Upregulated in AD; regulates N-glycosylation genes and glial activation.", "protein": "MAX", "protein_enriched": { "function": "Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, w", "gene_name": "MAX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P61244" }, "relationship_type": "biomarker/central transcriptional regulator", "source_pmcid": "PMC12657396" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP cleavage and aggregation.", "mechanism": "Key AD molecule; N-glycosylation affects APP processing and amyloid-beta generation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Alters N-glycan branching, affecting protein function and aggregation.", "mechanism": "Regulates bisecting GlcNAc formation; implicated in AD-related glycan changes.", "protein": "MGAT3 (GNT-III)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Initiates N-glycosylation of nascent proteins.", "mechanism": "N-glycosylation transferase; associated with TMEM59 and AD pathology.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Completes N-glycosylation post-translationally.", "mechanism": "N-glycosylation transferase; correlated with TMEM59 and APP in AD.", "protein": "STT3B", "protein_enriched": { "function": "May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Binds preferentially to methylated DNA (PubMed:28473536)", "gene_name": "LHX4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q969G2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Binds monoglucosylated N-glycans during protein folding.", "mechanism": "ER chaperone; assists folding of N-glycosylated proteins, implicated in AD.", "protein": "CALR", "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Interacts with N-glycans during folding.", "mechanism": "ER chaperone; involved in glycoprotein folding and quality control in AD.", "protein": "CANX", "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects CTSD stability and function.", "mechanism": "Lysosomal glycoprotein; involved in protein degradation, altered in AD.", "protein": "CTSD", "relationship_type": "biomarker", "source_pmcid": "PMC12657396" }, { "confidence": "high", "disease": "Urinary tract infection", "glycan_involvement": "FimH binds \u03b1-D-mannose on host N-linked glycans.", "mechanism": "FimH mediates E. coli adhesion to host cells via glycan binding, facilitating infection.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "causal", "source_pmcid": "PMC12658034" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "FimH binds host cell surface glycans.", "mechanism": "FimH acts as a virulence factor in E. coli, promoting adhesion and inflammation.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "causal", "source_pmcid": "PMC12658034" }, { "confidence": "high", "disease": "Urinary tract infection", "glycan_involvement": "Antibody N-glycan mimics host glycan, competitively inhibiting FimH.", "mechanism": "Antibodies (e.g., mAb475) and glycan-mimetic compounds block FimH-mediated adhesion.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658034" }, { "confidence": "high", "disease": "Diffuse large B-cell lymphoma", "glycan_involvement": "N-glycosylation at Asn90 on Fab CDR3.", "mechanism": "High-mannose N-glycosylation on antibody hypervariable loops is associated with lymphoma.", "protein": "IgG (antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC12658034" }, { "confidence": "medium", "disease": "Diffuse large B-cell lymphoma", "glycan_involvement": "High-mannose N-glycans on CDRs facilitate lectin binding.", "mechanism": "Microbial lectins (e.g., FimH) interact with high-mannose glycosylated B-cell receptors, promoting tumor cell persistence.", "protein": "B-cell receptor (Fab fragment)", "relationship_type": "causal", "source_pmcid": "PMC12658034" }, { "confidence": "medium", "disease": "Follicular lymphoma", "glycan_involvement": "N-glycosylation on CDRs.", "mechanism": "Presence of N-glycosylation on hypervariable loops is characteristic of follicular lymphoma.", "protein": "B-cell receptor (Fab fragment)", "relationship_type": "biomarker", "source_pmcid": "PMC12658034" }, { "confidence": "medium", "disease": "Burkitt\u2019s lymphoma", "glycan_involvement": "High-mannose N-glycans on CDRs.", "mechanism": "N-glycosylation on Fab CDRs is associated with Burkitt\u2019s lymphoma.", "protein": "B-cell receptor (Fab fragment)", "relationship_type": "biomarker", "source_pmcid": "PMC12658034" }, { "confidence": "low", "disease": "Autoimmune disorders", "glycan_involvement": "Induced N-glycosylation on CDRs.", "mechanism": "Microbial antigens can trigger B-cell receptor glycosylation, contributing to autoimmunity.", "protein": "B-cell receptor (Fab fragment)", "relationship_type": "causal", "source_pmcid": "PMC12658034" }, { "confidence": "medium", "disease": "Diffuse large B-cell lymphoma", "glycan_involvement": "FimH binds high-mannose N-glycans on B-cell receptors.", "mechanism": "FimH and other microbial lectins may trigger selection of high-mannose glycosylated B-cell receptors, initiating lymphoma development.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "causal", "source_pmcid": "PMC12658034" }, { "confidence": "high", "disease": "Urinary tract infection", "glycan_involvement": "Antibody binding alters FimH glycan interaction.", "mechanism": "Antibodies (e.g., mAb926, mAb824, mAb21) modulate FimH conformation and block adhesion.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658034" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation is required for Fetuin-A secretion and function.", "mechanism": "Fetuin-A inhibits insulin receptor signaling, aggravates insulin resistance, and is an independent risk factor for T2D.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12658064" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects Fetuin-A stability and hepatokine activity.", "mechanism": "Elevated Fetuin-A is associated with hepatic steatosis and inflammation, contributing to MASLD pathogenesis.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12658064" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation modulates Fetuin-A's interaction with liver cells.", "mechanism": "High Fetuin-A levels correlate with liver fibrosis; reduction is associated with improved fibrosis.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12658064" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation is essential for Fetuin-A's inhibitory function.", "mechanism": "Fetuin-A inhibits insulin receptor tyrosine kinase, promoting insulin resistance.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12658064" }, { "confidence": "medium", "disease": "Pancreatic beta cell dysfunction", "glycan_involvement": "Glycosylation influences Fetuin-A secretion from beta cells.", "mechanism": "Fetuin-A secreted from beta cells increases macrophage migration and beta cell inflammation, leading to dysfunction and apoptosis.", "protein": "Fetuin-A", "relationship_type": "causal", "source_pmcid": "PMC12658064" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Therapeutic modulation may affect glycosylation-dependent secretion.", "mechanism": "Lowering Fetuin-A (via Metformin or Dapagliflozin) improves insulin sensitivity and glycemic control.", "protein": "Fetuin-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658064" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation status may influence drug efficacy on Fetuin-A.", "mechanism": "Reduction of Fetuin-A by Metformin or Dapagliflozin may ameliorate hepatic steatosis and inflammation.", "protein": "Fetuin-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658064" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation may affect Fetuin-A's fibrogenic activity.", "mechanism": "Metformin and Dapagliflozin reduce Fetuin-A, associated with decreased hepatic fibrosis.", "protein": "Fetuin-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658064" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation-dependent secretion targeted by drugs.", "mechanism": "Lowering Fetuin-A improves insulin sensitivity.", "protein": "Fetuin-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658064" }, { "confidence": "medium", "disease": "Pancreatic beta cell dysfunction", "glycan_involvement": "Glycosylation influences Fetuin-A's beta cell effects.", "mechanism": "Reduction of Fetuin-A may protect beta cells from inflammation and apoptosis.", "protein": "Fetuin-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658064" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation at multiple sites (N35, N192, N200, N219) stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 expression and glycosylation status predict response to anti-PD-1 therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658286" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation at N219 of PD-L1 mediated by GALNT16.", "mechanism": "GALNT16 upregulates PD-L1 glycosylation at N219, increasing PD-L1 stability and promoting immune escape.", "protein": "GALNT16", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658286" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Indirectly promotes N-glycosylation of PD-L1 via GALNT16.", "mechanism": "YY1 transcriptionally upregulates GALNT16, leading to increased PD-L1 glycosylation and resistance to anti-PD-1 therapy.", "protein": "YY1", "relationship_type": "causal", "source_pmcid": "PMC12658286" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Likely similar N-glycosylation mechanism as in HCC.", "mechanism": "High YY1 expression correlates with poor survival in melanoma patients treated with anti-PD-1 therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658286" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Likely similar N-glycosylation mechanism as in HCC.", "mechanism": "High YY1 expression correlates with poor survival in glioblastoma patients treated with anti-PD-1 therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658286" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "N-glycosylation of PD-L1.", "mechanism": "B4GALT1 catalyzes N-glycosylation of PD-L1, stabilizing PD-L1 and promoting immune evasion.", "protein": "B4GALT1", "relationship_type": "causal", "source_pmcid": "PMC12658286" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation of PD-L1.", "mechanism": "B3GNT3 enhances PD-L1 glycosylation, increasing its stability and immunosuppressive function.", "protein": "B3GNT3", "protein_enriched": { "function": "Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference fo", "gene_name": "B3GNT2", "glycan_count": 25, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G62765YT", "G80920RR", "G83460ZZ", "G85282JO", "G56784JY", "G27058EU", "G82348BZ", "G83633GK", "G22573RC", "G22768VO", "G25418HZ", "G31852PQ", "G42227JK", "G70101JE", "G81315DD", "G06356OH", "G33791AF", "G48414YA", "G86795LJ", "G57321FI", "G04854VP", "G63980BQ", "G75983OB", "G94470IW" ], "uniprot_id": "Q9NY97" }, "relationship_type": "causal", "source_pmcid": "PMC12658286" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation of PD-L1.", "mechanism": "IL-6/JAK1-driven phosphorylation recruits STT3A to catalyze PD-L1 glycosylation, sustaining PD-L1 stability.", "protein": "STT3A", "protein_enriched": { "function": "Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophos", "gene_name": "STT3B", "glycan_count": 47, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G01650EU", "G23294PN", "G31852PQ", "G32577BC", "G37399XV", "G46503DX", "G46524LG", "G51653BI", "G62765YT", "G62894KT", "G70101JE", "G73430PD", "G80920RR", "G82463GQ", "G83460ZZ", "G92050GC", "G02815KT", "G08290VR", "G14260UH", "G15664MX", "G25079LO", "G36442WJ", "G40834TG", "G40926MX", "G41247ZX", "G46902YN", "G48584BU", "G49642SA", "G54010QB", "G59626AS", "G64527OM", "G66621EA", "G72747WU", "G78649WQ", "G79568CQ", "G83633GK", "G83646BJ", "G84862VB", "G85554PZ", "G90659AW", "G96430BV", "G81980VO", "G05724UK", "G39188ZX", "G50282JC", "G92406TI" ], "uniprot_id": "Q8TCJ2" }, "relationship_type": "causal", "source_pmcid": "PMC12658286" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation impairs antibody recognition and promotes immune escape.", "mechanism": "Hyper-glycosylated PD-L1 resists anti-PD-1 therapy; deglycosylation increases antibody binding and efficacy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12658286" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation at N219 of PD-L1.", "mechanism": "High GALNT16 expression correlates with high PD-L1 glycosylation and poor response to immunotherapy.", "protein": "GALNT16", "relationship_type": "biomarker", "source_pmcid": "PMC12658286" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "YKL40 is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "CSF YKL40 is increased in AD, reflecting neuroinflammation and microglial activation.", "protein": "YKL40", "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "high", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation required for function; not a useful biomarker in DLB.", "mechanism": "CSF YKL40 is not elevated in DLB or MCI-LB compared to controls.", "protein": "YKL40", "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "TREM2 is N-glycosylated, which affects its cell surface expression and shedding.", "mechanism": "Genetic variants and increased soluble TREM2 in CSF are associated with AD risk and microglial response.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12658555" }, { "confidence": "high", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation influences shedding and detection in CSF.", "mechanism": "Soluble TREM2 is not elevated in DLB unless AD pathology co-exists.", "protein": "Soluble TREM2", "protein_enriched": { "function": "", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZC2-2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation is required for secretion and function.", "mechanism": "CSF progranulin is not elevated in DLB unless AD pathology is present.", "protein": "Progranulin", "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CRP is heavily glycosylated; glycosylation affects its stability and function.", "mechanism": "High plasma CRP is associated with increased risk of memory and visuospatial impairment.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect solubility.", "mechanism": "GFAP is elevated in MCI-AD, reflecting astrocytic activation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation may modulate GFAP function.", "mechanism": "GFAP is elevated in LBD, indicating astrocytic response.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "IL-6 is glycosylated, which is important for secretion.", "mechanism": "Peripheral and CSF IL-6 levels are variably associated with AD; higher levels linked to worse cognition.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "medium", "disease": "Dementia with Lewy bodies (DLB)", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Peripheral IL-6 levels are variably increased in DLB; higher levels associated with worse cognition.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658555" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "AQP4 localization depends on glycoprotein complexes (dystroglycan/agrin); glycosylation affects membrane anchoring.", "mechanism": "AQP4 upregulation and mislocalization drive GBM progression by promoting cell migration, invasion, edema, immune evasion, and therapy resistance.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12658779" }, { "confidence": "high", "disease": "Peritumoral edema", "glycan_involvement": "Glycosylation of anchoring proteins affects AQP4 polarization.", "mechanism": "Disorganized and upregulated AQP4 disrupts osmotic gradients, leading to fluid accumulation and edema.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12658779" }, { "confidence": "high", "disease": "Blood\u2013brain barrier (BBB) disruption", "glycan_involvement": "Dystroglycan glycosylation is critical for AQP4 anchoring at astrocytic endfeet.", "mechanism": "Loss of AQP4 polarity and anchoring degrades BBB integrity, increasing permeability.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12658779" }, { "confidence": "medium", "disease": "Immune evasion in GBM", "glycan_involvement": "Indirect; glycosylation of AQP4 complexes may affect immune cell interactions.", "mechanism": "AQP4 upregulation promotes M2-like macrophage polarization, creating an immunosuppressive tumor microenvironment.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12658779" }, { "confidence": "medium", "disease": "Therapy resistance in GBM", "glycan_involvement": "Not directly specified.", "mechanism": "AQP4 supports survival of therapy-resistant, stem-like glioma cells in hypoxic niches.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12658779" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Not directly specified.", "mechanism": "AQP4 isoform balance (M1 vs. M23) correlates with invasive vs. apoptotic phenotypes in GBM.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC12658779" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N- and O-glycosylation of dystroglycan is essential for AQP4 localization.", "mechanism": "Degradation or altered glycosylation of dystroglycan disrupts AQP4 anchoring, contributing to BBB breakdown and edema.", "protein": "Dystroglycan", "protein_enriched": { "function": "The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cel", "gene_name": "DAG1", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G80920RR", "G57321FI", "G53434XO", "G49108TO", "G29068FM", "G29931IJ", "G43417UB", "G29209BS", "G81124ET", "G50947IE", "G05724UK", "G14260UH", "G37399XV", "G39188ZX", "G62894KT", "G64527OM", "G70101JE", "G70696MD", "G80333GO", "G82119TF", "G82463GQ", "G85269DF" ], "uniprot_id": "Q14118" }, "relationship_type": "causal", "source_pmcid": "PMC12658779" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Agrin is a heparan sulfate proteoglycan; glycan chains mediate interactions.", "mechanism": "Loss of agrin impairs AQP4 anchoring, affecting BBB and glymphatic function.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC12658779" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorders (NMOSD)", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "AQP4 is the autoantigen in NMOSD; anti-AQP4 antibodies mediate disease.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12658779" }, { "confidence": "low", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Not specified.", "mechanism": "AQP3 is upregulated at the migrating edge of cancer cells in response to chemokine CXCL12, promoting invasion.", "protein": "Aquaporin-3 (AQP3)", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:122", "gene_name": "AQP3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q92482" }, "relationship_type": "causal", "source_pmcid": "PMC12658779" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "GlycA measures N-acetyl groups on acute-phase glycoproteins (mainly \u03b11-acid glycoprotein, haptoglobin, \u03b11-antitrypsin, \u03b11-antichymotrypsin, transferrin); glycosylation status affects inflammatory signaling.", "mechanism": "Reflects systemic inflammation; higher GlycA associated with increased COPD risk.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "high", "disease": "Impaired Lung Function", "glycan_involvement": "Reflects glycosylation of acute-phase proteins; altered glycosylation linked to inflammation and tissue remodeling.", "mechanism": "Higher GlycA levels inversely associated with FEV1 and FVC.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "N-acetyl glycan groups on plasma glycoproteins modulate inflammatory pathways.", "mechanism": "Associated with systemic inflammation and increased diabetes risk.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation of acute-phase proteins influences immune response.", "mechanism": "Elevated GlycA reflects chronic inflammation in RA.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation of plasma proteins modulates vascular inflammation.", "mechanism": "Higher GlycA predicts increased cardiovascular risk and mortality.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) with N-glycosylation affecting function.", "mechanism": "Higher sHDL inversely associated with COPD risk; sHDL has anti-inflammatory properties.", "protein": "Small High-Density Lipoprotein particles (sHDL)", "relationship_type": "protective", "source_pmcid": "PMC12659030" }, { "confidence": "high", "disease": "Impaired Lung Function", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-inflammatory and surfactant-inducing effects.", "mechanism": "Higher sHDL positively associated with FEV1 and FVC; may stimulate surfactant production.", "protein": "Small High-Density Lipoprotein particles (sHDL)", "relationship_type": "protective", "source_pmcid": "PMC12659030" }, { "confidence": "medium", "disease": "All-cause and Cancer Mortality", "glycan_involvement": "Reflects systemic glycosylation changes in acute-phase proteins.", "mechanism": "Elevated GlycA predicts increased mortality risk.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "low", "disease": "Depression", "glycan_involvement": "Glycosylation of plasma proteins influences neuroinflammatory pathways.", "mechanism": "Higher GlycA associated with increased risk of depression via chronic inflammation.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12659030" }, { "confidence": "medium", "disease": "Impaired Lung Function", "glycan_involvement": "Altered glycosylation of acute-phase proteins drives inflammatory and fibrotic processes.", "mechanism": "Chronic inflammation reflected by GlycA may contribute to airway remodeling and fibrosis.", "protein": "Glycoprotein Acetyls (GlycA)", "relationship_type": "causal (suggested)", "source_pmcid": "PMC12659030" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2; O. ramonense metabolites (e.g., alpha-tocopherol acetate, thymol, vanillic acid) show binding and potential inhibition.", "protein": "SARS-CoV Spike Glycoprotein", "protein_enriched": { "function": "May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity", "gene_name": "S", "glycan_count": 17, "glycosylation_sites_count": 23, "glytoucan_ids": [ "G20956ZV", "G57317CE", "G62765YT", "G80475RE", "G80920RR", "G93579XB", "G25987BV", "G28681TP", "G31852PQ", "G35029YA", "G41247ZX", "G02815KT", "G92050GC", "G10339FR", "G16407EV", "G53434XO", "G82364UA" ], "uniprot_id": "P59594" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12660920" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates fusion and immune evasion.", "mechanism": "S2 subunit mediates membrane fusion; plant metabolites dock to S2, potentially inhibiting fusion.", "protein": "SARS-CoV-2 S2 Subunit", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12660920" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein but may interact with glycosylated viral proteins.", "mechanism": "Mpro is essential for viral replication; O. ramonense metabolites bind and may inhibit protease activity.", "protein": "SARS-CoV Main Protease (Mpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12660920" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "ER\u03b1 is N-glycosylated, affecting receptor stability and signaling.", "mechanism": "Caffeic acid and other polyphenols bind ER\u03b1, potentially inhibiting estrogen-driven proliferation.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12660920" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Aromatase is N-glycosylated, influencing enzyme activity.", "mechanism": "Caffeic acid inhibits aromatase, reducing estrogen synthesis.", "protein": "Cytochrome P450 Aromatase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12660920" }, { "confidence": "low", "disease": "Bacterial Infections (S. aureus, S. pneumoniae)", "glycan_involvement": "Glycosphingolipids mediate host-pathogen interactions via glycan moieties.", "mechanism": "Plant-derived metabolites may disrupt bacterial adhesion to host glycosphingolipids, reducing infection.", "protein": "Glycosphingolipids (cell surface)", "relationship_type": "protective", "source_pmcid": "PMC12660920" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans affect antigenicity and immune recognition.", "mechanism": "Spike glycoprotein is used for diagnosis and as a vaccine antigen.", "protein": "SARS-CoV Spike Glycoprotein", "protein_enriched": { "function": "May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity", "gene_name": "S", "glycan_count": 17, "glycosylation_sites_count": 23, "glytoucan_ids": [ "G20956ZV", "G57317CE", "G62765YT", "G80475RE", "G80920RR", "G93579XB", "G25987BV", "G28681TP", "G31852PQ", "G35029YA", "G41247ZX", "G02815KT", "G92050GC", "G10339FR", "G16407EV", "G53434XO", "G82364UA" ], "uniprot_id": "P59594" }, "relationship_type": "biomarker", "source_pmcid": "PMC12660920" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates infectivity and immune evasion.", "mechanism": "Spike glycoprotein is essential for viral infectivity.", "protein": "SARS-CoV Spike Glycoprotein", "protein_enriched": { "function": "May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity", "gene_name": "S", "glycan_count": 17, "glycosylation_sites_count": 23, "glytoucan_ids": [ "G20956ZV", "G57317CE", "G62765YT", "G80475RE", "G80920RR", "G93579XB", "G25987BV", "G28681TP", "G31852PQ", "G35029YA", "G41247ZX", "G02815KT", "G92050GC", "G10339FR", "G16407EV", "G53434XO", "G82364UA" ], "uniprot_id": "P59594" }, "relationship_type": "causal", "source_pmcid": "PMC12660920" }, { "confidence": "low", "disease": "Breast Cancer", "glycan_involvement": "Aberrant glycosylation modulates cancer cell interactions.", "mechanism": "Altered glycosphingolipid expression affects cell signaling and tumor progression.", "protein": "Glycosphingolipids (cell surface)", "relationship_type": "causal", "source_pmcid": "PMC12660920" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation may affect receptor detection.", "mechanism": "ER\u03b1 status guides therapy selection.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "biomarker", "source_pmcid": "PMC12660920" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "Laminin-\u03b12 is a glycoprotein; proper glycosylation is essential for its ECM function.", "mechanism": "Loss-of-function mutations in LAMA2 gene lead to absence of laminin-\u03b12, causing muscle fiber degeneration, inflammation, and fibrosis.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Glycosylation of laminin-\u03b12 is necessary for its secretion and ECM integration.", "mechanism": "MuSC-derived laminin-\u03b12 is required for muscle stem cell proliferation and expansion during regeneration; its absence delays regeneration.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "medium", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "Therapeutic strategies may need to ensure correct glycosylation for functional protein.", "mechanism": "Restoring laminin-\u03b12 or its function in MuSCs may improve muscle regeneration and slow disease progression.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "Detection methods often rely on glycosylated epitopes.", "mechanism": "Absence of laminin-\u03b12 in muscle biopsies is diagnostic for LAMA2 MD.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Loss of glycosylated laminin-\u03b12 from MuSCs disrupts ECM remodeling.", "mechanism": "MuSC-specific knockout of Lama2 is sufficient to slow MuSC proliferation and delay muscle regeneration.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "Glycosylation status affects protein stability and function.", "mechanism": "Laminin-\u03b12 deficiency in MuSCs impairs cell-cycle progression of myogenic precursors, contributing to disease pathology.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Proper glycosylation required for ECM deposition and MuSC niche function.", "mechanism": "Laminin-\u03b12-deficient MuSCs fail to expand after injury, leading to delayed muscle repair.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "MuSC-secreted glycosylated laminin-\u03b12 is critical for local microenvironment.", "mechanism": "Loss of MuSC-secreted laminin-\u03b12 is not compensated by ECM-derived laminin-\u03b12, indicating a cell-autonomous requirement.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "Muscle regeneration impairment", "glycan_involvement": "Glycosylation required for functional protein in human cells.", "mechanism": "Human LAMA2-deficient myogenic precursors show downregulation of cell-cycle genes and impaired proliferation.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "LAMA2-related muscular dystrophy (LAMA2 MD, MDC1A)", "glycan_involvement": "Glycosylation defects may exacerbate protein instability.", "mechanism": "Laminin-\u03b12 deficiency leads to both muscle fiber frailty and intrinsic MuSC dysfunction.", "protein": "Laminin-\u03b12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12661008" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "NT-proBNP is a glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac wall stress and is associated with worse outcomes after M-TEER.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "high", "disease": "Mitral regurgitation", "glycan_involvement": "Glycosylation modulates NT-proBNP half-life and detection.", "mechanism": "High NT-proBNP (>5000 \u00b5g/L) predicts increased mortality after M-TEER.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Albumin glycosylation status can reflect inflammation and nutritional state.", "mechanism": "Low albumin is a marker of malnutrition and predicts poor survival after T-TEER.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Transferrin glycosylation patterns change in malnutrition and liver dysfunction.", "mechanism": "Altered transferrin levels indicate malnutrition, associated with increased mortality after TEER.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Cardiohepatic syndrome", "glycan_involvement": "Altered glycosylation in liver disease affects albumin function.", "mechanism": "Hypoalbuminemia reflects liver dysfunction and predicts poor outcome after TEER.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Pulmonary hypertension", "glycan_involvement": "Glycosylation influences NT-proBNP's plasma levels.", "mechanism": "NT-proBNP is elevated in pulmonary hypertension, indicating right ventricular strain.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation impacts NT-proBNP's immunoreactivity.", "mechanism": "NT-proBNP is increased in AF, reflecting atrial stretch and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "medium", "disease": "Cardiohepatic syndrome", "glycan_involvement": "Glycosylation changes in transferrin are markers of hepatic impairment.", "mechanism": "Transferrin alterations indicate liver dysfunction in cardiohepatic syndrome.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661571" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation (PMM2-CDG)", "glycan_involvement": "PMM2 is essential for the synthesis of GDP-mannose, a key substrate for N-glycosylation; its deficiency impairs glycoprotein biosynthesis.", "mechanism": "Reduced activity of PMM2 leads to defective glycosylation of proteins, resulting in multisystemic disease symptoms.", "protein": "Phosphomannomutase 2 (PMM2)", "protein_enriched": { "function": "E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 fa", "gene_name": "ATG7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95352" }, "relationship_type": "causal", "source_pmcid": "PMC12661638" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "MOG is a glycoprotein; its glycosylation may influence antigenicity and immune recognition.", "mechanism": "MOG acts as a key autoantigen targeted by autoreactive T and B cells, leading to demyelination and neurodegeneration.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12661838" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis", "glycan_involvement": "Glycosylation of MOG may affect disease induction and severity.", "mechanism": "Immunization with MOG peptide induces EAE, modeling MS pathology.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "causal", "source_pmcid": "PMC12661838" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation state of MOG may modulate immune tolerance efficacy.", "mechanism": "Antigen-specific tolerance induced by MOG-loaded PS liposomes ameliorates disease by expanding Treg and Breg cells.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12661838" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may affect MOG uptake and processing by phagocytes.", "mechanism": "MOG-loaded PS liposomes mimic apoptotic bodies, promoting tolerogenic antigen presentation and reducing inflammation.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "protective", "source_pmcid": "PMC12661838" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may influence antibody recognition of MOG.", "mechanism": "MOG-specific immune responses are used to monitor disease activity and therapeutic efficacy.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661838" }, { "confidence": "medium", "disease": "Aortic aneurysm", "glycan_involvement": "Altered glycosylation may affect structural integrity and immune recognition.", "mechanism": "Destruction of glycoprotein-rich extracellular matrix in the aortic wall contributes to aneurysm formation and rupture.", "protein": "Aortic valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12661918" }, { "confidence": "medium", "disease": "Beh\u00e7et\u2019s disease", "glycan_involvement": "IgG glycosylation modulates immune complex formation and inflammation.", "mechanism": "IgG4 staining used to rule out IgG4-related disease in vasculitic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12661918" }, { "confidence": "medium", "disease": "Beh\u00e7et\u2019s disease", "glycan_involvement": "TNFR glycosylation affects ligand binding and receptor stability.", "mechanism": "Anti-TNF therapy (infliximab) targets TNFR signaling to suppress vasculitic inflammation.", "protein": "Tumor necrosis factor receptor (TNFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12661918" }, { "confidence": "low", "disease": "Beh\u00e7et\u2019s disease", "glycan_involvement": "Glycosylation modulates IL-6R signaling and immune activation.", "mechanism": "IL-6R implicated in systemic inflammation and may be elevated in vasculitis.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "biomarker", "source_pmcid": "PMC12661918" }, { "confidence": "medium", "disease": "Aortic regurgitation", "glycan_involvement": "Altered glycosylation may increase susceptibility to immune-mediated damage.", "mechanism": "Inflammatory destruction of glycoprotein-rich valve tissue leads to regurgitation.", "protein": "Aortic valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12661918" }, { "confidence": "low", "disease": "Infective endocarditis", "glycan_involvement": "Glycosylation affects plasma cell migration and immune response.", "mechanism": "Plasma cell infiltration assessed to distinguish infection from vasculitis.", "protein": "Plasma cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12661918" }, { "confidence": "low", "disease": "Infective endocarditis", "glycan_involvement": "Pathogen recognition of glycan motifs on valve surface.", "mechanism": "Bacterial adhesion to valve glycoproteins initiates endocarditis.", "protein": "Aortic valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12661918" }, { "confidence": "medium", "disease": "Beh\u00e7et\u2019s disease", "glycan_involvement": "Glycan structures may modulate immune-mediated injury.", "mechanism": "Vasculitic destruction of glycoprotein-rich valve tissue contributes to cardiac complications.", "protein": "Aortic valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12661918" }, { "confidence": "low", "disease": "Infective endocarditis", "glycan_involvement": "Glycosylation affects antibody function and pathogen clearance.", "mechanism": "IgG used in serological testing for infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12661918" }, { "confidence": "low", "disease": "Aortic aneurysm", "glycan_involvement": "Receptor glycosylation modulates therapeutic efficacy.", "mechanism": "TNF-\u03b1 inhibition reduces inflammation and risk of aneurysm progression.", "protein": "Tumor necrosis factor receptor (TNFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12661918" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "CRP is a glycoprotein; its glycosylation affects stability and function as an inflammatory marker.", "mechanism": "CRP levels mediate ~32% of the protective effect of a gut-microbiota\u2013supportive diet on heart failure risk via inflammation reduction.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates CRP's circulatory half-life and immune interactions.", "mechanism": "Elevated CRP reflects systemic inflammation associated with increased diabetes risk; reduced by microbiota-supportive diet.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "CRP glycosylation influences its inflammatory activity.", "mechanism": "CRP mediates inflammation contributing to stroke risk; lower CRP linked to reduced stroke prevalence.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Kidney Failure", "glycan_involvement": "Glycosylation affects CRP's clearance and inflammatory signaling.", "mechanism": "CRP is elevated in kidney failure due to systemic inflammation; reduced by anti-inflammatory dietary components.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation state may influence CRP's role in chronic inflammation.", "mechanism": "High CRP predicts increased all-cause mortality; reduction mediates survival benefit of microbiota-supportive diet.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "high", "disease": "Cardiovascular Mortality", "glycan_involvement": "CRP glycosylation modulates its pro-inflammatory effects.", "mechanism": "CRP is a predictor of cardiovascular mortality; lower CRP mediates reduced risk with high DI-GM diet.", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Surface glycoproteins on neutrophils, platelets, and lymphocytes are involved in immune signaling.", "mechanism": "SII mediates ~26% of the protective effect of a gut-microbiota\u2013supportive diet on heart failure risk via immune cell balance.", "protein": "Systemic Immune-Inflammation Index (SII) components", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Immune cell glycoproteins modulate inflammatory responses.", "mechanism": "Elevated SII reflects immune dysregulation in diabetes; improved by anti-inflammatory diet.", "protein": "Systemic Immune-Inflammation Index (SII) components", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycoproteins on immune cells affect vascular inflammation.", "mechanism": "High SII is associated with increased stroke risk; reduced by microbiota-supportive diet.", "protein": "Systemic Immune-Inflammation Index (SII) components", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "medium", "disease": "Kidney Failure", "glycan_involvement": "Glycosylation of immune cell proteins influences inflammatory signaling.", "mechanism": "SII is elevated in kidney failure due to chronic inflammation; improved by dietary intervention.", "protein": "Systemic Immune-Inflammation Index (SII) components", "relationship_type": "biomarker", "source_pmcid": "PMC12661986" }, { "confidence": "high", "disease": "Cognitive impairment after ICH", "glycan_involvement": "FSTL1 is an extracellular glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "Serum FSTL1 levels at admission are inversely correlated with cognitive scores and independently predict 3-month cognitive impairment after ICH, likely via neuroinflammatory pathways.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12662422" }, { "confidence": "high", "disease": "Intracerebral hemorrhage (ICH)", "glycan_involvement": "Glycosylation required for extracellular stability and activity.", "mechanism": "Serum FSTL1 reflects neuroinflammatory response and severity of ICH.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation supports extracellular signaling and interaction with inflammatory mediators.", "mechanism": "FSTL1 upregulation exacerbates A\u03b21\u201342-induced neuronal damage and inflammation; also regulated by p300-mediated acetylation.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Neuropathic pain", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "FSTL1 modulates neuroinflammatory responses in neuropathic pain models.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation essential for extracellular activity.", "mechanism": "Circulating FSTL1 reflects severity and outcome of ischemic stroke via neuroinflammatory pathways.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12662422" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation supports stability and function.", "mechanism": "FSTL1 is involved in inflammatory and repair processes in cardiovascular disease.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12662422" }, { "confidence": "low", "disease": "Arthritis", "glycan_involvement": "Glycosylation required for immune modulation.", "mechanism": "FSTL1 participates in immune and inflammatory responses in arthritis.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Cognitive impairment after ICH", "glycan_involvement": "Glycosylation may affect receptor interactions and downstream signaling.", "mechanism": "Potential dual role: FSTL1 upregulation may worsen or protect cognitive function depending on context and signaling pathways.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12662422" }, { "confidence": "low", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation status may influence therapeutic efficacy.", "mechanism": "Targeting FSTL1 expression or function may modulate neuroinflammation and neuronal damage.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Cognitive impairment after ICH", "glycan_involvement": "Glycosylation necessary for FSTL1's extracellular signaling.", "mechanism": "FSTL1 may mediate neuroinflammation and neuronal injury, contributing to cognitive decline.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "causal", "source_pmcid": "PMC12662422" }, { "confidence": "medium", "disease": "Statin-induced myopathy", "glycan_involvement": "Glycosylation affects P-gp stability and function, modulating drug transport.", "mechanism": "Inhibition of P-glycoprotein increases statin exposure, raising myotoxicity risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12662601" }, { "confidence": "medium", "disease": "Statin-induced myopathy", "glycan_involvement": "N-glycosylation modulates OATP1B1 trafficking and function.", "mechanism": "OATP1B1 mediates hepatic statin uptake; inhibition increases systemic statin levels and muscle toxicity.", "protein": "OATP1B1 (SLCO1B1)", "protein_enriched": { "function": "Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taur", "gene_name": "SLCO1B1", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G34989PA", "G90659AW" ], "uniprot_id": "Q9Y6L6" }, "relationship_type": "causal", "source_pmcid": "PMC12662601" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "SGLT2 is N-glycosylated, affecting membrane localization and function.", "mechanism": "SGLT2 inhibitor-induced osmotic diuresis and volume depletion potentiate muscle injury.", "protein": "SGLT2 (SLC5A2)", "relationship_type": "causal", "source_pmcid": "PMC12662601" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Cardiac troponins are glycosylated, influencing clearance and detection.", "mechanism": "Troponin released from muscle during rhabdomyolysis, causing elevated serum levels.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12662601" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation is critical for PCSK9 secretion and LDLR binding.", "mechanism": "PCSK9 inhibitors lower LDL cholesterol, reducing cardiovascular risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12662601" }, { "confidence": "high", "disease": "Myoglobinuria", "glycan_involvement": "Myoglobin is not glycosylated; no direct glycan involvement.", "mechanism": "Myoglobin released from damaged muscle is filtered by kidneys, causing myoglobinuria.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12662601" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "NPC1L1 is N-glycosylated, affecting its trafficking and function.", "mechanism": "NPC1L1 inhibition reduces cholesterol absorption, lowering cardiovascular risk.", "protein": "Ezetimibe target (NPC1L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12662601" }, { "confidence": "medium", "disease": "Polypharmacy toxicity", "glycan_involvement": "Glycosylation modulates P-gp substrate specificity.", "mechanism": "Drug-drug interactions at P-gp increase risk of adverse effects.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12662601" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "N-glycosylation required for SGLT2 function.", "mechanism": "SGLT2 inhibitor-induced dehydration and hypovolemia contribute to AKI.", "protein": "SGLT2 (SLC5A2)", "relationship_type": "causal", "source_pmcid": "PMC12662601" }, { "confidence": "high", "disease": "Troponin elevation (non-ischemic)", "glycan_involvement": "Glycosylation may affect troponin clearance.", "mechanism": "Troponin elevation in rhabdomyolysis reflects muscle injury, not cardiac ischemia.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12662601" }, { "confidence": "high", "disease": "Epithelial Tumors", "glycan_involvement": "FAP is a glycoprotein; glycosylation is essential for its cell surface localization and function.", "mechanism": "FAP is overexpressed in >90% of epithelial tumors, enabling molecular imaging and diagnosis.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12663746" }, { "confidence": "high", "disease": "Epithelial Tumors", "glycan_involvement": "Glycosylation may affect FAP inhibitor binding and stability.", "mechanism": "FAP-targeted inhibitors (FAPI) enable image-guided therapy for epithelial cancers.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12663746" }, { "confidence": "high", "disease": "Neoplasms", "glycan_involvement": "Glycosylation supports FAP's cell surface expression and recognition by radiolabeled ligands.", "mechanism": "FAP is overexpressed in the majority of neoplasms, allowing for PET/CT imaging.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12663746" }, { "confidence": "high", "disease": "Neoplasms", "glycan_involvement": "Glycosylation may modulate FAP's interaction with inhibitors.", "mechanism": "Radiolabeled FAP inhibitors can be used for theranostic applications in cancer treatment.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12663746" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation affects AGP's anti-inflammatory properties and serum half-life.", "mechanism": "AGP is elevated in systemic inflammation, reflecting gut inflammatory status.", "protein": "alpha-1-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12664039" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation modulates CRP's immune recognition and clearance.", "mechanism": "CRP is an acute-phase reactant elevated during inflammation, including gut inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12664039" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "Bacterial glycoproteins interact with host mucins and immune receptors.", "mechanism": "Bifidobacterium abundance is associated with reduced risk of diarrhea; surface glycoproteins mediate colonization and immune modulation.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12664039" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "Surface glycoproteins facilitate host-microbe interactions.", "mechanism": "Lactobacillus abundance is linked to lower diarrhea risk; glycoproteins aid in mucosal adherence and pathogen exclusion.", "protein": "Lactobacillus surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12664039" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "Outer membrane glycoproteins are involved in host invasion and immune evasion.", "mechanism": "Increased Enterobacteriaceae (including pathogenic E. coli) is associated with higher diarrhea incidence.", "protein": "Enterobacteriaceae outer membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12664039" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "Glycoproteins mediate adhesion and immune modulation.", "mechanism": "Pathogenic Escherichia-Shigella strains cause diarrhea via toxin production and mucosal invasion.", "protein": "Escherichia-Shigella outer membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12664039" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "Glycosylation affects AGP's function as an inflammation marker.", "mechanism": "AGP is used to adjust ferritin values for inflammation in iron status assessment.", "protein": "alpha-1-acid glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC12664039" }, { "confidence": "medium", "disease": "Poor growth (stunting)", "glycan_involvement": "Glycoproteins mediate nutrient utilization and immune signaling.", "mechanism": "Higher Bifidobacterium abundance is associated with better growth outcomes.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12664039" }, { "confidence": "medium", "disease": "Environmental enteric dysfunction", "glycan_involvement": "Glycoproteins facilitate epithelial interaction and immune activation.", "mechanism": "Overgrowth of Enterobacteriaceae is linked to enteric dysfunction and inflammation.", "protein": "Enterobacteriaceae outer membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12664039" }, { "confidence": "medium", "disease": "Poor growth (stunting)", "glycan_involvement": "CRP glycosylation influences its inflammatory signaling.", "mechanism": "Elevated CRP reflects systemic inflammation, which is associated with growth impairment.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12664039" }, { "confidence": "high", "disease": "Subclinical interstitial lung disease", "glycan_involvement": "B2GP1 is a glycoprotein; glycosylation may affect its immunogenicity and endothelial interactions.", "mechanism": "Higher serum B2GP1 antibody levels (IgA, IgG, IgM) are associated with increased high attenuation areas (HAA) on CT, indicating lung injury/inflammation.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Glycosylation of B2GP1 may modulate antibody binding and pathogenicity.", "mechanism": "Elevated B2GP1 antibodies found in patients with ILD, suggesting a role in endothelial injury and fibrogenesis.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "high", "disease": "Subclinical interstitial lung disease", "glycan_involvement": "Glycosylation may influence B2GP1's interaction with endothelial receptors (e.g., annexin II).", "mechanism": "Association between B2GP1 antibody levels and HAA is strongest in moderate smokers (10\u201320 pack years), suggesting interaction with smoking-induced endothelial dysfunction.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "B2GP1 is a major antigen in APS, driving autoantibody production and prothrombotic state.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12664236" }, { "confidence": "high", "disease": "Subclinical interstitial lung disease", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation may affect antigen-antibody interactions.", "mechanism": "Higher aCL antibody levels (IgA, IgG, IgM) are associated with increased HAA in White individuals, indicating early lung injury.", "protein": "Anticardiolipin antibody (aCL)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Indirect; aCL targets glycoproteins involved in endothelial function.", "mechanism": "Elevated aCL antibodies detected in ILD patients, possibly contributing to endothelial injury.", "protein": "Anticardiolipin antibody (aCL)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycosylated proteins; glycosylation may affect immune response.", "mechanism": "aCL is a diagnostic marker and pathogenic antibody in APS.", "protein": "Anticardiolipin antibody (aCL)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12664236" }, { "confidence": "medium", "disease": "Subclinical interstitial lung disease", "glycan_involvement": "Glycosylation may influence B2GP1's immunogenicity in different populations.", "mechanism": "B2GP1 antibody-HAA association is stronger in Hispanic individuals, suggesting population-specific risk.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "low", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation may modulate B2GP1's pathogenic effects.", "mechanism": "B2GP1 antibodies may contribute to capillary endothelial injury and fibrogenesis.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "causal (suggested)", "source_pmcid": "PMC12664236" }, { "confidence": "medium", "disease": "Endothelial dysfunction (precursor to ILD)", "glycan_involvement": "Glycosylation affects B2GP1's interaction with endothelial receptors.", "mechanism": "B2GP1 antibodies accelerate endothelial cell apoptosis, promoting vascular remodeling.", "protein": "Beta-2 glycoprotein 1 (B2GP1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12664236" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and trafficking.", "mechanism": "AEP cleaves APP at N373 and N585, generating neurotoxic and amyloidogenic fragments that increase A\u03b2 production.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12664493" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; glycosylation modulates aggregation and phosphorylation.", "mechanism": "AEP cleaves Tau at N255 and N368, producing aggregation-prone, neurotoxic fragments that promote NFT formation.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "LF is glycosylated; glycosylation is essential for receptor binding and nanoparticle stability.", "mechanism": "LF stabilizes zein nanoparticles and enhances brain delivery of AEP inhibitor via transferrin receptor-mediated uptake.", "protein": "Lactoferrin (LF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Cystatin C is glycosylated; glycosylation may affect stability and inhibitory function.", "mechanism": "Cystatin C inhibits AEP and binds soluble A\u03b2, preventing oligomerization and exerting neuroprotective effects.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12664493" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is glycosylated; glycosylation influences its trafficking and activity.", "mechanism": "AEP cleaves BACE1 at N294, increasing its activity and A\u03b2 production.", "protein": "BACE1 (Beta-secretase 1)", "protein_enriched": { "function": "Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generatio", "gene_name": "BACE1", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G80920RR", "G05724UK", "G06110VR", "G12398HZ", "G14023ZV", "G14669DU", "G15065YV", "G17689DH", "G21112KH", "G22310AV", "G22768VO", "G23863VK", "G25520XG", "G29880MM", "G39188ZX", "G44444MB", "G46687AB", "G49874UX", "G55220VL", "G60230HH", "G63889NK", "G64527OM", "G70101JE", "G70375MX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G80966KZ", "G84452RH", "G87618BG", "G90093AU", "G91636VS", "G93993PD", "G94854LT" ], "uniprot_id": "P56817" }, "relationship_type": "causal", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "SET is glycosylated; glycosylation may affect nuclear localization and function.", "mechanism": "AEP cleaves SET at N175, triggering neuronal cell death.", "protein": "SET nuclear protein", "protein_enriched": { "function": "Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14699129, PubMed:14738735). Required for", "gene_name": "SPC25", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HBM1" }, "relationship_type": "causal", "source_pmcid": "PMC12664493" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AEP is glycosylated; glycosylation regulates its lysosomal localization and activity.", "mechanism": "AEP is upregulated and activated in AD, cleaving APP, Tau, and BACE1, driving pathology; inhibition ameliorates disease.", "protein": "Asparagine endopeptidase (AEP, Legumain)", "protein_enriched": { "function": "Has a strict specificity for hydrolysis of asparaginyl bonds (PubMed:23776206). Can also cleave aspartyl bonds slowly, especially under acidic conditions (PubMed:23776206). Involved in the processing ", "gene_name": "LGMN", "glycan_count": 31, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G70994MS", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10486CT", "G14669DU", "G25079LO", "G28681TP", "G31852PQ", "G39188ZX", "G41247ZX", "G43769HG", "G62765YT", "G80920RR", "G80966KZ", "G83460ZZ", "G90659AW", "G92050GC", "G00912UN", "G26436YP", "G26915XM", "G29545VG", "G36442WJ", "G54010QB", "G94470IW", "G57292HF", "G17015OC", "G03238UC" ], "uniprot_id": "Q99538" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Tau glycosylation modulates immune signaling.", "mechanism": "AEP-generated Tau fragments activate STAT1, upregulating BACE1 and exacerbating neuroinflammation.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation status affects biomarker detection.", "mechanism": "APP cleavage fragments serve as biomarkers for AD and dementia progression.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC12664493" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Receptor glycosylation is critical for ligand binding and endocytosis.", "mechanism": "Transferrin receptor mediates uptake of LF-stabilized nanoparticles, enhancing CNS drug delivery.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12664493" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and immune complex formation.", "mechanism": "Autoantigen for aPL; binding triggers immune response and thrombosis.", "protein": "\u03b22-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC12664860" }, { "confidence": "high", "disease": "Atherosclerotic vascular disease (ASVD)", "glycan_involvement": "Glycosylation modulates \u03b22GPI-lipoprotein interactions.", "mechanism": "Forms complexes with oxLDL, promotes foam cell formation and plaque development.", "protein": "\u03b22-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC12664860" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Fc glycosylation may affect effector function and immune complex clearance.", "mechanism": "IgG aPL (aCL, a\u03b22GPI) associated with increased MI risk via thrombosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12664860" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects IgM structure and immune activation.", "mechanism": "IgM aPL detected in APS patients with MI, but evidence is inconsistent.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12664860" }, { "confidence": "high", "disease": "Atherosclerotic vascular disease (ASVD)", "glycan_involvement": "Glycosylation required for complement assembly/function.", "mechanism": "Complement activation promotes inflammation, plaque instability, and thrombosis.", "protein": "Complement C5-C9", "relationship_type": "causal", "source_pmcid": "PMC12664860" }, { "confidence": "high", "disease": "Atherosclerotic vascular disease (ASVD)", "glycan_involvement": "N-glycosylation essential for VCAM-1 function.", "mechanism": "Upregulated by aPL, promotes leukocyte adhesion and vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12664860" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation modulates TF activity.", "mechanism": "Induced by aPL, triggers coagulation cascade and thrombosis.", "protein": "Tissue factor", "relationship_type": "causal", "source_pmcid": "PMC12664860" }, { "confidence": "medium", "disease": "Atherosclerotic vascular disease (ASVD)", "glycan_involvement": "Glycosylation affects LDL structure and immune recognition.", "mechanism": "Component of LDL; forms complexes with \u03b22GPI, promoting foam cell formation.", "protein": "Apolipoprotein B-100", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12664860" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation influences matrix interactions.", "mechanism": "Enriched in APS plasma clots; may contribute to prothrombotic state.", "protein": "Thrombospondin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12664860" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Decreased in APS clots; normally inhibits coagulation and inflammation.", "protein": "Histidine-rich glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12664860" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Dystrophin anchors glycosylated DGC members; loss disrupts glycoprotein complex.", "mechanism": "Loss-of-function mutations in dystrophin gene cause absence of dystrophin, leading to destabilization of muscle membrane and DGC.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12664987" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b2-Dystroglycan is heavily glycosylated; glycosylation is critical for DGC assembly.", "mechanism": "Loss of dystrophin impairs \u03b2-dystroglycan membrane localization and stability.", "protein": "\u03b2-Dystroglycan", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12664987" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03b1-Dystroglycan O-mannosyl glycosylation is essential for ECM interaction.", "mechanism": "Dystrophin loss disrupts \u03b1-dystroglycan function in ECM binding.", "protein": "\u03b1-Dystroglycan", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Utrophin interacts with glycosylated DGC members.", "mechanism": "Upregulation of utrophin can partially compensate for dystrophin loss.", "protein": "Utrophin", "protein_enriched": { "function": "May play a role in anchoring the cytoskeleton to the plasma membrane", "gene_name": "UTRN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "P46939" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12664987" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "\u03bcDys enables partial reassembly of glycoprotein complex.", "mechanism": "Gene therapy delivers truncated \u03bcDys to restore partial DGC function.", "protein": "Micro-dystrophin (\u03bcDys)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Fibronectin is glycosylated; glycosylation affects ECM deposition.", "mechanism": "Elevated TGF-\u03b2 in DMD stimulates fibronectin production, contributing to fibrosis.", "protein": "Fibronectin (FN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Collagen glycosylation modulates ECM structure.", "mechanism": "TGF-\u03b2-driven collagen accumulation leads to muscle fibrosis.", "protein": "Collagens", "relationship_type": "biomarker", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Caveolin-3 is glycosylated; glycosylation may affect membrane localization.", "mechanism": "Dystrophin loss alters caveolin-3/\u03b2-dystroglycan interaction, affecting calcium channel activity.", "protein": "Caveolin-3", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium cha", "gene_name": "CAV3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56539" }, "relationship_type": "causal/modulatory", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "TfR1 glycosylation affects receptor-mediated endocytosis.", "mechanism": "TfR1-targeted antibody conjugates improve delivery of ASOs to muscle cells.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12664987" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of \u03b2-dystroglycan is essential for cardiac DGC stability.", "mechanism": "Disrupted \u03b2-dystroglycan function in heart muscle contributes to cardiac complications in DMD.", "protein": "\u03b2-Dystroglycan", "relationship_type": "causal", "source_pmcid": "PMC12664987" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for APS and mediate thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "ischemic stroke", "glycan_involvement": "Glycosylation modulates immune recognition and thrombogenicity.", "mechanism": "APS patients with anti-beta-2 glycoprotein I antibodies have increased risk of arterial thrombosis, including stroke.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "deep vein thrombosis (DVT)", "glycan_involvement": "Glycosylation influences antibody binding and prothrombotic activity.", "mechanism": "APS increases risk of venous thrombosis via anti-beta-2 glycoprotein I antibodies.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Antibody glycosylation affects effector function and pathogenicity.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "ischemic stroke", "glycan_involvement": "Fc glycosylation modulates inflammatory and thrombotic potential.", "mechanism": "APS patients with anticardiolipin antibodies are at increased risk for arterial thrombosis and stroke.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "deep vein thrombosis (DVT)", "glycan_involvement": "Antibody glycosylation influences complement activation and thrombosis.", "mechanism": "APS increases risk of venous thrombosis via anticardiolipin antibodies.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "medium", "disease": "paradoxical embolism", "glycan_involvement": "Glycosylation affects thrombogenicity and immune complex formation.", "mechanism": "APS-mediated thrombosis can lead to venous thrombi crossing PFO, causing paradoxical embolism.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "medium", "disease": "paradoxical embolism", "glycan_involvement": "Antibody glycosylation modulates pathogenicity.", "mechanism": "APS-related antibodies promote thrombosis, increasing risk of emboli crossing PFO.", "protein": "anticardiolipin antibody (IgG/IgM)", "relationship_type": "causal", "source_pmcid": "PMC12665290" }, { "confidence": "high", "disease": "Thoracic aortic aneurysm and dissection (TAAD)", "glycan_involvement": "Increases UDP-GlcNAc for N- and O-glycosylation, fueling ECM glycoprotein and GAG synthesis.", "mechanism": "Upregulation drives excessive glycosylation, leading to glycan-rich matrix accumulation and medial degeneration.", "protein": "GFPT2 (glutamine-fructose-6-phosphate transaminase 2)", "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "high", "disease": "TAAD", "glycan_involvement": "O-glycosylation of cytoplasmic/nuclear proteins increases.", "mechanism": "Elevated O-GlcNAc levels in aortic tissue indicate HBP activation and disease state.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12665370" }, { "confidence": "medium", "disease": "TAAD", "glycan_involvement": "N-glycosylation of secreted and ECM proteins.", "mechanism": "Upregulation enhances N-glycosylation of ECM proteins, contributing to matrix accumulation.", "protein": "MGATs (Mgat1, Mgat2, Mgat4a, Mgat5b)", "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "high", "disease": "Aortic medial degeneration", "glycan_involvement": "Glycosaminoglycan side chains increase negative charge and water retention.", "mechanism": "Accumulation disrupts ECM structure, increases osmotic pressure, and promotes medial thickening.", "protein": "Proteoglycans (Acan, Vcan, Sdc4)", "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "medium", "disease": "TAAD", "glycan_involvement": "Synthesis of hyaluronic acid (GAG).", "mechanism": "Increased expression leads to excess hyaluronic acid, contributing to ECM swelling.", "protein": "Hyaluronan synthases (HAS1, HAS3)", "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "medium", "disease": "TAAD", "glycan_involvement": "O-glycosylation of intracellular proteins.", "mechanism": "Upregulation increases O-GlcNAcylation, affecting VSMC function and stress response.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "high", "disease": "TAAD", "glycan_involvement": "Triggered by excessive glycosylation and ER stress.", "mechanism": "ISR activation via HBP increases ATF4 translation, leading to maladaptive stress signaling.", "protein": "ATF4", "protein_enriched": { "function": "Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cel", "gene_name": "ATF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P18848" }, "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "high", "disease": "Marfan syndrome (MFS)", "glycan_involvement": "Increased GAG synthesis and release.", "mechanism": "Elevated circulating GAGs reflect ECM remodeling and disease activity.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "biomarker", "source_pmcid": "PMC12665370" }, { "confidence": "medium", "disease": "TAAD", "glycan_involvement": "N- and O-glycosylation modulate secretion and function.", "mechanism": "Reduced by HBP inhibition, suggesting involvement in ECM pathology.", "protein": "Thrombospondin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12665370" }, { "confidence": "medium", "disease": "Vascular ageing", "glycan_involvement": "O-glycosylation of cellular proteins increases with age.", "mechanism": "Increased O-GlcNAcylation in aged vessels contributes to ECM changes and degeneration.", "protein": "O-GlcNAc-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12665370" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation may affect its detection and function.", "mechanism": "Elevated serum AFP is associated with HCC development and progression.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "HBeAg is glycosylated, which affects its immunogenicity and stability.", "mechanism": "Presence of HBeAg indicates active viral replication and higher risk of disease progression.", "protein": "Hepatitis B e Antigen (HBeAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Platelet surface glycoproteins mediate platelet function and clearance.", "mechanism": "Low platelet count is a risk factor for HCC, reflecting underlying liver fibrosis/cirrhosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin glycosylation status may change in liver disease.", "mechanism": "Reduced serum albumin indicates impaired liver synthetic function in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "Elevated GGT is associated with HCC and poor tumor differentiation.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "AST is glycosylated; glycan changes may occur in liver disease.", "mechanism": "Elevated AST reflects hepatocyte injury in chronic hepatitis B.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "ALP glycosylation affects its stability and activity.", "mechanism": "Elevated ALP is associated with HCC and advanced liver disease.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation pattern of AFP can distinguish HCC from cirrhosis.", "mechanism": "AFP may be elevated in cirrhosis, but higher levels are more specific for HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of HBeAg modulates immune response and viral persistence.", "mechanism": "Active HBV replication (HBeAg+) increases risk of HCC development.", "protein": "Hepatitis B e Antigen (HBeAg)", "relationship_type": "causal", "source_pmcid": "PMC12683684" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation may affect platelet lifespan.", "mechanism": "Thrombocytopenia due to splenic sequestration and reduced thrombopoietin in cirrhosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12683684" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Albumin glycosylation may affect stability and half-life; hypoalbuminemia can reflect altered glycosylation in disease.", "mechanism": "Low serum albumin predicts increased mortality in COVID-19, reflecting hepatic dysfunction, malnutrition, or systemic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "AST is glycosylated; altered glycosylation may affect enzyme activity and release during tissue injury.", "mechanism": "Elevated AST is associated with increased mortality and may indicate hepatic and extrahepatic (mitochondrial/muscle) injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ALT glycosylation may modulate enzyme stability and release during liver injury.", "mechanism": "ALT elevation independently predicts mortality, reflecting hepatocyte injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects enzyme activity and clearance.", "mechanism": "Elevated alkaline phosphatase is associated with worse outcomes, indicating cholestatic or hepatic injury.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding and cell surface expression.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2 in GI and hepatic cells, mediating direct viral injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects TMPRSS2 localization and protease activity.", "mechanism": "TMPRSS2 primes SARS-CoV-2 spike protein for cell entry in GI and hepatic tissues.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation influences its clearance and detection.", "mechanism": "Elevated D-dimer predicts increased mortality, reflecting coagulopathy and systemic inflammation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields spike from immune recognition and modulates infectivity.", "mechanism": "Spike protein mediates viral entry via ACE2/TMPRSS2 in GI and hepatic cells, causing direct injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "Altered glycosylation may occur in malnutrition, affecting albumin function.", "mechanism": "Low albumin reflects malnutrition, which increases risk of poor COVID-19 outcomes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683944" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation affects antibody-dependent cellular cytotoxicity and anti-inflammatory properties.", "mechanism": "IgG response is critical for viral clearance; glycosylation modulates effector function and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12683944" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Heavily N-glycosylated; glycans shield E2 from neutralizing antibodies.", "mechanism": "E2 mediates viral entry into hepatocytes and immune evasion.", "protein": "Hepatitis C Virus Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates immune recognition and chronicity.", "mechanism": "Chronic infection via E2 leads to persistent inflammation and fibrosis.", "protein": "Hepatitis C Virus Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects stability and serum levels.", "mechanism": "Elevated GGT indicates hepatocyte injury and fibrosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion.", "mechanism": "ALT elevation reflects hepatocellular injury in HCV.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "AST is glycosylated; glycosylation may affect serum half-life.", "mechanism": "AST elevation correlates with liver inflammation and fibrosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "ALP glycosylation modulates enzyme activity and clearance.", "mechanism": "ALP elevation is associated with cholestasis and advanced fibrosis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683945" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Albumin glycosylation status may change in liver disease.", "mechanism": "Decreased albumin reflects impaired liver synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683945" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation shields E2, supporting persistent infection and carcinogenesis.", "mechanism": "Chronic HCV infection via E2 promotes oncogenic transformation.", "protein": "Hepatitis C Virus Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC12683945" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and receptor binding.", "mechanism": "Elevated IL-6 correlates with advanced HCC stage, reflecting inflammation and tumor progression via JAK/STAT3 pathway.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "IL-10 glycosylation modulates secretion and activity.", "mechanism": "Higher IL-10 in early HCC (BCLC A) suggests anti-inflammatory response and tumor-induced immunosuppression.", "protein": "Interleukin-10", "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation affects IL-6 serum half-life.", "mechanism": "IL-6 levels are elevated in cirrhosis, indicating chronic inflammation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation influences IL-10 anti-inflammatory function.", "mechanism": "IL-10 modulates inflammation and fibrosis in cirrhosis.", "protein": "Interleukin-10", "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 secretion.", "mechanism": "TNF-\u03b1 promotes inflammation, apoptosis, and necrosis in HCC.", "protein": "Tumor Necrosis Factor Alpha", "relationship_type": "causal", "source_pmcid": "PMC12683946" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Albumin glycosylation altered in liver disease, affecting function.", "mechanism": "Reduced albumin reflects impaired liver synthetic function and poor prognosis in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation status may affect stability and transport function.", "mechanism": "Lower prealbumin indicates advanced liver injury and poor nutritional status.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect enzyme activity and release.", "mechanism": "Elevated AST reflects hepatocyte necrosis and tumor burden.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may modulate enzyme stability.", "mechanism": "Elevated ALT indicates liver cell damage in HCC.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12683946" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects IL-10 receptor interaction.", "mechanism": "Targeting IL-10 may limit tumor-induced immunosuppression in early HCC.", "protein": "Interleukin-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12683946" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation modulates APOE structure and function, impacting lipid binding and clearance.", "mechanism": "APOE \u03b54 allele increases AD risk via effects on cholesterol metabolism, neuroinflammation, and amyloid deposition.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "GlycA reflects N-acetyl glycan modifications on acute-phase glycoproteins.", "mechanism": "Elevated GlycA levels indicate systemic inflammation, associated with poorer cognitive performance and AD.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosphingolipid structure influences membrane signaling and neurodegeneration.", "mechanism": "Elevated sphingomyelin in brain and CSF of AD patients; conversion to ceramides promotes neuronal aging and death.", "protein": "Sphingomyelin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12689267" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "LDL contains glycoproteins whose glycosylation affects receptor binding and clearance.", "mechanism": "LDL particle diameter and cholesterol content are predictive for AD; altered lipid metabolism linked to cognitive decline.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "HDL-associated glycoproteins' glycosylation modulates anti-inflammatory properties.", "mechanism": "HDL cholesteryl esters distinguish MCI from AD and HC; HDL function is neuroprotective.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "low", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycoproteins involved in BCAA transport/metabolism may be glycosylated, affecting function.", "mechanism": "Altered BCAA levels are predictive for AD; mechanism unclear but may reflect metabolic dysregulation.", "protein": "Branched-chain amino acids (BCAA)-related glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "low", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation affects CETP stability and activity.", "mechanism": "Altered cholesterol ester transfer may contribute to AD risk via lipid imbalance.", "protein": "Cholesteryl ester transfer protein (CETP)", "protein_enriched": { "function": "Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL t", "gene_name": "CETP", "glycan_count": 15, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G27058EU", "G45395BF", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G90659AW", "G43417UB", "G00912UN", "G10486CT", "G14796IU", "G59626AS", "G86795LJ" ], "uniprot_id": "P11597" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "low", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation modulates PLTP function.", "mechanism": "Altered phospholipid transfer in lipoprotein particles is associated with AD.", "protein": "Phospholipid transfer protein (PLTP)", "protein_enriched": { "function": "Mediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoprotei", "gene_name": "PLTP", "glycan_count": 78, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G23505EP", "G99966GV", "G02815KT", "G10486CT", "G11314AS", "G27058EU", "G31852PQ", "G35541EV", "G38663NM", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G45495MK", "G57776ZS", "G62765YT", "G70441OD", "G70619PT", "G79666IR", "G80920RR", "G83460ZZ", "G84452RH", "G87661QW", "G90659AW", "G93718GY", "G04657PL", "G20312EM", "G22310AV", "G43089EG", "G43223CG", "G56784JY", "G88374WZ", "G49108TO", "G08290VR", "G08293MJ", "G10339FR", "G10488MI", "G20706XG", "G29880MM", "G51413EV", "G77669RF", "G78787DI", "G57321FI", "G00912UN", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11629QQ", "G14796IU", "G23719VF", "G27947YN", "G37881RL", "G40926MX", "G43669FQ", "G44753VC", "G47644PP", "G49906RN", "G49955PK", "G51640FO", "G57776ZU", "G59324HL", "G59626AS", "G59924QI", "G60033FS", "G63041LO", "G65184UU", "G69521XL", "G70232NH", "G72790NZ", "G80075MS", "G81263BG", "G85144OK", "G85269DF", "G86752LQ", "G95177YH", "G95865ZB" ], "uniprot_id": "P55058" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N- and O-glycosylation of APP affects cleavage and aggregation.", "mechanism": "APP processing generates amyloid beta, a hallmark of AD pathology.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689267" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "O-glycosylation modulates tau aggregation and toxicity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles in AD.", "protein": "Tau protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12689267" }, { "confidence": "high", "disease": "Fecal incontinence (FI)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Low serum albumin (component of GNRI) is associated with increased FI risk, reflecting poor nutritional status and muscle atrophy.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Fecal incontinence (FI)", "glycan_involvement": "CRP is N-glycosylated; glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP reflects systemic inflammation, which mediates increased FI risk in stroke.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Fecal incontinence (FI)", "glycan_involvement": "IL-6 is N-glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "High IL-6 impairs enteric neuron function and promotes muscle catabolism, increasing FI risk.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Fecal incontinence (FI)", "glycan_involvement": "IL-12 is N-glycosylated; glycosylation is required for secretion.", "mechanism": "Elevated IL-12 indicates chronic inflammation, contributing to neuromuscular dysfunction in FI.", "protein": "Interleukin-12 (IL-12)", "protein_enriched": { "function": "Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine (PubMed:8605935, PubMed:8943050). IL-12 is primarily produced by professional antigen-presenting cel", "gene_name": "IL12A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P29459" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects clotting function.", "mechanism": "High fibrinogen correlates with increased SII and stroke risk via pro-thrombotic and inflammatory pathways.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "low", "disease": "Fecal incontinence (FI)", "glycan_involvement": "REG3G is a secreted glycoprotein; glycosylation is important for secretion and function.", "mechanism": "REG3G supports intestinal barrier function; impaired expression (e.g., by smoking) increases FI risk.", "protein": "REG3G", "relationship_type": "protective", "source_pmcid": "PMC12689289" }, { "confidence": "low", "disease": "Fecal incontinence (FI)", "glycan_involvement": "TSG6 is N-glycosylated; glycosylation affects extracellular matrix interactions.", "mechanism": "TSG6 is involved in intestinal muscle repair; dysregulation (e.g., by smoking) impairs repair, increasing FI risk.", "protein": "TSG6", "relationship_type": "protective", "source_pmcid": "PMC12689289" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "N-glycosylation affects albumin stability and function.", "mechanism": "Low serum albumin (low GNRI) predicts poor stroke outcomes due to malnutrition and impaired repair.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation modulates CRP\u2019s inflammatory properties.", "mechanism": "High CRP is associated with increased stroke risk and severity via systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "N-glycosylation affects albumin\u2019s circulatory half-life.", "mechanism": "Low albumin reflects malnutrition, a risk factor for sarcopenia, which contributes to FI.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12689289" }, { "confidence": "high", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect its surface expression and antibody recognition.", "mechanism": "Aberrant expression of CD20 on T-cells serves as a diagnostic pitfall and may indicate a more aggressive disease course.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation of CD20 may influence antibody binding and efficacy.", "mechanism": "CD20 expression enables the use of anti-CD20 monoclonal antibodies (e.g., rituximab) as a therapeutic option.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689291" }, { "confidence": "high", "disease": "B-cell non-Hodgkin lymphoma (B-NHL)", "glycan_involvement": "Glycosylation is required for proper folding and surface expression.", "mechanism": "CD20 is a standard diagnostic marker for B-cell lineage in lymphomas.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "high", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "CD3 is a glycoprotein; glycosylation is important for TCR complex assembly.", "mechanism": "CD3 positivity confirms T-cell lineage in PTCL-NOS.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation modulates cell adhesion properties.", "mechanism": "CD2 expression supports T-cell origin.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation affects surface expression.", "mechanism": "CD5 is variably expressed in PTCL-NOS; its absence may be a histopathological feature.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Heavily O-glycosylated; sialylation modulates cell-cell interactions.", "mechanism": "CD43 positivity supports T-cell lineage.", "protein": "CD43", "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation may affect CD20 stability and immune recognition.", "mechanism": "Aberrant CD20 expression is associated with more aggressive disease and poor prognosis.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC12689291" }, { "confidence": "medium", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation of CD20 and Fc region of antibody influences ADCC and CDC.", "mechanism": "Rituximab (anti-CD20) may improve outcomes in CD20+ PTCL-NOS, but efficacy is variable.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689291" }, { "confidence": "low", "disease": "Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)", "glycan_involvement": "Glycosylation required for BCR complex assembly.", "mechanism": "Scattered CD79\u03b1 positivity may confound diagnosis; not typical for PTCL-NOS.", "protein": "CD79\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12689291" }, { "confidence": "high", "disease": "Breast carcinoma (HER2-positive)", "glycan_involvement": "HER2 is a glycoprotein; its N-glycosylation is essential for proper folding, stability, and receptor function.", "mechanism": "HER2 overexpression drives tumor proliferation and is targeted by trastuzumab and other anti-HER2 therapies.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689299" }, { "confidence": "high", "disease": "Breast carcinoma (HER2-positive)", "glycan_involvement": "Glycosylation affects HER2 detection and antibody binding.", "mechanism": "HER2 status is used to classify breast cancer subtype and guide therapy.", "protein": "HER2", "relationship_type": "biomarker", "source_pmcid": "PMC12689299" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "Albumin is N-glycosylated; altered glycosylation may affect serum levels and function.", "mechanism": "Lower serum albumin is used in the NAFLD Fibrosis Score to indicate advanced fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689368" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Non-enzymatic glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "Elevated HbA1c is a marker of impaired glucose metabolism, a criterion for MASLD.", "protein": "Glycosylated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins are essential for function; altered glycosylation may affect clearance.", "mechanism": "Platelet count is used in NFS and FIB-4 scores; thrombocytopenia is associated with fibrosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12689368" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "TGF-\u03b21 is N-glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "TGF-\u03b21/Smad pathway promotes hepatic stellate cell activation and fibrosis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "TIMP-1 is N-glycosylated; glycosylation modulates stability and activity.", "mechanism": "TIMP-1 inhibits matrix metalloproteinases, promoting extracellular matrix accumulation in fibrosis.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "causal", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 promotes inflammation and hepatic stellate cell activation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "PPAR-\u03b3 glycosylation status may affect nuclear localization and function.", "mechanism": "Activation of PPAR-\u03b3 inhibits TGF-\u03b21/Smad signaling, reducing fibrosis.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "\u03b1SMA can be O-glycosylated; glycosylation may affect filament assembly.", "mechanism": "\u03b1SMA expression marks activated hepatic stellate cells in fibrosis.", "protein": "\u03b1SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "GLP-1 is O-glycosylated; glycosylation affects stability and receptor binding.", "mechanism": "GLP-1 enhances insulin secretion; capsaicin increases GLP-1, improving glucose homeostasis.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689368" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL-associated glycoproteins are N- and O-glycosylated; glycosylation modulates lipid transport.", "mechanism": "Low HDL is a criterion for MASLD; HDL function depends on glycoprotein composition.", "protein": "HDL-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12689368" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "APS glycan structure mimics PAMPs, facilitating TLR4 engagement.", "mechanism": "APS binds TLR4, activates MyD88/NF-\u03baB pathway, enhances anti-tumor immunity.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "APS acts as a molecular mimic, stimulating humoral response.", "mechanism": "APS induces endogenous anti-PD-1 antibodies, blocking PD-1/PD-L1 interaction, reversing T cell exhaustion.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Indirect modulation via immune cell signaling.", "mechanism": "APS downregulates PD-L1 expression in tumor microenvironment, relieving immunosuppression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "APS mannose-rich glycan interacts with MR.", "mechanism": "APS upregulates MR expression, potentially enhancing anti-inflammatory responses.", "protein": "Mannose Receptor (MR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "APS \u03b2-glucan-like structures engage Dectin-1.", "mechanism": "APS may synergistically activate Dectin-1 and TLR4, amplifying anti-tumor immune response.", "protein": "Dectin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "APS antioxidant properties modulate NLRP3 activation.", "mechanism": "APS inhibits NLRP3 inflammasome activation, reducing IL-1\u03b2/IL-18 and inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Fibrosis (Hepatic)", "glycan_involvement": "APS modulates cytokine signaling, not direct glycan interaction.", "mechanism": "APS inhibits TGF-\u03b21/Smad2/3 signaling, reducing myofibroblast activation and ECM deposition.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Indirect; APS modulates signaling cascades.", "mechanism": "APS suppresses EGFR pathway, inhibiting tumor proliferation and metastasis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Indirect; APS influences apoptotic signaling.", "mechanism": "APS alters Bcl-2/Bax ratio, promoting apoptosis in tumor cells.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689378" }, { "confidence": "low", "disease": "Neurodegenerative Disorders", "glycan_involvement": "Indirect; APS modulates neuroprotective signaling.", "mechanism": "APS upregulates CREB phosphorylation, improving neuronal survival and cognitive function.", "protein": "CREB", "protein_enriched": { "function": "Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity", "gene_name": "CREB1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G70994MS" ], "uniprot_id": "P16220" }, "relationship_type": "protective", "source_pmcid": "PMC12689378" }, { "confidence": "high", "disease": "Cognitive impairment (CI)", "glycan_involvement": "Insulin is a glycoprotein; altered glycosylation may affect its stability and receptor interaction.", "mechanism": "Impaired insulin signaling in the brain leads to neuronal dysfunction and degeneration, contributing to CI.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "medium", "disease": "Cognitive impairment (CI)", "glycan_involvement": "N-glycosylation of the receptor is critical for function; altered glycosylation may reduce signaling.", "mechanism": "Reduced insulin receptor signaling in cognition-related brain regions impairs synaptic plasticity and memory.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "medium", "disease": "Cognitive impairment (CI)", "glycan_involvement": "APP is N- and O-glycosylated; aberrant glycosylation can affect amyloidogenic processing.", "mechanism": "Diabetes-induced oxidative stress and glycation promote amyloid deposition, contributing to CI.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "low", "disease": "Cognitive impairment (CI)", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its stability and function.", "mechanism": "CRP is a marker of inflammation, which is associated with CI in MHD patients.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689383" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may affect insulin's neuroprotective roles.", "mechanism": "Insulin resistance and impaired signaling are implicated in Alzheimer's pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects insulin's half-life and receptor binding.", "mechanism": "Deficiency or resistance to insulin causes diabetes.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates APP cleavage and amyloid-beta production.", "mechanism": "APP processing leads to amyloid-beta accumulation, a hallmark of Alzheimer's.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation is essential for receptor function.", "mechanism": "Defective insulin receptor signaling leads to insulin resistance.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12689383" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "EGFR is N-glycosylated, which affects ligand binding and receptor activation.", "mechanism": "EGFR mutations drive tumorigenesis and are targeted by tyrosine kinase inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689392" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "NTRK2 is N-glycosylated, influencing receptor stability and signaling.", "mechanism": "NTRK2 gene fusions lead to overexpression/activation of TrkB, driving oncogenic signaling.", "protein": "NTRK2 (TrkB)", "relationship_type": "causal", "source_pmcid": "PMC12689392" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may affect inhibitor binding and receptor trafficking.", "mechanism": "NTRK2 fusions are actionable targets for TRK inhibitors.", "protein": "NTRK2 (TrkB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689392" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "N-glycosylation modulates EGFR function and drug response.", "mechanism": "EGFR mutations are diagnostic and predictive biomarkers for targeted therapy.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689392" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "MET is N-glycosylated, affecting receptor maturation and signaling.", "mechanism": "MET amplification is a resistance mechanism to EGFR-TKIs and targetable by MET inhibitors.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689392" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "FGFR1 is N-glycosylated, influencing ligand binding and receptor function.", "mechanism": "FGFR1 mutations may contribute to tumor progression and represent a potential target.", "protein": "FGFR1", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation a", "gene_name": "FGFR1", "glycan_count": 15, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G08293MJ", "G80920RR", "G84452RH", "G62765YT", "G00912UN", "G22310AV", "G37881RL", "G48414YA", "G56784JY", "G59536GA", "G59626AS", "G70101JE", "G83460ZZ", "G47518TP", "G49108TO" ], "uniprot_id": "P11362" }, "relationship_type": "potential_therapeutic_target", "source_pmcid": "PMC12689392" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "PD-L1 is N-glycosylated, which stabilizes the protein and modulates immune evasion.", "mechanism": "PD-L1 expression predicts response to immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689392" }, { "confidence": "medium", "disease": "Liver metastasis of lung adenocarcinoma", "glycan_involvement": "N-glycosylation may affect metastatic potential via receptor signaling.", "mechanism": "Emergence of NTRK2 fusion in metastasis may drive progression and resistance.", "protein": "NTRK2 (TrkB)", "relationship_type": "causal", "source_pmcid": "PMC12689392" }, { "confidence": "medium", "disease": "Brain metastasis of lung adenocarcinoma", "glycan_involvement": "Glycosylation may influence blood-brain barrier crossing and receptor function.", "mechanism": "EGFR mutations contribute to metastatic spread and survival in brain tissue.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12689392" }, { "confidence": "low", "disease": "Liver metastasis of lung adenocarcinoma", "glycan_involvement": "Glypican-3 is a proteoglycan; glycosylation is essential for its cell surface localization.", "mechanism": "Weak expression in metastasis may aid differential diagnosis.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689392" }, { "confidence": "high", "disease": "Acute Ischemic Stroke", "glycan_involvement": "Glycosylation is essential for proper folding and surface expression of IIb/IIIa.", "mechanism": "Targeted by eptifibatide to inhibit platelet aggregation during mechanical thrombectomy.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689398" }, { "confidence": "high", "disease": "Acute Ischemic Stroke", "glycan_involvement": "Acts on glycoprotein IIb/IIIa; does not itself contain glycans.", "mechanism": "Used as rescue therapy to inhibit glycoprotein IIb/IIIa, improving recanalization rates after failed thrombectomy.", "protein": "Eptifibatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12689398" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "Inhibition reduces platelet aggregation and thrombus formation.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689398" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "Targets glycoprotein IIb/IIIa.", "mechanism": "Administered with fibrinolytics to inhibit platelet aggregation via glycoprotein IIb/IIIa blockade.", "protein": "Eptifibatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Acute Stent Thrombosis", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Inhibition prevents platelet-mediated stent thrombosis.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Acute Stent Thrombosis", "glycan_involvement": "Acts on glycoprotein IIb/IIIa.", "mechanism": "Used to prevent or treat acute stent thrombosis by inhibiting glycoprotein IIb/IIIa.", "protein": "Eptifibatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Atherosclerotic Stenosis", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "Inhibition reduces risk of rethrombosis during endovascular procedures.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Atherosclerotic Stenosis", "glycan_involvement": "Targets glycoprotein IIb/IIIa.", "mechanism": "Administered to prevent rethrombosis by blocking glycoprotein IIb/IIIa.", "protein": "Eptifibatide", "relationship_type": "therapeutic", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Intracerebral Hemorrhage", "glycan_involvement": "Indirect, via inhibition of glycoprotein IIb/IIIa.", "mechanism": "No significant increase in risk of symptomatic intracerebral hemorrhage when used as rescue therapy.", "protein": "Eptifibatide", "relationship_type": "protective", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Intracerebral Hemorrhage", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "Platelet aggregation via IIb/IIIa may contribute to thrombotic complications; inhibition does not significantly increase hemorrhage risk.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC12689398" }, { "confidence": "medium", "disease": "Post-stroke depression (PSD)", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP reflects inflammation linked to PSD risk after stroke.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation affects platelet adhesion and aggregation.", "mechanism": "Platelet glycoproteins mediate thrombosis, contributing to stroke onset.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12689410" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDLR N-glycosylation is essential for receptor function.", "mechanism": "Statins upregulate LDLR, lowering LDL cholesterol and reducing dyslipidemia.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation modulates HDL function and anti-inflammatory properties.", "mechanism": "HDL glycoproteins promote cholesterol efflux, reducing stroke risk.", "protein": "High-density lipoprotein (HDL) associated glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Low testosterone", "glycan_involvement": "SHBG glycosylation influences hormone binding.", "mechanism": "Statins may alter SHBG levels, affecting testosterone bioavailability.", "protein": "Testosterone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "IL-6 glycosylation affects receptor binding and signaling.", "mechanism": "IL-6 drives post-stroke inflammation, contributing to PSD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates cytokine activity.", "mechanism": "TNF-\u03b1 mediates neuroinflammation, increasing PSD risk.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12689410" }, { "confidence": "low", "disease": "Renal insufficiency", "glycan_involvement": "Glycosylation changes impact transferrin clearance.", "mechanism": "Altered transferrin glycosylation reflects renal dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "ApoB glycosylation affects lipoprotein metabolism.", "mechanism": "ApoB levels indicate LDL particle number, linked to dyslipidemia.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12689410" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "AGP glycosylation modulates immunomodulatory functions.", "mechanism": "AGP is an acute-phase reactant elevated in inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689410" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated AST indicates hepatocellular injury following HFCS exposure.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates ALT secretion and activity.", "mechanism": "ALT elevation reflects liver cell damage in response to HFCS-induced steatosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation is essential for GGT membrane localization.", "mechanism": "Increased GGT is associated with oxidative stress and liver dysfunction after HFCS intake.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "N-glycosylation influences albumin stability and transport.", "mechanism": "Decreased albumin may indicate impaired liver synthetic function in MASLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "N-glycosylation required for prothrombin secretion.", "mechanism": "Altered prothrombin time reflects hepatic synthetic dysfunction in MASLD.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects insulin receptor binding and clearance.", "mechanism": "HFCS intake reduces insulin sensitivity, promoting insulin resistance.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation regulates uric acid transporter function.", "mechanism": "HFCS increases uric acid, contributing to hepatic stress and steatosis.", "protein": "Uric acid (transporters)", "relationship_type": "mechanistic mediator", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates lactate transporter activity.", "mechanism": "Elevated lactate links HFCS metabolism to hepatic injury.", "protein": "Lactate (transporters)", "relationship_type": "mechanistic mediator", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation impacts AST serum stability.", "mechanism": "AST elevation is a marker of NAFLD progression after HFCS exposure.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects ALT activity and detection.", "mechanism": "ALT is a sensitive indicator of NAFLD in the context of HFCS-induced liver injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689413" }, { "confidence": "high", "disease": "MACCEs", "glycan_involvement": "Albumin glycosylation status may affect stability and function.", "mechanism": "Low serum albumin reflects malnutrition and chronic inflammation, predicting higher MACCEs risk.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12689418" }, { "confidence": "high", "disease": "Chronic total occlusion (CTO)", "glycan_involvement": "Altered glycosylation may impact albumin's vascular protective effects.", "mechanism": "Hypoalbuminemia is associated with poor outcomes in CTO patients post-PCI.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12689418" }, { "confidence": "medium", "disease": "MACCEs", "glycan_involvement": "Glycosylation modulates lymphocyte trafficking and function.", "mechanism": "Low lymphocyte count indicates impaired immune status, increasing MACCEs risk.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12689418" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "IL-6 glycosylation affects receptor binding and signaling.", "mechanism": "IL-6 suppresses albumin synthesis and promotes inflammation, leading to endothelial injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12689418" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 stability and activity.", "mechanism": "TNF-\u03b1 suppresses albumin synthesis and promotes muscle wasting.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12689418" }, { "confidence": "medium", "disease": "In-stent restenosis", "glycan_involvement": "VEGF glycosylation is essential for angiogenic activity.", "mechanism": "VEGF promotes collateral vessel formation; suppressed by chronic inflammation.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "protective", "source_pmcid": "PMC12689418" }, { "confidence": "low", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation may regulate STAT3 nuclear translocation.", "mechanism": "Sustained STAT3 activation inhibits endothelial cell proliferation and migration.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC12689418" }, { "confidence": "low", "disease": "Systemic inflammation", "glycan_involvement": "IL-10 glycosylation affects anti-inflammatory potency.", "mechanism": "IL-10 secretion by muscle contraction reduces inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12689418" }, { "confidence": "medium", "disease": "MACCEs", "glycan_involvement": "LDL glycosylation influences receptor binding and clearance.", "mechanism": "Elevated LDL-C is associated with increased MACCEs risk.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12689418" }, { "confidence": "low", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation may affect NF-\u03baB pathway activation.", "mechanism": "NF-\u03baB activation drives inflammatory signaling, impairing endothelial repair.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12689418" }, { "confidence": "high", "disease": "Acute pericarditis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "CRP is markedly elevated during SLE-associated acute pericarditis, reflecting inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates CRP's immune recognition.", "mechanism": "CRP is usually normal or mildly elevated in SLE, but rises significantly with serositis (e.g., pericarditis).", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation of \u03b22GPI influences autoantibody binding and pathogenicity.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I promote thrombosis in APS.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Thrombotic events", "glycan_involvement": "Targets glycosylated domains of \u03b22GPI.", "mechanism": "Presence of anti-\u03b22GPI antibodies is associated with increased risk of thrombosis in SLE/APS.", "protein": "Anti-\u03b22-glycoprotein I antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Thrombotic events", "glycan_involvement": "Recognizes glycoprotein-phospholipid complexes.", "mechanism": "LA positivity is linked to higher risk of thrombosis in SLE and APS.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12689497" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "C3 is a glycoprotein; glycosylation affects complement activation.", "mechanism": "Low C3 indicates active SLE; normal in this case during flare.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "C4 glycosylation modulates immune complex clearance.", "mechanism": "Low C4 is a marker of SLE activity; normal in this case.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "ANA are autoantibodies (glycoproteins) with glycosylation affecting immune complex formation.", "mechanism": "ANA positivity is diagnostic for SLE.", "protein": "Antinuclear antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Autoantibody glycosylation may affect pathogenicity.", "mechanism": "Highly specific for SLE diagnosis.", "protein": "Anti-Smith antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12689497" }, { "confidence": "medium", "disease": "Lupus nephritis", "glycan_involvement": "Glycosylation of IgG influences renal deposition and inflammation.", "mechanism": "Anti-dsDNA antibodies are associated with lupus nephritis.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12689497" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "HA is a glycoprotein; glycosylation affects antigenicity and immune evasion.", "mechanism": "HA is the main target of neutralizing antibodies induced by vaccines, mediating viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Severe influenza-associated morbidity", "glycan_involvement": "Glycosylation modulates immune recognition and vaccine efficacy.", "mechanism": "HA-based vaccines reduce morbidity by inducing neutralizing antibodies.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Influenza-associated mortality", "glycan_involvement": "Glycosylation sites can shield epitopes, affecting protection.", "mechanism": "HA-targeted immunity prevents lethal infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "NP is not a glycoprotein; no glycan involvement.", "mechanism": "NP is targeted by T cell responses; synthetic NP vaccines induce cellular immunity.", "protein": "Nucleoprotein (NP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Severe influenza-associated morbidity", "glycan_involvement": "Not applicable.", "mechanism": "NP-based vaccines reduce lung pathology and inflammation via T cell responses.", "protein": "Nucleoprotein (NP)", "relationship_type": "protective", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Influenza-associated mortality", "glycan_involvement": "Not applicable.", "mechanism": "NP-based vaccines protect against death in lethal challenge models.", "protein": "Nucleoprotein (NP)", "relationship_type": "protective", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Glycosylation patterns influence antigenic drift.", "mechanism": "HA is used for serological diagnosis and vaccine strain selection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Glycosylation affects receptor binding and host range.", "mechanism": "HA mediates viral entry into host cells.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Severe influenza-associated morbidity", "glycan_involvement": "Addition/removal of glycosylation sites alters immune escape.", "mechanism": "HA antigenic drift can lead to vaccine escape and increased morbidity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689538" }, { "confidence": "medium", "disease": "Influenza-associated mortality", "glycan_involvement": "Glycosylation shields or exposes virulence determinants.", "mechanism": "HA mutations and glycosylation changes can increase virulence.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689538" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Targeted by antiphospholipid antibodies, leading to endothelial activation, complement activation, and placental injury.", "protein": "\u03b22-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation may affect membrane binding.", "mechanism": "Forms anticoagulant shield on syncytiotrophoblasts; displaced by aPL, increasing thrombosis risk.", "protein": "Annexin V", "relationship_type": "protective", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation influences complement activation and deposition.", "mechanism": "Deposition at maternal-fetal interface correlates with fetal loss and placental injury.", "protein": "Complement C4d", "relationship_type": "biomarker", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation modulates complement activity.", "mechanism": "Amplifies complement cascade, leading to inflammation and placental damage.", "protein": "Complement C3b", "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation affects MAC assembly and function.", "mechanism": "Direct cell injury at maternal-fetal interface, driving placental dysfunction.", "protein": "Complement C5b-9 (MAC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "medium", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation required for surface expression and function.", "mechanism": "Regulates complement activation; loss increases placental complement deposition and inflammation.", "protein": "Membrane cofactor protein (CD46)", "relationship_type": "protective", "source_pmcid": "PMC12689542" }, { "confidence": "medium", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation essential for membrane localization.", "mechanism": "Restrains complement activation; reduced expression linked to adverse outcomes.", "protein": "Decay-accelerating factor (CD55)", "relationship_type": "protective", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Reduced fucosylation/sialylation increases Fc\u03b3R binding and pathogenicity.", "mechanism": "Autoantibodies (aPL) drive inflammation, complement activation, and thrombosis.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "medium", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation critical for selectin binding.", "mechanism": "Facilitates neutrophil adhesion and NET formation, promoting thrombosis.", "protein": "P-selectin glycoprotein ligand-1 (PSGL-1)", "protein_enriched": { "function": "Plays a role in odontogenesis", "gene_name": "SSUH2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2M2" }, "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "medium", "disease": "Obstetric Antiphospholipid Syndrome (OAPS)", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Dysregulation impairs trophoblast function and exacerbates placental injury.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12689542" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Truncated O-glycans (Tn/STn) on MUC1 promote immune evasion and invasiveness.", "mechanism": "Aberrant O-glycosylation (Tn/STn) on MUC1 correlates with tumor progression, metastasis, and poor prognosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12689565" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "STn modification on MUC16 drives immune suppression and correlates with poor survival.", "mechanism": "MUC16-STn complex interacts with immune lectins (Siglec-9, CD206), suppressing anti-tumor immunity.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12689565" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Truncated O-glycosylation leads to exposed Tn antigen on cell surface.", "mechanism": "Tn antigen accumulation (due to COSMC/T-synthase loss) activates EGFR/FAK signaling, promoting proliferation and invasion.", "protein": "Tn antigen", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689565" }, { "confidence": "high", "disease": "Pancreatic cancer (PDAC)", "glycan_involvement": "Terminal sialylation (STn) blocks glycan extension, driving immune suppression.", "mechanism": "STn antigen interacts with Siglec-7/9 on TAMs, promoting angiogenesis and immune evasion.", "protein": "STn antigen", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "O-glycosylation truncation exposes Tn epitope on CD44.", "mechanism": "Tn-modified CD44 detected in COSMC-knockout cells; serves as diagnostic marker for non-MUC1-expressing lung cancers.", "protein": "CD44 (Tn-modified)", "relationship_type": "biomarker", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "STn modification acts as 'molecular glue' for cell-cell interactions.", "mechanism": "STn-MUC5AC binds NECTIN2, enhancing migration and metastasis.", "protein": "MUC5AC (STn-modified)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Tn antigen clusters on TAG-72 serve as diagnostic epitopes.", "mechanism": "CA72-4 detects Tn antigen clusters, used for tumor screening.", "protein": "TAG-72 (CA72-4 antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "Pancreatic cancer (PDAC)", "glycan_involvement": "Glycosylation-dependent interaction with immune cells.", "mechanism": "Anti-Gal-3BP antibody eliminates PDAC cell transfer in vivo.", "protein": "Gal-3BP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "IgA nephropathy", "glycan_involvement": "Aberrant O-glycosylation of IgA1 leads to immune complex formation.", "mechanism": "Protein glycosylation truncation (Tn antigen in IgA1 hinge region) implicated in disease pathogenesis.", "protein": "Tn antigen", "relationship_type": "causal", "source_pmcid": "PMC12689565" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Restoration of O-glycan extension reduces Tn antigen, promoting anti-tumor immunity.", "mechanism": "Upregulation of T-synthase (reducing Tn antigen) inhibits proliferation and enhances CTL response.", "protein": "Tn antigen", "relationship_type": "protective (when T-synthase upregulated)", "source_pmcid": "PMC12689565" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct evidence of IL-32 glycosylation; interacts with glycoprotein receptors.", "mechanism": "IL-32 levels are elevated in HIV infection; modulates immune response and viral replication.", "protein": "Interleukin-32 (IL-32)", "protein_enriched": { "function": "Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules aroun", "gene_name": "NUSAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXS6" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "AIDS", "glycan_involvement": "No direct evidence; effect via immune modulation.", "mechanism": "IL-32 expression is higher in acute and AIDS stages, correlating with disease progression.", "protein": "Interleukin-32 (IL-32)", "protein_enriched": { "function": "Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules aroun", "gene_name": "NUSAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXS6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "HIV-associated cardiovascular disease (CVD)", "glycan_involvement": "No direct evidence; acts via glycoprotein receptors (integrins).", "mechanism": "IL-32 isoforms (\u03b1, \u03b2, \u03b3, \u03b8, D, \u03f5) upregulated in HIV+ individuals with CVD; promotes inflammation, monocyte adhesion, and vascular calcification.", "protein": "Interleukin-32 (IL-32)", "protein_enriched": { "function": "Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules aroun", "gene_name": "NUSAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXS6" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "No direct evidence; effect via immune cell modulation.", "mechanism": "IL-32 isoforms (\u03b1, \u03b2, \u03b8, D, \u03f5) correlate with pro-atherogenic mediators and vascular inflammation.", "protein": "Interleukin-32 (IL-32)", "protein_enriched": { "function": "Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules aroun", "gene_name": "NUSAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXS6" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "No direct evidence; interacts with glycoprotein receptors.", "mechanism": "IL-32\u03b3 can reactivate latent HIV in CD4+ T cells, suggesting use in 'shock and kill' strategies.", "protein": "Interleukin-32\u03b3 (IL-32\u03b3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct evidence; effect via immune modulation.", "mechanism": "IL-32\u03b3 suppresses HIV entry and replication by downregulating CD4/CCR5 and upregulating antiviral genes.", "protein": "Interleukin-32\u03b3 (IL-32\u03b3)", "relationship_type": "protective", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "HIV-associated CVD", "glycan_involvement": "No direct evidence; acts via glycoprotein receptors.", "mechanism": "IL-32\u03b2 promotes monocyte polarization to inflammatory phenotype, increases pro-atherogenic cytokines.", "protein": "Interleukin-32\u03b2 (IL-32\u03b2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "medium", "disease": "HIV-associated CVD", "glycan_involvement": "Integrin is a glycoprotein; glycosylation required for function.", "mechanism": "IL-32 interacts with integrin \u03b1v\u03b23 to modulate endothelial and immune cell function, promoting inflammation.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (as receptor)", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation modulates immune checkpoint function.", "mechanism": "IL-32\u03b3 upregulates PD-L1 in macrophages, contributing to immune evasion and HIV persistence.", "protein": "Programmed death-ligand 1 (PD-L1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "IL-32\u03b3 induces IDO, promoting Treg expansion and immunosuppression, facilitating HIV persistence.", "protein": "Indoleamine 2,3-dioxygenase (IDO)", "protein_enriched": { "function": "Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contrib", "gene_name": "IDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14902" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12689581" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "AMPK activation restores energy homeostasis, reduces lipid accumulation, and suppresses inflammation in NAFLD.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "SREBP-1c is glycosylated; glycosylation may affect stability and nuclear translocation.", "mechanism": "SREBP-1c upregulation increases lipogenesis, contributing to hepatic lipid accumulation in NAFLD.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "ACC is glycosylated; glycosylation may modulate enzyme activity.", "mechanism": "AMPK-mediated phosphorylation of ACC inhibits fatty acid synthesis, reducing NAFLD progression.", "protein": "ACC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "FASN is glycosylated; glycosylation may affect enzymatic function.", "mechanism": "FASN promotes de novo lipogenesis; its upregulation is linked to NAFLD.", "protein": "FASN", "relationship_type": "causal", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "SCD1 is glycosylated; glycosylation may influence activity.", "mechanism": "SCD1 increases monounsaturated fatty acid synthesis, promoting hepatic steatosis in NAFLD.", "protein": "SCD1", "relationship_type": "causal", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "PPAR\u03b1 is glycosylated; glycosylation may affect receptor function.", "mechanism": "PPAR\u03b1 activation enhances fatty acid oxidation, reducing hepatic lipid accumulation in NAFLD.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Nrf2 is glycosylated; glycosylation may regulate nuclear translocation.", "mechanism": "Nrf2 activation upregulates antioxidant enzymes, mitigating oxidative stress in NAFLD.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12689597" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "ULK1 is glycosylated; glycosylation may affect autophagy initiation.", "mechanism": "AMPK-mediated ULK1 activation promotes autophagy and lipophagy, reducing hepatic lipid droplets in NAFLD.", "protein": "ULK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "NF-\u03baB is glycosylated; glycosylation may modulate transcriptional activity.", "mechanism": "NF-\u03baB activation drives hepatic inflammation, exacerbating NAFLD progression.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12689597" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "NLRP3 is glycosylated; glycosylation may affect inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation promotes inflammatory cytokine release, contributing to NAFLD pathology.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12689597" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Mucin glycan degradation by glycoprotein enzymes.", "mechanism": "Over-representation and mucin-degrading activity may enhance mucosal inflammation and promote MS pathology.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "causal", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Potential modulation of host glycoproteins and mucosal immunity.", "mechanism": "Elevated Collinsella abundance associated with worse MS course and radiological progression.", "protein": "Collinsella spp.", "relationship_type": "biomarker", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Fermentation of dietary glycans to SCFAs.", "mechanism": "SCFA production (including butyrate) may confer anti-inflammatory effects and support regulatory T cell differentiation.", "protein": "Phocaeicola (Parabacteroides)", "relationship_type": "protective", "source_pmcid": "PMC12689865" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Fermentation of host and dietary glycans to butyrate.", "mechanism": "Butyrate promotes Treg differentiation and modulates NK cell cytotoxicity, reducing autoimmune inflammation.", "protein": "Butyrate-producing bacteria", "relationship_type": "protective", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycan fermentation and SCFA production.", "mechanism": "Increase in Bacteroidota phylum post-FMT associated with clinical improvement.", "protein": "Unclassified Bacteroidales", "relationship_type": "protective", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycan fermentation.", "mechanism": "Increase post-FMT may contribute to SCFA (butyrate) production and anti-inflammatory effects.", "protein": "Unclassified Eubacteriales", "relationship_type": "protective", "source_pmcid": "PMC12689865" }, { "confidence": "low", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation may affect enzyme stability and function.", "mechanism": "Reduced enzymatic activity predisposes to intestinal inflammation and food intolerance.", "protein": "MTHFR", "relationship_type": "biomarker", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Food intolerance", "glycan_involvement": "Glycosylation of MHC II affects antigen presentation.", "mechanism": "Positive haplotype predisposes to immune-mediated food intolerance.", "protein": "HLA-DQ7", "relationship_type": "causal", "source_pmcid": "PMC12689865" }, { "confidence": "high", "disease": "Clostridioides difficile infection", "glycan_involvement": "Glycosylation critical for toxin activity.", "mechanism": "Toxin glycoproteins disrupt intestinal epithelial integrity.", "protein": "Clostridioides difficile toxin A/B", "relationship_type": "causal", "source_pmcid": "PMC12689865" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation may modulate stability and immune recognition.", "mechanism": "Elevated fecal calprotectin indicates neutrophil-driven inflammation.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12689865" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBsAg is a heavily glycosylated viral envelope protein; glycosylation affects antigenicity and immune recognition.", "mechanism": "HBsAg level reflects HBV replication and transcriptional activity; lower levels at week 24 predict higher likelihood of seroclearance after PEG-IFN\u03b1-2b therapy.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBeAg is glycosylated, influencing immune tolerance and recognition.", "mechanism": "Loss of HBeAg and appearance of HBeAb (seroconversion) at week 24 predicts favorable immune response and higher chance of HBsAg seroclearance.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Targets glycosylated HBeAg; glycan structures may affect antibody binding.", "mechanism": "Presence of HBeAb at week 24 indicates immune activation and is associated with HBsAg seroclearance.", "protein": "Hepatitis B e antibody (HBeAb)", "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Low baseline GGT is associated with reduced liver inflammation and better antiviral immune response, predicting higher HBsAg seroclearance.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Targets core antigen, which may be glycosylated; glycan status can affect immune recognition.", "mechanism": "Baseline HBcAb levels and their change over 24 weeks are included in predictive models for HBsAg seroclearance.", "protein": "Hepatitis B core antibody (HBcAb)", "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "low", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "ALT at week 24 is a supportive predictor in models for HBsAg seroclearance, reflecting liver inflammation.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "low", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "ALP is glycosylated; glycosylation affects enzyme activity and stability.", "mechanism": "ALP at week 24 is a minor predictor in models for HBsAg seroclearance.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "low", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "DBIL at week 24 is a minor predictor in models for HBsAg seroclearance.", "protein": "Direct bilirubin (DBIL)", "relationship_type": "biomarker", "source_pmcid": "PMC12689909" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of HBsAg may affect immune escape and chronicity.", "mechanism": "Persistent HBsAg positivity increases risk of progression to HCC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12689909" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may modulate immune response and fibrogenesis.", "mechanism": "Persistent HBsAg positivity increases risk of progression to cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12689909" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "Not directly addressed; INTS10 is a putative glycoprotein.", "mechanism": "INTS10 inhibits HBV replication, especially in HBeAg-positive patients, via IRF3-dependent pathway.", "protein": "INTS10", "relationship_type": "protective", "source_pmcid": "PMC12689913" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "No direct glycosylation role for IRF3.", "mechanism": "IRF3 activation suppresses HBV replication by inducing interferon-stimulated genes.", "protein": "IRF3", "protein_enriched": { "function": "Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049", "gene_name": "IRF3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14653" }, "relationship_type": "protective", "source_pmcid": "PMC12689913" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not specified.", "mechanism": "Reduced INTS10 expression and SNPs are associated with increased risk of HBV-related HCC.", "protein": "INTS10", "relationship_type": "protective", "source_pmcid": "PMC12689913" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "HBeAg is a secreted glycoprotein; glycosylation required for secretion.", "mechanism": "HBeAg status modulates the antiviral effects of INTS10 and IRF3; high HBeAg correlates with lower INTS10/IRF3 and higher viral load.", "protein": "HBeAg", "relationship_type": "biomarker", "source_pmcid": "PMC12689913" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation critical for secretion and immune evasion.", "mechanism": "HBsAg levels inversely correlate with INTS10 in HBeAg-positive patients.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689913" }, { "confidence": "medium", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "NTCP is a glycoprotein; glycosylation affects membrane localization and function.", "mechanism": "NTCP is the hepatic receptor for HBV; altered bile acid uptake in HBV infection.", "protein": "NTCP (SLC10A1)", "relationship_type": "causal", "source_pmcid": "PMC12689913" }, { "confidence": "medium", "disease": "HBV-related metabolic disorders", "glycan_involvement": "Not specified.", "mechanism": "INTS10 expression inversely correlates with total bile acid (TBA) levels in HBeAg-positive CHB, suggesting a role in metabolic regulation.", "protein": "INTS10", "relationship_type": "protective", "source_pmcid": "PMC12689913" }, { "confidence": "high", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "Not specified.", "mechanism": "Lower INTS10 expression is associated with higher HBV DNA, HBeAg, HBsAg, and TBA in HBeAg-positive patients.", "protein": "INTS10", "relationship_type": "biomarker", "source_pmcid": "PMC12689913" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation role.", "mechanism": "IRF3 pathway activation may reduce HBV persistence and HCC risk.", "protein": "IRF3", "protein_enriched": { "function": "Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049", "gene_name": "IRF3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14653" }, "relationship_type": "protective", "source_pmcid": "PMC12689913" }, { "confidence": "medium", "disease": "HBV-related metabolic disorders", "glycan_involvement": "NTCP glycosylation modulates function.", "mechanism": "HBV infection alters NTCP-mediated bile acid uptake, contributing to metabolic disturbances.", "protein": "NTCP (SLC10A1)", "relationship_type": "causal", "source_pmcid": "PMC12689913" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "LILRB2 is a transmembrane glycoprotein; glycosylation likely affects receptor stability and ligand interactions.", "mechanism": "High LILRB2 expression correlates with advanced TNM stage, lymph node metastasis, and poor prognosis; inhibits immune cell activity and promotes immune evasion.", "protein": "LILRB2", "relationship_type": "biomarker", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may regulate ligand binding and immune modulation.", "mechanism": "LILRB2 modulates the tumor immune microenvironment and is associated with immune checkpoint pathways.", "protein": "LILRB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "As a glycoprotein, glycosylation may affect its immune regulatory function.", "mechanism": "LILRB2 contributes to immune suppression and tumor progression.", "protein": "LILRB2", "relationship_type": "causal", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "Glycosylation may influence receptor-ligand interactions.", "mechanism": "LILRB2 upregulation promotes immune evasion and tumor advancement.", "protein": "LILRB2", "relationship_type": "causal", "source_pmcid": "PMC12689926" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "APE1 is not a glycoprotein; no glycan involvement.", "mechanism": "High APE1 expression is associated with advanced stage, larger tumor size, lymph node metastasis, and poor prognosis.", "protein": "APE1", "relationship_type": "biomarker", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not applicable.", "mechanism": "APE1 regulates DNA repair and redox signaling, influencing tumor growth and chemoresistance.", "protein": "APE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689926" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may enhance biomarker detectability in serum.", "mechanism": "Combined high LILRB2 and APE1 expression predicts poorer survival than either marker alone.", "protein": "LILRB2", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may modulate immune cell interactions.", "mechanism": "LILRB2 overexpression is associated with decreased CD3+/CD8+ T cells and increased FOXP3+ Tregs in the tumor microenvironment.", "protein": "LILRB2", "relationship_type": "causal", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect microenvironmental localization.", "mechanism": "LILRB2 expression is higher in microsatellite-stable (MSS) CRC, indicating a myeloid immunosuppression\u2013dominant microenvironment.", "protein": "LILRB2", "relationship_type": "biomarker", "source_pmcid": "PMC12689926" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not applicable.", "mechanism": "APE1 expression is higher in MSI-high tumors, reflecting adaptive DNA repair under immune pressure.", "protein": "APE1", "relationship_type": "biomarker", "source_pmcid": "PMC12689926" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "C3 is a glycoprotein; glycosylation is required for secretion and stability but not directly implicated in the resistance mechanism described.", "mechanism": "C3 gain-of-function mutations (especially in MG-ring) cause dysregulation of complement activation, leading to persistent hemolysis and resistance to complement inhibitors.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "CD55 is GPI-anchored and glycosylated; loss of GPI anchor (a glycan modification) is central to pathogenesis.", "mechanism": "Loss of GPI-anchored CD55 due to PIGA mutation leads to increased complement activation on erythrocytes.", "protein": "CD55 (Decay-Accelerating Factor)", "protein_enriched": { "function": "This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf wi", "gene_name": "CD55", "glycan_count": 15, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00912UN", "G06356OH", "G08918WF", "G12313PD", "G25451PN", "G40574BA", "G46503DX", "G48414YA", "G59626AS", "G65184UU", "G72790NZ", "G75983OB", "G84452RH" ], "uniprot_id": "P08174" }, "relationship_type": "causal", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "CD59 is GPI-anchored and glycosylated; loss of GPI anchor is critical.", "mechanism": "Loss of GPI-anchored CD59 increases susceptibility to complement-mediated lysis.", "protein": "CD59", "protein_enriched": { "function": "Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation (PubMed:11882685, PubMed:1698710, PubMed:2475111, PubMed:24", "gene_name": "CD59", "glycan_count": 226, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G51287LK", "G60554YG", "G74724QE", "G31685JQ", "G12728EY", "G22625SJ", "G47448YK", "G49108TO", "G00176HZ", "G00273SJ", "G00912UN", "G02030ZB", "G02315DX", "G02528FI", "G02815KT", "G03382KH", "G04657PL", "G05962QB", "G06247RL", "G06290IR", "G06330RB", "G06356OH", "G07246CJ", "G07483YN", "G07755XJ", "G08520NM", "G08918WF", "G09831WQ", "G10846ZT", "G11629QQ", "G12341GU", "G12793SR", "G13131HA", "G13191RB", "G13728QT", "G13749ZZ", "G14456RI", "G14882EB", "G14972EH", "G14994KB", "G15169WU", "G15488CF", "G16768LX", "G16828VN", "G17208MA", "G18647XP", "G20312EM", "G22310AV", "G22768VO", "G23133OF", "G23863VK", "G23984SE", "G24835MQ", "G24954UD", "G25418HZ", "G27058EU", "G27126ED", "G27919IH", "G29501UT", "G30740WO", "G30751OD", "G30799SW", "G31596VW", "G31615DN", "G31852PQ", "G32788FZ", "G34617SM", "G34989PA", "G36013ES", "G36134VO", "G36191CD", "G36379GD", "G37412TK", "G37773JL", "G37818NZ", "G39064KU", "G39213VZ", "G39595FH", "G40124HY", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41405QQ", "G42124LM", "G43223CG", "G43669FQ", "G44173IH", "G44215PV", "G44413JJ", "G44778BV", "G45395BF", "G45883VE", "G46487SG", "G46665ZP", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G48414YA", "G50120TH", "G50427EO", "G50856PC", "G51413EV", "G52114WE", "G52358QA", "G52589SM", "G55220VL", "G56087PR", "G56518TU", "G57557NS", "G57776ZS", "G57888GL", "G57939IT", "G58596DI", "G58598BO", "G58667NI", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G61207RZ", "G61256FT", "G61505ZR", "G61806WR", "G62765YT", "G63628AV", "G63640QH", "G63889NK", "G64227LK", "G64394MX", "G64527OM", "G65019XG", "G65092SV", "G66621EA", "G66760KM", "G67164EE", "G67900CJ", "G68833MP", "G69521XL", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71146HJ", "G71463BG", "G71919QK", "G72667IM", "G72797UR", "G72886NH", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77023TY", "G77149EE", "G77669RF", "G78059CC", "G78502KD", "G78649WQ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80858MF", "G80920RR", "G80966KZ", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82348BZ", "G82443XX", "G82830MN", "G83229XP", "G83633GK", "G83646BJ", "G84452RH", "G85269DF", "G85282JO", "G85737WG", "G86182NS", "G86226EA", "G86234IN", "G86357DX", "G86408JD", "G86795LJ", "G86880BF", "G87123QX", "G87618BG", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G90717TP", "G91473PK", "G91636VS", "G92062TF", "G92081HT", "G92135MA", "G92275SC", "G93141AZ", "G93993PD", "G94470IW", "G94831VI", "G95177YH", "G95865ZB", "G95977AE", "G98611JV", "G57321FI", "G01079KY", "G16389EC", "G31544HA", "G46687AB", "G50045TK", "G51519NL", "G71269BI", "G75727PF", "G80218BM", "G83461WR", "G90093AU" ], "uniprot_id": "P13987" }, "relationship_type": "causal", "source_pmcid": "PMC12689931" }, { "confidence": "medium", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "FH is a glycoprotein; glycosylation affects stability but not directly implicated in described mechanism.", "mechanism": "Rare FH variants can exacerbate complement dysregulation and hemolysis in PNH.", "protein": "Complement Factor H", "relationship_type": "modifier", "source_pmcid": "PMC12689931" }, { "confidence": "medium", "disease": "Atypical Hemolytic Uremic Syndrome (aHUS)", "glycan_involvement": "C3 glycosylation is required for function but not directly implicated in mechanism.", "mechanism": "C3 gain-of-function mutations (e.g., R505H) are linked to complement dysregulation in aHUS.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12689931" }, { "confidence": "medium", "disease": "C3 Glomerulopathy (C3G)", "glycan_involvement": "C3 glycosylation is required for function but not directly implicated in mechanism.", "mechanism": "C3 gain-of-function mutations in MG-ring domains contribute to complement activation in C3G.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12689931" }, { "confidence": "medium", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "CR1 is a glycoprotein; glycosylation not directly discussed in mechanism.", "mechanism": "Low-expression CR1 alleles increase C3 opsonization and extravascular hemolysis under C5 inhibition.", "protein": "Complement Receptor 1 (CR1)", "relationship_type": "modifier", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "C3 glycosylation is required for secretion and function.", "mechanism": "C3 is targeted by pegcetacoplan; MG-ring mutations reduce drug binding and efficacy.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "C3 glycosylation is required for function.", "mechanism": "C3 fragment deposition on erythrocytes is a biomarker of extravascular hemolysis.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Paroxysmal Nocturnal Hemoglobinuria (PNH)", "glycan_involvement": "C3 glycosylation is required for function.", "mechanism": "C3 MG-ring mutations confer resistance to pegcetacoplan, impacting personalized therapy.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689931" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Addition of glucose to hemoglobin (glycation, not enzymatic glycosylation).", "mechanism": "Reflects chronic hyperglycemia via non-enzymatic glycation of hemoglobin.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12689944" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation of ApoB-100 modulates LDL clearance.", "mechanism": "Elevated LDL-C promotes atherosclerosis; glycosylation of ApoB-100 affects LDL metabolism.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation of insulin receptor modulates sensitivity.", "mechanism": "Insulin resistance and impaired secretion are central to T2DM; glycosylation affects insulin receptor signaling.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation of GLP-1 receptor influences function.", "mechanism": "GLP-1 receptor agonists improve glycemic control; receptor glycosylation affects ligand binding.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation required for DPP-4 stability and activity.", "mechanism": "DPP-4 inhibitors prolong incretin action, improving glycemia; DPP-4 is a glycoprotein.", "protein": "DPP-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Metabolic inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor interaction.", "mechanism": "TNF-\u03b1 promotes insulin resistance and inflammation in metabolic disease.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Metabolic inflammation", "glycan_involvement": "Glycosylation modulates IL-6 stability and activity.", "mechanism": "IL-6 drives inflammatory signaling in diabetes and obesity.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Metabolic inflammation", "glycan_involvement": "Glycosylation regulates MCP-1 secretion.", "mechanism": "MCP-1 recruits monocytes, contributing to tissue inflammation in diabetes.", "protein": "MCP-1 (CCL2)", "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Infection susceptibility", "glycan_involvement": "N-glycosylation of TLR4 modulates ligand binding and signaling.", "mechanism": "TLR4 mediates innate immune responses; altered glycosylation affects pathogen recognition.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "medium", "disease": "Metabolic inflammation", "glycan_involvement": "N-glycosylation required for CD14 function.", "mechanism": "CD14 is a co-receptor for LPS; glycosylation affects immune activation in diabetes.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC12689944" }, { "confidence": "high", "disease": "Sarcoidosis", "glycan_involvement": "ACE is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated serum ACE levels are associated with active sarcoidosis due to increased production by epithelioid cells in granulomas.", "protein": "Angiotensin-converting enzyme", "relationship_type": "biomarker", "source_pmcid": "PMC12689946" }, { "confidence": "high", "disease": "Abdominal sarcoidosis", "glycan_involvement": "Glycosylation of ACE may influence its detection and function as a biomarker.", "mechanism": "Serum ACE is elevated in abdominal sarcoidosis, supporting diagnosis when combined with clinical findings.", "protein": "Angiotensin-converting enzyme", "relationship_type": "biomarker", "source_pmcid": "PMC12689946" }, { "confidence": "medium", "disease": "Hepatic sarcoidosis", "glycan_involvement": "Glycosylation modulates ACE secretion and serum half-life.", "mechanism": "Elevated ACE levels are seen in hepatic involvement of sarcoidosis.", "protein": "Angiotensin-converting enzyme", "relationship_type": "biomarker", "source_pmcid": "PMC12689946" }, { "confidence": "medium", "disease": "Splenic sarcoidosis", "glycan_involvement": "Glycosylation may affect ACE's immunogenicity and clearance.", "mechanism": "Serum ACE may be elevated in splenic sarcoidosis, reflecting granuloma burden.", "protein": "Angiotensin-converting enzyme", "relationship_type": "biomarker", "source_pmcid": "PMC12689946" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects its immune recognition.", "mechanism": "Exosomal PD-L1 mediates systemic immunosuppression by engaging PD-1 on T cells, contributing to immune evasion and resistance to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Exosomal TGF-\u03b21 suppresses lymphocyte proliferation and downregulates NKG2D on NK/CD8+ T cells, promoting immune escape and tumor progression.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation modulates VEGF stability and receptor interaction.", "mechanism": "Exosomal VEGF promotes angiogenesis and metastatic spread by enhancing endothelial cell proliferation.", "protein": "VEGF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "N-glycosylation critical for antigen presentation.", "mechanism": "Exosomal MHC-I presents tumor antigens, potentially activating cytotoxic T cell responses; downregulation impairs immune recognition.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12689977" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation affects exosome targeting and protein-protein interactions.", "mechanism": "Exosomal CD9 modulates osteoclast differentiation and metastatic tropism; blockade inhibits osteoclastogenesis.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "high", "disease": "Chemoresistant osteosarcoma", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Exosomal P-gp transfer confers multidrug resistance by enhancing drug efflux in recipient cells.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "medium", "disease": "Osteolytic disease", "glycan_involvement": "Glycosylation influences RANKL stability and receptor binding.", "mechanism": "Exosomal RANKL promotes osteoclastogenesis and bone matrix degradation.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation modulates CTLA-4 surface expression.", "mechanism": "CTLA-4 expressed on T cells enables immune escape; blockade enhances CTL activity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "GD2 is a glycosphingolipid antigen; glycan structure is essential for immune recognition.", "mechanism": "GD2 is overexpressed on osteosarcoma cells and targeted by CAR-T therapy.", "protein": "GD2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "medium", "disease": "Metastatic osteosarcoma", "glycan_involvement": "Glycosylation affects ALP-1 stability and immunogenicity.", "mechanism": "ALP-1 is a metastatic osteosarcoma antigen targeted by CAR-T cells for tumor specificity.", "protein": "Alkaline phosphatase 1 (ALP-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689977" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation regulates VE-cadherin stability and cell-cell adhesion.", "mechanism": "Loss of VE-cadherin during EndMT leads to endothelial barrier disruption and vascular remodeling.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation affects CD31-mediated cell adhesion.", "mechanism": "Loss of CD31 during EndMT impairs endothelial integrity and promotes mesenchymal transition.", "protein": "CD31", "relationship_type": "causal", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation modulates VCAM-1 binding to leukocytes.", "mechanism": "Upregulated VCAM-1 on ECs marks endothelial activation and inflammation in PAH.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation is essential for E-selectin ligand recognition.", "mechanism": "Elevated E-selectin on ECs indicates endothelial activation and leukocyte recruitment.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation required for ICAM-1 function.", "mechanism": "ICAM-1 upregulation on ECs facilitates leukocyte adhesion and vascular inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12689994" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation affects gp130 receptor stability and signaling.", "mechanism": "gp130 mediates IL-6 reverse signaling, promoting EC secretion of MCP-1 and inflammation.", "protein": "gp130", "relationship_type": "causal", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation influences ET-1 secretion and receptor binding.", "mechanism": "ET-1 is a vasoconstrictor secreted by ECs; antagonists reduce pulmonary pressure.", "protein": "Endothelin-1 (ET-1)", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "EDN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P05305" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation modulates VEGFR ligand binding and signaling.", "mechanism": "VEGFR signaling promotes EC proliferation and survival; inhibition induces EC apoptosis and plexiform lesions.", "protein": "VEGFR", "relationship_type": "causal", "source_pmcid": "PMC12689994" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation regulates IL-6R surface expression and ligand binding.", "mechanism": "IL-6R on ECs mediates proinflammatory reverse signaling, driving MCP-1 secretion and monocyte recruitment.", "protein": "IL-6R", "relationship_type": "causal", "source_pmcid": "PMC12689994" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "O-glycosylation critical for thrombomodulin anticoagulant activity.", "mechanism": "Thrombomodulin maintains anticoagulant properties of ECs; dysfunction contributes to thrombosis in PAH.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12689994" }, { "confidence": "high", "disease": "Gynura segetum-induced liver injury", "glycan_involvement": "Degrades mucin O-glycans, altering mucus barrier and gut-liver axis.", "mechanism": "GS increases Akkermansia abundance; associated with liver injury severity.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Mucin O-glycan degradation may increase permeability and inflammation.", "mechanism": "Increased Akkermansia correlates with fibrosis severity, possibly via TLR4 activation.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Mucin O-glycan degradation may exacerbate barrier dysfunction.", "mechanism": "Elevated Akkermansia correlates with inflammation (calprotectin, CRP) in active disease.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Degrade dietary and host glycans, including glycoproteins and mucin.", "mechanism": "Reduced Bifidobacteria in NAFLD; FMT increases Bifidobacteria, associated with reduced inflammation.", "protein": "Bifidobacterium spp. glycosylhydrolases", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Autism spectrum disorder (ASD)", "glycan_involvement": "Degrade complex glycans and glycoproteins, modulating gut environment.", "mechanism": "FMT increases Bifidobacteria, improving GI symptoms in ASD.", "protein": "Bifidobacterium spp. glycosylhydrolases", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Acute liver injury (ALI)", "glycan_involvement": "Ferments carbohydrates and proteins, producing acetate.", "mechanism": "Blautia supplementation reduces liver injury biomarkers and inflammation.", "protein": "Blautia spp.", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Ferment dietary fibers and glycans.", "mechanism": "Decreased in NAFLD; produce SCFAs with anti-inflammatory effects.", "protein": "Ruminococcaceae spp.", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12690191" }, { "confidence": "medium", "disease": "Gynura segetum-induced liver injury", "glycan_involvement": "O-glycosylation critical for mucin barrier function.", "mechanism": "GS-induced Akkermansia expansion leads to mucin degradation, possibly increasing gut permeability and liver injury.", "protein": "Mucin", "relationship_type": "causal (indirect)", "source_pmcid": "PMC12690191" }, { "confidence": "high", "disease": "Hemolysis", "glycan_involvement": "N-glycosylation required for HPX stability and plasma half-life.", "mechanism": "HPX binds extracellular heme, preventing heme-induced oxidative damage and inflammation during hemolysis.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects HPX receptor binding and recycling.", "mechanism": "HPX facilitates recovery from hemolysis-induced anemia by clearing heme and supporting iron homeostasis.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "high", "disease": "Iron overload", "glycan_involvement": "N-glycosylation critical for TfR1 cell surface expression and ligand binding.", "mechanism": "TfR1 mediates iron uptake; dysregulation leads to iron overload, especially in pyruvate kinase deficiency.", "protein": "Transferrin Receptor 1 (TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12690290" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation maintains HPX function in plasma.", "mechanism": "HPX limits heme-driven inflammation and oxidative stress in sepsis.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "high", "disease": "Trauma", "glycan_involvement": "N-glycosylation stabilizes HPX in circulation.", "mechanism": "HPX reduces inflammation and tissue damage following trauma-induced hemolysis.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "N-glycosylation required for HPX transport across blood-brain barrier.", "mechanism": "HPX protects neural tissue from heme toxicity, reducing risk of cognitive impairment.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "medium", "disease": "Pyruvate kinase deficiency", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "Deficiency leads to ineffective erythropoiesis, chronic hemolysis, and iron-loading anemia.", "protein": "Pyruvate kinase", "relationship_type": "causal", "source_pmcid": "PMC12690290" }, { "confidence": "medium", "disease": "Thrombotic conditions", "glycan_involvement": "Glycosylation may regulate exocyst complex assembly.", "mechanism": "Loss impairs platelet granule secretion and receptor trafficking, increasing thrombosis risk.", "protein": "Exocyst complex components 1/3", "relationship_type": "causal", "source_pmcid": "PMC12690290" }, { "confidence": "medium", "disease": "Space anemia", "glycan_involvement": "N-glycosylation required for HPX stability in altered physiological conditions.", "mechanism": "HPX may help maintain iron homeostasis and red cell biology under microgravity, aiding recovery from space anemia.", "protein": "Hemopexin (HPX)", "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "medium", "disease": "Wound healing disorders", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "CD200R1 regulates immune response, reducing scarring and inflammation during wound healing.", "protein": "CD200 Receptor 1", "protein_enriched": { "function": "Inhibitory receptor for the CD200/OX2 cell surface glycoprotein. Limits inflammation by inhibiting the expression of pro-inflammatory molecules including TNF-alpha, interferons, and inducible nitric o", "gene_name": "CD200R1", "glycan_count": 10, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G22573RC", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G00912UN", "G45395BF", "G83646BJ", "G55220VL", "G49108TO" ], "uniprot_id": "Q8TD46" }, "relationship_type": "protective", "source_pmcid": "PMC12690290" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Glycosylation stabilizes tight junction structure.", "mechanism": "Downregulation indicates impaired barrier; JQC restores ZO-1 expression.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation modulates occludin localization/function.", "mechanism": "Reduced occludin correlates with barrier loss; JQC upregulates occludin.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects collagen secretion and ECM deposition.", "mechanism": "Overexpression marks fibrosis; JQC reduces COL1A1.", "protein": "COL1A1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12690457" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may regulate filament assembly.", "mechanism": "Upregulated in activated HSCs; JQC suppresses \u03b1-SMA.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation influences albumin stability.", "mechanism": "Decreased serum albumin reflects liver dysfunction; JQC restores levels.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690457" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation required for EGFR ligand binding.", "mechanism": "EGFR upregulation activates PI3K-AKT pathway; JQC inhibits EGFR.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Elevated IL-6 drives hepatic inflammation; JQC reduces IL-6.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion.", "mechanism": "TNF-\u03b1 promotes liver injury; JQC lowers TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation critical for sIgA transport and function.", "mechanism": "Reduced sIgA impairs mucosal immunity; JQC restores sIgA.", "protein": "sIgA", "relationship_type": "protective", "source_pmcid": "PMC12690457" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may regulate PI3K membrane localization.", "mechanism": "PI3K activation drives fibrosis/inflammation; JQC inhibits PI3K.", "protein": "PI3K (PIK3CA)", "protein_enriched": { "function": "Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:", "gene_name": "PIK3CA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42336" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690457" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "TNF is glycosylated, which affects its stability and receptor binding.", "mechanism": "Promotes inflammation and cartilage degradation via NF-\u03baB and MAPK pathways; targeted by EMS compounds to suppress inflammatory signaling.", "protein": "TNF (Tumor Necrosis Factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "IL-6 glycosylation modulates secretion and receptor interaction.", "mechanism": "Drives inflammatory response and synergizes with TNF and IL-1\u03b2; EMS compounds inhibit IL-6 signaling.", "protein": "IL-6 (Interleukin-6)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "IL1B glycosylation influences its activity and stability.", "mechanism": "Induces chondrocyte apoptosis and matrix degradation; EMS compounds inhibit IL1B-mediated inflammation.", "protein": "IL1B (Interleukin-1 beta)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "AKT1 glycosylation may affect localization and activity.", "mechanism": "Regulates cell survival and inflammation; EMS compounds suppress PI3K-AKT signaling to reduce OA progression.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "TP53 glycosylation can modulate protein stability.", "mechanism": "Controls apoptosis and DNA repair; EMS compounds stabilize TP53 to reduce chondrocyte apoptosis.", "protein": "TP53", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "ESR1 glycosylation affects receptor function.", "mechanism": "Modulates gene expression in response to estrogen; genetic polymorphisms linked to OA susceptibility.", "protein": "ESR1 (Estrogen Receptor Alpha)", "relationship_type": "biomarker", "source_pmcid": "PMC12690495" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "COX-2 glycosylation regulates enzyme activity.", "mechanism": "Enzyme involved in prostaglandin synthesis and inflammation; EMS compounds inhibit PTGS2 to reduce pain and inflammation.", "protein": "PTGS2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "MAPK1 glycosylation may influence signaling efficiency.", "mechanism": "Key kinase in MAPK pathway; EMS compounds inhibit MAPK1 to suppress inflammatory signaling.", "protein": "MAPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "COX-1 glycosylation affects enzyme stability.", "mechanism": "Enzyme involved in prostaglandin synthesis; EMS compounds may modulate PTGS1 to affect inflammation.", "protein": "PTGS1 (COX-1)", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate", "gene_name": "PTGS1", "glycan_count": 7, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G15664MX", "G72747WU", "G46503DX", "G62765YT", "G70101JE", "G80920RR", "G49108TO" ], "uniprot_id": "P23219" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12690495" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "ADRB2 glycosylation modulates receptor trafficking and signaling.", "mechanism": "Regulates cellular responses to catecholamines; implicated in OA pathophysiology.", "protein": "ADRB2 (Beta-2 Adrenergic Receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12690495" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "NS1 is glycosylated, which affects its secretion and immune recognition.", "mechanism": "NS1 is secreted during infection and detected in blood; used for diagnosis.", "protein": "Dengue virus NS1 protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P33478" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "Contains two N-linked glycosylation sites (Asn-67, Asn-153) important for infectivity.", "mechanism": "Envelope protein E mediates viral attachment and entry into host cells.", "protein": "Dengue virus envelope protein E", "relationship_type": "causal", "source_pmcid": "PMC12690620" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "Glycosylation affects IgM structure and detection.", "mechanism": "IgM is produced early in infection and detected by ELISA for diagnosis.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "Glycosylation modulates IgG function and detection.", "mechanism": "IgG is produced later and used for serological diagnosis.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "medium", "disease": "Zika", "glycan_involvement": "N-glycosylation at Asn-153 is critical for viral structure and immune evasion.", "mechanism": "Conserved N-glycosylation site (Asn-153) across flaviviruses, including Zika, used in differential diagnosis.", "protein": "Dengue virus envelope protein E", "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "medium", "disease": "Zika", "glycan_involvement": "Glycosylation patterns influence cross-reactivity.", "mechanism": "NS1 cross-reactivity can cause diagnostic confusion between dengue and Zika.", "protein": "Dengue virus NS1 protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P33478" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "medium", "disease": "Chikungunya", "glycan_involvement": "Glycosylation affects antigenicity and cross-reactivity.", "mechanism": "NS1-based assays may show cross-reactivity, complicating differential diagnosis.", "protein": "Dengue virus NS1 protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P33478" }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "medium", "disease": "Zika", "glycan_involvement": "Glycosylation impacts assay specificity.", "mechanism": "IgM detection used for diagnosis, but cross-reactivity with dengue possible.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "medium", "disease": "Chikungunya", "glycan_involvement": "Glycosylation affects detection and specificity.", "mechanism": "IgG detection used for diagnosis, but cross-reactivity with other arboviruses possible.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "low", "disease": "Yellow fever", "glycan_involvement": "N-glycosylation at Asn-153 modulates immune recognition.", "mechanism": "Conserved glycosylation site (Asn-153) across flaviviruses, including yellow fever, relevant for diagnosis.", "protein": "Dengue virus envelope protein E", "relationship_type": "biomarker", "source_pmcid": "PMC12690620" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "PSMA is a glycoprotein; glycosylation is required for proper folding and cell surface expression, enabling ligand binding.", "mechanism": "PSMA is markedly overexpressed in prostate adenocarcinoma compared to benign tissue; its extracellular domain is accessible for imaging and targeting.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Glycosylation maintains PSMA's cell surface localization and ligand accessibility.", "mechanism": "PSMA-targeted radioligand therapies (e.g., 177Lu-PSMA-617, 225Ac-PSMA-617) selectively deliver cytotoxic radiation to PSMA-positive tumor cells.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "High-grade prostate cancer", "glycan_involvement": "Glycosylation status may influence PSMA stability and expression levels.", "mechanism": "PSMA expression increases with higher Gleason score and advanced disease stage, correlating with tumor aggressiveness.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "medium", "disease": "Neuroendocrine prostate cancer", "glycan_involvement": "Altered glycosylation may contribute to loss of cell surface PSMA in lineage plasticity.", "mechanism": "Loss or reduction of PSMA expression in neuroendocrine differentiation leads to resistance to PSMA-targeted therapies.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Glycosylation affects antibody binding and internalization efficiency.", "mechanism": "PSMA antibody-drug conjugates (ADCs) target PSMA for delivery of cytotoxic agents.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "Glycosylation supports PSMA's functional conformation for ligand binding.", "mechanism": "Intensity of intraprostatic PSMA uptake (SUVmax) on PET imaging correlates with tumor grade and risk of recurrence.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Glycosylation ensures PSMA cell surface targeting for ligand-conjugated therapeutics.", "mechanism": "PSMA-targeted delivery of microRNA (miR-34a) for experimental RNA therapy in PSMA-positive tumors.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "Glycosylation is necessary for PSMA's extracellular domain presentation.", "mechanism": "PSMA PET imaging is used for staging, restaging, and detection of biochemical recurrence.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "Prostate adenocarcinoma", "glycan_involvement": "Glycosylation may affect heterogeneity of PSMA expression.", "mechanism": "PSMA-targeted radioligand therapy efficacy depends on uniform PSMA expression across tumor sites.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691006" }, { "confidence": "medium", "disease": "Prostate adenocarcinoma", "glycan_involvement": "Glycosylation may modulate PSMA stability under different signaling conditions.", "mechanism": "PSMA expression is upregulated by androgen deprivation and downregulated in AR-independent tumor evolution.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691006" }, { "confidence": "high", "disease": "Anaplastic Thyroid Cancer", "glycan_involvement": "Glycosylation of VSV-G is required for proper folding and function in viral particle assembly.", "mechanism": "Used as a component in lentiviral packaging for CRISPRi-mediated gene repression studies.", "protein": "VSV-G envelope glycoprotein", "relationship_type": "experimental tool", "source_pmcid": "PMC12691012" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "AGP is heavily N-glycosylated; glycosylation modulates its immunomodulatory function.", "mechanism": "AGP levels reflect innate immune activation and acute phase response in broilers.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "medium", "disease": "Nutritional deficiency-induced immune dysregulation", "glycan_involvement": "Altered glycosylation may affect AGP's anti-inflammatory properties.", "mechanism": "AGP levels increase in response to nutrient deficiency, indicating immune stress.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation status may influence AGP's anti-inflammatory activity.", "mechanism": "S. boulardii supplementation lowers AGP in nutrient-deficient diets, suggesting anti-inflammatory effects.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "protective", "source_pmcid": "PMC12691015" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "IFN-\u03b3 is glycosylated, which may affect its stability and receptor interactions.", "mechanism": "IFN-\u03b3 is a key cytokine in Th1-type immune responses and inflammation.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "medium", "disease": "Nutritional deficiency-induced immune dysregulation", "glycan_involvement": "Glycosylation may modulate IFN-\u03b3's immunoregulatory function.", "mechanism": "S. boulardii supplementation lowers IFN-\u03b3 in nutrient-deficient diets, indicating mitigation of excessive innate immune activation.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12691015" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "IgA is O- and N-glycosylated, essential for mucosal protection.", "mechanism": "Jejunal sIgA levels indicate mucosal immune status and barrier function.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "medium", "disease": "Nutritional deficiency-induced immune dysregulation", "glycan_involvement": "IgM glycosylation affects its stability and immune function.", "mechanism": "Serum IgM levels decrease with nutrient restriction, reflecting impaired humoral immunity.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "low", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may modulate AGP's antioxidant properties.", "mechanism": "AGP elevation is associated with increased oxidative stress in nutrient-deficient states.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691015" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation may affect IFN-\u03b3's activity and therapeutic potential.", "mechanism": "Modulation of IFN-\u03b3 by S. boulardii suggests potential for controlling inflammation.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691015" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation is critical for AGP's function in inflammation.", "mechanism": "AGP is directly involved in the acute phase response during inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "causal", "source_pmcid": "PMC12691015" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Chondroitin sulfate chains mediate ECM interactions and MMP activation, facilitating invasion.", "mechanism": "Overexpression promotes proliferation, survival, migration, and chemoresistance; targeting CSPG4 impairs malignant behavior and enhances chemotherapy sensitivity.", "protein": "CSPG4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691020" }, { "confidence": "high", "disease": "Metastatic Osteosarcoma", "glycan_involvement": "CS chains enable binding to pro-MMP-2, promoting ECM degradation and metastasis.", "mechanism": "High CSPG4 correlates with increased metastasis and shorter survival; vaccine targeting reduces lung metastases in models.", "protein": "CSPG4", "relationship_type": "biomarker", "source_pmcid": "PMC12691020" }, { "confidence": "medium", "disease": "Angiogenic Osteosarcoma", "glycan_involvement": "CS glycosylation facilitates growth factor binding and vascular remodeling.", "mechanism": "CSPG4 supports angiogenesis by acting as co-receptor for FGF-2/PDGF and recruiting pericytes.", "protein": "CSPG4", "relationship_type": "causal", "source_pmcid": "PMC12691020" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation status not detailed; functional as a glycoprotein antiporter.", "mechanism": "xCT maintains redox balance, resists ferroptosis, and confers chemoresistance; inhibition sensitizes cells to therapy.", "protein": "xCT (SLC7A11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691020" }, { "confidence": "high", "disease": "Metastatic Osteosarcoma", "glycan_involvement": "Glycoprotein structure may affect membrane localization and function.", "mechanism": "High xCT expression correlates with increased invasion, migration, and poor prognosis.", "protein": "xCT (SLC7A11)", "relationship_type": "biomarker", "source_pmcid": "PMC12691020" }, { "confidence": "high", "disease": "Chemoresistant Osteosarcoma", "glycan_involvement": "Glycosylation required for proper folding and cell surface expression.", "mechanism": "TLR2 activation by HMGB1 promotes NF-\u03baB signaling, CSC self-renewal, and chemoresistance; inhibition enhances chemotherapy efficacy.", "protein": "TLR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691020" }, { "confidence": "medium", "disease": "Metastatic Osteosarcoma", "glycan_involvement": "Glycosylation status not specified; functional as a glycoprotein receptor.", "mechanism": "TLR2 activation increases migration, invasion, and EMT via NF-\u03baB and PI3K/AKT pathways.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC12691020" }, { "confidence": "medium", "disease": "Angiogenic Osteosarcoma", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "TLR2 activation in endothelial cells promotes angiogenesis via DAMP-induced signaling, independently of VEGF.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC12691020" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "N-glycosylation required for ligand binding and receptor activation.", "mechanism": "Overexpressed in OSA; CSPG4 potentiates PDGFR\u03b1 signaling, promoting proliferation and angiogenesis.", "protein": "PDGFR\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12691020" }, { "confidence": "low", "disease": "Osteosarcoma", "glycan_involvement": "O-glycosylation of MUC1 modulates cell adhesion and immune evasion.", "mechanism": "Interacts with xCT in cancer stem cells, supporting stemness and therapy resistance.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691020" }, { "confidence": "high", "disease": "Pleural Mesothelioma", "glycan_involvement": "Mesothelin is a glycoprotein; glycosylation may affect stability and immune recognition.", "mechanism": "Overexpressed on mesothelial cells; enhances cellular adhesion and local invasion; targeted by antibodies, ADCs, CAR-T, TRuC therapies.", "protein": "Mesothelin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691059" }, { "confidence": "high", "disease": "Pleural Mesothelioma", "glycan_involvement": "Derived from glycoprotein mesothelin; glycosylation status not specified.", "mechanism": "Cleaved mesothelin fragment in serum/pleural fluid; FDA-approved for treatment monitoring.", "protein": "Soluble Mesothelin-Related Protein (SMRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation may regulate secretion and ECM interactions.", "mechanism": "Secreted glycoprotein; promotes tumor growth via PI3K/AKT pathway, cellular adhesion, motility, invasion.", "protein": "Fibulin-3", "protein_enriched": { "function": "Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulato", "gene_name": "EFEMP1", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27391WQ", "G43417UB", "G53434XO", "G57317CE", "G29068FM", "G57321FI", "G71142DF", "G49108TO" ], "uniprot_id": "Q12805" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation may affect cell adhesion properties.", "mechanism": "Cell-adhesion glycoprotein; elevated in pleural fluid in PM.", "protein": "CD157", "protein_enriched": { "function": "Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly (PubMed:20002496, PubMed:21211722, PubMed:26841755). Also participates in several important DNA repair mech", "gene_name": "NAP1L1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55209" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Sialylated O-glycans critical for function.", "mechanism": "Induces platelet aggregation, promotes tumor immune evasion and dissemination; highly specific for PM in vitro.", "protein": "Podoplanin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Heavily O-glycosylated mucin; glycosylation affects detection and function.", "mechanism": "Elevated in serum/pleural fluid in PM; correlates with SMRP and prognosis.", "protein": "KL-6 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Derived from glycoprotein precursor; glycosylation status not specified.", "mechanism": "Cleavage product of mesothelin precursor; elevated in pleural fluid in PM.", "protein": "Megakaryocyte Potentiating Factor (MPF)", "protein_enriched": { "function": "", "gene_name": "MSLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13421-2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "low", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation may affect secretion and immune modulation.", "mechanism": "Combined with SMRP improves diagnostic sensitivity/specificity.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated in serum/pleural fluid in PM; associated with poor prognosis.", "protein": "Calretinin", "protein_enriched": { "function": "Calcium-binding protein involved in calcium homeostasis and signal transduction. It plays a critical role in buffering intracellular calcium levels and modulating calcium-dependent signaling pathways ", "gene_name": "CALB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22676" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated in pleural fluid; part of diagnostic signature with methylation markers.", "protein": "Cytokeratin 19 fragment (CYFRA 21-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691059" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Heparan sulfate glycosylation critical for GPC3 function and tumor cell recognition.", "mechanism": "GPC3 is overexpressed in HCC and targeted by CAR-T cells and biomimetic nanoparticles for tumor-specific therapy.", "protein": "Glypican-3 (GPC3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia", "glycan_involvement": "CD19 is a glycoprotein; glycosylation may affect antigenicity and CAR binding.", "mechanism": "CD19 is expressed on B-cells; anti-CD19 CAR-T cells and CAR-exosomes target and lyse malignant cells.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "high", "disease": "Non-small cell lung cancer", "glycan_involvement": "EGFR glycosylation modulates ligand binding and immune recognition.", "mechanism": "EGFR is overexpressed in NSCLC; anti-EGFR CAR-exosomes deliver cytotoxic agents and mediate tumor cell killing.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "medium", "disease": "Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)", "glycan_involvement": "Glycosylation of CAR and CD19 may influence EV interactions.", "mechanism": "CAR+ EVs bearing CD19 CAR correlate with ICANS onset and severity; may interact with CD19+ cells in the CNS.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691105" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "CD3 glycosylation may affect exosome binding and T-cell activation.", "mechanism": "Exosomes functionalized with anti-CD3 scFv enhance T-cell targeting and activation against solid tumors.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "medium", "disease": "Hematological malignancies", "glycan_involvement": "Integrin glycosylation modulates cell adhesion and targeting.", "mechanism": "Exosome integrin profile (e.g., LFA-1) enables selective targeting of T cells for gene delivery in cancer therapy.", "protein": "LFA-1 (Integrin \u03b1L\u03b22)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation affects immunogenicity.", "mechanism": "HBsAg-based VLPs used as vaccines and potential ex vivo gene delivery vehicles.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "therapeutic_target/vaccine", "source_pmcid": "PMC12691105" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "PD-1 glycosylation may regulate receptor stability and immune checkpoint function.", "mechanism": "CRISPR/Cas knockout of PD-1 in CAR-T cells enhances anti-tumor response by preventing PD-L1 mediated suppression.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691105" }, { "confidence": "medium", "disease": "Cytokine Release Syndrome (CRS)", "glycan_involvement": "CD28 glycosylation may modulate receptor signaling.", "mechanism": "CD28 co-stimulatory domain in CARs can drive potent T-cell activation, increasing CRS risk.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC12691105" }, { "confidence": "high", "disease": "Solid tumors", "glycan_involvement": "Heparan sulfate chains are essential for GPC3's tumor-specific expression.", "mechanism": "GPC3 expression distinguishes tumor from normal tissue, enabling targeted therapy.", "protein": "Glypican-3 (GPC3)", "relationship_type": "biomarker", "source_pmcid": "PMC12691105" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation affects apoB structure and interaction with arterial glycosaminoglycans.", "mechanism": "Directly quantifies atherogenic particle number; higher levels predict CAD presence and severity.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylated domains mediate binding to arterial glycosaminoglycans.", "mechanism": "Elevated apoB particles retained in arterial intima via electrostatic interactions, initiating plaque formation.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "causal", "source_pmcid": "PMC12691110" }, { "confidence": "high", "disease": "Left main coronary artery disease", "glycan_involvement": "Glycosylation may influence apoB retention and receptor interactions.", "mechanism": "ApoB is the only lipid biomarker independently associated with left main disease.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "medium", "disease": "Three vessel coronary disease", "glycan_involvement": "Glycosylation may affect particle clearance and atherogenicity.", "mechanism": "ApoB independently predicts three vessel disease after adjustment for risk factors.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "medium", "disease": "Plaque vulnerability", "glycan_involvement": "Glycosylation may modulate apoB's role in plaque stability.", "mechanism": "Lower apoB levels (<65 mg/dL) are linked to decreased plaque vulnerability.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Lp(a) is heavily glycosylated, affecting its atherogenic properties.", "mechanism": "Lp(a) is an apoB-containing lipoprotein contributing to atherogenic particle burden.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12691110" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "LDL glycosylation influences receptor binding and clearance.", "mechanism": "LDL-C is a traditional biomarker but less predictive than apoB for CAD severity.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation may affect apoB's response to lipid-lowering therapies.", "mechanism": "Lowering apoB is recommended as a treatment goal in guidelines for high-risk patients.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691110" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation may influence discordance and risk prediction.", "mechanism": "Residual apoB (discordantly high apoB relative to LDL-C) remains associated with CAD risk.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "low", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Indirect; glycosylation may affect apoB's role in atherogenesis and subsequent AF risk.", "mechanism": "CAD (including non-significant atherosclerosis) is associated with higher AF prevalence; apoB tracks CAD burden.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12691110" }, { "confidence": "high", "disease": "Drug-resistant breast cancer", "glycan_involvement": "N-glycosylation critical for membrane localization and function.", "mechanism": "Pgp overexpression leads to ATP-dependent drug efflux, conferring resistance; Akt inhibitors sensitize Pgp-overexpressing cells.", "protein": "P-glycoprotein (Pgp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691131" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation may affect stability and DNA repair activity.", "mechanism": "BRCA1 mutation impairs homologous recombination, increasing sensitivity to PARP inhibitors.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "causal", "source_pmcid": "PMC12691131" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Potential glycosylation modulates protein interactions.", "mechanism": "BRCA2 mutation leads to defective DNA repair, making cells susceptible to PARP inhibition.", "protein": "BRCA2", "protein_enriched": { "function": "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by ", "gene_name": "BRCA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G03238UC", "G37399XV", "G41247ZX", "G90382BL", "G49108TO" ], "uniprot_id": "P51587" }, "relationship_type": "causal", "source_pmcid": "PMC12691131" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate Akt membrane localization.", "mechanism": "Aberrant Akt activation promotes survival, metabolism, and resistance; inhibition disrupts these processes.", "protein": "Akt (Protein Kinase B)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691131" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect nuclear localization and activity.", "mechanism": "PARP-1 repairs DNA damage; inhibition induces synthetic lethality in BRCA-mutant cells.", "protein": "PARP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691131" }, { "confidence": "medium", "disease": "Chemotherapy resistance", "glycan_involvement": "O-glycosylation modulates stability and transcriptional activity.", "mechanism": "HIF-1\u03b1 upregulates glycolytic enzymes and glucose transporters, promoting metabolic adaptation and resistance.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12691131" }, { "confidence": "medium", "disease": "Apoptosis resistance", "glycan_involvement": "Glycosylation may affect anti-apoptotic function.", "mechanism": "Survivin inhibits apoptosis; Akt inhibition reduces survivin expression.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691131" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation may influence mitochondrial localization.", "mechanism": "Release of cytochrome c from mitochondria triggers apoptosis; combination therapy promotes release.", "protein": "Cytochrome c", "protein_enriched": { "function": "Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers ", "gene_name": "CYCS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P99999" }, "relationship_type": "causal", "source_pmcid": "PMC12691131" }, { "confidence": "low", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may modulate mitochondrial targeting.", "mechanism": "IF1 regulates mitochondrial ATP synthase, influencing redox balance and cell survival.", "protein": "ATPase inhibitory factor 1 (IF1)", "protein_enriched": { "function": "Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out o", "gene_name": "ATP5IF1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UII2" }, "relationship_type": "protective", "source_pmcid": "PMC12691131" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation essential for membrane trafficking and glucose uptake.", "mechanism": "GLUT upregulation supports glycolytic metabolism in cancer cells; HIF-1\u03b1 regulates GLUT expression.", "protein": "Glucose transporter (GLUT)", "relationship_type": "biomarker", "source_pmcid": "PMC12691131" }, { "confidence": "high", "disease": "Fatty liver disease", "glycan_involvement": "VLDL assembly and secretion depend on glycosylated apolipoproteins.", "mechanism": "Increased VLDL secretion promotes hepatic triglyceride export, reducing lipid accumulation in the liver.", "protein": "Very-low-density lipoprotein (VLDL)", "relationship_type": "protective", "source_pmcid": "PMC12691157" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "N-glycosylation is essential for ApoB100 folding and VLDL secretion.", "mechanism": "Upregulation of ApoB100 expression enhances VLDL assembly and export, preventing hepatic triglyceride accumulation.", "protein": "Apolipoprotein B100", "relationship_type": "protective", "source_pmcid": "PMC12691157" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "N-glycosylation required for MTTP function.", "mechanism": "MTTP facilitates VLDL assembly; increased activity promotes lipid export from liver.", "protein": "Microsomal triglyceride transfer protein (MTTP)", "relationship_type": "protective", "source_pmcid": "PMC12691157" }, { "confidence": "medium", "disease": "Reduced milk production", "glycan_involvement": "O-glycosylation of casein affects its stability and function in milk.", "mechanism": "Increased casein gene expression (and thus casein glycoprotein synthesis) improves milk yield and quality.", "protein": "Casein", "relationship_type": "causal", "source_pmcid": "PMC12691157" }, { "confidence": "low", "disease": "Protein-energy malnutrition", "glycan_involvement": "Glycosylation modulates plasma half-life and function.", "mechanism": "Decreased blood histidine reflects tissue protein mobilization during negative energy balance.", "protein": "Histidine-rich glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12691157" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation affects stability and transport function.", "mechanism": "Serum albumin levels reflect hepatic synthetic function; altered in metabolic stress.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691157" }, { "confidence": "low", "disease": "Impaired immune function", "glycan_involvement": "Fc N-glycosylation modulates effector function.", "mechanism": "Altered glycosylation of IgG can modulate immune responses; not directly measured but inferred from immune pathway enrichment.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691157" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Bacterial glycoproteins degrade host and dietary glycans.", "mechanism": "Enrichment of Muribaculaceae improves fiber fermentation and VFA production, supporting metabolic health.", "protein": "Muribaculaceae glycoside hydrolases", "relationship_type": "protective", "source_pmcid": "PMC12691157" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Bacterial glycoproteins mediate host-microbe interactions.", "mechanism": "Bifidobacterium enrichment supports gut barrier and immune function.", "protein": "Bifidobacterium exopolysaccharide-associated proteins", "relationship_type": "protective", "source_pmcid": "PMC12691157" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "N-glycosylation modulates iron transport and immune signaling.", "mechanism": "Altered transferrin glycosylation is associated with inflammation and metabolic stress.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691157" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Surface presentation and shedding may involve glycan interactions (e.g., binding to globotriaosylceramide, phosphatidylserine).", "mechanism": "Induced hyperthermia upregulates and releases HSP70, acting as a danger signal to activate immune cells and enhance antigen presentation.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect extracellular release and immune recognition.", "mechanism": "Hyperthermia-induced HSP90 release activates dendritic cells and macrophages, promoting proinflammatory cytokine release and immune activation.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691179" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "ER-resident glycoprotein; glycosylation required for proper folding and antigen presentation.", "mechanism": "gp96 presentation by APCs is increased by hyperthermia, enhancing cross-presentation of tumor antigens to T cells.", "protein": "gp96 (HSP90B1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Tumor Immune Evasion", "glycan_involvement": "N-glycosylation critical for MHC-I stability and antigen presentation.", "mechanism": "Hyperthermia upregulates MHC-I affinity and expression, improving CTL recognition of tumor cells.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for MHC-II trafficking and function.", "mechanism": "Hyperthermia enhances MHC-II expression and antigen presentation, boosting adaptive immune responses.", "protein": "MHC-II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Tumor Inflammation", "glycan_involvement": "N-glycosylation modulates ICAM-1 binding to integrins.", "mechanism": "Hyperthermia upregulates ICAM-1, facilitating immune cell adhesion and trafficking into tumors.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691179" }, { "confidence": "medium", "disease": "Tumor Metastasis", "glycan_involvement": "Glycosylation required for selectin-mediated cell adhesion.", "mechanism": "Hyperthermia-induced IL-6 upregulates E-selectin, promoting lymphocyte trafficking and potentially influencing metastasis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12691179" }, { "confidence": "medium", "disease": "Tumor Angiogenesis", "glycan_involvement": "Glycosylation essential for ligand binding.", "mechanism": "Hyperthermia increases P-selectin expression, enhancing immune cell recruitment and vascular interactions.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691179" }, { "confidence": "medium", "disease": "Tumor Metastasis", "glycan_involvement": "Glycosylation modulates selectin-ligand interactions.", "mechanism": "Hyperthermia upregulates L-selectin, facilitating lymphocyte homing to tumor sites.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects MICA stability and surface expression.", "mechanism": "Hyperthermia upregulates MICA, enhancing NK cell activation via NKG2D receptor.", "protein": "MICA", "protein_enriched": { "function": "Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and ", "gene_name": "MICA", "glycan_count": 7, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G64527OM", "G80920RR", "G10773YW", "G41247ZX", "G70441OD", "G08290VR" ], "uniprot_id": "Q29983" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691179" }, { "confidence": "high", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "Likely N-glycosylated, affecting secretion and stability.", "mechanism": "Highly upregulated in plasma of metastatic PC, especially with liver metastasis; involved in tumor immune cell infiltration.", "protein": "ADH1C", "protein_enriched": { "function": "Alcohol dehydrogenase. Exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism", "gene_name": "ADH1C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00326" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "high", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "Likely N-glycosylated, influencing plasma detection.", "mechanism": "Highly upregulated in plasma of metastatic PC, especially with liver metastasis; associated with increased risk in other cancers.", "protein": "ADH1B", "protein_enriched": { "function": "Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitr", "gene_name": "ADH1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00325" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "high", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "N-glycosylation may affect mitochondrial targeting and function.", "mechanism": "Upregulated in metastatic PC; urea cycle enzyme, knockdown reduces cell viability.", "protein": "CPS1", "protein_enriched": { "function": "Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell", "gene_name": "CPS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G70223PD", "G95865ZB", "G59324HL", "G80920RR", "G49108TO" ], "uniprot_id": "P31327" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "N-glycosylation modulates hormone binding and plasma half-life.", "mechanism": "Elevated in metastatic PC plasma; binds sex hormones.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "N-glycosylation critical for cell surface localization.", "mechanism": "Cell surface protein, elevated in metastatic PC; involved in adenosine generation and immune modulation.", "protein": "NT5E", "protein_enriched": { "function": "Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate (PubMed:21933152, PubMed:22997138, PubMed:", "gene_name": "NT5E", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G08290VR", "G17208MA", "G43223CG", "G62765YT", "G70441OD", "G84862VB", "G90659AW", "G00912UN", "G04657PL", "G07246CJ", "G08918WF", "G14972EH", "G27058EU", "G35541EV", "G41071NU", "G45395BF", "G57776ZS", "G65184UU", "G70232NH", "G79666IR", "G83646BJ", "G86880BF", "G87661QW", "G80075MS", "G49108TO" ], "uniprot_id": "P21589" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "N-glycosylation affects secretion and function.", "mechanism": "Secreted glycoprotein, elevated in metastatic PC; modulates angiogenesis.", "protein": "LRG1", "protein_enriched": { "function": "Probable Na(+)/H(+) antiporter", "gene_name": "TMCO3", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G43417UB", "G07246CJ", "G62765YT", "G84225JN", "G57321FI", "G19973ZD", "G49108TO" ], "uniprot_id": "Q6UWJ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "O-glycosylation may regulate activity.", "mechanism": "Secreted growth factor, elevated in metastatic PC; promotes cell proliferation.", "protein": "MDK", "protein_enriched": { "function": "Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:2", "gene_name": "MTR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99707" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "Potential O-glycosylation modulates function.", "mechanism": "Elevated in metastatic PC; involved in peptide chain elongation.", "protein": "EEF2", "protein_enriched": { "function": "Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-transloc", "gene_name": "EEF2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P13639" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "N-glycosylation may affect stability.", "mechanism": "Elevated in metastatic PC; glycolytic enzyme.", "protein": "PKLR", "protein_enriched": { "function": "Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis", "gene_name": "PKLR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30613" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "medium", "disease": "Pancreatic Cancer (Metastatic)", "glycan_involvement": "Potential O-glycosylation, role in ribosome assembly.", "mechanism": "Ribosomal protein, elevated in metastatic PC; reflects increased ribosome biogenesis.", "protein": "RPL13A", "protein_enriched": { "function": "", "gene_name": "sgta-prov", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6P2W1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691180" }, { "confidence": "high", "disease": "Kidney transplantation", "glycan_involvement": "N-glycosylation affects albumin stability and half-life.", "mechanism": "Serum albumin levels reflect patient metabolic status and influence tacrolimus clearance.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Kidney transplantation", "glycan_involvement": "Highly glycosylated; glycan structure modulates binding affinity.", "mechanism": "Tacrolimus binds to alpha-1-acid glycoprotein, affecting its pharmacokinetics.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Nephrotoxicity", "glycan_involvement": "Altered glycosylation may affect albumin clearance.", "mechanism": "Low albumin is associated with increased tacrolimus concentration and nephrotoxicity risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Graft rejection", "glycan_involvement": "Potential O-glycosylation may affect protein stability.", "mechanism": "FKBP12 binds tacrolimus, inhibiting calcineurin and T-cell activation, preventing rejection.", "protein": "Tacrolimus-binding protein (FKBP12)", "protein_enriched": { "function": "Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents th", "gene_name": "FKBP1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62942" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "N-glycosylation modulates CRP function and clearance.", "mechanism": "CRP is elevated during infection and inflammation post-transplant.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Graft rejection", "glycan_involvement": "Fc N-glycosylation modulates effector function.", "mechanism": "IgG levels reflect immune activation and risk of rejection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation pattern changes in liver disease.", "mechanism": "Altered transferrin glycoforms indicate hepatic dysfunction, which affects tacrolimus metabolism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects clearance and function.", "mechanism": "Haptoglobin levels reflect hemolysis and anemia risk post-transplant.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Ceruloplasmin is decreased in liver dysfunction, impacting oxidative stress.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "low", "disease": "Chronic kidney disease", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "LDL receptor glycosylation status may be altered in CKD, affecting lipid metabolism.", "protein": "LDL receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12691189" }, { "confidence": "high", "disease": "Impaired Immune Function", "glycan_involvement": "Globulin glycosylation affects immune recognition and stability.", "mechanism": "Elevated globulin indicates improved immune status; GAA and 5,6-DMB + Co increase globulin.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Impaired Immune Function", "glycan_involvement": "Albumin glycosylation modulates half-life and function.", "mechanism": "Albumin levels reflect protein status and immune health; modulated by dietary additives.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "AST glycosylation may affect enzyme stability and activity.", "mechanism": "Positive association of Prevotella with AST suggests microbial modulation of liver function.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "ALT glycosylation impacts enzyme secretion and turnover.", "mechanism": "Fretibacterium positively correlates with ALT, indicating microbial influence on liver enzymes.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL particles contain glycoproteins (ApoB) affecting receptor binding.", "mechanism": "AGF increases LDL-CH; Quinella negatively correlates with LDL-CH, indicating microbial regulation of lipid metabolism.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-CH)", "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "high", "disease": "Impaired Nitrogen Utilization", "glycan_involvement": "Serum TP includes glycoproteins; glycosylation affects solubility and function.", "mechanism": "Rikenellaceae_RC9_gut_group positively correlates with TP, indicating improved protein metabolism with 5,6-DMB + Co.", "protein": "Total Protein (TP)", "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Impaired Nitrogen Utilization", "glycan_involvement": "Glycosylation enhances globulin stability and immune interactions.", "mechanism": "GAA and 5,6-DMB + Co increase globulin, supporting nitrogen retention and immune function.", "protein": "Globulin", "relationship_type": "protective", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Impaired Nitrogen Utilization", "glycan_involvement": "Glycosylation affects albumin\u2019s transport and antioxidant properties.", "mechanism": "Albumin reflects overall protein status; modulated by dietary additives.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "ApoB glycosylation on LDL modulates receptor interactions.", "mechanism": "AGF supplementation increases LDL-CH, possibly via microbial shifts affecting lipid metabolism.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-CH)", "relationship_type": "causal", "source_pmcid": "PMC12691208" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation status influences globulin secretion and function.", "mechanism": "Globulin levels reflect hepatic synthetic function; increased by GAA and 5,6-DMB + Co.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691208" }, { "confidence": "high", "disease": "B-cell non-Hodgkin lymphoma", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "CD20 is targeted by rituximab for B-cell depletion in lymphoma therapy.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691211" }, { "confidence": "high", "disease": "Autoimmune diseases (e.g., rheumatoid arthritis, systemic sclerosis, ANCA-associated vasculitis, pemphigus vulgaris, neuromyelitis optica)", "glycan_involvement": "CD20 glycosylation may influence antibody recognition.", "mechanism": "CD20+ B cells are depleted by rituximab to modulate autoimmune responses.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691211" }, { "confidence": "high", "disease": "Rituximab-induced interstitial lung disease (R-ILD)", "glycan_involvement": "Fc glycosylation of rituximab modulates effector functions (ADCC/CDC), possibly influencing toxicity.", "mechanism": "Rituximab administration can trigger immune-mediated lung injury (R-ILD).", "protein": "Rituximab", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "medium", "disease": "Interstitial pneumonitis", "glycan_involvement": "Fc glycosylation affects immune activation and toxicity.", "mechanism": "Rituximab can cause interstitial pneumonitis as a pulmonary adverse event.", "protein": "Rituximab", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Not directly addressed; possible role via immune modulation.", "mechanism": "Chronic or severe R-ILD may progress to pulmonary fibrosis.", "protein": "Rituximab", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "medium", "disease": "Alveolar hemorrhage", "glycan_involvement": "Not specified.", "mechanism": "Severe R-ILD can manifest as alveolar hemorrhage.", "protein": "Rituximab", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "medium", "disease": "Rituximab-induced interstitial lung disease (R-ILD)", "glycan_involvement": "Fc glycosylation critical for Fc\u03b3RIII binding and ADCC.", "mechanism": "Fc region of rituximab binds Fc\u03b3RIII on NK cells, triggering ADCC and possible lung injury.", "protein": "Fc\u03b3RIII (CD16)", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "medium", "disease": "Opportunistic pneumonitis (e.g., Pneumocystis jirovecii)", "glycan_involvement": "Not specified.", "mechanism": "Rituximab-induced immunosuppression increases risk of opportunistic lung infections.", "protein": "Rituximab", "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "low", "disease": "Rituximab-induced interstitial lung disease (R-ILD)", "glycan_involvement": "CD20 glycosylation may affect immune recognition.", "mechanism": "CD20 targeting by rituximab may trigger immune-mediated lung injury.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC12691211" }, { "confidence": "high", "disease": "B-cell non-Hodgkin lymphoma", "glycan_involvement": "Fc glycosylation enhances immune effector function.", "mechanism": "Rituximab is used to treat B-cell NHL via CD20 targeting.", "protein": "Rituximab", "relationship_type": "therapeutic", "source_pmcid": "PMC12691211" }, { "confidence": "high", "disease": "Chemotherapy-induced anemia", "glycan_involvement": "Bacterial glycoproteins may modulate immune signaling via glycan motifs.", "mechanism": "Enrichment of Eubacteriaceae associated with increased risk of anemia, possibly via pro-inflammatory cytokine production.", "protein": "Eubacteriaceae glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced anemia", "glycan_involvement": "LPS and glycoprotein structures may trigger host immune response.", "mechanism": "Enrichment linked to anemia, likely through inflammation and hepcidin-mediated iron sequestration.", "protein": "Enterobacteriaceae glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12691247" }, { "confidence": "high", "disease": "Chemotherapy-induced neutropenia", "glycan_involvement": "Glycoproteins may influence SCFA production and immune modulation.", "mechanism": "Depletion associated with severe neutropenia; butyrate production supports hematopoiesis.", "protein": "Eubacterium hallii group glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "high", "disease": "Chemotherapy-induced thrombocytopenia", "glycan_involvement": "Glycoprotein-mediated host-microbe interactions.", "mechanism": "Severe depletion linked to thrombocytopenia; may affect platelet production via microbial metabolites.", "protein": "Eubacterium limosum glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced hepatotoxicity (ALT elevation)", "glycan_involvement": "Bacterial glycoproteins may interact with hepatic immune cells.", "mechanism": "Depletion associated with ALT elevation; may play a role in maintaining liver homeostasis.", "protein": "Burkholderia-Caballeronia-Paraburkholderia glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced hepatotoxicity (AST elevation)", "glycan_involvement": "Mucin-degrading glycoproteins modulate host-microbe interface.", "mechanism": "Depletion linked to AST elevation; Akkermansia supports gut barrier and liver health.", "protein": "Akkermansiaceae glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "high", "disease": "Chemotherapy-induced hand-foot syndrome", "glycan_involvement": "Glycoproteins involved in SCFA production and epithelial signaling.", "mechanism": "Depletion associated with hand-foot syndrome; butyrate producers support epithelial integrity.", "protein": "Lachnospiraceae glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced hand-foot syndrome", "glycan_involvement": "Glycoprotein-mediated SCFA production.", "mechanism": "Depletion linked to syndrome; Roseburia produces butyrate, supporting anti-inflammatory effects.", "protein": "Roseburia glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced hand-foot syndrome", "glycan_involvement": "Glycoproteins involved in butyrate synthesis.", "mechanism": "Depletion associated with syndrome; butyrate production may protect against epithelial toxicity.", "protein": "Butyricicoccus glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "medium", "disease": "Chemotherapy-induced diarrhea", "glycan_involvement": "Glycoproteins may modulate mucosal immunity.", "mechanism": "Depletion associated with diarrhea; Christensenella supports gut barrier function.", "protein": "Christensenella glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12691247" }, { "confidence": "high", "disease": "MGUS", "glycan_involvement": "Immunoglobulins are heavily glycosylated, affecting stability and immune recognition.", "mechanism": "Serum monoclonal immunoglobulin is diagnostic for MGUS.", "protein": "Immunoglobulin (M-protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation modulates immunoglobulin function and half-life.", "mechanism": "Elevated MGUS prevalence in prostate cancer patients suggests shared inflammatory or immune pathways.", "protein": "Immunoglobulin (M-protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "N-glycosylation critical for alpha-2-macroglobulin function and clearance.", "mechanism": "Elevated alpha-2-globulin fraction (includes alpha-2-macroglobulin) in prostate cancer reflects systemic inflammation.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "Glycosylation affects ceruloplasmin stability and activity.", "mechanism": "Ceruloplasmin is an acute-phase reactant elevated in inflammatory states.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "Glycosylation modulates haptoglobin\u2019s hemoglobin-binding and clearance.", "mechanism": "Haptoglobin is increased in inflammation and certain anemias.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "MGUS", "glycan_involvement": "N-glycosylation influences fibrinogen\u2019s clotting and inflammatory properties.", "mechanism": "Elevated fibrinogen levels are associated with MGUS presence, reflecting systemic inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "MGUS", "glycan_involvement": "Heparan sulfate glycosylation is essential for CD138\u2019s cell adhesion and signaling.", "mechanism": "CD138 marks plasma cells; increased infiltration in MGUS patients suggests plasma cell expansion.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "high", "disease": "MGUS", "glycan_involvement": "Light chains are glycosylated, affecting aggregation and renal clearance.", "mechanism": "Abnormal free light chain ratio is diagnostic for MGUS.", "protein": "Free Light Chains (kappa/lambda)", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Altered glycosylation patterns of PSA are linked to cancer aggressiveness.", "mechanism": "Elevated PSA is used for prostate cancer detection.", "protein": "Prostate-Specific Antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "medium", "disease": "Chronic Disease States", "glycan_involvement": "Glycosylation affects its protease inhibitory function.", "mechanism": "Alpha-2-macroglobulin is elevated in chronic inflammation, liver disease, and anemia.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691254" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation may affect albumin stability and clearance.", "mechanism": "Serum albumin levels decrease as liver synthetic function declines in fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate enzyme activity and serum half-life.", "mechanism": "Elevated AST reflects hepatocyte injury and is used in APRI index for fibrosis staging.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects platelet lifespan and clearance.", "mechanism": "Platelet count decreases with portal hypertension and splenic sequestration in fibrosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates enzyme localization and activity.", "mechanism": "Elevated GGT indicates cholestasis and hepatocellular injury in fibrosis.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen glycosylation affects fibril formation and ECM structure.", "mechanism": "Collagen deposition drives fibrotic remodeling and tissue stiffness.", "protein": "Collagen (fibrotic ECM glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12691310" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "miRNA transport and stability may be modulated by glycoprotein complexes.", "mechanism": "miRNAs regulate macrophage activation and fibrogenesis.", "protein": "MicroRNAs (miRNA-associated glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC12691310" }, { "confidence": "medium", "disease": "Autoimmune liver disease (AILD)", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Elevated immunoglobulins reflect autoimmune activity.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "medium", "disease": "Autoimmune liver disease (AILD)", "glycan_involvement": "Glycosylation affects antigen presentation and immune recognition.", "mechanism": "MHC glycoproteins present autoantigens, triggering immune-mediated liver injury.", "protein": "Major histocompatibility complex (MHC) glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12691310" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences bilirubin binding and transport.", "mechanism": "Altered bilirubin metabolism reflects impaired liver function.", "protein": "Bilirubin-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12691310" }, { "confidence": "high", "disease": "Portal hypertension", "glycan_involvement": "ECM glycosylation modulates vessel stiffness and permeability.", "mechanism": "Collagen deposition increases vascular resistance, leading to portal hypertension.", "protein": "Collagen (fibrotic ECM glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12691310" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns (e.g., AFP-L3) are linked to HCC progression.", "mechanism": "Elevated serum AFP is associated with increased risk and presence of HCC; used for diagnosis and monitoring.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation changes in AFP may help distinguish HCC from cirrhosis.", "mechanism": "AFP levels can be elevated in cirrhosis, but less specific than in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin is N-glycosylated; altered glycosylation may affect stability and function.", "mechanism": "Reduced serum albumin reflects impaired liver synthetic function in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "Altered glycoforms of AFP may improve specificity for HCC in MASLD.", "mechanism": "AFP may be used to monitor HCC risk in MASLD patients.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "medium", "disease": "Hepatitis B virus infection", "glycan_involvement": "Glycosylation status may help differentiate benign from malignant liver disease.", "mechanism": "AFP is elevated in HBV-infected patients at risk for HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "medium", "disease": "Hepatitis C virus infection", "glycan_involvement": "AFP glycoforms (e.g., AFP-L3) are more specific for HCC.", "mechanism": "AFP is used to monitor HCC development in HCV-infected patients.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation may reflect liver dysfunction.", "mechanism": "Low albumin is associated with poor prognosis in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691319" }, { "confidence": "high", "disease": "Cancer Stemness", "glycan_involvement": "CD44 glycosylation modulates ligand binding and cell migration.", "mechanism": "CD44 marks breast cancer stem cells, correlates with drug resistance and increased migration/invasion.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691352" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation affects CD44 function in cell adhesion and migration.", "mechanism": "Vitamin D analogs suppress CD44 expression via VDR, reducing stemness and tumor initiation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691352" }, { "confidence": "medium", "disease": "Tamoxifen Resistance", "glycan_involvement": "Glycosylation modulates MCAM-mediated cell adhesion.", "mechanism": "CD146\u2212 CAFs lower ER expression, increase tamoxifen resistance; CD146+ CAFs sustain sensitivity.", "protein": "CD146 (MCAM)", "protein_enriched": { "function": "Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of", "gene_name": "MCAM", "glycan_count": 26, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00912UN", "G04657PL", "G06356OH", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G45395BF", "G59626AS", "G62765YT", "G65184UU", "G70223PD", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G86880BF", "G93718GY", "G57321FI", "G25079LO", "G77669RF", "G89377PF" ], "uniprot_id": "P43121" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691352" }, { "confidence": "high", "disease": "Chemoresistance in Breast Cancer", "glycan_involvement": "Glycosylation influences receptor-ligand interactions.", "mechanism": "CD10+GPR77+ CAFs promote chemoresistance and stemness via sustained IL-6/IL-8 secretion.", "protein": "CD10 + GPR77", "relationship_type": "causal", "source_pmcid": "PMC12691352" }, { "confidence": "high", "disease": "Metastatic Breast Cancer", "glycan_involvement": "N-glycosylation critical for E-cadherin stability and adhesion.", "mechanism": "Vitamin D upregulates E-cadherin, suppresses metastasis and invasion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12691352" }, { "confidence": "medium", "disease": "Metastatic Breast Cancer", "glycan_involvement": "Glycosylation modulates cadherin-mediated cell interactions.", "mechanism": "Vitamin D downregulates P-cadherin, reducing mesenchymal phenotype and metastasis.", "protein": "P-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P22223" }, "relationship_type": "causal", "source_pmcid": "PMC12691352" }, { "confidence": "medium", "disease": "Metastatic Breast Cancer", "glycan_involvement": "N-glycosylation affects N-cadherin function in migration.", "mechanism": "Vitamin D downregulates N-cadherin, inhibiting EMT and metastasis.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12691352" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may affect receptor stability and signaling.", "mechanism": "VDR expression correlates with better prognosis; mediates anti-proliferative, pro-apoptotic, and anti-metastatic effects of vitamin D.", "protein": "VDR (Vitamin D Receptor)", "protein_enriched": { "function": "Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846).", "gene_name": "VDR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11473" }, "relationship_type": "protective", "source_pmcid": "PMC12691352" }, { "confidence": "medium", "disease": "Fibroblast Activation in Cancer", "glycan_involvement": "Glycosylation influences membrane localization.", "mechanism": "CAF subtypes in BC classified by caveolin-1 expression; relates to activation and tumor progression.", "protein": "Caveolin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the re", "gene_name": "Cav1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49817" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691352" }, { "confidence": "medium", "disease": "Fibroblast Activation in Cancer", "glycan_involvement": "N-glycosylation modulates receptor signaling.", "mechanism": "CAF subsets defined by PDGFR\u03b2; involved in stromal activation and tumor support.", "protein": "PDGFR\u03b2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic ", "gene_name": "PDGFRB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G48414YA", "G38663NM", "G52131KU", "G86500WE", "G49108TO" ], "uniprot_id": "P09619" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691352" }, { "confidence": "high", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Glycosylation affects secretion and stability of Chromogranin A, influencing its detectability.", "mechanism": "Chromogranin A is expressed by neuroendocrine cells and is used as a diagnostic marker for MCC.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "high", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Glycosylation is important for synaptophysin's membrane localization.", "mechanism": "Synaptophysin is a neuroendocrine marker expressed in MCC cells, aiding diagnosis.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "high", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Glycosylation may affect filament assembly and antigenicity.", "mechanism": "CK20 is characteristically expressed in MCC and helps distinguish it from other small round blue cell tumors.", "protein": "Cytokeratin 20 (CK20)", "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Glycosylation may influence serum stability.", "mechanism": "NSE is elevated in neuroendocrine tumors including MCC; used as a serum marker.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Polysialylation of NCAM1 modulates cell adhesion and metastatic potential.", "mechanism": "CD56 is expressed in neuroendocrine tumors including MCC, supporting diagnosis.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Plasmacytoma", "glycan_involvement": "Heparan sulfate glycosylation modulates cell adhesion and tumor microenvironment.", "mechanism": "CD138 is a marker for plasma cells and plasmacytoma, used in differential diagnosis with MCC.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "N-glycosylation affects CD20 surface expression.", "mechanism": "CD20 is a B-cell marker used to identify lymphomas in the differential diagnosis of MCC.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "N-glycosylation modulates TCR complex stability.", "mechanism": "CD3 is a T-cell marker used to distinguish T-cell lymphomas from MCC.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "medium", "disease": "Merkel cell carcinoma (MCC)", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Pan-cytokeratin cocktail (AE1/AE3) is positive in MCC, supporting epithelial origin.", "protein": "CK AE1/AE3", "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "low", "disease": "Metastatic melanoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "SOX10 is used to distinguish melanoma from MCC in differential diagnosis.", "protein": "SOX10", "protein_enriched": { "function": "Transcription factor that plays a central role in developing and mature glia (By similarity). Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15 ", "gene_name": "SOX10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691395" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "N-glycosylation modulates ligand binding and antibody recognition.", "mechanism": "Overexpressed in 80\u2013100% of HNSCC; targeted by cetuximab, ADCs, and bispecific antibodies.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "Immune checkpoint; blockade restores T cell activity (e.g., pembrolizumab, nivolumab).", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "EGFR inhibitor-resistant HNSCC", "glycan_involvement": "N-glycosylation required for proper folding and receptor function.", "mechanism": "Forms heterodimers with EGFR, mediating resistance; targeted by bispecific antibodies (e.g., SI-B001).", "protein": "HER3 (ERBB3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "N-glycosylation influences surface expression and antibody binding.", "mechanism": "Highly expressed on HNSCC cells; targeted by ADCs (e.g., tisotumab vedotin).", "protein": "Tissue Factor (TF/CD142)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation affects receptor stability and ligand interaction.", "mechanism": "Cancer stem cell marker; upregulated post-EGFR inhibition; targeted by bispecific antibody petosemtamab.", "protein": "LGR5", "protein_enriched": { "function": "Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2", "gene_name": "LGR5", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "O75473" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "EGFR inhibitor-resistant HNSCC", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Ligand for c-MET; drives resistance to EGFR inhibitors; targeted by ficlatuzumab.", "protein": "HGF", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01543ZX", "G11629QQ", "G17689DH", "G22310AV", "G48414YA", "G52126RR", "G52527GH", "G57789QC", "G60542VK", "G64394MX", "G74239ZQ", "G77252PU", "G89664KV", "G93656SY", "G45637XA", "G81006GJ", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G40834TG", "G41071NU", "G42124LM", "G45395BF", "G86880BF", "G90659AW", "G41247ZX", "G46691LC", "G62765YT", "G80920RR", "G83460ZZ" ], "uniprot_id": "P14210" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "EGFR inhibitor-resistant HNSCC", "glycan_involvement": "N-glycosylation critical for receptor maturation and function.", "mechanism": "Activated by HGF; mediates resistance and EMT; targeted indirectly via HGF blockade.", "protein": "c-MET", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "HPV-negative HNSCC", "glycan_involvement": "N-glycosylation essential for receptor trafficking and signaling.", "mechanism": "Upregulated in resistant tumors; targeted by NT219 (IRS1/2/STAT3 axis).", "protein": "IGF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691436" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding and cell adhesion.", "mechanism": "Cancer stem cell marker; associated with tumor progression and resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691436" }, { "confidence": "high", "disease": "Immunotherapy-refractory HNSCC", "glycan_involvement": "N-glycosylation shields PD-L1 from degradation, enhancing immune evasion.", "mechanism": "High PD-L1 expression predicts response to checkpoint inhibitors; resistance develops via TGF-\u03b2 and other pathways.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691436" }, { "confidence": "high", "disease": "Cancer-related anemia", "glycan_involvement": "Glycosylation required for stability and bioactivity", "mechanism": "Stimulates erythrocyte production to correct anemia in cancer patients", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691455" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation essential for receptor binding and function", "mechanism": "May promote tumor progression via EPO-R activation and pro-angiogenic effects", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "causal", "source_pmcid": "PMC12691455" }, { "confidence": "medium", "disease": "Head and neck cancer", "glycan_involvement": "Glycosylation affects receptor localization and ligand binding", "mechanism": "Variable EPO-R expression on tumor cells may be associated with worse outcomes in r-EPO-treated patients", "protein": "EPO Receptor (EPO-R)", "protein_enriched": { "function": "Receptor for erythropoietin, which mediates erythropoietin-induced erythroblast proliferation and differentiation (PubMed:10388848, PubMed:2163695, PubMed:2163696, PubMed:8662939, PubMed:9774108). Upo", "gene_name": "EPOR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P19235" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691455" }, { "confidence": "high", "disease": "Hepatocarcinoma", "glycan_involvement": "Glycosylation required for receptor function", "mechanism": "EPO/EPO-R axis in macrophages drives immunosuppression and poor antitumor immunity", "protein": "EPO Receptor (EPO-R)", "protein_enriched": { "function": "Receptor for erythropoietin, which mediates erythropoietin-induced erythroblast proliferation and differentiation (PubMed:10388848, PubMed:2163695, PubMed:2163696, PubMed:8662939, PubMed:9774108). Upo", "gene_name": "EPOR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P19235" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691455" }, { "confidence": "high", "disease": "Immunotherapy-refractory tumors", "glycan_involvement": "Glycosylation required for EPO stability and activity", "mechanism": "EPO exposure creates non-inflamed, T cell-deprived tumor microenvironment, reducing efficacy of checkpoint inhibitors", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "causal", "source_pmcid": "PMC12691455" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation required for EPO secretion and function", "mechanism": "Enhances angiogenesis via upregulation of VEGF and VEGF receptors in endothelial cells", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). 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As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691473" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation affects EGFR folding, trafficking, and ligand binding.", "mechanism": "Mutated EGFR drives tumor growth; targeted therapies inhibit EGFR signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691473" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation required for ALK receptor function and stability.", "mechanism": "ALK fusion proteins promote oncogenic signaling; ALK inhibitors block this pathway.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691473" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "N-glycosylation modulates CTLA-4 surface expression and immune checkpoint function.", "mechanism": "CTLA-4 inhibits T cell activation; blockade enhances anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691473" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "N-glycosylation influences PD-1 stability and ligand interaction.", "mechanism": "PD-1 on T cells binds PD-L1, suppressing immune response; inhibitors restore immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691473" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "CRP is heavily glycosylated, which affects its stability and function.", "mechanism": "Elevated CRP reflects systemic inflammation and correlates with poor prognosis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691473" }, { "confidence": "high", "disease": "Lung Cancer", "glycan_involvement": "N-glycosylation required for VEGF secretion and receptor binding.", "mechanism": "VEGF promotes angiogenesis, supporting tumor growth and metastasis.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12691473" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Glycosylation status may affect antibody binding and diagnostic accuracy.", "mechanism": "PD-L1 positivity predicts response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691473" }, { "confidence": "high", "disease": "Adenocarcinoma NSCLC", "glycan_involvement": "Glycosylation modulates EGFR activity and drug sensitivity.", "mechanism": "EGFR mutations are predictive of response to EGFR-targeted therapies.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691473" }, { "confidence": "medium", "disease": "Small Cell Lung Cancer (SCLC)", "glycan_involvement": "Glycosylation affects CRP's inflammatory activity.", "mechanism": "High CRP levels are associated with advanced disease and poor survival.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691473" }, { "confidence": "high", "disease": "Equine Infectious Anemia", "glycan_involvement": "Glycosylation of gp90 affects antigenicity and immune recognition.", "mechanism": "gp90 is a major envelope glycoprotein of EIAV; antibodies against gp90 are used for serological diagnosis.", "protein": "gp90", "relationship_type": "biomarker", "source_pmcid": "PMC12691497" }, { "confidence": "high", "disease": "Equine Infectious Anemia", "glycan_involvement": "Glycosylation modulates immune response and diagnostic sensitivity.", "mechanism": "gp45 is an envelope glycoprotein of EIAV; antibodies against gp45 are used in diagnostic assays.", "protein": "gp45", "relationship_type": "biomarker", "source_pmcid": "PMC12691497" }, { "confidence": "high", "disease": "Equine Infectious Anemia", "glycan_involvement": "Glycosylation may influence antigenicity and assay performance.", "mechanism": "p26 is a core glycoprotein of EIAV; detection of anti-p26 antibodies is the basis for ELISA and AGID diagnostic tests.", "protein": "p26", "relationship_type": "biomarker", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation of gp90 is essential for receptor binding and cell tropism.", "mechanism": "EIAV gp90 mediates viral entry into myeloid cells, leading to destruction of erythroid lineage and anemia.", "protein": "gp90", "relationship_type": "causal", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation affects viral infectivity and immune evasion.", "mechanism": "gp90-mediated EIAV infection of myeloid cells disrupts platelet production.", "protein": "gp90", "relationship_type": "causal", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Febrile episodes", "glycan_involvement": "Glycosylation modulates immune recognition and viral persistence.", "mechanism": "gp90 facilitates EIAV infection, leading to immune activation and recurrent fever.", "protein": "gp90", "relationship_type": "causal", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Weight loss", "glycan_involvement": "Glycosylation influences viral tropism and chronicity.", "mechanism": "gp90-driven EIAV infection causes chronic inflammation and cachexia.", "protein": "gp90", "relationship_type": "causal", "source_pmcid": "PMC12691497" }, { "confidence": "low", "disease": "Neurological manifestations", "glycan_involvement": "Glycosylation may affect tissue tropism.", "mechanism": "gp90 enables EIAV entry into cells, potentially leading to neurological symptoms.", "protein": "gp90", "relationship_type": "causal", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Equine Infectious Anemia", "glycan_involvement": "Glycosylation impacts vaccine efficacy and immune response.", "mechanism": "gp90 is targeted by neutralizing antibodies; vaccine strategies have focused on gp90.", "protein": "gp90", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691497" }, { "confidence": "medium", "disease": "Equine Infectious Anemia", "glycan_involvement": "Glycosylation affects antigenicity and immune targeting.", "mechanism": "gp45 is a target for immune response and diagnostic assays.", "protein": "gp45", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691497" }, { "confidence": "high", "disease": "Oligodendroglioma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "IDH1 mutation leads to 2-hydroxyglutarate accumulation, driving tumorigenesis; targeted by IDH inhibitors.", "protein": "IDH1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12691507" }, { "confidence": "high", "disease": "Oligodendroglioma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "IDH2 mutation also leads to 2-hydroxyglutarate accumulation, driving tumorigenesis; targeted by IDH inhibitors.", "protein": "IDH2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12691507" }, { "confidence": "high", "disease": "Oligodendroglioma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "MGMT promoter methylation predicts response to PCV chemotherapy.", "protein": "MGMT", "relationship_type": "biomarker", "source_pmcid": "PMC12691507" }, { "confidence": "medium", "disease": "Oligodendroglioma", "glycan_involvement": "NOTCH1 is a glycoprotein; glycosylation may affect receptor function, but not specified here.", "mechanism": "NOTCH1 alterations may confer resistance to IDH inhibitors.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "resistance mechanism", "source_pmcid": "PMC12691507" }, { "confidence": "medium", "disease": "Oligodendroglioma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "CDKN2A deletion associated with poor response to PCV chemotherapy.", "protein": "CDKN2A", "relationship_type": "biomarker/resistance", "source_pmcid": "PMC12691507" }, { "confidence": "low", "disease": "Glioma", "glycan_involvement": "NOTCH1 glycosylation may modulate signaling, but not detailed in this article.", "mechanism": "NOTCH1 alterations implicated in resistance to targeted therapies.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "resistance mechanism", "source_pmcid": "PMC12691507" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects HDL structure and function.", "mechanism": "Low HDL is associated with MASLD presence and progression.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycosylation modulates receptor binding and clearance.", "mechanism": "Elevated LDL contributes to atherosclerosis risk in MASLD.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects glycemic control, which is linked to MASLD and CVD risk.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "medium", "disease": "Hepatic Fibrosis", "glycan_involvement": "N-glycosylation affects stability and clearance.", "mechanism": "Altered transthyretin levels may indicate liver dysfunction and fibrosis.", "protein": "Transthyretin", "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates SGLT2 membrane localization.", "mechanism": "SGLT2 inhibitors reduce hepatic steatosis and fibrosis.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT is associated with hepatic inflammation and fibrosis.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated AST is associated with hepatic inflammation and fibrosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "medium", "disease": "Hepatic Fibrosis", "glycan_involvement": "N-glycosylation affects albumin half-life.", "mechanism": "Low albumin indicates advanced liver disease and fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates insulin receptor binding.", "mechanism": "Insulin resistance drives MASLD pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12691519" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects troponin stability.", "mechanism": "Troponin I elevation may indicate subclinical cardiac injury in MASLD.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691519" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "IL-33 is a glycoprotein; glycosylation may affect secretion and receptor binding.", "mechanism": "IL-33 is upregulated in senescent chondrocytes and mediates hypertrophy, matrix degradation, and osteogenic gene expression, driving OA progression.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "high", "disease": "Cartilage degeneration", "glycan_involvement": "Glycosylation may regulate IL-33 stability and release.", "mechanism": "IL-33 promotes chondrocyte hypertrophy and extracellular matrix breakdown under mechanical stress.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "medium", "disease": "Subchondral bone sclerosis", "glycan_involvement": "Glycosylation may influence IL-33's interaction with osteogenic pathways.", "mechanism": "IL-33 induces osteogenic differentiation in chondrocytes, contributing to subchondral bone remodeling.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "medium", "disease": "Osteophyte formation", "glycan_involvement": "Glycosylation may affect IL-33's extracellular activity.", "mechanism": "IL-33 upregulates hypertrophic and osteogenic markers, promoting osteophyte development.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "ST2 is a glycoprotein; glycosylation may modulate ligand binding and signaling.", "mechanism": "ST2 is the receptor for IL-33; its engagement activates downstream inflammatory and osteogenic signaling in OA.", "protein": "Suppressor of Tumorigenicity 2 (ST2/IL1RL1)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "high", "disease": "Cartilage degeneration", "glycan_involvement": "MMP13 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "MMP13 is upregulated by IL-33 and FSS, mediating cartilage matrix breakdown.", "protein": "Matrix Metalloproteinase 13 (MMP13)", "relationship_type": "biomarker", "source_pmcid": "PMC12691701" }, { "confidence": "medium", "disease": "Subchondral bone sclerosis", "glycan_involvement": "RUNX2 is glycosylated; glycosylation may regulate transcriptional activity.", "mechanism": "RUNX2 is upregulated by IL-33, promoting osteogenic differentiation and bone sclerosis.", "protein": "Runt-related transcription factor 2 (RUNX2)", "relationship_type": "biomarker", "source_pmcid": "PMC12691701" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "ACAN is a proteoglycan; glycosylation is essential for ECM structure.", "mechanism": "ACAN expression is decreased in senescent/IL-33-stimulated chondrocytes, indicating cartilage degeneration.", "protein": "Aggrecan (ACAN)", "relationship_type": "biomarker", "source_pmcid": "PMC12691701" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "COL2A1 is glycosylated; glycosylation affects fibril formation.", "mechanism": "COL2A1 is downregulated in OA and by IL-33, marking cartilage loss.", "protein": "Type II Collagen (COL2A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691701" }, { "confidence": "medium", "disease": "Joint inflammation", "glycan_involvement": "Glycosylation may modulate IL-33's immunogenicity.", "mechanism": "IL-33 acts as an alarmin, activating immune cells and amplifying joint inflammation.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "causal", "source_pmcid": "PMC12691701" }, { "confidence": "high", "disease": "Non-obstructive azoospermia (NOA)", "glycan_involvement": "AMH is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Serum AMH reflects Sertoli cell function and is negatively associated with sperm retrieval rate in NOA patients undergoing TESE.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Klinefelter syndrome", "glycan_involvement": "Glycosylation required for AMH bioactivity.", "mechanism": "Low serum AMH indicates Sertoli/germ cell dysfunction; below threshold predicts negative sperm retrieval in non-mosaic Klinefelter syndrome.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Sertoli cell-only syndrome (SCOS)", "glycan_involvement": "Glycosylation affects AMH secretion from Sertoli cells.", "mechanism": "Markedly reduced AMH reflects absence/immaturity of Sertoli cells in SCOS.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Obstructive azoospermia (OA)", "glycan_involvement": "Glycosylation required for AMH detection in fluids.", "mechanism": "Seminal AMH is undetectable in OA, helping distinguish OA from NOA.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Non-obstructive azoospermia (NOA)", "glycan_involvement": "Inhibin B is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "Low inhibin B correlates with reduced probability of successful sperm retrieval in NOA.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Non-obstructive azoospermia (NOA)", "glycan_involvement": "FSH is a glycoprotein; glycosylation modulates receptor binding and half-life.", "mechanism": "Elevated FSH reflects testicular failure but has limited predictive accuracy for sperm retrieval.", "protein": "Follicle-Stimulating Hormone (FSH)", "protein_enriched": { "function": "Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled recepto", "gene_name": "FSHB", "glycan_count": 28, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08146BT", "G32246SI", "G79745PG", "G90789YQ", "G05850WN", "G43753QH", "G45495MK", "G50131RA", "G51177EP", "G51497BL", "G06356OH", "G15169WU", "G16155TD", "G17689DH", "G22310AV", "G45209NR", "G45560HM", "G47518TP", "G48414YA", "G52527GH", "G56318NV", "G66088HZ", "G69834CE", "G77252PU", "G78030KJ", "G91413ZX", "G94531EZ", "G98366ZJ" ], "uniprot_id": "P01225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Oligozoospermia", "glycan_involvement": "Glycosylation required for AMH stability and function.", "mechanism": "Lower AMH levels are associated with reduced sperm count and quality.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Idiopathic NOA", "glycan_involvement": "Glycosylation impacts AMH measurement and function.", "mechanism": "Elevated AMH/testosterone ratio may indicate germ cell depletion in idiopathic NOA.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "low", "disease": "Klinefelter syndrome", "glycan_involvement": "Glycosylation required for inhibin B secretion.", "mechanism": "Low inhibin B reflects Sertoli cell dysfunction in Klinefelter syndrome.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691789" }, { "confidence": "medium", "disease": "Non-obstructive azoospermia (NOA)", "glycan_involvement": "Glycosylation of both AMH and inhibin B essential for their function and measurement.", "mechanism": "Combined AMH/inhibin B or AMH/testosterone ratios improve predictive accuracy for sperm retrieval over single markers.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker (combined)", "source_pmcid": "PMC12691789" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "VEGF-A is a glycoprotein; glycosylation is required for secretion and receptor binding.", "mechanism": "Promotes angiogenesis, tumor growth, and progression via binding to VEGFR-2.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12691807" }, { "confidence": "high", "disease": "Metastatic colorectal cancer (mCRC)", "glycan_involvement": "Glycosylation affects VEGF-A stability and bioactivity.", "mechanism": "Targeted by anti-angiogenic drugs (e.g., bevacizumab) to inhibit tumor vascularization.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Lymph node metastasis", "glycan_involvement": "VEGF-D is a glycoprotein; glycosylation influences receptor interaction.", "mechanism": "VEGF-D expression correlates with regional lymph node metastasis in CRC.", "protein": "VEGF-D", "protein_enriched": { "function": "Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May functi", "gene_name": "VEGFD", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43915" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691807" }, { "confidence": "high", "disease": "Metastatic colorectal cancer (mCRC)", "glycan_involvement": "N-glycosylation required for proper folding and ligand binding.", "mechanism": "VEGFR-2 mediates angiogenic signaling; targeted by ramucirumab and fruquintinib.", "protein": "VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Metastatic colorectal cancer (mCRC)", "glycan_involvement": "Isoform-specific glycosylation may affect receptor affinity.", "mechanism": "Certain isoforms predict response to bevacizumab therapy.", "protein": "VEGF-A splice isoforms (165b, 121)", "relationship_type": "biomarker", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "PlGF glycosylation modulates receptor binding.", "mechanism": "Enhances angiogenesis and immune suppression via VEGFR-1 signaling.", "protein": "PlGF", "relationship_type": "causal", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "Involved in tumor-associated angiogenesis and immune modulation.", "protein": "VEGFR-1", "relationship_type": "causal", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Lymph node metastasis", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Promotes lymphangiogenesis via VEGFR-3, facilitating metastasis.", "protein": "VEGF-C", "relationship_type": "causal", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation modulates ligand binding.", "mechanism": "Acts as a co-receptor for VEGF, enhancing angiogenic signaling.", "protein": "Neuropilin-1", "relationship_type": "causal", "source_pmcid": "PMC12691807" }, { "confidence": "medium", "disease": "Metastatic colorectal cancer (mCRC)", "glycan_involvement": "N-glycosylation affects receptor shedding and serum levels.", "mechanism": "High circulating VEGFR-2 levels predict better response to bevacizumab.", "protein": "VEGFR-2", "relationship_type": "biomarker", "source_pmcid": "PMC12691807" }, { "confidence": "high", "disease": "X-linked Adrenoleukodystrophy (X-ALD)", "glycan_involvement": "No direct glycosylation mechanism described for ALDP in this article.", "mechanism": "Loss-of-function mutations in ABCD1 impair peroxisomal import of VLCFA, causing their accumulation and neurodegeneration.", "protein": "Adrenoleukodystrophy Protein (ALDP/ABCD1)", "relationship_type": "causal", "source_pmcid": "PMC12691817" }, { "confidence": "high", "disease": "Adrenomyeloneuropathy (AMN)", "glycan_involvement": "MPZ is a glycoprotein; glycosylation is essential for myelin compaction and stability.", "mechanism": "MPZ promoter used for Schwann cell-specific gene therapy targeting peripheral myelin repair in AMN.", "protein": "Myelin Protein Zero (MPZ)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691817" }, { "confidence": "medium", "disease": "Cerebral Adrenoleukodystrophy (cALD)", "glycan_involvement": "S100B is a glycoprotein; glycosylation may affect secretion and receptor interaction.", "mechanism": "S100B promoter enables astrocyte-specific gene therapy; S100B modulates neuronal survival via RAGE signaling.", "protein": "S100 Calcium-binding Protein Beta (S100B)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691817" }, { "confidence": "medium", "disease": "Cerebral Adrenoleukodystrophy (cALD)", "glycan_involvement": "MAG is a glycoprotein; glycosylation is critical for myelin-axon interactions.", "mechanism": "MAG promoter used for oligodendrocyte-specific gene therapy to support myelin integrity.", "protein": "Myelin Associated Glycoprotein (MAG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691817" }, { "confidence": "medium", "disease": "Cerebral Adrenoleukodystrophy (cALD)", "glycan_involvement": "GFAP is a glycoprotein; glycosylation may influence filament assembly.", "mechanism": "GFAP promoter used for astrocyte-specific gene therapy to restore glial support.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691817" }, { "confidence": "high", "disease": "Adrenomyeloneuropathy (AMN)", "glycan_involvement": "No direct glycosylation mechanism described for ALDP in this article.", "mechanism": "ABCD1 deficiency in spinal cord glia leads to VLCFA accumulation, oxidative stress, and axonal degeneration.", "protein": "Adrenoleukodystrophy Protein (ALDP/ABCD1)", "relationship_type": "causal", "source_pmcid": "PMC12691817" }, { "confidence": "high", "disease": "Cerebral Adrenoleukodystrophy (cALD)", "glycan_involvement": "No direct glycosylation mechanism described for ALDP in this article.", "mechanism": "ABCD1 loss in microglia and astrocytes triggers neuroinflammation and demyelination.", "protein": "Adrenoleukodystrophy Protein (ALDP/ABCD1)", "relationship_type": "causal", "source_pmcid": "PMC12691817" }, { "confidence": "high", "disease": "Addison\u2019s Disease (Primary Adrenal Insufficiency in X-ALD)", "glycan_involvement": "No direct glycosylation mechanism described for ALDP in this article.", "mechanism": "ABCD1 deficiency in adrenal cortex cells impairs VLCFA metabolism, leading to adrenal insufficiency.", "protein": "Adrenoleukodystrophy Protein (ALDP/ABCD1)", "relationship_type": "causal", "source_pmcid": "PMC12691817" }, { "confidence": "medium", "disease": "X-linked Adrenoleukodystrophy (X-ALD)", "glycan_involvement": "MPZ glycosylation is required for myelin sheath formation.", "mechanism": "MPZ promoter activity reflects Schwann cell/myelin status in peripheral neuropathy.", "protein": "Myelin Protein Zero (MPZ)", "relationship_type": "biomarker", "source_pmcid": "PMC12691817" }, { "confidence": "medium", "disease": "X-linked Adrenoleukodystrophy (X-ALD)", "glycan_involvement": "S100B glycosylation may modulate extracellular signaling.", "mechanism": "S100B levels may indicate astrocyte activation and neuroinflammation.", "protein": "S100 Calcium-binding Protein Beta (S100B)", "relationship_type": "biomarker", "source_pmcid": "PMC12691817" }, { "confidence": "high", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation required for cell surface expression and ligand binding.", "mechanism": "Elevated in acute DVT; mediates leukocyte adhesion and platelet activation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "high", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "N-glycosylation modulates adhesion and immune cell recruitment.", "mechanism": "Increased in chronic DVT; indicates persistent endothelial dysfunction.", "protein": "sVCAM-1", "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "high", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "N-glycosylation affects ligand binding and immune interactions.", "mechanism": "Elevated after 6 months; reflects ongoing endothelial activation.", "protein": "sICAM-1", "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation influences receptor binding and stability.", "mechanism": "Elevated in acute DVT; promotes vascular remodeling and inflammation.", "protein": "PDGF-AB/BB", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "N-glycosylation affects secretion and receptor interaction.", "mechanism": "Increased in acute DVT; drives inflammatory response.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Elevated in acute DVT; recruits neutrophils to thrombus site.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "low", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Likely N-glycosylation; impacts serum stability.", "mechanism": "Altered serum levels in DVT up to 2 years post-event.", "protein": "Glycoprotein A", "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "low", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Potential glycosylation modulates immune function.", "mechanism": "Emerging marker; associated with inflammation in DVT.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation affects plasma half-life.", "mechanism": "Reflects ongoing fibrinolysis; used to rule out DVT.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "low", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "Measured in plasma; involved in vascular response.", "protein": "sVEGFR-2", "relationship_type": "biomarker", "source_pmcid": "PMC12691825" }, { "confidence": "high", "disease": "AA amyloidosis", "glycan_involvement": "SAA is a glycoprotein; glycosylation may affect its stability and aggregation.", "mechanism": "Chronic inflammation or malignancy induces sustained SAA overproduction, leading to extracellular amyloid fibril deposition.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "Renal dysfunction", "glycan_involvement": "Glycosylation may influence SAA's deposition and clearance.", "mechanism": "AA amyloid deposits in the kidney cause proteinuria and renal impairment.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "medium", "disease": "Cardiac amyloidosis", "glycan_involvement": "Glycosylation may modulate SAA aggregation in cardiac tissue.", "mechanism": "AA amyloid deposits in cardiac tissue lead to wall thickening and dysfunction.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Glycosylation may affect SAA's tissue tropism.", "mechanism": "AA amyloid deposits in nerves cause peripheral nerve injury.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "AA amyloidosis secondary to thymoma", "glycan_involvement": "SAA glycosylation may affect its amyloidogenicity.", "mechanism": "Thymoma-driven chronic inflammation and cytokine release (notably IL-6) induce SAA overproduction and systemic amyloid deposition.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "AA amyloidosis", "glycan_involvement": "IL-6 is glycosylated, which affects its secretion and receptor binding.", "mechanism": "IL-6 stimulates hepatic SAA production, promoting amyloidogenesis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "AA amyloidosis", "glycan_involvement": "SAP glycosylation is important for its binding to amyloid fibrils.", "mechanism": "SAP is a universal constituent of amyloid deposits, stabilizing amyloid fibrils.", "protein": "Serum Amyloid P-component", "relationship_type": "biomarker", "source_pmcid": "PMC12691831" }, { "confidence": "medium", "disease": "AA amyloidosis", "glycan_involvement": "ApoE glycosylation affects its interaction with amyloid fibrils.", "mechanism": "ApoE is found in amyloid deposits and may modulate amyloidogenesis.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "Amyloid light chain amyloidosis", "glycan_involvement": "Light chains are glycoproteins; glycosylation influences aggregation.", "mechanism": "Misfolded light chains aggregate as amyloid in tissues (not the main mechanism in this case).", "protein": "Immunoglobulin light chain (kappa/lambda)", "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "Transthyretin amyloidosis", "glycan_involvement": "Transthyretin is glycosylated; glycosylation affects aggregation.", "mechanism": "Misfolded transthyretin forms amyloid deposits (excluded in this case).", "protein": "Transthyretin", "relationship_type": "causal", "source_pmcid": "PMC12691831" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of proteins; altered glycan structures.", "mechanism": "AGEs accumulate due to hyperglycemia, contributing to diabetic complications.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Diabetic Vascular Complications", "glycan_involvement": "Glycation alters protein function and cell signaling.", "mechanism": "AGEs promote endothelial dysfunction and microvascular damage.", "protein": "AGEs", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12691836" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect enzyme stability/activity.", "mechanism": "Decreased SOD activity reflects oxidative stress in diabetes.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691836" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "CAT activity changes indicate oxidative stress status.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691836" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation may influence enzyme function.", "mechanism": "Reduced GPx activity is associated with increased oxidative damage.", "protein": "Glutathione Peroxidase (GPx)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Oxidative modification of glycoproteins.", "mechanism": "Elevated AOPP levels indicate protein oxidation in diabetes.", "protein": "AOPP", "relationship_type": "biomarker", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Insulin is glycosylated; glycan structure affects secretion/stability.", "mechanism": "Autoimmune destruction of insulin-producing cells leads to diabetes.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Diabetic Dyslipidemia", "glycan_involvement": "Glycation and glycosylation alter LDL function and clearance.", "mechanism": "Elevated LDL and its glycation/oxidation contribute to vascular complications.", "protein": "LDL", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691836" }, { "confidence": "medium", "disease": "Diabetic Dyslipidemia", "glycan_involvement": "Glycosylation modulates HDL function.", "mechanism": "Reduced HDL levels in diabetes; HDL glycosylation affects anti-atherogenic properties.", "protein": "HDL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycation alters albumin structure and function.", "mechanism": "Albumin is a major target for glycation and oxidation (AGEs, AOPP).", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691836" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 interacts with HSPGs via glycan chains, promoting aggregation.", "mechanism": "A\u03b2 aggregation forms plaques, central to AD pathology; decreased CSF A\u03b242 reflects plaque sequestration.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691845" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated, which may affect aggregation and pathology.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles; increased CSF and plasma p-tau isoforms correlate with disease progression.", "protein": "Tau (MAPT)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691845" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE is N-glycosylated, influencing lipid transport and aggregation.", "mechanism": "ApoE4 allele increases AD risk; ApoE fragments affect mitochondria and amyloid pathology.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "genetic risk/biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "HS glycan chains mediate A\u03b2 binding and aggregation.", "mechanism": "HSPGs (e.g., syndecans) promote A\u03b2 oligomerization and plaque formation via HS chains; modulate neuroinflammation.", "protein": "Heparan sulfate proteoglycans (HSPGs)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects lactoferrin stability and transport.", "mechanism": "Salivary lactoferrin levels decrease in AD; found in A\u03b2 plaques and NFTs.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates \u03b12M function and clearance.", "mechanism": "Serum \u03b12M correlates with cognitive decline and tau/p-tau levels; linked to vascular dysfunction.", "protein": "Alpha-2-macroglobulin (\u03b12M)", "relationship_type": "biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects ApoA-1 function and BBB crossing.", "mechanism": "Lower ApoA-1 in AD serum/CSF; modulates A\u03b2 aggregation and cerebrovascular integrity.", "protein": "Apolipoprotein A1 (ApoA-1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for afamin secretion and stability.", "mechanism": "Afamin transports vitamin E; downregulated in AD, increasing vulnerability to oxidative stress.", "protein": "Afamin", "protein_enriched": { "function": "Acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation (PubMed:16772533). In presence of estrogen, binds to ESR1-responsive promoters (PubM", "gene_name": "WBP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969T9" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Mannosylation (N-glycan) modification increases in AD, impacting transferrin function.", "mechanism": "Man-Tf elevated in AD CSF; correlates with p-tau, reflects ER stress and neuronal dysfunction.", "protein": "Mannosylated-glycan transferrin (Man-Tf)", "relationship_type": "biomarker", "source_pmcid": "PMC12691845" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates IGFBP2 stability and bioactivity.", "mechanism": "High plasma IGFBP2 associated with AD risk and brain atrophy.", "protein": "Insulin-like growth factor binding protein 2 (IGFBP2)", "relationship_type": "biomarker/risk", "source_pmcid": "PMC12691845" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from APP, a glycoprotein; glycosylation of APP affects A\u03b2 production and aggregation.", "mechanism": "A\u03b2 aggregation and deposition in brain and CSF; decreased CSF A\u03b242 is a diagnostic biomarker; aggregates cause neurotoxicity.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation and toxicity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles; increased CSF tau correlates with disease progression.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Alpha-synuclein can be O-glycosylated; glycosylation affects aggregation propensity.", "mechanism": "Aggregation and deposition in neurons; reduced CSF \u03b1-synuclein is a biomarker; oligomeric forms correlate with motor decline.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "ALS", "glycan_involvement": "N-glycosylation modulates neurofilament stability and turnover.", "mechanism": "Elevated CSF NfL reflects neuronal damage and correlates with ALS progression.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is N-glycosylated; glycosylation regulates enzyme activity and trafficking.", "mechanism": "BACE1 cleaves APP to generate A\u03b2; increased CSF BACE1 is a biomarker and therapeutic target.", "protein": "BACE1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691848" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "DJ-1 is glycosylated; glycosylation may affect stability and function.", "mechanism": "CSF DJ-1 levels are altered in PD; involved in oxidative stress response.", "protein": "DJ-1 (PARK7)", "relationship_type": "biomarker", "source_pmcid": "PMC12691848" }, { "confidence": "medium", "disease": "ALS", "glycan_involvement": "TDP-43 can be O-glycosylated; glycosylation may modulate aggregation.", "mechanism": "Mutant/aggregated TDP-43 found in CSF; drives neurodegeneration in ALS.", "protein": "TDP-43", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Huntington's disease", "glycan_involvement": "Huntingtin is N-glycosylated; glycosylation influences aggregation and toxicity.", "mechanism": "Mutant huntingtin detected in CSF; correlates with disease severity and progression.", "protein": "Mutant huntingtin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob disease", "glycan_involvement": "14-3-3 proteins are not classically glycosylated; glycan involvement is minimal.", "mechanism": "Elevated CSF 14-3-3 is diagnostic for CJD; reflects rapid neuronal damage.", "protein": "14-3-3 protein", "protein_enriched": { "function": "Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or p", "gene_name": "YWHAB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P31946" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691848" }, { "confidence": "medium", "disease": "Multiple system atrophy", "glycan_involvement": "O-glycosylation may affect aggregation and disease specificity.", "mechanism": "CSF \u03b1-synuclein levels overlap with PD and MSA; used for differential diagnosis.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691848" }, { "confidence": "high", "disease": "Epithelial Ovarian Cancer", "glycan_involvement": "N-glycosylation required for secretion and receptor activation.", "mechanism": "Promotes ovarian cancer cell proliferation via TSHR activation, cAMP, ERK, AKT, and EGFR transactivation.", "protein": "Thyrostimulin (GPA2/GPB5)", "relationship_type": "causal", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "Elevated circulating GPB5 correlates with insulin resistance and metabolic dysfunction in PCOS.", "protein": "GPB5", "relationship_type": "biomarker", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Metabolic Syndrome", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "Serum GPB5 levels are elevated and correlate with BMI, blood pressure, glucose, and insulin; reduced by GLP-1RA therapy.", "protein": "GPB5", "relationship_type": "biomarker", "source_pmcid": "PMC12691860" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "Overexpression in mice leads to reduced body weight, adiposity, and improved metabolic rate.", "protein": "GPB5", "relationship_type": "protective", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "Elevated GPB5 correlates with HOMA-IR and reduced insulin sensitivity.", "protein": "GPB5", "relationship_type": "biomarker", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Skeletal Development Disorders", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Acts as a negative regulator of osteoblastic bone formation during early development; knockout increases bone volume.", "protein": "Thyrostimulin (GPA2/GPB5)", "relationship_type": "causal", "source_pmcid": "PMC12691860" }, { "confidence": "medium", "disease": "Congenital Hypothyroidism", "glycan_involvement": "N-glycosylation required for TSH\u03b2 and GPB5 function.", "mechanism": "Mutations in TSH\u03b2 (related glycoprotein) cause defective TSH bioactivity and congenital hypothyroidism; GPB5 may act as alternative TSHR ligand.", "protein": "GPB5", "relationship_type": "causal", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Growth Defects (C. elegans)", "glycan_involvement": "Cystine knot formation (glycan-dependent folding) required for function.", "mechanism": "Knockout leads to impaired growth and reduced body length via neuroendocrine signaling.", "protein": "Thyrostimulin orthologs (GPLA-2/GPLB-5)", "relationship_type": "causal", "source_pmcid": "PMC12691860" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "Elevated GPB5 in diabetic mice; correlates with metabolic dysfunction.", "protein": "GPB5", "relationship_type": "biomarker", "source_pmcid": "PMC12691860" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation at Asn63 required for expression.", "mechanism": "GPB5 associated with increased risk of atherosclerosis in PCOS/metabolic syndrome context.", "protein": "GPB5", "relationship_type": "biomarker", "source_pmcid": "PMC12691860" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "YKL-40 is a glycoprotein; glycosylation is essential for secretion and function.", "mechanism": "Elevated serum levels correlate with tumor progression, poor differentiation, and recurrence risk; promotes inflammation, angiogenesis, and EMT.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation required for extracellular activity and receptor interactions.", "mechanism": "Amplifies inflammatory response, stimulates PI3K/AKT/mTOR and ERK1/2 pathways, promotes tumor growth, angiogenesis, and metastasis.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "causal", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation may affect immunogenicity and therapeutic targeting.", "mechanism": "Targeting YKL-40 may reduce tumor progression and improve prognosis.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation required for stability and secretion.", "mechanism": "Elevated levels associated with neuroinflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Increased levels reflect chronic inflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may affect hormone stability and receptor binding.", "mechanism": "Elevated RLN2 promotes metastasis, angiogenesis, and ECM remodeling; inhibition reduces invasiveness.", "protein": "Relaxin-2 (RLN2)", "protein_enriched": { "function": "Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellula", "gene_name": "FKBP4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q02790" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation may affect local activity; serum levels not diagnostic.", "mechanism": "RLN2 modulates tumor microenvironment, enhances immune cell infiltration, and may improve immunotherapy efficacy.", "protein": "Relaxin-2 (RLN2)", "protein_enriched": { "function": "Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellula", "gene_name": "FKBP4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q02790" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691882" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CEA is heavily glycosylated; glycan structures affect detection and function.", "mechanism": "Serum levels correlate strongly with disease stage and progression.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CA 19-9 is a glycan epitope (sialyl-Lewis A) on glycoproteins.", "mechanism": "Elevated in advanced/metastatic CRC; limited sensitivity for early disease.", "protein": "CA 19-9", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:17502375, PubMed:22932902). Mediates transport of beta-alanine (PubMed:17502375). Can also mediate transport", "gene_name": "SLC6A13", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NSD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Elevated levels reflect intestinal inflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12691882" }, { "confidence": "high", "disease": "Pre-Osteoarthritis (pre-OA)", "glycan_involvement": "Aggrecan's chondroitin sulfate and keratan sulfate glycosylation are lost early.", "mechanism": "Early loss of aggrecan and its glycosaminoglycan chains impairs cartilage hydration and resilience, marking subclinical matrix degradation.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "O-glycosylation critical for lubricating function.", "mechanism": "Reduced PRG4 levels in synovial fluid decrease cartilage lubrication, increasing mechanical wear and OA risk.", "protein": "PRG4 (Lubricin)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "HA interacts with glycoproteins (e.g., aggrecan, PRG4) for matrix integrity.", "mechanism": "Decreased HA in synovial fluid impairs joint lubrication and shock absorption, contributing to OA progression.", "protein": "Hyaluronan (HA)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "COMP is a glycoprotein; glycosylation affects stability and ECM interactions.", "mechanism": "Elevated serum COMP predicts incident OA years before radiographic changes.", "protein": "COMP", "relationship_type": "biomarker", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Pre-Osteoarthritis (pre-OA)", "glycan_involvement": "Cleavage of glycosylated aggrecan core protein.", "mechanism": "Upregulation of aggrecanases leads to early aggrecan degradation in cartilage.", "protein": "ADAMTS aggrecanases", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Target glycosylated ECM proteins.", "mechanism": "MMPs degrade collagen and proteoglycans, accelerating cartilage breakdown.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12691886" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Collagen glycosylation affects fibril stability.", "mechanism": "Early collagen network disruption marks irreversible cartilage damage.", "protein": "Type II Collagen", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691886" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Elevated IL-6 drives inflammation and upregulates catabolic enzymes in OA.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691886" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "IL-1\u03b2 promotes catabolic enzyme expression, leading to ECM breakdown.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12691886" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Glycosylation influences TNF-\u03b1 stability and signaling.", "mechanism": "TNF-\u03b1 induces inflammation and catabolic pathways in OA.", "protein": "Tumor Necrosis Factor-\u03b1 (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12691886" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "SHBG is a glycoprotein; glycosylation is essential for its stability and hormone-binding function.", "mechanism": "Genetic variants (e.g., GG genotype at rs440837 in ZBTB10) raise SHBG levels, reducing free testosterone and estrogens, which increases endometriosis risk.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "causal", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Uterine Fibroids", "glycan_involvement": "Glycosylation maintains SHBG structure and hormone transport capacity.", "mechanism": "GG genotype at rs440837 in ZBTB10 increases SHBG levels, associated with higher risk of uterine fibroids.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "causal", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation affects SHBG's hormone-binding and plasma half-life.", "mechanism": "GWAS-significant SHBG polymorphisms are associated with breast cancer risk, possibly via altered hormone bioavailability.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691900" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation required for SHBG secretion and function in plasma.", "mechanism": "Elevated SHBG levels and mRNA expression in endometriotic tissue correlate with disease presence and severity.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation may influence SHBG's response to therapy.", "mechanism": "SHBG modulation (e.g., via danazol treatment) reduces SHBG levels and alleviates endometriosis symptoms.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691900" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation stabilizes SHBG and its hormone-binding domains.", "mechanism": "SHBG protects estrogens from metabolic inactivation, increasing local estrogen availability in endometrial cells.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "causal", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation is necessary for SHBG's regulatory functions.", "mechanism": "SHBG-raising SNPs interact epistatically, affecting endocrine system development, TGF-beta signaling, and cell proliferation relevant to endometriosis.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "causal", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation may affect SHBG isoform secretion and function.", "mechanism": "SHBG mRNA splicing variants are dominantly expressed in ovarian endometriosis.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation supports SHBG's stability and interaction with other proteins.", "mechanism": "SHBG genetic determinants (e.g., ZBTB10 region) regulate transcription factors and pathways (e.g., TGF-beta) implicated in endometriosis.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "causal", "source_pmcid": "PMC12691900" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Reduced glycosylation may decrease SHBG stability and hormone binding.", "mechanism": "Certain SHBG-lowering genotypes (e.g., A allele at rs440837) are associated with reduced endometriosis risk.", "protein": "Sex Hormone-Binding Globulin", "relationship_type": "protective", "source_pmcid": "PMC12691900" }, { "confidence": "high", "disease": "Alcohol-associated liver disease (ALD)", "glycan_involvement": "CXCL9 is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "CXCL9 is upregulated in ALD, correlates with severity and poor prognosis by promoting Th1 cell recruitment and IFN-gamma-mediated responses.", "protein": "CXCL9 (MIG)", "protein_enriched": { "function": "Activity is required in presynaptic neurons, in a dose-dependent manner, for normal presynaptic development and morphology (PubMed:15707898). Plays a role in the formation of muscle connections, also ", "gene_name": "mkk-4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q20347" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Alcohol-associated liver disease (ALD)", "glycan_involvement": "CXCL10 is a glycoprotein; glycosylation may regulate receptor binding and immune cell trafficking.", "mechanism": "CXCL10 is upregulated in ALD, correlates with severity and short-term mortality by recruiting effector T cells and enhancing inflammation.", "protein": "CXCL10 (IP-10)", "relationship_type": "biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may modulate chemokine stability and activity.", "mechanism": "Elevated CXCL9 predicts poor survival in cirrhosis and decreases after portal decompression (TIPS).", "protein": "CXCL9 (MIG)", "protein_enriched": { "function": "Activity is required in presynaptic neurons, in a dose-dependent manner, for normal presynaptic development and morphology (PubMed:15707898). Plays a role in the formation of muscle connections, also ", "gene_name": "mkk-4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q20347" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may affect chemokine-receptor interactions.", "mechanism": "High CXCL10 levels associate with poor survival and portal hypertension; inhibition reduces fibrosis.", "protein": "CXCL10 (IP-10)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "medium", "disease": "Alcohol-associated liver disease (ALD)", "glycan_involvement": "CXCL16 is a glycoprotein; glycosylation may influence scavenger receptor function.", "mechanism": "CXCL16 is upregulated in ALD and correlates with systemic inflammation (CRP, leukocytosis), but not with disease severity.", "protein": "CXCL16", "relationship_type": "biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation may regulate CXCL16 receptor binding and cell recruitment.", "mechanism": "CXCL16/CXCR6 axis drives hepatic NKT cell recruitment, amplifying inflammation and promoting fibrogenesis.", "protein": "CXCL16", "relationship_type": "causal", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Glycosylation may affect chemokine secretion and immune cell targeting.", "mechanism": "CXCL10 is specifically upregulated in AH, correlates with neutrophil infiltration and portal hypertension.", "protein": "CXCL10 (IP-10)", "relationship_type": "biomarker", "source_pmcid": "PMC12691941" }, { "confidence": "medium", "disease": "Viral hepatitis", "glycan_involvement": "Glycosylation may modulate chemokine activity.", "mechanism": "CXCL16 is upregulated in viral hepatitis, promoting lymphocyte recruitment and fibrosis.", "protein": "CXCL16", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12691941" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may regulate immune cell interactions.", "mechanism": "CXCL10 facilitates T cell migration in autoimmune diseases; inhibition may benefit T1DM and other T cell\u2013driven disorders.", "protein": "CXCL10 (IP-10)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12691941" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation may influence chemokine stability and antifibrotic activity.", "mechanism": "CXCL9 may suppress fibrogenic markers (\u03b1-SMA, Collagen-I/III), exerting antifibrotic effects under certain conditions.", "protein": "CXCL9 (MIG)", "protein_enriched": { "function": "Activity is required in presynaptic neurons, in a dose-dependent manner, for normal presynaptic development and morphology (PubMed:15707898). Plays a role in the formation of muscle connections, also ", "gene_name": "mkk-4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q20347" }, "relationship_type": "protective", "source_pmcid": "PMC12691941" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects XOR stability and localization.", "mechanism": "XOR generates ROS in plaques, promoting endothelial injury and inflammation.", "protein": "Xanthine oxidoreductase (XOR)", "protein_enriched": { "function": "Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has a", "gene_name": "XDH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P47989" }, "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates MCP-1 secretion and activity.", "mechanism": "XOR upregulates MCP-1, driving monocyte recruitment and plaque progression.", "protein": "Monocyte chemotactic protein-1 (MCP-1)", "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for IL-1\u03b2 secretion.", "mechanism": "Uric acid activates NLRP3 inflammasome via TLR4, increasing IL-1\u03b2 and impairing insulin signaling.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects IL-6 stability and receptor binding.", "mechanism": "Elevated uric acid correlates with increased IL-6 in circulation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion.", "mechanism": "HU increases TNF-\u03b1, promoting inflammation and insulin resistance.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for TLR4 surface expression.", "mechanism": "Uric acid activates TLR4, triggering NLRP3 inflammasome and inflammatory cytokines.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation may regulate complex assembly.", "mechanism": "Activated by uric acid, leading to IL-1\u03b2 production and inflammation.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects LDL receptor binding and clearance.", "mechanism": "Elevated LDL in HU contributes to plaque formation.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates HDL function.", "mechanism": "Lower HDL in HU reduces reverse cholesterol transport.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12691944" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation essential for VCAM-1 function.", "mechanism": "HU-induced inflammation upregulates VCAM-1, promoting leukocyte adhesion.", "protein": "Vascular cell adhesion molecule 1 (VCAM-1)", "relationship_type": "causal", "source_pmcid": "PMC12691944" }, { "confidence": "high", "disease": "Acne Vulgaris", "glycan_involvement": "N-glycosylation affects RBP stability and serum transport.", "mechanism": "Retinoids regulate RBP expression and retinoid transport, influencing skin cell differentiation and inflammation.", "protein": "Retinol Binding Protein (RBP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "Acne Vulgaris", "glycan_involvement": "Glycosylation critical for laminin function in extracellular matrix.", "mechanism": "Retinoic acid modulates laminin gene expression, impacting basement membrane integrity and skin repair.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Minor N-glycosylation may affect enzyme stability.", "mechanism": "Vitamin E supplementation increases catalase activity, reducing oxidative stress in joint tissues.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12691958" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates SOD secretion and activity.", "mechanism": "Carotenoids and tocopherols upregulate SOD, lowering oxidative damage in vascular tissues.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "Cognitive Decline", "glycan_involvement": "Glycosylation required for enzyme activity.", "mechanism": "Lutein and zeaxanthin supplementation increase glutathione peroxidase, protecting neurons from oxidative stress.", "protein": "Glutathione Peroxidase", "relationship_type": "protective", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "UV-induced Skin Damage", "glycan_involvement": "Glycosylation affects TRPV1 trafficking and function.", "mechanism": "Capsaicin activates TRPV1, enhancing Nrf2 pathway and antioxidant defense in skin cells.", "protein": "TRPV1", "protein_enriched": { "function": "Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:11050376, PubMed:11243859, PubMed:11226139, PubMed:12077606). Seems to mediate proto", "gene_name": "TRPV1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NER1" }, "relationship_type": "protective", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "Acne Vulgaris", "glycan_involvement": "Glycosylation may influence receptor localization and ligand binding.", "mechanism": "Retinoids bind to retinoic acid receptor, modulating gene expression for skin cell turnover.", "protein": "Retinoic Acid Receptor", "protein_enriched": { "function": "Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in resp", "gene_name": "RARA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10276" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691958" }, { "confidence": "low", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation required for enzyme stability.", "mechanism": "Capsaicin and CoQ10 supplementation restore glutathione reductase activity, reducing neuroinflammation.", "protein": "Glutathione Reductase", "relationship_type": "protective", "source_pmcid": "PMC12691958" }, { "confidence": "low", "disease": "Depression", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Retinoic acid regulates alcohol dehydrogenase, influencing neurotransmitter metabolism.", "protein": "Alcohol Dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12691958" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "O-glycosylation modulates keratin filament assembly.", "mechanism": "Retinoids regulate keratin gene expression, improving skin barrier function.", "protein": "Keratin", "protein_enriched": { "function": "May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity recept", "gene_name": "KRT1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI", "G22310AV", "G48414YA", "G75983OB" ], "uniprot_id": "P04264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691958" }, { "confidence": "high", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Glycosylation affects CD19 surface expression and antibody recognition.", "mechanism": "CD19 is highly expressed on B-ALL blasts and is targeted by bispecific antibodies (blinatumomab) and CAR-T therapies.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Glycosylation modulates ligand binding and antibody targeting.", "mechanism": "CD22 is expressed on B-ALL cells and is targeted by antibody-drug conjugates (inotuzumab ozogamicin).", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL)", "glycan_involvement": "Glycosylation influences antibody binding and immune clearance.", "mechanism": "CD38 is aberrantly expressed in subsets of T-ALL and targeted by monoclonal antibody daratumumab.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691962" }, { "confidence": "medium", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Glycosylation affects antigenicity and detection.", "mechanism": "CD10 is expressed in most B-ALL cases; absence is associated with MLL translocations and poor prognosis.", "protein": "CD10", "protein_enriched": { "function": "Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhi", "gene_name": "CD72", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX" ], "uniprot_id": "P21854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691962" }, { "confidence": "medium", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Glycosylation may affect antibody binding.", "mechanism": "CD20 is expressed in a subset of B-ALL and is associated with poor prognosis in adults.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "N-glycosylation is essential for MHC class II function.", "mechanism": "HLA-DR is universally expressed in B-ALL and used for immunophenotyping.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Heavily glycosylated; sialylation affects cell adhesion and migration.", "mechanism": "CD34 marks precursor B-ALL cells and is used for diagnosis.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691962" }, { "confidence": "medium", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "CD79a is expressed in B-ALL and used for lineage determination.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "Philadelphia chromosome-like ALL (Ph-like ALL)", "glycan_involvement": "Glycosylation required for receptor function and signaling.", "mechanism": "CRLF2 rearrangements activate JAK-STAT and PI3K/AKT/mTOR pathways, driving leukemogenesis.", "protein": "CRLF2", "protein_enriched": { "function": "Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates", "gene_name": "CRLF2", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q9HC73" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL), Early T-cell Progenitor ALL (ETP-ALL)", "glycan_involvement": "Glycosylation modulates receptor stability and ligand binding.", "mechanism": "Activating mutations in IL7R drive JAK-STAT signaling and leukemic cell survival.", "protein": "IL7R", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12691962" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "PD-L1 glycosylation modulates its stability and immune recognition.", "mechanism": "Upregulation of PD-L1 in cardiomyocytes triggers T-cell mediated immune attack after ICI therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Glycosylation may affect troponin clearance and detection.", "mechanism": "Elevated troponin I indicates myocardial injury in ICI-associated myocarditis.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12691975" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation influences Tenascin-C's ECM interactions.", "mechanism": "High Tenascin-C expression in myocardial biopsies reflects tissue remodeling and inflammation.", "protein": "Tenascin-C", "relationship_type": "biomarker", "source_pmcid": "PMC12691975" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation regulates CTLA-4 cell surface expression.", "mechanism": "CTLA-4 signaling is cardioprotective; its inhibition by ICIs increases myocarditis risk.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "protective", "source_pmcid": "PMC12691975" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation affects CD86 ligand binding.", "mechanism": "Abatacept blocks CD86-mediated T-cell costimulation, reducing immune-mediated myocarditis.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Glycosylation modulates TCR signaling and cell migration.", "mechanism": "CD3+ T-cell infiltration drives cardiac inflammation in ICI-associated myocarditis.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Glycosylation affects CD4 stability and immune interactions.", "mechanism": "CD4+ T-helper cells secrete pro-inflammatory cytokines, contributing to myocarditis.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Glycosylation modulates CD8 function and antigen recognition.", "mechanism": "CD8+ cytotoxic T cells directly damage cardiomyocytes in ICI-associated myocarditis.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation influences macrophage activation and migration.", "mechanism": "CD68+ macrophage infiltration amplifies cardiac inflammation and tissue injury.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "Cardiotoxicity", "glycan_involvement": "PD-L1 glycosylation affects its immune checkpoint function.", "mechanism": "PD-L1 inhibition by ICIs disrupts immune tolerance, increasing risk of cardiac irAEs.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12691975" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "FGF21 expression is increased in metabolically unhealthy lean (MUL) and obese (MUO) individuals, indicating impaired energy homeostasis and compensatory hepatic response.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691983" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "O-GlcNAcylation regulates ChREBP activity and nuclear localization.", "mechanism": "Liver ChREBP\u03b2 expression positively correlates with HOMA-IR index, linking it to insulin resistance.", "protein": "ChREBP\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12691983" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "O-GlcNAcylation modulates PPAR\u03b1 transcriptional activity.", "mechanism": "Low hepatic PPAR\u03b1 expression in MUL correlates with steatosis; PPAR\u03b1 agonists may restore lipid homeostasis.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691983" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "O-GlcNAcylation enhances ChREBP\u03b2 activity under high glucose.", "mechanism": "Upregulation of ChREBP\u03b2 in liver is associated with increased lipogenesis and hepatic steatosis.", "protein": "ChREBP\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12691983" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation may influence FGF21 receptor binding and function.", "mechanism": "FGF21 upregulation is an adaptive response to metabolic stress, improving insulin sensitivity.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12691983" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "Elevated serum GGT levels are associated with MASLD and metabolic dysfunction.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12691983" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "CRP is heavily glycosylated; glycosylation modulates its immune function.", "mechanism": "High-sensitivity CRP (>3 mg/L) is elevated in MASLD, indicating inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12691983" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-GlcNAcylation regulates ChREBP\u03b2 function in response to glucose.", "mechanism": "ChREBP\u03b2 upregulation in liver and downregulation in adipose tissue reflect tissue-specific metabolic adaptation in obesity.", "protein": "ChREBP\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12691983" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "O-GlcNAcylation may affect PPAR\u03b1-mediated gene regulation.", "mechanism": "PPAR\u03b1 agonists improve glycemia and protect liver in non-obese patients with T2D and MASLD.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12691983" }, { "confidence": "low", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may affect FGF21 stability and therapeutic efficacy.", "mechanism": "FGF21 analogs reduce liver fat and improve fibrosis, potentially lowering CVD risk.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12691983" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation enables stability, bioavailability, and blood-brain barrier crossing.", "mechanism": "Preserves neuronal morphology, stabilizes microtubules, restores dopaminergic markers, enhances antioxidant defenses, reduces \u03b1-synuclein aggregation, and restores iron homeostasis.", "protein": "Bovine Lactoferrin (bLf, Native form)", "relationship_type": "protective", "source_pmcid": "PMC12692066" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation maintains structure but iron saturation state alters function.", "mechanism": "Increases labile iron pool, induces pro-oxidative responses, and aggravates \u03b1-synuclein aggregation.", "protein": "Bovine Lactoferrin (bLf, Holo form)", "relationship_type": "causal/exacerbating", "source_pmcid": "PMC12692066" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation affects stability and bioavailability; less effective than bLf due to glycan differences.", "mechanism": "Reduces oxidative stress and apoptosis in rotenone-induced PD models.", "protein": "Human Lactoferrin (hLf)", "relationship_type": "protective", "source_pmcid": "PMC12692066" }, { "confidence": "high", "disease": "Neurodegeneration (general)", "glycan_involvement": "Glycosylation critical for function and stability.", "mechanism": "Reduces oxidative DNA and lipid damage, supports antioxidant enzyme expression.", "protein": "Bovine Lactoferrin (bLf, Native form)", "relationship_type": "protective", "source_pmcid": "PMC12692066" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Not glycosylated; aggregation modulated by glycoprotein-mediated iron homeostasis.", "mechanism": "Aggregation is a hallmark of PD; increased by iron and oxidative stress.", "protein": "\u03b1-Synuclein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692066" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Downregulated in PD; restored by bLf, improving iron homeostasis.", "protein": "Divalent Metal Transporter-1 (DMT-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692066" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Downregulated in PD; upregulated by bLf, promoting iron export.", "protein": "Ferroportin (Fpn)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692066" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Downregulated in PD; restored by bLf, enhancing antioxidant defense.", "protein": "Superoxide Dismutase 2 (SOD-2)", "relationship_type": "protective", "source_pmcid": "PMC12692066" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Loss is a hallmark of dopaminergic neuron degeneration; restored by bLf.", "protein": "Tyrosine Hydroxylase (TH)", "relationship_type": "biomarker", "source_pmcid": "PMC12692066" }, { "confidence": "high", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation essential for CNS delivery and function.", "mechanism": "Multifunctional neuroprotection via iron chelation, antioxidant activity, and inhibition of protein aggregation.", "protein": "Bovine Lactoferrin (bLf, Native form)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692066" }, { "confidence": "high", "disease": "Post-viral neuroinflammation", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Reflects monocyte\u2013macrophage activation and sustained innate immune activity after viral infection.", "protein": "CD14 (soluble form, presepsin)", "relationship_type": "biomarker", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Neuropathic pain (NP)", "glycan_involvement": "N-glycosylation essential for secretion and bridging activity.", "mechanism": "Bridges phosphatidylserine on apoptotic cells to integrins on macrophages; impaired function leads to defective efferocytosis and persistent inflammation.", "protein": "MFG-E8", "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Neuropathic pain (NP)", "glycan_involvement": "\u03b3-carboxylation and glycosylation required for receptor binding.", "mechanism": "Activates MerTK/Axl signaling to promote efferocytosis and resolution; deficiency perpetuates inflammation and pain.", "protein": "Gas6", "protein_enriched": { "function": "Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various ", "gene_name": "GAS6", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G83460ZZ", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G49108TO" ], "uniprot_id": "Q14393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Post-viral neuroinflammation", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "Mediates efferocytosis; viral interference with Axl impairs apoptotic cell clearance, sustaining neuroinflammation.", "protein": "Axl receptor tyrosine kinase", "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Neuropathic pain (NP)", "glycan_involvement": "N-glycosylation required for function and stability.", "mechanism": "Key efferocytosis receptor; downregulation or cleavage leads to defective clearance and chronic pain.", "protein": "MerTK", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological proce", "gene_name": "MERTK", "glycan_count": 28, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G62461SM", "G10486CT", "G11629QQ", "G37399XV", "G59626AS", "G65184UU", "G80920RR", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G56784JY", "G57888GL", "G62765YT", "G02815KT", "G23010ZW", "G02030ZB", "G10019LZ", "G12580WI", "G15169WU", "G22310AV", "G38663NM", "G52527GH", "G83460ZZ", "G84452RH", "G06356OH", "G29068FM", "G43417UB" ], "uniprot_id": "Q12866" }, "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "Impaired TREM2 signaling reduces microglial clearance of neuronal debris, promoting neurodegeneration.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation affects SIRP\u03b1 binding.", "mechanism": "Overexpressed on tumor cells; interacts with SIRP\u03b1 to inhibit macrophage phagocytosis, enabling immune evasion.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for ligand recognition.", "mechanism": "Binds CD47 on tumor cells, transmitting 'don't eat me' signal to macrophages.", "protein": "SIRP\u03b1", "protein_enriched": { "function": "Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhe", "gene_name": "SIRPA", "glycan_count": 49, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G25451PN", "G45395BF", "G57776ZS", "G79666IR", "G82501QM", "G84452RH", "G87123QX", "G93718GY", "G96577RX", "G06356OH", "G10486CT", "G20210JR", "G23294PN", "G27058EU", "G40926MX", "G59626AS", "G65184UU", "G75983OB", "G80223IX", "G80920RR", "G82463GQ", "G83646BJ", "G49108TO", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G11314AS", "G18647XP", "G28541PG", "G31852PQ", "G37399XV", "G37995HC", "G39188ZX", "G39446WN", "G41071NU", "G41247ZX", "G49018RC", "G57776ZU", "G59924QI", "G72747WU", "G92406TI", "G95865ZB", "G00406II", "G00912UN", "G09831WQ", "G35541EV", "G82364UA" ], "uniprot_id": "P78324" }, "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "medium", "disease": "Post-viral neuroinflammation", "glycan_involvement": "Glycosylation status not specified; protein-protein interaction is key.", "mechanism": "Masks phosphatidylserine on apoptotic cells, inhibiting efferocytosis and promoting inflammation.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "N-glycosylation modulates ligand binding and signaling.", "mechanism": "Binds HMGB1 and advanced glycation end-products, amplifying inflammatory signaling and inhibiting efferocytosis.", "protein": "RAGE (AGER)", "relationship_type": "causal", "source_pmcid": "PMC12692071" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Heavy O-glycosylation critical for antigenicity and detection.", "mechanism": "Serum CA125 levels reflect tumor burden and recurrence risk.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Serum HE4 improves specificity for ovarian cancer diagnosis and recurrence monitoring.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation modulates cell adhesion and immune recognition.", "mechanism": "EpCAM expression on CTCs enables detection and monitoring of residual disease.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune checkpoint function.", "mechanism": "PD-L1 upregulation mediates immune evasion and is associated with poor prognosis.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation may affect protein stability and localization.", "mechanism": "Loss of MLH1 detected by IHC indicates mismatch repair deficiency and recurrence risk.", "protein": "MLH1", "protein_enriched": { "function": "Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t", "gene_name": "MLH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P40692" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Potential glycosylation impacts function.", "mechanism": "MSH2 loss marks dMMR phenotype, guiding prognosis and therapy.", "protein": "MSH2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismat", "gene_name": "MSH2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50713DU", "G21891JQ", "G49108TO" ], "uniprot_id": "P43246" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "Glycosylation modulates adhesion and EMT.", "mechanism": "N-cadherin upregulation during EMT promotes metastasis.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12692091" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation affects filament assembly and detection.", "mechanism": "Cytokeratin-positive CTCs correlate with treatment response and recurrence risk.", "protein": "Cytokeratins", "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "N-glycosylation regulates PD-L1 stability.", "mechanism": "PD-L1 expression stratifies patients for immunotherapy.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Cancer recurrence", "glycan_involvement": "Glycosylation influences serum detectability.", "mechanism": "Elevated HE4 levels predict recurrence in gynecologic cancers.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692091" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "PSMA is a glycoprotein; its glycosylation is essential for proper folding, stability, and cell surface expression, which impacts ligand binding and therapeutic efficacy.", "mechanism": "PSMA is highly overexpressed on prostate cancer cells, enabling selective targeting by radioligand therapies (e.g., Lu-PSMA-617) for delivery of cytotoxic radiation.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692093" }, { "confidence": "high", "disease": "Metastatic hormone-sensitive prostate cancer (mHSPC)", "glycan_involvement": "Glycosylation affects PSMA's cell surface localization and imaging agent binding.", "mechanism": "PSMA expression is used for PET imaging to identify and monitor metastatic prostate cancer lesions.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692093" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Overexpression inhibits apoptosis, promotes cell proliferation, and mediates resistance to chemo- and radiotherapy.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/biomarker/causal", "source_pmcid": "PMC12692146" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Upregulated, especially in triple-negative subtype; inhibits apoptosis and promotes metastasis.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/biomarker/causal", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeted by bispecific proteins and small molecule inhibitors; mediates resistance to EGFR inhibitors.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeted by peptide vaccines to induce immune responses and disease control.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeted by peptide vaccines; limited clinical benefit observed.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeted by multi-antigen T cell therapies; associated with durable remission in some patients.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeted by dendritic cell vaccines to boost anti-survivin immunity post-transplant.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Survivin-derived peptides induce CTL responses; targeted by bispecific proteins.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Survivin-specific T cells detected in patients; peptide vaccines induce immune responses.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "O-glycosylation critical for immune recognition and function.", "mechanism": "Included as a target in multi-antigen immunotherapy (CV9202); induces antigen-specific immune responses.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692146" }, { "confidence": "high", "disease": "Childhood obesity", "glycan_involvement": "Bifidobacterium glycoproteins mediate adhesion and immune modulation; PCP acts as substrate for glycan metabolism.", "mechanism": "PCP increases Bifidobacterium abundance, which is reduced in obese children; associated with improved SCFA and indolelactic acid production.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Surface glycoproteins facilitate mucosal interaction and glycan utilization.", "mechanism": "PCP increases Limosilactobacillus, which produces indolelactic acid, activating AhR and supporting barrier integrity.", "protein": "Limosilactobacillus surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycoproteins involved in carbohydrate metabolism and SCFA production.", "mechanism": "Enhanced Bifidobacterium leads to increased acetic acid, supporting metabolic regulation.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Produced via microbial glycan metabolism of tryptophan.", "mechanism": "Indolelactic acid activates AhR, promoting immune regulation and reducing inflammation.", "protein": "Indolelactic acid", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Glycoproteins mediate substrate utilization and host interaction.", "mechanism": "Enterococcus expansion in obese children may reflect dysbiosis; PCP modulates its abundance.", "protein": "Enterococcus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12692152" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Produced by glycan fermentation by gut bacteria.", "mechanism": "Acetic acid supports barrier function and is increased by PCP via glycoprotein-expressing bacteria.", "protein": "Acetic acid", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "high", "disease": "Dysbiosis", "glycan_involvement": "Glycoproteins mediate glycan uptake and colonization.", "mechanism": "PCP restores Bifidobacterium in obese children, counteracting dysbiosis.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycoproteins facilitate glycan metabolism.", "mechanism": "Limosilactobacillus expansion increases SCFA and indolelactic acid, supporting metabolic health.", "protein": "Limosilactobacillus surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "medium", "disease": "Childhood obesity", "glycan_involvement": "Derived from glycan metabolism by gut bacteria.", "mechanism": "PCP increases indolelactic acid, which is reduced in obesity and supports metabolic and immune functions.", "protein": "Indolelactic acid", "relationship_type": "protective", "source_pmcid": "PMC12692152" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycoproteins involved in host interaction and immune response.", "mechanism": "Enterococcus expansion may contribute to inflammation in obese children; PCP modulates its abundance.", "protein": "Enterococcus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12692152" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "HLA class II is a glycoprotein; glycosylation is essential for its structure and immune recognition.", "mechanism": "Soluble HLA class II interacts with CD4 on monocytes, inducing CD16 expression and promoting antibody-dependent cytotoxicity and inflammation.", "protein": "HLA class II", "relationship_type": "causal", "source_pmcid": "PMC12692172" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "HLA class I is a glycoprotein; glycosylation affects immune modulation.", "mechanism": "Soluble HLA-B blocks induction of CD16 on monocytes, suppressing cytotoxicity and inflammation.", "protein": "HLA class I (HLA-B)", "relationship_type": "protective", "source_pmcid": "PMC12692172" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "CD16 is glycosylated; glycosylation modulates receptor function and antibody binding.", "mechanism": "Elevated CD16+ monocytes correlate with PE severity and systemic inflammation.", "protein": "CD16 (Fc\u03b3RIII)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692172" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Allelic variation may affect glycosylation and antigen presentation.", "mechanism": "Maternal allele strongly associated with increased risk of PE.", "protein": "HLA-DRB1*01:01:01G", "relationship_type": "biomarker", "source_pmcid": "PMC12692172" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Allelic variation may affect glycosylation and immune response.", "mechanism": "Allele more frequent in controls, suggesting reduced risk of PE.", "protein": "HLA-DQB1*06:03:01G", "relationship_type": "protective", "source_pmcid": "PMC12692172" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "CD4 is glycosylated; glycosylation affects ligand binding.", "mechanism": "CD4 on monocytes interacts with soluble HLA class II, triggering CD16 expression and cytotoxicity.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12692172" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "sFlt-1 is glycosylated; glycosylation affects stability and function.", "mechanism": "Elevated sFlt-1 contributes to endothelial dysfunction in PE.", "protein": "sFlt-1", "relationship_type": "biomarker", "source_pmcid": "PMC12692172" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Endoglin is glycosylated; glycosylation modulates receptor activity.", "mechanism": "Increased soluble endoglin promotes vascular injury in PE.", "protein": "soluble endoglin", "protein_enriched": { "function": "Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (P", "gene_name": "ENG", "glycan_count": 6, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G53434XO", "G43417UB", "G45395BF", "G62765YT", "G49108TO" ], "uniprot_id": "P17813" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692172" }, { "confidence": "medium", "disease": "Transplant rejection", "glycan_involvement": "Glycosylation required for antigen presentation and immune activation.", "mechanism": "Soluble HLA class II activates monocyte cytotoxicity, contributing to rejection.", "protein": "HLA class II", "relationship_type": "causal", "source_pmcid": "PMC12692172" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects immune recognition and therapeutic efficacy.", "mechanism": "Manipulation of soluble HLA class I may enhance monocyte cytotoxicity against tumors.", "protein": "HLA class I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692172" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Extensive N-glycosylation shields epitopes from antibodies, facilitating immune evasion.", "mechanism": "Mediates viral entry by binding CD4 and coreceptors; high antigenic variability enables immune evasion.", "protein": "Env (gp160/gp120/gp41)", "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "high", "disease": "AIDS", "glycan_involvement": "Glycan shield impairs neutralising antibody responses, contributing to disease progression.", "mechanism": "Drives CD4 T cell depletion via cell entry and cytopathic effects.", "protein": "Env (gp160/gp120/gp41)", "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "HIV-associated dementia (HAD)", "glycan_involvement": "Glycosylation may affect Env neuroinvasion and immune recognition in CNS.", "mechanism": "Env and Tat proteins implicated in neurotoxicity after CNS entry.", "protein": "Env (gp160/gp120/gp41)", "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation of CD4 affects Env binding affinity and viral tropism.", "mechanism": "Primary receptor for HIV entry; depletion leads to immunodeficiency.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation modulates receptor function and viral tropism.", "mechanism": "Coreceptor for HIV entry; CCR5\u039432 mutation confers resistance.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "Rapid progression HIV", "glycan_involvement": "Glycosylation influences coreceptor usage and viral tropism.", "mechanism": "X4-tropic viruses associated with faster disease progression.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Sialic acid-dependent glycan recognition facilitates viral capture and transmission.", "mechanism": "DC Siglec receptors mediate HIV recognition and transinfection.", "protein": "Siglec", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation required for antiviral function and membrane localization.", "mechanism": "Restricts viral release; antagonised by Vpu.", "protein": "BST-2 (Tetherin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "Elite control HIV", "glycan_involvement": "Altered glycosylation may reduce infectivity and immune evasion.", "mechanism": "Poorly functional Env genes (low fusogenicity/affinity) linked to elite control phenotype.", "protein": "Env (gp160/gp120/gp41)", "relationship_type": "protective", "source_pmcid": "PMC12692205" }, { "confidence": "high", "disease": "Vaccine failure", "glycan_involvement": "Dense N-glycosylation masks conserved epitopes, limiting vaccine efficacy.", "mechanism": "Antigenic variability and glycan shield preclude effective vaccine-induced neutralising antibodies.", "protein": "Env (gp160/gp120/gp41)", "relationship_type": "causal", "source_pmcid": "PMC12692205" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "A2M is a glycoprotein; glycosylation may affect stability and anti-inflammatory function.", "mechanism": "TGR5 activation upregulates A2M, which is anti-neuroinflammatory in microglia; TGR5 agonists reduce MS severity.", "protein": "A2M (Alpha-2-macroglobulin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "AHSG is a glycoprotein; glycosylation may modulate its anti-inflammatory activity.", "mechanism": "TGR5 activation increases AHSG expression, contributing to anti-inflammatory microglial phenotype.", "protein": "AHSG (Alpha-2-HS-glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect CNS transport and function.", "mechanism": "TGR5 activation upregulates ALB, which may contribute to neuroprotection and anti-inflammation.", "protein": "ALB (Albumin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "APOA1 is glycosylated; glycosylation may influence lipid transport and immune modulation.", "mechanism": "TGR5 activation increases APOA1, which is anti-inflammatory and neuroprotective.", "protein": "APOA1 (Apolipoprotein A-I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "APOH is highly glycosylated; glycosylation is critical for its immune regulatory functions.", "mechanism": "TGR5 activation upregulates APOH, contributing to anti-inflammatory microglial responses.", "protein": "APOH (Beta-2-glycoprotein 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "SPP2 is a glycoprotein; glycosylation may affect secretion and function.", "mechanism": "TGR5 activation increases SPP2, which is associated with anti-inflammatory effects in microglia.", "protein": "SPP2 (Secreted phosphoprotein 2)", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio", "gene_name": "TUBA1C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BQE3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692218" }, { "confidence": "low", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "A2M glycosylation affects its protease inhibitor and amyloid-binding functions.", "mechanism": "Altered bile acid signaling may modulate A2M levels, which are linked to amyloid-beta clearance and inflammation.", "protein": "A2M (Alpha-2-macroglobulin)", "relationship_type": "biomarker", "source_pmcid": "PMC12692218" }, { "confidence": "low", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "Glycosylation modulates APOA1\u2019s CNS transport and function.", "mechanism": "Bile acid signaling influences APOA1, which is involved in amyloid-beta transport and neuroprotection.", "protein": "APOA1 (Apolipoprotein A-I)", "relationship_type": "biomarker", "source_pmcid": "PMC12692218" }, { "confidence": "low", "disease": "Parkinson\u2019s Disease", "glycan_involvement": "Glycosylation is essential for APOH\u2019s immune and aggregation-modulating roles.", "mechanism": "Bile acid-induced modulation of APOH may affect neuroinflammation and alpha-synuclein aggregation.", "protein": "APOH (Beta-2-glycoprotein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12692218" }, { "confidence": "low", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "A2M glycosylation may modulate its neuroprotective and anti-inflammatory properties.", "mechanism": "Altered bile acid metabolism may affect A2M levels, which are linked to neuroinflammation and neuronal survival.", "protein": "A2M (Alpha-2-macroglobulin)", "relationship_type": "biomarker", "source_pmcid": "PMC12692218" }, { "confidence": "high", "disease": "DPP4 inhibitor-associated bullous pemphigoid (DPP4i-BP)", "glycan_involvement": "DPP4 is a glycoprotein; glycosylation affects its stability and immune regulatory function.", "mechanism": "Genetic variants (rs3788979 T allele, CT/TT genotypes) associated with reduced DPP4 expression and serum levels, increasing susceptibility to BP upon gliptin exposure.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "causal", "source_pmcid": "PMC12692233" }, { "confidence": "medium", "disease": "Classic bullous pemphigoid (cBP)", "glycan_involvement": "Glycosylation modulates DPP4\u2019s immune signaling properties.", "mechanism": "rs12617656 TC genotype associated with increased risk of cBP, possibly via immune dysregulation.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "causal", "source_pmcid": "PMC12692233" }, { "confidence": "medium", "disease": "Bullous pemphigoid (BP)", "glycan_involvement": "Glycosylation state may influence DPP4 localization and function.", "mechanism": "Altered serum and tissue levels of DPP4 observed in BP patients; membrane-bound DPP4 increased in lesions, soluble DPP4 decreased systemically.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC12692233" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation required for proper folding and enzymatic activity.", "mechanism": "DPP4 is targeted by gliptins for glycemic control.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692233" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect immune cell interactions.", "mechanism": "rs12617656 variant linked to increased risk of rheumatoid arthritis in GWAS.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "causal", "source_pmcid": "PMC12692233" }, { "confidence": "high", "disease": "Bullous pemphigoid (BP)", "glycan_involvement": "BP180 is glycosylated; glycan structures may influence antigenicity.", "mechanism": "Autoantibodies target BP180, leading to dermoepidermal separation and blister formation.", "protein": "BP180 (Type XVII collagen)", "relationship_type": "causal", "source_pmcid": "PMC12692233" }, { "confidence": "high", "disease": "Bullous pemphigoid (BP)", "glycan_involvement": "Glycosylation may affect protein stability and immune recognition.", "mechanism": "Autoantibodies against BP230 contribute to BP pathogenesis.", "protein": "BP230", "protein_enriched": { "function": "Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleto", "gene_name": "DST", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q03001" }, "relationship_type": "causal", "source_pmcid": "PMC12692233" }, { "confidence": "medium", "disease": "DPP4 inhibitor-associated bullous pemphigoid (DPP4i-BP)", "glycan_involvement": "Glycosylation may modulate DPP4\u2019s immune regulatory function.", "mechanism": "TT haplotype (T alleles at rs3788979 and rs12617656) confers increased risk for DPP4i-BP.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "pharmacogenetic risk", "source_pmcid": "PMC12692233" }, { "confidence": "low", "disease": "Bullous pemphigoid (BP)", "glycan_involvement": "Glycosylation required for soluble DPP4 function.", "mechanism": "Higher serum DPP4 levels may protect against BP by maintaining immune tolerance.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "protective", "source_pmcid": "PMC12692233" }, { "confidence": "low", "disease": "Bullous pemphigoid (BP)", "glycan_involvement": "Glycosylation affects DPP4\u2019s stability and detectability.", "mechanism": "Serum DPP4 levels may serve as a biomarker for BP risk and disease activity.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC12692233" }, { "confidence": "high", "disease": "Inherited Retinal Dystrophies (IRDs)", "glycan_involvement": "Glycosylation affects Prom1 localization and function in RPE.", "mechanism": "Loss-of-function mutations cause RPE and photoreceptor degeneration via impaired autophagy, mitochondrial turnover, and junctional stability.", "protein": "Prominin-1 (CD133)", "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "high", "disease": "Atrophic Age-Related Macular Degeneration (aAMD)", "glycan_involvement": "Glycosylation modulates Prom1 membrane/cytoplasmic distribution.", "mechanism": "Prom1 deficiency in RPE triggers stress, inflammation, and partial EMT, leading to AMD-like degeneration.", "protein": "Prominin-1 (CD133)", "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "high", "disease": "Stargardt Disease Type 4 (STGD4)", "glycan_involvement": "Glycosylation may affect Prom1 stability and trafficking.", "mechanism": "Prom1 mutations (e.g., R373C) cause parafoveal RPE atrophy and photoreceptor loss.", "protein": "Prominin-1 (CD133)", "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "high", "disease": "Photoreceptor Degeneration", "glycan_involvement": "MerTK glycosylation required for receptor function.", "mechanism": "Reduced MerTK in Prom1-deficient RPE impairs phagocytosis of photoreceptor outer segments.", "protein": "MerTK", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological proce", "gene_name": "MERTK", "glycan_count": 28, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G62461SM", "G10486CT", "G11629QQ", "G37399XV", "G59626AS", "G65184UU", "G80920RR", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G56784JY", "G57888GL", "G62765YT", "G02815KT", "G23010ZW", "G02030ZB", "G10019LZ", "G12580WI", "G15169WU", "G22310AV", "G38663NM", "G52527GH", "G83460ZZ", "G84452RH", "G06356OH", "G29068FM", "G43417UB" ], "uniprot_id": "Q12866" }, "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "RPE Atrophy", "glycan_involvement": "Glycosylation may regulate PINK1 stability.", "mechanism": "Prom1 loss reduces PINK1, leading to defective mitophagy and RPE degeneration.", "protein": "PINK1", "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Secreted glycoprotein; glycosylation affects activity.", "mechanism": "Upregulated GREM1 in Prom1-KO RPE induces EMT and fibrotic remodeling.", "protein": "Gremlin-1 (GREM1)", "protein_enriched": { "function": "Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH fe", "gene_name": "GREM1", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G59626AS", "G70441OD", "G43417UB", "G49108TO" ], "uniprot_id": "O60565" }, "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "Inflammatory Retinal Disease", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Upregulated in Prom1-KO RPE, Serpine2 modulates neurotropic and anti-angiogenic responses.", "protein": "Serpine2", "protein_enriched": { "function": "Granzyme B inhibitor", "gene_name": "SERPINB9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50453" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "Atrophic Age-Related Macular Degeneration (aAMD)", "glycan_involvement": "Glycosylation essential for receptor function.", "mechanism": "Upregulated IL1R1 activates complement pathway and inflammation in RPE.", "protein": "IL1R1", "relationship_type": "biomarker", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "RPE Atrophy", "glycan_involvement": "Glycosylation affects IGFBP2 stability and IGF binding.", "mechanism": "Downregulation in Prom1-KO RPE removes IGF-1 modulation, promoting RPE degeneration.", "protein": "IGFBP2", "protein_enriched": { "function": "Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proli", "gene_name": "IGFBP2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "P18065" }, "relationship_type": "protective", "source_pmcid": "PMC12692251" }, { "confidence": "medium", "disease": "Geographic Atrophy", "glycan_involvement": "Glycosylation modulates tight junction assembly.", "mechanism": "Downregulation in Prom1-KO RPE disrupts tight junctions, contributing to barrier breakdown and atrophy.", "protein": "Cldn2", "protein_enriched": { "function": "Forms paracellular channels: polymerizes in tight junction strands with cation- and water-selective channels through the strands, conveying epithelial permeability in a process known as paracellular t", "gene_name": "CLDN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P57739" }, "relationship_type": "causal", "source_pmcid": "PMC12692251" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Changes in N-glycan structures modulate IgG activity and inflammation.", "mechanism": "Aberrant IgG glycosylation contributes to pathogenesis by altering immune effector functions.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692266" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered N-glycosylation patterns are detectable in cancer patients.", "mechanism": "IgG glycan profiles serve as diagnostic markers for cancer.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "medium", "disease": "Infectious diseases", "glycan_involvement": "Disease-specific changes in N-glycosylation are observed.", "mechanism": "IgG glycan profiles can indicate infection status.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Reduced galactosylation of IgG N-glycans is a marker of aging.", "mechanism": "Age-related decline in \u03b2-1,4-galactosyltransferase (GalT) concentration drives changes in IgG glycan profiles.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Inflammaging", "glycan_involvement": "Non-galactosylated IgG N-glycans increase with age, promoting inflammation.", "mechanism": "IgG glycans act as molecular effectors influencing chronic inflammation in aging.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692266" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Restoring galactosylation may mitigate aging effects.", "mechanism": "GalT enzyme concentration is a potential target to modulate age-related glycan changes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Specific N-glycan patterns correlate with disease severity.", "mechanism": "IgG glycan profiles are diagnostic for autoimmune disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "GalT activity is required for age-dependent glycosylation shifts.", "mechanism": "B-cell-specific ablation of GalT (B4GALT1) in mice abolishes age-related IgG glycan changes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692266" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Early reduction in galactosylation is a prognostic marker.", "mechanism": "Decrease in IgG galactosylation in middle age predicts longer lifespan.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Loss of galactose residues on N-glycans marks aging.", "mechanism": "Non-galactosylated glycopeptides are more common in older individuals.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692266" }, { "confidence": "high", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "Progranulin is a glycoprotein; glycosylation is required for its secretion and stability.", "mechanism": "Haploinsufficiency due to GRN loss-of-function mutations reduces progranulin levels, leading to neurodegeneration.", "protein": "Progranulin", "relationship_type": "causal", "source_pmcid": "PMC12692286" }, { "confidence": "high", "disease": "Neuronal ceroid lipofuscinosis type 11 (NCL11)", "glycan_involvement": "Glycosylation is essential for lysosomal targeting and function.", "mechanism": "Homozygous GRN mutations cause complete progranulin deficiency, resulting in lysosomal dysfunction.", "protein": "Progranulin", "relationship_type": "causal", "source_pmcid": "PMC12692286" }, { "confidence": "high", "disease": "Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP)", "glycan_involvement": "Glycosylation affects progranulin trafficking and lysosomal function.", "mechanism": "Reduced progranulin leads to TDP-43 proteinopathy and neurodegeneration.", "protein": "Progranulin", "relationship_type": "causal", "source_pmcid": "PMC12692286" }, { "confidence": "medium", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "NCAM1 is highly polysialylated; glycosylation modulates cell-cell interactions.", "mechanism": "NCAM1 is used as a marker in neural differentiation models of FTD.", "protein": "NCAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12692286" }, { "confidence": "medium", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "TRA-1-81 is a carbohydrate epitope; glycosylation is essential for its detection.", "mechanism": "TRA-1-81 epitope on PODXL is used as a pluripotency marker in iPSC models for FTD.", "protein": "Podocalyxin-like protein 1 (PODXL)", "relationship_type": "biomarker", "source_pmcid": "PMC12692286" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "BTLA is a glycoprotein; glycosylation may affect cell surface expression and ligand binding.", "mechanism": "BTLA-expressing memory B cells are increased after belimumab treatment and correlate with improved SLE disease activity; BTLA engagement attenuates BCR/BAFF signaling.", "protein": "BTLA", "relationship_type": "protective", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "HVEM glycosylation may regulate receptor-ligand interactions.", "mechanism": "HVEM high memory B cells increase after belimumab and are associated with improved disease activity; HVEM is the ligand for BTLA, mediating inhibitory signaling.", "protein": "HVEM", "relationship_type": "protective", "source_pmcid": "PMC12692296" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "BAFF is a glycoprotein; glycosylation may affect secretion and receptor binding.", "mechanism": "BAFF promotes survival and maturation of autoreactive B cells, contributing to SLE pathogenesis; belimumab neutralizes BAFF.", "protein": "BAFF", "relationship_type": "causal", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Lupus nephritis", "glycan_involvement": "BTLA glycosylation may influence cell surface stability.", "mechanism": "BTLA deletion in lupus mouse models exacerbates nephritis, suggesting a protective role.", "protein": "BTLA", "relationship_type": "protective", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Btk is glycosylated; glycosylation may affect kinase activity.", "mechanism": "BTLA engagement suppresses Btk phosphorylation, attenuating BCR/BAFF signaling in B cells, which may reduce SLE activity.", "protein": "Btk", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "PLC\u03b32 glycosylation may regulate enzyme function.", "mechanism": "BTLA engagement suppresses PLC\u03b32 phosphorylation downstream of BCR/BAFF signaling, reducing B cell activation.", "protein": "PLC\u03b32", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgG1 glycosylation affects effector function and immune complex formation.", "mechanism": "Serum IgG levels inversely correlate with BTLA high memory B cell frequency after belimumab, reflecting disease improvement.", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 glycosylation is essential for complement activation.", "mechanism": "Serum C4 levels positively correlate with BTLA high memory B cell frequency and HVEM high memory B cell frequency after belimumab.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Antibody glycosylation affects immune complex formation and pathogenicity.", "mechanism": "BTLA low naive B cell frequency positively correlates with anti-DNA antibody titers, indicating disease exacerbation.", "protein": "Anti-double stranded DNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12692296" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "NF-\u03baB2 is glycosylated; glycosylation may affect nuclear translocation.", "mechanism": "BTLA engagement inhibits BAFF-induced p100-to-p52 processing, suppressing non-canonical NF-\u03baB signaling in B cells.", "protein": "NF-\u03baB2 (p100/p52)", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q00653" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692296" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "O-glycosylation critical for mucus gel formation and barrier function.", "mechanism": "Upregulated in chronic inflammation; altered mucus barrier integrity.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692331" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Binds \u03b2-galactoside glycans on mucins and cell adhesion molecules.", "mechanism": "Upregulated in aged appendix; serum levels elevated in UC; modulates inflammation and fibrosis.", "protein": "Galectin-3 (LGALS3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentia", "gene_name": "LGALS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17931" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692331" }, { "confidence": "high", "disease": "Gut Barrier Dysfunction (Leaky Gut)", "glycan_involvement": "Glycosylation affects trafficking and stability of claudins.", "mechanism": "Upregulation loosens tight junctions, increases paracellular permeability.", "protein": "CLDN2", "relationship_type": "causal", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Neuronal Loss/Enteric Neuropathy", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Downregulation impairs neuronal survival and synaptic plasticity.", "protein": "NELL2", "relationship_type": "causal", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Carcinogenesis (Colorectal Cancer)", "glycan_involvement": "Secreted glycoprotein; glycosylation modulates stability and signaling.", "mechanism": "Overexpression promotes epithelial proliferation and is linked to cancer progression.", "protein": "REG4", "protein_enriched": { "function": "Calcium-independent lectin displaying mannose-binding specificity and able to maintain carbohydrate recognition activity in an acidic environment. May be involved in inflammatory and metaplastic respo", "gene_name": "REG4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BYZ8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Chronic Inflammation (Inflammaging)", "glycan_involvement": "Glycosylation affects secretion and protease inhibition.", "mechanism": "Upregulated in aged appendix; marker of goblet cell activity and mucosal repair.", "protein": "SPINK4", "relationship_type": "biomarker", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Impaired Intestinal Regeneration", "glycan_involvement": "O-glycosylation required for stability and mucosal healing.", "mechanism": "Upregulated with aging; promotes epithelial restitution and repair.", "protein": "TFF3", "relationship_type": "protective", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Intestinal Fibrosis", "glycan_involvement": "N-glycosylation modulates receptor binding and activity.", "mechanism": "Upregulated in aged appendix; drives epithelial proliferation and fibrotic remodeling.", "protein": "AREG", "relationship_type": "causal", "source_pmcid": "PMC12692331" }, { "confidence": "medium", "disease": "Neuronal Loss/Enteric Neuropathy", "glycan_involvement": "Polysialylation (N-glycan modification) regulates cell-cell interactions.", "mechanism": "Downregulation disrupts neuronal adhesion and synaptic stability.", "protein": "NCAM2", "protein_enriched": { "function": "Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting (PubMed:17646382). Sorting rec", "gene_name": "SORL1", "glycan_count": 99, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G00912UN", "G07246CJ", "G08290VR", "G08918WF", "G11870QZ", "G25418HZ", "G25451PN", "G27058EU", "G34989PA", "G37412TK", "G41071NU", "G43223CG", "G45395BF", "G47644PP", "G50856PC", "G57776ZS", "G59626AS", "G61256FT", "G62765YT", "G70232NH", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81263BG", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G92135MA", "G93718GY", "G96577RX", "G57321FI", "G29068FM", "G43417UB", "G04657PL", "G35253PZ", "G80920RR", "G83460ZZ", "G86182NS", "G95865ZB", "G53434XO", "G31852PQ", "G64409MC", "G83229XP", "G00406II", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G39188ZX", "G64527OM", "G70101JE", "G01485JJ", "G07755XJ", "G10488MI", "G14972EH", "G17208MA", "G42124LM", "G58954YZ", "G70619PT", "G87661QW", "G92551JA", "G94470IW", "G49108TO", "G41247ZX", "G34029GR", "G46503DX", "G48584BU", "G85677PP", "G96368MM", "G10486CT", "G00273SJ", "G05049YU", "G27915IV", "G95177YH", "G37692EO", "G37399XV", "G40926MX", "G45504EY", "G83646BJ", "G11314AS", "G49955PK", "G72790NZ", "G10819WX", "G27947YN", "G29545VG", "G44215PV", "G59324HL", "G60033FS", "G63980BQ", "G65184UU", "G85269DF", "G90734RJ", "G98611JV", "G06247RL", "G20706XG", "G43669FQ" ], "uniprot_id": "Q92673" }, "relationship_type": "causal", "source_pmcid": "PMC12692331" }, { "confidence": "high", "disease": "Dysbiosis", "glycan_involvement": "O-glycans serve as microbial substrates and modulate immune responses.", "mechanism": "Altered glycosylation and expression affect microbiota composition and host-microbe interactions.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC12692331" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation state affects inflammatory signaling.", "mechanism": "GlycA is elevated in obese individuals and pregnant women, associated with low-grade inflammation and insulin resistance.", "protein": "Alpha-1-acid glycoprotein (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC12692332" }, { "confidence": "high", "disease": "Pediatric obesity", "glycan_involvement": "Glycosylation required for hormone stability and receptor interaction.", "mechanism": "SCFA-induced GLP-1 secretion reduces appetite and increases energy expenditure.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Pediatric obesity", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "SCFA stimulation increases GLP-2, improving gut barrier and metabolic health.", "protein": "GLP-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Pediatric obesity", "glycan_involvement": "Glycosylation influences peptide stability.", "mechanism": "SCFA-induced PYY secretion decreases food intake.", "protein": "PYY", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692332" }, { "confidence": "high", "disease": "Pediatric obesity", "glycan_involvement": "Glycosylation essential for secretion and receptor binding.", "mechanism": "Leptin pathway stimulated by SCFA-GPR41 signaling, suppresses appetite.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "protective", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Pediatric obesity", "glycan_involvement": "Glycosylation affects hormone activity.", "mechanism": "Suppressed by butyrate-GLP-1 axis, reducing hunger signals.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "causal", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Indirect; HDAC activity can affect glycoprotein gene expression.", "mechanism": "SCFAs inhibit HDAC, modulating gene expression for metabolic regulation.", "protein": "Histone deacetylase (HDAC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692332" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect transporter function.", "mechanism": "Transports butyrate, influencing blood-brain barrier and metabolic signaling.", "protein": "SLC5A8", "relationship_type": "causal", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates peptide activity.", "mechanism": "Inhibited by leptin and GLP-1, reducing appetite.", "protein": "Neuropeptide Y (NPY)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692332" }, { "confidence": "medium", "disease": "Precocious puberty", "glycan_involvement": "Glycosylation affects peptide signaling.", "mechanism": "Microbiome regulates Kiss-1/GnRH pathway, linking obesity to early puberty.", "protein": "Kisspeptin (Kiss-1)", "relationship_type": "causal", "source_pmcid": "PMC12692332" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "P-glycoprotein is a heavily N-glycosylated membrane protein; glycosylation is essential for its stability and trafficking.", "mechanism": "Overexpression of P-glycoprotein leads to efflux of carfilzomib, causing resistance to therapy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Plasma Cell Leukemia", "glycan_involvement": "Glycosylation required for proper membrane localization and function.", "mechanism": "Elevated ABCB1 gene expression and P-gp protein levels are associated with aggressive plasma cell leukemia.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Chemotherapy Resistance", "glycan_involvement": "N-glycosylation affects substrate specificity and transporter activity.", "mechanism": "P-gp actively exports chemotherapeutic agents (e.g., carfilzomib, doxorubicin, paclitaxel) out of cells, reducing drug efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation status may influence inhibitor binding and efficacy.", "mechanism": "Inhibition of P-gp (e.g., with elacridar, ulixertinib, cobimetinib) restores sensitivity to carfilzomib in resistant MM cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation is necessary for cell surface expression and detection.", "mechanism": "High P-gp expression marks MM cells with acquired resistance to proteasome inhibitors.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for functional transporter; not directly regulated by MAPK but essential for activity.", "mechanism": "MAPK pathway activation (RAS/RAF/MEK/ERK) upregulates ABCB1/P-gp expression, promoting drug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may affect inhibitor access and transporter conformation.", "mechanism": "MEK and ERK inhibitors (cobimetinib, ulixertinib) suppress P-gp expression/function, reversing resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692345" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for mature, functional protein.", "mechanism": "NF-\u03baB, PI3K/Akt, and other pathways also implicated in ABCB1/P-gp upregulation and resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12692345" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for surface expression and detection.", "mechanism": "APE1/YB-1/ABCB1 gene signature (including P-gp) correlates with adverse outcomes in MM.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692345" }, { "confidence": "medium", "disease": "Chemotherapy Resistance", "glycan_involvement": "Glycosylation may affect drug binding and inhibition.", "mechanism": "Drug repurposing (e.g., HIV protease inhibitors) can inhibit P-gp and restore chemosensitivity.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692345" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "SR-BI is a glycoprotein; glycosylation may affect receptor-ligand interactions and liposome binding.", "mechanism": "SR-BI mediates CPX-351 uptake into leukemic blasts, enhancing drug delivery and cytotoxicity.", "protein": "SR-BI", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692354" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation influences apolipoprotein structure and interaction with SR-BI.", "mechanism": "Forms protein corona on CPX-351 liposomes, facilitating SR-BI-mediated uptake by AML cells.", "protein": "Apolipoprotein A-I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Glycosylation modulates apolipoprotein function and liposome interaction.", "mechanism": "Similar to ApoA-I, aids in protein corona formation and SR-BI-mediated liposome uptake.", "protein": "Apolipoprotein A-II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "CD33 glycosylation affects antibody binding and targeting efficiency.", "mechanism": "Liposomes can be functionalized with anti-CD33 antibodies for targeted AML cell delivery.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "N-glycosylation of transferrin modulates receptor binding and targeting.", "mechanism": "Transferrin-functionalized liposomes enhance selective drug delivery to AML cells.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692354" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation affects P-glycoprotein stability and drug transport function.", "mechanism": "P-glycoprotein mediates drug efflux, contributing to chemotherapy resistance in AML.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "causal", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Glycosylation may regulate hENT1 membrane localization and function.", "mechanism": "Downregulation of hENT1 is linked to cytarabine resistance; CPX-351 uptake is hENT1-independent.", "protein": "hENT1", "relationship_type": "biomarker", "source_pmcid": "PMC12692354" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation status may affect TP53 stability and activity.", "mechanism": "TP53 mutations predict poor response and survival with CPX-351 in AML.", "protein": "TP53", "relationship_type": "biomarker", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Potential glycosylation may modulate RUNX1 function.", "mechanism": "RUNX1 mutations are frequent in high-risk AML and may influence CPX-351 response.", "protein": "RUNX1", "protein_enriched": { "function": "Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3',", "gene_name": "RUNX1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q01196" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692354" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Glycosylation may affect ASXL1 protein interactions.", "mechanism": "ASXL1 mutations are common in adverse-risk AML and impact prognosis.", "protein": "ASXL1", "protein_enriched": { "function": "Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation", "gene_name": "UNK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9C0B0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692354" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Not directly addressed; BAG3 is a glycoprotein but glycosylation not discussed.", "mechanism": "Serum BAG3 levels correlate positively with fibrosis severity; reflects hepatocellular stress and fibrogenic burden.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not specified.", "mechanism": "Serum BAG3 is elevated in MASLD patients, especially with advanced disease.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Not specified.", "mechanism": "BAG3 levels are more than two-fold higher in cirrhosis/HCC compared to uncomplicated MASLD.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12692393" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not specified.", "mechanism": "BAG3 is elevated in MASLD-related HCC, reflecting advanced fibrotic remodeling.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12692393" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Not specified.", "mechanism": "BAG3 upregulation promotes hepatic stellate cell activation, apoptosis resistance, and extracellular matrix deposition.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "causal", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "TM6SF2 is a glycoprotein; glycosylation not discussed.", "mechanism": "TM6SF2 E167K variant increases hepatic lipid retention, ER stress, and indirectly upregulates BAG3, promoting fibrosis.", "protein": "TM6SF2 (Transmembrane 6 superfamily member 2)", "protein_enriched": { "function": "May play a role in preadipocyte differentiation and adipogenesis", "gene_name": "AAMDC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7C9" }, "relationship_type": "causal", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Possible glycoprotein; glycosylation not discussed.", "mechanism": "PNPLA3 I148M variant impairs triglyceride hydrolysis, leading to lipid accumulation, lipotoxicity, and fibrogenesis.", "protein": "PNPLA3 (Patatin-like phospholipase domain-containing protein 3)", "relationship_type": "causal", "source_pmcid": "PMC12692393" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Targeting BAG3 may modulate stress response and fibrogenic signaling in MASLD.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Not specified.", "mechanism": "BAG3 integrates genetic risk (PNPLA3, TM6SF2) and cellular stress, reflecting cumulative fibrogenic risk.", "protein": "BAG3 (Bcl-2-associated athanogene 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation not discussed.", "mechanism": "TM6SF2 E167K variant promotes hepatic steatosis and fibrosis via impaired VLDL secretion.", "protein": "TM6SF2 (Transmembrane 6 superfamily member 2)", "protein_enriched": { "function": "May play a role in preadipocyte differentiation and adipogenesis", "gene_name": "AAMDC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7C9" }, "relationship_type": "causal", "source_pmcid": "PMC12692393" }, { "confidence": "high", "disease": "Hepatic Fibrosis (MASLD/NAFLD)", "glycan_involvement": "AST and ALT are glycoproteins; altered glycosylation may affect their serum levels and activity.", "mechanism": "FIB-4 reflects early fibrotic remodeling in the liver, indicating hepatic stress in obesity.", "protein": "FIB-4 index (AST, ALT, Platelets)", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "medium", "disease": "Hepatic Fibrosis (MASLD/NAFLD)", "glycan_involvement": "N-glycosylation may modulate AST stability and clearance.", "mechanism": "Elevated AST is a component of FIB-4 and signals hepatocyte injury and fibrosis.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "medium", "disease": "Hepatic Fibrosis (MASLD/NAFLD)", "glycan_involvement": "N-glycosylation may affect ALT secretion and function.", "mechanism": "ALT elevation is used in FIB-4 and reflects hepatic injury.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "medium", "disease": "Hepatic Fibrosis (MASLD/NAFLD)", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion and inflammation; altered glycosylation may affect function.", "mechanism": "Platelet count is inversely related to fibrosis; platelets express glycoproteins involved in liver inflammation.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "high", "disease": "Microalbuminuria", "glycan_involvement": "N-glycosylation of albumin affects its filtration and reabsorption in the kidney.", "mechanism": "Elevated urinary albumin signals early renal involvement in metabolic syndrome.", "protein": "Urinary Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "CRP is N-glycosylated; glycan structure modulates its inflammatory activity.", "mechanism": "CRP is elevated in obesity and metabolic syndrome, reflecting low-grade inflammation.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "ApoA1 glycosylation affects HDL function and anti-inflammatory properties.", "mechanism": "Low HDL-C is associated with increased cardiovascular risk in obesity.", "protein": "HDL-associated glycoproteins (ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Albumin glycosylation influences glomerular filtration and CKD progression.", "mechanism": "eGFR decline signals early renal dysfunction in metabolic syndrome.", "protein": "eGFR (includes albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "low", "disease": "Hepatic Fibrosis (MASLD/NAFLD)", "glycan_involvement": "N-glycosylation pattern changes in liver disease.", "mechanism": "Altered transferrin glycosylation is associated with liver disease progression.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "low", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycan changes modulate immune response and inflammation.", "mechanism": "Altered immunoglobulin glycosylation reflects inflammatory status in obesity.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12692402" }, { "confidence": "high", "disease": "X-linked severe combined immunodeficiency (X-SCID)", "glycan_involvement": "\u03b3c is a glycoprotein; glycosylation is essential for receptor function and cell surface expression.", "mechanism": "Deficiency of \u03b3c impairs cytokine signaling, blocking T and NK cell development.", "protein": "Common \u03b3 chain (\u03b3c)", "protein_enriched": { "function": "Common subunit for the receptors for a variety of interleukins. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770)", "gene_name": "IL2RG", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P31785" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Wiskott\u2013Aldrich syndrome", "glycan_involvement": "WASp is glycosylated; glycosylation affects stability and function in immune cells.", "mechanism": "Mutations in WAS gene disrupt WASp, affecting hematopoietic cell signaling and cytoskeleton.", "protein": "Wiskott\u2013Aldrich syndrome protein (WASp)", "protein_enriched": { "function": "Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex (PubMed:12235133, PubMed:12769847, PubMed:16275905). Important for effici", "gene_name": "WAS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42768" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Adenosine deaminase deficiency (ADA-SCID)", "glycan_involvement": "ADA is a glycoprotein; glycosylation is required for secretion and activity.", "mechanism": "ADA deficiency leads to toxic metabolite accumulation, impairing lymphocyte development.", "protein": "Adenosine deaminase (ADA)", "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Cerebral adrenoleukodystrophy (CALD)", "glycan_involvement": "ALDP is glycosylated; glycosylation is important for peroxisomal targeting and function.", "mechanism": "Mutations in ABCD1 gene disrupt ALDP, causing accumulation of very long-chain fatty acids.", "protein": "Adrenoleukodystrophy protein (ALDP)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed", "gene_name": "ABCD1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P33897" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "\u03b2-thalassemia", "glycan_involvement": "\u03b2-globin is glycosylated; glycosylation affects hemoglobin assembly and stability.", "mechanism": "Mutations in HBB gene reduce or abolish \u03b2-globin production, causing anemia.", "protein": "\u03b2-globin", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBB", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G27391WQ", "G49108TO" ], "uniprot_id": "P68871" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Glycosylation may modulate hemoglobin solubility and aggregation.", "mechanism": "E6V mutation in HBB gene produces sickle hemoglobin, leading to erythrocyte deformation.", "protein": "\u03b2-globin", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBB", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G27391WQ", "G49108TO" ], "uniprot_id": "P68871" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "\u03b3-globin is glycosylated; glycosylation supports proper hemoglobin function.", "mechanism": "Increased \u03b3-globin (HbF) expression inhibits sickling and ameliorates disease severity.", "protein": "\u03b3-globin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Metachromatic leukodystrophy (MLD)", "glycan_involvement": "ARSA is a lysosomal glycoprotein; glycosylation is critical for enzyme activity and lysosomal targeting.", "mechanism": "ARSA deficiency leads to sulfatide accumulation, causing demyelination.", "protein": "Aryl sulfatase A (ARSA)", "protein_enriched": { "function": "Hydrolyzes cerebroside sulfate", "gene_name": "ARSA", "glycan_count": 29, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G51623PN", "G80966KZ", "G08011QI", "G82020ZR", "G82348BZ", "G84155GY", "G87597CN", "G96536XO", "G57321FI", "G00406II", "G01304XG", "G05724UK", "G06110VR", "G08790WV", "G10073SM", "G25637MV", "G32550BI", "G39188ZX", "G49447IS", "G51895WL", "G64527OM", "G66538GV", "G72282QM", "G74724QE", "G77852EK", "G81269JJ", "G83400DU", "G85121LW", "G93975QL" ], "uniprot_id": "P15289" }, "relationship_type": "causal", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "T cell acute lymphoblastic leukemia", "glycan_involvement": "LMO2 is a glycoprotein; glycosylation may affect nuclear localization and function.", "mechanism": "Insertional activation of LMO2 by viral vectors leads to oncogenesis in gene therapy.", "protein": "LMO2", "protein_enriched": { "function": "Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state", "gene_name": "LMO2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25791" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692421" }, { "confidence": "medium", "disease": "Myelodysplastic syndrome", "glycan_involvement": "PRDM16 is a glycoprotein; glycosylation may influence protein stability.", "mechanism": "Insertional activation of PRDM16 by lentiviral vectors is associated with hematological malignancy.", "protein": "PRDM16", "protein_enriched": { "function": "Binds DNA and functions as a transcriptional regulator (PubMed:12816872). Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). Proba", "gene_name": "PRDM16", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31370VX", "G49108TO" ], "uniprot_id": "Q9HAZ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692421" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Glycation and oxidation of Lp(a) enhance vascular inflammation and plaque instability.", "mechanism": "Promotes atherogenesis via intimal retention, inflammation, and antifibrinolysis.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692428" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "Glycation increases retention and inflammatory signaling in cerebral vessels.", "mechanism": "Elevated Lp(a) induces endothelial dysfunction, oxidative stress, and prothrombotic states.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692428" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "AGE-modified Lp(a) amplifies renal inflammation and fibrosis.", "mechanism": "Correlates with mesangial proliferation and glomerulosclerosis via PLC\u2013IP3\u2013Ca2+ signaling.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692428" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "Oxidized/glycated Lp(a) induces vascular leakage and retinal injury.", "mechanism": "Elevated Lp(a) and apo(a) levels associated with retinal capillary damage and inflammation.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692428" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "AGE-Lp(a) exacerbates endothelial dysfunction and nerve ischemia.", "mechanism": "Promotes vascular inflammation, inhibits fibrinolysis, and reduces neural perfusion.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692428" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation affects folding, secretion, and plasma levels of apo(a).", "mechanism": "Molecular mimicry with plasminogen inhibits fibrinolysis, increasing thrombosis risk.", "protein": "Apolipoprotein(a) [apo(a)]", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692428" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycation/oxidation of Lp(a) increases atherogenicity.", "mechanism": "Independent predictor of residual cardiovascular risk in diabetes.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692428" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "OxPL fraction of apo(a) induces macrophage apoptosis and retinal injury.", "mechanism": "Higher serum apo(a) levels correlate with retinopathy severity.", "protein": "Apolipoprotein(a) [apo(a)]", "relationship_type": "biomarker", "source_pmcid": "PMC12692428" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation state may affect renal handling and excretion.", "mechanism": "Elevated apo(a) fragments in urine reflect renal involvement and progression.", "protein": "Apolipoprotein(a) [apo(a)]", "relationship_type": "biomarker", "source_pmcid": "PMC12692428" }, { "confidence": "high", "disease": "Diabetes Mellitus (general)", "glycan_involvement": "Glycosylation impacts Lp(a) synthesis and plasma levels, influencing therapeutic response.", "mechanism": "RNA-based therapies targeting Lp(a) reduce risk of micro- and macrovascular complications.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692428" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Cell surface glycosylation mediates neutrophil adhesion and migration.", "mechanism": "Upregulated in CRC; reflects neutrophil activation and systemic inflammation.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Potential O-glycosylation may affect scaffold function and cell polarity.", "mechanism": "Altered expression in CRC; involved in epithelial integrity and inflammation.", "protein": "DLG5", "protein_enriched": { "function": "Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them", "gene_name": "DLG5", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "Q8TDM6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Possible glycosylation regulates immune adaptor activity.", "mechanism": "Differentially expressed; modulates NK/T-cell signaling in tumor\u2013host interactions.", "protein": "SH2D1B", "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Potential glycosylation may influence stability and activity.", "mechanism": "Upregulated in CRC; involved in redox homeostasis and oxidative stress response.", "protein": "NQO2", "protein_enriched": { "function": "The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitam", "gene_name": "NQO2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16083" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Keratin glycosylation may affect filament assembly and cell structure.", "mechanism": "Downregulated in CRC; reflects loss of epithelial differentiation and EMT.", "protein": "KRT73", "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation critical for cell surface localization and immune function.", "mechanism": "Marker of neutrophil activation in systemic inflammatory states.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation modulates IgG binding and immune signaling.", "mechanism": "Associated with immune cell infiltration in CRC.", "protein": "FCGR1A", "protein_enriched": { "function": "High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Mediates IgG effector functions on monocytes triggering antibody-dependent ce", "gene_name": "FCGR1A", "glycan_count": 39, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G01760ZU", "G03382KH", "G05724UK", "G06110VR", "G17689DH", "G22310AV", "G23432EQ", "G23863VK", "G25520XG", "G26915XM", "G29011JC", "G31916IQ", "G31936TA", "G39188ZX", "G39213VZ", "G46687AB", "G49874UX", "G55220VL", "G60145BJ", "G62326NX", "G62389NM", "G63381RX", "G64527OM", "G70418MS", "G72291OX", "G72667IM", "G72797UR", "G72902CL", "G74430RZ", "G78059CC", "G80858MF", "G82119TF", "G84452RH", "G90093AU", "G90717TP", "G91636VS", "G93141AZ", "G96095QD", "G96771UL" ], "uniprot_id": "P12314" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect antimicrobial activity.", "mechanism": "Stage-associated transcript; involved in innate immunity.", "protein": "DEFA4", "protein_enriched": { "function": "Host-defense peptide that has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi (PubMed:15317502, PubMed:15616305, PubMed:2500", "gene_name": "DEFA4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12838" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation required for enzymatic activity and stability.", "mechanism": "Stage-associated transcript; reflects neutrophil activity and oxidative stress.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "low", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation modulates secretion and protease activity.", "mechanism": "Differentially expressed; involved in extracellular matrix remodeling.", "protein": "ADAMTS1", "relationship_type": "biomarker", "source_pmcid": "PMC12692440" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Decreased serum albumin reflects urinary loss due to glomerular damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). 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Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)/MAFLD", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates its serum stability and tissue distribution.", "mechanism": "Elevated ALP correlates with hepatic steatosis and fibrosis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "GGT glycosylation affects its secretion and activity.", "mechanism": "Increased GGT indicates hepatobiliary injury or cholestasis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation status may influence renal handling of albumin.", "mechanism": "Decreased serum albumin can predict acute kidney injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation may affect ALP isoform distribution in serum.", "mechanism": "Serum ALP is associated with metabolic syndrome components.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Obesity may alter albumin glycosylation, affecting its function.", "mechanism": "Serum albumin may decrease in obesity-related inflammation or malnutrition.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation influences ALP activity and serum levels.", "mechanism": "ALP increases with obesity and high-fructose diets.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Inflammation may alter glycosylation of albumin.", "mechanism": "Low albumin is associated with systemic inflammation in metabolic syndrome.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)/MAFLD", "glycan_involvement": "Glycosylation modulates GGT serum activity.", "mechanism": "GGT elevation is linked to hepatic steatosis and oxidative stress.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692467" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Sclerostin is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Sclerostin inhibits bone formation by antagonizing Wnt signaling; lower sclerostin in Chrebp KO mice increases bone density.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "causal", "source_pmcid": "PMC12692475" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "IGF-1 is glycosylated; glycosylation affects bioactivity and half-life.", "mechanism": "Reduced IGF-1 expression in muscle (especially with insulin deficiency and Chrebp KO) leads to decreased muscle mass and strength.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12692475" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "OPG is glycosylated; glycosylation required for secretion and function.", "mechanism": "OPG inhibits RANKL-mediated osteoclast activation; reduced OPG in insulin-deficient Chrebp KO mice increases bone resorption.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "protective", "source_pmcid": "PMC12692475" }, { "confidence": "medium", "disease": "Muscle Atrophy", "glycan_involvement": "Myostatin is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Elevated myostatin in Chrebp KO and insulin-deficient states promotes muscle protein breakdown.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC12692475" }, { "confidence": "medium", "disease": "Bone Mineral Density Loss", "glycan_involvement": "BMP2 is glycosylated; glycosylation affects receptor binding.", "mechanism": "BMP2 promotes osteoblast differentiation; increased BMP2 in WT but not KO after STZ suggests impaired bone formation in KO.", "protein": "BMP2", "protein_enriched": { "function": "Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Ini", "gene_name": "Bmp2", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07036HW", "G80920RR", "G83633GK" ], "uniprot_id": "P21274" }, "relationship_type": "protective", "source_pmcid": "PMC12692475" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "RANKL is glycosylated; glycosylation modulates activity.", "mechanism": "RANKL promotes osteoclast differentiation and bone resorption; OPG acts as decoy receptor.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal", "source_pmcid": "PMC12692475" }, { "confidence": "high", "disease": "Bone Mineral Density Loss", "glycan_involvement": "Glycosylation required for sclerostin secretion.", "mechanism": "Sclerostin levels inversely correlate with bone density; lower in Chrebp KO, higher bone mass.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692475" }, { "confidence": "high", "disease": "Muscle Atrophy", "glycan_involvement": "Glycosylation affects IGF-1 stability.", "mechanism": "IGF-1 promotes muscle growth; reduced levels in insulin-deficient/Chrebp KO mice accelerate atrophy.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12692475" }, { "confidence": "high", "disease": "Bone Mineral Density Loss", "glycan_involvement": "Glycosylation required for OPG function.", "mechanism": "OPG reduction marks increased bone resorption and lower BMD in insulin-deficient/Chrebp KO mice.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692475" }, { "confidence": "medium", "disease": "Muscle Atrophy", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Atrogin-1 upregulation in muscle indicates increased protein degradation in insulin-deficient/Chrebp KO mice.", "protein": "Atrogin-1 (FBXO32)", "protein_enriched": { "function": "", "gene_name": "Ube-1c", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9R1R5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692475" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "ER\u03b2 expression correlates with Ki-67, indicating a proliferative role in TNBC.", "protein": "Estrogen Receptor Beta (ER\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC12692495" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "AR positivity is associated with more favorable disease-free interval, especially in ER\u03b2-positive TNBC.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692495" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "p53 positivity is associated with better prognosis in ER\u03b2-positive TNBC, possibly due to ER\u03b2 regulation of mutant p53.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692495" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "ER\u03b2 may interact with AR and p53, affecting response to antihormonal therapy.", "protein": "Estrogen Receptor Beta (ER\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692495" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "AR-targeted therapy is under clinical trial for AR-positive TNBC (luminal AR subtype).", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692495" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "ER\u03b2 forms heterodimers with AR, blocking AR proliferative signals and improving prognosis.", "protein": "Estrogen Receptor Beta (ER\u03b2)", "relationship_type": "protective", "source_pmcid": "PMC12692495" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "Mutant p53 promotes tumorigenesis; ER\u03b2 may regulate mutant p53 to reduce invasiveness.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "causal", "source_pmcid": "PMC12692495" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "Bcl-2-negative/p53-positive TNBC group has longer disease-free interval.", "protein": "Bcl-2", "relationship_type": "biomarker", "source_pmcid": "PMC12692495" }, { "confidence": "low", "disease": "Breast Cancer", "glycan_involvement": "Not specified in article.", "mechanism": "KLLN is AR-induced and promotes p53 expression, leading to apoptosis and cell cycle arrest.", "protein": "KLLN", "protein_enriched": { "function": "Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signal", "gene_name": "CSNK1A1L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N752" }, "relationship_type": "protective", "source_pmcid": "PMC12692495" }, { "confidence": "low", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Not specified in article.", "mechanism": "GPER is expressed in TNBC, but its role is unclear.", "protein": "G Protein-Coupled Estrogen Receptor (GPER)", "relationship_type": "biomarker", "source_pmcid": "PMC12692495" }, { "confidence": "high", "disease": "Non-Small-Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor stability.", "mechanism": "EGFR mutations drive oncogenic signaling; targeted by TKIs.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "ALK-rearranged NSCLC", "glycan_involvement": "N-glycosylation affects receptor folding and surface expression.", "mechanism": "ALK fusions cause constitutive kinase activation; targeted by ALK inhibitors.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "ROS1-rearranged NSCLC", "glycan_involvement": "N-glycosylation required for proper receptor function.", "mechanism": "ROS1 fusions activate oncogenic pathways; targeted by ROS1 inhibitors.", "protein": "ROS1", "protein_enriched": { "function": "Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous s", "gene_name": "ROS1", "glycan_count": 1, "glycosylation_sites_count": 30, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08922" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "HER2-positive NSCLC", "glycan_involvement": "N-glycosylation regulates receptor dimerization and signaling.", "mechanism": "HER2 overexpression/amplification drives tumor growth; targeted by ADCs and TKIs.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "METex14-mutant NSCLC", "glycan_involvement": "N-glycosylation influences receptor maturation and signaling.", "mechanism": "MET exon 14 skipping increases receptor stability; targeted by MET inhibitors.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "RET-fusion NSCLC", "glycan_involvement": "N-glycosylation required for cell surface localization.", "mechanism": "RET fusions activate kinase signaling; targeted by RET inhibitors.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "medium", "disease": "Non-Small-Cell Lung Cancer (NSCLC)", "glycan_involvement": "N- and O-glycosylation modulate cell adhesion and antibody binding.", "mechanism": "TROP-2 overexpression promotes tumor progression; targeted by ADCs.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "medium", "disease": "EGFR TKI-resistant NSCLC", "glycan_involvement": "N-glycosylation affects receptor interaction and stability.", "mechanism": "HER3 upregulation mediates resistance to EGFR TKIs; targeted by HER3-directed ADCs.", "protein": "HER3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "medium", "disease": "Pulmonary Sarcomatoid Carcinoma", "glycan_involvement": "N-glycosylation impacts receptor function.", "mechanism": "METex14 mutations are enriched in this subtype; guide MET inhibitor use.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692500" }, { "confidence": "medium", "disease": "Brain Metastases in NSCLC", "glycan_involvement": "N-glycosylation may affect blood-brain barrier crossing.", "mechanism": "EGFR mutations associated with CNS involvement; CNS-penetrant TKIs improve outcomes.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692500" }, { "confidence": "high", "disease": "SLC35A2-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Defective N-glycosylation (reduced galactosylation) of serum and cellular glycoproteins.", "mechanism": "Germline or systemic mosaic SLC35A2 variants impair UDP-galactose transport, causing global hypogalactosylation of glycoproteins.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "high", "disease": "MOGHE", "glycan_involvement": "Focal N-glycan hypogalactosylation in neurons and glia.", "mechanism": "Somatic brain-restricted SLC35A2 variants cause focal hypogalactosylation, leading to cortical malformation and epilepsy.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "high", "disease": "Early-Onset Epileptic Encephalopathy (EOEE)", "glycan_involvement": "Global N-glycan hypogalactosylation.", "mechanism": "De novo SLC35A2 mutations cause defective glycosylation, resulting in severe epilepsy and developmental delay.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "high", "disease": "Focal Cortical Dysplasia Type I (FCD1)", "glycan_involvement": "Focal N-glycan hypogalactosylation.", "mechanism": "Somatic SLC35A2 variants in cortex cause focal glycosylation defects, leading to FCD1 and epilepsy.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "medium", "disease": "Epilepsy (various forms)", "glycan_involvement": "Defective N-glycosylation of neuronal surface proteins.", "mechanism": "Altered N-glycosylation impairs folding/trafficking of ion channels and neurotransmitter receptors, contributing to epileptogenesis.", "protein": "N-glycosylated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "medium", "disease": "SLC35A2-CDG (Congenital Disorder of Glycosylation)", "glycan_involvement": "Impaired glycosphingolipid (ganglioside) galactosylation.", "mechanism": "SLC35A2 deficiency disrupts ganglioside biosynthesis, affecting neuronal membrane organization and signaling.", "protein": "Gangliosides", "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "medium", "disease": "MOGHE", "glycan_involvement": "Defective N- and O-glycosylation in oligodendrocytes.", "mechanism": "Focal SLC35A2 dysfunction leads to hypogalactosylation of myelin glycoproteins, contributing to oligodendroglial hyperplasia and network instability.", "protein": "Myelin-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "high", "disease": "Drug-resistant focal epilepsy", "glycan_involvement": "Focal N-glycan hypogalactosylation.", "mechanism": "Somatic SLC35A2 mutations in epileptogenic cortex cause local glycosylation defects, sustaining epileptogenic networks.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "medium", "disease": "Lennox\u2013Gastaut syndrome", "glycan_involvement": "Focal N-glycan hypogalactosylation.", "mechanism": "Somatic SLC35A2 variants in MOGHE patients are associated with Lennox\u2013Gastaut syndrome phenotype.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "causal", "source_pmcid": "PMC12692547" }, { "confidence": "medium", "disease": "MOGHE", "glycan_involvement": "Rescues N-glycan galactosylation in affected tissue.", "mechanism": "D-galactose supplementation increases UDP-galactose, partially restoring glycosylation and improving clinical outcomes.", "protein": "SLC35A2 (UDP-galactose transporter)", "protein_enriched": { "function": "Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-spec", "gene_name": "CYP2A13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16696" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692547" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may affect antigen processing and presentation.", "mechanism": "Autoantigen for autoreactive T cells; post-translationally modified insulin peptides (e.g., deamidated InsB:9\u201323) increase immunogenicity and drive beta-cell destruction.", "protein": "Insulin (INS)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may modulate epitope accessibility.", "mechanism": "Major autoantigen recognized by CD4+ T cells; deamidated forms are more immunogenic and correlate with disease progression.", "protein": "Glutamate decarboxylase 65 (GAD65)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Autoantigen targeted by both T and B cells; autoantibody presence predicts rapid progression.", "protein": "Islet antigen-2 (IA-2, PTPRN)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation status may influence immune recognition.", "mechanism": "Autoantigen; SNP (R325W) alters epitope immunogenicity and autoantibody response.", "protein": "Zinc transporter 8 (ZnT8, SLC30A8)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycopeptide nature may affect MHC presentation.", "mechanism": "Neoantigens formed by fusion of insulin fragments with other granule proteins; not present in thymus, leading to lack of central tolerance and strong T cell responses.", "protein": "Hybrid insulin peptides (HIPs)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Potential glycosylation may influence immunogenicity.", "mechanism": "Aberrant insulin translation products act as neoantigens, driving CD8+ T cell autoimmunity.", "protein": "Defective ribosomal insulin products (DRiPs)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may affect fusion peptide formation.", "mechanism": "Component of HIPs; acts as part of neoantigen recognized by autoreactive T cells.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation may affect peptide fusion and antigenicity.", "mechanism": "Forms HIPs with insulin C-peptide; recognized by diabetogenic T cell clones.", "protein": "Islet amyloid polypeptide (IAPP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Targeted by engineered TCR-Tregs (OTII-TCR) to suppress Th17 cells and reduce inflammation.", "protein": "SERPIN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation critical for antigenicity and immune response.", "mechanism": "Target for cross-reactive TCR-Tregs, enhancing immunoregulation in CNS autoimmunity.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692569" }, { "confidence": "medium", "disease": "Pathogen invasion (general)", "glycan_involvement": "Glycosylation increases viscosity and barrier function", "mechanism": "Physical barrier and possible inhibition of pathogen spore germination", "protein": "Mucilage glycoprotein (cactus pear)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "high", "disease": "Anthocyanin deficiency-related quality loss", "glycan_involvement": "Glycosylation may affect stability and activity of transcription factors", "mechanism": "Upregulation of anthocyanin biosynthesis under UV-B, improving fruit quality and stress resistance", "protein": "Anthocyanin biosynthesis regulatory glycoproteins (CaMYB113, CabHLH143, CaHY5)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Anthocyanin deficiency-related quality loss", "glycan_involvement": "Potential O-glycosylation modulates transcription factor activity", "mechanism": "UV-B upregulates FaMYB10, enhancing anthocyanin biosynthesis and fruit color", "protein": "FaMYB10 (strawberry)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Anthocyanin deficiency-related quality loss", "glycan_involvement": "Possible glycosylation affects nuclear localization and function", "mechanism": "Sensitive to UV-B, regulates early anthocyanin biosynthesis", "protein": "FaHY5 (strawberry)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Fusarium wilt", "glycan_involvement": "Glycosylation increases mucilage viscosity and pathogen resistance", "mechanism": "Barrier to soil-borne pathogen entry", "protein": "Root mucilage glycoprotein (general)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Powdery mildew", "glycan_involvement": "N-glycosylation enhances protein stability and cell wall integrity", "mechanism": "Strengthen cell wall against fungal penetration", "protein": "Cell wall glycoproteins (general)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Downy mildew", "glycan_involvement": "Glycosylation modulates cell wall protein function", "mechanism": "Cell wall reinforcement limits pathogen spread", "protein": "Cell wall glycoproteins (general)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Pest infestation (general)", "glycan_involvement": "Glycosylation affects regulatory protein activity", "mechanism": "Anthocyanin accumulation deters pests and enhances stress tolerance", "protein": "Anthocyanin biosynthesis regulatory glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Pest infestation (general)", "glycan_involvement": "Glycosylation increases mucilage effectiveness", "mechanism": "Physical barrier reduces pest feeding and oviposition", "protein": "Mucilage glycoprotein (cactus pear)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "medium", "disease": "Pathogen invasion (general)", "glycan_involvement": "N- and O-glycosylation critical for cell wall protein function", "mechanism": "Cell wall glycoproteins limit pathogen entry and spread", "protein": "Cell wall glycoproteins (general)", "relationship_type": "protective", "source_pmcid": "PMC12692572" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "LBP is a glycoprotein; glycosylation is required for secretion and function.", "mechanism": "LBP is elevated in MASLD and correlates with steatosis severity, reflecting increased intestinal permeability and endotoxemia.", "protein": "Lipopolysaccharide-binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "DAO is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "DAO is elevated in MASLD and correlates with steatosis severity, indicating intestinal epithelial damage.", "protein": "Diamine oxidase", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:12072962, PubMed:19764817, PubMed:239684, ", "gene_name": "AOC1", "glycan_count": 76, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G09831WQ", "G10486CT", "G11314AS", "G15664MX", "G23719VF", "G25079LO", "G28541PG", "G29184RN", "G29299MO", "G30221QT", "G31852PQ", "G37399XV", "G39446WN", "G40574BA", "G41247ZX", "G41840AI", "G46503DX", "G49018RC", "G49642SA", "G51653BI", "G57776ZU", "G59924QI", "G62765YT", "G72747WU", "G76295SF", "G80920RR", "G83460ZZ", "G90659AW", "G92406TI", "G96091TT", "G57321FI", "G29068FM", "G43417UB", "G00912UN", "G04657PL", "G07246CJ", "G07755XJ", "G08918WF", "G10819WX", "G14972EH", "G17208MA", "G27058EU", "G27126ED", "G27915IV", "G34989PA", "G37412TK", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49906RN", "G49955PK", "G57776ZS", "G59626AS", "G60033FS", "G65184UU", "G68490OW", "G70441OD", "G70619PT", "G72790NZ", "G79666IR", "G83646BJ", "G84225JN", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G90734RJ", "G94470IW", "G95177YH", "G49108TO" ], "uniprot_id": "P19801" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "DAO glycosylation may affect serum half-life.", "mechanism": "DAO levels decrease in advanced fibrosis, possibly reflecting loss of functional enterocytes.", "protein": "Diamine oxidase", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:12072962, PubMed:19764817, PubMed:239684, ", "gene_name": "AOC1", "glycan_count": 76, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G09831WQ", "G10486CT", "G11314AS", "G15664MX", "G23719VF", "G25079LO", "G28541PG", "G29184RN", "G29299MO", "G30221QT", "G31852PQ", "G37399XV", "G39446WN", "G40574BA", "G41247ZX", "G41840AI", "G46503DX", "G49018RC", "G49642SA", "G51653BI", "G57776ZU", "G59924QI", "G62765YT", "G72747WU", "G76295SF", "G80920RR", "G83460ZZ", "G90659AW", "G92406TI", "G96091TT", "G57321FI", "G29068FM", "G43417UB", "G00912UN", "G04657PL", "G07246CJ", "G07755XJ", "G08918WF", "G10819WX", "G14972EH", "G17208MA", "G27058EU", "G27126ED", "G27915IV", "G34989PA", "G37412TK", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G49906RN", "G49955PK", "G57776ZS", "G59626AS", "G60033FS", "G65184UU", "G68490OW", "G70441OD", "G70619PT", "G72790NZ", "G79666IR", "G83646BJ", "G84225JN", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G90734RJ", "G94470IW", "G95177YH", "G49108TO" ], "uniprot_id": "P19801" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "miR-122 regulates expression of glycoproteins involved in liver function.", "mechanism": "Serum miR-122 is elevated in MASLD and predicts disease presence and fibrosis progression.", "protein": "miR-122", "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "miR-21 regulates tight junction glycoproteins (e.g., occludin, claudins).", "mechanism": "Reduced serum miR-21 is an independent predictor of MASLD.", "protein": "miR-21", "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Zonulin is a glycoprotein; glycosylation may affect function.", "mechanism": "Elevated zonulin is associated with increased intestinal permeability.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Claudin-1 is glycosylated; glycosylation affects tight junction assembly.", "mechanism": "miR-29a downregulates claudin-1, contributing to barrier dysfunction.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "causal", "source_pmcid": "PMC12692580" }, { "confidence": "medium", "disease": "Irritable bowel syndrome", "glycan_involvement": "Indirect; targets glycoproteins involved in tight junctions.", "mechanism": "miR-29a upregulation correlates with increased intestinal permeability via downregulation of ZO-1 and claudin-1.", "protein": "miR-29a", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692580" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects receptor binding.", "mechanism": "TNF-\u03b1 is associated with inflammation in MASLD but not independently predictive in this study.", "protein": "Tumor necrosis factor alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "IL-6 is glycosylated; glycosylation modulates activity.", "mechanism": "IL-6 is involved in inflammation and fibrosis but not significantly altered in MASLD in this study.", "protein": "Interleukin 6", "relationship_type": "biomarker", "source_pmcid": "PMC12692580" }, { "confidence": "high", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "PD-1 is N-glycosylated, which affects its cell surface stability and ligand binding.", "mechanism": "Upregulated PD-1 expression on T cells indicates dominant T cell activation and immune dysregulation.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "PD-L1 N-glycosylation modulates its stability and immune inhibitory function.", "mechanism": "Increased PD-L1 expression on T and NK cells correlates with humoral immune predominance and autoantibody production.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "CTLA-4 N-glycosylation is essential for proper folding and surface expression.", "mechanism": "Elevated CTLA-4 expression on T cells reflects enhanced Treg-mediated suppression and checkpoint activation.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692590" }, { "confidence": "medium", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "CD86 is N-glycosylated, influencing ligand interactions and immune modulation.", "mechanism": "Higher CD86 transcript levels in MN PBMCs suggest increased costimulatory signaling and B cell activation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "CD200 N-glycosylation affects receptor binding and immunosuppressive function.", "mechanism": "Upregulation of CD200/CD200R axis may suppress inflammatory cytokine milieu and protect podocytes.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12692590" }, { "confidence": "medium", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "CD200R glycosylation modulates receptor signaling and immune inhibition.", "mechanism": "Attenuation of CD200/CD200R axis in MN is associated with increased proteinuria and reduced immune tolerance.", "protein": "CD200R", "relationship_type": "biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "Soluble PD-1 retains glycosylation, affecting its stability in circulation.", "mechanism": "Elevated serum soluble PD-1 differentiates MCD from MN and healthy controls.", "protein": "sPD-1", "relationship_type": "biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "Glycosylation of sPD-L1 influences its immunosuppressive activity.", "mechanism": "Serum sPD-L1 is increased in MN, reflecting checkpoint activation and disease activity.", "protein": "sPD-L1", "relationship_type": "biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "PLA2R is heavily N-glycosylated, which may affect antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against PLA2R drive subepithelial immune complex formation and podocyte injury.", "protein": "PLA2R", "protein_enriched": { "function": "Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response (PubMed:10066756, PubMed:16371369, PubMed:17090529, Pu", "gene_name": "PLA2G7", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q13093" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "medium", "disease": "Membranous Nephropathy (MN)", "glycan_involvement": "THSD7A glycosylation may modulate epitope exposure and immune recognition.", "mechanism": "Autoantibodies against THSD7A contribute to MN pathogenesis via immune complex deposition.", "protein": "THSD7A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692590" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Aberrant glycosylation enhances tumor cell adhesion and immune evasion.", "mechanism": "Elevated MUC1 mRNA in CTCs correlates with reduced survival and aggressive tumor biology.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "high", "disease": "Metastatic NSCLC", "glycan_involvement": "Glycosylation modulates cell adhesion and metastatic potential.", "mechanism": "Persistent CEACAM5 mRNA positivity in CTCs before/after therapy correlates with decreased PFS and OS.", "protein": "CEACAM5", "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation required for folate binding and cell surface expression.", "mechanism": "Preoperative FR+ CTC levels predict survival outcomes in NSCLC surgical patients.", "protein": "Folate Receptor Alpha (FR-\u03b1)", "protein_enriched": { "function": "A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated p", "gene_name": "ACP3", "glycan_count": 26, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G80858MF", "G15486FH", "G34442SS", "G39188ZX", "G41247ZX", "G46687AB", "G80475RE", "G81315DD", "G00912UN", "G06247RL", "G06356OH", "G08293MJ", "G10486CT", "G22310AV", "G27947YN", "G32926LW", "G48414YA", "G59626AS", "G67031OU", "G80223IX", "G85144OK", "G86752LQ", "G88374WZ", "G91158SA", "G94917XT" ], "uniprot_id": "P15309" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "N-glycosylation affects receptor stability and ligand binding.", "mechanism": "EGFR mutations and expression on CTCs guide targeted therapy and predict recurrence.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692596" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation modulates receptor activation and downstream signaling.", "mechanism": "High MET expression in CTCs linked to prognosis and EMT status.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "medium", "disease": "SCLC", "glycan_involvement": "Glycosylation regulates cell\u2013cell adhesion and EMT.", "mechanism": "Low E-cadherin expression in CTCs correlates with favorable prognosis in SCLC.", "protein": "E-cadherin (CDH1)", "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and modulates immune checkpoint activity.", "mechanism": "PD-L1+ CTCs associate with poor OS and predict immunotherapy response.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation influences cell adhesion and CTC detection.", "mechanism": "EpCAM mRNA-positive CTCs linked to shorter DFS and OS.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "medium", "disease": "SCLC", "glycan_involvement": "Glycosylation required for Notch ligand function.", "mechanism": "DLL3 mRNA/protein in CTCs correlates with poor OS in SCLC.", "protein": "DLL3", "protein_enriched": { "function": "One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell", "gene_name": "GJB5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95377" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation essential for folate binding and receptor trafficking.", "mechanism": "FR mRNA expression in CTCs predicts survival outcomes.", "protein": "FR", "relationship_type": "biomarker", "source_pmcid": "PMC12692596" }, { "confidence": "high", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation critical for secretion and function.", "mechanism": "Promotes insulin resistance and hepatic lipid accumulation, exacerbating MASLD progression.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692600" }, { "confidence": "high", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation required for stability and secretion.", "mechanism": "Increases fatty acid oxidation, reduces steatosis and inflammation; elevated in MASLD as compensatory response.", "protein": "FGF-21", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12692600" }, { "confidence": "high", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "O-glycosylation modulates multimerization and activity.", "mechanism": "Activates AMPK/PPAR-\u03b1, reduces hepatic steatosis, inflammation, and fibrosis; levels decline as MASLD progresses.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation essential for stability and receptor binding.", "mechanism": "Modulates insulin sensitivity, may reduce liver steatosis.", "protein": "Erythropoietin", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12692600" }, { "confidence": "high", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "O-glycosylation and phosphorylation regulate function.", "mechanism": "Promotes hepatic inflammation and fibrosis; elevated in MASLD/NASH.", "protein": "Osteopontin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation affects secretion and lipid binding.", "mechanism": "Impairs lipid clearance, associated with dyslipidemia and steatosis.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Elevated levels associated with increased risk of MASLD, obesity, and type 2 diabetes.", "protein": "RBP4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Anti-inflammatory and antioxidant properties; protective effect in MASLD.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "N-glycosylation modulates secretion and activity.", "mechanism": "Correlates with severity of liver injury; may reduce obesity-induced glucose intolerance.", "protein": "NGAL (Lipocalin-2)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12692600" }, { "confidence": "medium", "disease": "MASLD (Metabolic dysfunction-associated steatotic liver disease)", "glycan_involvement": "O-glycosylation may affect stability and secretion.", "mechanism": "Reduces steatosis, increases insulin release, reduces fibrosis via Nrf2 pathway.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12692600" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ERK2 dimerization drives oncogenic transformation and cell migration; inhibition curtails tumor progression.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692606" }, { "confidence": "high", "disease": "Metastatic cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ERK2 dimerization is necessary and sufficient for metastatic dissemination via cytoskeletal remodeling.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "causal", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Aberrant ERK2 dimerization promotes excessive immune cell and fibroblast migration, contributing to tissue remodeling.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "causal", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Metastatic cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "High KSR1 expression correlates with adverse metastatic features by facilitating ERK2 dimerization.", "protein": "KSR1 (Kinase suppressor of Ras 1)", "protein_enriched": { "function": "Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MA", "gene_name": "KSR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IVT5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Anaplastic thyroid cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ERK2 dimerization inhibition (by DEL-22379) impairs tumor growth in BRAF-mutant thyroid cancer.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Memory disorders (impaired reconsolidation/synaptic plasticity)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ERK2 dimerization is required for hippocampal memory reconsolidation and synaptic plasticity.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "causal", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "ERK2 dimerization activates cytoplasmic substrates like RSK1, promoting cell motility and tumor progression.", "protein": "RSK1 (Ribosomal S6 Kinase 1)", "protein_enriched": { "function": "Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and", "gene_name": "RPS6KA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15418" }, "relationship_type": "causal", "source_pmcid": "PMC12692606" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Small molecule inhibitors (DEL-22379, Drug73, Drug120) selectively block ERK2 dimerization, reducing tumor cell migration.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692606" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Targeting ERK2 dimerization interface (activation loop, leucine zipper) is effective for selective cancer therapy.", "protein": "ERK2 (Extracellular signal-regulated kinase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692606" }, { "confidence": "medium", "disease": "Metastatic cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "KSR1 scaffolding promotes ERK2 dimerization, driving EMT-like reprogramming and invasion.", "protein": "KSR1 (Kinase suppressor of Ras 1)", "protein_enriched": { "function": "Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MA", "gene_name": "KSR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IVT5" }, "relationship_type": "causal", "source_pmcid": "PMC12692606" }, { "confidence": "high", "disease": "H1N1 Influenza", "glycan_involvement": "HA is heavily glycosylated; glycan structures modulate host cell binding and immune evasion.", "mechanism": "HA mediates viral entry by binding to sialic acid on host cells.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692646" }, { "confidence": "high", "disease": "H1N1 Influenza", "glycan_involvement": "NA is glycosylated; glycan sites affect enzymatic activity and inhibitor binding.", "mechanism": "NA cleaves sialic acid to facilitate viral release; inhibition reduces viral spread.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "Acute Lung Injury", "glycan_involvement": "ACE2 glycosylation affects receptor stability and viral interactions.", "mechanism": "ACE2 downregulation by influenza infection contributes to lung injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "H1N1 Influenza", "glycan_involvement": "CD4 glycosylation modulates T cell activation and trafficking.", "mechanism": "CD4+ T cells orchestrate adaptive immune response; depletion worsens infection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "H1N1 Influenza", "glycan_involvement": "CD8 glycosylation influences cytotoxic function.", "mechanism": "CD8+ cytotoxic T cells eliminate infected cells; restoration improves outcomes.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "protective", "source_pmcid": "PMC12692646" }, { "confidence": "high", "disease": "H1N1 Influenza", "glycan_involvement": "Glycosylation affects cytokine stability and receptor binding.", "mechanism": "Elevated IFN-\u03b3 indicates immune activation and inflammation.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12692646" }, { "confidence": "high", "disease": "H1N1 Influenza", "glycan_involvement": "Glycosylation modulates cytokine secretion and activity.", "mechanism": "High IL-6 correlates with disease severity and inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692646" }, { "confidence": "high", "disease": "H1N1 Influenza", "glycan_involvement": "Glycosylation impacts cytokine function and receptor interactions.", "mechanism": "Elevated TNF-\u03b1 is associated with severe inflammation and poor prognosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "H1N1 Influenza", "glycan_involvement": "Glycosylation regulates NK cell receptor function.", "mechanism": "NK cells provide early defense by killing infected cells; restoration aids recovery.", "protein": "NK1.1 (NKR-P1B)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1A4" }, "relationship_type": "protective", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "H1N1 Influenza", "glycan_involvement": "N-glycosylation is essential for proper folding and antigen presentation.", "mechanism": "MHC I presents viral antigens to CD8+ T cells, enabling cytotoxic response.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12692646" }, { "confidence": "medium", "disease": "Diabetic Neuropathy (DN)", "glycan_involvement": "Glycosylation affects function of sweat gland proteins; altered glycosylation may impair nerve-skin interactions.", "mechanism": "Reduced electrochemical conductance of sweat (reflecting glycoprotein dysfunction in sweat glands) is used as a biomarker for small-fiber neuropathy in DN.", "protein": "SUDOSCAN-measured sweat gland glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692654" }, { "confidence": "high", "disease": "Balance Impairment", "glycan_involvement": "No direct link between glycosylation of these proteins and balance impairment established.", "mechanism": "Sudomotor dysfunction (small-fiber glycoprotein impairment) was NOT associated with balance impairment in T2DM patients.", "protein": "SUDOSCAN-measured sweat gland glycoproteins", "relationship_type": "biomarker (negative finding)", "source_pmcid": "PMC12692654" }, { "confidence": "high", "disease": "Fear of Falling", "glycan_involvement": "No direct link between glycosylation and psychological outcomes.", "mechanism": "Sudomotor dysfunction was NOT associated with increased fear of falling.", "protein": "SUDOSCAN-measured sweat gland glycoproteins", "relationship_type": "biomarker (negative finding)", "source_pmcid": "PMC12692654" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "CD74 is a glycoprotein; glycosylation supports its membrane localization and endocytic capacity, critical for ADC uptake.", "mechanism": "CD74 is highly expressed on B cells, dendritic cells, and macrophages, which drive SLE pathogenesis; targeting CD74 enables selective delivery of immunosuppressive drugs to these cells.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation of CD74 facilitates its function and ADC-mediated drug delivery.", "mechanism": "CD74-targeted Bud-ADC reduces renal IgG deposition and kidney damage in SLE models.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "medium", "disease": "Chronic Inflammatory Diseases", "glycan_involvement": "Glycosylation maintains CD74 structure and cell surface expression.", "mechanism": "CD74-targeted ADCs (with glucocorticoid payloads) show potential for broad immunosuppression in chronic inflammation.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "medium", "disease": "Chronic Inflammatory Diseases", "glycan_involvement": "E-selectin is a glycoprotein; glycosylation is essential for ligand binding and cell trafficking.", "mechanism": "E-selectin-targeted ADCs deliver dexamethasone to activated endothelial cells, reducing inflammation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "medium", "disease": "Chronic Inflammatory Diseases", "glycan_involvement": "TNF\u03b1 glycosylation affects secretion and receptor interaction.", "mechanism": "TNF\u03b1-targeted ADCs deliver glucocorticoids to TNF\u03b1-expressing cells, suppressing inflammation.", "protein": "TNF\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "medium", "disease": "Autoimmune Diseases", "glycan_involvement": "CD70 glycosylation supports cell surface expression and immune modulation.", "mechanism": "CD70-targeted ADCs deliver immunosuppressive drugs to CD70-expressing immune cells.", "protein": "CD70", "protein_enriched": { "function": "Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells (PubMed:28011863, PubMed:28011864, PubMed:8387892). The CD7", "gene_name": "CD70", "glycan_count": 16, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G06247RL", "G08918WF", "G27058EU", "G29299MO", "G40574BA", "G45395BF", "G57776ZS", "G63041LO", "G69521XL", "G79666IR", "G41247ZX", "G57321FI", "G49108TO" ], "uniprot_id": "P32970" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "medium", "disease": "Autoimmune Diseases", "glycan_involvement": "PRLR glycosylation is important for receptor function.", "mechanism": "PRLR-targeted ADCs deliver glucocorticoids to PRLR-expressing cells, modulating immune responses.", "protein": "PRLR", "protein_enriched": { "function": "This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and st", "gene_name": "PRLR", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P16471" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "BLyS glycosylation affects its stability and receptor binding.", "mechanism": "BLyS blockade (e.g., by Telitacicept) suppresses aberrant B cell function in SLE.", "protein": "BLyS (BAFF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "APRIL glycosylation modulates its activity and immune signaling.", "mechanism": "APRIL blockade (e.g., by Telitacicept) inhibits B cell activation and autoantibody production in SLE.", "protein": "APRIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692655" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "IgG glycosylation affects effector function and immune complex formation.", "mechanism": "Elevated autoantibody (IgG) levels are a hallmark of SLE; Bud-ADC reduces serum IgG and autoantibody titers.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692655" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation required for ENG function and release.", "mechanism": "Elevated sEng from hypoxic placenta inhibits TGF-\u03b2 signaling, impairs vascular integrity, correlates with disease severity.", "protein": "Endoglin (ENG/sEng)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692674" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation critical for ligand binding and stability.", "mechanism": "Placental sFlt1 overproduction antagonizes VEGF/PlGF, causing endothelial dysfunction.", "protein": "Soluble fms-like tyrosine kinase-1 (sFlt1/sVEGFR1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692674" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "N-glycosylation modulates secretion and receptor interaction.", "mechanism": "Reduced PlGF and altered sFlt1/PlGF ratio predict PE; PlGF supports angiogenesis.", "protein": "Placental Growth Factor (PlGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12692674" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "N-glycosylation affects VEGFA bioactivity.", "mechanism": "Impaired VEGFA signaling leads to defective angiogenesis and placental hypoperfusion.", "protein": "Vascular Endothelial Growth Factor A (VEGFA)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "Envelope glycoprotein; glycosylation required for fusogenic activity.", "mechanism": "Reduced Syncytin-1 impairs trophoblast fusion, EMT, and immune evasion.", "protein": "Syncytin-1", "relationship_type": "causal", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "N-glycosylation modulates cell adhesion properties.", "mechanism": "Elevated E-cadherin impairs trophoblast EMT, reducing invasion.", "protein": "E-cadherin (CDH1)", "relationship_type": "causal", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "Proteoglycan core with glycosaminoglycan chains essential for function.", "mechanism": "DCN inhibits trophoblast proliferation, migration, and invasion.", "protein": "Decorin (DCN)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Downregulated GLUT1 reduces placental glucose uptake, impairing trophoblast syncytialization.", "protein": "Glucose transporter 1 (GLUT1/SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "Downregulated ETBR impairs angiogenesis; circRNA/miRNA axes regulate ETBR in PE.", "protein": "Endothelin B Receptor (ETBR)", "protein_enriched": { "function": "Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system", "gene_name": "EDNRB", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P24530" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12692674" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "Reduced MMP2 impairs trophoblast invasion and vascular remodeling.", "protein": "Matrix Metalloproteinase 2 (MMP2)", "relationship_type": "causal", "source_pmcid": "PMC12692674" }, { "confidence": "high", "disease": "Progressive multiple sclerosis (PMS)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Beta-synuclein is released from damaged neurons, presented on HLA-DRB1*15:01, and is immunogenic in PMS; targeting it with Treg therapy may suppress inflammation and promote neural healing.", "protein": "Beta-synuclein", "protein_enriched": { "function": "Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated ", "gene_name": "SNCB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16143" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692681" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Elevated plasma/CSF beta-synuclein reflects synaptic damage and may serve as a biomarker for neurodegeneration in MS.", "protein": "Beta-synuclein", "protein_enriched": { "function": "Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated ", "gene_name": "SNCB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16143" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692681" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Beta-synuclein inhibits alpha-synuclein aggregation, potentially reducing synucleinopathy pathology.", "protein": "Beta-synuclein", "protein_enriched": { "function": "Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated ", "gene_name": "SNCB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16143" }, "relationship_type": "protective", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Alpha-synuclein aggregation is central to synucleinopathy pathogenesis.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC12692681" }, { "confidence": "medium", "disease": "Lewy body dementia", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Beta-synuclein aggregates found in brain tissue of patients; mutations may predispose to disease.", "protein": "Beta-synuclein", "protein_enriched": { "function": "Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated ", "gene_name": "SNCB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16143" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "MOG is a target autoantigen in MS; immune response against MOG contributes to demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "MBP is a target autoantigen in MS; immune response against MBP contributes to demyelination.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "causal", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "PLP is a target autoantigen in MS; immune response against PLP contributes to demyelination.", "protein": "Proteolipid protein (PLP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding and function.", "mechanism": "CD20 is targeted by ocrelizumab to deplete B cells, reducing inflammation in MS.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "HLA-DRB1*15:01 is a glycoprotein; glycosylation affects peptide presentation and immune recognition.", "mechanism": "HLA-DRB1*15:01 presents self-antigens (including beta-synuclein) to T cells, promoting autoimmunity in MS.", "protein": "HLA-DRB1*15:01", "relationship_type": "causal", "source_pmcid": "PMC12692681" }, { "confidence": "high", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N-glycosylation critical for ECM function and cell signaling.", "mechanism": "Promotes cell adhesion, migration, and invasion; downregulated by miR-21-targeted ASO reduces tumor aggressiveness.", "protein": "LAMC1", "relationship_type": "causal", "source_pmcid": "PMC12692703" }, { "confidence": "high", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N-glycosylation modulates cell\u2013matrix interactions.", "mechanism": "Facilitates ECM attachment and tumor cell motility; downregulation impairs migration.", "protein": "LAMB1", "relationship_type": "causal", "source_pmcid": "PMC12692703" }, { "confidence": "high", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N-glycosylation required for integrin function.", "mechanism": "Mediates cell\u2013ECM adhesion; altered by miR-21/Combi ASO reduces migration.", "protein": "ITGA1", "protein_enriched": { "function": "Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake (PubMed:10829012, PubMed:3", "gene_name": "GFRA1", "glycan_count": 14, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G57321FI", "G02628JF", "G08110WX", "G11911BT", "G45395BF", "G46524LG", "G56284ZY", "G62765YT", "G70232NH", "G81198YO", "G82592ZH", "G99966GV", "G49108TO" ], "uniprot_id": "P56159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "high", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N-glycosylation affects ligand binding.", "mechanism": "Regulates cell adhesion and migration; targeted by miR-21/Combi ASO.", "protein": "ITGA2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "medium", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N-glycosylation modulates integrin activity.", "mechanism": "Involved in cell migration and invasion; altered by miR-21/Combi ASO.", "protein": "ITGAV", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "high", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "N- and O-glycosylation regulate ECM assembly.", "mechanism": "Key ECM glycoprotein promoting tumor cell migration; downregulated by miR-21 ASO.", "protein": "FN1", "relationship_type": "causal", "source_pmcid": "PMC12692703" }, { "confidence": "medium", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "O-glycosylation implicated in nuclear pore function.", "mechanism": "Controls mitotic spindle assembly and nucleocytoplasmic transport; altered by miR-17/Combi ASO.", "protein": "NUP98", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "medium", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "O-glycosylation affects nuclear transport.", "mechanism": "Regulates nuclear pore complex and mitosis; altered by miR-17/Combi ASO.", "protein": "NUP107", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "medium", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "O-glycosylation modulates pore function.", "mechanism": "Involved in nuclear pore complex assembly; altered by miR-17 ASO.", "protein": "NUP85", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "medium", "disease": "Colorectal adenocarcinoma", "glycan_involvement": "O-glycosylation involved in nuclear transport.", "mechanism": "Essential for nuclear pore complex and mitosis; altered by miR-17/Combi ASO.", "protein": "NUP160", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692703" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "TLR2 is N-glycosylated, which is essential for ligand recognition and signaling.", "mechanism": "TLR2 activation increases KLK5 and LL-37, driving inflammation via mTOR signaling.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Ocular rosacea", "glycan_involvement": "TLR4 N-glycosylation modulates receptor trafficking and function.", "mechanism": "TLR4 overexpression amplifies oxidative stress and barrier damage in conjunctival epithelium.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "TLR7 glycosylation affects endosomal localization and signaling.", "mechanism": "TLR7 overexpression activates NF-\u03baB/mTORC1, increasing cytokine/chemokine production and T-cell migration.", "protein": "TLR7", "relationship_type": "causal", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "NF-\u03baB activity is modulated by upstream glycoprotein receptors (e.g., TLRs).", "mechanism": "NF-\u03baB activation drives chronic inflammation in skin and eyelid tissue.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "STAT3 signaling is downstream of glycoprotein cytokine receptors.", "mechanism": "STAT3 upregulation links skin barrier dysfunction to immune infiltration and inflammation.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "LL-37 is processed from glycosylated precursor hCAP18.", "mechanism": "LL-37 fragments generated by KLK5 promote inflammation and angiogenesis.", "protein": "LL-37 (cathelicidin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "MMP-9 is N-glycosylated, affecting secretion and activity.", "mechanism": "MMP-9 is elevated in skin, serum, tears, and gingival fluid, reflecting tissue remodeling and inflammation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "IDO is a glycoprotein enzyme; glycosylation affects stability and secretion.", "mechanism": "IDO is elevated in serum, indicating systemic immune activation.", "protein": "IDO", "relationship_type": "biomarker", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "IL-1\u03b2 is glycosylated, influencing secretion and receptor binding.", "mechanism": "IL-1\u03b2 is upregulated in lesional skin, driving MAPK and TNF pathways.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Rosacea", "glycan_involvement": "IL-6 N-glycosylation modulates receptor interaction and bioactivity.", "mechanism": "IL-6 is elevated in serum and lesional skin, promoting inflammation and angiogenesis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692705" }, { "confidence": "high", "disease": "Neovascular Age-related Macular Degeneration (nAMD)", "glycan_involvement": "VEGFA is a glycoprotein; glycosylation affects its secretion and receptor binding.", "mechanism": "VEGFA drives pathological angiogenesis in nAMD; suppression reduces neovascularization.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692710" }, { "confidence": "high", "disease": "Choroidal Neovascularization (CNV)", "glycan_involvement": "CD31 is heavily glycosylated; glycosylation modulates cell adhesion and angiogenesis.", "mechanism": "CD31 marks endothelial cells in neovascular lesions; reduction indicates suppressed CNV.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12692710" }, { "confidence": "high", "disease": "Subretinal fibrosis", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation influences ECM assembly and cell migration.", "mechanism": "Fibronectin upregulation marks fibrotic remodeling; RO-Exo suppresses fibronectin to reduce fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12692710" }, { "confidence": "medium", "disease": "Retinal Pigment Epithelium (RPE) degeneration", "glycan_involvement": "ZO-1 is glycosylated; glycosylation affects tight junction stability.", "mechanism": "ZO-1 marks RPE tight junctions; restoration by RO-Exo indicates improved RPE integrity.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12692710" }, { "confidence": "medium", "disease": "Neovascular Age-related Macular Degeneration (nAMD)", "glycan_involvement": "CD9 is glycosylated; glycosylation may affect exosome targeting.", "mechanism": "CD9 is an exosomal marker; presence in RO-Exo supports delivery to retinal cells.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692710" }, { "confidence": "medium", "disease": "Neovascular Age-related Macular Degeneration (nAMD)", "glycan_involvement": "CD63 is glycosylated; glycosylation may affect exosome targeting.", "mechanism": "CD63 is an exosomal marker; presence in RO-Exo supports delivery to retinal cells.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692710" }, { "confidence": "high", "disease": "Retinal Pigment Epithelium (RPE) degeneration", "glycan_involvement": "Fibronectin glycosylation modulates its role in EMT and cell adhesion.", "mechanism": "Fibronectin upregulation contributes to EMT and RPE dysfunction; RO-Exo suppresses fibronectin.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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reduction by RO-Exo signals therapeutic effect.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12692710" }, { "confidence": "medium", "disease": "Choroidal Neovascularization (CNV)", "glycan_involvement": "ZO-1 glycosylation stabilizes tight junctions.", "mechanism": "RO-Exo restores ZO-1-positive RPE monolayer, protecting against CNV-induced disruption.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12692710" }, { "confidence": "high", "disease": "Choroidal Neovascularization (CNV)", "glycan_involvement": "Fibronectin glycosylation affects ECM deposition in CNV.", "mechanism": "Fibronectin marks fibrotic changes in CNV lesions; suppression by RO-Exo reduces fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692710" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "LRP1 is a heavily N-glycosylated receptor; glycosylation is essential for its trafficking and ligand binding.", "mechanism": "Mediates amyloid-beta clearance across the blood-brain barrier; HAEE enhances LRP1-dependent A\u03b2 efflux, reducing amyloid burden.", "protein": "Low-Density Lipoprotein Receptor-Related Protein 1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692722" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Pgp is N-glycosylated; glycosylation affects its stability and localization at the BBB.", "mechanism": "Facilitates amyloid-beta transport across the BBB; HAEE increases Pgp-mediated A\u03b2 clearance, lowering brain amyloid levels.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692722" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation modulates its processing and A\u03b2 production.", "mechanism": "APP cleavage generates amyloid-beta, which aggregates and drives AD pathology.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12692722" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE is O-glycosylated; glycosylation influences receptor interactions and lipid binding.", "mechanism": "ApoE4 isoform impairs microglial A\u03b2 clearance and promotes neuroinflammation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "risk_factor", "source_pmcid": "PMC12692722" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation is required for surface expression and ligand binding.", "mechanism": "TREM2 supports microglial phagocytosis of A\u03b2; ApoE4 impairs TREM2 function, worsening AD.", "protein": "Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)", "relationship_type": "protective", "source_pmcid": "PMC12692722" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 is N-glycosylated; glycosylation is important for secretion and stability.", "mechanism": "Elevated IL-6 reflects microglial activation and neuroinflammation in AD; HAEE reduces IL-6, indicating anti-inflammatory effect.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692722" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "APP glycosylation affects A\u03b2 aggregation propensity.", "mechanism": "A\u03b2 aggregates from APP activate microglia, triggering chronic neuroinflammation.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12692722" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates Pgp function at the BBB.", "mechanism": "Reduced Pgp activity is associated with increased brain A\u03b2 and higher AD risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "risk_factor", "source_pmcid": "PMC12692722" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for LRP1 function.", "mechanism": "Enhanced LRP1-mediated A\u03b2 efflux reduces amyloid burden and improves cognition.", "protein": "Low-Density Lipoprotein Receptor-Related Protein 1", "relationship_type": "protective", "source_pmcid": "PMC12692722" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects IL-6 secretion.", "mechanism": "High IL-6 levels correlate with cognitive impairment and amyloid load in AD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692722" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "CFTR is glycosylated; glycosylation affects folding, trafficking, and function.", "mechanism": "Mutations in CFTR cause defective chloride/bicarbonate transport, leading to thick mucus and multisystem disease.", "protein": "CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)", "relationship_type": "causal", "source_pmcid": "PMC12692732" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "ADAM33 is a transmembrane glycoprotein; glycosylation may affect its proteolytic and adhesive functions.", "mechanism": "ADAM33 rs2280091 G allele is associated with improved peripheral airway function and bronchodilator response in CF.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/protective", "source_pmcid": "PMC12692732" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation may modulate ADAM33's activity in airway remodeling.", "mechanism": "ADAM33 variants (including rs2280091) are associated with increased airway inflammation, remodeling, and decline in lung function.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may influence ADAM33's role in skin cell interactions.", "mechanism": "ADAM33 polymorphisms are linked to early onset and progression via cell adhesion and epidermal remodeling.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation may affect ADAM33's function in skin.", "mechanism": "ADAM33 variants associated with cell adhesion and skin remodeling.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Nasal Polyposis", "glycan_involvement": "Glycosylation may regulate ADAM33's activity in nasal tissue.", "mechanism": "Upregulated ADAM33 expression in epithelial/mesenchymal cells contributes to airway remodeling.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may affect ADAM33's role in tumor cell migration.", "mechanism": "ADAM33 expression/methylation linked to tumor suppression or progression via cell migration.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/therapeutic target", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may modulate ADAM33's vascular functions.", "mechanism": "ADAM33 expression in vascular lesions inhibits smooth muscle cell migration, possibly protective.", "protein": "ADAM33 (A Disintegrin and Metalloproteinase Domain 33)", "protein_enriched": { "function": "", "gene_name": "ADAM33", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BZ11" }, "relationship_type": "modifier/protective", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Cystic Fibrosis", "glycan_involvement": "Extensive O-glycosylation critical for mucus properties.", "mechanism": "MUC4 contributes to mucus composition and epithelial protection; altered expression may affect CF severity.", "protein": "MUC4 (Mucin 4)", "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "medium", "disease": "Cystic Fibrosis", "glycan_involvement": "O-glycosylation essential for mucin function.", "mechanism": "MUC20 modulates mucus composition and epithelial defense in CF.", "protein": "MUC20 (Mucin 20)", "protein_enriched": { "function": "May play a role in the cell adhesion to the extracellular matrix", "gene_name": "MUC15", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q8N387" }, "relationship_type": "modifier/biomarker", "source_pmcid": "PMC12692732" }, { "confidence": "high", "disease": "Congenital Heart Disease (CHD)", "glycan_involvement": "HDL is a glycoprotein; glycosylation affects its structure and function.", "mechanism": "Low HDL is prevalent in CHD, especially in complex/cyanotic cases, reflecting altered lipid metabolism and endothelial dysfunction.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Arterial Thrombosis", "glycan_involvement": "Glycosylation modulates HDL's anti-inflammatory and anti-thrombotic functions.", "mechanism": "Low HDL is associated with increased arterial thrombosis risk in CHD, though not independently predictive after adjustment.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Eisenmenger Syndrome", "glycan_involvement": "Altered glycosylation may contribute to HDL dysfunction.", "mechanism": "Low HDL is more frequent in Eisenmenger syndrome, reflecting severe cardiometabolic dysregulation.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Ventricular Hypoplasia", "glycan_involvement": "Glycosylation status may affect HDL's vascular protective roles.", "mechanism": "Low HDL is more common in ventricular hypoplasia, indicating higher risk and disease complexity.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Arterial Thrombosis", "glycan_involvement": "LDL glycosylation influences atherogenicity.", "mechanism": "Mixed pattern of high LDL and low HDL is more frequent in CHD patients with thrombosis.", "protein": "Low-Density Lipoprotein (LDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "high", "disease": "Congenital Heart Disease (CHD)", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation affects its stability and clearance.", "mechanism": "NT-proBNP is elevated in complex CHD, reflecting cardiac dysfunction.", "protein": "N-terminal pro-B-type natriuretic peptide (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "CRP is elevated in CHD patients with low HDL, indicating inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "HDL glycosylation may affect its cardioprotective properties.", "mechanism": "Low HDL correlates with higher NT-proBNP, suggesting worse cardiac function.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12692766" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "Inflammation may alter HDL glycosylation, reducing function.", "mechanism": "Inflammation accelerates HDL catabolism and impairs biosynthesis.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "causal", "source_pmcid": "PMC12692766" }, { "confidence": "low", "disease": "Congenital Heart Disease (CHD)", "glycan_involvement": "Glycosylation status could influence therapeutic efficacy.", "mechanism": "HDL may serve as a target for risk stratification and intervention in CHD.", "protein": "High-Density Lipoprotein (HDL) cholesterol", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692766" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Glycosylation affects stability and clearance.", "mechanism": "Released from damaged cardiomyocytes; correlates with infarct size and LV dysfunction.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "high", "disease": "STEMI", "glycan_involvement": "Glycosylation modulates enzyme activity and serum half-life.", "mechanism": "Elevated in tissue injury; predicts infarct size and LV remodeling.", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Released in response to ventricular wall stress; predicts LV remodeling and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "high", "disease": "STEMI", "glycan_involvement": "Glycosylation influences isoenzyme separation and detection.", "mechanism": "Released from cardiac muscle during infarction; correlates with infarct size.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation affects serum stability.", "mechanism": "Elevated in myocardial and hepatic injury; part of multi-marker panel for LV remodeling.", "protein": "Aspartate Transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Elevated in tissue injury; included in prediction panels for LV remodeling.", "protein": "Alanine Transaminase (ALT)", "protein_enriched": { "function": "Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule", "gene_name": "rub", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24297" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "medium", "disease": "LV dysfunction", "glycan_involvement": "Glycosylation may affect immunoreactivity.", "mechanism": "Sensitive marker of myocardial injury; predicts LV function post-STEMI.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "low", "disease": "STEMI", "glycan_involvement": "Glycosylation essential for ligand binding and function.", "mechanism": "Acute-phase reactant; limited predictive value for LV function.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "low", "disease": "LV remodeling", "glycan_involvement": "Cell surface glycosylation modulates immune response.", "mechanism": "Leukocyte count included in predictive models for infarct size and remodeling.", "protein": "Leukocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "low", "disease": "STEMI", "glycan_involvement": "Glycosylation regulates platelet adhesion and aggregation.", "mechanism": "Platelet count used in ML models for infarct size prediction.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692794" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and receptor interaction.", "mechanism": "Impaired insulin sensitivity and secretion contribute to diabetes risk, especially under sleep deficiency.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "GLUT4 glycosylation is essential for proper trafficking and function.", "mechanism": "Physical activity increases GLUT4 translocation, improving glucose uptake and reducing diabetes risk.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "protective", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation affects secretion and receptor binding.", "mechanism": "Sleep deficiency alters leptin levels, promoting hyperphagia and obesity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Ghrelin glycosylation modulates stability and activity.", "mechanism": "Sleep deficiency increases ghrelin, stimulating appetite and weight gain.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "AMPK subunits are glycosylated, influencing activity and localization.", "mechanism": "Physical activity activates AMPK, improving metabolic health and reducing syndrome risk.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12692821" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic glycemic status; elevated in diabetes.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL-associated glycoproteins modulate lipid transport.", "mechanism": "Physical activity increases HDL, improving lipid profile.", "protein": "HDL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor interaction.", "mechanism": "Sleep deficiency and low physical activity increase TNF-\u03b1, promoting inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12692821" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "IL-6 glycosylation modulates stability and activity.", "mechanism": "Elevated IL-6 in sleep deficiency and low PA states drives systemic inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12692821" }, { "confidence": "low", "disease": "Depression", "glycan_involvement": "CBG glycosylation regulates cortisol binding and release.", "mechanism": "High physical activity and sleep deficiency may alter CBG, affecting cortisol bioavailability and mood.", "protein": "CBG", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12692821" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated serum AST reflects hepatocyte injury and correlates with fibrosis severity.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence secretion and activity.", "mechanism": "ALT elevation indicates hepatocellular damage, used in fibrosis indices.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function; altered glycosylation may affect count.", "mechanism": "Platelet count decreases with portal hypertension and fibrosis progression.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation may modulate AST half-life and detection.", "mechanism": "AST is included in FIB-4 and FIB-3 indices for non-invasive fibrosis assessment.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation may affect ALT stability and serum levels.", "mechanism": "ALT is a component of FIB-4 and FIB-3 indices for fibrosis screening.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation impacts platelet lifespan and immune clearance.", "mechanism": "Platelet count is reduced in chronic liver disease due to splenic sequestration and decreased thrombopoietin.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "medium", "disease": "Steatotic liver disease (SLD)", "glycan_involvement": "Glycosylation may influence AST release and detection.", "mechanism": "AST is elevated in SLD and used in fibrosis indices.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "medium", "disease": "Steatotic liver disease (SLD)", "glycan_involvement": "Glycosylation may affect ALT activity and serum stability.", "mechanism": "ALT is elevated in SLD and included in fibrosis indices.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "Altered glycosylation may affect platelet clearance in liver disease.", "mechanism": "Platelet count is a marker of advanced fibrosis in MASH.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "medium", "disease": "Alcohol-related liver disease", "glycan_involvement": "Glycosylation changes may contribute to altered platelet function.", "mechanism": "Platelet count is reduced in alcohol-related liver disease, reflecting fibrosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12692902" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "HIF-1\u03b1 is glycosylated, which may affect stability and activity.", "mechanism": "Promotes M1 macrophage polarization and glycolysis, driving fibrosis; inhibition by ACBA alleviates fibrosis.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "PFKFB3 is glycosylated, influencing enzyme activity.", "mechanism": "Upregulated by HIF-1\u03b1, enhances glycolysis in macrophages, promoting pro-inflammatory phenotype and fibrosis.", "protein": "PFKFB3", "protein_enriched": { "function": "Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate", "gene_name": "PFKFB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16875" }, "relationship_type": "causal", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "CD86 is heavily glycosylated, affecting cell-cell interactions.", "mechanism": "Marker of M1 macrophages; increased expression correlates with inflammation and fibrosis progression.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "CD163 glycosylation modulates receptor function and anti-inflammatory signaling.", "mechanism": "Marker of M2 macrophages; increased expression associated with anti-inflammatory response and tissue repair.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "protective", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Collagen I is glycosylated, affecting fibril formation and stability.", "mechanism": "Major ECM component; excessive deposition leads to fibrotic scarring.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12692955" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation may regulate HIF-1\u03b1 stability in hypoxic conditions.", "mechanism": "Promotes myeloid macrophage polarization via PFKFB3, driving renal fibrosis.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12692955" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect HIF-1\u03b1 transcriptional activity in tumor microenvironment.", "mechanism": "Chronic activation in fibrosis can progress to cancer.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation modulates enzyme activity and stability.", "mechanism": "Enhances glycolytic flux in macrophages, promoting inflammatory cytokine production.", "protein": "PFKFB3", "protein_enriched": { "function": "Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate", "gene_name": "PFKFB3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16875" }, "relationship_type": "causal", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation affects ligand binding and immune activation.", "mechanism": "Elevated in pro-inflammatory macrophages during liver injury.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation regulates anti-inflammatory signaling.", "mechanism": "Associated with resolution of inflammation and tissue repair.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "protective", "source_pmcid": "PMC12692955" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Altered glycosylation may affect albumin stability and clearance.", "mechanism": "Hypoalbuminemia indicates impaired liver synthetic function in DILI.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects ALP activity and membrane localization.", "mechanism": "Elevated ALP reflects cholestatic or mixed liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation required for GGT function and stability.", "mechanism": "Elevated GGT is a marker of cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "Elevated IgG levels are characteristic of AIH.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ANA are glycoproteins; glycosylation affects antigenicity.", "mechanism": "Positive ANA supports diagnosis of AIH.", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ASMA glycosylation may affect immune recognition.", "mechanism": "ASMA positivity is diagnostic for AIH.", "protein": "Anti-smooth muscle antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation regulates sFlt-1 secretion and activity.", "mechanism": "Elevated sFlt-1/PlGF ratio is diagnostic for preeclampsia.", "protein": "Soluble fms-like tyrosine kinase-1 (sFlt-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects PlGF stability and receptor binding.", "mechanism": "Low PlGF levels contribute to preeclampsia pathogenesis.", "protein": "Placental growth factor (PlGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12692966" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation influences CYP folding and localization.", "mechanism": "CYP-mediated metabolism of drugs generates reactive metabolites causing DILI.", "protein": "Cytochrome P450 enzymes", "relationship_type": "causal", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Glycosylation required for transporter trafficking and function.", "mechanism": "Reduced transporter expression/function leads to bile acid accumulation in ICP.", "protein": "Bile acid transporters (BSEP/ABCB11)", "relationship_type": "causal", "source_pmcid": "PMC12692966" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 on host cells.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which affects spike binding affinity.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2 spike protein, enabling viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates immune evasion and receptor interaction.", "mechanism": "Spike glycoprotein mediates SARS-CoV entry via ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC12692970" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation shields spike protein from immune recognition.", "mechanism": "MERS-CoV spike glycoprotein mediates viral entry (via DPP4, not ACE2).", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences RBD conformation and accessibility to inhibitors.", "mechanism": "Spike RBD is targeted by antiviral compounds (e.g., garlic-derived phytochemicals) to block ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans can mask antibody epitopes, affecting neutralization.", "mechanism": "Monoclonal antibodies target spike glycoprotein to neutralize virus.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation state affects ACE2's decoy efficacy.", "mechanism": "Soluble ACE2 can act as a decoy receptor, reducing viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "protective", "source_pmcid": "PMC12692970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate compound access to RBD interface.", "mechanism": "Garlic-derived organosulfur compounds predicted to bind RBD, inhibiting spike\u2013ACE2 interaction.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect inhibitor binding.", "mechanism": "Methylene blue inhibits spike\u2013ACE2 interaction in vitro.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity.", "mechanism": "Spike protein presence is used for COVID-19 diagnosis.", "protein": "SARS-CoV-2 Spike glycoprotein (S protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12692970" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT reflects hepatocellular injury and oxidative stress in MASLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated, which influences its serum levels.", "mechanism": "Elevated AST indicates liver cell damage in MASLD and MASH.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT glycosylation modulates its activity and release.", "mechanism": "ALT elevation is a marker of hepatocellular injury in MASLD/MASH.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Apolipoproteins in VLDL are glycosylated, affecting lipid transport.", "mechanism": "Elevated VLDL reflects hepatic lipid export dysfunction in MASLD.", "protein": "Triglyceride-rich lipoproteins (VLDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Keratin glycosylation influences aggregate formation.", "mechanism": "Presence of Mallory\u2013Denk bodies indicates cytoskeletal disruption in MASH.", "protein": "Mallory\u2013Denk bodies (keratin glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Collagen glycosylation affects fibril formation and tissue remodeling.", "mechanism": "Collagen deposition marks progression to fibrosis in MASLD/MASH.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation of insulin receptor modulates its function.", "mechanism": "Defective insulin signaling promotes MASLD progression.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation regulates NF-\u03baB nuclear translocation and activity.", "mechanism": "NF-\u03baB activation drives hepatic inflammation in MASH.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL apolipoproteins are glycosylated, influencing cholesterol transport.", "mechanism": "Low HDL is a risk factor for MASLD and metabolic syndrome.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL glycosylation affects receptor binding and clearance.", "mechanism": "Elevated LDL is associated with metabolic syndrome and MASLD risk.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693011" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "NT-proBNP is glycosylated, affecting its stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac dysfunction and ventricular stress.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "high", "disease": "Cardiac sarcoidosis", "glycan_involvement": "Glycosylation modulates NT-proBNP plasma levels.", "mechanism": "NT-proBNP increases with sarcoid-related myocardial injury and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "medium", "disease": "Cardiac sarcoidosis", "glycan_involvement": "ACE is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "ACE is elevated in systemic sarcoidosis due to granuloma formation.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "medium", "disease": "Cardiac sarcoidosis", "glycan_involvement": "sIL-2R glycosylation influences its serum detection.", "mechanism": "sIL-2R reflects T-cell activation in granulomatous inflammation.", "protein": "Soluble interleukin-2 receptor (sIL-2R)", "protein_enriched": { "function": "Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation", "gene_name": "IL2RB", "glycan_count": 5, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49955PK", "G57317CE", "G61256FT", "G74381CZ", "G92050GC" ], "uniprot_id": "P14784" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "high", "disease": "Staphylococcus aureus bacteremia", "glycan_involvement": "CRP glycosylation affects its immunological function.", "mechanism": "CRP rises in response to infection and systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "medium", "disease": "Cardiac sarcoidosis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP may be elevated in active sarcoid inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "high", "disease": "Staphylococcus aureus bacteremia", "glycan_involvement": "Glycosylation affects procalcitonin's stability and detection.", "mechanism": "Procalcitonin increases in bacterial infection and sepsis.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "medium", "disease": "Complete heart block", "glycan_involvement": "Glycosylation impacts NT-proBNP's half-life.", "mechanism": "NT-proBNP may be mildly elevated in conduction disorders with ventricular dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "ACE glycosylation affects its plasma activity.", "mechanism": "ACE levels may be altered in heart failure due to neurohormonal activation.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "Glycosylation influences sIL-2R's immunological role.", "mechanism": "sIL-2R may reflect immune activation in heart failure.", "protein": "Soluble interleukin-2 receptor (sIL-2R)", "protein_enriched": { "function": "Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation", "gene_name": "IL2RB", "glycan_count": 5, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49955PK", "G57317CE", "G61256FT", "G74381CZ", "G92050GC" ], "uniprot_id": "P14784" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693021" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "HER2 is a heavily N-glycosylated receptor; glycosylation affects receptor stability and antibody binding.", "mechanism": "HER2 overexpression drives cell proliferation, survival, and poor prognosis; targeted by T-DXd ADC for cytotoxic delivery.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693061" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation modulates HER2 function and antibody recognition.", "mechanism": "HER2 overexpression is a key driver in breast cancer; targeted by trastuzumab and T-DXd.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693061" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "N-glycosylation influences HER2 stability and immune recognition.", "mechanism": "HER2 overexpression is associated with aggressive gastric cancer; targeted by T-DXd.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693061" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "N-glycosylation affects HER2 receptor conformation and antibody binding.", "mechanism": "HER2 mutation/overexpression in NSCLC enables T-DXd targeting.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693061" }, { "confidence": "high", "disease": "Platinum-resistant Ovarian Cancer", "glycan_involvement": "FR\u03b1 is N-glycosylated, which affects cell surface localization and antibody accessibility.", "mechanism": "FR\u03b1 is highly expressed in platinum-resistant OC; targeted by MIRV ADC for cytotoxic delivery.", "protein": "Folate Receptor Alpha (FR\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693061" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Fc glycosylation modulates antibody effector function and pharmacokinetics.", "mechanism": "Trastuzumab component of T-DXd binds HER2 on OC cells, enabling targeted cytotoxicity.", "protein": "IgG1 (Trastuzumab antibody)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12693061" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation status may influence HER2 detection and antibody binding.", "mechanism": "HER2 expression level predicts response to T-DXd therapy in OC.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "biomarker", "source_pmcid": "PMC12693061" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation affects FR\u03b1 stability and antibody recognition.", "mechanism": "FR\u03b1 expression level predicts response to MIRV therapy in OC.", "protein": "Folate Receptor Alpha (FR\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12693061" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "N-glycosylation modulates HER2 signaling and cell surface expression.", "mechanism": "HER2 overexpression contributes to OC aggressiveness, recurrence, and chemoresistance.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "causal", "source_pmcid": "PMC12693061" }, { "confidence": "medium", "disease": "Cardiac Dysfunction (secondary to therapy)", "glycan_involvement": "Fc glycosylation may influence immune-mediated cardiac toxicity.", "mechanism": "HER2 blockade by trastuzumab can disrupt cardiac signaling, leading to heart failure.", "protein": "IgG1 (Trastuzumab antibody)", "relationship_type": "causal (adverse effect)", "source_pmcid": "PMC12693061" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "gp210 is a nuclear envelope glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-gp210 antibodies are highly specific for PBC and predict poor prognosis (cirrhosis, hepatic failure, mortality).", "protein": "gp210", "protein_enriched": { "function": "Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and t", "gene_name": "JUP", "glycan_count": 12, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G43089EG", "G52527GH", "G75983OB", "G13694XX", "G22310AV", "G56784JY", "G57888GL", "G06356OH", "G11629QQ", "G84452RH" ], "uniprot_id": "P14923" }, "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC12693065" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "sp100 is a nuclear body glycoprotein; glycosylation may influence immune recognition.", "mechanism": "Anti-sp100 antibodies are highly specific for PBC and aid diagnosis, especially in AMA-negative cases.", "protein": "sp100", "protein_enriched": { "function": "Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation a", "gene_name": "SP100", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P23497" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Lipoic acid moiety (not a glycan) is modified; glycosylation not directly implicated but mitochondrial protein context relevant.", "mechanism": "AMAs target PDC-E2 neoantigen formed by bile acid-induced modification, central to PBC pathogenesis.", "protein": "PDC-E2 (Pyruvate Dehydrogenase Complex E2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "KLHL12 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-KLHL12 antibodies are present in ~40% of PBC, including marker-negative cases; associated with fibrosis and poor outcomes.", "protein": "KLHL12", "protein_enriched": { "function": "Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). Th", "gene_name": "KLHL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q53G59" }, "relationship_type": "biomarker/risk factor", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Potential glycoprotein; glycosylation status not specified.", "mechanism": "Anti-RPL30 antibodies are highly specific for PBC, especially in seronegative cases; correlate with disease severity.", "protein": "RPL30", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, P", "gene_name": "RPL30", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62888" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "LBR is a glycoprotein; glycosylation may influence immune recognition.", "mechanism": "Anti-LBR antibodies are highly specific for PBC, including AMA-negative cases; associated with hepatic fibrosis.", "protein": "Lamin B Receptor (LBR)", "protein_enriched": { "function": "Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis (PubMed:12618959, PubMed:16784888, PubMed:21327084, PubMed:27336", "gene_name": "LBR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14739" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "p62 is a glycoprotein component of the nuclear pore complex.", "mechanism": "Anti-p62 antibodies are highly specific for PBC and serve as supplementary markers in seronegative patients.", "protein": "Nucleoporin p62", "protein_enriched": { "function": "Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein int", "gene_name": "NUP62", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P37198" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "low", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Anti-HK1 antibodies are more frequent in PBC than controls; specificity 96.9%.", "protein": "Hexokinase-1 (HK1)", "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "gp210 glycosylation may affect immune recognition.", "mechanism": "Anti-gp210 positivity predicts progression to cirrhosis and end-stage liver failure in PBC.", "protein": "gp210", "protein_enriched": { "function": "Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and t", "gene_name": "JUP", "glycan_count": 12, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G43089EG", "G52527GH", "G75983OB", "G13694XX", "G22310AV", "G56784JY", "G57888GL", "G06356OH", "G11629QQ", "G84452RH" ], "uniprot_id": "P14923" }, "relationship_type": "prognostic", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "AIH\u2013PBC Overlap Syndrome", "glycan_involvement": "sp100 glycosylation may influence antigenicity.", "mechanism": "Anti-sp100 antibodies are more frequent in overlap syndrome than in pure PBC.", "protein": "sp100", "protein_enriched": { "function": "Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation a", "gene_name": "SP100", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P23497" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693065" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects P-glycoprotein trafficking and function at the BBB.", "mechanism": "Reduced P-glycoprotein-mediated efflux at the blood-brain barrier increases CNS exposure to \u03b1-blockers, potentially exacerbating cognitive decline.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates receptor localization and signaling.", "mechanism": "Reduced \u03b11A-adrenoceptor expression in the brain is associated with dementia; antagonism may blunt cognitive processes.", "protein": "\u03b11A-adrenoceptor", "protein_enriched": { "function": "This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) protein", "gene_name": "ADRA1A", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35348" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation influences receptor stability and CNS function.", "mechanism": "Central \u03b11A-adrenoceptor antagonism may reduce noradrenergic tone, contributing to depressive symptoms.", "protein": "\u03b11A-adrenoceptor", "protein_enriched": { "function": "This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) protein", "gene_name": "ADRA1A", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35348" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation regulates PGK1 activity and cellular localization.", "mechanism": "Quinazoline \u03b1-blockers (e.g., terazosin) activate PGK1, increasing ATP and showing neuroprotective effects.", "protein": "Phosphoglycerate kinase-1", "protein_enriched": { "function": "Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and ", "gene_name": "PGK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00558" }, "relationship_type": "protective", "source_pmcid": "PMC12693173" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects receptor function in astrocytes.", "mechanism": "Antagonism impairs Ca2+-dependent gliotransmission, affecting memory consolidation.", "protein": "Astrocytic \u03b11A-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "low", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates microglial receptor activity.", "mechanism": "\u03b11A antagonism may alter microglial reactivity, influencing neuroinflammation and dementia risk.", "protein": "Microglial \u03b11A-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation is essential for P-glycoprotein function at the BBB.", "mechanism": "Age-related decline in P-glycoprotein function increases CNS drug exposure, raising cognitive risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "low", "disease": "Unintentional injury", "glycan_involvement": "Glycosylation affects receptor signaling in CNS circuits.", "mechanism": "Central antagonism may impair arousal and attention, increasing injury risk.", "protein": "\u03b11A-adrenoceptor", "protein_enriched": { "function": "This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) protein", "gene_name": "ADRA1A", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35348" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation regulates PGK1 enzymatic activity.", "mechanism": "PGK1 activation by terazosin increases ATP, potentially counteracting neurodegeneration.", "protein": "Phosphoglycerate kinase-1", "protein_enriched": { "function": "Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and ", "gene_name": "PGK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00558" }, "relationship_type": "protective", "source_pmcid": "PMC12693173" }, { "confidence": "low", "disease": "Depression", "glycan_involvement": "Glycosylation is critical for transporter function.", "mechanism": "Impaired P-glycoprotein function may increase CNS drug levels, affecting mood regulation.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12693173" }, { "confidence": "high", "disease": "Intestinal permeability/gut barrier dysfunction", "glycan_involvement": "Zonulin is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "Zonulin regulates tight junctions, increased levels indicate higher intestinal permeability.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation may modulate zonulin's activity in barrier regulation.", "mechanism": "Elevated zonulin was hypothesized to link gut permeability to ASCVD risk, but no independent association found.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation critical for stability and function.", "mechanism": "Part of FibroTest panel; increased levels reflect hepatic fibrosis.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences lipid binding and anti-inflammatory properties.", "mechanism": "Component of FibroTest; decreased levels associated with fibrosis.", "protein": "Apolipoprotein A1", "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates immune function and clearance.", "mechanism": "FibroTest component; altered levels indicate hepatic inflammation/fibrosis.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects enzyme activity and stability.", "mechanism": "Included in FibroTest; elevated GGT reflects liver injury/fibrosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Panel relies on glycoprotein markers whose glycosylation status affects diagnostic accuracy.", "mechanism": "FibroTest (glycoprotein panel) used to assess liver fibrosis; no independent association with ASCVD risk found.", "protein": "FibroTest panel", "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "Glycosylation impacts zonulin's regulatory role in MASLD.", "mechanism": "Elevated zonulin may reflect gut\u2013liver axis dysfunction in MASLD.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation modulates anti-atherogenic functions.", "mechanism": "Higher ApoA1 levels are generally protective against ASCVD; included in risk scoring.", "protein": "Apolipoprotein A1", "relationship_type": "protective", "source_pmcid": "PMC12693247" }, { "confidence": "low", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation pattern changes in inflammation and may influence ASCVD risk.", "mechanism": "Altered haptoglobin glycoforms may be linked to vascular inflammation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693247" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Aberrant glycosylation of MUC1 in cancer enhances diagnostic specificity.", "mechanism": "Tumor-selective MUC1 promoter drives reporter gene expression for cancer detection.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "CD44 glycosylation modulates cell adhesion and tumor progression.", "mechanism": "Cancer-targeted nanoassembly responsive to CD44 releases detectable reporter in blood.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Liver metastasis", "glycan_involvement": "\u03b2-galactosidase cleaves glycosidic bonds in glycoproteins/glycans for signal generation.", "mechanism": "Engineered E. coli expressing \u03b2-galactosidase colonizes tumors, enabling urine-based detection.", "protein": "\u03b2-galactosidase", "protein_enriched": { "function": "", "gene_name": "lacZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00722" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "APN is a glycoprotein; glycosylation affects substrate specificity and tumor invasion.", "mechanism": "APN-cleavable synthetic probe releases fluorescent reporter for cancer detection.", "protein": "Aminopeptidase N (APN)", "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Thrombin glycosylation influences activity and stability.", "mechanism": "Thrombin-activated nanosensors release reporters for noninvasive thrombosis diagnosis.", "protein": "Thrombin", "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "GzmB glycosylation modulates secretion and activity.", "mechanism": "GzmB-cleavable nanosensors detect early immune-mediated organ rejection.", "protein": "Granzyme B (GzmB)", "protein_enriched": { "function": "Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubM", "gene_name": "GZMB", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P10144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "medium", "disease": "Organ transplant rejection", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects enzymatic activity.", "mechanism": "GGT-activated probes enable early detection of renal allograft rejection.", "protein": "\u03b3-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "medium", "disease": "Metastatic melanoma", "glycan_involvement": "SEAP glycosylation influences secretion and stability.", "mechanism": "Tumor-activatable minicircle expresses SEAP for blood-based cancer detection.", "protein": "Secreted embryonic alkaline phosphatase (SEAP)", "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "GFAP is glycosylated; glycan status may affect biomarker performance.", "mechanism": "GFAP compared to synthetic calpain-activated probes for TBI diagnosis.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Calpain is glycosylated; glycosylation may regulate protease activity.", "mechanism": "Calpain-activated nanosensors release fluorescent reporters for early TBI detection.", "protein": "Calpain", "protein_enriched": { "function": "Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:19617626, PubMed:21531719, PubMed:2", "gene_name": "CAPN1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "P07384" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693320" }, { "confidence": "high", "disease": "Liver transplant rejection", "glycan_involvement": "CRP is a heavily glycosylated protein; glycosylation affects its stability and immune recognition.", "mechanism": "CRP levels rise in response to inflammation and correlate with cfDNA during rejection episodes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "high", "disease": "Primary graft dysfunction", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells.", "mechanism": "Elevated CRP reflects acute phase response to graft injury.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Ischemia\u2013reperfusion injury", "glycan_involvement": "Histones and nucleosome-associated proteins may be glycosylated, influencing immune activation.", "mechanism": "cfDNA and nucleosomes act as DAMPs, triggering inflammation after IRI.", "protein": "cfDNA-associated nucleosomes (histone-bound DNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects CRP's clearance and function.", "mechanism": "CRP is elevated in systemic inflammation and sepsis post-transplant.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Gamma-GT is glycosylated; glycan changes may affect enzyme activity.", "mechanism": "Gamma-GT levels inversely correlate with cfDNA during acute liver injury.", "protein": "Gamma-glutamyltransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "ALT is glycosylated; glycosylation may affect stability.", "mechanism": "ALT levels rise with hepatocyte injury and correlate with cfDNA.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "AST is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "AST levels rise with liver injury and correlate with cfDNA.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Chronic liver dysfunction", "glycan_involvement": "Altered glycosylation may affect CRP's role in chronic inflammation.", "mechanism": "Persistent elevation of CRP indicates ongoing inflammation and chronic dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Liver transplant rejection", "glycan_involvement": "Glycosylation of nucleosome proteins may modulate immune response.", "mechanism": "Elevated cfDNA reflects cell death during rejection.", "protein": "cfDNA-associated nucleosomes (histone-bound DNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "medium", "disease": "Ischemia\u2013reperfusion injury", "glycan_involvement": "Glycosylation influences CRP's inflammatory signaling.", "mechanism": "CRP peaks after cfDNA, indicating inflammatory response to IRI.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693361" }, { "confidence": "high", "disease": "Allograft dysfunction", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects stability and serum half-life.", "mechanism": "Elevated GGT indicates biliary/graft dysfunction post-transplant.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Allograft dysfunction", "glycan_involvement": "AP is N-glycosylated; glycosylation modulates secretion and activity.", "mechanism": "Elevated AP is a marker of cholestasis and biliary complications.", "protein": "Alkaline phosphatase (AP)", "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Allograft dysfunction", "glycan_involvement": "ALT is glycosylated; glycosylation may affect serum detection.", "mechanism": "ALT elevation signals hepatocellular injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Allograft dysfunction", "glycan_involvement": "AST is glycosylated; glycosylation impacts stability.", "mechanism": "AST elevation reflects liver cell injury.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Liver transplant rejection", "glycan_involvement": "FKBP12 is not glycosylated, but tacrolimus acts via glycoprotein complexes.", "mechanism": "FKBP12 binds tacrolimus, inhibiting calcineurin and T-cell activation.", "protein": "Tacrolimus-binding protein FKBP12", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693376" }, { "confidence": "medium", "disease": "Tacrolimus toxicity/renal insufficiency", "glycan_involvement": "CYP3A4 is glycosylated; glycosylation affects enzyme stability.", "mechanism": "CYP3A4 metabolizes tacrolimus; polymorphisms affect drug levels and toxicity.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12693376" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "LDL receptor N-glycosylation is critical for function.", "mechanism": "Immunosuppression can alter LDL receptor function, raising cholesterol.", "protein": "Cholesterol transporter (LDL receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "medium", "disease": "Post-liver transplantation diabetes mellitus (PLTDM)", "glycan_involvement": "GLUT1 N-glycosylation is essential for trafficking and function.", "mechanism": "Immunosuppressants may impair GLUT1, affecting glucose homeostasis.", "protein": "Glucose transporter (GLUT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Renal insufficiency/failure", "glycan_involvement": "Tacrolimus interacts with glycoprotein targets in kidney cells.", "mechanism": "High tacrolimus levels cause nephrotoxicity.", "protein": "Tacrolimus (FK506)", "relationship_type": "causal", "source_pmcid": "PMC12693376" }, { "confidence": "medium", "disease": "Allograft dysfunction", "glycan_involvement": "Albumin glycosylation affects bilirubin binding and clearance.", "mechanism": "Elevated bilirubin reflects impaired liver function.", "protein": "Total bilirubin (albumin-bound)", "relationship_type": "biomarker", "source_pmcid": "PMC12693376" }, { "confidence": "high", "disease": "Subconjunctival fibrosis", "glycan_involvement": "SPARC is a glycoprotein; glycosylation may affect secretion and ECM interactions.", "mechanism": "SPARC activates fibroblasts, increasing ECM production and collagen deposition at wound sites.", "protein": "SPARC", "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "high", "disease": "Bleb scarring", "glycan_involvement": "TGF\u03b22 is glycosylated; glycosylation modulates receptor binding and stability.", "mechanism": "TGF\u03b22 drives fibroblast activation and ECM deposition, leading to scarring after glaucoma surgery.", "protein": "TGF\u03b22", "protein_enriched": { "function": "Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively", "gene_name": "TGFB2", "glycan_count": 7, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G06110VR", "G41247ZX", "G62765YT", "G80920RR", "G49108TO", "G83460ZZ" ], "uniprot_id": "P61812" }, "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "high", "disease": "Bleb scarring", "glycan_involvement": "VEGF-A glycosylation affects receptor interaction and angiogenic activity.", "mechanism": "VEGF-A promotes angiogenesis and fibroblast proliferation, increasing risk of scar formation.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "high", "disease": "Trabeculectomy failure", "glycan_involvement": "MCP-1 is glycosylated; glycosylation influences chemokine activity and stability.", "mechanism": "High MCP-1 levels in tears/aqueous humour predict increased risk of surgical failure.", "protein": "MCP-1/CCL2", "relationship_type": "biomarker", "source_pmcid": "PMC12693394" }, { "confidence": "medium", "disease": "Wound healing disorder", "glycan_involvement": "MMPs are glycoproteins; glycosylation affects secretion and substrate specificity.", "mechanism": "MMPs remodel ECM; inhibition prolongs bleb survival and reduces excessive scarring.", "protein": "MMPs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693394" }, { "confidence": "medium", "disease": "Subconjunctival fibrosis", "glycan_involvement": "PDGF glycosylation modulates receptor binding and mitogenic activity.", "mechanism": "PDGF released during haemostasis and proliferation recruits fibroblasts and promotes ECM synthesis.", "protein": "PDGF", "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "medium", "disease": "Subconjunctival fibrosis", "glycan_involvement": "CTGF is glycosylated; glycosylation affects ECM binding and cell signaling.", "mechanism": "CTGF amplifies TGF\u03b2-induced fibroblast activation and ECM production.", "protein": "CTGF", "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "medium", "disease": "Bleb scarring", "glycan_involvement": "FGF-2 glycosylation influences receptor interaction and stability.", "mechanism": "FGF-2 stimulates fibroblast proliferation and angiogenesis, contributing to scar formation.", "protein": "FGF-2", "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Receptor glycosylation modulates ligand binding and cell signaling.", "mechanism": "Promotes vasoconstriction and platelet activation, initiating inflammatory response post-surgery.", "protein": "Thromboxane A2 receptor", "protein_enriched": { "function": "Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger", "gene_name": "TBXA2R", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P21731" }, "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "low", "disease": "Wound healing disorder", "glycan_involvement": "PF4 glycosylation affects chemokine activity and immune cell recruitment.", "mechanism": "PF4 released by platelets recruits inflammatory cells and modulates fibroblast activity.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC12693394" }, { "confidence": "high", "disease": "Infant health disorders", "glycan_involvement": "Glycosylation modulates OPN's bioactivity and stability in milk.", "mechanism": "Milk-derived OPN supports immune function and development in infants.", "protein": "Osteopontin (OPN)", "relationship_type": "protective", "source_pmcid": "PMC12693450" }, { "confidence": "medium", "disease": "Human health disorders", "glycan_involvement": "Phosphorylation and glycosylation affect OPN's signaling and interactions.", "mechanism": "OPN levels and glycosylation patterns are associated with various health conditions.", "protein": "Osteopontin (OPN)", "relationship_type": "biomarker", "source_pmcid": "PMC12693450" }, { "confidence": "high", "disease": "Infectious diseases", "glycan_involvement": "Glycosylation is essential for LPO's stability and enzymatic activity.", "mechanism": "LPO catalyzes antimicrobial reactions in milk, protecting against pathogens.", "protein": "Lactoperoxidase (LPO)", "protein_enriched": { "function": "Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2) (Probable) (Pu", "gene_name": "LPO", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P80025" }, "relationship_type": "protective", "source_pmcid": "PMC12693450" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Plin2 is a glycoprotein; glycosylation may affect stability and LD association.", "mechanism": "Overexpression inhibits LD lipolysis, promoting lipid accumulation in hepatocytes.", "protein": "Plin2 (Perilipin 2)", "protein_enriched": { "function": "Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets", "gene_name": "PLIN2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99541" }, "relationship_type": "causal", "source_pmcid": "PMC12693466" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Plin5 is a glycoprotein; glycosylation may modulate LD-mitochondria interactions.", "mechanism": "Overexpression inhibits ATGL/CGI-58-mediated LD lipolysis, increasing lipid storage.", "protein": "Plin5 (Perilipin 5)", "protein_enriched": { "function": "", "gene_name": "GYPA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WTS2" }, "relationship_type": "causal", "source_pmcid": "PMC12693466" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation critical for chaperone function.", "mechanism": "Upregulated during ER stress, indicating hepatocyte stress in steatosis.", "protein": "GRP78 (BiP/HSPA5)", "relationship_type": "biomarker", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation required for ER localization and function.", "mechanism": "Activation triggers UPR, leading to downstream effects on lipid metabolism.", "protein": "PERK (EIF2AK3)", "relationship_type": "causal", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "Induced by ER stress, upregulates PPAR\u03b3, increasing Plin2/Plin5 and lipid accumulation.", "protein": "CHOP (DDIT3)", "relationship_type": "causal", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulates Plin2/Plin5, promoting LD accumulation.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect detection as biomarker.", "mechanism": "Elevated in MASLD; marker of LD accumulation.", "protein": "Plin2 (Perilipin 2)", "protein_enriched": { "function": "Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets", "gene_name": "PLIN2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99541" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect detection as biomarker.", "mechanism": "Elevated in MASLD; marker of LD accumulation.", "protein": "Plin5 (Perilipin 5)", "protein_enriched": { "function": "", "gene_name": "GYPA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WTS2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Indicates ER stress in MASLD progression.", "protein": "GRP78 (BiP/HSPA5)", "relationship_type": "biomarker", "source_pmcid": "PMC12693466" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect stability and detection.", "mechanism": "Upregulated in NAFLD, correlates with disease severity.", "protein": "Plin2 (Perilipin 2)", "protein_enriched": { "function": "Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets", "gene_name": "PLIN2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99541" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693466" }, { "confidence": "high", "disease": "Hypoplastic Left Heart Syndrome (HLHS)", "glycan_involvement": "NT-proBNP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated NT-proBNP reflects reduced ventricular function and cardiac stress in HLHS patients post-Fontan.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "high", "disease": "Failing Fontan circulation", "glycan_involvement": "Glycosylation modulates NT-proBNP half-life and detection.", "mechanism": "High NT-proBNP levels indicate cardiac failure and adverse outcomes in failing Fontan.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Protein-losing enteropathy (PLE)", "glycan_involvement": "Albumin glycosylation influences its stability and loss in PLE.", "mechanism": "Low serum albumin is a marker of PLE, a complication of Fontan physiology.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "GGT is glycosylated; glycan changes may reflect liver pathology.", "mechanism": "Elevated GGT is indicative of liver dysfunction in FALD after Fontan.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "AST glycosylation may affect enzyme activity and release.", "mechanism": "Elevated AST signals hepatic injury in FALD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "ALT glycosylation may influence its serum levels.", "mechanism": "ALT elevation is a marker of liver cell injury in FALD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "high", "disease": "Cardiac decompensation", "glycan_involvement": "Glycosylation affects NT-proBNP clearance and measurement.", "mechanism": "NT-proBNP rises during cardiac decompensation events in Fontan patients.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Failing Fontan circulation", "glycan_involvement": "Loss of glycosylated albumin may reflect enteropathy.", "mechanism": "Hypoalbuminemia is associated with failing Fontan and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "medium", "disease": "Fontan-associated liver disease (FALD)", "glycan_involvement": "Glycosylation impacts NT-proBNP stability in circulation.", "mechanism": "Elevated NT-proBNP may correlate with hepatic congestion and FALD.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "low", "disease": "Failing Fontan circulation", "glycan_involvement": "Glycosylation status may change with liver dysfunction.", "mechanism": "GGT elevation may signal hepatic congestion in failing Fontan.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693486" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation required for proper folding, trafficking, and surface expression.", "mechanism": "Overexpressed in tumors, mediates iron uptake, supports proliferation, survival, metastasis, and therapy resistance.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693568" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation status may affect receptor stability and detection.", "mechanism": "High CD71 expression correlates with aggressive phenotype, poor prognosis, and reduced survival.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation required for receptor function in cardiomyocytes.", "mechanism": "Reduced CD71 expression in failing myocardium impairs iron uptake, contributing to cardiac dysfunction.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation necessary for receptor-mediated iron uptake.", "mechanism": "Knockdown of CD71 reduces atrial fibrillation by limiting ferroptosis and fibrosis.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects BBB transport and receptor function.", "mechanism": "CD71 dysregulation increases brain iron influx, ROS, and neurodegeneration.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation impacts receptor stability and iron transport.", "mechanism": "Altered CD71 expression contributes to iron accumulation and redox imbalance in PD brains.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation required for apical/basolateral membrane localization.", "mechanism": "Inflammation-driven HIF-1\u03b1 signaling upregulates CD71, increasing epithelial iron uptake and ROS.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "medium", "disease": "Anemia of Chronic Disease", "glycan_involvement": "Glycosylation affects receptor function in erythroid precursors.", "mechanism": "Inflammation elevates hepcidin, restricts iron, and alters CD71-mediated uptake, worsening anemia.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "causal", "source_pmcid": "PMC12693568" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation required for transferrin binding to CD71.", "mechanism": "Transferrin-drug conjugates exploit CD71-mediated uptake for targeted cytotoxicity.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693568" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation influences receptor expression on immune cells.", "mechanism": "CD71-mediated iron uptake in TME supports immunosuppressive macrophage polarization and Treg expansion.", "protein": "CD71 (Transferrin Receptor 1, TfR1)", "relationship_type": "immune evasion", "source_pmcid": "PMC12693568" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Cell surface glycosylation mediates immune cell trafficking.", "mechanism": "CD11b marks neutrophil infiltration, increased in alcohol/HFD-induced liver inflammation.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation regulates macrophage function and migration.", "mechanism": "F4/80 marks macrophage infiltration, upregulated in inflamed liver after alcohol/HFD.", "protein": "F4/80 (EMR1)", "protein_enriched": { "function": "Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development", "gene_name": "Adgre1", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q61549" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation affects TNF\u03b1 secretion and stability.", "mechanism": "TNF\u03b1 expression increased in alcohol/HFD, drives hepatic inflammation.", "protein": "TNF\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation modulates chemokine-receptor interactions.", "mechanism": "Ccl2 upregulated in alcohol/HFD, recruits monocytes to liver.", "protein": "Ccl2 (MCP-1)", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ion", "gene_name": "Ccl2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P10148" }, "relationship_type": "causal", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation critical for collagen stability and ECM deposition.", "mechanism": "Col3a1 expression increased in HFD+EtOH, marks fibrotic progression.", "protein": "Col3a1", "relationship_type": "biomarker", "source_pmcid": "PMC12693642" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect cytoskeletal assembly.", "mechanism": "Acta2 upregulated in HFD+EtOH, indicates activated stellate cells/fibrosis.", "protein": "Acta2 (\u03b1-SMA)", "protein_enriched": { "function": "Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells", "gene_name": "Acta2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G76370VV", "G49108TO" ], "uniprot_id": "P62737" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates TIMP1 secretion and activity.", "mechanism": "Timp1 upregulated in HFD+EtOH, inhibits matrix degradation, promotes fibrosis.", "protein": "Timp1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "Timp1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G25079LO" ], "uniprot_id": "P12032" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693642" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation modulates CD36 trafficking and lipid binding.", "mechanism": "Alcohol increases CD36 expression, promoting hepatic lipid uptake and steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12693642" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "O-GlcNAc modification regulates nuclear protein function in inflammation.", "mechanism": "Reduced glutamine lowers O-GlcNAcylation, exacerbating inflammation.", "protein": "O-GlcNAc-modified nuclear proteins", "relationship_type": "causal", "source_pmcid": "PMC12693642" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation affects Srebp1c maturation and activity.", "mechanism": "Alcohol upregulates Srebp1c, increasing lipid synthesis and steatosis.", "protein": "Srebp1c", "protein_enriched": { "function": "Apoptosis regulator that functions through different apoptotic signaling pathways (PubMed:23429263, PubMed:26015568, PubMed:26949185, PubMed:27098698, PubMed:9535847). Plays a roles as pro-apoptotic p", "gene_name": "Bok", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O35425" }, "relationship_type": "causal", "source_pmcid": "PMC12693642" }, { "confidence": "high", "disease": "Spinocerebellar ataxia", "glycan_involvement": "PMCA3 is a glycoprotein; glycosylation may affect folding and trafficking, but direct involvement in this disease is not specified.", "mechanism": "CaMBD mutation (G1107D) impairs CaM-dependent activation, reducing Ca2+ extrusion and disrupting neuronal Ca2+ homeostasis.", "protein": "Plasma Membrane Ca2+-ATPase 3 (PMCA3)", "protein_enriched": { "function": "ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:15", "gene_name": "ATP2C2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O75185" }, "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "high", "disease": "Congenital cerebellar ataxia", "glycan_involvement": "PMCA2 is glycosylated; glycosylation may modulate stability, but direct role in disease not detailed.", "mechanism": "CaMBD mutation (V1143F) weakens CaM binding, compromising Ca2+ extrusion in neurons.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "medium", "disease": "Deafness", "glycan_involvement": "Glycosylation may affect PMCA2 localization in auditory cells.", "mechanism": "Mutations near CaMBD (e.g., V1113G, T1086D) disrupt Ca2+ regulation in cochlear hair cells.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "medium", "disease": "Intellectual developmental disorder", "glycan_involvement": "Glycosylation may influence PMCA2 function in neurons.", "mechanism": "Missense/frameshift variants near CaMBD impair neuronal Ca2+ signaling.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "medium", "disease": "Epileptic encephalopathy", "glycan_involvement": "Glycosylation may affect PMCA2 stability and trafficking.", "mechanism": "Variants in ATP2B2 gene affect Ca2+ extrusion, contributing to neuronal hyperexcitability.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "medium", "disease": "Aldosterone-producing adrenal cortical adenoma", "glycan_involvement": "Glycosylation may affect PMCA3 function in adrenal tissue.", "mechanism": "Somatic deletions in PMCA3 impair Ca2+ coordination, leading to autonomous aldosterone secretion.", "protein": "Plasma Membrane Ca2+-ATPase 3 (PMCA3)", "protein_enriched": { "function": "ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:15", "gene_name": "ATP2C2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O75185" }, "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "low", "disease": "Muscle hypotonia", "glycan_involvement": "Glycosylation may modulate PMCA3 activity in muscle.", "mechanism": "ATP2B3 variants disrupt Ca2+ homeostasis in muscle cells.", "protein": "Plasma Membrane Ca2+-ATPase 3 (PMCA3)", "protein_enriched": { "function": "ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:15", "gene_name": "ATP2C2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O75185" }, "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "medium", "disease": "Malignant neoplasm of prostate", "glycan_involvement": "Glycosylation may influence PMCA4 stability and cell surface expression.", "mechanism": "PMCA4 expression modulates cell migration and metastasis; altered CaMBD may affect cancer progression.", "protein": "Plasma Membrane Ca2+-ATPase 4 (PMCA4)", "protein_enriched": { "function": "Polymerizes (R)-3-hydroxybutyryl-CoA to create polyhydroxybutyrate (PHB) which consists of thousands of hydroxybutyrate molecules linked end to end. PHB serves as an intracellular energy reserve mater", "gene_name": "phaC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P23608" }, "relationship_type": "modifier/therapeutic_target", "source_pmcid": "PMC12693652" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Glycosylation may affect PMCA2 function in the brain.", "mechanism": "ATP2B2 variants affect neuronal Ca2+ signaling, contributing to neurodevelopmental phenotypes.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "low", "disease": "Dystonia", "glycan_involvement": "Glycosylation may modulate PMCA2 activity.", "mechanism": "ATP2B2 mutations impair Ca2+ extrusion in motor neurons.", "protein": "Plasma Membrane Ca2+-ATPase 2 (PMCA2)", "relationship_type": "causal", "source_pmcid": "PMC12693652" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation affects LRG stability and detection in serum assays.", "mechanism": "Serum LRG levels correlate with endoscopic inflammation in CD.", "protein": "Leucine-rich alpha-2-glycoprotein (LRG)", "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "N-glycosylation modulates CRP's serum half-life and immunoreactivity.", "mechanism": "Elevated CRP indicates active inflammation but is less sensitive for early POR.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Glycosylation influences FC's stability in fecal samples.", "mechanism": "Elevated FC (>150 \u00b5g/g) predicts early recurrence post-surgery.", "protein": "Fecal calprotectin (FC)", "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "medium", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Glycosylation may affect chemokine-receptor interactions.", "mechanism": "Serum CXCL9 is a robust predictor of POR via CXCR3 axis activation.", "protein": "CXCL9", "protein_enriched": { "function": "Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3", "gene_name": "CXCL9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07325" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "medium", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Glycosylation modulates chemokine activity and stability.", "mechanism": "Serum CXCL11 predicts POR; involved in innate immune pathways.", "protein": "CXCL11", "protein_enriched": { "function": "Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes. Induces calcium release in activated T-cells. Binds to CXCR3. May play an important role in CNS di", "gene_name": "CXCL11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "medium", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "N-glycosylation regulates MMP1 secretion and activity.", "mechanism": "Serum MMP1 is a predictor of POR, reflecting tissue remodeling.", "protein": "Matrix metalloproteinase-1 (MMP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Fc glycosylation affects antibody effector function and pharmacokinetics.", "mechanism": "Anti-TNF monoclonal antibody reduces endoscopic recurrence post-surgery.", "protein": "Infliximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Fc glycosylation modulates antibody stability and immune response.", "mechanism": "Anti-TNF monoclonal antibody prevents POR, especially in high-risk patients.", "protein": "Adalimumab", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Glycosylation of IgG1 backbone influences pharmacodynamics.", "mechanism": "Blocks \u03b14\u03b27 integrin, reducing gut lymphocyte trafficking and POR.", "protein": "Vedolizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693668" }, { "confidence": "medium", "disease": "Postoperative recurrence (POR) of Crohn's disease", "glycan_involvement": "Fc glycosylation impacts antibody function and half-life.", "mechanism": "Blocks IL-12/23 pathway, reducing mucosal inflammation and POR.", "protein": "Ustekinumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693668" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Aberrant sialylation of glycoproteins", "mechanism": "Over-sialylation leads to increased interaction with Siglecs, suppressing immune response against cancer cells.", "protein": "Cell surface glycoproteins (sialylated)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "Immune checkpoint suppression", "glycan_involvement": "Recognition of sialic acid residues on glycoproteins", "mechanism": "Siglecs bind sialylated glycoproteins on cancer cells, inhibiting immune cell activation.", "protein": "Siglecs", "relationship_type": "causal", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "Tay-Sachs disease", "glycan_involvement": "Failure to degrade \u03b2-N-acetyl-hexosamine-containing glycoproteins/glycolipids", "mechanism": "Deficiency leads to impaired catabolism of GM2 ganglioside, causing neurodegeneration.", "protein": "\u03b2-N-acetyl-hexosaminidase", "relationship_type": "causal", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "Sandhoff disease", "glycan_involvement": "Impaired degradation of glycosylated gangliosides", "mechanism": "Deficiency leads to GM2 accumulation and lysosomal dysfunction.", "protein": "\u03b2-N-acetyl-hexosaminidase", "relationship_type": "causal", "source_pmcid": "PMC12693669" }, { "confidence": "medium", "disease": "Tay-Sachs disease", "glycan_involvement": "Transfers GalNAc to ganglioside precursors", "mechanism": "Enzyme responsible for GM2 biosynthesis; potential target for modulating GM2 levels.", "protein": "B4GALNT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "Tay-Sachs disease", "glycan_involvement": "GM2 is a glycosylated lipid accumulating due to enzyme deficiency", "mechanism": "Accumulation in neurons leads to cell damage and neurological symptoms.", "protein": "Ganglioside GM2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693669" }, { "confidence": "medium", "disease": "Brucellosis", "glycan_involvement": "Hexasaccharide epitopes on glycoprotein", "mechanism": "O-antigen glycoprotein recognized by antibodies; target for vaccine design.", "protein": "Brucella O-antigen", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "medium", "disease": "Bacterial meningitis (Neisseria meningitidis)", "glycan_involvement": "Sialylation of capsule and lipooligosaccharides", "mechanism": "CSS essential for sialylation of bacterial surface, enabling immune evasion.", "protein": "CMP-sialic acid synthetase (CSS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "Gram-negative bacterial sepsis", "glycan_involvement": "Glucosamine-based glycolipid core", "mechanism": "Lipid A triggers strong immune response and toxicity.", "protein": "Lipid A (LPS core)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "medium", "disease": "Bacterial infection (general)", "glycan_involvement": "Recognition of mannosylated glycoproteins", "mechanism": "FimH binds mannosylated glycoproteins for bacterial adhesion; inhibition prevents infection.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693669" }, { "confidence": "high", "disease": "HFpEF", "glycan_involvement": "Binds \u03b2-galactoside glycans on ECM proteins, mediates fibrotic remodeling.", "mechanism": "Elevated Galectin-3 reflects myocardial fibrosis and inflammation, correlates with disease severity and adverse outcomes.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "high", "disease": "HFpEF", "glycan_involvement": "Heavily glycosylated extracellular domain; glycosylation affects stability and function.", "mechanism": "sST2 levels rise with myocardial stretch and inflammation, predict mortality and rehospitalization.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "high", "disease": "HFpEF", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated GDF-15 indicates systemic stress, mitochondrial dysfunction, and predicts HF progression.", "protein": "GDF-15", "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Multiple N-glycosylation sites; glycosylation modulates receptor-ligand interactions.", "mechanism": "Circulating sLRP1 correlates with epicardial adipose tissue volume and metabolic dysfunction.", "protein": "sLRP1", "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "high", "disease": "Coronary Artery Disease", "glycan_involvement": "O-glycosylation at collagenous domain required for multimerization and activity.", "mechanism": "Reduced adiponectin from EAT is associated with increased inflammation and cardiovascular risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12693676" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "N-glycosylation affects secretion and receptor binding.", "mechanism": "Elevated leptin in EAT promotes oxidative stress and myocardial injury.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12693676" }, { "confidence": "medium", "disease": "HFpEF", "glycan_involvement": "Predicted N-glycosylation; functional impact not detailed.", "mechanism": "Increased resistin in EAT and plasma reflects local inflammation, associated with HF severity.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "medium", "disease": "HFpEF", "glycan_involvement": "No glycosylation specified.", "mechanism": "Reduced apelin in EAT and plasma linked to adverse remodeling; apelin counteracts resistin-induced hypertrophy.", "protein": "Apelin", "relationship_type": "protective", "source_pmcid": "PMC12693676" }, { "confidence": "high", "disease": "Obesity-related Cardiac Dysfunction", "glycan_involvement": "N-glycosylation required for secretion and bioactivity.", "mechanism": "Elevated IL-6 from EAT drives local inflammation, arterial stiffness, and impaired myocardial function.", "protein": "Interleukin-6", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693676" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "ApoB-100 is N-glycosylated; glycosylation affects LDL particle properties.", "mechanism": "Small dense LDL particles associated with increased EAT volume and cardiometabolic risk.", "protein": "LDL (ApoB-100)", "relationship_type": "biomarker", "source_pmcid": "PMC12693676" }, { "confidence": "high", "disease": "Coronary Slow Flow (CSF)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function as an inflammatory marker.", "mechanism": "Elevated CRP indicates systemic inflammation, which is implicated in CSF pathogenesis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Chest Pain", "glycan_involvement": "Glycosylation modulates CRP's plasma half-life and detection.", "mechanism": "High CRP levels correlate with inflammatory chest pain presentations.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Malignant Ventricular Arrhythmias", "glycan_involvement": "Glycosylation may influence CRP's interaction with immune cells.", "mechanism": "Inflammation (high CRP) is associated with arrhythmogenic risk in CSF patients.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Sudden Cardiac Death", "glycan_involvement": "Glycosylation impacts CRP's role in acute-phase response.", "mechanism": "Elevated CRP is linked to increased risk of sudden cardiac death in CSF.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "high", "disease": "Coronary Slow Flow (CSF)", "glycan_involvement": "Albumin glycosylation affects its antioxidant and transport functions.", "mechanism": "Low albumin (negative acute-phase reactant) in CRP/albumin ratio enhances CSF prediction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "high", "disease": "Coronary Slow Flow (CSF)", "glycan_involvement": "Both proteins are glycosylated; ratio reflects combined glycoprotein acute-phase response.", "mechanism": "High CRP/albumin ratio is a robust indicator of inflammation and CSF risk.", "protein": "CRP/albumin ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Coronary Slow Flow (CSF)", "glycan_involvement": "ET-1 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Elevated ET-1 causes microvascular vasoconstriction, contributing to CSF.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal", "source_pmcid": "PMC12693680" }, { "confidence": "low", "disease": "Malignant Ventricular Arrhythmias", "glycan_involvement": "Glycosylation modulates ET-1 bioactivity.", "mechanism": "High ET-1 promotes arrhythmogenic microvascular dysfunction.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Chest Pain", "glycan_involvement": "Glycosylation influences albumin's anti-inflammatory properties.", "mechanism": "Low albumin levels (as part of CRP/albumin ratio) indicate inflammatory chest pain.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "medium", "disease": "Sudden Cardiac Death", "glycan_involvement": "Reflects combined glycoprotein acute-phase response.", "mechanism": "High ratio predicts increased risk of sudden cardiac death in CSF.", "protein": "CRP/albumin ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12693680" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Removes O-GlcNAc from proteins, affecting glycosylation-dependent signaling.", "mechanism": "Modulates histone acetylation via O-GlcNAcylation crosstalk, influences p53 stability and platinum resistance.", "protein": "OGA (O-GlcNAcase)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12693745" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Binds acetylated lysines, indirectly affected by glycosylation status of histones.", "mechanism": "Acts as a reader of acetylated histones, enhances transcription of oncogenes, targeted by inhibitors.", "protein": "BRD4", "protein_enriched": { "function": "Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation (PubMed:20871596, Pu", "gene_name": "BRD4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O60885" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12693745" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "May be glycosylated, affecting nuclear localization and coactivator function.", "mechanism": "Coactivator linked to platinum resistance and poor prognosis.", "protein": "NCOA3", "protein_enriched": { "function": "Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactiv", "gene_name": "NCOA3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G93422ZO", "G49108TO" ], "uniprot_id": "Q9Y6Q9" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12693745" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate HDAC1 stability and activity.", "mechanism": "Overexpression leads to abnormal histone acetylation, silencing tumor suppressor genes.", "protein": "HDAC1", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:16762839, PubMed:17704056, PubMed:28497810). Histone d", "gene_name": "HDAC1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13547" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12693745" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Potential glycosylation affects enzymatic activity.", "mechanism": "Altered activity influences drug sensitivity and tumor progression.", "protein": "HDAC11", "protein_enriched": { "function": "Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an importa", "gene_name": "HDAC11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96DB2" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12693745" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may modulate deacetylase activity.", "mechanism": "Associated with favorable prognosis; regulates histone acetylation.", "protein": "SIRT5", "protein_enriched": { "function": "NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693", "gene_name": "SIRT5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NXA8" }, "relationship_type": "protective", "source_pmcid": "PMC12693745" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "No direct glycosylation, but m6A modification interacts with glycoprotein signaling.", "mechanism": "Overexpression enhances cell proliferation and chemotherapy resistance via m6A RNA methylation.", "protein": "METTL3", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, di", "gene_name": "METTL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U44" }, "relationship_type": "causal", "source_pmcid": "PMC12693745" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "No direct glycosylation, but impacts glycoprotein expression via RNA regulation.", "mechanism": "Demethylates m6A/m6Am RNA, connects metabolic status (obesity) with cancer susceptibility.", "protein": "FTO", "protein_enriched": { "function": "RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:220027", "gene_name": "FTO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9C0B1" }, "relationship_type": "causal", "source_pmcid": "PMC12693745" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect protein stability and RNA binding.", "mechanism": "m6A reader, regulates translation of oncogenic mRNAs.", "protein": "YTHDF1", "protein_enriched": { "function": "Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability (PubMed:24284625, PubMed:26318451, PubMed:32492408, PubMed:39900921). M6A is a modification p", "gene_name": "YTHDF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9BYJ9" }, "relationship_type": "causal", "source_pmcid": "PMC12693745" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Removes O-GlcNAc, regulating glycosylation-dependent transcription.", "mechanism": "Modulates histone acetylation and p53 stability, affecting tumor progression.", "protein": "OGA (O-GlcNAcase)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12693745" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "IL-6 is glycosylated, affecting stability and secretion.", "mechanism": "Elevated hepatic IL-6 expression drives inflammation and progression of NASH; PCP reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693755" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "Increased IL-1\u03b2 promotes hepatic inflammation; PCP lowers IL-1\u03b2 expression.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693755" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation influences TNF-\u03b1 receptor binding.", "mechanism": "TNF-\u03b1 upregulation contributes to liver injury and fibrosis; PCP reduces TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693755" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation affects cytokine secretion.", "mechanism": "IL-18 promotes hepatic inflammation; PCP intervention lowers IL-18.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693755" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "FGF21 is glycosylated, affecting receptor interaction.", "mechanism": "PCP-induced SCFAs activate FGF21/PI3K/AKT pathway, reducing insulin resistance.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12693755" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates Smad7 stability.", "mechanism": "Upregulation of Smad7 by plant polysaccharides inhibits TGF-\u03b2/Smad signaling, preventing fibrosis.", "protein": "Smad7", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12693755" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "PCP suppresses COX-2, reducing inflammation.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693755" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Taurocholate is a glyco-conjugate (taurine conjugation).", "mechanism": "Taurocholate normalization by PCP improves lipid metabolism and reduces hepatic injury.", "protein": "Taurocholate (bile acid conjugate)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12693755" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b2 receptor binding.", "mechanism": "TGF-\u03b2 signaling drives fibrosis; Smad7 upregulation inhibits this pathway.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12693755" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "PCP suppresses iNOS, reducing oxidative stress and inflammation.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693755" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Calprotectin is glycosylated, affecting its stability and detection.", "mechanism": "Fecal calprotectin levels indicate micro-inflammation in the colon.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "high", "disease": "Metabolic Syndrome", "glycan_involvement": "Ferritin glycosylation modulates its serum half-life and immunogenicity.", "mechanism": "Serum ferritin reflects subclinical inflammation associated with metabolic syndrome.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "CRP glycosylation affects its binding to ligands and immune function.", "mechanism": "Elevated hsCRP is a marker of systemic inflammation and cardiovascular risk.", "protein": "High-sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "SREBP-1 glycosylation regulates its nuclear translocation and activity.", "mechanism": "SCFA-induced activation of SREBP-1 promotes hepatic lipogenesis, increasing adiposity.", "protein": "SREBP-1", "relationship_type": "causal", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation modulates SREBP-1 stability and function.", "mechanism": "Propionate/acetate from Veillonella activates SREBP-1, elevating triglycerides.", "protein": "SREBP-1", "relationship_type": "causal", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Bacterial glycoproteins mediate host-microbe interactions and immune modulation.", "mechanism": "Veillonella abundance increases SCFA production, enhancing energy harvest and adiposity.", "protein": "Veillonella surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Bacterial glycoproteins influence butyrate delivery and anti-inflammatory signaling.", "mechanism": "Marvinbryantia produces butyrate, supporting colonocyte health and lipid-lowering effects.", "protein": "Marvinbryantia surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation affects calprotectin\u2019s immunoreactivity.", "mechanism": "Fecal calprotectin may reflect gut inflammation linked to metabolic syndrome.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "CRP glycosylation impacts its inflammatory signaling.", "mechanism": "hsCRP levels correlate with metabolic risk and inflammation.", "protein": "High-sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates ferritin\u2019s clearance and immune recognition.", "mechanism": "Elevated ferritin is associated with increased cardiovascular risk due to inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693806" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "IRS1 is a glycoprotein; glycosylation may affect stability and signaling.", "mechanism": "SGB121 and F1 restore IRS1 phosphorylation, improving insulin signaling and glucose uptake.", "protein": "Insulin Receptor Substrate 1 (IRS1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693820" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "GLUT2 is N-glycosylated; glycosylation is essential for membrane localization.", "mechanism": "SGB121 and F1 upregulate GLUT2 expression, enhancing hepatic glucose uptake.", "protein": "Glucose Transporter 2 (GLUT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693820" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "SREBP1 is glycosylated; glycosylation may regulate its stability and activity.", "mechanism": "SREBP1 upregulation drives lipogenesis and hepatic lipid accumulation.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "causal", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Not a classical glycoprotein; indirect glycan effects possible.", "mechanism": "PPAR\u03b1 activation promotes \u03b2-oxidation, reducing hepatic lipid content.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Akt is not a glycoprotein; no direct glycan involvement.", "mechanism": "SGB121 and F1 enhance Akt phosphorylation, improving insulin signaling.", "protein": "Akt", "protein_enriched": { "function": "AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, gro", "gene_name": "Akt1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47196" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "AMPK is not a glycoprotein; no direct glycan involvement.", "mechanism": "AMPK activation by F1 suppresses lipogenesis and promotes fatty acid oxidation.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "FAS is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "FAS upregulation increases fatty acid synthesis, contributing to steatosis.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "ACC is glycosylated; glycosylation may modulate its function.", "mechanism": "ACC activity promotes malonyl-CoA production and lipogenesis.", "protein": "ACC", "relationship_type": "causal", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "CPT1 is glycosylated; glycosylation may affect mitochondrial targeting.", "mechanism": "CPT1 upregulation enhances mitochondrial fatty acid oxidation, reducing steatosis.", "protein": "CPT1", "relationship_type": "protective", "source_pmcid": "PMC12693820" }, { "confidence": "medium", "disease": "Oxidative Stress-Related Liver Injury", "glycan_involvement": "NRF2 is not a glycoprotein; no direct glycan involvement.", "mechanism": "F1 activates NRF2, upregulating antioxidant enzymes and reducing oxidative damage.", "protein": "NRF2", "relationship_type": "protective", "source_pmcid": "PMC12693820" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ATX is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Serum ATX levels are elevated in MASLD and correlate with disease severity and progression.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693944" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation supports ATX secretion and function in the extracellular matrix.", "mechanism": "ATX generates LPA, which activates hepatic stellate cells and promotes fibrogenesis.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "causal", "source_pmcid": "PMC12693944" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation is essential for ATX secretion from adipocytes.", "mechanism": "Obese adipocytes overexpress ATX, increasing LPA and promoting inflammation and adipogenesis.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "Metabolic inflammation", "glycan_involvement": "Glycosylation affects ATX stability and extracellular signaling.", "mechanism": "ATX-LPA axis drives systemic inflammation via immune cell recruitment.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for ATX enzymatic activity.", "mechanism": "LPA generated by ATX impairs insulin signaling in liver and adipose tissue.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "causal", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation supports ATX function in tumor microenvironment.", "mechanism": "ATX-LPA signaling promotes carcinogenesis in chronic liver disease.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation maintains ATX circulatory half-life.", "mechanism": "Elevated ATX/LPA levels are associated with increased cardiovascular risk in MASLD.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12693944" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation status may affect ATX responsiveness to diet.", "mechanism": "Dietary intervention reduces ATX, improving liver and metabolic parameters.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for ATX secretion and inhibition.", "mechanism": "Pharmacological or nutritional inhibition of ATX reduces fibrosis progression.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12693944" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Sex differences may influence ATX glycosylation and secretion.", "mechanism": "Greater ATX reduction in women, possibly due to estrogen-mediated regulation and adipose distribution.", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "sex-specific modulation", "source_pmcid": "PMC12693944" }, { "confidence": "high", "disease": "Drug intoxication", "glycan_involvement": "N-glycosylation affects trafficking and function.", "mechanism": "Efflux transporter reduces intracellular drug accumulation, protecting against toxicity.", "protein": "ABCB1A (P-glycoprotein)", "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "Downregulation impairs phospholipid transport, increasing risk of cholestatic liver injury.", "protein": "ABCB4 (MDR3)", "relationship_type": "causal", "source_pmcid": "PMC12694059" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "N-glycosylation stabilizes extracellular activity.", "mechanism": "Detoxifies hydrogen peroxide, reducing oxidative damage.", "protein": "GPX3", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione", "gene_name": "GPX3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22352" }, "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "N-glycosylation modulates secretion and activity.", "mechanism": "Reduces lipid peroxides, protecting tissues from oxidative injury.", "protein": "GPX5", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-l", "gene_name": "Gpx5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30710" }, "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "high", "disease": "Drug intoxication", "glycan_involvement": "Glycosylation influences stability and activity.", "mechanism": "Conjugates toxic metabolites for excretion.", "protein": "GSTT1", "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "Glycosylation affects enzyme efficiency.", "mechanism": "Detoxifies electrophilic compounds, reducing metabolic stress.", "protein": "GSTM1", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prost", "gene_name": "GSTM1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09488" }, "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Foetal skeletal malformation", "glycan_involvement": "N-glycosylation required for proper folding and activity.", "mechanism": "Regulates vitamin D activation; downregulation may impair bone mineralization.", "protein": "CYP27B1", "relationship_type": "causal", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation modulates membrane association.", "mechanism": "Maintains redox balance, protecting hepatocytes.", "protein": "CYB5R3", "protein_enriched": { "function": "Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor", "gene_name": "CYB5R3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P00387" }, "relationship_type": "protective", "source_pmcid": "PMC12694059" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Regulates glycolytic flux; downregulation may impair energy metabolism.", "protein": "PKM", "relationship_type": "causal", "source_pmcid": "PMC12694059" }, { "confidence": "low", "disease": "Addiction", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Modulates endocannabinoid signaling; altered activity may affect addiction pathways.", "protein": "FAA H", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694059" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "HDL is a glycoprotein; glycosylation affects its function and clearance.", "mechanism": "Lower HDL cholesterol associated with irregular sleep and increased cardiometabolic risk.", "protein": "HDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC12694086" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Lipoproteins are glycosylated; glycan patterns modulate lipid metabolism.", "mechanism": "Higher total cholesterol linked to poor sleep regularity and increased fat mass.", "protein": "Total cholesterol (LDL/HDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12694086" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Homocysteine metabolism involves glycoproteins; altered glycosylation may affect clearance.", "mechanism": "Elevated homocysteine in short sleep duration; risk factor for vascular disease.", "protein": "Homocysteine", "relationship_type": "biomarker", "source_pmcid": "PMC12694086" }, { "confidence": "medium", "disease": "Sleep disturbance", "glycan_involvement": "Folate-binding protein is glycosylated; glycan status may affect folate transport.", "mechanism": "Lower serum folate associated with irregular sleep; impacts one-carbon metabolism and neurotransmitter synthesis.", "protein": "Folate-binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC12694086" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin is glycosylated; glycosylation modulates receptor binding.", "mechanism": "Sleep deprivation reduces leptin, increasing appetite and fat mass.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Ghrelin is glycosylated; glycan modifications affect stability.", "mechanism": "Short sleep increases ghrelin, promoting hunger and weight gain.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Insulin glycosylation affects receptor interaction and clearance.", "mechanism": "Sleep deprivation impairs insulin sensitivity, increasing diabetes risk.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "ABCA1 is glycosylated; glycosylation influences lipid transport.", "mechanism": "Circadian misalignment disrupts ABCA1 expression, affecting HDL assembly.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "SREBP-1c is glycosylated; glycan status may regulate activity.", "mechanism": "Irregular sleep alters SREBP-1c, impacting cholesterol biosynthesis.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "HMG-CoA reductase is glycosylated; glycosylation modulates enzyme stability.", "mechanism": "Circadian disruption affects HMG-CoA reductase, altering cholesterol synthesis.", "protein": "HMG-CoA reductase", "protein_enriched": { "function": "Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in c", "gene_name": "HMGCR", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G46503DX", "G48584BU", "G62765YT", "G64527OM", "G70101JE", "G49108TO", "G80920RR" ], "uniprot_id": "P04035" }, "relationship_type": "causal", "source_pmcid": "PMC12694086" }, { "confidence": "high", "disease": "Coffee leaf rust", "glycan_involvement": "Hydroxyproline-rich glycoproteins are extensively O-glycosylated, which is essential for cell wall structure and defense", "mechanism": "Strengthens cell wall, limiting pathogen ingress", "protein": "Hydroxyproline-rich glycoprotein family protein", "relationship_type": "protective", "source_pmcid": "PMC12694222" }, { "confidence": "high", "disease": "Coffee leaf rust", "glycan_involvement": "N-glycosylation required for proper folding and cell surface localization", "mechanism": "Recognizes fungal chitin, triggers immune signaling", "protein": "Chitin elicitor receptor kinase 1 (CERK1)", "relationship_type": "causal", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Coffee leaf rust", "glycan_involvement": "Glycosylation stabilizes secreted peroxidase activity", "mechanism": "Generates reactive oxygen species, reinforces cell wall during defense", "protein": "Peroxidase", "relationship_type": "protective", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Coffee leaf rust", "glycan_involvement": "Glycosylation may affect receptor stability and signaling", "mechanism": "Functions as immune receptor, triggers defense upon pathogen detection", "protein": "NB-ARC domain-containing protein", "relationship_type": "causal", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Coffee leaf rust", "glycan_involvement": "N-glycosylation may be required for receptor function", "mechanism": "Pathogen recognition and defense activation", "protein": "RPP13-like protein", "relationship_type": "causal", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Coffee leaf rust", "glycan_involvement": "Potential O-glycosylation modulates nuclear localization and activity", "mechanism": "Regulates transcription of defense genes", "protein": "WRKY domain-containing protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694222" }, { "confidence": "low", "disease": "Coffee leaf rust", "glycan_involvement": "Glycosylation may influence E3 ligase stability", "mechanism": "Regulates protein turnover in defense signaling", "protein": "RING-type domain-containing protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694222" }, { "confidence": "high", "disease": "Coffee leaf rust", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity", "mechanism": "Degrades fungal cell wall chitin, limiting infection", "protein": "Chitinase", "relationship_type": "protective", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Yield reduction", "glycan_involvement": "O-glycosylation critical for cell wall extensibility", "mechanism": "Cell wall integrity affects fruit development and yield", "protein": "Hydroxyproline-rich glycoprotein family protein", "relationship_type": "causal", "source_pmcid": "PMC12694222" }, { "confidence": "medium", "disease": "Yield reduction", "glycan_involvement": "Likely O-glycosylated, impacting cell wall function", "mechanism": "Involved in cell wall modification, influencing bean size and yield", "protein": "TORTIFOLIA1-like protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12694222" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "Transferrin is N-glycosylated, affecting its stability and iron-binding capacity.", "mechanism": "Higher transferrin levels are associated with increased AD severity (EASI, SCORAD scores).", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "sTfR is N-glycosylated, influencing its solubility and detection.", "mechanism": "Elevated sTfR indicates functional iron deficiency and is negatively associated with AD severity.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Hepcidin is a glycopeptide; glycosylation may affect secretion and stability.", "mechanism": "Hepcidin regulates iron homeostasis; its levels are modulated by inflammation in AD.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Ferritin is glycosylated, impacting its serum half-life.", "mechanism": "Low ferritin is prevalent in AD, indicating iron deficiency.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "N-glycosylation modulates transferrin receptor binding.", "mechanism": "Transferrin increases in iron deficiency to enhance iron transport.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "N-glycosylation affects sTfR release and detection.", "mechanism": "sTfR rises in iron deficiency, reflecting increased cellular iron demand.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "CRP is N-glycosylated, influencing its immune recognition.", "mechanism": "Elevated CRP indicates systemic inflammation in AD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "IgE is heavily glycosylated, affecting receptor binding and immune activation.", "mechanism": "High IgE levels are associated with increased AD severity and impaired quality of life.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "IL-6 glycosylation modulates receptor interaction and signaling.", "mechanism": "IL-6 induces hepcidin, leading to iron sequestration and functional iron deficiency in AD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12694464" }, { "confidence": "medium", "disease": "Anemia of Inflammation", "glycan_involvement": "N-glycosylation is essential for TfR1 function and sTfR generation.", "mechanism": "TfR1 mediates cellular iron uptake; its soluble form (sTfR) reflects iron demand in inflammation.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12694464" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S-RBD modulates antigenicity and immune recognition.", "mechanism": "S-RBD is the primary target for neutralising antibodies elicited by vaccination, blocking viral entry.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694603" }, { "confidence": "high", "disease": "SARS-like Betacoronavirus Infection", "glycan_involvement": "Glycan shield affects breadth of antibody response.", "mechanism": "Cross-reactive antibodies to S-RBD provide protection against diverse sarbecoviruses.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694603" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Membrane anchoring may influence glycosylation pattern and immunogenicity.", "mechanism": "Membrane-anchored S-RBD-TM delivered by influenza vector induces robust neutralising antibody response.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD-TM)", "relationship_type": "protective", "source_pmcid": "PMC12694603" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Secretory form may have altered glycosylation affecting immunogenicity.", "mechanism": "Secretory form of S-RBD elicits neutralising antibodies, but less robust than TM form.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD-Sec)", "relationship_type": "protective", "source_pmcid": "PMC12694603" }, { "confidence": "medium", "disease": "SARS-like Betacoronavirus Infection", "glycan_involvement": "Glycosylation differences between clades may affect cross-reactivity.", "mechanism": "Prime-boost with S-RBD-TM BM48-31 broadens antibody response to distant sarbecoviruses.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD-TM BM48-31)", "relationship_type": "protective", "source_pmcid": "PMC12694603" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry into host cells.", "protein": "Influenza A Haemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC12694603" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "S-RBD is used as a biomarker for serological detection of infection and immunity.", "protein": "SARS-CoV-2 Spike Receptor Binding Domain (S-RBD)", "relationship_type": "biomarker", "source_pmcid": "PMC12694603" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "CA 19-9 is a sialylated glycan epitope on a glycoprotein, detected due to its aberrant glycosylation in cancer.", "mechanism": "Elevated serum CA 19-9 levels (>37 U/mL) are associated with tumor progression and poor prognosis.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12694677" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation pattern of CA 19-9 is not cancer-specific, leading to false positives.", "mechanism": "Moderately elevated CA 19-9 (100\u2013500 U/mL) can occur in benign inflammatory conditions.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12694677" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Glycosylation changes in hepatic disease can increase CA 19-9 release.", "mechanism": "CA 19-9 levels may rise in benign hepatic conditions due to altered glycoprotein secretion.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12694677" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Aberrant glycosylation increases CA 19-9 antigenicity.", "mechanism": "CA 19-9 is used for treatment monitoring and prognosis in pancreatic cancer.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12694677" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Extensive O-glycosylation of MUC4 affects its detection and function.", "mechanism": "MUC4 is a glycoprotein often upregulated in pancreatic cancer and may interfere with CA 19-9 detection.", "protein": "Mucin 4 (MUC4)", "relationship_type": "biomarker", "source_pmcid": "PMC12694677" }, { "confidence": "low", "disease": "Pancreatic cancer", "glycan_involvement": "Minor glycosylation; not directly relevant to CA 19-9 detection.", "mechanism": "HSA is a common serum protein; not a direct biomarker but can interfere with CA 19-9 assays.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker (interferent)", "source_pmcid": "PMC12694677" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Cancer-associated changes in glycosylation increase CA 19-9 expression.", "mechanism": "CA 19-9 is not causal but reflects underlying malignant transformation and altered glycosylation.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "causal (indirect)", "source_pmcid": "PMC12694677" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects processing and aggregation.", "mechanism": "A\u03b2 aggregation forms plaques, a hallmark of AD pathology.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12695547" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation propensity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to neurodegeneration.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12695547" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation of APP influences its cleavage and A\u03b2 generation.", "mechanism": "EVOO polyphenols (e.g., oleuropein, hydroxytyrosol) modulate APP processing, reducing A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "RAGE is N-glycosylated; glycosylation affects ligand binding and signaling.", "mechanism": "Oleuropein and oleocanthal inhibit RAGE/HMGB1 pathway, reducing neuroinflammation and A\u03b2 transport.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "LRP1 is heavily N-glycosylated; glycosylation is critical for trafficking and function.", "mechanism": "Oleocanthal upregulates LRP1, enhancing A\u03b2 clearance across the blood-brain barrier.", "protein": "LRP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "P-gp is N-glycosylated; glycosylation affects stability and localization.", "mechanism": "Oleocanthal increases P-gp expression, promoting A\u03b2 efflux from the brain.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE is O-glycosylated; glycosylation modulates lipid binding and receptor interactions.", "mechanism": "Oleocanthal activates ApoE-dependent A\u03b2 clearance pathways.", "protein": "ApoE", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "GLUT1 is N-glycosylated; glycosylation is essential for membrane localization.", "mechanism": "Oleocanthal prevents A\u03b2-induced downregulation of GLUT1, supporting neuronal glucose uptake.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695547" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "SNAP-25 is palmitoylated, not glycosylated; glycan involvement is minimal.", "mechanism": "Oleocanthal prevents A\u03b2-induced downregulation of SNAP-25, preserving synaptic function.", "protein": "SNAP-25", "relationship_type": "protective", "source_pmcid": "PMC12695547" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation.", "mechanism": "Tau aggregation is implicated in synucleinopathies; EVOO polyphenols inhibit tau and \u03b1-synuclein aggregation.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC12695547" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "FSHR is a glycoprotein receptor; glycosylation is essential for receptor folding and function.", "mechanism": "FSHR rs6166 Asn/Asn variant is associated with impaired osteogenic differentiation and lower bone mineral density, increasing osteoporosis risk.", "protein": "FSHR", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "FSH is a glycoprotein hormone; glycosylation required for secretion and receptor binding.", "mechanism": "Elevated FSH levels promote osteoclastogenesis and bone resorption, contributing to osteoporosis; anti-FSH antibody blocks bone loss.", "protein": "FSH", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "TSHR is a glycoprotein receptor; glycosylation affects receptor trafficking and function.", "mechanism": "TSHR rs1991517 Asp727Glu variant is associated with higher BMD and lower bone turnover, protective against osteoporosis.", "protein": "TSHR", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "TSH is a glycoprotein hormone; glycosylation required for activity.", "mechanism": "Low TSH (e.g., subclinical hyperthyroidism) increases osteoporosis risk; TSH inhibits osteoclastogenesis and promotes bone formation.", "protein": "TSH", "relationship_type": "protective/causal", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Osteoporosis-Pseudoglioma Syndrome (OPPG)", "glycan_involvement": "LRP5 is a glycoprotein receptor; glycosylation affects receptor stability.", "mechanism": "Loss-of-function mutations in LRP5 decrease Wnt signalling, causing early-onset osteoporosis and blindness.", "protein": "LRP5", "relationship_type": "causal", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "SOST is a glycoprotein; glycosylation affects secretion.", "mechanism": "Loss of sclerostin leads to unchecked bone formation; SOST inhibits Wnt/\u03b2-catenin signalling.", "protein": "SOST (Sclerostin)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12695586" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "ADRB2 is a glycoprotein receptor; glycosylation modulates receptor function.", "mechanism": "ADRB2 rs1042713 AA SNP is prevalent in osteoporotic patients; associated with impaired osteogenic differentiation.", "protein": "ADRB2", "relationship_type": "biomarker", "source_pmcid": "PMC12695586" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "FSHR glycosylation required for receptor function.", "mechanism": "FSHR rs6166 Ser/Ser variant may confer protection against obesity; impacts MSC fate toward adipogenesis.", "protein": "FSHR", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12695586" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "TSHR glycosylation affects receptor internalization.", "mechanism": "TSHR signalling via \u03b2-arrestin1 promotes osteoblast differentiation; \u03b2-arrestin pathway hyperactive in osteosarcoma.", "protein": "TSHR", "relationship_type": "biomarker", "source_pmcid": "PMC12695586" }, { "confidence": "medium", "disease": "Familial tooth agenesis", "glycan_involvement": "AXIN2 is not a glycoprotein; no direct glycan involvement.", "mechanism": "AXIN2 mutations stabilize \u03b2-catenin, leading to oral bone-specific syndrome and tooth agenesis.", "protein": "AXIN2", "relationship_type": "causal", "source_pmcid": "PMC12695586" }, { "confidence": "high", "disease": "Autoimmune encephalitis", "glycan_involvement": "IgG glycosylation modulates antibody effector functions and pathogenicity.", "mechanism": "Pathogenic IgG autoantibodies mediate neuronal damage.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Guillain\u2013Barr\u00e9 syndrome", "glycan_involvement": "Glycosylation affects IgG-mediated complement activation.", "mechanism": "Autoantibodies (IgG) target peripheral nerve components, causing demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorders", "glycan_involvement": "Fc glycan structure influences antibody pathogenicity.", "mechanism": "IgG autoantibodies (e.g., anti-AQP4) drive CNS demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12695613" }, { "confidence": "medium", "disease": "Chronic inflammatory demyelinating polyneuropathy", "glycan_involvement": "Altered glycosylation may affect antibody clearance and immune activation.", "mechanism": "IgG autoantibodies contribute to chronic nerve inflammation and demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Autoimmune encephalitis", "glycan_involvement": "Glycosylation status may affect detection and function.", "mechanism": "Presence of specific autoantibodies in serum/CSF indicates disease.", "protein": "Pathogenic autoantibodies (various IgG subclasses)", "relationship_type": "biomarker", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Guillain\u2013Barr\u00e9 syndrome", "glycan_involvement": "Glycan modifications influence antibody pathogenicity.", "mechanism": "Autoantibody titers correlate with disease activity.", "protein": "Pathogenic autoantibodies (various IgG subclasses)", "relationship_type": "biomarker", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorders", "glycan_involvement": "Fc glycosylation modulates effector functions.", "mechanism": "Anti-AQP4 IgG is diagnostic for NMOSD.", "protein": "Pathogenic autoantibodies (various IgG subclasses)", "relationship_type": "biomarker", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "Autoimmune neurological disorders (general)", "glycan_involvement": "Protein A adsorber binds Fc region, dependent on glycan structure.", "mechanism": "IA removes pathogenic IgG, reducing disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695613" }, { "confidence": "medium", "disease": "Autoimmune neurological disorders (general)", "glycan_involvement": "IVIG glycosylation affects anti-inflammatory properties.", "mechanism": "IVIG supplementation restores protective IgG levels after IA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12695613" }, { "confidence": "medium", "disease": "Autoimmune neurological disorders (general)", "glycan_involvement": "Glycosylation may affect IgG half-life and detection.", "mechanism": "Serum IgG levels monitor immunosuppression and treatment efficacy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12695613" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies target MOG, leading to CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12695702" }, { "confidence": "high", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition.", "mechanism": "Anti-MOG antibodies trigger inflammation and demyelination of optic nerve.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12695702" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation may influence MOG's immunogenicity.", "mechanism": "Anti-MOG antibodies implicated in ADEM pathogenesis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12695702" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "IL-6R is glycosylated; glycosylation affects receptor function and antibody binding.", "mechanism": "IL-6R blockade (tocilizumab) reduces inflammation and relapses in refractory MOGAD.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. 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May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12695702" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "CD44 glycosylation modulates binding affinity to P-selectin.", "mechanism": "Platelet P-selectin binds CD44 on leukemia cells, enhancing targeting and drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation of P-selectin required for ligand recognition.", "mechanism": "Platelet membrane P-selectin interacts with CD44 on AML cells for targeted nanoparticle delivery.", "protein": "P-selectin (CD62P)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Glycosylation maintains CD47 structure and function.", "mechanism": "Platelet membrane CD47 prevents phagocytosis, prolonging circulation of drug carriers.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). 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anti-PD-1 antibody delivery via platelets enhances immune response.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "CXCR4 glycosylation affects ligand binding and trafficking.", "mechanism": "CXCR4 mediates leukemia stem cell homing to bone marrow; targeted nanocarriers disrupt this axis.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "FLT3 glycosylation required for receptor maturation and signaling.", "mechanism": "FLT3-ITD mutation drives proliferation; antisense oligonucleotide delivery via RBC exosomes targets mutant FLT3.", "protein": "FLT3", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.", "gene_name": "FLT3", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P36888" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "CD33 glycosylation influences antibody and CAR recognition.", "mechanism": "CD33-targeted CAR-T and CAR-NK therapies selectively kill AML cells.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation modulates receptor stability and immune targeting.", "mechanism": "CD123-targeted CAR-NK and CAR-T therapies eliminate AML cells and leukemia stem cells.", "protein": "CD123 (IL3RA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "medium", "disease": "CML", "glycan_involvement": "CD26 glycosylation affects enzymatic activity and cell surface localization.", "mechanism": "CD26-targeted CAR-macrophages phagocytose CML-LSCs, overcoming TKI resistance.", "protein": "CD26 (DPP4)", "protein_enriched": { "function": "Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:172872", "gene_name": "DPP4", "glycan_count": 92, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G10019LZ", "G12793SR", "G13131HA", "G22310AV", "G30740WO", "G41882MT", "G48414YA", "G57776ZS", "G57888GL", "G62461SM", "G82348BZ", "G22768VO", "G42227JK", "G56014GC", "G81315DD", "G81980VO", "G06356OH", "G56784JY", "G00395TQ", "G01650EU", "G02815KT", "G02886BB", "G10486CT", "G27058EU", "G28681TP", "G37399XV", "G46691LC", "G59626AS", "G72747WU", "G87661QW", "G92050GC", "G00912UN", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G15664MX", "G18647XP", "G20210JR", "G23294PN", "G23719VF", "G23984SE", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G29299MO", "G31852PQ", "G31986NC", "G37881RL", "G38663NM", "G39446WN", "G41071NU", "G41247ZX", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G47644PP", "G47748JZ", "G50282JC", "G59924QI", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G70441OD", "G70619PT", "G77547TA", "G80920RR", "G83646BJ", "G85269DF", "G86182NS", "G87123QX", "G90382BL", "G90659AW", "G92275SC", "G95865ZB", "G96091TT", "G40926MX", "G68490OW", "G74724QE", "G79666IR", "G84225JN", "G84452RH", "G49108TO" ], "uniprot_id": "P27487" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "medium", "disease": "CLL", "glycan_involvement": "GP350 glycosylation required for CD21 binding and targeting specificity.", "mechanism": "GP350-anchored RBC exosomes deliver drugs to CD21+ B-CLL cells, inducing apoptosis.", "protein": "GP350 (EBV envelope)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695826" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "VEGF glycosylation modulates its stability and receptor binding.", "mechanism": "Silymarin inhibits VEGF, reducing angiogenesis and inflammation in psoriatic lesions.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "ICAM-1 N-glycosylation is critical for cell-cell interactions.", "mechanism": "Silymarin downregulates ICAM-1 expression, reducing leukocyte adhesion and tissue inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting secretion and receptor interaction.", "mechanism": "Silymarin suppresses TNF-\u03b1 production, reducing hepatic inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "TGF-\u03b21 glycosylation modulates its activation and signaling.", "mechanism": "Silymarin inhibits TGF-\u03b21, attenuating hepatic fibrosis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "IL-6 glycosylation affects its stability and bioactivity.", "mechanism": "Silymarin reduces IL-6, limiting tumor-promoting inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "CD80 N-glycosylation is essential for immune synapse formation.", "mechanism": "Silymarin downregulates CD80, suppressing T-cell activation.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "NLRP3 is glycosylated, influencing inflammasome assembly.", "mechanism": "Silymarin inhibits NLRP3 inflammasome activation, reducing renal inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 glycosylation affects its trafficking and function.", "mechanism": "Silymarin reduces A\u03b2 aggregation and toxicity without altering BACE1 activity.", "protein": "BACE1", "relationship_type": "biomarker", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "MMP glycosylation modulates enzyme activity and substrate specificity.", "mechanism": "Silymarin inhibits MMPs, preventing ECM degradation and skin lesion progression.", "protein": "MMPs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CD86 glycosylation is important for ligand binding and immune modulation.", "mechanism": "Silymarin downregulates CD86, reducing immune evasion and tumor progression.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695834" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "O-glycosylation required for selectin binding and T cell rolling.", "mechanism": "SELPLG downregulation or knockout in CAR T cells enhances in vitro migration into neuroblastoma tumor models.", "protein": "SELPLG (PSGL-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "O-glycosylation mediates selectin interactions for tissue entry.", "mechanism": "SELPLG deficiency increases T cell infiltration and activation in murine melanoma models.", "protein": "SELPLG (PSGL-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695837" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Glycosylation status affects selectin binding and migration.", "mechanism": "Low SELPLG expression marks CAR T cells with higher migratory capacity in vitro.", "protein": "SELPLG (PSGL-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Not glycosylated; acts via signaling pathways.", "mechanism": "High SH2D2A expression in CAR T cells correlates with increased migration and activation signatures in vitro.", "protein": "SH2D2A (TSAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "None.", "mechanism": "Upregulated in tumor-infiltrating T cells in ovarian cancer (public dataset analysis).", "protein": "SH2D2A (TSAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Renal cancer", "glycan_involvement": "None.", "mechanism": "Upregulated in tumor-infiltrating T cells in renal cancer (public dataset analysis).", "protein": "SH2D2A (TSAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "None.", "mechanism": "Upregulated in tumor-infiltrating T cells in multiple myeloma (public dataset analysis).", "protein": "SH2D2A (TSAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "None.", "mechanism": "Downregulated in tumor-infiltrating T cells in breast cancer (public dataset analysis).", "protein": "SH2D2A (TSAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12695837" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune recognition.", "mechanism": "Target antigen for CAR T cell therapy in neuroblastoma; glycosylation may affect antigenicity.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695837" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "O-glycosylation essential for selectin binding and migration regulation.", "mechanism": "SELPLG-mediated adhesion slows T cell migration; knockout removes 'brake' on migration.", "protein": "SELPLG (PSGL-1)", "relationship_type": "causal", "source_pmcid": "PMC12695837" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation of G protein is essential for proper folding and viral infectivity.", "mechanism": "Glycoprotein mediates viral entry into host neurons, causing infection.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "causal", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Encephalitis", "glycan_involvement": "Glycosylation supports neuroinvasiveness and immune evasion.", "mechanism": "G protein enables rabies virus to invade the central nervous system, leading to fatal encephalitis.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "causal", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Antibody glycosylation may affect stability and effector function, but not directly discussed.", "mechanism": "NC08 mAb binds rabies G protein, neutralizing virus and preventing infection.", "protein": "NC08 monoclonal antibody (scFv)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation sites may influence antigenicity and antibody binding.", "mechanism": "G protein is the main target for neutralizing antibodies and vaccine-induced immunity.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Mutations may indirectly affect glycan interactions or antibody stability.", "mechanism": "Affinity-matured NC08 mutants (e.g., S5A, K18F, N29C, S4I-P35S-N76D, S14H-T32N) show enhanced neutralization of rabies virus.", "protein": "NC08 monoclonal antibody (scFv)", "relationship_type": "protective", "source_pmcid": "PMC12695841" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Presence of G protein is used to detect rabies virus in diagnostic assays.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "biomarker", "source_pmcid": "PMC12695841" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation of VSV-G is necessary for pseudovirus infectivity.", "mechanism": "VSV-G used in pseudovirus systems to study rabies G protein-mediated entry.", "protein": "Vesicular stomatitis virus glycoprotein (VSV-G)", "relationship_type": "experimental model", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Potential impact on antibody glycosylation and manufacturability (e.g., N29C mutation may affect stability).", "mechanism": "Mutant NC08 antibodies with improved affinity can serve as next-generation rabies therapeutics.", "protein": "NC08 monoclonal antibody (scFv)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12695841" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycan shielding of epitopes.", "mechanism": "Glycosylation of G protein may help rabies virus evade host immune responses.", "protein": "Rabies virus glycoprotein (G protein)", "protein_enriched": { "function": "Attaches the virus to host cellular receptor, inducing endocytosis of the virion by using different host proteins including TFRC, GRM2 and ITGB1 (PubMed:30028877, PubMed:31666383, PubMed:36779762). In", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P08667" }, "relationship_type": "immune evasion", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Unpaired cysteine may affect glycan attachment or antibody folding.", "mechanism": "N29C mutation introduces unpaired cysteine, potentially leading to cysteinylation and reduced antibody stability/activity.", "protein": "NC08 monoclonal antibody (scFv)", "relationship_type": "manufacturing concern", "source_pmcid": "PMC12695841" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation of gB is essential for viral infectivity and immune evasion.", "mechanism": "gB mediates viral entry and cell fusion; mutations in gB enhance oncolytic HSV targeting of GBM cells.", "protein": "Herpes Simplex Virus glycoprotein B (gB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12696497" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation of gC modulates host immune recognition.", "mechanism": "gC facilitates viral attachment to host cells; used as a marker for viral infection in GBM therapy.", "protein": "Herpes Simplex Virus glycoprotein C (gC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "IL-12 is a glycoprotein; glycosylation is required for secretion and bioactivity.", "mechanism": "IL-12 expression by oHSV induces anti-tumor immunity, macrophage polarization, and T cell expansion.", "protein": "Interleukin-12 (IL-12)", "protein_enriched": { "function": "Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine (PubMed:8605935, PubMed:8943050). IL-12 is primarily produced by professional antigen-presenting cel", "gene_name": "IL12A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P29459" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Heavily glycosylated; glycosylation affects signaling and cell-cell interactions.", "mechanism": "CD45+ immune cell infiltration is used to assess immune response in GBM TME.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation modulates integrin function and cell adhesion.", "mechanism": "CD11b+ myeloid cells (macrophages/microglia) accumulate in GBM TME after oHSV:IL-12 therapy.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation affects receptor-ligand interactions.", "mechanism": "F4/80+ macrophages increase at tumor margins after oHSV:IL-12, indicating macrophage recruitment.", "protein": "F4/80 (EMR1)", "protein_enriched": { "function": "Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development", "gene_name": "Adgre1", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q61549" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may affect receptor stability and signaling.", "mechanism": "P2RY12+ microglia decrease after oHSV:IL-12, reflecting myeloid compartment shifts.", "protein": "P2RY12", "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation influences TCR signaling and stability.", "mechanism": "CD8a+ T cell infiltration and clonotype expansion are associated with anti-tumor immunity post oHSV:IL-12.", "protein": "CD8a", "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation modulates receptor function and immune synapse formation.", "mechanism": "CD4+ T cell numbers increase after oHSV:IL-12, indicating enhanced immune response.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation affects integrin-mediated adhesion.", "mechanism": "CD49b+ NK cell frequency changes reflect immune modulation in GBM TME after therapy.", "protein": "CD49b (ITGA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12696497" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "N-glycosylation required for secretion and anticoagulant function.", "mechanism": "Protein C deficiency increases risk of hepatic vein thrombosis.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "N-glycosylation affects plasma stability and activity.", "mechanism": "Protein S deficiency impairs anticoagulant pathway, promoting thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "N-glycosylation modulates inhibitory activity.", "mechanism": "Antithrombin deficiency leads to increased risk of hepatic vein thrombosis.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "Glycosylation influences protein stability and function.", "mechanism": "Factor V Leiden mutation causes resistance to activated protein C, increasing thrombosis risk.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "N-glycosylation required for secretion and clotting activity.", "mechanism": "Prothrombin G20210A mutation increases prothrombin levels, promoting thrombosis.", "protein": "Prothrombin (Factor II)", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation modulates antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I contribute to APS-related thrombosis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Myeloproliferative Neoplasms", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "JAK2 V617F mutation drives MPNs, increasing risk of hepatic vein thrombosis in BCS.", "protein": "JAK2", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "medium", "disease": "Myeloproliferative Neoplasms", "glycan_involvement": "Glycosylation affects chaperone function in ER.", "mechanism": "CALR mutations promote MPNs, predisposing to BCS.", "protein": "Calreticulin (CALR)", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "medium", "disease": "Myeloproliferative Neoplasms", "glycan_involvement": "N-glycosylation required for cell surface expression and signaling.", "mechanism": "MPL mutations drive ET/MPN, increasing BCS risk.", "protein": "MPL (Thrombopoietin receptor)", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Budd-Chiari Syndrome", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Antiphospholipid antibodies targeting beta-2 glycoprotein I promote hepatic vein thrombosis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12696600" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation modulates CD44 isoform function and cell adhesion.", "mechanism": "Splice variants of CD44 promote tumor metastasis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Altered glycosylation affects CD44-mediated cell migration.", "mechanism": "CD44 splice variants drive metastatic behavior.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Collagen glycosylation influences extracellular matrix remodeling.", "mechanism": "Differential isoform usage and polyadenylation in COL1A2 linked to fibroblast transition in metastases.", "protein": "COL1A2", "relationship_type": "biomarker", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation modulates collagen structure and tumor microenvironment.", "mechanism": "Isoform changes in COL3A1 associated with cancer-associated fibroblast formation.", "protein": "COL3A1", "relationship_type": "biomarker", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "MHC I glycosylation affects antigen presentation.", "mechanism": "AS-derived neoepitopes presented by MHC I are abundant and immunogenic.", "protein": "MHC I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation status may modulate TP53 stability and function.", "mechanism": "Missense mutations in TP53 dysregulate alternative splicing.", "protein": "TP53", "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "SRSF3 regulates splicing of glycoprotein-encoding genes.", "mechanism": "Downregulation of SRSF3 promotes metastatic HCC via altered splicing.", "protein": "SRSF3", "protein_enriched": { "function": "Could coordinate an aspect of bone turnover", "gene_name": "SPP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13103" }, "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "medium", "disease": "Myeloid malignancies", "glycan_involvement": "Splicing changes affect glycoprotein expression in hematopoietic cells.", "mechanism": "SRSF2 mutations disrupt splicing in myeloid cancers.", "protein": "SRSF2", "protein_enriched": { "function": "Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites", "gene_name": "SRSF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01130" }, "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "low", "disease": "Neurodevelopmental disorders", "glycan_involvement": "Glycosylation regulates EPHB1 receptor signaling.", "mechanism": "Splicing-associated variant alters upstream open reading frame, impacting translation.", "protein": "EPHB1", "protein_enriched": { "function": "Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The s", "gene_name": "EPHA1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P21709" }, "relationship_type": "causal", "source_pmcid": "PMC12696714" }, { "confidence": "high", "disease": "Chronic myelogenous leukemia", "glycan_involvement": "Glycosylation may affect fusion protein stability and immune recognition.", "mechanism": "Fusion transcript drives leukemogenesis; targeted by tyrosine kinase inhibitors.", "protein": "BCR/ABL1 fusion", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12696714" }, { "confidence": "high", "disease": "Hepatic tuberculosis", "glycan_involvement": "ALP is a glycoprotein; glycosylation is required for its stability and secretion.", "mechanism": "ALP is elevated in hepatic TB, especially in immunocompromised individuals, reflecting cholestatic liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696752" }, { "confidence": "medium", "disease": "Hepatic tuberculosis", "glycan_involvement": "GGT is glycosylated, which is important for its membrane localization and function.", "mechanism": "GGT is often elevated in hepatic TB, indicating biliary tract involvement.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696752" }, { "confidence": "high", "disease": "Hepatic tuberculosis", "glycan_involvement": "MPT64 is a secreted protein; glycosylation may affect antigenicity and detection.", "mechanism": "Detection of MPT64 antigen in culture confirms Mycobacterium tuberculosis complex infection.", "protein": "MPT64 antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12696752" }, { "confidence": "medium", "disease": "Liver abscess", "glycan_involvement": "Glycosylation is essential for ALP's enzymatic activity and serum stability.", "mechanism": "ALP is elevated in liver abscess, including tubercular etiology.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696752" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation status may influence ALP levels in immunocompromised states.", "mechanism": "ALP levels are higher in hepatic TB among HIV-infected individuals, reflecting greater liver involvement.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12696752" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation affects stability and function in circulation.", "mechanism": "Serum levels elevated in CKD and AKI; inhibits vascular calcification.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Highly glycosylated; glycosylation essential for secretion and function.", "mechanism": "Serum levels decrease with CKD progression; reflects tubular damage.", "protein": "Uromodulin", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation required for urinary excretion.", "mechanism": "Lower levels in AKI than CKD; indicates acute tubular injury.", "protein": "Uromodulin", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation modulates stability and receptor interactions.", "mechanism": "Serum levels elevated in CKD and AKI; mitigates inflammation and fibrosis.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation influences renal clearance.", "mechanism": "Serum levels increase with CKD severity; correlates with GFR decline.", "protein": "Beta-2 microglobulin (B2M)", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation affects filtration and catabolism.", "mechanism": "Serum levels increase with AKI severity; reflects decreased renal clearance.", "protein": "Beta-2 microglobulin (B2M)", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Early and sensitive marker; rises before creatinine in AKI.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation essential for function.", "mechanism": "Serum levels increase with CKD progression; correlates with severity.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation affects renal clearance and stability.", "mechanism": "Serum levels increase with CKD and AKI; alternative marker for GFR.", "protein": "Beta trace protein (BTP)", "relationship_type": "biomarker", "source_pmcid": "PMC12697015" }, { "confidence": "medium", "disease": "Vascular Calcification", "glycan_involvement": "Glycosylation modulates anti-calcification activity.", "mechanism": "Inhibits vascular calcification, which is linked to CKD mortality.", "protein": "Fetuin-A", "relationship_type": "protective", "source_pmcid": "PMC12697015" }, { "confidence": "high", "disease": "Impaired bone matrix/fracture toughness", "glycan_involvement": "Periostin is a glycoprotein; glycosylation may affect its stability and matrix interactions.", "mechanism": "Decreased abundance of Periostin in bone matrix is associated with reduced fracture toughness following gut microbiome alteration.", "protein": "Periostin", "relationship_type": "causal", "source_pmcid": "PMC12697349" }, { "confidence": "high", "disease": "Impaired bone matrix/fracture toughness", "glycan_involvement": "Emilin-1 is glycosylated; glycan structures may modulate its extracellular matrix function.", "mechanism": "Reduced Emilin-1 levels in bone matrix correlate with decreased fracture toughness in mice with altered gut microbiome.", "protein": "Emilin-1", "protein_enriched": { "function": "Involved in elastic and collagen fibers formation. It is required for EFEMP2 deposition into the extracellular matrix, and collagen network assembly and cross-linking via protein-lysine 6-oxidase/LOX ", "gene_name": "EMILIN1", "glycan_count": 60, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G57321FI", "G29068FM", "G44753VC", "G45395BF", "G73027HY", "G00912UN", "G02815KT", "G02886BB", "G04657PL", "G05049YU", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G23863VK", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G39446WN", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G46691LC", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G84225JN", "G84452RH", "G90382BL", "G90659AW", "G95177YH", "G37412TK", "G43769HG", "G48414YA", "G49955PK", "G50045TK", "G62765YT", "G76295SF", "G80920RR", "G83646BJ", "G85282JO", "G86182NS", "G95865ZB", "G98611JV", "G49108TO" ], "uniprot_id": "Q9Y6C2" }, "relationship_type": "causal", "source_pmcid": "PMC12697349" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Aberrant O-glycosylation of MUC1 exposes tumor-associated epitopes.", "mechanism": "MUC1 is overexpressed on the surface of CRC cells, enabling detection and targeting.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "N-glycosylation affects EPCAM stability and cell surface localization.", "mechanism": "EPCAM is upregulated on CRC cell surfaces, serving as a marker for tumor detection.", "protein": "Epithelial Cell Adhesion Molecule (EPCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Tumor-specific glycoforms of MUC1 are selectively recognized by antibodies.", "mechanism": "Targeting MUC1 with antibodies enables enhanced visualization and detection of CRC lesions.", "protein": "Mucin-1 (MUC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Glycosylation modulates EPCAM antigenicity and antibody binding.", "mechanism": "Antibody targeting of EPCAM improves detection sensitivity for heterogeneous CRC lesions.", "protein": "Epithelial Cell Adhesion Molecule (EPCAM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Altered O-glycosylation patterns in CRC enhance MUC1 detectability.", "mechanism": "Multiplexed detection of MUC1 increases sensitivity for identifying CRC lesions with variable expression.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "N-glycosylation influences EPCAM expression heterogeneity.", "mechanism": "Concurrent detection of EPCAM with MUC1 captures a broader range of CRC phenotypes.", "protein": "Epithelial Cell Adhesion Molecule (EPCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Tumor-associated O-glycans on MUC1 facilitate antibody recognition.", "mechanism": "Surface MUC1 expression correlates with tumor presence in orthotopic CRC models.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Glycosylation state affects EPCAM surface presentation.", "mechanism": "EPCAM-positive tumoroids are reliably detected in heterogeneous CRC models.", "protein": "Epithelial Cell Adhesion Molecule (EPCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "O-glycosylation of MUC1 is critical for antibody binding and detection.", "mechanism": "APL-MPs targeting MUC1 enable detection of CRC antigens on the luminal colon surface in vivo.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "N-glycosylation modulates EPCAM accessibility for antibody-based detection.", "mechanism": "APL-MPs targeting EPCAM enhance sensitivity for CRC lesion detection in complex tissue environments.", "protein": "Epithelial Cell Adhesion Molecule (EPCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12697353" }, { "confidence": "high", "disease": "Motor Neuropathy", "glycan_involvement": "Not directly discussed; LDHB is predicted to be glycosylated, which may affect stability or localization.", "mechanism": "Loss of LDHB impairs lactate metabolism in motor neurons, leading to early motor neuropathy.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "causal", "source_pmcid": "PMC12697354" }, { "confidence": "high", "disease": "Neuromuscular Junction Atrophy", "glycan_involvement": "Not directly discussed; glycosylation may modulate LDHB function.", "mechanism": "LDHB knockout leads to progressive neuromuscular junction atrophy without axon degeneration.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "causal", "source_pmcid": "PMC12697354" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed; glycosylation could influence LDHB activity in disease context.", "mechanism": "Rare loss-of-function LDHB variants found in ALS patients; LDHB deficiency synergizes with ALS genetic risk factors to accelerate motor decline.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "modifier/causal", "source_pmcid": "PMC12697354" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not discussed; TDP-43 glycosylation status may affect aggregation or function.", "mechanism": "TDP43-Q331K knock-in allele is a mild ALS risk variant; synergizes with LDHB deficiency to produce early motor neuropathy.", "protein": "TDP-43", "relationship_type": "causal", "source_pmcid": "PMC12697354" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not discussed; SOD1 glycosylation may affect folding or aggregation.", "mechanism": "Sod1-D83G knock-in allele is a mild ALS risk variant; synergizes with LDHB deficiency to accelerate motor decline.", "protein": "SOD1", "relationship_type": "causal", "source_pmcid": "PMC12697354" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not discussed; glycosylation could affect LDHB as a drug target.", "mechanism": "Lactate metabolism (via LDHB) is identified as a therapeutic target for modifying motor system vulnerability in ALS.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12697354" }, { "confidence": "medium", "disease": "Motor Neuropathy", "glycan_involvement": "Not discussed.", "mechanism": "LDHB deficiency is associated with early motor neuropathy, suggesting its potential as a biomarker.", "protein": "LDHB", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07195" }, "relationship_type": "biomarker", "source_pmcid": "PMC12697354" }, { "confidence": "high", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "IL-1\u03b2 downregulates OAT1 mRNA and activity via JNK signaling, reducing renal drug clearance.", "protein": "OAT1 (SLC22A6)", "protein_enriched": { "function": "Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one mol", "gene_name": "SLC22A6", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q4U2R8" }, "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "high", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation supports transporter stability.", "mechanism": "IL-1\u03b2 downregulates OAT2 mRNA via p38 MAPK, impairing renal secretion.", "protein": "OAT2 (SLC22A7)", "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "high", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation essential for transporter function.", "mechanism": "IL-1\u03b2 downregulates OAT3 mRNA and activity via JNK signaling.", "protein": "OAT3 (SLC22A8)", "protein_enriched": { "function": "Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP", "gene_name": "CYTH4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UIA0" }, "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation affects substrate specificity.", "mechanism": "IL-1\u03b2 downregulates OAT4 mRNA, mechanism MAPK/NF-\u03baB-independent.", "protein": "OAT4 (SLC22A11)", "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation required for transporter activity.", "mechanism": "IL-1\u03b2 downregulates OCT2 mRNA, mechanism MAPK/NF-\u03baB-independent.", "protein": "OCT2 (SLC22A2)", "protein_enriched": { "function": "Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:96875", "gene_name": "SLC22A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O15244" }, "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation modulates transporter efficiency.", "mechanism": "IL-1\u03b2 upregulates OCTN1 mRNA via NF-\u03baB, potentially compensating for reduced organic anion transport.", "protein": "OCTN1 (SLC22A4)", "protein_enriched": { "function": "Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:2220662", "gene_name": "SLC22A4", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H015" }, "relationship_type": "protective", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation influences membrane trafficking.", "mechanism": "IL-1\u03b2 downregulates MATE2-K mRNA, reducing drug efflux.", "protein": "MATE2-K (SLC47A2)", "protein_enriched": { "function": "Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium", "gene_name": "SLC47A2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86VL8" }, "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "N-glycosylation critical for transporter stability.", "mechanism": "IL-1\u03b2 downregulates MRP2 mRNA, impairing drug excretion.", "protein": "MRP2 (ABCC2)", "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "IL-1\u03b2 upregulates MRP3 mRNA, may enhance alternative drug clearance.", "protein": "MRP3 (ABCC3)", "relationship_type": "protective", "source_pmcid": "PMC12697364" }, { "confidence": "medium", "disease": "Inflammatory kidney disease", "glycan_involvement": "Glycosylation affects substrate binding.", "mechanism": "IL-1\u03b2 downregulates OATP4C1 mRNA, reducing uptake of endogenous and exogenous compounds.", "protein": "OATP4C1 (SLCO4C1)", "protein_enriched": { "function": "Required to promote assembly of the transition zone in primary cilia. Acts by specifically recognizing and binding the axonemal microtubule. Localizes to the distal ends of centrioles before ciliogene", "gene_name": "Cep162", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6ZQ06" }, "relationship_type": "causal", "source_pmcid": "PMC12697364" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Env is heavily glycosylated, forming a glycan shield that protects the virus from neutralizing antibodies.", "mechanism": "Env mediates viral entry into host cells via CD4 and coreceptor binding.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC12697668" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycan-dependent epitopes (e.g., V2-apex, V3-glycan) are targeted by bnAbs.", "mechanism": "Env is the primary target for broadly neutralizing antibodies (bnAbs) induced by vaccines.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12697668" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation patterns influence neutralization sensitivity and antibody recognition.", "mechanism": "Neutralization sensitivity of Env pseudoviruses is used to assess vaccine-elicited antibody responses.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC12697668" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycan sites (e.g., V3-glycan, V2-apex) are critical for bnAb binding and neutralization.", "mechanism": "Induction of bnAbs against glycan-dependent Env epitopes can confer protection.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "protective", "source_pmcid": "PMC12697668" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycan heterogeneity among Envs affects breadth and potency of antibody responses.", "mechanism": "Env is used in pseudovirus panels to screen for bnAb activity in vaccine studies.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12697668" }, { "confidence": "high", "disease": "Lumpy Skin Disease (LSD)", "glycan_involvement": "Glycosylation of EEV glycoprotein is critical for viral envelope integrity and infectivity.", "mechanism": "EEV glycoprotein is involved in viral entry and spread; a 27-nucleotide insertion distinguishes field strains and may affect virulence.", "protein": "EEV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12697798" }, { "confidence": "high", "disease": "Lumpy Skin Disease (LSD)", "glycan_involvement": "Glycosylation may affect receptor function and immune evasion.", "mechanism": "GPCR gene sequence (12-nt deletion) is used to differentiate field strains from vaccine/recombinant strains.", "protein": "GPCR", "relationship_type": "biomarker", "source_pmcid": "PMC12697798" }, { "confidence": "medium", "disease": "Lumpy Skin Disease (LSD)", "glycan_involvement": "Glycosylation status may influence immunogenicity.", "mechanism": "B22R gene sequence distinguishes field isolates from vaccine strains due to specific nucleotide insertions.", "protein": "B22R protein", "relationship_type": "biomarker", "source_pmcid": "PMC12697798" }, { "confidence": "medium", "disease": "Lumpy Skin Disease (LSD)", "glycan_involvement": "Potential glycosylation could affect protein stability and immune modulation.", "mechanism": "Truncation of LD087 may impair host immune response, contributing to increased virulence and higher case fatality rates in yaks.", "protein": "MutT motif protein (LD087)", "relationship_type": "causal", "source_pmcid": "PMC12697798" }, { "confidence": "low", "disease": "Lumpy Skin Disease (LSD)", "glycan_involvement": "Kelch-like proteins often have glycosylation sites impacting function.", "mechanism": "Frameshift mutations in LD019b may alter viral protein interactions, possibly affecting pathogenesis.", "protein": "Kelch-like protein (LD019b)", "relationship_type": "causal", "source_pmcid": "PMC12697798" }, { "confidence": "medium", "disease": "Abortion in yaks", "glycan_involvement": "Glycosylation may enhance tissue tropism.", "mechanism": "EEV glycoprotein-mediated viral spread leads to severe systemic infection, resulting in abortion.", "protein": "EEV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12697798" }, { "confidence": "low", "disease": "Shipping fever", "glycan_involvement": "Glycosylation may modulate host-pathogen interactions.", "mechanism": "EEV glycoprotein may facilitate co-infection with Mannheimia species, exacerbating disease severity.", "protein": "EEV glycoprotein", "relationship_type": "co-infection facilitator", "source_pmcid": "PMC12697798" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation of vWF regulates its function and interaction with platelets.", "mechanism": "Exposure of vWF after endothelial injury promotes platelet adhesion and thrombus formation at device sites.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycans modulate fibrinogen's interaction with integrins.", "mechanism": "Adsorbed fibrinogen on device surfaces mediates platelet adhesion and aggregation, initiating clot formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Fibrotic encapsulation", "glycan_involvement": "Glycosylation affects fibronectin's cell-binding properties.", "mechanism": "Fibronectin deposition on device surfaces supports fibroblast migration and ECM formation, leading to fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "high", "disease": "Inflammation (Foreign Body Response)", "glycan_involvement": "Glycosylation is essential for C3 function and activation.", "mechanism": "Device surface adsorption activates complement C3, generating C3a which recruits immune cells and amplifies inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Inflammation (Foreign Body Response)", "glycan_involvement": "Sialylated O-glycans are critical for ligand recognition.", "mechanism": "Mediates leukocyte adhesion to activated platelets on device surfaces, promoting inflammation.", "protein": "P-selectin glycoprotein ligand-1", "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation required for anticoagulant activity.", "mechanism": "Endothelial thrombomodulin inhibits coagulation; loss after device-induced injury shifts balance to thrombosis.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12697825" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Composed of glycoproteins and proteoglycans; glycan loss impairs function.", "mechanism": "Glycocalyx inhibits platelet adhesion and regulates coagulation; device-induced damage increases thrombosis risk.", "protein": "Endothelial glycocalyx (ensemble)", "relationship_type": "protective", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Inflammation (Foreign Body Response)", "glycan_involvement": "Glycosylation required for C5 cleavage and function.", "mechanism": "C5a generated at device surface acts as a chemoattractant, amplifying immune cell recruitment and inflammation.", "protein": "Complement C5", "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates TF activity.", "mechanism": "Upregulated on endothelium/monocytes after device implantation, initiating extrinsic coagulation.", "protein": "Tissue factor", "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "medium", "disease": "Restenosis", "glycan_involvement": "Glycosylation affects cell-ECM interactions.", "mechanism": "Fibronectin supports VSMC migration and ECM deposition, contributing to neointimal thickening and restenosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12697825" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation of cell cycle and transcriptional regulators", "mechanism": "Elevated OGT and O-GlcNAc promote tumor cell proliferation, invasion, and are increased in high-grade cancers.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6769692" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "O-GlcNAc modification of insulin signaling proteins", "mechanism": "Hyperglycemia increases O-GlcNAcylation, contributing to insulin resistance.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation increases Cyclin D1 expression/activity", "mechanism": "O-GlcNAc modification upregulates Cyclin D1, promoting G1/S transition and proliferation.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation modulates \u03b2-catenin function", "mechanism": "O-GlcNAc modification regulates \u03b2-catenin nuclear localization and activity, affecting proliferation.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "high", "disease": "Embryonic lethality", "glycan_involvement": "O-GlcNAc modification of cell cycle proteins", "mechanism": "OGT deletion is fatal; O-GlcNAc is essential for embryonic stem cell viability.", "protein": "O-GlcNAc Transferase (OGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "high", "disease": "Embryonic lethality", "glycan_involvement": "O-GlcNAc removal from regulatory proteins", "mechanism": "OGA deletion is fatal; proper O-GlcNAc cycling is required for development.", "protein": "O-GlcNAcase (OGA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "medium", "disease": "Beta cell dysfunction", "glycan_involvement": "O-GlcNAcylation of NeuroD1", "mechanism": "O-GlcNAc modification regulates NeuroD1 nuclear transport, affecting insulin gene transcription.", "protein": "NeuroD1", "protein_enriched": { "function": "Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coact", "gene_name": "NEUROD1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13562" }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "medium", "disease": "Beta cell dysfunction", "glycan_involvement": "O-GlcNAcylation of Pdx-1", "mechanism": "O-GlcNAc modification of Pdx-1 modulates insulin production and beta cell maturation.", "protein": "Pdx-1", "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation modulates PLK1 levels", "mechanism": "O-GlcNAc modification regulates PLK1 expression; PLK1 overexpression promotes cancer.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6769692" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "O-GlcNAcylation of Aurora B and associated spindle proteins", "mechanism": "O-GlcNAc modification affects Aurora B function, impacting mitosis and chromosome segregation.", "protein": "Aurora B kinase", "protein_enriched": { "function": "Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722", "gene_name": "AURKB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59924QI", "G49108TO" ], "uniprot_id": "Q96GD4" }, "relationship_type": "causal", "source_pmcid": "PMC6769692" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "O-glycosylation via hexosamine pathway impairs function.", "mechanism": "O-GlcNAcylation of IRS-1 reduces insulin signaling, promoting insulin resistance.", "protein": "IRS-1", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "O-glycosylation via hexosamine pathway.", "mechanism": "O-GlcNAcylation of IRS-2 impairs insulin signaling, contributing to T2DM development.", "protein": "IRS-2", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "high", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "Glycosylation status affects trafficking and function.", "mechanism": "Downregulation of GLUT4 in adipose tissue during pregnancy and GDM reduces glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "biomarker", "source_pmcid": "PMC7598660" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Decreased adiponectin secretion in pregnancy and GDM reduces insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC7598660" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "Epigenetic changes in LEP gene methylation after GDM exposure linked to obesity risk.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC7598660" }, { "confidence": "high", "disease": "Diabetic retinopathy", "glycan_involvement": "Non-enzymatic glycation of proteins.", "mechanism": "AGEs increase ROS via PKC-NOX2 activation, contributing to microvascular complications.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "O-glycosylation of histones and transcription factors.", "mechanism": "OGT-mediated O-GlcNAcylation alters epigenetic marks, affecting metabolic gene expression.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "O-glycosylation via OGT.", "mechanism": "O-GlcNAcylation of HCF1 regulates histone methylation, influencing metabolic gene expression.", "protein": "HCF1", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "medium", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Higher GST activity in females provides protection against oxidative stress in GDM.", "protein": "GST", "relationship_type": "protective", "source_pmcid": "PMC7598660" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Indirect; glycosylation status may affect stability.", "mechanism": "Oxidative stress reduces PDX-1 activity, impairing insulin biosynthesis and secretion.", "protein": "PDX-1", "relationship_type": "causal", "source_pmcid": "PMC7598660" }, { "confidence": "high", "disease": "Implantation failure", "glycan_involvement": "O-GlcNAc modification of nuclear and cytoplasmic proteins alters trophoblast differentiation.", "mechanism": "Elevated O-GlcNAcylation (e.g., in diabetes) is associated with reduced implantation rates.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "high", "disease": "Placental dysfunction", "glycan_involvement": "O-GlcNAcylation affects differentiation and function of trophoblast populations.", "mechanism": "Increased O-GlcNAcylation impairs placental vascularisation and function.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Adverse neonatal outcomes", "glycan_involvement": "O-GlcNAcylation mediates stress adaptation in trophoblasts.", "mechanism": "Stress-induced O-GlcNAcylation during early gestation leads to altered offspring growth and behavior.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "high", "disease": "Diabetes-associated implantation defects", "glycan_involvement": "O-GlcNAcylation integrates metabolic signals affecting implantation.", "mechanism": "Maternal diabetes increases O-GlcNAcylation in blastocysts and endometrium, reducing implantation.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Obesity-associated placental phenotypes", "glycan_involvement": "O-GlcNAcylation links nutrient status to placental cell fate.", "mechanism": "Obesity elevates O-GlcNAcylation, altering placental development.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Hypertension-associated placental phenotypes", "glycan_involvement": "O-GlcNAcylation mediates stress responses in trophoblasts.", "mechanism": "Hypertension is associated with increased O-GlcNAcylation and placental changes.", "protein": "O-GlcNAcylated proteins", "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Implantation failure", "glycan_involvement": "O-GlcNAcylation upregulates fusogenic glycoprotein expression.", "mechanism": "Upregulation of ERVFRD1 by O-GlcNAcylation promotes syncytiotrophoblast differentiation and invasion.", "protein": "ERVFRD1 (syncytin-2)", "protein_enriched": { "function": "May play a role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which", "gene_name": "PIWIL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q7Z3Z3" }, "relationship_type": "protective", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Implantation failure", "glycan_involvement": "O-GlcNAcylation regulates transcription factor activity.", "mechanism": "O-GlcNAcylation increases GCM1 expression, promoting trophoblast differentiation.", "protein": "GCM1", "protein_enriched": { "function": "Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes (PubMed:10542267, PubMed:18160678). Binds to the trophoblast-specific elem", "gene_name": "GCM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP62" }, "relationship_type": "protective", "source_pmcid": "PMC7599815" }, { "confidence": "medium", "disease": "Placental dysfunction", "glycan_involvement": "OGT mediates O-GlcNAc addition to target proteins.", "mechanism": "Altered OGT expression affects O-GlcNAcylation balance, impacting placental development.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "high", "disease": "Placental dysfunction", "glycan_involvement": "OGA removes O-GlcNAc from proteins, regulating modification levels.", "mechanism": "OGA deletion increases O-GlcNAcylation, impairing placental vascularisation.", "protein": "O-GlcNAcase (OGA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7599815" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "Elevated circulating apoA-I enhances cholesterol efflux and reduces atherosclerotic plaque burden.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "protective", "source_pmcid": "PMC7617243" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "Administration or upregulation of apoA-I lowers atherosclerosis burden in patients.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "protective", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "UBE4A is not a glycoprotein; no glycan involvement.", "mechanism": "UBE4A induces p53 degradation, promoting cancer cell proliferation.", "protein": "UBE4A", "relationship_type": "causal", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "UBE4A is not a glycoprotein; no glycan involvement.", "mechanism": "UBE4A deletion causes insulin resistance and hepatic steatosis.", "protein": "UBE4A", "relationship_type": "causal", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Neuronal developmental defects", "glycan_involvement": "UBE4A is not a glycoprotein; no glycan involvement.", "mechanism": "UBE4A deletion causes severe neuronal developmental defects in animal models.", "protein": "UBE4A", "relationship_type": "causal", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "Reduced plasma apoA-I and HDL are associated with nonalcoholic fatty liver disease.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "biomarker", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "IP6K1 is a therapeutic target for diabetes; its inhibition increases apoA-I.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "biomarker", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "IP6K1 levels are increased in obesity, associated with reduced apoA-I and HDL.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "biomarker", "source_pmcid": "PMC7617243" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ABCA1 is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "ABCA1 is essential for nascent HDL biogenesis; interacts with apoA-I for cholesterol efflux.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC7617243" }, { "confidence": "low", "disease": "Ischemia-reperfusion injury", "glycan_involvement": "ApoA-I is a glycoprotein; glycosylation not directly implicated in mechanism here.", "mechanism": "Blocking IP6K1 protects the heart against ischemia-reperfusion injury, possibly via increased apoA-I.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "protective", "source_pmcid": "PMC7617243" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "No direct glycosylation; methylation status affects gene expression.", "mechanism": "Mutations in DNMT3A drive clonal haematopoiesis, increasing CVD risk via altered DNA methylation.", "protein": "DNMT3A", "protein_enriched": { "function": "Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation ", "gene_name": "DNMT3A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K1" }, "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "O-GlcNAcylation of TET2 modulates its activity; altered in diabetes/oxidative stress.", "mechanism": "TET2 mutations promote clonal haematopoiesis and CVD by altering DNA demethylation and gene regulation.", "protein": "TET2", "protein_enriched": { "function": "Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for", "gene_name": "TET2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6N021" }, "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "O-GlcNAcylation of TET2 increased in diabetes, affecting function.", "mechanism": "Decreased TET2 activity and 5-hmC levels in PBMCs of diabetics; linked to hyperglycaemia and redox changes.", "protein": "TET2", "protein_enriched": { "function": "Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for", "gene_name": "TET2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6N021" }, "relationship_type": "biomarker", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Directly adds O-GlcNAc to TETs; dysregulated in CVD risk states.", "mechanism": "OGT modifies TET proteins via O-GlcNAcylation, impacting DNA methylation and endothelial function.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "eNOS is N-glycosylated, which may affect stability and localization.", "mechanism": "Aberrant methylation of eNOS gene reduces expression, decreasing NO and promoting dysfunction.", "protein": "eNOS (NOS3)", "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates adhesive function.", "mechanism": "Altered methylation and expression affect endothelial barrier and leukocyte trafficking.", "protein": "VE-cadherin (CDH5)", "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Heavily glycosylated; glycan structures mediate leukocyte binding.", "mechanism": "Selectin expression and function (glycoprotein-mediated adhesion) are altered in endothelial dysfunction.", "protein": "Selectins", "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Smoking-related cancers", "glycan_involvement": "O-GlcNAcylation may modulate TET2 in response to oxidative stress from smoking.", "mechanism": "Altered 5-hmC levels in lung cells and blood associate with smoking and cancer risk.", "protein": "TET2", "protein_enriched": { "function": "Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for", "gene_name": "TET2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6N021" }, "relationship_type": "biomarker", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Hyperhomocysteinemia", "glycan_involvement": "No direct glycosylation; effect is via methylation.", "mechanism": "Elevated SAH inhibits DNMT1, leading to hypomethylation and vascular dysfunction.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "causal", "source_pmcid": "PMC7617538" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "O-GlcNAcylation of TET2 may affect biomarker levels.", "mechanism": "5-hmC signatures in cell-free DNA are predictive for coronary artery disease.", "protein": "TET2", "protein_enriched": { "function": "Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for", "gene_name": "TET2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6N021" }, "relationship_type": "biomarker", "source_pmcid": "PMC7617538" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Loss of O-GlcNAcylation at Ser/Thr residues increases phosphorylation and aggregation.", "mechanism": "Reduced O-GlcNAcylation leads to tau hyperphosphorylation and toxicity, promoting AD pathology.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-GlcNAcylation regulates APP maturation and trafficking.", "mechanism": "Reduced O-GlcNAcylation favors amyloidogenic processing and A\u03b2 deposition.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-GlcNAcylation of NDUFB8 is required for optimal mitochondrial respiration.", "mechanism": "Reduced O-GlcNAcylation impairs Complex I activity, leading to mitochondrial dysfunction.", "protein": "NDUFB8", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "OGT is the key enzyme for O-GlcNAc addition.", "mechanism": "Altered OGT posttranslational modifications reduce its activity, decreasing global O-GlcNAcylation.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GFAT1 controls substrate supply for O-GlcNAcylation.", "mechanism": "AMPK-mediated inhibition of GFAT1 reduces HBP flux and UDP-GlcNAc synthesis, lowering O-GlcNAcylation.", "protein": "GFAT1", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "O-GlcNAcylation at inhibitory serine residues modulates IRS-1 function.", "mechanism": "Reduced O-GlcNAcylation increases inhibitory phosphorylation, disrupting insulin signaling.", "protein": "IRS-1", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "O-GlcNAcylation acts as a nutrient sensor in neurons.", "mechanism": "Reduced global O-GlcNAcylation in hippocampus correlates with impaired cognition.", "protein": "O-GlcNAcylated proteins (global)", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "O-GlcNAcylation of mitochondrial proteins is essential for bioenergetics.", "mechanism": "Reduced O-GlcNAcylation impairs mitochondrial function, contributing to neuronal energy failure.", "protein": "NDUFB8", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Hyper-O-GlcNAcylation in peripheral tissues promotes metabolic dysfunction.", "mechanism": "Increased O-GlcNAcylation in liver is associated with insulin resistance and glucose toxicity.", "protein": "O-GlcNAcylated proteins (liver)", "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "AMPK is both modified by and regulates O-GlcNAcylation.", "mechanism": "Hyperactivation of AMPK inhibits GFAT1, reducing O-GlcNAcylation and promoting AD-like changes.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8038495" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "O-GlcNAcylation of neuronal and intestinal proteins modulates immune response.", "mechanism": "O-GlcNAc cycling regulates stress response and defense gene expression; mutants are hypersusceptible to S. aureus.", "protein": "OGT-1/OGA-1", "relationship_type": "causal", "source_pmcid": "PMC8344176" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "O-GlcNAc modification of metabolic regulators.", "mechanism": "Aberrant O-GlcNAcylation linked to metabolic disease.", "protein": "OGT-1/OGA-1", "relationship_type": "causal", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "GPCR glycosylation may affect receptor function (not directly shown).", "mechanism": "NPR-1 regulates survival by modulating innate immunity and pathogen avoidance via p38/PMK-1 MAPK pathway.", "protein": "NPR-1", "protein_enriched": { "function": "", "gene_name": "nep-23", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T1" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Collagen glycosylation contributes to cuticle integrity.", "mechanism": "Loss of NPR-8 increases collagen gene expression, reinforcing cuticle and resistance to infection.", "protein": "NPR-8", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2S9" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "GPCR glycosylation may modulate receptor signaling (not directly shown).", "mechanism": "OCTR-1 suppresses immune response via insulin-like, p38/PMK-1 MAPK, and CED-1 pathways; loss enhances resistance.", "protein": "OCTR-1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T2" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "medium", "disease": "Serratia marcescens infection", "glycan_involvement": "Toll-like receptors are typically glycosylated, affecting ligand recognition.", "mechanism": "TOL-1 in BAG neurons required for avoidance behavior to S. marcescens.", "protein": "TOL-1", "protein_enriched": { "function": "", "gene_name": "nccd-1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T3" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "Insulin/IGF-1 receptors are N-glycosylated, impacting signaling.", "mechanism": "DAF-2 signaling in neurons regulates aversive learning and immune response.", "protein": "DAF-2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T4" }, "relationship_type": "causal", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "TGF-\u03b2 ligands are glycosylated, affecting secretion and activity.", "mechanism": "DAF-7/TGF-\u03b2 signaling in ASI/ASJ neurons mediates avoidance and transgenerational learning.", "protein": "DAF-7", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T5" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Transcription factors may be O-GlcNAcylated, modulating activity.", "mechanism": "ACh signaling activates LIN-1 to induce Wnt/Frizzle and immune genes, increasing survival.", "protein": "LIN-1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9U2T6" }, "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Collagen glycosylation critical for cuticle structure and pathogen resistance.", "mechanism": "Upregulation of collagen genes strengthens cuticle barrier against infection.", "protein": "Collagen (multiple genes)", "relationship_type": "protective", "source_pmcid": "PMC8344176" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for receptor function and trafficking.", "mechanism": "Reduced tyrosine kinase activity impairs insulin signaling in muscle and liver.", "protein": "IRTK", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "O-GlcNAcylation competes with phosphorylation, modulating activity.", "mechanism": "Reduced tyrosine phosphorylation and increased serine phosphorylation block downstream signaling.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation affects trafficking and membrane localization.", "mechanism": "Impaired translocation reduces glucose uptake in muscle and adipose tissue.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "O-glycosylation (O-GlcNAc) of IRS1/2, PI3K, Akt, and FOXO1.", "mechanism": "O-GlcNAcylation of insulin signaling proteins impairs their function.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "O-glycosylation removal from signaling proteins.", "mechanism": "Removes O-GlcNAc, improving insulin sensitivity and glucose tolerance.", "protein": "OGA/MGEA5", "relationship_type": "protective", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "O-glycosylation modulates secretion and function.", "mechanism": "Overexpression increases hepatic DAG and PKC\u03b5, promoting steatosis and insulin resistance.", "protein": "ApoC3", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for enzyme activity.", "mechanism": "Overexpression in liver/muscle increases lipid accumulation and impairs insulin signaling.", "protein": "LPL", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation affects membrane localization.", "mechanism": "Facilitates fatty acid uptake, promoting ectopic lipid accumulation and insulin resistance.", "protein": "FATP1", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation may affect enzyme stability.", "mechanism": "Knockout reduces hepatic ceramide, protecting against obesity and improving glucose tolerance.", "protein": "CerS6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Lipodystrophy", "glycan_involvement": "O-glycosylation modulates secretion.", "mechanism": "Inhibits adipocyte differentiation, leading to ectopic fat deposition and insulin resistance.", "protein": "Pref-1", "relationship_type": "causal", "source_pmcid": "PMC8831809" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "O-GlcNAc modification of proteins is altered.", "mechanism": "Reduced OGT/GnTIII in gut microbiota leads to aberrant O-GlcNAcylation, impacting glycemic control and kidney damage.", "protein": "O-GlcNAc transferase (OGT/GnTIII)", "relationship_type": "causal", "source_pmcid": "PMC8911313" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "LPS is a bacterial glycan that activates immune pathways.", "mechanism": "Increased LPS biosynthesis by Proteobacteria induces chronic inflammation via TLR activation, promoting DKD.", "protein": "Lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC8911313" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "TLRs recognize glycan structures on LPS.", "mechanism": "LPS binds TLRs, triggering inflammatory cascades implicated in DKD pathogenesis.", "protein": "Toll-like receptors (TLRs)", "relationship_type": "causal", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "GPCRs are glycoproteins; SCFA signaling modulates glycosylation indirectly.", "mechanism": "SCFAs activate GPCRs, reducing inflammation and protecting against DKD.", "protein": "G protein-coupled receptors (GPCRs)", "relationship_type": "protective", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "SCFA production is linked to carbohydrate metabolism and glycan degradation.", "mechanism": "SCFA-producing bacteria are reduced in DKD, leading to decreased anti-inflammatory effects.", "protein": "Short-chain fatty acids (SCFA)-related enzymes", "relationship_type": "protective", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Changes in heparan sulfate, chondroitin sulfate, dermatan sulfate biosynthesis.", "mechanism": "Altered glycosaminoglycan biosynthesis pathways in gut microbiota of DKD patients.", "protein": "Glycosaminoglycan biosynthesis enzymes", "relationship_type": "biomarker", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "LPS glycan structure triggers inflammation.", "mechanism": "Increased E. coli abundance correlates with DKD and higher urinary albumin creatinine ratio.", "protein": "Escherichia coli LPS", "relationship_type": "biomarker", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "LPS glycan structure involved in immune activation.", "mechanism": "Higher Citrobacter farmeri abundance is positively correlated with DKD severity (ACR).", "protein": "Citrobacter farmeri LPS", "relationship_type": "biomarker", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "LPS glycan structure involved in immune activation.", "mechanism": "Higher Syntrophaceticus schinkii abundance correlates with increased ACR in DKD.", "protein": "Syntrophaceticus schinkii LPS", "relationship_type": "biomarker", "source_pmcid": "PMC8911313" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Bacterial glycoproteins may modulate host immunity.", "mechanism": "Higher abundance in non-DKD group; negatively correlated with ACR, suggesting protective effect.", "protein": "Enterococcus caccae glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC8911313" }, { "confidence": "high", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "O-GlcNAcylation of target proteins by OGT increases inflammation.", "mechanism": "OGT promotes inflammatory signaling and severity of AP via O-GlcNAcylation of NF-\u03baB pathway proteins.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC8945657" }, { "confidence": "high", "disease": "Cerulein-induced pancreatitis", "glycan_involvement": "Lower O-GlcNAcylation reduces inflammatory response.", "mechanism": "Reduction of OGT in pancreas attenuates severity of cerulein-induced pancreatitis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Direct O-GlcNAcylation of NF-\u03baB p65 increases inflammatory signaling.", "mechanism": "O-GlcNAcylation of NF-\u03baB p65 by OGT enhances its activation and pro-inflammatory gene transcription.", "protein": "NF-\u03baB p65 (RelA)", "relationship_type": "causal", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "O-GlcNAcylation may regulate I\u03baB\u03b1 stability.", "mechanism": "OGT promotes I\u03baB\u03b1 degradation, facilitating NF-\u03baB activation.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "causal", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "O-GlcNAcylation modulates kinase activity.", "mechanism": "O-GlcNAcylation of IKK\u03b1 by OGT activates NF-\u03baB pathway.", "protein": "IKK\u03b1", "relationship_type": "causal", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Indirectly regulated by O-GlcNAcylation via NF-\u03baB pathway.", "mechanism": "Ccl2 mRNA is elevated in OGT-deficient mice with cerulein-induced pancreatitis.", "protein": "Ccl2 (MCP-1)", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ion", "gene_name": "Ccl2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P10148" }, "relationship_type": "biomarker", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Regulated by O-GlcNAcylation of NF-\u03baB pathway.", "mechanism": "Serum TNF-\u03b1 increases with cerulein-induced pancreatitis in controls but not in OGT-deficient mice.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8945657" }, { "confidence": "medium", "disease": "Metabolic dysfunction", "glycan_involvement": "O-GlcNAcylation modulates immune cell activation.", "mechanism": "OGT ablation suppresses macrophage proinflammatory activation and prevents diet-induced metabolic dysfunction.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC8945657" }, { "confidence": "high", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Lower O-GlcNAcylation dampens inflammatory response.", "mechanism": "Reduced OGT (and O-GlcNAcylation) protects against severe AP by decreasing macrophage infiltration and inflammatory markers.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine 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"high", "disease": "Intellectual disability", "glycan_involvement": "Abnormal glycosylation of neural proteins.", "mechanism": "Impaired N-glycosylation disrupts neuronal development and function.", "protein": "GMPPA (mannose-1-phosphate guanyltransferase alpha)", "protein_enriched": { "function": "Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubM", "gene_name": "NARS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96I59" }, "relationship_type": "causal", "source_pmcid": "PMC9283290" }, { "confidence": "medium", "disease": "Hypotonia", "glycan_involvement": "Impaired glycosylation of muscle/neuronal proteins.", "mechanism": "GMPPA-CDG leads to neuromuscular dysfunction due to glycosylation defects.", "protein": "GMPPA (mannose-1-phosphate guanyltransferase alpha)", "protein_enriched": { "function": "Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubM", "gene_name": "NARS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96I59" }, "relationship_type": "causal", "source_pmcid": "PMC9283290" }, { "confidence": "medium", "disease": "Short stature", "glycan_involvement": "Disrupted glycosylation of growth-related proteins.", "mechanism": "Growth impairment due to systemic effects of glycosylation defects.", "protein": "GMPPA (mannose-1-phosphate guanyltransferase alpha)", "protein_enriched": { "function": "Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubM", "gene_name": "NARS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96I59" }, "relationship_type": "causal", "source_pmcid": "PMC9283290" }, { "confidence": "medium", "disease": "GMPPA-congenital disorder of glycosylation (GMPPA-CDG)", "glycan_involvement": "Altered GDP-mannose synthesis impacts N-glycosylation.", "mechanism": "GMPPA regulates GMPPB; mutations in GMPPA affect GMPPB function and glycosylation.", "protein": "GMPPB (GDP-mannose pyrophosphorylase B)", "protein_enriched": { "function": "", "gene_name": "NARS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96I59-2" }, "relationship_type": "modifier", "source_pmcid": "PMC9283290" }, { "confidence": "high", "disease": "Epilepsy (childhood)", "glycan_involvement": "Lower core fucosylation and galactosylation; higher agalactosylation.", "mechanism": "Altered IgG glycosylation profile (decreased core fucosylation and galactosylation) associated with increased inflammation in epilepsy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "medium", "disease": "Epilepsy (childhood)", "glycan_involvement": "Increased agalactosylated glycans (G0), decreased monogalactosylated (G1) and digalactosylated (G2) glycans.", "mechanism": "Decreased galactosylation exposes GlcNAc, activates complement, promotes inflammation, contributing to epilepsy pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9283856" }, { "confidence": "medium", "disease": "Epilepsy (childhood)", "glycan_involvement": "Lower core fucosylation of N-glycans.", "mechanism": "Reduced core fucosylation enhances ADCC, increasing pro-inflammatory responses in epilepsy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Epilepsy (childhood)", "glycan_involvement": "Higher bisected GlcNAc glycans without core fucose.", "mechanism": "Altered bisected GlcNAc structures may modulate ADCC and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Epilepsy (childhood)", "glycan_involvement": "Sialylated N-glycans.", "mechanism": "Sialylation of IgG limits pro-inflammatory effects; no significant difference in total sialylation observed.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "Changes in galactosylation and sialylation.", "mechanism": "Altered IgG N-glycosylation observed in CSF of ALS patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Changes in N-glycan profile.", "mechanism": "Altered IgG N-glycosylation associated with disease state.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Changes in N-glycan profile.", "mechanism": "Altered IgG N-glycosylation observed in patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Altered N-glycosylation.", "mechanism": "Abnormal IgG N-glycan modification associated with disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Lower core fucosylation.", "mechanism": "Decreased IgG fucosylation upregulates ADCC in acute immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9283856" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "O-GlcNAcylation of metabolic proteins", "mechanism": "OGT activity is required for homeostatic regulation of systemic lipid uptake, storage, and release; dysregulation leads to obesity.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC9468787" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "O-GlcNAcylation as a nutrient 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"PMC9468787" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "O-GlcNAcylation of insulin signaling proteins", "mechanism": "Chronic hyperlipidemia-induced O-GlcNAcylation in metabolic tissues impairs insulin signaling.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC9468787" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-GlcNAcylation at specific channel sites", "mechanism": "O-GlcNAcylation of Kv7.3 in AgRP neurons increases excitability and hunger signaling; loss impairs ghrelin response.", "protein": "Kv7.3 potassium channel", "relationship_type": "causal", "source_pmcid": "PMC9468787" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Regulates UDP-GlcNAc synthesis for O-GlcNAcylation", "mechanism": "GFAT activity is increased in obesity, correlating with elevated O-GlcNAcylation in metabolic tissues.", "protein": "GFAT1/GFAT2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9468787" }, { "confidence": "medium", "disease": "Cognitive disorders (e.g., Alzheimer's disease)", "glycan_involvement": "O-GlcNAcylation of neuronal proteins", "mechanism": "Glucose-driven O-GlcNAcylation in neurons is neuroprotective; lipid-induced depression of O-GlcNAcylation may increase vulnerability.", "protein": "OGT", "relationship_type": "protective", "source_pmcid": "PMC9468787" }, { "confidence": "medium", "disease": "\u03b2-cell dysfunction", "glycan_involvement": "O-GlcNAcylation stabilizes translation initiation complex", "mechanism": "O-GlcNAcylation of eIF4G1 is required for proinsulin processing; loss leads to \u03b2-cell dysfunction.", "protein": "eIF4G1", "protein_enriched": { "function": "Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent 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HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several d", "gene_name": "HSD3B7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2F3" }, "relationship_type": "causal", "source_pmcid": "PMC9684675" }, { "confidence": "high", "disease": "Ataxia", "glycan_involvement": "N-glycosylation defects in neural glycoproteins.", "mechanism": "Impaired N-glycosylation affects cerebellar function, leading to ataxia.", "protein": "SRD5A3 (Steroid 5\u03b1-reductase type 3)", "protein_enriched": { "function": "The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. 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Does not metabolize several d", "gene_name": "HSD3B7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2F3" }, "relationship_type": "causal", "source_pmcid": "PMC9684675" }, { "confidence": "high", "disease": "Pigmentary retinopathy", "glycan_involvement": "N-glycosylation defects in retinal proteins.", "mechanism": "Defective glycosylation impacts retinal glycoproteins, leading to pigmentary changes.", "protein": "SRD5A3 (Steroid 5\u03b1-reductase type 3)", "protein_enriched": { "function": "The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. 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Does not metabolize several d", "gene_name": "HSD3B7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2F3" }, "relationship_type": "causal", "source_pmcid": "PMC9684675" }, { "confidence": "high", "disease": "Hypotonia", "glycan_involvement": "N-glycosylation defects in muscle/nerve glycoproteins.", "mechanism": "Glycosylation defects impact neuromuscular function.", "protein": "SRD5A3 (Steroid 5\u03b1-reductase type 3)", "protein_enriched": { "function": "The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several d", "gene_name": "HSD3B7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2F3" }, "relationship_type": "causal", "source_pmcid": "PMC9684675" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "O-GlcNAcylation of multiple hepatic proteins", "mechanism": "OGT-mediated O-GlcNAcylation promotes hepatic fat deposition, inflammation, fibrosis, and tumorigenesis.", "protein": "O-GlcNAc transferase (OGT)", "protein_enriched": { "function": "Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylg", "gene_name": "OGT", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15294" }, "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation stabilizes ChREBP, increasing transcription of lipogenic genes and hepatic triglyceride accumulation.", "protein": "ChREBP", "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "O-GlcNAcylation (indirectly via LXR/OGT)", "mechanism": "O-GlcNAcylation upregulates SREBP-1 expression, promoting lipogenesis and steatosis.", "protein": "SREBP-1", "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "O-GlcNAcylation of p65 subunit", "mechanism": "O-GlcNAcylation activates NF-\u03baB, increasing inflammatory injury in NASH.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation of collagen promotes extracellular matrix deposition and fibrosis.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation of SRF exerts antifibrotic effects by inhibiting hepatic stellate cell activation.", "protein": "Serum response factor (SRF)", "relationship_type": "protective", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation inhibits RIPK3 expression and stability, promoting hepatocyte necroptosis and HCC development.", "protein": "RIPK3", "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation increases LXR activity, upregulating SREBP-1 and promoting lipogenesis.", "protein": "Liver X receptor (LXR)", "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "O-GlcNAcylation", "mechanism": "IP6K1 inhibition reduces O-GlcNAcylation, improving NASH and fibrosis.", "protein": "IP6K1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9688300" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "O-GlcNAcylation", "mechanism": "O-GlcNAcylation of FoxO1 regulates hepatic stellate cell activation and fibrosis.", "protein": "FoxO1", "protein_enriched": { "function": "Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:1589067", "gene_name": "FOXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q12778" }, "relationship_type": "causal", "source_pmcid": "PMC9688300" }, { "confidence": "high", "disease": "Stiff-person syndrome (SPS)", "glycan_involvement": "Glycosylation at Asn38 is not required for autoantibody binding.", "mechanism": "Autoantibodies against GlyR\u03b11 bind to the extracellular domain, leading to receptor internalization, complement activation, and impaired inhibitory neurotransmission.", "protein": "GlyR\u03b11", "relationship_type": "causal", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "PERM", "glycan_involvement": "Binding is independent of glycosylation at Asn38.", "mechanism": "Autoantibodies target GlyR\u03b11, causing receptor dysfunction and neurological symptoms.", "protein": "GlyR\u03b11", "relationship_type": "causal", "source_pmcid": "PMC9969106" }, { "confidence": "medium", "disease": "PERM", "glycan_involvement": "Glycosylation at conserved Asn38 not essential for antibody binding.", "mechanism": "Autoantibodies also target GlyR\u03b12 subunit, contributing to disease pathology.", "protein": "GlyR\u03b12", "relationship_type": "causal", "source_pmcid": "PMC9969106" }, { "confidence": "medium", "disease": "Epileptic encephalopathy", "glycan_involvement": "Detection possible with non-glycosylated GlyR\u03b11 ECD.", "mechanism": "Presence of anti-GlyR\u03b11 autoantibodies in patient serum correlates with disease.", "protein": "GlyR\u03b11", "relationship_type": "biomarker", "source_pmcid": "PMC9969106" }, { "confidence": "medium", "disease": "Focal epilepsy", "glycan_involvement": "Binding independent of glycosylation.", "mechanism": "Anti-GlyR\u03b11 autoantibodies detected in patient serum; possible involvement in pathogenesis.", "protein": "GlyR\u03b11", "relationship_type": "biomarker", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "SPS", "glycan_involvement": "Non-glycosylated ECD is effective for adsorption.", "mechanism": "GlyR\u03b11 ECD can be used to adsorb pathogenic autoantibodies from patient serum, suggesting potential for antibody depletion therapies.", "protein": "GlyR\u03b11", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "PERM", "glycan_involvement": "Non-glycosylated ECD sufficient for autoantibody binding.", "mechanism": "ELISA using non-glycosylated GlyR\u03b11 ECD enables efficient detection and potential removal of autoantibodies.", "protein": "GlyR\u03b11", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969106" }, { "confidence": "medium", "disease": "PERM", "glycan_involvement": "Non-glycosylated ECD used for detection.", "mechanism": "Autoantibodies against GlyR\u03b12 detected in patient serum; supports diagnosis.", "protein": "GlyR\u03b12", "relationship_type": "biomarker", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "SPS", "glycan_involvement": "Non-glycosylated GlyR\u03b11 ECD is suitable for diagnostic assays.", "mechanism": "Detection of anti-GlyR\u03b11 autoantibodies in serum is diagnostic for SPS.", "protein": "GlyR\u03b11", "relationship_type": "biomarker", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "PERM", "glycan_involvement": "Detection does not require glycosylation.", "mechanism": "Anti-GlyR\u03b11 autoantibodies serve as a biomarker for PERM.", "protein": "GlyR\u03b11", "relationship_type": "biomarker", "source_pmcid": "PMC9969106" }, { "confidence": "high", "disease": "Chagas cardiomyopathy", "glycan_involvement": "ICAM-1 is a heavily N-glycosylated cell adhesion molecule; glycosylation modulates its function and stability.", "mechanism": "ICAM-1 expression is increased in myocardial tissue with perfusion defects, reflecting endothelial inflammatory activation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC10000335" }, { "confidence": "medium", "disease": "Chagas cardiomyopathy", "glycan_involvement": "TNF-alpha is glycosylated, which affects its secretion and receptor binding.", "mechanism": "Elevated TNF-alpha mRNA in myocardium correlates with inflammation and perfusion defects.", "protein": "TNF-alpha", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10000335" }, { "confidence": "high", "disease": "Marfan syndrome", "glycan_involvement": "FBN1 is an extracellular glycoprotein; glycosylation is essential for microfibril assembly.", "mechanism": "Pathogenic variants in FBN1 cause Marfan syndrome and predispose to aortic dissection.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "causal", "source_pmcid": "PMC10000335" }, { "confidence": "medium", "disease": "Hereditary thoracic aortic disease", "glycan_involvement": "SMAD3 is glycosylated, which may affect signaling.", "mechanism": "Pathogenic variants in SMAD3 are linked to aortopathy.", "protein": "SMAD3", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84022" }, "relationship_type": "causal", "source_pmcid": "PMC10000335" }, { "confidence": "medium", "disease": "Hereditary thoracic aortic disease", "glycan_involvement": "TGFB2 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "TGFB2 mutations contribute to aortic disease via altered TGF-beta signaling.", "protein": "TGFB2", "relationship_type": "causal", "source_pmcid": "PMC10000335" }, { "confidence": "medium", "disease": "Hereditary thoracic aortic disease", "glycan_involvement": "TGFBR2 is N-glycosylated; glycosylation is important for receptor function.", "mechanism": "TGFBR2 mutations cause syndromic aortopathies.", "protein": "TGFBR2", "protein_enriched": { "function": "Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transdu", "gene_name": "TGFBR2", "glycan_count": 12, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G13694XX", "G37881RL", "G38663NM", "G55412XP", "G56784JY", "G57888GL", "G62461SM", "G57321FI", "G11629QQ", "G22310AV", "G62765YT", "G80920RR" ], "uniprot_id": "P37173" }, "relationship_type": "causal", "source_pmcid": "PMC10000335" }, { "confidence": "high", "disease": "Acute myocardial infarction", "glycan_involvement": "Troponin T is glycosylated; glycosylation may affect assay detection.", "mechanism": "Elevated hs-cTnT is used for early diagnosis and risk stratification in AMI.", "protein": "High-sensitivity cardiac troponin T (hs-cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC10000335" }, { "confidence": "high", "disease": "Congestive heart failure", "glycan_involvement": "Neprilysin is N-glycosylated; glycosylation affects its enzymatic activity.", "mechanism": "Neprilysin inhibitors are guideline-recommended for heart failure therapy.", "protein": "Neprilysin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10000335" }, { "confidence": "medium", "disease": "Congestive heart failure", "glycan_involvement": "N-glycosylation modulates ICAM-1's adhesive properties.", "mechanism": "ICAM-1 upregulation reflects endothelial activation and inflammation in heart failure.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC10000335" }, { "confidence": "high", "disease": "Aortic dissection", "glycan_involvement": "Glycosylation is critical for FBN1 structure and microfibril function.", "mechanism": "FBN1 mutations predispose to aortic dissection via defective connective tissue.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "causal", "source_pmcid": "PMC10000335" }, { "confidence": "high", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Fc glycosylation modulates immune complex formation and complement activation.", "mechanism": "IgG-containing immune complexes deposit in glomeruli, triggering inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10027990" }, { "confidence": "high", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "N-glycosylation affects C3 stability and immune complex binding.", "mechanism": "C3 deposition in glomeruli amplifies inflammatory response.", "protein": "Complement component C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 98, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49955PK", "G69834CE", "G95678HJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10471FG", "G10486CT", "G11115RO", "G14260UH", "G14972EH", "G15664MX", "G17208MA", "G20312EM", "G23294PN", "G23453IV", "G23719VF", "G26330YA", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G32104JU", "G33609NS", "G34029GR", "G34730YF", "G36442WJ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G42124LM", "G46503DX", "G46691LC", "G48414YA", "G49018RC", "G50282JC", "G55220VL", "G57317CE", "G57776ZU", "G59626AS", "G60145BJ", "G61302NC", "G62765YT", "G63041LO", "G64527OM", "G65000LJ", "G65184UU", "G66538GV", "G66676MI", "G67324HN", "G68490OW", "G70101JE", "G70160EA", "G70441OD", "G70619PT", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G76295SF", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84349RE", "G87661QW", "G90575OW", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G96091TT", "G96430BV", "G99679NM", "G22768VO", "G30769VJ", "G31544HA", "G70375MX", "G72398FA", "G78790NZ", "G86234IN", "G90093AU", "G43417UB", "G40702WU", "G49108TO", "G68668TB", "G83161QT" ], "uniprot_id": "P01024" }, "relationship_type": "causal", "source_pmcid": "PMC10027990" }, { "confidence": "medium", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Glycosylation influences C1q binding to IgG.", "mechanism": "C1q binds immune complexes, initiating classical complement pathway.", "protein": "Complement component C1q", "relationship_type": "causal", "source_pmcid": "PMC10027990" }, { "confidence": "medium", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Fc glycosylation of therapeutic antibody affects immune activation.", "mechanism": "Avelumab may trigger immune complex formation and glomerular deposition.", "protein": "Avelumab (anti-PD-L1 antibody)", "relationship_type": "causal", "source_pmcid": "PMC10027990" }, { "confidence": "medium", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Heavily glycosylated spike protein may alter immune recognition.", "mechanism": "Spike protein may be involved in immune complex formation post-infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10027990" }, { "confidence": "medium", "disease": "COVID-19 infection", "glycan_involvement": "Altered glycosylation patterns in COVID-19 may affect immune response.", "mechanism": "IgG response indicates prior or ongoing infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10027990" }, { "confidence": "low", "disease": "COVID-19 infection", "glycan_involvement": "Fc glycosylation impacts antibody effector function.", "mechanism": "Avelumab modulates immune checkpoints, potentially affecting infection outcome.", "protein": "Avelumab (anti-PD-L1 antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10027990" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialic acid recognition and glycosylation of HA modulate infectivity and immune evasion.", "mechanism": "HA mediates viral entry via binding to sialic acid-containing glycans on host cells.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may affect antigenicity and host immune response.", "mechanism": "B6R is essential for viral entry and immune recognition.", "protein": "Envelope protein (B6R)", "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation of NTCP is required for proper folding and surface expression.", "mechanism": "NTCP acts as the cellular receptor for HBV entry into hepatocytes.", "protein": "NTCP", "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation affects antigenicity and secretion.", "mechanism": "HBsAg is used for diagnosis and monitoring of HBV infection.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation modulates secretion and immune tolerance.", "mechanism": "HBeAg indicates active viral replication and infectivity.", "protein": "HBeAg", "relationship_type": "biomarker", "source_pmcid": "PMC10028750" }, { "confidence": "medium", "disease": "Human Bocavirus infection", "glycan_involvement": "Glycosylation may influence tropism and immune evasion.", "mechanism": "VP1-VP2 form the viral capsid and are involved in host cell attachment.", "protein": "VP1-VP2", "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation affects LMP1 stability and signaling.", "mechanism": "LMP1 modulates host gene expression and CpG methylation, promoting carcinogenesis.", "protein": "LMP1", "protein_enriched": { "function": "Acts as a CD40 functional homolog to prevent apoptosis of infected B-lymphocytes and drive their proliferation. Functions as a constitutively active tumor necrosis factor receptor that induces the act", "gene_name": "LMP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03230" }, "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike binding and viral entry.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Spike mediates viral entry and is the main target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10028750" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "VP7 forms the outer capsid and is essential for infectivity.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "causal", "source_pmcid": "PMC10028750" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily N-glycosylated, affecting immune recognition and vaccine efficacy.", "mechanism": "Antibody response to spike protein indicates immune protection against SARS-CoV-2.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC10063368" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation of spike protein may influence immunogenicity and antibody recognition.", "mechanism": "Individuals with schizophrenia show delayed and reduced antibody response to spike protein after vaccination.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC10063368" }, { "confidence": "medium", "disease": "Serious Mental Illness (SMI)", "glycan_involvement": "Glycosylation impacts spike protein antigenicity and vaccine-induced immunity.", "mechanism": "Persons with SMI have delayed vaccine uptake and immune response to spike protein.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC10063368" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Omicron spike protein has altered glycosylation, affecting immune escape.", "mechanism": "Lower antibody levels to Omicron spike protein in schizophrenia, suggesting reduced protection.", "protein": "SARS-CoV-2 Spike protein (Omicron variant)", "relationship_type": "biomarker", "source_pmcid": "PMC10063368" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates vaccine antigenicity and neutralizing antibody binding.", "mechanism": "Target of COVID-19 vaccines to induce protective immunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10063368" }, { "confidence": "high", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "IVIG glycosylation is essential for Fc receptor binding and immunomodulatory effects.", "mechanism": "IVIG is used as first-line therapy to modulate immune response and reduce inflammation in KD.", "protein": "Intravenous Immunoglobulin (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Abciximab is a glycosylated monoclonal antibody; glycosylation affects stability and receptor binding.", "mechanism": "Abciximab inhibits platelet aggregation by blocking glycoprotein IIb/IIIa receptors, used in KD patients with coronary thrombosis.", "protein": "Abciximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "rtPA is N-glycosylated, which affects its plasma half-life and activity.", "mechanism": "rtPA promotes fibrinolysis to dissolve thrombi in KD-related coronary artery thrombosis.", "protein": "Recombinant tissue plasminogen activator (rtPA, alteplase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "IgA Vasculitis (Henoch-Sch\u00f6nlein)", "glycan_involvement": "Aberrant glycosylation of IgA1 is implicated in pathogenesis.", "mechanism": "IgA immune complex deposition in vessels causes vasculitis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC10088797" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity of IVIG.", "mechanism": "Elevated IgG levels may reflect immune activation in KD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10088797" }, { "confidence": "medium", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Glycosylation of IVIG is critical for anti-inflammatory effects.", "mechanism": "IVIG is used to treat MAS complicating KD by modulating cytokine storm.", "protein": "Intravenous Immunoglobulin (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10088797" }, { "confidence": "medium", "disease": "Coronary Artery Aneurysm (CAA)", "glycan_involvement": "Glycosylation affects antibody function and clearance.", "mechanism": "Used to prevent occlusion in KD patients with CAA and thrombosis risk.", "protein": "Abciximab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "Coronary Artery Aneurysm (CAA)", "glycan_involvement": "Fc glycan structure is important for anti-inflammatory activity.", "mechanism": "Early IVIG administration reduces risk of CAA development in KD.", "protein": "Intravenous Immunoglobulin (IVIG)", "relationship_type": "protective", "source_pmcid": "PMC10088797" }, { "confidence": "medium", "disease": "Kawasaki Disease (KD)", "glycan_involvement": "IgA glycosylation may influence immune complex formation.", "mechanism": "Elevated IgA may be associated with KD severity and vascular involvement.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "Coronary Artery Aneurysm (CAA)", "glycan_involvement": "IgG glycosylation is essential for therapeutic efficacy.", "mechanism": "IVIG (IgG) therapy prevents CAA in KD by immune modulation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10088797" }, { "confidence": "high", "disease": "Long COVID-19", "glycan_involvement": "ACE2 glycosylation modulates viral binding and tissue tropism.", "mechanism": "SARS-CoV-2 binds ACE2, leading to cell entry and multi-organ damage.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects antigenicity and immune complex formation.", "mechanism": "Autoantibodies to beta-2-glycoprotein I promote endothelial activation and thrombosis.", "protein": "Beta-2-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation required for ligand binding and function.", "mechanism": "Upregulated in activated endothelium, correlates with thrombosis risk.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation modulates cell adhesion properties.", "mechanism": "Elevated in COVID-19, marks endothelial activation and inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation critical for function.", "mechanism": "Increased expression in COVID-19, associated with vascular inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Potential O-glycosylation may affect extracellular stability.", "mechanism": "Extracellular histone\u2013DNA complexes promote aberrant fibrin formation and coagulopathy.", "protein": "Histones (extracellular)", "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation influences activity and clot structure.", "mechanism": "Increased thrombin generation leads to dense fibrin clots in COVID-19.", "protein": "Thrombin", "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "high", "disease": "Autoimmune complications", "glycan_involvement": "Fc glycosylation modulates effector function and immune complex formation.", "mechanism": "Autoantibodies (IgG) to phospholipids and self-antigens drive autoimmune pathology.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects complement activation.", "mechanism": "IgM autoantibodies to phospholipids activate endothelium and promote thrombosis.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Autoantibodies to cardiolipin-binding proteins form immune complexes, activating endothelium.", "protein": "Cardiolipin-binding proteins", "relationship_type": "causal", "source_pmcid": "PMC10109237" }, { "confidence": "high", "disease": "Anti-MOG antibody-associated demyelinating disease", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG cause demyelination in CNS, leading to neurological and psychiatric symptoms.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10124781" }, { "confidence": "medium", "disease": "Neuropsychiatric manifestations (psychosis, hallucinations, delusions)", "glycan_involvement": "Glycosylation of MOG may modulate immune response and CNS pathology.", "mechanism": "Presence of anti-MOG antibodies is associated with neuropsychiatric symptoms in demyelinating disease.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC10124781" }, { "confidence": "high", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "Glycosylation affects CD14 stability and cell surface expression.", "mechanism": "Increased CD14+ macrophages indicate proinflammatory (M1-like) response in HCV-infected liver.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "high", "disease": "Liver tissue remodeling", "glycan_involvement": "Glycosylation modulates CD163 ligand binding and scavenging function.", "mechanism": "CD163+ macrophages (M2-like) increase post-DAA, associated with anti-inflammatory and tissue repair.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "N-glycosylation critical for HLA-B folding and immune recognition.", "mechanism": "Upregulated in pre-treatment biopsies, reflecting enhanced antigen presentation during infection.", "protein": "HLA-B", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "Glycosylation may affect ISG15 secretion and function.", "mechanism": "Upregulated in pre-treatment biopsies, indicating interferon response to viral infection.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "Potential N-glycosylation affects stability.", "mechanism": "Upregulated in pre-treatment biopsies, part of antiviral response.", "protein": "OAS3", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptos", "gene_name": "OAS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K5" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "Glycosylation may regulate MX1 localization.", "mechanism": "Upregulated in pre-treatment biopsies, mediates antiviral activity.", "protein": "MX1", "protein_enriched": { "function": "Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses. Its target viruses include negative-stranded RNA viruses and HBV through bindin", "gene_name": "MX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20591" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Hepatitis C Virus (HCV) infection", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Upregulated in pre-treatment biopsies, part of interferon-induced antiviral defense.", "protein": "IFIT1", "protein_enriched": { "function": "Plays a key role in the innate immune response as part of an interferon-dependent multiprotein complex, recognizing and sequestering viral RNAs that lack host-specific 2'-O-methylation at their 5' cap", "gene_name": "IFIT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09914" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Chronic liver inflammation", "glycan_involvement": "Heavily glycosylated; glycosylation affects lysosomal targeting.", "mechanism": "CD68+ macrophages increased in inflamed liver tissue.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Chronic liver inflammation", "glycan_involvement": "N-glycosylation modulates Fc receptor function.", "mechanism": "CD16+ macrophages contribute to inflammatory response.", "protein": "CD16 (FCGR3A)", "protein_enriched": { "function": "Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated", "gene_name": "FCGR3A", "glycan_count": 103, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02030ZB", "G05724UK", "G06110VR", "G08146BT", "G10773YW", "G11629QQ", "G11870QZ", "G20218ZS", "G21001NA", "G22310AV", "G22768VO", "G23294PN", "G23432EQ", "G23863VK", "G29880MM", "G32246SI", "G34617SM", "G34730YF", "G37442IW", "G37881RL", "G39188ZX", "G43947VZ", "G44215PV", "G44513XM", "G45495MK", "G45841FE", "G45889JQ", "G48390IG", "G55052CN", "G58232MG", "G61302NC", "G64394MX", "G64527OM", "G67381VP", "G68698AP", "G71569SN", "G72291OX", "G72667IM", "G72735IY", "G72797UR", "G74724QE", "G75983OB", "G80858MF", "G80966KZ", "G81263BG", "G82348BZ", "G82463GQ", "G83295QG", "G83624CJ", "G84452RH", "G84820NF", "G86795LJ", "G91636VS", "G14994KB", "G15169WU", "G91152KU", "G94854LT", "G16208YZ", "G28103WK", "G48488CO", "G57581QG", "G06356OH", "G10133VD", "G13728QT", "G16758MX", "G25418HZ", "G31153XO", "G37868ZX", "G42358LZ", "G48414YA", "G54982TL", "G59536GA", "G70101JE", "G72978AW", "G82830MN", "G93656SY", "G98719SR", "G69834CE", "G03382KH", "G17689DH", "G25520XG", "G26915XM", "G29011JC", "G31916IQ", "G31936TA", "G39213VZ", "G46687AB", "G49874UX", "G55220VL", "G60145BJ", "G62326NX", "G62389NM", "G63381RX", "G70418MS", "G72902CL", "G74430RZ", "G78059CC", "G82119TF", "G90093AU", "G90717TP", "G93141AZ", "G96095QD", "G96771UL" ], "uniprot_id": "P08637" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "medium", "disease": "Persistent inflammatory infiltrates post-DAA", "glycan_involvement": "Glycosylation influences receptor function and anti-inflammatory signaling.", "mechanism": "Persistent CD163+ macrophages indicate ongoing tissue remodeling or unresolved inflammation.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129449" }, { "confidence": "high", "disease": "TP53 mutant triple-negative breast cancer (TNBC)", "glycan_involvement": "No evidence of glycosylation involvement reported.", "mechanism": "Kif11 is essential for survival of TP53 mutant TNBC cells; its inhibition induces mitotic spindle dysfunction and cell death.", "protein": "Kif11", "protein_enriched": { "function": "Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation.", "gene_name": "CARD16", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5EG05" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10129510" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No evidence of glycosylation involvement reported.", "mechanism": "High Kif11 expression is associated with poorer clinical outcomes in TNBC.", "protein": "Kif11", "protein_enriched": { "function": "Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation.", "gene_name": "CARD16", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5EG05" }, "relationship_type": "biomarker", "source_pmcid": "PMC10129510" }, { "confidence": "high", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "E-selectin is a glycoprotein whose function depends on glycosylation for ligand binding.", "mechanism": "Upregulated in ECs-4 endothelial cells during sepsis, mediates leukocyte adhesion and infiltration, contributing to liver inflammation.", "protein": "SELE (E-selectin)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10130477" }, { "confidence": "high", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "CD31 is a heavily glycosylated adhesion molecule; glycosylation affects cell-cell interactions.", "mechanism": "Marker of endothelial cells; loss/decrease correlates with endothelial cell loss and dysfunction in sepsis.", "protein": "CD31 (PECAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "GLUT1 is N-glycosylated, which is essential for its membrane localization and function.", "mechanism": "Upregulated in dysfunctional endothelial cells (ECs-4) during sepsis, indicating metabolic reprogramming.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "biomarker", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "LTA4H is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Highly expressed in Neu-3 neutrophil subset, associated with neutrophil infiltration and liver injury.", "protein": "LTA4H", "protein_enriched": { "function": "Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediat", "gene_name": "LTA4H", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G07755XJ" ], "uniprot_id": "P09960" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "Sortilin is N-glycosylated, which is important for trafficking and function.", "mechanism": "Marker of Neu-3 neutrophil subset, which increases during sepsis and correlates with liver injury.", "protein": "SORT1", "relationship_type": "biomarker", "source_pmcid": "PMC10130477" }, { "confidence": "high", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "ICAM1 glycosylation modulates leukocyte binding.", "mechanism": "Upregulated in ECs-4, mediates neutrophil adhesion and transmigration, promoting inflammation.", "protein": "ICAM1", "relationship_type": "causal", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "VCAM1 glycosylation is required for ligand binding.", "mechanism": "Upregulated in ECs-3, contributes to leukocyte adhesion and endothelial dysfunction.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "SERPINE1 is N-glycosylated; glycosylation affects secretion and activity.", "mechanism": "Upregulated in ECs-4, associated with endothelial dysfunction and pro-thrombotic state.", "protein": "SERPINE1 (PAI-1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "CSF3R is a glycoprotein; glycosylation is important for receptor function.", "mechanism": "Mediates Csf3 signaling between ECs-4 and neutrophils, promoting neutrophil infiltration.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10130477" }, { "confidence": "medium", "disease": "Sepsis-induced acute liver dysfunction", "glycan_involvement": "P-selectin function depends on glycosylation for ligand recognition.", "mechanism": "Upregulated in ECs-4, mediates leukocyte rolling and adhesion, facilitating inflammation.", "protein": "SELP (P-selectin)", "relationship_type": "causal", "source_pmcid": "PMC10130477" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "AQP4-IgG autoantibodies are pathogenic and diagnostic for NMOSD; they target AQP4 on astrocytes.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC10155423" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may influence immune recognition.", "mechanism": "MOG-IgG autoantibodies are found in a subset of NMOSD cases, especially AQP4-seronegative patients.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC10155423" }, { "confidence": "medium", "disease": "Interstitial pulmonary lesion", "glycan_involvement": "Glycosylation of AQP4 may modulate its function and immune targeting.", "mechanism": "AQP4 is highly expressed in lung tissue; autoimmunity may contribute to pulmonary lesions in NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC10155423" }, { "confidence": "medium", "disease": "Venous thromboembolism", "glycan_involvement": "Indirect; glycosylation status may affect AQP4 function in vascular tissues.", "mechanism": "NMOSD patients (often AQP4-IgG positive) have increased risk of venous thromboembolism.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "risk factor", "source_pmcid": "PMC10155423" }, { "confidence": "high", "disease": "Transverse myelitis", "glycan_involvement": "Glycosylation may affect AQP4's immunogenicity.", "mechanism": "AQP4 autoimmunity leads to demyelination and inflammation in spinal cord (transverse myelitis).", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC10155423" }, { "confidence": "high", "disease": "Transverse myelitis", "glycan_involvement": "Glycosylation of MOG influences antibody binding and pathogenicity.", "mechanism": "MOG autoantibodies can cause demyelination in spinal cord, manifesting as transverse myelitis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC10155423" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may affect therapeutic antibody efficacy.", "mechanism": "AQP4 is targeted in immunotherapy for NMOSD (e.g., anti-CD20, complement inhibitors).", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10155423" }, { "confidence": "high", "disease": "Hypertriglyceridemia-induced pancreatitis (HTP)", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Elevated serum lipase indicates pancreatic inflammation.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "IgG response is part of immune defense against SARS-CoV-2.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Deep vein thrombosis", "glycan_involvement": "Glycosylation required for anticoagulant activity.", "mechanism": "Heparin cofactor II inhibits thrombin, reducing clot formation.", "protein": "Heparin cofactor II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Deep vein thrombosis", "glycan_involvement": "N-glycosylation modulates fibrin polymerization.", "mechanism": "Fibrinogen is essential for clot formation; elevated in thrombosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Renal failure", "glycan_involvement": "Glycosylation affects half-life and renal filtration.", "mechanism": "Low serum albumin reflects renal protein loss.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Elevated CK indicates muscle breakdown.", "protein": "Creatine kinase", "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "Glycosylation affects enzyme secretion.", "mechanism": "Elevated AST reflects liver injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Elevated ALT reflects hepatocellular injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10156639" }, { "confidence": "high", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Proinsulin glycosylation affects processing and secretion.", "mechanism": "Insulin infusion corrects hyperglycemia and acidosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Heparin-induced thrombocytopenia", "glycan_involvement": "Glycosylation may influence immunogenicity.", "mechanism": "Heparin exposure can trigger immune-mediated platelet loss.", "protein": "Heparin cofactor II", "relationship_type": "causal", "source_pmcid": "PMC10156639" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "ACE2 glycosylation modulates viral binding and tissue tropism.", "mechanism": "SARS-CoV-2 binds ACE2 on pancreatic cells, potentially triggering inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10156645" }, { "confidence": "medium", "disease": "Diabetes mellitus (new onset)", "glycan_involvement": "Glycosylation of ACE2 affects susceptibility to SARS-CoV-2.", "mechanism": "Viral entry via ACE2 may damage islet cells, impairing insulin secretion.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10156645" }, { "confidence": "medium", "disease": "Diabetes mellitus (new onset)", "glycan_involvement": "Islet cell glycoproteins are targets for immune-mediated damage.", "mechanism": "COVID-19 associated islet cell degeneration leads to impaired insulin production.", "protein": "Islet cell proteins", "relationship_type": "causal", "source_pmcid": "PMC10156645" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation affects lipase secretion and stability.", "mechanism": "Elevated serum lipase indicates pancreatic inflammation in COVID-19.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC10156645" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation modulates amylase activity and clearance.", "mechanism": "Serum amylase increases with pancreatic injury during COVID-19.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC10156645" }, { "confidence": "high", "disease": "Adult T-cell leukemia-lymphoma (ATLL)", "glycan_involvement": "CD25 is a glycoprotein; glycosylation may affect receptor stability and immune recognition.", "mechanism": "CD25 is overexpressed on malignant T-cells in ATLL and used for diagnosis.", "protein": "CD25 (IL2 receptor alpha chain)", "relationship_type": "biomarker", "source_pmcid": "PMC10166224" }, { "confidence": "high", "disease": "Adult T-cell leukemia-lymphoma (ATLL)", "glycan_involvement": "CD3 is glycosylated; glycosylation may influence TCR complex assembly.", "mechanism": "CD3 positivity confirms T-cell lineage in ATLL diagnosis.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC10166224" }, { "confidence": "medium", "disease": "Adult T-cell leukemia-lymphoma (ATLL)", "glycan_involvement": "CD5 is a glycoprotein; glycosylation may modulate cell signaling.", "mechanism": "CD5 expression supports T-cell origin in ATLL.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC10166224" }, { "confidence": "medium", "disease": "Adult T-cell leukemia-lymphoma (ATLL)", "glycan_involvement": "CD2 is glycosylated; glycosylation may affect cell adhesion.", "mechanism": "CD2 positivity is part of immunophenotyping for ATLL.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "biomarker", "source_pmcid": "PMC10166224" }, { "confidence": "medium", "disease": "Adult T-cell leukemia-lymphoma (ATLL)", "glycan_involvement": "CD4 is a glycoprotein; glycosylation impacts receptor function.", "mechanism": "CD4 positivity is characteristic of ATLL malignant cells.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC10166224" }, { "confidence": "medium", "disease": "Burn-induced liver damage", "glycan_involvement": "Albumin is N-glycosylated, which may affect its stability and serum half-life.", "mechanism": "Decreased serum albumin levels reflect liver synthetic dysfunction after burn injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "medium", "disease": "Burn-induced liver damage", "glycan_involvement": "Alkaline phosphatase is heavily N-glycosylated, influencing its secretion and activity.", "mechanism": "Increased serum alkaline phosphatase indicates cholestatic or hepatocellular injury post-burn.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Altered glycosylation may affect albumin function in chronic liver disease.", "mechanism": "Low albumin levels are associated with advanced liver dysfunction in NAFLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation status may modulate enzyme activity.", "mechanism": "Elevated alkaline phosphatase is a marker of liver injury in NAFLD.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "low", "disease": "Primary liver tumors", "glycan_involvement": "Cancer-associated glycoforms may alter albumin clearance.", "mechanism": "Decreased albumin is a prognostic marker in liver cancer.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "low", "disease": "Primary liver tumors", "glycan_involvement": "Tumor-specific glycosylation may affect enzyme isoform distribution.", "mechanism": "Elevated alkaline phosphatase is linked to tumor burden and cholestasis.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "high", "disease": "Burn-induced liver damage", "glycan_involvement": "Both proteins are glycosylated; ratio may reflect combined glycoprotein alterations in liver injury.", "mechanism": "AAPR decreases with worsening liver injury post-burn, correlating better with histological damage than AST/ALT.", "protein": "Albumin to Alkaline Phosphatase Ratio (AAPR)", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Reflects changes in glycoprotein levels due to liver pathology.", "mechanism": "AAPR predicts liver injury and dysfunction more accurately than AST/ALT in NAFLD.", "protein": "Albumin to Alkaline Phosphatase Ratio (AAPR)", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "medium", "disease": "Primary liver tumors", "glycan_involvement": "Altered glycosylation in cancer may impact AAPR.", "mechanism": "AAPR is used to predict liver dysfunction in primary liver tumors.", "protein": "Albumin to Alkaline Phosphatase Ratio (AAPR)", "relationship_type": "biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "high", "disease": "Burn-induced liver damage", "glycan_involvement": "Glycosylation status of both proteins may influence prognostic value.", "mechanism": "Higher AAPR increases likelihood of ICU discharge in burn patients.", "protein": "Albumin to Alkaline Phosphatase Ratio (AAPR)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10185084" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike protein mediates viral entry into host cells via ACE2 receptor binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10186934" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "GCC2 is a Golgi-associated glycoprotein; glycosylation may affect its sorting into EVs and stability.", "mechanism": "sEV-GCC2 levels are elevated in plasma and promote proliferation, tumor growth, and metastasis.", "protein": "GCC2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10187017" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Integrins are heavily glycosylated; glycosylation modulates ligand binding and exosome targeting.", "mechanism": "ITGB3-positive exosome subpopulation increases with CRC progression and promotes proliferation, migration, invasion, and metastasis.", "protein": "ITGB3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Integrin glycosylation affects immune cell interactions and exosome function.", "mechanism": "ITGAM-positive exosome subpopulation (macrophage-derived) suppresses metastatic site development.", "protein": "ITGAM", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (PubMed:2", "gene_name": "ITGAM", "glycan_count": 39, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G80920RR", "G05724UK", "G06110VR", "G28541PG", "G39446WN", "G01650EU", "G23294PN", "G37399XV", "G59626AS", "G72735IY", "G82463GQ", "G95865ZB", "G00912UN", "G06356OH", "G08918WF", "G10486CT", "G27058EU", "G45395BF", "G79666IR", "G39188ZX", "G83460ZZ", "G05962QB", "G70232NH", "G70441OD", "G80479JV", "G93718GY", "G23453IV", "G33609NS", "G57776ZU", "G70223PD", "G92050GC" ], "uniprot_id": "P11215" }, "relationship_type": "protective", "source_pmcid": "PMC10187017" }, { "confidence": "high", "disease": "Acute lung injury", "glycan_involvement": "JAG1 is a glycoprotein; glycosylation is critical for Notch receptor binding.", "mechanism": "EV-mediated presentation of JAG1 activates Notch pathway, restoring endothelial barrier function and reducing edema/permeability.", "protein": "Jagged1 (JAG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "CD63 glycosylation affects EV sorting and immune recognition.", "mechanism": "EVs enriched for CD63 increase with ovarian cancer progression; used for EV isolation and biomarker discovery.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "SHBG is a serum glycoprotein; glycosylation affects hormone binding and stability.", "mechanism": "EV-associated SHBG increases with ovarian cancer progression.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may affect secretion and EV loading.", "mechanism": "EV-associated Carboxypeptidase E increases with ovarian cancer progression.", "protein": "Carboxypeptidase E", "protein_enriched": { "function": "Sorting receptor that directs prohormones to the regulated secretory pathway. Also acts as a prohormone processing enzyme in neuro/endocrine cells, removing dibasic residues from the C-terminal end of", "gene_name": "CPE", "glycan_count": 22, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01650EU", "G02815KT", "G03574QJ", "G06110VR", "G08293MJ", "G09528DL", "G28541PG", "G37399XV", "G41247ZX", "G59626AS", "G59937CP", "G80920RR", "G83555HU", "G00912UN", "G04854VP", "G08918WF", "G44953PJ", "G62765YT", "G68318VE", "G72790NZ", "G83633GK", "G49108TO" ], "uniprot_id": "P16870" }, "relationship_type": "biomarker", "source_pmcid": "PMC10187017" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Many EV proteins are glycosylated, affecting detection and function.", "mechanism": "EV protein fingerprints distinguish Stage I breast cancer from benign/healthy controls.", "protein": "EV-associated proteins (26 identified)", "relationship_type": "biomarker", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Prostate cancer (CRPC)", "glycan_involvement": "Glycosylation may affect EV protein stability and sorting.", "mechanism": "EV RNA/protein cargo reflects clinical status and response to therapy.", "protein": "EV-associated proteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC10187017" }, { "confidence": "medium", "disease": "Hypertension/cardiovascular disease", "glycan_involvement": "Placental EV glycoproteins likely mediate endothelial protection via glycan-dependent mechanisms.", "mechanism": "Placental EVs mitigate hypertension and cardiovascular damage in hypertensive rats.", "protein": "Placental EV glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC10187017" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is an acute phase glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "CRP levels rise in response to inflammation and are used to monitor disease severity and progression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Ferritin is glycosylated; glycosylation may influence its serum half-life.", "mechanism": "Ferritin levels increase in hyperinflammatory states and are associated with poor outcomes.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10202389" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; included for context.", "mechanism": "LDH elevation reflects tissue damage and correlates with disease severity.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "Thromboembolic complications (e.g., DVT, stroke)", "glycan_involvement": "D-dimer is a glycopeptide fragment from fibrinogen; glycosylation affects its detection and clearance.", "mechanism": "Elevated D-dimer indicates increased fibrin degradation and is associated with thrombotic risk in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "Multisystem inflammatory syndrome in children (MIS-C)", "glycan_involvement": "IgG N-glycosylation modulates Fc function and anti-inflammatory activity.", "mechanism": "Elevated anti-SARS-CoV-2 IgG indicates prior infection; IVIG is used as therapy in MIS-C.", "protein": "Immunoglobulin G", "relationship_type": "biomarker/therapeutic", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and affects immune recognition.", "mechanism": "Spike protein mediates viral entry; target of neutralizing antibodies (e.g., casirivimab, imdevimab).", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10202389" }, { "confidence": "medium", "disease": "Hepatorenal syndrome", "glycan_involvement": "Not glycosylated; included for reference.", "mechanism": "Albumin infusion used to manage hypoalbuminemia and volume status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic", "source_pmcid": "PMC10202389" }, { "confidence": "medium", "disease": "Thromboembolic complications", "glycan_involvement": "N-glycosylation affects fibrinogen function and clot formation.", "mechanism": "Fibrinogen is the precursor of fibrin; its degradation produces D-dimer.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation critical for anti-inflammatory effects.", "mechanism": "IVIG used to modulate immune response in severe COVID-19/MIS-C.", "protein": "Immunoglobulin G", "relationship_type": "therapeutic", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates antibody binding and neutralization.", "mechanism": "Targeted by monoclonal antibodies (casirivimab, imdevimab) to block viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10202389" }, { "confidence": "high", "disease": "Human parainfluenza virus infection", "glycan_involvement": "Glycoprotein mediates binding to sialic acid on host cells.", "mechanism": "Baicalin inhibits hemagglutinin-neuraminidase, blocking virus attachment and release.", "protein": "Hemagglutinin-neuraminidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "S protein is heavily glycosylated, mediating receptor binding and immune evasion.", "mechanism": "Tetrandrine, fangchinoline, and cepharanthine inhibit S protein expression, blocking viral entry.", "protein": "S protein (Spike protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "F protein is a type I transmembrane glycoprotein required for fusion.", "mechanism": "Baicalin inhibits F protein expression, preventing viral fusion and entry.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "G protein is a type II glycoprotein involved in host cell attachment and immune modulation.", "mechanism": "Baicalin and acteoside inhibit G protein expression, blocking viral attachment and replication.", "protein": "G protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "Glycosaminoglycans serve as host cell receptors for viral glycoproteins.", "mechanism": "Chebulagic acid and punicalagin interact with glycosaminoglycans, preventing RSV attachment.", "protein": "Glycosaminoglycans", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "medium", "disease": "Human rhinovirus infection", "glycan_involvement": "VP1 is not glycosylated but interacts with host cell surface glycans for attachment.", "mechanism": "Phenylpropanoids bind VP1, inducing conformational changes that block virus-receptor interaction.", "protein": "VP1 capsid protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Neuraminidase is a glycoprotein that cleaves sialic acid from host glycans.", "mechanism": "Plant-derived compounds (e.g., tannins, flavonoids) inhibit neuraminidase, blocking viral release.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Hemagglutinin is a glycoprotein that binds sialic acid on host cells.", "mechanism": "Flavonoids and tannins inhibit hemagglutinin, preventing viral entry.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "Hexon is a major capsid protein; not a glycoprotein but critical for viral structure.", "mechanism": "Astragaloside IV reduces hexon copy number, inhibiting adenovirus replication.", "protein": "Hexon", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "medium", "disease": "Human respiratory syncytial virus infection", "glycan_involvement": "M2-1 is not a glycoprotein but regulates viral transcription.", "mechanism": "Cyclopamine reduces M2-1 expression, inhibiting RSV replication.", "protein": "M2-1 antitermination factor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10204935" }, { "confidence": "high", "disease": "EDTA-induced Pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "Glycosylation maintains GP IIb/IIIa conformation; altered exposure may affect antibody binding.", "mechanism": "EDTA induces dissociation of GP IIb/IIIa, exposing neoepitopes recognized by autoantibodies, leading to platelet clumping and pseudothrombocytopenia.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC10239273" }, { "confidence": "high", "disease": "EDTA-induced Pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "IgG glycosylation affects antibody function and binding.", "mechanism": "EDTA-dependent IgG autoantibodies bind to exposed GP IIb/IIIa, causing platelet aggregation in vitro.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10239273" }, { "confidence": "medium", "disease": "EDTA-induced Pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "IgM glycosylation influences multimerization and antigen binding.", "mechanism": "EDTA-dependent IgM autoantibodies can also mediate platelet clumping.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC10239273" }, { "confidence": "medium", "disease": "EDTA-induced Pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "IgA glycosylation modulates immune complex formation.", "mechanism": "IgA-class antibodies may cause cold agglutination and contribute to PTCP.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC10239273" }, { "confidence": "medium", "disease": "Autoimmune Thrombocytopenia", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies target GP IIb/IIIa, leading to platelet destruction.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10239273" }, { "confidence": "medium", "disease": "EDTA-induced Pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "VWF glycosylation is critical for function and platelet interaction.", "mechanism": "Abciximab inhibits VWF binding to GP IIb/IIIa, associated with PTCP.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10239273" }, { "confidence": "medium", "disease": "Scrub Typhus", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Transient PTCP observed in scrub typhus, possibly via immune-mediated effects on GP IIb/IIIa.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC10239273" }, { "confidence": "low", "disease": "Bladder Cancer", "glycan_involvement": "Cancer-associated glycosylation changes may affect antigenicity.", "mechanism": "PTCP observed in bladder cancer patients, possibly due to altered immune responses to GP IIb/IIIa.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC10239273" }, { "confidence": "low", "disease": "Graves\u2019 Disease", "glycan_involvement": "Autoimmune glycosylation changes may influence antibody binding.", "mechanism": "PTCP reported in Graves\u2019 disease, likely immune-mediated.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC10239273" }, { "confidence": "low", "disease": "SARS-CoV-2 Infection", "glycan_involvement": "Glycosylation may affect immune recognition post-infection.", "mechanism": "PTCP observed post-infection/vaccination, possibly due to immune activation against GP IIb/IIIa.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC10239273" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "IgG glycosylation affects anti-inflammatory activity and Fc\u03b3R binding.", "mechanism": "IVIG blocks immune response and reduces coronary damage in KD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10239295" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Fc\u03b3R glycosylation modulates IgG binding and immune signaling.", "mechanism": "Polymorphisms in Fc\u03b3R are linked to IVIG resistance in KD.", "protein": "Fc gamma receptor (Fc\u03b3R)", "relationship_type": "causal", "source_pmcid": "PMC10239295" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation may affect stability and clearance.", "mechanism": "Elevated CRP indicates systemic inflammation in KD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10239295" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Fibrinogen glycosylation influences clot formation.", "mechanism": "Elevated fibrinogen reflects pro-thrombotic state in KD with aneurysm.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10239295" }, { "confidence": "high", "disease": "ST-elevation acute coronary syndrome (STE-ACS)", "glycan_involvement": "Glycosylation affects receptor function and inhibitor binding.", "mechanism": "Glycoprotein IIb/IIIa inhibitors are used to prevent platelet aggregation during PCI in STE-ACS.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Anti-inflammatory cytokine, may reduce adverse cardiac remodeling.", "protein": "Interleukin-10", "relationship_type": "protective", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation influences TNF secretion and activity.", "mechanism": "Pro-inflammatory cytokine implicated in cardiac dysfunction and remodeling.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "causal", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects leptin secretion and receptor binding.", "mechanism": "Leptin levels correlate with adiposity and metabolic risk.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation modulates peptide stability and bioactivity.", "mechanism": "ANP is released in response to cardiac stretch and is elevated in heart failure.", "protein": "Atrial Natriuretic Peptide (ANP)", "relationship_type": "biomarker", "source_pmcid": "PMC10277532" }, { "confidence": "high", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycosylation may affect drug efficacy.", "mechanism": "Inhibitors reduce thrombotic complications during PCI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Limits vascular inflammation and plaque progression.", "protein": "Interleukin-10", "relationship_type": "protective", "source_pmcid": "PMC10277532" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "Promotes vascular inflammation and plaque instability.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "causal", "source_pmcid": "PMC10277532" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects leptin's vascular effects.", "mechanism": "Leptin promotes vascular inflammation and atherogenesis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC10277532" }, { "confidence": "low", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycosylation influences peptide half-life.", "mechanism": "ANP levels rise acutely in myocardial injury.", "protein": "Atrial Natriuretic Peptide (ANP)", "relationship_type": "biomarker", "source_pmcid": "PMC10277532" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike heavily glycosylated; glycans shield and modulate receptor binding.", "mechanism": "Spike glycoprotein binds to ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10280144" }, { "confidence": "high", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "Glycosylation of spike modulates host interaction and immune evasion.", "mechanism": "Spike protein binds ACE2 on cholangiocytes, leading to cytopathic and immune-mediated injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10280144" }, { "confidence": "high", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "ACE2 is N-glycosylated, affecting spike binding and viral entry.", "mechanism": "ACE2 expression on cholangiocytes mediates susceptibility to SARS-CoV-2 infection.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC10280144" }, { "confidence": "high", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and serum half-life.", "mechanism": "Elevated ALP indicates bile duct injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "AST is glycosylated; glycosylation may affect secretion.", "mechanism": "Elevated AST reflects hepatocellular injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion.", "mechanism": "Elevated ALT reflects hepatocellular injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "LDH is glycosylated; glycosylation may affect serum levels.", "mechanism": "Elevated LDH indicates tissue injury.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "Not applicable.", "mechanism": "UDCA inhibits bile acid absorption and increases bile secretion, reducing cholestatic injury.", "protein": "Ursodeoxycholic acid (UDCA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Post-COVID-19 cholangiopathy", "glycan_involvement": "Not applicable.", "mechanism": "AOBTC used to increase bile flow and reduce injury when UDCA is insufficient.", "protein": "Obeticholic acid (AOBTC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10280144" }, { "confidence": "medium", "disease": "Sclerosing cholangitis", "glycan_involvement": "Spike glycosylation modulates immune recognition and cell entry.", "mechanism": "Spike-ACE2 interaction on cholangiocytes may trigger sclerosing cholangitis.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10280144" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates viral binding affinity.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2 in GI epithelial cells, facilitating infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10280146" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects TMPRSS2 stability and localization.", "mechanism": "TMPRSS2 primes the viral spike protein for cell entry in GI tract.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC10280146" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated, shielding epitopes and modulating host interactions.", "mechanism": "Spike protein binds ACE2 and is activated by TMPRSS2, mediating viral entry into GI cells.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation required for GGT enzymatic activity.", "mechanism": "Elevated GGT indicates cholestatic liver injury in COVID-19 patients.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects ALP stability and secretion.", "mechanism": "Elevated ALP is a marker of liver injury in COVID-19.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation influences AST folding and activity.", "mechanism": "Increased AST reflects hepatocellular damage in COVID-19.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation required for proper ALT function.", "mechanism": "Elevated ALT is indicative of liver injury in COVID-19.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CRP is glycosylated, affecting its solubility and immune function.", "mechanism": "CRP levels correlate with systemic inflammation and disease severity.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates IL6R ligand binding and signaling.", "mechanism": "IL6R targeted by tocilizumab to modulate cytokine storm in severe COVID-19.", "protein": "IL6R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10280146" }, { "confidence": "low", "disease": "Liver injury", "glycan_involvement": "Albumin glycosylation affects ligand binding and transport.", "mechanism": "Altered bilirubin-albumin binding reflects hepatic dysfunction.", "protein": "Albumin (bilirubin carrier)", "relationship_type": "biomarker", "source_pmcid": "PMC10280146" }, { "confidence": "high", "disease": "HBV-related acute-on-chronic liver failure (HBV-ACLF)", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Low antithrombin III activity predicts poor short-term prognosis and increased mortality in HBV-ACLF.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects plasma half-life and anti-inflammatory properties.", "mechanism": "Reduced antithrombin III activity is associated with increased risk and severity of sepsis in liver failure.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "medium", "disease": "Decompensated cirrhosis", "glycan_involvement": "N-glycosylation impacts secretion and activity.", "mechanism": "Lower antithrombin III activity correlates with disease severity and coagulopathy.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Decreased antithrombin III activity is an early predictor of liver failure risk.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "medium", "disease": "Kidney injury (AKI)", "glycan_involvement": "N-glycosylation modulates anti-inflammatory effects.", "mechanism": "Low antithrombin III activity is an independent risk factor for AKI and death in sepsis.", "protein": "Antithrombin III", "relationship_type": "causal/protective", "source_pmcid": "PMC10309089" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation essential for anticoagulant activity.", "mechanism": "Reduced antithrombin III activity increases risk of thrombotic complications in liver failure.", "protein": "Antithrombin III", "relationship_type": "causal/protective", "source_pmcid": "PMC10309089" }, { "confidence": "medium", "disease": "Bleeding complications", "glycan_involvement": "N-glycosylation affects plasma stability.", "mechanism": "Low antithrombin III activity associated with increased bleeding risk due to coagulopathy.", "protein": "Antithrombin III", "relationship_type": "causal/protective", "source_pmcid": "PMC10309089" }, { "confidence": "medium", "disease": "HBV-related acute-on-chronic liver failure (HBV-ACLF)", "glycan_involvement": "Glycosylation required for therapeutic efficacy.", "mechanism": "Exogenous antithrombin III may reduce inflammation and improve prognosis.", "protein": "Antithrombin III", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10309089" }, { "confidence": "low", "disease": "Kidney injury (AKI)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Decreased activity in cirrhosis with AKI, contributing to hypercoagulable state.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "low", "disease": "HBV-related acute-on-chronic liver failure (HBV-ACLF)", "glycan_involvement": "N-glycosylation affects clotting function.", "mechanism": "Fibrinogen levels positively correlate with antithrombin III activity and prognosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10309089" }, { "confidence": "high", "disease": "Beta thalassemia major", "glycan_involvement": "Hepcidin is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Reduced hepcidin levels lead to increased iron absorption and iron overload.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "biomarker", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Hemolytic disease of the fetus and newborn (HDFN)", "glycan_involvement": "IgG glycosylation modulates Fc receptor binding and placental transfer.", "mechanism": "Maternal IgG antibodies against fetal RBC antigens (RhD, Kell, E, c) cross placenta and cause hemolysis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Autoimmune hemolytic anemia (AIHA)", "glycan_involvement": "IgA glycosylation affects immune complex formation and clearance.", "mechanism": "Warm-acting IgA autoantibodies bind RBCs and induce hemolysis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Hemolytic disease of the fetus and newborn (HDFN)", "glycan_involvement": "Kell is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "Maternal anti-K antibodies target fetal RBCs expressing Kell antigen, causing hemolysis.", "protein": "Kell antigen (K)", "protein_enriched": { "function": "Zinc endopeptidase with endothelin-3-converting enzyme activity. Cleaves EDN1, EDN2 and EDN3, with a marked preference for EDN3", "gene_name": "KEL", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G41071NU", "G87661QW" ], "uniprot_id": "P23276" }, "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Hemolytic disease of the fetus and newborn (HDFN)", "glycan_involvement": "RhD is a glycoprotein; glycosylation influences antigen presentation.", "mechanism": "Maternal anti-D antibodies bind fetal RhD-positive RBCs, leading to hemolysis.", "protein": "RhD antigen", "protein_enriched": { "function": "May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane", "gene_name": "RHD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02161" }, "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "medium", "disease": "Immune hemolytic anemia (breast milk-induced)", "glycan_involvement": "RhE glycosylation affects antigenicity and antibody binding.", "mechanism": "Maternal anti-E antibodies in breast milk cause prolonged hemolysis in neonate.", "protein": "E antigen (RhE)", "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "medium", "disease": "Immune hemolytic anemia (breast milk-induced)", "glycan_involvement": "Rhc glycosylation modulates antigenicity.", "mechanism": "Maternal anti-c antibodies in breast milk contribute to neonatal hemolysis.", "protein": "c antigen (Rhc)", "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Transfusion reactions", "glycan_involvement": "A antigen is a glycosylated structure on RBCs; glycan structure determines subgroup.", "mechanism": "Anti-A1 antibodies in non-A1 subgroup patients can cause transfusion incompatibility.", "protein": "A antigen (ABO)", "protein_enriched": { "function": "This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity th", "gene_name": "ABO", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16442" }, "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "medium", "disease": "Transfusion reactions", "glycan_involvement": "M antigen is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "Anti-M antibodies in donors can cause transfusion incompatibility.", "protein": "M antigen", "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "medium", "disease": "Transfusion reactions", "glycan_involvement": "Fya is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "Anti-Fya antibodies can cause hemolytic transfusion reactions.", "protein": "Fya antigen", "relationship_type": "causal", "source_pmcid": "PMC10328111" }, { "confidence": "high", "disease": "Thrombotic Thrombocytopenic Purpura (TTP)", "glycan_involvement": "Glycosylation affects ADAMTS13 secretion and activity.", "mechanism": "Decreased ADAMTS13 activity leads to accumulation of ultra-large VWF multimers, causing microthrombi.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Von Willebrand Disease", "glycan_involvement": "Glycosylation modulates VWF multimerization and function.", "mechanism": "Deficiency or dysfunction of VWF impairs platelet adhesion and clotting.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation required for Factor VIII stability and secretion.", "mechanism": "Deficiency of Factor VIII leads to impaired coagulation and bleeding.", "protein": "Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Graft failure after HSCT", "glycan_involvement": "Glycosylation affects HLA antigenicity and antibody recognition.", "mechanism": "Presence of anti-HLA Class I antibodies increases risk of graft rejection.", "protein": "HLA Class I", "relationship_type": "biomarker", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Platelet refractoriness", "glycan_involvement": "Glycosylation modulates HLA immunogenicity.", "mechanism": "Anti-HLA Class I antibodies cause immune destruction of transfused platelets.", "protein": "HLA Class I", "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Hemolytic transfusion reaction", "glycan_involvement": "Glycosylation of Kidd glycoprotein affects antigenicity.", "mechanism": "Kidd antibodies (IgG) bind complement, causing intra/extravascular hemolysis.", "protein": "Kidd antigen (Jka/Jkb)", "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Hemolytic disease of fetus and newborn (HDFN)", "glycan_involvement": "Glycosylation modulates Kidd antigen expression.", "mechanism": "Maternal Kidd antibodies cross placenta, causing fetal hemolysis.", "protein": "Kidd antigen (Jka/Jkb)", "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "medium", "disease": "Hemolytic transfusion reaction", "glycan_involvement": "Glycosylation influences RhD antigen structure and immune recognition.", "mechanism": "Anti-D antibodies in RhD positive individuals (partial D phenotype) can cause hemolysis.", "protein": "RhD antigen", "protein_enriched": { "function": "May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane", "gene_name": "RHD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02161" }, "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Autoimmune hemolytic anemia in Thalassemia", "glycan_involvement": "Glycosylation required for complement activation and function.", "mechanism": "DAT positivity for C3d indicates complement-mediated hemolysis.", "protein": "Complement C3d", "relationship_type": "biomarker", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Autoimmune hemolytic anemia in Thalassemia", "glycan_involvement": "Fc glycosylation modulates IgG effector function.", "mechanism": "IgG autoantibodies bind RBCs, leading to hemolysis.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10328112" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation may affect EV incorporation and immune recognition.", "mechanism": "PD-L1 on large EVs predicts immunotherapy response, especially in tissue PD-L1-low/negative patients.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation of PD-L1 may modulate its stability and immune interactions.", "mechanism": "EV PD-L1 levels correlate with tumor burden and predict response to anti-PD-1 therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Heparan sulfate glycosylation is essential for GPC1 function and exosome targeting.", "mechanism": "GPC1-positive exosomes serve as a non-invasive diagnostic marker for pancreatic cancer.", "protein": "Glypican-1 (GPC1)", "protein_enriched": { "function": "Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a cataly", "gene_name": "GPC1", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G10486CT", "G27058EU", "G41071NU", "G42124LM", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G66621EA", "G72790NZ", "G80920RR", "G90659AW", "G91636VS", "G95865ZB", "G57321FI", "G43417UB", "G49108TO", "G83460ZZ" ], "uniprot_id": "P35052" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CEA is heavily glycosylated, impacting its detection and immune modulation.", "mechanism": "CEA-positive supermeres and exosomes are diagnostic for colorectal cancer.", "protein": "CEA (CEACAM5)", "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "medium", "disease": "Pan-cancer", "glycan_involvement": "TGFBI glycosylation may affect its secretion and EV association.", "mechanism": "TGFBI-positive supermeres are proposed as pan-cancer detection markers.", "protein": "TGFBI", "protein_enriched": { "function": "Plays a role in cell adhesion (PubMed:8024701). May play a role in cell-collagen interactions (By similarity)", "gene_name": "TGFBI", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q15582" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "PLAP is GPI-anchored and glycosylated, influencing EV targeting.", "mechanism": "PLAP+ EVs are increased in maternal serum during SARS-CoV-2 infection and preeclampsia, indicating placental dysfunction.", "protein": "Placental alkaline phosphatase (PLAP)", "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect Cystatin C stability and EV loading.", "mechanism": "Cystatin C-loaded EVs promote synaptic protection and recovery after ischemic insult.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "EGFR glycosylation modulates receptor function and exosome incorporation.", "mechanism": "EGFR-positive exosomes are diagnostic for glioblastoma.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "PON1 glycosylation may affect HDL association and activity.", "mechanism": "PON1-positive HDL is a highly accurate marker for coronary artery disease.", "protein": "PON1", "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "CD63 is glycosylated; glycosylation may affect EV sorting.", "mechanism": "CD63 is enriched on EVs and used for cancer EV identification.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC10336391" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Albumin glycosylation status may affect its serum stability and function.", "mechanism": "Altered serum albumin levels reflect liver function changes in schizophrenia patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10426400" }, { "confidence": "medium", "disease": "Bipolar Disorder", "glycan_involvement": "Glycosylation may modulate albumin's half-life and binding properties.", "mechanism": "Serum albumin levels are used to monitor liver function in bipolar disorder.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10426400" }, { "confidence": "low", "disease": "Schizo-affective Disorder", "glycan_involvement": "Glycosylation can influence albumin's diagnostic utility.", "mechanism": "Albumin levels indicate liver function status in schizo-affective disorder.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10426400" }, { "confidence": "high", "disease": "Liver Dysfunction", "glycan_involvement": "Altered glycosylation may occur in liver disease, affecting albumin function.", "mechanism": "Decreased albumin is a classic marker of liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10426400" }, { "confidence": "high", "disease": "Metastatic cancer", "glycan_involvement": "Increased glycosyltransferase expression leads to altered glycosylation of FN1, potentially affecting its function in metastasis.", "mechanism": "Overexpression of FN1 in platelet-educated cancer cells enhances migration and proliferation, promoting metastasis.", "protein": "Fibronectin (FN1)", "relationship_type": "causal", "source_pmcid": "PMC10429854" }, { "confidence": "medium", "disease": "Cancer-associated thrombosis (Trousseau\u2019s syndrome)", "glycan_involvement": "Altered glycosylation of FN1 may affect its interaction with platelets and coagulation factors.", "mechanism": "FN1 overexpression may contribute to the hypercoagulable state by modifying the tumor cell-platelet interaction.", "protein": "Fibronectin (FN1)", "relationship_type": "causal", "source_pmcid": "PMC10429854" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22-GP-1 affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against \u03b22-glycoprotein-1 are diagnostic for APS and drive pathogenesis.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "biomarker", "source_pmcid": "PMC10429880" }, { "confidence": "high", "disease": "Venous thrombosis", "glycan_involvement": "Glycosylation modulates \u03b22-GP-1 structure and immune recognition.", "mechanism": "Anti-\u03b22-GP-1 antibodies promote thrombosis by interfering with coagulation and endothelial function.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycan structures influence \u03b22-GP-1 immunogenicity.", "mechanism": "Autoantibodies to \u03b22-GP-1 increase risk of embolic events via hypercoagulability.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "medium", "disease": "Recurrent miscarriage", "glycan_involvement": "Glycosylation may affect placental binding and immune response.", "mechanism": "Anti-\u03b22-GP-1 antibodies disrupt placental function, leading to pregnancy loss.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "medium", "disease": "Cerebrovascular accident (ischemic stroke)", "glycan_involvement": "Glycan modifications affect \u03b22-GP-1's interaction with vascular endothelium.", "mechanism": "Autoantibodies to \u03b22-GP-1 promote cerebral thrombosis.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "low", "disease": "Immune thrombocytopenia", "glycan_involvement": "Glycosylation of platelet glycoproteins influences immune targeting.", "mechanism": "Autoantibodies may target platelet glycoproteins, leading to thrombocytopenia.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "low", "disease": "Autoimmune coagulopathy", "glycan_involvement": "Glycan structures on coagulation proteins modulate immune recognition.", "mechanism": "Autoantibodies disrupt coagulation factors, leading to coagulopathy.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "low", "disease": "Hemorrhagic vasculitis", "glycan_involvement": "Glycosylation affects immune complex formation.", "mechanism": "Immune complexes involving \u03b22-GP-1 contribute to vascular inflammation.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "low", "disease": "Glomerulonephritis", "glycan_involvement": "Glycosylation may influence renal deposition of immune complexes.", "mechanism": "Autoimmune targeting of renal vasculature via \u03b22-GP-1 antibodies.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "low", "disease": "Autoimmune hemolytic anemia", "glycan_involvement": "Glycosylation of erythrocyte surface proteins modulates immune response.", "mechanism": "Autoantibodies may cross-react with erythrocyte glycoproteins.", "protein": "\u03b22-glycoprotein-1", "relationship_type": "causal", "source_pmcid": "PMC10429880" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is heavily glycosylated, affecting antigenicity and immune recognition.", "mechanism": "Target of mRNA vaccine-induced immune response; neutralizing antibodies against S protein confer protection.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10472375" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates antibody binding and immune response.", "mechanism": "Anti-spike IgG titers used as biomarker for vaccine-induced immunity.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "biomarker", "source_pmcid": "PMC10472375" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N protein glycosylation may affect immunogenicity.", "mechanism": "Anti-nucleocapsid IgG indicates prior SARS-CoV-2 infection.", "protein": "Nucleocapsid protein (N protein)", "relationship_type": "biomarker", "source_pmcid": "PMC10472375" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG Fc glycosylation modulates effector functions.", "mechanism": "IgG antibodies against S protein confer immunity post-vaccination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10472375" }, { "confidence": "low", "disease": "Portal vein thrombosis", "glycan_involvement": "No direct evidence, but glycosylation may affect immunogenicity and inflammatory response.", "mechanism": "Rare cases of portal vein thrombosis observed post-mRNA vaccination targeting S protein, especially in predisposed individuals.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal (possible)", "source_pmcid": "PMC10472375" }, { "confidence": "medium", "disease": "Liver transplant rejection/dysfunction", "glycan_involvement": "IgG glycosylation can influence immune activation and rejection risk.", "mechanism": "IgG titers used to monitor immune status in liver transplant recipients post-vaccination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10472375" }, { "confidence": "medium", "disease": "Liver transplant rejection/dysfunction", "glycan_involvement": "Glycosylation of S protein affects immune recognition but not rejection.", "mechanism": "Vaccination-induced anti-spike IgG provides protection without increasing rejection risk.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "protective", "source_pmcid": "PMC10472375" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation sites are critical for antigenicity and vaccine efficacy.", "mechanism": "Booster doses increase anti-spike IgG titers, enhancing protection.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10472375" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antibody detection sensitivity.", "mechanism": "Low anti-N IgG positivity in vaccinated individuals indicates low infection rates.", "protein": "Nucleocapsid protein (N protein)", "relationship_type": "biomarker", "source_pmcid": "PMC10472375" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation may influence half-life and decay rate.", "mechanism": "Decay rate of anti-spike IgG is similar in liver transplant recipients and healthy controls.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10472375" }, { "confidence": "high", "disease": "Bernard-Soulier syndrome", "glycan_involvement": "Glycoprotein Ib-IX-V is a heavily glycosylated complex; glycosylation is essential for its function and surface expression.", "mechanism": "Reduced or absent expression of the glycoprotein Ib-IX-V complex causes defective platelet adhesion and macrothrombocytopenia.", "protein": "Glycoprotein Ib-IX-V receptor complex", "relationship_type": "causal", "source_pmcid": "PMC10523048" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "DPP-4 is a glycoprotein; glycosylation affects its enzymatic activity and stability.", "mechanism": "DPP-4 inhibition by vildagliptin enhances incretin activity, improving glycemic control.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Insulin is glycosylated, affecting its secretion and receptor interaction.", "mechanism": "Insulin secretion and sensitivity are impaired in T2DM; pioglitazone improves insulin sensitivity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547078" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "PPAR\u03b3 activity can be modulated by glycosylation of co-regulators.", "mechanism": "Pioglitazone activates PPAR\u03b3, enhancing insulin sensitivity in peripheral tissues.", "protein": "Peroxisome proliferator-activated receptor gamma (PPAR\u03b3)", "protein_enriched": { "function": "Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) a", "gene_name": "PPARG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "medium", "disease": "\u03b2-cell Dysfunction", "glycan_involvement": "Glycosylation of DPP-4 influences its cell surface expression.", "mechanism": "DPP-4 inhibition improves \u03b1- and \u03b2-cell sensitivity to glucose.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "ALT is glycosylated, which may affect its stability and serum levels.", "mechanism": "ALT levels are elevated in NAFLD; pioglitazone and vildagliptin reduce ALT, indicating improved liver function.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547078" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "AST glycosylation may influence its serum half-life.", "mechanism": "AST levels are elevated in NAFLD; pioglitazone improves AST levels.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547078" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of DPP-4 may affect its interaction with substrates relevant to CV risk.", "mechanism": "DPP-4 inhibition by vildagliptin is associated with no increased risk of CV events.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "PPAR\u03b3 function may be modulated by glycosylation of interacting proteins.", "mechanism": "Pioglitazone activation of PPAR\u03b3 improves liver histology and reduces steatosis.", "protein": "Peroxisome proliferator-activated receptor gamma (PPAR\u03b3)", "protein_enriched": { "function": "Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) a", "gene_name": "PPARG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "low", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation of DPP-4 affects its hepatic activity.", "mechanism": "Vildagliptin may reduce liver glucose production and improve liver enzymes in NAFLD.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547078" }, { "confidence": "low", "disease": "Cardiovascular Disease", "glycan_involvement": "Insulin glycosylation influences its bioactivity and clearance.", "mechanism": "Improved insulin sensitivity reduces CV risk in T2DM patients.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "protective", "source_pmcid": "PMC10547078" }, { "confidence": "high", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "Leptin is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Serum leptin levels are significantly higher in FMS patients and correlate with pain, depression, and disease severity; may contribute to pathogenesis via HPA axis dysregulation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10547486" }, { "confidence": "high", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "IGF-1 is glycosylated; glycosylation affects stability and receptor interaction.", "mechanism": "Serum IGF-1 levels are significantly lower in FMS patients; low IGF-1 is associated with increased pain, depression, and disease duration.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "GH is glycosylated; glycosylation affects secretion and bioactivity.", "mechanism": "GH levels are lower in FMS; GH deficiency may contribute to muscle symptoms and impaired recovery.", "protein": "Growth hormone (GH)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Depression (in FMS context)", "glycan_involvement": "Glycosylation required for leptin's stability and function.", "mechanism": "Leptin levels positively correlate with Beck Depression Inventory scores in FMS patients.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Depression (in FMS context)", "glycan_involvement": "Glycosylation affects IGF-1 function.", "mechanism": "IGF-1 levels negatively correlate with depression scores in FMS patients.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "Glycosylation critical for leptin's bioactivity.", "mechanism": "Leptin's involvement in HPA axis and correlation with clinical severity suggests potential as a therapeutic target.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "Glycosylation impacts IGF-1's therapeutic efficacy.", "mechanism": "GH/IGF-1 axis modulation (e.g., GH therapy) improves FMS symptoms in patients with low IGF-1.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10547486" }, { "confidence": "low", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "IGFBP-3 is glycosylated; glycosylation affects IGF-1 binding.", "mechanism": "IGFBP-3 levels are not significantly different in FMS vs. controls; not a strong biomarker.", "protein": "Insulin-like growth factor binding protein-3 (IGFBP-3)", "relationship_type": "biomarker", "source_pmcid": "PMC10547486" }, { "confidence": "high", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "Glycosylation required for leptin's secretion.", "mechanism": "Leptin levels correlate with pain (VAS), functional disability (FIQ), and tender point count.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC10547486" }, { "confidence": "medium", "disease": "Primary fibromyalgia syndrome (FMS)", "glycan_involvement": "Glycosylation affects IGF-1's stability and function.", "mechanism": "Higher IGF-1 levels are associated with reduced pain and better clinical outcomes in FMS.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "protective", "source_pmcid": "PMC10547486" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "ALT levels are elevated in NAFLD, reflecting hepatocellular injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553467" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is a glycoprotein; glycosylation may modulate activity.", "mechanism": "AST levels are correlated with NAFLD severity, indicating liver damage.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553467" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may influence ALT's serum half-life.", "mechanism": "ALT is correlated with HOMA-IR, indicating metabolic dysfunction.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553467" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect AST's function.", "mechanism": "AST is associated with HOMA-IR, reflecting metabolic stress.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553467" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "VLDL glycosylation affects clearance and receptor binding.", "mechanism": "VLDL levels improved with estrogen therapy, indicating better lipid metabolism.", "protein": "VLDL", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL glycosylation modulates atherogenicity.", "mechanism": "Estrogen therapy reduced LDL, lowering cardiovascular risk.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Insulin glycosylation affects receptor interaction and clearance.", "mechanism": "Estrogen improved fasting insulin and HOMA-IR, enhancing insulin sensitivity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "medium", "disease": "Impaired Glucose Tolerance", "glycan_involvement": "Foxo1 O-glycosylation regulates transcriptional activity.", "mechanism": "Estrogen suppresses gluconeogenesis via Foxo1 modulation.", "protein": "Foxo1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553501" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ER\u03b2 glycosylation modulates receptor stability and signaling.", "mechanism": "Estrogen's hepatoprotective effect is mediated via ER\u03b2 anti-inflammatory signaling.", "protein": "Estrogen Receptor \u03b2", "relationship_type": "protective", "source_pmcid": "PMC10553501" }, { "confidence": "high", "disease": "Liver Dysfunction", "glycan_involvement": "AST glycosylation affects enzyme stability.", "mechanism": "AST levels decreased with estrogen therapy, indicating improved liver function.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "high", "disease": "Liver Dysfunction", "glycan_involvement": "ALT glycosylation influences enzyme activity.", "mechanism": "ALT reduction reflects improved hepatic health post-estrogen therapy.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "medium", "disease": "Hyperbilirubinemia", "glycan_involvement": "Bilirubin transport involves glycoprotein carriers.", "mechanism": "Estrogen therapy reduced total bilirubin, indicating improved hepatic clearance.", "protein": "Total Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALP glycosylation affects secretion and activity.", "mechanism": "No improvement in ALP with estrogen therapy; marker for cholestasis.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL glycosylation modulates anti-atherogenic properties.", "mechanism": "No significant change in HDL with estrogen therapy.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC10553501" }, { "confidence": "high", "disease": "Partial lipodystrophy", "glycan_involvement": "Leptin is a glycoprotein; glycosylation is important for secretion and stability.", "mechanism": "Leptin deficiency or resistance contributes to metabolic abnormalities in lipodystrophy; leptin replacement improves metabolic control.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "high", "disease": "Partial lipodystrophy", "glycan_involvement": "Leptin receptor is glycosylated; glycosylation affects receptor function and ligand binding.", "mechanism": "Leptin receptor activation improves metabolic parameters in lipodystrophy.", "protein": "Leptin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "high", "disease": "Partial lipodystrophy", "glycan_involvement": "As a monoclonal antibody, glycosylation affects stability and receptor interaction.", "mechanism": "Mibavademab (leptin receptor agonist) mimics leptin action, improving metabolic abnormalities.", "protein": "Mibavademab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "high", "disease": "Partial lipodystrophy", "glycan_involvement": "Glycosylation affects immunogenicity and pharmacokinetics.", "mechanism": "Metreleptin (recombinant leptin) is used to treat metabolic complications; neutralizing antibodies can limit efficacy.", "protein": "Metreleptin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "medium", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "Glycosylation required for leptin bioactivity.", "mechanism": "Leptin signaling reduces liver fat content in lipodystrophy.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "Receptor glycosylation modulates signaling.", "mechanism": "Leptin receptor activation lowers triglyceride levels.", "protein": "Leptin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "Antibody glycosylation affects efficacy.", "mechanism": "Mibavademab treatment reduces fasting triglycerides.", "protein": "Mibavademab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553525" }, { "confidence": "low", "disease": "Autoimmune diabetes", "glycan_involvement": "Glycosylation affects leptin stability.", "mechanism": "Leptin levels may be altered in autoimmune diabetes; not a primary therapeutic target here.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553525" }, { "confidence": "high", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Direct involvement; excessive glycogen (a glucose polymer) storage in liver cells.", "mechanism": "Abnormal accumulation of glycogen in hepatocytes leads to hepatomegaly and elevated liver transaminases.", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC10553550" }, { "confidence": "high", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Insulin signaling promotes glycogen synthesis; glycosylation of insulin not directly discussed.", "mechanism": "Insulin increases hepatic glycogen synthesis, contributing to glycogen overload in hepatocytes.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC10553550" }, { "confidence": "medium", "disease": "Lactic Acidosis", "glycan_involvement": "Glycogen accumulation disrupts normal glucose metabolism.", "mechanism": "Excess glycogen storage impairs gluconeogenesis, leading to increased lactate production.", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC10553550" }, { "confidence": "medium", "disease": "Lactic Acidosis", "glycan_involvement": "Indirect; insulin signaling affects glucose and lactate metabolism.", "mechanism": "High insulin and dextrose administration suppress gluconeogenesis, increasing lactate.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC10553550" }, { "confidence": "low", "disease": "Diabetic Ketoacidosis (DKA)", "glycan_involvement": "Glycogen metabolism is altered in DKA.", "mechanism": "Glycogen levels may fluctuate during DKA and its resolution.", "protein": "Glycogen", "relationship_type": "biomarker", "source_pmcid": "PMC10553550" }, { "confidence": "high", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "IGF-2 is a glycoprotein; glycosylation may affect its stability and receptor interactions.", "mechanism": "IGF-2 overproduction by tumor stimulates insulin receptor, causing hypoglycemia.", "protein": "IGF-2", "relationship_type": "causal", "source_pmcid": "PMC10553731" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may influence IGF-2 secretion and half-life.", "mechanism": "Elevated IGF-2/IGF-1 ratio is indicative of HCC-associated NICTH.", "protein": "IGF-2", "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "medium", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "IGF-1 is a glycoprotein; glycosylation affects its bioactivity.", "mechanism": "Suppressed IGF-1 levels due to IGF-2 overproduction.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "medium", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "Proinsulin is glycosylated; glycosylation affects folding and secretion.", "mechanism": "Low proinsulin distinguishes NICTH from insulinoma.", "protein": "Proinsulin", "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "medium", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability.", "mechanism": "Low insulin levels in NICTH compared to insulinoma.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "medium", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "C-peptide is a glycoprotein fragment; glycosylation may affect clearance.", "mechanism": "Low C-peptide helps exclude endogenous hyperinsulinemia.", "protein": "C-Peptide", "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "low", "disease": "Non-islet cell tumor-induced hypoglycemia (NICTH)", "glycan_involvement": "GH glycosylation affects receptor binding.", "mechanism": "Suppressed GH due to IGF-2 overproduction.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Albumin glycosylation status may change in liver disease.", "mechanism": "Low albumin reflects liver dysfunction in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects stability and function.", "mechanism": "Low prealbumin reflects impaired hepatic protein synthesis.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC10553731" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSH indicates thyroid hormone deficiency.", "protein": "TSH (Thyroid Stimulating Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Thyroglobulin is heavily glycosylated, which is essential for its secretion and function.", "mechanism": "Thyroglobulin is a precursor for thyroid hormone synthesis; absence of antibodies suggests non-autoimmune hypothyroidism.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "TPO is glycosylated, affecting its enzymatic activity and immunogenicity.", "mechanism": "Negative TPO antibodies suggest hypothyroidism is not autoimmune.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "high", "disease": "Myxedema coma", "glycan_involvement": "Glycosylation modulates TSH bioactivity and half-life.", "mechanism": "Extremely elevated TSH is diagnostic for severe hypothyroidism/myxedema coma.", "protein": "TSH (Thyroid Stimulating Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "medium", "disease": "Irreversible cardiomyopathy", "glycan_involvement": "Glycosylation of cardiac membrane proteins is essential for contractility and signaling.", "mechanism": "Thyroid hormone deficiency impairs cardiac glycoprotein function, contributing to cardiomyopathy.", "protein": "Cardiac myocyte membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10553740" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Altered glycosylation may affect TSH clearance and activity.", "mechanism": "Persistently high TSH correlates with poor cardiac function.", "protein": "TSH (Thyroid Stimulating Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "medium", "disease": "Myxedema coma", "glycan_involvement": "Glycosylation is critical for thyroglobulin immunogenicity.", "mechanism": "Low/absent thyroglobulin antibodies help exclude autoimmune etiology in myxedema coma.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553740" }, { "confidence": "high", "disease": "IgA nephropathy", "glycan_involvement": "Aberrant glycosylation of IgA1 is implicated in pathogenesis", "mechanism": "Elevated IgA can deposit in glomeruli, causing nephropathy", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC10553745" }, { "confidence": "medium", "disease": "Liver dysfunction (possible autoimmune hepatitis/NASH)", "glycan_involvement": "Altered glycosylation may affect IgA clearance and immune complex formation", "mechanism": "Elevated IgA may reflect immune activation or hepatic inflammation", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553745" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Autoantibodies are glycoproteins; glycosylation affects immune recognition", "mechanism": "Presence indicates autoimmune liver disease", "protein": "Anti-mitochondrial antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10553745" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Glycosylation modulates antibody function", "mechanism": "Presence indicates autoimmune liver disease", "protein": "Smooth muscle antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10553745" }, { "confidence": "low", "disease": "Raynaud\u2019s phenomenon", "glycan_involvement": "Glycosylation may affect IgA immune complex formation", "mechanism": "Elevated IgA may reflect immune dysregulation associated with Raynaud\u2019s", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553745" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Insulin is not heavily glycosylated, but glycosylation can affect receptor interaction", "mechanism": "Insulin used to control glucose levels", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10553745" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation patterns may modulate immune complex formation", "mechanism": "IgA elevation can be seen in SLE flares", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553745" }, { "confidence": "high", "disease": "IgG4-related disease (IgG4-RD)", "glycan_involvement": "IgG4 is a glycoprotein; its glycosylation affects immune function and stability.", "mechanism": "Elevated serum IgG4 and tissue infiltration by IgG4+ plasma cells are diagnostic for IgG4-RD.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC10553760" }, { "confidence": "high", "disease": "Autoimmune pancreatitis", "glycan_involvement": "Glycosylation of IgG4 may modulate immune effector functions in tissue.", "mechanism": "IgG4+ plasma cell infiltration and fibrosis drive pancreatic inflammation.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC10553760" }, { "confidence": "medium", "disease": "Cholangiopathy", "glycan_involvement": "Glycosylation may affect IgG4's interaction with Fc receptors and immune cells.", "mechanism": "IgG4+ plasma cell infiltration leads to biliary duct inflammation and strictures.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC10553760" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation status may influence IgG4's pathogenicity.", "mechanism": "Pancreatic inflammation and fibrosis from IgG4-RD cause endocrine insufficiency and hyperglycemia.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC10553760" }, { "confidence": "medium", "disease": "IgG4-related disease (IgG4-RD)", "glycan_involvement": "CD138 is a heavily glycosylated proteoglycan; glycosylation is essential for plasma cell function.", "mechanism": "CD138 marks mature plasma cells, including IgG4+ cells in tissue infiltrates.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC10553760" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect its serum stability and clearance.", "mechanism": "Elevated serum ferritin is associated with NAFLD and may reflect hepatic inflammation or iron overload.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Transferrin glycosylation status can influence iron binding and transport.", "mechanism": "Elevated transferrin saturation is observed in NAFLD, possibly reflecting altered iron metabolism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its activity and secretion.", "mechanism": "Elevated ALP may indicate liver dysfunction in NAFLD.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation may modulate ferritin's immunogenicity and clearance.", "mechanism": "High ferritin levels are associated with hepatic fibrosis progression.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation impacts transferrin's half-life and receptor binding.", "mechanism": "Altered transferrin saturation may be linked to fibrosis risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Hypogonadism", "glycan_involvement": "Glycosylation may affect ferritin's serum levels.", "mechanism": "Elevated ferritin may be seen in hypogonadism due to metabolic dysregulation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Hypogonadism", "glycan_involvement": "Glycosylation can influence transferrin's function.", "mechanism": "Altered transferrin saturation may reflect metabolic changes in hypogonadism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects ALP's activity.", "mechanism": "Elevated ALP may indicate fibrotic changes in the liver.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Obstructive sleep apnea", "glycan_involvement": "Glycosylation may modulate ferritin's inflammatory properties.", "mechanism": "Elevated ferritin may be secondary to inflammation in sleep apnea.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects transferrin's vascular interactions.", "mechanism": "Altered transferrin saturation may be associated with hypertension in metabolic syndrome.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10553966" }, { "confidence": "high", "disease": "Gestational diabetes insipidus", "glycan_involvement": "Vasopressinase is a glycoprotein; glycosylation is essential for its secretion and stability.", "mechanism": "Placental vasopressinase degrades ADH, leading to gestational DI.", "protein": "Vasopressinase", "relationship_type": "causal", "source_pmcid": "PMC10554040" }, { "confidence": "medium", "disease": "Gestational diabetes insipidus", "glycan_involvement": "ADH is a glycopeptide; glycosylation may affect its stability and recognition by vasopressinase.", "mechanism": "ADH is degraded by placental vasopressinase, reducing its antidiuretic effect.", "protein": "Antidiuretic hormone (ADH)", "relationship_type": "causal (substrate)", "source_pmcid": "PMC10554040" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation of vasopressinase may regulate its activity in pregnancy.", "mechanism": "Increased vasopressinase is associated with preeclampsia.", "protein": "Vasopressinase", "relationship_type": "associated", "source_pmcid": "PMC10554040" }, { "confidence": "low", "disease": "Acute fatty liver of pregnancy", "glycan_involvement": "Glycosylation may affect vasopressinase levels/activity.", "mechanism": "Increased vasopressinase is associated with acute fatty liver of pregnancy.", "protein": "Vasopressinase", "relationship_type": "associated", "source_pmcid": "PMC10554040" }, { "confidence": "low", "disease": "HELLP syndrome", "glycan_involvement": "Glycosylation may affect vasopressinase levels/activity.", "mechanism": "Increased vasopressinase is associated with HELLP syndrome.", "protein": "Vasopressinase", "relationship_type": "associated", "source_pmcid": "PMC10554040" }, { "confidence": "high", "disease": "Gestational diabetes insipidus", "glycan_involvement": "Synthetic analog with modified glycosylation for resistance to degradation.", "mechanism": "DDAVP is resistant to vasopressinase degradation and treats gestational DI.", "protein": "DDAVP (Desmopressin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554040" }, { "confidence": "medium", "disease": "Central diabetes insipidus", "glycan_involvement": "Copeptin is a glycopeptide; glycosylation may affect assay detection.", "mechanism": "Copeptin levels help distinguish central DI from other forms.", "protein": "Copeptin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10554040" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin is a glycoprotein; glycosylation may affect trafficking and binding, but specific glycan changes not detailed.", "mechanism": "Sort_T expression is increased in diabetic adipocytes, impairs insulin-stimulated Glut4 translocation, and reduces glucose uptake.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Sortilin glycosylation may influence vesicle trafficking; not directly addressed.", "mechanism": "Overexpression of Sort_T in non-diabetic adipocytes reduces insulin-stimulated Glut4 translocation and glucose uptake.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10554042" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Sortilin glycosylation status not specified.", "mechanism": "Hyperglycemic conditions promote increased Sort_T levels in non-diabetic adipocytes.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation may affect function; not directly studied.", "mechanism": "GLP-1 and liraglutide decrease Sort_T levels, improving glucose homeostasis in diabetic adipocytes.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554042" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation may affect trafficking; not specified.", "mechanism": "Overexpression of Sort_FL does not rescue glucose uptake in diabetic adipocytes.", "protein": "Sortilin (full-length)", "relationship_type": "neutral", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation may affect detection; not specified.", "mechanism": "Sort_T levels are significantly increased in diabetic adipocytes.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glut4 is a glycoprotein; glycosylation may affect membrane trafficking.", "mechanism": "Impaired Glut4 translocation in diabetic adipocytes leads to reduced glucose uptake.", "protein": "Glucose transporter-4 (Glut4)", "relationship_type": "causal", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation not directly implicated.", "mechanism": "GLP-1 regulates alternative splicing of Sortilin, reducing Sort_T expression via SRSF10.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "GLP-1 regulated", "source_pmcid": "PMC10554042" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation may affect protein-protein interactions.", "mechanism": "Sort_T shows increased co-localization with Glut4 in diabetic adipocytes.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "co-localization", "source_pmcid": "PMC10554042" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Sortilin glycosylation may modulate binding affinity.", "mechanism": "Sort_T binds tightly to Glut4, potentially sequestering it and impairing glucose uptake.", "protein": "Sortilin (truncated splice variant, Sort_T)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "mechanistic", "source_pmcid": "PMC10554042" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect ectodomain release and stability.", "mechanism": "GPNMB ectodomain is released into serum from TSC2-null cells; serum levels are elevated in LAM patients and decrease after Sirolimus treatment.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC10554134" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence antibody binding and ectodomain shedding.", "mechanism": "Antibody-drug conjugate targeting GPNMB abrogates xenograft tumor growth in mouse models.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554134" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may modulate GPNMB's pro-tumorigenic functions.", "mechanism": "GPNMB knockout in TSC2-null cells significantly decreases tumor growth in xenograft models.", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC10554134" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation status may affect protein stability and secretion.", "mechanism": "GPNMB mRNA and protein expression increase under serum starvation (tumor microenvironment mimic), dependent on mTORC1 signaling.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC10554134" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may regulate protease accessibility and ectodomain shedding.", "mechanism": "Inhibition of Adam10/17 proteases (which release GPNMB ectodomain) may mitigate TSC2-null tumor growth.", "protein": "GPNMB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554134" }, { "confidence": "high", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may affect detectability in serum assays.", "mechanism": "Serum GPNMB levels correlate with disease activity and response to Sirolimus treatment.", "protein": "GPNMB", "relationship_type": "biomarker", "source_pmcid": "PMC10554134" }, { "confidence": "medium", "disease": "Lymphangioleiomyomatosis (LAM)", "glycan_involvement": "Glycosylation may influence cell surface localization and function.", "mechanism": "GPNMB promotes cell invasion; siRNA knockdown reduces invasion in vitro.", "protein": "GPNMB", "relationship_type": "causal", "source_pmcid": "PMC10554134" }, { "confidence": "high", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "Dulaglutide is a glycosylated therapeutic protein; glycosylation may affect immunogenicity and clearance.", "mechanism": "Dulaglutide administration led to acute liver injury, likely via idiosyncratic hepatotoxicity.", "protein": "Dulaglutide (GLP-1 receptor agonist)", "relationship_type": "causal", "source_pmcid": "PMC10554152" }, { "confidence": "high", "disease": "Drug-Induced Liver Injury (DILI)", "glycan_involvement": "Glycosylation may modulate hepatic uptake and immune response.", "mechanism": "Dulaglutide identified as the most likely cause of DILI after exclusion of other etiologies.", "protein": "Dulaglutide (GLP-1 receptor agonist)", "relationship_type": "causal", "source_pmcid": "PMC10554152" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "Glycosylation status may influence hepatic metabolism and protein stability.", "mechanism": "ALI induced by dulaglutide resulted in impaired hepatic synthesis of coagulation factors.", "protein": "Dulaglutide (GLP-1 receptor agonist)", "relationship_type": "causal", "source_pmcid": "PMC10554152" }, { "confidence": "medium", "disease": "Alpha-1-antitrypsin deficiency", "glycan_involvement": "Alpha-1-antitrypsin is a glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "Alpha-1-antitrypsin deficiency was excluded as a cause of ALI.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC10554152" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation is critical for secretion and activity of coagulation factors.", "mechanism": "Liver injury led to decreased synthesis of glycosylated coagulation factors, causing coagulopathy.", "protein": "Coagulation factors (e.g., prothrombin)", "relationship_type": "biomarker", "source_pmcid": "PMC10554152" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation enhances stability and half-life of dulaglutide.", "mechanism": "Dulaglutide is used to treat T2DM by stimulating insulin secretion.", "protein": "Dulaglutide (GLP-1 receptor agonist)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554152" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Insulin glycosylation affects stability and detection; intact forms measured by mass spectrometry.", "mechanism": "Elevated II levels correlate with increased liver fat in adolescents with PCOS and obesity.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation status may influence insulin's bioactivity and detection.", "mechanism": "II*ALT combination is a strong predictor of NAFLD, outperforming II or ALT alone.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect immunoassay detection of TI.", "mechanism": "TI*ALT predicts NAFLD but less effectively than II*ALT.", "protein": "Traditional Insulin (TI)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "low", "disease": "NAFLD", "glycan_involvement": "IGF-1 is glycosylated, impacting stability and receptor binding.", "mechanism": "IGF-1 measured but not a significant predictor in this cohort.", "protein": "Insulin-like Growth Factor 1 (IGF-1)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Glycosylation may modulate insulin receptor interaction.", "mechanism": "Elevated II reflects insulin resistance in PCOS adolescents.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation influences insulin clearance and activity.", "mechanism": "Higher II levels associated with obesity-related insulin resistance.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "low", "disease": "NAFLD", "glycan_involvement": "C-peptide is glycosylated, affecting its stability.", "mechanism": "Measured as part of insulin secretion assessment; not a primary predictor.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect age-dependent insulin bioactivity.", "mechanism": "II*ALT is especially predictive in adolescents >15 years old.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Hormonal changes may impact glycosylation patterns.", "mechanism": "Pubertal hormones may alter the II-NAFLD relationship in younger adolescents.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Direct measurement of glycosylated insulin enhances biomarker accuracy.", "mechanism": "Mass spectrometry detection of intact glycosylated insulin improves NAFLD prediction.", "protein": "Intact Insulin (II)", "relationship_type": "biomarker", "source_pmcid": "PMC10554594" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "IAA is a glycoprotein; glycosylation affects stability and immune recognition.", "mechanism": "IAA presence indicates autoimmune attack on pancreatic beta cells.", "protein": "Insulin autoantibody (IAA)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "IA2 autoantibodies are glycoproteins; glycosylation may modulate immunogenicity.", "mechanism": "IA2 autoantibodies are markers of beta cell autoimmunity.", "protein": "Islet antigen-2 autoantibody (IA2)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "GAD autoantibodies are glycoproteins; glycosylation influences immune response.", "mechanism": "GAD autoantibodies are associated with T1D onset.", "protein": "Glutamic acid decarboxylase autoantibody (GAD)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "ICA are glycoproteins; glycosylation may affect antigenicity.", "mechanism": "ICA positivity predicts T1D development.", "protein": "Islet cell autoantibody (ICA)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "ZnT8 autoantibodies are glycoproteins; glycosylation may impact detection.", "mechanism": "ZnT8 autoantibodies are linked to T1D risk.", "protein": "Zinc transporter 8 autoantibody (ZnT8)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Autoimmune thyroid disease", "glycan_involvement": "Anti-TPO is a glycoprotein; glycosylation affects immune complex formation.", "mechanism": "Anti-TPO indicates thyroid autoimmunity.", "protein": "Anti-thyroid peroxidase autoantibody (anti-TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Autoimmune thyroid disease", "glycan_involvement": "Anti-TG is a glycoprotein; glycosylation modulates immunogenicity.", "mechanism": "Anti-TG is a marker for thyroid autoimmunity.", "protein": "Anti-thyroglobulin autoantibody (anti-TG)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Celiac disease", "glycan_involvement": "IgA is a glycoprotein; glycosylation affects function and clearance.", "mechanism": "Anti-transglutaminase IgA is diagnostic for celiac disease.", "protein": "Anti-transglutaminase IgA", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Impaired Glucose Tolerance (IGT)", "glycan_involvement": "IAA glycosylation may influence immune recognition.", "mechanism": "IAA positivity in IGT indicates high risk for progression to T1D.", "protein": "Insulin autoantibody (IAA)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Impaired Glucose Tolerance (IGT)", "glycan_involvement": "ICA glycosylation may affect antigenicity.", "mechanism": "ICA positivity in IGT is predictive of T1D development.", "protein": "Islet cell autoantibody (ICA)", "relationship_type": "biomarker", "source_pmcid": "PMC10554625" }, { "confidence": "medium", "disease": "Cholestasis-induced hypercholesterolemia", "glycan_involvement": "ApoB glycosylation affects LDL metabolism and clearance.", "mechanism": "Elevated ApoB reflects increased LDL due to impaired bile excretion.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC10554643" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome", "glycan_involvement": "Glycosylation modulates enzyme stability and secretion.", "mechanism": "Markedly elevated in cholestatic injury due to bile duct loss.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC10554643" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Elevated GGT indicates cholestatic injury and bile duct damage.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10554643" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome", "glycan_involvement": "Glycosylation affects serum half-life.", "mechanism": "Normal levels help exclude alpha-1 antitrypsin deficiency as a cause.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC10554643" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome", "glycan_involvement": "Glycosylation critical for epithelial integrity and bile duct function.", "mechanism": "Loss of glycoprotein-rich bile duct epithelium leads to cholestasis.", "protein": "Bile duct epithelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10554643" }, { "confidence": "high", "disease": "Graft-versus-host disease (GVHD) of the liver", "glycan_involvement": "LpX is a lipoprotein particle with glycoprotein components; glycosylation may affect its clearance.", "mechanism": "LpX accumulates due to cholestasis in GVHD, leading to abnormal lipid profiles.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "biomarker", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "Cholestatic liver disease", "glycan_involvement": "Glycoprotein components of LpX may be altered in cholestasis.", "mechanism": "LpX forms in cholestasis due to accumulation of bile salts and unesterified cholesterol.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "biomarker", "source_pmcid": "PMC10554693" }, { "confidence": "medium", "disease": "Hyperviscosity syndrome", "glycan_involvement": "Glycosylation may influence LpX aggregation and viscosity.", "mechanism": "LpX can increase serum viscosity, potentially causing hyperviscosity syndrome.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "causal", "source_pmcid": "PMC10554693" }, { "confidence": "medium", "disease": "End-organ ischemia", "glycan_involvement": "Indirect; glycosylation may affect LpX clearance.", "mechanism": "Hyperviscosity from LpX may induce end-organ ischemia.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "causal", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "Graft-versus-host disease (GVHD) of the liver", "glycan_involvement": "ApoB is a glycoprotein; glycosylation affects its function and measurement.", "mechanism": "Low ApoB:Non-HDL-C ratio in GVHD may indicate LpX presence.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "LCAT deficiency", "glycan_involvement": "LCAT is glycosylated; glycosylation affects enzyme activity.", "mechanism": "LCAT deficiency leads to LpX formation due to impaired cholesterol esterification.", "protein": "Lecithin-cholesterol acyl transferase (LCAT)", "relationship_type": "causal", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "LCAT deficiency", "glycan_involvement": "Glycoprotein composition of LpX may be altered in LCAT deficiency.", "mechanism": "LpX is found in LCAT deficiency due to abnormal lipid metabolism.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "biomarker", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "Cholestatic liver disease", "glycan_involvement": "Glycosylation may affect LpX stability and clearance.", "mechanism": "LpX formation is a direct result of cholestasis.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "causal", "source_pmcid": "PMC10554693" }, { "confidence": "medium", "disease": "Cholestatic liver disease", "glycan_involvement": "ApoB glycosylation affects its plasma levels and detection.", "mechanism": "Low ApoB levels with high non-HDL cholesterol suggest LpX in cholestatic liver disease.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC10554693" }, { "confidence": "medium", "disease": "Graft-versus-host disease (GVHD) of the liver", "glycan_involvement": "Glycosylation may affect LpX removal efficiency.", "mechanism": "LpX can be acutely treated by plasma exchange or apheresis if hyperviscosity occurs.", "protein": "Lipoprotein-X (LpX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10554693" }, { "confidence": "high", "disease": "Type 1 Diabetes (T1D)", "glycan_involvement": "Increased glycation (non-enzymatic addition of glucose to hemoglobin).", "mechanism": "Reflects chronic hyperglycemia via non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Increased glycation (non-enzymatic addition of glucose to hemoglobin).", "mechanism": "Reflects chronic hyperglycemia via non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Reflects systemic glycation status.", "mechanism": "Elevated HbA1c is associated with increased risk of NAFLD in diabetes.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects clearance and function.", "mechanism": "Elevated LDL is associated with NAFLD and metabolic syndrome.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties.", "mechanism": "Low HDL is a feature of metabolic syndrome and NAFLD.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects lipoprotein metabolism.", "mechanism": "Elevated triglycerides are associated with NAFLD and metabolic syndrome.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10554775" }, { "confidence": "high", "disease": "Microvascular complications", "glycan_involvement": "Reflects chronic protein glycation.", "mechanism": "High HbA1c predicts risk of microvascular complications in diabetes.", "protein": "Hemoglobin A1c", "relationship_type": "causal", "source_pmcid": "PMC10554775" }, { "confidence": "high", "disease": "Henoch-Schonlein Purpura (HSP)", "glycan_involvement": "IgA glycosylation affects immune complex formation and clearance.", "mechanism": "IgA immune complex deposition in small vessels triggers vasculitis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC10555049" }, { "confidence": "medium", "disease": "Lactic acidosis", "glycan_involvement": "Glycosylation affects hemoglobin stability and function.", "mechanism": "Hemoglobin levels reflect oxygen carrying capacity, relevant in tissue hypoxia and acidosis.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555119" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation modulates lipase secretion and activity.", "mechanism": "Elevated lipase indicates pancreatic involvement in multi-organ dysfunction.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555119" }, { "confidence": "low", "disease": "Septic shock", "glycan_involvement": "Glycosylation influences troponin stability and detection.", "mechanism": "Troponin elevation may indicate cardiac stress in septic shock.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555119" }, { "confidence": "low", "disease": "Acute kidney failure", "glycan_involvement": "Glycosylation regulates transporter localization and function.", "mechanism": "Elevated ammonia reflects impaired renal clearance.", "protein": "Ammonia transporter (generic)", "relationship_type": "biomarker", "source_pmcid": "PMC10555119" }, { "confidence": "high", "disease": "Postmenopausal breast cancer", "glycan_involvement": "Aberrant mucin glycosylation and abundance promote carcinogenesis.", "mechanism": "Obesity increases Mucin-1 abundance in breast tumors, which is associated with carcinogenesis.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10555144" }, { "confidence": "medium", "disease": "Postmenopausal breast cancer", "glycan_involvement": "Altered glycosylation patterns in Mucin-1 in tumors.", "mechanism": "Tumor Mucin-1 abundance positively correlates with patient BMI.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555144" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSI is an autoantibody with glycosylated Fc regions affecting immune function.", "mechanism": "TSI stimulates the TSH receptor, causing hyperthyroidism.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "Autoantibody glycosylation modulates immune complex formation.", "mechanism": "TG AB is elevated in autoimmune thyroid diseases.", "protein": "Thyroglobulin Antibody (TG AB)", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "Glycosylation affects antibody effector function.", "mechanism": "Autoantibody against thyroid peroxidase, indicating thyroid autoimmunity.", "protein": "Thyroid Peroxidase Antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Systemic Sclerosis", "glycan_involvement": "Glycosylation influences autoantibody pathogenicity.", "mechanism": "SCL-70 autoantibody is associated with systemic sclerosis.", "protein": "SCL-70 (Topoisomerase I antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "medium", "disease": "Primary Biliary Cirrhosis", "glycan_involvement": "Autoantibody glycosylation may affect disease association.", "mechanism": "SCL-70 can be present in primary biliary cirrhosis.", "protein": "SCL-70 (Topoisomerase I antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "medium", "disease": "Lupus Erythematosus", "glycan_involvement": "Glycosylation may modulate immune complex formation.", "mechanism": "SCL-70 can be seen in lupus erythematosus.", "protein": "SCL-70 (Topoisomerase I antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Liver Enzyme Elevation", "glycan_involvement": "Alkaline phosphatase is a glycoprotein; glycosylation affects stability and clearance.", "mechanism": "Elevated in liver dysfunction and cholestasis.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "medium", "disease": "Liver Enzyme Elevation", "glycan_involvement": "Possible glycosylation may affect serum half-life.", "mechanism": "Elevated in hepatocellular injury.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "medium", "disease": "Liver Enzyme Elevation", "glycan_involvement": "Possible glycosylation may affect serum half-life.", "mechanism": "Elevated in hepatocellular injury.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation modulates antibody-receptor interactions.", "mechanism": "TSI causes excessive thyroid hormone production.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC10555166" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "PCSK9 is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "PCSK9 regulates LDL receptor degradation, influencing serum LDL-cholesterol levels.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555206" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Evolocumab is an IgG2 glycoprotein; glycosylation affects stability and efficacy.", "mechanism": "Evolocumab binds PCSK9, preventing LDL receptor degradation and lowering LDL-cholesterol.", "protein": "Evolocumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10555206" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "Possible immune-mediated reaction due to glycosylation patterns of monoclonal antibody.", "mechanism": "Evolocumab administration coincided with acute liver enzyme elevation (transaminitis).", "protein": "Evolocumab", "relationship_type": "causal", "source_pmcid": "PMC10555206" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates PCSK9 activity in metabolic disease.", "mechanism": "PCSK9 levels are associated with metabolic syndrome and diabetes risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555206" }, { "confidence": "low", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may affect PCSK9 secretion in steatotic liver.", "mechanism": "PCSK9 expression is altered in fatty liver disease.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555206" }, { "confidence": "low", "disease": "Malignant melanoma", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Transaminitis triggered by evolocumab led to discovery of melanoma metastasis.", "protein": "Evolocumab", "relationship_type": "biomarker", "source_pmcid": "PMC10555206" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Loss of hepatic IPMK protein increases hepatic steatosis and triglyceride accumulation, promoting NAFLD progression.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "causal", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Loss of hepatic IPMK augments steatohepatitis, increases pro-inflammatory gene expression, and exacerbates liver injury.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "causal", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Restoration or upregulation of hepatic IPMK (e.g., via time-restricted feeding) alleviates NAFLD symptoms.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Increasing hepatic IPMK expression (e.g., via time-restricted feeding) reduces hepatic triglyceride accumulation, inflammation, and fibrosis.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555226" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Decreased hepatic IPMK protein levels correlate with NAFLD severity in diet-induced mouse models.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555226" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "Lower hepatic IPMK protein levels are associated with increased liver injury markers (ALT, AST) and fibrosis.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555226" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "IPMK maintains hepatic insulin signaling and suppresses gluconeogenesis, protecting against NAFLD.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "protective", "source_pmcid": "PMC10555226" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "IPMK suppresses hepatic inflammation and fibrosis, protecting against NASH progression.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "protective", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "IPMK deficiency increases hepatic triglyceride accumulation and pro-inflammatory gene expression.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "causal", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Not directly addressed in this article.", "mechanism": "IPMK deficiency exacerbates liver injury, fibrosis, and inflammation in NASH models.", "protein": "Inositol polyphosphate multikinase (IPMK)", "protein_enriched": { "function": "Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)", "gene_name": "IP6K2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHH9" }, "relationship_type": "causal", "source_pmcid": "PMC10555226" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSH glycosylation affects its stability and receptor binding.", "mechanism": "TSH is suppressed in Graves' disease due to autoantibody stimulation of TSH receptor.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "high", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation of carrier proteins affects FT3 transport.", "mechanism": "Elevated FT3 is a marker of thyroid storm severity.", "protein": "Free Triiodothyronine (FT3)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "high", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation of carrier proteins affects FT4 transport.", "mechanism": "Elevated FT4 is a marker of thyroid storm.", "protein": "Free Thyroxine (FT4)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "Glycosylation of thyroxine-binding globulin modulates TT4 levels.", "mechanism": "High TT4 is characteristic of Graves' disease.", "protein": "Total Thyroxine (TT4)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "high", "disease": "Thyroid storm", "glycan_involvement": "Glycosylation of carrier proteins affects TT3 transport.", "mechanism": "High TT3 is seen in thyroid storm.", "protein": "Total Triiodothyronine (TT3)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "ALP glycosylation affects its secretion and activity.", "mechanism": "Elevated ALP indicates cholestatic liver injury.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "medium", "disease": "Cholestatic hepatitis", "glycan_involvement": "Albumin glycosylation affects bilirubin binding and clearance.", "mechanism": "Elevated bilirubin is a marker of cholestatic hepatitis.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC10555248" }, { "confidence": "medium", "disease": "Hypercalcemia in pregnancy", "glycan_involvement": "PTHrP is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "Endogenous PTHrP production by breast and placental tissue can increase serum calcium.", "protein": "Parathyroid hormone-related protein (PTHrP)", "protein_enriched": { "function": "Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport (PubMed:12538599, PubMed", "gene_name": "PTHLH", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "P12272" }, "relationship_type": "causal", "source_pmcid": "PMC10555366" }, { "confidence": "low", "disease": "Hypercalcemia in pregnancy", "glycan_involvement": "Glycosylation is essential for placental protein function and secretion.", "mechanism": "Placental glycoproteins may contribute to maternal hypercalcemia, as suggested by rapid correction post-delivery.", "protein": "Placental glycoproteins (general)", "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC10555366" }, { "confidence": "low", "disease": "Acute fatty liver of pregnancy (AFLP)", "glycan_involvement": "Glycosylation may modulate PTHrP activity in pregnancy.", "mechanism": "Case report suggests possible link between AFLP and increased PTHrP or placental glycoprotein activity.", "protein": "Parathyroid hormone-related protein (PTHrP)", "protein_enriched": { "function": "Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport (PubMed:12538599, PubMed", "gene_name": "PTHLH", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "P12272" }, "relationship_type": "association (rare)", "source_pmcid": "PMC10555366" }, { "confidence": "high", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "Aldosterone is a steroid hormone, not glycosylated; however, its measurement is used in context with glycoprotein assays.", "mechanism": "Elevated plasma aldosterone is a hallmark of PA and predicts incomplete biochemical success after adrenalectomy.", "protein": "Plasma aldosterone", "relationship_type": "biomarker", "source_pmcid": "PMC10555406" }, { "confidence": "high", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "Cortisol is not glycosylated; used as a reference in glycoprotein-based assays.", "mechanism": "Cortisol levels are used to normalize aldosterone measurements (A/C ratio) to predict surgical outcomes.", "protein": "Cortisol", "relationship_type": "biomarker", "source_pmcid": "PMC10555406" }, { "confidence": "medium", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "Renin is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Low plasma renin activity is associated with incomplete biochemical success after surgery.", "protein": "Plasma renin", "relationship_type": "biomarker", "source_pmcid": "PMC10555406" }, { "confidence": "medium", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "ACTH receptor is glycosylated, which may affect ligand binding and signaling.", "mechanism": "ACTH stimulation test assesses aldosterone secretory capacity, predicting long-term outcome.", "protein": "Adrenocorticotropic hormone receptor (ACTH receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC10555406" }, { "confidence": "medium", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "CYP11B2 is glycosylated, which may influence enzyme activity.", "mechanism": "Overactivity leads to aldosterone overproduction in PA.", "protein": "Aldosterone synthase (CYP11B2)", "relationship_type": "causal", "source_pmcid": "PMC10555406" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "N-glycosylation is essential for TSH secretion, stability, and receptor interaction.", "mechanism": "TSH levels are elevated in hypothyroidism due to loss of negative feedback from thyroid hormones.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC10555437" }, { "confidence": "medium", "disease": "Autoimmune Thyroiditis", "glycan_involvement": "N-glycosylation of TPO may affect antigenicity and autoantibody recognition.", "mechanism": "Anti-TPO antibodies are markers of autoimmune thyroid destruction leading to hypothyroidism.", "protein": "Thyroid Peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC10555437" }, { "confidence": "medium", "disease": "Myxedema Madness (Hypothyroidism-induced Psychosis)", "glycan_involvement": "N-glycosylation modulates TSH bioactivity and half-life.", "mechanism": "Profoundly elevated TSH indicates severe hypothyroidism, which can manifest as psychosis.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC10555437" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins are heavily glycosylated, affecting platelet function and clearance.", "mechanism": "Platelet count, reflecting platelet glycoprotein levels, is used in the FIB-4 score to assess risk of liver fibrosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10555677" }, { "confidence": "high", "disease": "Autoimmune hypoglycemia (Hirata's syndrome)", "glycan_involvement": "Insulin is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "Autoantibodies bind endogenous insulin, prolonging its half-life and causing hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC10555778" }, { "confidence": "high", "disease": "Autoimmune hypoglycemia (Hirata's syndrome)", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects antibody function.", "mechanism": "Presence of anti-insulin antibodies is diagnostic for autoimmune hypoglycemia.", "protein": "Anti-insulin autoantibody", "relationship_type": "biomarker", "source_pmcid": "PMC10555778" }, { "confidence": "medium", "disease": "Autoimmune hypoglycemia (Hirata's syndrome)", "glycan_involvement": "Receptor glycosylation modulates insulin binding and signaling.", "mechanism": "Insulin receptor signaling is dysregulated due to abnormal insulin-antibody complexes.", "protein": "Insulin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555778" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "Glycosylation may influence insulin clearance and immune recognition.", "mechanism": "Excess circulating insulin (due to antibody binding) causes hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC10555778" }, { "confidence": "high", "disease": "Autoimmune hypoglycemia (Hirata's syndrome)", "glycan_involvement": "C-peptide is not glycosylated.", "mechanism": "Elevated C-peptide indicates endogenous insulin secretion.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555778" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Semaglutide is a glycopeptide; glycosylation increases stability and bioavailability.", "mechanism": "Improves glycemic control by enhancing insulin secretion and reducing glucagon secretion.", "protein": "GLP-1 receptor agonist (semaglutide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555779" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation enhances peptide stability for oral administration.", "mechanism": "Promotes weight loss via appetite suppression and delayed gastric emptying.", "protein": "GLP-1 receptor agonist (semaglutide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555779" }, { "confidence": "medium", "disease": "Mixed Dyslipidemia", "glycan_involvement": "Glycosylation supports peptide function and pharmacokinetics.", "mechanism": "Improves lipid profile by reducing triglycerides and LDL, increasing HDL.", "protein": "GLP-1 receptor agonist (semaglutide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555779" }, { "confidence": "medium", "disease": "Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation critical for peptide stability and efficacy.", "mechanism": "Reduces hepatic steatosis and improves liver enzymes.", "protein": "GLP-1 receptor agonist (semaglutide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555779" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation enables effective systemic delivery.", "mechanism": "Reduces cardiovascular risk factors (weight, glucose, lipids, blood pressure).", "protein": "GLP-1 receptor agonist (semaglutide)", "relationship_type": "protective", "source_pmcid": "PMC10555779" }, { "confidence": "high", "disease": "Thyroid Storm", "glycan_involvement": "TSH glycosylation affects its stability and receptor binding.", "mechanism": "Low TSH levels indicate hyperthyroid state and thyroid storm.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC10555815" }, { "confidence": "medium", "disease": "Graves' Disease", "glycan_involvement": "TSH receptor glycosylation modulates autoantibody binding.", "mechanism": "Autoantibodies stimulate TSH receptor, driving hyperthyroidism.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC10555815" }, { "confidence": "high", "disease": "Myopericarditis", "glycan_involvement": "Glycosylation may affect troponin I clearance and detection.", "mechanism": "Elevated troponin I reflects myocardial injury in myopericarditis.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555815" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "TSH glycosylation influences hormone half-life.", "mechanism": "Low TSH in thyroid storm is associated with heart failure risk.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC10555815" }, { "confidence": "medium", "disease": "Arrhythmia (Atrial Fibrillation)", "glycan_involvement": "TSH glycosylation impacts hormone activity.", "mechanism": "Hyperthyroidism (low TSH) increases risk of atrial fibrillation.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC10555815" }, { "confidence": "low", "disease": "Pericardial Disease", "glycan_involvement": "TSH glycosylation may modulate immune response.", "mechanism": "Thyrotoxicosis can precipitate pericardial inflammation.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC10555815" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may affect troponin I stability.", "mechanism": "Elevated troponin I indicates myocardial damage in heart failure.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555815" }, { "confidence": "low", "disease": "Arrhythmia (Atrial Fibrillation)", "glycan_involvement": "Glycosylation may influence troponin I detection.", "mechanism": "Troponin I elevation may accompany arrhythmia due to myocardial stress.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10555815" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Indirect; glycosylated hemoglobin is a glycan-based biomarker.", "mechanism": "Spexin levels correlate with fasting/postprandial glucose, glycosylated hemoglobin, and HOMA index.", "protein": "Spexin (Neuropeptide Q)", "protein_enriched": { "function": "Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to", "gene_name": "NPW", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N729" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555926" }, { "confidence": "medium", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Not specified.", "mechanism": "Spexin infusion ameliorates ALT and AST levels, suggesting hepatoprotective effects.", "protein": "Spexin (Neuropeptide Q)", "protein_enriched": { "function": "Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to", "gene_name": "NPW", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N729" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10555926" }, { "confidence": "low", "disease": "Adult Growth Hormone Deficiency (aGHD)", "glycan_involvement": "Not specified.", "mechanism": "Spexin plasma levels are similar in aGHD and controls; no significant role as a biomarker in aGHD.", "protein": "Spexin (Neuropeptide Q)", "protein_enriched": { "function": "Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to", "gene_name": "NPW", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N729" }, "relationship_type": "biomarker", "source_pmcid": "PMC10555926" }, { "confidence": "low", "disease": "Metabolic Syndrome", "glycan_involvement": "Not specified.", "mechanism": "Spexin may help differentiate aGHD from metabolic syndrome due to its controversial role in metabolic impairment.", "protein": "Spexin (Neuropeptide Q)", "protein_enriched": { "function": "Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to", "gene_name": "NPW", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N729" }, "relationship_type": "differentiation marker", "source_pmcid": "PMC10555926" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and secretion.", "mechanism": "Insulin secretion is altered in T2DM; spexin blunts reciprocal secretion with insulin via paracrine effects.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10555926" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "PD1 is glycosylated; glycosylation affects its stability and ligand binding.", "mechanism": "Blockade of PD1 increases T cell activation, leading to beta-cell autoimmunity.", "protein": "PD1", "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "CTLA4 glycosylation modulates surface expression and immune regulation.", "mechanism": "Blockade of CTLA4 enhances immune activation, promoting beta-cell destruction.", "protein": "CTLA4", "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "IL21R is glycosylated; glycosylation is required for receptor function.", "mechanism": "Genetic blockade of IL21R protects against ICI-induced diabetes.", "protein": "IL21R", "protein_enriched": { "function": "DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:1", "gene_name": "NHEJ1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H9Q4" }, "relationship_type": "protective", "source_pmcid": "PMC10556985" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "ICOS glycosylation regulates ligand binding and T cell activation.", "mechanism": "ICOS+ Tfh/Tph cells secrete IL-21, driving CD8+ T cell-mediated beta-cell destruction.", "protein": "ICOS", "protein_enriched": { "function": "Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response (PubMed:9930702). Upon binding to its ligand ICOSL expressed on antigen p", "gene_name": "ICOS", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "Q9Y6W8" }, "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "CXCR5 glycosylation affects chemokine binding and cell trafficking.", "mechanism": "CXCR5+ Tfh cells contribute to IL-21 secretion and autoimmune activation.", "protein": "CXCR5", "protein_enriched": { "function": "Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph ", "gene_name": "CXCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P32302" }, "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "Granzyme B is glycosylated; glycosylation influences secretion and activity.", "mechanism": "Granzyme B+ CD8+ T cells mediate cytotoxicity against beta-cells.", "protein": "Granzyme B", "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "IFN\u03b3 glycosylation affects secretion and stability.", "mechanism": "IFN\u03b3+ CD8+ T cells promote inflammatory destruction of beta-cells.", "protein": "IFN\u03b3", "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (ICI-T1DM)", "glycan_involvement": "CXCR6 glycosylation modulates chemokine interactions.", "mechanism": "CXCR6+ CD8+ T cells are expanded and contribute to autoimmune mediator phenotype.", "protein": "CXCR6", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL16. Used as a coreceptor by SIVs and by strains of HIV-2 and m-tropic HIV-1", "gene_name": "CXCR6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O00574" }, "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "high", "disease": "Immune-related adverse events (IRAEs)", "glycan_involvement": "PD1 glycosylation regulates immune checkpoint function.", "mechanism": "PD1 blockade leads to multi-organ autoimmunity.", "protein": "PD1", "relationship_type": "causal", "source_pmcid": "PMC10556985" }, { "confidence": "high", "disease": "Insulinitis", "glycan_involvement": "IL21R glycosylation is essential for receptor signaling.", "mechanism": "IL21R deficiency reduces insulinitis index in ICI-treated mice.", "protein": "IL21R", "protein_enriched": { "function": "DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:1", "gene_name": "NHEJ1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H9Q4" }, "relationship_type": "protective", "source_pmcid": "PMC10556985" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "N-glycosylation modulates fibrinogen function and plasma stability.", "mechanism": "FGB variants affect coagulation and thrombosis risk, influencing stroke susceptibility.", "protein": "Fibrinogen beta chain (FGB)", "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "O-glycosylation of NOTCH receptor modulates ligand binding and signaling.", "mechanism": "NOTCH signaling regulates vascular development and inflammation, impacting stroke risk.", "protein": "NOTCH", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Predicted N-glycosylation may affect cell adhesion properties.", "mechanism": "NINJ2 involved in nerve regeneration and vascular integrity, associated with stroke risk.", "protein": "NINJ2", "protein_enriched": { "function": "Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis (PubMed:24120868). In ribosome biogenesis, may also play a role in rRNA", "gene_name": "NOP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZM5" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "MTHFR variants alter homocysteine metabolism, increasing stroke risk.", "protein": "MTHFR", "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Large artery atherosclerosis", "glycan_involvement": "Potential O-glycosylation may modulate nuclear localization.", "mechanism": "HDAC9 regulates vascular smooth muscle cell proliferation and inflammation.", "protein": "HDAC9", "protein_enriched": { "function": "Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an importa", "gene_name": "HDAC9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UKV0" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect membrane association.", "mechanism": "ALOX5AP involved in leukotriene biosynthesis, promoting vascular inflammation.", "protein": "ALOX5AP", "protein_enriched": { "function": "P4-ATPase flippase which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetr", "gene_name": "ATP8B3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60423" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation may affect enzyme activity.", "mechanism": "CYP4A11 regulates fatty acid metabolism, influencing vascular tone and stroke risk.", "protein": "CYP4A11", "protein_enriched": { "function": "Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX and participates to the sixth step in", "gene_name": "CPOX", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P36551" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Potential glycosylation may regulate protein stability.", "mechanism": "PDE4D modulates cAMP signaling in vascular cells, affecting stroke susceptibility.", "protein": "PDE4D", "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Cardioembolism", "glycan_involvement": "Potential glycosylation may affect transcriptional activity.", "mechanism": "ZFHX3 variants linked to atrial fibrillation, increasing cardioembolic stroke risk.", "protein": "ZFHX3", "protein_enriched": { "function": "Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta s", "gene_name": "ZFHX3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15911" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "medium", "disease": "Hemorrhagic Stroke", "glycan_involvement": "N-glycosylation impacts fibrinogen function in hemostasis.", "mechanism": "Altered FGB levels may influence bleeding risk and vessel integrity.", "protein": "Fibrinogen beta chain (FGB)", "relationship_type": "biomarker", "source_pmcid": "PMC10586545" }, { "confidence": "high", "disease": "Autoimmune encephalitis (LGI1-related)", "glycan_involvement": "Glycosylation of LGI1 may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against LGI1 disrupt synaptic function, leading to limbic encephalitis.", "protein": "LGI1", "protein_enriched": { "function": "", "gene_name": "C1orf74", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96LT6" }, "relationship_type": "causal", "source_pmcid": "PMC10586546" }, { "confidence": "high", "disease": "Autoimmune encephalitis (CASPR2-related)", "glycan_involvement": "Glycosylation modulates CASPR2 structure and immune recognition.", "mechanism": "Autoantibodies against CASPR2 impair neuronal signaling, causing encephalitis and peripheral nerve hyperexcitability.", "protein": "CASPR2", "relationship_type": "causal", "source_pmcid": "PMC10586546" }, { "confidence": "medium", "disease": "Paraneoplastic cerebellar degeneration (PCA2)", "glycan_involvement": "Targets glycoprotein antigens on Purkinje cells; glycosylation may influence epitope presentation.", "mechanism": "PCA2 autoantibody is associated with paraneoplastic cerebellar degeneration, often linked to lung carcinoma.", "protein": "Anti-Purkinje Cell Antibody 2 (PCA2)", "relationship_type": "biomarker", "source_pmcid": "PMC10586546" }, { "confidence": "high", "disease": "Myasthenia gravis", "glycan_involvement": "AChR glycosylation affects receptor stability and immune recognition.", "mechanism": "Autoantibodies against AChR impair neuromuscular transmission.", "protein": "Acetylcholine Receptor (AChR)", "protein_enriched": { "function": "Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane", "gene_name": "CHRNA1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G09724ZC", "G22573RC", "G22768VO", "G34499SX", "G55220VL", "G63337SS", "G68668TB" ], "uniprot_id": "P02708" }, "relationship_type": "causal", "source_pmcid": "PMC10586546" }, { "confidence": "medium", "disease": "Myasthenia gravis", "glycan_involvement": "MuSK is a glycoprotein; glycosylation may modulate antibody binding.", "mechanism": "Autoantibodies against MuSK disrupt NMJ formation and function.", "protein": "MuSK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10586546" }, { "confidence": "high", "disease": "Primary CNS lymphoma (PCNSL)", "glycan_involvement": "IL-10 is glycosylated, which may affect its stability and detection.", "mechanism": "Elevated CSF IL-10 reflects malignant B cell activity and is a diagnostic/prognostic marker.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC10586546" }, { "confidence": "medium", "disease": "Atypical Parkinsonism with NMJ involvement", "glycan_involvement": "Glycosylation of AChR may influence autoantibody binding.", "mechanism": "Anti-AChR antibodies detected in atypical parkinsonism suggest NMJ autoimmune overlap.", "protein": "AChR", "relationship_type": "biomarker", "source_pmcid": "PMC10586546" }, { "confidence": "high", "disease": "Glanzmann thrombasthenia", "glycan_involvement": "Integrin glycosylation affects surface expression and function.", "mechanism": "Loss of \u03b1IIb\u03b23 impairs platelet aggregation, causing bleeding.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10589886" }, { "confidence": "high", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation modulates ligand binding and drug targeting.", "mechanism": "Anti-\u03b1IIb\u03b23 agents inhibit platelet aggregation, reducing thrombosis.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10589886" }, { "confidence": "high", "disease": "Arterial thrombosis", "glycan_involvement": "GPVI is N-glycosylated, affecting receptor stability and ligand binding.", "mechanism": "GPVI blockade inhibits thrombosis without affecting haemostasis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10589886" }, { "confidence": "medium", "disease": "Obesity (severe)", "glycan_involvement": "Altered glycosylation may affect GPVI surface expression.", "mechanism": "High GPVI levels and platelet hyperactivation observed in severe obesity.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "biomarker", "source_pmcid": "PMC10589886" }, { "confidence": "medium", "disease": "Vascular diseases", "glycan_involvement": "CD93 is a C-type lectin; glycosylation critical for function.", "mechanism": "CD93 regulates platelet activation via PAR4; deficiency impairs aggregation.", "protein": "CD93", "relationship_type": "causal", "source_pmcid": "PMC10589886" }, { "confidence": "medium", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation may regulate JAM-A localization and interactions.", "mechanism": "JAM-A suppresses platelet activation; phosphorylation modulates function.", "protein": "Junctional Adhesion Molecule-A (JAM-A)", "protein_enriched": { "function": "", "gene_name": "CTAG1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P78358" }, "relationship_type": "protective", "source_pmcid": "PMC10589886" }, { "confidence": "high", "disease": "Congenital thrombocytopenia", "glycan_involvement": "Glycosylation may affect G6b-B surface expression and signaling.", "mechanism": "Loss of G6b-B causes macrothrombocytopenia, MK expansion, myelofibrosis.", "protein": "G6b-B", "protein_enriched": { "function": "Plays a role in the cellular response to UV irradiation. Mediates G2/M cell cycle arrest, MEK autoactivation and ERK1/2-signaling pathway activation in response to UV irradiation. In ciliated cells of", "gene_name": "NEK10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6ZWH5" }, "relationship_type": "causal", "source_pmcid": "PMC10589886" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "P-selectin glycosylation is essential for ligand binding.", "mechanism": "Platelet P-selectin promotes leukocyte adhesion, facilitating plaque formation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10589886" }, { "confidence": "medium", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation affects integrin function and ligand interaction.", "mechanism": "\u03b15\u03b21 mediates platelet adhesion to fibronectin but is dispensable for thrombosis.", "protein": "Integrin \u03b15\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10589886" }, { "confidence": "medium", "disease": "Congenital thrombocytopenia", "glycan_involvement": "GPVI glycosylation may affect complex stability.", "mechanism": "G6b-B deficiency leads to loss of GPVI-FcR\u03b3 complex, contributing to thrombocytopenia.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC10589886" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency (AATD)", "glycan_involvement": "ADAM-17 is a glycoprotein; glycosylation may affect its activity and secretion.", "mechanism": "ADAM-17 levels are significantly higher in severe AATD (ZZ phenotype), suggesting a role in pathogenesis via cleavage of cytokines and receptors.", "protein": "ADAM-17", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "high", "disease": "Pulmonary emphysema", "glycan_involvement": "Glycosylation is essential for alpha-1-antitrypsin stability and function.", "mechanism": "Alpha-1-antitrypsin inhibits ADAM-17 and other pro-inflammatory molecules, reducing risk of emphysema.", "protein": "Alpha-1-antitrypsin", "relationship_type": "protective", "source_pmcid": "PMC10601095" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "TFPI2 is a secreted glycoprotein; glycosylation may affect its stability and biomarker utility.", "mechanism": "TFPI2 expression is upregulated in TNFa-treated UC cell models and may predict non-response to Infliximab.", "protein": "TFPI2", "relationship_type": "biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "JAM-A glycosylation may modulate cell adhesion and signaling.", "mechanism": "JAM-A regulates HER2/HER3 expression; its cleavage is a biomarker of resistance to HER2-targeted therapies.", "protein": "JAM-A", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "medium", "disease": "Pelizaeus-Merzbacher disease (PMD)", "glycan_involvement": "Claudin-11 is a glycoprotein; glycosylation may affect folding and ER stress response.", "mechanism": "Mutant claudin-11 induces ER stress and sensitizes cells to ER stress-induced death, contributing to leukodystrophy.", "protein": "Claudin-11", "relationship_type": "causal", "source_pmcid": "PMC10601095" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "HER2 glycosylation affects receptor dimerization and drug response.", "mechanism": "HER2 expression regulated by JAM-A; resistance to HER2-targeted therapy linked to JAM-A cleavage.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10601095" }, { "confidence": "low", "disease": "Ulcerative colitis", "glycan_involvement": "E-selectin glycosylation is critical for leukocyte adhesion.", "mechanism": "SELE expression is upregulated in TNFa-treated UC cell models, but not statistically significant as a biomarker.", "protein": "SELE (E-selectin)", "relationship_type": "biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "low", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation modulates Fc receptor function.", "mechanism": "FCGR3B expression is upregulated in TNFa-treated UC cell models, but not statistically significant.", "protein": "FCGR3B", "protein_enriched": { "function": "Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cy", "gene_name": "FCGR3B", "glycan_count": 40, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G60177UT", "G82830MN", "G03382KH", "G05724UK", "G06110VR", "G17689DH", "G22310AV", "G23432EQ", "G23863VK", "G25520XG", "G26915XM", "G29011JC", "G31916IQ", "G31936TA", "G39188ZX", "G39213VZ", "G46687AB", "G49874UX", "G55220VL", "G60145BJ", "G62326NX", "G62389NM", "G63381RX", "G64527OM", "G70418MS", "G72291OX", "G72667IM", "G72797UR", "G72902CL", "G74430RZ", "G78059CC", "G80858MF", "G82119TF", "G84452RH", "G90093AU", "G90717TP", "G91636VS", "G93141AZ", "G96095QD", "G96771UL" ], "uniprot_id": "O75015" }, "relationship_type": "biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "low", "disease": "Ulcerative colitis", "glycan_involvement": "FGFR2 glycosylation affects receptor signaling.", "mechanism": "FGFR2 is downregulated in TNFa-treated UC cell models; may be involved in disease phenotype.", "protein": "FGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis", "gene_name": "FGFR2", "glycan_count": 7, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G40574BA", "G59626AS", "G80920RR", "G43417UB", "G10256JP", "G62765YT", "G86182NS" ], "uniprot_id": "P21802" }, "relationship_type": "biomarker", "source_pmcid": "PMC10601095" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "HER3 glycosylation affects receptor function.", "mechanism": "HER3 expression regulated by JAM-A; may contribute to drug resistance.", "protein": "HER3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10601095" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation regulates membrane association, possibly affecting signaling.", "mechanism": "Overexpression promotes cell proliferation via Erk1/2, Akt, c-Myc, and CDK pathways; inhibits p53 and Rb tumor suppressors.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Glycosylation required for membrane association and possibly oncogenic function.", "mechanism": "Overexpression enhances pro-survival signaling and inhibits apoptosis.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "high", "disease": "Stomach (gastric) cancer", "glycan_involvement": "Glycosylation status may influence subcellular localization and function.", "mechanism": "Overexpression correlates with tumorigenesis; regulated by circTMC5/miR-361-3p axis.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylated form associates with membrane, possibly modulating signaling.", "mechanism": "Promotes tumor progression via Akt and c-Myc pathways; knockout slows tumor growth.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may affect protein stability and localization.", "mechanism": "Overexpression linked to poor prognosis and enhanced proliferation.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "medium", "disease": "Esophageal cancer", "glycan_involvement": "Glycosylation may regulate protein-protein interactions.", "mechanism": "Interacts with tumor suppressors (ECRG2, p19 ARF); overexpression promotes tumorigenesis.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10622986" }, { "confidence": "high", "disease": "Malignant peripheral nerve sheath tumor (MPNST)", "glycan_involvement": "Glycosylation required for membrane association, possibly affecting oncogenic signaling.", "mechanism": "Drives tumor growth; targeting RBEL1A or downstream CDK inhibits tumor progression.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB6C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0N0" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC10622986" }, { "confidence": "medium", "disease": "Drug resistance in cancer", "glycan_involvement": "Glycosylation may influence RBEL1A stability and function in resistance.", "mechanism": "Overexpression correlates with resistance to cisplatin/oxaliplatin via p53 inhibition.", "protein": "RBEL1A (Rab-like protein 1A)", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. 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As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10623000" }, { "confidence": "high", "disease": "Leukocyte adhesion deficiency type II (LAD II)", "glycan_involvement": "Global loss of fucosylation on cell surface glycoproteins.", "mechanism": "Hereditary deficiency of SLC35C1 leads to loss of fucosylated glycans, causing LAD II.", "protein": "SLC35C1 (GDP-fucose transporter)", "protein_enriched": { "function": "Antiporter specific for GDP-l-fucose and depending on the concomitant reverse transport of GMP. Involved in GDP-fucose import from the cytoplasm into the Golgi lumen", "gene_name": "SLC35C1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96A29" }, "relationship_type": "causal", "source_pmcid": "PMC10623000" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Fucosylation loss increases \u03b2-TrCP expression via EGFR/ERK pathway inhibition.", "mechanism": "Upregulation of \u03b2-TrCP promotes PD-L1 ubiquitination and degradation, suppressing LUAD cell proliferation.", "protein": "\u03b2-TrCP", "protein_enriched": { "function": "Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubM", "gene_name": "BTRC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y297" }, "relationship_type": "protective", "source_pmcid": "PMC10623000" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Indirect; regulated by PD-L1 which is stabilized by fucosylation.", "mechanism": "PD-L1 expression maintains cyclin E levels, promoting cell cycle progression and proliferation.", "protein": "Cyclin E", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G1/S (start) transition", "gene_name": "CCNE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24864" }, "relationship_type": "causal", "source_pmcid": "PMC10623000" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Indirect; regulated by PD-L1 stability.", "mechanism": "PD-L1 expression maintains cyclin B1 levels, promoting cell cycle progression.", "protein": "Cyclin B1", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G2/M (mitosis) transition", "gene_name": "CCNB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14635" }, "relationship_type": "causal", "source_pmcid": "PMC10623000" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Fucosylation stabilizes PD-L1; loss leads to increased ubiquitination and degradation.", "mechanism": "Loss of PD-L1 (via knockdown or fucosylation inhibition) suppresses LUAD cell proliferation and migration.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC10623000" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "N-glycosylation (fucosylation) required for full receptor activity.", "mechanism": "EGFR signaling is essential for LUAD cell growth; its function is modulated by fucosylation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10623000" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against AQP4 cause astrocyte damage and CNS demyelination.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)", "glycan_involvement": "MOG is glycosylated; glycan structures may influence immune recognition.", "mechanism": "Anti-MOG antibodies target MOG on oligodendrocytes, leading to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "Area Postrema Syndrome (APS) in NMOSD", "glycan_involvement": "Glycosylation may modulate AQP4 localization and immune targeting.", "mechanism": "AQP4 autoantibodies cause selective loss of AQP4 in area postrema, leading to nausea/vomiting.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC10637578" }, { "confidence": "medium", "disease": "Paraneoplastic Neurological Syndrome (PNS)", "glycan_involvement": "CASPR2 is glycosylated; glycan moieties may affect antibody binding.", "mechanism": "Anti-CASPR2 antibodies are associated with PNS and autoimmune encephalitis.", "protein": "CASPR2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "medium", "disease": "Paraneoplastic Neurological Syndrome (PNS)", "glycan_involvement": "CDR2 is glycosylated; glycosylation may influence immune response.", "mechanism": "Anti-Yo antibodies target CDR2, leading to cerebellar degeneration in PNS.", "protein": "Yo antigen (CDR2)", "protein_enriched": { "function": "", "gene_name": "CDR2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01850" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "medium", "disease": "Paraneoplastic Neurological Syndrome (Anti-Ma2 Encephalitis)", "glycan_involvement": "PNMA2 is glycosylated; glycan structures may affect antigenicity.", "mechanism": "Anti-Ma2 antibodies cause limbic and diencephalic encephalitis.", "protein": "Ma2 antigen (PNMA2)", "protein_enriched": { "function": "May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis", "gene_name": "MPLKIP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TAP9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "Myasthenia Gravis", "glycan_involvement": "AChR is glycosylated; glycosylation affects receptor function and immune recognition.", "mechanism": "Autoantibodies against AChR impair neuromuscular transmission.", "protein": "Acetylcholine Receptor (AChR)", "protein_enriched": { "function": "Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane", "gene_name": "CHRNA1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G09724ZC", "G22573RC", "G22768VO", "G34499SX", "G55220VL", "G63337SS", "G68668TB" ], "uniprot_id": "P02708" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "Autoimmune Encephalitis", "glycan_involvement": "IgG glycosylation modulates effector function and pathogenicity.", "mechanism": "Pathogenic IgG autoantibodies mediate neuronal damage.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "NMOSD (Relapse Prevention)", "glycan_involvement": "Glycosylation of AQP4 may affect antibody binding and therapy response.", "mechanism": "Rituximab reduces anti-AQP4 IgG, preventing relapses.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "MOGAD (Relapse Prevention)", "glycan_involvement": "MOG glycosylation may influence immune targeting and therapy efficacy.", "mechanism": "Immunosuppressants reduce anti-MOG antibody-mediated relapses.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10637578" }, { "confidence": "high", "disease": "Congenital Myasthenic Syndromes (CMS)", "glycan_involvement": "Defective O-mannosylation of glycoproteins critical for neuromuscular junction function.", "mechanism": "GMPPB mutations impair glycosylation of proteins at the neuromuscular junction, leading to defective synaptic transmission.", "protein": "GMPPB", "protein_enriched": { "function": "Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, diff", "gene_name": "DDR1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q08345" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "high", "disease": "Congenital Myasthenic Syndromes (CMS)", "glycan_involvement": "Glycosylation required for proper receptor folding and surface expression.", "mechanism": "Mutations in the glycoprotein acetylcholine receptor epsilon subunit disrupt receptor assembly/function.", "protein": "CHRNE", "protein_enriched": { "function": "After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane", "gene_name": "CHRNE", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G22573RC", "G22768VO", "G81315DD" ], "uniprot_id": "Q04844" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "medium", "disease": "Congenital Myasthenic Syndromes (CMS)", "glycan_involvement": "Glycosylation affects stability and localization of COLQ at the neuromuscular junction.", "mechanism": "COLQ mutations impair anchoring of acetylcholinesterase at the synapse.", "protein": "COLQ", "protein_enriched": { "function": "Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues", "gene_name": "CRTAP", "glycan_count": 22, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G02815KT", "G05049YU", "G05724UK", "G15664MX", "G31852PQ", "G39188ZX", "G41247ZX", "G46687AB", "G62765YT", "G64527OM", "G70101JE", "G70441OD", "G72747WU", "G80920RR", "G83633GK", "G90659AW", "G06110VR", "G14260UH", "G46503DX", "G47702MW", "G62894KT" ], "uniprot_id": "O75718" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "medium", "disease": "Congenital Myasthenic Syndromes (CMS)", "glycan_involvement": "Glycosylation may influence transporter trafficking and function.", "mechanism": "Mutations affect vesicular acetylcholine transporter function, impacting neurotransmission.", "protein": "SLC18A3", "protein_enriched": { "function": "Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles. Uses the electrochemical pr", "gene_name": "SLC18A3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q16572" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "high", "disease": "CADASIL", "glycan_involvement": "NOTCH3 is highly glycosylated; glycan modifications affect receptor signaling and aggregation.", "mechanism": "Mutations in NOTCH3 glycoprotein cause vascular smooth muscle degeneration.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "medium", "disease": "CARASIL", "glycan_involvement": "HTRA1 is a secreted glycoprotein; glycosylation may affect secretion and function.", "mechanism": "HTRA1 mutations lead to loss of protease activity, causing small vessel disease.", "protein": "HTRA1", "protein_enriched": { "function": "Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3", "gene_name": "HTRA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92743" }, "relationship_type": "causal", "source_pmcid": "PMC10637580" }, { "confidence": "high", "disease": "Anti-GAD65 antibody-associated Cerebellar Ataxia", "glycan_involvement": "GAD65 is glycosylated; glycan epitopes may influence autoantibody binding.", "mechanism": "Autoantibodies against GAD65 (a glycoprotein) are associated with immune-mediated cerebellar ataxia.", "protein": "Anti-GAD65 antibody", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10637580" }, { "confidence": "high", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and serum half-life.", "mechanism": "Serum albumin levels correlate with liver function and predict suboptimal hepatobiliary phase MRI images in CLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "high", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "Conjugation involves glycosyltransferase activity in hepatocytes.", "mechanism": "Elevated direct bilirubin is strongly associated with suboptimal hepatobiliary phase MRI images in CLD.", "protein": "Direct Bilirubin (conjugated)", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "N-glycosylation status may affect albumin function in disease.", "mechanism": "Low serum albumin predicts poor imaging quality for HCC detection in MRI.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Reflects impaired glycoprotein-mediated hepatic excretion.", "mechanism": "High direct bilirubin is a predictor of suboptimal MRI for HCC evaluation.", "protein": "Direct Bilirubin (conjugated)", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its secretion and activity.", "mechanism": "ALP levels correlate with biliary excretion and MRI image quality.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "Serum proteins include glycoproteins; glycosylation affects serum protein stability.", "mechanism": "Lower total protein is associated with suboptimal MRI imaging in CLD.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function.", "mechanism": "Platelet count correlates with liver function and MRI image quality.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Pancreaticobiliary Disease", "glycan_involvement": "Glycosylation modulates ALP activity in biliary tract.", "mechanism": "ALP is more strongly associated with biliary excretion defects in pancreaticobiliary disease.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "low", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "AST is not a glycoprotein but reflects hepatocyte injury affecting glycoprotein metabolism.", "mechanism": "AST levels mildly correlate with suboptimal MRI imaging in CLD.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "low", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "ALT is not a glycoprotein but reflects hepatocyte injury affecting glycoprotein metabolism.", "mechanism": "ALT levels mildly correlate with suboptimal MRI imaging in CLD.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10659682" }, { "confidence": "medium", "disease": "Allergic reaction/hypersensitivity", "glycan_involvement": "IL-12 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Reduced IL-12 expression may facilitate hypersensitivity reactions by failing to inhibit IL-18-driven allergy.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "high", "disease": "Allergic reaction/hypersensitivity", "glycan_involvement": "IL-18 is glycosylated; glycosylation modulates activity and secretion.", "mechanism": "Elevated IL-18 promotes allergic responses via mast cell and basophil activation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "IFN-\u03b3 is glycosylated; glycosylation affects receptor binding.", "mechanism": "Increased IFN-\u03b3 indicates pro-inflammatory state and immune activation.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates IL-18 secretion and function.", "mechanism": "IL-18 overproduction is linked to asthma pathogenesis via Th2/Th1 imbalance.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Dermatitis", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "IL-18 stimulates allergic skin inflammation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Rhinitis", "glycan_involvement": "Glycosylation affects IL-18 bioactivity.", "mechanism": "IL-18 promotes allergic rhinitis via leukocyte activation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Eosinophilic disorders", "glycan_involvement": "Glycosylation modulates secretion and immune recognition.", "mechanism": "IL-18 stimulates eosinophil proliferation and activation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "high", "disease": "Infection", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "IL-12 activates NK and T cells for pathogen clearance.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects IFN-\u03b3 stability and function.", "mechanism": "IFN-\u03b3 induces hepatocyte apoptosis and inhibits cell cycle during liver disease.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC10668812" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation required for secretion and anti-inflammatory function.", "mechanism": "IL-10 inhibits pro-inflammatory cytokines, protecting against autoimmunity.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC10668812" }, { "confidence": "high", "disease": "Congenital myasthenic syndrome type 4C (CMS4C)", "glycan_involvement": "N-glycosylation is required for proper folding and surface expression of CHRNE; loss of protein disrupts glycosylation-dependent assembly.", "mechanism": "Homozygous duplication in CHRNE leads to frameshift and premature termination, causing loss of function of the acetylcholine receptor at the neuromuscular junction.", "protein": "Cholinergic receptor nicotinic epsilon subunit (CHRNE)", "relationship_type": "causal", "source_pmcid": "PMC10668953" }, { "confidence": "high", "disease": "Congenital myasthenic syndrome type 4A (CMS4A)", "glycan_involvement": "N-glycosylation is essential for receptor assembly and function.", "mechanism": "Mutations in CHRNE alter acetylcholine receptor function, leading to impaired neuromuscular transmission.", "protein": "Cholinergic receptor nicotinic epsilon subunit (CHRNE)", "relationship_type": "causal", "source_pmcid": "PMC10668953" }, { "confidence": "medium", "disease": "Congenital myasthenic syndrome type 4B (CMS4B)", "glycan_involvement": "N-glycosylation affects receptor stability and trafficking.", "mechanism": "CHRNE mutations cause receptor deficiency or abnormal channel kinetics.", "protein": "Cholinergic receptor nicotinic epsilon subunit (CHRNE)", "relationship_type": "causal", "source_pmcid": "PMC10668953" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG affects antigenicity and immune recognition.", "mechanism": "MOG is a target antigen in MS and EAE; immune response against MOG induces demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may influence antibody binding and immune recognition.", "mechanism": "Antibodies from MS patients cross-react with GlialCAM and EBV EBNA-1, suggesting molecular mimicry.", "protein": "Glial cell adhesion molecule (GlialCAM)", "protein_enriched": { "function": "May be a negative regulator of NF-kappa-B and p53-mediated gene transcription", "gene_name": "STK40", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N2I9" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation status may modulate immunogenicity.", "mechanism": "EBV antibodies may cross-react with MBP, triggering autoimmune demyelination.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may affect antigen processing.", "mechanism": "EBV infection induces alpha B-crystallin in B cells, activating T cells that recognize it in MS lesions.", "protein": "Alpha B-crystallin", "protein_enriched": { "function": "May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial", "gene_name": "CRYAB", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02511" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10668955" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation affects secretion and activity of MMP-9.", "mechanism": "MMP-9 mediates blood\u2013brain barrier disruption; minocycline and doxycycline inhibit MMP-9, reducing MS activity.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may influence GFAP stability and detection.", "mechanism": "Serum GFAP is elevated in MS; minocycline and HCQ reduce GFAP, reflecting decreased astrocyte activation.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may affect NfL clearance and immunoassay detection.", "mechanism": "Serum NfL reflects neuroaxonal damage; minocycline and HCQ modulate NfL levels.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation is important for NGF secretion and function.", "mechanism": "Higher NGF levels are associated with MS relapse recovery; minocycline upregulates NGF.", "protein": "Nerve growth factor (NGF)", "protein_enriched": { "function": "Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1 and NGFR rece", "gene_name": "NGF", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01138" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation affects BDNF stability and receptor interaction.", "mechanism": "BDNF is lower in MS; minocycline increases BDNF, supporting neuroprotection.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Viral glycoprotein glycosylation may affect immune cross-reactivity.", "mechanism": "Antibodies to EBNA-1 cross-react with CNS glycoproteins (e.g., GlialCAM), supporting molecular mimicry in MS.", "protein": "Epstein\u2013Barr virus nuclear antigen 1 (EBNA-1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10668955" }, { "confidence": "high", "disease": "Skin cancer", "glycan_involvement": "Not discussed", "mechanism": "UVB-induced reactivation of LINE-1 leads to genomic instability and DNA damage, promoting carcinogenesis.", "protein": "LINE-1 ORF1p", "protein_enriched": { "function": "Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially m", "gene_name": "L1RE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UN81" }, "relationship_type": "causal", "source_pmcid": "PMC10669206" }, { "confidence": "high", "disease": "Photoaging", "glycan_involvement": "Not discussed", "mechanism": "LINE-1 reactivation by UVB triggers DNA damage and cellular senescence, contributing to photoaging.", "protein": "LINE-1 ORF1p", "protein_enriched": { "function": "Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially m", "gene_name": "L1RE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UN81" }, "relationship_type": "causal", "source_pmcid": "PMC10669206" }, { "confidence": "high", "disease": "Cellular senescence", "glycan_involvement": "Not discussed", "mechanism": "LINE-1 activation increases senescence markers (IFN-\u03b2, IL-6, IL-8, MMP1, MMP3) in keratinocytes.", "protein": "LINE-1 ORF1p", "protein_enriched": { "function": "Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially m", "gene_name": "L1RE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UN81" }, "relationship_type": "causal", "source_pmcid": "PMC10669206" }, { "confidence": "high", "disease": "Skin cancer", "glycan_involvement": "Not discussed", "mechanism": "\u03b3H2AX upregulation marks UVB-induced DNA double-strand breaks, a precursor to carcinogenesis.", "protein": "\u03b3H2AX", "protein_enriched": { "function": "Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DN", "gene_name": "H2AX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P16104" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "Not discussed", "mechanism": "Upregulated as part of the senescence-associated secretory phenotype after UVB and LINE-1 activation.", "protein": "IFN-\u03b2", "protein_enriched": { "function": "Type I interferon cytokine that plays a key role in the innate immune response to infection, developing tumors and other inflammatory stimuli (PubMed:10049744, PubMed:10556041, PubMed:6157094, PubMed:", "gene_name": "IFNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G17689DH", "G22310AV" ], "uniprot_id": "P01574" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "Not discussed", "mechanism": "Upregulated in keratinocytes undergoing UVB-induced senescence.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "Not discussed", "mechanism": "Upregulated in senescent keratinocytes after UVB and LINE-1 activation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Photoaging", "glycan_involvement": "Not discussed", "mechanism": "MMP1 upregulation is associated with extracellular matrix degradation in photoaged skin.", "protein": "MMP1", "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Photoaging", "glycan_involvement": "Not discussed", "mechanism": "MMP3 upregulation contributes to matrix remodeling in photoaging.", "protein": "MMP3", "protein_enriched": { "function": "Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activa", "gene_name": "MMP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P08254" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669206" }, { "confidence": "medium", "disease": "Autoimmune diseases (e.g., lupus erythematosus)", "glycan_involvement": "Not discussed", "mechanism": "UVB-induced LINE-1 expression may trigger autoantibody production via aberrant antigen presentation.", "protein": "LINE-1 ORF1p", "protein_enriched": { "function": "Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially m", "gene_name": "L1RE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UN81" }, "relationship_type": "causal", "source_pmcid": "PMC10669206" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation affects function and interactions.", "mechanism": "Regulates coagulation cascade and platelet activation; increased in aged platelets.", "protein": "Beta-2-glycoprotein 1 (ApoH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "N-glycosylation modulates activity.", "mechanism": "Platelet ApoH expression associated with early-stage stroke.", "protein": "Beta-2-glycoprotein 1 (ApoH)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation may influence immune interactions.", "mechanism": "Involved in platelet damage and hemostasis inhibition, affecting severity.", "protein": "Beta-2-glycoprotein 1 (ApoH)", "relationship_type": "causal", "source_pmcid": "PMC10669211" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "12\u201320 N-glycosylation sites; glycoforms modulate platelet/neutrophil function.", "mechanism": "Regulates platelet shape/activity, stabilizes plasminogen activator inhibitor, induces thrombosis.", "protein": "Alpha-1-acid glycoprotein 2 (Orm2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycoform pattern changes in acute/chronic inflammation.", "mechanism": "Increased AGP-1/Orm2 levels correlated with stroke incidence.", "protein": "Alpha-1-acid glycoprotein 2 (Orm2)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "Gray platelet syndrome (GPS)", "glycan_involvement": "N-glycosylation may affect granule formation.", "mechanism": "Orm2 expression decreased in GPS platelets.", "protein": "Alpha-1-acid glycoprotein 2 (Orm2)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation pattern may influence immune response.", "mechanism": "Acute phase glycoprotein increased in severe COVID-19.", "protein": "Alpha-1-acid glycoprotein 2 (Orm2)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Not glycosylated; indirect via vesicle trafficking of glycoproteins.", "mechanism": "Increased in aged platelets; regulates membrane trafficking and platelet function.", "protein": "Ras-related protein Rab11a", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB11A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62491" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669211" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "Elevated plasma CD62p predicts platelet activation and aggregation.", "protein": "CD62p (P-selectin)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "medium", "disease": "Carotid plaque", "glycan_involvement": "Glycoform diversity affects vascular inflammation.", "mechanism": "Increased AGP-1/Orm2 levels correlated with carotid plaque incidence.", "protein": "Alpha-1-acid glycoprotein 2 (Orm2)", "relationship_type": "biomarker", "source_pmcid": "PMC10669211" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation affects its interaction with the viral spike protein.", "mechanism": "ACE2 acts as the main entry receptor for SARS-CoV-2, facilitating viral entry into host cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike protein mediates viral attachment and fusion with host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of CD147 may influence viral binding.", "mechanism": "Alternative receptor for SARS-CoV-2 entry into host cells.", "protein": "CD147 (EMMPRIN)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NRP1 is glycosylated; glycan structures may modulate interaction.", "mechanism": "Facilitates SARS-CoV-2 entry as an alternative receptor.", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "DPP4 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Potential alternative entry receptor for SARS-CoV-2.", "protein": "DPP4", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Lectin-glycan interactions are central to viral attachment.", "mechanism": "May mediate SARS-CoV-2 entry via glycan recognition.", "protein": "C-type lectins (e.g., CD209/L, CLEC4G)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation modulates immune recognition and cytokine response.", "mechanism": "Spike protein triggers immune activation leading to hyperinflammation.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "Glycosylation affects spike stability and host interaction.", "mechanism": "Spike-mediated viral entry leads to lung injury and ARDS.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield impacts vaccine and antibody efficacy.", "mechanism": "Target of neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669259" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation may affect ACE2 distribution and viral tropism.", "mechanism": "ACE2 expression in multiple organs mediates viral entry and tissue damage.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10669259" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "XO is a glycoprotein; glycosylation may affect stability and activity.", "mechanism": "XO catalyzes uric acid production, promoting hepatic steatosis via ROS and lipogenesis.", "protein": "Xanthine oxidase (XO)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669273" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "NLRP3 is glycosylated; glycosylation may regulate inflammasome assembly.", "mechanism": "Uric acid activates NLRP3 inflammasome, increasing inflammation and fat accumulation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "XO glycosylation may modulate enzyme secretion and activity.", "mechanism": "XO increases uric acid production, leading to hyperuricemia.", "protein": "Xanthine oxidase (XO)", "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect NLRP3 activation threshold.", "mechanism": "NLRP3 activation by uric acid impairs insulin signaling.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is glycosylated; glycosylation may affect serum stability.", "mechanism": "ALT elevation indicates hepatocyte injury in MASLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10669273" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST glycosylation may influence serum half-life.", "mechanism": "AST elevation reflects liver injury in MASLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC10669273" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation of inflammasome components may regulate assembly.", "mechanism": "NLRP3 inflammasome activation drives progression from steatosis to steatohepatitis.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "XO glycosylation may affect ROS generation.", "mechanism": "XO-derived ROS contribute to liver fibrosis.", "protein": "Xanthine oxidase (XO)", "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may modulate NLRP3 stability.", "mechanism": "Chronic NLRP3 activation promotes carcinogenesis via inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10669273" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "XO glycosylation may influence drug response.", "mechanism": "XO inhibition (allopurinol/febuxostat) reduces hepatic steatosis.", "protein": "Xanthine oxidase (XO)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669273" }, { "confidence": "high", "disease": "Gastric cancer (GC)", "glycan_involvement": "Highly glycosylated; glycosylation mediates ECM interactions and lipid retention.", "mechanism": "BGN expression correlates with amino acid and lipid metabolism, and is associated with poor prognosis and immune evasion.", "protein": "BGN", "protein_enriched": { "function": "May be involved in collagen fiber assembly", "gene_name": "BGN", "glycan_count": 276, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02030ZB", "G02315DX", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G05049YU", "G05933EN", "G05962QB", "G06356OH", "G07246CJ", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G09197ZW", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G11911BT", "G13131HA", "G14972EH", "G14994KB", "G16125XL", "G16175ZV", "G17208MA", "G19379ID", "G20312EM", "G20425TQ", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23505EP", "G23719VF", "G23863VK", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G29880MM", "G30769VJ", "G30970QQ", "G31596VW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37509XX", "G37995HC", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41126SR", "G41882MT", "G42124LM", "G43223CG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G46503DX", "G46524LG", "G46687AB", "G46691LC", "G46902YN", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G49642SA", "G49874UX", "G49906RN", "G50045TK", "G50073PQ", "G50757KG", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G58087IP", "G58802FE", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G60923RB", "G61256FT", "G62595EF", "G62765YT", "G63381RX", "G63980BQ", "G64394MX", "G64409MC", "G64527OM", "G65019XG", "G65092SV", "G65184UU", "G66163OV", "G66621EA", "G66760KM", "G68490OW", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71463BG", "G72398FA", "G72667IM", "G72735IY", "G72747WU", "G72797UR", "G73430PD", "G73968GN", "G74430RZ", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G78787DI", "G78790NZ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82119TF", "G82592ZH", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G84862VB", "G85282JO", "G86182NS", "G86234IN", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88891KO", "G89045VA", "G89098OM", "G90382BL", "G90575OW", "G90659AW", "G91636VS", "G92081HT", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G93683YO", "G93718GY", "G94470IW", "G95177YH", "G96577RX", "G98129XB", "G00273SJ", "G01650EU", "G02528FI", "G04672QB", "G04854VP", "G06247RL", "G07810QS", "G11115RO", "G11870QZ", "G12313PD", "G12341GU", "G13191RB", "G13910DJ", "G15127JD", "G15169WU", "G15664MX", "G18647XP", "G24528MX", "G26403SG", "G28622IK", "G28681TP", "G30740WO", "G31852PQ", "G31916IQ", "G31986NC", "G32788FZ", "G37399XV", "G37412TK", "G37692EO", "G37818NZ", "G39446WN", "G39471UU", "G39595FH", "G40206WX", "G41840AI", "G43669FQ", "G43734MM", "G43769HG", "G45504EY", "G47702MW", "G48414YA", "G49018RC", "G49955PK", "G51640FO", "G52358QA", "G54010QB", "G54612UD", "G56307ZW", "G57776ZU", "G63041LO", "G66766XF", "G67164EE", "G72197KC", "G72787SB", "G72790NZ", "G75006KF", "G75418YA", "G77582RK", "G78502KD", "G78649WQ", "G82443XX", "G82463GQ", "G85554PZ", "G85677PP", "G85740DB", "G90734RJ", "G91473PK", "G92050GC", "G94665LC", "G95865ZB", "G95977AE", "G96430BV", "G98611JV", "G99668VU", "G43417UB", "G49108TO" ], "uniprot_id": "P21810" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669360" }, { "confidence": "high", "disease": "Gastric cancer (GC)", "glycan_involvement": "O-GlcNAcylation of target proteins enhances stability and oncogenic signaling.", "mechanism": "OGT catalyzes O-GlcNAcylation, promoting GC progression and correlating with advanced stage and nodal metastases.", "protein": "OGT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669360" }, { "confidence": "medium", "disease": "Gastric cancer (GC)", "glycan_involvement": "Glycosylation may affect tight junction integrity and cell adhesion.", "mechanism": "CLDN9 expression is linked to high invasiveness and mortality in GC.", "protein": "CLDN9", "protein_enriched": { "function": "Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA", "gene_name": "BCLAF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G92050GC" ], "uniprot_id": "Q9NYF8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669360" }, { "confidence": "medium", "disease": "Gastric cancer (GC)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and function.", "mechanism": "SERPINE1 is part of the HGLRG signature predicting poor prognosis.", "protein": "SERPINE1", "relationship_type": "biomarker", "source_pmcid": "PMC10669360" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation (sulfate/carboxyl groups) mediates binding to lipoproteins.", "mechanism": "BGN exacerbates atherosclerosis via lipid retention and interaction with lipoproteins.", "protein": "BGN", "protein_enriched": { "function": "May be involved in collagen fiber assembly", "gene_name": "BGN", "glycan_count": 276, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02030ZB", "G02315DX", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G05049YU", "G05933EN", "G05962QB", "G06356OH", "G07246CJ", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G09197ZW", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G11911BT", "G13131HA", "G14972EH", "G14994KB", "G16125XL", "G16175ZV", "G17208MA", "G19379ID", "G20312EM", "G20425TQ", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23505EP", "G23719VF", "G23863VK", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G29880MM", "G30769VJ", "G30970QQ", "G31596VW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37509XX", "G37995HC", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41126SR", "G41882MT", "G42124LM", "G43223CG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G46503DX", "G46524LG", "G46687AB", "G46691LC", "G46902YN", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G49642SA", "G49874UX", "G49906RN", "G50045TK", "G50073PQ", "G50757KG", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G58087IP", "G58802FE", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G60923RB", "G61256FT", "G62595EF", "G62765YT", "G63381RX", "G63980BQ", "G64394MX", "G64409MC", "G64527OM", "G65019XG", "G65092SV", "G65184UU", "G66163OV", "G66621EA", "G66760KM", "G68490OW", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71463BG", "G72398FA", "G72667IM", "G72735IY", "G72747WU", "G72797UR", "G73430PD", "G73968GN", "G74430RZ", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G78787DI", "G78790NZ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82119TF", "G82592ZH", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G84862VB", "G85282JO", "G86182NS", "G86234IN", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88891KO", "G89045VA", "G89098OM", "G90382BL", "G90575OW", "G90659AW", "G91636VS", "G92081HT", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G93683YO", "G93718GY", "G94470IW", "G95177YH", "G96577RX", "G98129XB", "G00273SJ", "G01650EU", "G02528FI", "G04672QB", "G04854VP", "G06247RL", "G07810QS", "G11115RO", "G11870QZ", "G12313PD", "G12341GU", "G13191RB", "G13910DJ", "G15127JD", "G15169WU", "G15664MX", "G18647XP", "G24528MX", "G26403SG", "G28622IK", "G28681TP", "G30740WO", "G31852PQ", "G31916IQ", "G31986NC", "G32788FZ", "G37399XV", "G37412TK", "G37692EO", "G37818NZ", "G39446WN", "G39471UU", "G39595FH", "G40206WX", "G41840AI", "G43669FQ", "G43734MM", "G43769HG", 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"G50757KG", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G58087IP", "G58802FE", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G60923RB", "G61256FT", "G62595EF", "G62765YT", "G63381RX", "G63980BQ", "G64394MX", "G64409MC", "G64527OM", "G65019XG", "G65092SV", "G65184UU", "G66163OV", "G66621EA", "G66760KM", "G68490OW", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71463BG", "G72398FA", "G72667IM", "G72735IY", "G72747WU", "G72797UR", "G73430PD", "G73968GN", "G74430RZ", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G78787DI", "G78790NZ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82119TF", "G82592ZH", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G84862VB", "G85282JO", "G86182NS", "G86234IN", "G86795LJ", "G86880BF", 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"gene_name": "BGN", "glycan_count": 276, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02030ZB", "G02315DX", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G04657PL", "G05049YU", "G05933EN", "G05962QB", "G06356OH", "G07246CJ", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G09197ZW", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G11911BT", "G13131HA", "G14972EH", "G14994KB", "G16125XL", "G16175ZV", "G17208MA", "G19379ID", "G20312EM", "G20425TQ", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23505EP", "G23719VF", "G23863VK", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G29880MM", "G30769VJ", "G30970QQ", "G31596VW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37509XX", "G37995HC", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41126SR", "G41882MT", "G42124LM", "G43223CG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G46503DX", "G46524LG", "G46687AB", "G46691LC", "G46902YN", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G49642SA", "G49874UX", "G49906RN", "G50045TK", "G50073PQ", "G50757KG", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G58087IP", "G58802FE", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G60923RB", "G61256FT", "G62595EF", "G62765YT", "G63381RX", "G63980BQ", "G64394MX", "G64409MC", "G64527OM", "G65019XG", "G65092SV", "G65184UU", "G66163OV", "G66621EA", "G66760KM", "G68490OW", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71463BG", "G72398FA", "G72667IM", "G72735IY", "G72747WU", "G72797UR", "G73430PD", "G73968GN", "G74430RZ", "G75983OB", "G76295SF", "G77547TA", "G77669RF", "G78787DI", "G78790NZ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80479JV", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82119TF", "G82592ZH", "G82830MN", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G84862VB", "G85282JO", "G86182NS", "G86234IN", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88891KO", "G89045VA", "G89098OM", "G90382BL", "G90575OW", "G90659AW", "G91636VS", "G92081HT", "G92135MA", "G92275SC", "G92406TI", "G92551JA", "G93683YO", "G93718GY", "G94470IW", "G95177YH", "G96577RX", "G98129XB", "G00273SJ", "G01650EU", "G02528FI", "G04672QB", "G04854VP", "G06247RL", "G07810QS", "G11115RO", "G11870QZ", "G12313PD", "G12341GU", "G13191RB", "G13910DJ", "G15127JD", "G15169WU", "G15664MX", "G18647XP", "G24528MX", "G26403SG", "G28622IK", "G28681TP", "G30740WO", "G31852PQ", "G31916IQ", "G31986NC", "G32788FZ", "G37399XV", "G37412TK", "G37692EO", "G37818NZ", "G39446WN", "G39471UU", "G39595FH", "G40206WX", "G41840AI", "G43669FQ", "G43734MM", "G43769HG", "G45504EY", "G47702MW", "G48414YA", "G49018RC", "G49955PK", "G51640FO", "G52358QA", "G54010QB", "G54612UD", "G56307ZW", "G57776ZU", "G63041LO", "G66766XF", "G67164EE", "G72197KC", "G72787SB", "G72790NZ", "G75006KF", "G75418YA", "G77582RK", "G78502KD", "G78649WQ", "G82443XX", "G82463GQ", "G85554PZ", "G85677PP", "G85740DB", "G90734RJ", "G91473PK", "G92050GC", "G94665LC", "G95865ZB", "G95977AE", "G96430BV", "G98611JV", "G99668VU", "G43417UB", "G49108TO" ], "uniprot_id": "P21810" }, "relationship_type": "causal", "source_pmcid": "PMC10669360" }, { "confidence": "medium", "disease": "Metastasis in GC", "glycan_involvement": "O-GlcNAcylation at specific sites increases metastatic potential.", "mechanism": "O-GlcNAcylation by OGT enhances stability of metastasis-promoting proteins.", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC10669360" }, { "confidence": "high", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "ApoA is a heavily glycosylated protein; glycosylation affects its size, plasma levels, and function.", "mechanism": "Elevated LpA (containing ApoA) levels are associated with increased IA risk and familial clustering; ApoA mediates lipid deposition and inflammation in vessel wall.", "protein": "Apolipoprotein(a) (ApoA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "APOE is glycosylated; glycosylation may modulate receptor binding and lipid transport.", "mechanism": "Certain APOE genotypes (E2/E2, E2/E3) are more frequent in IA patients, suggesting increased susceptibility via altered lipid metabolism.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669412" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation of ApoA influences its interaction with vessel wall and clearance.", "mechanism": "ApoA in LpA promotes atherogenesis by binding to damaged endothelium and carrying oxidized phospholipids, driving inflammation.", "protein": "Apolipoprotein(a) (ApoA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Calcific aortic stenosis", "glycan_involvement": "Glycosylation affects ApoA isoform size and plasma concentration.", "mechanism": "Elevated LpA (ApoA) levels are independently linked to increased risk of aortic valve calcification.", "protein": "Apolipoprotein(a) (ApoA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "APOA1 is glycosylated; glycosylation may affect HDL formation and function.", "mechanism": "APOA1 gene variants (A/G genotype, A allele) are associated with increased IA incidence, possibly via HDL metabolism.", "protein": "Apolipoprotein A1 (APOA1)", "protein_enriched": { "function": "Glycinin is the major seed storage protein of soybean (PubMed:2485233). Glycinin basic peptides (GBPs), and, to a lower extent, glycinin exhibit antibacterial activity against Gram-negative and Gram-p", "gene_name": "GY1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04776" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "LDLR is N-glycosylated; glycosylation is essential for receptor function and trafficking.", "mechanism": "Increased LDLR expression in IA patients suggests altered lipid uptake in vessel wall, contributing to IA pathogenesis.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "ABCA1 is glycosylated; glycosylation affects stability and function.", "mechanism": "Altered ABCA1 expression in IA wall affects lipid efflux and accumulation, contributing to vessel wall degeneration.", "protein": "ATP-binding cassette transporter A1 (ABCA1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10669412" }, { "confidence": "low", "disease": "Aneurysmal subarachnoid hemorrhage (aSAH)", "glycan_involvement": "Glycosylation may modulate APOE's neuroprotective and lipid transport functions.", "mechanism": "APOE \u03b54 allele may be associated with poor prognosis after aSAH, possibly via effects on lipid metabolism and inflammation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Intracranial aneurysm (IA)", "glycan_involvement": "Contains glycosylated ApoA; glycosylation affects LpA structure and function.", "mechanism": "LpA concentration in IA sac correlates with wall degeneration and rupture risk.", "protein": "Lipoprotein(a) (LpA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10669412" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Both are glycoproteins; glycosylation affects their plasma half-life and interactions.", "mechanism": "ApoA structural similarity to plasminogen may competitively inhibit fibrinolysis, promoting thrombosis in ASCVD.", "protein": "Plasminogen", "relationship_type": "protective/competitive", "source_pmcid": "PMC10669412" }, { "confidence": "high", "disease": "Cardiovascular Events", "glycan_involvement": "sEng is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Low plasma sEng levels are independently associated with increased risk of cardiovascular events in patients undergoing coronary angiography.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation is essential for sEng structure and function.", "mechanism": "Lower sEng levels are found in patients with CAD compared to those without CAD.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "high", "disease": "Cardiovascular Events in CAD patients", "glycan_involvement": "Glycosylation affects sEng secretion and function.", "mechanism": "Low sEng levels predict further cardiovascular events in patients with established CAD.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Endoglin is a glycoprotein; glycosylation is required for cell surface expression.", "mechanism": "Endoglin expression is upregulated in atherosclerotic plaques and may contribute to plaque stabilization.", "protein": "Endoglin (CD105)", "relationship_type": "protective", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is necessary for receptor function.", "mechanism": "Endoglin regulates TGF-\u03b2 signaling, which inhibits vascular cell proliferation and inflammation.", "protein": "Endoglin (CD105)", "relationship_type": "causal", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is required for sEng's stability and interaction with TGF-\u03b2.", "mechanism": "sEng acts as a decoy receptor, antagonizing TGF-\u03b2 signaling and potentially promoting atherosclerosis.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "causal", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation affects sEng's circulatory half-life.", "mechanism": "Lower sEng levels are associated with increased cardiovascular mortality post-MI.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation is necessary for sEng secretion.", "mechanism": "Lower sEng levels are observed in patients with stroke and decrease further after the event.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Glycosylation is required for sEng's function.", "mechanism": "sEng levels are higher in patients with elevated LV end-diastolic pressure, but not in those with normal pressure.", "protein": "Soluble Endoglin (sEng)", "relationship_type": "biomarker", "source_pmcid": "PMC10669441" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is essential for endoglin's cell surface localization and function.", "mechanism": "High endoglin expression in plaques is associated with increased collagen and smooth muscle cells, suggesting plaque stabilization.", "protein": "Endoglin (CD105)", "relationship_type": "protective", "source_pmcid": "PMC10669441" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "FNDC5 is a glycoprotein; glycosylation may affect its cleavage and irisin release.", "mechanism": "Exercise-induced FNDC5/irisin upregulates BDNF in hippocampus, improving memory and synaptic plasticity.", "protein": "FNDC5", "relationship_type": "protective", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation affects processing and A\u03b2 production.", "mechanism": "APP is cleaved to produce amyloid-\u03b2, forming plaques central to AD pathology.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "BDNF is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "BDNF promotes neuronal survival, synaptic plasticity; levels are reduced in AD and correlate with cognitive decline.", "protein": "BDNF", "relationship_type": "protective/biomarker", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation may modulate aggregation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, causing synaptic loss and cognitive impairment.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Irisin is a glycoprotein fragment; glycosylation may affect stability.", "mechanism": "Irisin (from FNDC5) increases BDNF, supporting learning and memory; reduced in AD.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10669442" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "ADAM10 is N-glycosylated; glycosylation affects trafficking and activity.", "mechanism": "ADAM10 (\u03b1-secretase) promotes non-amyloidogenic APP processing, reducing A\u03b2 production.", "protein": "ADAM10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "BACE1 is N-glycosylated; glycosylation is critical for folding and function.", "mechanism": "BACE1 (\u03b2-secretase) cleaves APP to generate A\u03b2; exercise/BDNF reduces BACE1, lowering A\u03b2.", "protein": "BACE1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10669442" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Osteocalcin is a glycoprotein; glycosylation may affect secretion.", "mechanism": "Exercise-induced osteocalcin increases BDNF via Gpr158, improving cognition and reducing A\u03b2.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "protective", "source_pmcid": "PMC10669442" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "AEP is N-glycosylated; glycosylation may affect activity.", "mechanism": "\u03b4-secretase cleaves APP, enhancing A\u03b2 production; BDNF inhibits \u03b4-secretase activity.", "protein": "\u03b4-secretase (AEP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10669442" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Gpr158 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Gpr158 mediates osteocalcin-induced BDNF upregulation, supporting memory.", "protein": "Gpr158", "protein_enriched": { "function": "Receptor activated by multiple ligands, including osteocalcin (BGLAP), basic amino acids, and various cations (PubMed:15576628). Activated by amino acids with a preference for basic amino acids such a", "gene_name": "GPRC6A", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q5T6X5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669442" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP processing and amyloidogenic cleavage.", "mechanism": "Mutations lead to amyloid-beta plaque accumulation and neurodegeneration.", "protein": "APP (Amyloid precursor protein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10669457" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor activation.", "mechanism": "Overexpression and activation drive tumor proliferation and survival.", "protein": "EGFR (Epidermal growth factor receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect chaperone function and client protein interactions.", "mechanism": "Chaperone stabilizes tau and amyloid-beta aggregates.", "protein": "HSP90AA1 (Heat shock protein 90 alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Neurocognitive impairment", "glycan_involvement": "Ubiquitin itself is not glycosylated, but targets glycoproteins for degradation.", "mechanism": "Accumulation of ubiquitinated proteins indicates proteasome dysfunction.", "protein": "UBC (Polyubiquitin-C)", "relationship_type": "biomarker", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; targets glycoproteins for degradation.", "mechanism": "Mutant UBB accumulates in neurofibrillary tangles.", "protein": "UBB (Polyubiquitin-B)", "protein_enriched": { "function": "Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a pol", "gene_name": "UBC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P0CG48" }, "relationship_type": "causal", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Proteasome subunits can be glycosylated, affecting assembly and function.", "mechanism": "Altered proteasomal activity leads to protein aggregation.", "protein": "PSMA3 (Proteasome subunit alpha type-3)", "protein_enriched": { "function": "Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with dif", "gene_name": "PSMA3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G05962QB", "G49108TO" ], "uniprot_id": "P25788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may regulate nuclear localization and activity.", "mechanism": "Dysregulation impairs synaptic plasticity and memory.", "protein": "CREBBP (CREB-binding protein)", "protein_enriched": { "function": "Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respecti", "gene_name": "CREBBP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q92793" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669457" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may modulate transcriptional coactivator function.", "mechanism": "Hyperacetylation of tau promotes tauopathy.", "protein": "EP300 (Histone acetyltransferase p300)", "protein_enriched": { "function": "Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:8945521). Acetylates all four core histones in nucleosomes (PubM", "gene_name": "EP300", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q09472" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669457" }, { "confidence": "high", "disease": "Parkinson's disease with dementia", "glycan_involvement": "O-GlcNAc modification reduces aggregation propensity.", "mechanism": "Aggregation leads to Lewy body formation and neuronal loss.", "protein": "SNCA (Alpha-synuclein)", "relationship_type": "causal", "source_pmcid": "PMC10669457" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects lipid binding and amyloid clearance.", "mechanism": "APOE4 allele increases amyloid deposition and risk.", "protein": "APOE (Apolipoprotein E)", "relationship_type": "causal", "source_pmcid": "PMC10669457" }, { "confidence": "high", "disease": "Proliferative Diabetic Retinopathy (PDR)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "VEGF promotes pathological angiogenesis and vascular permeability in the retina under hypoxic conditions.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Diabetic Macular Edema", "glycan_involvement": "Glycosylation affects VEGF's bioactivity and receptor binding.", "mechanism": "VEGF increases vascular permeability, leading to fluid accumulation in the macula.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "PGF is a glycoprotein; glycosylation may affect secretion.", "mechanism": "PGF binds VEGFR1, promoting inflammatory angiogenesis; levels increase in NPDR after anti-VEGF therapy.", "protein": "Placenta Growth Factor (PGF)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "ET-1 is derived from a glycoprotein precursor; glycosylation affects processing.", "mechanism": "ET-1 induces vasoconstriction, endothelial dysfunction, and retinal ischemia; levels correlate with DR severity.", "protein": "Endothelin-1 (ET-1)", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "EDN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P05305" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "AGEs are glycation-modified proteins; glycation alters protein function and structure.", "mechanism": "AGEs accumulate in retinal tissues, activate RAGE, induce oxidative stress, inflammation, and neurovascular damage.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669459" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "RAGE is a glycoprotein; glycosylation may affect ligand binding and signaling.", "mechanism": "RAGE mediates AGEs-induced proinflammatory and proangiogenic signaling in retinal cells.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "OPN is a phosphoglycoprotein; glycosylation modulates function.", "mechanism": "OPN promotes basement membrane thickening and vascular hyperpermeability in diabetic retina.", "protein": "Osteopontin (OPN/SPP1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Proliferative Diabetic Retinopathy (PDR)", "glycan_involvement": "VEGFR2 is a glycoprotein; N-glycosylation is critical for receptor function.", "mechanism": "VEGFR2 mediates VEGF-driven angiogenesis; anti-VEGFR2 therapies reduce neovascularization.", "protein": "VEGF Receptor 2 (VEGFR2/KDR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Neuropilin-1 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "Neuropilin-1 enhances VEGF-VEGFR2 signaling, promoting angiogenesis.", "protein": "Neuropilin-1", "relationship_type": "modulator/therapeutic_target", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Diabetic Microangiopathy", "glycan_involvement": "Protein glycation is the defining modification.", "mechanism": "AGEs contribute to microvascular damage in diabetes, including retinopathy, nephropathy, and neuropathy.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10669459" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "HBsAg is heavily glycosylated, affecting immune recognition and viral infectivity.", "mechanism": "HBsAg is used to diagnose HBV infection and monitor reactivation risk during chemotherapy.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Hepatitis C virus infection", "glycan_involvement": "E2 glycosylation modulates immune evasion and receptor binding.", "mechanism": "E2 glycoprotein is a target for anti-HCV antibody detection and viral entry.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "AST is glycosylated, which may affect its serum stability.", "mechanism": "AST levels are used in APRI and FIB-4 scores to assess liver fibrosis and cirrhosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Acute hepatitis exacerbation", "glycan_involvement": "ALT is glycosylated, influencing its secretion and activity.", "mechanism": "ALT elevation (>10x normal) signals acute liver injury during chemoradiotherapy.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation and are altered in cirrhosis.", "mechanism": "Platelet count is used in APRI and FIB-4 scores to assess liver fibrosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "medium", "disease": "Hepatitis B virus infection", "glycan_involvement": "Polymerase glycosylation may affect drug binding and viral replication.", "mechanism": "Targeted by antiviral drugs (entecavir, lamivudine, adefovir) to suppress HBV replication.", "protein": "HBV DNA polymerase", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19795" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Hepatitis C virus infection", "glycan_involvement": "Immunoglobulin glycosylation affects antibody function and clearance.", "mechanism": "Detection of anti-HCV antibodies confirms HCV infection and monitors exacerbation.", "protein": "Anti-HCV antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation does not impact HNC prognosis in this context.", "mechanism": "HBsAg status does not affect overall survival in HNC patients receiving CCRT.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation does not impact HNC prognosis in this context.", "mechanism": "HCV infection status does not affect overall survival in HNC patients receiving CCRT.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation may affect AST serum levels and prognostic accuracy.", "mechanism": "AST-based scores (APRI, FIB-4) are independent predictors of survival in HNC patients on CCRT.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10669880" }, { "confidence": "high", "disease": "Mercuric chloride-induced hepatorenal toxicity", "glycan_involvement": "Albumin is a glycoprotein; glycosylation may affect nanoparticle stability and tissue targeting.", "mechanism": "Albumin nanoparticles encapsulating CoQ10 enhance delivery and antioxidant protection, reducing oxidative stress, inflammation, and apoptosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC10669886" }, { "confidence": "high", "disease": "Kidney injury", "glycan_involvement": "KIM-1 is a glycoprotein; glycosylation is essential for its cell surface expression and function.", "mechanism": "Serum KIM-1 levels increase with HgCl2-induced renal injury; reduced by CoQ10/albumin NP treatment.", "protein": "Kidney injury molecule-1 (KIM-1)", "protein_enriched": { "function": "Stimulates the release of tumor necrosis factor alpha and IL-1-beta from the monocytic cell line THP-1", "gene_name": "IL17B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UHF5" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669886" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects secretion and receptor binding.", "mechanism": "TNF-\u03b1 is upregulated in HgCl2 toxicity, driving inflammation; reduced by CoQ10/albumin NP treatment.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10669886" }, { "confidence": "high", "disease": "Renal inflammation", "glycan_involvement": "IL-1\u03b2 glycosylation modulates its stability and activity.", "mechanism": "IL-1\u03b2 is elevated in HgCl2-induced renal inflammation; suppressed by CoQ10/albumin NP treatment.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC10669886" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b2 glycosylation is critical for secretion and receptor interaction.", "mechanism": "TGF-\u03b2 mediates fibrogenesis in HgCl2 toxicity; levels reduced by CoQ10/albumin NP treatment.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC10669886" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "\u03b1-SMA is a glycoprotein; glycosylation may affect its stability.", "mechanism": "\u03b1-SMA is upregulated in hepatic fibrosis; reduced by CoQ10/albumin NP treatment.", "protein": "Alpha-smooth muscle actin (\u03b1-SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC10669886" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "NF-\u03baB activity can be modulated by glycosylation of upstream receptors.", "mechanism": "NF-\u03baB activation drives inflammatory cytokine expression in HgCl2 toxicity; inhibited by CoQ10/albumin NP treatment.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC10669886" }, { "confidence": "medium", "disease": "Mercuric chloride-induced hepatorenal toxicity", "glycan_involvement": "BSA glycosylation may influence nanoparticle formation and bio-distribution.", "mechanism": "BSA nanoparticles act as drug carriers and have intrinsic antioxidant properties.", "protein": "Bovine serum albumin (BSA)", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typicall", "gene_name": "ALB", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02769" }, "relationship_type": "protective", "source_pmcid": "PMC10669886" }, { "confidence": "medium", "disease": "Hepatic apoptosis", "glycan_involvement": "Bcl-2 glycosylation may affect its anti-apoptotic function.", "mechanism": "Bcl-2 is downregulated in HgCl2 toxicity; upregulated by CoQ10/albumin NP treatment, reducing apoptosis.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC10669886" }, { "confidence": "medium", "disease": "Renal apoptosis", "glycan_involvement": "Bax glycosylation may influence mitochondrial targeting.", "mechanism": "Bax is upregulated in HgCl2-induced apoptosis; suppressed by CoQ10/albumin NP treatment.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC10669886" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding and clearance.", "mechanism": "LDL levels are elevated in hypercholesterolemia; CDF reduces LDL cholesterol in rats.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL is glycosylated; glycosylation modulates function and anti-atherogenic properties.", "mechanism": "HDL levels inversely correlate with cardiovascular risk; CDF did not significantly alter HDL.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "ApoB glycosylation affects LDL assembly and clearance.", "mechanism": "ApoB is the main protein of LDL; reduction in LDL by CDF implies reduced ApoB.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "ApoA1 glycosylation modulates HDL function.", "mechanism": "ApoA1 is the main protein of HDL; HDL levels are associated with CVD risk.", "protein": "Apolipoprotein A-I (ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Liver Steatosis (Fatty Liver)", "glycan_involvement": "ALP is glycosylated; glycosylation affects stability and activity.", "mechanism": "ALP is a marker of liver function; no significant change with CDF, indicating safety.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Liver Steatosis (Fatty Liver)", "glycan_involvement": "AST is glycosylated; glycosylation may affect secretion.", "mechanism": "AST is a marker of liver injury; unchanged with CDF, supporting hepatoprotection.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Liver Steatosis (Fatty Liver)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion.", "mechanism": "ALT is a marker of liver injury; unchanged with CDF, supporting hepatoprotection.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL glycosylation modulates receptor-mediated clearance.", "mechanism": "Elevated LDL is causal in atherosclerosis; CDF reduces LDL, lowering risk.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "LDL glycosylation may influence diabetic dyslipidemia.", "mechanism": "Elevated LDL is a risk factor for diabetes complications; CDF reduces LDL and glucose.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC10669986" }, { "confidence": "medium", "disease": "Liver Steatosis (Fatty Liver)", "glycan_involvement": "LDL glycosylation affects hepatic uptake.", "mechanism": "High LDL promotes hepatic lipid accumulation; CDF reduces liver cholesterol and lipids.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC10669986" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated serum ALP indicates liver injury due to MSG; reduced by Lepidium sativum seed intervention.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "AST is glycosylated; glycosylation may affect serum half-life.", "mechanism": "Increased AST reflects hepatocellular injury from MSG; normalized by Lepidium sativum seeds.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "ALT is glycosylated; glycosylation impacts secretion.", "mechanism": "ALT elevation marks necrotic liver injury from MSG; reduced by Lepidium sativum seeds.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability.", "mechanism": "Serum albumin decreases with liver injury; restored by Lepidium sativum seeds.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "Globulins are glycoproteins; glycosylation modulates immune function.", "mechanism": "Globulin levels altered in liver dysfunction; improved by Lepidium sativum seeds.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "SOD is glycosylated; glycosylation influences antioxidant activity.", "mechanism": "SOD activity decreases with MSG-induced oxidative stress; restored by Lepidium sativum seeds.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "CAT is glycosylated; glycosylation affects enzyme stability.", "mechanism": "CAT activity reduced by MSG-induced oxidative stress; improved by Lepidium sativum seeds.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "GR is glycosylated; glycosylation modulates redox function.", "mechanism": "GR activity inhibited by MSG; normalized by Lepidium sativum seeds.", "protein": "Glutathione reductase (GR)", "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "HDL-c contains glycoproteins (e.g., ApoA1); glycosylation affects lipid transport.", "mechanism": "MSG reduces HDL-c; Lepidium sativum seeds increase HDL-c, indicating improved lipid metabolism.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "LDL-c contains glycoproteins (e.g., ApoB); glycosylation modulates receptor binding.", "mechanism": "MSG increases LDL-c; Lepidium sativum seeds decrease LDL-c, reducing cardiovascular risk.", "protein": "Low-density lipoprotein cholesterol (LDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC10670087" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "HER3 is a 180 kDa glycoprotein; glycosylation is essential for its function and ligand binding.", "mechanism": "HER3 is overexpressed in breast cancer and its soluble forms can be detected in serum; associated with progression and chemoresistance.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Triple negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation affects HER3 isoform secretion and function.", "mechanism": "HER3 isoforms promote colonization and proliferation of TNBC metastases.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "Glycosylation modulates dimerization and ligand binding.", "mechanism": "HER3 forms heterodimers with HER2, activating oncogenic signaling and contributing to resistance to trastuzumab.", "protein": "HER3 (ErbB3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation required for HER3 stability and function.", "mechanism": "HER3 is overexpressed in ovarian cancer.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation required for HER3 stability and function.", "mechanism": "HER3 is overexpressed in bladder cancer.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation required for HER3 stability and function.", "mechanism": "HER3 is overexpressed in prostate cancer.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation required for HER3 stability and function.", "mechanism": "HER3 is overexpressed in melanoma.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Glycosylation required for HER3 stability and function.", "mechanism": "HER3 is overexpressed in neuroblastoma.", "protein": "HER3 (ErbB3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "High serum Aurora A predicts better response to neoadjuvant therapy (higher pCR rate); tissue overexpression associated with resistance and poor prognosis.", "protein": "Aurora A (AURKA)", "protein_enriched": { "function": "Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Ass", "gene_name": "AURKA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14965" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Serum TK1 correlates with disease stage and poor prognosis, but not predictive for neoadjuvant therapy response in this study.", "protein": "Thymidine kinase 1 (TK1)", "protein_enriched": { "function": "Cell-cycle-regulated enzyme of importance in nucleotide metabolism (PubMed:9575153). Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate (PubMed", "gene_name": "TK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04183" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670120" }, { "confidence": "high", "disease": "Testicular Germ Cell Tumor (TGCT)", "glycan_involvement": "PD-L1 stabilization and upregulation in cancer stem cells is mediated by N-glycosylation via STT3.", "mechanism": "PD-L1 is highly expressed in TGCT subtypes; anti-PD1/PD-L1 therapy is considered but response is limited.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "high", "disease": "Renal Cell Carcinoma (RCC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1, enhancing immune escape.", "mechanism": "PD-L1 expression modulates immune evasion; anti-PD1/PD-L1 therapy used in RCC.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma (RCC)", "glycan_involvement": "Glycosylation affects antigen presentation and immunogenicity.", "mechanism": "HSPPC-96-peptide complex used as a cancer vaccine; failed to show broad efficacy.", "protein": "Heat Shock Protein 96 (HSPPC-96/gp96)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Ganglioside glycan conjugation impacts immune recognition.", "mechanism": "GM2-KLH21 vaccine tested in adjuvant melanoma; ineffective and potentially detrimental.", "protein": "GM2-KLH21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect antigenicity and immune response.", "mechanism": "MAGE-A3 protein vaccine failed to improve relapse-free survival in melanoma.", "protein": "MAGE-A3", "protein_enriched": { "function": "May be involved in transcriptional regulation through interaction with SNW1 and recruiting histone deactelyase HDAC1. May inhibit notch intracellular domain (NICD) transactivation. May play a role in ", "gene_name": "MAGEA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P43355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Renal Cell Carcinoma (RCC)", "glycan_involvement": "Glycosylation influences immunogenicity of 5T4.", "mechanism": "5T4 antigen delivered by Trovax vaccine; no survival benefit in RCC.", "protein": "5T4", "protein_enriched": { "function": "May function as an inhibitor of Wnt/beta-catenin signaling by indirectly interacting with LRP6 and blocking Wnt3a-dependent LRP6 internalization", "gene_name": "TPBG", "glycan_count": 22, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G05724UK", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G05049YU", "G72747WU", "G30740WO", "G06247RL", "G11629QQ", "G12341GU", "G20312EM", "G27058EU", "G57776ZS", "G70232NH", "G79666IR", "G80479JV", "G93718GY", "G53434XO", "G43417UB", "G85677PP", "G49108TO" ], "uniprot_id": "Q13641" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "high", "disease": "Cancer (general, stem cell origin)", "glycan_involvement": "Glycosylation modulates HLA-G stability and immune interactions.", "mechanism": "HLA-G expression in stem cells and cancer stem cells confers immune privilege.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "protective/immune evasion", "source_pmcid": "PMC10670143" }, { "confidence": "high", "disease": "Microsatellite Instability (MSI) Tumors", "glycan_involvement": "N-glycosylation of PD-L1 enhances its function.", "mechanism": "MSI tumors with high PD-L1 respond better to immunotherapy.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Immune-mediated Colitis", "glycan_involvement": "Glycosylation status may affect tissue-specific toxicity.", "mechanism": "PD-L1 targeting in cancer stem cells can also affect normal stem cells, leading to colitis.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "causal (immunotherapy toxicity)", "source_pmcid": "PMC10670143" }, { "confidence": "medium", "disease": "Autoimmune Disease", "glycan_involvement": "Glycosylation influences immune recognition and cross-reactivity.", "mechanism": "Effective immunotherapy against PD-L1 can trigger autoimmunity due to shared antigens with stem cells.", "protein": "PD-L1 (Programmed death-ligand 1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10670143" }, { "confidence": "high", "disease": "Community-Acquired Pneumonia (CAP)", "glycan_involvement": "MBL recognizes mannan-type polysaccharides on pathogens via its glycosylated lectin domain.", "mechanism": "MBL deficiency is associated with increased susceptibility and severity of CAP in children.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "MBL glycosylation enables pathogen recognition and complement activation.", "mechanism": "MBL deficiency increases risk of sepsis and septic shock in CAP patients.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10670250" }, { "confidence": "medium", "disease": "Acute Respiratory Failure", "glycan_involvement": "MBL glycosylation is essential for pathogen binding and immune activation.", "mechanism": "Low MBL levels are associated with higher incidence of acute respiratory failure in CAP.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "MBL glycosylation mediates complement activation.", "mechanism": "MBL deficiency correlates with increased SIRS in CAP.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "medium", "disease": "Local Complications of CAP", "glycan_involvement": "MBL glycosylation facilitates pathogen opsonization.", "mechanism": "MBL deficiency is linked to higher rates of pleurisy, necrotizing pneumonia, and lung abscess.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Community-Acquired Pneumonia (CAP)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Elevated CRP (>100 mg/L) predicts severe CAP and complications.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP glycosylation modulates immune response.", "mechanism": "High CRP levels are associated with increased risk of sepsis in CAP.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Community-Acquired Pneumonia (CAP)", "glycan_involvement": "PCT is glycosylated; glycosylation may affect secretion and stability.", "mechanism": "Elevated PCT (>10 ng/mL) is a strong predictor of severe CAP and systemic complications.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "PCT glycosylation may influence its biomarker properties.", "mechanism": "High PCT levels are predictive of sepsis and septic shock in CAP.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "medium", "disease": "Septic Shock", "glycan_involvement": "MBL glycosylation is critical for complement activation and pathogen clearance.", "mechanism": "MBL deficiency is associated with increased risk and severity of septic shock in CAP.", "protein": "Mannose-Binding Lectin (MBL)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670250" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "O-glycosylation creates protective mucosal layer; degradation by A. muciniphila stimulates mucin production.", "mechanism": "Mucin forms a glycoprotein-rich barrier reducing translocation of proinflammatory LPS.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Intestinal permeability ('leaky gut')", "glycan_involvement": "O-glycosylation of mucin is essential for barrier function.", "mechanism": "Mucin maintains epithelial barrier integrity, preventing increased permeability.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "Glycosylation affects cytokine stability and secretion.", "mechanism": "Elevated serum IL-6 is part of the proinflammatory index.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "Elevated TNF-\u03b1 is associated with increased inflammation.", "protein": "Tumor Necrosis Factor alpha (TNF-\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "Glycosylation influences anti-inflammatory function.", "mechanism": "Higher IL-10 is associated with lower proinflammatory index.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Higher adiponectin correlates with reduced inflammation and metabolic risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "medium", "disease": "Intestinal permeability ('leaky gut')", "glycan_involvement": "Glycosylation stabilizes junctional complexes.", "mechanism": "ZO proteins maintain tight junctions, reducing permeability.", "protein": "Zonula Occludens (ZO-1, ZO-2, ZO-3)", "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "medium", "disease": "Intestinal permeability ('leaky gut')", "glycan_involvement": "Glycosylation affects localization and function.", "mechanism": "Occludin is essential for tight junction integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation provides substrate for beneficial microbiota.", "mechanism": "A. muciniphila-mediated mucin degradation supports barrier function, reducing obesity-related inflammation.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Altered glycosylation linked to disease susceptibility.", "mechanism": "Mucin barrier limits immune activation and inflammation.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC10670599" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Overexpression of sialylated glycan structure on cell surface; target for antibody binding.", "mechanism": "GD2 is highly expressed on neuroblastoma cells and targeted by anti-GD2 antibodies (e.g., Dinutuximab) for immunotherapy.", "protein": "GD2 (ganglioside GD2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Tumor-associated sialylated glycan; target for immunotherapy.", "mechanism": "GD2 is overexpressed in melanoma, enabling antibody-based and CAR-T therapies.", "protein": "GD2 (ganglioside GD2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Small cell lung cancer", "glycan_involvement": "Aberrant ganglioside expression on tumor cells.", "mechanism": "GD2 is expressed in small cell lung cancer; anti-GD2 therapies and CAR-T cells are under investigation.", "protein": "GD2 (ganglioside GD2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Elevated sialylated glycan on tumor cell surface; potential target for therapy.", "mechanism": "GD3 is highly enriched in GBM tissue and may promote angiogenesis and tumor growth.", "protein": "GD3 (ganglioside GD3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Anaplastic ganglioglioma", "glycan_involvement": "Tumor-specific sialylated glycan enrichment.", "mechanism": "GD3 is >50% of ganglioside content in anaplastic ganglioglioma, distinguishing tumor from normal tissue.", "protein": "GD3 (ganglioside GD3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Shed sialylated glycan detectable in serum.", "mechanism": "Elevated serum GM3 correlates with breast cancer presence and progression.", "protein": "GM3 (ganglioside GM3)", "relationship_type": "biomarker", "source_pmcid": "PMC10670608" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Desialylation of gangliosides alters signaling.", "mechanism": "Increased NEU3 expression promotes EGF receptor activation and tumor cell invasion.", "protein": "NEU3 (Sialidase-3)", "protein_enriched": { "function": "Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosac", "gene_name": "NEU3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UQ49" }, "relationship_type": "causal", "source_pmcid": "PMC10670608" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Enhanced sialylation of gangliosides on cancer cells.", "mechanism": "Upregulation of GD3 synthase via NF\u03baB pathway increases GD3, promoting tumor growth.", "protein": "ST8SIA1 (GD3 synthase)", "protein_enriched": { "function": "Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-lin", "gene_name": "ST8SIA2", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q92186" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Acute myeloid leukemia", "glycan_involvement": "Siglec recognizes sialylated glycans on leukemic cells.", "mechanism": "CD33 is targeted by antibody-drug conjugates (e.g., gemtuzumab ozogamicin) for AML therapy.", "protein": "CD33 (Siglec-3)", "protein_enriched": { "function": "Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state (PubMed:10611343, PubMed:11320212, PubM", "gene_name": "CD33", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G59626AS", "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "P20138" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "medium", "disease": "Neuroblastoma, Osteosarcoma, Small cell lung cancer", "glycan_involvement": "Immune checkpoint via sialylated glycan\u2013siglec interaction.", "mechanism": "Blocking Siglec-7/9 interactions with gangliosides (e.g., GD2) enhances anti-tumor immunity and reduces tumor burden.", "protein": "Siglec-7/Siglec-9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670608" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered N-glycosylation patterns in PSA are associated with prostate cancer aggressiveness.", "mechanism": "PSA levels are used to monitor prostate cancer progression and response to therapy.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC10670652" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation affects E-cadherin stability and cell adhesion.", "mechanism": "Downregulation of E-cadherin promotes metastasis and invasion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC10670652" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation is essential for P-glycoprotein function and drug efflux.", "mechanism": "Naproxen targets P-glycoprotein, reducing drug resistance.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation modulates VEGF secretion and receptor binding.", "mechanism": "Celecoxib reduces VEGF, inhibiting angiogenesis and tumor growth.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation is critical for EGFR maturation and ligand binding.", "mechanism": "Celecoxib inhibits EGFR signaling, reducing proliferation.", "protein": "Epidermal growth factor receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation is required for IL-6 secretion and receptor interaction.", "mechanism": "IL-6 promotes tumor progression and resistance; NSAIDs suppress IL-6 signaling.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC10670652" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation affects COX-2 stability and activity.", "mechanism": "COX-2 overexpression drives inflammation and tumorigenesis; NSAIDs inhibit COX-2.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Aspirin activates EP3, which has anti-tumor properties.", "protein": "Prostaglandin E2 receptor EP3", "protein_enriched": { "function": "Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important ", "gene_name": "PTGER1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P34995" }, "relationship_type": "protective", "source_pmcid": "PMC10670652" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may affect Bcl-2 stability.", "mechanism": "NSAIDs downregulate Bcl-2, promoting apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may regulate survivin localization.", "mechanism": "Aspirin and celecoxib downregulate survivin, enhancing apoptosis.", "protein": "Survivin (BIRC5)", "protein_enriched": { "function": "Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a c", "gene_name": "BIRC5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15392" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670652" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Not specified", "mechanism": "Upregulated in airway epithelium; promotes Th2 cytokines and airway remodeling via PI3K/AKT pathway.", "protein": "Cystatin SN (CST1)", "protein_enriched": { "function": "Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Cysta", "gene_name": "CST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01037" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Chronic rhinosinusitis (CRS)", "glycan_involvement": "Not specified", "mechanism": "Highly expressed in nasal epithelium and mucus of CRS patients; marker of Th2 inflammation.", "protein": "Cystatin SN (CST1)", "protein_enriched": { "function": "Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Cysta", "gene_name": "CST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01037" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Not specified", "mechanism": "Promotes tumor progression/metastasis by activating PI3K/AKT, stabilizing GPX4, and neutralizing Cystatin C inhibition of cathepsin B.", "protein": "Cystatin SN (CST1)", "protein_enriched": { "function": "Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Cysta", "gene_name": "CST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01037" }, "relationship_type": "causal/pro-tumor", "source_pmcid": "PMC10670837" }, { "confidence": "medium", "disease": "Cancer (prostate, gastric)", "glycan_involvement": "Not specified", "mechanism": "Upregulation correlates with tumor metastasis; may promote EMT via TGF-\u03b2 pathway.", "protein": "Cystatin SA (CST2)", "protein_enriched": { "function": "Thiol protease inhibitor", "gene_name": "CST2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09228" }, "relationship_type": "biomarker/pro-tumor", "source_pmcid": "PMC10670837" }, { "confidence": "medium", "disease": "Cancer (esophageal, colon, gastric)", "glycan_involvement": "Not specified", "mechanism": "Overexpression associated with poor prognosis; promotes EMT via ELFN2 upregulation.", "protein": "Cystatin S (CST4)", "protein_enriched": { "function": "This protein strongly inhibits papain and ficin, partially inhibits stem bromelain and bovine cathepsin C, but does not inhibit porcine cathepsin B or clostripain. Papain is inhibited non-competitivel", "gene_name": "CST4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01036" }, "relationship_type": "biomarker/pro-tumor", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Cancer (colon, gastric, prostate)", "glycan_involvement": "Not specified", "mechanism": "Inhibits Wnt/\u03b2-catenin and c-MYC; extends cell cycle, reduces proliferation/migration; induced by vitamin D and p53.", "protein": "Cystatin D (CST5)", "protein_enriched": { "function": "Cysteine proteinase inhibitor that possibly plays a protective role against proteinases present in the oral cavity. The order of preference for inhibition is cathepsin S > cathepsin H > cathepsin L > ", "gene_name": "CST5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P28325" }, "relationship_type": "protective/antitumor", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Not specified", "mechanism": "Dysregulation or mutation leads to amyloid plaque formation; regulates cathepsin B-mediated amyloid beta degradation.", "protein": "Cystatin C (CST3)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Cancer (pancreatic, breast, leukemia)", "glycan_involvement": "Not specified", "mechanism": "Strong inhibitor of cathepsin B; suppresses cell migration, invasion, and TGF-\u03b2 signaling.", "protein": "Cystatin C (CST3)", "relationship_type": "protective/antitumor", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Cancer (breast, prostate, brain, cervical)", "glycan_involvement": "N-glycosylation at N137; involved in lysosomal targeting and function.", "mechanism": "Hypermethylated and downregulated in tumors; inhibits legumain, cathepsin B/K, and NF-\u03baB signaling; suppresses bone metastasis.", "protein": "Cystatin E/M (CST6)", "relationship_type": "protective/antitumor", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Cancer (liver, oral, brain)", "glycan_involvement": "N-glycosylation at N62, N115; required for lysosomal targeting and activation.", "mechanism": "Immunosuppressive; high levels reduce NK/CD8+ T cell cytotoxicity, associated with poor prognosis.", "protein": "Cystatin F (CST7)", "protein_enriched": { "function": "Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine (Gl", "gene_name": "EXTL2", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G13131HA", "G80920RR", "G83646BJ", "G86880BF" ], "uniprot_id": "Q9UBQ6" }, "relationship_type": "causal/pro-tumor", "source_pmcid": "PMC10670837" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP reflects systemic inflammation, associated with increased AF risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10670853" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and activity.", "mechanism": "IL-6 promotes inflammation and atrial remodeling, increasing AF risk.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "IL-2 glycosylation affects secretion and bioactivity.", "mechanism": "IL-2 elevation in cancer and AF patients contributes to immune activation and arrhythmogenesis.", "protein": "Interleukin-2", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation influences IL-8 chemotactic function.", "mechanism": "IL-8 is elevated in AF and cancer, reflecting pro-inflammatory state.", "protein": "Interleukin-8", "relationship_type": "biomarker", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation modulates TNF-alpha receptor interactions.", "mechanism": "TNF-alpha drives inflammation and cardiac remodeling, promoting AF.", "protein": "Tumor necrosis factor alpha", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation affects MIF stability and immune signaling.", "mechanism": "Elevated MIF in AF and cancer reflects inflammatory activation.", "protein": "Macrophage migration inhibitory factor", "protein_enriched": { "function": "Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens (PubMed:15908412, PubMed:17443469, PubMed:23776208). The expression of MIF at sites of inflammation suggests a r", "gene_name": "MIF", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G98297PB" ], "uniprot_id": "P14174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation may regulate NLRP3 assembly and activation.", "mechanism": "NLRP3 activation leads to IL-1\u03b2 release, promoting inflammation and AF onset.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Cardiac arrhythmia", "glycan_involvement": "Connexin glycosylation affects gap junction formation and function.", "mechanism": "Altered connexin expression/glycosylation disrupts electrical conduction, leading to arrhythmias.", "protein": "Connexins", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation regulates metalloproteinase secretion and activity.", "mechanism": "ROS-induced metalloproteinase activation remodels extracellular matrix, promoting fibrosis and AF.", "protein": "Metalloproteinases", "relationship_type": "causal", "source_pmcid": "PMC10670853" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation modulates platelet adhesion and aggregation.", "mechanism": "Altered platelet glycoproteins contribute to bleeding risk in cancer patients on anticoagulants.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10670853" }, { "confidence": "high", "disease": "Bladder barrier dysfunction", "glycan_involvement": "N-glycosylation critical for plaque formation and barrier function.", "mechanism": "Uroplakins form glycosylated plaques essential for urothelial impermeability; disruption increases permeability.", "protein": "Uroplakins", "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Bladder barrier dysfunction", "glycan_involvement": "Glycosylation may affect localization/function; not directly detailed.", "mechanism": "Increased CLDN2 expression raises cation permeability, leading to leaky urothelium.", "protein": "Claudin 2 (CLDN2)", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95049" }, "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "medium", "disease": "Interstitial cystitis/bladder pain syndrome (IC/BPS)", "glycan_involvement": "Not specified.", "mechanism": "Overexpression increases K+ leakage, sensitizing nerves and causing pain.", "protein": "Claudin 2 (CLDN2)", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95049" }, "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Bladder barrier dysfunction", "glycan_involvement": "O-glycosylation (core 2/4) critical for mucin barrier function.", "mechanism": "Mucins form a glycosylated barrier; loss reduces protection against urine components.", "protein": "Mucins", "relationship_type": "protective", "source_pmcid": "PMC10670955" }, { "confidence": "medium", "disease": "Bladder barrier dysfunction", "glycan_involvement": "O-glycosylation (core 2/4) of mucins.", "mechanism": "Reduced Gcnt3 expression in females leads to shorter O-glycan branches on mucins, weakening the barrier.", "protein": "Glycosyltransferases (Gcnt3)", "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "medium", "disease": "Bladder barrier dysfunction", "glycan_involvement": "Not specified.", "mechanism": "Reduced moesin in females impairs actin cytoskeleton, destabilizing cell junctions.", "protein": "Moesin (MSN)", "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Bladder barrier dysfunction", "glycan_involvement": "Glycosaminoglycan chains essential for function.", "mechanism": "Proteoglycans in glycocalyx prevent solute/bacterial adhesion; loss increases permeability.", "protein": "Proteoglycans", "relationship_type": "protective", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Interstitial cystitis/bladder pain syndrome (IC/BPS)", "glycan_involvement": "Direct replacement of glycan layer.", "mechanism": "GAG replenishment restores deficient glycocalyx, improving barrier function.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670955" }, { "confidence": "medium", "disease": "Chronic cystitis", "glycan_involvement": "Affects N- and O-glycosylation patterns.", "mechanism": "Sex-specific expression changes in glycosyltransferases reflect altered glycoprotein profiles in chronic inflammation.", "protein": "Glycosyltransferases (general)", "relationship_type": "biomarker", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Bladder barrier dysfunction", "glycan_involvement": "Loss of glycosylated surface layer.", "mechanism": "Reduced glycocalyx in females correlates with increased permeability and susceptibility to inflammation.", "protein": "Glycocalyx (composite of glycoproteins/glycolipids)", "relationship_type": "causal", "source_pmcid": "PMC10670955" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "FXI is a glycoprotein; glycosylation required for secretion and function, but specific glycan changes not discussed.", "mechanism": "Elevated FXI (>150%) is strongly associated with symptomatic thrombotic APS; high FXI amplifies coagulation in presence of aPL.", "protein": "Factor XI (FXI)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Thromboembolic Disease", "glycan_involvement": "FXI glycosylation is essential for plasma stability; not specifically altered in disease context here.", "mechanism": "High FXI levels increase risk of both venous and arterial thrombosis.", "protein": "Factor XI (FXI)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Asymptomatic aPL Carrier State (AaPL)", "glycan_involvement": "No specific glycan modification described; FXI glycosylation required for function.", "mechanism": "Low FXI (<70%), often due to inhibitors, is overrepresented in AaPL and confers protection against thrombosis.", "protein": "Factor XI (FXI)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Congenital FXI Deficiency", "glycan_involvement": "Congenital deficiency may affect glycosylation indirectly via protein absence.", "mechanism": "Genetic FXI deficiency leads to mild bleeding but strong protection from thrombosis.", "protein": "Factor XI (FXI)", "relationship_type": "causal/protective", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Venous Thrombosis", "glycan_involvement": "No specific glycan change described.", "mechanism": "High FXI is associated with increased risk of venous thromboembolism in aPL carriers.", "protein": "Factor XI (FXI)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Arterial Thrombosis", "glycan_involvement": "No specific glycan change described.", "mechanism": "High FXI is associated with increased risk of arterial thrombosis in aPL carriers.", "protein": "Factor XI (FXI)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Therapeutic targeting does not specifically alter glycosylation.", "mechanism": "FXI inhibition (by drugs or aPL-induced inhibitors) is proposed as a thromboprotective strategy in APS.", "protein": "Factor XI (FXI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670960" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "\u03b22GP1 is a glycoprotein; glycosylation is essential for its function but not specifically altered in APS here.", "mechanism": "\u03b22GP1 inhibits thrombin activation of FXI; anti-\u03b22GP1 antibodies modulate this effect, influencing thrombosis risk.", "protein": "\u03b2-2-glycoprotein 1 (\u03b22GP1)", "relationship_type": "modulator", "source_pmcid": "PMC10670960" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "No specific glycan change described.", "mechanism": "FXI activity inversely correlates with anti-\u03b22GP1 antibody titers; lower FXI activity may reflect protective effect.", "protein": "Factor XI (FXI)", "relationship_type": "biomarker", "source_pmcid": "PMC10670960" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation required for FXI secretion and function.", "mechanism": "FXI is a phospholipid-binding glycoprotein; its interaction with aPL and \u03b22GP1 modulates thrombosis risk.", "protein": "Factor XI (FXI)", "relationship_type": "causal", "source_pmcid": "PMC10670960" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "FVIII is a heavily N-glycosylated glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Deficiency or absence of FVIII leads to impaired blood clotting.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "causal", "source_pmcid": "PMC10670993" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Therapeutic FVIII glycosylation affects immunogenicity and half-life.", "mechanism": "Replacement therapy with recombinant or plasma-derived FVIII corrects clotting defects.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670993" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation status can influence assay detection and activity.", "mechanism": "FVIII activity levels are used to diagnose and monitor hemophilia A severity.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "biomarker", "source_pmcid": "PMC10670993" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "hAFMSC-derived FVIII is glycosylated, supporting its secretion and function.", "mechanism": "In utero transplantation of hAFMSCs producing FVIII improves coagulation in FVIII KO mice.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670993" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "Proper glycosylation may reduce immunogenicity of FVIII.", "mechanism": "Prenatal exposure to FVIII via hAFMSC engraftment induces immune tolerance, reducing inhibitor development.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "protective", "source_pmcid": "PMC10670993" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "VSVG is a glycoprotein; glycosylation is required for its fusogenic activity.", "mechanism": "VSVG expression enhances MSC fusion with target cells, improving regenerative therapy outcomes.", "protein": "Vesicular Stomatitis Virus Glycoprotein (VSVG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670993" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation patterns influence FVIII immunogenicity.", "mechanism": "Development of FVIII-neutralizing antibodies (inhibitors) impairs efficacy of replacement therapy.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "causal", "source_pmcid": "PMC10670993" }, { "confidence": "low", "disease": "Osteogenesis Imperfecta", "glycan_involvement": "N/A", "mechanism": "No direct relationship; referenced as a model for in utero therapy.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "none", "source_pmcid": "PMC10670993" }, { "confidence": "low", "disease": "Alpha Thalassemia", "glycan_involvement": "N/A", "mechanism": "No direct relationship; referenced as a model for in utero therapy.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "none", "source_pmcid": "PMC10670993" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "Emicizumab is a glycoprotein antibody; glycosylation affects its pharmacokinetics.", "mechanism": "Emicizumab, a bispecific antibody, mimics FVIII function to restore coagulation.", "protein": "Coagulation Factor VIII (FVIII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10670993" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects APOE stability and receptor interactions.", "mechanism": "Regulates lipid metabolism and influences inflammation; upregulation associated with improved HDL-c and reduced risk.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC10671063" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycosylation modulates APOE isoform function and aggregation.", "mechanism": "APOE isoforms (especially APOE4) modulate neuroinflammation and oxidative stress.", "protein": "Apolipoprotein E", "relationship_type": "causal", "source_pmcid": "PMC10671063" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation may affect APOE's metabolic activity.", "mechanism": "APOE influences lipid and glucose metabolism, impacting diabetes risk.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC10671063" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation state may alter immune interactions.", "mechanism": "APOE modulates immune response and inflammation, which are linked to cancer progression.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC10671063" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "N-glycosylation required for ACE enzymatic activity and stability.", "mechanism": "ACE regulates blood pressure via the renin\u2013angiotensin system; upregulation increases risk unless balanced by ACE2.", "protein": "Angiotensin I-Converting Enzyme", "relationship_type": "causal", "source_pmcid": "PMC10671063" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates ACE inhibitor binding.", "mechanism": "ACE is targeted by inhibitors to treat hypertension and reduce cardiovascular risk.", "protein": "Angiotensin I-Converting Enzyme", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671063" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "Glycosylation influences APOE's anti-inflammatory properties.", "mechanism": "APOE upregulation reduces inflammatory markers and cytokines.", "protein": "Apolipoprotein E", "relationship_type": "protective", "source_pmcid": "PMC10671063" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "N-glycosylation affects ACE's interaction with substrates.", "mechanism": "ACE activity can promote inflammation via angiotensin II production.", "protein": "Angiotensin I-Converting Enzyme", "relationship_type": "causal", "source_pmcid": "PMC10671063" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation enhances APOE's lipid transport function.", "mechanism": "Upregulation after Mediterranean diet increases HDL-c, lowering cardiovascular risk.", "protein": "Apolipoprotein E", "relationship_type": "protective", "source_pmcid": "PMC10671063" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation modulates ACE's metabolic effects.", "mechanism": "ACE activity linked to insulin resistance and metabolic syndrome.", "protein": "Angiotensin I-Converting Enzyme", "relationship_type": "biomarker", "source_pmcid": "PMC10671063" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ApoE structure and function.", "mechanism": "APOE*4 allele increases risk via lipid metabolism and A\u03b2 aggregation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10671071" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP processing and A\u03b2 generation.", "mechanism": "Mutations lead to increased A\u03b2 production and plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences CR1 function in immune response.", "mechanism": "CR1 variants affect A\u03b2 clearance and neuroinflammation.", "protein": "Complement receptor 1 (CR1)", "protein_enriched": { "function": "Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). Mediates the bi", "gene_name": "CR1", "glycan_count": 13, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22310AV", "G40834TG", "G45395BF", "G47748JZ", "G48414YA", "G54285KU", "G57888GL", "G82830MN", "G06356OH", "G27058EU", "G79666IR", "G86795LJ", "G49108TO" ], "uniprot_id": "P17927" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Lewy body dementia", "glycan_involvement": "Glycosylation required for CLU chaperone activity.", "mechanism": "CLU binds aggregated \u03b1-synuclein, possibly modulating toxicity.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects SORL1 trafficking and APP interaction.", "mechanism": "SORL1 variants modulate A\u03b2 peptide production.", "protein": "Sortilin-related receptor 1 (SORL1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10671071" }, { "confidence": "high", "disease": "Lewy body dementia", "glycan_involvement": "O-glycosylation may modulate SNCA aggregation.", "mechanism": "SNCA aggregation forms Lewy bodies; gene dosage increases risk.", "protein": "\u03b1-synuclein (SNCA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10671071" }, { "confidence": "high", "disease": "Lewy body dementia", "glycan_involvement": "N-glycosylation required for GBA folding and activity.", "mechanism": "GBA mutations reduce lysosomal degradation of \u03b1-synuclein.", "protein": "\u03b2-glucocerebrosidase (GBA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Cerebral amyloid angiopathy", "glycan_involvement": "Glycosylation may affect TTR stability and aggregation.", "mechanism": "TTR mutations promote amyloid deposition in cerebral vessels.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "causal", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Cerebral amyloid angiopathy", "glycan_involvement": "Glycosylation influences CST3 secretion and aggregation.", "mechanism": "CST3 mutations lead to amyloid deposition in vasculature.", "protein": "Cystatin C (CST3)", "relationship_type": "causal", "source_pmcid": "PMC10671071" }, { "confidence": "medium", "disease": "Cerebral amyloid angiopathy", "glycan_involvement": "Glycosylation modulates GSN stability and amyloidogenicity.", "mechanism": "GSN mutations cause amyloid formation in vessels.", "protein": "Gelsolin (GSN)", "protein_enriched": { "function": "Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly o", "gene_name": "GSN", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G43417UB", "G57321FI", "G29068FM", "G53434XO" ], "uniprot_id": "P06396" }, "relationship_type": "causal", "source_pmcid": "PMC10671071" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "N-glycosylation critical for folding and immune evasion.", "mechanism": "Structural glycoprotein mediating viral entry; recognized as PAMP by PRRs.", "protein": "E1", "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "N-glycosylation shields epitopes from neutralizing antibodies.", "mechanism": "Structural glycoprotein mediating viral entry and immune escape.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; interacts with glycosylated host proteins.", "mechanism": "Suppresses IFN response via SOCS induction and IRF1 repression; promotes persistence.", "protein": "Core (C)", "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; targets glycosylated host signaling proteins.", "mechanism": "Cleaves MAVS, TRIF, and Riplet, blocking IFN induction.", "protein": "NS3/NS4A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; may interact with glycosylated host factors.", "mechanism": "Cleaves TBK1/IKK\u03b5, subverting IRF3 phosphorylation and IFN-\u03b2 induction.", "protein": "NS2", "protein_enriched": { "function": "", "gene_name": "NS5b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O39930" }, "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; interacts with ER membrane glycoproteins.", "mechanism": "Binds STING, blocks STING\u2013MAVS interaction, suppressing IFN-\u03b2 activation.", "protein": "NS4B", "protein_enriched": { "function": "", "gene_name": "RNA polymerase gene", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O39933" }, "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; interacts with glycosylated host proteins.", "mechanism": "Inhibits IFN signaling via MyD88 sequestration, STAT1 inhibition, and PKR repression.", "protein": "NS5A", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O39934" }, "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "ISG15 is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Blocks TRIM25-mediated RIG-I ubiquitination, modulating IFN induction.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "protective", "source_pmcid": "PMC10671098" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "N-glycosylation shields viral epitopes, enabling persistence.", "mechanism": "Chronic infection via E1/E2-mediated immune evasion promotes carcinogenesis.", "protein": "E1/E2", "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "No direct glycosylation; interacts with glycosylated host proteins.", "mechanism": "Promotes apoptosis and immune suppression, contributing to liver scarring.", "protein": "Core (C)", "relationship_type": "causal", "source_pmcid": "PMC10671098" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "GCase is a glycoprotein with four N-linked glycans essential for folding and lysosomal targeting.", "mechanism": "Mutations in GBA1 cause misfolding and deficiency of GCase, leading to lysosomal accumulation of glucosylceramide and glucosylsphingosine.", "protein": "Glucocerebrosidase (GCase)", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "Contains glycosylation sites important for lysosomal function.", "mechanism": "Saposin C is required for GCase activation; deficiency leads to GD, often neuronopathic.", "protein": "Saposin C", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "Highly glycosylated; glycosylation affects trafficking and processing.", "mechanism": "Mutations in the saposin C domain of prosaposin cause GD.", "protein": "Prosaposin", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Action Myoclonus-Renal Failure (AMRF)", "glycan_involvement": "LIMP2 is glycosylated, which is important for lysosomal targeting.", "mechanism": "Mutations in SCARB2 impair GCase transport to lysosomes, causing AMRF with reduced GCase activity.", "protein": "LIMP2 (SCARB2)", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "GPNMB is glycosylated; glycosylation may affect secretion and stability.", "mechanism": "GPNMB is overproduced and secreted by Gaucher cells; levels correlate with disease severity and neuroinflammation.", "protein": "Glycoprotein non-metastatic B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC10671165" }, { "confidence": "medium", "disease": "Metachromatic Leukodystrophy", "glycan_involvement": "Glycosylation required for lysosomal function.", "mechanism": "Activated by saposin B; deficiency or mutation leads to disease.", "protein": "Arylsulfatase A", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "medium", "disease": "Krabbe Disease", "glycan_involvement": "Glycosylation required for lysosomal function.", "mechanism": "Activated by saposin A; deficiency leads to Krabbe disease.", "protein": "\u03b2-galactocerebrosidase", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "medium", "disease": "Farber Disease", "glycan_involvement": "Glycosylation required for lysosomal function.", "mechanism": "Activated by saposin D; deficiency leads to Farber disease.", "protein": "Ceramidase (ASAH1)", "relationship_type": "causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Parkinson Disease", "glycan_involvement": "Glycosylation affects GCase folding and lysosomal targeting.", "mechanism": "GD1 patients (GCase deficiency) are predisposed to Parkinson disease; GCase deficiency promotes \u03b1-synuclein aggregation.", "protein": "Glucocerebrosidase (GCase)", "relationship_type": "protective/causal", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "C5aR1 is glycosylated; glycosylation may affect receptor function.", "mechanism": "C5aR1 activation drives GlcCer-dependent inflammation; knockout reverses inflammation and prolongs survival in GD mice.", "protein": "Complement C5a receptor (C5aR1)", "protein_enriched": { "function": "Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:10636859, PubMed:15153520, PubMed:1847994, PubMed:29300009, PubMed:7622471, PubMed:8182049, PubMed:9553099). The ligand ", "gene_name": "C5AR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P21730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671165" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation increases molecular weight and antigenicity.", "mechanism": "CA125 is a tumor marker for ovarian cancer; its high N-glycosylation is used for detection.", "protein": "Mucin-16 (CA125)", "relationship_type": "biomarker", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation affects receptor function and ligand binding.", "mechanism": "LRP1 is highly glycosylated and involved in cell signaling and tumor progression.", "protein": "LRP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671238" }, { "confidence": "high", "disease": "Niemann\u2013Pick disease type C", "glycan_involvement": "N-glycosylation is critical for proper NPC1 function.", "mechanism": "NPC1 mutations disrupt cholesterol transport; glycosylation affects protein folding and trafficking.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "N-glycosylation regulates surface expression and function.", "mechanism": "NPC1L1 mediates cholesterol absorption; glycosylation modulates its activity.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671238" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation modulates receptor folding, trafficking, and signaling.", "mechanism": "GPCRs mediate hormone/neurotransmitter signaling; altered glycosylation affects receptor function.", "protein": "GPCRs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation influences ligand binding and receptor stability.", "mechanism": "GPCRs are involved in vascular and neuronal signaling; glycosylation impacts their activity.", "protein": "GPCRs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation alters receptor conformation and downstream signaling.", "mechanism": "GPCRs are implicated in tumor growth and metastasis; glycosylation status affects signaling.", "protein": "GPCRs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Immune disorders", "glycan_involvement": "N-glycosylation modulates peptide binding and T cell activation.", "mechanism": "MHC II glycosylation affects antigen presentation and immune response.", "protein": "MHC II", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Heparan sulfate-related disorders", "glycan_involvement": "N-glycosylation and GAG addition are essential for function.", "mechanism": "Glycosylation defects disrupt extracellular matrix and signaling.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC10671238" }, { "confidence": "medium", "disease": "Adhesion-related disorders", "glycan_involvement": "N-glycosylation affects protein folding and surface expression.", "mechanism": "Glycosylation modulates cell\u2013cell adhesion and migration.", "protein": "Cell adhesion molecules", "relationship_type": "causal", "source_pmcid": "PMC10671238" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations cause misfolding/aggregation, mitochondrial dysfunction, oxidative stress, and impaired energy supply.", "protein": "SOD1", "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "high", "disease": "ALS/FTD", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Hexanucleotide repeat expansions produce toxic dipeptide repeats, disrupt mitochondrial function, and impair mitophagy.", "protein": "C9ORF72", "protein_enriched": { "function": "Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP (PubMed:27103069, PubMed:27193190, PubMed:27617292, PubMe", "gene_name": "C9orf72", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96LT7" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "high", "disease": "ALS/FTD", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Aggregates disrupt mitochondrial dynamics, protein import, and RNA processing.", "protein": "TDP-43 (TARDBP)", "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "high", "disease": "ALS", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations cause cytoplasmic aggregation, mitochondrial dysfunction, and impaired axonal transport.", "protein": "FUS", "protein_enriched": { "function": "DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to ssRNA ", "gene_name": "FUS", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI", "G47950XN" ], "uniprot_id": "P35637" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "medium", "disease": "ALS2 (juvenile ALS)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Loss-of-function mutations impair Rab5-mediated mitochondrial quality control and increase susceptibility to oxidative stress.", "protein": "Alsin (ALS2)", "protein_enriched": { "function": "May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity)", "gene_name": "ALS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96Q42" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "medium", "disease": "ALS", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations disrupt ER-mitochondria contacts, calcium homeostasis, and axonal transport.", "protein": "VAPB", "protein_enriched": { "function": "Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMe", "gene_name": "VAPB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95292" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "high", "disease": "ALS", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations impair mitophagy, leading to accumulation of damaged mitochondria and cell death.", "protein": "Optineurin (OPTN)", "protein_enriched": { "function": "Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431). Links myosin VI to the Golgi", "gene_name": "OPTN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96CV9" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "medium", "disease": "ALS/FTD", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations disrupt MAM integrity, calcium homeostasis, and mitochondrial dynamics.", "protein": "Sigma-1 receptor (SIGMAR1)", "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "medium", "disease": "ALS/FTD", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Mutations impair mitophagy, mitochondrial clearance, and increase oxidative damage.", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "medium", "disease": "ALS/FTD", "glycan_involvement": "Interacts with glycoprotein 78 (gp78) in ERAD pathway.", "mechanism": "Mutations impair protein clearance, autophagy, and mitochondrial quality control.", "protein": "VCP", "relationship_type": "causal", "source_pmcid": "PMC10671245" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "YKL-40 is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Plasma YKL-40 levels are threefold higher in PD patients; correlate with mitochondrial bioenergetics (basal respiration, ATP production) and neuroinflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation enables extracellular matrix interactions.", "mechanism": "High YKL-40 expression associated with inflammatory brain profile and cognitive deterioration.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "medium", "disease": "Creutzfeldt\u2013Jakob disease", "glycan_involvement": "Glycosylation required for stability in plasma.", "mechanism": "Elevated plasma YKL-40 in CJD, especially at late stages; moderate discrimination potential.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "high", "disease": "Chronic inflammatory conditions", "glycan_involvement": "Glycosylation essential for secretion and immune modulation.", "mechanism": "Increased YKL-40 levels detected in chronic inflammation; reflects macrophage/microglial activation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Elevated YKL-40 levels in several solid tumors; involved in tumor processes.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "medium", "disease": "Atypical Parkinson's syndrome", "glycan_involvement": "Glycosylation required for function.", "mechanism": "YKL-40 levels lower in PD than in atypical Parkinson's syndrome, but higher than controls.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Reserve respiratory capacity (mitochondrial) sensitive to oxidative stress in dopaminergic disorders including schizophrenia; YKL-40 may reflect neuroinflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "low", "disease": "Restless legs syndrome", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Reserve respiratory capacity as a marker for dopaminergic disorders; YKL-40 may be involved.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "low", "disease": "Systemic sclerosis", "glycan_involvement": "Glycosylation required for stability.", "mechanism": "Regulated by lncRNAs/miR-30e/YKL-40 axis; posttranscriptional regulation suggested.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671493" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation required for biomarker utility.", "mechanism": "YKL-40 levels may serve as a tool to monitor clinical course and inflammatory activity in PD.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671493" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "Glycosylation required for secretion and stability; chitinase-like domain.", "mechanism": "Correlates with severe asthma, irreversible airway obstruction, and lung function decline.", "protein": "YKL-40 (human cartilage glycoprotein-39)", "relationship_type": "biomarker", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation critical for plasma stability and heme binding.", "mechanism": "Serum levels differentiate COPD from asthma; acute phase glycoprotein upregulated in inflammation.", "protein": "Hemopexin", "protein_enriched": { "function": "Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation", "gene_name": "HPX", "glycan_count": 236, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00875VP", "G00912UN", "G01650EU", "G02528FI", "G02886BB", "G04657PL", "G04854VP", "G05933EN", "G06247RL", "G06356OH", "G06853GH", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G14572XX", "G14994KB", "G15169WU", "G18647XP", "G20425TQ", "G22140GZ", "G22276PO", "G22310AV", "G22572EH", "G23294PN", "G23863VK", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G30769VJ", "G31118FR", "G31916IQ", "G36131WL", "G37818NZ", "G37868ZX", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G42358LZ", "G43223CG", "G44576HQ", "G45395BF", "G45504EY", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G47702MW", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55412XP", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G62165AG", "G63980BQ", "G64394MX", "G65019XG", "G66163OV", "G66621EA", "G68735SN", "G70232NH", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G72797UR", "G74772YG", "G75983OB", "G76417NN", "G78644BR", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82463GQ", "G82830MN", "G83555HU", "G84452RH", "G85144OK", "G86056PA", "G86182NS", "G86234IN", "G86752LQ", "G86795LJ", "G86880BF", "G87399DK", "G88374WZ", "G89205CJ", "G90093AU", "G90659AW", "G92135MA", "G92275SC", "G92406TI", "G94470IW", "G94917XT", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G00273SJ", "G14669DU", "G22768VO", "G60861FA", "G77669RF", "G89045VA", "G92551JA", "G57321FI", "G42962KI", "G44215PV", "G46687AB", "G60923RB", "G71146HJ", "G17015OC", "G29931IJ", "G43417UB", "G74722FL", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G01485JJ", "G02030ZB", "G10819WX", "G12745LE", "G14547CB", "G14972EH", "G15127JD", "G20528HD", "G20706XG", "G25418HZ", "G26915XM", "G27915IV", "G30248BL", "G30970QQ", "G31852PQ", "G31986NC", "G33416PL", "G35253PZ", "G37412TK", "G37509XX", "G37692EO", "G37995HC", "G39619TI", "G41071NU", "G43669FQ", "G43734MM", "G46524LG", "G54010QB", "G56284ZY", "G58087IP", "G58954YZ", "G60834IK", "G61256FT", "G62461SM", "G63381RX", "G67164EE", "G69521XL", "G71463BG", "G72398FA", "G72787SB", "G75798PH", "G76329HL", "G77547TA", "G78502KD", "G81124ET", "G81295CK", "G85269DF", "G85554PZ", "G85677PP", "G87389XI", "G89098OM", "G92081HT", "G98129XB", "G01160VV", "G05049YU", "G05724UK", "G05962QB", "G07246CJ", "G07755XJ", "G11911BT", "G12341GU", "G12579WK", "G15038BD", "G15664MX", "G17208MA", "G23505EP", "G30740WO", "G34989PA", "G35029YA", "G39188ZX", "G40206WX", "G41247ZX", "G44753VC", "G47950XN", "G49018RC", "G49642SA", "G49906RN", "G49955PK", "G56307ZW", "G59324HL", "G62765YT", "G64275UO", "G64527OM", "G68490OW", "G70101JE", "G70441OD", "G72790NZ", "G75418YA", "G76295SF", "G80920RR", "G83646BJ", "G84225JN", "G85282JO", "G87661QW", "G90734RJ", "G95977AE", "G96430BV" ], "uniprot_id": "P02790" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "Extensive O-glycosylation essential for gel formation and mucus properties.", "mechanism": "Overproduction leads to mucus plugging and airway obstruction.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "O-glycosylation regulates mucin polymerization and secretion.", "mechanism": "Increased levels contribute to mucus hypersecretion and airway obstruction.", "protein": "MUC5B", "protein_enriched": { "function": "Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus", "gene_name": "MUC5B", "glycan_count": 47, "glycosylation_sites_count": 38, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G62765YT", "G80920RR", "G84452RH", "G48414YA", "G66760KM", "G57321FI", "G64527OM", "G39188ZX", "G31852PQ", "G70822IO", "G75983OB", "G05724UK", "G06110VR", "G10773YW", "G29880MM", "G46687AB", "G82119TF", "G02030ZB", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G40142JY", "G42665KV", "G49582PC", "G58272ZE", "G63110FE", "G63628AV", "G63760GT", "G64973KT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G78315FS", "G79243QP", "G81006GJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q9HC84" }, "relationship_type": "causal", "source_pmcid": "PMC10671561" }, { "confidence": "medium", "disease": "Asthma-COPD Overlap (ACO)", "glycan_involvement": "N-glycosylation affects secretion and immune function.", "mechanism": "Serum/sputum levels distinguish asthma, COPD, and ACO; involved in inflammation.", "protein": "NGAL (Lipocalin 2)", "relationship_type": "biomarker", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "N-glycosylation modulates inhibitory activity and stability.", "mechanism": "High serum levels correlate with severe asthma and reduced lung function; promotes eosinophilic inflammation and M2 macrophage polarization.", "protein": "TIMP-1", "protein_enriched": { "function": "Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc co", "gene_name": "TIMP1", "glycan_count": 136, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01600VV", "G02030ZB", "G02661MY", "G03382KH", "G04657PL", "G05229BF", "G06356OH", "G07755XJ", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10944ZI", "G11314AS", "G11392CL", "G11870QZ", "G14994KB", "G20312EM", "G20751GZ", "G22310AV", "G23719VF", "G23863VK", "G25451PN", "G27058EU", "G28156XV", "G29580WD", "G29880MM", "G31852PQ", "G36379GD", "G37868ZX", "G39841VH", "G41071NU", "G41247ZX", "G42039DE", "G42124LM", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46687AB", "G49874UX", "G51413EV", "G57081YJ", "G57818FI", "G59358BQ", "G61256FT", "G62765YT", "G64409MC", "G66163OV", "G66504LK", "G66538GV", "G70375MX", "G71146HJ", "G71146MY", "G72667IM", "G72797UR", "G74724QE", "G75303RX", "G75983OB", "G76295SF", "G78454JO", "G79286RS", "G80333GO", "G80920RR", "G81263BG", "G83229XP", "G84452RH", "G84811LS", "G86795LJ", "G89417VQ", "G90093AU", "G90382BL", "G90575OW", "G91636VS", "G92275SC", "G94854LT", "G96079KC", "G96577RX", "G00912UN", "G02528FI", "G02815KT", "G05049YU", "G08293MJ", "G10339FR", "G10819WX", "G11629QQ", "G11911BT", "G12580WI", "G14972EH", "G15169WU", "G19379ID", "G24202BK", "G25713RA", "G26271XI", "G31483BB", "G34989PA", "G35253PZ", "G40834TG", "G41126SR", "G43734MM", "G44953PJ", "G46691LC", "G47644PP", "G47950XN", "G56284ZY", "G57776ZS", "G59626AS", "G60923RB", "G64527OM", "G68318VE", "G69521XL", "G70087PV", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G75607BQ", "G77122IZ", "G79666IR", "G80075MS", "G81198YO", "G82592ZH", "G83460ZZ", "G83555HU", "G83633GK", "G86880BF", "G87051GH", "G88374WZ", "G90659AW", "G92135MA", "G95177YH", "G95835XS", "G95977AE", "G49108TO" ], "uniprot_id": "P01033" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "N-glycosylation required for ECM incorporation and cell signaling.", "mechanism": "Serum levels reflect Th2-high asthma and airway remodeling.", "protein": "Periostin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10671561" }, { "confidence": "high", "disease": "Lung Fibrosis", "glycan_involvement": "Glycosylation influences ECM assembly and cell adhesion.", "mechanism": "ECM deposition drives subepithelial fibrosis and airway remodeling.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "causal", "source_pmcid": "PMC10671561" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Spike protein is heavily glycosylated, which modulates immune recognition and pathogenicity.", "mechanism": "Spike glycoprotein can induce cross-reaction with myocardial contractile proteins, contributing to myocarditis after infection or mRNA vaccination.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10671623" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "MMP-7 is glycosylated, affecting secretion and activity.", "mechanism": "Elevated MMP-7 expression in convalescents vaccinated with BNT162b2 suggests involvement in post-infection angiogenesis and tissue remodeling.", "protein": "MMP-7", "protein_enriched": { "function": "Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase", "gene_name": "MMP7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09237" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671623" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ADAMTS1 glycosylation modulates its anti-angiogenic activity.", "mechanism": "Increased ADAMTS1 expression in non-vaccinated convalescents may reflect anti-angiogenic response post-infection.", "protein": "ADAMTS1", "relationship_type": "biomarker", "source_pmcid": "PMC10671623" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "VEGFA glycosylation affects receptor binding and angiogenic potency.", "mechanism": "VEGFA upregulation (via HIF-1\u03b1) promotes abnormal angiogenesis and vascular permeability in COVID-19.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671623" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates vWF multimerization and function.", "mechanism": "Elevated plasma levels in COVID-19 patients indicate endothelial activation and increased thrombotic risk.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10671623" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation is essential for Factor VIII stability and activity.", "mechanism": "Increased plasma levels in COVID-19 patients contribute to hypercoagulability.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC10671623" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects SARS-CoV-2 binding and enzymatic activity.", "mechanism": "Loss of ACE2 activity in endothelial cells leads to RAAS imbalance, promoting vasoconstriction and thrombosis.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671623" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation modulates MMP-7 secretion and activity.", "mechanism": "MMP-7 involved in post-inflammatory myocardial remodeling in myocarditis.", "protein": "MMP-7", "protein_enriched": { "function": "Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase", "gene_name": "MMP7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09237" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671623" }, { "confidence": "medium", "disease": "Angiogenesis disorders", "glycan_involvement": "Glycosylation influences ADAMTS1 secretion and inhibitory function.", "mechanism": "ADAMTS1 acts as an anti-angiogenic factor, potentially limiting pathological angiogenesis post-COVID-19.", "protein": "ADAMTS1", "relationship_type": "protective", "source_pmcid": "PMC10671623" }, { "confidence": "low", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "Glycosylation patterns affect immunogenicity and antibody response.", "mechanism": "Spike glycoprotein may trigger immune-mediated thrombosis after vaccination.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10671623" }, { "confidence": "high", "disease": "COVID-19-associated acute kidney injury (AKI)", "glycan_involvement": "LAP is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated urinary LAP reflects acute proximal tubular injury in AKI during COVID-19.", "protein": "Leucine aminopeptidase (LAP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "high", "disease": "COVID-19-associated acute kidney injury (AKI)", "glycan_involvement": "Cystatin C is N-glycosylated, which may influence its serum half-life.", "mechanism": "Elevated plasma cystatin C predicts AKI and poor prognosis.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "N-glycosylation may affect cystatin C's renal clearance.", "mechanism": "High cystatin C levels are associated with increased mortality and ICU admission.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "suPAR is heavily N-glycosylated, influencing its plasma stability and immune interactions.", "mechanism": "Elevated plasma suPAR predicts severe disease, ICU admission, and mortality.", "protein": "Soluble urokinase plasminogen activator receptor (suPAR)", "protein_enriched": { "function": "Inhibits gastrointestinal motility and gastric acid secretion. Could function as a structural component of gastric mucus, possibly by stabilizing glycoproteins in the mucus gel through interactions wi", "gene_name": "TFF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92551JA" ], "uniprot_id": "Q03403" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "medium", "disease": "Multiorgan damage in COVID-19", "glycan_involvement": "N-glycosylation modulates suPAR's immune signaling.", "mechanism": "High suPAR reflects systemic inflammation and cytokine storm.", "protein": "Soluble urokinase plasminogen activator receptor (suPAR)", "protein_enriched": { "function": "Inhibits gastrointestinal motility and gastric acid secretion. Could function as a structural component of gastric mucus, possibly by stabilizing glycoproteins in the mucus gel through interactions wi", "gene_name": "TFF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92551JA" ], "uniprot_id": "Q03403" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "medium", "disease": "COVID-19-associated acute kidney injury (AKI)", "glycan_involvement": "NGAL is glycosylated, which may affect its renal handling.", "mechanism": "NGAL levels tended to be higher in AKI but not statistically significant in this cohort.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "low", "disease": "COVID-19-associated acute kidney injury (AKI)", "glycan_involvement": "CCL14 is glycosylated; glycosylation may affect secretion.", "mechanism": "Urinary CCL14 levels were not significantly different between AKI and non-AKI groups.", "protein": "Chemokine (C-C motif) ligand 14 (CCL14)", "protein_enriched": { "function": "Has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induces intracellular Ca(2+) changes and enzyme release, but no chemotaxis, at concentrations of 100-1", "gene_name": "CCL14", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "Q16627" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation may modulate LAP's urinary excretion.", "mechanism": "LAP may indicate ongoing tubular injury, a risk for CKD progression post-AKI.", "protein": "Leucine aminopeptidase (LAP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "N-glycosylation affects cystatin C's serum levels.", "mechanism": "Elevated cystatin C is a marker for CKD risk after AKI.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "medium", "disease": "COVID-19-associated acute kidney injury (AKI)", "glycan_involvement": "N-glycosylation affects suPAR's immune activity.", "mechanism": "suPAR levels did not distinguish AKI from non-AKI but predicted overall severity.", "protein": "Soluble urokinase plasminogen activator receptor (suPAR)", "protein_enriched": { "function": "Inhibits gastrointestinal motility and gastric acid secretion. Could function as a structural component of gastric mucus, possibly by stabilizing glycoproteins in the mucus gel through interactions wi", "gene_name": "TFF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92551JA" ], "uniprot_id": "Q03403" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671700" }, { "confidence": "high", "disease": "Lung transplant rejection (acute/chronic)", "glycan_involvement": "HLA-G is a glycoprotein; glycosylation may affect stability and immune recognition.", "mechanism": "HLA-G expression correlates with immunological acceptance and stable graft function; low expression or certain isoforms/haplotypes (e.g., HLA-G*01:04, HLA-G*01:06) associated with increased rejection risk.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may influence antigenicity and antibody recognition.", "mechanism": "Anti-HLA-G antibodies detected in SLE patients, suggesting immune dysregulation involving HLA-G.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "Glycosylation status may modulate HLA-G function.", "mechanism": "HLA-G*01:06~UTR2 haplotype correlated with poor clinical evolution in cystic fibrosis.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "low", "disease": "Chronic lung allograft dysfunction (CLAD)", "glycan_involvement": "Glycosylation may affect antibody binding and immune modulation.", "mechanism": "Hypothesized that anti-HLA-G antibodies may contribute to CLAD progression by interfering with immunoregulatory functions.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "causal", "source_pmcid": "PMC10671704" }, { "confidence": "low", "disease": "Pre-eclampsia", "glycan_involvement": "Glycosylation may influence HLA-G stability and immune tolerance in pregnancy.", "mechanism": "HLA-G antibodies may be more frequent in women with pregnancy complications such as pre-eclampsia.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "high", "disease": "Bronchiolitis obliterans syndrome (BOS)", "glycan_involvement": "Tubulin K-1 is a membrane glycoprotein; glycosylation may affect antigen exposure.", "mechanism": "Autoantibodies against Tubulin K-1 correlate with BOS occurrence after lung transplantation.", "protein": "Tubulin K-1", "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "high", "disease": "Bronchiolitis obliterans syndrome (BOS)", "glycan_involvement": "Collagen type V is glycosylated; glycan exposure may trigger autoimmunity.", "mechanism": "Autoantibodies against collagen type V are strongly correlated with BOS after lung transplantation.", "protein": "Collagen type V", "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "high", "disease": "Lung transplant rejection (acute/chronic)", "glycan_involvement": "Glycosylation may enhance HLA-G stability and immunosuppressive function.", "mechanism": "High membrane-bound and soluble HLA-G expression in bronchial tissue/fluids is associated with stable graft and reduced rejection.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "protective", "source_pmcid": "PMC10671704" }, { "confidence": "medium", "disease": "Viral or parasitic infection escape", "glycan_involvement": "Glycosylation may modulate HLA-G interactions with immune receptors.", "mechanism": "HLA-G expression promotes immune escape in viral/parasitic infections.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "causal", "source_pmcid": "PMC10671704" }, { "confidence": "medium", "disease": "Lung transplant rejection (acute/chronic)", "glycan_involvement": "HLA-E is glycosylated; glycan structure may affect peptide loading and immune interactions.", "mechanism": "HLA-E loads HLA-G signal peptide, indirectly influencing immune regulation and graft acceptance.", "protein": "HLA-E", "relationship_type": "biomarker", "source_pmcid": "PMC10671704" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Zonulin is glycosylated, affecting its secretion and function.", "mechanism": "Elevated zonulin antibodies indicate increased intestinal permeability, correlating with MS risk.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Occludin glycosylation modulates junction stability.", "mechanism": "Occludin antibody elevation reflects tight junction breakdown, associated with neuroinflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation influences zonulin\u2019s barrier function.", "mechanism": "Elevated zonulin antibodies linked to joint autoimmunity via gut-joint axis.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation affects occludin\u2019s localization and function.", "mechanism": "Occludin antibody elevation correlates with synovial inflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Type 1 Diabetes", "glycan_involvement": "Insulin glycosylation impacts immunogenicity.", "mechanism": "Elevated insulin autoantibodies found in subjects with increased intestinal permeability.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Autoimmune Thyroid Disease", "glycan_involvement": "Glycosylation modulates thyroglobulin antigenicity.", "mechanism": "Thyroglobulin autoantibodies elevated in subjects with leaky gut.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "medium", "disease": "Addison\u2019s Disease", "glycan_involvement": "Glycosylation may affect enzyme immunogenicity.", "mechanism": "21-hydroxylase autoantibodies increased with intestinal permeability.", "protein": "21-Hydroxylase", "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Chronic Inflammatory Bowel Diseases", "glycan_involvement": "ASCA targets glycan-rich yeast antigens.", "mechanism": "ASCA antibodies elevated in leaky gut, indicating IBD risk.", "protein": "ASCA", "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "Glycosylation affects enzyme stability and immune recognition.", "mechanism": "Autoantibodies to cytochrome P450 elevated with increased permeability.", "protein": "Cytochrome P450", "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "medium", "disease": "Gastric Autoimmunity", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "Parietal cell autoantibodies elevated in subjects with leaky gut.", "protein": "Parietal cell antigen", "relationship_type": "biomarker", "source_pmcid": "PMC10671756" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum levels and detection.", "mechanism": "AFP is produced by HCC cells and elevated in serum of HCC patients.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Fucosylation (N-glycosylation) distinguishes AFP-L3 from other AFP forms.", "mechanism": "AFP-L3 is a fucosylated glycoform of AFP produced by HCC cells; high levels indicate HCC.", "protein": "AFP-L3 (Fucosylated AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "DCP is a glycoprotein; abnormal post-translational modification (carboxylation) is key.", "mechanism": "DCP is an abnormal prothrombin variant produced by HCC cells; elevated in HCC.", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Fucosylation increases in advanced disease.", "mechanism": "AFP-L3 levels can be elevated in advanced liver disease, but higher in HCC.", "protein": "AFP-L3 (Fucosylated AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "medium", "disease": "Portal vein invasion", "glycan_involvement": "Abnormal carboxylation and glycosylation may affect DCP function.", "mechanism": "High DCP levels are associated with portal vein invasion in HCC.", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation status may affect diagnostic specificity.", "mechanism": "AFP can be elevated in cirrhosis but is higher in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Fucosylation correlates with aggressive tumor phenotype.", "mechanism": "High AFP-L3 levels are associated with increased mortality risk in HCC.", "protein": "AFP-L3 (Fucosylated AFP)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may influence AFP stability and detection.", "mechanism": "Elevated AFP is associated with higher mortality risk in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Abnormal modification impacts DCP's role as a biomarker.", "mechanism": "Elevated DCP is associated with increased mortality risk in HCC.", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Fucosylation is critical for distinguishing AFP-L3 from other AFP isoforms.", "mechanism": "AFP-L3 improves sensitivity and specificity for HCC detection when combined with AFP and DCP.", "protein": "AFP-L3 (Fucosylated AFP)", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC10671761" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "PPAR\u03b3 is glycosylated; glycosylation may affect its stability and activity, but not directly studied here.", "mechanism": "CPF exposure downregulates PPAR\u03b3, inhibiting adipocyte differentiation and altering lipid accumulation, contributing to obesity risk.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "C/EBP\u03b1 is glycosylated; glycosylation may regulate its transcriptional activity.", "mechanism": "CPF exposure downregulates C/EBP\u03b1, inhibiting adipogenesis and lipid accumulation, promoting adipocyte dysfunction and obesity.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may modulate PPAR\u03b3 function in insulin signaling.", "mechanism": "Reduced PPAR\u03b3 expression impairs insulin sensitivity and adipocyte function, increasing T2DM risk.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Potential regulatory role of glycosylation in C/EBP\u03b1 activity.", "mechanism": "Downregulation of C/EBP\u03b1 disrupts adipocyte differentiation, affecting glucose metabolism and T2DM development.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect PPAR\u03b3-mediated insulin signaling.", "mechanism": "CPF-induced reduction of PPAR\u03b3 impairs insulin sensitivity in adipocytes.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may influence C/EBP\u03b1 stability and function.", "mechanism": "Lower C/EBP\u03b1 expression impairs adipocyte function, contributing to insulin resistance.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Adipocyte hypertrophy", "glycan_involvement": "Glycosylation may modulate PPAR\u03b3's role in lipid metabolism.", "mechanism": "CPF increases fatty acid uptake in mature adipocytes, potentially via altered PPAR\u03b3 activity, leading to hypertrophy.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Adipocyte hypertrophy", "glycan_involvement": "Possible impact of glycosylation on C/EBP\u03b1 function.", "mechanism": "CPF-induced downregulation of C/EBP\u03b1 disrupts normal adipocyte differentiation, favoring hypertrophy.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "causal", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation status may affect biomarker reliability.", "mechanism": "PPAR\u03b3 expression levels reflect adipogenic activity and obesity risk under CPF exposure.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10671786" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may influence detection and function.", "mechanism": "C/EBP\u03b1 expression serves as a marker for adipocyte differentiation and obesity risk.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "biomarker", "source_pmcid": "PMC10671786" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LRG1 is a glycoprotein; glycosylation is required for its secretion and stability.", "mechanism": "LRG1 accumulates in atherosclerotic plaques, especially in calcified regions, and promotes vascular smooth muscle cell (VSMC) trans-differentiation and calcification.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "causal", "source_pmcid": "PMC10671851" }, { "confidence": "high", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation is essential for LRG1's function as a secreted signaling molecule.", "mechanism": "LRG1 directly induces VSMC calcification and osteogenic trans-differentiation via potentiation of TGF\u03b2-induced SMAD1/5 signaling.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "causal", "source_pmcid": "PMC10671851" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation enables LRG1 detection in plasma.", "mechanism": "Circulating LRG1 levels are elevated in patients with complicated atherosclerosis and localize to calcified plaque regions.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation is required for LRG1 secretion and stability in circulation.", "mechanism": "LRG1 levels are increased in plasma of diabetic patients, correlating with vascular complications.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation is necessary for LRG1's plasma presence.", "mechanism": "Elevated circulating LRG1 in CKD patients is associated with increased risk of vascular calcification and cardiovascular complications.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation supports LRG1's stability and detection.", "mechanism": "LRG1 is upregulated in plasma in various cardiovascular diseases and may reflect disease progression.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "biomarker", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "Glycosylation is required for LRG1's secretion and function.", "mechanism": "LRG1 expression in glomerular endothelial cells contributes to microvascular instability and disease progression.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "causal", "source_pmcid": "PMC10671851" }, { "confidence": "low", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation is necessary for LRG1's extracellular activity.", "mechanism": "LRG1 is increased post-infarct and may promote vascularization and cardiomyocyte survival in early phases.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "protective", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Targeting glycosylated LRG1 may affect its stability and function.", "mechanism": "LRG1 inhibition is proposed as a strategy to slow vascular calcification and plaque complications.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671851" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Therapeutic targeting may exploit glycosylation-dependent epitopes.", "mechanism": "LRG1 blockade is under evaluation for anti-angiogenic and anti-calcification effects.", "protein": "Leucine-rich alpha-2 glycoprotein 1 (LRG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10671851" }, { "confidence": "high", "disease": "Pre-eclampsia", "glycan_involvement": "SERT is a glycoprotein; glycosylation may affect its membrane localization and function, but not directly discussed.", "mechanism": "S/S genotype of 5-HTTLPR variant reduces risk of pre-eclampsia, possibly by modulating serotonin uptake and improving placental blood flow.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "protective", "source_pmcid": "PMC10671924" }, { "confidence": "high", "disease": "Pre-eclampsia with severity criteria", "glycan_involvement": "Glycosylation may influence SERT stability and activity; not directly addressed.", "mechanism": "S/S genotype associated with reduced risk of severe pre-eclampsia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "protective", "source_pmcid": "PMC10671924" }, { "confidence": "medium", "disease": "Late-onset pre-eclampsia", "glycan_involvement": "Potential impact via glycosylation on SERT function; not directly discussed.", "mechanism": "S/S genotype reduces risk of late-onset pre-eclampsia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "protective", "source_pmcid": "PMC10671924" }, { "confidence": "medium", "disease": "Intrauterine growth restriction (IUGR)", "glycan_involvement": "SERT glycosylation may affect placental localization; not directly discussed.", "mechanism": "Altered SERT function and serotonin levels may contribute to placental insufficiency and IUGR.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation could modulate SERT activity; not directly discussed.", "mechanism": "Serotonin dysregulation via SERT variants may influence maternal blood pressure.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Indirect; SERT glycosylation may affect neurodevelopmental outcomes.", "mechanism": "Intrauterine exposure to pre-eclampsia (linked to SERT variants) increases risk of autism in offspring.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "low", "disease": "Chronic kidney disease", "glycan_involvement": "Indirect; SERT glycosylation may affect systemic effects.", "mechanism": "Pre-eclampsia (influenced by SERT genotype) increases long-term risk of kidney disease.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "low", "disease": "Ischemic heart disease", "glycan_involvement": "Indirect; SERT glycosylation may affect cardiovascular outcomes.", "mechanism": "Pre-eclampsia (modulated by SERT genotype) increases risk of ischemic heart disease.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "low", "disease": "Endometriosis", "glycan_involvement": "Indirect; SERT glycosylation may affect tissue localization.", "mechanism": "Altered serotonin pathway (SERT) implicated in endometriosis and associated placental defects.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "low", "disease": "Irritable bowel syndrome", "glycan_involvement": "Indirect; SERT glycosylation may affect GI tract function.", "mechanism": "Serotonin pathway alterations (SERT) linked to IBS, which is associated with pre-eclampsia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC10671924" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "\u03b22 glycoprotein I is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Elevated titres and prevalence in cancer patients; best predictor among tested aPLs.", "protein": "Anti-\u03b22 glycoprotein I antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "high", "disease": "Gastrointestinal cancer", "glycan_involvement": "Antibody targets phospholipid-protein complexes; glycosylation may modulate immune response.", "mechanism": "Significantly higher positivity and titres in GI cancer; best predictor for GI cancer.", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Gastrointestinal cancer", "glycan_involvement": "Targets phospholipid-protein complexes; glycosylation may influence antigen presentation.", "mechanism": "Higher titres in GI cancer; second best predictor for GI cancer.", "protein": "Anti-phosphatidylserine antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation of \u03b22GPI affects antibody binding and pathogenicity.", "mechanism": "Associated with increased risk of thrombosis in cancer, but not observed in this cohort.", "protein": "Anti-\u03b22 glycoprotein I antibody", "relationship_type": "causal (potential)", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation of target proteins may affect immune complex formation.", "mechanism": "Linked to increased thrombosis risk in cancer, but not confirmed in this study.", "protein": "Anti-cardiolipin antibody", "relationship_type": "causal (potential)", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Targets phospholipid-protein complexes; glycosylation may modulate immune recognition.", "mechanism": "Elevated titres in cancer patients; potential diagnostic value.", "protein": "Anti-phosphatidylethanolamine antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Prothrombin is glycosylated; glycan structures may affect antigenicity.", "mechanism": "Higher prevalence in cancer patients; possible role in thrombosis risk.", "protein": "Anti-prothrombin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "medium", "disease": "Uterine cancer", "glycan_involvement": "Glycosylation may influence immune response to phospholipid-protein complexes.", "mechanism": "Non-criteria aPLs more frequent in uterine cancer than non-malignant gynecologic disease.", "protein": "Anti-phosphatidylserine antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "N-glycosylation modulates \u03b22GPI structure and antibody binding.", "mechanism": "Target antigen for aPLs in APS; glycosylation affects antigenicity and immune response.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC10671946" }, { "confidence": "low", "disease": "Pulmonary cancer", "glycan_involvement": "Glycosylation may affect immune complex formation.", "mechanism": "Previously reported association with pulmonary cancer (not confirmed in this study).", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10671946" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation affects receptor expression and function on platelets.", "mechanism": "P2Y12 receptor mediates ADP-induced platelet aggregation; inhibition reduces thrombosis risk.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672070" }, { "confidence": "high", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Inhibition prevents platelet aggregation on stent surfaces.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672070" }, { "confidence": "high", "disease": "Myocardial infarction (MI)", "glycan_involvement": "N-glycosylation required for surface expression and ligand binding.", "mechanism": "Mediates final common pathway of platelet aggregation; blockade reduces MI risk.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Aspirin inhibits COX-1, reducing thromboxane A2 and platelet activation.", "protein": "Cyclooxygenase-1 (COX-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Bleeding complications", "glycan_involvement": "N-glycosylation critical for function and clearance.", "mechanism": "Essential for platelet adhesion; deficiency increases bleeding risk.", "protein": "Von Willebrand Factor", "relationship_type": "causal", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation affects solubility and receptor binding.", "mechanism": "Bridges platelets via GPIIb/IIIa; essential for thrombus formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "Glycosylation required for cell adhesion function.", "mechanism": "Platelet activation marker; elevated in PAD.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation essential for vWF binding.", "mechanism": "Mediates platelet adhesion to damaged endothelium; contributes to thrombus formation.", "protein": "Glycoprotein Ib (GPIb)", "relationship_type": "causal", "source_pmcid": "PMC10672070" }, { "confidence": "low", "disease": "Restenosis", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Collagen receptor; mediates platelet activation after vascular injury.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC10672070" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may alter receptor sensitivity.", "mechanism": "Enhanced ADP-induced platelet activation in diabetes; P2Y12 inhibitors reduce risk.", "protein": "ADP receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672070" }, { "confidence": "high", "disease": "Chemotherapy resistance", "glycan_involvement": "P-gp is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Dexamethasone induces P-gp expression, increasing drug efflux and reducing intracellular drug concentrations.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "high", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "CYP3A4 is not a glycoprotein; no direct glycan involvement.", "mechanism": "Dexamethasone induces CYP3A4, increasing metabolism of drugs like lapatinib, leading to toxic metabolites and hepatotoxicity.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "high", "disease": "Reduced efficacy of ivermectin", "glycan_involvement": "P-gp glycosylation required for function.", "mechanism": "Dexamethasone induces P-gp, increasing ivermectin efflux and reducing its plasma concentration and efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "medium", "disease": "Altered fetal drug exposure", "glycan_involvement": "Placental P-gp glycosylation critical for barrier function.", "mechanism": "Dexamethasone induces placental P-gp, reducing fetal exposure to P-gp substrate drugs.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "protective/causal", "source_pmcid": "PMC10672071" }, { "confidence": "medium", "disease": "Altered fetal drug exposure", "glycan_involvement": "BCRP is glycosylated; glycosylation affects transporter activity.", "mechanism": "Dexamethasone inhibits placental BCRP, increasing fetal exposure to BCRP substrate drugs.", "protein": "BCRP", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "medium", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "MRP3 glycosylation required for function.", "mechanism": "Dexamethasone induces MRP3, altering hepatic drug efflux and potentially contributing to hepatotoxicity.", "protein": "MRP3", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "low", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "OATP1A4 is glycosylated; glycosylation affects substrate recognition.", "mechanism": "Dexamethasone may induce OATP1A4, increasing hepatic uptake of drugs and risk of toxicity.", "protein": "OATP1A4", "protein_enriched": { "function": "Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at ", "gene_name": "SLCO1C1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NYB5" }, "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "P-gp glycosylation modulates drug response.", "mechanism": "Dexamethasone is used in combination chemotherapy; P-gp induction may affect drug efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672071" }, { "confidence": "high", "disease": "Voriconazole treatment failure", "glycan_involvement": "P-gp glycosylation required for transporter function.", "mechanism": "Dexamethasone induces P-gp and CYPs, increasing voriconazole clearance and reducing efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "medium", "disease": "Phenytoin-induced thrombopenia", "glycan_involvement": "P-gp glycosylation required for function.", "mechanism": "Dexamethasone induces CYP2C9/19 and possibly P-gp, increasing phenytoin metabolism and risk of adverse effects.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC10672071" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "VWF is a heavily glycosylated protein; glycosylation affects multimer formation and function.", "mechanism": "Elevated plasma VWF reflects endothelial activation/damage and predicts mortality.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and 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"G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ADAMTS13 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Reduced ADAMTS13 activity/antigen is associated with severe/critical COVID-19 and coagulopathy.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Both proteins are glycosylated; ratio reflects imbalance in glycoprotein-mediated hemostasis.", "mechanism": "Elevated VWF/ADAMTS13 ratio predicts increased mortality and adverse outcomes.", "protein": "VWF/ADAMTS13 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation regulates VWF multimer size and platelet binding.", "mechanism": "High VWF promotes platelet aggregation and microvascular thrombosis.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC10672082" }, { "confidence": "high", "disease": "Thrombotic thrombocytopenic purpura (TTP)", "glycan_involvement": "Glycosylation affects ADAMTS13 secretion and activity.", "mechanism": "Severe ADAMTS13 deficiency leads to accumulation of ULVWF and microthrombi.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "causal", "source_pmcid": "PMC10672082" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation modulates ADAMTS13 function.", "mechanism": "Mild/moderate reduction in ADAMTS13 increases risk of stroke via impaired VWF cleavage.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "protective", "source_pmcid": "PMC10672082" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation influences ADAMTS13 stability and activity.", "mechanism": "Reduced ADAMTS13 activity predisposes to coronary thrombosis.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "protective", "source_pmcid": "PMC10672082" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects ADAMTS13 levels in plasma.", "mechanism": "Lower ADAMTS13 activity associated with pregnancy complications.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Syndecan-1 is a proteoglycan; glycosaminoglycan chains are shed during injury.", "mechanism": "Shedding of syndecan-1 indicates endothelial glycocalyx degradation in COVID-19.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Thrombomodulin is glycosylated; glycosylation affects its anticoagulant function.", "mechanism": "Elevated plasma thrombomodulin reflects endothelial injury.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672082" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated ALP is a diagnostic marker for cholestasis in PBC.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "GGT is a glycoprotein; glycosylation modulates its secretion.", "mechanism": "Elevated GGT is used as a biochemical criterion for PBC diagnosis.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "IgG glycosylation modulates immune activity and autoimmunity.", "mechanism": "Elevated IgG is a diagnostic criterion for AIH and VS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "AMA-M2 targets mitochondrial glycoproteins; glycosylation may affect antigenicity.", "mechanism": "AMA-M2 is highly specific for PBC and used for diagnosis.", "protein": "Antimitochondrial antibody M2 (AMA-M2)", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "gp210 is a nuclear pore glycoprotein; glycosylation may affect epitope exposure.", "mechanism": "Anti-gp210 autoantibodies are associated with PBC and may indicate prognosis.", "protein": "Anti-gp210", "protein_enriched": { "function": "Nucleoporin essential for nuclear pore assembly and fusion, nuclear pore spacing, as well as structural integrity", "gene_name": "NUP210", "glycan_count": 23, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G41247ZX", "G62765YT", "G80920RR", "G89377PF", "G49108TO", "G05724UK", "G06110VR", "G31852PQ", "G39188ZX", "G64527OM", "G70101JE", "G72747WU", "G15664MX", "G25079LO", "G46503DX", "G62894KT", "G02815KT", "G23984SE", "G36379GD", "G83460ZZ", "G92050GC", "G92275SC", "G93718GY" ], "uniprot_id": "Q8TEM1" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Sp100 is a nuclear body glycoprotein; glycosylation may influence antigenicity.", "mechanism": "Anti-Sp100 autoantibodies are associated with PBC and VS.", "protein": "Anti-Sp100", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "medium", "disease": "PBC-AIH Variant Syndrome (VS)", "glycan_involvement": "CENP-A is a centromere glycoprotein; glycosylation may affect immune recognition.", "mechanism": "Anti-CENP-A autoantibodies are frequently detected in VS and may aid diagnosis.", "protein": "Anti-centromere protein A (CENP-A)", "protein_enriched": { "function": "Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:11756469, PubMed:14667408, PubMed:15282608, PubMed:15475964, PubMed:15702419, PubMed:17651496, PubMed:", "gene_name": "CENPA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49450" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "medium", "disease": "PBC-AIH Variant Syndrome (VS)", "glycan_involvement": "CENP-B is a centromere glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-CENP-B autoantibodies are detected in VS and may support diagnosis.", "protein": "Anti-centromere protein B (CENP-B)", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "ANAs target various nuclear glycoproteins; glycosylation may modulate immune response.", "mechanism": "ANA positivity is a serological criterion for AIH and VS.", "protein": "Anti-nuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "SMAs target actin and related glycoproteins; glycosylation may influence antigenicity.", "mechanism": "Anti-SMA is a diagnostic marker for AIH and VS.", "protein": "Anti-smooth muscle antibody (SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC10672247" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "vWF is heavily glycosylated; glycosylation affects multimerization and function.", "mechanism": "vWF deficiency or dysfunction causes bleeding; DDAVP increases vWF release via V2 receptor activation.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Factor VIII is glycosylated; glycosylation affects stability and activity.", "mechanism": "Factor VIII deficiency causes bleeding; DDAVP increases plasma Factor VIII via V2 receptor activation.", "protein": "Factor VIII", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Copeptin is a glycoprotein fragment; glycosylation increases plasma stability.", "mechanism": "Copeptin levels correlate with AVP levels and may guide AVP therapy in septic shock.", "protein": "Copeptin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672256" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "LNPEP is glycosylated; glycosylation affects enzyme stability and activity.", "mechanism": "Genetic variation in LNPEP increases AVP clearance, affecting vasopressor response and mortality.", "protein": "Leucyl and cystinyl aminopeptidase (LNPEP/vasopressinase)", "protein_enriched": { "function": "Mitochondrial protein required for adaptation of miochondrial dynamics to metabolic changes. Regulates mitochondrial morphology at steady state and mediates AMPK-dependent stress-induced mitochondrial", "gene_name": "MTFR1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H019" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10672256" }, { "confidence": "high", "disease": "Congenital or acquired platelet disorders", "glycan_involvement": "Glycosylation of vWF is essential for platelet binding and function.", "mechanism": "DDAVP increases vWF release, improving hemostasis in platelet disorders.", "protein": "von Willebrand factor (vWF)", "relationship_type": "therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Glycosylation affects Factor VIII stability and interaction with vWF.", "mechanism": "DDAVP increases Factor VIII and vWF, improving clotting in mild vWD.", "protein": "Factor VIII", "relationship_type": "therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation increases copeptin stability in plasma.", "mechanism": "Copeptin is chronically elevated in heart failure, reflecting AVP system activation.", "protein": "Copeptin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672256" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Glycosylation regulates vWF multimer size and function.", "mechanism": "AVP/DDAVP-induced vWF release may support hemostasis during septic shock.", "protein": "von Willebrand factor (vWF)", "relationship_type": "protective/therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Glycosylation affects Factor VIII stability and activity.", "mechanism": "AVP/DDAVP-induced Factor VIII release may support coagulation during septic shock.", "protein": "Factor VIII", "relationship_type": "protective/therapeutic target", "source_pmcid": "PMC10672256" }, { "confidence": "low", "disease": "Diabetes insipidus", "glycan_involvement": "Glycosylation modulates LNPEP activity and plasma half-life.", "mechanism": "LNPEP degrades AVP; increased activity may contribute to AVP deficiency.", "protein": "Leucyl and cystinyl aminopeptidase (LNPEP/vasopressinase)", "protein_enriched": { "function": "Mitochondrial protein required for adaptation of miochondrial dynamics to metabolic changes. Regulates mitochondrial morphology at steady state and mediates AMPK-dependent stress-induced mitochondrial", "gene_name": "MTFR1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H019" }, "relationship_type": "causal", "source_pmcid": "PMC10672256" }, { "confidence": "high", "disease": "Low-grade systemic inflammation", "glycan_involvement": "IL-1ra is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "IL-1ra antagonizes IL-1RI, suppressing pro-inflammatory signaling and reducing systemic inflammation.", "protein": "IL-1ra", "relationship_type": "protective", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation supports IL-1ra's stability and bioactivity.", "mechanism": "Exercise-induced IL-1ra may contribute to anti-inflammatory effects, protecting against cardiovascular complications.", "protein": "IL-1ra", "relationship_type": "protective", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation may influence IL-1ra's half-life and receptor binding.", "mechanism": "IL-1ra improves blood glucose levels and suppresses inflammation, reducing diabetes risk.", "protein": "IL-1ra", "relationship_type": "protective", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Heart failure (acute hypertension)", "glycan_involvement": "Glycosylation required for proper secretion and function.", "mechanism": "IL-1ra prevents progression to heart failure by suppressing systemic inflammation.", "protein": "IL-1ra", "relationship_type": "protective", "source_pmcid": "PMC10672277" }, { "confidence": "high", "disease": "Acute and chronic inflammation", "glycan_involvement": "Heavily glycosylated; glycosylation is essential for ligand binding and receptor function.", "mechanism": "IL-1RI mediates IL-1\u03b1/\u03b2 signaling, driving inflammatory responses.", "protein": "IL-1RI", "relationship_type": "causal", "source_pmcid": "PMC10672277" }, { "confidence": "high", "disease": "Low-grade systemic inflammation", "glycan_involvement": "IL-6 is glycosylated, which may affect secretion and receptor interaction.", "mechanism": "Elevated IL-6 reflects chronic inflammation and is increased after strenuous exercise.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "Glycosylation impacts pharmacokinetics and efficacy.", "mechanism": "IL-1ra blocks IL-1RI, reducing autoimmune-driven inflammation.", "protein": "IL-1ra", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Infections", "glycan_involvement": "Glycosylation may affect circulating levels.", "mechanism": "IL-1ra levels rise in response to infection-induced inflammation.", "protein": "IL-1ra", "relationship_type": "biomarker", "source_pmcid": "PMC10672277" }, { "confidence": "medium", "disease": "Trauma", "glycan_involvement": "Glycosylation supports stability and secretion.", "mechanism": "IL-1ra is upregulated after trauma as part of the anti-inflammatory response.", "protein": "IL-1ra", "relationship_type": "biomarker", "source_pmcid": "PMC10672277" }, { "confidence": "high", "disease": "Spinal cord injury (SCI/CSCI)", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "Exercise increases IL-1ra in SCI/CSCI, indicating anti-inflammatory adaptation.", "protein": "IL-1ra", "relationship_type": "biomarker", "source_pmcid": "PMC10672277" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its metabolism and clearance.", "mechanism": "Elevated LDL levels are associated with H. pylori infection, indicating dyslipidemia.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC10672336" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "HDL is a glycoprotein; glycosylation modulates its anti-atherogenic function.", "mechanism": "Decreased HDL levels are associated with H. pylori infection, indicating dyslipidemia.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of LDL influences its uptake by macrophages and plaque formation.", "mechanism": "Elevated LDL in H. pylori-infected individuals increases atherosclerosis risk.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "HDL glycosylation is critical for cholesterol efflux and anti-inflammatory properties.", "mechanism": "Reduced HDL in H. pylori infection removes protective effect against atherosclerosis.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Coronary heart disease", "glycan_involvement": "Altered glycosylation may enhance LDL atherogenicity.", "mechanism": "High LDL due to H. pylori infection is a risk factor for coronary heart disease.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Coronary heart disease", "glycan_involvement": "Glycosylation affects HDL's anti-atherogenic function.", "mechanism": "Low HDL in H. pylori infection increases coronary heart disease risk.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Bacterial glycoproteins may mimic host glycans, affecting immune response and lipid metabolism.", "mechanism": "H. pylori infection triggers inflammation and metabolic changes leading to dyslipidemia.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "high", "disease": "Chronic gastritis", "glycan_involvement": "Bacterial glycoproteins interact with gastric mucosal glycans.", "mechanism": "H. pylori colonization causes chronic gastritis.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Molecular mimicry of glycan structures may contribute to oncogenesis.", "mechanism": "Chronic H. pylori infection increases risk of gastric carcinogenesis.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "high", "disease": "Peptic ulcer", "glycan_involvement": "Glycoprotein-mediated adhesion to gastric mucosa is critical.", "mechanism": "H. pylori infection leads to mucosal damage and ulcer formation.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC10672336" }, { "confidence": "high", "disease": "Pleural Mesothelioma", "glycan_involvement": "Fibulin-3 is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Overexpressed in PM; promotes malignant behavior, cell proliferation, migration, and chemoresistance.", "protein": "Fibulin-3", "protein_enriched": { "function": "Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulato", "gene_name": "EFEMP1", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27391WQ", "G43417UB", "G53434XO", "G57317CE", "G29068FM", "G57321FI", "G71142DF", "G49108TO" ], "uniprot_id": "Q12805" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10672377" }, { "confidence": "high", "disease": "Pleural Mesothelioma", "glycan_involvement": "Mesothelin is glycosylated; glycosylation may affect cell adhesion and immunogenicity.", "mechanism": "Overexpressed in epithelioid PM; used for diagnosis, prognosis, and as a therapeutic target.", "protein": "Mesothelin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "CEA is heavily glycosylated; glycosylation affects cell adhesion and biomarker detection.", "mechanism": "CEA levels are increased in PM but less than in other cancers; high CEA may exclude PM.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "high", "disease": "Pleural Mesothelioma", "glycan_involvement": "Osteopontin is glycosylated; glycosylation may influence its stability and function.", "mechanism": "Elevated in PM; high levels correlate with poor prognosis.", "protein": "Osteopontin", "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation mediates galectin binding and immune modulation.", "mechanism": "Identified in proteomic panels as a diagnostic marker for PM.", "protein": "Galectin-3 binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation may affect extracellular matrix interactions.", "mechanism": "Part of diagnostic protein panels distinguishing PM from non-PM.", "protein": "Testican-2", "protein_enriched": { "function": "May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles", "gene_name": "APOL6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BWW8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Glycosylation affects immune function and biomarker detection.", "mechanism": "Included in proteomic panels for PM diagnosis.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Heparan sulfate glycosylation modulates cell signaling and adhesion.", "mechanism": "Associated with PM in pleural effusion biomarker panels.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Fragment may retain glycosylation affecting detection.", "mechanism": "Elevated in PM; reflects tumor cell necrosis/apoptosis.", "protein": "CYFRA-21-1 (Cytokeratin 19 fragment)", "relationship_type": "biomarker", "source_pmcid": "PMC10672377" }, { "confidence": "medium", "disease": "Pleural Mesothelioma", "glycan_involvement": "Calretinin is glycosylated; glycosylation may affect cell proliferation and migration.", "mechanism": "Overexpressed in PM; used for diagnosis and as a potential therapeutic target.", "protein": "Calretinin", "protein_enriched": { "function": "Calcium-binding protein involved in calcium homeostasis and signal transduction. It plays a critical role in buffering intracellular calcium levels and modulating calcium-dependent signaling pathways ", "gene_name": "CALB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22676" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10672377" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HANDs)", "glycan_involvement": "gp120 is heavily glycosylated; glycosylation shields it from immune recognition and mediates cell entry.", "mechanism": "gp120 is released by HIV-infected cells, taken up by neurons, causing axonal damage, impaired neurogenesis, apoptosis, and synaptic dysfunction.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp41 is glycosylated, affecting fusion and immune evasion.", "mechanism": "gp41 mediates viral fusion with host cells; targeted by fusion inhibitors to block HIV entry.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HANDs)", "glycan_involvement": "LIF is a glycoprotein; glycosylation required for secretion and receptor binding.", "mechanism": "LIF promotes neurogenesis, neural cell differentiation, and survival; counteracts neurotoxic effects of HIV proteins via JAK/STAT3 pathway.", "protein": "Leukemia Inhibitory Factor (LIF)", "protein_enriched": { "function": "LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of ", "gene_name": "LIF", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P15018" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HANDs)", "glycan_involvement": "NFL is glycosylated; glycosylation may affect stability and detection.", "mechanism": "Elevated NFL levels in CSF and blood correlate with neuronal injury and progression of HANDs.", "protein": "Neurofilament Light Chain (NFL)", "relationship_type": "biomarker", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CCR5 is glycosylated; glycosylation modulates receptor function and HIV binding.", "mechanism": "CCR5 is a co-receptor for HIV entry; antagonists (e.g., Maraviroc) block HIV infection and reduce neuroinflammation.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CD4 is glycosylated; glycosylation affects HIV binding and immune function.", "mechanism": "CD4 is the primary receptor for HIV entry; targeted by post-attachment inhibitors.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672511" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HANDs)", "glycan_involvement": "STAT3 is glycosylated; glycosylation may affect signaling.", "mechanism": "STAT3 activation by LIF promotes neuroprotection and limits HIV replication; HIV proteins inhibit STAT3 to evade immune response.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC10672511" }, { "confidence": "medium", "disease": "HIV-associated dementia (HAD)", "glycan_involvement": "P-glycoprotein is glycosylated; glycosylation affects transporter function and drug efflux.", "mechanism": "Overexpression in BBB limits ART penetration, contributing to neurocognitive impairment.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10672511" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive disorders (HANDs)", "glycan_involvement": "Tat interacts with glycoproteins; glycosylation may affect uptake and toxicity.", "mechanism": "Tat released by HIV-infected cells induces dendritic loss and neuronal dysfunction.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC10672511" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "LIF glycosylation required for activity and neuroprotection.", "mechanism": "LIF reduces retinal ganglion cell loss and apoptosis via STAT3/mTOR signaling.", "protein": "Leukemia Inhibitory Factor (LIF)", "protein_enriched": { "function": "LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of ", "gene_name": "LIF", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P15018" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC10672511" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Fibrinogen is a glycoprotein; glycosylation affects solubility and function.", "mechanism": "Elevated fibrinogen increases fibrin network, clot rigidity, and resistance to fibrinolysis, raising thrombosis risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC10672518" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Plasminogen is N-glycosylated, affecting activation and fibrin binding.", "mechanism": "Plasminogen is converted to plasmin, which degrades fibrin clots; impaired activation leads to thrombosis.", "protein": "Plasminogen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672518" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "N- and O-glycosylation (Asn-11, Thr-61, Asn-448) modulate receptor binding and activity.", "mechanism": "t-PA activates plasminogen to plasmin, dissolving clots in acute MI.", "protein": "Tissue-type plasminogen activator (t-PA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672518" }, { "confidence": "medium", "disease": "Cancer (Leukaemia)", "glycan_involvement": "Highly glycosylated; glycosylation regulates cell surface localization and ligand binding.", "mechanism": "u-PAR is overexpressed in tumor and immune cells, enhancing plasminogen activation and cell migration.", "protein": "Urokinase plasminogen activator receptor (u-PAR)", "relationship_type": "biomarker", "source_pmcid": "PMC10672518" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation affects plasma half-life and inhibitory function.", "mechanism": "Inhibits plasmin, stabilizing fibrin clots and increasing thrombosis risk when elevated.", "protein": "\u03b12-antiplasmin", "relationship_type": "causal", "source_pmcid": "PMC10672518" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation stabilizes PAI-1 structure and function.", "mechanism": "Elevated PAI-1 inhibits t-PA/u-PA, reducing fibrinolysis and promoting atherothrombosis.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672518" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation modulates fibrinogen's plasma stability and clot properties.", "mechanism": "High plasma fibrinogen correlates with increased stroke risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672518" }, { "confidence": "medium", "disease": "Renal failure", "glycan_involvement": "Glycosylation affects plasminogen activation and clearance.", "mechanism": "Hyperfibrinolysis (excess plasmin activity) is seen in renal failure, leading to bleeding.", "protein": "Plasminogen", "relationship_type": "biomarker", "source_pmcid": "PMC10672518" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation influences t-PA's plasma half-life and receptor interactions.", "mechanism": "Reduced t-PA activity contributes to hypofibrinolysis and increased thrombosis risk in diabetes.", "protein": "Tissue-type plasminogen activator (t-PA)", "relationship_type": "biomarker", "source_pmcid": "PMC10672518" }, { "confidence": "medium", "disease": "Menorrhagia", "glycan_involvement": "Glycosylation impacts inhibitory activity and plasma stability.", "mechanism": "Deficiency or dysfunction leads to hyperfibrinolysis and excessive menstrual bleeding.", "protein": "\u03b12-antiplasmin", "relationship_type": "biomarker", "source_pmcid": "PMC10672518" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "SPARC is a glycoprotein; glycosylation may affect its extracellular matrix interactions.", "mechanism": "SPARC overexpression (from obesity) may protect bone mineral density in CKD via calcium- and collagen-binding, enhancing bone structure.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "protective", "source_pmcid": "PMC10672555" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation may regulate SPARC secretion and stability.", "mechanism": "SPARC levels increase with obesity, produced by adipose tissue and muscle; correlates with BMI and fat percentage.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "biomarker", "source_pmcid": "PMC10672555" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation may modulate SPARC\u2019s bone matrix binding.", "mechanism": "SPARC strengthens bone via mineralized collagen formation; deficiency leads to osteopenia and reduced bone formation.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "protective", "source_pmcid": "PMC10672555" }, { "confidence": "medium", "disease": "Vascular Calcification", "glycan_involvement": "Glycosylation may influence SPARC\u2019s calcification activity.", "mechanism": "SPARC\u2019s calcium- and collagen-binding properties may promote vascular calcification, especially in CKD and obesity.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "causal", "source_pmcid": "PMC10672555" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect SPARC\u2019s circulating levels.", "mechanism": "SPARC plasma levels correlate with BMI and fat percentage in newly diagnosed T2DM patients.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "biomarker", "source_pmcid": "PMC10672555" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may modulate SPARC\u2019s anti-cancer activity.", "mechanism": "SPARC has cancer-inhibitory properties; overexpression may suppress tumorigenesis.", "protein": "SPARC (Secreted Protein Acidic and Rich in Cysteine)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672555" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Osteopontin is highly phosphorylated and glycosylated; modifications affect cell adhesion and mineralization.", "mechanism": "CKD increases circulating and kidney osteopontin levels; may contribute to bone protection when combined with obesity-induced overexpression.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC10672555" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation and phosphorylation regulate osteopontin\u2019s function.", "mechanism": "Osteopontin levels increase with obesity and decrease with exercise-induced fat loss.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC10672555" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation/phosphorylation modulate osteopontin\u2019s bone matrix interactions.", "mechanism": "Osteopontin regulates bone cell differentiation, adhesion, and mineralization, contributing to bone homeostasis.", "protein": "Osteopontin", "relationship_type": "protective", "source_pmcid": "PMC10672555" }, { "confidence": "medium", "disease": "Vascular Calcification", "glycan_involvement": "Glycosylation/phosphorylation affect osteopontin\u2019s calcification activity.", "mechanism": "Acute osteopontin increase ameliorates vascular calcification; chronic increase worsens cardiovascular outcomes.", "protein": "Osteopontin", "relationship_type": "causal", "source_pmcid": "PMC10672555" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and trafficking.", "mechanism": "APP is cleaved to produce A\u03b2, which aggregates to form plaques, a hallmark of AD.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC10672606" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation state may affect aggregation.", "mechanism": "A\u03b2 aggregates form extracellular plaques, driving neurodegeneration.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10672606" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Tau is a glycoprotein; glycosylation may modulate aggregation and phosphorylation.", "mechanism": "Hyperphosphorylated Tau forms neurofibrillary tangles, contributing to neuronal dysfunction.", "protein": "Tau protein", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10672606" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "PSEN1 is glycosylated; glycosylation may affect \u03b3-secretase activity.", "mechanism": "PSEN1 is part of \u03b3-secretase complex that cleaves APP, influencing A\u03b2 production.", "protein": "Presenilin 1 (PSEN1)", "relationship_type": "causal", "source_pmcid": "PMC10672606" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "PSEN2 is glycosylated; glycosylation may modulate function.", "mechanism": "PSEN2 mutations alter \u03b3-secretase activity, affecting A\u03b2 generation.", "protein": "Presenilin 2 (PSEN2)", "relationship_type": "causal", "source_pmcid": "PMC10672606" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "ApoE4 is glycosylated; glycosylation influences lipid and A\u03b2 binding.", "mechanism": "ApoE4 allele increases risk of AD by affecting A\u03b2 clearance.", "protein": "Apolipoprotein E4 (ApoE4)", "relationship_type": "risk factor", "source_pmcid": "PMC10672606" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "NCT is highly N-glycosylated, essential for \u03b3-secretase function.", "mechanism": "NCT is a \u03b3-secretase subunit required for APP cleavage.", "protein": "Nicastrin (NCT)", "protein_enriched": { "function": "Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precurso", "gene_name": "NCSTN", "glycan_count": 31, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G25079LO", "G28681TP", "G37509XX", "G62765YT", "G80920RR", "G90382BL", "G05724UK", "G28541PG", "G64527OM", "G70101JE", "G57317CE", "G71195LR", "G84349RE", "G14260UH", "G31852PQ", "G41247ZX", "G49108TO", "G83633GK", "G43769HG", "G83460ZZ", "G02815KT", "G39188ZX", "G92275SC", "G08290VR", "G05049YU", "G15664MX", "G23505EP", "G72747WU", "G90659AW", "G96326PH", "G37692EO" ], "uniprot_id": "Q92542" }, "relationship_type": "causal", "source_pmcid": "PMC10672606" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Gingipains are bacterial glycoproteins; their glycosylation may affect host interactions.", "mechanism": "Gingipains hydrolyze Tau protein, exacerbate Tau hyperphosphorylation, and promote neuroinflammation.", "protein": "Porphyromonas gingivalis gingipains (Kgp, RgpA, RgpB)", "relationship_type": "causal", "source_pmcid": "PMC10672606" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Glycosylation of APP may modulate susceptibility to altered processing.", "mechanism": "Periodontitis (via P. gingivalis) increases APP processing and A\u03b2 deposition in the brain.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "indirect/causal", "source_pmcid": "PMC10672606" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "A\u03b2 glycosylation state may influence aggregation in inflammatory conditions.", "mechanism": "Periodontitis increases neuroinflammation, leading to increased A\u03b2 deposition.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "indirect/biomarker", "source_pmcid": "PMC10672606" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry via ACE2 binding; mutations increase infectivity and transmissibility.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "Vaccine escape", "glycan_involvement": "Glycosylation shields epitopes from antibody recognition.", "mechanism": "Mutations (e.g., E484K, N501Y, \u0394H69/V70) reduce neutralizing antibody binding, enabling immune escape.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672769" }, { "confidence": "medium", "disease": "Antiviral resistance", "glycan_involvement": "Glycosylation may affect drug accessibility.", "mechanism": "Mutations (e.g., T1117I, A262S) alter drug binding sites, affecting antiviral efficacy.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "Reinfection", "glycan_involvement": "Glycan shield contributes to immune evasion.", "mechanism": "Mutational changes allow escape from prior immunity, leading to reinfection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672769" }, { "confidence": "medium", "disease": "Diagnostic failure", "glycan_involvement": "Glycosylation may alter epitope presentation.", "mechanism": "Mutations (e.g., S180I, A220V) in N protein can affect antigen test sensitivity.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "Antiviral resistance", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "G15S mutation confers reduced susceptibility to protease inhibitors (nirmatrelvir, ensitrelvir).", "protein": "3CLpro (Main protease, nsp5)", "protein_enriched": { "function": "Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672769" }, { "confidence": "medium", "disease": "Antiviral resistance", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "Unusual mutations (A1803V, D1809N, A949T) may affect drug binding and resistance.", "protein": "PLpro (Papain-like protease, nsp3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "Antiviral resistance", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "P323L mutation does not confer resistance to polymerase inhibitors (e.g., remdesivir).", "protein": "RdRp (RNA-dependent RNA polymerase, nsp12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns may affect sequencing accuracy.", "mechanism": "Partial spike sequencing accurately identifies circulating variants.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672769" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "High mutation rate in N protein impacts pathogenesis and diagnostic assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672769" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects its stability and receptor binding.", "mechanism": "TNF-\u03b1 induces mtROS production in hepatocytes, leading to mitochondrial dysfunction and lipid accumulation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672841" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "TNFR1 glycosylation modulates ligand binding and signaling.", "mechanism": "TNF-\u03b1 binds TNFR1 on hepatocytes, triggering mtROS generation and promoting steatosis.", "protein": "TNFR1", "relationship_type": "causal", "source_pmcid": "PMC10672841" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "NF-\u03baB activation is modulated by upstream glycoprotein receptors.", "mechanism": "mtROS-mediated activation of NF-\u03baB in Kupffer cells drives inflammation and progression of NAFLD.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "Elevated IL-1\u03b2 mRNA in Kupffer cells correlates with inflammation in NAFLD.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Ccl2 glycosylation modulates chemotactic activity.", "mechanism": "Ccl2 upregulation in Kupffer cells is associated with hepatic inflammation and lipid accumulation.", "protein": "Ccl2", "relationship_type": "biomarker", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Ccl3 glycosylation influences receptor interaction.", "mechanism": "Ccl3 expression increases during Kupffer cell activation in NAFLD.", "protein": "Ccl3", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependen", "gene_name": "Ccl3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10855" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "Cxcl2 is upregulated in inflammatory response in NAFLD.", "protein": "Cxcl2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41754" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates chemokine stability.", "mechanism": "Cxcl9 elevation marks Kupffer cell-driven inflammation in NAFLD.", "protein": "Cxcl9", "protein_enriched": { "function": "Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released (PubMed:19812333). After synthesis, participates in the for", "gene_name": "Pclo", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q9QYX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "SOD1 glycosylation may affect cellular localization and activity.", "mechanism": "SOD1 preserves antioxidant defense in Kupffer cells, reducing mtROS and inflammation.", "protein": "SOD1", "relationship_type": "protective", "source_pmcid": "PMC10672841" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences TNF-\u03b1 stability and fibrogenic signaling.", "mechanism": "Chronic TNF-\u03b1 signaling promotes progression from NAFLD to liver fibrosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10672841" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "CRP is a glycoprotein; its glycosylation is essential for stability and function.", "mechanism": "Low CRP levels are predictive for SFTS compared to rickettsiosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10672843" }, { "confidence": "high", "disease": "Japanese spotted fever (JSF)", "glycan_involvement": "Glycosylation affects CRP's serum half-life and immune interactions.", "mechanism": "Elevated CRP levels are typical in JSF, distinguishing it from SFTS.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10672843" }, { "confidence": "high", "disease": "Scrub typhus (ST)", "glycan_involvement": "Glycosylation affects CRP's serum half-life and immune interactions.", "mechanism": "Elevated CRP levels are typical in ST, distinguishing it from SFTS.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10672843" }, { "confidence": "medium", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Glycosylation of viral glycoproteins is critical for infectivity and immune escape.", "mechanism": "Viral envelope glycoproteins mediate host cell entry and immune evasion.", "protein": "Dabie bandavirus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10672843" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "EGFR is a glycoprotein; altered glycosylation may affect ligand binding and signaling.", "mechanism": "EGFR is upregulated in BL2 TNBC subtype, promoting growth factor signaling and tumor progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "HER2 is a glycoprotein; loss of HER2 glycosylation is part of TNBC definition.", "mechanism": "TNBC is defined by absence of HER2 expression; HER2 is a key diagnostic marker.", "protein": "HER2 (ERBB2)", "relationship_type": "biomarker", "source_pmcid": "PMC10672974" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "MET is a glycoprotein; glycosylation may regulate receptor stability and signaling.", "mechanism": "MET is upregulated in BL2 TNBC subtype, contributing to tumor growth and metastasis.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "PARP1 is glycosylated; glycosylation may affect nuclear localization and function.", "mechanism": "PARP1 is targeted by PARP inhibitors to exploit DNA repair defects in BRCA-mutant TNBC.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "BRCA1 may be glycosylated; impact on DNA repair not fully defined.", "mechanism": "BRCA1 mutations predispose to TNBC and sensitize tumors to PARP inhibitors.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "causal", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "ABCC1 is a glycoprotein; glycosylation is required for proper membrane localization.", "mechanism": "ABCC1 overexpression mediates efflux of chemotherapeutics, causing multidrug resistance in TNBC.", "protein": "ABCC1 (MRP1)", "relationship_type": "causal", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "ABCG2 is a glycoprotein; N-glycosylation is essential for function.", "mechanism": "ABCG2 overexpression leads to efflux of drugs like 5-FU and olaparib, conferring resistance.", "protein": "ABCG2 (BCRP)", "relationship_type": "causal", "source_pmcid": "PMC10672974" }, { "confidence": "medium", "disease": "Chemoresistance", "glycan_involvement": "ABCC11 is a glycoprotein; glycosylation affects trafficking and activity.", "mechanism": "ABCC11 upregulation in TNBC increases drug efflux and resistance to chemotherapy.", "protein": "ABCC11 (MRP8)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Plays a role in physiological processes involving bile aci", "gene_name": "ABCC11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q96J66" }, "relationship_type": "causal", "source_pmcid": "PMC10672974" }, { "confidence": "medium", "disease": "Metastasis", "glycan_involvement": "CD44 is heavily glycosylated; glycan modifications regulate ligand binding and migration.", "mechanism": "CD44 is a marker of cancer stem cells and is associated with EMT and metastasis in TNBC.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10672974" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "MUC1 is a mucin-type glycoprotein; aberrant O-glycosylation promotes tumor progression.", "mechanism": "MUC1 is overexpressed in some TNBCs and is linked to poor prognosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672974" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL6 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Promotes inflammation, synovial hyperplasia, and bone resorption in RA; down-regulated by F. nubicola treatment.", "protein": "Interleukin-6 (IL6)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL1\u03b2 is glycosylated; glycosylation modulates activity.", "mechanism": "Drives synovial inflammation, pannus formation, and bone erosion; reduced by F. nubicola.", "protein": "Interleukin-1 beta (IL1\u03b2)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "Tnf", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16599" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "TNF\u03b1 is glycosylated; glycosylation influences receptor binding.", "mechanism": "Master regulator of pro-inflammatory cytokine cascade in RA; down-regulated by F. nubicola.", "protein": "Tumor necrosis factor alpha (TNF\u03b1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "MMP2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Degrades extracellular matrix, contributing to joint destruction; expression reduced by F. nubicola.", "protein": "Matrix metalloproteinase-2 (MMP2)", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "Mmp2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P33436" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "MMP3 is glycosylated; glycosylation modulates enzyme function.", "mechanism": "Degrades non-collagen matrix, promotes cartilage damage; down-regulated by F. nubicola.", "protein": "Matrix metalloproteinase-3 (MMP3)", "protein_enriched": { "function": "Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III colla", "gene_name": "Mmp13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P33435" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "MMP9 is glycosylated; glycosylation required for secretion and activity.", "mechanism": "Mediates matrix degradation and joint damage; reduced by F. nubicola.", "protein": "Matrix metalloproteinase-9 (MMP9)", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (By", "gene_name": "Mmp9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P50282" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "VEGF is glycosylated; glycosylation critical for receptor binding and function.", "mechanism": "Promotes angiogenesis and synovial inflammation; expression reduced by F. nubicola.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672992" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Regulates transcription of inflammatory cytokines and MMPs; activity reduced by F. nubicola.", "protein": "Nuclear factor kappa B (NF-\u03baB)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10672992" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Key mediator of inflammation and pain in RA; levels reduced by F. nubicola.", "protein": "Prostaglandin E2 (PGE2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10672992" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "ALP is glycosylated; glycosylation affects stability and activity.", "mechanism": "Elevated in RA as a marker of bone turnover; normalized by F. nubicola.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10672992" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "PD-1 is glycosylated; glycosylation affects cell surface expression and immune regulation.", "mechanism": "PD-1 deletion in mice leads to spontaneous myocarditis via anti-cTn autoantibodies.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "CTLA-4 glycosylation regulates its stability and immune checkpoint function.", "mechanism": "CTLA-4 knockout mice rapidly develop autoimmune myocarditis mediated by CD8+ T cells.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "PD-L1 glycosylation modulates its stability and immune inhibitory function.", "mechanism": "Myocardial PD-L1 overexpression is a cardioprotective response in T-cell-mediated myocarditis; anti-PD-L1 antibodies reverse this.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "protective", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Myocarditis", "glycan_involvement": "Troponin is glycosylated, affecting its serum stability and detection.", "mechanism": "Elevated serum troponin is prognostic for myocarditis severity and outcome.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "BNP is glycosylated, influencing its secretion and half-life.", "mechanism": "BNP/NT-proBNP levels indicate myocardial strain and are used in myocarditis and heart failure monitoring.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC10673034" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "HLA glycosylation is essential for antigen presentation.", "mechanism": "HLA immunostaining in biopsy aids diagnosis of immune-mediated myocarditis.", "protein": "HLA", "relationship_type": "biomarker", "source_pmcid": "PMC10673034" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "CD3 glycosylation affects T-cell receptor function.", "mechanism": "CD3 immunostaining identifies T-cell infiltrates in myocarditis biopsies.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC10673034" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Immunoglobulin glycosylation modulates effector function and anti-inflammatory activity.", "mechanism": "IV immunoglobulin is used as immunosuppressive therapy in steroid-refractory myocarditis.", "protein": "Immunoglobulin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10673034" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "PD-1 glycosylation affects immune regulation.", "mechanism": "PD-1 deletion in mice leads to dilated cardiomyopathy via autoimmune mechanisms.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Malignant melanoma", "glycan_involvement": "PD-L1 glycosylation modulates immune evasion and therapeutic efficacy.", "mechanism": "PD-L1 is targeted by ICIs for melanoma immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10673034" }, { "confidence": "high", "disease": "Sensorineural hearing loss", "glycan_involvement": "Autoantibody recognition of glycosylated epitopes on B2-glycoprotein I.", "mechanism": "B2-glycoprotein antibodies promote thromboembolic events and minor vasculitis in inner ear microvessels, leading to hearing loss.", "protein": "B2-glycoprotein I (Apolipoprotein H)", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Sensorineural hearing loss", "glycan_involvement": "Antibody binding to glycolipid/glycoprotein complexes.", "mechanism": "Anticardiolipin antibodies in SLE patients contribute to hearing loss via immune-mediated vascular injury.", "protein": "Cardiolipin", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Sensorineural hearing loss", "glycan_involvement": "Glycosylation of M3 receptor affects antigenicity.", "mechanism": "Autoantibodies against M3 receptor found in sicca syndrome may impair inner ear function.", "protein": "M3 muscarinic receptor", "protein_enriched": { "function": "The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the ac", "gene_name": "CHRM3", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P20309" }, "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Sensorineural hearing loss", "glycan_involvement": "Glycosylation modulates TNF-alpha stability and receptor binding.", "mechanism": "Systemic inflammation and TNF-alpha-mediated apoptosis contribute to hair cell damage; TNF-alpha neutralizers may prevent hearing loss.", "protein": "TNF-alpha", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10673047" }, { "confidence": "high", "disease": "Autoimmune inner ear disease", "glycan_involvement": "Fc glycosylation regulates effector function and immune complex formation.", "mechanism": "IgG autoantibodies mediate cytotoxic and immune complex injury to inner ear antigens.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Septicemia (Sepsis)", "glycan_involvement": "Glycosylation affects neutrophil lifespan and death pathways.", "mechanism": "Altered neutrophil apoptosis and glycoprotein expression contribute to immune dysregulation and organ damage.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation regulates adhesion and inflammatory signaling.", "mechanism": "Endothelial glycoproteins mediate leukocyte adhesion and microvascular thrombosis, leading to ischemic injury.", "protein": "Endothelial cell adhesion molecules", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "high", "disease": "Sensorineural hearing loss", "glycan_involvement": "Glycosylation critical for hair cell function and survival.", "mechanism": "Apoptosis of glycoprotein-rich hair cells in response to sepsis and ischemia leads to hearing loss.", "protein": "Cochlear hair cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Sensorineural hearing loss", "glycan_involvement": "Glycosylation influences antigenicity and immune response.", "mechanism": "Immune-mediated damage to spiral ganglion neurons via glycoprotein antigens results in hearing loss.", "protein": "Spiral ganglion glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10673047" }, { "confidence": "medium", "disease": "Brain injury", "glycan_involvement": "Glycosylation modulates fibronectin matrix assembly and cell adhesion.", "mechanism": "Fibroblast formation and fibronectin deposition contribute to microvascular thrombosis and tissue damage after sepsis/brain injury.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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glycosylation is central to its function.", "mechanism": "AlgD is essential for alginate biosynthesis, promoting biofilm formation and persistence.", "protein": "AlgD", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "LasB is secreted and may be glycosylated, affecting stability and activity.", "mechanism": "LasB elastase degrades host tissues, facilitating dissemination in sepsis.", "protein": "LasB", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Potential glycosylation may modulate activity.", "mechanism": "LasA elastase contributes to tissue destruction during infection.", "protein": "LasA", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Bloodstream infection", "glycan_involvement": "Type IV pilins are often glycosylated, influencing host interaction.", "mechanism": "PilA is required for type IV pili formation, mediating adhesion and invasion.", "protein": "PilA", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Bloodstream infection", "glycan_involvement": "Indirect; affects assembly of glycosylated pilins.", "mechanism": "PilB is essential for pilus assembly, impacting motility and biofilm formation.", "protein": "PilB", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect secretion and immunogenicity.", "mechanism": "Exotoxin A inhibits host protein synthesis, contributing to cytotoxicity.", "protein": "ToxA", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Biofilm-associated infection", "glycan_involvement": "Glycosylation may stabilize enzyme or modulate activity.", "mechanism": "Alkaline protease degrades host proteins, aiding immune evasion.", "protein": "AprA", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Possible glycosylation affects secretion.", "mechanism": "Hemolytic phospholipase C damages host cell membranes.", "protein": "PlcH", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "Glycosylation may affect assembly/function.", "mechanism": "TssC (T6SS) is linked to biofilm-specific antibiotic resistance.", "protein": "TssC", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "medium", "disease": "Antibiotic resistance", "glycan_involvement": "Glycosylation may influence porin stability and function.", "mechanism": "OprD porin loss or modification confers carbapenem resistance.", "protein": "OprD", "relationship_type": "causal", "source_pmcid": "PMC10673103" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Muc2 is heavily O-glycosylated; glycosylation is essential for mucus barrier function.", "mechanism": "PEG400 reduces Muc2 levels, thinning the mucus layer and compromising the intestinal barrier, leading to inflammation.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673170" }, { "confidence": "high", "disease": "Intestinal mucosal injury", "glycan_involvement": "O-glycosylation of Muc2 is critical for its protective function.", "mechanism": "Reduced Muc2 leads to loss of mucosal integrity and increased susceptibility to injury.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673170" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated, which may affect its secretion and stability.", "mechanism": "PEG400 increases IL-1\u03b2, indicating and promoting inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC10673170" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "IL-10 glycosylation may modulate its anti-inflammatory activity.", "mechanism": "PEG400 decreases IL-10, reducing anti-inflammatory protection.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC10673170" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "O-glycosylation is essential for Muc2 gel formation.", "mechanism": "Loss of Muc2 weakens the mucus barrier, increasing susceptibility to diarrhea.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673170" }, { "confidence": "medium", "disease": "Intestinal mucosal injury", "glycan_involvement": "PC is associated with glycoprotein-rich mucosal surfaces.", "mechanism": "PEG400 decreases PC, which is important for mucosal protection.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "protective", "source_pmcid": "PMC10673170" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "LPC interacts with glycoprotein receptors (e.g., TLRs).", "mechanism": "PEG400 increases LPC, which promotes inflammation via immune cell activation.", "protein": "Lysophosphatidylcholine (LPC)", "relationship_type": "causal", "source_pmcid": "PMC10673170" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Muc2 O-glycans modulate microbiota composition.", "mechanism": "Altered Muc2 and microbiota composition (e.g., increased A. muciniphila) may reduce obesity risk.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10673170" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects IL-10 stability and function.", "mechanism": "Reduced IL-10 may contribute to metabolic dysregulation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC10673170" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "O-glycosylation is essential for barrier function.", "mechanism": "Disrupted Muc2 barrier may contribute to metabolic endotoxemia.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673170" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike binding and viral entry.", "mechanism": "ACE2 acts as the main entry receptor for SARS-CoV-2 via its glycosylated extracellular domain.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycans shield epitopes and affect infectivity.", "mechanism": "Spike glycoprotein mediates viral attachment and fusion with host cells expressing ACE2.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "medium", "disease": "Post-COVID-19 syndrome (PCS)", "glycan_involvement": "Glycosylation status may affect ACE2 stability and function post-infection.", "mechanism": "Downregulation of ACE2 after infection disrupts gut homeostasis, contributing to PCS symptoms.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "medium", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "N-glycosylation influences ACE2 localization and function in the gut.", "mechanism": "Reduced ACE2 impairs amino acid absorption and antimicrobial peptide production, promoting dysbiosis and IBS.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "medium", "disease": "Post-infection IBS (PI-IBS)", "glycan_involvement": "Glycosylation may affect secretion and stability in stool.", "mechanism": "Elevated fecal calprotectin indicates intestinal inflammation in PI-IBS after COVID-19.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10673195" }, { "confidence": "medium", "disease": "Post-infection IBS (PI-IBS)", "glycan_involvement": "Spike glycosylation affects immune evasion and persistence.", "mechanism": "Persistent viral shedding and spike-mediated epithelial damage may trigger PI-IBS.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "low", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "Glycosylation required for proper trafficking and function.", "mechanism": "ACE2-dependent expression of B0AT1 is reduced, impairing tryptophan uptake and gut barrier function.", "protein": "Neutral amino acid transporter B0AT1", "protein_enriched": { "function": "The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methioni", "gene_name": "SLC7A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01650" }, "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "low", "disease": "Gastroenteritis", "glycan_involvement": "N-glycosylation modulates ACE2's protective role in the gut.", "mechanism": "ACE2 downregulation increases susceptibility to enteric infections and inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "low", "disease": "Irritable Bowel Syndrome (IBS)", "glycan_involvement": "Glycosylation may influence detection in assays.", "mechanism": "Increased calprotectin reflects ongoing low-grade inflammation in IBS patients post-COVID.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10673195" }, { "confidence": "low", "disease": "Gastroenteritis", "glycan_involvement": "Glycan shield modulates infectivity and immune response.", "mechanism": "Spike-mediated infection of GI tract leads to epithelial damage and gastroenteritis.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10673195" }, { "confidence": "high", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Fibrinogen glycosylation affects solubility and clot formation.", "mechanism": "Elevated fibrinogen increases blood viscosity, reduces cochlear blood flow, and is associated with poor SSHL prognosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates fibrinogen's interaction with other plasma proteins.", "mechanism": "High fibrinogen promotes plasma viscosity and thrombotic activation, increasing atherosclerosis risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC10673203" }, { "confidence": "medium", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Homocysteinylation can modify glycoproteins, altering vascular function.", "mechanism": "Hyperhomocysteinemia impairs endothelial function, causes microvascular dysfunction, and is associated with SSHL risk and severity.", "protein": "Homocysteine-modified proteins", "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation is essential for Factor VIII secretion and stability.", "mechanism": "Elevated Factor VIII increases thrombosis risk, contributing to SSHL via cochlear microvascular occlusion.", "protein": "Coagulation Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC10673203" }, { "confidence": "medium", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Surface glycoproteins mediate microparticle interactions.", "mechanism": "Circulating microparticles from blood cells promote thrombosis, increasing SSHL risk.", "protein": "Microparticle-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Altered glycosylation may occur in metabolic syndrome.", "mechanism": "Metabolic syndrome patients have higher fibrinogen, contributing to vascular damage and SSHL risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "medium", "disease": "Neurovascular Disease", "glycan_involvement": "Homocysteinylation can disrupt glycoprotein function.", "mechanism": "Hyperhomocysteinemia induces oxidative stress and endothelial dysfunction, increasing neurovascular disease risk.", "protein": "Homocysteine-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC10673203" }, { "confidence": "low", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Glycosylation may affect HSP70 stability and immune recognition.", "mechanism": "HSP70 is a potential prognostic biomarker for SSHL.", "protein": "Heat Shock Protein 70 (HSP70)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "low", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Glycosylation affects prestin trafficking and function.", "mechanism": "Prestin levels may indicate cochlear hair cell damage in SSHL.", "protein": "Prestin", "protein_enriched": { "function": "Antibacterial protein which inhibits the growth of E.coli and S.aureus", "gene_name": "Wfdc15b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9JHY4" }, "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "low", "disease": "Sudden Sensorineural Hearing Loss (SSHL)", "glycan_involvement": "Glycosylation determines antigenicity of endothelial cell surface proteins.", "mechanism": "Autoantibodies against endothelial glycoproteins may contribute to SSHL pathogenesis.", "protein": "Anti-endothelial cell antibody targets", "relationship_type": "biomarker", "source_pmcid": "PMC10673203" }, { "confidence": "high", "disease": "Liver abscess", "glycan_involvement": "Capsular polysaccharide is a glycan-rich structure critical for virulence.", "mechanism": "CPS enables K. pneumoniae to evade host immune response, facilitating dissemination and abscess formation.", "protein": "Klebsiella pneumoniae capsule polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC10677559" }, { "confidence": "high", "disease": "Klebsiella pneumoniae bacteremia", "glycan_involvement": "Glycosylation of CPS is essential for its anti-phagocytic properties.", "mechanism": "CPS protects bacteria from phagocytosis and complement-mediated killing, promoting bloodstream infection.", "protein": "Klebsiella pneumoniae capsule polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC10677559" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Altered host glycosylation in diabetes may increase susceptibility to CPS-expressing strains.", "mechanism": "Diabetic patients are more susceptible to CPS-mediated K. pneumoniae infections.", "protein": "Klebsiella pneumoniae capsule polysaccharide (CPS)", "relationship_type": "biomarker", "source_pmcid": "PMC10677559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation shields epitopes and modulates infectivity", "mechanism": "Spike protein mediates viral entry via ACE2 binding", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10677759" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects receptor binding and viral entry", "mechanism": "ACE2 acts as the cellular receptor for SARS-CoV-2", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10677759" }, { "confidence": "medium", "disease": "Post-COVID Conditions (PCC)", "glycan_involvement": "Glycosylation may affect antigen persistence and immune evasion", "mechanism": "Persistent viral antigens may contribute to PCC", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC10677759" }, { "confidence": "medium", "disease": "Post-COVID Conditions (PCC)", "glycan_involvement": "Glycosylation status may modulate ACE2 activity and tissue repair", "mechanism": "Altered ACE2 function post-infection may contribute to PCC", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10677759" }, { "confidence": "high", "disease": "NAFLD/NASH", "glycan_involvement": "N-glycosylation required for chaperone function and ER stress response.", "mechanism": "Highly expressed in NAFLD/NASH liver tissue and correlates with disease state.", "protein": "Hspa5 (GRP78/BiP)", "relationship_type": "biomarker", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "NASH/HCC", "glycan_involvement": "N-glycosylation affects lipid binding and plasma stability.", "mechanism": "Critically involved in hepatic triglyceride deposition; altered in tumor vs non-tumor tissue.", "protein": "Apolipoprotein A-I (Apoa1)", "relationship_type": "biomarker", "source_pmcid": "PMC10685311" }, { "confidence": "high", "disease": "NASH/HCC", "glycan_involvement": "N-glycosylation essential for receptor folding and function.", "mechanism": "Downregulated in mTOR-deficient liver/tumor tissue; impacts cholesterol uptake and serum cholesterol.", "protein": "Low-density lipoprotein receptor (Ldlr)", "relationship_type": "causal", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "NASH/HCC", "glycan_involvement": "Potential N-glycosylation may affect enzyme stability.", "mechanism": "Downregulated in NASH/HCC; low expression associated with poor HCC survival.", "protein": "Cytochrome P450 2c29 (Cyp2c29)", "protein_enriched": { "function": "Catalyzes erythromycin N-demethylation, nifedipine oxidation and testosterone 6 beta-hydroxylation", "gene_name": "Cyp3a11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q64459" }, "relationship_type": "protective", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "NASH/HCC", "glycan_involvement": "Potential N-glycosylation may affect enzyme activity.", "mechanism": "Downregulated in NASH/HCC; involved in arachidonic acid metabolism.", "protein": "Cytochrome P450 2c50 (Cyp2c50)", "protein_enriched": { "function": "Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrel", "gene_name": "16aoh-b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q64460" }, "relationship_type": "protective", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "NAFLD/NASH", "glycan_involvement": "Potential N-glycosylation may affect enzyme function.", "mechanism": "Downregulated in NASH/HCC; Cyp2j2 overexpression protects against NAFLD.", "protein": "Cytochrome P450 2j5 (Cyp2j5)", "protein_enriched": { "function": "The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from t", "gene_name": "Copa", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28681TP", "G80920RR", "G07755XJ", "G20706XG", "G49108TO" ], "uniprot_id": "Q8CIE6" }, "relationship_type": "protective", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "Obesity/NASH", "glycan_involvement": "Potential N-glycosylation may affect enzyme function.", "mechanism": "Upregulated in mTOR-knockout; Cyp2a5\u2212/\u2212 mice more sensitive to diet-induced obesity and steatosis.", "protein": "Cytochrome P450 2a5 (Cyp2a5)", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9QZR9" }, "relationship_type": "protective", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "HCC", "glycan_involvement": "Potential N-glycosylation may affect enzyme function.", "mechanism": "Strongly elevated in DEN-induced HCC and mTOR-knockout tumors; involved in hepatic toxin response.", "protein": "Cytochrome P450 2a4 (Cyp2a4)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase that selectively catalyzes the epoxidation of 14,15 double bond of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) forming 14,15-epoxyeicosatrienoic acid (14,15-EE", "gene_name": "Cyp2c29", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q64458" }, "relationship_type": "biomarker", "source_pmcid": "PMC10685311" }, { "confidence": "medium", "disease": "Cholestasis/HCC", "glycan_involvement": "Potential N-glycosylation may affect enzyme stability.", "mechanism": "Depleted in mTOR-knockout tumors; regulates primary bile acid biosynthesis.", "protein": "Cytochrome P450 7a1 (Cyp7a1)", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "Acan", "glycan_count": 6, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G05724UK", "G39188ZX", "G41247ZX", "G86182NS", "G62765YT", "G43223CG" ], "uniprot_id": "Q61282" }, "relationship_type": "causal", "source_pmcid": "PMC10685311" }, { "confidence": "high", "disease": "Cholestasis/HCC", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Decreased in mTOR-knockout tumors; impaired bile acid export linked to cholestasis and HCC progression.", "protein": "Bile salt export pump (Abcb11)", "protein_enriched": { "function": "Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih) (PubMed:10962006, Pub", "gene_name": "Hcn2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O88703" }, "relationship_type": "causal", "source_pmcid": "PMC10685311" }, { "confidence": "high", "disease": "Frailty", "glycan_involvement": "GDF15 is a glycoprotein; glycosylation may affect its stability and bioactivity.", "mechanism": "Elevated GDF15 is associated with inflammation and cell senescence, correlating with increased odds of frailty.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC10738701" }, { "confidence": "high", "disease": "Frailty", "glycan_involvement": "CNTN1 is heavily glycosylated; glycosylation is critical for its cell adhesion and signalling functions.", "mechanism": "Lower CNTN1, involved in nervous system development and signalling, is associated with higher odds of frailty.", "protein": "CNTN1", "relationship_type": "biomarker", "source_pmcid": "PMC10738701" }, { "confidence": "medium", "disease": "Prefrailty", "glycan_involvement": "Potential glycosylation may regulate HMGCS1 stability and localization.", "mechanism": "Higher HMGCS1, a regulator of cholesterol synthesis, is associated with increased odds of prefrailty.", "protein": "HMGCS1", "relationship_type": "biomarker", "source_pmcid": "PMC10738701" }, { "confidence": "medium", "disease": "Prefrailty", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Lower DUSP13A, involved in cell apoptosis, is associated with increased odds of prefrailty.", "protein": "DUSP13A", "relationship_type": "biomarker", "source_pmcid": "PMC10738701" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its stability and serum half-life.", "mechanism": "Elevated ALT levels indicate hepatocellular injury associated with NAFLD.", "protein": "alanine aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10738866" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may modulate ALT's detection and clearance.", "mechanism": "ALT elevation reflects liver inflammation and damage in NASH.", "protein": "alanine aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10738866" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST glycosylation may influence its serum levels.", "mechanism": "AST is released during liver cell injury, correlating with NAFLD severity.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC10738866" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may affect AST's function and clearance.", "mechanism": "AST elevation is a marker of hepatocellular damage in NASH.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC10738866" }, { "confidence": "high", "disease": "Renal amyloidosis (AL type)", "glycan_involvement": "Glycosylation of light chains affects aggregation and amyloidogenicity.", "mechanism": "Deposition of misfolded glycosylated light chains in glomeruli and vessels causes amyloid formation and renal dysfunction.", "protein": "Immunoglobulin light chain (AL)", "relationship_type": "causal", "source_pmcid": "PMC10775241" }, { "confidence": "high", "disease": "Renal amyloidosis (AA type)", "glycan_involvement": "Glycosylation modulates SAA clearance and deposition.", "mechanism": "Chronic inflammation increases SAA, which deposits as amyloid in kidney.", "protein": "Serum amyloid A (AA)", "relationship_type": "causal", "source_pmcid": "PMC10775241" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Abnormal glycosylation may affect renal deposition.", "mechanism": "Monoclonal Ig or light chains detected in serum/urine; associated with renal amyloidosis.", "protein": "Immunoglobulin (Ig)", "relationship_type": "biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy (TMA)", "glycan_involvement": "Glycosylation affects complement activation and regulation.", "mechanism": "Mutations or dysregulation in complement glycoproteins lead to endothelial injury and TMA.", "protein": "Complement proteins", "relationship_type": "causal", "source_pmcid": "PMC10775241" }, { "confidence": "medium", "disease": "Periodontitis in CKD", "glycan_involvement": "O-glycosylation critical for mucin function and oral protection.", "mechanism": "Reduced salivary mucins in CKD contribute to poor oral health and increased periodontitis.", "protein": "Mucin (salivary mucins)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "low", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation status changes in CKD.", "mechanism": "Altered glycosylation (carbohydrate-deficient transferrin) may reflect CKD-related metabolic changes.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation essential for stability and activity.", "mechanism": "Glycosylated erythropoietin is used to treat anemia in CKD.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10775241" }, { "confidence": "high", "disease": "IgA nephropathy", "glycan_involvement": "O-glycosylation defects in IgA1 hinge region drive disease.", "mechanism": "Aberrantly glycosylated IgA1 deposits in glomeruli, causing nephropathy.", "protein": "IgA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "medium", "disease": "IgA nephropathy", "glycan_involvement": "Glycosylation affects exosome composition and targeting.", "mechanism": "Urinary exosomal glycoproteins (including miRNA carriers) reflect glomerular injury.", "protein": "Exosomal glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "low", "disease": "Proteinuria", "glycan_involvement": "Glycosylation status may modulate renal handling.", "mechanism": "Glycation/glycosylation of albumin may affect filtration and reabsorption in CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10775241" }, { "confidence": "high", "disease": "Pheochromocytoma", "glycan_involvement": "Chromogranin A is glycosylated, which affects its stability and secretion; glycosylation may influence its detectability as a biomarker.", "mechanism": "Chromogranin A is secreted by neuroendocrine cells and elevated in pheochromocytoma due to increased tumor mass and secretory activity.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC10784937" }, { "confidence": "medium", "disease": "Catecholamine-induced cardiomyopathy", "glycan_involvement": "Glycosylation of Chromogranin A may affect its circulating levels and diagnostic utility.", "mechanism": "Elevated Chromogranin A reflects neuroendocrine activity and correlates with excessive catecholamine release, which can cause cardiomyopathy.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC10784937" }, { "confidence": "high", "disease": "ATTR cardiac amyloidosis", "glycan_involvement": "Glycosylation affects ATTR stability and aggregation.", "mechanism": "Deposition of misfolded ATTR glycoprotein in cardiac tissue leads to amyloidosis.", "protein": "Amyloid transthyretin (ATTR)", "relationship_type": "causal", "source_pmcid": "PMC10798254" }, { "confidence": "high", "disease": "AL amyloidosis", "glycan_involvement": "Glycosylation modulates aggregation propensity.", "mechanism": "Misfolded glycosylated immunoglobulin light chains deposit as amyloid in organs.", "protein": "Immunoglobulin light-chain (AL)", "relationship_type": "causal", "source_pmcid": "PMC10798254" }, { "confidence": "high", "disease": "Differentiated thyroid cancer", "glycan_involvement": "Glycosylation affects thyroglobulin secretion and immunogenicity.", "mechanism": "Serum thyroglobulin is used as a tumor marker for disease monitoring.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "medium", "disease": "Differentiated thyroid cancer", "glycan_involvement": "Glycosylation of IgG modulates immune response.", "mechanism": "Anti-thyroglobulin antibodies interfere with thyroglobulin measurement and indicate autoimmunity.", "protein": "Anti-thyroglobulin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "high", "disease": "Primary hyperparathyroidism", "glycan_involvement": "Glycosylation affects PTH stability and bioactivity.", "mechanism": "Elevated PTH is diagnostic for primary hyperparathyroidism.", "protein": "Parathyroid hormone (PTH)", "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "high", "disease": "Primary aldosteronism", "glycan_involvement": "Glycosylation regulates CXCR4 cell surface expression.", "mechanism": "CXCR4 is overexpressed in aldosterone-producing adenomas, enabling PET imaging for diagnosis.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10798254" }, { "confidence": "medium", "disease": "Takayasu arteritis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its function.", "mechanism": "CRP is used as an inflammatory marker to assess disease activity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "medium", "disease": "ATTR cardiac amyloidosis", "glycan_involvement": "Glycosylation affects NT-proBNP clearance.", "mechanism": "NT-proBNP is elevated in cardiac amyloidosis and correlates with disease severity.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "high", "disease": "ATTR cardiac amyloidosis", "glycan_involvement": "Glycosylation influences aggregation and amyloidogenicity.", "mechanism": "Wild-type or mutant transthyretin forms amyloid deposits in the heart.", "protein": "Transthyretin", "relationship_type": "causal", "source_pmcid": "PMC10798254" }, { "confidence": "low", "disease": "Takayasu arteritis", "glycan_involvement": "Indirect; glycoprotein content of plasma affects ESR.", "mechanism": "ESR is used as a non-specific marker of inflammation in vasculitis.", "protein": "Erythrocyte sedimentation rate (ESR)", "relationship_type": "biomarker", "source_pmcid": "PMC10798254" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Glycosylation of vWF is essential for its function and clearance; altered glycosylation may affect susceptibility to shear stress.", "mechanism": "Loss of functional vWF due to shear stress from mitral regurgitation may cause acquired platelet dysfunction.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10800223" }, { "confidence": "medium", "disease": "Gastric Ulcerations and Erosions (GUE)", "glycan_involvement": "Glycosylation affects vWF stability and interaction with platelets.", "mechanism": "Acquired platelet dysfunction from loss of functional vWF may increase risk of GI bleeding and ulceration in MMVD.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10800223" }, { "confidence": "high", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "NT-proBNP is glycosylated, which affects its stability and detection in assays.", "mechanism": "Elevated NT-proBNP levels are associated with CHF and can discriminate CHF from non-cardiac dyspnea.", "protein": "N-terminal pro-B-type natriuretic peptide (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC10800223" }, { "confidence": "high", "disease": "Respiratory Dyspnea", "glycan_involvement": "Glycosylation impacts NT-proBNP assay sensitivity.", "mechanism": "NT-proBNP levels help distinguish cardiac from non-cardiac causes of dyspnea.", "protein": "N-terminal pro-B-type natriuretic peptide (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC10800223" }, { "confidence": "medium", "disease": "Hyperthyroidism", "glycan_involvement": "Glycosylation may affect NT-proBNP clearance and measurement.", "mechanism": "NT-proBNP levels decrease after radioiodine therapy in hyperthyroid cats, reflecting improved cardiac function.", "protein": "N-terminal pro-B-type natriuretic peptide (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC10800223" }, { "confidence": "high", "disease": "Alcoholic Liver Injury (ALI)", "glycan_involvement": "CD36 is N-glycosylated, which affects its stability and function in lipid uptake.", "mechanism": "Promotes triglyceride accumulation and lipid-induced ER stress; DBTVS suppresses CD36 expression, reducing lipid accumulation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10804116" }, { "confidence": "high", "disease": "Alcoholic Liver Injury (ALI)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Key enzyme in long-chain polyunsaturated fatty acid synthesis; DBTVS suppresses FADS2, reducing lipid synthesis.", "protein": "FADS2", "protein_enriched": { "function": "Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precur", "gene_name": "Fads2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z122" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10804116" }, { "confidence": "medium", "disease": "Alcoholic Liver Injury (ALI)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Involved in fatty acid \u03b2-oxidation; DBTVS suppresses ACAA1, modulating lipid metabolism.", "protein": "ACAA1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10804116" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "N-glycosylation of MMP9 affects secretion and activity.", "mechanism": "Upregulated by DBTVS; MMP9 degrades collagen, potentially reducing fibrosis.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "protective", "source_pmcid": "PMC10804116" }, { "confidence": "high", "disease": "Alcoholic Fatty Liver Disease", "glycan_involvement": "N-glycosylation modulates CD36 function in lipid uptake.", "mechanism": "CD36 mediates hepatic fatty acid uptake, promoting steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10804116" }, { "confidence": "medium", "disease": "Alcoholic Hepatitis", "glycan_involvement": "N-glycosylation required for CD36 surface expression.", "mechanism": "CD36-driven lipid accumulation contributes to inflammation and progression to hepatitis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10804116" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation affects MMP9 activity.", "mechanism": "MMP9 degrades extracellular matrix, potentially limiting cirrhosis progression.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "protective", "source_pmcid": "PMC10804116" }, { "confidence": "low", "disease": "Liver Cancer", "glycan_involvement": "N-glycosylation may influence CD36-mediated signaling.", "mechanism": "Chronic lipid accumulation via CD36 may promote carcinogenesis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10804116" }, { "confidence": "low", "disease": "Alcoholic Liver Injury (ALI)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Involved in bile acid synthesis; DBTVS modulates CYP7A1 expression, affecting lipid metabolism.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10804116" }, { "confidence": "low", "disease": "Alcoholic Liver Injury (ALI)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Involved in fatty acid activation; DBTVS modulates ACSL1 expression.", "protein": "ACSL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10804116" }, { "confidence": "high", "disease": "Hashimoto's disease", "glycan_involvement": "N-glycosylation affects fetuin-A stability and function in plasma.", "mechanism": "Elevated fetuin-A may contribute to insulin resistance and adipocyte dysfunction in Hashimoto's disease.", "protein": "Fetuin-A", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10805046" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "High fetuin-A inhibits insulin signaling, promoting insulin resistance.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates fetuin-A's interaction with vascular components.", "mechanism": "Elevated fetuin-A is linked to early atherogenesis via insulin resistance and adipocyte dysfunction.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "N-glycosylation influences hepatic secretion.", "mechanism": "High fetuin-A associated with metabolic dysfunction and liver steatosis.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "high", "disease": "Hashimoto's disease", "glycan_involvement": "O-glycosylation may affect CK18 stability during cell death.", "mechanism": "Elevated CK18 reflects increased apoptosis/necrosis of thyroid epithelial cells in Hashimoto's disease.", "protein": "Cytokeratin 18 (CK18)", "relationship_type": "biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "O-glycosylation may modulate CK18 release during tumor cell death.", "mechanism": "CK18 levels are increased in thyroid cancer, indicating cell turnover.", "protein": "Cytokeratin 18 (CK18)", "relationship_type": "biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Hashimoto's disease", "glycan_involvement": "Not applicable (Nrf2 is not a glycoprotein).", "mechanism": "Elevated Nrf2 may be a response to oxidative stress in Hashimoto's disease, promoting antioxidant defense.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Not applicable.", "mechanism": "High Nrf2 expression supports cancer cell survival and proliferation.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10805046" }, { "confidence": "high", "disease": "Insulin resistance (IR)", "glycan_involvement": "N-glycosylation required for receptor interaction.", "mechanism": "Fetuin-A inhibits insulin receptor tyrosine kinase, promoting IR.", "protein": "Fetuin-A", "relationship_type": "causal/biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "O-glycosylation may affect CK18 fragment release.", "mechanism": "CK18 fragments are released during hepatocyte apoptosis, serving as a marker for liver injury.", "protein": "Cytokeratin 18 (CK18)", "relationship_type": "biomarker", "source_pmcid": "PMC10805046" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation affects ALT stability and secretion.", "mechanism": "Elevated ALT is used as a surrogate marker for NAFLD diagnosis and severity.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation modulates AST activity and serum levels.", "mechanism": "High AST (>70 U/L) is independently associated with advanced fibrosis in pediatric NAFLD.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "N-glycosylation required for GGT enzymatic activity.", "mechanism": "Elevated GGT correlates with advanced fibrosis and NASH severity.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "N-glycosylation influences ALT serum half-life.", "mechanism": "ALT \u226580 U/L is predictive of underlying NASH in pediatric patients.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "IgG N-glycosylation modulates immune response and inflammation.", "mechanism": "Detection of autoantibodies prompts liver biopsy to exclude autoimmune hepatitis in NAFLD/NASH.", "protein": "Autoantibodies (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation impacts ALT detection in serum.", "mechanism": "Persistent elevation of ALT is associated with progression to cirrhosis in pediatric NAFLD.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation necessary for GGT function.", "mechanism": "Elevated GGT is associated with advanced fibrosis in NAFLD.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation required for BSEP trafficking and function.", "mechanism": "Ursodeoxycholic acid used as adjunctive therapy; BSEP glycosylation affects drug response.", "protein": "Ursodeoxycholic acid transporter (BSEP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10805478" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "IgG glycosylation modulates pathogenicity.", "mechanism": "Presence of autoantibodies may indicate autoimmune overlap in cirrhosis.", "protein": "Autoantibodies (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "N-glycosylation affects ALT serum levels.", "mechanism": "ALT elevation is a marker of liver injury in ACLF secondary to NASH cirrhosis.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10805478" }, { "confidence": "medium", "disease": "Gastrointestinal nematode (GIN) infection", "glycan_involvement": "Acetylcholinesterase is a glycoprotein; glycosylation may affect its stability and localization in nematodes.", "mechanism": "Inhibition of nematode acetylcholinesterase by plant-derived compounds leads to paralysis and death of GINs.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10805549" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Measured as part of autoimmune workup; negative result helps exclude autoimmune hepatitis.", "protein": "beta-2-glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "hepatitis", "glycan_involvement": "Glycosylation required for stability and secretion.", "mechanism": "Measured to exclude Wilson's disease as a cause of hepatitis.", "protein": "ceruloplasmin", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "hepatitis", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "Measured to exclude alpha-1 antitrypsin deficiency-related hepatitis.", "protein": "alpha-1 antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Fc glycosylation modulates immune activity.", "mechanism": "Elevated IgG can indicate autoimmune hepatitis; measured in workup.", "protein": "immunoglobulin G (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation affects antibody function.", "mechanism": "Measured as part of autoimmune workup; negative result helps exclude autoimmune hepatitis.", "protein": "immunoglobulin M (IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation required for complement activation.", "mechanism": "Low C3 can indicate autoimmune activity; measured in workup.", "protein": "complement C3", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation required for complement activation.", "mechanism": "Low C4 can indicate autoimmune activity; measured in workup.", "protein": "complement C4", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation affects antibody function.", "mechanism": "Measured to exclude autoimmune hepatitis; negative result helps exclude diagnosis.", "protein": "anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation affects antibody function.", "mechanism": "Measured to exclude autoimmune hepatitis; negative result helps exclude diagnosis.", "protein": "antismooth muscle antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "medium", "disease": "autoimmune hepatitis", "glycan_involvement": "Glycosylation affects antibody function.", "mechanism": "Measured to exclude autoimmune hepatitis; negative result helps exclude diagnosis.", "protein": "F-actin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10805563" }, { "confidence": "high", "disease": "Vascular endothelial injury", "glycan_involvement": "TRPM4 is a glycoprotein; glycosylation may affect membrane localization and function, but not directly discussed.", "mechanism": "Upregulation of TRPM4 by palmitic acid leads to calcium overload, mitochondrial dysfunction, ROS accumulation, and apoptosis in endothelial cells.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "TRPM4 glycosylation may modulate channel activity and cell surface expression.", "mechanism": "TRPM4-mediated endothelial injury contributes to atherosclerosis development; knockdown of TRPM4 protects endothelium.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ICAM-1 is heavily glycosylated; glycosylation is essential for its adhesive function.", "mechanism": "PA-induced endothelial injury increases ICAM-1 expression, promoting monocyte adhesion and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "VCAM-1 glycosylation is critical for ligand binding and cell-cell interactions.", "mechanism": "VCAM-1 upregulation facilitates leukocyte migration and plaque formation in response to endothelial injury.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "IL-1\u03b2 is upregulated in PA-induced endothelial injury, driving inflammation and plaque progression.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10806017" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation may regulate TRPM4 trafficking and function.", "mechanism": "TRPM4 mediates endothelial dysfunction in hyperlipidemia via calcium signaling and apoptosis.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10806017" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Potential role for glycosylation in TRPM4 function, not directly addressed.", "mechanism": "Obesity-associated endothelial injury involves TRPM4 upregulation and dysfunction.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10806017" }, { "confidence": "low", "disease": "Nonalcoholic fatty liver disease", "glycan_involvement": "Possible, but not directly discussed.", "mechanism": "Endothelial dysfunction in NAFLD may involve TRPM4-mediated injury.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10806017" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "TRPM4 glycosylation may affect disease-relevant channel activity.", "mechanism": "TRPM4 and its regulation by miR-133a-3p are implicated in CAD pathogenesis.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Vascular endothelial injury", "glycan_involvement": "Glycosylation is required for ICAM-1 function.", "mechanism": "ICAM-1 upregulation marks endothelial activation and injury.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10806017" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects effector function and complement activation.", "mechanism": "Oligoclonal IgG bands in CSF are diagnostic and may mediate complement-dependent demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10806081" }, { "confidence": "high", "disease": "Neuromyelitis Optica (NMO)", "glycan_involvement": "AQP4 is glycosylated; glycosylation may affect antibody recognition and pathogenicity.", "mechanism": "AQP4-IgG autoantibodies bind AQP4 on astrocytes, causing complement-mediated cytotoxicity and BBB disruption.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10806081" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding and depletion efficacy.", "mechanism": "CD20+ B cell depletion (e.g., rituximab) reduces proinflammatory B cells and disease activity.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Neuromyelitis Optica (NMO)", "glycan_involvement": "CD138 is highly glycosylated; glycosylation modulates cell adhesion and migration.", "mechanism": "CD138+ plasmablasts produce pathogenic AQP4-IgG; elevated in blood and CSF during relapse.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC10806081" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "HLA-DR is glycosylated; glycosylation influences peptide loading and T cell activation.", "mechanism": "B cells present antigen via HLA-DR (MHC II) to T cells, driving autoimmune responses.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "causal", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD40 is glycosylated; glycosylation may modulate receptor-ligand interactions.", "mechanism": "CD40-activated B cells enhance antigen presentation and T cell activation; blockade reduces disease.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD80 is glycosylated; glycosylation affects surface expression and function.", "mechanism": "Upregulated on B cells in MS, enhances T cell costimulation and proinflammatory responses.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "causal", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "CD86 is glycosylated; glycosylation impacts ligand binding.", "mechanism": "Increased on B cells in MS, promotes T cell activation and inflammation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "causal", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Heavily O-glycosylated; sialylation and fucosylation are critical for selectin binding.", "mechanism": "Mediates B cell rolling and transmigration into CNS via interaction with P-selectin.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC10806081" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "ALCAM is glycosylated; glycosylation may affect adhesion properties.", "mechanism": "ALCAM on B cells facilitates CNS recruitment; deficiency reduces B cell infiltration.", "protein": "ALCAM", "relationship_type": "causal", "source_pmcid": "PMC10806081" }, { "confidence": "high", "disease": "Male infertility", "glycan_involvement": "Glycosylation is crucial for TEX101's cell surface localization and function in sperm maturation.", "mechanism": "TEX101 is essential for spermatogenesis and sperm-egg interaction; CBZ binding inhibits its function, leading to impaired fertility.", "protein": "TEX101", "protein_enriched": { "function": "Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct (By similarity). May play a role in signal transduction and promote protei", "gene_name": "Tex101", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q924B5" }, "relationship_type": "biomarker", "source_pmcid": "PMC10806130" }, { "confidence": "high", "disease": "Testicular toxicity", "glycan_involvement": "Glycosylation affects GPX5 secretion and stability in the epididymis.", "mechanism": "GPX5 protects sperm DNA from oxidative damage; CBZ binding reduces GPX5 activity, increasing oxidative stress and testicular damage.", "protein": "GPX5", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-l", "gene_name": "Gpx5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30710" }, "relationship_type": "protective", "source_pmcid": "PMC10806130" }, { "confidence": "medium", "disease": "Male infertility", "glycan_involvement": "Glycosylation modulates EPPIN's interaction with other seminal proteins.", "mechanism": "EPPIN regulates sperm motility and antimicrobial protection; CBZ binding impairs EPPIN function, reducing sperm motility.", "protein": "EPPIN", "protein_enriched": { "function": "Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for sper", "gene_name": "Eppin", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "D4A2Z2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10806130" }, { "confidence": "high", "disease": "Testicular toxicity", "glycan_involvement": "Glycosylation required for TEX101's functional conformation.", "mechanism": "CBZ blocks TEX101 active sites, disrupting normal protein expression and spermatogenesis.", "protein": "TEX101", "protein_enriched": { "function": "Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct (By similarity). May play a role in signal transduction and promote protei", "gene_name": "Tex101", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q924B5" }, "relationship_type": "causal", "source_pmcid": "PMC10806130" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation influences GPX5's antioxidant activity.", "mechanism": "GPX5 activity is reduced by CBZ, increasing ROS and lipid peroxidation; restoration by moringa/flaxseed oil.", "protein": "GPX5", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-l", "gene_name": "Gpx5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30710" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10806130" }, { "confidence": "medium", "disease": "Testicular toxicity", "glycan_involvement": "Glycosylation affects EPPIN's stability and function.", "mechanism": "CBZ binding to EPPIN blocks its active sites, impairing sperm motility and testicular health.", "protein": "EPPIN", "protein_enriched": { "function": "Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for sper", "gene_name": "Eppin", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "D4A2Z2" }, "relationship_type": "causal", "source_pmcid": "PMC10806130" }, { "confidence": "medium", "disease": "Endocrine disruption", "glycan_involvement": "Glycosylation is necessary for TEX101's interaction with hormone-regulated pathways.", "mechanism": "CBZ-induced inhibition of TEX101 disrupts hormonal regulation of spermatogenesis.", "protein": "TEX101", "protein_enriched": { "function": "Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct (By similarity). May play a role in signal transduction and promote protei", "gene_name": "Tex101", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q924B5" }, "relationship_type": "causal", "source_pmcid": "PMC10806130" }, { "confidence": "high", "disease": "Male infertility", "glycan_involvement": "Glycosylation supports GPX5's protective role in sperm maturation.", "mechanism": "GPX5 maintains sperm DNA integrity; CBZ reduces GPX5, increasing infertility risk.", "protein": "GPX5", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-l", "gene_name": "Gpx5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30710" }, "relationship_type": "protective", "source_pmcid": "PMC10806130" }, { "confidence": "medium", "disease": "Testicular toxicity", "glycan_involvement": "Glycosylation status may influence therapeutic response.", "mechanism": "Restoration of TEX101 function by moringa/flaxseed oil alleviates CBZ-induced testicular toxicity.", "protein": "TEX101", "protein_enriched": { "function": "Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct (By similarity). May play a role in signal transduction and promote protei", "gene_name": "Tex101", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q924B5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10806130" }, { "confidence": "medium", "disease": "Endocrine disruption", "glycan_involvement": "Glycosylation required for GPX5's endocrine regulatory functions.", "mechanism": "CBZ impairs GPX5, leading to hormonal imbalance and testicular dysfunction.", "protein": "GPX5", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-l", "gene_name": "Gpx5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30710" }, "relationship_type": "causal", "source_pmcid": "PMC10806130" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Tsp43 is a glycoprotein; glycosylation may be important for its immunomodulatory function.", "mechanism": "Tsp43 induces IDO expression in dendritic cells, leading to reduced CD4+ T cell proliferation and increased apoptosis, thereby alleviating RA symptoms.", "protein": "T. spiralis recombinant protein 43 (Tsp43)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10807947" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "IDO is a glycoprotein; glycosylation may affect its stability and function.", "mechanism": "IDO expression suppresses CD4+ T cell proliferation and promotes apoptosis, restoring immune balance and reducing RA pathology.", "protein": "Indoleamine 2,3-dioxygenase (IDO)", "protein_enriched": { "function": "Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contrib", "gene_name": "IDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14902" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10807947" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation of Tsp43 may be required for its immunomodulatory activity.", "mechanism": "Tsp43 reduces pro-inflammatory cytokines (IL-1\u03b2, TNF-\u03b1) and joint damage in RA model mice.", "protein": "T. spiralis recombinant protein 43 (Tsp43)", "relationship_type": "protective", "source_pmcid": "PMC10807947" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycan structures on Tsp43 may mediate interaction with dendritic cells.", "mechanism": "Tsp43 treatment leads to increased IDO expression, which in turn suppresses pathogenic CD4+ T cell responses in RA.", "protein": "T. spiralis recombinant protein 43 (Tsp43)", "relationship_type": "causal (protective)", "source_pmcid": "PMC10807947" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation may influence IDO's enzymatic activity.", "mechanism": "High IDO activity depletes tryptophan, inhibiting T cell function and proliferation, thus reducing RA severity.", "protein": "Indoleamine 2,3-dioxygenase (IDO)", "protein_enriched": { "function": "Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contrib", "gene_name": "IDO1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14902" }, "relationship_type": "protective", "source_pmcid": "PMC10807947" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation may be necessary for Tsp43's biological activity.", "mechanism": "Tsp43-induced IDO expression can be blocked by 1-methyl-tryptophan (1-MT), reversing its therapeutic effects.", "protein": "T. spiralis recombinant protein 43 (Tsp43)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10807947" }, { "confidence": "high", "disease": "Memory impairment", "glycan_involvement": "Cbln4 is a secreted glycoprotein; glycosylation may affect synaptic targeting.", "mechanism": "Cbln4 deletion in PFC reduces GABAergic and glutamatergic synapses, impairing remote memory recall.", "protein": "Cerebellin-4 (Cbln4)", "relationship_type": "causal", "source_pmcid": "PMC10829571" }, { "confidence": "high", "disease": "Neuropsychiatric disorders", "glycan_involvement": "Heavily glycosylated; glycan modifications regulate synaptic interactions.", "mechanism": "Neurexin mutations disrupt synapse specificity, linked to behavioral abnormalities.", "protein": "Neurexins", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Zonulin is a glycoprotein; glycosylation may regulate secretion/function.", "mechanism": "Elevated plasma zonulin indicates increased gut permeability, associated with SCZ pathophysiology.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "LBP is glycosylated; glycosylation affects stability and immune recognition.", "mechanism": "Elevated LBP reflects systemic inflammation and altered gut-brain axis in SCZ.", "protein": "Lipopolysaccharide-binding protein (LBP)", "protein_enriched": { "function": "Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:2412035", "gene_name": "LBP", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G84452RH", "G94470IW" ], "uniprot_id": "P18428" }, "relationship_type": "biomarker", "source_pmcid": "PMC10829571" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation modulates processing and toxicity.", "mechanism": "Caspase-cleaved APP (APP-C31) drives neurotoxicity and AD progression.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC10829571" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Derived from glycosylated APP; glycan status may affect fragment generation.", "mechanism": "APP-C31 self-propagates neurotoxicity, enhances caspase activity, and triggers neuroinflammation.", "protein": "APP-C31 fragment", "relationship_type": "causal", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TSPO is glycosylated; glycosylation may affect mitochondrial localization/function.", "mechanism": "TSPO regulates microglial metabolism and phagocytosis; loss leads to AD-like microglial dysfunction.", "protein": "Translocator protein (TSPO)", "protein_enriched": { "function": "Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipi", "gene_name": "TSPO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30536" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "HK-II is glycosylated; glycosylation may regulate enzyme activity.", "mechanism": "HK-II mitochondrial recruitment in TSPO-deficient microglia induces glycolysis and phagocytic dysfunction.", "protein": "Hexokinase-II (HK-II)", "relationship_type": "causal", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "PI3K is a glycoprotein; glycosylation may affect signaling.", "mechanism": "Amyloid \u03b2 elevates microglial miR-21-5p, downregulating PI3K-BDNF pathway, impairing LTP.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10829571" }, { "confidence": "medium", "disease": "Age-related dementia", "glycan_involvement": "BDNF is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Microglial PI3K-BDNF signaling supports synaptic plasticity; downregulation leads to cognitive impairment.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC10829571" }, { "confidence": "high", "disease": "Cerebral small vessel disease (CSVD)", "glycan_involvement": "ANGPTL4 is a secreted glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Serum ANGPTL4 levels are elevated in CSVD and correlate with disease severity.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "high", "disease": "Cognitive impairment (CI)", "glycan_involvement": "Glycosylation enables ANGPTL4's function as a circulating biomarker.", "mechanism": "Higher serum ANGPTL4 levels are associated with worse cognitive scores in CSVD patients.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "high", "disease": "White matter hyperintensity (WMH)", "glycan_involvement": "Glycosylation is essential for ANGPTL4's secretion and activity.", "mechanism": "ANGPTL4 levels increase with WMH severity (mild to moderate), suggesting involvement in white matter damage.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "high", "disease": "Cerebral small vessel disease-related cognitive impairment (CSVD-CI)", "glycan_involvement": "Glycosylation required for ANGPTL4's function as a circulating factor.", "mechanism": "ANGPTL4 is an independent risk factor for CSVD-CI after adjusting for confounders.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "independent influencing factor", "source_pmcid": "PMC10839130" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation supports ANGPTL4's stability in circulation.", "mechanism": "ANGPTL4 gene and protein expression are upregulated in AD patients.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation is necessary for ANGPTL4's secretion.", "mechanism": "Plasma ANGPTL4 levels are elevated in vascular dementia.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "medium", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Glycosylation affects ANGPTL4's function in lipid regulation.", "mechanism": "ANGPTL4 is expressed in CHD and involved in lipid metabolism.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation required for ANGPTL4's function.", "mechanism": "ANGPTL4 is expressed in hypertension and may modulate vascular function.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation supports ANGPTL4's angiogenic activity.", "mechanism": "ANGPTL4 is upregulated in ischemic stroke and may promote neovascularization.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "biomarker", "source_pmcid": "PMC10839130" }, { "confidence": "low", "disease": "White matter hyperintensity (WMH)", "glycan_involvement": "Glycosylation is necessary for ANGPTL4's biological activity.", "mechanism": "ANGPTL4 may promote or inhibit angiogenesis in white matter, influencing WMH progression.", "protein": "Angiopoietin-like protein 4 (ANGPTL4)", "relationship_type": "causal (putative, context-dependent)", "source_pmcid": "PMC10839130" }, { "confidence": "high", "disease": "Oesophageal squamous cell carcinoma", "glycan_involvement": "Nivolumab is an N-glycosylated IgG4 antibody; glycosylation affects stability and effector function", "mechanism": "Blocks PD-1/PD-L1 interaction, enhancing anti-tumor immune response", "protein": "Nivolumab (anti-PD-1 IgG4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10849177" }, { "confidence": "medium", "disease": "Oesophageal squamous cell carcinoma", "glycan_involvement": "CEA is heavily N-glycosylated; altered glycosylation may affect detection and function", "mechanism": "CEA is used as a tumor marker for monitoring disease progression or recurrence", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC10849177" }, { "confidence": "medium", "disease": "Oesophageal squamous cell carcinoma", "glycan_involvement": "SCC-Ag is a glycoprotein; glycosylation may influence antigenicity", "mechanism": "SCC-Ag is used as a tumor marker for diagnosis and monitoring", "protein": "Squamous cell carcinoma-associated antigen (SCC-Ag)", "relationship_type": "biomarker", "source_pmcid": "PMC10849177" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "ANA are glycoproteins with glycosylation affecting antigenicity.", "mechanism": "ANA is typically used as a serological marker for AIH diagnosis.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "ASMA are glycoproteins; glycosylation may influence immune recognition.", "mechanism": "ASMA can serve as a diagnostic marker for AIH, especially when ANA is negative.", "protein": "Anti-Smooth Muscle Antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "medium", "disease": "Acute Hepatitis", "glycan_involvement": "ALT is glycosylated, which may affect its stability and serum levels.", "mechanism": "Elevated ALT indicates hepatocellular injury in acute hepatitis.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "medium", "disease": "Acute Hepatitis", "glycan_involvement": "AST glycosylation may modulate its serum half-life.", "mechanism": "Elevated AST is a marker of liver cell damage.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "Bilirubin is transported bound to glycoproteins (albumin); glycosylation affects transport.", "mechanism": "Elevated bilirubin is a direct indicator of jaundice due to liver dysfunction.", "protein": "Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "GGT is glycosylated, influencing its enzymatic activity.", "mechanism": "Normal GGT helps differentiate AIH from cholestatic liver diseases.", "protein": "Gamma-Glutamyl Transferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "ALP glycosylation affects its serum activity and stability.", "mechanism": "Normal ALP supports diagnosis of AIH over cholestatic conditions.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC10871918" }, { "confidence": "high", "disease": "Microvillus Inclusion Disease (MVID)", "glycan_involvement": "MYO5B affects trafficking of glycoproteins, but not directly glycosylation.", "mechanism": "Biallelic MYO5B mutations disrupt intracellular trafficking of brush border proteins in the intestine.", "protein": "MYO5B (Myosin Vb)", "protein_enriched": { "function": "Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Can hydrolyze ATP in the presence of actin, which is essential for its function a", "gene_name": "MYO5A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4I1" }, "relationship_type": "causal", "source_pmcid": "PMC10871919" }, { "confidence": "high", "disease": "Cholestatic Liver Disease", "glycan_involvement": "Indirect; MYO5B affects localization of glycoproteins such as BSEP and MDR3.", "mechanism": "MYO5B mutations disrupt trafficking of canalicular bile acid and bilirubin transporting proteins in hepatocytes.", "protein": "MYO5B (Myosin Vb)", "protein_enriched": { "function": "Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Can hydrolyze ATP in the presence of actin, which is essential for its function a", "gene_name": "MYO5A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4I1" }, "relationship_type": "causal", "source_pmcid": "PMC10871919" }, { "confidence": "high", "disease": "PFIC-like phenotype", "glycan_involvement": "Indirect; trafficking of canalicular glycoproteins is affected.", "mechanism": "MYO5B mutations lead to impaired bile secretion and cholestasis with normal GGT, mimicking PFIC.", "protein": "MYO5B (Myosin Vb)", "protein_enriched": { "function": "Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Can hydrolyze ATP in the presence of actin, which is essential for its function a", "gene_name": "MYO5A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4I1" }, "relationship_type": "causal", "source_pmcid": "PMC10871919" }, { "confidence": "medium", "disease": "Cholestatic Liver Disease", "glycan_involvement": "BSEP is a glycoprotein; proper glycosylation is required for function and trafficking.", "mechanism": "Impaired canalicular localization of BSEP due to MYO5B mutations leads to defective bile acid export.", "protein": "BSEP (Bile Salt Export Pump)", "relationship_type": "causal", "source_pmcid": "PMC10871919" }, { "confidence": "medium", "disease": "Cholestatic Liver Disease", "glycan_involvement": "MDR3 is a glycoprotein; glycosylation affects stability and trafficking.", "mechanism": "Impaired canalicular localization of MDR3 due to MYO5B mutations leads to defective phospholipid transport.", "protein": "MDR3 (Multidrug Resistance Protein 3)", "relationship_type": "causal", "source_pmcid": "PMC10871919" }, { "confidence": "medium", "disease": "PFIC-like phenotype", "glycan_involvement": "Glycosylation status may affect BSEP detection and function.", "mechanism": "Loss of canalicular BSEP staining in liver biopsy is indicative of impaired bile acid transport.", "protein": "BSEP (Bile Salt Export Pump)", "relationship_type": "biomarker", "source_pmcid": "PMC10871919" }, { "confidence": "medium", "disease": "PFIC-like phenotype", "glycan_involvement": "Glycosylation status may affect MDR3 detection and function.", "mechanism": "Loss of canalicular MDR3 staining in liver biopsy is indicative of impaired phospholipid transport.", "protein": "MDR3 (Multidrug Resistance Protein 3)", "relationship_type": "biomarker", "source_pmcid": "PMC10871919" }, { "confidence": "high", "disease": "Rett syndrome (RTT)", "glycan_involvement": "No direct glycosylation involvement described for MECP2 in this article.", "mechanism": "Loss-of-function mutations in MECP2 cause RTT by disrupting neuronal development and function.", "protein": "MECP2", "protein_enriched": { "function": "Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression ", "gene_name": "MECP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51608" }, "relationship_type": "causal", "source_pmcid": "PMC10871965" }, { "confidence": "medium", "disease": "Steatotic liver disease (SLD)", "glycan_involvement": "No direct glycosylation involvement described for MECP2 in SLD in this article.", "mechanism": "MECP2 mutations perturb peripheral lipid metabolism, leading to hepatic steatosis.", "protein": "MECP2", "protein_enriched": { "function": "Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression ", "gene_name": "MECP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51608" }, "relationship_type": "causal", "source_pmcid": "PMC10871965" }, { "confidence": "medium", "disease": "Dyslipidemia (DLD)", "glycan_involvement": "No direct glycosylation involvement described for MECP2 in DLD in this article.", "mechanism": "MECP2 mutations disrupt lipid metabolism, resulting in elevated triglycerides and LDL.", "protein": "MECP2", "protein_enriched": { "function": "Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression ", "gene_name": "MECP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51608" }, "relationship_type": "causal", "source_pmcid": "PMC10871965" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Alters glycosylation of MUC2, increasing sialylated/fucosylated glycans.", "mechanism": "Missense mutation in FCGBP disrupts mucus barrier integrity, increasing susceptibility to inflammation.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10872041" }, { "confidence": "medium", "disease": "Colon Cancer", "glycan_involvement": "Mutation increases sialylation/fucosylation of MUC2.", "mechanism": "Altered glycosylation profile (sialylated/fucosylated glycans) is a hallmark of colon cancer.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10872041" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Increase in sialylated/fucosylated glycans impairs barrier.", "mechanism": "Loss of MUC2 barrier function due to altered glycosylation increases disease risk.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC10872041" }, { "confidence": "medium", "disease": "Colon Cancer", "glycan_involvement": "Sialylated/fucosylated glycan signature.", "mechanism": "Altered glycosylation of MUC2 is associated with colon cancer.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872041" }, { "confidence": "high", "disease": "Salmonella enterica infection", "glycan_involvement": "Sialylated/fucosylated glycans facilitate pathogen binding.", "mechanism": "Altered glycosylation increases penetrability and susceptibility to bacterial invasion.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC10872041" }, { "confidence": "medium", "disease": "Salmonella enterica infection", "glycan_involvement": "Indirect via altered MUC2 glycosylation.", "mechanism": "Mutation leads to increased metabolic stress and ROS, enhancing cell death upon infection.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10872041" }, { "confidence": "low", "disease": "Colon Cancer", "glycan_involvement": "Targets abnormal sialylation/fucosylation.", "mechanism": "Restoring FCGBP function may normalize glycosylation and barrier integrity.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10872041" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Sialylated/fucosylated glycan increase.", "mechanism": "Altered glycan profile of MUC2 can indicate disease state.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872041" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Altered glycosylation signature.", "mechanism": "Mutation status and glycan profile may serve as disease marker.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10872041" }, { "confidence": "high", "disease": "Salmonella enterica infection", "glycan_involvement": "Proper glycosylation maintains barrier.", "mechanism": "Normal glycosylation of MUC2 prevents pathogen penetration.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC10872041" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Low ceruloplasmin is a diagnostic marker for Wilson disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Glycosylation affects folding and secretion.", "mechanism": "Deficiency can predispose to liver disease.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "Severe acute hepatitis", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated ferritin reflects acute liver injury/inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Fc glycosylation modulates immune activity.", "mechanism": "Elevated IgG is typical in autoimmune hepatitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Autoantibodies are IgG glycoproteins; glycosylation affects effector function.", "mechanism": "Presence may indicate autoimmune process.", "protein": "Anti-dense fine speckled autoantibodies (DFS70)", "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "high", "disease": "Severe acute hepatitis", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Normal ceruloplasmin helps exclude Wilson disease in acute hepatitis.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "high", "disease": "Severe acute hepatitis", "glycan_involvement": "Glycosylation affects folding and secretion.", "mechanism": "Normal levels help exclude alpha-1 antitrypsin deficiency as cause.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "COVID-19 infection", "glycan_involvement": "Glycosylation modulates antibody effector functions.", "mechanism": "IgG response is part of COVID-19 immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "Severe acute hepatitis", "glycan_involvement": "Albumin is glycosylated; glycosylation affects half-life.", "mechanism": "Albumin levels reflect liver synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "medium", "disease": "COVID-19 infection", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated ferritin is seen in COVID-19-related inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10872176" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "VP40 is a glycoprotein that interacts with host plasma membrane lipids, but direct glycosylation is not the focus; rather, lipid binding modulates its function.", "mechanism": "VP40 is essential for Ebola virus assembly and budding from the host cell plasma membrane, enabling viral propagation.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycan modification; function depends on electrostatic interactions with anionic phospholipids.", "mechanism": "Mutations in VP40 lysine-rich regions disrupt PI(4,5)P2 binding, oligomerization, and virus-like particle (VLP) release, suggesting these sites as antiviral targets.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; function mediated by lipid binding.", "mechanism": "Region 1 lysine residues (Lys221, Lys224, Lys225) are critical for formation of large VP40 oligomers, necessary for viral matrix assembly.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; function mediated by lipid binding.", "mechanism": "Region 2 lysine residues (Lys270, Lys274, Lys275, Lys279) stabilize VP40 oligomers via PI(4,5)P2 binding, promoting efficient VLP release.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; interaction is with host membrane lipids.", "mechanism": "PS (phosphatidylserine) binding by VP40 is required for initial membrane association and conformational change, a prerequisite for viral assembly.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; effect is via lipid-protein interaction.", "mechanism": "Depletion of PI(4,5)P2 in host cells inhibits VP40 oligomerization and VLP formation, indicating a potential antiviral strategy.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; effect is via lipid binding.", "mechanism": "Mutation of Lys225 (region 1) reduces VLP formation by 85%, indicating its essential role in viral budding.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; effect is via lipid binding.", "mechanism": "Mutation of Lys274 or Lys275 (region 2) abolishes VLP formation, showing their necessity for late-stage budding.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; effect is via conformational stabilization.", "mechanism": "Residues 57\u201373 in VP40 N-terminal domain are stabilized by PI(4,5)P2 binding, supporting dimer and oligomer stability required for viral assembly.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "causal", "source_pmcid": "PMC10909612" }, { "confidence": "medium", "disease": "Ebola virus disease (EVD)", "glycan_involvement": "No direct glycosylation; effect is via lipid-protein interface.", "mechanism": "Targeting VP40-lipid interactions (especially PI(4,5)P2 binding sites) could disrupt viral assembly and budding.", "protein": "Ebola virus matrix protein VP40", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10909612" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects BNP stability and clearance.", "mechanism": "BNP is released in response to ventricular stretch and volume overload, reflecting heart failure severity.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC10910697" }, { "confidence": "high", "disease": "Infective endocarditis", "glycan_involvement": "CRP is N-glycosylated, which modulates its immune recognition.", "mechanism": "CRP is elevated during acute infection and inflammation, including endocarditis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910697" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Albumin glycosylation can affect its half-life and function.", "mechanism": "Serum albumin levels reflect nutritional and inflammatory status in heart failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910697" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "SLC3A2 is a glycoprotein; glycosylation may affect its membrane localization and transporter function.", "mechanism": "Downregulation of SLC3A2 in melanocytes promotes ferroptosis via impaired cystine/glutamate transport, leading to oxidative damage and cell death.", "protein": "SLC3A2", "relationship_type": "causal", "source_pmcid": "PMC10910712" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "HLA-A is N-glycosylated, which is important for its stability and immune recognition.", "mechanism": "Upregulated HLA-A in melanocytes is associated with increased immune inflammation and antigen presentation, contributing to autoimmune attack.", "protein": "HLA-A", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "S100A4 is a glycoprotein; glycosylation may modulate its extracellular signaling.", "mechanism": "Upregulated S100A4 in melanocytes is linked to cell cycle regulation and immune inflammation.", "protein": "S100A4", "protein_enriched": { "function": "Calcium-binding protein that plays a role in various cellular processes including motility, angiogenesis, cell differentiation, apoptosis, and autophagy (PubMed:16707441, PubMed:23752197, PubMed:30713", "gene_name": "S100A4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P26447" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "BST2 is GPI-anchored and glycosylated, affecting its cell surface expression and immune signaling.", "mechanism": "Upregulated BST2 in melanocytes is enriched in immune function pathways, possibly contributing to immune dysregulation.", "protein": "BST2", "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "LGALS1 binds \u03b2-galactoside glycans, modulating cell-cell interactions and apoptosis.", "mechanism": "Upregulated LGALS1 (galectin-1) in melanocytes is involved in apoptosis pathway enrichment.", "protein": "LGALS1", "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulated CDKN2A regulates melanocyte cell cycle, potentially contributing to reduced proliferation.", "protein": "CDKN2A", "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "low", "disease": "Vitiligo", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulated ribosomal protein RPL12 in melanocytes may reflect altered protein synthesis in disease.", "protein": "RPL12", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:25901680). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:25901680). Binds directly to", "gene_name": "RPL12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30050" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "low", "disease": "Vitiligo", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulated ribosomal protein RPL29 in melanocytes may reflect altered protein synthesis in disease.", "protein": "RPL29", "protein_enriched": { "function": "Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Required for proper rRNA processing and maturation of", "gene_name": "rps27", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P47904" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "low", "disease": "Vitiligo", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulated ribosomal protein RPL31 in melanocytes may reflect altered protein synthesis in disease.", "protein": "RPL31", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, P", "gene_name": "RPL31", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62899" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910712" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "SLC3A2 glycosylation may affect transporter function in chondrocytes.", "mechanism": "Downregulation of SLC3A2 promotes chondrocyte ferroptosis in osteoarthritis.", "protein": "SLC3A2", "relationship_type": "causal", "source_pmcid": "PMC10910712" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Asprosin is a glycoprotein hormone; glycosylation is required for its secretion and stability.", "mechanism": "Elevated serum asprosin is independently associated with MAFLD in T2DM; correlates with insulin resistance and metabolic dysfunction.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Glycosylation is essential for asprosin's function as a hormone.", "mechanism": "Serum asprosin is elevated in T2DM and correlates with insulin resistance (HOMA-IR) and fasting insulin.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation supports asprosin's secretion from adipose tissue.", "mechanism": "Asprosin is elevated in obesity and correlates with BMI and triglycerides.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation maintains asprosin's stability in circulation.", "mechanism": "High asprosin levels are associated with diabetic nephropathy and inversely correlated with eGFR.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "low", "disease": "PCOS", "glycan_involvement": "Glycosylation is required for asprosin's hormonal activity.", "mechanism": "Elevated asprosin observed in PCOS, which is often associated with obesity and T2DM.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "low", "disease": "CVD", "glycan_involvement": "Glycosylation is necessary for asprosin's function.", "mechanism": "Asprosin is involved in the development of cardiovascular diseases, possibly via metabolic and inflammatory pathways.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910831" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may affect antibody recognition and asprosin clearance.", "mechanism": "Targeting asprosin with antibodies improves hyperinsulinemia and metabolic syndrome in models.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10910831" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Glycosylation is required for asprosin's secretion and activity.", "mechanism": "Asprosin promotes hepatic glucose release and impairs insulin signaling, contributing to hyperglycemia and insulin resistance.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "causal", "source_pmcid": "PMC10910831" }, { "confidence": "low", "disease": "MAFLD", "glycan_involvement": "Glycosylation is necessary for asprosin's stability and function.", "mechanism": "Asprosin may promote MAFLD via insulin resistance and inflammation.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "causal", "source_pmcid": "PMC10910831" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation is essential for asprosin's secretion from adipose tissue.", "mechanism": "Asprosin deficiency leads to extreme leanness; high asprosin promotes weight gain.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "causal", "source_pmcid": "PMC10910831" }, { "confidence": "high", "disease": "Congenital tremor (type A-II)", "glycan_involvement": "High glycosylation of E2 is necessary for its immunogenicity and function.", "mechanism": "E2 is a major antigen of APPV, which is the main cause of congenital tremor in piglets.", "protein": "E2 protein (APPV)", "relationship_type": "causal", "source_pmcid": "PMC10910838" }, { "confidence": "high", "disease": "APPV infection", "glycan_involvement": "Glycosylation of E2 is required for correct folding and antigenicity.", "mechanism": "Antibodies against E2 serve as a biomarker for APPV infection in pigs.", "protein": "E2 protein (APPV)", "relationship_type": "biomarker", "source_pmcid": "PMC10910838" }, { "confidence": "medium", "disease": "High mortality in piglets", "glycan_involvement": "Glycosylation affects E2's ability to induce immune response.", "mechanism": "APPV infection, mediated by E2 glycoprotein, leads to high mortality in newborn piglets.", "protein": "E2 protein (APPV)", "relationship_type": "causal", "source_pmcid": "PMC10910838" }, { "confidence": "high", "disease": "Subclinical infection in adult pigs", "glycan_involvement": "Glycosylation ensures E2's antigenic similarity to native viral protein.", "mechanism": "Detection of anti-E2 antibodies indicates subclinical APPV infection.", "protein": "E2 protein (APPV)", "relationship_type": "biomarker", "source_pmcid": "PMC10910838" }, { "confidence": "medium", "disease": "APPV infection", "glycan_involvement": "Glycosylation may affect immunogenicity of E^rns.", "mechanism": "Antibodies against E^rns are used for serological detection of APPV.", "protein": "E^rns protein (APPV)", "relationship_type": "biomarker", "source_pmcid": "PMC10910838" }, { "confidence": "medium", "disease": "APPV infection", "glycan_involvement": "Not specified.", "mechanism": "Antibodies against NS3 are produced upon APPV infection.", "protein": "NS3 protein (APPV)", "relationship_type": "biomarker", "source_pmcid": "PMC10910838" }, { "confidence": "high", "disease": "APPV infection", "glycan_involvement": "Glycosylation is essential for E2's immunogenicity and vaccine efficacy.", "mechanism": "E2 is the major antigen inducing neutralizing antibodies, making it a potential vaccine target.", "protein": "E2 protein (APPV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10910838" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "NLRP3 is a glycoprotein; glycosylation may affect its stability and inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation promotes liver inflammation and injury via IL-1\u03b2 maturation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10910869" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "IL-1\u03b2 is glycosylated, which can affect secretion and activity.", "mechanism": "Elevated IL-1\u03b2 levels indicate hepatic inflammation and correlate with ALD severity.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910869" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "AMPK activation suppresses NLRP3 signaling, reduces inflammation, and promotes fatty acid oxidation.", "protein": "AMPK (PRKAA1/2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10910869" }, { "confidence": "high", "disease": "Acute Alcohol-induced Liver Injury (AALI)", "glycan_involvement": "Glycosylation may regulate NLRP3 function and inflammasome formation.", "mechanism": "NLRP3 activation drives acute inflammatory response and hepatocyte damage after binge alcohol exposure.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10910869" }, { "confidence": "high", "disease": "Acute Alcohol-induced Liver Injury (AALI)", "glycan_involvement": "Glycosylation affects IL-1\u03b2 secretion.", "mechanism": "Serum IL-1\u03b2 is increased in AALI and reduced by LanGui tea treatment.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910869" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "F4/80 is a glycoprotein; glycosylation is important for cell surface expression.", "mechanism": "F4/80 marks hepatic macrophage infiltration, indicating liver inflammation.", "protein": "F4/80 (EMR1)", "protein_enriched": { "function": "Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development", "gene_name": "Adgre1", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q61549" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910869" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Caspase-1 is not a glycoprotein; no direct glycan involvement.", "mechanism": "Caspase-1 activation by NLRP3 leads to IL-1\u03b2 maturation and hepatocyte pyroptosis.", "protein": "Caspase-1", "relationship_type": "causal", "source_pmcid": "PMC10910869" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "TNF\u03b1 is glycosylated, affecting stability and receptor binding.", "mechanism": "TNF\u03b1 upregulation reflects hepatic inflammation in ALD.", "protein": "TNF\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC10910869" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "MCP1 is glycosylated, influencing chemokine activity.", "mechanism": "MCP1 mediates monocyte recruitment to inflamed liver tissue.", "protein": "MCP1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC10910869" }, { "confidence": "medium", "disease": "Non-alcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may modulate NLRP3 inflammasome activity.", "mechanism": "NLRP3 activation contributes to NASH progression; inhibition is protective.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC10910869" }, { "confidence": "high", "disease": "Celiac disease", "glycan_involvement": "tTG is glycosylated; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Anti-tTG IgA antibodies are diagnostic for celiac disease.", "protein": "Tissue transglutaminase (tTG)", "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "high", "disease": "Vitamin B12 deficiency", "glycan_involvement": "Intrinsic factor is glycosylated, affecting stability and immune recognition.", "mechanism": "Anti-intrinsic factor antibodies indicate autoimmune B12 deficiency, often seen in celiac disease.", "protein": "Intrinsic factor", "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "medium", "disease": "Vitamin B12 deficiency", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Anti-parietal cell antibodies are associated with autoimmune gastritis and B12 deficiency.", "protein": "Parietal cell antigen", "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "Ferritin glycosylation affects serum stability and detection.", "mechanism": "Low ferritin reflects iron deficiency, common in celiac disease due to malabsorption.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "Transferrin glycosylation status can change in liver disease and inflammation.", "mechanism": "Low transferrin saturation is indicative of iron deficiency in celiac disease.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "medium", "disease": "Celiac disease", "glycan_involvement": "IgA glycosylation affects immune function and mucosal protection.", "mechanism": "IgA deficiency is a hematological manifestation of celiac disease.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "high", "disease": "Primary sclerosing cholangitis", "glycan_involvement": "ALP glycosylation affects enzyme activity and serum half-life.", "mechanism": "Elevated ALP is a hallmark of PSC, though may be normal in some cases.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "medium", "disease": "Primary sclerosing cholangitis", "glycan_involvement": "GGT glycosylation modulates enzyme activity.", "mechanism": "Elevated GGT is indicative of cholestatic liver disease such as PSC.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "low", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may affect tTG function in fibrogenesis.", "mechanism": "tTG activity may contribute to liver fibrosis in celiac disease.", "protein": "Tissue transglutaminase (tTG)", "relationship_type": "causal", "source_pmcid": "PMC10910874" }, { "confidence": "low", "disease": "Myelodysplastic syndrome", "glycan_involvement": "Altered glycosylation may impact immune surveillance.", "mechanism": "IgA deficiency may be present in MDS as a hematological manifestation of celiac disease.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC10910874" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and ligand binding.", "mechanism": "PD-1 is targeted by monoclonal antibodies to block immune checkpoint signaling, enhancing anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation modulates its cell surface expression and immune evasion.", "mechanism": "PD-L1 interacts with PD-1 to suppress T cell activity; blocking this interaction restores immune response against tumor.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "As a monoclonal antibody, glycosylation affects its efficacy and pharmacokinetics.", "mechanism": "Tislelizumab blocks PD-1, improving overall survival and objective response rate in unresectable HCC.", "protein": "Tislelizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Monoclonal antibody glycosylation impacts immune effector function.", "mechanism": "Nivolumab (anti-PD-1) improves efficacy and safety in advanced HCC, especially when combined with Ipilimumab.", "protein": "Nivolumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences antibody stability and immune activation.", "mechanism": "Pembrolizumab shows antitumor activity and safety in advanced HCC.", "protein": "Pembrolizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects antibody function and half-life.", "mechanism": "Sintilimab plus Bevacizumab biosimilar improves progression-free and overall survival in unresectable HCC.", "protein": "Sintilimab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Antibody glycosylation modulates therapeutic activity.", "mechanism": "Tislelizumab shows efficacy and safety in advanced/metastatic esophageal squamous cell carcinoma.", "protein": "Tislelizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "medium", "disease": "Nasopharyngeal cancer", "glycan_involvement": "Glycosylation impacts antibody function.", "mechanism": "Tislelizumab is effective in recurrent/metastatic nasopharyngeal cancer.", "protein": "Tislelizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "medium", "disease": "Advanced solid tumors", "glycan_involvement": "Glycosylation affects pharmacokinetics and immune response.", "mechanism": "Tislelizumab demonstrates efficacy and safety in advanced solid tumors.", "protein": "Tislelizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences antibody stability and immune modulation.", "mechanism": "Camrelizumab (anti-PD-1) is used as second-line therapy for progressive HCC.", "protein": "Camrelizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC10911588" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "HSD17B13 is a lipid droplet-associated glycoprotein; glycosylation may affect localization/function.", "mechanism": "Loss-of-function variants in HSD17B13 protect against progression to severe chronic liver disease.", "protein": "HSD17B13", "protein_enriched": { "function": "", "gene_name": "FAM174A", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G68008QO", "G81006GJ", "G04657PL", "G08918WF", "G80920RR" ], "uniprot_id": "Q8TBP5" }, "relationship_type": "protective", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may influence HSD17B13 stability and lipid droplet association.", "mechanism": "HSD17B13 is upregulated in NASH; ASO-mediated knockdown reduces hepatic steatosis but not fibrosis.", "protein": "HSD17B13", "protein_enriched": { "function": "", "gene_name": "FAM174A", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G68008QO", "G81006GJ", "G04657PL", "G08918WF", "G80920RR" ], "uniprot_id": "Q8TBP5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may modulate lipid droplet targeting.", "mechanism": "HSD17B13 knockdown reduces hepatic triglyceride accumulation and steatosis in mice.", "protein": "HSD17B13", "protein_enriched": { "function": "", "gene_name": "FAM174A", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G68008QO", "G81006GJ", "G04657PL", "G08918WF", "G80920RR" ], "uniprot_id": "Q8TBP5" }, "relationship_type": "causal", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "No direct evidence for glycan involvement in fibrosis modulation.", "mechanism": "ASO-mediated HSD17B13 knockdown does not affect hepatic fibrosis in CDAHFD mouse model.", "protein": "HSD17B13", "protein_enriched": { "function": "", "gene_name": "FAM174A", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G68008QO", "G81006GJ", "G04657PL", "G08918WF", "G80920RR" ], "uniprot_id": "Q8TBP5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10911849" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Binds \u03b2-galactoside glycans; glycosylation status of ligands affects function.", "mechanism": "Gal3 expression is elevated in fibrotic livers; used as a marker of inflammation/fibrosis.", "protein": "Galectin-3 (Gal3)", "protein_enriched": { "function": "Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration (PubMed:15181153). Together with DMBT1, required for te", "gene_name": "Lgals3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P16110" }, "relationship_type": "biomarker", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Collagens are N- and O-glycosylated, affecting fibril formation.", "mechanism": "Col1a1 upregulation marks increased extracellular matrix deposition in fibrosis.", "protein": "Collagen alpha-1(I) chain (Col1a1)", "relationship_type": "biomarker", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation modulates collagen stability.", "mechanism": "Col1a2 upregulation is associated with fibrotic matrix expansion.", "protein": "Collagen alpha-2(I) chain (Col1a2)", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08122" }, "relationship_type": "biomarker", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects collagen assembly.", "mechanism": "Col3a1 is upregulated in fibrotic liver tissue.", "protein": "Collagen alpha-1(III) chain (Col3a1)", "relationship_type": "biomarker", "source_pmcid": "PMC10911849" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "N-glycosylation affects PAI-1 secretion and activity.", "mechanism": "PAI-1 is upregulated in fibrosis, reflecting impaired matrix degradation.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10911849" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "N-glycosylation modulates TGF\u03b21 secretion and receptor binding.", "mechanism": "TGF\u03b21 drives fibrogenesis by activating hepatic stellate cells.", "protein": "Transforming growth factor beta-1 (TGF\u03b21)", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "Tgfb1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P04202" }, "relationship_type": "causal", "source_pmcid": "PMC10911849" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune evasion", "mechanism": "Spike mediates viral entry via ACE2 binding and membrane fusion", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "medium", "disease": "Long COVID (PASC)", "glycan_involvement": "Glycosylation affects spike persistence and immune recognition", "mechanism": "Persistent immune activation and tissue damage post-infection", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycans modulate spike-ACE2 interaction and immune response", "mechanism": "Spike-mediated infection triggers inflammation and fibrotic remodeling", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "medium", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation may affect spike-endothelial interactions", "mechanism": "Spike-induced endothelial activation and hyperinflammation promote clotting", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "medium", "disease": "Myocarditis/pericarditis", "glycan_involvement": "Glycans modulate immunogenicity of spike", "mechanism": "Immune response to spike protein can trigger cardiac inflammation", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "low", "disease": "Neuropsychiatric disorders (brain fog, anosmia)", "glycan_involvement": "Glycosylation may affect tissue tropism", "mechanism": "Spike-mediated infection of olfactory and neural tissues", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "low", "disease": "Alopecia areata", "glycan_involvement": "Not specified", "mechanism": "Post-infectious immune dysregulation", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (unclear)", "source_pmcid": "PMC10911975" }, { "confidence": "low", "disease": "Inflammatory arthritis", "glycan_involvement": "Not specified", "mechanism": "Post-infectious immune activation", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (possible trigger)", "source_pmcid": "PMC10911975" }, { "confidence": "low", "disease": "Acute renal damage", "glycan_involvement": "Glycosylation may affect tissue targeting", "mechanism": "Spike-mediated infection and inflammation in renal tissue", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10911975" }, { "confidence": "high", "disease": "COVID-19 (vaccine-induced immunity)", "glycan_involvement": "Glycosylation of recombinant spike affects antigenicity and immune response", "mechanism": "Vaccines use spike glycoprotein to elicit neutralizing antibodies", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10911975" }, { "confidence": "high", "disease": "Diabetic wound dysfunction", "glycan_involvement": "Notch1 is a glycoprotein; glycosylation modulates ligand binding and signaling.", "mechanism": "Activation of Notch1 signaling promotes angiogenesis, granulation tissue formation, and wound healing in diabetic rats.", "protein": "Notch1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912225" }, { "confidence": "high", "disease": "Diabetic wound dysfunction", "glycan_involvement": "Dll4 is glycosylated; glycosylation affects receptor interaction.", "mechanism": "Upregulation of Dll4 enhances Notch1 signaling, facilitating angiogenesis and wound repair.", "protein": "Dll4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetic wound dysfunction", "glycan_involvement": "Jagged1 is glycosylated; glycosylation influences Notch activation.", "mechanism": "Jagged1 upregulation by DBD activates Notch signaling, aiding wound healing.", "protein": "Jagged1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912225" }, { "confidence": "high", "disease": "Diabetic wound dysfunction", "glycan_involvement": "CD31 is heavily glycosylated; glycosylation affects cell adhesion and angiogenesis.", "mechanism": "Increased CD31 expression indicates enhanced angiogenesis in wound healing after DBD treatment.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetic wound dysfunction", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "Elevated IL-6 is associated with sustained inflammation and impaired wound healing; DBD reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetic wound dysfunction", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates activity.", "mechanism": "High TNF-\u03b1 correlates with inflammation and delayed healing; DBD lowers TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation of Notch1 regulates ligand specificity and signaling strength.", "mechanism": "Notch1 signaling is dysregulated in diabetes, contributing to impaired angiogenesis and wound healing.", "protein": "Notch1", "relationship_type": "causal", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Dll4 glycosylation modulates Notch1 interaction.", "mechanism": "Altered Dll4 expression in diabetes impairs Notch signaling and vascular repair.", "protein": "Dll4", "relationship_type": "causal", "source_pmcid": "PMC10912225" }, { "confidence": "medium", "disease": "Diabetic foot ulcer", "glycan_involvement": "Glycosylation of CD31 is essential for endothelial function.", "mechanism": "Reduced CD31 marks impaired angiogenesis in diabetic foot ulcers; DBD increases CD31.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912225" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Jagged1 glycosylation affects Notch pathway activation.", "mechanism": "Jagged1 dysregulation contributes to defective Notch signaling in diabetes.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC10912225" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "TLR4 is a glycoprotein receptor recognizing glycan-rich LPS.", "mechanism": "TLR4 activation by LPS induces hepatic inflammation and progression of MAFLD.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "FXR activity modulated by glycosylated bile acids.", "mechanism": "FXR activation regulates bile acid metabolism, reduces triglycerides, and ameliorates hepatic steatosis.", "protein": "FXR", "protein_enriched": { "function": "Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in", "gene_name": "NR1H4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96RI1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "TGR5 is a glycoprotein receptor for glycosylated bile acids.", "mechanism": "TGR5 activation improves insulin sensitivity and reduces obesity-related hepatic inflammation.", "protein": "TGR5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912229" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "SHP function is modulated by FXR, which binds glycosylated bile acids.", "mechanism": "SHP mediates FXR signaling to inhibit triglyceride synthesis.", "protein": "SHP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912229" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "SREBP-1c activity is regulated by FXR/SHP signaling involving glycosylated bile acids.", "mechanism": "SREBP-1c promotes hepatic lipogenesis, contributing to MAFLD.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10912229" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "PPAR-\u03b1 expression is upregulated by FXR activation via glycosylated bile acids.", "mechanism": "PPAR-\u03b1 activation promotes lipid oxidation and reduces hepatic fat accumulation.", "protein": "PPAR-\u03b1", "protein_enriched": { "function": "Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethano", "gene_name": "PPARA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07869" }, "relationship_type": "protective", "source_pmcid": "PMC10912229" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "CYP7A1 activity is modulated by FXR/TGR5 signaling involving glycosylated bile acids.", "mechanism": "CYP7A1 regulates bile acid synthesis; inhibition by FXR/TGR5 reduces hepatic bile acid overload.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "ZO-1 is a glycoprotein essential for tight junctions.", "mechanism": "ZO-1 maintains gut barrier integrity, reducing LPS translocation and hepatic inflammation.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Occludin is a glycoprotein involved in tight junctions.", "mechanism": "Occludin supports gut barrier function, limiting LPS-induced liver injury.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Claudin1 is a glycoprotein component of tight junctions.", "mechanism": "Claudin1 strengthens gut barrier, reducing endotoxin leakage and hepatic inflammation.", "protein": "Claudin1", "relationship_type": "protective", "source_pmcid": "PMC10912229" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Lumican is a proteoglycan with glycosaminoglycan chains that modulate ECM structure.", "mechanism": "Elevated lumican levels in hepatic tissue and serum correlate with advanced fibrosis severity.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects lumican's ECM interactions and fibrogenic signaling.", "mechanism": "Modulates ECM composition and fibrotic progression in NAFLD; Qiyin intervention normalizes lumican levels.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912341" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Decorin's glycosaminoglycan chains are essential for TGF-\u03b2 binding and antifibrotic activity.", "mechanism": "Decorin sequesters TGF-\u03b2, inhibiting profibrogenic signaling and reducing fibrosis.", "protein": "Decorin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912341" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates decorin's ECM and cytokine interactions.", "mechanism": "Qiyin intervention restores decorin levels, attenuating liver inflammation and fibrosis in NAFLD.", "protein": "Decorin", "relationship_type": "protective", "source_pmcid": "PMC10912341" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Desmin is glycosylated, which may affect filament stability and cellular stress response.", "mechanism": "Desmin expression is elevated in NAFLD and reduced by Qiyin, indicating its role in hepatic injury and fibrosis.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Potential O-glycosylation may regulate actin-binding and cellular localization.", "mechanism": "Tagln is upregulated in NAFLD and normalized by Qiyin, reflecting cytoskeletal remodeling in disease.", "protein": "Transgelin (Tagln)", "protein_enriched": { "function": "", "gene_name": "GATA-6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9WUZ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may influence actin filament stability.", "mechanism": "Tpm2 is increased in NAFLD and reduced by Qiyin, indicating involvement in cytoskeletal changes.", "protein": "Tropomyosin beta chain (Tpm2)", "protein_enriched": { "function": "Binds to actin filaments in muscle and non-muscle cells (PubMed:22812662, PubMed:7568216). Plays a central role, in association with the troponin complex, in the calcium dependent regulation of verteb", "gene_name": "Tpm2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P58775" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect motor activity and ECM interactions.", "mechanism": "Myh11 is upregulated in NAFLD and normalized by Qiyin, associated with contractile function in hepatic stellate cells.", "protein": "Myosin-11 (Myh11)", "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosaminoglycan chains modulate cell signaling and tumor microenvironment.", "mechanism": "Altered lumican expression is implicated in ECM remodeling and tumor progression in HCC.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912341" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation is critical for decorin's tumor-suppressive functions.", "mechanism": "Decorin inhibits tumor growth by antagonizing TGF-\u03b2 and modulating ECM.", "protein": "Decorin", "relationship_type": "protective", "source_pmcid": "PMC10912341" }, { "confidence": "high", "disease": "Relapsing-remitting multiple sclerosis (RRMS)", "glycan_involvement": "CD52 is a glycoprotein; glycosylation is essential for its cell surface expression and antibody recognition.", "mechanism": "Alemtuzumab targets CD52 on lymphocytes, leading to their depletion and immunomodulation in RRMS.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912463" }, { "confidence": "high", "disease": "Relapsing-remitting multiple sclerosis (RRMS)", "glycan_involvement": "Alemtuzumab is glycosylated, which affects its stability and effector functions.", "mechanism": "Alemtuzumab binds CD52, depleting T and B cells via complement and antibody-dependent cytolysis, reducing MS activity.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "therapeutic", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Non-immune thrombocytopenia", "glycan_involvement": "CD52 glycosylation is required for antibody binding and cell depletion.", "mechanism": "Alemtuzumab-induced cytolysis of CD52-expressing cells leads to transient thrombocytopenia.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Infusion-associated reactions (IARs)", "glycan_involvement": "Glycosylation of CD52 may influence antibody binding and immune response.", "mechanism": "Alemtuzumab binding to CD52 triggers cytokine release and immune activation, causing IARs (rash, headache, fever).", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Autoimmune thyroid pathology", "glycan_involvement": "Glycosylation status may affect immune recognition and tolerance.", "mechanism": "Long-term lymphocyte depletion and immune reconstitution after CD52 targeting can trigger secondary autoimmunity (thyroid).", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "low", "disease": "Autoimmune kidney pathology", "glycan_involvement": "Glycosylation may modulate immune cell interactions.", "mechanism": "Immune dysregulation post-CD52 depletion may lead to renal autoimmunity.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Infusion-associated reactions (IARs)", "glycan_involvement": "Glycosylation of Alemtuzumab affects Fc-mediated effector functions and immune activation.", "mechanism": "Alemtuzumab administration causes cytokine release syndrome and IARs.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "low", "disease": "Shingles (varicella-zoster virus infection)", "glycan_involvement": "Glycosylation may affect immune surveillance.", "mechanism": "CD52-targeted lymphocyte depletion increases susceptibility to viral infections.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Non-immune thrombocytopenia", "glycan_involvement": "Glycosylation impacts Alemtuzumab's pharmacodynamics.", "mechanism": "Alemtuzumab-induced cytokine release and immune cell depletion cause transient thrombocytopenia.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "medium", "disease": "Autoimmune thyroid pathology", "glycan_involvement": "Glycosylation may modulate immunogenicity.", "mechanism": "Alemtuzumab-induced immune reconstitution can trigger thyroid autoimmunity.", "protein": "Alemtuzumab", "protein_enriched": { "function": "O-methyltransferase required for two non-consecutive steps during ubiquinone biosynthesis (By similarity) (PubMed:10777520, PubMed:38425362). Catalyzes the 2 O-methylation of 3,4-dihydroxy-5-(all-tran", "gene_name": "COQ3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NZJ6" }, "relationship_type": "causal", "source_pmcid": "PMC10912463" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation of EGF-like repeats modulates ligand binding and activation.", "mechanism": "Promotes tumor immunosuppression via MDSC recruitment and supports cancer stemness through crosstalk with STAT3.", "protein": "Notch1", "relationship_type": "causal", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Triple negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation affects ligand-receptor interaction strength.", "mechanism": "Jag1-mediated Notch signaling recruits TAMs and suppresses CD8+ T cell function, promoting immune evasion.", "protein": "Jagged1 (Jag1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-glycosylation of EGF-like domains regulates receptor activation.", "mechanism": "Increases cytokine expression (CCL2, CSF-1, CXCL12) to recruit immunosuppressive macrophages and MDSCs.", "protein": "Notch3", "relationship_type": "causal", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Tumor angiogenesis (multiple cancers)", "glycan_involvement": "Glycosylation modulates ligand presentation and function.", "mechanism": "Highly expressed in tumor vasculature; targeting Dll4 disrupts angiogenesis and overcomes VEGF resistance.", "protein": "Dll4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "O-glycosylation required for proper receptor function and immune modulation.", "mechanism": "Activation increases MHC-I and IFN-\u03b3-dependent cytokines, recruiting antitumor CD8+ T cells.", "protein": "Notch1", "relationship_type": "protective", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "Glycosylation influences ligand stability and targeting.", "mechanism": "Targeted by antibody-drug conjugate Rova-T for cytotoxicity against Dll3-expressing SCLC cells.", "protein": "Dll3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Chronic lymphocytic leukemia (CLL)", "glycan_involvement": "Glycosylation of Notch1 affects receptor signaling and immune escape.", "mechanism": "Decreases HLA class II expression and increases PD-L1, promoting immune evasion and T cell exhaustion.", "protein": "Notch1", "relationship_type": "causal", "source_pmcid": "PMC10912471" }, { "confidence": "medium", "disease": "B cell lymphoma", "glycan_involvement": "Glycosylation modulates ligand-receptor specificity.", "mechanism": "Jag2-induced Notch signaling enhances DC-mediated NK and cytotoxic T cell activity, suppressing tumor growth.", "protein": "Jagged2 (Jag2)", "protein_enriched": { "function": "Putative Notch ligand involved in the mediation of Notch signaling. Involved in limb development (By similarity)", "gene_name": "JAG2", "glycan_count": 2, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G83460ZZ", "G80920RR" ], "uniprot_id": "Q9Y219" }, "relationship_type": "protective", "source_pmcid": "PMC10912471" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation status may influence mutation effects.", "mechanism": "Notch4 mutation correlates with increased immunogenicity and better response to immune checkpoint inhibitors.", "protein": "Notch4", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it for", "gene_name": "NOTCH4", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G71142DF", "G53434XO", "G58001LT" ], "uniprot_id": "Q99466" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912471" }, { "confidence": "medium", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "CD44 is a heavily glycosylated protein; glycosylation affects cell adhesion and immune modulation.", "mechanism": "Notch activation in endothelial cells upregulates CD44 in TAMs, promoting immunosuppressive microenvironment.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10912471" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation affects integrin conformation and ligand binding.", "mechanism": "\u03b14\u03b27 mediates lymphocyte homing to gut via MAdCAM-1; blockade reduces gut inflammation.", "protein": "\u03b14\u03b27 integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation modulates integrin-ligand interactions.", "mechanism": "Targeted by vedolizumab to block lymphocyte trafficking to inflamed gut.", "protein": "\u03b14\u03b27 integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation of gp120 and integrin influences binding.", "mechanism": "\u03b14\u03b27 binds HIV gp120, facilitating viral entry and cell-to-cell spread.", "protein": "\u03b14\u03b27 integrin", "relationship_type": "causal", "source_pmcid": "PMC10912472" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation affects receptor surface expression and function.", "mechanism": "CCR5 acts as HIV co-receptor; blockade prevents viral entry.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "CCR5+ cells and ligands found in inflamed synovial fluid; blockade reduces inflammation.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation influences receptor trafficking.", "mechanism": "CCR5+ cells contribute to CNS inflammation; blockade may reduce neuroinflammation.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects receptor function and migration.", "mechanism": "CCR6+ cells migrate to CNS via CCL20; elevated in MS CSF.", "protein": "CCR6", "protein_enriched": { "function": "Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is ", "gene_name": "CCR6", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51684" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Glycosylation regulates integrin binding to E-cadherin.", "mechanism": "CD103+ T cells interact with E-cadherin, promoting intraepithelial localization in gut inflammation.", "protein": "CD103 (\u03b1E integrin)", "protein_enriched": { "function": "May play a role in an as yet undefined retina-specific signal transduction. Could bind to photoactivated-phosphorylated red/green opsins", "gene_name": "ARR3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P36575" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation critical for ligand recognition.", "mechanism": "MAdCAM-1 binds \u03b14\u03b27, mediating lymphocyte recruitment to inflamed gut.", "protein": "MAdCAM-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates PD-1 surface expression and function.", "mechanism": "PD-1 regulates immune tolerance; blockade enhances anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912472" }, { "confidence": "high", "disease": "MEGDHEL syndrome", "glycan_involvement": "Potential indirect effect on glycoprotein processing via mitochondrial dysfunction.", "mechanism": "SERAC1 deficiency disrupts phosphatidylglycerol remodeling, affecting mitochondrial function and cholesterol trafficking, leading to MEGDHEL syndrome.", "protein": "SERAC1", "protein_enriched": { "function": "Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear pol", "gene_name": "TENT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PIY7" }, "relationship_type": "causal", "source_pmcid": "PMC10912554" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "Possible disruption of glycoprotein synthesis in hepatocytes due to mitochondrial dysfunction.", "mechanism": "SERAC1 mutations impair liver synthesis and mitochondrial energy metabolism, resulting in acute liver failure in neonates.", "protein": "SERAC1", "protein_enriched": { "function": "Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear pol", "gene_name": "TENT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PIY7" }, "relationship_type": "causal", "source_pmcid": "PMC10912554" }, { "confidence": "high", "disease": "Hyperammonemia", "glycan_involvement": "Indirect; mitochondrial dysfunction may affect glycoprotein enzymes involved in ammonia metabolism.", "mechanism": "SERAC1 deficiency impairs hepatic ammonia detoxification, leading to hyperammonemia.", "protein": "SERAC1", "protein_enriched": { "function": "Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear pol", "gene_name": "TENT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PIY7" }, "relationship_type": "causal", "source_pmcid": "PMC10912554" }, { "confidence": "high", "disease": "3-methylglutaconic aciduria", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "SERAC1 mutations cause accumulation of 3-methylglutaconic acid due to mitochondrial dysfunction.", "protein": "SERAC1", "protein_enriched": { "function": "Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear pol", "gene_name": "TENT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6PIY7" }, "relationship_type": "causal", "source_pmcid": "PMC10912554" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation is essential for coagulation factor stability and function.", "mechanism": "Reduced synthesis of glycosylated coagulation factors is a marker of liver failure.", "protein": "Coagulation factors", "relationship_type": "biomarker", "source_pmcid": "PMC10912554" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Transaminases are glycoproteins; glycosylation affects their secretion and stability.", "mechanism": "Normal transaminase levels despite liver failure suggest non-classical hepatic injury in MEGDHEL syndrome.", "protein": "Transaminases (AST, ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC10912554" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "ABCC2 is a glycoprotein; glycosylation may affect transporter function and metabolite handling.", "mechanism": "Polymorphisms in ABCC2 affect flavanone metabolite excretion, influencing polyphenol bioavailability and potential cardiovascular protection.", "protein": "ABCC2 (MRP2)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compoun", "gene_name": "ABCC2", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G59324HL" ], "uniprot_id": "Q92887" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "SULT1A1 is glycosylated; glycosylation may influence enzyme stability and activity.", "mechanism": "SULT1A1 polymorphisms modulate sulfate conjugation of flavanones, impacting metabolite excretion and cardiovascular effects.", "protein": "SULT1A1", "protein_enriched": { "function": "Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine group", "gene_name": "SULT1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50225" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "SULT1C4 is glycosylated; glycosylation may affect function.", "mechanism": "SULT1C4 variants affect sulfate conjugation of flavanones, altering bioavailability and cardiovascular benefit.", "protein": "SULT1C4", "protein_enriched": { "function": "Atypical sulfotransferase family member with very low affinity for 3'-phospho-5'-adenylyl sulfate (PAPS) and very low catalytic activity towards L-triiodothyronine, thyroxine, estrone, p-nitrophenol, ", "gene_name": "SULT4A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BR01" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "OATP1B1 is glycosylated; glycosylation may modulate transporter activity.", "mechanism": "Genetic variation in OATP1B1 influences uptake of polyphenol metabolites, affecting systemic exposure and cardiovascular outcomes.", "protein": "OATP1B1 (SLCO1B1)", "protein_enriched": { "function": "Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taur", "gene_name": "SLCO1B1", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G34989PA", "G90659AW" ], "uniprot_id": "Q9Y6L6" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "P-glycoprotein is highly glycosylated; glycosylation is critical for function.", "mechanism": "Polymorphisms in P-glycoprotein affect polyphenol absorption and disposition, influencing cardiovascular risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "UGTs are glycoproteins; glycosylation may affect enzyme localization and activity.", "mechanism": "UGT polymorphisms alter glucuronidation of flavanones, impacting metabolite profile and cardiovascular effects.", "protein": "UDP-glucuronosyltransferase (UGT)", "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Colorectal cancer", "glycan_involvement": "CYP1A1 is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "CYP1A1 polymorphisms may affect demethylation of polymethoxyflavones, influencing metabolite profiles linked to cancer risk.", "protein": "CYP1A1", "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Colorectal cancer", "glycan_involvement": "CYP2A6 is glycosylated; glycosylation may affect function.", "mechanism": "CYP2A6 variants may influence polyphenol metabolism, impacting metabolite profiles relevant to cancer risk.", "protein": "CYP2A6", "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation may regulate transporter function.", "mechanism": "ABCC2 polymorphisms affect excretion of polyphenol metabolites, which may modulate metabolic syndrome risk.", "protein": "ABCC2 (MRP2)", "protein_enriched": { "function": "ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compoun", "gene_name": "ABCC2", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G59324HL" ], "uniprot_id": "Q92887" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "SULT1A1 variants influence sulfate conjugation of polyphenols, potentially affecting obesity-related metabolic outcomes.", "protein": "SULT1A1", "protein_enriched": { "function": "Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine group", "gene_name": "SULT1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50225" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912651" }, { "confidence": "high", "disease": "Kidney transplant rejection", "glycan_involvement": "Glycosylation of \u03b1-1-acid glycoprotein modulates drug binding and distribution.", "mechanism": "Tacrolimus binds strongly to \u03b1-1-acid glycoprotein, affecting its pharmacokinetics and immunosuppressive efficacy.", "protein": "\u03b1-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "high", "disease": "Kidney transplant rejection", "glycan_involvement": "No direct glycan involvement in tacrolimus-FKBP12 complex, but downstream targets may be glycoproteins.", "mechanism": "Tacrolimus inhibits calcineurin via FKBP12, suppressing T-cell activation and preventing rejection.", "protein": "Tacrolimus (FK506-binding protein 12 complex)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912931" }, { "confidence": "high", "disease": "Antibody-mediated rejection", "glycan_involvement": "HLA glycosylation affects antigenicity and antibody binding.", "mechanism": "DSAs target HLA glycoproteins on graft cells, leading to antibody-mediated rejection.", "protein": "Human leukocyte antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC10912931" }, { "confidence": "high", "disease": "Antibody-mediated rejection", "glycan_involvement": "DSA glycosylation modulates effector functions and complement activation.", "mechanism": "Presence of DSAs correlates with risk of antibody-mediated rejection.", "protein": "Donor-specific antibody (DSA)", "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "medium", "disease": "Nephrotoxicity", "glycan_involvement": "Albumin glycosylation may affect drug binding.", "mechanism": "Tacrolimus binds to serum albumin, influencing free drug levels and risk of nephrotoxicity.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "medium", "disease": "Kidney transplant rejection", "glycan_involvement": "Some NFAT target genes encode glycoproteins involved in immune signaling.", "mechanism": "Residual NFAT-regulated gene expression reflects immunosuppressive efficacy and risk of rejection.", "protein": "NFAT-regulated gene products", "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "medium", "disease": "Opportunistic infections", "glycan_involvement": "CRP glycosylation affects its immune functions.", "mechanism": "Elevated CRP indicates inflammation or infection, which may be linked to immunosuppressive therapy.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "medium", "disease": "T-cell-mediated rejection", "glycan_involvement": "IL-2R glycosylation modulates receptor function and antibody binding.", "mechanism": "IL-2R antagonists are used to prevent T-cell-mediated rejection.", "protein": "Interleukin-2 receptor (IL-2R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10912931" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Cystatin C is glycosylated, affecting its stability and clearance.", "mechanism": "Cystatin C levels are used to estimate glomerular filtration rate (eGFR) and monitor kidney function.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Diabetes alters glycan structures on \u03b1-1-acid glycoprotein.", "mechanism": "Altered glycosylation of \u03b1-1-acid glycoprotein is associated with diabetes and may affect tacrolimus pharmacokinetics.", "protein": "\u03b1-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC10912931" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Not directly discussed; ALT may be glycosylated but not mechanistically linked in this study.", "mechanism": "Elevated ALT reflects liver fat accumulation and hepatic insulin resistance, increasing T2D risk.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "GGT is a glycoprotein; glycosylation required for activity but not mechanistically linked in this study.", "mechanism": "Elevated GGT is associated with oxidative stress and chronic inflammation, contributing to insulin resistance and T2D development.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Not directly discussed; AST may be glycosylated but not mechanistically linked in this study.", "mechanism": "AST shows a non-linear association; mildly elevated AST may increase T2D risk, but higher levels are protective.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC10913017" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Not discussed.", "mechanism": "ALT is associated with liver fat accumulation and used as a surrogate marker for NAFLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "GGT is a glycoprotein; glycosylation required for activity but not mechanistically linked in this study.", "mechanism": "GGT is related to obesity, dyslipidemia, and hypertension, components of metabolic syndrome.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Not discussed.", "mechanism": "Elevated GGT indicates liver dysfunction and is associated with NAFLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Not discussed.", "mechanism": "ALT elevation is associated with metabolic syndrome features via hepatic insulin resistance.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "GGT glycosylation required for activity; not mechanistically linked in this study.", "mechanism": "GGT elevation reflects oxidative stress and inflammation, which damage insulin signaling and promote T2D.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "causal (suggested)", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Not discussed.", "mechanism": "ALT elevation reflects hepatic insulin resistance, contributing to increased hepatic glucose production and T2D.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "causal (suggested)", "source_pmcid": "PMC10913017" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Not discussed.", "mechanism": "AST elevation indicates liver injury, a feature of NAFLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913017" }, { "confidence": "high", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation affects GPIb-IX-V structure and function.", "mechanism": "Deficiency or dysfunction of GPIb-IX-V impairs platelet adhesion to vWF/collagen, causing bleeding.", "protein": "Glycoprotein Ib-IX-V complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10913127" }, { "confidence": "high", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "vWF glycosylation modulates binding affinity.", "mechanism": "vWF binding to GPIb-IX-V is essential for platelet adhesion; impaired in BSS.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation influences GPIb-IX-V stability and platelet lifespan.", "mechanism": "Defective GPIb-IX-V leads to abnormal platelet morphology and reduced count.", "protein": "Glycoprotein Ib-IX-V complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation required for FVIIa activity and stability.", "mechanism": "Recombinant FVIIa used to enhance coagulation in BSS patients.", "protein": "Factor VII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation affects plasminogen activation and inhibitor binding.", "mechanism": "Antifibrinolytics (TXA) block plasminogen activation, reducing bleeding.", "protein": "Plasminogen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Glycosylation modulates fibrinogen function.", "mechanism": "Cryoprecipitate (rich in fibrinogen) used to support clot formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Hemorrhagic shock", "glycan_involvement": "Loss of glycosylation may exacerbate dysfunction.", "mechanism": "Severe GPIb-IX-V dysfunction leads to uncontrolled bleeding and shock.", "protein": "Glycoprotein Ib-IX-V complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10913127" }, { "confidence": "high", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Altered glycosylation can be detected in diagnostic assays.", "mechanism": "GPIb-IX-V deficiency/dysfunction is diagnostic for BSS.", "protein": "Glycoprotein Ib-IX-V complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Hemorrhagic shock", "glycan_involvement": "Glycosylation is critical for vWF function.", "mechanism": "vWF supports platelet adhesion; deficiency or impaired interaction increases bleeding risk.", "protein": "von Willebrand factor (vWF)", "relationship_type": "protective", "source_pmcid": "PMC10913127" }, { "confidence": "high", "disease": "Bernard-Soulier syndrome (BSS)", "glycan_involvement": "Transfused platelets must have intact glycosylation for efficacy.", "mechanism": "Platelet transfusions provide functional GPIb-IX-V to restore hemostasis.", "protein": "Glycoprotein Ib-IX-V complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913127" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "E-cadherin function and stability depend on N-glycosylation; disruption may affect adhesion.", "mechanism": "Loss of E-cadherin-mediated cell-cell adhesion observed after GNB exposure, indicating membrane/cytoskeletal damage.", "protein": "E-cadherin (E-cad)", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "Cdh1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09803" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "ZO-1 is glycosylated; glycan changes can modulate tight junction integrity.", "mechanism": "Disruption of ZO-1 localization in Hep-orgs after GNB exposure reflects tight junction breakdown.", "protein": "Zona occludens-1 (ZO-1)", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "CK19 is O-glycosylated; glycosylation affects filament assembly and stability.", "mechanism": "Altered CK19 expression in organoids after GNB exposure indicates epithelial injury.", "protein": "Cytokeratin 19 (CK19)", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "ALB is N-glycosylated; glycosylation affects secretion and stability.", "mechanism": "Increased serum ALB after GNB exposure indicates hepatocyte injury and leakage.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "low", "disease": "Hepatotoxicity", "glycan_involvement": "AFP is N-glycosylated; glycan changes are associated with liver injury.", "mechanism": "AFP expression used to confirm hepatocyte identity in organoids; not directly linked to toxicity in this study.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "low", "disease": "Hepatotoxicity", "glycan_involvement": "EPCAM is N-glycosylated; glycosylation modulates cell adhesion.", "mechanism": "EPCAM expression marks epithelial integrity; altered in organoids after GNB exposure.", "protein": "EPCAM", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "low", "disease": "Lipid degeneration (hepatic steatosis)", "glycan_involvement": "N-glycosylation of ALB may be altered in steatotic cells.", "mechanism": "ALB synthesis affected in lipid-laden hepatocytes after GNB exposure.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC10913213" }, { "confidence": "medium", "disease": "Polymyalgia rheumatica (PMR)", "glycan_involvement": "Spike glycoprotein's glycosylation modulates immunogenicity and immune activation.", "mechanism": "Immune response to spike glycoprotein expressed by mRNA vaccine may trigger PMR via innate immune activation.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10913505" }, { "confidence": "high", "disease": "Polymyalgia rheumatica (PMR)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP levels indicate inflammation and disease activity in PMR.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10913505" }, { "confidence": "medium", "disease": "Polymyalgia rheumatica (PMR)", "glycan_involvement": "Ferritin glycosylation may affect serum stability.", "mechanism": "Serum ferritin measured as part of inflammatory assessment in PMR.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913505" }, { "confidence": "medium", "disease": "Polymyalgia rheumatica (PMR)", "glycan_involvement": "HLA glycosylation modulates antigen presentation and immune response.", "mechanism": "Genetic HLA typing associated with PMR susceptibility.", "protein": "Human leukocyte antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC10913505" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation shields spike from immune recognition and affects infectivity.", "mechanism": "Spike glycoprotein mediates viral entry and infection.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10913505" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 1", "glycan_involvement": "Non-enzymatic glycation (Amadori rearrangement) of hemoglobin.", "mechanism": "Reflects chronic glycemic control via non-enzymatic glycation of hemoglobin.", "protein": "HbA1c (Glycated Hemoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "Non-enzymatic glycation (Amadori rearrangement) of hemoglobin.", "mechanism": "Reflects chronic glycemic control via non-enzymatic glycation of hemoglobin.", "protein": "HbA1c (Glycated Hemoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 1", "glycan_involvement": "Non-enzymatic glycation of multiple proteins.", "mechanism": "AGEs accumulate due to hyperglycemia, contributing to tissue damage and complications.", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "Non-enzymatic glycation of multiple proteins.", "mechanism": "AGEs accumulate due to hyperglycemia, contributing to tissue damage and complications.", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10913560" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Non-enzymatic glycation of extracellular matrix proteins.", "mechanism": "AGEs correlate with liver stiffness and may promote fibrosis via ROS induction.", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10913560" }, { "confidence": "medium", "disease": "Liver Steatosis (Fatty Liver)", "glycan_involvement": "Non-enzymatic glycation of hepatic proteins.", "mechanism": "AGEs correlate with hepatic fat accumulation (CAP values).", "protein": "Advanced Glycation End-products (AGEs)", "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "GDF15 is a glycoprotein; glycosylation may affect secretion/stability.", "mechanism": "Elevated GDF15 reflects metabolic stress and correlates with SAGEs.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 1", "glycan_involvement": "GDF15 is a glycoprotein; glycosylation may affect secretion/stability.", "mechanism": "Elevated GDF15 reflects metabolic stress and correlates with SAGEs.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "medium", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect activity.", "mechanism": "FGF21 is elevated in DM2, involved in energy homeostasis and may have hepatoprotective effects.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10913560" }, { "confidence": "medium", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "IGFBP3 is a glycoprotein; glycosylation may affect IGF binding.", "mechanism": "IGFBP3 levels are reduced in DM2 and negatively correlate with SAGEs.", "protein": "IGFBP3", "relationship_type": "biomarker", "source_pmcid": "PMC10913560" }, { "confidence": "high", "disease": "Chronic equine piroplasmosis", "glycan_involvement": "Parasite glycoproteins are essential for host cell recognition and immune modulation.", "mechanism": "T. equi glycoproteins mediate erythrocyte invasion and immune evasion, causing persistent infection.", "protein": "Theileria equi surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Chronic equine piroplasmosis", "glycan_involvement": "Globulins are glycoproteins; glycosylation affects their immune function.", "mechanism": "Serum globulin levels are altered in infected horses, reflecting immune response.", "protein": "Globulins", "relationship_type": "biomarker", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Chronic equine piroplasmosis", "glycan_involvement": "GGT is a glycoprotein; glycosylation may affect stability and activity.", "mechanism": "GGT activity is altered in infected horses, indicating possible liver involvement.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Chronic equine piroplasmosis", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates enzyme activity.", "mechanism": "ALP activity is altered in infected horses, possibly reflecting tissue damage.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913582" }, { "confidence": "low", "disease": "Chronic equine piroplasmosis", "glycan_involvement": "AST may be glycosylated; glycosylation can affect secretion and stability.", "mechanism": "AST levels are altered in infected horses, indicating muscle or liver involvement.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Inflammatory myopathy", "glycan_involvement": "Parasite glycoproteins may act as antigens or molecular mimics.", "mechanism": "Chronic T. equi infection triggers autoimmune response against muscle antigens.", "protein": "Theileria equi surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Perivasculitis", "glycan_involvement": "Glycoprotein antigens may drive immune complex formation.", "mechanism": "Chronic infection leads to vascular inflammation, possibly via immune complexes.", "protein": "Theileria equi surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913582" }, { "confidence": "low", "disease": "Inflammatory myopathy", "glycan_involvement": "Glycosylation modulates globulin function in immunity.", "mechanism": "Altered globulin levels reflect ongoing immune response in muscle inflammation.", "protein": "Globulins", "relationship_type": "biomarker", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Muscle atrophy", "glycan_involvement": "Glycoprotein antigens may trigger autoimmunity.", "mechanism": "Chronic infection and immune-mediated myopathy contribute to muscle loss.", "protein": "Theileria equi surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913582" }, { "confidence": "medium", "disease": "Poor performance syndrome", "glycan_involvement": "Glycoprotein-mediated immune evasion and inflammation.", "mechanism": "Chronic infection may contribute to subclinical muscle and vascular changes affecting performance.", "protein": "Theileria equi surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913582" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity and stability.", "mechanism": "CRP induces pro-inflammatory effects on endothelial cells, leading to dysfunction.", "protein": "C-reactive protein", "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used to diagnose and monitor diabetes.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC10913653" }, { "confidence": "high", "disease": "Arterial stiffness", "glycan_involvement": "Non-enzymatic glycation alters protein structure and function.", "mechanism": "AGEs accumulate in vessel walls, crosslinking collagen/elastin and increasing stiffness.", "protein": "Advanced glycation end products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "high", "disease": "Arterial stiffness", "glycan_involvement": "AGE formation on collagen disrupts normal glycosylation and crosslinking.", "mechanism": "Glycation and remodeling of collagen reduce arterial elasticity.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "high", "disease": "Arterial stiffness", "glycan_involvement": "AGE modification impairs elastin's normal glycosylation and function.", "mechanism": "Glycation and breakdown of elastin decrease arterial compliance.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "Glycosylation affects eNOS localization and activity.", "mechanism": "Impaired eNOS activity reduces NO bioavailability, promoting stiffness.", "protein": "Endothelial nitric oxide synthase (eNOS)", "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Altered glycosylation impairs receptor function and signaling.", "mechanism": "Defective insulin receptor signaling leads to insulin resistance.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation regulates VCAM-1's cell surface expression and binding.", "mechanism": "VCAM-1 mediates leukocyte adhesion, promoting vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ICAM-1's adhesive properties.", "mechanism": "ICAM-1 facilitates leukocyte transmigration, contributing to plaque formation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation is essential for LDLR folding and function.", "mechanism": "LDLR regulates cholesterol uptake; dysfunction leads to dyslipidemia.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "causal", "source_pmcid": "PMC10913653" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "HBV glycoproteins' glycosylation may facilitate immune recognition and mimicry.", "mechanism": "Molecular mimicry between HBV glycoproteins and myelin antigens triggers autoimmunity against peripheral nerve myelin.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "causal", "source_pmcid": "PMC10913701" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation of P0 may affect antigenicity and immune targeting.", "mechanism": "Autoantibodies and T cells cross-react with P0 due to molecular mimicry, leading to demyelination.", "protein": "Myelin Protein Zero (P0)", "relationship_type": "causal", "source_pmcid": "PMC10913701" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation status may modulate immune recognition.", "mechanism": "Immune cross-reactivity with PMP22 following HBV infection contributes to nerve damage.", "protein": "Peripheral Myelin Protein 22 (PMP22)", "protein_enriched": { "function": "Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormon", "gene_name": "CACNA1D", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G83460ZZ", "G11541NC", "G49108TO" ], "uniprot_id": "Q01668" }, "relationship_type": "causal", "source_pmcid": "PMC10913701" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "Autoimmune response against P2 induced by HBV-related molecular mimicry.", "protein": "Myelin Protein P2", "protein_enriched": { "function": "May play a role in lipid transport protein in Schwann cells. May bind cholesterol", "gene_name": "PMP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02689" }, "relationship_type": "causal", "source_pmcid": "PMC10913701" }, { "confidence": "high", "disease": "Hepatitis B infection", "glycan_involvement": "Glycosylation affects antigen stability and immune detection.", "mechanism": "HBeAg presence indicates active HBV replication and infectivity.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913701" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect its filtration and detection.", "mechanism": "Urinary albumin (microalbuminuria) is a classical marker for DKD diagnosis and progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "LDHA is glycosylated; glycosylation may modulate enzyme stability and localization.", "mechanism": "Renal LDHA-mediated lactic acidosis leads to fibrosis and mitochondrial abnormalities in DKD; targeting LDHA improves DKD outcomes.", "protein": "Lactate dehydrogenase A (LDHA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913800" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Glycosylation status may affect LDHA secretion and activity.", "mechanism": "Elevated LDHA and lactate levels in serum, urine, and kidney tissue are early biomarkers for DKD.", "protein": "Lactate dehydrogenase A (LDHA)", "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion and aggregation; altered glycosylation may enhance pro-inflammatory responses.", "mechanism": "Increased platelet count and activation are associated with DKD risk and progression.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "medium", "disease": "End-Stage Kidney Disease (ESKD)", "glycan_involvement": "Glycosylation may influence albumin's renal handling.", "mechanism": "Persistent albuminuria predicts progression to ESKD in diabetic patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "low", "disease": "End-Stage Kidney Disease (ESKD)", "glycan_involvement": "Glycosylation may affect LDHA's renal localization.", "mechanism": "Higher LDHA levels correlate with worse renal function and higher risk of ESKD progression.", "protein": "Lactate dehydrogenase A (LDHA)", "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "low", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Altered glycosylation of platelet glycoproteins may increase their pro-fibrotic activity.", "mechanism": "Platelet activation promotes inflammation and fibrosis, exacerbating DKD.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10913800" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects albumin's filtration properties.", "mechanism": "Microalbuminuria is an early indicator of renal involvement in T2DM.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913800" }, { "confidence": "high", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "Opioid binding leads to CNS depression and respiratory depression.", "protein": "Opioid receptors (mu, delta, kappa)", "relationship_type": "causal", "source_pmcid": "PMC10913887" }, { "confidence": "medium", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "N-glycosylation affects NMDA receptor function and localization.", "mechanism": "Gabapentinoids antagonize NMDA receptor, potentiating opioid CNS depression.", "protein": "NMDA receptor", "protein_enriched": { "function": "Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed", "gene_name": "Grin1", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G80920RR", "G83555HU", "G31852PQ", "G41247ZX", "G62765YT", "G02815KT", "G09775CH", "G14548ZL", "G37135JQ", "G55220VL", "G60230HH", "G80966KZ", "G49108TO" ], "uniprot_id": "P35439" }, "relationship_type": "causal", "source_pmcid": "PMC10913887" }, { "confidence": "medium", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation regulates transporter surface expression.", "mechanism": "Opioids slow gastric motility, increasing gabapentinoid absorption via transporters.", "protein": "Gabapentin transporter (LAT1/SLC7A5)", "relationship_type": "causal", "source_pmcid": "PMC10913887" }, { "confidence": "high", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Not specified; formulation-dependent.", "mechanism": "Naloxone reverses opioid receptor activation, treating overdose.", "protein": "Naloxone", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10913887" }, { "confidence": "medium", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Concomitant serotonergic agent use increases ORO risk with gabapentinoids.", "protein": "Serotonin transporter (SERT/SLC6A4)", "relationship_type": "biomarker", "source_pmcid": "PMC10913887" }, { "confidence": "medium", "disease": "Sedation", "glycan_involvement": "Glycosylation influences receptor assembly and function.", "mechanism": "Gabapentinoids modulate GABAergic transmission, increasing sedation.", "protein": "GABA receptor", "relationship_type": "causal", "source_pmcid": "PMC10913887" }, { "confidence": "low", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation affects albumin stability and drug binding.", "mechanism": "Albumin levels recorded as part of liver function assessment in ORO risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913887" }, { "confidence": "low", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation modulates channel function.", "mechanism": "Concomitant anticonvulsant use associated with increased gabapentinoid exposure and ORO risk.", "protein": "Anticonvulsant targets (e.g., voltage-gated calcium channels)", "relationship_type": "biomarker", "source_pmcid": "PMC10913887" }, { "confidence": "low", "disease": "Opioid-related overdose (ORO)", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "Concomitant antipsychotic use associated with ORO risk.", "protein": "Antipsychotic targets (e.g., dopamine receptor D2)", "protein_enriched": { "function": "Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEG", "gene_name": "DRD2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P14416" }, "relationship_type": "biomarker", "source_pmcid": "PMC10913887" }, { "confidence": "high", "disease": "Respiratory depression", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "Opioid activation suppresses respiratory centers.", "protein": "Opioid receptors (mu, delta, kappa)", "relationship_type": "causal", "source_pmcid": "PMC10913887" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation defect (galactose-deficiency) in IgA1 hinge region increases antigenicity and pathogenicity.", "mechanism": "Gd-IgA1 forms immune complexes that deposit in the glomerular mesangium, triggering inflammation and injury.", "protein": "Galactose-deficient IgA1 (Gd-IgA1)", "relationship_type": "causal", "source_pmcid": "PMC10914012" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation status determines pathogenicity; galactose-deficient forms are most pathogenic.", "mechanism": "Mesangial deposition of IgA1 is diagnostic for IgAN.", "protein": "Immunoglobulin A1 (IgA1)", "relationship_type": "biomarker", "source_pmcid": "PMC10914012" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Indirect; drives production of aberrantly glycosylated IgA1.", "mechanism": "BLyS promotes B cell maturation and survival, leading to increased Gd-IgA1 production.", "protein": "B-lymphocyte stimulator (BLyS/BAFF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914012" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Promotes production of Gd-IgA1 via B cell/plasma cell differentiation.", "mechanism": "APRIL stimulates plasma cell survival and abnormal IgA glycosylation.", "protein": "A proliferation-inducing ligand (APRIL)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Binds preferentially to aberrantly glycosylated IgA1.", "mechanism": "CD71 mediates mesangial endocytosis of IgA1 complexes, leading to cell injury.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "causal", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Recognizes mannose-rich glycans on immune complexes.", "mechanism": "MBL deposits in mesangium, activating lectin complement pathway and promoting inflammation.", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Activated by MBL binding to glycans on immune complexes.", "mechanism": "MASP-2 activates complement via lectin pathway; inhibition reduces proteinuria and preserves renal function.", "protein": "MASP-2", "protein_enriched": { "function": "Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their ac", "gene_name": "MASP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN" ], "uniprot_id": "O00187" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Activated downstream of glycan-recognizing lectin pathway.", "mechanism": "C3 deposition in mesangium correlates with disease activity and progression.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Lectin pathway activation depends on glycan recognition.", "mechanism": "C4d deposition indicates complement activation via lectin pathway.", "protein": "Complement C4d", "relationship_type": "biomarker", "source_pmcid": "PMC10914012" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Alternative pathway activation is downstream of glycan recognition.", "mechanism": "Properdin stabilizes alternative pathway C3 convertase; its deposition is linked to disease progression.", "protein": "Properdin", "protein_enriched": { "function": "A positive regulator of the alternate pathway (AP) of complement (PubMed:16301317, PubMed:20382442, PubMed:28264884, PubMed:9748277). It binds to and stabilizes the C3- and C5-convertase enzyme comple", "gene_name": "CFP", "glycan_count": 4, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G61491DK", "G36855WW", "G08293MJ", "G81315DD" ], "uniprot_id": "P27918" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914012" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect ApoE structure and interaction with amyloid-beta.", "mechanism": "ApoE \u03b54 allele increases risk for late-onset Alzheimer's disease; gene dose effect observed.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10914050" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate ApoE isoform function.", "mechanism": "ApoE \u03b52 allele confers protective effect against late-onset Alzheimer's disease.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective", "source_pmcid": "PMC10914050" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation status may influence lipid binding and clearance.", "mechanism": "ApoE deficiency leads to severe hypercholesterolemia and arterial lesions in mouse models.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC10914050" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "Glycosylation may affect ApoE's lipid transport function.", "mechanism": "ApoE-deficient mice develop spontaneous hypercholesterolemia.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC10914050" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation may regulate ApoE's immune interactions.", "mechanism": "ApoE modulates inflammatory pathways in adipocytes and macrophages.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "modulator", "source_pmcid": "PMC10914050" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation could impact therapeutic efficacy.", "mechanism": "ApoE is a target for emerging Alzheimer's disease therapies.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914050" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect ApoE isoform distribution.", "mechanism": "ApoE polymorphism is associated with atherosclerosis risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914050" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence ApoE detection in assays.", "mechanism": "ApoE genotype is used as a biomarker for Alzheimer's disease risk stratification.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914050" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect drug binding and efficacy.", "mechanism": "ApoE is considered a target for intervention in lipid disorders and atherosclerosis.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914050" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "Glycosylation may impact ApoE quantification.", "mechanism": "ApoE levels and isoforms are biomarkers for lipid metabolism disorders.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914050" }, { "confidence": "medium", "disease": "Acute severe hepatitis of unknown etiology (ASHUE)", "glycan_involvement": "Adenovirus capsid proteins are highly glycosylated, mediating host cell entry and immune evasion.", "mechanism": "Adenovirus infection (mainly serotype 41) is detected in majority of ASHUE cases, suggesting a direct or cofactor role in liver injury.", "protein": "Adenovirus capsid proteins", "relationship_type": "causal", "source_pmcid": "PMC10914120" }, { "confidence": "low", "disease": "Acute severe hepatitis of unknown etiology (ASHUE)", "glycan_involvement": "Spike protein is heavily glycosylated, influencing immune recognition and cell entry.", "mechanism": "SARS-CoV-2 detected in a minority of ASHUE cases; possible but unproven role in liver injury.", "protein": "SARS-CoV-2 spike protein", "relationship_type": "causal", "source_pmcid": "PMC10914120" }, { "confidence": "low", "disease": "Acute severe hepatitis of unknown etiology (ASHUE)", "glycan_involvement": "Altered glycosylation patterns in liver disease.", "mechanism": "Serum glycoproteins like transferrin may be altered in liver dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914120" }, { "confidence": "low", "disease": "Acute severe hepatitis of unknown etiology (ASHUE)", "glycan_involvement": "Ferritin is glycosylated; glycan changes may reflect disease state.", "mechanism": "Elevated ferritin observed in some ASHUE cases, reflecting inflammation or liver injury.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914120" }, { "confidence": "high", "disease": "Adenovirus infection", "glycan_involvement": "Glycosylation critical for host cell binding.", "mechanism": "Adenovirus capsid glycoproteins mediate infection and pathogenesis.", "protein": "Adenovirus capsid proteins", "relationship_type": "causal", "source_pmcid": "PMC10914120" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans shield epitopes from immune detection.", "mechanism": "Spike glycoprotein mediates viral entry and immune evasion.", "protein": "SARS-CoV-2 spike protein", "relationship_type": "causal", "source_pmcid": "PMC10914120" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may modulate immune response and tissue tropism.", "mechanism": "Severe adenovirus infection can progress to acute liver failure in children.", "protein": "Adenovirus capsid proteins", "relationship_type": "causal", "source_pmcid": "PMC10914120" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10914132" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects spike binding affinity.", "mechanism": "Host receptor for spike protein; blocking interaction prevents viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status influences spike-CD147 interaction.", "mechanism": "Alternative host receptor for spike protein; drugs targeting CD147 may block viral entry.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for proper folding and activity.", "mechanism": "Facilitates spike protein activation for viral entry; inhibitors block infection.", "protein": "Cathepsin L", "protein_enriched": { "function": "Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone r", "gene_name": "CTSL", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G06110VR", "G06356OH", "G14669DU", "G22310AV", "G28681TP", "G31665QC", "G31852PQ", "G37881RL", "G39188ZX", "G41247ZX", "G43089EG", "G47518TP", "G48414YA", "G49589RB", "G50282JC", "G52527GH", "G62765YT", "G71784JC", "G75983OB", "G80920RR", "G92050GC", "G92275SC", "G96091TT" ], "uniprot_id": "P07711" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and localization.", "mechanism": "Primes spike protein for fusion; inhibitors (camostat, nafamostat) block entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates receptor binding and antigenicity.", "mechanism": "Mediates viral entry via sialic acid receptors.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycan moieties serve as viral attachment factors.", "mechanism": "Spike protein binds gangliosides on host cell surface; chloroquine blocks this interaction.", "protein": "Gangliosides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Terminal sialic acids on glycoproteins/glycolipids mediate viral binding.", "mechanism": "Potential host attachment factors for spike protein; chloroquine may suppress biosynthesis.", "protein": "Sialic acid receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may regulate protein function and virion formation.", "mechanism": "Involved in virion assembly and budding; chloroquine may affect maturation.", "protein": "M protein", "protein_enriched": { "function": "Modulates RecA activity", "gene_name": "recX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DD93" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycopeptide structure enables interaction with glycoprotein targets.", "mechanism": "Blocks viral entry by inhibiting cathepsin L; also inhibits 3CLpro.", "protein": "Teicoplanin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914132" }, { "confidence": "high", "disease": "Herpes simplex virus type-1 (HSV-1) infection", "glycan_involvement": "gD is a glycoprotein; glycosylation is essential for proper folding and receptor interaction.", "mechanism": "gD binds TRPC1 at plasma membrane, facilitating viral entry via MCS-mediated calcium signaling.", "protein": "HSV-1 glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "high", "disease": "Influenza A infection", "glycan_involvement": "NPC1 is a glycoprotein; glycosylation affects trafficking and function.", "mechanism": "NPC1 mobilizes cholesterol to ER/plasma membrane, supporting viral assembly.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "Vesicular stomatitis virus infection", "glycan_involvement": "G protein is glycosylated; glycosylation required for membrane fusion and infectivity.", "mechanism": "Cholesterol loading (regulated by MCS proteins) prevents G protein trafficking to plasma membrane, inhibiting viral egress.", "protein": "Vesicular stomatitis virus protein G", "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "high", "disease": "Human cytomegalovirus (HCMV) infection", "glycan_involvement": "Envelope glycoproteins are heavily glycosylated, impacting immune evasion and infectivity.", "mechanism": "HCMV induces plasmalogen synthesis via ER\u2013peroxisome MCSs; plasmalogens are enriched in viral envelope.", "protein": "HCMV envelope glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "high", "disease": "Rhinovirus infection", "glycan_involvement": "OSBP1 is glycosylated; glycosylation may affect localization and function.", "mechanism": "OSBP1 mediates cholesterol/PI4P exchange at ER\u2013Golgi MCSs, essential for viral replication organelle formation.", "protein": "OSBP1", "protein_enriched": { "function": "Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), d", "gene_name": "OSBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P22059" }, "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "Human cytomegalovirus (HCMV) infection", "glycan_involvement": "VAPB is glycosylated; glycosylation may regulate MCS formation.", "mechanism": "VAPB localizes to MENCs and ER\u2013peroxisome MCSs, supporting lipid exchange and viral replication.", "protein": "VAPB", "protein_enriched": { "function": "Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMe", "gene_name": "VAPB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95292" }, "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "Human cytomegalovirus (HCMV) infection", "glycan_involvement": "ACBD5 is glycosylated; glycosylation may affect peroxisomal targeting.", "mechanism": "ACBD5 interacts with VAPB to promote ER\u2013peroxisome contacts, plasmalogen synthesis, and peroxisome enlargement.", "protein": "ACBD5", "protein_enriched": { "function": "Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters", "gene_name": "ACBD5", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "Q5T8D3" }, "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "Hemorrhagic fever virus infection", "glycan_involvement": "STIM1 is glycosylated; glycosylation may modulate calcium sensing.", "mechanism": "Viral matrix proteins trigger ER calcium release, STIM1 relocalizes to plasma membrane, promoting calcium influx for viral egress.", "protein": "STIM1", "protein_enriched": { "function": "Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC)", "gene_name": "STIM1", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G02815KT", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G46503DX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G80920RR" ], "uniprot_id": "Q13586" }, "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "Poliovirus infection", "glycan_involvement": "VDACs are glycoproteins; glycosylation may affect channel function.", "mechanism": "VDAC-mediated calcium influx into mitochondria triggers apoptosis, facilitating viral pathogenesis.", "protein": "VDACs", "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "VDACs are glycoproteins; glycosylation may affect channel function.", "mechanism": "VDAC-mediated calcium influx induces mitochondrial collapse and apoptosis during infection.", "protein": "VDACs", "relationship_type": "causal", "source_pmcid": "PMC10914265" }, { "confidence": "high", "disease": "Lung cancer (adenocarcinoma)", "glycan_involvement": "ABCG2 is a glycosylated transmembrane protein; glycosylation is essential for its membrane localization and function.", "mechanism": "ABCG2 efflux pump reduces protein aggregation and increases survival of A549 lung cancer cells exposed to cigarette smoke condensate.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "protective", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation required for ABCG2 stability and trafficking.", "mechanism": "Low ABCG2 expression in non-cancerous lung cells correlates with increased protein aggregation and cell death upon cigarette smoke exposure.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "protective", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "Emphysema", "glycan_involvement": "Glycosylation supports ABCG2 function.", "mechanism": "ABCG2 upregulation in cancer cells mitigates smoke-induced protein aggregation, a process implicated in emphysema pathology.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "protective", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "Lung cancer (adenocarcinoma)", "glycan_involvement": "Minor glycosylation may affect stability; not discussed in detail.", "mechanism": "Aggregation of P53 contributes to cancer progression.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "causal", "source_pmcid": "PMC10914296" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Cigarette smoke exposure leads to accumulation of ubiquitinated protein aggregates in lung tissue.", "protein": "Ubiquitinated proteins", "relationship_type": "causal", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; glycosylation may modulate aggregation propensity.", "mechanism": "Cigarette smoke increases tau phosphorylation and amyloidogenesis (protein aggregation) in Alzheimer's models.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation affects processing and aggregation.", "mechanism": "Cigarette smoke promotes amyloidogenesis, increasing protein aggregation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC10914296" }, { "confidence": "high", "disease": "Lung cancer (adenocarcinoma)", "glycan_involvement": "Glycosylation is necessary for ABCG2 function; targeting glycosylation may modulate activity.", "mechanism": "Inhibition or downregulation of ABCG2 increases protein aggregation and cell vulnerability to cigarette smoke.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914296" }, { "confidence": "medium", "disease": "Emphysema", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Protein aggregation due to impaired autophagy and increased ubiquitination is implicated in emphysema pathology.", "protein": "Ubiquitinated proteins", "relationship_type": "causal", "source_pmcid": "PMC10914296" }, { "confidence": "high", "disease": "Lung cancer (adenocarcinoma)", "glycan_involvement": "Glycosylation status may affect ABCG2 detection and function.", "mechanism": "High ABCG2 expression marks cancer cell adaptation to cigarette smoke toxicity.", "protein": "ABCG2 (Breast Cancer Resistance Protein)", "relationship_type": "biomarker", "source_pmcid": "PMC10914296" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycation of hemoglobin (not enzymatic glycosylation); reflects glucose exposure.", "mechanism": "HbA1c reflects average blood glucose levels and is used to diagnose and monitor T2DM.", "protein": "Glycosylated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC10914329" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated fatty liver disease (MAFLD)", "glycan_involvement": "Glycation of hemoglobin correlates with metabolic status.", "mechanism": "Elevated HbA1c is associated with metabolic dysregulation and increased risk of MAFLD.", "protein": "Glycosylated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC10914329" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Myostatin is a glycoprotein; glycosylation may affect secretion and activity.", "mechanism": "Myostatin negatively regulates skeletal muscle mass; increased myostatin promotes muscle loss.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC10914329" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated fatty liver disease (MAFLD)", "glycan_involvement": "Glycosylation may modulate myostatin's endocrine function.", "mechanism": "Myostatin secreted by muscle influences liver steatosis and metabolic regulation.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC10914329" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect myostatin's stability and signaling.", "mechanism": "Myostatin contributes to fat accumulation in the liver and progression of NAFLD.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC10914329" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Glycation status indicates metabolic stress affecting muscle.", "mechanism": "Elevated HbA1c may reflect insulin resistance, which is linked to muscle mass loss.", "protein": "Glycosylated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC10914329" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may regulate myostatin's activity in metabolic pathways.", "mechanism": "Myostatin-induced muscle loss contributes to insulin resistance and T2DM risk.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC10914329" }, { "confidence": "high", "disease": "Disseminated Aspergillosis", "glycan_involvement": "Galactomannan is a polysaccharide glycan component of fungal glycoproteins.", "mechanism": "Galactomannan is released from Aspergillus cell wall during infection and detected in serum for diagnosis.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC10914378" }, { "confidence": "high", "disease": "Disseminated Aspergillosis", "glycan_involvement": "Glycosylation is essential for fungal cell wall integrity and host invasion.", "mechanism": "Fungal glycoproteins mediate angioinvasion and tissue dissemination.", "protein": "Aspergillus glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "medium", "disease": "Acute Ischaemic Stroke (AIS)", "glycan_involvement": "Glycosylated fungal proteins interact with host endothelium.", "mechanism": "Angioinvasive Aspergillus glycoproteins facilitate vascular invasion, leading to embolic stroke.", "protein": "Aspergillus glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "medium", "disease": "Mediastinal Mass/Invasion", "glycan_involvement": "Glycosylation supports fungal adhesion and immune evasion.", "mechanism": "Fungal glycoproteins promote tissue invasion and granuloma formation.", "protein": "Aspergillus glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "medium", "disease": "Haemorrhagic Transformation", "glycan_involvement": "Glycosylation enables fungal penetration of vessel walls.", "mechanism": "Angioinvasion by fungal glycoproteins disrupts vascular integrity, predisposing to haemorrhage.", "protein": "Aspergillus glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "low", "disease": "Disseminated Aspergillosis", "glycan_involvement": "Host glycosylation patterns may influence susceptibility to fungal adhesion.", "mechanism": "Fungal glycoproteins interact with host endothelial glycoproteins to facilitate invasion.", "protein": "Host endothelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "medium", "disease": "Mediastinal Mass/Invasion", "glycan_involvement": "Galactomannan is a glycan released during fungal growth.", "mechanism": "Galactomannan detection supports diagnosis of mediastinal Aspergillus infection.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC10914378" }, { "confidence": "low", "disease": "Acute Ischaemic Stroke (AIS)", "glycan_involvement": "Reflects fungal glycoprotein activity in vasculature.", "mechanism": "Galactomannan may be elevated in serum during angioinvasive fungal stroke.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC10914378" }, { "confidence": "low", "disease": "Bronchiectasis", "glycan_involvement": "Fungal glycoproteins trigger immune responses.", "mechanism": "Chronic Aspergillus infection may contribute to bronchiectasis via glycoprotein-mediated inflammation.", "protein": "Aspergillus glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "low", "disease": "Haemorrhagic Transformation", "glycan_involvement": "Altered glycosylation may affect vascular stability.", "mechanism": "Disruption of host glycoproteins by fungal invasion leads to vessel rupture.", "protein": "Host endothelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10914378" }, { "confidence": "high", "disease": "MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody binding", "mechanism": "MOG antibodies trigger demyelination in CNS, including meninges and optic nerve", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC10914404" }, { "confidence": "medium", "disease": "Hypertrophic pachymeningitis (HP)", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition", "mechanism": "MOG antibodies implicated in immune-mediated HP via CNS demyelination and inflammation", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC10914404" }, { "confidence": "high", "disease": "Hypertrophic pachymeningitis (HP)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects stability and function", "mechanism": "Elevated CRP reflects systemic inflammation in HP", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "high", "disease": "IgG4-related disease", "glycan_involvement": "IgG4 glycosylation modulates effector function and immune complex formation", "mechanism": "IgG4-positive plasma cell infiltration causes systemic inflammation, including HP", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC10914404" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "IgM glycosylation influences immune complex formation", "mechanism": "RF is an autoantibody present in RA and associated with HP", "protein": "Rheumatoid factor (RF, IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "high", "disease": "Granulomatosis with polyangiitis (GPA)", "glycan_involvement": "PR3 is glycosylated; glycan structures may affect antigenicity", "mechanism": "PR3-ANCA autoantibodies are diagnostic for GPA, which can cause HP", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "high", "disease": "ANCA-associated vasculitis", "glycan_involvement": "MPO glycosylation may influence immune recognition", "mechanism": "MPO-ANCA autoantibodies are diagnostic for vasculitis, which can cause HP", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "medium", "disease": "Hypertrophic pachymeningitis (HP)", "glycan_involvement": "IgG4 glycosylation modulates immune effector functions", "mechanism": "IgG4-related disease can manifest as HP via immune-mediated fibrosis", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC10914404" }, { "confidence": "medium", "disease": "Granulomatosis with polyangiitis (GPA)", "glycan_involvement": "CRP glycosylation affects its inflammatory activity", "mechanism": "Elevated CRP indicates active inflammation in GPA", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "medium", "disease": "Hypertrophic pachymeningitis (HP)", "glycan_involvement": "PR3 glycosylation may affect autoantibody binding", "mechanism": "PR3-ANCA positivity is associated with HP secondary to GPA", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914404" }, { "confidence": "high", "disease": "Autosomal Dominant Polycystic Kidney Disease (ADPKD)", "glycan_involvement": "PC-1 is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Mutations in PKD-1 gene reduce PC-1 levels, leading to cyst formation in kidneys and liver.", "protein": "Polycystin-1 (PC-1)", "protein_enriched": { "function": "Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both ", "gene_name": "PKD1", "glycan_count": 8, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G80920RR", "G62765YT", "G31852PQ", "G90575OW", "G97829MZ", "G43769HG", "G26436YP", "G49108TO" ], "uniprot_id": "P98161" }, "relationship_type": "causal", "source_pmcid": "PMC10914406" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation of PC-1 affects its interaction with E-cadherin and cell-matrix adhesion.", "mechanism": "Defective PC-1 impairs cell adhesion and polarity, promoting uncontrolled cell proliferation and carcinogenesis.", "protein": "Polycystin-1 (PC-1)", "protein_enriched": { "function": "Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both ", "gene_name": "PKD1", "glycan_count": 8, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G80920RR", "G62765YT", "G31852PQ", "G90575OW", "G97829MZ", "G43769HG", "G26436YP", "G49108TO" ], "uniprot_id": "P98161" }, "relationship_type": "causal", "source_pmcid": "PMC10914406" }, { "confidence": "high", "disease": "Polycystic Liver Disease", "glycan_involvement": "Glycosylation required for PC-1 function in hepatic tissue.", "mechanism": "Reduced PC-1 due to PKD-1 mutations leads to cyst formation in the liver.", "protein": "Polycystin-1 (PC-1)", "protein_enriched": { "function": "Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both ", "gene_name": "PKD1", "glycan_count": 8, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G80920RR", "G62765YT", "G31852PQ", "G90575OW", "G97829MZ", "G43769HG", "G26436YP", "G49108TO" ], "uniprot_id": "P98161" }, "relationship_type": "causal", "source_pmcid": "PMC10914406" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "CEA is a heavily glycosylated protein; glycan structures influence its detection and function.", "mechanism": "Elevated CEA levels indicate presence and progression of gastric adenocarcinoma.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC10914406" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation modulates E-cadherin-mediated cell adhesion.", "mechanism": "PC-1 interacts with E-cadherin; loss of function disrupts cell adhesion, facilitating tumor invasion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC10914406" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation status may affect PC-1's regulatory role in mTOR signaling.", "mechanism": "PC-1 dysfunction upregulates mTOR signaling, a targetable pathway in gastric cancer.", "protein": "Polycystin-1 (PC-1)", "protein_enriched": { "function": "Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both ", "gene_name": "PKD1", "glycan_count": 8, "glycosylation_sites_count": 60, "glytoucan_ids": [ "G80920RR", "G62765YT", "G31852PQ", "G90575OW", "G97829MZ", "G43769HG", "G26436YP", "G49108TO" ], "uniprot_id": "P98161" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914406" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LOX-1 is a C-type lectin glycoprotein; glycosylation is essential for ligand binding and cell surface expression.", "mechanism": "LOX-1 mediates oxLDL uptake, foam cell formation, endothelial dysfunction, and vascular inflammation.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "TLR4 is glycosylated; glycosylation affects receptor folding, trafficking, and ligand recognition.", "mechanism": "TLR4 activation induces inflammatory cytokines, promotes foam cell formation, and contributes to plaque progression and rupture.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "PCSK9 is glycosylated; glycosylation affects secretion and function.", "mechanism": "PCSK9 promotes LDLR degradation, increases LDL cholesterol, and enhances vascular inflammation and SMC proliferation.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Plaque rupture", "glycan_involvement": "Glycosylation required for LOX-1 function in ligand binding and signaling.", "mechanism": "LOX-1/oxLDL interaction induces MMPs and apoptosis, destabilizing plaques.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Plaque rupture", "glycan_involvement": "Glycosylation modulates TLR4 signaling and cell surface expression.", "mechanism": "TLR4 activation in macrophages induces MMP9 and proteolytic enzymes, leading to fibrous cap degradation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation affects PCSK9 stability and activity.", "mechanism": "Elevated PCSK9 correlates with increased risk and inflammation; inhibition reduces events.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation critical for LOX-1 ligand binding and signaling.", "mechanism": "LOX-1/oxLDL axis impairs NO production, increases ROS, and induces EC apoptosis.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "PCSK9 glycosylation required for secretion and LDLR interaction.", "mechanism": "PCSK9 degrades LDLR, raising LDL cholesterol; inhibition lowers cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10914434" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "Glycosylation influences PCSK9 secretion and activity.", "mechanism": "PCSK9 affects ovarian lipid metabolism and endocrine dysfunction; inhibition improves phenotype.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC10914434" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "HMGB1 is glycosylated; glycosylation may affect extracellular signaling.", "mechanism": "HMGB1 interacts with TLR4 and LOX-1, promoting inflammation and plaque progression.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC10914434" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "AAT is a glycoprotein; glycosylation is required for stability and secretion.", "mechanism": "Loss of AAT antiprotease function leads to unchecked neutrophil elastase activity.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Liver disease (AATD-related)", "glycan_involvement": "Misfolding may alter glycosylation, affecting secretion and aggregation.", "mechanism": "Misfolded Z-AAT aggregates in hepatocytes, causing toxicity and liver damage.", "protein": "Mutant Z-AAT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "Altered glycosylation may contribute to ER retention and aggregation.", "mechanism": "Z-AAT polymerization reduces circulating AAT, causing deficiency.", "protein": "Mutant Z-AAT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Chronic lung disease", "glycan_involvement": "Glycosylation is essential for M-AAT stability and function.", "mechanism": "M-AAT inhibits neutrophil elastase, protecting lung tissue.", "protein": "Wild-type M-AAT", "relationship_type": "protective", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Chronic lung disease", "glycan_involvement": "Defective glycosylation may impair secretion.", "mechanism": "Low circulating Z-AAT fails to inhibit elastase, leading to lung damage.", "protein": "Mutant Z-AAT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Chronic lung disease", "glycan_involvement": "Glycosylation status affects detection and quantification.", "mechanism": "Serum AAT levels are used to diagnose and monitor lung disease risk.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Liver disease (AATD-related)", "glycan_involvement": "Targeting misfolded glycoprotein may depend on glycan-mediated ER retention.", "mechanism": "Silencing Z-AAT expression can reduce hepatocyte toxicity.", "protein": "Mutant Z-AAT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "Therapeutic M-AAT must be properly glycosylated for efficacy.", "mechanism": "Gene therapy to augment M-AAT can restore antiprotease activity.", "protein": "Wild-type M-AAT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914479" }, { "confidence": "medium", "disease": "Liver disease (AATD-related)", "glycan_involvement": "Glycosylation status may influence aggregation propensity.", "mechanism": "AAT aggregation in liver is a marker of disease severity.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC10914479" }, { "confidence": "medium", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "Glycan modifications may affect polymer detection.", "mechanism": "Presence of Z-AAT polymers in liver biopsies indicates disease.", "protein": "Mutant Z-AAT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10914479" }, { "confidence": "high", "disease": "CCl4-induced hepatic injury", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated ALP indicates hepatocyte membrane damage and leakage.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "high", "disease": "CCl4-induced hepatic injury", "glycan_involvement": "ALT is glycosylated; glycosylation modulates its serum half-life.", "mechanism": "ALT elevation reflects hepatocellular injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "CCl4-induced hepatic injury", "glycan_involvement": "OATP1B1 glycosylation is critical for membrane localization and function.", "mechanism": "Impaired transporter function leads to increased serum bilirubin.", "protein": "Bilirubin transporter (OATP1B1)", "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "GGT glycosylation affects its enzymatic activity and stability.", "mechanism": "Elevated GGT is indicative of cholestatic or hepatocellular injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "CCl4-induced hepatic injury", "glycan_involvement": "AST glycosylation influences its release and activity.", "mechanism": "AST elevation signals hepatocyte damage.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Acute hepatitis", "glycan_involvement": "Glycosylation modulates ALP's serum levels.", "mechanism": "ALP is elevated in acute hepatitis due to bile duct injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation affects ALT's stability and detection.", "mechanism": "ALT is a sensitive marker for acute liver failure.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Hepatic cirrhosis", "glycan_involvement": "Altered glycosylation may affect ALP activity in cirrhosis.", "mechanism": "ALP is elevated in cirrhosis due to cholestasis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation impacts ALT's secretion and function.", "mechanism": "ALT is increased in steatosis due to hepatocyte injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "medium", "disease": "Drug-induced hepatotoxicity", "glycan_involvement": "Glycosylation state may change in response to injury.", "mechanism": "ALP elevation is a marker of drug-induced liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC10914973" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "NUP98 is an FG-repeat glycoprotein; its glycosylation status not directly discussed but FG repeats are O-glycosylated.", "mechanism": "NUP98 impedes HIV-1 LTR-driven basal gene expression, reducing viral RNA, protein, and infectivity.", "protein": "NUP98", "relationship_type": "protective", "source_pmcid": "PMC10914986" }, { "confidence": "medium", "disease": "AIDS", "glycan_involvement": "FG-repeat region may be O-glycosylated, potentially influencing interactions.", "mechanism": "By restricting HIV-1 propagation, NUP98 may delay progression to AIDS.", "protein": "NUP98", "relationship_type": "protective", "source_pmcid": "PMC10914986" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "No direct evidence for glycan modification change, but NUP98 is a glycoprotein.", "mechanism": "HIV-1 infection downregulates NUP98 protein post-transcriptionally, possibly to evade its restriction.", "protein": "NUP98", "relationship_type": "causal", "source_pmcid": "PMC10914986" }, { "confidence": "low", "disease": "HIV-1 infection", "glycan_involvement": "FG-repeat glycoprotein; glycosylation not discussed.", "mechanism": "NUP62 involved in HIV-1 RNA export; not significantly altered by infection in this study.", "protein": "NUP62", "relationship_type": "causal", "source_pmcid": "PMC10914986" }, { "confidence": "low", "disease": "HIV-1 infection", "glycan_involvement": "FG-repeat glycoprotein; glycosylation not discussed.", "mechanism": "NUP153 supports HIV-1 nuclear import and integration; not altered by infection in this study.", "protein": "NUP153", "protein_enriched": { "function": "Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:262915", "gene_name": "SDCBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00560" }, "relationship_type": "causal", "source_pmcid": "PMC10914986" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycan involvement.", "mechanism": "MX2 restricts HIV-1 by interacting with NUP98 and other NUPs, blocking nuclear import.", "protein": "MX2", "protein_enriched": { "function": "Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1). Acts by targeting the viral capsid and affects the nuclear uptake and/or stab", "gene_name": "MX2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20592" }, "relationship_type": "protective", "source_pmcid": "PMC10914986" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycan involvement.", "mechanism": "APOBEC3G is packaged into virions and induces lethal mutations in HIV-1 genome.", "protein": "APOBEC3G", "protein_enriched": { "function": "DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:12808465, PubMed:165277", "gene_name": "APOBEC3G", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC16" }, "relationship_type": "protective", "source_pmcid": "PMC10914986" }, { "confidence": "low", "disease": "acute leukemia", "glycan_involvement": "Not discussed.", "mechanism": "NUP98 fusion proteins (e.g., NUP98-HOXA9) interact with HDAC1, altering gene expression in leukemia.", "protein": "NUP98", "relationship_type": "causal", "source_pmcid": "PMC10914986" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Extensive N-glycosylation critical for function and immune evasion.", "mechanism": "gp120 mediates viral entry; highly glycosylated, shields virus from immune detection.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC10914986" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Potential for glycan modification to modulate function, but not directly tested.", "mechanism": "Enhancing NUP98 function could suppress HIV-1 gene expression and propagation.", "protein": "NUP98", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10914986" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and secretion.", "mechanism": "IL-6 promotes inflammatory processes driving plaque formation and progression.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation modulates IL-6 bioactivity.", "mechanism": "Elevated IL-6 levels predict increased risk of MI and cardiovascular death.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "CRP is heavily glycosylated, influencing its solubility and function.", "mechanism": "hsCRP levels reflect downstream inflammation and predict residual cardiovascular risk.", "protein": "C-reactive protein (CRP/hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC10915057" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and receptor binding.", "mechanism": "IL-1\u03b2 drives vascular inflammation and plaque destabilization.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "causal", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL contains glycoprotein ApoB; glycosylation affects receptor binding and clearance.", "mechanism": "LDL accumulation in arterial walls initiates and propagates plaque formation.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915057" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "LDE surface mimics LDL glycoprotein structure for receptor targeting.", "mechanism": "LDE nanoparticles mimic LDL, target atherosclerotic lesions via LDL receptor-mediated uptake, delivering paclitaxel to reduce inflammation.", "protein": "Paclitaxel-LDE nanoparticle", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915057" }, { "confidence": "medium", "disease": "Thrombotic complications", "glycan_involvement": "Glycosylation modulates IL-6 receptor interactions.", "mechanism": "IL-6 promotes pro-thrombotic state in advanced atherosclerosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "CRP glycosylation is essential for its function in inflammation.", "mechanism": "Elevated hsCRP is associated with increased risk of MI.", "protein": "C-reactive protein (CRP/hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "ApoB glycosylation affects LDL metabolism.", "mechanism": "High LDL levels are a major risk factor for CAD.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915057" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation impacts IL-1\u03b2 stability and activity.", "mechanism": "IL-1\u03b2 levels reflect ongoing vascular inflammation.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915057" }, { "confidence": "high", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "Albumin glycosylation affects drug binding and distribution.", "mechanism": "Low serum albumin increases free linezolid, raising thrombocytopenia risk.", "protein": "Serum Albumin", "relationship_type": "protective", "source_pmcid": "PMC10915059" }, { "confidence": "high", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "Platelet surface glycoproteins mediate immune and drug interactions.", "mechanism": "Low baseline platelet glycoprotein levels predict higher risk.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Transferrin glycosylation modulates iron transport.", "mechanism": "Altered transferrin levels may indicate anemia risk during linezolid therapy.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "low", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "DBIL conjugation involves glycoprotein carriers.", "mechanism": "High DBIL is associated with increased risk.", "protein": "Direct Bilirubin (DBIL)", "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "medium", "disease": "Renal Insufficiency", "glycan_involvement": "Glycosylation regulates transporter function.", "mechanism": "Elevated urea indicates renal dysfunction, increasing thrombocytopenia risk.", "protein": "Urea Transporters", "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "medium", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "Glycoproteins involved in renal filtration.", "mechanism": "Low Ccr predicts higher risk.", "protein": "Creatinine Clearance (Ccr) Related Proteins", "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "low", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "ALT glycosylation affects enzyme activity.", "mechanism": "Elevated ALT may signal increased risk.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10915059" }, { "confidence": "medium", "disease": "Linezolid-induced Thrombocytopenia", "glycan_involvement": "Therapeutic albumin glycosylation may enhance drug binding.", "mechanism": "Albumin therapy reduces thrombocytopenia incidence.", "protein": "Human Serum Albumin (Therapeutic)", "relationship_type": "protective", "source_pmcid": "PMC10915059" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "Elevated CRP levels are associated with accelerated renal function decline in CKD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915063" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and activity.", "mechanism": "Higher IL-6 levels correlate with increased risk and progression of CKD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915063" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "TNF-\u03b1R2 is glycosylated, affecting ligand binding and signaling.", "mechanism": "TNF-\u03b1R2 levels increase with CKD stage; involved in inflammatory signaling.", "protein": "Tumor necrosis factor receptor 2 (TNF-\u03b1R2)", "relationship_type": "biomarker", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Albumin glycosylation influences renal filtration and clearance.", "mechanism": "Low serum albumin/globulin ratio is an independent indicator of CKD progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Leptin glycosylation affects receptor interaction and stability.", "mechanism": "Elevated leptin is negatively correlated with eGFR in CKD.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Siglec-F is a sialic acid-binding glycoprotein; glycosylation mediates cell-cell interactions.", "mechanism": "Siglec-F+ neutrophils promote a pro-fibrotic microenvironment and exacerbate renal fibrosis.", "protein": "Siglec-F", "protein_enriched": { "function": "", "gene_name": "Abo", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P38649" }, "relationship_type": "causal", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "TPO glycosylation affects receptor binding and activity.", "mechanism": "Renal-derived TPO increases myeloid cells and platelets, aggravating thromboinflammation in CKD.", "protein": "Thrombopoietin (TPO)", "protein_enriched": { "function": "Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major ", "gene_name": "THPO", "glycan_count": 32, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00227RN", "G00800WJ", "G01817YC", "G14389GM", "G16265MV", "G17689DH", "G44444MB", "G47058MH", "G56501FP", "G57789QC", "G90352XZ", "G94531EZ", "G00031MO", "G01614ZM", "G11629QQ", "G15169WU", "G19075PM", "G22310AV", "G29931IJ", "G39595FH", "G57321FI", "G57581QG", "G64394MX", "G65562ZE", "G69834CE", "G72667IM", "G74722FL", "G81006GJ", "G81263BG", "G84452RH", "G87015RU", "G96170OK" ], "uniprot_id": "P40225" }, "relationship_type": "causal", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "IL-1\u03b2 glycosylation modulates secretion and activity.", "mechanism": "IL-1\u03b2 maturation promotes inflammation and fibrosis in CKD.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "IL-18 glycosylation affects secretion and receptor binding.", "mechanism": "IL-18 axis influences sepsis, fibrosis, and vascular calcification in CKD.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915063" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation of CD8 modulates T cell activation and migration.", "mechanism": "IFN-\u03b3-producing CD8+ T cells prevent Th2 differentiation, reducing renal inflammation and fibrosis.", "protein": "CD8+ T cell surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC10915063" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "O-GlcNAcylation increases Foxp3 stability and immunosuppressive function.", "mechanism": "Foxp3 regulates Treg immunosuppressive function; its glycosylation enhances stability and suppressive activity, promoting tumor immune escape.", "protein": "Foxp3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915070" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation supports Foxp3 stability, preventing autoimmune toxicity.", "mechanism": "Foxp3 expression in Tregs maintains immune tolerance; loss or dysfunction leads to autoimmunity.", "protein": "Foxp3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC10915070" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation required for receptor function and antibody recognition.", "mechanism": "High CD25 expression on Tregs enables targeting by antibodies (e.g., daclizumab) to reduce Treg-mediated immunosuppression.", "protein": "CD25 (IL-2R alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation modulates receptor clustering and signaling.", "mechanism": "CD28 costimulation promotes Treg reprogramming via PI3K-Akt-mTOR pathway, enhancing immunosuppressive phenotype.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "causal", "source_pmcid": "PMC10915070" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation affects surface expression and antibody binding.", "mechanism": "CTLA-4 is highly expressed on Tregs; blockade with antibodies disrupts immunosuppression and enhances anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation required for chemokine binding and receptor function.", "mechanism": "CCR8 is selectively expressed on tumor-infiltrating Tregs and correlates with poor prognosis.", "protein": "CCR8", "protein_enriched": { "function": "Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection", "gene_name": "CCR8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51685" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation required for ligand binding and membrane localization.", "mechanism": "CD36 promotes fatty acid uptake and oxidation in Tregs, enhancing their immunosuppressive function in TME.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Glycosylation essential for transporter activity.", "mechanism": "Glut1 upregulation in Tregs increases glycolysis, supporting their survival and function in TME.", "protein": "Glut1 (SLC2A1)", "relationship_type": "causal", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Methylation and possible glycosylation modulate activity.", "mechanism": "SREBP1 regulates cholesterol biosynthesis and mevalonate pathway, supporting Treg reprogramming and immunosuppression.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "causal", "source_pmcid": "PMC10915070" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "O-GlcNAcylation directly modulates transcription factor activity.", "mechanism": "O-GlcNAcylation of c-Rel reduces its interaction with Foxp3, inhibiting Foxp3 expression and Treg function.", "protein": "c-Rel", "protein_enriched": { "function": "Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological ", "gene_name": "REL", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04864" }, "relationship_type": "causal", "source_pmcid": "PMC10915070" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding ACE2 on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915212" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects S protein binding affinity.", "mechanism": "Acts as the cellular receptor for SARS-CoV-2 S protein, facilitating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915212" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation influences receptor interaction and immune recognition.", "mechanism": "S protein binds ACE2, mediating entry of SARS-CoV.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915212" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor binding and immune escape.", "mechanism": "S protein mediates entry via DPP4 receptor (not ACE2).", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915212" }, { "confidence": "medium", "disease": "Long Covid", "glycan_involvement": "Glycosylation may affect immune persistence.", "mechanism": "Persistent S protein or immune response may contribute to post-viral symptoms.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10915212" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects membrane curvature and immune modulation.", "mechanism": "M protein is essential for viral assembly and suppresses interferon response.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC10915212" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status influences ion channel activity.", "mechanism": "E protein functions as ion channel, contributing to pathogenicity and acute respiratory stress.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915212" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation shields epitopes from immune recognition.", "mechanism": "gp41 mediates viral fusion; targeted by entry/fusion inhibitors.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915212" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and receptor binding.", "mechanism": "Haemagglutinin mediates viral entry; targeted by fusion inhibitors.", "protein": "Influenza haemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915212" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but interacts with glycoprotein maturation.", "mechanism": "PLpro is essential for viral polyprotein processing; targeted by natural inhibitors.", "protein": "SARS-CoV-2 PLpro", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915212" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "N-glycosylation affects stability and clearance", "mechanism": "Included in NIS4 panel for non-invasive diagnosis of high-risk NASH", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "N-glycosylation modulates secretion and function", "mechanism": "Part of NIS4 panel; elevated in NASH and fibrosis", "protein": "YKL-40 (Chitinase-3-like protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "high", "disease": "Advanced liver fibrosis", "glycan_involvement": "N-glycosylation required for complement activity", "mechanism": "Serum levels correlate with liver stiffness and fibrosis stage (F2-F4)", "protein": "Complement component C7", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "N-glycosylation influences complement assembly", "mechanism": "Elevated in patients with significant/advanced fibrosis", "protein": "Complement component C8 gamma chain", "protein_enriched": { "function": "Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane ", "gene_name": "C8G", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07360" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "N-glycosylation affects extracellular matrix interactions", "mechanism": "Serum levels associated with liver stiffness and fibrosis", "protein": "Fibulin-1", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "N-glycosylation modulates inhibitory activity", "mechanism": "Elevated in advanced fibrosis; involved in inflammation", "protein": "Alpha-1-antichymotrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for pentraxin structure", "mechanism": "Part of four-protein panel for fibrosis prediction", "protein": "Serum amyloid P component (SAP)", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects clotting and inflammation", "mechanism": "Included in four-protein panel for fibrosis assessment", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation modulates protein stability", "mechanism": "Part of four-protein panel for fibrosis prediction", "protein": "Olfactomedin", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects hormone binding", "mechanism": "Included in four-protein panel for fibrosis prediction", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC10915413" }, { "confidence": "high", "disease": "Anti-NMDAR encephalitis", "glycan_involvement": "Glycosylation affects NMDAR surface expression and antibody accessibility.", "mechanism": "Autoantibodies target NMDAR, leading to neurological and psychiatric symptoms.", "protein": "N-methyl D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "high", "disease": "Anti-IgLON5 encephalitis", "glycan_involvement": "IgLON5 is a glycosylated cell adhesion molecule; glycosylation may affect antibody binding.", "mechanism": "Autoantibodies against IgLON5 cause neurodegeneration and sleep disorder.", "protein": "IgLON family member 5 (IgLON5)", "protein_enriched": { "function": "Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) a", "gene_name": "PLD6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N2A8" }, "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "high", "disease": "Autoimmune encephalitis (AE)", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Presence of anti-NMDAR antibodies is diagnostic for AE subtype.", "protein": "N-methyl D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10915512" }, { "confidence": "medium", "disease": "Sleep disorder", "glycan_involvement": "Glycosylation may influence IgLON5 function in neuronal circuits.", "mechanism": "Anti-IgLON5 antibodies disrupt sleep architecture.", "protein": "IgLON family member 5 (IgLON5)", "protein_enriched": { "function": "Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) a", "gene_name": "PLD6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N2A8" }, "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "high", "disease": "Autoimmune encephalitis (AE)", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "Serum anti-IgLON5 antibodies indicate AE subtype.", "protein": "IgLON family member 5 (IgLON5)", "protein_enriched": { "function": "Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) a", "gene_name": "PLD6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N2A8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915512" }, { "confidence": "medium", "disease": "Anti-LGI1 encephalitis", "glycan_involvement": "LGI1 is glycosylated; glycosylation may affect immune recognition.", "mechanism": "Autoantibodies against LGI1 cause limbic encephalitis.", "protein": "Leucine-rich glioma inactivated 1 (LGI1)", "protein_enriched": { "function": "Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors (PubMed:14966521, PubMed", "gene_name": "LINGO1", "glycan_count": 3, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G92551JA", "G58665JE", "G83460ZZ" ], "uniprot_id": "Q96FE5" }, "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "medium", "disease": "Anti-MOG encephalitis", "glycan_involvement": "MOG glycosylation is critical for antigenicity.", "mechanism": "Anti-MOG antibodies cause demyelinating disease.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "medium", "disease": "Anti-GABA B encephalitis", "glycan_involvement": "Glycosylation may affect receptor conformation and antibody binding.", "mechanism": "Autoantibodies against GABA B R cause encephalitis.", "protein": "Gamma-aminobutyric acid B receptor (GABA B R)", "relationship_type": "causal", "source_pmcid": "PMC10915512" }, { "confidence": "high", "disease": "Malignant tumor", "glycan_involvement": "CEA is heavily glycosylated; glycan structures are important for detection.", "mechanism": "Elevated CEA is a marker for malignancy risk.", "protein": "Carcino-embryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC10915512" }, { "confidence": "low", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation status may influence immune surveillance.", "mechanism": "AE patients with anti-IgLON5 antibodies may have increased tumor risk.", "protein": "IgLON family member 5 (IgLON5)", "protein_enriched": { "function": "Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) a", "gene_name": "PLD6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N2A8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915512" }, { "confidence": "high", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Glycosylation affects ligand binding and platelet function.", "mechanism": "Mediates platelet adhesion to injured endothelium and thrombus; targeted by PITD for cell/drug delivery.", "protein": "GPIIb/IIIa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates receptor function and platelet adhesion.", "mechanism": "Facilitates platelet binding to vWF at sites of vascular injury; used in PITD for targeted delivery.", "protein": "GPIb-V-IX complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "Myocardial infarction (MI)", "glycan_involvement": "Glycosylation regulates receptor stability and function.", "mechanism": "Platelet collagen receptor involved in targeting platelets to injured myocardium.", "protein": "GPVI", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "high", "disease": "In-stent restenosis (ISR)", "glycan_involvement": "Glycosylation required for ligand binding (PSGL-1).", "mechanism": "Upregulated on activated endothelium post-stenting; mediates platelet adhesion and PITD targeting.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "Myocardial infarction (MI)", "glycan_involvement": "Glycosylation influences cell-cell interactions.", "mechanism": "Marker for endothelial progenitor cells; targeted by PITD to enhance cardiac repair.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation critical for multimerization and function.", "mechanism": "Binds platelet GPIb\u03b1 to mediate adhesion at injury sites; PITD exploits this for targeting.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "In-stent restenosis (ISR)", "glycan_involvement": "Glycosylation essential for ligand recognition.", "mechanism": "Expressed on activated endothelium; mediates platelet and leukocyte adhesion.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates adhesion properties.", "mechanism": "Upregulated in atherosclerotic lesions; mediates leukocyte adhesion.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "O-glycosylation required for binding to selectins.", "mechanism": "Ligand for P-selectin; mediates platelet-leukocyte interactions in thrombus formation.", "protein": "P-selectin glycoprotein ligand-1 (PSGL-1)", "protein_enriched": { "function": "Plays a role in odontogenesis", "gene_name": "SSUH2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2M2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "medium", "disease": "Myocardial infarction (MI)", "glycan_involvement": "Glycosylation affects integrin activation.", "mechanism": "Targeted by PITD for platelet hitchhiking to deliver progenitor cells to infarcted myocardium.", "protein": "CD41 (ITGA2B)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915553" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "APLP2 is a glycoprotein; glycosylation may affect its stability and function in cancer cells.", "mechanism": "APLP2 is abnormally upregulated and promotes tumor progression.", "protein": "APLP2", "protein_enriched": { "function": "May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the D", "gene_name": "APLP2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G00912UN", "G02815KT", "G07755XJ", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G31852PQ", "G34989PA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G62765YT", "G64409MC", "G75983OB", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW" ], "uniprot_id": "Q06481" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "No direct glycan involvement; acts upstream of glycoprotein APLP2.", "mechanism": "HMGA2 overexpression correlates with poor prognosis and promotes proliferation/invasion.", "protein": "HMGA2", "protein_enriched": { "function": "Functions as a transcriptional regulator. Functions in cell cycle regulation through CCNA2. Plays an important role in chromosome condensation during the meiotic G2/M transition of spermatocytes. Play", "gene_name": "HMGA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52926" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10915557" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "No direct glycan involvement; regulates glycoprotein APLP2 at RNA level.", "mechanism": "IGF2BP2 stabilizes APLP2 mRNA via m6A modification, promoting cancer progression.", "protein": "IGF2BP2", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6M1" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "APLP2 glycosylation may affect its processing and aggregation.", "mechanism": "APLP2 and homologs play a crucial role in disease development and progression.", "protein": "APLP2", "protein_enriched": { "function": "May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the D", "gene_name": "APLP2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G00912UN", "G02815KT", "G07755XJ", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G31852PQ", "G34989PA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G62765YT", "G64409MC", "G75983OB", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW" ], "uniprot_id": "Q06481" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of APP affects its cleavage and aggregation.", "mechanism": "APP is involved in amyloid plaque formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "No direct glycan involvement.", "mechanism": "IGF2BP2 stabilizes CREB1 mRNA via m6A modification, promoting progression.", "protein": "IGF2BP2", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6M1" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "No direct glycan involvement.", "mechanism": "HMGA2 overexpression activates IGF2BP2, contributing to disease.", "protein": "IGF2BP2", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6M1" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "medium", "disease": "Embryonal rhabdomyosarcoma", "glycan_involvement": "No direct glycan involvement.", "mechanism": "HMGA2 overexpression activates IGF2BP2, contributing to tumorigenesis.", "protein": "IGF2BP2", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6M1" }, "relationship_type": "causal", "source_pmcid": "PMC10915557" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation may affect APLP2 stability and cell surface expression.", "mechanism": "APLP2 upregulation is required for HMGA2/IGF2BP2-driven tumor progression.", "protein": "APLP2", "protein_enriched": { "function": "May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the D", "gene_name": "APLP2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G00912UN", "G02815KT", "G07755XJ", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G31852PQ", "G34989PA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G62765YT", "G64409MC", "G75983OB", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW" ], "uniprot_id": "Q06481" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915557" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation status may influence biomarker utility.", "mechanism": "APLP2 expression correlates with HMGA2 and IGF2BP2 levels and tumor aggressiveness.", "protein": "APLP2", "protein_enriched": { "function": "May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the D", "gene_name": "APLP2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G00912UN", "G02815KT", "G07755XJ", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G31852PQ", "G34989PA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G62765YT", "G64409MC", "G75983OB", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW" ], "uniprot_id": "Q06481" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915557" }, { "confidence": "high", "disease": "Squamous Cell Carcinoma (SCC)", "glycan_involvement": "SCCA is a glycoprotein; glycosylation affects stability and detection.", "mechanism": "Elevated SCCA levels indicate presence and progression of SCC in cervix and vulva.", "protein": "SCCA", "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "high", "disease": "Cervical Cancer", "glycan_involvement": "O-glycosylation modulates P16 stability and cell cycle regulation.", "mechanism": "Strong P16 expression is associated with HPV-driven cervical neoplasia.", "protein": "P16", "protein_enriched": { "function": "Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblas", "gene_name": "CDKN2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42771" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "high", "disease": "HSIL", "glycan_involvement": "Glycosylation influences Ki-67 localization and function.", "mechanism": "High Ki-67 index reflects increased proliferation in high-grade lesions.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "medium", "disease": "Vulvar Cancer", "glycan_involvement": "N-glycosylation regulates EGFR ligand binding and signaling.", "mechanism": "EGFR overexpression promotes tumor growth and progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915755" }, { "confidence": "medium", "disease": "DNA Mismatch Repair Deficiency", "glycan_involvement": "Glycosylation may affect MLH1 stability and repair activity.", "mechanism": "MLH1 expression indicates intact DNA repair; loss leads to genetic instability.", "protein": "MLH1", "protein_enriched": { "function": "Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t", "gene_name": "MLH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P40692" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "medium", "disease": "DNA Mismatch Repair Deficiency", "glycan_involvement": "Glycosylation may modulate PMS2 function.", "mechanism": "PMS2 expression is required for DNA repair; loss increases cancer risk.", "protein": "PMS2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) o", "gene_name": "PMS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54278" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "medium", "disease": "DNA Mismatch Repair Deficiency", "glycan_involvement": "Glycosylation affects MSH2 stability.", "mechanism": "MSH2 is essential for mismatch repair; deficiency leads to tumorigenesis.", "protein": "MSH2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismat", "gene_name": "MSH2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50713DU", "G21891JQ", "G49108TO" ], "uniprot_id": "P43246" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "medium", "disease": "DNA Mismatch Repair Deficiency", "glycan_involvement": "Glycosylation may impact MSH6 function.", "mechanism": "MSH6 partners with MSH2 for DNA repair; loss increases mutation rate.", "protein": "MSH6", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha be", "gene_name": "MSH6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52701" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "high", "disease": "Vascular/Lymphatic Invasion", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell adhesion.", "mechanism": "CD34 marks vascular invasion, indicating aggressive tumor behavior.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "high", "disease": "Lymphatic Invasion", "glycan_involvement": "O-glycosylation critical for podoplanin function in lymphatics.", "mechanism": "D2-40 labels lymphatic vessels invaded by tumor cells.", "protein": "D2-40 (Podoplanin)", "relationship_type": "biomarker", "source_pmcid": "PMC10915755" }, { "confidence": "high", "disease": "Herpes simplex encephalitis", "glycan_involvement": "No direct glycosylation involvement reported for HIF1\u03b1.", "mechanism": "HIF1\u03b1 activation induces autophagy in neurons, restricting HSV replication and limiting inflammation.", "protein": "HIF1\u03b1", "relationship_type": "protective", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "Potential glycoprotein, but glycosylation not discussed in this study.", "mechanism": "BNIP3 is upregulated by HIF1\u03b1, promoting autophagy and antiviral defense in neurons.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "protective", "source_pmcid": "PMC10915869" }, { "confidence": "high", "disease": "Herpes simplex encephalitis", "glycan_involvement": "No glycosylation involvement reported.", "mechanism": "ATG5-dependent autophagy is essential for HIF-mediated antiviral activity; ATG5 deficiency impairs viral control.", "protein": "ATG5", "relationship_type": "causal", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "HSV-2 meningitis", "glycan_involvement": "VEGFA is a glycoprotein, but glycosylation not mechanistically discussed here.", "mechanism": "VEGFA is a HIF target gene, upregulated during hypoxia and infection; may reflect HIF pathway activation.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "Brain inflammation", "glycan_involvement": "CXCL10 is a glycoprotein, but glycosylation not mechanistically discussed here.", "mechanism": "CXCL10 levels increase with elevated inflammation in HIF-deficient mice after HSV infection.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "No glycosylation involvement reported.", "mechanism": "LC3B conversion (autophagy marker) is induced by HIF activation, mediating antiviral defense.", "protein": "LC3B", "protein_enriched": { "function": "Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes) (PubMed:20418806, PubMed:23209295, PubMed:28017329). Plays a role in mitophagy which contributes to regulate m", "gene_name": "MAP1LC3B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9GZQ8" }, "relationship_type": "protective", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "Brain inflammation", "glycan_involvement": "STING is glycosylated, but glycosylation not discussed in this study.", "mechanism": "STING pathway activation is elevated in HIF-deficient neurons, leading to increased inflammation.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "causal", "source_pmcid": "PMC10915869" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "HIF1\u03b1 activation restricts viral replication and limits inflammatory response in CNS.", "protein": "HIF1\u03b1", "relationship_type": "protective", "source_pmcid": "PMC10915869" }, { "confidence": "low", "disease": "Herpes simplex encephalitis", "glycan_involvement": "Potential glycoprotein, but glycosylation not discussed.", "mechanism": "BNIP3L upregulated by HIF1\u03b1, promotes autophagy and antiviral defense.", "protein": "BNIP3L", "protein_enriched": { "function": "Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits ", "gene_name": "BNIP3L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60238" }, "relationship_type": "protective", "source_pmcid": "PMC10915869" }, { "confidence": "low", "disease": "Herpes simplex encephalitis", "glycan_involvement": "ENO1 is not a glycoprotein.", "mechanism": "ENO1 is a HIF target gene, upregulated during hypoxia and infection; reflects HIF pathway activation.", "protein": "ENO1", "relationship_type": "biomarker", "source_pmcid": "PMC10915869" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation stabilizes catalase and enhances its activity.", "mechanism": "Catalase reduces oxidative stress by decomposing hydrogen peroxide, protecting pancreatic beta cells.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects catalase secretion and stability in tumor cells.", "mechanism": "Catalase modulates tumor microenvironment by reducing ROS, limiting cancer cell proliferation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915913" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation is required for proper localization and activity in vascular tissues.", "mechanism": "Catalase prevents endothelial dysfunction by detoxifying hydrogen peroxide.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Neurodegenerative Diseases", "glycan_involvement": "Glycosylation influences catalase stability in neural tissues.", "mechanism": "Catalase reduces neuronal oxidative damage, slowing neurodegeneration.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Glycosylation modulates immune cell catalase activity.", "mechanism": "Catalase lowers ROS-mediated inflammation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is essential for catalase function in vascular cells.", "mechanism": "Catalase prevents lipid peroxidation and plaque formation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Liver Disease", "glycan_involvement": "Glycosylation affects hepatic catalase stability.", "mechanism": "Catalase detoxifies peroxides, protecting hepatocytes.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Renal Disease", "glycan_involvement": "Glycosylation maintains catalase activity in kidneys.", "mechanism": "Catalase reduces oxidative injury in renal tissues.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Glycosylation preserves catalase function during aging.", "mechanism": "Catalase delays cellular aging by limiting ROS accumulation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC10915913" }, { "confidence": "high", "disease": "Oxidative Stress-related Disorders", "glycan_involvement": "Glycosylation enhances catalase stability and activity.", "mechanism": "Catalase mitigates oxidative damage in various tissues.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10915913" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation stabilizes IFNGR1 and is necessary for IFN-\u03b3 signaling.", "mechanism": "Reduced IFNGR1 expression desensitizes IFN-\u03b3 signaling, promoting LUAD progression and poor antiviral defense.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10915940" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation affects IFNGR1 stability and antiviral function.", "mechanism": "Low IFNGR1 in LUAD increases susceptibility to SARS-CoV-2 due to impaired IFN-\u03b3 antiviral response.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "causal/protective", "source_pmcid": "PMC10915940" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "ACE-2 is a glycoprotein; glycosylation affects viral spike binding and cell entry.", "mechanism": "ACE-2 is upregulated in LUAD, increasing risk of SARS-CoV-2 infection.", "protein": "ACE-2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10915940" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation stabilizes IFNGR1 and supports antitumor IFN-\u03b3 signaling.", "mechanism": "High IFNGR1 expression correlates with longer survival; loss promotes tumor progression.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation supports IFNGR1 stability and function.", "mechanism": "Elevated IFNGR1 linked to tumor rejection; reduced levels associated with recurrence.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation maintains IFNGR1 stability.", "mechanism": "High IFNGR1 expression predicts better survival; loss leads to poor prognosis.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Not specified.", "mechanism": "IFNGR1 promoter polymorphisms increase risk of gastric cancer.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Rectal cancer", "glycan_involvement": "Not specified.", "mechanism": "IFNGR1 polymorphisms (rs3799488, rs2234711) associated with increased risk and survival outcomes.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Leishmaniasis/Tuberculosis", "glycan_involvement": "Not specified.", "mechanism": "IFNGR1 polymorphisms increase susceptibility to these infections.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "causal/protective", "source_pmcid": "PMC10915940" }, { "confidence": "medium", "disease": "Castration-resistant prostate cancer", "glycan_involvement": "MUC1 is heavily O-glycosylated; glycosylation modulates its function and interactions.", "mechanism": "MUC1 regulates IFNGR1 expression and degradation, influencing EMT and oncogenesis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC10915940" }, { "confidence": "high", "disease": "Androgenic alopecia", "glycan_involvement": "CD34 is a heavily glycosylated transmembrane protein; glycosylation is essential for its cell surface expression and function.", "mechanism": "CD34 marks HFSCs involved in hair regeneration; loss of HFSC function leads to follicle miniaturization.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC10915958" }, { "confidence": "high", "disease": "Alopecia areata", "glycan_involvement": "CD200 is a glycoprotein; glycosylation may affect receptor binding and immunomodulatory function.", "mechanism": "CD200 attenuates inflammatory reactions and promotes immune tolerance in hair follicles; downregulation is linked to autoimmune hair loss.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "protective", "source_pmcid": "PMC10915958" }, { "confidence": "high", "disease": "Inflammation (perifollicular/intrafollicular)", "glycan_involvement": "Glycosylation of CD200 may modulate its immunoregulatory activity.", "mechanism": "CD200 deficiency leads to increased T cell infiltration and inflammation around hair follicles.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "high", "disease": "Hair follicle miniaturization", "glycan_involvement": "Lgr5 is a glycoprotein receptor; glycosylation may affect ligand binding and Wnt signaling.", "mechanism": "Loss of Lgr5+ stem cells abolishes hair regeneration; restoration reverses miniaturization.", "protein": "Lgr5", "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Impaired wound healing", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Lhx2 heterozygous mutations slow wound healing and impair HFSC function.", "protein": "Lhx2", "protein_enriched": { "function": "Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix", "gene_name": "THSD1", "glycan_count": 2, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G53434XO" ], "uniprot_id": "Q9NS62" }, "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Hair follicle miniaturization", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Reduced Foxc1 expression in aged mice leads to HFSC escape and follicle miniaturization.", "protein": "Foxc1", "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Hair follicle miniaturization", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Reduced Nfatc1 expression in aged mice contributes to HFSC escape and hair loss.", "protein": "Nfatc1", "protein_enriched": { "function": "Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Cou", "gene_name": "NFATC1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95644" }, "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Hair follicle cycle defects", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Runx1 ablation blocks hair regeneration and prolongs telogen phase.", "protein": "Runx1", "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Hair regeneration defect", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Overexpression of Musashi 2 impairs hair cell regeneration and prolongs telogen.", "protein": "Musashi 2", "relationship_type": "causal", "source_pmcid": "PMC10915958" }, { "confidence": "medium", "disease": "Androgenic alopecia", "glycan_involvement": "Keratin proteins are not glycosylated; no glycan involvement.", "mechanism": "K15 marks HFSCs in the bulge; loss of these cells is associated with hair loss.", "protein": "K15", "relationship_type": "biomarker", "source_pmcid": "PMC10915958" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Nav\u03b23 is a glycoprotein; glycosylation may affect trafficking and membrane localization, but specific glycan changes not detailed.", "mechanism": "SCN3B P87l mutation reduces cell surface expression and sodium current, altering cardiac action potentials and increasing arrhythmia risk.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Nav1.5 is a glycoprotein; glycosylation may regulate channel trafficking, but no specific glycan modification described.", "mechanism": "Reduced membrane localization and expression of Nav1.5 due to SCN3B mutation decreases sodium current, contributing to arrhythmogenesis.", "protein": "Nav1.5 (SCN5A)", "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation may influence channel function and localization; not specifically addressed for these mutations.", "mechanism": "SCN3B mutations (e.g., L10P, R6K, M161T) reduce sodium current, predisposing to atrial fibrillation.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "medium", "disease": "Idiopathic ventricular fibrillation", "glycan_involvement": "Glycosylation may affect channel properties; not specifically discussed for this mutation.", "mechanism": "SCN3B V54G mutation decreases sodium current and alters inactivation, leading to ventricular fibrillation.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Glycosylation status may affect detection and function; not directly discussed.", "mechanism": "SCN3B mutations (P87l, L10P, V110l) are associated with BrS and can serve as genetic biomarkers.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Glycosylation may modulate channel function; not specifically addressed.", "mechanism": "SCN5A mutations are frequently found in BrS patients and correlate with disease severity.", "protein": "Nav1.5 (SCN5A)", "relationship_type": "biomarker", "source_pmcid": "PMC10916001" }, { "confidence": "medium", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Potential for glycan-targeted therapies to improve trafficking; not experimentally tested.", "mechanism": "Restoring membrane localization or function of Nav\u03b23 may ameliorate sodium current deficits in BrS.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916001" }, { "confidence": "medium", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Glycosylation may be a modifiable factor for channel expression; not directly studied.", "mechanism": "Targeting Nav1.5 trafficking or function could reduce arrhythmia risk in BrS.", "protein": "Nav1.5 (SCN5A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Glycosylation may affect channel stability and localization; not specifically analyzed.", "mechanism": "Loss-of-function mutations in SCN3B decrease sodium current, facilitating phase-2 reentry and arrhythmogenesis.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Brugada syndrome (BrS)", "glycan_involvement": "Glycosylation may regulate membrane trafficking; not directly implicated in this mutation.", "mechanism": "SCN3B P87l mutation causes redistribution from membrane to cytoplasm, reducing functional sodium channels.", "protein": "Nav\u03b23 (SCN3B)", "protein_enriched": { "function": "Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (volta", "gene_name": "SCN3B", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY72" }, "relationship_type": "causal", "source_pmcid": "PMC10916001" }, { "confidence": "high", "disease": "Renal cell carcinoma", "glycan_involvement": "CD147 is a glycoprotein; glycosylation is essential for its function and EV incorporation.", "mechanism": "CD147-positive EVs are significantly elevated in plasma of renal cancer patients, especially at early stages; these EVs are miRNA-rich and reflect tumor miRNA signatures.", "protein": "CD147 (EMMPRIN/basigin)", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "CD147 glycosylation facilitates its EV localization and interaction with miRNA sorting machinery.", "mechanism": "CD147-positive EVs are increased in ovarian cancer patients and are enriched in miRNA, improving diagnostic sensitivity.", "protein": "CD147 (EMMPRIN/basigin)", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation of CD147 is required for its surface expression and EV incorporation.", "mechanism": "Elevated circulating CD147-positive EVs detected in colorectal cancer patients from earliest stages.", "protein": "CD147 (EMMPRIN/basigin)", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation modulates CD147 function and EV targeting.", "mechanism": "CD147 is enriched in pancreatic tumor-derived EVs compared to normal tissue EVs.", "protein": "CD147 (EMMPRIN/basigin)", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "CD24 is mucin-like and heavily glycosylated, affecting its immune recognition and EV sorting.", "mechanism": "CD24-positive EVs detected in body fluids of breast cancer patients; however, specificity is limited due to expression in normal cells.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation impacts CD24's role in EV biology.", "mechanism": "CD24-positive EVs found in ovarian cancer patient fluids, but also in healthy subjects.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Proteoglycan structure (heparan sulfate chains) is critical for EV association.", "mechanism": "Glypican-1-positive EVs distinguish pancreatic cancer patients from healthy and benign disease; however, also secreted by fibroblasts.", "protein": "Glypican-1", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "EpCAM glycosylation affects stability and immune capture.", "mechanism": "EpCAM-positive EVs elevated in colorectal cancer; ectodomain cleavage may limit detection.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "high", "disease": "Glioblastoma multiforme", "glycan_involvement": "EGFR glycosylation influences receptor function and EV incorporation.", "mechanism": "EGFRvIII detected in EVs from glioma cells and patient plasma; specific to glioblastoma.", "protein": "EGFRvIII", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "CD98 glycosylation modulates EV association.", "mechanism": "CD98-positive EVs released by renal cancer cells are miRNA-rich, though less so than CD147-positive EVs.", "protein": "CD98", "relationship_type": "biomarker", "source_pmcid": "PMC10916008" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding; mutations (e.g., D614G) increase transmissibility and virulence.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but interacts with glycosylated host proteins.", "mechanism": "Removes ADP-ribose from host proteins to counteract antiviral response; Pakistani variants (M265I, G307C, L357I) reduce ADPr binding, lowering virulence.", "protein": "Nsp3 Macrodomain-1 (Mac-1)", "relationship_type": "causal/protective", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but modulates host glycoprotein signaling.", "mechanism": "Binds G-quadruplexes in host mRNAs, disrupting antiviral signaling; mutations may affect immune evasion.", "protein": "Nsp3 Macrodomain-2 (Mac-2)", "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but influences host glycoprotein-mediated pathways.", "mechanism": "Interacts with host E3 ligase RCHY1, promoting p53 degradation and delaying immune gene activation.", "protein": "Nsp3 Macrodomain-3 (Mac-3)", "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects membrane localization and immune recognition.", "mechanism": "Essential for viral assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation modulates host immune response.", "mechanism": "Involved in virus assembly and release.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "May be O-glycosylated, affecting immune detection.", "mechanism": "Major structural protein; used in diagnostics.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but interacts with host glycoproteins.", "mechanism": "Processes viral polyproteins and antagonizes host immune response.", "protein": "Papain-like protease (PL2pro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation implicated in immune modulation.", "mechanism": "Modulates immune evasion and inflammation.", "protein": "ORF8 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation affects function.", "mechanism": "Involved in viral pathogenicity and apoptosis.", "protein": "ORF3a glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC10916261" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N- and O-glycosylation changes serve as diagnostic/prognostic markers", "mechanism": "Altered glycosylation profile in severe COVID-19 (increased Lewis x, decreased Lewis y, decreased highly branched N-glycans, increased core 3 O-glycans)", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Fucosylation of N-glycans (Lewis x) increases in severe disease", "mechanism": "Higher expression of Lewis x oligosaccharide structures in severe COVID-19 patients", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Fucosylation of N-glycans (Lewis y) decreases during recovery", "mechanism": "Lower expression of Lewis y structures in convalescents compared to patients and controls", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Reduced branching of N-glycans associated with disease progression", "mechanism": "Lowest expression of highly branched N-glycans in severe COVID-19", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Increased expression of core 3 O-glycans in IgG during disease and recovery", "mechanism": "Higher reactivity of IgG O-glycans with Jacalin in COVID-19 and convalescents", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Agalactosylated and asialylated N-glycans promote disease severity", "mechanism": "Reduced galactosylation and sialylation of IgG activates effector cells and inflammation", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10916521" }, { "confidence": "medium", "disease": "Crohn\u2019s disease", "glycan_involvement": "Changes in N-glycan fucosylation and branching", "mechanism": "Altered fucosylation and glycosylation patterns in IgG", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10916521" }, { "confidence": "medium", "disease": "Lupus erythematosus", "glycan_involvement": "Agalactosylated/asialylated N-glycans", "mechanism": "Reduced galactosylation and sialylation of IgG triggers inflammation", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10916521" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Increased branching and sialylation of N-glycans", "mechanism": "Elevated expression of highly branched N-glycans in acute phase glycoproteins", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "medium", "disease": "Cytomegalovirus infection", "glycan_involvement": "Loss of core fucose increases cytotoxicity", "mechanism": "Production of afucosylated IgG enhances ADCC via Fc\u03b3RIIIa", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC10916521" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "GP6 is a glycoprotein involved in platelet activation and tumor microenvironment.", "mechanism": "MGF downregulates GP6 signaling, reducing tumor invasion and angiogenesis.", "protein": "GP6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "MMP-2 glycosylation affects secretion and activity in ECM remodeling.", "mechanism": "MGF downregulates MMP-2, inhibiting cellular proliferation and migration.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "MMP-9 glycosylation modulates enzyme stability and tumor invasion.", "mechanism": "MGF downregulates MMP-9, reducing tumor progression and metastasis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "VEGF glycosylation is critical for receptor binding and angiogenic signaling.", "mechanism": "MGF suppresses VEGF gene expression, inhibiting angiogenesis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Bcl-2 glycosylation may affect its anti-apoptotic function.", "mechanism": "MGF downregulates Bcl-2, promoting apoptosis in cancer cells.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Caspase-3 glycosylation can regulate its activation.", "mechanism": "MGF induces Caspase-3 activation, leading to DNA degradation and apoptosis.", "protein": "CASP3", "relationship_type": "biomarker", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Leukemia (AML)", "glycan_involvement": "CD3 glycosylation is essential for T-cell receptor function.", "mechanism": "MGF increases CD3+ T cells, enhancing immune response against leukemia.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Leukemia (AML)", "glycan_involvement": "CD19 glycosylation affects B-cell activation and signaling.", "mechanism": "MGF increases CD19+ B cells, supporting humoral immunity.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Leukemia (AML)", "glycan_involvement": "CD11b glycosylation modulates cell adhesion and migration.", "mechanism": "MGF decreases CD11b+ monocytes, reducing inflammation and tumor support.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916574" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "WT1 glycosylation may regulate nuclear localization and transcriptional activity.", "mechanism": "MGF downregulates LEF1 via WT1, inhibiting Wnt signaling and tumor growth.", "protein": "WT1", "protein_enriched": { "function": "Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:17716689, PubMed:2525", "gene_name": "WT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19544" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916574" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "GLUT-4 is a glycoprotein; glycosylation is essential for its trafficking and function.", "mechanism": "Upregulation of GLUT-4 expression improves glucose uptake and insulin sensitivity.", "protein": "GLUT-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916669" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects GLUT-4 membrane localization and activity.", "mechanism": "Increased GLUT-4 expression reduces hyperglycemia and adiposity.", "protein": "GLUT-4", "relationship_type": "protective", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "No direct glycosylation involvement; included for pathway relevance.", "mechanism": "Upregulation of PPAR-\u03b3 promotes adipocyte differentiation and improves lipid metabolism.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916669" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "No direct glycosylation involvement; enzyme activity is regulated by other mechanisms.", "mechanism": "Downregulation reduces cholesterol biosynthesis.", "protein": "HMG-CoA reductase", "protein_enriched": { "function": "Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in c", "gene_name": "HMGCR", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G46503DX", "G48584BU", "G62765YT", "G64527OM", "G70101JE", "G49108TO", "G80920RR" ], "uniprot_id": "P04035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "No direct glycosylation involvement; included for pathway relevance.", "mechanism": "Upregulation of iNOS promotes inflammation and insulin resistance.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "No direct glycosylation involvement; included for tissue injury relevance.", "mechanism": "Elevated caspase-3 indicates increased apoptosis in liver tissue.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916669" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation is required for GLUT-4 stability and function.", "mechanism": "Enhanced GLUT-4 expression improves lipid profile by promoting glucose utilization.", "protein": "GLUT-4", "relationship_type": "protective", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Kidney dysfunction", "glycan_involvement": "Glycosylation affects GLUT-4 targeting in renal tissues.", "mechanism": "Improved GLUT-4 expression may ameliorate renal glucose handling.", "protein": "GLUT-4", "relationship_type": "protective", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation is necessary for GLUT-4 function in hepatocytes.", "mechanism": "Upregulation reduces hepatic fat accumulation and improves liver function.", "protein": "GLUT-4", "relationship_type": "protective", "source_pmcid": "PMC10916669" }, { "confidence": "medium", "disease": "Kidney dysfunction", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Suppression of caspase-3 reduces apoptosis in kidney tissue.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916669" }, { "confidence": "high", "disease": "Drug resistance in lung cancer", "glycan_involvement": "Glycosylation is essential for P-gp folding, stability, and membrane localization.", "mechanism": "P-gp acts as a drug efflux pump, reducing intracellular concentrations of chemotherapeutics and causing multidrug resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC10916800" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and receptor activation.", "mechanism": "Mutations in EGFR drive NSCLC; EGFR is targeted by tyrosine kinase inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation affects PD-1 surface expression and ligand binding.", "mechanism": "PD-1 is targeted by immune checkpoint inhibitors to enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 expression on tumor cells suppresses immune response; targeted by checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation regulates CTLA-4 trafficking and function.", "mechanism": "CTLA-4 blockade can trigger or worsen autoimmune diseases during cancer immunotherapy.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation affects MMP9 secretion and activity.", "mechanism": "MMP9 promotes angiogenesis and metastasis in lung cancer.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC10916800" }, { "confidence": "low", "disease": "Lung cancer", "glycan_involvement": "Not specified in article.", "mechanism": "Cyclin D1 activity promotes cell cycle progression and tumor growth.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "causal", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Bacterial glycoproteins degrade host mucins, modulating immune response.", "mechanism": "Presence of A. muciniphila in gut microbiome predicts better response to immune checkpoint inhibitors.", "protein": "Akkermansia muciniphila (mucin-degrading glycoproteins)", "relationship_type": "protective", "source_pmcid": "PMC10916800" }, { "confidence": "medium", "disease": "Drug resistance in lung cancer", "glycan_involvement": "Glycosylation is required for P-gp function.", "mechanism": "Verapamil inhibits P-gp, reversing drug resistance and improving chemotherapy efficacy.", "protein": "Verapamil target (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10916800" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates PD-1 function.", "mechanism": "Obesity increases PD-1 expression via leptin, potentially enhancing response to PD-1 inhibitors.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC10916800" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for ACVR2B directly.", "mechanism": "Serum autoantibody response (IgG) to ACVR2B is part of a biomarker panel for PDAC diagnosis.", "protein": "ACVR2B", "protein_enriched": { "function": "Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activi", "gene_name": "ACVR2B", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G27058EU" ], "uniprot_id": "Q13705" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for GAGE1 directly.", "mechanism": "Serum autoantibody response (IgG and IgA) to GAGE1 is part of biomarker panels for PDAC.", "protein": "GAGE1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13067" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for LEMD1 directly.", "mechanism": "Serum autoantibody response (IgG) to LEMD1 is part of a biomarker panel for PDAC.", "protein": "LEMD1", "protein_enriched": { "function": "Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis (PubMed:163", "gene_name": "LEMD2", "glycan_count": 10, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G02815KT", "G23719VF", "G31852PQ", "G41247ZX", "G62765YT", "G95177YH", "G98611JV", "G42124LM", "G49108TO" ], "uniprot_id": "Q8NC56" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for MAGEB1 directly.", "mechanism": "Serum autoantibody response (IgG) to MAGEB1 is part of a biomarker panel for PDAC.", "protein": "MAGEB1", "protein_enriched": { "function": "Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances ubiquitin ligase activity of TRIM28 and stimulates p53/TP53 ubiquitina", "gene_name": "MAGEC2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBF1" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for PAGE1 directly.", "mechanism": "Serum autoantibody response (IgG) to PAGE1 is part of a biomarker panel for PDAC.", "protein": "PAGE1", "protein_enriched": { "function": "Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot", "gene_name": "ATP6V0A4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HBG4" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for AURKA directly.", "mechanism": "Serum autoantibody response (IgA) to AURKA is part of a biomarker panel for PDAC.", "protein": "AURKA", "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for MAGEA10 directly.", "mechanism": "Serum autoantibody response (IgA) to MAGEA10 is part of a biomarker panel for PDAC.", "protein": "MAGEA10", "protein_enriched": { "function": "Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium", "gene_name": "CEP41", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BYV8" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for PLEKHA5 directly.", "mechanism": "Serum autoantibody response (IgA) to PLEKHA5 is part of a biomarker panel for PDAC.", "protein": "PLEKHA5", "protein_enriched": { "function": "", "gene_name": "TCP11L1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NUJ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Not specified for XAGE3aV1 directly.", "mechanism": "Serum autoantibody response (IgA) to XAGE3aV1 is part of a biomarker panel for PDAC.", "protein": "XAGE3aV1", "protein_enriched": { "function": "Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression ", "gene_name": "RARG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13631" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Increased sialylation (\u03b12,6-linked) on IgA in PDAC, associated with immune suppression.", "mechanism": "IgA autoantibodies (especially IgA2 subclass) are locally produced in PDAC tissue, contributing to a pro-inflammatory yet immune-tolerant microenvironment.", "protein": "IgA (autoantibody)", "relationship_type": "immune suppressive phenotype", "source_pmcid": "PMC10917065" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "PLAUR is a glycoprotein; glycosylation may affect cell adhesion and immune signaling.", "mechanism": "Downregulated in GDM; correlates positively with naive B cell infiltration, suggesting immune regulatory involvement.", "protein": "PLAUR", "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "SLIT2 is a secreted glycoprotein; glycosylation may modulate its anti-inflammatory and metabolic effects.", "mechanism": "Downregulated in GDM; correlates negatively with T follicular helper cell infiltration, involved in inflammatory response and glucose metabolism.", "protein": "SLIT2", "protein_enriched": { "function": "Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navig", "gene_name": "SLIT2", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G42124LM", "G80920RR", "G62765YT", "G41071NU", "G87661QW", "G83646BJ", "G79208PO", "G88520YF", "G37412TK", "G49906RN", "G65184UU", "G83460ZZ", "G49108TO" ], "uniprot_id": "O94813" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation may influence stability and activity.", "mechanism": "Upregulated in GDM; associated with metabolic processes and oxidative stress.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation may affect secretion and receptor interaction.", "mechanism": "Upregulated in GDM; involved in embryonic development and vascular regulation.", "protein": "BMP4", "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation may modulate cell-cell interactions.", "mechanism": "Upregulated in GDM; involved in cell signaling and vascular development.", "protein": "EFNB2", "protein_enriched": { "function": "Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.", "gene_name": "EFNB2", "glycan_count": 17, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41071NU", "G45395BF", "G57321FI", "G11629QQ", "G01650EU", "G06356OH", "G15169WU", "G22310AV", "G29299MO", "G40834TG", "G41247ZX", "G47518TP", "G48414YA", "G59536GA", "G60967DT", "G82830MN", "G49108TO" ], "uniprot_id": "P52799" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Glycosylation may affect enzymatic activity.", "mechanism": "Downregulated in GDM; involved in peptide metabolism and vascular function.", "protein": "MME", "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Regulates cell adhesion and immune response, potentially influencing insulin resistance.", "protein": "PLAUR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917066" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects anti-inflammatory activity.", "mechanism": "Circulating SLIT2 negatively correlates with serum glucose; may protect against hyperglycemia.", "protein": "SLIT2", "protein_enriched": { "function": "Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navig", "gene_name": "SLIT2", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G42124LM", "G80920RR", "G62765YT", "G41071NU", "G87661QW", "G83646BJ", "G79208PO", "G88520YF", "G37412TK", "G49906RN", "G65184UU", "G83460ZZ", "G49108TO" ], "uniprot_id": "O94813" }, "relationship_type": "protective", "source_pmcid": "PMC10917066" }, { "confidence": "low", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation influences cell motility and adhesion.", "mechanism": "Involved in angiogenesis and vascular remodeling, processes relevant to CVD.", "protein": "PLAUR", "relationship_type": "causal", "source_pmcid": "PMC10917066" }, { "confidence": "low", "disease": "Systemic Scleroderma", "glycan_involvement": "Glycosylation may modulate extracellular matrix interactions.", "mechanism": "Enriched in disease ontology analysis; may regulate inflammation and fibrosis.", "protein": "SLIT2", "protein_enriched": { "function": "Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navig", "gene_name": "SLIT2", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G42124LM", "G80920RR", "G62765YT", "G41071NU", "G87661QW", "G83646BJ", "G79208PO", "G88520YF", "G37412TK", "G49906RN", "G65184UU", "G83460ZZ", "G49108TO" ], "uniprot_id": "O94813" }, "relationship_type": "biomarker", "source_pmcid": "PMC10917066" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "PAI-1 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "Elevated PAI-1 levels inhibit fibrinolysis, promoting thrombus stability and atherosclerosis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "high", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Glycosylation modulates PAI-1 activity and plasma levels.", "mechanism": "4G/4G PAI-1 polymorphism increases PAI-1 expression, raising MI risk via impaired fibrinolysis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "High PAI-1 levels due to 4G/4G genotype increase risk of thrombotic events.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "medium", "disease": "Peripheral Artery Disease (PAD)", "glycan_involvement": "Glycosylation affects PAI-1 stability and function.", "mechanism": "Elevated PAI-1 impairs fibrinolysis, contributing to PAD development.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "medium", "disease": "Cerebrovascular Disease", "glycan_involvement": "Glycosylation influences circulating levels.", "mechanism": "High PAI-1 levels increase risk of cerebrovascular thrombosis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "MTHFR mutation leads to hyperhomocysteinemia, causing endothelial damage and promoting CAD.", "protein": "MTHFR", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "medium", "disease": "Peripheral Artery Disease (PAD)", "glycan_involvement": "None.", "mechanism": "Hyperhomocysteinemia from MTHFR mutation increases PAD risk.", "protein": "MTHFR", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "medium", "disease": "Cerebrovascular Disease", "glycan_involvement": "None.", "mechanism": "Elevated homocysteine damages endothelium, increasing cerebrovascular disease risk.", "protein": "MTHFR", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "high", "disease": "Homocystinuria", "glycan_involvement": "None.", "mechanism": "MTHFR mutation impairs homocysteine metabolism, causing homocystinuria.", "protein": "MTHFR", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "medium", "disease": "Cardiogenic Shock", "glycan_involvement": "Glycosylation required for PAI-1 function.", "mechanism": "High PAI-1 levels (4G/4G genotype) contribute to severe CAD and MI, leading to cardiogenic shock.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC10917360" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Defects in N-glycan assembly/transfer (CDG-I) cause cardiac dysfunction.", "mechanism": "Defective N-glycosylation impairs cardiac protein function, leading to DCM.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy", "glycan_involvement": "N-glycosylation defects in CDG affect cardiac muscle proteins.", "mechanism": "Abnormal N-glycosylation disrupts cardiac muscle protein structure.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "O-glycosylation pathway defects in CDG contribute to DCM.", "mechanism": "O-glycosylation defects impair cardiac glycoprotein function.", "protein": "O-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Dolichol-linked glycosylation defects in CDG cause DCM.", "mechanism": "Dolichol biosynthesis defects disrupt glycoprotein maturation, affecting cardiac function.", "protein": "Dolichol pathway proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "medium", "disease": "Structural Heart Disease", "glycan_involvement": "GPI anchor glycosylation defects in CDG cause structural heart defects.", "mechanism": "Defective GPI anchor biosynthesis leads to abnormal cardiac septal/valvular development.", "protein": "GPI-anchored proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "medium", "disease": "Structural Heart Disease", "glycan_involvement": "COG complex glycosylation defects in CDG cause septal/valvular abnormalities.", "mechanism": "COG complex defects impair Golgi glycoprotein processing, affecting heart structure.", "protein": "COG complex proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "low", "disease": "Pericardial Effusion", "glycan_involvement": "N-glycosylation defects in CDG contribute to pericardial effusion.", "mechanism": "Impaired glycosylation affects cardiac extracellular matrix proteins, leading to effusion.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "low", "disease": "Rhythm Disturbances", "glycan_involvement": "N-glycosylation defects in CDG affect cardiac conduction proteins.", "mechanism": "Glycosylation defects alter ion channel glycoproteins, predisposing to arrhythmias.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "low", "disease": "Acute Myocarditis", "glycan_involvement": "N-glycosylation defects in CDG may impair immune regulation in myocardium.", "mechanism": "Underlying glycosylation defects may predispose to immune-mediated myocardial inflammation.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation defects in CDG cause multisystem and cardiac failure.", "mechanism": "Global impairment of glycoprotein function leads to cardiac dysfunction and failure.", "protein": "N-glycosylated proteins", "relationship_type": "causal", "source_pmcid": "PMC10917471" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation increases stability and efficacy of recombinant IL-7.", "mechanism": "IL-7 boosts T cell immunity, increases tumor-infiltrating lymphocytes, and inhibits T cell exhaustion.", "protein": "IL-7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Fc fusion and glycosylation prolong half-life and enhance immune effects.", "mechanism": "Fc-fused glycosylated IL-7 increases CD8 T cell infiltration and antitumor activity, especially in immunogenic tumors.", "protein": "IL-7-hyFc (efineptakin alfa)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation improves half-life and reduces immunogenicity.", "mechanism": "Expands CD4 and CD8 T cells, improves gut barrier integrity, but may expand HIV reservoir.", "protein": "CYT107 (glycosylated IL-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "Idiopathic CD4 lymphocytopenia (ICL)", "glycan_involvement": "Glycosylation improves pharmacokinetics and tolerability.", "mechanism": "Increases circulating and tissue-resident CD4/CD8 T cells, improves clinical outcomes.", "protein": "CYT107 (glycosylated IL-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "medium", "disease": "Progressive multifocal leukoencephalopathy (PML)", "glycan_involvement": "Glycosylation improves stability and immune response.", "mechanism": "Enhances JC virus-specific immune response, stabilizes lesions, reduces viral load.", "protein": "CYT107 (glycosylated IL-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation improves safety and half-life.", "mechanism": "Reverses T cell loss, improves immune effector function without cytokine storm.", "protein": "CYT107 (glycosylated IL-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation improves pharmacokinetics and tolerability.", "mechanism": "Restores CD4/CD8 T cell numbers, improves immune function.", "protein": "CYT107 (glycosylated IL-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "Bone marrow transplantation (BMT)/HSCT", "glycan_involvement": "Fc fusion and glycosylation enhance mobilization and immune recovery.", "mechanism": "Promotes immune reconstitution post-transplant, mobilizes hematopoietic stem cells.", "protein": "IL-7-hyFc (efineptakin alfa)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "medium", "disease": "Acute respiratory infections", "glycan_involvement": "Glycosylation and Fc fusion improve tissue targeting and efficacy.", "mechanism": "Long-acting glycosylated IL-7 increases innate-like T cells, enhances antiviral and antibacterial immunity.", "protein": "IL-7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10917577" }, { "confidence": "medium", "disease": "Graft versus host disease (GVHD)", "glycan_involvement": "Glycosylation improves safety profile.", "mechanism": "IL-7 administration post-BMT does not worsen GVHD while maintaining graft-versus-leukemia activity.", "protein": "IL-7", "relationship_type": "protective", "source_pmcid": "PMC10917577" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "O-fucosylation of NOTCH EGF-like domains by POFUT1 modulates NOTCH signaling, impacting immune cell development and tumor microenvironment.", "mechanism": "High POFUT1 expression correlates with poor prognosis and increased infiltration of immunosuppressive M2 macrophages/M2-like TAMs.", "protein": "POFUT1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10923674" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "O-fucosylation of NOTCH receptors; functional impact less clear in GBM than LGG.", "mechanism": "POFUT1 is upregulated in GBM, but its expression does not significantly correlate with prognosis.", "protein": "POFUT1", "relationship_type": "biomarker", "source_pmcid": "PMC10923674" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "O-fucosylation of NOTCH pathway components regulates cell survival.", "mechanism": "Suppression of POFUT1 leads to increased apoptosis and reduced proliferation of tumor cells.", "protein": "POFUT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10923674" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-fucosylation of NOTCH pathway glycoproteins influences metastatic potential.", "mechanism": "High POFUT1 expression correlates with lymph node metastasis and advanced stage.", "protein": "POFUT1", "relationship_type": "biomarker", "source_pmcid": "PMC10923674" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "O-fucosylation of EGF-like domains in glycoproteins.", "mechanism": "Distinct expression pattern suggests potential as a biomarker or target.", "protein": "POFUT1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10923674" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "O-fucosylation of NOTCH and related glycoproteins.", "mechanism": "POFUT1 overexpression promotes malignant phenotype and perineural invasion.", "protein": "POFUT1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC10923674" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "O-fucosylation of NOTCH receptors modulates pathway activation.", "mechanism": "POFUT1 promotes progression via Notch/Wnt signaling pathways.", "protein": "POFUT1", "relationship_type": "causal", "source_pmcid": "PMC10923674" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "O-fucosylation of NOTCH1 EGF-like domains is essential for receptor function.", "mechanism": "NOTCH1 activation (regulated by POFUT1-mediated O-fucosylation) promotes tumorigenesis and chemoresistance.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC10923674" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "Glycosylation status not specified, but marker for M2 macrophage phenotype.", "mechanism": "CD163+ M2 macrophages promote immunosuppression and tumor progression; infiltration correlates with high POFUT1.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "causal", "source_pmcid": "PMC10923674" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "Glycosylation status not specified, but marker for TAM phenotype.", "mechanism": "CD68+ M2-like TAMs contribute to immunosuppressive microenvironment and poor prognosis; infiltration correlates with high POFUT1.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "causal", "source_pmcid": "PMC10923674" }, { "confidence": "high", "disease": "Peritoneal Tuberculosis", "glycan_involvement": "CA-125 is heavily glycosylated; glycosylation affects its secretion and detection.", "mechanism": "Elevated CA-125 reflects peritoneal inflammation and mesothelial cell activation in TB.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "high", "disease": "Ovarian Malignancy", "glycan_involvement": "Glycosylation is critical for CA-125's antigenicity and serum stability.", "mechanism": "CA-125 is released by malignant ovarian epithelial cells, especially with peritoneal dissemination.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation modulates immune recognition and clearance.", "mechanism": "Elevated CA-125 due to ectopic endometrial tissue and peritoneal irritation.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "medium", "disease": "Endometrial Cancer", "glycan_involvement": "Altered glycosylation may affect tumor progression and immune evasion.", "mechanism": "CA-125 may be elevated due to tumor invasion of uterine serosa.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "low", "disease": "Functional Ovarian Cyst", "glycan_involvement": "Glycosylation affects circulating levels.", "mechanism": "Benign cysts can cause mild elevation of CA-125 via peritoneal irritation.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "low", "disease": "Pelvic Inflammatory Disease", "glycan_involvement": "Glycosylation influences immune response.", "mechanism": "Inflammation of pelvic organs increases CA-125 release.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "low", "disease": "Uterine Leiomyoma", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "Leiomyomas may cause mild elevation of CA-125.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation in liver disease may affect CA-125 clearance.", "mechanism": "Liver dysfunction and ascites can increase CA-125.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "Glycosylation modulates immune interactions.", "mechanism": "Intestinal inflammation may elevate CA-125.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "high", "disease": "Peritoneal Tuberculosis", "glycan_involvement": "ADA is glycosylated, which may affect its stability and activity.", "mechanism": "Elevated ADA in ascitic fluid reflects T-cell activation in TB.", "protein": "Adenosine Deaminase (ADA)", "relationship_type": "biomarker", "source_pmcid": "PMC10923695" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated, which modulates immune evasion and receptor binding.", "mechanism": "Spike protein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", 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"G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC10923712" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity of spike protein.", "mechanism": "Used as antigen in recombinant vaccines (RCP) to elicit protective immunity.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10923712" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "RBD glycosylation influences antibody recognition.", "mechanism": "RBD is targeted by neutralizing antibodies induced by vaccination.", "protein": "Receptor Binding Domain (RBD) of Spike Protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC10923712" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgA is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Serum anti-RBD IgA levels correlate with vaccine-induced protection.", "protein": "IgA Antibody", "relationship_type": "biomarker", "source_pmcid": "PMC10923712" }, { "confidence": "low", "disease": "Myocarditis", "glycan_involvement": "Glycosylation may influence immunogenicity and off-target effects.", "mechanism": "Rare cases of myocarditis observed post-vaccination; possible immune response to spike protein.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal (rare adverse event)", "source_pmcid": "PMC10923712" }, { "confidence": "low", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "MS flare-ups reported post-vaccination; possible immune activation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal (rare adverse event)", "source_pmcid": "PMC10923712" }, { "confidence": "low", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may influence immune response.", "mechanism": "Psoriasis activation observed post-vaccination; possible immune modulation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal (rare adverse event)", "source_pmcid": "PMC10923712" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Glycosylation may affect mucosal immune response.", "mechanism": "Asthma attack observed post-intranasal vaccination; possible local immune activation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal (rare adverse event)", "source_pmcid": "PMC10923712" }, { "confidence": "low", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation may influence immune response.", "mechanism": "Crohn's disease activation observed post-vaccination; possible immune modulation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal (rare adverse event)", "source_pmcid": "PMC10923712" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein in vaccine formulation affects immunogenicity and efficacy.", "mechanism": "Vaccination with recombinant spike protein (RCP) provides protection against symptomatic COVID-19.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "protective", "source_pmcid": "PMC10923712" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "CRP is heavily glycosylated; glycosylation affects its stability and function.", "mechanism": "Elevated CRP is associated with worse cognitive performance and increased risk of incident dementia.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10925922" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "IL6 is glycosylated, which modulates its receptor binding and activity.", "mechanism": "Higher IL6 levels are associated with smaller brain volume and worse cognitive scores.", "protein": "Interleukin-6 (IL6)", "relationship_type": "biomarker", "source_pmcid": "PMC10925922" }, { "confidence": "low", "disease": "Cognitive decline", "glycan_involvement": "GlycA reflects N-acetyl glycan modifications on acute-phase proteins.", "mechanism": "GlycA is a composite marker of systemic inflammation; evidence for its association with cognition is mixed.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC10925922" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Platelet surface glycoproteins mediate interactions with neurogenic factors.", "mechanism": "Stable platelet counts may promote neurogenesis and protect against neurodegeneration.", "protein": "Platelet glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC10925922" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Monocyte glycoproteins facilitate migration and A\u03b2 uptake; glycosylation modulates these functions.", "mechanism": "Higher monocyte counts may enhance peripheral clearance of amyloid-beta, reducing AD pathology.", "protein": "Monocyte glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC10925922" }, { "confidence": "high", "disease": "Exceptional memory (EM)", "glycan_involvement": "Glycosylation affects monocyte trafficking and immune regulation.", "mechanism": "Higher baseline monocyte counts in EM families, especially men, may support cognitive resilience.", "protein": "Monocyte glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC10925922" }, { "confidence": "high", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation is essential for CRP's solubility and immune functions.", "mechanism": "CRP is a well-established marker of systemic inflammation and cardiovascular risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC10925922" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "IL6 glycosylation modulates its stability and signaling.", "mechanism": "Chronic elevation of IL6 is linked to metabolic dysfunction and diabetes risk.", "protein": "Interleukin-6 (IL6)", "relationship_type": "biomarker", "source_pmcid": "PMC10925922" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Platelet glycoproteins interact with neurotrophic factors; glycosylation affects these interactions.", "mechanism": "Reduced platelet count is associated with decreased neurogenesis in PD.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10925922" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates monocyte immune surveillance and tumor interactions.", "mechanism": "Chronic inflammation and altered monocyte function contribute to cancer risk.", "protein": "Monocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC10925922" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered N-glycosylation patterns (e.g., AFP-L3) increase specificity for HCC", "mechanism": "Elevated serum AFP levels indicate HCC presence", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Heparan sulfate glycosylation modulates signaling", "mechanism": "Overexpressed on HCC cells, involved in cell growth signaling", "protein": "Glypican-3 (GPC3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10928813" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects secretion and stability", "mechanism": "Abnormal DCP production in HCC due to defective carboxylation", "protein": "Des-gamma-carboxy prothrombin (DCP)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "O-glycosylation isomerization is detected by specific lectins", "mechanism": "Serum M2BPGi levels correlate with fibrosis stage", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates secretion and detection", "mechanism": "GP73 is upregulated in HCC and secreted into serum", "protein": "Golgi protein 73 (GP73)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "medium", "disease": "Chronic hepatitis", "glycan_involvement": "Glycoform patterns differ from HCC", "mechanism": "Mildly elevated AFP can indicate chronic liver inflammation", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "medium", "disease": "Chronic hepatitis", "glycan_involvement": "O-glycosylation changes reflect disease progression", "mechanism": "M2BPGi levels increase with progression to fibrosis", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC10928813" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated IL-6 in liver and colon tissue correlates with NAFLD severity and inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 mediates steatosis, inflammation, and fibrosis in NAFLD.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates receptor binding and stability.", "mechanism": "TNF-\u03b1 levels are elevated in NAFLD and correlate with disease severity.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation required for chemokine function.", "mechanism": "MCP-1 is increased in liver and colon in NAFLD, indicating inflammation.", "protein": "MCP-1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect activation and localization.", "mechanism": "Altered expression in NAFLD liver tissue; involved in apoptosis.", "protein": "Caspase-8", "protein_enriched": { "function": "Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic devel", "gene_name": "CASP8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14790" }, "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Potential glycosylation affects protein stability.", "mechanism": "Keap-1/Nrf2 pathway modulates oxidative stress in NAFLD.", "protein": "Keap-1", "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may regulate nuclear translocation.", "mechanism": "Nrf2 activation protects against oxidative damage in NAFLD.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC10929648" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "OH-1 expression is protective against liver injury in NAFLD.", "protein": "OH-1 (Heme oxygenase-1)", "relationship_type": "protective", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation required for enzyme stability.", "mechanism": "Elevated ALT is a sensitive indicator of hepatocellular injury in NAFLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation required for enzyme stability.", "mechanism": "Elevated AST reflects liver injury and progression of NAFLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC10929648" }, { "confidence": "high", "disease": "AECOPD", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP predicts increased risk of corticosteroid treatment failure in AECOPD, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "AECOPD", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion and immune signaling; glycosylation modulates function.", "mechanism": "Low platelet count predicts corticosteroid treatment failure, possibly due to impaired immune and inflammatory responses.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "AECOPD", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB); glycosylation affects receptor binding and clearance.", "mechanism": "Low LDL-C levels are associated with increased risk of treatment failure, possibly reflecting severe infection/inflammation.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "Malnutrition/immune deficiency", "glycan_involvement": "Albumin is glycosylated; glycosylation influences half-life and immune modulation.", "mechanism": "Low albumin (part of PNI) indicates poor nutritional/immune status, predicting poor corticosteroid response.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "Malnutrition/immune deficiency", "glycan_involvement": "Transthyretin is glycosylated; glycan structures affect stability and transport.", "mechanism": "Low prealbumin (PALB) is linked to poor nutritional status and immune function, affecting corticosteroid outcomes.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells and complement.", "mechanism": "Elevated CRP is associated with increased risk of ischemic heart disease and poor outcomes in AECOPD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "Chronic hepatic disease", "glycan_involvement": "CRP glycosylation may be altered in liver disease, affecting function.", "mechanism": "High CRP and chronic hepatic disease together predict poor corticosteroid response in AECOPD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "high", "disease": "AECOPD", "glycan_involvement": "Eosinophil surface glycoproteins mediate cell-cell interactions; glycosylation affects migration and activation.", "mechanism": "Low eosinophil count predicts corticosteroid treatment failure, especially in smokers; reflects inflammatory phenotype.", "protein": "Eosinophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "AECOPD", "glycan_involvement": "Glycosylation status may influence albumin's anti-inflammatory properties.", "mechanism": "Low albumin (as part of PNI) predicts poor corticosteroid response in AECOPD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation of platelet glycoproteins modulates aggregation and immune signaling.", "mechanism": "Platelet count and function (via glycoproteins) are linked to cardiovascular risk and outcomes in AECOPD.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC10929658" }, { "confidence": "high", "disease": "Bacterial infection", "glycan_involvement": "TRAIL is a glycoprotein; glycosylation may affect its stability and detection.", "mechanism": "TRAIL levels are integrated in the MeMed BV\u00ae score to differentiate bacterial from viral infections.", "protein": "TRAIL", "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "high", "disease": "Viral infection", "glycan_involvement": "IP-10 is glycosylated, which may influence its secretion and function.", "mechanism": "IP-10 is part of the MeMed BV\u00ae score, elevated in viral infections.", "protein": "IP-10 (CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "high", "disease": "Bacterial infection", "glycan_involvement": "CRP glycosylation affects its immunological activity and clearance.", "mechanism": "CRP is included in the MeMed BV\u00ae score, typically elevated in bacterial infections.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "high", "disease": "Intestinal injury", "glycan_involvement": "IFABP is glycosylated; glycosylation may affect its release and detection.", "mechanism": "Plasma IFABP is a marker of intestinal injury after cardiac arrest.", "protein": "Intestinal fatty acid binding protein (IFABP)", "protein_enriched": { "function": "FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds satura", "gene_name": "FABP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12104" }, "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "medium", "disease": "Multiple organ dysfunction", "glycan_involvement": "Glycosylation may modulate IFABP's stability and inflammatory signaling.", "mechanism": "Higher IFABP is associated with increased SOFA score and mortality, partially mediated by IL-6.", "protein": "Intestinal fatty acid binding protein (IFABP)", "protein_enriched": { "function": "FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds satura", "gene_name": "FABP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12104" }, "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "medium", "disease": "Vascular leakage", "glycan_involvement": "P-protein is a glycoprotein; glycosylation likely affects its therapeutic potential.", "mechanism": "Higher plasma P-protein levels are associated with reduced vascular leakage and improved survival post-cardiac arrest.", "protein": "P-protein", "relationship_type": "protective", "source_pmcid": "PMC10949559" }, { "confidence": "medium", "disease": "Post-cardiac arrest syndrome", "glycan_involvement": "Glycosylation may be critical for P-protein's bioactivity and stability.", "mechanism": "Recombinant P-protein administration reduces vascular leakage and improves cardiac function after resuscitation.", "protein": "P-protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC10949559" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP glycosylation modulates its immunological properties.", "mechanism": "CRP is used in sepsis diagnostics and is elevated in systemic inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect TRAIL's apoptotic signaling in sepsis.", "mechanism": "TRAIL is part of the MeMed BV\u00ae score for sepsis diagnosis.", "protein": "TRAIL", "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may influence IP-10's chemotactic activity in sepsis.", "mechanism": "IP-10 is included in the MeMed BV\u00ae score for sepsis diagnosis.", "protein": "IP-10 (CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC10949559" }, { "confidence": "high", "disease": "Type II Diabetes Mellitus", "glycan_involvement": "GLP-1 agonists are glycoproteins; glycosylation affects their stability and receptor binding.", "mechanism": "GLP-1 agonists improve metabolic health and glycemic control, promote weight loss, and may reduce insulin requirements.", "protein": "GLP-1 receptor agonists (Liraglutide, Exenatide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11035192" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation enhances pharmacokinetics and bioactivity.", "mechanism": "GLP-1 agonists promote weight loss, reducing obesity risk in pediatric diabetics.", "protein": "GLP-1 receptor agonists (Liraglutide, Exenatide)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11035192" }, { "confidence": "high", "disease": "Type II Diabetes Mellitus", "glycan_involvement": "Insulin is glycosylated, which affects its stability and activity.", "mechanism": "Insulin therapy is used to control blood glucose but may lead to weight gain.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11035192" }, { "confidence": "high", "disease": "Type II Diabetes Mellitus", "glycan_involvement": "A1C is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "A1C is a marker of long-term glycemic control.", "protein": "Hemoglobin A1C", "relationship_type": "biomarker", "source_pmcid": "PMC11035192" }, { "confidence": "medium", "disease": "Type II Diabetes Mellitus", "glycan_involvement": "Glycosylation is essential for drug efficacy and half-life.", "mechanism": "GLP-1 agonists may slow diabetes complications by improving metabolic health and reducing weight.", "protein": "GLP-1 receptor agonists (Liraglutide, Exenatide)", "relationship_type": "protective", "source_pmcid": "PMC11035192" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects insulin's pharmacodynamics.", "mechanism": "Insulin use can lead to weight gain in pediatric diabetics.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11035192" }, { "confidence": "medium", "disease": "vasculitis", "glycan_involvement": "Beta-2 glycoprotein I is a plasma glycoprotein with N-glycosylation important for its function and antigenicity.", "mechanism": "Anti-beta-2 glycoprotein antibodies are commonly screened as biomarkers for autoimmune-mediated vasculitis.", "protein": "anti-beta-2 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11046660" }, { "confidence": "medium", "disease": "Peripheral precocious puberty", "glycan_involvement": "Estradiol is a glycoprotein hormone; glycosylation affects stability and receptor interaction.", "mechanism": "Elevated estradiol is associated with gonadotropin suppression and peripheral precocious puberty.", "protein": "Estradiol", "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "GGT is glycosylated, which affects its secretion and activity.", "mechanism": "Elevated GGT indicates liver dysfunction.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Serum proteins are often glycosylated, affecting their function and clearance.", "mechanism": "Abnormal serum protein levels can indicate liver disease.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Albumin glycosylation affects its half-life and function.", "mechanism": "Low albumin is a marker of liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Hemolytic anemia", "glycan_involvement": "Minor glycosylation affects hemoglobin stability.", "mechanism": "Hemolytic anemia leads to abnormal hemoglobin levels.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Urticaria", "glycan_involvement": "Glycosylation modulates immunoglobulin effector functions.", "mechanism": "Immune response mediated by immunoglobulins can cause urticaria.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Liver disease", "glycan_involvement": "LDL glycosylation affects receptor binding and clearance.", "mechanism": "Altered LDL levels can indicate liver dysfunction.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Liver disease", "glycan_involvement": "HDL glycosylation affects its anti-inflammatory properties.", "mechanism": "Altered HDL levels can indicate liver dysfunction.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Bone development", "glycan_involvement": "Bioactive glycoproteins require glycosylation for activity.", "mechanism": "Deer antler glycoproteins may promote bone formation gene expression.", "protein": "Deer antler glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11062680" }, { "confidence": "low", "disease": "Proteinuria", "glycan_involvement": "Glycosylation affects albumin filtration and renal handling.", "mechanism": "Albumin in urine is a marker of proteinuria and renal disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062680" }, { "confidence": "high", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "N-glycosylation affects CD36 trafficking and function.", "mechanism": "Upregulated in SIM muscle; involved in fatty acid transport and oxidative stress response.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062695" }, { "confidence": "high", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Downregulated in SIM; key ROS scavenger, regulates oxidative stress in muscle.", "protein": "GPX3", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione", "gene_name": "GPX3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22352" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Differentially expressed in SIM; detoxifies quinones, supports antioxidant defense.", "protein": "NQO1", "protein_enriched": { "function": "Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons ar", "gene_name": "NQO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15559" }, "relationship_type": "biomarker", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Differentially expressed in SIM; maintains glutathione pool, regulates mitochondrial ROS.", "protein": "GSR", "relationship_type": "biomarker", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Upregulated in SIM; regulates antioxidant genes and apoptosis in response to oxidative stress.", "protein": "TP53", "relationship_type": "biomarker", "source_pmcid": "PMC11062695" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor function.", "mechanism": "CD36 variants increase susceptibility to cardiovascular disease via altered lipid metabolism and inflammation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation affects cell surface expression.", "mechanism": "CD36 polymorphisms linked to metabolic syndrome and diabetes risk.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for extracellular antioxidant activity.", "mechanism": "GPX3 acts as a tumor suppressor by reducing ROS and limiting DNA damage.", "protein": "GPX3", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione", "gene_name": "GPX3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22352" }, "relationship_type": "protective", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "N-glycosylation essential for ligand recognition and cell adhesion.", "mechanism": "Endothelial injury and E-selectin-mediated leukocyte adhesion contribute to SIM pathogenesis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC11062695" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation modulates receptor-ligand interactions.", "mechanism": "Oxidized LDL/CD36 signaling links fatty acid metabolism to mitochondrial oxidative stress and inflammation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11062695" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Part of system xc- antiporter; inhibition induces ferroptosis in cancer cells.", "protein": "SLC3A2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11067110" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation affects stability and transport activity.", "mechanism": "System xc- light chain; inhibition (e.g., by erastin) induces ferroptosis, especially in RAS-mutant cancers.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11067110" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates receptor binding and iron delivery.", "mechanism": "Delivers iron for Fenton reaction, promoting lipid peroxidation and ferroptosis.", "protein": "Transferrin (TF)", "relationship_type": "causal", "source_pmcid": "PMC11067110" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "Mediates iron uptake, increasing ferroptosis sensitivity in tumor cells.", "protein": "Transferrin receptor (TFRC)", "relationship_type": "causal", "source_pmcid": "PMC11067110" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation regulates enzymatic activity and membrane localization.", "mechanism": "Forms complex with NOX1, promoting ROS and ferroptosis in TP53-deficient colorectal cancer.", "protein": "DPP4", "relationship_type": "causal", "source_pmcid": "PMC11067110" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation status not specified; presumed for protein stability.", "mechanism": "Promotes KEAP1 degradation, stabilizing NFE2L2 and conferring resistance to ferroptosis.", "protein": "SQSTM1", "relationship_type": "protective", "source_pmcid": "PMC11067110" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect metal binding and stability.", "mechanism": "Binds metal ions, reducing iron-mediated oxidative stress and ferroptosis.", "protein": "Metallothionein 1G (MT1G)", "protein_enriched": { "function": "Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids", "gene_name": "MT1G", "glycan_count": 10, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G07246CJ", "G35253PZ", "G39446WN", "G40834TG", "G41840AI", "G59324HL", "G65000LJ", "G77669RF", "G90787TS", "G92135MA" ], "uniprot_id": "P13640" }, "relationship_type": "protective", "source_pmcid": "PMC11067110" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for ER localization and function.", "mechanism": "ER-resident glycoprotein; inhibits ferroptosis via antioxidant activity, upregulated in leukemia.", "protein": "TXNDC12", "protein_enriched": { "function": "Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates (PubMed:16940051, PubMed:23192347). Binds protein substrates via a hydrophobic pocket in t", "gene_name": "ERP27", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q96DN0" }, "relationship_type": "protective", "source_pmcid": "PMC11067110" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "N-glycosylation affects drug sensitivity.", "mechanism": "Targeted by sulfasalazine, reducing cystine uptake and GSH synthesis.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11067110" }, { "confidence": "high", "disease": "Sedaghatian-type spinal metaphyseal dysplasia", "glycan_involvement": "Not glycosylated.", "mechanism": "R152H mutation disrupts allosteric activation, causing disease.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC11067110" }, { "confidence": "high", "disease": "Hypoxemia after acute type A aortic dissection surgery", "glycan_involvement": "UTI is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "UTI upregulates tight junction proteins, Na-K-ATPase, and ENaC, reducing alveolar permeability and improving oxygenation.", "protein": "Ulinastatin (UTI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Hypoxemia after acute type A aortic dissection surgery", "glycan_involvement": "Glycosylation modulates leukocyte adhesion and migration.", "mechanism": "Leukocyte count reflects systemic inflammatory response, which is associated with postoperative hypoxemia.", "protein": "Leukocyte cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Transfusion-related acute lung injury (TRALI)", "glycan_involvement": "Endothelial glycoprotein glycosylation affects neutrophil binding and vascular permeability.", "mechanism": "Activated neutrophils interact with endothelial glycoproteins, causing endothelial damage and pulmonary edema.", "protein": "Endothelial cell adhesion glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "ENaC glycosylation is required for membrane localization and function.", "mechanism": "Upregulation of ENaC enhances alveolar fluid clearance, reducing pulmonary edema.", "protein": "ENaC (Epithelial sodium channel)", "relationship_type": "protective", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation is necessary for Na-K-ATPase stability and trafficking.", "mechanism": "Increased Na-K-ATPase activity promotes alveolar fluid clearance.", "protein": "Na-K-ATPase", "relationship_type": "protective", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation of TJ proteins regulates barrier integrity.", "mechanism": "Upregulation of TJ proteins decreases alveolar permeability, limiting edema.", "protein": "Tight Junction (TJ) proteins", "relationship_type": "protective", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates leukocyte-endothelial interactions.", "mechanism": "Leukocyte-mediated inflammation damages alveolar-capillary barrier, leading to ARDS.", "protein": "Leukocyte cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation status affects endothelial barrier function.", "mechanism": "Endothelial activation and injury increase vascular permeability and lung edema.", "protein": "Endothelial cell adhesion glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation is essential for UTI's anti-inflammatory activity.", "mechanism": "UTI reduces inflammation and improves alveolar fluid clearance.", "protein": "Ulinastatin (UTI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11067146" }, { "confidence": "medium", "disease": "Hypoxemia after acute type A aortic dissection surgery", "glycan_involvement": "Glycosylation modulates TJ protein function and localization.", "mechanism": "TJ protein upregulation improves alveolar barrier, reducing hypoxemia.", "protein": "Tight Junction (TJ) proteins", "relationship_type": "protective", "source_pmcid": "PMC11067146" }, { "confidence": "high", "disease": "Crop lactation deficiency", "glycan_involvement": "PRL is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "PRL regulates crop milk production by promoting protein and lipid synthesis in crop tissue.", "protein": "Prolactin (PRL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11068619" }, { "confidence": "high", "disease": "Crop lactation deficiency", "glycan_involvement": "VIP is not glycosylated but regulates glycoprotein hormone release.", "mechanism": "VIP acts as prolactin-releasing factor, stimulating PRL secretion via cAMP pathway.", "protein": "Vasoactive Intestinal Peptide (VIP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11068619" }, { "confidence": "medium", "disease": "Abnormal crop epithelial proliferation", "glycan_involvement": "PGF is glycosylated; glycosylation modulates its angiogenic activity.", "mechanism": "PGF promotes blood vessel development and epithelial proliferation in crop tissue.", "protein": "Placental Growth Factor (PGF)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11068619" }, { "confidence": "medium", "disease": "Crop lactation deficiency", "glycan_involvement": "FSHB is glycosylated; glycosylation is essential for hormone bioactivity.", "mechanism": "FSHB expression changes may indicate pituitary endocrine status affecting lactation.", "protein": "Follicle Stimulating Hormone subunit beta (FSHB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "medium", "disease": "Crop lactation deficiency", "glycan_involvement": "CGA is N-glycosylated; glycosylation required for secretion and function.", "mechanism": "CGA is a common subunit for several pituitary glycoprotein hormones; altered expression may affect hormone signaling.", "protein": "Glycoprotein hormones, alpha polypeptide (CGA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "medium", "disease": "Abnormal crop epithelial proliferation", "glycan_involvement": "EGF is glycosylated; glycosylation affects receptor interaction.", "mechanism": "EGF stimulates epithelial cell proliferation in crop tissue.", "protein": "Epidermal Growth Factor (EGF)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11068619" }, { "confidence": "low", "disease": "Impaired nurturing behavior", "glycan_involvement": "POMC is glycosylated; glycosylation influences peptide processing.", "mechanism": "POMC-derived peptides may modulate behavior relevant to nurturing.", "protein": "Proopiomelanocortin (POMC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "low", "disease": "Impaired nurturing behavior", "glycan_involvement": "NPY is not glycosylated.", "mechanism": "NPY regulates feeding and nurturing behaviors.", "protein": "Neuropeptide Y (NPY)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "low", "disease": "Abnormal crop epithelial proliferation", "glycan_involvement": "AGT is glycosylated; glycosylation affects secretion and activity.", "mechanism": "AGT may influence vascular development in crop tissue.", "protein": "Angiotensinogen (AGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "low", "disease": "Impaired nurturing behavior", "glycan_involvement": "GRP is not glycosylated.", "mechanism": "GRP may modulate neuroendocrine signaling relevant to nurturing.", "protein": "Gastrin-releasing peptide (GRP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11068619" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "LAMP1 is a heavily N-glycosylated lysosomal membrane protein; glycosylation is essential for its stability and function.", "mechanism": "LAMP1 abundance increases in microglia after exposure to PD plasma exosomes, indicating lysosomal accumulation and dysfunction.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "LAMP2 is N-glycosylated; glycosylation is required for lysosomal targeting and function.", "mechanism": "LAMP2 levels increase in microglia after PD-exo treatment; LAMP2 degradation is linked to increased exosomal \u03b1-syn secretion.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11069054" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Cathepsin D is N-glycosylated; glycosylation is required for lysosomal trafficking and enzymatic activity.", "mechanism": "Cathepsin D activity decreases in microglia after PD-exo or V1G1 knockdown, impairing \u03b1-syn degradation.", "protein": "Cathepsin D", "relationship_type": "causal", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Cathepsin B is N-glycosylated; glycosylation is important for lysosomal localization.", "mechanism": "Cathepsin B mRNA is measured as a lysosomal hydrolase; its dysfunction is implicated in impaired protein degradation in PD.", "protein": "Cathepsin B", "relationship_type": "causal", "source_pmcid": "PMC11069054" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "No direct evidence of glycosylation, but as a lysosomal membrane protein, potential glycosylation may affect stability/function.", "mechanism": "Downregulation of V1G1 by PD-exo impairs lysosomal acidification, leading to \u03b1-syn accumulation and neuroinflammation; V1G1 overexpression is neuroprotective.", "protein": "ATP6V1G1 (V1G1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11069054" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Not glycosylated.", "mechanism": "Pathogenic \u03b1-syn oligomers accumulate in exosomes from PD patients, propagate in microglia, and induce neuroinflammation.", "protein": "Alpha-synuclein (\u03b1-syn)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Lysosomal storage diseases", "glycan_involvement": "N-glycosylation is essential for LAMP1 function.", "mechanism": "LAMP1 is a general marker of lysosomal abundance and dysfunction in lysosomal storage diseases.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). 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"G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", 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"G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Cathepsin D dysfunction is associated with impaired degradation of protein aggregates in AD.", "protein": "Cathepsin D", "relationship_type": "causal", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Lysosomal storage diseases", "glycan_involvement": "Potential glycosylation may affect function.", "mechanism": "V-ATPase dysfunction, including V1G1, is implicated in lysosomal storage diseases due to impaired acidification.", "protein": "ATP6V1G1 (V1G1)", "relationship_type": "causal", "source_pmcid": "PMC11069054" }, { "confidence": "medium", "disease": "Juvenile-onset familial Parkinson's disease", "glycan_involvement": "N-glycosylation required for lysosomal targeting.", "mechanism": "LAMP2 degradation via ubiquitin-proteasome system increases exosomal \u03b1-syn secretion, contributing to familial PD.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", 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"G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "causal", "source_pmcid": "PMC11069054" }, { "confidence": "high", "disease": "Severe malnutrition", "glycan_involvement": "N-glycosylation affects albumin stability and half-life; hypoalbuminemia may reflect altered glycosylation.", "mechanism": "Low albumin reflects impaired hepatic protein synthesis due to liver autophagy and dysfunction in severe malnutrition.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "high", "disease": "Severe malnutrition", "glycan_involvement": "N-glycosylation modulates prealbumin secretion and stability.", "mechanism": "Low prealbumin indicates acute protein-energy malnutrition and hepatic synthetic failure.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "high", "disease": "Liver failure", "glycan_involvement": "N-glycosylation required for secretion and activity; altered in liver dysfunction.", "mechanism": "Decreased cholinesterase reflects reduced hepatic synthetic function in end-stage malnutrition.", "protein": "Cholinesterase (Butyrylcholinesterase)", "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "high", "disease": "Liver failure", "glycan_involvement": "N-glycosylation essential for secretion and function of prothrombin.", "mechanism": "Low prothrombin time indicates impaired hepatic synthesis of coagulation factors.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation required for thrombopoietin secretion and activity.", "mechanism": "Reduced hepatic production of thrombopoietin leads to low platelet counts in severe malnutrition.", "protein": "Thrombopoietin", "protein_enriched": { "function": "Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:11741539, PubMed:9230079). The Arp2/3 complex m", "gene_name": "ARPC1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15143" }, "relationship_type": "causal", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Severe malnutrition", "glycan_involvement": "N-glycosylation affects transferrin stability and iron binding.", "mechanism": "Low transferrin reflects impaired hepatic protein synthesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "CRP is an acute phase reactant; levels may be blunted in severe malnutrition due to hepatic dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Severe malnutrition", "glycan_involvement": "N-glycosylation critical for immunoglobulin function.", "mechanism": "Low lymphocyte count reflects impaired immune glycoprotein production due to liver dysfunction.", "protein": "Total lymphocyte count (immunoglobulins)", "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated AST indicates hepatocellular injury in severe malnutrition.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT reflects hepatocellular injury and autophagy in end-stage malnutrition.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069231" }, { "confidence": "high", "disease": "Tumor metastasis", "glycan_involvement": "Glycosylation modulates HA binding and cell motility.", "mechanism": "CD44 binds hyaluronan, facilitating cell migration and metastasis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Wound repair", "glycan_involvement": "Glycosylation affects receptor-ligand interactions.", "mechanism": "CD105+ MSCs promote angiogenesis and tissue regeneration.", "protein": "CD105 (Endoglin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11069290" }, { "confidence": "high", "disease": "Immune dysregulation", "glycan_involvement": "Binds \u03b2-galactoside glycans on immune cells.", "mechanism": "Galectin-1 suppresses T-cell proliferation, modulating immune response.", "protein": "Galectin-1 (LGALS1)", "relationship_type": "protective", "source_pmcid": "PMC11069290" }, { "confidence": "high", "disease": "Inflammatory disease", "glycan_involvement": "N-glycosylation regulates ICAM1 function.", "mechanism": "ICAM1 mediates leukocyte adhesion and transmigration in inflammation.", "protein": "ICAM1", "relationship_type": "causal", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Cartilage degeneration", "glycan_involvement": "Glycosylation modulates integrin activation.", "mechanism": "ITGB1 mediates cell-ECM interactions critical for cartilage integrity.", "protein": "Integrin beta-1 (ITGB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Osteogenesis imperfecta", "glycan_involvement": "Glycosylation affects collagen assembly.", "mechanism": "COL6A3 mutations disrupt ECM, leading to bone fragility.", "protein": "COL6A3", "protein_enriched": { "function": "Structural component of hyaline cartilage and vitreous of the eye", "gene_name": "COL9A2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14055" }, "relationship_type": "causal", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Glycosylation influences cell adhesion properties.", "mechanism": "CD166 expression correlates with metastatic potential.", "protein": "CD166 (ALCAM)", "protein_enriched": { "function": "Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:15048703, PubMed:15496415, PubMed:16352806, PubMe", "gene_name": "ALCAM", "glycan_count": 163, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G02815KT", "G04657PL", "G05049YU", "G06110VR", "G06356OH", "G07755XJ", "G08918WF", "G10486CT", "G14972EH", "G17208MA", "G20210JR", "G23863VK", "G25451PN", "G27058EU", "G27126ED", "G34989PA", "G37412TK", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G46503DX", "G46691LC", "G47012YE", "G48414YA", "G49018RC", "G50045TK", "G58954YZ", "G59626AS", "G60033FS", "G60177UT", "G60923RB", "G65184UU", "G70101JE", "G70619PT", "G72790NZ", "G75983OB", "G76295SF", "G79666IR", "G80223IX", "G83229XP", "G83646BJ", "G84452RH", "G84820NF", "G86182NS", "G87051GH", "G87661QW", "G90659AW", "G90734RJ", "G92062TF", "G95133RI", "G95177YH", "G95865ZB", "G01160VV", "G05962QB", "G06247RL", "G07246CJ", "G10819WX", "G11115RO", "G13131HA", "G16125XL", "G18183SM", "G22589VJ", "G27915IV", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G34617SM", "G35541EV", "G38663NM", "G43089EG", "G50427EO", "G52890YB", "G53075ES", "G55132BD", "G57776ZS", "G62765YT", "G64394MX", "G68490OW", "G70232NH", "G70441OD", "G70894RY", "G72797UR", "G79286RS", "G80479JV", "G80920RR", "G81263BG", "G85282JO", "G85554PZ", "G87123QX", "G90093AU", "G90382BL", "G92135MA", "G93718GY", "G96577RX", "G98611JV", "G02030ZB", "G11629QQ", "G11870QZ", "G20312EM", "G25418HZ", "G31544HA", "G33791AF", "G43734MM", "G47644PP", "G51640FO", "G64527OM", "G66163OV", "G69521XL", "G77547TA", "G77582RK", "G80075MS", "G82830MN", "G84225JN", "G86795LJ", "G05933EN", "G08290VR", "G15169WU", "G18647XP", "G23294PN", "G37881RL", "G40834TG", "G47518TP", "G63041LO", "G66760KM", "G78649WQ", "G96430BV", "G02852RP", "G00273SJ", "G05724UK", "G10773YW", "G10846ZT", "G12313PD", "G13749ZZ", "G14260UH", "G23984SE", "G31852PQ", "G37399XV", "G39188ZX", "G40926MX", "G41126SR", "G41840AI", "G44753VC", "G49906RN", "G50372IH", "G62894KT", "G70418MS", "G72291OX", "G72735IY", "G82463GQ", "G86880BF", "G54992WG", "G65414LI", "G83676GD", "G52527GH", "G63381RX", "G70822IO", "G49108TO" ], "uniprot_id": "Q13740" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Graft-versus-host disease", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "CD200 suppresses immune activation, reducing GVHD risk.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "protective", "source_pmcid": "PMC11069290" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects enzymatic activity.", "mechanism": "CD73 regulates adenosine production, modulating vascular inflammation.", "protein": "CD73 (NT5E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11069290" }, { "confidence": "low", "disease": "Neurodegeneration", "glycan_involvement": "Glycosylation influences cell-cell interactions.", "mechanism": "CD90 marks neuronal and stromal cells involved in neurodegenerative processes.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "biomarker", "source_pmcid": "PMC11069290" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "TNF\u03b1 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "Increased TNF\u03b1 expression promotes inflammation and liver injury in response to alcohol.", "protein": "TNF\u03b1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11075036" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "IL-6 glycosylation modulates its receptor binding and activity.", "mechanism": "IL-6 upregulation is associated with inflammation and progression of liver damage.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11075036" }, { "confidence": "medium", "disease": "Alcoholic liver disease", "glycan_involvement": "TLR4 N-glycosylation is essential for its cell surface expression and function.", "mechanism": "Alcohol and dietary fats upregulate TLR4, increasing sensitivity to endotoxin and promoting inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC11075036" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "TGF-\u03b2 glycosylation regulates its secretion and bioactivity.", "mechanism": "TGF-\u03b2 promotes activation of hepatic stellate cells and fibrogenesis.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11075036" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "HBsAg is heavily glycosylated; glycosylation affects immune evasion and pathogenicity.", "mechanism": "HBV infection (HBsAg) synergizes with alcohol to promote HCC.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11075036" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "HCV core protein glycosylation modulates immune recognition.", "mechanism": "HCV core protein and alcohol synergistically increase oxidative stress and fibrosis.", "protein": "Hepatitis C virus core protein", "relationship_type": "causal", "source_pmcid": "PMC11075036" }, { "confidence": "low", "disease": "Steatosis (fatty liver)", "glycan_involvement": "HDL-associated glycoproteins' glycosylation affects lipid transport.", "mechanism": "Alcohol and high-fat diet increase HDL and liver steatosis.", "protein": "HDL (contains glycoproteins such as ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC11075036" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "ALT elevation indicates hepatocyte injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11075036" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "AST elevation indicates hepatocyte injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11075036" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "CYP2E1 induction by alcohol increases oxidative stress and liver injury.", "protein": "CYP2E1", "relationship_type": "causal", "source_pmcid": "PMC11075036" }, { "confidence": "medium", "disease": "Innate and adaptive immune response", "glycan_involvement": "MFGE8 is a glycoprotein; glycosylation may affect binding affinity.", "mechanism": "MFGE8 bridges phosphatidylserine on EVs to integrins on antigen-presenting cells, facilitating immune cell interactions.", "protein": "MFGE8", "relationship_type": "causal", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IgG glycosylation modulates immune complex formation and effector function.", "mechanism": "IgG binds to autoantigen-coated EVs, forming immune complexes that drive inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Fibrinogen is glycosylated; glycan structures may influence immune recognition.", "mechanism": "Fibrinogen adsorbs onto platelet-derived EVs, serving as autoantigen for immune complex formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "General inflammation", "glycan_involvement": "CRP is glycosylated; glycosylation may affect its binding and function.", "mechanism": "CRP binds to EVs, undergoes conformational change, activates complement, and promotes inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Tissue factor is glycosylated; glycosylation may modulate activity.", "mechanism": "Tissue factor on EVs initiates coagulation cascade, promoting thrombosis.", "protein": "Tissue factor", "relationship_type": "causal", "source_pmcid": "PMC11080634" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Fibronectin is heavily glycosylated; glycans mediate interactions with heparan sulfate proteoglycans.", "mechanism": "Fibronectin bridges EVs and target cells via integrins/heparan sulfate, promoting adhesion and metastasis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC11080634" }, { "confidence": "medium", "disease": "Immune complex diseases", "glycan_involvement": "C1q is glycosylated; glycosylation may affect immune recognition.", "mechanism": "C1q binds to EVs (via surface proteins/lipids), activates classical complement pathway.", "protein": "Complement C1q", "relationship_type": "causal", "source_pmcid": "PMC11080634" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "C3 is glycosylated; glycosylation may influence complement activation.", "mechanism": "C3 fragments deposit on EVs, contributing to immune complex formation and inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation is critical for spike binding and EV function.", "mechanism": "ACE2-enriched EVs bind SARS-CoV-2 spike protein, blocking viral entry into host cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Tissue factor glycosylation may affect procoagulant activity.", "mechanism": "Tissue factor-enriched EVs in plasma correlate with COVID-19 severity and promote coagulopathy.", "protein": "Tissue factor", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11080634" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CagA is glycosylated, which may affect its stability and interaction with host cells.", "mechanism": "Exosome-mediated transfer of CagA from H. pylori-infected gastric cells to endothelial cells increases ROS and inflammation, impairing endothelial function and promoting atherosclerosis.", "protein": "Cytotoxin-associated gene A (CagA)", "relationship_type": "causal", "source_pmcid": "PMC11080793" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "ICAM-1 is heavily N-glycosylated, influencing cell-cell interactions.", "mechanism": "Upregulated in endothelial cells in response to infection and exosomal miRNAs, promoting leukocyte adhesion and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC11080793" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "VCAM-1 glycosylation modulates its adhesive properties.", "mechanism": "Exosomal miR-25 from H. pylori-infected cells upregulates VCAM-1, increasing vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC11080793" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "vWF is highly glycosylated, affecting its multimerization and function.", "mechanism": "Elevated vWF in sepsis reflects endothelial activation and dysfunction.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11080793" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "MHC-II glycosylation affects antigen presentation.", "mechanism": "Exosomes carrying MHC-II and mycobacterial antigens activate T cells, promoting protective immunity.", "protein": "MHC-II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11080793" }, { "confidence": "high", "disease": "Cryptococcal meningoencephalitis", "glycan_involvement": "GXM is a polysaccharide with glycan epitopes critical for immune evasion.", "mechanism": "Fungal EVs containing GXM modulate the extracellular environment and facilitate blood-brain barrier traversal.", "protein": "Glucuronoxylomannan (GXM)", "relationship_type": "causal", "source_pmcid": "PMC11080793" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Tetraspanins are glycosylated, influencing exosome targeting and uptake.", "mechanism": "Exosomal tetraspanins facilitate SARS-CoV-2 entry and dissemination.", "protein": "Tetraspanins (CD9, CD63, CD81)", "relationship_type": "causal", "source_pmcid": "PMC11080793" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "gp63 glycosylation modulates its protease activity and immune interactions.", "mechanism": "EVs carrying gp63 degrade immune receptors, impairing host immune response.", "protein": "gp63 (Leishmania surface glycoprotein)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8I7T7" }, "relationship_type": "causal", "source_pmcid": "PMC11080793" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "OMV-derived \u03b2-lactamase hydrolyzes antibiotics, protecting bacteria and worsening infection.", "protein": "\u03b2-lactamase", "relationship_type": "causal", "source_pmcid": "PMC11080793" }, { "confidence": "low", "disease": "Endothelial dysfunction", "glycan_involvement": "HSP70 glycosylation may influence its chaperone activity and exosomal sorting.", "mechanism": "Exosomal HSP70 is upregulated during infection and stress, modulating immune responses.", "protein": "Heat shock protein 70 (HSP70)", "relationship_type": "biomarker", "source_pmcid": "PMC11080793" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "O-glycosylation required for P-selectin binding.", "mechanism": "PSGL-1 on monocytic/macrophage-derived EVs binds P-selectin on platelets/PEVs, facilitating coagulation.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "Cancer (gastric, colon)", "glycan_involvement": "N-glycosylation affects stability and localization.", "mechanism": "CD39 on B cell-derived EVs hydrolyzes ATP to adenosine, suppressing T cell activation and promoting immunosuppressive tumor microenvironment.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "Cancer (gastric, colon)", "glycan_involvement": "N-glycosylation modulates enzymatic activity.", "mechanism": "CD73 on B cell-derived EVs converts AMP to adenosine, contributing to immunosuppression and poor prognosis.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11080875" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation regulates ligand binding.", "mechanism": "Integrins on B cell-derived EVs mediate adhesion to ECM and activated fibroblasts, triggering inflammatory signaling.", "protein": "Integrin \u03b21/\u03b14", "relationship_type": "causal", "source_pmcid": "PMC11080875" }, { "confidence": "medium", "disease": "Vascular injury", "glycan_involvement": "O- and N-glycosylation modulate immune recognition.", "mechanism": "GPA on RBCEVs marks RBC origin and may participate in vascular interactions.", "protein": "Glycophorin A (GPA)", "protein_enriched": { "function": "Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Glycophorin A is the major intrinsic membrane protein of t", "gene_name": "GYPA", "glycan_count": 28, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G16370GQ", "G33350UC", "G42797SX", "G47180UC", "G56245IE", "G56682BC", "G65562ZE", "G94217FB", "G94435QH", "G29931IJ", "G49108TO", "G81006GJ", "G57321FI", "G29068FM", "G43417UB", "G02030ZB", "G09480OP", "G14127XU", "G19399OS", "G31916IQ", "G32948PW", "G33947BV", "G74722FL", "G76163CP", "G85608AG", "G91473PK" ], "uniprot_id": "P02724" }, "relationship_type": "biomarker", "source_pmcid": "PMC11080875" }, { "confidence": "medium", "disease": "Erythropoiesis disorders", "glycan_involvement": "N-glycosylation affects receptor trafficking.", "mechanism": "CD71 on reticulocyte-derived EVs indicates maturation stage; abnormal shedding linked to anemia.", "protein": "Transferrin receptor (CD71)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. Th", "gene_name": "TFRC", "glycan_count": 105, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G13041EF", "G29068FM", "G29931IJ", "G43417UB", "G45827ZM", "G49108TO", "G49632WD", "G74722FL", "G80111QD", "G81006GJ", "G00912UN", "G04657PL", "G06247RL", "G07246CJ", "G07810QS", "G08918WF", "G11629QQ", "G11911BT", "G13131HA", "G13191RB", "G14972EH", "G15169WU", "G18183SM", "G20312EM", "G25451PN", "G27058EU", "G27915IV", "G31852PQ", "G34989PA", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G57776ZS", "G60834IK", "G62765YT", "G66621EA", "G66760KM", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70888PK", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81637OR", "G83646BJ", "G84225JN", "G84452RH", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G96577RX", "G98611JV", "G98956LI", "G22768VO", "G38586WN", "G46605MF", "G81315DD", "G06356OH", "G57888GL", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G21001NA", "G26335RK", "G39188ZX", "G41247ZX", "G43947VZ", "G45841FE", "G47909JD", "G48712ZJ", "G62768NK", "G64527OM", "G66538GV", "G74910CR", "G83460ZZ", "G16828VN", "G20425TQ", "G23453IV", "G23863VK", "G25520XG", "G26684GN", "G33609NS", "G36191CD", "G45359RY", "G50045TK", "G51367TM", "G72735IY", "G78059CC", "G79809MM", "G91636VS" ], "uniprot_id": "P02786" }, "relationship_type": "biomarker", "source_pmcid": "PMC11080875" }, { "confidence": "medium", "disease": "Cancer progression", "glycan_involvement": "Glycosylation influences exosome formation.", "mechanism": "Tetraspanins enriched on exosomes facilitate cargo sorting and cell targeting in tumor microenvironment.", "protein": "Tetraspanins (CD9, CD63, CD81)", "relationship_type": "biomarker", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "Tumor progression", "glycan_involvement": "N-glycosylation essential for antigen presentation.", "mechanism": "MHC glycoproteins on DC-derived EVs present tumor antigens, activating anti-tumor immunity.", "protein": "MHC class I/II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "O-glycosylation required for selectin binding.", "mechanism": "PEV-Treg interaction via P-selectin/PSGL-1 modulates IL-17 production, perpetuating inflammation.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "Cancer (gastric, colon)", "glycan_involvement": "N-glycosylation affects surface expression.", "mechanism": "High serum levels of B cell-derived EVs expressing CD39/CD73 correlate with poor progression-free survival.", "protein": "CD39/CD73", "relationship_type": "biomarker", "source_pmcid": "PMC11080875" }, { "confidence": "high", "disease": "DHAV-1 infection", "glycan_involvement": "HSP70 is a glycoprotein; glycosylation may affect its chaperone activity and interactions.", "mechanism": "HSP70 directly interacts with DHAV-1 IRES to promote viral translation, replication, and assembly by stabilizing VP1 and VP3.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "high", "disease": "DHAV-1 infection", "glycan_involvement": "No direct glycosylation reported for VP1 in this study.", "mechanism": "VP1 is stabilized by HSP70, preventing proteasomal degradation and facilitating virion assembly.", "protein": "VP1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "high", "disease": "DHAV-1 infection", "glycan_involvement": "No direct glycosylation reported for VP3 in this study.", "mechanism": "VP3 is stabilized by HSP70, preventing proteasomal degradation and facilitating virion assembly.", "protein": "VP3", "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "EV71 infection", "glycan_involvement": "HSP70 glycosylation may modulate chaperone activity.", "mechanism": "HSP70 stabilizes viral replication complex proteins (2C, 3D) and promotes replication.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "Zika virus infection", "glycan_involvement": "Cell surface glycosylation may facilitate HSP70-virus interaction.", "mechanism": "HSP70 assists in viral adsorption and invasion at the cell surface.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "Dengue virus infection", "glycan_involvement": "Cell surface glycosylation may facilitate HSP70-virus interaction.", "mechanism": "HSP70 assists in viral adsorption and invasion at the cell surface.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "PRRSV infection", "glycan_involvement": "Cell surface glycosylation may facilitate HSP70-virus interaction.", "mechanism": "HSP70 assists in viral adsorption and invasion at the cell surface.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "Rabies virus infection", "glycan_involvement": "Not specified.", "mechanism": "HSP70 promotes viral replication.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "CVB3 infection", "glycan_involvement": "Not specified.", "mechanism": "HSP70 interacts with ARE on poly-A tail to stabilize viral genome and promote replication.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "medium", "disease": "HCV infection", "glycan_involvement": "HSC70 glycosylation may affect interaction with NS5A.", "mechanism": "HSP70 and HSC70 interact with HCV proteins to regulate assembly and particle production.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "causal", "source_pmcid": "PMC11100043" }, { "confidence": "high", "disease": "Diffuse Large B-cell Lymphoma", "glycan_involvement": "Not specified for CD20 in this article.", "mechanism": "CD20 is enriched on sEV from DLBCL cells and detectable in patient plasma, reflecting tumor cell phenotype.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100054" }, { "confidence": "high", "disease": "Diffuse Large B-cell Lymphoma", "glycan_involvement": "High glycosylation of PD-L1 detected on sEV; glycosylation may stabilize PD-L1 and enhance immunosuppressive function.", "mechanism": "Highly glycosylated PD-L1 is present on sEV from DLBCL patients, mirroring tumor immunosuppressive potential.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11100054" }, { "confidence": "high", "disease": "EBV-transformed B cell lymphoproliferative disease", "glycan_involvement": "Glycosylation of PD-L1 is associated with its immunosuppressive activity on T cells.", "mechanism": "High glycosylated PD-L1 on sEV from EBV-transformed B cells induces apoptosis in CD4+ and CD8+ T cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC11100054" }, { "confidence": "high", "disease": "Diffuse Large B-cell Lymphoma", "glycan_involvement": "Glycosylation enhances PD-L1 stability and function on sEV.", "mechanism": "PD-L1+ sEV inhibit activated T cells, contributing to immune evasion in DLBCL.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC11100054" }, { "confidence": "medium", "disease": "Diffuse Large B-cell Lymphoma", "glycan_involvement": "Not specified.", "mechanism": "CD20 on sEV may reflect levels on tumor cells, informing anti-CD20 immunotherapy strategies.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11100054" }, { "confidence": "medium", "disease": "Diffuse Large B-cell Lymphoma", "glycan_involvement": "Glycosylation status may affect detectability and function.", "mechanism": "Circulating sEV PD-L1 levels can serve as a biomarker for immunosuppressive status and potential response to PD-1/PD-L1 blockade.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100054" }, { "confidence": "medium", "disease": "EBV-transformed B cell lymphoproliferative disease", "glycan_involvement": "High glycosylation correlates with function.", "mechanism": "PD-L1+ sEV levels reflect immunosuppressive activity in EBV-driven disease.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100054" }, { "confidence": "high", "disease": "ABCA4-associated inherited retinal disease (IRD)", "glycan_involvement": "Glycosylation affects ABCA4 folding and trafficking in photoreceptors and RPE.", "mechanism": "Mutations and non-coding variants in ABCA4 disrupt cis-regulatory elements and 3D chromatin interactions, affecting tissue-specific expression.", "protein": "ABCA4", "protein_enriched": { "function": "Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) ", "gene_name": "ABCA4", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22768VO", "G49108TO" ], "uniprot_id": "P78363" }, "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "high", "disease": "Retinitis pigmentosa", "glycan_involvement": "N-glycosylation required for RHO stability and function.", "mechanism": "Differential chromatin looping regulates RHO expression in photoreceptors; mutations cause RP.", "protein": "RHO", "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Cone-rod dystrophy", "glycan_involvement": "Glycosylation modulates PROM1 localization in photoreceptors.", "mechanism": "Retina-specific chromatin loops regulate PROM1; mutations disrupt photoreceptor structure.", "protein": "PROM1", "protein_enriched": { "function": "May play a role in cell differentiation, proliferation and apoptosis (PubMed:24556617). Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization", "gene_name": "PROM1", "glycan_count": 40, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G07246CJ", "G37818NZ", "G37995HC", "G41071NU", "G42124LM", "G44215PV", "G57776ZS", "G62765YT", "G69521XL", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G82443XX", "G00912UN", "G06356OH", "G20312EM", "G23863VK", "G26403SG", "G27058EU", "G31916IQ", "G36442WJ", "G37412TK", "G48414YA", "G49955PK", "G58954YZ", "G59626AS", "G65184UU", "G70418MS", "G72667IM", "G75983OB", "G81198YO", "G82463GQ", "G83646BJ", "G84452RH", "G91473PK", "G95977AE", "G98611JV", "G63136LV", "G71463BG" ], "uniprot_id": "O43490" }, "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Macular dystrophy", "glycan_involvement": "Glycosylation influences CDH3-mediated cell-cell adhesion.", "mechanism": "RPE-specific chromatin interactions regulate CDH3; mutations affect cell adhesion.", "protein": "CDH3", "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation affects TIMP3 secretion and activity.", "mechanism": "RPE-specific chromatin loops regulate TIMP3; mutations lead to extracellular matrix dysregulation.", "protein": "TIMP3", "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation modulates EFEMP1 function in extracellular matrix.", "mechanism": "RPE-specific chromatin interactions regulate EFEMP1; mutations cause matrix accumulation.", "protein": "EFEMP1", "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation required for FBLN5 matrix assembly.", "mechanism": "RPE-specific chromatin loops regulate FBLN5; mutations impair elastic fiber formation.", "protein": "FBLN5", "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Leber congenital amaurosis", "glycan_involvement": "Glycosylation affects LRAT enzymatic activity.", "mechanism": "RPE-specific chromatin interactions regulate LRAT; mutations disrupt retinoid metabolism.", "protein": "LRAT", "protein_enriched": { "function": "Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters (PubMed:9920938). Retinyl esters are storage forms of vitamin A (Probabl", "gene_name": "LRAT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95237" }, "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation modulates CFH binding to complement components.", "mechanism": "RPE-specific chromatin interactions increase CFH expression, providing complement regulation.", "protein": "CFH", "relationship_type": "protective", "source_pmcid": "PMC11100165" }, { "confidence": "medium", "disease": "Retinitis pigmentosa", "glycan_involvement": "Glycosylation affects CRB1 localization and function.", "mechanism": "Neural retina-specific chromatin interactions regulate CRB1; mutations disrupt cell polarity.", "protein": "CRB1", "protein_enriched": { "function": "Plays a role in photoreceptor morphogenesis in the retina (By similarity). May maintain cell polarization and adhesion (By similarity)", "gene_name": "CRB1", "glycan_count": 1, "glycosylation_sites_count": 23, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P82279" }, "relationship_type": "causal", "source_pmcid": "PMC11100165" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-glycosylation of hemoglobin correlates with glucose levels.", "mechanism": "HbA1c reflects average blood glucose and is used for diabetes diagnosis and monitoring.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects GGT stability and secretion.", "mechanism": "Elevated GGT is included in FLI and reflects liver dysfunction and steatosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation modulates FPR2 function and cell surface expression.", "mechanism": "Estrogen regulates FPR2 expression, mediating protection against NAFLD/MASLD.", "protein": "Formyl peptide receptor 2 (FPR2)", "protein_enriched": { "function": "Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophil chemotactic factors (PubMed:1374236). Binding of FMLP to the receptor causes activation of neutrophils (PubMed:1374", "gene_name": "FPR2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P25090" }, "relationship_type": "protective", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation required for FGF19 secretion and receptor binding.", "mechanism": "FGF19 (FGF-15/19) signals from gut to liver, regulating bile acid and lipid/glucose metabolism, with sex-specific effects.", "protein": "Fibroblast growth factor 19 (FGF19)", "protein_enriched": { "function": "Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocyte", "gene_name": "FGF19", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95750" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Indirect; LXR activation affects glycan metabolism and glycoprotein expression.", "mechanism": "LXR regulates cholesterol metabolism and is linked to intrahepatic fat, inflammation, and fibrosis.", "protein": "Liver X Receptor (LXR)", "protein_enriched": { "function": "Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920, PubMed:37478846). Interaction with retinoic acid receptor (RXR) shifts RXR from", "gene_name": "NR1H3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13133" }, "relationship_type": "causal", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation of ApoA1 affects HDL function.", "mechanism": "Inverse correlation between HDL and FLI/MASLD; higher HDL is protective.", "protein": "HDL cholesterol (ApoA1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation of ApoB influences LDL metabolism.", "mechanism": "Direct correlation between LDL and FLI/MASLD in men; higher LDL associated with MASLD.", "protein": "LDL cholesterol (ApoB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects AST stability.", "mechanism": "AST is elevated in MASLD and correlates with FLI.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects ALT stability.", "mechanism": "ALT is elevated in MASLD and correlates with FLI.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation of apolipoproteins modulates lipoprotein metabolism.", "mechanism": "Serum triglycerides are central to FLI and reflect hepatic steatosis.", "protein": "Triglyceride-rich lipoproteins (apolipoproteins)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11100212" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Cell surface glycoproteins mediate immune cell interactions and inflammation.", "mechanism": "Elevated WBC indicates inflammation, which is associated with CKD progression.", "protein": "White blood cell (WBC)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "LDL particles are glycosylated, affecting clearance and vascular inflammation.", "mechanism": "Altered LDL-C levels are associated with CKD risk.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "HDL glycosylation modulates its function in inflammation and renal protection.", "mechanism": "HDL-C levels are monitored in CKD; altered glycosylation may affect anti-inflammatory properties.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Indirect; BUN reflects protein metabolism, which is influenced by glycoprotein turnover.", "mechanism": "Elevated BUN is a marker of impaired renal function.", "protein": "Blood urea nitrogen (BUN)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "TG transport involves glycoproteins (e.g., apolipoproteins) affecting renal lipid handling.", "mechanism": "Elevated TG is an independent risk factor for CKD.", "protein": "Triglyceride (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Albumin glycosylation affects its filtration and reabsorption in the kidney.", "mechanism": "Urinary protein (albuminuria) is a diagnostic marker for CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation of hemoglobin (HbA1c) is relevant in diabetic CKD.", "mechanism": "Anemia (low hemoglobin) is common in CKD.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "ALT is glycosylated, affecting its stability and activity.", "mechanism": "Elevated ALT is a marker for liver disease, which is comorbid with CKD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "AST glycosylation modulates its function.", "mechanism": "Elevated AST is a marker for liver disease, which can impact CKD risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycoproteins on WBCs mediate vascular inflammation.", "mechanism": "Elevated WBC is associated with inflammation in hypertension, a CKD risk factor.", "protein": "White blood cell (WBC)", "relationship_type": "biomarker", "source_pmcid": "PMC11100214" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GLP-1 is a glycoprotein; glycosylation may affect stability and receptor interaction.", "mechanism": "GLP-1 increase (via semaglutide) is independently associated with reduction in liver steatosis (CAP reduction).", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11100230" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "IL-18 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-18 levels are elevated in MASLD and reduced by semaglutide, indicating decreased liver inflammation.", "protein": "IL-18 (Interleukin-18)", "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation modulates IL-18 function in inflammation.", "mechanism": "IL-18 implicated in metabolic inflammation in T2D; reduced by semaglutide.", "protein": "IL-18 (Interleukin-18)", "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation may affect GLP-1 receptor binding and half-life.", "mechanism": "GLP-1 analogues (semaglutide) improve glycemic control and weight loss in T2D.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11100230" }, { "confidence": "medium", "disease": "Systemic hyperinflammation", "glycan_involvement": "Glycosylation required for IL-18 secretion and activity.", "mechanism": "IL-18 drives systemic hyperinflammation and amplifies IFN\u03b3 pathways.", "protein": "IL-18 (Interleukin-18)", "relationship_type": "causal", "source_pmcid": "PMC11100230" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect GLP-1 stability and function.", "mechanism": "GLP-1 receptor agonists may reduce liver stiffness, indicating protection against fibrosis.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "protective", "source_pmcid": "PMC11100230" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Insulin is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Insulin resistance is central to T2D; measured as HOMA-IR.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "TNF\u03b1 is glycosylated; glycosylation affects activity.", "mechanism": "TNF\u03b1 is a marker of liver inflammation in MASLD; not significantly changed by semaglutide in this study.", "protein": "TNF\u03b1 (Tumor necrosis factor alpha)", "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "MCP-1 is glycosylated; glycosylation affects chemokine function.", "mechanism": "MCP-1 is a marker of liver inflammation; not significantly changed by semaglutide.", "protein": "MCP-1 (Monocyte chemoattractant protein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "IL-10 is glycosylated; glycosylation affects anti-inflammatory activity.", "mechanism": "IL-10 is anti-inflammatory; levels not significantly changed by semaglutide.", "protein": "IL-10 (Interleukin-10)", "relationship_type": "biomarker", "source_pmcid": "PMC11100230" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Ferritin is N-glycosylated, which affects its stability and serum levels.", "mechanism": "Elevated ferritin promotes MASLD via oxidative stress, insulin resistance, and lipid peroxidation.", "protein": "Serum Ferritin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11100236" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "N-glycosylation influences ferritin secretion and detection.", "mechanism": "High ferritin predicts progression to NASH and hepatic fibrosis.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation may affect ferritin's role in fibrogenesis.", "mechanism": "Elevated ferritin is independently associated with advanced liver fibrosis in MASLD.", "protein": "Serum Ferritin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11100236" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Glycosylation status may modulate ferritin's metabolic effects.", "mechanism": "High ferritin is associated with increased risk of T2DM via insulin resistance.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "medium", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "N-glycosylation impacts serum ferritin levels.", "mechanism": "Elevated ferritin is a marker of MetS severity.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect ferritin's circulatory half-life.", "mechanism": "High ferritin correlates with hypertension risk.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation influences ferritin's serum concentration.", "mechanism": "Elevated ferritin is associated with abnormal lipid profiles.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects ferritin's detectability and stability.", "mechanism": "Longitudinal increase in ferritin trajectory predicts new-onset MASLD.", "protein": "Serum Ferritin", "relationship_type": "predictive biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may modulate ferritin's serum levels.", "mechanism": "Even high-normal ferritin levels (>80 ng/ml) increase MASLD risk.", "protein": "Serum Ferritin", "relationship_type": "risk marker", "source_pmcid": "PMC11100236" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation ensures ferritin's stability for diagnostic use.", "mechanism": "Ferritin included in an 8-variable model improves MASLD risk prediction.", "protein": "Serum Ferritin", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC11100236" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "ALT is not glycosylated; glycosylation not involved", "mechanism": "Elevated ALT levels are positively correlated with insulin resistance indices (glucose, insulin, HOMA-IR, HOMA-\u03b2)", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "AST is not glycosylated; glycosylation not involved", "mechanism": "AST levels are correlated with most insulin resistance indices, though less consistently than ALT", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Neither protein is glycosylated; ratio reflects enzyme activity, not glycosylation", "mechanism": "ALT/AST ratio is a superior predictor of insulin resistance compared to ALT alone, especially in women", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "No glycosylation involvement", "mechanism": "Higher ALT/AST ratio is associated with increased prevalence of diabetes", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No glycosylation involvement", "mechanism": "ALT/AST ratio reflects liver damage and steatosis, which are linked to NAFLD", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "No glycosylation involvement", "mechanism": "ALT/AST ratio is a phenotype marker for metabolic syndrome", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "No glycosylation involvement", "mechanism": "Higher ALT/AST ratio is associated with increased risk of cardiovascular events via insulin resistance", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "No glycosylation involvement", "mechanism": "ALT/AST ratio tertiles are associated with higher prevalence of hypertension", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "No glycosylation involvement", "mechanism": "Higher ALT/AST ratio is associated with increased prevalence of dyslipidemia", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "No glycosylation involvement", "mechanism": "ALT/AST ratio can help identify risk of NASH even when ALT is normal", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11101110" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects average blood glucose and is used to diagnose and monitor diabetes.", "protein": "Glycosylated Hemoglobin A1c (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Insulin is glycosylated, affecting stability and secretion.", "mechanism": "Insulin resistance is central to T2DM pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "C-Peptide is a glycoprotein fragment released during insulin maturation.", "mechanism": "C-Peptide levels indicate endogenous insulin production.", "protein": "C-Peptide", "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and function.", "mechanism": "CRP is an acute-phase reactant elevated in inflammation and predicts CVD risk.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Albumin glycosylation status can change in liver disease.", "mechanism": "Serum albumin levels decrease with worsening liver fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "AST is glycosylated, which may affect its serum half-life.", "mechanism": "Elevated AST is indicative of liver injury and fibrosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "ALT glycosylation may influence enzyme activity.", "mechanism": "ALT elevation signals hepatocellular injury.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation modulates function.", "mechanism": "HDL-C is inversely associated with CVD risk.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC11101429" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "N-glycosylation affects enzyme activity and clearance.", "mechanism": "Elevated alkaline phosphatase is associated with cholestasis and liver fibrosis.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "low", "disease": "Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Serum proteins are variably glycosylated; changes in glycosylation may reflect disease state.", "mechanism": "Altered serum protein levels reflect liver synthetic function in MAFLD.", "protein": "Total Serum Protein", "relationship_type": "biomarker", "source_pmcid": "PMC11101429" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APOE stability and receptor interactions.", "mechanism": "APOE upregulated in microglia, downregulated in astrocytes; influences amyloid-beta transport and neuronal MHC class I expression.", "protein": "APOE", "relationship_type": "causal", "source_pmcid": "PMC11101463" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects CLU secretion and chaperone function.", "mechanism": "CLU is a top AD GWAS risk gene, involved in complement activation and amyloid-beta clearance.", "protein": "CLU", "relationship_type": "risk/biomarker", "source_pmcid": "PMC11101463" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for CR1 cell surface expression and ligand binding.", "mechanism": "CR1 mediates complement activation and phagocytosis in microglia, contributing to amyloid-beta clearance.", "protein": "CR1", "relationship_type": "risk/causal", "source_pmcid": "PMC11101463" }, { "confidence": "high", "disease": "Microglial activation", "glycan_involvement": "N-glycosylation essential for TREM2 folding and function.", "mechanism": "TREM2 regulates microglial phagocytosis of amyloid-beta and apoptotic neurons.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation modulates TYROBP signaling.", "mechanism": "TYROBP is a key regulator of microglial immune module, driving inflammatory response in AD.", "protein": "TYROBP", "relationship_type": "causal", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "O-glycosylation affects SPP1 cytokine activity.", "mechanism": "SPP1 is upregulated in microglia and oligodendrocytes, associated with inflammatory response and cell death.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Copper homeostasis disruption", "glycan_involvement": "N-glycosylation may affect FTH1 stability.", "mechanism": "FTH1 involved in iron/copper storage; dysregulation linked to AD astrocyte response to copper.", "protein": "FTH1", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role ", "gene_name": "Ftl1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29391" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "N-glycosylation regulates NRXN1 synaptic localization.", "mechanism": "NRXN1 prioritized in astrocyte modules; implicated in synaptic maintenance and AD progression.", "protein": "NRXN1", "relationship_type": "biomarker", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Myelin loss", "glycan_involvement": "N-glycosylation may regulate OLIG1 function.", "mechanism": "OLIG1 involved in oligodendrocyte differentiation and myelin repair; disruption linked to early AD pathology.", "protein": "OLIG1", "protein_enriched": { "function": "Promotes formation and maturation of oligodendrocytes, especially within the brain. Cooperates with OLIG2 to establish the pMN domain of the embryonic neural tube (By similarity)", "gene_name": "OLIG1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TAK6" }, "relationship_type": "causal", "source_pmcid": "PMC11101463" }, { "confidence": "medium", "disease": "Neuronal apoptosis", "glycan_involvement": "N-glycosylation modulates BDNF secretion.", "mechanism": "BDNF signaling pathway promotes neuron survival; reduced activity in AD astrocyte modules.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC11101463" }, { "confidence": "high", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Fibrinogen glycosylation affects its stability and function; altered glycosylation may exacerbate coagulopathy.", "mechanism": "Decreased plasma fibrinogen reflects impaired liver synthetic function and coagulopathy in ACLF.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "high", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation modulates procalcitonin secretion and stability.", "mechanism": "Elevated procalcitonin indicates systemic inflammation and infection risk in ACLF.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "high", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "N-glycosylation regulates IL-6 receptor binding and signaling.", "mechanism": "IL-6 drives systemic inflammation and organ failure in ACLF; reduction via CytoSorb may improve outcomes.", "protein": "Interleukin-6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation; altered glycosylation may affect function.", "mechanism": "Decreased platelet count reflects bone marrow suppression and increased consumption in ACLF.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "CRP glycosylation affects its immunomodulatory activity.", "mechanism": "CRP is an acute phase reactant; levels may indicate inflammation but were not significantly changed by CytoSorb.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation is essential for GGT membrane localization and activity.", "mechanism": "Elevated GGT reflects cholestasis and hepatocellular injury in ACLF.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "high", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Albumin glycosylation may affect bilirubin binding and clearance.", "mechanism": "Elevated bilirubin indicates impaired hepatic clearance; CytoSorb removes bilirubin from circulation.", "protein": "Bilirubin-bound albumin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation may influence enzyme stability.", "mechanism": "Elevated AST reflects hepatocellular injury in ACLF.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation may influence enzyme stability.", "mechanism": "Elevated ALT reflects hepatocellular injury in ACLF.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "medium", "disease": "Multi-organ failure", "glycan_involvement": "Altered glycosylation may impair fibrinogen function.", "mechanism": "Low fibrinogen is associated with increased bleeding risk and poor prognosis in multi-organ failure.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101465" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Clusterin is heavily glycosylated, affecting secretion and chaperone activity.", "mechanism": "Upregulated in aqueous humor of smokers; associated with cellular senescence and oxidative stress in AMD.", "protein": "Clusterin (Apolipoprotein J)", "relationship_type": "biomarker", "source_pmcid": "PMC11101467" }, { "confidence": "medium", "disease": "Cataract", "glycan_involvement": "N-glycosylation modulates anti-inflammatory properties.", "mechanism": "Elevated in AH of smokers with cataract risk factors; may protect against inflammation.", "protein": "Alpha-2-HS-glycoprotein (Fetuin-A)", "relationship_type": "biomarker", "source_pmcid": "PMC11101467" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation affects fibrin clot structure and function.", "mechanism": "Smoking increases fibrinogen, promoting prothrombotic state and platelet aggregation.", "protein": "Fibrinogen gamma chain", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "E2R0G7" }, "relationship_type": "causal", "source_pmcid": "PMC11101467" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "N-glycosylation required for stability and anti-inflammatory activity.", "mechanism": "Upregulated in smokers; inhibits proteases and modulates inflammatory cytokines.", "protein": "Alpha-1-antitrypsin", "relationship_type": "protective", "source_pmcid": "PMC11101467" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation influences complement regulatory function.", "mechanism": "Elevated in smokers; inhibits complement, forms complex with protein S, reducing anticoagulant activity.", "protein": "C4b-binding protein alpha chain", "protein_enriched": { "function": "Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation ", "gene_name": "C4BPA", "glycan_count": 28, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G12341GU", "G22310AV", "G27947YN", "G47518TP", "G47737VJ", "G48414YA", "G52527GH", "G59626AS", "G82830MN", "G83633GK", "G88374WZ", "G92551JA", "G94470IW", "G94917XT", "G43417UB", "G29068FM", "G01608SO", "G34617SM", "G49739MP", "G73686WG", "G90093AU", "G26951VZ" ], "uniprot_id": "P04003" }, "relationship_type": "causal", "source_pmcid": "PMC11101467" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates HDL binding and inflammatory activity.", "mechanism": "Upregulated in smokers; promotes inflammation and platelet activation, linked to vascular disease.", "protein": "Serum amyloid A-2", "protein_enriched": { "function": "Major acute phase reactant", "gene_name": "SAA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P0DJI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101467" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "N-glycosylation required for complement activation.", "mechanism": "Downregulated in smokers; complement dysregulation implicated in AMD pathogenesis.", "protein": "Complement factor B", "protein_enriched": { "function": "Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathog", "gene_name": "CFB", "glycan_count": 84, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G04854VP", "G06110VR", "G06356OH", "G08918WF", "G10486CT", "G14972EH", "G15664MX", "G26330YA", "G28681TP", "G43223CG", "G48414YA", "G54010QB", "G55220VL", "G57317CE", "G58954YZ", "G59626AS", "G61256FT", "G63980BQ", "G70619PT", "G72291OX", "G80920RR", "G82463GQ", "G85554PZ", "G87389XI", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G96416FQ", "G53434XO", "G43417UB", "G57321FI", "G00273SJ", "G05933EN", "G06247RL", "G10819WX", "G10846ZT", "G11115RO", "G28622IK", "G31986NC", "G37412TK", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G43669FQ", "G45395BF", "G47737VJ", "G49018RC", "G54612UD", "G59324HL", "G60033FS", "G68735SN", "G70232NH", "G72747WU", "G75418YA", "G82830MN", "G84452RH", "G86182NS", "G92135MA", "G94665LC", "G98611JV", "G01650EU", "G08290VR", "G12341GU", "G27058EU", "G27126ED", "G29184RN", "G46691LC", "G46902YN", "G56307ZW", "G57776ZU", "G58087IP", "G70888PK", "G78787DI", "G81315DD", "G84225JN", "G84349RE", "G88374WZ", "G96091TT", "G49108TO" ], "uniprot_id": "P00751" }, "relationship_type": "causal", "source_pmcid": "PMC11101467" }, { "confidence": "low", "disease": "Glaucoma", "glycan_involvement": "Heparan sulfate glycosylation critical for matrix interactions.", "mechanism": "Downregulated in smokers; affects extracellular matrix and outflow resistance.", "protein": "Basement membrane-specific heparan sulfate proteoglycan core protein (Perlecan)", "relationship_type": "biomarker", "source_pmcid": "PMC11101467" }, { "confidence": "high", "disease": "Cataract", "glycan_involvement": "Glycosylation affects solubility and lens transparency.", "mechanism": "Downregulated in smokers; loss leads to lens opacity and reduced resistance to oxidative stress.", "protein": "Beta-crystallin B2", "protein_enriched": { "function": "Crystallins are the dominant structural components of the vertebrate eye lens", "gene_name": "CRYBB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P43320" }, "relationship_type": "causal", "source_pmcid": "PMC11101467" }, { "confidence": "high", "disease": "Cataract", "glycan_involvement": "Glycosylation modulates protein stability in lens.", "mechanism": "Downregulated in smokers; aggregation leads to lens opacity.", "protein": "Gamma-crystallin S", "protein_enriched": { "function": "Crystallins are the dominant structural components of the vertebrate eye lens", "gene_name": "CRYGS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A140CTX8" }, "relationship_type": "causal", "source_pmcid": "PMC11101467" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Rev binds RRE to mediate nuclear export of intron-containing viral mRNAs, essential for HIV replication.", "protein": "Rev", "relationship_type": "causal", "source_pmcid": "PMC11101469" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "RRE is required for Rev binding and subsequent nuclear export of viral RNAs.", "protein": "Rev response element (RRE)", "relationship_type": "causal", "source_pmcid": "PMC11101469" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "CRM1 is recruited by Rev-RRE complex for nuclear export of viral RNAs.", "protein": "CRM1 (Exportin 1)", "protein_enriched": { "function": "Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on ", "gene_name": "XPO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14980" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11101469" }, { "confidence": "medium", "disease": "AIDS", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "More active Rev variants are associated with advanced disease progression in HIV-positive individuals.", "protein": "Rev", "relationship_type": "causal", "source_pmcid": "PMC11101469" }, { "confidence": "medium", "disease": "AIDS", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "More active RRE variants are associated with advanced disease progression in HIV-positive individuals.", "protein": "Rev response element (RRE)", "relationship_type": "causal", "source_pmcid": "PMC11101469" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Targeting Rev-RRE interaction can inhibit HIV replication by blocking nuclear export of viral RNAs.", "protein": "Rev", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11101469" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Small molecules targeting RRE structure could inhibit Rev binding and HIV replication.", "protein": "Rev response element (RRE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11101469" }, { "confidence": "high", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "CNDP1 is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Low serum CNDP1 (<80 ng/mL) is an independent predictor of MVI in HCC; CNDP1 may regulate cell cycle progression and tissue regeneration.", "protein": "CNDP1", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "LCAT is a glycoprotein; glycosylation may influence its secretion and activity.", "mechanism": "Low LCAT expression in HCC tissue is associated with metastasis and recurrence; LCAT regulates lipid metabolism.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "medium", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "AFP is heavily glycosylated; glycan structures are used in clinical assays.", "mechanism": "Elevated serum AFP is associated with increased risk of MVI in HCC.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "medium", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "CA-125 is a mucin-type glycoprotein; glycosylation is essential for its antigenicity.", "mechanism": "Elevated CA-125 is associated with increased risk of MVI in HCC.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "low", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "CA-19-9 is a sialylated glycan epitope on glycoproteins.", "mechanism": "Elevated CA-19-9 is associated with tumor burden and may correlate with MVI.", "protein": "CA-19-9", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "low", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "CEA is a glycoprotein; glycosylation affects its immunogenicity.", "mechanism": "Elevated CEA may be associated with tumor progression and MVI.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may regulate CNDP1 serum stability.", "mechanism": "Low CNDP1 expression is associated with HCC metastasis and recurrence.", "protein": "CNDP1", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "low", "disease": "Microvascular invasion (MVI) in HCC", "glycan_involvement": "LCAT glycosylation may affect its plasma activity.", "mechanism": "Low serum LCAT is associated with increased risk of MVI in HCC (univariate analysis).", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "low", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may influence CNDP1 serum levels in cirrhosis.", "mechanism": "CNDP1 levels may be altered in cirrhosis, affecting risk stratification for HCC and MVI.", "protein": "CNDP1", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP glycoforms are used for differential diagnosis.", "mechanism": "AFP is a classic serum biomarker for HCC diagnosis and prognosis.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC11101742" }, { "confidence": "high", "disease": "Infectious salmon anemia (ISAv infection)", "glycan_involvement": "HE is a glycoprotein; glycosylation affects receptor binding and immune evasion.", "mechanism": "HE mediates viral entry and virulence; deletions in HE gene increase pathogenicity.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11101871" }, { "confidence": "high", "disease": "Infectious salmon anemia (ISAv infection)", "glycan_involvement": "Fusion protein is glycosylated; glycosylation modulates fusion efficiency.", "mechanism": "Fusion protein enables viral-host membrane fusion for infection.", "protein": "Fusion protein (ISAv segment 5)", "relationship_type": "causal", "source_pmcid": "PMC11101871" }, { "confidence": "high", "disease": "Infectious salmon anemia (ISAv infection)", "glycan_involvement": "Mx is a glycoprotein; glycosylation may affect stability and antiviral activity.", "mechanism": "Mx protein upregulation indicates antiviral interferon response.", "protein": "Mx protein (mxb)", "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "high", "disease": "Sea lice infection (Lepeophtheirus salmonis)", "glycan_involvement": "mhcii is glycosylated; glycosylation is essential for peptide binding and immune recognition.", "mechanism": "Upregulated mhcii reflects antigen presentation and immune activation at parasite attachment sites.", "protein": "Major histocompatibility class II (mhcii)", "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "medium", "disease": "Sea lice infection (Lepeophtheirus salmonis)", "glycan_involvement": "mmp-9 is glycosylated; glycosylation affects secretion and enzymatic activity.", "mechanism": "mmp-9 upregulation is linked to tissue remodeling and wound healing after lice grazing.", "protein": "Matrix metalloprotease 9 (mmp-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "medium", "disease": "Co-infection (ISAv + sea lice)", "glycan_involvement": "CD9 is a glycoprotein; glycosylation modulates cell-cell interactions.", "mechanism": "CD9 upregulation marks T-cell activation during co-infection.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "medium", "disease": "Co-infection (ISAv + sea lice)", "glycan_involvement": "CD28 is glycosylated; glycosylation regulates ligand binding and immune signaling.", "mechanism": "CD28 upregulation indicates enhanced T-cell co-stimulation in response to co-infection.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "medium", "disease": "Co-infection (ISAv + sea lice)", "glycan_involvement": "CD276 is glycosylated; glycosylation affects immune modulation.", "mechanism": "CD276 upregulation reflects immune checkpoint activation during co-infection.", "protein": "CD276", "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "high", "disease": "Co-infection (ISAv + sea lice)", "glycan_involvement": "Glycosylation of HE is critical for immune evasion and increased virulence in co-infection.", "mechanism": "HE glycoprotein facilitates ISAv infection, which is exacerbated by sea lice-induced immunosuppression.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11101871" }, { "confidence": "medium", "disease": "Co-infection (ISAv + sea lice)", "glycan_involvement": "Glycosylation may affect Mx protein antiviral function.", "mechanism": "Mx upregulation is a marker of interferon response to both viral and parasitic challenge.", "protein": "Mx protein (mxb)", "relationship_type": "biomarker", "source_pmcid": "PMC11101871" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry via ACE2 binding; mutations drive immune escape and transmissibility.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11135226" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor binding and antibody accessibility.", "mechanism": "Essential for host cell invasion; mutations increase fitness and virulence.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential O-glycosylation; may affect immune recognition.", "mechanism": "Early positive selection in nucleocapsid region linked to viral genome packaging and immune modulation.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11135226" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Possible glycosylation, but not detailed in article.", "mechanism": "Structural role in virion assembly; mutations may affect virulence.", "protein": "SARS-CoV-2 Envelope protein", "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Possible glycosylation, but not detailed in article.", "mechanism": "Structural protein; mutations may impact viral assembly.", "protein": "SARS-CoV-2 Membrane protein", "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Mutations in ORF3a associated with viral fitness and immune evasion.", "protein": "SARS-CoV-2 ORF3a protein", "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Mutations in NSP2/NSP3/NSP8 linked to increased replication and transmission.", "protein": "SARS-CoV-2 ORF1a/NSP2/NSP3/NSP8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11135226" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Mutations near m6A methylation sites in ORF6 may affect immune evasion.", "protein": "SARS-CoV-2 ORF6 protein", "protein_enriched": { "function": "Disrupts bidirectional nucleocytoplasmic transport by interacting with the host RAE1-NUP98 complex (PubMed:33360543, PubMed:33849972). Disrupts cell nuclear import complex formation by tethering karyo", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC6" }, "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Mutation clusters in ORF7a may modulate immune response.", "protein": "SARS-CoV-2 ORF7a protein", "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Mutation clusters near m6A sites in ORF10 may affect viral fitness.", "protein": "SARS-CoV-2 ORF10 protein", "protein_enriched": { "function": "", "gene_name": "ORF10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A663DJA2" }, "relationship_type": "causal", "source_pmcid": "PMC11135226" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Glycosylation of IIb/IIIa is essential for its function and surface expression, affecting drug binding and efficacy.", "mechanism": "Glycoprotein IIb/IIIa antagonists are used to inhibit platelet aggregation during percutaneous coronary intervention in STEMI patients.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11148306" }, { "confidence": "medium", "disease": "Major adverse cardiac events (MACE)", "glycan_involvement": "Glycosylation modulates receptor conformation and ligand binding.", "mechanism": "Inhibition of IIb/IIIa reduces risk of MACE by preventing thrombus formation during and after PCI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11148306" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects receptor stability and function.", "mechanism": "By reducing platelet aggregation and microvascular obstruction, IIb/IIIa antagonists may lower risk of post-infarction heart failure.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11148306" }, { "confidence": "medium", "disease": "Non-fatal reinfarction", "glycan_involvement": "Glycosylation influences receptor-ligand interactions.", "mechanism": "Antagonism of IIb/IIIa reduces recurrent thrombotic events, lowering reinfarction risk.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11148306" }, { "confidence": "medium", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "CEA is a heavily glycosylated protein; glycosylation affects its stability and detection.", "mechanism": "CEA levels measured pre/post-CRT as part of disease monitoring.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "medium", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "CA19-9 is a sialylated glycan epitope on glycoproteins/lipids; glycosylation is essential for antigenicity.", "mechanism": "CA19-9 levels measured pre/post-CRT as part of disease monitoring.", "protein": "Carbohydrate antigen 19-9 (CA19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "medium", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "Platelet glycoproteins are highly glycosylated; glycosylation modulates platelet function and immune interactions.", "mechanism": "Reduced platelet glycoprotein and volume observed in MSI-H patients; possible link to immune response.", "protein": "Platelet glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "high", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "MLH1 is glycosylated; glycosylation may affect protein stability and localization.", "mechanism": "Loss of MLH1 expression leads to mismatch repair deficiency and MSI-H phenotype.", "protein": "MLH1", "protein_enriched": { "function": "Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t", "gene_name": "MLH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P40692" }, "relationship_type": "causal", "source_pmcid": "PMC11148308" }, { "confidence": "high", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "MSH2 is glycosylated; glycosylation may affect protein stability and localization.", "mechanism": "Loss of MSH2 expression leads to mismatch repair deficiency and MSI-H phenotype.", "protein": "MSH2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismat", "gene_name": "MSH2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50713DU", "G21891JQ", "G49108TO" ], "uniprot_id": "P43246" }, "relationship_type": "causal", "source_pmcid": "PMC11148308" }, { "confidence": "high", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "MSH6 is glycosylated; glycosylation may affect protein stability and localization.", "mechanism": "Loss of MSH6 expression leads to mismatch repair deficiency and MSI-H phenotype.", "protein": "MSH6", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha be", "gene_name": "MSH6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52701" }, "relationship_type": "causal", "source_pmcid": "PMC11148308" }, { "confidence": "high", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "PMS2 is glycosylated; glycosylation may affect protein stability and localization.", "mechanism": "Loss of PMS2 expression leads to mismatch repair deficiency and MSI-H phenotype.", "protein": "PMS2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) o", "gene_name": "PMS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54278" }, "relationship_type": "causal", "source_pmcid": "PMC11148308" }, { "confidence": "medium", "disease": "Locally advanced rectal cancer (LARC)", "glycan_involvement": "Glycosylation of platelet glycoproteins modulates platelet activation and tumor interactions.", "mechanism": "Initial thrombocytosis (high platelet count) predicts poor pathological tumor regression and shorter recurrence-free survival.", "protein": "Platelet glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Platelet glycoprotein glycosylation affects immune modulation and tumor microenvironment.", "mechanism": "PLR (platelet-to-lymphocyte ratio) is associated with tumor stage and response to CRT.", "protein": "Platelet glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "medium", "disease": "Rectal adenocarcinoma (MSI-H/dMMR)", "glycan_involvement": "Glycosylation may influence platelet-mediated immune responses and tumor progression.", "mechanism": "PLR change after CRT is associated with pathologic T-stage; high PLR change linked to better tumor down-staging.", "protein": "Platelet glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11148308" }, { "confidence": "high", "disease": "polyhydramnios", "glycan_involvement": "Glycosylation affects stability and bioactivity of hCG in circulation.", "mechanism": "Elevated free \u03b2-hCG in maternal serum is associated with increased risk of polyhydramnios.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "preeclampsia", "glycan_involvement": "Altered glycosylation may affect placental signaling and hormone clearance.", "mechanism": "High free \u03b2-hCG levels are linked to increased risk of preeclampsia, possibly via placental dysfunction.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "medium", "disease": "hyperlipidemia", "glycan_involvement": "Glycosylation may influence hormone-receptor interactions affecting lipid metabolism.", "mechanism": "Elevated free \u03b2-hCG is associated with increased risk of maternal hyperlipidemia.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "intrauterine growth restriction (IUGR)", "glycan_involvement": "Glycosylation modulates hormone stability and placental signaling.", "mechanism": "High maternal free \u03b2-hCG is associated with increased risk of IUGR, likely due to placental dysfunction.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "adverse pregnancy outcomes (APO)", "glycan_involvement": "Glycosylation state influences hormone half-life and bioactivity.", "mechanism": "Elevated free \u03b2-hCG is a general marker for increased risk of APOs.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "trisomy 21 (Down syndrome)", "glycan_involvement": "Glycosylation affects assay detection and hormone stability.", "mechanism": "Elevated free \u03b2-hCG is used in prenatal screening for trisomy 21.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "trisomy 18", "glycan_involvement": "Glycosylation impacts detection sensitivity.", "mechanism": "Abnormal free \u03b2-hCG levels are used in screening for trisomy 18.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "trisomy 13", "glycan_involvement": "Glycosylation impacts detection sensitivity.", "mechanism": "Abnormal free \u03b2-hCG levels are used in screening for trisomy 13.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "medium", "disease": "low birth weight", "glycan_involvement": "Glycosylation may affect placental hormone function.", "mechanism": "Elevated free \u03b2-hCG is associated with increased risk of low birth weight.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "medium", "disease": "premature delivery", "glycan_involvement": "Glycosylation may modulate hormone clearance and placental signaling.", "mechanism": "High free \u03b2-hCG is associated with increased risk of premature delivery.", "protein": "free beta-subunit human chorionic gonadotropin (free \u03b2-hCG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11149239" }, { "confidence": "high", "disease": "Immunoglobulin G4-related disease (IgG4-RD)", "glycan_involvement": "IgG4 is a glycoprotein; glycosylation affects its immune function and stability.", "mechanism": "IgG4+ plasma cell infiltration and elevated serum IgG4 drive inflammation and fibrosis in multiple organs.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "causal", "source_pmcid": "PMC11149293" }, { "confidence": "high", "disease": "Sinonasal Immunoglobulin G4-related disease", "glycan_involvement": "Glycosylation of IgG4 may modulate its effector functions and tissue deposition.", "mechanism": "IgG4+ plasma cell infiltration in sinonasal tissue leads to chronic inflammation, fibrosis, and mass-like lesions.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "causal", "source_pmcid": "PMC11149293" }, { "confidence": "high", "disease": "Immunoglobulin G4-related disease (IgG4-RD)", "glycan_involvement": "Glycosylation status can affect IgG4 detection and function.", "mechanism": "Elevated serum IgG4 is used as a diagnostic marker for IgG4-RD.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "biomarker", "source_pmcid": "PMC11149293" }, { "confidence": "high", "disease": "Sinonasal Immunoglobulin G4-related disease", "glycan_involvement": "Glycosylation may influence antibody localization and immune complex formation.", "mechanism": "Tissue infiltration by IgG4+ plasma cells and increased IgG4/IgG ratio are diagnostic for sinonasal IgG4-RD.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "biomarker", "source_pmcid": "PMC11149293" }, { "confidence": "medium", "disease": "Chronic rhinosinusitis", "glycan_involvement": "Glycosylation of IgG4 may affect its pro- or anti-inflammatory properties.", "mechanism": "A subset of chronic rhinosinusitis is driven by IgG4+ plasma cell infiltration, as in sinonasal IgG4-RD.", "protein": "Immunoglobulin G4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG4", "glycan_count": 151, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G02886BB", "G03382KH", "G06110VR", "G06356OH", "G07799LX", "G08293MJ", "G10256JP", "G10339FR", "G10486CT", "G12580WI", "G14994KB", "G15038BD", "G16175ZV", "G19379ID", "G20425TQ", "G22310AV", "G23432EQ", "G23505EP", "G23863VK", "G25418HZ", "G25520XG", "G25987BV", "G27126ED", "G27919IH", "G29880MM", "G30159WR", "G31936TA", "G35029YA", "G36191CD", "G40834TG", "G40926MX", "G45504EY", "G46687AB", "G47748JZ", "G49284IH", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G51287LK", "G54600FO", "G58667NI", "G59451NL", "G59536GA", "G59626AS", "G59937CP", "G60033FS", "G61855PQ", "G65092SV", "G65184UU", "G68318VE", "G70418MS", "G71013KY", "G72291OX", "G72787SB", "G72790NZ", "G74430RZ", "G78059CC", "G79568CQ", "G80223IX", "G80475RE", "G80858MF", "G81295CK", "G82830MN", "G83555HU", "G84452RH", "G85740DB", "G85767HW", "G86500WE", "G88374WZ", "G88725PI", "G89993FE", "G90659AW", "G91636VS", "G94854LT", "G95865ZB", "G99966GV", "G02030ZB", "G03127AL", "G05642HQ", "G05724UK", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22140GZ", "G23294PN", "G23453IV", "G24835MQ", "G26403SG", "G31916IQ", "G33609NS", "G33780DA", "G34730YF", "G36836GD", "G37868ZX", "G39188ZX", "G39213VZ", "G39943KJ", "G42358LZ", "G43157UW", "G43694RQ", "G45495MK", "G47518TP", "G48414YA", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G56903ZB", "G57818FI", "G59471TH", "G60145BJ", "G61627IG", "G61937QU", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75798PH", "G75983OB", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G84467IZ", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92129PT" ], "uniprot_id": "P01861" }, "relationship_type": "causal (subset)", "source_pmcid": "PMC11149293" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB100) affecting function and clearance.", "mechanism": "J-shaped association; both low and high LDL-C levels increase diabetes risk, possibly via cholesterol homeostasis disruption.", "protein": "LDL-C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) influencing cholesterol efflux and anti-inflammatory properties.", "mechanism": "L-shaped association; higher HDL-C is protective, possibly via effects on pancreatic beta cells and glycemic control.", "protein": "HDL-C", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "TC reflects sum of cholesterol in glycoprotein-rich lipoproteins.", "mechanism": "J-shaped association; low TC increases diabetes risk, high TC also increases risk after inflection point.", "protein": "TC", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "TG-rich lipoproteins contain glycoproteins affecting metabolism.", "mechanism": "Monotonic positive association; higher TG increases diabetes risk, likely via insulin resistance and altered lipoprotein metabolism.", "protein": "TG", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11149314" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "CETP is a glycoprotein; glycosylation affects its activity and stability.", "mechanism": "CETP mediates transfer of cholesteryl esters from HDL to TG-rich particles, influencing HDL levels and diabetes risk.", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "mechanistic/causal", "source_pmcid": "PMC11149314" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "NPC1L1 is glycosylated; glycosylation modulates its function in cholesterol absorption.", "mechanism": "LDL-C-lowering variants increase diabetes risk; NPC1L1 inhibition (e.g., by ezetimibe) may promote gluconeogenesis.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "causal", "source_pmcid": "PMC11149314" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "HMGCR is glycosylated; glycosylation affects enzyme activity.", "mechanism": "Genetic LDL-C-lowering variants in HMGCR associated with increased diabetes risk.", "protein": "HMGCR", "relationship_type": "causal", "source_pmcid": "PMC11149314" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "PCSK9 is glycosylated; glycosylation regulates secretion and activity.", "mechanism": "LDL-C-lowering variants in PCSK9 increase diabetes risk.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL glycoprotein composition affects atherogenicity and clearance.", "mechanism": "Lowering LDL-C reduces cardiovascular risk but may increase diabetes risk (cholesterol paradox).", "protein": "LDL-C", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL glycoproteins mediate anti-inflammatory and cholesterol efflux functions.", "mechanism": "High HDL-C is protective against cardiovascular disease and diabetes.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC11149314" }, { "confidence": "high", "disease": "COVID-19 (acute)", "glycan_involvement": "Glycosylation required for surface expression and function.", "mechanism": "Elevated EV-CD41A+ indicates platelet activation in COVID-19.", "protein": "CD41A (Glycoprotein IIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Glycosylation modulates platelet adhesion.", "mechanism": "Higher EV-CD41A+ levels in severe cases after week 3.", "protein": "CD41A (Glycoprotein IIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "O-glycosylation essential for selectin binding.", "mechanism": "EV-CD162+ increases in severe/fatal COVID-19 after week 3, reflecting leukocyte-platelet/endothelial interaction.", "protein": "CD162 (PSGL-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19 (acute)", "glycan_involvement": "N-glycosylation affects adhesion properties.", "mechanism": "Elevated EV-CD31+ reflects endothelial dysfunction in COVID-19.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "N-glycosylation modulates endothelial interactions.", "mechanism": "EV-CD31+ levels higher in severe/fatal COVID-19 after week 3.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19-associated coagulopathy", "glycan_involvement": "Glycosylation required for TF activity.", "mechanism": "EV-CD142+ (TF) is increased in COVID-19, associated with hypercoagulability.", "protein": "CD142 (Tissue Factor)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "N-glycosylation influences TF procoagulant function.", "mechanism": "EV-CD142+ levels rise in severe/fatal COVID-19 after week 3.", "protein": "CD142 (Tissue Factor)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "Glycosylation maintains receptor function.", "mechanism": "Persistently elevated EV-CD41A+ may reflect ongoing platelet activation in long COVID.", "protein": "CD41A (Glycoprotein IIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "N-glycosylation impacts chronic adhesion signaling.", "mechanism": "Sustained EV-CD31+ may indicate chronic endothelial dysfunction.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "Hypercoagulability", "glycan_involvement": "Glycosylation required for TF surface expression and activity.", "mechanism": "EV-CD142+ contributes to extrinsic coagulation pathway activation.", "protein": "CD142 (Tissue Factor)", "relationship_type": "causal", "source_pmcid": "PMC11150502" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "Binds to O-glycosylated TF antigen on MUC1 and N-glycans on CD146/MCAM.", "mechanism": "Promotes circulating tumor cell (CTC) adhesion to endothelium via binding to MUC1 and CD44, facilitating extravasation and metastatic seeding.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Binds poly-LacNAc and LacdiNAc on glycoproteins; binding modulated by sialylation.", "mechanism": "Facilitates leukocyte adhesion and migration to inflamed tissues by cross-linking neutrophils and ECs and upregulating adhesion molecules.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Systemic sclerosis", "glycan_involvement": "Targets Gal-3 CRD binding to glycoproteins.", "mechanism": "Neutralizing antibody E07 reduces immune cell infiltration and lung damage.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150550" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "Binds non-sialylated and sialylated glycans on cancer cell and EC surfaces.", "mechanism": "Elevated serum Gal-8 enhances tumor cell adhesion to endothelium, promoting metastatic dissemination.", "protein": "Galectin-8", "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Interacts with integrins and vWF via glycan recognition.", "mechanism": "Promotes leukocyte and platelet adhesion to ECs, contributing to vascular inflammation.", "protein": "Galectin-8", "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "Binds poly-LacNAc and blood group H antigen glycans on ECs and tumor cells.", "mechanism": "High circulating Gal-9 promotes CTC-EC adhesion and metastasis; tumor-intrinsic Gal-9 suppresses metastasis by blocking CD44/integrin interactions.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "dual (protective/causal)", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Binds to blood group H antigen and internal LacNAc residues.", "mechanism": "Enhances leukocyte adhesion to ECs and modulates chemokine/cytokine production.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "O-glycosylation (TF antigen) critical for Gal-3 binding.", "mechanism": "O-glycosylated TF antigen on MUC1 binds Gal-3, exposing adhesion molecules and promoting CTC-EC interaction.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation increases Gal-3 ligand density.", "mechanism": "Highly glycosylated LAMP-1 on metastatic melanoma cells binds EC Gal-3, facilitating lung colonization.", "protein": "LAMP-1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:15121881). Acts as an important regulator o", "gene_name": "Lamp1", "glycan_count": 39, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G65414LI", "G05724UK", "G06110VR", "G14669DU", "G33609NS", "G39188ZX", "G48584BU", "G51672OH", "G64527OM", "G66538GV", "G02815KT", "G23863VK", "G25637MV", "G74724QE", "G82119TF", "G47012YE", "G53677UQ", "G93413PK", "G56940FB", "G26436YP", "G10773YW", "G29898ES", "G41840AI", "G50282JC", "G05962QB", "G11314AS", "G57776ZU", "G93067EQ", "G10039CR", "G39368QD", "G39643OJ", "G65540UB", "G66621EA", "G73585DO", "G76329HL", "G76915KR", "G79896BV", "G62765YT", "G49108TO" ], "uniprot_id": "P11438" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150550" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation of integrins modulates galectin binding.", "mechanism": "Gal-3 and Gal-8 promote integrin-mediated adhesion of tumor and stem cells to ECs, enhancing extravasation.", "protein": "Integrins (\u03b1v\u03b21, \u03b14\u03b21, \u03b15\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11150550" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosyltransferase activity may modify substrate proteins affecting tumor progression and immune microenvironment.", "mechanism": "High GLT8D2 expression correlates with poor prognosis and increased immune cell infiltration, especially macrophages.", "protein": "GLT8D2", "relationship_type": "biomarker", "source_pmcid": "PMC11150579" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may modulate immune evasion via lectin interactions.", "mechanism": "GLT8D2 regulates tumor-associated macrophage polarization and immune cell infiltration, suggesting potential for immunotherapy targeting.", "protein": "GLT8D2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150579" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation of MUC1 by GALNT6 affects cancer cell invasion and chemoresistance.", "mechanism": "GALNT6 promotes breast cancer via abnormal glycosylation of MUC1.", "protein": "GALNT6", "relationship_type": "biomarker", "source_pmcid": "PMC11150579" }, { "confidence": "medium", "disease": "Epstein\u2013Barr virus-associated gastric carcinoma", "glycan_involvement": "Sialyltransferase activity affects glycan structures relevant to tumor phenotype.", "mechanism": "Hypermethylation of ST3GAL6 correlates with EBV-associated gastric carcinomas.", "protein": "ST3GAL6", "relationship_type": "biomarker", "source_pmcid": "PMC11150579" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosyltransferase activity may impact glycan biosynthesis in tumor cells.", "mechanism": "GXYLT2 identified as a potential diagnostic and prognostic biomarker by bioinformatics.", "protein": "GXYLT2", "relationship_type": "biomarker", "source_pmcid": "PMC11150579" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation with \u03b2-1,6-GlcNAc branches alters cell adhesion.", "mechanism": "Overexpression of GnT-V induces mislocalization and dysfunction of E-cadherin, promoting metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC11150579" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation defects impact cell behavior.", "mechanism": "Loss of GALNT6 expression associated with invasion and chemoresistance.", "protein": "GALNT6", "relationship_type": "biomarker", "source_pmcid": "PMC11150579" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation reduces proteasomal degradation of PD-L1.", "mechanism": "N-glycans stabilize PD-L1, enhancing immune inhibitory activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC11150579" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosyltransferase activity modulates signaling pathways.", "mechanism": "GLT8D2/FGFR/PI3K/AKT axis contributes to platinum-based chemotherapy resistance.", "protein": "GLT8D2", "relationship_type": "causal", "source_pmcid": "PMC11150579" }, { "confidence": "low", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect lipid metabolism.", "mechanism": "GLT8D2 negatively regulates microsomal triglyceride transfer protein (MTP) in HepG2 cells.", "protein": "GLT8D2", "relationship_type": "causal", "source_pmcid": "PMC11150579" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Hypo-glycosylated MUC1 increases inflammation; glycosylation state modulates immune cell recruitment.", "mechanism": "Lower MUC1 expression in gut predicts positive response to ustekinumab; high MUC1 linked to inflammation and resistance.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "LCN2 is a glycoprotein released by neutrophils; glycosylation affects stability and immune signaling.", "mechanism": "Lower LCN2 expression in gut predicts response to ustekinumab; LCN2 is induced by Th17 cytokines and marks disease activity.", "protein": "LCN2", "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Putative glycoprotein; glycosylation may affect membrane localization and immune regulation.", "mechanism": "Lower PDZK1IP1 expression in gut predicts response to ustekinumab; regulates immune microenvironment and glucose uptake.", "protein": "PDZK1IP1", "protein_enriched": { "function": "Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide rep", "gene_name": "NDST4", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H3R1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Integrin glycosylation modulates cell adhesion and migration.", "mechanism": "Lower ITGA4 expression in blood and gut associates with response to ustekinumab; involved in lymphocyte trafficking.", "protein": "ITGA4", "protein_enriched": { "function": "Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are al", "gene_name": "ITGA4", "glycan_count": 25, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G15664MX", "G23505EP", "G27058EU", "G31852PQ", "G41071NU", "G42124LM", "G43223CG", "G62765YT", "G80920RR", "G83460ZZ", "G90659AW", "G02815KT", "G11314AS", "G35253PZ", "G41247ZX", "G58087IP", "G81315DD", "G39471UU", "G76868JS", "G85554PZ", "G16125XL", "G82501QM", "G57776ZS", "G45395BF", "G63041LO" ], "uniprot_id": "P13612" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation affects receptor stability and ligand binding.", "mechanism": "Lower IL18R1 expression in gut associates with response to ustekinumab; mediates inflammatory signaling.", "protein": "IL18R1", "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may affect cytokine secretion and activity.", "mechanism": "Lower IL18 expression in blood associates with response to ustekinumab; drives Th1/Th17 activation.", "protein": "IL18", "relationship_type": "biomarker", "source_pmcid": "PMC11150586" }, { "confidence": "high", "disease": "Intestinal fibrosis", "glycan_involvement": "Collagen glycosylation affects ECM structure and fibrosis.", "mechanism": "COL4A1 expression decreases after ustekinumab treatment; marker of ECM and fibrosis.", "protein": "COL4A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Intestinal fibrosis", "glycan_involvement": "Glycosylation required for inhibitor function and stability.", "mechanism": "SERPING1 expression decreases after ustekinumab; involved in fibrosis-related pathways.", "protein": "SERPING1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Intestinal fibrosis", "glycan_involvement": "Glycosylation modulates cell-cell interactions.", "mechanism": "ICAM1 expression decreases after ustekinumab; mediates leukocyte adhesion and fibrosis.", "protein": "ICAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150586" }, { "confidence": "medium", "disease": "Intestinal fibrosis", "glycan_involvement": "Glycosylation affects enzyme activity and substrate specificity.", "mechanism": "MMP1 expression decreases after ustekinumab; involved in ECM remodeling and fibrosis.", "protein": "MMP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150586" }, { "confidence": "high", "disease": "X-linked hypophosphatemia (XLH)", "glycan_involvement": "Glycosylation sites in PHEX are important for its enzymatic activity and structural integrity; loss may impair function.", "mechanism": "Loss-of-function variants in PHEX cause XLH by disrupting phosphate metabolism and bone mineralization.", "protein": "PHEX", "protein_enriched": { "function": "Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weig", "gene_name": "KIN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60870" }, "relationship_type": "causal", "source_pmcid": "PMC11150636" }, { "confidence": "high", "disease": "X-linked hypophosphatemia (XLH)", "glycan_involvement": "Truncation removes multiple glycosylation sites, affecting protein folding and function.", "mechanism": "Exonic variants (c.617T>G p.Leu206Trp, c.621T>A p.Tyr207*) cause aberrant splicing, leading to truncated PHEX lacking glycosylation and zinc-binding domains.", "protein": "PHEX", "protein_enriched": { "function": "Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weig", "gene_name": "KIN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60870" }, "relationship_type": "causal", "source_pmcid": "PMC11150636" }, { "confidence": "high", "disease": "X-linked hypophosphatemia (XLH)", "glycan_involvement": "Truncation eliminates glycosylation sites, impairing protein stability and function.", "mechanism": "Variant c.1700G>C p.Arg567Pro activates cryptic splice site, causing intron retention and truncated PHEX lacking glycosylation and enzymatic domains.", "protein": "PHEX", "protein_enriched": { "function": "Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weig", "gene_name": "KIN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60870" }, "relationship_type": "causal", "source_pmcid": "PMC11150636" }, { "confidence": "high", "disease": "X-linked hypophosphatemia (XLH)", "glycan_involvement": "Loss of glycosylation impairs PHEX's ability to regulate mineralization.", "mechanism": "Truncated PHEX proteins lack zinc-binding and glycosylation sites, disrupting interaction with ASARM peptides and bone mineralization.", "protein": "PHEX", "protein_enriched": { "function": "Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weig", "gene_name": "KIN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60870" }, "relationship_type": "causal", "source_pmcid": "PMC11150636" }, { "confidence": "high", "disease": "X-linked hypophosphatemia (XLH)", "glycan_involvement": "Premature truncation prevents glycosylation of extracellular domain.", "mechanism": "Aberrant splicing from exonic variants leads to premature stop codons and loss of functional glycoprotein.", "protein": "PHEX", "protein_enriched": { "function": "Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weig", "gene_name": "KIN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O60870" }, "relationship_type": "causal", "source_pmcid": "PMC11150636" }, { "confidence": "high", "disease": "Chikungunya fever (CHIKF)", "glycan_involvement": "Glycosylation of E2 modulates receptor binding and immune evasion.", "mechanism": "E2 mediates viral entry by binding to host receptors (e.g., MXRA8, PHB1, CD147), facilitating infection.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "high", "disease": "Chikungunya fever (CHIKF)", "glycan_involvement": "Glycosylation affects fusion efficiency and immune recognition.", "mechanism": "E1 mediates membrane fusion during viral entry; interacts with host receptors.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "high", "disease": "Chikungunya fever (CHIKF)", "glycan_involvement": "Glycosylation of MXRA8 may influence receptor-virus interaction.", "mechanism": "MXRA8 is a key entry receptor for CHIKV and other arthritogenic alphaviruses; blocking MXRA8 reduces infection.", "protein": "MXRA8", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11150648" }, { "confidence": "high", "disease": "Venezuelan equine encephalitis", "glycan_involvement": "Contains LA domains with potential glycosylation sites affecting ligand binding.", "mechanism": "LDLRAD3 is essential for VEEV entry into neuronal cells; blocking LDLRAD3 inhibits infection.", "protein": "LDLRAD3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11150648" }, { "confidence": "high", "disease": "Eastern equine encephalitis", "glycan_involvement": "O-linked glycosylation in membrane-proximal domain may affect receptor function.", "mechanism": "VLDLR mediates EEEV entry; soluble VLDLR LBD-Fc fusion protein protects against infection.", "protein": "VLDLR", "protein_enriched": { "function": "Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Also binds to a wide range of other molecu", "gene_name": "VLDLR", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G28541PG", "G43417UB", "G57321FI", "G82501QM" ], "uniprot_id": "P98155" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11150648" }, { "confidence": "medium", "disease": "Semliki Forest virus infection", "glycan_involvement": "Glycosylation may modulate ligand binding.", "mechanism": "ApoER2 acts as an entry receptor for SFV, facilitating infection.", "protein": "ApoER2", "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "medium", "disease": "Western equine encephalitis", "glycan_involvement": "Multiple O-linked glycosylation sites in LDLR may affect viral binding.", "mechanism": "LDLR serves as a low-affinity receptor for WEEV, EEEV, and SFV entry into neuronal cells.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "medium", "disease": "Chikungunya fever (CHIKF)", "glycan_involvement": "Glycosylation of PHB1 may influence virus-receptor interaction.", "mechanism": "PHB1 interacts with CHIKV E2, mediating viral entry in human cells.", "protein": "PHB1", "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "medium", "disease": "Chikungunya fever (CHIKF)", "glycan_involvement": "Heavily glycosylated; glycan moieties may modulate viral binding.", "mechanism": "CD147 facilitates CHIKV entry and replication; blocking CD147 reduces infection.", "protein": "CD147", "protein_enriched": { "function": "Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photor", "gene_name": "BSG", "glycan_count": 62, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G49108TO", "G01160VV", "G02815KT", "G05049YU", "G08918WF", "G10488MI", "G15127JD", "G15664MX", "G23719VF", "G27058EU", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G50856PC", "G53075ES", "G57776ZS", "G59626AS", "G62765YT", "G65414LI", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G74381CZ", "G77330BQ", "G79666IR", "G80075MS", "G80920RR", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G29068FM", "G43417UB", "G05724UK", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G20210JR", "G20528HD", "G23294PN", "G28681TP", "G32788FZ", "G35541EV", "G46275YY", "G47644PP", "G49755GI", "G60967DT", "G64527OM", "G70101JE", "G70619PT", "G80479JV", "G83460ZZ", "G85269DF", "G92062TF", "G93718GY", "G50713DU" ], "uniprot_id": "P35613" }, "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "medium", "disease": "Sindbis fever", "glycan_involvement": "Glycosylation may affect receptor conformation and virus binding.", "mechanism": "Laminin receptor is the primary receptor for SINV entry into mammalian cells.", "protein": "Laminin receptor", "relationship_type": "causal", "source_pmcid": "PMC11150648" }, { "confidence": "high", "disease": "Primary Membranous Nephropathy (PMN)", "glycan_involvement": "PLA2R is a glycoprotein; glycosylation may affect antigenicity and immune complex formation.", "mechanism": "Autoantibodies bind PLA2R on podocytes, forming immune complexes that deposit subepithelially and activate complement.", "protein": "Phospholipase A2 receptor (PLA2R)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11150713" }, { "confidence": "high", "disease": "Henoch-Sch\u00f6nlein Purpura Nephritis (HSPN)", "glycan_involvement": "Aberrant O-glycosylation (galactose-deficiency) of IgA1 is central to pathogenicity.", "mechanism": "Circulating galactose-deficient IgA1 forms immune complexes that deposit in glomeruli, triggering inflammation.", "protein": "Galactose-deficient IgA1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11150713" }, { "confidence": "medium", "disease": "Primary Membranous Nephropathy (PMN)", "glycan_involvement": "MAC components are glycoproteins; glycosylation affects assembly and function.", "mechanism": "MAC formation on glomerular capillaries leads to podocyte injury and proteinuria.", "protein": "Membrane Attack Complex (MAC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11150713" }, { "confidence": "medium", "disease": "Type 2 Diabetic Kidney Disease (DKD)", "glycan_involvement": "Albumin is glycosylated; glycation (AGE formation) increases in diabetes, affecting renal handling.", "mechanism": "Loss of albumin in urine (albuminuria) reflects glomerular barrier damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150713" }, { "confidence": "high", "disease": "Type 2 Diabetic Kidney Disease (DKD)", "glycan_involvement": "Non-enzymatic glycation of proteins alters structure/function, driving pathology.", "mechanism": "AGEs accumulate due to hyperglycemia, promoting inflammation and fibrosis in glomeruli.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC11150713" }, { "confidence": "high", "disease": "Primary Membranous Nephropathy (PMN)", "glycan_involvement": "Glycosylation may influence PLA2R antibody binding and clearance.", "mechanism": "Serum PLA2R antibody status is used to monitor response to therapy (e.g., TWP, glucocorticoids).", "protein": "Phospholipase A2 receptor (PLA2R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150713" }, { "confidence": "high", "disease": "IgA Vasculitis", "glycan_involvement": "O-glycosylation defect is pathogenic.", "mechanism": "Galactose-deficient IgA1 triggers vasculitis via immune complex deposition.", "protein": "Galactose-deficient IgA1", "relationship_type": "causal", "source_pmcid": "PMC11150713" }, { "confidence": "medium", "disease": "Henoch-Sch\u00f6nlein Purpura Nephritis (HSPN)", "glycan_involvement": "Glycosylation of complement proteins affects MAC formation.", "mechanism": "MAC deposition contributes to glomerular injury in HSPN.", "protein": "Membrane Attack Complex (MAC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11150713" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "PLA2R antibody positivity is associated with progression to CKD in PMN.", "protein": "Phospholipase A2 receptor (PLA2R)", "relationship_type": "biomarker", "source_pmcid": "PMC11150713" }, { "confidence": "low", "disease": "Henoch-Sch\u00f6nlein Purpura Nephritis (HSPN)", "glycan_involvement": "Glycosylation/glycation status may affect albumin loss.", "mechanism": "Hypoalbuminemia reflects severity of glomerular injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150713" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP reflects systemic inflammation and predicts poor prognosis in sepsis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect its half-life and binding properties.", "mechanism": "Low serum albumin indicates malnutrition and inflammation, associated with poor outcomes in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Surface glycoproteins mediate immune cell interactions; glycosylation regulates immune responses.", "mechanism": "Lymphocytopenia reflects immune suppression and predicts increased mortality in sepsis.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased risk of AKI in sepsis patients.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may influence albumin's renal handling.", "mechanism": "Hypoalbuminemia is linked to higher AKI risk in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects CRP's role in inflammation and cancer.", "mechanism": "CRP is part of the CALLY index, which predicts prognosis in HCC.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect albumin's stability in cancer.", "mechanism": "Albumin levels in the CALLY index predict survival in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation modulates CRP's inflammatory signaling.", "mechanism": "CRP in the CALLY index is associated with prognosis in colorectal cancer.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may impact albumin's function in cancer.", "mechanism": "Albumin as part of the CALLY index predicts outcomes in lung cancer.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "medium", "disease": "Distal cholangiocarcinoma", "glycan_involvement": "Glycosylation influences CRP's activity in cancer.", "mechanism": "CRP in the CALLY index predicts long-term outcomes after surgery.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150768" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "MOG is a target antigen in MS and EAE, used to induce demyelination and neuroinflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11150779" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MHC II is N-glycosylated, which affects peptide presentation and immune activation.", "mechanism": "MHC II expression on CNS myeloid cells is associated with neuroinflammation and disease progression.", "protein": "Major histocompatibility complex class II (MHC II)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11150779" }, { "confidence": "high", "disease": "Nasu-Hakola disease", "glycan_involvement": "TREM2 is a glycoprotein; glycosylation may affect receptor function and microglial signaling.", "mechanism": "TREM2 mutations cause early-onset dementia and demyelination.", "protein": "Triggering receptor expressed on myeloid cells 2 (TREM2)", "relationship_type": "causal", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation may regulate TREM2 surface expression and ligand binding.", "mechanism": "TREM2 signaling modulates microglial activation in neurodegeneration.", "protein": "Triggering receptor expressed on myeloid cells 2 (TREM2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD45 is heavily glycosylated; glycosylation modulates cell-cell interactions.", "mechanism": "CD45+ myeloid cells infiltrate CNS during neuroinflammation.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD206 is a glycoprotein; glycosylation is essential for ligand binding.", "mechanism": "CD206+ myeloid cells indicate anti-inflammatory/regenerative phenotype in CNS.", "protein": "CD206 (mannose receptor)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD4 is N-glycosylated; glycosylation affects T cell activation.", "mechanism": "CD4+ T cells drive autoimmune neuroinflammation in MS/EAE.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11150779" }, { "confidence": "high", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may influence immunogenicity of MOG in EAE.", "mechanism": "MOG peptide immunization induces EAE, modeling MS pathology.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may affect TREM2 function in microglia.", "mechanism": "TREM2 signaling is required for microglial-mediated CNS repair; loss leads to demyelination.", "protein": "Triggering receptor expressed on myeloid cells 2 (TREM2)", "relationship_type": "protective/causal", "source_pmcid": "PMC11150779" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "N-glycosylation modulates MHC II function.", "mechanism": "MHC II upregulation marks CNS inflammation in EAE.", "protein": "Major histocompatibility complex class II (MHC II)", "relationship_type": "biomarker", "source_pmcid": "PMC11150779" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "M protein is non-glycosylated; glycosylation not directly involved in epitope function.", "mechanism": "CTL epitopes (M27, M39, M49) from the M protein, restricted by SLA Hp-4.0 haplotype, induce cell-mediated immune responses (PBMC proliferation, IFN-\u03b3 secretion) and are candidates for peptide-based vaccine development.", "protein": "PRRSV membrane (M) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11150780" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "No glycosylation on M protein; immune recognition is peptide-based.", "mechanism": "Presentation of conserved CTL epitopes from M protein on SLA class I molecules leads to effective cellular immunity and potential protection against PRRSV.", "protein": "PRRSV membrane (M) protein", "relationship_type": "protective", "source_pmcid": "PMC11150780" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "No glycosylation; biomarker function is epitope-based.", "mechanism": "M protein-derived CTL epitopes (M27, M39, M49) can be used to monitor CD8+ T-cell responses in pigs with SLA Hp-4.0 haplotype.", "protein": "PRRSV membrane (M) protein", "relationship_type": "biomarker", "source_pmcid": "PMC11150780" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "O-linked sialylation increases tumor aggressiveness.", "mechanism": "ST3GAL1-associated O-linked sialylation predicts poor prognosis and is enriched in advanced GB stages.", "protein": "ST3GAL1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "Core fucosylation modulates signaling and drug resistance.", "mechanism": "FUT8 deregulation contributes to GB tumorigenesis and temozolomide resistance via altered fucosylation of receptor tyrosine kinases.", "protein": "FUT8", "relationship_type": "causal", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "N-glycosylation affects protein folding and tumor progression.", "mechanism": "ALG3 is part of the nine-gene glyco-model; high expression correlates with poor prognosis.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "Modifies glycan branching, impacting cell signaling.", "mechanism": "Included in glyco-model; expression stratifies GB risk and outcome.", "protein": "B3GNT5", "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "O-glycosylation chaperone, affects mucin-type glycoproteins.", "mechanism": "Part of glyco-model; expression linked to GB prognosis.", "protein": "C1GALT1C1", "protein_enriched": { "function": "Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance. Associates with the striatin-interacting ", "gene_name": "CTTNBP2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8WZ74" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "Sulfation of glycosaminoglycans alters tumor microenvironment.", "mechanism": "Part of glyco-model; expression stratifies GB risk.", "protein": "CHST15", "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "Initiates O-glycosylation, modulating cell adhesion.", "mechanism": "Part of glyco-model; expression correlates with GB outcome.", "protein": "GALNT9", "protein_enriched": { "function": "", "gene_name": "RNF148", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N7C7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "Heparan sulfate modification affects growth factor signaling.", "mechanism": "Part of glyco-model; expression linked to prognosis.", "protein": "HS3ST3B1", "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "O-fucosylation modulates Notch signaling.", "mechanism": "Part of glyco-model; expression stratifies risk.", "protein": "MFNG", "protein_enriched": { "function": "May be required for replication-independent chromatin assembly. May serve as a negative regulator of T-cell receptor (TCR) signaling via inhibition of calcineurin. Inhibition of activated calcineurin ", "gene_name": "CABIN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "Glioblastoma (GB)", "glycan_involvement": "UDP-galactose transport affects glycoprotein biosynthesis.", "mechanism": "Part of glyco-model; expression correlates with GB prognosis.", "protein": "SLC35A2", "relationship_type": "biomarker", "source_pmcid": "PMC11150821" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "IL-6 is glycosylated, affecting stability and secretion.", "mechanism": "Elevated IL-6 levels correlate with disease severity and hyperinflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "N-glycosylation modulates receptor function and antibody binding.", "mechanism": "IL-6R mediates IL-6 signaling; blockade reduces inflammation.", "protein": "IL-6 Receptor (IL-6R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11151130" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Therapeutic antibody glycosylation affects efficacy and half-life.", "mechanism": "Blocks IL-6R to dampen cytokine storm; clinical benefit not significant in this trial.", "protein": "Tocilizumab (anti-IL-6R mAb)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC11151130" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "CRP glycosylation influences ligand binding and clearance.", "mechanism": "CRP levels rise with inflammation and disease severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Glycosylation affects ferritin stability and immune recognition.", "mechanism": "Elevated ferritin reflects hyperinflammation and poor prognosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Glycosylation influences fragment clearance.", "mechanism": "High D-dimer indicates coagulopathy and risk of thrombosis.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "N-glycosylation critical for antigen presentation.", "mechanism": "Reduced HLA-DR expression on monocytes correlates with immune suppression in severe COVID-19.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Extensive N- and O-glycosylation shields epitopes from immune detection.", "mechanism": "Spike glycoprotein mediates viral entry and immune evasion.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC11151130" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "CD14 monocyte levels decrease with high IL-6, indicating immune dysfunction.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "low", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Minor glycosylation may affect stability.", "mechanism": "Elevated LDH reflects tissue damage and severity.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151130" }, { "confidence": "high", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "Cytokeratins are glycoproteins; glycosylation may affect stability and detection.", "mechanism": "Positive immunostaining supports epithelial origin of tumor cells.", "protein": "Cytokeratin (pan)", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "high", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Positive immunostaining helps subtype NSCLC.", "protein": "Cytokeratin 7", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell adhesion.", "mechanism": "Vascular marker; positive staining indicates tumor vascularization.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "TTF-1 is a glycoprotein; glycosylation may affect detection.", "mechanism": "Negative staining helps distinguish SMARCA4-dNSCLC from other lung cancers.", "protein": "Thyroid transcription factor 1 (TTF-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "Napsin A is glycosylated; glycosylation may affect stability.", "mechanism": "Negative staining supports diagnosis of non-adenocarcinoma subtype.", "protein": "Napsin A", "protein_enriched": { "function": "May be involved in processing of pneumocyte surfactant precursors", "gene_name": "NAPSA", "glycan_count": 76, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G07246CJ", "G07755XJ", "G08290VR", "G08918WF", "G10819WX", "G11314AS", "G12341GU", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23505EP", "G23719VF", "G25079LO", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G35029YA", "G36379GD", "G37412TK", "G37509XX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43769HG", "G45395BF", "G45504EY", "G47644PP", "G49018RC", "G49906RN", "G49955PK", "G50282JC", "G54010QB", "G57317CE", "G57776ZU", "G58954YZ", "G60033FS", "G62765YT", "G63980BQ", "G65184UU", "G68490OW", "G69521XL", "G70619PT", "G72787SB", "G72790NZ", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83633GK", "G83646BJ", "G84225JN", "G84349RE", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G87123QX", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92050GC", "G92275SC", "G95177YH", "G95865ZB" ], "uniprot_id": "O96009" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "CgA is glycosylated; glycosylation affects secretion and detection.", "mechanism": "Negative staining rules out neuroendocrine differentiation.", "protein": "Chromogranin A (CgA)", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "CD56 is a neural cell adhesion glycoprotein; glycosylation critical for function.", "mechanism": "Negative staining rules out neuroendocrine phenotype.", "protein": "CD56", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "medium", "disease": "SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC)", "glycan_involvement": "Synaptophysin is glycosylated; glycosylation may affect detection.", "mechanism": "Negative staining rules out neuroendocrine differentiation.", "protein": "Synaptophysin (SYN)", "relationship_type": "biomarker", "source_pmcid": "PMC11151270" }, { "confidence": "high", "disease": "Primary membranous nephropathy (PMN)", "glycan_involvement": "PLA2R is a glycoprotein; glycosylation may affect antigenicity and autoantibody binding.", "mechanism": "Anti-PLA2R autoantibodies are present in serum and are diagnostic for PMN; their titers correlate with disease activity.", "protein": "M-type phospholipase A2 receptor (PLA2R)", "relationship_type": "biomarker", "source_pmcid": "PMC11151391" }, { "confidence": "high", "disease": "Primary membranous nephropathy (PMN)", "glycan_involvement": "Glycosylation of PLA2R may modulate immune recognition and pathogenicity.", "mechanism": "Autoimmune response against PLA2R leads to immune complex deposition in glomeruli, causing PMN.", "protein": "M-type phospholipase A2 receptor (PLA2R)", "relationship_type": "causal", "source_pmcid": "PMC11151391" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Albumin is glycosylated; glycan status may affect stability and renal handling.", "mechanism": "Low serum albumin is a hallmark of nephrotic syndrome due to proteinuria.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11151391" }, { "confidence": "medium", "disease": "End-stage renal disease", "glycan_involvement": "Glycosylation may influence PLA2R immunogenicity and disease progression.", "mechanism": "Persistent high anti-PLA2R antibody titers are associated with progression to end-stage renal disease in PMN.", "protein": "M-type phospholipase A2 receptor (PLA2R)", "relationship_type": "biomarker", "source_pmcid": "PMC11151391" }, { "confidence": "medium", "disease": "Primary membranous nephropathy (PMN)", "glycan_involvement": "Targeting glycosylated epitopes may improve immunotherapy specificity.", "mechanism": "Reduction of anti-PLA2R antibodies is a therapeutic goal in PMN management.", "protein": "M-type phospholipase A2 receptor (PLA2R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11151391" }, { "confidence": "medium", "disease": "Primary membranous nephropathy (PMN)", "glycan_involvement": "Glycosylation may affect albumin's half-life and renal loss.", "mechanism": "Serum albumin levels reflect disease severity and response to therapy in PMN.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11151391" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "EpCAM is a glycoprotein; glycosylation may affect EV sorting and detection.", "mechanism": "EpCAM-positive EVs are elevated in breast cancer patient plasma and used for diagnosis.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "MUC1 is heavily O-glycosylated; glycosylation influences EV incorporation and immune recognition.", "mechanism": "MUC1-positive EVs are more abundant in breast cancer patients, aiding diagnosis.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "CD24 glycosylation may affect EV surface presentation and antibody recognition.", "mechanism": "CD24-positive EVs detected with high sensitivity in ovarian cancer patients using hydrogel-based biosensors.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation of EpCAM may modulate EV sorting and immunoaffinity capture.", "mechanism": "EpCAM-positive EVs isolated from plasma for early HCC detection.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "ASGPR1 is a glycoprotein; glycosylation may affect ligand binding and EV targeting.", "mechanism": "ASGPR1-positive EVs used for HCC-specific EV isolation and diagnosis.", "protein": "ASGPR1", "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "PD-L1 glycosylation influences stability and immune evasion; may affect EV sorting.", "mechanism": "PD-L1-positive EVs detected in lung cancer patient samples for cancer management.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "CD63 is glycosylated; glycosylation may affect EV biogenesis and detection.", "mechanism": "CD63-positive EVs are quantified for breast cancer diagnosis and classification.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Nucleolin is glycosylated; glycosylation may influence EV sorting.", "mechanism": "Nucleolin-positive EVs detected in lung cancer for diagnosis and monitoring.", "protein": "Nucleolin", "protein_enriched": { "function": "Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding t", "gene_name": "NCL", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G18647XP", "G37399XV", "G41247ZX", "G68735SN" ], "uniprot_id": "P19338" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "PSA is glycosylated; glycosylation may affect EV incorporation and detection.", "mechanism": "PSA mRNA detected in EVs for ultrasensitive prostate cancer diagnosis.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation may affect EV surface properties and viral RNA association.", "mechanism": "CD63-positive EVs used to capture and detect SARS-CoV-2 RNA in plasma.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11151817" }, { "confidence": "high", "disease": "Rett syndrome", "glycan_involvement": "MECP2 binding is specific to 5mC (a DNA modification, not a classical glycan), not 5hmC; no direct protein glycosylation described.", "mechanism": "Mutations in MECP2 disrupt its binding to 5mC, altering epigenetic regulation and leading to Rett syndrome.", "protein": "Methyl-CpG binding protein 2 (MECP2)", "relationship_type": "causal", "source_pmcid": "PMC11151843" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Epigenetic DNA modifications (5mC/5hmC) modulate MECP2 binding; not classical protein glycosylation.", "mechanism": "Altered 5mC and 5hmC levels affect MECP2 binding, impacting gene expression in cancer.", "protein": "Methyl-CpG binding protein 2 (MECP2)", "relationship_type": "biomarker", "source_pmcid": "PMC11151843" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "GPVI is a glycoprotein; glycosylation is essential for its structure and function in platelet-collagen interactions.", "mechanism": "GPVI mediates platelet activation and aggregation, contributing to sepsis-induced microthrombosis and organ dysfunction; inhibition by Cath-HG reduces these effects.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Glycosylation of GPVI supports its role in platelet adhesion and activation.", "mechanism": "GPVI-mediated platelet activation promotes DIC by driving excessive platelet aggregation and fibrin formation.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "GPVI glycosylation maintains receptor stability and function.", "mechanism": "Overactivation of GPVI leads to excessive platelet consumption, resulting in thrombocytopenia during sepsis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Microthrombosis", "glycan_involvement": "Glycosylation is required for GPVI-collagen binding.", "mechanism": "GPVI activation by collagen triggers platelet aggregation and microthrombus formation in organs during sepsis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Multiple Organ Dysfunction Syndrome (MODS)", "glycan_involvement": "GPVI glycosylation is necessary for its pathological role.", "mechanism": "GPVI-driven platelet activation and microthrombosis contribute to organ damage and MODS in sepsis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Targeting glycosylated GPVI disrupts its function.", "mechanism": "Inhibition of GPVI by Cath-HG reduces platelet activation, microthrombosis, and organ damage, improving survival in sepsis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "protective", "source_pmcid": "PMC11151873" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects GPVI detection and function.", "mechanism": "GPVI expression/activity reflects platelet activation status in sepsis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "biomarker", "source_pmcid": "PMC11151873" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may influence GPVI interactions with immune cells.", "mechanism": "GPVI inhibition (by Cath-HG or anti-GPVI agents) reduces neutrophil activation and NETs formation, mitigating inflammation.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation is critical for GPVI signaling.", "mechanism": "GPVI crosslinking activates downstream Src/Syk/PLC\u03b32/Akt signaling, driving platelet aggregation and inflammation.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC11151873" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation status may affect therapeutic efficacy.", "mechanism": "Combined anti-GPVI and antibacterial therapy may synergistically treat sepsis by reducing thrombosis and bacterial load.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11151873" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Piezo1 is a glycoprotein; glycosylation may affect channel function and localization, but not directly studied here.", "mechanism": "Piezo1 upregulation in macrophages enhances efferocytosis and promotes resolution of fibrosis via stiffness sensing and phagosome acidification.", "protein": "Piezo1", "protein_enriched": { "function": "Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (", "gene_name": "PIEZO1", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G41071NU", "G62765YT", "G67031OU", "G07246CJ", "G25079LO", "G27058EU", "G40574BA", "G70441OD", "G80920RR", "G90659AW" ], "uniprot_id": "Q92508" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation status not directly addressed.", "mechanism": "Piezo1 expression correlates with fibrosis severity and collagen gene expression in NASH.", "protein": "Piezo1", "protein_enriched": { "function": "Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (", "gene_name": "PIEZO1", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G41071NU", "G62765YT", "G67031OU", "G07246CJ", "G25079LO", "G27058EU", "G40574BA", "G70441OD", "G80920RR", "G90659AW" ], "uniprot_id": "Q92508" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation may modulate Piezo1 function.", "mechanism": "Piezo1 activation in macrophages promotes pro-inflammatory cytokine production and exacerbates fibrosis.", "protein": "Piezo1", "protein_enriched": { "function": "Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (", "gene_name": "PIEZO1", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G41071NU", "G62765YT", "G67031OU", "G07246CJ", "G25079LO", "G27058EU", "G40574BA", "G70441OD", "G80920RR", "G90659AW" ], "uniprot_id": "Q92508" }, "relationship_type": "causal", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation may modulate Piezo1 function.", "mechanism": "Piezo1 activation by cyclic stretch in macrophages increases inflammation and fibrosis.", "protein": "Piezo1", "protein_enriched": { "function": "Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (", "gene_name": "PIEZO1", "glycan_count": 11, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G41071NU", "G62765YT", "G67031OU", "G07246CJ", "G25079LO", "G27058EU", "G40574BA", "G70441OD", "G80920RR", "G90659AW" ], "uniprot_id": "Q92508" }, "relationship_type": "causal", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Stabilin-1 is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "Stabilin-1 mediates efferocytosis of oxidized lipids; its absence aggravates fibrosis and delays resolution.", "protein": "Stabilin-1", "relationship_type": "protective", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Steatosis", "glycan_involvement": "Tim4 is glycosylated; glycosylation may affect receptor function.", "mechanism": "Tim4 synergizes with TAM receptors for efferocytosis; absence leads to increased inflammation and severe steatosis.", "protein": "Tim4", "relationship_type": "protective", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "MerTK is glycosylated; glycosylation may affect receptor function.", "mechanism": "MerTK (TAM receptor) mediates efferocytosis, limiting inflammation and fibrosis.", "protein": "MerTK", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological proce", "gene_name": "MERTK", "glycan_count": 28, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G62461SM", "G10486CT", "G11629QQ", "G37399XV", "G59626AS", "G65184UU", "G80920RR", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G56784JY", "G57888GL", "G62765YT", "G02815KT", "G23010ZW", "G02030ZB", "G10019LZ", "G12580WI", "G15169WU", "G22310AV", "G38663NM", "G52527GH", "G83460ZZ", "G84452RH", "G06356OH", "G29068FM", "G43417UB" ], "uniprot_id": "Q12866" }, "relationship_type": "protective", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Bile duct ligation-induced fibrosis", "glycan_involvement": "Integrins are glycoproteins; glycosylation affects ligand binding and signaling.", "mechanism": "Integrin \u03b1v\u03b23 mediates efferocytosis and inhibits pro-inflammatory cytokine production, limiting fibrosis.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Collagens are glycoproteins; glycosylation affects ECM structure.", "mechanism": "COL1A1 expression correlates with Piezo1 and fibrosis severity.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC11152137" }, { "confidence": "medium", "disease": "Lung injury/fibrosis", "glycan_involvement": "TGF-\u03b21 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Efferocytosis by macrophages induces TGF-\u03b21 production, promoting fibrosis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC11152137" }, { "confidence": "high", "disease": "Hepatitis A", "glycan_involvement": "IgM is heavily glycosylated, affecting stability and immune recognition", "mechanism": "IgM antibody indicates acute HAV infection", "protein": "Hepatitis A Virus IgM Antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "Myoglobin is glycosylated, influencing renal filtration and toxicity", "mechanism": "Myoglobin released from damaged muscle; detected in urine (myoglobinuria)", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation affects enzyme stability and serum half-life", "mechanism": "Elevated AST reflects muscle and liver injury", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation modulates enzyme activity", "mechanism": "ALT elevation may occur due to muscle breakdown", "protein": "Alanine Transaminase (ALT)", "protein_enriched": { "function": "Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule", "gene_name": "rub", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24297" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation influences LDH stability and clearance", "mechanism": "LDH is released from damaged muscle cells", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation affects enzyme secretion and detection", "mechanism": "Elevated aldolase indicates muscle injury", "protein": "Aldolase", "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Acute Kidney Injury", "glycan_involvement": "Glycosylation may affect renal handling of myoglobin", "mechanism": "Myoglobinuria leads to renal tubular toxicity and AKI", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "causal", "source_pmcid": "PMC11152228" }, { "confidence": "low", "disease": "Rhabdomyolysis", "glycan_involvement": "IgM glycosylation modulates immune response", "mechanism": "HAV infection triggers immune-mediated muscle injury", "protein": "Hepatitis A Virus IgM Antibody", "relationship_type": "causal", "source_pmcid": "PMC11152228" }, { "confidence": "low", "disease": "Polymyositis", "glycan_involvement": "Glycosylation impacts myoglobin immunogenicity", "mechanism": "Elevated myoglobin may reflect inflammatory myopathy", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "Glycosylation affects AST serum levels", "mechanism": "AST elevation is a marker of hepatic injury in HAV", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152228" }, { "confidence": "high", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Glycosylation affects C1q stability and immune complex binding", "mechanism": "Immune complex deposition in glomeruli", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "high", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "Glycosylation modulates complement activation", "mechanism": "Complement activation and deposition in renal tissue", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Fc glycosylation regulates effector function and autoimmunity", "mechanism": "Polyclonal increase and immune complex formation", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "medium", "disease": "Proliferative glomerulonephritis", "glycan_involvement": "O-glycosylation affects IgA deposition and clearance", "mechanism": "Immune deposits in glomeruli", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation influences autoantibody pathogenicity", "mechanism": "Autoantibody presence associated with SLE", "protein": "Anti-cardiolipin IgG", "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates antibody affinity and immune complex formation", "mechanism": "Autoantibody against DNA, diagnostic for SLE", "protein": "Anti-native DNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for CRP function", "mechanism": "Elevated in inflammatory syndrome", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152231" }, { "confidence": "medium", "disease": "Autoimmune myelofibrosis (AIMF)", "glycan_involvement": "N-glycosylation required for PDGF receptor binding", "mechanism": "Stimulates fibroblasts, leading to marrow fibrosis", "protein": "PDGF", "relationship_type": "causal", "source_pmcid": "PMC11152231" }, { "confidence": "medium", "disease": "Autoimmune myelofibrosis (AIMF)", "glycan_involvement": "Glycosylation affects TGF\u03b2 secretion and activity", "mechanism": "Promotes fibroblast activation and collagen production", "protein": "TGF\u03b2", "relationship_type": "causal", "source_pmcid": "PMC11152231" }, { "confidence": "low", "disease": "Autoimmune myelofibrosis (AIMF)", "glycan_involvement": "Glycosylation modulates EGF receptor interaction", "mechanism": "Stimulates fibroblast proliferation", "protein": "EGF", "relationship_type": "causal", "source_pmcid": "PMC11152231" }, { "confidence": "high", "disease": "Khat-induced Autoimmune Hepatitis", "glycan_involvement": "IgG is a glycoprotein; altered glycosylation may modulate immune activity, but not specifically discussed.", "mechanism": "Elevated serum IgG is a hallmark of autoimmune hepatitis and was observed in all khat-induced AIH cases.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Khat-induced Autoimmune Hepatitis", "glycan_involvement": "ANA are autoantibodies (glycoproteins); glycosylation may affect antigen recognition.", "mechanism": "Positive ANA is used to diagnose AIH and was present in some khat-induced cases.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Khat-induced Autoimmune Hepatitis", "glycan_involvement": "ASMA are autoantibodies (glycoproteins); glycosylation may affect immune complex formation.", "mechanism": "ASMA positivity supports AIH diagnosis and was found in some khat-induced cases.", "protein": "Anti-Smooth Muscle Antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "IgG glycosylation patterns can influence immune response and disease activity.", "mechanism": "Elevated IgG is a diagnostic marker for AIH.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "Glycosylation may affect ANA antigen binding.", "mechanism": "ANA positivity is a diagnostic criterion for AIH.", "protein": "Antinuclear Antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "Glycosylation may affect ASMA function.", "mechanism": "ASMA is a diagnostic marker for AIH.", "protein": "Anti-Smooth Muscle Antibody (ASMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "IgG glycosylation can modulate inflammatory responses.", "mechanism": "Elevated IgG may indicate immune-mediated liver injury.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152234" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation affects receptor function and drug binding.", "mechanism": "Inhibition of platelet aggregation via glycoprotein IIb/IIIa reduces thrombus formation during PCI in AMI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152258" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation may influence stability and detection in assays.", "mechanism": "Elevated serum cardiac troponin I is used to diagnose AMI.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152258" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation modulates receptor expression and drug response.", "mechanism": "P2Y12 inhibitors prevent platelet activation, reducing risk of recurrent events post-PCI.", "protein": "P2Y12 Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152258" }, { "confidence": "medium", "disease": "Target Vessel Myocardial Infarction", "glycan_involvement": "Glycosylation impacts ligand binding and inhibitor efficacy.", "mechanism": "Use of glycoprotein IIb/IIIa inhibitors during PCI lowers incidence of target vessel MI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152258" }, { "confidence": "medium", "disease": "Cardiac Death", "glycan_involvement": "Glycosylation may affect receptor turnover and function.", "mechanism": "Inhibition during PCI is associated with reduced cardiac death rates.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "protective", "source_pmcid": "PMC11152258" }, { "confidence": "medium", "disease": "Target Vessel Myocardial Infarction", "glycan_involvement": "Glycosylation influences receptor pharmacodynamics.", "mechanism": "P2Y12 inhibition reduces risk of target vessel MI after stenting.", "protein": "P2Y12 Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152258" }, { "confidence": "medium", "disease": "Target Vessel Myocardial Infarction", "glycan_involvement": "Glycosylation may affect immunoassay sensitivity.", "mechanism": "Troponin I elevation indicates myocardial necrosis in target vessel MI.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152258" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation affects receptor stability and expression.", "mechanism": "A2AR overexpression promotes immunosuppression and tumor immune escape; blockade restores antitumor immunity.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation may regulate receptor surface expression.", "mechanism": "High A2AR expression correlates with advanced stage, metastasis, and poor prognosis.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "biomarker", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may modulate receptor function.", "mechanism": "A2AR activation increases proliferation and invasion.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Likely N-glycosylation involvement in receptor trafficking.", "mechanism": "A2AR and A2BR upregulation promotes tumor proliferation.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect receptor signaling.", "mechanism": "A2AR activation inhibits NF-\u03baB and pro-inflammatory cytokines, increases IL-10, contributing to immune dysregulation.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may regulate receptor activity.", "mechanism": "A2AR activation suppresses inflammatory cytokines, promoting disease.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may influence receptor function.", "mechanism": "A2AR activation increases anti-inflammatory cytokines, contributing to autoimmune pathology.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation may affect receptor pharmacology.", "mechanism": "A2AR antagonists show efficacy in clinical trials for symptom management.", "protein": "Adenosine A2A receptor (A2AR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152298" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation required for enzymatic activity and cell surface localization.", "mechanism": "Upregulation in tumors converts ATP to adenosine, promoting immunosuppression.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation essential for function and stability.", "mechanism": "Upregulation in tumors increases adenosine production, facilitating immune escape.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC11152298" }, { "confidence": "high", "disease": "Mitral regurgitation", "glycan_involvement": "VWF glycosylation is essential for multimer formation and function.", "mechanism": "MR causes high shear stress, leading to excessive cleavage and loss of VWF large multimers.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Acquired von Willebrand syndrome", "glycan_involvement": "Glycosylation maintains VWF multimer stability and hemostatic function.", "mechanism": "Loss of VWF large multimers due to shear stress in MR/AS leads to AVWS.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Aortic stenosis", "glycan_involvement": "Glycosylation required for VWF multimerization and susceptibility to cleavage.", "mechanism": "AS induces high shear stress, causing loss of VWF large multimers and AVWS.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Gastrointestinal bleeding", "glycan_involvement": "Glycosylation affects VWF interaction with platelets and vessel wall.", "mechanism": "Loss of VWF large multimers impairs hemostasis, increasing GI bleeding risk, especially in AS.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "medium", "disease": "Angiodysplasia", "glycan_involvement": "Glycosylation influences VWF adhesive properties.", "mechanism": "Loss of VWF large multimers is associated with bleeding from angiodysplasia, especially in AS.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation required for VWF function in hemostasis.", "mechanism": "Chronic GI bleeding due to loss of VWF large multimers leads to anemia, more frequent in AS than MR.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Mitral regurgitation", "glycan_involvement": "Glycosylation status affects VWF-LMI measurement.", "mechanism": "VWF large multimer index (VWF-LMI) is reduced in MR and reflects disease severity.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Acquired von Willebrand syndrome", "glycan_involvement": "Glycosylation impacts VWF activity and antigenicity.", "mechanism": "VWF:RCo/VWF:Ag ratio and VWF-LMI are diagnostic markers for AVWS in MR/AS.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "Mitral regurgitation", "glycan_involvement": "Restoration of VWF multimers depends on glycosylation-mediated multimer assembly.", "mechanism": "Mitral valve intervention restores VWF large multimers and improves hemostatic parameters.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152679" }, { "confidence": "medium", "disease": "Angiodysplasia", "glycan_involvement": "Glycosylation maintains VWF function but is not sufficient alone to cause angiodysplasia.", "mechanism": "Preserved hemodynamics in MR may protect against angiodysplasia despite VWF multimer loss.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11152679" }, { "confidence": "high", "disease": "HFRS", "glycan_involvement": "TIM-1 is a mucin-type glycoprotein; its glycosylated extracellular domain may mediate virus binding and entry.", "mechanism": "TIM-1 acts as a critical entry receptor for Hantaan virus (HTNV) in human CD4+ T cells, facilitating viral infection and replication, which contributes to HFRS pathogenesis.", "protein": "TIM-1", "relationship_type": "causal", "source_pmcid": "PMC11152704" }, { "confidence": "high", "disease": "HFRS", "glycan_involvement": "Glycosylation of TIM-1 may affect antibody accessibility and receptor function.", "mechanism": "Blocking TIM-1 with specific antibodies or shRNA reduces HTNV infection in T cells, suggesting TIM-1 as a potential antiviral target.", "protein": "TIM-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152704" }, { "confidence": "medium", "disease": "HFRS", "glycan_involvement": "Glycosylation status may influence TIM-1 surface expression and detection.", "mechanism": "Surface expression level of TIM-1 on T cells correlates with susceptibility to HTNV infection.", "protein": "TIM-1", "relationship_type": "biomarker", "source_pmcid": "PMC11152704" }, { "confidence": "high", "disease": "HFRS", "glycan_involvement": "Mucin-type O-glycosylation may increase receptor density and viral binding.", "mechanism": "Overexpression of TIM-1 in Jurkat T cells markedly enhances HTNV infection and replication.", "protein": "TIM-1", "relationship_type": "causal", "source_pmcid": "PMC11152704" }, { "confidence": "high", "disease": "HFRS", "glycan_involvement": "Reduced glycosylated TIM-1 limits viral attachment.", "mechanism": "Knockdown of TIM-1 in T cells substantially decreases HTNV infection, indicating protective effect against viral entry.", "protein": "TIM-1", "relationship_type": "protective", "source_pmcid": "PMC11152704" }, { "confidence": "medium", "disease": "HFRS", "glycan_involvement": "Glycosylation may facilitate endocytic uptake and receptor clustering.", "mechanism": "TIM-1 mediates HTNV entry via clathrin-dependent endocytosis in T cells, promoting systemic viral dissemination.", "protein": "TIM-1", "relationship_type": "causal", "source_pmcid": "PMC11152704" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects EpCAM stability and cell surface expression.", "mechanism": "EpCAM is overexpressed in CRC cells and serves as a carcinoma marker.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152836" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may regulate Cyclin D1 stability and function.", "mechanism": "Lactococcus lactis and nisin reduce Cyclin D1 expression, inhibiting CRC cell proliferation.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152836" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation modulates TRAIL receptor binding and apoptotic signaling.", "mechanism": "Recombinant Lactococcus lactis expressing TRAIL induces apoptosis in CRC cell lines.", "protein": "TRAIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152836" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation required for IL-6 secretion and activity.", "mechanism": "IL-6 overproduction promotes CRC via STAT3/NF-\u03baB activation; L. lactis reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11152836" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation necessary for IL-8 function.", "mechanism": "IL-8 promotes CRC cell growth; L. lactis reduces IL-8 secretion.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "causal", "source_pmcid": "PMC11152836" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation required for IL-18 maturation and secretion.", "mechanism": "IL-18 released by inflammasome activation triggers CRC development.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal", "source_pmcid": "PMC11152836" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interaction.", "mechanism": "TNF-\u03b1 overproduction in CRC lesions promotes inflammation and tumorigenesis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11152836" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may influence Bcl-2 localization and function.", "mechanism": "L. lactis expressing TRAIL decreases Bcl-2 expression, promoting CRC cell apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152836" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect Bax activity.", "mechanism": "L. lactis expressing TRAIL increases Bax expression, inducing apoptosis in CRC cells.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152836" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation modulates HER2 receptor function and antibody binding.", "mechanism": "HER2-targeting by engineered L. lactis enables tumor antigen recognition for CRC theranostics.", "protein": "HER2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11152836" }, { "confidence": "high", "disease": "Heyde syndrome", "glycan_involvement": "vWF is a heavily glycosylated plasma protein; glycosylation affects its multimerization and function.", "mechanism": "Loss of high-molecular-weight vWF multimers due to shear stress in AS leads to acquired vWF deficiency and bleeding.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11152847" }, { "confidence": "medium", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "Activated platelets expressing GPIIb/IIIa contribute to thrombotic complications in CAVD; targeted by PET tracer 18F-GP1.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "biomarker", "source_pmcid": "PMC11152847" }, { "confidence": "high", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "Lp(a) contains heavily glycosylated apolipoprotein(a); glycosylation affects plasma levels and pathogenicity.", "mechanism": "Elevated Lp(a) promotes lipid deposition, inflammation, and calcification in aortic valve; lowering Lp(a) slows CAVD progression.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11152847" }, { "confidence": "high", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "Fetuin-A is N- and O-glycosylated, which is essential for its solubility and calcification inhibition.", "mechanism": "Fetuin-A inhibits ectopic calcification by forming soluble protein-mineral complexes; low levels predict CAVD progression.", "protein": "Fetuin-A", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11152847" }, { "confidence": "medium", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "MGP is a secreted glycoprotein; glycosylation may affect secretion and function.", "mechanism": "MGP inhibits vascular and valvular calcification; deficiency or antagonism (e.g., by vitamin K antagonists) accelerates CAVD.", "protein": "Matrix Gla protein", "relationship_type": "protective", "source_pmcid": "PMC11152847" }, { "confidence": "medium", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and receptor interactions.", "mechanism": "IL-6 promotes valve mineralization and inflammation; specific SNPs increase risk.", "protein": "Interleukin-6", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11152847" }, { "confidence": "high", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "NOTCH1 is O-fucosylated and O-glucosylated; glycosylation modulates ligand binding and signaling.", "mechanism": "NOTCH1 mutations drive osteogenic differentiation of VICs and valve calcification.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11152847" }, { "confidence": "medium", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "PCSK9 is N-glycosylated, which affects secretion and activity.", "mechanism": "PCSK9 inhibitors lower Lp(a) and LDL, slowing CAVD progression.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11152847" }, { "confidence": "medium", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "Biglycan is a proteoglycan with glycosaminoglycan chains; glycosylation is essential for its function.", "mechanism": "Biglycan-TLR3-IFNAR1 axis regulates AV calcification via inflammation.", "protein": "Biglycan", "relationship_type": "causal", "source_pmcid": "PMC11152847" }, { "confidence": "low", "disease": "Calcific aortic valve disease (CAVD)", "glycan_involvement": "NAV1 is predicted to be glycosylated; glycosylation may affect cell adhesion properties.", "mechanism": "NAV1 expression is associated with genetic risk loci for CAVD and vascular function.", "protein": "NAV1", "protein_enriched": { "function": "Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs", "gene_name": "NAV2", "glycan_count": 18, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02030ZB", "G08293MJ", "G10019LZ", "G12580WI", "G25418HZ", "G52527GH", "G84452RH", "G57888GL", "G11629QQ", "G55412XP", "G56784JY", "G49108TO", "G22310AV", "G59536GA", "G37881RL", "G69878NJ", "G05049YU", "G39595FH" ], "uniprot_id": "Q8IVL1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11152847" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation of the glycoprotein precursor is critical for proper folding, viral infectivity, and immune evasion.", "mechanism": "The CCHFV glycoprotein precursor is essential for viral entry, assembly, and infectivity, mediating host cell attachment and membrane fusion.", "protein": "CCHFV glycoprotein precursor", "relationship_type": "causal", "source_pmcid": "PMC11152863" }, { "confidence": "high", "disease": "Ventricular Septal Defect with Pulmonary Arterial Hypertension (VSD with PAH)", "glycan_involvement": "NTproBNP is a glycoprotein; glycosylation affects its stability and detection as a biomarker.", "mechanism": "NTproBNP levels are elevated in VSD with PAH and considered a risk factor for disease progression.", "protein": "pro-brain natriuretic peptide (NTproBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC11154966" }, { "confidence": "high", "disease": "Late-onset Alzheimer\u2019s Disease (LOAD)", "glycan_involvement": "APOE is a glycoprotein; glycosylation may modulate its function and aggregation propensity.", "mechanism": "APOE \u03b54 allele increases vulnerability to LOAD; genotype correlates with brain structure and connectivity changes.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/risk factor", "source_pmcid": "PMC11154966" }, { "confidence": "high", "disease": "SHH Medulloblastoma", "glycan_involvement": "SHH is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "Aberrant SHH signaling drives tumorigenesis in SHH-MB.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "causal", "source_pmcid": "PMC11183748" }, { "confidence": "high", "disease": "Metastatic Infant Medulloblastoma", "glycan_involvement": "Glycosylation modulates SHH function and tumor behavior.", "mechanism": "SHH subgroup identification predicts superior survival and therapy response.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "SHH Medulloblastoma (SHH\u00df and SHH\u03b3 subtypes)", "glycan_involvement": "Potential differential glycosylation may affect subtype behavior.", "mechanism": "SHH\u00df and SHH\u03b3 subtypes both respond well to intensified chemotherapy.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "high", "disease": "Group 3 Medulloblastoma", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MYC amplification is associated with poor prognosis.", "protein": "MYC", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "Group 3 Medulloblastoma", "glycan_involvement": "Glycosylation of SHH may contribute to its protective effect.", "mechanism": "SHH-MB patients have superior survival compared to Group 3-MB.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "protective", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "Group 4 Medulloblastoma", "glycan_involvement": "Glycosylation may influence SHH activity and outcomes.", "mechanism": "SHH-MB patients fare better than Group 4-MB.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "protective", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "Metastatic Infant Medulloblastoma", "glycan_involvement": "Glycosylation status may affect drug targeting.", "mechanism": "SHH pathway is a target for intensified therapy in SHH-MB.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183748" }, { "confidence": "low", "disease": "Metastatic Infant Medulloblastoma", "glycan_involvement": "Glycosylation may affect SHH-mediated cell migration.", "mechanism": "SHH-MB patients have more local than metastatic relapses.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "high", "disease": "Metastatic Infant Medulloblastoma", "glycan_involvement": "No glycosylation involvement.", "mechanism": "MYC amplification portends near uniformly fatal prognosis.", "protein": "MYC", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "SHH Medulloblastoma", "glycan_involvement": "Glycosylation may influence SHH stability and signaling.", "mechanism": "Non-radiated SHH-MB patients have superior 5-year PFS compared to other subgroups.", "protein": "SHH (Sonic Hedgehog)", "relationship_type": "biomarker", "source_pmcid": "PMC11183748" }, { "confidence": "medium", "disease": "Medulloblastoma", "glycan_involvement": "Implied; glycoprotein modifications may drive subgroup-specific signaling and tumor microenvironment interactions.", "mechanism": "Proteomics revealed subgroup-specific glycoprotein expression patterns correlating with disease heterogeneity and potential therapeutic vulnerabilities.", "protein": "Unspecified glycoproteins (subgroup-specific)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11183846" }, { "confidence": "medium", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Likely glycosylated as a membrane transporter, glycosylation may affect trafficking and function.", "mechanism": "Upregulated in response to DFMO, mediates compensatory polyamine uptake.", "protein": "Polyamine Transporter", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183965" }, { "confidence": "high", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Drives polyamine synthesis; increased expression correlates with tumor stemness, cell cycle, hypoxia, and angiogenesis.", "protein": "ODC1 (Ornithine Decarboxylase 1)", "protein_enriched": { "function": "Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essenti", "gene_name": "ODC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11926" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "Diffuse Midline Glioma (DMG)", "glycan_involvement": "Glycosylation may regulate transporter stability and surface expression.", "mechanism": "DMG cells depend on polyamine uptake; inhibition suppresses tumor growth.", "protein": "Polyamine Transporter", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "High-grade Glioma", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "ODC1 expression correlates with functional tumor states.", "protein": "ODC1 (Ornithine Decarboxylase 1)", "protein_enriched": { "function": "Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essenti", "gene_name": "ODC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Annexin V is a glycoprotein; glycosylation may affect its binding properties.", "mechanism": "Annexin V staining used to detect apoptosis induced by dual polyamine inhibition.", "protein": "Annexin V", "relationship_type": "biomarker", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Glycosylation may modulate transporter activity.", "mechanism": "Compensatory upregulation supports tumor survival under DFMO treatment.", "protein": "Polyamine Transporter", "relationship_type": "causal", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "ODC1 upregulation upon AMXT1501 treatment supports polyamine synthesis and tumor growth.", "protein": "ODC1 (Ornithine Decarboxylase 1)", "protein_enriched": { "function": "Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essenti", "gene_name": "ODC1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11926" }, "relationship_type": "causal", "source_pmcid": "PMC11183965" }, { "confidence": "high", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Not glycosylated.", "mechanism": "Cells sensitized to topoisomerase-I inhibitor SN-38 by dual polyamine pathway inhibition.", "protein": "Topoisomerase I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183965" }, { "confidence": "high", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Glycosylation may influence drug sensitivity.", "mechanism": "Dual inhibition (DFMO + AMXT1501) synergistically suppresses proliferation and colony formation.", "protein": "Polyamine Transporter", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11183965" }, { "confidence": "medium", "disease": "Medulloblastoma (Group-3)", "glycan_involvement": "Glycosylation may affect detection and quantification.", "mechanism": "Elevated transporter expression marks compensatory response to polyamine synthesis inhibition.", "protein": "Polyamine Transporter", "relationship_type": "biomarker", "source_pmcid": "PMC11183965" }, { "confidence": "high", "disease": "Medulloblastoma", "glycan_involvement": "not described", "mechanism": "WEE1 is upregulated in all MB subtypes and is critical for MB cell viability.", "protein": "WEE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11184104" }, { "confidence": "high", "disease": "Group 3 Medulloblastoma", "glycan_involvement": "not described", "mechanism": "Myc-driven MB is sensitive to WEE1 inhibition by AZD1775.", "protein": "WEE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11184104" }, { "confidence": "high", "disease": "Group 3 Medulloblastoma", "glycan_involvement": "not described", "mechanism": "CDK7 mediates resistance to WEE1 inhibitor AZD1775; inhibition of CDK7 restores sensitivity.", "protein": "CDK7", "protein_enriched": { "function": "Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). Cyclin-dependent kinases", "gene_name": "CDK7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50613" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11184104" }, { "confidence": "high", "disease": "Medulloblastoma", "glycan_involvement": "not described", "mechanism": "CDK7 controls transcriptional initiation and is implicated in resistance mechanisms.", "protein": "CDK7", "protein_enriched": { "function": "Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). Cyclin-dependent kinases", "gene_name": "CDK7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50613" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11184104" }, { "confidence": "high", "disease": "Group 3 Medulloblastoma", "glycan_involvement": "not described", "mechanism": "MYC amplification is associated with poor prognosis, metastasis, and recurrence.", "protein": "MYC", "relationship_type": "causal", "source_pmcid": "PMC11184104" }, { "confidence": "medium", "disease": "Medulloblastoma", "glycan_involvement": "not described", "mechanism": "CDK7 phosphorylates RNA Pol II, promoting transcription of resistance genes.", "protein": "RNA Pol II", "protein_enriched": { "function": "Catalytic core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates", "gene_name": "POLR2A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P24928" }, "relationship_type": "causal", "source_pmcid": "PMC11184104" }, { "confidence": "medium", "disease": "Kounis syndrome", "glycan_involvement": "Heavily glycosylated spike protein may enhance immunogenicity and allergenicity.", "mechanism": "Spike glycoprotein in vaccines can trigger immune/allergic responses leading to coronary vasospasm and thrombosis.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC11188795" }, { "confidence": "medium", "disease": "Anaphylaxis", "glycan_involvement": "Glycans on spike protein can be recognized by immune system, contributing to hypersensitivity.", "mechanism": "Spike glycoprotein or its glycan structures may act as allergens, triggering systemic allergic reactions.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC11188795" }, { "confidence": "high", "disease": "Kounis syndrome", "glycan_involvement": "Glycosylation affects receptor function and platelet aggregation.", "mechanism": "Inhibitors (eptifibatide) used to treat thrombosis in Kounis syndrome.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11188795" }, { "confidence": "high", "disease": "Kounis syndrome", "glycan_involvement": "IgE is a glycoprotein; glycosylation modulates receptor binding and immune activation.", "mechanism": "IgE-mediated mast cell activation releases mediators causing coronary events.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11188795" }, { "confidence": "high", "disease": "Anaphylaxis", "glycan_involvement": "Glycosylation critical for IgE stability and function.", "mechanism": "IgE cross-linking on mast cells triggers systemic allergic reactions.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11188795" }, { "confidence": "medium", "disease": "Acute coronary syndrome", "glycan_involvement": "Glycans may modulate immune recognition and inflammatory response.", "mechanism": "Immune response to spike glycoprotein can induce coronary inflammation and thrombosis.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC11188795" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ligand binding and cell surface expression.", "mechanism": "VCAM-1 is upregulated on activated endothelial cells, mediates monocyte adhesion and recruitment to plaques; targeting VCAM-1 improves drug delivery to inflamed endothelium.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "ICAM-1 is upregulated in response to inflammation, facilitates monocyte trans-endothelial migration; antibody targeting enables imaging and drug delivery.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation critical for ligand recognition (sialyl Lewis X).", "mechanism": "E-selectin is induced on activated endothelium, mediates leukocyte rolling; ligand-modified nanoparticles target E-selectin for drug delivery.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for PSGL-1 binding.", "mechanism": "P-selectin promotes platelet-leukocyte aggregation and monocyte recruitment; targeting P-selectin inhibits inflammation and plaque progression.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences receptor function and ligand binding.", "mechanism": "CD36 mediates uptake of oxidized LDL by macrophages, leading to foam cell formation and plaque development.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation and sulfation modulate HA binding affinity.", "mechanism": "CD44 is upregulated in plaques, binds hyaluronic acid; targeting CD44 enables nanoparticle delivery to plaque macrophages.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation and sialylation essential for selectin binding.", "mechanism": "PSGL-1 on monocytes binds P- and E-selectin, mediating rolling and recruitment to plaques.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC11189587" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ligand binding and receptor stability.", "mechanism": "SR-A is overexpressed on plaque macrophages, mediates ox-LDL uptake; targeting SR-A inhibits foam cell formation.", "protein": "SR-A (MSR1)", "protein_enriched": { "function": "Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a", "gene_name": "MSR1", "glycan_count": 10, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G05962QB", "G09831WQ", "G32788FZ", "G35541EV", "G62765YT", "G80479JV", "G93718GY", "G92050GC", "G92275SC", "G99679NM" ], "uniprot_id": "P21757" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11189587" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect cell surface localization.", "mechanism": "CD9 is upregulated in atherosclerotic lesions, regulates cell migration and adhesion; targeting CD9 enables drug delivery to plaques.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11189587" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Phosphorylation and glycosylation modulate function and cell interactions.", "mechanism": "OPN is highly expressed in VSMCs and foam cells, marks phenotypic transition and inflammation in plaques.", "protein": "Osteopontin (OPN)", "relationship_type": "biomarker", "source_pmcid": "PMC11189587" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Potential glycosylation may affect stability and localization, but not directly discussed.", "mechanism": "Upregulated in HCC, promotes cell cycle progression and tumorigenesis; associated with poor prognosis.", "protein": "AURKA", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Potential glycosylation may regulate cell cycle function, but not directly discussed.", "mechanism": "Upregulated in HCC, regulates G2/M checkpoint, promotes proliferation and migration; associated with poor prognosis.", "protein": "CCNB2", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G2/M (mitosis) transition", "gene_name": "CCNB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95067" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "F9 is a glycoprotein; glycosylation is essential for secretion and function.", "mechanism": "Downregulated in HCC; loss impairs senescence and apoptosis, facilitating tumor growth.", "protein": "F9", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CYP2E1 is glycosylated; glycosylation affects enzyme activity and stability.", "mechanism": "Downregulated in HCC; low expression promotes malignant phenotype and tumor progression.", "protein": "CYP2E1", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11192999" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Potential glycosylation may affect metabolic activity.", "mechanism": "Upregulated in MSG-induced liver damage; promotes glycolysis, tumor growth, and metastasis.", "protein": "ALDOA", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also ", "gene_name": "ALDOA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04075" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11192999" }, { "confidence": "medium", "disease": "Apoptosis", "glycan_involvement": "Potential glycosylation may regulate activation.", "mechanism": "Upregulated in MSG-induced liver damage; marker of apoptosis.", "protein": "CASP3", "relationship_type": "biomarker", "source_pmcid": "PMC11192999" }, { "confidence": "medium", "disease": "Apoptosis", "glycan_involvement": "Potential glycosylation may regulate activation.", "mechanism": "Upregulated in MSG-induced liver damage; marker of apoptosis.", "protein": "CASP9", "relationship_type": "biomarker", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Senescence", "glycan_involvement": "Glycosylation required for F9 function in plasma.", "mechanism": "Upregulation induces senescence, halting malignant transformation; downregulation blocks senescence.", "protein": "F9", "relationship_type": "causal/protective", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Liver damage", "glycan_involvement": "Glycosylation affects CYP2E1 stability and activity.", "mechanism": "Downregulation by MSG exposure impairs xenobiotic metabolism, increasing susceptibility to damage.", "protein": "CYP2E1", "relationship_type": "causal/protective", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Potential glycosylation may modulate kinase activity.", "mechanism": "Overexpression drives cell cycle dysregulation and metastasis.", "protein": "AURKA", "relationship_type": "causal", "source_pmcid": "PMC11192999" }, { "confidence": "high", "disease": "Coronary Microvascular Dysfunction (CMD)", "glycan_involvement": "Glycosylation critical for secretion and stability; glycan-dependent immune modulation.", "mechanism": "Marker of inflammation and tissue remodeling; elevated in CMD.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "N-glycosylation affects peptide processing and plasma half-life.", "mechanism": "Elevated in ventricular remodeling and cardiac stress; associated with impaired CFVR.", "protein": "BNP (Brain Natriuretic Peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "N-glycosylation modulates immunoreactivity and clearance.", "mechanism": "Reflects cardiac remodeling and dysfunction; increased in CMD.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "Key regulator of blood pressure; elevated in CMD, hypertension, and cardiac remodeling.", "protein": "REN (Renin)", "protein_enriched": { "function": "Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of bloo", "gene_name": "REN", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04689DA", "G05724UK", "G06110VR", "G12932QT", "G14669DU", "G14889BN", "G15956KF", "G16828VN", "G18938DW", "G20425TQ", "G22768VO", "G23863VK", "G23869AA", "G29857RC", "G36191CD", "G39188ZX", "G45359RY", "G47012YE", "G50045TK", "G55220VL", "G63889NK", "G64527OM", "G67381VP", "G72735IY", "G72797UR", "G74724QE", "G78059CC", "G79809MM", "G82348BZ", "G86357DX", "G90093AU", "G93180LE" ], "uniprot_id": "P00797" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "O-glycosylation influences peptide stability and receptor interaction.", "mechanism": "Vasodilator and angiogenic peptide; increased in CMD and heart failure.", "protein": "ADM (Adrenomedullin)", "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "N-glycosylation modulates secretion and bioactivity.", "mechanism": "Upregulated in inflammation, aging, and metabolic stress; associated with impaired CFVR.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "CMD", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Driver of vascular inflammation; strongly associated with impaired CFVR.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11198373" }, { "confidence": "medium", "disease": "CMD", "glycan_involvement": "N-glycosylation modulates receptor function and ligand binding.", "mechanism": "Receptor for apoptotic signaling; associated with adverse CVD outcomes and CMD.", "protein": "TRAILR2", "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "medium", "disease": "CMD", "glycan_involvement": "Potential N-glycosylation may affect protease activity.", "mechanism": "Serine protease linked to vascular remodeling; associated with impaired CFVR.", "protein": "PRSS27", "protein_enriched": { "function": "", "gene_name": "C11orf68", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H3H3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "medium", "disease": "CMD", "glycan_involvement": "N-glycosylation required for secretion and anti-inflammatory activity.", "mechanism": "Adipokine involved in vascular function and inflammation; associated with CMD.", "protein": "SERPINA12 (Vaspin)", "protein_enriched": { "function": "Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues", "gene_name": "SERPINA12", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8IW75" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198373" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Lp(a) contains heavily glycosylated apo(a) with kringle IV domains; glycosylation affects isoform size and plasma levels.", "mechanism": "Elevated Lp(a) levels increase risk of coronary events in statin-treated stroke/TIA survivors.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation of apo(a) influences isoform size and Lp(a) concentration.", "mechanism": "Short apo(a) isoforms (fewer kringle IV domains) are associated with increased CAD risk in statin-treated stroke/TIA survivors.", "protein": "Apolipoprotein(a)", "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation status not directly linked to stroke recurrence in this cohort.", "mechanism": "No significant association between Lp(a) levels and recurrent stroke risk in secondary prevention.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation not implicated in stroke recurrence.", "mechanism": "No significant association between apo(a) isoform size and recurrent stroke risk.", "protein": "Apolipoprotein(a)", "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "medium", "disease": "Peripheral artery disease", "glycan_involvement": "Glycosylation not implicated in peripheral events.", "mechanism": "No significant association between Lp(a) levels and peripheral vascular events in this cohort.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "medium", "disease": "Peripheral artery disease", "glycan_involvement": "Glycosylation not implicated in peripheral events.", "mechanism": "No significant association between apo(a) isoform size and peripheral vascular events.", "protein": "Apolipoprotein(a)", "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "medium", "disease": "Large artery atherosclerotic stroke", "glycan_involvement": "Glycosylation of apo(a) affects Lp(a) levels and isoform size, potentially influencing risk.", "mechanism": "Elevated Lp(a) may increase risk of large artery atherosclerotic stroke (suggested by subgroup analysis and literature).", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "low", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "ApoB100 is glycosylated; glycan status may affect lipoprotein function.", "mechanism": "OxPL-apoB (oxidized phospholipids on apoB100) previously reported to predict CAD risk, but not confirmed in this study.", "protein": "Apolipoprotein B100", "relationship_type": "biomarker", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Therapies target apo(a) synthesis, affecting glycosylation and Lp(a) plasma levels.", "mechanism": "Lowering Lp(a) (via PCSK9i, antisense, siRNA) may reduce residual CAD risk in statin-treated stroke/TIA survivors.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Reduced apo(a) synthesis alters glycosylation profile and lowers Lp(a) levels.", "mechanism": "Antisense and siRNA therapies targeting apo(a) production reduce Lp(a) and CAD risk.", "protein": "Apolipoprotein(a)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198425" }, { "confidence": "high", "disease": "Worsening renal function", "glycan_involvement": "Glycosylation essential for P-glycoprotein trafficking and function.", "mechanism": "P-glycoprotein modulates renal clearance of edoxaban; inhibitors require dose adjustment to prevent renal decline.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198551" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Indirect; edoxaban transport depends on glycosylated P-glycoprotein.", "mechanism": "Edoxaban prevents stroke and bleeding in AF; dosing affected by renal function and P-glycoprotein activity.", "protein": "Edoxaban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Major bleeding", "glycan_involvement": "N-glycosylation modulates albumin stability and function.", "mechanism": "Albumin levels may affect drug binding and bleeding risk in anticoagulated patients.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Worsening renal function", "glycan_involvement": "Altered glycosylation in renal disease.", "mechanism": "Transferrin glycoforms may reflect renal dysfunction and inflammation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Fc glycosylation affects immune response.", "mechanism": "IgG glycoforms may modulate inflammation and risk of stroke in AF.", "protein": "Immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "high", "disease": "Major bleeding", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "P-glycoprotein inhibitors increase edoxaban exposure, raising bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Worsening renal function", "glycan_involvement": "N-glycosylation impacts albumin half-life.", "mechanism": "Low albumin may indicate renal dysfunction and poor drug binding.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation changes in diabetes.", "mechanism": "Transferrin glycoforms altered in diabetes, may reflect metabolic control.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Fc glycosylation modulates immune activity.", "mechanism": "IgG glycosylation patterns may be altered in heart failure, affecting inflammation.", "protein": "Immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC11198551" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation status may be affected in diabetes.", "mechanism": "Diabetes may alter P-glycoprotein expression, affecting drug clearance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198551" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation is essential for P-glycoprotein function and drug binding.", "mechanism": "P-glycoprotein inhibitors affect edoxaban dosing in AF patients due to altered drug transport.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198574" }, { "confidence": "high", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation modulates P-glycoprotein's drug efflux activity.", "mechanism": "Inhibition of P-glycoprotein increases edoxaban plasma levels, raising bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Minor glycosylation may affect hemoglobin stability and clearance.", "mechanism": "Low hemoglobin (anemia) is associated with increased risk of adverse outcomes in anticoagulated AF patients.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation status may influence hemoglobin function.", "mechanism": "Anemia (low hemoglobin) is linked to higher risk of stroke in AF patients.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation may affect hemoglobin degradation.", "mechanism": "Anemia increases risk of bleeding events in anticoagulated AF patients.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11198574" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Altered glycosylation affects transferrin function and iron transport.", "mechanism": "Transferrin glycosylation status can reflect iron metabolism and anemia risk (inferred).", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Systemic Embolism", "glycan_involvement": "Glycosylation modulates P-glycoprotein's substrate specificity.", "mechanism": "Drug interactions via P-glycoprotein may alter anticoagulant efficacy, impacting embolism risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Death", "glycan_involvement": "Glycosylation may influence hemoglobin turnover.", "mechanism": "Lower hemoglobin levels are associated with increased mortality in anticoagulated AF patients.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Death", "glycan_involvement": "Glycosylation is critical for P-glycoprotein's drug transport function.", "mechanism": "P-glycoprotein-mediated drug interactions may affect survival outcomes in AF patients on edoxaban.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198574" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation is essential for P-glycoprotein's proper folding and drug transport function.", "mechanism": "P-glycoprotein mediates drug interactions affecting DOAC dosing in AF patients.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198603" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation modulates P-glycoprotein stability and localization in renal tissues.", "mechanism": "Renal dysfunction alters P-glycoprotein-mediated drug clearance, impacting DOAC safety.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198603" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation status may affect substrate specificity and transport efficiency.", "mechanism": "P-glycoprotein pathway influences DOAC efficacy, affecting stroke risk in AF/CKD patients.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198603" }, { "confidence": "low", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation affects P-glycoprotein's ability to efflux anticoagulants.", "mechanism": "Altered P-glycoprotein function can lead to inappropriate DOAC levels, increasing bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC11198603" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation affects receptor function and drug binding.", "mechanism": "Inhibition reduces platelet aggregation and thrombosis in ACS.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation modulates receptor surface expression.", "mechanism": "Antagonists prevent platelet activation, reducing ACS events.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Heparin binding depends on glycoprotein antithrombin glycosylation.", "mechanism": "Heparins enhance antithrombin activity, preventing clot formation.", "protein": "Heparins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute heart failure (HF)", "glycan_involvement": "N-glycosylation regulates ACE stability and activity.", "mechanism": "ACE inhibitors reduce afterload and improve HF outcomes.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute heart failure (HF)", "glycan_involvement": "Glycosylation influences receptor signaling and drug response.", "mechanism": "Beta-blockers modulate heart rate and contractility in HF.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute heart failure (HF)", "glycan_involvement": "O-glycosylation affects peptide stability and detection.", "mechanism": "BNP levels indicate cardiac stress and HF severity.", "protein": "Natriuretic peptides (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation may affect assay sensitivity.", "mechanism": "Elevated troponin T signals myocardial injury in ACS.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC11198630" }, { "confidence": "medium", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "N-glycosylation modulates fibrin polymerization.", "mechanism": "High fibrinogen levels correlate with thrombosis risk in ACS.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198630" }, { "confidence": "medium", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation regulates multimer formation and activity.", "mechanism": "Elevated levels indicate endothelial dysfunction and risk of ACS.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC11198630" }, { "confidence": "low", "disease": "Acute heart failure (HF)", "glycan_involvement": "N-glycosylation changes are associated with inflammation.", "mechanism": "Altered transferrin glycoforms may reflect HF severity.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11198630" }, { "confidence": "high", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation affects P-glycoprotein drug transport function.", "mechanism": "P-glycoprotein inhibitors increase edoxaban exposure, raising bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "N-glycosylation modulates Factor X secretion and activity.", "mechanism": "Edoxaban inhibits Factor Xa, reducing thromboembolic risk in AF.", "protein": "Coagulation factors (e.g., Factor X)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "high", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation required for protein stability and function.", "mechanism": "VKAs inhibit carboxylation of vitamin K-dependent glycoproteins, impairing coagulation.", "protein": "Vitamin K-dependent proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation status not directly discussed.", "mechanism": "Drop in hemoglobin used to define major bleeding events.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Systemic Thromboembolism", "glycan_involvement": "N-glycosylation regulates platelet receptor function.", "mechanism": "Platelet glycoproteins mediate aggregation, contributing to thromboembolic risk.", "protein": "Platelet glycoproteins (e.g., GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycosylation modulates tPA stability and function.", "mechanism": "tPA used in stroke management; glycosylation affects activity.", "protein": "Tissue Plasminogen Activator (tPA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation impacts protein clearance and immune response.", "mechanism": "Streptokinase used for thrombolysis in MI; glycosylation affects immunogenicity.", "protein": "Streptokinase", "protein_enriched": { "function": "", "gene_name": "Amy2a5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00688" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "high", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycosylation essential for P-glycoprotein trafficking and function.", "mechanism": "P-glycoprotein inhibitors require edoxaban dose adjustment in AF patients.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Major Bleeding", "glycan_involvement": "Glycosylation modulates platelet adhesion and aggregation.", "mechanism": "Platelet glycoprotein function influences bleeding risk during anticoagulation.", "protein": "Platelet glycoproteins (e.g., GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC11198645" }, { "confidence": "medium", "disease": "Valve Thrombosis", "glycan_involvement": "Glycosylation required for protein secretion and activity.", "mechanism": "Impaired carboxylation increases risk of valve thrombosis.", "protein": "Vitamin K-dependent proteins", "relationship_type": "causal", "source_pmcid": "PMC11198645" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "SAA is glycosylated, which affects its solubility and function.", "mechanism": "SAA increases in serum during inflammation as an acute-phase response.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Hp is heavily glycosylated, influencing its stability and immune function.", "mechanism": "Hp levels change in response to inflammation and trauma.", "protein": "Haptoglobin (Hp)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Bone metabolism disorder", "glycan_involvement": "OC is glycosylated, affecting its secretion and activity.", "mechanism": "OC reflects bone turnover and metabolic activity.", "protein": "Osteocalcin (OC)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Bone metabolism disorder", "glycan_involvement": "Glycosylation modulates b-ALP enzymatic activity.", "mechanism": "b-ALP is a marker of bone formation and turnover.", "protein": "Bone Alkaline Phosphatase (b-ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Bone metabolism disorder", "glycan_involvement": "PYD is derived from glycoprotein collagen; glycosylation affects collagen structure.", "mechanism": "PYD reflects collagen cross-linking and bone resorption.", "protein": "Pyridinoline Cross-links (PYD)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Acute bleeding (hemorrhage)", "glycan_involvement": "Glycosylation may affect SAA kinetics in circulation.", "mechanism": "SAA is expected to rise in acute bleeding if inflammation occurs, but did not change in short-term sampling.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Acute bleeding (hemorrhage)", "glycan_involvement": "Glycosylation influences Hp clearance and hemoglobin binding.", "mechanism": "Hp may decrease in acute bleeding due to hemolysis, but did not change in this study.", "protein": "Haptoglobin (Hp)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Hypovolemic shock", "glycan_involvement": "Glycosylation may modulate SAA's inflammatory signaling.", "mechanism": "SAA is a marker for systemic inflammation in shock, but no change observed in short-term bleeding.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Hypovolemic shock", "glycan_involvement": "Glycosylation affects Hp's hemoglobin binding and immune modulation.", "mechanism": "Hp can indicate hemolysis in shock, but levels unchanged in this acute model.", "protein": "Haptoglobin (Hp)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "medium", "disease": "Acute bleeding (hemorrhage)", "glycan_involvement": "Glycosylation regulates b-ALP activity and stability.", "mechanism": "b-ALP is a bone turnover marker; no significant change in acute bleeding.", "protein": "Bone Alkaline Phosphatase (b-ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC11199747" }, { "confidence": "high", "disease": "EDTA-dependent pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "\u03b1IIb\u03b23 is a glycoprotein; glycosylation may affect epitope exposure and antibody binding.", "mechanism": "EDTA induces exposure of neoepitopes on \u03b1IIb\u03b23, leading to antibody-mediated platelet agglutination and clumping.", "protein": "Glycoprotein \u03b1IIb\u03b23 (integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC11199765" }, { "confidence": "medium", "disease": "Glanzmann disease", "glycan_involvement": "Loss of glycoprotein prevents antibody binding; glycosylation status not directly discussed.", "mechanism": "Platelets from Glanzmann patients lack functional \u03b1IIb\u03b23, preventing EDTA-induced pseudothrombocytopenia.", "protein": "Glycoprotein \u03b1IIb\u03b23 (integrin \u03b1IIb\u03b23)", "relationship_type": "protective", "source_pmcid": "PMC11199765" }, { "confidence": "medium", "disease": "EDTA-dependent pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "P-selectin is a glycoprotein; glycosylation may modulate its surface expression and function.", "mechanism": "EDTA-induced activation of \u03b1IIb\u03b23 leads to P-selectin expression, promoting platelet aggregation.", "protein": "P-selectin (GMP-140)", "protein_enriched": { "function": "Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 comple", "gene_name": "BLOC1S1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5R7L8" }, "relationship_type": "causal", "source_pmcid": "PMC11199765" }, { "confidence": "medium", "disease": "EDTA-dependent pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "CD63 is a glycoprotein; glycosylation may affect its trafficking and function.", "mechanism": "EDTA-induced platelet activation increases CD63 expression, contributing to aggregation.", "protein": "Gp55 (CD63)", "relationship_type": "causal", "source_pmcid": "PMC11199765" }, { "confidence": "medium", "disease": "EDTA-dependent pseudothrombocytopenia (EDTA-PTCP)", "glycan_involvement": "Thrombospondin is a glycoprotein; glycosylation may influence its adhesive properties.", "mechanism": "EDTA-induced activation leads to thrombospondin release, facilitating platelet clumping.", "protein": "Thrombospondin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11199765" }, { "confidence": "low", "disease": "True thrombocytopenia", "glycan_involvement": "Glycosylation may affect detection/antibody binding in diagnostic assays.", "mechanism": "Absence of \u03b1IIb\u03b23-mediated aggregation distinguishes true thrombocytopenia from pseudothrombocytopenia.", "protein": "Glycoprotein \u03b1IIb\u03b23 (integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC11199765" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Type IV collagen is a glycoprotein; its glycosylation is essential for ECM structure and fibrosis.", "mechanism": "Serum levels of type IV collagen 7S reflect subclinical liver fibrosis.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC11199833" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Glycosylation of type IV collagen affects ECM remodeling in the atrium.", "mechanism": "Elevated type IV collagen 7S is associated with increased risk of AF via shared fibrotic pathways.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC11199833" }, { "confidence": "medium", "disease": "Left atrial low-voltage areas (LVAs)", "glycan_involvement": "Glycosylation modulates collagen's role in fibrosis and electrical remodeling.", "mechanism": "Higher serum type IV collagen 7S correlates with presence and size of LA LVAs, indicating atrial fibrosis.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC11199833" }, { "confidence": "medium", "disease": "AF recurrence after catheter ablation", "glycan_involvement": "Glycosylation status may influence collagen turnover and fibrosis persistence.", "mechanism": "Elevated type IV collagen 7S (reflecting fibrosis) predicts higher risk of AF recurrence post-ablation.", "protein": "Type IV collagen 7S", "relationship_type": "biomarker", "source_pmcid": "PMC11199833" }, { "confidence": "high", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Glycosylation affects receptor trafficking and function.", "mechanism": "Beta-blockers target beta-adrenergic receptors to reduce AF incidence post-CABG.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "N-glycosylation modulates channel gating and cell surface expression.", "mechanism": "Amiodarone blocks sodium channels, reducing arrhythmogenic activity.", "protein": "Sodium channel (Nav1.5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "N-glycosylation is essential for channel folding and trafficking.", "mechanism": "Amiodarone inhibits hERG channels, prolonging repolarization and preventing AF.", "protein": "Potassium channel (Kv11.1/hERG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Glycosylation regulates channel stability and function.", "mechanism": "Calcium channel blockers reduce AF by modulating Cav1.2 activity.", "protein": "Calcium channel (Cav1.2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Ventricular fibrillation (VF)", "glycan_involvement": "Glycosylation influences receptor responsiveness.", "mechanism": "Beta-blockers decrease VF risk by antagonizing beta-adrenergic signaling.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Ventricular fibrillation (VF)", "glycan_involvement": "N-glycosylation affects channel localization and function.", "mechanism": "Amiodarone blocks sodium channels, lowering VF incidence post-CABG.", "protein": "Sodium channel (Nav1.5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Ventricular fibrillation (VF)", "glycan_involvement": "N-glycosylation required for channel maturation.", "mechanism": "Amiodarone inhibits hERG, reducing VF by prolonging QT interval.", "protein": "Potassium channel (Kv11.1/hERG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "high", "disease": "Postoperative arrhythmia after CABG", "glycan_involvement": "Glycosylation modulates receptor function and drug response.", "mechanism": "Beta-blockers are frequently used to manage postoperative arrhythmias.", "protein": "Beta-adrenergic receptor", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "ADRB2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07550" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Postoperative arrhythmia after CABG", "glycan_involvement": "N-glycosylation impacts channel activity.", "mechanism": "Amiodarone blocks sodium channels, preventing arrhythmias after CABG.", "protein": "Sodium channel (Nav1.5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "medium", "disease": "Postoperative arrhythmia after CABG", "glycan_involvement": "N-glycosylation is critical for channel function.", "mechanism": "Amiodarone inhibits hERG, reducing arrhythmia risk post-CABG.", "protein": "Potassium channel (Kv11.1/hERG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11199843" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Bacterial glycoproteins may interact with host mucosal glycans, influencing colonization and immune modulation.", "mechanism": "F. prausnitzii produces butyrate and anti-inflammatory factors, supporting gut barrier and immune regulation; reduced abundance is associated with UC, especially severe cases.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11200077" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycoproteins may mediate adhesion to mucosal surfaces and immune signaling.", "mechanism": "F. prausnitzii abundance is reduced in CD; its metabolites (e.g., butyrate) inhibit NF-\u03baB activation, reducing inflammation.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11200077" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycoprotein-mediated interactions may affect colonization and detection.", "mechanism": "Lower levels of F. prausnitzii correlate with increased UC severity.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11200077" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycoprotein structure may influence detection and host response.", "mechanism": "Decreased F. prausnitzii distinguishes CD patients from healthy controls.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11200077" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycoprotein-mediated host-microbe interactions may be essential for therapeutic efficacy.", "mechanism": "Restoration of F. prausnitzii (e.g., via probiotics) may ameliorate UC by restoring anti-inflammatory effects.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200077" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycoprotein interactions with host mucosa may be required for colonization and benefit.", "mechanism": "Probiotic supplementation with F. prausnitzii may help maintain remission in CD.", "protein": "Faecalibacterium prausnitzii outer membrane glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200077" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation affects secretion and stability of PAI-1.", "mechanism": "Elevated PAI-1 inhibits fibrinolysis, promotes thrombosis, tissue remodeling, and inflammation, increasing CVD risk.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200361" }, { "confidence": "high", "disease": "Obesity (Severe)", "glycan_involvement": "Glycosylation modulates PAI-1 secretion from adipose tissue.", "mechanism": "PAI-1 expression is upregulated in obesity, linking inflammation and metabolic dysfunction.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200361" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect PAI-1 activity in metabolic tissues.", "mechanism": "Insulin resistance and hyperinsulinemia increase PAI-1 expression, contributing to T2DM pathophysiology.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200361" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation influences PAI-1 function in vascular tissue.", "mechanism": "PAI-1 is elevated in atherosclerotic plaques, promoting plaque stability and thrombosis.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation may regulate hepatic secretion of PAI-1.", "mechanism": "PAI-1 expression is increased in NAFLD, reflecting hepatic inflammation and metabolic risk.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation may modulate PAI-1's interaction with insulin signaling proteins.", "mechanism": "PAI-1 promotes insulin resistance via effects on insulin receptor and inflammatory pathways.", "protein": "PAI-1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "O-glycosylation is essential for adiponectin multimerization and function.", "mechanism": "Adiponectin improves insulin sensitivity; PAI-1 may downregulate adiponectin.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may affect drug responsiveness of PAI-1.", "mechanism": "PAI-1 levels are reduced by hypoglycemic drugs (e.g., metformin), lowering CVD risk.", "protein": "PAI-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may influence PAI-1's effect on lipid metabolism.", "mechanism": "High PAI-1 correlates with low HDL-c, indicating increased CVD risk.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC11200361" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation is required for CRP stability and function.", "mechanism": "High PAI-1 correlates with high CRP, both markers of inflammation and CVD risk.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200361" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Claudin-1 is a glycoprotein; glycosylation is essential for its localization and function in tight junctions.", "mechanism": "Upregulation of Claudin-1 by MexMix improves tight junction integrity, reducing intestinal permeability and inflammation.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC11200377" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Occludin glycosylation is important for tight junction assembly and barrier function.", "mechanism": "MexMix increases Occludin expression, enhancing epithelial barrier and reducing translocation of inflammatory stimuli.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC11200377" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "CD45 is highly glycosylated; glycosylation modulates immune cell signaling.", "mechanism": "Reduced CD45+ cell infiltration in colon after MexMix indicates decreased immune cell-mediated inflammation.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200377" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation affects secretion and receptor interaction.", "mechanism": "MexMix reduces leptin levels, reflecting improved adiposity and metabolic status.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11200377" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Adiponectin glycosylation is critical for multimerization and bioactivity.", "mechanism": "MexMix increases adiponectin, which has anti-inflammatory and insulin-sensitizing effects, improving MASLD.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11200377" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "PAI-1 is glycosylated, which influences stability and activity.", "mechanism": "MexMix reduces PAI-1, associated with improved lipid metabolism and reduced cardiovascular risk.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC11200377" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "GLP-1 is O-glycosylated, affecting stability.", "mechanism": "No significant change in GLP-1 with MexMix; included as a negative finding.", "protein": "GLP-1", "relationship_type": "biomarker", "source_pmcid": "PMC11200377" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "GIP is O-glycosylated, affecting secretion.", "mechanism": "No significant change in GIP with MexMix; included as a negative finding.", "protein": "GIP", "relationship_type": "biomarker", "source_pmcid": "PMC11200377" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Resistin is glycosylated, influencing secretion.", "mechanism": "No significant change in resistin with MexMix; included as a negative finding.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200377" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "TLR4 glycosylation is required for ligand recognition and signaling.", "mechanism": "TLR4 pathway is implicated in MASLD pathogenesis; MexMix did not alter TLR4 expression.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC11200377" }, { "confidence": "high", "disease": "Liver damage", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated ALP indicates hepatocellular injury after CTX exposure.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "high", "disease": "Liver damage", "glycan_involvement": "AST is glycosylated, influencing its plasma half-life.", "mechanism": "Increased AST/GOT in plasma signals liver cell damage from CTX.", "protein": "Aspartate transaminase (AST/GOT)", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "medium", "disease": "Altered lipid metabolism", "glycan_involvement": "Cholesterol is transported by glycosylated lipoproteins.", "mechanism": "Reduced cholesterol levels in CTX-fed fish indicate disrupted lipid metabolism.", "protein": "Cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "medium", "disease": "Altered lipid metabolism", "glycan_involvement": "Triglycerides are carried by glycosylated lipoproteins.", "mechanism": "Lower triglyceride levels reflect impaired hepatic lipid processing after CTX exposure.", "protein": "Triglycerides", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "Many plasma proteins are glycosylated, affecting their function and clearance.", "mechanism": "Altered plasma protein levels may indicate hepatic dysfunction.", "protein": "Total plasma protein", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "low", "disease": "Immune suppression", "glycan_involvement": "Glycosylation maintains RBC membrane integrity.", "mechanism": "Decreased RBC count after CTX exposure may reflect membrane glycoprotein damage.", "protein": "Red blood cell membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11200451" }, { "confidence": "low", "disease": "Immune suppression", "glycan_involvement": "Glycosylation is critical for WBC function and signaling.", "mechanism": "Reduced WBC count suggests immune system impairment due to CTX.", "protein": "White blood cell membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11200451" }, { "confidence": "medium", "disease": "Stress response", "glycan_involvement": "Lactate metabolism is regulated by glycoprotein enzymes.", "mechanism": "Elevated lactate in CTX-fed fish indicates increased metabolic stress.", "protein": "Lactate", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "medium", "disease": "Ciguatera poisoning", "glycan_involvement": "Glycosylation of channel proteins may modulate CTX binding.", "mechanism": "CTX binds to glycoproteins on voltage-gated sodium channels, causing toxicity.", "protein": "Ciguatoxin (CTX)-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11200451" }, { "confidence": "low", "disease": "Growth retardation", "glycan_involvement": "Glucose transport and metabolism involve glycoproteins.", "mechanism": "Altered glucose levels in CTX-fed fish may reflect impaired energy metabolism and growth.", "protein": "Glucose", "relationship_type": "biomarker", "source_pmcid": "PMC11200451" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "C1q is a glycoprotein; glycosylation may affect stability and interaction with A\u03b2.", "mechanism": "A\u03b2 induces C1q, which exacerbates mitochondrial damage via oxidative stress and triggers neuronal death.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11200454" }, { "confidence": "high", "disease": "Age-related macular degeneration", "glycan_involvement": "CFH is N-glycosylated; glycosylation modulates regulatory function.", "mechanism": "CFH inhibits C3 activation, reducing inflammation and oxidative stress in retinal cells.", "protein": "CFH", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11200454" }, { "confidence": "high", "disease": "Myocardial ischemia/infarction", "glycan_involvement": "Glycosylation status affects intracellular vs. extracellular function.", "mechanism": "Intracellular C3 promotes mitochondrial respiration and protects against ischemia/reperfusion injury; deficiency impairs ATP production.", "protein": "C3", "relationship_type": "protective/causal", "source_pmcid": "PMC11200454" }, { "confidence": "high", "disease": "Myocardial ischemia/infarction", "glycan_involvement": "C5 glycosylation required for secretion and function.", "mechanism": "C5a induces ROS and apoptosis via mitochondrial C5aR; inhibition reduces tissue damage.", "protein": "C5", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11200454" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may affect immune complex binding.", "mechanism": "C1q deficiency impairs apoptotic cell clearance, leading to autoimmunity; anti-C1q antibodies are SLE markers.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11200454" }, { "confidence": "medium", "disease": "Viral infections (e.g., measles, adenovirus, CMV, herpes)", "glycan_involvement": "N-glycosylation of CD46 is essential for viral binding.", "mechanism": "CD46 acts as viral entry receptor; viral infection disrupts mitochondrial function.", "protein": "CD46", "protein_enriched": { "function": "Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in th", "gene_name": "CD46", "glycan_count": 60, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G61846BY", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G34989PA", "G40834TG", "G41071NU", "G43223CG", "G45395BF", "G48414YA", "G59324HL", "G60033FS", "G60177UT", "G62765YT", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G94470IW", "G98611JV", "G57321FI", "G03644CB", "G04854VP", "G07810QS", "G08290VR", "G12341GU", "G13131HA", "G15169WU", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G41247ZX", "G43669FQ", "G50856PC", "G57776ZS", "G61256FT", "G69521XL", "G76417NN", "G78649WQ", "G82443XX", "G89827JR", "G90382BL", "G92275SC", "G92551JA", "G94106MV", "G49108TO" ], "uniprot_id": "P15529" }, "relationship_type": "causal/entry receptor", "source_pmcid": "PMC11200454" }, { "confidence": "medium", "disease": "Viral infections (e.g., coxsackievirus B3)", "glycan_involvement": "Glycosylation required for surface expression and viral interaction.", "mechanism": "CD55 serves as co-receptor for viral entry; infection leads to mitochondrial dysfunction.", "protein": "CD55", "protein_enriched": { "function": "Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI)", "gene_name": "DDT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30046" }, "relationship_type": "causal/entry receptor", "source_pmcid": "PMC11200454" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "C1qBP is a glycoprotein; glycosylation may affect C1q binding.", "mechanism": "Release of C1qBP from mitochondria triggers anti-mitochondrial antibodies and dysregulates ATP/ROS.", "protein": "C1qBP", "protein_enriched": { "function": "Multifunctional and multicompartmental protein involved in inflammation and infection processes, ribosome biogenesis, protein synthesis in mitochondria, regulation of apoptosis, transcriptional regula", "gene_name": "C1QBP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G15205QB", "G49108TO" ], "uniprot_id": "Q07021" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200454" }, { "confidence": "medium", "disease": "Myocardial ischemia/infarction", "glycan_involvement": "MBL is heavily glycosylated; glycan recognition is central to function.", "mechanism": "MBL binds DAMPs (e.g., ATP, ROS-induced proteins), activating lectin pathway and inflammation.", "protein": "MBL", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11200454" }, { "confidence": "high", "disease": "Paroxysmal nocturnal hemoglobinuria", "glycan_involvement": "GPI-anchor (glycolipid) is required for membrane localization; loss leads to disease.", "mechanism": "CD59 deficiency leads to unregulated MAC formation and hemolysis.", "protein": "CD59", "protein_enriched": { "function": "Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation (PubMed:11882685, PubMed:1698710, PubMed:2475111, PubMed:24", "gene_name": "CD59", "glycan_count": 226, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G51287LK", "G60554YG", "G74724QE", "G31685JQ", "G12728EY", "G22625SJ", "G47448YK", "G49108TO", "G00176HZ", "G00273SJ", "G00912UN", "G02030ZB", "G02315DX", "G02528FI", "G02815KT", "G03382KH", "G04657PL", "G05962QB", "G06247RL", "G06290IR", "G06330RB", "G06356OH", "G07246CJ", "G07483YN", "G07755XJ", "G08520NM", "G08918WF", "G09831WQ", "G10846ZT", "G11629QQ", "G12341GU", "G12793SR", "G13131HA", "G13191RB", "G13728QT", "G13749ZZ", "G14456RI", "G14882EB", "G14972EH", "G14994KB", "G15169WU", "G15488CF", "G16768LX", "G16828VN", "G17208MA", "G18647XP", "G20312EM", "G22310AV", "G22768VO", "G23133OF", "G23863VK", "G23984SE", "G24835MQ", "G24954UD", "G25418HZ", "G27058EU", "G27126ED", "G27919IH", "G29501UT", "G30740WO", "G30751OD", "G30799SW", "G31596VW", "G31615DN", "G31852PQ", "G32788FZ", "G34617SM", "G34989PA", "G36013ES", "G36134VO", "G36191CD", "G36379GD", "G37412TK", "G37773JL", "G37818NZ", "G39064KU", "G39213VZ", "G39595FH", "G40124HY", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41405QQ", "G42124LM", "G43223CG", "G43669FQ", "G44173IH", "G44215PV", "G44413JJ", "G44778BV", "G45395BF", "G45883VE", "G46487SG", "G46665ZP", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G48414YA", "G50120TH", "G50427EO", "G50856PC", "G51413EV", "G52114WE", "G52358QA", "G52589SM", "G55220VL", "G56087PR", "G56518TU", "G57557NS", "G57776ZS", "G57888GL", "G57939IT", "G58596DI", "G58598BO", "G58667NI", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G61207RZ", "G61256FT", "G61505ZR", "G61806WR", "G62765YT", "G63628AV", "G63640QH", "G63889NK", "G64227LK", "G64394MX", "G64527OM", "G65019XG", "G65092SV", "G66621EA", "G66760KM", "G67164EE", "G67900CJ", "G68833MP", "G69521XL", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71146HJ", "G71463BG", "G71919QK", "G72667IM", "G72797UR", "G72886NH", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77023TY", "G77149EE", "G77669RF", "G78059CC", "G78502KD", "G78649WQ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80858MF", "G80920RR", "G80966KZ", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82348BZ", "G82443XX", "G82830MN", "G83229XP", "G83633GK", "G83646BJ", "G84452RH", "G85269DF", "G85282JO", "G85737WG", "G86182NS", "G86226EA", "G86234IN", "G86357DX", "G86408JD", "G86795LJ", "G86880BF", "G87123QX", "G87618BG", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G90717TP", "G91473PK", "G91636VS", "G92062TF", "G92081HT", "G92135MA", "G92275SC", "G93141AZ", "G93993PD", "G94470IW", "G94831VI", "G95177YH", "G95865ZB", "G95977AE", "G98611JV", "G57321FI", "G01079KY", "G16389EC", "G31544HA", "G46687AB", "G50045TK", "G51519NL", "G71269BI", "G75727PF", "G80218BM", "G83461WR", "G90093AU" ], "uniprot_id": "P13987" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11200454" }, { "confidence": "medium", "disease": "Long-COVID syndrome", "glycan_involvement": "Spike glycoprotein's glycosylation may affect immunogenicity and molecular mimicry.", "mechanism": "Molecular mimicry between spike glycoprotein and host proteins may trigger autoantibody production, contributing to long-COVID symptoms.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11200469" }, { "confidence": "medium", "disease": "Long-COVID syndrome", "glycan_involvement": "Glycosylation may influence receptor's antigenicity and autoantibody recognition.", "mechanism": "Autoantibodies against CRF receptor 2 detected in long-COVID patients, suggesting possible involvement in neurovegetative symptoms.", "protein": "Corticotropin-releasing factor receptor 2", "protein_enriched": { "function": "G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via ", "gene_name": "CRHR2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q13324" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200469" }, { "confidence": "medium", "disease": "Long-COVID syndrome", "glycan_involvement": "Glycosylation may modulate receptor's immune recognition.", "mechanism": "Autoantibodies against CGRP receptor detected in long-COVID patients, possibly contributing to autonomic dysfunction.", "protein": "Calcitonin gene-related peptide type 1 receptor", "protein_enriched": { "function": "G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs) (PubMed:32296767, PubMed:33602864, PubMed:8626685). Together with RAMP1,", "gene_name": "CALCRL", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01650EU", "G02815KT", "G18647XP", "G27058EU", "G28541PG", "G31852PQ", "G37399XV", "G39446WN", "G41247ZX", "G59626AS", "G62765YT", "G63041LO", "G80920RR", "G83460ZZ", "G00912UN", "G08918WF", "G40574BA", "G45526EA" ], "uniprot_id": "Q16602" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200469" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "Glycosylation status may affect susceptibility to autoantibody binding.", "mechanism": "Molecular mimicry with SARS-CoV-2 spike glycoprotein may induce autoimmunity against CRF receptor 2.", "protein": "Corticotropin-releasing factor receptor 2", "protein_enriched": { "function": "G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via ", "gene_name": "CRHR2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q13324" }, "relationship_type": "causal", "source_pmcid": "PMC11200469" }, { "confidence": "low", "disease": "Autoimmune disease (general)", "glycan_involvement": "Glycosylation may influence antigenic properties.", "mechanism": "Molecular mimicry with spike glycoprotein may trigger autoimmunity against CGRP receptor.", "protein": "Calcitonin gene-related peptide type 1 receptor", "protein_enriched": { "function": "G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs) (PubMed:32296767, PubMed:33602864, PubMed:8626685). Together with RAMP1,", "gene_name": "CALCRL", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01650EU", "G02815KT", "G18647XP", "G27058EU", "G28541PG", "G31852PQ", "G37399XV", "G39446WN", "G41247ZX", "G59626AS", "G62765YT", "G63041LO", "G80920RR", "G83460ZZ", "G00912UN", "G08918WF", "G40574BA", "G45526EA" ], "uniprot_id": "Q16602" }, "relationship_type": "causal", "source_pmcid": "PMC11200469" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "Glycosylation patterns affect immune response and mimicry potential.", "mechanism": "Exposure to spike glycoprotein (infection or vaccination) may induce autoantibodies via molecular mimicry.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11200469" }, { "confidence": "low", "disease": "Postural orthostatic tachycardia syndrome (POTS)", "glycan_involvement": "Glycosylation may affect receptor's immune visibility.", "mechanism": "Autoantibodies may contribute to autonomic dysfunction seen in POTS-like symptoms in long-COVID.", "protein": "Corticotropin-releasing factor receptor 2", "protein_enriched": { "function": "G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via ", "gene_name": "CRHR2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q13324" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200469" }, { "confidence": "low", "disease": "Postural orthostatic tachycardia syndrome (POTS)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies may play a role in autonomic symptoms post-COVID.", "protein": "Calcitonin gene-related peptide type 1 receptor", "protein_enriched": { "function": "G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs) (PubMed:32296767, PubMed:33602864, PubMed:8626685). Together with RAMP1,", "gene_name": "CALCRL", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01650EU", "G02815KT", "G18647XP", "G27058EU", "G28541PG", "G31852PQ", "G37399XV", "G39446WN", "G41247ZX", "G59626AS", "G62765YT", "G63041LO", "G80920RR", "G83460ZZ", "G00912UN", "G08918WF", "G40574BA", "G45526EA" ], "uniprot_id": "Q16602" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200469" }, { "confidence": "medium", "disease": "Long-COVID syndrome", "glycan_involvement": "Glycosylation affects antibody binding and immune response.", "mechanism": "Detection of anti-spike antibodies may indicate exposure and risk for long-COVID.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11200469" }, { "confidence": "low", "disease": "Long-COVID syndrome", "glycan_involvement": "Glycosylation may influence therapeutic antibody design.", "mechanism": "Potential target for intervention if autoimmunity is confirmed.", "protein": "Corticotropin-releasing factor receptor 2", "protein_enriched": { "function": "G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via ", "gene_name": "CRHR2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q13324" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200469" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation affects stability and function as an acute-phase reactant.", "mechanism": "Serum Amyloid A levels correlate positively with hemogram-derived inflammatory markers, reflecting systemic inflammation in CKD.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation modulates immunomodulatory properties.", "mechanism": "Alpha-1-acid glycoprotein is an acute-phase protein elevated in chronic inflammation, including CKD.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation influences albumin's half-life and function.", "mechanism": "Serum albumin concentration negatively correlates with NLR and MLR, indicating inflammation and disease progression.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation affects immunoglobulin function.", "mechanism": "Globulin levels positively correlate with NLR and MLR, reflecting inflammatory status in CKD.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation required for CRP secretion and activity.", "mechanism": "PLR correlates with high-sensitivity C-reactive protein in human CKD, indicating inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates acute-phase response.", "mechanism": "Elevated in neoplastic conditions, correlates with inflammatory markers.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects immunomodulation.", "mechanism": "Elevated in cancer, reflects systemic inflammation.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "low", "disease": "High-grade Lymphoma", "glycan_involvement": "Glycosylation impacts stability.", "mechanism": "Low albumin associated with inflammation and poor prognosis in lymphoma.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "low", "disease": "Acute Pancreatitis", "glycan_involvement": "Glycosylation modulates anti-inflammatory activity.", "mechanism": "Elevated in acute inflammation, including pancreatitis.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "low", "disease": "Hypertrophic Cardiomyopathy", "glycan_involvement": "Glycosylation affects function.", "mechanism": "Elevated in cardiac inflammation, correlates with hemogram-derived markers.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC11200498" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation affects AAT stability and function; deficiency often involves glycosylation defects.", "mechanism": "AAT deficiency disrupts protease-antiprotease balance, leading to lung tissue destruction and increased COPD risk.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "CRP is glycosylated; glycosylation modulates its stability and inflammatory signaling.", "mechanism": "CRP levels are elevated in COPD, reflecting systemic and airway inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation influences PCT secretion and stability.", "mechanism": "PCT increases during inflammation and infection, correlating with COPD severity and exacerbations.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "NE is elevated in COPD, drives airway inflammation and tissue destruction.", "protein": "Neutrophil elastase", "protein_enriched": { "function": "Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of", "gene_name": "ELANE", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G93279DZ", "G00395TQ", "G08290VR", "G11870QZ", "G27058EU", "G28681TP", "G29299MO", "G47644PP", "G47950XN", "G61334IA", "G82348BZ", "G00912UN", "G11314AS", "G25637MV", "G36379GD", "G59626AS", "G72291OX", "G95865ZB" ], "uniprot_id": "P08246" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200520" }, { "confidence": "high", "disease": "Emphysema", "glycan_involvement": "N-glycosylation required for AAT inhibitory function.", "mechanism": "AAT inhibits NE; deficiency leads to unchecked NE activity and emphysema.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11200520" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in COVID-19 infection, reflecting acute inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycan involvement.", "mechanism": "NE is elevated in COVID-19, associated with airway inflammation.", "protein": "Neutrophil elastase", "protein_enriched": { "function": "Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of", "gene_name": "ELANE", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G93279DZ", "G00395TQ", "G08290VR", "G11870QZ", "G27058EU", "G28681TP", "G29299MO", "G47644PP", "G47950XN", "G61334IA", "G82348BZ", "G00912UN", "G11314AS", "G25637MV", "G36379GD", "G59626AS", "G72291OX", "G95865ZB" ], "uniprot_id": "P08246" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "N-glycosylation affects AAT function.", "mechanism": "AAT may protect against airway inflammation in asthma.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11200520" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates CRP activity.", "mechanism": "CRP may be elevated in asthma, indicating inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences PCT stability.", "mechanism": "PCT increases in severe COVID-19, reflecting bacterial co-infection and inflammation.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11200520" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "OLFM4 is a glycoprotein; glycosylation may affect stability or secretion, but not directly discussed.", "mechanism": "OLFM4 interacts with p62 to promote hepatic mitophagy; OLFM4 knockout exacerbates MASLD by decreasing mitophagy.", "protein": "Olfactomedin 4 (OLFM4)", "protein_enriched": { "function": "May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apop", "gene_name": "OLFM4", "glycan_count": 56, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G27947YN", "G32788FZ", "G37818NZ", "G45395BF", "G45495MK", "G57776ZS", "G79666IR", "G84452RH", "G93718GY", "G05962QB", "G07810QS", "G23719VF", "G34989PA", "G39471UU", "G47644PP", "G63041LO", "G67164EE", "G70232NH", "G90659AW", "G11629QQ", "G15169WU", "G51413EV", "G02815KT", "G05724UK", "G06110VR", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G59626AS", "G59924QI", "G92050GC", "G92406TI", "G95865ZB", "G04657PL", "G08290VR", "G08918WF", "G10486CT", "G11314AS", "G18647XP", "G22310AV", "G27126ED", "G29299MO", "G36013ES", "G46691LC", "G47950XN", "G70441OD", "G70619PT", "G81198YO", "G85269DF", "G35541EV", "G55132BD", "G75983OB", "G80075MS", "G95046LV" ], "uniprot_id": "Q6UX06" }, "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "p62 mediates Parkin-independent mitophagy; impaired p62 function leads to mitophagy arrest and MASLD progression.", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "causal", "source_pmcid": "PMC11200567" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "BNIP3-mediated mitophagy reduces ROS, inflammation, and steatohepatitis; loss of BNIP3 increases disease severity.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Parkin-dependent mitophagy prevents mitochondrial dysfunction and hepatocyte apoptosis; loss of Parkin exacerbates MASLD.", "protein": "Parkin (PARK2)", "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "PINK1 recruits Parkin to damaged mitochondria, promoting mitophagy and protecting against MASLD.", "protein": "PINK1", "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "SIRT3 activates BNIP3-mediated mitophagy, blocking mitochondrial apoptosis and reducing steatosis.", "protein": "SIRT3", "protein_enriched": { "function": "NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:19535340, PubMed:23283301, PubMed:24121500, PubMed:24252090). Activates o", "gene_name": "SIRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NTG7" }, "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "RNF31 promotes p53 degradation, increasing BNIP3 expression and mitophagy, reducing lipid deposition and apoptosis.", "protein": "RNF31", "protein_enriched": { "function": "E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of i", "gene_name": "RNF31", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96EP0" }, "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "PRDX6 enhances mitophagy by suppressing Notch signaling, reducing hepatic lipid accumulation.", "protein": "PRDX6", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (PubMed:10893423, PubMed:9497358). Can reduce H(2)O(2) and sh", "gene_name": "PRDX6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30041" }, "relationship_type": "protective", "source_pmcid": "PMC11200567" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TIM-4 is a glycoprotein; glycosylation may affect ligand binding, but not directly discussed.", "mechanism": "TIM-4 activation in Kupffer cells promotes fibrosis via PINK1/Parkin-mediated mitophagy and TGF-\u03b21 expression.", "protein": "TIM-4", "protein_enriched": { "function": "Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation. Controls T-cell activation in a bimodal fashion, decreasing th", "gene_name": "TIMD4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q96H15" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200567" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "PTPROt is a membrane protein; glycosylation may affect function, but not directly discussed.", "mechanism": "PTPROt in macrophages activates NF-\u03baB and NLRP3/IL1\u03b2 axis (pro-inflammatory), but also activates mitophagy to restrict inflammation.", "protein": "PTPROt", "protein_enriched": { "function": "Possesses tyrosine phosphatase activity. Plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function (By similarity)", "gene_name": "PTPRO", "glycan_count": 6, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G28541PG", "G31852PQ", "G41247ZX", "G62765YT", "G49108TO", "G02815KT" ], "uniprot_id": "Q16827" }, "relationship_type": "dual (causal/protective)", "source_pmcid": "PMC11200567" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "Lf is a glycoprotein; glycosylation may affect receptor binding and nanoparticle targeting.", "mechanism": "Lf-targeted nanoparticles deliver betulinic acid to TNBC cells via transferrin receptor-mediated uptake, enhancing cytotoxicity.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "ASGPR recognizes galactose residues on glycoproteins; glycosylation is essential for targeting.", "mechanism": "Galactosylated chitosan nanoparticles target hepatocytes via ASGPR, delivering betulinic acid to reduce fibrosis.", "protein": "Asialoglycoprotein receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "FAR is a glycoprotein; glycosylation may influence ligand binding and cell targeting.", "mechanism": "Folate-conjugated micelles/liposomes deliver betulin derivatives to FAR-overexpressing breast cancer cells.", "protein": "Folate receptor (FAR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Transferrin receptor is a glycoprotein; glycosylation modulates receptor function.", "mechanism": "Lf-targeted nanoparticles exploit transferrin receptor overexpression for enhanced drug delivery to cancer cells.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Non-small-cell lung carcinoma", "glycan_involvement": "Albumin has minor N-glycosylation; may affect nanoparticle stability and targeting.", "mechanism": "Albumin-based nanoparticles deliver betulinic acid and doxorubicin to NSCLC cells, increasing cytotoxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Enzyme produces cyclodextrins (glycans) used as drug carriers.", "mechanism": "Cyclodextrin complexes increase solubility and delivery of betulinic acid to melanoma cells.", "protein": "Cyclodextrin glycosyltransferase", "protein_enriched": { "function": "", "gene_name": "amyS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06278" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "Glycolipid biosurfactant improves liposome-cell membrane fusion.", "mechanism": "Glycolipid-coated liposomes enhance delivery of betulinic acid to HepG2 cells.", "protein": "Mannosylerythritol lipid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "FAR glycosylation may affect folate binding and targeting.", "mechanism": "Folate-modified liposomes selectively deliver betulinic acid to FR-positive HepG2 cells.", "protein": "Folate receptor (FAR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Lf glycosylation may influence receptor interaction.", "mechanism": "Lf-modified nanoparticles target breast cancer cells via receptor-mediated endocytosis.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "ASGPR recognizes galactose on glycoproteins; glycosylation is critical.", "mechanism": "Galactosylated nanoparticles target ASGPR on hepatocytes for betulinic acid delivery.", "protein": "Asialoglycoprotein receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200571" }, { "confidence": "high", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Hepcidin is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Hepcidin is overproduced in VTE, reflecting inflammation and iron dysregulation.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "gp130 is a glycoprotein; glycosylation is essential for receptor function.", "mechanism": "IL-6/gp130 signaling induces hepcidin expression via JAK2/STAT pathway during inflammation in VTE.", "protein": "gp130 (IL6ST)", "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Transferrin is N-glycosylated; glycosylation affects iron binding and half-life.", "mechanism": "Transferrin-bound iron is measured to assess iron status in VTE patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Ceruloplasmin is heavily glycosylated; glycosylation is critical for secretion and activity.", "mechanism": "Ceruloplasmin forms complexes with ferroportin, modulating iron export and oxidative stress in VTE.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Ferroportin is glycosylated; glycosylation may affect cell surface expression.", "mechanism": "Hepcidin binds ferroportin, causing its internalization and degradation, reducing plasma iron and contributing to VTE-associated iron dysregulation.", "protein": "Ferroportin", "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "Plasminogen is glycosylated; glycosylation modulates activation and function.", "mechanism": "Oxidative stress inhibits plasminogen activation, reducing fibrinolysis and promoting thrombosis.", "protein": "Plasminogen", "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation may affect hepcidin's bioavailability.", "mechanism": "Elevated hepcidin reflects inflammation and iron dysregulation in DVT.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Pulmonary Embolism (PE)", "glycan_involvement": "Glycosylation may affect hepcidin's stability.", "mechanism": "Increased hepcidin observed in PE, indicating inflammatory and iron regulatory involvement.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200582" }, { "confidence": "low", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation required for gp130 function.", "mechanism": "IL-6/gp130 pathway activation increases hepcidin, contributing to iron dysregulation in DVT.", "protein": "gp130 (IL6ST)", "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "low", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation essential for ceruloplasmin function.", "mechanism": "Ceruloplasmin-ferroportin interaction modulates iron export and oxidative stress in DVT.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "causal", "source_pmcid": "PMC11200582" }, { "confidence": "medium", "disease": "Premature ovarian failure", "glycan_involvement": "EMILIN1 is a glycoprotein; glycosylation may affect its ECM localization and function.", "mechanism": "EMILIN1 depletion increases follicle activation and depletion, reducing ovarian reserve longevity.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "medium", "disease": "Infertility", "glycan_involvement": "Glycosylation may modulate EMILIN1's interaction with ECM and growth factors.", "mechanism": "Loss of EMILIN1 in ovarian ECM impairs follicle growth and survival, leading to reduced fertility.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "high", "disease": "Folliculogenesis defects", "glycan_involvement": "Glycosylation may regulate EMILIN1's binding to TGF\u03b2 precursors.", "mechanism": "EMILIN1 antagonizes TGF\u03b2 signaling; its depletion activates TGF\u03b2 pathways, altering granulosa cell proliferation and follicle activation.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "medium", "disease": "Endocrine dysfunction", "glycan_involvement": "Glycosylation status may affect EMILIN1's ECM stability and signaling.", "mechanism": "Depletion of EMILIN1 from ovarian ECM reduces follicle survival and growth, impairing endocrine function.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "ZP3 is heavily glycosylated; glycans are critical for sperm binding and fertilization.", "mechanism": "ZP3 is essential for oocyte structure and fertilization; its depletion disrupts oocyte-granulosa cell interactions.", "protein": "ZP3", "protein_enriched": { "function": "Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellu", "gene_name": "ZP3", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G62765YT", "G00031MO", "G00033MO", "G00468NI", "G01614ZM", "G02368JK", "G03670RH", "G07575HR", "G11457RF", "G13260JU", "G14669DU", "G25323VU", "G29931IJ", "G32550BI", "G33508VK", "G34985XL", "G42797SX", "G46748BU", "G48856VC", "G51827GO", "G52144RR", "G59229NY", "G60145BJ", "G60554YG", "G63628AV", "G64973KT", "G67561OD", "G81006GJ", "G85079IJ", "G90507NI" ], "uniprot_id": "P21754" }, "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "medium", "disease": "Folliculogenesis defects", "glycan_involvement": "Glycosylation of ZP3 modulates its structural and functional properties.", "mechanism": "Altered ZP3 abundance affects follicle activation and oocyte maturation.", "protein": "ZP3", "protein_enriched": { "function": "Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellu", "gene_name": "ZP3", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G62765YT", "G00031MO", "G00033MO", "G00468NI", "G01614ZM", "G02368JK", "G03670RH", "G07575HR", "G11457RF", "G13260JU", "G14669DU", "G25323VU", "G29931IJ", "G32550BI", "G33508VK", "G34985XL", "G42797SX", "G46748BU", "G48856VC", "G51827GO", "G52144RR", "G59229NY", "G60145BJ", "G60554YG", "G63628AV", "G64973KT", "G67561OD", "G81006GJ", "G85079IJ", "G90507NI" ], "uniprot_id": "P21754" }, "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "medium", "disease": "Folliculogenesis defects", "glycan_involvement": "COL4 is glycosylated; glycans contribute to ECM assembly and cell adhesion.", "mechanism": "COL4 maintains ECM structure; its preservation supports follicle survival and growth.", "protein": "COL4 (Collagen IV)", "relationship_type": "protective", "source_pmcid": "PMC11200611" }, { "confidence": "high", "disease": "TGF\u03b2 signaling dysregulation", "glycan_involvement": "Glycosylation may influence EMILIN1's interaction with TGF\u03b2 precursors.", "mechanism": "EMILIN1 deficiency leads to increased TGF\u03b2 bioavailability and signaling, impacting follicle development.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "low", "disease": "Cancer metastasis to ovary", "glycan_involvement": "Glycosylation may affect EMILIN1's ECM retention and detection.", "mechanism": "EMILIN1 localization in ovarian ECM may be altered in metastatic disease, affecting tissue eligibility for transplantation.", "protein": "EMILIN1", "relationship_type": "biomarker", "source_pmcid": "PMC11200611" }, { "confidence": "low", "disease": "Osteoporosis/Cardiovascular disease/Declining cognitive function", "glycan_involvement": "Indirect; EMILIN1 glycosylation affects ovarian ECM and endocrine longevity.", "mechanism": "Loss of ovarian endocrine function (linked to EMILIN1 depletion and follicle loss) increases risk of these comorbidities.", "protein": "EMILIN1", "relationship_type": "causal", "source_pmcid": "PMC11200611" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "gp130 is a glycoprotein receptor; glycosylation affects receptor function and signaling.", "mechanism": "gp130 mediates IL-6/STAT3 signaling affecting aqueous humor outflow and IOP regulation.", "protein": "Glycoprotein 130 (gp130)", "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "IL6R glycosylation regulates receptor stability and ligand binding.", "mechanism": "Elevated soluble IL6R in aqueous humor of POAG patients; modulates IL-6 trans-signaling.", "protein": "Interleukin-6 receptor (IL6R)", "relationship_type": "biomarker", "source_pmcid": "PMC11200618" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "STAT3 interacts with glycoprotein receptors; glycosylation of upstream proteins affects pathway.", "mechanism": "STAT3 activation downstream of IL-6/gp130 modulates glycolysis and mitochondrial function in HTM cells.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "medium", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "CSTA is a glycoprotein; glycosylation may affect inhibitor activity.", "mechanism": "CSTA reduces cleavage of MYOC in TM cells, potentially protecting against MYOC-induced glaucoma.", "protein": "Cystatin A (CSTA)", "protein_enriched": { "function": "This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis", "gene_name": "CSTA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P01040" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200618" }, { "confidence": "medium", "disease": "Ocular Hypertension", "glycan_involvement": "S1PR3 is a glycoprotein; glycosylation may modulate receptor signaling.", "mechanism": "S1PR3 activation increases aqueous humor outflow resistance, elevating IOP.", "protein": "Sphingosine-1-phosphate receptor 3 (S1PR3)", "protein_enriched": { "function": "Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat", "gene_name": "S1PR3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99500" }, "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "MYOC is glycosylated; glycosylation affects secretion and aggregation.", "mechanism": "Mutations and altered cleavage of MYOC in TM cells contribute to glaucoma pathogenesis.", "protein": "Myocilin (MYOC)", "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "medium", "disease": "Steroid-induced Glaucoma", "glycan_involvement": "TGF-\u03b22 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "TGF-\u03b22 induces ECM changes and increased outflow resistance in HTM cells.", "protein": "Transforming growth factor beta 2 (TGF-\u03b22)", "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "medium", "disease": "Corneal Dysfunction", "glycan_involvement": "Fibronectin is heavily glycosylated; glycosylation modulates ECM interactions.", "mechanism": "Fibronectin accumulation alters ECM and cell adhesion in ocular tissues.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "high", "disease": "Primary Open Angle Glaucoma (POAG)", "glycan_involvement": "ROCK2 interacts with glycoprotein signaling pathways.", "mechanism": "ROCK2 inhibition by KD025 shifts ATP production from glycolysis to mitochondrial respiration, improving TM cell function.", "protein": "ROCK2", "protein_enriched": { "function": "Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis (By simil", "gene_name": "CXCL16", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G08918WF", "G43223CG", "G62765YT" ], "uniprot_id": "Q9H2A7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200618" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation of receptors modulates JAK/STAT pathway activation.", "mechanism": "JAK/STAT signaling downstream of glycoprotein receptors (IL6R/gp130) promotes cell proliferation and survival.", "protein": "Janus kinase (JAK)", "relationship_type": "causal", "source_pmcid": "PMC11200618" }, { "confidence": "high", "disease": "Oxidative stress-related diseases", "glycan_involvement": "Glycosylation (rutinoside) affects solubility and bioactivity", "mechanism": "Antioxidant activity reduces ROS and oxidative damage", "protein": "Hesperidin (hesperetin 7-rutinoside)", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "Skin inflammation", "glycan_involvement": "Aglycone form (no glycosylation) increases cell permeability and activity", "mechanism": "Reduces NO, TNF-\u03b1, and IL-6 production in keratinocytes", "protein": "Hesperetin", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "Microbial skin infections (S. aureus, C. acnes, C. albicans, M. furfur)", "glycan_involvement": "Esterification (no glycosylation) increases membrane interaction", "mechanism": "High hydrophobicity enhances antimicrobial activity against skin pathogens", "protein": "Hesperetin laurate", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "medium", "disease": "Oxidative stress-related diseases", "glycan_involvement": "Additional glycosylation increases water solubility, may reduce cell entry", "mechanism": "Antioxidant activity, but less potent than aglycone/ester forms", "protein": "Hesperidin glucoside", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "Skin inflammation", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects stability and secretion", "mechanism": "Pro-inflammatory cytokine reduced by hesperetin and derivatives", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "Skin inflammation", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects stability and secretion", "mechanism": "Pro-inflammatory cytokine reduced by hesperetin and derivatives", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "UV-induced skin damage", "glycan_involvement": "No glycosylation; fatty acid ester increases lipophilicity and efficacy", "mechanism": "Reduces inflammatory mediators and cytokines after UV exposure", "protein": "Hesperetin laurate", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation affects absorption and bioactivity", "mechanism": "Antioxidant and anti-inflammatory properties may reduce risk", "protein": "Hesperidin (hesperetin 7-rutinoside)", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Aglycone form increases cell entry and cytotoxicity", "mechanism": "Antioxidant and cytotoxic effects may inhibit cancer cell growth", "protein": "Hesperetin", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "medium", "disease": "Microbial skin infections", "glycan_involvement": "Glycosylation increases hydrophilicity, reduces antimicrobial potency", "mechanism": "Low antimicrobial activity; high water solubility may limit membrane interaction", "protein": "Hesperidin glucoside", "relationship_type": "protective", "source_pmcid": "PMC11200626" }, { "confidence": "high", "disease": "Liver injury in T2DM", "glycan_involvement": "N-glycosylation critical for stability and function of sCD14 as a pattern recognition receptor.", "mechanism": "Elevated sCD14 reflects increased gut permeability and microbial translocation, correlating with liver injury markers.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "high", "disease": "Liver injury in T2DM", "glycan_involvement": "N-glycosylation modulates sCD163 shedding and function.", "mechanism": "sCD163 is a marker of Kupffer cell activation and hepatic inflammation, correlating with hepatocyte death markers.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation required for ligand binding and immune signaling.", "mechanism": "sCD14-mediated monocyte activation links microbial translocation to MASLD development.", "protein": "sCD14", "relationship_type": "causal", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects receptor function and clearance.", "mechanism": "sCD163 elevation indicates Kupffer cell activation in MASLD.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "high", "disease": "Liver injury in T2DM", "glycan_involvement": "O-glycosylation may affect K18 stability and release.", "mechanism": "Elevated K18 fragments indicate hepatocyte apoptosis/necrosis in T2DM-related liver injury.", "protein": "K18 (M30/M65)", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation required for sCD14 secretion.", "mechanism": "sCD14 elevation reflects monocyte/macrophage activation in systemic inflammation.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "N-glycosylation influences sCD163 plasma levels.", "mechanism": "sCD163 correlates with liver fibrosis severity.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "O-glycosylation may modulate fragment release.", "mechanism": "K18 fragments are markers of hepatocyte death in MASLD.", "protein": "K18 (M30/M65)", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation supports receptor function.", "mechanism": "sCD14 is associated with metabolic endotoxemia and insulin resistance.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation affects sCD163 stability.", "mechanism": "sCD163 is elevated in advanced liver disease including cirrhosis.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC11200675" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Altered glycosylation in tumors affects CD133 stability, function, and immunodetection.", "mechanism": "CD133 marks cancer stem cells responsible for tumor growth, relapse, and metastasis.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "High-mannose N-glycans required for CD133\u2013DNMT1 interaction; complex N-glycans promote DNMT1 nuclear translocation and sensitize cells to therapy.", "mechanism": "High-mannose N-glycosylation of CD133 maintains glioma stem cells in a slow-cycling, chemoresistant state via DNMT1 interaction.", "protein": "CD133 (prominin-1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation at Asn548 is critical for CD133\u2013\u03b2-catenin interaction and cell viability.", "mechanism": "CD133 promotes cell proliferation and anti-apoptosis via \u03b2-catenin and PI3K/Akt pathways.", "protein": "CD133 (prominin-1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Intrahepatic cholangiocarcinoma", "glycan_involvement": "High-mannose (\u03b11,2-mannosylation) enhances autophagy and stemness gene expression.", "mechanism": "\u03b11,2-mannosylated CD133 marks tumor-initiating cells with high self-renewal and tumorigenicity.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11200695" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Sialylated N-glycans stabilize CD133 in exosomes, potentially influencing metastasis.", "mechanism": "CD133 detected in exosomes from patient ascites; sialylation is the major glycosylation type.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11200695" }, { "confidence": "medium", "disease": "Autosomal dominant polycystic kidney disease", "glycan_involvement": "Glycosylation status does not affect detection by targeted proteomics.", "mechanism": "High expression of CD133 in exosomes from patient biofluids detected by mass spectrometry.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation patterns affect antigen recognition and therapy specificity.", "mechanism": "CD133-targeted CAR-T cells can eliminate cancer stem cells.", "protein": "CD133 (prominin-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Complex N-glycosylation required for AC133 epitope detection; altered glycosylation changes antibody binding.", "mechanism": "CD133 glycosylation status influences immunodetection accuracy and prognostic value.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Sialylation and N-glycosylation protect CD133 from degradation and promote malignant phenotype.", "mechanism": "CD133 glycosylation stabilizes the protein, prevents lysosomal degradation, and activates autophagy.", "protein": "CD133 (prominin-1)", "relationship_type": "causal", "source_pmcid": "PMC11200695" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Specific glycan structures correlate with cancer stem cell features.", "mechanism": "CD133 glycosylation patterns are associated with stemness and epithelial\u2013mesenchymal transition.", "protein": "CD133 (prominin-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11200695" }, { "confidence": "high", "disease": "Anemia of CKD", "glycan_involvement": "N-glycosylation required for EPO stability and activity.", "mechanism": "Deficiency of EPO due to impaired renal production leads to reduced erythropoiesis.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "causal", "source_pmcid": "PMC11200696" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "N-glycosylation affects transferrin structure and iron binding.", "mechanism": "Transferrin saturation (TSAT) is used to assess iron status in CKD and anemia.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "Glycosylation influences ferritin secretion and stability.", "mechanism": "Serum ferritin reflects iron stores; altered in CKD due to inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "medium", "disease": "Anemia of CKD", "glycan_involvement": "Glycosylation required for receptor function and shedding.", "mechanism": "sTfR levels correlate with erythropoietic activity and iron deficiency.", "protein": "Soluble Transferrin Receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "high", "disease": "Anemia of CKD", "glycan_involvement": "Glycosylation affects peptide stability and bioactivity.", "mechanism": "Elevated hepcidin inhibits iron absorption and release, worsening anemia.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal", "source_pmcid": "PMC11200696" }, { "confidence": "medium", "disease": "Iron Deficiency", "glycan_involvement": "Glycosylation modulates NGAL secretion and iron-binding properties.", "mechanism": "NGAL correlates with iron status and is sensitive for iron deficiency in CKD.", "protein": "Neutrophil-Gelatinase-Associated Lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "medium", "disease": "Anemia of CKD", "glycan_involvement": "Glycosylation required for BMP-6 signaling.", "mechanism": "BMP-6 regulates hepcidin; anti-BMP-6 antibodies improve anemia and iron metabolism.", "protein": "Bone Morphogenetic Protein 6 (BMP-6)", "protein_enriched": { "function": "Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction", "gene_name": "MYH2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UKX2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200696" }, { "confidence": "medium", "disease": "Anemia of CKD", "glycan_involvement": "O-glycosylation modulates FGF-23 stability and activity.", "mechanism": "Elevated FGF-23 suppresses erythropoiesis and correlates with anemia risk.", "protein": "Fibroblast Growth Factor 23 (FGF-23)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "low", "disease": "Cancer progression", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "EPOR expression on neoplastic cells may mediate ESA-induced cancer progression.", "protein": "EPO Receptor (EPOR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200696" }, { "confidence": "high", "disease": "Inflammation-associated anemia", "glycan_involvement": "Glycosylation required for CRP secretion and function.", "mechanism": "CRP is used to distinguish inflammation-driven changes in iron biomarkers.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11200696" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; TRF2 is a nuclear glycoprotein.", "mechanism": "TRF2 maintains telomere integrity, preventing cellular senescence and apoptosis.", "protein": "TRF2", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "medium", "disease": "Behcet\u2019s disease", "glycan_involvement": "Not specified in article.", "mechanism": "TRF2 deficiency promotes cellular senescence and apoptosis in Behcet\u2019s disease.", "protein": "TRF2", "relationship_type": "causal", "source_pmcid": "PMC11200722" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not specified in article.", "mechanism": "RAP1 protects against obesity by maintaining telomere function.", "protein": "RAP1", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Not specified in article.", "mechanism": "RAP1 protects against insulin resistance in mice.", "protein": "RAP1", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; telomerase contains glycoprotein subunits.", "mechanism": "Telomerase counteracts telomere shortening, delaying cellular senescence.", "protein": "Telomerase", "protein_enriched": { "function": "Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somati", "gene_name": "TERT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14746" }, "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; SOD1 is a glycoprotein.", "mechanism": "SOD1 reduces oxidative stress, delaying aging.", "protein": "SOD1", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; SOD2 is a glycoprotein.", "mechanism": "SOD2 reduces mitochondrial oxidative stress, delaying aging.", "protein": "SOD2", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; CAT is a glycoprotein.", "mechanism": "CAT detoxifies hydrogen peroxide, reducing oxidative damage and aging.", "protein": "CAT", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not specified in article; GPx is a glycoprotein.", "mechanism": "GPx removes lipid peroxides, reducing oxidative stress and aging.", "protein": "GPx", "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Not specified in article.", "mechanism": "ATG2 is essential for autophagy; its loss shortens lifespan.", "protein": "ATG2", "protein_enriched": { "function": "Lipid transfer protein involved in autophagosome assembly (PubMed:28561066, PubMed:30952800, PubMed:31271352). Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and med", "gene_name": "ATG2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q2TAZ0" }, "relationship_type": "protective", "source_pmcid": "PMC11200722" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Non-enzymatic glycation of hemoglobin N-terminal valine.", "mechanism": "Reflects chronic hyperglycemia; reduced by chokeberry intervention.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Insulin levels indicate insulin resistance; stabilized by chokeberry fiber.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation modulates LDL receptor binding.", "mechanism": "LDL levels reduced by chokeberry juice/fiber; lowers cardiovascular risk.", "protein": "LDL Cholesterol (ApoB-100)", "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation essential for secretion and function.", "mechanism": "CRP is an acute-phase glycoprotein; not significantly changed by intervention.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Liver Disease", "glycan_involvement": "N-glycosylation affects enzyme stability.", "mechanism": "AST levels decreased by chokeberry fiber; marker of liver injury.", "protein": "Aspartate Transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Liver Disease", "glycan_involvement": "N-glycosylation influences enzyme activity.", "mechanism": "ALT levels reduced by chokeberry juice; marker of hepatic function.", "protein": "Alanine Transaminase (ALT)", "protein_enriched": { "function": "Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule", "gene_name": "rub", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24297" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "low", "disease": "Liver Disease", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "GGTP levels unchanged; marker of liver and biliary tract disorders.", "protein": "Gamma-glutamyltransferase (GGTP)", "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Oxidative Stress-related Disorders", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "SOD activity increased by chokeberry; protects against ROS.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11200734" }, { "confidence": "medium", "disease": "Oxidative Stress-related Disorders", "glycan_involvement": "Glycosylation affects stability and activity.", "mechanism": "Activity increased by chokeberry; detoxifies peroxides.", "protein": "Glutathione Peroxidase", "relationship_type": "protective", "source_pmcid": "PMC11200734" }, { "confidence": "low", "disease": "Metabolic Syndrome", "glycan_involvement": "N-glycosylation required for transporter function.", "mechanism": "Uric acid levels modulated by chokeberry; associated with metabolic syndrome.", "protein": "Uric Acid Transporters (e.g., SLC22A12)", "protein_enriched": { "function": "Involved in amino acid permease processing and required for the efficient translocation of structurally related amino acid permeases from the endoplasmic reticulum to the plasma membrane", "gene_name": "psh3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y876" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200734" }, { "confidence": "high", "disease": "Porcine Cytomegalovirus Infection", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Glycoprotein B is used as a diagnostic antigen for PCMV infection via ELISA and Western blot.", "protein": "Glycoprotein B (PCMV)", "relationship_type": "biomarker", "source_pmcid": "PMC11200752" }, { "confidence": "high", "disease": "Postweaning Multisystemic Wasting Syndrome (PMWS)", "glycan_involvement": "Glycosylation may modulate immune evasion and host response.", "mechanism": "PCV2 capsid protein is essential for viral infection and pathogenesis of PMWS.", "protein": "Capsid Protein (PCV2)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "medium", "disease": "Porcine Dermatitis and Nephropathy Syndrome (PDNS)", "glycan_involvement": "Glycosylation may affect tissue tropism.", "mechanism": "PCV2 capsid protein is implicated in PDNS pathogenesis.", "protein": "Capsid Protein (PCV2)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "high", "disease": "Porcine Reproductive Failure", "glycan_involvement": "Capsid glycosylation may influence vertical transmission.", "mechanism": "PPV capsid proteins mediate infection leading to fetal death and mummification.", "protein": "Capsid Proteins VP1/VP2/VP3 (PPV)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "medium", "disease": "Post-Transplant Lymphoproliferative Disease (PTLD)", "glycan_involvement": "Glycosylation may affect lymphocyte tropism.", "mechanism": "PLHV-1 glycoprotein B is associated with PTLD in miniature pig models.", "protein": "Glycoprotein B (PLHV-1)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "high", "disease": "Hepatitis E (human)", "glycan_involvement": "Glycosylation modulates immunogenicity.", "mechanism": "HEV capsid protein is used for serological diagnosis and is the main antigen in ELISA.", "protein": "Capsid Protein (HEV)", "relationship_type": "biomarker", "source_pmcid": "PMC11200752" }, { "confidence": "high", "disease": "Porcine Reproductive and Respiratory Syndrome (PRRS)", "glycan_involvement": "Glycosylation is critical for infectivity and immune escape.", "mechanism": "PRRSV envelope glycoproteins mediate host cell entry and immune evasion.", "protein": "Envelope Glycoprotein (PRRSV)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "medium", "disease": "Porcine Dermatitis and Nephropathy Syndrome (PDNS)", "glycan_involvement": "Potential role in immune modulation.", "mechanism": "PCV3 capsid protein is implicated in PDNS and other systemic inflammatory diseases.", "protein": "Capsid Protein (PCV3)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "medium", "disease": "Porcine Reproductive Failure", "glycan_involvement": "Possible involvement in vertical transmission.", "mechanism": "PCV3 capsid protein associated with reproductive failure and congenital tremors.", "protein": "Capsid Protein (PCV3)", "relationship_type": "causal", "source_pmcid": "PMC11200752" }, { "confidence": "medium", "disease": "Porcine Cytomegalovirus Infection", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "MCP is used for phylogenetic analysis and diagnosis of PCMV infection.", "protein": "Major Capsid Protein (PCMV)", "relationship_type": "biomarker", "source_pmcid": "PMC11200752" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation of ICAM-1 is essential for its cell surface localization and function.", "mechanism": "Sulforaphane suppresses ICAM-1 expression, reducing leukocyte adhesion and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "VCAM-1 glycosylation modulates its adhesive properties.", "mechanism": "Sulforaphane inhibits VCAM-1 expression, decreasing leukocyte recruitment to inflamed tissue.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200786" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "E-selectin binds to sialylated glycan ligands on leukocytes.", "mechanism": "Sulforaphane reduces E-selectin expression, limiting eosinophil and neutrophil migration.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation affects NF-\u03baB subunit stability and nuclear translocation.", "mechanism": "NF-\u03baB activation drives pro-inflammatory cytokine expression; sulforaphane inhibits NF-\u03baB signaling.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Nrf2 glycosylation may regulate its stability and activity.", "mechanism": "Sulforaphane activates Nrf2, upregulating antioxidant genes and reducing renal inflammation.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Pulmonary fibrosis", "glycan_involvement": "TNF-\u03b1 glycosylation is important for secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes fibrosis; sulforaphane suppresses TNF-\u03b1 production.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11200786" }, { "confidence": "medium", "disease": "Sickle cell disease", "glycan_involvement": "IL-6 glycosylation affects its stability and activity.", "mechanism": "IL-6 is elevated in sickle cell inflammation; sulforaphane reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "IL-1\u03b2 glycosylation modulates secretion and receptor interaction.", "mechanism": "IL-1\u03b2 drives colonic inflammation; sulforaphane inhibits IL-1\u03b2 expression.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "COX-2 glycosylation affects enzyme activity and localization.", "mechanism": "COX-2 mediates inflammatory prostaglandin synthesis; sulforaphane suppresses COX-2 expression.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200786" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "iNOS glycosylation influences enzyme stability and activity.", "mechanism": "iNOS-derived nitric oxide promotes tumor progression; sulforaphane inhibits iNOS expression.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC11200786" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Leptin is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Elevated serum leptin distinguishes ALF from ACLF/dACLD; low leptin excludes ALF.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200812" }, { "confidence": "high", "disease": "Acute-on-Chronic Liver Failure (ACLF)", "glycan_involvement": "Glycosylation affects leptin's bioactivity and receptor binding.", "mechanism": "Lower serum leptin in ACLF compared to ALF; not useful for positive diagnosis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200812" }, { "confidence": "medium", "disease": "Decompensated Advanced Chronic Liver Disease (dACLD)", "glycan_involvement": "Glycosylation status may affect circulating levels.", "mechanism": "Serum leptin similar to healthy controls; not elevated as in ALF.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200812" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)", "glycan_involvement": "Glycosylation required for leptin's receptor interaction.", "mechanism": "Leptin stimulates hepatic inflammation and fibrogenesis via GATA3/NF-\u03baB signaling.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11200812" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Steatohepatitis (MASH)", "glycan_involvement": "Therapeutic leptin requires proper glycosylation for efficacy.", "mechanism": "Leptin therapy used in lipodystrophy, MASLD, and MASH to improve metabolic function.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11200812" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation modulates leptin's stability and activity.", "mechanism": "Leptin necessary for development of hepatic fibrosis after chronic injury.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11200812" }, { "confidence": "low", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Glycosylation may influence leptin's tumor-promoting activity.", "mechanism": "Elevated leptin associated with oncogenic effects in liver.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11200812" }, { "confidence": "low", "disease": "Alcoholic Liver Injury", "glycan_involvement": "Glycosylation required for leptin's function.", "mechanism": "Leptin involved in inflammatory and fibrogenic processes in alcoholic liver injury.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11200812" }, { "confidence": "low", "disease": "Chronic Viral Hepatitis", "glycan_involvement": "Glycosylation affects leptin's immune signaling.", "mechanism": "Leptin implicated in pathogenesis via immune modulation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11200812" }, { "confidence": "medium", "disease": "Liver Regeneration (after hepatectomy/ALF)", "glycan_involvement": "Glycosylation essential for leptin's regenerative signaling.", "mechanism": "Leptin promotes liver regeneration; deficiency impairs recovery.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "protective", "source_pmcid": "PMC11200812" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "KL-6 is a mucin-type glycoprotein; its glycosylation is essential for its detection and function as a biomarker.", "mechanism": "KL-6 is highly expressed in type II alveolar and bronchial epithelial cells in ILD, correlating with disease severity and progression.", "protein": "KL-6", "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "medium", "disease": "Respiratory Failure (RF)", "glycan_involvement": "Glycosylation of KL-6 modulates its interaction with fibroblasts.", "mechanism": "Elevated KL-6 promotes fibroblast migration/proliferation, leading to restrictive ventilation dysfunction and RF.", "protein": "KL-6", "relationship_type": "causal", "source_pmcid": "PMC11200819" }, { "confidence": "medium", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and receptor binding.", "mechanism": "IL-6 promotes migration and proliferation of pulmonary fibroblasts, contributing to fibrosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11200819" }, { "confidence": "low", "disease": "Respiratory Failure (RF)", "glycan_involvement": "Albumin glycosylation status may affect its half-life and function.", "mechanism": "Low albumin levels reflect malnutrition and inflammation, associated with increased RF risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "medium", "disease": "Respiratory Failure (RF)", "glycan_involvement": "Prothrombin is N-glycosylated, which affects its secretion and activity.", "mechanism": "Prolonged prothrombin time indicates coagulation dysfunction, associated with RF risk in AECOPD.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "medium", "disease": "Acute Exacerbation of COPD (AECOPD)", "glycan_involvement": "Cell surface glycoproteins mediate immune cell trafficking and activation.", "mechanism": "Elevated WBC count indicates infection/inflammation, a trigger for AECOPD and RF.", "protein": "White blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "low", "disease": "Respiratory Failure (RF)", "glycan_involvement": "HbA1c is a glycated protein, not a classical glycoprotein.", "mechanism": "Elevated HbA1c reflects poor glycemic control, associated with increased RF risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "low", "disease": "Heart Failure (HF)", "glycan_involvement": "LDL glycosylation affects its clearance and receptor binding.", "mechanism": "Altered LDL levels may reflect metabolic disturbances in HF.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "low", "disease": "Heart Failure (HF)", "glycan_involvement": "HDL glycosylation affects its anti-inflammatory properties.", "mechanism": "Altered HDL levels may reflect metabolic disturbances in HF.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "medium", "disease": "Acute Exacerbation of COPD (AECOPD)", "glycan_involvement": "Glycosylation is required for KL-6 detection in serum.", "mechanism": "KL-6 may be elevated in AECOPD with ILD overlap, indicating worse prognosis.", "protein": "KL-6", "relationship_type": "biomarker", "source_pmcid": "PMC11200819" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is a glycoprotein; glycosylation may affect aggregation and clearance.", "mechanism": "Aggregation into plaques in brain tissue is a hallmark of AD pathology.", "protein": "Amyloid-\u03b2 peptide (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC11201003" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; glycosylation may modulate aggregation propensity.", "mechanism": "Hyperphosphorylated Tau forms neurofibrillary tangles, contributing to neuronal dysfunction.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC11201003" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "HIF3A is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Circadian rhythm disruption increases m6A methylation at Hif3\u03b1 site 3632, upregulating HIF3A and accelerating AD progression.", "protein": "HIF3A", "relationship_type": "causal", "source_pmcid": "PMC11201003" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "KDM3A is glycosylated; glycosylation may regulate activity.", "mechanism": "KDM3A expression decreases as HIF3A increases; KDM3A has protective roles in neuroinflammation and hypoxia.", "protein": "KDM3A", "relationship_type": "protective", "source_pmcid": "PMC11201003" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation is essential for secretion and activity.", "mechanism": "TGF-\u03b21 expression decreases with increased HIF3A; TGF-\u03b21 modulates neuroinflammation and cellular protection.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective", "source_pmcid": "PMC11201003" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect HIF3A stability under hypoxic conditions.", "mechanism": "Upregulated HIF3A is associated with hypoxia response and inflammation post-stroke.", "protein": "HIF3A", "relationship_type": "biomarker", "source_pmcid": "PMC11201003" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation may modulate KDM3A function in hypoxia.", "mechanism": "KDM3A contributes to neuroprotection in hypoxic brain injury.", "protein": "KDM3A", "relationship_type": "protective", "source_pmcid": "PMC11201003" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation is required for TGF-\u03b21 activity.", "mechanism": "TGF-\u03b21 aids in neuroprotection and anti-inflammatory responses post-stroke.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective", "source_pmcid": "PMC11201003" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may influence HIF3A's role in cancer.", "mechanism": "HIF3A anomalies linked to tumor progression and angiogenesis.", "protein": "HIF3A", "relationship_type": "biomarker", "source_pmcid": "PMC11201003" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation critical for TGF-\u03b21 function in cancer.", "mechanism": "TGF-\u03b21 regulates cellular transformation, fibrosis, and tumor progression.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201003" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation regulates Fas receptor surface expression and ligand binding.", "mechanism": "Fas receptor mediates extrinsic apoptosis; targeting Fas can induce programmed cell death in lung cancer cells.", "protein": "Fas (CD95)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation affects receptor stability and ligand interaction.", "mechanism": "TNF receptor activation triggers extrinsic apoptosis; modulating TNFR signaling can enhance cell death in lung cancer.", "protein": "TNF Receptor (TNFRSF1A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation modulates receptor clustering and apoptotic signaling.", "mechanism": "TRAIL receptors induce apoptosis in cancer cells; agonists can overcome resistance.", "protein": "TRAIL Receptor (DR4/DR5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may affect Bcl-2 localization and stability.", "mechanism": "Overexpression of Bcl-2 confers resistance to apoptosis and promotes tumor survival.", "protein": "Bcl-2", "relationship_type": "causal", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may regulate mitochondrial targeting.", "mechanism": "Bcl-xL inhibits apoptosis, contributing to therapy resistance.", "protein": "Bcl-xL", "relationship_type": "causal", "source_pmcid": "PMC11201027" }, { "confidence": "medium", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "CRP glycosylation affects its immunological activity.", "mechanism": "CRP levels are modulated by omega-3 fatty acids, reflecting inflammation status.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "EGFR glycosylation regulates ligand binding and receptor activation.", "mechanism": "EGFR signaling promotes proliferation; resveratrol and its analogs inhibit EGFR, inducing apoptosis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Potential glycosylation may regulate activity (not directly shown in article).", "mechanism": "ULK1 promotes autophagy; targeting ULK1 can modulate autophagic cell death.", "protein": "ULK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "No direct glycosylation, but interacts with glycoproteins in autophagosomes.", "mechanism": "LC3 is a marker of autophagy flux; altered LC3 levels indicate autophagy status in lung cancer.", "protein": "LC3", "relationship_type": "biomarker", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Therapy resistance in lung cancer", "glycan_involvement": "Glycosylation impacts receptor function and sensitivity to TRAIL.", "mechanism": "Restoring TRAIL receptor function can overcome resistance to apoptosis-inducing therapies.", "protein": "TRAIL Receptor (DR4/DR5)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201027" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation required for cell surface localization and ligand binding.", "mechanism": "uPAR overexpression promotes tumor invasion, metastasis, angiogenesis, and multidrug resistance.", "protein": "uPAR", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201033" }, { "confidence": "high", "disease": "Sepsis (including viral sepsis/COVID-19)", "glycan_involvement": "Glycosylation stabilizes suPAR in circulation.", "mechanism": "Elevated suPAR in plasma correlates with severity and prognosis in sepsis and COVID-19.", "protein": "suPAR", "relationship_type": "biomarker", "source_pmcid": "PMC11201033" }, { "confidence": "high", "disease": "Cardiovascular disease (atherosclerosis, ACS, AMI, heart failure)", "glycan_involvement": "Glycosylation essential for receptor function and interactions.", "mechanism": "uPAR expression on immune and endothelial cells drives inflammation, plaque instability, and predicts adverse events.", "protein": "uPAR", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201033" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation maintains suPAR stability and detection in plasma.", "mechanism": "suPAR levels reflect chronic innate immune activation and correlate with disease risk.", "protein": "suPAR", "relationship_type": "biomarker", "source_pmcid": "PMC11201033" }, { "confidence": "high", "disease": "Acute ischemic stroke", "glycan_involvement": "Glycosylation required for receptor-ligand interactions.", "mechanism": "uPAR levels correlate with carotid plaque burden and stroke risk; uPA used as thrombolytic.", "protein": "uPAR", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201033" }, { "confidence": "medium", "disease": "Viral myocarditis", "glycan_involvement": "Glycosylation supports cell surface expression and immune interactions.", "mechanism": "uPAR mediates inflammatory cell infiltration and cardiac remodeling after viral infection.", "protein": "uPAR", "relationship_type": "causal", "source_pmcid": "PMC11201033" }, { "confidence": "medium", "disease": "Congenital heart block", "glycan_involvement": "Glycosylation necessary for receptor function.", "mechanism": "uPAR involved in phagocytic clearance of apoptotic cardiomyocytes, contributing to fibrosis and heart block.", "protein": "uPAR", "relationship_type": "causal", "source_pmcid": "PMC11201033" }, { "confidence": "medium", "disease": "Leukemia (AML)", "glycan_involvement": "Glycosylation affects receptor stability and function.", "mechanism": "uPAR mRNA variants and protein promote cell adhesion, migration, and pro-tumoral signaling.", "protein": "uPAR", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11201033" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation supports receptor-ligand interactions.", "mechanism": "uPAR required for Serp-1 immune-modulating anti-tumor effects; high uPAR expression in tumors.", "protein": "uPAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201033" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation modulates ECM interactions.", "mechanism": "Vitronectin interacts with uPAR to promote cell adhesion, migration, and tumor invasion.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "causal", "source_pmcid": "PMC11201033" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "AST is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "Elevated serum AST is indicative of hepatocyte injury and is used in the HSI index for NAFLD diagnosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "ALT glycosylation may influence its secretion and activity.", "mechanism": "Elevated ALT reflects liver cell damage and is a key component of the HSI index for NAFLD prediction.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Albumin is N-glycosylated, affecting its stability and transport.", "mechanism": "Serum albumin levels are used in laboratory panels for NAFLD assessment; low levels may indicate advanced liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "ALP glycosylation modulates its enzymatic activity and serum levels.", "mechanism": "Elevated ALP may indicate cholestasis or liver dysfunction, included in NAFLD laboratory panels.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "GGT glycosylation affects its stability and function.", "mechanism": "Elevated GGT is associated with oxidative stress and liver injury in NAFLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect AST clearance and detection.", "mechanism": "Progression from NAFLD to fibrosis is marked by increasing AST levels.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may influence ALT serum levels.", "mechanism": "ALT elevation is associated with ongoing liver injury and fibrosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis affects albumin function.", "mechanism": "Decreased albumin is a marker of advanced liver disease and cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect AST detection in cancer.", "mechanism": "Chronic elevation of AST is associated with progression to HCC in NAFLD patients.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates GGT activity in cancer.", "mechanism": "Elevated GGT is linked to oxidative stress and risk of HCC.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201081" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Restoration of circulating adiponectin levels associated with improved metabolic and cytoprotective effects in NASH patients treated with UDCA/Vitamin E.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11201095" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "Pro-inflammatory cytokine elevated in MAFLD; reduced by antioxidants (Vitamin E, Silybin, Vitamin D) and lifestyle interventions.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201095" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Key mediator of hepatic stellate cell activation and collagen secretion; reduced by Vitamin E and other antioxidants.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "Involved in extracellular matrix remodeling; decreased by Vitamin E and antioxidant therapy.", "protein": "MMP2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects fibril formation.", "mechanism": "Major collagen component in fibrotic liver; expression reduced by Vitamin E and silybin.", "protein": "Col1a1", "relationship_type": "biomarker", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation required for inhibitory function.", "mechanism": "Inhibitor of MMPs, elevated in fibrosis; reduced by Vitamin E and silybin.", "protein": "TIMP1", "relationship_type": "biomarker", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may affect stability.", "mechanism": "Marker of ER stress; reduced by Vitamin E, indicating decreased oxidative and ER stress.", "protein": "CHOP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "N-glycosylation required for chaperone activity.", "mechanism": "ER chaperone upregulated in stress; reduced by Vitamin E, indicating improved ER function.", "protein": "BiP", "protein_enriched": { "function": "Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Inv", "gene_name": "HSPA5", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P11021" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201095" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation affects folding activity.", "mechanism": "ER chaperone involved in protein folding; reduced by Vitamin E, indicating reduced ER stress.", "protein": "PDI", "relationship_type": "biomarker", "source_pmcid": "PMC11201095" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Glycosylation may affect nuclear translocation.", "mechanism": "Master regulator of antioxidant response; activation by Vitamin D, Silybin, and EVOO improves oxidative stress and liver pathology.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201095" }, { "confidence": "high", "disease": "Inherited thrombophilia", "glycan_involvement": "Protein S is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Protein S deficiency leads to impaired anticoagulation, increasing thrombosis risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Inherited thrombophilia", "glycan_involvement": "Protein C is a glycoprotein; glycosylation is important for secretion and activity.", "mechanism": "Protein C deficiency impairs anticoagulant pathway, predisposing to thrombosis.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Inherited thrombophilia", "glycan_involvement": "Antithrombin is a glycoprotein; glycosylation modulates heparin binding and function.", "mechanism": "Antithrombin deficiency reduces inhibition of coagulation proteases, increasing thrombosis risk.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are central to APS pathogenesis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11201097" }, { "confidence": "medium", "disease": "Obstetric morbidity (APOs)", "glycan_involvement": "Glycosylation may affect protein S levels during pregnancy.", "mechanism": "Protein S deficiency (inherited or acquired) is associated with increased risk of APOs.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "medium", "disease": "Obstetric morbidity (APOs)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Protein C deficiency is linked to adverse pregnancy outcomes.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Recurrent miscarriage", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Anti-beta-2 glycoprotein I antibodies contribute to recurrent miscarriage in APS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Thrombotic events (venous/arterial)", "glycan_involvement": "Glycosylation affects half-life and function.", "mechanism": "Deficiency increases risk of thrombosis, especially in prothrombotic states like pregnancy.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation influences antibody binding.", "mechanism": "Anti-beta-2 glycoprotein I antibodies implicated in placental dysfunction.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Thrombotic events (venous/arterial)", "glycan_involvement": "Glycosylation critical for anticoagulant activity.", "mechanism": "Deficiency increases risk of thrombosis.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC11201097" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "N-glycosylation modulates antigenicity and immune recognition.", "mechanism": "Autoantigen targeted by immune response leading to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "N-glycosylation affects immunogenicity and disease induction.", "mechanism": "Immunization with MOG peptide induces EAE, mimicking MS pathology.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation influences cytokine stability and receptor interaction.", "mechanism": "Upregulated in neuroinflammation; blockade worsens MS.", "protein": "Tumor Necrosis Factor-alpha (TNF\u03b1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Elevated in active lesions; drives Th1-mediated inflammation.", "protein": "Interferon gamma (IFN\u03b3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201189" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation affects cytokine function.", "mechanism": "Th17 cytokine involved in severe EAE and MS; less prominent in mild EAE.", "protein": "Interleukin-17 (IL-17)", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:18025225, PubMed:19144317, PubMed:26431948). Signals via IL17R", "gene_name": "Il17a", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q62386" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201189" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "PLP immunization induces EAE without PTx, modeling MS.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "causal", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation affects GPCR trafficking and function.", "mechanism": "CB1 expression required for cannabinoid-mediated suppression of EAE.", "protein": "Cannabinoid Receptor 1 (CB1)", "protein_enriched": { "function": "G-protein coupled receptor for cannabinoids, including endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (PubMed:22388959, P", "gene_name": "Cnr1", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G90784VC" ], "uniprot_id": "P47746" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11201189" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may affect receptor function.", "mechanism": "Knockout exacerbates EAE, suggesting regulatory role.", "protein": "G protein-coupled receptor 141 (GPR141)", "protein_enriched": { "function": "IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts", "gene_name": "Bst2", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G70888PK", "G49108TO" ], "uniprot_id": "Q8R2Q8" }, "relationship_type": "protective", "source_pmcid": "PMC11201189" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation modulates ligand binding and signaling.", "mechanism": "Gi GPCRs mediate immune cell trafficking; druggable targets in MS.", "protein": "Chemokine Receptors (general)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "N-glycosylation of Fc region modulates effector function.", "mechanism": "MOG-specific IgG and IgG1 induced in mild EAE, reflecting B cell involvement.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11201189" }, { "confidence": "high", "disease": "Acute liver failure (ALF)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "A1AT synthesis reflects hepatocyte synthetic function; reduced in ALF.", "protein": "Alpha-1 antitrypsin (A1AT)", "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation affects clotting function.", "mechanism": "Fibrinogen synthesis is impaired in liver failure, contributing to coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "high", "disease": "Acute liver failure (ALF)", "glycan_involvement": "N-glycosylation influences stability and half-life.", "mechanism": "Albumin synthesis is reduced in ALF, indicating impaired liver function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "medium", "disease": "Platelet sequestration", "glycan_involvement": "Glycosylation modulates platelet adhesion.", "mechanism": "CD61 marks platelet accumulation in BEL grafts, contributing to thrombocytopenia.", "protein": "CD61 (Integrin beta-3)", "relationship_type": "causal", "source_pmcid": "PMC11201206" }, { "confidence": "medium", "disease": "Systemic inflammatory response", "glycan_involvement": "Glycosylation affects ligand binding.", "mechanism": "LYVE1 marks lymphatic endothelial cells; its presence indicates immune cell infiltration in grafts.", "protein": "LYVE1", "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "high", "disease": "Systemic inflammatory response", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "IL-6 levels indicate immune activation; not elevated in BEL therapy, suggesting low inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "medium", "disease": "Acute liver failure (ALF)", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "FAH expression marks viable hepatocytes in BEL grafts.", "protein": "FAH (Fumarylacetoacetate hydrolase)", "protein_enriched": { "function": "", "gene_name": "FAH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P16930" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201206" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Endothelial glycoprotein glycans modulate platelet interactions.", "mechanism": "HUVEC reendothelialization reduces platelet activation and clot formation in BEL grafts.", "protein": "Human umbilical vein endothelial cell (HUVEC) glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11201206" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation essential for clot formation.", "mechanism": "Reduced fibrinogen synthesis in liver failure contributes to bleeding and low platelet counts.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11201206" }, { "confidence": "medium", "disease": "Systemic inflammatory response", "glycan_involvement": "Glycosylation required for anti-inflammatory activity.", "mechanism": "A1AT has anti-inflammatory properties; increased synthesis in FH-BEL may reduce inflammation.", "protein": "Alpha-1 antitrypsin (A1AT)", "relationship_type": "protective", "source_pmcid": "PMC11201206" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Leptin is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Promotes cartilage degradation via MMP production, NF-\u03baB, MAPK, and PKC pathways; correlates with OA severity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Resistin is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "Induces matrix degradation via TLR4/CAP1 on chondrocytes, activates NF-\u03baB and cAMP/PKA, promotes inflammation.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "NAMPT is glycosylated; glycosylation may affect activity.", "mechanism": "Elevated in OA; promotes cartilage degradation via IL-6, STAT-3, HIF-2\u03b1, SIRT1/6 pathways.", "protein": "Visfatin (NAMPT)", "protein_enriched": { "function": "Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in ", "gene_name": "NAMPT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43490" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "LCN2 is glycosylated; glycosylation affects stability and function.", "mechanism": "Catabolic effect on chondrocytes and osteoblasts; increases MMPs and ECM destruction.", "protein": "Lipocalin-2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Chemerin is glycosylated; glycosylation affects secretion.", "mechanism": "Increases inflammatory mediators and MMPs in chondrocytes and macrophages; correlates with OA presence.", "protein": "Chemerin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Adiponectin is glycosylated; glycosylation required for multimerization and activity.", "mechanism": "Anti-inflammatory; increases TIMP, decreases MMPs, promotes M2 macrophage polarization.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Progranulin is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "Limits TNF-\u03b1 catabolic effects, increases TNFR2, inhibits \u03b2-catenin pathway, promotes chondroprotection.", "protein": "Progranulin", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11201254" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Vaspin is glycosylated; glycosylation affects stability.", "mechanism": "Promotes chondrocyte survival and differentiation via Akt; lower in OA patients.", "protein": "Vaspin", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Omentin-1 is glycosylated; glycosylation affects receptor binding.", "mechanism": "Promotes M2 macrophage polarization, reduces inflammation and cartilage degradation.", "protein": "Omentin-1", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11201254" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Irisin is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Promotes ECM production, reduces inflammatory cytokines, supports autophagy and mitochondrial function.", "protein": "Irisin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11201254" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "TGR5 is a glycoprotein receptor; glycosylation affects cell surface localization and ligand binding.", "mechanism": "Activation by bile acids improves NAFLD via metabolic regulation.", "protein": "TGR5 (GPBAR1)", "protein_enriched": { "function": "Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macr", "gene_name": "GPBAR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8TDU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Enzyme glycosylation may affect stability and activity.", "mechanism": "HRCC increases Cyp8b1 expression, enhancing bile acid synthesis and improving NAFLD.", "protein": "Cyp8b1", "protein_enriched": { "function": "Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (By similarity). Its targets include: protein kinase B (PKB/AKT1, ", "gene_name": "Pdpk1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O55173" }, "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Enzyme glycosylation may affect stability and activity.", "mechanism": "HRCC reverses MCD-induced suppression of Cyp27a1, increasing bile acid synthesis and reducing hepatic inflammation.", "protein": "Cyp27a1", "protein_enriched": { "function": "UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to facilitate their inactivation and excretion ", "gene_name": "Ugt1a6", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q64435" }, "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect enzyme secretion and activity.", "mechanism": "HRCC increases SOD1 expression, reducing oxidative stress in NAFLD.", "protein": "Superoxide dismutase [Cu-Zn] (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "Sod1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59324HL", "G49108TO" ], "uniprot_id": "P08228" }, "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "HRCC increases GPx1 expression, enhancing antioxidant defense in NAFLD.", "protein": "Glutathione peroxidase-1 (GPx1)", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:10754271, PubMed:21420488, PubMed:36608588, PubMed:9126277, PubMed:919597", "gene_name": "Gpx1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11352" }, "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "HRCC increases catalase expression, reducing ROS and hepatic injury.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycine conjugation is a glycan modification critical for bile acid function.", "mechanism": "Increased GUDCA (via HRCC) improves diabetes and metabolic conditions by regulating bile acid and gut microbiota composition.", "protein": "Glycoursodeoxycholic acid (GUDCA)", "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycine conjugation is a glycan modification critical for bile acid function.", "mechanism": "Increased GUDCA levels (via HRCC) are associated with improved NAFLD outcomes.", "protein": "Glycoursodeoxycholic acid (GUDCA)", "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Bile acid glycosylation/conjugation affects solubility and signaling.", "mechanism": "Increased 23 norDCA (via HRCC) is associated with improved NAFLD, as reduced levels are linked to pediatric NAFLD.", "protein": "23-nor-deoxycholic acid (23 norDCA)", "relationship_type": "protective", "source_pmcid": "PMC11201271" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects receptor function and disease progression.", "mechanism": "Bile acid signaling via TGR5 may impact progression to hepatocellular carcinoma in NAFLD spectrum.", "protein": "TGR5 (GPBAR1)", "protein_enriched": { "function": "Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macr", "gene_name": "GPBAR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8TDU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201271" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CD44v is a heavily glycosylated cell surface protein; glycosylation affects ligand binding and stability.", "mechanism": "CD44v stabilizes SLC7A11, increasing cystine uptake and GSH synthesis, promoting tumor proliferation, invasion, and drug resistance.", "protein": "CD44v", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "SLC7A11 is glycosylated; glycosylation may affect transporter stability and localization.", "mechanism": "Overexpression of SLC7A11 increases cystine uptake and GSH synthesis, conferring resistance to ferroptosis and chemotherapy.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "MRP1 is glycosylated; glycosylation influences trafficking and drug efflux activity.", "mechanism": "MRP1 exports GSH and drug conjugates, contributing to multidrug resistance in tumors.", "protein": "MRP1 (ABCC1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "GPx4 is glycosylated; glycosylation may affect enzyme activity and stability.", "mechanism": "GPx4 uses GSH to reduce lipid peroxides, inhibiting ferroptosis and protecting tumor cells from oxidative damage.", "protein": "GPx4", "relationship_type": "protective", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "GGT is a glycoprotein; glycosylation is essential for its enzymatic activity.", "mechanism": "GGT is upregulated in tumors, facilitating GSH degradation and cysteine supply for tumor growth and redox regulation.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11201279" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "GCL is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "GCL is the rate-limiting enzyme for GSH synthesis; upregulation increases GSH and resistance to oxidative stress and chemotherapy.", "protein": "GCL", "protein_enriched": { "function": "Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis", "gene_name": "GCLC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48506" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "CD44 glycosylation modulates cell adhesion and migration.", "mechanism": "CD44 is highly expressed in gastric cancer stem cells and correlates with poor prognosis and recurrence.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11201279" }, { "confidence": "medium", "disease": "Non-small Cell Lung Cancer", "glycan_involvement": "Glycosylation may regulate SLC7A11 function in lung cancer cells.", "mechanism": "SLC7A11 overexpression leads to lower GSH/GSSG ratio, promoting proliferation and invasiveness.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia", "glycan_involvement": "Glycosylation affects MRP1 drug efflux in leukemia cells.", "mechanism": "MRP1 mediates drug resistance to gemtuzumab ozogamicin; inhibition increases cytotoxicity.", "protein": "MRP1 (ABCC1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201279" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation of CD44v9 influences its cell surface expression and function.", "mechanism": "CD44v9 variant predicts recurrence in early primary gastric cancer.", "protein": "CD44v", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11201279" }, { "confidence": "high", "disease": "Cholelithiasis", "glycan_involvement": "Heavy O-glycosylation in PTS domain increases resistance to proteases and gel formation.", "mechanism": "Acts as a pronucleating agent, forms gel matrix for stone nucleation and growth.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Cholelithiasis", "glycan_involvement": "O-glycosylation enables multimerization and high viscosity.", "mechanism": "Promotes nucleation and growth of cholesterol and pigment stones via viscous gel formation.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Pigment gallstones", "glycan_involvement": "O-glycosylation increases gel viscosity and stone matrix formation.", "mechanism": "Upregulated in inflamed gallbladder epithelium, associated with pigment stone formation.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Brown pigment stones", "glycan_involvement": "O-glycosylation facilitates gel and crystal nucleation.", "mechanism": "Higher mucin content in gallbladders with brown pigment stones; acts as main matrix.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Brown pigment stones", "glycan_involvement": "Anionic glycoprotein structure promotes crystal aggregation.", "mechanism": "Bacterial glycocalyx acts as conjugating agent for calcium bilirubinate crystal aggregation.", "protein": "Bacterial glycocalyx", "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "medium", "disease": "Brown pigment stones", "glycan_involvement": "Enzyme activity, glycosylation not specified.", "mechanism": "Hydrolyzes conjugated bilirubin, increasing unconjugated bilirubin for stone formation.", "protein": "Endogenous \u03b2-glucuronidase", "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Hepatolithiasis", "glycan_involvement": "O-glycosylation increases viscosity and stone matrix formation.", "mechanism": "Chronic inflammation and bacterial infection upregulate mucin secretion, promoting stone formation.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "O-glycosylation increases gel viscosity.", "mechanism": "Excessive mucin secretion increases bile viscosity, impairs flow, and promotes cholestasis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "medium", "disease": "Chronic proliferative cholangitis", "glycan_involvement": "O-glycosylation supports mucin gel formation.", "mechanism": "Upregulated in biliary epithelium during chronic inflammation, correlates with stone formation.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201413" }, { "confidence": "medium", "disease": "Brown pigment stones", "glycan_involvement": "Enzyme activity, glycosylation not specified.", "mechanism": "Hydrolyzes conjugated bilirubin, facilitating calcium bilirubinate stone formation.", "protein": "Bacterial \u03b2-glucuronidase", "relationship_type": "causal", "source_pmcid": "PMC11201413" }, { "confidence": "medium", "disease": "Endoleak", "glycan_involvement": "N-glycosylation affects fibrinogen's stability and function in coagulation.", "mechanism": "Higher fibrinogen levels observed in patients with endoleak post-EVAR.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "AAA growth/expansion", "glycan_involvement": "N-glycosylation modulates haptoglobin's binding to hemoglobin and immune functions.", "mechanism": "Hp 2-1 phenotype associated with faster AAA expansion; glycosylation affects hemoglobin binding and immune modulation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "Post-surgical mortality", "glycan_involvement": "N-glycosylation influences albumin's stability and vascular effects.", "mechanism": "Low albumin levels predict higher 30-day and 1-year mortality after AAA surgery.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "AAA incidence and growth/expansion", "glycan_involvement": "CRP is heavily glycosylated, which affects its immune recognition and clearance.", "mechanism": "Elevated CRP correlates with AAA incidence and faster expansion rates.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "AAA growth/expansion", "glycan_involvement": "N-glycosylation modulates C5a's inflammatory activity.", "mechanism": "Elevated C5a levels correlate with increased AAA diameter over 6 months.", "protein": "Complement Factor C5a", "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "medium", "disease": "AAA (post-surgical monitoring)", "glycan_involvement": "N-glycosylation and GPI-anchor affect suPAR's cell surface expression and shedding.", "mechanism": "suPAR levels increase post-EVAR, reflecting inflammation and disease severity.", "protein": "Soluble Urokinase Plasminogen Activator Receptor (suPAR)", "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "AAA growth/expansion and endoleak", "glycan_involvement": "N-glycosylation regulates MMP9 secretion and activity.", "mechanism": "Elevated MMP9 and proMMP9 levels associated with AAA growth and late endoleak.", "protein": "Matrix Metalloproteinase 9 (MMP9)", "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "medium", "disease": "AAA growth/expansion", "glycan_involvement": "N-glycosylation affects collagen's ECM interactions and stability.", "mechanism": "Higher circulating type XVIII collagen associated with increased AAA expansion rate.", "protein": "Type XVIII Collagen", "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "medium", "disease": "AAA growth/expansion", "glycan_involvement": "Derived from glycosylated type XVIII collagen; glycosylation may affect anti-angiogenic activity.", "mechanism": "Elevated endostatin levels significantly associated with aortic expansion.", "protein": "Endostatin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "medium", "disease": "AAA growth/expansion", "glycan_involvement": "N-glycosylation modulates MFAP4's ECM binding and stability.", "mechanism": "Higher MFAP4 levels negatively correlate with AAA growth rate and risk of surgical repair.", "protein": "Microfibrillar-Associated Protein 4 (MFAP4)", "protein_enriched": { "function": "Bone marrow-derived monocyte and paracrine-acting protein that promotes cardiac myocyte survival and adaptive angiogenesis for cardiac protection and/or repair after myocardial infarction (MI). Stimul", "gene_name": "MYDGF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q969H8" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC11201473" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects aggregation and clearance.", "mechanism": "A\u03b2 activates NLRP3 inflammasome, leading to neuroinflammation and neuronal pyroptosis.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11201480" }, { "confidence": "medium", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Glycosylation of APP influences A\u03b2 production and deposition.", "mechanism": "A\u03b2 in perilymph may link brain neurodegeneration to cochlear damage and SNHL.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201480" }, { "confidence": "high", "disease": "Vestibular schwannoma", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation modulates receptor binding and stability.", "mechanism": "TNF-\u03b1 in perilymph activates NLRP3, causing cochlear inflammation and SNHL.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201480" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and activity.", "mechanism": "Elevated TNF-\u03b1 predicts MS relapses and may mediate neuroinflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201480" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; NLRP3 activation is downstream of glycoprotein signaling.", "mechanism": "NLRP3 activation by A\u03b2 leads to IL-1\u03b2/IL-18 release and neuronal death.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11201480" }, { "confidence": "high", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Indirect; inflammasome activation involves glycoprotein cytokines.", "mechanism": "NLRP3 mutation/activation induces cochlear inflammation and SNHL.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC11201480" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 released via NLRP3 activation promotes neuroinflammation and neuronal death.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201480" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "IL-18 is glycosylated; glycosylation modulates activity.", "mechanism": "IL-18 released via NLRP3 activation promotes neuroinflammation and pyroptosis.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11201480" }, { "confidence": "medium", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Connexins are glycoproteins; glycosylation affects channel function.", "mechanism": "Altered connexin expression disrupts cochlear homeostasis, contributing to SNHL.", "protein": "Connexins (Cxs)", "relationship_type": "causal", "source_pmcid": "PMC11201480" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "CXCL13 is glycosylated; glycosylation modulates chemokine activity.", "mechanism": "Elevated CXCL13 in CSF/perilymph reflects neuroinflammation in MS.", "protein": "CXCL13", "relationship_type": "biomarker", "source_pmcid": "PMC11201480" }, { "confidence": "high", "disease": "Neurotrophic Keratitis", "glycan_involvement": "NGF is a glycoprotein; glycosylation affects folding and stability, enabling therapeutic use.", "mechanism": "Promotes corneal epithelial healing via TrkA and p75NTR signaling.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may influence NGF stability and receptor interaction.", "mechanism": "Supports cholinergic neuron survival and function in CNS.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation impacts NGF bioactivity and delivery.", "mechanism": "Promotes neuronal survival and functional improvement.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "high", "disease": "Hereditary Sensory and Autonomic Neuropathy type V (HSAN V)", "glycan_involvement": "Altered glycosylation may affect NGF processing and secretion.", "mechanism": "Mutations in NGF gene disrupt NGF/proNGF balance, causing insensitivity to pain.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "causal", "source_pmcid": "PMC11201509" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation affects NGF stability and immune recognition.", "mechanism": "NGF upregulated in inflammation; anti-NGF antibodies reduce pain.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation required for NGF folding and secretion.", "mechanism": "Accelerates wound healing and reduces pain in vasculitic ulcers.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "high", "disease": "Diabetic Ulcers/Wound Healing", "glycan_involvement": "Glycosylation critical for NGF activity in tissue repair.", "mechanism": "Stimulates keratinocyte and fibroblast proliferation via Akt/mTOR pathway.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "Optic Glioma", "glycan_involvement": "Glycosylation ensures NGF stability for clinical use.", "mechanism": "Improves visual function and neural recovery without promoting tumor growth.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "HIV-associated Sensory Neuropathy", "glycan_involvement": "Glycosylation affects NGF pharmacokinetics and efficacy.", "mechanism": "Restores sensory neuron function and reduces neuropathic pain.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "medium", "disease": "Diabetic Neuropathy", "glycan_involvement": "Glycosylation impacts NGF stability and delivery.", "mechanism": "Intended to improve nerve function; clinical efficacy not demonstrated.", "protein": "Nerve Growth Factor (NGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201509" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect stability and activity in brain tissue.", "mechanism": "Catalase reduces oxidative stress and beta-amyloid accumulation, protecting neurons.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201554" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may modulate mitochondrial/peroxisomal localization.", "mechanism": "Catalase neutralizes H2O2, reducing dopaminergic neuron loss due to oxidative stress.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201554" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may influence circulatory stability and tissue targeting.", "mechanism": "Catalase prevents ROS-induced endothelial dysfunction and atherosclerosis.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC11201554" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Altered glycosylation may affect enzyme activity in diabetic tissues.", "mechanism": "Catalase activity is reduced in diabetes, contributing to oxidative damage and beta-cell dysfunction.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201554" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect immune cell interactions.", "mechanism": "Catalase modulates oxidative stress in synovial tissue, influencing inflammation and joint damage.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201554" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation may impact mucosal stability and immune modulation.", "mechanism": "Catalase activity in T cells regulates apoptosis and mucosal inflammation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC11201554" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect tumor microenvironment interactions.", "mechanism": "Catalase protects normal cells from ROS but may support cancer cell survival; regulates apoptosis.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11201554" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease", "glycan_involvement": "Glycosylation may influence airway epithelial stability.", "mechanism": "Catalase reduces oxidative stress in lung tissue, mitigating inflammation and damage.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11201554" }, { "confidence": "medium", "disease": "Hepatic disease", "glycan_involvement": "Glycosylation may affect hepatic targeting and enzyme stability.", "mechanism": "Catalase preserves liver redox balance and protects against fatty liver and hepatic injury.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC11201554" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may impact renal localization and activity.", "mechanism": "Catalase maintains renal redox balance, protecting against oxidative damage.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11201554" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "RPN1 is a key subunit of OST complex for N-linked glycosylation; its loss reduces glycosylation, increases ER stress, and affects cell death.", "mechanism": "RPN1 knockdown increases proliferation and invasion of liver cancer cells; RPN1 regulates N-glycosylation and ER stress.", "protein": "RPN1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Reduced N-glycosylation leads to protein misfolding and ER stress.", "mechanism": "RPN1 knockdown activates ER stress, inhibits proliferation/invasion, and promotes apoptosis in breast cancer cells.", "protein": "RPN1", "relationship_type": "causal", "source_pmcid": "PMC11201601" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "Indirect; SLC7A11 affects cystine uptake and redox balance, impacting glycoprotein folding.", "mechanism": "Overexpression of SLC7A11 induces disulfidptosis under glucose deprivation, leading to cell death.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "causal", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Pan-cancer", "glycan_involvement": "Glycosylation may affect cytoskeletal function and immune modulation.", "mechanism": "ACTB overexpression correlates with immune infiltration and tumor invasion.", "protein": "ACTB", "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Uterine cancer", "glycan_involvement": "Mutations may alter glycosylation and cytoskeletal interactions.", "mechanism": "High mutation frequency in FLNA correlates with prognosis.", "protein": "FLNA", "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Potential impact on glycosylation affecting contractile function.", "mechanism": "MYH11 downregulation observed in bladder cancer tissues.", "protein": "MYH11", "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "Glycosylation may regulate protein stability and stemness.", "mechanism": "LRPPRC expression positively correlates with tumor stemness and poor prognosis.", "protein": "LRPPRC", "protein_enriched": { "function": "May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are po", "gene_name": "LRPPRC", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G13193DT", "G49108TO" ], "uniprot_id": "P42704" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "low", "disease": "Pan-cancer", "glycan_involvement": "Glycosylation may affect antioxidant activity.", "mechanism": "Low methylation and altered expression in various cancers.", "protein": "PRDX1", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by ", "gene_name": "PRDX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q06830" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "low", "disease": "Pan-cancer", "glycan_involvement": "Glycosylation may affect cytoskeletal interactions.", "mechanism": "Low methylation and altered expression in various cancers.", "protein": "PDLIM1", "protein_enriched": { "function": "May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both sk", "gene_name": "PDLIM7", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G57321FI", "G70994MS" ], "uniprot_id": "Q9NR12" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201601" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation may modulate drug response and cytoskeletal function.", "mechanism": "ACTN4 correlates with drug sensitivity (Oxaliplatin) and immune infiltration.", "protein": "ACTN4", "protein_enriched": { "function": "F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its assoc", "gene_name": "ACTN4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "O43707" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201601" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "EGFR is a glycoprotein; glycosylation affects ligand binding and receptor activation.", "mechanism": "EGFR overexpression/mutation drives proliferation; targeted by TKIs.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 is glycosylated; glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 expression on tumor cells inhibits T-cell attack; targeted by immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "ALK is a glycoprotein; glycosylation may affect receptor stability and signaling.", "mechanism": "ALK rearrangements drive oncogenesis; targeted by ALK inhibitors.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "ROS1 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "ROS1 fusions drive tumorigenesis; targeted by ROS1 inhibitors.", "protein": "ROS1", "protein_enriched": { "function": "Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous s", "gene_name": "ROS1", "glycan_count": 1, "glycosylation_sites_count": 30, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08922" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-1 is glycosylated; glycosylation may modulate receptor-ligand interaction.", "mechanism": "PD-1 on T cells inhibits immune response; targeted by monoclonal antibodies.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "E-cadherin is glycosylated; glycosylation affects cell adhesion.", "mechanism": "Loss of E-cadherin promotes metastasis and TKI resistance; HDAC inhibitors restore expression.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201636" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "TIM-3 contains mucin domain; O-glycosylation likely modulates function.", "mechanism": "TIM-3 on T cells regulates immune exhaustion; potential target for immunotherapy.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "LAG-3 is glycosylated; glycosylation may affect MHC II binding.", "mechanism": "LAG-3 on T cells inhibits activation; co-expressed with PD-1/TIM-3 in TILs.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "PARP1 is a glycoprotein; glycosylation may affect nuclear localization.", "mechanism": "PARP1 involved in DNA repair; inhibitors induce tumor cell death.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "VEGFR is glycosylated; glycosylation affects ligand binding and receptor activation.", "mechanism": "VEGFR signaling promotes angiogenesis; targeted by anti-VEGF therapies.", "protein": "VEGFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201636" }, { "confidence": "high", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "Fibrinogen is N-glycosylated, affecting its stability and clotting function.", "mechanism": "Elevated fibrinogen levels indicate hypercoagulability and inflammation in COVID-19 patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201770" }, { "confidence": "high", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "D-dimer is derived from glycosylated fibrinogen; glycosylation affects degradation rate.", "mechanism": "High D-dimer levels reflect increased fibrin degradation and are associated with poor prognosis.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11201770" }, { "confidence": "high", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and stability.", "mechanism": "IL-6 upregulates tissue factor and induces hepatic synthesis of fibrinogen, promoting thrombosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "IL-5 glycosylation may affect secretion and immune modulation.", "mechanism": "Higher IL-5 levels are associated with prolonged bleeding time (INR, PT) in COVID-19.", "protein": "Interleukin-5 (IL-5)", "relationship_type": "biomarker", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "IL-17F glycosylation may influence receptor interaction.", "mechanism": "Lower IL-17F predicts higher INR; IL-17F modulates endothelial function and thrombosis.", "protein": "Interleukin-17F (IL-17F)", "protein_enriched": { "function": "Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage ", "gene_name": "DGAT2", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G17208MA", "G23505EP", "G28541PG", "G35541EV", "G46691LC", "G83646BJ" ], "uniprot_id": "Q96PD7" }, "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "IFN-\u03b3 glycosylation affects secretion and activity.", "mechanism": "Lower IFN-\u03b3 levels predict higher aPTT; IFN-\u03b3 modulates antiviral response and coagulation.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "TNF-\u03b1 glycosylation influences receptor binding.", "mechanism": "Elevated TNF-\u03b1 contributes to endothelial activation and coagulation cascade.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "LL-37 is processed from glycosylated precursor; glycosylation may affect activity.", "mechanism": "LL-37 increases activity of coagulation factors (FXa, thrombin), promoting hypercoagulation.", "protein": "Cathelicidin (LL-37)", "protein_enriched": { "function": "Antimicrobial protein that is an integral component of the innate immune system (PubMed:14978112, PubMed:16637646, PubMed:18818205, PubMed:22879591, PubMed:9736536). Binds to bacterial lipopolysacchar", "gene_name": "CAMP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P49913" }, "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "high", "disease": "Thromboembolism", "glycan_involvement": "N-glycosylation of fibrinogen affects clot structure and resistance to fibrinolysis.", "mechanism": "High fibrinogen levels promote clot formation and risk of thromboembolic events in COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "high", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "IL-6 glycosylation modulates inflammatory signaling.", "mechanism": "IL-6-driven inflammation and coagulation contribute to ARDS pathogenesis in severe COVID-19.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11201770" }, { "confidence": "medium", "disease": "Central Precocious Puberty", "glycan_involvement": "SHBG is a glycoprotein; glycosylation may affect its stability and hormone binding capacity.", "mechanism": "SHBG levels are positively correlated with HDL cholesterol; low SHBG is associated with higher body fat and may reflect metabolic status in CPP.", "protein": "Sex Hormone Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11201813" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may modulate SHBG serum half-life and function.", "mechanism": "Low circulating SHBG levels are correlated with increased body fat mass and abdominal fat.", "protein": "Sex Hormone Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11201813" }, { "confidence": "low", "disease": "Metabolic Syndrome", "glycan_involvement": "Altered glycosylation may influence SHBG's metabolic clearance.", "mechanism": "Low SHBG is associated with metabolic syndrome features, including dyslipidemia and insulin resistance.", "protein": "Sex Hormone Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11201813" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation status may affect SHBG's interaction with receptors and hormones.", "mechanism": "Low SHBG is linked to increased risk of type 2 diabetes, possibly via effects on insulin sensitivity.", "protein": "Sex Hormone Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11201813" }, { "confidence": "low", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation may influence SHBG's circulatory levels and function.", "mechanism": "Low SHBG and associated dyslipidemia may increase cardiovascular risk in early puberty.", "protein": "Sex Hormone Binding Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11201813" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "APOA1 is N-glycosylated; glycosylation affects stability and lipid binding.", "mechanism": "Downregulation under microgravity impairs lipid transport, promoting hepatic lipid accumulation.", "protein": "APOA1", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "APOA2 is N-glycosylated; glycosylation modulates secretion and function.", "mechanism": "Downregulation reduces lipid export, contributing to steatosis.", "protein": "APOA2", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "APOB is heavily N-glycosylated; glycosylation is critical for VLDL assembly.", "mechanism": "Downregulation impairs VLDL secretion, leading to hepatic lipid accumulation.", "protein": "APOB", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "PTDSS1 is a glycoprotein; glycosylation may regulate localization/activity.", "mechanism": "Upregulation alters glycerophospholipid metabolism, affecting membrane composition.", "protein": "PTDSS1", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation modulates HMGCR stability and ER localization.", "mechanism": "Altered expression affects cholesterol biosynthesis.", "protein": "HMGCR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Ketone body deficiency", "glycan_involvement": "N-glycosylation may affect mitochondrial import and function.", "mechanism": "Downregulation reduces ketogenesis, leading to energy deficits.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "CPT2 is glycosylated; glycosylation may affect mitochondrial targeting.", "mechanism": "Downregulation impairs fatty acid \u03b2-oxidation, promoting lipid accumulation.", "protein": "CPT2", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "ACOT2 is a glycoprotein; glycosylation may regulate activity.", "mechanism": "Downregulation decreases fatty acid oxidation, contributing to steatosis.", "protein": "ACOT2", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "medium", "disease": "Ketone body deficiency", "glycan_involvement": "HMGCL is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "Downregulation impairs ketone body production.", "protein": "HMGCL", "relationship_type": "causal", "source_pmcid": "PMC11201887" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation essential for APOB secretion and function.", "mechanism": "Altered APOB levels reflect impaired lipoprotein metabolism.", "protein": "APOB", "relationship_type": "biomarker", "source_pmcid": "PMC11201887" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Gn is part of the viral envelope, mediates host cell entry and immune evasion.", "protein": "Gn glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation affects receptor binding and fusion activity.", "mechanism": "Gc binds LDLR on host cells, facilitating viral attachment and entry.", "protein": "Gc glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Contains N-terminal domain with Furin-cleaved mucin-like region.", "mechanism": "Targeted by non-neutralizing antibodies that confer protection in animal models.", "protein": "GP38", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201903" }, { "confidence": "medium", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Mucin-like domain is highly glycosylated, may affect immune recognition.", "mechanism": "Secreted glycoprotein, role in immune modulation and viral maturation.", "protein": "GP85/GP160 (MLD-GP38)", "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "medium", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Likely glycosylated, impacts trafficking and function.", "mechanism": "Double-membrane-spanning protein, involved in viral assembly and egress.", "protein": "NSm", "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Not a glycoprotein, but interacts with glycoproteins during assembly.", "mechanism": "Highly conserved, used as antigen in ELISA for early diagnosis.", "protein": "Nucleoprotein (NP)", "relationship_type": "biomarker", "source_pmcid": "PMC11201903" }, { "confidence": "high", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "LDLR is N-glycosylated, glycosylation required for proper folding and surface expression.", "mechanism": "Host receptor for CCHFV Gc, essential for viral entry and pathogenesis.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "medium", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation affects lipid binding and immune modulation.", "mechanism": "Associated with CCHFV particles, may modulate infection and immune response.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11201903" }, { "confidence": "medium", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation status may affect chaperone activity.", "mechanism": "Interacts with NP, may assist in viral replication and host stress response.", "protein": "Heat shock protein 70 (HSP70)", "relationship_type": "protective", "source_pmcid": "PMC11201903" }, { "confidence": "low", "disease": "Crimean-Congo Hemorrhagic Fever (CCHF)", "glycan_involvement": "Glycosylation impacts membrane localization and function.", "mechanism": "Upregulated in response to infection, may confer cellular protection.", "protein": "Aquaporin 6", "relationship_type": "protective", "source_pmcid": "PMC11201903" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation critical for receptor folding and cell surface expression.", "mechanism": "GLP-1 receptor agonists stimulate insulin secretion, reduce blood glucose, and promote weight loss.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects receptor function and ligand binding.", "mechanism": "GLP-1 receptor agonists reduce appetite and increase satiety, leading to weight loss.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates receptor signaling and stability.", "mechanism": "GLP-1 receptor activation exerts anti-atherogenic and anti-inflammatory effects, reducing cardiovascular risk.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "protective", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation required for proper receptor function.", "mechanism": "GIP receptor agonists improve beta-cell function and insulin secretion, especially when combined with GLP-1 agonists.", "protein": "GIP receptor", "protein_enriched": { "function": "Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis a", "gene_name": "Tpi1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48500" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201978" }, { "confidence": "medium", "disease": "Metabolic-associated fatty liver disease (MAFLD)", "glycan_involvement": "N-glycosylation influences receptor trafficking and signaling.", "mechanism": "Glucagon receptor activation reduces hepatic triglyceride content and improves liver metabolism.", "protein": "Glucagon receptor", "protein_enriched": { "function": "G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glyco", "gene_name": "GCGR", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P47871" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "O-glycosylation and multimerization essential for bioactivity.", "mechanism": "Adiponectin secretion is reduced in obesity; higher levels are anti-inflammatory and improve insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "TNF\u03b1 produced in adipose tissue promotes inflammation and insulin resistance.", "protein": "TNF\u03b1", "relationship_type": "causal", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation required for secretion and receptor interaction.", "mechanism": "Leptin levels increase in obesity but leptin resistance develops, limiting therapeutic use.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11201978" }, { "confidence": "medium", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "N-glycosylation modulates receptor activity in cardiac tissue.", "mechanism": "GLP-1 receptor agonists improve cardiac function and reduce symptoms in obese patients with HFpEF.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11201978" }, { "confidence": "low", "disease": "Pancreatitis", "glycan_involvement": "No direct evidence for glycan involvement in risk.", "mechanism": "GLP-1 receptor agonists may rarely increase risk of pancreatitis.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "risk", "source_pmcid": "PMC11201978" }, { "confidence": "high", "disease": "Pancreatic Ductal Adenocarcinoma (PDAC)", "glycan_involvement": "CA 19-9 is a sialylated Lewis antigen (glycan epitope) expressed on mucin-type glycoproteins; its detection relies on glycosylation status.", "mechanism": "CA 19-9 is elevated in the blood of patients with PDAC and is used for diagnosis, monitoring response to therapy, and selection for surgery.", "protein": "Carbohydrate Antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11202096" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Heavily O-glycosylated mucin domains mediate EV binding and function.", "mechanism": "PRG-4 is significantly upregulated in EVs from ALS patients; levels correlate with cognitive status.", "protein": "Proteoglycan 4 (PRG-4)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "high", "disease": "Cognitive impairment in ALS", "glycan_involvement": "O-glycosylation enables PRG-4 interaction with EVs and possibly neuroprotective effects.", "mechanism": "Higher PRG-4 levels in EVs are associated with normal cognitive function; decreased in ALS patients with cognitive impairment.", "protein": "Proteoglycan 4 (PRG-4)", "relationship_type": "protective", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Glycosylation critical for anti-inflammatory and barrier-protective functions.", "mechanism": "Exogenous PRG-4 reduces neuroinflammation and restores blood-brain barrier after injury.", "protein": "Proteoglycan 4 (PRG-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation affects fibrinogen function and cell interactions.", "mechanism": "FIBA is upregulated in EVs from ALS patients; associated with inflammation and tissue healing.", "protein": "Fibrinogen alpha chain (FIBA)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation modulates fibrinogen stability and activity.", "mechanism": "FIBB upregulation in EVs correlates with longer survival in ALS patients.", "protein": "Fibrinogen beta chain (FIBB)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation influences fibrinogen\u2019s role in inflammation.", "mechanism": "FIBG is upregulated in EVs from ALS patients; involved in neuroinflammatory processes.", "protein": "Fibrinogen gamma chain (FIBG)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Extensive N- and O-glycosylation regulates VWF multimerization and function.", "mechanism": "VWF upregulated in EVs; linked to complement/coagulation cascades and ALS progression.", "protein": "Von Willebrand factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation required for complement activation and MAC formation.", "mechanism": "C9 upregulated in EVs; higher levels associated with lower ALSFRS-R scores (worse function).", "protein": "Complement component 9 (C9)", "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation modulates LBP\u2019s immune response functions.", "mechanism": "LBP increased in EVs and CSF of ALS patients; correlates with ALSFRS-R score.", "protein": "Lipopolysaccharide-binding protein (LBP)", "protein_enriched": { "function": "Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:2412035", "gene_name": "LBP", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G84452RH", "G94470IW" ], "uniprot_id": "P18428" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202157" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "O-glycosylation essential for anti-inflammatory activity.", "mechanism": "PRG-4 reduces neuroinflammation by restoring barrier integrity.", "protein": "Proteoglycan 4 (PRG-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202157" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "\u03b1-syn is a glycoprotein; glycosylation may affect aggregation and toxicity.", "mechanism": "Misfolding and aggregation into Lewy bodies; epigenetic dysregulation increases \u03b1-syn expression.", "protein": "Alpha-synuclein (\u03b1-syn)", "relationship_type": "causal", "source_pmcid": "PMC11202179" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MOG is a glycoprotein; glycosylation is critical for myelin structure and immune recognition.", "mechanism": "Aberrant methylation of MOG gene in MS patients; impacts myelin integrity.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC11202179" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "CD47 is a glycoprotein; glycosylation modulates its 'don't eat me' signal.", "mechanism": "Downregulation by miRNAs leads to increased phagocytosis of myelin by macrophages.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "causal", "source_pmcid": "PMC11202179" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "MBP is glycosylated; glycan modifications may affect susceptibility to citrullination.", "mechanism": "PAD2-mediated citrullination of MBP disrupts myelin integrity.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "causal", "source_pmcid": "PMC11202179" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "GBA is a glycoprotein; glycosylation affects enzyme stability and trafficking.", "mechanism": "Mutations in GBA gene increase risk of PD; affects lysosomal function and \u03b1-syn clearance.", "protein": "Glucocerebrosidase (GBA)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11202179" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "DAT is glycosylated; glycosylation affects transporter function.", "mechanism": "Hypermethylation of DAT gene in PD; reduces dopamine reuptake.", "protein": "Dopamine Transporter (DAT)", "relationship_type": "biomarker", "source_pmcid": "PMC11202179" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "ICAM5 is a glycoprotein; glycosylation influences immune interactions.", "mechanism": "Hypermethylation reduces ICAM5 expression; impacts anti-inflammatory cytokine secretion.", "protein": "ICAM5", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2)", "gene_name": "ICAM5", "glycan_count": 5, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G81315DD", "G80920RR", "G83460ZZ", "G22573RC" ], "uniprot_id": "Q9UMF0" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11202179" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "PGC1\u03b1 is glycosylated; glycosylation may affect transcriptional activity.", "mechanism": "\u03b1-syn binding reduces PGC1\u03b1 expression via histone hypoacetylation; leads to mitochondrial dysfunction.", "protein": "PGC1\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202179" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "SOD1 is glycosylated; glycosylation may affect aggregation propensity.", "mechanism": "Mutant SOD1 aggregates in motor neurons; altered DNA/histone methylation affects expression.", "protein": "SOD1", "relationship_type": "causal", "source_pmcid": "PMC11202179" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "PAD2 is glycosylated; glycosylation may regulate enzyme activity.", "mechanism": "Hypomethylation/upregulation of PAD2 increases citrullination of MBP and histones, promoting demyelination.", "protein": "PAD2", "protein_enriched": { "function": "Catalyzes the deimination of arginine residues of proteins", "gene_name": "PADI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2J8" }, "relationship_type": "causal", "source_pmcid": "PMC11202179" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and ligand binding.", "mechanism": "PD-1 is targeted by nivolumab to block immune checkpoint inhibition, enhancing anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-L1 is heavily glycosylated; glycosylation modulates its cell surface expression and immune evasion.", "mechanism": "PD-L1 expression in tumors is associated with increased risk of recurrence and shortened survival.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of PD-L1 is required for its stability and function.", "mechanism": "PD-L1 is targeted by immune checkpoint inhibitors to restore anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "Glycosylation may affect PD-1 antibody binding and therapeutic efficacy.", "mechanism": "Nivolumab blocks PD-1, improving survival in uHCC patients after sorafenib failure.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202187" }, { "confidence": "medium", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "Glycosylation status may influence PD-L1 detection and therapeutic response.", "mechanism": "Positive PD-L1 expression is associated with better response rates to PD-1/PD-L1 inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum detectability.", "mechanism": "AFP levels are used to assess disease status and progression in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202187" }, { "confidence": "medium", "disease": "Compensated cirrhosis", "glycan_involvement": "Glycosylation may modulate PD-1 function in immune regulation.", "mechanism": "Early uptake of PD-1 inhibitors (nivolumab) in compensated cirrhosis with HCC improves survival.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202187" }, { "confidence": "medium", "disease": "Compensated cirrhosis", "glycan_involvement": "Glycosylation affects PD-L1 stability and immune interactions.", "mechanism": "PD-L1 expression may be relevant for predicting response to immunotherapy in cirrhotic HCC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation is essential for PD-1/PD-L1 functional interactions.", "mechanism": "PD-1/PD-L1 pathway contributes to immune evasion and tumor progression in HCC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect antibody recognition and therapeutic efficacy.", "mechanism": "Blocking PD-L1 with antibodies can restore anti-tumor immunity and prolong survival.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "protective", "source_pmcid": "PMC11202187" }, { "confidence": "high", "disease": "Liver Fibrosis/Cirrhosis", "glycan_involvement": "Binds mannose-rich glycans on pathogens and endogenous ligands.", "mechanism": "Expressed on Kupffer cells, mediates pathogen recognition and clearance, modulates inflammation.", "protein": "Mannose Receptor (MR)", "relationship_type": "biomarker", "source_pmcid": "PMC11202214" }, { "confidence": "high", "disease": "NAFLD/NASH", "glycan_involvement": "TLRs are glycoproteins; glycosylation affects ligand recognition and signaling.", "mechanism": "TLR activation on macrophages promotes M1 polarization and inflammation, driving liver injury.", "protein": "Toll-like Receptors (TLRs)", "relationship_type": "causal", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "PD-L1 is N-glycosylated; glycosylation modulates immune checkpoint function.", "mechanism": "Macrophage autophagy suppresses PD-L1 expression, hindering HCC progression.", "protein": "Programmed Cell Death Ligand 1 (PD-L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "NAFLD/NASH", "glycan_involvement": "AIM is a plasma glycoprotein; glycosylation may affect stability and function.", "mechanism": "AIM produced by macrophages regulates apoptosis and inflammation in fatty liver disease.", "protein": "Alpha-1-microglobulin (AIM)", "relationship_type": "biomarker", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "Liver Fibrosis/Cirrhosis", "glycan_involvement": "TIM-4 is a mucin-domain glycoprotein; O-glycosylation may regulate ligand binding.", "mechanism": "TIM-4 on macrophages inhibits ROS and TGF-\u03b21, reducing fibrosis.", "protein": "TIM-4", "protein_enriched": { "function": "Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation. Controls T-cell activation in a bimodal fashion, decreasing th", "gene_name": "TIMD4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q96H15" }, "relationship_type": "protective", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "NAFLD/NASH", "glycan_involvement": "CD36 is N-glycosylated; glycosylation affects lipid binding and receptor function.", "mechanism": "CD36-mediated lipid uptake in M2 macrophages increases susceptibility to ferroptosis, promoting inflammation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Siglec-14 binds sialylated glycans; glycosylation critical for ligand recognition.", "mechanism": "Siglec-14 activation in macrophages triggers NLRP3 inflammasome and pyroptosis during bacterial infection.", "protein": "Siglec-14", "protein_enriched": { "function": "Binds sialylated glycoproteins", "gene_name": "SIGLEC15", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q6ZMC9" }, "relationship_type": "causal", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "ALI", "glycan_involvement": "NLRP3 is a glycoprotein; glycosylation may affect inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation in macrophages drives pyroptosis and liver inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC11202214" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "SRs are glycoproteins; glycosylation modulates ligand binding.", "mechanism": "SRs on macrophages mediate uptake of modified lipoproteins, contributing to foam cell formation and vascular inflammation.", "protein": "Scavenger Receptors (SR)", "relationship_type": "causal", "source_pmcid": "PMC11202214" }, { "confidence": "low", "disease": "Autoimmune Hepatitis", "glycan_involvement": "CRs are glycoproteins; glycosylation affects complement binding.", "mechanism": "CRs on Kupffer cells mediate immune complex clearance, modulating autoimmune liver injury.", "protein": "Complement Receptors (CRs)", "relationship_type": "biomarker", "source_pmcid": "PMC11202214" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency (AATD)", "glycan_involvement": "AAT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Mutations in SERPINA1 gene lead to deficient or dysfunctional AAT protein.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal", "source_pmcid": "PMC11202262" }, { "confidence": "high", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Glycosylation status influences AAT folding and ER retention.", "mechanism": "Misfolded AAT accumulates in hepatocytes, causing cellular damage and liver disease.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Neonatal icterus prolongatus/cholestasis", "glycan_involvement": "Not directly discussed, but AAT glycosylation may affect secretion and clearance.", "mechanism": "Early manifestation of liver involvement in AATD; associated with severe disease course.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Atopic diseases (allergic rhino-conjunctivitis, atopic dermatitis, allergic asthma)", "glycan_involvement": "Glycosylation may modulate AAT's inhibitory function on serine proteases.", "mechanism": "AAT deficiency may increase serine protease activity, enhancing histamine release and atopic responses.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal/association", "source_pmcid": "PMC11202262" }, { "confidence": "high", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Glycosylation affects AAT serum half-life and detection.", "mechanism": "Low serum AAT levels indicate risk for liver disease in children.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Not directly discussed.", "mechanism": "Ursodeoxycholic acid (UDCA) used to treat liver disease in AATD patients.", "protein": "Alpha-1-antitrypsin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Not directly discussed.", "mechanism": "Persistent elevation of ALT/GGT in early life may indicate severe liver involvement.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11202262" }, { "confidence": "high", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Mutant AAT glycoprotein is prone to misfolding and aggregation.", "mechanism": "Pi*ZZ genotype (homozygous Glu342Lys) is associated with severe liver disease and need for transplantation.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Liver disease (including cholestasis, cirrhosis, liver failure)", "glycan_involvement": "Proper N-glycosylation is required for AAT secretion.", "mechanism": "Normal glycosylation and secretion of AAT protect against liver disease.", "protein": "Alpha-1-antitrypsin", "relationship_type": "protective", "source_pmcid": "PMC11202262" }, { "confidence": "medium", "disease": "Atopic diseases (allergic rhino-conjunctivitis, atopic dermatitis, allergic asthma)", "glycan_involvement": "Not directly discussed.", "mechanism": "Increased prevalence of atopic disease in AATD patients compared to general population.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11202262" }, { "confidence": "high", "disease": "Ovarian reserve depletion", "glycan_involvement": "AMH is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "AMH levels reflect ovarian reserve and drop rapidly during chemotherapy.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "biomarker", "source_pmcid": "PMC11202309" }, { "confidence": "high", "disease": "Primary ovarian failure (POF)", "glycan_involvement": "Glycosylation essential for AMH bioactivity.", "mechanism": "AMH administration protects PMFs from cyclophosphamide-induced loss via PI3K/AKT/FOXO3a pathway modulation.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "protective", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian reserve depletion", "glycan_involvement": "LH is a glycoprotein; glycosylation required for receptor binding.", "mechanism": "LH administration inhibits PMF depletion during cisplatin therapy, maintaining fertility.", "protein": "Luteinizing hormone (LH)", "relationship_type": "protective", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Oocyte mitochondrial dysfunction", "glycan_involvement": "N-glycosylation affects MDR-1 trafficking and function.", "mechanism": "P-glycoprotein protects oocyte mitochondria from nitrogen mustard-induced oxidative stress.", "protein": "MDR-1/P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian dysfunction", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Inhibin B levels are used to assess ovarian reserve before chemotherapy.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian dysfunction", "glycan_involvement": "Glycosylation modulates FSH receptor binding and half-life.", "mechanism": "FSH levels are measured to evaluate ovarian reserve and function.", "protein": "Follicle-stimulating hormone (FSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian follicle apoptosis", "glycan_involvement": "GDF9 is glycosylated for secretion and function.", "mechanism": "Paclitaxel suppresses GDF9 expression, contributing to follicle damage.", "protein": "GDF9", "protein_enriched": { "function": "Required for ovarian folliculogenesis. Promotes primordial follicle development. Stimulates granulosa cell proliferation. Promotes cell transition from G0/G1 to S and G2/M phases, through an increase ", "gene_name": "GDF9", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O60383" }, "relationship_type": "causal", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian follicle apoptosis", "glycan_involvement": "BMP15 glycosylation required for activity.", "mechanism": "Paclitaxel suppresses BMP15 expression, leading to follicle loss.", "protein": "BMP15", "protein_enriched": { "function": "Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expre", "gene_name": "BMP10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O95393" }, "relationship_type": "causal", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian dysfunction", "glycan_involvement": "Granulosa cell glycoproteins involved in cell survival and signaling.", "mechanism": "Cyclophosphamide induces apoptosis in human granulosa cells via oxidative stress and glutathione deficiency.", "protein": "COV434 granulosa cell proteins", "relationship_type": "causal", "source_pmcid": "PMC11202309" }, { "confidence": "medium", "disease": "Ovarian follicle apoptosis", "glycan_involvement": "Glycosylation not specified for cytochrome c in this context.", "mechanism": "Cyclophosphamide and docetaxel induce cytochrome c release, activating caspases and apoptosis.", "protein": "Cytochrome c", "protein_enriched": { "function": "Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers ", "gene_name": "CYCS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P99999" }, "relationship_type": "causal", "source_pmcid": "PMC11202309" }, { "confidence": "high", "disease": "Ovarian dysfunction", "glycan_involvement": "Glycosylation affects membrane localization and function.", "mechanism": "Regulates follicular angiogenesis and ovulation, impacting egg production.", "protein": "Annexin A2 (ANXA2)", "relationship_type": "biomarker", "source_pmcid": "PMC11202424" }, { "confidence": "medium", "disease": "Impaired Wnt signaling", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Mediates Wnt signaling, affecting follicle development and egg production.", "protein": "Frizzled family receptor 7 (FZD7)", "protein_enriched": { "function": "Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. T", "gene_name": "FZD8", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9H461" }, "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "medium", "disease": "Cell division dysregulation", "glycan_involvement": "Glycosylation may affect protein stability and cell cycle control.", "mechanism": "Regulates cell cycle progression in follicular cells, influencing egg production.", "protein": "Cyclin D1 (CCND1)", "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "medium", "disease": "Low egg production", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Modulates cellular signaling relevant to reproductive physiology.", "protein": "A2B adenosine receptor (ADORA2B)", "protein_enriched": { "function": "Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase", "gene_name": "ADORA2B", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P29275" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202424" }, { "confidence": "medium", "disease": "Impaired glycoprotein metabolism", "glycan_involvement": "Directly involved in O-mannosyl glycan biosynthesis.", "mechanism": "Catalyzes glycan structure formation, affecting matrix integrity and egg production.", "protein": "\u03b2-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2)", "protein_enriched": { "function": "Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis ", "gene_name": "NUDT10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NFP7" }, "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "medium", "disease": "Basement membrane disruption", "glycan_involvement": "Glycosylation regulates enzyme activity and secretion.", "mechanism": "Degrades heparan sulfate, releasing angiogenic mediators and affecting follicle environment.", "protein": "Heparanase (HPSE)", "protein_enriched": { "function": "Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell ", "gene_name": "PLXNA1", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G27058EU", "G40926MX", "G41071NU", "G31852PQ", "G80920RR", "G62765YT", "G57321FI", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9UIW2" }, "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "low", "disease": "Impaired cellular transport", "glycan_involvement": "Glycosylation may affect vesicle formation.", "mechanism": "Regulates vesicle trafficking, impacting protein transport and egg production.", "protein": "SEC31A", "protein_enriched": { "function": "Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER) (PubMed:10788476). The coat has two main functions, the physical", "gene_name": "SEC31A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "O94979" }, "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "low", "disease": "Impaired cellular transport", "glycan_involvement": "Potential glycosylation affects transport efficiency.", "mechanism": "Facilitates nuclear import/export, influencing gene expression in reproductive cells.", "protein": "Importin 13 (IPO13)", "relationship_type": "causal", "source_pmcid": "PMC11202424" }, { "confidence": "low", "disease": "Impaired antioxidant defense", "glycan_involvement": "Glycosylation may modulate enzymatic activity.", "mechanism": "Provides antioxidant protection in ovarian tissue.", "protein": "Peroxiredoxin 6 (PRDX6)", "relationship_type": "protective", "source_pmcid": "PMC11202424" }, { "confidence": "low", "disease": "Impaired glycoprotein metabolism", "glycan_involvement": "SUMOylation interacts with glycosylation pathways.", "mechanism": "Modifies protein signaling and solubility, balancing protein homeostasis.", "protein": "Small ubiquitin-like modifier 1 (SUMO1)", "protein_enriched": { "function": "Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by th", "gene_name": "SUMO1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P63165" }, "relationship_type": "regulatory", "source_pmcid": "PMC11202424" }, { "confidence": "high", "disease": "Embryonic lethality", "glycan_involvement": "BMP2 is secreted as a glycosylated dimer, glycosylation required for function.", "mechanism": "BMP2 deficiency leads to severe cardiac defects and embryonic death.", "protein": "BMP2", "protein_enriched": { "function": "Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Ini", "gene_name": "Bmp2", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07036HW", "G80920RR", "G83633GK" ], "uniprot_id": "P21274" }, "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "medium", "disease": "DiGeorge Syndrome", "glycan_involvement": "CHRD is a secreted glycoprotein; glycosylation affects stability and function.", "mechanism": "Homozygous knockout of CHRD causes early lethality and surviving mice show heart abnormalities.", "protein": "CHRD (Chordin)", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Cardiomyocyte proliferation defects", "glycan_involvement": "BMP10 is glycosylated, required for secretion and activity.", "mechanism": "Notch signaling regulates BMP10 expression; disruption reduces cardiomyocyte proliferation.", "protein": "BMP10", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Notch1 is a glycosylated transmembrane receptor; glycosylation modulates ligand binding.", "mechanism": "Notch1/Hes1 pathway modulated by Cox inhibitors protects against myocardial hypertrophy.", "protein": "Notch1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Cardiac outflow tract defects", "glycan_involvement": "Shh is a glycoprotein; glycosylation required for secretion and activity.", "mechanism": "Shh depletion causes defects in cardiac outflow tract separation.", "protein": "Sonic Hedgehog (Shh)", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Mesoderm formation defects", "glycan_involvement": "FGF2 glycosylation affects stability and receptor binding.", "mechanism": "FGF2 required for mesoderm induction; inhibition reduces mesoderm and cardiac progenitors.", "protein": "FGF2", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "medium", "disease": "Cardiomyocyte proliferation defects", "glycan_involvement": "FGF10 glycosylation required for secretion and receptor interaction.", "mechanism": "FGF10-FGFR interaction promotes cardiomyocyte differentiation; loss impairs proliferation.", "protein": "FGF10", "protein_enriched": { "function": "Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing", "gene_name": "FGF10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O15520" }, "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Mesoderm formation defects", "glycan_involvement": "Wnt3a is a glycoprotein; glycosylation required for secretion and activity.", "mechanism": "Wnt3a knockout impairs mesoderm formation and cardiac differentiation.", "protein": "Wnt3a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/L", "gene_name": "WNT3A", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G85146YR", "G32577BC" ], "uniprot_id": "P56704" }, "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "medium", "disease": "Cardiomyocyte differentiation defects", "glycan_involvement": "FZD is glycosylated; glycosylation affects receptor localization and ligand binding.", "mechanism": "FZD receptor required for Wnt signaling in cardiac mesoderm and cardiomyocyte differentiation.", "protein": "Frizzled (FZD)", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Embryonic lethality", "glycan_involvement": "Jagged1 is a glycosylated ligand; glycosylation modulates Notch activation.", "mechanism": "Jagged1 knockout leads to cardiovascular defects and embryonic death.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC11202427" }, { "confidence": "high", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "ADM is a secreted glycoprotein; glycosylation may affect stability and receptor interaction.", "mechanism": "ADM maintains endothelial cell homeostasis, reduces inflammation, and supports alveolarization; deficiency increases BPD severity.", "protein": "Adrenomedullin (ADM)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11202456" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "Slit2 is a secreted glycoprotein; glycosylation may regulate secretion and function.", "mechanism": "Slit2 downregulation may promote inflammatory cell recruitment and injury; its deficiency could contribute to BPD.", "protein": "Slit2", "relationship_type": "potential protective/causal", "source_pmcid": "PMC11202456" }, { "confidence": "high", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "Mmp9 is glycosylated; glycosylation affects secretion and enzymatic activity.", "mechanism": "Mmp9 upregulation is associated with lung injury and matrix remodeling in BPD.", "protein": "Mmp9", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11202456" }, { "confidence": "high", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "Fgf10 is a glycoprotein; glycosylation may influence receptor binding.", "mechanism": "Fgf10 supports lung development and repair; downregulation is linked to BPD pathogenesis.", "protein": "Fgf10", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11202456" }, { "confidence": "high", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "ICAM1 is heavily N-glycosylated; glycosylation modulates cell adhesion.", "mechanism": "ICAM1 upregulation promotes leukocyte adhesion and inflammation in BPD.", "protein": "ICAM1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11202456" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "STAT3 is O-GlcNAc modified; glycosylation may regulate transcriptional activity.", "mechanism": "STAT3 activation drives inflammatory gene expression in BPD.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC11202456" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "STAT1 is O-GlcNAc modified; glycosylation may affect nuclear localization.", "mechanism": "STAT1 upregulation is linked to increased inflammation in BPD.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "causal", "source_pmcid": "PMC11202456" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "TNFRSF9 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "Upregulated in NK cells in BPD, reflecting increased NK cell activity.", "protein": "TNFRSF9", "protein_enriched": { "function": "Receptor for TNFSF9/4-1BBL. Conveys a signal that enhances CD8(+) T-cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors (Probable)", "gene_name": "TNFRSF9", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G32156ZV", "G27058EU" ], "uniprot_id": "Q07011" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202456" }, { "confidence": "low", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "S100A16 is a glycoprotein; glycosylation may affect secretion.", "mechanism": "Downregulated in endothelial cells in BPD, indicating endothelial dysfunction.", "protein": "S100A16", "protein_enriched": { "function": "Calcium-binding protein. Binds one calcium ion per monomer (PubMed:17030513). Can promote differentiation of adipocytes (in vitro) (By similarity). Overexpression in preadipocytes increases their prol", "gene_name": "S100A16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96FQ6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202456" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia (BPD)", "glycan_involvement": "SIDT1 is a glycoprotein; glycosylation may affect membrane localization.", "mechanism": "SIDT1 is an NK cell marker upregulated in BPD, reflecting increased NK cell infiltration.", "protein": "SIDT1", "protein_enriched": { "function": "Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into a", "gene_name": "HPS4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NQG7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202456" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Derived from glycosylated CD14; glycosylation affects stability and recognition.", "mechanism": "Elevated plasma levels reflect monocyte/macrophage activation in response to bacterial infection.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "high", "disease": "Septic Shock", "glycan_involvement": "Originates from glycosylated CD14; glycan structure may influence cleavage and release.", "mechanism": "Higher levels correlate with severity and mortality risk in septic shock.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Glycosylation of CD14 impacts immune recognition.", "mechanism": "Distinguishes between septic and non-septic SIRS; elevated in sepsis.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Fungemia", "glycan_involvement": "Glycosylation of CD14 may affect interaction with fungal components.", "mechanism": "Elevated levels in fungal bloodstream infections; correlates with disease severity.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of CD14 may modulate immune response to viral infection.", "mechanism": "Levels increase with disease severity and predict mortality; reflects monocyte activation.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation of CD14 influences immune activation.", "mechanism": "Elevated in ARDS, especially sepsis-related ARDS; predicts mortality.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Ventilator-Associated Pneumonia (VAP)", "glycan_involvement": "Glycosylation of CD14 may affect pathogen recognition.", "mechanism": "Higher levels in VAP and sepsis; correlates with disease severity.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Multiorgan Dysfunction", "glycan_involvement": "Glycosylation of CD14 impacts systemic inflammatory signaling.", "mechanism": "Levels correlate with number and severity of organ failures in sepsis.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "medium", "disease": "Acute Renal Failure", "glycan_involvement": "Glycosylation may affect renal clearance.", "mechanism": "Levels are elevated due to reduced excretion; interpretation requires adjustment for renal function.", "protein": "Presepsin (sCD14-ST)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202475" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation critical for membrane localization and LPS binding.", "mechanism": "Acts as LPS receptor, initiating inflammatory cascade leading to sepsis.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC11202475" }, { "confidence": "high", "disease": "Malnutrition\u2013Inflammation Syndrome (MICS)", "glycan_involvement": "AGP is heavily N-glycosylated; glycan changes modulate its acute-phase response.", "mechanism": "AGP levels rise during inflammation, reflecting the malnutrition\u2013inflammation state in hemodialysis patients.", "protein": "Alpha-1-Acid Glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Acute Events (general)", "glycan_involvement": "CRP is glycosylated; glycan structure affects its inflammatory activity.", "mechanism": "Elevated CRP predicts risk of acute events (sepsis, MI, stroke) in hemodialysis patients.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Protein-Energy Wasting (PEW)", "glycan_involvement": "Albumin is glycosylated; glycan status may affect stability and half-life.", "mechanism": "Low serum albumin indicates poor nutritional status and predicts PEW.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "medium", "disease": "Malnutrition\u2013Inflammation Syndrome (MICS)", "glycan_involvement": "TTR is glycosylated; glycan modifications may influence its transport function.", "mechanism": "Low TTR reflects impaired hepatic protein synthesis and malnutrition.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "AGP glycosylation changes during sepsis, affecting immunomodulatory properties.", "mechanism": "AGP levels increase during sepsis, indicating systemic inflammation.", "protein": "Alpha-1-Acid Glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "CRP glycosylation modulates its binding to ligands and inflammatory activity.", "mechanism": "High CRP is associated with increased risk of MI in hemodialysis patients.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "AGP glycan changes influence vascular inflammation.", "mechanism": "Elevated AGP correlates with increased risk of stroke in inflammatory states.", "protein": "Alpha-1-Acid Glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Mortality in Hemodialysis Patients", "glycan_involvement": "Albumin glycosylation may affect its clearance and function.", "mechanism": "Low albumin is a strong predictor of mortality in hemodialysis patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "AGP glycan structures modulate endothelial interactions.", "mechanism": "AGP is associated with vascular inflammation and atherosclerosis risk.", "protein": "Alpha-1-Acid Glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "AGP glycosylation patterns change in diabetes, affecting its function.", "mechanism": "AGP is elevated in diabetic nephropathy, reflecting chronic inflammation.", "protein": "Alpha-1-Acid Glycoprotein (AGP)", "relationship_type": "biomarker", "source_pmcid": "PMC11202559" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed; ANG is a secreted glycoprotein.", "mechanism": "Loss-of-function (LoF) mutations in ANG gene impair neuroprotective and angiogenic activity, leading to motoneuron degeneration.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Wild-type ANG promotes motoneuron survival and protects against hypoxia-induced neuronal death.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "protective", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Some ANG mutants (e.g., S28N, K40I, R31K, P112L, C39W, I46V, H114R, R121H/C) reduce ribonucleolytic activity or nuclear translocation, leading to ALS.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Excessive ANG activity (e.g., R121H/C mutants) may switch from protective to detrimental, accelerating ALS progression.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Not directly discussed.", "mechanism": "Some ANG mutations are associated with PD onset, likely via loss of neuroprotective function.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed; RNase 4 is a secreted glycoprotein.", "mechanism": "RNase 4 LoF mutations (e.g., T(-13)S, R10W, E48D, V75I, A98V, D2E, N26K, T79A, G119S, M29I, R31T, R32W, H72P, R95W) are associated with ALS onset.", "protein": "RNase 4", "protein_enriched": { "function": "Cleaves preferentially after uridine bases (PubMed:3467790). Has antimicrobial activity against uropathogenic E.coli (UPEC) (PubMed:33818125). Probably contributes to urinary tract sterility (PubMed:3", "gene_name": "RNASE4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P34096" }, "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not discussed.", "mechanism": "Mutant SOD1 forms toxic aggregates, causing motoneuron degeneration in ALS.", "protein": "SOD1", "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not discussed.", "mechanism": "TDP-43 mutations and aggregation are central to ALS pathogenesis.", "protein": "TDP-43", "relationship_type": "causal", "source_pmcid": "PMC11202570" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Not directly discussed.", "mechanism": "ANG promotes tumor growth via angiogenesis.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11202570" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Not directly discussed.", "mechanism": "Elevated serum ANG levels observed in ALS patients, possibly as a compensatory response.", "protein": "Angiogenin (RNase 5)", "protein_enriched": { "function": "Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context (PubMed:12051708, PubMed:1400510, PubMed:19332886, PubMed:20129916, PubMed:218558", "gene_name": "ANG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03950" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202570" }, { "confidence": "high", "disease": "Hutchinson-Gilford Progeria Syndrome (HGPS)", "glycan_involvement": "Altered O-glycosylation implicated in progeria; progerin itself may affect glycoprotein processing.", "mechanism": "Progerin accumulation disrupts nuclear lamina, alters chromatin organization and histone modifications (notably H3K27me3), leading to premature aging.", "protein": "Progerin (mutant Lamin A)", "relationship_type": "causal", "source_pmcid": "PMC11202709" }, { "confidence": "high", "disease": "Mandibuloacral Dysplasia (MAD)", "glycan_involvement": "Glycosylation status may affect lamin A/C function and nuclear envelope integrity.", "mechanism": "LMNA mutations disrupt nuclear lamina and chromatin anchorage, causing premature aging phenotypes.", "protein": "Lamin A/C", "relationship_type": "causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Restrictive Dermopathy (RD)", "glycan_involvement": "ZMPSTE24 is a glycoprotein; glycosylation may influence its protease activity.", "mechanism": "ZMPSTE24 mutations impair lamin A processing, leading to nuclear envelope defects and progeroid features.", "protein": "ZMPSTE24", "protein_enriched": { "function": "Transmembrane metalloprotease whose catalytic activity is critical for processing lamin A/LMNA on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum (PubMed:33293", "gene_name": "ZMPSTE24", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O75844" }, "relationship_type": "causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Progeroid Syndromes (general)", "glycan_involvement": "Defective glycosaminoglycan (GAG) chains and O-glycosylation impact ECM and cell signaling.", "mechanism": "Abnormal proteoglycan biosynthesis and metabolism linked to progeroid-like symptoms.", "protein": "Proteoglycans", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Hutchinson-Gilford Progeria Syndrome (HGPS)", "glycan_involvement": "Primary form of protein glycosylation affected in progeria.", "mechanism": "Altered O-glycosylation is implicated in HGPS pathogenesis.", "protein": "O-glycosylated proteins", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11202709" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "EZH2 is a glycoprotein; glycosylation may modulate its stability/activity.", "mechanism": "EZH2-mediated H3K27me3 silences tumor suppressor genes; overexpression/mutation drives oncogenesis.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Potential glycosylation may affect chromatin binding.", "mechanism": "HP1 binds H3K9me3, promoting heterochromatin compaction; dysregulation affects genome stability and cancer risk.", "protein": "HP1 (Heterochromatin Protein 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation may regulate PcG protein interactions.", "mechanism": "PcG proteins mediate H3K27me3, repressing differentiation genes; overactivity linked to tumorigenesis.", "protein": "Polycomb group proteins (PcG)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11202709" }, { "confidence": "high", "disease": "Leukemia", "glycan_involvement": "MLL is a glycoprotein; glycosylation may affect chromatin targeting.", "mechanism": "MLL fusions drive aberrant H3K4 methylation, maintaining leukemia stem cells.", "protein": "MLL fusion proteins", "relationship_type": "causal", "source_pmcid": "PMC11202709" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Altered GAG chains and glycosylation affect tumor microenvironment.", "mechanism": "Proteoglycan metabolism and biosynthesis pathways enriched in cancer and progeroid syndromes.", "protein": "Proteoglycans", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11202709" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "IL-2R\u03b1 is a glycoprotein; glycosylation is required for surface expression and function.", "mechanism": "Tax induces CARM1, which epigenetically activates IL-2R\u03b1 expression, promoting T-cell proliferation and leukemogenesis.", "protein": "IL-2R\u03b1 (Interleukin-2 receptor alpha)", "relationship_type": "causal", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "ICAM-1 glycosylation modulates ligand binding and immune interactions.", "mechanism": "Tax upregulates ICAM-1, facilitating cell adhesion and possibly contributing to leukemic cell interactions.", "protein": "CD54 (ICAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "CD44 glycosylation affects hyaluronan binding and cell migration.", "mechanism": "Tax induces CD44, enhancing cell adhesion and migration, supporting leukemic phenotype.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "OX40L glycosylation is important for receptor binding.", "mechanism": "Tax upregulates OX40L, promoting T-cell activation and survival.", "protein": "Tax-transcriptionally activated glycoprotein 1, 34 kD (TNFSF4/OX40L)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production", "gene_name": "TNFSF4", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P23510" }, "relationship_type": "causal", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "MHC I glycosylation is essential for peptide presentation.", "mechanism": "Tax increases MHC I expression, affecting immune recognition of leukemic cells.", "protein": "Major Histocompatibility Complex, class I (MHC I)", "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "CD70 glycosylation affects ligand-receptor interactions.", "mechanism": "Tax induces CD70, contributing to T-cell activation and proliferation.", "protein": "CD70 (TNFSF7)", "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATL)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Tax induces CARM1, which epigenetically activates growth-promoting genes; CARM1 inhibition suppresses Tax-driven proliferation.", "protein": "CARM1 (PRMT4)", "protein_enriched": { "function": "Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stabili", "gene_name": "CARM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86X55" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202806" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "CARM1 acts as a coactivator for transcription factors (ER\u03b1, \u03b2-catenin, E2F), promoting cancer cell growth.", "protein": "CARM1 (PRMT4)", "protein_enriched": { "function": "Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stabili", "gene_name": "CARM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86X55" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11202806" }, { "confidence": "medium", "disease": "HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Upregulation of IL-2R\u03b1 may contribute to immune activation in neuroinflammatory disease.", "protein": "IL-2R\u03b1 (Interleukin-2 receptor alpha)", "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation modulates CD44 function in metastasis.", "mechanism": "CD44 overexpression is associated with cancer cell migration and metastasis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11202806" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "GPVI is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated soluble GPVI in blood correlates with increased BMI and platelet activation.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "biomarker", "source_pmcid": "PMC11202821" }, { "confidence": "high", "disease": "Lipedema", "glycan_involvement": "PF4 binds glycosaminoglycans (GAGs) in ECM, influencing tissue remodeling.", "mechanism": "PF4 is increased in plasma extracellular vesicles in lipedema and lymphatic disorders.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Lipedema", "glycan_involvement": "TGF-\u03b2 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Upregulated TGF-\u03b2 in platelets promotes hypercoagulability and fibrosis, increasing VTE risk.", "protein": "Transforming Growth Factor Beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Lipedema", "glycan_involvement": "KS is a glycosaminoglycan; its synthesis and modification affect ECM organization.", "mechanism": "Upregulation of KS in platelets may reduce edema by binding sodium and water.", "protein": "Keratan Sulfate (KS)", "relationship_type": "protective", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Lipedema", "glycan_involvement": "SNARE proteins are glycosylated, influencing vesicle fusion and secretion.", "mechanism": "Upregulated SNARE-mediated exocytosis increases platelet granule release, promoting thrombosis.", "protein": "SNARE proteins", "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "NAPB glycosylation may affect its interaction with NSF and exocytosis efficiency.", "mechanism": "Upregulation in Class II obesity enhances NSF-mediated granule exocytosis, increasing thrombosis risk.", "protein": "NAPB", "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "GOLGB1 is a Golgi glycoprotein; glycosylation impacts vesicular trafficking.", "mechanism": "Upregulation in Class II obesity is associated with increased platelet activation and thrombosis.", "protein": "GOLGB1", "protein_enriched": { "function": "May participate in forming intercisternal cross-bridges of the Golgi complex", "gene_name": "GOLGB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14789" }, "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may modulate STARD8 stability and activity.", "mechanism": "Upregulation regulates RhoA, promoting platelet granule secretion and thrombosis.", "protein": "STARD8", "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Lipedema", "glycan_involvement": "Glycosylation may affect mitochondrial targeting and enzyme activity.", "mechanism": "Downregulation impairs mitochondrial fatty acid oxidation, contributing to metabolic derangement.", "protein": "HSD17B10 (17\u03b2-HSD)", "protein_enriched": { "function": "Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulate", "gene_name": "HSD17B2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P37059" }, "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "medium", "disease": "Lipedema", "glycan_involvement": "Glycosylation may regulate BNIP3L membrane localization and function.", "mechanism": "Upregulation promotes mitophagy and apoptosis, potentially increasing platelet activation and VTE risk.", "protein": "BNIP3L", "protein_enriched": { "function": "Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits ", "gene_name": "BNIP3L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60238" }, "relationship_type": "causal", "source_pmcid": "PMC11202821" }, { "confidence": "high", "disease": "Marfan syndrome", "glycan_involvement": "Fibrillin-1 is a glycoprotein; glycosylation is essential for its proper folding and function.", "mechanism": "Mutations in FBN1 gene lead to defective fibrillin-1, compromising microfibril structure and connective tissue stability.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC11202825" }, { "confidence": "high", "disease": "Dural ectasia", "glycan_involvement": "Glycosylation of fibrillin-1 affects its extracellular matrix assembly.", "mechanism": "Defective fibrillin-1 weakens connective tissue in the dura mater, leading to expansion and bone erosion.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC11202825" }, { "confidence": "high", "disease": "Aortic root dilatation", "glycan_involvement": "Glycosylation status may influence fibrillin-1 stability in the vessel wall.", "mechanism": "Impaired microfibril formation due to mutated fibrillin-1 leads to loss of aortic wall elasticity and dilatation.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC11202825" }, { "confidence": "high", "disease": "Aortic dissection", "glycan_involvement": "Glycosylation may affect fibrillin-1's resistance to mechanical stress.", "mechanism": "Structural weakness from defective fibrillin-1 predisposes to aortic wall rupture.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC11202825" }, { "confidence": "high", "disease": "Ectopia lentis", "glycan_involvement": "Glycosylation is important for fibrillin-1's interaction with other matrix proteins in the eye.", "mechanism": "Defective fibrillin-1 disrupts zonular fibers, causing lens displacement.", "protein": "Fibrillin-1", "relationship_type": "causal", "source_pmcid": "PMC11202825" }, { "confidence": "medium", "disease": "Esophageal Cancer (ESCA)", "glycan_involvement": "Glycosylation affects receptor localization and ligand binding.", "mechanism": "Bile acid signaling via TGR5 modulates cell proliferation and may promote carcinogenesis in esophageal tissue.", "protein": "Gpbar1 (TGR5)", "relationship_type": "causal", "source_pmcid": "PMC11203100" }, { "confidence": "medium", "disease": "Esophageal Cancer (ESCA)", "glycan_involvement": "Glycosylation may regulate receptor stability and nuclear translocation.", "mechanism": "VDR is overexpressed in precancerous and cancerous esophageal lesions, indicating involvement in early carcinogenesis.", "protein": "Vitamin D Receptor (VDR)", "relationship_type": "biomarker", "source_pmcid": "PMC11203100" }, { "confidence": "medium", "disease": "Esophageal Cancer (ESCA)", "glycan_involvement": "Albumin glycosylation status may affect binding to bilirubin and other metabolites.", "mechanism": "Albumin\u2013bilirubin ratio (ALBI score) predicts prognosis in ESCA patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203100" }, { "confidence": "medium", "disease": "Esophageal Cancer (ESCA)", "glycan_involvement": "Glycosylation of albumin influences bilirubin binding and clearance.", "mechanism": "High albumin\u2013bilirubin ratio correlates with poor survival in ESCA.", "protein": "Bilirubin-bound Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation modulates CXCR3 cell surface expression and function.", "mechanism": "1-Arachidonoyl-GPC inhibits migration of CXCR3+ T cells, reducing intestinal inflammation.", "protein": "CXCR3", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling p", "gene_name": "CXCR3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49682" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor activity.", "mechanism": "Bile acid signaling via TGR5 influences energy metabolism and adiposity.", "protein": "Gpbar1 (TGR5)", "relationship_type": "causal", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Impaired Thyroid Function", "glycan_involvement": "Glycosylation may affect albumin\u2019s transport capacity.", "mechanism": "1-arachidonoyl-GPC supplementation linked to impaired thyroid function, possibly via albumin transport.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Benign Neoplasm of Colon", "glycan_involvement": "Glycosylation could regulate VDR function.", "mechanism": "VDR expression may be altered in colon neoplasms.", "protein": "Vitamin D Receptor (VDR)", "relationship_type": "biomarker", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "TGR5 activation by bile acids may protect against mucosal inflammation.", "protein": "Gpbar1 (TGR5)", "relationship_type": "protective", "source_pmcid": "PMC11203100" }, { "confidence": "low", "disease": "Esophageal Cancer (ESCA)", "glycan_involvement": "Glycosylation affects CXCR3-mediated cell trafficking.", "mechanism": "CXCR3+ T cell migration may influence tumor microenvironment and immune response in ESCA.", "protein": "CXCR3", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling p", "gene_name": "CXCR3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49682" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203100" }, { "confidence": "high", "disease": "Neuroendocrine Neoplasms (NENs)", "glycan_involvement": "CgA is an acidic glycoprotein; glycosylation affects stability and secretion.", "mechanism": "CgA is released from neuroendocrine cells; levels correlate with tumor burden and progression.", "protein": "Chromogranin A (CgA)", "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Pancreatic Neuroendocrine Tumors (panNENs)", "glycan_involvement": "PP is glycosylated, which may affect its secretion and detection.", "mechanism": "Elevated PP indicates panNENs; used in combination with CgA for improved sensitivity.", "protein": "Pancreatic Polypeptide (PP)", "protein_enriched": { "function": "Hormone secreted by pancreatic cells that acts as a regulator of pancreatic and gastrointestinal functions probably by signaling through the G protein-coupled receptor NPY4R2", "gene_name": "PPY", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Small-cell Lung Carcinoma", "glycan_involvement": "Minor glycosylation; not central to biomarker function.", "mechanism": "Elevated NSE is indicative of neuroendocrine malignancies, especially small-cell lung carcinoma.", "protein": "Neuron-Specific Enolase (NSE)", "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Zollinger-Ellison Syndrome (ZES)", "glycan_involvement": "Gastrin is glycosylated, which affects its stability and receptor binding.", "mechanism": "Pathological overproduction of gastrin by gastrinoma leads to ZES.", "protein": "Gastrin", "protein_enriched": { "function": "Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circu", "gene_name": "GAST", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01350" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Insulinoma", "glycan_involvement": "Insulin glycosylation affects folding and secretion.", "mechanism": "Insulinomas secrete excess insulin, causing hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Somatostatinoma", "glycan_involvement": "Somatostatin glycosylation may affect hormone stability.", "mechanism": "Somatostatinomas secrete excess somatostatin, leading to diabetes, steatorrhea, and cholelithiasis.", "protein": "Somatostatin", "protein_enriched": { "function": "Inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH. Also impairs ghrelin- and GnRH-stimulated secretion of G", "gene_name": "SST", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P61278" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "VIPoma", "glycan_involvement": "VIP glycosylation affects secretion and activity.", "mechanism": "VIPomas secrete excess VIP, causing secretory diarrhea and metabolic disturbances.", "protein": "Vasoactive Intestinal Peptide (VIP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Medullary Thyroid Cancer", "glycan_involvement": "Calcitonin glycosylation affects stability and detection.", "mechanism": "Elevated calcitonin is a marker for medullary thyroid cancer.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "medium", "disease": "Pancreatic Neuroendocrine Tumors (panNENs)", "glycan_involvement": "Potential glycosylation; functional impact not detailed.", "mechanism": "Upregulation of ACTR3 is associated with panNENs.", "protein": "Actin-related protein 3 (ACTR3)", "protein_enriched": { "function": "F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein", "gene_name": "ACTN2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35609" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "medium", "disease": "Pancreatic Neuroendocrine Tumors (panNENs)", "glycan_involvement": "CD163 is a glycoprotein; glycosylation affects receptor function.", "mechanism": "Upregulation of CD163 is associated with panNENs.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203125" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is N-glycosylated; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Elevated in serum- and CSF-derived EVs from MS patients, correlates with disease activity.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "N-glycosylation modulates ICAM-1 function and cell adhesion.", "mechanism": "EVs carrying ICAM-1 promote monocyte adhesion and transmigration across the BBB, contributing to neuroinflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "N-glycosylation affects VCAM-1-mediated adhesion.", "mechanism": "Upregulated on BBB endothelium, facilitates leukocyte transmigration in MS lesions.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation influences fibrinogen structure and immune interactions.", "mechanism": "EV-associated fibrinogen promotes inflammation, BBB disruption, and lesion formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Fibronectin is glycosylated; glycosylation modulates cell adhesion and matrix interactions.", "mechanism": "EV-derived fibronectin in CSF distinguishes MS from neuromyelitis optica.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "TLR3 is glycosylated, which affects receptor function.", "mechanism": "Lower levels in serum EVs from MS patients; TLR3 may have a protective role.", "protein": "TLR3", "protein_enriched": { "function": "Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a", "gene_name": "TLR3", "glycan_count": 35, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G00912UN", "G59626AS", "G62765YT", "G11314AS", "G23719VF", "G27947YN", "G31852PQ", "G41071NU", "G43669FQ", "G45395BF", "G47644PP", "G70232NH", "G80920RR", "G83460ZZ", "G92275SC", "G95865ZB", "G27058EU", "G37399XV", "G05962QB", "G69521XL", "G37818NZ", "G26436YP", "G22573RC", "G02815KT", "G11101UV", "G26377UA", "G28541PG", "G57489SP", "G63136LV", "G01650EU", "G41247ZX", "G59924QI", "G63041LO", "G96091TT", "G49108TO" ], "uniprot_id": "O15455" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "TLR4 glycosylation is essential for surface expression and signaling.", "mechanism": "Lower levels in serum EVs from MS patients; TLR4 supports inflammatory processes.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "N-glycosylation modulates PECAM-1 function.", "mechanism": "Elevated in plasma EVs during MS exacerbation, marker of acute endothelial injury.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Present in oligodendrocyte-derived EVs; proposed as a marker for MS diagnosis.", "protein": "MBP", "relationship_type": "biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "medium", "disease": "Neuromyelitis optica", "glycan_involvement": "Not a glycoprotein.", "mechanism": "EV-derived GFAP in CSF is associated with neuromyelitis optica, not MS.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203165" }, { "confidence": "high", "disease": "Retinal vein occlusion (RVO)", "glycan_involvement": "PON1 is a glycoprotein; glycosylation may affect stability and activity, but not directly studied here.", "mechanism": "PON1 Q192R polymorphism (R allele) increases risk of RVO, likely via reduced antioxidant/anti-atherogenic activity.", "protein": "Paraoxonase 1 (PON1)", "protein_enriched": { "function": "Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic ", "gene_name": "PON1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G48414YA", "G49108TO", "G00912UN", "G01650EU", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G12793SR", "G15127JD", "G23294PN", "G23453IV", "G24954UD", "G26330YA", "G27947YN", "G31916IQ", "G33791AF", "G37399XV", "G40574BA", "G42358LZ", "G45395BF", "G45504EY", "G47518TP", "G52527GH", "G57776ZU", "G59626AS", "G70232NH", "G72291OX", "G75983OB", "G77547TA", "G78790NZ", "G82463GQ", "G92551JA", "G94470IW", "G95865ZB", "G99679NM", "G03644CB", "G11629QQ", "G14547CB", "G15169WU", "G23010ZW", "G43669FQ", "G56518TU", "G57776ZS", "G67164EE", "G70888PK", "G80075MS", "G85144OK", "G86880BF", "G87123QX", "G90787TS", "G93860XO", "G94917XT" ], "uniprot_id": "P27169" }, "relationship_type": "causal", "source_pmcid": "PMC11203263" }, { "confidence": "medium", "disease": "Central retinal vein occlusion (CRVO)", "glycan_involvement": "Glycosylation may modulate PON1 activity; not directly assessed.", "mechanism": "Lower PON1 arylesterase activity observed in CRVO patients, implicating oxidative stress.", "protein": "Paraoxonase 1 (PON1)", "protein_enriched": { "function": "Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic ", "gene_name": "PON1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G48414YA", "G49108TO", "G00912UN", "G01650EU", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G12793SR", "G15127JD", "G23294PN", "G23453IV", "G24954UD", "G26330YA", "G27947YN", "G31916IQ", "G33791AF", "G37399XV", "G40574BA", "G42358LZ", "G45395BF", "G45504EY", "G47518TP", "G52527GH", "G57776ZU", "G59626AS", "G70232NH", "G72291OX", "G75983OB", "G77547TA", "G78790NZ", "G82463GQ", "G92551JA", "G94470IW", "G95865ZB", "G99679NM", "G03644CB", "G11629QQ", "G14547CB", "G15169WU", "G23010ZW", "G43669FQ", "G56518TU", "G57776ZS", "G67164EE", "G70888PK", "G80075MS", "G85144OK", "G86880BF", "G87123QX", "G90787TS", "G93860XO", "G94917XT" ], "uniprot_id": "P27169" }, "relationship_type": "causal", "source_pmcid": "PMC11203263" }, { "confidence": "low", "disease": "Retinal vein occlusion (RVO)", "glycan_involvement": "APOE is N-glycosylated; glycosylation affects lipid binding and clearance.", "mechanism": "APOE E4 allele previously suggested as risk factor, but no association found in this study.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11203263" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates APOE function.", "mechanism": "APOE E4 allele associated with increased cardiovascular risk due to lower plasma APOE and impaired lipid clearance.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11203263" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation may affect APOE trafficking and function.", "mechanism": "APOE E4 allele is a strong genetic risk factor for Alzheimer's due to decreased amyloid clearance.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11203263" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation may influence APOE deposition in retinal drusen.", "mechanism": "APOE E4 allele linked to protection in AMD, possibly due to local retinal expression.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective", "source_pmcid": "PMC11203263" }, { "confidence": "high", "disease": "Ocular neovascularisation", "glycan_involvement": "SDF-1 is glycosylated; glycosylation may affect secretion and receptor binding.", "mechanism": "SDF-1 upregulation promotes angiogenesis and neovascularisation via CXCR4/VEGF pathway.", "protein": "Stromal cell-derived factor 1 (SDF-1/CXCL12)", "relationship_type": "causal", "source_pmcid": "PMC11203263" }, { "confidence": "medium", "disease": "Retinal vein occlusion (RVO)", "glycan_involvement": "Glycosylation may regulate SDF-1 function in retina.", "mechanism": "SDF-1 vitreous levels higher in RVO with neovascularisation; SDF1-3\u2032(801)A allele may predispose to neovascular complications.", "protein": "Stromal cell-derived factor 1 (SDF-1/CXCL12)", "relationship_type": "biomarker", "source_pmcid": "PMC11203263" }, { "confidence": "low", "disease": "Retinal vein occlusion (RVO)", "glycan_involvement": "Glycosylation could be targeted to enhance PON1 stability/activity.", "mechanism": "PON1 activity modulation may reduce oxidative stress and RVO risk.", "protein": "Paraoxonase 1 (PON1)", "protein_enriched": { "function": "Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic ", "gene_name": "PON1", "glycan_count": 55, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G48414YA", "G49108TO", "G00912UN", "G01650EU", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G12793SR", "G15127JD", "G23294PN", "G23453IV", "G24954UD", "G26330YA", "G27947YN", "G31916IQ", "G33791AF", "G37399XV", "G40574BA", "G42358LZ", "G45395BF", "G45504EY", "G47518TP", "G52527GH", "G57776ZU", "G59626AS", "G70232NH", "G72291OX", "G75983OB", "G77547TA", "G78790NZ", "G82463GQ", "G92551JA", "G94470IW", "G95865ZB", "G99679NM", "G03644CB", "G11629QQ", "G14547CB", "G15169WU", "G23010ZW", "G43669FQ", "G56518TU", "G57776ZS", "G67164EE", "G70888PK", "G80075MS", "G85144OK", "G86880BF", "G87123QX", "G90787TS", "G93860XO", "G94917XT" ], "uniprot_id": "P27169" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203263" }, { "confidence": "low", "disease": "Retinal vein occlusion (RVO)", "glycan_involvement": "N-glycosylation influences APOE anti-inflammatory function.", "mechanism": "APOE anti-inflammatory effects may protect against RVO, but not supported by current study.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective", "source_pmcid": "PMC11203263" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Heavy O-glycosylation; underglycosylation in cancer cells promotes pathological interactions.", "mechanism": "Aberrant expression and altered glycosylation of MUC1 serve as a biomarker for pancreatic cancer.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203369" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Underglycosylation in cancer cells enhances MUC1 interactions with receptors and ECM.", "mechanism": "MUC1 overexpression induces resistance to chemotherapy and ionizing radiation by upregulating NHEJ and suppressing HR.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203369" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Altered glycosylation affects MUC1's cellular localization and signaling.", "mechanism": "MUC1 overexpression causes metabolic reprogramming, increases dNTP pools, stimulates NHEJ, suppresses HR, and promotes genetic instability.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11203369" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation status influences MUC1's role in repair pathway imbalance.", "mechanism": "MUC1-overexpressed pancreatic cancer cells are selectively killed by DNA-PK and HDAC1/2 inhibitors due to NHEJ dependency.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203369" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Not directly specified for this mechanism.", "mechanism": "MUC1 suppresses BRCA1 transcription, leading to HR deficiency and increased reliance on NHEJ.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11203369" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Not directly specified for this mechanism.", "mechanism": "MUC1-induced HR deficiency sensitizes cells to RAD52 inhibitors (synthetic lethality).", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203369" }, { "confidence": "low", "disease": "Pancreatic cancer", "glycan_involvement": "Not directly specified for this mechanism.", "mechanism": "MUC1 stabilizes HIF1a, potentially suppressing HR genes under hypoxia.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11203369" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Altered glycosylation may affect metabolic regulation.", "mechanism": "MUC1 overexpression increases dNTP pools, directly stimulating mutagenic NHEJ and promoting genetic instability.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11203369" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Extensive O-glycosylation of extracellular domain.", "mechanism": "Normal MUC1 O-glycosylation protects epithelial surfaces from pathogens.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "protective", "source_pmcid": "PMC11203369" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Reduced O-glycosylation increases pathological interactions.", "mechanism": "Underglycosylated MUC1 in cancer cells promotes interaction with transmembrane receptors and ECM, facilitating tumor progression.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC11203369" }, { "confidence": "high", "disease": "Hypoxia-induced stress", "glycan_involvement": "HIF-1\u03b1 is glycosylated, which may affect stability and function", "mechanism": "Upregulated in response to hypoxia, activates hypoxia-adaptive genes", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "high", "disease": "Hypoxia-induced stress", "glycan_involvement": "Likely glycosylated, may influence protein stability", "mechanism": "Upregulated under hypoxia, regulates erythropoietin and vascular genes", "protein": "HIF-2\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Hypoxia-induced stress", "glycan_involvement": "Possible glycosylation, functional impact unclear", "mechanism": "Induced by acute hypoxia, role less clear", "protein": "HIF-3\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "high", "disease": "Hypoxia-induced stress", "glycan_involvement": "N-glycosylation required for membrane localization and function", "mechanism": "Upregulated by HIF pathway, increases glucose uptake under hypoxia", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "high", "disease": "Hypoxia-induced stress", "glycan_involvement": "N-glycosylation essential for secretion and receptor binding", "mechanism": "Upregulated by HIFs, promotes angiogenesis in response to hypoxia", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Impaired metabolism/Impaired immune function", "glycan_involvement": "Glycosylation affects enzyme stability and activity", "mechanism": "Decreased activity under severe hypoxia, indicating metabolic and immune dysfunction", "protein": "AKP", "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Myocardial injury", "glycan_involvement": "Possible glycosylation, may affect enzyme release", "mechanism": "Increased serum activity after hypoxia, marker of tissue damage", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Myocardial injury", "glycan_involvement": "Possible glycosylation, functional impact not detailed", "mechanism": "Increased serum activity after hypoxia, marker of myocardial damage", "protein": "HBDH", "relationship_type": "biomarker", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Hypoxia-induced stress", "glycan_involvement": "Possible glycosylation, may affect protein-protein interactions", "mechanism": "Downregulated under hypoxia, leading to HIF stabilization", "protein": "VHL", "relationship_type": "causal", "source_pmcid": "PMC11203381" }, { "confidence": "medium", "disease": "Hypoxia-induced stress", "glycan_involvement": "Possible glycosylation, impact not specified", "mechanism": "Upregulated under hypoxia, modulates HIF degradation", "protein": "PHD2", "relationship_type": "regulatory", "source_pmcid": "PMC11203381" }, { "confidence": "high", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Glycosylation may affect trafficking and stability, but not detailed in article.", "mechanism": "Dephosphorylation and redistribution of Cx43 reduces gap junction conductivity, impairing impulse conduction and promoting arrhythmia post-MI.", "protein": "Connexin43 (Cx43)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203447" }, { "confidence": "high", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation modulates channel expression and gating.", "mechanism": "Upregulation of Nav1.5 reduces arrhythmia risk post-MI; phosphorylation and glycosylation regulate channel density and kinetics.", "protein": "Nav1.5 (SCN5A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Beta subunits are glycoproteins; glycosylation affects folding and cell surface expression.", "mechanism": "Beta subunits regulate Na+ channel density and dynamics, influencing conduction velocity after MI.", "protein": "Nav beta subunits (SCN1B-SCN4B)", "relationship_type": "biomarker", "source_pmcid": "PMC11203447" }, { "confidence": "high", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Glycosylation may affect channel trafficking and function.", "mechanism": "Reduced expression of \u03b11c and \u03b22c subunits after MI leads to decreased Ca2+-induced Ca2+ release and systolic dysfunction.", "protein": "Cav1.2 (CACNA1C)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Not specified.", "mechanism": "Knockout of Cav3.1 exacerbates arrhythmias and decreases contractility after MI.", "protein": "Cav3.1 (CACNA1G)", "protein_enriched": { "function": "S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methyluridine at position 1369 (Um1369) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU", "gene_name": "MRM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UI43" }, "relationship_type": "causal", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Not specified.", "mechanism": "TREK-1 protects against ischemia-induced damage; knockout leads to prolonged QT interval and APD.", "protein": "TREK-1 (KCNK2)", "relationship_type": "protective", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Ischemia/Reperfusion Injury", "glycan_involvement": "Not specified.", "mechanism": "Upregulation of TRPV1 increases apoptosis and Ca2+ overload, worsening I/R injury.", "protein": "TRPV1", "protein_enriched": { "function": "Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:11050376, PubMed:11243859, PubMed:11226139, PubMed:12077606). Seems to mediate proto", "gene_name": "TRPV1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NER1" }, "relationship_type": "causal", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Cardiac Fibrosis", "glycan_involvement": "Not specified.", "mechanism": "TRPM4 deletion enhances pro-inflammatory response and accelerates fibrosis post-MI.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "Not specified.", "mechanism": "Macrophage KCa3.1 activation modulates cardiomyocyte electrophysiology, predisposing to arrhythmia post-MI.", "protein": "KCa3.1 (KCNN4)", "protein_enriched": { "function": "Intermediate conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with ", "gene_name": "KCNN4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15554" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203447" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Not specified.", "mechanism": "Kv1.3 activation in T cells enhances cytokine secretion via CaN/NFAT pathway, triggering microinflammatory response and hypertension.", "protein": "Kv1.3 (KCNA3)", "relationship_type": "causal", "source_pmcid": "PMC11203447" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "VDR activation by vitamin D analogs induces differentiation and apoptosis in cancer cells.", "protein": "Vitamin D Receptor (VDR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203455" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "VDR agonists (e.g., calcipotriol) reduce hyperproliferation of keratinocytes.", "protein": "Vitamin D Receptor (VDR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203455" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "CD14 is a membrane-anchored glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "1,25(OH)2D3 upregulates CD14, enhancing innate immune response to Mycobacterium tuberculosis.", "protein": "Cluster of Differentiation 14 (CD14)", "relationship_type": "protective", "source_pmcid": "PMC11203455" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "Cathelicidin is glycosylated, which may affect stability and secretion.", "mechanism": "Vitamin D induces cathelicidin expression, promoting antimicrobial activity against tuberculosis.", "protein": "Cathelicidin", "relationship_type": "protective", "source_pmcid": "PMC11203455" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Defensins are glycoproteins; glycosylation may modulate activity.", "mechanism": "Vitamin D induces defensin expression, enhancing antimicrobial defense.", "protein": "Defensin", "relationship_type": "protective", "source_pmcid": "PMC11203455" }, { "confidence": "high", "disease": "Rickets", "glycan_involvement": "PTH is glycosylated, which is important for secretion and stability.", "mechanism": "Vitamin D deficiency leads to increased PTH, causing bone demineralization and rickets.", "protein": "Parathyroid Hormone (PTH)", "relationship_type": "causal", "source_pmcid": "PMC11203455" }, { "confidence": "medium", "disease": "Renal Osteodystrophy", "glycan_involvement": "Osteopontin glycosylation modulates cell adhesion and signaling.", "mechanism": "Vitamin D regulates osteopontin expression, affecting bone remodeling in renal osteodystrophy.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC11203455" }, { "confidence": "medium", "disease": "Renal Osteodystrophy", "glycan_involvement": "Osteocalcin is glycosylated, affecting its function in bone.", "mechanism": "Vitamin D regulates osteocalcin, influencing bone matrix formation.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203455" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Thrombomodulin glycosylation is critical for endothelial function.", "mechanism": "Vitamin D increases thrombomodulin, reducing coagulation and inflammation in hypertension.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11203455" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "PDIA3 is glycosylated; glycosylation may influence membrane localization and receptor function.", "mechanism": "PDIA3 acts as a membrane receptor for vitamin D, mediating rapid signaling and affecting cancer cell differentiation.", "protein": "PDIA3 (GRP58/ERp57)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203455" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Low ceruloplasmin due to ATP7B mutation impairs copper transport, leading to hepatic copper accumulation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203474" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "ATP7B is glycosylated; glycosylation may affect trafficking and function.", "mechanism": "ATP7B mutation disrupts copper excretion via bile, causing copper buildup in liver and other organs.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal", "source_pmcid": "PMC11203474" }, { "confidence": "high", "disease": "Hemochromatosis", "glycan_involvement": "Transferrin glycosylation influences iron binding and clearance.", "mechanism": "Transferrin saturation is used to diagnose iron overload in hemochromatosis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203474" }, { "confidence": "medium", "disease": "Acute copper intoxication", "glycan_involvement": "Albumin glycosylation modulates binding affinity for copper.", "mechanism": "Albumin binds free copper, reducing toxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC11203474" }, { "confidence": "high", "disease": "Non-immune hemolytic anemia (in Wilson disease and copper intoxication)", "glycan_involvement": "Haptoglobin glycosylation affects hemoglobin binding and clearance.", "mechanism": "Low haptoglobin indicates hemolysis due to copper toxicity.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203474" }, { "confidence": "high", "disease": "Copper/iron/cadmium/arsenic toxicity", "glycan_involvement": "Not glycosylated.", "mechanism": "Metallothionein binds heavy metals, reducing cellular toxicity.", "protein": "Metallothionein", "relationship_type": "protective", "source_pmcid": "PMC11203474" }, { "confidence": "medium", "disease": "Idiopathic copper toxicosis/childhood cirrhosis", "glycan_involvement": "Glycosylation affects ceruloplasmin stability and diagnostic accuracy.", "mechanism": "Normal/elevated ceruloplasmin distinguishes idiopathic copper toxicosis from Wilson disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203474" }, { "confidence": "medium", "disease": "Copper toxicity", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "SOD1 uses copper as a cofactor to detoxify reactive oxygen species.", "protein": "Superoxide dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC11203474" }, { "confidence": "medium", "disease": "Copper deficiency/toxicity", "glycan_involvement": "Glycosylation affects assembly and activity.", "mechanism": "Copper is essential for cytochrome c oxidase function in mitochondrial respiration; deficiency or excess impairs energy metabolism.", "protein": "Cytochrome c oxidase", "relationship_type": "causal", "source_pmcid": "PMC11203474" }, { "confidence": "low", "disease": "Drug-induced liver injury (DILI)/Herb-induced liver injury (HILI)", "glycan_involvement": "Glycosylation changes may occur during liver injury.", "mechanism": "Altered ceruloplasmin levels may reflect hepatic injury from drugs/herbs.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203474" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Acts via glycosylated receptors (TNFR-1, TNFR-2); receptor glycosylation modulates affinity and signaling.", "mechanism": "Early and sustained increase in TNF-\u03b1 drives neuroinflammation and tissue injury; also has neuroprotective roles.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Degree of glycosylation alters receptor affinity for TNF-\u03b1.", "mechanism": "TNFR-1 mediates TNF-\u03b1-induced neuroinflammation and cell death; glycosylation affects ligand binding.", "protein": "TNFR-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Acts via glycosylated IL-1R; receptor glycosylation modulates signaling.", "mechanism": "IL-1\u03b2 promotes neuroinflammation, edema, and worsens injury; knockout reduces damage.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation status affects receptor function and ligand binding.", "mechanism": "IL-1R mediates IL-1\u03b2 signaling; inhibition reduces infarct size.", "protein": "IL-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "IL-6 increases acutely post-stroke; may have neuroprotective effects in late phase.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11203482" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "IFN-\u03b3 promotes atherogenesis and is upregulated in atherosclerotic lesions, contributing to stroke risk.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "TGF-\u03b21 suppresses neuroinflammation, promotes tissue repair and healing post-stroke.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Stroke Recurrence", "glycan_involvement": "CD28 is a glycoprotein; glycosylation affects cell surface expression and function.", "mechanism": "CD4+CD28 null T cells are increased in stroke patients and predict recurrence and severity.", "protein": "CD28", "protein_enriched": { "function": "Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals b", "gene_name": "CD28", "glycan_count": 4, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G31852PQ", "G41247ZX", "G59626AS" ], "uniprot_id": "P10747" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203482" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "KIRs are glycoproteins; glycosylation modulates receptor-ligand interactions.", "mechanism": "Proinflammatory KIR gene activation increases risk and severity of ischemic stroke via immune cell activation.", "protein": "KIRs", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for cytokine secretion and receptor binding.", "mechanism": "IFN-\u03b3 polarizes microglia to M1 phenotype, increasing neuroinflammation and tissue damage.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC11203482" }, { "confidence": "high", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "High glycosylation form is less expressed in Jurkat T-ALL cells; glycosylation affects antibody binding and function.", "mechanism": "CD147 is overexpressed in T-ALL and promotes tumor proliferation, invasion, and chemoresistance.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203531" }, { "confidence": "high", "disease": "Solid tumors", "glycan_involvement": "Glycosylation state modulates CD147 dimerization and function.", "mechanism": "CD147 upregulation promotes tumor proliferation, invasion, metastasis, and chemoresistance.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203531" }, { "confidence": "medium", "disease": "Cutaneous T cell lymphoma", "glycan_involvement": "Not specified", "mechanism": "CD147 interaction with cyclophilin promotes proliferation and survival.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "causal", "source_pmcid": "PMC11203531" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Epitope overlaps with dimerization region, which is glycosylation-dependent.", "mechanism": "Anti-CD147 antibody (Metuximab) inhibits invasion and metastasis by blocking dimerization.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203531" }, { "confidence": "high", "disease": "General cancer metastasis", "glycan_involvement": "Glycosylation is required for dimerization and MMP induction.", "mechanism": "CD147 dimerization induces MMPs, promoting invasion and metastasis.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "causal", "source_pmcid": "PMC11203531" }, { "confidence": "high", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "Glycosylation affects antibody recognition.", "mechanism": "CD147 is upregulated in T-ALL and can be targeted by antibodies for diagnosis or therapy.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "biomarker", "source_pmcid": "PMC11203531" }, { "confidence": "high", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "Antibody binding is influenced by CD147 glycosylation state.", "mechanism": "Anti-CD147 antibody (HuM6-1B9/Takatamab) enhances macrophage-mediated phagocytosis of T-ALL cells.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203531" }, { "confidence": "medium", "disease": "General cancer", "glycan_involvement": "Not specified", "mechanism": "CD147 is required for recruitment and accumulation of monocytic myeloid-derived suppressor cells (mMDSCs), which suppress anti-tumor immunity.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "causal", "source_pmcid": "PMC11203531" }, { "confidence": "medium", "disease": "Acute lymphoblastic leukemia", "glycan_involvement": "Not specified", "mechanism": "MMP-2, induced by CD147, is involved in leukemia cell extravasation.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "causal", "source_pmcid": "PMC11203531" }, { "confidence": "medium", "disease": "T-cell leukemia", "glycan_involvement": "Not specified", "mechanism": "MMP-9 elevation is associated with T cell infiltration in leukemia.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC11203531" }, { "confidence": "high", "disease": "NSMP EC", "glycan_involvement": "L1CAM is a heavily glycosylated cell adhesion molecule; glycosylation affects its adhesive and migratory properties.", "mechanism": "L1CAM mutation is associated with migration of cancer cells and poor survival in NSMP EC.", "protein": "L1 cell adhesion molecule (L1CAM)", "relationship_type": "biomarker", "source_pmcid": "PMC11203539" }, { "confidence": "high", "disease": "Endometrial cancer (EC)", "glycan_involvement": "CTNND1 is glycosylated, which may modulate its cell adhesion function.", "mechanism": "circRNA hsa_circ_0002577 sponges miR-197, upregulating CTNND1 and activating Wnt/\u03b2-catenin signaling, promoting proliferation and invasion.", "protein": "CTNND1 (delta-catenin)", "protein_enriched": { "function": "Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:", "gene_name": "CTNND1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59324HL", "G23221TW", "G31596VW", "G56284ZY", "G49108TO" ], "uniprot_id": "O60716" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Chemoresistant EC", "glycan_involvement": "IGF2BP1 is a glycoprotein; glycosylation may affect its stability and RNA-binding activity.", "mechanism": "circ_0005667 sponges miR-145-5p, increasing IGF2BP1, leading to cisplatin resistance.", "protein": "IGF2BP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Endometrial cancer (EC)", "glycan_involvement": "PDGFRB is N-glycosylated, which is essential for receptor function and signaling.", "mechanism": "circCHD7 interacts with IGF2BP2, increasing PDGFRB mRNA and activating JAK/STAT pathway, promoting proliferation.", "protein": "PDGFRB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Endometrial cancer (EC)", "glycan_involvement": "HMGA1 is not a classical glycoprotein but may interact with glycosylated nuclear proteins.", "mechanism": "circRNA hsa_circ_0039569 sponges miR-197, upregulating HMGA1, promoting proliferation and invasion.", "protein": "HMGA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Endometrial cancer (EC)", "glycan_involvement": "RBFOX2 is not a classical glycoprotein; glycosylation not directly implicated.", "mechanism": "circRAPGEF5 binds RBFOX2, impairs its pre-mRNA binding, leading to ferroptosis resistance.", "protein": "RBFOX2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Metastatic EC", "glycan_involvement": "Smad4 is glycosylated; glycosylation may affect its nuclear localization and transcriptional activity.", "mechanism": "miR-27a-5p upregulated in PCOS, promotes EC cell migration/invasion via Smad4.", "protein": "Smad4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "low", "disease": "Endometrial cancer (EC)", "glycan_involvement": "MBNL1 is not a classical glycoprotein; glycosylation not directly implicated.", "mechanism": "MBNL1 regulates circRNA biogenesis via RBP-mediated splicing, influencing EC progression.", "protein": "MBNL1", "relationship_type": "causal", "source_pmcid": "PMC11203539" }, { "confidence": "medium", "disease": "Endometrial cancer (EC)", "glycan_involvement": "IGFBP2 is glycosylated; glycosylation affects its binding to IGFs and stability.", "mechanism": "circCHD7 interacts with IGFBP2, increasing PDGFRB and activating proliferation.", "protein": "IGFBP2", "protein_enriched": { "function": "Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proli", "gene_name": "IGFBP2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "P18065" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203539" }, { "confidence": "high", "disease": "Type I EC", "glycan_involvement": "EGFR is N-glycosylated; glycosylation is critical for ligand binding and receptor activation.", "mechanism": "Estradiol activates EGFR, leading to PI3K/AKT/mTOR pathway activation and carcinogenesis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC11203539" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation may affect its processing and trafficking.", "mechanism": "APP is sequentially cleaved by \u03b2- and \u03b3-secretases to produce A\u03b2 peptides, which aggregate and form plaques characteristic of Alzheimer's disease.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; A\u03b2 interacts with membrane glycosphingolipids (gangliosides) during aggregation.", "mechanism": "A\u03b242 aggregates to form extracellular plaques, leading to synaptic dysfunction, neuronal stress, tau pathology, and cell death.", "protein": "A\u03b2 peptide (A\u03b242)", "relationship_type": "causal", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GM1's sialylated glycan headgroup acts as a scaffold for A\u03b2 binding.", "mechanism": "GM1 facilitates A\u03b242 binding to membranes and accelerates its aggregation and \u03b2-sheet formation.", "protein": "Ganglioside GM1", "relationship_type": "causal", "source_pmcid": "PMC11203662" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sialylated glycan headgroup mediates A\u03b2 interaction.", "mechanism": "GT1b enhances A\u03b242 membrane binding and aggregation, similar to GM1.", "protein": "Ganglioside GT1b", "relationship_type": "causal", "source_pmcid": "PMC11203662" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycan moieties provide negative charge and H-bonding for A\u03b2 anchoring.", "mechanism": "Brain gangliosides facilitate A\u03b242 membrane binding and aggregation.", "protein": "Total brain gangliosides", "relationship_type": "causal", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is glycosylated; glycosylation may affect its localization and activity.", "mechanism": "\u03b2-secretase cleaves APP, initiating A\u03b2 production; its activity is associated with lipid raft domains.", "protein": "\u03b2-secretase (BACE1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Complex is glycosylated; glycosylation may influence assembly and function.", "mechanism": "\u03b3-secretase further cleaves APP to produce A\u03b2 peptides.", "protein": "\u03b3-secretase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203662" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sphingomyelin is a glycolipid; its headgroup may participate in A\u03b2 interaction.", "mechanism": "Sphingomyelin-rich domains modulate A\u03b242 membrane binding and aggregation.", "protein": "Sphingomyelin", "relationship_type": "modulatory", "source_pmcid": "PMC11203662" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not glycosylated; effect is electrostatic.", "mechanism": "Negatively charged phosphatidic acid enhances A\u03b242 membrane insertion and aggregation.", "protein": "Phosphatidic acid", "relationship_type": "modulatory", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Indirect; interaction with membrane glycans influences aggregation.", "mechanism": "A\u03b242 levels and aggregation state serve as biomarkers for Alzheimer's disease progression.", "protein": "A\u03b2 peptide (A\u03b242)", "relationship_type": "biomarker", "source_pmcid": "PMC11203662" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CLU is a heavily glycosylated protein; glycosylation affects its chaperone and clearance functions.", "mechanism": "CLU modulates A\u03b2 aggregation and clearance; excess A\u03b2 leads to toxic CLU-containing amyloid aggregates.", "protein": "Clusterin (CLU)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203688" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "GPIIb/IIIa is glycosylated; glycosylation is essential for receptor function and ligand binding.", "mechanism": "Promotes CLU release from platelets in response to A\u03b2, facilitating A\u03b2 aggregation.", "protein": "Integrin \u03b1IIb\u03b23 (GPIIb/IIIa)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203688" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP glycosylation modulates processing and A\u03b2 generation.", "mechanism": "Platelets process APP into A\u03b2 peptides, which aggregate and deposit in the brain.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11203688" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "P-selectin glycosylation is required for ligand binding and cell adhesion.", "mechanism": "Platelet activation marker; elevated in AD and correlates with cognitive decline.", "protein": "P-selectin (CD62P)", "relationship_type": "biomarker", "source_pmcid": "PMC11203688" }, { "confidence": "medium", "disease": "Cerebral amyloid angiopathy (CAA)", "glycan_involvement": "Glycosylation affects CLU's anti-amyloid and anti-atherosclerotic functions.", "mechanism": "CLU modulates cholesterol transport and protects against vascular amyloid deposition.", "protein": "Clusterin (CLU)", "relationship_type": "protective/causal", "source_pmcid": "PMC11203688" }, { "confidence": "high", "disease": "Glanzmann's thrombasthenia", "glycan_involvement": "Loss of glycosylated receptor disrupts function.", "mechanism": "Deficiency impairs platelet aggregation and A\u03b2 fibril formation.", "protein": "Integrin \u03b1IIb\u03b23 (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC11203688" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "HMGB1 is glycosylated; glycosylation may affect extracellular signaling.", "mechanism": "Released by activated platelets; promotes neuroinflammation and cellular senescence.", "protein": "High-mobility group box 1 (HMGB1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203688" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Decreased platelet GSK3B ratio correlates with cognitive impairment.", "protein": "Glycogen synthase kinase 3-beta (GSK3B)", "relationship_type": "biomarker", "source_pmcid": "PMC11203688" }, { "confidence": "low", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Platelet activation marker; potential for staging MCI.", "protein": "P-selectin (CD62P)", "relationship_type": "biomarker", "source_pmcid": "PMC11203688" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "VWF is highly glycosylated; glycosylation modulates platelet binding.", "mechanism": "Platelet glycoproteins interact with VWF during clot formation.", "protein": "Von Willebrand factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC11203688" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "O-glycosylation of hydroxylysine stabilizes fibrils and affects deposition.", "mechanism": "Excessive deposition drives fibrotic tissue formation; targeted by collagenases and anti-fibrotic drugs.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-glycosylation modulates fibril assembly and ECM interactions.", "mechanism": "Expression reduces metastasis and induces cancer cell quiescence in breast cancer models.", "protein": "Collagen III", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A2", "glycan_count": 18, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G25637MV", "G27915IV", "G31852PQ", "G39188ZX", "G40574BA", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G43417UB", "G49108TO" ], "uniprot_id": "P08123" }, "relationship_type": "protective", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-glycosylation and sulfilimine crosslinks critical for network stability.", "mechanism": "Altered secretion and assembly in epithelial tumors supports EMT and tumor survival.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Hemostasis Disorders", "glycan_involvement": "N-glycosylation required for VWF stability and function.", "mechanism": "Binds collagen I/III/IV/VI to mediate platelet adhesion; deficiency leads to bleeding disorders.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11203716" }, { "confidence": "medium", "disease": "Wound Healing", "glycan_involvement": "N-glycosylation modulates FN-collagen interactions.", "mechanism": "Collagen-binding domain promotes wound healing and tissue repair.", "protein": "Fibronectin (FN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "O-glycosylation of hydroxylysine by LH2 affects collagen crosslinking.", "mechanism": "Upregulation drives EMT, ECM remodeling, and metastasis; inhibition reduces invasiveness.", "protein": "Lysyl hydroxylase 2 (LH2/PLOD2)", "protein_enriched": { "function": "Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular", "gene_name": "PLOD2", "glycan_count": 45, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G31852PQ", "G35253PZ", "G39471UU", "G61256FT", "G62765YT", "G63381RX", "G64527OM", "G70101JE", "G72667IM", "G76295SF", "G78787DI", "G80920RR", "G83460ZZ", "G49108TO", "G41247ZX", "G02815KT", "G05049YU", "G15664MX", "G23719VF", "G46503DX", "G72747WU", "G83633GK", "G85554PZ", "G90659AW", "G96430BV", "G34730YF", "G37399XV", "G37412TK", "G39188ZX", "G60033FS", "G67324HN", "G00912UN", "G05724UK", "G06110VR", "G20706XG", "G28681TP", "G36379GD", "G50282JC", "G59626AS", "G77547TA", "G80479JV", "G90575OW", "G92050GC", "G92275SC", "G14669DU" ], "uniprot_id": "O00469" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Direct O-glycosylation of collagen hydroxylysines.", "mechanism": "O-glycosylation of collagen hydroxylysines; downregulation impairs collagen deposition and fibrosis.", "protein": "GLT25D1 (COLGALT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "N-glycosylation may affect ER localization and function.", "mechanism": "Chaperone required for collagen folding; inhibition reduces collagen secretion and fibrosis.", "protein": "Heat Shock Protein 47 (HSP47)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Derived from glycosylated collagen IV; glycosylation may affect release/activity.", "mechanism": "Antiangiogenic matrikine inhibits tumor vascularization via integrin binding.", "protein": "Tumstatin (Collagen IV \u03b13 NC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "medium", "disease": "Wound Healing", "glycan_involvement": "Proteoglycan with glycosaminoglycan chains (keratan sulfate) modulating collagen interaction.", "mechanism": "Binds collagen fibers, strengthens ECM, and promotes healing.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203716" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Changes in Fc N-glycosylation modulate IgG effector functions and inflammation.", "mechanism": "Altered IgG Fc N-glycosylation pattern (increased fucosylation, \u03b11,3-galactosylation, decreased sialylation) correlates with sepsis progression and severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Neutrophil-associated enzymes alter glycan exposure (fucose, sialic acid) on IgG.", "mechanism": "Neutrophil activity (including NETs and NE) drives changes in IgG Fc glycosylation during sepsis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11203722" }, { "confidence": "medium", "disease": "Meningococcal sepsis", "glycan_involvement": "Specific glycan traits (galactosylation, \u03b11,3-galactosylation) are altered.", "mechanism": "Altered IgG Fc N-glycosylation (sialylation/galactosylation ratio) associates with disease severity and outcome.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "medium", "disease": "Inflammatory autoimmune conditions", "glycan_involvement": "Altered glycosylation modulates pro- or anti-inflammatory IgG activity.", "mechanism": "Unique N-glycosylation patterns in IgG Fc region are associated with inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "low", "disease": "Coronavirus infection", "glycan_involvement": "Altered glycosylation may affect immune response.", "mechanism": "Changes in IgG Fc N-glycosylation observed in infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "low", "disease": "Inflammatory arthritis", "glycan_involvement": "Modulates IgG function in inflammation.", "mechanism": "Fc N-glycosylation changes are linked to disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Potential impact on immune regulation.", "mechanism": "Altered IgG Fc N-glycosylation observed.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "low", "disease": "Inflammatory bowel disease", "glycan_involvement": "May influence inflammation.", "mechanism": "Changes in IgG glycosylation profile associated with disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "low", "disease": "Active tuberculosis", "glycan_involvement": "Potential role in immune response.", "mechanism": "Altered IgG Fc N-glycosylation profile observed.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203722" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "NE (and NETs) may mediate glycan trimming/exposure on IgG.", "mechanism": "Increased NE activity correlates with late-stage sepsis and altered IgG glycosylation.", "protein": "Neutrophil Elastase (NE)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203722" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry via ACE2 binding and endocytosis.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation not directly discussed; E is a small glycoprotein.", "mechanism": "Viroporin activity critical for viral replication, assembly, and virulence.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "high", "disease": "Neurological dysfunction (neuro-COVID)", "glycan_involvement": "No direct glycan mechanism described for E protein in neurons.", "mechanism": "Induces Ca2+ release from ER, leading to apoptosis in aged neurons and contributing to neurological damage.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "No direct glycan mechanism described.", "mechanism": "Ion channel activity triggers inflammasome activation and cytokine release (IL-1\u03b2, TNF, IL-6), promoting lung damage.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "Parkinsonism", "glycan_involvement": "No direct glycan mechanism described.", "mechanism": "Neuroinvasive properties may contribute to olfactory dysfunction and parkinsonism post-COVID.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycan mechanism described.", "mechanism": "Viroporin activity forms Ca2+-permeable channels, contributing to replication and virulence.", "protein": "SARS-CoV-2 ORF3a protein", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "No direct glycan mechanism described.", "mechanism": "E protein-induced apoptosis in aged neurons resembles amyloid-\u03b2 neurotoxicity in Alzheimer\u2019s models.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal (model comparison)", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "Neurological dysfunction (neuro-COVID)", "glycan_involvement": "No direct glycan mechanism described.", "mechanism": "Targeting E protein viroporin activity may reduce neuronal apoptosis and neuroinflammation.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status not discussed.", "mechanism": "Essential for viral morphogenesis and assembly.", "protein": "SARS-CoV-2 Membrane protein (M)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status not discussed.", "mechanism": "Crucial for viral RNA replication and transcription.", "protein": "SARS-CoV-2 Nucleocapsid protein (N)", "relationship_type": "causal", "source_pmcid": "PMC11203731" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Leptin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated leptin levels correlate with MASLD progression and insulin resistance; hyperleptinemia is associated with hepatic lipid accumulation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "LEPR is glycosylated; glycosylation modulates receptor folding and cell surface expression.", "mechanism": "Increased LEPR expression in liver and omental adipose tissue correlates with MASLD and progression to MASH, indicating peripheral leptin resistance.", "protein": "Leptin receptor (LEPR)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement reported for SOCS3.", "mechanism": "SOCS3 upregulation inhibits leptin and insulin signaling, promoting hepatic steatosis and inflammation.", "protein": "Suppressor of cytokine signaling 3 (SOCS3)", "protein_enriched": { "function": "SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/ST", "gene_name": "SOCS3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14543" }, "relationship_type": "causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Leptin glycosylation affects its bioactivity.", "mechanism": "Higher leptin levels in serum and adipose tissue are associated with progression from MASLD to MASH and increased inflammation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "LEPR glycosylation is required for proper receptor function.", "mechanism": "LEPR protein and mRNA are upregulated in liver and omental adipose tissue in MASH, indicating advanced leptin resistance.", "protein": "Leptin receptor (LEPR)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "No direct glycosylation involvement reported for SOCS3.", "mechanism": "SOCS3 expression in liver and omental adipose tissue correlates with insulin resistance and liver inflammation in MASH.", "protein": "SOCS3", "relationship_type": "causal", "source_pmcid": "PMC11203746" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement reported for SCD1.", "mechanism": "SCD1 upregulation in liver promotes lipid droplet formation and steatosis; correlates with leptin and SOCS3 expression.", "protein": "SCD1", "relationship_type": "causal", "source_pmcid": "PMC11203746" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement reported for PNPLA2.", "mechanism": "PNPLA2 expression in liver correlates with fat mass, waist circumference, and serum leptin, indicating compensatory lipolysis in MASLD.", "protein": "PNPLA2", "relationship_type": "biomarker", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Leptin glycosylation may affect receptor binding and signaling.", "mechanism": "Leptin resistance in adipose tissue and liver is associated with insulin resistance and metabolic dysfunction.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "LEPR glycosylation is essential for receptor trafficking and function.", "mechanism": "LEPR upregulation in obesity reflects compensatory response to hyperleptinemia and leptin resistance.", "protein": "LEPR", "relationship_type": "causal", "source_pmcid": "PMC11203746" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "OPG is a glycoprotein; glycosylation required for secretion and function.", "mechanism": "OPG is essential for Ang II-induced endothelial dysfunction; OPG knockout protects against this effect.", "protein": "Osteoprotegerin", "relationship_type": "causal", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation supports OPG's receptor binding and stability.", "mechanism": "OPG promotes inflammation, leukocyte adhesion, and AT1 receptor expression, contributing to atherogenesis.", "protein": "Osteoprotegerin", "relationship_type": "causal", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation enables OPG's circulatory stability as a biomarker.", "mechanism": "High plasma OPG correlates with CAD severity and cardiovascular mortality.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation required for OPG's plasma detection.", "mechanism": "Elevated OPG predicts hospitalisation and adverse outcomes in HF.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Acute myocardial infarction (AMI)", "glycan_involvement": "Glycosylation supports OPG's stability and detection.", "mechanism": "High OPG levels predict cardiovascular death and poor prognosis in AMI.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "medium", "disease": "Arterial hypertension", "glycan_involvement": "Glycosylation required for OPG's function and measurement.", "mechanism": "High OPG levels are associated with hypertension and its complications.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation supports OPG's circulatory half-life.", "mechanism": "High plasma OPG predicts CKD risk in hypertensive patients.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation required for OPG's decoy receptor activity.", "mechanism": "OPG knockout mice show increased vascular calcification; OPG acts as a decoy receptor for RANKL.", "protein": "Osteoprotegerin", "relationship_type": "protective", "source_pmcid": "PMC11203749" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "Glycosylation required for OPG's secretion and detection.", "mechanism": "Elevated OPG levels found in patients with diabetic retinopathy.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "Glycosylation supports OPG's plasma stability.", "mechanism": "High OPG levels associated with diabetic neuropathy.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC11203749" }, { "confidence": "high", "disease": "Premature ovarian insufficiency (POI)", "glycan_involvement": "AMH is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Serum AMH levels decrease in POI and VCD-induced ovotoxicity; restoration by MFE indicates ovarian reserve.", "protein": "Anti-M\u00fcllerian hormone", "protein_enriched": { "function": "Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation", "gene_name": "afsQ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04943" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "high", "disease": "Diminished ovarian reserve", "glycan_involvement": "Glycosylation required for AMH function.", "mechanism": "AMH levels reflect follicle pool size; reduced in diminished ovarian reserve.", "protein": "Anti-M\u00fcllerian hormone", "protein_enriched": { "function": "Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation", "gene_name": "afsQ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04943" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "medium", "disease": "Premature ovarian insufficiency (POI)", "glycan_involvement": "Aromatase is glycosylated, affecting enzyme activity and estradiol synthesis.", "mechanism": "Serum estradiol decreases in POI; MFE prevents this reduction.", "protein": "Estradiol (via aromatase)", "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "medium", "disease": "Ovotoxicity", "glycan_involvement": "KITLG is glycosylated, required for receptor binding and signaling.", "mechanism": "KITLG/KIT signaling attenuates VCD-induced ovotoxicity via PI3K/Akt pathway.", "protein": "KIT ligand (KITLG)", "protein_enriched": { "function": "Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell d", "gene_name": "KITLG", "glycan_count": 3, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G23719VF", "G45395BF" ], "uniprot_id": "P21583" }, "relationship_type": "protective", "source_pmcid": "PMC11203778" }, { "confidence": "high", "disease": "Ovotoxicity", "glycan_involvement": "No direct glycosylation; upstream glycoproteins (KITLG) activate Akt.", "mechanism": "Akt activation by MFE protects ovarian cells from VCD-induced apoptosis.", "protein": "Akt (Protein Kinase B)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203778" }, { "confidence": "medium", "disease": "Ovotoxicity", "glycan_involvement": "PARP is glycosylated, which may affect stability.", "mechanism": "PARP cleavage indicates apoptosis in VCD-induced ovotoxicity; MFE prevents cleavage.", "protein": "Poly (ADP-ribose) polymerase (PARP)", "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "high", "disease": "Ovarian failure", "glycan_involvement": "Glycosylation required for AMH secretion.", "mechanism": "AMH levels decrease in ovarian failure; MFE restores levels.", "protein": "Anti-M\u00fcllerian hormone", "protein_enriched": { "function": "Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation", "gene_name": "afsQ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04943" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "medium", "disease": "Premature ovarian insufficiency (POI)", "glycan_involvement": "Glycosylation required for KITLG function.", "mechanism": "KITLG/PI3K/Akt pathway activation protects against follicle loss in POI.", "protein": "KIT ligand (KITLG)", "protein_enriched": { "function": "Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell d", "gene_name": "KITLG", "glycan_count": 3, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G23719VF", "G45395BF" ], "uniprot_id": "P21583" }, "relationship_type": "protective", "source_pmcid": "PMC11203778" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation required for AMH activity.", "mechanism": "Low AMH correlates with infertility due to reduced ovarian reserve.", "protein": "Anti-M\u00fcllerian hormone", "protein_enriched": { "function": "Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation", "gene_name": "afsQ2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04943" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "medium", "disease": "Menopause", "glycan_involvement": "Aromatase glycosylation affects estradiol synthesis.", "mechanism": "Estradiol levels drop in menopause and POI; MFE prevents reduction in VCD model.", "protein": "Estradiol (via aromatase)", "relationship_type": "biomarker", "source_pmcid": "PMC11203778" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects GP78 stability and localization.", "mechanism": "Regulates mitophagy at MAM; dysfunction impairs mitochondrial quality control.", "protein": "Glycoprotein 78 (GP78)", "protein_enriched": { "function": "Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short i", "gene_name": "AGO2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UKV8" }, "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Palmitoylation and glycosylation modulate calnexin's function.", "mechanism": "Regulates ER-phagy and Ca2+ signaling at MAM; deficiency impairs \u03b1Syn degradation.", "protein": "Calnexin", "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation regulates chaperone activity.", "mechanism": "Directly binds \u03b1Syn at MAM; involved in ER stress response and protein folding.", "protein": "BiP/GRP78", "relationship_type": "biomarker", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects immune function.", "mechanism": "Binds \u03b1Syn at MAM; initiates immune response via MHC class I presentation.", "protein": "GRP94", "relationship_type": "biomarker", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation modulates BAP31's membrane interactions.", "mechanism": "Forms MAM tether with FIS1; regulates apoptosis and neuroinflammation.", "protein": "BAP31", "protein_enriched": { "function": "Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geome", "gene_name": "TMOD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NYL9" }, "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation influences chaperone stability.", "mechanism": "Negatively correlates with \u03b1Syn accumulation; loss promotes neurodegeneration.", "protein": "Mortalin (GRP75)", "protein_enriched": { "function": "Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, th", "gene_name": "HSPA9", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G58087IP", "G07246CJ", "G49108TO" ], "uniprot_id": "P38646" }, "relationship_type": "protective", "source_pmcid": "PMC11203789" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects pump activity and localization.", "mechanism": "\u03b1Syn aggregates bind and dysregulate SERCA2b, causing Ca2+ dyshomeostasis.", "protein": "SERCA2b", "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation modulates channel function.", "mechanism": "\u03b1Syn binds VDAC1, alters mitochondrial Ca2+ signaling and energy metabolism.", "protein": "VDAC1", "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation affects tether stability.", "mechanism": "\u03b1Syn disrupts VAPB-PTPIP51 tether, impairing Ca2+ homeostasis and ATP production.", "protein": "VAPB", "protein_enriched": { "function": "Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMe", "gene_name": "VAPB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95292" }, "relationship_type": "causal", "source_pmcid": "PMC11203789" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Glycosylation modulates protein-protein interactions.", "mechanism": "Major constituents of Lewy bodies; regulate autophagy and dopamine synthesis.", "protein": "14-3-3 proteins", "relationship_type": "biomarker", "source_pmcid": "PMC11203789" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not directly addressed; DCLK1 is a putative glycoprotein.", "mechanism": "Serum DCLK1 is elevated in fibrosis; regulates stemness and inflammation via miRNA modulation.", "protein": "DCLK1", "protein_enriched": { "function": "Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system", "gene_name": "DCLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "O15075" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Not directly addressed.", "mechanism": "Serum DCLK1 is elevated in cirrhosis; promotes stemness, EMT, and inflammation.", "protein": "DCLK1", "protein_enriched": { "function": "Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system", "gene_name": "DCLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "O15075" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not directly addressed.", "mechanism": "Serum DCLK1 is elevated in HCC; drives tumor stemness and oncogenic signaling.", "protein": "DCLK1", "protein_enriched": { "function": "Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system", "gene_name": "DCLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "O15075" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b2 is a glycoprotein; glycosylation required for secretion/function.", "mechanism": "TGF-\u03b2 is upregulated in fibrosis; mediates fibrogenesis downstream of DCLK1.", "protein": "TGF-\u03b2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "TGF-\u03b2 is upregulated in cirrhosis; promotes fibrosis and pre-neoplastic changes.", "protein": "TGF-\u03b2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203803" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation status not specifically discussed.", "mechanism": "TGF-\u03b2 is not elevated in HCC; downregulation distinguishes HCC from pre-neoplastic stages.", "protein": "TGF-\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation (core fucosylation) critical for L3 isoform specificity.", "mechanism": "AFP-L3 (fucosylated isoform) is highly elevated in HCC; distinguishes HCC from cirrhosis/fibrosis.", "protein": "AFP-L3", "relationship_type": "biomarker", "source_pmcid": "PMC11203803" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation (fucosylation) involved.", "mechanism": "AFP-L3 is moderately elevated in cirrhosis; less specific than in HCC.", "protein": "AFP-L3", "relationship_type": "biomarker", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation affects stability and function.", "mechanism": "ACE2 is significantly upregulated in HCC serum; may distinguish HCC from pre-neoplastic stages.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203803" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "IL-6 is glycosylated; glycosylation required for secretion.", "mechanism": "DCLK1 promotes IL-6 release via IKK\u03b2 phosphorylation, contributing to inflammation and tumorigenesis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11203803" }, { "confidence": "high", "disease": "Type 2 diabetes/metabolic syndrome", "glycan_involvement": "Sialylated glycan headgroup mediates membrane localization and receptor interaction.", "mechanism": "Elevated GM3 with specific ceramide composition (d18:1-h24:1) downregulates insulin receptor activity and is associated with metabolic disease.", "protein": "GM3 ganglioside", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203820" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycan headgroup required for neurotrophic signaling.", "mechanism": "Deficiency of GM1 is linked to Parkinson's; GM1 supports neuronal function and survival.", "protein": "GM1 ganglioside", "relationship_type": "protective/causal", "source_pmcid": "PMC11203820" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycan headgroup interacts with amyloid-beta.", "mechanism": "Altered ceramide composition of GM1 (less d20:1 sphingosine) may facilitate amyloid-beta assembly.", "protein": "GM1 ganglioside", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11203820" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycan mediates lipoprotein interactions.", "mechanism": "Elevated GM3 in serum lipoproteins and atherosclerotic lesions in metabolic disease.", "protein": "GM3 ganglioside", "relationship_type": "biomarker", "source_pmcid": "PMC11203820" }, { "confidence": "high", "disease": "Infantile-onset symptomatic epilepsy", "glycan_involvement": "Absence of sialylated glycan disrupts neural development.", "mechanism": "Failure to synthesize GM3 leads to severe neurological symptoms.", "protein": "GM3 ganglioside", "relationship_type": "causal", "source_pmcid": "PMC11203820" }, { "confidence": "high", "disease": "Tay\u2013Sachs disease", "glycan_involvement": "Accumulation of sialylated glycan headgroup in neurons.", "mechanism": "Failure to degrade GM2 leads to neurodegeneration.", "protein": "GM2 ganglioside", "relationship_type": "causal", "source_pmcid": "PMC11203820" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Disialoganglioside glycan is tumor-specific epitope.", "mechanism": "GD2 is overexpressed on neuroblastoma cells and targeted by therapeutic antibodies (Dinutuximab).", "protein": "GD2 ganglioside", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203820" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Trisialylated glycan structure is diagnostic.", "mechanism": "GT1c with ceramide (d18:1/24:1) is a marker for glioblastoma multiforme.", "protein": "GT1c ganglioside", "relationship_type": "biomarker", "source_pmcid": "PMC11203820" }, { "confidence": "medium", "disease": "Cancer (general/metastasis)", "glycan_involvement": "Disialoganglioside glycan mediates cell signaling and immune evasion.", "mechanism": "GD3 overexpression is linked to tumor progression and metastasis.", "protein": "GD3 ganglioside", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11203820" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Indirect\u2014affects sphingolipid/glycosphingolipid balance.", "mechanism": "SphK1 increases S1P (pro-angiogenic) and decreases ceramide (anti-angiogenic); inhibition blocks tumor angiogenesis.", "protein": "Sphingosine kinase 1 (SphK1)", "protein_enriched": { "function": "Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser ex", "gene_name": "SPHK1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NYA1" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11203820" }, { "confidence": "high", "disease": "Liver dysfunction/injury", "glycan_involvement": "N-glycosylation affects ALT stability and secretion; altered glycosylation may influence biomarker levels.", "mechanism": "Elevated ALT indicates hepatocellular injury due to toxic metal exposure (notably Mn and Pb).", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "Liver dysfunction/injury", "glycan_involvement": "N-glycosylation modulates AST plasma half-life; changes may affect diagnostic accuracy.", "mechanism": "Elevated AST correlates with Pb exposure, reflecting hepatic and systemic toxicity.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "Liver dysfunction/injury", "glycan_involvement": "N-glycosylation critical for ALP membrane localization and activity; altered glycosylation may reflect disease state.", "mechanism": "ALP levels increase with Pb and Mn exposure, indicating membrane stress and cholestasis.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "Liver dysfunction/injury", "glycan_involvement": "N-glycosylation required for GGT enzymatic activity; glycan changes may modulate serum levels.", "mechanism": "GGT is elevated with Pb and Mn exposure, reduced with Hg, reflecting oxidative stress and hepatobiliary dysfunction.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "medium", "disease": "Liver dysfunction/injury", "glycan_involvement": "Albumin glycosylation affects bilirubin binding and transport; altered glycosylation may impact bilirubin metabolism.", "mechanism": "Total bilirubin increases with Se exposure, indicating impaired hepatic clearance.", "protein": "Total Bilirubin (albumin-bound)", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "N-glycosylation influences ALT secretion; glycan changes may reflect NAFLD progression.", "mechanism": "ALT elevation is a surrogate marker for NAFLD, especially with Pb and Mn exposure.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation of component proteins (ALT, GGT) affects FLI accuracy.", "mechanism": "FLI increases with Mn and Se exposure, indicating higher NAFLD risk.", "protein": "FLI (includes GGT, ALT, triglycerides)", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "N-glycosylation modulates ALP activity; altered glycosylation may signal NAFLD.", "mechanism": "ALP elevation with Pb exposure is associated with NAFLD risk.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "N-glycosylation essential for GGT function; glycan changes may reflect NAFLD.", "mechanism": "GGT is part of FLI and is elevated with Pb and Mn exposure, indicating NAFLD risk.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "N-glycosylation affects AST stability; altered glycosylation may be involved in NAFLD.", "mechanism": "AST elevation with Pb exposure is linked to NAFLD risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11203836" }, { "confidence": "high", "disease": "Congenital cytomegalovirus infection (cCMV)", "glycan_involvement": "N-glycosylation of gB is critical for proper folding and immune evasion.", "mechanism": "gB mediates viral entry and cell-to-cell spread, essential for hCMV infectivity.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "high", "disease": "Congenital cytomegalovirus infection (cCMV)", "glycan_involvement": "N-glycosylation modulates gH function and host immune recognition.", "mechanism": "gH is required for membrane fusion and viral entry into host cells.", "protein": "Human cytomegalovirus glycoprotein H (gH)", "protein_enriched": { "function": "Part of the DNA-dependent RNA polymerase which catalyzes the transcription of viral DNA into RNA using the four ribonucleoside triphosphates as substrates. Responsible for the transcription of early, ", "gene_name": "RPO132", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16716" }, "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Congenital cytomegalovirus infection (cCMV)", "glycan_involvement": "N-glycosylation affects complex stability and immune evasion.", "mechanism": "gL forms a complex with gH, facilitating viral entry.", "protein": "Human cytomegalovirus glycoprotein L (gL)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Chorioretinitis", "glycan_involvement": "Glycosylation shields gB from neutralizing antibodies, promoting persistence.", "mechanism": "gB-mediated infection of retinal cells leads to inflammation and scarring.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Retinal and choroidal scarring", "glycan_involvement": "Glycosylation modulates immune recognition and viral spread.", "mechanism": "Direct infection and immune response to gB-expressing virus cause tissue damage.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Congenital cytomegalovirus infection (cCMV)", "glycan_involvement": "Glycosylation of IgG Fc region affects effector function and half-life.", "mechanism": "CMVIG binds viral glycoproteins, neutralizing virus and reducing fetal transmission.", "protein": "CMV-specific hyperimmunoglobulin (CMVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Glycosylation aids immune evasion and persistence in neural tissues.", "mechanism": "gB-mediated infection of cochlear cells leads to inflammation and hearing loss.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "low", "disease": "Retinopathy of prematurity (ROP)", "glycan_involvement": "Glycosylation patterns influence tropism and immune response.", "mechanism": "hCMV infection in premature infants can mimic ROP via glycoprotein-mediated vascular damage.", "protein": "Human cytomegalovirus envelope glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Optic nerve atrophy", "glycan_involvement": "Glycosylation facilitates viral spread in neural tissues.", "mechanism": "Direct infection of optic nerve cells during neurogenesis leads to atrophy.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "medium", "disease": "Cerebral visual impairment (CVI)", "glycan_involvement": "Glycosylation modulates neurotropism and immune evasion.", "mechanism": "Early fetal neuroinfection by gB-expressing virus disrupts visual cortex development.", "protein": "Human cytomegalovirus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC11203846" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PRPS2 is regulated by glycosylation, affecting its activity.", "mechanism": "PRPS2 upregulation via Myc increases nucleotide synthesis, supporting cancer cell proliferation.", "protein": "PRPS2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "SLC4A7 is a membrane glycoprotein; glycosylation may affect trafficking and function.", "mechanism": "SLC4A7 upregulation by mTORC1 increases bicarbonate import, promoting nucleotide synthesis and tumor growth.", "protein": "SLC4A7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Triple Negative Breast Cancer (TNBC)", "glycan_involvement": "Not directly discussed.", "mechanism": "ADSL hyperexpression drives TNBC proliferation via mTORC1-Myc signaling and adenosine-mediated repression of MIR22HG.", "protein": "ADSL", "relationship_type": "causal", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Colorectal Carcinoma (CRC)", "glycan_involvement": "Not directly discussed.", "mechanism": "ADSL hyperexpression induces mitochondrial dysfunction, ROS accumulation, and mTORC1/c-Myc activation.", "protein": "ADSL", "relationship_type": "causal", "source_pmcid": "PMC11203890" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Not directly discussed.", "mechanism": "ADSL upregulation in glioma stem cells produces fumarate, leading to PTEN succination and PI3K/Akt/mTOR activation.", "protein": "ADSL", "relationship_type": "causal", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Not directly discussed.", "mechanism": "ATIC hyperexpression suppresses AICAR/AMPK, activating mTORC1-S6K1 and promoting HCC progression.", "protein": "ATIC", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Lung Adenocarcinoma (LUAD)", "glycan_involvement": "Not directly discussed.", "mechanism": "ATIC upregulation increases Myc and mTOR activation, enhancing LUAD cell growth and invasion.", "protein": "ATIC", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "TSC-deficient tumors", "glycan_involvement": "Not directly discussed.", "mechanism": "IMPDH inhibition selectively kills TSC-deficient tumor cells with active mTORC1 by depleting guanylate nucleotides.", "protein": "IMPDH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "medium", "disease": "Lesch-Nyhan syndrome", "glycan_involvement": "PRPS2 glycosylation may affect enzyme regulation.", "mechanism": "Deficiency of HGPRT causes PRPP accumulation, increasing purinosome frequency and altering purine metabolism.", "protein": "PRPS2", "relationship_type": "causal", "source_pmcid": "PMC11203890" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "HSP90 is a glycoprotein; glycosylation may affect chaperone function.", "mechanism": "HSP90 is essential for purinosome assembly, supporting purine synthesis and cancer cell proliferation.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203890" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "ACE is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Garlic-derived protein hydrolysate and cinnamon inhibit ACE activity, reducing angiotensin II and lowering blood pressure.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203894" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "LDL receptor glycosylation modulates ligand binding and clearance.", "mechanism": "Garlic allicin inhibits LDL uptake by macrophages, preventing atherosclerotic plaque formation.", "protein": "Low-density lipoprotein (LDL) receptor", "relationship_type": "protective", "source_pmcid": "PMC11203894" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may affect SOD secretion and stability.", "mechanism": "Garlic allicin increases SOD expression, reducing oxidative stress in cardiovascular tissues.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC11203894" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation influences CAT activity and localization.", "mechanism": "Garlic and Nigella sativa increase CAT activity, protecting against oxidative damage.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC11203894" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation affects GPX secretion and function.", "mechanism": "Garlic allicin upregulates GPX, reducing oxidative stress and apoptosis in cardiomyocytes.", "protein": "Glutathione peroxidase (GPX)", "relationship_type": "protective", "source_pmcid": "PMC11203894" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "PDGF glycosylation modulates receptor binding and signaling.", "mechanism": "Ginkgo biloba extract inhibits PDGF synthesis, reducing vascular smooth muscle proliferation and atherosclerosis risk.", "protein": "Platelet-derived growth factor (PDGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203894" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "OATP1A2 glycosylation affects membrane localization and transport activity.", "mechanism": "Green tea catechins inhibit OATP1A2, reducing intestinal absorption of antihypertensive drugs (nadolol), affecting blood pressure control.", "protein": "Organic anion-transporting polypeptide 1A2 (OATP1A2)", "relationship_type": "causal", "source_pmcid": "PMC11203894" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "P-gp glycosylation is essential for proper folding and transport function.", "mechanism": "Berberine and celery seed inhibit P-gp, altering bioavailability of antihypertensive drugs (losartan, irbesartan), impacting therapeutic efficacy.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC11203894" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "CYP3A4 glycosylation affects enzyme stability and drug metabolism.", "mechanism": "Berberine, Nigella sativa, celery, and Ginkgo biloba inhibit CYP3A4, affecting metabolism of antihypertensive drugs (losartan, amlodipine), leading to altered plasma concentrations.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "causal", "source_pmcid": "PMC11203894" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "AGEs are formed by non-enzymatic glycation of proteins, contributing to vascular pathology.", "mechanism": "Cinnamon polyphenols inhibit AGE formation, reducing endothelial damage and diabetic complications.", "protein": "Advanced glycation end products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC11203894" }, { "confidence": "high", "disease": "False biomarker results in biotin-(strept)avidin assays", "glycan_involvement": "Avidin is a glycoprotein; glycosylation affects its stability and binding.", "mechanism": "High biotin levels interfere with avidin-based immunoassays, causing false results for disease biomarkers.", "protein": "Avidin", "protein_enriched": { "function": "The biological function of avidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of avidin)", "gene_name": "AVD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G80005YU", "G81295CK" ], "uniprot_id": "P02701" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Immunodeficiency (SLC5A6-related)", "glycan_involvement": "SMVT has four N-glycosylation sites; glycosylation is important for membrane localization and function.", "mechanism": "Mutations in SLC5A6 (SMVT) impair biotin uptake, leading to defective B cell differentiation and antibody deficiency.", "protein": "SMVT", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Spontaneous gut inflammation (SMVT knockout)", "glycan_involvement": "N-glycosylation of SMVT is important for transporter function.", "mechanism": "Loss of intestinal SMVT causes biotin deficiency, leading to gut inflammation via NF-\u03baB and NLRP3 inflammasome activation.", "protein": "SMVT", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Biotinidase deficiency (BD)", "glycan_involvement": "Biotinidase is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Defective biotinidase prevents biotin recycling, causing neurological and dermatological symptoms.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Holocarboxylase synthetase deficiency (HLCS deficiency)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "HLCS mutations impair biotinylation of carboxylases, leading to metabolic and neurological symptoms.", "protein": "Holocarboxylase synthetase (HLCS)", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Biotin\u2013thiamine-responsive basal ganglia disease (BTBGD)", "glycan_involvement": "THTR2 is a glycoprotein; glycosylation may affect transporter function.", "mechanism": "SLC19A3 mutations cause thiamine transport deficiency, leading to BTBGD; biotin may upregulate SLC19A3 expression.", "protein": "Thiamine transporter-2 (THTR2/SLC19A3)", "protein_enriched": { "function": "Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism (PubMed:11731220, PubMed:33008889, PubMed:35512554, PubMed:35724964). Has no folate transport activity (PubMed:1173122", "gene_name": "SLC19A3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BZV2" }, "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Immunoglobulins are heavily glycosylated; glycosylation affects immune function.", "mechanism": "Biotin-binding immunoglobulins may contribute to autoimmunity and MS pathogenesis.", "protein": "Immunoglobulins", "relationship_type": "putative causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Alopecia", "glycan_involvement": "N-glycosylation of SMVT is important for function.", "mechanism": "SMVT deficiency impairs biotin uptake, leading to hair loss.", "protein": "SMVT", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Hearing loss (BD-related)", "glycan_involvement": "Glycosylation may affect biotinidase stability.", "mechanism": "Biotinidase deficiency causes biotin-responsive multiple carboxylase deficiency, leading to hearing loss.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Optic atrophy (BD-related)", "glycan_involvement": "Glycosylation may affect biotinidase function.", "mechanism": "Biotinidase deficiency leads to optic atrophy due to impaired biotin recycling.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC11203980" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "CRP is heavily glycosylated, affecting its stability and serum half-life.", "mechanism": "Elevated serum CRP correlates with poor survival, higher Gleason score, and increased risk of clinically significant prostate cancer.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA glycosylation patterns change in cancer, influencing detection and specificity.", "mechanism": "Higher serum PSA levels are associated with high-risk and advanced prostate cancer.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "high", "disease": "Metastatic prostate cancer", "glycan_involvement": "GlycA reflects N-acetyl glycan modifications on acute-phase glycoproteins.", "mechanism": "High plasma GlycA levels are found in patients with high-risk and metastatic prostate cancer, especially in African descendants.", "protein": "Glycoprotein acetylation (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Metastatic prostate cancer", "glycan_involvement": "Represents sialylation status of plasma glycoproteins.", "mechanism": "Elevated GlycB is associated with high inflammation and metastatic prostate cancer in African descendants.", "protein": "Acetylneuraminic acid (GlycB)", "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer recurrence", "glycan_involvement": "CD38 is glycosylated, affecting cell surface expression and function.", "mechanism": "Upregulated in African American prostate cancer, linked to immune response and recurrence risk.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates enzymatic activity and cell adhesion.", "mechanism": "Upregulated in African American prostate cancer, involved in tumor progression.", "protein": "ANPEP (Aminopeptidase N)", "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Secreted by prostate cancer-associated fibroblasts, promotes tumor growth and migration.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation affects enzymatic activity and immune modulation.", "mechanism": "Secreted by prostate cancer-associated fibroblasts, enhances cancer cell proliferation and migration.", "protein": "DPPIV (CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation influences receptor binding and angiogenic activity.", "mechanism": "Promotes angiogenesis and tumor progression; secreted by cancer-associated fibroblasts.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11203985" }, { "confidence": "medium", "disease": "Prostate cancer disparity in African descendants", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Elevated IL-6 secretion by fibroblasts in African American prostate cancer promotes inflammation and tumor progression.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11203985" }, { "confidence": "high", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "Caspase-3 is not glycosylated; glycosylation not involved.", "mechanism": "Serum caspase-3 levels are elevated in AIS patients within 24-48h of onset, reflecting neuronal apoptosis.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "Not glycosylated; glycosylation not involved.", "mechanism": "Lower caspase-3 levels in moderate/severe AIS patients are associated with early mortality, possibly indicating complete artery occlusion.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (e.g., dementia)", "glycan_involvement": "Not glycosylated; glycosylation not involved.", "mechanism": "Activation of caspase-3 induces neuronal and glial cell death, contributing to chronic neurodegeneration.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "causal", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect stability and detection.", "mechanism": "GFAP released into blood after BBB disruption in AIS; potential diagnostic marker.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "NSE is glycosylated; glycosylation may affect secretion and detection.", "mechanism": "NSE levels increase in blood after neuronal injury in AIS.", "protein": "NSE", "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "MMP-9 is glycosylated; glycosylation modulates activity and secretion.", "mechanism": "MMP-9 is upregulated in AIS, contributing to BBB breakdown and inflammation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "low", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "BNP is glycosylated; glycosylation affects stability.", "mechanism": "BNP levels may rise in AIS, reflecting cardiac stress.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-6 expression is upregulated in blood within 24h of AIS, reflecting inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates receptor binding.", "mechanism": "TNF-\u03b1 levels rise within 6h of AIS, correlating with severity and infarct extent.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Not glycosylated; glycosylation not involved.", "mechanism": "Caspase-3 upregulation observed in neurons after traumatic brain injury, indicating apoptosis.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204031" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "N-glycosylation required for GCase folding, trafficking, and activity.", "mechanism": "Biallelic GBA1 mutations cause GCase deficiency, leading to lysosomal accumulation of glucosylceramide.", "protein": "Glucocerebrosidase (GCase)", "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "high", "disease": "Action Myoclonus Renal Failure Syndrome (AMRF)", "glycan_involvement": "LIMP-2 is heavily N-glycosylated, essential for lysosomal localization.", "mechanism": "Biallelic SCARB2 mutations impair lysosomal targeting of GCase, causing AMRF.", "protein": "LIMP-2", "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "Prosaposin is glycosylated; glycosylation affects stability and lysosomal delivery.", "mechanism": "PSAP mutations cause deficiency of all saposins, including SapC, leading to GCase inactivity and GD phenotype.", "protein": "Prosaposin", "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "high", "disease": "Gaucher Disease (GD)", "glycan_involvement": "SapC is glycosylated; glycosylation may affect lysosomal function.", "mechanism": "SapC deficiency impairs GCase activation, causing GD-like symptoms.", "protein": "Saposin C (SapC)", "protein_enriched": { "function": "", "gene_name": "PSAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07602-3" }, "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "high", "disease": "Macrophage activation", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Elevated chitotriosidase activity in plasma indicates macrophage activation in GD and PSAP deficiency.", "protein": "Chitotriosidase", "relationship_type": "biomarker", "source_pmcid": "PMC11204053" }, { "confidence": "medium", "disease": "Cholesterol accumulation", "glycan_involvement": "N-glycosylation affects GCase stability and lysosomal function.", "mechanism": "GCase deficiency (via GBA1, PSAP, or SCARB2 mutations) leads to lysosomal cholesterol accumulation.", "protein": "Glucocerebrosidase (GCase)", "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "medium", "disease": "Cholesterol accumulation", "glycan_involvement": "N-glycosylation required for LIMP-2 function.", "mechanism": "LIMP-2 deficiency impairs lysosomal cholesterol efflux, leading to accumulation.", "protein": "LIMP-2", "relationship_type": "causal", "source_pmcid": "PMC11204053" }, { "confidence": "medium", "disease": "Niemann\u2013Pick C Disease (NPCD)", "glycan_involvement": "Glycosylation affects prosaposin stability and trafficking.", "mechanism": "PSAP deficiency elevates PPCS, a biomarker for NPCD, due to impaired cholesterol trafficking.", "protein": "Prosaposin", "relationship_type": "biomarker", "source_pmcid": "PMC11204053" }, { "confidence": "medium", "disease": "Cholesterol accumulation", "glycan_involvement": "Glycosylation may affect lipid binding and transport.", "mechanism": "SapA may facilitate cholesterol transport to LIMP-2, preventing accumulation.", "protein": "Saposin A", "protein_enriched": { "function": "", "gene_name": "PSAP", "glycan_count": 293, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00395TQ", "G00912UN", "G03930BU", "G04657PL", "G05049YU", "G05962QB", "G06110VR", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G09724ZC", "G10819WX", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12398HZ", "G14669DU", "G14972EH", "G15169WU", "G16125XL", "G18183SM", "G20030CU", "G20312EM", "G20528HD", "G22310AV", "G22625SJ", "G23719VF", "G25451PN", "G25637MV", "G27058EU", "G27622TD", "G27915IV", "G27947YN", "G28681TP", "G29299MO", "G29880MM", "G31852PQ", "G34989PA", "G35541EV", "G37399XV", "G37412TK", "G39619TI", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43299SD", "G43669FQ", "G43734MM", "G45359RY", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48414YA", "G53075ES", "G57317CE", "G57776ZS", "G57888GL", "G61207RZ", "G62765YT", "G62894KT", "G63889NK", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70441OD", "G70822IO", "G72291OX", "G72787SB", "G74724QE", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77582RK", "G78059CC", "G79666IR", "G79809MM", "G80075MS", "G80479JV", "G80858MF", "G80920RR", "G80966KZ", "G81198YO", "G81637OR", "G82348BZ", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84820NF", "G85269DF", "G85282JO", "G85554PZ", "G86357DX", "G86880BF", "G87123QX", "G89993FE", "G90093AU", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G95977AE", "G49108TO", "G47518TP", "G00986YT", "G01485JJ", "G02815KT", "G03216SJ", "G04483SK", "G04744XB", "G07695ZT", "G07755XJ", "G08290VR", "G11314AS", "G11994QC", "G14994KB", "G18938DW", "G20956ZV", "G22573RC", "G25079LO", "G25418HZ", "G28347RJ", "G28541PG", "G28663KH", "G29857RC", "G29905OR", "G30633FJ", "G31685JQ", "G33609NS", "G33734YD", "G34617SM", "G36191CD", "G36379GD", "G37881RL", "G39213VZ", "G39602UU", "G42264OV", "G42679AH", "G43664YB", "G45036WQ", "G45187EI", "G48584BU", "G50282JC", "G52428MJ", "G56269EA", "G56784JY", "G59924QI", "G61334IA", "G61792ET", "G64409MC", "G66937TJ", "G69411IG", "G72667IM", "G72735IY", "G77547TA", "G79286RS", "G80333GO", "G81263BG", "G81397LO", "G83006TR", "G83229XP", "G84349RE", "G85041WE", "G86182NS", "G86795LJ", "G87051GH", "G87661QW", "G88374WZ", "G89045VA", "G90575OW", "G91473PK", "G96577RX", "G57321FI", "G00406II", "G01650EU", "G02886BB", "G05724UK", "G06247RL", "G08609CW", "G10756ZZ", "G10773YW", "G13131HA", "G15664MX", "G17208MA", "G23984SE", "G27126ED", "G30521DU", "G31986NC", "G34527RW", "G36442WJ", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G51640FO", "G52890YB", "G57776ZU", "G58087IP", "G59471TH", "G59626AS", "G60834IK", "G61256FT", "G64481DJ", "G65092SV", "G70223PD", "G70888PK", "G72747WU", "G72791KH", "G78649WQ", "G80223IX", "G87389XI", "G87399DK", "G89098OM", "G90734RJ", "G92406TI", "G93500PH", "G94470IW", "G96091TT", "G98140IX", "G54612UD", "G63041LO", "G18647XP", "G29545VG", "G30248BL", "G30970QQ", "G32788FZ", "G35029YA", "G35253PZ", "G40926MX", "G44753VC", "G46524LG", "G46691LC", "G55383ZG", "G60145BJ", "G63136LV", "G67031OU", "G67164EE", "G69834CE", "G70619PT", "G83633GK", "G88891KO", "G10256JP", "G11254FL", "G14260UH", "G20425TQ", "G22355FZ", "G22768VO", "G23432EQ", "G23453IV", "G23863VK", "G25381UC", "G26145IL", "G31936TA", "G32550BI", "G49874UX", "G50045TK", "G54702KT", "G55220VL", "G61330YQ", "G61884GF", "G63628AV", "G66538GV", "G71838YU", "G72797UR", "G81295CK", "G91636VS", "G94854LT", "G96771UL" ], "uniprot_id": "P07602-1" }, "relationship_type": "protective", "source_pmcid": "PMC11204053" }, { "confidence": "medium", "disease": "Gaucher Disease (GD)", "glycan_involvement": "Glycosylation required for lysosomal localization.", "mechanism": "Acid ceramidase requires SapD for activity; PSAP deficiency impairs GlcSph generation, modifying GD biomarker levels.", "protein": "Acid ceramidase", "relationship_type": "modifier", "source_pmcid": "PMC11204053" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "IL-6 promotes autoimmunity and neuroinflammation, driving MS pathogenesis and progression.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11204061" }, { "confidence": "high", "disease": "EAE", "glycan_involvement": "Glycosylation regulates IL-6 bioactivity.", "mechanism": "IL-6 is required for EAE induction; knockout or inhibition reduces disease severity.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11204061" }, { "confidence": "high", "disease": "EAE", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "MOG acts as an autoantigen, triggering autoimmune demyelination in EAE.", "protein": "MOG", "relationship_type": "causal", "source_pmcid": "PMC11204061" }, { "confidence": "medium", "disease": "EAE", "glycan_involvement": "PD-1 is glycosylated; glycosylation modulates receptor function.", "mechanism": "Upregulation of PD-1 on T cells after IL-6 inhibition increases immunosuppression.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "protective", "source_pmcid": "PMC11204061" }, { "confidence": "medium", "disease": "EAE", "glycan_involvement": "LAG-3 glycosylation affects ligand binding.", "mechanism": "LAG-3 upregulation on CD8+ T cells after IL-6 inhibition enhances immune checkpoint-mediated suppression.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "protective", "source_pmcid": "PMC11204061" }, { "confidence": "medium", "disease": "EAE", "glycan_involvement": "TIM-3 is a mucin-domain glycoprotein; glycosylation is critical for function.", "mechanism": "TIM-3 upregulation on CD4+ and CD8+ T cells after IL-6 inhibition increases immunosuppressive signaling.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "protective", "source_pmcid": "PMC11204061" }, { "confidence": "high", "disease": "MS", "glycan_involvement": "Glycosylation may influence antibody binding and IL-6 clearance.", "mechanism": "IL-6 inhibition increases peripheral immunosuppressive response but does not improve clinical outcome in aged EAE/MS.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204061" }, { "confidence": "high", "disease": "MS", "glycan_involvement": "Glycosylation affects IL-6 detection in assays.", "mechanism": "Elevated IL-6 levels correlate with disease progression and severity in elderly MS.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204061" }, { "confidence": "medium", "disease": "MS", "glycan_involvement": "Glycosylation may affect immunogenicity and antibody recognition.", "mechanism": "Anti-MOG antibodies are used to model MS and monitor disease activity.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC11204061" }, { "confidence": "medium", "disease": "MS", "glycan_involvement": "Glycosylation status may affect therapeutic antibody interaction.", "mechanism": "Anti-IL-6 therapies may need age-specific adjustment for efficacy in progressive MS.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204061" }, { "confidence": "high", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Tyrosinase is a membrane glycoprotein; glycosylation is essential for its proper folding, stability, and trafficking.", "mechanism": "Mutations in TYR gene reduce tyrosinase activity, impairing melanin biosynthesis in ocular and cutaneous tissues.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "high", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation affects tyrosinase ER retention and activity; variant may alter glycoprotein folding and trafficking.", "mechanism": "TYR c.1205G>A (p.Arg402Gln) variant encodes a thermosensitive tyrosinase with reduced catalytic activity, leading to mild OCA.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Potential impact on glycoprotein structure and function, but not directly demonstrated.", "mechanism": "TYR c.1307G>C (p.Gly436Ala) variant (VUS) may contribute to OCA phenotype when in trans with p.Arg402Gln.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation required for tyrosinase activity; mutations may affect glycan-dependent folding and trafficking.", "mechanism": "Compound heterozygosity for TYR variants (p.Arg402Gln and p.Gly436Ala) leads to deficient melanogenic enzyme expression in retinal cells.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "high", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation status may modulate tyrosinase activity and phenotype severity.", "mechanism": "TYR c.1205G>A (p.Arg402Gln) is a risk allele for mild OCA, especially in compound heterozygotes.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204092" }, { "confidence": "high", "disease": "Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Damaging CAPN5 variants cause ADNIV via retinal inflammation and neovascularization.", "protein": "Calpain-5", "protein_enriched": { "function": "Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of ", "gene_name": "IVNS1ABP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6Y0" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV)", "glycan_involvement": "Not applicable.", "mechanism": "CAPN5 c.230A>G (p.Gln77Arg) variant is likely benign; no ADNIV phenotype observed.", "protein": "Calpain-5", "protein_enriched": { "function": "Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of ", "gene_name": "IVNS1ABP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6Y0" }, "relationship_type": "benign", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation affects tyrosinase stability and activity, indirectly influencing downstream effects.", "mechanism": "Reduced tyrosinase activity leads to lower dopamine production, which increases VEGF and angiogenesis, contributing to foveal hypoplasia.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation may affect tissue-specific expression and function.", "mechanism": "Deficient tyrosinase expression in ocular tissue leads to ocular-only hypopigmentation (mild OCA).", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "medium", "disease": "Oculocutaneous Albinism (OCA)", "glycan_involvement": "Glycosylation required for tyrosinase function in retinal development.", "mechanism": "Mutations in TYR disrupt melanin biosynthesis, leading to foveal hypoplasia and absence of foveal avascular zone.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "causal", "source_pmcid": "PMC11204092" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not directly discussed; FASN is a glycoprotein but glycosylation not specifically addressed in this study.", "mechanism": "FASN is overexpressed in breast cancer cells compared to normal cells; its expression correlates with rapid tumor progression, poor prognosis, and high risk of death.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "biomarker", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not directly discussed; glycosylation status may affect FASN function but not addressed here.", "mechanism": "Inhibition of FASN leads to reduced cell viability, induction of apoptosis, and decreased lipid droplet accumulation in breast cancer cells.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "FASN overexpression drives de novo fatty acid synthesis, supporting membrane biogenesis, energy production, and oncogenic signaling in breast cancer cells.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "causal", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "Natural compounds (e.g., Andrographis paniculata phytochemicals) inhibit FASN, reducing lipid synthesis and promoting apoptosis.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "Synthetic FASN inhibitors (e.g., orlistat) target the thioesterase domain, blocking palmitate release and inducing cancer cell death.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "Differential expression of FASN between cancer and normal cells makes it a potential diagnostic tumor marker.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "biomarker", "source_pmcid": "PMC11204123" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "FASN inhibition leads to accumulation of malonyl-CoA, energy starvation, and apoptosis in cancer cells.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "causal", "source_pmcid": "PMC11204123" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "FASN inhibition disrupts palmitate synthesis, affecting membrane architecture and oncogenic signaling.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "causal", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "FASN inhibition by AP phytochemicals blocks thioesterase domain, preventing palmitate release and lipid droplet formation.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified.", "mechanism": "Downregulation of FASN by plant extracts is associated with induction of apoptosis and cytotoxicity in breast cancer.", "protein": "Fatty acid synthase (FASN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204123" }, { "confidence": "high", "disease": "Breast cancer (benign)", "glycan_involvement": "Perforin 1 is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Downregulation in CD8+ T cells suggests impaired cytotoxic function in benign breast disease.", "protein": "Perforin 1", "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (luminal B)", "glycan_involvement": "No direct glycosylation reported for GZMA; effect likely indirect.", "mechanism": "Downregulation in CD8+ T cells indicates reduced cytotoxic potential in luminal B subtype.", "protein": "Granzyme A", "protein_enriched": { "function": "Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubM", "gene_name": "GZMA", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G37995HC", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G92275SC" ], "uniprot_id": "P12544" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (benign)", "glycan_involvement": "No direct glycosylation reported for GZMH; effect likely indirect.", "mechanism": "Downregulation in CD8+ T cells suggests impaired tumor cell killing.", "protein": "Granzyme H", "protein_enriched": { "function": "Histone demethylase that specifically demethylates both mono- and dimethylated 'Lys-9' of histone H3. May act as a transcription regulator controlling hair biology (via targeting of collagens), neural", "gene_name": "HR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43593" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (luminal B)", "glycan_involvement": "No direct glycosylation reported for GZMH; effect likely indirect.", "mechanism": "Downregulation in CD8+ T cells indicates reduced cytotoxicity in luminal B subtype.", "protein": "Granzyme H", "protein_enriched": { "function": "Histone demethylase that specifically demethylates both mono- and dimethylated 'Lys-9' of histone H3. May act as a transcription regulator controlling hair biology (via targeting of collagens), neural", "gene_name": "HR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43593" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "No direct glycosylation reported for GZMK; effect likely indirect.", "mechanism": "Upregulation in CD8+ T cells may reflect increased memory/effector T cell activity in TNBC.", "protein": "Granzyme K", "protein_enriched": { "function": "May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with ar", "gene_name": "KLK7", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49862" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (benign)", "glycan_involvement": "No direct glycosylation reported for GZMM; effect likely indirect.", "mechanism": "Downregulation in CD8+ T cells suggests impaired cytotoxic response.", "protein": "Granzyme M", "protein_enriched": { "function": "Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:11154691). However, they seem to serve as transcripti", "gene_name": "MAFG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15525" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (benign)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Downregulation in CD8+ T cells indicates altered RNA degradation and gene regulation.", "protein": "LSM2", "protein_enriched": { "function": "Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (Pub", "gene_name": "LSM4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4Z0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Breast cancer (luminal B)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Downregulation in CD8+ T cells suggests impaired RNA metabolism.", "protein": "LSM2", "protein_enriched": { "function": "Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (Pub", "gene_name": "LSM4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4Z0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Downregulation in CD8+ T cells indicates altered RNA degradation in TNBC.", "protein": "LSM2", "protein_enriched": { "function": "Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (Pub", "gene_name": "LSM4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4Z0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Downregulation in CD8+ T cells suggests impaired RNA metabolism in TNBC.", "protein": "LSM5", "protein_enriched": { "function": "Transcription activator that binds DNA elements with the consensus sequence 5'-CGGTAATTGG-3'. Binds DNA via its homeobox. Required for normal cell death of enteric neurons in the gastrointestinal trac", "gene_name": "TLX2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43763" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204132" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "PSMA is a glycoprotein; glycosylation may affect its membrane localization and ligand binding.", "mechanism": "PSMA expression in tumor cells and tumor-associated blood vessels correlates with tumor aggressiveness and proliferation (Ki67).", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204143" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Glycosylation may influence PSMA\u2019s cell surface expression and internalization.", "mechanism": "PSMA is overexpressed in TNBC, especially in tumor-associated vasculature, suggesting potential for targeted imaging and radionuclide therapy.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204143" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation is critical for PSMA\u2019s function and ligand binding.", "mechanism": "PSMA is highly overexpressed in prostate cancer cells, correlating with tumor aggressiveness, metastasis, and used for imaging and radioligand therapy.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Renal Carcinoma", "glycan_involvement": "Glycosylation affects PSMA\u2019s localization and function.", "mechanism": "PSMA is expressed in tumor-associated neovasculature, aiding in imaging and possibly therapy.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation may modulate PSMA\u2019s accessibility.", "mechanism": "PSMA detected in neovasculature, may serve as imaging target.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation may affect enzyme activity and localization.", "mechanism": "PSMA (as glutamate carboxypeptidase II) regulates glutamatergic neurotransmission; dysregulation implicated in schizophrenia.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Seizure Disorders", "glycan_involvement": "Glycosylation may impact enzymatic function.", "mechanism": "PSMA\u2019s role in NAAG hydrolysis affects glutamate signaling; dysregulation linked to seizures.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "Glycosylation may regulate PSMA\u2019s activity.", "mechanism": "Altered PSMA activity affects glutamatergic neurotransmission, implicated in Alzheimer\u2019s pathology.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Huntington\u2019s Disease", "glycan_involvement": "Glycosylation may affect PSMA\u2019s function.", "mechanism": "PSMA dysregulation impacts glutamate metabolism, contributing to Huntington\u2019s disease.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC11204143" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "Glycosylation may modulate PSMA\u2019s activity.", "mechanism": "PSMA\u2019s enzymatic activity in glutamate metabolism is implicated in ALS pathogenesis.", "protein": "Prostate-Specific Membrane Antigen (PSMA)", "relationship_type": "causal", "source_pmcid": "PMC11204143" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "GLP1R is a glycoprotein; glycosylation affects receptor function and drug binding.", "mechanism": "Activation by liraglutide promotes weight loss via appetite suppression and metabolic effects.", "protein": "GLP1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204191" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Liraglutide is a glycopeptide; glycosylation increases stability and half-life.", "mechanism": "GLP1 analog binds GLP1R, leading to weight loss and improved metabolic parameters.", "protein": "Liraglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204191" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "LDL contains glycoprotein components; glycosylation affects clearance and function.", "mechanism": "Elevated LDL is a risk factor for CVD; liraglutide reduces LDL, lowering risk.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "high", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "Glycation (not enzymatic glycosylation) of hemoglobin; used as a glycoprotein biomarker.", "mechanism": "HbA1c reflects long-term glucose control; liraglutide may reduce HbA1c.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "AST and ALT are glycoproteins; glycosylation may affect enzyme stability.", "mechanism": "FIB-4 index estimates liver fibrosis; liraglutide reduces FIB-4, indicating improved liver health.", "protein": "FIB-4 (AST, ALT, platelets)", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Elevated AST indicates liver injury; liraglutide reduces AST, suggesting improvement.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Elevated ALT indicates liver injury; liraglutide reduces ALT, suggesting improvement.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "HDL contains glycoproteins; glycosylation affects function.", "mechanism": "HDL is protective against CVD; liraglutide may modulate HDL levels.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "TGs are carried by lipoproteins with glycoprotein components.", "mechanism": "Elevated TGs are a risk factor for metabolic disease; liraglutide may reduce TGs.", "protein": "Triglycerides (TGs)", "relationship_type": "biomarker", "source_pmcid": "PMC11204191" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "GLP1R glycosylation modulates receptor signaling.", "mechanism": "GLP1R activation improves insulin sensitivity; liraglutide enhances this effect.", "protein": "GLP1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204191" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CD63 is a glycoprotein; glycosylation affects exosome targeting and stability.", "mechanism": "CD63 is enriched on exosomes from cancer cells and used for exosome identification in cancer diagnostics.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CD9 glycosylation may influence exosome-cell interactions.", "mechanism": "CD9 is a canonical exosome marker used in cancer exosome isolation and analysis.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates CD81 function in exosome biology.", "mechanism": "CD81 is a tetraspanin marker for exosomes, facilitating cancer biomarker discovery.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Selectin-ligand interactions are glycan-dependent.", "mechanism": "Selectins on EVs mediate adhesion and may facilitate metastasis.", "protein": "Selectin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Apoptotic body-related diseases (e.g., cancer, autoimmunity)", "glycan_involvement": "Annexin V is a glycoprotein; glycosylation may affect binding.", "mechanism": "Annexin V marks apoptotic bodies, which are elevated in disease states.", "protein": "Annexin V", "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Bone-related diseases", "glycan_involvement": "VEGF-A is glycosylated, affecting stability and receptor binding.", "mechanism": "Exosomal VEGF-A mRNA delivery promotes bone regeneration.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Bone-related diseases", "glycan_involvement": "BMP-2 glycosylation modulates bioactivity.", "mechanism": "Exosomal BMP-2 mRNA delivery enhances bone tissue regeneration.", "protein": "BMP-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "gp130 is glycosylated, influencing receptor function.", "mechanism": "Exosomal gp130 inhibits IL6 trans-signaling, reducing inflammation.", "protein": "IL6 signal transducer (gp130)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204223" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation patterns on CD63 may distinguish cancer-derived exosomes.", "mechanism": "Glycosylation of exosomal CD63 is studied as a diagnostic marker for prostate cancer.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "low", "disease": "Lung metastasis of osteosarcoma", "glycan_involvement": "Selectin binding is glycan-dependent.", "mechanism": "Selectin on exosomes may facilitate metastatic niche formation.", "protein": "Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC11204223" }, { "confidence": "high", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation is essential for proper folding and function of IIb/IIIa, enabling platelet aggregation.", "mechanism": "Glycoprotein IIb/IIIa inhibitors are used as a rescue strategy in PCI to prevent acute thrombotic events.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204241" }, { "confidence": "medium", "disease": "In-stent restenosis", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions on platelets.", "mechanism": "Inhibitors of IIb/IIIa reduce platelet aggregation, lowering risk of restenosis after PCI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204241" }, { "confidence": "medium", "disease": "Major adverse cardiovascular events (MACEs)", "glycan_involvement": "Glycosylation affects receptor activation and platelet function.", "mechanism": "IIb/IIIa inhibitors are used to reduce MACEs during high-risk PCI procedures.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204241" }, { "confidence": "medium", "disease": "Chronic total occlusion (CTO)", "glycan_involvement": "Glycosylation required for receptor surface expression and function.", "mechanism": "Used as rescue therapy in CTO PCI with high thrombus burden to prevent vessel closure.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204241" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation influences receptor stability and ligand binding.", "mechanism": "Targeted by inhibitors to reduce platelet aggregation in CAD interventions.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204241" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Phosphorylation and possible O-glycosylation modulate aggregation; glycosylation not detailed.", "mechanism": "Hyperphosphorylated Tau aggregates form neurofibrillary tangles, disrupting neuronal function.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Tauopathies (e.g., Pick's disease, progressive supranuclear palsy)", "glycan_involvement": "Phosphorylation and splicing; glycosylation not detailed.", "mechanism": "Abnormal Tau isoforms and aggregation drive neurodegeneration.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Creutzfeldt\u2013Jakob disease (CJD)", "glycan_involvement": "Not specified.", "mechanism": "Elevated CSF total Tau indicates rapid neuronal degeneration.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Traumatic brain injury (TBI)", "glycan_involvement": "GFAP assembly regulated by glycosylation; functional impact unclear.", "mechanism": "Astrocyte injury releases GFAP into blood/CSF; levels correlate with injury severity.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Frontotemporal lobar degeneration (FTLD)", "glycan_involvement": "GFAP glycosylation may affect filament interactions.", "mechanism": "Astrogliosis leads to elevated GFAP in CSF/blood; correlates with disease severity.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "medium", "disease": "Astrocytoma/glioblastoma", "glycan_involvement": "Isoform-specific glycosylation may affect malignancy; not detailed.", "mechanism": "GFAP isoform levels (GFAP\u03b1, GFAP\u03b4) indicate tumor differentiation and malignancy.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "O-linked glycosylation/phosphorylation sites regulate filament dynamics.", "mechanism": "Axonal damage increases NfL in CSF/blood; tracks demyelination and disease progression.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation/phosphorylation modulate NfL function.", "mechanism": "Elevated NfL reflects axonal degeneration; rises years before symptoms.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Phosphorylation/glycosylation of C-terminal tail affects axonal transport.", "mechanism": "High CSF NfL and pNfH indicate motor neuron axonal injury.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "O-glycosylation/phosphorylation regulate filament stability.", "mechanism": "Ischemic injury degrades NfL; elevated levels in CSF/blood correlate with tissue damage.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204270" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "SAA1 is not glycosylated; glycosylation not directly involved.", "mechanism": "SAA1 crosses BBB, accumulates in brain, exacerbates amyloid beta deposition, gliosis, and memory impairment; elevated in CSF and plaques.", "protein": "SAA1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11204325" }, { "confidence": "high", "disease": "Stroke (cerebral ischemia/reperfusion injury)", "glycan_involvement": "Not specified.", "mechanism": "SAA2 upregulated after stroke; knockout reduces infarct volume, neuroinflammation, and improves outcomes.", "protein": "SAA2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Not specified.", "mechanism": "SAA1 upregulated in plasma and brain post-injury; associated with neuroinflammation and BBB leakage.", "protein": "SAA1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204325" }, { "confidence": "high", "disease": "Systemic amyloidosis (AA amyloidosis)", "glycan_involvement": "Not glycosylated; glycosylation not involved.", "mechanism": "SAA1 is precursor of AA amyloid; overexpression leads to amyloid deposition in organs (rarely brain).", "protein": "SAA1", "relationship_type": "causal", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Not specified.", "mechanism": "SAA3 prevents tau hyperphosphorylation and modulates astrocyte activation via IL-10 and p38 MAPK.", "protein": "SAA3", "relationship_type": "protective", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Not specified.", "mechanism": "Chronic liver overexpression of SAA1 induces depressive-like behaviors in mice.", "protein": "SAA1", "relationship_type": "causal", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Cerebral microinfarcts/vascular injury", "glycan_involvement": "Not specified.", "mechanism": "SAA1 deposits in cerebral capillaries and microinfarcts; associated with vascular injury in hypertensive primates.", "protein": "SAA1", "relationship_type": "causal", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "SAA4 is N-glycosylated; glycosylation may affect function.", "mechanism": "SAA4 upregulated in atherosclerotic lesions; has procoagulant activity.", "protein": "SAA4", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Intracranial aneurysm", "glycan_involvement": "Not specified.", "mechanism": "SAA1 deposits in aneurysm walls; associated with wall degeneration, rupture, and inflammation.", "protein": "SAA1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204325" }, { "confidence": "medium", "disease": "Metabolic syndrome/obesity", "glycan_involvement": "Not specified.", "mechanism": "SAA1 upregulated in obesity; anti-SAA treatment prevents weight gain and insulin resistance in mice.", "protein": "SAA1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11204325" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Antibodies are glycoproteins; glycosylation affects stability and immune interactions.", "mechanism": "Antibody-conjugated liposomes (immunoliposomes) target tumor antigens for drug delivery.", "protein": "Antibody (Immunoglobulin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Folate receptor is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "Folate-conjugated liposomes target overexpressed folate receptors on tumor cells.", "protein": "Folate Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "high", "disease": "Bone Metastasis", "glycan_involvement": "Integrins are glycoproteins; glycosylation modulates ligand binding.", "mechanism": "cRGD peptide-conjugated liposomes target \u03b1v\u03b23 integrin, overexpressed in bone metastasis.", "protein": "\u03b1v\u03b23 Integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "high", "disease": "Breast Cancer (HER2+)", "glycan_involvement": "HER2 is a glycoprotein; glycosylation affects receptor function and targeting.", "mechanism": "Peptide-conjugated liposomes target HER2, overexpressed in aggressive breast cancer.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "medium", "disease": "Tumor Vasculature", "glycan_involvement": "CD13 is a glycoprotein; glycosylation may influence targeting.", "mechanism": "Peptide-conjugated liposomes target CD13, overexpressed in tumor vasculature.", "protein": "CD13", "protein_enriched": { "function": "Mediates the anchoring of the endoplasmic reticulum to microtubules", "gene_name": "CKAP4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "Q07065" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "PAK-1 is a glycoprotein; glycosylation may affect targeting.", "mechanism": "Peptide-conjugated liposomes target PAK-1, overexpressed in prostate cancer.", "protein": "p21-activated kinase 1 (PAK-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "high", "disease": "Bladder Cancer", "glycan_involvement": "PEG mimics glycan shielding, affecting immune recognition.", "mechanism": "PEGylated liposomes increase drug efficacy and reduce toxicity in bladder cancer models.", "protein": "PEG (Polyethylene Glycol) conjugated proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Fab fragments retain glycosylation sites; glycosylation affects function.", "mechanism": "Fab-conjugated liposomes improve tumor targeting and reduce immunogenicity.", "protein": "Antibody (Fab fragment)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Aptamers mimic glycan-mediated recognition.", "mechanism": "Aptamer-conjugated liposomes selectively bind tumor cell surface proteins.", "protein": "Aptamer (as glycan-mimicking ligand)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "medium", "disease": "Methicillin-resistant Staphylococcus aureus (MRSA) Infection", "glycan_involvement": "Peptide binding may interact with bacterial glycoproteins.", "mechanism": "Peptide-conjugated liposomes target bacterial surface receptors for enhanced drug delivery.", "protein": "Antibacterial peptide-conjugated liposome", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204409" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22GPI affects antigenicity and antibody binding.", "mechanism": "Anti-\u03b22GPI antibodies bind \u03b22GPI on trophoblasts, triggering tissue damage and thrombosis.", "protein": "Beta-2-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "Neonatal Lupus (NL)", "glycan_involvement": "Glycosylation modulates antigen presentation and antibody recognition.", "mechanism": "Maternal anti-Ro/SS-A IgG crosses placenta, binds fetal cardiac conduction tissue, causing inflammation and CHB.", "protein": "Ro/SS-A (Ro52/Ro60)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "Neonatal Lupus (NL)", "glycan_involvement": "Glycosylation influences immune complex formation.", "mechanism": "Maternal anti-La/SS-B IgG contributes to NL, especially with anti-Ro/SS-A co-positivity.", "protein": "La/SS-B", "relationship_type": "causal", "source_pmcid": "PMC11204490" }, { "confidence": "medium", "disease": "Congenital Heart Block (CHB)", "glycan_involvement": "Sialic acid-binding domain mediates cell-cell interactions.", "mechanism": "Upregulated SIGLEC-1 macrophages found in fetal cardiac tissue with CHB; associated with type I IFN activation.", "protein": "SIGLEC-1", "relationship_type": "biomarker", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "Neonatal Lupus (NL)", "glycan_involvement": "Fc glycosylation affects placental transfer and effector function.", "mechanism": "Maternal IgG autoantibodies cross placenta, mediating tissue-specific damage in fetus.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11204490" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "Glycosylation required for complement activation and stability.", "mechanism": "Lower increase in C3 during pregnancy correlates with higher risk of PE and adverse outcomes.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204490" }, { "confidence": "medium", "disease": "Infertility in SLE", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Anti-prothrombin antibodies elevated in SLE patients with infertility.", "protein": "Antiprothrombin", "relationship_type": "biomarker", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Antibody glycosylation modulates pathogenicity.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for APS and predicts thrombotic risk.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Antibody glycosylation influences coagulation interference.", "mechanism": "Lupus anticoagulant positivity is a high-risk marker for APS-related pregnancy complications.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC11204490" }, { "confidence": "medium", "disease": "Neonatal Lupus (NL)", "glycan_involvement": "Glycosylation may affect antigen-antibody interactions.", "mechanism": "Maternal anti-U1RNP antibodies linked to cutaneous NL in offspring.", "protein": "Anti-U1RNP antibody", "relationship_type": "causal", "source_pmcid": "PMC11204490" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation affects antibody recognition.", "mechanism": "Anti-MAG antibodies found in distal CIDP; may indicate future IgM paraproteinemia/monoclonal gammopathy.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "Neurofascin 186 is heavily glycosylated; glycosylation modulates immune recognition.", "mechanism": "Autoantibodies against neurofascin 186 found in ~10% of CIDP; disrupts nodal/paranodal architecture.", "protein": "Neurofascin 186", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "CNTN1 is glycosylated; glycan structures may influence antibody binding.", "mechanism": "Autoantibodies against CNTN1 found in nodal/paranodal CIDP; disrupts axonal conduction.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "CASPR1 glycosylation may affect immune targeting.", "mechanism": "Autoantibodies against CASPR1 found in ~10% of CIDP; affects paranodal junctions.", "protein": "Contactin-associated protein 1 (CASPR1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "GBS (AMAN/AMSAN variants)", "glycan_involvement": "GM1 is a sialylated glycosphingolipid; glycan epitope is antibody target.", "mechanism": "Anti-GM1 antibodies are diagnostic for axonal forms of GBS; mediate complement-dependent nerve injury.", "protein": "GM1 ganglioside", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "GBS (AMAN/AMSAN variants)", "glycan_involvement": "GD1a glycan structure is the antibody target.", "mechanism": "Anti-GD1a antibodies found in axonal GBS; associated with severe motor neuropathy.", "protein": "GD1a ganglioside", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "Miller\u2013Fisher syndrome (MFS)", "glycan_involvement": "GQ1b glycan epitope is the antibody target.", "mechanism": "Anti-GQ1b antibodies found in 90% of MFS; mediate ophthalmoplegia and ataxia.", "protein": "GQ1b ganglioside", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11204502" }, { "confidence": "medium", "disease": "GBS", "glycan_involvement": "MAG glycosylation may affect immune response.", "mechanism": "Elevated CSF protein (including MAG) supports diagnosis; not specific.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204502" }, { "confidence": "low", "disease": "GBS", "glycan_involvement": "Glycosylation may modulate antibody binding.", "mechanism": "Rarely, anti-neurofascin antibodies may be present in GBS; role less clear.", "protein": "Neurofascin 186", "relationship_type": "biomarker", "source_pmcid": "PMC11204502" }, { "confidence": "low", "disease": "GBS", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Autoantibodies may be present in rare GBS cases; more relevant to CIDP.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204502" }, { "confidence": "high", "disease": "Drug Hypersensitivity (DHS) to Isoniazid and Rifampin", "glycan_involvement": "HLA-A is a glycoprotein; glycosylation is essential for proper folding and antigen presentation.", "mechanism": "HLA-A*11:01 presents drug-derived peptides to T cells, increasing risk of immune-mediated hypersensitivity.", "protein": "HLA-A*11:01", "relationship_type": "biomarker", "source_pmcid": "PMC11204531" }, { "confidence": "high", "disease": "Hepatotoxicity (Drug-Induced Liver Injury)", "glycan_involvement": "HLA-DPB1 is a glycoprotein; glycosylation affects stability and antigen presentation.", "mechanism": "HLA-DPB1*05:01 increases susceptibility to immune-mediated liver injury during INH/RIF therapy.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204531" }, { "confidence": "medium", "disease": "Drug Hypersensitivity (DHS) to Isoniazid and Rifampin with Hepatotoxicity", "glycan_involvement": "Glycosylation modulates HLA-DPB1 function in immune response.", "mechanism": "Presence of HLA-DPB1*05:01 is associated with combined DHS and hepatotoxicity.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204531" }, { "confidence": "medium", "disease": "Multiple Sclerosis (Asian-type)", "glycan_involvement": "Glycosylation affects HLA-DPB1 antigen presentation.", "mechanism": "HLA-DPB1*05:01 is associated with increased risk in Asian populations.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "risk factor", "source_pmcid": "PMC11204531" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "HLA-DPB1*05:01 is linked to susceptibility in Asian populations.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "risk factor", "source_pmcid": "PMC11204531" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation impacts antigen presentation.", "mechanism": "HLA-DPB1*05:01 increases risk in Asian populations.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "risk factor", "source_pmcid": "PMC11204531" }, { "confidence": "medium", "disease": "Neuromyelitis Optica", "glycan_involvement": "Glycosylation modulates HLA-DPB1 function.", "mechanism": "HLA-DPB1*05:01 is associated with increased risk in Southern Han Chinese.", "protein": "HLA-DPB1*05:01", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DPB1", "glycan_count": 44, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05724UK", "G05962QB", "G07246CJ", "G08290VR", "G11314AS", "G11870QZ", "G14972EH", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G32788FZ", "G35541EV", "G36379GD", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G47644PP", "G51653BI", "G57776ZS", "G62765YT", "G64527OM", "G70232NH", "G70441OD", "G74724QE", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G84452RH", "G85269DF", "G86880BF", "G90659AW", "G92050GC", "G92275SC", "G93718GY", "G94854LT" ], "uniprot_id": "P04440" }, "relationship_type": "risk factor", "source_pmcid": "PMC11204531" }, { "confidence": "high", "disease": "Erythropoietic Protoporphyria (EPP)", "glycan_involvement": "Afamelanotide mimics glycoprotein hormone \u03b1-MSH, but is not itself glycosylated.", "mechanism": "Afamelanotide increases eumelanin production, improving light tolerance and quality of life in EPP patients.", "protein": "Afamelanotide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204624" }, { "confidence": "high", "disease": "X-linked Protoporphyria (XLP)", "glycan_involvement": "Acts as a glycoprotein hormone analogue.", "mechanism": "Afamelanotide increases eumelanin production, improving light tolerance and quality of life in XLP patients.", "protein": "Afamelanotide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204624" }, { "confidence": "high", "disease": "Erythropoietic Protoporphyria (EPP)", "glycan_involvement": "No direct glycosylation; relevant as a biomarker in glycoprotein hormone-regulated pathway.", "mechanism": "Elevated erythrocyte and plasma protoporphyrin levels are diagnostic and monitor disease activity.", "protein": "Protoporphyrin", "relationship_type": "biomarker", "source_pmcid": "PMC11204624" }, { "confidence": "high", "disease": "X-linked Protoporphyria (XLP)", "glycan_involvement": "No direct glycosylation.", "mechanism": "Elevated protoporphyrin levels indicate disease severity.", "protein": "Protoporphyrin", "relationship_type": "biomarker", "source_pmcid": "PMC11204624" }, { "confidence": "medium", "disease": "Erythropoietic Protoporphyria (EPP)", "glycan_involvement": "\u03b1-MSH is a glycoprotein hormone; glycosylation affects stability and receptor interaction.", "mechanism": "\u03b1-MSH pathway activation increases eumelanin, reducing phototoxicity.", "protein": "\u03b1-Melanocyte-Stimulating Hormone (\u03b1-MSH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204624" }, { "confidence": "medium", "disease": "Erythropoietic Protoporphyria (EPP)", "glycan_involvement": "Eumelanin synthesis is regulated by glycoprotein hormone signaling.", "mechanism": "Increased eumelanin protects against phototoxic skin reactions.", "protein": "Eumelanin", "relationship_type": "protective", "source_pmcid": "PMC11204624" }, { "confidence": "medium", "disease": "Protoporphyria-related Liver Disease", "glycan_involvement": "No direct glycosylation effect.", "mechanism": "Afamelanotide does not improve liver biochemistry or protoporphyrin levels.", "protein": "Afamelanotide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204624" }, { "confidence": "medium", "disease": "Protoporphyria-related Liver Disease", "glycan_involvement": "No direct glycosylation.", "mechanism": "Elevated protoporphyrin is associated with hepatic dysfunction.", "protein": "Protoporphyrin", "relationship_type": "biomarker", "source_pmcid": "PMC11204624" }, { "confidence": "high", "disease": "Erythropoietic Protoporphyria (EPP)", "glycan_involvement": "Acts via glycoprotein hormone receptor pathway.", "mechanism": "Afamelanotide increases time to phototoxic symptom onset and improves QoL.", "protein": "Afamelanotide", "relationship_type": "protective", "source_pmcid": "PMC11204624" }, { "confidence": "medium", "disease": "X-linked Protoporphyria (XLP)", "glycan_involvement": "Glycosylation modulates hormone activity.", "mechanism": "\u03b1-MSH pathway activation increases eumelanin, reducing phototoxicity.", "protein": "\u03b1-Melanocyte-Stimulating Hormone (\u03b1-MSH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204624" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CEA is a heavily glycosylated protein; glycosylation is essential for its stability and secretion.", "mechanism": "CEA is produced by CRC cells and released into circulation; elevated serum levels indicate tumor presence.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "high", "disease": "CRC recurrence", "glycan_involvement": "Glycosylation affects CEA's immunogenicity and detection by immunoassays.", "mechanism": "Elevated CEA levels are highly sensitive for detecting CRC recurrence during post-operative surveillance.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CA 19-9 is a sialylated Lewis antigen (glycan epitope) on glycoproteins and glycolipids.", "mechanism": "CA 19-9 is produced by CRC and other epithelial tumors; elevated levels may indicate tumor burden.", "protein": "Carbohydrate antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "CRC recurrence", "glycan_involvement": "Glycosylation (sialyl-Lewis a) is required for CA 19-9 antigenicity and detection.", "mechanism": "Elevated CA 19-9 levels are an independent predictor of CRC recurrence (multivariate analysis).", "protein": "Carbohydrate antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Glycosylation influences CEA's serum half-life and detection.", "mechanism": "Elevated CEA levels are associated with CRC liver metastases; PET/CT and CEA together improve detection.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Lung metastasis", "glycan_involvement": "Glycosylation is necessary for CEA's secretion and immunoreactivity.", "mechanism": "Elevated CEA levels may indicate CRC lung metastases; used in conjunction with imaging.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Chronic inflammatory bowel disease", "glycan_involvement": "Glycosylation does not distinguish malignant from benign sources.", "mechanism": "CEA may be elevated in benign inflammatory conditions, reducing specificity for CRC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC11204678" }, { "confidence": "high", "disease": "Pancreatic carcinoma", "glycan_involvement": "Sialyl-Lewis a glycan epitope is essential for CA 19-9 detection.", "mechanism": "CA 19-9 is widely used as a marker for pancreatic cancer.", "protein": "Carbohydrate antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Gastric neoplasm", "glycan_involvement": "Glycosylation (sialyl-Lewis a) is required for antigenicity.", "mechanism": "CA 19-9 may be elevated in gastric cancers.", "protein": "Carbohydrate antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC11204678" }, { "confidence": "medium", "disease": "Diverticulitis", "glycan_involvement": "Glycosylation does not distinguish malignant from benign sources.", "mechanism": "CEA may be elevated in diverticulitis, limiting its specificity for CRC.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC11204678" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation affects albumin stability and half-life.", "mechanism": "Low preoperative serum albumin predicts increased risk of AKI after surgery.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP indicates systemic inflammation, associated with higher AKI risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion and function.", "mechanism": "Abnormal PT reflects coagulation dysfunction, which can contribute to AKI.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation of coagulation factors affects their activity.", "mechanism": "Altered aPTT indicates coagulation pathway changes, linked to AKI risk.", "protein": "Activated partial thromboplastin time (aPTT) factors", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Cell surface glycoproteins mediate immune cell trafficking.", "mechanism": "Elevated WBC count reflects inflammatory response, a risk factor for AKI.", "protein": "White blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "medium", "disease": "Coagulation disorders", "glycan_involvement": "Glycosylation regulates platelet adhesion and aggregation.", "mechanism": "Platelet count and function are linked to coagulation status and AKI risk.", "protein": "Platelet surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "Elevated AST may indicate hepatic injury, which can complicate AKI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "Elevated ALT may indicate hepatic injury, which can complicate AKI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Albumin glycosylation affects bilirubin binding.", "mechanism": "Altered bilirubin levels reflect hepatic dysfunction, which may impact AKI risk.", "protein": "Total bilirubin carrier proteins (albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells.", "mechanism": "CRP is elevated in sepsis, which is a risk factor for AKI.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11204685" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Alpha-synuclein is O-GlcNAc modified, which may affect aggregation and toxicity (not directly studied here).", "mechanism": "SNCA gene triplication (3X SNCA) leads to alpha-synuclein overexpression, causing early-onset, rapidly progressive PD with dopaminergic neuron loss and Lewy body formation.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11204703" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Potential role of O-GlcNAc in modulating alpha-synuclein function; not directly addressed.", "mechanism": "Complete SNCA deletion (alpha-synuclein knockout) confers resistance to synucleinopathy and MPTP-induced neurotoxicity, but impairs dopaminergic neuron maturation.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11204703" }, { "confidence": "medium", "disease": "Lewy body disease", "glycan_involvement": "O-GlcNAc modification may reduce aggregation propensity (not directly studied here).", "mechanism": "Alpha-synuclein aggregation is the main component of Lewy bodies, a hallmark of Lewy body disease and PD.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11204703" }, { "confidence": "medium", "disease": "Multiple System Atrophy", "glycan_involvement": "Glycosylation status may influence aggregation; not directly studied.", "mechanism": "Alpha-synuclein accumulation in oligodendroglia is implicated in MSA pathogenesis.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11204703" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Modulation of glycosylation could be a therapeutic strategy; not directly tested.", "mechanism": "SNCA knock-out hiPSC-derived neurons resist synucleinopathy, suggesting therapeutic potential for SNCA targeting.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204703" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Not glycosylated; included for context.", "mechanism": "Reduced Th+ neuron expression is a marker of dopaminergic neuron loss in PD and is affected by SNCA gene dosage.", "protein": "Tyrosine hydroxylase", "protein_enriched": { "function": "Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopt", "gene_name": "TH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07101" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204703" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "O-GlcNAc modification may modulate alpha-synuclein's effect on neuron maturation.", "mechanism": "Both overexpression and absence of alpha-synuclein impair Th+ dopaminergic neuron maturation in vivo.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11204703" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect detectability and aggregation.", "mechanism": "Alpha-synuclein accumulation is a neuropathological hallmark of PD.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204703" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Not a glycoprotein; included for context.", "mechanism": "Altered subcellular localization of Lmx1a in SNCA knockout lines suggests a role in dopaminergic neuron specification affected by alpha-synuclein.", "protein": "LIM homeobox transcription factor 1 alpha (Lmx1a)", "relationship_type": "biomarker", "source_pmcid": "PMC11204703" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "O-GlcNAc modification may modulate stress response.", "mechanism": "Alpha-synuclein overexpression increases susceptibility to oxidative stress and neurotoxins, contributing to PD pathogenesis.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC11204703" }, { "confidence": "high", "disease": "Pulmonary embolism", "glycan_involvement": "Heavily glycosylated N-terminal domain; glycosylation may influence stability and detection.", "mechanism": "Elevated CA-125 at diagnosis predicts increased short-term mortality; likely reflects mesothelial activation due to inflammation, congestion, or serous effusion.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects secretion and half-life; mucin-type O-glycans predominate.", "mechanism": "CA-125 correlates with hemodynamic changes and inflammation; higher levels indicate worse prognosis.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation patterns may change in malignancy, affecting antigenicity.", "mechanism": "Widely used for diagnosis and monitoring; reflects tumor burden.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Altered glycosylation may contribute to detection.", "mechanism": "Elevated in some cases; less specific than for ovarian cancer.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "medium", "disease": "Mesothelioma", "glycan_involvement": "Glycosylation supports secretion and stability.", "mechanism": "Elevated in some patients; reflects mesothelial cell activation.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "low", "disease": "Non-Hodgkin lymphoma", "glycan_involvement": "Glycosylation may affect serum levels.", "mechanism": "Elevated in some cases; not disease-specific.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "low", "disease": "Leiomyosarcoma", "glycan_involvement": "Glycosylation may influence detection.", "mechanism": "Occasionally elevated; not specific.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation supports stability in circulation.", "mechanism": "Elevated due to serosal inflammation or effusion.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "low", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation supports secretion.", "mechanism": "Elevated in some cases, especially with pleural involvement.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation supports stability and detection.", "mechanism": "Elevated in moderate-to-severe COPD; correlates with pulmonary artery pressure.", "protein": "CA-125 (Mucin 16)", "relationship_type": "biomarker", "source_pmcid": "PMC11204777" }, { "confidence": "high", "disease": "Perioperative bleeding", "glycan_involvement": "Glycosylation is essential for fibrinogen secretion, stability, and function in clot formation.", "mechanism": "Fibrinogen supplementation restores clot formation and platelet aggregation, reducing bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204778" }, { "confidence": "high", "disease": "Hypofibrinogenaemia", "glycan_involvement": "Glycosylation required for plasma stability and detection in assays.", "mechanism": "Low plasma fibrinogen levels indicate acquired coagulopathy and bleeding risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Thromboembolic events", "glycan_involvement": "Glycosylation maintains fibrinogen solubility and prevents abnormal clot formation.", "mechanism": "Fibrinogen concentrate administration associated with reduced risk of thromboembolic events in perioperative patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "protective", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "No direct evidence in this context.", "mechanism": "No significant difference in myocardial infarction risk after fibrinogen supplementation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "neutral", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "No direct evidence in this context.", "mechanism": "No significant difference in stroke risk after fibrinogen supplementation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "neutral", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Deep venous thrombosis", "glycan_involvement": "Glycosylation affects fibrin polymerization and clot structure.", "mechanism": "No significant increase in DVT risk; trend toward reduced risk with fibrinogen concentrate.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "neutral/protective", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation affects clot dissolution and embolism risk.", "mechanism": "No significant increase in PE risk; trend toward reduced risk with fibrinogen concentrate.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "neutral/protective", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Organ dysfunction/failure", "glycan_involvement": "Glycosylation required for fibrinogen function in hemostasis.", "mechanism": "Severe bleeding and hypofibrinogenaemia can lead to tissue hypoxia and organ failure.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Hemorrhagic shock", "glycan_involvement": "Glycosylation required for plasma stability and rapid clot formation.", "mechanism": "Loss of fibrinogen during bleeding contributes to hemorrhagic shock.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11204778" }, { "confidence": "medium", "disease": "Mortality (perioperative)", "glycan_involvement": "Glycosylation required for functional fibrinogen in hemostasis.", "mechanism": "Fibrinogen supplementation may reduce mortality, but effect not statistically significant.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "protective/neutral", "source_pmcid": "PMC11204778" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "SV2A is a glycoprotein; glycosylation may affect trafficking and function.", "mechanism": "SV2A modulates neurotransmitter release; brivaracetam binds SV2A to reduce neuronal excitability.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "high", "disease": "Drug-resistant epilepsy", "glycan_involvement": "Glycosylation may influence SV2A's synaptic localization and drug binding.", "mechanism": "High-affinity binding of brivaracetam to SV2A reduces seizure frequency in drug-resistant cases.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "high", "disease": "Focal seizures", "glycan_involvement": "N-glycosylation of SV2A may regulate its stability and function.", "mechanism": "SV2A-targeting drugs (brivaracetam) decrease focal seizure incidence.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "medium", "disease": "Generalized seizures", "glycan_involvement": "Glycosylation may affect SV2A's interaction with other synaptic proteins.", "mechanism": "SV2A modulation by brivaracetam reduces generalized seizure frequency.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "medium", "disease": "Lennox-Gastaut syndrome", "glycan_involvement": "Glycosylation status may modulate therapeutic efficacy.", "mechanism": "SV2A-binding drugs are effective adjuncts in LGS therapy.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "medium", "disease": "Dravet syndrome", "glycan_involvement": "Glycosylation may influence SV2A's function in disease context.", "mechanism": "SV2A-targeting drugs may reduce seizure burden in Dravet syndrome.", "protein": "Synaptic vesicle glycoprotein 2A (SV2A)", "protein_enriched": { "function": "Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily ", "gene_name": "SV2A", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q7L0J3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204858" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "P-gp is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "P-gp overexpression leads to efflux of PARP inhibitors, causing therapy resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "PARP1 is glycosylated, but glycan role not detailed here.", "mechanism": "PARP1 overexpression is associated with DNA repair; inhibition leads to synthetic lethality in HR-deficient TNBC.", "protein": "Poly(ADP-ribose) polymerase 1 (PARP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "BRCA1 is a glycoprotein; glycosylation not discussed.", "mechanism": "BRCA1 mutations cause HR deficiency, sensitizing tumors to PARP inhibitors.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204862" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "BRCA2 is a glycoprotein; glycosylation not discussed.", "mechanism": "BRCA2 mutations cause HR deficiency, sensitizing tumors to PARP inhibitors.", "protein": "BRCA2", "protein_enriched": { "function": "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by ", "gene_name": "BRCA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G03238UC", "G37399XV", "G41247ZX", "G90382BL", "G49108TO" ], "uniprot_id": "P51587" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204862" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation modulates P-gp function.", "mechanism": "P-gp-mediated drug efflux reduces efficacy of PARP inhibitors.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "PARP1 glycosylation not discussed.", "mechanism": "High PARP1 expression in glioblastoma enables targeted imaging and therapy.", "protein": "Poly(ADP-ribose) polymerase 1 (PARP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "PARP1 glycosylation not discussed.", "mechanism": "PARP1 expression correlates with response to PARP inhibitor-based imaging and therapy.", "protein": "Poly(ADP-ribose) polymerase 1 (PARP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "PARP1 glycosylation not discussed.", "mechanism": "PARP1 upregulation in HR-deficient prostate cancer predicts response to PARP inhibitors.", "protein": "Poly(ADP-ribose) polymerase 1 (PARP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "PTEN is a glycoprotein; glycosylation not discussed.", "mechanism": "PTEN deficiency sensitizes tumors to PARP inhibitors.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204862" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates P-gp function.", "mechanism": "P-gp expression may mediate resistance to PARP inhibitors.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204862" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects MCP-1 stability and secretion.", "mechanism": "Promotes monocyte recruitment and transmigration into the intima, driving plaque formation and progression.", "protein": "MCP-1 (Monocyte Chemoattractant Protein-1)", "relationship_type": "causal", "source_pmcid": "PMC11204864" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "Glycosylation modulates MCP-1 function.", "mechanism": "Elevated in diabetic patients, reflecting increased inflammatory activity and risk for atherosclerosis.", "protein": "MCP-1 (Monocyte Chemoattractant Protein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation critical for ICAM-1 cell surface expression and function.", "mechanism": "Facilitates leukocyte adhesion and migration into atherosclerotic plaques.", "protein": "ICAM-1 (Intercellular Adhesion Molecule-1)", "relationship_type": "causal", "source_pmcid": "PMC11204864" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation influences ICAM-1 interactions with integrins.", "mechanism": "Elevated serum levels predict increased cardiovascular risk and mortality.", "protein": "ICAM-1 (Intercellular Adhesion Molecule-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ligand binding and selectin function.", "mechanism": "Higher levels in patients with atherosclerotic plaque; role in monocyte rolling and adhesion.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "medium", "disease": "Microvascular Complications in Diabetes", "glycan_involvement": "Glycosylation modulates selectin-mediated cell interactions.", "mechanism": "Elevated L-selectin associated with microvascular complications in type 2 diabetes.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation affects MCP-1 activity.", "mechanism": "High MCP-1 levels linked to plaque instability and increased CVD risk.", "protein": "MCP-1 (Monocyte Chemoattractant Protein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "high", "disease": "Diabetes Mellitus Type 2", "glycan_involvement": "N-glycosylation regulates ICAM-1 function.", "mechanism": "Diabetic patients have higher ICAM-1, reflecting endothelial activation and inflammation.", "protein": "ICAM-1 (Intercellular Adhesion Molecule-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "low", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation essential for selectin-mediated adhesion.", "mechanism": "Some studies show association with CVD risk, especially in certain populations.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204864" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect MCP-1 clearance and activity.", "mechanism": "GLP-1RA and statins reduce MCP-1 levels, potentially stabilizing plaques and lowering CVD risk.", "protein": "MCP-1 (Monocyte Chemoattractant Protein-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204864" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of \u03b22GPI affects antigenicity and immune complex formation.", "mechanism": "Autoantibodies against \u03b22GPI form complexes with ox-LDL, promoting vascular inflammation and plaque progression.", "protein": "beta2-glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP levels reflect systemic inflammation and predict cardiovascular risk in RA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204900" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased risk and progression of atherosclerosis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation regulates vWF multimerization and function.", "mechanism": "vWF promotes platelet adhesion and thrombosis in atherosclerotic plaques.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for ICAM-1 surface expression and function.", "mechanism": "ICAM-1 mediates leukocyte adhesion to endothelium, facilitating plaque inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation essential for VCAM-1 function.", "mechanism": "VCAM-1 recruits monocytes to endothelium, promoting plaque formation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycation/oxidation of LDL enhances immunogenicity and uptake.", "mechanism": "ox-LDL is taken up by macrophages, forming foam cells and driving plaque development.", "protein": "Oxidized LDL (ox-LDL)", "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Apo(a) is heavily glycosylated; glycosylation affects plasma levels and function.", "mechanism": "Lp(a) promotes macrophage activation and plaque progression.", "protein": "Lp(a)", "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect GRP78 antigenicity and cell surface expression.", "mechanism": "Autoantibodies to GRP78 activate endothelial inflammation and destabilize plaques.", "protein": "Glucose-regulated protein 78 (GRP78)", "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies to HSP60 increase endothelial activation and vascular inflammation.", "protein": "Heat shock protein 60 (HSP60)", "protein_enriched": { "function": "Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote th", "gene_name": "HSPD1", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G47702MW", "G63041LO", "G84784KF", "G85677PP", "G49108TO" ], "uniprot_id": "P10809" }, "relationship_type": "causal", "source_pmcid": "PMC11204900" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function in inflammation.", "mechanism": "Elevated CRP at discharge correlates with increased severity and mortality in type 2 diabetes patients with COVID-19.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Procalcitonin is glycosylated; glycosylation may influence its secretion and inflammatory signaling.", "mechanism": "Higher procalcitonin levels at discharge are associated with increased mortality in diabetic COVID-19 patients.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Ferritin glycosylation may affect its stability and immune signaling.", "mechanism": "Hyperferritinemia at discharge is statistically associated with severe/moderate COVID-19 and increased mortality in type 2 diabetes.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation modulates clotting and inflammation.", "mechanism": "Elevated fibrinogen at discharge is correlated with increased CRP and LDH, indicating severe inflammation in diabetic COVID-19 patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "LDH is glycosylated; glycosylation may affect enzyme stability and release during tissue damage.", "mechanism": "Higher LDH levels at discharge are associated with severe disease and increased mortality in type 2 diabetes with COVID-19.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "medium", "disease": "Anemia (in COVID-19)", "glycan_involvement": "Minor glycosylation; may influence oxidative stress response.", "mechanism": "Decreased hemoglobin at discharge correlates with severe/moderate COVID-19 and poor prognosis in type 2 diabetes.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "medium", "disease": "Hypokalemia", "glycan_involvement": "Glycosylation may affect ferritin\u2019s role in inflammation and electrolyte balance.", "mechanism": "Elevated ferritin at discharge is statistically associated with decreased serum potassium in diabetic COVID-19 patients.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "medium", "disease": "Hypokalemia", "glycan_involvement": "CRP glycosylation influences its inflammatory activity.", "mechanism": "High CRP at discharge is inversely correlated with serum potassium, indicating persistent inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "D-dimer is a glycopeptide; glycosylation affects its clearance and detection.", "mechanism": "Elevated D-dimer at discharge is associated with prothrombotic risk and severe COVID-19 in type 2 diabetes.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N-glycosylation modulates fibrinogen\u2019s function in coagulation and inflammation.", "mechanism": "Fibrinogen variants and elevated levels are associated with severe forms of COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204915" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "VEGF-A is glycosylated; glycosylation is required for dimerization and receptor binding.", "mechanism": "VEGF-A promotes angiogenesis in inflamed synovium, correlating with disease activity.", "protein": "Vascular Endothelial Growth Factor A (VEGF-A)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Integrins are glycosylated; glycosylation affects ligand binding and signaling.", "mechanism": "\u03b1v\u03b23 mediates cell adhesion, migration, and angiogenesis in RA joints.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "CD206 binds mannose/galactose glycans; glycosylation critical for ligand recognition.", "mechanism": "CD206 is upregulated on M2 macrophages in inflamed RA synovium; used for targeted imaging.", "protein": "Macrophage Mannose Receptor (CD206)", "relationship_type": "biomarker", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "MMP-9 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "MMP-9 degrades ECM, contributing to cartilage and bone destruction in RA.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates stability and receptor interaction.", "mechanism": "TNF-\u03b1 drives inflammation, angiogenesis, and joint destruction in RA.", "protein": "Tumor Necrosis Factor Alpha (TNF-\u03b1)", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC11204982" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "SSTR2A is glycosylated; glycosylation affects receptor localization and function.", "mechanism": "SSTR2A is upregulated in synovial endothelium and macrophages during RA inflammation.", "protein": "Somatostatin Receptor 2A (SSTR2A)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "CD20 is glycosylated; glycosylation may affect antibody binding.", "mechanism": "CD20 is expressed on B cells, which contribute to autoantibody production and inflammation in RA.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11204982" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "CD3 is glycosylated; glycosylation influences T cell receptor function.", "mechanism": "CD3 marks T cell infiltration in inflamed RA tissues.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC11204982" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "TSPO is glycosylated; glycosylation may affect membrane localization.", "mechanism": "TSPO is upregulated on macrophages in inflamed RA joints; used for imaging.", "protein": "Translocator Protein (TSPO)", "relationship_type": "biomarker", "source_pmcid": "PMC11204982" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Folate receptor is glycosylated; glycosylation is important for ligand binding.", "mechanism": "Folate receptor is overexpressed in activated macrophages in RA synovium.", "protein": "Folate Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC11204982" }, { "confidence": "high", "disease": "Acute Pancreatitis", "glycan_involvement": "Albumin glycosylation status may affect its antioxidant properties and stability.", "mechanism": "Low serum albumin is associated with increased mortality and complications in AP, reflecting poor nutritional and inflammatory status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "high", "disease": "All-cause Mortality in Hospitalized Patients", "glycan_involvement": "Altered glycosylation may reduce albumin's protective functions.", "mechanism": "Hypoalbuminemia is linked to higher mortality due to impaired antioxidant defense and increased inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "medium", "disease": "Acute Pancreatitis", "glycan_involvement": "Lipoprotein glycosylation can affect cholesterol transport and immune modulation.", "mechanism": "Low cholesterol levels indicate poor nutritional status and increased inflammation, correlating with higher mortality in AP.", "protein": "Total Cholesterol (LDL/HDL carriers)", "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "medium", "disease": "All-cause Mortality in Hospitalized Patients", "glycan_involvement": "Glycosylation of apolipoproteins may modulate immune response and lipid metabolism.", "mechanism": "Low cholesterol is associated with increased risk of death, reflecting malnutrition and systemic inflammation.", "protein": "Total Cholesterol (LDL/HDL carriers)", "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "high", "disease": "Acute Pancreatitis", "glycan_involvement": "Glycosylation of lymphocyte surface proteins is critical for immune cell function and trafficking.", "mechanism": "Low lymphocyte count reflects impaired immune status and is associated with higher mortality in AP.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "high", "disease": "All-cause Mortality in Hospitalized Patients", "glycan_involvement": "Altered glycosylation may impair lymphocyte activation and survival.", "mechanism": "Reduced lymphocyte count is linked to increased mortality due to compromised immunity.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11205006" }, { "confidence": "medium", "disease": "Acute Pancreatitis", "glycan_involvement": "Glycosylation may enhance albumin's antioxidant capacity.", "mechanism": "Albumin's antioxidant properties may protect against oxidative damage in AP.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC11205006" }, { "confidence": "medium", "disease": "Acute Pancreatitis", "glycan_involvement": "Defective glycosylation can reduce lymphocyte-mediated immune regulation.", "mechanism": "Impaired lymphocyte function due to low count may worsen inflammation and disease progression.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205006" }, { "confidence": "low", "disease": "Acute Pancreatitis", "glycan_involvement": "Therapeutic modulation of glycosylation could enhance albumin function.", "mechanism": "Improving albumin levels may reduce mortality risk in AP.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205006" }, { "confidence": "low", "disease": "Acute Pancreatitis", "glycan_involvement": "Targeting glycosylation pathways could boost immune response.", "mechanism": "Restoring lymphocyte count/function may improve outcomes in AP.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205006" }, { "confidence": "high", "disease": "MGUS", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects stability and function.", "mechanism": "Serum monoclonal protein is the defining biomarker for MGUS diagnosis.", "protein": "Monoclonal Immunoglobulin (M protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "high", "disease": "MGUS", "glycan_involvement": "Light chains are glycoproteins; glycosylation may affect aggregation and clearance.", "mechanism": "Abnormal FLC ratio is a risk factor for MGUS progression.", "protein": "Serum Free Light Chains (FLC)", "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Altered glycosylation could affect immunoglobulin interaction with muscle tissue.", "mechanism": "Monoclonal immunoglobulins may impact sarcomeric proteins, contributing to muscle weakness.", "protein": "Monoclonal Immunoglobulin (M protein)", "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC11205029" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation may influence FLC tissue deposition and toxicity.", "mechanism": "Lower serum FLC Lambda levels associated with low muscle function in MGUS patients.", "protein": "Serum Free Light Chains (FLC)", "relationship_type": "biomarker/causal (hypothesized)", "source_pmcid": "PMC11205029" }, { "confidence": "high", "disease": "MGUS", "glycan_involvement": "IgG glycosylation modulates immune function and disease phenotype.", "mechanism": "IgG is the most common monoclonal protein in MGUS.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "medium", "disease": "MGUS", "glycan_involvement": "IgA is heavily glycosylated; glycan structure may affect disease course.", "mechanism": "IgA MGUS is a defined subtype with distinct risk profile.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "medium", "disease": "MGUS", "glycan_involvement": "IgM glycosylation influences solubility and immune complex formation.", "mechanism": "IgM MGUS is a less common subtype.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "low", "disease": "Myopathy", "glycan_involvement": "Glycosylation may modulate immunoglobulin-muscle interactions.", "mechanism": "Monoclonal immunoglobulins may cause myopathy via interaction with muscle sarcomeric proteins.", "protein": "Monoclonal Immunoglobulin (M protein)", "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC11205029" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation status may affect immunoglobulin aggregation and pathogenicity.", "mechanism": "Higher M protein levels are associated with increased risk of progression from MGUS to multiple myeloma.", "protein": "Monoclonal Immunoglobulin (M protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may influence FLC deposition in tissues.", "mechanism": "Abnormal FLC ratio is a risk factor for progression to multiple myeloma.", "protein": "Serum Free Light Chains (FLC)", "relationship_type": "biomarker", "source_pmcid": "PMC11205029" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP indicates systemic inflammation and correlates with severe COVID-19 and poor prognosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding and receptor function.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; downregulation leads to RAAS imbalance and cardiovascular complications.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11205074" }, { "confidence": "high", "disease": "Myocardial injury", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Elevated troponin I indicates cardiac injury in severe COVID-19.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Elevated LDH reflects tissue damage and correlates with severity.", "protein": "LDH (Lactate dehydrogenase)", "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "Systemic inflammatory response", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect secretion and immune recognition.", "mechanism": "Elevated ferritin is a marker of hyperinflammation and predicts poor outcome.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Albumin is glycosylated; glycosylation affects half-life and function.", "mechanism": "Low albumin is associated with severe disease and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "high", "disease": "Thromboembolism", "glycan_involvement": "D-dimer is a glycopeptide fragment from fibrin; glycosylation affects clearance.", "mechanism": "Elevated D-dimer indicates hypercoagulability and risk of thrombotic events in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation modulates stability and detection.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and heart failure in COVID-19.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "Systemic inflammatory response", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "IL-6 drives cytokine storm, contributing to cardiac and systemic complications.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC11205074" }, { "confidence": "medium", "disease": "Systemic inflammatory response", "glycan_involvement": "TNF is glycosylated; glycosylation modulates bioactivity.", "mechanism": "TNF is a key mediator of inflammation and tissue injury in severe COVID-19.", "protein": "Tumor necrosis factor (TNF)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "Tnf", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P06804" }, "relationship_type": "causal", "source_pmcid": "PMC11205074" }, { "confidence": "high", "disease": "Chronic liver disease/cirrhosis", "glycan_involvement": "VWF glycosylation affects its multimerization and platelet adhesion.", "mechanism": "VWF levels are increased in chronic liver disease, compensating for reduced platelet count and contributing to rebalanced hemostasis.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "high", "disease": "Chronic liver disease/cirrhosis", "glycan_involvement": "Glycosylation modulates ADAMTS13 secretion and activity.", "mechanism": "Reduced ADAMTS13 in liver disease leads to increased VWF activity and platelet adhesion.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "high", "disease": "Bleeding disorders", "glycan_involvement": "N-glycosylation affects fibrinogen secretion and clot formation.", "mechanism": "Hypofibrinogenemia detected by VET is a risk factor for bleeding in trauma, obstetrics, and surgery.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Chronic liver disease/cirrhosis", "glycan_involvement": "N-glycosylation is essential for Factor VIII stability and function.", "mechanism": "Compensatory increase in Factor VIII activity in liver disease helps rebalance hemostasis.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Cardiac surgery-associated bleeding", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "Inhibition of IIb/IIIa (by abciximab) used in VET to assess platelet contribution to clot strength.", "protein": "Platelet glycoprotein IIb/IIIa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Chronic liver disease/cirrhosis", "glycan_involvement": "O-glycosylation affects thrombomodulin's anticoagulant activity.", "mechanism": "Endothelial thrombomodulin and protein C activity are compensatory mechanisms for hemostatic balance in liver disease.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Chronic liver disease/cirrhosis", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Reduced protein C activity in liver disease impairs anticoagulant pathways.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Trauma-induced coagulopathy", "glycan_involvement": "Glycosylation modulates tissue factor activity.", "mechanism": "Tissue factor exposure initiates coagulation cascade in trauma.", "protein": "Tissue factor", "relationship_type": "causal", "source_pmcid": "PMC11205135" }, { "confidence": "medium", "disease": "Bleeding disorders", "glycan_involvement": "N-glycosylation required for antithrombin secretion and function.", "mechanism": "Antithrombin deficiency increases risk of thrombosis and bleeding.", "protein": "Antithrombin", "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "low", "disease": "Recurrent pregnancy loss", "glycan_involvement": "Glycosylation affects GPIb-vWF interaction.", "mechanism": "Platelet function abnormalities detected by VET may be associated with recurrent pregnancy loss.", "protein": "Glycoprotein Ib", "relationship_type": "biomarker", "source_pmcid": "PMC11205135" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "Bacterial glycoproteins mediate adhesion and immune activation.", "mechanism": "Colonization of psoriatic skin by S. aureus induces T cell-mediated inflammatory responses via IFN-gamma.", "protein": "Staphylococcus aureus surface proteins", "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Surface glycoproteins involved in competitive exclusion.", "mechanism": "S. epidermidis inhibits S. aureus biofilm formation and may reduce pathogenic colonization.", "protein": "Staphylococcus epidermidis surface proteins", "relationship_type": "protective", "source_pmcid": "PMC11205136" }, { "confidence": "high", "disease": "Guttate psoriasis", "glycan_involvement": "M protein is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "Molecular mimicry between M protein and keratin 14 triggers T cell activation and psoriatic lesions after streptococcal infection.", "protein": "Streptococcal M protein", "protein_enriched": { "function": "Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the ", "gene_name": "spa", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02976" }, "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Guttate psoriasis", "glycan_involvement": "Potential glycosylation may influence antigenicity.", "mechanism": "Autoimmune response against K14 due to cross-reactivity with streptococcal M protein.", "protein": "Keratin 14 (K14)", "protein_enriched": { "function": "The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filam", "gene_name": "KRT14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02533" }, "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "LL-37 is a glycoprotein; glycosylation may modulate immune recognition.", "mechanism": "LL-37 acts as an autoantigen, activating dendritic cells and T cells, promoting inflammation.", "protein": "LL-37 (cathelicidin antimicrobial peptide)", "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Surface glycoproteins mediate competitive exclusion.", "mechanism": "C. acnes restricts colonization by methicillin-resistant S. aureus, maintaining skin homeostasis.", "protein": "Cutibacterium acnes surface proteins", "relationship_type": "protective", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Fungal glycoproteins may act as antigens.", "mechanism": "Malassezia triggers new psoriatic plaques; improvement seen with antifungal therapy.", "protein": "Malassezia ovalis cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "medium", "disease": "Atopic dermatitis", "glycan_involvement": "Glycoproteins mediate adhesion and immune evasion.", "mechanism": "S. aureus colonization exacerbates skin inflammation.", "protein": "Staphylococcus aureus surface proteins", "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "low", "disease": "Leishmania major infection", "glycan_involvement": "Surface glycoproteins involved in immune modulation.", "mechanism": "S. epidermidis induces T cell-mediated protection against L. major.", "protein": "Staphylococcus epidermidis surface proteins", "relationship_type": "protective", "source_pmcid": "PMC11205136" }, { "confidence": "low", "disease": "Rosacea", "glycan_involvement": "Glycoproteins mediate immune activation.", "mechanism": "S. aureus colonization may contribute to chronic inflammation.", "protein": "Staphylococcus aureus surface proteins", "relationship_type": "causal", "source_pmcid": "PMC11205136" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "N-glycosylation critical for MHC class II stability and peptide binding", "mechanism": "Genetic predisposition via antigen presentation to autoreactive T cells", "protein": "HLA-DR3", "relationship_type": "causal", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "N-glycosylation affects peptide loading and immune recognition", "mechanism": "Genetic risk via altered antigen presentation", "protein": "HLA-DQ2", "relationship_type": "causal", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "N-glycosylation impacts MHC class II function", "mechanism": "Allele increases susceptibility by modulating immune response", "protein": "HLA-DQB1*02:01", "relationship_type": "causal", "source_pmcid": "PMC11205248" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "N-glycosylation modulates MHC class II surface expression", "mechanism": "Allele reduces risk by influencing antigen presentation", "protein": "HLA-DPB1*04:01", "relationship_type": "protective", "source_pmcid": "PMC11205248" }, { "confidence": "medium", "disease": "Hashimoto Thyroiditis", "glycan_involvement": "N-glycosylation affects immune tolerance", "mechanism": "Absence correlates with increased anti-thyroid antibodies", "protein": "HLA-DPB1*04:01", "relationship_type": "protective", "source_pmcid": "PMC11205248" }, { "confidence": "medium", "disease": "Vitamin D Deficiency", "glycan_involvement": "N-glycosylation may affect immune regulation and vitamin D metabolism", "mechanism": "Allele associated with lower serum vitamin D levels", "protein": "HLA-DPB1*03:01", "relationship_type": "biomarker", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Celiac Disease", "glycan_involvement": "N-glycosylation influences antigen presentation to T cells", "mechanism": "Haplotype strongly associated with anti-transglutaminase antibodies", "protein": "HLA-DRB1*04:01-DQA1*03-DQB1*03:01", "relationship_type": "causal", "source_pmcid": "PMC11205248" }, { "confidence": "medium", "disease": "Celiac Disease", "glycan_involvement": "N-glycosylation affects MHC class I function", "mechanism": "Allele correlates with anti-transglutaminase antibody positivity", "protein": "HLA-C03:03", "relationship_type": "biomarker", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Hashimoto Thyroiditis", "glycan_involvement": "Glycosylation affects antibody stability and immune complex formation", "mechanism": "Presence indicates thyroid autoimmunity", "protein": "Anti-thyroid peroxidase antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Celiac Disease", "glycan_involvement": "Glycosylation modulates antibody-antigen interactions", "mechanism": "Presence indicates celiac autoimmunity", "protein": "Anti-transglutaminase antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11205248" }, { "confidence": "high", "disease": "Ascariasis", "glycan_involvement": "IgE glycosylation affects stability and immune recognition.", "mechanism": "Elevated IgE indicates immune response to Ascaris infection.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker", "source_pmcid": "PMC11205314" }, { "confidence": "high", "disease": "Ascariasis", "glycan_involvement": "IgG4 glycosylation modulates antibody function and detection.", "mechanism": "Anti-Ascaris IgG4 is a sensitive and specific marker for diagnosis.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Biliary ascariasis", "glycan_involvement": "Glycosylation essential for alpha-1-antitrypsin function.", "mechanism": "Alpha-1-antitrypsin deficiency ruled out as cause of biliary symptoms.", "protein": "Alpha-1-antitrypsin", "relationship_type": "differential diagnosis", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Biliary ascariasis", "glycan_involvement": "Glycosylation influences secretin stability and activity.", "mechanism": "Secretin secretion decreases sphincter of Oddi tone, facilitating parasite migration.", "protein": "Secretin", "protein_enriched": { "function": "Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:25332973). Exerts its biological effects by binding to secretin", "gene_name": "SCT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09683" }, "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Biliary ascariasis", "glycan_involvement": "Glycosylation affects hormone-receptor interaction.", "mechanism": "Cholecystokinin secretion decreases sphincter of Oddi tone, aiding parasite entry into bile ducts.", "protein": "Cholecystokinin", "protein_enriched": { "function": "This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release fr", "gene_name": "CCK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P06307" }, "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "high", "disease": "Eosinophilia", "glycan_involvement": "IgE glycosylation modulates effector cell binding.", "mechanism": "Elevated IgE promotes eosinophil activation in response to helminth infection.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "high", "disease": "Biliary ascariasis", "glycan_involvement": "Glycosylation impacts antibody detection and function.", "mechanism": "Presence of anti-Ascaris IgG4 supports diagnosis of biliary ascariasis.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Cholangitis", "glycan_involvement": "Glycosylation affects IgE-mediated cell activation.", "mechanism": "IgE-mediated immune response contributes to biliary inflammation.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Cholecystitis", "glycan_involvement": "Glycosylation modulates IgE function.", "mechanism": "IgE elevation associated with allergic and inflammatory response in gallbladder.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation influences IgE stability and effector functions.", "mechanism": "IgE elevation reflects immune activation during pancreatic inflammation due to parasite migration.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "causal", "source_pmcid": "PMC11205314" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects enzyme stability and localization.", "mechanism": "Inhibition of acetylcholinesterase increases acetylcholine levels, improving cognitive symptoms.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP trafficking and cleavage.", "mechanism": "APP processing leads to amyloid-beta accumulation, a hallmark of AD.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC11205363" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may affect tau aggregation and stability.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to neurodegeneration.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC11205363" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "N-glycosylation influences enzyme activity and drug response.", "mechanism": "Cholinesterase inhibitors target acetylcholinesterase to improve cognition in MCI.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "medium", "disease": "Cognitive dysfunction", "glycan_involvement": "N-glycosylation regulates transporter surface expression.", "mechanism": "Choline uptake is essential for acetylcholine synthesis; dysfunction impairs cognition.", "protein": "Choline transporter (SLC5A7)", "protein_enriched": { "function": "Participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integri", "gene_name": "TDRKH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2W6" }, "relationship_type": "causal", "source_pmcid": "PMC11205363" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates receptor function and trafficking.", "mechanism": "NMDA receptor antagonists (memantine) reduce excitotoxicity in AD.", "protein": "NMDA receptor (GRIN1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation affects enzyme activity.", "mechanism": "Cholinesterase inhibitors may improve cognitive symptoms in Parkinson's.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "low", "disease": "Cerebral Small Vessel Disease", "glycan_involvement": "N-glycosylation impacts enzyme function.", "mechanism": "Cholinergic precursors improve cognition in vascular brain injury.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "low", "disease": "Vascular dementia", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "Cholinesterase inhibitors may slow cognitive decline in vascular dementia.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205363" }, { "confidence": "low", "disease": "Apathy", "glycan_involvement": "N-glycosylation may influence therapeutic efficacy.", "mechanism": "Cholinergic therapy reduces apathy symptoms in AD and MCI.", "protein": "Acetylcholinesterase", "relationship_type": "protective", "source_pmcid": "PMC11205363" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "N-glycosylation affects APOE stability and function in lipid transport.", "mechanism": "APOE gene polymorphisms (especially \u03b54 allele) increase risk for T2DM by affecting lipid metabolism and insulin sensitivity.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Ischemic Heart Disease (IHD)", "glycan_involvement": "Glycosylation modulates APOE interaction with lipoprotein receptors, influencing atherogenesis.", "mechanism": "APOE \u03b54/4 and \u03b53/4 genotypes are associated with increased risk of IHD in T2DM patients via dyslipidemia and atherosclerosis.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "N-glycosylation may affect APOE-mediated clearance of lipoproteins from circulation.", "mechanism": "APOE \u03b53/4 and \u03b52/3 genotypes are more frequent in diabetics with stroke, suggesting increased susceptibility via vascular lipid accumulation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation influences APOE's lipid-binding and receptor interactions.", "mechanism": "APOE polymorphisms (especially \u03b54/4) lead to elevated TC, TG, LDL, VLDL and decreased HDL, driving dyslipidemia.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates APOE's receptor binding and lipid transport.", "mechanism": "APOE \u03b54 allele impairs lipid clearance, promoting LDL accumulation and atherosclerotic plaque formation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC11205396" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect APOE's vascular interactions.", "mechanism": "APOE polymorphisms are associated with higher prevalence of hypertension in T2DM, possibly via effects on vascular lipid deposition.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Ischemic Heart Disease (IHD)", "glycan_involvement": "N-glycosylation status may influence APOE's biomarker utility.", "mechanism": "APOE genotype 4/4 is most frequently found in diabetics with IHD, serving as a genetic biomarker for risk stratification.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation may modulate APOE's role in cerebrovascular risk.", "mechanism": "APOE genotypes 3/4 and 2/3 are most frequent in diabetics with stroke, indicating genetic susceptibility.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11205396" }, { "confidence": "medium", "disease": "Ischemic Heart Disease (IHD)", "glycan_involvement": "Glycosylation may enhance protective APOE isoform function.", "mechanism": "APOE genotype 2/2 is considered cardioprotective, associated with lower risk of IHD.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation affects APOE's lipid transport efficiency.", "mechanism": "APOE genotype distribution correlates with lipid profile abnormalities in T2DM patients.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11205396" }, { "confidence": "high", "disease": "Schistosomiasis", "glycan_involvement": "Multiple N- and O-glycosylation sites contribute to protein stability and function.", "mechanism": "Smserpin-p46 inhibits host neutrophil serine proteases, aiding parasite immune evasion and survival.", "protein": "Smserpin-p46", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205507" }, { "confidence": "medium", "disease": "Schistosomiasis", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Host immune responses to Smserpin-p46 are associated with resistance to schistosomiasis.", "protein": "Smserpin-p46", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11205507" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates inhibitory activity.", "mechanism": "Smserpin-p46 inhibits neutrophil cathepsin G and elastase, reducing NETosis and inflammation.", "protein": "Smserpin-p46", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11205507" }, { "confidence": "medium", "disease": "Schistosomiasis", "glycan_involvement": "Not discussed.", "mechanism": "Cathepsin G mediates NETosis, contributing to parasite killing; inhibited by Smserpin-p46.", "protein": "Cathepsin G", "protein_enriched": { "function": "Serine protease with trypsin- and chymotrypsin-like specificity (PubMed:29652924, PubMed:8194606). Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of ", "gene_name": "CTSG", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G31852PQ", "G41247ZX", "G47644PP", "G88891KO", "G49108TO" ], "uniprot_id": "P08311" }, "relationship_type": "causal", "source_pmcid": "PMC11205507" }, { "confidence": "medium", "disease": "Schistosomiasis", "glycan_involvement": "Not discussed.", "mechanism": "Elastase mediates NETosis and larvicidal activity; inhibited by Smserpin-p46.", "protein": "Elastase", "protein_enriched": { "function": "Cleaves host elastin, collagen, IgG, and several complement components as well as endogenous pro-aminopeptidase (PubMed:11533066). Autocatalyses processing of its pro-peptide (PubMed:1744034, PubMed:9", "gene_name": "lasB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14756" }, "relationship_type": "causal", "source_pmcid": "PMC11205507" }, { "confidence": "medium", "disease": "Schistosomiasis", "glycan_involvement": "Glycosylation may influence detection sensitivity.", "mechanism": "Stage-specific expression and tegument localization make Smserpin-p46 a candidate diagnostic marker.", "protein": "Smserpin-p46", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205507" }, { "confidence": "medium", "disease": "Schistosomiasis", "glycan_involvement": "Glycosylation may affect vaccine efficacy.", "mechanism": "Potential vaccine antigen due to immunogenicity and role in immune evasion.", "protein": "Smserpin-p46", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205507" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "PTX3 is a glycoprotein; glycosylation affects stability and function.", "mechanism": "PTX3 is produced locally in atherosclerotic lesions, correlates with local inflammation and plaque vulnerability.", "protein": "Pentraxin 3", "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation modulates PTX3's interaction with immune cells.", "mechanism": "Serum PTX3 levels correlate with adverse outcomes and plaque vulnerability in CAD.", "protein": "Pentraxin 3", "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "MMP-9 is glycosylated, which affects secretion and activity.", "mechanism": "MMP-9 degrades extracellular matrix, promoting plaque instability and rupture.", "protein": "Matrix metalloproteinase-9", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Acute cardiovascular events", "glycan_involvement": "Glycosylation influences MMP-9's proteolytic function.", "mechanism": "Elevated serum MMP-9 predicts risk of plaque rupture and acute events.", "protein": "Matrix metalloproteinase-9", "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Apo(a) component is heavily glycosylated, affecting plasma levels and pathogenicity.", "mechanism": "Lp(a) promotes inflammation, increases adhesion molecule expression, and is linked to plaque instability.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Acute cardiovascular events", "glycan_involvement": "Glycosylation of apo(a) modulates its clearance and function.", "mechanism": "High Lp(a) levels predict acute events even in statin-treated patients.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "medium", "disease": "Acute cardiovascular events", "glycan_involvement": "Copeptin is a glycopeptide; glycosylation may affect stability.", "mechanism": "Copeptin is released in response to stress and is a marker for acute events.", "protein": "Copeptin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Plaque instability/vulnerability", "glycan_involvement": "Glycosylation influences PTX3's local inflammatory role.", "mechanism": "PTX3 levels correlate with plaque vulnerability assessed by imaging.", "protein": "Pentraxin 3", "relationship_type": "biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Plaque instability/vulnerability", "glycan_involvement": "Glycosylation of apo(a) tail influences pathogenicity.", "mechanism": "Lp(a) contributes to prothrombotic and antifibrinolytic effects, increasing plaque vulnerability.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Plaque instability/vulnerability", "glycan_involvement": "Glycosylation modulates MMP-9 secretion and activity.", "mechanism": "MMP-9 activity leads to extracellular matrix breakdown, increasing risk of plaque rupture.", "protein": "Matrix metalloproteinase-9", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11205508" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Insulin is glycosylated, affecting stability and receptor binding.", "mechanism": "Insulin levels and resistance are central to T2DM pathophysiology.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205547" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation modulates receptor function and cell surface expression.", "mechanism": "Defective insulin receptor signaling leads to insulin resistance.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC11205547" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects SGLT-2 trafficking and function.", "mechanism": "SGLT-2 inhibitors (e.g., canagliflozin) lower blood glucose by blocking renal glucose reabsorption.", "protein": "SGLT-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205547" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "PPAR-\u03b3 activity modulates glycoprotein expression involved in insulin signaling.", "mechanism": "Activation by pioglitazone improves insulin sensitivity in adipose, liver, and muscle.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205547" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation regulates GLUT4 trafficking and membrane localization.", "mechanism": "GLUT4 translocation is impaired in insulin resistance, reducing glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC11205547" }, { "confidence": "medium", "disease": "Diabetic dyslipidemia", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Reduced HDL-C is characteristic of diabetic dyslipidemia.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC11205547" }, { "confidence": "medium", "disease": "Diabetic dyslipidemia", "glycan_involvement": "TG metabolism is regulated by glycoprotein enzymes (e.g., lipoprotein lipase).", "mechanism": "Elevated TG is a hallmark of diabetic dyslipidemia.", "protein": "TG", "relationship_type": "biomarker", "source_pmcid": "PMC11205547" }, { "confidence": "medium", "disease": "Hyperuricemia", "glycan_involvement": "UA transporters are glycoproteins; glycosylation affects renal handling.", "mechanism": "UA levels are linked to insulin resistance and metabolic syndrome.", "protein": "UA", "relationship_type": "biomarker", "source_pmcid": "PMC11205547" }, { "confidence": "low", "disease": "Beta-cell dysfunction", "glycan_involvement": "GAD is glycosylated, influencing immunogenicity.", "mechanism": "GAD antibodies are used to exclude T1DM; GAD is involved in beta-cell function.", "protein": "GAD", "relationship_type": "biomarker", "source_pmcid": "PMC11205547" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Modulates glycoprotein expression in lipid metabolism.", "mechanism": "Pioglitazone improves lipid profiles and insulin sensitivity, reducing cardiovascular risk.", "protein": "Pioglitazone target proteins", "relationship_type": "protective", "source_pmcid": "PMC11205547" }, { "confidence": "high", "disease": "Carotid Artery Stenosis (CAS)", "glycan_involvement": "CD163 is a heavily glycosylated scavenger receptor; glycosylation affects its stability and function.", "mechanism": "Elevated plasma CD163 reflects increased macrophage activation and plaque vulnerability.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "high", "disease": "Major Adverse Cardiovascular Events (MACE)", "glycan_involvement": "Glycosylation modulates CD163 shedding and plasma levels.", "mechanism": "High plasma CD163 predicts increased risk of MACE in CAS patients.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences receptor-ligand interactions in plaque macrophages.", "mechanism": "CD163+ macrophages promote intraplaque hemorrhage and plaque progression.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "causal", "source_pmcid": "PMC11205582" }, { "confidence": "high", "disease": "Carotid Artery Stenosis (CAS)", "glycan_involvement": "IL-6 is glycosylated, which affects its secretion and receptor binding.", "mechanism": "Elevated plasma IL-6 indicates increased inflammation and plaque instability.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "high", "disease": "Major Adverse Cardiovascular Events (MACE)", "glycan_involvement": "Glycosylation modulates IL-6 stability and bioactivity.", "mechanism": "High plasma IL-6 predicts increased risk of MACE in CAS patients.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects IL-6 receptor interactions and downstream signaling.", "mechanism": "IL-6 promotes endothelial dysfunction and monocyte recruitment, driving plaque formation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation impacts CD163 shedding and detection in plasma.", "mechanism": "Elevated CD163 is associated with symptomatic carotid plaques and increased stroke risk.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation influences IL-6 plasma half-life.", "mechanism": "High IL-6 levels correlate with increased risk of stroke in CAS patients.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation regulates CD163 function and plasma levels.", "mechanism": "Elevated CD163 predicts higher risk of myocardial infarction in CAS.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation affects IL-6 activity and detection.", "mechanism": "High IL-6 levels are associated with increased risk of myocardial infarction in CAS.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205582" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Insulin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated fasting insulin and HOMA-IR indicate insulin resistance and T2DM progression.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glucagon is glycosylated; glycosylation may affect secretion.", "mechanism": "Altered glucagon-to-insulin ratio is associated with T2DM and metabolic syndrome.", "protein": "Glucagon", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "Gcg", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55095" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Adiponectin is heavily glycosylated; glycosylation is critical for multimerization and function.", "mechanism": "Higher adiponectin levels are protective against NAFLD; BCG increases adiponectin.", "protein": "Adiponectin (high-molecular-weight)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLUT1 is N-glycosylated; glycosylation affects trafficking and function.", "mechanism": "BCG increases glucose uptake in monocytes, improving glucose metabolism in T2DM.", "protein": "Monocyte glucose transporter (GLUT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation patterns may influence immune recognition.", "mechanism": "Autoimmune attack on beta-cell glycoproteins leads to T1DM.", "protein": "Pancreatic islet beta-cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "CD25 is glycosylated; glycosylation modulates immune function.", "mechanism": "BCG induces regulatory T cells, suppressing autoimmunity in T1DM.", "protein": "Regulatory T cell surface glycoproteins (e.g., CD25)", "relationship_type": "protective", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Glucose Intolerance", "glycan_involvement": "Surface glycoproteins mediate immune cell function and trafficking.", "mechanism": "BCG-induced trained immunity in bone marrow cells protects against glucose intolerance.", "protein": "Bone marrow cell surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11205624" }, { "confidence": "low", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect serum stability.", "mechanism": "ALT elevation indicates liver injury in NAFLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Bacterial glycoproteins are key for immunogenicity.", "mechanism": "BCG glycoproteins stimulate immune response, conferring protection.", "protein": "BCG cell wall glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205624" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation essential for function.", "mechanism": "Increased adiponectin improves metabolic parameters; BCG may enhance adiponectin.", "protein": "Adiponectin (high-molecular-weight)", "relationship_type": "protective", "source_pmcid": "PMC11205624" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "gp120 is heavily glycosylated; glycan shield mediates cell interactions", "mechanism": "gp120 activates hepatic stellate cells, promoting inflammation and fibrogenesis", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "N-glycans on gp120 critical for receptor binding and immune evasion", "mechanism": "gp120 mediates viral entry into host cells via CD4 and coreceptors", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "high", "disease": "HBV infection", "glycan_involvement": "HBsAg is glycosylated, affecting secretion and immune recognition", "mechanism": "HBsAg presence indicates active HBV infection", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Procollagen is N-glycosylated, required for proper folding and secretion", "mechanism": "Upregulated in hepatocytes by HIV interaction, leading to ECM deposition", "protein": "Alpha-1 procollagen", "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b21 is glycosylated, affecting secretion and activity", "mechanism": "TGF-\u03b21 upregulated in response to HIV, promotes fibrogenesis", "protein": "Transforming growth factor beta-1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CXCR4 is N-glycosylated, influencing ligand binding", "mechanism": "HIV binds CXCR4 on hepatocytes, promoting fibrogenic signaling", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CCR5 is N-glycosylated, modulating receptor function", "mechanism": "HIV binds CCR5 on hepatocytes, induces alpha-1 procollagen production", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "HIV-HBV co-infection", "glycan_involvement": "Glycosylation modulates immune recognition and cell tropism", "mechanism": "gp120-mediated immune activation exacerbates liver injury in co-infection", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects HBsAg secretion and immune evasion", "mechanism": "Chronic HBV infection (marked by HBsAg) drives immune-mediated liver injury and fibrosis", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation required for TGF-\u03b21 maturation and function", "mechanism": "Chronic upregulation leads to advanced fibrosis and cirrhosis", "protein": "Transforming growth factor beta-1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11205675" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Elevated cTnI indicates myocardial injury in COVID-19 patients and predicts adverse outcomes.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "high", "disease": "Acute Myocardial Injury", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Elevated cTnI is the defining marker of acute myocardial injury.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Patients with heart failure are more likely to have elevated cTnI during COVID-19, indicating worse prognosis.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Atrial fibrillation is associated with higher cTnI and increased risk of myocardial injury in COVID-19.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "CKD is associated with increased risk of myocardial injury and elevated cTnI in COVID-19.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Obesity is associated with higher risk of myocardial injury and elevated cTnI in COVID-19.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "Arterial Hypertension", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Hypertension is associated with increased risk of myocardial injury and elevated cTnI in COVID-19.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation may affect viral binding, but not discussed in detail here.", "mechanism": "SARS-CoV-2 binds to ACE2 on cardiac cells, leading to direct cardiac injury.", "protein": "Angiotensin-Converting Enzyme 2 (ACE2)", "protein_enriched": { "function": "Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis (P", "gene_name": "ACE2", "glycan_count": 349, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G03644CB", "G04657PL", "G05049YU", "G06247RL", "G07246CJ", "G07755XJ", "G07799LX", "G08293MJ", "G08918WF", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10846ZT", "G12341GU", "G12580WI", "G13131HA", "G14972EH", "G15038BD", "G15486FH", "G16175ZV", "G19379ID", "G19464WF", "G19517GM", "G20528HD", "G20956ZV", "G22768VO", "G25079LO", "G25451PN", "G25987BV", "G27058EU", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G29651HS", "G30740WO", "G31852PQ", "G32788FZ", "G35029YA", "G35541EV", "G36670VW", "G37399XV", "G37412TK", "G39446WN", "G39471UU", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G42466VF", "G43223CG", "G43669FQ", "G44211QA", "G44753VC", "G44953PJ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G49284IH", "G49755GI", "G49955PK", "G50073PQ", "G54600FO", "G55132BD", "G55382TU", "G56518TU", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59937CP", "G60033FS", "G60834IK", "G60923RB", "G62765YT", "G62792OG", "G65184UU", "G67324HN", "G68318VE", "G68490OW", "G69364JQ", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G72791KH", "G75568BH", "G76295SF", "G79666IR", "G80075MS", "G80475RE", "G80669SJ", "G80735OA", "G80920RR", "G81124ET", "G82364UA", "G82443XX", "G83460ZZ", "G83555HU", "G83646BJ", "G85144OK", "G85282JO", "G85740DB", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G88725PI", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G95177YH", "G95835XS", "G43417UB", "G75365RL", "G94583DZ", "G93579XB", "G98896IU", "G32926LW", "G41126SR", "G43638QT", "G54417MJ", "G61751GZ", "G98596OT", "G29068FM", "G23729WG", "G87384DY", "G27391WQ", "G58001LT", "G10756ZZ", "G23505EP", "G79941IJ", "G80728XN", "G81315DD", "G00273SJ", "G01485JJ", "G02528FI", "G10773YW", "G10819WX", "G11314AS", "G16125XL", "G23719VF", "G24528MX", "G27915IV", "G29905OR", "G30970QQ", "G37509XX", "G37995HC", "G43769HG", "G47644PP", "G49739MP", "G49906RN", "G59924QI", "G63041LO", "G72747WU", "G73686WG", "G77547TA", "G80479JV", "G85269DF", "G85554PZ", "G95865ZB", "G98611JV", "G40926MX", "G48414YA", "G55220VL", "G68008QO", "G81006GJ", "G01160VV", "G05962QB", "G06969ZX", "G22573RC", "G27947YN", "G34989PA", "G37818NZ", "G60967DT", "G70888PK", "G91208VE", "G93718GY", "G00031MO", "G00033MO", "G00420UH", "G01457KB", "G01614ZM", "G02030ZB", "G03127AL", "G03382KH", "G04791QM", "G05642HQ", "G05724UK", "G06110VR", "G06356OH", "G07410AW", "G07483YN", "G08146BT", "G10256JP", "G10691MJ", "G11041DA", "G11457RF", "G11629QQ", "G11637WL", "G11870QZ", "G14994KB", "G15169WU", "G16828VN", "G20732FY", "G21507RO", "G22140GZ", "G22310AV", "G22355FZ", "G23432EQ", "G23863VK", "G24835MQ", "G24954UD", "G25481DT", "G25637MV", "G26403SG", "G27251WT", "G28052FT", "G28106CM", "G29880MM", "G29931IJ", "G30159WR", "G31153XO", "G31596VW", "G31916IQ", "G32550BI", "G33609NS", "G34617SM", "G34838RM", "G37442IW", "G37868ZX", "G37881RL", "G39018CC", "G39188ZX", "G39213VZ", "G39595FH", "G39943KJ", "G41611UP", "G42358LZ", "G43694RQ", "G44215PV", "G45359RY", "G45495MK", "G46687AB", "G46831QF", "G47518TP", "G49108TO", "G49299ZV", "G49644CL", "G49874UX", "G50045TK", "G50757KG", "G51640FO", "G52527GH", "G52934AK", "G55484MX", "G56102PZ", "G56749GV", "G56903ZB", "G57818FI", "G57888GL", "G58667NI", "G59126YU", "G59456VR", "G59536GA", "G60070LT", "G60145BJ", "G60605ZN", "G60890ZT", "G62461SM", "G63628AV", "G64394MX", "G64527OM", "G64973KT", "G66676MI", "G66760KM", "G66937TJ", "G68209WQ", "G68698AP", "G72667IM", "G72735IY", "G72797UR", "G74430RZ", "G74722FL", "G74724QE", "G75594YZ", "G75798PH", "G75983OB", "G76163CP", "G78059CC", "G79568CQ", "G80223IX", "G80393PG", "G80858MF", "G80966KZ", "G81263BG", "G81295CK", "G82119TF", "G82252QI", "G82348BZ", "G82942ZJ", "G83204BU", "G83295QG", "G83892WB", "G83945MQ", "G84452RH", "G84467IZ", "G84820NF", "G85542KD", "G85608AG", "G87015RU", "G87618BG", "G88417ED", "G89098OM", "G89319AW", "G90093AU", "G90789YQ", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G91875JA", "G92684AL", "G93656SY", "G93994MR", "G94435QH", "G94854LT", "G97876DH", "G99074EO", "G99342HD", "G99858XP", "G99966GV", "G99969SS" ], "uniprot_id": "Q9BYF1" }, "relationship_type": "causal", "source_pmcid": "PMC11205688" }, { "confidence": "high", "disease": "In-hospital Mortality (COVID-19)", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Elevated cTnI on admission predicts higher risk of in-hospital mortality in COVID-19 patients.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "high", "disease": "Need for Invasive Mechanical Ventilation (COVID-19)", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "Elevated cTnI is associated with increased risk of requiring invasive mechanical ventilation.", "protein": "Cardiac Troponin I", "protein_enriched": { "function": "Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity", "gene_name": "TNNI3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19429" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205688" }, { "confidence": "high", "disease": "Lobular inflammation", "glycan_involvement": "IL-10 is a glycoprotein; glycosylation is required for secretion and stability, but specific glycan changes not discussed.", "mechanism": "IL-10 exerts anti-inflammatory effects; decreased IL-10 levels are associated with increased lobular inflammation in morbidly obese patients.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11205754" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "IL-10 glycosylation is necessary for function; no disease-specific glycan changes described.", "mechanism": "Loss of IL-10-mediated anti-inflammatory action may contribute to progression from lobular inflammation to NASH.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11205754" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "General glycoprotein function; no specific glycan modification discussed.", "mechanism": "Lower IL-10 levels correlate with increased severity of NAFLD and its inflammatory progression.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11205754" }, { "confidence": "medium", "disease": "Simple steatosis", "glycan_involvement": "IL-10 glycosylation required for secretion; no steatosis-specific glycan changes described.", "mechanism": "IL-10 serum levels decrease as steatosis grade increases, indicating anti-inflammatory protection is lost.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11205754" }, { "confidence": "low", "disease": "Fibrosis", "glycan_involvement": "IL-10 glycosylation required for function; no fibrosis-specific glycan changes described.", "mechanism": "Animal models suggest IL-10 loss leads to fibrosis; human data limited in this study.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC11205754" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "General glycoprotein function; no cirrhosis-specific glycan changes described.", "mechanism": "Progressive loss of IL-10 may contribute to cirrhosis development via unchecked inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC11205754" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "General glycoprotein function; no HCC-specific glycan changes described.", "mechanism": "IL-10 protective role inferred from progression of NAFLD/NASH to HCC; not directly studied here.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC11205754" }, { "confidence": "high", "disease": "Lobular inflammation", "glycan_involvement": "IL-10 glycosylation required for detection in serum assays.", "mechanism": "IL-10 serum and hepatic levels decrease with increasing lobular inflammation, suggesting utility as a biomarker.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205754" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "IL-10 glycosylation required for stability and detection.", "mechanism": "IL-10 levels may serve as an early biomarker for NASH risk before liver enzyme changes.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205754" }, { "confidence": "medium", "disease": "Lobular inflammation", "glycan_involvement": "Therapeutic IL-10 requires proper glycosylation for efficacy.", "mechanism": "Restoring IL-10 or its signaling may counteract lobular inflammation and prevent NASH progression.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205754" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for proper cell surface localization and receptor interaction.", "mechanism": "CD200 may interact with SARS-CoV-2 SP1, modulating immune suppression via the CD200:CD200R pathway.", "protein": "CD200 (OX-2 membrane glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205781" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "SP1 mediates viral entry and immune evasion; highly conserved BmP domain is essential for host recognition.", "protein": "SARS-CoV-2 Spike protein (SP1)", "relationship_type": "causal", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "CD200R1 interaction with CD200 suppresses immune responses; antagonists may restore antiviral immunity.", "protein": "CD200R1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for receptor activity.", "mechanism": "CD200R2 engagement by CD200 or viral mimics modulates dendritic cell function and Treg development, aiding immune evasion.", "protein": "CD200R2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Integrin glycosylation modulates ligand binding and signaling.", "mechanism": "Spike protein interacts with integrins, affecting cell adhesion, fusion, and inflammatory signaling.", "protein": "Alpha integrins (e.g., \u03b1v\u03b23, \u03b1v\u03b26, \u03b15\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Heparan sulfate glycosylation is critical for spike binding.", "mechanism": "Syndecan-4 binds spike glycoprotein, promoting cellular entry and transmission, especially for Delta variant.", "protein": "Syndecan-4", "protein_enriched": { "function": "Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413)", "gene_name": "SDC4", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "P31431" }, "relationship_type": "causal", "source_pmcid": "PMC11205781" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike binding affinity.", "mechanism": "ACE2 is the main entry receptor for SARS-CoV-2 via spike protein binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11205781" }, { "confidence": "high", "disease": "Chronic viral infection", "glycan_involvement": "Glycosylation required for immune modulation.", "mechanism": "vCD200 mimics host CD200, suppressing immune responses and promoting viral persistence (e.g., herpesviruses, CMV).", "protein": "Viral CD200 (vCD200)", "relationship_type": "causal", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Peptide itself is not glycosylated but targets glycoprotein interaction.", "mechanism": "Acts as CD200R antagonist, inhibiting CD200/CD200R interaction and potentially alleviating immune suppression.", "protein": "Peptide VTWQKKKAVSPANM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205781" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune recognition.", "mechanism": "Conserved glycoprotein domain used for universal vaccine design.", "protein": "Hemagglutinin (Influenza A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205781" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune evasion", "mechanism": "gp120 mediates viral entry by binding to CD4 on host cells", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC11205825" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "N-glycosylation affects gp120 binding and immune recognition", "mechanism": "CD4 is the primary receptor for HIV entry", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation status affects antigenicity", "mechanism": "p24 antigen is used for early HIV diagnosis", "protein": "HIV p24 (Gag)", "relationship_type": "biomarker", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Glycosylation may affect drug binding", "mechanism": "Targeted by NNRTIs/NRTIs; mutations confer resistance", "protein": "HIV reverse transcriptase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of host proteins may be altered by PI therapy", "mechanism": "Protease inhibitors disrupt lipid metabolism", "protein": "HIV protease", "relationship_type": "causal", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability and serum levels", "mechanism": "Elevated ALT indicates ART-induced liver injury", "protein": "ALT (alanine transaminase)", "relationship_type": "biomarker", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability and serum levels", "mechanism": "Elevated AST indicates ART-induced liver injury", "protein": "AST (aspartate transaminase)", "relationship_type": "biomarker", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Glycosylation may affect drug binding", "mechanism": "Targeted by INSTIs; mutations confer resistance", "protein": "HIV integrase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "AIDS", "glycan_involvement": "Glycosylation modulates cell-cell interactions", "mechanism": "CD8+ T cell counts reflect immune status in HIV/AIDS", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205825" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation shields fusion domains", "mechanism": "gp41 mediates fusion of viral and host membranes", "protein": "HIV envelope glycoprotein gp41", "relationship_type": "causal", "source_pmcid": "PMC11205825" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "CRP levels rise in response to systemic inflammation and infection, reflecting severity of sepsis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Procalcitonin is glycosylated; glycosylation may affect its serum half-life.", "mechanism": "Procalcitonin increases during bacterial infection and sepsis, used to monitor response to therapy.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Albumin glycosylation status can change during inflammation, affecting function.", "mechanism": "Serum albumin decreases in sepsis due to capillary leakage and inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Altered Fc glycosylation modulates immune effector functions.", "mechanism": "IgG glycosylation patterns are altered in RA, contributing to disease pathogenesis.", "protein": "Immunoglobulin G", "relationship_type": "causal", "source_pmcid": "PMC11205918" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Transferrin glycosylation affects iron binding and transport.", "mechanism": "Transferrin levels reflect iron status and are altered in chronic anemia.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "high", "disease": "Periprosthetic joint infection", "glycan_involvement": "Glycosylation influences CRP's interaction with immune cells.", "mechanism": "CRP is elevated in response to joint infection and used to monitor treatment response.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "medium", "disease": "Multidrug-resistant bacterial infection", "glycan_involvement": "Glycosylation may affect detection sensitivity in assays.", "mechanism": "Procalcitonin is used to detect and monitor severe bacterial infections, including resistant strains.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11205918" }, { "confidence": "high", "disease": "Lower respiratory tract infection (LRTI)", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and function.", "mechanism": "CRP levels rise in response to inflammation during LRTI in cancer patients.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Mortality (death)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased mortality in cancer patients with LRTI.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation and immune interactions.", "mechanism": "Low platelet count (thrombocytopenia) is associated with increased mortality in cancer patients with LRTI.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Lymphopenia", "glycan_involvement": "Glycosylation affects lymphocyte trafficking and immune function.", "mechanism": "Lymphopenia is linked to poor outcomes and higher mortality in cancer patients with LRTI.", "protein": "Lymphocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11205937" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Glycosylation modulates neutrophil adhesion and migration.", "mechanism": "Neutrophilia is prevalent in solid tumor patients with LRTI, indicating inflammation.", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Lower respiratory tract infection (LRTI)", "glycan_involvement": "Bacterial glycoproteins mediate host cell adhesion and immune evasion.", "mechanism": "S. aureus infection is a major cause of LRTI in cancer patients.", "protein": "Staphylococcus aureus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Lower respiratory tract infection (LRTI)", "glycan_involvement": "Capsular polysaccharides and glycoproteins aid in immune evasion.", "mechanism": "K. pneumoniae is a frequent pathogen in LRTI among cancer patients.", "protein": "Klebsiella pneumoniae surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205937" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Major surface glycoprotein is heavily glycosylated, mediating host interaction.", "mechanism": "P. jirovecii causes pneumonia in immunocompromised cancer patients.", "protein": "Pneumocystis jirovecii glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205937" }, { "confidence": "medium", "disease": "Lower respiratory tract infection (LRTI)", "glycan_involvement": "Cell wall glycoproteins mediate adhesion and immune modulation.", "mechanism": "C. albicans can cause fungal LRTI in cancer patients.", "protein": "Candida albicans glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11205937" }, { "confidence": "medium", "disease": "Lower respiratory tract infection (LRTI)", "glycan_involvement": "Hemagglutinin glycosylation affects viral entry and immune recognition.", "mechanism": "Influenza virus infection detected in cancer patients with LRTI.", "protein": "Influenza virus hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11205937" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "Glycosylation required for NSP4 function and host cell interaction.", "mechanism": "NSP4 glycoprotein acts as an enterotoxin, inducing diarrhea via cell signaling and chloride secretion.", "protein": "NSP4 enterotoxin", "protein_enriched": { "function": "Methyltransferase: Displays a capping enzyme activity. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enz", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P33424" }, "relationship_type": "causal", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Rotavirus diarrhea", "glycan_involvement": "Glycosylation mediates host cell binding and immune signaling.", "mechanism": "Bifidobacterium S-layer glycoproteins mediate adhesion to host cells and may block viral entry.", "protein": "Surface layer glycoprotein (S-layer)", "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "Glycosylation critical for viral infectivity and host cell recognition.", "mechanism": "VP4/VP7 glycoproteins facilitate rotavirus entry into enterocytes.", "protein": "VP4/VP7 (rotavirus surface glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Shigella infection", "glycan_involvement": "Glycosylation enables mucus binding and competitive exclusion.", "mechanism": "SpaCBA pili glycoproteins compete for mucus binding sites, reducing pathogen adhesion.", "protein": "SpaCBA pili (L. rhamnosus GG)", "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "No glycosylation; direct peptide action.", "mechanism": "Peptide produced by B. infantis IM1 inhibits rotavirus replication.", "protein": "11-mer peptide (MHQPHQPLPPT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Salmonella infection", "glycan_involvement": "Glycosylation facilitates host cell interaction.", "mechanism": "S-layer glycoproteins mediate probiotic adhesion, displacing Salmonella from enterocytes.", "protein": "Surface layer glycoprotein (S-layer)", "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Cronobacter sakazakii infection", "glycan_involvement": "Glycosylation mediates competitive exclusion.", "mechanism": "Probiotic S-layer glycoproteins block pathogen adhesion to enterocytes.", "protein": "Surface layer glycoprotein (S-layer)", "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Salmonella infection", "glycan_involvement": "Pig-MAP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Pig-MAP levels decrease with probiotic intervention, indicating reduced inflammation.", "protein": "Pig major acute-phase protein (Pig-MAP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206103" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "IgA glycosylation critical for mucosal immunity.", "mechanism": "IgA in breast milk protects infants from rotavirus infection.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "Clostridium difficile-associated diarrhea", "glycan_involvement": "Glycosylation mediates host interaction and antimicrobial activity.", "mechanism": "Bifidobacterium S-layer glycoproteins inhibit C. difficile growth via competitive exclusion and antimicrobial production.", "protein": "Surface layer glycoprotein (S-layer)", "relationship_type": "protective", "source_pmcid": "PMC11206103" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike protein binding affinity.", "mechanism": "Hesperidin may block SARS-CoV-2 entry by interfering with ACE2 receptor binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike protein N-glycans are critical for host cell interaction.", "mechanism": "Hesperidin may inhibit spike-mediated viral entry and replication.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206107" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-6 is glycosylated, affecting stability and secretion.", "mechanism": "Hesperidin reduces IL-6 levels, mitigating cytokine storm.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CRP glycosylation modulates immune function.", "mechanism": "Hesperidin lowers CRP, indicating reduced inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206107" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "VCAM-1 glycosylation regulates cell adhesion.", "mechanism": "Hesperidin decreases VCAM-1, reducing vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TNF-\u03b1 glycosylation affects receptor binding.", "mechanism": "Hesperidin reduces TNF-\u03b1, dampening inflammatory response.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "GLUT4 glycosylation influences membrane trafficking.", "mechanism": "Hesperidin promotes GLUT4 translocation, improving glucose uptake.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "apoB glycosylation affects lipoprotein assembly.", "mechanism": "Hesperidin reduces apoB expression, improving lipid profile.", "protein": "apoB", "relationship_type": "biomarker", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "VEGF glycosylation modulates receptor interaction.", "mechanism": "Hesperidin inhibits VEGF, suppressing tumor angiogenesis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206107" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Sialidase acts on glycan substrates for viral release.", "mechanism": "Glucosyl hesperidin inhibits sialidase, blocking influenza replication.", "protein": "Sialidase (neuraminidase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206107" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "MP is a glycoprotein; glycosylation status may affect detection and disease progression.", "mechanism": "MP concentration in serum/urine reflects tumor burden and is used for diagnosis and monitoring.", "protein": "Monoclonal Immunoglobulin (MP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Monoclonal Gammopathies (MGs)", "glycan_involvement": "Glycosylation may influence MP properties and detection.", "mechanism": "MP serves as a biomarker for diagnosis and monitoring of MGs.", "protein": "Monoclonal Immunoglobulin (MP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "medium", "disease": "MGUS", "glycan_involvement": "Glycosylation of light chains is associated with increased progression risk.", "mechanism": "Light chain glycosylation detected by MS is a risk factor for progression in MGUS.", "protein": "Immunoglobulin Light Chain", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Light Chain Amyloidosis", "glycan_involvement": "Presence of glycosylation is indicative of disease.", "mechanism": "Light chain glycosylation detected by MS points to diagnosis of amyloidosis.", "protein": "Immunoglobulin Light Chain", "relationship_type": "diagnostic indicator", "source_pmcid": "PMC11206176" }, { "confidence": "medium", "disease": "Cold Agglutinin Disease", "glycan_involvement": "Glycosylation is a marker for disease presence.", "mechanism": "Light chain glycosylation detected by MS suggests cold agglutinin disease.", "protein": "Immunoglobulin Light Chain", "relationship_type": "diagnostic indicator", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation affects antibody structure and detection.", "mechanism": "Used in MM treatment; may interfere with endogenous MP detection.", "protein": "Therapeutic Monoclonal Antibody (IgG kappa)", "relationship_type": "therapeutic agent", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Minimal Residual Disease (MRD) in MM", "glycan_involvement": "Glycosylation may affect sensitivity of detection.", "mechanism": "Detection of MP by MS in serum is used for MRD assessment.", "protein": "Monoclonal Immunoglobulin (MP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation status is linked to disease progression.", "mechanism": "Light chain glycosylation detected by MS provides additional risk stratification.", "protein": "Immunoglobulin Light Chain", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "medium", "disease": "Non-secretory Multiple Myeloma", "glycan_involvement": "Glycosylation may influence detectability.", "mechanism": "MS enables detection of MP in patients previously categorized as non-secretors.", "protein": "Monoclonal Immunoglobulin (MP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Monoclonal Gammopathies (MGs)", "glycan_involvement": "Glycosylation differences aid in distinguishing therapeutic from endogenous antibodies.", "mechanism": "Therapeutic antibodies can interfere with MP detection; MS can distinguish them.", "protein": "Therapeutic Monoclonal Antibody (IgG kappa)", "relationship_type": "interference", "source_pmcid": "PMC11206176" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation isomerization (detected by WFA lectin) is essential for its biomarker function.", "mechanism": "M2BPGi is secreted by hepatic stellate cells and reflects fibrogenesis; levels correlate with fibrosis stage.", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation detected by WFA is critical for disease association.", "mechanism": "Elevated M2BPGi levels predict advanced fibrosis and cirrhosis; high levels after therapy indicate risk for hepatocarcinoma.", "protein": "Mac-2 binding protein glycosylation isomer (M2BPGi)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation is required for secretion and stability.", "mechanism": "CHI3L1 promotes ECM remodeling; serum levels correlate with fibrosis stage and outperform other markers.", "protein": "Chitinase 3-like protein 1 (CHI3L1/YKL-40)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation affects secretion and detection in serum.", "mechanism": "GP73 is upregulated in damaged hepatocytes; serum levels are elevated in cirrhosis and predict poor outcomes.", "protein": "Golgi protein 73 (GP73)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "HA is a glycosaminoglycan; its structure is essential for function.", "mechanism": "HA accumulates due to increased synthesis and decreased degradation in fibrosis; serum levels reflect ECM turnover.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect stability and clearance.", "mechanism": "PIIINP is released during collagen synthesis; serum levels correlate with fibrosis stage.", "protein": "N-terminal propeptide of procollagen type III (PIIINP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation is important for function and detection.", "mechanism": "Laminin is a basement membrane glycoprotein; serum levels increase with fibrosis.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects secretion and ECM integration.", "mechanism": "Type IV collagen is deposited in fibrotic liver; serum levels correlate with fibrosis stage.", "protein": "Type IV collagen", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "TIMP-1 inhibits MMPs, promoting ECM accumulation; serum levels predict fibrosis.", "protein": "Tissue inhibitor of metalloproteinase-1 (TIMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "WFA lectin binds specific glycan structures on M2BP.", "mechanism": "WFA+-M2BP reflects altered glycosylation in fibrosis; used in clinical assays.", "protein": "Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206202" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Increased sialylation on glycoproteins at cell surface.", "mechanism": "Hypersialylation promotes tumor cell invasion, migration, and immune evasion.", "protein": "Sialoglycans (cell surface sialylated glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Tumor metastasis", "glycan_involvement": "Terminal sialic acids on glycoproteins mediate interactions.", "mechanism": "Sialylation enhances metastatic potential by facilitating immune escape and cell motility.", "protein": "Sialoglycans (cell surface sialylated glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Sialylated glycoproteins bind Siglec receptors.", "mechanism": "Sialoglycans recruit Siglec-7/9 on NK cells, inhibiting cytotoxicity.", "protein": "Sialoglycans (cell surface sialylated glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Recognition of sialylated glycoproteins.", "mechanism": "Siglec-7 binding to sialoglycans suppresses NK cell-mediated tumor killing.", "protein": "Siglec-7", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl ", "gene_name": "SIGLEC7", "glycan_count": 33, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G55220VL", "G05724UK", "G06110VR", "G06356OH", "G06656BE", "G08606CV", "G21196UL", "G22140GZ", "G22310AV", "G23863VK", "G27102CT", "G29880MM", "G39188ZX", "G39943KJ", "G46687AB", "G48414YA", "G49108TO", "G49874UX", "G50045TK", "G57141NR", "G57818FI", "G67030CA", "G72797UR", "G73455AR", "G75727PF", "G80155BS", "G80858MF", "G81295CK", "G84452RH", "G90093AU", "G90206GU", "G98068RN", "G98205FV" ], "uniprot_id": "Q9Y286" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Recognition of sialylated glycoproteins.", "mechanism": "Siglec-9 binding to sialoglycans suppresses NK cell-mediated tumor killing.", "protein": "Siglec-9", "protein_enriched": { "function": "Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by c", "gene_name": "SIGLEC9", "glycan_count": 5, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G59626AS", "G95865ZB", "G62765YT", "G11101UV", "G56770VP" ], "uniprot_id": "Q9Y336" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206204" }, { "confidence": "medium", "disease": "Immune evasion", "glycan_involvement": "Sialic acid modification of Fas receptor.", "mechanism": "Sialylation inhibits Fas receptor internalization, preventing apoptosis.", "protein": "Fas receptor (CD95)", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Sialylation of integrin glycoproteins.", "mechanism": "Sialylation inhibits integrin-mediated adhesion, promoting invasion.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Breast cancer (HER2+)", "glycan_involvement": "Removal of sialic acids from HER2 glycoprotein.", "mechanism": "Antibody\u2013sialidase conjugates desialylate HER2+ tumors, enhancing NK cell killing.", "protein": "HER2 (human epidermal growth factor receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Kidney dysfunction", "glycan_involvement": "Loss of sialic acids from podocyte glycoproteins.", "mechanism": "PFN-induced desialylation impairs glomerular filtration, causing nephropathy.", "protein": "Podocyte sialoglycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Immune checkpoint resistance", "glycan_involvement": "Sialylation modulates immune cell recognition.", "mechanism": "Sialylated glycans act as immune checkpoints; inhibition enhances immunotherapy.", "protein": "Sialoglycans (cell surface sialylated glycoproteins)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206204" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Insulin is glycosylated, affecting its stability and clearance.", "mechanism": "Insulin levels reflect glycemic control and insulin resistance.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycation (non-enzymatic glycosylation) of hemoglobin.", "mechanism": "HbA1c indicates long-term glycemic control.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "GGT is glycosylated, influencing its secretion and activity.", "mechanism": "Elevated GGT is a marker of liver injury.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "AST glycosylation affects its serum levels.", "mechanism": "AST elevation signals hepatocellular damage.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALT glycosylation modulates its activity.", "mechanism": "ALT elevation is indicative of liver cell injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALP glycosylation affects its isoform distribution.", "mechanism": "ALP is elevated in cholestatic liver disease.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycosylation influences receptor binding and clearance.", "mechanism": "Elevated LDL-c promotes plaque formation.", "protein": "Low-density lipoprotein cholesterol (LDL-c)", "relationship_type": "causal", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties.", "mechanism": "HDL-c facilitates reverse cholesterol transport.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "VLDL glycosylation affects lipid transport.", "mechanism": "Elevated VLDL-c is associated with metabolic syndrome.", "protein": "Very-low-density lipoprotein cholesterol (VLDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "TG transport is mediated by glycosylated lipoproteins.", "mechanism": "High TG levels increase cardiovascular risk.", "protein": "Triglycerides (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC11206266" }, { "confidence": "high", "disease": "Atherosclerotic Coronary Heart Disease (CAD)", "glycan_involvement": "SREBP1 is glycosylated, affecting stability and activity.", "mechanism": "Regulates lipid synthesis; JZGX downregulates SREBP1 to reduce hepatic lipid accumulation and atherosclerosis.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Atherosclerotic Coronary Heart Disease (CAD)", "glycan_involvement": "Glycosylation modulates FASN activity and localization.", "mechanism": "Catalyzes fatty acid synthesis; JZGX downregulates FASN, decreasing lipid synthesis and plaque formation.", "protein": "FASN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects PTGS2 stability and secretion.", "mechanism": "Mediates pro-inflammatory prostanoid synthesis; JZGX downregulates PTGS2, reducing vascular inflammation.", "protein": "PTGS2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206304" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation influences CYP3A folding and activity.", "mechanism": "Involved in cholesterol and lipid metabolism; JZGX upregulates CYP3A, improving lipid homeostasis.", "protein": "CYP3A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Atherosclerotic Coronary Heart Disease (CAD)", "glycan_involvement": "Glycosylation may affect receptor localization and ligand binding.", "mechanism": "Promotes fatty acid \u03b2-oxidation; JZGX activates PPAR\u03b1, reducing lipid accumulation and inflammation.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Atherosclerotic Coronary Heart Disease (CAD)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Regulates lipid uptake and efflux; JZGX activates PPAR\u03b3, promoting reverse cholesterol transport and plaque reduction.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Pro-inflammatory cytokine elevated in CAD; JZGX lowers IL-6, indicating reduced inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interaction.", "mechanism": "Pro-inflammatory cytokine elevated in CAD; JZGX lowers TNF-\u03b1, indicating anti-inflammatory effect.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206304" }, { "confidence": "medium", "disease": "Myocardial Injury", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Released during myocardial damage; JZGX reduces CK-MB, indicating myocardial protection.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC11206304" }, { "confidence": "medium", "disease": "Myocardial Injury", "glycan_involvement": "Glycosylation affects protein stability and detection.", "mechanism": "Released during cardiac injury; JZGX lowers cTnT, reflecting reduced myocardial damage.", "protein": "cTnT", "relationship_type": "biomarker", "source_pmcid": "PMC11206304" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Integrin binding via glycosylated domains modulates cell adhesion.", "mechanism": "Fn-based LbL films suppress monocyte activation and reduce platelet adhesion, lowering thrombosis risk.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", 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"source_pmcid": "PMC11206333" }, { "confidence": "high", "disease": "Fibrosis (foreign body response)", "glycan_involvement": "Glycosylation affects collagen fibril formation and cell recognition.", "mechanism": "COL/HA LbL films reduce fibrosis thickness and macrophage aggregation at implant sites.", "protein": "Collagen (Type I/IV)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206333" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Retains glycosylation motifs from collagen, influencing cell adhesion.", "mechanism": "Gel/HA LbL films on ligament grafts suppress chronic inflammatory response and promote vascularization.", "protein": "Gelatin", "relationship_type": "protective", "source_pmcid": "PMC11206333" }, { "confidence": "medium", "disease": "Restenosis", "glycan_involvement": "Glycosylation modulates elastin receptor interactions.", "mechanism": "ELP-based LbL films promote endothelialization of stents, reducing restenosis risk.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "protective", "source_pmcid": "PMC11206333" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation reduces non-specific protein adsorption.", "mechanism": "BSA/PEI and BSA/HEP LbL films reduce platelet adhesion and coagulation activation on blood-contacting surfaces.", "protein": "Bovine Serum Albumin (BSA)", "relationship_type": "protective", "source_pmcid": "PMC11206333" }, { "confidence": "high", "disease": "Bacterial infection (biofilm formation)", "glycan_involvement": "Glycosylation stabilizes lysozyme structure and activity.", "mechanism": "COL/Ly LbL films kill Gram-positive and Gram-negative bacteria via enzymatic cell wall degradation.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206333" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may affect binding efficiency.", "mechanism": "Streptavidin/biotin-heparin LbL films reduce platelet adhesion and enhance clotting time.", "protein": "Streptavidin", "protein_enriched": { "function": "The biological function of streptavidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of streptavidin)", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22629" }, "relationship_type": "protective", "source_pmcid": "PMC11206333" }, { "confidence": "medium", "disease": "Wound healing", "glycan_involvement": "Keratan sulfate glycosylation modulates cell proliferation.", "mechanism": "COL/lumican LbL films promote hepatic stellate cell differentiation and tissue regeneration.", "protein": "Lumican", "protein_enriched": { "function": "", "gene_name": "LUM", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02315DX", "G02528FI", "G02628JF", "G02815KT", "G02886BB", "G03382KH", "G03644CB", "G04657PL", "G04672QB", "G04854VP", "G05049YU", "G05962QB", "G06110VR", "G06356OH", "G07246CJ", "G07755XJ", "G07810QS", "G08146BT", "G08290VR", "G08293MJ", "G08609CW", "G08918WF", "G09831WQ", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12341GU", "G12745LE", "G13191RB", "G14972EH", "G14994KB", "G15127JD", "G15664MX", "G16125XL", "G17208MA", "G18647XP", "G19385TO", "G20528HD", "G20706XG", "G22310AV", "G22625SJ", "G23294PN", "G23505EP", "G23719VF", "G23863VK", "G24528MX", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26377UA", "G26403SG", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G29299MO", "G29545VG", "G30221QT", "G30769VJ", "G30970QQ", "G31309XD", "G31544HA", "G31596VW", "G31852PQ", "G31986NC", "G32788FZ", "G32926LW", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G37881RL", "G39446WN", "G39471UU", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41840AI", "G41882MT", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44211QA", "G44215PV", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G45526EA", "G46450MZ", "G46524LG", "G46691LC", "G47518TP", "G47644PP", "G47702MW", "G48414YA", "G49739MP", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G51640FO", "G51653BI", "G52527GH", "G54010QB", "G55132BD", "G56307ZW", "G57776ZS", "G57776ZU", "G57888GL", "G58954YZ", "G59324HL", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G60967DT", "G61256FT", "G62461SM", "G62765YT", "G63041LO", "G63136LV", "G63381RX", "G63980BQ", "G64394MX", "G64751KD", "G65019XG", "G65184UU", "G65414LI", "G65807AE", "G66621EA", "G66766XF", "G67164EE", "G68490OW", "G68735SN", "G69107AL", "G69521XL", "G70101JE", "G70223PD", "G70232NH", "G70375MX", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71051TA", "G71463BG", "G72291OX", "G72667IM", "G72747WU", "G72790NZ", "G72797UR", "G72951AH", "G73686WG", "G73968GN", "G74430RZ", "G75006KF", "G75418YA", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G76868JS", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81637OR", "G82443XX", "G82463GQ", "G82830MN", "G83229XP", "G83555HU", "G83646BJ", "G83951ZY", "G84225JN", "G84452RH", "G84492TS", "G85144OK", "G85282JO", "G85554PZ", "G85740DB", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G87389XI", "G87661QW", "G88374WZ", "G88891KO", "G89045VA", "G90093AU", "G90382BL", "G90659AW", "G91473PK", "G91636VS", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94310CV", "G94470IW", "G94665LC", "G95046LV", "G95177YH", "G95865ZB", "G95977AE", "G96091TT", "G96577RX", "G98129XB", "G98611JV", "G99668VU", "G05724UK", "G06247RL", "G13910DJ", "G30740WO", "G36379GD", "G41247ZX", "G41271HD", "G56518TU", "G63040RU", "G64527OM", "G65344XH", "G66537LK", "G73027HY", "G85966UN", "G89827JR", "G99679NM", "G49108TO", "G09700PF", "G15169WU", "G23165GD", "G39595FH", "G49642SA", "G57581QG", "G69834CE", "G74381CZ", "G83633GK", "G85677PP", "G94831VI", "G43417UB", "G12261QD", "G13131HA", "G14547CB", "G16136DL", "G20312EM", "G30248BL", "G47950XN", "G49589RB", "G52848YE", "G53075ES", "G67506FN", "G72197KC", "G78502KD", "G81124ET", "G83460ZZ", "G84862VB", "G92275SC" ], "uniprot_id": "P51884" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206333" }, { "confidence": "medium", "disease": "Chondrosarcoma", "glycan_involvement": "Glycosylation influences integrin-mediated cell specificity.", "mechanism": "Fn-grafted LbL films promote chondrocyte adhesion and suppress chondrosarcoma cell growth.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206375" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation influences LF's immune modulation and receptor interactions.", "mechanism": "Neutrophil-derived LF release correlates with serum-specific IgE and asthma severity; exogenous LF may modulate inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Atopic dermatitis", "glycan_involvement": "Altered glycosylation may affect LF's function in skin immunity.", "mechanism": "Elevated circulating LF in patients; may reflect or contribute to disease pathogenesis.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206375" }, { "confidence": "high", "disease": "Chronic rhinosinusitis with nasal polyposis (CRSwNP)", "glycan_involvement": "Not specified.", "mechanism": "LF deficiency in mucosa is associated with CRSwNP; LTF gene polymorphism increases risk, especially with allergy/asthma.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Crohn\u2019s disease", "glycan_involvement": "Glycosylation affects LF's stability and interaction with microbiota.", "mechanism": "LF modulates gut flora and reduces intestinal inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", 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"G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation impacts LF's anti-inflammatory properties.", "mechanism": "LF reduces intestinal inflammation and modulates immune response.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", 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"G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Not specified.", "mechanism": "LF promotes regulatory T cells, aiding immune tolerance and neuroprotection.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Not specified.", "mechanism": "LTF gene polymorphisms (Thr29Ala, Arg47Lys) in N-terminal region associated with disease susceptibility.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "causal", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "CD14 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "CD14 gene polymorphisms influence Th1/Th2 balance and atopy risk; sCD14 in breast milk linked to atopic disease development.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "genetic modifier/biomarker", "source_pmcid": "PMC11206375" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "ITLN1 is a glycoprotein; glycosylation may affect allergen recognition.", "mechanism": "ITLN1 upregulated in allergic airway inflammation; promotes Th2 cytokines and eosinophilia; SNPs linked to asthma risk.", "protein": "Intelectin 1 (ITLN1)", "protein_enriched": { "function": "May play a role in the defense system against pathogens", "gene_name": "ITLN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WWU7" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11206375" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "VEGF-A is a glycoprotein; glycosylation affects its secretion and receptor binding.", "mechanism": "VEGF-A promotes angiogenesis in ovarian cancer; inhibition reduces tumor vascularization.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Bevacizumab is a glycosylated monoclonal antibody; glycosylation affects stability and efficacy.", "mechanism": "Bevacizumab binds VEGF-A, blocking angiogenesis and improving progression-free survival.", "protein": "Bevacizumab", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Extensive O-glycosylation critical for antigenicity and detection.", "mechanism": "CA125 is elevated in ovarian cancer and used for diagnosis and monitoring.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "BRCA1 mutation confers homologous recombination deficiency, sensitizing to PARP inhibitors.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "BRCA2 mutation confers homologous recombination deficiency, sensitizing to PARP inhibitors.", "protein": "BRCA2", "protein_enriched": { "function": "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by ", "gene_name": "BRCA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G03238UC", "G37399XV", "G41247ZX", "G90382BL", "G49108TO" ], "uniprot_id": "P51587" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "PARP1 inhibition induces synthetic lethality in HR-deficient ovarian cancer cells.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206378" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation affects stability and half-life.", "mechanism": "Serum albumin levels used to monitor patient status and therapy toxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206378" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects iron binding and serum half-life.", "mechanism": "Transferrin levels reflect iron status; anemia is a common PARPi side effect.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206378" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation affects enzyme activity and membrane localization.", "mechanism": "Monitored for liver toxicity during therapy.", "protein": "Gamma glutamyltransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect immunogenicity and side effect profile.", "mechanism": "Bevacizumab therapy increases risk of hypertension as an adverse effect.", "protein": "Bevacizumab", "relationship_type": "causal", "source_pmcid": "PMC11206378" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; glycosylation status indicates glucose control.", "mechanism": "HbA1c reflects chronic hyperglycemia and is reduced by curcumin treatment.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "MCP-1 is glycosylated, affecting its stability and secretion.", "mechanism": "Curcumin reduces MCP-1, lowering inflammation and improving insulin sensitivity.", "protein": "Monocyte Chemoattractant Protein-1 (MCP-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "IL-6 glycosylation modulates its activity and receptor binding.", "mechanism": "IL-6 promotes insulin resistance; curcumin suppresses IL-6 production.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "TNF-\u03b1 glycosylation affects its bioactivity.", "mechanism": "TNF-\u03b1 induces insulin resistance; curcumin inhibits TNF-\u03b1 secretion.", "protein": "Tumor Necrosis Factor Alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC11206386" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "TGF-\u03b21 glycosylation is essential for secretion and function.", "mechanism": "TGF-\u03b21 promotes cardiac fibrosis in diabetes; curcumin inhibits TGF-\u03b21.", "protein": "Transforming Growth Factor Beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Adiponectin is heavily glycosylated, required for multimerization and activity.", "mechanism": "Adiponectin improves insulin sensitivity; curcumin increases adiponectin levels.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "AGEs are non-enzymatic glycosylation products of proteins.", "mechanism": "AGEs contribute to diabetic complications; curcumin reduces AGE formation.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC11206386" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "CRP glycosylation affects its stability and function.", "mechanism": "CRP is an inflammatory marker elevated in T2DM; curcumin lowers CRP.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206386" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLUT4 is N-glycosylated, required for proper trafficking.", "mechanism": "GLUT4 mediates glucose uptake; curcumin upregulates GLUT4 expression.", "protein": "Glucose Transporter 4 (GLUT4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206386" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "IAPP can be glycosylated, affecting aggregation propensity.", "mechanism": "IAPP aggregation contributes to \u03b2-cell dysfunction; curcumin reduces circulating IAPP.", "protein": "Islet Amyloid Polypeptide (IAPP)", "relationship_type": "causal", "source_pmcid": "PMC11206386" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ADAM10 folding and function.", "mechanism": "ADAM10 activity promotes inflammation and plaque formation; inhibition reduces atherosclerosis.", "protein": "ADAM10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ADAM17 trafficking and activity.", "mechanism": "ADAM17 mediates shedding of inflammatory cytokines; inhibition reduces plaque and inflammation.", "protein": "ADAM17", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation required for sortilin stability and trafficking.", "mechanism": "Sortilin regulates hepatic lipoprotein metabolism and VLDL secretion; increased sortilin promotes dyslipidemia.", "protein": "Sortilin", "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation impacts sortilin's function in lipoprotein handling.", "mechanism": "Sortilin promotes atherosclerotic plaque development via effects on lipid metabolism.", "protein": "Sortilin", "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation required for ADAM10 enzymatic activity.", "mechanism": "ADAM10 upregulation increases hepatic lipid accumulation; inhibition reduces steatosis.", "protein": "ADAM10", "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes vascular inflammation and plaque formation; regulated by ADAM17.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates IL-6R function.", "mechanism": "IL-6 drives inflammatory signaling in atherosclerosis; ADAM10/17 mediate IL-6R shedding.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences IL-1\u03b2 receptor activity.", "mechanism": "IL-1\u03b2 is a key inflammatory mediator in plaque development; ADAM10/17 regulate IL-1R shedding.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11206409" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation stabilizes PON-1 in serum.", "mechanism": "PON-1 has antioxidant activity, reducing lipid oxidation and plaque formation.", "protein": "PON-1", "relationship_type": "protective", "source_pmcid": "PMC11206409" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects PLA2 secretion.", "mechanism": "PLA2 is elevated in rupture-prone plaques and reflects inflammation.", "protein": "PLA2", "relationship_type": "biomarker", "source_pmcid": "PMC11206409" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "FAP is a glycoprotein; glycosylation is required for its membrane localization and enzymatic activity.", "mechanism": "FAP is upregulated in activated fibroblasts during tissue remodeling and fibrosis in ILD; FAPI PET detects this activity.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "high", "disease": "Systemic Sclerosis-associated ILD", "glycan_involvement": "Glycosylation supports FAP\u2019s cell surface expression in fibrotic tissue.", "mechanism": "FAP expression correlates with disease extent and progression; FAPI PET uptake predicts risk and monitors response to antifibrotic therapy.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "high", "disease": "IgG4-Related Disease (IgG4-RD)", "glycan_involvement": "FAP glycosylation is necessary for its function in fibro-inflammatory tissue.", "mechanism": "FAP is expressed in fibrotic lesions of IgG4-RD; FAPI PET distinguishes fibrotic from inflammatory stages.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "high", "disease": "Crohn\u2019s Disease", "glycan_involvement": "Glycosylation enables FAP\u2019s activity in intestinal tissue remodeling.", "mechanism": "FAP is upregulated in fibroblasts in fibrotic segments; FAPI PET differentiates fibrosis from active inflammation.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "high", "disease": "Bone and Joint Infection", "glycan_involvement": "FAP glycosylation is essential for its extracellular matrix remodeling function.", "mechanism": "FAP is induced in fibroblasts during infection and biofilm formation; FAPI PET differentiates infection from aseptic failure.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "medium", "disease": "Long-COVID Lung Alterations", "glycan_involvement": "Glycosylation maintains FAP\u2019s activity in fibrotic lung tissue.", "mechanism": "FAP is upregulated in fibroblasts during post-infectious fibrotic repair; FAPI PET detects chronic fibrotic changes not seen with FDG.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation is required for FAP\u2019s function in synovial tissue.", "mechanism": "FAP is overexpressed in synovial activated fibroblasts; FAPI PET visualizes fibroblast-driven inflammation.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "medium", "disease": "Thyroiditis", "glycan_involvement": "FAP glycosylation supports its role in tissue remodeling.", "mechanism": "FAP is expressed in activated fibroblasts during thyroid inflammation; FAPI PET detects fibrotic/inflammatory changes.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation is necessary for FAP\u2019s cell surface activity in myocardium.", "mechanism": "FAP is upregulated in cardiac fibroblasts during inflammatory remodeling; FAPI PET visualizes fibrotic activity.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "medium", "disease": "Light-chain Cardiac Amyloidosis", "glycan_involvement": "FAP glycosylation is required for its function in cardiac tissue.", "mechanism": "FAP is expressed in fibroblasts involved in amyloid-associated cardiac fibrosis; FAPI PET detects fibrotic remodeling.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206476" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from APP, a glycoprotein; glycosylation affects APP processing and A\u03b2 production.", "mechanism": "A\u03b2 aggregation is central to AD pathology; increased plasma A\u03b2 is associated with disease progression.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE is glycosylated; glycosylation modulates lipid binding and A\u03b2 interaction.", "mechanism": "ApoE4 allele increases AD risk by affecting A\u03b2 clearance and aggregation.", "protein": "Apolipoprotein E4 (ApoE4)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AChE is N-glycosylated, which affects its stability and localization.", "mechanism": "AChE degrades acetylcholine, contributing to cognitive decline; inhibition improves symptoms.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Subjective memory impairment (SMI)", "glycan_involvement": "N-glycosylation modulates AChE function in the brain.", "mechanism": "Elevated AChE is associated with memory impairment; reduction improves memory.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "BDNF is glycosylated, which influences secretion and activity.", "mechanism": "BDNF supports neuronal survival and synaptic plasticity; reduced levels are linked to AD.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its inflammatory activity.", "mechanism": "Elevated hs-CRP reflects systemic inflammation, which is associated with AD risk.", "protein": "High-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "APP glycosylation influences A\u03b2 generation.", "mechanism": "Increased plasma A\u03b2 is associated with progression from MCI to AD.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Glycosylation modulates ApoE4 function in the CNS.", "mechanism": "ApoE4 genotype increases risk of MCI progression to AD.", "protein": "Apolipoprotein E4 (ApoE4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206504" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "N-glycosylation affects AChE's enzymatic activity.", "mechanism": "AChE inhibitors are used to treat dementia symptoms by increasing acetylcholine.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206504" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "CRP glycosylation modulates its role in inflammation.", "mechanism": "Elevated hs-CRP is associated with increased risk of dementia.", "protein": "High-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206504" }, { "confidence": "high", "disease": "Hepatic steatosis (NAFLD)", "glycan_involvement": "AST is glycosylated, affecting its stability and secretion.", "mechanism": "Elevated AST levels indicate hepatocyte injury and progression of hepatic steatosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11206563" }, { "confidence": "high", "disease": "Hepatic steatosis (NAFLD)", "glycan_involvement": "ALT glycosylation influences its serum levels.", "mechanism": "Elevated ALT levels reflect liver damage in NAFLD and NASH.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206563" }, { "confidence": "medium", "disease": "Hepatic steatosis (NAFLD)", "glycan_involvement": "SREBP-1c glycosylation modulates its activity and stability.", "mechanism": "SREBP-1c activation increases lipogenesis, contributing to hepatic lipid accumulation.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206563" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "TNF-\u03b1 glycosylation affects receptor binding and signaling.", "mechanism": "TNF-\u03b1 promotes inflammation and inhibits IRS activation, leading to insulin resistance.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206563" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "IL-6 glycosylation regulates its secretion and activity.", "mechanism": "IL-6 inhibits IRS activation, contributing to insulin resistance in obesity.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11206563" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "IRS glycosylation modulates its signaling capacity.", "mechanism": "IRS inhibition by TNF-\u03b1/IL-6 leads to impaired insulin signaling.", "protein": "IRS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206563" }, { "confidence": "medium", "disease": "Hepatic steatosis (NAFLD)", "glycan_involvement": "CYP enzymes are glycosylated, influencing their activity.", "mechanism": "Ce6-PDT inhibits CYP enzymes, potentially affecting drug metabolism in NAFLD.", "protein": "Cytochrome P450 enzymes", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206563" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "AMPK glycosylation affects its activation and metabolic regulation.", "mechanism": "Ce6-PDT activates AMPK, reducing adipocyte growth and lipid accumulation.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206563" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL glycoprotein components affect receptor interactions.", "mechanism": "Elevated LDL is associated with obesity and hepatic steatosis; Ce6-PDT reduces LDL levels.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC11206563" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL glycoprotein components modulate lipid transport.", "mechanism": "HDL levels are monitored in obesity and NAFLD; Ce6-PDT does not affect HDL.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC11206563" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP levels are elevated in psoriasis, reflecting systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "TNF-\u03b1 is glycosylated, which modulates its receptor binding and activity.", "mechanism": "TNF-\u03b1 drives keratinocyte proliferation and chronic inflammation in psoriasis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "IL-6 glycosylation affects secretion and receptor interaction.", "mechanism": "IL-6 is elevated in psoriasis and promotes inflammatory signaling.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "IL-1\u03b2 glycosylation influences its stability and activity.", "mechanism": "IL-1\u03b2 is involved in skin inflammation and keratinocyte activation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "IL-17 glycosylation modulates immune cell interactions.", "mechanism": "IL-17/IL-23 axis is central to psoriasis pathogenesis.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation is essential for adiponectin multimerization and function.", "mechanism": "Adiponectin is anti-inflammatory; reduced in obesity, contributing to inflammation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11206573" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation affects receptor binding and signaling.", "mechanism": "Leptin is pro-inflammatory and elevated in obesity, promoting psoriasis severity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP is a risk marker for cardiovascular comorbidities in psoriasis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206573" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease", "glycan_involvement": "IL-6 glycosylation affects hepatic signaling.", "mechanism": "IL-6 promotes hepatic inflammation and is elevated in psoriasis with liver dysfunction.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11206573" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation required for adiponectin's insulin-sensitizing effects.", "mechanism": "Low adiponectin in obesity and psoriasis increases risk of diabetes.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11206573" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "IL-6 is glycosylated, affecting its stability and secretion.", "mechanism": "Elevated IL-6 levels correlate with neuroinflammation and AD pathogenesis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and activity.", "mechanism": "Increased TNF-\u03b1 drives neuroinflammatory responses in AD.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "CCL2 glycosylation influences chemotactic activity.", "mechanism": "Altered CCL2 levels found in severe depression; normalization with treatment.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "CXCL10 glycosylation affects receptor interaction.", "mechanism": "Elevated CXCL10 in AD patients' blood and CSF; linked to neuronal apoptosis.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "CCL3 glycosylation modulates immune cell recruitment.", "mechanism": "CCL3 is highly expressed during CNS inflammation in MS.", "protein": "CCL3", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependen", "gene_name": "CCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10147" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CXCL2 glycosylation regulates neutrophil chemotaxis.", "mechanism": "CXCL2 is elevated in AD and ALS, indicating neuroinflammation.", "protein": "CXCL2", "protein_enriched": { "function": "Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-", "gene_name": "CXCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19875" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "GPR55 is glycosylated, impacting receptor trafficking and signaling.", "mechanism": "GPR55 modulation (agonists/antagonists) affects motor symptoms and neuroinflammation.", "protein": "GPR55", "protein_enriched": { "function": "G-protein coupled receptor that binds to several ligands including 2-arachidonoyl lysophosphatidylinositol or lysophosphatidylglucoside with high affinity, leading to rapid and transient activation of", "gene_name": "GPR55", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9Y2T6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may affect GPR55 function in CNS.", "mechanism": "GPR55 activation reduces depressive-like behavior and normalizes inflammatory markers.", "protein": "GPR55", "protein_enriched": { "function": "G-protein coupled receptor that binds to several ligands including 2-arachidonoyl lysophosphatidylinositol or lysophosphatidylglucoside with high affinity, leading to rapid and transient activation of", "gene_name": "GPR55", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9Y2T6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206594" }, { "confidence": "low", "disease": "Bipolar disorder", "glycan_involvement": "CCL3 glycosylation modulates immune signaling.", "mechanism": "CCL3 is involved in CNS inflammation in bipolar disorder.", "protein": "CCL3", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependen", "gene_name": "CCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10147" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "CXCL10 glycosylation affects immune cell recruitment.", "mechanism": "CXCL10 elevated in CSF of MS patients; correlates with intrathecal inflammation.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206594" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "SREBP-1 is glycosylated, which may affect its stability and activity.", "mechanism": "MLP peptides downregulate SREBP-1, reducing lipogenesis and fat accumulation.", "protein": "SREBP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MLP peptides activate AMPK, promoting fatty acid oxidation and reducing lipid synthesis.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "FAS is glycosylated, which may regulate its enzymatic activity.", "mechanism": "MLP peptides suppress FAS expression, decreasing fatty acid synthesis.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "ACC is glycosylated, affecting its function.", "mechanism": "MLP peptides downregulate ACC, reducing malonyl-CoA and lipogenesis.", "protein": "ACC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Adiponectin is heavily glycosylated, essential for its secretion and function.", "mechanism": "Adiponectin levels are altered in obesity and diabetes; MLP modulates its serum levels.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects its stability and secretion.", "mechanism": "MLP peptides reduce TNF-\u03b1 levels, alleviating obesity-related inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "MCP-1 glycosylation modulates its chemotactic activity.", "mechanism": "MLP peptides decrease MCP-1, reducing macrophage infiltration in adipose tissue.", "protein": "MCP-1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Insulin glycosylation is not typical; proinsulin may be glycosylated.", "mechanism": "MLP peptides improve insulin sensitivity and lower serum insulin levels.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "PEPCK is glycosylated, which may affect its activity.", "mechanism": "MLP peptides downregulate PEPCK, reducing gluconeogenesis and improving glucose tolerance.", "protein": "PEPCK", "protein_enriched": { "function": "Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:2486", "gene_name": "PCK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35558" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "G6Pase glycosylation is important for its function.", "mechanism": "MLP peptides suppress G6Pase expression, decreasing hepatic glucose output.", "protein": "G6Pase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206624" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for receptor function and cell surface expression.", "mechanism": "Upregulation of Cntfr reduces adiposity and body weight, possibly via leptin-independent signaling.", "protein": "Cntfr", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor stability and signaling.", "mechanism": "Hrh1 gene variants and upregulation are associated with body mass index and weight gain.", "protein": "Hrh1", "relationship_type": "biomarker", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates cell surface expression and function.", "mechanism": "Upregulation of Ramp3 is linked to reduced obesity, especially in estrogen-deficient/postmenopausal states.", "protein": "Ramp3", "relationship_type": "protective", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Reduced Atrn expression suppresses agouti-induced obesity and decreases adiposity.", "protein": "Atrn", "relationship_type": "causal", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor activity.", "mechanism": "Adipor1 expression correlates with BMI and metabolic dysfunction; downregulation is beneficial.", "protein": "Adipor1", "relationship_type": "biomarker", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates enzyme stability.", "mechanism": "Ptpn1 inhibition confers resistance to weight gain and improves insulin sensitivity.", "protein": "Ptpn1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation essential for MHC class I assembly.", "mechanism": "Elevated serum B2m is associated with overweight/obesity and adverse metabolic outcomes.", "protein": "B2m", "relationship_type": "biomarker", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for trafficking and function.", "mechanism": "Sort1 downregulation leads to lower body weight and visceral fat, improved glucose uptake.", "protein": "Sort1", "relationship_type": "protective", "source_pmcid": "PMC11206641" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation critical for receptor maturation and signaling.", "mechanism": "Insr expression is linked to insulin resistance and type 2 diabetes; downregulation improves glucose homeostasis.", "protein": "Insr", "relationship_type": "causal", "source_pmcid": "PMC11206641" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Il6ra expression correlates with increased fat mass and inflammation; downregulation is beneficial.", "protein": "Il6ra", "relationship_type": "biomarker", "source_pmcid": "PMC11206641" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is a glycoprotein; glycosylation may affect aggregation and clearance.", "mechanism": "A\u03b2 aggregation forms amyloid plaques, a hallmark of AD pathology.", "protein": "Amyloid-\u03b2 (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC11206655" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; altered glycosylation may promote aggregation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to neuronal dysfunction.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation affects receptor function.", "mechanism": "TREM2 modulates microglial activation and amyloid clearance.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD38 is glycosylated; glycosylation may regulate its enzymatic activity.", "mechanism": "CD38-targeting antibodies modulate neuroinflammation and immune response.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation influences secretion and activity.", "mechanism": "Inhibition of IL-1\u03b2 reduces neuroinflammatory damage in AD.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates receptor binding.", "mechanism": "Inhibition of TNF-\u03b1 reduces neuroinflammation and neuronal damage.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "BDNF is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "BDNF enhances neuronal survival and synaptic plasticity, counteracting AD pathology.", "protein": "Brain-derived neurotrophic factor (BDNF)", "protein_enriched": { "function": "Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of ", "gene_name": "BDNF", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P23560" }, "relationship_type": "protective", "source_pmcid": "PMC11206655" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "NGF is glycosylated; glycosylation is critical for stability and activity.", "mechanism": "NGF supports neuronal survival and function; therapeutic enhancement may slow AD progression.", "protein": "Nerve growth factor (NGF)", "protein_enriched": { "function": "Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1 and NGFR rece", "gene_name": "NGF", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01138" }, "relationship_type": "protective", "source_pmcid": "PMC11206655" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "MARCKS is glycosylated; glycosylation may affect membrane association.", "mechanism": "MARCKS is implicated in phase separation dysregulation in AD; targeting may restore cellular homeostasis.", "protein": "MARCKS", "protein_enriched": { "function": "Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/o", "gene_name": "MARCKS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29966" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "CAMKK2 is glycosylated; glycosylation may regulate kinase activity.", "mechanism": "CAMKK2 is involved in AD-related signaling pathways; inhibition may be therapeutic.", "protein": "CAMKK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206655" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation modulates immune cell function and trafficking.", "mechanism": "Elevated white blood cell count is associated with increased T2D risk; B vitamin intake reduces inflammation and WBC count.", "protein": "White blood cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation affects lymphocyte activation and signaling.", "mechanism": "Altered lymphocyte percentage mediates the effect of B vitamins on T2D risk.", "protein": "Lymphocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Basophil surface glycoproteins regulate inflammatory responses.", "mechanism": "Basophil percentage mediates B vitamin protection against T2D.", "protein": "Basophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Neutrophil glycosylation modulates adhesion and migration.", "mechanism": "Neutrophil percentage and count are inflammatory mediators linking B vitamin intake to T2D risk.", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "low", "disease": "Type 2 diabetes", "glycan_involvement": "Albumin glycosylation status changes in diabetes.", "mechanism": "Serum albumin levels are altered in inflammation and T2D.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "low", "disease": "Type 2 diabetes", "glycan_involvement": "Globulin glycosylation patterns change in chronic inflammation.", "mechanism": "Serum globulin levels reflect inflammatory status in T2D.", "protein": "Serum globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation regulates immune cell interactions.", "mechanism": "WBC count is a direct marker of systemic inflammation.", "protein": "White blood cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates lymphocyte trafficking.", "mechanism": "Lymphocyte percentage reflects immune activation.", "protein": "Lymphocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects neutrophil-endothelial interactions.", "mechanism": "Neutrophil count is a marker of acute inflammation.", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Surface glycoproteins mediate basophil function.", "mechanism": "Basophil percentage indicates allergic and inflammatory responses.", "protein": "Basophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11206684" }, { "confidence": "high", "disease": "PCOS", "glycan_involvement": "SHBG is a glycoprotein; glycosylation affects its stability and hormone binding.", "mechanism": "Lower SHBG levels are associated with increased free androgen index in PCOS.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "LH is a glycoprotein; glycosylation modulates receptor interaction and half-life.", "mechanism": "Negative correlation between RBC folate and LH levels in PCOS.", "protein": "LH", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "AMH is a glycoprotein; glycosylation is important for secretion and activity.", "mechanism": "Vitamin B12 levels negatively correlate with AMH in PCOS.", "protein": "AMH", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "low", "disease": "PCOS", "glycan_involvement": "FR\u03b1 is a glycoprotein; glycosylation affects folate binding and cell surface expression.", "mechanism": "FR\u03b1 may be activated by testosterone, linking folate metabolism to androgen excess in PCOS.", "protein": "FR\u03b1", "relationship_type": "causal", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "TCN2 is a glycoprotein; glycosylation is essential for B12 transport.", "mechanism": "Low vitamin B12 (carried by TCN2) increases risk of anemia in PCOS.", "protein": "Transcobalamin (TCN2)", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "LDLc is a glycoprotein; glycosylation affects particle stability and receptor binding.", "mechanism": "Vitamin B12 positively correlates with LDLc in PCOS, suggesting a role in lipid metabolism.", "protein": "LDLc", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "high", "disease": "PCOS", "glycan_involvement": "HDLc is a glycoprotein; glycosylation modulates function and clearance.", "mechanism": "HDLc levels are 23% lower in PCOS, indicating dyslipidemia.", "protein": "HDLc", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "MTHFR polymorphisms affect folate metabolism and homocysteine levels, but not directly associated with PCOS in this cohort.", "protein": "MTHFR", "relationship_type": "causal", "source_pmcid": "PMC11206694" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects SHBG serum levels and function.", "mechanism": "Lower SHBG is associated with higher BMI and metabolic disturbances in PCOS.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates LH bioactivity.", "mechanism": "Negative correlation between RBC folate and LH may reflect hormonal-metabolic interplay in PCOS.", "protein": "LH", "relationship_type": "biomarker", "source_pmcid": "PMC11206694" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune function.", "mechanism": "CRP is elevated in diabetes, promotes inflammation and inhibits insulin-mediated glucose transport.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "IL-1 is glycosylated; glycosylation modulates cytokine activity and receptor binding.", "mechanism": "IL-1 promotes inflammation, impairs insulin signaling, and contributes to \u03b2-cell loss.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "DPP-IV is heavily glycosylated; glycosylation is essential for enzymatic activity and cell surface localization.", "mechanism": "DPP-IV cleaves incretin hormones (GLP-1, GIP), reducing insulin secretion and glucose homeostasis.", "protein": "Dipeptidyl peptidase-4 (DPP-IV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "SGLT-1 is glycosylated; glycosylation affects transporter stability and function.", "mechanism": "SGLT-1 mediates intestinal and renal glucose absorption; overexpression increases hyperglycemia.", "protein": "Sodium\u2013glucose co-transporter-1 (SGLT-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Some PTPs are glycosylated; glycosylation can modulate activity and localization.", "mechanism": "PTP overexpression negatively regulates insulin signaling by dephosphorylating insulin receptor substrates.", "protein": "Protein tyrosine phosphatase (PTP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of CRP influences its interaction with immune cells and vascular tissues.", "mechanism": "Elevated CRP in diabetes is associated with increased cardiovascular risk due to inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206732" }, { "confidence": "medium", "disease": "Cancer (hepatocellular carcinoma)", "glycan_involvement": "Glycosylation of DPP-IV modulates its activity and cell surface expression in tumors.", "mechanism": "DPP-IV activity is implicated in cancer cell proliferation and immune evasion.", "protein": "DPP-IV", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "medium", "disease": "Cancer (hepatocellular carcinoma)", "glycan_involvement": "Glycosylation affects IL-1 secretion and receptor interaction in tumor microenvironment.", "mechanism": "IL-1 promotes tumor-associated inflammation and cancer progression.", "protein": "IL-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "medium", "disease": "Cancer (hepatocellular carcinoma)", "glycan_involvement": "Glycosylation is required for SGLT-1 membrane localization in cancer cells.", "mechanism": "SGLT-1 supports cancer cell glucose uptake and proliferation.", "protein": "SGLT-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206732" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation status may affect DPP-IV levels and activity in serum.", "mechanism": "Elevated DPP-IV is a marker of impaired incretin function in diabetes.", "protein": "DPP-IV", "relationship_type": "biomarker", "source_pmcid": "PMC11206732" }, { "confidence": "high", "disease": "Malnutrition-related liver steatosis", "glycan_involvement": "Albumin glycosylation affects stability and function; hypoalbuminemia may reflect altered glycosylation.", "mechanism": "Low serum albumin reflects poor protein reserves and correlates with severity of steatosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "high", "disease": "Malnutrition-related liver steatosis", "glycan_involvement": "Lipoproteins are glycosylated; altered glycosylation may affect lipid transport.", "mechanism": "Low cholesterol is part of CONUT score and indicates caloric depletion, associated with steatosis.", "protein": "Total Cholesterol (LDL/HDL)", "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Cell surface glycoproteins mediate immune response; glycosylation affects lymphocyte function.", "mechanism": "Low lymphocyte count (CONUT score) independently predicts sepsis risk in malnourished patients.", "protein": "Peripheral Lymphocyte", "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Malnutrition-related liver steatosis", "glycan_involvement": "CRP is glycosylated; glycan changes modulate inflammatory activity.", "mechanism": "Elevated CRP correlates with inflammation and severity of steatosis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects procalcitonin stability and secretion.", "mechanism": "Higher procalcitonin levels trend with increased sepsis risk in severe steatosis.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Malnutrition-related liver steatosis", "glycan_involvement": "Glycosylation may affect enzyme activity and release.", "mechanism": "Elevated AST indicates hepatocellular injury in steatosis.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Malnutrition-related liver steatosis", "glycan_involvement": "Glycosylation may modulate enzyme function.", "mechanism": "ALT elevation reflects liver injury in steatosis.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "low", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation affects peptide stability and clearance.", "mechanism": "NT-proBNP elevation may indicate cardiac stress in chronic liver disease.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Healthcare-related infections", "glycan_involvement": "Glycosylation modulates immune cell interactions.", "mechanism": "Altered glycoprotein expression may impair immune defense, increasing infection risk.", "protein": "White Blood Cell Surface Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Thromboembolic risk", "glycan_involvement": "Glycosylation may affect albumin's anticoagulant properties.", "mechanism": "Low albumin is associated with increased thromboembolic risk in severe steatosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206738" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation may affect stability and bioactivity", "mechanism": "Reduces fasting blood glucose, improves insulin resistance in T2D mice", "protein": "Pea glycoprotein PGP2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation may modulate receptor interactions", "mechanism": "Improves insulin sensitivity, reduces blood glucose and lipid levels", "protein": "\u03b3-conglutin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may influence peptide uptake and function", "mechanism": "Inhibits HMG-CoA reductase, modulates LDLR and PCSK9 pathways, lowers cholesterol", "protein": "Lupin protein hydrolysates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may affect peptide stability", "mechanism": "Downregulates HMG-CoA reductase, reduces triglyceride synthesis", "protein": "Chickpea peptides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect peptide bioactivity", "mechanism": "Inhibits ACE and renin, lowers blood pressure in hypertensive rats", "protein": "Mung bean protein hydrolysates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate peptide-receptor interactions", "mechanism": "Inhibits ACE, upregulates ACE2, lowers blood pressure", "protein": "Pea protein hydrolysates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect peptide function", "mechanism": "Inhibits ACE and renin, reduces systolic blood pressure", "protein": "Pigeon pea protein hydrolysates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may influence peptide stability", "mechanism": "Inhibits HMG-CoA reductase, lowers cholesterol in rats", "protein": "Cowpea protein hydrolysates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may affect peptide-receptor binding", "mechanism": "Inhibits HMG-CoA reductase and PCSK9, increases LDLR expression", "protein": "Lupin peptide T9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may modulate peptide activity", "mechanism": "Inhibits PCSK9 and HMG-CoA reductase, lowers cholesterol", "protein": "Lupin peptide P5-Best", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206746" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Albumin glycosylation may affect binding affinity for uremic toxins.", "mechanism": "IxS and pCS bind extensively to albumin; their serum levels rise with CKD progression and serve as biomarkers for renal dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation status may modulate toxin binding.", "mechanism": "Elevated IxS and pCS bound to albumin are associated with AKI onset.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "MRP4 glycosylation affects membrane localization and function.", "mechanism": "pCS inhibits MRP4, reducing renal excretion of toxins and drugs, worsening CKD.", "protein": "Multidrug resistance protein 4 (MRP4)", "relationship_type": "causal", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation critical for BCRP trafficking and activity.", "mechanism": "pCS inhibits BCRP, impairing renal clearance of endogenous and exogenous compounds.", "protein": "Breast cancer resistance protein (BCRP)", "relationship_type": "causal", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "TF glycosylation modulates procoagulant activity.", "mechanism": "IxS increases TF activity via AHR, promoting thrombosis in CKD.", "protein": "Tissue Factor (TF)", "relationship_type": "causal", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Tubulointerstitial Fibrosis", "glycan_involvement": "TGF-\u03b21 glycosylation required for secretion and activity.", "mechanism": "IxS and pCS activate TGF-\u03b21 pathway, leading to renal fibrosis.", "protein": "Transforming Growth Factor Beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation of RAAS hormones affects receptor binding.", "mechanism": "IxS and pCS activate RAAS, contributing to kidney injury.", "protein": "Renin-Angiotensin-Aldosterone System (RAAS) components", "relationship_type": "causal", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may influence toxin binding and vascular effects.", "mechanism": "Serum levels of albumin-bound IxS and pCS correlate with CVD risk in CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206749" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Albumin glycosylation may modulate vascular interactions.", "mechanism": "Elevated plasma pCS (albumin-bound) associated with increased risk of ischemic stroke in hemodialysis patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206749" }, { "confidence": "low", "disease": "Colonic Cancer", "glycan_involvement": "Glycosylation may affect albumin's interaction with toxins and cancer cells.", "mechanism": "IxS and pCS (albumin-bound) are associated with increased risk of colonic cancer in CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206749" }, { "confidence": "high", "disease": "Hyperlipidaemia", "glycan_involvement": "LDL particles contain glycoproteins (ApoB) whose glycosylation affects clearance.", "mechanism": "Elevated LDL-C is a key marker and risk factor for hyperlipidaemia.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of LDL-associated proteins modulates receptor binding and uptake.", "mechanism": "High LDL-C promotes atherosclerotic plaque formation.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL contains glycoproteins (ApoA-I) with glycosylation affecting function.", "mechanism": "High HDL-C is protective against CVD by promoting cholesterol efflux.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC11206754" }, { "confidence": "medium", "disease": "Fatty Liver Disease", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated ALT indicates hepatic injury due to lipid accumulation.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206754" }, { "confidence": "medium", "disease": "Fatty Liver Disease", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect activity.", "mechanism": "Elevated AST is a marker of liver injury in metabolic disease.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Hyperlipidaemia", "glycan_involvement": "Bile acid metabolism is regulated by glycoproteins (transporters, enzymes).", "mechanism": "Increased excretion of cholic acid reduces plasma cholesterol and LDL-C.", "protein": "Cholic Acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206754" }, { "confidence": "medium", "disease": "Hyperlipidaemia", "glycan_involvement": "Glycoproteins in the gut and liver regulate bile acid transformation.", "mechanism": "Conversion of cholic acid to deoxycholic acid reflects gut microbiota activity and bile acid metabolism.", "protein": "Deoxycholic Acid", "relationship_type": "biomarker", "source_pmcid": "PMC11206754" }, { "confidence": "medium", "disease": "Hyperlipidaemia", "glycan_involvement": "Glycoprotein enzymes mediate synthesis and transport.", "mechanism": "Altered levels indicate changes in bile acid metabolism in response to diet and spirulina.", "protein": "\u03b2-Muricholic Acid", "relationship_type": "biomarker", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of LDL-associated proteins affects uptake by macrophages.", "mechanism": "LDL-C accumulation in arterial walls drives atherosclerotic plaque formation.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycoprotein transporters regulate enterohepatic circulation.", "mechanism": "Increased fecal excretion of cholic acid lowers cholesterol, reducing CVD risk.", "protein": "Cholic Acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206754" }, { "confidence": "high", "disease": "Chronic Myeloid Leukemia (CML)", "glycan_involvement": "Glycosylation is essential for P-gp folding and function, impacting drug transport.", "mechanism": "P-gp mediates dasatinib efflux, affecting drug bioavailability and resistance in CML therapy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206811" }, { "confidence": "high", "disease": "Chronic Myeloid Leukemia (CML)", "glycan_involvement": "Glycosylation modulates BCRP stability and localization, influencing drug resistance.", "mechanism": "BCRP effluxes dasatinib, contributing to multidrug resistance in CML.", "protein": "Breast Cancer Resistance Protein (BCRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206811" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL), Philadelphia chromosome-positive", "glycan_involvement": "Glycosylation required for P-gp membrane trafficking and function.", "mechanism": "P-gp limits dasatinib CNS penetration, affecting ALL treatment efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206811" }, { "confidence": "medium", "disease": "Chronic Myeloid Leukemia (CML)", "glycan_involvement": "Glycosylation affects CYP3A4 stability and activity.", "mechanism": "CYP3A4 metabolizes dasatinib, influencing drug clearance and efficacy in CML.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206811" }, { "confidence": "low", "disease": "Nephrotic Syndrome", "glycan_involvement": "Glycosylation modulates P-gp renal localization and function.", "mechanism": "Dasatinib-induced nephrotic syndrome may involve altered P-gp-mediated drug transport in renal tissue.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC11206811" }, { "confidence": "low", "disease": "Hepatitis B Virus Reactivation", "glycan_involvement": "Glycosylation impacts P-gp immune cell function.", "mechanism": "Dasatinib therapy may trigger HBV reactivation, possibly via immune modulation and altered drug transport.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC11206811" }, { "confidence": "low", "disease": "Interstitial Lung Disease", "glycan_involvement": "Glycosylation affects P-gp expression in lung epithelium.", "mechanism": "Dasatinib-associated pulmonary toxicity may be influenced by P-gp-mediated drug efflux in lung tissue.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC11206811" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Obesity may affect glycosylation patterns of P-gp, impacting pharmacokinetics.", "mechanism": "Obesity alters drug absorption and distribution, possibly via changes in P-gp expression and function.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker", "source_pmcid": "PMC11206811" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Obesity can influence glycosylation of CYP3A4, affecting enzyme activity.", "mechanism": "Obesity may modulate CYP3A4 activity, altering dasatinib metabolism.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "biomarker", "source_pmcid": "PMC11206811" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Obesity may alter BCRP glycosylation, modifying transporter function.", "mechanism": "Obesity may impact BCRP-mediated drug transport, affecting dasatinib pharmacokinetics.", "protein": "Breast Cancer Resistance Protein (BCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206811" }, { "confidence": "high", "disease": "Inflammatory muscle diseases", "glycan_involvement": "Glycosylation affects IL-6 stability and receptor binding.", "mechanism": "IL-6 is elevated in muscle inflammation and damage; reduction indicates decreased inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206817" }, { "confidence": "high", "disease": "Inflammatory muscle diseases", "glycan_involvement": "CK glycosylation may affect serum stability.", "mechanism": "CK is released during muscle damage; lower levels after probiotic intervention indicate protection.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206817" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Degrades mucin glycoproteins, modulating gut barrier and metabolism.", "mechanism": "Increased abundance correlates with reduced obesity risk and improved metabolic health.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Outer membrane glycoproteins may interact with host immunity.", "mechanism": "Higher Sutterella abundance is associated with increased IBD risk.", "protein": "Sutterella spp.", "relationship_type": "causal", "source_pmcid": "PMC11206817" }, { "confidence": "high", "disease": "Inflammatory muscle diseases", "glycan_involvement": "Fermentation of dietary glycans to SCFAs.", "mechanism": "Butyrate production reduces inflammation and supports muscle mass.", "protein": "Lachnospiraceae (butyrate producers)", "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Ferments complex glycans to SCFAs.", "mechanism": "Increased abundance linked to reduced cardiovascular risk in obesity.", "protein": "Ruminococcus spp.", "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Degrades dietary glycans, influencing host metabolism.", "mechanism": "Higher abundance associated with reduced visceral fat and improved metabolic profile.", "protein": "Prevotella copri", "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Mucin glycan degradation modulates gut barrier and glucose homeostasis.", "mechanism": "Depletion linked to diabetes; increased abundance improves glucose metabolism.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Mucin glycan degradation affects liver-gut axis.", "mechanism": "Higher levels associated with reduced liver fat and inflammation.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC11206817" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates IL-6 activity and immune signaling.", "mechanism": "IL-6 is elevated in asthma-related inflammation; reduction indicates improved airway health.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206817" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates host interaction.", "mechanism": "Spike S1 binds ACE2, triggers immune activation and inflammation.", "protein": "SARS-CoV-2 Spike Glycoprotein S1", "relationship_type": "causal", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "ARDS", "glycan_involvement": "Glycosylation affects immune recognition and pathogenicity.", "mechanism": "Induces cytokine storm and lung cell inflammation via NLRP3 inflammasome.", "protein": "SARS-CoV-2 Spike Glycoprotein S1", "relationship_type": "causal", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation reported in this study.", "mechanism": "Activation leads to inflammasome formation, driving cytokine release and hyperinflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206841" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "ASC bridges NLRP3 and caspase-1, facilitating inflammasome assembly and cytokine maturation.", "protein": "ASC (PYCARD)", "protein_enriched": { "function": "Functions as a key mediator in apoptosis and inflammation (PubMed:11103777, PubMed:12646168, PubMed:15030775, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMe", "gene_name": "PYCARD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ULZ3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206841" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Caspase-1 activation cleaves pro-IL-1\u03b2 and pro-IL-18, promoting inflammation.", "protein": "Caspase-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and stability.", "mechanism": "Elevated IL-6 correlates with disease severity and cytokine storm.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-1\u03b2 is glycosylated, modulating activity.", "mechanism": "Increased IL-1\u03b2 reflects inflammasome activation and inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-18 is glycosylated, influencing function.", "mechanism": "Elevated IL-18 indicates inflammasome-driven inflammation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206841" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates Spike binding and viral entry.", "mechanism": "ACE2 is the entry receptor for Spike S1, facilitating viral infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11206841" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "Glycosylation may affect persistence and immune evasion.", "mechanism": "Persistent Spike S1-induced inflammation may contribute to post-acute sequelae.", "protein": "SARS-CoV-2 Spike Glycoprotein S1", "relationship_type": "causal", "source_pmcid": "PMC11206841" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for IR function and cell surface expression.", "mechanism": "Vanadium complex may activate IR signaling, improving insulin sensitivity.", "protein": "Insulin receptor (IR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206843" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects IRS-1 stability and signaling.", "mechanism": "Vanadium complexes modulate IRS-1 expression, enhancing insulin signaling.", "protein": "Insulin receptor substrate 1 (IRS-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206843" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation critical for GLUT4 trafficking.", "mechanism": "Vanadium complexes increase GLUT4 translocation, improving glucose uptake.", "protein": "Glucose transporter 4 (GLUT4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206843" }, { "confidence": "medium", "disease": "Glucocorticoid-induced metabolic syndrome", "glycan_involvement": "Glycosylation modulates GR localization and activity.", "mechanism": "DEXA activates GR, leading to insulin resistance and metabolic disturbances.", "protein": "Glucocorticoid receptor (GR)", "protein_enriched": { "function": "Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mi", "gene_name": "NR3C1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P04150" }, "relationship_type": "causal", "source_pmcid": "PMC11206843" }, { "confidence": "medium", "disease": "Glucocorticoid-induced metabolic syndrome", "glycan_involvement": "Glycosylation affects enzyme stability and tissue distribution.", "mechanism": "11\u03b2-HSD-1 increases local GC activation, promoting IR and obesity.", "protein": "11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD-1)", "protein_enriched": { "function": "Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H) (PubMed:10497248, Pub", "gene_name": "HSD11B1", "glycan_count": 6, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G64527OM", "G25451PN", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR" ], "uniprot_id": "P28845" }, "relationship_type": "causal", "source_pmcid": "PMC11206843" }, { "confidence": "low", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation modulates GS activity.", "mechanism": "GCs and insulin regulate GS activity, affecting hepatic glycogen storage.", "protein": "Glycogen synthase (GS)", "protein_enriched": { "function": "Glycogen synthase participates in the glycogen biosynthetic process along with glycogenin and glycogen branching enzyme. Extends the primer composed of a few glucose units formed by glycogenin by addi", "gene_name": "GYS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13807" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206843" }, { "confidence": "low", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation influences GP function.", "mechanism": "GCs inhibit GP, increasing glycogen storage and contributing to hyperglycemia.", "protein": "Glycogen phosphorylase (GP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206843" }, { "confidence": "high", "disease": "Advanced glycation end-product (AGE)-related complications", "glycan_involvement": "Non-enzymatic glycation of serum glycoproteins.", "mechanism": "Elevated fructosamine reflects increased glycation due to hyperglycemia.", "protein": "Fructosamine (glycated serum proteins)", "relationship_type": "biomarker", "source_pmcid": "PMC11206843" }, { "confidence": "low", "disease": "Glucose intolerance", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "GCs upregulate PEPCK, increasing gluconeogenesis and glucose intolerance.", "protein": "Phosphoenolpyruvate carboxykinase (PEPCK)", "protein_enriched": { "function": "Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway (PubMed:3086869). Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamin", "gene_name": "Pfas", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35421" }, "relationship_type": "causal", "source_pmcid": "PMC11206843" }, { "confidence": "low", "disease": "Glucose intolerance", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "GCs upregulate G6P, increasing hepatic glucose output.", "protein": "Glucose-6-phosphatase (G6P)", "relationship_type": "causal", "source_pmcid": "PMC11206843" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects COX-2 stability and activity.", "mechanism": "Curcuminoids inhibit COX-2, reducing prostaglandin E2 and inflammatory response.", "protein": "COX-2 (Cyclooxygenase-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206846" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates NF-kB pathway components.", "mechanism": "DMC and BDMC inhibit LPS-induced NF-kB activation, reducing inflammatory signaling.", "protein": "NF-kB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206846" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "ALT is a glycoprotein; glycosylation affects serum stability.", "mechanism": "Elevated ALT indicates hepatic cellular damage in diabetes; curcuminoids lower ALT.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206846" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "AST glycosylation affects its serum half-life.", "mechanism": "Elevated AST indicates liver injury in diabetes; curcuminoids lower AST.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11206846" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation essential for \u03b1-glucosidase activity.", "mechanism": "BDMC, curcumin, and DMC inhibit \u03b1-glucosidase, reducing glucose absorption.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206846" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation required for enzyme function.", "mechanism": "Curcuminoids inhibit \u03b1-amylase, decreasing carbohydrate digestion.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206846" }, { "confidence": "medium", "disease": "Wound healing impairment", "glycan_involvement": "Collagen glycosylation affects fibril formation and tissue repair.", "mechanism": "Curcuminoids promote collagen synthesis, accelerating wound closure.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206846" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Turmeric oil inhibits prostaglandin E2 synthesis, reducing inflammation.", "protein": "Prostaglandin E2 synthase", "protein_enriched": { "function": "Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic r", "gene_name": "PTGES3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15185" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206846" }, { "confidence": "high", "disease": "Edema", "glycan_involvement": "Glycosylation affects COX-2 localization and function.", "mechanism": "COX-2-mediated prostaglandin production drives carrageenan-induced edema; curcuminoids inhibit this.", "protein": "COX-2 (Cyclooxygenase-2)", "relationship_type": "causal", "source_pmcid": "PMC11206846" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Altered glycosylation in diabetes impairs collagen function; curcuminoids may restore normal glycosylation.", "mechanism": "Curcuminoids improve tissue remodeling and collagen deposition in diabetic wounds.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206846" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "LBP is glycosylated, which affects its stability and binding to LPS.", "mechanism": "LBP levels increase with bacterial translocation and gut permeability, reflecting severity of fibrosis in MASLD.", "protein": "Lipopolysaccharide-binding protein (LBP)", "protein_enriched": { "function": "Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:2412035", "gene_name": "LBP", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G84452RH", "G94470IW" ], "uniprot_id": "P18428" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "I-FABP is glycosylated, influencing its secretion and stability.", "mechanism": "Elevated plasma I-FABP indicates increased gut epithelial permeability, correlating with advanced fibrosis.", "protein": "Intestinal fatty acid binding protein (I-FABP)", "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect PNPLA3 localization and function, but specific sites not detailed.", "mechanism": "PNPLA3 rs738409 GG genotype increases risk of advanced fibrosis via impaired triglyceride metabolism and hepatic stellate cell activation.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Potential impact on protein stability and cell surface expression.", "mechanism": "PNPLA3 variant (Ile148Met) leads to triglyceride retention in hepatocytes, promoting MASLD progression.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates LBP's affinity for LPS.", "mechanism": "LBP reflects endotoxin exposure and gut-liver axis activation in MASLD.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects I-FABP release into circulation.", "mechanism": "I-FABP levels indicate gut barrier dysfunction in MASLD.", "protein": "I-FABP", "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "IL-6 glycosylation influences receptor binding and stability.", "mechanism": "IL-6 levels trend higher in advanced fibrosis, reflecting inflammatory activity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and bioactivity.", "mechanism": "TNF-\u03b1 levels trend higher in advanced fibrosis, indicating inflammation.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "medium", "disease": "Steatohepatitis", "glycan_involvement": "Glycosylation modulates LBP's function.", "mechanism": "LBP increases with endotoxin exposure, correlating with liver inflammation.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC11206871" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Possible impact on protein function, not detailed.", "mechanism": "PNPLA3 variant increases risk for HCC via chronic liver injury and fibrosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC11206871" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and serum half-life.", "mechanism": "Serum albumin levels decrease with worsening liver function in MAFLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion and stability.", "mechanism": "ALT levels increase in serum with hepatocyte injury in MAFLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "AST is glycosylated; glycosylation may affect its serum detection.", "mechanism": "AST levels increase in serum with liver cell damage in MAFLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "DILI", "glycan_involvement": "Altered glycosylation may reflect liver injury.", "mechanism": "Decreased serum albumin indicates impaired liver synthetic function in DILI.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "DILI", "glycan_involvement": "Glycosylation status may change with liver injury.", "mechanism": "ALT elevation is a hallmark of hepatocellular injury in DILI.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "HILI", "glycan_involvement": "Glycosylation changes may occur in HILI.", "mechanism": "Reduced albumin levels indicate liver dysfunction in herb-induced injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "HILI", "glycan_involvement": "Potential for altered glycosylation with injury.", "mechanism": "ALT is elevated in serum during HILI.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "N-glycosylation may be altered in chronic liver disease.", "mechanism": "Serum albumin reduction reflects advanced NAFLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Albumin glycosylation may affect bilirubin binding.", "mechanism": "Increased serum bilirubin (bound to albumin) indicates impaired hepatic clearance.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Non-enzymatic glycation and altered N-glycosylation.", "mechanism": "Albumin glycation and glycosylation are altered in T2DM, reflecting metabolic dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206875" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "CRP is elevated in sepsis and reflects systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "LPC is a glycophospholipid; glycan headgroup composition may affect immune signaling.", "mechanism": "LPC levels are downregulated in sepsis, reflecting altered lipid metabolism.", "protein": "Lysophosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "SM is a glycosphingolipid; glycan moiety may modulate cell signaling.", "mechanism": "SM levels decrease in sepsis, indicating membrane remodeling and cell stress.", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "PC is a glycophospholipid; glycan structure may affect function.", "mechanism": "PC levels are altered (up or down) in sepsis, reflecting changes in membrane composition.", "protein": "Phosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates ApoA1 function and HDL interaction.", "mechanism": "ApoA1 is associated with HDL and anti-inflammatory effects; altered in infection/inflammation.", "protein": "Apolipoprotein A1", "relationship_type": "protective", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosphingolipid; glycan chain length/structure may affect signaling.", "mechanism": "Downregulation associated with increased risk after early-life infection.", "protein": "Trihexosylceramide", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosphingolipid; glycan moiety may influence immune recognition.", "mechanism": "Levels change during anti-TB therapy; potential TDM marker.", "protein": "Dihexosylceramide", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Ether-linked phospholipid; glycan structure may affect antioxidant properties.", "mechanism": "Levels decrease with inflammation and infection.", "protein": "Plasmalogen", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "HDL contains glycoproteins; glycosylation affects function.", "mechanism": "HDL levels and composition (including glycoproteins) are altered after infection, affecting risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206893" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycophospholipid; glycan headgroup may modulate immune response.", "mechanism": "PE levels change in sepsis and infection, reflecting membrane and metabolic alterations.", "protein": "Phosphatidylethanolamine", "relationship_type": "biomarker", "source_pmcid": "PMC11206893" }, { "confidence": "high", "disease": "PNALD", "glycan_involvement": "PC is a major membrane phospholipid with glycan headgroup; its synthesis and turnover are glycan-dependent.", "mechanism": "Choline deficiency impairs PC synthesis, leading to liver steatosis and dysfunction during TPN.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "causal", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "PNALD", "glycan_involvement": "SPH contains choline headgroup; glycosylation affects membrane stability.", "mechanism": "SPH synthesis from PC is required to convert pro-apoptotic ceramides; deficiency leads to liver pathology.", "protein": "Sphingomyelin (SPH)", "relationship_type": "causal", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "Hepatic Steatosis", "glycan_involvement": "VLDL is a glycoprotein; glycosylation affects lipid transport.", "mechanism": "Impaired PC synthesis reduces VLDL secretion, causing hepatic lipid accumulation.", "protein": "VLDL", "relationship_type": "causal", "source_pmcid": "PMC11206924" }, { "confidence": "medium", "disease": "PNALD", "glycan_involvement": "Ceramide is a sphingolipid precursor; glycosylation regulates its conversion.", "mechanism": "Failure to convert ceramide to SPH (due to low PC) increases apoptosis and liver injury.", "protein": "Ceramide", "relationship_type": "causal", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "PNALD", "glycan_involvement": "PEMT is a glycoprotein; glycosylation may affect enzyme stability.", "mechanism": "Low PEMT activity in infants limits endogenous PC synthesis, increasing risk of liver disease during TPN.", "protein": "PEMT", "relationship_type": "causal", "source_pmcid": "PMC11206924" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "PPAR\u03b1 is glycosylated; glycan status may affect transcriptional activity.", "mechanism": "Choline deficiency increases PPAR\u03b1 promoter methylation, altering lipid metabolism.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "PNALD", "glycan_involvement": "ALT is glycosylated; glycosylation affects secretion and stability.", "mechanism": "ALT levels rise with choline deficiency and liver injury; inversely correlated with plasma choline.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "PNALD", "glycan_involvement": "AST is glycosylated; glycosylation affects function.", "mechanism": "AST levels increase with liver damage due to choline deficiency.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11206924" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Alkaline phosphatase is heavily glycosylated; glycan status affects activity.", "mechanism": "Elevated in cholestasis associated with choline deficiency during TPN.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206924" }, { "confidence": "medium", "disease": "Cognitive Impairment", "glycan_involvement": "SAM-dependent methylation affects glycoprotein biosynthesis and epigenetics.", "mechanism": "Choline-derived betaine supports SAM synthesis for methylation, DNA repair, and neurological function.", "protein": "S-adenosylmethionine (SAM)", "relationship_type": "protective", "source_pmcid": "PMC11206924" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates C3 binding to exosome surfaces, affecting recognition and clearance.", "mechanism": "Protein corona formation on exosomes alters exosome-cell interactions, impacting tumor progression and immune evasion.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Fc glycosylation affects IgG binding and immune response.", "mechanism": "IgG in exosome protein corona influences exosome uptake in neural tissues, potentially modulating neuroinflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "high", "disease": "Wound healing", "glycan_involvement": "Glycosylation regulates fibronectin structure and cell interaction.", "mechanism": "Fibronectin-enriched exosome corona promotes cell adhesion and migration, enhancing tissue repair.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206934" }, { "confidence": "medium", "disease": "Immune diseases", "glycan_involvement": "Glycosylation critical for Factor H function and exosome binding.", "mechanism": "Factor H in exosome corona regulates complement activation, reducing immune-mediated damage.", "protein": "Complement Factor H", "relationship_type": "protective", "source_pmcid": "PMC11206934" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects antithrombin activity and exosome association.", "mechanism": "Antithrombin III in exosome corona modulates coagulation and inflammatory responses.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "MHC glycosylation influences peptide presentation and immune activation.", "mechanism": "Exosomal MHC-peptide complexes stimulate antigen-specific T cell responses for cancer immunotherapy.", "protein": "Major Histocompatibility Complex (MHC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206934" }, { "confidence": "medium", "disease": "Angiogenesis-related disorders", "glycan_involvement": "Glycosylation affects ApoA1 structure and exosome binding.", "mechanism": "Exosome-lipoprotein complexes modulate vascular cell interactions, impacting angiogenesis.", "protein": "Apolipoprotein A1", "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "high", "disease": "Wound healing", "glycan_involvement": "VEGF glycosylation modulates receptor binding and activity.", "mechanism": "Exosomal VEGF activates angiogenesis pathways, promoting tissue regeneration.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206934" }, { "confidence": "low", "disease": "Infection", "glycan_involvement": "Glycosylation impacts Factor V stability and exosome interaction.", "mechanism": "Factor V in exosome corona may influence coagulation and immune response during infection.", "protein": "Factor V", "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "Albumin glycosylation modulates exosome binding and circulation time.", "mechanism": "Albumin in exosome corona affects exosome stability and delivery of therapeutic miRNAs to joint tissues.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206934" }, { "confidence": "medium", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Regulates glucose and lipid metabolism; low levels associated with MetS.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor binding and stability.", "mechanism": "Controls appetite and energy expenditure; resistance and altered glycosylation linked to obesity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "Reflects chronic hyperglycemia; increased in T2D and MetS.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates LDL receptor interaction.", "mechanism": "Elevated LDL promotes plaque formation; glycoprotein components mediate uptake.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC11206952" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation affects anti-atherogenic properties.", "mechanism": "HDL removes cholesterol from arteries; glycoprotein structure essential for function.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11206952" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation influences enzyme activity and inhibitor binding.", "mechanism": "ACE regulates blood pressure; inhibitors used in hypertension.", "protein": "Angiotensin-Converting Enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206952" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation affects stability and receptor interaction.", "mechanism": "Insulin regulates glucose uptake; resistance and altered glycosylation in T2D.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206952" }, { "confidence": "low", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation modulates enzyme stability.", "mechanism": "Elevated AST indicates liver injury; glycoprotein enzyme.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "low", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Elevated ALT signals liver dysfunction in MetS.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "low", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "TSH regulates metabolism; altered levels may contribute to MetS.", "protein": "Thyroid-Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11206952" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects PAI-1 stability and secretion.", "mechanism": "PAI-1 is upregulated in obesity, contributing to glucose intolerance, insulin resistance, and atherosclerosis.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for leptin secretion and receptor interaction.", "mechanism": "Leptin levels correlate with adiposity; dysregulation leads to impaired energy homeostasis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates resistin's activity and stability.", "mechanism": "Resistin promotes inflammation and insulin resistance via cytokine induction.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 induces PAI-1 and promotes inflammation and insulin resistance in adipose tissue.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for MCP-1 chemotactic activity.", "mechanism": "MCP-1 recruits macrophages to adipose tissue, driving inflammation and insulin resistance.", "protein": "MCP-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation essential for multimerization and bioactivity.", "mechanism": "Adiponectin improves insulin sensitivity and reduces inflammation; low levels are linked to diabetes risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects GLUT4 trafficking and function.", "mechanism": "GLUT4 mediates insulin-stimulated glucose uptake; downregulation leads to insulin resistance.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11206994" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect STAMP2 localization and function.", "mechanism": "STAMP2 is upregulated in obesity and linked to oxidative stress and inflammation in adipose tissue.", "protein": "STAMP2", "protein_enriched": { "function": "Highly specific for ethanolamine phosphorylation. May be a rate-controlling step in phosphatidylethanolamine biosynthesis", "gene_name": "ETNK1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G83460ZZ" ], "uniprot_id": "Q9HBU6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206994" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for F4/80 cell surface expression.", "mechanism": "F4/80 marks macrophage infiltration in adipose tissue, indicating inflammation.", "protein": "F4/80", "protein_enriched": { "function": "May have regulatory role in cell division or differentiation in response to extracellular signals", "gene_name": "Skil", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q60665" }, "relationship_type": "biomarker", "source_pmcid": "PMC11206994" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b2 secretion and receptor binding.", "mechanism": "TGF-\u03b2 upregulates PAI-1, contributing to vascular pathology in obesity.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC11206994" }, { "confidence": "high", "disease": "Non-small cell lung carcinoma (NSCLC)", "glycan_involvement": "N-glycosylation of PD-L1 is critical for PD-1 interaction and protein stability.", "mechanism": "PD-L1 on tumor cells binds PD-1 on T cells, suppressing immune response; blockade with nivolumab restores antitumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "N-glycosylation modulates PD-L1 stability and immune checkpoint function.", "mechanism": "PD-L1 expression enables immune evasion; anti-PD-1/PD-L1 therapy (nivolumab) effective in advanced melanoma.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "CTLA-4 is a glycoprotein; glycosylation affects surface expression and function.", "mechanism": "CTLA-4 inhibits T cell activation; ipilimumab blocks CTLA-4, enhancing antitumor T cell response.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "high", "disease": "Renal cell carcinoma", "glycan_involvement": "PD-1 is glycosylated, which may affect ligand binding.", "mechanism": "PD-1 on T cells mediates immune suppression; nivolumab blocks PD-1, improving survival.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation regulates CTLA-4 trafficking and function.", "mechanism": "CTLA-4 hypofunction leads to loss of immune homeostasis and autoimmunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC11207028" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "BTLA is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "BTLA deficiency increases T cell proliferation and autoimmunity.", "protein": "BTLA", "relationship_type": "causal/protective", "source_pmcid": "PMC11207028" }, { "confidence": "high", "disease": "Microsatellite instability-high/dMMR colorectal cancer", "glycan_involvement": "N-glycosylation of PD-L1 is required for effective immune checkpoint function.", "mechanism": "High PD-L1 expression in MSI-H/dMMR tumors predicts response to PD-1/PD-L1 blockade.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "B7x is a glycoprotein; glycosylation may affect immune interactions.", "mechanism": "B7x acts as an inhibitory ligand for BTLA, suppressing T cell responses; targeting B7x/BTLA may enhance immunotherapy.", "protein": "B7x (VTCN1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances immune suppression.", "mechanism": "PD-L1 expression on tumor cells mediates immune evasion; anti-PD-1/PD-L1 therapy shows efficacy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207028" }, { "confidence": "medium", "disease": "Sweet\u2019s syndrome", "glycan_involvement": "CTLA-4 glycosylation may influence immune regulation and adverse event risk.", "mechanism": "Ipilimumab-induced CTLA-4 blockade can trigger Sweet\u2019s syndrome as an immune-related adverse event.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal (adverse effect)", "source_pmcid": "PMC11207028" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "O-glycosylation stabilizes GLP-1 and modulates its activity.", "mechanism": "Allulose increases GLP-1, enhancing glucose regulation and improving glycemic control.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207032" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "O-glycosylation affects GLP-1 secretion and half-life.", "mechanism": "Elevated GLP-1 reduces appetite and body weight; allulose increases GLP-1.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Insulin glycosylation affects secretion and receptor interaction.", "mechanism": "Allulose reduces hyperinsulinemia and improves insulin sensitivity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation is essential for adiponectin multimerization and function.", "mechanism": "Allulose prevents reduction of adiponectin seen in obesity, supporting metabolic health.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation modulates secretion and receptor binding.", "mechanism": "Leptin levels increase with obesity; allulose blunts this effect.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP is elevated in metabolic inflammation; allulose reduces CRP levels.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "O-glycosylation required for adiponectin bioactivity.", "mechanism": "Higher adiponectin is associated with improved insulin sensitivity; allulose maintains adiponectin levels.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11207032" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "O-glycosylation modulates GLP-1 function.", "mechanism": "GLP-1 improves insulin sensitivity; allulose increases GLP-1.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207032" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation influences CRP hepatic clearance.", "mechanism": "CRP is elevated in NAFLD; allulose reduces CRP, indicating reduced hepatic inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207032" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects leptin signaling.", "mechanism": "Leptin correlates with adiposity and insulin resistance; allulose reduces leptin.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207032" }, { "confidence": "high", "disease": "Taste disorders (TDs)", "glycan_involvement": "Glycosylation is essential for miraculin's taste-modifying activity.", "mechanism": "Miraculin binds sweet taste receptors, modifying taste perception and improving taste acuity in patients with TDs.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "high", "disease": "Dysgeusia", "glycan_involvement": "Glycosylation required for receptor interaction.", "mechanism": "Miraculin improves altered taste perception (dysgeusia) in cancer patients undergoing chemotherapy/radiotherapy.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "high", "disease": "Malnutrition in cancer", "glycan_involvement": "Glycosylation maintains miraculin's stability and function.", "mechanism": "Improved taste perception leads to increased food intake, better energy balance, and improved nutritional status.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "medium", "disease": "Constipation", "glycan_involvement": "Glycosylation required for bioactivity.", "mechanism": "Improved nutritional intake and quality of life, including reduction in constipation symptoms.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "medium", "disease": "Fatigue", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Improved nutritional status and energy intake reduce fatigue in cancer patients.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "high", "disease": "Chemotherapy-induced taste disorder", "glycan_involvement": "Glycosylation critical for receptor binding.", "mechanism": "Miraculin counteracts chemotherapy-induced taste alterations by modifying sweet receptor response.", "protein": "Miraculin", "protein_enriched": { "function": "Sulfur-rich seed storage protein that remains undegraded at germination (PubMed:11406286). The uncleaved form exhibits some inhibitory activity against GH11 xylanase from T.longibrachiatum, more at pH", "gene_name": "Cgamma", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9FSH9" }, "relationship_type": "protective", "source_pmcid": "PMC11207068" }, { "confidence": "medium", "disease": "Malnutrition in cancer", "glycan_involvement": "RBP is a glycoprotein; glycosylation affects stability and serum half-life.", "mechanism": "RBP levels reflect changes in nutritional status during intervention.", "protein": "Retinol-binding protein (RBP)", "protein_enriched": { "function": "Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans ret", "gene_name": "RBP4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02753" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207068" }, { "confidence": "high", "disease": "Prostate carcinoma", "glycan_involvement": "MMP-2 is a glycoprotein; glycosylation affects its secretion and activity.", "mechanism": "Cranberry triterpenoids (e.g., ursolic acid) inhibit MMP-2 expression, reducing tumor invasion and metastasis.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "high", "disease": "Prostate carcinoma", "glycan_involvement": "MMP-9 is a glycoprotein; glycosylation modulates its function.", "mechanism": "Cranberry triterpenoids and polyphenols inhibit MMP-9 expression, limiting cancer cell migration.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "medium", "disease": "Renal carcinoma", "glycan_involvement": "MMP-2 glycosylation is important for its activity.", "mechanism": "Ursolic acid from cranberry inhibits MMP-2, reducing renal cancer cell migration and tubule formation.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "medium", "disease": "Renal carcinoma", "glycan_involvement": "MMP-9 glycosylation affects secretion and stability.", "mechanism": "Cranberry triterpenoids may inhibit MMP-9, reducing metastatic potential.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "medium", "disease": "Prostate carcinoma", "glycan_involvement": "VEGF is a glycoprotein; glycosylation is critical for receptor binding.", "mechanism": "Cranberry anthocyanins inhibit VEGF induction, potentially limiting angiogenesis in tumors.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "low", "disease": "Bacterial infection (general)", "glycan_involvement": "Glycosylation affects MMP-2's role in tissue remodeling during infection.", "mechanism": "MMP-2 may be upregulated in infection/inflammation; cranberry compounds may modulate this.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207080" }, { "confidence": "low", "disease": "Bacterial infection (general)", "glycan_involvement": "Glycosylation modulates MMP-9's inflammatory activity.", "mechanism": "MMP-9 is involved in inflammation; cranberry polyphenols may reduce its expression.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207080" }, { "confidence": "low", "disease": "Renal carcinoma", "glycan_involvement": "VEGF glycosylation is essential for its pro-angiogenic function.", "mechanism": "Cranberry anthocyanins may reduce VEGF-mediated angiogenesis in renal cancer.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207080" }, { "confidence": "low", "disease": "Urinary tract infection", "glycan_involvement": "Glycosylation affects MMP-2's function in infection.", "mechanism": "MMP-2 may be involved in tissue remodeling during infection; cranberry PACs may indirectly modulate this.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207080" }, { "confidence": "low", "disease": "Urinary tract infection", "glycan_involvement": "Glycosylation modulates MMP-9's inflammatory role.", "mechanism": "MMP-9 is involved in inflammation; cranberry PACs may reduce its expression.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207080" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CD47 is a glycoprotein; glycosylation may affect its interaction with SIRP\u03b1 and immune cells.", "mechanism": "CD47 on exosomes provides anti-phagocytosis signal, potentially increasing exosome half-life and modulating immune evasion in cancer therapy.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207238" }, { "confidence": "high", "disease": "Neurological conditions", "glycan_involvement": "Transferrin is N-glycosylated, which is critical for receptor binding and BBB transcytosis.", "mechanism": "Transferrin modification of exosomes enhances blood-brain barrier crossing for drug delivery in neurological diseases.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Neurological conditions", "glycan_involvement": "NCAM is polysialylated; glycosylation modulates cell adhesion and targeting.", "mechanism": "NCAM modification enhances neuron targeting of exosomes for potential therapy in neurological diseases.", "protein": "NCAM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CD9 is a glycoprotein; glycosylation may influence exosome formation and cell interaction.", "mechanism": "CD9 is enriched in exosomes and is implicated in tumor progression and metastasis.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CD63 is glycosylated, which may affect exosome biogenesis.", "mechanism": "CD63 is a canonical exosome marker, often upregulated in tumor-derived exosomes.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "CD81 is glycosylated; glycosylation may affect viral interactions.", "mechanism": "CD81 is involved in viral entry and immune modulation via exosomes.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "ICAM1 is heavily N-glycosylated, influencing cell-cell interactions.", "mechanism": "ICAM1 on exosomes mediates immune cell adhesion and trafficking in inflammatory diseases.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "EpCAM is glycosylated; glycosylation affects cell adhesion and immune recognition.", "mechanism": "EpCAM is present on exosomes from epithelial tumors, serving as a diagnostic marker.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "medium", "disease": "Hereditary disorders", "glycan_involvement": "Transferrin receptor is N-glycosylated, essential for ligand binding.", "mechanism": "Exosome targeting via transferrin receptor can facilitate delivery in genetic diseases affecting the CNS.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207238" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "ALIX is involved in exosome biogenesis and is upregulated in tumor exosomes.", "protein": "ALIX", "relationship_type": "biomarker", "source_pmcid": "PMC11207238" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Insulin is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Psidium guajava and Seriphium plumosum phytochemicals stimulate insulin secretion and enhance insulin sensitivity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "Psidium guajava leaf extract lowers glycosylated hemoglobin (HbA1c) in diabetic rats.", "protein": "Hemoglobin A1c (glycated hemoglobin)", "relationship_type": "biomarker", "source_pmcid": "PMC11207340" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "GLUT4 is glycosylated, which affects its trafficking and function.", "mechanism": "Plant extracts improve GLUT4 expression, enhancing glucose uptake in adipocytes.", "protein": "GLUT4 (Glucose transporter type 4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Alpha-amylase is glycosylated, influencing enzyme activity.", "mechanism": "Phytochemicals inhibit alpha-amylase, reducing carbohydrate digestion and postprandial glucose spikes.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Alpha-glucosidase glycosylation affects its stability and activity.", "mechanism": "Plant extracts inhibit alpha-glucosidase, decreasing intestinal glucose absorption.", "protein": "Alpha-glucosidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "GLP-1 is glycosylated, impacting its half-life and receptor interaction.", "mechanism": "Psidium guajava may enhance incretin-based therapy, preserving beta cell function.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "low", "disease": "Insulin Resistance", "glycan_involvement": "PDK1 glycosylation modulates kinase activity.", "mechanism": "Plant extracts counter reduction in PDK1 expression, improving insulin signaling.", "protein": "PDK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207340" }, { "confidence": "low", "disease": "Beta Cell Dysfunction", "glycan_involvement": "Caspase 3 glycosylation may affect apoptotic activity.", "mechanism": "Combined herbal extracts reduce caspase 3 expression, protecting beta cells from apoptosis.", "protein": "Caspase 3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11207340" }, { "confidence": "low", "disease": "Diabetic Inflammation", "glycan_involvement": "IL-1\u03b2 glycosylation influences cytokine secretion and activity.", "mechanism": "IL-1\u03b2 induces beta cell apoptosis; plant extracts reduce its inflammatory effects.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC11207340" }, { "confidence": "low", "disease": "Diabetic Inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects receptor binding and signaling.", "mechanism": "TNF-\u03b1 promotes insulin resistance and inflammation; plant extracts have anti-inflammatory effects.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC11207340" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "CD44 is a glycoprotein receptor for HA; glycosylation mediates ligand binding.", "mechanism": "CD44 is overexpressed on TNBC cells and targeted by hyaluronic acid or chitosan oligosaccharide for drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "Nectin-4 is a glycoprotein; glycosylation may affect stability and cell surface expression.", "mechanism": "Nectin-4 is expressed in 62% of TNBC and associated with poor prognosis; targeted by monoclonal antibodies for imaging and therapy.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "PD-L1 is glycosylated; glycosylation modulates immune recognition.", "mechanism": "PD-L1 is highly expressed in TNBC, used for immune checkpoint blockade therapy and as a marker for immunotherapy response.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "ICAM1 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "ICAM1 is targeted by antibody-drug conjugates for selective cytotoxicity in TNBC.", "protein": "ICAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "gpNMB is a glycoprotein; glycosylation may affect antibody recognition.", "mechanism": "gpNMB is overexpressed in TNBC, correlates with recurrence/metastasis, and is targeted by antibody-drug conjugates (CDX-011).", "protein": "gpNMB", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "EGFR is N-glycosylated; glycosylation modulates ligand binding and receptor function.", "mechanism": "EGFR is overexpressed in ~60% of TNBC, associated with poor prognosis, and targeted by aptamers and nanocarriers.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation affects matrix interactions.", "mechanism": "Fibronectin is a tumor microenvironment marker in TNBC, targeted for imaging and photodynamic therapy.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "uPAR is glycosylated; glycosylation affects cell surface localization.", "mechanism": "uPAR is targeted by NIR-labeled nanocarriers for imaging and drug delivery in TNBC.", "protein": "uPAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "CD82 is a glycoprotein; glycosylation may affect exosome incorporation.", "mechanism": "CD82 overexpression in exosome-mimetic nanovesicles inhibits TNBC cell migration and metastasis.", "protein": "CD82", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling (PubMed:19497983). Participat", "gene_name": "CD82", "glycan_count": 13, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G11115RO", "G53075ES", "G66537LK", "G70232NH", "G94665LC", "G31852PQ", "G45395BF", "G62765YT", "G64527OM", "G70101JE", "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P27701" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "medium", "disease": "Triple-Negative Breast Cancer", "glycan_involvement": "Sortilin is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "SORT1 is highly expressed in TNBC and targeted by peptides for drug delivery.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207493" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "O-glycosylation of MUC2 VNTRs is critical for hydration and expansion; impaired ion exchange prevents proper glycan-mediated swelling.", "mechanism": "Dysfunctional CFTR impairs bicarbonate secretion, preventing MUC2 mucin unfolding and detachment, resulting in thick, adherent mucus in the small intestine.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Decreased sulfation of O-glycans in VNTR region reduces negative charge and barrier function.", "mechanism": "Reduced MUC2 glycan sulfation observed in ulcerative colitis patients, leading to increased mucus penetrability and inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Chronic rhinosinusitis", "glycan_involvement": "O-glycosylation (VNTR region) likely modulates mucin properties and inflammatory response.", "mechanism": "MUC8 is upregulated in airway epithelium of patients with chronic rhinosinusitis.", "protein": "MUC8", "relationship_type": "biomarker", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "O-glycosylation modulates mucin function in mucus viscosity.", "mechanism": "MUC8 is upregulated in airways of cystic fibrosis patients, possibly as a compensatory or inflammatory response.", "protein": "MUC8", "relationship_type": "biomarker", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Small intestinal bacterial overgrowth (SIBO)", "glycan_involvement": "O-glycosylation required for proper mucus expansion and barrier function.", "mechanism": "Impaired MUC2 mucus detachment in CF leads to thick mucus, promoting SIBO.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11207715" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "Glycosylation status affects MUC2 folding and accessibility to protease cleavage.", "mechanism": "Lack of meprin \u03b2-mediated cleavage of MUC2 (due to impaired bicarbonate/Ca2+ chelation) prevents mucus detachment in CF.", "protein": "Meprin \u03b2", "protein_enriched": { "function": "Membrane metallopeptidase that sheds many membrane-bound proteins. Exhibits a strong preference for acidic amino acids at the P1' position. Known substrates include: FGF19, VGFA, IL1B, IL18, procollag", "gene_name": "MEP1B", "glycan_count": 8, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G11460AB", "G17601US", "G88303DD", "G19958IL", "G37135JQ", "G61846BY", "G83161QT", "G89864BN" ], "uniprot_id": "Q16820" }, "relationship_type": "causal", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Colitis (DSS-induced)", "glycan_involvement": "Indirect; mucin glycosylation may modulate protease accessibility.", "mechanism": "Meprin \u03b2 deficiency protects against DSS-induced colitis by preventing IL-18 activation; meprin \u03b1 absence aggravates colitis.", "protein": "Meprin \u03b2", "protein_enriched": { "function": "Membrane metallopeptidase that sheds many membrane-bound proteins. Exhibits a strong preference for acidic amino acids at the P1' position. Known substrates include: FGF19, VGFA, IL1B, IL18, procollag", "gene_name": "MEP1B", "glycan_count": 8, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G11460AB", "G17601US", "G88303DD", "G19958IL", "G37135JQ", "G61846BY", "G83161QT", "G89864BN" ], "uniprot_id": "Q16820" }, "relationship_type": "protective/causal", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Colitis (DSS-induced)", "glycan_involvement": "O-glycosylation and sulfation critical for barrier function.", "mechanism": "Properly glycosylated MUC2 forms a barrier protecting against colitis; altered glycosylation increases susceptibility.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC11207715" }, { "confidence": "medium", "disease": "Oral candidiasis and bacterial infections", "glycan_involvement": "O-glycosylation in VNTR region mediates microbial binding and agglutination.", "mechanism": "MUC7 exhibits antimicrobial activity against Candida albicans and Streptococcus spp.", "protein": "MUC7", "protein_enriched": { "function": "Potential calcium-dependent cell-adhesion protein", "gene_name": "PCDH9", "glycan_count": 22, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G41071NU", "G48414YA", "G00912UN", "G37995HC", "G44753VC", "G49906RN", "G58087IP", "G76295SF", "G85554PZ", "G13694XX", "G84225JN", "G62765YT", "G61256FT", "G07755XJ", "G06356OH", "G47518TP", "G82830MN", "G84452RH", "G80920RR", "G22310AV", "G38663NM", "G43089EG" ], "uniprot_id": "Q9HC56" }, "relationship_type": "protective", "source_pmcid": "PMC11207715" }, { "confidence": "low", "disease": "Infertility/subfertility", "glycan_involvement": "O-glycosylation in VNTR region modulates sperm interaction.", "mechanism": "MUC9 facilitates sperm/oocyte binding and zona pellucida penetration.", "protein": "MUC9 (OVGP1)", "relationship_type": "protective/functional", "source_pmcid": "PMC11207715" }, { "confidence": "high", "disease": "Diabetic Foot Ulcer", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Recombinant PDGF-BB promotes granulation tissue formation and wound healing.", "protein": "PDGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207742" }, { "confidence": "high", "disease": "Chronic Lower Extremity Wound", "glycan_involvement": "Glycosylation affects stability and activity.", "mechanism": "VEGF promotes angiogenesis; reduced expression impairs healing.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207742" }, { "confidence": "medium", "disease": "Diabetic Foot Ulcer", "glycan_involvement": "No direct glycan involvement specified.", "mechanism": "Reduced HIF1\u03b1 destabilizes VEGF expression, impairing angiogenesis.", "protein": "HIF1\u03b1", "relationship_type": "causal", "source_pmcid": "PMC11207742" }, { "confidence": "high", "disease": "Diabetic Foot Ulcer", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Overexpression disrupts ECM, impairs healing; inhibition improves healing.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11207742" }, { "confidence": "high", "disease": "Diabetic Foot Ulcer", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Pro-inflammatory cytokine; inhibition promotes healing.", "protein": "IL-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207742" }, { "confidence": "high", "disease": "Diabetic Foot Ulcer", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Pro-inflammatory cytokine; inhibition promotes anti-inflammatory macrophage polarization.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). 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"Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", 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"G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207770" }, { "confidence": "medium", "disease": "Brain tumors (e.g., glioma, glioblastoma)", "glycan_involvement": "Transferrin glycosylation is critical for receptor-mediated endocytosis.", "mechanism": "Transferrin-modified nanocarriers increase drug delivery to brain 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"G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207770" }, { "confidence": "medium", "disease": "Brain tumors (e.g., glioma, glioblastoma)", "glycan_involvement": "Receptor glycosylation affects ligand binding and internalization.", "mechanism": "Overexpressed on brain endothelium and tumors, mediates uptake of glycoprotein-modified nanocarriers.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207770" }, { "confidence": "medium", "disease": "Central nervous system drug delivery (general anesthesia)", "glycan_involvement": "Receptor glycosylation may modulate ligand specificity.", "mechanism": "Highly expressed in brain endothelium, mediates uptake of lactoferrin-modified liposomes.", "protein": "Lactoferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11207770" }, { "confidence": "medium", "disease": "General anesthesia (side effects reduction)", "glycan_involvement": "Glycosylation enables efficient receptor-mediated targeting.", "mechanism": "Brain-targeted delivery reduces off-target toxicity (e.g., adrenal toxicity, myoclonus) of etomidate.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron 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"G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC11207770" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Siglec-1 is a sialic-acid-binding glycoprotein; its glycosylation enables ligand recognition and cell adhesion.", "mechanism": "Siglec-1 expression on monocytes is upregulated by type I interferon signaling, reflecting IFN-driven inflammation in SLE.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "high", "disease": "Juvenile Dermatomyositis (JDM)", "glycan_involvement": "Glycosylation mediates Siglec-1's interaction with sialylated ligands on immune cells.", "mechanism": "Elevated Siglec-1 expression correlates with IFN inflammation in JDM, serving as a surrogate marker for disease activity.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "high", "disease": "Dermatomyositis (DM)", "glycan_involvement": "Sialic acid-binding via glycosylated domains is essential for Siglec-1 function.", "mechanism": "Siglec-1 upregulation on monocytes reflects IFN-driven inflammation in DM, correlating with interferon score.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "medium", "disease": "Sj\u00f6gren Syndrome (SS)", "glycan_involvement": "Glycosylation enables Siglec-1's lectin activity and immune modulation.", "mechanism": "Siglec-1 expression is increased in SS patients with IFN inflammation, even when ESR/CRP are normal.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "medium", "disease": "Undifferentiated Connective Tissue Disease (UCTD)", "glycan_involvement": "Glycosylation required for sialic acid binding and cell-cell interactions.", "mechanism": "Siglec-1 detects early IFN inflammation in UCTD, outperforming conventional markers.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "high", "disease": "Monogenic Interferonopathies", "glycan_involvement": "Glycosylation critical for Siglec-1's immune recognition functions.", "mechanism": "High Siglec-1 expression identifies IFN-driven inflammation in genetic interferonopathies (e.g., Aicardi\u2013Gouti\u00e8res syndrome, DNase2 deficiency).", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "high", "disease": "Acute Viral Infections", "glycan_involvement": "Sialic acid-binding via glycosylated domains mediates immune cell interactions.", "mechanism": "Siglec-1 is upregulated in monocytes during acute viral infections due to IFN stimulation.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "medium", "disease": "Acute Bacterial Infections", "glycan_involvement": "Glycosylation enables Siglec-1's lectin activity.", "mechanism": "Siglec-1 expression can be elevated in some bacterial infections, reflecting IFN pathway activation.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "medium", "disease": "COPA Syndrome", "glycan_involvement": "Glycosylation required for Siglec-1's immune functions.", "mechanism": "Siglec-1 detects IFN inflammation in COPA syndrome, even with normal ESR/CRP.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "low", "disease": "TRAPS", "glycan_involvement": "Glycosylation mediates Siglec-1's cell adhesion and immune recognition.", "mechanism": "Siglec-1 may be positive in TRAPS during IFN-driven flares, but not always; reflects IFN pathway involvement.", "protein": "Siglec-1 (CD169)", "relationship_type": "biomarker", "source_pmcid": "PMC11208081" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation supports ECM interactions and receptor binding.", "mechanism": "Promotes invasiveness and angiogenesis; upregulates uPA/uPAR; associated with poor prognosis.", "protein": "Thrombospondin-1 (THBS-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation modulates ECM binding and cell signaling.", "mechanism": "Upregulated in tumors; promotes proliferation, migration, EMT via AKT pathway; predicts poor prognosis.", "protein": "SPARC", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation required for secretion and ECM localization.", "mechanism": "Promotes invasion, lymphatic metastasis, EMT, and proliferation via integrin/PI3K/Akt/mTOR and Wnt/\u03b2-catenin pathways.", "protein": "Periostin", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates integrin binding.", "mechanism": "High expression linked to lymph node metastasis, tumor hypoxia, poor prognosis; activates ERK1/2, NF-\u03baB, KRAS/MEK pathways.", "protein": "Osteopontin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation affects ECM interactions and cell signaling.", "mechanism": "Elevated in advanced/recurrent HNC; promotes invasion, metastasis, EMT, and immunosuppressive microenvironment.", "protein": "Tenascin-C (TNC)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11208127" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "Glycosylation supports ECM incorporation.", "mechanism": "Inhibits EMT and MMP-7 expression; antagonizes Tiam1-driven \u03b2-catenin nuclear translocation.", "protein": "Fibulin-3", "protein_enriched": { "function": "Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulato", "gene_name": "EFEMP1", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27391WQ", "G43417UB", "G53434XO", "G57317CE", "G29068FM", "G57321FI", "G71142DF", "G49108TO" ], "uniprot_id": "Q12805" }, "relationship_type": "protective", "source_pmcid": "PMC11208127" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Glycosylation required for secretion and ECM function.", "mechanism": "Promotes proliferation, invasion, migration; downregulation inhibits autophagy and increases drug sensitivity.", "protein": "Fibulin-4", "relationship_type": "causal", "source_pmcid": "PMC11208127" }, { "confidence": "medium", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Binds \u03b2-galactoside glycans on cell surfaces.", "mechanism": "High expression correlates with poor lymphocyte infiltration and worse survival.", "protein": "Galectin-1", "relationship_type": "biomarker", "source_pmcid": "PMC11208127" }, { "confidence": "medium", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Binds \u03b2-galactoside glycans; modulates cell-cell interactions.", "mechanism": "Upregulated in pharyngeal/laryngeal SCC and HPV(+) HNC; potential therapeutic target.", "protein": "Galectin-3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Head and neck cancer (HNC)", "glycan_involvement": "Glycosylation supports ECM binding and receptor interactions.", "mechanism": "Upregulated in HNC; promotes tumor growth, stemness, and poor prognosis via integrin \u03b1v\u03b23/c-Jun/pluripotency genes.", "protein": "Connective tissue growth factor (CTGF/CCN2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11208127" }, { "confidence": "high", "disease": "Periorbital skin aging", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation is essential for its ECM function.", "mechanism": "Decreased fibronectin contributes to ECM deterioration and aging signs.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "high", "disease": "Periorbital skin aging", "glycan_involvement": "Collagen is glycosylated, affecting stability and ECM assembly.", "mechanism": "Reduced collagen I leads to loss of skin firmness and wrinkle formation.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "high", "disease": "Periorbital skin aging", "glycan_involvement": "Glycosylation modulates collagen fibril formation.", "mechanism": "Decreased collagen III impairs skin elasticity and structure.", "protein": "Collagen type III", "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "medium", "disease": "Periorbital skin aging", "glycan_involvement": "N-glycosylation critical for collagen IV network assembly.", "mechanism": "Loss of collagen IV disrupts basement membrane integrity, accelerating aging.", "protein": "Collagen type IV", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "P02462" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "high", "disease": "Loss of skin elasticity", "glycan_involvement": "Elastin is glycosylated, influencing fiber assembly and resilience.", "mechanism": "Elastin depletion reduces skin elasticity, promoting sagging and wrinkles.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "medium", "disease": "Wrinkles", "glycan_involvement": "Glycosylation required for fibronectin's ECM interactions.", "mechanism": "Reduced fibronectin impairs ECM structure, facilitating wrinkle formation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "medium", "disease": "Periorbital skin aging", "glycan_involvement": "Sialic acid is a terminal glycan on glycoproteins, modulating cell signaling.", "mechanism": "Topical sialic acid stimulates collagen synthesis and has anti-aging effects.", "protein": "N-acetylneuraminic acid (sialic acid)", "relationship_type": "protective", "source_pmcid": "PMC11208285" }, { "confidence": "medium", "disease": "Skin dehydration", "glycan_involvement": "Glycosylation affects fibronectin's hydrophilic properties.", "mechanism": "Reduced fibronectin impairs ECM water retention, leading to dehydration.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC11208285" }, { "confidence": "low", "disease": "Skin sensitivity (burning, itching, pruritus)", "glycan_involvement": "Glycosylation enhances fibronectin's barrier role.", "mechanism": "Increased fibronectin supports barrier function, reducing sensitivity.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC11208285" }, { "confidence": "low", "disease": "Skin sensitivity (burning, itching, pruritus)", "glycan_involvement": "Acts as a glycan modulator on glycoproteins involved in inflammation.", "mechanism": "Sialic acid reduces inflammation and improves barrier function.", "protein": "N-acetylneuraminic acid (sialic acid)", "relationship_type": "protective", "source_pmcid": "PMC11208285" }, { "confidence": "high", "disease": "Transplant-associated thrombotic microangiopathy (TA-TMA)", "glycan_involvement": "sC5b-9 is composed of glycosylated complement proteins; glycosylation affects stability and function.", "mechanism": "Elevated sC5b-9 indicates complement activation and predicts TA-TMA development; complement activation contributes to endothelial injury.", "protein": "sC5b-9 (soluble membrane attack complex)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11208304" }, { "confidence": "high", "disease": "Transplant-associated thrombotic microangiopathy (TA-TMA)", "glycan_involvement": "C5 glycosylation may affect its activation and interaction with inhibitors.", "mechanism": "C5 inhibition prevents formation of C5a and C5b-9, reducing endothelial damage in TA-TMA.", "protein": "Complement C5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Infection (bacterial/fungal)", "glycan_involvement": "Glycosylation of complement components influences complex formation.", "mechanism": "Elevated sC5b-9 reflects complement activation during severe infections.", "protein": "sC5b-9 (soluble membrane attack complex)", "relationship_type": "biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "high", "disease": "Infection (bacterial/fungal)", "glycan_involvement": "C3 glycosylation is critical for secretion and function.", "mechanism": "Intact C3 function is essential for opsonization and defense against pathogens post-HSCT.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "protective", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Graft-versus-host disease (GVHD)", "glycan_involvement": "C1q is a glycoprotein; glycosylation affects its immune complex binding.", "mechanism": "C1q (classical pathway) activity is retained post-HSCT; may contribute to immune complex-mediated tissue injury in GVHD.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Sinusoidal obstruction syndrome", "glycan_involvement": "CRP is glycosylated, which affects its ligand binding.", "mechanism": "CRP levels rise with endothelial injury and inflammation, as seen in sinusoidal obstruction syndrome.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Transplant-associated thrombotic microangiopathy (TA-TMA)", "glycan_involvement": "IL-6 is glycosylated, influencing secretion and receptor interaction.", "mechanism": "IL-6 is elevated in patients with complement activation and TA-TMA, reflecting systemic inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Infection (bacterial/fungal)", "glycan_involvement": "MPO glycosylation affects its stability and activity.", "mechanism": "MPO release correlates with neutrophil activation during infection.", "protein": "MPO (myeloperoxidase)", "relationship_type": "biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Infection (bacterial/fungal)", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "IL-8 is elevated during infection and complement activation.", "protein": "IL-8/CXCL8", "relationship_type": "biomarker", "source_pmcid": "PMC11208304" }, { "confidence": "medium", "disease": "Graft-versus-host disease (GVHD)", "glycan_involvement": "C3 glycosylation is essential for function.", "mechanism": "Complement activation may contribute to GVHD pathogenesis; C3 inhibition reduces cytokine release.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11208304" }, { "confidence": "high", "disease": "Organic erectile dysfunction (ED)", "glycan_involvement": "Apo A1 is a glycoprotein; glycosylation may affect its anti-atherogenic function.", "mechanism": "Lower Apo A1 levels are associated with increased risk of organic ED; Apo A1 may prevent atherosclerosis and vascular dysfunction.", "protein": "Apolipoprotein A1 (Apo A1)", "relationship_type": "causal/protective/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "medium", "disease": "Organic erectile dysfunction (ED)", "glycan_involvement": "Apo B is a glycoprotein; glycosylation may influence its role in lipid deposition.", "mechanism": "Higher Apo B levels are associated with increased risk of organic ED; Apo B promotes atherosclerosis and vascular dysfunction.", "protein": "Apolipoprotein B (Apo B)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Organic erectile dysfunction (ED)", "glycan_involvement": "Both Apo A1 and Apo B are glycoproteins; glycosylation may modulate their functional balance.", "mechanism": "Lower Apo A1/B ratio is associated with higher risk of organic ED; reflects balance between anti- and pro-atherogenic lipoproteins.", "protein": "Apolipoprotein A1/Apolipoprotein B ratio (Apo A1/B)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Organic erectile dysfunction (ED)", "glycan_involvement": "Contains Apo A1 glycoprotein; glycosylation may affect HDL function.", "mechanism": "Lower HDL levels are associated with increased risk of organic ED; HDL is anti-atherogenic, mainly via Apo A1.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "medium", "disease": "Organic erectile dysfunction (ED)", "glycan_involvement": "Contains Apo B glycoprotein; glycosylation may affect LDL atherogenicity.", "mechanism": "Higher LDL levels are associated with organic ED in univariate analysis, but not after adjusting for confounders.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Psychogenic erectile dysfunction (ED)", "glycan_involvement": "Not applicable.", "mechanism": "No significant relationship; Apo A1 not implicated in psychogenic ED.", "protein": "Apolipoprotein A1 (Apo A1)", "relationship_type": "no association", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Psychogenic erectile dysfunction (ED)", "glycan_involvement": "Not applicable.", "mechanism": "No significant relationship; Apo B not implicated in psychogenic ED.", "protein": "Apolipoprotein B (Apo B)", "relationship_type": "no association", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Psychogenic erectile dysfunction (ED)", "glycan_involvement": "Not applicable.", "mechanism": "No significant relationship; ratio not implicated in psychogenic ED.", "protein": "Apolipoprotein A1/Apolipoprotein B ratio (Apo A1/B)", "relationship_type": "no association", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may modulate Apo A1 function in CVD.", "mechanism": "Apo A1 is protective against CVD via anti-atherogenic effects.", "protein": "Apolipoprotein A1 (Apo A1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may affect Apo B's atherogenic properties.", "mechanism": "Apo B promotes atherosclerosis and is a risk factor for CVD.", "protein": "Apolipoprotein B (Apo B)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11208309" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycation (non-enzymatic addition of glucose to hemoglobin N-terminus).", "mechanism": "Reflects average blood glucose via non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "LDL particles contain glycoproteins (ApoB) with N-glycosylation affecting function.", "mechanism": "Elevated LDL-C is a risk factor for progression from prediabetes to diabetes.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "HDL contains glycoproteins (ApoA-I) with N-glycosylation modulating anti-inflammatory properties.", "mechanism": "Higher HDL-C levels protect against progression to diabetes.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC11208327" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "\u03b3-GT is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Elevated \u03b3-GT indicates liver dysfunction, which is a risk factor for diabetes.", "protein": "\u03b3-Glutamyltransferase (\u03b3-GT)", "relationship_type": "biomarker", "source_pmcid": "PMC11208327" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALT is glycosylated; glycosylation may affect secretion and activity.", "mechanism": "Elevated ALT is indicative of liver dysfunction, associated with increased diabetes risk.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11208327" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "AST is glycosylated; glycosylation may affect stability.", "mechanism": "Elevated AST is indicative of liver dysfunction, associated with increased diabetes risk.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of ApoB modulates LDL particle clearance.", "mechanism": "Elevated LDL-C increases risk for cardiovascular disease, which is comorbid with diabetes.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of ApoA-I influences anti-atherogenic functions.", "mechanism": "Higher HDL-C reduces cardiovascular risk, relevant in diabetes progression.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "Prediabetes", "glycan_involvement": "Glycation of hemoglobin reflects chronic glycemic status.", "mechanism": "HbA1c levels are used to diagnose prediabetes and monitor progression.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208327" }, { "confidence": "medium", "disease": "Fatty Liver Disease", "glycan_involvement": "Glycosylation of LDL components affects hepatic lipid metabolism.", "mechanism": "Elevated LDL-C is associated with fatty liver, which increases diabetes risk.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC11208327" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Glycosylation is essential for proper folding and function of the receptor.", "mechanism": "Targeted by inhibitors (eptifibatide) to prevent platelet aggregation and thrombosis during PCI.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208476" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Acts on glycoprotein IIb/IIIa; does not itself have glycan modifications.", "mechanism": "Inhibits glycoprotein IIb/IIIa, reducing platelet aggregation; marginally reduces cardiovascular mortality.", "protein": "Eptifibatide", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC11208476" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Inhibition reduces thrombotic complications in ACS.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208476" }, { "confidence": "high", "disease": "Acute coronary syndrome (ACS)", "glycan_involvement": "Targets glycoprotein IIb/IIIa.", "mechanism": "Used as adjunctive therapy to reduce platelet aggregation in ACS.", "protein": "Eptifibatide", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC11208476" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation affects ligand binding and receptor stability.", "mechanism": "Inhibition by eptifibatide marginally reduces cardiovascular mortality in STEMI patients.", "protein": "Glycoprotein IIb/IIIa (integrin \u03b1IIb\u03b23)", "relationship_type": "protective", "source_pmcid": "PMC11208476" }, { "confidence": "high", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 is overexpressed in LIHC tissues and correlates with poor prognosis, advanced stage, and reduced overall survival.", "protein": "KEAP1", "relationship_type": "biomarker", "source_pmcid": "PMC11208630" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "High KEAP1 expression promotes oxidative stress and abnormal immune responses, suggesting potential as a therapeutic target.", "protein": "KEAP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208630" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 overexpression enhances ROS production, cell dysfunction, and may promote tumor progression.", "protein": "KEAP1", "relationship_type": "causal", "source_pmcid": "PMC11208630" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 expression correlates with immune cell infiltration (increased Th2, decreased cytotoxic cells), indicating immune dysregulation.", "protein": "KEAP1", "relationship_type": "biomarker", "source_pmcid": "PMC11208630" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 expression correlates with liver function markers (negatively with albumin/total protein, positively with bilirubin/ALT/AST/AFP), indicating association with liver injury.", "protein": "KEAP1", "relationship_type": "biomarker", "source_pmcid": "PMC11208630" }, { "confidence": "low", "disease": "Primary biliary cirrhosis", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 is overexpressed in primary biliary cirrhosis, leading to decreased Nrf2 and downstream antioxidant molecules, promoting disease progression.", "protein": "KEAP1", "relationship_type": "causal", "source_pmcid": "PMC11208630" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 overexpression inhibits oxidative stress response, contributing to cirrhosis progression.", "protein": "KEAP1", "relationship_type": "causal", "source_pmcid": "PMC11208630" }, { "confidence": "low", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "Not directly addressed in article.", "mechanism": "KEAP1 expression is associated with drug resistance in hepatocellular carcinoma cells.", "protein": "KEAP1", "relationship_type": "biomarker", "source_pmcid": "PMC11208630" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "C1q is a highly cationic glycoprotein; glycosylation affects its structure and immune complex binding.", "mechanism": "Genetic deficiency of C1q increases risk of SLE due to impaired clearance of apoptotic bodies and immune complexes.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "Anti-C1q antibodies are IgG glycoproteins; glycosylation may affect Fc-receptor interactions and effector functions.", "mechanism": "High titers of anti-C1q antibodies are strongly associated with active LN and renal flares; levels correlate with disease activity and histological class.", "protein": "Anti-C1q antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "Glycosylation of C1q influences its immune complex binding and clearance.", "mechanism": "C1q deposition in glomeruli is a hallmark of LN; immune complexes containing C1q contribute to renal inflammation.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "IgG glycosylation may modulate antibody pathogenicity.", "mechanism": "Presence and titer of anti-C1q antibodies correlate with SLE disease activity and proteinuria.", "protein": "Anti-C1q antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "IgG glycosylation may affect epitope binding and immune activation.", "mechanism": "Anti-A08 antibodies (against C1q A-chain epitope) show higher sensitivity and specificity for active LN than conventional anti-C1q antibodies.", "protein": "Anti-A08 antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS)", "glycan_involvement": "IgG glycosylation may influence complement activation.", "mechanism": "High prevalence of anti-C1q antibodies in HUVS; these antibodies activate complement and drive vasculitis.", "protein": "Anti-C1q antibodies", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11208682" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "IgG glycosylation may affect pathogenicity.", "mechanism": "In rodents, infusion of anti-C1q antibodies leads to immune complex deposition and glomerulonephritis.", "protein": "Anti-C1q antibodies", "relationship_type": "causal", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "C3 is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Low serum C3 levels are associated with LN activity and renal flares.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC11208682" }, { "confidence": "medium", "disease": "Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS)/SLE", "glycan_involvement": "DNASE1L3 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "DNASE1L3 mutations cause monogenic lupus and are associated with HUVS and kidney involvement.", "protein": "DNASE1L3", "protein_enriched": { "function": "Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves", "gene_name": "DNASE1L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13609" }, "relationship_type": "causal", "source_pmcid": "PMC11208682" }, { "confidence": "medium", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "IgG glycosylation may modulate immune response.", "mechanism": "Anti-C3b IgG identifies LN patients in whom anti-C1q can serve as a biomarker for renal flare.", "protein": "Anti-C3b IgG", "relationship_type": "biomarker", "source_pmcid": "PMC11208682" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation required for receptor function and ligand binding.", "mechanism": "VEGFR glycoproteins regulate angiogenesis and tumor growth; siRNA targeting reduces VEGF expression and blocks angiogenesis.", "protein": "VEGFR-1/VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Cancer (various types, especially breast cancer)", "glycan_involvement": "Glycosylation modulates HB-EGF stability and receptor interaction.", "mechanism": "HB-EGF overexpression promotes tumorigenicity; siRNA targeting inhibits tumor growth.", "protein": "HB-EGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Breast cancer, gastric cancer", "glycan_involvement": "N-glycosylation affects receptor dimerization and signaling.", "mechanism": "HER-2/neu overexpression confers resistance to apoptosis; siRNA targeting reduces cancer cell survival.", "protein": "HER-2/neu", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may affect membrane localization.", "mechanism": "Bcl-2 is anti-apoptotic; siRNA targeting decreases Bcl-2 expression, promoting apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "medium", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Glycosylation influences membrane trafficking.", "mechanism": "Caveolin-2 facilitates bacterial invasion; siRNA silencing reduces pathogenesis.", "protein": "Caveolin-2", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction w", "gene_name": "CAV2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51636" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 suppresses immune response; siRNA targeting enhances anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "medium", "disease": "Pulmonary infection (MRSA)", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "Coagulase promotes MRSA virulence; siRNA silencing reduces bacterial load.", "protein": "Coagulase (Staphylocoagulase)", "protein_enriched": { "function": "Preferentially cleaves peptide bonds on the carboxyl-terminal side of aspartate and glutamate. Along with other extracellular proteases it is involved in colonization and infection of human tissues. R", "gene_name": "sspA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C1U8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "medium", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Glycosylation may affect membrane localization.", "mechanism": "MexB mediates drug resistance; siRNA targeting decreases bacterial survival.", "protein": "MexB efflux pump", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9I4S7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "Glycosylation may affect viral assembly.", "mechanism": "N protein essential for viral replication; siRNA targeting reduces infection rates.", "protein": "RSV Nucleocapsid Protein (N)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Hepatitis B virus (HBV) infection", "glycan_involvement": "N-glycosylation critical for antigenicity and secretion.", "mechanism": "HBsAg is key for viral infectivity and immune evasion; siRNA targeting reduces antigen levels and viral load.", "protein": "HBV Surface Antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208694" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "IgG glycosylation affects Fc receptor binding and anti-inflammatory activity.", "mechanism": "Intravenous immunoglobulin therapy improves neurological symptoms in ADEM by modulating immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208760" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation of IgG influences its stability and immune function in CSF.", "mechanism": "Presence of oligoclonal IgG bands in CSF indicates intrathecal IgG synthesis and supports autoimmune etiology.", "protein": "Oligoclonal bands (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC11208760" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Altered glycosylation may affect IgG aggregation and immune signaling.", "mechanism": "Oligoclonal IgG bands in CSF are a diagnostic marker for MS, reflecting chronic immune activation.", "protein": "Oligoclonal bands (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC11208760" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Fc glycan structures modulate anti-inflammatory properties.", "mechanism": "IVIG is sometimes used in MS to modulate immune response, though efficacy is variable.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208760" }, { "confidence": "medium", "disease": "Alcoholic cardiomyopathy", "glycan_involvement": "Not directly addressed; possible glycopeptide activity", "mechanism": "Reduces oxidative stress and inflammation, improves cardiac histology and function in mouse model", "protein": "Deer heart peptide", "relationship_type": "protective", "source_pmcid": "PMC11208793" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "Not specified", "mechanism": "Decreases serum CK, MDA; increases SOD, CAT; reduces proinflammatory cytokines", "protein": "Deer heart peptide", "relationship_type": "protective", "source_pmcid": "PMC11208793" }, { "confidence": "high", "disease": "Cardiac injury", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects secretion and stability", "mechanism": "Upregulated in cardiac injury; reduced by deer heart peptide", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11208793" }, { "confidence": "high", "disease": "Cardiac injury", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation modulates activity", "mechanism": "Upregulated in cardiac injury; reduced by deer heart peptide", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11208793" }, { "confidence": "high", "disease": "Cardiac injury", "glycan_involvement": "IL-1\u03b2 is a glycoprotein; glycosylation affects secretion", "mechanism": "Upregulated in cardiac injury; reduced by deer heart peptide", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11208793" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "SOD is glycosylated; glycosylation affects stability", "mechanism": "Decreased in cardiac injury; increased by deer heart peptide, indicating reduced oxidative stress", "protein": "SOD", "relationship_type": "biomarker", "source_pmcid": "PMC11208793" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "CAT is glycosylated; glycosylation affects activity", "mechanism": "Decreased in cardiac injury; increased by deer heart peptide, indicating improved antioxidant defense", "protein": "CAT", "relationship_type": "biomarker", "source_pmcid": "PMC11208793" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "CK is glycosylated; glycosylation may affect serum stability", "mechanism": "Increased in cardiac injury; decreased by deer heart peptide, indicating reduced myocardial damage", "protein": "CK", "relationship_type": "biomarker", "source_pmcid": "PMC11208793" }, { "confidence": "low", "disease": "Myocardial ischemia", "glycan_involvement": "Not specified", "mechanism": "Proposed to improve blood flow and reduce ischemic damage (based on cited literature)", "protein": "Deer heart peptide", "relationship_type": "protective (suggested)", "source_pmcid": "PMC11208793" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "Not specified", "mechanism": "Proposed to improve cardiac function and reduce fibrosis (based on cited literature)", "protein": "Deer heart peptide", "relationship_type": "protective (suggested)", "source_pmcid": "PMC11208793" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Spike protein is highly glycosylated; glycan structures may influence immune recognition and mimicry.", "mechanism": "Molecular mimicry between spike protein and host antigens may trigger autoimmune neuropathy.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11208806" }, { "confidence": "medium", "disease": "Guillain\u2013Barr\u00e9 Syndrome", "glycan_involvement": "Glycosylation of spike protein may affect antigenicity and immune cross-reactivity.", "mechanism": "Molecular mimicry and immune activation post-vaccination may induce autoimmunity.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11208806" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG therapy modulates immune response and improves CIDP symptoms.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208806" }, { "confidence": "low", "disease": "Acute Disseminated Encephalomyelitis", "glycan_involvement": "Glycosylation may affect immune activation.", "mechanism": "Immune response to spike protein may trigger CNS autoimmunity.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11208806" }, { "confidence": "low", "disease": "Myelitis", "glycan_involvement": "Glycan structures may contribute to antigenicity.", "mechanism": "Autoimmune reaction post-vaccination possibly due to molecular mimicry.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11208806" }, { "confidence": "low", "disease": "Encephalitis", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Immune activation following vaccination may induce CNS inflammation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC11208806" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry via binding to ACE2 receptor; major antigen for neutralizing antibodies and vaccines.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Facilitates viral entry into host cells via ACE2; target for vaccine development.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation modulates antigenicity and host interaction.", "mechanism": "Enables viral entry via host receptor binding; immunogenic target.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts vaccine antigenicity and antibody response.", "mechanism": "Targeted by mRNA, DNA, subunit, and vector vaccines to induce neutralizing antibodies.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11208815" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 influences S protein binding affinity.", "mechanism": "Host receptor for S protein; mediates viral entry into respiratory and other tissues.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Acts as host restriction factor, limiting coronavirus replication.", "protein": "TRIM56", "protein_enriched": { "function": "E3 ubiquitin ligase that plays a crucial role in the activation of the IKBKE-dependent branch of the type I interferon signaling pathway (PubMed:24882218, PubMed:31694946). In concert with the ubiquit", "gene_name": "TRIM6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9C030" }, "relationship_type": "protective", "source_pmcid": "PMC11208815" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Induces antibody response; used in diagnostics, but antibodies are non-neutralizing.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208815" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation stabilizes viral envelope.", "mechanism": "Structural protein; induces IgG response in animal models.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208815" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "PF4 is glycosylated; glycan status may affect immunogenicity.", "mechanism": "Adenovirus vector vaccines can induce anti-PF4 antibodies, leading to thrombosis.", "protein": "Platelet factor 4 (PF4)", "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates immune activation.", "mechanism": "S protein-mediated infection triggers cytokine storm, leading to ARDS.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11208815" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects stability and secretion during inflammation.", "mechanism": "Serum levels rise in response to inflammatory cytokines and bacterial infection; correlates with severity and mortality.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation required for pentameric structure and function.", "mechanism": "Acute phase reactant; levels increase rapidly during infection and inflammation, predicting severity and mortality.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates receptor binding and stability.", "mechanism": "Pro-inflammatory cytokine; elevated levels independently predict 28-day mortality.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation influences secretion and immunomodulatory activity.", "mechanism": "Anti-inflammatory cytokine; increased levels correlate with higher mortality risk.", "protein": "Interleukin-10", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect peptide processing and stability.", "mechanism": "Precursor of adrenomedullin; serum levels proportional to infection severity and predictive of mortality.", "protein": "Proadrenomedullin", "protein_enriched": { "function": "Serine protease which possesses both gelatinolytic and caseinolytic activities. Shows a preference for Arg in the P1 position", "gene_name": "TMPRSS11E", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9UL52" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation status may affect half-life and function.", "mechanism": "Negative acute phase reactant; hypoalbuminemia predicts poor prognosis and mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation influences degradation and clearance.", "mechanism": "Elevated in sepsis; indicates increased risk of VTE and inflammation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Cardiac dysfunction (septic cardiomyopathy)", "glycan_involvement": "Glycosylation affects cardiac release and detection.", "mechanism": "Elevated levels predict cardiac injury and mortality in sepsis.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Cardiac dysfunction (septic cardiomyopathy)", "glycan_involvement": "Glycosylation modulates peptide stability and bioactivity.", "mechanism": "Elevated levels better predict ICU/90-day mortality than troponin T.", "protein": "N-terminal pro-B-type natriuretic peptide", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Surface glycoproteins mediate cell-cell interactions and immune regulation.", "mechanism": "Increased Treg cells exacerbate immunosuppression and correlate with severity and mortality.", "protein": "CD4+CD25+ Regulatory T Cell surface proteins", "relationship_type": "biomarker", "source_pmcid": "PMC11208822" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "N-glycosylation collaborates with Wnt signaling to induce CTHRC1 and drive HNSCC cell migration.", "mechanism": "High CTHRC1 expression correlates with advanced stage, poor prognosis, and increased immune infiltration (especially M2 macrophages) in HNSCC.", "protein": "CTHRC1", "protein_enriched": { "function": "", "gene_name": "UPRT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BW1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "N-glycosylation modulates CTHRC1 function and cell migration.", "mechanism": "CTHRC1 influences immune cell composition, especially promoting M2 macrophage polarization, contributing to immune evasion and tumor progression.", "protein": "CTHRC1", "protein_enriched": { "function": "", "gene_name": "UPRT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BW1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not specified in this article.", "mechanism": "Promotes cell proliferation and metastasis, indicating poor prognosis.", "protein": "CTHRC1", "protein_enriched": { "function": "", "gene_name": "UPRT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BW1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Not specified in this article.", "mechanism": "Associated with immunotherapy and angiogenesis; high expression correlates with poor prognosis.", "protein": "CTHRC1", "protein_enriched": { "function": "", "gene_name": "UPRT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96BW1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "CD276 is a glycoprotein; glycosylation may affect immune modulation.", "mechanism": "Elevated CD276 expression suppresses anti-tumor T-cell responses and correlates with poor prognosis; positively correlated with CTHRC1.", "protein": "CD276", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "TNFSF4 is a glycoprotein; glycosylation may affect ligand-receptor interactions.", "mechanism": "Promotes T cell activation and proliferation; high expression correlates with CTHRC1 and may facilitate chemoresistance.", "protein": "TNFSF4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "POSTN is a glycoprotein; glycosylation affects ECM interactions.", "mechanism": "Co-expressed with CTHRC1; involved in ECM organization and tumor progression.", "protein": "POSTN", "relationship_type": "biomarker", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "SPARC is a glycoprotein; glycosylation modulates ECM binding.", "mechanism": "Co-expressed with CTHRC1; involved in ECM remodeling and tumor progression.", "protein": "SPARC", "relationship_type": "biomarker", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "Collagens are glycoproteins; glycosylation affects fibril formation.", "mechanism": "Co-expressed with CTHRC1; involved in collagen fibril organization and ECM structure in tumors.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC11209980" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "TIM3 is a glycoprotein; glycosylation modulates immune checkpoint function.", "mechanism": "Positively correlated with CTHRC1; involved in immune checkpoint regulation.", "protein": "HAVCR2 (TIM3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11209980" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Not directly discussed; AKR1B10 may be glycosylated but not specified.", "mechanism": "Upregulated in NASH; promotes fatty acid and triglyceride synthesis by stabilizing ACC\u03b1.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11210137" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "No direct evidence of glycosylation involvement in article.", "mechanism": "Upregulated in NASH; catalyzes Acetyl-CoA to Malonyl-CoA, driving FFA and TG synthesis.", "protein": "ACC\u03b1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11210137" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Not specified.", "mechanism": "Abnormal upregulation during progression from NAFLD to NASH; facilitates lipid accumulation.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11210137" }, { "confidence": "medium", "disease": "NAFLD/NASH", "glycan_involvement": "Transmembrane glycoprotein; glycosylation may affect function but not detailed.", "mechanism": "Altered expression is a focal point for monitoring lipid synthesis in NAFLD/NASH.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210137" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Highly expressed in cancer tissues; may promote lipid synthesis and tumorigenesis.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11210137" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Upregulation associated with progression to fibrosis in NASH.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11210137" }, { "confidence": "low", "disease": "NASH", "glycan_involvement": "Not specified.", "mechanism": "Elevated in NASH; involved in disease progression.", "protein": "TAZ (WWTR1)", "relationship_type": "biomarker", "source_pmcid": "PMC11210137" }, { "confidence": "low", "disease": "NASH", "glycan_involvement": "Not specified.", "mechanism": "Elevated in NASH; may regulate vascular and inflammatory responses.", "protein": "RUNX1", "protein_enriched": { "function": "Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3',", "gene_name": "RUNX1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q01196" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210137" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Not specified.", "mechanism": "Expression correlates with metabolic syndrome traits, including obesity.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210137" }, { "confidence": "low", "disease": "Type 2 Diabetes", "glycan_involvement": "Not specified.", "mechanism": "Expression correlates with metabolic syndrome traits, including diabetes.", "protein": "AKR1B10", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9", "gene_name": "AKR1B10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60218" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210137" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "MPO is a glycoprotein; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Autoantibodies against MPO (p-ANCA) drive neutrophil activation and vascular damage.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11210192" }, { "confidence": "high", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation may influence immune recognition; PTU-induced conformational changes may expose glycan epitopes.", "mechanism": "PTU modifies MPO structure, breaking tolerance and inducing anti-MPO autoantibodies.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "PR3 glycosylation may modulate antigenicity and immune response.", "mechanism": "Anti-PR3 autoantibodies (c-ANCA) activate neutrophils, leading to vasculitis.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation affects beta-2 glycoprotein I structure and immunogenicity.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are observed in PTU-induced AAV.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Lactoferrin glycosylation may influence autoantibody binding.", "mechanism": "Autoantibodies against lactoferrin are found in PTU-induced AAV.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation may affect antigen presentation.", "mechanism": "Autoantibodies against cathepsin G are present in PTU-induced AAV.", "protein": "Cathepsin G", "protein_enriched": { "function": "Serine protease with trypsin- and chymotrypsin-like specificity (PubMed:29652924, PubMed:8194606). Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of ", "gene_name": "CTSG", "glycan_count": 7, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G05049YU", "G31852PQ", "G41247ZX", "G47644PP", "G88891KO", "G49108TO" ], "uniprot_id": "P08311" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies against neutrophil elastase are detected in PTU-induced AAV.", "protein": "Neutrophil elastase", "protein_enriched": { "function": "Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of", "gene_name": "ELANE", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G93279DZ", "G00395TQ", "G08290VR", "G11870QZ", "G27058EU", "G28681TP", "G29299MO", "G47644PP", "G47950XN", "G61334IA", "G82348BZ", "G00912UN", "G11314AS", "G25637MV", "G36379GD", "G59626AS", "G72291OX", "G95865ZB" ], "uniprot_id": "P08246" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Autoantibodies against azurocidin are found in PTU-induced AAV.", "protein": "Azurocidin", "protein_enriched": { "function": "This is a neutrophil granule-derived antibacterial and monocyte- and fibroblast-specific chemotactic glycoprotein. Binds heparin. The cytotoxic action is limited to many species of Gram-negative bacte", "gene_name": "AZU1", "glycan_count": 28, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G07755XJ", "G11101UV", "G45504EY", "G50856PC", "G51653BI", "G56770VP", "G60834IK", "G77547TA", "G83646BJ", "G86880BF", "G92135MA", "G04657PL", "G08290VR", "G11314AS", "G11870QZ", "G12313PD", "G14669DU", "G22572EH", "G27058EU", "G28681TP", "G29299MO", "G36379GD", "G47644PP", "G47950XN", "G84862VB", "G85269DF", "G92275SC", "G95865ZB" ], "uniprot_id": "P20160" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation of MPO may affect NET formation and immune interactions.", "mechanism": "MPO-rich NETs promote endothelial damage and hypercoagulability, increasing VTE risk in AAV.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "causal", "source_pmcid": "PMC11210192" }, { "confidence": "medium", "disease": "Drug-induced AAV (PTU-induced)", "glycan_involvement": "Glycosylation may affect molecular mimicry and immune cross-reactivity.", "mechanism": "Structural similarity to MPO may contribute to loss of tolerance and autoimmunity in PTU-induced AAV.", "protein": "Thyroid peroxidase", "relationship_type": "causal", "source_pmcid": "PMC11210192" }, { "confidence": "high", "disease": "Posthepatectomy liver failure (PHLF)", "glycan_involvement": "sST2 is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "sST2 levels rise rapidly after liver resection and predict PHLF \u2265 grade B as early as postoperative day 1.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may modulate sST2's immune interactions.", "mechanism": "sST2 plasma and tissue levels are elevated in HCC patients post-resection.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Hepatic alveolar echinococcosis (HAE)", "glycan_involvement": "Glycosylation may influence sST2's release and function.", "mechanism": "sST2 levels are higher in HAE patients after hepatectomy, reflecting immune/inflammatory response.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Hepatitis B virus (HBV) infection", "glycan_involvement": "Glycosylation may affect sST2's immunomodulatory properties.", "mechanism": "HBV-infected patients show higher sST2 levels post-resection.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation impacts sST2's stability in circulation.", "mechanism": "sST2 is established as a prognostic marker in heart failure.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Posthepatectomy liver failure (PHLF)", "glycan_involvement": "IL-33 is glycosylated; glycosylation may affect its release from damaged cells.", "mechanism": "IL-33 levels increase after hepatectomy but have poor predictive value for PHLF.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may regulate IL-33's activity and stability.", "mechanism": "IL-33 tissue and plasma levels are elevated in HCC, but not as predictive as sST2.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "high", "disease": "Postoperative morbidity (Clavien-Dindo IIIa or higher)", "glycan_involvement": "Glycosylation may affect sST2's interaction with immune cells.", "mechanism": "High sST2 levels on POD1 are associated with increased severe postoperative complications.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Liver regeneration after injury", "glycan_involvement": "Glycosylation could influence sST2's regulatory functions.", "mechanism": "sST2 may modulate the balance between inflammation and regeneration post-hepatectomy.", "protein": "Soluble suppression of tumourigenicity 2 (sST2)", "relationship_type": "biomarker/possible regulator", "source_pmcid": "PMC11210312" }, { "confidence": "medium", "disease": "Liver injury (acetaminophen-induced)", "glycan_involvement": "Glycosylation may affect IL-33's release and activity.", "mechanism": "IL-33 deficiency increases hepatocyte autophagy and tissue injury in AILI models.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "protective", "source_pmcid": "PMC11210312" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not directly discussed in this article; TTN is a known glycoprotein, but glycosylation's role in this mechanism is not specified.", "mechanism": "Splice site mutations (especially truncating variants in the A-band region) lead to production of truncated titin protein, disrupting sarcomere structure and muscle contraction, resulting in DCM.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "Presence of TTN truncating or splice variants is a genetic marker for familial DCM and can guide genetic counseling and risk assessment.", "protein": "Titin (TTN)", "relationship_type": "biomarker", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "Identification of TTN splicing mutations may inform targeted therapies or interventions for DCM patients.", "protein": "Titin (TTN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210389" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "Mutations in the fibronectin type III domain of the A-band are most frequently associated with severe DCM.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "Variants closer to the C-terminus (A-band) result in more severe DCM phenotypes.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "TTN truncating variants are associated with early muscle weakness, reduced reflexes, and respiratory issues in DCM.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "TTN truncating variants are more common in advanced DCM requiring assist devices or transplantation.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "TTN truncating variants lead to lower stroke volume, thinner left ventricle walls, and more severe left ventricular dysfunction.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "TTN truncating variants are associated with sustained ventricular tachycardia but good response to medical treatment.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Not specified in this article.", "mechanism": "TTN variants in the I-band are more tolerated due to alternative splicing, resulting in less severe DCM.", "protein": "Titin (TTN)", "relationship_type": "causal", "source_pmcid": "PMC11210389" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation modulates ICAM-1 function and leukocyte binding.", "mechanism": "Increased ICAM-1 expression on venules promotes leukocyte extravasation, contributing to joint inflammation and damage.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Venous thrombosis", "glycan_involvement": "Glycosylation affects PECAM-1 adhesive properties.", "mechanism": "PECAM-1 mediates leukocyte transmigration and endothelial integrity; dysfunction can promote thrombosis.", "protein": "PECAM-1", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for eff", "gene_name": "Pecam1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G25079LO", "G24748EV", "G15664MX", "G72747WU", "G31986NC", "G80920RR", "G49108TO" ], "uniprot_id": "Q08481" }, "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation regulates VE-cadherin stability and cell-cell adhesion.", "mechanism": "Altered VE-cadherin disrupts endothelial junctions, facilitating tumor cell intravasation.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates tight junction assembly.", "mechanism": "Reduced claudin-5 impairs blood-brain barrier, increasing neuroinflammation.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects occludin localization and function.", "mechanism": "Loss of occludin weakens BBB, contributing to disease progression.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation regulates receptor-mediated clearance functions.", "mechanism": "LSEC dysfunction (including altered stabilin-2) is implicated in liver disease progression.", "protein": "Stabilin-2", "relationship_type": "biomarker", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "N-glycosylation is essential for thrombomodulin anticoagulant activity.", "mechanism": "Endothelial thrombomodulin loss increases coagulopathy and inflammation.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210405" }, { "confidence": "high", "disease": "Cancer metastasis", "glycan_involvement": "N-glycosylation required for VEGFR cell surface expression and ligand binding.", "mechanism": "VEGFR signaling drives pathological angiogenesis in tumors.", "protein": "VEGFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Venous thrombosis", "glycan_involvement": "Glycosylation modulates vWF multimerization and function.", "mechanism": "Elevated vWF indicates endothelial activation and risk of thrombosis.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11210405" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation influences ICAM-1-mediated leukocyte adhesion.", "mechanism": "ICAM-1 upregulation on venular endothelium facilitates immune cell infiltration into CNS.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11210405" }, { "confidence": "high", "disease": "Neonatal hyperbilirubinemia", "glycan_involvement": "HDL glycosylation may affect its anti-inflammatory and lipid transport functions.", "mechanism": "Lower maternal HDL levels are associated with increased risk of neonatal hyperbilirubinemia in ICP pregnancies.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Neonatal cardiac injury", "glycan_involvement": "HDL glycosylation may modulate its protective cardiovascular effects.", "mechanism": "Lower maternal HDL levels are associated with increased risk of neonatal cardiac injury in ICP pregnancies.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Neonatal hyperbilirubinemia", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Higher maternal ALT/AST ratio predicts increased risk of neonatal hyperbilirubinemia in ICP.", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Neonatal cardiac injury", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Higher maternal ALT/AST ratio predicts increased risk of neonatal cardiac injury in ICP.", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11210484" }, { "confidence": "medium", "disease": "Preterm birth", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Higher maternal ALT/AST ratio is associated with increased risk of preterm birth in ICP.", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11210484" }, { "confidence": "medium", "disease": "Neonatal respiratory distress", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Higher maternal ALT/AST ratio is associated with increased risk of neonatal respiratory distress in ICP.", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "HDL glycosylation may influence its anti-inflammatory and lipid transport functions.", "mechanism": "Lower HDL levels are associated with ICP severity and adverse outcomes.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Higher ALT/AST ratio correlates with ICP severity and adverse outcomes.", "protein": "ALT/AST ratio", "relationship_type": "biomarker", "source_pmcid": "PMC11210484" }, { "confidence": "medium", "disease": "Preterm birth", "glycan_involvement": "HDL glycosylation may affect anti-inflammatory properties.", "mechanism": "Lower maternal HDL may increase risk of preterm birth in ICP.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11210484" }, { "confidence": "medium", "disease": "Neonatal respiratory distress", "glycan_involvement": "HDL glycosylation may affect anti-inflammatory properties.", "mechanism": "Lower maternal HDL may increase risk of neonatal respiratory distress in ICP.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11210484" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation stabilizes SOD structure and activity.", "mechanism": "Decreased SOD activity indicates increased oxidative stress in CP-induced toxicity.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation affects CAT secretion and stability.", "mechanism": "Reduced CAT activity reflects oxidative damage in liver and serum after CP treatment.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation is essential for platelet glycoprotein function and clearance.", "mechanism": "CP-induced bone marrow suppression reduces platelet glycoprotein expression, leading to thrombocytopenia.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "LDL glycosylation modulates receptor binding and clearance.", "mechanism": "CP increases LDL levels, indicating metabolic disturbance.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "HDL glycosylation affects anti-atherogenic properties.", "mechanism": "CP decreases HDL, contributing to dyslipidemia.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Liver toxicity", "glycan_involvement": "Glycosylation may influence AST serum stability.", "mechanism": "Elevated AST reflects hepatocellular injury after CP exposure.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Liver toxicity", "glycan_involvement": "Glycosylation may affect ALT secretion.", "mechanism": "Increased ALT is a marker of CP-induced liver damage.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "medium", "disease": "Liver toxicity", "glycan_involvement": "ALP glycosylation modulates enzyme activity and clearance.", "mechanism": "ALP elevation indicates cholestatic or hepatocellular injury from CP.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210696" }, { "confidence": "low", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation affects enzyme localization and function.", "mechanism": "M. sativa inhibits thromboxane synthesis, reducing platelet aggregation.", "protein": "Thromboxane synthase (platelet glycoprotein-related)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210696" }, { "confidence": "low", "disease": "Myelosuppression", "glycan_involvement": "Glycosylation is critical for CSF receptor function.", "mechanism": "M. sativa may stimulate CSF receptor signaling, aiding hematopoietic recovery.", "protein": "Colony stimulating factor receptor (CSF receptor)", "relationship_type": "protective", "source_pmcid": "PMC11210696" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation affects TSH stability and secretion.", "mechanism": "TSH levels decrease in diabetic rats, indicating thyroid axis dysfunction.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation modulates ALP activity and serum half-life.", "mechanism": "ALP levels increase in diabetic rats, indicating hepatic injury.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Minor glycosylation may affect stability.", "mechanism": "AST levels increase in diabetes, reflecting liver damage.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Minor glycosylation may affect stability.", "mechanism": "ALT levels increase in diabetes, indicating hepatocellular injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "TSH glycosylation affects receptor binding and immune recognition.", "mechanism": "Autoimmune attack (TPO Ab) reduces TSH transcription and T3/T4 expression.", "protein": "TSH", "relationship_type": "causal", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "N-glycosylation required for proper receptor function.", "mechanism": "GLP-1R agonists modulate TSH levels and improve metabolic profile.", "protein": "GLP-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation modulates CRP activity and clearance.", "mechanism": "CRP levels increase in diabetes, reflecting systemic inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "IL-6 elevation in diabetes contributes to immune dysfunction and thyroid hormone disruption.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Diabetic ketoacidosis", "glycan_involvement": "N-glycosylation affects TSH serum levels.", "mechanism": "TSH decreases in diabetic ketoacidosis, indicating severe thyroid axis suppression.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Antibody glycosylation modulates immune effector function.", "mechanism": "Autoantibody attacks thyroid tissue, reducing TSH and T3/T4.", "protein": "TPO Ab", "relationship_type": "causal", "source_pmcid": "PMC11210701" }, { "confidence": "medium", "disease": "respiratory distress", "glycan_involvement": "Fibrinogen is N-glycosylated, which can modulate its function and clearance during inflammation.", "mechanism": "Elevated fibrinogen observed during acute respiratory distress, reflecting inflammatory or stress response.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "medium", "disease": "respiratory distress", "glycan_involvement": "CRP is glycosylated, affecting its stability and immune recognition.", "mechanism": "CRP is measured to assess inflammation; normal CRP suggests non-infectious etiology.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "low", "disease": "metabolic acidosis", "glycan_involvement": "Glycosylation can influence fibrinogen's role in coagulation during acidosis.", "mechanism": "Fibrinogen elevation may accompany metabolic acidosis as part of acute phase response.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "medium", "disease": "respiratory distress", "glycan_involvement": "Heparin cofactor II is glycosylated, which is essential for its anticoagulant activity.", "mechanism": "Heparin infusion used for management; heparin acts via glycoprotein cofactors.", "protein": "heparin cofactor II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11227674" }, { "confidence": "medium", "disease": "septic shock", "glycan_involvement": "Altered glycosylation in sepsis can affect fibrinogen function.", "mechanism": "Fibrinogen levels are monitored in septic shock for coagulopathy.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "medium", "disease": "septic shock", "glycan_involvement": "CRP glycosylation modulates its immune activity.", "mechanism": "CRP is elevated in septic shock; normal CRP helps rule out infection.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "low", "disease": "acute respiratory distress syndrome (ARDS)", "glycan_involvement": "N-glycosylation affects fibrinogen's role in fibrin formation in ARDS.", "mechanism": "Fibrinogen may be elevated in ARDS due to inflammation and coagulation activation.", "protein": "fibrinogen", "relationship_type": "biomarker", "source_pmcid": "PMC11227674" }, { "confidence": "medium", "disease": "Hematohidrosis", "glycan_involvement": "Glycosylation affects \u03b22-adrenoceptor localization and function on endothelial cells.", "mechanism": "\u03b22-adrenoceptors on endothelial cells mediate vasodilation via NO release; excessive activation leads to vessel rupture and blood entering sweat glands.", "protein": "Capillary endothelial cell \u03b22-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC11227682" }, { "confidence": "low", "disease": "Vasculitis", "glycan_involvement": "Endothelial glycoprotein glycosylation modulates vascular integrity.", "mechanism": "Pathological vasculitis may involve altered endothelial glycoprotein function, contributing to capillary fragility.", "protein": "Capillary endothelial cell \u03b22-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC11227682" }, { "confidence": "high", "disease": "Recent Streptococcal Infection", "glycan_involvement": "Immunoglobulin glycosylation affects antibody stability and function.", "mechanism": "Elevated antistreptolysin O antibody titers indicate recent streptococcal infection.", "protein": "Antistreptolysin O antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11227682" }, { "confidence": "medium", "disease": "Hematohidrosis", "glycan_involvement": "Fibrinogen glycosylation is essential for clotting function.", "mechanism": "Normal fibrinogen levels help exclude coagulopathies in hematohidrosis diagnosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11227682" }, { "confidence": "low", "disease": "Vasculitis", "glycan_involvement": "Glycosylation modulates fibrinogen's inflammatory properties.", "mechanism": "Fibrinogen levels may be altered in vasculitis due to inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11227682" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "OX40L is a glycoprotein; glycosylation may affect ligand-receptor interaction and immune signaling.", "mechanism": "OX40/OX40L signaling promotes T cell survival, effector phenotype, and adipose tissue inflammation, contributing to insulin resistance.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "causal", "source_pmcid": "PMC11232195" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Polymorphisms may alter OX40L expression or glycosylation, affecting immune activation.", "mechanism": "Promoter polymorphisms (rs3850641 G allele, rs1234313 and rs10912580 A/G genotypes) are associated with decreased risk of T2DM in Iranians.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "protective", "source_pmcid": "PMC11232195" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Soluble OX40L is glycosylated; glycosylation may influence stability and detection.", "mechanism": "Serum soluble OX40L levels are elevated in T1DM patients, correlating with disease activity.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11232195" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation may modulate OX40L function in immune synapse.", "mechanism": "OX40/OX40L pathway is implicated in T cell-mediated autoimmune inflammation.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "causal", "source_pmcid": "PMC11232195" }, { "confidence": "medium", "disease": "Graves\u2019 Hyperthyroidism", "glycan_involvement": "Glycosylation may affect OX40L stability and immune cell interaction.", "mechanism": "OX40/OX40L signaling involved in autoimmune thyroid inflammation.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "causal", "source_pmcid": "PMC11232195" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation may influence OX40L-mediated T cell activation.", "mechanism": "OX40L gene polymorphisms associated with SLE susceptibility.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "causal", "source_pmcid": "PMC11232195" }, { "confidence": "low", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation may affect OX40L expression in tumor microenvironment.", "mechanism": "OX40L gene polymorphisms studied in bladder cancer risk.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11232195" }, { "confidence": "low", "disease": "Cerebral Arterial Thrombosis", "glycan_involvement": "Glycosylation may impact OX40L-mediated vascular inflammation.", "mechanism": "OX40L gene polymorphisms associated with risk of thrombosis.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11232195" }, { "confidence": "low", "disease": "Atherosclerotic Disorders", "glycan_involvement": "Glycosylation may modulate OX40L function in vascular immune responses.", "mechanism": "OX40L gene polymorphisms linked to atherosclerosis susceptibility.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11232195" }, { "confidence": "low", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may affect OX40L expression in tumor cells.", "mechanism": "OX40L gene polymorphisms (rs3850641 G allele, rs10912580 A allele) associated with breast cancer risk in Chinese Han population.", "protein": "OX40L (CD252, TNFSF4, GP34)", "protein_enriched": { "function": "Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N", "gene_name": "TNFRSF11A", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9Y6Q6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11232195" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation stabilizes PON1 structure and function on HDL particles.", "mechanism": "HDL-associated PON1 has antioxidant and anti-atherosclerotic properties, protecting against lipid oxidation and endothelial dysfunction.", "protein": "Paraoxonase-1 (PON1)", "relationship_type": "protective", "source_pmcid": "PMC11235809" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "CRP is heavily glycosylated, which affects its solubility and immune interactions.", "mechanism": "CRP levels increase as a marker of acute phase inflammation after tissue injury.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Muscle damage", "glycan_involvement": "Minor glycosylation may affect clearance rate.", "mechanism": "Elevated myoglobin indicates skeletal muscle damage post-race.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "Glycosylation may modulate stability and detection.", "mechanism": "Increased troponin-I reflects myocardial overstimulation and cardiac muscle injury.", "protein": "Troponin-I", "protein_enriched": { "function": "Involved in the binding of tRNA to the ribosomes", "gene_name": "rps10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19460" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "Glycosylation affects NT-proBNP half-life and immunoreactivity.", "mechanism": "Elevated NT-proBNP is a marker of cardiac stress and injury.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Muscle damage", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Higher LDH reflects muscle cell turnover and damage; positively correlated with endurance performance.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation influences ALT secretion and activity.", "mechanism": "Elevated ALT indicates hepatocellular injury, negatively correlated with performance.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation is essential for GGT membrane localization.", "mechanism": "Higher GGT levels suggest liver stress or injury, negatively correlated with performance.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11235809" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation modulates anti-inflammatory properties.", "mechanism": "Higher HDL/LDL ratio is associated with better performance and cardiovascular protection.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11235809" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycoprotein glycosylation affects receptor binding and clearance.", "mechanism": "LDL oxidation contributes to plaque formation and vascular disease.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11235809" }, { "confidence": "high", "disease": "cancer", "glycan_involvement": "Shifts O-glycosylation pathway, increasing sialyl Tn antigen expression.", "mechanism": "Overexpression leads to altered glycosylation, producing truncated O-glycans associated with tumor progression.", "protein": "ST6GalNAc1", "relationship_type": "causal", "source_pmcid": "PMC11236981" }, { "confidence": "high", "disease": "cancer", "glycan_involvement": "Incomplete O-glycan synthesis leads to STn display on cell surface.", "mechanism": "STn expression correlates with poor prognosis and metastasis.", "protein": "sialyl Tn antigen (STn)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "high", "disease": "cancer", "glycan_involvement": "Result from altered glycosylation in tumor cells.", "mechanism": "Presence of truncated O-glycans is linked to poor cancer diagnosis and prognosis.", "protein": "truncated O-glycans", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "medium", "disease": "cancer", "glycan_involvement": "EVs carry parent cell glycan signatures.", "mechanism": "Altered glycoprotein/glycolipid patterns in extracellular vesicles reflect tumor subtype.", "protein": "glycoconjugates (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "medium", "disease": "cancer", "glycan_involvement": "Surface glycan patterns on EVs reflect those of originating cancer cells.", "mechanism": "EV glycoprotein content mirrors tumor cell glycosylation, enabling subtype discrimination.", "protein": "extracellular vesicle glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "low", "disease": "autoimmune diseases", "glycan_involvement": "Disease-specific glycan changes in EVs.", "mechanism": "Altered glycoprotein/lipoprotein patterns in EVs are considered for early diagnosis.", "protein": "glycoconjugates (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "low", "disease": "cardiovascular diseases", "glycan_involvement": "Reflects pathophysiological changes in glycosylation.", "mechanism": "EV glycoprotein/lipoprotein content may indicate disease state.", "protein": "glycoconjugates (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "low", "disease": "infectious diseases", "glycan_involvement": "Altered glycosylation in response to infection.", "mechanism": "EV glycoprotein/lipoprotein patterns can serve as early biomarkers.", "protein": "glycoconjugates (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "low", "disease": "metabolic diseases", "glycan_involvement": "Disease-specific glycan changes in EVs.", "mechanism": "EV glycoprotein/lipoprotein content may reflect metabolic disease state.", "protein": "glycoconjugates (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11236981" }, { "confidence": "medium", "disease": "cardiovascular diseases", "glycan_involvement": "EVs carry functional glycoproteins from parental cells.", "mechanism": "Exosome glycoproteins mimic cardioprotective and reparative responses.", "protein": "progenitor cell-derived exosome glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11236981" }, { "confidence": "high", "disease": "Hemochromatosis", "glycan_involvement": "HFE is a glycoprotein; glycosylation is required for proper folding and cell surface expression.", "mechanism": "HFE mutations (especially p.C282Y) disrupt hepcidin regulation, increasing iron absorption and causing iron overload.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11242024" }, { "confidence": "high", "disease": "Hemochromatosis", "glycan_involvement": "Transferrin is N-glycosylated, affecting its stability and serum half-life.", "mechanism": "Transferrin saturation is elevated in HC and used as an early diagnostic marker.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242024" }, { "confidence": "high", "disease": "Hemochromatosis", "glycan_involvement": "Hepcidin is a glycopeptide; glycosylation may affect secretion and stability.", "mechanism": "HFE mutations lead to hepcidin deficiency, resulting in unregulated iron absorption.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "Ferroportin is glycosylated; glycosylation may affect cell surface localization.", "mechanism": "Mutations cause hepcidin resistance, leading to iron overload (non-HFE HC).", "protein": "Ferroportin (SLC40A1)", "relationship_type": "causal", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "TFR2 is a glycoprotein; glycosylation is important for function.", "mechanism": "TFR2 mutations impair hepcidin regulation, causing iron overload (non-HFE HC).", "protein": "Transferrin receptor 2 (TFR2)", "protein_enriched": { "function": "Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation", "gene_name": "TFR2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9UP52" }, "relationship_type": "causal", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "Ceruloplasmin is heavily glycosylated, affecting stability and secretion.", "mechanism": "Ceruloplasmin gene mutations (aceruloplasminemia) can mimic iron overload syndromes.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "differential diagnosis", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Alpha-fetoprotein is glycosylated; glycoforms may affect diagnostic specificity.", "mechanism": "Used in screening for HCC in HC patients with cirrhosis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "HJV is a GPI-anchored glycoprotein; glycosylation is required for function.", "mechanism": "HJV mutations cause juvenile hemochromatosis via hepcidin deficiency.", "protein": "Hemojuvelin (HJV)", "protein_enriched": { "function": "Acts as a bone morphogenetic protein (BMP) coreceptor (PubMed:18976966). Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis (PubMed:18976966)", "gene_name": "HJV", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6ZVN8" }, "relationship_type": "causal", "source_pmcid": "PMC11242024" }, { "confidence": "high", "disease": "Hemochromatosis", "glycan_involvement": "Ferritin is glycosylated; glycosylation affects serum stability.", "mechanism": "Serum ferritin is elevated in HC and used to assess iron stores and prognosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242024" }, { "confidence": "medium", "disease": "Porphyria cutanea tarda", "glycan_involvement": "HFE glycosylation may modulate protein interactions in hepatocytes.", "mechanism": "HFE mutations increase risk of PCT due to hepatic iron overload.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "risk factor", "source_pmcid": "PMC11242024" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "VWF contains 12 N- and 10 O-linked oligosaccharide chains; glycosylation affects multimerization, stability, and exposure of functional epitopes.", "mechanism": "Deficiency or dysfunction of VWF impairs platelet adhesion and aggregation at sites of vascular injury, leading to bleeding tendency.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "thrombotic disorders", "glycan_involvement": "Glycosylation modulates VWF multimer size and domain accessibility, influencing thrombogenic potential.", "mechanism": "Excessive VWF multimerization or exposure of cryptic binding sites under high shear can promote platelet aggregation and thrombosis.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Altered glycosylation patterns can affect VWF clearance and function, impacting biomarker reliability.", "mechanism": "VWF plasma levels and multimer structure are diagnostic markers for von Willebrand disease.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242059" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Therapeutic VWF retains native glycosylation, essential for function and stability.", "mechanism": "Replacement therapy with plasma-derived VWF is used to treat bleeding episodes.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "thrombotic disorders", "glycan_involvement": "Glycosylation influences multimer assembly and susceptibility to proteolysis.", "mechanism": "High-molecular-weight VWF multimers are associated with increased risk of thrombosis.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "von Willebrand disease", "glycan_involvement": "Glycosylation in these domains may affect folding and mechanical properties.", "mechanism": "Mutations or structural defects in A1\u2013A3 and C1\u2013C6 domains reduce cryptic extensibility, impairing platelet binding.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "thrombotic disorders", "glycan_involvement": "Glycosylation may stabilize domain structure and modulate reduction susceptibility.", "mechanism": "Partial reduction of disulfide bonds in C4 domain increases flexibility and platelet accessibility, potentially promoting thrombosis.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "N-glycosylation near A1 domain affects epitope exposure and receptor interaction.", "mechanism": "Defective exposure of A1 domain impairs GPIb\u03b1 binding, leading to bleeding.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "thrombotic disorders", "glycan_involvement": "Glycosylation near A2 domain modulates accessibility to protease.", "mechanism": "Mechanical unfolding of A2 domain exposes cleavage site for ADAMTS13, regulating VWF size and thrombogenicity.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "medium", "disease": "von Willebrand disease", "glycan_involvement": "Glycosylation stabilizes these domains against mechanical stress.", "mechanism": "Rupture or excessive unfolding of C1\u20136 and A1\u20133 domains under shear stress may lead to loss of VWF function.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC11242059" }, { "confidence": "high", "disease": "Binge Drinking (Children and Adolescents)", "glycan_involvement": "Reduced sialylation (increase in disialo-Tf fraction) due to impaired glycosylation.", "mechanism": "Elevated serum disialotransferrin indicates recent excessive alcohol intake.", "protein": "Transferrin (Disialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "high", "disease": "Acute Alcohol Intoxication", "glycan_involvement": "Alcohol impairs glycosylation, increasing low-sialylated isoforms.", "mechanism": "Disialotransferrin levels are significantly increased in acute alcohol intoxication.", "protein": "Transferrin (Disialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Acute Alcohol Intoxication", "glycan_involvement": "Altered sialylation profile due to alcohol-induced glycosylation disturbance.", "mechanism": "Tetrasialotransferrin is elevated in acute alcohol intoxication.", "protein": "Transferrin (Tetrasialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Binge Drinking (Boys)", "glycan_involvement": "Alcohol shifts glycosylation towards lower sialylated isoforms.", "mechanism": "Trisialotransferrin is decreased in binge drinking boys.", "protein": "Transferrin (Trisialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "high", "disease": "Chronic Alcohol Abuse", "glycan_involvement": "Chronic alcohol intake impairs glycosylation, increasing CDT isoforms.", "mechanism": "Disialotransferrin is a component of carbohydrate-deficient transferrin (CDT), a marker for chronic alcohol abuse.", "protein": "Transferrin (Disialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "high", "disease": "Chronic Alcohol Abuse", "glycan_involvement": "Alcohol reduces sialylation of transferrin N-glycans.", "mechanism": "CDT (sum of asialo-, monosialo-, and disialotransferrin) is routinely used to detect chronic alcohol abuse.", "protein": "Transferrin (Carbohydrate-deficient transferrin, CDT)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Alcohol-related Liver Disease", "glycan_involvement": "Impaired glycosylation/sialylation in liver disease.", "mechanism": "Altered transferrin glycosylation profile is associated with liver dysfunction due to alcohol.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Binge Drinking (Girls)", "glycan_involvement": "Greater alcohol-induced impairment of glycosylation in females.", "mechanism": "Disialotransferrin is significantly increased in binge drinking girls, reflecting higher susceptibility.", "protein": "Transferrin (Disialotransferrin isoform)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Binge Drinking (Children and Adolescents)", "glycan_involvement": "Alcohol affects both quantity and glycosylation of transferrin.", "mechanism": "Total transferrin concentration is elevated in binge drinking youth.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "medium", "disease": "Alcohol-related Disorders", "glycan_involvement": "Alcohol decreases activity of glycosyltransferases and increases sialidase activity.", "mechanism": "Increase in low-sialylated transferrin isoforms reflects alcohol-induced glycosylation disturbance.", "protein": "Transferrin (Low-sialylated isoforms)", "relationship_type": "biomarker", "source_pmcid": "PMC11242074" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects aggregation and clearance.", "mechanism": "Extracellular accumulation forms senile plaques, leading to neurodegeneration.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC11242094" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation of APP influences A\u03b2 formation in retina.", "mechanism": "A\u03b2 detected in drusen deposits; promotes inflammation and RPE dysfunction.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "CFH binds glycosaminoglycans; glycosylation modulates function.", "mechanism": "CFH variants (Y402H) reduce binding to heparan sulfate proteoglycans, impairing complement regulation and promoting drusen formation.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ApoE glycosylation affects lipid binding and A\u03b2 interaction.", "mechanism": "APOE \u03b54 allele increases risk via impaired A\u03b2 clearance and aggregation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation modulates ApoE function in retinal lipid metabolism.", "mechanism": "APOE \u03b52 increases AMD risk; \u03b54 is protective against wet AMD.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/protective", "source_pmcid": "PMC11242094" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "EFEMP1 is a matrix glycoprotein; glycosylation affects ECM interactions.", "mechanism": "Mutant EFEMP1 accumulates between RPE and drusen, promoting macular damage.", "protein": "Fibulin 3 (EFEMP1)", "protein_enriched": { "function": "Component of the primary cilium that controls cilium formation and length (PubMed:31712586). May function within retrograde intraflagellar transport (IFT)-associated pathways to remove signaling prote", "gene_name": "ERICH3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q5RHP9" }, "relationship_type": "causal", "source_pmcid": "PMC11242094" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "C3 glycosylation modulates complement activity.", "mechanism": "C3 variants increase complement activation, contributing to inflammation and drusen formation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "CFI is glycosylated; glycosylation affects protease activity.", "mechanism": "CFI variants impair complement regulation, increasing AMD risk.", "protein": "Complement Factor I (CFI)", "protein_enriched": { "function": "Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha", "gene_name": "CFI", "glycan_count": 85, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G11911BT", "G22140GZ", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G37399XV", "G40574BA", "G41071NU", "G41247ZX", "G42124LM", "G45395BF", "G46503DX", "G48414YA", "G50045TK", "G51653BI", "G52527GH", "G59626AS", "G62765YT", "G65184UU", "G66538GV", "G70232NH", "G70619PT", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G87661QW", "G90659AW", "G92050GC", "G95865ZB", "G08293MJ", "G11629QQ", "G15169WU", "G15664MX", "G22310AV", "G23863VK", "G27947YN", "G43669FQ", "G45495MK", "G47518TP", "G56518TU", "G61256FT", "G75983OB", "G77669RF", "G83555HU", "G84452RH", "G85144OK", "G88374WZ", "G92551JA", "G94470IW", "G94917XT", "G10846ZT", "G31986NC", "G37995HC", "G72747WU", "G82830MN", "G86880BF", "G24528MX", "G39188ZX", "G45504EY", "G49329XU", "G57317CE", "G57776ZU", "G63041LO", "G70888PK", "G71569SN", "G80586MF", "G90575OW", "G92406TI", "G47737VJ", "G32788FZ", "G56784JY", "G73430PD", "G49108TO" ], "uniprot_id": "P05156" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "medium", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Glycosylation required for inhibitory function.", "mechanism": "SERPING1 regulates complement activation; variants predispose to AMD.", "protein": "SERPING1 (C1 inhibitor)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation and toxicity.", "mechanism": "Hyperphosphorylated and O-glycosylated tau forms neurofibrillary tangles, driving neurodegeneration.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242094" }, { "confidence": "medium", "disease": "Early Allograft Dysfunction (EAD)", "glycan_involvement": "N-glycosylation required for complement function and stability.", "mechanism": "Elevated serum C3a correlates with graft steatosis and EAD occurrence via complement activation.", "protein": "C3a", "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Early Allograft Dysfunction (EAD)", "glycan_involvement": "N-glycosylation required for complement function and stability.", "mechanism": "Elevated serum C5a correlates with graft steatosis and EAD occurrence via complement activation.", "protein": "C5a", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11453" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "high", "disease": "Ischemia\u2013Reperfusion Injury (IRI)", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune interactions.", "mechanism": "ICAM-1 mediates neutrophil adhesion to LSECs, promoting inflammation and tissue injury.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11242128" }, { "confidence": "high", "disease": "Graft Fibrosis", "glycan_involvement": "Glycosylation essential for ligand binding and platelet activation.", "mechanism": "P-selectin upregulation activates platelets, leading to thrombosis and HSC-dependent fibrosis.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Primary Nonfunction (PNF)", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "Elevated CRP is associated with inflammation and predicts PNF.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Primary Nonfunction (PNF)", "glycan_involvement": "Glycosylation influences albumin half-life and function.", "mechanism": "Low albumin at transplant predicts PNF; reflects liver synthetic dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Early Allograft Dysfunction (EAD)", "glycan_involvement": "N-glycosylation modulates receptor shedding and immune signaling.", "mechanism": "Elevated sCD163 reflects macrophage activation and correlates with EAD.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Early Allograft Dysfunction (EAD)", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Decreased Factor V on POD1 is associated with EAD, reflecting impaired coagulation.", "protein": "Factor V", "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "medium", "disease": "Primary Graft Dysfunction (PGD)", "glycan_involvement": "N-glycosylation affects enzyme stability and activity.", "mechanism": "Lower TAFI levels are associated with graft dysfunction, indicating impaired fibrinolysis.", "protein": "Thrombin-activatable fibrinolysis inhibitor (TAFI)", "protein_enriched": { "function": "Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by", "gene_name": "CPB2", "glycan_count": 40, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G10486CT", "G50045TK", "G00912UN", "G06247RL", "G08918WF", "G14547CB", "G22768VO", "G45526EA", "G56518TU", "G70232NH", "G70888PK", "G80075MS", "G81315DD", "G05962QB", "G06290IR", "G10019LZ", "G11115RO", "G11629QQ", "G12793SR", "G13910DJ", "G15169WU", "G22310AV", "G27947YN", "G37818NZ", "G47518TP", "G48414YA", "G52527GH", "G53075ES", "G62461SM", "G63040RU", "G70894RY", "G75983OB", "G77669RF", "G81637OR", "G84452RH", "G86880BF", "G90659AW", "G92081HT", "G93656SY", "G99679NM" ], "uniprot_id": "Q96IY4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "high", "disease": "Primary Nonfunction (PNF)", "glycan_involvement": "Altered N-glycosylation pattern reflects severe graft injury.", "mechanism": "Elevated NGA2F glycan in perfusate predicts PNF with high accuracy.", "protein": "NGA2F", "relationship_type": "biomarker", "source_pmcid": "PMC11242128" }, { "confidence": "high", "disease": "Proteinuria", "glycan_involvement": "Osteopontin is a secreted glycoprotein; glycosylation affects secretion and function.", "mechanism": "Reduced secretion in podocytes correlates with everolimus dose and proteinuria severity.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Tubulointerstitial fibrosis", "glycan_involvement": "Glycosylation modulates osteopontin's interaction with cells and ECM.", "mechanism": "Upregulation associated with macrophage accumulation and fibrosis.", "protein": "Osteopontin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "high", "disease": "Kidney fibrosis", "glycan_involvement": "No direct glycan involvement; PLK1 is not a glycoprotein.", "mechanism": "PLK1 upregulation promotes myofibroblast activation and fibrosis via TGF-\u03b21 pathway.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "causal", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Proteinuria", "glycan_involvement": "No direct glycan involvement.", "mechanism": "PLK1 activation may stimulate autophagy, protecting podocytes from everolimus-induced damage.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "high", "disease": "Proteinuria", "glycan_involvement": "Nephrin is N-glycosylated; glycosylation is essential for slit diaphragm function.", "mechanism": "Downregulation after mTOR-I treatment correlates with podocyte injury and proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Proteinuria", "glycan_involvement": "Potential glycosylation may affect membrane localization.", "mechanism": "Downregulation after mTOR-I treatment impairs podocyte structure, leading to proteinuria.", "protein": "Podocin", "protein_enriched": { "function": "Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton", "gene_name": "NPHS2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP85" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Proteinuria", "glycan_involvement": "Potential glycosylation may modulate protein interactions.", "mechanism": "Reduced expression after mTOR-I treatment disrupts slit diaphragm integrity.", "protein": "CD2AP", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242170" }, { "confidence": "high", "disease": "Glomerulosclerosis", "glycan_involvement": "Cathepsin D is glycosylated; glycosylation required for lysosomal targeting.", "mechanism": "Loss in podocytes leads to autophagosome accumulation, apoptosis, and glomerulosclerosis.", "protein": "Cathepsin D", "relationship_type": "causal", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Renal injury", "glycan_involvement": "Glycosylation modulates osteopontin's protective functions.", "mechanism": "Upregulation may promote tubular regeneration and repair after injury.", "protein": "Osteopontin", "relationship_type": "protective", "source_pmcid": "PMC11242170" }, { "confidence": "medium", "disease": "Kidney fibrosis", "glycan_involvement": "Potential glycosylation may affect lysosomal function.", "mechanism": "PLK1 downregulation impairs ATP6V1A, causing lysosome damage and fibrosis.", "protein": "V-ATPase subunit ATP6V1A", "protein_enriched": { "function": "Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translo", "gene_name": "ATP6V1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P38606" }, "relationship_type": "causal", "source_pmcid": "PMC11242170" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect PAC-A binding affinity; spike is heavily glycosylated.", "mechanism": "SP4\u2122 PAC-As interact with SARS-CoV-2 spike glycoprotein, impairing attachment and entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "high", "disease": "Human coronavirus OC43 infection", "glycan_involvement": "Glycosylation may modulate PAC-A interaction; spike is glycosylated.", "mechanism": "SP4\u2122 PAC-As bind hCoV-OC43 spike glycoprotein, causing aggregation and loss of infectivity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "HA is glycosylated; PAC-As preferentially bind glycoproteins.", "mechanism": "PAC-A2 from cranberry extract interacts with HA1 domain, blocking attachment and entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "high", "disease": "Influenza B", "glycan_involvement": "Glycosylation facilitates PAC-A binding.", "mechanism": "PAC-A2 impairs HA1 function, leading to virucidal effect.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "Influenza A", "glycan_involvement": "NA is glycosylated; polyphenol binding may be glycan-dependent.", "mechanism": "Pomegranate polyphenols interact with NA glycoprotein, reducing infectivity.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "G glycoprotein is glycosylated; PAC-As may bind glycan-rich regions.", "mechanism": "SP4\u2122 inhibits RSV replication, likely via interaction with envelope glycoproteins.", "protein": "G glycoprotein", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection (PubMed:10400758, PubMed:10864656, PubMed:3655746). Interacts with host CX3CR1, the receptor", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 33, "glytoucan_ids": [], "uniprot_id": "P03423" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "Influenza A", "glycan_involvement": "BanLec is mannose-specific; targets glycan moieties.", "mechanism": "BanLec binds viral envelope glycoproteins, blocking attachment.", "protein": "BanLec", "protein_enriched": { "function": "", "gene_name": "YK3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9M5I1" }, "relationship_type": "protective", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Targets high-mannose glycans on spike.", "mechanism": "BanLec inhibits hCoV infectivity by binding spike glycoprotein glycans.", "protein": "BanLec", "protein_enriched": { "function": "", "gene_name": "YK3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9M5I1" }, "relationship_type": "protective", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Mannose-specific binding to spike glycans.", "mechanism": "Griffithsin binds spike glycoprotein, blocking viral entry.", "protein": "Griffithsin", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6Y2C5" }, "relationship_type": "protective", "source_pmcid": "PMC11242173" }, { "confidence": "medium", "disease": "Human coronavirus 229E infection", "glycan_involvement": "Spike glycoprotein is glycosylated; PAC-As may bind glycan-rich regions.", "mechanism": "SP4\u2122 inhibits hCoV-229E replication, likely via spike glycoprotein interaction.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242173" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "GPCR glycosylation affects receptor localization and function.", "mechanism": "SCFA-GPR43 signaling reduces neutrophil infiltration and inflammation.", "protein": "GPR43 (FFAR2)", "protein_enriched": { "function": "G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasi", "gene_name": "FFAR2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O15552" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242198" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "GPCR glycosylation modulates ligand binding and signaling.", "mechanism": "Butyrate-GPR109A signaling induces anti-inflammatory and tumor suppressor effects.", "protein": "GPR109A (HCA2)", "relationship_type": "protective", "source_pmcid": "PMC11242198" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "HDACs may be O-glycosylated, affecting nuclear localization.", "mechanism": "Butyrate inhibits HDAC1/2, leading to cell cycle arrest and apoptosis in CRC cells.", "protein": "HDAC1/2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "GPCR glycosylation influences receptor stability.", "mechanism": "Propionate-GPR41 signaling reduces vascular inflammation and atherosclerosis.", "protein": "GPR41 (FFAR3)", "protein_enriched": { "function": "G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasi", "gene_name": "FFAR3", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O14843" }, "relationship_type": "protective", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "IL-6R N-glycosylation modulates receptor signaling.", "mechanism": "Acetate-GPR43 signaling inhibits IL-6/JAK1/STAT3 pathway, preventing NAFLD-HCC progression.", "protein": "IL-6 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242198" }, { "confidence": "high", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Foxp3 O-glycosylation may affect stability.", "mechanism": "Butyrate enhances histone acetylation at Foxp3 locus, promoting Treg differentiation and reducing colitis.", "protein": "Foxp3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "CXCR2 N-glycosylation affects receptor trafficking.", "mechanism": "Acetate reduces CXCR2 surface expression on neutrophils, decreasing inflammation.", "protein": "CXCR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Pneumococcal infection", "glycan_involvement": "NLRP3 glycosylation may regulate inflammasome assembly.", "mechanism": "Acetate therapy eliminates NLRP3 inflammasome activation, enhancing macrophage bactericidal activity.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "protective", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "SIRT1 O-glycosylation may affect enzymatic activity.", "mechanism": "Butyrate inhibits SIRT1, suppressing mTOR/S6K1 pathway and inducing apoptosis.", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242198" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "GPCR glycosylation modulates renal signaling.", "mechanism": "Butyrate-GPR109A signaling reduces kidney inflammation and dysfunction.", "protein": "GPR109A (HCA2)", "relationship_type": "protective", "source_pmcid": "PMC11242198" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "LDL glycosylation affects its clearance and atherogenicity.", "mechanism": "Elevated LDL-C is causally linked to ASCVD risk.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC11242215" }, { "confidence": "high", "disease": "Statin-associated asthenia", "glycan_involvement": "No direct glycosylation involvement; CoQ10 is not a glycoprotein.", "mechanism": "CoQ10 supplementation improves physical performance and reduces asthenia in statin-treated older adults.", "protein": "Coenzyme Q10 (CoQ10)", "relationship_type": "protective", "source_pmcid": "PMC11242215" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "LDL glycosylation may influence statin efficacy.", "mechanism": "Statins lower LDL-C to reduce ASCVD risk.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242215" }, { "confidence": "medium", "disease": "Statin-associated muscle symptoms (SAMS)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "CoQ10 supplementation may counteract mitochondrial dysfunction induced by statins.", "protein": "Coenzyme Q10 (CoQ10)", "relationship_type": "protective", "source_pmcid": "PMC11242215" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "HDL glycosylation modulates anti-atherogenic properties.", "mechanism": "HDL-C is inversely correlated with ASCVD risk.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11242215" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "CoQ10 supplementation may reduce risk of heart failure in statin-treated patients.", "protein": "Coenzyme Q10 (CoQ10)", "relationship_type": "protective", "source_pmcid": "PMC11242215" }, { "confidence": "medium", "disease": "Statin-associated muscle symptoms (SAMS)", "glycan_involvement": "CPK is glycosylated, which may affect its stability and detection.", "mechanism": "Elevated CPK indicates muscle damage in SAMS.", "protein": "Creatine Phosphokinase (CPK)", "relationship_type": "biomarker", "source_pmcid": "PMC11242215" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "GGT glycosylation affects its enzymatic activity.", "mechanism": "Elevated GGT is associated with increased ASCVD risk.", "protein": "Gamma-Glutamyl Transferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC11242215" }, { "confidence": "low", "disease": "Statin-associated muscle symptoms (SAMS)", "glycan_involvement": "LDL glycosylation may modulate immune response and muscle symptoms.", "mechanism": "LDL composition changes may reflect statin effects and muscle symptom risk.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242215" }, { "confidence": "low", "disease": "Myalgia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "CoQ10 supplementation may reduce myalgia in some statin-treated patients.", "protein": "Coenzyme Q10 (CoQ10)", "relationship_type": "protective", "source_pmcid": "PMC11242215" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "AGEs formation via glycation of lysine/arginine residues.", "mechanism": "Non-enzymatic glycation leads to advanced glycation endproducts (AGEs) accumulation, altering collagen structure and increasing bone fragility.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and signaling.", "mechanism": "Elevated sclerostin levels inhibit Wnt signaling, reducing bone formation and increasing fracture risk.", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242219" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Secreted glycoprotein; glycosylation affects receptor binding.", "mechanism": "Increased serum OPG binds RANKL, modulating osteoclastogenesis and bone resorption.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Membrane glycoprotein; glycosylation modulates receptor interaction.", "mechanism": "RANKL promotes osteoclast differentiation and bone resorption, contributing to osteoporosis.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Heavily glycosylated; glycosylation affects enzymatic activity and substrate specificity.", "mechanism": "DPP-4 inhibitors reduce degradation of incretins, indirectly improving bone quality and reducing fracture risk.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "T1DM", "glycan_involvement": "Secreted glycoprotein; glycosylation not directly implicated in bone effects.", "mechanism": "Insulin deficiency impairs osteoblast function, reducing bone formation and mass.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11242219" }, { "confidence": "medium", "disease": "T1DM", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect secretion.", "mechanism": "Reduced amylin secretion decreases osteoblast activity and increases bone fragility.", "protein": "Amylin", "relationship_type": "causal", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Membrane glycoprotein; glycosylation affects receptor function.", "mechanism": "GLP-1 receptor agonists reduce osteoclastogenesis and bone resorption, protecting against bone loss.", "protein": "GLP-1 Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242219" }, { "confidence": "medium", "disease": "Osteomalacia", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and activity.", "mechanism": "SGLT2 inhibitors increase FGF23, leading to altered phosphate metabolism and risk of osteomalacia.", "protein": "Fibroblast Growth Factor 23 (FGF23)", "relationship_type": "causal", "source_pmcid": "PMC11242219" }, { "confidence": "medium", "disease": "T1DM", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect hormone activity.", "mechanism": "Low osteocalcin levels reflect reduced bone formation in T1DM.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242219" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation of APP affects its processing and A\u03b2 generation.", "mechanism": "APP mutations increase A\u03b2 production, leading to amyloid plaque formation and neurodegeneration.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11242231" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Altered glycosylation may modulate APP cleavage and A\u03b2 oligomerization.", "mechanism": "APP mutations and A\u03b2 accumulation increase neuronal excitability and seizure risk.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11242231" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APOE is N-glycosylated; glycosylation modulates receptor binding and A\u03b2 interaction.", "mechanism": "APOE\u03b54 allele increases AD risk by impairing A\u03b2 clearance and affecting synaptic function.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242231" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation may influence APOE's neuroprotective and inflammatory roles.", "mechanism": "APOE\u03b54 increases risk of late-onset epilepsy via effects on neuronal excitability and inflammation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "risk factor", "source_pmcid": "PMC11242231" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "TREM2 is N-glycosylated; glycosylation is critical for surface expression and function.", "mechanism": "TREM2 variants impair microglial A\u03b2 clearance, increasing AD risk.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11242231" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation required for TREM2 function in microglia.", "mechanism": "TREM2 deficiency increases seizure susceptibility by reducing microglial regulation of hyperexcitability.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC11242231" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CLU is heavily N-glycosylated, affecting its chaperone activity.", "mechanism": "CLU modulates A\u03b2 aggregation and clearance; genetic variants increase AD risk.", "protein": "Clusterin (CLU)", "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC11242231" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation regulates BACE1 stability and activity.", "mechanism": "BACE1 cleaves APP to generate A\u03b2, driving AD pathology.", "protein": "Beta-secretase 1 (BACE1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11242231" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation modulates BACE1 trafficking and function.", "mechanism": "BACE1 cleaves \u03b22/\u03b24 subunits of voltage-gated Na+ channels, increasing neuronal hyperexcitability.", "protein": "Beta-secretase 1 (BACE1)", "relationship_type": "causal", "source_pmcid": "PMC11242231" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "A\u03b2 glycosylation status may affect aggregation and toxicity.", "mechanism": "A\u03b2 oligomers increase glutamate release and neuronal excitability, promoting seizures.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242231" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "N-glycosylation is essential for EPO stability and activity.", "mechanism": "EPO stimulates erythroid stem cell differentiation and red blood cell production; deficiency causes anemia in CKD.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242251" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation required for EPO secretion and function.", "mechanism": "CKD leads to reduced EPO production by renal fibroblasts, causing anemia.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "causal", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects transferrin half-life and iron binding.", "mechanism": "Transferrin levels predict iron availability for erythropoiesis; low transferrin linked to anemia.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242251" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "High hepcidin in CKD blocks iron export, causing defective iron utilization and anemia.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation required for stability and ferroxidase activity.", "mechanism": "Ceruloplasmin promotes iron mobilization; induced by HIF-PH inhibitors to improve iron utilization.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "TfR mediates cellular iron uptake; upregulated by HIF-PH inhibitors to enhance erythropoiesis.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Thromboembolic complications", "glycan_involvement": "N-glycosylation modulates vWF multimerization and function.", "mechanism": "High-dose ESAs increase vWF release, promoting platelet aggregation and thrombosis.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Thromboembolic complications", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "High-dose ESAs induce E-selectin expression, enhancing platelet activity and thrombosis risk.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC11242251" }, { "confidence": "medium", "disease": "Thromboembolic complications", "glycan_involvement": "Glycosylation required for function.", "mechanism": "High-dose ESAs induce P-selectin expression, increasing platelet activation and thrombotic risk.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242251" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects EPO receptor binding and half-life.", "mechanism": "EPO and HIF-PH inhibitors may stimulate angiogenesis, potentially increasing cancer risk.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "risk_factor", "source_pmcid": "PMC11242251" }, { "confidence": "high", "disease": "Systemic juvenile idiopathic arthritis (SJIA)", "glycan_involvement": "Glycosylation affects receptor stability and drug binding.", "mechanism": "Targeted by tocilizumab to reduce inflammation in SJIA.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242299" }, { "confidence": "high", "disease": "Systemic juvenile idiopathic arthritis (SJIA)", "glycan_involvement": "Glycosylation modulates receptor function and immune recognition.", "mechanism": "Targeted by anakinra/canakinumab to block IL-1 signaling in SJIA.", "protein": "Interleukin-1 receptor (IL-1R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242299" }, { "confidence": "high", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "KL-6 is a mucin-type glycoprotein; glycosylation is essential for its detection and function.", "mechanism": "KL-6 is elevated in serum after alveolar type II cell damage, indicating ILD.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation affects ferritin secretion and stability.", "mechanism": "Serum ferritin is markedly elevated in MAS, reflecting hyperinflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Systemic juvenile idiopathic arthritis (SJIA)", "glycan_involvement": "Glycosylation status may affect albumin half-life and function.", "mechanism": "Hypoalbuminemia is a predictor of severe SJIA and respiratory involvement.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation may influence secretion and activity.", "mechanism": "IL-18 overproduction drives MAS and is a therapeutic target.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "IFN\u03b3 hyperactivation is central to MAS pathogenesis.", "protein": "Gamma-interferon (IFN\u03b3)", "relationship_type": "causal", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)", "glycan_involvement": "Glycosylation of HLA molecules affects antigen presentation.", "mechanism": "HLA-DRB1*15 allele increases risk of DRESS in SJIA patients treated with biologics.", "protein": "HLA-DRB1*15", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 56, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02815KT", "G03644CB", "G04657PL", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G11314AS", "G13131HA", "G14972EH", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31852PQ", "G35541EV", "G36379GD", "G39471UU", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G47644PP", "G50856PC", "G57776ZS", "G58087IP", "G60834IK", "G62765YT", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G76295SF", "G77669RF", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G83646BJ", "G86880BF", "G87661QW", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G98611JV" ], "uniprot_id": "P01911" }, "relationship_type": "risk_factor", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "Altered glycosylation may contribute to immunogenicity.", "mechanism": "Hypersensitivity reactions to IL-6R blockers (tocilizumab) are associated with ILD development.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "causal", "source_pmcid": "PMC11242299" }, { "confidence": "medium", "disease": "Systemic juvenile idiopathic arthritis (SJIA)", "glycan_involvement": "Glycosylation is required for KL-6 antigenicity.", "mechanism": "KL-6 can be used to monitor lung involvement in SJIA.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242299" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MHC II glycosylation affects peptide binding and stability.", "mechanism": "Increases affinity for MBP epitopes, promoting autoantigen presentation and T cell activation.", "protein": "HLA-DRB1*15:01", "relationship_type": "causal", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates MHC II surface expression.", "mechanism": "Associated with increased susceptibility via altered antigen presentation.", "protein": "HLA-DRB1*15:01", "relationship_type": "risk/causal", "source_pmcid": "PMC11242320" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MHC II glycosylation influences immune cell interactions.", "mechanism": "Promotes M1 macrophage polarization and high-affinity MBP binding.", "protein": "HLA-DRB1*04:01", "relationship_type": "causal", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation affects antigen presentation efficiency.", "mechanism": "Associated with increased risk and acute relapses in pediatric MS.", "protein": "HLA-DRB1*03:01", "relationship_type": "risk/causal", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may modulate peptide discrimination.", "mechanism": "Lower affinity for MBP peptides, reducing autoimmunity.", "protein": "HLA-DRB1*01:01", "relationship_type": "protective", "source_pmcid": "PMC11242320" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "PTMs may affect glycan exposure and immune recognition.", "mechanism": "Post-translational modifications (citrullination, acetylation) increase MHC II affinity, driving autoimmunity.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "causal/autoantigen", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation required for surface expression and function.", "mechanism": "Costimulatory molecule for T cell activation; targeted by therapies to modulate immune response.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation essential for function.", "mechanism": "Costimulatory molecule for T cell activation; involved in APC-T cell interaction.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "Regulates immune cell migration across BBB; upregulated in neuroinflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242320" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "N-glycosylation affects ligand binding.", "mechanism": "Facilitates leukocyte adhesion and migration into CNS during inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242320" }, { "confidence": "high", "disease": "COVID-19-associated CNS involvement", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP indicates systemic inflammation and cytokine storm, associated with increased risk of CNS complications.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "High CRP levels correlate with disease severity and poor outcomes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Platelet glycoproteins mediate adhesion and aggregation; glycosylation is essential for function.", "mechanism": "Reduced platelet count is linked to CNS involvement and mortality in severe COVID-19.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Glycosylation regulates platelet receptor activity.", "mechanism": "Thrombocytopenia and platelet dysfunction contribute to neurovascular events.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "Lymphopenia", "glycan_involvement": "Glycosylation affects lymphocyte trafficking and immune response.", "mechanism": "Low lymphocyte count is an independent risk factor for CNS involvement in severe COVID-19.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11242379" }, { "confidence": "high", "disease": "In-hospital mortality", "glycan_involvement": "Glycosylation influences CRP's interaction with immune cells.", "mechanism": "High CRP predicts increased risk of death in severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "In-hospital mortality", "glycan_involvement": "Glycosylation is critical for platelet survival and function.", "mechanism": "Low platelet count is associated with higher mortality.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "COVID-19-associated CNS involvement", "glycan_involvement": "Glycosylation modulates lymphocyte activation and CNS infiltration.", "mechanism": "Lymphopenia is linked to increased risk of neurological complications.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "medium", "disease": "COVID-19 encephalopathy", "glycan_involvement": "CRP glycosylation affects its CNS penetration and inflammatory potential.", "mechanism": "Elevated CRP is associated with encephalopathy in severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "low", "disease": "COVID-19-associated headache", "glycan_involvement": "Glycosylation impacts platelet-endothelial interactions.", "mechanism": "Thrombocytopenia may contribute to headache via microvascular dysfunction.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11242379" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "VCAM-1 is a heavily glycosylated adhesion molecule; glycosylation modulates its cell surface expression and function.", "mechanism": "VCAM-1 is elevated in HIV/HCV coinfection, indicating endothelial activation and increased risk of CVD.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "IP-10 is glycosylated, which affects its stability and chemotactic activity.", "mechanism": "IP-10 levels are elevated in HIV/HCV coinfection, reflecting ongoing hepatic necro-inflammatory activity.", "protein": "IP-10", "relationship_type": "biomarker", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Immune Activation/Exhaustion", "glycan_involvement": "CD8 is glycosylated; glycosylation affects T cell receptor interactions and immune signaling.", "mechanism": "Persistent elevation and exhaustion of CD8+ T cells in HIV/HCV coinfection contribute to immune dysregulation.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Immune Activation/Exhaustion", "glycan_involvement": "CD4 glycosylation modulates HIV binding and immune function.", "mechanism": "CD4+ T cell counts recover after HCV clearance, indicating improved immune restoration.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242478" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "IFN-\u03b1 is glycosylated, affecting its stability and receptor binding.", "mechanism": "IFN-\u03b1 therapy induces proinflammatory and immunomodulatory effects, confounding comorbidity risk in older studies.", "protein": "Interferon-alpha (IFN-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates HIV entry and chronic immune activation.", "protein": "HIV-1 Envelope Glycoprotein (gp120)", "relationship_type": "causal", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "HCV Infection", "glycan_involvement": "N-glycosylation of E2 modulates receptor binding and immune escape.", "mechanism": "E2 mediates HCV entry and immune evasion.", "protein": "HCV Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation regulates VCAM-1 function in inflammation.", "mechanism": "VCAM-1 elevation correlates with hepatic necro-inflammatory activity in HIV/HCV coinfection.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation affects IP-10 chemotactic activity.", "mechanism": "IP-10 recruits immune cells to the liver, promoting inflammation and fibrosis.", "protein": "IP-10", "relationship_type": "biomarker", "source_pmcid": "PMC11242478" }, { "confidence": "medium", "disease": "Non-AIDS Cancer", "glycan_involvement": "Glycosylation modulates CD8+ T cell function and tumor surveillance.", "mechanism": "Persistent CD8+ T cell activation/exhaustion may predispose to non-AIDS cancer in HIV/HCV coinfection.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC11242478" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CD14 is N-glycosylated, which affects its stability and receptor interactions.", "mechanism": "Cleaved soluble CD14 (presepsin) increases in blood during bacterial infection, reflecting immune activation.", "protein": "CD14 (Presepsin)", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TREM-1 is N-glycosylated, influencing cell surface expression and ligand binding.", "mechanism": "Soluble TREM-1 is released during infection, amplifies inflammation; blockade (nangibotide) modulates immune response.", "protein": "TREM-1 (sTREM-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "uPAR is heavily N-glycosylated, affecting its shedding and function.", "mechanism": "Soluble uPAR increases in plasma during systemic inflammation and correlates with sepsis severity.", "protein": "uPAR (suPAR)", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CD64 is N-glycosylated, modulating Fc receptor function.", "mechanism": "Neutrophil CD64 expression increases rapidly in bacterial sepsis, serving as a diagnostic marker.", "protein": "CD64", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "PTX3 is N-glycosylated, which is essential for ligand binding and complement activation.", "mechanism": "PTX3 is an acute-phase protein elevated in sepsis, reflecting innate immune activation and organ damage.", "protein": "Pentraxin 3 (PTX3)", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "ADM glycosylation status debated; if present, may affect peptide stability.", "mechanism": "ADM levels rise in septic shock; bio-ADM modulates vascular permeability and is targeted by adrecizumab.", "protein": "Adrenomedullin (ADM)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis-associated coagulopathy/DIC", "glycan_involvement": "Ang2 is N-glycosylated, affecting secretion and receptor binding.", "mechanism": "Ang2 increases vascular permeability and is elevated in sepsis-associated DIC.", "protein": "Angiopoietin-2 (Ang2)", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Not glycosylated.", "mechanism": "Released from neutrophils during infection, calprotectin amplifies inflammation and is a sensitive sepsis marker.", "protein": "Calprotectin (S100A8/A9)", "relationship_type": "biomarker", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury", "glycan_involvement": "Not glycosylated.", "mechanism": "HMGB1 is released during cell death, acts as a DAMP, and drives late inflammation and organ injury.", "protein": "High Mobility Group Box 1 (HMGB1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Sepsis/Septic shock", "glycan_involvement": "IL-6 is N-glycosylated, which affects secretion and receptor binding.", "mechanism": "IL-6 is rapidly induced in sepsis, drives acute-phase response; blockade reduces mortality in some contexts.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242529" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects aggregation and clearance; EVs may carry glycosylated forms.", "mechanism": "Elevated levels in brain-derived exosomal proteins in blood and CSF reflect AD pathology.", "protein": "Amyloid-\u03b242 (A\u03b2-42)", "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation and EV sorting.", "mechanism": "Increased phosphorylated tau in EVs correlates with AD diagnosis and progression.", "protein": "Tau (total-tau, p-T181-tau, p-S396-tau)", "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation influences \u03b1-syn aggregation and EV packaging.", "mechanism": "EV-associated \u03b1-syn levels are elevated in plasma and saliva, reflecting PD severity and progression; EVs may mediate spread.", "protein": "Alpha-synuclein (\u03b1-syn)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect DJ-1 stability and secretion in EVs.", "mechanism": "Elevated DJ-1 in EVs from plasma and urine in PD patients.", "protein": "DJ-1", "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may regulate LRRK2 activity and EV association.", "mechanism": "High levels in urine exosomes in idiopathic PD.", "protein": "LRRK2 (Ser(P)-1292)", "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect neurogranin stability and EV sorting.", "mechanism": "Higher levels in CSF/plasma, lower in neuronal-derived EVs; predictive for AD.", "protein": "Neurogranin", "protein_enriched": { "function": "Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium (By similarity)", "gene_name": "NRGN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92686" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates SNAP25 function and EV inclusion.", "mechanism": "EV-associated SNAP25 predicts AD years before cognitive impairment.", "protein": "SNAP25", "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "O-glycosylation affects MBP immunogenicity and EV release.", "mechanism": "EVs contain MBP, reflecting demyelination and disease activity.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242541" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "Glycosylation may regulate TDP-43 aggregation and EV sorting.", "mechanism": "Elevated TDP-43 in EVs from CSF, plasma, and serum in ALS; involved in disease spread.", "protein": "TDP-43", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242541" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "Glycosylation may affect SOD1 stability and EV packaging.", "mechanism": "Elevated SOD1 in EVs in ALS; associated with disease pathology.", "protein": "SOD1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242541" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ApoE is N-glycosylated, which affects its stability and receptor interactions.", "mechanism": "ApoE deficiency leads to impaired clearance of LDL cholesterol, promoting plaque formation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC11242574" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDLR is N-glycosylated, essential for proper folding and function.", "mechanism": "LDLR deficiency impairs LDL uptake, increasing plasma cholesterol and atherosclerotic risk.", "protein": "Low-Density Lipoprotein Receptor (LDLR)", "relationship_type": "causal", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 is linked to inflammatory processes in atherosclerosis and other diseases.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and function.", "mechanism": "CRP levels reflect systemic inflammation and disease activity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "GAGs are glycosylated polysaccharides with anti-inflammatory effects.", "mechanism": "Cricket-derived GAGs reduce CRP and inflammatory biomarkers, suppressing arthritis.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "GAGs interact with cytokines and growth factors via glycan chains.", "mechanism": "Cricket GAGs modulate IL-6 and PGE2, reducing inflammation and plaque formation.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "protective", "source_pmcid": "PMC11242574" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "ALT is glycosylated, which may affect its secretion and stability.", "mechanism": "Elevated ALT indicates hepatic injury and is associated with oxidative stress in atherosclerosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "IL-6 glycosylation modulates its receptor binding and activity.", "mechanism": "IL-6 is a pro-inflammatory cytokine elevated in atherosclerosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242574" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "GAGs' glycan chains mediate anti-inflammatory and hepatoprotective effects.", "mechanism": "Cricket GAGs reduce ALT and AST, improving hepatocyte metabolic activity.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "protective", "source_pmcid": "PMC11242574" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycan structure is essential for anti-inflammatory activity.", "mechanism": "Insect-derived GAGs and peptides reduce inflammation and improve metabolic status.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "protective", "source_pmcid": "PMC11242574" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Target of autoantibodies (a\u03b22GPI) leading to thrombosis, impaired decidualization, and placental damage.", "protein": "Beta-2 glycoprotein I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "high", "disease": "Chronic endometritis", "glycan_involvement": "Heparan sulfate glycosaminoglycan chains mediate cell adhesion and migration.", "mechanism": "CD138+ plasma cells are diagnostic for chronic endometritis in endometrial tissue.", "protein": "CD138 (syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Diabetes (LADA/Type 1)", "glycan_involvement": "N-glycosylation required for receptor function and signaling.", "mechanism": "Insulin resistance represses IGF-1R, impairing endometrial receptivity and decidualization.", "protein": "IGF-1 receptor", "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Diabetes (LADA/Type 1)", "glycan_involvement": "Potential O-glycosylation modulates stability and signaling.", "mechanism": "IRS2 downregulation impairs insulin signaling, affecting uterine gene expression and glucose utilization during decidualization.", "protein": "Insulin receptor substrate 2 (IRS2)", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:25879", "gene_name": "IRS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4H2" }, "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "N-glycosylation critical for VEGF secretion and receptor binding.", "mechanism": "APAs inhibit VEGF, blocking angiogenesis and impairing decidualization.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242609" }, { "confidence": "high", "disease": "Thyroid autoimmunity", "glycan_involvement": "N-glycosylation influences antigenicity and autoantibody recognition.", "mechanism": "Anti-TPO antibodies indicate thyroid autoimmunity, associated with reduced fertility and altered endometrial immunity.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Chronic endometritis", "glycan_involvement": "Sialyl Lewis X glycan binding essential for leukocyte adhesion.", "mechanism": "Upregulated in CE, mediates B-cell extravasation and migration into endometrium.", "protein": "CD62E (E-selectin)", "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Chronic endometritis", "glycan_involvement": "Glycosylation may affect secretion and receptor interaction.", "mechanism": "Chemokine upregulated in CE, recruits B cells to endometrial tissue.", "protein": "CXCL13", "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Adenomyosis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated IL-6 promotes pro-inflammatory state, impairs decidualization and endometrial receptivity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation modulates receptor binding and bioactivity.", "mechanism": "Increased TNF-\u03b1 drives inflammation, pain, and impaired implantation.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242609" }, { "confidence": "high", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "N-glycosylation modulates receptor stability and signaling.", "mechanism": "Promotes tumor aggressiveness and metastasis via cell signaling; overexpression linked to poor prognosis.", "protein": "ERBB2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "N-glycosylation affects cell-matrix interactions.", "mechanism": "Facilitates angiogenesis and cell adhesion, promoting metastatic dissemination.", "protein": "VTN", "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "Glycosylation influences receptor trafficking and ligand binding.", "mechanism": "Associated with hypoxic response and lymphatic spread of tumor cells.", "protein": "ACKR3", "protein_enriched": { "function": "Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting ins", "gene_name": "ACKR3", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P25106" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and signaling.", "mechanism": "Involved in TGF-beta signaling and EMT, facilitating tumor cell migration.", "protein": "LEFTY2", "protein_enriched": { "function": "Plays a role in the apoptotic process and has a pro-apoptotic activity", "gene_name": "IFI27L2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2X8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "Glycosylation may modulate enzyme activity and localization.", "mechanism": "Promotes tumor growth, angiogenesis, and metastasis.", "protein": "PTGS2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects secretion and function.", "mechanism": "Promotes cell growth, survival, and resistance to apoptosis.", "protein": "REG1A", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05444" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Potential O-glycosylation may affect protein stability.", "mechanism": "Correlates with advanced tumor stage and poor survival; involved in MDM2-p53/p21 pathway.", "protein": "SPRR2B", "protein_enriched": { "function": "Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All t", "gene_name": "SPRR1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35321" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "Potential O-glycosylation may affect structural properties.", "mechanism": "High levels predict worse survival; involved in cornified envelope formation.", "protein": "SPRR2E", "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Potential O-glycosylation may affect protein function.", "mechanism": "Overexpression linked to early-stage disease and progression.", "protein": "SPRR2D", "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Breast cancer with axillary lymph node metastasis (ALNM)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect activity.", "mechanism": "Involved in IL6/JAK/STAT3 signaling, promoting inflammation and metastasis.", "protein": "INHBE", "relationship_type": "biomarker", "source_pmcid": "PMC11242629" }, { "confidence": "medium", "disease": "Intensive Care Unit Acquired Weakness (ICUAW)", "glycan_involvement": "Albumin glycosylation affects its stability and function.", "mechanism": "Lower albumin levels are a risk factor for ICUAW in ECMO patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "CPK glycosylation may affect serum clearance.", "mechanism": "Elevated CPK indicates muscle damage/rhabdomyolysis; monitored after NMES.", "protein": "Creatine phosphokinase (CPK)", "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "AST glycosylation influences enzyme activity.", "mechanism": "AST elevation signals liver injury; monitored post-NMES.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "ALT glycosylation modulates enzyme stability.", "mechanism": "ALT decrease post-NMES may indicate improved liver status.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "LDH glycosylation affects tissue distribution.", "mechanism": "LDH elevation is a marker of muscle/liver injury; unchanged after NMES.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Cell surface glycoproteins mediate EPC homing.", "mechanism": "NMES promotes EPCs, aiding endothelial repair in SIRS/sepsis.", "protein": "Endothelial progenitor cells (EPCs)", "relationship_type": "protective", "source_pmcid": "PMC11242632" }, { "confidence": "low", "disease": "Edema", "glycan_involvement": "VEGF glycosylation regulates receptor binding.", "mechanism": "VEGF increases vascular permeability, contributing to edema.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC11242632" }, { "confidence": "medium", "disease": "Gram-negative septicemia", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "Immunoglobulins mediate immune response in septicemia.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC11242632" }, { "confidence": "low", "disease": "Kidney dysfunction", "glycan_involvement": "N-glycosylation affects transferrin clearance.", "mechanism": "Altered transferrin glycosylation may reflect renal injury.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242632" }, { "confidence": "low", "disease": "Cardiogenic shock", "glycan_involvement": "Glycosylation modulates fibrinogen function.", "mechanism": "Fibrinogen involved in coagulation abnormalities in shock.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC11242632" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Non-enzymatic glycation of proteins (AGE formation).", "mechanism": "AGEs accumulate in glomerular matrix, causing capillary occlusion and sclerosis.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "Non-enzymatic glycation of collagen/elastin.", "mechanism": "AGEs cause basal membrane thickening and vascular dysfunction in retinal capillaries.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "Binding of glycated proteins to RAGE.", "mechanism": "AGE-RAGE interaction triggers inflammatory cytokine production.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycation at terminal amino groups.", "mechanism": "Glycated hemoglobin (HbA1c) used to monitor glycemic control.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Non-enzymatic glycation.", "mechanism": "Glycation reduces RBC deformability and increases endothelial adherence.", "protein": "Spectrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability.", "mechanism": "Suppresses macrophage function and inflammation, decreases insulin resistance.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "Secreted glycoprotein; glycosylation affects function.", "mechanism": "Elevated leptin promotes pro-inflammatory responses.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Secreted glycoprotein; glycosylation affects activity.", "mechanism": "Resistin promotes endothelial dysfunction, chronic inflammation, and thrombosis.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Hemodialysis-induced Immune Dysfunction", "glycan_involvement": "Lectin pathway activation via glycan recognition.", "mechanism": "MBL binds to dialysis membranes, activating complement and inflammation.", "protein": "MBL", "relationship_type": "causal", "source_pmcid": "PMC11242658" }, { "confidence": "medium", "disease": "Hemodialysis-induced Immune Dysfunction", "glycan_involvement": "Glycosylation required for inhibitory function.", "mechanism": "Clusterin acts as complement inhibitor; adsorption by membranes reduces protection.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "protective", "source_pmcid": "PMC11242658" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects clearance and receptor binding.", "mechanism": "Increased LDL after DAA/HAART therapy is associated with higher cardiovascular risk in HIV/HCV patients.", "protein": "LDL", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242662" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL glycosylation modulates anti-atherogenic properties.", "mechanism": "HDL levels remained unchanged post-therapy; higher HDL is generally protective.", "protein": "HDL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11242662" }, { "confidence": "high", "disease": "Hepatitis C Virus (HCV) Infection", "glycan_involvement": "VLDL glycosylation is essential for secretion and HCV particle formation.", "mechanism": "HCV interferes with VLDL assembly/secretion, altering lipid metabolism.", "protein": "VLDL", "relationship_type": "causal", "source_pmcid": "PMC11242662" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "apoB glycosylation affects lipoprotein assembly and secretion.", "mechanism": "Increase in apoB after HCV genotype 3 clearance reflects restored lipid metabolism.", "protein": "apoB", "relationship_type": "biomarker", "source_pmcid": "PMC11242662" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "apoE glycosylation influences receptor interactions.", "mechanism": "Decrease in apoE after HCV clearance; apoE modulates lipid transport.", "protein": "apoE", "relationship_type": "biomarker", "source_pmcid": "PMC11242662" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "PCSK9 is glycosylated, affecting secretion and function.", "mechanism": "High PCSK9 with low LDL-C in HIV/HCV patients (PCSK9-lipid paradox); PCSK9 regulates LDL receptor degradation.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC11242662" }, { "confidence": "high", "disease": "Hepatitis C Virus (HCV) Infection", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields from immune recognition.", "mechanism": "E2 mediates viral entry and interacts with host lipoproteins.", "protein": "Hepatitis C Virus Envelope Glycoprotein E2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11242662" }, { "confidence": "low", "disease": "Neurocognitive Impairment", "glycan_involvement": "Glycosylation modulates aggregation and toxicity.", "mechanism": "Accumulation in HIV/HCV co-infection may promote neurodegeneration.", "protein": "\u03b1-synuclein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242662" }, { "confidence": "low", "disease": "Neurocognitive Impairment", "glycan_involvement": "Glycosylation affects aggregation and clearance.", "mechanism": "Accumulation in co-infection context may contribute to neuropathogenesis.", "protein": "Amyloid \u03b2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242662" }, { "confidence": "low", "disease": "Neurocognitive Impairment", "glycan_involvement": "O-glycosylation modulates aggregation propensity.", "mechanism": "Tau accumulation linked to neurodegeneration in chronic HIV/HCV.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242662" }, { "confidence": "high", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "O-glycosylation affects K18 stability and release.", "mechanism": "Serum K18 fragments (M30/M65) released during hepatocyte injury correlate with AH severity and mortality.", "protein": "Cytokeratin 18 (K18)", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "high", "disease": "Decompensated cirrhosis (DC)", "glycan_involvement": "Glycosphingolipid structure essential for membrane integrity.", "mechanism": "Lower serum sphingomyelin levels correlate with higher fibrosis and decompensation.", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "C-type lectin domain binds glycans for pathogen recognition.", "mechanism": "Serum collectin 11 differentiates severe AH from alcoholic cirrhosis.", "protein": "Collectin 11", "protein_enriched": { "function": "Lectin that plays a role in innate immunity, apoptosis and embryogenesis (PubMed:21258343, PubMed:23954398, PubMed:25912189). Calcium-dependent lectin that binds self and non-self glycoproteins presen", "gene_name": "COLEC11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BWP8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Glycosylation modulates complement pathway activity.", "mechanism": "Lower levels in severe AH suggest enhanced complement activation.", "protein": "C1q binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Lectin pathway activation depends on glycan recognition.", "mechanism": "MASP1 levels associated with 90-day mortality in AH.", "protein": "MASP1", "protein_enriched": { "function": "Membrane-anchored forms may play a role in cellular adhesion", "gene_name": "MSLN", "glycan_count": 31, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G23505EP", "G37881RL", "G39595FH", "G45395BF", "G56784JY", "G90382BL", "G02030ZB", "G13694XX", "G22310AV", "G37399XV", "G38663NM", "G47748JZ", "G48414YA", "G51640FO", "G72667IM", "G80920RR", "G82463GQ", "G84452RH", "G91473PK", "G12793SR", "G25418HZ", "G27058EU", "G30740WO", "G33791AF", "G47518TP", "G52527GH", "G55412XP", "G57888GL", "G82830MN", "G41247ZX", "G49108TO" ], "uniprot_id": "Q13421" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "high", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "N-glycosylation critical for laminin function.", "mechanism": "Serum laminin levels diagnose AH and reflect basement membrane remodeling.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "high", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Glycosylation affects collagen IV stability and signaling.", "mechanism": "Elevated serum collagen IV indicates AH and extracellular matrix remodeling.", "protein": "Collagen type IV", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "P02462" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Glycosphingolipids in EVs mediate immune signaling.", "mechanism": "EV count and sphingolipid cargo predict AH severity and mortality.", "protein": "Extracellular Vesicle (EV) Sphingolipid Cargo", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcohol-associated hepatitis (AH)", "glycan_involvement": "Glycosylation modulates complement activity.", "mechanism": "Lower F2 levels associated with 90-day mortality in AH.", "protein": "Complement Factor F2", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "medium", "disease": "Alcoholic cirrhosis", "glycan_involvement": "Lectin domain recognizes pathogen glycans.", "mechanism": "Differentiates severe AH from alcoholic cirrhosis.", "protein": "Serum Collectin 11", "relationship_type": "biomarker", "source_pmcid": "PMC11242687" }, { "confidence": "high", "disease": "Chagas disease", "glycan_involvement": "Glycosylation required for receptor function and pathogen recognition.", "mechanism": "Controls susceptibility and parasite replication in macrophages; SLAMF1 deficiency protects against lethal Y strain infection.", "protein": "SLAMF1 (CD150)", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "CD84", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UIB8" }, "relationship_type": "causal", "source_pmcid": "PMC11242706" }, { "confidence": "high", "disease": "Chagas disease", "glycan_involvement": "Glycosylation mediates cell-cell adhesion and immune cell trafficking.", "mechanism": "Upregulated in infection; deficiency increases susceptibility and reduces T cell recruitment.", "protein": "ICAM1 (CD54)", "relationship_type": "protective", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation modulates ligand-receptor interactions.", "mechanism": "Inhibits macrophage activation and T cell proliferation; blockade reduces pathogen burden but may exacerbate immune response.", "protein": "PDL1 (CD274)", "relationship_type": "regulatory/therapeutic_target", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Downregulated in SLAMF1-deficient macrophages; involved in IL-6 and TNF-\u03b1 production.", "protein": "SLAMF5 (CD84)", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "CD84", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9UIB8" }, "relationship_type": "regulatory", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation required for antiviral function.", "mechanism": "Upregulated in SLAMF1-deficient macrophages; traps pathogens at cell surface.", "protein": "BST2 (Tetherin)", "protein_enriched": { "function": "Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR) (PubMed:7805847). Cyclic ADPR is known to serve as an endogenous second messenge", "gene_name": "BST1", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05049YU", "G06110VR", "G10486CT", "G31852PQ", "G39188ZX", "G41247ZX", "G49018RC", "G59626AS", "G62765YT", "G72747WU", "G77547TA", "G78787DI", "G90659AW", "G04657PL", "G08293MJ", "G27058EU", "G41071NU", "G42124LM", "G47644PP", "G84452RH", "G14972EH", "G79666IR", "G83646BJ", "G87661QW" ], "uniprot_id": "Q10588" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation may affect secretion and stability.", "mechanism": "Upregulated by IFN-\u03b3; promotes inflammasome activation and parasite elimination.", "protein": "GBP5", "protein_enriched": { "function": "Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (By similarity). Hydrolyzes GTP, but in contrast to ", "gene_name": "GBP5", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G08545AS", "G49108TO" ], "uniprot_id": "Q96PP8" }, "relationship_type": "protective", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation influences enzyme activity and secretion.", "mechanism": "Downregulated in infection; decreased levels may enhance cardiac disease by preventing inflammation resolution.", "protein": "MMP12", "protein_enriched": { "function": "May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic", "gene_name": "MMP12", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P39900" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242706" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Upregulated in SLAMF1-deficient macrophages; regulates innate immune response.", "protein": "IFI204", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242706" }, { "confidence": "low", "disease": "Chagas disease", "glycan_involvement": "Glycosylation may affect secretion.", "mechanism": "Upregulated in Y strain infection; restricts pathogen replication.", "protein": "RSAD2 (Viperin)", "protein_enriched": { "function": "Interferon-inducible antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon (PubMed:31812350). Catalyzes the conversion of cytidine triphosphat", "gene_name": "RSAD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXG1" }, "relationship_type": "protective", "source_pmcid": "PMC11242706" }, { "confidence": "low", "disease": "Chagas disease", "glycan_involvement": "Glycosylation required for lysosomal targeting.", "mechanism": "Downregulated in VFRA strain infection; involved in lysosomal nucleic acid degradation.", "protein": "PLD3", "protein_enriched": { "function": "5'->3' exonuclease that hydrolyzes the phosphodiester bond of single-stranded DNA (ssDNA) and RNA molecules to form nucleoside 3'-monophosphates and 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotid", "gene_name": "PLD3", "glycan_count": 40, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11870QZ", "G14669DU", "G28681TP", "G45395BF", "G47644PP", "G47950XN", "G48414YA", "G55383ZG", "G70101JE", "G72291OX", "G74724QE", "G80920RR", "G82119TF", "G85269DF", "G92050GC", "G92275SC", "G95865ZB", "G05724UK", "G06110VR", "G14260UH", "G39188ZX", "G55220VL", "G64527OM", "G83633GK", "G27058EU", "G29545VG", "G31852PQ", "G36379GD", "G43223CG", "G57776ZS", "G62765YT", "G70232NH", "G71784JC", "G79666IR", "G83460ZZ", "G26330YA", "G40574BA", "G49108TO" ], "uniprot_id": "Q8IV08" }, "relationship_type": "regulatory", "source_pmcid": "PMC11242706" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "GDF-15 is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Elevated in many cancers; promotes immune evasion, angiogenesis, metastasis, and therapy resistance via macrophage modulation and PD-L1 upregulation.", "protein": "GDF-15", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation may regulate secretion and receptor interactions.", "mechanism": "Promotes M2 macrophage polarization, fibroblast activation, and ECM accumulation; elevated in liver and lung fibrosis.", "protein": "GDF-15", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Elevated in sepsis; anti-inflammatory effects on macrophages via NF-\u03baB and PI3K/Akt inhibition, improving survival.", "protein": "GDF-15", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects stability and receptor binding.", "mechanism": "Elevated after MI; reduces immune cell recruitment, fibrosis, and remodeling; promotes M2 polarization and angiogenesis.", "protein": "GDF-15", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Obesity/Metabolic Syndrome", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Elevated in obesity; anorexigenic effect via GFRAL/RET pathway, reduces food intake and improves metabolic profile.", "protein": "GDF-15", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11242731" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation may affect circulating levels.", "mechanism": "Elevated in diabetes and complications; role in glucose tolerance and insulin resistance unclear.", "protein": "GDF-15", "relationship_type": "biomarker", "source_pmcid": "PMC11242731" }, { "confidence": "medium", "disease": "Pregnancy Complications", "glycan_involvement": "Glycosylation impacts secretion from placenta.", "mechanism": "Highly elevated in pregnancy; diagnostic relevance in preeclampsia and gestational diabetes.", "protein": "GDF-15", "relationship_type": "biomarker", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation required for hepatic secretion.", "mechanism": "Correlates with fibrosis progression in NAFLD and alcoholic liver disease; modulates Kupffer cell apoptosis and immune infiltration.", "protein": "GDF-15", "relationship_type": "biomarker/causal/protective", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Lung Fibrosis", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated in pulmonary fibrosis; produced by macrophages and epithelial cells, affects macrophage activation and alveolarization.", "protein": "GDF-15", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "YKL-40 is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "Produced by M2 macrophages; induces GDF-15 in tumor cells, promoting invasion and PD-L1 upregulation for immune evasion.", "protein": "YKL-40", "relationship_type": "causal", "source_pmcid": "PMC11242731" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "Mediates platelet aggregation during thrombosis after plaque rupture.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates multimer formation and activity.", "mechanism": "Facilitates platelet adhesion to exposed collagen after endothelial damage.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Familial hypercholesterolaemia", "glycan_involvement": "N-glycosylation required for proper folding and cell surface expression.", "mechanism": "Mutations impair LDL uptake, leading to high LDL-C and early atherosclerosis.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "causal", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Familial hypercholesterolaemia", "glycan_involvement": "Glycosylation affects LDL particle stability and receptor interaction.", "mechanism": "Defective APOB impairs LDLR binding, increasing LDL-C and atherosclerosis risk.", "protein": "Apolipoprotein B (APOB)", "relationship_type": "causal", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Familial hypercholesterolaemia", "glycan_involvement": "Glycosylation influences secretion and activity.", "mechanism": "Gain-of-function mutations increase LDLR degradation, raising LDL-C.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Elevated CRP reflects systemic inflammation and predicts cardiovascular risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242737" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects secretion and inhibitory activity.", "mechanism": "Elevated PAI-1 promotes thrombosis and vascular complications in diabetes.", "protein": "PAI-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242737" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates receptor binding and activity.", "mechanism": "Promotes inflammation and plaque instability.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation required for cell surface expression and activity.", "mechanism": "Initiates coagulation cascade after plaque rupture, leading to thrombosis.", "protein": "Tissue factor", "relationship_type": "causal", "source_pmcid": "PMC11242737" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may affect stability and detection.", "mechanism": "Released from damaged cardiomyocytes; diagnostic for MI.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC11242737" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "C4 is a glycoprotein; glycosylation may affect its fragmentation and biomarker potential.", "mechanism": "Serum fragment P-2378 (from C4) positively correlates with hematometabolic index (HMI), reflecting increased cardiometabolic risk.", "protein": "Complement component 4 (C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "medium", "disease": "Lower extremity artery disease (LEAD)", "glycan_involvement": "Glycosylation may influence C4 fragment generation and disease association.", "mechanism": "Serum fragment P-2378 associates with degree of leg ischemia in LEAD patients.", "protein": "Complement component 4 (C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "medium", "disease": "Hypertensive disorders of pregnancy (HDP)", "glycan_involvement": "Glycosylation status may affect peptide detection and disease linkage.", "mechanism": "P-2378 identified as HDP-associated peptide biomarker.", "protein": "Complement component 4 (C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "ITIH4 is glycosylated; glycan structure may modulate fragmentation and biomarker utility.", "mechanism": "Serum fragment P-3156 (from ITIH4) inversely correlates with lipid accumulation product (LAP), indicating lower cardiometabolic risk.", "protein": "Inter-\u03b1-trypsin inhibitor heavy chain H4 (ITIH4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "medium", "disease": "Hypertensive disorders of pregnancy (HDP)", "glycan_involvement": "Glycosylation may affect peptide stability and disease association.", "mechanism": "P-3156 identified as HDP-associated peptide biomarker.", "protein": "Inter-\u03b1-trypsin inhibitor heavy chain H4 (ITIH4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "low", "disease": "Hypertensive disorders of pregnancy (HDP)", "glycan_involvement": "Fibrinogen-\u03b1 is glycosylated; glycan status may influence peptide generation.", "mechanism": "P-2091 fragment identified as HDP-associated peptide biomarker.", "protein": "Fibrinogen-\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "low", "disease": "Hypertensive disorders of pregnancy (HDP)", "glycan_involvement": "Kininogen glycosylation may affect peptide fragmentation.", "mechanism": "Fragments P-2081, P-2127, P-2209 identified as HDP-associated peptide biomarkers.", "protein": "Kininogen", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "low", "disease": "Hypertensive disorders of pregnancy (HDP)", "glycan_involvement": "Fetuin-A is highly glycosylated; glycan modifications may impact biomarker properties.", "mechanism": "P-2858 fragment identified as HDP-associated peptide biomarker.", "protein": "\u03b1-2-HS-glycoprotein (Fetuin-A)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation may modulate C4 fragmentation and biomarker function.", "mechanism": "P-2378 fragment correlates with HMI, a marker for metabolic syndrome risk.", "protein": "Complement component 4 (C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation may influence ITIH4 fragment generation.", "mechanism": "P-3156 fragment inversely correlates with LAP, a marker for metabolic syndrome risk.", "protein": "Inter-\u03b1-trypsin inhibitor heavy chain H4 (ITIH4)", "relationship_type": "biomarker", "source_pmcid": "PMC11242742" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I drive thrombosis and vascular inflammation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242764" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Anti-\u03b22GPI antibodies increase risk of arterial thrombosis leading to stroke.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "APS", "glycan_involvement": "Glycosylation may affect epitope exposure.", "mechanism": "IgG anti-prothrombin antibodies associated with CNS manifestations in APS.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "APS", "glycan_involvement": "Glycosylation may influence membrane binding.", "mechanism": "IgG anti-annexin V antibodies linked to CNS involvement in APS.", "protein": "Annexin V", "relationship_type": "biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "Cognitive Impairment/Dementia", "glycan_involvement": "Glycosylation impacts antibody affinity.", "mechanism": "High titers of anti-\u03b22GPI antibodies correlate with cognitive dysfunction.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "Small Vessel Disease (SVD)", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "Anti-\u03b22GPI antibodies promote microvascular thrombosis and SVD lesions.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC11242764" }, { "confidence": "low", "disease": "Moyamoya Arteriopathy", "glycan_involvement": "Glycosylation may affect vascular cell interactions.", "mechanism": "aPLs including anti-\u03b22GPI may contribute to vascular stenosis and collateral formation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "Proliferative Vasculopathy (PV-aPL)", "glycan_involvement": "Glycosylation influences cytokine release and cell activation.", "mechanism": "aPLs stimulate endothelial proliferation, leading to nonthrombotic vascular stenosis.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC11242764" }, { "confidence": "medium", "disease": "Cerebral Venous Thrombosis (CVT)", "glycan_involvement": "Glycosylation may affect antibody binding.", "mechanism": "Anti-cardiolipin antibodies associated with increased CVT risk.", "protein": "Cardiolipin-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "low", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may modulate immune cross-reactivity.", "mechanism": "Elevated anti-\u03b22GPI antibodies observed in MS, but causal link unclear.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11242764" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Autoantigen targeted by immune response, leading to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC11242768" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation required for stability and bioactivity.", "mechanism": "IFN\u03b2 suppresses neuroinflammation and immune cell infiltration.", "protein": "Interferon Beta (IFN\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242768" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates signaling.", "mechanism": "Marker of infiltrating leukocytes in CNS during neuroinflammation.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242768" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation affects cell adhesion and migration.", "mechanism": "Identifies infiltrating myeloid cells (monocytes, granulocytes) in CNS.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242768" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation modulates peptide binding and T cell activation.", "mechanism": "Antigen presentation to T cells drives autoimmune response.", "protein": "MHC II", "relationship_type": "causal", "source_pmcid": "PMC11242768" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation influences immune cell trafficking.", "mechanism": "Identifies granulocytes and monocytes infiltrating CNS.", "protein": "GR-1 (Ly6G/Ly6C)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11242768" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation modulates receptor function and cell-cell interactions.", "mechanism": "NK cell infiltration and IFN\u03b3 production contribute to pathology.", "protein": "NK1.1 (Klrb1c)", "protein_enriched": { "function": "Possible taste receptor", "gene_name": "Or13a27", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1T9" }, "relationship_type": "causal", "source_pmcid": "PMC11242768" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation affects TCR stability and antigen recognition.", "mechanism": "T cell receptor mediates autoimmune attack on CNS antigens.", "protein": "TCR\u03b2", "protein_enriched": { "function": "", "gene_name": "Ighg2b", "glycan_count": 6, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G07075ND", "G15488CF", "G39397SW", "G64161CC", "G78224CS", "G49108TO" ], "uniprot_id": "P01867" }, "relationship_type": "causal", "source_pmcid": "PMC11242768" }, { "confidence": "low", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may regulate enzyme activity.", "mechanism": "Arg1 expression reflects anti-inflammatory macrophage activation.", "protein": "Arginase 1 (Arg1)", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592)", "gene_name": "Rpl13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47963" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242768" }, { "confidence": "low", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation influences filament assembly and cell signaling.", "mechanism": "Astrocyte activation and gliosis during neuroinflammation.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242768" }, { "confidence": "high", "disease": "Bone fracture", "glycan_involvement": "N-linked glycosylation (SIBLING family)", "mechanism": "Suppresses over-mineralization, modulates osteoclast function, reducing fracture risk", "protein": "Osteopontin", "relationship_type": "protective", "source_pmcid": "PMC11242793" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-linked glycosylation modulates function", "mechanism": "Increases cell migration and inflammation, contributing to atherosclerotic processes", "protein": "Osteopontin", "relationship_type": "causal", "source_pmcid": "PMC11242793" }, { "confidence": "medium", "disease": "Cancer (bone metastasis)", "glycan_involvement": "N-linked glycosylation modulates cell adhesion/migration", "mechanism": "Promotes cell migration and tumor invasiveness", "protein": "Osteopontin", "relationship_type": "causal", "source_pmcid": "PMC11242793" }, { "confidence": "medium", "disease": "Nephrolithiasis", "glycan_involvement": "N-linked glycosylation", "mechanism": "Prevents kidney stone formation", "protein": "Osteopontin", "relationship_type": "protective", "source_pmcid": "PMC11242793" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for secretion and stability", "mechanism": "High serum levels associated with obesity and metabolic syndrome", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242793" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates bioactivity", "mechanism": "Elevated in insulin resistance and metabolic disorders", "protein": "Lipocalin 2", "protein_enriched": { "function": "Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association wit", "gene_name": "LCN2", "glycan_count": 24, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G05724UK", "G06356OH", "G08918WF", "G11314AS", "G27058EU", "G36379GD", "G37868ZX", "G43223CG", "G45495MK", "G45504EY", "G57317CE", "G59626AS", "G71146HJ", "G74724QE", "G75983OB", "G76295SF", "G79666IR", "G80075MS", "G80920RR", "G84452RH", "G85269DF", "G86880BF", "G92275SC" ], "uniprot_id": "P80188" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242793" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects secretion and function", "mechanism": "Inhibits Wnt signaling, reducing bone formation; overexpression leads to osteoporosis", "protein": "Sclerostin", "protein_enriched": { "function": "Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation", "gene_name": "SOST", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9BQB4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11242793" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation modulates stability", "mechanism": "Serum DKK1 levels increased in multiple myeloma, inhibits Wnt signaling", "protein": "DKK1", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:220", "gene_name": "DKK1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "O94907" }, "relationship_type": "biomarker", "source_pmcid": "PMC11242793" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "O-glycosylation required for secretion", "mechanism": "Elevated in mineralization disorders and CKD, regulates phosphate homeostasis", "protein": "FGF23", "relationship_type": "biomarker", "source_pmcid": "PMC11242793" }, { "confidence": "medium", "disease": "Cancer (bone metastasis)", "glycan_involvement": "N-linked glycosylation (SIBLING family)", "mechanism": "Associated with bone metastatic potential in cancers", "protein": "Bone sialoprotein (BSP)", "relationship_type": "causal", "source_pmcid": "PMC11242793" }, { "confidence": "high", "disease": "Pan-tumor (multiple cancers)", "glycan_involvement": "Glycosylation modulates Tenascin-C's ECM interactions and EV packaging.", "mechanism": "Tenascin-C carried by EVs enables sensitive pan-cancer liquid biopsy.", "protein": "Tenascin-C", "relationship_type": "biomarker", "source_pmcid": "PMC11245638" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects ECM1-integrin binding and EV sorting.", "mechanism": "ECM1 in sEVs interacts with integrin beta-2, promoting breast cancer growth and metastasis, especially under obesity.", "protein": "ECM1", "protein_enriched": { "function": "Involved in endochondral bone formation as negative regulator of bone mineralization. Stimulates the proliferation of endothelial cells and promotes angiogenesis. Inhibits MMP9 proteolytic activity", "gene_name": "ECM1", "glycan_count": 48, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G06356OH", "G34617SM", "G41882MT", "G47748JZ", "G64394MX", "G93656SY", "G03382KH", "G04657PL", "G07755XJ", "G11629QQ", "G14972EH", "G17208MA", "G27058EU", "G29880MM", "G31852PQ", "G34989PA", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G59626AS", "G62765YT", "G70232NH", "G72667IM", "G74724QE", "G76295SF", "G77669RF", "G80920RR", "G81263BG", "G83460ZZ", "G84452RH", "G90382BL", "G90659AW", "G22310AV", "G39188ZX", "G43089EG", "G52527GH", "G82830MN", "G23453IV", "G55412XP", "G57776ZS", "G61256FT", "G77380JK", "G81006GJ", "G49108TO" ], "uniprot_id": "Q16610" }, "relationship_type": "causal", "source_pmcid": "PMC11245638" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation regulates integrin activation and ECM1 binding.", "mechanism": "Integrin beta-2 partners with ECM1 in sEVs to enhance tumor progression.", "protein": "Integrin beta-2", "relationship_type": "causal", "source_pmcid": "PMC11245638" }, { "confidence": "medium", "disease": "Intracranial aneurysm", "glycan_involvement": "Glycosylation modulates PECAM1's adhesive properties and EV incorporation.", "mechanism": "PECAM1+ EVs in plasma serve as biomarkers for unruptured intracranial aneurysm.", "protein": "PECAM1 (CD31)", "relationship_type": "biomarker", "source_pmcid": "PMC11245638" }, { "confidence": "medium", "disease": "Intracranial aneurysm", "glycan_involvement": "N-glycosylation influences integrin clustering and EV targeting.", "mechanism": "ITGB1+ EVs are elevated in plasma of patients with unruptured intracranial aneurysm.", "protein": "ITGB1 (Integrin beta-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11245638" }, { "confidence": "high", "disease": "Oral cancer", "glycan_involvement": "PD-L1 glycosylation affects immune evasion and EV stability.", "mechanism": "PD-L1+ EVs detected by sEV-PREDICT platform for immunotherapy monitoring.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11245638" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "C1q glycosylation modulates complement activation and EV loading.", "mechanism": "EV-transported C1q promotes neuronal amyloid-beta production.", "protein": "Complement C1q", "relationship_type": "causal", "source_pmcid": "PMC11245638" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation affects GCC2's Golgi localization and EV release.", "mechanism": "High sEV-GCC2 in pulmonary veins predicts prognosis after lung adenocarcinoma surgery.", "protein": "GCC2", "relationship_type": "biomarker", "source_pmcid": "PMC11245638" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "FGF21 glycosylation impacts receptor binding and EV display.", "mechanism": "Engineered EVs with surface FGF21 treat NASH by modulating metabolism.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11245638" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation regulates CD9's membrane localization and EV formation.", "mechanism": "CD9-mEmerald reporter mice used to detect EVs in hepatotoxicity and lung injury.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC11245638" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Dense N-glycosylation shields epitopes, modulates immune evasion.", "mechanism": "gp120 mediates viral entry and is a major target of neutralizing antibodies; highly glycosylated, shields virus from immune recognition.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC11264349" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation patterns affect immunogenicity and antibody recognition.", "mechanism": "gp140 is used as an immunogen in vaccines to elicit broadly neutralizing antibodies.", "protein": "HIV-1 gp140", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "Mother-to-child HIV transmission (breastfeeding)", "glycan_involvement": "Glycosylation of gp41 influences antibody binding and Fc-mediated functions.", "mechanism": "Higher IgG and Fc\u03b3R binding to gp41 in breastmilk associated with increased HIV transmission risk.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "Mother-to-child HIV transmission (breastfeeding)", "glycan_involvement": "Fc glycosylation modulates receptor binding and effector function.", "mechanism": "Elevated IgG and Fc\u03b3R2A/B binding in transmitting mothers' milk; Fc-mediated effector functions linked to transmission.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "Impaired vaccine response in HIV-exposed uninfected infants", "glycan_involvement": "Glycosylation of TT influences immunogenicity and antibody response.", "mechanism": "Lower anti-TT IgG titres in HIV-exposed uninfected infants indicate impaired vaccine response.", "protein": "Tetanus toxoid", "protein_enriched": { "function": "Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can mov", "gene_name": "tetX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04958" }, "relationship_type": "biomarker", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "HIV persistence/reservoirs", "glycan_involvement": "Tat is not a classical glycoprotein but interacts with glycosylated cell surface receptors.", "mechanism": "Tat-based vaccine induces anti-Tat antibodies, reduces viral reservoirs and improves immune function.", "protein": "HIV-1 Tat", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "Mother-to-child HIV transmission (breastfeeding)", "glycan_involvement": "Fc\u03b3R glycosylation affects IgG binding and downstream signaling.", "mechanism": "Higher Fc\u03b3R2A binding to gp41/gp140 in transmitting mothers' milk associated with increased transmission.", "protein": "Fc\u03b3R2A", "relationship_type": "biomarker", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "IgG3 glycosylation modulates Fc effector functions.", "mechanism": "High IgG3 responses to V1V2 region correlate with vaccine-induced protection.", "protein": "IgG3", "relationship_type": "protective", "source_pmcid": "PMC11264349" }, { "confidence": "low", "disease": "HIV-associated vaccine failure", "glycan_involvement": "TTB is a glycoprotein scaffold; glycosylation may affect mucosal immune interactions.", "mechanism": "Oral nanoparticle delivery of TTB (without V2 peptide) shifts mucosal immunity to non-protective state, reducing vaccine efficacy.", "protein": "Typhoid Toxin B subunit (TTB)", "relationship_type": "causal", "source_pmcid": "PMC11264349" }, { "confidence": "medium", "disease": "HIV-associated gut barrier dysfunction", "glycan_involvement": "Glycosylation modulates tissue tropism and immune evasion.", "mechanism": "gp120 targets gut-resident CD4+ T cells, contributing to depletion and epithelial dysfunction.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC11264349" }, { "confidence": "high", "disease": "Spring viremia of carp (SVC)", "glycan_involvement": "G protein is a viral glycoprotein mediating host cell attachment and entry.", "mechanism": "SVCV G protein is essential for viral entry and infection, causing SVC in fish.", "protein": "Glycoprotein (G protein) of SVCV", "relationship_type": "causal", "source_pmcid": "PMC11267047" }, { "confidence": "high", "disease": "SVCV infection", "glycan_involvement": "Glycosylation of G protein is important for immunogenicity and function.", "mechanism": "SVCV G protein is targeted in DNA vaccine development to induce protective immunity.", "protein": "Glycoprotein (G protein) of SVCV", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11267047" }, { "confidence": "high", "disease": "SVCV infection", "glycan_involvement": "No direct glycosylation involvement described for STING in this context.", "mechanism": "STING activation induces IFN response, enhancing antiviral defense against SVCV.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "protective", "source_pmcid": "PMC11267047" }, { "confidence": "high", "disease": "SVCV infection", "glycan_involvement": "No direct glycosylation involvement described for STING in this context.", "mechanism": "STING stability and expression are promoted by Mn2+, enhancing antiviral immunity.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11267047" }, { "confidence": "medium", "disease": "Spring viremia of carp (SVC)", "glycan_involvement": "Glycosylation status may affect detection and immune recognition.", "mechanism": "G protein gene is used as a marker in diagnostic and vaccine studies.", "protein": "Glycoprotein (G protein) of SVCV", "relationship_type": "biomarker", "source_pmcid": "PMC11267047" }, { "confidence": "high", "disease": "Bacterial infection (Edwardsiella piscicida)", "glycan_involvement": "N-glycosylation sites may affect protein stability and function in pathogen binding.", "mechanism": "Ss HPX expression is upregulated in intestine after infection, binds bacteria, and inhibits bacterial proliferation.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "protective", "source_pmcid": "PMC11298604" }, { "confidence": "high", "disease": "Inflammation (acute-phase/inflammatory response)", "glycan_involvement": "N-glycosylation may modulate cytokine interaction and immune regulation.", "mechanism": "Ss HPX regulates pro- and anti-inflammatory cytokine expression, reducing excessive inflammation during infection.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "regulator/protective", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Bacterial infection (Edwardsiella piscicida)", "glycan_involvement": "Glycosylation may be required for full bacteriostatic activity.", "mechanism": "Recombinant Ss HPX reduces bacterial proliferation and inflammatory cytokine expression in vitro.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Inflammation (acute-phase/inflammatory response)", "glycan_involvement": "N-glycosylation may affect secretion and stability as a biomarker.", "mechanism": "Ss HPX is strongly upregulated in intestine during infection, indicating acute-phase response.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "biomarker", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Bacterial infection (Edwardsiella piscicida)", "glycan_involvement": "Glycosylation may influence ligand binding affinity.", "mechanism": "Ss HPX directly binds microbial ligands (LPS, LTA, PGN), contributing to pathogen recognition and clearance.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "causal", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Inflammation (acute-phase/inflammatory response)", "glycan_involvement": "N-glycosylation may regulate anti-inflammatory function.", "mechanism": "Ss HPX inhibits both pro- and anti-inflammatory cytokine overexpression, preventing tissue damage.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "protective", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Inflammation (acute-phase/inflammatory response)", "glycan_involvement": "N-glycosylation may affect cytokine modulation.", "mechanism": "Ss HPX downregulates pro-inflammatory cytokines (il-1\u03b2, il-8, cxcl8, il-17c) and upregulates anti-inflammatory cytokine (il-10) during infection.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "regulator", "source_pmcid": "PMC11298604" }, { "confidence": "medium", "disease": "Bacterial infection (Edwardsiella piscicida)", "glycan_involvement": "N-glycosylation may enhance bacteriostatic effect.", "mechanism": "Ss HPX acts as a bacteriostatic agent, reducing pathogen load in vitro in a dose-dependent manner.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "protective", "source_pmcid": "PMC11298604" }, { "confidence": "low", "disease": "Inflammation (acute-phase/inflammatory response)", "glycan_involvement": "N-glycosylation may influence protein-protein interactions.", "mechanism": "Ss HPX modulates expression of plasminogen (plg) and MAP3K7, impacting inflammatory signaling.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "regulator", "source_pmcid": "PMC11298604" }, { "confidence": "low", "disease": "Bacterial infection (Edwardsiella piscicida)", "glycan_involvement": "N-glycosylation may be important for secretion and stability.", "mechanism": "Ss HPX is rapidly synthesized and secreted in response to infection, contributing to early host defense.", "protein": "Hemopexin (Ss HPX)", "relationship_type": "protective", "source_pmcid": "PMC11298604" }, { "confidence": "high", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycosylation is essential for proper folding and function of the IIb/IIIa complex, which mediates platelet aggregation.", "mechanism": "Glycoprotein IIb/IIIa inhibitors are used as antiplatelet agents to prevent platelet aggregation and thrombosis during acute myocardial infarction.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11307803" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a CNS glycoprotein; glycosylation may affect antigenicity.", "mechanism": "MOG peptide immunization induces EAE, modeling MS pathology.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "ZO-1 is glycosylated, which may affect tight junction stability.", "mechanism": "ZO-1 levels decrease in EAE/MS, indicating BBB breakdown.", "protein": "ZO-1 (Tight junction protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Claudin-5 is glycosylated; glycosylation may regulate barrier function.", "mechanism": "Claudin-5 decreases in EAE/MS, reflecting BBB dysfunction.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CCL2 is glycosylated, influencing secretion and function.", "mechanism": "CCL2 is upregulated in EAE/MS, promoting myeloid cell infiltration.", "protein": "CCL2 (MCP-1)", "relationship_type": "causal", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CXCL1 glycosylation may modulate chemokine activity.", "mechanism": "CXCL1 is increased in EAE/MS, attracting neutrophils to CNS.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "causal", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CCL4 glycosylation may affect chemokine gradient formation.", "mechanism": "CCL4 is upregulated in EAE/MS, facilitating immune cell recruitment.", "protein": "CCL4", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of ", "gene_name": "CCL4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13236" }, "relationship_type": "causal", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may stabilize ZO-1 at tight junctions.", "mechanism": "ZO-1 loss marks BBB disruption in EAE.", "protein": "ZO-1 (Tight junction protein 1)", "relationship_type": "biomarker", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation may regulate Claudin-5 localization/function.", "mechanism": "Claudin-5 reduction signals BBB compromise in EAE.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects CCL2 secretion and receptor binding.", "mechanism": "CCL2 drives leukocyte infiltration during neuroinflammation.", "protein": "CCL2 (MCP-1)", "relationship_type": "causal", "source_pmcid": "PMC11338344" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may modulate Claudin-5's barrier properties.", "mechanism": "Claudin-5 loss is associated with increased BBB permeability in neuroinflammation.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC11338344" }, { "confidence": "high", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Direct recognition of mannose-rich glycans on pathogens.", "mechanism": "Millectin binds pathogen-associated glycans, activating complement C3-Am and promoting phagocytosis.", "protein": "Millectin", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "high", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Carbohydrate recognition domain binds galactose and derivatives.", "mechanism": "SpEchinoidin binds galactose residues on pathogens, facilitating agglutination and immune clearance.", "protein": "SpEchinoidin", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "high", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Activation via lectin pathway recognizing pathogen glycans.", "mechanism": "C3-Am is activated by lectin binding, leading to opsonization and lysis of pathogens.", "protein": "Complement C3-Am", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Direct glycan recognition on microbial surfaces.", "mechanism": "SRCR domains recognize and bind microbial glycans, mediating phagocytosis.", "protein": "SRCR domains", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Symbiont dysbiosis", "glycan_involvement": "Binds specific glycans on symbiont surfaces.", "mechanism": "Techylectin mediates recognition and selection of symbiotic bacteria via glycan binding.", "protein": "Techylectin", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Lectin pathway activation via pathogen glycans.", "mechanism": "MASP, activated by mannose-binding lectin, triggers complement cascade against pathogens.", "protein": "MASP", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Binds to glycosylated pathogen surfaces.", "mechanism": "C1q recognizes pathogen-associated glycans, initiating complement activation.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Opportunistic bacterial infection", "glycan_involvement": "Direct glycan recognition.", "mechanism": "Ficolin binds N-acetylglucosamine on pathogens, activating complement.", "protein": "Ficolin", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Fungal infection", "glycan_involvement": "Lectin-glycan interaction.", "mechanism": "Agglutinins bind to fungal cell wall glycans, causing aggregation and immune clearance.", "protein": "Agglutinins", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "medium", "disease": "Symbiont dysbiosis", "glycan_involvement": "Mediates cell-cell and cell-microbe adhesion via glycan binding.", "mechanism": "TSR domain proteins mediate symbiont selection via glycan-dependent adhesion.", "protein": "Thrombospondin-type-1 repeat (TSR) domain proteins", "relationship_type": "protective", "source_pmcid": "PMC11359984" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "oxMIF is a conformational isoform of the glycoprotein MIF; glycosylation may affect its cell surface binding.", "mechanism": "oxMIF accumulates in tumor tissue and is targeted by bispecific antibodies for radioimmunotherapy, leading to tumor regression.", "protein": "oxMIF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11372362" }, { "confidence": "high", "disease": "Pancreatic Ductal Adenocarcinoma (PDAC)", "glycan_involvement": "oxMIF derives from glycoprotein MIF; glycosylation may influence its tumor-specific conformation.", "mechanism": "oxMIF is present in PDAC tissue and can be targeted by ON105 for effective tumor growth inhibition.", "protein": "oxMIF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "oxMIF is a glycoprotein isoform; glycosylation may affect detection.", "mechanism": "oxMIF is detected in ovarian cancer tissue, indicating disease presence.", "protein": "oxMIF", "relationship_type": "biomarker", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Squamous Cell Carcinoma of the Lung", "glycan_involvement": "oxMIF is a glycoprotein isoform; glycosylation may affect detection.", "mechanism": "oxMIF is present in tumor tissue, serving as a disease marker.", "protein": "oxMIF", "relationship_type": "biomarker", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Liver Metastases", "glycan_involvement": "oxMIF is a glycoprotein isoform; glycosylation may affect detection.", "mechanism": "oxMIF is detected in metastatic liver tissue from colorectal cancer.", "protein": "oxMIF", "relationship_type": "biomarker", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Chronic Inflammatory Diseases", "glycan_involvement": "oxMIF is a glycoprotein isoform; glycosylation may modulate immune recognition.", "mechanism": "oxMIF is generated in proinflammatory environments and contributes to disease pathogenesis.", "protein": "oxMIF", "relationship_type": "causal", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "MIF is a glycoprotein; glycosylation may affect secretion and function.", "mechanism": "MIF acts as a proinflammatory and protumorigenic cytokine implicated in cancer pathogenesis.", "protein": "MIF", "relationship_type": "causal", "source_pmcid": "PMC11372362" }, { "confidence": "high", "disease": "Solid Tumors", "glycan_involvement": "CEA is a heavily glycosylated cell surface protein; glycosylation is critical for its function and antibody recognition.", "mechanism": "CEA is targeted by bispecific antibodies in pretargeted radioimmunotherapy for tumor imaging and therapy.", "protein": "CEA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11372362" }, { "confidence": "low", "disease": "Non-Hodgkin Lymphoma", "glycan_involvement": "oxMIF is a glycoprotein isoform.", "mechanism": "oxMIF is not directly mentioned as a target in NHL, but MIF/oxMIF may be relevant in the tumor microenvironment.", "protein": "oxMIF", "relationship_type": "biomarker", "source_pmcid": "PMC11372362" }, { "confidence": "medium", "disease": "Metastatic Cancer (general)", "glycan_involvement": "oxMIF is a glycoprotein isoform.", "mechanism": "oxMIF is detected in primary and metastatic tumor tissues, indicating disease progression.", "protein": "oxMIF", "relationship_type": "biomarker", "source_pmcid": "PMC11372362" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation affects PSMA stability and cell surface expression.", "mechanism": "PSMA is overexpressed in prostate cancer cells and targeted for imaging and therapy.", "protein": "PSMA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "high", "disease": "Neuroendocrine tumors (NETs)", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "SSTr is overexpressed in NETs and targeted by radiolabeled peptides for imaging.", "protein": "SSTr", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation influences HER2 dimerization and antibody recognition.", "mechanism": "HER2 overexpression is used for diagnosis and targeted therapy in breast cancer.", "protein": "HER2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "medium", "disease": "Various cancers", "glycan_involvement": "Glycosylation may regulate TIGIT stability and immune interactions.", "mechanism": "TIGIT is an immune checkpoint associated with poor prognosis in cancer.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation affects CXCR4 trafficking and ligand binding.", "mechanism": "CXCR4 is overexpressed in multiple myeloma and targeted for imaging.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation is critical for receptor function and ligand recognition.", "mechanism": "Folate receptor is overexpressed in ovarian cancer and used for targeted drug delivery.", "protein": "Folate receptor", "protein_enriched": { "function": "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, P", "gene_name": "FOLR1", "glycan_count": 68, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G23294PN", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G59536GA", "G60177UT", "G62765YT", "G65184UU", "G66088HZ", "G66163OV", "G68490OW", "G70101JE", "G71051TA", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90382BL", "G92135MA", "G95133RI", "G98611JV", "G99668VU", "G92062TF", "G04657PL", "G05049YU", "G07755XJ", "G10819WX", "G11870QZ", "G13131HA", "G15169WU", "G15664MX", "G20210JR", "G23719VF", "G23984SE", "G31852PQ", "G36379GD", "G42124LM", "G45504EY", "G62894KT", "G70619PT", "G77547TA", "G84225JN", "G90659AW", "G95177YH", "G49108TO" ], "uniprot_id": "P15328" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "high", "disease": "Glioma", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "IDH1-R132H mutation is a diagnostic biomarker for glioma.", "protein": "IDH1 (mutant)", "relationship_type": "biomarker", "source_pmcid": "PMC11411019" }, { "confidence": "medium", "disease": "Tumorigenesis (general)", "glycan_involvement": "Glycosylation may affect enzyme stability and localization.", "mechanism": "COX-2 is overexpressed in tumors and targeted for imaging and therapy.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "medium", "disease": "Tumorigenesis (general)", "glycan_involvement": "Glycosylation may affect enzyme function.", "mechanism": "5-LO is overexpressed in tumors and targeted for imaging and therapy.", "protein": "5-LO", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation of HER2 affects antibody binding.", "mechanism": "HER2 targeted by trastuzumab-functionalized nanoparticles for cytotoxic delivery in ovarian cancer.", "protein": "HER2 (trastuzumab-targeted)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11411019" }, { "confidence": "high", "disease": "Tumor", "glycan_involvement": "Glycosylation patterns influence biomarker properties", "mechanism": "Abnormal expression in tumor tissues; used in diagnosis and therapy", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11414713" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "O-glycans form mucus barrier; loss impairs protection", "mechanism": "Decreased expression correlates with disease severity", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC11414713" }, { "confidence": "high", "disease": "Ventilator-associated pneumonia", "glycan_involvement": "O-glycosylation forms gel-like mucus trapping pathogens", "mechanism": "High expression and excessive secretion contribute to disease progression", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "causal", "source_pmcid": "PMC11414713" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Glycosylation may affect cell signaling and adhesion", "mechanism": "Abnormally high expression associated with cancer development", "protein": "MUC15", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11414713" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may modulate anti-metastatic function", "mechanism": "Inhibits metastasis of gastric cancer cells", "protein": "MUC17", "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "high", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "O-glycans form mucus barrier against pathogens", "mechanism": "High expression in mucosal tissues; regulated after infection", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "high", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "O-glycosylation forms gel-like barrier", "mechanism": "Upregulated in skin/intestine after infection; contributes to mucosal defense", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "medium", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "O-glycans contribute to mucus viscosity and pathogen trapping", "mechanism": "Regulated in mucosal tissues after infection; involved in defense", "protein": "MUC5B", "protein_enriched": { "function": "Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus", "gene_name": "MUC5B", "glycan_count": 47, "glycosylation_sites_count": 38, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G62765YT", "G80920RR", "G84452RH", "G48414YA", "G66760KM", "G57321FI", "G64527OM", "G39188ZX", "G31852PQ", "G70822IO", "G75983OB", "G05724UK", "G06110VR", "G10773YW", "G29880MM", "G46687AB", "G82119TF", "G02030ZB", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G40142JY", "G42665KV", "G49582PC", "G58272ZE", "G63110FE", "G63628AV", "G63760GT", "G64973KT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G78315FS", "G79243QP", "G81006GJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q9HC84" }, "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "medium", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "Glycosylation may modulate immune interactions", "mechanism": "Expression regulated in mucosal tissues after infection", "protein": "MUC15", "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "medium", "disease": "Aeromonas hydrophila infection", "glycan_involvement": "O-glycans contribute to mucus structure", "mechanism": "Downregulated in mucosal tissues after infection; role in defense", "protein": "MUC19", "relationship_type": "protective", "source_pmcid": "PMC11414713" }, { "confidence": "high", "disease": "Mitochondrial disease with cardiac involvement", "glycan_involvement": "Not specified", "mechanism": "ACAD9 mutations cause mitochondrial dysfunction leading to cardiac involvement", "protein": "ACAD9", "protein_enriched": { "function": "Belongs to an adhesion system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). May connect the nectin-afadin and E-cadherin-caten", "gene_name": "SSX2IP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2D8" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Autosomal Dominant Optic Atrophy (ADOA)", "glycan_involvement": "Not specified", "mechanism": "OPA1 mutations disrupt mitochondrial fusion, causing RGC degeneration", "protein": "OPA1", "protein_enriched": { "function": "Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain f", "gene_name": "OPA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60313" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "MELAS", "glycan_involvement": "Not applicable", "mechanism": "m.3243A>G variant in MT-TL1 impairs mitochondrial protein synthesis", "protein": "MT-TL1", "protein_enriched": { "function": "DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation. Predominantly acts as a RNA-bin", "gene_name": "YBX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P67808" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Leigh syndrome", "glycan_involvement": "Not specified", "mechanism": "Pathogenic variants in MT-ATP6 disrupt ATP synthase, causing energy failure", "protein": "MT-ATP6", "protein_enriched": { "function": "Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generate", "gene_name": "MT-ATP6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00846" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Leigh syndrome", "glycan_involvement": "Not specified", "mechanism": "NDUFS4 mutations impair complex I assembly, leading to neurodegeneration", "protein": "NDUFS4", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "NDUFS4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43181" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Leigh syndrome", "glycan_involvement": "Not specified", "mechanism": "NDUFAF6 variants disrupt complex I assembly, causing LS", "protein": "NDUFAF6", "protein_enriched": { "function": "Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, PubMed:25678554). Involved in mid-late stages of complex I assembly (PubMed:2", "gene_name": "FOXRED1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96CU9" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Sodium-dependent multivitamin transporter deficiency (SMVTD)", "glycan_involvement": "Glycosylation likely affects transporter stability and trafficking", "mechanism": "SLC5A6 mutations impair biotin/pantothenate/lipoic acid transport, causing metabolic and neurodevelopmental defects", "protein": "SLC5A6", "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Thymidine kinase 2 deficiency (TK2d)", "glycan_involvement": "Not specified", "mechanism": "TK2 mutations impair mitochondrial DNA maintenance, causing myopathy", "protein": "Thymidine kinase 2", "protein_enriched": { "function": "Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix (PubMed:11687801, PubMed:9989599). In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtD", "gene_name": "TK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00142" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "MEPAN syndrome", "glycan_involvement": "Not specified", "mechanism": "MECR loss-of-function disrupts mitochondrial fatty acid synthesis, leading to neurodegeneration", "protein": "MECR", "protein_enriched": { "function": "Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II). Fatty acid chain elongation in mitochondria uses acyl carrier ", "gene_name": "MECR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BV79" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "medium", "disease": "MEPAN syndrome", "glycan_involvement": "Not specified", "mechanism": "AASDHPPT is required for mtACP activation; loss impairs mitochondrial fatty acid synthesis", "protein": "AASDHPPT", "protein_enriched": { "function": "Plays a role in the normal development of the peripheral and central nervous system (PubMed:11062474, PubMed:11159947, PubMed:16022285). Required for the correct localization of aurora kinase AURKA an", "gene_name": "AAAS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG9" }, "relationship_type": "causal", "source_pmcid": "PMC11418321" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "Empagliflozin inhibits SGLT2, increasing urinary glucose excretion, potentially beneficial in heart failure management.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11423468" }, { "confidence": "high", "disease": "Pulmonary valve stenosis (PS)", "glycan_involvement": "Troponin I is glycosylated, which may affect stability and detection.", "mechanism": "Serum cTnI levels used to assess myocardial injury post-balloon valvuloplasty in PS.", "protein": "Cardiac troponin I (cTnI)", "protein_enriched": { "function": "With S4 and S5 plays an important role in translational accuracy. Located at the interface of the 30S and 50S subunits (By similarity)", "gene_name": "rps12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19461" }, "relationship_type": "biomarker", "source_pmcid": "PMC11423468" }, { "confidence": "high", "disease": "Myxomatous mitral valve disease (MMVD)", "glycan_involvement": "ACE glycosylation modulates enzymatic activity and inhibitor binding.", "mechanism": "ACE inhibitors (enalapril) used to block RAS pathway, but aldosterone breakthrough occurs.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11423468" }, { "confidence": "high", "disease": "Myxomatous mitral valve disease (MMVD)", "glycan_involvement": "Aldosterone pathway regulated by glycoprotein receptors.", "mechanism": "Aldosterone levels rise despite ACEi/ARB therapy (aldosterone breakthrough), indicating disease progression.", "protein": "Aldosterone", "relationship_type": "biomarker", "source_pmcid": "PMC11423468" }, { "confidence": "medium", "disease": "Myxomatous mitral valve disease (MMVD)", "glycan_involvement": "Glycosylation affects valve structure, flexibility, and disease susceptibility.", "mechanism": "Degeneration and altered dynamics of mitral valve glycoproteins contribute to regurgitation.", "protein": "Mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11423468" }, { "confidence": "medium", "disease": "Pulmonary valve stenosis (PS)", "glycan_involvement": "Glycosylation modulates extracellular matrix and fibrosis.", "mechanism": "Fibrosis and structural changes in valve glycoproteins lead to stenosis.", "protein": "Pulmonary valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11423468" }, { "confidence": "low", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "Titin glycosylation affects sarcomere elasticity.", "mechanism": "TTN gene variants previously linked to DCM, but not confirmed in UK Dobermans.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "causal", "source_pmcid": "PMC11423468" }, { "confidence": "low", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "PDK4 glycosylation may regulate enzyme activity.", "mechanism": "PDK4 splice-site mutation previously associated with DCM, not confirmed in UK Dobermans.", "protein": "Pyruvate dehydrogenase kinase 4 (PDK4)", "protein_enriched": { "function": "Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehyd", "gene_name": "PDK4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q16654" }, "relationship_type": "causal", "source_pmcid": "PMC11423468" }, { "confidence": "high", "disease": "Obstructive hypertrophic cardiomyopathy (oHCM)", "glycan_involvement": "Glycosylation affects protein folding and sarcomere function.", "mechanism": "A31P MYBPC3 mutation causes oHCM in cats; myosin inhibitors relieve obstruction.", "protein": "Myosin-binding protein C (MYBPC3)", "protein_enriched": { "function": "Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-", "gene_name": "MYBPC3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14896" }, "relationship_type": "causal", "source_pmcid": "PMC11423468" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Chymase glycosylation affects protease activity.", "mechanism": "Chymase contributes to angiotensin II formation in tissue RAS, but ACE is dominant in cats with HCM.", "protein": "Chymase", "protein_enriched": { "function": "Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion", "gene_name": "CMA1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G22573RC", "G02815KT", "G05049YU", "G41247ZX" ], "uniprot_id": "P23946" }, "relationship_type": "biomarker", "source_pmcid": "PMC11423468" }, { "confidence": "medium", "disease": "Liver Steatosis", "glycan_involvement": "Not discussed in this article.", "mechanism": "ALT levels are used in the Hepatic Steatosis Index to predict liver steatosis in CS patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "medium", "disease": "Liver Steatosis", "glycan_involvement": "Not discussed in this article.", "mechanism": "AST levels are used in the Hepatic Steatosis Index to predict liver steatosis in CS patients.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Cushing Syndrome", "glycan_involvement": "Not discussed in this article.", "mechanism": "ALT is elevated in CS and used in HSI to assess metabolic complications.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Cushing Syndrome", "glycan_involvement": "Not discussed in this article.", "mechanism": "AST is elevated in CS and used in HSI to assess metabolic complications.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Not discussed in this article.", "mechanism": "ALT is included in HSI, which incorporates diabetes status for LS risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Not discussed in this article.", "mechanism": "AST is included in HSI, which incorporates diabetes status for LS risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Not discussed in this article.", "mechanism": "ALT is included in HSI, which incorporates BMI for LS risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Not discussed in this article.", "mechanism": "AST is included in HSI, which incorporates BMI for LS risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453202" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "LPL is glycosylated, which affects its folding, stability, and secretion.", "mechanism": "Pathogenic LPL variants reduce triglyceride hydrolysis, leading to elevated plasma triglycerides.", "protein": "Lipoprotein Lipase (LPL)", "relationship_type": "causal", "source_pmcid": "PMC11453235" }, { "confidence": "high", "disease": "Acute Pancreatitis", "glycan_involvement": "Glycosylation of LPL is important for its enzymatic activity.", "mechanism": "Severe hypertriglyceridemia due to LPL deficiency increases risk of pancreatitis.", "protein": "Lipoprotein Lipase (LPL)", "relationship_type": "causal", "source_pmcid": "PMC11453235" }, { "confidence": "high", "disease": "Chylomicronemia Syndrome", "glycan_involvement": "Glycosylation modulates LPL function in chylomicron metabolism.", "mechanism": "LPL mutations impair chylomicron clearance, causing chylomicronemia.", "protein": "Lipoprotein Lipase (LPL)", "relationship_type": "causal", "source_pmcid": "PMC11453235" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "apo C-III is O-glycosylated, affecting its interaction with lipoproteins.", "mechanism": "apo C-III inhibits LPL and hepatic uptake of triglyceride-rich lipoproteins; inhibitors lower triglycerides.", "protein": "Apolipoprotein C-III (apo C-III)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453235" }, { "confidence": "medium", "disease": "Acute Pancreatitis", "glycan_involvement": "O-glycosylation of apo C-III modulates its inhibitory effect on LPL.", "mechanism": "Lowering apo C-III may reduce risk of pancreatitis by decreasing triglycerides.", "protein": "Apolipoprotein C-III (apo C-III)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453235" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "GLP-1 analogs are glycoproteins; glycosylation affects stability and activity.", "mechanism": "GLP-1 analogs lower blood glucose and reduce body weight.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "GIP is a glycoprotein; glycosylation modulates receptor interaction.", "mechanism": "GIP receptor stimulation enhances insulin secretion and glycemic control.", "protein": "GIP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Tirzepatide is a glycoprotein analog; glycosylation impacts pharmacokinetics.", "mechanism": "Dual GLP-1/GIP receptor agonist lowers blood glucose and body weight.", "protein": "Tirzepatide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Dulaglutide is a glycoprotein; glycosylation increases half-life.", "mechanism": "GLP-1 analog lowers blood glucose and body weight.", "protein": "Dulaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Semaglutide is a glycoprotein; glycosylation affects stability.", "mechanism": "GLP-1 analog lowers blood glucose and body weight.", "protein": "Semaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453393" }, { "confidence": "medium", "disease": "Fatty Liver Disease", "glycan_involvement": "Glycosylation enhances therapeutic efficacy.", "mechanism": "GLP-1 analogs improve liver injury in patients with fatty liver and diabetes.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC11453393" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "Glycosylation may affect drug distribution and efficacy.", "mechanism": "Switching to tirzepatide lowers AST, ALT, \u03b3-GTP, indicating improved liver function.", "protein": "Tirzepatide", "relationship_type": "protective", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects long-term glycemic control.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Liver Injury", "glycan_involvement": "Enzymes are glycoproteins; glycosylation affects secretion and stability.", "mechanism": "Serum levels indicate liver injury and response to therapy.", "protein": "AST/ALT/\u03b3-GTP", "relationship_type": "biomarker", "source_pmcid": "PMC11453393" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycoprotein components contribute to index calculation.", "mechanism": "Composite index (includes glycoproteins) estimates liver fibrosis.", "protein": "Fibrosis-4 Index", "relationship_type": "biomarker", "source_pmcid": "PMC11453393" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (PD-1i DM)", "glycan_involvement": "PD-1 glycosylation modulates its cell surface expression and immune checkpoint function.", "mechanism": "PD-1 inhibition leads to aberrant T cell activation against pancreatic islet cells, causing autoimmune diabetes.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC11453514" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (PD-1i DM)", "glycan_involvement": "GAD65 is glycosylated, which may affect its antigenicity and autoantibody recognition.", "mechanism": "Elevated GAD65 autoantibodies indicate autoimmune destruction of pancreatic beta cells.", "protein": "GAD65", "relationship_type": "biomarker", "source_pmcid": "PMC11453514" }, { "confidence": "high", "disease": "Autoimmune diabetes mellitus (PD-1i DM)", "glycan_involvement": "Insulin glycosylation is minimal but may affect stability and secretion.", "mechanism": "Insulin therapy is required due to beta cell destruction and insulin deficiency.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453514" }, { "confidence": "medium", "disease": "Autoimmune diabetes mellitus (PD-1i DM)", "glycan_involvement": "CTLA-4 glycosylation regulates its cell surface expression and immune function.", "mechanism": "Combination of PD-1 and CTLA-4 inhibitors increases risk of autoimmune diabetes via enhanced T cell activation.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC11453514" }, { "confidence": "medium", "disease": "Thyroid abnormalities", "glycan_involvement": "Glycosylation affects PD-1 function in immune regulation.", "mechanism": "PD-1 inhibition can trigger autoimmune thyroid dysfunction.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC11453514" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation of PD-1 may influence drug binding and efficacy.", "mechanism": "Pembrolizumab (PD-1 inhibitor) is used to treat gastric cancer by enhancing anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453514" }, { "confidence": "medium", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Glycosylation may affect GAD65 autoantibody binding.", "mechanism": "Presence of GAD65 autoantibodies is associated with increased risk of DKA in autoimmune diabetes.", "protein": "GAD65", "relationship_type": "biomarker", "source_pmcid": "PMC11453514" }, { "confidence": "high", "disease": "Multiple Symmetric Lipomatosis (MSL)", "glycan_involvement": "Leptin is a glycoprotein; glycosylation is required for its secretion and stability.", "mechanism": "Leptin deficiency in MFN2-related MSL contributes to abnormal fat deposition; leptin replacement reduces lipoma size and improves metabolic parameters.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453523" }, { "confidence": "high", "disease": "Multiple Symmetric Lipomatosis (MSL)", "glycan_involvement": "Metreleptin is glycosylated, mimicking endogenous leptin's activity.", "mechanism": "Metreleptin (recombinant leptin) administration leads to reduction in trunk fat mass and lipoma size in MSL patients.", "protein": "Metreleptin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453523" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation of leptin is essential for receptor binding and function.", "mechanism": "Leptin replacement improves insulin sensitivity and reduces insulin AUC in MSL patients.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453523" }, { "confidence": "medium", "disease": "Fatty liver", "glycan_involvement": "Glycosylation affects leptin's bioactivity.", "mechanism": "Leptin replacement reduces fatty liver markers (AST) in MSL patients.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453523" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation required for leptin's metabolic effects.", "mechanism": "Leptin replacement lowers fasting and OGTT triglyceride levels in MSL patients.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453523" }, { "confidence": "high", "disease": "PCOS", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "FGF21 levels are elevated in adolescent girls with PCOS compared to controls, reflecting altered metabolic signaling.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Potential glycoprotein; glycosylation status not specified.", "mechanism": "DBI levels are lower in OC-treated PCOS girls compared to controls and spiomet-treated girls, suggesting treatment-specific modulation.", "protein": "DBI", "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "high", "disease": "Liver damage (elevated liver enzymes)", "glycan_involvement": "METRNL is a glycoprotein; glycosylation may regulate secretion/function.", "mechanism": "Circulating METRNL levels correlate with ALT and GGT only in OC-treated girls, suggesting a response to hepatic changes.", "protein": "METRNL", "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "high", "disease": "Liver damage (elevated liver enzymes)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "ALT is elevated during OC treatment, indicating hepatic stress.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "high", "disease": "Liver damage (elevated liver enzymes)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability.", "mechanism": "GGT is elevated during OC treatment, indicating hepatic stress.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may affect FGF21's metabolic signaling.", "mechanism": "FGF21 is associated with MAFLD and altered hepatic function.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "No significant difference in METRNL levels between PCOS and controls.", "protein": "METRNL", "relationship_type": "biomarker", "source_pmcid": "PMC11453617" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "N-glycosylation may affect ALT stability and secretion.", "mechanism": "Elevated ALT reflects hepatocellular injury associated with steatosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation may modulate ALT serum levels.", "mechanism": "ALT elevation indicates ongoing liver damage in cirrhosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "N-glycosylation influences AST secretion and activity.", "mechanism": "AST elevation is indicative of hepatocyte injury in steatosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation may affect AST serum half-life.", "mechanism": "AST is increased in cirrhosis due to hepatocellular and mitochondrial damage.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "N-glycosylation is essential for GGT activity and stability.", "mechanism": "GGT elevation reflects oxidative stress and cholestasis in steatosis.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "N-glycosylation modulates GGT function and serum levels.", "mechanism": "GGT is increased in cirrhosis due to biliary tract involvement.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC11453671" }, { "confidence": "high", "disease": "Male infertility due to Sertoli cell deficiency", "glycan_involvement": "FSTL3 is a glycoprotein; glycosylation may affect its stability and interaction with activin.", "mechanism": "FSTL3 inhibits activin signaling, which restricts Sertoli cell proliferation; deletion of FSTL3 increases Sertoli cell numbers and spermatogenesis, suggesting FSTL3 inhibition could treat infertility caused by low Sertoli cell counts.", "protein": "Follistatin like 3 (FSTL3)", "protein_enriched": { "function": "Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway", "gene_name": "HCAR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BXC0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11453784" }, { "confidence": "medium", "disease": "Male infertility due to Sertoli cell deficiency", "glycan_involvement": "Activin is a glycoprotein; glycosylation may modulate receptor binding.", "mechanism": "Activin promotes Sertoli cell proliferation; its activity is regulated by FSTL3.", "protein": "Activin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11453784" }, { "confidence": "high", "disease": "Congenital Generalized Lipodystrophy (CGL)", "glycan_involvement": "Leptin is a glycoprotein; its secretion and function depend on proper glycosylation.", "mechanism": "Leptin deficiency is characteristic of CGL due to loss of adipose tissue, leading to metabolic complications.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC11453912" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "Elevated HbA1c reflects chronic hyperglycemia in diabetes.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC11453912" }, { "confidence": "medium", "disease": "Urinary bladder paraganglioma", "glycan_involvement": "N-glycosylation affects stability and secretion of Chromogranin A.", "mechanism": "Chromogranin A is secreted by neuroendocrine tumors including paragangliomas and can be detected in plasma.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454002" }, { "confidence": "medium", "disease": "Urinary bladder paraganglioma", "glycan_involvement": "Metanephrines are metabolites, but derived from glycoprotein hormone pathways.", "mechanism": "Elevated plasma and urinary metanephrines are diagnostic for paraganglioma due to catecholamine secretion.", "protein": "Metanephrines (MN)", "relationship_type": "biomarker", "source_pmcid": "PMC11454002" }, { "confidence": "high", "disease": "Thyroid Storm", "glycan_involvement": "TRAb is an immunoglobulin glycoprotein; glycosylation affects antibody function and clearance.", "mechanism": "Elevated TRAb indicates autoimmune hyperthyroidism, a precipitating factor for thyroid storm.", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "high", "disease": "Thyroid Storm", "glycan_involvement": "TSH is a glycoprotein hormone; glycosylation is essential for secretion and receptor binding.", "mechanism": "Suppressed TSH is a diagnostic marker for thyrotoxicosis and thyroid storm.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "high", "disease": "Thyroid Storm", "glycan_involvement": "T4 is transported by glycoprotein carriers (e.g., TBG); glycosylation affects stability.", "mechanism": "Elevated free T4 confirms thyrotoxicosis in thyroid storm.", "protein": "Free Thyroxine (T4)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "medium", "disease": "Acute Liver Failure", "glycan_involvement": "N-glycosylation is critical for coagulation factor secretion and function.", "mechanism": "INR elevation reflects impaired synthesis of glycoprotein coagulation factors in liver failure.", "protein": "Coagulation Factors (e.g., Factor VIII)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "Glycosylation modulates immunogenicity and pathogenicity of autoantibodies.", "mechanism": "Autoimmunity (elevated TRAb) may co-occur with other autoimmune diseases such as autoimmune hepatitis.", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC11454145" }, { "confidence": "high", "disease": "Hyperthyroidism", "glycan_involvement": "Glycosylation is required for TSH bioactivity.", "mechanism": "Low TSH is a hallmark of hyperthyroidism.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "high", "disease": "Hyperthyroidism", "glycan_involvement": "Glycosylation influences TRAb-receptor interactions.", "mechanism": "TRAb stimulates the TSH receptor, causing hyperthyroidism.", "protein": "Thyroid Stimulating Hormone Receptor Antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC11454145" }, { "confidence": "medium", "disease": "Toxic Hepatitis", "glycan_involvement": "N-glycosylation is essential for factor secretion.", "mechanism": "Liver injury impairs synthesis of glycoprotein coagulation factors, reflected in INR.", "protein": "Coagulation Factors (e.g., Factor VIII)", "relationship_type": "biomarker", "source_pmcid": "PMC11454145" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "FGF-21 is a glycoprotein; glycosylation affects stability and bioactivity.", "mechanism": "FGF-21 analogues improve liver histology, reduce hepatic fat, inflammation, and fibrosis.", "protein": "FGF-21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may modulate receptor binding and pharmacokinetics.", "mechanism": "FGF-21 analogues significantly reduce hepatic fat fraction.", "protein": "FGF-21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation influences FGF-21 secretion and activity.", "mechanism": "FGF-21 analogues improve fibrosis stage without worsening MASH.", "protein": "FGF-21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation may affect FGF-21's anti-inflammatory properties.", "mechanism": "FGF-21 analogues decrease liver enzymes (ALT, AST, GGT, ALP), markers of inflammation.", "protein": "FGF-21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Pro-C3 is glycosylated; glycan structure affects ECM deposition and turnover.", "mechanism": "Pro-C3 levels decrease with FGF-21 analogue therapy, reflecting reduced fibrosis.", "protein": "Pro-C3", "relationship_type": "biomarker", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Panel proteins are glycosylated; glycosylation impacts serum detection and function.", "mechanism": "ELF score decreases with FGF-21 analogues, indicating fibrosis improvement.", "protein": "ELF panel (includes PIIINP, hyaluronic acid, TIMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC11454154" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may modulate FGF-21's protective effects.", "mechanism": "FGF-21 analogues trend toward MASH resolution, though not statistically significant for composite outcome.", "protein": "FGF-21", "relationship_type": "protective", "source_pmcid": "PMC11454154" }, { "confidence": "high", "disease": "Hepatic stiffness", "glycan_involvement": "Glycosylation may affect FGF-21's tissue distribution.", "mechanism": "FGF-21 analogues reduce liver stiffness, a surrogate for fibrosis.", "protein": "FGF-21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454154" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation influences Pro-C3's ECM interactions.", "mechanism": "Pro-C3 reduction correlates with improved MASH features.", "protein": "Pro-C3", "relationship_type": "biomarker", "source_pmcid": "PMC11454154" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation affects biomarker reliability.", "mechanism": "ELF score reduction reflects improvement in MASH pathology.", "protein": "ELF panel", "relationship_type": "biomarker", "source_pmcid": "PMC11454154" }, { "confidence": "medium", "disease": "acute decompensated liver cirrhosis", "glycan_involvement": "AFP glycosylation patterns can change in liver disease.", "mechanism": "AFP is often elevated in liver disease and hepatocellular carcinoma; in this case, it was measured to rule out malignancy.", "protein": "alpha fetoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11454279" }, { "confidence": "medium", "disease": "hypercalcemia", "glycan_involvement": "PTHrP is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "PTHrP can cause hypercalcemia in malignancy; mild elevation here suggests non-malignant causes.", "protein": "parathyroid hormone related peptide (PTHrP)", "relationship_type": "biomarker", "source_pmcid": "PMC11454279" }, { "confidence": "medium", "disease": "acute decompensated liver cirrhosis", "glycan_involvement": "Albumin glycosylation may be altered in liver disease.", "mechanism": "Hypoalbuminemia is common in liver failure and affects calcium binding.", "protein": "albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11454279" }, { "confidence": "high", "disease": "Mauriac syndrome", "glycan_involvement": "IGF-1 is a glycoprotein; glycosylation affects its stability and bioactivity.", "mechanism": "Low IGF-1 levels reflect impaired growth and delayed puberty in Mauriac syndrome due to poor glycemic control.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin; reflects glucose exposure.", "mechanism": "Elevated HbA1c indicates chronic hyperglycemia and poor glycemic control.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Mauriac syndrome", "glycan_involvement": "Insulin analogs may be glycosylated to improve pharmacokinetics.", "mechanism": "Insulin deficiency or poor access leads to Mauriac syndrome; restoration reverses symptoms.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Growth failure", "glycan_involvement": "Glycosylation modulates IGF-1 receptor binding and activity.", "mechanism": "Low IGF-1 due to poor glycemic control impairs growth.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "causal", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Glycosylation of insulin analogs may affect therapeutic efficacy.", "mechanism": "Insulin deficiency leads to lipolysis, ketosis, and DKA.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11454729" }, { "confidence": "medium", "disease": "Delayed pubertal maturation", "glycan_involvement": "Glycosylation affects IGF-1 stability and endocrine function.", "mechanism": "Low IGF-1 is associated with delayed puberty in poorly controlled T1DM.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Mauriac syndrome", "glycan_involvement": "Reflects glycation status of hemoglobin.", "mechanism": "High HbA1c is a marker of chronic hyperglycemia, a risk factor for Mauriac syndrome.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC11454729" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation of insulin analogs may affect lipid metabolism.", "mechanism": "Insulin deficiency promotes lipolysis and hyperlipidemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11454729" }, { "confidence": "medium", "disease": "Transaminitis", "glycan_involvement": "Glycosylation of insulin analogs may influence hepatic effects.", "mechanism": "Insulin deficiency and hyperglycemia lead to hepatic glycogen deposition and liver dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11454729" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation affects IGF-1 half-life and activity.", "mechanism": "Low IGF-1 is common in poorly controlled T1DM.", "protein": "Insulin-like growth factor-1 (IGF-1)", "protein_enriched": { "function": "The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C", "gene_name": "IGF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05019" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454729" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation affects DPP-4 stability and activity.", "mechanism": "DPP-4 inhibitors improve glycemic control by preventing incretin degradation.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454785" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation modulates SGLT2 membrane localization and function.", "mechanism": "SGLT2 inhibitors reduce renal glucose reabsorption, lowering blood glucose.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454785" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycation (not classical glycosylation) is the basis for HbA1c formation.", "mechanism": "HbA1c reflects average blood glucose via non-enzymatic glycation.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may affect DPP-4 clearance and renal interactions.", "mechanism": "DPP-4 inhibitors are effective in patients with reduced renal function.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may influence SGLT2 renal expression.", "mechanism": "SGLT2 inhibitors are less effective in patients with reduced eGFR.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation may affect AST secretion and stability.", "mechanism": "AST levels decrease with SGLT2 inhibitor therapy, indicating improved liver function.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation may affect ALT secretion and stability.", "mechanism": "ALT levels decrease with SGLT2 inhibitor therapy, indicating improved liver function.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Glycation of hemoglobin is a direct result of elevated glucose.", "mechanism": "HbA1c increases with chronic hyperglycemia.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation regulates DPP-4 activity.", "mechanism": "DPP-4 activity correlates with metabolic status.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation affects SGLT2 trafficking.", "mechanism": "SGLT2 expression is upregulated in diabetes.", "protein": "Sodium-glucose cotransporter-2 (SGLT2)", "protein_enriched": { "function": "Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intra", "gene_name": "SLC4A4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454785" }, { "confidence": "high", "disease": "Autoimmune thyroiditis", "glycan_involvement": "TPO is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "Elevated anti-TPO antibodies indicate autoimmune destruction of thyroid tissue.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC11454794" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "TSH is a glycoprotein; glycosylation modulates receptor binding and bioactivity.", "mechanism": "Elevated TSH reflects reduced thyroid hormone production.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11454794" }, { "confidence": "medium", "disease": "Pericardial effusion", "glycan_involvement": "Glycosylation of TSH affects its stability and activity, influencing disease severity.", "mechanism": "Severe hypothyroidism (high TSH) leads to pericardial effusion via altered capillary permeability and reduced lymphatic drainage.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC11454794" }, { "confidence": "medium", "disease": "Cardiac tamponade", "glycan_involvement": "TSH glycosylation may affect hormone clearance and disease progression.", "mechanism": "Extreme hypothyroidism (markedly elevated TSH) can progress to cardiac tamponade due to massive pericardial effusion.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC11454794" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "Glycosylation of TPO influences immune response and antibody binding.", "mechanism": "Autoantibodies against TPO cause thyroid dysfunction.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "causal", "source_pmcid": "PMC11454794" }, { "confidence": "high", "disease": "PCOS", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "FGF21 levels are elevated in adolescent girls with PCOS compared to controls, indicating metabolic dysregulation.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454877" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may modulate FGF21's bioactivity and half-life.", "mechanism": "FGF21 is associated with altered hepatic function and systemic dysmetabolism in MAFLD.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454877" }, { "confidence": "medium", "disease": "PCOS", "glycan_involvement": "DBI is not a classical glycoprotein; glycan involvement is minimal or unclear.", "mechanism": "DBI levels are lower in OC-treated PCOS girls compared to controls and spiomet-treated girls, suggesting treatment-specific modulation.", "protein": "DBI", "relationship_type": "biomarker", "source_pmcid": "PMC11454877" }, { "confidence": "low", "disease": "PCOS", "glycan_involvement": "METRNL is a glycoprotein; glycosylation may affect secretion.", "mechanism": "No significant difference in METRNL levels between PCOS and controls; not a primary biomarker for PCOS in this context.", "protein": "METRNL", "relationship_type": "biomarker", "source_pmcid": "PMC11454877" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may regulate METRNL's stability and function.", "mechanism": "Serum ALT and GGT (liver enzymes) correlate with METRNL only in OC-treated girls, suggesting METRNL responds to hepatic stress.", "protein": "METRNL", "relationship_type": "biomarker", "source_pmcid": "PMC11454877" }, { "confidence": "high", "disease": "Hereditary Hemochromatosis", "glycan_involvement": "HFE is a glycoprotein; glycosylation affects its stability and cell surface expression.", "mechanism": "Mutations in HFE disrupt iron homeostasis, leading to iron overload.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "high", "disease": "Diabetes Mellitus (Bronze Diabetes)", "glycan_involvement": "Glycosylation of HFE may modulate its interaction with transferrin receptor and iron regulation.", "mechanism": "Iron overload from HFE mutation damages pancreatic beta cells, impairing insulin secretion.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "high", "disease": "Hereditary Hemochromatosis", "glycan_involvement": "Hepcidin is glycosylated; glycosylation affects its secretion and stability.", "mechanism": "HFE mutation leads to decreased hepcidin expression, increasing iron absorption.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "high", "disease": "Diabetes Mellitus (Bronze Diabetes)", "glycan_involvement": "Insulin is glycosylated; glycosylation is essential for proper folding and secretion.", "mechanism": "Iron overload impairs insulin secretion and beta-cell function.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11454890" }, { "confidence": "medium", "disease": "Diabetes Mellitus (Bronze Diabetes)", "glycan_involvement": "C-peptide is derived from proinsulin, which is glycosylated.", "mechanism": "C-peptide levels reflect endogenous insulin production; reduced in beta-cell dysfunction.", "protein": "C-Peptide", "relationship_type": "biomarker", "source_pmcid": "PMC11454890" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "GAD65 is glycosylated; glycosylation may affect antigenicity.", "mechanism": "GAD65 autoantibodies are negative, helping distinguish T2DM from autoimmune diabetes.", "protein": "GAD65", "relationship_type": "biomarker", "source_pmcid": "PMC11454890" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation of HFE may affect tissue distribution.", "mechanism": "Iron overload from HFE mutation can deposit in cardiac tissue, causing dysfunction.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "medium", "disease": "Hepatic Fibrosis/Cirrhosis", "glycan_involvement": "Glycosylation may affect HFE's hepatic localization.", "mechanism": "Iron overload damages liver tissue, leading to fibrosis and cirrhosis.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "low", "disease": "Arthropathy", "glycan_involvement": "Glycosylation may affect HFE's tissue targeting.", "mechanism": "Iron deposition in joints leads to arthropathy.", "protein": "HFE", "protein_enriched": { "function": "Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin", "gene_name": "HFE", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G27058EU", "G62765YT", "G63041LO", "G49108TO" ], "uniprot_id": "Q30201" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "medium", "disease": "Pancreatic Beta-cell Dysfunction", "glycan_involvement": "Glycosylation affects hepcidin's bioactivity.", "mechanism": "Low hepcidin increases iron uptake in pancreas, damaging beta cells.", "protein": "Hepcidin", "protein_enriched": { "function": "Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading", "gene_name": "HAMP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P81172" }, "relationship_type": "causal", "source_pmcid": "PMC11454890" }, { "confidence": "high", "disease": "Neuroendocrine tumor (NET)", "glycan_involvement": "CEA is a heavily glycosylated cell adhesion molecule; altered glycosylation may affect tumor progression and immune recognition.", "mechanism": "Elevated CEA levels indicate presence of NET and liver metastasis.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC11454950" }, { "confidence": "high", "disease": "Neuroendocrine tumor (NET)", "glycan_involvement": "CA19-9 is a glycan epitope on glycoproteins; aberrant glycosylation increases its expression in malignancy.", "mechanism": "High CA19-9 levels are associated with NET and liver involvement.", "protein": "CA19-9 (Sialyl-Lewis a antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC11454950" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "AFP is N-glycosylated; glycan changes may affect its serum levels and diagnostic utility.", "mechanism": "AFP is used to screen for liver pathology; low levels here help exclude hepatocellular carcinoma.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454950" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "Transferrin glycosylation status can be altered in liver disease, affecting iron transport.", "mechanism": "Transferrin saturation is used to assess iron overload in hemochromatosis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454950" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "Ferritin is glycosylated; glycan modifications may influence its stability and serum levels.", "mechanism": "Elevated ferritin is a marker of iron overload, seen in hemochromatosis and liver disease.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454950" }, { "confidence": "high", "disease": "Hashimoto thyroiditis", "glycan_involvement": "Glycosylation of TPO may affect antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against TPO indicate autoimmune destruction of thyroid tissue.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "high", "disease": "Hashimoto thyroiditis", "glycan_involvement": "Glycosylation influences thyroglobulin structure and immune recognition.", "mechanism": "Autoantibodies against thyroglobulin are markers of autoimmune thyroid disease.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "TSH glycosylation modulates receptor binding and bioactivity.", "mechanism": "Elevated TSH reflects thyroid hormone deficiency due to gland dysfunction.", "protein": "TSH (Thyroid Stimulating Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "Altered glycosylation may enhance immunogenicity.", "mechanism": "Thyroglobulin antibodies are present in autoimmune hypothyroidism.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "medium", "disease": "Adrenal insufficiency", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against 21-hydroxylase are markers for autoimmune adrenal insufficiency (negative in this case).", "protein": "21-hydroxylase", "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "medium", "disease": "Hyperlipidemia (elevated LDL)", "glycan_involvement": "LDL glycosylation affects clearance and receptor interaction.", "mechanism": "Elevated LDL is a metabolic consequence of hypothyroidism.", "protein": "LDL (Low-Density Lipoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC11454957" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "ALT is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "ALT elevation indicates hepatocellular injury in DILI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455116" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "AST is a glycoprotein; glycosylation affects its secretion and activity.", "mechanism": "AST elevation indicates hepatocellular injury in DILI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455116" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may influence ALT serum levels.", "mechanism": "Marked ALT elevation is a feature of acute liver failure.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455116" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may influence AST serum levels.", "mechanism": "Marked AST elevation is a feature of acute liver failure.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455116" }, { "confidence": "high", "disease": "Severe hypothyroidism", "glycan_involvement": "TSH glycosylation affects its stability and bioactivity.", "mechanism": "Elevated TSH indicates thyroid hormone deficiency.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11455142" }, { "confidence": "medium", "disease": "Severe hypothyroidism", "glycan_involvement": "TBG glycosylation modulates hormone binding.", "mechanism": "TBG levels influence free thyroid hormone availability.", "protein": "Thyroxine-binding globulin (TBG)", "protein_enriched": { "function": "Major thyroid hormone transport protein in serum", "gene_name": "SERPINA7", "glycan_count": 41, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10846ZT", "G11911BT", "G12341GU", "G14547CB", "G15169WU", "G22310AV", "G25418HZ", "G26330YA", "G27947YN", "G31986NC", "G40574BA", "G40834TG", "G45395BF", "G47518TP", "G48414YA", "G56518TU", "G57776ZS", "G59626AS", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G86880BF", "G94470IW", "G95865ZB", "G10486CT", "G22140GZ", "G37881RL", "G43223CG", "G50045TK", "G52527GH", "G75983OB", "G88374WZ", "G92551JA", "G43417UB" ], "uniprot_id": "P05543" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455142" }, { "confidence": "medium", "disease": "Hashimoto's thyroiditis", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "Autoantibodies (IgG) target thyroid antigens, causing autoimmune destruction.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11455142" }, { "confidence": "high", "disease": "Male infertility due to paucity of Sertoli cells", "glycan_involvement": "FSTL3 is a glycoprotein; glycosylation may affect its stability and inhibitory function.", "mechanism": "FSTL3 inhibits activin signalling, which limits Sertoli cell proliferation; deletion of FSTL3 increases Sertoli cell numbers and may alleviate infertility caused by low Sertoli cell counts.", "protein": "Follistatin like 3 (FSTL3)", "protein_enriched": { "function": "Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway", "gene_name": "HCAR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BXC0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11455180" }, { "confidence": "high", "disease": "Testicular hypertrophy", "glycan_involvement": "Glycosylation of FSTL3 may regulate its inhibitory activity on activin.", "mechanism": "FSTL3 deletion leads to increased testicular size due to enhanced spermatogenesis and Sertoli cell proliferation.", "protein": "Follistatin like 3 (FSTL3)", "protein_enriched": { "function": "Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway", "gene_name": "HCAR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BXC0" }, "relationship_type": "causal", "source_pmcid": "PMC11455180" }, { "confidence": "medium", "disease": "Male infertility due to paucity of Sertoli cells", "glycan_involvement": "Activin is a glycoprotein; glycosylation may affect receptor binding and signalling.", "mechanism": "Activin promotes Sertoli cell proliferation; its activity is suppressed by FSTL3.", "protein": "Activin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11455180" }, { "confidence": "medium", "disease": "Male infertility due to paucity of Sertoli cells", "glycan_involvement": "Glycosylation may influence FSTL3 secretion and activity.", "mechanism": "FSTL3 expression levels may indicate Sertoli cell proliferation status and testicular function.", "protein": "Follistatin like 3 (FSTL3)", "protein_enriched": { "function": "Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway", "gene_name": "HCAR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BXC0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455180" }, { "confidence": "medium", "disease": "Male infertility due to paucity of Sertoli cells", "glycan_involvement": "Glycosylation may modulate FSTL3's inhibitory effect.", "mechanism": "FSTL3 maintains Sertoli cell proliferation arrest postnatally, preventing over-proliferation.", "protein": "Follistatin like 3 (FSTL3)", "protein_enriched": { "function": "Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway", "gene_name": "HCAR1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9BXC0" }, "relationship_type": "protective", "source_pmcid": "PMC11455180" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation may affect ALT stability and serum detection.", "mechanism": "ALT elevation indicates liver cell injury during ketoconazole therapy.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation may modulate AST secretion and half-life.", "mechanism": "AST elevation correlates with increased risk of liver toxicity from ketoconazole.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation critical for ALP stability and activity.", "mechanism": "ALP rises after AST during liver injury in ketoconazole-treated patients.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "medium", "disease": "Cushing's Syndrome", "glycan_involvement": "N-glycosylation regulates CBG affinity for cortisol.", "mechanism": "CBG binds cortisol; altered levels may affect cortisol measurement and interpretation.", "protein": "CBG", "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "medium", "disease": "Cushing's Syndrome", "glycan_involvement": "Glycosylation may influence ALT clearance.", "mechanism": "ALT may improve in some patients due to cortisol reduction after ketoconazole therapy.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "medium", "disease": "Cushing's Syndrome", "glycan_involvement": "Glycosylation may affect AST serum levels.", "mechanism": "AST baseline levels predict risk of hepatotoxicity during Cushing's treatment.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "medium", "disease": "Cushing's Syndrome", "glycan_involvement": "N-glycosylation essential for ALP function.", "mechanism": "ALP changes may reflect liver status during cortisol-lowering therapy.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11455232" }, { "confidence": "medium", "disease": "Hepatocellular Adenoma (HCA)", "glycan_involvement": "Glycosylation of estrogen receptor may affect receptor stability and signaling.", "mechanism": "Estrogen receptor positivity in HCA suggests hormone-driven tumor growth.", "protein": "Estrogen Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC11455260" }, { "confidence": "medium", "disease": "Hepatocellular Adenoma (HCA)", "glycan_involvement": "Glycosylation may modulate androgen receptor function and hormone binding.", "mechanism": "Androgen receptor positivity in HCA indicates possible androgen-driven tumor growth, especially in context of exogenous hormone therapy.", "protein": "Androgen Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC11455260" }, { "confidence": "medium", "disease": "Malignant Transformation of HCA", "glycan_involvement": "Glycosylation can affect beta-catenin stability and localization.", "mechanism": "Beta-catenin activation is associated with increased risk of malignant transformation in HCA; absence (negative status) may indicate lower risk.", "protein": "Beta-catenin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11455260" }, { "confidence": "high", "disease": "Autoimmune hypothyroidism (Hashimoto's thyroiditis)", "glycan_involvement": "TPO is N-glycosylated; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Anti-TPO antibodies indicate autoimmune destruction of thyroid tissue.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC11455281" }, { "confidence": "high", "disease": "Autoimmune hypothyroidism (Hashimoto's thyroiditis)", "glycan_involvement": "TSH is a heavily N-glycosylated hormone; glycosylation is essential for bioactivity and stability.", "mechanism": "Elevated TSH reflects loss of thyroid hormone feedback due to gland destruction.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11455281" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Altered glycosylation may modulate TPO immunogenicity.", "mechanism": "Autoimmune hypothyroidism due to anti-TPO antibodies leads to myopathy and rare rhabdomyolysis.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "causal (indirect)", "source_pmcid": "PMC11455281" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation required for TSH function.", "mechanism": "Elevated TSH signals hypothyroidism, which predisposes to muscle breakdown.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker (indirect)", "source_pmcid": "PMC11455281" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation may affect TPO's immunogenicity.", "mechanism": "Autoimmune hypothyroidism (anti-TPO) can cause rhabdomyolysis, leading to AKI.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "causal (indirect)", "source_pmcid": "PMC11455281" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation required for TSH function.", "mechanism": "Elevated TSH reflects hypothyroidism, which can lead to muscle and renal complications.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker (indirect)", "source_pmcid": "PMC11455281" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "CRP is heavily glycosylated, affecting its stability and function.", "mechanism": "CRP levels reflect systemic inflammation in obesity and liver disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased risk of MASH.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "AST is glycosylated, influencing its serum stability.", "mechanism": "AST levels are used in APRI and FIB-4 indices to assess liver fibrosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "ALT glycosylation affects its release and detection.", "mechanism": "ALT is a marker of hepatocellular injury and fibrosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate interactions in liver disease.", "mechanism": "Platelet count is used in APRI and FIB-4 indices for fibrosis assessment.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Insulin glycosylation affects its receptor binding and clearance.", "mechanism": "Insulin levels (HOMA-IR) correlate with liver fat and fibrosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates CRP's half-life and activity.", "mechanism": "CRP is elevated in obesity and reflects chronic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "Glycosylation impacts AST's serum levels.", "mechanism": "AST is elevated in MASH and used in fibrosis indices.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "Platelet glycoproteins mediate immune and fibrotic responses.", "mechanism": "Platelet count inversely correlates with fibrosis severity in MASH.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Insulin glycosylation affects metabolic signaling.", "mechanism": "Insulin resistance is common in obesity and linked to liver fat.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455283" }, { "confidence": "medium", "disease": "Turner syndrome", "glycan_involvement": "IL-6 is N-glycosylated, which affects its stability and secretion.", "mechanism": "Elevated IL-6 indicates increased inflammation in TS youth, associated with metabolic risk.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "medium", "disease": "Turner syndrome", "glycan_involvement": "CRP is N-glycosylated, influencing its clearance and function.", "mechanism": "Elevated CRP reflects systemic inflammation in TS, linked to metabolic dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL contains glycoprotein ApoB, whose glycosylation modulates LDL metabolism.", "mechanism": "Elevated LDL-C observed in TS youth, indicating increased risk for dyslipidemia.", "protein": "Low-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "medium", "disease": "Metabolic dysfunction", "glycan_involvement": "Glycosylation affects CRP's inflammatory activity.", "mechanism": "High CRP levels in TS youth are associated with increased visceral adiposity and metabolic risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "medium", "disease": "Metabolic dysfunction", "glycan_involvement": "N-glycosylation modulates IL-6 bioactivity.", "mechanism": "IL-6 elevation correlates with increased visceral fat and metabolic risk in TS.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "ApoB glycosylation affects LDL receptor binding and clearance.", "mechanism": "Elevated LDL-C in TS may contribute to hypertension risk.", "protein": "Low-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "low", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation of LDL components influences insulin sensitivity.", "mechanism": "Dyslipidemia (elevated LDL-C) in TS is a risk factor for T2DM.", "protein": "Low-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (suggested by elevated AST/ALT)", "glycan_involvement": "CRP glycosylation modulates hepatic clearance.", "mechanism": "Elevated CRP may reflect hepatic inflammation in TS youth with high AST/ALT.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11455364" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated ALP indicates cholestatic or hepatocellular injury in AIH.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "GGT is a glycoprotein; glycosylation modulates its secretion and activity.", "mechanism": "Elevated GGT reflects liver injury and is used to monitor AIH activity.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its serum half-life.", "mechanism": "Elevated AST is a marker of hepatocellular injury in AIH.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "ALT is a glycoprotein; glycosylation influences its stability.", "mechanism": "ALT elevation is a sensitive marker of hepatocellular injury in AIH.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "medium", "disease": "Toxic hepatitis", "glycan_involvement": "Glycosylation affects ALP serum levels.", "mechanism": "ALP elevation can indicate toxic liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "medium", "disease": "Toxic hepatitis", "glycan_involvement": "Glycosylation modulates GGT secretion.", "mechanism": "GGT is elevated in toxic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11455495" }, { "confidence": "medium", "disease": "Corneal disease", "glycan_involvement": "Glycosylation affects graft survival and immune response.", "mechanism": "Corneal glycoproteins are essential for tissue integrity and transplantation success.", "protein": "Corneal tissue glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11459890" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "Glycosylation modulates leukocyte adhesion and migration.", "mechanism": "Elevated leukocyte counts in ACLF patients indicate immune activation.", "protein": "Leukocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11459890" }, { "confidence": "medium", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Glycosylation may affect enzyme stability and release.", "mechanism": "AST levels reflect tissue damage after organ procurement.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC11459890" }, { "confidence": "medium", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Glycosylation may affect enzyme secretion.", "mechanism": "ALT levels indicate hepatic injury post-transplant or ischemia.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC11459890" }, { "confidence": "low", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Statins may modulate glycoprotein-mediated endothelial function.", "mechanism": "Statins improve microcirculation and reduce organ damage.", "protein": "Statins", "relationship_type": "protective", "source_pmcid": "PMC11459890" }, { "confidence": "low", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "May affect glycoprotein antioxidant pathways.", "mechanism": "Melatonin reduces oxidative stress in organ preconditioning.", "protein": "Melatonin", "relationship_type": "protective", "source_pmcid": "PMC11459890" }, { "confidence": "low", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "May preserve glycoprotein structure under stress.", "mechanism": "N-acetylcysteine reduces oxidative stress and tissue damage.", "protein": "N-acetylcysteine", "relationship_type": "protective", "source_pmcid": "PMC11459890" }, { "confidence": "low", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Steroids may regulate glycoprotein-mediated inflammation.", "mechanism": "Steroids mitigate ischemic injury during organ procurement.", "protein": "Steroids", "relationship_type": "protective", "source_pmcid": "PMC11459890" }, { "confidence": "medium", "disease": "Organ transplantation outcome", "glycan_involvement": "Glycosylation patterns influence immune acceptance.", "mechanism": "Quality of corneal glycoproteins affects transplantation success.", "protein": "Corneal tissue glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11459890" }, { "confidence": "low", "disease": "Infection (post-operative)", "glycan_involvement": "Glycosylation modulates leukocyte function.", "mechanism": "Leukocyte glycoproteins mediate immune response to infection.", "protein": "Leukocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11459890" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in IR and predicts T2D risk; reflects low-grade inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11475114" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "IL-6 is glycosylated, which affects secretion and receptor binding.", "mechanism": "IL-6 is elevated in IR and predicts T2D; involved in inflammatory pathways.", "protein": "Interleukin-6", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11475114" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Adiponectin is O-glycosylated, required for multimerization and activity.", "mechanism": "Low adiponectin predicts IR and T2D; enhances insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Leptin is glycosylated, which affects secretion and receptor interaction.", "mechanism": "Leptin resistance is linked to IR and T2D; high leptin may predict risk in men.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Insulin resistance (IR)", "glycan_involvement": "Composite N-acetyl signals from acute-phase glycoproteins.", "mechanism": "GlycA reflects systemic inflammation and correlates with IR.", "protein": "Glycoprotein acetyls (GlycA)", "relationship_type": "biomarker", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "TNF-\u03b1 is glycosylated, influencing stability and activity.", "mechanism": "Elevated TNF-\u03b1 is associated with IR and increased T2D risk.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting secretion and function.", "mechanism": "Elevated IL-1\u03b2 is associated with increased T2D risk.", "protein": "Interleukin-1\u03b2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "IL-18 is glycosylated, influencing secretion.", "mechanism": "Elevated IL-18 is associated with increased T2D risk.", "protein": "Interleukin-18", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11475114" }, { "confidence": "medium", "disease": "Insulin resistance (IR)", "glycan_involvement": "CD36 is N-glycosylated, affecting membrane localization.", "mechanism": "Elevated sCD36 correlates with IR; involved in lipid metabolism.", "protein": "Soluble CD36", "relationship_type": "biomarker", "source_pmcid": "PMC11475114" }, { "confidence": "low", "disease": "Insulin resistance (IR)", "glycan_involvement": "Procalcitonin is glycosylated, influencing stability.", "mechanism": "Procalcitonin is elevated in IR; reflects inflammation.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11475114" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates PD-L1 stability and immune recognition.", "mechanism": "PD-L1 expression on tumor cells predicts response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11477479" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Altered O-glycosylation exposes tumor-associated epitopes.", "mechanism": "Aberrant glycosylation of MUC1 is associated with tumor progression and immune evasion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "medium", "disease": "Ground glass nodule (GGN)", "glycan_involvement": "KIT is N-glycosylated, affecting receptor function.", "mechanism": "KIT mutations detected in ctDNA from patients with GGNs, some of which are malignant.", "protein": "KIT", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maint", "gene_name": "KIT", "glycan_count": 26, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05724UK", "G06356OH", "G28541PG", "G37399XV", "G39446WN", "G45504EY", "G59626AS", "G80920RR", "G95865ZB", "G41247ZX", "G31852PQ", "G62765YT", "G23719VF", "G53075ES", "G61256FT", "G02528FI", "G10486CT", "G10773YW", "G45395BF", "G47644PP", "G57776ZS", "G57776ZU", "G94470IW" ], "uniprot_id": "P10721" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "medium", "disease": "Ground glass nodule (GGN)", "glycan_involvement": "RET is N-glycosylated, influencing receptor trafficking.", "mechanism": "RET mutations found in ctDNA in GGN patients, indicating possible malignant transformation.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "low", "disease": "Ground glass nodule (GGN)", "glycan_involvement": "Potential O-glycosylation affects membrane localization.", "mechanism": "HRAS mutations detected in ctDNA in GGN patients, associated with malignancy.", "protein": "HRAS", "protein_enriched": { "function": "Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). ", "gene_name": "KRAS", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01116" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "low", "disease": "Ground glass nodule (GGN)", "glycan_involvement": "Potential O-glycosylation affects function.", "mechanism": "NRAS mutations detected in ctDNA in GGN patients.", "protein": "NRAS", "protein_enriched": { "function": "Ras proteins bind GDP/GTP and possess intrinsic GTPase activity", "gene_name": "NRAS", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P01111" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "high", "disease": "Parapneumonic pleural effusion", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Intrapleural urokinase is used to promote fibrinolysis and drainage in pleural infection.", "protein": "Urokinase (uPA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11477479" }, { "confidence": "high", "disease": "Parapneumonic pleural effusion", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "tPA is used for intrapleural fibrinolysis in pleural infection.", "protein": "tPA (tissue plasminogen activator)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11477479" }, { "confidence": "medium", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "N-glycosylation modulates immune checkpoint function.", "mechanism": "PD-L1 expression may guide immunotherapy in SCLC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11477479" }, { "confidence": "low", "disease": "Malignant pleural mesothelioma", "glycan_involvement": "Aberrant O-glycosylation exposes tumor antigens.", "mechanism": "MUC1 overexpression and altered glycosylation are associated with mesothelioma progression.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC11477479" }, { "confidence": "high", "disease": "Invasive Group A Streptococcal infection", "glycan_involvement": "Glycosylation of M protein enhances resistance to phagocytosis.", "mechanism": "M protein mediates immune evasion and adhesion, promoting invasive disease.", "protein": "Streptococcal M protein", "protein_enriched": { "function": "Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the ", "gene_name": "spa", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02976" }, "relationship_type": "causal", "source_pmcid": "PMC11504414" }, { "confidence": "medium", "disease": "Invasive Group A Streptococcal infection", "glycan_involvement": "Glycosylation stabilizes enzyme and modulates host interactions.", "mechanism": "C5a peptidase cleaves complement C5a, impairing neutrophil recruitment.", "protein": "Streptococcal C5a peptidase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99ZP0" }, "relationship_type": "causal", "source_pmcid": "PMC11504414" }, { "confidence": "high", "disease": "Cellulitis", "glycan_involvement": "Capsule is a glycan-rich structure critical for immune evasion.", "mechanism": "Capsule mimics host glycosaminoglycans, preventing immune recognition.", "protein": "Streptococcal hyaluronic acid capsule", "relationship_type": "causal", "source_pmcid": "PMC11504414" }, { "confidence": "high", "disease": "Bacteremia", "glycan_involvement": "Surface glycosylation impedes complement deposition.", "mechanism": "M protein facilitates bloodstream survival by resisting opsonization.", "protein": "Streptococcal M protein", "protein_enriched": { "function": "Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the ", "gene_name": "spa", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02976" }, "relationship_type": "causal", "source_pmcid": "PMC11504414" }, { "confidence": "medium", "disease": "Infective endocarditis", "glycan_involvement": "Glycan capsule is essential for colonization and persistence.", "mechanism": "Capsule enables adherence to heart valves and evasion of host defenses.", "protein": "Streptococcal hyaluronic acid capsule", "relationship_type": "causal", "source_pmcid": "PMC11504414" }, { "confidence": "high", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Ferritin is a glycoprotein; glycosylation affects its serum stability and clearance.", "mechanism": "Ferritin is markedly elevated in HLH due to macrophage activation and hyperinflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "high", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Fibrinogen glycosylation modulates its function and clearance.", "mechanism": "Low fibrinogen is a diagnostic criterion for HLH, reflecting consumption in hyperinflammatory states.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "LDH is glycosylated, which may affect its serum half-life.", "mechanism": "Elevated LDH reflects tissue damage and hemophagocytosis in HLH.", "protein": "LDH (Lactate Dehydrogenase)", "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Transferrin glycosylation affects its receptor binding and clearance.", "mechanism": "Transferrin saturation may be altered in HLH due to iron metabolism dysregulation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "high", "disease": "Dengue Fever", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "Dengue serology detects IgG as evidence of infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Highly glycosylated; glycan changes reflect inflammation.", "mechanism": "Acute phase reactant elevated in HLH.", "protein": "Alpha-1-acid glycoprotein (Orosomucoid)", "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation affects its clearance and function.", "mechanism": "May decrease due to hemolysis in HLH.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates anti-protease activity.", "mechanism": "Acute phase protein elevated in inflammation.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "low", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation affects copper binding and stability.", "mechanism": "Acute phase reactant, may be altered in HLH.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "low", "disease": "Hemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Upregulated in macrophage activation and iron metabolism dysregulation.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC11535575" }, { "confidence": "medium", "disease": "Autoimmune disease (Ro52/60 seropositivity)", "glycan_involvement": "Ro52/60 are glycoproteins; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Ro52/60 autoantibodies are markers of systemic autoimmunity; their presence may indicate immune dysregulation.", "protein": "Ro52/60 (SSA/Ro)", "relationship_type": "biomarker", "source_pmcid": "PMC11535583" }, { "confidence": "high", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "sIL-2R is a glycoprotein; glycosylation is essential for its secretion and stability.", "mechanism": "Elevated sIL-2R reflects T-cell activation and is used as a surrogate marker for HLH activity.", "protein": "Soluble interleukin-2 receptor (sIL-2R/CD25)", "relationship_type": "biomarker", "source_pmcid": "PMC11535583" }, { "confidence": "high", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "IVIG glycosylation modulates Fc receptor binding and anti-inflammatory effects.", "mechanism": "IVIG is used to modulate immune response and suppress hyperinflammation in HLH.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11535583" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "Glycosylation affects sIL-2R serum levels and detection.", "mechanism": "Used as a surrogate marker to distinguish HLH activity from liver injury in VBDS.", "protein": "Soluble interleukin-2 receptor (sIL-2R/CD25)", "relationship_type": "biomarker", "source_pmcid": "PMC11535583" }, { "confidence": "low", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may influence autoantigenicity.", "mechanism": "Ro52/60 seropositivity may indicate underlying immune dysregulation contributing to HLH.", "protein": "Ro52/60 (SSA/Ro)", "relationship_type": "biomarker", "source_pmcid": "PMC11535583" }, { "confidence": "high", "disease": "Mixed connective tissue disease (MCTD)", "glycan_involvement": "Glycosylation affects C3 stability and function in complement activation.", "mechanism": "Low C3 is indicative of disease activity and immune complex formation.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "high", "disease": "Mixed connective tissue disease (MCTD)", "glycan_involvement": "Glycosylation modulates C4 function in immune response.", "mechanism": "Low C4 is a marker of active autoimmune disease and complement consumption.", "protein": "C4", "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "high", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation influences ferritin secretion and stability.", "mechanism": "Markedly elevated ferritin is a diagnostic marker for HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "high", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation affects fibrinogen function in coagulation and inflammation.", "mechanism": "Low fibrinogen is a diagnostic criterion for HLH.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered IgG glycosylation modulates inflammatory activity.", "mechanism": "Autoantibodies (IgG) drive immune complex formation and tissue damage.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11535614" }, { "confidence": "medium", "disease": "Mixed connective tissue disease (MCTD)", "glycan_involvement": "Glycosylation impacts antibody stability and immune recognition.", "mechanism": "ANA positivity is a hallmark of MCTD diagnosis.", "protein": "ANA (Anti-Nuclear Antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "medium", "disease": "Mixed connective tissue disease (MCTD)", "glycan_involvement": "Glycosylation affects antibody-antigen interactions.", "mechanism": "Anti-RNP antibodies are specific for MCTD.", "protein": "Anti-RNP", "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "high", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "IL-1 receptor blockade (anakinra) reduces hyperinflammation in HLH.", "protein": "IL-1 Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11535614" }, { "confidence": "low", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "Elevated ALT reflects liver involvement in HLH.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "low", "disease": "Haemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "Elevated AST is a marker of hepatic inflammation in HLH.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC11535614" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Placental Growth Factor is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Reduced levels later in pregnancy predict onset of pre-eclampsia.", "protein": "Placental Growth Factor", "relationship_type": "biomarker", "source_pmcid": "PMC11535630" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "Complement proteins are glycosylated, which is important for their function and clearance.", "mechanism": "Low or low-normal complement levels are highly suggestive of LN flare.", "protein": "Complement proteins (C3/C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11535630" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Glycosylation status may affect complement activity.", "mechanism": "Normal complement levels help differentiate pre-eclampsia from LN flare.", "protein": "Complement proteins (C3/C4)", "relationship_type": "biomarker", "source_pmcid": "PMC11535630" }, { "confidence": "high", "disease": "Lupus Nephritis (LN)", "glycan_involvement": "IgG glycosylation can modulate antibody effector function and pathogenicity.", "mechanism": "High anti-dsDNA titres are highly suggestive of LN flare.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC11535630" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "IgG glycosylation may affect immune complex formation.", "mechanism": "Stable or low anti-dsDNA titres suggest pre-eclampsia rather than LN flare.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker (negative)", "source_pmcid": "PMC11535630" }, { "confidence": "high", "disease": "interferonopathies", "glycan_involvement": "Glycosylation may affect IFI27 stability and secretion.", "mechanism": "Elevated IFI27 expression reflects type I interferon pathway activation.", "protein": "IFI27", "protein_enriched": { "function": "Type I interferon-stimulated gene (ISG) that plays a critical role in antiviral and antibacterial activity (PubMed:34722780). During bacterial infection, promotes macrophage differentiation and facili", "gene_name": "IFI44L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q53G44" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535638" }, { "confidence": "high", "disease": "interferonopathies", "glycan_involvement": "Potential glycosylation modulates IFI44L function.", "mechanism": "IFI44L upregulation is a marker of interferon signature in disease.", "protein": "IFI44L", "protein_enriched": { "function": "This protein aggregates to form microtubular structures", "gene_name": "IFI44", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8TCB0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535638" }, { "confidence": "high", "disease": "SAVI", "glycan_involvement": "Glycosylation may regulate STING trafficking and signaling.", "mechanism": "Gain-of-function mutations in STING drive SAVI via chronic IFN signaling.", "protein": "STING (TMEM173)", "relationship_type": "causal", "source_pmcid": "PMC11535638" }, { "confidence": "medium", "disease": "interferonopathies", "glycan_involvement": "Glycosylation may affect IKBKG protein interactions.", "mechanism": "IKBKG mutations can cause abnormal NF-\u03baB and IFN signaling.", "protein": "IKBKG (NEMO)", "protein_enriched": { "function": "Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhi", "gene_name": "IKBKG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K9" }, "relationship_type": "causal", "source_pmcid": "PMC11535638" }, { "confidence": "medium", "disease": "interferonopathies", "glycan_involvement": "N-glycosylation critical for IL-6R function.", "mechanism": "IL-6 blockade attempted for cutaneous/vascular symptoms.", "protein": "IL-6 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11535638" }, { "confidence": "medium", "disease": "interferonopathies", "glycan_involvement": "Glycosylation may influence JAK1 localization.", "mechanism": "JAK inhibition reduces IFN-driven inflammation.", "protein": "JAK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11535638" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is N-glycosylated, affecting stability and immune function.", "mechanism": "Low C3 indicates complement consumption in active SLE.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 glycosylation modulates complement activation.", "mechanism": "Low C4 is a marker of immune complex activation in SLE.", "protein": "C4", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "ANA are glycoproteins; glycosylation affects antigenicity.", "mechanism": "High ANA titers are diagnostic for SLE.", "protein": "ANA (anti-nuclear antibodies)", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation of IgG affects pathogenicity of anti-dsDNA antibodies.", "mechanism": "Anti-dsDNA antibodies are specific for SLE and correlate with disease activity.", "protein": "dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Infective endocarditis", "glycan_involvement": "CRP glycosylation modulates its immune functions.", "mechanism": "Elevated CRP indicates acute inflammation, supporting infection diagnosis.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "medium", "disease": "Infective endocarditis", "glycan_involvement": "Procalcitonin is glycosylated, influencing its stability.", "mechanism": "High procalcitonin is a marker of bacterial infection.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Infective endocarditis", "glycan_involvement": "Bacterial glycoproteins interact with host glycans for adhesion.", "mechanism": "S. aureus glycoproteins mediate valve colonization and abscess formation.", "protein": "Staphylococcus aureus adhesins", "relationship_type": "causal", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Lupus nephritis", "glycan_involvement": "IgG Fc glycosylation modulates immune complex formation.", "mechanism": "IgG immune complexes deposit in glomeruli, causing nephritis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Lupus nephritis", "glycan_involvement": "N-glycosylation of C3 affects complement activation in kidneys.", "mechanism": "Low C3 reflects active lupus nephritis.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC11535647" }, { "confidence": "medium", "disease": "Libman-Sacks endocarditis", "glycan_involvement": "Glycosylation influences ANA immune complex formation.", "mechanism": "Autoantibodies contribute to sterile vegetations on heart valves.", "protein": "ANA (anti-nuclear antibodies)", "relationship_type": "causal", "source_pmcid": "PMC11535647" }, { "confidence": "high", "disease": "Rhabdomyolysis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is elevated in response to inflammation and muscle breakdown.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535649" }, { "confidence": "high", "disease": "Mycoplasma pneumoniae infection", "glycan_involvement": "Glycosylation modulates CRP's immune activity.", "mechanism": "CRP rises during acute infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535649" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae infection", "glycan_involvement": "IgG glycosylation affects immune response and pathogen recognition.", "mechanism": "IgG is produced in response to infection; serology previously used for diagnosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11535649" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae infection", "glycan_involvement": "IgM glycosylation influences complement activation.", "mechanism": "IgM is produced early in infection; serology previously used for diagnosis.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535649" }, { "confidence": "high", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Glycosylation regulates CRP's interaction with immune cells.", "mechanism": "CRP is elevated in bacterial pneumonia.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11535649" }, { "confidence": "high", "disease": "Invasive aspergillosis (IA)", "glycan_involvement": "Galactomannan is a polysaccharide glycan component of fungal glycoproteins.", "mechanism": "Galactomannan is released from Aspergillus cell wall during infection and detected in serum.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "high", "disease": "Invasive gastrointestinal aspergillosis (IGIA)", "glycan_involvement": "Galactomannan is a glycan antigen released during fungal invasion.", "mechanism": "Elevated serum galactomannan indicates active Aspergillus infection in GI tract.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "high", "disease": "Invasive aspergillosis (IA)", "glycan_involvement": "Beta-D-glucan is a polysaccharide glycan in fungal glycoproteins.", "mechanism": "Beta-D-glucan is a cell wall glycan released by fungi during infection.", "protein": "Beta-D-glucan", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "high", "disease": "Invasive gastrointestinal aspergillosis (IGIA)", "glycan_involvement": "Beta-D-glucan is a glycan marker of fungal invasion.", "mechanism": "Elevated serum beta-D-glucan reflects fungal cell wall breakdown in GI infection.", "protein": "Beta-D-glucan", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "medium", "disease": "Thrombotic vasculopathy", "glycan_involvement": "IgG is N-glycosylated, affecting immune complex formation.", "mechanism": "IgG deposition tested in skin biopsy for vasculopathy diagnosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "medium", "disease": "Thrombotic vasculopathy", "glycan_involvement": "C3 is glycosylated, modulating complement activation.", "mechanism": "C3 deposition tested in skin biopsy for vascular inflammation.", "protein": "Complement 3 (C3)", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "low", "disease": "Thrombotic vasculopathy", "glycan_involvement": "Albumin is glycosylated, influencing vascular permeability.", "mechanism": "Albumin tested in skin biopsy for vascular pathology.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "medium", "disease": "Thrombotic thrombocytopenic purpura", "glycan_involvement": "ADAMTS13 is glycosylated, affecting protease activity.", "mechanism": "Low ADAMTS13 activity associated with TTP.", "protein": "Von Willebrand factor-cleaving protease (ADAMTS13)", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "medium", "disease": "Thrombotic vasculopathy", "glycan_involvement": "Beta-2 glycoprotein I is glycosylated, modulating immune response.", "mechanism": "Beta-2 glycoprotein I antibody tested for vascular autoimmune disease.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Platelet factor 4 is glycosylated, influencing platelet aggregation.", "mechanism": "Platelet factor 4 antibody tested for heparin-induced thrombocytopenia.", "protein": "Platelet factor 4", "relationship_type": "biomarker", "source_pmcid": "PMC11590444" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BDNF is a glycoprotein; glycosylation may affect stability and receptor interaction.", "mechanism": "BDNF deficiency in hippocampus/entorhinal cortex leads to neurodegeneration; BDNF delivery promotes neuroregeneration and improves cognitive function.", "protein": "BDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "NGF is glycosylated; glycosylation may affect maturation and receptor binding.", "mechanism": "Impaired processing of pro-NGF to mature NGF leads to cholinergic neuron atrophy; NGF delivery improves memory but may cause pain.", "protein": "NGF", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect BDNF stability and transport.", "mechanism": "BDNF protects dopaminergic neurons and induces dopamine secretion; BDNF delivery prevents neuronal death.", "protein": "BDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may influence NGF receptor interactions.", "mechanism": "NGF deprivation affects oligodendrocyte differentiation and myelination; NGF may promote remyelination but can also induce oligodendrocyte death via p75NTR.", "protein": "NGF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "BDNF glycosylation may affect its distribution and activity.", "mechanism": "BDNF delivery promotes neuroregeneration, improves motor function, and increases myelination in MS models.", "protein": "BDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect NGF targeting and activity.", "mechanism": "NGF administration may affect non-dopaminergic neurons; limited efficacy due to lack of TrkA in substantia nigra.", "protein": "NGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect BDNF stability and BBB penetration.", "mechanism": "Lower BDNF levels in stroke patients; BDNF delivery promotes recovery and neurogenesis.", "protein": "BDNF", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Rabies virus glycoprotein used for exosome targeting; NGF glycosylation may affect function.", "mechanism": "NGF mRNA delivered via exosomes promotes neurogenesis and prevents cell death in ischemic brain injury.", "protein": "NGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is glycosylated; glycosylation may affect processing and aggregation.", "mechanism": "APP cleavage by \u03b2- and \u03b3-secretases produces amyloid-\u03b2 peptides, leading to plaque formation and neurotoxicity.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation may affect aggregation and toxicity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, leading to neuronal death; tau aggregates spread pathology.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11595909" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Apo(a) is heavily glycosylated, affecting its size, plasma levels, and interactions.", "mechanism": "Elevated Lp(a) is an independent risk factor for CVD; promotes atherogenesis and thrombosis.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11595969" }, { "confidence": "high", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Glycosylation of apo(a) modulates Lp(a) structure and function.", "mechanism": "High Lp(a) levels are associated with increased risk of CHD.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11595969" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences apo(a) interactions with vascular components.", "mechanism": "Lp(a) carries oxidized phospholipids, mediates monocyte adhesion, and inhibits fibrinolysis, promoting plaque formation.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11595969" }, { "confidence": "medium", "disease": "Familial hypercholesterolemia", "glycan_involvement": "Apo(a) glycosylation polymorphism affects Lp(a) levels.", "mechanism": "Individuals with familial hypercholesterolemia often have elevated Lp(a), compounding CVD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11595969" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may affect Lp(a) clearance and response to therapies.", "mechanism": "Lowering Lp(a) via diet, drugs, or apheresis reduces CVD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11595969" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of apo(a) modulates binding to fibrinogen.", "mechanism": "Lp(a) inhibits fibrinolysis by competing with plasminogen, increasing thrombosis risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11595969" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Diet may indirectly affect glycosylation and Lp(a) secretion.", "mechanism": "Dietary saturated fats increase Lp(a) levels, raising CVD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11595969" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Possible modulation of glycosylation and hepatic secretion.", "mechanism": "Diets rich in unsaturated fats (MUFA/PUFA) may lower Lp(a) and reduce CVD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11595969" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation state may change during inflammation.", "mechanism": "Lp(a) acts as an acute-phase protein, increasing during inflammation and contributing to plaque formation.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11595969" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Lifestyle may influence glycosylation and Lp(a) metabolism.", "mechanism": "Physical activity and weight management can lower Lp(a) and CVD risk.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11595969" }, { "confidence": "high", "disease": "Acute cholecystitis", "glycan_involvement": "N-glycosylation affects CRP stability and serum half-life.", "mechanism": "CRP levels rise in response to inflammation in cholecystitis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "high", "disease": "Obstructive jaundice", "glycan_involvement": "N-glycosylation required for ALP secretion and activity.", "mechanism": "Elevated ALP indicates biliary obstruction.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "high", "disease": "Obstructive jaundice", "glycan_involvement": "N-glycosylation modulates GGT membrane localization.", "mechanism": "GGT elevation reflects cholestasis and biliary injury.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "medium", "disease": "Hepatocytolysis syndrome", "glycan_involvement": "Glycosylation influences AST serum stability.", "mechanism": "AST release signals hepatocyte injury.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "medium", "disease": "Hepatocytolysis syndrome", "glycan_involvement": "Glycosylation affects ALT folding and secretion.", "mechanism": "ALT elevation marks liver cell damage.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates CRP immune interactions.", "mechanism": "CRP increases during systemic infection.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "medium", "disease": "Pregnancy complication (thrombosis prevention)", "glycan_involvement": "Antithrombin glycosylation required for enoxaparin binding.", "mechanism": "Enoxaparin enhances antithrombin activity to prevent thrombosis.", "protein": "Enoxaparin (antithrombin-binding)", "relationship_type": "therapeutic target", "source_pmcid": "PMC11595974" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Fc glycosylation regulates IgG effector functions.", "mechanism": "IgG mediates immune defense against infection.", "protein": "Immunoglobulin G", "relationship_type": "protective", "source_pmcid": "PMC11595974" }, { "confidence": "low", "disease": "Obstructive jaundice", "glycan_involvement": "N-glycosylation patterns change in hepatic disease.", "mechanism": "Altered transferrin glycoforms may indicate liver dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "low", "disease": "Hepatocytolysis syndrome", "glycan_involvement": "Glycosylation required for ceruloplasmin stability.", "mechanism": "Ceruloplasmin levels reflect hepatic synthetic function.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11595974" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "N-glycosylation modulates CYP2D6 expression and activity.", "mechanism": "CYP2D6 overexpression increases pro-inflammatory cytokines and hepatic oxidative stress.", "protein": "CYP2D6", "protein_enriched": { "function": "", "gene_name": "10A19I.15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV1" }, "relationship_type": "causal", "source_pmcid": "PMC11596063" }, { "confidence": "high", "disease": "Energy metabolism disorder", "glycan_involvement": "N-glycosylation stabilizes GSTZ1, affecting antioxidative capacity.", "mechanism": "GSTZ1 depletion leads to oxidative stress and energy metabolism disorder in liver.", "protein": "GSTZ1", "protein_enriched": { "function": "", "gene_name": "10A19I.13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV3" }, "relationship_type": "causal", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Liver oxidative stress", "glycan_involvement": "N-glycosylation regulates HSP90B1 stability and stress response.", "mechanism": "HSP90B1 expression correlates with ROS-induced oxidative stress in liver.", "protein": "HSP90B1", "protein_enriched": { "function": "Involved in synthesis of starch. Catalyzes the synthesis of ADP-glucose, a molecule that serves as an activated glycosyl donor for alpha-1,4-glucan synthesis. Essential for starch synthesis in leaf ch", "gene_name": "AGPL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q688T8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation affects GLUD1 function in redox regulation.", "mechanism": "GLUD1 inhibits progression by regulating ROS and oxidative stress in mitochondria.", "protein": "GLUD1", "protein_enriched": { "function": "", "gene_name": "10A19I.10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV6" }, "relationship_type": "protective", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Hepatobiliary injury (sickle cell disease)", "glycan_involvement": "N-glycosylation modulates CD163-mediated protection.", "mechanism": "CD163 prevents injury by inhibiting oxidative stress, inflammation, and thrombosis.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "protective", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Peroxisomal dysfunction", "glycan_involvement": "N-glycosylation is critical for PEX14 function.", "mechanism": "Reduced PEX14 impairs peroxisomes, causing liver oxidative stress.", "protein": "PEX14", "protein_enriched": { "function": "", "gene_name": "10A19I.8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV8" }, "relationship_type": "causal", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Drug-induced liver injury", "glycan_involvement": "N-glycosylation modulates CYP1A2 activity.", "mechanism": "CYP1A2 upregulation during drug metabolism indicates oxidative stress.", "protein": "CYP1A2", "protein_enriched": { "function": "", "gene_name": "10A19I.14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV2" }, "relationship_type": "biomarker", "source_pmcid": "PMC11596063" }, { "confidence": "low", "disease": "Liver oxidative stress", "glycan_involvement": "N-glycosylation affects F5 function in oxidation.", "mechanism": "F5 (coagulation factor V) is linked to multicopper oxidase activity in oxidative pathways.", "protein": "F5", "protein_enriched": { "function": "", "gene_name": "10A19I.7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV9" }, "relationship_type": "biomarker", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Apoptosis (liver)", "glycan_involvement": "N-glycosylation modulates HSPA8 stress response.", "mechanism": "HSPA8 upregulation alleviates cytochrome c-mediated apoptosis under oxidative stress.", "protein": "HSPA8", "protein_enriched": { "function": "", "gene_name": "10A19I.11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV5" }, "relationship_type": "protective", "source_pmcid": "PMC11596063" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "N-glycosylation stabilizes GSTZ1, enhancing antioxidant function.", "mechanism": "GSTZ1 regulates hepatic fatty acid oxidation and lipid metabolism.", "protein": "GSTZ1", "protein_enriched": { "function": "", "gene_name": "10A19I.13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV3" }, "relationship_type": "protective", "source_pmcid": "PMC11596063" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "PrP is a glycoprotein; glycosylation affects folding and aggregation.", "mechanism": "Misfolding and aggregation of PrP leads to neurodegeneration.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC11610568" }, { "confidence": "high", "disease": "Chronic Wasting Disease (CWD)", "glycan_involvement": "Glycosylation modulates strain properties and transmission.", "mechanism": "Misfolded PrP accumulates and propagates in cervids, causing CWD.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC11610568" }, { "confidence": "medium", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Increased STX6 expression enhances susceptibility to prion infection.", "protein": "Syntaxin-6 (STX6)", "protein_enriched": { "function": "SNARE promoting movement of transport vesicles to target membranes. Targets endosomes to the trans-Golgi network, and may therefore function in retrograde trafficking. Together with SNARE STX12, promo", "gene_name": "STX6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43752" }, "relationship_type": "risk modifier", "source_pmcid": "PMC11610568" }, { "confidence": "high", "disease": "Genetic CJD (V180I)", "glycan_involvement": "Mutation may affect glycosylation sites and disease phenotype.", "mechanism": "V180I mutation in PrP gene alters protein structure, leading to disease.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC11610568" }, { "confidence": "medium", "disease": "Renal tubular injury", "glycan_involvement": "PrP glycosylation may affect secretion and detection.", "mechanism": "Urinary PrP is elevated in patients with renal tubular injury.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "biomarker", "source_pmcid": "PMC11610568" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "Glycosylation may influence urinary PrP levels.", "mechanism": "Urinary PrP levels can help distinguish tubular injury from MCD.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "biomarker", "source_pmcid": "PMC11610568" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "Glycosylation may affect antibody binding and clearance.", "mechanism": "Lowering PrP levels (ASOs, small molecules, antibodies) is neuroprotective.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC11610568" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may modulate PrP-A\u03b2 interactions.", "mechanism": "Abnormal PrP deposition observed with A\u03b2 in vPSPr cases.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "co-pathology", "source_pmcid": "PMC11610568" }, { "confidence": "high", "disease": "Yeast prionopathy ([PSI+])", "glycan_involvement": "Not applicable (yeast protein, not glycosylated).", "mechanism": "Aggregation of Sup35p forms infectious [PSI+] prion state.", "protein": "Sup35p", "protein_enriched": { "function": "GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA (PubMed:34413231, PubMed:7556078).", "gene_name": "SUP35", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05453" }, "relationship_type": "causal", "source_pmcid": "PMC11610568" }, { "confidence": "medium", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "PrP levels in blood and CSF can monitor disease and therapeutic response.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "biomarker", "source_pmcid": "PMC11610568" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CD147 is a highly glycosylated protein; glycosylation modulates its function and EV incorporation.", "mechanism": "EVs from chemotherapy-treated CRC cells show increased CD147, promoting glycolysis and cancer progression.", "protein": "CD147", "protein_enriched": { "function": "Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photor", "gene_name": "BSG", "glycan_count": 62, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G49108TO", "G01160VV", "G02815KT", "G05049YU", "G08918WF", "G10488MI", "G15127JD", "G15664MX", "G23719VF", "G27058EU", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G43223CG", "G45395BF", "G50856PC", "G53075ES", "G57776ZS", "G59626AS", "G62765YT", "G65414LI", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G74381CZ", "G77330BQ", "G79666IR", "G80075MS", "G80920RR", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G29068FM", "G43417UB", "G05724UK", "G05962QB", "G08290VR", "G11870QZ", "G13131HA", "G20210JR", "G20528HD", "G23294PN", "G28681TP", "G32788FZ", "G35541EV", "G46275YY", "G47644PP", "G49755GI", "G60967DT", "G64527OM", "G70101JE", "G70619PT", "G80479JV", "G83460ZZ", "G85269DF", "G92062TF", "G93718GY", "G50713DU" ], "uniprot_id": "P35613" }, "relationship_type": "biomarker", "source_pmcid": "PMC11651120" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "VEGF glycosylation affects its stability and receptor binding.", "mechanism": "EVs from CRC cells post-chemotherapy are enriched in VEGF, supporting angiogenesis and tumor growth.", "protein": "VEGF", "relationship_type": "biomarker", "source_pmcid": "PMC11651120" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may regulate \u03b2-catenin stability and signaling.", "mechanism": "EVs from CRC cells post-chemotherapy show increased \u03b2-catenin, linked to cancer progression.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "biomarker", "source_pmcid": "PMC11651120" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "HLA-DR is N-glycosylated; glycosylation affects antigen presentation and immune modulation.", "mechanism": "EVs from MHC class II-expressing melanoma cells have increased HLA-DR, promoting immune escape and metastasis.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "causal", "source_pmcid": "PMC11651120" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "PDL1 glycosylation is critical for its stability and immune inhibitory function.", "mechanism": "EVs from melanoma cells express PDL1, inhibiting immune response and facilitating progression.", "protein": "PDL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11651120" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia", "glycan_involvement": "Syndecan is a proteoglycan; glycosylation (heparan sulfate chains) mediates EV sorting.", "mechanism": "MSC-EVs regulate inflammatory EV release via Syndecan-Syntenin-Alix, counteracting fibrosis and oxidative stress.", "protein": "Syndecan-Syntenin-Alix complex", "relationship_type": "protective", "source_pmcid": "PMC11651120" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "PKM2 glycosylation may affect its enzymatic activity and EV packaging.", "mechanism": "EVs from CRC cells post-chemotherapy are enriched in PKM2, indicating metabolic reprogramming.", "protein": "PKM2", "protein_enriched": { "function": "Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:2084", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618" }, "relationship_type": "biomarker", "source_pmcid": "PMC11651120" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Tetraspanins are glycoproteins; glycosylation may affect EV incorporation and biomarker utility.", "mechanism": "EV tetraspanin levels decrease after bariatric surgery, reflecting improved cardiovascular/metabolic profile.", "protein": "CD9/CD63/CD81", "relationship_type": "biomarker", "source_pmcid": "PMC11651120" }, { "confidence": "medium", "disease": "Renal disease", "glycan_involvement": "CD47 glycosylation modulates immune evasion and targeting efficiency.", "mechanism": "Engineered RBC-EVs expressing CD47 and loaded with therapeutic cargo target injured renal cells.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11651120" }, { "confidence": "high", "disease": "Melanoma (immune modulation)", "glycan_involvement": "Direct involvement; high mannose glycosylation on sEV surface is key for receptor-mediated uptake.", "mechanism": "High mannose glycans on sEVs mediate uptake by dendritic cells via mannose receptor, influencing immune response.", "protein": "High mannose glycans (on sEVs)", "relationship_type": "causal", "source_pmcid": "PMC11651120" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Lu/BCAM is a glycoprotein; glycosylation modulates its adhesive properties.", "mechanism": "Activated Lu/BCAM on sickle RBCs mediates adhesion to endothelium and neutrophil activation, contributing to vaso-occlusion.", "protein": "Lu/BCAM", "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "ICAM4 is a glycoprotein; glycosylation affects its cell-cell interaction.", "mechanism": "ICAM4 activation on sickle RBCs promotes adhesion to endothelium and neutrophil activation, facilitating vaso-occlusion.", "protein": "ICAM4", "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "CD44 is heavily glycosylated; glycosylation regulates ligand binding and adhesion.", "mechanism": "Upregulated CD44 on sickle RBCs enhances adhesion to endothelium, contributing to vaso-occlusion.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Neutrophil activation in SCD", "glycan_involvement": "MMP9 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Elevated plasma MMP9 reflects neutrophil degranulation and activation in SCD, associated with vaso-occlusion.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Vaso-occlusive crisis (VOC)", "glycan_involvement": "Glycosylation of Lu/BCAM modulates adhesion strength.", "mechanism": "Lu/BCAM-mediated RBC adhesion triggers neutrophil activation and VOC.", "protein": "Lu/BCAM", "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Vaso-occlusive crisis (VOC)", "glycan_involvement": "Glycosylation of ICAM4 influences adhesive interactions.", "mechanism": "ICAM4 on RBCs promotes neutrophil adhesion and VOC.", "protein": "ICAM4", "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "medium", "disease": "Vaso-occlusive crisis (VOC)", "glycan_involvement": "Glycosylation of CD44 regulates its binding to hyaluronan and endothelium.", "mechanism": "CD44-mediated RBC adhesion contributes to VOC pathogenesis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Vaso-occlusive crisis (VOC)", "glycan_involvement": "Glycosylation affects MMP9 stability and activity.", "mechanism": "MMP9 release from neutrophils is increased during VOCs.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "\u03b2-thalassemia", "glycan_involvement": "CD34 is a glycoprotein; glycosylation is important for stem cell homing.", "mechanism": "CD34+ hematopoietic stem cells are gene-edited to treat \u03b2-thalassemia.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Glycosylation of CD34 affects cell migration and engraftment.", "mechanism": "CD34+ stem cells are gene-edited to reactivate HbF for SCD therapy.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664321" }, { "confidence": "high", "disease": "Alpha thalassemia", "glycan_involvement": "Globin glycosylation may affect stability and function.", "mechanism": "De-repression of zeta globin can substitute for alpha globin, ameliorating alpha thalassemia symptoms.", "protein": "Zeta globin", "protein_enriched": { "function": "The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin", "gene_name": "HBZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02008" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664322" }, { "confidence": "high", "disease": "Sickle cell disease", "glycan_involvement": "Glycosylation may modulate BCL11A stability and DNA binding.", "mechanism": "BCL11A represses fetal globin; gene editing to reduce BCL11A increases HbF, reducing SCD severity.", "protein": "BCL11A", "protein_enriched": { "function": "Transcription factor (PubMed:16704730, PubMed:29606353). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491, PubMed:39607926). Binds to the 5'-TGACCA-3' sequence motif in re", "gene_name": "BCL11A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H165" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664322" }, { "confidence": "medium", "disease": "Barts hydrops fetalis syndrome", "glycan_involvement": "Glycosylation may affect KLF1 nuclear localization.", "mechanism": "KLF1 mutations increase embryonic globin (including zeta globin) expression, modifying disease severity.", "protein": "KLF1", "protein_enriched": { "function": "Orphan receptor. May play a role in brain function", "gene_name": "GPR45", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9Y5Y3" }, "relationship_type": "causal", "source_pmcid": "PMC11664322" }, { "confidence": "high", "disease": "Sickle cell disease", "glycan_involvement": "Glycosylation may impact HbF stability and lifespan.", "mechanism": "High HbF levels prevent HbS polymerization, reducing hemolysis and vaso-occlusive crises.", "protein": "Hemoglobin F (HbF)", "protein_enriched": { "function": "Gamma chains make up the fetal hemoglobin F, in combination with alpha chains", "gene_name": "HBG1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69891" }, "relationship_type": "protective", "source_pmcid": "PMC11664322" }, { "confidence": "medium", "disease": "Sickle cell disease", "glycan_involvement": "Glycosylation may regulate EED complex formation.", "mechanism": "Inhibition of EED by pociredir induces HbF, reducing SCD pathology.", "protein": "Embryonic Ectoderm Development (EED)", "protein_enriched": { "function": "Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recog", "gene_name": "EED", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92275SC" ], "uniprot_id": "O75530" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664322" }, { "confidence": "medium", "disease": "Sickle cell disease", "glycan_involvement": "Laminin glycosylation is critical for cell adhesion properties.", "mechanism": "RBC adhesion to laminin is increased in SCD, contributing to vaso-occlusion.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11664322" }, { "confidence": "medium", "disease": "Vaso-occlusive events", "glycan_involvement": "Glycosylation may affect TNFAIP3 secretion and activity.", "mechanism": "Upregulation after hydroxyurea treatment reduces inflammation during VOE.", "protein": "TNFAIP3", "protein_enriched": { "function": "Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pat", "gene_name": "TNFAIP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21580" }, "relationship_type": "protective", "source_pmcid": "PMC11664322" }, { "confidence": "medium", "disease": "Vaso-occlusive events", "glycan_involvement": "Cell surface glycosylation modulates receptor function.", "mechanism": "Upregulation after hydroxyurea treatment mediates anti-inflammatory effects.", "protein": "ADORA2A", "relationship_type": "protective", "source_pmcid": "PMC11664322" }, { "confidence": "high", "disease": "Beta thalassemia", "glycan_involvement": "Therapeutic glycoprotein; glycosylation affects pharmacokinetics.", "mechanism": "Luspatercept improves anemia and enables transfusion independence in \u03b2-thalassemia.", "protein": "Luspatercept", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664322" }, { "confidence": "high", "disease": "Beta thalassemia", "glycan_involvement": "Glycosylation may affect BCL11A function.", "mechanism": "CRISPR-Cas9 editing of BCL11A enhancer reactivates HbF, enabling transfusion independence.", "protein": "BCL11A", "protein_enriched": { "function": "Transcription factor (PubMed:16704730, PubMed:29606353). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491, PubMed:39607926). Binds to the 5'-TGACCA-3' sequence motif in re", "gene_name": "BCL11A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H165" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11664322" }, { "confidence": "high", "disease": "IgG4-related disease (IgG4-RD)", "glycan_involvement": "IgG4 is a glycoprotein; glycosylation affects its structure and immune function.", "mechanism": "Elevated serum IgG4 and tissue infiltration by IgG4+ plasma cells are diagnostic hallmarks.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC11683312" }, { "confidence": "high", "disease": "IgG4-related hepatitis", "glycan_involvement": "Glycosylation of IgG4 may modulate immune responses and tissue deposition.", "mechanism": "IgG4+ plasma cell infiltration in liver tissue leads to hepatocellular injury and fibrosis.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11683312" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may influence IgG4's interaction with immune cells and fibrotic pathways.", "mechanism": "IgG4+ plasma cells promote fibrosis via cytokine secretion (TGF-\u03b2, IL-1\u03b2, IFN-\u03b3).", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "causal", "source_pmcid": "PMC11683312" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Glycosylation status not directly discussed for differential diagnosis.", "mechanism": "IgG4 elevation helps distinguish IgG4-RD from classic AIH; AIH scoring excludes IgG4-AIH in this case.", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "differential biomarker", "source_pmcid": "PMC11683312" }, { "confidence": "high", "disease": "Diabetic Foot Infection", "glycan_involvement": "CD177 is a glycosylated cell surface protein; glycosylation is essential for its cell surface localization and immune function.", "mechanism": "Upregulated CD177 reflects neutrophil proliferation and intensified immune response during active infection.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "high", "disease": "Foot and Ankle Infection", "glycan_involvement": "Glycosylation required for CD177 function and detection.", "mechanism": "Elevated CD177 in PBMC and serum indicates active infection and neutrophil activation.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "medium", "disease": "Septic Arthritis of the Ankle", "glycan_involvement": "Glycosylation mediates cell surface expression.", "mechanism": "Increased CD177 expression correlates with neutrophil-driven inflammation in septic arthritis.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "medium", "disease": "Infected Total Ankle Replacement", "glycan_involvement": "Glycosylation is necessary for immune recognition.", "mechanism": "High CD177 levels reflect neutrophil response to prosthetic joint infection.", "protein": "CD177", "protein_enriched": { "function": "In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (PubMed:21193407). In ", "gene_name": "CD177", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8N6Q3" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "high", "disease": "Diabetic Foot Infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Upregulated RRM2 in PBMC and serum indicates immune activation and macrophage stimulation during infection.", "protein": "RRM2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49994" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "high", "disease": "Foot and Ankle Infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Elevated RRM2 levels in PBMC and serum are associated with active infection.", "protein": "RRM2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49994" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "medium", "disease": "Diabetic Foot Infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "MYBL2 upregulation in PBMC activates RRM2 transcription, reflecting immune response.", "protein": "MYBL2", "protein_enriched": { "function": "Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene", "gene_name": "MYBL2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "medium", "disease": "Foot and Ankle Infection", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Increased MYBL2 in PBMC is linked to immune activation.", "protein": "MYBL2", "protein_enriched": { "function": "Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene", "gene_name": "MYBL2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10244" }, "relationship_type": "biomarker", "source_pmcid": "PMC11686643" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates HGF stability and receptor binding.", "mechanism": "Elevated HGF reflects vascular injury and remodeling.", "protein": "HGF", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01543ZX", "G11629QQ", "G17689DH", "G22310AV", "G48414YA", "G52126RR", "G52527GH", "G57789QC", "G60542VK", "G64394MX", "G74239ZQ", "G77252PU", "G89664KV", "G93656SY", "G45637XA", "G81006GJ", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G40834TG", "G41071NU", "G42124LM", "G45395BF", "G86880BF", "G90659AW", "G41247ZX", "G46691LC", "G62765YT", "G80920RR", "G83460ZZ" ], "uniprot_id": "P14210" }, "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "high", "disease": "Inflammatory disease", "glycan_involvement": "N-glycosylation affects IL-6 secretion and receptor interaction.", "mechanism": "IL-6 is a key mediator of systemic inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Inflammatory disease", "glycan_involvement": "N-glycosylation required for OSM secretion.", "mechanism": "OSM promotes inflammatory signaling and tissue remodeling.", "protein": "OSM", "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "N-glycosylation critical for receptor function.", "mechanism": "IL-10RB is essential for anti-inflammatory signaling.", "protein": "IL-10RB", "protein_enriched": { "function": "Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 an", "gene_name": "IL10RB", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q08334" }, "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates cell-cell interactions.", "mechanism": "CNTN1 involved in cell adhesion and vascular integrity.", "protein": "CNTN1", "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects IGFBP3 stability.", "mechanism": "IGFBP3 regulates IGF signaling in vascular tissues.", "protein": "IGFBP3", "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "O-glycosylation required for secretion.", "mechanism": "FGF23 modulates phosphate metabolism and vascular calcification.", "protein": "FGF23", "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation influences ligand binding.", "mechanism": "sRAGE acts as a decoy receptor for advanced glycation end-products.", "protein": "sRAGE", "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "high", "disease": "Inflammatory disease", "glycan_involvement": "N-glycosylation required for CRP secretion.", "mechanism": "CRP is an acute phase reactant elevated in inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "MMP9 degrades extracellular matrix, contributing to vascular remodeling.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC11692311" }, { "confidence": "high", "disease": "Familial Frontotemporal Dementia (fFTD)", "glycan_involvement": "PGRN is a glycoprotein; glycosylation is required for its secretion and stability.", "mechanism": "GRN haploinsufficiency leads to reduced PGRN levels, causing neuronal degeneration in the frontal lobe.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "causal", "source_pmcid": "PMC11713588" }, { "confidence": "high", "disease": "Frontotemporal Dementia (FTD)", "glycan_involvement": "Glycosylation affects PGRN trafficking and extracellular levels.", "mechanism": "Reduced PGRN levels are associated with neurodegeneration in FTD.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "causal", "source_pmcid": "PMC11713588" }, { "confidence": "medium", "disease": "Familial Frontotemporal Dementia (fFTD)", "glycan_involvement": "Sortilin is a glycoprotein; glycosylation may affect ligand binding and trafficking.", "mechanism": "Sortilin mediates endocytosis and lysosomal degradation of PGRN; blocking Sortilin increases extracellular PGRN.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713588" }, { "confidence": "medium", "disease": "Other dementias", "glycan_involvement": "Glycosylation status may influence detection and function.", "mechanism": "Altered PGRN levels may indicate neurodegenerative processes.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "biomarker", "source_pmcid": "PMC11713588" }, { "confidence": "medium", "disease": "Frontotemporal Dementia (FTD)", "glycan_involvement": "Glycosylation may modulate Sortilin's receptor function.", "mechanism": "Inhibition of Sortilin-mediated PGRN endocytosis increases PGRN availability.", "protein": "Sortilin (SORT1)", "protein_enriched": { "function": "Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is ", "gene_name": "SORT1", "glycan_count": 71, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G05049YU", "G08918WF", "G10773YW", "G11870QZ", "G14972EH", "G14994KB", "G16175ZV", "G23294PN", "G23984SE", "G25418HZ", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47448YK", "G48414YA", "G57776ZS", "G60177UT", "G68490OW", "G70232NH", "G70441OD", "G75983OB", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G96577RX", "G22310AV", "G47012YE", "G92062TF", "G01650EU", "G05528SJ", "G15664MX", "G20210JR", "G22573RC", "G22768VO", "G25079LO", "G31852PQ", "G43769HG", "G49642SA", "G51653BI", "G54010QB", "G58087IP", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G83460ZZ", "G07246CJ", "G11629QQ", "G29299MO", "G62894KT", "G71146HJ", "G77582RK", "G93718GY", "G98611JV", "G49108TO" ], "uniprot_id": "Q99523" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11713588" }, { "confidence": "high", "disease": "White Matter Hyperintensities (WMH)", "glycan_involvement": "N-glycosylation affects protein stability and myelin sheath interactions.", "mechanism": "Associated with elevated WMH volume, reflecting myelin integrity.", "protein": "Oligodendrocyte Myelin Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "high", "disease": "White Matter Hyperintensities (WMH)", "glycan_involvement": "N-glycosylation modulates receptor trafficking and synaptic localization.", "mechanism": "Associated with synaptic function and WMH burden.", "protein": "Neuronal Pentraxin Receptor", "protein_enriched": { "function": "Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths", "gene_name": "PDSS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5T2R2" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "Glycosylation influences neuroinflammatory signaling.", "mechanism": "Predicts incident dementia risk via WMH association.", "protein": "Oligodendrocyte Myelin Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "Glycosylation affects receptor function in neurodegeneration.", "mechanism": "Plasma levels predict dementia risk.", "protein": "Neuronal Pentraxin Receptor", "protein_enriched": { "function": "Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths", "gene_name": "PDSS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5T2R2" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "Lacunar Infarcts", "glycan_involvement": "GPI-anchor and glycosylation modulate cell adhesion.", "mechanism": "Associated with axonal integrity and infarct risk.", "protein": "Contactin-2", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "Cerebral Small Vessel Disease (cSVD)", "glycan_involvement": "N-glycosylation regulates cell-cell adhesion.", "mechanism": "Reflects endothelial integrity and vessel permeability.", "protein": "Cadherin-5 (VE-cadherin)", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "Cerebral Microhemorrhages (CMH)", "glycan_involvement": "N-glycosylation affects secretion and receptor binding.", "mechanism": "Involved in angiogenesis and vascular remodeling.", "protein": "Angiopoietin-2", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "White Matter Hyperintensities (WMH)", "glycan_involvement": "N-glycosylation modulates synaptic specificity.", "mechanism": "Synaptic adhesion molecule linked to WMH volume.", "protein": "Neurexin-1", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "Lacunar Infarcts", "glycan_involvement": "N-glycosylation influences axon-glia interactions.", "mechanism": "Associated with axonal stability and infarct risk.", "protein": "Neurofascin", "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "N-glycosylation modulates cell adhesion and migration.", "mechanism": "Linked to neurodegeneration and cognitive decline.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC11715001" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Insulin is glycosylated, affecting its stability and receptor binding.", "mechanism": "Insulin deficiency is causal in T1DM; exogenous insulin is required for glycemic control.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11771437" }, { "confidence": "medium", "disease": "Liver Enlargement due to Glycogen Deposition", "glycan_involvement": "Insulin glycosylation may modulate its activity and hepatic effects.", "mechanism": "Poor glycemic control and fluctuating insulin levels lead to excessive hepatic glycogen storage.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11771437" }, { "confidence": "medium", "disease": "Delayed Puberty", "glycan_involvement": "FSH is heavily glycosylated; glycosylation affects its bioactivity and half-life.", "mechanism": "Altered FSH levels indicate hypogonadotropic hypogonadism contributing to delayed puberty.", "protein": "FSH", "relationship_type": "biomarker", "source_pmcid": "PMC11771437" }, { "confidence": "medium", "disease": "Delayed Puberty", "glycan_involvement": "LH glycosylation modulates receptor interaction and hormone clearance.", "mechanism": "Altered LH levels reflect impaired gonadal axis function in delayed puberty.", "protein": "LH", "relationship_type": "biomarker", "source_pmcid": "PMC11771437" }, { "confidence": "low", "disease": "Liver Enlargement due to Glycogen Deposition", "glycan_involvement": "ALT is glycosylated, which may affect its secretion and stability.", "mechanism": "Elevated ALT indicates hepatocellular injury due to glycogen overload.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11771437" }, { "confidence": "low", "disease": "Liver Enlargement due to Glycogen Deposition", "glycan_involvement": "AST glycosylation may influence its serum levels.", "mechanism": "Elevated AST reflects liver injury associated with glycogen deposition.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11771437" }, { "confidence": "medium", "disease": "Growth Failure", "glycan_involvement": "Glycosylation of insulin affects its bioactivity and metabolic effects.", "mechanism": "Insulin deficiency impairs anabolic processes and growth.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11771437" }, { "confidence": "low", "disease": "Growth Failure", "glycan_involvement": "FSH glycosylation impacts its endocrine function.", "mechanism": "Low FSH may contribute to impaired growth via reduced sex steroid production.", "protein": "FSH", "relationship_type": "biomarker", "source_pmcid": "PMC11771437" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "Insulin glycosylation may affect lipid metabolism.", "mechanism": "Insulin deficiency leads to increased lipolysis and elevated triglycerides.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11771437" }, { "confidence": "low", "disease": "Delayed Puberty", "glycan_involvement": "Glycosylation state of FSH determines its therapeutic efficacy.", "mechanism": "FSH supplementation may be considered to induce puberty.", "protein": "FSH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11771437" }, { "confidence": "high", "disease": "Hereditary Diffuse Gastric Cancer (HDGC)", "glycan_involvement": "CDH1 is a glycoprotein; glycosylation affects cell adhesion and tumor suppression.", "mechanism": "Germline inactivation or regulatory region CNVs cause loss of E-cadherin function, promoting diffuse gastric cancer.", "protein": "CDH1", "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Hereditary Diffuse Gastric Cancer (HDGC)", "glycan_involvement": "CTNNA1 is glycosylated; glycosylation may modulate adhesion.", "mechanism": "Germline variants disrupt cell adhesion, contributing to HDGC.", "protein": "CTNNA1", "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Lynch syndrome / gastric cancer", "glycan_involvement": "MLH1 is glycosylated; glycosylation may affect stability/function.", "mechanism": "Deletion in MLH1 regulatory region predisposes to gastric cancer.", "protein": "MLH1", "protein_enriched": { "function": "Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t", "gene_name": "MLH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P40692" }, "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Hereditary Diffuse Gastric Cancer (HDGC)", "glycan_involvement": "CDH3 is a glycoprotein; glycosylation affects adhesion.", "mechanism": "CNV deletion in CDH3 regulatory region downregulates CDH1, promoting HDGC.", "protein": "CDH3", "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "high", "disease": "Mucopolysaccharidoses type III", "glycan_involvement": "XYLT1 initiates glycosaminoglycan (GAG) chain synthesis on proteoglycans.", "mechanism": "Targeting XYLT1 with ASOs/siRNAs reduces GAG biosynthesis and substrate accumulation.", "protein": "XYLT1", "protein_enriched": { "function": "Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN. Transfers D-xylose from UDP-D-xylose to specific serine residues of the core protei", "gene_name": "XYLT1", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB" ], "uniprot_id": "Q86Y38" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11771725" }, { "confidence": "high", "disease": "Fabry disease", "glycan_involvement": "GLA is a glycoprotein; glycosylation affects lysosomal targeting and activity.", "mechanism": "Pathogenic variants in GLA cause deficient alpha-galactosidase A, leading to glycosphingolipid accumulation.", "protein": "GLA", "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Hereditary transthyretin amyloidosis", "glycan_involvement": "TTR is glycosylated; glycosylation may affect aggregation propensity.", "mechanism": "Pathogenic TTR variants cause amyloid deposition.", "protein": "TTR", "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "high", "disease": "Familial hypercholesterolemia", "glycan_involvement": "LDLR glycosylation is essential for receptor function and trafficking.", "mechanism": "Pathogenic LDLR variants impair LDL uptake, causing hypercholesterolemia.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "BRCA2 is glycosylated; glycosylation may affect protein stability.", "mechanism": "Pathogenic variants increase breast cancer risk.", "protein": "BRCA2", "protein_enriched": { "function": "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by ", "gene_name": "BRCA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G03238UC", "G37399XV", "G41247ZX", "G90382BL", "G49108TO" ], "uniprot_id": "P51587" }, "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "medium", "disease": "Breast cancer / Hereditary gastric cancer", "glycan_involvement": "PALB2 is glycosylated; glycosylation may modulate DNA repair function.", "mechanism": "Pathogenic variants increase cancer risk.", "protein": "PALB2", "protein_enriched": { "function": "Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks (PubMed:16793542, PubMed:19369211, PubMed:19423707, PubMed:22941656, PubMed:", "gene_name": "PALB2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86YC2" }, "relationship_type": "causal", "source_pmcid": "PMC11771725" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "NS1 is heavily glycosylated, which affects its secretion and immune recognition.", "mechanism": "NS1 is secreted during dengue infection and detected in blood as a diagnostic marker.", "protein": "Non-structural protein 1 (NS1)", "protein_enriched": { "function": "Required in engulfing to control the phagocytosis of apoptotic cell corpses (PubMed:10707082, PubMed:20126385). Required in embryonic development for the correct positioning and orientation of the mit", "gene_name": "ced-10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03206" }, "relationship_type": "biomarker", "source_pmcid": "PMC11777499" }, { "confidence": "medium", "disease": "Severe dengue", "glycan_involvement": "Glycosylation modulates NS1 stability and pathogenicity.", "mechanism": "High levels of NS1 correlate with severe dengue and complications.", "protein": "Non-structural protein 1 (NS1)", "protein_enriched": { "function": "Required in engulfing to control the phagocytosis of apoptotic cell corpses (PubMed:10707082, PubMed:20126385). Required in embryonic development for the correct positioning and orientation of the mit", "gene_name": "ced-10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03206" }, "relationship_type": "biomarker", "source_pmcid": "PMC11777499" }, { "confidence": "high", "disease": "Paradoxical psoriasis (PP)", "glycan_involvement": "IL-23R is a glycoprotein; glycosylation may affect receptor function and immune signaling.", "mechanism": "IL23R1142G>A variant increases susceptibility to anti-TNF\u03b1 induced PP in IBD patients.", "protein": "Interleukin-23 receptor (IL-23R)", "protein_enriched": { "function": "Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-", "gene_name": "IL23R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q5VWK5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807522" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may modulate IL-23R signaling in skin inflammation.", "mechanism": "Genetic variation in IL23R linked to psoriasis onset.", "protein": "Interleukin-23 receptor (IL-23R)", "protein_enriched": { "function": "Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-", "gene_name": "IL23R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q5VWK5" }, "relationship_type": "causal", "source_pmcid": "PMC11807522" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "TNF\u03b1 is glycosylated; glycosylation may affect cytokine stability and receptor binding.", "mechanism": "Anti-TNF\u03b1 therapy is used to treat IBD.", "protein": "Tumor necrosis factor alpha (TNF\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11807522" }, { "confidence": "high", "disease": "Paradoxical psoriasis (PP)", "glycan_involvement": "Glycosylation of TNF\u03b1 may influence immune response and adverse effects.", "mechanism": "Anti-TNF\u03b1 therapy can induce PP as an adverse effect.", "protein": "Tumor necrosis factor alpha (TNF\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC11807522" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Glycosylation may affect IL-23R function in gut immunity.", "mechanism": "IL23R variant may stratify risk for anti-TNF\u03b1 induced PP in IBD patients.", "protein": "Interleukin-23 receptor (IL-23R)", "protein_enriched": { "function": "Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-", "gene_name": "IL23R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q5VWK5" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807522" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "CRP levels correlate with systemic inflammation and are elevated in pre-clinical and established Crohn's disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807523" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "No direct glycosylation; cysteine may influence redox-sensitive glycoprotein function.", "mechanism": "Higher serum cysteine (reduced form) is negatively associated with future risk of Crohn's disease.", "protein": "Cysteine", "relationship_type": "protective", "source_pmcid": "PMC11807523" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "No direct glycosylation; may affect glycoprotein redox status.", "mechanism": "Elevated cysteine sulfinic acid (oxidized form) is positively associated with future risk of Crohn's disease and correlates with inflammation.", "protein": "Cysteine sulfinic acid", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11807523" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "CRP glycosylation may modulate its inflammatory activity.", "mechanism": "CRP levels are positively correlated with cysteine sulfinic acid and negatively with cysteine, reflecting oxidative stress and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807523" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "O-glycosylation of Muc2 is essential for mucus barrier integrity.", "mechanism": "Muc2 forms the colonic mucus barrier preventing E. coli pathobiont adherence and inflammation.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC11807543" }, { "confidence": "high", "disease": "Colitis (experimental)", "glycan_involvement": "Loss of O-glycans on Muc2 compromises mucus barrier.", "mechanism": "Impaired or reduced glycosylation of Muc2 leads to thinner mucus, allowing E. coli pathobiont to reach epithelium and induce colitis.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11807543" }, { "confidence": "high", "disease": "Colitis (experimental)", "glycan_involvement": "Core 1 O-glycan synthesis is disrupted, affecting Muc2 structure.", "mechanism": "Genetic deficiency of C1galt1 in IECs reduces core 1 O-glycans, impairing mucin glycosylation and mucus barrier.", "protein": "C1galt1", "protein_enriched": { "function": "May be involved in the fusion of the spermatozoa with the oocyte during fertilization", "gene_name": "Cd46", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O88174" }, "relationship_type": "causal", "source_pmcid": "PMC11807543" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Altered O-glycosylation patterns in Muc2.", "mechanism": "Impaired Muc2 glycosylation is frequently observed in UC patients.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11807543" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Therapies could target O-glycosylation pathways.", "mechanism": "Restoring Muc2 glycosylation or mucus thickness may reduce susceptibility to UC pathobionts.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11807543" }, { "confidence": "high", "disease": "Bacterial translocation", "glycan_involvement": "O-glycosylation of mucins forms mucus barrier; disruption may allow bacterial passage.", "mechanism": "Bacteria invade and co-localize with goblet cells, suggesting mucin glycoproteins may facilitate or be breached during translocation.", "protein": "Goblet cell mucins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "medium", "disease": "Anxiety-like behavior", "glycan_involvement": "Altered mucin glycosylation may affect barrier integrity and neuroimmune signaling.", "mechanism": "Bacterial invasion of goblet cells correlates with increased anxiety-like behavior in stressed mice.", "protein": "Goblet cell mucins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "medium", "disease": "Depression-like behavior", "glycan_involvement": "Mucin glycosylation status may modulate susceptibility to bacterial invasion.", "mechanism": "Enhanced bacterial translocation via goblet cells is associated with depression-like behavior.", "protein": "Goblet cell mucins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "medium", "disease": "Bacterial translocation", "glycan_involvement": "Glycosylation of integrins may regulate cell trafficking and bacterial uptake.", "mechanism": "Bacteria found within CD103+ cells suggest these glycoproteins may mediate immune cell-associated translocation.", "protein": "CD103+ cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "low", "disease": "Anxiety-like behavior", "glycan_involvement": "Glycosylation may affect immune signaling to the CNS.", "mechanism": "Presence of bacteria in CD103+ cells correlates with stress-induced behavioral changes.", "protein": "CD103+ cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "low", "disease": "Anxiety-like behavior", "glycan_involvement": "Neuronal glycoprotein glycosylation may modulate neuroinflammation.", "mechanism": "Bacteria in close proximity to neurons in stressed mice suggest possible glycoprotein-mediated neuroimmune interaction.", "protein": "Neuronal glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "low", "disease": "Depression-like behavior", "glycan_involvement": "Altered glycosylation could affect neuronal response to inflammation.", "mechanism": "Bacterial proximity to neurons may contribute to depression-like behavior via glycoprotein-mediated signaling.", "protein": "Neuronal glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11807597" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "IgG1 is N-glycosylated, which modulates effector function and inflammation", "mechanism": "Increased IgG1-producing B cells and serum IgG1 in colitis; promotes inflammation", "protein": "IgG1", "relationship_type": "biomarker", "source_pmcid": "PMC11807608" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "IgG2b is N-glycosylated, influencing immune complex formation", "mechanism": "Serum IgG2b levels increased in colitic mice; associated with inflammation", "protein": "IgG2b", "relationship_type": "biomarker", "source_pmcid": "PMC11807608" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "IgG2c is N-glycosylated, affecting Fc receptor binding", "mechanism": "Serum IgG2c levels increased and IgA/IgG2c ratio decreased in colon tissue; linked to inflammation", "protein": "IgG2c", "relationship_type": "biomarker", "source_pmcid": "PMC11807608" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "IgA is heavily glycosylated (N- and O-glycans), critical for mucosal immunity", "mechanism": "IgA-producing B cells increased in Peyer's patches; IgA/IgG2c ratio decreased in colon tissue, suggesting impaired mucosal protection", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC11807608" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "CD19 is N-glycosylated, affecting B cell signaling", "mechanism": "Aggregated CD19+ B cells increased in inflamed colon; marker of B cell expansion", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807608" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "CD86 is N-glycosylated, modulating T cell co-stimulation", "mechanism": "Increased CD86+ B cells in colon, Peyer's patches, and MLN; marker of B cell activation", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11807608" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Baff is glycosylated, which may affect secretion and receptor interaction", "mechanism": "Baff mRNA upregulated in colitis; promotes B cell survival and activation", "protein": "Baff (TNFSF13B)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11807608" }, { "confidence": "low", "disease": "Ulcerative colitis", "glycan_involvement": "CD80 is N-glycosylated, influencing immune synapse formation", "mechanism": "CD80 expression assessed as B cell activation marker in inflamed tissue", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC11807608" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Heavily O-glycosylated, with >100 unique glycans including Sia\u03b12,6Gal capping structures.", "mechanism": "MUC2 forms the mucus barrier protecting the colon from inflammation.", "protein": "Mucin-2 (MUC2)", "relationship_type": "protective", "source_pmcid": "PMC11807625" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "ST6Gal1 mediates \u03b12,6-sialylation of galactose on MUC2 glycans.", "mechanism": "Loss of ST6Gal1 in gut epithelium increases susceptibility to colitis in a sex-specific manner.", "protein": "ST6Gal1", "relationship_type": "causal", "source_pmcid": "PMC11807625" }, { "confidence": "high", "disease": "Microbially-induced inflammation", "glycan_involvement": "Sia\u03b12,6Gal capping structures interact with gut microbiota.", "mechanism": "MUC2 glycosylation modulates microbiota and prevents inflammation.", "protein": "Mucin-2 (MUC2)", "relationship_type": "protective", "source_pmcid": "PMC11807625" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Loss of Sia\u03b12,6Gal alters mucin glycosylation and sulfation.", "mechanism": "Female IEC St6gal1-/- mice show altered mucin sulfation and more severe bacterial-induced colitis.", "protein": "ST6Gal1", "relationship_type": "causal", "source_pmcid": "PMC11807625" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Loss of Sia\u03b12,6Gal affects mucus glycosylation and microbiota composition.", "mechanism": "Male IEC St6gal1-/- mice show mildly worsened DSS-induced colitis.", "protein": "ST6Gal1", "relationship_type": "causal", "source_pmcid": "PMC11807625" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Altered sialylation and sulfation patterns on MUC2.", "mechanism": "Glycomic changes in MUC2 correlate with colitis susceptibility.", "protein": "Mucin-2 (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC11807625" }, { "confidence": "medium", "disease": "Microbially-induced inflammation", "glycan_involvement": "Sia\u03b12,6Gal on MUC2 modulates microbial ecology.", "mechanism": "Loss of Sia\u03b12,6Gal alters microbiota composition, increasing Firmicutes in males and reducing Bifidobacterium spp.", "protein": "ST6Gal1", "relationship_type": "causal", "source_pmcid": "PMC11807625" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Female mice show altered mucin sulfation when Sia\u03b12,6Gal is lost.", "mechanism": "Sex-specific glycosylation of MUC2 influences colitis outcomes.", "protein": "Mucin-2 (MUC2)", "relationship_type": "protective", "source_pmcid": "PMC11807625" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "ST6Gal1-dependent sialylation is protective.", "mechanism": "Restoring ST6Gal1 activity may protect against colitis.", "protein": "ST6Gal1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11807625" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "Sialylation and sulfation status as biomarkers.", "mechanism": "Sex-specific glycomic signatures of MUC2 may indicate colitis risk.", "protein": "Mucin-2 (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC11807625" }, { "confidence": "high", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Altered glycosylation (fucosylation and sialylation) affects mucin barrier function.", "mechanism": "Mucin layer integrity is critical for defense against CR infection; depletion leads to increased susceptibility.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC11807659" }, { "confidence": "high", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Tollip deficiency leads to altered mucin glycosylation (decreased fucosylation, increased sialylation).", "mechanism": "Tollip promotes mucin production and proper glycosylation, aiding in pathogen clearance.", "protein": "Toll-interacting protein (Tollip)", "relationship_type": "protective", "source_pmcid": "PMC11807659" }, { "confidence": "medium", "disease": "Diarrheic enterocolitis", "glycan_involvement": "Glycosylation changes impact mucus barrier properties.", "mechanism": "Goblet cell depletion and mucin barrier thinning contribute to diarrheic enterocolitis.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC11807659" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Fucosylation and sialylation changes modulate inflammatory response.", "mechanism": "Reduced mucin production and altered glycosylation exacerbate colonic inflammation.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC11807659" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Regulates glycosylation patterns of mucins.", "mechanism": "Tollip supports mucin barrier integrity, limiting epithelial damage and inflammation.", "protein": "Toll-interacting protein (Tollip)", "relationship_type": "protective", "source_pmcid": "PMC11807659" }, { "confidence": "medium", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Lectin staining reveals glycosylation changes during infection.", "mechanism": "Altered mucin glycosylation patterns (fucosylation/sialylation) indicate infection status.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC11807659" }, { "confidence": "low", "disease": "Diarrheic enterocolitis", "glycan_involvement": "Affects mucin glycosylation and secretion.", "mechanism": "Tollip deficiency may predispose to enterocolitis via impaired mucin barrier.", "protein": "Toll-interacting protein (Tollip)", "relationship_type": "protective", "source_pmcid": "PMC11807659" }, { "confidence": "low", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Targeting fucosylation/sialylation pathways.", "mechanism": "Restoring mucin glycosylation may improve barrier function and pathogen clearance.", "protein": "Mucin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11807659" }, { "confidence": "low", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Reflects glycosylation-dependent barrier defects.", "mechanism": "Delayed bacterial clearance in Tollip-deficient mice marks impaired mucin barrier.", "protein": "Toll-interacting protein (Tollip)", "relationship_type": "biomarker", "source_pmcid": "PMC11807659" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "Lectin-based detection of glycan changes.", "mechanism": "Mucin glycosylation status correlates with colitis severity.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC11807659" }, { "confidence": "high", "disease": "Major depressive disorder", "glycan_involvement": "N-glycosylation is required for proper folding, trafficking, and function of 5-HT2A receptor.", "mechanism": "Activation by serotonergic psychedelics (psilocin, DOI, TCB-2) mediates antidepressant-like effects in mice.", "protein": "5-HT2A receptor", "protein_enriched": { "function": "G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as", "gene_name": "HTR2A", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P28223" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11814762" }, { "confidence": "medium", "disease": "Anxiety-related disorders", "glycan_involvement": "N-glycosylation may modulate receptor surface expression and ligand binding.", "mechanism": "Psilocin reduces anxiety-like behavior via 5-HT2A activation; effect not antagonized by volinanserin, suggesting partial involvement.", "protein": "5-HT2A receptor", "protein_enriched": { "function": "G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as", "gene_name": "HTR2A", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P28223" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11814762" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "HBsAg is heavily glycosylated, affecting immune recognition.", "mechanism": "HBsAg is a marker of active HBV infection and viral replication.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation of HBsAg modulates immunogenicity and autoimmunity.", "mechanism": "Chronic HBV infection can trigger secondary ITP via immune dysregulation.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC11815121" }, { "confidence": "high", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies target platelet glycoproteins, leading to platelet destruction.", "protein": "Platelet glycoprotein IIb/IIIa", "relationship_type": "causal", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "IgG/IgM glycosylation modulates immune complex formation.", "mechanism": "Elevated RF indicates underlying autoimmune activation.", "protein": "Rheumatoid factor (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation influences immune recognition and cell maturation.", "mechanism": "Autoantibodies inhibit megakaryocytopoiesis via glycoprotein targeting.", "protein": "Megakaryocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Cerebral microbleeds", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects clearance.", "mechanism": "Elevated D-dimer reflects increased fibrinolysis and risk of microbleeds in ITP.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11815121" }, { "confidence": "low", "disease": "Fatty liver", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Elevated AST indicates liver injury, often seen in HBV infection and fatty liver.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC11815121" }, { "confidence": "low", "disease": "Fatty liver", "glycan_involvement": "Glycosylation may influence enzyme secretion.", "mechanism": "Elevated ALT is a marker of hepatocellular injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Cerebral microbleeds", "glycan_involvement": "Glycosylation modulates platelet aggregation and immune clearance.", "mechanism": "Platelet dysfunction due to glycoprotein-targeting autoantibodies increases microbleed risk.", "protein": "Platelet glycoprotein IIb/IIIa", "relationship_type": "causal", "source_pmcid": "PMC11815121" }, { "confidence": "low", "disease": "Refractory bipolar disorder", "glycan_involvement": "Glycosylation of HBsAg influences neuroimmune interactions.", "mechanism": "HBV-induced immune dysregulation may exacerbate psychiatric symptoms.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC11815121" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Hemoglobin is a glycoprotein; however, the study does not specify glycosylation changes as the mechanism.", "mechanism": "Altered oxyhemoglobin waveforms in the frontal and temporal regions detected by fNIRS distinguish MDD patients from healthy controls.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11815140" }, { "confidence": "medium", "disease": "Bipolar Disorder", "glycan_involvement": "Hemoglobin glycosylation status not directly assessed; involvement inferred from glycoprotein nature.", "mechanism": "Distinct oxyhemoglobin waveform patterns in BP patients compared to healthy controls, as measured by fNIRS.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11815140" }, { "confidence": "high", "disease": "BBB dysfunction", "glycan_involvement": "gp120 is heavily glycosylated; glycosylation mediates receptor binding and immune evasion.", "mechanism": "gp120 increases endothelial cytotoxicity, permeability, and monocyte transmigration; disrupts tight junctions via MMP activation.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "high", "disease": "BBB dysfunction", "glycan_involvement": "Tat is O-glycosylated, which may affect its secretion and activity.", "mechanism": "Tat decreases tight junction protein expression, increases permeability, induces ROS and MMP-9 activity.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "high", "disease": "BBB dysfunction", "glycan_involvement": "Nef is glycosylated; glycosylation may affect its stability and interaction with host proteins.", "mechanism": "Nef induces endothelial apoptosis and increases BBB permeability via MMP-dependent pathways.", "protein": "Nef", "protein_enriched": { "function": "Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host ", "gene_name": "nef", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03407" }, "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "HAND", "glycan_involvement": "PDGFR-\u03b2 is N-glycosylated, affecting receptor function and signaling.", "mechanism": "Reduced PDGFR-\u03b2 expression in pericytes correlates with decreased vascular coverage and BBB instability in HIV.", "protein": "PDGFR-\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "Amyloid pathology", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation modulates processing and A\u03b2 generation.", "mechanism": "HIV/Tat alters APP cleavage, increasing A\u03b2 production and deposition.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "BBB dysfunction", "glycan_involvement": "A\u03b2 derives from glycosylated APP; glycosylation status affects aggregation and clearance.", "mechanism": "A\u03b2 is toxic to endothelial cells, increasing permeability, ROS, and apoptosis.", "protein": "A\u03b2 (Amyloid-beta)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "A\u03b2 accumulation", "glycan_involvement": "RAGE is N-glycosylated, influencing ligand binding and signaling.", "mechanism": "HIV increases RAGE expression in brain ECs, enhancing A\u03b2 uptake and transcytosis.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "BBB dysfunction", "glycan_involvement": "VE-Cadherin is N-glycosylated, essential for junction stability.", "mechanism": "Tat induces phosphorylation of VE-Cadherin, destabilizing endothelial junctions.", "protein": "VE-Cadherin", "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "Drug-induced BBB disruption", "glycan_involvement": "ALCAM is N-glycosylated, modulating adhesion and transmigration.", "mechanism": "Cocaine activates ALCAM on ECs, enhancing monocyte transmigration into CNS.", "protein": "ALCAM", "relationship_type": "causal", "source_pmcid": "PMC11823645" }, { "confidence": "medium", "disease": "Neuroprotection (in context of cannabinoids)", "glycan_involvement": "GLT1 is glycosylated, affecting transporter localization and function.", "mechanism": "Cannabinoids upregulate GLT1, restoring glutamate homeostasis and protecting neurons in HIV.", "protein": "GLT1 (EAAT2)", "protein_enriched": { "function": "Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:20477940, PubMed:26690923, PubMed:28032905, PubMed:28424515,", "gene_name": "SLC1A3", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11101UV", "G20706XG", "G53434XO", "G64409MC" ], "uniprot_id": "P43003" }, "relationship_type": "protective", "source_pmcid": "PMC11823645" }, { "confidence": "high", "disease": "Differentiated Thyroid Carcinoma", "glycan_involvement": "Glycosylation affects thyroglobulin stability and immunogenicity, impacting assay accuracy.", "mechanism": "Serum thyroglobulin is used to monitor recurrence and treatment response in DTC.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC11831906" }, { "confidence": "high", "disease": "Medullary Thyroid Carcinoma", "glycan_involvement": "Glycosylation modulates calcitonin secretion and half-life.", "mechanism": "Elevated serum calcitonin is a diagnostic and prognostic marker for MTC.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC11831906" }, { "confidence": "high", "disease": "Medullary Thyroid Carcinoma", "glycan_involvement": "CEA is heavily glycosylated; glycan structures influence detection and function.", "mechanism": "CEA is elevated in MTC and used for disease monitoring.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11831906" }, { "confidence": "medium", "disease": "Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma", "glycan_involvement": "N-glycosylation regulates integrin function and ligand binding.", "mechanism": "Integrin \u03b1v\u03b23 is upregulated in tumor angiogenesis and metastasis; targeted by RGD imaging.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11831906" }, { "confidence": "medium", "disease": "Medullary Thyroid Carcinoma", "glycan_involvement": "Glycosylation affects SSTR trafficking and ligand affinity.", "mechanism": "SSTR expression enables imaging and peptide receptor radionuclide therapy (PRRT) in MTC.", "protein": "Somatostatin Receptor (SSTR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11831906" }, { "confidence": "medium", "disease": "Congenital Hypothyroidism", "glycan_involvement": "N-glycosylation is essential for thyroglobulin folding and secretion.", "mechanism": "Defects in thyroglobulin synthesis or glycosylation can cause dyshormonogenesis and CH.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "causal", "source_pmcid": "PMC11831906" }, { "confidence": "medium", "disease": "Multiple Endocrine Neoplasia type 2 (MEN2)", "glycan_involvement": "Glycosylation may influence calcitonin immunoreactivity.", "mechanism": "Calcitonin is used for early detection of MTC in MEN2 patients.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC11831906" }, { "confidence": "low", "disease": "Differentiated Thyroid Carcinoma", "glycan_involvement": "Glycosylation impacts CEA serum levels and detection.", "mechanism": "CEA may be elevated in advanced DTC, aiding in disease monitoring.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11831906" }, { "confidence": "low", "disease": "Differentiated Thyroid Carcinoma", "glycan_involvement": "N-glycosylation modulates integrin-mediated signaling.", "mechanism": "Integrin \u03b1v\u03b23 imaging reflects tumor angiogenesis in DTC.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11831906" }, { "confidence": "low", "disease": "Multiple Endocrine Neoplasia type 2 (MEN2)", "glycan_involvement": "Glycosylation affects SSTR expression and imaging efficacy.", "mechanism": "SSTR imaging aids in detection of neuroendocrine tumors in MEN2.", "protein": "Somatostatin Receptor (SSTR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11831906" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation affects P-gp trafficking and function at the blood-brain barrier.", "mechanism": "Polymorphisms in ABCB1 gene affect CNS drug concentrations and response to antipsychotics.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC11837127" }, { "confidence": "high", "disease": "Infantile-onset Pompe disease (IOPD)", "glycan_involvement": "Glycosylation patterns of recombinant GAA affect immunogenicity and cellular uptake.", "mechanism": "Recombinant GAA replacement therapy can trigger immune response (ADA) in CRIM+ patients.", "protein": "Acid alpha-glucosidase (GAA)", "relationship_type": "therapeutic target", "source_pmcid": "PMC11837127" }, { "confidence": "medium", "disease": "Drug-induced CNS adverse reactions", "glycan_involvement": "Glycosylation modulates receptor trafficking and function.", "mechanism": "Diazepam exposure increases GABA-A receptor expression, altering neurotransmission and behavior.", "protein": "GABA-A receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11837127" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation required for DAT surface expression and activity.", "mechanism": "Pesticide exposure (rotenone, deltamethrin) induces dopaminergic neuron loss in zebrafish.", "protein": "Dopamine transporter (DAT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, Pu", "gene_name": "SLC6A3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q01959" }, "relationship_type": "biomarker", "source_pmcid": "PMC11837127" }, { "confidence": "medium", "disease": "T-cell lymphoma (post-CAR-T)", "glycan_involvement": "CAR constructs are glycoproteins; glycosylation may affect immunogenicity and stability.", "mechanism": "Integration of CAR transgene detected in malignant T-cell clones post-CAR-T therapy.", "protein": "CAR transgene (Chimeric Antigen Receptor)", "relationship_type": "causal", "source_pmcid": "PMC11837127" }, { "confidence": "medium", "disease": "Immunogenicity in ATMPs", "glycan_involvement": "Fc glycosylation modulates antibody effector function and immunogenicity.", "mechanism": "In silico prediction of T cell epitopes in antibody sequences to assess immunogenicity risk.", "protein": "Antibody (general)", "relationship_type": "biomarker", "source_pmcid": "PMC11837127" }, { "confidence": "high", "disease": "Immune-mediated adverse reactions (ADA in IOPD)", "glycan_involvement": "Glycosylation influences antigen processing and presentation.", "mechanism": "Mismatch in T cell epitopes between native and replacement GAA triggers ADA formation.", "protein": "Acid alpha-glucosidase (GAA)", "relationship_type": "causal", "source_pmcid": "PMC11837127" }, { "confidence": "medium", "disease": "Drug-induced CNS adverse reactions", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux pump limits CNS drug entry, reducing neurotoxicity risk.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "protective", "source_pmcid": "PMC11837127" }, { "confidence": "low", "disease": "Autism spectrum disorders (in utero exposure)", "glycan_involvement": "Glycosylation affects receptor assembly and synaptic localization.", "mechanism": "Altered GABAergic signaling implicated in neurodevelopmental disorders after antiepileptic drug exposure.", "protein": "GABA-A receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11837127" }, { "confidence": "low", "disease": "Nephritis/hepatitis (DRESS)", "glycan_involvement": "Glycosylation may modulate immunogenicity of therapeutic proteins.", "mechanism": "Immune response to drug or replacement protein can trigger systemic symptoms.", "protein": "Acid alpha-glucosidase (GAA)", "relationship_type": "causal", "source_pmcid": "PMC11837127" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates spike protein binding and viral entry efficiency.", "mechanism": "ACE2 acts as the primary receptor for SARS-CoV-2 entry into host cells, including liver and GI tract cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated, impacting host cell recognition and immune response.", "mechanism": "Spike protein binds ACE2 to mediate viral entry; glycosylation shields RBD and affects immune evasion.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "Minor glycosylation may affect stability, but not central to biomarker role.", "mechanism": "Elevated ALT indicates liver injury in COVID-19 patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "Minor glycosylation; not central to disease association.", "mechanism": "Elevated AST is common in COVID-19 and correlates with severity and mortality.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "N-glycosylation affects ALP stability and secretion.", "mechanism": "Elevated ALP reflects cholestatic liver injury in COVID-19.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "Minimal glycosylation; not central to biomarker function.", "mechanism": "Low albumin is associated with poor prognosis in COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "medium", "disease": "Gastrointestinal manifestations", "glycan_involvement": "Glycosylation of ACE2 modulates viral binding in GI cells.", "mechanism": "ACE2 expression in GI tract enables SARS-CoV-2 infection, leading to GI symptoms.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Minor glycosylation; not central to biomarker role.", "mechanism": "Elevated ALT is associated with increased severity and mortality in COVID-19.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Minor glycosylation; not central to biomarker role.", "mechanism": "Elevated AST is associated with increased severity and mortality in COVID-19.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC11837814" }, { "confidence": "medium", "disease": "Cirrhosis of the liver", "glycan_involvement": "Altered glycosylation in cirrhotic tissue may affect ACE2 function.", "mechanism": "ACE2 expression in cirrhotic liver may facilitate SARS-CoV-2 infection, worsening outcomes.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11837814" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "GPX-3 is a glycoprotein; glycosylation is required for its secretion and stability in plasma.", "mechanism": "Serum GPX-3 concentration inversely correlates with vasculitis activity and damage at diagnosis; lower GPX-3 reflects higher oxidative stress and inflammation.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Glycosylation enables extracellular localization and function.", "mechanism": "GPX-3 scavenges ROS, reducing vascular inflammation and tissue damage.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "protective", "source_pmcid": "PMC11842223" }, { "confidence": "medium", "disease": "Inflammatory diseases (general)", "glycan_involvement": "Glycosylation is essential for plasma stability.", "mechanism": "Low serum GPX-3 is associated with high inflammation and poor prognosis.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "low", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "Low GPX-3 levels are linked to poor prognosis in cancer patients due to reduced antioxidant capacity.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "low", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation required for plasma activity.", "mechanism": "APS patients may exhibit decreased GPX-3 due to increased ROS production and oxidative stress.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation modulates antigenicity and immune recognition.", "mechanism": "\u03b22GPI is the antigenic target for antiphospholipid antibodies, triggering endothelial activation and thrombosis.", "protein": "\u03b22-glycoprotein-I (\u03b22GPI)", "relationship_type": "causal", "source_pmcid": "PMC11842223" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Glycosylation supports plasma stability.", "mechanism": "Serum GPX-3 correlates with acute-phase reactants (CRP, albumin), reflecting inflammatory burden.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Glycosylation not directly linked to outcome prediction.", "mechanism": "Serum GPX-3 is not predictive of poor outcomes (mortality, ESKD, CVA, ACS) during follow-up.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Lower GPX-3 is associated with general constitutional symptoms (myalgia, fever, weight loss) at diagnosis.", "protein": "Glutathione peroxidase-3 (GPX-3)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Detection of anti-\u03b22GPI antibodies is diagnostic for APS.", "protein": "\u03b22-glycoprotein-I (\u03b22GPI)", "relationship_type": "biomarker", "source_pmcid": "PMC11842223" }, { "confidence": "high", "disease": "Solid Tumors", "glycan_involvement": "ADP is a glycoprotein; glycosylation may affect its stability and cell lysis function.", "mechanism": "ADP overexpression in oncolytic adenovirus enhances tumor cell lysis and viral spread.", "protein": "Adenovirus Death Protein (ADP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "PD-L1 is glycosylated, which can modulate its stability and immune evasion.", "mechanism": "PD-L1 on tumor cells inhibits T cell function; blocking PD-L1 with antibodies or engineered viruses enhances immune-mediated tumor destruction.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "high", "disease": "General Cancer (multiple types)", "glycan_involvement": "CTLA-4 glycosylation affects its cell surface expression and immune regulation.", "mechanism": "CTLA-4 inhibits T cell activation; blockade (e.g., with Ipilimumab) in combination with oncolytic virus boosts anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "medium", "disease": "Malignant Pleural Mesothelioma", "glycan_involvement": "MHC-I is heavily glycosylated, impacting antigen presentation.", "mechanism": "MHC-I presentation by dendritic cells activates CD8+ T cells after oncolytic virus therapy.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11842258" }, { "confidence": "high", "disease": "Breast Cancer Brain Metastases", "glycan_involvement": "EGFR glycosylation modulates receptor function and antibody recognition.", "mechanism": "EGFR-CAR NK cells combined with oncolytic HSV show enhanced killing of EGFR+ tumor cells.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "IL-15R\u03b1 glycosylation affects receptor stability and signaling.", "mechanism": "Oncolytic viruses expressing IL-15/IL-15R\u03b1 enhance CAR-NK cell anti-tumor activity.", "protein": "IL-15/IL-15R\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "IFN\u03b3 glycosylation may affect secretion and activity.", "mechanism": "NDV engineered to promote IFN\u03b3 release from infected melanoma cells boosts anti-tumor immunity.", "protein": "IFN\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "high", "disease": "Solid Tumors", "glycan_involvement": "PD-L1 glycosylation influences antibody binding and immune evasion.", "mechanism": "Oncolytic viruses expressing PD-L1 blocking micro-antibodies with CAR-T cells control solid tumor growth.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "medium", "disease": "Solid Tumors", "glycan_involvement": "RANTES glycosylation affects chemokine activity and cell migration.", "mechanism": "Oncolytic viruses expressing RANTES and IL-15 enhance CAR-T cell recruitment and tumor killing.", "protein": "RANTES (CCL5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "medium", "disease": "Hematologic Malignancies", "glycan_involvement": "CD3\u03b6 glycosylation may affect receptor assembly and signaling.", "mechanism": "CD3\u03b6 domain in CAR-T cells mediates T cell activation for tumor cell killing; oncolytic virus enhances CAR-T cell persistence.", "protein": "CD3\u03b6", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD247", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20963" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842258" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "GPI-anchor glycosylation required for membrane localization and function.", "mechanism": "CD109 deficiency or decreased expression leads to enhanced TGF-\u03b2/Smad and IL-23/IL-17 axis signaling, driving skin inflammation and hyperproliferation.", "protein": "CD109", "protein_enriched": { "function": "Modulates negatively TGFB1 signaling in keratinocytes", "gene_name": "CD109", "glycan_count": 107, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G27058EU", "G00912UN", "G01650EU", "G02815KT", "G08918WF", "G20312EM", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G46503DX", "G62765YT", "G70888PK", "G80920RR", "G92050GC", "G92406TI", 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"G62894KT", "G70101JE", "G95865ZB", "G49108TO", "G02528FI", "G80479JV", "G16125XL", "G68490OW", "G83633GK", "G13131HA", "G27915IV", "G37881RL", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G83646BJ", "G85282JO", "G87123QX", "G87661QW", "G05962QB", "G52096TR", "G69031IF", "G82443XX", "G20528HD", "G35541EV", "G44753VC", "G50856PC", "G84225JN", "G90382BL", "G93718GY" ], "uniprot_id": "Q6YHK3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11842317" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia", "glycan_involvement": "GPI-anchor glycosylation required for cell surface immune modulation.", "mechanism": "CD109 overexpression impairs T-cell activation via deregulation of TCR signaling and immune checkpoint molecules, promoting immune evasion.", "protein": "CD109", "protein_enriched": { "function": "Modulates negatively TGFB1 signaling in keratinocytes", "gene_name": "CD109", "glycan_count": 107, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G27058EU", "G00912UN", "G01650EU", "G02815KT", "G08918WF", "G20312EM", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G46503DX", "G62765YT", "G70888PK", "G80920RR", "G92050GC", "G92406TI", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G23294PN", "G25451PN", "G27947YN", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G49906RN", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G65184UU", "G66163OV", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G80075MS", "G81263BG", "G84452RH", "G86880BF", "G90659AW", "G00273SJ", "G04657PL", "G10846ZT", "G14972EH", "G20956ZV", "G27126ED", "G40926MX", "G46691LC", "G59334JE", "G74724QE", "G83229XP", "G92135MA", "G05724UK", "G06110VR", "G11629QQ", "G39188ZX", "G41840AI", "G43089EG", "G56784JY", "G57888GL", "G59924QI", "G64527OM", "G08539HC", "G22310AV", "G47748JZ", "G87389XI", "G10019LZ", "G28622IK", "G35107SO", "G38663NM", "G52527GH", "G62461SM", "G62894KT", "G70101JE", "G95865ZB", "G49108TO", "G02528FI", "G80479JV", "G16125XL", "G68490OW", "G83633GK", "G13131HA", "G27915IV", "G37881RL", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G83646BJ", "G85282JO", "G87123QX", "G87661QW", "G05962QB", "G52096TR", "G69031IF", "G82443XX", "G20528HD", "G35541EV", "G44753VC", "G50856PC", "G84225JN", "G90382BL", "G93718GY" ], "uniprot_id": "Q6YHK3" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11842317" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "GPI-anchor glycosylation required for dendritic cell function.", "mechanism": "CD109 in dendritic cells promotes Th2 cytokine production and eosinophilic inflammation; deficiency reduces airway hyperreactivity.", "protein": "CD109", "protein_enriched": { "function": "Modulates negatively TGFB1 signaling in keratinocytes", "gene_name": "CD109", "glycan_count": 107, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G27058EU", "G00912UN", "G01650EU", "G02815KT", "G08918WF", "G20312EM", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G46503DX", "G62765YT", "G70888PK", "G80920RR", "G92050GC", "G92406TI", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G23294PN", "G25451PN", "G27947YN", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G49906RN", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G65184UU", "G66163OV", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G80075MS", "G81263BG", "G84452RH", "G86880BF", "G90659AW", "G00273SJ", "G04657PL", "G10846ZT", "G14972EH", "G20956ZV", "G27126ED", "G40926MX", "G46691LC", "G59334JE", "G74724QE", "G83229XP", "G92135MA", "G05724UK", "G06110VR", "G11629QQ", "G39188ZX", "G41840AI", "G43089EG", "G56784JY", "G57888GL", "G59924QI", "G64527OM", "G08539HC", "G22310AV", "G47748JZ", "G87389XI", "G10019LZ", "G28622IK", "G35107SO", "G38663NM", "G52527GH", "G62461SM", "G62894KT", "G70101JE", "G95865ZB", "G49108TO", "G02528FI", "G80479JV", "G16125XL", "G68490OW", "G83633GK", "G13131HA", "G27915IV", "G37881RL", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G83646BJ", "G85282JO", "G87123QX", "G87661QW", "G05962QB", "G52096TR", "G69031IF", "G82443XX", "G20528HD", "G35541EV", "G44753VC", "G50856PC", "G84225JN", "G90382BL", "G93718GY" ], "uniprot_id": "Q6YHK3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11842317" }, { "confidence": "high", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied; A20 is a putative glycoprotein.", "mechanism": "A20 protein levels are decreased in CD8+ T cells but increased in CD4+ T cells of PsA patients, despite elevated TNFAIP3 transcripts, suggesting translational inhibition.", "protein": "A20", "relationship_type": "biomarker", "source_pmcid": "PMC11842318" }, { "confidence": "high", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied; I\u03baB\u03b1 is a putative glycoprotein.", "mechanism": "I\u03baB\u03b1 protein levels are decreased in CD8+ T cells but increased in CD4+ T cells of PsA patients, despite elevated NFKBIA transcripts, indicating translational inhibition.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriasis (PsC)", "glycan_involvement": "Not directly studied.", "mechanism": "A20 protein and TNFAIP3 transcript levels are upregulated in CD4+ and CD8+ T cells in PsC compared to HC.", "protein": "A20", "relationship_type": "biomarker", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriasis (PsC)", "glycan_involvement": "Not directly studied.", "mechanism": "I\u03baB\u03b1 protein and NFKBIA transcript levels are upregulated in CD4+ T cells in PsC compared to HC.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied.", "mechanism": "A20 is a negative regulator of inflammation; translational inhibition in CD8+ T cells may contribute to PsA pathogenesis.", "protein": "A20", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied.", "mechanism": "I\u03baB\u03b1 inhibits NF-\u03baB signaling; translational inhibition in CD8+ T cells may drive inflammation in PsA.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied.", "mechanism": "Reduced A20 protein in CD8+ T cells may fail to suppress inflammation, contributing to PsA.", "protein": "A20", "relationship_type": "causal", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Psoriatic Arthritis (PsA)", "glycan_involvement": "Not directly studied.", "mechanism": "Reduced I\u03baB\u03b1 protein in CD8+ T cells may lead to unchecked NF-\u03baB activity and inflammation.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "causal", "source_pmcid": "PMC11842318" }, { "confidence": "low", "disease": "Psoriasis (PsC)", "glycan_involvement": "Not directly studied.", "mechanism": "Upregulation of A20 in T cells may help limit inflammation in PsC.", "protein": "A20", "relationship_type": "protective", "source_pmcid": "PMC11842318" }, { "confidence": "low", "disease": "Psoriasis (PsC)", "glycan_involvement": "Not directly studied.", "mechanism": "Upregulation of I\u03baB\u03b1 in T cells may help limit inflammation in PsC.", "protein": "I\u03baB\u03b1", "protein_enriched": { "function": "Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:3665180", "gene_name": "NFKBIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25963" }, "relationship_type": "protective", "source_pmcid": "PMC11842318" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "CA724 is a glycoprotein; glycosylation is essential for its biomarker function.", "mechanism": "CA724 levels measured as part of biochemical assessment in gout patients; no significant change with treatment.", "protein": "CA724", "relationship_type": "biomarker", "source_pmcid": "PMC11842343" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and function as an inflammatory marker.", "mechanism": "CRP used to monitor inflammation in gout; no significant change with urate-lowering therapy.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842343" }, { "confidence": "medium", "disease": "Cardiovascular Diseases", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased cardiovascular risk; relevant in gout patients due to comorbidity.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842343" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation affects CRP's clearance and function.", "mechanism": "CRP is used to monitor systemic inflammation, which is relevant in CKD and gout comorbidity.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842343" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "NT-proBNP is N-glycosylated, affecting its stability and plasma half-life.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and is used for risk stratification in ADHF.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "N-glycosylation modulates ICAM-1 cell surface expression and function.", "mechanism": "ICAM-1 mediates leukocyte adhesion and transmigration, contributing to cardiac inflammation and adverse outcomes.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycosylation affects IL-6 secretion and receptor binding.", "mechanism": "IL-6 is a pro-inflammatory cytokine elevated in ADHF, associated with increased mortality.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycosylation influences IL-10 stability and activity.", "mechanism": "IL-10 is anti-inflammatory, modulating local cardiac inflammation and potentially reducing mortality.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC11842369" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "N-glycosylation is essential for CRP secretion and function.", "mechanism": "CRP is an acute-phase glycoprotein elevated in ADHF, predictive of mortality.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIIb/IIIa) mediate adhesion and aggregation.", "mechanism": "Low platelet count is associated with increased mortality in ADHF.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "WBC surface glycoproteins (e.g., selectins, integrins) mediate immune cell trafficking.", "mechanism": "Elevated WBC count reflects systemic inflammation and is associated with poor prognosis.", "protein": "White Blood Cell (WBC)", "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation affects CRP function.", "mechanism": "Elevated CRP predicts adverse outcomes in stroke.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation modulates ICAM-1 function.", "mechanism": "ICAM-1 promotes leukocyte infiltration in cerebral ischemia.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC11842369" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation affects CRP stability.", "mechanism": "Elevated CRP is associated with increased risk and severity of diabetes.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842369" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Highly glycosylated; glycosylation affects exosome targeting and immune modulation.", "mechanism": "Exosomal CD63 modulates macrophage polarization, promoting anti-inflammatory M2 phenotype.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation may regulate CD81's interaction with signaling partners.", "mechanism": "Exosomal CD81 inhibits STAT1 activation, reducing M1 macrophage-driven inflammation.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "M1 macrophage-induced diseases", "glycan_involvement": "Glycosylation modulates ligand binding and immune signaling.", "mechanism": "CD80 is a marker of pro-inflammatory M1 macrophages; its reduction indicates therapeutic efficacy.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation affects receptor-ligand interactions.", "mechanism": "CD86 expression correlates with M1 polarization and inflammation; exosome treatment reduces CD86.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Tissue injury", "glycan_involvement": "C-type lectin glycosylation critical for ligand recognition and phagocytosis.", "mechanism": "CD206 upregulation by exosomes promotes M2 macrophages, aiding tissue repair.", "protein": "CD206 (MRC1)", "relationship_type": "protective", "source_pmcid": "PMC11842380" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates receptor stability and signaling.", "mechanism": "IL-6R is upregulated in M1 macrophages, driving inflammation; exosome treatment lowers IL-6R.", "protein": "IL-6R", "relationship_type": "causal", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Tissue injury", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Exosomal TGF-\u03b2 promotes M2 polarization and tissue regeneration.", "protein": "TGF-\u03b2", "relationship_type": "protective", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "Exosomal IL-10 induces anti-inflammatory responses, suppressing autoimmune pathology.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC11842380" }, { "confidence": "medium", "disease": "Tissue injury", "glycan_involvement": "Glycosylation may affect enzyme activity and localization.", "mechanism": "Arg-1 upregulation by exosomes supports M2 macrophage-mediated repair.", "protein": "Arg-1", "relationship_type": "protective", "source_pmcid": "PMC11842380" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Glycosylation essential for LPS binding and immune signaling.", "mechanism": "CD14 marks monocyte/macrophage activation; exosome therapy modulates its expression in injury.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842380" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "Env is heavily glycosylated, which is critical for receptor binding and immune evasion.", "mechanism": "HTLV-1 Env mediates viral entry into CD4+ T cells via GLUT1, initiating infection that can lead to ATLL.", "protein": "HTLV-1 envelope glycoprotein (Env)", "protein_enriched": { "function": "Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin l", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03356" }, "relationship_type": "causal", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "HTLV-1 infection", "glycan_involvement": "GLUT1 is N-glycosylated, which may affect Env binding.", "mechanism": "GLUT1 acts as a cellular receptor for HTLV-1 Env, facilitating viral entry.", "protein": "Glucose transporter 1 (GLUT1)", "relationship_type": "causal", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CD25 is N-glycosylated, which may affect stability and ligand binding.", "mechanism": "CD25 is highly expressed on ATLL cells and used for diagnosis.", "protein": "CD25 (IL-2 receptor alpha chain)", "relationship_type": "biomarker", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CCR4 is glycosylated, which may influence antibody binding.", "mechanism": "CCR4 is expressed on ATLL cells; targeted by mogamulizumab for therapy.", "protein": "CCR4", "protein_enriched": { "function": "High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calc", "gene_name": "CCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CD4 is N-glycosylated, affecting protein folding and function.", "mechanism": "ATLL cells are CD4+; CD4 is used for immunophenotyping.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842934" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CD30 is N-glycosylated, which may affect antibody recognition.", "mechanism": "CD30 is expressed in some ATLL cases; targeted by brentuximab vedotin.", "protein": "CD30", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "Beta-2 microglobulin is N-glycosylated, important for stability.", "mechanism": "Serum beta-2 microglobulin is elevated in ATLL and reflects tumor burden.", "protein": "Beta-2 microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC11842934" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CD7 is N-glycosylated; loss may affect cell signaling.", "mechanism": "Loss of CD7 expression is observed in ATLL and aids diagnosis.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842934" }, { "confidence": "medium", "disease": "Adult T-cell leukemia/lymphoma (ATLL)", "glycan_involvement": "CD26 is N-glycosylated, affecting enzymatic activity.", "mechanism": "Loss of CD26 expression is seen in ATLL and may help distinguish subtypes.", "protein": "CD26 (DPP4)", "protein_enriched": { "function": "Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:172872", "gene_name": "DPP4", "glycan_count": 92, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G10019LZ", "G12793SR", "G13131HA", "G22310AV", "G30740WO", "G41882MT", "G48414YA", "G57776ZS", "G57888GL", "G62461SM", "G82348BZ", "G22768VO", "G42227JK", "G56014GC", "G81315DD", "G81980VO", "G06356OH", "G56784JY", "G00395TQ", "G01650EU", "G02815KT", "G02886BB", "G10486CT", "G27058EU", "G28681TP", "G37399XV", "G46691LC", "G59626AS", "G72747WU", "G87661QW", "G92050GC", "G00912UN", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G15664MX", "G18647XP", "G20210JR", "G23294PN", "G23719VF", "G23984SE", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G29299MO", "G31852PQ", "G31986NC", "G37881RL", "G38663NM", "G39446WN", "G41071NU", "G41247ZX", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G47644PP", "G47748JZ", "G50282JC", "G59924QI", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G70441OD", "G70619PT", "G77547TA", "G80920RR", "G83646BJ", "G85269DF", "G86182NS", "G87123QX", "G90382BL", "G90659AW", "G92275SC", "G95865ZB", "G96091TT", "G40926MX", "G68490OW", "G74724QE", "G79666IR", "G84225JN", "G84452RH", "G49108TO" ], "uniprot_id": "P27487" }, "relationship_type": "biomarker", "source_pmcid": "PMC11842934" }, { "confidence": "medium", "disease": "Cutaneous T-cell lymphoma", "glycan_involvement": "Glycosylation may modulate antibody binding.", "mechanism": "CCR4 is expressed in cutaneous T-cell lymphomas, including ATLL; targeted by mogamulizumab.", "protein": "CCR4", "protein_enriched": { "function": "High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calc", "gene_name": "CCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11842934" }, { "confidence": "high", "disease": "Aortic Dissection", "glycan_involvement": "CXCL1 is a glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Elevated CXCL1 promotes neutrophil infiltration, leading to inflammation and destabilization of the aortic wall.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843136" }, { "confidence": "high", "disease": "Aortic Dissection", "glycan_involvement": "TIMP1 glycosylation affects its inhibitory function and stability.", "mechanism": "Regulates MMP activity, influencing ECM degradation and aortic wall stability.", "protein": "TIMP1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Aortic Dissection", "glycan_involvement": "Integrin glycosylation modulates cell adhesion and signaling.", "mechanism": "Upregulated ITGA5 contributes to ECM remodeling and aortic wall maintenance.", "protein": "ITGA5", "protein_enriched": { "function": "Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct ", "gene_name": "ITGA5", "glycan_count": 121, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G00912UN", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G45395BF", "G46503DX", "G46691LC", "G55220VL", "G57776ZS", "G80075MS", "G81315DD", "G84452RH", "G90659AW", "G11629QQ", "G48905WL", "G55132BD", "G22768VO", "G09724ZC", "G64481DJ", "G83473RC", "G06356OH", "G15169WU", "G22310AV", "G31916IQ", "G47518TP", "G48414YA", "G52527GH", "G55412XP", "G10404TD", "G62765YT", "G80920RR", "G93718GY", "G02815KT", "G05049YU", "G28541PG", "G31852PQ", "G41247ZX", "G62461SM", "G72747WU", "G41891LD", "G13694XX", "G14796IU", "G33791AF", "G47748JZ", "G56784JY", "G81263BG", "G81637OR", "G89865VY", "G22573RC", "G12604EW", "G14994KB", "G18647XP", "G25703UN", "G34617SM", "G40834TG", "G41071NU", "G43223CG", "G45495MK", "G57818FI", "G59324HL", "G60033FS", "G61627IG", "G70441OD", "G70619PT", "G75568BH", "G75983OB", "G79666IR", "G87123QX", "G90382BL", "G92135MA", "G57321FI", "G06110VR", "G11041DA", "G11870QZ", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G23863VK", "G25520XG", "G29880MM", "G36191CD", "G39188ZX", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48954CA", "G50045TK", "G50489VC", "G53752TA", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G72797UR", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G90093AU", "G91365ZQ", "G91413ZX", "G91636VS", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P08648" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843136" }, { "confidence": "high", "disease": "Aortic Dissection", "glycan_involvement": "PTX3 glycosylation influences its immune recognition and clearance.", "mechanism": "PTX3 is upregulated during vascular inflammation, marking acute inflammatory response in AD.", "protein": "PTX3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Aortic Aneurysm", "glycan_involvement": "Glycosylation may regulate CXCL1's chemotactic activity.", "mechanism": "CXCL1 promotes neutrophil recruitment and local inflammation, contributing to aneurysm formation.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Aortic Aneurysm", "glycan_involvement": "Glycosylation affects PTX3's stability and immune function.", "mechanism": "PTX3 is overexpressed in ruptured aneurysm tissue, indicating vascular inflammation.", "protein": "PTX3", "relationship_type": "biomarker", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Loeys-Dietz Syndrome", "glycan_involvement": "Glycosylation modulates PTX3's immune interactions.", "mechanism": "Elevated PTX3 levels reflect increased vascular inflammation in Loeys-Dietz syndrome.", "protein": "PTX3", "relationship_type": "biomarker", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Altered glycosylation may affect TIMP1's inhibitory activity.", "mechanism": "Elevated TIMP1 correlates with tumor progression and ECM remodeling.", "protein": "TIMP1", "relationship_type": "biomarker", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation may influence CXCL1's secretion and function.", "mechanism": "CXCL1 elevation is associated with tumor-associated inflammation.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction", "glycan_involvement": "Glycosylation impacts PTX3's plasma half-life and immune activity.", "mechanism": "PTX3 elevation marks acute vascular inflammation post-infarction.", "protein": "PTX3", "relationship_type": "biomarker", "source_pmcid": "PMC11843136" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "XO is glycosylated, affecting secretion and activity", "mechanism": "XO catalyzes uric acid synthesis, linking MAFLD and hyperuricemia", "protein": "Xanthine oxidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843138" }, { "confidence": "medium", "disease": "Urolithiasis", "glycan_involvement": "Glycosylation modulates XO activity and stability", "mechanism": "XO-driven hyperuricemia increases risk of uric acid stones", "protein": "Xanthine oxidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "MAFLD", "glycan_involvement": "Altered glycosylation may affect albumin half-life", "mechanism": "Serum albumin levels reflect liver synthetic function in MAFLD", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "MAFLD", "glycan_involvement": "Glycosylation patterns may shift in liver disease", "mechanism": "Serum globulin levels change with liver inflammation/fibrosis", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "MAFLD", "glycan_involvement": "Glycosylation affects GGT membrane localization", "mechanism": "Elevated GGT indicates liver dysfunction in MAFLD", "protein": "Gamma-glutamyl transpeptidase", "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "Urolithiasis", "glycan_involvement": "HDL glycoproteins modulate lipid transport", "mechanism": "Low HDL associated with increased kidney stone risk", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "MAFLD", "glycan_involvement": "LDL glycoproteins influence lipid metabolism", "mechanism": "Elevated LDL is a risk factor for MAFLD", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "low", "disease": "Urolithiasis", "glycan_involvement": "Glycosylation regulates platelet function", "mechanism": "Platelet count may reflect inflammation in stone disease", "protein": "Blood platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11843138" }, { "confidence": "medium", "disease": "Urolithiasis", "glycan_involvement": "Glycoproteins mediate lipid transport and metabolism", "mechanism": "High triglycerides independently increase stone risk", "protein": "Triglyceride-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11843138" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation affects XO secretion and activity", "mechanism": "XO activity drives uric acid production, leading to hyperuricemia", "protein": "Xanthine oxidase", "relationship_type": "causal", "source_pmcid": "PMC11843138" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for secretion and extracellular chaperone function.", "mechanism": "sCLU levels elevated in CSF/plasma; binds \u03b2-amyloid and may promote clearance, but also stabilizes phosphorylated Tau, contributing to plaque formation.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker/causal/protective", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation required for secretion and extracellular interactions.", "mechanism": "cCLU binds \u03b1-synuclein, inhibits aggregation and Lewy body formation; sCLU may inhibit astrocyte-mediated clearance, possibly worsening disease.", "protein": "Clusterin (CLU)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "N-glycosylation required for secretion and extracellular matrix interactions.", "mechanism": "CLU expression increases in kidney and urine during fibrosis; overexpression suppresses fibrosis progression.", "protein": "Clusterin (CLU)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "N-glycosylation enables extracellular chaperone activity.", "mechanism": "CLU inhibits TGF-\u03b2 signaling, reduces fibroblast activation and collagen deposition.", "protein": "Clusterin (CLU)", "relationship_type": "protective", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "CLU expression increases with fibrosis; inhibits TGF-\u03b2-mediated hepatic stellate cell activation and ECM deposition.", "protein": "Clusterin (CLU)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "high", "disease": "Diabetes/Insulin resistance", "glycan_involvement": "N-glycosylation required for secretion and receptor interaction.", "mechanism": "sCLU from adipocytes binds LRP2 on hepatocytes, inhibits insulin signaling, increases gluconeogenesis, reduces insulin sensitivity.", "protein": "Clusterin (CLU)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "high", "disease": "Atherosclerosis/Cardiovascular disease", "glycan_involvement": "N-glycosylation required for HDL association and function.", "mechanism": "CLU in HDL promotes cholesterol efflux, inhibits endothelial apoptosis; low CLU in HDL linked to disease.", "protein": "Clusterin (CLU)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation required for secretion and cardioprotective effect.", "mechanism": "sCLU decreases in plasma during early injury; exogenous CLU reduces infarct size and mortality.", "protein": "Clusterin (CLU)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation state determines subcellular localization and function.", "mechanism": "cCLU inhibits apoptosis and promotes autophagy in cancer cells; nCLU promotes apoptosis under stress.", "protein": "Clusterin (CLU)", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC11843140" }, { "confidence": "medium", "disease": "Osteoarthritis/Osteoporosis", "glycan_involvement": "N-glycosylation required for secretion and extracellular effects.", "mechanism": "CLU upregulated in OA/OP tissues; sCLU inhibits osteoblast differentiation and osteoclastogenesis, modulating bone metabolism.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843140" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "GPX3 is glycosylated for secretion and stability; glycosylation status not directly discussed.", "mechanism": "Promoter hypermethylation of GPX3 reduces antioxidant defense, increasing cisplatin resistance.", "protein": "GPX3", "protein_enriched": { "function": "Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione", "gene_name": "GPX3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22352" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "CHFR is glycosylated; glycosylation may affect nuclear localization but not directly discussed.", "mechanism": "Promoter hypermethylation silences CHFR, sensitizing cells to paclitaxel/docetaxel by disrupting mitotic checkpoint.", "protein": "CHFR", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensati", "gene_name": "CHFR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96EP1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "PAX5 is glycosylated; glycosylation may modulate transcriptional activity.", "mechanism": "Promoter methylation of PAX5 regulates GLUT1-mediated chemoresistance and p53 signaling, affecting cisplatin and docetaxel sensitivity.", "protein": "PAX5", "protein_enriched": { "function": "Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:10811620, PubMed:27181361). Fulfills a dual role by repressing B-lineage ina", "gene_name": "PAX5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02548" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "KLF4 glycosylation may affect DNA binding; not directly discussed.", "mechanism": "Promoter methylation of KLF4 predicts cisplatin sensitivity via apoptosis and cell cycle arrest.", "protein": "KLF4", "protein_enriched": { "function": "Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates th", "gene_name": "KLF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43474" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "REPRIMO is membrane glycoprotein; glycosylation may affect localization.", "mechanism": "Promoter hypermethylation impairs G2/M checkpoint, leading to cisplatin resistance.", "protein": "REPRIMO", "protein_enriched": { "function": "May be involved in the regulation of p53-dependent G2 arrest of the cell cycle. Seems to induce cell cycle arrest by inhibiting CDK1 activity and nuclear translocation of the CDC2 cyclin B1 complex (B", "gene_name": "RPRM", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q9NS64" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "FGF5 glycosylation required for secretion; not directly discussed.", "mechanism": "Low methylation of FGF5 correlates with poor response to chemoradiotherapy; unmethylated FGF5 supports cell survival.", "protein": "FGF5", "protein_enriched": { "function": "Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promo", "gene_name": "FGF5", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12034" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "GADD45\u03b1 is glycosylated; glycosylation may affect nuclear function.", "mechanism": "Promoter hypomethylation leads to overexpression, affecting cisplatin sensitivity via apoptosis disruption.", "protein": "GADD45\u03b1", "protein_enriched": { "function": "In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; ", "gene_name": "GADD45A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24522" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "OCT1 glycosylation may affect DNA binding; not directly discussed.", "mechanism": "Promoter methylation of OCT1 induced by cisplatin exposure causes resistance.", "protein": "OCT1", "protein_enriched": { "function": "Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immuno", "gene_name": "POU2F1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P14859" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "ABCB1 is a membrane glycoprotein; glycosylation critical for drug efflux function.", "mechanism": "Promoter demethylation and gene amplification of ABCB1 contribute to taxane resistance.", "protein": "ABCB1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843145" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "IGFBP7 is secreted glycoprotein; glycosylation affects stability and function.", "mechanism": "Lower promoter methylation correlates with increased globulin and reflux; role in ESCC progression.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843145" }, { "confidence": "high", "disease": "Gestational Hypertension (GH)", "glycan_involvement": "HSI includes glycoprotein liver enzymes (AST, ALT) as components.", "mechanism": "HSI reflects NAFLD status, which is associated with increased risk of GH via metabolic and inflammatory pathways.", "protein": "Hepatic Steatosis Index (HSI)", "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "high", "disease": "Preeclampsia (PE)", "glycan_involvement": "HSI includes glycoprotein liver enzymes (AST, ALT) as components.", "mechanism": "Elevated HSI predicts increased risk of PE, reflecting underlying NAFLD and metabolic dysfunction.", "protein": "Hepatic Steatosis Index (HSI)", "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Higher AST levels in early pregnancy are associated with increased risk of PE.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Gestational Hypertension (GH)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence its secretion and activity.", "mechanism": "Elevated ALT in early pregnancy is associated with increased risk of GH.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence its serum levels.", "mechanism": "Higher ALT levels are associated with increased risk of PE.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Gestational Hypertension (GH)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its function and serum stability.", "mechanism": "Elevated GGT in early pregnancy is associated with increased risk of GH.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its function and serum stability.", "mechanism": "Higher GGT levels are associated with increased risk of PE.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation modulates its secretion and activity.", "mechanism": "NAFLD-induced inflammation elevates IL-6, contributing to endothelial dysfunction and PE.", "protein": "Interleukin 6 (IL-6)", "relationship_type": "causal", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects its receptor binding and function.", "mechanism": "NAFLD increases TNF-\u03b1, promoting systemic inflammation and endothelial dysfunction in PE.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843148" }, { "confidence": "medium", "disease": "Preeclampsia (PE)", "glycan_involvement": "CCL2 is a glycoprotein; glycosylation influences its chemotactic activity.", "mechanism": "NAFLD elevates CCL2, contributing to inflammation and endothelial dysfunction in PE.", "protein": "C-C motif ligand 2 (CCL2)", "relationship_type": "causal", "source_pmcid": "PMC11843148" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects its cell surface expression.", "mechanism": "Upregulation via promoter hypomethylation enables immune evasion by inhibiting T cell activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "N-glycosylation required for VEGF secretion and receptor binding.", "mechanism": "Epigenetic upregulation (histone acetylation, DNA hypomethylation) promotes angiogenesis and tumor growth.", "protein": "VEGF", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "LUAD", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and signaling.", "mechanism": "Mutations and overexpression drive cell proliferation; epigenetic changes enhance pathway activation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11843169" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation affects MMP secretion and substrate specificity.", "mechanism": "Epigenetic activation in TME (via TGF-\u03b2) promotes ECM remodeling, invasion, and metastasis.", "protein": "MMPs", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11843169" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "O-glycosylation may affect stability and nuclear localization.", "mechanism": "Overexpression via mRNA upregulation and epigenetic activation sustains Wnt signaling, promoting proliferation.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Secreted glycoprotein; glycosylation required for function.", "mechanism": "Promoter hypermethylation silences SFRP1, lifting inhibition on Wnt pathway and promoting tumorigenesis.", "protein": "SFRP1", "protein_enriched": { "function": "Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell ", "gene_name": "SFRP1", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G58001LT", "G53434XO" ], "uniprot_id": "Q8N474" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Secreted glycoprotein; glycosylation required for Wnt inhibition.", "mechanism": "Promoter hypermethylation silences DKK1, leading to Wnt pathway activation and tumor progression.", "protein": "DKK1", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:220", "gene_name": "DKK1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "O94907" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Secreted glycoprotein; glycosylation required for Wnt binding.", "mechanism": "Promoter hypermethylation silences WIF1, resulting in Wnt pathway activation.", "protein": "WIF1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843169" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may affect APC stability and function.", "mechanism": "Promoter hypermethylation silences APC, disrupting \u03b2-catenin regulation and promoting tumorigenesis.", "protein": "APC", "protein_enriched": { "function": "Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity ", "gene_name": "APC", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60923RB", "G49108TO", "G80920RR", "G28905MY" ], "uniprot_id": "P25054" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "N-glycosylation essential for cell-cell adhesion function.", "mechanism": "Promoter hypermethylation silences CDH1, reducing cell adhesion and promoting metastasis.", "protein": "CDH1 (E-cadherin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11843169" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects trafficking and processing.", "mechanism": "Palmitoylation of APP promotes its cleavage by BACE1, increasing A\u03b2 production and plaque formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is glycosylated; glycosylation modulates stability and localization.", "mechanism": "Palmitoylation of BACE1 is essential for A\u03b2 generation; loss of palmitoylation reduces amyloid burden.", "protein": "BACE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843170" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "GPM6A is a glycoprotein; glycosylation may affect membrane localization.", "mechanism": "GPM6A palmitoylation influences brain development and is associated with depressive subtype of SCZ.", "protein": "GPM6A", "relationship_type": "biomarker", "source_pmcid": "PMC11843170" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "O-glycosylation at Gal-(\u03b2-1,3)-GalNAc; promotes aggregation.", "mechanism": "Glycosylation of MAP6 with Gal-(\u03b2-1,3)-GalNAc oligosaccharides leads to inclusion body formation and neuronal damage.", "protein": "MAP6", "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "PSD-95 is a glycoprotein; glycosylation may affect synaptic localization.", "mechanism": "Palmitoylation of PSD-95 is reduced in AD; restoration may protect synaptic integrity.", "protein": "PSD-95", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843170" }, { "confidence": "high", "disease": "Huntington's disease", "glycan_involvement": "GLT-1 is glycosylated; glycosylation affects transporter function.", "mechanism": "Reduced palmitoylation of GLT-1 impairs glutamate uptake, leading to excitotoxicity and neuronal death.", "protein": "GLT-1 (EAAT2)", "protein_enriched": { "function": "Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:15265858, PubMed:26690923, PubMed:7521911).", "gene_name": "SLC1A2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P43004" }, "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "high", "disease": "Intellectual disability", "glycan_involvement": "ZDHHC9 is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "Loss-of-function mutations in ZDHHC9 disrupt palmitoylation, causing X-linked intellectual disability.", "protein": "ZDHHC9", "protein_enriched": { "function": "Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth. Binds to double-stranded DNA and RNA. Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA. Binds ", "gene_name": "STRBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96SI9" }, "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "ZDHHC8 is glycosylated; glycosylation may affect localization.", "mechanism": "Increased ZDHHC8 expression correlates with seizure susceptibility; regulates palmitoylation of neuronal substrates.", "protein": "ZDHHC8", "protein_enriched": { "function": "Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (Probable). Through the palmitoylation o", "gene_name": "ZDHHC8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q9ULC8" }, "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "ZDHHC2 is glycosylated; glycosylation may modulate activity.", "mechanism": "Variants in ZDHHC2 increase risk of SCZ by altering palmitoylation of synaptic proteins.", "protein": "ZDHHC2", "protein_enriched": { "function": "Mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate/HCO3", "gene_name": "CA5B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59626AS" ], "uniprot_id": "Q9Y2D0" }, "relationship_type": "risk_factor", "source_pmcid": "PMC11843170" }, { "confidence": "medium", "disease": "Intellectual disability", "glycan_involvement": "ZDHHC15 is glycosylated; glycosylation may affect function.", "mechanism": "Disrupted ZDHHC15 expression due to X chromosome duplication leads to intellectual disability.", "protein": "ZDHHC15", "protein_enriched": { "function": "May regulate AMPA receptor content at nascent synapses, and have a role in postsynaptic development and maturation", "gene_name": "SYNDIG1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H7V2" }, "relationship_type": "causal", "source_pmcid": "PMC11843170" }, { "confidence": "high", "disease": "Moderate-to-severe pulmonary hypertension in ILD (Ms-PH)", "glycan_involvement": "Low galactosylation of IgG correlates with increased proinflammatory cytokines and PH severity.", "mechanism": "Elevated IgG levels are independently associated with Ms-PH, possibly reflecting systemic and local pulmonary artery inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Pulmonary hypertension associated with interstitial lung disease (PH-ILD)", "glycan_involvement": "Altered glycosylation (galactosylation) modulates inflammatory activity.", "mechanism": "IgG-mediated immune response and inflammation may promote PH development in ILD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Moderate-to-severe pulmonary hypertension in ILD (Ms-PH)", "glycan_involvement": "C4 is a glycoprotein; glycosylation is essential for its function.", "mechanism": "Lower C4 levels are associated with Ms-PH, suggesting complement activation and immune involvement.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Connective tissue disease-associated ILD (CTD-ILD)", "glycan_involvement": "Autoantibodies are glycoproteins; glycosylation affects immune recognition.", "mechanism": "Higher anti-U1RNP antibody positivity correlates with PH severity in CTD-ILD.", "protein": "Anti-U1 ribonucleoprotein (U1RNP) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Connective tissue disease-associated ILD (CTD-ILD)", "glycan_involvement": "Glycosylation state influences IgG's proinflammatory properties.", "mechanism": "Elevated IgG levels reflect ongoing immune activation in CTD-ILD, which may predispose to PH.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Connective tissue disease-associated ILD (CTD-ILD)", "glycan_involvement": "Glycosylation required for complement activation and function.", "mechanism": "Reduced C4 levels indicate complement consumption in immune-mediated lung disease.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "low", "disease": "Pulmonary hypertension associated with interstitial lung disease (PH-ILD)", "glycan_involvement": "Targeting galactosylation of IgG could alter disease course.", "mechanism": "Modulation of IgG glycosylation may reduce inflammation and PH progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843187" }, { "confidence": "low", "disease": "Pulmonary hypertension associated with interstitial lung disease (PH-ILD)", "glycan_involvement": "Glycosylation affects complement-mediated immune responses.", "mechanism": "Complement activation may contribute to vascular injury and PH.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "causal", "source_pmcid": "PMC11843187" }, { "confidence": "low", "disease": "Moderate-to-severe pulmonary hypertension in ILD (Ms-PH)", "glycan_involvement": "Glycosylation may affect antibody pathogenicity.", "mechanism": "Anti-U1RNP antibody positivity is associated with increased risk of Ms-PH in CTD-ILD.", "protein": "Anti-U1 ribonucleoprotein (U1RNP) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11843187" }, { "confidence": "medium", "disease": "Moderate-to-severe pulmonary hypertension in ILD (Ms-PH)", "glycan_involvement": "Low galactosylation enhances proinflammatory activity.", "mechanism": "Proinflammatory IgG glycoforms may drive vascular inflammation and remodeling.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843187" }, { "confidence": "high", "disease": "Cancer (multiple types)", "glycan_involvement": "Not directly specified; glycosylation may affect membrane localization and function.", "mechanism": "Activates MAPK, EGFR, Wnt, TGF-\u03b2, and NF-\u03baB pathways to promote tumor proliferation, migration, invasion.", "protein": "TMEM16A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Pulmonary artery hypertension", "glycan_involvement": "Not specified.", "mechanism": "Upregulation in PASMCs promotes vascular remodeling via ERK/AKT activation.", "protein": "TMEM16A", "relationship_type": "causal", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Cancer (breast, liver, ovarian, renal)", "glycan_involvement": "Not specified; likely impacts trafficking and stability.", "mechanism": "Overexpression induces chemoresistance, proliferation, EMT, and inflammatory response via TGF-\u03b2 and Wnt pathways.", "protein": "TMEM45A", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Cancer (gastric, breast, colon)", "glycan_involvement": "Not specified.", "mechanism": "Promotes proliferation, migration, invasion via AKT, Wnt/\u03b2-catenin, and GSK-3\u03b2/\u03b2-catenin signaling.", "protein": "TMEM97", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Cancer (NSCLC, breast, ovarian)", "glycan_involvement": "Not specified.", "mechanism": "Enhances invasion/metastasis via Wnt/Dishevelled pathway; associated with platinum resistance.", "protein": "TMEM88", "protein_enriched": { "function": "Involved in the negative regulation of lymphocyte motility. It mediates the migration-inhibitory effects of IL6. Serves as a positive regulator of the RhoA signaling pathway. Enhancement of RhoA activ", "gene_name": "GCSAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N6F7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Neurodegenerative diseases (FTLD, AD)", "glycan_involvement": "Not specified; glycosylation may affect aggregation propensity.", "mechanism": "SNPs and protein aggregation linked to dementia, FTLD, and AD risk.", "protein": "TMEM106B", "protein_enriched": { "function": "Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the", "gene_name": "MGAT4A", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9UM21" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Polycystic kidney disease", "glycan_involvement": "Not specified; ciliary glycosylation may be relevant.", "mechanism": "Mutations disrupt ciliary function, activate JNK/ERK/mTOR pathways, leading to cyst formation.", "protein": "TMEM67 (Meckelin)", "protein_enriched": { "function": "Required for ciliary structure and function. Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involve", "gene_name": "TMEM67", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G83460ZZ" ], "uniprot_id": "Q5HYA8" }, "relationship_type": "causal", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Podocytopathy (FSGS, minimal change disease)", "glycan_involvement": "Not specified.", "mechanism": "Maintains podocyte viability and glomerular filtration barrier; downregulation leads to injury and proteinuria.", "protein": "TMEM63C", "protein_enriched": { "function": "Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes", "gene_name": "BMPER", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q8N8U9" }, "relationship_type": "protective", "source_pmcid": "PMC11843188" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Upregulation promotes proliferation; knockdown slows tumor growth.", "protein": "TMEM22", "protein_enriched": { "function": "Phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:25231987). Phosphatidylserine is a specific marker only present at the surface of a", "gene_name": "XKR8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6D3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Podocytopathy (FSGS, minimal change disease)", "glycan_involvement": "Not specified; may affect protein folding and trafficking.", "mechanism": "Loss in podocytes causes ER stress, foot process effacement, proteinuria, and glomerulosclerosis.", "protein": "TMEM30A", "relationship_type": "causal", "source_pmcid": "PMC11843188" }, { "confidence": "high", "disease": "Familial cholestasis", "glycan_involvement": "Not directly described; possible glycosylation may affect protein stability or localization.", "mechanism": "Mutation in ZFYVE19 disrupts ciliary function in cholangiocytes, leading to cholestasis.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "causal", "source_pmcid": "PMC11843454" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Not specified.", "mechanism": "Chronic cholestasis due to ZFYVE19 mutation progresses to cirrhosis.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "causal", "source_pmcid": "PMC11843454" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Not specified.", "mechanism": "Portal vein dysplasia and fibrosis secondary to ZFYVE19 mutation.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "causal", "source_pmcid": "PMC11843454" }, { "confidence": "high", "disease": "Familial cholestasis", "glycan_involvement": "Glycosylation affects ALP stability and serum half-life.", "mechanism": "Elevated ALP is a biochemical marker of cholestasis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843454" }, { "confidence": "high", "disease": "Familial cholestasis", "glycan_involvement": "Glycosylation required for GGT activity and secretion.", "mechanism": "Elevated GGT is a marker of cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843454" }, { "confidence": "medium", "disease": "Wilson\u2019s disease (excluded in this case)", "glycan_involvement": "Glycosylation required for ceruloplasmin secretion.", "mechanism": "Low ceruloplasmin suggests Wilson\u2019s disease, but not causal here.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC11843454" }, { "confidence": "medium", "disease": "Pruritus", "glycan_involvement": "Not specified.", "mechanism": "Cholestasis due to ZFYVE19 mutation leads to pruritus.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "causal", "source_pmcid": "PMC11843454" }, { "confidence": "medium", "disease": "Familial cholestasis", "glycan_involvement": "Not specified.", "mechanism": "Gene therapy targeting ZFYVE19 may reverse cholestatic pathology.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843454" }, { "confidence": "high", "disease": "Familial cholestasis", "glycan_involvement": "Not specified.", "mechanism": "UDCA improves cholestasis in ZFYVE19 mutation patients.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843454" }, { "confidence": "medium", "disease": "Familial cholestasis", "glycan_involvement": "Not specified.", "mechanism": "Odevixibat reduces pruritus in cholestasis.", "protein": "ZFYVE19 (ANCHR)", "protein_enriched": { "function": "", "gene_name": "C1orf52", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N6N3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11843454" }, { "confidence": "high", "disease": "Light chain deposition disease (LCDD)", "glycan_involvement": "Light chains are glycoproteins; glycosylation may affect aggregation and deposition.", "mechanism": "Monoclonal light chains deposit in kidney basement membranes, causing renal dysfunction.", "protein": "Immunoglobulin light chain", "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "high", "disease": "Heavy chain deposition disease (HCDD)", "glycan_involvement": "Heavy chains are glycoproteins; glycosylation may influence tissue deposition.", "mechanism": "Monoclonal heavy chains deposit in renal tissues, leading to kidney injury.", "protein": "Immunoglobulin heavy chain", "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "high", "disease": "Proliferative glomerulonephritis with monoclonal immune deposits (PGNMID)", "glycan_involvement": "IgG glycosylation can modulate immune complex formation and deposition.", "mechanism": "Monoclonal IgG deposits in glomeruli trigger inflammation and proliferation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "Anti-glomerular basement membrane disease", "glycan_involvement": "IgM is highly glycosylated; glycan structures may affect deposition.", "mechanism": "Monoclonal IgM deposits in glomerular basement membrane, contributing to pathology.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "Light chain proximal tubulopathy (LCPT)", "glycan_involvement": "Glycosylation may influence light chain aggregation and toxicity.", "mechanism": "Monoclonal light chains accumulate in proximal tubules, causing dysfunction.", "protein": "Immunoglobulin light chain", "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "Cryoglobulinemic glomerulonephritis", "glycan_involvement": "Glycosylation affects solubility and precipitation of IgG.", "mechanism": "Monoclonal IgG forms cryoprecipitates that deposit in glomeruli.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "Immunotactoid glomerulopathy", "glycan_involvement": "Glycan modifications may influence microtubule formation.", "mechanism": "Monoclonal IgG forms microtubular deposits in glomeruli.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "C3 glomerulonephritis (C3GN)", "glycan_involvement": "C3 is glycosylated; glycosylation may affect complement activation.", "mechanism": "Monoclonal immunoglobulins may dysregulate complement, leading to C3 deposition.", "protein": "C3 complement protein", "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "low", "disease": "Membranous nephropathy", "glycan_involvement": "IgG glycosylation can affect immune complex formation.", "mechanism": "Monoclonal IgG deposits in glomerular basement membrane, causing nephropathy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11843701" }, { "confidence": "high", "disease": "Monoclonal gammopathy of renal significance (MGRS)", "glycan_involvement": "Glycosylation status may influence detection and pathogenicity.", "mechanism": "Monoclonal light chains in serum/urine are diagnostic for MGRS.", "protein": "Immunoglobulin light chain", "relationship_type": "biomarker", "source_pmcid": "PMC11843701" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "N-glycosylation modulates IL-6 stability and secretion.", "mechanism": "Pro-inflammatory cytokine elevated in asthma, contributing to airway inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "medium", "disease": "Chronic Bronchitis", "glycan_involvement": "N-glycosylation affects TNF-\u03b1 receptor binding and signaling.", "mechanism": "Promotes chronic airway inflammation and tissue damage.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Drives airway inflammation and hyperresponsiveness.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation essential for multimerization and function.", "mechanism": "Levels inversely related to obesity; modulates inflammation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844003" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation required for proper folding and receptor interaction.", "mechanism": "Hyperinsulinemia in obesity affects airway smooth muscle contractility.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "medium", "disease": "Chronic Bronchitis", "glycan_involvement": "N-glycosylation modulates bioactivity.", "mechanism": "Elevated IL-6 promotes chronic inflammation in bronchitis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "O-glycosylation critical for function.", "mechanism": "Anti-inflammatory effects may reduce airway inflammation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. 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It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC11844003" }, { "confidence": "high", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Altered N-glycosylation due to mannose metabolism dysregulation.", "mechanism": "Disruption of fructose/mannose metabolism affects glycoprotein synthesis, contributing to FPHL pathogenesis.", "protein": "Mannose-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Reduced N-glycosylation in keratinocytes.", "mechanism": "Impaired glucose metabolism reduces glycoprotein synthesis in hair follicle cells, leading to hair loss.", "protein": "Glucose-modified glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Decreased glycosylation affects keratinocyte viability.", "mechanism": "Glucose deficiency in ORS keratinocytes impairs glycoprotein function, contributing to hair follicle miniaturization.", "protein": "Outer root sheath (ORS) keratinocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Insulin Resistance (IR)", "glycan_involvement": "Altered glycosylation impacts insulin signaling.", "mechanism": "Mannose metabolism dysregulation is linked to IR, which increases FPHL risk.", "protein": "Mannose-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "N-glycosylation changes in reproductive tissues.", "mechanism": "Glycoprotein synthesis disruption via mannose metabolism is associated with PCOS and FPHL comorbidity.", "protein": "Mannose-containing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Oxidative stress may impair glycosylation machinery.", "mechanism": "Elevated CSSG indicates oxidative stress, inhibiting glycoprotein function in hair follicle morphogenesis.", "protein": "Cysteine-glutathione disulfide (CSSG)", "relationship_type": "causal", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Modulation of N-glycosylation as a therapeutic strategy.", "mechanism": "Targeting mannose metabolism may restore glycoprotein synthesis and hair growth.", "protein": "Mannose-containing glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Glycosylation profile changes detectable in serum.", "mechanism": "Altered glycoprotein glycosylation reflects metabolic status and FPHL risk.", "protein": "Glucose-modified glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "Enhancing glycosylation improves keratinocyte function.", "mechanism": "Restoring glycoprotein glycosylation in ORS keratinocytes may prevent hair follicle miniaturization.", "protein": "Outer root sheath (ORS) keratinocyte glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11844202" }, { "confidence": "medium", "disease": "Female Pattern Hair Loss (FPHL)", "glycan_involvement": "N-glycosylation patterns measurable in blood.", "mechanism": "Serum mannose levels and glycoprotein glycosylation status serve as early indicators of FPHL risk.", "protein": "Mannose-containing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11844202" }, { "confidence": "high", "disease": "Anti-NMDAR encephalitis (NMDAR-E)", "glycan_involvement": "IgG glycosylation modulates immune effector functions and CNS inflammation.", "mechanism": "CSF-specific oligoclonal IgG bands indicate intrathecal B-cell activation and are associated with disease severity and poor prognosis.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Anti-LGI1 encephalitis (LGI1-E)", "glycan_involvement": "IgG glycosylation affects antibody-mediated neuroinflammation.", "mechanism": "CSF-specific OCBs predict poor prognosis and increased disease severity.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Anti-GABABR encephalitis (GABABR-E)", "glycan_involvement": "Glycosylation of IgG influences CNS immune response.", "mechanism": "CSF-specific OCBs are independent risk factors for poor outcome.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Anti-NMDAR encephalitis (NMDAR-E)", "glycan_involvement": "NMDAR glycosylation is essential for receptor surface expression and antibody recognition.", "mechanism": "Autoantibodies target NMDAR glycoprotein, leading to receptor dysfunction and encephalitis.", "protein": "NMDAR", "relationship_type": "causal", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Anti-LGI1 encephalitis (LGI1-E)", "glycan_involvement": "LGI1 glycosylation affects secretion and antibody binding.", "mechanism": "Autoantibodies target LGI1 glycoprotein, disrupting synaptic function.", "protein": "LGI1", "protein_enriched": { "function": "", "gene_name": "C1orf74", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96LT6" }, "relationship_type": "causal", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Anti-GABABR encephalitis (GABABR-E)", "glycan_involvement": "GABABR glycosylation is required for proper folding and cell surface localization.", "mechanism": "Autoantibodies bind GABABR glycoprotein, impairing inhibitory neurotransmission.", "protein": "GABABR", "relationship_type": "causal", "source_pmcid": "PMC11844203" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IgG glycosylation modulates pathogenicity in MS.", "mechanism": "CSF-specific OCBs are diagnostic and prognostic markers in MS.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "medium", "disease": "Anti-MOG antibody-associated disease (MOGAD)", "glycan_involvement": "MOG glycosylation affects antigenicity and immune recognition.", "mechanism": "OCB positivity is more frequent in females and may indicate increased relapse risk.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 glycosylation influences antibody binding.", "mechanism": "AQP4 antibodies are diagnostic; glycosylation may affect antigen presentation.", "protein": "AQP4", "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "medium", "disease": "Viral encephalitis (VE)", "glycan_involvement": "IgG glycosylation may modulate antiviral immune responses.", "mechanism": "CSF-specific OCBs are less frequent and not predictive of severity in VE compared to NSAE.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844203" }, { "confidence": "low", "disease": "AEPVM", "glycan_involvement": "Glycosylation of spike protein may influence immunogenicity and cross-reactivity.", "mechanism": "Autoantibodies against spike glycoprotein may cross-react with RPE glycoproteins, triggering immune-mediated retinal damage.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC11844306" }, { "confidence": "high", "disease": "Best disease (Bestrophinopathy)", "glycan_involvement": "Glycosylation may affect protein folding and function.", "mechanism": "Mutations in bestrophin-1 glycoprotein cause vitelliform lesions similar to those seen in AEPVM.", "protein": "Bestrophin-1", "protein_enriched": { "function": "Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+) (PubMed:11904445, PubMed:12907679, PubMed:18179881, PubMed:18400985, PubMed:1985323", "gene_name": "BEST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O76090" }, "relationship_type": "causal", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "AEPVM", "glycan_involvement": "Altered glycosylation may affect antigenicity and immune recognition.", "mechanism": "Immune-mediated attack on RPE glycoproteins may lead to serous retinal detachment and vitelliform deposits.", "protein": "Retinal pigment epithelium (RPE) glycoproteins", "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC11844306" }, { "confidence": "high", "disease": "Choroidal Neovascularization (CNV)", "glycan_involvement": "VEGF glycosylation affects receptor binding and angiogenic activity.", "mechanism": "Anti-VEGF therapy may be used to treat CNV, a complication of AEPVM.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "AEPVM", "glycan_involvement": "Glycosylation status may help differentiate disease forms.", "mechanism": "Genetic testing for bestrophin-1 distinguishes AEPVM from Best disease.", "protein": "Bestrophin-1", "protein_enriched": { "function": "Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+) (PubMed:11904445, PubMed:12907679, PubMed:18179881, PubMed:18400985, PubMed:1985323", "gene_name": "BEST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O76090" }, "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC11844306" }, { "confidence": "low", "disease": "COVID-19 vaccine-induced immune response", "glycan_involvement": "Spike glycoprotein glycosylation modulates immune response.", "mechanism": "Vaccination may induce autoantibodies against spike glycoprotein, potentially triggering retinal autoimmunity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "Paraneoplastic syndromes", "glycan_involvement": "Aberrant glycosylation may increase antigenicity.", "mechanism": "Paraneoplastic autoantibodies may target RPE glycoproteins, leading to AEPVM-like retinal changes.", "protein": "Retinal pigment epithelium (RPE) glycoproteins", "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "Choroidal Neovascularization (CNV)", "glycan_involvement": "Glycosylation may affect protein stability and retinal integrity.", "mechanism": "Bestrophinopathy may predispose to CNV formation.", "protein": "Bestrophin-1", "protein_enriched": { "function": "Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+) (PubMed:11904445, PubMed:12907679, PubMed:18179881, PubMed:18400985, PubMed:1985323", "gene_name": "BEST1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O76090" }, "relationship_type": "causal (complication)", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "Best disease (Bestrophinopathy)", "glycan_involvement": "Glycosylation status may be diagnostic.", "mechanism": "RPE glycoprotein dysfunction is a feature of Best disease, helping distinguish it from AEPVM.", "protein": "Retinal pigment epithelium (RPE) glycoproteins", "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC11844306" }, { "confidence": "medium", "disease": "AEPVM", "glycan_involvement": "VEGF glycosylation influences therapeutic efficacy.", "mechanism": "Anti-VEGF agents may be considered if CNV develops in AEPVM.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target (complication)", "source_pmcid": "PMC11844306" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation affects APOE stability and function in lipid transport and immune modulation.", "mechanism": "APOE is overexpressed in HCC, correlates with favorable prognosis, impacts immune cell infiltration, DNA methylation, and is an independent prognostic indicator.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker/therapeutic_target/protective", "source_pmcid": "PMC11844312" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation modulates APOE isoform function and clearance.", "mechanism": "APOE genotype is a major genetic risk factor for late-onset AD, influencing amyloid deposition and neuroinflammation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "medium", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "Glycosylation may affect receptor binding and immune modulation.", "mechanism": "APOE binds LILRB4 receptor, suppresses T-cell responses, and promotes immune evasion.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11844312" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation influences APOE's lipid transport and anti-tumor activity.", "mechanism": "APOE inhibits tumor cell proliferation and migration by modulating cholesterol metabolism.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11844312" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may regulate APOE-LRP1 interaction.", "mechanism": "Elevated APOE mRNA is associated with poor prognosis and promotes cell migration/invasion via LRP1 binding.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11844312" }, { "confidence": "low", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may affect APOE localization and function.", "mechanism": "Nuclear APOE expression in peritoneal fluid correlates with prognosis.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "low", "disease": "Lung adenocarcinoma", "glycan_involvement": "N-glycosylation modulates APOE stability and activity.", "mechanism": "APOE promotes cell proliferation and migration; higher expression linked to aggressive disease.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may regulate exosomal sorting and intercellular transfer.", "mechanism": "High APOE expression is associated with shortened survival and muscle damage; exosome-mediated transfer from macrophages enhances tumor cell migration.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "low", "disease": "Brain tumors", "glycan_involvement": "N-glycosylation affects APOE's role in the CNS.", "mechanism": "APOE is implicated in tumor progression and immune modulation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation status may influence APOE's tumor-promoting activity.", "mechanism": "APOE is overexpressed and may contribute to tumorigenesis.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC11844312" }, { "confidence": "high", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect stability and half-life.", "mechanism": "Hypoalbuminemia is independently associated with increased mortality in COPD, reflecting inflammation and malnutrition.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may modulate albumin's vascular and osmotic functions.", "mechanism": "Low serum albumin predicts adverse outcomes in heart failure.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Idiopathic pulmonary hypertension", "glycan_involvement": "Glycosylation status may influence albumin's role in vascular permeability.", "mechanism": "BAR (BUN/albumin ratio) predicts severity and prognosis.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Acute pulmonary embolism", "glycan_involvement": "Glycosylation may affect albumin's anti-inflammatory properties.", "mechanism": "BAR is a prognostic factor for mortality.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Aspiration pneumonia", "glycan_involvement": "Glycosylation may influence albumin's immune-modulatory effects.", "mechanism": "BAR predicts poor outcomes.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Community-acquired pneumonia", "glycan_involvement": "Glycosylation may affect albumin's interaction with immune cells.", "mechanism": "BAR accurately predicts severity.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus with chronic kidney disease", "glycan_involvement": "Glycosylation may impact renal clearance and albuminuria.", "mechanism": "BAR correlates with lower 90-day survival rate.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "IgG Fc glycosylation modulates immune response and inflammation.", "mechanism": "Low total serum IgG levels are associated with poor prognosis in COPD.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "Cell surface glycoproteins mediate eosinophil adhesion and migration.", "mechanism": "Elevated blood eosinophil count is associated with poor prognosis in COPD.", "protein": "Blood eosinophil", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "medium", "disease": "Gastrointestinal bleeding", "glycan_involvement": "Glycosylation may affect albumin's protective role in vascular integrity.", "mechanism": "BAR is associated with adverse outcomes.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC11844315" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor interaction.", "mechanism": "Lower TSH levels are associated with increased NAFLD risk in euthyroid adults.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "FT3 is derived from thyroglobulin, a glycoprotein; glycosylation affects hormone release.", "mechanism": "Elevated FT3 levels are associated with increased NAFLD risk and progression.", "protein": "Free triiodothyronine (FT3)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "FT4 is derived from thyroglobulin, a glycoprotein; glycosylation affects hormone release.", "mechanism": "Elevated FT4 levels are associated with increased NAFLD risk.", "protein": "Free thyroxine (FT4)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TSH glycosylation modulates its activity and half-life.", "mechanism": "Higher TSH levels within normal range are associated with advanced fibrosis in NAFLD.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "FT3 derived from glycoprotein precursor; glycosylation affects hormone bioavailability.", "mechanism": "Higher FT3/FT4 ratio correlates with increased severity of liver fibrosis.", "protein": "Free triiodothyronine (FT3)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Albumin glycosylation status can affect its function and clearance.", "mechanism": "Lower albumin levels are included in fibrosis scoring; reflects liver synthetic dysfunction.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate interactions and clearance.", "mechanism": "Lower platelet count is a marker of advanced fibrosis.", "protein": "Platelet (PLT)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT is a marker of hepatocyte injury in NAFLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "Elevated AST is used in fibrosis scoring (APRI, FIB-4).", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "TSH glycosylation affects receptor binding and metabolic regulation.", "mechanism": "Impaired central sensitivity to thyroid hormones (higher TFQI, TSHI) is associated with obesity risk.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11844316" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Includes glycoprotein enzymes (AST, ALT) whose glycosylation may affect serum levels.", "mechanism": "FIB-4 score (includes glycoprotein markers) is elevated in NAFLD, especially with diabetes, indicating advanced fibrosis.", "protein": "FIB-4", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Includes AST, a glycoprotein enzyme; glycosylation may modulate activity.", "mechanism": "BARD score is higher in diabetic NAFLD, reflecting increased fibrosis risk.", "protein": "BARD score", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Includes albumin, a glycoprotein; glycosylation status may affect function.", "mechanism": "NFS is significantly higher in diabetic NAFLD, indicating advanced fibrosis.", "protein": "NAFLD fibrosis score (NFS)", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Glycosylation may influence serum stability and detection.", "mechanism": "Serum AST is altered in NASH and differs between diabetic and non-diabetic patients.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Glycosylation may influence serum stability and detection.", "mechanism": "Serum ALT is altered in NASH and differs between diabetic and non-diabetic patients.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis may affect function and clearance.", "mechanism": "Serum albumin is used in fibrosis scoring; hypoalbuminemia reflects advanced liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Platelet surface glycoproteins are altered in liver disease.", "mechanism": "Low platelet count is a marker of advanced fibrosis/cirrhosis in NAFLD/NASH.", "protein": "Platelet (PLT)", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Depends on glycoprotein markers (AST, ALT, PLT).", "mechanism": "High FIB-4 score predicts cirrhosis risk in NAFLD/NASH, especially with diabetes.", "protein": "FIB-4", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Depends on glycoprotein markers (AST, ALT, PLT).", "mechanism": "High FIB-4 score is associated with increased HCC risk in advanced NAFLD/NASH.", "protein": "FIB-4", "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation changes in metabolic syndrome may affect albumin function.", "mechanism": "Albumin is a component of NFS, reflecting liver synthetic function in metabolic syndrome.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11844969" }, { "confidence": "high", "disease": "Insulin Autoimmune Syndrome (IAS)", "glycan_involvement": "IAAs are glycosylated immunoglobulins; glycosylation affects antibody function and clearance.", "mechanism": "High-titer IAAs bind endogenous insulin, forming immune complexes that disrupt insulin action, causing hypoglycemia and glycemic fluctuations.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "causal", "source_pmcid": "PMC11845856" }, { "confidence": "high", "disease": "Insulin Autoimmune Syndrome (IAS)", "glycan_involvement": "Insulin is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "Endogenous insulin is sequestered by IAAs, leading to abnormal insulin: C-peptide ratios and hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11845856" }, { "confidence": "high", "disease": "Exogenous Insulin Autoimmune Syndrome (EIAS)", "glycan_involvement": "IAAs are glycosylated; glycosylation may modulate immune complex formation.", "mechanism": "IAAs induced by exogenous insulin bind insulin, causing insulin resistance, hyperglycemia, or hypoglycemia.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "causal", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Type B Insulin Resistance Syndrome", "glycan_involvement": "Receptor glycosylation affects antibody binding and receptor function.", "mechanism": "Autoantibodies against insulin receptor (glycoprotein) cause receptor dysfunction, leading to insulin resistance or hypoglycemia.", "protein": "Insulin Receptor", "relationship_type": "causal", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Graves' Disease", "glycan_involvement": "IAAs are glycosylated; altered glycosylation may affect disease association.", "mechanism": "IAS frequently co-occurs with Graves' disease; IAAs are present in both.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "biomarker/association", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Hashimoto's Thyroiditis", "glycan_involvement": "IAAs are glycosylated; glycosylation may influence immune response.", "mechanism": "IAS is associated with Hashimoto's; IAAs are detected in these patients.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "biomarker/association", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "IAAs are glycosylated; glycosylation may modulate autoimmunity.", "mechanism": "IAS is reported in SLE patients; IAAs are present.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "biomarker/association", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Monoclonal IAAs are glycosylated; glycosylation may affect pathogenicity.", "mechanism": "IAS can occur in multiple myeloma; monoclonal IAAs may be produced.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "biomarker/association", "source_pmcid": "PMC11845856" }, { "confidence": "medium", "disease": "Monoclonal Gammopathy", "glycan_involvement": "Monoclonal IAAs are glycosylated; glycosylation may affect immune complex formation.", "mechanism": "IAS is associated with monoclonal gammopathy; monoclonal IAAs detected.", "protein": "Insulin Autoantibody (IAA)", "relationship_type": "biomarker/association", "source_pmcid": "PMC11845856" }, { "confidence": "high", "disease": "Insulin Autoimmune Syndrome (IAS)", "glycan_involvement": "IgG glycosylation modulates antibody function and immune complex clearance.", "mechanism": "IgG is the predominant IAA isotype in IAS, mediating insulin binding and hypoglycemia.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11845856" }, { "confidence": "high", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation of nephrin modulates immune recognition and podocyte function.", "mechanism": "Circulating anti-nephrin antibodies cause podocyte injury and foot process effacement.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "Potential O-glycosylation may affect membrane association and actin interaction.", "mechanism": "Increased MYO1B abundance in adult MCD glomeruli reflects actin cytoskeleton remodeling in response to immune injury.", "protein": "MYO1B", "protein_enriched": { "function": "Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, whi", "gene_name": "MYO16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6X6" }, "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Focal Segmental Glomerulosclerosis (FSGS)", "glycan_involvement": "N-glycosylation regulates VTN matrix interactions.", "mechanism": "Elevated VTN in adult FSGS glomeruli indicates increased extracellular matrix deposition and glomerulosclerosis.", "protein": "VTN (Vitronectin)", "protein_enriched": { "function": "Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-II", "gene_name": "SERPIND1", "glycan_count": 66, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G53434XO", "G29068FM", "G00875VP", "G00912UN", "G02030ZB", "G04854VP", "G05933EN", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G10846ZT", "G22572EH", "G24954UD", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G31986NC", "G37881RL", "G40574BA", "G40834TG", "G43669FQ", "G45395BF", "G45504EY", "G47518TP", "G48414YA", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G78790NZ", "G82830MN", "G83646BJ", "G90093AU", "G94470IW", "G95865ZB", "G49108TO", "G57321FI", "G11314AS", "G11629QQ", "G13694XX", "G15169WU", "G22310AV", "G41247ZX", "G42358LZ", "G43223CG", "G47644PP", "G47737VJ", "G52527GH", "G56518TU", "G57776ZS", "G59324HL", "G75983OB", "G76868JS", "G80075MS", "G86880BF", "G88374WZ", "G94917XT", "G98611JV" ], "uniprot_id": "P05546" }, "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Focal Segmental Glomerulosclerosis (FSGS)", "glycan_involvement": "Glycosylation affects collagen IV assembly and stability.", "mechanism": "Increased COL4A1 in adult FSGS glomeruli reflects basement membrane thickening and sclerosis.", "protein": "COL4A1", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation modulates fibrinogen function and immune interactions.", "mechanism": "Higher abundance of FGA in adult MCD glomeruli suggests activation of coagulation pathways.", "protein": "FGA", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation affects fibrinogen beta chain stability.", "mechanism": "Elevated FGB in adult MCD glomeruli is linked to immune and coagulation pathway activation.", "protein": "FGB", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in", "gene_name": "FGB", "glycan_count": 124, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G81399MY", "G00912UN", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G09197ZW", "G10486CT", "G10846ZT", "G11314AS", "G11911BT", "G12745LE", "G13131HA", "G14994KB", "G15038BD", "G15664MX", "G18647XP", "G20706XG", "G22572EH", "G22768VO", "G23505EP", "G23863VK", "G25079LO", "G25418HZ", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G31916IQ", "G31986NC", "G34989PA", "G35029YA", "G35253PZ", "G36191CD", "G37399XV", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47448YK", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G49018RC", "G49642SA", "G49955PK", "G50045TK", "G50073PQ", "G50282JC", "G54010QB", "G54600FO", "G55383ZG", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G60923RB", "G61256FT", "G62765YT", "G63980BQ", "G70441OD", "G70619PT", "G71146HJ", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G75850OP", "G75983OB", "G77547TA", "G80920RR", "G82463GQ", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G87051GH", "G87389XI", "G89098OM", "G90659AW", "G91365ZQ", "G92050GC", "G92551JA", "G94470IW", "G95865ZB", "G17015OC", "G49108TO" ], "uniprot_id": "P02675" }, "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation influences fibrinogen gamma chain function.", "mechanism": "Increased FGG in adult MCD glomeruli reflects immune system involvement.", "protein": "FGG", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation modulates APCS immune interactions.", "mechanism": "Higher APCS in adult MCD glomeruli indicates immune activation.", "protein": "APCS", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Focal Segmental Glomerulosclerosis (FSGS)", "glycan_involvement": "N-glycosylation critical for immunoglobulin stability and antigen binding.", "mechanism": "Elevated IGKV1-5 in FSGS glomeruli suggests increased adaptive immune activity.", "protein": "IGKV1-5", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "medium", "disease": "Minimal Change Disease (MCD)", "glycan_involvement": "N-glycosylation essential for immunoglobulin function.", "mechanism": "Increased IGKC in adult MCD tubulointerstitium reflects immune system involvement.", "protein": "IGKC", "relationship_type": "biomarker", "source_pmcid": "PMC11845903" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects insulin stability and bioavailability in oral formulations.", "mechanism": "Oral delivery of insulin via PCBBA nanocarriers lowers blood glucose in type 1 diabetic mice.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846306" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates insulin absorption and protection from degradation.", "mechanism": "PCBBA nanocarriers enhance oral insulin delivery, improving glycemic control in type 2 diabetic mice.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846306" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect UCP-1 stability and function in adipose tissue.", "mechanism": "PCBBA upregulates UCP-1 expression, promoting WAT browning and increased energy expenditure, reducing obesity.", "protein": "UCP-1", "relationship_type": "protective", "source_pmcid": "PMC11846306" }, { "confidence": "high", "disease": "Adipose Tissue Inflammation", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 in WAT drives inflammation and insulin resistance; PCBBA reduces TNF-\u03b1 expression.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11846306" }, { "confidence": "high", "disease": "Adipose Tissue Inflammation", "glycan_involvement": "Glycosylation affects IL-1\u03b2 maturation and release.", "mechanism": "IL-1\u03b2 promotes inflammatory macrophage polarization in WAT; PCBBA lowers IL-1\u03b2 levels.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11846306" }, { "confidence": "medium", "disease": "Liver Inflammation", "glycan_involvement": "Glycosylation modulates IL-6 stability and signaling.", "mechanism": "IL-6 is elevated in hepatic inflammation; PCBBA reduces IL-6 expression in liver tissue.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11846306" }, { "confidence": "medium", "disease": "Hepatic Steatosis (Fatty Liver Disease)", "glycan_involvement": "Glycosylation regulates FASN activity and localization.", "mechanism": "FASN drives hepatic lipid accumulation; PCBBA downregulates FASN, reducing steatosis.", "protein": "FASN", "relationship_type": "causal", "source_pmcid": "PMC11846306" }, { "confidence": "medium", "disease": "Adipose Tissue Inflammation", "glycan_involvement": "Glycosylation affects CD11c cell surface expression and immune interactions.", "mechanism": "CD11c marks M1-like pro-inflammatory macrophages; PCBBA reduces CD11c+ macrophages in WAT.", "protein": "CD11c", "protein_enriched": { "function": "Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antige", "gene_name": "FCER2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P06734" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846306" }, { "confidence": "low", "disease": "Hepatic Steatosis (Fatty Liver Disease)", "glycan_involvement": "Glycosylation modulates SREBP1c processing and activity.", "mechanism": "SREBP1c regulates hepatic lipid synthesis; PCBBA stabilizes SREBP1c expression, contributing to improved metabolism.", "protein": "SREBP1c", "relationship_type": "causal", "source_pmcid": "PMC11846306" }, { "confidence": "low", "disease": "Hepatic Steatosis (Fatty Liver Disease)", "glycan_involvement": "Glycosylation may influence PPAR\u03b1 nuclear localization and function.", "mechanism": "PPAR\u03b1 promotes fatty acid oxidation; PCBBA maintains PPAR\u03b1 expression, supporting liver metabolic health.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC11846306" }, { "confidence": "high", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "Lower galactosylation/sialylation, higher fucosylation; FA2, FA2[3]G1, FA2BG2S2 glycan traits", "mechanism": "Decreased galactosylation and sialylation of IgG N-glycans are associated with axSpA diagnosis and disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "high", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "FA2 N-glycan positively correlates with ASDAS-CRP, SPARCC-SIJ, SPARCC-spine scores", "mechanism": "Increased abundance of FA2 (asialylated, afucosylated di-antennary glycan) correlates with higher disease activity in axSpA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "high", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "Lower FA2BG2S2 abundance in axSpA vs SLE, RA, OA, gout", "mechanism": "Decreased FA2BG2S2 (fucosylated, bisected, digalactosylated, disialylated glycan) is a unique marker distinguishing axSpA from other rheumatic diseases.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "high", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "Lower FA2[3]G1 abundance in axSpA, SLE, RA, OA, gout compared to controls", "mechanism": "Decreased FA2[3]G1 (mono-galactosylated glycan) is a shared trait among all studied rheumatic diseases, including axSpA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered N-glycan abundances in SLE vs controls", "mechanism": "Decreased FA2[3]G1, A2BG2, FA2G2S2 and increased FA2BG2S2 are associated with SLE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Altered N-glycan abundances in RA vs controls", "mechanism": "Increased M5, FA2BG2S2 and decreased FA2[3]G1, FA2G2 are associated with RA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Lower FA2[3]G1 abundance in OA vs controls", "mechanism": "Decreased FA2[3]G1 is associated with OA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Lower FA2[3]G1 and FA2G2 abundance in gout vs controls", "mechanism": "Decreased FA2[3]G1 and FA2G2 are associated with gout.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "medium", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "Lower sialylation (e.g., FA2BG2S2) linked to higher IL-23, TNF\u03b1, and inflammation", "mechanism": "IL-23/Th17 axis and TNF\u03b1 may drive pro-inflammatory state in axSpA by reducing IgG sialylation via downregulation of St6Gal1 glycosyltransferase.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11846342" }, { "confidence": "high", "disease": "Axial spondyloarthritis (axSpA)", "glycan_involvement": "Glycan-cytokine correlation supports biomarker potential", "mechanism": "IgG N-glycan patterns (FA2, FA2[3]G1, FA2BG2S2) show canonical correlation with inflammatory cytokines (IL-23, TNF\u03b1, ESR) in axSpA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846342" }, { "confidence": "high", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "Not specified in article; CK may be glycosylated, but glycosylation not discussed.", "mechanism": "Elevated CK levels indicate muscle damage and disease activity in IIM.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "medium", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "Not specified; AST may be glycosylated, but not discussed.", "mechanism": "Elevated AST reflects muscle injury in IIM.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "medium", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "Not specified; ALT may be glycosylated, but not discussed.", "mechanism": "Elevated ALT can indicate muscle or liver involvement in IIM.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Dermatomyositis", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in dermatomyositis.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Antisynthetase syndrome", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in antisynthetase syndrome.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Polymyositis", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in polymyositis.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Necrotizing myopathy", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in necrotizing myopathy.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Overlap myositis", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in overlap myositis.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Interstitial myositis", "glycan_involvement": "Not specified.", "mechanism": "CK elevation is used to monitor muscle damage in interstitial myositis.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "medium", "disease": "Dermatomyositis", "glycan_involvement": "Not specified.", "mechanism": "AST elevation can reflect muscle injury in dermatomyositis.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC11846393" }, { "confidence": "high", "disease": "Carbapenem-resistant Klebsiella pneumoniae infection", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "\u03b2-lactamase enzymes hydrolyze carbapenems, conferring resistance.", "protein": "\u03b2-lactamase enzymes", "relationship_type": "causal", "source_pmcid": "PMC11846486" }, { "confidence": "high", "disease": "Carbapenem-resistant Klebsiella pneumoniae infection", "glycan_involvement": "Avibactam mimics glycan structures to bind \u03b2-lactamase active sites.", "mechanism": "Avibactam inhibits \u03b2-lactamase enzymes, restoring ceftazidime efficacy.", "protein": "Avibactam", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846486" }, { "confidence": "high", "disease": "Carbapenem-resistant Klebsiella pneumoniae infection", "glycan_involvement": "Indirect; cell wall synthesis involves glycan structures.", "mechanism": "Ceftazidime targets bacterial cell wall synthesis; efficacy restored by avibactam.", "protein": "Ceftazidime", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Complicated intra-abdominal infection", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "\u03b2-lactamase-mediated resistance in pathogens causing intra-abdominal infection.", "protein": "\u03b2-lactamase enzymes", "relationship_type": "causal", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Complicated urinary tract infection", "glycan_involvement": "Glycosylation may affect enzyme secretion.", "mechanism": "\u03b2-lactamase enzymes confer resistance in urinary tract pathogens.", "protein": "\u03b2-lactamase enzymes", "relationship_type": "causal", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Hospital-acquired pneumonia", "glycan_involvement": "Glycosylation may influence enzyme localization.", "mechanism": "\u03b2-lactamase enzymes contribute to resistance in pneumonia-causing bacteria.", "protein": "\u03b2-lactamase enzymes", "relationship_type": "causal", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Bacteremia", "glycan_involvement": "Glycosylation may affect enzyme stability in circulation.", "mechanism": "\u03b2-lactamase enzymes enable bloodstream infection persistence.", "protein": "\u03b2-lactamase enzymes", "relationship_type": "causal", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Complicated intra-abdominal infection", "glycan_involvement": "Mimics glycan interactions at enzyme active site.", "mechanism": "Avibactam inhibits \u03b2-lactamase, allowing ceftazidime to treat infection.", "protein": "Avibactam", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Complicated urinary tract infection", "glycan_involvement": "Mimics glycan interactions at enzyme active site.", "mechanism": "Avibactam restores ceftazidime activity against resistant pathogens.", "protein": "Avibactam", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846486" }, { "confidence": "medium", "disease": "Hospital-acquired pneumonia", "glycan_involvement": "Mimics glycan interactions at enzyme active site.", "mechanism": "Avibactam enables ceftazidime efficacy in pneumonia with resistant bacteria.", "protein": "Avibactam", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846486" }, { "confidence": "high", "disease": "Human granulocytic anaplasmosis (HGA)", "glycan_involvement": "Glycosylation of bacterial surface proteins facilitates host cell interaction and immune evasion.", "mechanism": "Bacterial glycoproteins mediate entry and survival in neutrophils, evading host immune response.", "protein": "Anaplasma phagocytophilum surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11846626" }, { "confidence": "high", "disease": "Human granulocytic anaplasmosis (HGA)", "glycan_involvement": "Host glycoproteins in neutrophil membranes are manipulated by bacterial effectors.", "mechanism": "Anaplasma infects neutrophils, altering glycoprotein-rich vacuoles to evade autophagy and lysosome fusion.", "protein": "Neutrophil glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11846626" }, { "confidence": "medium", "disease": "Stroke (cerebral infarction)", "glycan_involvement": "Endothelial glycoproteins may be targeted or altered during infection, affecting vascular integrity.", "mechanism": "Hypothesized infection of endothelial cells by Anaplasma may contribute to vascular injury and stroke.", "protein": "Endothelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11846626" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Factor V is a glycoprotein; glycosylation affects its stability and function in coagulation.", "mechanism": "Tick-borne infections (e.g., Rickettsia) increase Factor V, promoting procoagulant activity.", "protein": "Factor V", "relationship_type": "biomarker", "source_pmcid": "PMC11846626" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Antithrombin glycosylation is critical for its anticoagulant activity.", "mechanism": "Decreased antithrombin levels in tick-borne infections contribute to coagulopathy.", "protein": "Antithrombin", "relationship_type": "biomarker", "source_pmcid": "PMC11846626" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Factor VIII glycosylation is essential for secretion and function.", "mechanism": "Altered plasma Factor VIII activity in tick-borne infections affects coagulation balance.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC11846626" }, { "confidence": "high", "disease": "Lyme disease", "glycan_involvement": "IgM is heavily glycosylated, affecting antigen recognition and immune response.", "mechanism": "IgM detected by Western Blot indicates early Lyme disease or possible co-infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846626" }, { "confidence": "high", "disease": "Lyme disease", "glycan_involvement": "IgG glycosylation modulates effector functions and immune clearance.", "mechanism": "IgG serology used to confirm Lyme disease; negative in early infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11846626" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Altered glycoprotein signaling in neutrophils may contribute to HLH pathogenesis.", "mechanism": "Anaplasma infection of neutrophils can trigger HLH via immune dysregulation.", "protein": "Neutrophil glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11846626" }, { "confidence": "low", "disease": "Meningitis", "glycan_involvement": "Glycosylation may aid in crossing blood-brain barrier.", "mechanism": "Rare neurological manifestation; bacterial glycoproteins may facilitate CNS entry.", "protein": "Anaplasma phagocytophilum surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11846626" }, { "confidence": "high", "disease": "Anti-tuberculosis drug-induced liver injury (DILI)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated GGT indicates cholestasis and impaired biliary excretion, correlating with increased DILI risk.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Anti-tuberculosis drug-induced liver injury (DILI)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation influences half-life and function.", "mechanism": "Low albumin reflects impaired hepatic synthetic function and higher DILI risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "medium", "disease": "Anti-tuberculosis drug-induced liver injury (DILI)", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates its activity and serum detection.", "mechanism": "Elevated ALP may indicate cholestatic injury in DILI.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Glycosylation affects GGT secretion and serum levels.", "mechanism": "GGT elevation is associated with chronic liver disease and fibrosis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Altered glycosylation may affect albumin clearance in liver disease.", "mechanism": "Decreased albumin is a marker of chronic liver dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Anti-tuberculosis drug-induced liver injury (DILI)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its serum stability.", "mechanism": "Elevated AST reflects hepatocellular injury and predicts DILI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Anti-tuberculosis drug-induced liver injury (DILI)", "glycan_involvement": "ALT is glycosylated; glycan modifications may influence its serum levels.", "mechanism": "Elevated ALT is a sensitive marker of hepatocellular injury and DILI risk.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation modulates GGT function in fibrotic liver.", "mechanism": "High GGT correlates with advanced fibrosis/cirrhosis and impaired detoxification.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Altered glycosylation patterns in cirrhosis may affect albumin function.", "mechanism": "Low albumin indicates advanced fibrosis/cirrhosis and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation affects ALP isoform distribution in liver disease.", "mechanism": "Elevated ALP may reflect cholestasis in advanced fibrosis/cirrhosis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846638" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans, modulating cell adhesion and immune responses.", "mechanism": "Serum galectin-3 levels are higher in T2D patients; associated with inflammation, fibrosis, and \u03b2-cell damage.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycan binding influences endothelial cell proliferation and monocyte/macrophage chemoattraction.", "mechanism": "Galectin-3 correlates with ASCVD risk score, but not independently predictive in regression analysis.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Lectin activity affects vascular remodeling via glycan interactions.", "mechanism": "Meta-analysis shows galectin-3 as a risk factor; inverse relationship in hepatic steatosis patients.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycan binding modulates cardiac fibrosis and remodeling.", "mechanism": "Galectin-3 is a reliable biomarker for atrial fibrillation.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Obstructive Sleep Apnea", "glycan_involvement": "Glycan interactions may influence inflammatory pathways in sleep apnea.", "mechanism": "Galectin-3 is a reliable biomarker for obstructive sleep apnea.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "FGF-23 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "FGF-23 levels do not differ between T2D and controls in this study; previous studies show conflicting results.", "protein": "Fibroblast Growth Factor 23 (FGF-23)", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation modulates FGF-23's endocrine and paracrine effects.", "mechanism": "FGF-23 correlates with ASCVD risk score, but not independently predictive.", "protein": "Fibroblast Growth Factor 23 (FGF-23)", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation required for FGF-23 secretion and activity.", "mechanism": "FGF-23 predicts adverse CV outcomes in CAD and T2D patients, but not in those without T2D.", "protein": "Fibroblast Growth Factor 23 (FGF-23)", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "low", "disease": "Hepatic Steatosis", "glycan_involvement": "Glycan binding may modulate hepatic inflammation and fibrosis.", "mechanism": "Inverse relationship between galectin-3 and CAD severity in hepatic steatosis patients.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC11846640" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Lectin-glycan interactions mediate cell death and immune responses.", "mechanism": "Galectin-3 overexpression enhances oxidative stress and \u03b2-cell apoptosis, affecting glucose metabolism.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC11846640" }, { "confidence": "high", "disease": "Myocardial damage in severe pneumonia (children)", "glycan_involvement": "Hyaluronic acid is a glycosaminoglycan; its interaction with glycoproteins is central to ECM remodeling.", "mechanism": "Elevated serum hyaluronic acid reflects increased inflammation and extracellular matrix turnover associated with myocardial injury.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "high", "disease": "Myocardial damage in severe pneumonia (children)", "glycan_involvement": "Procollagen III is glycosylated, affecting secretion and ECM assembly.", "mechanism": "Elevated levels indicate increased collagen synthesis and myocardial fibrosis during injury.", "protein": "Procollagen III N-terminal propeptide", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "high", "disease": "Myocardial damage in severe pneumonia (children)", "glycan_involvement": "sST2 is N-glycosylated, which affects its stability and secretion.", "mechanism": "sST2 is released in response to cardiac stress and inflammation, correlating with myocardial injury severity.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "high", "disease": "Myocardial damage in severe pneumonia (children)", "glycan_involvement": "NT-proBNP is glycosylated, influencing its plasma half-life and detection.", "mechanism": "Elevated NT-proBNP reflects cardiac dysfunction and stress.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "high", "disease": "Myocardial damage in severe pneumonia (children)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Increased cfDNA indicates cell death and tissue injury, including myocardial cells.", "protein": "cfDNA", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "N-glycosylation modulates sST2 secretion and function.", "mechanism": "sST2 is a prognostic marker for heart failure due to its role in cardiac stress signaling.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation is required for proper folding and secretion.", "mechanism": "Reflects active collagen synthesis and fibrotic remodeling.", "protein": "Procollagen III N-terminal propeptide", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Acts as a glycosaminoglycan in ECM, interacting with glycoproteins.", "mechanism": "High levels indicate ongoing inflammatory response and ECM turnover.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects NT-proBNP stability and detection.", "mechanism": "Elevated NT-proBNP is a standard marker for cardiac dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "No direct glycan involvement.", "mechanism": "cfDNA is released during cell death and is a marker of tissue injury and inflammation.", "protein": "cfDNA", "relationship_type": "biomarker", "source_pmcid": "PMC11846653" }, { "confidence": "high", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "AChR is a glycoprotein; glycosylation affects receptor stability and immune recognition.", "mechanism": "Autoantibodies bind AChR, causing receptor internalization, functional blockade, and complement-mediated destruction at the neuromuscular junction.", "protein": "Acetylcholine Receptor (AChR)", "protein_enriched": { "function": "Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane", "gene_name": "CHRNA1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G09724ZC", "G22573RC", "G22768VO", "G34499SX", "G55220VL", "G63337SS", "G68668TB" ], "uniprot_id": "P02708" }, "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "high", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "MuSK is glycosylated; glycosylation may influence antibody binding and receptor function.", "mechanism": "Anti-MuSK antibodies disrupt MuSK signaling, impairing NMJ maintenance and leading to muscle weakness.", "protein": "Muscle-Specific Kinase (MuSK)", "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "LRP4 is a glycoprotein; glycosylation may modulate ligand and antibody interactions.", "mechanism": "Anti-LRP4 antibodies interfere with agrin-LRP4-MuSK signaling, impairing NMJ formation.", "protein": "Low-density lipoprotein receptor-related protein 4 (LRP4)", "protein_enriched": { "function": "Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spi", "gene_name": "FARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y4F1" }, "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "Agrin is heavily glycosylated; glycosylation is critical for its function at the NMJ.", "mechanism": "Autoantibodies to agrin disrupt NMJ signaling, contributing to MG pathogenesis.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "high", "disease": "Refractory Myasthenia Gravis", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding and B-cell depletion efficacy.", "mechanism": "Targeted by rituximab to deplete B-cells, reducing autoantibody production and disease activity.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Refractory Myasthenia Gravis", "glycan_involvement": "CD19 is glycosylated; glycosylation may influence detection and function.", "mechanism": "CD19 levels are used to monitor B-cell depletion after rituximab therapy.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846680" }, { "confidence": "high", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "C5 is a glycoprotein; glycosylation is important for complement activation.", "mechanism": "Cleavage of C5 leads to MAC formation and postsynaptic membrane damage in AChR-positive MG.", "protein": "Complement C5", "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Myasthenia Gravis (MG)", "glycan_involvement": "MAC components are glycoproteins; glycosylation affects assembly and function.", "mechanism": "MAC formation causes lysis of the postsynaptic membrane, leading to neuromuscular transmission failure.", "protein": "Membrane Attack Complex (MAC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Thymomatous Myasthenia Gravis", "glycan_involvement": "Glycosylation may affect antigenicity and immune response.", "mechanism": "AChR antibodies are more common in thymomatous MG and guide diagnosis and management.", "protein": "Acetylcholine Receptor (AChR)", "protein_enriched": { "function": "Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane", "gene_name": "CHRNA1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G09724ZC", "G22573RC", "G22768VO", "G34499SX", "G55220VL", "G63337SS", "G68668TB" ], "uniprot_id": "P02708" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846680" }, { "confidence": "medium", "disease": "Refractory Myasthenia Gravis", "glycan_involvement": "Glycosylation may influence antibody binding and clinical phenotype.", "mechanism": "MuSK antibody positivity predicts rapid and robust response to rituximab.", "protein": "Muscle-Specific Kinase (MuSK)", "relationship_type": "biomarker", "source_pmcid": "PMC11846680" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation of mucins (core 1 structure)", "mechanism": "Reduced C1GALT2 expression leads to decreased synthesis of core 1 type mucin, impairing mucosal barrier", "protein": "C1GALT2", "relationship_type": "causal", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "O-glycosylation defect in mucins", "mechanism": "Decreased C1GALT2 expression observed in both piglet model and human IBD patients", "protein": "C1GALT2", "relationship_type": "biomarker", "source_pmcid": "PMC11846933" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Initiation of O-glycosylation on mucins", "mechanism": "Loss of GALNT1 reduces O-glycan initiation on mucins, weakening mucus defense", "protein": "GALNT1", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:8690719, P", "gene_name": "GALNT1", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G70441OD", "G08918WF", "G27058EU", "G45395BF", "G49108TO" ], "uniprot_id": "Q10472" }, "relationship_type": "causal", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "O-glycosylation of mucins", "mechanism": "Reduced GALNT1 and O-glycans in UC patient gut and DLY piglets", "protein": "GALNT1", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:8690719, P", "gene_name": "GALNT1", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G70441OD", "G08918WF", "G27058EU", "G45395BF", "G49108TO" ], "uniprot_id": "Q10472" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846933" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Regulation of O-glycosylation genes", "mechanism": "KMT2C downregulation leads to reduced O-glycosylation gene expression, compromising barrier", "protein": "KMT2C", "relationship_type": "causal", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "N-glycan core fucosylation", "mechanism": "Higher FUT8 expression (fucosylation) increases mucin anti-infection ability", "protein": "FUT8", "relationship_type": "protective", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Post-weaning diarrhea", "glycan_involvement": "O-glycosylation of secreted mucin", "mechanism": "Increased MUC2 expression reflects mucosal stress response to injury/diarrhea", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "O-glycosylation of secreted mucin", "mechanism": "Upregulated MUC5AC in DLY piglets indicates mucosal stress/inflammation", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC11846933" }, { "confidence": "low", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-GlcNAc modification of proteins", "mechanism": "Downregulation of OGT may affect O-GlcNAcylation, impacting mucosal signaling and barrier", "protein": "OGT", "relationship_type": "causal", "source_pmcid": "PMC11846933" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "O-glycosylation defect", "mechanism": "Decreased C1GALT2 and core 1 mucin in UC patients and DLY piglets", "protein": "C1GALT2", "relationship_type": "biomarker", "source_pmcid": "PMC11846933" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N- and O-glycosylation modulate protein binding and activity.", "mechanism": "Bypasses FVIII deficiency by activating FX via platelet-dependent and TF-dependent pathways.", "protein": "Eptacog alfa (rFVIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Distinct N-glycan profile increases platelet and EPCR binding.", "mechanism": "Bypasses FVIII deficiency; increased platelet and EPCR binding enhances hemostatic efficacy.", "protein": "Eptacog beta (rFVIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "Glycosylation affects protein interactions.", "mechanism": "Bypasses FIX deficiency by activating FX on platelets and via TF.", "protein": "Eptacog alfa (rFVIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "High-mannose and hybrid N-glycans increase binding.", "mechanism": "Bypasses FIX deficiency; enhanced platelet and EPCR binding improves efficacy.", "protein": "Eptacog beta (rFVIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "EPCR glycosylation mediates ligand binding.", "mechanism": "Binding of rFVIIa to EPCR impairs protein C activation, reducing anticoagulant activity and promoting hemostasis.", "protein": "Endothelial Protein C Receptor (EPCR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "Gla domain and glycosylation required for EPCR binding.", "mechanism": "Normally downregulates thrombin generation; displacement by rFVIIa reduces anticoagulant effect.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC11847032" }, { "confidence": "medium", "disease": "Hemarthrosis", "glycan_involvement": "N-glycans may affect tissue retention.", "mechanism": "EPCR-mediated endocytosis and tissue redistribution may provide extended joint protection.", "protein": "Eptacog beta (rFVIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847032" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Not directly implicated.", "mechanism": "High-dose or sequential use increases thrombotic risk.", "protein": "Eptacog alfa (rFVIIa)", "relationship_type": "causal", "source_pmcid": "PMC11847032" }, { "confidence": "low", "disease": "Thrombosis", "glycan_involvement": "Distinct glycosylation may affect safety.", "mechanism": "No reported cases; glycan profile may reduce risk.", "protein": "Eptacog beta (rFVIIa)", "relationship_type": "causal", "source_pmcid": "PMC11847032" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may modulate EPCR/PAR-1 interactions.", "mechanism": "Anti-inflammatory and barrier-protective effects via EPCR/PAR-1 signaling may reduce vascular inflammation.", "protein": "Eptacog beta (rFVIIa)", "relationship_type": "protective", "source_pmcid": "PMC11847032" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "HBsAg is heavily glycosylated, affecting immune recognition and viral infectivity.", "mechanism": "HBsAg presence in serum indicates active HBV infection and is used for diagnosis and monitoring.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Occult HBV infection", "glycan_involvement": "HBcAg glycosylation modulates immune response.", "mechanism": "Anti-HBc antibody positivity without HBsAg indicates occult HBV infection.", "protein": "Hepatitis B core antigen (HBcAg)", "relationship_type": "biomarker", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation of HBeAg affects secretion and immune modulation.", "mechanism": "HBeAg positivity indicates active viral replication and higher infectivity.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "E2 is highly glycosylated, shielding epitopes from neutralizing antibodies.", "mechanism": "E2 mediates viral entry and immune evasion, contributing to chronic infection.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "causal", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Dense glycan shield on gp120 impairs antibody recognition.", "mechanism": "gp120 mediates viral entry into host cells and immune evasion.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation may influence carcinogenesis and immune escape.", "mechanism": "Chronic HBsAg positivity is a major risk factor for progression to hepatocellular carcinoma.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Immunoglobulin glycosylation affects antibody function and half-life.", "mechanism": "Presence of anti-HBs antibody confers immunity and protection against HBV infection.", "protein": "Anti-HBs antibody", "relationship_type": "protective", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Occult HBV infection", "glycan_involvement": "Immunoglobulin glycosylation modulates immune response.", "mechanism": "Anti-HBc antibody is used to detect past or occult HBV infection.", "protein": "Anti-HBc antibody", "relationship_type": "biomarker", "source_pmcid": "PMC11847036" }, { "confidence": "medium", "disease": "Hepatitis D virus co-infection", "glycan_involvement": "HDVAg glycosylation may affect immune recognition.", "mechanism": "HDVAg positivity indicates HDV co-infection, which worsens HBV disease outcome.", "protein": "Hepatitis D antigen (HDVAg)", "relationship_type": "biomarker", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Vaccine efficacy depends on glycosylation status of HBsAg.", "mechanism": "HBsAg is targeted by HBV vaccines to induce protective immunity.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847036" }, { "confidence": "high", "disease": "Endothelial cell senescence", "glycan_involvement": "O-GlcNAcylation and UFMylation increase YAP stability", "mechanism": "YAP is upregulated in senescent endothelial cells and promotes senescence via nuclear localization and activation of senescence markers.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "Cardiovascular aging", "glycan_involvement": "UFMylation stabilizes YAP, enhancing its pro-aging effects", "mechanism": "YAP promotes endothelial cell senescence, leading to vascular aging and dysfunction.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of adhesion molecules facilitates their function", "mechanism": "YAP induces secretion of adhesion molecules (VCAM-1, ICAM-1, E-selectin), promoting vascular inflammation and atherosclerosis.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "O-GlcNAcylation increases YAP stability", "mechanism": "YAP regulates COX-2/mPGES-1 expression; reduced autophagic degradation of YAP increases hypertension risk.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "medium", "disease": "Arterial stiffness", "glycan_involvement": "UFMylation increases YAP nuclear localization", "mechanism": "YAP activation promotes TGF-\u03b2/Smad signaling, leading to arterial stiffness.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "Endothelial cell senescence", "glycan_involvement": "UFMylation is a ubiquitin-like modification, not classical glycosylation but functionally similar", "mechanism": "UFMylation of YAP increases its stability and nuclear localization, promoting EC senescence.", "protein": "UFM1-modified YAP", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "Vascular inflammation", "glycan_involvement": "VCAM-1 is a glycoprotein; glycosylation is essential for its function", "mechanism": "VCAM-1 is upregulated by YAP in senescent ECs, facilitating leukocyte adhesion and inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "Cardiovascular aging", "glycan_involvement": "Targets UFMylation, a ubiquitin-like modification", "mechanism": "Compound 8.5 inhibits UFMylation of YAP, promoting its degradation and reducing EC senescence and vascular aging.", "protein": "Compound 8.5 (inhibits UFMylation)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847039" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "UFMylation is a ubiquitin-like modification", "mechanism": "UFMylation mediates ER stress response, providing protection in heart failure models.", "protein": "UFM1", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBT9" }, "relationship_type": "protective", "source_pmcid": "PMC11847039" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "UFMylation is a ubiquitin-like modification", "mechanism": "UFMylation of PD-L1 increases its stability, promoting tumor immune evasion.", "protein": "UFMylation of PD-L1", "relationship_type": "causal", "source_pmcid": "PMC11847039" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "eNOS is a glycoprotein; glycosylation may affect its stability and localization, influencing metabolic regulation.", "mechanism": "eNOS deficiency leads to increased hepatic fat, insulin resistance, and obesity, promoting MASLD progression.", "protein": "Endothelial Nitric Oxide Synthase (eNOS)", "relationship_type": "causal", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated; glycosylation may affect its secretion and stability as a biomarker.", "mechanism": "Elevated AST activity correlates with liver damage and MASLD progression.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT glycosylation may modulate its release and detection in plasma.", "mechanism": "ALT activity increases with liver injury in MASLD, especially in advanced stages.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Lipoproteins are glycosylated; glycan patterns affect lipid transport and disease risk.", "mechanism": "Higher serum cholesterol is associated with MASLD severity, especially in males.", "protein": "Serum Cholesterol (LDL/HDL carriers)", "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation of apolipoproteins influences lipoprotein metabolism and disease risk.", "mechanism": "Elevated plasma triglycerides are linked to MASLD progression.", "protein": "Triglyceride-rich Lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation may regulate eNOS activity and metabolic effects.", "mechanism": "eNOS deficiency promotes visceral fat accumulation and obesity.", "protein": "Endothelial Nitric Oxide Synthase (eNOS)", "relationship_type": "causal", "source_pmcid": "PMC11847041" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect eNOS function in glucose metabolism.", "mechanism": "eNOS knockout mice develop insulin resistance, a key feature of type 2 diabetes.", "protein": "Endothelial Nitric Oxide Synthase (eNOS)", "relationship_type": "causal", "source_pmcid": "PMC11847041" }, { "confidence": "medium", "disease": "Cardiac Dysfunction", "glycan_involvement": "Glycosylation may impact eNOS localization in endothelial cells.", "mechanism": "eNOS deficiency contributes to cardiovascular dysfunction in metabolic syndrome.", "protein": "Endothelial Nitric Oxide Synthase (eNOS)", "relationship_type": "causal", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect AST plasma levels.", "mechanism": "AST elevation is a marker of liver injury in NAFLD.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation may modulate ALT stability and detection.", "mechanism": "ALT elevation reflects hepatocellular damage in NAFLD.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11847041" }, { "confidence": "high", "disease": "Familial hypercholesterolemia", "glycan_involvement": "Glycosylation affects PCSK9 secretion and stability.", "mechanism": "PCSK9 regulates LDL receptor degradation; gene editing reduces cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease", "glycan_involvement": "Glycosylation modulates ANGPTL3 activity.", "mechanism": "ANGPTL3 modulates lipid metabolism; gene editing lowers triglycerides.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Transthyretin amyloidosis", "glycan_involvement": "Glycosylation influences TTR stability and aggregation.", "mechanism": "TTR aggregation causes amyloidosis; gene editing reduces TTR levels.", "protein": "TTR (Transthyretin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Hereditary angioedema", "glycan_involvement": "Glycosylation affects KLKB1 secretion and activity.", "mechanism": "KLKB1 involved in bradykinin production; gene editing reduces angioedema attacks.", "protein": "KLKB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Hyper-IgM syndrome", "glycan_involvement": "Glycosylation required for CD40LG function and cell surface expression.", "mechanism": "CD40LG deficiency impairs immunoglobulin class switching.", "protein": "CD40LG", "relationship_type": "causal", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Severe combined immunodeficiency (SCID)", "glycan_involvement": "Glycosylation necessary for IL2RG receptor stability.", "mechanism": "IL2RG mutations cause defective cytokine signaling.", "protein": "IL2RG", "relationship_type": "causal", "source_pmcid": "PMC11847086" }, { "confidence": "medium", "disease": "Artemis deficiency", "glycan_involvement": "Glycosylation may affect Artemis nuclear localization.", "mechanism": "Artemis mutations impair DNA repair in lymphocytes.", "protein": "Artemis (DCLRE1C)", "protein_enriched": { "function": "Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination (PubMed:11336668, PubMed:11955432, PubMed:12055248, PubMed:14744996, PubMed:", "gene_name": "DCLRE1C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96SD1" }, "relationship_type": "causal", "source_pmcid": "PMC11847086" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation modulates PARP-1 activity.", "mechanism": "PARP-1 involved in DNA repair; gene editing increases chemosensitivity.", "protein": "PARP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Glycosylation affects dystrophin stability and muscle membrane association.", "mechanism": "Dystrophin deficiency leads to muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "Liver-targeted gene therapy", "glycan_involvement": "Recognizes terminal galactose/N-acetylgalactosamine on glycoproteins.", "mechanism": "ASGR1 mediates uptake of GalNAc-modified therapeutics in hepatocytes.", "protein": "ASGR1", "protein_enriched": { "function": "Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-ace", "gene_name": "ASGR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P07306" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847086" }, { "confidence": "high", "disease": "B-cell ALL", "glycan_involvement": "CD19 is a glycoprotein; glycosylation affects cell surface expression and antibody binding.", "mechanism": "Targeted by blinatumomab and CAR-T therapies for B-cell ALL.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847096" }, { "confidence": "high", "disease": "B-cell ALL", "glycan_involvement": "CD22 glycosylation modulates antibody-drug conjugate binding and internalization.", "mechanism": "Targeted by inotuzumab ozogamicin for B-cell ALL.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847096" }, { "confidence": "high", "disease": "B-cell ALL", "glycan_involvement": "CD20 glycosylation influences rituximab binding and efficacy.", "mechanism": "Rituximab is used in CD20+ B-cell ALL patients.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847096" }, { "confidence": "high", "disease": "ALL", "glycan_involvement": "BCL-2 is glycosylated; glycosylation may affect stability and drug interaction.", "mechanism": "Venetoclax inhibits BCL-2, promoting apoptosis in ALL blasts.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847096" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "MCL-1 glycosylation may regulate protein turnover and apoptosis resistance.", "mechanism": "High MCL-1 expression predicts resistance to venetoclax-based therapy.", "protein": "MCL-1", "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "BCL-XL glycosylation may affect anti-apoptotic function.", "mechanism": "Elevated BCL-XL expression associated with lack of response to venetoclax.", "protein": "BCL-XL", "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "CD34 glycosylation is critical for cell adhesion and migration.", "mechanism": "CD34+ blast expansion observed in nonresponders to venetoclax therapy.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "HLA-DR glycosylation affects antigen presentation and immune recognition.", "mechanism": "HLA-DR+ blast populations expanded in resistant ALL cases.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "CD38 glycosylation modulates enzymatic activity and antibody binding.", "mechanism": "CD38+ blast populations associated with disease progression.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "low", "disease": "ALL", "glycan_involvement": "TdT glycosylation may affect nuclear localization and activity.", "mechanism": "TdT+ blast populations mark immature lymphoid cells in ALL.", "protein": "TdT", "relationship_type": "biomarker", "source_pmcid": "PMC11847096" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "SLC7A11 is a glycoprotein; glycosylation may affect its stability and cell surface expression, but not directly studied here.", "mechanism": "SLC7A11 upregulation in inflammatory macrophages inhibits ferroptosis, promoting fibrosis; GAMG downregulates SLC7A11 to induce ferroptosis and reduce fibrosis.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847116" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "IRF1 is a glycoprotein; glycosylation may modulate its nuclear localization, but not directly addressed.", "mechanism": "GAMG increases IRF1, which represses SLC7A11 transcription, promoting ferroptosis in inflammatory macrophages and alleviating fibrosis.", "protein": "IRF1", "protein_enriched": { "function": "Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060,", "gene_name": "IRF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10914" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847116" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen I is N-glycosylated, which affects its secretion and assembly in ECM.", "mechanism": "Collagen I accumulation marks fibrosis; GAMG reduces its deposition.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "\u03b1-SMA can be O-glycosylated, influencing filament assembly.", "mechanism": "\u03b1-SMA upregulation indicates hepatic stellate cell activation and fibrosis; reduced by GAMG.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "GPX4 is a glycoprotein; glycosylation may affect its stability.", "mechanism": "GPX4 is a ferroptosis regulator; no significant change with GAMG, but its activity is essential for macrophage survival.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "ACSL4 is a glycoprotein; glycosylation may affect its function.", "mechanism": "ACSL4 is involved in ferroptosis; no significant change with GAMG, but required for lipid peroxidation.", "protein": "ACSL4", "protein_enriched": { "function": "Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids ", "gene_name": "ACSL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95573" }, "relationship_type": "causal", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may regulate SLC7A11 cell surface expression.", "mechanism": "SLC7A11 upregulation is linked to resistance to ferroptosis and tumor progression.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "causal", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation critical for collagen secretion.", "mechanism": "Collagen I accumulation is a hallmark of cirrhosis progression.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847116" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may affect SLC7A11 function.", "mechanism": "Targeting SLC7A11 to induce ferroptosis may prevent progression from fibrosis to cirrhosis.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847116" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may modulate IRF1 activity.", "mechanism": "IRF1-mediated repression of SLC7A11 may sensitize cells to ferroptosis, limiting tumorigenesis.", "protein": "IRF1", "protein_enriched": { "function": "Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060,", "gene_name": "IRF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10914" }, "relationship_type": "protective", "source_pmcid": "PMC11847116" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "ALG3 is involved in N-glycosylation, affecting glycoprotein maturation and cell signaling.", "mechanism": "Promotes tumor cell proliferation, migration, and invasion; high expression linked to poor prognosis.", "protein": "ALG3", "relationship_type": "oncogenic driver/therapeutic target", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "SFTPB is a secreted glycoprotein; glycosylation may affect its stability and function in lung tissue.", "mechanism": "Higher SFTPB expression correlates with better survival outcomes.", "protein": "SFTPB", "relationship_type": "protective biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may modulate KRT8's structural and signaling roles.", "mechanism": "High KRT8 expression associated with poor prognosis and increased tumor cell proliferation.", "protein": "KRT8", "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may influence S100A16's interaction with other proteins.", "mechanism": "High S100A16 expression linked to poor survival.", "protein": "S100A16", "protein_enriched": { "function": "Calcium-binding protein. Binds one calcium ion per monomer (PubMed:17030513). Can promote differentiation of adipocytes (in vitro) (By similarity). Overexpression in preadipocytes increases their prol", "gene_name": "S100A16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96FQ6" }, "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may affect chaperone activity and immune modulation.", "mechanism": "High HSPD1 expression associated with poor prognosis.", "protein": "HSPD1", "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may regulate redox activity and cell signaling.", "mechanism": "High TXN expression linked to poor survival.", "protein": "TXN", "protein_enriched": { "function": "Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:17182577, PubMed:1903223", "gene_name": "TXN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10599" }, "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may affect enzyme activity and stability.", "mechanism": "High LDHA expression associated with poor prognosis and metabolic reprogramming.", "protein": "LDHA", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHA", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G43223CG", "G57776ZS", "G84225JN", "G92406TI" ], "uniprot_id": "P00338" }, "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may modulate chromatin interactions.", "mechanism": "High HMGA1 expression linked to poor survival.", "protein": "HMGA1", "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may affect metabolic function.", "mechanism": "High ALDOA expression associated with poor prognosis.", "protein": "ALDOA", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also ", "gene_name": "ALDOA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04075" }, "relationship_type": "risk biomarker", "source_pmcid": "PMC11847145" }, { "confidence": "high", "disease": "Pan-cancer", "glycan_involvement": "ALG3 catalyzes N-glycan branching, impacting cell surface glycoprotein composition and tumor microenvironment.", "mechanism": "ALG3 overexpression observed in multiple tumor types; associated with genetic instability and immune evasion.", "protein": "ALG3", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC11847145" }, { "confidence": "medium", "disease": "Type B Aortic Intramural Hematoma (IMH)", "glycan_involvement": "LDL glycosylation affects its clearance and atherogenicity.", "mechanism": "Elevated LDL is associated with atherosclerosis, which predisposes to IMH progression.", "protein": "Low Density Lipoprotein (LDL)", "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "medium", "disease": "Type B Aortic Intramural Hematoma (IMH)", "glycan_involvement": "Cell surface glycoproteins mediate leukocyte adhesion and migration.", "mechanism": "Elevated WBC count indicates inflammation, correlating with IMH progression risk.", "protein": "White Blood Cell (WBC) glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "low", "disease": "Type B Aortic Intramural Hematoma (IMH)", "glycan_involvement": "Glycosylation may affect Hb stability and clearance.", "mechanism": "Hb levels reflect bleeding severity and oxygen delivery in IMH.", "protein": "Hemoglobin (Hb)", "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "low", "disease": "Liver Ischemia", "glycan_involvement": "AST is glycosylated, affecting its serum half-life.", "mechanism": "Elevated AST indicates liver ischemia secondary to IMH complications.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "low", "disease": "Liver Ischemia", "glycan_involvement": "ALT glycosylation modulates enzyme activity.", "mechanism": "ALT elevation signals hepatic injury in IMH patients.", "protein": "Alanine Transaminase (ALT)", "protein_enriched": { "function": "Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule", "gene_name": "rub", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24297" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation of ApoB affects LDL particle stability.", "mechanism": "ApoB is essential for LDL formation and atherogenesis, contributing to IMH risk.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "causal", "source_pmcid": "PMC11847199" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ApoE receptor binding.", "mechanism": "ApoE facilitates lipid clearance, reducing atherosclerosis and IMH risk.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective", "source_pmcid": "PMC11847199" }, { "confidence": "medium", "disease": "Type B Aortic Intramural Hematoma (IMH)", "glycan_involvement": "Glycosylation regulates matrix protein interactions and stability.", "mechanism": "Altered glycoprotein composition affects wall integrity, predisposing to IMH.", "protein": "Aortic wall extracellular matrix glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11847199" }, { "confidence": "medium", "disease": "Type B Aortic Intramural Hematoma (IMH)", "glycan_involvement": "Glycosylation controls endothelial barrier function.", "mechanism": "Endothelial glycoprotein dysfunction leads to vasa vasorum rupture and IMH.", "protein": "Vasa vasorum endothelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11847199" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "CRP glycosylation affects its immunomodulatory activity.", "mechanism": "CRP elevation reflects systemic inflammation in IMH.", "protein": "Acute phase glycoproteins (e.g., C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC11847199" }, { "confidence": "high", "disease": "Acquired hemophilia A (AHA)", "glycan_involvement": "Glycosylation of FVIII may affect immunogenicity and antibody binding.", "mechanism": "Autoantibodies (often IgG4) target and inhibit FVIII, leading to defective coagulation and bleeding.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "Not directly discussed; FVIII glycosylation may modulate immune recognition.", "mechanism": "Immune dysregulation in AIH may predispose to autoantibody formation against FVIII.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal/trigger", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Not directly discussed.", "mechanism": "Autoimmune processes in PBC may contribute to AHA via immune dysregulation and autoantibody production.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal/trigger", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Sj\u00f6gren's syndrome (SS)", "glycan_involvement": "Not directly discussed.", "mechanism": "SS is associated with increased risk of AHA due to immune dysregulation and autoantibody formation.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal/trigger", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Chronic hepatitis", "glycan_involvement": "vWF is heavily glycosylated; glycan changes may affect function and clearance.", "mechanism": "vWF levels are elevated in chronic liver disease, reflecting endothelial activation and altered hemostasis.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may affect FVIII stability and plasma levels.", "mechanism": "FVIII levels are typically elevated in cirrhosis, contrasting with decreased levels in AHA.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847240" }, { "confidence": "high", "disease": "Acquired hemophilia A (AHA)", "glycan_involvement": "Recombinant FVIII glycosylation affects pharmacokinetics and immunogenicity.", "mechanism": "Recombinant FVIII and bypassing agents are used to restore hemostasis in AHA.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847240" }, { "confidence": "high", "disease": "Acquired hemophilia A (AHA)", "glycan_involvement": "Glycosylation may affect assay sensitivity and antibody binding.", "mechanism": "Low FVIII activity and high FVIII inhibitor titers are diagnostic for AHA.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Acquired hemophilia A (AHA)", "glycan_involvement": "Glycosylation of FVIII may modulate these interactions.", "mechanism": "Autoantibodies may block FVIII interaction with vWF or phospholipids, disrupting tenase complex formation.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal", "source_pmcid": "PMC11847240" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation may affect vWF function and clearance.", "mechanism": "Elevated vWF is a marker of endothelial dysfunction in cirrhosis.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC11847240" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N- and O-glycosylation in extracellular domain modulates receptor function and ligand binding.", "mechanism": "Promotes macrophage infiltration and plaque formation via collagen binding and MMP regulation.", "protein": "DDR1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation sites in extracellular domain affect collagen interaction and signaling.", "mechanism": "Activates macrophage polarization and NLRP3 inflammasome via NF-\u03baB, promoting fibrosis.", "protein": "DDR1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Glomerulonephritis", "glycan_involvement": "N- and O-glycosylation modulates receptor stability and function.", "mechanism": "Regulates macrophage recruitment, cytokine secretion, and fibrosis in renal injury.", "protein": "DDR1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Alport Syndrome", "glycan_involvement": "Glycosylation influences receptor-ligand interactions in podocytes.", "mechanism": "Promotes renal fibrosis and lipotoxic injury via interaction with CD36 and collagen I.", "protein": "DDR1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "Glycosylation affects extracellular domain-mediated immune cell exclusion.", "mechanism": "Upregulated DDR1 correlates with poor prognosis, reduced immune infiltration, and promotes invasion via NF-\u03baB pathway.", "protein": "DDR1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation impacts receptor clustering and signaling.", "mechanism": "Promotes tumor aggressiveness, chemoresistance, and immune evasion by modulating TAM polarization.", "protein": "DDR1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation modulates receptor function in epithelial ovarian cancer cells.", "mechanism": "Upregulation drives tumor progression and immune evasion via M2 TAM polarization.", "protein": "DDR1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "N-glycosylation in extracellular domain affects ligand binding and signaling.", "mechanism": "Promotes EMT, invasion, and metastasis via AKT/GSK-3\u03b2/Slug pathway.", "protein": "DDR2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "medium", "disease": "Obesity-induced Inflammation", "glycan_involvement": "Glycosylation may regulate receptor stability and immune signaling.", "mechanism": "DDR2 in myeloid cells suppresses systemic inflammation; knockout exacerbates insulin resistance.", "protein": "DDR2", "relationship_type": "protective/causal", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Lung Fibrosis", "glycan_involvement": "N- and O-glycosylation modulates receptor activation and downstream signaling.", "mechanism": "Regulates fibroblast activation and collagen deposition; inhibition reduces fibrosis.", "protein": "DDR2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11847422" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated ALP reflects cholestasis and bile duct injury in PBC.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "GGT is a glycoprotein; glycosylation modulates its secretion and activity.", "mechanism": "Elevated GGT indicates bile duct injury and cholestasis.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "ALB is N-glycosylated; glycosylation affects half-life and function.", "mechanism": "Decreased ALB reflects impaired liver synthetic function in PBC.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "TB is measured as a marker; its transport is linked to glycoprotein carriers.", "mechanism": "Elevated TB indicates impaired bile excretion and advanced disease.", "protein": "Total bilirubin (TB)", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Platelet surface glycoproteins mediate immune interactions.", "mechanism": "PLR (platelet/lymphocyte ratio) is associated with inflammation and treatment response.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Neutrophil glycoproteins modulate adhesion and migration.", "mechanism": "NLR (neutrophil/lymphocyte ratio) is elevated in poor responders and advanced disease.", "protein": "Neutrophil", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Lymphocyte glycoproteins are critical for immune recognition.", "mechanism": "LMR (lymphocyte/monocyte ratio) is lower in PBC and predicts poor UDCA response.", "protein": "Lymphocyte", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Monocyte glycoproteins mediate inflammation.", "mechanism": "Monocyte levels (in LMR) reflect immune activation and prognosis.", "protein": "Monocyte", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation affects ALP serum stability.", "mechanism": "Elevated ALP is associated with cholestatic cirrhosis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "medium", "disease": "Acute-on-chronic liver failure", "glycan_involvement": "Altered glycosylation may affect ALB clearance.", "mechanism": "Low ALB predicts poor prognosis in liver failure.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC11847445" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glucuronidation increases solubility and bioactivity", "mechanism": "Inhibits uptake of oxidized LDL by macrophages and intracellular triglyceride accumulation", "protein": "Apigenin-7-O-\u03b2-D-glucuronide (A7GD)", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Growth retardation", "glycan_involvement": "Glycosylation enhances absorption and activity", "mechanism": "Promotes muscle growth via mTOR and Prmt7/PGC-1\u03b1/GPR56 pathways", "protein": "Apigenin-7-O-\u03b2-D-glucuronide (A7GD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glucuronidation increases antioxidant capacity", "mechanism": "Potent antioxidant activity, inhibits NO and pro-inflammatory cytokines", "protein": "Luteolin-7-O-\u03b2-D-glucuronide (L7GD)", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for bioactivity", "mechanism": "Suppresses NF-\u03baB, MAPK/AP-1, JAK/STAT pathways", "protein": "Luteolin-7-O-\u03b2-D-glucuronide (L7GD)", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Bacterial mastitis", "glycan_involvement": "Glucuronidation is main active plasma/tissue form", "mechanism": "Alleviates inflammation and oxidative stress in mammary glands", "protein": "Quercetin-3-O-\u03b2-D-glucuronide (Q3GD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Growth retardation", "glycan_involvement": "Glycosylation (rutinoside) increases stability and absorption", "mechanism": "Improves energy metabolism, milk yield, and meat quality", "protein": "Rutin (Quercetin 3-O-rutinoside)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847532" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation essential for activity", "mechanism": "Mitigates acetaminophen-induced hepatotoxicity via farnesol X receptor activation", "protein": "Schaftoside", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Diarrhea (pathogenic)", "glycan_involvement": "Glycosylation (caffeoylquinic acid) required for function", "mechanism": "Antibacterial, antifungal, antiviral; treats pathogenic diarrhea", "protein": "Chlorogenic acid (CGA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation increases bioactivity", "mechanism": "Reduces liver steatosis and protects against chemical-induced injury", "protein": "Chlorogenic acid (CGA)", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "medium", "disease": "Overexertion-induced injury", "glycan_involvement": "Di-caffeoylquinic acid glycosylation required", "mechanism": "Improves hypoxia tolerance and physical endurance", "protein": "Isochlorogenic acid A", "relationship_type": "protective", "source_pmcid": "PMC11847532" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "HSP90 is glycosylated, which may affect its stability and client protein interactions.", "mechanism": "HSP90 overexpression promotes thermoresistance and anti-apoptotic signaling in NSCLC; inhibition sensitizes tumor cells to mild photothermal therapy and chemotherapy.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847553" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "EGFR N-glycosylation modulates ligand binding and receptor activation.", "mechanism": "EGFR is involved in membrane microdomain signaling and is a hub gene in NSCLC targeted by curcumin.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847553" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Caspase 3 glycosylation may regulate its activation and stability.", "mechanism": "Caspase 3 downregulation is associated with reduced apoptosis in NSCLC; curcumin and HSP90 inhibition restore caspase 3 activity.", "protein": "CASP3", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "PI3K glycosylation can affect its localization and signaling.", "mechanism": "PI3K/AKT pathway is activated downstream of HSP90, promoting cell survival; inhibition leads to apoptosis.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847553" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "AKT glycosylation may influence its activity and interaction with HSP90.", "mechanism": "AKT is a client protein of HSP90; its phosphorylation is reduced upon HSP90 inhibition, suppressing anti-apoptotic signals.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847553" }, { "confidence": "low", "disease": "NSCLC", "glycan_involvement": "TNF glycosylation affects secretion and receptor binding.", "mechanism": "TNF is involved in membrane microdomain signaling and apoptosis regulation in NSCLC.", "protein": "TNF", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "low", "disease": "NSCLC", "glycan_involvement": "IL6 glycosylation modulates its stability and receptor interaction.", "mechanism": "IL6 is involved in apoptosis and inflammatory signaling in NSCLC; targeted by curcumin.", "protein": "IL6", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "low", "disease": "NSCLC", "glycan_involvement": "MPO glycosylation affects its enzymatic activity.", "mechanism": "MPO is enriched in vesicle lumen and may be involved in NSCLC microenvironment modulation.", "protein": "MPO", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "low", "disease": "NSCLC", "glycan_involvement": "ALB glycosylation influences its transport and stability.", "mechanism": "ALB is a vesicle lumen protein; altered levels may reflect NSCLC progression.", "protein": "ALB", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "low", "disease": "NSCLC", "glycan_involvement": "CASP8 glycosylation may regulate its activation.", "mechanism": "Caspase 8 is involved in apoptosis execution phase; targeted by curcumin in NSCLC.", "protein": "CASP8", "relationship_type": "biomarker", "source_pmcid": "PMC11847553" }, { "confidence": "high", "disease": "Diabetic periodontitis", "glycan_involvement": "RAGE binds advanced glycation end-products (AGEs), which are glycated proteins/lipids.", "mechanism": "AGE-RAGE signaling promotes inflammation and tissue damage in diabetic periodontitis.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "AGEs are non-enzymatic glycan modifications; RAGE is a glycoprotein receptor.", "mechanism": "AGE-RAGE pathway exacerbates diabetic complications via chronic inflammation.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Bone loss/osteoporosis", "glycan_involvement": "BSP is a glycoprotein; glycosylation affects bone matrix interactions.", "mechanism": "BSP upregulation promotes osteogenesis and bone regeneration.", "protein": "BSP", "relationship_type": "biomarker", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Bone loss/osteoporosis", "glycan_involvement": "OPG is a glycoprotein; glycosylation modulates receptor binding.", "mechanism": "OPG inhibits osteoclastogenesis, reducing bone resorption.", "protein": "OPG", "relationship_type": "protective", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "TNF-\u03b1 promotes inflammatory cytokine release and tissue destruction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "IL-6 is glycosylated; glycosylation influences stability and receptor interaction.", "mechanism": "IL-6 drives chronic inflammation and impairs insulin signaling.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "high", "disease": "Bacterial infection (P. gingivalis)", "glycan_involvement": "Not glycosylated; acts on bacterial glycan-rich surfaces (LPS).", "mechanism": "LL-37 disrupts bacterial membranes and biofilms, reducing infection.", "protein": "LL-37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847560" }, { "confidence": "high", "disease": "AGE-RAGE signaling complications", "glycan_involvement": "AGEs are glycan modifications; RAGE is a glycoprotein receptor.", "mechanism": "PL/LL-37 downregulates RAGE, reducing AGE-RAGE mediated tissue damage.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion.", "mechanism": "IL-1\u03b2 promotes inflammatory response and tissue destruction.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Not glycosylated; regulates transcription of glycoprotein cytokines.", "mechanism": "NF-\u03baB p65 activation increases inflammatory cytokine expression.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "causal", "source_pmcid": "PMC11847560" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Upregulated in serum; promotes proliferation, invasion, migration, angiogenesis, immune evasion, and metastasis.", "protein": "Suprabasin (SBSN)", "protein_enriched": { "function": "", "gene_name": "SBSN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "Q6UWP8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847613" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement reported.", "mechanism": "Downregulated in serum; loss promotes cell motility, invasion, and metastasis.", "protein": "Profilin-1 (PFN1)", "protein_enriched": { "function": "Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, i", "gene_name": "PFN1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G76295SF", "G49108TO" ], "uniprot_id": "P07737" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Early-stage breast cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation may regulate ECM interactions.", "mechanism": "Upregulated; enhances procollagen C-proteinase activity, facilitating ECM remodeling and tumor progression.", "protein": "Procollagen C-endopeptidase enhancer 1 (PCOLCE)", "protein_enriched": { "function": "Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity", "gene_name": "PCOLCE", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "Q15113" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Locally advanced breast cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect angiogenic activity.", "mechanism": "Upregulated; promotes angiogenesis and is linked to poor prognosis.", "protein": "Angiogenin (ANG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Metastatic breast cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation may influence immune modulation.", "mechanism": "Upregulated; may modulate immune cell infiltration and metastasis.", "protein": "WAP four-disulfide core domain protein 3 (WFDC3)", "protein_enriched": { "function": "Receptor with an affinity for galactose and fucose. Could be involved in endocytosis (By similarity)", "gene_name": "CLEC4F", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q8N1N0" }, "relationship_type": "biomarker", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Cytoskeletal glycoprotein; glycosylation may affect localization/function.", "mechanism": "Downregulated; acts as tumor suppressor by regulating focal adhesion and BRCA1 expression.", "protein": "Filamin-A (FLNA)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Membrane glycoprotein; glycosylation affects cell-cell adhesion.", "mechanism": "Downregulated; reduction increases invasion and motility.", "protein": "Desmoglein-2 (DSG2)", "protein_enriched": { "function": "A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filament", "gene_name": "DSG2", "glycan_count": 86, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G43669FQ", "G59324HL", "G00912UN", "G06356OH", "G08918WF", "G10486CT", "G20210JR", "G22310AV", "G27058EU", "G31916IQ", "G37412TK", "G41071NU", "G47518TP", "G59626AS", "G65184UU", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G86182NS", "G90659AW", "G04657PL", "G05049YU", "G07755XJ", "G10256JP", "G14972EH", "G23863VK", "G25418HZ", "G25451PN", "G34989PA", "G42124LM", "G43223CG", "G45395BF", "G60033FS", "G60177UT", "G62765YT", "G63381RX", "G64409MC", "G70441OD", "G70619PT", "G72667IM", "G75983OB", "G76295SF", "G80223IX", "G82830MN", "G83229XP", "G84452RH", "G85282JO", "G87661QW", "G90382BL", "G92135MA", "G95977AE", "G96577RX", "G47012YE", "G02528FI", "G07246CJ", "G10846ZT", "G11314AS", "G11870QZ", "G18647XP", "G20312EM", "G31544HA", "G34617SM", "G34730YF", "G44215PV", "G48414YA", "G60834IK", "G62894KT", "G63041LO", "G66760KM", "G70375MX", "G70894RY", "G75607BQ", "G77582RK", "G79666IR", "G81263BG", "G86795LJ", "G87123QX", "G91473PK", "G95133RI", "G82348BZ", "G57321FI", "G52527GH" ], "uniprot_id": "Q14126" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation critical for antibody function.", "mechanism": "Upregulated post-chemotherapy; may reflect immune response.", "protein": "Immunoglobulin heavy constant gamma 4", "relationship_type": "biomarker", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Metastatic breast cancer", "glycan_involvement": "Highly glycosylated; glycan changes may reflect disease state.", "mechanism": "Upregulated in metastatic cases; acute phase response protein.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. 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glycan profile changes in cancer.", "mechanism": "Upregulated in metastatic cases; modulates immune response.", "protein": "Alpha-1-acid glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC11847613" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding and clearance.", "mechanism": "Antipsychotics disrupt LDL-derived cholesterol exit from endosome/lysosome, leading to dyslipidemia.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11859610" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL is a glycoprotein; glycosylation modulates function and stability.", "mechanism": "HDL levels measured to assess metabolic dysfunction in clozapine-treated rats.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11859610" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Insulin glycosylation affects secretion and activity.", "mechanism": "Insulin levels measured to monitor metabolic syndrome in clozapine-treated rats.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC11859610" }, { "confidence": "medium", "disease": "Antipsychotic-induced metabolic dysfunction", "glycan_involvement": "Exosomal glycoproteins mediate cholesterol transport; glycosylation influences exosome formation and cargo.", "mechanism": "Curcumin accelerates release of cholesterol-containing exosomes, potentially mitigating metabolic dysfunction.", "protein": "Exosomal glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11859610" }, { "confidence": "medium", "disease": "Antipsychotic-induced metabolic dysfunction", "glycan_involvement": "LDL glycosylation affects receptor interaction and cellular uptake.", "mechanism": "Clozapine impairs LDL-derived cholesterol trafficking, contributing to metabolic dysfunction.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11859610" }, { "confidence": "low", "disease": "Weight gain", "glycan_involvement": "LDL glycosylation modulates metabolic clearance.", "mechanism": "Impaired LDL trafficking may contribute to weight gain in clozapine-treated rats.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC11859610" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of exosomal proteins affects lipid transport.", "mechanism": "Curcumin-induced exosome release may help normalize lipid profiles.", "protein": "Exosomal glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC11859610" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are used as a diagnostic marker for SLE and antiphospholipid syndrome.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation is essential for C3 stability and function.", "mechanism": "Low C3 levels indicate complement consumption due to immune complex deposition in SLE.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates C4 function and clearance.", "mechanism": "Low C4 levels reflect complement activation and are used in SLE diagnosis/activity monitoring.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "ANA target nuclear glycoprotein antigens; glycosylation may affect antigenicity.", "mechanism": "Presence of ANA is a diagnostic criterion for SLE.", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Target nuclear glycoproteins; glycosylation may influence immune recognition.", "mechanism": "Anti-dsDNA antibodies are highly specific for SLE and correlate with disease activity.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "medium", "disease": "Cardiac Tamponade", "glycan_involvement": "Glycosylation required for complement activation cascade.", "mechanism": "Low C3 due to SLE-associated complement activation contributes to pericardial inflammation and effusion.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC11869242" }, { "confidence": "medium", "disease": "Cardiac Tamponade", "glycan_involvement": "Glycosylation modulates C4 function.", "mechanism": "Decreased C4 in SLE leads to impaired immune complex clearance, promoting pericardial effusion.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "causal", "source_pmcid": "PMC11869242" }, { "confidence": "medium", "disease": "Autoimmune Polyglandular Syndrome Type II", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Anti-beta-2 glycoprotein I antibodies may be present in APS II, indicating autoimmunity.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "low", "disease": "Addison\u2019s Disease (Primary Adrenal Insufficiency)", "glycan_involvement": "Glycosylation essential for C3 function.", "mechanism": "Low C3 may reflect underlying autoimmune activity in Addison\u2019s disease.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "low", "disease": "Cardiac Tamponade", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Anti-beta-2 glycoprotein I antibodies may indicate risk for thrombotic or inflammatory cardiac complications.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC11869242" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "HS glycosylation modulates microglial activation and A\u03b2 plaque interaction.", "mechanism": "Microglial HS facilitates CD14/TLR4-dependent inflammatory response and co-deposits with A\u03b2 plaques, exacerbating amyloidopathy.", "protein": "Heparan sulfate (HS)", "relationship_type": "causal", "source_pmcid": "PMC11915540" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APOE structure and function in amyloid clearance.", "mechanism": "APOE4 increases risk and pathology; APOE4-Christchurch variant reduces amyloid deposition and neurotoxicity.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11915540" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation required for ApoA1 stability and anti-inflammatory function.", "mechanism": "ApoA1 administration delays disease progression, reduces neuroinflammation, and repairs microvasculature.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC11915540" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation critical for Reelin secretion and function.", "mechanism": "Reelin regulates neuronal migration and synaptic plasticity; deficiency impairs recovery post-stroke.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC11915540" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Potential glycosylation affects protein stability and interaction.", "mechanism": "YWHAB overexpression promotes malignancy; siRNA knockdown reduces proliferation and migration.", "protein": "14-3-3 beta (YWHAB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11915540" }, { "confidence": "medium", "disease": "Subarachnoid hemorrhage", "glycan_involvement": "Glycosylation essential for fibrinogen function in clot formation.", "mechanism": "Microthrombi formation detected by fibrinogen immunostaining; adropin reduces fibrinogen deposition and vascular damage.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11915540" }, { "confidence": "medium", "disease": "Subarachnoid hemorrhage", "glycan_involvement": "Glycosylation modulates ZO-1 localization and tight junction stability.", "mechanism": "Adropin preserves ZO-1 expression, maintaining blood-brain barrier integrity.", "protein": "ZO-1 (TJP1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC11915540" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of CD14 and HS interaction modulates inflammation.", "mechanism": "Microglial HS binds CD14, facilitating TLR4-dependent inflammatory response in AD.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC11915540" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may affect TH stability and activity.", "mechanism": "TH expression marks dopaminergic neuron differentiation; preserved in rAAV-transduced progenitors for PD therapy.", "protein": "Tyrosine hydroxylase (TH)", "relationship_type": "biomarker", "source_pmcid": "PMC11915540" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence APOE4-Ch protective effects.", "mechanism": "APOE4-Ch reduces amyloid plaques, neuronal dystrophy, and alters microglial response.", "protein": "Apolipoprotein E4-Christchurch (APOE4-Ch)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC11915540" }, { "confidence": "high", "disease": "Primary hyperparathyroidism", "glycan_involvement": "Glycosylation affects PTH stability and bioactivity.", "mechanism": "Elevated glycosylated PTH leads to hypercalcemia, causing neuropsychiatric symptoms including psychosis.", "protein": "Parathormone (PTH)", "relationship_type": "causal", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates prolactin receptor binding and serum half-life.", "mechanism": "Antipsychotic-induced hyperprolactinemia may worsen breast cancer prognosis.", "protein": "Prolactin", "protein_enriched": { "function": "Prolactin acts primarily on the mammary gland by promoting lactation", "gene_name": "PRL", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01236" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC11932181" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Enzyme glycosylation affects melanin and serotonin metabolism.", "mechanism": "Defective glycosylation in melanin synthesis may alter neurotransmitter metabolism, affecting schizophrenia risk.", "protein": "Melanin synthesis enzymes (e.g., 5-hydroxy-o-methyl transferase)", "relationship_type": "protective/causal", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Adrenal insufficiency (Addison's disease)", "glycan_involvement": "Glycosylation regulates ACTH secretion and immune recognition.", "mechanism": "Elevated glycosylated ACTH due to autoimmune destruction of adrenal cortex, leading to psychiatric symptoms.", "protein": "ACTH", "relationship_type": "biomarker/causal", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Neurobrucellosis", "glycan_involvement": "Surface glycoproteins facilitate immune evasion and CNS entry.", "mechanism": "Bacterial glycoproteins mediate CNS invasion, triggering neuropsychiatric symptoms.", "protein": "Brucella sp. surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC11932181" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "TSH glycosylation modulates receptor activation and hormone stability.", "mechanism": "Altered glycosylation of TSH affects thyroid hormone production, contributing to neuropsychiatric symptoms.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Adrenal insufficiency (Addison's disease)", "glycan_involvement": "Antibody glycosylation affects immune response and pathogenicity.", "mechanism": "Autoantibody (glycoprotein) targets adrenal enzyme, leading to hormone deficiency and psychiatric symptoms.", "protein": "21 Alpha hydroxylase antibody", "relationship_type": "causal", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Neurobrucellosis", "glycan_involvement": "IgM glycosylation modulates complement activation and pathogen clearance.", "mechanism": "IgM response to Brucella glycoproteins indicates active infection with neuropsychiatric involvement.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC11932181" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Aberrant N-glycosylation alters EGFR signaling and drug sensitivity.", "mechanism": "EGFR glycosylation status influences breast cancer progression and therapy response.", "protein": "Epidermal growth factor receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC11932181" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects CEA immunogenicity and detection.", "mechanism": "CEA glycoprotein levels correlate with breast cancer burden and prognosis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC11932181" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects ApoB stability and LDL particle clearance.", "mechanism": "Elevated ApoB/A1 ratio is associated with increased risk of atherosclerosis and cardiac events.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates ApoA1 function and HDL formation.", "mechanism": "Low ApoA1 levels correlate with increased cardiovascular risk.", "protein": "Apolipoprotein A1", "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Ischemic Heart Disease", "glycan_involvement": "LDL glycoprotein components influence receptor binding and clearance.", "mechanism": "High LDL levels promote plaque formation and ischemic events.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC11994198" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation may affect troponin stability and detection.", "mechanism": "Elevated troponin indicates myocardial injury.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Anaemia", "glycan_involvement": "Glycosylation can affect hemoglobin structure and function.", "mechanism": "Low hemoglobin levels diagnose anaemia.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "medium", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation influences ApoB secretion and lipid metabolism.", "mechanism": "Elevated ApoB is associated with metabolic syndrome and NAFLD risk.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects HDL particle formation and function.", "mechanism": "High HDL/ApoA1 levels are protective against atherosclerosis.", "protein": "HDL Cholesterol (ApoA1 carrier)", "relationship_type": "protective", "source_pmcid": "PMC11994198" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation of LDL affects its atherogenicity.", "mechanism": "Diabetes is associated with dyslipidemia, including elevated LDL.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates vascular effects of ApoB-containing particles.", "mechanism": "Elevated ApoB correlates with hypertension risk.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin reflects glucose levels.", "mechanism": "Glycated hemoglobin (HbA1c) is used to monitor diabetes control.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC11994198" }, { "confidence": "high", "disease": "Cardiovascular diseases", "glycan_involvement": "Cytochrome P450s are often glycosylated, but specific glycan involvement not detailed.", "mechanism": "Catalyzes final step in tanshinone biosynthesis, which are used to treat cardiovascular diseases.", "protein": "SmCYP71D375", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12017799" }, { "confidence": "high", "disease": "Cardiovascular diseases", "glycan_involvement": "No direct glycosylation described for SmMYB53.", "mechanism": "Upregulates SmCYP71D375, increasing tanshinone accumulation with cardiovascular protective effects.", "protein": "SmMYB53", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Potential glycosylation as P450, but not specified.", "mechanism": "Promotes biosynthesis of tanshinones with antitumor activity.", "protein": "SmCYP71D375", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Potential glycosylation as P450, but not specified.", "mechanism": "Enables production of anti-inflammatory tanshinones.", "protein": "SmCYP71D375", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Drought stress", "glycan_involvement": "No glycan involvement described.", "mechanism": "Participates in ABA signaling and drought stress response in plants.", "protein": "SmbZIP51", "relationship_type": "protective", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Biotic/abiotic stress", "glycan_involvement": "No glycan involvement described.", "mechanism": "Regulates stress responses by interacting with SmMYB53.", "protein": "SmbZIP51", "relationship_type": "protective", "source_pmcid": "PMC12017799" }, { "confidence": "high", "disease": "Phenolic acid deficiency", "glycan_involvement": "No glycan involvement described.", "mechanism": "Overexpression decreases phenolic acid biosynthesis by downregulating Sm4CL1, SmTAT1, SmCYP98A14.", "protein": "SmMYB53", "relationship_type": "causal", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Flavonoid deficiency", "glycan_involvement": "No glycan involvement described.", "mechanism": "Homologous to SlMYB1, which promotes flavonoid accumulation.", "protein": "SmMYB53", "relationship_type": "protective", "source_pmcid": "PMC12017799" }, { "confidence": "low", "disease": "Nitrogen signaling disorders", "glycan_involvement": "No glycan involvement described.", "mechanism": "TFs NLP6-like and nitrate regulatory gene 2 protein-like may interact with SmMYB53 in nitrogen signaling and tanshinone biosynthesis.", "protein": "SmMYB53", "relationship_type": "potential causal", "source_pmcid": "PMC12017799" }, { "confidence": "medium", "disease": "Salt tolerance/osmotic stress", "glycan_involvement": "No glycan involvement described.", "mechanism": "S23 subgroup MYBs regulate salt tolerance and osmotic stress in plants.", "protein": "SmMYB53", "relationship_type": "protective", "source_pmcid": "PMC12017799" }, { "confidence": "high", "disease": "Renal Cell Carcinoma (RCC)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation is essential for its secretion and receptor binding.", "mechanism": "TKIs inhibit VEGF signaling to suppress tumor angiogenesis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12046976" }, { "confidence": "high", "disease": "TKI-induced Hypertension", "glycan_involvement": "Glycosylation of VEGF is required for its normal function; disruption affects vascular homeostasis.", "mechanism": "Inhibition of VEGF signaling in normal endothelial cells by TKIs leads to hypertension.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12046976" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates VEGF stability and receptor interaction.", "mechanism": "VEGF inhibition impairs endothelial function, increasing blood pressure.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12046976" }, { "confidence": "high", "disease": "Familial Partial Lipodystrophy Type 2 (FPLD2)", "glycan_involvement": "Glycosylation may affect LMNA stability and localization, but not directly discussed.", "mechanism": "Pathogenic LMNA variants disrupt nuclear envelope integrity, leading to adipose tissue dysfunction.", "protein": "LMNA (Lamin A/C)", "relationship_type": "causal", "source_pmcid": "PMC12047169" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy Type 2 (FPLD2)", "glycan_involvement": "Leptin glycosylation affects secretion and stability.", "mechanism": "Low leptin levels reflect reduced subcutaneous fat mass in FPLD2.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047169" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Insulin glycosylation is essential for bioactivity.", "mechanism": "Insulin resistance is common in FPLD2, predisposing to diabetes.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047169" }, { "confidence": "low", "disease": "Infertility", "glycan_involvement": "FSH glycosylation modulates receptor binding and half-life.", "mechanism": "Altered FSH levels may contribute to reproductive dysfunction in FPLD2.", "protein": "FSH (Follicle Stimulating Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC12047169" }, { "confidence": "low", "disease": "Infertility", "glycan_involvement": "LH glycosylation modulates receptor binding and half-life.", "mechanism": "Altered LH levels may contribute to reproductive dysfunction in FPLD2.", "protein": "LH (Luteinizing Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC12047169" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "Leptin glycosylation affects hepatic signaling.", "mechanism": "Low leptin may promote hepatic fat accumulation in lipodystrophy.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047169" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "Potential impact on LMNA function via glycosylation, not directly discussed.", "mechanism": "LMNA mutation leads to abnormal fat distribution and hepatic steatosis.", "protein": "LMNA (Lamin A/C)", "relationship_type": "causal", "source_pmcid": "PMC12047169" }, { "confidence": "high", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycation (non-enzymatic addition of glucose to hemoglobin).", "mechanism": "HbA1c reflects chronic hyperglycemia due to non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "high", "disease": "Mauriac syndrome", "glycan_involvement": "Glycation level correlates with disease severity.", "mechanism": "Elevated HbA1c is associated with poor glycemic control, a key feature of Mauriac syndrome.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Growth retardation", "glycan_involvement": "Glycosylation affects IGF stability and receptor binding.", "mechanism": "Poor glycemic control in T1DM reduces IGF bioavailability, contributing to growth retardation.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "causal", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Mauriac syndrome", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT reflects hepatic injury and glycogen accumulation in Mauriac syndrome.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Mauriac syndrome", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "Elevated AST is indicative of liver dysfunction in Mauriac syndrome.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Mauriac syndrome", "glycan_involvement": "Glycosylation is critical for ALP activity and secretion.", "mechanism": "Elevated ALP is associated with hepatic involvement in Mauriac syndrome.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Mauriac syndrome", "glycan_involvement": "Glycosylation modulates IGF function.", "mechanism": "Reduced IGF due to poor glycemic control contributes to growth retardation in Mauriac syndrome.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "causal", "source_pmcid": "PMC12047170" }, { "confidence": "low", "disease": "Growth retardation", "glycan_involvement": "Glycosylation affects hormone stability and receptor interaction.", "mechanism": "Altered GnRH secretion may contribute to delayed puberty and growth retardation in Mauriac syndrome.", "protein": "Gonadotropin-Releasing Hormone (GnRH)", "protein_enriched": { "function": "Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones", "gene_name": "GNRH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01148" }, "relationship_type": "causal", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Hepatic glycogenosis", "glycan_involvement": "Glycation reflects systemic glucose excess.", "mechanism": "High HbA1c is associated with hepatic glycogen accumulation due to poor glycemic control.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "medium", "disease": "Type 1 diabetes mellitus (T1DM)", "glycan_involvement": "Glycosylation affects IGF bioactivity.", "mechanism": "IGF levels are reduced in poorly controlled T1DM, contributing to growth abnormalities.", "protein": "Insulin-like Growth Factor (IGF)", "relationship_type": "biomarker", "source_pmcid": "PMC12047170" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "PIIINP is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "Elevated serum PIIINP reflects increased liver fibrosis in WD.", "protein": "Procollagen type III N-terminal propeptide (PIIINP)", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Type IV collagen is heavily glycosylated, influencing ECM structure.", "mechanism": "Serum type IV collagen is increased in WD, indicating advanced liver fibrosis.", "protein": "Type IV collagen", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "As a glycosaminoglycan, its synthesis and turnover reflect ECM remodeling.", "mechanism": "Elevated hyaluronic acid in serum marks liver fibrosis and portal hypertension in WD.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "Laminin glycosylation modulates cell-matrix interactions.", "mechanism": "Serum laminin correlates with liver fibrosis severity in WD.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Albumin glycosylation may affect its half-life and function.", "mechanism": "Low serum albumin reflects impaired liver synthetic function in WD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "ATP7B is glycosylated; glycosylation may affect its trafficking and function.", "mechanism": "Mutations in ATP7B cause copper accumulation and WD pathogenesis.", "protein": "ATPase copper-transporting \u03b2 protein (ATP7B)", "protein_enriched": { "function": "Required for synaptic transmission regulation (PubMed:33539324). It probably controls the recruitement of voltage-gated calcium channels to the presynaptic membrane, and modulates neurotransmitter rel", "gene_name": "TSPOAP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95153" }, "relationship_type": "causal", "source_pmcid": "PMC12047222" }, { "confidence": "medium", "disease": "Splenomegaly/hypersplenism", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function.", "mechanism": "Low platelet count (glycoproteins) is a marker of hypersplenism in WD.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "WBC glycoproteins modulate immune response and trafficking.", "mechanism": "Elevated WBC count (glycoproteins) reflects inflammation and disease severity in WD.", "protein": "White blood cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation affects collagen's ECM integration.", "mechanism": "Serum type IV collagen is a marker of cirrhosis severity.", "protein": "Type IV collagen", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation influences PIIINP secretion and stability.", "mechanism": "PIIINP levels rise with increasing liver fibrosis and cirrhosis.", "protein": "Procollagen type III N-terminal propeptide (PIIINP)", "relationship_type": "biomarker", "source_pmcid": "PMC12047222" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects fetuin-A stability and secretion.", "mechanism": "Serum fetuin-A levels are elevated in NAFLD and reduced by curcumin, correlating with improved metabolic status.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "HBsAg glycosylation is essential for viral infectivity and immune evasion.", "mechanism": "Curcumin reduces HBsAg levels by destabilizing cccDNA and inhibiting viral protein expression.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation modulates HBeAg secretion and immunogenicity.", "mechanism": "Curcumin decreases HBeAg levels by suppressing HBV replication and mRNA transcription.", "protein": "HBeAg (Hepatitis B e antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03168" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "NTCP glycosylation is required for proper membrane localization and HBV binding.", "mechanism": "Curcumin modulates NTCP receptor activity, preventing HBV attachment and entry into hepatocytes.", "protein": "NTCP", "relationship_type": "therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "VEGF glycosylation regulates its secretion and receptor interaction.", "mechanism": "Curcumin downregulates VEGF, inhibiting angiogenesis and sinusoidal capillarization in fibrosis.", "protein": "VEGF", "relationship_type": "therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation of ICAM-1 is critical for cell-cell interaction.", "mechanism": "Curcumin reduces ICAM-1 expression, decreasing hepatic inflammation and leukocyte adhesion.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates VCAM-1 function and stability.", "mechanism": "Curcumin lowers VCAM-1 levels, attenuating inflammatory cell recruitment in NAFLD.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects TGF-beta secretion and receptor binding.", "mechanism": "Curcumin downregulates TGF-beta, reducing ECM deposition and fibrogenesis.", "protein": "TGF-beta", "relationship_type": "therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation may influence actin polymerization and cell motility.", "mechanism": "Curcumin suppresses alpha-SMA expression, indicating inhibition of hepatic stellate cell activation.", "protein": "Alpha-smooth muscle actin", "relationship_type": "biomarker", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Collagen glycosylation is essential for fibril formation and ECM structure.", "mechanism": "Curcumin reduces COL-I expression, limiting ECM accumulation and fibrosis.", "protein": "COL-I (Collagen type I)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12047230" }, { "confidence": "high", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation modulates VEGFA secretion and activity.", "mechanism": "Promotes pathological neovascularization in retina; ZYMT inhibits VEGFA expression.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation required for ICAM1 cell surface expression.", "mechanism": "ICAM1 mediates leukocyte adhesion and inflammation in retinal vessels.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12047248" }, { "confidence": "high", "disease": "Retinal Neovascularization", "glycan_involvement": "N-glycosylation affects CD31 function in cell adhesion.", "mechanism": "CD31 marks endothelial cells; elevated in neovascularization, reduced by ZYMT.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12047248" }, { "confidence": "high", "disease": "Retinal Cell Apoptosis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "BCL2 is anti-apoptotic; ZYMT increases BCL2 to reduce apoptosis.", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Retinal Cell Apoptosis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "CASP3 mediates apoptosis; ZYMT reduces CASP3 activity.", "protein": "CASP3", "relationship_type": "causal", "source_pmcid": "PMC12047248" }, { "confidence": "high", "disease": "Retinal Neovascularization", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "HIF1A upregulates VEGFA under hypoxia; ZYMT inhibits HIF1A.", "protein": "HIF1A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "STAT3 promotes inflammation and angiogenesis in DR.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "AKT1 activation drives vascular remodeling and neovascularization.", "protein": "AKT1", "relationship_type": "causal", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation affects TNF secretion.", "mechanism": "TNF promotes inflammation and vascular damage in DR.", "protein": "TNF", "relationship_type": "causal", "source_pmcid": "PMC12047248" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "N-glycosylation required for IL6 secretion.", "mechanism": "IL6 drives inflammatory response and VEGFA upregulation.", "protein": "IL6", "relationship_type": "causal", "source_pmcid": "PMC12047248" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Troponin T is a glycoprotein; glycosylation may affect stability and clearance.", "mechanism": "Elevated hs-cTnT indicates subclinical myocardial injury and predicts increased risk of CVD events and mortality.", "protein": "Cardiac Troponin T (hs-cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Troponin I is a glycoprotein; glycosylation may influence assay sensitivity.", "mechanism": "Elevated hs-cTnI is associated with myocardial injury and increased cardiovascular mortality.", "protein": "Cardiac Troponin I (hs-cTnI)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation may affect troponin release and detection in NAFLD context.", "mechanism": "Elevated hs-cTnT in NAFLD patients predicts higher all-cause and cardiovascular mortality.", "protein": "Cardiac Troponin T (hs-cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation may impact troponin stability and serum levels.", "mechanism": "Elevated hs-cTnI in NAFLD patients is independently associated with increased mortality risk.", "protein": "Cardiac Troponin I (hs-cTnI)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "CRP is heavily glycosylated; glycan structures modulate its inflammatory activity.", "mechanism": "Elevated CRP reflects systemic inflammation, contributing to atherosclerosis and CVD risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation affects fetuin-A secretion and function.", "mechanism": "Hepatokine fetuin-A from fatty liver may promote insulin resistance and vascular calcification, increasing CVD risk.", "protein": "Fetuin-A", "relationship_type": "causal", "source_pmcid": "PMC12047645" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "FGF21 glycosylation influences its stability and receptor binding.", "mechanism": "FGF21 from fatty liver may modulate cardiac metabolism and function.", "protein": "Fibroblast Growth Factor 21 (FGF21)", "relationship_type": "causal", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation may affect troponin half-life and detection.", "mechanism": "Elevated hs-cTnT predicts increased risk of death from any cause in NAFLD patients.", "protein": "Cardiac Troponin T (hs-cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation may influence troponin clearance and assay performance.", "mechanism": "Elevated hs-cTnI is a strong predictor of all-cause mortality in NAFLD.", "protein": "Cardiac Troponin I (hs-cTnI)", "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "medium", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "CRP glycosylation modulates its inflammatory properties.", "mechanism": "Elevated CRP in NAFLD reflects systemic inflammation and increased cardiovascular risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12047645" }, { "confidence": "high", "disease": "Glucocorticoid insufficiency", "glycan_involvement": "Abcb1b is a glycoprotein; glycosylation is essential for its proper folding and membrane localization.", "mechanism": "Loss of HHEX impairs Abcb1b expression, reducing steroid export and leading to glucocorticoid insufficiency.", "protein": "Abcb1b (P-glycoprotein/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12047992" }, { "confidence": "medium", "disease": "Adrenal lipid depletion", "glycan_involvement": "Glycosylation of Abcb1b affects its stability and function in steroid export.", "mechanism": "Impaired Abcb1b function due to HHEX loss disrupts lipid droplet protection, leading to lipid depletion.", "protein": "Abcb1b (P-glycoprotein/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12047992" }, { "confidence": "medium", "disease": "Adrenocortical dysfunction", "glycan_involvement": "Glycosylation status may modulate Abcb1b activity as a biomarker.", "mechanism": "Reduced Abcb1b expression marks loss of innermost adrenocortical cell identity and dysfunction.", "protein": "Abcb1b (P-glycoprotein/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12047992" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "vWF is a heavily glycosylated plasma protein; glycosylation affects its stability and function.", "mechanism": "Elevated vWF levels indicate endothelial dysfunction in CKD and are associated with increased cardiovascular risk.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "ICAM-1 is N-glycosylated, which modulates its cell adhesion properties.", "mechanism": "sICAM-1 is elevated in CKD, reflecting endothelial activation and inflammation; predicts mortality.", "protein": "Soluble intercellular adhesion molecule-1 (sICAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "VCAM-1 is N-glycosylated, influencing its interaction with leukocytes.", "mechanism": "sVCAM-1 is increased in CKD and predicts cardiovascular and all-cause mortality.", "protein": "Soluble vascular cell adhesion molecule-1 (sVCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans on glycoproteins, modulating cell adhesion and inflammation.", "mechanism": "Galectin-3 is associated with endothelial dysfunction and negatively impacts vascular reactivity in CKD.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "EMPs carry glycoproteins from the parent cell membrane, reflecting endothelial glycosylation status.", "mechanism": "EMPs are released from damaged endothelium, contribute to coagulation and inflammation, and are linked to atherosclerosis in CKD.", "protein": "Endothelial microparticles (EMPs)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "E-selectin is N-glycosylated; glycosylation is essential for ligand binding and leukocyte recruitment.", "mechanism": "sE-selectin is elevated in CKD, indicating endothelial activation and dysfunction.", "protein": "E-selectin (sE-selectin)", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Contains N-glycosylation sites; glycosylation affects secretion and function.", "mechanism": "Elevated levels are associated with endothelial dysfunction in hemodialysis patients.", "protein": "Angiopoietin-like protein 3", "protein_enriched": { "function": "Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the traffic", "gene_name": "ANGPTL3", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G62765YT", "G63381RX", "G90659AW", "G49108TO", "G29068FM", "G53434XO", "G28681TP", "G75983OB", "G08918WF", "G40574BA", "G59626AS", "G65184UU", "G70619PT", "G72747WU", "G72790NZ" ], "uniprot_id": "Q9Y5C1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Adiponectin is O-glycosylated, which is important for its multimerization and activity.", "mechanism": "High adiponectin levels are negatively associated with endothelial function in CKD.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates ICAM-1 function in leukocyte-endothelial interactions.", "mechanism": "sICAM-1 promotes leukocyte adhesion and vascular inflammation, contributing to atherosclerosis.", "protein": "Soluble intercellular adhesion molecule-1 (sICAM-1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12048126" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation regulates vWF multimerization and platelet binding.", "mechanism": "Elevated vWF is a marker of endothelial dysfunction and predicts cardiovascular events.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12048126" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Calprotectin is a glycoprotein; glycosylation may affect stability and detection in assays.", "mechanism": "Reflects neutrophil infiltration and intestinal inflammation; fecal levels correlate with endoscopic activity.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "CRP is N-glycosylated, which affects its solubility and clearance.", "mechanism": "Acute-phase reactant produced by the liver in response to inflammation; serum levels rise during active disease.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may influence calprotectin's stability in feces.", "mechanism": "Fecal calprotectin reflects neutrophil-driven mucosal inflammation in UC.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "low", "disease": "Crohn's disease", "glycan_involvement": "Highly glycosylated; glycan structures may affect its biomarker properties.", "mechanism": "Reported as a useful biomarker for CD in other studies (not directly assessed in this article).", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may affect calprotectin's detectability and function.", "mechanism": "Accuracy as a biomarker is higher in patients with short disease duration (<10 years), possibly due to less fibrosis and more active neutrophilic inflammation.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "N-glycosylation impacts CRP's function and clearance.", "mechanism": "Serum CRP correlates less strongly with endoscopic activity than calprotectin, especially in long-term disease.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may modulate protein stability in chronic inflammation.", "mechanism": "Fecal calprotectin is less accurate in long-term disease, possibly due to increased fibrosis and reduced neutrophil infiltration.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation status may vary with patient factors.", "mechanism": "Calprotectin levels are influenced by age, sex, surgery history, and immunomodulator use, which may affect its reliability.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may affect immunoassay detection.", "mechanism": "Fecal calprotectin is superior to CRP for reflecting mucosal healing and endoscopic remission in short-term CD.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "low", "disease": "Crohn's disease", "glycan_involvement": "Extensive glycosylation affects its biomarker utility.", "mechanism": "Mentioned as a useful biomarker in literature, but not directly studied here.", "protein": "Leucine-rich alpha-2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "LRG1", "glycan_count": 92, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08918WF", "G10486CT", "G11629QQ", "G12793SR", "G22140GZ", "G22310AV", "G23863VK", "G25418HZ", "G26330YA", "G27058EU", "G28681TP", "G37868ZX", "G40574BA", "G42358LZ", "G42962KI", "G44215PV", "G45395BF", "G45495MK", "G47737VJ", "G48414YA", "G50045TK", "G52131KU", "G57317CE", "G57776ZU", "G57818FI", "G57888GL", "G59626AS", "G62461SM", "G70232NH", "G71146HJ", "G72747WU", "G75798PH", "G75983OB", "G81295CK", "G82830MN", "G83229XP", "G83460ZZ", "G84452RH", "G95865ZB", "G98611JV", "G08293MJ", "G34730YF", "G44211QA", "G67324HN", "G94917XT", "G01650EU", "G04854VP", "G15169WU", "G18183SM", "G23221TW", "G24954UD", "G27947YN", "G30769VJ", "G31544HA", "G31852PQ", "G40834TG", "G40926MX", "G45504EY", "G47518TP", "G55412XP", "G56518TU", "G56784JY", "G57776ZS", "G59536GA", "G66163OV", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72398FA", "G78790NZ", "G80920RR", "G81263BG", "G86880BF", "G89865VY", "G90093AU", "G90386IR", "G90659AW", "G94470IW", "G96577RX", "G57321FI", "G07799LX", "G20425TQ", "G36131WL", "G55216FT", "G72797UR", "G78644BR", "G85740DB" ], "uniprot_id": "P02750" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048189" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycation (non-enzymatic addition of glucose to hemoglobin N-terminus)", "mechanism": "HbA1c reflects average blood glucose over 2\u20133 months; used to monitor glycemic control.", "protein": "Hemoglobin subunit beta (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12048193" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects trafficking and function.", "mechanism": "SGLT2 inhibitors block renal glucose reabsorption, lowering blood glucose.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Ischemic heart disease (IHD)", "glycan_involvement": "Glycation status reflects disease risk.", "mechanism": "Lower HbA1c after SGLT2i therapy correlates with improved glycemic control in IHD patients.", "protein": "Hemoglobin subunit beta (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Hypertension (HTN)", "glycan_involvement": "Glycation status reflects disease risk.", "mechanism": "Reduced HbA1c after SGLT2i therapy indicates improved glycemic control in hypertensive patients.", "protein": "Hemoglobin subunit beta (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycation status reflects disease risk.", "mechanism": "Lower HbA1c after SGLT2i therapy correlates with improved glycemic control in CKD patients.", "protein": "Hemoglobin subunit beta (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Peripheral neuropathy (PN)", "glycan_involvement": "Glycation status reflects disease risk.", "mechanism": "Lower HbA1c after SGLT2i therapy correlates with improved glycemic control in PN patients.", "protein": "Hemoglobin subunit beta (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12048193" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation may affect SGLT2 stability and renal localization.", "mechanism": "SGLT2 inhibitors improve renal function (eGFR) and reduce creatinine in CKD patients.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Ischemic heart disease (IHD)", "glycan_involvement": "Glycosylation may modulate SGLT2 function in cardiovascular tissues.", "mechanism": "SGLT2 inhibitors provide cardiovascular protection in IHD patients.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Hypertension (HTN)", "glycan_involvement": "Glycosylation may affect SGLT2-mediated sodium handling.", "mechanism": "SGLT2 inhibitors lower blood pressure in hypertensive patients.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12048193" }, { "confidence": "medium", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Glycosylation not directly implicated in DKA risk.", "mechanism": "No increase in DKA observed with SGLT2i use during Ramadan in this cohort.", "protein": "Sodium\u2013glucose cotransporter 2 (SGLT2)", "relationship_type": "protective", "source_pmcid": "PMC12048193" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Reflects collagen type III synthesis and deposition during fibrogenesis.", "protein": "PRO-C3", "relationship_type": "biomarker", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "N-glycosylation modulates detection and clearance.", "mechanism": "Serum PRO-C3 levels correlate with fibrosis in MASLD-CKD patients.", "protein": "PRO-C3", "relationship_type": "biomarker", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosaminoglycan structure essential for function.", "mechanism": "Elevated in serum during active fibrogenesis.", "protein": "Hyaluronic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation critical for matrix assembly.", "mechanism": "Serum laminin increases with extracellular matrix remodeling.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Promotes hepatic stellate cell activation and fibrogenesis.", "protein": "PDGF-D", "relationship_type": "causal", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "N-glycosylation modulates activity.", "mechanism": "Stimulates mesangial and interstitial cell proliferation.", "protein": "PDGF-D", "relationship_type": "causal", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Enhances hepatic stellate cell activation and collagen production.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12048807" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects secretion and receptor interaction.", "mechanism": "Master regulator of fibrogenesis via SMAD signaling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation modulates receptor binding.", "mechanism": "Promotes angiogenesis and sinusoidal capillarization in fibrotic liver.", "protein": "VEGFs", "relationship_type": "causal", "source_pmcid": "PMC12048807" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "N-glycosylation affects serum half-life.", "mechanism": "Elevated as a marker of inflammation in CKD and MASLD.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048807" }, { "confidence": "high", "disease": "CNSL", "glycan_involvement": "Likely N-glycosylated; glycosylation may affect stability and secretion in CSF.", "mechanism": "Elevated in CSF of CNSL patients, correlates with tumor burden and poor response to MAIVC.", "protein": "LCP1", "relationship_type": "biomarker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "N-glycosylation involved in cell surface localization.", "mechanism": "Downregulated in non-responders; predictive of early response to MAIVC.", "protein": "SGCE", "relationship_type": "biomarker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "Highly glycosylated; glycosylation modulates extracellular matrix interactions.", "mechanism": "Downregulated in non-responders; associated with MAIVC response.", "protein": "AGRN", "relationship_type": "biomarker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "Predicted N-glycosylation; may affect secretion and stability.", "mechanism": "Downregulated in non-responders; associated with MAIVC response.", "protein": "OLFML3", "relationship_type": "biomarker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "Possible glycosylation; functional impact unclear.", "mechanism": "Downregulated in non-responders; associated with MAIVC response.", "protein": "HRSP12", "relationship_type": "biomarker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "N-glycosylation may affect protein-protein interactions.", "mechanism": "Elevated in CSF with high tumor burden; decreases with treatment.", "protein": "YWHAE", "relationship_type": "tumor burden marker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "Possible glycosylation; may affect actin binding.", "mechanism": "Elevated in CSF with high tumor burden; decreases with treatment.", "protein": "PFN1", "relationship_type": "tumor burden marker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "Extensive N-glycosylation; affects immune function and stability.", "mechanism": "Elevated in CSF with high tumor burden; decreases with treatment.", "protein": "IGHM", "relationship_type": "tumor burden marker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "N-glycosylation modulates immune signaling.", "mechanism": "Elevated in CSF with high tumor burden; decreases with treatment.", "protein": "CD5L", "relationship_type": "tumor burden marker", "source_pmcid": "PMC12048878" }, { "confidence": "medium", "disease": "CNSL", "glycan_involvement": "N-glycosylation may regulate secretion and immune interactions.", "mechanism": "Potential target for monitoring and intervention due to its role in actin dynamics and tumor progression.", "protein": "LCP1", "relationship_type": "therapeutic target", "source_pmcid": "PMC12048878" }, { "confidence": "high", "disease": "Polycythemia", "glycan_involvement": "Glycosylation affects Hb stability and function.", "mechanism": "Elevated Hb levels indicate increased RBC mass in polycythemia, exacerbated by smoking-induced hypoxia.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12048899" }, { "confidence": "high", "disease": "Polycythemia", "glycan_involvement": "N-glycosylation is essential for erythropoietin stability and activity.", "mechanism": "Smoking-induced hypoxia increases erythropoietin secretion, driving RBC production.", "protein": "Erythropoietin", "relationship_type": "causal", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Glycosylation modulates albumin half-life and anti-inflammatory properties.", "mechanism": "Lower albumin in smokers reflects chronic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "N-glycosylation regulates IL-6 secretion and receptor binding.", "mechanism": "Smoking increases IL-6, promoting systemic inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor interactions.", "mechanism": "Smoking elevates TNF-\u03b1, contributing to chronic inflammation.", "protein": "Tumor Necrosis Factor Alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Glycosylation modulates IL-8 activity.", "mechanism": "Smoking increases IL-8, driving neutrophil recruitment and inflammation.", "protein": "Interleukin-8 (IL-8)", "relationship_type": "causal", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Surface glycoproteins mediate granulocyte maturation and function.", "mechanism": "Elevated immature granulocytes in smokers indicate inflammation.", "protein": "Immature Granulocyte Markers", "relationship_type": "biomarker", "source_pmcid": "PMC12048899" }, { "confidence": "low", "disease": "Polycythemia", "glycan_involvement": "Glycosylation influences LDH stability.", "mechanism": "LDH levels reflect cell turnover; altered in smokers and polycythemia.", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Apolipoprotein glycosylation affects VLDL metabolism.", "mechanism": "Higher VLDL in smokers increases cardiovascular risk.", "protein": "Very Low Density Lipoprotein (VLDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12048899" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation regulates leukocyte adhesion and migration.", "mechanism": "Smoking-induced leukocytosis and activation contribute to atherosclerosis.", "protein": "White Blood Cell Surface Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12048899" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "CD169 is a sialic acid-binding lectin; its function depends on glycan recognition.", "mechanism": "CD169+ macrophages in lymph nodes activate cytotoxic T lymphocytes (CTLs) via antigen presentation and co-stimulation, boosting anticancer immunity.", "protein": "CD169 (Siglec-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "High-mannose N-glycans on Man-MSA enable targeting to macrophage mannose receptors.", "mechanism": "Targets LN macrophages, induces CD169+ phenotype, enhances CD8+ T cell activation, and suppresses tumor growth.", "protein": "Man-MSA-mIFN\u03b1 fusion protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CD169 binds sialylated glycans on antigens for presentation.", "mechanism": "Number of CD169+ macrophages in LNs correlates with CTL infiltration and patient prognosis.", "protein": "CD169 (Siglec-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Bladder carcinoma (MB49)", "glycan_involvement": "Mannosylation enables LN macrophage targeting via CD206.", "mechanism": "Induces CD169+ macrophages, activates CD8+ T cells, and suppresses tumor growth, especially in tumors resistant to PD-L1 blockade.", "protein": "Man-MSA-mIFN\u03b1 fusion protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Lewis lung carcinoma (LLC)", "glycan_involvement": "High-mannose N-glycans mediate targeting.", "mechanism": "Induces CD169+ macrophages and CD8+ T cell activation, suppressing tumor growth.", "protein": "Man-MSA-mIFN\u03b1 fusion protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Resistance to immune checkpoint inhibitors", "glycan_involvement": "Glycan-mediated targeting to LN macrophages is essential for effect.", "mechanism": "Combination with PD-L1 blockade overcomes resistance by increasing CD8+ T cell infiltration.", "protein": "Man-MSA-mIFN\u03b1 fusion protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "Recognizes high-mannose N-glycans on Man-MSA.", "mechanism": "Expressed on LN macrophages; mediates uptake of mannosylated therapeutics.", "protein": "CD206 (mannose receptor)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "medium", "disease": "Cancer (solid tumors)", "glycan_involvement": "Native IFN\u03b1 is glycosylated; fusion to mannosylated albumin enhances targeting.", "mechanism": "Induces CD169 expression on macrophages, enhancing antitumor immunity.", "protein": "Interferon alpha (IFN\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "Mannosylation critical for LN macrophage targeting.", "mechanism": "Boosts immune response by increasing CD8+ T cell priming and infiltration.", "protein": "Man-MSA-mIFN\u03b1 fusion protein", "relationship_type": "protective", "source_pmcid": "PMC12049019" }, { "confidence": "low", "disease": "Cancer (solid tumors)", "glycan_involvement": "Highly glycosylated; serves as a reference.", "mechanism": "Used as a positive control for glycoprotein detection in PAS staining.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker (control)", "source_pmcid": "PMC12049019" }, { "confidence": "high", "disease": "Osteoarthritis with type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation upregulation in OA with diabetes", "mechanism": "Upregulated glycosylated C8\u03b1 may augment membrane attack complex activity, exacerbating cartilage destruction.", "protein": "Complement C8 alpha chain", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "COMP is a glycoprotein; glycosylation may affect stability and ECM interactions.", "mechanism": "Detected exclusively in OA cartilage by MS imaging; marker of cartilage degeneration.", "protein": "Cartilage oligomeric matrix protein (COMP)", "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation modulates ECM binding.", "mechanism": "Detected exclusively in OA cartilage; associated with cartilage degradation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Biglycan is a proteoglycan with glycosylation critical for function.", "mechanism": "Localized in OA cartilage by MALDI-MSI; involved in ECM structure.", "protein": "Biglycan", "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Prolargin is a glycoprotein; glycosylation affects ECM interactions.", "mechanism": "Identified in OA cartilage; ECM component.", "protein": "Prolargin", "protein_enriched": { "function": "Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor", "gene_name": "BHMT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2M3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Decorin is a proteoglycan; glycosylation essential for ECM function.", "mechanism": "Detected in OA cartilage; regulates collagen fibrillogenesis.", "protein": "Decorin", "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Aggrecan is heavily glycosylated; glycosylation critical for water retention and ECM structure.", "mechanism": "Localized in OA cartilage; major cartilage proteoglycan.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "CRTAC1 is a glycoprotein; glycosylation may affect secretion and function.", "mechanism": "Exclusively upregulated in late-stage OA synovial fluid.", "protein": "CRTAC1", "protein_enriched": { "function": "Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-indu", "gene_name": "ASPN", "glycan_count": 124, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G01485JJ", "G01650EU", "G02030ZB", "G02315DX", "G02815KT", "G03382KH", "G04657PL", "G05049YU", "G05962QB", "G06356OH", "G07755XJ", "G08110WX", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G11629QQ", "G14972EH", "G14994KB", "G17208MA", "G20210JR", "G20528HD", "G22310AV", "G23505EP", "G23719VF", "G23863VK", "G24954UD", "G25418HZ", "G25451PN", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G31916IQ", "G34617SM", "G34989PA", "G35029YA", "G35253PZ", "G35541EV", "G36379GD", "G37509XX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G44215PV", "G45395BF", "G45504EY", "G46503DX", "G46524LG", "G46687AB", "G46691LC", "G47644PP", "G50045TK", "G50757KG", "G51640FO", "G57776ZS", "G58087IP", "G59626AS", "G60033FS", "G61256FT", "G63041LO", "G64394MX", "G64409MC", "G65019XG", "G65092SV", "G65184UU", "G66621EA", "G66760KM", "G68490OW", "G70418MS", "G70441OD", "G70619PT", "G70822IO", "G72667IM", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G74430RZ", "G76295SF", "G77547TA", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80333GO", "G80920RR", "G81198YO", "G81263BG", "G82592ZH", "G83460ZZ", "G83646BJ", "G84452RH", "G84862VB", "G85554PZ", "G86182NS", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88891KO", "G89045VA", "G89098OM", "G90093AU", "G90382BL", "G90659AW", "G90734RJ", "G91636VS", "G92406TI", "G92551JA", "G93718GY", "G94470IW", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "Q9BXN1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Collagen is glycosylated; glycosylation affects fibril formation.", "mechanism": "Increased in early OA synovial fluid, decreased in late OA.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Collagen is glycosylated; glycosylation affects ECM structure.", "mechanism": "Increased in early OA synovial fluid, decreased in late OA.", "protein": "COL3A1", "relationship_type": "biomarker", "source_pmcid": "PMC12049056" }, { "confidence": "high", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not directly addressed; possible glycosylation due to enzyme class.", "mechanism": "Regulates glycerophospholipid metabolism; altered expression affects cell growth, proliferation, and protein transport in decidua, contributing to URSA pathogenesis.", "protein": "Phospholipase D1", "protein_enriched": { "function": "Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transductio", "gene_name": "PLD1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q13393" }, "relationship_type": "causal", "source_pmcid": "PMC12049100" }, { "confidence": "high", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not directly addressed; possible glycosylation due to enzyme class.", "mechanism": "Key enzyme in phosphatidylcholine biosynthesis; downregulation impairs glycerophospholipid synthesis, reducing cell proliferation and increasing apoptosis in decidual cells.", "protein": "Cholinephosphotransferase 1", "protein_enriched": { "function": "Catalyzes the final step of de novo phosphatidylcholine (PC) synthesis, i.e. the transfer of choline phosphate from CDP-choline to the free hydroxyl of a diacylglycerol (DAG), producing a PC. It there", "gene_name": "CHPT1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WUD6" }, "relationship_type": "causal", "source_pmcid": "PMC12049100" }, { "confidence": "medium", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not directly addressed; possible glycosylation due to enzyme class.", "mechanism": "Involved in phospholipid hydrolysis; dysregulation affects lipid mediator balance and cell membrane integrity in decidua.", "protein": "Phospholipase A2 group IIA", "protein_enriched": { "function": "Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:1", "gene_name": "PLA2G2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P14555" }, "relationship_type": "causal", "source_pmcid": "PMC12049100" }, { "confidence": "high", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not applicable (lipid).", "mechanism": "Decreased levels in URSA; reflects disrupted glycerophospholipid metabolism.", "protein": "Phosphatidylethanolamine (PE)", "relationship_type": "biomarker", "source_pmcid": "PMC12049100" }, { "confidence": "high", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not applicable (lipid).", "mechanism": "Decreased levels in URSA; indicates impaired membrane lipid synthesis.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "biomarker", "source_pmcid": "PMC12049100" }, { "confidence": "medium", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not applicable (lipid).", "mechanism": "Decreased levels in URSA; associated with altered cell membrane composition.", "protein": "Phosphatidylserine (PS)", "relationship_type": "biomarker", "source_pmcid": "PMC12049100" }, { "confidence": "medium", "disease": "Unexplained recurrent spontaneous abortion (URSA)", "glycan_involvement": "Not applicable (lipid).", "mechanism": "Altered levels in URSA; impacts mitochondrial function and apoptosis regulation.", "protein": "Cardiolipin (CL)", "relationship_type": "biomarker", "source_pmcid": "PMC12049100" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Not directly addressed.", "mechanism": "Phospholipid metabolism enzymes are implicated in APS, which is associated with increased risk of RSA.", "protein": "Phospholipase D1", "protein_enriched": { "function": "Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transductio", "gene_name": "PLD1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q13393" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049100" }, { "confidence": "low", "disease": "Gestational diabetes", "glycan_involvement": "Not directly addressed.", "mechanism": "Abnormal expression linked to metabolic disorders affecting pregnancy outcomes.", "protein": "Phospholipase A2 group IIA", "protein_enriched": { "function": "Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:1", "gene_name": "PLA2G2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P14555" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049100" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Not directly addressed.", "mechanism": "Abnormal expression associated with carcinogenesis; mentioned as a parallel to its role in URSA.", "protein": "Phospholipase A2 group IIA", "protein_enriched": { "function": "Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:1", "gene_name": "PLA2G2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P14555" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049100" }, { "confidence": "high", "disease": "Multidrug-resistant tuberculosis", "glycan_involvement": "P-glycoprotein is a glycosylated membrane transporter; glycosylation is required for its proper folding and function.", "mechanism": "Bedaquiline is a substrate of P-glycoprotein, which affects its pharmacokinetics and efficacy in MDR-TB treatment.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049102" }, { "confidence": "medium", "disease": "Cardiotoxicity", "glycan_involvement": "Glycosylation affects P-glycoprotein trafficking and drug efflux capacity.", "mechanism": "Inhibition or saturation of P-glycoprotein by carvedilol increases bedaquiline plasma levels, raising risk of cardiotoxicity.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12049102" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation modulates P-glycoprotein stability and localization.", "mechanism": "Elevated bedaquiline exposure due to P-glycoprotein inhibition may increase hepatotoxicity risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12049102" }, { "confidence": "medium", "disease": "Phospholipidosis", "glycan_involvement": "Proper glycosylation is necessary for P-glycoprotein function in drug clearance.", "mechanism": "Increased bedaquiline levels from P-glycoprotein inhibition can promote phospholipidosis.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12049102" }, { "confidence": "high", "disease": "Cirrhotic portal hypertension (CPH)", "glycan_involvement": "Zona pellucida domain suggests glycosylation; glycan status may affect secretion/localization.", "mechanism": "Downregulated in CPH; may regulate LSEC function and lipid metabolism, affecting portal resistance.", "protein": "OIT3", "relationship_type": "biomarker", "source_pmcid": "PMC12049105" }, { "confidence": "high", "disease": "Cirrhotic portal hypertension (CPH)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect ECM interactions.", "mechanism": "Upregulated in CPH; promotes collagen cross-linking, ECM stiffness, and fibrosis, increasing intrahepatic resistance.", "protein": "LOXL1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Potential glycosylation affects function in hepatocytes.", "mechanism": "OIT3 downregulation may disrupt LSEC mechanosensing, exacerbating cirrhosis progression.", "protein": "OIT3", "relationship_type": "protective", "source_pmcid": "PMC12049105" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may regulate ECM cross-linking activity.", "mechanism": "LOXL1 upregulation drives ECM remodeling and fibrosis in cirrhosis.", "protein": "LOXL1", "relationship_type": "causal", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect cell-cell interactions in tumor microenvironment.", "mechanism": "OIT3 is a marker for alternatively activated macrophages and promotes metastasis.", "protein": "OIT3", "relationship_type": "biomarker", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Hypertrophic scars", "glycan_involvement": "Glycosylation may modulate ECM binding.", "mechanism": "LOXL1 promotes fibroblast proliferation and ECM accumulation via Smad signaling.", "protein": "LOXL1", "relationship_type": "causal", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "LOXL1 upregulation reduces synovial inflammation by blocking PI3K/AKT signaling.", "protein": "LOXL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Pelvic organ prolapse", "glycan_involvement": "Glycosylation may affect ECM assembly.", "mechanism": "LOXL1 deficiency impairs elastic fiber formation, leading to prolapse.", "protein": "LOXL1", "relationship_type": "causal", "source_pmcid": "PMC12049105" }, { "confidence": "high", "disease": "Cirrhotic portal hypertension (CPH)", "glycan_involvement": "Glycosylation may regulate ECM cross-linking efficiency.", "mechanism": "LOXL1-mediated ECM cross-linking increases portal pressure.", "protein": "LOXL1", "relationship_type": "causal", "source_pmcid": "PMC12049105" }, { "confidence": "medium", "disease": "Cirrhotic portal hypertension (CPH)", "glycan_involvement": "Glycosylation may affect stability and function.", "mechanism": "OIT3 may maintain LSEC homeostasis and prevent excessive portal resistance.", "protein": "OIT3", "relationship_type": "protective", "source_pmcid": "PMC12049105" }, { "confidence": "high", "disease": "Erosive Pustular Dermatosis of the Scalp (EPDS)", "glycan_involvement": "EGFR is a glycoprotein; glycosylation is essential for ligand binding and receptor function.", "mechanism": "EGFR inhibition by erlotinib disrupts keratinocyte function, triggers neutrophilic inflammation, and leads to follicular damage and EPDS.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12049118" }, { "confidence": "high", "disease": "Acneiform Rash", "glycan_involvement": "EGFR glycosylation modulates receptor activity and downstream signaling.", "mechanism": "EGFR inhibition alters keratinocyte proliferation and cytokine profiles, resulting in neutrophil-mediated acneiform eruptions.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12049118" }, { "confidence": "medium", "disease": "Alopecia", "glycan_involvement": "Glycosylation of EGFR affects its localization and function in hair follicles.", "mechanism": "EGFR inhibition impairs hair follicle cycling and integrity, leading to alopecia and scarring.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12049118" }, { "confidence": "medium", "disease": "Acute Generalized Expulsive Pustulosis (AGEP)", "glycan_involvement": "EGFR glycosylation status may influence susceptibility to drug-induced inflammation.", "mechanism": "EGFR inhibition by drugs (e.g., lapatinib) induces neutrophilic dermatosis and pustular eruptions.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "causal", "source_pmcid": "PMC12049118" }, { "confidence": "medium", "disease": "Erosive Pustular Dermatosis of the Scalp (EPDS)", "glycan_involvement": "Glycosylation regulates EGFR stability and cell surface expression.", "mechanism": "Elevated EGFR expression in hair follicles and keratinocytes correlates with severity of EPDS.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12049118" }, { "confidence": "medium", "disease": "Acneiform Rash", "glycan_involvement": "Glycosylation affects EGFR signaling and rash development.", "mechanism": "Acneiform rash is a pharmacodynamic biomarker of EGFR inhibitor efficacy.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12049118" }, { "confidence": "high", "disease": "Erosive Pustular Dermatosis of the Scalp (EPDS)", "glycan_involvement": "Glycosylation is required for EGFR drug binding and activity.", "mechanism": "EGFR is targeted by inhibitors (e.g., erlotinib) for cancer therapy, but off-target effects cause EPDS.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049118" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycine conjugation is a glyco-modification critical for function.", "mechanism": "GDCA levels are associated with insulin resistance and modulate insulin clearance and GLP-1 secretion.", "protein": "Glycodeoxycholic acid (GDCA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12049121" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Taurine conjugation is a glyco-modification relevant to activity.", "mechanism": "TDCA is linked to insulin resistance and glucose homeostasis modulation.", "protein": "Taurodeoxycholic acid (TDCA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12049121" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "No direct glycosylation, but downstream effects involve glycan-modified molecules.", "mechanism": "LCA promotes synthesis of CA-7S and stimulates GLP-1 secretion, improving glucose metabolism.", "protein": "Lithocholic acid (LCA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12049121" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Sulfation is a glyco-related modification.", "mechanism": "CA-7S is negatively correlated with visceral adiposity index and has antidiabetic effects.", "protein": "Bile acid-7-sulfate (CA-7S)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "No direct glycosylation, but conjugated forms are relevant.", "mechanism": "DCA administration reduces blood glucose in animal models.", "protein": "Deoxycholic acid (DCA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049121" }, { "confidence": "high", "disease": "Obesity (visceral/abdominal)", "glycan_involvement": "Glycine conjugation is a glyco-modification.", "mechanism": "GDCA levels are associated with visceral adiposity indices (VAI, CVAI).", "protein": "Glycodeoxycholic acid (GDCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "high", "disease": "Obesity (visceral/abdominal)", "glycan_involvement": "Taurine conjugation is a glyco-modification.", "mechanism": "TDCA levels correlate with visceral adiposity and metabolic phenotype.", "protein": "Taurodeoxycholic acid (TDCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "No direct glycosylation.", "mechanism": "AlloLCA correlates positively with triglycerides and visceral adiposity index.", "protein": "Allolithocholic acid (alloLCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "medium", "disease": "Obesity (visceral/abdominal)", "glycan_involvement": "Glycine conjugation and sulfation are glyco-modifications.", "mechanism": "GCDCA-3S is negatively correlated with CVAI, indicating lower visceral adiposity.", "protein": "Glycochenodeoxycholic acid-3-sulfate (GCDCA-3S)", "relationship_type": "biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Oxidation, not glycosylation.", "mechanism": "3-oxo-CA differentiates between non-diabetic and lean T2DM phenotypes.", "protein": "3-oxo-cholic acid (3-oxo-CA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049121" }, { "confidence": "high", "disease": "Rectal cancer", "glycan_involvement": "CEA is heavily N-glycosylated, which affects its stability and detection in serum.", "mechanism": "Elevated serum CEA is associated with presence and progression of rectal cancer.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049155" }, { "confidence": "medium", "disease": "Lymph node metastasis in rectal cancer", "glycan_involvement": "Glycosylation of CEA influences its secretion and immunogenicity.", "mechanism": "Elevated preoperative CEA correlates with increased risk of lymph node metastasis.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049155" }, { "confidence": "high", "disease": "Rectal cancer", "glycan_involvement": "CA19.9 is a sialylated glycan epitope (sLea) on glycoproteins/lipids, detected in serum.", "mechanism": "Elevated serum CA19.9 is associated with rectal cancer, especially in advanced stages.", "protein": "Carbohydrate antigen 19-9 (CA19.9)", "relationship_type": "biomarker", "source_pmcid": "PMC12049155" }, { "confidence": "high", "disease": "Lymph node metastasis in rectal cancer", "glycan_involvement": "Altered glycosylation (sLea expression) reflects tumor cell dissemination.", "mechanism": "Preoperative elevation of CA19.9 is an independent risk factor for lymph node metastasis.", "protein": "Carbohydrate antigen 19-9 (CA19.9)", "relationship_type": "biomarker", "source_pmcid": "PMC12049155" }, { "confidence": "high", "disease": "Bone fracture", "glycan_involvement": "Glycosylation of hydroxylysine modulates fibril alignment and cell adhesion.", "mechanism": "Collagen type I hydrogels mimic ECM, supporting bone tissue regeneration.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "high", "disease": "Cartilage damage", "glycan_involvement": "Glycosylation affects cell-matrix interactions and hydrogel properties.", "mechanism": "Collagen type I hydrogels provide a scaffold for cartilage repair and cell migration.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Cardiac tissue injury", "glycan_involvement": "Glycosylation may influence cell adhesion and hydrogel remodeling.", "mechanism": "Collagen type I hydrogels support cardiac tissue engineering and cell growth.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "high", "disease": "Burned skin", "glycan_involvement": "Glycosylation modulates cell adhesion and fibril organization in skin.", "mechanism": "Collagen type I hydrogels promote skin regeneration and wound closure.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "high", "disease": "Wound healing impairment", "glycan_involvement": "Glycosylation sites facilitate cell-matrix interactions.", "mechanism": "Collagen type I-based dressings accelerate wound healing by supporting cell migration.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Tissue regeneration failure", "glycan_involvement": "Glycosylation impacts hydrogel structure and biological performance.", "mechanism": "Collagen type I hydrogels provide a matrix for tissue regeneration in TERM.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Wound healing impairment", "glycan_involvement": "Changes in glycosylation affect cell adhesion and ECM remodeling.", "mechanism": "Altered glycosylation of collagen type I may indicate impaired wound healing.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Bone fracture", "glycan_involvement": "Glycosylation of hydroxylysine correlates with bone matrix quality.", "mechanism": "Collagen type I glycosylation status may reflect bone healing capacity.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Cartilage damage", "glycan_involvement": "Glycosylation modulates cell adhesion and cartilage matrix formation.", "mechanism": "Collagen type I glycosylation patterns may indicate cartilage repair status.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049273" }, { "confidence": "medium", "disease": "Tissue regeneration failure", "glycan_involvement": "Lack of glycosylation disrupts fibril alignment and cell-matrix interactions.", "mechanism": "Insufficient glycosylation of collagen type I may impair tissue regeneration.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "causal", "source_pmcid": "PMC12049273" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "FBG is a glycoprotein; glycosylation affects its stability and function in coagulation and inflammation.", "mechanism": "FBG levels correlate with RA disease activity and joint inflammation; FBG deposition contributes to pannus formation.", "protein": "Fibrinogen (FBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "DD is a glycopeptide fragment from glycosylated fibrinogen.", "mechanism": "Elevated DD reflects increased coagulation and fibrinolysis, correlating with RA severity.", "protein": "D-dimer (DD)", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Platelet surface glycoproteins mediate activation and aggregation; glycosylation modulates function.", "mechanism": "Increased platelet count and activation are associated with RA activity and inflammation.", "protein": "Platelet (PLT) glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "CRP is glycosylated, which affects its stability and immune recognition.", "mechanism": "CRP is an acute-phase reactant; high levels predict RA disease activity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Anxiety (SAS)", "glycan_involvement": "Glycosylation may modulate FBG's inflammatory properties.", "mechanism": "High FBG levels are associated with increased anxiety scores in RA patients.", "protein": "Fibrinogen (FBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Depression (SDS)", "glycan_involvement": "Glycosylation may modulate FBG's inflammatory properties.", "mechanism": "High FBG levels are associated with increased depression scores in RA patients.", "protein": "Fibrinogen (FBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Anxiety (SAS)", "glycan_involvement": "Platelet glycoprotein glycosylation affects activation and immune interactions.", "mechanism": "Elevated platelet count is predictive of anxiety in RA patients.", "protein": "Platelet (PLT) glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Anxiety (SAS)", "glycan_involvement": "CRP glycosylation modulates immune signaling.", "mechanism": "High CRP levels are associated with increased anxiety in RA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Depression (SDS)", "glycan_involvement": "CRP glycosylation modulates immune signaling.", "mechanism": "High CRP levels are associated with increased depression in RA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049676" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "Therapeutic modulation objective is the glycosylated FBG.", "mechanism": "Xinfeng Capsule (XFC) improves FBG levels, reducing RA disease activity and improving quality of life.", "protein": "Fibrinogen (FBG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049676" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Binds high-mannose and complex N-glycans (including paucimannose, fucosylated forms) on GBM cell surfaces.", "mechanism": "Induces apoptosis, autophagy, cell cycle arrest (G2/M), and inhibits migration in U-87 MG cells; crosses BBB when nano-encapsulated.", "protein": "Tarin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049682" }, { "confidence": "high", "disease": "Breast adenocarcinoma", "glycan_involvement": "Binds high-mannose and complex N-glycans (Lewis Y, antigen H2) on carcinoma cells.", "mechanism": "Induces apoptosis, autophagy, cell cycle arrest (G0/G1), and inhibits migration in MDA-MB-231 cells.", "protein": "Tarin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049682" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N-glycosylation; upregulation linked to antitumoral response.", "mechanism": "High levels in aggressive GBM cells; involved in negative control of proliferation, migration, invasion.", "protein": "Paucimannose glycoepitope", "relationship_type": "biomarker", "source_pmcid": "PMC12049682" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Fucosylation of paucimannose N-glycans.", "mechanism": "Associated with tumor progression.", "protein": "Fucosylated paucimannose", "relationship_type": "causal", "source_pmcid": "PMC12049682" }, { "confidence": "medium", "disease": "Tumor progression/metastasis", "glycan_involvement": "High N-glycosylation; lectin binding (e.g., Galanthus nivalis agglutinin, tarin family).", "mechanism": "Soluble CD73 promotes tumor progression and immunosuppression.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12049682" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N- and O-glycosylation modulate receptor signaling.", "mechanism": "Aberrant glycosylation contributes to GBM pathogenesis and resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12049682" }, { "confidence": "medium", "disease": "Tumor progression/metastasis", "glycan_involvement": "N-glycosylation; lectin binding may modulate function.", "mechanism": "Glycosylation affects activity; involved in invasion/migration.", "protein": "Matrix Metalloproteinases", "relationship_type": "causal", "source_pmcid": "PMC12049682" }, { "confidence": "medium", "disease": "Tumor progression/metastasis", "glycan_involvement": "N-glycosylation; potential lectin interaction.", "mechanism": "Glycosylation regulates cell adhesion and migration.", "protein": "CD98hc", "relationship_type": "causal", "source_pmcid": "PMC12049682" }, { "confidence": "low", "disease": "Chemoresistance", "glycan_involvement": "Glycosylation may affect stability/activity.", "mechanism": "Tarin reduces COX2 expression, decreasing PGE2-mediated inflammation.", "protein": "COX2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049682" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Not directly glycosylated, but activation downstream of glycan-lectin interactions.", "mechanism": "Activated by tarin-induced apoptosis.", "protein": "Caspase 3/7", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049682" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Elevated anti-beta-2 glycoprotein I antibodies are associated with SLE and antiphospholipid syndrome.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for C3 function and stability.", "mechanism": "Low C3 levels indicate complement consumption due to immune complex formation in SLE.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates C4 activity.", "mechanism": "Low C4 levels reflect complement activation and immune complex deposition in SLE.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "Anti-SSA/Ro antibodies are frequently detected in SLE and related autoimmune diseases.", "protein": "Sjogren's syndrome antigen A (SSA/Ro)", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Anti-SSB/La antibodies are associated with SLE and Sjogren's syndrome.", "protein": "Sjogren's syndrome antigen B (SSB/La)", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Anti-RNP antibodies are diagnostic markers for SLE and mixed connective tissue disease.", "protein": "Anti-ribonuclear protein", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may influence immune response.", "mechanism": "Anti-Sm antibodies are highly specific for SLE diagnosis.", "protein": "Anti-Smith antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Targets nuclear glycoproteins; glycosylation may affect antigenicity.", "mechanism": "ANA positivity is a hallmark of SLE and other autoimmune diseases.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation modulates epitope exposure and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote thrombosis in antiphospholipid syndrome.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12049694" }, { "confidence": "low", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may affect antigen recognition.", "mechanism": "Anti-Jo-1 antibodies are occasionally present in SLE and other connective tissue diseases.", "protein": "Jo-1 IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12049694" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Bacterial glycoproteins may modulate host immune response via glycan-mediated interactions.", "mechanism": "H. pylori seropositivity modestly associated with increased MASLD prevalence; possible role in systemic inflammation and metabolic hormone dysregulation.", "protein": "Helicobacter pylori glycoproteins (whole-cell antigens)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049732" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylated bacterial antigens may interact with host metabolic pathways.", "mechanism": "H. pylori seropositivity modestly associated with increased obesity prevalence; may affect metabolic hormones.", "protein": "Helicobacter pylori glycoproteins (whole-cell antigens)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Possible modulation of host glycoprotein hormones.", "mechanism": "Inverse association observed in Cuban heritage; mechanism unclear.", "protein": "Helicobacter pylori glycoproteins (whole-cell antigens)", "relationship_type": "protective (in Cuban heritage)", "source_pmcid": "PMC12049732" }, { "confidence": "medium", "disease": "MASLD/NAFLD", "glycan_involvement": "CagA glycosylation may affect host cell signaling.", "mechanism": "Seropositivity for CagA associated with MASLD/NAFLD in previous studies; may increase inflammation.", "protein": "CagA", "protein_enriched": { "function": "May be necessary for the transcription, folding, export, or function of the cytotoxin", "gene_name": "cagA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55980" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049732" }, { "confidence": "medium", "disease": "MASLD/NAFLD", "glycan_involvement": "VacA glycosylation may modulate toxin activity.", "mechanism": "Seropositivity for VacA associated with MASLD/NAFLD; may promote hepatocyte injury.", "protein": "VacA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56112" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Antibodies to HyuA associated with obesity in previous studies.", "protein": "HyuA", "relationship_type": "biomarker", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Antibodies to UreA associated with diabetes in previous studies.", "protein": "UreA", "protein_enriched": { "function": "GTP hydrolase that promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis", "gene_name": "tuf", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P69952" }, "relationship_type": "biomarker", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Adiponectin is a glycoprotein; glycosylation affects secretion and function.", "mechanism": "H. pylori may alter adiponectin levels, contributing to MASLD.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "causal/modulator", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Leptin glycosylation affects stability and activity.", "mechanism": "H. pylori may regulate leptin, influencing steatotic liver disease.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal/modulator", "source_pmcid": "PMC12049732" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Ghrelin glycosylation affects hormone activity.", "mechanism": "H. pylori may regulate ghrelin, impacting liver metabolism.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "causal/modulator", "source_pmcid": "PMC12049732" }, { "confidence": "high", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "CD40L is a glycoprotein; glycosylation may affect stability and cell surface expression, but specific glycan defects not detailed.", "mechanism": "Mutations in CD40LG gene cause loss of CD40L expression/function, impairing T-B cell interaction and immunoglobulin class switch recombination.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "Pneumocystis jirovecii pneumonia (PJP)", "glycan_involvement": "Glycosylation may influence CD40L function, but not directly implicated in infection susceptibility.", "mechanism": "Defective CD40L-mediated immunity increases susceptibility to opportunistic infections like PJP.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "medium", "disease": "Autoimmune disorders", "glycan_involvement": "No direct evidence; glycosylation status may modulate immune signaling.", "mechanism": "Impaired CD40L signaling alters immune regulation, increasing risk of autoimmunity.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "medium", "disease": "Liver disorders", "glycan_involvement": "Not specified.", "mechanism": "Immune dysregulation due to CD40L deficiency predisposes to liver pathology.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "medium", "disease": "Malignant tumors", "glycan_involvement": "Not specified.", "mechanism": "Impaired immune surveillance from CD40L deficiency increases cancer risk.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "Glycosylation may affect detection by flow cytometry.", "mechanism": "Absent CD40L expression on activated CD4+ T cells is a diagnostic biomarker for X-HIGM.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "biomarker", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "Restoration of glycoprotein structure/function may be required.", "mechanism": "Gene therapy targeting CD40LG is a potential curative approach for X-HIGM.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "Mutation may alter glycosylation sites or protein folding.", "mechanism": "Mutation in exon 5 (c.505_506del; p.Y169Lfs*31) disrupts TNF-homology domain, abolishing CD40 binding and function.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "Glycosylation may affect protein stability and cell surface localization.", "mechanism": "Loss of CD40L impairs B cell memory formation and immunoglobulin class switching.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "medium", "disease": "X-linked hyper-IgM syndrome (X-HIGM)", "glycan_involvement": "Not specified.", "mechanism": "CD40L deficiency leads to abnormal T cell memory subset distribution (\u2191TCM, \u2193TEM), affecting immune response.", "protein": "CD40 ligand (CD40L, CD154, gp39)", "relationship_type": "causal", "source_pmcid": "PMC12049815" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation modulates IL-6 stability and secretion.", "mechanism": "Elevated IL-6 levels indicate liver inflammation and progression of MASH.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12050042" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation affects TNF-\u03b1 receptor binding and activity.", "mechanism": "TNF-\u03b1 promotes hepatocyte apoptosis and inflammation in MASH.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12050042" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation required for IL-1\u03b2 secretion.", "mechanism": "IL-1\u03b2 drives inflammatory cell infiltration and liver injury.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12050042" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Potential N-glycosylation regulates enzyme activity.", "mechanism": "iNOS expression marks M1 macrophage activation and oxidative stress.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "biomarker", "source_pmcid": "PMC12050042" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Possible O-glycosylation modulates nuclear localization.", "mechanism": "SREBP1 upregulation increases lipid synthesis and steatosis.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12050042" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Potential N-glycosylation affects receptor function.", "mechanism": "PPAR\u03b3 promotes adipogenesis and lipid accumulation in hepatocytes.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12050042" }, { "confidence": "high", "disease": "Macrophage activation", "glycan_involvement": "Heavily glycosylated; glycosylation required for cell surface expression.", "mechanism": "F4/80 marks macrophage infiltration in inflamed liver.", "protein": "F4/80 (EMR1)", "protein_enriched": { "function": "Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development", "gene_name": "Adgre1", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q61549" }, "relationship_type": "biomarker", "source_pmcid": "PMC12050042" }, { "confidence": "high", "disease": "Macrophage activation", "glycan_involvement": "Extensive N-glycosylation required for ligand binding.", "mechanism": "CD206 marks M2 (anti-inflammatory) macrophages; increased in resolution of inflammation.", "protein": "CD206 (MRC1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12050042" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation may affect enzyme stability.", "mechanism": "FASN catalyzes fatty acid synthesis, contributing to lipid accumulation.", "protein": "FASN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12050042" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation may modulate activity.", "mechanism": "ACC regulates fatty acid synthesis, promoting steatosis.", "protein": "ACC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12050042" }, { "confidence": "high", "disease": "Intestinal Dysfunction", "glycan_involvement": "Glycosylation may affect HSP70 stability and localization.", "mechanism": "Stabilizes actin cytoskeleton and tight junctions, preventing heat-induced barrier disruption.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "protective", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Liver Injury", "glycan_involvement": "Glycosylation may modulate chaperone activity.", "mechanism": "Upregulation prevents hepatocyte degeneration and dysfunction under heat stress.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "protective", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Oxidative Stress/Apoptosis", "glycan_involvement": "Glycosylation may regulate HSP90 function.", "mechanism": "Prevents ROS production and apoptosis by activating Akt/PKM2 and inhibiting mitochondrial calcium overload.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "protective", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Liver Injury", "glycan_involvement": "Late glycosylation end product receptor (RAGE) interaction is glycan-dependent.", "mechanism": "Activates NLRP3 inflammasome via TLR4 and RAGE signaling, leading to hepatocyte pyroptosis.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Intestinal Dysfunction", "glycan_involvement": "N-glycosylation of occludin is critical for junctional localization.", "mechanism": "HSF1-induced occludin expression improves tight junction integrity under heat stress.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12079015" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "Glycosylation may affect inflammasome assembly.", "mechanism": "Activation leads to IL-1\u03b2-mediated pyroptosis and severe liver injury under heat stress.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12079015" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "PARP-1 glycosylation may affect DNA binding.", "mechanism": "Inhibition reduces liver injury; interacts with HSP70 promoter to regulate stress response.", "protein": "PARP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Elevated in brain tissue after heat stress, correlates with neuronal damage.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for maturation and secretion.", "mechanism": "Upregulated via NLRP3 inflammasome activation in microglia after heat stress.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Liver Injury", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interaction.", "mechanism": "Secreted by Kupffer cells, drives inflammatory response and hepatocyte death under heat stress.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12079015" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Promotes activation of hepatic stellate cells and ECM deposition via Smad2/3 signaling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12122303" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Indirect; not glycosylated but downstream of glycoprotein TGF-\u03b21.", "mechanism": "Transduces TGF-\u03b21 signal to promote fibrogenic gene expression.", "protein": "SMAD3", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84022" }, "relationship_type": "causal", "source_pmcid": "PMC12122303" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen glycosylation affects fibril formation.", "mechanism": "Major ECM component upregulated during fibrosis.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Limited; minor O-glycosylation possible.", "mechanism": "Marker of activated hepatic stellate cells.", "protein": "Alpha-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Glycosylation modulates junctional localization.", "mechanism": "Maintains tight junction integrity; reduced in fibrosis.", "protein": "ZO-1 (TJP1)", "relationship_type": "protective", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Glycosylation regulates function and stability.", "mechanism": "Essential for tight junctions; loss leads to barrier leakiness.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Cholestatic liver disease", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "Exports bile acids; upregulated by DMDD to restore bile acid homeostasis.", "protein": "BSEP (ABCB11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "Glycosylation affects receptor binding.", "mechanism": "Chronic activation promotes carcinogenesis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "Fibrosis-induced vascular remodeling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12122303" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Progressive fibrosis impairs liver function.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12122303" }, { "confidence": "high", "disease": "Preserved Ratio Impaired Spirometry (PRISm)", "glycan_involvement": "Insulin is glycosylated; altered glycosylation may affect receptor binding and signaling.", "mechanism": "Insulin resistance impairs glucose uptake, leading to systemic inflammation and lung tissue remodeling.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Preserved Ratio Impaired Spirometry (PRISm)", "glycan_involvement": "Adiponectin is heavily glycosylated; glycosylation is essential for its anti-inflammatory function.", "mechanism": "Adiponectin suppresses pulmonary inflammation by inhibiting TNF-\u03b1, IL-6, and chemokine production.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Preserved Ratio Impaired Spirometry (PRISm)", "glycan_involvement": "Resistin glycosylation modulates its secretion and activity.", "mechanism": "Resistin promotes inflammation and is linked to asthma, COPD, fibrosis, and acute lung injury.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Preserved Ratio Impaired Spirometry (PRISm)", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interaction.", "mechanism": "TNF-\u03b1 mediates systemic and airway inflammation, contributing to lung function decline.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Preserved Ratio Impaired Spirometry (PRISm)", "glycan_involvement": "IL-6 glycosylation influences secretion and bioactivity.", "mechanism": "IL-6 promotes chronic inflammation and airway remodeling in insulin resistance.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycation (non-enzymatic glycosylation) of hemoglobin is the basis for HbA1c measurement.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used in eGDR calculation.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for adiponectin multimerization and function.", "mechanism": "Low adiponectin in obesity increases inflammation and risk of lung dysfunction.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects resistin's pro-inflammatory activity.", "mechanism": "Resistin is upregulated in obesity, promoting insulin resistance and inflammation.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation modulates TNF-\u03b1's inflammatory signaling.", "mechanism": "TNF-\u03b1 induces insulin resistance and is elevated in diabetes.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation regulates IL-6 secretion and activity.", "mechanism": "IL-6 contributes to insulin resistance and metabolic dysfunction.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12122331" }, { "confidence": "medium", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation affects folate-binding protein stability and transport efficiency.", "mechanism": "Folate competes with phthalates for transporter binding, reducing phthalate absorption and burden.", "protein": "Folate-binding protein", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "medium", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation modulates transporter localization and substrate specificity.", "mechanism": "Folate and phthalates share SLC transporters; increased folate may reduce phthalate uptake.", "protein": "Solute carrier transporters (SLCs)", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "medium", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation regulates ABC transporter trafficking and function.", "mechanism": "Folate may compete with phthalates for ABC transporter-mediated excretion.", "protein": "ATP-binding cassette transporters (ABCs)", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "medium", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation influences OAT stability and substrate affinity.", "mechanism": "Folate competes with phthalates for OAT-mediated renal reabsorption, lowering phthalate levels.", "protein": "Organic anion transporters (OATs)", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "medium", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation affects lipase secretion and activity.", "mechanism": "Lipase hydrolyzes phthalates to monoester metabolites; folate reduces lipase expression via methylation.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "causal", "source_pmcid": "PMC12122348" }, { "confidence": "low", "disease": "Reproductive toxicity", "glycan_involvement": "Glycosylation required for folate-binding protein function in reproductive tissues.", "mechanism": "Folate supplementation mitigates phthalate-induced reproductive toxicity.", "protein": "Folate-binding protein", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "low", "disease": "Neurotoxicity", "glycan_involvement": "Glycosylation influences CNS folate transport.", "mechanism": "Folate may reduce phthalate-induced neurotoxicity via improved methylation and reduced phthalate burden.", "protein": "Folate-binding protein", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects vascular folate transport.", "mechanism": "Folate reduces phthalate burden, potentially lowering cardiovascular risk.", "protein": "Folate-binding protein", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "low", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation modulates folate transport in lung tissue.", "mechanism": "Folate may mitigate phthalate-induced respiratory effects.", "protein": "Folate-binding protein", "relationship_type": "protective", "source_pmcid": "PMC12122348" }, { "confidence": "low", "disease": "Phthalate toxicity", "glycan_involvement": "Glycosylation impacts lipase activity and stability.", "mechanism": "Targeting lipase activity may reduce phthalate metabolite formation.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122348" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-glycosylation required for P-selectin binding.", "mechanism": "Platelet-derived P-selectin binds PSGL-1 on TAMs, activating C5a/C5aR1 axis and promoting tumor growth/metastasis.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122509" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation affects ligand binding and scavenging function.", "mechanism": "M2c TAMs expressing CD163 promote immunosuppression and matrix remodeling.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Mannose-rich glycosylation mediates ligand recognition.", "mechanism": "LOXL2+ CAFs correlate with CD206+ M2 TAMs, predicting poor prognosis and immunotherapy response.", "protein": "CD206", "relationship_type": "biomarker", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Sialic acid binding via glycosylated ligands.", "mechanism": "NK cell-derived IFN-\u03b3 induces CD169+ TAMs, promoting anti-tumor immunity.", "protein": "Siglec-1 (CD169)", "relationship_type": "protective", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1+ TAMs at tumor margins suppress T cell activity; anti-PD-L1 therapy depletes these macrophages.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Prostate cancer (PCa)", "glycan_involvement": "Glycosylation modulates receptor interactions.", "mechanism": "SPP1+ TAMs inhibit CD8+ T cells via adenosine signaling, promoting immunosuppression.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12122509" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation required for adhesion function.", "mechanism": "CAF-induced VCAM-1 upregulation recruits monocytes and promotes M2 TAM polarization.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12122509" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation may affect enzyme stability and ECM remodeling.", "mechanism": "LOXL2+ CAFs induce CD206+ M2 TAMs, associated with poor prognosis and immunotherapy resistance.", "protein": "LOXL2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12122509" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Predicted glycosylation may affect membrane localization.", "mechanism": "MS4A4A+ TAMs linked to poor outcomes; anti-MS4A4A therapy effective in refractory CRC.", "protein": "MS4A4A", "protein_enriched": { "function": "Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, a", "gene_name": "DCHS1", "glycan_count": 16, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00912UN", "G08918WF", "G45395BF", "G02815KT", "G08290VR", "G31852PQ", "G31986NC", "G41247ZX", "G47644PP", "G80920RR", "G40574BA", "G27058EU", "G01650EU", "G28541PG", "G41840AI", "G59924QI" ], "uniprot_id": "Q96JQ0" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of Fc\u03b3R and IgG modulates binding and signaling.", "mechanism": "IgG from plasma cells activates Fc\u03b3R on TAMs, inducing IL-6/IL-10/CCL20 and suppressing anti-tumor immunity.", "protein": "Fc gamma receptor (Fc\u03b3R)", "relationship_type": "causal", "source_pmcid": "PMC12122509" }, { "confidence": "high", "disease": "Endometrial Cancer (EC)", "glycan_involvement": "HE4 is a secreted glycoprotein; glycosylation affects stability and detection.", "mechanism": "Highly expressed in EC; serum levels correlate with disease progression.", "protein": "HE4 (Human Epididymis Protein 4)", "protein_enriched": { "function": "Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP", "gene_name": "DNAH11", "glycan_count": 12, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G27391WQ", "G06356OH", "G20210JR", "G23294PN", "G25418HZ", "G25451PN", "G44215PV", "G48584BU", "G50045TK", "G72398FA", "G80223IX", "G84452RH" ], "uniprot_id": "Q96DT5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12122774" }, { "confidence": "high", "disease": "Endometrial Cancer (EC)", "glycan_involvement": "Heavily O-glycosylated mucin; glycosylation critical for detection and function.", "mechanism": "Elevated serum CA125 correlates with poor prognosis and advanced disease.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12122774" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune evasion.", "mechanism": "Serum CEA is a prognostic marker for CRC recurrence and progression.", "protein": "CEA (CEACAM5)", "relationship_type": "biomarker", "source_pmcid": "PMC12122774" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "N-glycosylation affects ligand binding and receptor activation.", "mechanism": "Overexpressed in CRC; targeted by anti-EGFR therapies.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12122774" }, { "confidence": "medium", "disease": "Serous Endometrial Carcinoma", "glycan_involvement": "N-glycosylation modulates receptor function and stability.", "mechanism": "Overexpression/amplification linked to poor prognosis; target for anti-HER2 therapy.", "protein": "HER2/ERBB2", "relationship_type": "prognostic_marker/therapeutic_target", "source_pmcid": "PMC12122774" }, { "confidence": "high", "disease": "Endometrial Cancer (EC)", "glycan_involvement": "Not specified.", "mechanism": "Loss (mutation or hypermethylation) leads to MMR deficiency and MSI-H EC.", "protein": "MLH1", "protein_enriched": { "function": "Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t", "gene_name": "MLH1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G42124LM", "G49108TO" ], "uniprot_id": "P40692" }, "relationship_type": "causal", "source_pmcid": "PMC12122774" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Not specified.", "mechanism": "Germline mutations cause MMR deficiency, driving CRC in LS.", "protein": "MSH2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismat", "gene_name": "MSH2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50713DU", "G21891JQ", "G49108TO" ], "uniprot_id": "P43246" }, "relationship_type": "causal", "source_pmcid": "PMC12122774" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Heavily glycosylated; glycosylation affects cell adhesion.", "mechanism": "EPCAM deletions cause epigenetic silencing of MSH2, leading to MMR deficiency and CRC.", "protein": "EPCAM", "relationship_type": "causal", "source_pmcid": "PMC12122774" }, { "confidence": "medium", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Not specified.", "mechanism": "Pathogenic variants increase CRC risk (lower than MLH1/MSH2).", "protein": "PMS2", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) o", "gene_name": "PMS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54278" }, "relationship_type": "causal", "source_pmcid": "PMC12122774" }, { "confidence": "medium", "disease": "Endometrial Cancer (EC)", "glycan_involvement": "Not specified.", "mechanism": "Pathogenic variants confer high EC risk in LS.", "protein": "MSH6", "protein_enriched": { "function": "Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha be", "gene_name": "MSH6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52701" }, "relationship_type": "causal", "source_pmcid": "PMC12122774" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation in Golgi is essential for collagen maturation and ECM deposition.", "mechanism": "Collagen degradation releases hydroxyproline, fueling cancer cell metabolism and survival.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PEPD acts on glycopeptides from collagen; glycosylation status affects substrate availability.", "mechanism": "PEPD overexpression increases intracellular proline/hydroxyproline, stabilizing HIF-1\u03b1 and promoting tumor survival.", "protein": "Prolidase (PEPD)", "protein_enriched": { "function": "Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position (PubMed:17081196, PubMed:35165443). The preferred dipeptide substrat", "gene_name": "PEPD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12955" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation in Golgi required for enzyme stability and collagen substrate recognition.", "mechanism": "P4HA2 overexpression promotes collagen hydroxylation, ECM remodeling, and tumor progression.", "protein": "Prolyl 4-hydroxylase (P4HA2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycosylation modulates enzyme activity and collagen processing.", "mechanism": "Elevated P4HA1 drives collagen deposition and supports tumor growth.", "protein": "Prolyl 4-hydroxylase (P4HA1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Indirect; acts on hydroxyproline from glycoproteins.", "mechanism": "PRODH2/OH-POX activation induces ROS-dependent apoptosis in cancer cells via hydroxyproline metabolism.", "protein": "Hydroxyproline dehydrogenase 2 (PRODH2/OH-POX)", "protein_enriched": { "function": "Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and me", "gene_name": "ABRAXAS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6UWZ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Proline hydroxylation (not glycosylation) regulates HIF-1\u03b1 degradation.", "mechanism": "Hydroxyproline stabilizes HIF-1\u03b1, promoting angiogenesis, glycolysis, and metastasis.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Angiogenesis", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "HIF-1\u03b1 upregulates VEGF, driving tumor angiogenesis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12123091" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "GLUT-1 is glycosylated; glycosylation affects membrane localization and function.", "mechanism": "HIF-1\u03b1 upregulates GLUT-1, enhancing glycolytic metabolism in tumors.", "protein": "Glucose Transporter-1 (GLUT-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12123091" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "FAK is glycosylated; glycosylation may affect stability.", "mechanism": "Cis-4-hydroxyproline induces caspase-independent FAK degradation, leading to loss of adhesion and apoptosis.", "protein": "Focal Adhesion Kinase (FAK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123091" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "C1q is heavily glycosylated; glycosylation modulates immune function.", "mechanism": "C1q, a hydroxyproline-rich glycoprotein, is involved in ECM turnover and inflammation.", "protein": "C1q complement", "relationship_type": "causal", "source_pmcid": "PMC12123091" }, { "confidence": "high", "disease": "Visceral leishmaniasis", "glycan_involvement": "Glycosylation of rk39 is essential for its antigenicity and recognition by host antibodies.", "mechanism": "rk39 antigen is a Leishmania surface glycoprotein detected in serological tests; its presence indicates active infection.", "protein": "rk39 antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12123092" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Albumin glycosylation may affect stability and clearance; decreased synthesis impacts glycoprotein pool.", "mechanism": "Hypoalbuminemia reflects impaired hepatic synthesis due to liver damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Hepatitis", "glycan_involvement": "Altered glycosylation may affect albumin function and distribution.", "mechanism": "Reduced albumin levels indicate hepatocellular dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Biliary disorders", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects membrane localization and activity.", "mechanism": "Elevated ALP indicates cholestasis and biliary epithelial injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "GGT glycosylation modulates enzyme activity and stability.", "mechanism": "Increased GGT reflects biliary tract damage and hepatocyte membrane injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Includes multiple glycoproteins; overall decrease reflects reduced glycoprotein synthesis.", "mechanism": "Reduced total protein indicates impaired hepatic synthetic function.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "medium", "disease": "Neoplastic disorders", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects immune response.", "mechanism": "Elevated globulin levels suggest increased immunoglobulin production or inflammation.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Hepatitis", "glycan_involvement": "Glycosylation influences ALP activity and secretion.", "mechanism": "ALP elevation reflects hepatocyte and biliary tract injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Hepatitis", "glycan_involvement": "Glycosylation modulates GGT function.", "mechanism": "Elevated GGT is associated with hepatocellular and biliary damage.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Ascites (secondary to hepatobiliary disease)", "glycan_involvement": "Glycosylation may affect albumin's oncotic properties.", "mechanism": "Low albumin reduces plasma oncotic pressure, leading to fluid accumulation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "Jaundice (secondary to hepatobiliary disease)", "glycan_involvement": "Bilirubin binds to glycoproteins for transport; altered glycosylation may affect clearance.", "mechanism": "Elevated bilirubin indicates impaired hepatic clearance and excretion.", "protein": "Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC12123276" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "hs-CRP is a heavily glycosylated protein; glycosylation affects its stability and immune function.", "mechanism": "hs-CRP levels reflect systemic inflammation and are elevated in MASLD, mediating disease risk.", "protein": "high-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12123378" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "N-glycosylation modulates CRP's activity and clearance.", "mechanism": "hs-CRP predicts NAFLD risk and progression via inflammatory pathways.", "protein": "high-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes hepatic inflammation and steatosis in MASLD.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation modulates IL-6 stability and signaling.", "mechanism": "IL-6 drives chronic inflammation and metabolic dysfunction in MASLD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Microbial glycoproteins interact with host mucins and immune receptors.", "mechanism": "Fermented dairy increases Lactobacillus, whose glycoproteins help restore gut barrier and reduce liver inflammation.", "protein": "Lactobacillus-derived glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Microbial glycoproteins modulate host immune responses.", "mechanism": "Chickpeas and soybeans promote Bifidobacteria, whose glycoproteins support gut health and reduce MASLD risk.", "protein": "Bifidobacteria-derived glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12123378" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation influences CRP's inflammatory activity.", "mechanism": "hs-CRP is elevated in obesity, reflecting chronic low-grade inflammation.", "protein": "high-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12123378" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation is essential for CRP's solubility and immune function.", "mechanism": "hs-CRP is a marker of systemic inflammation, which mediates MASLD progression.", "protein": "high-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells.", "mechanism": "Elevated hs-CRP is associated with increased diabetes risk and metabolic dysfunction.", "protein": "high-sensitivity C-reactive protein (hs-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12123378" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation affects IL-6 receptor binding and signaling.", "mechanism": "IL-6 drives systemic inflammation, contributing to MASLD and metabolic syndrome.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12123378" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Overexpression increases intestinal glucose absorption and contributes to hyperglycemia.", "protein": "SGLT1", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a tr", "gene_name": "SLC5A1", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G49108TO" ], "uniprot_id": "P13866" }, "relationship_type": "causal", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects trafficking and stability.", "mechanism": "Overexpression facilitates increased glucose transport into circulation, exacerbating hyperglycemia.", "protein": "GLUT2", "protein_enriched": { "function": "Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "causal", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-glycosylation modulates peptide stability.", "mechanism": "Reduced levels in diabetes; restoration improves insulin secretion and \u03b2-cell survival.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "O-glycosylation affects hormone activity.", "mechanism": "Reduced levels in diabetes; restoration enhances insulin secretion.", "protein": "GIP", "relationship_type": "protective", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "N-glycosylation required for enzymatic activity and membrane localization.", "mechanism": "DPP4 degrades GLP-1/GIP; inhibition increases incretin half-life and insulinotropic effect.", "protein": "DPP4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation not directly involved, but folding and secretion depend on ER glycoprotein machinery.", "mechanism": "Reduced secretion in diabetes; restoration indicates improved \u03b2-cell function.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12123729" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation affects secretion and lipid binding.", "mechanism": "Elevated in diabetes due to increased VLDL secretion.", "protein": "ApoB", "relationship_type": "biomarker", "source_pmcid": "PMC12123729" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation required for enzyme activity.", "mechanism": "Reduced activity in insulin resistance leads to impaired triglyceride clearance.", "protein": "Lipoprotein lipase", "relationship_type": "causal", "source_pmcid": "PMC12123729" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "Elevated in diabetes/NAFLD indicating hepatocellular injury.", "protein": "ALT (GPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12123729" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "Elevated in diabetes/NAFLD indicating liver injury.", "protein": "AST (GOT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12123729" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "Elevated xanthine oxidase activity increases uric acid synthesis, contributing to hyperuricemia.", "protein": "Xanthine oxidase", "relationship_type": "causal", "source_pmcid": "PMC12124120" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Increased uric acid production by xanthine oxidase leads to urate crystal deposition and gout.", "protein": "Xanthine oxidase", "relationship_type": "causal", "source_pmcid": "PMC12124120" }, { "confidence": "medium", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation may affect HGPRT folding and activity.", "mechanism": "HGPRT mutations (possibly induced by smoking) decrease purine salvage, increasing uric acid.", "protein": "HGPRT", "relationship_type": "causal", "source_pmcid": "PMC12124120" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Glycosylation status may influence enzyme stability.", "mechanism": "HGPRT deficiency increases uric acid, predisposing to gout.", "protein": "HGPRT", "relationship_type": "causal", "source_pmcid": "PMC12124120" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may affect enzyme secretion and activity.", "mechanism": "Elevated xanthine oxidase activity increases reactive oxygen species, contributing to vascular damage.", "protein": "Xanthine oxidase", "relationship_type": "biomarker", "source_pmcid": "PMC12124120" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may modulate enzyme function.", "mechanism": "Hyperuricemia is a risk factor for diabetes; xanthine oxidase activity is linked to uric acid levels.", "protein": "Xanthine oxidase", "relationship_type": "biomarker", "source_pmcid": "PMC12124120" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation affects protein stability and ligand binding.", "mechanism": "Transports 25(OH)D, influencing muscle health and sarcopenia risk.", "protein": "Vitamin D Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may alter circulatory half-life and receptor interactions.", "mechanism": "Modulates bioavailability of 25(OH)D, impacting CVD risk.", "protein": "Vitamin D Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation influences albumin's antioxidant and transport functions.", "mechanism": "Reflects nutritional and inflammatory status, associated with mortality risk.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation (not classical glycosylation) marks disease severity.", "mechanism": "Indicates chronic hyperglycemia, linked to diabetes and related mortality.", "protein": "Glycohemoglobin (Hemoglobin A1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect immune modulation and tumor microenvironment.", "mechanism": "Regulates 25(OH)D levels, which may influence cancer risk and progression.", "protein": "Vitamin D Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation modulates vascular protection and anti-inflammatory properties.", "mechanism": "Low albumin associated with increased CVD risk and mortality.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect neuroprotective functions.", "mechanism": "Low 25(OH)D (carried by DBP) linked to higher stroke risk.", "protein": "Vitamin D Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation of apolipoproteins affects HDL function.", "mechanism": "HDL-C levels inversely associated with CVD risk.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation may impact vascular interactions.", "mechanism": "DBP modulates 25(OH)D bioavailability, influencing CHD risk.", "protein": "Vitamin D Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation affects muscle repair and systemic inflammation.", "mechanism": "Low albumin reflects poor nutritional status, associated with sarcopenia.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12124123" }, { "confidence": "high", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "Glycosylation of IL-6R affects ligand binding and receptor clearance.", "mechanism": "IL-6R blockade by TCZ reduces inflammation, DSA production, and microvascular injury.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Microvascular inflammation (MVI)", "glycan_involvement": "IL-6 glycosylation affects stability and secretion.", "mechanism": "IL-6 promotes B/T cell activation, antibody production, and endothelial activation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Kidney graft failure", "glycan_involvement": "IgG glycosylation modulates effector function and complement activation.", "mechanism": "DSA presence and MFI correlate with risk of graft failure and caAMR.", "protein": "Donor-specific anti-HLA antibodies (DSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "C4d is a glycoprotein fragment deposited in tissue.", "mechanism": "C4d deposition indicates complement activation by DSA.", "protein": "C4d", "relationship_type": "biomarker", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "TCZ is a glycosylated monoclonal antibody; glycosylation affects pharmacokinetics.", "mechanism": "TCZ blocks IL-6R, reducing DSA, microvascular inflammation, and stabilizing renal function.", "protein": "Tocilizumab (TCZ)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124137" }, { "confidence": "medium", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "Glycosylation affects antibody stability and immune modulation.", "mechanism": "Clazakizumab (anti-IL-6) reduces DSA MFI and slows eGFR decline.", "protein": "Clazakizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124137" }, { "confidence": "medium", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "CD38 glycosylation modulates cell surface expression and antibody binding.", "mechanism": "Anti-CD38 antibody depletes plasma cells, reducing DSA and inflammation.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Kidney graft failure", "glycan_involvement": "Fc glycosylation regulates effector functions and complement activation.", "mechanism": "IgG DSA mediate complement activation and endothelial injury.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12124137" }, { "confidence": "medium", "disease": "Chronic-active antibody-mediated rejection (caAMR)", "glycan_involvement": "C3 glycosylation affects activation and deposition.", "mechanism": "C3 activation is part of complement cascade triggered by DSA.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates receptor function and antibody binding.", "mechanism": "TCZ blocks IL-6R, reducing inflammation and disease activity.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124137" }, { "confidence": "high", "disease": "Skin wound healing", "glycan_involvement": "Glycosylation required for stability and receptor binding.", "mechanism": "Promotes keratinocyte proliferation, migration, and differentiation via FGFR2 IIIb signaling; regulates inflammatory response and tissue healing phases.", "protein": "KGF-2 / FGF-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124295" }, { "confidence": "high", "disease": "Scar formation", "glycan_involvement": "Glycosylation may modulate anti-fibrotic activity.", "mechanism": "Inhibits STAP-2 and STAT3 activation, reduces collagen I/III, thereby reducing scar formation during wound healing.", "protein": "KGF-2 / FGF-10", "relationship_type": "protective", "source_pmcid": "PMC12124295" }, { "confidence": "high", "disease": "Corneal injury", "glycan_involvement": "Glycosylation enhances protein stability and bioactivity.", "mechanism": "Accelerates corneal epithelial regeneration, migration, and reduces inflammation and scar formation.", "protein": "KGF-2 / FGF-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124295" }, { "confidence": "medium", "disease": "Cataract", "glycan_involvement": "Glycosylation may affect cellular uptake and signaling.", "mechanism": "Regulates Nrf2/PI3K/Akt pathways, reduces oxidative stress and apoptosis in lens epithelial cells.", "protein": "KGF-2 / FGF-10", "relationship_type": "protective", "source_pmcid": "PMC12124295" }, { "confidence": "high", "disease": "Hair loss (Alopecia)", "glycan_involvement": "Glycosylation required for receptor interaction and follicle stimulation.", "mechanism": "Promotes hair follicle cell proliferation and migration, induces anagen phase via Wnt/\u03b2-catenin and SHH pathways.", "protein": "KGF-2 / FGF-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124295" }, { "confidence": "high", "disease": "Skin wound healing", "glycan_involvement": "Glycosylation critical for receptor binding and activity.", "mechanism": "Promotes epidermal cell proliferation and migration; transdermal fusion with TD1 enhances delivery.", "protein": "EGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124295" }, { "confidence": "medium", "disease": "Hair loss (Alopecia)", "glycan_involvement": "SHH is a secreted glycoprotein; glycosylation essential for signaling.", "mechanism": "Regulates hair follicle cycling, promotes transition from telogen to anagen.", "protein": "SHH", "relationship_type": "causal", "source_pmcid": "PMC12124295" }, { "confidence": "medium", "disease": "Hair loss (Alopecia)", "glycan_involvement": "Glycosylation affects stability and receptor interaction.", "mechanism": "Induces hair growth via dermal papilla cell stimulation.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12124295" }, { "confidence": "medium", "disease": "Hair loss (Alopecia)", "glycan_involvement": "Glycosylation required for secretion and angiogenic activity.", "mechanism": "Promotes vascularization and hair follicle growth.", "protein": "VEGF", "relationship_type": "protective", "source_pmcid": "PMC12124295" }, { "confidence": "medium", "disease": "Hair loss (Alopecia)", "glycan_involvement": "Glycosylation modulates receptor binding and activity.", "mechanism": "Stimulates hair follicle growth and dermal papilla cell proliferation.", "protein": "HGF", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01543ZX", "G11629QQ", "G17689DH", "G22310AV", "G48414YA", "G52126RR", "G52527GH", "G57789QC", "G60542VK", "G64394MX", "G74239ZQ", "G77252PU", "G89664KV", "G93656SY", "G45637XA", "G81006GJ", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G40834TG", "G41071NU", "G42124LM", "G45395BF", "G86880BF", "G90659AW", "G41247ZX", "G46691LC", "G62765YT", "G80920RR", "G83460ZZ" ], "uniprot_id": "P14210" }, "relationship_type": "protective", "source_pmcid": "PMC12124295" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation required for receptor function and immune modulation", "mechanism": "Promotes proliferation, migration, invasion; regulates immune infiltration (NK cells, M0 macrophages)", "protein": "MERTK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target/biomarker", "source_pmcid": "PMC12124307" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation affects anti-angiogenic activity", "mechanism": "Inhibits migration and invasion; high expression improves survival (OS, DSS, PFI); modulates chromosomal activity and innate immunity", "protein": "SERPINF1", "relationship_type": "protective/biomarker/therapeutic_target", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation modulates IgG binding and immune cell interactions", "mechanism": "Associated with immune infiltration; risk factor for cervical cancer", "protein": "FCGR3B", "protein_enriched": { "function": "Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cy", "gene_name": "FCGR3B", "glycan_count": 40, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G60177UT", "G82830MN", "G03382KH", "G05724UK", "G06110VR", "G17689DH", "G22310AV", "G23432EQ", "G23863VK", "G25520XG", "G26915XM", "G29011JC", "G31916IQ", "G31936TA", "G39188ZX", "G39213VZ", "G46687AB", "G49874UX", "G55220VL", "G60145BJ", "G62326NX", "G62389NM", "G63381RX", "G64527OM", "G70418MS", "G72291OX", "G72667IM", "G72797UR", "G72902CL", "G74430RZ", "G78059CC", "G80858MF", "G82119TF", "G84452RH", "G90093AU", "G90717TP", "G91636VS", "G93141AZ", "G96095QD", "G96771UL" ], "uniprot_id": "O75015" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Cell surface glycoprotein; glycosylation influences immune recognition", "mechanism": "Activated by HPV; risk factor for cervical cancer", "protein": "BTN3A3", "protein_enriched": { "function": "", "gene_name": "BTN2A1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41891LD", "G22573RC", "G26436YP", "G98129XB", "G49108TO" ], "uniprot_id": "Q7KYR7" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation required for transporter stability and function", "mechanism": "Involved in antigen presentation; positively correlated with immune cell infiltration", "protein": "TAP2", "protein_enriched": { "function": "ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class", "gene_name": "TAP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q03518" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Serpin glycoprotein; glycosylation affects inhibitory activity", "mechanism": "Downregulated; protective effect via immune modulation (monocytes, macrophages)", "protein": "SERPINE2", "protein_enriched": { "function": "Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin", "gene_name": "SERPINE2", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G14972EH", "G27058EU", "G30740WO", "G34989PA", "G40574BA", "G41071NU", "G45395BF", "G83460ZZ", "G87661QW", "G49108TO", "G80920RR", "G43417UB" ], "uniprot_id": "P07093" }, "relationship_type": "protective", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Cadherin glycoprotein; glycosylation modulates cell adhesion", "mechanism": "Upregulated; promotes immune cell infiltration (macrophages M0, NK cells)", "protein": "CELSR3", "relationship_type": "causal", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation required for transporter activity", "mechanism": "Upregulated; involved in amino acid transport and immune cell infiltration", "protein": "SLC1A5", "relationship_type": "causal", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation may affect protein stability", "mechanism": "Upregulated; associated with immune cell infiltration (Tfhs, dendritic cells)", "protein": "SMG5", "relationship_type": "causal", "source_pmcid": "PMC12124307" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation modulates receptor function", "mechanism": "Downregulated; protective effect, interacts with other glycoproteins", "protein": "GABBR1", "relationship_type": "protective", "source_pmcid": "PMC12124307" }, { "confidence": "high", "disease": "Acute liver injury (ALI)", "glycan_involvement": "FGF21 is a secreted glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Serum FGF21 is elevated early in ALI and predicts its onset in critically ill patients with bacterial infections.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "high", "disease": "Sepsis-associated liver injury", "glycan_involvement": "Glycosylation may influence FGF21's circulatory half-life and receptor interactions.", "mechanism": "FGF21 suppresses inflammatory cascades and protects against sepsis-induced liver injury.", "protein": "Fibroblast growth factor 21", "relationship_type": "protective", "source_pmcid": "PMC12124309" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "Therapeutic analogues may be glycoengineered for improved efficacy.", "mechanism": "FGF21 analogues improve hepatic outcomes in MASH patients.", "protein": "Fibroblast growth factor 21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Acute hepatitis B", "glycan_involvement": "Glycosylation status not specified but may affect detection.", "mechanism": "FGF21 correlates with liver injury severity and normalizes after treatment.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Glycosylation may be altered in chronic liver disease.", "mechanism": "FGF21 levels are reduced, reflecting impaired hepatic synthesis.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation may affect FGF21 levels in cirrhosis.", "mechanism": "FGF21 is elevated in early cirrhosis but reduced in advanced disease.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may impact FGF21's diagnostic utility.", "mechanism": "FGF21 is elevated and may serve as an early diagnostic marker.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect FGF21's serum stability.", "mechanism": "FGF21 is elevated in NAFLD and may aid diagnosis.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Mitochondrial disease", "glycan_involvement": "Glycosylation may influence FGF21's diagnostic performance.", "mechanism": "FGF21 identifies primary muscle-manifesting respiratory chain deficiencies.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "medium", "disease": "Acute liver injury (ALI)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects its stability and function.", "mechanism": "Serum albumin is negatively correlated with FGF21 in ALI, reflecting impaired hepatic synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124309" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Heavy O-glycosylation, especially sialic acid content, affects barrier function and nutrient sensing.", "mechanism": "Altered mucin glycosylation and duodenal mucus barrier properties contribute to duodenal dysfunction and impaired glucose homeostasis.", "protein": "Mucin (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC12124365" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation patterns modulate mucus permeability and epithelial signaling.", "mechanism": "Diet-induced changes in mucin glycosylation and duodenal mucus barrier properties are associated with obesity pathogenesis.", "protein": "Mucin (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC12124365" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "GLY-200 binds sialic acid residues on O-glycans of mucin via boronic acid chemistry.", "mechanism": "GLY-200 drug complexes with mucin glycoproteins, enhancing duodenal mucus barrier and mimicking duodenal exclusion, improving glycemia.", "protein": "Mucin (MUC2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124365" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Targeting mucin O-glycans alters nutrient sensing and gut hormone release.", "mechanism": "GLY-200 complexation with mucin reduces body weight and visceral adiposity in animal models.", "protein": "Mucin (MUC2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "GLP-1 is a glycoprotein; secretion is modulated by mucin barrier properties.", "mechanism": "Duodenal exclusion (via mucin complexation) increases GLP-1 secretion, improving glycemic control.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Indirect; mucin glycosylation affects GLP-1 cell stimulation.", "mechanism": "Enhanced GLP-1 release after mucin complexation reduces appetite and body weight.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Indirect; mucin barrier modulation affects enteroendocrine cell function.", "mechanism": "Duodenal exclusion increases PYY, contributing to improved glycemic control.", "protein": "PYY", "relationship_type": "protective", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Indirect; mucin glycosylation influences hormone release.", "mechanism": "Increased PYY after mucin complexation reduces appetite and weight gain.", "protein": "PYY", "relationship_type": "protective", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Changes in O-glycosylation and sialylation status.", "mechanism": "Altered mucin glycosylation and duodenal mucus properties are associated with T2D pathology.", "protein": "Mucin (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC12124365" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Altered O-glycan structures affect barrier and signaling.", "mechanism": "Duodenal mucin glycosylation changes correlate with obesity and metabolic dysfunction.", "protein": "Mucin (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC12124365" }, { "confidence": "high", "disease": "Kidney transplant rejection", "glycan_involvement": "Tacrolimus binds to FKBP12, affecting glycoprotein-mediated T-cell signaling.", "mechanism": "Tacrolimus suppresses T-cell activation to prevent rejection.", "protein": "Tacrolimus (FK506)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124500" }, { "confidence": "high", "disease": "Tacrolimus toxicity", "glycan_involvement": "Tacrolimus transport and metabolism involve glycoproteins (P-glycoprotein).", "mechanism": "CYP3A inhibition by ritonavir increases tacrolimus levels, causing toxicity.", "protein": "Tacrolimus (FK506)", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Tacrolimus modulates immune glycoprotein signaling.", "mechanism": "Immunosuppression may reduce risk of acute rejection during COVID-19 infection.", "protein": "Tacrolimus (FK506)", "relationship_type": "protective", "source_pmcid": "PMC12124500" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N protein is glycosylated, affecting immune recognition.", "mechanism": "N protein detected by RT-PCR for COVID-19 diagnosis.", "protein": "SARS-CoV-2 nucleocapsid protein (N)", "relationship_type": "biomarker", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "Tacrolimus toxicity", "glycan_involvement": "P-glycoprotein glycosylation affects drug transport.", "mechanism": "Ritonavir inhibits P-glycoprotein, increasing tacrolimus absorption.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "Opportunistic infections (CMV)", "glycan_involvement": "CMV glycoproteins mediate cell entry and immune evasion.", "mechanism": "Immunosuppression increases risk of CMV infection.", "protein": "Cytomegalovirus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "Opportunistic infections (Herpes)", "glycan_involvement": "Herpesvirus glycoproteins facilitate host cell entry.", "mechanism": "Immunosuppression increases risk of herpesvirus infection.", "protein": "Herpesvirus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "Creatinine elevation", "glycan_involvement": "Tacrolimus impacts glycoprotein-mediated renal signaling.", "mechanism": "Elevated tacrolimus levels cause nephrotoxicity.", "protein": "Tacrolimus (FK506)", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "Opportunistic infections (PJP, CMV, Herpes)", "glycan_involvement": "Tacrolimus affects immune glycoprotein function.", "mechanism": "Excess immunosuppression increases infection risk.", "protein": "Tacrolimus (FK506)", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "medium", "disease": "COVID-19 recurrence", "glycan_involvement": "Tacrolimus modulates immune glycoprotein pathways.", "mechanism": "Improper tacrolimus dosing delays viral clearance, increasing recurrence risk.", "protein": "Tacrolimus (FK506)", "relationship_type": "causal", "source_pmcid": "PMC12124500" }, { "confidence": "high", "disease": "Acute liver injury (ALI)", "glycan_involvement": "ALT is glycosylated, which may affect its stability and clearance.", "mechanism": "ALT is released into circulation upon hepatocyte injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "high", "disease": "Acute liver injury (ALI)", "glycan_involvement": "AST glycosylation may influence its serum half-life.", "mechanism": "AST is released into circulation upon hepatocyte injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "high", "disease": "Acute liver injury (ALI)", "glycan_involvement": "ALP glycosylation affects its tissue localization and activity.", "mechanism": "ALP increases in cholestatic and mixed liver injury.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "medium", "disease": "Acute liver injury (ALI)", "glycan_involvement": "GGT glycosylation modulates its membrane association.", "mechanism": "GGT is elevated in cholestatic liver injury.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "medium", "disease": "Acute liver injury (ALI)", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion and function.", "mechanism": "Prothrombin activity reflects hepatic synthetic function.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "high", "disease": "Acute liver injury (ALI)", "glycan_involvement": "Not applicable (miRNA, not glycoprotein).", "mechanism": "miRNA122 is released from damaged hepatocytes and is highly liver-specific.", "protein": "miRNA122", "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Not applicable.", "mechanism": "Elevated miRNA122 indicates hepatocyte injury from drugs.", "protein": "miRNA122", "relationship_type": "biomarker", "source_pmcid": "PMC12124506" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not applicable.", "mechanism": "Knockdown of miRNA122 promotes HCC development; normal levels are protective.", "protein": "miRNA122", "relationship_type": "causal/protective", "source_pmcid": "PMC12124506" }, { "confidence": "medium", "disease": "Steatohepatitis", "glycan_involvement": "Not applicable.", "mechanism": "Loss of miRNA122 promotes steatohepatitis and fibrosis.", "protein": "miRNA122", "relationship_type": "causal/protective", "source_pmcid": "PMC12124506" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Not applicable.", "mechanism": "Knockdown of miRNA122 promotes fibrosis in mouse models.", "protein": "miRNA122", "relationship_type": "causal/protective", "source_pmcid": "PMC12124506" }, { "confidence": "high", "disease": "Microbial contamination/foodborne illness", "glycan_involvement": "Glycosylation of lactoferrin is essential for its antimicrobial function and stability.", "mechanism": "Lactoferrin exhibits antimicrobial activity, inhibiting microbial growth in food products.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12124640" }, { "confidence": "medium", "disease": "Lipid oxidation-related diseases (e.g., gastric cancer, liver cancer, cardiovascular diseases)", "glycan_involvement": "Glycosylation modulates lactoferrin's antioxidant activity.", "mechanism": "Lactoferrin has antioxidant properties, reducing lipid oxidation and formation of harmful peroxides.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12124640" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation affects lactoferrin's stability and bioactivity in food matrices.", "mechanism": "Lactoferrin, as part of flaxseed gum-based coatings, is associated with improved diabetes management via dietary fiber effects.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", 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"G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12124640" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation maintains lactoferrin's functional integrity.", "mechanism": "Lactoferrin/flaxseed gum coatings reduce serum cholesterol, lowering atherosclerosis risk.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12124640" }, { "confidence": "low", "disease": "Gallstone formation", "glycan_involvement": "Glycosylation supports lactoferrin's solubility and function.", "mechanism": "Dietary fiber from flaxseed gum and lactoferrin reduces risk of gallstone formation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12124640" }, { "confidence": "high", "disease": "Microbial contamination/foodborne illness", "glycan_involvement": "Glycosylation enhances lactoferrin's antimicrobial barrier properties.", "mechanism": "Used in nanoemulsion coatings to inhibit bacterial proliferation in spiced beef.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124640" }, { "confidence": "medium", "disease": "Lipid oxidation-related diseases", "glycan_involvement": "Glycosylation stabilizes lactoferrin in emulsions.", "mechanism": "Nanoemulsion coatings with lactoferrin delay lipid oxidation, reducing risk of oxidative stress-related diseases.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124640" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation stabilizes VE-cadherin at the cell surface; altered glycosylation may affect cleavage/endocytosis.", "mechanism": "VE-cadherin cleavage and endocytosis increase vascular permeability and synovial inflammation.", "protein": "VE-cadherin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12124647" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation is essential for ligand binding and function.", "mechanism": "Soluble E-selectin is upregulated in RA serum and synovial fluid, promoting leukocyte adhesion and angiogenesis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation required for ligand recognition.", "mechanism": "P-selectin mediates leukocyte-endothelial interactions; deficiency reduces arthritis severity in mice.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12124647" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "VCAM-1 mediates EPC and leukocyte adhesion to endothelium, promoting angiogenesis and inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation critical for function.", "mechanism": "ICAM-1 upregulation on ECs facilitates leukocyte infiltration into synovium.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Polysialylation modulates adhesion and migration.", "mechanism": "NCAM expression in inflamed vessels indicates incomplete pericyte-EC interaction and vascular instability.", "protein": "NCAM", "relationship_type": "biomarker", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation affects secretion and function.", "mechanism": "vWF expression is increased in RA synovium, correlating with microvascular density and disease activity.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation modulates homophilic binding.", "mechanism": "CD31 is upregulated in RA synovium, marking increased endothelial proliferation and angiogenesis.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Heavily glycosylated; sialylation affects cell adhesion.", "mechanism": "CD34 marks increased microvascular density in RA synovium, correlating with disease severity.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124647" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates receptor binding and stability.", "mechanism": "HB-EGF from macrophages promotes FLS invasiveness and angiogenesis in RA.", "protein": "HB-EGF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12124647" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects trafficking and stability of Cx43 at gap junctions.", "mechanism": "Junctional Cx43 expression in cardiomyocytes is associated with proper electrical coupling; loss or mislocalization is linked to heart failure.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124670" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may affect cTnT stability and detection.", "mechanism": "Elevated cTnT+ cell populations indicate cardiomyocyte presence and are used to assess cardiac injury.", "protein": "Cardiac Troponin T (cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12124670" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation modulates fibronectin's cell adhesion and matrix assembly properties.", "mechanism": "Fibronectin accumulation in ECM contributes to fibrotic scar formation after myocardial infarction.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12124670" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation regulates vitronectin's interaction with integrins and ECM.", "mechanism": "Vitronectin supports cell adhesion and may influence fibrotic remodeling.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "causal", "source_pmcid": "PMC12124670" }, { "confidence": "medium", "disease": "Ventricular remodeling", "glycan_involvement": "Glycosylation is essential for laminin's structural integrity and cell signaling.", "mechanism": "Laminin-111 supports cardiomyocyte differentiation and may aid in tissue repair.", "protein": "Laminin-111", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12124670" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect myosin assembly and function.", "mechanism": "Increased MYH7 expression is associated with mature cardiomyocyte phenotype and contractile function; altered expression is linked to heart failure.", "protein": "Myosin Heavy Chain 7 (MYH7)", "protein_enriched": { "function": "Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamenta", "gene_name": "MYH7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12883" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124670" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation modulates PDGFRA receptor signaling.", "mechanism": "PDGFRA+ progenitors contribute to fibroblast populations in fibrotic tissue.", "protein": "PDGFRA", "relationship_type": "causal", "source_pmcid": "PMC12124670" }, { "confidence": "medium", "disease": "Ventricular remodeling", "glycan_involvement": "Glycosylation affects receptor activation and ligand binding.", "mechanism": "KDR+ progenitors are involved in vascularization and tissue repair after injury.", "protein": "KDR (VEGFR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124670" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect myosin function.", "mechanism": "MYH6 expression is associated with contractile function; altered ratios with MYH7 are linked to disease.", "protein": "Myosin Heavy Chain 6 (MYH6)", "protein_enriched": { "function": "Muscle contraction", "gene_name": "MYH6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124670" }, { "confidence": "low", "disease": "Ventricular remodeling", "glycan_involvement": "Not specified.", "mechanism": "ISL1+ cardiac progenitors are critical for heart development and repair.", "protein": "ISL1", "protein_enriched": { "function": "DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network es", "gene_name": "ISL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61371" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124670" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry into host cells via receptor binding and membrane fusion; main target of neutralizing antibodies.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12124770" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Targeted by neutralizing antibodies and vaccines to prevent infection.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124770" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation required for proper folding and maturation.", "mechanism": "Assists in viral assembly and maturation; modulates E protein conformation.", "protein": "Pre-membrane protein (prM)", "relationship_type": "causal", "source_pmcid": "PMC12124770" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation critical for secretion and immunogenicity.", "mechanism": "Used in diagnostic assays (e.g., LFA) for detection of JEV infection.", "protein": "Non-structural protein 1 (NS1)", "protein_enriched": { "function": "Required in engulfing to control the phagocytosis of apoptotic cell corpses (PubMed:10707082, PubMed:20126385). Required in embryonic development for the correct positioning and orientation of the mit", "gene_name": "ced-10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03206" }, "relationship_type": "biomarker", "source_pmcid": "PMC12124770" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "IgM is a glycoprotein; glycosylation affects detection and function.", "mechanism": "Anti-JEV IgM detected by ELISA is diagnostic for acute infection.", "protein": "Host IgM", "relationship_type": "biomarker", "source_pmcid": "PMC12124770" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation modulates antibody effector functions.", "mechanism": "Neutralizing IgG antibodies confer long-term immunity post-infection or vaccination.", "protein": "Host IgG", "relationship_type": "protective", "source_pmcid": "PMC12124770" }, { "confidence": "medium", "disease": "Dengue virus infection", "glycan_involvement": "Glycosylation influences cross-reactivity and ADE.", "mechanism": "Cross-reactive antibodies to JEV E protein may enhance DENV infection.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "antibody-dependent enhancement", "source_pmcid": "PMC12124770" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "TLR7 is a glycoprotein; glycosylation required for function.", "mechanism": "Recognizes viral RNA, initiates innate immune response.", "protein": "Host TLR7", "relationship_type": "protective", "source_pmcid": "PMC12124770" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation essential for peptide presentation.", "mechanism": "Presents JEV peptides to cytotoxic T cells for immune clearance.", "protein": "Host MHC class I", "relationship_type": "protective", "source_pmcid": "PMC12124770" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation affects secretion and immune recognition.", "mechanism": "Targeted in diagnostic and potential therapeutic strategies.", "protein": "Non-structural protein 1 (NS1)", "protein_enriched": { "function": "Required in engulfing to control the phagocytosis of apoptotic cell corpses (PubMed:10707082, PubMed:20126385). Required in embryonic development for the correct positioning and orientation of the mit", "gene_name": "ced-10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12124770" }, { "confidence": "high", "disease": "Liver Inflammation", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 secretion and stability.", "mechanism": "TNF-\u03b1 release promotes inflammatory response and oxidative stress, worsening liver cell damage.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12124788" }, { "confidence": "high", "disease": "Elevated Liver Enzymes", "glycan_involvement": "Glycosylation affects ALT stability and serum half-life.", "mechanism": "ALT release into serum indicates hepatocyte membrane damage.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12124788" }, { "confidence": "high", "disease": "Elevated Liver Enzymes", "glycan_involvement": "Glycosylation modulates AST activity and clearance.", "mechanism": "AST elevation reflects hepatocyte injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation required for GPx activity.", "mechanism": "GPx reduces oxidative stress by detoxifying peroxides; silymarin increases GPx levels.", "protein": "GPx", "relationship_type": "protective", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation influences SOD folding and activity.", "mechanism": "SOD neutralizes superoxide radicals; silymarin restores SOD levels.", "protein": "SOD", "relationship_type": "protective", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation affects CAT stability.", "mechanism": "CAT decomposes hydrogen peroxide; silymarin increases CAT activity.", "protein": "CAT", "relationship_type": "protective", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Bile Duct Hyperplasia", "glycan_involvement": "Altered glycosylation may affect epithelial integrity.", "mechanism": "Diclofenac induces hyperplasia and vacuolation of bile duct epithelium.", "protein": "Bile Duct Epithelium Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Hepatocyte Necrosis", "glycan_involvement": "Glycosylation maintains membrane protein function.", "mechanism": "Diclofenac damages hepatocyte membranes, leading to necrosis and enzyme leakage.", "protein": "Hepatocyte Membrane Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Elevated Liver Enzymes", "glycan_involvement": "Glycosylation essential for bilirubin transport.", "mechanism": "Impaired carrier glycoproteins lead to increased serum bilirubin.", "protein": "Serum Bilirubin Carrier Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12124788" }, { "confidence": "medium", "disease": "Elevated Liver Enzymes", "glycan_involvement": "Glycosylation modulates ALP activity.", "mechanism": "ALP elevation reflects bile duct injury.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12124788" }, { "confidence": "high", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "THBS4 is an adhesive glycoprotein; glycosylation modulates its ECM binding and signaling.", "mechanism": "THBS4 overexpression in FB3 fibroblasts mediates cell\u2013cell and cell\u2013matrix interactions, promoting pathological fibrosis and cardiac atrophy.", "protein": "THBS4", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12125171" }, { "confidence": "high", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Collagen glycosylation affects fibril assembly and stability.", "mechanism": "Upregulated in FB3 fibroblasts, drives collagen fibril organization and excessive ECM deposition, contributing to fibrosis.", "protein": "COL1A2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "high", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Glycosylation influences collagen cross-linking and tissue stiffness.", "mechanism": "Upregulated in FB3, enhances ECM remodeling and fibrotic scar formation.", "protein": "COL3A1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Glycosylation may regulate SVIL's interaction with actin and ECM.", "mechanism": "SVIL promotes cytoskeletal remodeling and fibroblast migration/proliferation, facilitating fibrosis.", "protein": "SVIL", "protein_enriched": { "function": "Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38", "gene_name": "DUSP10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6W6" }, "relationship_type": "causal", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Glycosylation modulates NTM's adhesive properties.", "mechanism": "NTM upregulation in FB3 marks activated fibroblasts involved in cell adhesion and ECM interactions.", "protein": "NTM", "protein_enriched": { "function": "Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization a", "gene_name": "IBTK", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59324HL", "G80920RR", "G49108TO" ], "uniprot_id": "Q9P2D0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Glycosylation affects NRXN3's synaptic and adhesive functions.", "mechanism": "NRXN3 upregulated in FB3, strengthens cell-cell signaling (NRXN3-NLGN1) with cardiomyocytes.", "protein": "NRXN3", "relationship_type": "biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "APP glycosylation regulates its processing and receptor interactions.", "mechanism": "APP signaling (APP-CD74) from FB3 to macrophages is increased in ICM, modulating immune response.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect secretion and activity.", "mechanism": "PLA2G5 upregulation in FB3 promotes inflammation and ECM remodeling via TGF-\u03b2 and IL-17 pathways.", "protein": "PLA2G5", "relationship_type": "causal", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Glycosylation modulates FN1's matrix assembly and cell adhesion.", "mechanism": "FN1 upregulated in FB3, drives ECM production and fibroblast activation.", "protein": "FN1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "medium", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "Proteoglycan glycosylation critical for ECM binding and TGF-\u03b2 inhibition.", "mechanism": "DCN (decorin) involved in ECM organization; downregulation may impair matrix regulation and promote fibrosis.", "protein": "DCN", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12125171" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "IGFBP-4 is a glycoprotein; glycosylation may affect secretion/stability.", "mechanism": "IGFBP-4 secreted by hPMSCs activates AMPK-FXR pathway, reduces inflammation, and repairs barrier function.", "protein": "IGFBP-4", "protein_enriched": { "function": "IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs w", "gene_name": "IGFBP4", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P22692" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125195" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Glycosylation may modulate IGFBP-4's interaction with receptors.", "mechanism": "Restores tight junctions (\u2191CLDN1, \u2193CLDN2) via AMPK-FXR activation.", "protein": "IGFBP-4", "protein_enriched": { "function": "IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs w", "gene_name": "IGFBP4", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P22692" }, "relationship_type": "protective", "source_pmcid": "PMC12125195" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation status may influence anti-inflammatory activity.", "mechanism": "Suppresses pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6) via AMPK-FXR pathway.", "protein": "IGFBP-4", "protein_enriched": { "function": "IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs w", "gene_name": "IGFBP4", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P22692" }, "relationship_type": "protective", "source_pmcid": "PMC12125195" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may affect detectability in serum.", "mechanism": "Serum IGFBP-4 levels are lower in CD patients than healthy controls.", "protein": "IGFBP-4", "protein_enriched": { "function": "IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs w", "gene_name": "IGFBP4", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P22692" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125195" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "CLDN1 is glycosylated; glycosylation affects tight junction assembly.", "mechanism": "Decreased CLDN1 expression leads to impaired barrier; restored by hPMSCs/IGFBP-4.", "protein": "Claudin-1 (CLDN1)", "relationship_type": "causal", "source_pmcid": "PMC12125195" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "CLDN2 glycosylation may regulate paracellular permeability.", "mechanism": "Increased CLDN2 disrupts barrier; reduced by hPMSCs/IGFBP-4.", "protein": "Claudin-2 (CLDN2)", "relationship_type": "causal", "source_pmcid": "PMC12125195" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "FXR is glycosylated; glycosylation may affect nuclear localization.", "mechanism": "FXR activation (via AMPK, IGFBP-4) reduces inflammation and restores barrier.", "protein": "FXR (NR1H4)", "relationship_type": "protective", "source_pmcid": "PMC12125195" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "S100A8 is a glycoprotein; glycosylation may affect immune recognition.", "mechanism": "Elevated S100A8 indicates inflammation; reduced by hPMSC therapy.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12125195" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "S100A9 glycosylation may modulate inflammatory signaling.", "mechanism": "Elevated S100A9 indicates inflammation; reduced by hPMSC therapy.", "protein": "S100A9", "relationship_type": "biomarker", "source_pmcid": "PMC12125195" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may affect IGFBP-3 function, but not relevant in this context.", "mechanism": "IGFBP-3 is highly secreted by hPMSCs but does not activate AMPK-FXR or confer therapeutic effect in CD.", "protein": "IGFBP-3", "relationship_type": "neutral", "source_pmcid": "PMC12125195" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "CD9 is a glycoprotein; glycosylation may affect its membrane localization and function.", "mechanism": "CD9 expression is significantly decreased in sarcopenia; involved in ATP biosynthesis, mitochondrial biogenesis, and oxidative phosphorylation.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation may influence drug binding and CD9 stability.", "mechanism": "Targeting CD9 with drugs (dapoxetine, levomilnacipran, milnacipran) may modulate sarcopenia progression.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Potential role of glycosylation in CD9-mediated signaling.", "mechanism": "CD9 is enriched in pathways associated with ALS.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Glycosylation may affect CD9's role in cardiac tissue.", "mechanism": "CD9 participates in pathways linked to diabetic cardiomyopathy.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Huntington disease", "glycan_involvement": "Glycosylation may modulate CD9's neurobiological functions.", "mechanism": "CD9 is involved in Huntington disease-related pathways.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation may regulate CD9-mediated cell interactions.", "mechanism": "CD9 implicated in cardiac hypertrophy via cell signaling.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "causal", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Glycosylation may affect CD9's immune signaling.", "mechanism": "CD9 modulates inflammatory responses.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "causal", "source_pmcid": "PMC12125282" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation influences CD9's role in tumor progression.", "mechanism": "CD9 involved in cancer cell migration, proliferation, and differentiation.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "causal", "source_pmcid": "PMC12125282" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Apoa1 glycosylation affects lipid transport and muscle health.", "mechanism": "Apoa1 expression altered in sarcopenia; involved in lipid metabolism.", "protein": "Apoa1", "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation may regulate Cd81's membrane function.", "mechanism": "Cd81 identified as a key gene in sarcopenia; tetraspanin family member.", "protein": "Cd81", "relationship_type": "biomarker", "source_pmcid": "PMC12125282" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "GGT is a glycoprotein; altered glycosylation may affect its stability and serum levels.", "mechanism": "Elevated GGT is associated with increased risk of T2DM, possibly reflecting liver dysfunction and oxidative stress.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates function and clearance.", "mechanism": "Low HDL-C is a strong predictor of T2DM; HDL particles contain glycoproteins involved in lipid metabolism.", "protein": "High-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "AST is a glycoprotein; glycosylation may influence serum levels.", "mechanism": "Elevated AST is associated with increased T2DM risk, reflecting liver injury.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect secretion and activity.", "mechanism": "Elevated ALT is associated with increased T2DM risk, reflecting hepatic steatosis.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "ALP is highly glycosylated; glycan structures affect its serum half-life.", "mechanism": "Elevated ALP is associated with increased T2DM risk, possibly via liver or bone metabolism.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Altered glycosylation may reflect liver pathology.", "mechanism": "Elevated GGT may indicate NAFLD, which is strongly linked to T2DM.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12125507" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects sCD14 stability and immune signaling.", "mechanism": "Soluble CD14 (sCD14) is elevated in HIV and drives endothelial activation and plaque formation.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates ICAM-1 cell surface expression and function.", "mechanism": "sICAM-1 promotes immune cell adhesion and accumulation in vessel walls, contributing to plaque development.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for VCAM-1 adhesion properties.", "mechanism": "sVCAM-1 facilitates leukocyte recruitment to endothelium, promoting atherogenesis.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation critical for LDLR folding and cell surface trafficking.", "mechanism": "Statins upregulate LDLR, increasing LDL clearance and reducing dyslipidemia risk.", "protein": "LDL receptor (LDLR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates CRP solubility and immune recognition.", "mechanism": "Elevated CRP reflects systemic inflammation and predicts CVD risk in HIV.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "N-glycosylation influences IL-6 secretion and receptor binding.", "mechanism": "IL-6 is elevated in HIV and CVD, mediating chronic inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12125728" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation affects CD40-L stability and receptor interaction.", "mechanism": "CD40-L promotes platelet aggregation and vascular inflammation, increasing CAD risk.", "protein": "CD40 ligand (CD40-L)", "relationship_type": "causal", "source_pmcid": "PMC12125728" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates PLA2G7 activity and plasma half-life.", "mechanism": "PLA2G7 is a marker of arterial inflammation and plaque instability.", "protein": "PLA2G7", "relationship_type": "biomarker", "source_pmcid": "PMC12125728" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for PCOLCE secretion and ECM function.", "mechanism": "Statins increase PCOLCE, enhancing collagen maturation and plaque stability.", "protein": "PCOLCE", "relationship_type": "protective", "source_pmcid": "PMC12125728" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates JAM-A adhesive properties.", "mechanism": "JAM-A regulates endothelial permeability and leukocyte extravasation, influencing vascular inflammation.", "protein": "JAM-A", "relationship_type": "biomarker", "source_pmcid": "PMC12125728" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "PHB1 is a glycoprotein; glycosylation may affect stability and degradation.", "mechanism": "PHB1 degradation leads to mitochondrial fragmentation and dysfunction in cardiomyocytes, contributing to heart failure.", "protein": "Prohibitin 1 (PHB1)", "protein_enriched": { "function": "Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing path", "gene_name": "PFDN5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99471" }, "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "PHB2 is a glycoprotein; glycosylation may regulate mitochondrial localization.", "mechanism": "PHB2 depletion disrupts mitochondrial function, increases ROS, and promotes hypertrophy.", "protein": "Prohibitin 2 (PHB2)", "protein_enriched": { "function": "Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and tran", "gene_name": "PHB2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G96091TT", "G49108TO" ], "uniprot_id": "Q99623" }, "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Potential glycoprotein; glycosylation status not specified.", "mechanism": "Reduced OPA-1 levels cause mitochondrial fragmentation and impaired energetics in failing hearts.", "protein": "OPA-1", "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "high", "disease": "Autosomal dominant optic atrophy", "glycan_involvement": "Not specified.", "mechanism": "OPA-1 mutations cause mitochondrial dysfunction leading to optic atrophy.", "protein": "OPA-1", "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "PHB1 glycosylation may affect mitochondrial stability.", "mechanism": "PHB1 knockdown increases ROS and reduces ATP, promoting hypertrophy.", "protein": "Prohibitin 1 (PHB1)", "protein_enriched": { "function": "Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing path", "gene_name": "PFDN5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99471" }, "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Genetic deletion of mTOR in heart leads to dilated heart failure.", "protein": "mTOR", "protein_enriched": { "function": "Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098,", "gene_name": "MTOR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G60667HJ", "G41247ZX", "G49108TO" ], "uniprot_id": "P42345" }, "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Not a glycoprotein.", "mechanism": "AMPK activation protects against heart failure via autophagy and reduced oxidative stress.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12125784" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Not a glycoprotein.", "mechanism": "AMPK activation induces apoptosis and suppresses tumor growth.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125784" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "PHB1 glycosylation may regulate stability.", "mechanism": "PHB1 levels decrease during cellular senescence, contributing to mitochondrial dysfunction in neurodegeneration.", "protein": "Prohibitin 1 (PHB1)", "protein_enriched": { "function": "Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing path", "gene_name": "PFDN5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99471" }, "relationship_type": "causal", "source_pmcid": "PMC12125784" }, { "confidence": "medium", "disease": "Renal disease", "glycan_involvement": "PHB1 glycosylation may affect mitochondrial localization.", "mechanism": "PHB1 maintains mitochondrial function, reducing oxidative stress and inflammation in kidney cells.", "protein": "Prohibitin 1 (PHB1)", "protein_enriched": { "function": "Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing path", "gene_name": "PFDN5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99471" }, "relationship_type": "protective", "source_pmcid": "PMC12125784" }, { "confidence": "high", "disease": "Adrenal insufficiency", "glycan_involvement": "CBG is a glycoprotein; glycosylation affects its stability and cortisol binding.", "mechanism": "CBG binds ~80-90% of plasma cortisol, affecting total cortisol measurement and bioavailability; lower CBG may contribute to lower total cortisol in boys, impacting diagnosis.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "medium", "disease": "Short stature", "glycan_involvement": "Glycosylation modulates CBG function and half-life.", "mechanism": "Altered CBG levels may influence cortisol bioavailability, potentially affecting growth and HPA axis assessment in children with short stature.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "high", "disease": "Growth hormone deficiency (GHD)", "glycan_involvement": "GH is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "GH levels measured during GST are used to diagnose GHD in children with short stature.", "protein": "Growth hormone (GH)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "medium", "disease": "Growth hormone deficiency (GHD)", "glycan_involvement": "IGF-1 is glycosylated, influencing stability and receptor binding.", "mechanism": "IGF-1 levels reflect GH activity and are used to support GHD diagnosis.", "protein": "Insulin-like growth factor 1 (IGF-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "low", "disease": "Pituitary abnormality", "glycan_involvement": "Glycosylation regulates CBG function.", "mechanism": "CBG levels may be altered in pituitary disorders, affecting cortisol transport and measurement.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "medium", "disease": "Adrenal insufficiency", "glycan_involvement": "Altered glycosylation can affect CBG levels and function.", "mechanism": "Low CBG may lead to lower total cortisol, potentially resulting in misdiagnosis of adrenal insufficiency.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "causal", "source_pmcid": "PMC12125804" }, { "confidence": "medium", "disease": "Adrenal insufficiency", "glycan_involvement": "Estrogen-induced glycosylation increases CBG levels.", "mechanism": "Higher CBG (e.g., in girls or with estrogen exposure) increases total cortisol, potentially protecting against underdiagnosis.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "protective", "source_pmcid": "PMC12125804" }, { "confidence": "high", "disease": "Short stature", "glycan_involvement": "GH glycosylation affects its bioactivity.", "mechanism": "GH stimulation test is used to assess GH axis in children with short stature.", "protein": "Growth hormone (GH)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "high", "disease": "Sex differences in HPA axis function", "glycan_involvement": "Sex hormones modulate CBG glycosylation and levels.", "mechanism": "CBG levels are higher in girls, contributing to higher total cortisol and sex differences in HPA axis assessment.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "medium", "disease": "Age-related changes in HPA axis", "glycan_involvement": "Age-dependent glycosylation changes may affect CBG levels.", "mechanism": "CBG levels decrease with age, contributing to lower total cortisol in older children.", "protein": "Corticosteroid-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12125804" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Tenascin-C is a glycoprotein; glycosylation is essential for its ECM localization and function.", "mechanism": "Upregulation of Tenascin-C in diabetic heart promotes cardiac contractile dysfunction, fibrosis, inflammation, and metabolic disturbances.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects Tenascin-C stability and secretion.", "mechanism": "Elevated plasma Tenascin-C levels in heart failure patients, regardless of diabetes status.", "protein": "Tenascin-C", "relationship_type": "biomarker", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation modulates Tenascin-C interactions with ECM and cells.", "mechanism": "Tenascin-C promotes fibroblast-to-myofibroblast transition and collagen deposition in diabetic hearts.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation may influence Tenascin-C binding to endothelial receptors.", "mechanism": "Tenascin-C upregulation impairs endothelium-dependent vasorelaxation in diabetes.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation may affect Tenascin-C's immunomodulatory properties.", "mechanism": "Recombinant Tenascin-C induces pro-inflammatory cytokines (IL-6, TNF-\u03b1) and oxidative stress markers (NOX4) in cardiomyocytes.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "medium", "disease": "Metabolic disturbance", "glycan_involvement": "Glycosylation may regulate Tenascin-C's interaction with metabolic pathways.", "mechanism": "Tenascin-C upregulation in diabetes is associated with altered metabolic gene expression (e.g., Ppara, Fabp4).", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Targeting glycosylated Tenascin-C may modulate its pathogenic effects.", "mechanism": "TNC knockout mice are protected from cardiac dysfunction, fibrosis, and endothelial impairment in diabetes.", "protein": "Tenascin-C", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Cardiac fibrosis", "glycan_involvement": "Loss of glycosylated Tenascin-C reduces ECM remodeling.", "mechanism": "TNC deficiency reduces cardiac fibrosis in diabetic mice.", "protein": "Tenascin-C", "relationship_type": "protective", "source_pmcid": "PMC12125828" }, { "confidence": "medium", "disease": "Apoptosis (cardiac tissue)", "glycan_involvement": "Glycosylation may affect Tenascin-C's apoptotic signaling.", "mechanism": "Diabetes-induced Tenascin-C upregulation increases cardiac apoptosis; TNC deficiency mitigates this effect.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Glycosylation is required for Tenascin-C secretion and detection in plasma.", "mechanism": "High glucose induces Tenascin-C expression in human cardiac fibroblasts and mouse cardiomyocytes; plasma TNC is elevated in DCM.", "protein": "Tenascin-C", "relationship_type": "biomarker", "source_pmcid": "PMC12125828" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "HMGA1 is a glycoprotein; glycosylation may affect its chromatin binding and transcriptional activity.", "mechanism": "Upregulated HMGA1 promotes cardiomyocyte injury via the miR-296-5p/HMGA1 axis.", "protein": "HMGA1", "relationship_type": "causal", "source_pmcid": "PMC12125867" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may modulate HMGA1's function in metabolic regulation.", "mechanism": "HMGA1 is implicated in diabetes and its cardiovascular sequelae.", "protein": "HMGA1", "relationship_type": "causal", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Bax glycosylation may influence its apoptotic activity.", "mechanism": "High glucose upregulates Bax, promoting cardiomyocyte apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation may stabilize Bcl-2 and enhance anti-apoptotic function.", "mechanism": "Bcl-2 downregulation under high glucose increases apoptosis; FENDRR knockdown restores Bcl-2.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "LDH glycosylation affects stability and serum levels.", "mechanism": "Elevated LDH indicates cardiomyocyte injury in DCM.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation modulates CK-MB release and detection.", "mechanism": "Increased CK-MB reflects myocardial damage in DCM.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "AST glycosylation influences enzyme activity and serum levels.", "mechanism": "Elevated AST is a marker of cardiomyocyte injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12125867" }, { "confidence": "medium", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation may affect SOD stability and antioxidant function.", "mechanism": "Reduced SOD activity under high glucose exacerbates oxidative stress in DCM.", "protein": "SOD", "relationship_type": "protective", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Diabetic cardiomyopathy (DCM)", "glycan_involvement": "TNF-\u03b1 glycosylation is critical for secretion and receptor binding.", "mechanism": "Upregulated TNF-\u03b1 drives inflammation in DCM; FENDRR knockdown reduces TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12125867" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation may regulate HMGA1's nuclear localization and activity.", "mechanism": "HMGA1 upregulation is implicated in cardiac hypertrophy and myocarditis.", "protein": "HMGA1", "relationship_type": "causal", "source_pmcid": "PMC12125867" }, { "confidence": "high", "disease": "Liver Ischemia-Reperfusion Injury", "glycan_involvement": "Glycogen breakdown reflects glycan metabolism changes.", "mechanism": "Altered glycogen levels detected by SERS indicate metabolic disruption during IR injury.", "protein": "Glycogen", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Liver Transplant Dysfunction", "glycan_involvement": "Altered glycosylation may affect albumin stability and detection.", "mechanism": "Serum protein changes (including albumin) reflect liver synthetic function loss post-IR injury.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Collagen glycosylation modulates extracellular matrix deposition.", "mechanism": "Increased collagen signals (Amide I/III) indicate fibrotic progression after IR injury.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Liver Inflammation", "glycan_involvement": "Tyrosine O-glycosylation may influence inflammatory signaling.", "mechanism": "Elevated tyrosine-related Raman peaks correlate with inflammatory zones in liver tissue.", "protein": "Tyrosine-rich proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Hepatocyte Necrosis", "glycan_involvement": "Phenylalanine glycosylation status may change during cell death.", "mechanism": "Variations in phenylalanine peaks (1000 cm\u207b\u00b9) associate with necrotic changes in hepatocytes.", "protein": "Phenylalanine-rich proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Liver Ischemia-Reperfusion Injury", "glycan_involvement": "Tryptophan glycosylation may be altered under stress.", "mechanism": "Tryptophan peak changes reflect oxidative stress and protein damage in IR injury.", "protein": "Tryptophan-rich proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Immune Rejection", "glycan_involvement": "N-glycosylation with mannose is key in immune recognition.", "mechanism": "D-mannose peaks may indicate immune activation and glycoprotein turnover during rejection.", "protein": "D-mannose containing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Metabolic Dysfunction", "glycan_involvement": "Altered glycosylation impacts protein function and metabolism.", "mechanism": "Glucose-related peaks signal metabolic derangement in liver injury.", "protein": "Glucose-modified proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects protein folding and matrix deposition.", "mechanism": "Amide peaks reflect protein backbone changes during fibrotic remodeling.", "protein": "Amide III/Amide I proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "medium", "disease": "Liver Ischemia-Reperfusion Injury", "glycan_involvement": "Glycosylation can modulate disulfide bond formation.", "mechanism": "Disulfide stretch signals indicate oxidative stress and protein structural changes.", "protein": "Disulfide bond-containing proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126103" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Secreted glycoprotein; glycosylation required for stability and secretion.", "mechanism": "Promotes cardiac angiogenesis, reduces infarct size, improves cardiac function via DIP2A, TGF\u03b2-Smad2/3, AMPK, Akt/mTOR, and Erk1/2 pathways.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12126109" }, { "confidence": "high", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation facilitates extracellular activity.", "mechanism": "Upregulated in ischemia; acts as a biomarker and promotes angiogenesis for tissue repair.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12126109" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Elevated FSTL1 correlates with improved hemodynamics and survival; promotes angiogenesis and reduces remodeling.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12126109" }, { "confidence": "medium", "disease": "Diabetes mellitus (cardiac complications)", "glycan_involvement": "Glycosylation supports stability and activity.", "mechanism": "Exercise and insulin increase FSTL1, improving cardiac vascularization and function.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12126109" }, { "confidence": "high", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation essential for cardiokine activity.", "mechanism": "FSTL1 deficiency leads to hypertrophy and dysfunction; normal FSTL1 prevents pathological remodeling.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "protective/causal", "source_pmcid": "PMC12126109" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for anti-inflammatory effects.", "mechanism": "Promotes angiogenesis and vascular repair, reduces inflammation.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "protective", "source_pmcid": "PMC12126109" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation affects extracellular signaling.", "mechanism": "Regulates fibroblast proliferation; overexpression may cause fibrosis, balanced expression prevents it.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12126109" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation required for receptor binding.", "mechanism": "Induced by FSTL1; promotes endothelial proliferation and angiogenesis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126109" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation enables secretion into bloodstream.", "mechanism": "Circulating FSTL1 levels increase post-infarction, indicating severity and tissue damage.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "biomarker", "source_pmcid": "PMC12126109" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation required for cardioprotective function.", "mechanism": "Higher myocardial FSTL1 expression associated with better survival; regulates angiogenesis and remodeling.", "protein": "Follistatin-like 1 (FSTL1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126109" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Indirect\u2014regulates glycoprotein (ECM) gene expression via m6A RNA methylation.", "mechanism": "Regulates m6A modification affecting inflammatory response, ECM degradation, and chondrocyte apoptosis.", "protein": "METTL3", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, di", "gene_name": "METTL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U44" }, "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Indirect\u2014modulates m6A on transcripts encoding glycoproteins.", "mechanism": "Upregulation activates Wnt/\u03b2-catenin signaling, increasing inflammation and ECM degradation.", "protein": "WTAP", "protein_enriched": { "function": "Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (P", "gene_name": "WTAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15007" }, "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Indirect\u2014demethylates m6A on ECM glycoprotein mRNAs.", "mechanism": "Downregulation promotes ECM degradation and chondrocyte apoptosis; overexpression is protective.", "protein": "FTO", "protein_enriched": { "function": "RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:220027", "gene_name": "FTO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9C0B1" }, "relationship_type": "protective", "source_pmcid": "PMC12126110" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Indirect\u2014affects m6A on glycoprotein-related RNAs.", "mechanism": "Upregulation induces inflammation via NF-\u03baB; downregulation promotes ECM degradation.", "protein": "ALKBH5", "protein_enriched": { "function": "Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubM", "gene_name": "ALKBH5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6P6C2" }, "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "medium", "disease": "OA immune infiltration", "glycan_involvement": "Indirect\u2014regulates stability of mRNAs encoding glycoproteins.", "mechanism": "Downregulation correlates with altered immune cell infiltration in OA synovium.", "protein": "YTHDF2", "protein_enriched": { "function": "Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification pr", "gene_name": "YTHDF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5A9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126110" }, { "confidence": "medium", "disease": "Chondrocyte ferroptosis", "glycan_involvement": "Direct\u2014MMP3 is a glycoprotein, its expression is regulated.", "mechanism": "Upregulation stabilizes MMP3 mRNA, promoting ferroptosis in chondrocytes.", "protein": "IGF2BP1", "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "medium", "disease": "Osteogenic differentiation defect", "glycan_involvement": "Indirect\u2014regulates m6A on osteogenic glycoprotein mRNAs.", "mechanism": "Downregulation impairs osteogenic differentiation; overexpression restores differentiation.", "protein": "HNRNPA2B1", "protein_enriched": { "function": "Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-", "gene_name": "HNRNPA2B1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P22626" }, "relationship_type": "protective", "source_pmcid": "PMC12126110" }, { "confidence": "medium", "disease": "Cartilage ECM degradation", "glycan_involvement": "Indirect\u2014regulates m6A on ECM glycoprotein mRNAs.", "mechanism": "Upregulation increases ADAM8 expression, promoting ECM degradation.", "protein": "METTL14", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryoni", "gene_name": "METTL14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HCE5" }, "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "high", "disease": "Cartilage ECM degradation", "glycan_involvement": "Direct\u2014MMP3 is a glycoprotein involved in ECM breakdown.", "mechanism": "Upregulated by IGF2BP1, directly degrades ECM glycoproteins.", "protein": "MMP3", "protein_enriched": { "function": "Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activa", "gene_name": "MMP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P08254" }, "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "high", "disease": "Cartilage ECM degradation", "glycan_involvement": "Direct\u2014structural glycoproteins degraded in OA.", "mechanism": "Degradation is a hallmark of OA, regulated by m6A-modified gene expression.", "protein": "ECM glycoproteins (e.g., aggrecan, collagen II)", "relationship_type": "causal", "source_pmcid": "PMC12126110" }, { "confidence": "high", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation modulates receptor function and immune signaling.", "mechanism": "Upregulated in inflamed pulp; regulates immune cell activation and signaling.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "high", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation critical for ligand binding and cell-cell interactions.", "mechanism": "Upregulated in inflamed tissue; mediates leukocyte adhesion and transmigration.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "Heavily glycosylated; glycan structures regulate hyaluronan binding and migration.", "mechanism": "Upregulated in inflammation; involved in cell adhesion and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation affects integrin activation and ligand binding.", "mechanism": "Increased expression in monocytes during inflammation; mediates immune cell adhesion.", "protein": "ITGAM (CD11b)", "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation influences receptor stability and immune interactions.", "mechanism": "Expressed by macrophages/B cells; upregulated in inflamed pulp, co-stimulatory for T cell activation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "high", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation modulates secretion and enzymatic activity.", "mechanism": "Upregulated in inflamed pulp; degrades extracellular matrix, promotes leukocyte migration.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation required for receptor trafficking and ligand binding.", "mechanism": "Upregulated; mediates chemotaxis of immune cells to inflamed pulp.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation modulates receptor function and cell migration.", "mechanism": "Upregulated; directs migration of immune cells in inflammation.", "protein": "CCR7", "protein_enriched": { "function": "Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions", "gene_name": "CCR7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P32248" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "N-glycosylation required for proper folding and cell surface expression.", "mechanism": "Upregulated in response to bacterial infection; initiates inflammatory signaling.", "protein": "TLR2", "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "medium", "disease": "Pulpitis", "glycan_involvement": "O-glycosylation may affect secretion and chemokine activity.", "mechanism": "Produced in response to pro-inflammatory cytokines; recruits monocytes to inflamed pulp.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126159" }, { "confidence": "high", "disease": "Rheumatic heart disease (RHD)", "glycan_involvement": "ACE is a glycoprotein; glycosylation is essential for its enzymatic activity and cell surface localization.", "mechanism": "ACE promotes conversion of Ang I to Ang II, which enhances TGF-\u03b21 signaling, leading to myofibroblast differentiation and fibrosis in heart valves.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Rheumatic heart disease (RHD)", "glycan_involvement": "TGF-\u03b21 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "TGF-\u03b21 is released during inflammation, activates SMAD/MAPK/ERK pathways, induces myofibroblast differentiation and extracellular matrix synthesis, driving valve fibrosis.", "protein": "Transforming growth factor-beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation required for ACE function.", "mechanism": "ACE activity increases Ang II, which stimulates TGF-\u03b21 signaling and fibrotic tissue formation.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "causal", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 stability and activity.", "mechanism": "TGF-\u03b21 directly induces fibroblast-to-myofibroblast differentiation and collagen production.", "protein": "Transforming growth factor-beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC12126187" }, { "confidence": "medium", "disease": "Acute rheumatic fever", "glycan_involvement": "Glycosylation status may affect ACE detection and activity.", "mechanism": "ACE levels increase in response to TGF-\u03b21-induced inflammation, marking progression toward RHD.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "biomarker", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Rheumatic heart disease (RHD)", "glycan_involvement": "Not glycosylated; used as a marker.", "mechanism": "\u03b1SMA expression marks myofibroblast differentiation and fibrosis in valve tissue.", "protein": "Alpha-smooth muscle actin (\u03b1SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Rheumatic heart disease (RHD)", "glycan_involvement": "Glycosylation necessary for ACE inhibitor binding and function.", "mechanism": "ACE inhibition by Lisinopril suppresses TGF-\u03b21/SMAD/TAK1 pathways, reducing fibrosis and myofibroblast differentiation.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Rheumatic heart disease (RHD)", "glycan_involvement": "Glycosylation affects TGF-\u03b21 secretion and receptor interaction.", "mechanism": "Targeting TGF-\u03b21 signaling can prevent myofibroblast differentiation and valve fibrosis.", "protein": "Transforming growth factor-beta 1 (TGF-\u03b21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation required for ACE inhibitor efficacy.", "mechanism": "ACE inhibition (e.g., Lisinopril) reduces Ang II and downstream TGF-\u03b21 signaling, attenuating fibrotic changes.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "protective", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 bioactivity.", "mechanism": "Inhibition of TGF-\u03b21 signaling reduces fibroblast activation and collagen deposition.", "protein": "Transforming growth factor-beta 1 (TGF-\u03b21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126187" }, { "confidence": "high", "disease": "Protein-losing enteropathy", "glycan_involvement": "Glycosylation affects albumin stability and half-life.", "mechanism": "Low serum albumin indicates protein loss via the gut after Fontan surgery.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "high", "disease": "Protein-losing enteropathy", "glycan_involvement": "Glycoprotein content in serum is altered in disease.", "mechanism": "Reduced total serum protein reflects enteric protein loss post-Fontan.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "medium", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation modulates BNP secretion and clearance.", "mechanism": "BNP levels predict morbidity and mortality after Fontan surgery.", "protein": "Brain-type Natriuretic Peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "medium", "disease": "Fontan-associated liver disease", "glycan_involvement": "Altered glycosylation in liver disease affects albumin function.", "mechanism": "Low albumin signals impaired liver synthetic function post-Fontan.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "medium", "disease": "Fontan-associated liver disease", "glycan_involvement": "Glycosylation may affect AST stability and detection.", "mechanism": "Elevated AST indicates liver injury after Fontan surgery.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "medium", "disease": "Fontan-associated liver disease", "glycan_involvement": "Glycosylation can influence ALT activity and serum levels.", "mechanism": "ALT elevation reflects hepatocellular damage in Fontan patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "low", "disease": "Thromboembolism", "glycan_involvement": "Glycosylation affects albumin's anticoagulant properties.", "mechanism": "Normal albumin levels may protect against hypercoagulability post-Fontan.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12126189" }, { "confidence": "low", "disease": "Cyanosis", "glycan_involvement": "Glycosylation status may change in hypoxic conditions.", "mechanism": "Low albumin may be associated with chronic hypoxemia and cyanosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "low", "disease": "Thromboembolism", "glycan_involvement": "Glycosylation affects BNP clearance and activity.", "mechanism": "Elevated BNP may indicate increased risk of thromboembolic events post-Fontan.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "medium", "disease": "Fontan-associated liver disease", "glycan_involvement": "Glycoprotein synthesis is altered in liver disease.", "mechanism": "Low total protein reflects impaired hepatic synthesis in Fontan patients.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12126189" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Factor V is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Factor V Leiden mutation impairs inactivation by Protein C, increasing clot formation.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "Glycosylation may modulate Factor V activity and clearance.", "mechanism": "Mutant Factor V increases risk of venous clots due to resistance to Protein C.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "medium", "disease": "Arterial Thrombosis", "glycan_involvement": "Glycosylation influences Factor V's interaction with other coagulation proteins.", "mechanism": "Factor V Leiden mutation predisposes to arterial clot formation.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Protein C glycosylation is essential for secretion and anticoagulant activity.", "mechanism": "Protein C inactivates Factor V; mutation reduces this effect, increasing thrombosis risk.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for antithrombin III stability and activity.", "mechanism": "Antithrombin III inhibits thrombin and other clotting factors, reducing thrombosis risk.", "protein": "Antithrombin III", "relationship_type": "protective", "source_pmcid": "PMC12126192" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects Protein S secretion and function.", "mechanism": "Protein S acts as a cofactor for Protein C; deficiency increases thrombosis risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12126192" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates immunogenicity and function.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are markers for antiphospholipid syndrome, increasing thrombosis risk.", "protein": "Beta-2 Glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation may affect Factor V's plasma half-life and activity.", "mechanism": "Factor V Leiden mutation is the most common inherited cause of thrombophilia.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Deep Vein Thrombosis", "glycan_involvement": "Glycosylation impacts Factor V's interaction with other coagulation factors.", "mechanism": "Factor V Leiden mutation increases risk of DVT due to impaired regulation by Protein C.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "medium", "disease": "Pulmonary Embolism", "glycan_involvement": "Glycosylation may influence Factor V's function in coagulation cascade.", "mechanism": "Factor V Leiden mutation increases risk of pulmonary embolism via enhanced clot formation.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12126192" }, { "confidence": "high", "disease": "Hypogammaglobulinemia", "glycan_involvement": "IgA glycosylation affects stability and immune function.", "mechanism": "Low serum IgA levels indicate immunodeficiency post-transplant.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "high", "disease": "Hypogammaglobulinemia", "glycan_involvement": "IgM glycosylation is critical for pentamer formation and function.", "mechanism": "Low IgM levels reflect impaired humoral immunity after HSCT.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "high", "disease": "Graft Versus Host Disease (GVHD)", "glycan_involvement": "HLA glycosylation modulates antigen presentation and immune recognition.", "mechanism": "HLA mismatch between donor and recipient triggers GVHD.", "protein": "Human Leukocyte Antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "CD34 is heavily glycosylated, affecting cell adhesion and migration.", "mechanism": "CD34+ cells are used in immunostaining to identify dysplastic hematopoietic cells.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Graft Versus Host Disease (GVHD)", "glycan_involvement": "CD20 glycosylation may influence antibody binding and efficacy.", "mechanism": "Rituximab (anti-CD20) used for GVHD prophylaxis.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Graft Versus Host Disease (GVHD)", "glycan_involvement": "CD3 glycosylation affects T-cell receptor function.", "mechanism": "CD3-depleted grafts reduce T-cell mediated GVHD.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "Glycosylation regulates c-Kit receptor signaling.", "mechanism": "CD117+ cells indicate abnormal myeloid differentiation.", "protein": "CD117 (c-Kit)", "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Integrin glycosylation modulates platelet function.", "mechanism": "CD61 immunostaining identifies megakaryocyte dysplasia in MDS.", "protein": "CD61 (Integrin beta-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Chronic Colitis", "glycan_involvement": "CD68 glycosylation affects macrophage activation.", "mechanism": "CD68+ macrophages indicate inflammation in gut biopsies.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "MPO glycosylation influences enzyme stability and activity.", "mechanism": "MPO immunostaining marks myeloid lineage in skin and marrow biopsies.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126211" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Aberrant glycosylation promotes tumor cell adhesion and immune evasion.", "mechanism": "Glycoproteins on melanoma cells mediate metastasis, including to cardiac tissue.", "protein": "Melanoma-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12126262" }, { "confidence": "medium", "disease": "Undifferentiated malignant spindle cell neoplasm", "glycan_involvement": "Altered glycosylation enhances invasiveness.", "mechanism": "Tumor glycoproteins facilitate metastatic spread to the heart.", "protein": "Spindle cell neoplasm glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12126262" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects BNP stability and secretion.", "mechanism": "Elevated BNP indicates cardiac dysfunction due to tumor burden.", "protein": "Brain natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12126262" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Glycosylation required for erythropoietin activity.", "mechanism": "Used to treat anemia in cancer patients.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126262" }, { "confidence": "medium", "disease": "Cardiac metastasis", "glycan_involvement": "Glycosylation influences troponin clearance.", "mechanism": "Elevated troponin reflects myocardial injury from tumor infiltration.", "protein": "High-sensitivity troponin", "relationship_type": "biomarker", "source_pmcid": "PMC12126262" }, { "confidence": "medium", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Elevated levels indicate liver and bone involvement.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126262" }, { "confidence": "medium", "disease": "Immune-related hepatitis", "glycan_involvement": "Fc glycosylation regulates effector function.", "mechanism": "IgG-mediated immune response contributes to immunotherapy toxicity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12126262" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "N-glycosylation modulates PD-1 cell surface expression.", "mechanism": "Targeted by nivolumab to enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126262" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation affects CTLA-4 trafficking and function.", "mechanism": "Targeted by ipilimumab to block immune inhibition.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126262" }, { "confidence": "medium", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation influences albumin half-life.", "mechanism": "Low albumin reflects poor nutritional status and advanced disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126262" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "CD36 is a glycoprotein; glycosylation may affect its cell surface expression and immune interactions.", "mechanism": "Loss-of-function missense variant (rs75326924) in CD36 reduces asthma risk; associated with decreased immune protein expression and altered lymphocyte/ILC2 function.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "protective", "source_pmcid": "PMC12126482" }, { "confidence": "high", "disease": "Platelet glycoprotein IV deficiency", "glycan_involvement": "Glycosylation critical for CD36 stability and function on platelets.", "mechanism": "rs75326924 variant causes CD36 deficiency, leading to platelet glycoprotein IV deficiency.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "IL-7 is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Downregulated in carriers of CD36 rs75326924; IL-7 modulates T/B cell activation in asthma.", "protein": "Interleukin-7", "protein_enriched": { "function": "Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintain", "gene_name": "IL7", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P13232" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates OSM stability and activity.", "mechanism": "Downregulated in CD36 variant carriers; OSM influences immune cell activation and cytokine production in asthma.", "protein": "Oncostatin M", "relationship_type": "biomarker", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "N-glycosylation regulates VEGFA secretion and receptor interaction.", "mechanism": "Downregulated in CD36 variant carriers; VEGFA involved in airway remodeling and inflammation.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126482" }, { "confidence": "high", "disease": "Eosinophilic asthma", "glycan_involvement": "TSLP is a glycoprotein; glycosylation required for secretion.", "mechanism": "TSLP locus associated with eosinophilic asthma; TSLP promotes Th2 inflammation.", "protein": "TSLP", "protein_enriched": { "function": "Cytokine that induces the release of T-cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly a", "gene_name": "TSLP", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q969D9" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Eosinophilic asthma", "glycan_involvement": "Predicted glycoprotein; glycosylation may affect function.", "mechanism": "GSDMB locus associated with eosinophilic asthma; involved in epithelial cell death and inflammation.", "protein": "GSDMB", "protein_enriched": { "function": "Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851). This form constitutes the precursor of the pore-forming protein: upon cleavage", "gene_name": "GSDMB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8TAX9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Eosinophilic asthma", "glycan_involvement": "Glycoprotein status; glycosylation may modulate activity.", "mechanism": "PPP1R11 locus associated with eosinophilic asthma; regulatory role in immune signaling.", "protein": "PPP1R11", "protein_enriched": { "function": "Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1", "gene_name": "PPP1R15B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q5SWA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126482" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycoprotein; glycosylation may affect nuclear localization.", "mechanism": "SMAD2 locus associated with asthma; involved in TGF-\u03b2 signaling and airway remodeling.", "protein": "SMAD2", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15796" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12126482" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "IL-13 is a glycoprotein; glycosylation affects receptor binding.", "mechanism": "IL13 locus associated with asthma and eosinophil counts; key cytokine in Th2 inflammation.", "protein": "IL13", "protein_enriched": { "function": "Cytokine that plays important roles in allergic inflammation and immune response to parasite infection (PubMed:8096327, PubMed:8097324). Synergizes with IL2 in regulating interferon-gamma synthesis (P", "gene_name": "IL13", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35225" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12126482" }, { "confidence": "high", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "PD-L1 is targeted by toripalimab (anti-PD-L1 antibody) to enhance antitumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126510" }, { "confidence": "high", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "PD-1 is glycosylated, which can modulate ligand binding and immune signaling.", "mechanism": "PD-1 on T cells is targeted by immune checkpoint inhibitors to restore T cell function.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "CD3 is a glycoprotein; glycosylation may affect T cell receptor function.", "mechanism": "CD3+ T cell infiltration in tumor microenvironment correlates with response to therapy.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "CD8 is glycosylated, influencing T cell activation.", "mechanism": "PD-1+ CD8+ T cell enrichment in responders indicates effective antitumor immunity.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect B cell signaling.", "mechanism": "CD20+ B cell infiltration is associated with better response to therapy.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "CD56 is heavily glycosylated, modulating NK cell interactions.", "mechanism": "CD56dim NK cell enrichment in responders suggests enhanced innate immunity.", "protein": "CD56", "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Advanced Gastric Cancer (AGC)", "glycan_involvement": "MMR proteins are glycoproteins; glycosylation may affect protein stability.", "mechanism": "Proficient MMR (pMMR) status was present in all patients; MMR status predicts immunotherapy response.", "protein": "MMR proteins (e.g., MLH1, MSH2)", "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Gastric cancer with poor performance status (PS 2)", "glycan_involvement": "Glycosylation of PD-L1 may mask antibody binding and affect detection.", "mechanism": "PD-L1 expression (CPS \u22651) was not predictive of response in this PS 2 cohort.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "medium", "disease": "Gastric cancer with poor performance status (PS 2)", "glycan_involvement": "Glycosylation may regulate PD-1 surface expression.", "mechanism": "PD-1+ T cell infiltration was higher in responders, indicating immune activation.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "low", "disease": "Liver metastasis in gastric cancer", "glycan_involvement": "CD8 glycosylation may affect T cell migration and function.", "mechanism": "Lower CD8+ T cell infiltration associated with liver metastasis and reduced response.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126510" }, { "confidence": "high", "disease": "Tongue squamous cell carcinoma (TSCC)", "glycan_involvement": "LAMP3 is a highly glycosylated lysosomal membrane protein; glycosylation is essential for its stability and function.", "mechanism": "LAMP3 overexpression promotes proliferation, DNA replication, metastasis, and metabolic reprogramming (glycolysis up, gluconeogenesis down) in TSCC cells.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "causal", "source_pmcid": "PMC12126571" }, { "confidence": "high", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "Glycosylation of LAMP3 is required for its membrane localization and function.", "mechanism": "High LAMP3 expression is an independent prognostic biomarker for poor survival.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Laryngeal squamous cell carcinoma", "glycan_involvement": "LAMP3 glycosylation may affect its interaction with ECM glycoproteins (LAMC2, TNC).", "mechanism": "High LAMP3 expression predicts poor prognosis; LAMP3 downregulation enhances radiation response via LAMP3/LAMC2/TNC pathway.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation of LAMP3 likely mediates its role in cell adhesion and signaling.", "mechanism": "LAMP3 upregulation (via RPL21/TFEB) promotes invasion/metastasis through FAK/paxillin/ERK pathway.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "causal", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Glycosylation may regulate LAMP3's membrane localization and downstream signaling.", "mechanism": "LAMP3 deficiency increases PKA-mediated VASP phosphorylation, suppressing invasion/metastasis.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "protective (when downregulated)", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation likely required for LAMP3 function in signaling.", "mechanism": "LAMP3 promotes invasion/metastasis via SPP1 signaling.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "causal", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Laryngeal squamous cell carcinoma", "glycan_involvement": "LAMC2 is a glycoprotein; glycosylation is essential for ECM interactions.", "mechanism": "LAMC2 acts downstream of LAMP3 in promoting tumor progression.", "protein": "LAMC2", "protein_enriched": { "function": "Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other ext", "gene_name": "LAMC2", "glycan_count": 7, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G06110VR", "G37995HC", "G70223PD", "G83460ZZ", "G84452RH", "G87389XI" ], "uniprot_id": "Q13753" }, "relationship_type": "causal (in pathway)", "source_pmcid": "PMC12126571" }, { "confidence": "medium", "disease": "Laryngeal squamous cell carcinoma", "glycan_involvement": "TNC is a glycoprotein; glycosylation modulates cell adhesion.", "mechanism": "TNC acts downstream of LAMP3 in promoting tumor progression.", "protein": "TNC", "relationship_type": "causal (in pathway)", "source_pmcid": "PMC12126571" }, { "confidence": "high", "disease": "Tongue squamous cell carcinoma (TSCC)", "glycan_involvement": "Targeting glycosylated LAMP3 may disrupt its function.", "mechanism": "LAMP3 knockdown suppresses tumor growth, proliferation, metastasis, and metabolic reprogramming in vitro and in vivo.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126571" }, { "confidence": "high", "disease": "Tongue squamous cell carcinoma (TSCC)", "glycan_involvement": "Glycosylation status may enhance detection as a biomarker.", "mechanism": "LAMP3 is overexpressed in TSCC tissues and cells compared to normal controls.", "protein": "LAMP3", "protein_enriched": { "function": "5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts", "gene_name": "EXO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UQ84" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126571" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and regulates its cell surface expression.", "mechanism": "PD-L1 on MDSCs mediates immune suppression and resistance to anti-PD-1 therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "high", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "Glycosylation required for VISTA surface expression and ligand binding.", "mechanism": "VISTA highly expressed on MDSCs suppresses CD8+ T cell activity; knockdown reduces immunosuppression.", "protein": "VISTA", "protein_enriched": { "function": "Cell surface glycoprotein involved in various biological processes including angiogenesis, immune response modulation, and tissue remodeling and repair. Participates in pericyte proliferation through ", "gene_name": "CD248", "glycan_count": 5, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57317CE", "G49108TO" ], "uniprot_id": "Q9HCU0" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation modulates protein stability and receptor interaction.", "mechanism": "S100A8/A9 promotes MDSC migration and immunosuppression via NF-\u03baB signaling.", "protein": "S100A8/A9 (calprotectin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Sialic acid-binding domain mediates immune cell interactions.", "mechanism": "High CD33+ MDSC levels correlate with poor prognosis and reduced survival.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126600" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects integrin-mediated adhesion and migration.", "mechanism": "CD11b+ MDSCs promote metastasis and correlate with aggressive disease.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12126600" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation required for LPS binding and signaling.", "mechanism": "CD14+ MDSCs secrete TGF-\u03b2, suppressing T cell function and correlating with disease progression.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126600" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Sialyl-Lewis X glycan mediates cell-cell interactions.", "mechanism": "CD15+ MDSCs overexpress Arg1, mediating T cell suppression.", "protein": "CD15", "relationship_type": "biomarker", "source_pmcid": "PMC12126600" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "IL-4R\u03b1+ MDSCs secrete IDO, promoting Treg expansion and immune evasion.", "protein": "IL-4R\u03b1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates VEGF-A secretion and receptor binding.", "mechanism": "VEGF-A secreted by tumor cells recruits MDSCs, promoting angiogenesis and metastasis.", "protein": "VEGF-A", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation required for receptor trafficking and ligand binding.", "mechanism": "CCR5+ MDSCs accumulate in tumors, promoting progression; antagonists reduce tumor growth.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126600" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "HER2 is a glycoprotein; glycosylation affects receptor stability and signaling.", "mechanism": "HER2 mutations drive oncogenesis and tumor progression in NSCLC.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "causal", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Brain metastases in NSCLC", "glycan_involvement": "Glycosylation may influence HER2-mediated cell adhesion and migration.", "mechanism": "HER2 mutations are associated with increased risk of brain metastases in NSCLC.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "causal", "source_pmcid": "PMC12126673" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation can modulate antibody binding and drug efficacy.", "mechanism": "HER2 is targeted by TKIs and antibody-drug conjugates for NSCLC therapy.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "VEGF glycosylation affects secretion and receptor interaction.", "mechanism": "VEGF promotes angiogenesis in NSCLC; targeted by anti-angiogenic therapies.", "protein": "VEGF (Vascular Endothelial Growth Factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may affect detection and diagnostic assays.", "mechanism": "HER2 mutation status guides selection of targeted therapies.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "biomarker", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may influence immune recognition and drug response.", "mechanism": "Combination therapies (chemotherapy, immunotherapy, anti-angiogenic) improve outcomes in HER2-mutated NSCLC.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Brain metastases in NSCLC", "glycan_involvement": "Glycosylation impacts VEGF function and therapeutic antibody binding.", "mechanism": "Anti-angiogenic therapy targeting VEGF improves progression-free survival in NSCLC patients with brain metastases.", "protein": "VEGF (Vascular Endothelial Growth Factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "HER2 glycosylation affects ADC binding and internalization.", "mechanism": "Antibody-drug conjugates (e.g., trastuzumab deruxtecan) target HER2 for NSCLC treatment.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may modulate HER2 immunogenicity and drug response.", "mechanism": "Combination of chemotherapy, immunotherapy, and anti-angiogenic therapy (C + I + A) yields best outcomes for HER2-mutated NSCLC.", "protein": "HER2 (Human Epidermal Growth Factor Receptor 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126673" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation status may affect VEGF detection and function.", "mechanism": "VEGF expression indicates angiogenic activity and guides anti-angiogenic therapy.", "protein": "VEGF (Vascular Endothelial Growth Factor)", "relationship_type": "biomarker", "source_pmcid": "PMC12126673" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "UCP1 is glycosylated, which may affect its stability and activity in adipocytes.", "mechanism": "Pep19 activates UCP1, promoting browning of white adipose tissue and visceral fat reduction.", "protein": "UCP1", "protein_enriched": { "function": "Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and", "gene_name": "UCP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126752" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "CB1R glycosylation affects receptor trafficking and ligand binding.", "mechanism": "Pep19 acts as an inverse agonist at CB1R, modulating adipocyte metabolism and reducing visceral fat.", "protein": "CB1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126752" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "GLP-1R glycosylation is critical for receptor function and cell surface expression.", "mechanism": "GLP-1R agonists reduce body weight and improve metabolic parameters; Pep19 may have indirect effects.", "protein": "GLP-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126752" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "DP IV is heavily glycosylated, influencing enzymatic activity and stability.", "mechanism": "DP IV cleaves GLP-1, regulating its activity; Pep19 does not competitively inhibit DP IV, minimizing indirect GLP-1 effects.", "protein": "DP IV/CD26", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126752" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "CRP glycosylation modulates its immunological activity.", "mechanism": "CRP levels reflect systemic inflammation associated with visceral fat and metabolic disease.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126752" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Insulin glycosylation affects secretion and receptor interaction.", "mechanism": "Pep19 improves insulin sensitivity in animal models, potentially reducing insulin resistance.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126752" }, { "confidence": "low", "disease": "Non-alcoholic Fatty Liver Disease", "glycan_involvement": "ALT glycosylation can affect enzyme activity.", "mechanism": "ALT elevation may indicate liver injury; Pep19 may improve liver function, but further study needed.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126752" }, { "confidence": "low", "disease": "Non-alcoholic Fatty Liver Disease", "glycan_involvement": "AST glycosylation can affect enzyme activity.", "mechanism": "AST elevation may indicate liver injury; Pep19 may improve liver function, but further study needed.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12126752" }, { "confidence": "medium", "disease": "Sleep Disturbance", "glycan_involvement": "Glycosylation may modulate UCP1 function in adipocytes.", "mechanism": "Pep19-induced UCP1 activation reduces visceral fat, which is linked to improved sleep quality.", "protein": "UCP1", "protein_enriched": { "function": "Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and", "gene_name": "UCP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25874" }, "relationship_type": "protective", "source_pmcid": "PMC12126752" }, { "confidence": "medium", "disease": "Sleep Disturbance", "glycan_involvement": "CB1R glycosylation affects receptor function.", "mechanism": "CB1R modulation by Pep19 may indirectly improve sleep via metabolic effects.", "protein": "CB1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126752" }, { "confidence": "high", "disease": "Liver failure", "glycan_involvement": "N-glycosylation affects albumin stability and half-life.", "mechanism": "Low serum albumin indicates impaired liver synthetic function post-hepatectomy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Cardiac dysfunction", "glycan_involvement": "BNP is O-glycosylated, affecting secretion and clearance.", "mechanism": "Elevated BNP reflects cardiac stress or dysfunction perioperatively.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Coagulation disorder", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Prolonged PT indicates impaired coagulation, risk of bleeding.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "medium", "disease": "Hemorrhage", "glycan_involvement": "Glycosylation modulates platelet adhesion and aggregation.", "mechanism": "Platelet glycoproteins mediate aggregation; dysfunction increases bleeding risk.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12126887" }, { "confidence": "medium", "disease": "Liver failure", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "Elevated ALT signals hepatocellular injury post-resection.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "medium", "disease": "Cardiac dysfunction", "glycan_involvement": "Glycosylation influences enzyme clearance.", "mechanism": "Elevated CK-MB indicates myocardial injury perioperatively.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Cardiac dysfunction", "glycan_involvement": "Glycosylation affects troponin stability and detection.", "mechanism": "Elevated cTn is a sensitive marker of myocardial injury.", "protein": "Cardiac troponin (cTn)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "medium", "disease": "Coagulation disorder", "glycan_involvement": "Glycosylation of clotting factors affects TEG results.", "mechanism": "TEG measures clot formation; abnormal results indicate coagulopathy.", "protein": "TEG glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Biliary leakage", "glycan_involvement": "Glycoprotein-mediated conjugation required for bilirubin excretion.", "mechanism": "Elevated drainage bilirubin signals bile leak post-hepatectomy.", "protein": "Total bilirubin (conjugated by glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Coagulation disorder", "glycan_involvement": "Glycosylation required for factor secretion and function.", "mechanism": "Prolonged APTT indicates intrinsic pathway dysfunction.", "protein": "APTT factors", "relationship_type": "biomarker", "source_pmcid": "PMC12126887" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "PCSK9 is glycosylated, affecting its stability and secretion.", "mechanism": "PCSK9 promotes LDL receptor degradation, increasing LDL cholesterol; siRNA targeting PCSK9 reduces LDL-C.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "APOC3 is glycosylated, influencing its interaction with lipoproteins.", "mechanism": "APOC3 inhibits lipoprotein lipase, raising triglyceride-rich lipoproteins; siRNA silencing APOC3 lowers triglycerides.", "protein": "APOC3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "high", "disease": "Hyperlipoproteinemia(a)", "glycan_involvement": "LPA contains extensive O-glycosylation in its kringle domains, affecting its plasma levels.", "mechanism": "LPA is a major carrier of cholesterol; siRNA targeting LPA reduces apolipoprotein(a) and associated cholesterol.", "protein": "LPA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "high", "disease": "Mixed hyperlipidemia", "glycan_involvement": "ANGPTL3 is glycosylated, modulating its secretion and activity.", "mechanism": "ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, increasing triglycerides and cholesterol; siRNA silencing lowers lipid levels.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "high", "disease": "Chylomicronemia", "glycan_involvement": "Glycosylation affects APOC3's interaction with chylomicrons.", "mechanism": "APOC3 inhibition enhances chylomicron clearance; siRNA therapy reduces apolipoprotein and triglyceride levels.", "protein": "APOC3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation of LPA modulates its atherogenicity.", "mechanism": "Elevated LPA is a risk factor for atherosclerosis due to its pro-inflammatory and pro-thrombotic properties.", "protein": "LPA", "relationship_type": "causal", "source_pmcid": "PMC12126973" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "Glycosylation regulates ANGPTL3 stability and function.", "mechanism": "ANGPTL3 inhibition increases lipase activity, lowering triglycerides.", "protein": "ANGPTL3", "protein_enriched": { "function": "Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis", "gene_name": "ANGPT4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q9Y264" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects PCSK9's secretion and activity.", "mechanism": "PCSK9-mediated LDL receptor degradation increases LDL-C, promoting atherosclerosis.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12126973" }, { "confidence": "medium", "disease": "Mixed hyperlipidemia", "glycan_involvement": "Glycosylation modulates APOC3's lipoprotein binding.", "mechanism": "APOC3 silencing reduces both triglycerides and apolipoproteins in mixed dyslipidemia.", "protein": "APOC3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126973" }, { "confidence": "medium", "disease": "Hypercholesterolemia", "glycan_involvement": "O-glycosylation impacts LPA's plasma concentration.", "mechanism": "Elevated LPA is associated with increased cholesterol and cardiovascular risk.", "protein": "LPA", "relationship_type": "biomarker", "source_pmcid": "PMC12126973" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "NGAL is released during kidney injury and is elevated in plasma/urine during SA-AKI.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "IL-18 is glycosylated, which may affect secretion and activity.", "mechanism": "Urinary IL-18 is elevated in SA-AKI, reflecting inflammatory kidney injury.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "CRP is glycosylated; glycan structure influences immune recognition.", "mechanism": "CRP is elevated in systemic inflammation and correlates with SA-AKI severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "Not a glycoprotein; no glycosylation.", "mechanism": "Elevated serum 5-MTP is associated with better renal recovery and lower mortality in SA-AKI; low levels predict poor prognosis.", "protein": "5-Methoxytryptophan (5-MTP)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12126981" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Not a glycoprotein; no glycosylation.", "mechanism": "Higher 5-MTP levels correlate with improved survival and reduced inflammation in sepsis.", "protein": "5-Methoxytryptophan (5-MTP)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12126981" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Not a glycoprotein; no glycosylation.", "mechanism": "Decreased serum 5-MTP is observed in CKD patients, indicating impaired renal function.", "protein": "5-Methoxytryptophan (5-MTP)", "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "Not a glycoprotein; no glycosylation.", "mechanism": "Serum 5-MTP positively correlates with disease activity and prognosis in LN.", "protein": "5-Methoxytryptophan (5-MTP)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12126981" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "PCT is glycosylated; glycosylation may affect its clearance and detection.", "mechanism": "Elevated PCT is an independent predictor of SA-AKI occurrence and severity.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects receptor binding and activity.", "mechanism": "IL-6 is elevated in SA-AKI and correlates with inflammation and poor prognosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "Cys-C is glycosylated; glycosylation affects stability and renal clearance.", "mechanism": "Cys-C is elevated in SA-AKI and reflects impaired glomerular filtration.", "protein": "Cystatin C (Cys-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12126981" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-6 is N-glycosylated, which affects its stability and secretion.", "mechanism": "Elevated IL-6 reflects hyperinflammation and immune dysregulation in sepsis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Multiple Organ Dysfunction Syndrome (MODS)", "glycan_involvement": "Glycosylation modulates IL-6 bioactivity and receptor interactions.", "mechanism": "High IL-6 levels drive cytokine storm, leading to organ dysfunction.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12126990" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation influences IL-6 stability in circulation.", "mechanism": "IL-6/LY ratio predicts prognosis in COVID-19, reflecting immune dysregulation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Glycosylation affects IL-6 secretion and half-life.", "mechanism": "IL-6 elevation indicates systemic inflammation and poor prognosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "medium", "disease": "Acute Organ Failure", "glycan_involvement": "N-glycosylation required for proper IL-6 function.", "mechanism": "IL-6-driven inflammation contributes to acute organ failure in critical illness.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12126990" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation status may affect therapeutic antibody binding.", "mechanism": "Targeting IL-6 may modulate hyperinflammation and improve outcomes.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-6 glycosylation affects its serum levels and detection.", "mechanism": "IL-6/LY ratio integrates inflammation and immune suppression for risk stratification.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Multiple Organ Dysfunction Syndrome (MODS)", "glycan_involvement": "Glycosylation influences IL-6 receptor binding and downstream signaling.", "mechanism": "IL-6/LY ratio predicts MODS development in sepsis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation is essential for IL-6 secretion and activity.", "mechanism": "IL-6 promotes lymphocyte apoptosis and immune cell overactivation via JAK/STAT3 pathway.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect IL-6 detection and quantification in clinical assays.", "mechanism": "Persistent elevation of IL-6/LY ratio is associated with increased 28-day mortality.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12126990" }, { "confidence": "high", "disease": "Acute liver allograft rejection", "glycan_involvement": "Glycosylation required for proper surface expression and immune synapse formation.", "mechanism": "Upregulated on dendritic cells during YY1 overexpression, promoting T cell activation and rejection.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). 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May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "high", "disease": "Acute liver allograft rejection", "glycan_involvement": "N-glycosylation affects peptide loading and T cell recognition.", "mechanism": "Increased expression on DCs drives antigen presentation to T cells, leading to rejection.", "protein": "MHC II", "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "high", "disease": "Acute liver allograft rejection", "glycan_involvement": "No direct glycosylation; acts as transcriptional regulator of glycoprotein genes.", "mechanism": "YY1 upregulation in DCs triggers their maturation and inflammatory cytokine production, promoting T cell polarization to Th1/Th17.", "protein": "YY1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Acute liver allograft rejection", "glycan_involvement": "Glycosylation influences secretion and receptor binding.", "mechanism": "Secreted by YY1-activated DCs, amplifies inflammation and tissue injury.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Acute liver allograft rejection", "glycan_involvement": "Glycosylation required for stability and activity.", "mechanism": "Produced by mature DCs, promotes Th17 differentiation and rejection.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Acute liver allograft rejection", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "Produced by Th1 cells polarized by YY1-activated DCs, mediates graft injury.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Acute liver allograft rejection", "glycan_involvement": "Glycosylation required for cytokine function.", "mechanism": "Produced by Th17 cells induced by YY1-activated DCs, drives inflammation.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Indirect; regulates glycoprotein cytokine genes.", "mechanism": "YY1 promotes pathogenic Th17 differentiation via T-bet interaction.", "protein": "YY1", "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Indirect; regulates glycoprotein cytokine genes.", "mechanism": "YY1 reduces Foxp3 in Tregs, impairing immune suppression.", "protein": "YY1", "relationship_type": "causal", "source_pmcid": "PMC12127155" }, { "confidence": "high", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation affects membrane localization and transporter activity.", "mechanism": "Regulates bile acid transport and homeostasis, protecting against hepatic lipid accumulation.", "protein": "ABCC3", "protein_enriched": { "function": "Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during developme", "gene_name": "Pitx3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O35160" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127171" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation modulates lipid binding and plasma stability.", "mechanism": "Promotes cholesterol efflux, reducing serum lipid levels.", "protein": "APOA2", "relationship_type": "biomarker", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation influences lipoprotein interactions.", "mechanism": "Regulates cholesterol metabolism and efflux.", "protein": "APOC1", "relationship_type": "biomarker", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation affects receptor interaction and downstream signaling.", "mechanism": "Modulates insulin signaling; restoration improves insulin sensitivity.", "protein": "IRS3", "relationship_type": "causal", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Regulates liver insulin sensitivity; upregulation improves glucose metabolism.", "protein": "PRLR", "protein_enriched": { "function": "This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and st", "gene_name": "PRLR", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P16471" }, "relationship_type": "protective", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Estrogen catabolism via SULT1E1 interacts with PPAR\u03b3, contributing to atherosclerosis.", "protein": "SULT1E1", "relationship_type": "causal", "source_pmcid": "PMC12127171" }, { "confidence": "high", "disease": "Bile Acid Dysregulation", "glycan_involvement": "Glycosylation modulates enzyme stability.", "mechanism": "Key enzyme in bile acid synthesis; regulation restores bile acid homeostasis.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "Glycosylation required for enzymatic activity.", "mechanism": "Facilitates detoxification and bile acid conjugation, protecting liver cells.", "protein": "UGT1A6", "protein_enriched": { "function": "UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to facilitate their inactivation and excretion ", "gene_name": "UGT1A6", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G14669DU", "G39188ZX" ], "uniprot_id": "P19224" }, "relationship_type": "protective", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Regulates fatty acid uptake and bile acid synthesis, reducing hepatic lipid accumulation.", "protein": "SLC27A5", "relationship_type": "protective", "source_pmcid": "PMC12127171" }, { "confidence": "medium", "disease": "Bile Acid Dysregulation", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Involved in alternative bile acid synthesis; regulation improves bile acid balance.", "protein": "CYP7B1", "protein_enriched": { "function": "P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholest", "gene_name": "CYP46A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6A2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127171" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its isoforms and detection.", "mechanism": "Elevated AFP (>400 ng/mL) is associated with diagnosis and increased risk of early recurrence after hepatectomy.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12127185" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP-L3 is a glycosylated isoform; glycosylation enables its specific detection and functional differences.", "mechanism": "AFP-L3 positivity correlates with poor differentiation, vascular invasion, and higher risk of recurrence.", "protein": "AFP-L3", "relationship_type": "biomarker", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Early recurrence after hepatectomy", "glycan_involvement": "VEGF is glycosylated; glycosylation modulates its stability and receptor interactions.", "mechanism": "Released by damaged LSECs, VEGF increases vascular permeability, facilitating tumor cell extravasation and metastasis.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "causal", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Early recurrence after hepatectomy", "glycan_involvement": "ANGPT2 is glycosylated; glycosylation affects its secretion and activity.", "mechanism": "ANGPT2 released from damaged LSECs increases vascular permeability, promoting intrahepatic metastasis.", "protein": "Angiopoietin-2 (ANGPT2)", "relationship_type": "causal", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycan involvement mentioned.", "mechanism": "HBx upregulates DNA methyltransferases, suppressing tumor suppressor genes and promoting carcinogenesis.", "protein": "HBx protein", "relationship_type": "causal", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "SLC7A11 is glycosylated; glycosylation may affect transporter function.", "mechanism": "Upregulation of SLC7A11 reduces ferroptosis, enhancing tumor cell survival under oxidative stress.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD133 is heavily glycosylated; glycosylation is essential for its cell surface localization and stem cell marker function.", "mechanism": "CD133+ liver cancer cells maintain stemness, promote chemoresistance, and enhance invasiveness via EMT and angiogenic factor secretion.", "protein": "CD133 (Prominin-1)", "relationship_type": "causal", "source_pmcid": "PMC12127185" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NKG2D is glycosylated; glycosylation affects receptor stability and ligand binding.", "mechanism": "NKG2D mediates immune surveillance; its downregulation in chronic liver disease impairs antitumor immunity.", "protein": "NKG2D", "protein_enriched": { "function": "Involved in pre-mRNA splicing process (PubMed:11991638, PubMed:12084575, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre", "gene_name": "CRNKL1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10488MI", "G49108TO" ], "uniprot_id": "Q9BZJ0" }, "relationship_type": "protective", "source_pmcid": "PMC12127185" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "SPINK1 is glycosylated; glycosylation may affect its secretion and activity.", "mechanism": "SPINK1 signaling supports stemness and chemoresistance in CD133+ liver cancer cells.", "protein": "SPINK1", "protein_enriched": { "function": "V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted", "gene_name": "IGKV2-30", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06310" }, "relationship_type": "causal", "source_pmcid": "PMC12127185" }, { "confidence": "high", "disease": "Early recurrence after hepatectomy", "glycan_involvement": "AFP-L3 glycosylation enables its specific detection and functional differences from total AFP.", "mechanism": "AFP-L3 positivity is associated with increased risk of early postoperative recurrence.", "protein": "AFP-L3", "relationship_type": "biomarker", "source_pmcid": "PMC12127185" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "Keratin glycosylation may affect stability and immune recognition.", "mechanism": "High baseline plasma K2C5 predicts strong clinical response to NuGel (GPCR19 agonist) in AD patients.", "protein": "K2C5", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "ENTP6 is a glycoprotein; glycosylation may regulate its enzymatic activity.", "mechanism": "Low baseline ENTP6 predicts favorable response to NuGel in AD.", "protein": "ENTP6", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "CRK is glycosylated; glycosylation may modulate signaling.", "mechanism": "Low baseline CRK predicts favorable response to NuGel in AD.", "protein": "CRK", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Immunoglobulin glycosylation affects immune effector function.", "mechanism": "High baseline IGHA2 associated with better response to NuGel.", "protein": "IGHA2", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "SMOC1 is glycosylated; glycosylation may affect cell-matrix interactions.", "mechanism": "High baseline SMOC1 associated with better response to NuGel.", "protein": "SMOC1", "protein_enriched": { "function": "Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation", "gene_name": "SMOC1", "glycan_count": 9, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT", "G57321FI", "G43417UB", "G53434XO", "G00912UN", "G02815KT", "G27058EU", "G61256FT", "G76295SF" ], "uniprot_id": "Q9H4F8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Complement proteins are heavily glycosylated, affecting activation and clearance.", "mechanism": "Complement activation pathway enriched in responders; complement activity linked to AD inflammation.", "protein": "Complement proteins", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation modulates inhibitor stability and function.", "mechanism": "Protease inhibitor pathway enriched in responders; may regulate inflammation and skin barrier.", "protein": "Protease inhibitors", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation mediates heparin binding and function.", "mechanism": "Enriched in responders; HBPs modulate inflammation and vascular leakage in AD.", "protein": "Heparin-binding proteins", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Fc glycosylation critical for effector function.", "mechanism": "Immunoglobulin levels (e.g., IGHA2) associated with response to therapy.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation regulates cell-cell and cell-matrix adhesion.", "mechanism": "Cell adhesion pathway proteins predict response to NuGel.", "protein": "Cell adhesion molecules", "relationship_type": "biomarker", "source_pmcid": "PMC12127193" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Sortilin is glycosylated, which affects its trafficking and receptor function.", "mechanism": "Elevated serum Sortilin correlates with GDM risk in PCOS, likely via modulation of glucose and lipid metabolism and insulin signaling.", "protein": "Sortilin", "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "N-glycosylation regulates Sortilin's cell surface expression and function.", "mechanism": "Sortilin overexpression exacerbates insulin resistance by affecting GLUT4 trafficking in adipocytes and muscle cells.", "protein": "Sortilin", "relationship_type": "causal", "source_pmcid": "PMC12127198" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "HMGB1 secretion and extracellular activity are modulated by glycosylation.", "mechanism": "Elevated HMGB1 independently predicts GDM in PCOS pregnancies; acts via proinflammatory signaling and impairment of insulin signaling.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation influences HMGB1 release and immune recognition.", "mechanism": "HMGB1 activates TLR4/NF-\u03baB pathway, promoting inflammation and insulin resistance.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Glycosylation may affect HMGB1's extracellular signaling.", "mechanism": "Elevated HMGB1 reflects chronic low-grade inflammation in PCOS.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "GALP glycosylation may affect peptide stability and receptor interaction.", "mechanism": "Elevated GALP independently predicts GDM in PCOS pregnancies; influences insulin sensitivity and energy metabolism.", "protein": "Galanin-like peptide (GALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation may regulate GALP's bioactivity.", "mechanism": "GALP modulates insulin sensitivity in adipose and muscle tissue; deficiency exacerbates glucose intolerance.", "protein": "Galanin-like peptide (GALP)", "relationship_type": "causal", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Sortilin glycosylation affects its metabolic functions.", "mechanism": "Elevated Sortilin is associated with diabetes onset via effects on glucose and lipid metabolism.", "protein": "Sortilin", "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates Sortilin's receptor activity.", "mechanism": "Sortilin regulates arterial wall inflammation and calcification, contributing to cardiovascular risk.", "protein": "Sortilin", "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects HMGB1's extracellular signaling.", "mechanism": "HMGB1 promotes \u03b2-cell dysfunction and insulin resistance, contributing to diabetes pathogenesis.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127198" }, { "confidence": "high", "disease": "Central nervous system toxicity", "glycan_involvement": "N-glycosylation critical for P-gp function and trafficking.", "mechanism": "Inhibition of P-gp by co-medications increases linezolid CNS levels, raising neurotoxicity risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "high", "disease": "Serotonin syndrome", "glycan_involvement": "Glycosylation affects MAOA stability and localization.", "mechanism": "Linezolid inhibits MAOA, leading to serotonin accumulation and toxicity.", "protein": "Monoamine oxidase A (MAOA)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metaboli", "gene_name": "MAOA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21397" }, "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Myelin glycoprotein integrity is essential for nerve conduction.", "mechanism": "Linezolid-induced mitochondrial dysfunction damages myelin and axons.", "protein": "Myelin basic protein", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Central nervous system toxicity", "glycan_involvement": "Receptor glycosylation modulates immune signaling.", "mechanism": "Adalimumab (anti-TNF-\u03b1) increases susceptibility to neurotoxicity with linezolid.", "protein": "TNF-\u03b1 receptor", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Seizures", "glycan_involvement": "Glycosylation affects receptor function and pharmacology.", "mechanism": "Moxifloxacin inhibits GABA-A, increasing seizure risk with linezolid.", "protein": "GABA-A receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "high", "disease": "Serotonin syndrome", "glycan_involvement": "Glycosylation regulates SERT trafficking and function.", "mechanism": "SSRIs/SNRIs with linezolid increase serotonin, causing toxicity.", "protein": "Serotonin transporter (SERT)", "protein_enriched": { "function": "Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the ", "gene_name": "SLC6A4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31645" }, "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycoprotein assembly critical for mitochondrial function.", "mechanism": "Linezolid inhibits mitochondrial protein synthesis, damaging optic nerve.", "protein": "Mitochondrial respiratory chain complexes", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Essential for axonal maintenance and signal transduction.", "mechanism": "Linezolid-induced mitochondrial dysfunction impairs optic nerve glycoproteins.", "protein": "Optic nerve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Glycosylation modulates channel gating and localization.", "mechanism": "Linezolid increases calcium influx, leading to axonal damage.", "protein": "Voltage-gated calcium channel", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "medium", "disease": "Polyneuropathy", "glycan_involvement": "Glycosylation required for nerve structure and repair.", "mechanism": "Linezolid-induced mitochondrial toxicity disrupts peripheral nerve glycoproteins.", "protein": "Peripheral nerve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12127208" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects CD36 trafficking and function.", "mechanism": "Elevated hepatic CD36 promotes lipogenesis and steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates FABP1 stability and ligand binding.", "mechanism": "FABP1 upregulation aids fatty acid trafficking and protects from lipotoxicity.", "protein": "FABP1", "protein_enriched": { "function": "Plays a role in lipoprotein-mediated cholesterol uptake in hepatocytes (PubMed:25732850). Binds cholesterol (PubMed:25732850). Binds free fatty acids and their coenzyme A derivatives, bilirubin, and s", "gene_name": "FABP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07148" }, "relationship_type": "protective", "source_pmcid": "PMC12127212" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation critical for collagen fibril formation.", "mechanism": "COL1A1 upregulation marks collagen deposition and fibrosis.", "protein": "COL1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects actin polymerization.", "mechanism": "\u03b1SMA marks stellate cell activation and fibrogenesis.", "protein": "\u03b1SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12127212" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation regulates TNF-alpha secretion and receptor binding.", "mechanism": "TNF-alpha upregulation drives hepatic inflammation in MASH.", "protein": "TNF-alpha", "relationship_type": "causal", "source_pmcid": "PMC12127212" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation modulates IL-6 stability and activity.", "mechanism": "IL-6 upregulation contributes to hepatic inflammatory milieu.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation affects IFN-\u03b3 receptor interactions.", "mechanism": "IFN-\u03b3 upregulation enhances hepatic immune response.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "Lymphoid hyperplasia", "glycan_involvement": "Glycosylation required for TCR complex assembly.", "mechanism": "CD3e marks T-cell infiltration in hepatic lymphoid follicles.", "protein": "CD3e", "relationship_type": "biomarker", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "Lymphoid hyperplasia", "glycan_involvement": "Glycosylation modulates CD19 signaling.", "mechanism": "CD19 marks B-cell infiltration in hepatic lymphoid follicles.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127212" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation influences NOX2 complex assembly.", "mechanism": "CYBB upregulation indicates phagocyte activation in hepatic inflammation.", "protein": "CYBB (NOX2)", "relationship_type": "biomarker", "source_pmcid": "PMC12127212" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation affects P-glycoprotein stability and drug transport function.", "mechanism": "P-glycoprotein modulates drug efflux, affecting BRAF/MEK inhibitor bioavailability and efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127241" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation influences CYP enzyme folding and activity.", "mechanism": "CYPs metabolize BRAF/MEK inhibitors; DDIs via CYP modulation alter drug levels and outcomes.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Not specified in article.", "mechanism": "Mutant BRAF (V600E) drives melanoma; targeted by BRAF inhibitors.", "protein": "BRAF", "protein_enriched": { "function": "Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathw", "gene_name": "BRAF", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15056" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127241" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Not specified in article.", "mechanism": "MEK1/2 are downstream of BRAF; MEK inhibitors delay resistance.", "protein": "MEK1/2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127241" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Glycosylation modulates efflux efficiency.", "mechanism": "P-glycoprotein-mediated efflux reduces intracellular drug concentration, promoting resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "medium", "disease": "Cardiovascular toxicity", "glycan_involvement": "Glycosylation affects CYP stability and interaction with drugs.", "mechanism": "DDIs affecting CYPs can increase drug toxicity, including cardiovascular events.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "medium", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation required for proper transporter function.", "mechanism": "ABC transporters influence drug disposition and efficacy.", "protein": "ATP-binding cassette transporters", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127241" }, { "confidence": "low", "disease": "Squamous cell carcinoma", "glycan_involvement": "Glycosylation may affect CYP-mediated metabolic activation.", "mechanism": "Paradoxical activation via DDIs may promote secondary carcinoma.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "medium", "disease": "Progressive disease", "glycan_involvement": "Glycosylation status impacts activity.", "mechanism": "High P-glycoprotein activity may reduce efficacy of therapy, leading to progression.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Induction/inhibition of CYPs by DDIs alters drug metabolism, contributing to resistance.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "causal", "source_pmcid": "PMC12127241" }, { "confidence": "high", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "CLDN18 is a glycoprotein involved in ADCP regulation.", "mechanism": "Elevated CLDN18 promotes malignant capability; suppression reduces tumor cell malignancy.", "protein": "CLDN18", "protein_enriched": { "function": "Receptor that may have an important role in cell/cell signaling during nervous system formation", "gene_name": "CELSR1", "glycan_count": 46, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G30970QQ", "G31852PQ", "G41247ZX", "G62765YT", "G64527OM", "G77669RF", "G80920RR", "G07246CJ", "G07755XJ", "G08918WF", "G14972EH", "G27058EU", "G41071NU", "G43223CG", "G79666IR", "G87661QW", "G28681TP", "G63980BQ", "G70101JE", "G83460ZZ", "G49108TO", "G02815KT", "G10486CT", "G59626AS", "G65184UU", "G70619PT", "G72790NZ", "G04657PL", "G39446WN", "G45395BF", "G48584BU", "G57776ZS", "G68490OW", "G70441OD", "G70822IO", "G83646BJ", "G85282JO", "G90659AW", "G27915IV", "G72797UR", "G53434XO", "G29068FM", "G43417UB", "G57321FI", "G15664MX", "G72667IM" ], "uniprot_id": "Q9NYQ6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma (LIHC)", "glycan_involvement": "GYPA is a sialoglycoprotein, likely involved in immune cell recognition.", "mechanism": "Elevated in LIHC tissues and cells; potential ADCP regulatory role.", "protein": "GYPA", "relationship_type": "biomarker", "source_pmcid": "PMC12127322" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "MGAT1 mediates N-glycosylation, affecting immune cell function.", "mechanism": "Controls glycosylation in macrophages, influencing tumor growth and prognosis.", "protein": "MGAT1", "relationship_type": "causal", "source_pmcid": "PMC12127322" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "GALNT2 catalyzes O-glycosylation, impacting T cell exhaustion.", "mechanism": "Marker gene for exhausted CD8+ T cells; predictive for LUAD prognosis.", "protein": "GALNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spect", "gene_name": "GALNT2", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q10471" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "HEG1 is a cell surface glycoprotein, likely modulating cell adhesion.", "mechanism": "Part of a three-gene signature predicting prognosis and immunotherapy response.", "protein": "HEG1", "protein_enriched": { "function": "Synaptic adhesion molecule required for the formation of target-specific synapses. Required for formation of target-specific synapses at hippocampal mossy fiber synapses. Required for formation of mos", "gene_name": "KIRREL3", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q8IZU9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "SMS is involved in glycan biosynthesis.", "mechanism": "Included in glycosylation-related prognostic gene signature.", "protein": "SMS", "protein_enriched": { "function": "Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM)", "gene_name": "SMS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52788" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (HNSCC)", "glycan_involvement": "MYO1B is membrane-associated and glycosylated.", "mechanism": "Included in glycosylation-related prognostic gene signature.", "protein": "MYO1B", "protein_enriched": { "function": "Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, whi", "gene_name": "MYO16", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6X6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127322" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "HMMR is a hyaluronan receptor glycoprotein, mediating cell motility.", "mechanism": "High expression correlates with poor prognosis; knockdown inhibits proliferation and migration.", "protein": "HMMR", "relationship_type": "biomarker", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "YBX2 is glycosylated, affecting its stability and function.", "mechanism": "Improves diagnostic and therapy options; part of YBXs score for therapy prediction.", "protein": "YBX2", "protein_enriched": { "function": "Major constituent of messenger ribonucleoprotein particles (mRNPs). Involved in the regulation of the stability and/or translation of germ cell mRNAs. Binds to Y-box consensus promoter element. Binds ", "gene_name": "YBX2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2T7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127322" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "ERRFI1 may be glycosylated, influencing immune signaling.", "mechanism": "Key gene in STING pathway; knockdown regulates immune response.", "protein": "ERRFI1", "protein_enriched": { "function": "Acts as a transcriptional transactivator of TCEA1 elongation activity (By similarity). Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. Potent inducer of apoptosis in pr", "gene_name": "EAF2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96CJ1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127322" }, { "confidence": "high", "disease": "Central obesity", "glycan_involvement": "ApoB is N-glycosylated, affecting its stability and function in lipid transport.", "mechanism": "Lutein supplementation reduces plasma ApoB levels, improving lipid profile.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Central obesity", "glycan_involvement": "AGEs are glycoprotein adducts formed by non-enzymatic glycation.", "mechanism": "Lutein reduces plasma AGEs (CEL, CML, MG-H1), lowering oxidative stress.", "protein": "Advanced glycation end products (AGEs)", "relationship_type": "biomarker", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "MMPs are glycosylated, which affects their secretion and activity.", "mechanism": "Hinokitiol and Coronarin D inhibit MMPs, reducing metastasis.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CDK1 may be glycosylated, influencing cell cycle regulation.", "mechanism": "Auraptene and perillic acid downregulate CDK1, causing cell cycle arrest.", "protein": "CDK1", "protein_enriched": { "function": "Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (Pub", "gene_name": "CDK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06493" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CDK4 may be glycosylated, affecting its stability and activity.", "mechanism": "Carvacrol and perillic acid downregulate CDK4, inhibiting proliferation.", "protein": "CDK4", "protein_enriched": { "function": "Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transi", "gene_name": "CDK4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11802" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Bcl-2 glycosylation may regulate its anti-apoptotic function.", "mechanism": "Thymoquinone and D-limonene downregulate Bcl-2, promoting apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Bax glycosylation may modulate its pro-apoptotic activity.", "mechanism": "Thymoquinone upregulates Bax, activating apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "NF-\u03baB glycosylation can affect nuclear translocation and transcriptional activity.", "mechanism": "Ursolic acid derivatives and artesunate inhibit NF-\u03baB signaling, reducing inflammation and tumor growth.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Chemoresistant cancer", "glycan_involvement": "P-gp is heavily N-glycosylated, which modulates drug efflux activity.", "mechanism": "\u03b2-elemene inhibits P-gp, increasing drug accumulation in resistant cancer cells.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "TRPM8 glycosylation affects channel trafficking and function.", "mechanism": "Menthol induces TRPM8 overexpression, leading to mitochondrial depolarization and cancer cell death.", "protein": "TRPM8", "protein_enriched": { "function": "Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+). Activated by multiple factors, such as temperature, volt", "gene_name": "TRPM8", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q7Z2W7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127327" }, { "confidence": "high", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "HSP90 is glycosylated, which may affect chaperone function and client protein interactions.", "mechanism": "Regulates necroptosis signaling via stabilization of RIPK1/3 and MLKL; inhibition reduces IEC death and inflammation.", "protein": "HSP90 (HSP90AA1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127353" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "ZO-1 is glycosylated; glycosylation may regulate junction assembly.", "mechanism": "Loss of ZO-1 correlates with increased permeability and barrier breakdown in UC.", "protein": "ZO-1 (TJP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12127353" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Occludin is glycosylated; glycosylation affects membrane localization and function.", "mechanism": "Reduced Occludin expression is associated with impaired tight junctions and increased permeability in UC.", "protein": "Occludin (OCLN)", "relationship_type": "biomarker", "source_pmcid": "PMC12127353" }, { "confidence": "high", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "Highly O-glycosylated; glycosylation is essential for mucus gel formation.", "mechanism": "MUC-2 maintains mucus barrier; increased expression protects against bacterial invasion and inflammation.", "protein": "MUC-2", "relationship_type": "protective", "source_pmcid": "PMC12127353" }, { "confidence": "medium", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "EGFR N-glycosylation modulates receptor stability and signaling.", "mechanism": "EGFR is a client of HSP90; its downregulation indicates HSP90 inhibition and reduced inflammatory signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127353" }, { "confidence": "medium", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "HSP70 glycosylation may affect chaperone activity.", "mechanism": "Upregulated upon HSP90 inhibition; indicates cellular stress response and protective adaptation.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127353" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Altered glycosylation may affect HSP90 function in tumorigenesis.", "mechanism": "Chronic inflammation and barrier dysfunction in UC, regulated by HSP90, increase risk of colorectal cancer.", "protein": "HSP90 (HSP90AA1)", "relationship_type": "causal", "source_pmcid": "PMC12127353" }, { "confidence": "medium", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "Glycosylation status may modulate ZO-1 function.", "mechanism": "Restoration of ZO-1 expression improves barrier integrity and reduces inflammation.", "protein": "ZO-1 (TJP1)", "relationship_type": "protective", "source_pmcid": "PMC12127353" }, { "confidence": "medium", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "Glycosylation required for Occludin stability and tight junction formation.", "mechanism": "Increased Occludin expression correlates with improved barrier function and reduced disease severity.", "protein": "Occludin (OCLN)", "relationship_type": "protective", "source_pmcid": "PMC12127353" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation critical for MUC-2 protective function.", "mechanism": "Reduced MUC-2 expression marks goblet cell loss and barrier compromise in UC.", "protein": "MUC-2", "relationship_type": "biomarker", "source_pmcid": "PMC12127353" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "CA-62 recognizes a specific N-glycosylation pattern unique to malignant transformation.", "mechanism": "Elevated CA-62 levels on poorly differentiated epithelial cells enable early detection of NSCLC.", "protein": "CA-62", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "high", "disease": "Squamous cell carcinoma (lung)", "glycan_involvement": "N-glycosylation pattern on cell surface is targeted by CA-62.", "mechanism": "CA-62 is highly expressed in squamous cell carcinoma, aiding early diagnosis.", "protein": "CA-62", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "high", "disease": "Adenocarcinoma (lung)", "glycan_involvement": "N-glycosylation epitope is present on poorly differentiated adenocarcinoma cells.", "mechanism": "CA-62 is elevated in lung adenocarcinoma, especially at early stages.", "protein": "CA-62", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation affects CEA's stability and detection.", "mechanism": "CEA is moderately elevated in NSCLC, used for diagnosis and monitoring.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (lung)", "glycan_involvement": "Fragment of cytokeratin 19, glycosylation may affect release into serum.", "mechanism": "CYFRA 21-1 is a marker for squamous cell carcinoma subtype of NSCLC.", "protein": "CYFRA 21-1", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "low", "disease": "Adenocarcinoma (lung)", "glycan_involvement": "O-glycosylation on mucin-type glycoprotein.", "mechanism": "CA-125 is sometimes elevated in lung adenocarcinoma.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "low", "disease": "Adenocarcinoma (lung)", "glycan_involvement": "O-glycosylation on mucin-type glycoprotein.", "mechanism": "CA 15-3 may be elevated in lung adenocarcinoma.", "protein": "CA 15-3", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "low", "disease": "Large cell lung cancer", "glycan_involvement": "Sialylated glycan epitope on mucins.", "mechanism": "CA 19-9 is occasionally elevated in large cell lung cancer.", "protein": "CA 19-9", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:17502375, PubMed:22932902). Mediates transport of beta-alanine (PubMed:17502375). Can also mediate transport", "gene_name": "SLC6A13", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NSD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (lung)", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "SCC antigen is used for squamous cell carcinoma diagnosis.", "protein": "SCC", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "high", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Absence of malignant N-glycosylation pattern in COPD.", "mechanism": "CA-62 levels remain low in COPD, supporting its specificity for cancer.", "protein": "CA-62", "relationship_type": "biomarker", "source_pmcid": "PMC12127355" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Sialylation and glycosylation near catalytic entrance modulate substrate specificity and leukocyte binding.", "mechanism": "VAP-1 mediates leukocyte adhesion, produces toxic metabolites (formaldehyde, MGO, H2O2) causing endothelial injury, oxidative stress, and AGE formation, accelerating plaque formation.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Glycosylation affects adhesion function and substrate specificity.", "mechanism": "Elevated plasma VAP-1 correlates with CHD severity and adverse events; inhibition reduces plaque size and stabilizes plaques.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation influences enzymatic activity and substrate access.", "mechanism": "High SSAO/VAP-1 activity increases toxic metabolites, oxidative stress, and AGEs, contributing to diabetes onset and vascular complications.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation maintains protein stability and function.", "mechanism": "Elevated plasma VAP-1/SSAO activity predicts HF severity and mortality; contributes to endothelial injury via oxidative stress.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127361" }, { "confidence": "medium", "disease": "Essential hypertension", "glycan_involvement": "Sialylation required for adhesion molecule activity.", "mechanism": "VAP-1 promotes vascular inflammation and remodeling; inhibition reduces inflammatory mediators and may slow hypertension progression.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects localization and activity in adipocytes.", "mechanism": "VAP-1 regulates glucose uptake in adipocytes, influences adipogenesis and fat deposition; SSAO activity linked to low-grade inflammation in obesity.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation modulates enzymatic activity relevant to renal injury.", "mechanism": "Elevated VAP-1/SSAO activity correlates with albuminuria and ESRD risk; inhibition reduces renal damage.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Diabetic retinopathy", "glycan_involvement": "Glycosylation affects vascular adhesion and enzymatic function.", "mechanism": "VAP-1 levels correlate with VEGF and retinal vascular permeability; inhibition reduces retinal thickening and permeability.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12127361" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation influences circulating sVAP-1 levels.", "mechanism": "Elevated sVAP-1 in NAFLD patients links liver inflammation to increased CVD risk.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127361" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation required for adhesion and enzymatic activity.", "mechanism": "High sVAP-1 levels associated with increased risk of stroke and adverse cardiovascular events.", "protein": "Vascular adhesion protein-1 (VAP-1)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia (PubMed:19588076, PubMed:24304424, PubMed:9653080)", "gene_name": "AOC3", "glycan_count": 47, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G06110VR", "G17208MA", "G22573RC", "G22768VO", "G39188ZX", "G87661QW", "G90659AW", "G43417UB", "G02030ZB", "G04657PL", "G12341GU", "G27058EU", "G41071NU", "G42466VF", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G57776ZS", "G64409MC", "G68490OW", "G69521XL", "G70232NH", "G80075MS", "G81263BG", "G82463GQ", "G84452RH", "G91636VS", "G05962QB", "G07246CJ", "G10819WX", "G24528MX", "G29299MO", "G29545VG", "G37818NZ", "G40834TG", "G40926MX", "G53075ES", "G55132BD", "G66163OV", "G79666IR", "G80479JV", "G80669SJ", "G81637OR", "G82443XX", "G87123QX", "G90382BL" ], "uniprot_id": "Q16853" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127361" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation modulates ITG-\u03b26 stability and cell adhesion.", "mechanism": "Quercetin downregulates ITG-\u03b26, inhibiting EMT and metastasis.", "protein": "Integrin-\u03b26 (ITG-\u03b26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation required for VEGF-A secretion and function.", "mechanism": "Quercetin suppresses VEGF-A expression, inhibiting angiogenesis.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation essential for VEGFR-2 cell surface localization.", "mechanism": "Quercetin downregulates VEGFR-2, blocking angiogenic signaling.", "protein": "VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation affects uPA secretion and activity.", "mechanism": "Quercetin reduces uPA activity, limiting invasion and metastasis.", "protein": "uPA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation required for uPAR function and localization.", "mechanism": "Quercetin decreases uPAR expression, inhibiting cell migration.", "protein": "uPAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation modulates P-gp trafficking and drug efflux.", "mechanism": "Quercetin downregulates P-gp, reversing multidrug resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "medium", "disease": "Gastric cancer-associated inflammation", "glycan_involvement": "Glycosylation required for LCN2 secretion.", "mechanism": "Quercetin inhibits SP1/LCN2 axis, reducing inflammation and apoptosis.", "protein": "LCN2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation affects MMP-2 secretion and activation.", "mechanism": "Quercetin inhibits MMP-2 activity, blocking invasion.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation required for MMP-9 secretion.", "mechanism": "Quercetin suppresses MMP-9, reducing metastasis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127391" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Potential glycosylation may affect GSDMD activation (not specified).", "mechanism": "Quercetin upregulates GSDMD, inducing pyroptosis.", "protein": "Gasdermin D (GSDMD)", "protein_enriched": { "function": "Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27281216). This form constitutes the p", "gene_name": "GSDMD", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P57764" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127391" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation affects albumin stability and clearance.", "mechanism": "Decreased serum albumin indicates impaired hepatic synthesis due to heavy metal toxicity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "high", "disease": "Immunodeficiency", "glycan_involvement": "N-glycosylation critical for IgM structure and function.", "mechanism": "Reduced IgM levels reflect compromised humoral immunity in exposed workers.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation modulates ALP activity and secretion.", "mechanism": "Elevated ALP signals cholestatic or hepatocellular injury from heavy metals.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects ALT stability.", "mechanism": "Increased ALT is a marker of hepatocellular damage.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation influences AST half-life.", "mechanism": "Elevated AST indicates liver cell injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Albumin glycosylation affects bilirubin binding and transport.", "mechanism": "Increased total bilirubin reflects impaired hepatic clearance.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Serum glycoprotein composition altered in disease.", "mechanism": "Decreased total protein suggests reduced hepatic synthetic function.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation of apolipoprotein B affects LDL metabolism.", "mechanism": "Elevated LDL is associated with increased cardiovascular risk in exposed workers.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of apolipoprotein A-I modulates HDL function.", "mechanism": "Decreased HDL is linked to higher cardiovascular risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation regulates platelet function and clearance.", "mechanism": "Increased platelet count and altered glycoprotein expression reflect hematologic stress.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12127436" }, { "confidence": "high", "disease": "Type II diabetes mellitus (T2DM)", "glycan_involvement": "PPAR\u03b3 is N-glycosylated, which may affect receptor stability and function.", "mechanism": "PPAR\u03b3 activation improves insulin sensitivity and glucose homeostasis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "N-glycosylation may modulate receptor activity in hepatic tissue.", "mechanism": "PPAR\u03b3 agonists (e.g., pioglitazone) are approved for NASH treatment due to their metabolic effects.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Polycystic ovarian syndrome (PCOS)", "glycan_involvement": "Glycosylation may influence receptor signaling in reproductive tissues.", "mechanism": "PPAR\u03b3 agonists decrease androgen levels, enhance ovulation, and improve glucose tolerance.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation status may affect receptor turnover and susceptibility to toxic metabolites.", "mechanism": "Full agonists of PPAR\u03b3 (e.g., troglitazone) can cause liver toxicity via reactive metabolite formation.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127462" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "Altered glycosylation may affect receptor-mediated cell proliferation.", "mechanism": "Long-term use of PPAR\u03b3 agonists (e.g., pioglitazone) is associated with increased bladder cancer risk.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Type II diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation of P-gp is essential for its trafficking and function.", "mechanism": "Compound 7 is not a P-gp substrate, potentially improving oral bioavailability for antidiabetic therapy.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12127462" }, { "confidence": "high", "disease": "Type II diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect receptor expression and detection.", "mechanism": "PPAR\u03b3 gene expression in pancreatic tissue is downregulated in diabetes and restored by therapy.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation may modulate receptor response to different ligands.", "mechanism": "Selective PPAR\u03b3 modulators (SPPARMs, e.g., compound 7) show reduced hepatotoxicity compared to full agonists.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12127462" }, { "confidence": "medium", "disease": "Type II diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation may influence partial vs. full agonist signaling.", "mechanism": "Partial activation of PPAR\u03b3 by SPPARMs improves insulin sensitivity with fewer side effects.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12127462" }, { "confidence": "high", "disease": "Type II diabetes mellitus (T2DM)", "glycan_involvement": "N-glycosylation may affect receptor stability and ligand responsiveness.", "mechanism": "Compound 7 increases PPAR\u03b3 expression and activity, lowering blood glucose and protecting pancreatic tissue.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12127462" }, { "confidence": "high", "disease": "Tuberculosis (TB)", "glycan_involvement": "Mono- and digalactosylated Fc-glycans negatively associated with phagocytic capacity.", "mechanism": "Enhanced Fc-mediated phagocytosis of mycobacteria via FcR interactions contributes to mycobacterial growth control.", "protein": "IgG Fc region", "relationship_type": "protective", "source_pmcid": "PMC12127566" }, { "confidence": "high", "disease": "Active TB disease", "glycan_involvement": "Digalactosylation of Fc region is key for biomarker function.", "mechanism": "PPD-specific digalactosylated IgG discriminates between TB disease and TB infection.", "protein": "PPD-specific digalactosylated IgG", "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Active TB disease", "glycan_involvement": "Not specified.", "mechanism": "Increased IgG4 levels in active TB compared to latent infection and treated TB.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Active TB disease", "glycan_involvement": "Not specified.", "mechanism": "Fc\u03b3RI RNA levels can discriminate active TB from latent infection.", "protein": "Fc\u03b3RI (CD64)", "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Latent TB infection (TBI)", "glycan_involvement": "Affinity may be modulated by Fc glycosylation.", "mechanism": "Higher affinity of PPD-specific IgG for Fc\u03b3RIIIa associated with enhanced antimicrobial functions.", "protein": "Fc\u03b3RIIIa", "relationship_type": "protective", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Tuberculosis (TB)", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "LAM-specific antibodies enhance Fc\u03b3R-mediated phagocytosis and reduce intracellular mycobacterial growth.", "protein": "Lipoarabinomannan (LAM)-specific antibody", "relationship_type": "protective", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Latent TB infection (TBI)", "glycan_involvement": "Fucosylation of Fc region impacts disease risk.", "mechanism": "Increased IgG fucosylation in TBI at risk to progress to TB disease.", "protein": "IgG Fc region (fucosylation)", "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "medium", "disease": "Tuberculosis (TB)", "glycan_involvement": "Absence of fucosylation increases FcR binding.", "mechanism": "Non-fucosylated IgG-Fc structures strongly interact with FcRs and may compete with antigen-specific antibodies, correlating with lack of growth control.", "protein": "Total IgG-Fc (non-fucosylated)", "relationship_type": "causal", "source_pmcid": "PMC12127566" }, { "confidence": "low", "disease": "Chronic hepatitis B", "glycan_involvement": "Not specified.", "mechanism": "Decreased Fc\u03b3RIIb expression in liver correlates with disease severity.", "protein": "Fc\u03b3RIIb", "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "low", "disease": "Latent TB infection (TBI)", "glycan_involvement": "Not specified.", "mechanism": "Elevated Fc\u03b3RIIIa levels in TBI compared to uninfected controls.", "protein": "Fc\u03b3RIIIa", "relationship_type": "biomarker", "source_pmcid": "PMC12127566" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Tragacanthin's glycan-rich structure enables complex formation and oil entrapment.", "mechanism": "Used as a fat replacer to reduce saturated and trans fatty acids, lowering risk factors for cardiovascular disease.", "protein": "Gelatin\u2013tragacanthin complex", "relationship_type": "protective", "source_pmcid": "PMC12127619" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycan-mediated crosslinking (via Ca2+ ion bridges) enhances gel stability.", "mechanism": "Oleogels mimic fat texture, enabling reduction of caloric fat intake in foods.", "protein": "Gelatin\u2013tragacanthin\u2013Ca2+ complex", "relationship_type": "protective", "source_pmcid": "PMC12127619" }, { "confidence": "medium", "disease": "Trans fatty acid-induced disorders", "glycan_involvement": "Gelatin's glycosylation enables amphiphilic interactions for oil entrapment.", "mechanism": "Replacement of traditional fats with gelatin-based oleogels reduces dietary trans fats.", "protein": "Gelatin", "relationship_type": "protective", "source_pmcid": "PMC12127619" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "High galacturonic acid content (glycan) enables electrostatic interactions.", "mechanism": "Tragacanthin increases viscosity and stability of oleogels, supporting fat replacement.", "protein": "Tragacanthin", "relationship_type": "protective", "source_pmcid": "PMC12127619" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Ca2+ bridges between glycan carboxyl groups stabilize the network.", "mechanism": "Ca2+-induced ion bridges create heat-stable oleogels, facilitating healthier fat alternatives.", "protein": "Gelatin\u2013tragacanthin\u2013Ca2+ complex", "relationship_type": "protective", "source_pmcid": "PMC12127619" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Decreased serum albumin indicates impaired liver synthetic function after CPB.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may affect renal handling and filtration.", "mechanism": "Hypoalbuminemia reflects increased renal excretion and glomerular permeability post-CPB.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "ALKP is heavily glycosylated; glycan structure modulates activity and clearance.", "mechanism": "Elevated ALKP post-CPB indicates cholestatic liver injury.", "protein": "Alkaline phosphatase (ALKP)", "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "AST is glycosylated; glycosylation may affect release and stability.", "mechanism": "Increased AST reflects hepatocyte and sinusoidal cell damage during CPB.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "high", "disease": "Postoperative mortality", "glycan_involvement": "Glycosylation may influence serum half-life and detection.", "mechanism": "Significantly elevated AST post-surgery is associated with increased risk of death.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "predictive biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "ALT is glycosylated; glycan status may affect release.", "mechanism": "Elevated ALT post-CPB indicates hepatocellular injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "medium", "disease": "Hypoalbuminemia", "glycan_involvement": "Includes multiple glycoproteins; glycosylation affects serum protein stability.", "mechanism": "Decreased total protein post-CPB reflects impaired hepatic synthesis and/or renal loss.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Transported bound to albumin (glycoprotein).", "mechanism": "Decreased indirect bilirubin post-CPB may reflect altered hepatic clearance.", "protein": "Indirect bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "medium", "disease": "Bleeding", "glycan_involvement": "N-glycosylation critical for secretion and function.", "mechanism": "Reduced synthesis of glycosylated coagulation factors post-CPB increases bleeding risk.", "protein": "Coagulation factors", "relationship_type": "causal", "source_pmcid": "PMC12127762" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "GGT is glycosylated; glycan structure affects activity.", "mechanism": "Elevated GGT post-CPB indicates cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127762" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Promotes hepatic stellate cell activation and ECM production via Smad2/3 signaling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Smad2 is glycosylated, which may affect stability and signaling.", "mechanism": "Transduces TGF-\u03b21 signals to nucleus, promoting fibrogenic gene expression.", "protein": "Smad2", "relationship_type": "causal", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Smad3 glycosylation may modulate nuclear translocation.", "mechanism": "Mediates TGF-\u03b21-induced transcription of profibrotic genes.", "protein": "Smad3", "protein_enriched": { "function": "Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194).", "gene_name": "SMAD5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99717" }, "relationship_type": "causal", "source_pmcid": "PMC12127870" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Smad7 is glycosylated; glycosylation may affect inhibitory function.", "mechanism": "Inhibits TGF-\u03b21/Smad2/3 signaling, reducing fibrosis.", "protein": "Smad7", "relationship_type": "protective", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Nrf2 is glycosylated; glycosylation may regulate nuclear localization.", "mechanism": "Activates antioxidant response (HO-1, NQO-1), suppressing oxidative stress and inflammation.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12127870" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "HO-1 is glycosylated, which may affect enzymatic activity.", "mechanism": "Antioxidant enzyme induced by Nrf2, reduces oxidative damage.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12127870" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "NQO-1 is glycosylated; glycosylation may affect stability.", "mechanism": "Detoxification enzyme induced by Nrf2, reduces ROS and inflammation.", "protein": "NQO-1", "relationship_type": "protective", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen I is highly glycosylated (O-glycosylation), essential for fibril formation.", "mechanism": "Major ECM component deposited during fibrosis.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen III is glycosylated, affecting ECM assembly.", "mechanism": "ECM protein upregulated in fibrotic liver.", "protein": "Collagen III", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A2", "glycan_count": 18, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G25637MV", "G27915IV", "G31852PQ", "G39188ZX", "G40574BA", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G43417UB", "G49108TO" ], "uniprot_id": "P08123" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12127870" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "\u03b1-SMA is glycosylated; glycosylation may affect filament assembly.", "mechanism": "Marker of activated hepatic stellate cells (myofibroblasts) in fibrosis.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12127870" }, { "confidence": "high", "disease": "Opioid dependence", "glycan_involvement": "sTREM2 is N-glycosylated; glycosylation affects shedding and function.", "mechanism": "Elevated CSF sTREM2 indicates microglial activation and neuroimmune response in opioid dependence.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "high", "disease": "Opioid dependence", "glycan_involvement": "YKL-40 is a secreted glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "Elevated (after normalization) YKL-40 reflects astrocyte activation and neuroinflammation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "IL-8 is O-glycosylated; glycosylation modulates secretion and receptor interaction.", "mechanism": "Increased IL-8 (after normalization) indicates microglial/endothelial activation and CNS inflammation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "TYRO3 is N-glycosylated; glycosylation required for cell surface expression.", "mechanism": "Elevated TYRO3 (after normalization) suggests compensatory anti-inflammatory signaling in CNS.", "protein": "TYRO3", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes includin", "gene_name": "TYRO3", "glycan_count": 13, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G80920RR", "G06356OH", "G15169WU", "G16125XL", "G48414YA", "G57888GL", "G00273SJ", "G22310AV", "G99668VU", "G37881RL", "G52527GH", "G62765YT", "G84452RH" ], "uniprot_id": "Q06418" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated NfL indicates axonal injury/neuronal damage in opioid dependence.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "Tau can be O-glycosylated; glycosylation may affect aggregation.", "mechanism": "Increased P-Tau (after normalization) suggests tau hyperphosphorylation and possible neurodegeneration.", "protein": "P-Tau", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Opioid dependence", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation affects processing to A\u03b2 peptides.", "mechanism": "Reduced A\u03b242/A\u03b240 ratio indicates altered amyloid metabolism, possibly linked to microglial activation.", "protein": "A\u03b242/A\u03b240", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates sTREM2 function.", "mechanism": "Elevated sTREM2 is associated with microglial activation in Alzheimer's disease.", "protein": "sTREM2", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "YKL-40 is elevated in MS, reflecting astrocyte/microglial activation.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "low", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "GAS6 is N-glycosylated; glycosylation affects receptor binding.", "mechanism": "GAS6/AXL signaling regulates BBB permeability; altered levels may reflect BBB changes in neuroinflammation.", "protein": "GAS6", "relationship_type": "biomarker", "source_pmcid": "PMC12127996" }, { "confidence": "high", "disease": "Severe MPP", "glycan_involvement": "Glycosylation required for pathogen binding and immune signaling.", "mechanism": "Upregulated in severe MPP; mediates pathogen recognition and immune activation via C-type lectin binding.", "protein": "CD209", "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Catalyzes core 1 O-glycan synthesis, impacting mucosal immunity.", "mechanism": "Downregulated in severe MPP; regulates O-glycosylation of mucins and immune proteins.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Essential for O-glycosylation of mucins and immune proteins.", "mechanism": "Downregulated in severe MPP; chaperones C1GALT1 for proper O-glycosylation.", "protein": "C1GALT1C1", "protein_enriched": { "function": "Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance. Associates with the striatin-interacting ", "gene_name": "CTTNBP2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8WZ74" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Glycosylation modulates stability and immune function.", "mechanism": "Upregulated in severe MPP; involved in inflammatory response and tissue remodeling.", "protein": "CHI3L2", "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Glycosylation may affect membrane localization and trafficking.", "mechanism": "Downregulated in severe MPP; regulates vesicle trafficking and membrane recycling.", "protein": "SCAMP1", "protein_enriched": { "function": "Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface", "gene_name": "SCAMP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "O15126" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Potential glycosylation affects vesicle targeting.", "mechanism": "Downregulated in severe MPP; involved in Rab protein recruitment for vesicle trafficking.", "protein": "CHM", "protein_enriched": { "function": "Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B composed of RABGGTA and", "gene_name": "CHM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24386" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Downregulated in severe MPP; regulates chromatin remodeling and interferon signaling.", "protein": "PBRM1", "protein_enriched": { "function": "Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling co", "gene_name": "PBRM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U86" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "medium", "disease": "Severe MPP", "glycan_involvement": "Glycosylation modulates chemokine activity and receptor binding.", "mechanism": "Upregulated in severe MPP; chemokine involved in neutrophil recruitment and inflammation.", "protein": "CXCL5", "protein_enriched": { "function": "Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes", "gene_name": "CXCL5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128088" }, { "confidence": "low", "disease": "Asthma (complication)", "glycan_involvement": "Glycosylation critical for allergen/pathogen recognition.", "mechanism": "CD209-mediated immune activation may contribute to asthma development post-MPP.", "protein": "CD209", "relationship_type": "causal", "source_pmcid": "PMC12128088" }, { "confidence": "low", "disease": "Pneumonitis (complication)", "glycan_involvement": "Defective O-glycosylation reduces mucin protection.", "mechanism": "Altered O-glycosylation may impair mucosal barrier, increasing risk of pneumonitis.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC12128088" }, { "confidence": "high", "disease": "Arteriovenous fistula failure", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and inflammatory signaling.", "mechanism": "Elevated CRP reflects chronic inflammation, which promotes vascular remodeling and AVF failure.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128127" }, { "confidence": "high", "disease": "Arteriovenous fistula failure", "glycan_involvement": "Albumin glycosylation may modulate toxin binding and endothelial interactions.", "mechanism": "Albumin binds uremic toxins and forms complexes that activate endothelial cells, induce inflammation, and disrupt endothelial glycocalyx, promoting AVF failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Arteriovenous fistula failure", "glycan_involvement": "Ferritin glycosylation may affect its stability and iron storage function.", "mechanism": "Higher ferritin levels indicate better iron stores and nutritional status, supporting vascular health and AVF patency.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "protective", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Arteriovenous fistula failure", "glycan_involvement": "Transferrin glycosylation affects iron binding and receptor interactions.", "mechanism": "Transferrin levels reflect iron transport and nutritional status, influencing vascular health.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "PTH glycosylation modulates hormone stability and receptor binding.", "mechanism": "Elevated PTH promotes vascular smooth muscle cell transformation and vessel wall thickening, contributing to AVF failure.", "protein": "Parathyroid hormone", "relationship_type": "causal", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor interactions.", "mechanism": "TNF-\u03b1 released from activated monocytes/endothelial cells induces vessel wall inflammation and remodeling.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "IL-6 glycosylation influences stability and signaling.", "mechanism": "IL-6 stimulates CRP synthesis and promotes systemic inflammation, contributing to AVF failure.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may affect albumin\u2019s interaction with coagulation factors.", "mechanism": "Low albumin impairs endothelial repair, exposes subendothelial tissue, and activates coagulation, increasing thrombosis risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP is associated with increased risk of vascular thrombosis due to inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128127" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation may affect albumin\u2019s binding to toxins and CPP formation.", "mechanism": "Albumin-toxin complexes facilitate calprotectin particle formation, accelerating vascular calcification.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12128127" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "CD248 is a glycoprotein; glycosylation may affect its cell surface localization and function.", "mechanism": "Promotes mesangial angiogenesis and interstitial eosinophilic infiltration via upregulation of VEGFC and CCL-5.", "protein": "CD248", "relationship_type": "causal", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "VEGFC is glycosylated, which is important for its secretion and receptor binding.", "mechanism": "VEGFC mediates neovascularization in the glomerular mesangial area, downstream of CD248.", "protein": "VEGFC", "relationship_type": "causal", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "CCL-5 glycosylation may influence chemokine activity and cell recruitment.", "mechanism": "CCL-5 promotes eosinophilic infiltration in the renal interstitium, downstream of CD248.", "protein": "CCL-5", "relationship_type": "causal", "source_pmcid": "PMC12128132" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Glycosylation may regulate CD248's role in tumor angiogenesis.", "mechanism": "CD248 overexpression in vasculature predicts adverse clinical outcomes.", "protein": "CD248", "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "medium", "disease": "IgA nephropathy", "glycan_involvement": "Glycosylation may affect CD248's function in mesangial cells.", "mechanism": "CD248 expression increases in later stages and predicts renal survival.", "protein": "CD248", "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "CD31 glycosylation is important for endothelial cell adhesion.", "mechanism": "CD31 marks neovascularization in mesangial regions of DN.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "CD3 glycosylation may affect T cell activation and migration.", "mechanism": "CD3-positive T cell infiltration correlates with eosinophilic infiltration and CCL-5 expression.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Targeting glycosylation may modulate CD248 function.", "mechanism": "CD248 knockdown reduces VEGFC and CCL-5 expression, attenuating angiogenesis and eosinophilic infiltration.", "protein": "CD248", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation required for VEGFC activity.", "mechanism": "VEGFC expression correlates with neovascularization in DN.", "protein": "VEGFC", "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may regulate CCL-5 chemotactic function.", "mechanism": "CCL-5 expression correlates with eosinophilic infiltration and T cell presence.", "protein": "CCL-5", "relationship_type": "biomarker", "source_pmcid": "PMC12128132" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CCR2 is a glycoprotein; glycosylation may affect receptor stability and ligand binding.", "mechanism": "CCR2 mediates monocyte/macrophage recruitment to inflamed tissue via CCL2 binding; targeting CCR2 reduces renal inflammation and SLE progression.", "protein": "CCR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128239" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CCL2 is glycosylated, which may influence secretion and receptor interaction.", "mechanism": "CCL2 is upregulated in SLE kidneys, driving monocyte recruitment and M1 macrophage polarization, exacerbating inflammation.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "causal", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CD86 glycosylation affects surface expression and immune synapse formation.", "mechanism": "CD86 is elevated on M1 macrophages in SLE, correlating with disease severity and pro-inflammatory state.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CD163 glycosylation modulates receptor function and clearance of hemoglobin-haptoglobin complexes.", "mechanism": "CD163 is reduced in SLE, reflecting impaired M2 anti-inflammatory macrophage polarization.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Lupus nephritis (LN)", "glycan_involvement": "CD68 is a heavily glycosylated lysosomal protein; glycosylation affects stability.", "mechanism": "Increased CD68+ macrophages in renal tissue predict LN severity and renal outcomes.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CD47 glycosylation is critical for its 'don't eat me' signal.", "mechanism": "CD47 on macrophage membranes of nanoparticles reduces phagocytic clearance, enhancing immune evasion of therapeutic carriers.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "protective", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CD55 is a glycoprotein; glycosylation is important for complement regulatory function.", "mechanism": "CD55 on nanoparticles inhibits complement activation, reducing immune clearance.", "protein": "CD55", "protein_enriched": { "function": "Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI)", "gene_name": "DDT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P30046" }, "relationship_type": "protective", "source_pmcid": "PMC12128239" }, { "confidence": "high", "disease": "Lupus nephritis (LN)", "glycan_involvement": "IgG Fc glycosylation modulates immune complex formation and effector function.", "mechanism": "IgG immune complex deposition in kidneys drives LN pathology.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is glycosylated; glycosylation affects complement activation.", "mechanism": "C3 depletion is a marker of active SLE and renal involvement.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IL-6 is glycosylated, which may affect secretion and receptor interaction.", "mechanism": "Elevated IL-6 reflects ongoing inflammation in SLE.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128239" }, { "confidence": "high", "disease": "Metabolic Inflammatory Syndrome (MIS)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP reflects chronic low-grade inflammation central to MIS pathogenesis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Metabolic Inflammatory Syndrome (MIS)", "glycan_involvement": "IL-6 is glycosylated, which modulates its secretion and receptor binding.", "mechanism": "IL-6 is upregulated in MIS, driving systemic inflammation and metabolic dysregulation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation but relevant to glycoprotein status.", "mechanism": "HbA1c reflects long-term glycemic control and is elevated in T2DM.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation influences CRP's interaction with immune cells.", "mechanism": "High CRP levels predict increased CVD risk due to persistent inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation modulates IL-6 activity and stability.", "mechanism": "IL-6 promotes vascular inflammation and atherogenesis.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation affects CRP's half-life and immune function.", "mechanism": "Elevated CRP is independently associated with increased risk of death.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Glycosylation impacts IL-6's receptor interactions.", "mechanism": "High IL-6 levels are linked to increased mortality via systemic inflammation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Cardiovascular Mortality", "glycan_involvement": "Reflects glycation status; not classical glycosylation.", "mechanism": "Elevated HbA1c is associated with higher cardiovascular mortality in T2DM and MIS.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "medium", "disease": "Non-alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in NAFLD, indicating hepatic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects IL-6's bioactivity.", "mechanism": "IL-6 is increased in obesity, contributing to systemic inflammation and metabolic complications.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12128253" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "Anti-VCA IgA antibodies are highly sensitive and specific for early NPC detection.", "protein": "EBV Viral Capsid Antigen (VCA)", "protein_enriched": { "function": "Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moieties of the host cell surface proteoglycans. Involved in fusion o", "gene_name": "gB", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P03188" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "IgA against EBNA1 distinguishes NPC cases from controls up to 4 years before diagnosis.", "protein": "EBV Nuclear Antigen 1 (EBNA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "Elevated PD-L1 expression correlates with prognosis and response to immune checkpoint therapy in EBV-associated gastric cancer.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Plasma MIC-1 levels are elevated in NPC and complement EBV DNA/IgA detection.", "protein": "MIC-1 (GDF15)", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "Potential O-glycosylation modulates protein interactions.", "mechanism": "Elevated in CSF of HSV-1 encephalitis patients; indicates neuronal injury.", "protein": "14-3-3 family proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "N-glycosylation influences immune signaling.", "mechanism": "Upregulated in CSF during HSV-1 encephalitis; reflects ER stress and immune activation.", "protein": "Calreticulin", "protein_enriched": { "function": "", "gene_name": "CALR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7P0T861" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Elevated in CSF of HSE patients; marker of CNS inflammation.", "protein": "CXCL8 (IL-8)", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Herpes simplex keratitis", "glycan_involvement": "Glycosylation affects cytokine secretion.", "mechanism": "Upregulated in tears of HSK patients; indicates local inflammation.", "protein": "IL1A", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Herpes simplex keratitis", "glycan_involvement": "Glycosylation may affect peptide stability.", "mechanism": "Elevated in tears of HSK patients; antimicrobial and immune modulator.", "protein": "CAMP (LL-37)", "relationship_type": "biomarker", "source_pmcid": "PMC12128367" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "PD-1 expression in tumor-infiltrating lymphocytes predicts response to immune checkpoint blockade in EBVaGC.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12128367" }, { "confidence": "high", "disease": "Healthcare-associated infection (HAI)", "glycan_involvement": "Outer membrane glycoproteins mediate adhesion and immune evasion.", "mechanism": "K. pneumoniae is a predominant pathogen causing HAIs, especially in lower respiratory tract, bloodstream, and urinary tract.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Healthcare-associated infection (HAI)", "glycan_involvement": "Glycoproteins facilitate colonization and resistance to host defenses.", "mechanism": "E. coli is a frequent cause of HAIs, particularly in urinary tract and bloodstream.", "protein": "Escherichia coli outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Healthcare-associated infection (HAI)", "glycan_involvement": "Glycosylated surface proteins contribute to antibiotic resistance and persistence.", "mechanism": "A. baumannii is a major cause of multidrug-resistant HAIs.", "protein": "Acinetobacter baumannii outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "medium", "disease": "Multidrug-resistant infection", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "ESBLs confer resistance to \u03b2-lactam antibiotics in K. pneumoniae and E. coli.", "protein": "Extended-Spectrum \u03b2-Lactamases (ESBLs)", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Bloodstream infection", "glycan_involvement": "Capsular polysaccharides (glycans) are critical for serum resistance.", "mechanism": "K. pneumoniae is a leading cause of bloodstream HAIs.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Urinary tract infection", "glycan_involvement": "Fimbrial glycoproteins mediate adhesion to uroepithelium.", "mechanism": "E. coli is the most common cause of HAI-associated UTIs.", "protein": "Escherichia coli outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "medium", "disease": "Lower respiratory tract infection", "glycan_involvement": "Glycosylated proteins enhance biofilm formation and persistence.", "mechanism": "A. baumannii frequently causes ventilator-associated pneumonia.", "protein": "Acinetobacter baumannii outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "medium", "disease": "Multidrug-resistant infection", "glycan_involvement": "Altered glycosylation may affect drug permeability.", "mechanism": "K. pneumoniae shows high resistance to cephalosporins and carbapenems.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Multidrug-resistant infection", "glycan_involvement": "Surface glycoproteins contribute to resistance mechanisms.", "mechanism": "A. baumannii is resistant to most antibiotics except tigecycline and polymyxin.", "protein": "Acinetobacter baumannii outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Lower respiratory tract infection", "glycan_involvement": "Capsular polysaccharide (glycan) is a key virulence factor.", "mechanism": "K. pneumoniae is a major cause of HAI-associated pneumonia.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12128370" }, { "confidence": "high", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "Glycosylation affects fibrinogen stability and function in coagulation.", "mechanism": "Lower plasma fibrinogen levels increase NEC risk in neonates, especially with PDA.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Patent ductus arteriosus (PDA)", "glycan_involvement": "Glycosylation modulates fibronectin's role in vascular remodeling.", "mechanism": "Increased fibronectin levels may heighten risk of PDA persistence.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12128525" }, { "confidence": "high", "disease": "Hypercoagulability", "glycan_involvement": "Glycosylation influences fibrinogen's interaction with platelets.", "mechanism": "Decreased fibrinogen and shortened APTT indicate platelet activation and hypercoagulability in PDA neonates.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects fibrinogen's immune functions.", "mechanism": "Lower fibrinogen levels correlate with increased sepsis risk in NEC with PDA.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Necrotizing enterocolitis (NEC)", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP levels reflect inflammation severity in NEC, especially with PDA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Valve glycoprotein glycosylation affects structural integrity.", "mechanism": "Moderate to severe tricuspid regurgitation (glycoprotein dysfunction) is more frequent in PDA, leading to heart failure.", "protein": "Tricuspid valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Intraventricular hemorrhage (IVH)", "glycan_involvement": "Glycosylation impacts fibrinogen's role in vascular stability.", "mechanism": "Lower fibrinogen levels in PDA neonates increase IVH risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12128525" }, { "confidence": "low", "disease": "Periventricular leukomalacia (PVL)", "glycan_involvement": "Glycosylation regulates fibronectin's neurovascular interactions.", "mechanism": "Altered fibronectin may contribute to cerebral vascular remodeling and PVL in PDA neonates.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12128525" }, { "confidence": "low", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects mitral valve structure and function.", "mechanism": "Mitral regurgitation (glycoprotein dysfunction) is observed in PDA neonates, contributing to heart failure.", "protein": "Mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12128525" }, { "confidence": "medium", "disease": "Patent ductus arteriosus (PDA)", "glycan_involvement": "Glycosylation may influence fibrinogen's vascular effects.", "mechanism": "Higher fibrinogen levels are associated with spontaneous PDA closure.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "protective", "source_pmcid": "PMC12128525" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "N-glycosylation required for proper folding and ER localization.", "mechanism": "Upregulated during ER stress in MIRI; mediates apoptosis via CHOP pathway; bisacurone downregulates GRP78 to protect myocardium.", "protein": "GRP78", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Upregulated in ER stress/apoptosis during MIRI; bisacurone downregulates CHOP, reducing apoptosis.", "protein": "CHOP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Cardiac hypertrophy", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "ANP mRNA upregulated in hypertrophy and MIRI; bisacurone reduces ANP expression, indicating reduced hypertrophy.", "protein": "ANP", "relationship_type": "biomarker", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation affects secretion and bioactivity.", "mechanism": "BNP mRNA upregulated in heart failure and MIRI; bisacurone reduces BNP expression, indicating improved cardiac function.", "protein": "BNP", "relationship_type": "biomarker", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Acute myocardial infarction (AMI)", "glycan_involvement": "Not glycosylated.", "mechanism": "cTn-I released during myocardial necrosis; bisacurone reduces cTn-I levels, indicating reduced injury.", "protein": "cTn-I", "relationship_type": "biomarker", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "Not glycosylated.", "mechanism": "HO-1 upregulation protects against oxidative stress and apoptosis; bisacurone increases HO-1 expression.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Bcl-2 anti-apoptotic; bisacurone upregulates Bcl-2, reducing apoptosis in MIRI.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Bax pro-apoptotic; upregulated in MIRI; bisacurone downregulates Bax, reducing apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Myocardial ischemia/reperfusion injury (MIRI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Caspase-3 mediates apoptosis; upregulated in MIRI; bisacurone downregulates Caspase-3.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "causal", "source_pmcid": "PMC12128529" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "GRP78 upregulated in heart failure and ER stress; bisacurone downregulates GRP78, suggesting therapeutic potential.", "protein": "GRP78", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12128529" }, { "confidence": "high", "disease": "Familial Partial Lipodystrophy (FPLD2, Dunnigan syndrome)", "glycan_involvement": "Potential impact on glycosylation of nuclear envelope proteins affecting adipocyte function.", "mechanism": "Pathogenic LMNA variants disrupt nuclear envelope integrity, leading to abnormal adipocyte differentiation and lipoatrophy.", "protein": "Lamin A/C (LMNA)", "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "high", "disease": "Familial Partial Lipodystrophy (FPLD3)", "glycan_involvement": "Glycosylation may modulate PPARG activity and adipocyte differentiation.", "mechanism": "PPARG mutations impair adipogenesis, causing partial lipodystrophy and severe metabolic complications.", "protein": "PPARG", "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "Glycosylation affects ApoB stability and lipid transport.", "mechanism": "Elevated ApoB reflects increased atherogenic lipoproteins in FPLD, contributing to hypertriglyceridemia.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12128538" }, { "confidence": "high", "disease": "Familial Partial Lipodystrophy (FPLD)", "glycan_involvement": "Glycosylation required for leptin secretion and receptor binding.", "mechanism": "Low or inappropriately normal leptin levels signal adipose tissue deficiency and drive hyperphagia.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12128538" }, { "confidence": "high", "disease": "Hypertriglyceridemia/Diabetes Mellitus", "glycan_involvement": "Glycosylation essential for adiponectin multimerization and activity.", "mechanism": "Low adiponectin correlates with insulin resistance and dyslipidemia in FPLD.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12128538" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy (FPLD7)", "glycan_involvement": "Glycosylation may affect CAV1 membrane localization and function.", "mechanism": "CAV1 mutations disrupt lipid droplet formation, leading to partial lipodystrophy.", "protein": "Caveolin-1 (CAV1)", "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy (FPLD4)", "glycan_involvement": "Glycosylation may regulate PLIN1 stability and lipid droplet association.", "mechanism": "PLIN1 mutations impair lipid droplet storage, causing limb lipoatrophy.", "protein": "Perilipin-1 (PLIN1)", "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy (FPLD5)", "glycan_involvement": "Glycosylation may influence CIDEC function in lipid droplet dynamics.", "mechanism": "CIDEC mutations disrupt lipid droplet fusion, leading to limb fat loss and insulin resistance.", "protein": "CIDEC", "protein_enriched": { "function": "Lipid transferase specifically expressed in white adipose tissue, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:18334488, PubMed:19843876, PubMed:20049731", "gene_name": "CIDEC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96AQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy (FPLD6)", "glycan_involvement": "Glycosylation may affect LIPE enzymatic activity.", "mechanism": "LIPE mutations cause defective lipolysis, resulting in lipoatrophy and myopathy.", "protein": "Hormone-sensitive lipase (LIPE)", "protein_enriched": { "function": "Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:15716583,", "gene_name": "LIPE", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q05469" }, "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "medium", "disease": "Familial Partial Lipodystrophy with lipomatosis", "glycan_involvement": "Glycosylation may modulate MFN2 mitochondrial localization.", "mechanism": "MFN2 mutations impair mitochondrial fusion, causing limb lipoatrophy and polyneuropathy.", "protein": "Mitofusin-2 (MFN2)", "relationship_type": "causal", "source_pmcid": "PMC12128538" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which modulates its interaction with the viral spike protein.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2, facilitating viral infection.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Spike protein binds to ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Glycosylation affects ACE2 localization and stability in kidney tissue.", "mechanism": "ACE2 is highly expressed in renal proximal tubules; SARS-CoV-2 infection can damage these cells.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "medium", "disease": "Severe renal impairment", "glycan_involvement": "N-glycans on ACE2 modulate susceptibility to viral infection.", "mechanism": "Viral entry via ACE2 in kidney may exacerbate renal impairment.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "low", "disease": "Severe renal impairment", "glycan_involvement": "Glycosylation may affect transporter function and substrate specificity.", "mechanism": "Facilitates uptake of remdesivir metabolite GS-441524, possibly reducing toxicity.", "protein": "Organic anion-transporting polypeptide", "relationship_type": "protective", "source_pmcid": "PMC12128546" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Spike glycosylation modulates immune evasion and cell tropism.", "mechanism": "Spike-mediated infection of renal cells via ACE2 can lead to injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "low", "disease": "Hepatic disorder", "glycan_involvement": "Glycosylation status may affect ACE2 function in hepatocytes.", "mechanism": "ACE2 expression in liver may contribute to hepatic involvement in COVID-19.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12128546" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects VEGF secretion and receptor binding.", "mechanism": "Altered VEGF levels disrupt placental angiogenesis and maternal endothelial integrity.", "protein": "VEGF", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12128778" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation modulates PlGF stability and bioactivity.", "mechanism": "Reduced PlGF impairs placental vascular development.", "protein": "PlGF", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation influences eNOS localization and function.", "mechanism": "Downregulation by miR-155 leads to reduced NO production and vasoconstriction.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation required for MMP-9 secretion and activity.", "mechanism": "Suppressed by miR-183, leading to impaired trophoblast invasion.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation essential for TGF-\u03b2 secretion and receptor interaction.", "mechanism": "Downregulated by miR-181a and miR-18a, affecting trophoblast invasion.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation modulates IL-6 stability and signaling.", "mechanism": "Upregulated by miR-181a, contributing to inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects IL-8 secretion and chemotactic activity.", "mechanism": "Production increased by miR-125b, promoting immune response and impaired placentation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation required for transporter function and localization.", "mechanism": "Targeted by miR-363, leading to altered nutrient transfer.", "protein": "Amino Acid Transporters (SLC family)", "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation may affect arginase stability.", "mechanism": "Increased arginase depletes NO precursor, contributing to hypertension.", "protein": "Arginase", "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation modulates cytokine secretion and immune signaling.", "mechanism": "Shift to Th1 cytokines promotes inflammation and endothelial dysfunction.", "protein": "Th1/Th2 Cytokines", "relationship_type": "causal", "source_pmcid": "PMC12128778" }, { "confidence": "medium", "disease": "Immune Reconstitution Failure", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its clearance and immune interactions.", "mechanism": "Higher LDL-C levels associated with reduced risk of poor immune reconstitution in PLWH.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "protective", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation modulates LDL receptor binding and metabolism.", "mechanism": "Elevated LDL-C is a marker of dyslipidemia post-ART switch.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129012" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL glycosylation influences anti-inflammatory properties.", "mechanism": "HDL-C levels monitored as part of lipid profile in ART-treated PLWH.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12129012" }, { "confidence": "medium", "disease": "Renal Impairment", "glycan_involvement": "Albumin glycosylation affects renal filtration and stability.", "mechanism": "Serum albumin and eGFR used to assess renal function after ART switch.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation enhances drug solubility and bioavailability.", "mechanism": "Emtricitabine is a nucleoside analog used in ART regimens for HIV suppression.", "protein": "Emtricitabine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation enhances drug solubility and bioavailability.", "mechanism": "Lamivudine is a nucleoside analog used in ART regimens for HIV suppression.", "protein": "Lamivudine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "Renal Impairment", "glycan_involvement": "Prodrug glycosylation improves renal targeting and reduces toxicity.", "mechanism": "TAF preferred over TDF for patients with renal impairment due to improved renal safety.", "protein": "Tenofovir Alafenamide", "relationship_type": "protective", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may affect drug pharmacokinetics.", "mechanism": "Bictegravir is an integrase inhibitor used in ART regimens for HIV suppression.", "protein": "Bictegravir", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129012" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Potential indirect effects via glycoprotein-mediated glucose metabolism.", "mechanism": "Switch to DTG/3TC associated with increased incidence of hyperglycemia in PLWH.", "protein": "Dolutegravir", "relationship_type": "causal", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "Immune Reconstitution Failure", "glycan_involvement": "CD4 glycosylation modulates HIV binding and immune signaling.", "mechanism": "CD4+ T cell count used to monitor immune recovery in PLWH.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129012" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "RAGE binds advanced glycation end products (AGEs), which are glycated proteins/lipids.", "mechanism": "RAGE mediates AGE-induced oxidative stress and apoptosis in hepatocytes; downregulation reduces ROS and apoptosis.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129013" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Indirect; BCL2 expression modulated downstream of AGE-RAGE signaling.", "mechanism": "Upregulation of BCL2 inhibits apoptosis in hepatocytes, reducing MAFLD progression.", "protein": "BCL2", "relationship_type": "protective", "source_pmcid": "PMC12129013" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Indirect; apoptosis triggered by AGE-RAGE pathway.", "mechanism": "CASP3 activation promotes hepatocyte apoptosis in MAFLD; inhibition alleviates disease.", "protein": "CASP3", "relationship_type": "causal", "source_pmcid": "PMC12129013" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "AGEs are glycated proteins/lipids; RAGE is a glycoprotein receptor.", "mechanism": "AGE-RAGE signaling contributes to diabetic complications via oxidative stress and inflammation.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "EGFR is a glycoprotein; glycosylation affects ligand binding and signaling.", "mechanism": "EGFR pathway involved in cell proliferation and survival; targeted by HJD ingredients.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Indirect; downstream of AGE-RAGE signaling.", "mechanism": "AKT1 regulates cell survival and metabolism; modulated by HJD to improve MAFLD.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Indirect; inflammation downstream of AGE-RAGE.", "mechanism": "TNF promotes inflammation and hepatocyte injury in MAFLD.", "protein": "TNF", "relationship_type": "causal", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Indirect; downstream of AGE-RAGE.", "mechanism": "STAT3 mediates inflammatory and metabolic signaling in MAFLD.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Indirect; inflammation downstream of AGE-RAGE.", "mechanism": "IL1B promotes hepatic inflammation and progression of MAFLD.", "protein": "IL1B", "relationship_type": "causal", "source_pmcid": "PMC12129013" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Indirect; inflammation downstream of AGE-RAGE.", "mechanism": "PTGS2 (COX-2) involved in inflammatory response in MAFLD; targeted by HJD.", "protein": "PTGS2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129013" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Promotes differentiation of bone mesenchymal stem cells to osteoblasts via CXCL1 and CXCL8 up-regulation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12129198" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Elevated leptin in obesity has a dominantly detrimental effect on bone health, inhibiting bone formation via hypothalamic serotonin signaling.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects stability and receptor interaction.", "mechanism": "Inhibits osteoclast formation; reduced release in obesity increases bone resorption.", "protein": "Osteoprotegerin", "relationship_type": "protective", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Up-regulated by adiponectin, promotes osteoblast differentiation.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "protective", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Up-regulated by adiponectin, promotes osteoblast differentiation.", "protein": "CXCL8 (IL-8)", "relationship_type": "protective", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Obesity increases secondary hyperparathyroidism, elevating PTH and reducing BMD.", "protein": "Parathyroid hormone (PTH)", "relationship_type": "causal", "source_pmcid": "PMC12129198" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Leptin levels are elevated in obesity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Elevated ALP is associated with bone turnover and osteoporosis risk.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129198" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects stability and half-life.", "mechanism": "Lower albumin levels observed in higher ABSI quartiles, associated with lower BMD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129198" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation of apolipoproteins modulates LDL function.", "mechanism": "Elevated LDL-C in obesity increases cardiovascular risk.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC12129198" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "N-glycosylation affects albumin stability and function.", "mechanism": "Dynamic changes in serum albumin levels are predictive of DILI onset.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "GGT is a glycosylated membrane protein; glycosylation modulates activity.", "mechanism": "Elevated GGT is a marker of cholestatic liver injury in DILI.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "N-glycosylation regulates ALP secretion and activity.", "mechanism": "ALP elevation indicates cholestatic or mixed DILI.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "O-glycosylation affects proBNP processing and stability.", "mechanism": "Elevated proBNP associated with negative DILI prediction, possibly reflecting cardiac confounding.", "protein": "Pro-brain natriuretic peptide (proBNP)", "relationship_type": "protective", "source_pmcid": "PMC12129776" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "LDL particles contain glycoproteins (ApoB) with N-glycosylation affecting clearance.", "mechanism": "Dynamic changes in LDL-C are predictive of DILI risk.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "HDL contains glycoproteins (ApoA-I) with glycosylation modulating function.", "mechanism": "HDL-C changes are associated with DILI risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Bile acids are conjugated to glycine/taurine; glycoprotein transporters regulate secretion.", "mechanism": "Elevated TBA indicates impaired bile secretion in DILI.", "protein": "Total bile acids (TBA)", "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "HBeAg is a viral glycoprotein; glycosylation affects immunogenicity.", "mechanism": "HBeAg levels help exclude viral hepatitis as DILI etiology.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "ALT is not glycosylated but interacts with glycoprotein-rich membranes.", "mechanism": "Rapid increases in ALT are predictive of hepatocellular DILI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "AST is not glycosylated but may be affected by glycoprotein interactions.", "mechanism": "AST elevation is a marker for hepatocellular injury but may be confounded by cardiac injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129776" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "HDL-C has anti-inflammatory and anti-atherogenic properties, lowering CVD risk.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12129785" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "NHDL-C includes glycosylated apolipoproteins (e.g., ApoB).", "mechanism": "Elevated NHDL-C reflects increased atherogenic lipoproteins, predicting CVD risk.", "protein": "NHDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "high", "disease": "All-cause Mortality", "glycan_involvement": "Reflects balance of glycoprotein-rich lipoproteins.", "mechanism": "A U-shaped relationship: NHHR outside 2.8\u20133.2 range increases mortality risk.", "protein": "NHHR (NHDL-C/HDL-C ratio)", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Ratio integrates glycosylated lipoprotein components.", "mechanism": "NHHR predicts CVD mortality; both low and high extremes increase risk.", "protein": "NHHR (NHDL-C/HDL-C ratio)", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "medium", "disease": "All-cause Mortality", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect stability/activity.", "mechanism": "AST mediates the effect of NHHR on all-cause mortality, reflecting underlying liver/cardiac injury.", "protein": "AST", "relationship_type": "mediator", "source_pmcid": "PMC12129785" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "PCSK9 is N-glycosylated, affecting secretion and activity.", "mechanism": "Hcy upregulates PCSK9, increasing LDL-C and promoting atherosclerosis.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12129785" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-diabetic effects.", "mechanism": "Low HDL-C is associated with increased diabetes risk.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "low", "disease": "Gallstones", "glycan_involvement": "Glycosylation of HDL proteins may affect cholesterol transport.", "mechanism": "Altered HDL-C levels are linked to gallstone formation.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation may affect HDL function in bone metabolism.", "mechanism": "Low HDL-C is associated with increased osteoporosis risk.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12129785" }, { "confidence": "medium", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "LDL contains glycosylated ApoB; glycosylation affects receptor binding.", "mechanism": "Elevated LDL-C due to genetic defects increases CVD risk.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC12129785" }, { "confidence": "high", "disease": "Obesity-associated male infertility", "glycan_involvement": "INHB is a glycoprotein; glycosylation is essential for its secretion and bioactivity.", "mechanism": "Serum INHB levels decline with increasing BMI, reflecting impaired Sertoli cell function and reduced spermatogenesis.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "high", "disease": "Obesity-associated male infertility", "glycan_involvement": "AMH is a glycoprotein; glycosylation is required for proper folding and secretion.", "mechanism": "AMH levels decrease with increasing BMI, indicating Sertoli cell dysfunction and impaired testicular development.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "high", "disease": "Reduced spermatogenesis", "glycan_involvement": "Glycosylation affects INHB stability and endocrine function.", "mechanism": "Lower INHB levels are associated with reduced sperm concentration and total sperm count, especially in obese men.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Testicular dysfunction", "glycan_involvement": "Glycosylation is necessary for AMH secretion and receptor interaction.", "mechanism": "AMH reflects Sertoli cell activity; lower levels in obesity suggest testicular dysfunction.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Hypogonadism", "glycan_involvement": "Glycosylation is required for INHB endocrine activity.", "mechanism": "Obesity-induced hypogonadism may reduce INHB via impaired HPT axis and Sertoli cell function.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Hypogonadism", "glycan_involvement": "Glycosylation is essential for AMH stability and secretion.", "mechanism": "Obesity-related hypogonadism may lower AMH through HPT axis inhibition and altered sex hormone levels.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Testicular dysfunction", "glycan_involvement": "Glycosylation modulates INHB secretion and function.", "mechanism": "INHB decline in obesity reflects impaired Sertoli cell-germ cell interaction and testicular microenvironment.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Reduced spermatogenesis", "glycan_involvement": "Glycosylation affects AMH bioactivity.", "mechanism": "Lower AMH in obesity may indicate impaired spermatogenic potential.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Obesity-associated male infertility", "glycan_involvement": "Glycosylation is required for INHB secretion.", "mechanism": "Obesity-induced inflammation and metabolic dysfunction reduce INHB synthesis, contributing to infertility.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "causal", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Obesity-associated male infertility", "glycan_involvement": "Glycosylation is necessary for AMH endocrine function.", "mechanism": "Obesity impairs Sertoli cell function and AMH secretion, contributing to infertility.", "protein": "Anti-M\u00fcllerian Hormone (AMH)", "protein_enriched": { "function": "Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a r", "gene_name": "AMH", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P03971" }, "relationship_type": "causal", "source_pmcid": "PMC12129801" }, { "confidence": "medium", "disease": "Menopause", "glycan_involvement": "Glycosylation affects SOD1 stability and function.", "mechanism": "Zinc deficiency impairs SOD1 activity, reducing antioxidant defense and increasing oxidative stress, which contributes to ovarian aging and menopause.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates SOD1 antioxidant activity.", "mechanism": "Reduced SOD1 activity (due to low zinc) increases oxidative damage, contributing to CVD risk post-menopause.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "low", "disease": "Menopause", "glycan_involvement": "Altered glycosylation may affect albumin's antioxidant capacity.", "mechanism": "Serum albumin levels increase post-menopause, reflecting metabolic and oxidative changes.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129807" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation influences SOD1 secretion and function.", "mechanism": "SOD1 activity mitigates oxidative stress, which is linked to bone loss in postmenopausal women.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "low", "disease": "Premature Ovarian Insufficiency", "glycan_involvement": "Glycosylation may affect SOD1 localization and activity.", "mechanism": "SOD1 reduces oxidative damage in ovarian tissue, potentially delaying ovarian insufficiency.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate SOD1's vascular protective effects.", "mechanism": "SOD1 reduces ROS, which are implicated in hypertension development, especially post-menopause.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "low", "disease": "Cancer (Breast/Endometrial)", "glycan_involvement": "Glycosylation may affect SOD1's stability and tumor suppressor function.", "mechanism": "SOD1 activity reduces oxidative DNA damage, potentially lowering cancer risk associated with late menopause.", "protein": "Copper/Zinc Superoxide Dismutase (SOD1)", "relationship_type": "protective", "source_pmcid": "PMC12129807" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation mediates CD68 cell surface localization and recognition.", "mechanism": "CD68 antibody-conjugated Ce6 liposomes target foam cells, inhibit migration, and promote cholesterol efflux.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "high", "disease": "Breast Cancer (HER2+)", "glycan_involvement": "N-glycosylation affects HER2 receptor stability and antibody binding.", "mechanism": "HER2-targeted PDNS enable selective delivery of photosensitizers to HER2+ tumor cells.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "high", "disease": "Breast Cancer (TNBC)", "glycan_involvement": "N-glycosylation regulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 antibody delivered by PDNS blocks immune checkpoint, enhancing immunogenic cell death.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "medium", "disease": "Retinoblastoma", "glycan_involvement": "Glycosylation modulates FR cell surface expression and ligand binding.", "mechanism": "FR-targeted liposomal PDNS (FA-DOX-ICG-PFP@Lip) enable selective chemo/photothermal therapy.", "protein": "Folate Receptor (FR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation influences integrin conformation and ligand specificity.", "mechanism": "Peptide-modified PDNS target \u03b1v\u03b23 integrin for precise melanoma therapy.", "protein": "\u03b1v\u03b23 Integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation affects EGFR ligand binding and signaling.", "mechanism": "EGFR-TKI-based PDNS (HX103 probe) stratify NSCLC patients for targeted therapy.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12129894" }, { "confidence": "medium", "disease": "Breast Cancer (TNBC)", "glycan_involvement": "Glycosylation modulates CD47 cell surface expression and immune signaling.", "mechanism": "PDNS upregulate CD47 to enhance synergistic chemo/photodynamic therapy.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "Glycosylation may affect IDO1 stability and activity.", "mechanism": "PDNS deliver NLG919 to inhibit IDO1, boosting anti-tumor immunity.", "protein": "IDO1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "medium", "disease": "Breast Cancer (TNBC)", "glycan_involvement": "Glycosylation impacts Arg-1 secretion and enzymatic activity.", "mechanism": "PDNS suppress Arg-1 in M2 TAMs, reversing macrophage polarization and enhancing immune response.", "protein": "Arginase-1 (Arg-1)", "protein_enriched": { "function": "Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathway", "gene_name": "ARG1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05089" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "low", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "PDNS inhibit YAP to induce apoptosis and anti-angiogenesis.", "protein": "Yes-related protein (YAP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129894" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "ApoB is N-glycosylated, affecting its stability and receptor interactions.", "mechanism": "Elevated ApoB levels are associated with HP infection and increased cardiovascular risk.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "ApoA1 is glycosylated, influencing its anti-inflammatory properties.", "mechanism": "Reduced ApoA1 levels are observed in HP-positive patients, indicating impaired lipid metabolism.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Helicobacter pylori infection", "glycan_involvement": "Ratio reflects glycosylation status and balance of pro- and anti-inflammatory glycoproteins.", "mechanism": "Elevated ApoB/ApoA1 ratio is an independent risk factor for HP infection and cardiovascular risk.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates lipoprotein interactions with vascular endothelium.", "mechanism": "High ApoB/ApoA1 ratio promotes atherosclerosis progression in HP-infected individuals.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "causal", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Coronary heart disease", "glycan_involvement": "Glycosylation affects lipoprotein clearance and inflammation.", "mechanism": "Elevated ratio predicts increased risk of coronary heart disease in HP-positive patients.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation influences insulin sensitivity and lipid metabolism.", "mechanism": "High ratio is associated with increased diabetes risk in HP-infected individuals.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates lipoprotein function in adipose tissue.", "mechanism": "Elevated ratio correlates with obesity in HP-positive patients.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease", "glycan_involvement": "Glycosylation affects hepatic lipid transport.", "mechanism": "High ratio is linked to fatty liver in HP-infected individuals.", "protein": "ApoB/ApoA1 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation modulates ApoB's inflammatory signaling.", "mechanism": "ApoB is a strong inflammatory marker, positively correlated with IL-6 and CRP in HP infection.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "causal", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation enhances ApoA1's anti-inflammatory effects.", "mechanism": "ApoA1 inhibits neutrophil phagocytosis and ROS production, reducing inflammation in HP infection.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective", "source_pmcid": "PMC12129917" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "CD19 is a glycoprotein; glycosylation may affect antigen recognition.", "mechanism": "CD19 is highly expressed on B-ALL cells; CAR-T cells target CD19 to induce cytotoxicity.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Multiple myeloma (MM)", "glycan_involvement": "BCMA is glycosylated; glycosylation may influence surface expression.", "mechanism": "BCMA is overexpressed on malignant plasma cells in MM; CAR-T cells target BCMA.", "protein": "BCMA (B-cell maturation antigen)", "protein_enriched": { "function": "Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK", "gene_name": "TNFRSF17", "glycan_count": 13, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G05724UK", "G11629QQ", "G15169WU", "G22310AV", "G35242IF", "G60230HH", "G64527OM", "G70101JE", "G75983OB", "G79835GX", "G84452RH", "G86500WE", "G87618BG" ], "uniprot_id": "Q02223" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Large B-cell lymphoma (LBCL)", "glycan_involvement": "CD22 is a sialic acid-binding glycoprotein; glycosylation critical for ligand binding.", "mechanism": "CD22 is expressed on B-cell malignancies; CAR-T targeting CD22 is effective in relapsed/refractory LBCL.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Large B-cell lymphoma (LBCL)", "glycan_involvement": "CD20 is glycosylated; glycosylation may affect antibody binding.", "mechanism": "CD20 is overexpressed in >90% of B-cell lymphomas; CAR-T cells target CD20.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "medium", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "CD7 is a glycoprotein; glycosylation may affect surface expression and fratricide risk.", "mechanism": "CD7 is overexpressed on T-ALL and normal T cells; CAR-T targeting CD7 is under investigation.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "MESO is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "Mesothelin is highly expressed in ovarian cancer; CAR-T cells target MESO.", "protein": "Mesothelin (MESO)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GPC3 is a heparan sulfate proteoglycan; glycosaminoglycan chains are essential for function.", "mechanism": "GPC3 is highly expressed in HCC; CAR-T cells target GPC3.", "protein": "Glypican-3 (GPC3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Claudin 18.2 is a glycoprotein; glycosylation may affect cell surface localization.", "mechanism": "Claudin 18.2 is overexpressed in gastric cancer; CAR-T cells target Claudin 18.2.", "protein": "Claudin 18.2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation (truncated forms) creates tumor-specific epitopes.", "mechanism": "MUC1 is overexpressed and aberrantly glycosylated in breast cancer; CAR-T cells target MUC1.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "O-glycosylation (truncated forms) creates tumor-specific epitopes.", "mechanism": "MUC16 is overexpressed and aberrantly glycosylated in ovarian cancer; CAR-T cells target MUC16.", "protein": "MUC16", "protein_enriched": { "function": "Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces", "gene_name": "MUC16", "glycan_count": 23, "glycosylation_sites_count": 102, "glytoucan_ids": [ "G57321FI", "G62765YT", "G80920RR", "G49108TO", "G31852PQ", "G83460ZZ", "G27058EU", "G41247ZX", "G68040BX", "G27126ED", "G41429FA", "G25962JF", "G01650EU", "G37399XV", "G58498GJ", "G28541PG", "G49906RN", "G96430BV", "G64409MC", "G18647XP", "G63136LV", "G88891KO", "G43769HG" ], "uniprot_id": "Q8WXI7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12129935" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "FVIII is a heavily glycosylated protein; glycosylation affects its stability and secretion.", "mechanism": "Deficiency or dysfunction of FVIII leads to impaired coagulation and spontaneous bleeding.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "FIX is glycosylated; glycosylation influences its plasma half-life and activity.", "mechanism": "Deficiency or dysfunction of FIX impairs coagulation, causing bleeding episodes.", "protein": "Factor IX (FIX)", "relationship_type": "causal", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "BDD-FVIII retains essential glycosylation sites for function and secretion.", "mechanism": "AAV-mediated gene therapy delivers BDD-FVIII transgene to restore FVIII activity.", "protein": "BDD-FVIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "Glycosylation of FIX Padua is necessary for proper folding and activity.", "mechanism": "AAV-mediated gene therapy delivers codon-optimized FIX Padua transgene, increasing FIX activity.", "protein": "FIX Padua variant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130019" }, { "confidence": "medium", "disease": "Hemophilic arthropathy", "glycan_involvement": "Glycosylation ensures FVIII stability and therapeutic efficacy.", "mechanism": "Restoration of FVIII activity via gene therapy reduces bleeding and risk of joint damage.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "protective", "source_pmcid": "PMC12130019" }, { "confidence": "medium", "disease": "Hemophilic arthropathy", "glycan_involvement": "Glycosylation maintains FIX plasma stability.", "mechanism": "Restoration of FIX activity via gene therapy decreases bleeding and joint complications.", "protein": "Factor IX (FIX)", "relationship_type": "protective", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation status may affect assay results and FVIII detection.", "mechanism": "Baseline FVIII activity is used to classify disease severity and monitor therapy response.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "Glycosylation can influence FIX measurement accuracy.", "mechanism": "FIX activity levels are used to assess disease severity and therapeutic efficacy.", "protein": "Factor IX (FIX)", "relationship_type": "biomarker", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Essential glycosylation sites preserved for secretion and function.", "mechanism": "Codon-optimized BDD-FVIII gene therapy achieves sustained FVIII levels and reduces bleeding.", "protein": "BDD-FVIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Hemophilia B", "glycan_involvement": "Glycosylation required for proper FIX Padua folding and activity.", "mechanism": "Codon-optimized FIX Padua gene therapy results in higher FIX activity and reduced infusions.", "protein": "FIX Padua variant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130019" }, { "confidence": "high", "disease": "Symptomatic hypotension", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "SGLT2 inhibitors can exacerbate hypotension in older adults.", "protein": "SGLT2 (Sodium-glucose co-transporter 2)", "protein_enriched": { "function": "Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD", "gene_name": "SELENOK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6D0" }, "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation modulates SGLT2 stability and activity.", "mechanism": "SGLT2 inhibitors lower blood glucose by blocking renal glucose reabsorption.", "protein": "SGLT2 (Sodium-glucose co-transporter 2)", "protein_enriched": { "function": "Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD", "gene_name": "SELENOK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6D0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Bleeding complications", "glycan_involvement": "No direct glycan involvement; aspirin may affect glycoprotein-mediated platelet function.", "mechanism": "Aspirin inhibits platelet aggregation, increasing bleeding risk in older adults.", "protein": "Acetylsalicylic acid (Aspirin)", "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Cognitive impairment", "glycan_involvement": "No direct glycan involvement; anticholinergic drugs may interact with glycoprotein receptors.", "mechanism": "Pheniramine's anticholinergic effects can worsen cognition in older adults.", "protein": "Pheniramine", "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Falls", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Anticholinergic side effects increase fall risk.", "protein": "Pheniramine", "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "medium", "disease": "Multimorbidity", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Chronic corticosteroid use can exacerbate comorbidities.", "protein": "Hydrocortisone", "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Benzodiazepines impair cognition and increase fall risk.", "protein": "Clonazepam", "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Renal dysfunction", "glycan_involvement": "Glycosylation affects SGLT2 renal localization.", "mechanism": "SGLT2 inhibitors may worsen renal function in patients with low eGFR.", "protein": "SGLT2 (Sodium-glucose co-transporter 2)", "protein_enriched": { "function": "Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD", "gene_name": "SELENOK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6D0" }, "relationship_type": "causal", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Used for secondary prevention of cardiovascular events.", "protein": "Acetylsalicylic acid (Aspirin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Allergy/pruritus", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Used to treat allergy/pruritus but inappropriate in older adults due to side effects.", "protein": "Pheniramine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130026" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycosylation modulates fibrinogen's clotting function and plasma half-life.", "mechanism": "Elevated fibrinogen increases risk of thrombosis and poor stroke outcome.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "high", "disease": "Poor Functional Outcome after Stroke", "glycan_involvement": "N-glycosylation affects prothrombin activation and stability.", "mechanism": "Higher prothrombin time (PT) predicts worse functional recovery post-stroke.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "medium", "disease": "Poor Functional Outcome after Stroke", "glycan_involvement": "N-glycosylation influences albumin's stability and transport properties.", "mechanism": "Low serum albumin is associated with malnutrition and worse stroke prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "medium", "disease": "Atherogenesis", "glycan_involvement": "Glycosylation modulates ApoAI's lipid binding and anti-inflammatory functions.", "mechanism": "Altered ApoAI levels are linked to increased risk of atherosclerosis and stroke.", "protein": "Apolipoprotein AI", "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation affects ApoB's LDL particle formation and clearance.", "mechanism": "Elevated ApoB is associated with hyperlipidemia and increased stroke risk.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation is essential for CRP's ligand binding and immune activation.", "mechanism": "CRP elevation indicates systemic inflammation, which worsens stroke outcomes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "low", "disease": "Kidney Dysfunction", "glycan_involvement": "Glycosylation impacts globulin's immune and transport functions.", "mechanism": "Altered globulin levels may reflect renal impairment affecting stroke recovery.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "O-glycosylation of apo(a) modulates Lp(a) plasma levels and vascular effects.", "mechanism": "Elevated Lp(a) increases risk of thrombosis and ischemic stroke.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "low", "disease": "Malnutrition", "glycan_involvement": "N-glycosylation regulates transferrin's iron binding and serum half-life.", "mechanism": "Low transferrin may indicate malnutrition, impacting stroke recovery.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130038" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Fc N-glycosylation modulates IgG's effector functions and inflammatory potential.", "mechanism": "IgG 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"glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation at Asn297 is critical for Fc\u03b3R and C1q binding.", "mechanism": "Fc region interacts with Fc\u03b3Rs and complement to trigger cytotoxicity and phagocytosis.", "protein": "Fc region of IgG", "relationship_type": "protective", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "Complement-mediated cytotoxicity", "glycan_involvement": "Fc glycosylation modulates C1q binding efficiency.", "mechanism": "C1q binds Fc region of IgG on spike-expressing cells, activating complement cascade and cell lysis.", "protein": "Complement C1q", "relationship_type": "causal", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "Antibody-dependent cellular cytotoxicity", "glycan_involvement": "Fc glycan structure influences Fc\u03b3R affinity and ADCC potency.", "mechanism": "Fc\u03b3Rs on NK cells bind IgG Fc, triggering lysis of spike-expressing cells.", "protein": "Fc gamma receptor (Fc\u03b3R)", "relationship_type": "causal", "source_pmcid": "PMC12130042" }, { "confidence": "medium", "disease": "Antibody escape", "glycan_involvement": "Glycan shield may contribute to immune evasion.", "mechanism": "Spike mutations (Omicron, XBB.1.5, EG.5) reduce neutralizing antibody binding, but Fc-effector antibodies retain activity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "Vaccine-induced immunity", "glycan_involvement": "Glycosylation status may affect durability and quality of response.", "mechanism": "Post-booster, increased IgG titers correlate with enhanced protection and Fc-effector functions.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12130042" }, { "confidence": "medium", "disease": "COVID-19 (Omicron variant)", "glycan_involvement": "Fc glycan composition modulates effector function persistence.", "mechanism": "Non-neutralizing antibodies with Fc-effector activity provide protection against Omicron despite neutralization escape.", "protein": "Fc region of IgG", "relationship_type": "protective", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "Antibody-dependent cellular cytotoxicity", "glycan_involvement": "Fc glycosylation at Asn297 is essential for CD16 binding.", "mechanism": "CD16 on NK cells binds IgG Fc, mediating ADCC against spike-expressing cells.", "protein": "CD16 (Fc\u03b3RIII)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "COVID-19 (XBB.1.5 variant)", "glycan_involvement": "Variant-specific glycosylation may affect antibody accessibility.", "mechanism": "Spike is the antigenic target for vaccine-induced antibodies, including those mediating Fc-effector functions.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130042" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates lectin/selectin binding and scavenger receptor activity.", "mechanism": "Upregulated in monocytes during infection and severe disease; marker of inflammation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects cell-cell adhesion and immune synapse formation.", "mechanism": "Downregulated in severe COVID-19; involved in T cell activation and signaling.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for TCR complex stability and signaling.", "mechanism": "Downregulated in severe COVID-19; critical for T cell receptor signaling.", "protein": "CD3G", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P09693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions and cell migration.", "mechanism": "Upregulated in T cell activation during infection and vaccination; regulates lymphocyte trafficking.", "protein": "CCR7", "protein_enriched": { "function": "Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions", "gene_name": "CCR7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P32248" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation essential for receptor stability and ligand binding.", "mechanism": "Upregulated in monocytes, T cells, and B cells during immune activation post-vaccination.", "protein": "KIT", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maint", "gene_name": "KIT", "glycan_count": 26, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05724UK", "G06356OH", "G28541PG", "G37399XV", "G39446WN", "G45504EY", "G59626AS", "G80920RR", "G95865ZB", "G41247ZX", "G31852PQ", "G62765YT", "G23719VF", "G53075ES", "G61256FT", "G02528FI", "G10486CT", "G10773YW", "G45395BF", "G47644PP", "G57776ZS", "G57776ZU", "G94470IW" ], "uniprot_id": "P10721" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences receptor folding and immune inhibitory signaling.", "mechanism": "Upregulated in monocytes during infection; inhibitory receptor modulating antigen presentation.", "protein": "LILRB1", "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor surface expression and function.", "mechanism": "Upregulated in T cells during infection; regulates T cell activation.", "protein": "LILRB4", "protein_enriched": { "function": "Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles (PubMed:11169396, PubMed:12853576, PubMed:16455647, PubMed:20448110, PubMed:27859042). In", "gene_name": "LILRB2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q8N423" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates membrane organization and signaling.", "mechanism": "Upregulated in neutrophils post-vaccination; involved in cell activation and motility.", "protein": "TSPAN2", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Participates thereby in dive", "gene_name": "TSPAN1", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G18647XP", "G20210JR", "G23294PN", "G23719VF", "G27126ED", "G28541PG", "G29184RN", "G29299MO", "G31852PQ", "G32788FZ", "G37399XV", "G37818NZ", "G39188ZX", "G39446WN", "G40574BA", "G41247ZX", "G41840AI", "G43769HG", "G46503DX", "G47448YK", "G47702MW", "G51653BI", "G58954YZ", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G80920RR", "G82463GQ", "G85269DF", "G92050GC", "G92406TI", "G95865ZB", "G96091TT", "G00273SJ", "G00912UN", "G07246CJ", "G08918WF", "G25079LO", "G27947YN", "G40834TG", "G40926MX", "G41071NU", "G46691LC", "G49018RC", "G49755GI", "G49906RN", "G57776ZS", "G60033FS", "G64527OM", "G65184UU", "G68490OW", "G70441OD", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G79666IR", "G80479JV", "G85282JO", "G86880BF", "G87123QX", "G90659AW", "G98611JV", "G99668VU", "G99679NM", "G17187PH", "G12270AG" ], "uniprot_id": "O60635" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Glycosylation affects secretion and extracellular signaling.", "mechanism": "Highly upregulated in monocytes in severe disease; marker of inflammation.", "protein": "S100A9", "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "high", "disease": "Vaccine-induced immune response", "glycan_involvement": "Glycosylation modulates immune cell interactions and antigen presentation.", "mechanism": "Upregulated in monocytes/macrophages post-vaccination, indicating activation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130191" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1 kinase activity drives necroptosis and inflammation in sepsis; inhibition protects against lethality.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "high", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1 kinase activity mediates cell death and cytokine storm; inhibition by phensuximide reduces mortality and tissue damage.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Aberrant RIPK1 kinase activity contributes to inflammation and tissue damage.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1 kinase activity exacerbates inflammatory signaling.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "medium", "disease": "Ischemia", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1-dependent necroptosis contributes to cell death in ischemic injury.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1 kinase activity drives inflammatory cell death in skin.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "RIPK1 kinase activity implicated in neuroinflammation and degeneration.", "protein": "RIPK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130204" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TNFR1 is a glycoprotein; glycosylation required for proper folding and cell surface expression.", "mechanism": "TNFR1 activation triggers RIPK1-dependent necroptosis and inflammation.", "protein": "TNFR1", "relationship_type": "causal", "source_pmcid": "PMC12130204" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-8 is glycosylated; glycosylation affects stability and secretion.", "mechanism": "IL-8 is upregulated during RIPK1-mediated necroptosis and inflammation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130204" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "HMGB1 is released as a DAMP during necroptosis, promoting inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130204" }, { "confidence": "high", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "VWF glycosylation is essential for multimer formation and function.", "mechanism": "Elevated VWF:Ag and VWF:RCo levels indicate endothelial activation and correlate with disease severity and thrombosis risk.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130217" }, { "confidence": "high", "disease": "Thrombosis (DVT/PE)", "glycan_involvement": "Multimeric glycosylated VWF binds platelets via glycoprotein receptors.", "mechanism": "High VWF levels promote platelet adhesion and aggregation, increasing risk of thrombotic events in severe COVID-19.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC12130217" }, { "confidence": "high", "disease": "Acquired von Willebrand syndrome (AvWS)", "glycan_involvement": "Loss of glycosylated HMW multimers impairs hemostatic function.", "mechanism": "ECMO-induced shear stress and increased ADAMTS-13 activity cleave HMW VWF multimers, reducing VWF:RCo/VWF:Ag ratio and causing AvWS.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC12130217" }, { "confidence": "high", "disease": "Hemorrhage (intramuscular, GI, cerebral)", "glycan_involvement": "Glycosylation required for multimer stability and platelet binding.", "mechanism": "Loss of HMW VWF multimers in AvWS impairs primary hemostasis, increasing bleeding risk in ECMO patients.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "causal", "source_pmcid": "PMC12130217" }, { "confidence": "high", "disease": "Acquired von Willebrand syndrome (AvWS)", "glycan_involvement": "ADAMTS-13 recognizes glycosylated VWF multimers for cleavage.", "mechanism": "Enhanced ADAMTS-13 activity during ECMO cleaves VWF multimers, contributing to AvWS.", "protein": "ADAMTS-13", "relationship_type": "causal", "source_pmcid": "PMC12130217" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "FVIII is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Elevated FVIII levels reflect hypercoagulable state and correlate with severity.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130217" }, { "confidence": "medium", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "Glycosylation affects fibrinogen solubility and clot formation.", "mechanism": "Elevated fibrinogen indicates inflammation and hypercoagulability; decreased levels in ECMO patients associate with bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130217" }, { "confidence": "medium", "disease": "Thrombosis (DVT/PE)", "glycan_involvement": "Receptor glycosylation modulates VWF binding.", "mechanism": "VWF multimers bind platelet glycoprotein receptors, mediating platelet adhesion and aggregation.", "protein": "Platelet glycoprotein receptors", "relationship_type": "causal", "source_pmcid": "PMC12130217" }, { "confidence": "medium", "disease": "ARDS (acute respiratory distress syndrome)", "glycan_involvement": "Glycosylation required for VWF secretion and function.", "mechanism": "Elevated VWF reflects endothelial injury in ARDS secondary to COVID-19.", "protein": "von Willebrand factor (VWF)", "protein_enriched": { "function": "Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface", "gene_name": "VWF", "glycan_count": 203, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G73004SD", "G00912UN", "G01160VV", "G06247RL", "G08293MJ", "G08918WF", "G10486CT", "G16175ZV", "G27058EU", "G27947YN", "G31852PQ", "G37818NZ", "G40926MX", "G41247ZX", "G43223CG", "G45395BF", "G46503DX", "G57776ZS", "G59626AS", "G62765YT", "G68490OW", "G70232NH", "G79666IR", "G80920RR", "G83646BJ", "G84452RH", "G90659AW", "G92135MA", "G93718GY", "G99668VU", "G99679NM", "G04784US", "G06330RB", "G07799LX", "G11629QQ", "G15038BD", "G15169WU", "G20312EM", "G22310AV", "G25079LO", "G29279QO", "G33567AB", "G39595FH", "G41044JW", "G47518TP", "G48414YA", "G51413EV", "G59324HL", "G75568BH", "G77582RK", "G82830MN", "G83555HU", "G84664JR", "G85144OK", "G86752LQ", "G94917XT", "G39188ZX", "G00273SJ", "G02815KT", "G04657PL", "G10846ZT", "G27126ED", "G40834TG", "G43769HG", "G46691LC", "G51653BI", "G53075ES", "G60033FS", "G63980BQ", "G83460ZZ", "G87123QX", "G88374WZ", "G98611JV", "G15664MX", "G20706XG", "G23863VK", "G77669RF", "G81263BG", "G57321FI", "G13910DJ", "G43669FQ", "G56518TU", "G56784JY", "G80075MS", "G05962QB", "G13131HA", "G55132BD", "G60834IK", "G81637OR", "G86880BF", "G90382BL", "G14972EH", "G34989PA", "G37412TK", "G40574BA", "G47950XN", "G64409MC", "G83633GK", "G12341GU", "G25418HZ", "G31916IQ", "G41071NU", "G45526EA", "G52527GH", "G70619PT", "G75983OB", "G87661QW", "G04854VP", "G40206WX", "G72747WU", "G94470IW", "G01485JJ", "G01650EU", "G02030ZB", "G07755XJ", "G28541PG", "G42124LM", "G61256FT", "G76295SF", "G80223IX", "G86182NS", "G02886BB", "G06356OH", "G10488MI", "G23505EP", "G87389XI", "G92551JA", "G00031MO", "G01378OV", "G01614ZM", "G03382KH", "G03481FE", "G04689DA", "G05724UK", "G08242BT", "G12398HZ", "G12920QL", "G14950CY", "G15956KF", "G17095DP", "G18219CJ", "G18938DW", "G20425TQ", "G22625SJ", "G23432EQ", "G23453IV", "G23824AT", "G23901NY", "G25520XG", "G28723UT", "G29857RC", "G29880MM", "G29931IJ", "G31544HA", "G33262YZ", "G36191CD", "G41331JX", "G44215PV", "G45359RY", "G46687AB", "G46902YN", "G47012YE", "G47175EF", "G49108TO", "G50045TK", "G52567OL", "G52934AK", "G55396DW", "G58667NI", "G60215UL", "G63889NK", "G64527OM", "G66163OV", "G66265KN", "G66937TJ", "G67381VP", "G69411IG", "G70101JE", "G70822IO", "G70945OS", "G71013KY", "G71835BN", "G72718TT", "G72797UR", "G77149EE", "G78059CC", "G79568CQ", "G79809MM", "G81006GJ", "G81295CK", "G82955EQ", "G85479RL", "G86357DX", "G87073UP", "G87535DG", "G90093AU", "G91636VS", "G94192DA", "G97765TT", "G98719SR" ], "uniprot_id": "P04275" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130217" }, { "confidence": "low", "disease": "COVID-19-associated coagulopathy (CAC)", "glycan_involvement": "FIX glycosylation affects activity and plasma half-life.", "mechanism": "FIX activity remains at upper reference range, indicating altered coagulation in severe COVID-19.", "protein": "Factor IX (FIX)", "relationship_type": "biomarker", "source_pmcid": "PMC12130217" }, { "confidence": "high", "disease": "Chronic liver disease", "glycan_involvement": "Altered glycosylation affects stability and serum half-life.", "mechanism": "Reduced albumin secretion indicates hepatocyte dysfunction in chronic liver disease.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects membrane localization and transporter activity.", "mechanism": "MDR1 expression modulates drug efflux; altered function increases susceptibility to DILI.", "protein": "MDR1", "relationship_type": "biomarker", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "MRP1 mediates drug and metabolite export; dysfunction leads to intracellular accumulation and toxicity.", "protein": "MRP1", "relationship_type": "biomarker", "source_pmcid": "PMC12130281" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation modulates enzyme stability and substrate specificity.", "mechanism": "CYP3A4 metabolizes many drugs; altered activity can generate toxic metabolites.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "causal", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "CYP1A2 bioactivates drugs to reactive intermediates causing hepatocyte damage.", "protein": "CYP1A2", "protein_enriched": { "function": "", "gene_name": "10A19I.14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV2" }, "relationship_type": "causal", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects enzyme folding and function.", "mechanism": "CYP2B6 metabolizes xenobiotics; altered function may increase DILI risk.", "protein": "CYP2B6", "protein_enriched": { "function": "Transcription factor that binds to the DNA sequence 5'-CCAACC-3'. Regulates directly PME5, UND and GLOX1 (PubMed:21673079). Essential for tapetum development in anthers and microsporogenesis (PubMed:1", "gene_name": "MYB80", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV0" }, "relationship_type": "causal", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "CYP2C9 metabolizes drugs; polymorphisms and altered glycosylation impact toxicity.", "protein": "CYP2C9", "relationship_type": "causal", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "CYP7A1 is key in bile acid synthesis; reduced activity is linked to liver dysfunction.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130281" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Altered glycosylation may reflect hepatocyte stress.", "mechanism": "Decreased albumin secretion is an early marker of hepatocyte injury.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12130281" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation modulates drug efflux efficiency.", "mechanism": "Overexpression confers drug resistance in hepatoma cells.", "protein": "MDR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130281" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "GDNF is a glycosylated neurotrophic factor; glycosylation is required for secretion and stability.", "mechanism": "Astrocytic overexpression of GDNF increases astrocyte branching and process length, partially preserves hippocampal-dependent spatial memory.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130339" }, { "confidence": "high", "disease": "Sporadic Alzheimer's Disease (STZ model)", "glycan_involvement": "Glycosylation of GDNF is essential for its neuroprotective function.", "mechanism": "Prevents STZ-induced reduction in astrocyte process length and branching complexity, partially rescues spatial memory deficits.", "protein": "GDNF", "relationship_type": "protective", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for GDNF secretion; no direct glycan modulation of inflammation shown.", "mechanism": "Astrocyte-derived GDNF did not reduce microglial activation in STZ model, suggesting limited anti-inflammatory effect in vivo.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130339" }, { "confidence": "high", "disease": "Cognitive Impairment", "glycan_involvement": "Glycosylation required for GDNF function.", "mechanism": "Astrocytic GDNF overexpression partially preserves spatial memory but not recognition memory in STZ-induced cognitive deficit.", "protein": "GDNF", "relationship_type": "protective", "source_pmcid": "PMC12130339" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation required for GDNF stability and activity.", "mechanism": "GDNF protects dopaminergic neurons; clinical trials and gene therapy approaches target GDNF delivery.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "GFR\u03b11 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein; glycosylation affects receptor localization and function.", "mechanism": "Deficient GFR\u03b11 expression in AD neurons impairs response to GDNF, limiting neuroprotection.", "protein": "GFR\u03b11", "relationship_type": "causal", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "RET is glycosylated; glycosylation affects receptor function.", "mechanism": "RET is part of GDNF signaling; STZ-induced insulin resistance disrupts RET/Akt pathway, impairing GDNF neuroprotection.", "protein": "RET proto-oncogene", "relationship_type": "causal", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Sporadic Alzheimer's Disease (STZ model)", "glycan_involvement": "IGF1 is glycosylated; glycosylation required for secretion and activity.", "mechanism": "IGF1 ameliorates neuroinflammation and improves memory in STZ model.", "protein": "IGF1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect filament assembly.", "mechanism": "GFAP marks astrocyte activation and structural changes in neurodegeneration.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130339" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Iba1 is glycosylated; glycosylation may affect function.", "mechanism": "Iba1 marks microglial activation; increased reactive microglia in STZ model.", "protein": "Iba1 (AIF1)", "relationship_type": "biomarker", "source_pmcid": "PMC12130339" }, { "confidence": "high", "disease": "Ataxia-telangiectasia", "glycan_involvement": "Glycosylation of CD98HC is required for membrane localization and antiporter function.", "mechanism": "Loss of ATM-mediated phosphorylation of CD98HC impairs trafficking of amino acid antiporters, leading to glutamate accumulation and metabolic stress.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation required for CD98HC function in islet cells.", "mechanism": "Impaired CD98HC trafficking in pancreatic \u03b1 and \u03b2 cells leads to glutamate toxicity, reduced hormone secretion, and glucose intolerance.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Fatty liver disease", "glycan_involvement": "Glycosylation of CD98HC necessary for antiporter activity.", "mechanism": "Loss of ATM-CD98HC axis in pancreatic \u03b1-cells reduces glucagon secretion, promoting hepatic lipid accumulation.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Telangiectasia", "glycan_involvement": "Glycosylation required for membrane localization in endothelial cells.", "mechanism": "Impaired CD98HC-dependent arginine transport in endothelial cells disrupts angiogenesis and vessel integrity.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Glutamate toxicity", "glycan_involvement": "Glycosylation required for antiporter function.", "mechanism": "Defective antiporter trafficking leads to intracellular glutamate accumulation, causing toxicity in multiple tissues.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Pancreatic islet dysfunction", "glycan_involvement": "Glycosylation required for antiporter assembly and function.", "mechanism": "ATM-CD98HC axis disruption impairs glutamate/cystine exchange, leading to \u03b1 and \u03b2 cell dysfunction and hormone secretion defects.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation required for antiporter trafficking.", "mechanism": "Reduced arginine import via CD98HC-y+LAT antiporter impairs nitric oxide synthesis and angiogenesis.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Glucose intolerance", "glycan_involvement": "Glycosylation required for antiporter function.", "mechanism": "Impaired antiporter function in islet cells leads to defective insulin and glucagon secretion, causing glucose intolerance.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Glycosylation required for antiporter function in immune cells.", "mechanism": "CD98HC-dependent amino acid transport is essential for immune cell function; ATM loss impairs this pathway.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "medium", "disease": "Cancer predisposition", "glycan_involvement": "Glycosylation required for antiporter function.", "mechanism": "Impaired redox and amino acid homeostasis via CD98HC may contribute to genomic instability and cancer risk in A-T.", "protein": "CD98 heavy chain (CD98HC)", "relationship_type": "causal", "source_pmcid": "PMC12130354" }, { "confidence": "high", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c is a component of the eGDR index, which inversely correlates with MAFLD risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "N-glycosylation is essential for insulin receptor function and signaling.", "mechanism": "Reduced insulin receptor responsiveness promotes hepatic lipid accumulation and fibrosis.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12130497" }, { "confidence": "medium", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "Albumin is N-glycosylated, affecting its stability and function.", "mechanism": "Lower albumin levels are associated with increased MAFLD risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130497" }, { "confidence": "medium", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "GGT is glycosylated, which affects its secretion and activity.", "mechanism": "Elevated GGT is associated with hepatic steatosis and fibrosis in MAFLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130497" }, { "confidence": "medium", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "ALT is glycosylated, impacting its stability.", "mechanism": "Elevated ALT indicates liver injury and is associated with MAFLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "Apolipoproteins in VLDL are glycosylated, affecting lipid transport.", "mechanism": "Overproduction of VLDL due to insulin resistance leads to hepatic lipid accumulation.", "protein": "Triglyceride-rich lipoproteins (VLDL)", "relationship_type": "causal", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Metabolic associated fatty liver disease (MAFLD)", "glycan_involvement": "Apolipoproteins in HDL are glycosylated, influencing anti-inflammatory properties.", "mechanism": "Higher HDL-C is associated with lower MAFLD risk; part of AIP calculation.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12130497" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "TGF\u03b2 glycosylation modulates receptor binding and signaling.", "mechanism": "TGF\u03b2 mediates hepatic stellate cell activation and fibrosis in insulin resistance.", "protein": "Transforming growth factor beta (TGF\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation is required for receptor trafficking and function.", "mechanism": "Insulin receptor dysfunction leads to insulin resistance and diabetes.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycation of hemoglobin is a non-enzymatic glycan modification.", "mechanism": "HbA1c reflects chronic glucose exposure and is used to diagnose diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130497" }, { "confidence": "high", "disease": "Aging/longevity", "glycan_involvement": "FLR-2 is a glycoprotein hormone; glycosylation likely required for secretion and receptor interaction.", "mechanism": "FLR-2 neuropeptide released from interneurons binds FSHR-1 in intestine, activating p38-MAPK and promoting longevity.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "Osmotic stress intolerance", "glycan_involvement": "Glycosylation of FLR-2 may affect stability and signaling.", "mechanism": "FLR-2-FSHR-1 signaling activates p38-MAPK, increasing osmotic stress tolerance.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "medium", "disease": "Altered feeding behaviour", "glycan_involvement": "Glycosylation may influence neuropeptide-receptor interaction.", "mechanism": "FLR-2 signaling modulates foraging preference for B12-rich diet via neuron-gut axis.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "Aging/longevity", "glycan_involvement": "FSHR-1 is a glycoprotein receptor; glycosylation likely affects ligand binding.", "mechanism": "FSHR-1 acts as FLR-2 receptor in intestine, required for p38-MAPK activation and lifespan extension.", "protein": "FSHR-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "Osmotic stress intolerance", "glycan_involvement": "Glycosylation may be required for receptor function.", "mechanism": "FSHR-1 mediates FLR-2 signal to activate p38-MAPK, conferring stress tolerance.", "protein": "FSHR-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "medium", "disease": "Defecation defect", "glycan_involvement": "Glycoprotein nature may affect neuropeptide function.", "mechanism": "FLR-2 mutation suppresses defecation defects of class 1 flr mutants.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "Cytoprotective gene dysregulation", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "FLR-2-FSHR-1 axis required for CyTP gene expression via p38-MAPK.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "Cytoprotective gene dysregulation", "glycan_involvement": "Glycosylation likely required for receptor function.", "mechanism": "FSHR-1 required for FLR-2-induced CyTP gene expression.", "protein": "FSHR-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130505" }, { "confidence": "low", "disease": "Neurological disorders (by analogy to human glycoprotein hormones)", "glycan_involvement": "Glycosylation essential for hormone function in mammals.", "mechanism": "Homology to human glycoprotein hormones (e.g., thyrostimulin) implicated in neuroendocrine regulation.", "protein": "FLR-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "potential causal", "source_pmcid": "PMC12130505" }, { "confidence": "low", "disease": "Metabolic disorders (by analogy to human FSHR)", "glycan_involvement": "Glycosylation required for receptor function in mammals.", "mechanism": "Homology to human FSHR, which is involved in metabolic regulation.", "protein": "FSHR-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "potential causal", "source_pmcid": "PMC12130505" }, { "confidence": "high", "disease": "High-grade serous ovarian cancer (HGSOC)", "glycan_involvement": "CD36 is a glycoprotein; glycosylation is required for its cell surface localization and function.", "mechanism": "High CD36 expression in tumor vasculature correlates with unfavorable overall survival and residual disease.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "high", "disease": "Ovarian cancer (general)", "glycan_involvement": "Glycosylation is essential for CD36 receptor function.", "mechanism": "CD36 mediates uptake of lipids (glycerophospholipids, oxLDL) supporting tumor metabolism and progression.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "High-grade serous ovarian cancer (HGSOC)", "glycan_involvement": "LCN2 is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "LCN2 overexpression in ascites correlates with CD36 abundance and is involved in lipid metabolism and cell proliferation.", "protein": "LCN2", "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "High-grade serous ovarian cancer (HGSOC)", "glycan_involvement": "CFHR1 is a glycoprotein; glycosylation modulates complement regulation.", "mechanism": "CFHR1 overexpression in ascites correlates with CD36 abundance and lipid metabolism.", "protein": "CFHR1", "protein_enriched": { "function": "Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with li", "gene_name": "CFHR1", "glycan_count": 36, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G10846ZT", "G11314AS", "G26330YA", "G27058EU", "G27947YN", "G28681TP", "G35029YA", "G36379GD", "G40574BA", "G45395BF", "G45504EY", "G48414YA", "G57317CE", "G57776ZU", "G57888GL", "G59626AS", "G70232NH", "G72747WU", "G72787SB", "G82830MN", "G92275SC", "G95865ZB", "G23719VF", "G23863VK", "G44215PV", "G46902YN", "G52527GH", "G65184UU", "G75983OB", "G84452RH" ], "uniprot_id": "Q03591" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "High-grade serous ovarian cancer (HGSOC)", "glycan_involvement": "CFHR4 is a glycoprotein; glycosylation modulates complement regulation.", "mechanism": "CFHR4 overexpression in ascites correlates with CD36 abundance and lipid metabolism.", "protein": "CFHR4", "protein_enriched": { "function": "Involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism", "gene_name": "CFHR4", "glycan_count": 16, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G22310AV", "G32788FZ", "G45395BF", "G47518TP", "G48414YA", "G52527GH", "G56518TU", "G56784JY", "G62461SM", "G70232NH", "G82830MN", "G86880BF" ], "uniprot_id": "Q92496" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "Ovarian cancer (general)", "glycan_involvement": "Osteopontin is heavily glycosylated; glycosylation affects cell adhesion and migration.", "mechanism": "Serum osteopontin positively correlates with CD36 abundance and is associated with chemoresistance and poor prognosis.", "protein": "Osteopontin", "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "Ovarian cancer (general)", "glycan_involvement": "CXCL16 is glycosylated; glycosylation affects receptor binding and function.", "mechanism": "Serum CXCL16 correlates with CD36 abundance and promotes peritoneal metastasis, invasion, and migration.", "protein": "CXCL16", "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "Ovarian cancer (general)", "glycan_involvement": "CCL3 is glycosylated; glycosylation modulates chemokine activity.", "mechanism": "Serum CCL3 correlates with CD36 abundance and is associated with tumor progression.", "protein": "CCL3", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependen", "gene_name": "CCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130507" }, { "confidence": "high", "disease": "Metastatic cancer", "glycan_involvement": "Glycosylation is required for CD36 function in lipid uptake and cell signaling.", "mechanism": "CD36 expression increases with tumor burden and is associated with metastasis and progression in multiple cancers.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12130507" }, { "confidence": "medium", "disease": "Chemoresistance (in ovarian cancer)", "glycan_involvement": "Glycosylation is necessary for CD36 cell surface expression and function.", "mechanism": "CD36-mediated metabolic reprogramming supports survival and resistance to chemotherapy.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12130507" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "N-glycosylation required for proper folding and antigen presentation.", "mechanism": "Altered assembly and antigen presentation due to genomic and transcriptomic changes in MM plasma cells.", "protein": "MHC class II protein complex", "relationship_type": "causal", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation modulates cell adhesion and tumor microenvironment.", "mechanism": "ECM proteoglycan pathway dysregulation linked to MM progression.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation critical for collagen stability and ECM structure.", "mechanism": "Collagen formation and trimerization pathways altered in MM, affecting bone marrow niche.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation affects cytokine secretion and receptor binding.", "mechanism": "Serum IL-20 concentrations participate in MM progression and inflammation.", "protein": "IL20", "relationship_type": "biomarker", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation modulates cytokine stability and activity.", "mechanism": "IL24 injection reduces tumor size in mouse models.", "protein": "IL24", "relationship_type": "protective", "source_pmcid": "PMC12130518" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell adhesion and tumor progression.", "mechanism": "Used for plasma cell identification and enrichment in MM diagnosis.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "N-glycosylation affects enzyme activity and localization.", "mechanism": "Upregulated in MM; involved in protein folding and ER stress response.", "protein": "Protein disulfide isomerase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "GPCR glycosylation modulates receptor trafficking and signaling.", "mechanism": "Associated with drug resistance in MM cell lines.", "protein": "GPR183", "protein_enriched": { "function": "Dephosphorylates specifically the 5' and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides, and so protects mitochondrial DNA replication from excess dTTP. Has only marginal activity toward", "gene_name": "NT5M", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NPB1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "GPCR glycosylation affects immune cell signaling.", "mechanism": "CNV loss in MM; related to B cell number and prognosis.", "protein": "GPR18", "protein_enriched": { "function": "G protein-coupled receptor (GPCR) that plays a role in diverse physiological processes particularly within the immune and nervous systems (PubMed:21732409, PubMed:26195725). Becomes active when trigge", "gene_name": "GPR18", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q14330" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130518" }, { "confidence": "medium", "disease": "Diseases of glycosylation", "glycan_involvement": "Essential for Golgi glycoprotein trafficking and glycan processing.", "mechanism": "COG3 gene variation linked to glycosylation disorders in MM.", "protein": "COG3", "relationship_type": "causal", "source_pmcid": "PMC12130518" }, { "confidence": "high", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "PGRN is a lysosomal glycoprotein; glycosylation is essential for its lysosomal targeting and function.", "mechanism": "Haploinsufficiency or loss-of-function mutations in GRN cause PGRN deficiency, leading to lysosomal dysfunction, lipid dysregulation, neuroinflammation, and neurodegeneration.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "causal", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Neuronal ceroid lipofuscinosis (NCL)", "glycan_involvement": "Glycosylation required for lysosomal function of PGRN.", "mechanism": "Homozygous GRN mutations cause complete PGRN loss, resulting in lysosomal storage of lipofuscin and neurodegeneration.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "causal", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Glycosylation affects PGRN stability and trafficking.", "mechanism": "GRN variants and PGRN deficiency increase risk, correlate with amyloid-\u03b2 and tau pathology, and neuroinflammation.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "risk factor/therapeutic_target", "source_pmcid": "PMC12130522" }, { "confidence": "medium", "disease": "Parkinson's disease (PD)", "glycan_involvement": "Glycosylation required for lysosomal targeting.", "mechanism": "GRN variants and reduced PGRN levels are associated with increased PD risk, possibly via impaired lysosomal degradation of \u03b1-synuclein.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "risk factor/therapeutic_target", "source_pmcid": "PMC12130522" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "GRN variants associated with earlier onset and shorter survival; PGRN modulates neuroinflammation.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "risk factor", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Gaucher disease", "glycan_involvement": "PGRN glycosylation required for lysosomal function.", "mechanism": "PGRN regulates GCase activity and trafficking; deficiency exacerbates GCase substrate accumulation and pathology.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "modifier/therapeutic_target", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "GM2 gangliosidosis", "glycan_involvement": "PGRN glycosylation required for lysosomal function.", "mechanism": "PGRN deficiency reduces HexA activity, impairs ganglioside catabolism, and increases GM2 accumulation.", "protein": "Progranulin (PGRN)", "protein_enriched": { "function": "Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807", "gene_name": "GRN", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G80920RR", "G31852PQ", "G41247ZX", "G41429FA", "G43769HG", "G62765YT", "G83460ZZ", "G92050GC", "G49108TO", "G08290VR", "G11314AS", "G14669DU", "G15664MX", "G23719VF", "G27058EU", "G28681TP", "G31685JQ", "G37509XX", "G47644PP", "G47950XN", "G57776ZU", "G59626AS", "G63628AV", "G64409MC", "G64527OM", "G70101JE", "G72747WU", "G79666IR", "G92275SC", "G95865ZB" ], "uniprot_id": "P28799" }, "relationship_type": "modifier/therapeutic_target", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Frontotemporal dementia (FTD)", "glycan_involvement": "TMEM106B is a glycosylated lysosomal protein; glycosylation affects its function.", "mechanism": "TMEM106B variants modify FTD risk in GRN mutation carriers by affecting lysosomal function and lipid metabolism.", "protein": "TMEM106B", "protein_enriched": { "function": "Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the", "gene_name": "MGAT4A", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9UM21" }, "relationship_type": "modifier", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APOE is a glycoprotein; glycosylation affects lipid binding and receptor interactions.", "mechanism": "APOE4 isoform disrupts lipid metabolism, increases amyloid-\u03b2 and tau aggregation, and impairs microglial function.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/risk factor", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Parkinson's disease (PD)", "glycan_involvement": "GCase is a glycoprotein; glycosylation required for folding and lysosomal targeting.", "mechanism": "GBA mutations reduce GCase activity, leading to glucosylceramide accumulation, lysosomal dysfunction, and \u03b1-synuclein aggregation.", "protein": "\u03b2-glucocerebrosidase (GCase)", "relationship_type": "causal/risk factor", "source_pmcid": "PMC12130522" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Occludin is N-glycosylated, which affects its localization and function", "mechanism": "5-MIAA increases OCLN expression, enhancing tight junctions and barrier function", "protein": "OCLN (Occludin)", "relationship_type": "protective", "source_pmcid": "PMC12130558" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "TNF glycosylation modulates its secretion and activity", "mechanism": "5-MIAA reduces TNF expression, alleviating inflammation in intestinal cells", "protein": "TNF (Tumor Necrosis Factor)", "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Bacterial glycoproteins mediate host-pathogen interactions", "mechanism": "Porphyromonas abundance is reduced in centenarians, lowering risk of periodontitis", "protein": "Porphyromonas gingivalis glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Bacterial glycoproteins may influence metabolite production", "mechanism": "Lactobacillus-derived 5-MIAA activates Nrf2, protecting against oxidative liver injury", "protein": "Lactobacillus rhamnosus glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Chronic diseases (general)", "glycan_involvement": "Albumin glycosylation affects its stability and function", "mechanism": "Lower ALB in centenarians may reflect adaptation to aging and lower chronic disease risk", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Oral caries", "glycan_involvement": "Bacterial glycoproteins contribute to biofilm formation", "mechanism": "Reduced Propionibacterium in healthy centenarians lowers risk of caries", "protein": "Propionibacterium acidifaciens glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "CRP glycosylation modulates its immune function", "mechanism": "CRP levels used to assess inflammatory status in centenarians", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "Hemoglobin glycosylation (HbA1c) is a marker of metabolic health", "mechanism": "Lower HGB in centenarians may reflect adaptation to aging", "protein": "Hemoglobin (HGB)", "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "low", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects enzyme stability", "mechanism": "Higher AST in centenarians may indicate mild age-related liver changes", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "low", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects enzyme activity", "mechanism": "Lower ALT in centenarians may reflect healthy liver function", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130558" }, { "confidence": "high", "disease": "Gallbladder mucocele", "glycan_involvement": "Mucin is a heavily O-glycosylated glycoprotein; glycosylation is essential for mucus gel formation.", "mechanism": "Mucin hypersecretion leads to abnormal mucus accumulation in the gallbladder lumen, forming a mucocele.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Porcelain Gallbladder (PGB)", "glycan_involvement": "Altered glycosylation of mucin may affect viscosity and aggregation, exacerbating obstruction.", "mechanism": "Mucin hypersecretion contributes to cystic duct obstruction and bile stasis, promoting fibrosis and calcification.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Chronic cholecystitis", "glycan_involvement": "CD3 is N-glycosylated, which affects T-cell receptor function and migration.", "mechanism": "CD3+ T lymphocytes indicate immune cell infiltration in chronic inflammation.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130736" }, { "confidence": "low", "disease": "Chronic cholecystitis", "glycan_involvement": "PAX5 is a nuclear glycoprotein; glycosylation may regulate nuclear localization.", "mechanism": "PAX5+ B lymphocytes reflect B-cell presence in chronic inflammatory infiltrates.", "protein": "PAX5", "protein_enriched": { "function": "Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:10811620, PubMed:27181361). Fulfills a dual role by repressing B-lineage ina", "gene_name": "PAX5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02548" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130736" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "cPL is glycosylated, which may affect secretion and stability.", "mechanism": "Elevated cPL indicates pancreatic inflammation.", "protein": "Canine pancreatic lipase (cPL)", "relationship_type": "biomarker", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Porcelain Gallbladder (PGB)", "glycan_involvement": "ALKP is N-glycosylated, influencing its serum half-life.", "mechanism": "Increased ALKP reflects cholestasis and gallbladder wall injury.", "protein": "Alkaline phosphatase (ALKP)", "relationship_type": "biomarker", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Porcelain Gallbladder (PGB)", "glycan_involvement": "GGT is N-glycosylated, affecting its membrane localization.", "mechanism": "Elevated GGT is associated with biliary tract injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Chronic cholecystitis", "glycan_involvement": "O-glycosylation of mucin modulates its protective and pathological roles.", "mechanism": "Mucin hypersecretion can promote chronic inflammation by obstructing bile flow.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12130736" }, { "confidence": "medium", "disease": "Cholelithiasis", "glycan_involvement": "Glycosylation affects mucin's ability to nucleate gallstones.", "mechanism": "Excess mucin can trap bile salts and cholesterol, promoting gallstone formation.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12130736" }, { "confidence": "low", "disease": "Gallbladder cancer (GBC)", "glycan_involvement": "Aberrant glycosylation patterns are linked to tumorigenesis.", "mechanism": "Chronic mucin overproduction and inflammation may predispose to neoplastic transformation.", "protein": "Mucin", "relationship_type": "risk factor", "source_pmcid": "PMC12130736" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Enzyme acts on glycosidic bonds of dietary carbohydrates; glycosylation affects enzyme stability and localization.", "mechanism": "Inhibition of \u03b1-glucosidase reduces postprandial glucose absorption, lowering blood glucose.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130905" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Substrate specificity for glycosidic linkages; glycosylation modulates enzyme activity.", "mechanism": "Inhibition delays carbohydrate digestion, reducing hyperglycemia.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "GLUT4 is N-glycosylated, which is essential for its trafficking and function.", "mechanism": "Plant extracts enhance GLUT4-mediated glucose uptake in adipose and muscle tissue.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "protective", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Diabetes-associated hyperlipidemia", "glycan_involvement": "Glycosylation affects enzyme secretion and function.", "mechanism": "Inhibition improves lipid profile by reducing glucose-induced dyslipidemia.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Diabetes-induced nephropathy", "glycan_involvement": "Glycosylation status may influence enzyme clearance and tissue distribution.", "mechanism": "Inhibition reduces hyperglycemia, indirectly protecting renal function.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "protective", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Diabetes-induced hepatopathy", "glycan_involvement": "Glycosylation modulates enzyme stability in hepatic tissue.", "mechanism": "Lowering blood glucose reduces hepatic stress and damage.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "protective", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect detection and quantification in assays.", "mechanism": "Activity levels correlate with disease state and therapeutic response.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12130905" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "N-glycosylation required for proper membrane localization.", "mechanism": "Upregulation or enhanced translocation improves glycemic control.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12130905" }, { "confidence": "high", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Not directly discussed; ferritin is known to be glycosylated, but specific glycan changes in CAP are not described.", "mechanism": "Serum ferritin levels are elevated in severe CAP and correlate with disease severity and poor prognosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "high", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Not specified.", "mechanism": "High serum ferritin at admission predicts risk of mechanical ventilation, ICU admission, vasoactive agent use, death, and longer hospital stay.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Not specified.", "mechanism": "Ferritin may participate in CAP pathogenesis via iron metabolism and inflammatory signaling (NF-\u03baB, Nrf-2 activation).", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "causal", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Elevated serum ferritin is associated with severity in COVID-19, including acute liver injury and ICU transfer.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Not specified.", "mechanism": "Initial serum ferritin is upregulated in ARDS.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Not specified.", "mechanism": "Ferritin expression is increased and inversely associated with pulmonary function in COPD.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Higher ferritin mRNA expression in kidney correlates with metastasis and poor prognosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Not specified.", "mechanism": "Higher serum ferritin elevates risk of metabolic syndrome in childhood.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "low", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Not specified.", "mechanism": "Potential for anti-ferritin therapy in CAP suggested, but not yet validated.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131277" }, { "confidence": "high", "disease": "Community-acquired pneumonia (CAP)", "glycan_involvement": "Not specified.", "mechanism": "Serum ferritin has higher predictive power for death than CAP severity scores and routine blood indices.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131277" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation affects stability and half-life.", "mechanism": "Serum albumin levels decrease with worsening liver function and fibrosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131374" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation required for membrane localization and activity.", "mechanism": "Elevated GGT indicates biliary injury and cholestasis, especially in BDL models.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation critical for transporter function.", "mechanism": "Downregulation impairs bile acid secretion, contributing to cholestasis in BDL females.", "protein": "Abcc2 (MRP2)", "relationship_type": "causal", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "N-glycosylation affects cell surface expression.", "mechanism": "Reduced expression impairs bile acid uptake, exacerbating cholestasis.", "protein": "Slc10a1 (NTCP)", "relationship_type": "causal", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Downregulation in BDL females leads to impaired estrogen inactivation, promoting vascular protection.", "protein": "Sult1e1", "protein_enriched": { "function": "Site-specific tyrosine recombinase, which acts by catalyzing the cutting and rejoining of the recombining DNA molecules. Binds cooperatively to specific DNA consensus sequences that are separated from", "gene_name": "xerC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55888" }, "relationship_type": "protective", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation required for enzymatic function.", "mechanism": "Downregulation in BDL females reduces estrogen clearance, contributing to milder disease.", "protein": "Ugt2a3", "relationship_type": "protective", "source_pmcid": "PMC12131374" }, { "confidence": "high", "disease": "Sinusoidal capillarization", "glycan_involvement": "Glycosylation regulates cell-cell interactions.", "mechanism": "Loss of LSEC phenotype and increased capillarization associated with fibrosis and portal hypertension.", "protein": "LSEC markers (e.g., CD31/PECAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Kupffer cell activation increases thromboxane A2, raising portal pressure.", "protein": "Thromboxane A2 receptor (TBXA2R)", "relationship_type": "causal", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Downregulation in BDL females impairs estrogen metabolism, contributing to sex differences in disease severity.", "protein": "Cyp1a2", "relationship_type": "biomarker", "source_pmcid": "PMC12131374" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Upregulation in TAA females supports preserved estrogen metabolism.", "protein": "Cyp1a1", "relationship_type": "biomarker", "source_pmcid": "PMC12131374" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "PRL is a glycoprotein; glycosylation may affect stability and receptor binding, but specific glycan changes not detailed.", "mechanism": "Disrupted circadian rhythm of PRL due to social jetlag leads to decreased hepatic PRL signaling, promoting lipogenesis and fatty liver.", "protein": "Prolactin (PRL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may influence PRL bioactivity; not specifically addressed.", "mechanism": "Restoration of PRL rhythm (timed PRL administration) alleviates SJL-induced fatty liver.", "protein": "Prolactin (PRL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131380" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Suppressed hepatic CCND1 (downstream of PRL/MAPK) increases lipogenic enzymes, promoting steatosis.", "protein": "Cyclin D1 (CCND1)", "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "FASN is glycosylated; glycosylation may affect enzyme activity, but not discussed.", "mechanism": "Upregulated FASN (due to low PRL/CCND1) increases hepatic lipid synthesis.", "protein": "Fatty Acid Synthase (FASN)", "protein_enriched": { "function": "Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:12107171, PubMed:26431207, PubMed:2879", "gene_name": "Ddb1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q3U1J4" }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ACC is glycosylated; functional impact not discussed.", "mechanism": "Upregulated ACC (due to low PRL/CCND1) increases hepatic lipid synthesis.", "protein": "Acetyl-CoA Carboxylase (ACC)", "protein_enriched": { "function": "Voltage-gated chloride channel involved in high-concentration salt taste sensation (PubMed:34429071). Depolarization induced by high NaCl concentration may trigger the activation of TMC4-mediated chlo", "gene_name": "Tmc4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q7TQ65" }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "STAT3 is glycosylated; not specifically discussed.", "mechanism": "PRL signaling via STAT3 may regulate CCND1 and lipid metabolism; disruption contributes to steatosis.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "MAPK14 is glycosylated; not specifically discussed.", "mechanism": "PRL activates MAPK14, which upregulates CCND1; jetlag suppresses this pathway, promoting lipogenesis.", "protein": "MAPK14", "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ROR\u03b1 is glycosylated; not discussed.", "mechanism": "Jetlag impairs ROR\u03b1 binding to PRL promoter, reducing PRL transcription and leading to fatty liver.", "protein": "ROR\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "CIDEA is glycosylated; not discussed.", "mechanism": "Upregulated CIDEA in jetlag increases hepatic lipid accumulation.", "protein": "CIDEA", "protein_enriched": { "function": "Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recy", "gene_name": "DNAJC7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99615" }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Per3 is glycosylated; not discussed.", "mechanism": "Altered Per3 expression in jetlag disrupts circadian regulation of hepatic metabolism.", "protein": "Per3", "protein_enriched": { "function": "May be involved in BMP2-induced transcription", "gene_name": "ZBTB24", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43167" }, "relationship_type": "causal", "source_pmcid": "PMC12131380" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "TGF-\u03b2 released by macrophages activates JNK pathway, driving MDB formation and inflammation.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "N-glycosylation modulates receptor stability and signaling.", "mechanism": "Upregulated in MDB pathogenesis, mediates TGF-\u03b2 signaling to JNK.", "protein": "TGF-\u03b2R1", "relationship_type": "causal", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "Potential glycosylation may affect aggregation.", "mechanism": "Upregulated by c-JUN downstream of JNK; essential for MDB formation.", "protein": "UbD", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131408" }, { "confidence": "medium", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "O-glycosylation may regulate filament assembly.", "mechanism": "Aggregates with p62 in MDBs; upregulated in disease.", "protein": "K8", "relationship_type": "biomarker", "source_pmcid": "PMC12131408" }, { "confidence": "medium", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "Glycosylation may affect aggregate formation.", "mechanism": "Co-localizes with K8 in MDBs; marker of protein aggregation.", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131408" }, { "confidence": "medium", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "Glycosylation may regulate membrane targeting.", "mechanism": "Upregulated and released with mtDNA in MDVs during MDB formation.", "protein": "TOM20", "protein_enriched": { "function": "Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide", "gene_name": "TOMM20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q15388" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "Glycosylation may modulate DNA sensing.", "mechanism": "Activated by mtDNA from damaged hepatocytes, triggers STING and IL-6 release.", "protein": "cGAS", "protein_enriched": { "function": "Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:21478870, PubMed:23258413, PubMed:23707061, PubMed:", "gene_name": "CGAS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N884" }, "relationship_type": "causal", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "N-glycosylation required for proper trafficking and signaling.", "mechanism": "Activated by cGAS in macrophages, drives inflammatory cytokine production.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "causal", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Mallory-Denk body-associated chronic liver disease", "glycan_involvement": "N-glycosylation essential for secretion and activity.", "mechanism": "Released by macrophages upon cGAS-STING activation; mediates inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD)", "glycan_involvement": "Glycosylation of TGF-\u03b2 and receptors modulates axis activity.", "mechanism": "Pathologically activated in MASLD; inhibition suppresses MDB formation and inflammation.", "protein": "TGF-\u03b2/JNK axis", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131408" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects antibody recognition.", "mechanism": "Anti-PD-L1 antibodies delivered via hydrogels stimulate CD8+ T-cell activity and anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Aberrant O-glycosylation of MUC1 promotes immune evasion.", "mechanism": "Aptamer-decorated nanoparticles knock out MUC1, downregulate PD-L1, and increase pro-inflammatory cytokine secretion.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates HER2 stability and immune recognition.", "mechanism": "Peptide-conjugated photodynamic therapy degrades HER2, enhancing cytotoxic T-cell activity.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation affects CD44 ligand binding and signaling.", "mechanism": "CD44 regulates CAF-specific gene expression via TGF-\u03b2/Smads and NF-\u03baB pathways, promoting tumor progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may affect GPX4 localization and function.", "mechanism": "GPX4 protects against ferroptosis, influencing immune cell populations and anti-tumor responses.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12131435" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation regulates CD73 enzymatic activity.", "mechanism": "Macrophage-derived mimetic nanovesicles target CD73 to modulate immune checkpoints and enhance immunotherapy.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma", "glycan_involvement": "Glycosylation may regulate CST2 secretion and activity.", "mechanism": "CST2 is linked to proliferation and metastasis, suggesting its potential as a therapeutic target.", "protein": "CST2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Catalyzes galactosylation of glycoproteins, affecting cell-cell interactions.", "mechanism": "B4GALT3 regulates CAF transformation and TME remodeling.", "protein": "B4GALT3", "protein_enriched": { "function": "Plays a role with ILK in promoting the cell adhesion and spreading of leukocytes", "gene_name": "PARVG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HBI0" }, "relationship_type": "causal", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation influences HSP90\u03b1 secretion and stability.", "mechanism": "Extracellular HSP90\u03b1 expression correlates with prognosis and immunotherapy efficacy.", "protein": "HSP90\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12131435" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation modulates GRP78 cell surface expression.", "mechanism": "GRP78-targeted nanoparticles enhance ovarian cancer treatment.", "protein": "GRP78", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131435" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation modulates HLA-II stability and peptide presentation.", "mechanism": "HLA-II allelic variation shapes antigen presentation, influencing autoantibody specificity and disease risk.", "protein": "HLA-II proteins", "relationship_type": "causal", "source_pmcid": "PMC12131526" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "Glycosylation affects HLA-II surface expression and immune recognition.", "mechanism": "HLA-II alleles affect antibody specificity to allergens, influencing allergy susceptibility.", "protein": "HLA-II proteins", "relationship_type": "causal", "source_pmcid": "PMC12131526" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation impacts antigen presentation and immune evasion.", "mechanism": "HLA-II genotype influences antibody responses to tumor antigens.", "protein": "HLA-II proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "high", "disease": "Epstein-Barr Virus infection", "glycan_involvement": "Glycosylation may affect antigen processing and presentation.", "mechanism": "Antibody specificity to EBV nuclear antigen 1 is strongly associated with HLA-II alleles.", "protein": "EBV nuclear antigen 1", "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "Glycosylation may influence immunogenicity and antibody binding.", "mechanism": "Antibody responses to Streptolysin O are associated with specific HLA-II alleles.", "protein": "Streptolysin O", "protein_enriched": { "function": "Required for CpsD phosphorylation (By similarity). Involved in the regulation of capsular polysaccharide biosynthesis. May be part of a complex that directs the coordinated polymerization and export t", "gene_name": "cpsC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0T8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "medium", "disease": "Escherichia coli infection", "glycan_involvement": "Glycosylation may affect antigen processing.", "mechanism": "Antibody specificity to NlpD is linked to HLA-II genotype.", "protein": "Murein hydrolase activator NlpD", "protein_enriched": { "function": "DNA-dependent RNA polymerase (RNAP) catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates", "gene_name": "rpoC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A8T7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Antibody responses to Clumping factor B are associated with HLA-II alleles.", "protein": "Clumping factor B", "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Antibody specificity to Protein A is linked to HLA-II genotype.", "protein": "Protein A", "protein_enriched": { "function": "Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the ", "gene_name": "spa", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P38507" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation affects flagellum structure and immune recognition.", "mechanism": "Antibody responses to flagellum proteins are associated with HLA-II alleles and may be relevant in IBD.", "protein": "Flagellum proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12131526" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation of autoantigens modulates immune recognition and tolerance.", "mechanism": "Antibody specificity to autoantigens is shaped by HLA-II genotype, influencing disease severity.", "protein": "Autoantigens (various)", "relationship_type": "causal", "source_pmcid": "PMC12131526" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Not directly addressed; HMGCS1 may be glycosylated but not discussed in this study.", "mechanism": "High HMGCS1 expression predicts poor prognosis and reduced immunotherapy efficacy; associated with increased cholesterol biosynthesis and decreased CD8+ T cell infiltration.", "protein": "HMGCS1", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "high", "disease": "DLBCL", "glycan_involvement": "Not directly addressed.", "mechanism": "High HMGCS1 expression correlates with shorter overall survival, enriched in malignant B cells, and linked to cholesterol homeostasis and amino acid degradation.", "protein": "HMGCS1", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Overexpression of HMGCS1 accelerates tumor growth and metabolic reprogramming; knockdown suppresses tumor progression in mouse models treated with PD-1 antibody.", "protein": "HMGCS1", "relationship_type": "causal", "source_pmcid": "PMC12131551" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Knockdown of HMGCS1 enhances response to PD-1 immunotherapy and reduces tumor growth.", "protein": "HMGCS1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131551" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Not applicable.", "mechanism": "Higher plasma L-leucine levels are associated with better prognosis and increased T cell counts in NSCLC patients receiving immunotherapy.", "protein": "L-leucine", "relationship_type": "protective", "source_pmcid": "PMC12131551" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Part of BCAA-related gene signature predictive of prognosis and immunotherapy response.", "protein": "ACAT2", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Part of BCAA-related gene signature predictive of prognosis and immunotherapy response.", "protein": "ALDH2", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Part of BCAA-related gene signature predictive of prognosis and immunotherapy response.", "protein": "MLYCD", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Not discussed.", "mechanism": "Part of BCAA-related gene signature predictive of prognosis and immunotherapy response.", "protein": "PPM1K", "protein_enriched": { "function": "Serine/threonine-protein phosphatase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with BCKDK, serving as a metabolic regulatory node that coordinates branched", "gene_name": "PPM1K", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N3J5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Not discussed.", "mechanism": "High HMGCS1 expression predicts worse overall survival in melanoma patients treated with immunotherapy.", "protein": "HMGCS1", "relationship_type": "biomarker", "source_pmcid": "PMC12131551" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation at Asn162 with sialylation is essential for function.", "mechanism": "Promotes TNBC progression by enhancing glycolysis and lactate recycling via integrin \u03b16\u03b24-FAK-AKT-HIF-1\u03b1-MCT4 and integrin \u03b16\u03b24-CD44-MCT1 axes.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "causal", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Detection relies on sialylated N-glycan at Asn162.", "mechanism": "High SIA-IgG expression correlates with poor prognosis and shorter survival in TNBC patients.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Therapeutic antibody specifically recognizes sialylated N-glycan at Asn162.", "mechanism": "Targeting SIA-IgG with neutralizing antibody (RP215) inhibits TNBC growth and glycolytic activity in vivo.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131568" }, { "confidence": "medium", "disease": "Cancer stem cell-driven tumors", "glycan_involvement": "Sialylated N-glycan at Asn162 required for interaction.", "mechanism": "Promotes stemness and drug resistance in cancer stem cells via interaction with integrin \u03b16\u03b24 and CD44.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "causal", "source_pmcid": "PMC12131568" }, { "confidence": "medium", "disease": "Lung squamous cell carcinoma", "glycan_involvement": "Sialylated N-glycan at Asn162 mediates receptor binding.", "mechanism": "Promotes proliferation and invasion via integrin \u03b16\u03b24-FAK-AKT pathway; targeting SIA-IgG inhibits tumor growth.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131568" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Sialylation at Asn162 enables binding to immune inhibitory receptors.", "mechanism": "Promotes immune evasion by suppressing T-cell activity; targeting SIA-IgG restores immune response.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "CD44 is a glycoprotein; interaction with SIA-IgG depends on integrin \u03b24.", "mechanism": "CD44 mediates SIA-IgG-induced upregulation of MCT1, enhancing lactate reuse and glycolysis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Integrin \u03b16\u03b24 is a glycoprotein; SIA-IgG binding requires sialylated N-glycan.", "mechanism": "Acts as a receptor for SIA-IgG, initiating FAK-AKT-HIF-1\u03b1 signaling to promote glycolysis and invasion.", "protein": "Integrin \u03b16\u03b24", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Upregulation is downstream of SIA-IgG glycosylation-dependent signaling.", "mechanism": "Upregulated by SIA-IgG, these proteins drive glycolysis and lactate transport, supporting TNBC progression.", "protein": "HK2, LDHA, MCT1, MCT4", "relationship_type": "causal", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Breast cancer (general)", "glycan_involvement": "Sialylated N-glycan at Asn162 is diagnostic epitope.", "mechanism": "High expression in all breast cancer subtypes, especially TNBC, correlates with aggressive disease.", "protein": "Sialylated IgG (SIA-IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12131568" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Endoglin is a heavily glycosylated protein; glycosylation is essential for its cell surface expression and function.", "mechanism": "NOX4-dependent upregulation of endoglin restores angiogenic function in diabetic ECFCs.", "protein": "Endoglin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131569" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "SERPINE1 is glycosylated; glycosylation affects its stability and secretion.", "mechanism": "NOX4 overexpression increases SERPINE1, promoting angiogenesis and ECFC tube formation in diabetes.", "protein": "SERPINE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131569" }, { "confidence": "high", "disease": "Ischaemic cardiovascular disease", "glycan_involvement": "Glycosylation required for endoglin's pro-angiogenic activity.", "mechanism": "Endoglin supports vascular integrity and angiogenesis, mitigating ischaemic damage.", "protein": "Endoglin", "relationship_type": "protective", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Ischaemic cardiovascular disease", "glycan_involvement": "Glycosylation modulates SERPINE1's function in angiogenesis.", "mechanism": "SERPINE1 promotes extracellular matrix remodeling and angiogenesis, aiding tissue repair.", "protein": "SERPINE1", "relationship_type": "protective", "source_pmcid": "PMC12131569" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "NOX4 is not a glycoprotein; no direct glycan involvement.", "mechanism": "Reduced NOX4 expression in ECFCs leads to impaired angiogenesis in diabetes.", "protein": "NOX4", "relationship_type": "causal", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation status affects endoglin's biomarker utility.", "mechanism": "Endoglin levels correlate with ECFC angiogenic capacity and vascular health.", "protein": "Endoglin", "relationship_type": "biomarker", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "VEGFR2 is glycosylated; glycosylation influences receptor function.", "mechanism": "VEGFR2 phosphorylation status reflects angiogenic signaling in diabetic ECFCs.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "CD31 glycosylation is important for cell adhesion.", "mechanism": "CD31 expression marks ECFC identity and vascular health.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Ischaemic cardiovascular disease", "glycan_involvement": "Glycosylation critical for CD105 function.", "mechanism": "CD105 identifies ECFCs with angiogenic potential in CVD.", "protein": "CD105", "relationship_type": "biomarker", "source_pmcid": "PMC12131569" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation affects SERPINE1 secretion and activity.", "mechanism": "SERPINE1 levels reflect ECFC angiogenic and migratory capacity.", "protein": "SERPINE1", "relationship_type": "biomarker", "source_pmcid": "PMC12131569" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; glycosylation level correlates with disease severity.", "mechanism": "HbA1c reflects average blood glucose over prior 2-3 months; elevated in T2D.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "high", "disease": "Prediabetes", "glycan_involvement": "Glycation increases with impaired glucose metabolism.", "mechanism": "Intermediate HbA1c levels indicate prediabetes and risk of progression to T2D.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL particles are glycosylated, affecting clearance and atherogenicity.", "mechanism": "Elevated LDL-c is a risk factor for atherosclerosis in T2D.", "protein": "Low-density lipoprotein cholesterol (LDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation modulates HDL function and anti-inflammatory properties.", "mechanism": "Higher HDL-c is protective against cardiovascular complications in T2D.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "TG-rich lipoproteins are glycosylated, influencing metabolism.", "mechanism": "Elevated TG is common in T2D and prediabetes, contributing to metabolic syndrome.", "protein": "Triglycerides (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability and serum levels.", "mechanism": "Elevated AST may indicate liver injury, which is more common in T2D.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Glycosylation modulates enzyme activity and detection.", "mechanism": "Elevated ALT is a marker for non-alcoholic fatty liver disease in T2D.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Glycosylation influences enzyme secretion and activity.", "mechanism": "Elevated GGT is associated with hepatic steatosis and metabolic syndrome.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "high", "disease": "Impaired Fasting Glucose (IFG)", "glycan_involvement": "Reflects glycoprotein-mediated glucose transport and metabolism.", "mechanism": "Elevated FPG is diagnostic for IFG and prediabetes.", "protein": "Fasting plasma glucose (FPG)", "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus", "glycan_involvement": "Glycation level reflects maternal glucose status.", "mechanism": "HbA1c used to monitor glycemic control in gestational diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131578" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "N-glycosylation may regulate NLRP3 stability and activation (not directly studied here).", "mechanism": "NLRP3 activation in microglia and neurons drives neuroinflammation, neurodegeneration, and cognitive impairment in VaD; inhibition improves outcomes.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "Possible glycosylation affects ASC function (not directly studied).", "mechanism": "ASC is upregulated in VaD, promoting inflammasome assembly and caspase-1 activation; inhibition reduces neuroinflammation.", "protein": "ASC (PYCARD)", "protein_enriched": { "function": "Functions as a key mediator in apoptosis and inflammation (PubMed:11103777, PubMed:12646168, PubMed:15030775, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMe", "gene_name": "PYCARD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9ULZ3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "Possible glycosylation affects secretion/activation (not directly studied).", "mechanism": "Caspase-1 activation leads to IL-1\u03b2 maturation and neuroinflammation; inhibition is neuroprotective.", "protein": "Caspase-1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting secretion and stability.", "mechanism": "Elevated IL-1\u03b2 drives neuroinflammation, BBB disruption, and demyelination in VaD; reduction improves outcomes.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and activity.", "mechanism": "Elevated TNF-\u03b1 in VaD promotes neuroinflammation and neuronal death; reduction is protective.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "IL-4 glycosylation affects secretion and receptor interaction.", "mechanism": "IL-4 is reduced in VaD; restoration by AMS-17 promotes anti-inflammatory response and neuroprotection.", "protein": "Interleukin-4 (IL-4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "Occludin is glycosylated, affecting tight junction stability.", "mechanism": "Occludin downregulation leads to BBB disruption in VaD; AMS-17 restores occludin, improving BBB integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131594" }, { "confidence": "high", "disease": "Vascular dementia (VaD)", "glycan_involvement": "Claudin-5 glycosylation modulates tight junction assembly.", "mechanism": "Claudin-5 loss disrupts BBB in VaD; AMS-17 restores claudin-5, protecting BBB.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12131594" }, { "confidence": "medium", "disease": "Vascular dementia (VaD)", "glycan_involvement": "Fibrinogen glycosylation affects its deposition and interaction with microglia.", "mechanism": "Fibrinogen deposition in brain activates microglial NLRP3 inflammasome, contributing to BBB dysfunction and neuroinflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12131594" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "N-glycosylation may regulate NLRP3 activation (not directly studied here).", "mechanism": "NLRP3 activation by amyloid-\u03b2 promotes neuroinflammation and progression of AD.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12131594" }, { "confidence": "medium", "disease": "Surgical Site Infection (SSI)", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect its stability and function, but not directly discussed in SSI context.", "mechanism": "Serum albumin level is used as a marker of nutritional and inflammatory status, which may influence SSI risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131625" }, { "confidence": "low", "disease": "Malignant Tumor", "glycan_involvement": "Glycosylation state may change in cancer, but not directly addressed.", "mechanism": "Lower serum albumin may reflect poor nutritional status in malignancy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131625" }, { "confidence": "low", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycation (not glycosylation) of albumin is relevant in diabetes.", "mechanism": "Albumin levels may be altered in diabetes, affecting wound healing and infection risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131625" }, { "confidence": "low", "disease": "Inflammatory Disease", "glycan_involvement": "Glycosylation may modulate albumin's half-life and function.", "mechanism": "Albumin is a negative acute-phase reactant; levels decrease in inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131625" }, { "confidence": "low", "disease": "Delayed Wound Healing", "glycan_involvement": "Glycosylation may affect albumin's transport and stability.", "mechanism": "Low albumin is associated with impaired wound healing.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131625" }, { "confidence": "high", "disease": "Desulfovibrio desulfuricans bacteraemia", "glycan_involvement": "Glycosylation affects CRP stability and function.", "mechanism": "CRP is elevated in response to infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Glycosylation modulates troponin clearance.", "mechanism": "Elevated troponin indicates cardiac injury during septic shock.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "medium", "disease": "Multiorgan failure", "glycan_involvement": "Glycosylation influences albumin half-life.", "mechanism": "Low albumin reflects poor liver function and systemic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "medium", "disease": "Hepatic disturbances", "glycan_involvement": "Glycosylation affects ALP activity and secretion.", "mechanism": "Elevated ALP indicates cholestasis or liver dysfunction.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "medium", "disease": "Hepatic disturbances", "glycan_involvement": "Glycosylation modulates GGT stability.", "mechanism": "Elevated GGT is a marker of hepatobiliary disease.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "low", "disease": "Hepatic disturbances", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated AST reflects liver cell injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "low", "disease": "Hepatic disturbances", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated ALT is a marker of hepatocellular injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131628" }, { "confidence": "low", "disease": "Intracardiac thrombus", "glycan_involvement": "Glycosylation influences valve structure and thrombogenicity.", "mechanism": "Altered glycoprotein composition may affect thrombus formation.", "protein": "Mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12131628" }, { "confidence": "low", "disease": "Intracardiac thrombus", "glycan_involvement": "Glycosylation modulates valve surface properties.", "mechanism": "Valve glycoproteins may contribute to thrombus attachment.", "protein": "Aortic valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12131628" }, { "confidence": "medium", "disease": "Desulfovibrio desulfuricans bacteraemia", "glycan_involvement": "Fc glycosylation affects IgG effector functions.", "mechanism": "IgG mediates immune response against bacterial infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12131628" }, { "confidence": "high", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Elevated PTX3 reflects innate immune activation and correlates with severity and mortality.", "protein": "PTX3 (Pentraxin 3)", "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "high", "disease": "Severe Leptospirosis", "glycan_involvement": "O-glycosylation may affect stability and plasma half-life.", "mechanism": "High copeptin levels indicate AVP system activation and correlate with disease severity.", "protein": "Copeptin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "high", "disease": "Severe Leptospirosis", "glycan_involvement": "Extensive N- and O-glycosylation modulates multimerization and function.", "mechanism": "Elevated VWF indicates endothelial activation/damage and is associated with severe outcomes.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "medium", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation critical for ligand binding and cell adhesion.", "mechanism": "Elevated sE-selectin reflects endothelial activation and correlates with severity.", "protein": "E-selectin (sE-selectin)", "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "medium", "disease": "Leptospirosis Pulmonary Haemorrhage Syndrome (SPHS)", "glycan_involvement": "N-glycosylation modulates cell-cell interactions.", "mechanism": "Elevated ICAM-1 linked to pulmonary involvement and organ dysfunction.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "O-glycosylation and heparan sulfate chains essential for function.", "mechanism": "Elevated Syndecan-1 reflects endothelial glycocalyx shedding and correlates with renal dysfunction.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "high", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "High Angiopoietin-2 levels predict severe disease, AKI, and need for intensive care.", "protein": "Angiopoietin-2", "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "medium", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation affects iron binding and plasma half-life.", "mechanism": "Reduced transferrin levels associated with severe disease and altered iron metabolism.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "medium", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation modulates hemoglobin binding and clearance.", "mechanism": "Elevated haptoglobin reflects acute phase response and correlates with severity.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "medium", "disease": "Severe Leptospirosis", "glycan_involvement": "N-glycosylation influences lipid binding and anti-inflammatory properties.", "mechanism": "Reduced APOA-I levels associated with severe disease and altered lipid metabolism.", "protein": "Apolipoprotein A-I", "relationship_type": "biomarker", "source_pmcid": "PMC12131637" }, { "confidence": "high", "disease": "Bovine coronavirus infection", "glycan_involvement": "C3 is a heavily glycosylated protein; glycosylation is essential for its stability and function in complement activation.", "mechanism": "BCoV infection downregulates C3 mRNA and protein at late stages, suppressing complement-mediated antiviral defense.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "medium", "disease": "Bovine coronavirus infection", "glycan_involvement": "C4 glycosylation is required for secretion and activity.", "mechanism": "BCoV infection leads to decreased C4 expression, impairing classical complement pathway activation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "medium", "disease": "Bovine coronavirus infection", "glycan_involvement": "CFB glycosylation affects its proteolytic activation.", "mechanism": "CFB downregulation by BCoV impairs alternative complement pathway, reducing innate immunity.", "protein": "Complement Factor B (CFB)", "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "medium", "disease": "Bovine coronavirus infection", "glycan_involvement": "A2M glycosylation modulates its inhibitory activity.", "mechanism": "A2M upregulation may act as a broad-spectrum protease inhibitor, limiting tissue damage during infection.", "protein": "Alpha-2-macroglobulin (A2M)", "relationship_type": "protective", "source_pmcid": "PMC12131655" }, { "confidence": "low", "disease": "Bovine coronavirus infection", "glycan_involvement": "Glycosylation affects SERPINF1 secretion and function.", "mechanism": "SERPINF1 is downregulated during BCoV infection, possibly reflecting altered cell survival/apoptosis.", "protein": "Serpin family F member 1 (SERPINF1)", "relationship_type": "biomarker", "source_pmcid": "PMC12131655" }, { "confidence": "low", "disease": "Bovine coronavirus infection", "glycan_involvement": "Glycosylation is important for vitronectin's interaction with complement components.", "mechanism": "Vitronectin downregulation may impair complement regulation and tissue repair during infection.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "low", "disease": "Bovine coronavirus infection", "glycan_involvement": "Glycosylation is required for C1INH stability and inhibitory function.", "mechanism": "C1INH downregulation may lead to uncontrolled complement activation and inflammation.", "protein": "C1 inhibitor (C1INH)", "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "low", "disease": "Bovine coronavirus infection", "glycan_involvement": "C9 glycosylation is important for MAC assembly.", "mechanism": "C9 downregulation reduces membrane attack complex formation, limiting viral lysis.", "protein": "Complement C9", "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "low", "disease": "Bovine coronavirus infection", "glycan_involvement": "Glycosylation may affect ESRP1 localization and function.", "mechanism": "ESRP1 upregulation may reflect epithelial cell response to infection.", "protein": "Epithelial splicing regulatory protein 1 (ESRP1)", "protein_enriched": { "function": "Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, bein", "gene_name": "CRTC1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G61926JM" ], "uniprot_id": "Q6UUV9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131655" }, { "confidence": "high", "disease": "Immune evasion", "glycan_involvement": "Glycosylation is essential for C3's immune function.", "mechanism": "BCoV suppresses C3 to evade complement-mediated clearance.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12131655" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and function.", "mechanism": "Elevated CRP indicates increased inflammation in SCAP, especially in MP-infected children.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "Procalcitonin is glycosylated, influencing its secretion and activity.", "mechanism": "Higher PCT levels correlate with severity and inflammation in SCAP, especially MP infection.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "LDH glycosylation modulates enzyme stability.", "mechanism": "Elevated LDH reflects tissue damage and inflammation, especially in MP-infected SCAP.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects clearance.", "mechanism": "High D-dimer is associated with severe inflammation and coagulopathy in SCAP.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "HBP glycosylation modulates its interaction with heparin and endothelium.", "mechanism": "Elevated HBP promotes inflammation and vascular permeability in SCAP.", "protein": "Heparin-binding protein", "protein_enriched": { "function": "Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. Signals through CCR2B and CCR3 receptors. Plays a role in the accumulation of leukocytes at bot", "gene_name": "CCL13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99616" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131815" }, { "confidence": "medium", "disease": "Haemophilus influenzae pneumonia", "glycan_involvement": "Albumin glycosylation affects antioxidant and transport functions.", "mechanism": "Higher albumin correlates with HI infection and less severe inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12131815" }, { "confidence": "medium", "disease": "Streptococcus pneumoniae pneumonia", "glycan_involvement": "Bacterial glycoproteins may modulate host immune response.", "mechanism": "Higher abundance suppresses inflammation via NF-\u03baB pathway inhibition.", "protein": "Rothia mucilaginosa", "relationship_type": "protective", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Severe community-acquired pneumonia (SCAP)", "glycan_involvement": "Capsular polysaccharide and glycoproteins are key for virulence.", "mechanism": "SP surface glycoproteins mediate adhesion and immune evasion, causing SCAP.", "protein": "Streptococcus pneumoniae", "relationship_type": "causal", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Refractory Mycoplasma pneumoniae pneumonia (RMPP)", "glycan_involvement": "Adhesin glycoproteins interact with host glycans for colonization.", "mechanism": "MP adhesin glycoproteins trigger intense inflammation and persistent fever.", "protein": "Mycoplasma pneumoniae", "relationship_type": "causal", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Haemophilus influenzae pneumonia", "glycan_involvement": "Surface glycoproteins bind host glycan receptors.", "mechanism": "HI glycoprotein adhesins facilitate airway colonization and infection.", "protein": "Haemophilus influenzae", "relationship_type": "causal", "source_pmcid": "PMC12131815" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation is essential for ABCB1 folding and membrane localization.", "mechanism": "ABCB1 mediates edoxaban efflux, potentially affecting drug levels in AF patients.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "Glycosylation affects CYP3A5 stability and activity.", "mechanism": "CYP3A5 metabolizes edoxaban, influencing drug clearance in AF therapy.", "protein": "Cytochrome P450 3A5 (CYP3A5)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen ", "gene_name": "CYP3A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20815" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "FXa is N-glycosylated, which modulates its secretion and activity.", "mechanism": "FXa activity drives thrombus formation in AF; edoxaban inhibits FXa.", "protein": "Coagulation Factor X (FXa)", "relationship_type": "causal", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Cardioembolic infarction", "glycan_involvement": "Glycosylation required for ABCB1 function.", "mechanism": "ABCB1 influences edoxaban pharmacokinetics, impacting prevention of infarction.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Deep vein thrombosis", "glycan_involvement": "Glycosylation critical for transporter activity.", "mechanism": "ABCB1 affects edoxaban bioavailability in DVT prevention.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation maintains ABCB1 structure and function.", "mechanism": "ABCB1 modulates edoxaban levels for embolism prophylaxis.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Cardioembolic infarction", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "CYP3A5 metabolizes edoxaban, affecting its efficacy in infarction prevention.", "protein": "Cytochrome P450 3A5 (CYP3A5)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen ", "gene_name": "CYP3A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20815" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Deep vein thrombosis", "glycan_involvement": "Glycosylation affects CYP3A5 function.", "mechanism": "CYP3A5 impacts edoxaban metabolism in DVT therapy.", "protein": "Cytochrome P450 3A5 (CYP3A5)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen ", "gene_name": "CYP3A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20815" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation required for proper enzyme activity.", "mechanism": "CYP3A5 modulates edoxaban clearance in embolism treatment.", "protein": "Cytochrome P450 3A5 (CYP3A5)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen ", "gene_name": "CYP3A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20815" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "Cardioembolic infarction", "glycan_involvement": "N-glycosylation regulates FXa secretion and activity.", "mechanism": "FXa drives clot formation; edoxaban inhibits FXa to prevent infarction.", "protein": "Coagulation Factor X (FXa)", "relationship_type": "causal", "source_pmcid": "PMC12131839" }, { "confidence": "high", "disease": "In-hospital cardiac arrest (IHCA)", "glycan_involvement": "NSE is a glycoprotein; glycosylation may affect its stability and serum detectability.", "mechanism": "NSE levels reflect neuronal injury after cardiac arrest and predict poor prognosis.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131872" }, { "confidence": "high", "disease": "In-hospital cardiac arrest (IHCA)", "glycan_involvement": "S100B is a glycoprotein; glycosylation may influence its clearance and immunoreactivity.", "mechanism": "S100B is released after brain injury and correlates with neurological outcome post-arrest.", "protein": "S100B protein", "relationship_type": "biomarker", "source_pmcid": "PMC12131872" }, { "confidence": "high", "disease": "In-hospital cardiac arrest (IHCA)", "glycan_involvement": "CRP is N-glycosylated; glycosylation modulates its function and half-life.", "mechanism": "hsCRP indicates systemic inflammation and is associated with worse outcomes after cardiac arrest.", "protein": "High-sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12131872" }, { "confidence": "medium", "disease": "In-hospital cardiac arrest (IHCA)", "glycan_involvement": "Endothelin-1 is glycosylated; glycosylation affects receptor binding and bioactivity.", "mechanism": "Elevated endothelin-1 reflects endothelial dysfunction and predicts poor prognosis.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "biomarker", "source_pmcid": "PMC12131872" }, { "confidence": "high", "disease": "Systemic inflammatory response", "glycan_involvement": "Glycosylation state influences CRP's interaction with immune cells.", "mechanism": "hsCRP is an acute-phase reactant elevated in systemic inflammation post-cardiac arrest.", "protein": "High-sensitivity C-reactive protein (hsCRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12131872" }, { "confidence": "medium", "disease": "Sleep-related epilepsies (SRE)", "glycan_involvement": "Glycosylation of myelin proteins is essential for myelin sheath integrity and neuroprotection.", "mechanism": "Myelin glycoprotein in the mature outer myelin sheath alleviates neuroexcitotoxicity from abnormal neuronal discharge, protecting axons and nerve fibers.", "protein": "Myelin glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12132067" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation is required for proper function and stability of myelin glycoproteins.", "mechanism": "Myelin glycoprotein helps maintain axonal integrity and limits white matter damage during epileptic activity.", "protein": "Myelin glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC12132067" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "SREBP-1c is a glycoprotein; glycosylation may affect stability and activity, but not directly discussed.", "mechanism": "Upregulation promotes fatty acid synthesis and lipid accumulation in liver; downregulation by SIL-SOR-MPs reduces steatosis.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "FAS is glycosylated, which may influence its enzymatic activity; not directly discussed.", "mechanism": "Upregulation increases lipid synthesis; downregulation by SIL-SOR-MPs reduces hepatic lipid accumulation.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ACC1 is glycosylated; glycosylation may affect function, not directly discussed.", "mechanism": "Promotes fatty acid synthesis; downregulation by SIL-SOR-MPs reduces steatosis.", "protein": "ACC1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "PPAR-\u03b1 is glycosylated; glycosylation may modulate receptor activity, not directly discussed.", "mechanism": "Activation promotes fatty acid oxidation, reducing hepatic lipid accumulation; upregulated by SIL-SOR-MPs.", "protein": "PPAR-\u03b1", "protein_enriched": { "function": "Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethano", "gene_name": "PPARA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07869" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "PPAR-\u03b3 is glycosylated; glycosylation may affect function, not directly discussed.", "mechanism": "Activation promotes lipid metabolism and insulin sensitivity; upregulated by SIL-SOR-MPs.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CPT1\u03b1 is glycosylated; glycosylation may affect mitochondrial targeting, not directly discussed.", "mechanism": "Key enzyme in fatty acid \u03b2-oxidation; upregulation by SIL-SOR-MPs enhances lipid catabolism.", "protein": "CPT1\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "ACOX1 is glycosylated; glycosylation may affect peroxisomal localization, not directly discussed.", "mechanism": "Catalyzes first step in peroxisomal fatty acid \u03b2-oxidation; upregulated by SIL-SOR-MPs.", "protein": "ACOX1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132069" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may affect SREBP-1c processing, not directly discussed.", "mechanism": "Overexpression drives progression from steatosis to steatohepatitis via increased lipogenesis.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132069" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may modulate receptor function, not directly discussed.", "mechanism": "Activation reduces inflammation and fibrosis by promoting fatty acid oxidation.", "protein": "PPAR-\u03b1", "protein_enriched": { "function": "Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethano", "gene_name": "PPARA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07869" }, "relationship_type": "protective", "source_pmcid": "PMC12132069" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect SREBP-1c stability, not directly discussed.", "mechanism": "Chronic upregulation contributes to carcinogenesis via persistent lipid accumulation and metabolic dysregulation.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12132069" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Claudin5 is a glycoprotein; glycosylation may affect junction stability.", "mechanism": "Claudin5 rearrangement and upregulation linked to BBB remodeling after blood flow cessation.", "protein": "Claudin5", "protein_enriched": { "function": "", "gene_name": "Nrxn2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O88723" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "high", "disease": "Microvascular instability", "glycan_involvement": "Vitronectin glycosylation is important for ECM interactions.", "mechanism": "Vitronectin downregulation leads to ECM destabilization and pericyte detachment.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates PECAM-1 adhesive function.", "mechanism": "PECAM-1 upregulation marks endothelial activation and leukocyte transmigration.", "protein": "PECAM-1 (CD31)", "relationship_type": "biomarker", "source_pmcid": "PMC12132235" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for ligand binding.", "mechanism": "E-selectin upregulation facilitates leukocyte recruitment during vascular inflammation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132235" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects VCAM-1 function.", "mechanism": "VCAM-1 upregulation promotes leukocyte adhesion and transmigration.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132235" }, { "confidence": "high", "disease": "Capillary constriction", "glycan_involvement": "ET-1 is glycosylated; glycosylation may affect secretion and receptor binding.", "mechanism": "ET-1 upregulation drives pericyte-mediated capillary constriction after blood flow cessation.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "medium", "disease": "Microvascular instability", "glycan_involvement": "Integrin glycosylation modulates ECM binding.", "mechanism": "Upregulation may compensate for reduced vitronectin, supporting vessel integrity.", "protein": "Integrin alpha-5", "relationship_type": "protective", "source_pmcid": "PMC12132235" }, { "confidence": "medium", "disease": "Pericyte loss", "glycan_involvement": "MMP9 glycosylation affects secretion and activity.", "mechanism": "MMP9 upregulation promotes ECM degradation, facilitating pericyte detachment.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "medium", "disease": "No-reflow phenomenon", "glycan_involvement": "Glycosylation may affect Claudin5 localization and function.", "mechanism": "Claudin5 junction remodeling may limit capillary re-expansion after ischemia.", "protein": "Claudin5", "protein_enriched": { "function": "", "gene_name": "Nrxn2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O88723" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation critical for ECM integration.", "mechanism": "Vitronectin loss implicated in pericyte detachment in diabetic microvasculature.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "causal", "source_pmcid": "PMC12132235" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APOE stability and receptor interactions.", "mechanism": "APOE glycoprotein mediates cholesterol transport; APOE4 variant impairs lipid clearance, leading to astrocytic overload and metabolic breakdown.", "protein": "APOE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates secretion and stability.", "mechanism": "CHI3L1 (YKL-40) is upregulated in astrogliosis and correlates with tau pathology and hippocampal atrophy.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heavy N- and O-glycosylation regulates ligand binding and cell signaling.", "mechanism": "CD44 upregulation marks neuroinflammation and impaired astrocyte-neuron metabolic support.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may affect filament assembly and stability.", "mechanism": "GFAP elevation indicates astrocyte activation and metabolic stress.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for cell adhesion and signaling.", "mechanism": "CNTN2 correlates with metabolic stress and astrocyte-neuron signaling disruption.", "protein": "CNTN2", "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Vascular dysfunction/White matter hyperintensity", "glycan_involvement": "N-glycosylation affects ALB stability and transport.", "mechanism": "ALB levels in CSF/plasma correlate with vascular integrity and BBB disruption.", "protein": "ALB", "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates lipid binding.", "mechanism": "APOA4 participates in HDL formation and cholesterol efflux; altered levels reflect impaired lipid clearance.", "protein": "APOA4", "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects lipoprotein interactions.", "mechanism": "APOC1 is part of HDL particles; altered levels indicate disrupted cholesterol transport.", "protein": "APOC1", "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates function.", "mechanism": "APOC2 is involved in lipid metabolism; changes reflect impaired glial lipid handling.", "protein": "APOC2", "protein_enriched": { "function": "Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an ", "gene_name": "APOC2", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "P02655" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "PGLYRP2 is associated with complement activation and neuroinflammation.", "protein": "PGLYRP2", "protein_enriched": { "function": "May play a scavenger role by digesting biologically active peptidoglycan (PGN) into biologically inactive fragments. Has no direct bacteriolytic activity", "gene_name": "PGLYRP2", "glycan_count": 57, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G49108TO", "G29068FM", "G57321FI", "G53434XO", "G00273SJ", "G00912UN", "G01485JJ", "G04854VP", "G05933EN", "G06356OH", "G08290VR", "G08918WF", "G10486CT", "G10846ZT", "G14972EH", "G26330YA", "G27915IV", "G28681TP", "G31986NC", "G37412TK", "G37692EO", "G40574BA", "G40926MX", "G42358LZ", "G43223CG", "G45395BF", "G47737VJ", "G48414YA", "G49906RN", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G70619PT", "G72197KC", "G72747WU", "G82443XX", "G82830MN", "G84862VB", "G85269DF", "G94470IW", "G95865ZB", "G11911BT", "G22572EH", "G70232NH", "G75983OB", "G93683YO", "G74722FL", "G12341GU", "G20528HD", "G27058EU", "G40834TG", "G54010QB", "G59324HL", "G77669RF", "G89045VA" ], "uniprot_id": "Q96PD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132299" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation modulates PD-1 stability and ligand binding", "mechanism": "PD-1 blockade enhances anti-tumor immunity in HCC", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132512" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation regulates PD-L1 expression and immune recognition", "mechanism": "PD-L1 blockade prevents immune evasion by tumor cells", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132512" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation affects CTLA-4 surface expression", "mechanism": "CTLA-4 inhibition boosts T cell activation against HCC", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132512" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum detection", "mechanism": "Elevated AFP indicates higher tumor burden and poor prognosis", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12132512" }, { "confidence": "medium", "disease": "Immune resistance", "glycan_involvement": "IL-10 glycosylation modulates cytokine stability and receptor interaction", "mechanism": "IL-10 suppresses CD4+ and CD8+ T cell activity, promoting tumor growth", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "causal", "source_pmcid": "PMC12132512" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Albumin glycosylation status may influence its serum half-life", "mechanism": "Albumin levels reflect liver function and prognosis in HCC", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132512" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Surface glycoproteins mediate MDSC immunosuppressive functions", "mechanism": "MDSCs inhibit T cell and NK cell activity, promoting immune suppression and tumor progression", "protein": "MDSC-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12132512" }, { "confidence": "medium", "disease": "Immune resistance", "glycan_involvement": "Glycosylation of Treg surface proteins modulates immune interactions", "mechanism": "Treg cells suppress anti-tumor immunity, contributing to ICI resistance", "protein": "Treg-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12132512" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "PD-L1 glycosylation enhances immune evasion in portal hypertension context", "mechanism": "Splenomegaly (often due to portal hypertension) correlates with increased PD-L1 expression and immune suppression", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12132512" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "AFP glycosylation affects its diagnostic accuracy in liver disease", "mechanism": "Elevated AFP may reflect liver dysfunction associated with portal hypertension", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12132512" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "EP is a glycoprotein; glycosylation may affect its stability and localization.", "mechanism": "EP inhibition reduces protein digestion, increases fecal protein excretion, and induces weight loss in obese mice.", "protein": "Enteropeptidase (EP)", "protein_enriched": { "function": "Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation ", "gene_name": "BHMT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q93088" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132930" }, { "confidence": "high", "disease": "Congenital Enteropeptidase Deficiency", "glycan_involvement": "Glycosylation may affect EP function and deficiency phenotype.", "mechanism": "Deficiency leads to impaired protein digestion and a lean phenotype.", "protein": "Enteropeptidase (EP)", "protein_enriched": { "function": "Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation ", "gene_name": "BHMT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q93088" }, "relationship_type": "causal", "source_pmcid": "PMC12132930" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "CCK1R is glycosylated, which may affect receptor signaling and trafficking.", "mechanism": "CCK1R mediates satiety and food intake suppression; its activation contributes to weight loss.", "protein": "CCK1 receptor (CCK1R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132930" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "CCK is O-glycosylated, influencing hormone stability and receptor interaction.", "mechanism": "CCK release suppresses appetite and delays gastric emptying via CCK1R.", "protein": "Cholecystokinin (CCK)", "relationship_type": "protective", "source_pmcid": "PMC12132930" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Trypsin is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Trypsin inhibition (via EP/T inhibitors) reduces protein absorption, contributing to weight loss.", "protein": "Trypsin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132930" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "FGF21 is glycosylated, affecting secretion and activity.", "mechanism": "EP inhibition increases plasma FGF21, associated with improved metabolic control.", "protein": "Fibroblast Growth Factor 21 (FGF21)", "relationship_type": "biomarker", "source_pmcid": "PMC12132930" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)/Steatosis", "glycan_involvement": "Glycosylation may affect CCK1R function in hepatic signaling.", "mechanism": "CCK1R signaling modulates liver fat content; EP/T inhibition reduces steatosis independent of CCK1R.", "protein": "CCK1 receptor (CCK1R)", "relationship_type": "protective", "source_pmcid": "PMC12132930" }, { "confidence": "low", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation may modulate EP's interaction with gut mucosa.", "mechanism": "EP inhibition alters gut microbiota and fecal protein content, impacting inflammation.", "protein": "Enteropeptidase (EP)", "protein_enriched": { "function": "Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation ", "gene_name": "BHMT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q93088" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132930" }, { "confidence": "low", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "O-glycosylation affects CCK hormone stability.", "mechanism": "CCK release improves satiety and may indirectly improve glycemic control.", "protein": "Cholecystokinin (CCK)", "relationship_type": "protective", "source_pmcid": "PMC12132930" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect zymogen activation.", "mechanism": "Downstream activation by EP; inhibition reduces protein digestion and absorption.", "protein": "Chymotrypsinogen", "protein_enriched": { "function": "", "gene_name": "CTRB1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17538" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12132930" }, { "confidence": "high", "disease": "Salivary gland dysfunction", "glycan_involvement": "Mucin's protective function depends on O-glycosylation; reduction affects glycan-mediated hydration.", "mechanism": "BNZ administration reduces mucin secretion, impairing lubrication and hydration of oral surfaces.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12132995" }, { "confidence": "high", "disease": "Xerostomia (dry mouth)", "glycan_involvement": "O-glycosylation is essential for mucin's water retention and viscoelasticity.", "mechanism": "Reduced mucin leads to decreased oral surface hydration, contributing to dry mouth symptoms.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Salivary gland dysfunction", "glycan_involvement": "Amylase is glycosylated; glycan moieties may affect stability and secretion.", "mechanism": "BNZ exposure decreases amylase secretion, impairing digestive and protective functions of saliva.", "protein": "Amylase", "relationship_type": "causal", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Salivary gland dysfunction", "glycan_involvement": "Includes glycoproteins; glycosylation status may affect protein stability and function.", "mechanism": "Reduced total protein levels in saliva indicate glandular damage and impaired secretion.", "protein": "Total salivary proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Oral inflammation", "glycan_involvement": "O-glycans mediate mucin's anti-inflammatory barrier function.", "mechanism": "Mucin normally protects oral surfaces from inflammation; reduction increases susceptibility.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Chagas disease", "glycan_involvement": "Changes in glycosylation may affect mucin's biomarker potential.", "mechanism": "Altered mucin levels may reflect BNZ-induced side effects during Chagas disease treatment.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12132995" }, { "confidence": "low", "disease": "Oral inflammation", "glycan_involvement": "Glycosylation may influence amylase's interaction with oral bacteria.", "mechanism": "Amylase helps control oral microbiota; reduction may promote inflammation.", "protein": "Amylase", "relationship_type": "protective", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Oral inflammation", "glycan_involvement": "Loss of O-glycans impairs mucin's barrier function.", "mechanism": "Reduced mucin due to BNZ increases risk of oral inflammation.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12132995" }, { "confidence": "low", "disease": "Xerostomia (dry mouth)", "glycan_involvement": "Glycoprotein reduction contributes to decreased saliva viscosity.", "mechanism": "Lower total protein in saliva correlates with dry mouth symptoms.", "protein": "Total salivary proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12132995" }, { "confidence": "medium", "disease": "Salivary gland dysfunction", "glycan_involvement": "O-glycosylation status may enhance biomarker specificity.", "mechanism": "Mucin reduction is a sensitive indicator of BNZ-induced glandular dysfunction.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12132995" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "P-gp mediates rivaroxaban transport, affecting drug levels in VTE management.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects membrane localization and activity.", "mechanism": "BCRP transports rivaroxaban and TKIs, influencing drug resistance in cancer therapy.", "protein": "Breast Cancer Resistance Protein (BCRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "high", "disease": "Bleeding", "glycan_involvement": "Glycosylation stabilizes enzyme structure.", "mechanism": "Inhibition of CYP3A4 by TKIs (avitinib, gefitinib) reduces rivaroxaban metabolism, increasing bleeding risk.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "causal", "source_pmcid": "PMC12133000" }, { "confidence": "high", "disease": "Bleeding", "glycan_involvement": "Glycosylation supports enzyme activity.", "mechanism": "Gefitinib inhibits CYP2D6, decreasing rivaroxaban clearance and elevating bleeding risk.", "protein": "CYP2D6", "protein_enriched": { "function": "", "gene_name": "10A19I.15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV1" }, "relationship_type": "causal", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for enzyme function.", "mechanism": "CYP2J2 metabolizes rivaroxaban; inhibition by TKIs may alter anticoagulant efficacy, affecting thrombosis risk.", "protein": "CYP2J2", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). Mechanistically, uses molecular oxygen ", "gene_name": "CYP2J2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51589" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Bleeding", "glycan_involvement": "Glycosylation affects transporter efficiency.", "mechanism": "ABCB1 gene polymorphisms correlate with rivaroxaban plasma levels and bleeding risk.", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates substrate specificity.", "mechanism": "ABCG2 mediates drug resistance and influences rivaroxaban pharmacokinetics in cancer patients.", "protein": "ABCG2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation essential for transporter function.", "mechanism": "P-gp affects TKI and rivaroxaban transport in NSCLC patients, impacting drug efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation maintains enzyme stability.", "mechanism": "CYP3A4 metabolizes TKIs and rivaroxaban, influencing drug interactions in cancer therapy.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation required for proper enzyme activity.", "mechanism": "CYP2D6 metabolizes gefitinib and rivaroxaban, affecting drug levels in NSCLC treatment.", "protein": "CYP2D6", "protein_enriched": { "function": "", "gene_name": "10A19I.15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133000" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns (e.g., increased fucosylation) are associated with HCC.", "mechanism": "Serum AFP levels are used for HCC screening and risk prediction; elevated AFP is associated with HCC development.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133121" }, { "confidence": "medium", "disease": "Chronic hepatitis C", "glycan_involvement": "Glycosylation status may affect AFP's diagnostic specificity.", "mechanism": "AFP is sometimes elevated in chronic HCV infection, but less specific than for HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133121" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis may affect AFP levels.", "mechanism": "AFP can be mildly elevated in cirrhosis, but high levels are more indicative of HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133121" }, { "confidence": "medium", "disease": "Tricuspid Regurgitation", "glycan_involvement": "Valve glycoproteins maintain structural integrity; disruption alters glycosylation and function.", "mechanism": "Tumor impaction and removal disrupts glycoprotein-rich valve structure, leading to regurgitation.", "protein": "Tricuspid Valve Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133208" }, { "confidence": "medium", "disease": "Intravenous Leiomyomatosis (IVL)", "glycan_involvement": "Altered endothelial glycosylation may promote tumor adhesion and invasion.", "mechanism": "IVL invades venous endothelium, interacting with endothelial glycoproteins to facilitate intravascular growth.", "protein": "Endothelial Cell Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133208" }, { "confidence": "medium", "disease": "Coagulation Abnormalities", "glycan_involvement": "Platelet glycoprotein glycosylation affects aggregation and hemostasis.", "mechanism": "Platelet count reduction and transfusion indicate altered platelet glycoprotein function in IVL.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "medium", "disease": "Coagulation Abnormalities", "glycan_involvement": "Glycosylation modulates factor stability and activity.", "mechanism": "Prolonged PT-INR/APTT reflect dysfunction of glycosylated coagulation factors.", "protein": "Coagulation Factor Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "low", "disease": "Laryngeal Edema", "glycan_involvement": "Glycosylation regulates immunoglobulin-mediated inflammation.", "mechanism": "Immunoglobulin glycoproteins may modulate inflammatory response postoperatively.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC12133208" }, { "confidence": "low", "disease": "Hepatic Dysfunction", "glycan_involvement": "Altered glycosylation in liver disease affects transferrin isoforms.", "mechanism": "Transferrin levels may reflect hepatic synthetic function in IVL patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "low", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation status changes in hepatic dysfunction.", "mechanism": "Albumin glycoprotein levels indicate liver synthetic capacity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "medium", "disease": "Coagulation Abnormalities", "glycan_involvement": "Glycosylation affects fibrinogen polymerization and clot formation.", "mechanism": "Fibrinogen transfusion used to correct bleeding risk in IVL surgery.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "low", "disease": "Coagulation Abnormalities", "glycan_involvement": "Glycosylation modulates vWF activity and platelet binding.", "mechanism": "Potential involvement in abnormal bleeding and platelet function during IVL surgery.", "protein": "Von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12133208" }, { "confidence": "medium", "disease": "Intravenous Leiomyomatosis (IVL)", "glycan_involvement": "Aberrant glycosylation promotes tumor invasiveness and immune evasion.", "mechanism": "Tumor cell glycoproteins mediate adhesion to endothelium and intravascular extension.", "protein": "Tumor Cell Surface Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133208" }, { "confidence": "high", "disease": "Amoxicillin clavulanate-induced liver injury (AC-DILI)", "glycan_involvement": "ERAP2 is a glycoprotein; glycosylation may affect its stability and function in antigen processing.", "mechanism": "ERAP2 rs1363907 mutation alters peptide trimming, affecting antigen presentation and increasing susceptibility to AC-DILI.", "protein": "ERAP2 (Endoplasmic Reticulum Aminopeptidase 2)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP2", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G45526EA", "G62765YT", "G72747WU", "G80920RR", "G90575OW", "G92135MA", "G95177YH", "G01485JJ", "G06356OH", "G35029YA", "G45504EY", "G46503DX", "G48414YA", "G57317CE", "G82830MN", "G85269DF", "G92050GC", "G92275SC", "G05724UK", "G22573RC", "G22768VO", "G43089EG", "G11629QQ", "G56784JY", "G02886BB", "G45395BF", "G52527GH", "G59536GA", "G62461SM", "G75162EY", "G14943SF", "G81315DD", "G87389XI", "G90659AW", "G25418HZ", "G33791AF", "G38663NM", "G84452RH", "G86795LJ", "G49108TO" ], "uniprot_id": "Q6P179" }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "medium", "disease": "Autoimmune phenomena", "glycan_involvement": "Glycosylation may modulate ERAP2's interaction with other immune proteins.", "mechanism": "ERAP2 genetic variation (rs1363907) is associated with increased risk of autoimmune features (e.g., ANA positivity, elevated IgG).", "protein": "ERAP2 (Endoplasmic Reticulum Aminopeptidase 2)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP2", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G45526EA", "G62765YT", "G72747WU", "G80920RR", "G90575OW", "G92135MA", "G95177YH", "G01485JJ", "G06356OH", "G35029YA", "G45504EY", "G46503DX", "G48414YA", "G57317CE", "G82830MN", "G85269DF", "G92050GC", "G92275SC", "G05724UK", "G22573RC", "G22768VO", "G43089EG", "G11629QQ", "G56784JY", "G02886BB", "G45395BF", "G52527GH", "G59536GA", "G62461SM", "G75162EY", "G14943SF", "G81315DD", "G87389XI", "G90659AW", "G25418HZ", "G33791AF", "G38663NM", "G84452RH", "G86795LJ", "G49108TO" ], "uniprot_id": "Q6P179" }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "medium", "disease": "Spondylitis", "glycan_involvement": "Glycosylation status may influence ERAP2's enzymatic activity.", "mechanism": "ERAP2 variants linked to altered antigen processing, contributing to spondylitis pathogenesis.", "protein": "ERAP2 (Endoplasmic Reticulum Aminopeptidase 2)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP2", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G45526EA", "G62765YT", "G72747WU", "G80920RR", "G90575OW", "G92135MA", "G95177YH", "G01485JJ", "G06356OH", "G35029YA", "G45504EY", "G46503DX", "G48414YA", "G57317CE", "G82830MN", "G85269DF", "G92050GC", "G92275SC", "G05724UK", "G22573RC", "G22768VO", "G43089EG", "G11629QQ", "G56784JY", "G02886BB", "G45395BF", "G52527GH", "G59536GA", "G62461SM", "G75162EY", "G14943SF", "G81315DD", "G87389XI", "G90659AW", "G25418HZ", "G33791AF", "G38663NM", "G84452RH", "G86795LJ", "G49108TO" ], "uniprot_id": "Q6P179" }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may affect ERAP2's localization and function.", "mechanism": "ERAP2 genetic variation affects peptide trimming, impacting immune response in psoriasis.", "protein": "ERAP2 (Endoplasmic Reticulum Aminopeptidase 2)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP2", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G45526EA", "G62765YT", "G72747WU", "G80920RR", "G90575OW", "G92135MA", "G95177YH", "G01485JJ", "G06356OH", "G35029YA", "G45504EY", "G46503DX", "G48414YA", "G57317CE", "G82830MN", "G85269DF", "G92050GC", "G92275SC", "G05724UK", "G22573RC", "G22768VO", "G43089EG", "G11629QQ", "G56784JY", "G02886BB", "G45395BF", "G52527GH", "G59536GA", "G62461SM", "G75162EY", "G14943SF", "G81315DD", "G87389XI", "G90659AW", "G25418HZ", "G33791AF", "G38663NM", "G84452RH", "G86795LJ", "G49108TO" ], "uniprot_id": "Q6P179" }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "high", "disease": "Amoxicillin clavulanate-induced liver injury (AC-DILI)", "glycan_involvement": "N-glycosylation critical for HLA folding and antigen presentation.", "mechanism": "HLA class I molecules present drug-peptide adducts to T cells, triggering immune-mediated liver injury.", "protein": "HLA class I molecules", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "medium", "disease": "Amoxicillin clavulanate-induced liver injury (AC-DILI)", "glycan_involvement": "Glycosylation may regulate ERAP1's activity and stability.", "mechanism": "ERAP1 trims peptides for HLA class I presentation; compensates for ERAP2 dysfunction in rs1363907 carriers.", "protein": "ERAP1 (Endoplasmic Reticulum Aminopeptidase 1)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP1", "glycan_count": 34, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO", "G02886BB", "G05049YU", "G07246CJ", "G10486CT", "G15664MX", "G24528MX", "G26330YA", "G31852PQ", "G34989PA", "G36442WJ", "G39188ZX", "G41247ZX", "G45395BF", "G49018RC", "G59324HL", "G59924QI", "G60033FS", "G62765YT", "G64527OM", "G70441OD", "G72747WU", "G73430PD", "G77669RF", "G78787DI", "G80479JV", "G80920RR", "G84225JN", "G87389XI", "G87661QW", "G88891KO", "G92406TI", "G22768VO", "G81315DD" ], "uniprot_id": "Q9NZ08" }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "high", "disease": "Autoimmune phenomena", "glycan_involvement": "IgG glycosylation modulates effector functions and immune response.", "mechanism": "Elevated IgG levels indicate autoimmune activation in AC-DILI.", "protein": "IgG (Immunoglobulin G)", "relationship_type": "biomarker", "source_pmcid": "PMC12133467" }, { "confidence": "high", "disease": "Autoimmune phenomena", "glycan_involvement": "ANA are glycoproteins; glycosylation may affect antigenicity.", "mechanism": "ANA positivity reflects autoimmune activation in AC-DILI.", "protein": "ANA (Antinuclear Antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC12133467" }, { "confidence": "medium", "disease": "Autoimmune phenomena", "glycan_involvement": "N-glycosylation essential for HLA function.", "mechanism": "Altered peptide presentation by HLA class I may trigger autoimmune responses.", "protein": "HLA class I molecules", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133467" }, { "confidence": "high", "disease": "Amoxicillin clavulanate-induced liver injury (AC-DILI)", "glycan_involvement": "Glycosylation may affect ERAP2's biomarker reliability.", "mechanism": "Presence of ERAP2 rs1363907 mutation serves as a genetic biomarker for AC-DILI risk.", "protein": "ERAP2 (Endoplasmic Reticulum Aminopeptidase 2)", "protein_enriched": { "function": "Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor pepti", "gene_name": "ERAP2", "glycan_count": 46, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G23719VF", "G31852PQ", "G36379GD", "G39188ZX", "G41247ZX", "G45526EA", "G62765YT", "G72747WU", "G80920RR", "G90575OW", "G92135MA", "G95177YH", "G01485JJ", "G06356OH", "G35029YA", "G45504EY", "G46503DX", "G48414YA", "G57317CE", "G82830MN", "G85269DF", "G92050GC", "G92275SC", "G05724UK", "G22573RC", "G22768VO", "G43089EG", "G11629QQ", "G56784JY", "G02886BB", "G45395BF", "G52527GH", "G59536GA", "G62461SM", "G75162EY", "G14943SF", "G81315DD", "G87389XI", "G90659AW", "G25418HZ", "G33791AF", "G38663NM", "G84452RH", "G86795LJ", "G49108TO" ], "uniprot_id": "Q6P179" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133467" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Platelets, neutrophils, and lymphocytes are glycoprotein-rich cells; glycosylation affects their function and SII value.", "mechanism": "SII negatively correlates with hepatic fibrosis markers (FIB-4, NFS); lower SII reflects immune cell apoptosis and fibrosis progression after heavy metal exposure.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "biomarker", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "AQP9 is glycosylated, impacting its membrane localization and arsenic transport.", "mechanism": "Reduced AQP9 expression decreases intracellular arsenic accumulation, affecting arsenic trioxide sensitivity in leukemia treatment.", "protein": "Aquaporin-9 (AQP9)", "protein_enriched": { "function": "Neurotrophic factor that regulates central nervous development and function", "gene_name": "FGF20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NP95" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133468" }, { "confidence": "high", "disease": "Hepatic steatosis (NAFLD)", "glycan_involvement": "Indirect; immune cell glycosylation may affect SII but not steatosis.", "mechanism": "No significant association found between SII and hepatic steatosis indices (FLI, LFS, FSI).", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "biomarker", "source_pmcid": "PMC12133468" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Immune cell glycosylation modulates cell survival and inflammation.", "mechanism": "Heavy metals (As, Co) reduce SII, which mediates and promotes hepatic fibrosis progression.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "causal", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation of immune cells may influence anti-fibrotic signaling.", "mechanism": "Cesium (Cs) exposure reduces SII, which mediates anti-fibrotic protection.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "protective", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "GATA-2 function may be modulated by glycosylation.", "mechanism": "Arsenic reduces GATA-2 DNA-binding activity, suppressing hematopoiesis and immune cell differentiation.", "protein": "GATA-2", "protein_enriched": { "function": "Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'", "gene_name": "GATA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23769" }, "relationship_type": "causal", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "ALT is glycosylated, affecting its stability and serum levels.", "mechanism": "ALT is a traditional marker for hepatic injury; its accuracy is limited compared to composite indices.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "AST glycosylation influences its serum activity.", "mechanism": "AST is used in NAFLD risk indices (FSI); reflects liver cell damage.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "Immune cell glycosylation affects SII and drug response.", "mechanism": "Arsenic trioxide modulates immune cell populations reflected in SII, relevant for leukemia therapy.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133468" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation of immune cells modulates SII.", "mechanism": "SII reflects immune cell status and inflammation, relevant in arsenic-based immunomodulation.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "biomarker", "source_pmcid": "PMC12133468" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HSI includes glycoprotein-based serum markers (e.g., ALT, AST) reflecting liver glycoprotein metabolism.", "mechanism": "HSI is used as a non-invasive biomarker to assess hepatic steatosis severity and progression.", "protein": "Hepatic Steatosis Index (HSI)", "relationship_type": "biomarker", "source_pmcid": "PMC12133482" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect Sirtuin 4 stability and function in mitochondrial stress response.", "mechanism": "MedDiet may modulate Sirtuin 4, which regulates oxidative stress and inflammation in liver cells.", "protein": "Sirtuin 4", "protein_enriched": { "function": "Acts as a NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879). Catalyzes more efficiently remov", "gene_name": "SIRT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6E7" }, "relationship_type": "protective", "source_pmcid": "PMC12133482" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL particles contain apolipoprotein B, a glycoprotein whose glycosylation affects lipid transport.", "mechanism": "Elevated LDL-C is a risk factor for cardiovascular disease; MedDiet lowers LDL-C, reducing risk.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC12133482" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "HDL contains apolipoprotein A-I, a glycoprotein; glycosylation modulates its anti-inflammatory properties.", "mechanism": "Higher HDL-C is protective against cardiovascular disease; MedDiet increases HDL-C.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12133482" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Serum glycoprotein markers in HSI are altered in T2D due to changes in glycosylation.", "mechanism": "HSI is elevated in T2D, reflecting increased hepatic fat and insulin resistance.", "protein": "Hepatic Steatosis Index (HSI)", "relationship_type": "biomarker", "source_pmcid": "PMC12133482" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Altered glycoprotein metabolism in liver cancer affects HSI components.", "mechanism": "High HSI is a risk factor for progression to hepatocellular carcinoma.", "protein": "Hepatic Steatosis Index (HSI)", "relationship_type": "biomarker", "source_pmcid": "PMC12133482" }, { "confidence": "low", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation may regulate Sirtuin 4 activity in cardiac tissue.", "mechanism": "Sirtuin 4 modulates mitochondrial function and reduces oxidative stress, lowering cardiovascular risk.", "protein": "Sirtuin 4", "protein_enriched": { "function": "Acts as a NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879). Catalyzes more efficiently remov", "gene_name": "SIRT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6E7" }, "relationship_type": "protective", "source_pmcid": "PMC12133482" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Apolipoprotein B glycosylation affects LDL clearance and hepatic uptake.", "mechanism": "Elevated LDL-C contributes to hepatic fat accumulation and MASLD progression.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "causal", "source_pmcid": "PMC12133482" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Apolipoprotein A-I glycosylation enhances anti-steatotic effects.", "mechanism": "Higher HDL-C is associated with reduced hepatic steatosis.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12133482" }, { "confidence": "low", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Potential glycosylation-dependent modulation of Sirtuin 4 in cancer cells.", "mechanism": "Sirtuin 4 may suppress carcinogenesis via mitochondrial regulation.", "protein": "Sirtuin 4", "protein_enriched": { "function": "Acts as a NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879). Catalyzes more efficiently remov", "gene_name": "SIRT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6E7" }, "relationship_type": "protective", "source_pmcid": "PMC12133482" }, { "confidence": "high", "disease": "Hepatitis D (HDV infection)", "glycan_involvement": "HBsAg is a glycoprotein; its glycosylation is essential for viral particle formation and infectivity.", "mechanism": "HBsAg is required for HDV virion assembly and hepatocyte entry.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "Chronic hepatitis D", "glycan_involvement": "Glycosylation of HBsAg affects immune recognition and viral persistence.", "mechanism": "Persistent HBsAg enables chronic HDV infection and disease progression.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "Hepatitis D (HDV infection)", "glycan_involvement": "No direct glycosylation reported for HDAg.", "mechanism": "HDAg is detected in serum/liver as a marker of active HDV replication.", "protein": "Hepatitis D antigen (HDAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "Hepatitis D (HDV infection)", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects antibody stability and function.", "mechanism": "Serum anti-HDV IgG/IgM indicates exposure or infection with HDV.", "protein": "Anti-HDV antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12133488" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "Glycosylation of HBsAg may modulate oncogenic potential.", "mechanism": "HBsAg-mediated HDV infection increases risk of liver cancer.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation of HBsAg is important for viral assembly and chronicity.", "mechanism": "HBsAg enables HDV superinfection, accelerating progression to cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "Chronic hepatitis D", "glycan_involvement": "Antibody glycosylation influences immune response and diagnostic accuracy.", "mechanism": "Persistent anti-HDV IgG/IgM indicates chronic HDV infection.", "protein": "Anti-HDV antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12133488" }, { "confidence": "medium", "disease": "Chronic hepatitis D", "glycan_involvement": "No direct glycosylation reported for HDAg.", "mechanism": "Transient detection of HDAg in serum/liver is associated with active HDV replication.", "protein": "Hepatitis D antigen (HDAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12133488" }, { "confidence": "medium", "disease": "Hepatitis D (HDV infection)", "glycan_involvement": "Glycosylation sites on HBsAg may be targeted for antiviral strategies.", "mechanism": "Targeting HBsAg can prevent HDV virion formation and infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133488" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "Glycosylation of antibodies affects diagnostic sensitivity.", "mechanism": "Anti-HDV antibodies are used to screen for HDV infection, which increases liver cancer risk.", "protein": "Anti-HDV antibody (IgG/IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12133488" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding affinity.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2, facilitating infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "high", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation affects ACE2 stability and interaction with spike protein.", "mechanism": "ACE2 is highly expressed in pancreatic islets; SARS-CoV-2 binding disrupts islet function, contributing to new-onset DM.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "high", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Heavily glycosylated S protein shields epitopes and mediates cell entry.", "mechanism": "Spike protein binds ACE2 on beta cells, leading to cell dysfunction and impaired insulin secretion.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "high", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation required for insulin maturation and secretion.", "mechanism": "Reduced insulin production due to beta cell damage by SARS-CoV-2 leads to hyperglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects DPP-4 enzymatic activity and stability.", "mechanism": "DPP-4 inhibitors may modulate inflammation and improve outcomes in COVID-19 patients with DM.", "protein": "DPP-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation essential for adiponectin multimerization and function.", "mechanism": "Reduced adiponectin in COVID-19 patients contributes to insulin resistance and worsened glycemic control.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "Thromboembolism", "glycan_involvement": "Glycosylation modulates fibrin clot structure and function.", "mechanism": "Fibrin binds SARS-CoV-2 spike protein, forming pro-inflammatory clots and increasing thromboembolic risk.", "protein": "Fibrin", "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "GLP-1R agonists upregulate ACE2, potentially increasing SARS-CoV-2 susceptibility but improving glycemic control.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor interaction.", "mechanism": "COVID-19-induced cytokine storm (including TNF-\u03b1) increases insulin resistance and beta cell dysfunction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation required for IL-6 stability and activity.", "mechanism": "Elevated IL-6 in COVID-19 promotes systemic inflammation, insulin resistance, and worsens DM outcomes.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12133490" }, { "confidence": "high", "disease": "Cardiometabolic disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function as an inflammatory marker.", "mechanism": "CRP levels are elevated in cardiometabolic disease and reduced by OEA supplementation, reflecting decreased inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12133512" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "TNF-\u03b1 is glycosylated, which modulates its secretion and activity.", "mechanism": "TNF-\u03b1 is elevated in obesity; OEA supplementation reduces TNF-\u03b1, indicating anti-inflammatory effects.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "IL-6 glycosylation affects receptor binding and stability.", "mechanism": "IL-6 is elevated in obesity; OEA supplementation showed no significant effect on IL-6 levels.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "GLP-1 is glycosylated, influencing its half-life and activity.", "mechanism": "OEA stimulates GLP-1 secretion, improving insulin secretion and glycemic control.", "protein": "GLP-1 (Glucagon-like peptide-1)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Adiponectin glycosylation is critical for multimerization and bioactivity.", "mechanism": "OEA increases adiponectin, enhancing insulin sensitivity and glucose uptake.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Resistin is glycosylated, affecting its secretion and inflammatory activity.", "mechanism": "OEA reduces resistin, which is associated with improved insulin sensitivity.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "CD36 is heavily glycosylated, which regulates its membrane localization and fatty acid transport.", "mechanism": "CD36 mediates oleic acid uptake, influencing OEA synthesis and lipid metabolism.", "protein": "FAT/CD36", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12133512" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Insulin glycosylation is minimal but glycan interactions affect receptor binding.", "mechanism": "OEA supplementation reduces fasting insulin levels, improving glycemic control.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation, not classical glycosylation.", "mechanism": "HbA1c reflects long-term glycemic control; OEA supplementation showed no significant effect.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12133512" }, { "confidence": "medium", "disease": "Cardiometabolic disease", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB) whose glycosylation affects lipid transport.", "mechanism": "LDL-C is a risk factor for cardiometabolic disease; OEA supplementation did not significantly alter LDL-C levels.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12133512" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation stabilizes soluble receptor and affects clearance.", "mechanism": "Elevated sTNFR1 correlates with inflammation and severity of nephropathy.", "protein": "sTNFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "high", "disease": "Cardiovascular events", "glycan_involvement": "Glycosylation modulates receptor solubility and bioactivity.", "mechanism": "High sTNFR2 levels predict increased risk of cardiovascular events in diabetes.", "protein": "sTNFR2", "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "high", "disease": "Diabetic retinopathy", "glycan_involvement": "N-glycosylation required for VEGF secretion and receptor binding.", "mechanism": "VEGF promotes angiogenesis and vascular permeability in retinopathy.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation affects PTX3 stability and immune interactions.", "mechanism": "PTX3 promotes M2 macrophage differentiation, reducing fibrosis.", "protein": "PTX3", "relationship_type": "protective", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "N-glycosylation modulates CD80 surface expression and T cell activation.", "mechanism": "CD80+ DCs accumulate in kidney, correlating with fibrosis and dysfunction.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "causal", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation regulates CD86 stability and immune synapse formation.", "mechanism": "CD86+ DCs contribute to immune activation and renal injury.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "causal", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Diabetic cerebrovascular disease", "glycan_involvement": "N-glycosylation essential for ICAM-1 function and leukocyte adhesion.", "mechanism": "Elevated soluble ICAM-1 reflects endothelial activation and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates VCAM-1 binding to immune cells.", "mechanism": "High VCAM-1 levels indicate vascular inflammation and plaque formation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Diabetic peripheral arterial disease", "glycan_involvement": "Glycosylation affects CD14 receptor function and LPS binding.", "mechanism": "CD14+ monocytes infiltrate arterial wall, promoting inflammation and plaque.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "medium", "disease": "Diabetic peripheral arterial disease", "glycan_involvement": "Glycosylation modulates CD64 affinity for IgG and immune activation.", "mechanism": "High CD64 expression on monocytes linked to atherosclerosis progression.", "protein": "CD64", "relationship_type": "biomarker", "source_pmcid": "PMC12133520" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "RBP is N-glycosylated; glycosylation status may affect stability and clearance.", "mechanism": "RBP levels decrease as liver synthetic function declines; lower RBP reflects greater cirrhosis severity.", "protein": "Retinol Binding Protein (RBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12133530" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Impaired glycosylation may further reduce RBP secretion.", "mechanism": "Reduced hepatic synthesis of RBP due to hepatocyte dysfunction in cirrhosis.", "protein": "Retinol Binding Protein (RBP)", "relationship_type": "causal", "source_pmcid": "PMC12133530" }, { "confidence": "high", "disease": "Invasive aspergillosis (IA)", "glycan_involvement": "Glycosylation affects RBP plasma stability, impacting its biomarker utility.", "mechanism": "RBP used to optimize voriconazole dosing in IA patients with cirrhosis, improving therapeutic outcomes.", "protein": "Retinol Binding Protein (RBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12133530" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation status may influence RBP measurement accuracy.", "mechanism": "RBP-guided voriconazole dosing enables individualized therapy in cirrhosis.", "protein": "Retinol Binding Protein (RBP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133530" }, { "confidence": "high", "disease": "Anti-SRP IMNM", "glycan_involvement": "SRP54 is targeted by glycosylated IgG autoantibodies.", "mechanism": "Autoantibodies against SRP54 induce muscle fiber necrosis and atrophy.", "protein": "SRP54", "relationship_type": "causal", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-HMGCR IMNM", "glycan_involvement": "HMGCR is targeted by glycosylated IgG1 autoantibodies.", "mechanism": "Autoantibodies against HMGCR induce muscle fiber necrosis, often associated with statin exposure.", "protein": "HMGCR", "relationship_type": "causal", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-SRP IMNM", "glycan_involvement": "IgG1 glycosylation affects Fc receptor binding and effector function.", "mechanism": "IgG1 autoantibodies mediate complement activation and cytotoxicity against muscle fibers.", "protein": "IgG1", "relationship_type": "causal", "source_pmcid": "PMC12133534" }, { "confidence": "medium", "disease": "Anti-SRP IMNM", "glycan_involvement": "IgG4 glycosylation modulates immunomodulatory properties.", "mechanism": "IgG4 autoantibodies present in some patients, with lower complement activation.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "causal", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-SRP IMNM", "glycan_involvement": "Fc glycosylation is essential for FcRn binding and therapeutic efficacy.", "mechanism": "Efgartigimod binds FcRn, accelerates IgG degradation, reducing pathogenic autoantibodies.", "protein": "Fc fragment of IgG1 (efgartigimod)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-SRP IMNM", "glycan_involvement": "FcRn glycosylation affects IgG binding and trafficking.", "mechanism": "FcRn regulates IgG recycling; inhibition leads to increased IgG degradation.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-SRP IMNM", "glycan_involvement": "Antibody glycosylation influences pathogenicity and detection.", "mechanism": "Presence of anti-SRP antibody correlates with disease activity and severity.", "protein": "Anti-SRP antibody", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "Anti-HMGCR IMNM", "glycan_involvement": "Antibody glycosylation influences pathogenicity and detection.", "mechanism": "Presence of anti-HMGCR antibody correlates with statin-induced myopathy and IMNM.", "protein": "Anti-HMGCR antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12133534" }, { "confidence": "medium", "disease": "IMNM", "glycan_involvement": "MHC-I is a glycoprotein; glycosylation affects antigen presentation.", "mechanism": "Upregulated MHC-I expression in muscle biopsy is a pathological feature of IMNM.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12133534" }, { "confidence": "medium", "disease": "IMNM", "glycan_involvement": "MAC components are glycoproteins; glycosylation affects assembly and function.", "mechanism": "MAC deposition in muscle fibers indicates complement-mediated damage.", "protein": "Membrane Attack Complex (MAC)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12133534" }, { "confidence": "high", "disease": "CADASIL", "glycan_involvement": "Mutations interfere with glycosylation of EGFr domains, affecting protein folding and aggregation.", "mechanism": "Missense mutations in NOTCH3 disrupt cysteine residues in EGFr domains, leading to protein misfolding, aggregation, and vascular smooth muscle cell degeneration.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12133546" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Altered glycosylation contributes to abnormal NOTCH3 aggregation.", "mechanism": "NOTCH3 mutations (especially in EGFr1-6) increase aggregation and vascular dysfunction, leading to early-onset stroke.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12133546" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "Glycosylation defects promote aggregation and neurovascular damage.", "mechanism": "NOTCH3 aggregation and signaling dysfunction cause progressive cognitive decline.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "Migraine", "glycan_involvement": "Indirect; glycosylation defects contribute to vascular pathology.", "mechanism": "NOTCH3 mutations are associated with migraine as an early clinical manifestation of CADASIL.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "TIMP3 glycosylation may affect its interaction with NOTCH3 aggregates.", "mechanism": "NOTCH3 ECD recruits TIMP3 to form aggregates; reduction of TIMP3 improves CADASIL phenotype in mouse models.", "protein": "TIMP3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "VTN glycosylation may modulate aggregate formation.", "mechanism": "VTN is recruited by NOTCH3 ECD aggregates; reduction of VTN ameliorates disease severity.", "protein": "Vitronectin (VTN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "HTRA1 glycosylation may influence protein-protein interactions.", "mechanism": "NOTCH3 N-terminal EGFr domains interact with HTRA1, enhancing protein multimerization and aggregate load.", "protein": "HTRA1", "protein_enriched": { "function": "Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3", "gene_name": "HTRA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92743" }, "relationship_type": "modifier", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "LTBP1 glycosylation may affect aggregate stability.", "mechanism": "LTBP1 interacts with NOTCH3 aggregates, contributing to vascular pathology.", "protein": "LTBP1", "protein_enriched": { "function": "May play an integral structural role in elastic-fiber architectural organization and/or assembly", "gene_name": "LTBP2", "glycan_count": 41, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G71142DF", "G57321FI", "G29068FM", "G43669FQ", "G45395BF", "G43417UB", "G88713AC", "G29063QY", "G57317CE", "G53434XO", "G10488MI", "G20706XG", "G51640FO", "G77669RF", "G84225JN", "G84452RH", "G00406II", "G03382KH", "G04657PL", "G05049YU", "G10256JP", "G17208MA", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G41071NU", "G42124LM", "G46687AB", "G46691LC", "G46902YN", "G60177UT", "G66621EA", "G70101JE", "G76295SF", "G80223IX", "G90659AW", "G91636VS", "G14972EH", "G43223CG", "G49108TO" ], "uniprot_id": "Q14767" }, "relationship_type": "modifier", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "APOE glycosylation may influence its role in lipid transport and vascular pathology.", "mechanism": "APOE \u03b52 allele is associated with higher WMH volume and more severe cognitive impairment in CADASIL.", "protein": "APOE", "relationship_type": "modifier", "source_pmcid": "PMC12133546" }, { "confidence": "medium", "disease": "CADASIL", "glycan_involvement": "GLUT4 glycosylation is essential for membrane localization and function.", "mechanism": "Downregulation of GLUT4 in VSMCs impairs glucose uptake, contributing to blood flow restriction and disease severity.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "modifier", "source_pmcid": "PMC12133546" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "LMWH glycan chain interacts with ATIII glycosylation sites.", "mechanism": "LMWH binds ATIII, potentiates inhibition of Factor Xa and IIa, reducing thrombosis.", "protein": "Antithrombin III (ATIII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "HSPG glycosylation mediates viral attachment; LMWH competes for binding.", "mechanism": "LMWH blocks SARS-CoV-2 spike protein binding to HSPGs, preventing viral entry.", "protein": "Heparan sulfate proteoglycans (HSPGs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "IFN-\u03b3 glycosylation may affect LMWH binding affinity.", "mechanism": "LMWH binds IFN-\u03b3, inhibits receptor interaction, dampening inflammation.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "IL-6 glycosylation modulates complex formation and LMWH interaction.", "mechanism": "LMWH binds IL-6 or IL-6/IL-6R\u03b1 complex, inhibits signaling, reduces inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "\u03b22GP\u2160 glycosylation influences antibody binding and LMWH effect.", "mechanism": "Antiphospholipid antibodies bind \u03b22GP\u2160, promoting thrombosis; LMWH reduces risk.", "protein": "\u03b22-glycoprotein I (\u03b22GP\u2160)", "relationship_type": "causal", "source_pmcid": "PMC12133558" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "VEGF glycosylation affects receptor interaction and LMWH inhibition.", "mechanism": "LMWH inhibits VEGF binding to receptor, suppresses angiogenesis and tumor growth.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "HSPG glycosylation critical for glycocalyx integrity and LMWH effect.", "mechanism": "LMWH stabilizes endothelial glycocalyx via HSPG binding, reduces vascular damage.", "protein": "Heparan sulfate proteoglycans (HSPGs)", "relationship_type": "protective", "source_pmcid": "PMC12133558" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation may influence protein function and LMWH interaction.", "mechanism": "LMWH may regulate heparin-binding protein levels, affecting iron metabolism.", "protein": "Heparin-binding protein", "protein_enriched": { "function": "Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. Signals through CCR2B and CCR3 receptors. Plays a role in the accumulation of leukocytes at bot", "gene_name": "CCL13", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99616" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133558" }, { "confidence": "medium", "disease": "Ulcerative colitis (UC)", "glycan_involvement": "Integrin glycosylation modulates LMWH targeting and efficacy.", "mechanism": "LMWH binds integrin \u03b1M, targets inflammatory sites, regulates redox homeostasis.", "protein": "Integrin \u03b1M", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein glycosylation affects LMWH binding and viral entry.", "mechanism": "LMWH binds spike protein RBD, induces conformational change, blocks ACE2 interaction.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133558" }, { "confidence": "high", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "Albumin is N-glycosylated, affecting its stability and function.", "mechanism": "Low serum albumin is independently associated with increased in-hospital mortality; reflects antioxidant, anti-inflammatory, and antithrombotic capacity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation modulates albumin's antioxidant properties.", "mechanism": "Low albumin at admission correlates with all-cause mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Coronary Syndrome (ACS)", "glycan_involvement": "Glycosylation status may affect albumin's vascular protective effects.", "mechanism": "Low serum albumin increases risk for all-cause mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133610" }, { "confidence": "high", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "MMP-9 is glycosylated, which affects secretion and activity.", "mechanism": "Neutrophil-secreted MMP-9 degrades aortic extracellular matrix, promoting dissection and rupture.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and stability.", "mechanism": "IL-6 released by neutrophils drives inflammation and vascular injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "TNF-\u03b1 glycosylation affects bioactivity and receptor interaction.", "mechanism": "TNF-\u03b1 promotes inflammatory cascade and endothelial damage.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "Antithrombin III glycosylation is essential for anticoagulant function.", "mechanism": "Albumin enhances antithrombin III activity, reducing thrombosis risk.", "protein": "Antithrombin III", "relationship_type": "protective", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "NETs contain glycoproteins (e.g., histones, granule proteins) that mediate immune and thrombotic effects.", "mechanism": "NETs exacerbate endothelial injury and promote thrombosis.", "protein": "Neutrophil extracellular traps (NETs)", "relationship_type": "causal", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Type A Aortic Dissection (AAAD)", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIIb/IIIa) are critical for aggregation; glycosylation modulates function.", "mechanism": "Reduced albumin leads to increased platelet activation and aggregation, raising thrombosis risk.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133610" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may affect albumin's renal protective effects.", "mechanism": "Low albumin and high NPAR are associated with increased AKI incidence post-AAAD surgery.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133610" }, { "confidence": "high", "disease": "DWMH/PVWMH/TWMH", "glycan_involvement": "Glycosylation may affect DHA transport and membrane incorporation.", "mechanism": "Inverse association with WMH volume; enhances BBB integrity, suppresses neuroinflammation.", "protein": "Docosahexaenoic acid (DHA)", "relationship_type": "protective biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "high", "disease": "DWMH/TWMH", "glycan_involvement": "Glycosylation may modulate bioavailability.", "mechanism": "Inverse association with lesion volume; anti-inflammatory and antioxidant effects.", "protein": "Stearidonic acid (SDA)", "relationship_type": "protective biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "DWMH", "glycan_involvement": "Glycosylation may influence metabolic fate.", "mechanism": "Marginal negative association; balance with \u03c9-3 PUFA is critical for inflammation regulation.", "protein": "Linoleic acid (LA)", "relationship_type": "protective/complex biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "PVWMH", "glycan_involvement": "Glycosylation may affect mitochondrial transport.", "mechanism": "Reflect impaired mitochondrial \u03b2-oxidation; may contribute to non-ischemic fluid accumulation.", "protein": "Carnitine derivatives (e.g., palmitoylcarnitine)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "DWMH", "glycan_involvement": "Glycosylation may regulate receptor binding.", "mechanism": "Induces microvascular endothelial dysfunction via EP receptor activation.", "protein": "Prostaglandin E2 (PGE2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "DWMH", "glycan_involvement": "Not directly glycosylated; may affect glycoprotein COX-2.", "mechanism": "COX-2 inhibitor; ameliorates microcirculatory impairment.", "protein": "Etodolac", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133732" }, { "confidence": "high", "disease": "CSVD/WMH", "glycan_involvement": "N-glycosylation may regulate sEH activity and stability.", "mechanism": "Elevated sEH activity increases pro-oxidative metabolites, exacerbating vascular damage.", "protein": "Soluble epoxide hydrolase (sEH)", "protein_enriched": { "function": "Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia fo", "gene_name": "ABI2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NYB9" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "Neuroinflammation/WMH", "glycan_involvement": "Glycosylation may affect receptor interactions.", "mechanism": "DHA metabolite; activates PPAR pathway, reduces oxidative stress and neuronal damage.", "protein": "Neuroprotectin D1 (NPD1)", "relationship_type": "protective biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "high", "disease": "BBB disruption/WMH", "glycan_involvement": "N-glycosylation critical for tight junction function.", "mechanism": "Upregulated by DHA; reinforces BBB integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12133732" }, { "confidence": "medium", "disease": "WMH", "glycan_involvement": "Glycosylation may affect metabolic conversion.", "mechanism": "Downregulated in WMH; involved in anti-inflammatory pathways.", "protein": "\u03b3-Linolenic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12133732" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects HER2 stability and antibody binding.", "mechanism": "HER2 is overexpressed in certain breast cancers and targeted by ADCs for selective cytotoxic delivery.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Solid tumors (general)", "glycan_involvement": "Glycosylation modulates TROP2 cell surface expression.", "mechanism": "TROP2 is highly expressed in various solid tumors and targeted by ADCs.", "protein": "TROP2", "protein_enriched": { "function": "May be involved in transcriptional regulation", "gene_name": "ZNF101", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZC7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Hematological malignancies", "glycan_involvement": "Glycosylation influences CD22 antibody recognition.", "mechanism": "CD22 is a B-cell marker targeted by ADCs in blood cancers.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Hematological malignancies", "glycan_involvement": "Glycosylation affects CD33 antigenicity.", "mechanism": "CD33 is expressed on myeloid cells and targeted by ADCs in leukemia.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation modulates EGFR ligand binding and antibody accessibility.", "mechanism": "EGFR is overexpressed/mutated in NSCLC and targeted by ADCs and Probody-drug conjugates.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Lymphoma", "glycan_involvement": "Afucosylation of antibody Fc increases ADCC.", "mechanism": "CCR4 is targeted by afucosylated antibodies (mogamulizumab) for enhanced ADCC in lymphoma.", "protein": "CCR4", "protein_enriched": { "function": "High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calc", "gene_name": "CCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "medium", "disease": "Solid tumors (general)", "glycan_involvement": "Glycosylation may affect antibody binding specificity.", "mechanism": "CD166 is targeted by Probody-drug conjugates to minimize off-tumor toxicity.", "protein": "CD166", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "medium", "disease": "Solid tumors (general)", "glycan_involvement": "Glycosylation may influence immune modulation.", "mechanism": "B7-H3 is targeted by bispecific ADCs for enhanced tumor selectivity.", "protein": "B7-H3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "medium", "disease": "Hematological malignancies", "glycan_involvement": "Glycosylation affects antigen presentation.", "mechanism": "CD79 is targeted by ADCs in B-cell cancers.", "protein": "CD79", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "medium", "disease": "Cetuximab-resistant tumors", "glycan_involvement": "Glycosylation may affect antibody binding and resistance.", "mechanism": "HER2-targeted Probody-drug conjugates overcome resistance in cetuximab-resistant models.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133739" }, { "confidence": "high", "disease": "Post-menopausal obesity", "glycan_involvement": "Glycosylation modulates ER\u03b1 stability and function.", "mechanism": "Phytoestrogens upregulate ER\u03b1 expression, restoring estrogenic signaling and improving metabolic balance.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "high", "disease": "Post-menopausal obesity", "glycan_involvement": "Glycosylation affects receptor localization and activity.", "mechanism": "Phytoestrogens enhance ER\u03b2 expression, contributing to anti-obesity effects.", "protein": "Estrogen Receptor beta (ER\u03b2)", "protein_enriched": { "function": "Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-depen", "gene_name": "ESR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92731" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Adiponectin function depends on glycosylation for multimerization and activity.", "mechanism": "Medicinal plants downregulate Adipoq in hypertrophic adipocytes, reducing insulin resistance.", "protein": "Adiponectin (Adipoq)", "protein_enriched": { "function": "", "gene_name": "tat", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3S5G7" }, "relationship_type": "protective", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Post-menopausal obesity", "glycan_involvement": "Glycosylation may affect Plin1 stability and lipid droplet association.", "mechanism": "Plant extracts downregulate Plin1, promoting lipolysis and reducing fat accumulation.", "protein": "Perilipin 1 (Plin1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Leptin glycosylation is essential for secretion and bioactivity.", "mechanism": "Leptin levels are modulated by phytoestrogen treatment, reflecting improved adipose tissue function.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133798" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation is critical for LDLR folding and function.", "mechanism": "Phytoestrogens upregulate LDLR, enhancing LDL clearance and improving lipid profiles.", "protein": "Low-Density Lipoprotein Receptor (LDLR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation regulates GLUT4 trafficking and activity.", "mechanism": "Medicinal plants increase GLUT4 expression, improving glucose uptake in adipose tissue.", "protein": "Glucose Transporter 4 (GLUT4/SLC2A4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Adipose tissue inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "Estrogen deficiency increases TNF-\u03b1, promoting inflammation; phytoestrogens reduce TNF-\u03b1 expression.", "protein": "Tumor Necrosis Factor alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Adipose tissue inflammation", "glycan_involvement": "Glycosylation modulates IL-6 stability and signaling.", "mechanism": "IL-6 is elevated in post-menopausal obesity; medicinal plants reduce IL-6, lowering inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12133798" }, { "confidence": "medium", "disease": "Post-menopausal obesity", "glycan_involvement": "Glycosylation may influence UCP-1 mitochondrial localization.", "mechanism": "Phytoestrogens upregulate UCP-1, promoting WAT browning and increased energy expenditure.", "protein": "UCP-1 (Uncoupling Protein 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133798" }, { "confidence": "high", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "TMAO production depends on gut microbial metabolism of choline/carnitine, which are often glycosylated; TMAO itself is not a glycoprotein.", "mechanism": "TMAO levels predict major adverse cardiac events and are elevated in STEMI; TMAO disrupts cholesterol transport and promotes foam cell formation.", "protein": "TMAO (Trimethylamine N-oxide)", "relationship_type": "biomarker", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "FMO3 is N-glycosylated, which may affect its stability and activity.", "mechanism": "FMO3 catalyzes oxidation of TMA to TMAO, influencing TMAO levels and thus cardiovascular risk.", "protein": "FMO3 (Flavin-containing monooxygenase 3)", "protein_enriched": { "function": "Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. Catalyzes two of the four reactions of the long", "gene_name": "EHHADH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q08426" }, "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "UDP-GlcNAc is a key substrate for N- and O-glycosylation of proteins, potentially affecting glycoprotein function in the heart and vasculature.", "mechanism": "Increased UDP-N-acetylglucosamine biosynthesis pathway (UDPNAGSYN-PWY) is associated with higher TMAO and adverse cardiac function.", "protein": "UDP-N-acetylglucosamine biosynthesis enzymes", "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "ABCA1 is N-glycosylated; glycosylation affects its trafficking and function.", "mechanism": "Butyrate-producing bacteria (increased by polyphenols) enhance ABCA1 expression, improving cholesterol efflux and reducing atherosclerosis risk.", "protein": "ABCA1 (ATP-binding cassette transporter A1)", "relationship_type": "protective", "source_pmcid": "PMC12133805" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Indirect; TMAO production is linked to metabolism of glycan-containing dietary precursors.", "mechanism": "TMAO promotes atherosclerosis by impairing cholesterol clearance and increasing foam cell formation.", "protein": "TMAO (Trimethylamine N-oxide)", "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "high", "disease": "Major adverse cardiac events (MACE)", "glycan_involvement": "Indirect, as above.", "mechanism": "Elevated TMAO predicts increased risk of MACE in STEMI patients.", "protein": "TMAO (Trimethylamine N-oxide)", "relationship_type": "biomarker", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Direct; UDP-GlcNAc is central to glycosylation of host and microbial proteins.", "mechanism": "Increased UDP-GlcNAc pathway activity may facilitate bacterial cell wall synthesis and promote gut dysbiosis, contributing to atherosclerosis.", "protein": "UDP-N-acetylglucosamine biosynthesis enzymes", "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation may regulate FMO3 activity.", "mechanism": "FMO3 activity increases TMAO, which promotes atherosclerosis.", "protein": "FMO3 (Flavin-containing monooxygenase 3)", "protein_enriched": { "function": "Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. Catalyzes two of the four reactions of the long", "gene_name": "EHHADH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q08426" }, "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "N-glycosylation required for ABCA1 function.", "mechanism": "Enhanced ABCA1 function (via butyrate) improves cholesterol efflux, reducing coronary artery disease risk.", "protein": "ABCA1 (ATP-binding cassette transporter A1)", "relationship_type": "protective", "source_pmcid": "PMC12133805" }, { "confidence": "low", "disease": "Coronary artery disease", "glycan_involvement": "Central to N- and O-glycosylation.", "mechanism": "Altered glycan biosynthesis may affect gut microbiota and host glycoprotein function, influencing disease risk.", "protein": "UDP-N-acetylglucosamine biosynthesis enzymes", "relationship_type": "causal", "source_pmcid": "PMC12133805" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation modulates ligand binding and immune regulation.", "mechanism": "PD-1 inhibitors block immune checkpoint, enhancing anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "PD-L1 glycosylation affects stability and immune recognition.", "mechanism": "PD-L1 inhibitors block immune evasion by tumor cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "VEGFA is a glycoprotein; glycosylation affects its secretion and receptor binding.", "mechanism": "Bevacizumab inhibits VEGFA-mediated angiogenesis, reducing tumor vascularization.", "protein": "Bevacizumab (targets VEGFA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "EGFR-mutant NSCLC", "glycan_involvement": "EGFR is N-glycosylated, which modulates receptor function and drug response.", "mechanism": "EGFR mutations drive tumor growth; status guides therapy selection.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "ALK-mutant NSCLC", "glycan_involvement": "ALK is a glycoprotein; glycosylation may affect receptor stability.", "mechanism": "ALK rearrangements drive oncogenesis; status guides targeted therapy.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation of PD-L1 influences detection and immune evasion.", "mechanism": "PD-L1 expression predicts response to immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "EGFR-mutant NSCLC", "glycan_involvement": "Glycosylation may affect PD-1 function and therapy response.", "mechanism": "PD-1 inhibitors used after resistance to EGFR-targeted therapy.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "VEGFA glycosylation modulates angiogenic activity.", "mechanism": "Bevacizumab added to chemotherapy improves PFS in advanced cases.", "protein": "Bevacizumab (targets VEGFA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "medium", "disease": "EGFR-mutant NSCLC", "glycan_involvement": "Glycosylation affects PD-L1 stability and immune interactions.", "mechanism": "PD-L1 expression may influence immunotherapy efficacy in EGFR-mutant tumors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133818" }, { "confidence": "low", "disease": "ALK-mutant NSCLC", "glycan_involvement": "Glycosylation may modulate PD-1 function.", "mechanism": "PD-1 inhibitors considered after ALK-targeted therapy resistance.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133818" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates host cell binding.", "mechanism": "Spike glycoprotein mediates viral entry into lung epithelial cells, initiating infection.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12133828" }, { "confidence": "medium", "disease": "Acute Cellular Rejection (ACR)", "glycan_involvement": "Glycosylation may modulate immune recognition but no significant effect observed.", "mechanism": "Spike-mediated infection hypothesized to trigger immune activation and rejection; not supported by data.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (investigated, not significant)", "source_pmcid": "PMC12133828" }, { "confidence": "high", "disease": "All-cause mortality in lung transplant recipients", "glycan_involvement": "Glycosylation enhances immune evasion, contributing to pathogenicity.", "mechanism": "Spike glycoprotein enables infection, leading to increased mortality in immunosuppressed LTRs.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12133828" }, { "confidence": "medium", "disease": "All-cause mortality in lung transplant recipients", "glycan_involvement": "Therapeutic antibody glycosylation affects effector function and clearance.", "mechanism": "Prior alemtuzumab therapy associated with increased mortality post-SARS-CoV-2 infection.", "protein": "Alemtuzumab (anti-CD52 antibody, glycoprotein therapeutic)", "relationship_type": "biomarker/causal (risk factor)", "source_pmcid": "PMC12133828" }, { "confidence": "low", "disease": "Chronic Lung Allograft Dysfunction (CLAD)", "glycan_involvement": "Glycosylation may affect chronic immune activation.", "mechanism": "Spike-mediated infection may contribute to chronic allograft dysfunction; limited evidence.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (potential, not confirmed)", "source_pmcid": "PMC12133828" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for VCAM-1 stability and function in cell adhesion.", "mechanism": "SAB suppresses TNF-\u03b1-induced VCAM-1 expression via NF-\u03baB pathway, reducing leukocyte adhesion and vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ICAM-1 adhesive properties.", "mechanism": "SAB and SAA downregulate ICAM-1 expression, inhibiting monocyte adhesion and endothelial inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation critical for CD31-mediated cell-cell interactions.", "mechanism": "SAA preserves CD31 expression via HIF1\u03b1/HSF1/CD31 pathway, maintaining endothelial barrier integrity.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "protective", "source_pmcid": "PMC12133847" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation affects VE-cadherin adhesive function.", "mechanism": "DSS and SAB attenuate VE-cadherin phosphorylation, stabilizing endothelial junctions and reducing permeability.", "protein": "VE-cadherin", "relationship_type": "protective", "source_pmcid": "PMC12133847" }, { "confidence": "high", "disease": "Plaque instability", "glycan_involvement": "Glycosylation influences MMP-9 secretion and activity.", "mechanism": "SAA and SAB suppress MMP-9 production, preventing extracellular matrix degradation and plaque rupture.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for LOX-1 ligand binding.", "mechanism": "SAB inhibits LOX-1-mediated ox-LDL uptake, reducing endothelial apoptosis and inflammation.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ABCA1 trafficking and function.", "mechanism": "SAB and RA upregulate ABCA1, enhancing cholesterol efflux from macrophages and reducing foam cell formation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12133847" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects CD36 ligand binding and surface expression.", "mechanism": "SAB acts as a CD36 antagonist, inhibiting ox-LDL uptake and foam cell formation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "medium", "disease": "Plaque instability", "glycan_involvement": "Glycosylation required for MerTK receptor function.", "mechanism": "PCA upregulates MerTK via miR-10b/KLF4 axis, enhancing macrophage efferocytosis and reducing necrotic core expansion.", "protein": "MerTK", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological proce", "gene_name": "MERTK", "glycan_count": 28, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G62461SM", "G10486CT", "G11629QQ", "G37399XV", "G59626AS", "G65184UU", "G80920RR", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX", "G56784JY", "G57888GL", "G62765YT", "G02815KT", "G23010ZW", "G02030ZB", "G10019LZ", "G12580WI", "G15169WU", "G22310AV", "G38663NM", "G52527GH", "G83460ZZ", "G84452RH", "G06356OH", "G29068FM", "G43417UB" ], "uniprot_id": "Q12866" }, "relationship_type": "protective", "source_pmcid": "PMC12133847" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates chemokine-receptor interactions.", "mechanism": "DSS increases SDF-1\u03b1/CXCR4 signaling, promoting EPC migration and vascular repair.", "protein": "SDF-1\u03b1 (CXCL12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133847" }, { "confidence": "high", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Direct inhibition of glycan polymerization in cell wall glycoproteins.", "mechanism": "Caspofungin inhibits \u03b2-(1,3)-D-glucan synthesis in fungal cell walls, disrupting fungal integrity and treating IPA.", "protein": "\u03b2-(1,3)-D-glucan", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133850" }, { "confidence": "high", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Indirect; ergosterol biosynthetic enzymes may be glycosylated, affecting membrane structure.", "mechanism": "Voriconazole inhibits ergosterol synthesis, affecting fungal membrane glycoproteins and killing Aspergillus.", "protein": "Ergosterol biosynthetic enzymes", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133850" }, { "confidence": "high", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Galactomannan is a glycosylated secreted protein detected in patient samples.", "mechanism": "Galactomannan is released by Aspergillus and used for IPA diagnosis.", "protein": "Galactomannan", "relationship_type": "biomarker", "source_pmcid": "PMC12133850" }, { "confidence": "medium", "disease": "Pancytopenia", "glycan_involvement": "Altered glycan exposure may affect immune cell function.", "mechanism": "Caspofungin therapy associated with increased risk of pancytopenia, possibly via immune modulation.", "protein": "\u03b2-(1,3)-D-glucan", "relationship_type": "causal (adverse drug reaction)", "source_pmcid": "PMC12133850" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Potential impact on host glycoprotein metabolism.", "mechanism": "Voriconazole therapy can cause liver toxicity, possibly via off-target effects on host glycoproteins.", "protein": "Ergosterol biosynthetic enzymes", "relationship_type": "causal (adverse drug reaction)", "source_pmcid": "PMC12133850" }, { "confidence": "medium", "disease": "Renal dysfunction", "glycan_involvement": "Possible immune-mediated effects via glycan recognition.", "mechanism": "Caspofungin therapy associated with renal toxicity in some patients.", "protein": "\u03b2-(1,3)-D-glucan", "relationship_type": "causal (adverse drug reaction)", "source_pmcid": "PMC12133850" }, { "confidence": "high", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Glycosylation is essential for antigenicity and detection.", "mechanism": "Detection of galactomannan in serum or BAL fluid aids IPA diagnosis.", "protein": "Galactomannan", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12133850" }, { "confidence": "high", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Glycan structure is detected in diagnostic assays.", "mechanism": "Elevated \u03b2-(1,3)-D-glucan levels indicate fungal infection.", "protein": "\u03b2-(1,3)-D-glucan", "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12133850" }, { "confidence": "medium", "disease": "Pancytopenia", "glycan_involvement": "Immune recognition of glycosylated fungal antigens may contribute.", "mechanism": "Combination antifungal therapy increases risk of pancytopenia, possibly via immune response to fungal glycoproteins.", "protein": "Galactomannan", "relationship_type": "causal (adverse drug reaction)", "source_pmcid": "PMC12133850" }, { "confidence": "medium", "disease": "Invasive Pulmonary Aspergillosis (IPA)", "glycan_involvement": "Glycosylation may affect enzyme stability and drug sensitivity.", "mechanism": "Voriconazole targeting ergosterol biosynthesis protects against IPA progression.", "protein": "Ergosterol biosynthetic enzymes", "relationship_type": "protective", "source_pmcid": "PMC12133850" }, { "confidence": "high", "disease": "Hodgkin\u2019s lymphoma", "glycan_involvement": "CD30 is a heavily glycosylated cell surface protein; glycosylation affects antibody binding and signaling.", "mechanism": "CD30 is highly expressed on Reed-Sternberg cells in cHL and is targeted by brentuximab vedotin.", "protein": "CD30", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12133851" }, { "confidence": "high", "disease": "Hodgkin\u2019s lymphoma", "glycan_involvement": "CD15 is a carbohydrate antigen (Lewis x); glycosylation is essential for its detection.", "mechanism": "CD15 is expressed on Reed-Sternberg cells and used for diagnostic immunophenotyping.", "protein": "CD15", "relationship_type": "biomarker", "source_pmcid": "PMC12133851" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "Altered glycosylation may increase immune recognition and cytotoxicity.", "mechanism": "T-cell mediated cytotoxicity against biliary epithelial glycoproteins leads to ductopenia.", "protein": "Biliary epithelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133851" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "Glycosylation of CD30 affects BV binding and efficacy.", "mechanism": "BV targets CD30+ lymphoma cells, reducing paraneoplastic cytokine release and reversing VBDS.", "protein": "Brentuximab vedotin target (CD30)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12133851" }, { "confidence": "medium", "disease": "Autoimmune hepatitis (SSA positive)", "glycan_involvement": "SSA is a glycoprotein; glycosylation may affect autoantigenicity.", "mechanism": "Elevated SSA IgG may indicate autoimmune involvement in hepatic injury.", "protein": "SSA (Ro60)", "relationship_type": "biomarker", "source_pmcid": "PMC12133851" }, { "confidence": "high", "disease": "Intrahepatic cholestasis", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Elevated GGT reflects cholestatic liver injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133851" }, { "confidence": "high", "disease": "Intrahepatic cholestasis", "glycan_involvement": "ALP glycosylation modulates enzyme activity and serum levels.", "mechanism": "Elevated ALP is a marker of bile duct injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133851" }, { "confidence": "medium", "disease": "Hodgkin\u2019s lymphoma", "glycan_involvement": "Potential glycosylation may affect stability and nuclear localization.", "mechanism": "PAX5 is expressed in B-cell lineage and used for lymphoma diagnosis.", "protein": "PAX5", "protein_enriched": { "function": "Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:10811620, PubMed:27181361). Fulfills a dual role by repressing B-lineage ina", "gene_name": "PAX5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02548" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133851" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "TGR5 glycosylation affects receptor function and cell surface expression.", "mechanism": "UDCA acts via TGR5 to protect biliary epithelial cells and promote bile flow.", "protein": "Ursodeoxycholic acid receptor (TGR5)", "relationship_type": "protective", "source_pmcid": "PMC12133851" }, { "confidence": "medium", "disease": "Drug-induced liver injury", "glycan_involvement": "Drug-induced changes in glycosylation may increase susceptibility to injury.", "mechanism": "Celecoxib and chemotherapy may damage glycoproteins on biliary epithelial cells, contributing to VBDS.", "protein": "Biliary epithelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12133851" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CD147 is a highly glycosylated protein; glycosylation is essential for its function and cell surface expression.", "mechanism": "Elevated CD147 promotes tumor aggressiveness, chromosomal instability, and poor prognosis via MAPK/ERK, PI3K/Akt, and MMP activation.", "protein": "CD147 (EMMPRIN)", "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "ICAM1 is N-glycosylated; glycosylation modulates ligand binding and cell-cell interactions.", "mechanism": "ICAM1 mediates cell adhesion, leukocyte migration, and is associated with tumor invasion and metastasis.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "RET is N-glycosylated; glycosylation is required for proper folding and receptor function.", "mechanism": "RET/PTC rearrangements drive PTC initiation and progression via constitutive kinase activation and MAPK pathway signaling.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CSF2 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "CSF2 is associated with poor prognosis, promoting myeloid cell development and tumor progression in the microenvironment.", "protein": "CSF2", "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CXCL5 is glycosylated; glycosylation may influence secretion and receptor interaction.", "mechanism": "CXCL5 promotes angiogenesis and tumor progression; high expression correlates with high-risk PTC.", "protein": "CXCL5", "protein_enriched": { "function": "Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes", "gene_name": "CXCL5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CD40LG is glycosylated; glycosylation may affect receptor binding.", "mechanism": "CD40LG expression correlates with prognosis; CD40LG-CD40 interaction inhibits tumor proliferation and activates immune response.", "protein": "CD40LG", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CCL17 is glycosylated; glycosylation may affect chemokine activity.", "mechanism": "CCL17 is associated with tumor angiogenesis and progression; high levels indicate high-risk PTC.", "protein": "CCL17", "protein_enriched": { "function": "Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes. Therefore plays an important role in a wide range of inflammatory and imm", "gene_name": "CCL17", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92583" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma (PTC)", "glycan_involvement": "CCL19 is glycosylated; glycosylation may modulate function.", "mechanism": "CCL19 is linked to tumor progression and immune cell recruitment; high expression marks high-risk PTC.", "protein": "CCL19", "protein_enriched": { "function": "May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell ", "gene_name": "CCL19", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99731" }, "relationship_type": "biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Poorly differentiated thyroid carcinoma (PDTC)", "glycan_involvement": "N-glycosylation required for RET function.", "mechanism": "RET/PTC rearrangements are more frequent in aggressive subtypes, contributing to dedifferentiation.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "medium", "disease": "Anaplastic thyroid carcinoma (ATC)", "glycan_involvement": "N-glycosylation required for RET function.", "mechanism": "RET/PTC rearrangements contribute to tumorigenesis in undifferentiated thyroid cancers.", "protein": "RET", "protein_enriched": { "function": "Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-deri", "gene_name": "RET", "glycan_count": 4, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G78959FJ", "G62765YT", "G43223CG", "G31852PQ" ], "uniprot_id": "P07949" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12133868" }, { "confidence": "high", "disease": "Spinal and Bulbar Muscular Atrophy (SBMA)", "glycan_involvement": "Glycosylation may affect AR stability and localization.", "mechanism": "CAG expansion in AR gene leads to mutant AR; androgen interaction with mutant AR drives disease.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Glycosylation may modulate AR signaling in neurons.", "mechanism": "Loss of AR function at spinal motor neurons increases axonal vulnerability.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "causal", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Duchenne Muscular Dystrophy (DMD)", "glycan_involvement": "Glycosylation may affect AR receptor-ligand interactions.", "mechanism": "AR activation improves muscle strength and reduces adipose infiltration.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134011" }, { "confidence": "high", "disease": "Alzheimer Disease (AD)", "glycan_involvement": "APP glycosylation regulates amyloid beta production.", "mechanism": "Low androgen levels increase amyloid beta deposition and reduce hippocampal volume.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Parkinson Disease (PD)", "glycan_involvement": "Glycosylation may influence AR function in dopaminergic neurons.", "mechanism": "Androgen deficiency associated with higher PD risk; AR signaling may be neuroprotective.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "protective", "source_pmcid": "PMC12134011" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MOG is highly glycosylated; glycan structures modulate immune recognition.", "mechanism": "Testosterone promotes remyelination via AR signaling in oligodendrocytes.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Migraine", "glycan_involvement": "CGRP glycosylation affects receptor binding and activity.", "mechanism": "Androgens modulate neuroinflammation via CGRP and non-CGRP pathways.", "protein": "Calcitonin Gene-Related Peptide (CGRP)", "protein_enriched": { "function": "CGRP1/CALCA is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex (PubMed:1318039, PubMed:33602864, PubMed:9620797). Dilates a variety of vessels including the c", "gene_name": "CALCA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06881" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Cluster Headache", "glycan_involvement": "Glycosylation may regulate AR function in hypothalamic neurons.", "mechanism": "TRT alleviates refractory cluster headache in hypogonadal men.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "protective", "source_pmcid": "PMC12134011" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation may affect AR localization in neuronal membranes.", "mechanism": "Androgens exert antiseizure effects, possibly via AR-mediated modulation of neurotransmitter systems.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "protective", "source_pmcid": "PMC12134011" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)", "glycan_involvement": "N-glycosylation of MOG modulates immune response.", "mechanism": "MOG is the autoantigen in MOGAD; glycosylation affects antibody recognition.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12134011" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Palmitoylation and nitrosylation at Cys156; glycosylation not directly discussed.", "mechanism": "Cys156 oxidation and reduced abundance in tumor tissue; interacts with oncogenic SRC signaling.", "protein": "Caveolin-1 (CAV1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation site mentioned; general glycoprotein.", "mechanism": "Cys240 oxidation in tumors; interacts with PKC and SRC, modulating oncogenic pathways.", "protein": "RACK1", "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Cys139 oxidation reduces activity; downregulation impairs methylglyoxal detoxification.", "protein": "Glyoxalase 1 (GLO1)", "protein_enriched": { "function": "Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294). Involved in the regulation of TNF-indu", "gene_name": "GLO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q04760" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134105" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Reduced protein abundance and less oxidized Cys201 in tumors; low expression correlates with poor survival.", "protein": "Glyoxalase 2 (GLO2/HAGH)", "protein_enriched": { "function": "Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanetiol (MTMT) (By similarity). Also binds odorants acetophenone and benzalde", "gene_name": "OR2C1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O95371" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Increased abundance and oxidation at Cys247; regulates methylglyoxal production and glyoxalase system.", "protein": "Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134105" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Oxidation at Cys49 and Cys326; increased abundance may compensate for oxidative damage.", "protein": "Pyruvate kinase M2 (PKM2)", "protein_enriched": { "function": "Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618-1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Oxidation at Cys170; may reduce glycolytic activity and reroute metabolism.", "protein": "Phosphofructokinase (PFK)", "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Oxidation at Cys379/380; may affect glycolytic flux and antioxidant production.", "protein": "Phosphoglycerate kinase 1 (PGK1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Less oxidized at Cys339 and more abundant in tumors; supports cancer survival and metastasis.", "protein": "Aldolase A (ALDOA)", "relationship_type": "biomarker", "source_pmcid": "PMC12134105" }, { "confidence": "high", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "No specific glycosylation site mentioned; general glycoprotein.", "mechanism": "Upregulated in tumors; increases glutathione biosynthesis for antioxidative defense.", "protein": "Glutathione synthase (GSS)", "relationship_type": "protective", "source_pmcid": "PMC12134105" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Extensive N-glycosylation shields Env from immune recognition.", "mechanism": "Env mediates viral entry and is the sole neutralizing antibody target.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycan shielding limits antibody access; stabilization and glycan engineering may improve immunogenicity.", "mechanism": "Env is targeted by vaccine-induced neutralizing antibodies.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation modulates antigenicity and immune evasion.", "mechanism": "HA is the main target of neutralizing antibodies and vaccines.", "protein": "Influenza virus Hemagglutinin (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects spike conformation and immune recognition.", "mechanism": "Spike is the principal target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycan-dependent epitopes are recognized by broadly neutralizing antibodies.", "mechanism": "Env-specific antibodies indicate exposure and immune response.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC12134134" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Some bNAbs target glycan-dependent epitopes (e.g., N301, N332).", "mechanism": "Broadly neutralizing antibodies targeting Env can confer protection.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "protective", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Stabilization reduces gp120 shedding and preserves glycan shield.", "mechanism": "Stabilized Env trimers (SOSIP, NFL-TD) are used as vaccine immunogens.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Native glycosylation state may be better preserved in host cell expression.", "mechanism": "Replicating viral vectors expressing Env induce more durable neutralizing antibody responses.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "May overcome glycan-mediated immune evasion by increasing antigen persistence.", "mechanism": "High-dose and dose-escalation regimens improve durability of Env-specific antibody responses.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "No direct glycan modification, but may affect immune response to glycan-shielded epitopes.", "mechanism": "TLR stimulation (adjuvants, RNA40) modestly enhances Env immunogenicity.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134134" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "C3 is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Upregulated in astrocytes during neuroinflammation; contributes to synaptic dysfunction.", "protein": "C3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134135" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 glycosylation modulates secretion and receptor binding.", "mechanism": "IL-6 is upregulated in astrocytes during inflammatory response; drives neuroinflammatory cascades.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134135" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "TNF glycosylation influences stability and activity.", "mechanism": "TNF-alpha upregulation in astrocytes promotes neuroinflammatory damage.", "protein": "TNF (TNF-alpha)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation regulates chaperone activity and ER localization.", "mechanism": "Induced by caloric restriction; maintains mitochondrial function and reduces cytokine production.", "protein": "HSPA5 (GRP78)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Potential glycosylation may affect mitochondrial targeting.", "mechanism": "Supports mitochondrial respiration and DNA methylation; knockdown increases inflammatory cytokines.", "protein": "SHMT2", "protein_enriched": { "function": "Has an essential role in spermatogenesis (PubMed:36150389). It is required to repress transposable elements and prevent their mobilization, which is essential for the germline integrity (By similarity", "gene_name": "FKBP6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O75344" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Regulates amino acid transport under metabolic stress; supports astrocyte metabolism.", "protein": "SLC3A2", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Chronic neurodegenerative diseases", "glycan_involvement": "Glycosylation modulates ER retention and activity.", "mechanism": "Protein folding and stress response; upregulated under metabolic stress.", "protein": "PDIA6", "protein_enriched": { "function": "May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, whi", "gene_name": "PDIA6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15084" }, "relationship_type": "protective", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Astrogliosis", "glycan_involvement": "Glycosylation may affect filament assembly.", "mechanism": "Marker of reactive astrocytes; upregulated during neuroinflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates chemokine gradient formation.", "mechanism": "Chemokine upregulated in astrocytes; recruits immune cells to CNS.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134135" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "Chemokine involved in immune cell recruitment; upregulated in astrocytes during inflammation.", "protein": "CCL4", "protein_enriched": { "function": "Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of ", "gene_name": "CCL4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13236" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134135" }, { "confidence": "high", "disease": "Aging-associated organ decline", "glycan_involvement": "No glycosylation involvement; protection is via cysteine redox regulation.", "mechanism": "ROMO1 overexpression reverses mitochondrial cysteinome oxidation, retarding functional decline in heart, muscle, liver, and brain during aging.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Cardiovascular diseases (heart failure)", "glycan_involvement": "No glycosylation involvement; mechanism is thiol protection.", "mechanism": "ROMO1 protects cysteines on heart failure driver proteins from oxidation, preserving cardiac function.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Myopathy", "glycan_involvement": "No glycosylation involvement; mechanism is cysteine redox regulation.", "mechanism": "ROMO1 upregulation prevents oxidation of muscle disease driver proteins, attenuating muscle atrophy and grip strength decline.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "No glycosylation involvement; mechanism is cysteine redox regulation.", "mechanism": "ROMO1 protects liver mitochondrial proteins from oxidation, reducing liver damage markers in aging.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "No glycosylation involvement; mechanism is cysteine redox regulation.", "mechanism": "ROMO1 upregulation reverses oxidation of brain disease driver proteins, potentially protecting against neurodegeneration.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Cell death", "glycan_involvement": "No glycosylation involvement; mechanism is via thiol redox.", "mechanism": "ROMO1 inhibits oxidative stress-induced mPTP opening and cell death via cysteine protection.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Mitochondrial dysfunction", "glycan_involvement": "No glycosylation involvement; mechanism is cysteine redox regulation.", "mechanism": "ROMO1 maintains mitochondrial respiration, Ca2+ uniport, and prevents permeability transition by protecting cysteine residues.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Oxidative stress-related pathologies", "glycan_involvement": "No glycosylation involvement; mechanism is direct ROS scavenging and thiol protection.", "mechanism": "ROMO1 detoxifies ROS and prevents irreversible cysteine oxidation in mitochondrial proteins.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "No glycosylation involvement; mechanism is indirect via mitochondrial protection.", "mechanism": "ROMO1 upregulation reduces aging-associated inflammation markers (monocytes, neutrophils, IL-6).", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "No glycosylation involvement; mechanism is via cysteine redox.", "mechanism": "General association: dysregulation of protein oxidations (including mitochondrial cysteinome) is linked to diabetes.", "protein": "ROMO1", "protein_enriched": { "function": "Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translo", "gene_name": "TIMM10B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J6" }, "relationship_type": "protective", "source_pmcid": "PMC12134242" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects enzyme stability and activity; inhibitors may interact with glycan moieties.", "mechanism": "Inhibition of \u03b1-amylase reduces carbohydrate hydrolysis, lowering postprandial blood glucose.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134304" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates substrate specificity and inhibitor binding.", "mechanism": "Inhibition of \u03b1-glucosidase delays glucose absorption, controlling hyperglycemia.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134304" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation influences enzyme activity and drug interaction.", "mechanism": "Similar to type 2, inhibition reduces glucose spikes.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134304" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation impacts enzyme function and inhibitor efficacy.", "mechanism": "Inhibition helps manage blood glucose levels.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134304" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects AChE folding, localization, and inhibitor binding.", "mechanism": "AChE inhibition increases acetylcholine levels, improving cognitive function.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134304" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation changes may modulate enzyme activity in diabetes.", "mechanism": "AChE activity is altered in diabetes, reflecting metabolic dysfunction.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134304" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may influence cross-talk between metabolic and neurodegenerative processes.", "mechanism": "Shared metabolic pathways link \u03b1-glucosidase activity to neurodegeneration.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134304" }, { "confidence": "low", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation status may reflect disease state.", "mechanism": "Altered carbohydrate metabolism in AD may involve \u03b1-amylase.", "protein": "\u03b1-amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12134304" }, { "confidence": "medium", "disease": "Type 3 Diabetes (Alzheimer's Disease)", "glycan_involvement": "Glycosylation may modulate AChE function in neurodegeneration.", "mechanism": "Impaired insulin signaling and cholinergic dysfunction are linked in AD.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "causal", "source_pmcid": "PMC12134304" }, { "confidence": "low", "disease": "Type 3 Diabetes (Alzheimer's Disease)", "glycan_involvement": "Glycosylation may affect enzyme activity in the brain.", "mechanism": "Insulin resistance and altered glucose metabolism contribute to AD pathology.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "causal", "source_pmcid": "PMC12134304" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "LCN2 is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "STAT3-activated LCN2 secreted by N2-neutrophils triggers MET of tumor cells, facilitating colonization and metastatic expansion.", "protein": "Lipocalin 2 (LCN2)", "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "PD-L1 glycosylation modulates its stability and immune checkpoint function.", "mechanism": "Upregulated by GM-CSF/STAT5/aryl hydrocarbon receptor axis in lung macrophages, promoting Treg differentiation and immunosuppressive PMN.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "S100A8 is glycosylated; glycosylation may affect its chemotactic activity.", "mechanism": "Induced by VEGF-\u03b1, promotes infiltration of Mac1+ myeloid cells and immunosuppressive PMN.", "protein": "S100A8", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "Glycosylation may modulate S100A9's interaction with receptors.", "mechanism": "Promotes myeloid cell accumulation and chemoattractant secretion, facilitating PMN and metastasis.", "protein": "S100A9", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134401" }, { "confidence": "medium", "disease": "Lung metastasis", "glycan_involvement": "SAA3 is glycosylated; glycosylation may affect its inflammatory activity.", "mechanism": "Induced by S100A8/A9 and IL-1\u03b2, activates NF-\u03baB signaling, increases MMP9, and promotes HCC pulmonary metastasis.", "protein": "Serum Amyloid A3 (SAA3)", "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "Versican is a proteoglycan with extensive glycosylation; glycan chains mediate ECM interactions.", "mechanism": "Expressed by myeloid cells in metastatic lung, promotes MET and accelerates metastasis.", "protein": "Versican", "protein_enriched": { "function": "May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "medium", "disease": "Salivary adenoid cystic carcinoma (SACC) lung metastasis", "glycan_involvement": "E-cadherin glycosylation affects cell adhesion and EMT.", "mechanism": "Epiregulin upregulation induces EMT via GLI1/E-cadherin regulation, promoting metastasis.", "protein": "E-cadherin (CDH1)", "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "medium", "disease": "SACC lung metastasis", "glycan_involvement": "Epiregulin is glycosylated; glycosylation may affect receptor binding.", "mechanism": "Induces EMT and enhances metastatic potential via GLI1/E-cadherin pathway.", "protein": "Epiregulin", "protein_enriched": { "function": "Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation (PubMed:9419975). Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regu", "gene_name": "EREG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O14944" }, "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Lung metastasis", "glycan_involvement": "Fibronectin glycosylation modulates ECM assembly and cell adhesion.", "mechanism": "LOXL2 upregulates fibronectin in lung fibroblasts, supporting PMN formation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "Postoperative metastasis", "glycan_involvement": "LOXL2 is glycosylated; glycosylation may affect enzymatic activity.", "mechanism": "Remodels ECM, increases tissue stiffness, recruits BMDCs, and promotes metastasis; LOX inhibition reduces metastasis.", "protein": "LOXL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134401" }, { "confidence": "high", "disease": "genetic diseases", "glycan_involvement": "O-glycosylation of capsid reduces transduction efficiency, impacting therapeutic efficacy.", "mechanism": "AAV6 capsids are used as vectors for gene therapy to treat genetic diseases.", "protein": "AAV6 capsid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134569" }, { "confidence": "high", "disease": "genetic diseases", "glycan_involvement": "Glycosylation status can affect capsid function and gene transfer efficiency.", "mechanism": "AAV capsids deliver therapeutic genes to target cells for genetic disease treatment.", "protein": "AAV capsid (general)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134569" }, { "confidence": "medium", "disease": "neuromuscular diseases", "glycan_involvement": "Capsid modifications (including glycosylation) may influence cell targeting.", "mechanism": "Engineered AAV capsids with muscle-specific tropism target muscle stem cells for gene editing.", "protein": "AAV capsid (general)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134569" }, { "confidence": "medium", "disease": "cancer", "glycan_involvement": "Capsid surface modifications (potentially including glycosylation) enable targeting.", "mechanism": "AAV capsids engineered with anti-FAP nanobodies target tumor stroma for gene delivery.", "protein": "AAV capsid (general)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134569" }, { "confidence": "high", "disease": "Retinal vascular injury", "glycan_involvement": "N-glycosylation regulates VEGFA secretion and receptor binding.", "mechanism": "VEGFA increases vascular permeability, contributing to retinal edema and vessel leakage.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Hypertensive retinopathy", "glycan_involvement": "Glycosylation may affect NLRP3 stability and inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation triggers inflammation and pyroptosis in retinal cells.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Pyroptosis", "glycan_involvement": "Glycosylation can modulate Caspase-1 activity and localization.", "mechanism": "Activated by NLRP3, Caspase-1 cleaves GSDMD and pro-IL-1\u03b2, inducing pyroptosis.", "protein": "Caspase-1", "relationship_type": "causal", "source_pmcid": "PMC12134759" }, { "confidence": "medium", "disease": "Pyroptosis", "glycan_involvement": "Potential O-glycosylation may affect membrane targeting.", "mechanism": "GSDMD cleavage forms membrane pores, leading to cell lysis and inflammation.", "protein": "GSDMD", "relationship_type": "causal", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Hypertensive retinopathy", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated IL-1\u03b2 indicates inflammasome activation and inflammation in HR.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Hypertensive retinopathy", "glycan_involvement": "N-glycosylation affects secretion and bioactivity.", "mechanism": "IL-18 is released upon inflammasome activation, marking inflammatory damage.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Hypertensive retinopathy", "glycan_involvement": "N-glycosylation modulates TNF-\u03b1 secretion.", "mechanism": "TNF-\u03b1 drives inflammation and vascular injury; ZLHXTY suppresses its expression.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134759" }, { "confidence": "medium", "disease": "Hypertensive retinopathy", "glycan_involvement": "O-glycosylation may regulate nuclear translocation.", "mechanism": "NF-\u03baB p65 mediates transcription of inflammatory genes; ZLHXTY inhibits its activation.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134759" }, { "confidence": "medium", "disease": "Retinal neurodegeneration", "glycan_involvement": "Glycosylation affects filament assembly and cell signaling.", "mechanism": "GFAP upregulation marks M\u00fcller cell activation and neuroinflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134759" }, { "confidence": "medium", "disease": "Hypertensive retinopathy", "glycan_involvement": "Glycosylation may modulate immune cell migration.", "mechanism": "Iba-1 marks microglial activation in retinal inflammation.", "protein": "Iba-1 (AIF1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134759" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Promotes activation of hepatic stellate cells, leading to ECM and collagen production.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Hydroxylation and glycosylation affect fibril formation.", "mechanism": "Major ECM component deposited during fibrosis; upregulated in NAFLD and fibrosis.", "protein": "Collagen type I (COL I)", "relationship_type": "biomarker", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not glycosylated.", "mechanism": "Marker of activated hepatic stellate cells in fibrotic tissue.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Pro-inflammatory cytokine upregulated in NAFLD and fibrosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "Glycosylation modulates activity and stability.", "mechanism": "Early-phase pro-inflammatory cytokine elevated in NAFLD.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Late-phase pro-inflammatory cytokine elevated in NAFLD.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12134770" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "N-glycosylation affects half-life and function.", "mechanism": "Serum albumin levels decrease with liver dysfunction.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12134770" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Heavily glycosylated; glycosylation modulates cell adhesion.", "mechanism": "Endothelial marker; altered expression in fibrotic tissue.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134770" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Not glycosylated.", "mechanism": "Activation by nicotinamide/NAD+ reduces inflammation and fibrosis.", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134770" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation affects assembly and activity.", "mechanism": "Generates ROS, contributing to oxidative stress in NAFLD.", "protein": "NADPH oxidase", "relationship_type": "causal", "source_pmcid": "PMC12134770" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Dkk3 is a secreted glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Dkk3 activates FoxO3, promoting transcription of Fbxo32 and Murf1, leading to muscle atrophy.", "protein": "Dkk3", "relationship_type": "causal", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Glucocorticoid-induced muscle atrophy", "glycan_involvement": "Glycosylation of Dkk3 likely required for its extracellular function.", "mechanism": "Dkk3 upregulation by dexamethasone enhances FoxO3/Fbxo32/Murf1 pathway, driving muscle protein degradation.", "protein": "Dkk3", "relationship_type": "causal", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Skeletal muscle atrophy", "glycan_involvement": "Glycosylation status may influence Dkk3's activity as a therapeutic target.", "mechanism": "Knockdown or downregulation of Dkk3 protects against muscle atrophy by suppressing FoxO3/Fbxo32/Murf1 axis.", "protein": "Dkk3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Indirect; ZBED6 regulates glycoprotein Dkk3 transcription.", "mechanism": "ZBED6 knockout downregulates Dkk3, reducing activation of atrophy pathways and increasing muscle mass.", "protein": "ZBED6", "protein_enriched": { "function": "Ethanolaminephosphotransferase that catalyzes the transfer of phosphoethanolamine (PE) from CDP-ethanolamine to lipid acceptors, the final step in the synthesis of PE via the 'Kennedy' pathway (PubMed", "gene_name": "SELENOI", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9C0D9" }, "relationship_type": "protective", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Glucocorticoid-induced muscle atrophy", "glycan_involvement": "Indirect; ZBED6 modulates Dkk3 glycoprotein levels.", "mechanism": "ZBED6 knockout prevents dexamethasone-induced muscle atrophy via suppression of Dkk3-Fbxo32 axis.", "protein": "ZBED6", "protein_enriched": { "function": "Ethanolaminephosphotransferase that catalyzes the transfer of phosphoethanolamine (PE) from CDP-ethanolamine to lipid acceptors, the final step in the synthesis of PE via the 'Kennedy' pathway (PubMed", "gene_name": "SELENOI", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9C0D9" }, "relationship_type": "protective", "source_pmcid": "PMC12134784" }, { "confidence": "medium", "disease": "Obesity-induced muscle atrophy", "glycan_involvement": "Glycosylation may affect Dkk3's metabolic regulatory functions.", "mechanism": "Dkk3 is essential for glucose homeostasis; its upregulation may contribute to muscle wasting in obesity.", "protein": "Dkk3", "relationship_type": "causal", "source_pmcid": "PMC12134784" }, { "confidence": "medium", "disease": "Type 2 diabetes-induced muscle atrophy", "glycan_involvement": "Glycosylation may modulate Dkk3's activity in metabolic disease.", "mechanism": "Dkk3's role in glucose homeostasis links it to muscle atrophy in T2D.", "protein": "Dkk3", "relationship_type": "causal", "source_pmcid": "PMC12134784" }, { "confidence": "medium", "disease": "Muscular dystrophy", "glycan_involvement": "Glycosylation may influence Dkk3's biomarker potential.", "mechanism": "Dkk3 expression correlates with muscle atrophy and regeneration defects.", "protein": "Dkk3", "relationship_type": "biomarker", "source_pmcid": "PMC12134784" }, { "confidence": "medium", "disease": "Sepsis-induced muscle atrophy", "glycan_involvement": "Glycosylation required for Dkk3 secretion and function.", "mechanism": "Dkk3 upregulation promotes atrophy via FoxO3/Fbxo32/Murf1 pathway.", "protein": "Dkk3", "relationship_type": "causal", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Skeletal muscle atrophy", "glycan_involvement": "Glycosylation may affect detectability and stability as a biomarker.", "mechanism": "Elevated Dkk3 levels indicate activation of muscle atrophy pathways.", "protein": "Dkk3", "relationship_type": "biomarker", "source_pmcid": "PMC12134784" }, { "confidence": "high", "disease": "Diabetes Insipidus (Central)", "glycan_involvement": "ADH is glycosylated, which affects its stability and secretion.", "mechanism": "Deficiency of ADH secretion due to pituitary injury leads to central DI.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "causal", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Diabetes Insipidus (Central)", "glycan_involvement": "Desmopressin is a glycopeptide; glycosylation enhances its stability and bioactivity.", "mechanism": "Desmopressin acts as an ADH analog to replace deficient hormone and control polyuria.", "protein": "Desmopressin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134826" }, { "confidence": "medium", "disease": "Diabetes Insipidus (Central)", "glycan_involvement": "Oxytocin is glycosylated, which may affect receptor binding and function.", "mechanism": "Oxytocin, structurally similar to vasopressin, can exert antidiuretic effects in DI.", "protein": "Oxytocin", "protein_enriched": { "function": "Neurophysin 1 specifically binds oxytocin", "gene_name": "OXT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01178" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Rathke\u2019s cleft cyst", "glycan_involvement": "Glycosylation of ADH is required for proper secretion; disruption may worsen deficiency.", "mechanism": "RCC compresses pituitary, impairing ADH secretion and causing central DI.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "causal", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Hypernatremia", "glycan_involvement": "Glycosylation affects ADH stability and function.", "mechanism": "ADH deficiency leads to excessive water loss, resulting in hypernatremia.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "causal", "source_pmcid": "PMC12134826" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation of pituitary hormones affects their secretion.", "mechanism": "Pituitary dysfunction can cause multiple hormonal deficiencies including ADH and TSH.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "biomarker", "source_pmcid": "PMC12134826" }, { "confidence": "medium", "disease": "Hypocortisolism", "glycan_involvement": "Glycosylation is important for pituitary hormone stability.", "mechanism": "Pituitary injury may impair ACTH and ADH secretion.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "biomarker", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Hypernatremia", "glycan_involvement": "Glycosylation enhances desmopressin\u2019s pharmacokinetics.", "mechanism": "Desmopressin reduces urine output, helping correct hypernatremia.", "protein": "Desmopressin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Diabetes Insipidus (Central)", "glycan_involvement": "Glycosylation status may affect ADH measurement.", "mechanism": "Low ADH levels are diagnostic for central DI.", "protein": "Antidiuretic hormone (ADH, Vasopressin)", "relationship_type": "biomarker", "source_pmcid": "PMC12134826" }, { "confidence": "medium", "disease": "Diabetes Insipidus (Central)", "glycan_involvement": "Glycosylation may modulate oxytocin\u2019s antidiuretic effect.", "mechanism": "Oxytocin infusion temporarily reduces polyuria in DI.", "protein": "Oxytocin", "protein_enriched": { "function": "Neurophysin 1 specifically binds oxytocin", "gene_name": "OXT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01178" }, "relationship_type": "protective", "source_pmcid": "PMC12134826" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "IgG glycosylation modulates immune effector functions and autoantibody activity.", "mechanism": "Elevated serum IgG is a diagnostic marker and reflects disease activity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12134904" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting stability and receptor binding.", "mechanism": "TNF-\u03b1 mediates hepatocyte death and inflammation; targeted by infliximab.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134904" }, { "confidence": "high", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "CD20 glycosylation influences antibody binding and cell surface expression.", "mechanism": "CD20+ B cells drive autoimmunity; depletion by rituximab reduces disease activity.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "BAFF glycosylation affects receptor interaction and immune signaling.", "mechanism": "BAFF promotes B cell survival and autoantibody production; inhibition by belimumab alleviates AIH.", "protein": "B cell-activating factor (BAFF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "IL-2 glycosylation modulates receptor binding and bioactivity.", "mechanism": "Low-dose IL-2 expands Treg cells, restoring immune tolerance and reducing liver inflammation.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "C1q glycosylation is essential for complement activation and immune complex clearance.", "mechanism": "Rituximab activates C1q-mediated complement cascade for B cell depletion.", "protein": "Complement C1q", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "CD19 glycosylation affects cell signaling and antibody recognition.", "mechanism": "CD19+ B cells are expanded in AIH; MMF induces apoptosis of these cells.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "causal", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates BAFF's interaction with B cell receptors.", "mechanism": "BAFF overexpression leads to B cell expansion and autoantibody production.", "protein": "BAFF", "relationship_type": "causal", "source_pmcid": "PMC12134904" }, { "confidence": "low", "disease": "Autoimmune Hepatitis (AIH)", "glycan_involvement": "Mcl-1 glycosylation affects protein stability and anti-apoptotic function.", "mechanism": "BAFF upregulates Mcl-1, promoting B cell survival and persistence in autoimmunity.", "protein": "Mcl-1", "relationship_type": "protective", "source_pmcid": "PMC12134904" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "IgG glycosylation patterns influence autoantibody pathogenicity.", "mechanism": "Autoantibody IgG subclasses are elevated and pathogenic in SLE; sirolimus reduces IgG levels.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12134904" }, { "confidence": "high", "disease": "NAFLD-related liver fibrosis", "glycan_involvement": "None; HO-1 is not glycosylated.", "mechanism": "HO-1 induction reduces hepatic inflammation and fibrosis via SIRT1/TGF-\u03b2/Smad3 pathway modulation.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "NAFLD-related liver fibrosis", "glycan_involvement": "None; SIRT1 is not glycosylated.", "mechanism": "SIRT1 activation inhibits TGF-\u03b2/Smad3 signaling, reducing fibrogenesis.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b2 is a glycoprotein; glycosylation is required for secretion and activity.", "mechanism": "TGF-\u03b2 activates hepatic stellate cells via Smad3, promoting ECM and collagen production.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen is glycosylated; glycosylation affects fibril formation and stability.", "mechanism": "Collagen accumulation is a hallmark of fibrotic ECM deposition.", "protein": "Type I collagen", "relationship_type": "causal", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "None; \u03b1-SMA is not glycosylated.", "mechanism": "\u03b1-SMA marks activated hepatic stellate cells in fibrotic tissue.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "None; Smad3 is not glycosylated.", "mechanism": "Smad3 transduces TGF-\u03b2 signals, driving fibrogenic gene expression.", "protein": "Smad3", "protein_enriched": { "function": "Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194).", "gene_name": "SMAD5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99717" }, "relationship_type": "causal", "source_pmcid": "PMC12134905" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "None; HO-1 is not glycosylated.", "mechanism": "Serum HO-1 levels are elevated in NAFLD and correlate with disease severity.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134905" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "None; SIRT1 is not glycosylated.", "mechanism": "SIRT1 activation improves hepatic lipid metabolism and reduces steatosis.", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation required for TGF-\u03b2 function.", "mechanism": "TGF-\u03b2 signaling drives progression from steatosis to fibrotic NASH.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12134905" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Collagen glycosylation affects matrix architecture.", "mechanism": "Excess collagen deposition leads to cirrhotic scarring.", "protein": "Type I collagen", "relationship_type": "causal", "source_pmcid": "PMC12134905" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "TM6SF2 is a glycoprotein; glycosylation may affect its stability and function in lipid metabolism.", "mechanism": "Intestinal depletion of TM6SF2 exacerbates HFD-induced liver lipid accumulation and injury via gut-liver axis.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12134907" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation may modulate TM6SF2 trafficking and function.", "mechanism": "TM6SF2 E167K variant increases risk of NASH by promoting hepatic lipid retention and impairing VLDL export.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12134907" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "Potential impact of glycosylation on TM6SF2-mediated lipid export.", "mechanism": "TM6SF2 deficiency leads to increased hepatic triglyceride accumulation.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12134907" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation status may influence TM6SF2 function in hepatocytes.", "mechanism": "TM6SF2 knockout increases serum ALT/AST, indicating aggravated liver injury.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12134907" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "LPC is a glycophospholipid; altered metabolism reflects glycan pathway dysregulation.", "mechanism": "Elevated serum LPC (18:0/0:0) in TM6SF2 GKO mice under HFD is associated with MASLD exacerbation.", "protein": "LPC (18:0/0:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12134907" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "SM is a glycosphingolipid; changes indicate glycan pathway involvement in disease.", "mechanism": "Downregulated sphingomyelin signaling pathway in TM6SF2 GKO-HFD mice correlates with MASLD severity.", "protein": "SM (d18:1/20:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12134907" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycophospholipid metabolism altered in disease.", "mechanism": "Upregulated in TM6SF2 GKO-HFD mice; correlates with MASLD progression.", "protein": "1-O-Hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC12134907" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Reflects altered glycolipid metabolism.", "mechanism": "Elevated in TM6SF2 GKO-HFD mice; correlates with MASLD severity.", "protein": "Oleoylcarnitine", "relationship_type": "biomarker", "source_pmcid": "PMC12134907" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect TM6SF2's interaction with microbiota and barrier function.", "mechanism": "TM6SF2 regulates gut microbiota composition and intestinal permeability, impacting MASLD progression.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134907" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Proper glycosylation may be required for TM6SF2's protective function.", "mechanism": "Wild-type TM6SF2 protects against HFD-induced liver lipid accumulation and injury.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "protective", "source_pmcid": "PMC12134907" }, { "confidence": "high", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "FABP3 upregulation promotes sorafenib resistance by facilitating fatty acid transport to lipid droplets, reducing ROS-induced cell death.", "protein": "FABP3", "relationship_type": "causal", "source_pmcid": "PMC12134909" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "FABP3 is highly expressed in HCC, especially HBV-related cases, and correlates with poor prognosis.", "protein": "FABP3", "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "high", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Inhibition or knockdown of FABP3 restores sorafenib sensitivity and induces apoptosis in resistant HCC cells.", "protein": "FABP3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "E-cadherin is a glycoprotein; glycosylation affects cell adhesion, but not specifically discussed here.", "mechanism": "Downregulated in resistant HCC; upregulated upon FABP3 inhibition or OA treatment, indicating reversal of EMT.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "N-cadherin is a glycoprotein; glycosylation affects function, but not specifically discussed here.", "mechanism": "Upregulated in resistant HCC; downregulated upon FABP3 inhibition or OA treatment, indicating EMT involvement.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Upregulated in resistant HCC; downregulated by FABP3 inhibition or OA, mediating EMT and invasiveness.", "protein": "Snail", "protein_enriched": { "function": "Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration (PubMed:10655587, PubMed:15647282, ", "gene_name": "SNAI1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95863" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Promotes HCC cell migration and invasion via PI3K/AKT/Snail pathway.", "protein": "FABP3", "relationship_type": "causal", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "PARP1 is a glycoprotein; glycosylation not discussed here.", "mechanism": "Cleaved PARP1 increases upon FABP3 inhibition, indicating apoptosis in resistant cells.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "Sorafenib-resistant HCC", "glycan_involvement": "Caspase-3 is not a classical glycoprotein; glycosylation not discussed.", "mechanism": "Cleaved Caspase-3 increases upon FABP3 inhibition, indicating apoptosis in resistant cells.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "medium", "disease": "HBV-related HCC", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "FABP3 is highly expressed in HBV-related HCC and correlates with poor prognosis.", "protein": "FABP3", "relationship_type": "biomarker", "source_pmcid": "PMC12134909" }, { "confidence": "high", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation is essential for Pgp membrane localization and function.", "mechanism": "P-glycoprotein function affects Tc-99m MIBI uptake, aiding differentiation of benign vs malignant thyroid nodules.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation may affect TERT stability and nuclear localization.", "mechanism": "TERT mutations and telomerase activation promote cellular immortality in thyroid cancers.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134959" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation required for proper MRP1 trafficking and function.", "mechanism": "Negative correlation between Tc-99m MIBI uptake and MRP1 expression in thyroid lesions.", "protein": "MDR-associated protein-1 (MRP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "medium", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Potential glycosylation may regulate TINF2 stability.", "mechanism": "TINF2 mutations associated with altered telomere length and increased risk of PTC and melanoma.", "protein": "TINF2", "protein_enriched": { "function": "Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomera", "gene_name": "TINF2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BSI4" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Glycosylation may modulate TERT activity.", "mechanism": "TERT mutations present in 11.3% of PTC cases, associated with telomere maintenance.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Follicular thyroid carcinoma", "glycan_involvement": "Glycosylation may modulate TERT activity.", "mechanism": "TERT mutations present in 17.1% of follicular thyroid cancers.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Hurthle cell carcinoma", "glycan_involvement": "Glycosylation may modulate TERT activity.", "mechanism": "TERT mutations present in 32% of widely invasive Hurthle cell carcinomas.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Poorly differentiated thyroid cancer", "glycan_involvement": "Glycosylation may modulate TERT activity.", "mechanism": "TERT mutations present in 43.2% of poorly differentiated thyroid cancers.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Anaplastic thyroid cancer", "glycan_involvement": "Glycosylation may modulate TERT activity.", "mechanism": "TERT mutations present in 40.1% of anaplastic thyroid cancers.", "protein": "Telomerase reverse transcriptase (TERT)", "relationship_type": "biomarker", "source_pmcid": "PMC12134959" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Potential glycosylation may regulate TINF2 stability.", "mechanism": "TINF2 gene mutations associated with increased telomere length and melanoma risk.", "protein": "TINF2", "protein_enriched": { "function": "Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomera", "gene_name": "TINF2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BSI4" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12134959" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation stabilizes CEACAM6, enhancing cell adhesion and tumor progression.", "mechanism": "ALDOB-mediated lactylation increases CEACAM6 stability, promoting malignant progression.", "protein": "CEACAM6", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion and tumor progression (PubMed:10910050, PubMed:11590190, PubMed:1378450, PubMed:16204051, PubMed:2022629, PubMed:2803308, PubMed:8776764). ", "gene_name": "CEACAM6", "glycan_count": 10, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G53434XO", "G71784JC", "G92050GC", "G62765YT", "G28681TP", "G80920RR", "G57321FI" ], "uniprot_id": "P40199" }, "relationship_type": "causal", "source_pmcid": "PMC12135226" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation required for VEGFR2 function in angiogenesis.", "mechanism": "LDHA enhances lactylation of VEGFR2, increasing angiogenesis and tumor invasion.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "causal", "source_pmcid": "PMC12135226" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation modulates cell-cell adhesion in tumor vessels.", "mechanism": "LDHA-mediated lactylation increases VE-cadherin expression, promoting vasculogenic mimicry.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC12135226" }, { "confidence": "high", "disease": "Non-small cell lung cancer", "glycan_involvement": "PD-L1 glycosylation stabilizes the protein and enhances immune evasion.", "mechanism": "H3 K18 lactylation upregulates PD-L1, facilitating immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects GPR37 cell surface localization and signaling.", "mechanism": "GPR37 activates Hippo pathway, increases glycolysis and H3 K18 lactylation, promoting liver metastasis.", "protein": "GPR37", "protein_enriched": { "function": "G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation (By similarity). Acts as a receptor for sever", "gene_name": "GPR37", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G83460ZZ", "G62765YT", "G49108TO" ], "uniprot_id": "O15354" }, "relationship_type": "causal", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation required for CD39 enzymatic activity.", "mechanism": "Lactylation upregulates CD39, contributing to immunosuppression.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation stabilizes CD73 and regulates its function.", "mechanism": "Lactylation increases CD73 expression, promoting adenosine-mediated immune escape.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation modulates CCR8 ligand binding and signaling.", "mechanism": "Lactylation upregulates CCR8, facilitating tumor immune evasion.", "protein": "CCR8", "protein_enriched": { "function": "Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection", "gene_name": "CCR8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51685" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect MOESIN membrane localization.", "mechanism": "Lactylation of MOESIN enhances TGF-\u03b2 signaling in regulatory T cells, promoting carcinogenesis.", "protein": "MOESIN", "relationship_type": "causal", "source_pmcid": "PMC12135226" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may regulate METTL3 stability and function.", "mechanism": "Lactylation of METTL3 promotes m6A-mediated immunosuppression and tumor progression.", "protein": "METTL3", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, di", "gene_name": "METTL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U44" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135226" }, { "confidence": "high", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation is essential for receptor function and ligand binding.", "mechanism": "Glycoprotein IIb/IIIa inhibitors are used to prevent platelet aggregation during PCI, reducing thrombotic complications.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135292" }, { "confidence": "high", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation modulates receptor conformation and function.", "mechanism": "Inhibition of glycoprotein IIb/IIIa reduces risk of acute stent thrombosis by blocking platelet aggregation.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135292" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects receptor stability and surface expression.", "mechanism": "Glycoprotein IIb/IIIa inhibitors lower incidence of periprocedural MI during PCI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135292" }, { "confidence": "medium", "disease": "In-stent restenosis", "glycan_involvement": "Glycosylation influences receptor-ligand interactions.", "mechanism": "Inhibition may reduce platelet-driven neointimal hyperplasia, a contributor to restenosis.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135292" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "O-glycosylation essential for mucin barrier function.", "mechanism": "Reduced Muc1 expression impairs mucus layer, increasing permeability.", "protein": "Muc1", "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "O-glycosylation critical for gel-forming properties.", "mechanism": "Decreased Muc2 leads to loss of goblet cells and mucus, promoting bacterial translocation.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "Glycosylation modulates tight junction stability.", "mechanism": "Reduced Claudin2 disrupts tight junctions, increasing gut permeability.", "protein": "Claudin2", "protein_enriched": { "function": "Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an importa", "gene_name": "HDAC9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UKV0" }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "Glycosylation affects localization and function.", "mechanism": "Decreased Occludin weakens epithelial barrier.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "Glycosylation influences protein-protein interactions.", "mechanism": "Reduced ZO-1 impairs tight junction assembly.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "medium", "disease": "Colonic inflammation", "glycan_involvement": "C-type lectin domain binds bacterial glycans.", "mechanism": "Reduced Reg3\u03b2 decreases antimicrobial defense, promoting inflammation.", "protein": "Reg3\u03b2", "protein_enriched": { "function": "Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan (PubMed:16931762). ", "gene_name": "REG3A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06141" }, "relationship_type": "protective", "source_pmcid": "PMC12135405" }, { "confidence": "medium", "disease": "Colonic inflammation", "glycan_involvement": "C-type lectin domain recognizes microbial glycans.", "mechanism": "Lower Reg3\u03b3 impairs antimicrobial barrier, increasing susceptibility.", "protein": "Reg3\u03b3", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9D7L2" }, "relationship_type": "protective", "source_pmcid": "PMC12135405" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "N-glycosylation required for TLR4 surface expression and LPS binding.", "mechanism": "LPS-induced TLR4 activation triggers hepatic NF-\u03baB/NLRP3 signaling.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "Indirect; glycosylation of upstream receptors modulates activation.", "mechanism": "Activated by TLR4 signaling, NLRP3 inflammasome promotes IL-1\u03b2/IL-18 production.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12135405" }, { "confidence": "high", "disease": "Alcohol-related liver disease (ALD)", "glycan_involvement": "O-glycosylation essential for barrier function.", "mechanism": "Muc2 maintains gut barrier, limiting LPS translocation and liver injury.", "protein": "Muc2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135405" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and serum levels.", "mechanism": "Elevated GGT levels are associated with increased risk and severity of DILI in abiraterone acetate-treated patients.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Cholestatic liver injury", "glycan_involvement": "ALP glycosylation modulates its secretion and activity.", "mechanism": "ALP elevation is used to classify cholestatic type DILI via the R ratio.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Hepatocellular liver injury", "glycan_involvement": "Minor glycosylation may affect serum half-life.", "mechanism": "AST elevation indicates hepatocellular damage in DILI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Hepatocellular liver injury", "glycan_involvement": "Minor glycosylation may affect serum half-life.", "mechanism": "ALT elevation is a key marker for hepatocellular DILI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "HLA glycosylation affects antigen presentation and immune response.", "mechanism": "HLA genotype influences immune-mediated susceptibility to DILI.", "protein": "Human leukocyte antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC12135411" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Albumin glycosylation influences its stability and function.", "mechanism": "Decreased albumin may reflect impaired liver synthetic function in DILI.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "PSA glycosylation affects its detection and immunoreactivity.", "mechanism": "PSA levels are used to monitor prostate cancer progression and response to therapy.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Liver metastases", "glycan_involvement": "Glycosylation modulates GGT activity and serum levels.", "mechanism": "Elevated GGT is associated with liver metastases and increased risk of severe DILI.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Liver metastases", "glycan_involvement": "Glycosylation affects ALP secretion and activity.", "mechanism": "ALP elevation may indicate liver metastases in prostate cancer patients.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Minor glycosylation may affect serum half-life.", "mechanism": "Elevated LDH may reflect hepatocellular damage in DILI.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135411" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycation of hemoglobin is a direct measure of glucose exposure.", "mechanism": "Reflects chronic hyperglycemia and insulin resistance, which are linked to hypertension risk.", "protein": "Glycosylated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Albumin glycosylation status may affect vascular function.", "mechanism": "Lower albumin levels associated with increased hypertension risk, possibly via endothelial dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "LDL glycosylation can modulate its atherogenicity.", "mechanism": "Elevated LDL-C is associated with hypertension and cardiovascular risk.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "HDL glycosylation may affect its anti-inflammatory properties.", "mechanism": "Lower HDL-C levels are associated with increased hypertension risk.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "LDH glycosylation may influence its stability and activity.", "mechanism": "Elevated LDH may reflect tissue damage or metabolic stress in hypertension.", "protein": "Lactate Dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation of platelet surface proteins affects aggregation.", "mechanism": "Platelet count and function are altered in hypertension.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates immune cell interactions.", "mechanism": "WBC count is associated with inflammation in hypertension.", "protein": "White Blood Cell Surface Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "ALT glycosylation may affect enzyme activity.", "mechanism": "Elevated ALT may indicate metabolic dysfunction linked to hypertension.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "AST glycosylation may influence function.", "mechanism": "Elevated AST may reflect metabolic stress in hypertension.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Reflects glycoprotein metabolism via glucose and lipid pathways.", "mechanism": "TyG index is a surrogate marker for insulin resistance, which causally contributes to hypertension.", "protein": "Triglyceride-Glucose Index (TyG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135444" }, { "confidence": "high", "disease": "Intrauterine growth restriction (IUGR)", "glycan_involvement": "Glycosylation is essential for PAPP-A secretion and stability in maternal serum.", "mechanism": "Low PAPP-A impairs IGF activation, reducing trophoblastic invasion and placental vascularization, leading to fetal growth restriction.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "high", "disease": "Placental insufficiency", "glycan_involvement": "Glycosylation affects PAPP-A's enzymatic activity and interaction with IGF-binding proteins.", "mechanism": "Low PAPP-A reflects early placental dysfunction due to impaired IGF signaling and spiral artery remodeling.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "medium", "disease": "Small-for-gestational-age (SGA)", "glycan_involvement": "Glycosylation required for PAPP-A's bioactivity in maternal circulation.", "mechanism": "Low PAPP-A levels are associated with reduced fetal growth and SGA outcomes.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation modulates PAPP-A's stability and function.", "mechanism": "Low PAPP-A is linked to impaired placental development and increased risk of hypertensive disorders.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "medium", "disease": "Confined placental mosaicism (CPM)", "glycan_involvement": "Glycosylation status may affect detection and quantification in serum.", "mechanism": "Low PAPP-A may indicate underlying placental genomic abnormalities such as CPM.", "protein": "Pregnancy-associated plasma protein-A (PAPP-A)", "protein_enriched": { "function": "Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is", "gene_name": "PAPPA", "glycan_count": 11, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G70696MD", "G46503DX", "G84862VB", "G62765YT", "G02815KT", "G06110VR", "G23719VF", "G31852PQ", "G41247ZX", "G80920RR", "G90659AW" ], "uniprot_id": "Q13219" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "medium", "disease": "Intrauterine growth restriction (IUGR)", "glycan_involvement": "Glycosylation is critical for \u03b2-hCG's secretion, stability, and receptor binding.", "mechanism": "Low \u03b2-hCG suggests trophoblastic insufficiency and impaired placental development, increasing IUGR risk.", "protein": "Beta-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "medium", "disease": "Placental insufficiency", "glycan_involvement": "Glycosylation modulates \u03b2-hCG's biological activity and half-life.", "mechanism": "Low \u03b2-hCG reflects poor trophoblastic invasion and placental dysfunction.", "protein": "Beta-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "low", "disease": "Small-for-gestational-age (SGA)", "glycan_involvement": "Glycosylation required for \u03b2-hCG's function in maternal-fetal signaling.", "mechanism": "Low \u03b2-hCG levels are associated with reduced fetal growth and SGA outcomes.", "protein": "Beta-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "low", "disease": "Confined placental mosaicism (CPM)", "glycan_involvement": "Glycosylation status may affect immunoassay detection.", "mechanism": "Low \u03b2-hCG may indicate placental genomic abnormalities such as CPM.", "protein": "Beta-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation influences \u03b2-hCG's stability and activity.", "mechanism": "Low \u03b2-hCG may be associated with increased risk of hypertensive disorders due to placental dysfunction.", "protein": "Beta-human chorionic gonadotropin (\u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135480" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CD2AP interacts with glycoproteins (APP, Reelin, ApoER2) affecting their trafficking and signaling.", "mechanism": "CD2AP polymorphisms increase AD risk; loss of function affects APP processing, tau phosphorylation, synaptic and vascular function.", "protein": "CD2AP", "relationship_type": "causal/genetic risk factor", "source_pmcid": "PMC12135550" }, { "confidence": "high", "disease": "Focal segmental glomerulosclerosis (FSGS)", "glycan_involvement": "CD2AP interacts with podocin (glycoprotein) in lipid rafts, affecting junction stability.", "mechanism": "Mutations in CD2AP disrupt podocyte slit diaphragm, leading to proteinuria and nephropathy.", "protein": "CD2AP", "relationship_type": "causal/genetic risk factor", "source_pmcid": "PMC12135550" }, { "confidence": "high", "disease": "Cognitive impairment", "glycan_involvement": "CD2AP regulates glycoprotein-mediated signaling (Reelin/ApoER2) in brain endothelium.", "mechanism": "Low vascular CD2AP correlates with poor episodic and semantic memory; endothelial CD2AP knockout mice show memory deficits.", "protein": "CD2AP", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12135550" }, { "confidence": "medium", "disease": "Tauopathies (AD, Pick's disease)", "glycan_involvement": "Indirect; CD2AP may affect glycoprotein trafficking relevant to tau propagation.", "mechanism": "CD2AP neuronal inclusions co-localize with hyperphosphorylated tau; CD2AP loss increases tau pathology via p38 kinase.", "protein": "CD2AP", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135550" }, { "confidence": "medium", "disease": "Cerebral amyloid angiopathy (CAA)", "glycan_involvement": "CD2AP regulates ApoER2 (glycoprotein) signaling in endothelium.", "mechanism": "Loss of endothelial CD2AP does not trigger CAA but alters vessel reactivity to A\u03b2.", "protein": "CD2AP", "relationship_type": "protective/causal", "source_pmcid": "PMC12135550" }, { "confidence": "medium", "disease": "Cerebral small vessel disease", "glycan_involvement": "CD2AP modulates glycoprotein-mediated cell adhesion and junctions.", "mechanism": "Lower CD2AP expression associated with small vessel disease and vascular dysfunction.", "protein": "CD2AP", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12135550" }, { "confidence": "low", "disease": "Fibromuscular dysplasia", "glycan_involvement": "Indirect; CD2AP affects cell\u2013cell junctions involving glycoproteins.", "mechanism": "CD2AP polymorphism rs9296551 linked to arterial narrowing and fibrous tissue accumulation.", "protein": "CD2AP", "relationship_type": "genetic risk factor", "source_pmcid": "PMC12135550" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP glycosylation and lactylation modulate CD2AP interaction and degradation pathway.", "mechanism": "APP misprocessing leads to A\u03b2 accumulation; CD2AP promotes APP degradation and prevents A\u03b2 buildup.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12135550" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Reelin is a glycoprotein; its signaling depends on glycosylation for receptor interaction.", "mechanism": "Reelin/ApoER2 signaling counteracts vasoconstriction and restores cerebral blood flow in CD2AP-deficient mice.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "therapeutic target/protective", "source_pmcid": "PMC12135550" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "ApoER2 glycosylation is critical for ligand binding and signaling.", "mechanism": "ApoER2 signaling via Reelin and CD2AP regulates vasodilation and cognitive function.", "protein": "ApoER2", "relationship_type": "therapeutic target", "source_pmcid": "PMC12135550" }, { "confidence": "high", "disease": "Pelvic abscess", "glycan_involvement": "Mucin-type O-glycosylation is essential for CA125's stability and detection.", "mechanism": "Elevated serum CA125 correlates with abscess severity and extent of peritoneal involvement.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "high", "disease": "Peritoneal inflammation", "glycan_involvement": "O-glycosylation modulates immunoreactivity and serum levels.", "mechanism": "CA125 increases in response to peritoneal inflammation, reflecting disease severity.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Pelvic inflammatory disease (PID)", "glycan_involvement": "Glycosylation affects antigenicity and diagnostic utility.", "mechanism": "CA125 is elevated in PID-associated pelvic abscesses, indicating inflammatory activity.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "high", "disease": "Pelvic abscess", "glycan_involvement": "N-glycosylation required for CRP secretion and function.", "mechanism": "CRP is elevated in acute pelvic abscess, indicating systemic inflammation.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Pelvic abscess", "glycan_involvement": "Glycosylation influences stability and serum half-life.", "mechanism": "PCT is increased in bacterial pelvic abscess, useful for early infection diagnosis.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Pelvic abscess", "glycan_involvement": "Glycosylation affects CA125's detectability and clinical utility.", "mechanism": "CA125-guided decision-making may optimize timing of surgical intervention.", "protein": "CA125 (MUC16)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135603" }, { "confidence": "high", "disease": "Pelvic abscess", "glycan_involvement": "O-glycosylation critical for CA125's serum stability.", "mechanism": "Higher CA125 predicts longer antibiotic use, pain relief time, and hospital stay.", "protein": "CA125 (MUC16)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Pelvic abscess", "glycan_involvement": "N-glycosylation required for CRP's function.", "mechanism": "CRP levels reflect acute phase but less sensitive in advanced abscess.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Pelvic abscess", "glycan_involvement": "Glycosylation modulates serum levels.", "mechanism": "PCT is highest in acute phase, indicating infection stage.", "protein": "Procalcitonin (PCT)", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "high", "disease": "Pelvic abscess", "glycan_involvement": "O-glycosylation influences antigenic properties.", "mechanism": "CA125 elevation helps stratify patients for early invasive intervention.", "protein": "CA125 (MUC16)", "relationship_type": "risk stratification biomarker", "source_pmcid": "PMC12135603" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "N-glycosylation affects stability and clearance", "mechanism": "Serum Cystatin C used in Cr/CysC*100 index to estimate muscle mass", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "medium", "disease": "Chronic heart failure (CHF)", "glycan_involvement": "N-glycosylation may influence serum levels", "mechanism": "Cr/CysC*100 index proposed for risk stratification in CHF", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "high", "disease": "Chronic heart failure (CHF)", "glycan_involvement": "Platelet surface glycoproteins mediate activation and aggregation", "mechanism": "PLR (platelet-lymphocyte ratio) predicts mortality risk in CHF", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "high", "disease": "Death (all-cause mortality)", "glycan_involvement": "Glycosylation modulates platelet function and inflammation", "mechanism": "Elevated PLR associated with increased risk of death within 30 days and overall", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation affects neutrophil adhesion and migration", "mechanism": "NLR (neutrophil-lymphocyte ratio) proposed for sarcopenia screening", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "low", "disease": "Death (all-cause mortality)", "glycan_involvement": "Glycosylation modulates immune response", "mechanism": "NLR associated with mortality in univariate analysis, not after adjustment", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycosylation regulates lymphocyte trafficking", "mechanism": "PLR reflects immune status, correlates with frailty", "protein": "Lymphocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Minor glycosylation, limited impact", "mechanism": "AST/ALT ratio proposed as sarcopenia indicator", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "low", "disease": "Death (all-cause mortality)", "glycan_involvement": "Minor glycosylation, limited impact", "mechanism": "AST/ALT ratio associated with mortality in univariate analysis only", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycosylation modulates platelet-immune interactions", "mechanism": "PLR positively correlated with frailty, which increases mortality risk", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12135606" }, { "confidence": "high", "disease": "Non-resolution mural thrombus in left ventricular aneurysm (MTLVA)", "glycan_involvement": "Lp(a) contains heavily glycosylated apolipoprotein(a), which modulates its function and clearance.", "mechanism": "Elevated Lp(a) (>270 mg/L) independently predicts persistent or recurrent mural thrombus, likely due to its pro-thrombotic and anti-fibrinolytic properties.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation of apo(a) affects Lp(a) stability and thrombogenicity.", "mechanism": "High Lp(a) levels are associated with increased risk of stroke in patients with non-resolving mural thrombus.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Systemic embolism", "glycan_involvement": "Glycosylation influences Lp(a) interaction with vascular components.", "mechanism": "Elevated Lp(a) increases risk of systemic embolism via persistent thrombus formation.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Non-resolution mural thrombus in left ventricular aneurysm (MTLVA)", "glycan_involvement": "D-Dimer is a glycosylated fragment of cross-linked fibrin.", "mechanism": "Elevated D-Dimer (>780 ng/mL) is associated with non-resolution, reflecting ongoing coagulation and fibrinolysis.", "protein": "D-Dimer", "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Major adverse cardiovascular events (MACE)", "glycan_involvement": "NT-proBNP is glycosylated, affecting its stability and plasma half-life.", "mechanism": "High NT-proBNP is independently associated with adverse events in patients with mural thrombus.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Non-resolution mural thrombus in left ventricular aneurysm (MTLVA)", "glycan_involvement": "LDL and HDL particles contain glycoproteins (apoB, apoA-I) whose glycosylation modulates lipid metabolism and vascular inflammation.", "mechanism": "Hypercholesterolemia is an independent risk factor for thrombus non-resolution.", "protein": "Total Cholesterol (LDL/HDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "ST-segment elevation myocardial infarction (STEMI)", "glycan_involvement": "Glycosylation of apo(a) affects Lp(a) atherogenicity.", "mechanism": "Lp(a) is a causal risk factor for atherosclerotic cardiovascular disease, contributing to STEMI pathogenesis.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Major adverse cardiovascular events (MACE)", "glycan_involvement": "Glycosylation modulates Lp(a) function in thrombosis and inflammation.", "mechanism": "High Lp(a) predicts increased risk of MACE in patients with mural thrombus.", "protein": "Lipoprotein(a)", "protein_enriched": { "function": "Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for mega", "gene_name": "LPA", "glycan_count": 21, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G27391WQ", "G29068FM", "G43417UB", "G11629QQ", "G13694XX", "G37881RL", "G06356OH", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G82830MN", "G84452RH", "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G77252PU", "G81006GJ", "G93284HQ" ], "uniprot_id": "P08519" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "medium", "disease": "Non-resolution mural thrombus in left ventricular aneurysm (MTLVA)", "glycan_involvement": "Glycosylation affects NT-proBNP secretion and stability.", "mechanism": "Elevated NT-proBNP is associated with poor outcomes and non-resolution of mural thrombus.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "low", "disease": "Major adverse cardiovascular events (MACE)", "glycan_involvement": "D-Dimer glycosylation influences its clearance and detection.", "mechanism": "High D-Dimer reflects ongoing thrombosis and predicts adverse events.", "protein": "D-Dimer", "relationship_type": "biomarker", "source_pmcid": "PMC12135672" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "B-chain binds cell surface glycans for cell entry", "mechanism": "Cytotoxicity via ribosome inactivation in cancer cells", "protein": "Modeccin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "B-chain lectin domain binds glycan structures on target cells", "mechanism": "Selective toxicity against cancer cell lines by inhibiting protein synthesis", "protein": "Volkensin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "B-chain binds to cell surface glycans for internalization", "mechanism": "Depurinates 28S rRNA, halting protein synthesis in tumor cells", "protein": "Stenodactylin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "Antibiotic-resistant bacterial infections", "glycan_involvement": "Lectin domain recognizes bacterial surface glycans", "mechanism": "Disrupts microbial membranes and protein synthesis", "protein": "Galactose-binding lectin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "HIV/AIDS opportunistic infections", "glycan_involvement": "B-chain binds glycosylated receptors on immune cells", "mechanism": "Immune modulation and cytotoxicity against infected cells", "protein": "Modeccin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation enhances solubility and bioactivity", "mechanism": "Antioxidant activity reduces oxidative stress and improves insulin sensitivity", "protein": "Rutin", "relationship_type": "protective", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation increases stability and absorption", "mechanism": "Promotes iron bioavailability and red blood cell production", "protein": "Vitexin", "relationship_type": "protective", "source_pmcid": "PMC12135688" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "B-chain binds hepatocyte surface glycans", "mechanism": "Hepatotoxicity due to ribosome inactivation in liver cells", "protein": "Modeccin", "relationship_type": "causal", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "B-chain lectin domain may bind parasite surface glycans", "mechanism": "Antiplasmodial activity via inhibition of parasite protein synthesis", "protein": "Modeccin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135688" }, { "confidence": "medium", "disease": "Rheumatism", "glycan_involvement": "Glycosylation enhances anti-inflammatory properties", "mechanism": "Anti-inflammatory activity reduces joint inflammation", "protein": "\u03b2-sitosterol-3-O-\u03b2-D-glucopyranoside", "relationship_type": "protective", "source_pmcid": "PMC12135688" }, { "confidence": "high", "disease": "Antidepressant-induced adverse events", "glycan_involvement": "N-glycosylation modulates ABCB1 trafficking and function.", "mechanism": "ABCB1 variants (e.g., rs2032582, rs1045642) affect drug efflux at the blood-brain barrier, influencing antidepressant bioavailability and side effect risk.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "medium", "disease": "Antidepressant non-response", "glycan_involvement": "N-glycosylation affects substrate specificity and transporter stability.", "mechanism": "ABCB1 rs1045642 (C3435T) associated with remission rates and required dose for escitalopram/venlafaxine.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "high", "disease": "Akathisia (venlafaxine-induced)", "glycan_involvement": "N-glycosylation may alter transporter function at the BBB.", "mechanism": "ABCB1 rs2032582 minor T allele increases risk of venlafaxine-induced akathisia.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "medium", "disease": "Suicidal ideation (drug-induced)", "glycan_involvement": "N-glycosylation impacts protein stability and drug transport.", "mechanism": "ABCB1 rs2032582 minor T allele linked to increased suicidal ideation during antidepressant therapy.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "high", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "N-glycosylation regulates transporter localization and activity.", "mechanism": "SLC6A4 variants modulate SSRI response by altering serotonin reuptake.", "protein": "SLC6A4 (Serotonin transporter)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135885" }, { "confidence": "medium", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "N-glycosylation affects receptor folding and signaling.", "mechanism": "HTR2A variants influence SSRI efficacy and side effect profile.", "protein": "HTR2A (Serotonin receptor 2A)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "medium", "disease": "Antidepressant non-response", "glycan_involvement": "N-glycosylation modulates BDNF secretion and stability.", "mechanism": "BDNF rs6265 (Val66Met) variant associated with differential antidepressant response/remission, especially in Asian and elderly populations.", "protein": "BDNF (Brain-derived neurotrophic factor)", "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "low", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Potential N-glycosylation may affect enzyme activity.", "mechanism": "COMT rs4680 (Val158Met) variant affects catecholamine metabolism, influencing antidepressant response.", "protein": "COMT (Catechol-O-methyltransferase)", "protein_enriched": { "function": "Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, ", "gene_name": "COMT", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21964" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "medium", "disease": "Antidepressant non-response", "glycan_involvement": "Glycosylation may affect G protein signaling.", "mechanism": "GNB3 rs5443 (C825T) variant consistently associated with antidepressant efficacy.", "protein": "GNB3 (G protein subunit beta-3)", "protein_enriched": { "function": "Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, f", "gene_name": "GNG12", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBI6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "low", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "HTR1A rs6295 variant influences antidepressant response.", "protein": "HTR1A (Serotonin receptor 1A)", "protein_enriched": { "function": "G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a", "gene_name": "HTR1A", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08908" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135885" }, { "confidence": "high", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "N-linked glycosylation affects protein folding, stability, and antiviral function.", "mechanism": "Inhibits release of CIV from infected cells by physically retaining viral particles at the cell surface.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Influenza A Virus (IAV) infection", "glycan_involvement": "N-linked glycosylation is conserved and important for function.", "mechanism": "Restricts release of IAV particles from host cells; activity is strain-specific.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Human Immunodeficiency Virus type 1 (HIV-1) infection", "glycan_involvement": "N-linked glycosylation modulates antiviral activity.", "mechanism": "Prevents release of HIV-1 virions from infected cells.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Vesicular Stomatitis Virus (VSV) infection", "glycan_involvement": "N-linked glycosylation involved in protein function.", "mechanism": "Restricts VSV release from host cells.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Dengue Virus (DENV) infection", "glycan_involvement": "N-linked glycosylation affects antiviral activity.", "mechanism": "Inhibits DENV release from infected cells.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "high", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "Glycosylation pattern may be altered by domain deletions, affecting function.", "mechanism": "TM domain is critical for antiviral activity; deletion abolishes CIV restriction.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "Glycosylation status can be detected by Western blot.", "mechanism": "Expression induced by interferon during CIV infection; marker of antiviral response.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "CC domain contains glycosylation sites; deletion affects glycosylation and expression.", "mechanism": "Deletion of CC or CT domains reduces but does not abolish antiviral activity.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "GPI anchor not required for canine tetherin antiviral function.", "mechanism": "Deletion of GPI domain does not affect antiviral activity against CIV (unlike human tetherin).", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12135924" }, { "confidence": "medium", "disease": "Canine Influenza Virus (CIV) infection", "glycan_involvement": "Direct involvement of N-linked glycosylation in antiviral function.", "mechanism": "N-linked glycosylation at N72 and N99 is conserved and may be important for antiviral activity.", "protein": "Tetherin (BST-2/CD317/HM1.24)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12135924" }, { "confidence": "high", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "VTN is a glycoprotein; glycosylation may affect its adhesive and regulatory functions.", "mechanism": "Downregulated phosphorylation and expression; involved in cell adhesion, coagulation, and tissue remodeling.", "protein": "Vitronectin (VTN)", "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "high", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "PLG is a glycoprotein; glycosylation influences activation and function.", "mechanism": "Downregulated phosphorylation and expression; promotes wound healing and inflammatory cell recruitment.", "protein": "Plasminogen (PLG)", "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "high", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "C3 is a glycoprotein; glycosylation modulates complement activity.", "mechanism": "Elevated phosphorylation increases sensitivity to proteolytic cleavage, enhancing complement activation and immune response.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Bleeding in HZ", "glycan_involvement": "ADAMTSL4 is a glycoprotein; glycosylation may affect secretion and function.", "mechanism": "Increased phosphorylation; involved in angiogenesis, possibly linked to bleeding complications.", "protein": "ADAMTSL4", "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Bleeding in HZ", "glycan_involvement": "SERPINA10 is a glycoprotein; glycosylation affects inhibitory activity.", "mechanism": "Increased phosphorylation; regulates coagulation, associated with bleeding risk.", "protein": "SERPINA10", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:21350122). IL17A-IL17F signals via IL17RA-IL17RC heterodimeric", "gene_name": "IL17F", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G26551VB" ], "uniprot_id": "Q96PD4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "HSP90AA1 is a glycoprotein; glycosylation may influence chaperone activity.", "mechanism": "Upregulated phosphorylation; facilitates viral protein assembly and replication.", "protein": "HSP90AA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "HSP90AB1 is a glycoprotein; glycosylation may modulate immune signaling.", "mechanism": "Upregulated phosphorylation; involved in IL-17 signaling and viral replication.", "protein": "HSP90AB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "HSP90B1 is a glycoprotein; glycosylation affects ER localization and function.", "mechanism": "Upregulated phosphorylation; participates in ER protein processing and IL-17 pathway.", "protein": "HSP90B1", "protein_enriched": { "function": "Involved in synthesis of starch. Catalyzes the synthesis of ADP-glucose, a molecule that serves as an activated glycosyl donor for alpha-1,4-glucan synthesis. Essential for starch synthesis in leaf ch", "gene_name": "AGPL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q688T8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "FGA is a glycoprotein; glycosylation critical for clot formation.", "mechanism": "Phosphorylation site upregulated; involved in coagulation cascades.", "protein": "Fibrinogen alpha chain (FGA)", "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "medium", "disease": "Herpes Zoster (HZ)", "glycan_involvement": "IGFBP1 is a glycoprotein; glycosylation regulates IGF binding.", "mechanism": "Phosphorylation site upregulated; modulates IGF signaling and may affect immune response.", "protein": "IGFBP1", "relationship_type": "biomarker", "source_pmcid": "PMC12135958" }, { "confidence": "high", "disease": "Systemic sclerosis", "glycan_involvement": "DPP4 is a glycoprotein; glycosylation may affect its stability and cell surface expression.", "mechanism": "DPP4 is highly expressed in activated fibroblasts in systemic sclerosis skin.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC12136023" }, { "confidence": "high", "disease": "Fibrosis (pulmonary)", "glycan_involvement": "Glycosylation may regulate DPP4 enzymatic activity and interactions.", "mechanism": "DPP4 inhibitors ameliorate bleomycin-induced pulmonary fibrosis in mice.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136023" }, { "confidence": "medium", "disease": "Cancer (breast, pancreatic, gastric, lung)", "glycan_involvement": "Glycosylation may modulate DPP4's role in tumor microenvironment.", "mechanism": "DPP4 is expressed in subsets of cancer-associated fibroblasts.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC12136023" }, { "confidence": "high", "disease": "Immunodeficiency", "glycan_involvement": "HS glycosaminoglycan chains are essential for chemokine immobilization.", "mechanism": "HS proteoglycans on fibroblasts guide thymocyte migration; loss impairs T cell development.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "O-glycosylation of PDPN is critical for ligand binding.", "mechanism": "PDPN binds CCL21, aiding thymocyte migration; deficiency may impair T cell selection.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "high", "disease": "Autoimmune disease (general)", "glycan_involvement": "MMP9 is glycosylated; glycosylation may affect secretion and antigenicity.", "mechanism": "Loss of mFb-derived MMP9 (a TRA) leads to autoantibody production and autoimmunity.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "medium", "disease": "Autoimmune disease (general)", "glycan_involvement": "Glycosylation may affect antigen presentation.", "mechanism": "Loss of mFb-derived HMGCS2 (a TRA) leads to autoantibody production and autoimmunity.", "protein": "HMGCS2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O92782" }, "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "medium", "disease": "Autoimmune polyendocrinopathy", "glycan_involvement": "CRP is glycosylated; glycosylation may affect antigenicity.", "mechanism": "CRP is a tissue-restricted antigen presented by mTECs; failure in presentation leads to autoimmunity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "high", "disease": "Immunodeficiency", "glycan_involvement": "N-glycosylation is essential for MHC I folding and surface expression.", "mechanism": "Defective antigen presentation by glycosylated MHC I on mFbs impairs negative selection.", "protein": "MHC class I (H2-K1, H2-D1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12136023" }, { "confidence": "medium", "disease": "Thymic involution", "glycan_involvement": "Glycosylation may regulate DPP4's cell surface localization.", "mechanism": "DPP4 marks capFbs, which increase in proportion during thymic involution.", "protein": "Dipeptidyl peptidase-4 (DPP4/CD26)", "relationship_type": "biomarker", "source_pmcid": "PMC12136023" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "TFEB itself is not glycosylated, but regulates lysosomal glycoproteins.", "mechanism": "TFEB degradation impairs lysosomal homeostasis; stabilizing TFEB protects against SARS-CoV-2 infection.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation; impacts glycoprotein turnover via TFEB pathway.", "mechanism": "DCAF7 mediates ubiquitin-dependent degradation of TFEB during coronavirus infection, reducing host defense.", "protein": "DCAF7", "relationship_type": "causal", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation; modulates TFEB stability.", "mechanism": "PAK2 phosphorylates TFEB, priming it for DCAF7-mediated degradation during viral infection.", "protein": "PAK2", "protein_enriched": { "function": "Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (Pub", "gene_name": "PAK2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q13177" }, "relationship_type": "causal", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation affects viral binding.", "mechanism": "ACE2 is hijacked by SARS-CoV-2 for cell entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune evasion.", "mechanism": "Spike protein mediates viral entry via ACE2.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12136031" }, { "confidence": "medium", "disease": "Lysosomal storage disorders", "glycan_involvement": "Regulates lysosomal glycoproteins.", "mechanism": "TFEB activation improves lysosomal function; potential therapy for lysosomal diseases.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Indirect via lysosomal glycoprotein regulation.", "mechanism": "TFEB stabilization reduces lung injury in SARS-CoV-2 animal models.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "protective", "source_pmcid": "PMC12136031" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NSP13 is not glycosylated; effect is via lysosomal pathway.", "mechanism": "TFEB activation promotes lysosomal degradation of NSP13, impairing viral replication.", "protein": "SARS-CoV-2 NSP13", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136031" }, { "confidence": "medium", "disease": "Hepatitis (MHV)", "glycan_involvement": "Regulates lysosomal glycoproteins.", "mechanism": "TFEB activation upregulates immune pathways and lysosomal exocytosis in MHV infection.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "protective", "source_pmcid": "PMC12136031" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NP is not glycosylated; effect is via lysosomal pathway.", "mechanism": "TFEB activation promotes lysosomal degradation of NP, reducing viral load.", "protein": "SARS-CoV-2 Nucleoprotein (NP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136031" }, { "confidence": "high", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "ICS are glycoprotein-based drugs; glycosylation affects stability and delivery.", "mechanism": "Reduces airway inflammation and exacerbations in COPD.", "protein": "Inhaled corticosteroids (ICS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136080" }, { "confidence": "high", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "LABA inhalers may contain glycoprotein excipients for delivery.", "mechanism": "Bronchodilation improves airflow and reduces exacerbations.", "protein": "Long-acting beta-agonist (LABA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136080" }, { "confidence": "high", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "LAMA formulations may use glycoprotein carriers.", "mechanism": "Blocks muscarinic receptors, reducing bronchoconstriction.", "protein": "Long-acting muscarinic antagonist (LAMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "O-glycosylation regulates mucus viscosity and clearance.", "mechanism": "Elevated in COPD, contributes to mucus hypersecretion and airway obstruction.", "protein": "Mucin-5AC (MUC5AC)", "relationship_type": "biomarker", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "O-glycosylation modulates mucin function.", "mechanism": "Altered expression in COPD, affects mucus properties.", "protein": "Mucin-5B (MUC5B)", "relationship_type": "biomarker", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "N-glycosylation required for SP-D oligomerization and function.", "mechanism": "SP-D levels reflect lung inflammation and injury.", "protein": "Surfactant protein D (SP-D)", "relationship_type": "biomarker", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Fc N-glycosylation modulates effector functions.", "mechanism": "IgG mediates immune defense against respiratory pathogens.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "N-glycosylation affects secretion and inhibitory activity.", "mechanism": "Deficiency leads to unchecked neutrophil elastase activity and lung damage.", "protein": "Alpha-1 antitrypsin (SERPINA1)", "relationship_type": "causal", "source_pmcid": "PMC12136080" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "N-glycosylation required for CRP stability and function.", "mechanism": "Elevated CRP indicates systemic inflammation and predicts exacerbations.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136080" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "N-glycosylation modulates cell adhesion properties.", "mechanism": "ICAM-1 upregulation promotes leukocyte recruitment in airway inflammation.", "protein": "Intercellular adhesion molecule 1 (ICAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12136080" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation affects cystatin C stability and serum levels.", "mechanism": "Elevated serum cystatin C is associated with increased osteoporosis risk, reflecting impaired renal function and altered bone metabolism.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation modulates albumin half-life and function.", "mechanism": "Low serum albumin correlates with osteoporosis, indicating poor nutritional status and systemic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Minor glycosylation may affect hemoglobin turnover.", "mechanism": "Reduced hemoglobin levels are predictive of osteoporosis, possibly due to chronic inflammation and impaired erythropoiesis.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "N-glycosylation influences serum cystatin C measurement.", "mechanism": "Cystatin C is a sensitive marker of glomerular filtration rate; elevated levels indicate renal dysfunction, which is linked to secondary osteoporosis.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects albumin's circulatory stability.", "mechanism": "Low albumin is associated with anemia and poor bone health.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation of apolipoproteins modulates LDL function.", "mechanism": "Altered LDL levels are observed in osteoporosis, reflecting changes in lipid metabolism and bone turnover.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects ApoAI stability and interaction with HDL.", "mechanism": "Lower ApoAI levels are linked to osteoporosis, possibly due to impaired lipid transport and bone cell function.", "protein": "Apolipoprotein AI", "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates RBP secretion and function.", "mechanism": "Altered RBP levels may reflect vitamin A status, impacting bone remodeling.", "protein": "Retinol-Binding Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Acute phase glycoproteins (e.g., fibrinogen) drive ESR elevation.", "mechanism": "Elevated ESR indicates inflammation, which contributes to bone loss in osteoporosis.", "protein": "Erythrocyte Sedimentation Rate (ESR) protein markers", "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "medium", "disease": "Tuberculosis Spondylitis", "glycan_involvement": "N-glycosylation affects cystatin C's immunological properties.", "mechanism": "Elevated cystatin C may reflect systemic inflammation and renal involvement in TS patients.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12136082" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "KIM-1 is a mucin-domain glycoprotein; glycosylation may affect shedding and detection in biofluids.", "mechanism": "KIM-1 is upregulated in proximal tubular cells in response to injury; elevated serum and urinary levels correlate negatively with eGFR and CKD stage.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "Glycosylation may influence KIM-1 stability and detection.", "mechanism": "KIM-1 is highly upregulated in response to ischemic and toxic insults; urinary KIM-1 is sensitive for early tubular injury.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "No direct evidence in article, but glycosylation may affect biomarker performance.", "mechanism": "Elevated plasma KIM-1 predicts eGFR decline in advanced diabetic kidney disease, independent of other risk factors.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "Lupus Nephritis", "glycan_involvement": "Not specified.", "mechanism": "Urinary KIM-1 levels correlate with renal function and improve diagnostic accuracy post-biopsy.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "Lead-induced Nephrotoxicity", "glycan_involvement": "Not specified.", "mechanism": "Urinary KIM-1 detects renal tubular injury in lead-exposed workers.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "COVID-19-related Kidney Dysfunction", "glycan_involvement": "Not specified.", "mechanism": "Normalized urinary KIM-1 is associated with kidney dysfunction in COVID-19 patients.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "End-stage Kidney Disease", "glycan_involvement": "Not specified.", "mechanism": "Urinary KIM-1 predicts progression to end-stage kidney disease in patients with type 1 diabetes and macroalbuminuria.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "medium", "disease": "Tubulointerstitial Inflammation", "glycan_involvement": "Not specified.", "mechanism": "Urinary KIM-1 levels are linked to tubulointerstitial inflammation.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "low", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Genetic variation may affect glycosylation patterns, but not demonstrated in this study.", "mechanism": "HAVCR1 SNP rs6555820 shows no direct association with KIM-1 levels or eGFR, but may have gender-dependent effects.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "genetic association", "source_pmcid": "PMC12136559" }, { "confidence": "low", "disease": "Mortality in Hemodialysis Patients", "glycan_involvement": "Not specified.", "mechanism": "Lower KIM-1 levels are linked to higher mortality risk, suggesting a complex role in prognosis.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12136559" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "GLP-1R agonists (e.g., liraglutide) promote weight loss via appetite suppression and improved metabolism.", "protein": "Glucagon-like peptide-1 receptor (GLP-1R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137074" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates receptor sensitivity and signaling.", "mechanism": "GLP-1R activation enhances insulin secretion and glycemic control.", "protein": "Glucagon-like peptide-1 receptor (GLP-1R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation influences peptide stability and receptor interaction.", "mechanism": "PYY secretion post-surgery reduces appetite and supports weight loss.", "protein": "Peptide YY (PYY)", "relationship_type": "causal/protective", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects peptide bioactivity.", "mechanism": "GIP receptor agonism (dual incretin therapy) may overcome GLP-1R desensitization.", "protein": "Gastric inhibitory polypeptide (GIP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates peptide secretion and activity.", "mechanism": "Reduced ghrelin post-sleeve gastrectomy decreases hunger.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "causal", "source_pmcid": "PMC12137074" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation essential for insulin folding and receptor binding.", "mechanism": "Insulin levels and HOMA-IR reflect metabolic improvement post-liraglutide.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycoprotein components affect LDL receptor interaction.", "mechanism": "LDL reduction indicates improved lipid metabolism after treatment.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "Glycosylation affects enzyme stability and secretion.", "mechanism": "ALT decrease reflects hepatic improvement post-liraglutide.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "Glycosylation impacts enzyme activity.", "mechanism": "AST decrease signals reduced liver injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137074" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "GGT reduction indicates improved liver function.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137074" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "O-GlcNAcylation by OGT stabilizes NLRP3, enhancing inflammasome activity.", "mechanism": "BPA/BPF exposure activates NLRP3 inflammasome, driving IL-1\u03b2/IL-18 release and hepatic inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Direct O-GlcNAc modification of NLRP3.", "mechanism": "BPA upregulates OGT, increasing O-GlcNAcylation of NLRP3, promoting hepatic pyroptosis and steatosis.", "protein": "OGT (O-GlcNAc transferase)", "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation status may affect APOD stability and function.", "mechanism": "APOD downregulation by BPA promotes triglyceride accumulation; APOD overexpression reverses steatosis.", "protein": "APOD (Apolipoprotein D)", "relationship_type": "protective", "source_pmcid": "PMC12137076" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may modulate SCD1 activity.", "mechanism": "BPA/BPS exposure upregulates SCD1, enhancing fatty acid biosynthesis and lipid accumulation.", "protein": "SCD1", "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "N-glycosylation required for CD36 membrane localization and function.", "mechanism": "BPA and high-fat diet upregulate CD36, increasing hepatic fatty acid uptake and steatosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect IRS-1 stability and signaling.", "mechanism": "BPA impairs IRS-1/PI3K/Akt signaling, leading to hepatic insulin resistance.", "protein": "IRS-1", "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "N-glycosylation essential for TLR4 ligand recognition.", "mechanism": "BPA-induced gut dysbiosis increases endotoxin, activating hepatic TLR4/NF-\u03baB pathway and inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "medium", "disease": "Pyroptosis", "glycan_involvement": "Glycosylation may regulate CASP1 activation.", "mechanism": "BPF/BPA exposure activates NLRP3/CASP1 axis, triggering pyroptotic cell death in liver.", "protein": "CASP1 (Caspase-1)", "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects IL-1\u03b2 secretion and stability.", "mechanism": "NLRP3 activation increases IL-1\u03b2 secretion, correlating with NAFLD severity.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137076" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may influence EP300 localization and activity.", "mechanism": "BPS activates EP300, leading to Raptor acetylation, mTORC1 activation, and impaired autophagy, promoting steatosis.", "protein": "EP300", "relationship_type": "causal", "source_pmcid": "PMC12137076" }, { "confidence": "high", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "PEGylation alters pharmacokinetics and tissue distribution.", "mechanism": "PLD accumulates in skin exocrine glands, causing toxicity and inflammation.", "protein": "Pegylated liposomal doxorubicin (PLD)", "relationship_type": "causal", "source_pmcid": "PMC12137081" }, { "confidence": "high", "disease": "Oral mucositis (OM)", "glycan_involvement": "PEGylation enhances mucosal retention.", "mechanism": "PLD accumulates in oral mucosa, leading to mucosal damage and ulceration.", "protein": "Pegylated liposomal doxorubicin (PLD)", "relationship_type": "causal", "source_pmcid": "PMC12137081" }, { "confidence": "medium", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation affects Hb stability and oxygen delivery.", "mechanism": "Low Hb exacerbates tissue hypoxia and ROS generation, increasing HFS risk.", "protein": "Hemoglobin (Hb)", "relationship_type": "biomarker", "source_pmcid": "PMC12137081" }, { "confidence": "high", "disease": "Oral mucositis (OM)", "glycan_involvement": "Cell surface glycoproteins mediate immune cell interactions.", "mechanism": "Low WBC count impairs immune defense and mucosal repair, increasing OM risk.", "protein": "White blood cell (WBC) glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12137081" }, { "confidence": "medium", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT indicates liver dysfunction, reducing PLD clearance and increasing HFS risk.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137081" }, { "confidence": "medium", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated AST reflects liver injury, contributing to PLD accumulation and HFS.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137081" }, { "confidence": "low", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "N-glycosylation modulates HER-2 signaling.", "mechanism": "HER-2+ status previously linked to increased HFS risk, but not confirmed in this study.", "protein": "HER-2 (ERBB2)", "relationship_type": "biomarker", "source_pmcid": "PMC12137081" }, { "confidence": "low", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation essential for EPO stability and function.", "mechanism": "EPO may support vascular repair and oxygen delivery, mitigating HFS.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "protective", "source_pmcid": "PMC12137081" }, { "confidence": "medium", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation affects cytokine secretion and activity.", "mechanism": "Liver injury increases TNF-\u03b1, promoting inflammation and microvascular damage in HFS.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137081" }, { "confidence": "medium", "disease": "Hand-foot syndrome (HFS)", "glycan_involvement": "Glycosylation modulates IL-6 receptor binding.", "mechanism": "IL-6 released during liver injury intensifies systemic inflammation and HFS.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12137081" }, { "confidence": "high", "disease": "Acute Ischemic Stroke", "glycan_involvement": "Insulin receptor glycosylation modulates insulin signaling and resistance.", "mechanism": "TyG index reflects insulin resistance, which increases risk of vascular events and poor stroke prognosis.", "protein": "TyG index (Triglyceride-Glucose index)", "relationship_type": "biomarker", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Mortality (all-cause, post-stroke)", "glycan_involvement": "Albumin glycosylation affects its stability and anti-inflammatory properties.", "mechanism": "Higher serum albumin is protective against one-year mortality after stroke.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Mortality (all-cause, post-stroke)", "glycan_involvement": "Glycosylation may affect AST secretion and activity.", "mechanism": "Elevated AST is an independent risk factor for one-year mortality post-stroke.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Stroke Recurrence", "glycan_involvement": "LDL glycoprotein components influence receptor binding and clearance.", "mechanism": "Higher LDL levels were protective against stroke recurrence in non-diabetic patients.", "protein": "LDL", "relationship_type": "protective", "source_pmcid": "PMC12137084" }, { "confidence": "high", "disease": "Stroke Recurrence", "glycan_involvement": "Glycosylation of enzymes in homocysteine metabolism affects their activity.", "mechanism": "Hyperhomocysteinemia increases risk of stroke recurrence and interacts with TyG index.", "protein": "Homocysteine-related glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12137084" }, { "confidence": "high", "disease": "Mortality (all-cause, post-stroke)", "glycan_involvement": "Reflects altered glycoprotein insulin receptor function.", "mechanism": "Higher TyG index independently predicts increased one-year mortality in non-diabetic stroke patients.", "protein": "TyG index (Triglyceride-Glucose index)", "relationship_type": "biomarker", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Stroke Recurrence", "glycan_involvement": "Age-dependent glycosylation changes may modulate risk.", "mechanism": "Higher TyG index is protective against recurrence in patients under 65 years.", "protein": "TyG index (Triglyceride-Glucose index)", "relationship_type": "protective", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Adverse Functional Outcomes (mRS >2)", "glycan_involvement": "Possible age-related glycosylation effects on vascular and metabolic proteins.", "mechanism": "Higher TyG index is protective against poor functional outcomes in patients under 65.", "protein": "TyG index (Triglyceride-Glucose index)", "relationship_type": "protective", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIIb/IIIa) require glycosylation for function.", "mechanism": "Insulin resistance enhances platelet glycoprotein-mediated adhesion and aggregation, increasing stroke risk.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12137084" }, { "confidence": "medium", "disease": "Mortality (all-cause, post-stroke)", "glycan_involvement": "Glycosylation modulates WBC adhesion and signaling.", "mechanism": "Elevated WBC count is an independent risk factor for mortality; glycoproteins mediate immune response.", "protein": "White blood cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12137084" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT reflects increased oxidative stress and glutathione turnover in MASLD.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is glycosylated, which may affect its serum levels.", "mechanism": "ALT elevation indicates hepatocyte injury and is a key marker in MASLD diagnosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST glycosylation may influence its release and activity.", "mechanism": "AST elevation, especially in ratio to ALT, reflects liver injury severity in MASLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation modulates GGT activity and serum detection.", "mechanism": "GGT increases with hepatic fat accumulation and oxidative stress.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may affect ALT stability and detection.", "mechanism": "ALT is elevated in hepatic steatosis due to hepatocyte damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect TM6SF2 function in lipid metabolism.", "mechanism": "Genetic variants in TM6SF2 increase hepatic lipid accumulation and MASLD risk.", "protein": "Transmembrane 6 superfamily member 2 (TM6SF2)", "relationship_type": "causal", "source_pmcid": "PMC12137091" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may modulate PNPLA3 activity.", "mechanism": "PNPLA3 variants promote hepatic fat accumulation and MASLD development.", "protein": "Patatin-like phospholipase domain-containing protein 3 (PNPLA3)", "protein_enriched": { "function": "Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity)", "gene_name": "Enpp5", "glycan_count": 6, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G14260UH", "G64527OM", "G74724QE", "G14669DU", "G70101JE", "G80920RR" ], "uniprot_id": "Q9EQG7" }, "relationship_type": "causal", "source_pmcid": "PMC12137091" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences GGT serum levels and activity.", "mechanism": "Elevated GGT is associated with increased risk and mortality in MASLD-related HCC.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation may affect ALT turnover and detection.", "mechanism": "ALT elevation correlates with progression to fibrosis in MASLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "medium", "disease": "Insulin resistance (IR)", "glycan_involvement": "Glycosylation modulates GGT function in oxidative stress response.", "mechanism": "GGT elevation reflects oxidative stress linked to IR in MASLD.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12137091" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation affects Apo Ai stability and HDL function.", "mechanism": "Lower Apo Ai levels are associated with higher CHD risk; Apo Ai is anti-atherosclerotic.", "protein": "Apolipoprotein A-I (Apo Ai)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Lp(a) is heavily glycosylated; glycan structure modulates its atherogenicity.", "mechanism": "Abnormal Lp(a) levels are associated with increased CHD risk in T2DM.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Non-enzymatic glycation (advanced glycation end-products) drives endothelial dysfunction.", "mechanism": "Elevated HbA1c reflects chronic hyperglycemia, promoting vascular damage and CHD.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12137098" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "N-glycosylation modulates fibrinogen function and clot formation.", "mechanism": "Elevated fibrinogen increases thrombosis risk and is linked to CHD in T2DM.", "protein": "Fibrinogen (FIB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12137098" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation status can affect albumin\u2019s antioxidant properties.", "mechanism": "Lower albumin levels may reflect inflammation and vascular risk in T2DM-CHD.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation of HDL components influences anti-atherogenic function.", "mechanism": "Lower HDL-C (Apo Ai-containing) is associated with higher CHD risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12137098" }, { "confidence": "medium", "disease": "Coronary Heart Disease (CHD)", "glycan_involvement": "Glycosylation may affect AST stability and activity.", "mechanism": "Elevated AST reflects myocardial cell damage and is predictive of CHD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of apolipoprotein(a) modulates its binding and pathogenicity.", "mechanism": "Lp(a) promotes atherogenesis via pro-inflammatory and pro-thrombotic effects.", "protein": "Lipoprotein(a) [Lp(a)]", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation enhances Apo Ai\u2019s anti-atherogenic activity.", "mechanism": "Apo Ai facilitates cholesterol efflux and inhibits plaque formation.", "protein": "Apolipoprotein A-I (Apo Ai)", "relationship_type": "protective", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Advanced glycation end-products (AGEs) drive vascular inflammation.", "mechanism": "Glycated hemoglobin promotes endothelial dysfunction and plaque development.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "causal", "source_pmcid": "PMC12137098" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "Mediates platelet aggregation; inhibitors reduce thrombotic and inflammatory responses.", "protein": "GPIIb/IIIa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation required for ligand recognition and aggregate formation.", "mechanism": "Promotes platelet-monocyte aggregate formation, correlates with poor outcomes.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates stability and receptor interaction.", "mechanism": "Elevated in plasma; reduced by aspirin, indicating platelet-driven inflammation.", "protein": "CD154 (CD40L)", "relationship_type": "biomarker", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation affects receptor activation and aggregation.", "mechanism": "Elevated platelet-monocyte aggregates via GPIIb/IIIa; inhibitors reduce aggregates.", "protein": "GPIIb/IIIa", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Stroke (cryptogenic, cardioembolic)", "glycan_involvement": "Glycosylation essential for selectin-mediated cell adhesion.", "mechanism": "Increased P-selectin expression and PMA/PNAs in stroke patients.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Cancer (metastasis)", "glycan_involvement": "Glycosylation of MHC-I affects immune recognition.", "mechanism": "Platelets transfer MHC-I to tumor cells, enabling immune evasion from NK cells.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates TLR4 ligand binding and signaling.", "mechanism": "Platelet TLR4 binds LPS, promotes neutrophil extracellular trap formation and bacterial trapping.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Viral infections (encephalomyocarditis)", "glycan_involvement": "Glycosylation influences receptor trafficking and function.", "mechanism": "Platelet TLR7 activation enhances platelet-neutrophil aggregates, improving viral clearance.", "protein": "TLR7", "relationship_type": "protective", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Viral and bacterial infections", "glycan_involvement": "Glycosylation required for ligand binding and immune modulation.", "mechanism": "GPIb mediates platelet-bacteria interaction, directing pathogens to dendritic cells for T-cell activation.", "protein": "GPIb", "relationship_type": "causal", "source_pmcid": "PMC12137170" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation critical for selectin-eosinophil interaction.", "mechanism": "Platelet P-selectin activates eosinophil \u03b21-integrin, promoting migration and inflammation.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137170" }, { "confidence": "high", "disease": "Ovarian cancer (OC)", "glycan_involvement": "Aberrant O-glycosylation exposes tumor-specific epitopes.", "mechanism": "Tumor antigen recognized by T cells; overexpressed in OC, used for immunotherapy targeting.", "protein": "Mucin 1 (MUC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137288" }, { "confidence": "high", "disease": "Ovarian cancer (OC)", "glycan_involvement": "O-glycosylation critical for PDPN function and immune modulation.", "mechanism": "PDPN+ cancer-associated fibroblasts (CAFs) regulate tumor development and immune cell activity; associated with malformed TLS and early relapse.", "protein": "Podoplanin (PDPN)", "protein_enriched": { "function": "Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activatio", "gene_name": "PDPN", "glycan_count": 6, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G29068FM", "G43417UB", "G56682BC", "G57321FI", "G01614ZM", "G49108TO" ], "uniprot_id": "Q86YL7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Ovarian cancer (OC)", "glycan_involvement": "Sulfated O-glycans required for lymphocyte binding.", "mechanism": "Marker of high endothelial venules (HEV) in TLS; facilitates lymphocyte trafficking into tumors.", "protein": "Peripheral node addressin (PNAd)", "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Ovarian cancer (OC)", "glycan_involvement": "N-glycosylation affects trafficking and function.", "mechanism": "Expressed by mature dendritic cells in TLS; involved in antigen presentation.", "protein": "DC-LAMP (CD208)", "protein_enriched": { "function": "Transcriptional factor (PubMed:16339272, PubMed:9774444). Plays a critical role in neuronal morphogenesis and survival of sensory neurons (By similarity). Represses the corneal epithelium differentiat", "gene_name": "KLF7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O75840" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Ovarian cancer (OC)", "glycan_involvement": "N-glycosylation modulates ligand-receptor interactions.", "mechanism": "Interacts with TIGIT on lymphocytes to suppress T/NK cell function; blockade enhances TLS and antitumor immunity.", "protein": "CD155 (PVR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Endometrial cancer (EC)", "glycan_involvement": "N-glycosylation regulates cell adhesion and immune cell interactions.", "mechanism": "Associated with mature TLS and antibody-secreting cells; correlates with prognosis.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Ovarian cancer (OC)", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "Upregulated in TLS-associated fibroblasts; facilitates immune cell adhesion and TLS structure.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Ovarian cancer (OC)", "glycan_involvement": "N-glycosylation essential for function.", "mechanism": "Upregulated in TLS formation; promotes lymphocyte adhesion and migration.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "high", "disease": "Ovarian cancer (OC)", "glycan_involvement": "N-glycosylation affects surface expression.", "mechanism": "B cell marker in TLS; presence correlates with improved survival and antitumor immunity.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "medium", "disease": "Sjogren syndrome (SjS)", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Marker of follicular dendritic cells in mature TLS; associated with autoimmunity and B cell hyperactivity.", "protein": "CD23", "relationship_type": "biomarker", "source_pmcid": "PMC12137288" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Not specified; glycosylation may affect trafficking and stability.", "mechanism": "HPV E5/E6 proteins suppress Cx43 phosphorylation and expression, impairing gap junctions and innate immunity, promoting cancer progression.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "causal", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Neurocognitive disorders (HIV-associated)", "glycan_involvement": "Not specified; glycosylation may regulate channel function.", "mechanism": "HIV gp120 increases Cx43 hemichannel activity, facilitating toxic ATP/Ca2+/NO transfer, leading to neuroinflammation.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "causal", "source_pmcid": "PMC12137313" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Not specified.", "mechanism": "Cx43-dependent mitochondrial transfer from BMSCs to alveolar cells protects against injury.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "protective", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Cx43 hemichannel inhibitors (TAT-GAP19, Peptide 5) reduce ATP release and inflammation, protecting against fibrosis.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Not specified.", "mechanism": "Cx43 inhibitors (Gap26, GAP19, Peptide5) reduce neuronal damage by modulating hemichannel activity.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137313" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Not specified.", "mechanism": "Inhibiting Cx43-dependent ATP release in macrophages improves sepsis outcome.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Keratinizing skin disorders (keratoderma, ectodermal dysplasia)", "glycan_involvement": "Not specified.", "mechanism": "Cx26 deficiency impairs epidermal barrier and innate immune defense.", "protein": "Connexin 26 (Cx26)", "protein_enriched": { "function": "Structural component of gap junctions (PubMed:16849369, PubMed:17551008, PubMed:19340074, PubMed:19384972, PubMed:21094651, PubMed:26753910). Gap junctions are dodecameric channels that connect the cy", "gene_name": "GJB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P29033" }, "relationship_type": "causal", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Cataracts", "glycan_involvement": "Not specified.", "mechanism": "Cx46 deficiency disrupts lens homeostasis, leading to cataract formation.", "protein": "Connexin 46 (Cx46)", "protein_enriched": { "function": "Structural component of lens fiber gap junctions (PubMed:30044662). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells (By similarity). They are formed by the docking", "gene_name": "GJA3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6H8" }, "relationship_type": "causal", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "Brain metastasis (breast/lung cancer)", "glycan_involvement": "Not specified.", "mechanism": "Cx43-mediated gap junctions enable cGAMP transfer from cancer cells to astrocytes, activating inflammatory pathways and promoting metastasis and chemoresistance.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "causal", "source_pmcid": "PMC12137313" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "Not specified.", "mechanism": "Cx43 upregulation in bone/joint cells drives inflammatory cytokine expression; siRNA targeting Cx43 alleviates arthritis.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137313" }, { "confidence": "high", "disease": "LCA1 subtype", "glycan_involvement": "Indirect; NSD1 mutations affect methylation, which can alter glycosylation patterns.", "mechanism": "High-frequency nonsense mutations in NSD1 lead to genome-wide hypomethylation, reduced immune infiltration, and better prognosis.", "protein": "NSD1", "protein_enriched": { "function": "Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the ce", "gene_name": "NSD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96L73" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12137314" }, { "confidence": "medium", "disease": "Laryngeal cancer (LCA)", "glycan_involvement": "Direct; modifies heparan sulfate glycosaminoglycans.", "mechanism": "HS3ST2 is a risk factor in the prognostic model; involved in heparan sulfate modification, which can affect tumor invasion.", "protein": "HS3ST2", "protein_enriched": { "function": "Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a se", "gene_name": "INPP5F", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q9Y2H2" }, "relationship_type": "biomarker/risk factor", "source_pmcid": "PMC12137314" }, { "confidence": "high", "disease": "LCA2 subtype", "glycan_involvement": "PD-L1 is a heavily glycosylated immune checkpoint protein; glycosylation stabilizes its cell surface expression.", "mechanism": "Elevated expression in LCA2 correlates with higher immune suppression and poor prognosis.", "protein": "CD274 (PD-L1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137314" }, { "confidence": "medium", "disease": "LCA2 subtype", "glycan_involvement": "PD-L2 is glycosylated, which affects its interaction with PD-1.", "mechanism": "Upregulated in LCA2, contributing to immune evasion.", "protein": "PDCD1LG2 (PD-L2)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137314" }, { "confidence": "medium", "disease": "LCA2 subtype", "glycan_involvement": "TIM-3 glycosylation modulates ligand binding and immune regulation.", "mechanism": "Higher expression in LCA2, associated with T cell inhibition and immune escape.", "protein": "HAVCR2 (TIM-3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137314" }, { "confidence": "medium", "disease": "LCA2 subtype", "glycan_involvement": "LAIR1 is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Upregulated in LCA2, contributing to immunosuppression.", "protein": "LAIR1", "protein_enriched": { "function": "Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation result", "gene_name": "LAIR1", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G03382KH", "G05962QB", "G06110VR", "G06330RB", "G11629QQ", "G15169WU", "G22310AV", "G25418HZ", "G32788FZ", "G45395BF", "G51413EV", "G57776ZS", "G62765YT", "G70232NH", "G79666IR", "G80075MS", "G81263BG", "G81637OR", "G84452RH", "G92275SC" ], "uniprot_id": "Q6GTX8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137314" }, { "confidence": "medium", "disease": "LCA2 subtype", "glycan_involvement": "BTLA glycosylation influences its inhibitory signaling.", "mechanism": "Elevated in LCA2, mediates immune inhibition.", "protein": "BTLA", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137314" }, { "confidence": "low", "disease": "Laryngeal cancer (LCA)", "glycan_involvement": "ABCF2 is glycosylated; glycosylation may affect transporter function.", "mechanism": "ABCF2 is a protective factor in the prognostic model; may influence drug resistance.", "protein": "ABCF2", "protein_enriched": { "function": "ATP-dependent low-affinity peptide transporter which translocates a broad spectrum of peptides from the cytosol to the lysosomal lumen for degradation (PubMed:15863492, PubMed:17977821, PubMed:1843430", "gene_name": "ABCB9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP78" }, "relationship_type": "protective", "source_pmcid": "PMC12137314" }, { "confidence": "low", "disease": "Laryngeal cancer (LCA)", "glycan_involvement": "TRPC1 is glycosylated; glycosylation may regulate channel activity.", "mechanism": "TRPC1 is a risk factor in the prognostic model; involved in calcium signaling.", "protein": "TRPC1", "protein_enriched": { "function": "Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:125942", "gene_name": "TRPM2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92275SC" ], "uniprot_id": "O94759" }, "relationship_type": "risk factor", "source_pmcid": "PMC12137314" }, { "confidence": "low", "disease": "Laryngeal cancer (LCA)", "glycan_involvement": "EPHX2 is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "EPHX2 is a protective factor in the prognostic model; involved in lipid metabolism.", "protein": "EPHX2", "protein_enriched": { "function": "Bifunctional enzyme (PubMed:12574510). The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:12574510, PubMed:12869654, PubMed:22", "gene_name": "EPHX2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P34913" }, "relationship_type": "protective", "source_pmcid": "PMC12137314" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects its antigenicity and immune recognition.", "mechanism": "Loss of MOG expression indicates demyelination in MS and experimental models.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "high", "disease": "Inflammatory Demyelinating Diseases", "glycan_involvement": "Glycosylation modulates MOG's immune interactions.", "mechanism": "Reduced MOG levels correlate with demyelination in IDDs.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "MBP is not glycosylated; no direct glycan involvement.", "mechanism": "Decreased MBP expression reflects myelin loss in MS and models.", "protein": "Myelin Basic Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "high", "disease": "Inflammatory Demyelinating Diseases", "glycan_involvement": "No glycan involvement.", "mechanism": "MBP reduction is a marker of demyelination in IDDs.", "protein": "Myelin Basic Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation may affect MOG's function and remyelination.", "mechanism": "Restoration of MOG expression is used to assess remyelination therapies.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137318" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "GFAP is not glycosylated.", "mechanism": "Increased GFAP indicates astroglial activation in demyelination.", "protein": "Glial Fibrillary Acidic Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation influences MOG's antigenicity.", "mechanism": "Autoimmune targeting of MOG contributes to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12137318" }, { "confidence": "medium", "disease": "Inflammatory Demyelinating Diseases", "glycan_involvement": "Glycosylation may affect therapeutic efficacy.", "mechanism": "MOG levels are used to evaluate remyelination strategies.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137318" }, { "confidence": "medium", "disease": "Inflammatory Demyelinating Diseases", "glycan_involvement": "No glycan involvement.", "mechanism": "GFAP upregulation marks astrocyte response in demyelination.", "protein": "Glial Fibrillary Acidic Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation affects MOG's detection and immune response.", "mechanism": "MOG reduction is used to quantify demyelination in ex vivo models.", "protein": "Myelin Oligodendrocyte Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12137318" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "ALG3 mediates N-glycosylation of proteins, impacting tumor progression.", "mechanism": "High ALG3 expression correlates with poor prognosis, larger tumor size, advanced stage, and microvascular invasion.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation by ALG3 stabilizes immune checkpoint proteins and alters immune cell infiltration.", "mechanism": "ALG3 overexpression mediates resistance to PD-1 blockade by promoting immune evasion.", "protein": "ALG3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates immune cell recruitment and function.", "mechanism": "ALG3 increases Treg infiltration, suppressing CD8+ T cell activity and promoting immune escape.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation affects macrophage polarization and recruitment.", "mechanism": "ALG3 reduces CD68+CD86+ macrophage infiltration, weakening anti-tumor immunity.", "protein": "ALG3", "relationship_type": "causal", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation by ALG3 affects PD-L1 stability and immune checkpoint function.", "mechanism": "High ALG3 predicts resistance to PD-1 inhibitors in patient-derived organoid models.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "PD-L1 glycosylation (mediated by ALG3) stabilizes its membrane localization.", "mechanism": "PD-L1 expression is positively correlated with ALG3, contributing to immune evasion.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12137335" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "ALG3-mediated glycosylation may regulate OX40 activity.", "mechanism": "ALG3 expression correlates with OX40, potentially limiting T cell function and promoting immunosuppression.", "protein": "OX40", "protein_enriched": { "function": "Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity", "gene_name": "TNFRSF4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43489" }, "relationship_type": "causal", "source_pmcid": "PMC12137335" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "ALG3 suppresses chemotactic factor secretion via N-glycosylation, reducing CD8+ T cell infiltration.", "mechanism": "High ALG3 expression correlates with poor prognosis and immune evasion.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC12137335" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation by ALG3 affects protein function in tumor cells.", "mechanism": "ALG3 is abnormally expressed and may contribute to tumor progression.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC12137335" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation by ALG3 affects protein function in tumor cells.", "mechanism": "ALG3 is abnormally expressed and may contribute to tumor progression.", "protein": "ALG3", "relationship_type": "biomarker", "source_pmcid": "PMC12137335" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects receptor folding and function.", "mechanism": "Decreased phosphorylation impairs insulin signaling, leading to reduced glucose uptake.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12137338" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycoprotein components of HDL modulate its function.", "mechanism": "HDL-C mediates reverse cholesterol transport and has antioxidant/anti-inflammatory effects.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12137338" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation of apolipoproteins affects lipoprotein metabolism.", "mechanism": "Elevated TG disrupts glucose metabolism and inhibits insulin action.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Multiple organ failure", "glycan_involvement": "CRP is a glycoprotein; glycosylation modulates its immune activity.", "mechanism": "CRP is elevated in inflammation and predicts poor outcomes in critical illness.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Cardiogenic shock", "glycan_involvement": "Glycosylation affects albumin stability and function.", "mechanism": "Low albumin is associated with poor prognosis in VA-ECMO patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates cytokine secretion and receptor binding.", "mechanism": "IL-6 is elevated in sepsis and correlates with disease severity.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation regulates platelet adhesion and aggregation.", "mechanism": "Platelet count and function are altered in cardiovascular events.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for proper GLUT4 trafficking.", "mechanism": "Impaired GLUT4 translocation reduces glucose uptake in insulin resistance.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC12137338" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Proinsulin glycosylation affects insulin maturation.", "mechanism": "Insulin deficiency or resistance is central to diabetes pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137338" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates ApoA-I stability and function.", "mechanism": "ApoA-I is a major HDL component, promoting cholesterol efflux.", "protein": "Apolipoprotein A-I", "relationship_type": "protective", "source_pmcid": "PMC12137338" }, { "confidence": "high", "disease": "Immunotherapeutic resistance", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation stabilizes PD-L1 and enhances immune evasion.", "mechanism": "Exosomal PD-L1 suppresses CD8+ T cell activity, mimicking immune checkpoint interactions and reducing efficacy of immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "MUC1 is heavily O-glycosylated, which is critical for its immune masking function.", "mechanism": "EVs shed MUC1, masking tumor antigens and reducing T cell recognition.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "HER2 is N-glycosylated, affecting its stability and immune recognition.", "mechanism": "EVs shed HER2, decreasing antigen availability for dendritic cell priming and adaptive immune activation.", "protein": "HER2", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "high", "disease": "Immunotherapeutic resistance", "glycan_involvement": "TGF-\u03b2 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "EVs deliver TGF-\u03b2, expanding Tregs and MDSCs, creating an immunosuppressive tumor microenvironment.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "CD133 is N-glycosylated, which is essential for its function and EV incorporation.", "mechanism": "CD133-containing microvesicles promote M2-like polarization of tumor-associated macrophages, supporting cancer progression and resistance.", "protein": "CD133", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Annexin A6 is a glycoprotein; glycosylation may affect its membrane association.", "mechanism": "CAFs secrete EVs rich in annexin A6, stabilizing \u03b21 integrin and upregulating FAK-YAP, enhancing survival post-cisplatin.", "protein": "Annexin A6", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "ANXA6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08133" }, "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "FMO2 is a glycoprotein; glycosylation may affect its stability.", "mechanism": "CAF-derived FMO2 in EVs facilitates lymphocyte infiltration; higher FMO2 correlates with worse prognosis.", "protein": "FMO2", "protein_enriched": { "function": "Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds (PubMed:10759686, PubMed:30381441, P", "gene_name": "FMO3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P31513" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137360" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "P-gp is N-glycosylated, which is important for its trafficking and function.", "mechanism": "Exosomal transfer of P-gp induces chemoresistant phenotype in breast cancer cells.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "MRP2 is N-glycosylated, affecting its localization and function.", "mechanism": "Exosomes from cisplatin-resistant ovarian cancer cells contain MRP2, contributing to drug efflux and resistance.", "protein": "MRP2", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "Selectins require glycosylation for ligand binding and function.", "mechanism": "Microvesicle-specific selectins mediate cell adhesion and may facilitate immune cell recruitment or evasion.", "protein": "Selectins", "relationship_type": "causal", "source_pmcid": "PMC12137360" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "S100A8 is a glycoprotein; glycosylation may affect stability and immune recognition.", "mechanism": "Elevated in RA; regulates cell cycle, neutrophil activation, and inflammation; correlates with disease activity.", "protein": "S100A8", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Enriched in SLE pathways; involved in inflammation.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Promotes oxidative stress and telomere damage via neutrophil activation.", "protein": "S100A8", "relationship_type": "causal", "source_pmcid": "PMC12137363" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "ABCC4 glycosylation affects membrane localization and drug transport.", "mechanism": "Transports drugs (e.g., methotrexate); inhibition enhances anti-inflammatory response.", "protein": "ABCC4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Allograft rejection", "glycan_involvement": "Glycosylation may regulate transporter activity.", "mechanism": "Enriched in allograft rejection pathways; may modulate immune cell function.", "protein": "ABCC4", "relationship_type": "biomarker", "source_pmcid": "PMC12137363" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "ISG20 is glycosylated; may affect stability and localization.", "mechanism": "Elevated in RA synovial macrophages; regulates RNA degradation and telomere maintenance.", "protein": "ISG20", "protein_enriched": { "function": "Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA (PubMed:11401564, PubMed:12594219, PubMed:16033969). Exhibits antiviral activity against RNA viruses including hepa", "gene_name": "ISG20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96AZ6" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect kinase activity.", "mechanism": "Promotes cell survival, proliferation, and IL-6 expression; maintains telomere stability.", "protein": "PIM2", "protein_enriched": { "function": "Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regula", "gene_name": "PIM2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9P1W9" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may influence SNARE complex formation.", "mechanism": "Downregulated in RA; may contribute to neuropathy and pain via synaptic vesicle trafficking.", "protein": "VAMP2", "relationship_type": "biomarker", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Allograft rejection", "glycan_involvement": "Glycosylation may modulate immune cell interactions.", "mechanism": "Enriched in allograft rejection pathways; involved in immune activation.", "protein": "S100A8", "relationship_type": "biomarker", "source_pmcid": "PMC12137363" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation impacts drug efflux.", "mechanism": "Enriched in SLE pathways; may affect drug response.", "protein": "ABCC4", "relationship_type": "biomarker", "source_pmcid": "PMC12137363" }, { "confidence": "high", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "FGF-21 is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Circulating FGF-21 levels are elevated in NAFLD patients, especially in advanced stages.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "high", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may modulate FGF-21 receptor interactions.", "mechanism": "FGF-21 levels are significantly higher in NASH compared to controls, indicating disease severity.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "high", "disease": "NASH-related Cirrhosis", "glycan_involvement": "Glycosylation may influence FGF-21 half-life and activity.", "mechanism": "FGF-21 levels are highest in NASH-related cirrhosis, suggesting a compensatory response or resistance.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect FGF-21's metabolic signaling.", "mechanism": "FGF-21 levels are positively associated with T2DM prevalence in NAFLD cohorts.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may regulate FGF-21 secretion in adipose tissue.", "mechanism": "FGF-21 is elevated in obesity and may reflect metabolic stress.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "high", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation of analogs may affect pharmacokinetics and efficacy.", "mechanism": "FGF-21 analogs (e.g., pegbelfermin, efruxifermin) are under clinical investigation for NASH treatment.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate FGF-21's receptor binding and signaling.", "mechanism": "FGF-21 may protect against hepatic steatosis by promoting fatty acid oxidation and reducing lipogenesis.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "causal/protective", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may influence FGF-21's anti-inflammatory activity.", "mechanism": "FGF-21 may attenuate hepatic inflammation and fibrosis via anti-inflammatory and anti-fibrotic pathways.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "causal/protective", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may affect assay detection and diagnostic accuracy.", "mechanism": "FGF-21 has moderate sensitivity and specificity for non-invasive NASH diagnosis.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "biomarker", "source_pmcid": "PMC12137391" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation of analogs may impact therapeutic potential.", "mechanism": "FGF-21 analogs may improve insulin sensitivity and metabolic parameters in T2DM.", "protein": "Fibroblast Growth Factor-21 (FGF-21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137391" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "BDNF is a glycoprotein; glycosylation may affect its stability and secretion, but not directly discussed.", "mechanism": "Low BDNF levels are associated with MS progression and relapses; BDNF may reflect neurodegeneration and repair.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "biomarker", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "BDNF glycosylation could modulate its neuroprotective effects, but not directly addressed.", "mechanism": "Exercise-induced BDNF increase may promote neuroprotection, synaptic plasticity, and remyelination.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "protective", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Not specified.", "mechanism": "Low BDNF levels are found in dementia, indicating neurodegeneration.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "biomarker", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Not specified.", "mechanism": "Low BDNF levels are associated with depression.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "biomarker", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "Not specified.", "mechanism": "Low BDNF levels are found in ALS, reflecting neurodegeneration.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "biomarker", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Not specified.", "mechanism": "Low BDNF levels are found in Alzheimer\u2019s disease.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "biomarker", "source_pmcid": "PMC12137578" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "BDNF glycosylation may influence therapeutic efficacy, but not directly discussed.", "mechanism": "Physical exercise increases BDNF, which may be leveraged as a therapeutic strategy for MS.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137578" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "Not specified.", "mechanism": "BDNF may compensate for glial and neuronal damage during demyelination.", "protein": "Brain-derived neurotrophic factor", "relationship_type": "causal", "source_pmcid": "PMC12137578" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "No direct glycosylation involvement; acts as a methylation reader affecting gene expression.", "mechanism": "MBD2 is upregulated in B cells in SLE, promotes B cell differentiation and activation, enhances BCR signaling, and drives autoantibody production via the LEF-1-PTEN-PI3K axis.", "protein": "Methyl-CpG-binding domain protein 2 (MBD2)", "relationship_type": "causal", "source_pmcid": "PMC12137598" }, { "confidence": "high", "disease": "Lupus nephritis (renal injury in SLE)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MBD2 expression is higher in B cells from SLE patients with renal injury; correlates with disease activity.", "protein": "Methyl-CpG-binding domain protein 2 (MBD2)", "relationship_type": "biomarker", "source_pmcid": "PMC12137598" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "PTEN is a glycoprotein, but glycosylation not discussed in this context.", "mechanism": "PTEN is downregulated in SLE B cells; its loss leads to increased PI3K signaling and B cell hyperactivation.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "protective", "source_pmcid": "PMC12137598" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "LEF-1 is a glycoprotein, but glycosylation not discussed in this context.", "mechanism": "LEF-1 is suppressed by MBD2 in SLE B cells; LEF-1 normally promotes PTEN expression, restraining B cell activation.", "protein": "LEF-1", "protein_enriched": { "function": "Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence o", "gene_name": "LEF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70101JE", "G80920RR" ], "uniprot_id": "Q9UJU2" }, "relationship_type": "protective", "source_pmcid": "PMC12137598" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "PI3K is a glycoprotein, but glycosylation not discussed in this context.", "mechanism": "PI3K signaling is upregulated due to MBD2-mediated suppression of PTEN, promoting B cell activation and SLE pathogenesis.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137598" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "BCR is a heavily glycosylated immunoglobulin complex; glycosylation not specifically discussed here.", "mechanism": "BCR signaling is enhanced by MBD2 activity, leading to increased B cell activation and autoantibody production.", "protein": "B cell receptor (BCR)", "relationship_type": "causal", "source_pmcid": "PMC12137598" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MBD2 deficiency or inhibition reduces lupus symptoms, GC response, and autoantibody production in mouse models.", "protein": "Methyl-CpG-binding domain protein 2 (MBD2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137598" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Not discussed.", "mechanism": "LEF-1 is downregulated in SLE B cells due to promoter methylation and MBD2 binding.", "protein": "LEF-1", "protein_enriched": { "function": "Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence o", "gene_name": "LEF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70101JE", "G80920RR" ], "uniprot_id": "Q9UJU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137598" }, { "confidence": "medium", "disease": "Lupus nephritis (renal injury in SLE)", "glycan_involvement": "Not discussed.", "mechanism": "PTEN expression is reduced in B cells from SLE patients with renal injury.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137598" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "MBD2 expression in B cells correlates with SLE disease activity index (SLEDAI).", "protein": "Methyl-CpG-binding domain protein 2 (MBD2)", "relationship_type": "biomarker", "source_pmcid": "PMC12137598" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects receptor stability and signaling.", "mechanism": "AdipoR2 enhances insulin sensitivity and fatty acid oxidation, counteracting lipid accumulation and insulin resistance.", "protein": "Adiponectin receptor 2 (AdipoR2)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix (By similarity). Fibrin has a major function in hemostasis as one of the primary componen", "gene_name": "Fgg", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8VCM7" }, "relationship_type": "protective", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation required for secretion and chemotactic activity.", "mechanism": "Ccl2 recruits monocytes/macrophages, driving hepatic inflammation and damage.", "protein": "Ccl2 (MCP-1)", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ion", "gene_name": "Ccl2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P10148" }, "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates chemokine gradient formation.", "mechanism": "Cxcl10 promotes immune cell recruitment, exacerbating liver inflammation and fibrosis.", "protein": "Cxcl10", "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 mediates hepatocyte apoptosis and inflammation, advancing MASLD to MASH.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation required for maturation and secretion.", "mechanism": "IL-1\u03b2 drives pro-inflammatory signaling and hepatocyte injury.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation affects stability and inhibitory activity.", "mechanism": "Elevated PAI-1 indicates progression from MASLD to MASH.", "protein": "Serpine1/PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation essential for enzymatic activity.", "mechanism": "Increased Lpl expression correlates with hepatic fatty acid accumulation.", "protein": "Lpl", "relationship_type": "biomarker", "source_pmcid": "PMC12137631" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect nuclear localization and transcriptional activity.", "mechanism": "Ppar\u03b3 upregulation promotes de novo lipogenesis and lipid accumulation.", "protein": "Ppar\u03b3", "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "Abcg1 dysfunction impairs cholesterol efflux, contributing to hepatic steatosis.", "protein": "Abcg1", "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates phosphatase activity and stability.", "mechanism": "PTPN1 suppresses insulin signaling, promoting hepatic insulin resistance and MASLD progression.", "protein": "PTPN1", "relationship_type": "causal", "source_pmcid": "PMC12137631" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "No direct glycosylation; metabolic enzyme involved in glycan catabolism.", "mechanism": "GLYCTK2 is overexpressed in GBM and promotes tumorigenesis by enabling fructolytic adaptation under glucose deprivation.", "protein": "GLYCTK2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "No direct glycosylation; role in fructose (glycan) metabolism.", "mechanism": "GLYCTK2 depletion impairs GBM cell survival under glucose deprivation, indicating a causal role in metabolic adaptation.", "protein": "GLYCTK2", "relationship_type": "causal", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Indirect; facilitates fructose utilization (glycan catabolism).", "mechanism": "GLYCTK2 enables GBM cells to survive glucose deprivation by promoting fructose-dependent metabolic flux.", "protein": "GLYCTK2", "relationship_type": "protective", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "D-Glyceric Acidemia/Aciduria", "glycan_involvement": "No direct glycosylation; enzyme in glycan breakdown.", "mechanism": "GLYCTK2 inactivation leads to glycerate accumulation and metabolic acidosis.", "protein": "GLYCTK2", "relationship_type": "causal", "source_pmcid": "PMC12137673" }, { "confidence": "medium", "disease": "Colon adenocarcinoma", "glycan_involvement": "No direct glycosylation; metabolic enzyme.", "mechanism": "GLYCTK2 is upregulated in colon adenocarcinoma tissues.", "protein": "GLYCTK2", "relationship_type": "biomarker", "source_pmcid": "PMC12137673" }, { "confidence": "medium", "disease": "Brain lower-grade glioma (LGG)", "glycan_involvement": "No direct glycosylation; metabolic enzyme.", "mechanism": "GLYCTK2 is upregulated in LGG tissues.", "protein": "GLYCTK2", "relationship_type": "biomarker", "source_pmcid": "PMC12137673" }, { "confidence": "medium", "disease": "Rectum adenocarcinoma", "glycan_involvement": "No direct glycosylation; metabolic enzyme.", "mechanism": "GLYCTK2 is upregulated in rectum adenocarcinoma tissues.", "protein": "GLYCTK2", "relationship_type": "biomarker", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "No direct glycosylation; protein-protein interaction.", "mechanism": "STUB1 mediates ubiquitination and degradation of GLYCTK2, limiting its stability and GBM cell survival under glucose deprivation.", "protein": "STUB1", "relationship_type": "regulatory", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "No direct glycosylation; post-translational phosphorylation.", "mechanism": "ERK1 phosphorylates GLYCTK2 at S220, stabilizing it and promoting GBM survival under glucose deprivation.", "protein": "ERK1", "relationship_type": "regulatory", "source_pmcid": "PMC12137673" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Potential glycosylation as a membrane transporter, but not discussed in this article.", "mechanism": "SLC2A5 is upregulated under glucose deprivation, supporting fructose uptake for GBM survival.", "protein": "SLC2A5 (GLUT5)", "protein_enriched": { "function": "Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis", "gene_name": "LRP1B", "glycan_count": 17, "glycosylation_sites_count": 46, "glytoucan_ids": [ "G80920RR", "G41247ZX", "G49108TO", "G46503DX", "G71142DF", "G05724UK", "G06110VR", "G39188ZX", "G70101JE", "G57321FI", "G62765YT", "G25079LO", "G08290VR", "G31852PQ", "G46910OC", "G83460ZZ", "G59924QI" ], "uniprot_id": "Q9NZR2" }, "relationship_type": "supportive", "source_pmcid": "PMC12137673" }, { "confidence": "high", "disease": "Diabetic complications", "glycan_involvement": "RAGE is a glycoprotein; glycosylation affects ligand binding and signaling.", "mechanism": "AGEs bind RAGE, activating inflammatory and oxidative stress pathways leading to vascular damage.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12137698" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "AGEs are glycated proteins; glycation disrupts normal glycoprotein function.", "mechanism": "AGEs accumulate and modify endothelial proteins, impairing function and promoting inflammation.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12137698" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "NF\u03baB1 activation downstream of glycoprotein signaling.", "mechanism": "AGEs-RAGE interaction activates NF\u03baB1, upregulating pro-inflammatory gene expression.", "protein": "NF\u03baB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137698" }, { "confidence": "medium", "disease": "Diabetic complications", "glycan_involvement": "PIK3 pathway modulated by glycoprotein receptor signaling.", "mechanism": "PIK3 is activated downstream of AGEs-RAGE, affecting cell survival and metabolism.", "protein": "PIK3 (PI3K)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137698" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-1\u03b2 is a glycoprotein cytokine; glycosylation affects secretion and activity.", "mechanism": "Upregulated by AGEs-RAGE signaling, indicating inflammatory response.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137698" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "TNF\u03b1 is a glycoprotein cytokine; glycosylation modulates function.", "mechanism": "Elevated in response to AGEs-RAGE activation, mediates inflammation.", "protein": "TNF\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12137698" }, { "confidence": "medium", "disease": "Impaired neovascularization", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation required for secretion and activity.", "mechanism": "PL restores TGF-\u03b21 levels reduced by AGEs, promoting cell proliferation and vascular repair.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective", "source_pmcid": "PMC12137698" }, { "confidence": "medium", "disease": "Refractory wounds", "glycan_involvement": "HEC1 function may be modulated by glycosylation.", "mechanism": "PL reverses AGEs-induced reduction of HEC1, supporting mitosis and cell survival.", "protein": "HEC1", "relationship_type": "protective", "source_pmcid": "PMC12137698" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycation of vascular glycoproteins impairs function.", "mechanism": "AGEs accumulation in vasculature leads to loss of elasticity and hemodynamic dysfunction.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12137698" }, { "confidence": "medium", "disease": "Innate immunity dysfunction", "glycan_involvement": "RAGE glycosylation affects immune signaling.", "mechanism": "Excess AGEs upregulate RAGE, potentially interfering with its role in pattern recognition and immunity.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12137698" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects stability and ER localization.", "mechanism": "Rate-limiting enzyme in cholesterol biosynthesis; dysregulation leads to hypercholesterolemia and CVD.", "protein": "HMG-CoA reductase (Hmgcr)", "protein_enriched": { "function": "One of the primary rRNA binding proteins, it binds directly to 3'-end of the 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to th", "gene_name": "rpsG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17291" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Reduced Hmgcr expression under hypoxia lowers cholesterol, impacting plaque formation.", "protein": "HMG-CoA reductase (Hmgcr)", "protein_enriched": { "function": "One of the primary rRNA binding proteins, it binds directly to 3'-end of the 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to th", "gene_name": "rpsG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17291" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "Cholesterol is precursor for corticosteroids, influencing blood pressure regulation.", "protein": "HMG-CoA reductase (Hmgcr)", "protein_enriched": { "function": "One of the primary rRNA binding proteins, it binds directly to 3'-end of the 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to th", "gene_name": "rpsG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17291" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may affect stability and transcriptional activity.", "mechanism": "Elevated under hypoxia, negatively regulates Hmgcr and Srebf, reducing cholesterol synthesis.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects nuclear translocation and activity.", "mechanism": "Transcriptional activator of Hmgcr; reduced under hypoxia, lowering cholesterol biosynthesis.", "protein": "SREBF (Srebf/SREBP)", "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may modulate DNA binding.", "mechanism": "Upregulated under hypoxia, represses Hmgcr transcription, reducing cholesterol.", "protein": "RUNX3", "protein_enriched": { "function": "Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3',", "gene_name": "RUNX3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13761" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation influences protein stability.", "mechanism": "Hypoxia-induced HIF-1\u03b1 promotes metabolic adaptation, including lipid metabolism changes.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Altered cholesterol biosynthesis contributes to metabolic syndrome.", "protein": "HMG-CoA reductase (Hmgcr)", "protein_enriched": { "function": "One of the primary rRNA binding proteins, it binds directly to 3'-end of the 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to th", "gene_name": "rpsG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17291" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "Dyslipidemia via Hmgcr impacts insulin sensitivity.", "protein": "HMG-CoA reductase (Hmgcr)", "protein_enriched": { "function": "One of the primary rRNA binding proteins, it binds directly to 3'-end of the 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to th", "gene_name": "rpsG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17291" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects transcriptional activity.", "mechanism": "Hypoxia-induced HIF-1\u03b1 alters lipid metabolism, contributing to plaque formation.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12137849" }, { "confidence": "medium", "disease": "Respiratory depression during procedural sedation", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and bioactivity.", "mechanism": "TSH included as a feature in predictive model; abnormal TSH may reflect underlying metabolic or respiratory risk.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12137915" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "N-glycosylation modulates ORM1's anti-inflammatory and immunomodulatory functions.", "mechanism": "ORM1 is upregulated in AMI plasma and unstable plaques, associated with inflammation, lipid localization, and foam cell differentiation.", "protein": "ORM1", "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "O-glycosylation affects SPP1's cell adhesion and immune activation properties.", "mechanism": "SPP1 is upregulated in AMI and atherosclerotic core macrophages, promoting inflammation and tissue remodeling.", "protein": "SPP1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "N-glycosylation required for lysosomal targeting and enzymatic activity.", "mechanism": "MANBA is upregulated in AMI plasma and atherosclerotic plaques, involved in lipid metabolism and apoptosis regulation.", "protein": "MANBA", "protein_enriched": { "function": "Catalyzes the synthesis of lactosylceramide (LacCer) via the transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) (PubMed:1551920, PubMed:24498430, PubMed:3099851). LacCer is the star", "gene_name": "B4GALT6", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G55101FB" ], "uniprot_id": "Q9UBX8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Putative N-glycosylation may affect vesicle trafficking and receptor-mediated endocytosis.", "mechanism": "CLTC is upregulated in AMI plasma and adjacent vascular regions, regulates endothelial migration and lipid storage.", "protein": "CLTC", "protein_enriched": { "function": "Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi ", "gene_name": "CLTC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q00610" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "No direct glycosylation; included for context.", "mechanism": "PSME1 is downregulated in AMI plasma and atherosclerotic core, modulates antigen processing and apoptosis.", "protein": "PSME1", "protein_enriched": { "function": "Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern o", "gene_name": "PSME1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q06323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Putative N-glycosylation may influence protein-protein interactions and cell migration.", "mechanism": "IQGAP1 is upregulated in AMI plasma and adjacent regions, controls cytoskeleton organization and vessel morphogenesis.", "protein": "IQGAP1", "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Putative O-glycosylation may regulate signaling and cell adhesion.", "mechanism": "CTNNB1 is upregulated in AMI plasma and adjacent regions, involved in Wnt signaling, wound healing, and DNA metabolism.", "protein": "CTNNB1", "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Putative O-glycosylation may modulate antimicrobial activity.", "mechanism": "CAMP is upregulated in AMI plasma, mediates innate immune responses and cholesterol efflux.", "protein": "CAMP", "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Putative N-glycosylation may affect RNA-binding and immune regulation.", "mechanism": "FUBP3 is downregulated in AMI plasma, associated with B cell immunity and inflammasome signaling.", "protein": "FUBP3", "protein_enriched": { "function": "May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression", "gene_name": "FUBP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96I24" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "high", "disease": "Plaque Instability", "glycan_involvement": "N-glycosylation modulates ORM1's anti-inflammatory properties and vascular interactions.", "mechanism": "ORM1 is elevated in unstable atherosclerotic plaques, indicating active inflammation and risk of rupture.", "protein": "ORM1", "relationship_type": "biomarker", "source_pmcid": "PMC12137932" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "CCR8 is a glycoprotein; glycosylation may affect receptor function and ligand binding.", "mechanism": "CCR8 mediates CCL1-driven infiltration and activation of monocytes/macrophages, promoting liver inflammation.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation may regulate CCR8 surface expression and signaling.", "mechanism": "CCR8 promotes monocyte infiltration and hepatic stellate cell activation, driving fibrogenesis.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "Chemokine glycosylation can modulate receptor interaction and chemotactic activity.", "mechanism": "CCL1 binds CCR8, recruiting monocytes to the liver and promoting inflammation.", "protein": "CCL1 (C-C motif chemokine ligand 1)", "protein_enriched": { "function": "Cytokine that is chemotactic for monocytes but not for neutrophils. Binds to CCR8", "gene_name": "CCL1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22362" }, "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation may influence CCR8 function in tissue infiltration.", "mechanism": "CCR8 mediates immune cell infiltration and myofibroblast-like differentiation in lung tissue.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation may affect CCR8 ligand binding and immune cell trafficking.", "mechanism": "CCR8 is implicated in Th2 cell recruitment and airway inflammation.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may modulate CCR8-mediated cell migration.", "mechanism": "CCR8 contributes to immune cell migration into the CNS, exacerbating neuroinflammation.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation could affect CCR8 stability and immune evasion.", "mechanism": "CCR8 is expressed on tumor-infiltrating immune cells and may regulate tumor microenvironment.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "Targeting glycosylated CCR8 may enhance therapeutic specificity.", "mechanism": "CCR8 antagonizing peptide (AP8ii) inhibits CCL1-driven monocyte infiltration, reducing inflammation and fibrosis.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Chemokine glycosylation can influence receptor interaction.", "mechanism": "CCL1-CCR8 axis drives monocyte recruitment and hepatic stellate cell activation.", "protein": "CCL1 (C-C motif chemokine ligand 1)", "protein_enriched": { "function": "Cytokine that is chemotactic for monocytes but not for neutrophils. Binds to CCR8", "gene_name": "CCL1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22362" }, "relationship_type": "causal", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation may be important for antagonist binding.", "mechanism": "CCR8 antagonism reduces monocyte infiltration and fibrogenesis in vivo.", "protein": "CCR8 (C-C chemokine receptor type 8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137978" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "CD4 is a glycoprotein; glycosylation affects its stability and immune function.", "mechanism": "Lentinan polysaccharide increases CD4 expression, improving immunity against HIV.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137980" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "SIgA is heavily glycosylated, essential for mucosal immunity.", "mechanism": "Chitosan adjuvants enhance mucosal SIgA production, improving defense against influenza.", "protein": "SIgA", "relationship_type": "protective", "source_pmcid": "PMC12137980" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Dectin-1 is a glycoprotein receptor for \u03b2-glucan.", "mechanism": "\u03b2-glucan interacts with Dectin-1 on immune cells, stimulating anti-tumor immunity.", "protein": "Dectin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137980" }, { "confidence": "medium", "disease": "Foot-and-mouth disease", "glycan_involvement": "Dectin-2 glycosylation affects ligand binding and immune activation.", "mechanism": "d-Galacto-D-mannan activates Dectin-2, generating cellular and humoral responses.", "protein": "Dectin-2", "protein_enriched": { "function": "Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: specifically recognizes and binds alpha-mannans on C.albicans hypheas (PubMed:23911656, PubMed:2", "gene_name": "CLEC6A", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q6EIG7" }, "relationship_type": "protective", "source_pmcid": "PMC12137980" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Fc gamma receptors are glycosylated, influencing antibody interactions.", "mechanism": "Astragalus polysaccharide modulates Fc gamma R-mediated phagocytosis, enhancing vaccine response.", "protein": "Fc gamma receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137980" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CD86 glycosylation modulates costimulatory signaling.", "mechanism": "Chitosan nanoparticles upregulate CD86 on DCs, boosting SARS-CoV-2 vaccine responses.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12137980" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "MBL glycosylation is critical for pathogen recognition.", "mechanism": "Mannan adjuvants stimulate complement pathway via mannan-binding lectin, enhancing anti-SARS-CoV-2 immunity.", "protein": "Mannan-binding lectin", "relationship_type": "protective", "source_pmcid": "PMC12137980" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "MHC II glycosylation affects peptide loading and immune recognition.", "mechanism": "Chitosan nanoparticles enhance antigen presentation via MHC II, promoting anti-tumor T cell responses.", "protein": "MHC II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137980" }, { "confidence": "medium", "disease": "Allergic asthma", "glycan_involvement": "DC-SIGN glycosylation modulates ligand binding.", "mechanism": "Mannan-decorated nanoparticles target DC-SIGN, inducing tolerogenic DCs and Treg cells to prevent asthma.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12137980" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Dectin-1 glycosylation affects immune cell targeting.", "mechanism": "\u03b2-glucan-based nanoparticles target Dectin-1+ monocytes/macrophages, suppressing NLRP3 inflammasome and preventing sepsis.", "protein": "Dectin-1", "relationship_type": "protective", "source_pmcid": "PMC12137980" }, { "confidence": "high", "disease": "Cerebral small vessel disease", "glycan_involvement": "Defective O-glycosylation of hydroxylysine residues", "mechanism": "COLGALT1 mutations impair collagen IV glycosylation and secretion", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "medium", "disease": "Autoimmune arthritis", "glycan_involvement": "O-glycosylation of hydroxylysine increases immunogenicity", "mechanism": "Glycosylated collagen IV enhances immune response in arthritis models", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "Fibrosis (liver, kidney, heart, lung, skin)", "glycan_involvement": "Altered glycosylation modulates collagen stability and deposition", "mechanism": "Excessive collagen I synthesis and glycosylation contribute to ECM accumulation", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "Keloid", "glycan_involvement": "Enhanced O-glycosylation promotes abnormal ECM", "mechanism": "Overproduction and abnormal glycosylation of collagen I in keloid fibroblasts", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12138068" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Altered O-glycosylation affects cartilage structure", "mechanism": "Abnormal glycosylation and expression of collagen II linked to cartilage fibrosis", "protein": "Collagen II", "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "O-glycosylation modulates cartilage matrix", "mechanism": "Increased collagen X expression and glycosylation in cartilage fibrosis", "protein": "Collagen X", "relationship_type": "biomarker", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation regulates integrin and receptor interactions", "mechanism": "Altered glycosylation and cross-linking of collagen I affect tumor microenvironment and metastasis", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "Ehlers\u2013Danlos syndrome", "glycan_involvement": "Defective O-glycosylation of hydroxylysine", "mechanism": "Lysyl hydroxylase mutations impair collagen glycosylation and cross-linking", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "Osteogenesis imperfecta", "glycan_involvement": "Impaired glycosylation of hydroxylysine/proline residues", "mechanism": "Prolyl 3-hydroxylase mutations disrupt collagen glycosylation and stability", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12138068" }, { "confidence": "medium", "disease": "Fibrosis (skin, lung, heart, etc.)", "glycan_involvement": "O-glycosylation affects ECM assembly", "mechanism": "Overproduction and altered glycosylation of collagen III in fibrotic tissues", "protein": "Collagen III", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A2", "glycan_count": 18, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G25637MV", "G27915IV", "G31852PQ", "G39188ZX", "G40574BA", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G43417UB", "G49108TO" ], "uniprot_id": "P08123" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12138068" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "No direct glycosylation mentioned; RNA recognition may be modulated by glycan environment.", "mechanism": "Recognizes CpG-rich viral RNA and promotes degradation, restricting viral replication.", "protein": "Zinc finger antiviral protein (ZAP)", "protein_enriched": { "function": "Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory comp", "gene_name": "SAP130", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9H0E3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "Dengue virus (DENV) infection", "glycan_involvement": "Glycosylation may affect chaperone activity and viral protein interactions.", "mechanism": "Facilitates viral entry, replication, assembly, and release; inhibitors block these stages.", "protein": "Heat shock protein 70 (Hsp70)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "HSV1, HSV2, HCMV, EBOV, HIV1, Influenza virus infections", "glycan_involvement": "Glycosylation may modulate chaperone-client interactions.", "mechanism": "Stabilizes viral proteins during replication and assembly; inhibitors reduce viral replication.", "protein": "Heat shock protein 90 (Hsp90)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "Rotavirus, Pestivirus, Pseudorabies virus, H1N1 IAV infections", "glycan_involvement": "Potential glycosylation affects nuclear localization and stability.", "mechanism": "Targeted by viral proteins for degradation or inhibition, suppressing IFN response.", "protein": "Interferon regulatory factor 3 (IRF3)", "relationship_type": "causal", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "Duck hepatitis A virus, Pseudorabies virus, H1N1 IAV infections", "glycan_involvement": "Potential glycosylation affects function.", "mechanism": "Viral proteins inhibit IRF7, reducing IFN production and antiviral defense.", "protein": "Interferon regulatory factor 7 (IRF7)", "protein_enriched": { "function": "Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:28342865, PubMed:2876885", "gene_name": "IRF7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92985" }, "relationship_type": "causal", "source_pmcid": "PMC12138082" }, { "confidence": "medium", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation may affect enzyme activity and virion incorporation.", "mechanism": "Incorporation into virions impairs tRNA packaging, reducing infectivity.", "protein": "Pyruvate kinase muscle type 2 (PKM2)", "relationship_type": "protective", "source_pmcid": "PMC12138082" }, { "confidence": "medium", "disease": "General viral infections (proviral effect)", "glycan_involvement": "Thrombin is N-glycosylated, affecting its activity and interactions.", "mechanism": "miR-214 upregulates thrombin, facilitating viral infection and suppressing antiviral factors.", "protein": "Thrombin", "relationship_type": "causal", "source_pmcid": "PMC12138082" }, { "confidence": "medium", "disease": "Influenza virus H1N1 infection", "glycan_involvement": "Glycosylation may regulate ATPase function.", "mechanism": "miR-1-3p inhibits ATP6V1A, reducing viral replication.", "protein": "ATP6V1A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "Influenza A virus (IAV) and RSV infections", "glycan_involvement": "Glycosylation may affect kinase activity.", "mechanism": "Targeted by miR-124, miR-24, miR-744, suppressing p38 MAPK pathway and viral replication.", "protein": "MAPK-activated protein kinase 2 (MK2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138082" }, { "confidence": "medium", "disease": "HCV, Sendai virus, Newcastle disease virus infections", "glycan_involvement": "Glycosylation may modulate adaptor function.", "mechanism": "Downregulation of miR-1225-3p increases GAB3, enhancing antiviral response.", "protein": "Growth factor receptor-bound protein 2-associated binding protein 3 (GAB3)", "protein_enriched": { "function": "DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hyb", "gene_name": "PIF1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H611" }, "relationship_type": "protective", "source_pmcid": "PMC12138082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BuChE is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "BuChE levels increase in AD; inhibition improves cognitive function and reduces amyloid aggregation.", "protein": "Butyrylcholinesterase (BuChE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138102" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AChE is glycosylated; glycosylation modulates enzyme activity.", "mechanism": "AChE levels decrease in AD; reduced cholinergic signaling contributes to cognitive decline.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "VLDLR is glycosylated; glycosylation required for receptor function.", "mechanism": "Upregulation by BuChE inhibitor 8e suggests modulation of Reelin pathway, supporting synaptic function.", "protein": "Very low-density lipoprotein receptor (VLDLR)", "relationship_type": "protective", "source_pmcid": "PMC12138102" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation influences processing and aggregation.", "mechanism": "APP overexpression and abnormal processing lead to amyloid-beta accumulation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "PS1 is glycosylated; glycosylation affects gamma-secretase activity.", "mechanism": "PS1 mutations increase amyloid-beta production; expression reduced by BuChE inhibitor 8e.", "protein": "Presenilin-1 (PS1)", "relationship_type": "causal", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "APOE glycosylation modulates lipid binding and amyloid interaction.", "mechanism": "APOE genotype influences amyloid deposition and clearance; expression reduced by BuChE inhibitor 8e.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "risk factor", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "Elevated IL-6 in AD models; BuChE inhibitor 8e reduces IL-6 expression, indicating anti-inflammatory effect.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "TNF-\u03b1 glycosylation influences receptor binding.", "mechanism": "TNF-\u03b1 upregulated in AD; BuChE inhibitor 8e lowers TNF-\u03b1, reducing inflammation.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-1\u03b2 glycosylation affects activity and secretion.", "mechanism": "IL-1\u03b2 increased in AD; BuChE inhibitor 8e decreases IL-1\u03b2, mitigating neuroinflammation.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138102" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Reelin is highly glycosylated; glycosylation essential for secretion and function.", "mechanism": "Reelin pathway modulated by BuChE inhibitor 8e via VLDLR upregulation, supporting synaptic plasticity.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "protective", "source_pmcid": "PMC12138102" }, { "confidence": "high", "disease": "Macrophage polarization (M2 phenotype)", "glycan_involvement": "N-glycosylation of CD206 is necessary for M2 polarization; glutaminolysis supports UDP-GlcNAc biosynthesis for N-glycosylation.", "mechanism": "CD206 is highly expressed on M2 macrophages; its N-glycosylation is required for surface expression and function.", "protein": "CD206 (mannose receptor)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "high", "disease": "Cancer (solid tumors)", "glycan_involvement": "No direct glycosylation; impacts glycoprotein biosynthesis via glutamine metabolism.", "mechanism": "GLS1 catalyzes glutaminolysis, fueling tumor growth and antioxidant defense; inhibition starves tumor cells and disrupts redox balance.", "protein": "GLS1 (Glutaminase 1)", "protein_enriched": { "function": "Receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response", "gene_name": "Ltb4r", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O88855" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138122" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "Indirect; affects glycoprotein synthesis in ECs via glutamine supply.", "mechanism": "GLS1-driven glutaminolysis in endothelial cells supports angiogenesis; inhibition normalizes vasculature.", "protein": "GLS1 (Glutaminase 1)", "protein_enriched": { "function": "Receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response", "gene_name": "Ltb4r", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O88855" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138122" }, { "confidence": "medium", "disease": "Pathological tumor vasculature", "glycan_involvement": "CD31 is N-glycosylated, affecting cell adhesion and trafficking.", "mechanism": "CD31 marks endothelial cells; reduced and normalized expression indicates vascular normalization after GLS1 inhibition.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "VEGF is glycosylated, which affects its secretion and receptor binding.", "mechanism": "VEGF drives pathological angiogenesis; its expression is reduced by GLS1 inhibition and vascular normalization.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12138122" }, { "confidence": "medium", "disease": "Immunogenic cell death (ICD) in cancer", "glycan_involvement": "CRT is glycosylated; glycosylation may affect its immunogenicity.", "mechanism": "Surface exposure of CRT is a hallmark of ICD, promoting dendritic cell activation and antitumor immunity.", "protein": "CRT (Calreticulin)", "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "medium", "disease": "Impaired antitumor immunity", "glycan_involvement": "CD86 is N-glycosylated, affecting its stability and immune signaling.", "mechanism": "CD86 upregulation marks dendritic cell maturation, enhancing T cell activation in normalized TME.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "medium", "disease": "Impaired antitumor immunity", "glycan_involvement": "CD80 is N-glycosylated, influencing immune interactions.", "mechanism": "CD80 upregulation marks dendritic cell maturation, promoting T cell activation.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "medium", "disease": "Immunosuppressive tumor microenvironment", "glycan_involvement": "IL-10 is glycosylated, affecting its stability and activity.", "mechanism": "IL-10 is secreted by M2 macrophages, contributing to immunosuppression; reduced by TAM repolarization.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC12138122" }, { "confidence": "high", "disease": "Immunosuppressive tumor microenvironment", "glycan_involvement": "N-glycosylation required for CD206 function and surface expression.", "mechanism": "High CD206 expression marks immunosuppressive M2 TAMs; reduction indicates repolarization to M1.", "protein": "CD206 (mannose receptor)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138122" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "Glycosylation may affect immunogenicity and ADA formation.", "mechanism": "Anti-PCSK9 mAbs (e.g., bococizumab) reduce cholesterol but can induce high-titer ADAs, reducing efficacy.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "medium", "disease": "Retinal vasculitis", "glycan_involvement": "Glycosylation may modulate immunogenicity of scFv fragments.", "mechanism": "Anti-VEGF-A scFv (brolucizumab) induces ADAs, some associated with retinal vasculitis.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Autoimmune disease", "glycan_involvement": "Fc glycosylation affects effector function and immunogenicity.", "mechanism": "Anti-TNF\u03b1 mAbs (adalimumab, golimumab) induce ADAs, reducing efficacy in autoimmune diseases.", "protein": "TNF\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Autoimmune disease", "glycan_involvement": "Fc glycosylation may reduce immunogenicity.", "mechanism": "Etanercept (TNF receptor Fc-fusion) shows low immunogenicity and limited ADA impact.", "protein": "Etanercept", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation may influence receptor binding and immunogenicity.", "mechanism": "Anti-IL-21R mAb (ATR-107) induces high ADA incidence, possibly due to target-mediated uptake.", "protein": "IL-21R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Fc glycosylation modulates ADCC/CDC and immunogenicity.", "mechanism": "Alemtuzumab (anti-CD52) induces high ADA rates in MS, reducing efficacy.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Chronic lymphocytic leukemia", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "Alemtuzumab induces low ADA rates in CLL due to immunosuppression.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation pattern affects immunogenicity and clearance.", "mechanism": "Recombinant FVIII can induce ADAs (inhibitors), reducing efficacy.", "protein": "Coagulation factor VIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Glycosylation critical for stability and immunogenicity.", "mechanism": "Recombinant EPO can induce ADAs, causing pure red cell aplasia.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Pompe disease", "glycan_involvement": "Glycosylation affects uptake and immunogenicity.", "mechanism": "Recombinant enzyme can induce ADAs, reducing efficacy and causing immune reactions.", "protein": "Acid alpha-glucosidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138202" }, { "confidence": "high", "disease": "Chemotherapy-induced cachexia", "glycan_involvement": "Hp is an N-glycoprotein; glycosylation is required for stability and secretion, but specific glycan changes not detailed.", "mechanism": "Muscle Hp expression is upregulated in response to AML chemotherapy, correlating with loss of body, lean, and muscle mass; reflects muscle atrophy and metabolic stress.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "medium", "disease": "Cancer cachexia", "glycan_involvement": "N-glycosylation required for function; no specific glycan changes described.", "mechanism": "Muscle Hp is increased in rodent and human cancer cachexia models; reflects muscle atrophy and oxidative stress.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "medium", "disease": "Sarcopenic congestive heart failure", "glycan_involvement": "Hp isoforms differ in glycosylation; glycan structure may affect function.", "mechanism": "Serum Hp phenotype correlates with skeletal muscle index and strength; Hp2 isoform negatively associated with muscle mass.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Muscle Hp can be secreted into blood; proposed as a biofluid marker for muscle wasting.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "medium", "disease": "Cancer cachexia", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Muscle Hpx is increased in cachexia; involved in haem detoxification and muscle atrophy.", "protein": "Haemopexin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "low", "disease": "Chemotherapy-induced cachexia", "glycan_involvement": "CD36 is an N-glycoprotein; glycosylation affects membrane localization.", "mechanism": "Upregulated in muscle during cachexia; involved in fatty acid metabolism.", "protein": "CD36 (Platelet glycoprotein 4)", "relationship_type": "biomarker", "source_pmcid": "PMC12138270" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Ddah1 is a glycoprotein; glycosylation may affect stability and localization.", "mechanism": "Ddah1 metabolizes ADMA, reducing its toxic accumulation and protecting renal function.", "protein": "Ddah1", "protein_enriched": { "function": "Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:31492742, PubMed", "gene_name": "Uchl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9R0P9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138378" }, { "confidence": "high", "disease": "Chronic renal injury", "glycan_involvement": "Oatp4c1 is a glycoprotein; glycosylation affects membrane trafficking.", "mechanism": "Oatp4c1 mediates renal excretion/reabsorption of ADMA and other toxins; upregulation improves clearance.", "protein": "Oatp4c1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138378" }, { "confidence": "high", "disease": "Chronic renal injury", "glycan_involvement": "Oct2 is glycosylated; glycosylation modulates transporter activity.", "mechanism": "Oct2 facilitates renal secretion of ADMA and creatinine; increased expression enhances toxin clearance.", "protein": "Oct2", "protein_enriched": { "function": "Odorant receptor", "gene_name": "OR1G1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P47890" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138378" }, { "confidence": "high", "disease": "Chronic renal injury", "glycan_involvement": "Mate1 is glycosylated; glycosylation influences transporter function.", "mechanism": "Mate1 exports ADMA and creatinine from renal cells; upregulation improves renal clearance.", "protein": "Mate1", "protein_enriched": { "function": "", "gene_name": "Zc3h7a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8R2Q7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Tubular injury", "glycan_involvement": "NAG is glycosylated; glycosylation required for enzymatic activity.", "mechanism": "Elevated NAG indicates tubular cell injury; reduction by BUP metabolites suggests protection.", "protein": "N-Acetyl-\u03b2-D-glucosidase (NAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Chronic renal injury", "glycan_involvement": "Kim-1 is heavily glycosylated; glycosylation affects detection and function.", "mechanism": "Kim-1 is upregulated in renal injury; used to monitor damage.", "protein": "Kidney injury molecule-1 (Kim-1)", "protein_enriched": { "function": "Proton-conducting pore forming subunit of the membrane integral V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells (By si", "gene_name": "VHA-c''2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SLA2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Cys-C is glycosylated; glycosylation affects stability.", "mechanism": "Cys-C levels reflect glomerular filtration rate; used for CKD diagnosis.", "protein": "Cystatin C (Cys-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "\u03b22-MG is glycosylated; glycosylation affects clearance.", "mechanism": "\u03b22-MG accumulates in CKD; used as a marker of renal dysfunction.", "protein": "\u03b22-microglobulin (\u03b22-MG)", "relationship_type": "biomarker", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect renal handling.", "mechanism": "Albuminuria is a marker of CKD progression.", "protein": "Albumin (Alb)", "relationship_type": "biomarker", "source_pmcid": "PMC12138378" }, { "confidence": "medium", "disease": "Renal dysfunction-related hypertension", "glycan_involvement": "Glycosylation regulates Oatp4c1 trafficking and function.", "mechanism": "Oatp4c1 modulation affects clearance of protein-bound toxins, impacting hypertension and cardiac hypertrophy.", "protein": "Oatp4c1", "relationship_type": "causal", "source_pmcid": "PMC12138378" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "SR-B1 is a glycoprotein; glycosylation may affect its trafficking and function.", "mechanism": "SR-B1 promotes SARS-CoV-2 infection by facilitating endolysosomal acidification required for viral entry and trafficking.", "protein": "SR-B1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "SR-B1 glycosylation may modulate receptor function.", "mechanism": "SR-B1 supports Influenza A virus infection by maintaining endolysosomal acidification necessary for viral fusion.", "protein": "SR-B1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Vesicular stomatitis", "glycan_involvement": "SR-B1 glycosylation may influence its localization and activity.", "mechanism": "SR-B1 is required for efficient VSV infection via regulation of endolysosomal pH.", "protein": "SR-B1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "SR-B1 glycosylation is important for HCV E2 binding.", "mechanism": "SR-B1 acts as an entry receptor for HCV via direct interaction with viral E2 glycoprotein.", "protein": "SR-B1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "SR-B1 glycosylation may affect NS1 binding.", "mechanism": "SR-B1 mediates DENV entry through interaction with viral NS1 protein.", "protein": "SR-B1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Spike protein is heavily glycosylated, which modulates receptor interactions.", "mechanism": "Spike protein binds cholesterol/HDL and interacts with SR-B1 to enhance viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "E2 glycosylation is critical for receptor binding and immune evasion.", "mechanism": "E2 glycoprotein binds SR-B1 to mediate viral entry.", "protein": "Hepatitis C Virus E2 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "NS1 glycosylation may influence SR-B1 interaction.", "mechanism": "NS1 interacts with SR-B1 to facilitate viral entry.", "protein": "Dengue Virus NS1", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "Hemagglutinin is glycosylated, affecting fusion and immune recognition.", "mechanism": "Hemagglutinin requires endosomal acidification (supported by SR-B1) for conformational change and fusion.", "protein": "Influenza A Virus Hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "medium", "disease": "Vesicular stomatitis", "glycan_involvement": "G protein glycosylation affects fusion efficiency.", "mechanism": "G protein-mediated fusion depends on endosomal acidification regulated by SR-B1.", "protein": "Vesicular Stomatitis Virus G protein", "relationship_type": "causal", "source_pmcid": "PMC12138404" }, { "confidence": "high", "disease": "Pregnancy-related morbidity", "glycan_involvement": "Glycosylation required for secretion and function; deficiency may relate to altered glycosylation.", "mechanism": "Protein S deficiency increases risk of fetal loss and placental complications due to impaired anticoagulant activity.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation affects plasma stability and activity.", "mechanism": "Deficiency leads to reduced inhibition of coagulation, increasing VTE risk.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Antiphospholipid Antibody Syndrome", "glycan_involvement": "Glycosylation modulates antigenicity and antibody binding.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I promote thrombosis.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation essential for secretion and anticoagulant function.", "mechanism": "Deficiency impairs inhibition of thrombin and factor Xa, increasing VTE risk.", "protein": "Antithrombin", "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Deficiency reduces inactivation of factors Va and VIIIa, promoting thrombosis.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "Glycosylation may affect protein folding and function.", "mechanism": "Factor V Leiden mutation renders factor V resistant to inactivation by activated protein C.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation influences secretion and activity.", "mechanism": "G20210A mutation increases prothrombin levels, enhancing thrombotic risk.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "medium", "disease": "Pregnancy-related morbidity", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Autoantibodies disrupt placental function, leading to fetal loss.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12138441" }, { "confidence": "medium", "disease": "Arterial Thrombosis", "glycan_involvement": "O-glycosylation regulates multimerization and function.", "mechanism": "Elevated levels associated with increased risk of arterial thrombosis.", "protein": "Von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Antiphospholipid Antibody Syndrome", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I affects antibody binding.", "mechanism": "Antibodies promote thrombosis by targeting \u03b22-glycoprotein I.", "protein": "Anticardiolipin antibodies (targeting \u03b22-glycoprotein I)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12138441" }, { "confidence": "high", "disease": "Diverticulitis", "glycan_involvement": "CRP glycosylation affects its stability and serum half-life.", "mechanism": "CRP levels rise in response to inflammation in diverticulitis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "high", "disease": "Sigmoid colon perforation", "glycan_involvement": "Glycosylation modulates CRP's immune recognition.", "mechanism": "Elevated CRP indicates acute inflammatory response to perforation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Diverticulitis", "glycan_involvement": "AGP glycosylation changes during inflammation.", "mechanism": "AGP increases during acute-phase response in diverticulitis.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation impacts transferrin's iron-binding and clearance.", "mechanism": "Altered transferrin glycosylation patterns observed in diabetes.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Altered Fc glycosylation modulates immune response.", "mechanism": "IgG glycosylation patterns change in autoimmune inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia", "glycan_involvement": "Adhesin glycosylation is essential for pathogenicity.", "mechanism": "Bacterial glycoproteins mediate host cell attachment and infection.", "protein": "Mycoplasma pneumoniae adhesins", "relationship_type": "causal", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Emphysematous pyelonephritis", "glycan_involvement": "Glycosylation affects CRP's immune signaling.", "mechanism": "CRP elevation reflects renal infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "medium", "disease": "Acute appendicitis", "glycan_involvement": "Inflammation alters AGP glycosylation.", "mechanism": "AGP rises in acute-phase response to appendicitis.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "low", "disease": "Colon cancer", "glycan_involvement": "Aberrant glycosylation may affect tumor progression.", "mechanism": "Transferrin glycosylation changes in malignancy.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "low", "disease": "Diverticulitis", "glycan_involvement": "Fc glycan changes modulate immune response.", "mechanism": "IgG glycosylation may reflect chronic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138572" }, { "confidence": "high", "disease": "COVID-19 (pediatric)", "glycan_involvement": "CRP is an N-glycosylated protein; glycosylation affects its stability and function in inflammation.", "mechanism": "CRP is elevated in response to inflammation and correlates with disease severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "high", "disease": "COVID-19 (pediatric)", "glycan_involvement": "Ferritin is glycosylated; glycosylation may modulate immune recognition.", "mechanism": "Ferritin is elevated in hyperinflammatory states and is associated with severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "high", "disease": "COVID-19 (pediatric)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects clot formation and immune interactions.", "mechanism": "Fibrinogen is increased in severe COVID-19, reflecting coagulation activation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "high", "disease": "COVID-19 (pediatric)", "glycan_involvement": "D-dimer contains glycopeptide fragments; glycosylation may influence clearance.", "mechanism": "D-dimer is a marker of fibrin degradation and is elevated in severe COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "medium", "disease": "COVID-19 (pediatric)", "glycan_involvement": "LDH is glycosylated; glycosylation may affect serum half-life.", "mechanism": "LDH is released during tissue damage and is associated with severe disease.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "medium", "disease": "COVID-19 (pediatric)", "glycan_involvement": "AST is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "AST is elevated in severe COVID-19, reflecting liver or muscle injury.", "protein": "Aspartate transaminase", "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "medium", "disease": "COVID-19 (pediatric)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "ALT is elevated in severe COVID-19, reflecting liver injury.", "protein": "Alanine transaminase", "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "high", "disease": "COVID-19 (pediatric)", "glycan_involvement": "CK is not a glycoprotein; no glycan involvement.", "mechanism": "CK is a predictor of COVID-19 severity, reflecting muscle injury.", "protein": "Creatine kinase", "relationship_type": "biomarker", "source_pmcid": "PMC12138640" }, { "confidence": "high", "disease": "Deep second-degree burn", "glycan_involvement": "N-glycosylation is required for VEGF secretion and stability.", "mechanism": "VEGF promotes angiogenesis, enhancing tissue repair and wound healing.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Deep second-degree burn", "glycan_involvement": "N-glycosylation modulates FGF receptor binding and activity.", "mechanism": "FGF stimulates fibroblast proliferation and angiogenesis, aiding wound closure.", "protein": "FGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Deep second-degree burn", "glycan_involvement": "N-glycosylation affects PDGF secretion and receptor interaction.", "mechanism": "PDGF recruits fibroblasts and promotes extracellular matrix deposition.", "protein": "PDGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138664" }, { "confidence": "high", "disease": "Deep second-degree burn", "glycan_involvement": "N-glycosylation influences TNF-\u03b1 secretion and bioactivity.", "mechanism": "Elevated TNF-\u03b1 indicates acute inflammation post-burn; reduction correlates with healing.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138664" }, { "confidence": "high", "disease": "Deep second-degree burn", "glycan_involvement": "N-glycosylation is essential for IL-6 secretion and stability.", "mechanism": "IL-6 is consistently elevated after burns and correlates with inflammation and prognosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Delayed wound healing", "glycan_involvement": "N-glycosylation required for VEGF function.", "mechanism": "Insufficient VEGF impairs angiogenesis, leading to delayed healing.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Sepsis (post-burn)", "glycan_involvement": "N-glycosylation modulates TNF-\u03b1 activity.", "mechanism": "High TNF-\u03b1 levels post-burn are associated with sepsis and poor prognosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Sepsis (post-burn)", "glycan_involvement": "N-glycosylation required for IL-6 function.", "mechanism": "Elevated IL-6 is a prognostic marker for sepsis and mortality in burn patients.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138664" }, { "confidence": "low", "disease": "Hypertrophic scar/keloid", "glycan_involvement": "N-glycosylation affects FGF signaling.", "mechanism": "bFGF promotes apoptosis in granulation tissue, preventing abnormal scar formation.", "protein": "FGF", "relationship_type": "protective", "source_pmcid": "PMC12138664" }, { "confidence": "medium", "disease": "Burn wound", "glycan_involvement": "N-glycosylation required for PDGF secretion.", "mechanism": "PDGF enhances fibroblast migration and ECM formation, supporting wound repair.", "protein": "PDGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12138664" }, { "confidence": "high", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Likely N-glycosylated; glycosylation may affect stability and localization.", "mechanism": "Overexpression promotes tumor growth, invasion, and metastasis.", "protein": "MEX3B", "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "high", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Circulates as a trimer glycoprotein; glycosylation required for secretion and function.", "mechanism": "Downregulation correlates with poor prognosis and survival.", "protein": "CTRP2 (C1QTNF2)", "protein_enriched": { "function": "", "gene_name": "KIAA2013", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q8IYS2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "high", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "C1q domain is glycosylated; glycosylation modulates activity.", "mechanism": "Dysregulation linked to tumor growth, angiogenesis, and metastasis.", "protein": "C1QTNF2", "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Predicted glycoprotein; glycosylation may regulate enzyme activity.", "mechanism": "Aberrant expression associated with metabolic reprogramming and tumor development.", "protein": "AASS", "protein_enriched": { "function": "Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), w", "gene_name": "ENOPH1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHY7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Highly glycosylated; glycosylation essential for multimerization and function.", "mechanism": "PPI network shows VWF interacts with other DEGs in UCEC.", "protein": "VWF", "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Glycosyltransferase; directly involved in O-glycan branching.", "mechanism": "Identified as prognostic biomarker; regulates glycan branching.", "protein": "GCNT1", "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Overexpression downregulates HLA-A, promoting immune evasion.", "protein": "MEX3B", "relationship_type": "causal", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may regulate enzyme stability.", "mechanism": "Overexpression or acetoacetate treatment inhibits proliferation, induces autophagy and senescence.", "protein": "AASS", "protein_enriched": { "function": "Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), w", "gene_name": "ENOPH1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHY7" }, "relationship_type": "protective", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Metabolic Disease", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Regulates lipid and carbohydrate metabolism via AMPK activation.", "protein": "CTRP2", "relationship_type": "causal", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Predicted glycoprotein; glycosylation may affect microtubule binding.", "mechanism": "Promising independent prognostic marker in early-stage UCEC.", "protein": "TPX2", "protein_enriched": { "function": "Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule", "gene_name": "TPX2", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G01678ZX", "G70316RW", "G80920RR", "G49108TO" ], "uniprot_id": "Q9ULW0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12138763" }, { "confidence": "medium", "disease": "Tricuspid Regurgitation (TR)", "glycan_involvement": "Glycoprotein composition of valve matrix affects annular compliance.", "mechanism": "Enlargement of tricuspid annulus leads to functional TR, contributing to RHF.", "protein": "Tricuspid Valve", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "medium", "disease": "Aortic Insufficiency (AI)", "glycan_involvement": "Glycoprotein-rich extracellular matrix modulates valve integrity.", "mechanism": "LVAD outflow alters valve structure, leading to AI and increased RV preload.", "protein": "Aortic Valve", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Endothelial glycoproteins regulate vascular tone and compliance.", "mechanism": "Elevated PA pressure reflects increased RV afterload and predicts RHF.", "protein": "Pulmonary Artery", "relationship_type": "biomarker", "source_pmcid": "PMC12139026" }, { "confidence": "low", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycoprotein matrix affects valve function and regurgitation severity.", "mechanism": "AI leads to worsening mitral regurgitation, increasing LV and RV volume overload.", "protein": "Mitral Valve", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "medium", "disease": "Right Heart Failure (RHF)", "glycan_involvement": "Glycoprotein-rich tissue modulates atrial compliance and strain.", "mechanism": "Impaired RA strain predicts need for RVAD and RHF development.", "protein": "Right Atrium", "relationship_type": "biomarker", "source_pmcid": "PMC12139026" }, { "confidence": "medium", "disease": "Right Heart Failure (RHF)", "glycan_involvement": "Glycoprotein structure influences myocardial elasticity and twist.", "mechanism": "Loss of LV twist and septal motion impairs RV contractility, leading to RHF.", "protein": "Left Ventricle", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "medium", "disease": "Right Heart Failure (RHF)", "glycan_involvement": "Glycoprotein matrix modulates septal compliance and contractility.", "mechanism": "Leftward shift reduces septal motion, decreasing RV contractility.", "protein": "Interventricular Septum", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "low", "disease": "Right Heart Failure (RHF)", "glycan_involvement": "Glycoprotein-rich pericardial tissue affects cardiac biomechanics.", "mechanism": "Loss of pericardial constraint reduces LV twist, impairing RV function.", "protein": "Pericardium", "relationship_type": "causal", "source_pmcid": "PMC12139026" }, { "confidence": "low", "disease": "Pulmonary Hypertension", "glycan_involvement": "Endothelial glycoproteins regulate permeability and pressure.", "mechanism": "Elevated PCWP indicates increased RV afterload and risk of RHF.", "protein": "Pulmonary Capillary", "relationship_type": "biomarker", "source_pmcid": "PMC12139026" }, { "confidence": "low", "disease": "Renal Dysfunction", "glycan_involvement": "Glycoprotein composition affects renal filtration and injury response.", "mechanism": "Renal dysfunction is a predictor of RHF after LVAD implantation.", "protein": "Renal Tissue", "relationship_type": "biomarker", "source_pmcid": "PMC12139026" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma (NPC)", "glycan_involvement": "Glycosylation of EBV envelope proteins is essential for host cell binding and immune evasion.", "mechanism": "EBV infection, mediated by viral glycoproteins, is etiologically linked to NPC pathogenesis; EBV glycoproteins facilitate viral entry and persistence in epithelial cells.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350, gp42, gH/gL complex)", "relationship_type": "causal", "source_pmcid": "PMC12139057" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma (NPC)", "glycan_involvement": "Glycosylation affects stability and immunogenicity of EBV glycoproteins, influencing circulating viral DNA levels.", "mechanism": "Plasma EBV DNA, reflecting viral glycoprotein activity and viral load, serves as a prognostic biomarker for NPC survival and recurrence risk.", "protein": "Epstein-Barr virus glycoproteins (e.g., gp350, gp42, gH/gL complex)", "relationship_type": "biomarker", "source_pmcid": "PMC12139057" }, { "confidence": "high", "disease": "Childhood obesity", "glycan_involvement": "CRP glycosylation affects its stability and inflammatory activity.", "mechanism": "CRP levels are elevated in obesity, reflecting low-grade systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139065" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates apoB function and LDL particle formation.", "mechanism": "Elevated apoB is associated with increased risk of atherosclerosis in obese children.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12139065" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences apoA-I stability and HDL function.", "mechanism": "Higher apoA-I levels are protective against CVD; often reduced in obesity.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "protective", "source_pmcid": "PMC12139065" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Insulin glycosylation affects receptor binding and clearance.", "mechanism": "Insulin resistance is a key mechanism linking obesity to T2D.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12139065" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation is essential for adiponectin multimerization and activity.", "mechanism": "Low adiponectin in obesity contributes to insulin resistance and metabolic syndrome.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12139065" }, { "confidence": "medium", "disease": "Childhood obesity", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor interaction.", "mechanism": "TNF-\u03b1 promotes inflammation and insulin resistance in obesity.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12139065" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects ferritin stability and immune recognition.", "mechanism": "Elevated ferritin reflects inflammation and altered iron metabolism in obesity.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139065" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "N-glycosylation patterns change in metabolic syndrome.", "mechanism": "Altered transferrin glycoforms are associated with metabolic disturbances in obesity.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139065" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates HDL function and anti-inflammatory properties.", "mechanism": "HDL glycoproteins contribute to reverse cholesterol transport; altered in obesity.", "protein": "HDL-associated glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12139065" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects LDL particle size and receptor binding.", "mechanism": "LDL glycoproteins promote atherogenesis; levels increased in obesity.", "protein": "LDL-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12139065" }, { "confidence": "high", "disease": "Postoperative pneumonia", "glycan_involvement": "BNP is N-glycosylated, which affects its stability and secretion.", "mechanism": "Elevated BNP reflects cardiopulmonary stress and inflammation, correlating with pneumonia severity.", "protein": "Brain natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "medium", "disease": "Severe pneumonia", "glycan_involvement": "N-glycosylation modulates BNP plasma half-life.", "mechanism": "Higher BNP levels indicate more severe pneumonia due to increased cardiac afterload and inflammation.", "protein": "Brain natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "high", "disease": "Postoperative pneumonia", "glycan_involvement": "CKMB is not glycosylated.", "mechanism": "Elevated CKMB indicates myocardial injury, which is associated with increased risk of pneumonia.", "protein": "Creatine kinase-MB (CKMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "high", "disease": "Postoperative pneumonia", "glycan_involvement": "AST is not glycosylated.", "mechanism": "Elevated AST is linked to tissue injury and inflammation, correlating with pneumonia risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "medium", "disease": "Postoperative pneumonia", "glycan_involvement": "Albumin is N-glycosylated, affecting its stability and function.", "mechanism": "Low albumin reflects poor nutritional status and impaired immunity, increasing pneumonia risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "medium", "disease": "Postoperative pneumonia", "glycan_involvement": "CRP is N-glycosylated, which modulates its immune function.", "mechanism": "CRP is an acute-phase reactant elevated in infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "low", "disease": "Hip fracture", "glycan_involvement": "N-glycosylation affects BNP secretion.", "mechanism": "BNP may be elevated in hip fracture patients due to stress and comorbid cardiac dysfunction.", "protein": "Brain natriuretic peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Not glycosylated.", "mechanism": "CKMB is a classic marker for myocardial infarction, which increases risk for pneumonia post-surgery.", "protein": "Creatine kinase-MB (CKMB)", "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects albumin function.", "mechanism": "Low albumin often co-occurs with anemia, both reflecting poor nutritional status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "medium", "disease": "Severe pneumonia", "glycan_involvement": "N-glycosylation modulates CRP's immune activity.", "mechanism": "CRP rises in severe pneumonia due to systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139096" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP glycosylation patterns may affect its detection and specificity.", "mechanism": "Elevated serum AFP is used for diagnosis and monitoring of HCC recurrence.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12139119" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Abnormal glycosylation due to vitamin K absence alters PIVKA-II structure.", "mechanism": "Elevated PIVKA-II is associated with HCC presence and recurrence risk.", "protein": "Protein induced by vitamin K absence or antagonist-II (PIVKA-II)", "protein_enriched": { "function": "Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to f", "gene_name": "F12", "glycan_count": 27, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G14994KB", "G22310AV", "G75983OB", "G84452RH", "G00912UN", "G08918WF", "G10486CT", "G45395BF", "G59626AS", "G95865ZB", "G57321FI", "G29068FM", "G53434XO", "G58001LT", "G43417UB", "G04854VP", "G06247RL", "G06356OH", "G10019LZ", "G35107SO", "G48414YA", "G57888GL", "G62461SM", "G82348BZ", "G91520UJ", "G92551JA", "G94470IW" ], "uniprot_id": "P00748" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139119" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation affects immune recognition.", "mechanism": "HBsAg positivity indicates chronic HBV infection, a major risk factor for HCC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12139119" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis may affect AFP levels.", "mechanism": "AFP may be elevated in advanced fibrosis/cirrhosis, complicating HCC diagnosis.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12139119" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation changes due to liver dysfunction impact PIVKA-II.", "mechanism": "PIVKA-II may be elevated in cirrhosis, but is more specific for HCC.", "protein": "Protein induced by vitamin K absence or antagonist-II (PIVKA-II)", "protein_enriched": { "function": "Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to f", "gene_name": "F12", "glycan_count": 27, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G14994KB", "G22310AV", "G75983OB", "G84452RH", "G00912UN", "G08918WF", "G10486CT", "G45395BF", "G59626AS", "G95865ZB", "G57321FI", "G29068FM", "G53434XO", "G58001LT", "G43417UB", "G04854VP", "G06247RL", "G06356OH", "G10019LZ", "G35107SO", "G48414YA", "G57888GL", "G62461SM", "G82348BZ", "G91520UJ", "G92551JA", "G94470IW" ], "uniprot_id": "P00748" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139119" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of HBsAg modulates immune escape and carcinogenesis.", "mechanism": "Chronic HBV infection (HBsAg+) increases risk of HCC development.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12139119" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect antigenicity and therapeutic targeting.", "mechanism": "AFP is explored as a target for immunotherapy in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139119" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation status may influence therapeutic response.", "mechanism": "PIVKA-II is considered for targeted therapy and monitoring.", "protein": "Protein induced by vitamin K absence or antagonist-II (PIVKA-II)", "protein_enriched": { "function": "Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to f", "gene_name": "F12", "glycan_count": 27, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G14994KB", "G22310AV", "G75983OB", "G84452RH", "G00912UN", "G08918WF", "G10486CT", "G45395BF", "G59626AS", "G95865ZB", "G57321FI", "G29068FM", "G53434XO", "G58001LT", "G43417UB", "G04854VP", "G06247RL", "G06356OH", "G10019LZ", "G35107SO", "G48414YA", "G57888GL", "G62461SM", "G82348BZ", "G91520UJ", "G92551JA", "G94470IW" ], "uniprot_id": "P00748" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139119" }, { "confidence": "low", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects AFP's biological activity.", "mechanism": "AFP may promote tumor growth and immune evasion in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "causal", "source_pmcid": "PMC12139119" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation of HBsAg influences chronicity and fibrogenesis.", "mechanism": "Chronic HBV infection (HBsAg+) leads to liver fibrosis and cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12139119" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates receptor stability and cell surface expression.", "mechanism": "GPCRs are drug targets for cancer therapy; their glycosylation affects ligand binding and signaling.", "protein": "GPCRs", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Fc N-glycosylation regulates antibody-dependent cellular cytotoxicity.", "mechanism": "IgG glycosylation status influences immune effector functions and disease progression.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "N-glycosylation at multiple sites required for serum half-life and receptor binding.", "mechanism": "EPO stimulates erythropoiesis; glycosylation is essential for stability and activity.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates ligand binding and dimerization.", "mechanism": "EGFR is overexpressed in tumors; glycosylation affects receptor activation and drug response.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Disulfide bond formation and glycosylation in ER-derived vesicles enhance stability.", "mechanism": "scFvs are used for targeted cancer therapy; glycosylation impacts folding and antigen binding.", "protein": "scFv", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects trafficking and membrane localization.", "mechanism": "Connexin 43 glycosylation regulates gap junction formation and cardiac conduction.", "protein": "Connexin 43", "relationship_type": "biomarker", "source_pmcid": "PMC12139124" }, { "confidence": "medium", "disease": "Drug-resistant infections", "glycan_involvement": "Glycosylation modulates protein folding and stability.", "mechanism": "Porin F is a target for antibiotics; glycosylation influences membrane permeability.", "protein": "Outer membrane porin F", "protein_enriched": { "function": "Resistance to tetracycline by an active tetracycline efflux. This is an energy-dependent process that decreases the accumulation of the antibiotic in whole cells. This protein functions as a metal-tet", "gene_name": "tetA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02981" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation enhances stability and reduces immunogenicity.", "mechanism": "\u03b1HER2 affibody binds HER2 in breast cancer; glycosylation affects binding affinity.", "protein": "\u03b1HER2 affibody", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "low", "disease": "Neurological disorders", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Used in optogenetics for neurological disease models; glycosylation affects membrane integration.", "protein": "Bacteriorhodopsin", "protein_enriched": { "function": "Light-driven proton pump", "gene_name": "bop", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02945" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139124" }, { "confidence": "low", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation modulates membrane localization and activity.", "mechanism": "NarX-L detects nitrate as a marker of inflammation; glycosylation affects sensor function.", "protein": "NarX-L", "relationship_type": "biomarker", "source_pmcid": "PMC12139124" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation may affect CBH stability and activity.", "mechanism": "CBH deconjugates bile acids, reducing blood cholesterol and modulating lipid metabolism.", "protein": "Choloylglycine hydrolase (CBH)", "relationship_type": "protective", "source_pmcid": "PMC12139142" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation may regulate ATPase assembly and function.", "mechanism": "Enhanced ATP synthesis in gut microbiota increases host energy harvest and weight gain.", "protein": "F-type ATPase", "relationship_type": "causal", "source_pmcid": "PMC12139142" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Increased glycolytic flux in microbiota correlates with altered host metabolism.", "protein": "Phosphoglycerate kinase", "relationship_type": "biomarker", "source_pmcid": "PMC12139142" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Upregulated TCA cycle enzymes in microbiota may influence host glucose homeostasis.", "protein": "Succinyl-CoA synthetase", "relationship_type": "causal", "source_pmcid": "PMC12139142" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation may impact secretion and activity.", "mechanism": "Microbial lipase activity increases lipid absorption and serum triglycerides.", "protein": "Triacylglycerol lipase", "relationship_type": "causal", "source_pmcid": "PMC12139142" }, { "confidence": "medium", "disease": "Liver mitochondrial stress", "glycan_involvement": "Glycosylation may regulate enzyme turnover.", "mechanism": "Enhanced beta-oxidation in microbiota increases host mitochondrial load.", "protein": "Acyl-CoA dehydrogenase", "relationship_type": "causal", "source_pmcid": "PMC12139142" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation may affect butyrate kinase activity.", "mechanism": "Microbial butyrate production supports gut barrier and anti-inflammatory effects.", "protein": "Butyrate kinase", "relationship_type": "protective", "source_pmcid": "PMC12139142" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Altered glycosylation may affect albumin function.", "mechanism": "Serum albumin levels reflect metabolic and cardiovascular risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139142" }, { "confidence": "low", "disease": "Digestive disorders", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Microbial acetate production supports gut health.", "protein": "Acetate kinase", "relationship_type": "protective", "source_pmcid": "PMC12139142" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may regulate enzyme function.", "mechanism": "Altered microbial pyruvate metabolism may influence host cancer risk.", "protein": "Pyruvate kinase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139142" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; its glycosylation status can affect detection sensitivity and specificity.", "mechanism": "AFP is elevated in the serum of patients with HCC and is used for diagnosis and monitoring.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139162" }, { "confidence": "high", "disease": "Bovine tuberculosis", "glycan_involvement": "Glycosylation required for BCR surface expression and function.", "mechanism": "Marks B cell-rich follicle-like structures in granulomas, indicating TLS formation.", "protein": "CD79A", "protein_enriched": { "function": "Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk", "gene_name": "CSN3", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "P02670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "high", "disease": "Bovine tuberculosis", "glycan_involvement": "Glycosylation affects TCR assembly and signaling.", "mechanism": "Identifies T cell zones in granulomas; peripheral localization may limit direct pathogen interaction.", "protein": "CD3\u03b5", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "high", "disease": "Pulmonary granuloma", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell adhesion and migration.", "mechanism": "Marks endothelial cells and HEVs surrounding TLSs, facilitating lymphocyte trafficking.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Bovine tuberculosis", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Expressed by T follicular helper cells in TLSs; critical for germinal center formation and B cell help.", "protein": "ICOS (CD278)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139164" }, { "confidence": "high", "disease": "Pulmonary granuloma", "glycan_involvement": "Glycosylation influences chemokine stability and receptor binding.", "mechanism": "Chemokine driving B cell recruitment and TLS formation in granulomas.", "protein": "CXCL13", "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Pulmonary granuloma", "glycan_involvement": "Glycosylation affects chemokine gradient formation.", "mechanism": "Chemokine organizing T cell zones in TLSs; supports compartmentalization.", "protein": "CCL19", "protein_enriched": { "function": "May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell ", "gene_name": "CCL19", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99731" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Pulmonary granuloma", "glycan_involvement": "Glycosylation modulates interaction with CCR7 receptor.", "mechanism": "Chemokine mediating lymphocyte extravasation and TLS maintenance.", "protein": "CCL21", "protein_enriched": { "function": "Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T", "gene_name": "CCL21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00585" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Bovine tuberculosis", "glycan_involvement": "N-glycosylation regulates integrin activation and adhesion.", "mechanism": "Identifies myeloid cells in granulomas; involved in immune cell recruitment.", "protein": "CD11b (ITGAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Bovine tuberculosis", "glycan_involvement": "N-glycosylation modulates integrin function.", "mechanism": "Marks dendritic cells in granulomas; supports antigen presentation.", "protein": "CD11c (ITGAX)", "relationship_type": "biomarker", "source_pmcid": "PMC12139164" }, { "confidence": "medium", "disease": "Pulmonary granuloma", "glycan_involvement": "Glycosylation of both L-selectin and its ligands is essential for binding and trafficking.", "mechanism": "Facilitates lymphocyte homing to TLSs via interaction with glycosylated ligands on HEVs.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139164" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "sTfR is N-glycosylated, which affects its stability and serum levels.", "mechanism": "Elevated sTfR indicates increased cellular iron demand and iron deficiency.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12139176" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "Ferritin is glycosylated, influencing its serum half-life and detection.", "mechanism": "Low ferritin reflects depleted iron stores.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Respiratory infectious illness", "glycan_involvement": "CRP glycosylation modulates its immune recognition and clearance.", "mechanism": "Elevated CRP is associated with inflammation and increased risk of respiratory illness.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Respiratory infectious illness", "glycan_involvement": "N-glycosylation affects sTfR serum levels and immune interactions.", "mechanism": "Iron sufficient erythropoiesis (low sTfR) at early pregnancy is associated with increased risk of respiratory infectious illness during iron supplementation.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Gastric infectious illness", "glycan_involvement": "Glycosylation impacts ferritin stability and immune signaling.", "mechanism": "Low ferritin (iron deficiency) increases odds of gastric infectious illness.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "high", "disease": "Anaemia", "glycan_involvement": "Minor glycosylation, not central to function.", "mechanism": "Low Hb is diagnostic for anaemia.", "protein": "Hemoglobin (Hb)", "relationship_type": "biomarker", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Respiratory infectious illness", "glycan_involvement": "Not significant for mechanism.", "mechanism": "Anaemic women have longer duration of respiratory illness.", "protein": "Hemoglobin (Hb)", "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Vomiting", "glycan_involvement": "Not significant for mechanism.", "mechanism": "Anaemic women experience more incidences of vomiting during pregnancy.", "protein": "Hemoglobin (Hb)", "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Diarrhoea", "glycan_involvement": "Not significant for mechanism.", "mechanism": "Anaemic women experience more incidences of diarrhoea.", "protein": "Hemoglobin (Hb)", "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "medium", "disease": "Respiratory infectious illness", "glycan_involvement": "CRP glycosylation modulates immune response.", "mechanism": "Higher baseline CRP is associated with increased risk of respiratory illness.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "causal", "source_pmcid": "PMC12139176" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "MGMT is a glycoprotein; glycosylation not directly discussed but may affect stability.", "mechanism": "MGMT repairs O6-methylguanine DNA lesions, conferring resistance to temozolomide; promoter methylation reduces MGMT expression and increases TMZ sensitivity.", "protein": "MGMT", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12139195" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation by GLT8D1 stabilizes CD133, enhancing Wnt/\u03b2-catenin signaling and tumorigenesis.", "mechanism": "CD133 marks glioma stem cells (GSCs) with high resistance to TMZ; glycosylation stabilizes CD133 and promotes stemness.", "protein": "CD133", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12139195" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Directly mediates glycosylation of CD133.", "mechanism": "GLT8D1 glycosylates CD133 under hypoxia, promoting GSC stemness and TMZ resistance.", "protein": "GLT8D1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139195" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "MRP-1 is a glycoprotein; glycosylation may affect trafficking and function.", "mechanism": "MRP-1 is upregulated via Wnt/\u03b2-catenin signaling in endothelial cells, promoting drug efflux and TMZ resistance.", "protein": "MRP-1 (ABCC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139195" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "LAMP2A is a lysosomal glycoprotein; glycosylation required for stability and function.", "mechanism": "LAMP2A mediates chaperone-mediated autophagy, sustaining GSC stemness and TMZ resistance; high levels correlate with poor survival.", "protein": "LAMP2A", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12139195" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "MAN1A1 is a mannosidase involved in N-glycan processing; deficiency alters glycoprotein interactions.", "mechanism": "MAN1A1 deficiency in GSCs promotes CD133-DNMT1 interaction, maintaining quiescence and TMZ resistance.", "protein": "MAN1A1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139195" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "ITGA1 is a glycoprotein; glycosylation affects cell adhesion and signaling.", "mechanism": "Upregulated by circRNAs, ITGA1 promotes cell proliferation and TMZ resistance via PI3K/AKT pathway activation.", "protein": "ITGA1", "protein_enriched": { "function": "Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake (PubMed:10829012, PubMed:3", "gene_name": "GFRA1", "glycan_count": 14, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G57321FI", "G02628JF", "G08110WX", "G11911BT", "G45395BF", "G46524LG", "G56284ZY", "G62765YT", "G70232NH", "G81198YO", "G82592ZH", "G99966GV", "G49108TO" ], "uniprot_id": "P56159" }, "relationship_type": "causal", "source_pmcid": "PMC12139195" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "No direct glycosylation discussed.", "mechanism": "USP36 stabilizes ALKBH5, sustaining GSC self-renewal and TMZ resistance.", "protein": "USP36", "protein_enriched": { "function": "Translation initiation regulator which represses non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation ", "gene_name": "BZW2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6E2" }, "relationship_type": "causal", "source_pmcid": "PMC12139195" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "No direct glycosylation discussed.", "mechanism": "Stabilized by USP36, ALKBH5 maintains GSC stemness and TMZ resistance.", "protein": "ALKBH5", "protein_enriched": { "function": "Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubM", "gene_name": "ALKBH5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6P6C2" }, "relationship_type": "causal", "source_pmcid": "PMC12139195" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "CAV1 is a glycoprotein; glycosylation may affect membrane localization.", "mechanism": "CAV1 interacts with TRAF4 to activate survival signaling, contributing to TMZ resistance.", "protein": "CAV1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139195" }, { "confidence": "high", "disease": "Biliary Atresia (BA)", "glycan_involvement": "Glycosylation affects MMP7 secretion and stability.", "mechanism": "Elevated serum MMP7 is associated with BA diagnosis and earlier detection.", "protein": "Matrix Metalloproteinase 7 (MMP7)", "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "high", "disease": "Biliary Atresia (BA)", "glycan_involvement": "Glycosylation required for \u03b3-GGT membrane localization and activity.", "mechanism": "Elevated \u03b3-GGT is indicative of cholestasis and BA.", "protein": "Gamma-glutamyl transpeptidase (\u03b3-GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Biliary Atresia (BA)", "glycan_involvement": "Glycosylation modulates ALP stability and function.", "mechanism": "ALP elevation reflects bile duct injury and cholestasis in BA.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences AST serum half-life.", "mechanism": "Elevated AST is a marker of hepatocellular injury and fibrosis progression.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects ALT secretion.", "mechanism": "ALT elevation signals liver cell damage and fibrosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "high", "disease": "Cholangitis", "glycan_involvement": "Glycosylation essential for CRP function and immune recognition.", "mechanism": "CRP elevation is used to detect inflammation in cholangitis post-KPE.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates MMP7 activity and tissue distribution.", "mechanism": "MMP7 promotes extracellular matrix remodeling and fibrosis in BA.", "protein": "Matrix Metalloproteinase 7 (MMP7)", "relationship_type": "causal", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation required for \u03b3-GGT enzymatic activity.", "mechanism": "Persistent \u03b3-GGT elevation correlates with progression to cirrhosis in BA.", "protein": "Gamma-glutamyl transpeptidase (\u03b3-GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation affects MMP7 serum levels.", "mechanism": "High MMP7 levels may predict risk of portal hypertension in BA.", "protein": "Matrix Metalloproteinase 7 (MMP7)", "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for CRP stability and function.", "mechanism": "CRP elevation reflects ongoing inflammation contributing to fibrosis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139268" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "UFM1 is a ubiquitin-like modifier; not a classical glycan, but modifies lysine residues on glycoproteins.", "mechanism": "UFM1 levels and conjugation are increased in AD cortex, correlating with pathological tau aggregation and spreading.", "protein": "UFM1", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBT9" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "ER-resident glycoprotein, modified by UFM1.", "mechanism": "DDRGK1 is required for UFMylation at the ER; its reduction impairs ER stress response and increases cell death, relevant to AD pathology.", "protein": "DDRGK1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "E3 ligase for UFMylation of glycoproteins.", "mechanism": "UFL1 ligase activity regulates UFMylation of DDR proteins (MRE11, p53, PARP1) and ER stress sensors, impacting tau aggregation and neurodegeneration.", "protein": "UFL1", "protein_enriched": { "function": "Core component of a Cul9-RING ubiquitin-protein ligase complex composed of CUL9 and RBX1 (PubMed:38605244). The CUL9-RBX1 complex mediates ubiquitination and subsequent degradation of BIRC5 and is req", "gene_name": "CUL9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q8IWT3" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139329" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "ER-associated glycoprotein, UFMylated at Lys610.", "mechanism": "HRD1 UFMylation enhances degradation of misfolded proteins (APP, tau); HRD1 deficiency leads to APP and tau accumulation in AD.", "protein": "HRD1 (SYVN1)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubM", "gene_name": "SYVN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86TM6" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycoprotein, UFMylated at Lys69/114/130.", "mechanism": "UFMylation stabilizes P4HB, preventing ER stress; loss of UFMylation leads to degradation and increased oxidative/ER stress, contributing to AD.", "protein": "P4HB", "relationship_type": "protective", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "ER glycoprotein, UFMylated.", "mechanism": "UFMylation of RPN1 facilitates ER-phagy; RPN1 is elevated in AD brain capillaries, suggesting dysregulated ER-phagy.", "protein": "RPN1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Ribosomal glycoprotein, UFMylated.", "mechanism": "UFMylation of RPL26 is required for ER-phagy; RPL26 immunoreactivity is reduced in AD neurons, proposed as AD biomarker.", "protein": "RPL26", "protein_enriched": { "function": "Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs", "gene_name": "RPL27", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61353" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "ER membrane glycoprotein, UFMylated.", "mechanism": "UFMylation inactivates CYB5R3, inducing ER-phagy; CYB5R3 levels are reduced in AD mouse CSF, suggesting ER-phagy dysfunction.", "protein": "CYB5R3", "protein_enriched": { "function": "Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor", "gene_name": "CYB5R3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ", "G49108TO" ], "uniprot_id": "P00387" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Autophagy-related glycoprotein, UFMylated.", "mechanism": "UFMylation maintains Atg9A levels for autophagy; Atg9A accumulates in dystrophic neurites in AD models.", "protein": "Atg9A", "protein_enriched": { "function": "Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922, PubMed:29437695, PubMed:32513819, PubMed:32610138, PubMed:33106659, PubM", "gene_name": "ATG9A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q7Z3C6" }, "relationship_type": "causal", "source_pmcid": "PMC12139329" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "AAA ATPase glycoprotein, UFMylated at K109.", "mechanism": "UFMylation of VCP/p97 enhances BECN1 stabilization and autophagy initiation; VCP mediates tau disaggregation.", "protein": "VCP/p97", "relationship_type": "protective", "source_pmcid": "PMC12139329" }, { "confidence": "high", "disease": "Anti-inflammatory", "glycan_involvement": "Glycosylation essential for bioactivity and solubility", "mechanism": "Suppresses inflammatory mediators", "protein": "Paeoniflorin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139386" }, { "confidence": "high", "disease": "Analgesic", "glycan_involvement": "Glycoside moiety required for receptor interaction", "mechanism": "Modulates pain signaling pathways", "protein": "Paeoniflorin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Antidepressant", "glycan_involvement": "Glycosylation increases CNS bioavailability", "mechanism": "Regulates neurotransmitter levels", "protein": "Albiflorin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Antioxidant", "glycan_involvement": "Glycosylation enhances radical scavenging", "mechanism": "Scavenges free radicals", "protein": "Oxypaeoniflorin", "relationship_type": "protective", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Anti-liver fibrosis", "glycan_involvement": "Glycosylation required for hepatic uptake", "mechanism": "Inhibits hepatic stellate cell activation", "protein": "Benzoylpaeoniflorin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Anti-tumor", "glycan_involvement": "Glycoside structure critical for cell entry", "mechanism": "Induces apoptosis in tumor cells", "protein": "Procyanidin B2", "relationship_type": "protective", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Antibacterial", "glycan_involvement": "Glycosylation facilitates membrane interaction", "mechanism": "Disrupts bacterial cell wall synthesis", "protein": "Cinnamtannin A2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Protective against oxidative damage", "glycan_involvement": "Glycosylation increases antioxidant potency", "mechanism": "Reduces oxidative stress in tissues", "protein": "Catechin", "relationship_type": "protective", "source_pmcid": "PMC12139386" }, { "confidence": "high", "disease": "Anti-inflammatory", "glycan_involvement": "Directly mediates glycosylation of bioactive compounds", "mechanism": "Catalyzes glycosylation of MGs, enabling anti-inflammatory activity", "protein": "UGT91A1.1", "relationship_type": "causal", "source_pmcid": "PMC12139386" }, { "confidence": "high", "disease": "Anti-tumor", "glycan_involvement": "Glycosylation required for flavonoid bioactivity", "mechanism": "Glycosylates flavonoids, enhancing anti-tumor effects", "protein": "UGT89B2", "relationship_type": "causal", "source_pmcid": "PMC12139386" }, { "confidence": "medium", "disease": "Liver injury (LI)", "glycan_involvement": "IL-6R glycosylation affects receptor function and drug binding.", "mechanism": "Use of IL-6R inhibitors (tocilizumab, sarilumab) is associated with increased risk of LI in COVID-19 patients.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "Liver injury (LI)", "glycan_involvement": "CD19 is a heavily glycosylated B-cell marker; glycosylation modulates immune signaling.", "mechanism": "Higher CD19+ B cell counts are associated with LI, indicating immune activation.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "high", "disease": "Liver injury (LI)", "glycan_involvement": "GGT is glycosylated, affecting stability and membrane localization.", "mechanism": "Elevated GGT at admission independently predicts LI in COVID-19 patients.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "high", "disease": "Liver injury (LI)", "glycan_involvement": "Minor glycosylation; not central to mechanism.", "mechanism": "ALT >3x ULN defines LI; elevated in both early and late LI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "high", "disease": "Liver injury (LI)", "glycan_involvement": "Minor glycosylation; not central to mechanism.", "mechanism": "AST >3x ULN defines LI; elevated in both early and late LI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Glycosylation modulates IL-6R function and drug response.", "mechanism": "IL-6R inhibitors are used in severe COVID-19, but may increase risk of LI.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD3 glycosylation affects T-cell receptor signaling.", "mechanism": "Profound lymphopenia (decreased CD3+ T cells) observed in severe COVID-19, regardless of LI.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD4 glycosylation modulates immune interactions.", "mechanism": "Decreased CD4+ T cells in severe COVID-19, not directly linked to LI.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD8 glycosylation modulates cytotoxic function.", "mechanism": "Decreased CD8+ T cells in severe COVID-19, not directly linked to LI.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "high", "disease": "In-hospital mortality", "glycan_involvement": "Glycosylation affects GGT activity and stability.", "mechanism": "Elevated GGT and late LI independently predict in-hospital death in COVID-19.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139466" }, { "confidence": "medium", "disease": "Pericardial effusion", "glycan_involvement": "CRP glycosylation affects its stability and clearance.", "mechanism": "CRP is elevated in inflammatory and infectious causes of pericardial effusion.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "medium", "disease": "Pericardial effusion", "glycan_involvement": "Albumin glycosylation can affect its half-life and function.", "mechanism": "Serum albumin levels are monitored to assess liver function and fluid status in pericardial effusion.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Hepatic dysfunction", "glycan_involvement": "Glycosylation may modulate enzyme stability.", "mechanism": "Elevated AST indicates hepatic congestion due to cardiac tamponade.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Hepatic dysfunction", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "ALT elevation reflects hepatic congestion in tamponade.", "protein": "Alanine transaminase", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Renal dysfunction", "glycan_involvement": "Altered glycosylation may affect renal clearance.", "mechanism": "Serum albumin is used to monitor renal function and fluid overload.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Tuberculous pericardial effusion", "glycan_involvement": "Glycosylation modulates CRP's immune function.", "mechanism": "CRP is elevated in TB pericarditis, reflecting inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Malignancy-associated pericardial effusion", "glycan_involvement": "Glycosylation affects CRP's interaction with immune cells.", "mechanism": "CRP may be elevated in malignancy-related effusions due to inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Malignancy-associated pericardial effusion", "glycan_involvement": "Altered glycosylation may reflect disease state.", "mechanism": "Hypoalbuminemia may be present in malignancy-related effusions.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Hepatic dysfunction", "glycan_involvement": "Albumin glycosylation may affect bilirubin binding.", "mechanism": "Elevated bilirubin indicates hepatic congestion in tamponade.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "low", "disease": "Viral pericardial effusion", "glycan_involvement": "Glycosylation modulates CRP's immune recognition.", "mechanism": "CRP is elevated in viral pericarditis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12139644" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Collagen IV is a glycoprotein; its deposition is a hallmark of DKD.", "mechanism": "Excessive accumulation in renal mesangial cells leads to glomerulosclerosis and fibrosis.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12139686" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Fibronectin is a glycoprotein; its glycosylation is important for ECM structure.", "mechanism": "Overproduction and deposition in ECM contributes to renal fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12139686" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "Induces ECM protein synthesis and fibrosis via SMAD3 signaling.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139686" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "No direct glycosylation, but regulates glycoprotein expression.", "mechanism": "Mediator of TGF-\u03b21 signaling; promotes ECM accumulation and fibrosis.", "protein": "SMAD3", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84022" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12139686" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Indirect; regulates expression of ECM glycoproteins.", "mechanism": "Upregulated in DKD; regulates ECM glycoprotein accumulation via miR-136-5p/SMAD3 axis.", "protein": "circ_0054633", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12139686" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Indirect; affects glycoprotein expression.", "mechanism": "Serum levels elevated in DM and DKD; correlates with disease progression.", "protein": "circ_0054633", "relationship_type": "biomarker", "source_pmcid": "PMC12139686" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation affects ECM structure and function.", "mechanism": "Increased ECM protein in early diabetic nephropathy.", "protein": "Collagen IV", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12139686" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation modulates ECM interactions.", "mechanism": "Elevated in renal tissue in DM; precedes DKD.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139686" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Serum levels correlate with circ_0054633 and disease severity.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139686" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Indirect; regulates glycoprotein gene expression.", "mechanism": "Upregulated in hyperglycemic conditions; mediates early ECM changes.", "protein": "SMAD3", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12139686" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns (e.g., AFP-L3) enhance specificity for HCC.", "mechanism": "Elevated serum AFP indicates tumor burden and progression in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects stability and detection in serum.", "mechanism": "Elevated DCP/APT reflects abnormal vitamin K-dependent carboxylation in HCC.", "protein": "Abnormal prothrombin (Des-gamma-carboxy prothrombin)", "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates secretion and function.", "mechanism": "Prolonged prothrombin time (PT) is associated with poor prognosis and resistance to HAIC.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation influences enzyme activity and serum levels.", "mechanism": "Elevated AKP indicates increased tumor burden and predicts HAIC response.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation modulates CRP's immunological activity.", "mechanism": "High CRP reflects systemic inflammation and correlates with resistance to HAIC.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation status can affect half-life and function.", "mechanism": "Low albumin indicates impaired liver synthetic function in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects membrane localization and activity.", "mechanism": "Elevated GGT is associated with tumor progression and poor prognosis.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "N-glycosylation critical for viral infectivity and immune evasion.", "mechanism": "HBsAg presence indicates active HBV infection, a major risk factor for HCC.", "protein": "Hepatitis B surface antigen", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03138" }, "relationship_type": "causal", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatitis B virus infection", "glycan_involvement": "Glycosylation modulates secretion and immune recognition.", "mechanism": "HBeAg positivity indicates active viral replication, increasing HCC risk.", "protein": "Hepatitis B e antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "medium", "disease": "Hepatitis B virus infection", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "HBcAg positivity reflects ongoing HBV infection and immune response.", "protein": "Hepatitis B core antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12140075" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "N-glycosylation affects antigenicity and immune recognition.", "mechanism": "HBsAg is used to diagnose and monitor HBV infection and treatment response.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12140211" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "N-glycosylation modulates secretion and immune evasion.", "mechanism": "HBeAg positivity indicates active viral replication and infectivity.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140211" }, { "confidence": "medium", "disease": "Drug resistance", "glycan_involvement": "Indirect; glycosylation may affect polymerase stability.", "mechanism": "Mutations in HBV polymerase can confer resistance to TAF.", "protein": "Hepatitis B virus DNA polymerase", "relationship_type": "causal", "source_pmcid": "PMC12140211" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation affects enzyme stability and serum levels.", "mechanism": "Elevated ALT signals liver injury or steatosis during TAF therapy.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140211" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Elevated AST is associated with liver injury and risk of HCC.", "protein": "Transaminases (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12140211" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects enzyme release and detection.", "mechanism": "Elevated CK-MB may reflect muscle/bone injury during TAF therapy.", "protein": "Creatine kinase MB", "relationship_type": "biomarker", "source_pmcid": "PMC12140211" }, { "confidence": "medium", "disease": "Cerebral infarction", "glycan_involvement": "Glycosylation influences LDL receptor binding and clearance.", "mechanism": "TAF increases LDL, promoting atherosclerosis and risk of stroke.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12140211" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates LDL metabolism and neuronal uptake.", "mechanism": "Elevated LDL may promote \u03b2-amyloid deposition and dementia risk.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12140211" }, { "confidence": "medium", "disease": "Hypophosphatemia", "glycan_involvement": "Glycosylation affects transporter localization and function.", "mechanism": "TAF-induced renal tubular dysfunction impairs phosphate reabsorption.", "protein": "Phosphorus transporters (general)", "relationship_type": "causal", "source_pmcid": "PMC12140211" }, { "confidence": "low", "disease": "Dementia", "glycan_involvement": "N-glycosylation regulates APP cleavage and aggregation.", "mechanism": "TAF-associated dyslipidemia may enhance APP processing and amyloid deposition.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12140211" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP reflects systemic inflammation, which contributes to CVD onset and progression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Surface glycosylation modulates neutrophil-endothelial interactions.", "mechanism": "Neutrophil count (and surface glycoproteins) indicate acute inflammation linked to CVD risk.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects monocyte migration and adhesion.", "mechanism": "Monocyte count is associated with CVD progression via inflammation.", "protein": "Monocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "All-cause mortality", "glycan_involvement": "Glycosylation regulates lymphocyte trafficking and survival.", "mechanism": "Low lymphocyte count predicts higher all-cause mortality; reflects immune status.", "protein": "Lymphocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "high", "disease": "All-cause mortality", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is associated with increased risk of death from any cause.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation influences neutrophil-tumor interactions.", "mechanism": "High neutrophil count (and dNLR) predicts poor cancer prognosis.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects CRP's immune recognition.", "mechanism": "CRP elevation reflects tumor-associated inflammation and poor prognosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates neutrophil activation in infection.", "mechanism": "High dNLR predicts mortality in COVID-19, reflecting immune dysregulation.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "All-cause mortality", "glycan_involvement": "Albumin glycosylation status can affect its half-life and function.", "mechanism": "Low albumin is associated with increased mortality risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "medium", "disease": "Acute coronary syndrome", "glycan_involvement": "Glycosylation affects neutrophil-endothelial adhesion in ACS.", "mechanism": "High dNLR predicts mortality in acute coronary syndrome.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140284" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Elevated CRP reflects persistent systemic inflammation, associated with increased cardiovascular risk post-TB.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "IL-6 is glycosylated, which modulates receptor binding and signaling.", "mechanism": "Chronic elevation of IL-6 is linked to increased cancer risk in TB survivors.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Post-TB lung disease", "glycan_involvement": "Glycosylation critical for inhibitor activity and stability.", "mechanism": "Lower levels inversely correlate with lung function (FEV1) post-TB.", "protein": "Alpha-1 protease inhibitor (SERPINA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Fibrotic lung damage", "glycan_involvement": "Glycosylation modulates secretion and receptor interaction.", "mechanism": "Elevated TGF-\u03b2 promotes fibrosis and scarring in post-TB lungs.", "protein": "Transforming growth factor beta (TGF-\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Tuberculosis relapse", "glycan_involvement": "Glycosylation affects cytokine stability and activity.", "mechanism": "Combined with other markers, IL-1\u03b2 predicts relapse risk.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Tuberculosis relapse", "glycan_involvement": "Glycosylation influences chemokine gradient formation.", "mechanism": "Elevated CXCL10, with other markers, improves relapse prediction.", "protein": "CXCL10 (IP-10)", "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Tuberculosis relapse", "glycan_involvement": "Glycosylation required for LPS binding and immune activation.", "mechanism": "High LBP levels indicate increased risk of relapse via intestinal translocation.", "protein": "LPS-binding protein (LBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Tuberculosis relapse", "glycan_involvement": "Glycosylation affects receptor shedding and signaling.", "mechanism": "Combined with other markers, sIL-6R improves relapse risk stratification.", "protein": "Soluble IL-6 receptor (sIL-6R)", "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Tuberculosis relapse", "glycan_involvement": "Glycosylation essential for complement activation.", "mechanism": "C3 levels, with other markers, predict relapse risk.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "medium", "disease": "Paradoxical reaction/IRIS", "glycan_involvement": "Glycosylation modulates TNF receptor binding.", "mechanism": "Elevated TNF associated with excessive inflammation and IRIS.", "protein": "Tumor necrosis factor (TNF)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "Tnf", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P06804" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140437" }, { "confidence": "high", "disease": "Iron Overload", "glycan_involvement": "Ferritin is a glycoprotein; glycosylation may affect its stability and serum half-life.", "mechanism": "Serum ferritin levels reflect total body iron stores; elevated in transfusion-dependent thalassemia due to iron accumulation.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12140608" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "Glycosylation may influence ferritin's clearance and detection in serum.", "mechanism": "High serum ferritin correlates with elevated ALT/AST, indicating hepatic iron overload and liver injury.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12140608" }, { "confidence": "high", "disease": "Thalassemia (\u03b1- and \u03b2-thalassemia)", "glycan_involvement": "Hemoglobin is a glycoprotein; glycosylation status not directly discussed in this article.", "mechanism": "Mutations in \u03b1- or \u03b2-globin genes reduce Hb synthesis, causing anemia.", "protein": "Hemoglobin (Hb)", "relationship_type": "causal", "source_pmcid": "PMC12140608" }, { "confidence": "medium", "disease": "Hepatomegaly", "glycan_involvement": "Glycosylation may affect ferritin's serum levels.", "mechanism": "Elevated ferritin indicates iron overload, which contributes to liver enlargement.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12140608" }, { "confidence": "medium", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation may affect ferritin's serum levels.", "mechanism": "Iron overload (high ferritin) is associated with splenic enlargement in thalassemia.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12140608" }, { "confidence": "high", "disease": "Thalassemia (\u03b1- and \u03b2-thalassemia)", "glycan_involvement": "Ferritin glycosylation may influence its diagnostic accuracy.", "mechanism": "Used to monitor iron overload in transfusion-dependent thalassemia patients.", "protein": "Serum Ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12140608" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Transducin is glycosylated; glycan structures may influence antigenicity and immune recognition.", "mechanism": "Autoantibodies against transducin are detected in MAR, indicating immune-mediated retinal dysfunction.", "protein": "Transducin", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may affect antigen presentation and immune response.", "mechanism": "Circulating autoantibodies against aldolase C are found in MAR, contributing to retinal cell dysfunction.", "protein": "Aldolase C", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies against aldolase A are present in MAR, associated with retinal damage.", "protein": "Aldolase A", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Autoantibodies against mitogen-activated protein detected in MAR, linked to retinal dysfunction.", "protein": "Mitogen-activated protein", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may affect immune response.", "mechanism": "Autoantibodies against titin found in MAR, contributing to immune-mediated retinal injury.", "protein": "Titin", "protein_enriched": { "function": "Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between t", "gene_name": "TTN", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G57321FI" ], "uniprot_id": "Q8WZ42" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may modulate antigenicity and immune targeting.", "mechanism": "Autoantibodies against M\u00fcller cell proteins are associated with MAR and retinal dysfunction.", "protein": "M\u00fcller glial cell proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "medium", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "Autoantibodies against neuronal antigens are detected in MAR, indicating immune-mediated retinal damage.", "protein": "Neuronal antigens", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "low", "disease": "Diabetic retinopathy", "glycan_involvement": "Altered glycosylation may contribute to immune recognition.", "mechanism": "Autoantibodies against retinal glycoproteins are also found in diabetic retinopathy, suggesting shared immune mechanisms.", "protein": "Retinal glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "low", "disease": "Retinal vasculitis", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against retinal glycoproteins are present in retinal vasculitis, indicating immune involvement.", "protein": "Retinal glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12140611" }, { "confidence": "high", "disease": "Melanoma-associated retinopathy (MAR)", "glycan_involvement": "Glycosylation of bipolar cell proteins may be critical for antibody binding and immune-mediated cell death.", "mechanism": "Autoantibodies cross-react with glycoproteins on retinal bipolar cells, inducing apoptosis and visual dysfunction.", "protein": "Retinal bipolar cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12140611" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects stability and detection in serum assays.", "mechanism": "Serum cytokeratin-18 fragments reflect hepatocyte apoptosis and correlate with fibrotic NAFLD.", "protein": "Cytokeratin-18", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates enzyme secretion and serum half-life.", "mechanism": "Elevated AST is associated with hepatic injury and steatosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation influences enzyme activity and release.", "mechanism": "ALT elevation indicates hepatocellular damage in NAFLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation of apolipoproteins affects lipoprotein metabolism.", "mechanism": "Serum triglyceride levels are elevated in NAFLD due to hepatic lipid accumulation.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation may affect protein localization and function.", "mechanism": "Genetic variants in PNPLA3 increase susceptibility to hepatic steatosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12140639" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation influences membrane trafficking.", "mechanism": "TM6SF2 variants impair lipid export, promoting steatosis.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12140639" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation regulates EV formation and cargo sorting.", "mechanism": "EV proteins and microRNAs reflect liver injury and inflammation.", "protein": "Extracellular vesicle proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Glycosylation modulates transporter activity and stability.", "mechanism": "Altered bile acid transporter expression is linked to NAFLD progression.", "protein": "Bile acid transporters", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects lipid binding and transport.", "mechanism": "Altered plasma lipid profiles are indicative of metabolic syndrome and NAFLD.", "protein": "Plasma lipid species (apolipoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation impacts fragment release and detection.", "mechanism": "Serum cytokeratin-18 fragments are elevated in NASH due to increased apoptosis.", "protein": "Cytokeratin-18", "relationship_type": "biomarker", "source_pmcid": "PMC12140639" }, { "confidence": "high", "disease": "Pulmonary emphysema", "glycan_involvement": "AAT is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "AAT inhibits neutrophil elastase, preventing elastin degradation; deficiency leads to emphysema.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal/protective", "source_pmcid": "PMC12140657" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "Glycosylation affects AAT folding and secretion; Z variant misfolds and is degraded.", "mechanism": "Mutations in SERPINA1 gene reduce AAT levels, causing AATD.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12140657" }, { "confidence": "high", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation required for AAT function; altered glycosylation may affect inhibitory activity.", "mechanism": "AAT protects against protease-mediated lung damage; serum levels and activity correlate with disease severity.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "SLPI is glycosylated; glycosylation may modulate its antiprotease activity.", "mechanism": "SLPI inhibits neutrophil elastase, compensating for low AAT in COPD.", "protein": "Secretory leukocyte protease inhibitor (SLPI)", "protein_enriched": { "function": "Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:10702419, PubMed:2039600, PubMed:2110563, PubMed:24121345, PubMed:3462719, PubMed:3", "gene_name": "SLPI", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03973" }, "relationship_type": "protective/compensatory", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Elafin is glycosylated; glycosylation may affect secretion and function.", "mechanism": "Elafin inhibits neutrophil elastase, contributing to antiprotease defense in COPD.", "protein": "Elafin", "protein_enriched": { "function": "Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis. Has been shown to inhibit the alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic acetylcholine r", "gene_name": "PI3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19957" }, "relationship_type": "protective/compensatory", "source_pmcid": "PMC12140657" }, { "confidence": "high", "disease": "Pulmonary emphysema (AATD-related)", "glycan_involvement": "Therapeutic AAT is glycosylated; proper glycosylation is required for efficacy.", "mechanism": "AAT augmentation therapy restores antiprotease protection, delaying emphysema progression.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Pulmonary emphysema (non-AATD)", "glycan_involvement": "Altered glycosylation may affect AAT function in inflammation.", "mechanism": "Serum AAT and EIA levels reflect disease severity and inflammatory status.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation status may influence EIA/AAT ratio.", "mechanism": "EIA/AAT ratio serves as a biomarker for disease severity and prognosis.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Pulmonary emphysema", "glycan_involvement": "Therapeutic AAT glycosylation is critical for function.", "mechanism": "Oral or intravenous AAT or NE inhibitors may be considered in patients with low EIA despite normal AAT.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140657" }, { "confidence": "medium", "disease": "Pulmonary emphysema", "glycan_involvement": "Glycosylation may modulate susceptibility to oxidative damage.", "mechanism": "Oxidative modification of AAT (e.g., methionine oxidation) reduces its inhibitory function, contributing to disease.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12140657" }, { "confidence": "high", "disease": "Hyperphosphatemic familial tumoral calcinosis (HFTC)", "glycan_involvement": "FGF23 is O-glycosylated, which is essential for its secretion and stability.", "mechanism": "FGF23 deficiency or resistance leads to impaired phosphate excretion, causing hyperphosphatemia and ectopic calcification.", "protein": "Fibroblast growth factor 23", "relationship_type": "causal", "source_pmcid": "PMC12140817" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation affects FGF23 half-life and activity.", "mechanism": "FGF23 levels rise in CKD as a compensatory response to hyperphosphatemia; dysregulation contributes to mineral imbalance.", "protein": "Fibroblast growth factor 23", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12140817" }, { "confidence": "medium", "disease": "Hyperphosphatemic familial tumoral calcinosis (HFTC)", "glycan_involvement": "IL-1RA is glycosylated, which influences its stability and bioactivity.", "mechanism": "Anakinra (recombinant IL-1RA) reduces inflammation and pain in HFTC-associated calcinosis.", "protein": "Interleukin-1 receptor antagonist", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140817" }, { "confidence": "medium", "disease": "Uremic pericarditis (UP)", "glycan_involvement": "Pro-BNP is O-glycosylated, affecting its plasma levels and detection.", "mechanism": "Elevated pro-BNP reflects cardiac stress and is used to monitor UP severity.", "protein": "Pro-B-type natriuretic peptide (pro-BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12140817" }, { "confidence": "medium", "disease": "Secondary hyperparathyroidism", "glycan_involvement": "Glycosylation modulates FGF23 secretion and function.", "mechanism": "FGF23 dysregulation contributes to altered vitamin D metabolism and secondary hyperparathyroidism in CKD/HFTC.", "protein": "Fibroblast growth factor 23", "relationship_type": "causal", "source_pmcid": "PMC12140817" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Decreased albumin indicates impaired liver synthetic function post-surgery.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect enzyme stability and clearance.", "mechanism": "Elevated AST reflects hepatocellular injury after abdominal surgery.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation can modulate enzyme activity.", "mechanism": "Increased ALT is a marker of liver cell injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Hyperlactacidemia", "glycan_involvement": "Lactate is a glycolytic product; not a glycoprotein but related to glycometabolism.", "mechanism": "Elevated lactate indicates tissue hypoperfusion or metabolic stress.", "protein": "Lactate", "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "medium", "disease": "Renal failure", "glycan_involvement": "Glycosylation affects renal handling and clearance.", "mechanism": "Low albumin may reflect protein loss or impaired synthesis in renal dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Renal failure", "glycan_involvement": "Indirect; SCr is not a glycoprotein but reflects renal handling of glycoproteins.", "mechanism": "Elevated SCr indicates impaired renal filtration.", "protein": "Serum Creatinine (SCr)", "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Metabolic acidosis", "glycan_involvement": "Related to glycolytic flux and glycoprotein metabolism.", "mechanism": "Lactate accumulation can contribute to acid-base imbalance.", "protein": "Lactate", "relationship_type": "causal", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Hyperglycemia leads to non-enzymatic glycation of proteins.", "mechanism": "Elevated glucose is a hallmark of diabetes; impacts glycoprotein glycation.", "protein": "Glucose", "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "medium", "disease": "Postoperative complications", "glycan_involvement": "Glycosylation status may affect immune response and healing.", "mechanism": "Low albumin is associated with increased risk of complications.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "medium", "disease": "Metabolic acidosis", "glycan_involvement": "Indirect; reflects altered glycoprotein metabolism.", "mechanism": "Elevated BB indicates ketone body accumulation and acidosis.", "protein": "Beta-hydroxybutyrate (BB)", "relationship_type": "biomarker", "source_pmcid": "PMC12140924" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Catalase is glycosylated, which affects its stability and secretion in tissues.", "mechanism": "Catalase activity reduces ROS, protecting cells from oxidative damage and promoting wound healing.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140961" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "SOD glycosylation modulates enzyme activity and localization.", "mechanism": "SOD activity scavenges superoxide radicals, reducing oxidative stress and aiding tissue repair.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "CD31 glycosylation regulates cell adhesion and angiogenic signaling.", "mechanism": "CD31 marks endothelial cells; increased angiogenesis (CD31+) correlates with improved wound healing.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Paxillin glycosylation influences focal adhesion dynamics.", "mechanism": "Restoration of paxillin expression supports cytoskeletal remodeling and cell migration in wound healing.", "protein": "Paxillin", "protein_enriched": { "function": "Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion", "gene_name": "PXN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49023" }, "relationship_type": "protective", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation affects CD86 surface expression and immune signaling.", "mechanism": "CD86 marks pro-inflammatory M1 macrophages; high levels indicate chronic inflammation and poor healing.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation modulates CD206 ligand binding and macrophage polarization.", "mechanism": "CD206 marks anti-inflammatory M2 macrophages; increased levels correlate with resolution of inflammation and tissue repair.", "protein": "CD206 (MRC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Chronic wound", "glycan_involvement": "Altered glycosylation may reduce catalase stability in chronic wounds.", "mechanism": "Catalase activity is impaired in chronic wounds, leading to excess ROS and delayed healing.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Chronic wound", "glycan_involvement": "Glycosylation status affects CD31-mediated cell interactions.", "mechanism": "CD31+ endothelial cells indicate angiogenesis, which is reduced in chronic wounds.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140961" }, { "confidence": "low", "disease": "Thrombosis", "glycan_involvement": "Aberrant glycosylation can affect anti-thrombotic properties.", "mechanism": "CD31 regulates platelet-endothelial interactions; altered glycosylation may contribute to thrombosis risk.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "causal", "source_pmcid": "PMC12140961" }, { "confidence": "medium", "disease": "Chronic wound", "glycan_involvement": "Glycosylation modulates immune cell activation.", "mechanism": "Elevated CD86+ M1 macrophages indicate persistent inflammation and impaired healing.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12140961" }, { "confidence": "high", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "PINK1 upregulation leads to excessive mitophagy, promoting podocyte apoptosis and DKD progression.", "protein": "PINK1", "relationship_type": "causal", "source_pmcid": "PMC12141005" }, { "confidence": "high", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "Parkin, recruited by PINK1, mediates mitophagy; its overactivation contributes to podocyte injury in DKD.", "protein": "Parkin", "protein_enriched": { "function": "Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed", "gene_name": "PRKN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60260" }, "relationship_type": "causal", "source_pmcid": "PMC12141005" }, { "confidence": "high", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "Elevated LC3-II/LC3-I ratio indicates increased mitophagy in DKD.", "protein": "LC3 (MAP1LC3B)", "relationship_type": "biomarker", "source_pmcid": "PMC12141005" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "ATG5 upregulation reflects increased autophagy/mitophagy in DKD.", "protein": "ATG5", "relationship_type": "biomarker", "source_pmcid": "PMC12141005" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "Beclin-1 elevation is associated with increased mitophagy in DKD.", "protein": "Beclin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12141005" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "Not specified", "mechanism": "TOM20/LC3 co-localization marks mitophagy activation in DKD podocytes.", "protein": "TOM20", "protein_enriched": { "function": "Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide", "gene_name": "TOMM20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q15388" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141005" }, { "confidence": "medium", "disease": "Podocyte Injury", "glycan_involvement": "Not specified", "mechanism": "Bcl-2 downregulation in DKD podocytes correlates with increased apoptosis.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12141005" }, { "confidence": "medium", "disease": "Podocyte Injury", "glycan_involvement": "Not specified", "mechanism": "Bax upregulation promotes podocyte apoptosis in DKD.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC12141005" }, { "confidence": "high", "disease": "Proteinuria", "glycan_involvement": "Not specified", "mechanism": "Inhibition of PINK1 reduces proteinuria by protecting podocytes from apoptosis.", "protein": "PINK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141005" }, { "confidence": "high", "disease": "Proteinuria", "glycan_involvement": "Not specified", "mechanism": "Downregulation of Parkin reduces mitophagy and proteinuria in DKD.", "protein": "Parkin", "protein_enriched": { "function": "Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed", "gene_name": "PRKN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60260" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141005" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "AFP is an N-glycosylated glycoprotein; glycosylation is essential for its secretion and stability in serum.", "mechanism": "Elevated serum AFP (>20 ng/mL) is associated with advanced tumor stage, larger tumor size, increased lymph node and distant metastasis, and poor prognosis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may influence AFP's interaction with tumor microenvironment and immune evasion.", "mechanism": "AFP may reflect hepatic differentiation in gastric tumor cells, which is linked to aggressive tumor behavior and metastatic potential.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141012" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation is required for proper folding and function of AFP in these interactions.", "mechanism": "AFP acts as a co-chaperone of HSP90, stabilizing oncoproteins c-MYC and c-MET, facilitating tumor progression.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "causal", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Serum detection relies on glycosylated AFP forms.", "mechanism": "AFP positivity is an independent prognostic factor for overall survival (HR=1.8), outperforming TNM staging alone in predictive models.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Gastric hepatoid adenocarcinoma", "glycan_involvement": "N-glycosylation is critical for AFP secretion and detection.", "mechanism": "AFP is highly elevated in this subtype, reflecting hepatic differentiation and aggressive clinical course.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "N-glycosylation is essential for serum stability and immunoassay detection.", "mechanism": "AFP is a well-established marker for diagnosis and prognosis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may affect AFP's role in metastatic niche formation.", "mechanism": "AFP-positive gastric cancer is associated with higher rates of liver metastasis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Germ cell tumors", "glycan_involvement": "N-glycosylation required for secretion and detection.", "mechanism": "AFP is elevated in certain germ cell tumors, aiding diagnosis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation ensures AFP's detectability in serum assays.", "mechanism": "AFP inclusion in a nomogram improves survival prediction accuracy (AUC 0.80\u20130.84 vs. 0.70\u20130.74 for TNM alone).", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141012" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may modulate AFP's signaling interactions.", "mechanism": "AFP may activate Wnt signaling, promoting tumor cell growth and aggression.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "causal", "source_pmcid": "PMC12141012" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is heavily N-glycosylated, affecting its stability and function.", "mechanism": "CRP levels predict inflammation and cardiovascular risk; watercress supplementation reduces CRP.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141087" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and activity.", "mechanism": "TNF-\u03b1 drives inflammatory signaling; watercress reduces TNF-\u03b1 levels.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141087" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "IL-6 glycosylation affects secretion and receptor interaction.", "mechanism": "IL-6 is elevated in diabetes and predicts mortality; watercress lowers IL-6.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "IL-1 glycosylation influences cytokine activity.", "mechanism": "IL-1 promotes joint inflammation; watercress modulates IL-1 levels.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "SOD glycosylation affects enzyme stability.", "mechanism": "SOD detoxifies ROS, protecting against DNA damage; watercress increases SOD activity.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "GPx glycosylation modulates antioxidant function.", "mechanism": "GPx reduces oxidative stress in liver; watercress increases GPx activity.", "protein": "Glutathione peroxidase (GPx)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles", "gene_name": "Gsta4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24472" }, "relationship_type": "protective", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Nephrotoxicity", "glycan_involvement": "CAT glycosylation impacts enzyme activity.", "mechanism": "CAT detoxifies peroxides in kidney; watercress supports CAT activity.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Oxidative modification of glycoproteins alters function.", "mechanism": "PCs indicate oxidative protein damage; watercress reduces PC formation.", "protein": "Protein carbonyls (PC)", "relationship_type": "biomarker", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "MDA adducts can modify glycoproteins, impairing function.", "mechanism": "MDA-modified proteins reflect lipid peroxidation; watercress lowers MDA.", "protein": "Malondialdehyde-modified proteins (MDA)", "relationship_type": "biomarker", "source_pmcid": "PMC12141087" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "iNOS glycosylation regulates enzyme activity.", "mechanism": "iNOS drives NO production and inflammation; watercress inhibits iNOS via NF-kB pathway.", "protein": "Nitric oxide synthase (iNOS)", "relationship_type": "causal", "source_pmcid": "PMC12141087" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "IRS-1 is glycosylated, which affects its stability and signaling; geniposide may indirectly influence glycosylation via metabolic regulation.", "mechanism": "Geniposide increases IRS-1 protein levels, enhancing insulin signaling and glucose uptake, ameliorating insulin resistance in NAFLD.", "protein": "IRS-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "GLUT1 glycosylation is essential for membrane localization and function.", "mechanism": "Geniposide upregulates GLUT1, promoting glucose uptake and reducing hepatic steatosis.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "TLR4 glycosylation is required for ligand recognition and signaling.", "mechanism": "Geniposide inhibits TLR4/NF-\u03baB pathway, reducing hepatic inflammation and progression of NAFLD.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "RAGE is a glycoprotein; glycosylation affects ligand binding and signaling.", "mechanism": "AGE-RAGE signaling promotes oxidative stress and steatosis; geniposide modulates this pathway to slow NAFLD progression.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "HO-1 glycosylation may affect stability and activity.", "mechanism": "Geniposide activates Nrf2/HO-1 pathway, increasing antioxidant defense and reducing fibrosis.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Geniposide inhibits UCP2-mediated proton leakage, restoring mitochondrial function and reducing hepatic steatosis.", "protein": "UCP2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O88567" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "GLUT2 glycosylation is important for function.", "mechanism": "Geniposide increases GLUT2 levels, enhancing glucose-stimulated insulin secretion and improving insulin sensitivity.", "protein": "GLUT2", "protein_enriched": { "function": "Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting secretion and activity.", "mechanism": "IL-1\u03b2 promotes hepatic inflammation; geniposide reduces IL-1\u03b2 secretion via inhibition of NLRP3 inflammasome.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12141232" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "SREBP-1c glycosylation modulates its activity.", "mechanism": "Geniposide inhibits SREBP-1c, reducing fatty acid synthesis and hepatic lipid accumulation.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141232" }, { "confidence": "medium", "disease": "Steatohepatitis", "glycan_involvement": "HO-1 glycosylation may affect its antioxidant function.", "mechanism": "Geniposide-induced HO-1 expression reduces oxidative stress and prevents progression to steatohepatitis.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12141232" }, { "confidence": "high", "disease": "Malignant Pleural Mesothelioma (MPM)", "glycan_involvement": "FUCA1 degrades terminal fucose residues on glycoconjugates, affecting glycosylation patterns relevant to tumor progression.", "mechanism": "Low FUCA1 expression correlates with poor prognosis; FUCA1 inhibits proliferation, invasion, migration, and EMT in MPM cells via PI3K-AKT pathway.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "biomarker/therapeutic_target/protective", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Thyroid Cancer", "glycan_involvement": "Altered fucosylation due to FUCA1 deficiency impacts tumor biology.", "mechanism": "Low FUCA1 expression associated with worsened prognosis.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Colon Cancer", "glycan_involvement": "Aberrant glycosylation due to reduced FUCA1 activity.", "mechanism": "Low FUCA1 expression associated with worsened prognosis.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Altered glycan degradation affects tumor cell behavior.", "mechanism": "Low FUCA1 expression associated with worsened prognosis.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Renal Cancer", "glycan_involvement": "Glycosylation changes mediated by FUCA1 promote cell death.", "mechanism": "FUCA1 expression induces apoptosis in renal tumor cells.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "Glycosylation modification by FUCA1 affects signaling pathways.", "mechanism": "FUCA1 inhibits EGFR signaling and AKT phosphorylation, suppressing proliferation.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", 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"function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "causal", "source_pmcid": "PMC12141270" }, { "confidence": "high", "disease": "Malignant Pleural Mesothelioma (MPM)", "glycan_involvement": "FUCA1-mediated glycosylation suppresses EMT and tumor progression.", "mechanism": "FUCA1 inhibits EMT via PI3K-AKT signaling, reducing metastasis and drug resistance.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "causal", "source_pmcid": "PMC12141270" }, { "confidence": "medium", "disease": "Urothelial Carcinoma", "glycan_involvement": "Glycosylation status may affect immune recognition and therapy response.", "mechanism": "Low FUCA1 expression correlates with poor response to immunotherapy.", "protein": "FUCA1", "protein_enriched": { "function": "Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins", "gene_name": "FUCA1", "glycan_count": 53, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04854VP", "G05049YU", "G07755XJ", "G10488MI", "G11314AS", "G14972EH", "G15664MX", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G34989PA", "G35253PZ", "G40206WX", "G41247ZX", "G43223CG", "G45395BF", "G45495MK", "G47644PP", "G50282JC", "G58954YZ", "G61256FT", "G64409MC", "G72747WU", "G73968GN", "G74724QE", "G75418YA", "G76295SF", "G77547TA", "G77669RF", "G84452RH", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G49108TO", "G01650EU", "G06110VR", "G28681TP", "G36666WX", "G39188ZX", "G62765YT", "G70375MX", "G70441OD", "G78790NZ", "G80920RR", "G82443XX", "G84349RE", "G92050GC", "G96091TT" ], "uniprot_id": "P04066" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141270" }, { "confidence": "high", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "Fc glycosylation modulates immune complex formation and effector function.", "mechanism": "IgG is targeted by RF and forms immune complexes; IgG-ACPA is a hallmark autoantibody in seropositive RA.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141282" }, { "confidence": "high", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "IgA glycosylation affects mucosal immunity and antibody stability.", "mechanism": "IgA-ACPA and IgA-RF are produced in mucosal tissues and appear before joint symptoms.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC12141282" }, { "confidence": "high", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "ACPA glycosylation influences antigen binding and immune activation.", "mechanism": "ACPA production is triggered by citrullinated proteins in inflamed lungs, breaking tolerance and driving RA.", "protein": "Anti-citrullinated protein antibody (ACPA)", "relationship_type": "causal", "source_pmcid": "PMC12141282" }, { "confidence": "high", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "RF glycosylation modulates immune complex formation.", "mechanism": "RF targets IgG Fc, forming immune complexes that drive inflammation.", "protein": "Rheumatoid Factor (RF)", "relationship_type": "biomarker", "source_pmcid": "PMC12141282" }, { "confidence": "medium", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "Heavily glycosylated spike protein enhances immune recognition and molecular mimicry.", "mechanism": "Spike glycoprotein shares epitopes with pulmonary surfactant protein, triggering cross-reactive autoimmunity and ACPA production.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12141282" }, { "confidence": "medium", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Cross-reactivity with SARS-CoV-2 spike glycoprotein may trigger autoimmunity.", "protein": "Pulmonary 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"mechanism": "SLAMF7+ macrophages are hyperactivated in RA and COVID-19, amplifying inflammation.", "protein": "SLAMF7", "protein_enriched": { "function": "Probable immunoglobulin-like cell surface receptor. On binding with CD47, mediates cell-cell adhesion. Engagement on T-cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-", "gene_name": "SIRPG", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P1W8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141282" }, { "confidence": "medium", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "N-glycosylation may regulate inflammasome assembly and stability.", "mechanism": "NLRP3 inflammasome activation by infection or ACPA leads to IL-1\u03b2/IL-18 production and inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12141282" }, { "confidence": "high", "disease": "Seropositive Rheumatoid Arthritis", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "IL-6 drives Th17/Treg imbalance and autoantibody production, exacerbating RA.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141282" }, { "confidence": "high", "disease": "Infertility in diabetic women", "glycan_involvement": "Altered glycosylation affects anti-adhesive properties.", "mechanism": "Overexpression in endometrial epithelial cells impairs embryo adhesion and endometrial receptivity.", "protein": "Mucin 1", "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Endometrial hyperplasia", "glycan_involvement": "O-glycosylation by GALNT2 modulates receptor function.", "mechanism": "GALNT2-mediated glycosylation enhances EGFR activity, promoting endometrial cell proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Infertility in diabetic women", "glycan_involvement": "Integrin glycosylation modulates cell-matrix interactions.", "mechanism": "Diabetes increases integrin gene expression, leading to disorganized cell adhesion during implantation.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "high", "disease": "Recurrent implantation failure", "glycan_involvement": "LIF is a glycoprotein; glycosylation required for secretion and function.", "mechanism": "Decreased LIF expression in diabetic endometrium impairs implantation.", "protein": "LIF", "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Infertility in diabetic women", "glycan_involvement": "IGF-1 is a glycoprotein; glycosylation affects stability and receptor binding.", "mechanism": "Reduced IGF-1 expression in endometrial and decidual cells impairs receptivity and implantation.", "protein": "IGF-1", "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Infertility in diabetic women", "glycan_involvement": "Glycosylation modulates cytokine secretion and activity.", "mechanism": "Overexpression in diabetic uterus creates nonreceptive endometrium and embryo loss.", "protein": "Interferon gamma (IFNG)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "IFNG", "glycan_count": 41, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G08520NM", "G10219AA", "G14260UH", "G18938DW", "G20030CU", "G20425TQ", "G23453IV", "G23863VK", "G29011JC", "G29857RC", "G31936TA", "G33609NS", "G36191CD", "G39188ZX", "G39213VZ", "G40702WU", "G45359RY", "G46687AB", "G47012YE", "G49874UX", "G49889OJ", "G50045TK", "G52064IJ", "G55220VL", "G60145BJ", "G61751GZ", "G63889NK", "G64527OM", "G68668TB", "G72797UR", "G75727PF", "G78059CC", "G79809MM", "G80858MF", "G80966KZ", "G81295CK", "G83161QT", "G86357DX", "G90093AU" ], "uniprot_id": "P01579" }, "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Endometrial carcinoma", "glycan_involvement": "N-glycosylation affects cell-cell adhesion.", "mechanism": "Downregulation by high glucose enhances cell invasion and cancer progression.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Endometrial carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Upregulation by high glucose promotes epithelial-mesenchymal transition and invasion.", "protein": "Snail", "protein_enriched": { "function": "Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration (PubMed:10655587, PubMed:15647282, ", "gene_name": "SNAI1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95863" }, "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "low", "disease": "Infertility in diabetic women", "glycan_involvement": "Beclin-1 is glycosylated; modification may affect function.", "mechanism": "Decreased Beclin-1 impairs autophagy, affecting endometrial receptivity.", "protein": "Beclin-1", "relationship_type": "causal", "source_pmcid": "PMC12141299" }, { "confidence": "medium", "disease": "Endometrial hyperplasia", "glycan_involvement": "O-glycosylation of EGFR.", "mechanism": "GALNT2 modifies EGFR glycosylation, enhancing proliferation; potential target to modulate endometrial growth.", "protein": "GALNT2", "protein_enriched": { "function": "Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spect", "gene_name": "GALNT2", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "Q10471" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141299" }, { "confidence": "high", "disease": "Renal cell carcinoma", "glycan_involvement": "IL-2 is a glycoprotein; glycosylation affects stability and receptor interaction.", "mechanism": "IL-2 stimulates immune effector cells to attack tumor cells.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "high", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation modulates IL-2 bioactivity and half-life.", "mechanism": "IL-2 activates cytotoxic lymphocytes for tumor killing.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Vascular leak syndrome (capillary leak syndrome)", "glycan_involvement": "Glycosylation may influence receptor binding and toxicity.", "mechanism": "IL-2 interaction with trimeric receptor on endothelial cells disrupts vascular integrity.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "causal", "source_pmcid": "PMC12141302" }, { "confidence": "high", "disease": "Advanced solid tumors", "glycan_involvement": "Mutein is a glycoprotein; glycosylation likely affects pharmacokinetics and immunogenicity.", "mechanism": "Mutein preferentially stimulates CD8+ T and NK cells, enhancing antitumor immunity.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation may impact mutein stability and immune activation.", "mechanism": "Mutein induced partial response in metastatic triple-negative breast cancer patient.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Ovarian adenocarcinoma", "glycan_involvement": "Glycosylation may modulate mutein's immune effects.", "mechanism": "Mutein treatment led to disease control and improved response to subsequent chemotherapy.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Glycosylation may affect mutein's pharmacodynamics.", "mechanism": "Mutein associated with prolonged survival in metastatic pancreatic cancer.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Glycosylation may influence immune cell targeting.", "mechanism": "Mutein associated with long-term survival in advanced renal cell carcinoma.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Vascular leak syndrome (capillary leak syndrome)", "glycan_involvement": "Altered glycosylation may contribute to reduced endothelial toxicity.", "mechanism": "Mutein does not activate the alpha chain, reducing risk of vascular leak syndrome.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "protective", "source_pmcid": "PMC12141302" }, { "confidence": "medium", "disease": "Metastatic melanoma", "glycan_involvement": "Glycosylation may affect immune activation and half-life.", "mechanism": "Mutein is being evaluated for efficacy in metastatic melanoma in phase II.", "protein": "Interleukin-2 mutein (no-alpha IL-2 mutein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141302" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TLR4 is a glycoprotein; glycosylation affects ligand recognition and signaling.", "mechanism": "AS-IV inhibits TLR4/NF-\u03baB signaling, suppressing M1 macrophage polarization and reducing inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "NF-\u03baB activation is modulated by upstream glycoprotein receptors.", "mechanism": "AS-IV suppresses NF-\u03baB activation, reducing pro-inflammatory cytokine production and joint damage.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "AS-IV reduces IL-6 secretion by inhibiting M1 macrophage polarization.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "TNF-\u03b1 is glycosylated, influencing receptor binding and activity.", "mechanism": "AS-IV lowers TNF-\u03b1 levels, alleviating inflammation and tissue damage.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "IL-10 glycosylation modulates anti-inflammatory activity.", "mechanism": "AS-IV promotes M2 macrophage polarization, increasing IL-10 and facilitating neural repair.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12141326" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "TGF-\u03b2 glycosylation affects receptor interaction and signaling.", "mechanism": "AS-IV regulates TGF-\u03b2 signaling, reducing macrophage adhesion and migration.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Ischemic stroke", "glycan_involvement": "PPAR\u03b3 activity is modulated by glycoprotein signaling cascades.", "mechanism": "AS-IV activates PPAR\u03b3, shifting macrophages to M2 phenotype and promoting tissue repair.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "medium", "disease": "Intestinal mucositis", "glycan_involvement": "STAT1 activation is downstream of glycoprotein cytokine receptors.", "mechanism": "AS-IV inhibits STAT1, reducing M1 polarization and inflammation.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "NLRP3 function is modulated by upstream glycoprotein signaling.", "mechanism": "CAG inhibits NLRP3 inflammasome-mediated pyroptosis, reducing skin inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "STAT6 activation is regulated by glycoprotein cytokine receptors.", "mechanism": "AS-IV promotes STAT6 activation, enhancing M2 polarization and reducing fibrosis.", "protein": "STAT6", "protein_enriched": { "function": "Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling", "gene_name": "STAT6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42226" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141326" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "N-glycosylation of PD-L1 modulates its stability and immune recognition.", "mechanism": "PD-L1 is targeted by immune checkpoint inhibitors to restore anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "N-glycosylation affects PD-1 surface expression and ligand binding.", "mechanism": "PD-1 is blocked by antibodies to enhance T cell-mediated anti-tumor response.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "N-glycosylation is essential for VEGF-A secretion and receptor interaction.", "mechanism": "VEGF-A promotes angiogenesis; inhibition reduces tumor vascularization.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "Therapeutic antibody glycosylation affects efficacy and half-life.", "mechanism": "Bevacizumab binds VEGF-A, blocking angiogenesis.", "protein": "Bevacizumab", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "Fc glycosylation modulates antibody effector function.", "mechanism": "Atezolizumab blocks PD-L1, restoring T cell activity.", "protein": "Atezolizumab", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Unresectable hepatocellular carcinoma (uHCC)", "glycan_involvement": "Fc glycosylation impacts antibody stability and immune activation.", "mechanism": "Sintilimab blocks PD-1, enhancing immune response.", "protein": "Sintilimab", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered glycosylation patterns of AFP are used for HCC diagnosis.", "mechanism": "Elevated AFP is associated with HCC tumor burden and prognosis.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12141330" }, { "confidence": "medium", "disease": "Immune-related hepatitis", "glycan_involvement": "Glycosylation may affect PD-L1 immunogenicity.", "mechanism": "Immune checkpoint blockade can trigger immune-mediated hepatitis.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12141330" }, { "confidence": "medium", "disease": "Immune-related dermatitis", "glycan_involvement": "Glycosylation may modulate PD-1 immune tolerance.", "mechanism": "PD-1 blockade can lead to immune-related skin adverse events.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12141330" }, { "confidence": "medium", "disease": "Immune-related nephritis", "glycan_involvement": "Glycosylation may influence PD-1 function in peripheral tolerance.", "mechanism": "PD-1 inhibition can cause immune-mediated nephritis.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12141330" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Downregulated in ccRCC; upregulation inhibits cell proliferation, invasion, and metastasis via suppression of STAT3 signaling and lipid droplet formation.", "protein": "SLC25A4", "protein_enriched": { "function": "ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:21586654, PubMed:27693233). Cycles between the cytoplasmi", "gene_name": "SLC25A4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12235" }, "relationship_type": "protective", "source_pmcid": "PMC12141529" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Glycosylation affects membrane localization and drug transport.", "mechanism": "Efflux pump for antineoplastic drugs; associated with chemotherapy resistance and prognosis.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "Glycosylation modulates function.", "mechanism": "Polymorphisms linked to prognosis and drug resistance.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Promotes cholesteryl transfer, raising cancer risk.", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "causal", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Oropharyngeal cancer", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Cholesteryl transfer activity linked to increased risk.", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "causal", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Polymorphism (rs2242480) associated with increased risk; involved in steroid metabolism.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "causal", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Suppresses migration, invasion, and metastasis via inhibition of Akt signaling.", "protein": "DMGDH", "relationship_type": "protective", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Colorectal cancer liver metastasis", "glycan_involvement": "Glycosylation essential for secretion and coagulation activity.", "mechanism": "Overexpressed and acts as a hub gene in metastasis.", "protein": "F2 (Prothrombin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12141529" }, { "confidence": "medium", "disease": "Prostate cancer recurrence", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Associated with recurrence after prostatectomy; metabolizes carcinogens.", "protein": "UGT1A10", "relationship_type": "biomarker", "source_pmcid": "PMC12141529" }, { "confidence": "low", "disease": "Lung adenocarcinoma", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Overexpression inhibits growth, viability, and migration in cell lines.", "protein": "SLC25A4", "protein_enriched": { "function": "ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:21586654, PubMed:27693233). Cycles between the cytoplasmi", "gene_name": "SLC25A4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12235" }, "relationship_type": "protective", "source_pmcid": "PMC12141529" }, { "confidence": "high", "disease": "Age-related cataract (ARC)", "glycan_involvement": "N-glycosylation required for IL-6 secretion and stability.", "mechanism": "Elevated IL-6 as part of SASP promotes proinflammatory microenvironment in lens epithelial cells, contributing to ARC progression.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Age-related cataract (ARC)", "glycan_involvement": "N-glycosylation facilitates IL-1\u03b2 maturation and secretion.", "mechanism": "Increased IL-1\u03b2 secretion in SASP drives inflammation and lens degeneration.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Age-related cataract (ARC)", "glycan_involvement": "N-glycosylation essential for TGF-\u03b2 folding and activity.", "mechanism": "TGF-\u03b2 upregulation in SASP promotes fibrosis and lens opacity.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Age-related cataract (ARC)", "glycan_involvement": "No direct glycosylation; regulation is phosphorylation-dependent.", "mechanism": "p53 phosphorylation and activation drive cellular senescence and apoptosis in lens epithelial cells; Fe-curcumin nanozymes inhibit p53 phosphorylation, reducing ARC progression.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Cellular senescence", "glycan_involvement": "No glycosylation reported.", "mechanism": "p21 upregulation marks cell cycle arrest and senescence in lens epithelial cells.", "protein": "p21", "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Apoptosis", "glycan_involvement": "No glycosylation reported.", "mechanism": "BAX upregulation mediates mitochondrial apoptosis in lens epithelial cells under oxidative stress.", "protein": "BAX", "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Apoptosis", "glycan_involvement": "No glycosylation reported.", "mechanism": "Activation of caspase-3 is a hallmark of apoptosis in lens epithelial cells during ARC.", "protein": "Cleaved caspase-3 (C-c3)", "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "No glycosylation reported.", "mechanism": "Cyclin D upregulation indicates cell cycle dysregulation and senescence in lens epithelial cells.", "protein": "Cyclin D", "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "medium", "disease": "Cellular senescence", "glycan_involvement": "No glycosylation reported.", "mechanism": "Cyclin B1 downregulation reflects G2/M cell cycle arrest in senescent lens epithelial cells.", "protein": "Cyclin B1", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G2/M (mitosis) transition", "gene_name": "CCNB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14635" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141545" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "No glycosylation reported.", "mechanism": "ATM activation leads to p53 phosphorylation, promoting senescence and apoptosis in lens epithelial cells under oxidative stress.", "protein": "ATM", "protein_enriched": { "function": "Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a ", "gene_name": "ATM", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q13315" }, "relationship_type": "causal", "source_pmcid": "PMC12141545" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "Potential glycosylation affects trafficking and stability.", "mechanism": "Upregulated in MLIV plasma; correlates with motor dysfunction and muscle tone; involved in autophagy and synaptic function.", "protein": "GABARAP", "protein_enriched": { "function": "Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton (PubMed:9892355). Involved in autophagy: while LC3s are involved in ", "gene_name": "GABARAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect secretion and function.", "mechanism": "Upregulated in MLIV plasma; correlates with disease severity; involved in Ca2+/Zn2+ regulation and astrocytic pathology.", "protein": "S100A6", "protein_enriched": { "function": "May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role i", "gene_name": "S100A6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06703" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation required for lysosomal targeting and activity.", "mechanism": "Upregulated in MLIV plasma and mouse brain; lysosomal enzyme involved in glycan degradation.", "protein": "GLB1", "protein_enriched": { "function": "Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans", "gene_name": "GLB1", "glycan_count": 82, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G02886BB", "G05724UK", "G07246CJ", "G11314AS", "G23719VF", "G25079LO", "G28541PG", "G28681TP", "G31852PQ", "G34029GR", "G35029YA", "G39446WN", "G41247ZX", "G43669FQ", "G47644PP", "G47950XN", "G56625RB", "G62765YT", "G63041LO", "G70223PD", "G70441OD", "G73968GN", "G80920RR", "G84225JN", "G90575OW", "G90659AW", "G92050GC", "G92275SC", "G92406TI", "G95177YH", "G00912UN", "G01650EU", "G06110VR", "G06247RL", "G08918WF", "G10773YW", "G11115RO", "G11870QZ", "G11911BT", "G15664MX", "G20210JR", "G23294PN", "G23984SE", "G27915IV", "G28465XX", "G29299MO", "G30248BL", "G31986NC", "G34989PA", "G36442WJ", "G37399XV", "G37412TK", "G37995HC", "G39188ZX", "G40574BA", "G40834TG", "G41071NU", "G42124LM", "G44753VC", "G45395BF", "G49018RC", "G50282JC", "G51640FO", "G53075ES", "G59324HL", "G66621EA", "G70232NH", "G72735IY", "G74724QE", "G83460ZZ", "G83633GK", "G86182NS", "G87661QW", "G92135MA", "G95865ZB", "G96091TT", "G98611JV", "G36512SK", "G72291OX", "G49108TO" ], "uniprot_id": "P16278" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation essential for lysosomal function.", "mechanism": "Upregulated in MLIV plasma and mouse brain; lysosomal enzyme for glycosaminoglycan catabolism.", "protein": "GNS", "protein_enriched": { "function": "Hydrolyzes 6-sulfate groups in N-acetyl-d-glucosaminide units of heparin sulfate and keratan sulfate", "gene_name": "GNS", "glycan_count": 116, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G00912UN", "G01521EA", "G04854VP", "G05962QB", "G07810QS", "G11101UV", "G12745LE", "G15664MX", "G20577LS", "G20706XG", "G26377UA", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G49755GI", "G50282JC", "G53075ES", "G53641QT", "G62765YT", "G63136LV", "G63980BQ", "G76915KR", "G77547TA", "G80920RR", "G90575OW", "G90659AW", "G94470IW", "G99679NM", "G20991XV", "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G11870QZ", "G14669DU", "G23719VF", "G27058EU", "G28681TP", "G35029YA", "G36379GD", "G39188ZX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G49955PK", "G57317CE", "G57776ZU", "G59626AS", "G65184UU", "G72790NZ", "G74724QE", "G83460ZZ", "G84349RE", "G85269DF", "G86182NS", "G87661QW", "G92050GC", "G92275SC", "G95177YH", "G95865ZB", "G02886BB", "G10486CT", "G36442WJ", "G43669FQ", "G49018RC", "G56307ZW", "G70888PK", "G72747WU", "G80479JV", "G81124ET", "G87389XI", "G45504EY", "G49108TO", "G05724UK", "G06110VR", "G39446WN", "G56770VP", "G59924QI", "G70101JE", "G72735IY", "G92406TI", "G09528DL", "G10773YW", "G72787SB", "G00406II", "G01485JJ", "G01650EU", "G23863VK", "G25637MV", "G27126ED", "G33609NS", "G37995HC", "G51640FO", "G64527OM", "G70223PD", "G95995BI", "G08918WF", "G18183SM", "G30769VJ", "G31544HA", "G34989PA", "G37399XV", "G37412TK", "G64409MC", "G71463BG", "G78790NZ", "G90382BL", "G92135MA", "G35541EV", "G02628JF", "G26915XM", "G52890YB", "G57888GL" ], "uniprot_id": "P15586" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation affects enzyme stability and trafficking.", "mechanism": "Upregulated in MLIV plasma and mouse brain; lysosomal protease involved in protein and glycoprotein degradation.", "protein": "CTSB", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins (PubMed:12220505). Cleaves matrix extracellular phosphoglycoprotein MEPE (PubMed:12220505). Involv", "gene_name": "CTSB", "glycan_count": 12, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G71784JC", "G31852PQ", "G41071NU", "G41247ZX", "G45495MK", "G62765YT", "G79666IR", "G80920RR", "G83460ZZ", "G84452RH", "G87661QW" ], "uniprot_id": "P07858" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation required for lysosomal localization.", "mechanism": "Upregulated in MLIV plasma and mouse brain; involved in sphingolipid metabolism.", "protein": "ASAH1", "protein_enriched": { "function": "Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:11451951, PubMed:15655246, PubMed:26898341, PubMed:36752535, Pub", "gene_name": "ASAH1", "glycan_count": 121, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G07246CJ", "G10486CT", "G11101UV", "G11870QZ", "G12313PD", "G18647XP", "G20210JR", "G26330YA", "G28541PG", "G28681TP", "G31852PQ", "G33416PL", "G34029GR", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G43223CG", "G46503DX", "G49955PK", "G50282JC", "G57776ZU", "G62765YT", "G62894KT", "G63136LV", "G64409MC", "G64527OM", "G70375MX", "G72747WU", "G80920RR", "G82119TF", "G82463GQ", "G83460ZZ", "G84349RE", "G84820NF", "G85282JO", "G85677PP", "G88891KO", "G90575OW", "G90659AW", "G92050GC", "G92275SC", "G95865ZB", "G00273SJ", "G00406II", "G00912UN", "G01485JJ", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08918WF", "G10846ZT", "G11314AS", "G13191RB", "G14669DU", "G14972EH", "G17208MA", "G22310AV", "G22572EH", "G23294PN", "G23719VF", "G24528MX", "G27058EU", "G31028YV", "G35029YA", "G37412TK", "G40206WX", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G45395BF", "G45504EY", "G46524LG", "G47644PP", "G48414YA", "G49018RC", "G49642SA", "G50757KG", "G51640FO", "G51653BI", "G54010QB", "G57317CE", "G58954YZ", "G59626AS", "G60923RB", "G65184UU", "G69521XL", "G70101JE", "G70619PT", "G72291OX", "G72787SB", "G72790NZ", "G73968GN", "G74724QE", "G82830MN", "G83646BJ", "G85269DF", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G90734RJ", "G90787TS", "G92135MA", "G92406TI", "G94470IW", "G96091TT", "G98611JV", "G49108TO", "G02528FI", "G47702MW", "G77547TA" ], "uniprot_id": "Q13510" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "medium", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "Glycosylation may affect lysosomal targeting.", "mechanism": "Upregulated in MLIV plasma and mouse brain; involved in lysosomal function and protein processing.", "protein": "PLD3", "protein_enriched": { "function": "5'->3' exonuclease that hydrolyzes the phosphodiester bond of single-stranded DNA (ssDNA) and RNA molecules to form nucleoside 3'-monophosphates and 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotid", "gene_name": "PLD3", "glycan_count": 40, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11870QZ", "G14669DU", "G28681TP", "G45395BF", "G47644PP", "G47950XN", "G48414YA", "G55383ZG", "G70101JE", "G72291OX", "G74724QE", "G80920RR", "G82119TF", "G85269DF", "G92050GC", "G92275SC", "G95865ZB", "G05724UK", "G06110VR", "G14260UH", "G39188ZX", "G55220VL", "G64527OM", "G83633GK", "G27058EU", "G29545VG", "G31852PQ", "G36379GD", "G43223CG", "G57776ZS", "G62765YT", "G70232NH", "G71784JC", "G79666IR", "G83460ZZ", "G26330YA", "G40574BA", "G49108TO" ], "uniprot_id": "Q8IV08" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "medium", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Downregulated with age and disease severity; mediates neuroplasticity via reelin signaling.", "protein": "LRP8", "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "medium", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "N-glycosylation essential for secretion and function.", "mechanism": "Decreased with age and disease severity; required for vitamin B12 absorption and myelination.", "protein": "CBLIF", "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Mucolipidosis type IV (MLIV)", "glycan_involvement": "Heavily glycosylated; glycan chains mediate cell-cell interactions.", "mechanism": "Downregulated in MLIV plasma and mouse brain; involved in neuronal adhesion and myelination.", "protein": "CNTN2", "relationship_type": "biomarker", "source_pmcid": "PMC12141561" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation is essential for glycoprotein stability and function in platelet aggregation.", "mechanism": "Platelet glycoproteins mediate aggregation; their reduction or dysfunction is associated with low platelet count.", "protein": "Platelet glycoproteins (e.g., GPIIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "SERT is glycosylated, which affects its trafficking and function.", "mechanism": "SSRIs/SNRIs inhibit SERT on platelets, reducing serotonin uptake and impairing platelet aggregation, increasing risk of thrombocytopenia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "medium", "disease": "Bleeding risk", "glycan_involvement": "Glycosylation modulates glycoprotein interactions during clot formation.", "mechanism": "Reduced platelet glycoprotein function leads to impaired clot formation and increased bleeding risk.", "protein": "Platelet glycoproteins (e.g., GPIIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Depression", "glycan_involvement": "Glycosylation may affect SERT drug binding and cell surface expression.", "mechanism": "SERT is targeted by SSRIs/SNRIs to increase synaptic serotonin, treating depression.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12141916" }, { "confidence": "medium", "disease": "Thrombocytopenia (drug-induced)", "glycan_involvement": "Altered glycosylation may expose neoepitopes, triggering immune response.", "mechanism": "SSRIs/SNRIs may induce immune-mediated destruction or dysfunction of platelet glycoproteins.", "protein": "Platelet glycoproteins (e.g., GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Thrombocytopenia (sertraline-induced)", "glycan_involvement": "Glycosylation status may modulate SERT inhibition efficiency.", "mechanism": "Sertraline inhibits SERT on platelets, leading to decreased serotonin and impaired aggregation.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Thrombocytopenia (fluvoxamine-induced)", "glycan_involvement": "Glycosylation may affect SERT function and drug response.", "mechanism": "Fluvoxamine inhibits SERT on platelets, increasing risk of thrombocytopenia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Thrombocytopenia (paroxetine-induced)", "glycan_involvement": "Glycosylation may influence SERT's susceptibility to inhibition.", "mechanism": "Paroxetine inhibits SERT on platelets, leading to thrombocytopenia.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "medium", "disease": "Thrombocytopenia (escitalopram-induced)", "glycan_involvement": "Glycosylation differences may underlie variable drug effects.", "mechanism": "Escitalopram inhibits SERT, but risk of thrombocytopenia is lower than other SSRIs.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "medium", "disease": "Thrombocytopenia (duloxetine/venlafaxine-induced)", "glycan_involvement": "Glycosylation may modulate SERT inhibition and platelet effects.", "mechanism": "Duloxetine and venlafaxine inhibit SERT, but risk of thrombocytopenia is lower than paroxetine.", "protein": "Serotonin transporter (SERT, SLC6A4)", "relationship_type": "causal", "source_pmcid": "PMC12141916" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "PPAR\u03b3 is glycosylated; glycosylation may affect receptor stability and signaling.", "mechanism": "Downregulation of PPAR\u03b3 by 6PPD/6PPDQ disrupts lipid metabolism, leading to hepatic steatosis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "Glycosylation may modulate PPAR\u03b3's transcriptional activity.", "mechanism": "Reduced PPAR\u03b3 impairs anti-inflammatory signaling, promoting TNF-\u03b1/IL-6-mediated inflammation.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 indicates inflammatory response in liver after 6PPD/6PPDQ exposure.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141960" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "IL-6 glycosylation modulates stability and activity.", "mechanism": "Increased IL-6 reflects liver inflammation and progression to steatohepatitis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141960" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "FABP1 glycosylation may affect lipid binding and transport.", "mechanism": "Downregulation of FABP1 correlates with lipid accumulation and liver injury.", "protein": "FABP1", "protein_enriched": { "function": "Plays a role in lipoprotein-mediated cholesterol uptake in hepatocytes (PubMed:25732850). Binds cholesterol (PubMed:25732850). Binds free fatty acids and their coenzyme A derivatives, bilirubin, and s", "gene_name": "FABP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07148" }, "relationship_type": "biomarker", "source_pmcid": "PMC12141960" }, { "confidence": "medium", "disease": "Glucose dysregulation", "glycan_involvement": "Insulin glycosylation is essential for secretion and receptor interaction.", "mechanism": "Decreased insulin levels indicate impaired glucose metabolism after chemical exposure.", "protein": "INS (Insulin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12141960" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation may influence PPAR\u03b3 localization and mitochondrial signaling.", "mechanism": "PPAR\u03b3 downregulation impairs mitochondrial energy metabolism, reducing ATP production.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "medium", "disease": "Cholestatic liver disease", "glycan_involvement": "Glycosylation may affect PPAR\u03b3's interaction with bile acid pathway proteins.", "mechanism": "Disrupted PPAR\u03b3 signaling alters bile acid metabolism, contributing to cholestasis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "medium", "disease": "Oxidative stress injury", "glycan_involvement": "Glycosylation may modulate PPAR\u03b3's antioxidant gene regulation.", "mechanism": "PPAR\u03b3 suppression leads to reduced antioxidant defenses, increasing ROS and lipid peroxidation.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "low", "disease": "Neurobehavioral impairment", "glycan_involvement": "Glycosylation may impact PPAR\u03b3's neuroprotective functions.", "mechanism": "PPAR\u03b3 disruption affects energy homeostasis and behavior, leading to anxiety-like phenotypes.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12141960" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Defective O-glycosylation (galactose deficiency) in IgA1 hinge region.", "mechanism": "Mesangial deposition of Gd-IgA1 triggers immune complex formation and glomerular inflammation.", "protein": "Gd-IgA1 (Galactose-deficient IgA1)", "relationship_type": "causal", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Impaired O-glycosylation of IgA1.", "mechanism": "Genetic variants reduce galactosyltransferase activity, increasing Gd-IgA1 production.", "protein": "C1GALT1", "protein_enriched": { "function": "Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins (PubMed:11677243). Plays a centra", "gene_name": "C1GALT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NS00" }, "relationship_type": "causal", "source_pmcid": "PMC12142002" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Defective O-glycosylation in B cells.", "mechanism": "Loss-of-function mutations impair B-cell O-glycosylation and homing, contributing to IgAN.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Glycoprotein involved in complement regulation.", "mechanism": "Accumulation in glomeruli; genetic deficiency is protective.", "protein": "CFHR1", "protein_enriched": { "function": "Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with li", "gene_name": "CFHR1", "glycan_count": 36, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G10846ZT", "G11314AS", "G26330YA", "G27058EU", "G27947YN", "G28681TP", "G35029YA", "G36379GD", "G40574BA", "G45395BF", "G45504EY", "G48414YA", "G57317CE", "G57776ZU", "G57888GL", "G59626AS", "G70232NH", "G72747WU", "G72787SB", "G82830MN", "G92275SC", "G95865ZB", "G23719VF", "G23863VK", "G44215PV", "G46902YN", "G52527GH", "G65184UU", "G75983OB", "G84452RH" ], "uniprot_id": "Q03591" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Glycoprotein involved in complement regulation.", "mechanism": "Genetic deletion reduces disease risk.", "protein": "CFHR3", "protein_enriched": { "function": "Might be involved in complement regulation", "gene_name": "CFHR3", "glycan_count": 35, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G08918WF", "G10486CT", "G10846ZT", "G12341GU", "G25418HZ", "G26330YA", "G28681TP", "G33416PL", "G40574BA", "G45395BF", "G45504EY", "G48414YA", "G57317CE", "G57776ZU", "G59324HL", "G59626AS", "G61256FT", "G70232NH", "G70619PT", "G70888PK", "G92551JA", "G94470IW", "G95865ZB", "G15169WU", "G22310AV", "G39595FH", "G40834TG", "G47518TP", "G52527GH", "G56518TU", "G70441OD" ], "uniprot_id": "Q02985" }, "relationship_type": "protective", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Complement glycoprotein; activation linked to immune complex deposition.", "mechanism": "Glomerular C3 deposition correlates with disease severity.", "protein": "C3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142002" }, { "confidence": "medium", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Binds glycan structures, activates complement.", "mechanism": "Lectin pathway activation promotes glomerular injury.", "protein": "MBL (Mannose-binding lectin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Cytokine/glycoprotein modulating IgA production.", "mechanism": "Promotes B-cell differentiation and Gd-IgA1 overproduction.", "protein": "APRIL (TNFSF13)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA. Plays a role in the regulation of tumor cell growth. May be involved in monocyte/macrophage-mediated immunological processes", "gene_name": "TNFSF13", "glycan_count": 16, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G25451PN", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G57818FI", "G71146HJ", "G75983OB", "G83229XP", "G83460ZZ", "G84452RH", "G86795LJ" ], "uniprot_id": "O75888" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "Cytokine/glycoprotein modulating B-cell survival.", "mechanism": "Elevated BAFF drives B-cell proliferation and IgA production.", "protein": "BAFF (TNFSF13B)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell ", "gene_name": "TNFSF13B", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G28541PG", "G92135MA", "G49108TO" ], "uniprot_id": "Q9Y275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "IgA nephropathy (IgAN)", "glycan_involvement": "O-glycosylation status determines pathogenicity.", "mechanism": "Mesangial IgA1 deposition is diagnostic for IgAN.", "protein": "IgA1", "relationship_type": "biomarker", "source_pmcid": "PMC12142002" }, { "confidence": "high", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "CEA is a heavily glycosylated cell surface glycoprotein; altered glycosylation may affect tumor cell adhesion and immune evasion.", "mechanism": "CEA is overexpressed in CCA tissue compared to benign tissue, aiding diagnosis.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "high", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "No direct glycosylation involvement; p53 is not a glycoprotein.", "mechanism": "Mutant p53 accumulates in CCA cells, detectable by IHC, indicating tumor presence.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "high", "disease": "Benign pancreatobiliary tissue", "glycan_involvement": "Normal glycosylation patterns in benign tissue; altered in malignancy.", "mechanism": "Low CEA expression in benign tissue distinguishes it from CCA.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "low", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "CD56 is a glycoprotein, but its glycosylation status was not linked to CCA in this study.", "mechanism": "CD56 expression is not significantly associated with CCA diagnosis.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "low", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "SMAD4 is not a glycoprotein; no glycosylation involvement.", "mechanism": "Loss of SMAD4 expression observed in a minority of CCA cases, but not statistically significant.", "protein": "SMAD4", "protein_enriched": { "function": "In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 rele", "gene_name": "SMAD4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13485" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "medium", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "Altered glycosylation may affect CEA's immunogenicity and utility as a therapeutic target.", "mechanism": "CEA is used for monitoring treatment response and recurrence in CCA.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142014" }, { "confidence": "low", "disease": "Benign pancreatobiliary tissue", "glycan_involvement": "Glycosylation of CD56 may influence cell-cell interactions in benign tissue.", "mechanism": "CD56 may help differentiate non-neoplastic proliferation from neoplasia.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "medium", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "Aberrant glycosylation of CEA can promote malignant behavior.", "mechanism": "CEA overexpression may contribute to tumor cell adhesion and metastasis.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "causal", "source_pmcid": "PMC12142014" }, { "confidence": "high", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "No glycosylation involvement.", "mechanism": "p53 mutation leads to loss of cell cycle control, promoting tumorigenesis.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "causal", "source_pmcid": "PMC12142014" }, { "confidence": "high", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "Glycosylation is essential for CEA's stability and detection by antibodies.", "mechanism": "CEA tissue expression is significantly higher in CCA than in controls (79.6% vs. 11.1%).", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12142014" }, { "confidence": "high", "disease": "Advanced melanoma", "glycan_involvement": "PD-L1 glycosylation stabilizes protein and affects immune recognition.", "mechanism": "Upregulated on B cells, indicating regulatory immune response and associated with disease progression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Advanced melanoma", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Upregulated on B cells, promotes regulatory T cell expansion and immune suppression.", "protein": "TGF\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "medium", "disease": "Advanced melanoma", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Upregulated on plasmablasts and DN B cells, marks regulatory phenotype.", "protein": "CD95 (Fas)", "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Advanced melanoma", "glycan_involvement": "Fc glycosylation affects effector function and immune modulation.", "mechanism": "Serum enrichment indicates Th2-biased, immunosuppressive humoral response; predicts lower survival.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Advanced melanoma", "glycan_involvement": "Glycosylation required for receptor binding and stability.", "mechanism": "Serum enrichment in advanced disease; predicts lower survival but protective against irAE.", "protein": "IgE", "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Immune-related adverse events (irAE)", "glycan_involvement": "O-glycosylation in hinge region affects mucosal immunity.", "mechanism": "Higher baseline IgA predicts lack of irAE development during anti-PD-1 therapy.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Immune-related adverse events (irAE)", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Increased IL-10+ plasmablasts at baseline predict reduced irAE risk.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12142029" }, { "confidence": "medium", "disease": "Immune-related adverse events (irAE)", "glycan_involvement": "Tubulin glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against tubulins higher at baseline in patients without irAE; decrease during treatment.", "protein": "Tubulins (TUBB, TUBB4B, TUBB2A, TUBB4A)", "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "medium", "disease": "Immune-related adverse events (irAE)", "glycan_involvement": "Histone glycosylation is rare but may influence immune recognition.", "mechanism": "Autoantibodies against H4C1 increase during treatment in patients who develop toxicity.", "protein": "H4C1 (Histone H4)", "protein_enriched": { "function": "Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central r", "gene_name": "H4C1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P62805" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Extensive N-glycosylation required for TG function and immunogenicity.", "mechanism": "Autoantibodies against TG increase during treatment but do not correlate with endocrine toxicity onset.", "protein": "TG (Thyroglobulin)", "relationship_type": "biomarker", "source_pmcid": "PMC12142029" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Hb is a glycoprotein; EO forms adducts at N-terminal valine, potentially affecting glycan structure/function.", "mechanism": "Hemoglobin-bound ethylene oxide (HbEO) serves as a biomarker for EO exposure, which is inversely correlated with bone mineral density (BMD), a risk factor for osteoporosis.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142054" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation may influence HbEO adduct formation and immune response.", "mechanism": "Elevated HbEO levels are associated with increased risk of asthma, possibly mediated by systemic inflammation.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142054" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation status of Hb may modulate adduct formation and metabolic signaling.", "mechanism": "Higher HbEO levels linked to increased diabetes risk, potentially via oxidative stress and inflammation.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142054" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycan modifications may affect Hb interaction with EO and vascular function.", "mechanism": "HbEO levels are associated with hypertension risk, possibly through vascular oxidative stress.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142054" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Altered glycosylation may influence HbEO adduct stability and renal clearance.", "mechanism": "HbEO adducts are linked to 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In the endosome, the acidic pH induces conformational changes in the", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03522" }, "relationship_type": "therapeutic_agent_component", "source_pmcid": "PMC12142144" }, { "confidence": "medium", "disease": "General advanced solid tumors", "glycan_involvement": "Glycosylation may affect NY-ESO-1's immunogenicity and presentation.", "mechanism": "NY-ESO-1 expression in various solid tumors enables OVV-01 to enhance immune-mediated tumor killing.", "protein": "NY-ESO-1", "protein_enriched": { "function": "Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD)", "gene_name": "FAM8A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142144" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Integrin glycosylation affects ligand binding and receptor stability.", "mechanism": "Mediates inflammation, vascular leakage, and angiogenesis; inhibition reduces leukocyte recruitment, vascular permeability, and neovascularization.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Glycosylation modulates integrin function and cell surface expression.", "mechanism": "Promotes VEGF-induced angiogenesis and astrocyte apoptosis; inhibition reduces neovascularization and vascular leakage.", "protein": "Integrin \u03b1V\u03b25", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "N-glycosylation required for integrin folding and function.", "mechanism": "Activation increases vascular leakage and endothelial destabilization; inhibition improves junction integrity and reduces leakage.", "protein": "Integrin \u03b15\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates integrin activation and ligand binding.", "mechanism": "Mediates platelet aggregation and microthrombus formation; antagonists suppress aggregation in diabetic models.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Glycosylation affects integrin-ICAM-1 interaction.", "mechanism": "Enhances neutrophil adhesion to vascular wall via ICAM-1, promoting inflammation.", "protein": "Integrin \u03b1L\u03b22", "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Glycosylation influences integrin signaling.", "mechanism": "Mediates ANGPT2-induced pericyte apoptosis under hyperglycemia, contributing to early vascular leakage.", "protein": "Integrin \u03b13\u03b21", "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "medium", "disease": "Retinal Neovascularization", "glycan_involvement": "Glycosylation essential for integrin maturation.", "mechanism": "Required for normal retinal development; loss impairs vascular stability.", "protein": "Integrin \u03b28", "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "N-glycosylation modulates ICAM-1 binding affinity.", "mechanism": "Binds integrin \u03b1L\u03b22, facilitating leukocyte adhesion and transendothelial migration in retinal inflammation.", "protein": "ICAM-1 (CD54)", "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Glycosylation affects VCAM-1-integrin interactions.", "mechanism": "Interacts with integrins \u03b14\u03b21 and \u03b1V\u03b23, promoting lymphocyte migration and inflammation.", "protein": "VCAM-1 (CD106)", "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Glycosylation required for ANGPT2 secretion and receptor binding.", "mechanism": "Binds integrins \u03b13\u03b21, \u03b1V\u03b25, and \u03b15\u03b21, inducing pericyte and astrocyte apoptosis, increasing vascular leakage.", "protein": "ANGPT2", "protein_enriched": { "function": "Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling (PubMed:15284220, PubMed:19116766, PubMed:19223473, PubMed:9204896). Can induce tyrosine phosphorylation of TE", "gene_name": "ANGPT2", "glycan_count": 23, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G05962QB", "G30221QT", "G35541EV", "G62765YT", "G80479JV", "G81637OR", "G82443XX", "G93718GY", "G02815KT", "G10486CT", "G27058EU", "G41071NU", "G42124LM", "G45395BF", "G46691LC", "G68735SN", "G70619PT", "G90659AW", "G20956ZV", "G74724QE", "G34989PA", "G98611JV", "G49108TO" ], "uniprot_id": "O15123" }, "relationship_type": "causal", "source_pmcid": "PMC12142186" }, { "confidence": "high", "disease": "Myocardial Injury", "glycan_involvement": "Desmin is a glycoprotein; glycosylation may affect filament stability and cardiac pathology.", "mechanism": "Desmin-mediated myocardial damage is upregulated by high-dose L-Arg, leading to fibrosis and injury.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "causal", "source_pmcid": "PMC12142192" }, { "confidence": "high", "disease": "Oxidative Stress", "glycan_involvement": "Nrf2 glycosylation may regulate its stability and nuclear translocation.", "mechanism": "Nrf2 downregulation by high-dose L-Arg reduces antioxidant enzyme expression, increasing oxidative stress.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12142192" }, { "confidence": "medium", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation may modulate actin polymerization and fibrosis.", "mechanism": "Upregulation of \u03b1-SMA indicates fibrosis in myocardium after high-dose L-Arg.", "protein": "\u03b1-Smooth Muscle Actin (\u03b1-SMA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142192" }, { "confidence": "high", "disease": "Myocardial Injury", "glycan_involvement": "iNOS glycosylation can affect enzyme activity and localization.", "mechanism": "High-dose L-Arg increases iNOS expression, elevating NO and peroxynitrite, causing tissue damage.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC12142192" }, { "confidence": "medium", "disease": "Cardiac Dysfunction", "glycan_involvement": "eNOS glycosylation regulates enzyme activity and vascular function.", "mechanism": "High-dose L-Arg upregulates eNOS, increasing NO and contributing to oxidative/nitrosative stress.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal", "source_pmcid": "PMC12142192" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation affects catalase stability and activity.", "mechanism": "Catalase expression decreases with high-dose L-Arg, reducing ROS clearance.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12142192" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "SOD glycosylation modulates enzyme function.", "mechanism": "SOD levels decrease with high-dose L-Arg, impairing antioxidant defense.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12142192" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "Reduced glutathione peroxidase with high-dose L-Arg increases ROS.", "protein": "Glutathione Peroxidase", "relationship_type": "protective", "source_pmcid": "PMC12142192" }, { "confidence": "high", "disease": "Myocardial Injury", "glycan_involvement": "Glycosylation affects CK-MB serum stability and detection.", "mechanism": "CK-MB is elevated in serum after myocardial injury induced by high-dose L-Arg.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12142192" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL glycosylation modulates receptor binding and clearance.", "mechanism": "High-dose L-Arg increases LDL and oxidized LDL, promoting inflammation and cardiac injury.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12142192" }, { "confidence": "high", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Low HDL-C is a diagnostic criterion and risk marker for MetS.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "TG-rich lipoproteins contain glycosylated apolipoproteins affecting metabolism.", "mechanism": "Elevated TG is a diagnostic criterion and risk marker for MetS.", "protein": "TG", "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated ALT is associated with NAFLD and MetS risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect activity.", "mechanism": "ALT/AST ratio is used to assess liver dysfunction and NAFLD risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-atherogenic properties.", "mechanism": "High HDL-C is protective against cardiovascular disease.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of TG-rich lipoproteins influences clearance and vascular effects.", "mechanism": "High TG levels promote atherogenesis and cardiovascular risk.", "protein": "TG", "relationship_type": "causal", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects chronic glycemic control and diabetes risk.", "protein": "Glycosylated hemoglobin A1c (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "medium", "disease": "Metabolic syndrome (MetS)", "glycan_involvement": "TC is carried by glycoprotein-rich lipoproteins.", "mechanism": "TC/HDL-C ratio is a predictor of MetS and cardiovascular risk.", "protein": "TC", "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "LDL particles contain glycosylated apolipoproteins affecting receptor binding.", "mechanism": "High LDL-C is a major risk factor for atherosclerosis.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC12142194" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "Glycosylation may affect ALT secretion and stability.", "mechanism": "Elevated ALT is associated with liver fibrosis in NAFLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142194" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may affect CYP2J stability and localization.", "mechanism": "Upregulation increases EETs, which are anti-inflammatory and reduce fibrosis.", "protein": "CYP2J", "relationship_type": "protective", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Upregulation increases EETs, contributing to anti-inflammatory effects.", "protein": "CYP2B", "relationship_type": "protective", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may regulate CYP4A function.", "mechanism": "Upregulation increases 20-HETE, promoting inflammation and fibrosis.", "protein": "CYP4A", "relationship_type": "causal", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may affect CYP2E1 activity and ROS generation.", "mechanism": "Upregulation increases ROS and pro-inflammatory metabolites.", "protein": "CYP2E", "relationship_type": "causal", "source_pmcid": "PMC12142199" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation influences PLA2 secretion and activity.", "mechanism": "Upregulation increases AA substrate availability for anti-inflammatory metabolite production.", "protein": "PLA2 (Pla2g2e)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "Elevated in DN, drives renal inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation modulates IL-6 signaling.", "mechanism": "Elevated in DN, promotes inflammatory cell infiltration.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding.", "mechanism": "Elevated in DN, mediates glomerulosclerosis and injury.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12142199" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may regulate SOD secretion and activity.", "mechanism": "Decreased activity in DN, SZF restores antioxidant defense.", "protein": "SOD", "relationship_type": "protective", "source_pmcid": "PMC12142199" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Decreased activity in DN, SZF increases antioxidant capacity.", "protein": "GSH-Px", "relationship_type": "protective", "source_pmcid": "PMC12142199" }, { "confidence": "high", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "Direct cleavage of HS glycan chains from proteoglycans.", "mechanism": "Degrades heparan sulfate in the glomerular endothelial glycocalyx, leading to filtration barrier damage and proteinuria.", "protein": "Heparanase-1 (Hpa-1)", "relationship_type": "causal", "source_pmcid": "PMC12142201" }, { "confidence": "high", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "HS glycan chains are essential for barrier function.", "mechanism": "Maintains glomerular filtration barrier integrity; loss leads to increased permeability and albuminuria.", "protein": "Heparan sulfate proteoglycan (HS)", "relationship_type": "protective", "source_pmcid": "PMC12142201" }, { "confidence": "high", "disease": "Glomerular endothelial-mesenchymal transition (EndMT)", "glycan_involvement": "CD31 is a glycoprotein; glycosylation may affect cell-cell adhesion.", "mechanism": "Loss of CD31 marks transition from endothelial to mesenchymal phenotype in DKD.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142201" }, { "confidence": "high", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "PIK3R1 is glycosylated; glycosylation may modulate signaling.", "mechanism": "Regulates AKT signaling and heparanase expression; inhibition reduces EndMT and glycocalyx damage.", "protein": "PIK3R1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142201" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "AKT is glycosylated; glycosylation may affect kinase activity.", "mechanism": "Activated AKT promotes heparanase expression and EndMT.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12142201" }, { "confidence": "high", "disease": "Glomerular endothelial-mesenchymal transition (EndMT)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Upregulation indicates mesenchymal transition and fibrosis.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12142201" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "SRC is glycosylated; glycosylation may regulate kinase function.", "mechanism": "SRC kinase activity is implicated in DKD progression.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142201" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "STAT3 is glycosylated; glycosylation may affect transcriptional activity.", "mechanism": "STAT3 activation contributes to DKD pathogenesis.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142201" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "PIK3CA is glycosylated; glycosylation may modulate activity.", "mechanism": "Catalytic subunit of PI3K; involved in AKT activation and downstream effects.", "protein": "PIK3CA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142201" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "MAPK3 is glycosylated; glycosylation may affect signaling.", "mechanism": "MAPK3 signaling is involved in DKD progression.", "protein": "MAPK3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142201" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect; METTL3 modifies RNAs encoding glycoproteins, affecting their expression.", "mechanism": "METTL3 upregulation drives CRC progression via m6A-dependent stabilization of oncogenic mRNAs and ncRNAs, promoting proliferation, invasion, and metabolic reprogramming.", "protein": "METTL3", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, di", "gene_name": "METTL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U44" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Metastatic colorectal cancer", "glycan_involvement": "REG1\u03b1 is a secreted glycoprotein; m6A modification regulates its abundance.", "mechanism": "METTL3-mediated m6A modification increases REG1\u03b1 expression, activating Wnt/\u03b2-catenin pathway and driving metastasis.", "protein": "REG1\u03b1", "protein_enriched": { "function": "Has mitogenic activity and may be involved in maintaining the integrity of the gastric mucosal epithelium", "gene_name": "GKN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NS71" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "GLUT1 is a membrane glycoprotein; expression regulated by m6A-modified transcripts.", "mechanism": "METTL3 enhances m6A-dependent translation of GLUT1, increasing glucose uptake and fueling tumor growth.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Metastatic colorectal cancer", "glycan_involvement": "YAP1 is a glycoprotein; regulated via m6A-modified circRNA.", "mechanism": "METTL3 stabilizes circ1662, which binds YAP1, promoting its nuclear translocation and EMT/metastasis.", "protein": "YAP1", "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Chemoresistance in CRC", "glycan_involvement": "LDHA is glycosylated; m6A modification increases its expression.", "mechanism": "METTL3 stabilizes HIF-1\u03b1 and enhances LDHA translation via m6A, promoting glycolysis and drug resistance.", "protein": "LDHA", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHA", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G43223CG", "G57776ZS", "G84225JN", "G92406TI" ], "uniprot_id": "P00338" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Chemoresistance in CRC", "glycan_involvement": "TRAF5 is a glycoprotein; expression regulated by m6A.", "mechanism": "METTL3 stabilizes TRAF5 mRNA via m6A, conferring oxaliplatin resistance by promoting necrosis and evading apoptosis.", "protein": "TRAF5", "protein_enriched": { "function": "Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. M", "gene_name": "TRAF5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00463" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "medium", "disease": "Radioresistant colorectal cancer", "glycan_involvement": "LASP1 is glycosylated; regulated via m6A-modified circRNA.", "mechanism": "METTL3 elevates circ0124554, which sponges miR-1184, upregulating LASP1 and promoting radioresistance.", "protein": "LASP1", "protein_enriched": { "function": "Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport ", "gene_name": "LASP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q14847" }, "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "FASN is a glycoprotein; m6A modification increases its expression.", "mechanism": "METTL3 upregulates lncRNA POU6F2-AS1, recruiting YBX1 to activate FASN transcription, driving fatty acid synthesis and proliferation.", "protein": "FASN", "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "CCNE1 is glycosylated; expression regulated by m6A.", "mechanism": "METTL3 stabilizes CCNE1 mRNA via m6A, enhancing cyclin E1 levels and cell proliferation.", "protein": "CCNE1", "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "HK2 is glycosylated; m6A modification increases its expression.", "mechanism": "METTL3 stabilizes HK2 mRNA via m6A, promoting glycolysis and tumor growth.", "protein": "HK2", "relationship_type": "causal", "source_pmcid": "PMC12142237" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation affects stability and detection; glycoforms (AFP-L3) improve specificity.", "mechanism": "Elevated serum AFP correlates with tumor size, vascular invasion, metastasis, and poor prognosis; functions as immune suppressor and may promote drug resistance.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12142262" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Heparan sulfate chains modulate growth factor binding and signaling.", "mechanism": "Overexpressed in HCC, promotes tumor growth via Wnt signaling; targeted by antibodies and imaging agents.", "protein": "Glypican-3 (GPC3)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Heparan sulfate proteoglycan structure mediates cell-matrix interactions.", "mechanism": "Upregulated in HCC microvessels; correlates with tumor growth, metastasis, and poor recurrence-free survival.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142262" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Reduced APOB expression linked to poor prognosis, aggressive tumors, and immune evasion; regulates lipid metabolism and immune cell infiltration.", "protein": "Apolipoprotein B (APOB)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Putative glycosylation may affect stability and interactions (not directly shown).", "mechanism": "High SAMD13 expression correlates with advanced tumor grade, poor prognosis, and immune cell infiltration.", "protein": "SAMD13", "protein_enriched": { "function": "Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates", "gene_name": "ANKRD44", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N8A2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Upregulated in HCC; promotes proliferation, migration, and sorafenib resistance via Hippo pathway inhibition.", "protein": "MEX3A", "protein_enriched": { "function": "DNA-binding factor that regulates the expression of a subset of genes and plays a key role in tangential, radial, and lateral expansion of the brain neocortex. Regulates neural stem cells proliferatio", "gene_name": "TRNP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6NT89" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142262" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Detection often uses glycoprotein markers (e.g., mucin 1, EpCAM).", "mechanism": "CTC count correlates with metastasis, vascular invasion, recurrence, and poor survival; superior to AFP for recurrence prediction.", "protein": "Circulating Tumor Cells (CTCs)", "relationship_type": "biomarker", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Liver cirrhosis (LC)", "glycan_involvement": "N-glycosylation affects serum detection.", "mechanism": "Elevated AFP may indicate hepatic damage and regeneration in cirrhosis; less specific than in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Liver cirrhosis (LC)", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Low ApoB/ApoA1 ratio in CHB patients predicts higher risk of cirrhosis and HCC development.", "protein": "Apolipoprotein B (APOB)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12142262" }, { "confidence": "medium", "disease": "Liver cirrhosis (LC)", "glycan_involvement": "Heparan sulfate chains involved in cell signaling.", "mechanism": "Serum GPC3 less sensitive than AFP for distinguishing LC from HCC; combined use improves detection.", "protein": "Glypican-3 (GPC3)", "relationship_type": "biomarker (differential diagnosis)", "source_pmcid": "PMC12142262" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation status may affect stability and half-life, but not specifically discussed in SFTS context.", "mechanism": "Decreased serum albumin reflects liver dysfunction and increased vascular permeability in SFTS, associated with poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may modulate albumin's half-life and function, but not specifically addressed here.", "mechanism": "Low albumin is a prognostic marker for mortality in sepsis due to inflammation-induced capillary leakage and decreased synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation not specifically discussed.", "mechanism": "Low albumin is associated with increased risk of death in COVID-19, reflecting systemic inflammation and organ dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "medium", "disease": "Multiple organ dysfunction", "glycan_involvement": "Not specified.", "mechanism": "Decreased albumin indicates multi-organ involvement and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "LDH is not a glycoprotein.", "mechanism": "Elevated LDH reflects tissue and organ damage due to SFTSV infection and is an independent risk factor for mortality.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not applicable.", "mechanism": "High LDH is a predictor of fatal outcomes in COVID-19, reflecting systemic cell damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "medium", "disease": "Multiple organ dysfunction", "glycan_involvement": "Not specified.", "mechanism": "Low albumin is associated with increased vascular permeability and organ failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "low", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Not discussed.", "mechanism": "Albumin supplementation may be considered to improve plasma oncotic pressure in severe cases.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142283" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Not specified.", "mechanism": "Albumin is part of the composite LAU ratio, which is a strong predictor of mortality in SFTS.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "high", "disease": "Severe fever with thrombocytopenia syndrome (SFTS)", "glycan_involvement": "Not specified.", "mechanism": "Low albumin in combination with high LDH and BUN (LAU ratio) is associated with poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142283" }, { "confidence": "high", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "BCL-2 is a glycoprotein; glycosylation may affect stability and localization, but not directly discussed.", "mechanism": "Overexpression of BCL-2 promotes AML cell survival; inhibition by venetoclax restores apoptosis.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142305" }, { "confidence": "medium", "disease": "Chronic lymphocytic leukemia", "glycan_involvement": "BCL-2 glycosylation may modulate function; not directly discussed.", "mechanism": "BCL-2 overexpression supports leukemic cell survival; venetoclax targets BCL-2 to induce apoptosis.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142305" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "BCL-2 inhibition by venetoclax induces apoptosis in myeloma cells.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142305" }, { "confidence": "medium", "disease": "Mantle cell lymphoma", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "BCL-2 inhibition triggers apoptosis in lymphoma cells.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142305" }, { "confidence": "medium", "disease": "Tumor lysis syndrome (TLS)", "glycan_involvement": "No direct glycan involvement discussed.", "mechanism": "Rapid apoptosis of tumor cells by BCL-2 inhibition can precipitate TLS.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "causal", "source_pmcid": "PMC12142305" }, { "confidence": "low", "disease": "Cardiovascular events", "glycan_involvement": "No direct glycan involvement discussed.", "mechanism": "Venetoclax-induced BCL-2 inhibition may affect cardiac apoptosis and inflammation via NF-\u03baB/BCL-2 pathways.", "protein": "B-cell lymphoma 2 (BCL-2)", "relationship_type": "causal", "source_pmcid": "PMC12142305" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CD34 is a heavily glycosylated sialomucin; glycosylation is essential for its function and detection.", "mechanism": "CD34 expression marks LSEC capillarisation, appearing early in MASLD.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation of CD34 affects its role in endothelial phenotype and capillarisation.", "mechanism": "Increased CD34 staining correlates with severity of MASH and is linked to progression to fibrosis.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation of CD34 modulates cell-cell interactions in fibrogenesis.", "mechanism": "LSEC capillarisation (CD34+) is strongly associated with liver fibrosis development.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142333" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation may influence immune cell recruitment via CD34.", "mechanism": "CD34 staining correlates with liver inflammation, though less strongly than with fibrosis.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "Isolated steatosis (MASL)", "glycan_involvement": "Glycosylation is required for CD34 detection and function.", "mechanism": "Lobular CD34 staining is increased in MASL, indicating early endothelial changes.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Therapeutic modulation may affect glycosylation status of CD34.", "mechanism": "Lanifibranor treatment reduces CD34+ LSEC capillarisation, improving endothelial phenotype.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142333" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Cytokeratin 18 is glycosylated; glycan fragments may be released during cell death.", "mechanism": "Serum cytokeratin 18 M65 fragments correlate with CD34 lobular staining and cell death in MASH.", "protein": "Cytokeratin 18", "protein_enriched": { "function": "Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to th", "gene_name": "KRT18", "glycan_count": 6, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G57321FI", "G83646BJ", "G47012YE", "G62765YT", "G64527OM" ], "uniprot_id": "P05783" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142333" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Collagen-1 is glycosylated, affecting its assembly and fibrotic matrix formation.", "mechanism": "Collagen-1 deposition is absent in early MASLD/MASH but increases with fibrosis.", "protein": "Collagen-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation is essential for CD34's endothelial function.", "mechanism": "CD34+ LSEC capillarisation is present in preclinical models of early MASLD.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Potential modulation of glycosylation status with therapy.", "mechanism": "Lanifibranor dose-dependently reduces LSEC capillarisation (CD34+) in periportal zone.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142333" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation affects apoB structure and LDL particle stability.", "mechanism": "Elevated apoB reflects increased LDL particles, a key marker for dyslipidemia.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "High apoB levels are associated with increased risk of CVD due to atherogenic LDL particles.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation influences HDL formation and cholesterol efflux.", "mechanism": "apoA1 is the main protein of HDL; higher levels are protective against dyslipidemia.", "protein": "Apolipoprotein A1 (apoA1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12142697" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation impacts receptor interactions and lipid transport.", "mechanism": "apoE mediates lipoprotein clearance; variants affect lipid levels.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "O-glycosylation of apo(a) affects Lp(a) structure and function.", "mechanism": "Elevated Lp(a) is an independent risk factor for CVD.", "protein": "Lipoprotein (a)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "LDL particles contain glycosylated apoB; glycosylation affects clearance.", "mechanism": "High LDL-C promotes atherosclerosis and ASCVD.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation of apoA1 and other HDL proteins modulates function.", "mechanism": "High HDL-C is protective against CVD.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "N-glycosylation affects LDL assembly and metabolism.", "mechanism": "apoB is essential for LDL formation; elevated levels drive hypercholesterolemia.", "protein": "Apolipoprotein B (apoB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates anti-atherogenic functions.", "mechanism": "apoA1 promotes reverse cholesterol transport, reducing CVD risk.", "protein": "Apolipoprotein A1 (apoA1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12142697" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects receptor binding and lipoprotein clearance.", "mechanism": "apoE variants influence CVD risk via lipid metabolism.", "protein": "Apolipoprotein E (apoE)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12142697" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "IA-2 is a glycoprotein; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Autoantibodies to IA-2 are markers of autoimmune destruction of pancreatic beta cells.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "medium", "disease": "COVID-19-associated dysglycemia", "glycan_involvement": "Glycosylation may modulate immune recognition of IA-2 during infection.", "mechanism": "Transient IA-2 autoantibody positivity observed during acute COVID-19 infection, suggesting virus-triggered autoimmunity.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "high", "disease": "MODY6 (NEUROD1-MODY)", "glycan_involvement": "Not directly glycosylated; no glycan involvement.", "mechanism": "Heterozygous NEUROD1 mutations impair insulin gene transcription and beta cell function.", "protein": "NEUROD1", "relationship_type": "causal", "source_pmcid": "PMC12142834" }, { "confidence": "medium", "disease": "MODY6 (NEUROD1-MODY)", "glycan_involvement": "Glycosylation may influence IA-2 immunogenicity.", "mechanism": "Transient IA-2 autoantibody positivity can occur in MODY6 during immune activation (e.g., COVID-19).", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "low", "disease": "Microalbuminuria", "glycan_involvement": "Glycosylation status may affect IA-2's role in autoimmunity.", "mechanism": "Autoimmunity to IA-2 may be associated with beta cell dysfunction, contributing to hyperglycemia and renal complications.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Not applicable.", "mechanism": "NEUROD1 is expressed in neurons; mutation may contribute to neurodevelopmental phenotypes.", "protein": "NEUROD1", "relationship_type": "causal (possible)", "source_pmcid": "PMC12142834" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may affect epitope presentation.", "mechanism": "Targeted immune modulation against IA-2 autoimmunity is a potential therapeutic strategy.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142834" }, { "confidence": "medium", "disease": "COVID-19-associated dysglycemia", "glycan_involvement": "Glycosylation may influence immune response.", "mechanism": "IA-2 autoantibody positivity may indicate transient beta cell autoimmunity post-COVID-19.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Not applicable.", "mechanism": "Certain NEUROD1 polymorphisms may increase susceptibility to autoimmune diabetes.", "protein": "NEUROD1", "relationship_type": "risk_modifier", "source_pmcid": "PMC12142834" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "IA-2 autoantibodies are used in staging and diagnosis of type 1 diabetes.", "protein": "Islet-antigen 2 (IA-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12142834" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CEA is a heavily glycosylated protein; altered glycosylation affects its serum levels and detection.", "mechanism": "Elevated preoperative CEA levels are associated with higher risk of peritoneal metastasis and recurrence in CRC.", "protein": "Carcinoembryonic Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142866" }, { "confidence": "high", "disease": "Peritoneal metastasis", "glycan_involvement": "Glycosylation modulates CEA's stability and immune recognition.", "mechanism": "High CEA levels (\u226510 ng/ml) are a risk factor for postoperative peritoneal metastasis in CRC.", "protein": "Carcinoembryonic Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142866" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "CA-199 is a glycan epitope (sialylated Lewis antigen) on glycoproteins/lipids.", "mechanism": "CA-199 is used as a serum biomarker for CRC recurrence and metastasis monitoring.", "protein": "CA-199 (Sialyl-Lewis^a antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12142866" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Altered glycosylation may enhance CEA's metastatic potential.", "mechanism": "Elevated CEA is associated with increased risk of liver metastasis in CRC.", "protein": "Carcinoembryonic Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142866" }, { "confidence": "medium", "disease": "Liver metastasis", "glycan_involvement": "Sialyl-Lewis^a is a glycan determinant involved in cell adhesion and metastasis.", "mechanism": "CA-199 is monitored for detection of liver metastasis in CRC patients.", "protein": "CA-199 (Sialyl-Lewis^a antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12142866" }, { "confidence": "medium", "disease": "Major depressive disorder", "glycan_involvement": "Albumin glycosylation may affect its binding and transport capacity for drugs.", "mechanism": "Lower albumin levels in children/adolescents are associated with altered sertraline pharmacokinetics, potentially reflecting nutritional status and disease severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "high", "disease": "Major depressive disorder", "glycan_involvement": "hsCRP glycosylation is essential for its stability and function as an inflammatory marker.", "mechanism": "U-shaped correlation between hsCRP levels and sertraline concentrations in children/adolescents suggests inflammation modulates drug metabolism.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Glycosylation of AST may affect its secretion and stability.", "mechanism": "Elevated AST levels correlate with higher sertraline concentrations, indicating impaired hepatic metabolism.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "high", "disease": "Inflammatory state", "glycan_involvement": "Glycosylation is required for hsCRP's function and clearance.", "mechanism": "hsCRP is a marker of systemic inflammation, which can induce phenoconversion of drug-metabolizing enzymes.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "medium", "disease": "Renal disease", "glycan_involvement": "Glycosylation state may influence albumin's renal filtration and loss.", "mechanism": "Albumin levels are altered in renal disease, potentially affecting drug binding and pharmacokinetics.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "medium", "disease": "Inflammatory state", "glycan_involvement": "Surface glycoproteins mediate neutrophil activation and trafficking.", "mechanism": "Neutrophil count inversely correlates with sertraline concentration in children/adolescents, reflecting inflammation's impact on drug metabolism.", "protein": "Neutrophil (surface glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "medium", "disease": "Behavioral and emotional disorders (child/adolescent)", "glycan_involvement": "Glycosylation affects hsCRP's immunological activity.", "mechanism": "Elevated hsCRP may indicate inflammatory subtypes of psychiatric disorders, affecting drug response.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "low", "disease": "Anxiety disorders", "glycan_involvement": "Glycosylation modulates albumin's drug-binding properties.", "mechanism": "Albumin levels may reflect nutritional and inflammatory status in anxiety disorders, impacting drug pharmacokinetics.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "medium", "disease": "Major depressive disorder", "glycan_involvement": "Glycosylation may influence AST's serum half-life.", "mechanism": "AST elevation may signal hepatic involvement in depressive patients, affecting drug metabolism.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "low", "disease": "Anxiety disorders", "glycan_involvement": "Glycosylation is necessary for hsCRP's function as an acute-phase reactant.", "mechanism": "hsCRP elevation may indicate inflammatory comorbidity in anxiety disorders, influencing drug metabolism.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12142871" }, { "confidence": "high", "disease": "Brucellosis", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP is elevated in response to inflammation caused by Brucella infection.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "high", "disease": "Brucellosis", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "Brucella-specific IgG detected by serology indicates infection.", "protein": "Immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "medium", "disease": "Brucellosis", "glycan_involvement": "Glycosylation influences PCT secretion and stability.", "mechanism": "Elevated PCT reflects systemic bacterial infection.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic hyperglycemia, which predisposes to infection.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "medium", "disease": "Liver abscess", "glycan_involvement": "N-glycosylation affects albumin half-life.", "mechanism": "Low albumin may indicate liver dysfunction due to abscess.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "medium", "disease": "Brucellosis", "glycan_involvement": "Bacterial glycosylation modulates antigenicity.", "mechanism": "Brucella Omp glycoproteins mediate host cell invasion and immune evasion.", "protein": "Brucella Omp (outer membrane proteins)", "relationship_type": "causal", "source_pmcid": "PMC12142888" }, { "confidence": "high", "disease": "Brucellosis", "glycan_involvement": "Glycan structure determines antigenicity.", "mechanism": "Glycoprotein antigen used for serological diagnosis.", "protein": "Rose Bengal Plate Test antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "high", "disease": "Brucellosis", "glycan_involvement": "Glycan epitopes drive agglutination.", "mechanism": "Glycoprotein antigen used for confirmatory serological diagnosis.", "protein": "Standard Agglutination Test antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Fc glycosylation modulates immune response.", "mechanism": "IgG response to HBV antigens indicates chronic infection.", "protein": "Immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Altered glycosylation in liver disease.", "mechanism": "Low albumin reflects chronic liver damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142888" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "PLCD4 is a putative glycoprotein; glycosylation may affect stability or localization, but not directly studied here.", "mechanism": "PLCD4 inhibits CRC cell migration, invasion, and tumor growth; its expression is downregulated in CRC.", "protein": "PLCD4", "protein_enriched": { "function": "Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the gly", "gene_name": "AGPAT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRZ5" }, "relationship_type": "tumor suppressor/therapeutic_target", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "CRC immune resistance", "glycan_involvement": "Potential glycosylation may modulate immune interactions; not directly addressed.", "mechanism": "PLCD4 expression correlates with increased immune and stromal infiltration, reducing tumor purity.", "protein": "PLCD4", "protein_enriched": { "function": "Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the gly", "gene_name": "AGPAT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRZ5" }, "relationship_type": "protective", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "IFNGR1 is a glycoprotein; glycosylation is essential for receptor function but not specifically studied here.", "mechanism": "Upregulation of IFNGR1 reverses IFN-\u03b3 resistance in CRC cells, enhancing immune response.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation regulates immune checkpoint function, but not specifically analyzed here.", "mechanism": "PD-L1 expression is increased by lncRNA 60967.1, enhancing response to anti\u2013PD-1 therapy.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Putative glycosylation may affect biomarker detectability.", "mechanism": "Low PLCD4 expression is associated with poor prognosis and advanced CRC.", "protein": "PLCD4", "protein_enriched": { "function": "Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the gly", "gene_name": "AGPAT4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRZ5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "CRC immune resistance", "glycan_involvement": "Glycosylation required for IFNGR1 function; not directly studied.", "mechanism": "Increased IFNGR1 restores IFN-\u03b3 sensitivity, promoting apoptosis in CRC cells.", "protein": "IFNGR1", "protein_enriched": { "function": "Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:", "gene_name": "IFNGR1", "glycan_count": 13, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G07483YN", "G09724ZC", "G14260UH", "G53168IY", "G62765YT", "G70101JE", "G82348BZ", "G83460ZZ", "G40379SA", "G23453IV", "G66538GV", "G74724QE", "G94854LT" ], "uniprot_id": "P15260" }, "relationship_type": "protective", "source_pmcid": "PMC12142938" }, { "confidence": "medium", "disease": "CRC immune resistance", "glycan_involvement": "Glycosylation modulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 upregulation by lncRNA 60967.1 sensitizes tumors to anti\u2013PD-1 therapy.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12142938" }, { "confidence": "high", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "Loss of heparan sulfate glycosaminoglycan chains from syndecan-1 disrupts glycocalyx integrity.", "mechanism": "Elevated syndecan-1 indicates glycocalyx degradation, associated with endothelial injury and DCI.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142988" }, { "confidence": "high", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "Glycosylation regulates VWF multimerization and function in platelet binding.", "mechanism": "Elevated VWF promotes platelet adhesion and microthrombosis, contributing to DCI.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "high", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "Glycosylation affects ADAMTS-13 secretion and activity.", "mechanism": "ADAMTS-13 cleaves VWF, reducing thrombogenicity; deficiency linked to increased DCI risk.", "protein": "ADAMTS-13", "relationship_type": "protective", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "N-glycosylation modulates VCAM-1 cell surface expression and leukocyte binding.", "mechanism": "Elevated VCAM-1 reflects endothelial activation and neuro-inflammation in DCI.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "N-glycosylation required for ICAM-1 function in cell adhesion.", "mechanism": "Upregulated ICAM-1 promotes leukocyte adhesion and neuro-inflammation, contributing to DCI.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "high", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "Glycosylation essential for P-selectin ligand binding.", "mechanism": "P-selectin mediates platelet-leukocyte-endothelial interactions, driving thrombo-inflammation in DCI.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "O-glycosylation of PSGL-1 required for P-selectin binding.", "mechanism": "Elevated PSGL-1 expression correlates with DCI and poor outcomes.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "biomarker", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "Glycosylation modulates E-selectin ligand interactions.", "mechanism": "E-selectin upregulation facilitates leukocyte recruitment and neuro-inflammation in DCI.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Cerebral Edema", "glycan_involvement": "Glycosylation affects AQP4 membrane localization and water channel function.", "mechanism": "AQP4 channel dysfunction exacerbates cytotoxic edema after aSAH.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "medium", "disease": "Delayed Cerebral Ischemia (DCI)", "glycan_involvement": "N-glycosylation influences MMP-9 secretion and activity.", "mechanism": "MMP-9 degrades glycocalyx and extracellular matrix, increasing BBB permeability and DCI risk.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12142988" }, { "confidence": "high", "disease": "Porphyria cutanea tarda (PCT)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Deficiency or inhibition of UROD leads to accumulation of uroporphyrins, causing PCT.", "protein": "Uroporphyrinogen decarboxylase (UROD)", "protein_enriched": { "function": "Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway (PubMed:1106", "gene_name": "UROD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06132" }, "relationship_type": "causal", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "ANA are glycoproteins; glycosylation may affect antigenicity.", "mechanism": "Presence of ANA is a diagnostic marker for SLE.", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation of IgG affects pathogenicity and clearance.", "mechanism": "Anti-dsDNA antibodies are specific markers for SLE and correlate with disease activity.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for function.", "mechanism": "Low C3 levels indicate complement consumption in active SLE.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "C4 is a glycoprotein; glycosylation is required for stability.", "mechanism": "Low C4 levels are associated with SLE activity.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Antibody glycosylation may modulate immune complex formation.", "mechanism": "Anti-RNP antibodies are found in SLE and mixed connective tissue disease.", "protein": "Anti-RNP antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered IgG glycosylation (e.g., hypogalactosylation) is linked to SLE activity.", "mechanism": "IgG autoantibodies are central to SLE pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "\u03b22-glycoprotein I is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "Associated with antiphospholipid syndrome in SLE.", "protein": "Anti-\u03b22-glycoprotein I antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "low", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Genetic loci for UROD and SLE are both on chromosome 1q41\u2013q42, suggesting possible shared susceptibility.", "protein": "Uroporphyrinogen decarboxylase (UROD)", "protein_enriched": { "function": "Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway (PubMed:1106", "gene_name": "UROD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06132" }, "relationship_type": "genetic association", "source_pmcid": "PMC12143034" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "IgM is highly glycosylated; glycosylation affects function.", "mechanism": "IgM autoantibodies are present in SLE and may have protective roles.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143034" }, { "confidence": "high", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "HDL particles are glycosylated, affecting their function and interaction with cell receptors.", "mechanism": "Higher HDL-C levels are associated with increased insulin sensitivity and improved \u03b2-cell function, reducing T2D risk.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "Glycosylation modulates lipoprotein metabolism and receptor binding.", "mechanism": "Elevated TG levels impair glucose oxidation/utilization and promote insulin resistance, increasing T2D risk.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation status influences HDL function and anti-inflammatory properties.", "mechanism": "Low HDL-C is linked to decreased insulin sensitivity and impaired \u03b2-cell function.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects TG-rich lipoprotein clearance and receptor interactions.", "mechanism": "High TG levels compete with glucose for cellular entry, promoting insulin resistance.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin forms HbA1c.", "mechanism": "HbA1c reflects chronic hyperglycemia and is used for T2D diagnosis.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143047" }, { "confidence": "medium", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Elevated GGT is associated with increased risk of T2D.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143047" }, { "confidence": "medium", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "ALT is glycosylated, which may affect its secretion and activity.", "mechanism": "Higher ALT levels are linked to increased T2D risk, reflecting liver dysfunction.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143047" }, { "confidence": "medium", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "AST glycosylation may influence its serum levels.", "mechanism": "Elevated AST is associated with increased T2D risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Atherosclerotic dyslipidemia", "glycan_involvement": "Glycosylation modulates HDL particle function.", "mechanism": "HDL-C reduces atherogenic risk by promoting cholesterol efflux and anti-inflammatory effects.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Atherosclerotic dyslipidemia", "glycan_involvement": "Glycosylation affects lipoprotein metabolism and atherogenicity.", "mechanism": "High TG promotes atherogenesis and dyslipidemia.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12143047" }, { "confidence": "high", "disease": "Malignant Ascites", "glycan_involvement": "VEGFA is a glycosylated protein; glycosylation affects its stability and secretion.", "mechanism": "VEGFA promotes angiogenesis and increases vascular permeability, leading to accumulation of ascitic fluid in peritoneal metastasis.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143064" }, { "confidence": "high", "disease": "Gastric Cancer with Peritoneal Metastasis", "glycan_involvement": "Glycosylation modulates VEGFA bioactivity and receptor binding.", "mechanism": "High VEGFA levels in ascites correlate with ascites volume and poor prognosis in GCPM.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143064" }, { "confidence": "high", "disease": "Gastric Cancer with Peritoneal Metastasis", "glycan_involvement": "Bevacizumab is a glycosylated monoclonal antibody; glycosylation affects its pharmacokinetics and efficacy.", "mechanism": "Bevacizumab binds VEGFA, inhibiting angiogenesis and reducing ascites formation.", "protein": "Bevacizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "PD-1 is N-glycosylated; glycosylation regulates its cell surface expression and ligand binding.", "mechanism": "PD-1 inhibitors (e.g., sintilimab) block immune checkpoint, enhancing anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "PD-L1 glycosylation stabilizes protein and modulates immune evasion.", "mechanism": "PD-L1 expression on tumor cells suppresses immune response; blockade improves survival.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "Gastric Cancer with Peritoneal Metastasis", "glycan_involvement": "Albumin is glycosylated; glycosylation affects drug binding and distribution.", "mechanism": "Albumin-bound formulation increases drug delivery to peritoneal cavity and reduces hypersensitivity.", "protein": "Albumin-bound Paclitaxel", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Ramucirumab is a glycosylated antibody; glycosylation impacts efficacy.", "mechanism": "Ramucirumab targets VEGFR2, inhibiting angiogenesis in advanced GC.", "protein": "Ramucirumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "HER2-positive Gastric Cancer", "glycan_involvement": "HER2 is glycosylated; glycosylation affects receptor dimerization and signaling.", "mechanism": "HER2 overexpression defines a GC subtype; targeted therapies improve outcomes.", "protein": "HER2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation modulates VEGFA activity.", "mechanism": "VEGFA-driven angiogenesis and ascites formation targeted by bevacizumab.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143064" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Antibody glycosylation affects clinical efficacy.", "mechanism": "Bevacizumab inhibits VEGFA, reducing tumor angiogenesis.", "protein": "Bevacizumab", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12143064" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "O-glycosylation affects GLP-1 stability and secretion.", "mechanism": "SCFAs stimulate GLP-1 secretion via GPCRs, influencing insulin secretion and glucose homeostasis.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "O-glycosylation modulates PYY secretion and activity.", "mechanism": "SCFAs stimulate PYY secretion, modulating satiety and glucose metabolism.", "protein": "PYY", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Increased intestinal permeability ('leaky gut')", "glycan_involvement": "N-glycosylation affects LBP stability and function.", "mechanism": "LBP levels reflect gut barrier dysfunction, which is associated with T2D risk.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Increased intestinal permeability ('leaky gut')", "glycan_involvement": "N-glycosylation modulates zonulin secretion and activity.", "mechanism": "Zonulin regulates tight junctions; elevated in T2D, indicating barrier dysfunction.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "O-glycosylation influences leptin secretion and receptor binding.", "mechanism": "SCFAs regulate leptin expression, impacting insulin sensitivity and energy balance.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "O-glycosylation is essential for adiponectin multimerization and function.", "mechanism": "SCFAs upregulate adiponectin, improving insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "O-glycosylation affects resistin secretion.", "mechanism": "SCFAs modulate resistin expression, influencing inflammation and insulin resistance.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "N-glycosylation affects LBP's role in immune response.", "mechanism": "LBP is elevated in T2D, reflecting metabolic endotoxemia and inflammation.", "protein": "LBP", "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "N-glycosylation modulates zonulin's effect on tight junctions.", "mechanism": "Elevated zonulin in T2D indicates increased gut permeability.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143092" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation affects GLP-1 half-life.", "mechanism": "GLP-1 secretion (stimulated by SCFAs) regulates appetite and body weight.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143092" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLUT4 is N-glycosylated, affecting trafficking and function.", "mechanism": "Reduced GLUT4 expression impairs glucose uptake; mAPS increases GLUT4, improving glycemic control.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143329" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "TLR4 N-glycosylation is essential for LPS recognition and signaling.", "mechanism": "TLR4 activation by LPS triggers NF-\u03baB-mediated inflammation, contributing to insulin resistance.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12143329" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "Glycosylation modulates NF-\u03baB nuclear translocation and activity.", "mechanism": "NF-\u03baB activation increases pro-inflammatory cytokines, promoting hepatic inflammation in T2DM.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12143329" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "PI3K subunits are glycosylated, influencing stability and localization.", "mechanism": "PI3K activation is required for insulin signaling; mAPS restores PI3K levels, improving insulin sensitivity.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143329" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "AKT glycosylation affects kinase activity.", "mechanism": "AKT phosphorylation is reduced in T2DM; mAPS increases p-AKT, enhancing insulin signaling.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143329" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Occludin is N-glycosylated, critical for tight junction assembly.", "mechanism": "Reduced Occludin expression increases gut permeability; mAPS restores Occludin, improving barrier integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143329" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "ZO-1 glycosylation modulates tight junction stability.", "mechanism": "ZO-1 downregulation correlates with increased permeability and inflammation in T2DM; mAPS upregulates ZO-1.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143329" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated, affecting secretion and activity.", "mechanism": "Elevated IL-1\u03b2 reflects hepatic and systemic inflammation in T2DM; mAPS reduces IL-1\u03b2 levels.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143329" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation influences receptor binding.", "mechanism": "Increased TNF-\u03b1 promotes insulin resistance and hepatic inflammation; mAPS lowers TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143329" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "IRS glycosylation modulates insulin receptor interaction.", "mechanism": "IRS phosphorylation is key for insulin signaling; no significant change with mAPS in this study.", "protein": "IRS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143329" }, { "confidence": "high", "disease": "DMED", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Promotes inflammatory response in testicular tissue, contributing to erectile dysfunction.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "high", "disease": "DMED", "glycan_involvement": "IL-1\u03b2 is glycosylated, which modulates its activity and secretion.", "mechanism": "Induces inflammation in testicular tissue, leading to tissue damage and reduced testosterone.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "high", "disease": "DMED", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation influences receptor binding and bioactivity.", "mechanism": "Drives inflammatory cascade in testicular tissue, impairing erectile function.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "high", "disease": "DMED", "glycan_involvement": "NF-\u03baB activity is modulated by upstream glycoprotein cytokines.", "mechanism": "Central regulator of inflammatory gene expression; inhibition reduces inflammation and tissue damage.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143331" }, { "confidence": "medium", "disease": "DMED", "glycan_involvement": "Regulation is influenced by glycoprotein cytokine signaling.", "mechanism": "Inhibits NF-\u03baB; altered expression affects inflammatory signaling.", "protein": "I\u03baB-\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143331" }, { "confidence": "medium", "disease": "DMED", "glycan_involvement": "EGFR is heavily N-glycosylated, affecting ligand binding and signaling.", "mechanism": "Involved in tissue repair and fibrosis; dysregulation contributes to penile tissue damage.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "medium", "disease": "DMED", "glycan_involvement": "MAPK3 function is modulated by upstream glycoprotein signaling.", "mechanism": "Mediates inflammatory and stress responses in penile/testicular tissue.", "protein": "MAPK3", "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "medium", "disease": "Testicular inflammation/damage", "glycan_involvement": "Activation is downstream of glycoprotein cytokine signaling.", "mechanism": "Executes apoptosis in testicular cells during inflammation.", "protein": "CASP3", "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "medium", "disease": "Penile tissue fibrosis", "glycan_involvement": "Glycosylation modulates IL-6 stability and profibrotic activity.", "mechanism": "Promotes extracellular matrix deposition and fibrosis in penile tissue.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12143331" }, { "confidence": "high", "disease": "DMED", "glycan_involvement": "Testosterone is not a glycoprotein, but its regulation is affected by glycoprotein cytokines.", "mechanism": "Higher T levels improve erectile function; inflammation reduces T production.", "protein": "Testosterone (T)", "protein_enriched": { "function": "Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine", "gene_name": "TFF1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P04155" }, "relationship_type": "protective", "source_pmcid": "PMC12143331" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency (AATD)", "glycan_involvement": "AAT is a glycoprotein; glycosylation affects folding and secretion.", "mechanism": "Mutations in SERPINA1 gene lead to reduced AAT secretion and accumulation in hepatocytes.", "protein": "Alpha-1 antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12143362" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may modulate polymer formation and ER retention.", "mechanism": "Z-AAT polymerizes and accumulates in hepatocytes, causing proteotoxic stress and cirrhosis.", "protein": "Z-alpha-1 antitrypsin (Z-AAT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143362" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation status may affect Z-AAT clearance and toxicity.", "mechanism": "Chronic liver injury from Z-AAT accumulation increases risk of liver cancer.", "protein": "Z-alpha-1 antitrypsin (Z-AAT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143362" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects stability and serum levels.", "mechanism": "Elevated GGT correlates with advanced fibrosis and predicts adverse liver outcomes in AATD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "AST is glycosylated; glycosylation may affect serum half-life.", "mechanism": "Elevated AST is associated with liver fibrosis progression in AATD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function.", "mechanism": "Low platelet count (due to portal hypertension) is used in APRI and FIB-4 scores for fibrosis staging.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects plasma stability and function.", "mechanism": "Included in HepaScore panel for advanced fibrosis detection.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation (deficient sialylation) is the basis of the biomarker.", "mechanism": "Used as a surrogate marker for alcohol-induced liver injury in AATD.", "protein": "Carbohydrate-deficient transferrin", "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "high", "disease": "Neonatal cholestasis", "glycan_involvement": "Glycosylation may influence ER retention and secretion.", "mechanism": "Z-AAT retention in hepatocytes causes cholestatic liver disease in infants.", "protein": "Z-alpha-1 antitrypsin (Z-AAT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12143362" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect peptide stability and detection.", "mechanism": "Potential future biomarker for liver fibrosis in AATD.", "protein": "Procollagen type III N-terminal peptide (pro-C3)", "relationship_type": "biomarker", "source_pmcid": "PMC12143362" }, { "confidence": "high", "disease": "Neurodegenerative Disorders (general)", "glycan_involvement": "Polysialylation of NCAM1 is critical for neuronal migration and plasticity.", "mechanism": "NCAM1 expression marks neuronal identity and survival in reprogrammed neurons; used to track graft integration.", "protein": "NCAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation affects TH stability and localization.", "mechanism": "TH+ neurons indicate successful dopaminergic neuron generation, relevant for PD modeling and therapy.", "protein": "TH", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12143395" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "N-glycosylation regulates DAT trafficking and function.", "mechanism": "DAT expression confirms dopaminergic neuron identity; loss of DAT is a hallmark of PD.", "protein": "DAT/SLC6A3", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation modulates VMAT2 stability and vesicular targeting.", "mechanism": "VMAT2+ neurons indicate functional dopamine packaging and release, relevant for PD.", "protein": "VMAT2/SLC18A2", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation may affect ALDH1A1 enzymatic activity.", "mechanism": "ALDH1A1 marks a subset of DA neurons with increased resistance to degeneration in PD.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation influences GIRK2 channel function.", "mechanism": "GIRK2 identifies A9 DA neuron subtype, selectively lost in PD.", "protein": "GIRK2 (KCNJ6)", "protein_enriched": { "function": "Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration o", "gene_name": "KCNJ9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92806" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Neurodegenerative Disorders (general)", "glycan_involvement": "N-glycosylation is essential for SYP trafficking to synaptic vesicles.", "mechanism": "SYP upregulation indicates synaptic maturation in reprogrammed neurons; synaptic loss is a feature of neurodegeneration.", "protein": "SYP", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Neurodegenerative Disorders (general)", "glycan_involvement": "Glycosylation modulates MAP2 stability and microtubule binding.", "mechanism": "MAP2 marks mature neurons; loss of MAP2 is associated with neurodegeneration.", "protein": "MAP2", "protein_enriched": { "function": "The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules", "gene_name": "MAP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11137" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "medium", "disease": "Aging-related neuronal dysfunction", "glycan_involvement": "O-glycosylation affects Tau aggregation propensity.", "mechanism": "Tau expression is used to confirm neuronal identity; abnormal Tau is linked to aging and neurodegeneration.", "protein": "Tau (MAPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "low", "disease": "Neurodegenerative Disorders (general)", "glycan_involvement": "Glycosylation may regulate NeuN nuclear localization.", "mechanism": "NeuN is a marker for mature neurons; loss of NeuN is seen in neuronal loss.", "protein": "NeuN (RBFOX3)", "relationship_type": "biomarker", "source_pmcid": "PMC12143395" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates ICAM-1 stability and leukocyte adhesion.", "mechanism": "PM10 exposure increases ICAM-1 expression via DNA hypomethylation, promoting inflammation and vascular complications.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation required for VCAM-1 function in leukocyte recruitment.", "mechanism": "PM10 exposure upregulates VCAM-1, contributing to endothelial dysfunction and inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "CRP glycosylation affects its clearance and function.", "mechanism": "PM10 exposure increases CRP, indicating systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Alcohol use disorder", "glycan_involvement": "N-glycosylation essential for TLR4 trafficking and signaling.", "mechanism": "Alcohol activates TLR4, leading to neuroinflammation via chromatin remodeling.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation required for CD14 function.", "mechanism": "PM10 exposure reduces DNA methylation of CD14, increasing its expression and inflammatory response.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation may affect NOS2 stability.", "mechanism": "PM2.5/PM10 exposure causes hypomethylation and overexpression of NOS2, increasing nitric oxide and cancer risk.", "protein": "NOS2 (iNOS)", "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "BDNF is glycosylated, which affects secretion and function.", "mechanism": "Mercury exposure increases H3K27me3 and decreases acetylation at BDNF promoter, repressing expression and impairing cognition.", "protein": "BDNF", "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "MT-1 is a glycoprotein; glycosylation may affect its stability.", "mechanism": "Arsenic exposure silences MT-1 via DNA hypermethylation, reducing detoxification and promoting carcinogenesis.", "protein": "Metallothionein-1 (MT-1)", "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Congenital heart disease", "glycan_involvement": "Potential O-glycosylation may regulate GATA4 activity.", "mechanism": "PM2.5 and arsenic exposure increase histone acetylation at GATA4 promoter, upregulating expression and causing cardiac malformations.", "protein": "GATA4", "protein_enriched": { "function": "Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development and function (PubMed:24000169, PubMed:27984724, PubMed:35182466). In cooperation", "gene_name": "GATA4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43694" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "O-GlcNAc modification regulates NF-\u03baB transcriptional activity.", "mechanism": "Cadmium and PM exposure increase NF-\u03baB acetylation, enhancing pro-inflammatory gene expression.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12143666" }, { "confidence": "high", "disease": "Varicella (chickenpox)", "glycan_involvement": "gE is glycosylated; glycosylation is essential for antigenicity and immune recognition.", "mechanism": "VZV gE is the immunodominant antigen; IgG antibodies against gE indicate exposure or immunity.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "high", "disease": "Varicella (chickenpox)", "glycan_involvement": "Glycosylation of gE affects vaccine efficacy and antibody binding.", "mechanism": "gE is the main target of neutralizing antibodies induced by VarV vaccination.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143688" }, { "confidence": "medium", "disease": "Breakthrough varicella", "glycan_involvement": "Glycosylation status may influence immune escape and antibody recognition.", "mechanism": "Low or waning IgG against gE correlates with increased risk of breakthrough infection.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "medium", "disease": "Varicella (chickenpox)", "glycan_involvement": "gB glycosylation modulates antigenicity.", "mechanism": "gB is a secondary antigen; IgG against gB supports diagnosis and immune status.", "protein": "Varicella-zoster virus glycoprotein B (gB)", "protein_enriched": { "function": "The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane f", "gene_name": "gH", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P09260" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "medium", "disease": "Varicella (chickenpox)", "glycan_involvement": "gH glycosylation is important for function and immune recognition.", "mechanism": "gH is involved in viral entry; antibodies against gH contribute to immunity.", "protein": "Varicella-zoster virus glycoprotein H (gH)", "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "high", "disease": "Varicella (chickenpox)", "glycan_involvement": "Glycosylation of gE is required for proper immune response.", "mechanism": "High levels of anti-gE IgG (above 100 mIU/mL) are protective against varicella.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "protective", "source_pmcid": "PMC12143688" }, { "confidence": "medium", "disease": "Breakthrough varicella", "glycan_involvement": "Altered glycosylation may reduce immunogenicity.", "mechanism": "Insufficient anti-gE IgG due to waning immunity or suboptimal glycosylation increases breakthrough risk.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12143688" }, { "confidence": "low", "disease": "Varicella (chickenpox)", "glycan_involvement": "gI glycosylation affects antigenicity.", "mechanism": "gI is a minor antigen; IgG against gI may indicate exposure.", "protein": "Varicella-zoster virus glycoprotein I (gI)", "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "low", "disease": "Varicella (chickenpox)", "glycan_involvement": "gL glycosylation is important for complex formation.", "mechanism": "gL forms a complex with gH; antibodies against gL may contribute to immunity.", "protein": "Varicella-zoster virus glycoprotein L (gL)", "protein_enriched": { "function": "Abundant tegument protein. Trans-activates the immediate early genes (By similarity)", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09264" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "high", "disease": "Varicella (chickenpox)", "glycan_involvement": "Glycosylation of gE is critical for ELISA antigenicity.", "mechanism": "ELISA assays using gE detect VZV IgG for seroepidemiological surveillance.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "biomarker", "source_pmcid": "PMC12143688" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "EGFR is a heavily N-glycosylated receptor; glycosylation affects ligand binding and signaling.", "mechanism": "EGFR siRNA silencing inhibits tumor cell survival, proliferation, invasion, and metastasis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Angiogenesis-related tumor progression", "glycan_involvement": "VEGF is glycosylated; glycosylation modulates its secretion and activity.", "mechanism": "Downregulation of VEGF by GM and siEGFR inhibits angiogenesis and tumor growth.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "CXCL12 is glycosylated; glycosylation affects chemokine-receptor interactions.", "mechanism": "Downregulation of CXCL12 by GM and siEGFR reduces tumor cell migration and metastasis.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans exposed upon endosomal rupture.", "mechanism": "Galectin-3 recruitment indicates endosomal membrane disruption, facilitating siRNA release.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Angiogenesis-related tumor progression", "glycan_involvement": "EGFR glycosylation modulates receptor function and downstream signaling.", "mechanism": "EGFR silencing reduces VEGF expression, inhibiting angiogenesis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Tumor metastasis", "glycan_involvement": "VEGF glycosylation is required for proper folding and secretion.", "mechanism": "VEGF promotes angiogenesis and metastatic spread of tumor cells.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12143824" }, { "confidence": "medium", "disease": "Angiogenesis-related tumor progression", "glycan_involvement": "CXCL12 glycosylation affects its stability and receptor binding.", "mechanism": "CXCL12 promotes endothelial tube formation and angiogenesis.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "causal", "source_pmcid": "PMC12143824" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Galectin-3 recognizes glycan motifs exposed during membrane damage.", "mechanism": "Galectin-3 puncta formation marks endosomal disruption, a process relevant to drug delivery in cancer cells.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Tumor metastasis", "glycan_involvement": "EGFR glycosylation influences receptor dimerization and signaling.", "mechanism": "EGFR silencing reduces tumor cell migration and metastatic potential.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Liver cancer (Hepatocellular carcinoma)", "glycan_involvement": "VEGF glycosylation is essential for its angiogenic activity.", "mechanism": "VEGF downregulation by GM and siEGFR inhibits tumor vascularization and growth.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143824" }, { "confidence": "high", "disease": "Advanced urothelial carcinoma", "glycan_involvement": "Nectin-4 is a glycoprotein; glycosylation may affect antibody binding and cell surface expression.", "mechanism": "Nectin-4 is targeted by enfortumab vedotin for selective delivery of cytotoxic MMAE to tumor cells.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12143863" }, { "confidence": "medium", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Glycosylation may modulate Nectin-4 function and antibody interaction.", "mechanism": "EV targeting Nectin-4 may inhibit PI3K/AKT insulin signaling, leading to insulin resistance and DKA.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "high", "disease": "Skin disorders", "glycan_involvement": "Glycosylation may affect Nectin-4 localization and immune recognition.", "mechanism": "Nectin-4 expression in skin mediates EV-induced skin toxicity.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Possible modulation of neural cell adhesion via glycosylation.", "mechanism": "Nectin-4 targeting by EV associated with peripheral neuropathy as an adverse event.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "high", "disease": "Acute tubulointerstitial nephritis", "glycan_involvement": "Glycosylation affects stability and renal filtration.", "mechanism": "Elevated urinary \u03b22-microglobulin indicates renal tubular injury during DKA/EV therapy.", "protein": "\u03b22-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12143863" }, { "confidence": "high", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Insulin glycosylation affects receptor binding and clearance.", "mechanism": "High insulin levels with DKA indicate severe insulin resistance during EV therapy.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12143863" }, { "confidence": "high", "disease": "Diabetic ketoacidosis (DKA)", "glycan_involvement": "Glycosylation may affect peptide stability.", "mechanism": "Elevated C-peptide distinguishes EV-induced DKA from ICI-induced type 1 diabetes.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12143863" }, { "confidence": "medium", "disease": "Drug-induced hyperglycemia", "glycan_involvement": "Glycosylation may influence Nectin-4-mediated signaling.", "mechanism": "EV targeting Nectin-4 impairs insulin signaling, causing hyperglycemia.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "low", "disease": "Acute tubulointerstitial nephritis", "glycan_involvement": "Glycosylation may affect tissue-specific expression.", "mechanism": "EV-induced renal injury may be mediated by Nectin-4 expression in renal tissue.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "low", "disease": "Respiratory failure", "glycan_involvement": "Glycosylation may modulate tissue targeting.", "mechanism": "EV-induced multi-organ toxicity may involve Nectin-4-expressing tissues.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12143863" }, { "confidence": "high", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "N-glycosylation and O-fucosylation required for secretion; impaired glycosylation reduces ECM deposition.", "mechanism": "Pathogenic variants impair secretion and ECM incorporation, leading to disorganized ECM and disease phenotype.", "protein": "ADAMTSL2", "relationship_type": "causal", "source_pmcid": "PMC12144124" }, { "confidence": "high", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "Glycosylation required for proper folding and secretion; defects reduce ECM accumulation.", "mechanism": "Mutations in exons 41/42 impair secretion and ECM incorporation, disrupting microfibril organization.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "causal", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "Glycosylation affects ECM deposition; reduced in patient cells.", "mechanism": "Reduced ECM accumulation in GD fibroblasts reflects impaired matrix organization.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144124" }, { "confidence": "high", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "Glycosylation may affect secretion/activity; not directly addressed.", "mechanism": "Upregulated in GD fibroblasts, drives enhanced cell migration and ECM degradation.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144124" }, { "confidence": "high", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "Glycosylation may affect membrane localization/activity; not directly addressed.", "mechanism": "Upregulated in GD fibroblasts and tissues, promotes cell migration and ECM remodeling.", "protein": "MMP-14", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Not specified.", "mechanism": "Elevated in heart failure, associated with arterial hypertension and tissue remodeling.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "Increased in atherosclerosis, involved in altered cell migration and vascular remodeling.", "protein": "MMP-14", "relationship_type": "biomarker", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Idiopathic pulmonary fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Increased in disease, contributes to ECM degradation and fibrosis.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Not specified.", "mechanism": "Upregulated by smoking, associated with early-onset lung cancer and tissue invasion.", "protein": "MMP-14", "relationship_type": "biomarker", "source_pmcid": "PMC12144124" }, { "confidence": "medium", "disease": "Geleophysic dysplasia (GD)", "glycan_involvement": "Not specified.", "mechanism": "Pathogenic variants cause GD3, affecting TGF-beta regulation and ECM organization.", "protein": "LTBP3", "relationship_type": "causal", "source_pmcid": "PMC12144124" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP elevation reflects systemic inflammation and predicts vascular events.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12144132" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "IL-6 is glycosylated, which modulates receptor binding and signaling.", "mechanism": "IL-6 promotes glomerular and interstitial inflammation, leading to fibrosis.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "TNF-\u03b1 glycosylation influences secretion and receptor interaction.", "mechanism": "TNF-\u03b1 induces insulin resistance and adipose inflammation.", "protein": "Tumor necrosis factor alpha", "relationship_type": "causal", "source_pmcid": "PMC12144132" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "Ferritin is glycosylated; glycan changes reflect inflammatory state.", "mechanism": "Elevated ferritin indicates macrophage activation and hyperinflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "D-dimer is a glycopeptide; glycosylation affects clearance.", "mechanism": "D-dimer elevation signals hypercoagulability and thrombotic risk.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "LDH is glycosylated, which may affect serum half-life.", "mechanism": "LDH elevation reflects tissue injury, including renal damage.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12144132" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates IL-6 receptor binding.", "mechanism": "IL-6 drives vascular inflammation and atherogenesis.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation affects CRP's inflammatory activity.", "mechanism": "CRP elevation is associated with CKD progression.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 bioactivity.", "mechanism": "TNF-\u03b1 impairs insulin signaling, promoting diabetes.", "protein": "Tumor necrosis factor alpha", "relationship_type": "causal", "source_pmcid": "PMC12144132" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Cell surface glycosylation regulates adhesion and migration.", "mechanism": "Altered immune cell glycoproteins mediate vascular inflammation.", "protein": "Neutrophil/lymphocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12144132" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "KIM-1 is heavily N-glycosylated, which is essential for its cell surface expression and function as a biomarker.", "mechanism": "Upregulated in proximal tubular cells after nephrotoxic or ischemic injury; indicates kidney damage.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Cellular oxidative stress", "glycan_involvement": "Extracellular SOD is glycosylated, affecting stability and secretion.", "mechanism": "Altered SOD expression reflects oxidative stress in kidney tissue after nanoparticle exposure.", "protein": "SOD", "relationship_type": "biomarker", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Kidney inflammation", "glycan_involvement": "Potential N-glycosylation may regulate enzyme activity and localization.", "mechanism": "Upregulation correlates with acute and chronic inflammation in response to nanoparticle dose.", "protein": "NOS2/iNOS", "relationship_type": "biomarker", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Apoptosis-related kidney injury", "glycan_involvement": "Possible glycosylation may affect apoptotic signaling.", "mechanism": "Elevated BAX promotes apoptosis in kidney cells exposed to nanoparticles.", "protein": "BAX", "relationship_type": "causal", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Apoptosis-related kidney injury", "glycan_involvement": "Potential glycosylation may modulate apoptotic activity.", "mechanism": "Increased BID expression triggers intrinsic apoptosis in kidney tissue.", "protein": "BID", "relationship_type": "causal", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "IGF-2 is glycosylated, which is critical for secretion and receptor binding.", "mechanism": "Elevated IGF-2 linked to cell survival/apoptosis and CKD progression.", "protein": "IGF-2", "relationship_type": "causal", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Kidney inflammation", "glycan_involvement": "Glycosylation modulates ligand-receptor interactions and immune signaling.", "mechanism": "Upregulation sustains chronic inflammation in low-dose nanoparticle exposure.", "protein": "CD40L", "relationship_type": "causal", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Kidney inflammation", "glycan_involvement": "N-glycosylation affects receptor function and immune activation.", "mechanism": "Elevated CD40 expression promotes inflammatory signaling in kidney tissue.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "causal", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Not glycosylated.", "mechanism": "Transient upregulation acts as an adaptive response limiting inflammation and damage.", "protein": "FOS (Apo-1)", "protein_enriched": { "function": "Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symm", "gene_name": "FOS", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P01100" }, "relationship_type": "protective", "source_pmcid": "PMC12144138" }, { "confidence": "medium", "disease": "Nephrotoxicity", "glycan_involvement": "Potential O-glycosylation may regulate chaperone activity.", "mechanism": "Upregulation protects against cellular stress and apoptosis in kidney tissue.", "protein": "HSP27", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12144138" }, { "confidence": "high", "disease": "Ovarian serous cystadenocarcinoma", "glycan_involvement": "CA-125 is a heavily O-glycosylated mucin; glycosylation is essential for its secretion and immunoreactivity.", "mechanism": "CA-125 is overexpressed by malignant ovarian epithelial cells and released into circulation.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "high", "disease": "Peritoneal tuberculosis", "glycan_involvement": "Glycosylation enables CA-125 release from inflamed peritoneal cells.", "mechanism": "CA-125 is expressed by mesothelial cells lining the peritoneum; inflammation in PTB increases serum levels.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Mucin-type glycosylation is required for CA-125 function and detection.", "mechanism": "CA-125 is expressed by endometrial cells; levels rise in endometriosis due to ectopic endometrial tissue.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "medium", "disease": "Pelvic inflammatory disease", "glycan_involvement": "Glycosylation facilitates CA-125 release during inflammation.", "mechanism": "Inflammation of pelvic organs increases CA-125 secretion from epithelial and mesothelial cells.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "high", "disease": "Peritoneal carcinomatosis", "glycan_involvement": "O-glycosylation is critical for CA-125 structure and immunodetection.", "mechanism": "Disseminated malignancy in the peritoneum stimulates CA-125 production by mesothelial cells.", "protein": "CA-125", "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "medium", "disease": "Ovarian serous cystadenocarcinoma", "glycan_involvement": "CA 19-9 is a sialylated Lewis antigen; glycosylation determines antigenicity.", "mechanism": "CA 19-9 may be elevated in ovarian cancer due to aberrant glycosylation in tumor cells.", "protein": "CA 19-9", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:17502375, PubMed:22932902). Mediates transport of beta-alanine (PubMed:17502375). Can also mediate transport", "gene_name": "SLC6A13", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NSD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "medium", "disease": "Peritoneal tuberculosis", "glycan_involvement": "Glycosylation of cell surface proteins leads to CA 19-9 epitope expression.", "mechanism": "CA 19-9 can be elevated in PTB due to inflammation and reactive changes in peritoneal cells.", "protein": "CA 19-9", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:17502375, PubMed:22932902). Mediates transport of beta-alanine (PubMed:17502375). Can also mediate transport", "gene_name": "SLC6A13", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NSD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144375" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "P-gp is a glycoprotein; glycosylation affects its membrane localization and function.", "mechanism": "P-gp mediates efflux of curcumin, limiting its bioavailability and potential anticancer effects.", "protein": "P-glycoprotein (P-gp, ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144411" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation modulates P-gp stability and trafficking.", "mechanism": "Efflux of curcumin by P-gp reduces its anti-inflammatory potential.", "protein": "P-glycoprotein (P-gp, ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144411" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "\u03b2-glucuronidase is a glycoprotein; glycosylation is required for its lysosomal targeting and activity.", "mechanism": "Local \u03b2-glucuronidase expression may deconjugate curcumin-glucuronide, increasing local unconjugated curcumin and potential anticancer activity.", "protein": "\u03b2-glucuronidase", "protein_enriched": { "function": "Plays an important role in the degradation of dermatan and keratan sulfates", "gene_name": "GUSB", "glycan_count": 42, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G06231AO", "G08290VR", "G15664MX", "G20212GT", "G25079LO", "G31852PQ", "G39619TI", "G40702WU", "G41247ZX", "G45504EY", "G46503DX", "G46524LG", "G47448YK", "G48584BU", "G60834IK", "G62765YT", "G64020XR", "G64527OM", "G65000LJ", "G70101JE", "G72747WU", "G80920RR", "G83161QT", "G83460ZZ", "G83633GK", "G84862VB", "G89864BN", "G92062TF", "G96430BV", "G02815KT", "G28681TP", "G50282JC", "G51653BI", "G70441OD", "G74724QE", "G84349RE", "G90575OW", "G92050GC", "G92275SC", "G49108TO", "G06110VR", "G39188ZX" ], "uniprot_id": "P08236" }, "relationship_type": "protective", "source_pmcid": "PMC12144411" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation affects enzyme stability and secretion.", "mechanism": "Bacterial \u03b2-glucuronidase in the gut may deconjugate curcumin-glucuronide, increasing local curcumin concentrations and anti-inflammatory effects.", "protein": "\u03b2-glucuronidase", "protein_enriched": { "function": "Plays an important role in the degradation of dermatan and keratan sulfates", "gene_name": "GUSB", "glycan_count": 42, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G06231AO", "G08290VR", "G15664MX", "G20212GT", "G25079LO", "G31852PQ", "G39619TI", "G40702WU", "G41247ZX", "G45504EY", "G46503DX", "G46524LG", "G47448YK", "G48584BU", "G60834IK", "G62765YT", "G64020XR", "G64527OM", "G65000LJ", "G70101JE", "G72747WU", "G80920RR", "G83161QT", "G83460ZZ", "G83633GK", "G84862VB", "G89864BN", "G92062TF", "G96430BV", "G02815KT", "G28681TP", "G50282JC", "G51653BI", "G70441OD", "G74724QE", "G84349RE", "G90575OW", "G92050GC", "G92275SC", "G49108TO", "G06110VR", "G39188ZX" ], "uniprot_id": "P08236" }, "relationship_type": "protective", "source_pmcid": "PMC12144411" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates P-gp function.", "mechanism": "Efflux of curcumin by P-gp may limit its systemic antidiabetic effects.", "protein": "P-glycoprotein (P-gp, ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144411" }, { "confidence": "low", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "Glycosylation affects P-gp function at the blood-brain barrier.", "mechanism": "P-gp efflux limits curcumin brain penetration, reducing its neuroprotective potential.", "protein": "P-glycoprotein (P-gp, ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144411" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation required for enzyme activity.", "mechanism": "High \u03b2-glucuronidase activity in tumors may indicate potential for local curcumin activation.", "protein": "\u03b2-glucuronidase", "protein_enriched": { "function": "Plays an important role in the degradation of dermatan and keratan sulfates", "gene_name": "GUSB", "glycan_count": 42, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G06231AO", "G08290VR", "G15664MX", "G20212GT", "G25079LO", "G31852PQ", "G39619TI", "G40702WU", "G41247ZX", "G45504EY", "G46503DX", "G46524LG", "G47448YK", "G48584BU", "G60834IK", "G62765YT", "G64020XR", "G64527OM", "G65000LJ", "G70101JE", "G72747WU", "G80920RR", "G83161QT", "G83460ZZ", "G83633GK", "G84862VB", "G89864BN", "G92062TF", "G96430BV", "G02815KT", "G28681TP", "G50282JC", "G51653BI", "G70441OD", "G74724QE", "G84349RE", "G90575OW", "G92050GC", "G92275SC", "G49108TO", "G06110VR", "G39188ZX" ], "uniprot_id": "P08236" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144411" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CD47 is a heavily glycosylated transmembrane protein; glycosylation is essential for its cell-surface localization and function.", "mechanism": "CD47 is highly expressed on tumor cells, delivering a 'don't eat me' signal via Sirp\u03b1 to inhibit macrophage phagocytosis.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144523" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation maintains CD47 stability and interaction with Sirp\u03b1.", "mechanism": "Overexpression of CD47 enables immune evasion by blocking macrophage-mediated clearance.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Immunotherapy resistance", "glycan_involvement": "Glycosylation status may affect antibody recognition and therapeutic efficacy.", "mechanism": "High CD47 expression correlates with poor prognosis and resistance to immunotherapy.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144523" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "Sirp\u03b1 is a glycoprotein; glycosylation may modulate ligand binding.", "mechanism": "Sirp\u03b1 on macrophages binds CD47 on tumor cells, inhibiting phagocytosis and promoting immune escape.", "protein": "Sirp\u03b1 (SIRPA)", "relationship_type": "causal", "source_pmcid": "PMC12144523" }, { "confidence": "high", "disease": "Tumor metastasis", "glycan_involvement": "CD206 is a C-type lectin recognizing glycan structures; its own glycosylation is required for function.", "mechanism": "CD206 is highly expressed on M2-like macrophages, which promote tumor progression and metastasis.", "protein": "CD206 (Mannose receptor, MRC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Solid tumors (general)", "glycan_involvement": "CD86 is glycosylated, which is important for its costimulatory function.", "mechanism": "Upregulation of CD86 marks M1-like macrophages, associated with antitumor immunity.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "protective", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Solid tumors (general)", "glycan_involvement": "Glycosylation is required for CD80 surface expression and function.", "mechanism": "CD80 upregulation on dendritic cells indicates maturation and enhanced T cell activation.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "protective", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "CD68 is a lysosomal glycoprotein; glycosylation affects stability.", "mechanism": "CD68 marks macrophages; high CD68+ M2 macrophage infiltration correlates with immunosuppression.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "ARG1 is glycosylated, which may affect secretion and activity.", "mechanism": "ARG1 is expressed by M2-like macrophages, suppressing T cell responses and promoting tumor growth.", "protein": "Arginase-1 (ARG1)", "relationship_type": "causal", "source_pmcid": "PMC12144523" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "IL-10 is glycosylated, which is important for stability and secretion.", "mechanism": "IL-10 secretion by M2-like macrophages suppresses antitumor immunity.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC12144523" }, { "confidence": "high", "disease": "Diabetic Encephalopathy", "glycan_involvement": "N-glycosylation modulates AKT1 stability and localization.", "mechanism": "Regulates PI3K/Akt signaling, promoting neuronal survival and synaptic plasticity; KWG metabolites (N8) bind and activate AKT1.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "high", "disease": "Diabetic Encephalopathy", "glycan_involvement": "Glycosylation affects TNF secretion and receptor binding.", "mechanism": "Drives neuroinflammation and oxidative stress, exacerbating BBB disruption; KWG metabolites (N4) inhibit TNF activity.", "protein": "TNF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "medium", "disease": "Diabetic Encephalopathy", "glycan_involvement": "N-glycosylation regulates SRC kinase activity and signaling.", "mechanism": "Promotes microglial cytokine release and neurodegeneration; 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KWG metabolites (N1) activate ESR1.", "protein": "ESR1", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12144589" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation influences AKT1 function in neurons.", "mechanism": "AKT1 dysfunction linked to neurodegeneration; KWG metabolites may restore AKT1 signaling.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation regulates TNF bioactivity.", "mechanism": "TNF is a key mediator of neuroinflammatory processes; KWG metabolites suppress TNF signaling.", "protein": "TNF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "medium", "disease": "Blood-Brain Barrier Dysfunction", "glycan_involvement": "N-glycosylation required for EGFR surface expression.", "mechanism": "EGFR activation disrupts BBB integrity; KWG metabolites inhibit EGFR to protect BBB.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "medium", "disease": "Cognitive Decline", "glycan_involvement": "N-glycosylation affects SRC localization in neurons.", "mechanism": "SRC kinase activation contributes to synaptic dysfunction; KWG metabolites inhibit SRC.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "O-glycosylation modulates ESR1-mediated neuroprotection.", "mechanism": "ESR1 activation reduces neurodegeneration and inflammation; KWG metabolites enhance ESR1 activity.", "protein": "ESR1", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12144589" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Extensive N- and O-glycosylation modulates ligand binding and cell surface expression.", "mechanism": "CD24 overexpression correlates with poor prognosis and chemoresistance via p38MAPK pathway activation.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Sialylation enables Siglec-10 binding; glycosylation affects cell adhesion and immune escape.", "mechanism": "CD24 marks cancer stem cells, mediates chemoresistance to cisplatin/doxorubicin, and immune evasion via Siglec-10 interaction.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation regulates ligand interactions and stemness.", "mechanism": "CD24+ cancer stem cells drive chemoresistance to gemcitabine and radiotherapy via Wnt/TGF-\u03b2 and STAT3/EMT pathways.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation influences cell adhesion and metastatic potential.", "mechanism": "CD24 overexpression is associated with shortened metastasis-free survival and poor prognosis.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma", "glycan_involvement": "Glycosylation affects lipid raft localization and signaling.", "mechanism": "CD24+ cells exhibit cisplatin and radiotherapy resistance via DNA repair gene modulation and stemness.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Leukemia", "glycan_involvement": "Glycosylation modulates immune checkpoint function.", "mechanism": "CD24 is highly expressed in leukemia stem cells, mediates chemoresistance via Wnt-\u03b2-catenin and PI3K-Akt pathways.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12144611" }, { "confidence": "medium", "disease": "Retinoblastoma", "glycan_involvement": "Glycosylation required for lipid raft recruitment and signaling.", "mechanism": "CD24 activates PTEN/AKT/mTORC1 pathway, induces autophagy, and reduces vincristine sensitivity.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation modulates cell surface expression and signaling.", "mechanism": "SOX2-driven CD24 upregulation promotes resistance to BRAF inhibitors; knockdown restores drug sensitivity.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects cell signaling and drug response.", "mechanism": "CD24 overexpression induces autophagy via PP2A/AKT/mTOR pathway, leading to sorafenib resistance.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "medium", "disease": "Malignant mesothelioma", "glycan_involvement": "Glycosylation impacts antibody binding and cell invasiveness.", "mechanism": "CD24 antibody inhibits growth and stemness; CD24-deficient cells are more drug-sensitive.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144611" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "VEGF-A is a homodimeric glycoprotein; glycosylation is essential for stability and receptor binding.", "mechanism": "Promotes angiogenesis via VEGFR2 signaling, supporting tumor growth and metastasis.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "VEGFR2 is a glycoprotein; glycosylation affects ligand binding and receptor activation.", "mechanism": "VEGFR2 mediates VEGF-induced angiogenesis; targeted by drugs (e.g., bevacizumab, sunitinib) to inhibit tumor vascularization.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144631" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "DLL4 is a glycoprotein ligand; glycosylation may affect Notch receptor interaction.", "mechanism": "Regulates vascular sprouting and branching; inhibition leads to non-functional neovessels and reduced tumor blood supply.", "protein": "DLL4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144631" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "JAG1 is a glycoprotein ligand; glycosylation modulates Notch pathway activation.", "mechanism": "Promotes angiogenesis via Notch signaling; associated with increased vessel numbers in TNBC.", "protein": "JAG1", "protein_enriched": { "function": "Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). S", "gene_name": "JAG1", "glycan_count": 5, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G27058EU", "G41071NU", "G42124LM", "G57321FI" ], "uniprot_id": "P78504" }, "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "EPHA2 is a glycoprotein; glycosylation may influence receptor function and exosomal packaging.", "mechanism": "Exosomal EPHA2 promotes angiogenesis in endothelial cells via AMPK signaling.", "protein": "EPHA2", "protein_enriched": { "function": "Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The s", "gene_name": "EPHA2", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G41071NU", "G02815KT", "G05724UK", "G10256JP", "G14669DU", "G28681TP", "G49108TO" ], "uniprot_id": "P29317" }, "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycan epitope; aberrant glycosylation is a hallmark of cancer.", "mechanism": "Exosomal TF-Ag-\u03b1 (Gal\u03b21-3GalNAc-\u03b1) serves as a carbohydrate marker for breast cancer detection with >95% accuracy.", "protein": "TF-Ag-\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12144631" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "VEGF-C is a glycoprotein; glycosylation required for secretion and receptor interaction.", "mechanism": "Promotes lymphangiogenesis and metastasis via VEGFR2/VEGFR3 signaling.", "protein": "VEGF-C", "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "VEGF-D is a glycoprotein; glycosylation affects bioactivity.", "mechanism": "Facilitates angiogenesis and lymphangiogenesis, contributing to tumor spread.", "protein": "VEGF-D", "protein_enriched": { "function": "Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May functi", "gene_name": "VEGFD", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43915" }, "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "PLGF is a glycoprotein; glycosylation influences receptor binding.", "mechanism": "Binds VEGFR1, promoting angiogenesis and tumor progression.", "protein": "PLGF", "relationship_type": "causal", "source_pmcid": "PMC12144631" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation critical for VEGF-A function.", "mechanism": "Targeted by bevacizumab to inhibit angiogenesis and tumor growth.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144631" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation modulates cell-cell adhesion and EMT.", "mechanism": "Downregulation promotes EMT and invasiveness in HCC cells after uptake of hypoxia-induced exosomes.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation affects cell motility and EMT.", "mechanism": "Upregulation promotes EMT and migration in HCC cells after exosome uptake.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "O-glycosylation may regulate filament assembly and EMT.", "mechanism": "Upregulation is a marker of EMT and increased invasiveness in HCC cells.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Potential glycosylation may affect stability and transcriptional activity.", "mechanism": "Upregulated by exosomal lncRNA-PVT1 via miR-345-5p ceRNA mechanism, promoting EMT and tumor progression.", "protein": "FoxM1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12144658" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation may influence nuclear localization and function.", "mechanism": "Upregulated in tumors with increased invasiveness post-exosome uptake; marker of proliferation.", "protein": "Ki67", "protein_enriched": { "function": "Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:3287", "gene_name": "MKI67", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P46013" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity.", "mechanism": "Upregulated in highly invasive tumors; promotes ECM degradation and metastasis.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not a glycoprotein; acts via exosomal transport.", "mechanism": "Exosomal lncRNA-PVT1 upregulated post-hypoxia/TACE, promotes EMT via miR-345-5p/FoxM1 axis.", "protein": "lncRNA-PVT1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Cancer recurrence post-TACE", "glycan_involvement": "Not a glycoprotein.", "mechanism": "High plasma exosomal lncRNA-PVT1 predicts early recurrence and poor prognosis after TACE.", "protein": "lncRNA-PVT1", "relationship_type": "biomarker", "source_pmcid": "PMC12144658" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated in carcinoma tissues; associated with hypoxia and EMT.", "protein": "GAPLINC", "relationship_type": "biomarker", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "EMT-associated metastasis", "glycan_involvement": "N-glycosylation essential for activity.", "mechanism": "Promotes extracellular matrix breakdown, facilitating metastasis during EMT.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12144658" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation is essential for fetuin-A secretion and function.", "mechanism": "Fetuin-A inhibits insulin receptor tyrosine kinase, promoting insulin resistance and increasing T2DM risk.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects fetuin-A stability and serum levels.", "mechanism": "Elevated fetuin-A is associated with increased risk of CVD, myocardial infarction, and ischemic stroke.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12144694" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for fetuin-A's endocrine activity.", "mechanism": "High fetuin-A levels are linked to obesity and metabolic syndrome.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "CRP is glycosylated; glycosylation affects its stability and immune function.", "mechanism": "Elevated hs-CRP predicts cardiovascular complications in T2DM.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "High hs-CRP levels are linked to increased risk of cardiovascular events.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for receptor interaction.", "mechanism": "Fetuin-A inhibits insulin signaling, promoting insulin resistance.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Upregulation of SIRT1 improves metabolic regulation and insulin sensitivity.", "protein": "Sirtuin 1 (SIRT1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "SIRT1 preserves cardiovascular homeostasis and protects against myocardial infarction and endothelial dysfunction.", "protein": "Sirtuin 1 (SIRT1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects fetuin-A's diagnostic utility.", "mechanism": "High fetuin-A is a marker for metabolic syndrome-related disorders.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation impacts fetuin-A's serum levels and diagnostic accuracy.", "mechanism": "Fetuin-A may be used as a diagnostic marker for liver dysfunction.", "protein": "Fetuin-A (alpha-2-Heremans-Schmid glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12144694" }, { "confidence": "high", "disease": "STEMI", "glycan_involvement": "Troponin is a glycoprotein; glycosylation may affect clearance and detection.", "mechanism": "Elevated circulating troponin indicates myocardial injury; higher in T2D STEMI patients.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12144705" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "CRP glycosylation modulates its function and clearance.", "mechanism": "CRP is elevated in T2D STEMI patients, reflecting systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144705" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation regulates leukocyte adhesion and migration.", "mechanism": "Increased leukocyte count and activation contribute to myocardial injury and poor prognosis.", "protein": "Leukocyte cell surface glycoproteins (CD antigens)", "relationship_type": "causal", "source_pmcid": "PMC12144705" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and receptor interaction.", "mechanism": "Insulin resistance and hyperinsulinemia are central to T2D pathogenesis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144705" }, { "confidence": "medium", "disease": "HFpEF", "glycan_involvement": "Glycosylation affects peptide stability and detection.", "mechanism": "Elevated in HFpEF; reflects cardiac stress and dysfunction.", "protein": "Natriuretic peptides (BNP/NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12144705" }, { "confidence": "medium", "disease": "Cardio-hepatic syndrome", "glycan_involvement": "N-glycosylation changes in transferrin are markers of hepatic injury.", "mechanism": "Altered glycosylation patterns in transferrin may reflect liver dysfunction in T2D STEMI.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144705" }, { "confidence": "high", "disease": "Skeletal muscle dysfunction", "glycan_involvement": "Glycogen is a glucose polymer; its synthesis and degradation are regulated by glycosylation enzymes.", "mechanism": "Altered glycogen metabolism in T2D leads to muscle energy deficit.", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC12144705" }, { "confidence": "medium", "disease": "Cardio-hepatic syndrome", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated ALT indicates liver injury secondary to cardiac dysfunction in T2D STEMI.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144705" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "SGLT2 is a glycoprotein; glycosylation affects membrane localization.", "mechanism": "SGLT2 inhibitors used for glycemic control in T2D; may impact cardiovascular outcomes.", "protein": "SGLT2", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate ", "gene_name": "DYRK1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144705" }, { "confidence": "low", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation may affect transporter function.", "mechanism": "Low magnesium in T2D STEMI patients increases arrhythmia risk.", "protein": "Magnesium transporter (TRPM6/7)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12144705" }, { "confidence": "high", "disease": "HBV-ACLF", "glycan_involvement": "RC is carried by glycosylated lipoproteins (VLDL, IDL, chylomicron remnants).", "mechanism": "Elevated RC predicts poor 28- and 90-day prognosis; associated with worse liver function and coagulation.", "protein": "Remnant cholesterol (RC)", "relationship_type": "biomarker", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "RC is transported by glycosylated lipoproteins.", "mechanism": "High RC associated with increased NAFLD risk and complications.", "protein": "Remnant cholesterol (RC)", "relationship_type": "biomarker", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation of lipoproteins affects RC metabolism.", "mechanism": "RC levels positively correlated with insulin resistance in MAFLD.", "protein": "Remnant cholesterol (RC)", "relationship_type": "causal", "source_pmcid": "PMC12144760" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylated lipoproteins facilitate RC transport and vascular interaction.", "mechanism": "RC promotes atherogenesis via endothelial penetration and foam cell formation.", "protein": "Remnant cholesterol (RC)", "relationship_type": "causal", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "HBV-ACLF", "glycan_involvement": "LDL particles are glycosylated, affecting clearance and function.", "mechanism": "Decreased LDL-c is an independent risk factor for poor survival in HBV-ACLF.", "protein": "LDL-c", "relationship_type": "biomarker", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "HBV-ACLF", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties.", "mechanism": "HDL-c reduces inflammation and neutralizes endotoxins, potentially improving prognosis.", "protein": "HDL-c", "relationship_type": "protective", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "ApoC-III is glycosylated, affecting its function in lipoprotein metabolism.", "mechanism": "Inhibition of ApoC-III lowers RC and reduces cardiovascular risk.", "protein": "Apolipoprotein C-III", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Inhibition reduces RC and atherogenic lipoproteins.", "protein": "Angiopoietin-like 3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144760" }, { "confidence": "low", "disease": "HBV-ACLF", "glycan_involvement": "LCAT is glycosylated; glycosylation affects enzyme activity.", "mechanism": "LCAT dysfunction may contribute to lowered LDL-c in ACLF.", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "causal", "source_pmcid": "PMC12144760" }, { "confidence": "medium", "disease": "Hypoproteinemia", "glycan_involvement": "Albumin glycosylation may affect stability and function.", "mechanism": "Low ALB reflects hypoproteinemia, which worsens HBV-ACLF prognosis.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12144760" }, { "confidence": "high", "disease": "Hepatitis B virus infection (HBV)", "glycan_involvement": "HBsAg is a glycosylated viral envelope protein; glycosylation is essential for secretion and immune recognition.", "mechanism": "HBsAg positivity indicates chronic HBV infection and carrier status.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Pre-eclampsia (PE)", "glycan_involvement": "HBeAg is glycosylated, which may affect immune modulation and placental interaction.", "mechanism": "HBeAg promotes placental inflammation via TLR2 pathway, increasing risk of fetal rejection and PE.", "protein": "HBeAg", "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "NTCP is a glycosylated transporter; glycosylation affects its membrane localization and function.", "mechanism": "HBV infection inhibits NTCP, impairing bile acid transport and promoting cholestasis.", "protein": "NTCP", "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "FXR activity is modulated by glycoprotein interactions; glycosylation may affect receptor stability.", "mechanism": "Reduced FXR expression in GDM impairs bile acid metabolism, exacerbating cholestasis.", "protein": "FXR", "protein_enriched": { "function": "Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in", "gene_name": "NR1H4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96RI1" }, "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "high", "disease": "Macrosomia", "glycan_involvement": "Insulin is glycosylated; glycosylation affects its stability and receptor binding.", "mechanism": "Maternal hyperglycemia leads to fetal hyperinsulinemia, promoting fetal overgrowth.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "TNF glycosylation modulates its secretion and bioactivity.", "mechanism": "HBV infection increases TNF, promoting insulin resistance and GDM development.", "protein": "TNF", "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "IL-2 glycosylation affects receptor binding and immune signaling.", "mechanism": "HBV infection elevates IL-2, contributing to inflammatory milieu and insulin resistance.", "protein": "IL-2", "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "medium", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "Ferritin glycosylation influences its stability and serum levels.", "mechanism": "Elevated ferritin in HBV infection reflects inflammation, associated with increased GDM risk.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144766" }, { "confidence": "high", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "Glycosylation of HBsAg affects immune response and viral persistence.", "mechanism": "HBV carrier status increases risk of GDM via hepatic insulin resistance and inflammation.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "causal", "source_pmcid": "PMC12144766" }, { "confidence": "high", "disease": "Hepatitis B virus infection (HBV)", "glycan_involvement": "NTCP glycosylation modulates HBV entry efficiency.", "mechanism": "NTCP is the entry receptor for HBV; its glycosylation is essential for viral binding.", "protein": "NTCP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144766" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation of CD47 is essential for its recognition and function.", "mechanism": "CD47 on exosome surface acts as a 'don't eat me' signal, reducing clearance by phagocytes and enhancing exosome circulation for drug delivery.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects exosome sorting and stability.", "mechanism": "CD63 is a marker for exosome identification and purity, used to track exosome biodistribution and therapeutic efficacy.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates exosome membrane interactions.", "mechanism": "CD81 is used for exosome characterization and may influence targeting and uptake.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144782" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation critical for antigen presentation.", "mechanism": "Exosomes from dendritic cells present MHC I, enabling delivery of neoantigens for cancer immunotherapy.", "protein": "MHC I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for immune recognition.", "mechanism": "Exosomal MHC II enables immune activation and potential vaccine strategies against cancer.", "protein": "MHC II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "MET glycosylation affects receptor stability and signaling.", "mechanism": "Exosomes depleted of MET via siRNA reduce tumor angiogenesis and invasiveness.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Glycosylation modulates drug efflux activity.", "mechanism": "Exosome-mediated delivery of paclitaxel overcomes drug resistance in P-glycoprotein-positive PDAC cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for CD47 function.", "mechanism": "Bone marrow niche-derived exosomes with CD47 promote tumor dormancy and anti-tumor effects.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "protective", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Wound healing (related to cancer therapy)", "glycan_involvement": "Glycosylation influences exosome stability and function.", "mechanism": "MSC-derived exosomes with high CD63 expression enhance angiogenesis and wound healing.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation required for CD47-mediated immune evasion.", "mechanism": "Exosomes engineered for high CD47 expression improve delivery and retention of therapeutic agents in HCC models.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144782" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "GPR56 is a glycoprotein; glycosylation may affect receptor function and ligand interactions.", "mechanism": "Suppresses hepatocyte pyroptosis and ECM synthesis by inhibiting NF-\u03baB pathway, reducing HSC activation.", "protein": "GPR56 (ADGRG1)", "protein_enriched": { "function": "Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions (PubMed:39389061). Ligand binding cau", "gene_name": "ADGRG1", "glycan_count": 30, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G57321FI", "G07246CJ", "G29545VG", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G80479JV", "G83460ZZ", "G93718GY", "G00912UN", "G04657PL", "G08918WF", "G13131HA", "G20210JR", "G23984SE", "G27058EU", "G41071NU", "G70232NH", "G75983OB", "G83229XP", "G85282JO", "G90382BL" ], "uniprot_id": "Q9Y653" }, "relationship_type": "protective", "source_pmcid": "PMC12144805" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may influence GPR56 stability and detection.", "mechanism": "Upregulated in cirrhotic liver; high diagnostic accuracy (AUC=0.895) for cirrhosis.", "protein": "GPR56 (ADGRG1)", "protein_enriched": { "function": "Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions (PubMed:39389061). Ligand binding cau", "gene_name": "ADGRG1", "glycan_count": 30, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G57321FI", "G07246CJ", "G29545VG", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G80479JV", "G83460ZZ", "G93718GY", "G00912UN", "G04657PL", "G08918WF", "G13131HA", "G20210JR", "G23984SE", "G27058EU", "G41071NU", "G70232NH", "G75983OB", "G83229XP", "G85282JO", "G90382BL" ], "uniprot_id": "Q9Y653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144805" }, { "confidence": "high", "disease": "Hepatocyte pyroptosis", "glycan_involvement": "Glycosylation may modulate GPR56 signaling.", "mechanism": "Inhibits NLRP3 inflammasome activation and downstream pyroptosis in hepatocytes.", "protein": "GPR56 (ADGRG1)", "protein_enriched": { "function": "Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions (PubMed:39389061). Ligand binding cau", "gene_name": "ADGRG1", "glycan_count": 30, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G57321FI", "G07246CJ", "G29545VG", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G80479JV", "G83460ZZ", "G93718GY", "G00912UN", "G04657PL", "G08918WF", "G13131HA", "G20210JR", "G23984SE", "G27058EU", "G41071NU", "G70232NH", "G75983OB", "G83229XP", "G85282JO", "G90382BL" ], "uniprot_id": "Q9Y653" }, "relationship_type": "protective", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Hepatic stellate cell activation", "glycan_involvement": "Glycosylation may affect GPR56-mediated cell-cell communication.", "mechanism": "Reduces paracrine activation of HSCs by limiting hepatocyte pyroptosis-derived signals.", "protein": "GPR56 (ADGRG1)", "protein_enriched": { "function": "Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions (PubMed:39389061). Ligand binding cau", "gene_name": "ADGRG1", "glycan_count": 30, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G57321FI", "G07246CJ", "G29545VG", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G80479JV", "G83460ZZ", "G93718GY", "G00912UN", "G04657PL", "G08918WF", "G13131HA", "G20210JR", "G23984SE", "G27058EU", "G41071NU", "G70232NH", "G75983OB", "G83229XP", "G85282JO", "G90382BL" ], "uniprot_id": "Q9Y653" }, "relationship_type": "protective", "source_pmcid": "PMC12144805" }, { "confidence": "high", "disease": "Hepatocyte pyroptosis", "glycan_involvement": "NLRP3 is a glycoprotein; glycosylation may affect inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation triggers caspase-1-dependent pyroptosis.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Hepatocyte pyroptosis", "glycan_involvement": "Glycosylation may influence GSDMD processing.", "mechanism": "Cleaved GSDMD forms membrane pores, executing pyroptosis.", "protein": "GSDMD", "relationship_type": "causal", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Hepatocyte pyroptosis", "glycan_involvement": "Caspase-1 is glycosylated; modification may affect activity.", "mechanism": "Activates GSDMD and processes IL-1\u03b2/IL-18 during pyroptosis.", "protein": "Caspase-1", "relationship_type": "causal", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Inflammatory response", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Released during pyroptosis, drives inflammation and fibrosis.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Extracellular matrix accumulation", "glycan_involvement": "Collagen glycosylation affects fibril formation.", "mechanism": "Major ECM protein upregulated during fibrosis.", "protein": "COL1A1", "relationship_type": "causal", "source_pmcid": "PMC12144805" }, { "confidence": "medium", "disease": "Hepatic stellate cell activation", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Marker of activated HSCs, correlates with fibrosis severity.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12144805" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation shields epitopes, affects immune evasion and drug binding.", "mechanism": "Spike mediates viral entry via ACE2; targeted by fusion inhibitors and antibodies.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Heavy glycosylation modulates immune recognition and entry.", "mechanism": "Glycoprotein mediates host cell entry; targeted by berbamine hydrochloride.", "protein": "Ebola virus glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "Glycosylation affects enzyme activity and inhibitor binding.", "mechanism": "Neuraminidase cleaves sialic acids for viral release; targeted by inhibitors (e.g., Vitisin B).", "protein": "Influenza A virus Neuraminidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense N-glycosylation forms 'glycan shield', modulates immune evasion.", "mechanism": "gp120 mediates CD4 binding and entry; target for antiretrovirals and antibodies.", "protein": "HIV-1 Envelope glycoprotein gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "Limited glycosylation; assembly and immune recognition affected.", "mechanism": "Core protein essential for viral assembly; targeted by hydrophobic tagging-based degraders.", "protein": "HBV Core protein", "protein_enriched": { "function": "The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and proc", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6F5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "Herpes simplex virus 1 infection", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "gD mediates entry via host receptors; targeted by antiviral compounds.", "protein": "Herpes Simplex Virus 1 glycoprotein D", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04490" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "Lassa fever", "glycan_involvement": "Glycosylation affects entry and immune recognition.", "mechanism": "Glycoprotein mediates host cell entry; capsaicin inhibits entry.", "protein": "Lassa virus glycoprotein", "protein_enriched": { "function": "Seems to possess an anti-inflammatory activity as it can reverse the barrier-decreasing effects of TNF alpha. Might therefore contribute to the lack of inflammatory reaction seen during infection in s", "gene_name": "GP", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q66800" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Nucleocapsid essential for RNA packaging; targeted for degradation by ciclopirox.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "Viral infections (general)", "glycan_involvement": "O-glycosylation modulates filament formation and viral interaction.", "mechanism": "Vimentin facilitates viral infection; restricted by interferon-induced MXB protein.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "causal", "source_pmcid": "PMC12144950" }, { "confidence": "medium", "disease": "Viral infections (general)", "glycan_involvement": "No direct glycan involvement.", "mechanism": "MXB restricts vimentin-dependent viral infection.", "protein": "MXB protein", "relationship_type": "protective", "source_pmcid": "PMC12144950" }, { "confidence": "high", "disease": "Colon adenocarcinoma", "glycan_involvement": "CD39 is a glycoprotein; glycosylation affects its stability and cell surface localization.", "mechanism": "CD39 degrades ATP to AMP, promoting immunosuppressive adenosine accumulation and suppressing anti-tumor immunity.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Colon adenocarcinoma", "glycan_involvement": "CD73 is a glycoprotein; glycosylation is essential for its enzymatic activity and surface expression.", "mechanism": "CD73 converts AMP to adenosine, facilitating immunosuppression in the tumor microenvironment.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Immunosuppressive tumor microenvironment", "glycan_involvement": "Glycosylation modulates CD39 function and stability.", "mechanism": "Overexpression of CD39 correlates with increased Tregs and M2 macrophages, driving immunosuppression.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "causal", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Tumor immune exhaustion", "glycan_involvement": "Surface glycosylation may affect immune cell interactions.", "mechanism": "CD39+ CD8+ T cells are associated with immune exhaustion and poor anti-tumor response.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Colon adenocarcinoma", "glycan_involvement": "PD-L1 glycosylation regulates its stability and immune evasion.", "mechanism": "PD-L1 inhibits T cell activation; blockade enhances anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12144982" }, { "confidence": "medium", "disease": "Tumor immune exhaustion", "glycan_involvement": "TIM-3 is glycosylated; glycosylation affects ligand binding.", "mechanism": "TIM-3 expression correlates with CD39 and immune exhaustion markers.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144982" }, { "confidence": "medium", "disease": "Colon adenocarcinoma", "glycan_involvement": "CRT is glycosylated; glycosylation may affect its immunogenicity.", "mechanism": "CRT exposure on dying tumor cells signals immunogenic cell death and promotes dendritic cell maturation.", "protein": "Calreticulin (CRT)", "protein_enriched": { "function": "Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with a", "gene_name": "CALR", "glycan_count": 39, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G18647XP", "G22572EH", "G23453IV", "G23719VF", "G25079LO", "G31852PQ", "G33416PL", "G36379GD", "G39188ZX", "G41247ZX", "G46503DX", "G49874UX", "G51653BI", "G57317CE", "G57776ZU", "G59924QI", "G60145BJ", "G62765YT", "G64527OM", "G70101JE", "G72787SB", "G74724QE", "G76295SF", "G77547TA", "G80920RR", "G83460ZZ", "G83633GK", "G90575OW", "G92050GC", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G57321FI" ], "uniprot_id": "P27797" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144982" }, { "confidence": "medium", "disease": "Colon adenocarcinoma", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans; glycosylation is central to its function.", "mechanism": "Galectin-3 on tumor cell membranes mediates homotypic targeting of nanoparticles.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12144982" }, { "confidence": "medium", "disease": "Colon adenocarcinoma", "glycan_involvement": "E-cadherin is heavily glycosylated; glycosylation modulates adhesion.", "mechanism": "E-cadherin on tumor cell membranes facilitates nanoparticle targeting via cell adhesion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Tumor progression", "glycan_involvement": "Glycosylation is required for CD73 enzymatic activity.", "mechanism": "CD73-mediated adenosine production promotes tumor growth and immune evasion.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12144982" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "CFTR is a glycoprotein; glycosylation affects its folding and trafficking", "mechanism": "mRNA therapy restores functional CFTR protein in lung epithelial cells", "protein": "CFTR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated; glycans modulate immune recognition", "mechanism": "mRNA vaccines encode spike protein to induce protective immunity", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Nucleocapsid protein is glycosylated, influencing viral assembly", "mechanism": "siRNA targets nucleocapsid protein to inhibit viral replication", "protein": "Respiratory syncytial virus nucleocapsid protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Idiopathic pulmonary fibrosis", "glycan_involvement": "IL-11 is glycosylated; glycosylation affects secretion and stability", "mechanism": "siRNA silences IL-11 to reduce fibrotic signaling", "protein": "Interleukin-11", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "KRAS is farnesylated and may be glycosylated; glycosylation can affect localization", "mechanism": "siRNA targets mutant KRAS to inhibit tumor growth", "protein": "KRAS", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Idiopathic pulmonary fibrosis", "glycan_involvement": "MMP13 is glycosylated; glycans regulate enzyme activity", "mechanism": "mRNA delivery of MMP13 and KGF reverses fibrosis by remodeling ECM", "protein": "Matrix metalloproteinase-13 (MMP13)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "high", "disease": "Influenza A (H1N1)", "glycan_involvement": "Haemagglutinin is glycosylated; glycans shield antigenic sites", "mechanism": "mRNA vaccines encode haemagglutinin to induce immunity", "protein": "Haemagglutinin (Influenza A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "TSLP is glycosylated; glycosylation affects receptor binding", "mechanism": "siRNA silences TSLP to reduce airway inflammation", "protein": "Thymic stromal lymphopoietin (TSLP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "LPS-induced lung injury", "glycan_involvement": "MyD88 is glycosylated; glycosylation modulates signaling", "mechanism": "siRNA inhibits MyD88 to attenuate inflammatory response", "protein": "Myeloid differentiation factor 88 (MyD88)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "ENaC is glycosylated; glycosylation affects channel function", "mechanism": "ASO induces degradation of SCNN1A mRNA to reduce sodium absorption", "protein": "ENaC alpha subunit (SCNN1A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145032" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantigen targeted by immune system, leading to demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12145100" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IgG glycosylation modulates effector function and inflammation.", "mechanism": "Elevated serum IgG reflects ongoing autoimmune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145100" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IL-17A is glycosylated, which may affect secretion/stability.", "mechanism": "Pro-inflammatory cytokine produced by Th17 cells; promotes CNS inflammation.", "protein": "Interleukin-17A (IL-17A)", "relationship_type": "causal", "source_pmcid": "PMC12145100" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "TGF-\u03b21 glycosylation affects receptor binding and activity.", "mechanism": "Regulates Th17/Treg differentiation; imbalance contributes to disease.", "protein": "Transforming growth factor beta 1 (TGF-\u03b21)", "relationship_type": "regulatory", "source_pmcid": "PMC12145100" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may influence IL-10 stability and function.", "mechanism": "Anti-inflammatory cytokine secreted by Tregs; suppresses neuroinflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12145100" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Foxp3 is glycosylated; modification may affect nuclear localization.", "mechanism": "Master regulator of Treg development; loss leads to immune dysregulation.", "protein": "Forkhead box P3 (Foxp3)", "relationship_type": "regulatory", "source_pmcid": "PMC12145100" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may modulate protein stability.", "mechanism": "Drives Th17 differentiation; upregulation promotes inflammation.", "protein": "Retinoic acid receptor-related orphan receptor gamma t (ROR\u03b3t)", "protein_enriched": { "function": "Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular diff", "gene_name": "RORC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51449" }, "relationship_type": "causal", "source_pmcid": "PMC12145100" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "iNOS is glycosylated, which may affect localization.", "mechanism": "Marker of neuroinflammation; upregulated in activated glia.", "protein": "Inducible Nitric Oxide Synthase (iNOS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145100" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Associated with anti-inflammatory (M2) microglia/macrophages.", "protein": "Arginase-1 (Arg-1)", "protein_enriched": { "function": "Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathway", "gene_name": "ARG1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05089" }, "relationship_type": "protective", "source_pmcid": "PMC12145100" }, { "confidence": "low", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "PPAR-\u03b3 glycosylation may influence nuclear translocation.", "mechanism": "Regulates lipid metabolism and anti-inflammatory responses in CNS.", "protein": "Peroxisome proliferator-activated receptor gamma (PPAR-\u03b3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145100" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "IL-13 is a glycoprotein; glycosylation may affect secretion and receptor binding.", "mechanism": "IL-13 promotes type 2 inflammation, airway remodeling, and mucus production.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Mild Asthma", "glycan_involvement": "Glycosylation may modulate cytokine stability and receptor interaction.", "mechanism": "IL-13 R130Q (Q allele) increases risk of mild asthma twofold.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "risk allele", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Severe Asthma", "glycan_involvement": "No direct evidence for glycan modification impact on severity in this study.", "mechanism": "IL-13 QQ genotype is protective; QR genotype and R allele increase risk of severity.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "protective/risk allele", "source_pmcid": "PMC12145107" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation may affect secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes airway inflammation, hyperresponsiveness, and recruits neutrophils/eosinophils.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12145107" }, { "confidence": "high", "disease": "Mild Asthma", "glycan_involvement": "Glycosylation may modulate cytokine activity.", "mechanism": "TNF-\u03b1 \u2212308 GG genotype increases risk of mild asthma twofold.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "risk allele", "source_pmcid": "PMC12145107" }, { "confidence": "high", "disease": "Severe Asthma", "glycan_involvement": "Glycosylation may affect TNF-\u03b1 trimerization and receptor interaction.", "mechanism": "TNF-\u03b1 \u2212308 GG genotype increases risk of severe asthma three- to sixfold; G allele also increases risk.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "risk allele/independent predictor", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Severe Asthma", "glycan_involvement": "Glycosylation status may influence therapeutic efficacy.", "mechanism": "Targeting TNF-\u03b1 activity may reduce glucocorticosteroid dependence in severe asthma.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Allergic Rhinitis", "glycan_involvement": "Glycosylation may affect cytokine function.", "mechanism": "IL-13 polymorphisms associated with allergic traits and elevated IgE.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Nasal Polyposis", "glycan_involvement": "Glycosylation may modulate cytokine activity.", "mechanism": "IL-13 contributes to type 2 inflammation, a feature of nasal polyposis.", "protein": "Interleukin-13 (IL-13)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Nasal Polyposis", "glycan_involvement": "Glycosylation may affect cytokine secretion.", "mechanism": "TNF-\u03b1 is implicated in airway inflammation and comorbid nasal polyposis in severe asthma.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12145107" }, { "confidence": "medium", "disease": "Lead poisoning", "glycan_involvement": "Albumin glycosylation may affect its binding and detoxification capacity.", "mechanism": "Lead toxicity decreases serum albumin; zeolite reverses this effect.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation modulates catalase stability and activity.", "mechanism": "Zeolite increases catalase activity, reducing oxidative stress induced by lead.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12145127" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation affects enzyme localization and function.", "mechanism": "Zeolite enhances superoxide dismutase activity, mitigating lead-induced ROS.", "protein": "Superoxide dismutase", "relationship_type": "protective", "source_pmcid": "PMC12145127" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation influences enzyme activity and cellular protection.", "mechanism": "Zeolite increases glutathione peroxidase activity, counteracting lead toxicity.", "protein": "Glutathione peroxidase", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such ", "gene_name": "GPX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07203" }, "relationship_type": "protective", "source_pmcid": "PMC12145127" }, { "confidence": "medium", "disease": "Lead poisoning", "glycan_involvement": "Glycosylation can affect hemoglobin stability and erythrocyte lifespan.", "mechanism": "Lead poisoning reduces hemoglobin; zeolite may restore levels.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "low", "disease": "Multiorgan damage", "glycan_involvement": "Glycosylation modulates enzyme secretion and activity.", "mechanism": "ALT elevation indicates liver injury in lead poisoning; zeolite may lower ALT.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "low", "disease": "Multiorgan damage", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "AST elevation reflects organ damage from lead; zeolite may reduce AST.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may influence albumin's binding properties.", "mechanism": "Increased binding of 4-hydroxynonenal to albumin after zeolite treatment in cancer models.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation impacts catalase function in neural tissue.", "mechanism": "Zeolite alleviates oxidative stress and plaque accumulation via catalase activation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12145127" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation may modulate albumin's neuroprotective roles.", "mechanism": "Albumin binding to oxidative stress markers increased after zeolite treatment.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145127" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation affects stability and detection sensitivity.", "mechanism": "Released into blood upon cardiomyocyte injury; standard diagnostic marker for AMI.", "protein": "Troponin T (cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12145150" }, { "confidence": "high", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation modulates plasma half-life and immunoreactivity.", "mechanism": "Released during myocardial injury; used for AMI diagnosis.", "protein": "Troponin I (cTnI)", "relationship_type": "biomarker", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Heavily glycosylated; glycan moieties mediate immune cell interactions.", "mechanism": "Regulated by miRNAs; involved in inflammatory response post-MI.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "causal", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation required for ligand binding and cell trafficking.", "mechanism": "Targeted by M2 macrophage-derived EVs; reduces monocyte recruitment and promotes repair.", "protein": "CCR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Ischemia-Reperfusion Injury", "glycan_involvement": "N-glycosylation critical for membrane localization and function.", "mechanism": "Regulated by miR-92a; enhances autophagy and energy metabolism in cardiac cells.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "protective", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Ischemia-Reperfusion Injury", "glycan_involvement": "Glycosylation affects transporter activity.", "mechanism": "Regulated by miR-92a; involved in lipid transport and energy metabolism.", "protein": "Abca8b", "relationship_type": "protective", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Acute Myocardial Infarction (AMI)", "glycan_involvement": "Glycosylation modulates protein stability.", "mechanism": "Targeted by miR-124-3p; promotes cardiac repair and protection.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "protective", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "O-glycosylation influences nuclear translocation.", "mechanism": "Negatively regulated by miRNAs; controls inflammatory response after MI.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates kinase activity.", "mechanism": "Regulated by miRNAs; involved in post-MI inflammatory signaling.", "protein": "MAPK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145150" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation required for receptor binding.", "mechanism": "Regulated by miRNAs; modulates immune response in ACS.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145150" }, { "confidence": "high", "disease": "NSTE-ACS", "glycan_involvement": "CTRP5 is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Elevated serum CTRP5 correlates with presence and severity of NSTE-ACS.", "protein": "CTRP5", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation enables CTRP5's extracellular function.", "mechanism": "Serum CTRP5 increases with number of affected coronary vessels and SYNTAX II score.", "protein": "CTRP5", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "Myocardial fibrosis (MF)", "glycan_involvement": "Glycosylation supports CTRP5's stability and activity in ECM remodeling.", "mechanism": "Higher CTRP5 levels associate with increased MF (LGE-positive, high PCI/PCIII).", "protein": "CTRP5", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for CTRP5's receptor interactions.", "mechanism": "CTRP5 promotes monocyte/macrophage phenotypic switching, LDL-C oxidation, and vascular smooth muscle cell activation.", "protein": "CTRP5", "relationship_type": "causal", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "Myocardial fibrosis (MF)", "glycan_involvement": "Glycosylation affects procollagen folding and secretion.", "mechanism": "Serum PCI levels rise after myocardial infarction, reflecting collagen synthesis and fibrosis.", "protein": "PCI", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "Myocardial fibrosis (MF)", "glycan_involvement": "Glycosylation necessary for procollagen III maturation.", "mechanism": "Serum PCIII levels increase post-infarction, indicating active fibrosis.", "protein": "PCIII", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "NSTEMI (subset of NSTE-ACS)", "glycan_involvement": "Glycosylation maintains CTRP5's bioactivity.", "mechanism": "CTRP5 levels are higher in NSTEMI than unstable angina, reflecting greater inflammation and tissue injury.", "protein": "CTRP5", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation may influence CTRP5's receptor binding and downstream signaling.", "mechanism": "CTRP5 modulates TGF-\u03b2, Notch1, and Hedgehog signaling in vascular cells, suggesting a role in disease progression.", "protein": "CTRP5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145151" }, { "confidence": "medium", "disease": "Myocardial fibrosis (MF)", "glycan_involvement": "Glycosylation impacts CTRP5's interaction with ECM components.", "mechanism": "CTRP5's regulation of fibroblast activation and ECM remodeling may be targetable for anti-fibrotic therapy.", "protein": "CTRP5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145151" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for CTRP5's localization and function.", "mechanism": "CTRP5 is elevated in atherosclerotic arteries and localizes to macrophages and smooth muscle cells.", "protein": "CTRP5", "relationship_type": "biomarker", "source_pmcid": "PMC12145151" }, { "confidence": "high", "disease": "Aged/aging skin", "glycan_involvement": "CD44 is a glycoprotein receptor for hyaluronic acid; glycosylation affects ligand binding and cell signaling.", "mechanism": "Reduced CD44 glycoprotein levels impair keratinocyte proliferation and hyaluronic acid regulation, leading to decreased epidermal regeneration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "medium", "disease": "Aged/aging skin", "glycan_involvement": "Fibrinogen glycosylation modulates clot formation and stability.", "mechanism": "Elevated fibrinogen levels and altered glycosylation in aging disrupt hemostasis, contributing to impaired wound healing.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "medium", "disease": "Chronic wounds", "glycan_involvement": "Glycosylation affects fibronectin's matrix assembly and cell adhesion.", "mechanism": "Fibronectin is secreted during hemostasis and forms part of the provisional matrix; its deficiency or altered glycosylation impairs wound healing.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145203" }, { "confidence": "low", "disease": "Chronic wounds", "glycan_involvement": "Glycosylation modulates thrombospondin's interactions with ECM and cells.", "mechanism": "Thrombospondin is released during hemostasis; altered levels or glycosylation may reflect impaired healing.", "protein": "Thrombospondin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145203" }, { "confidence": "medium", "disease": "Aged/aging skin", "glycan_involvement": "N-glycosylation critical for vWF function in platelet adhesion.", "mechanism": "Secreted during hemostasis; altered glycosylation or levels may contribute to age-related changes in clotting and wound healing.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC12145203" }, { "confidence": "high", "disease": "Aged/aging skin", "glycan_involvement": "Glycosaminoglycan chains are essential for water retention and cell signaling.", "mechanism": "Reduced proteoglycan content in aged skin leads to impaired ECM structure and delayed wound healing.", "protein": "Proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "high", "disease": "Aged/aging skin", "glycan_involvement": "GAGs are glycan chains on proteoglycans; their abundance and structure are critical for ECM function.", "mechanism": "Decline in GAGs, including hyaluronic acid, delays inflammation and reduces skin elasticity and hydration.", "protein": "Glycosaminoglycans (GAGs)", "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "high", "disease": "Aged/aging skin", "glycan_involvement": "Collagen glycosylation affects fiber assembly and ECM integrity.", "mechanism": "Non-enzymatic glycation and altered glycosylation of collagen in aging leads to disorganized fibers and impaired wound closure.", "protein": "Collagen (glycosylated forms)", "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "medium", "disease": "Chronic wounds", "glycan_involvement": "Glycosylation may regulate MMP secretion and activity.", "mechanism": "Chronic overactivity of MMPs, possibly influenced by glycosylation, leads to ECM degradation and impaired wound resolution.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "CD44 glycosylation modulates HA binding and cell migration.", "mechanism": "Reduced CD44 and hyaluronic acid interaction impairs keratinocyte migration and wound healing in diabetic skin.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12145203" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "GLP-1R is a glycoprotein receptor; glycosylation affects receptor function and ligand binding.", "mechanism": "GLP-1R agonists improve glycemic control and reduce body weight.", "protein": "GLP-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145500" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates receptor signaling in hepatic tissue.", "mechanism": "GLP-1R agonists improve fatty liver markers but have limited effect on fibrosis.", "protein": "GLP-1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145500" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "GIPR glycosylation influences receptor trafficking and signaling.", "mechanism": "Tirzepatide (GIP/GLP-1RA) activation of GIPR improves insulin sensitivity and reduces hepatic steatosis.", "protein": "GIPR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145500" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "hsCRP is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "hsCRP levels indicate systemic inflammation; reduction reflects anti-inflammatory effect of tirzepatide.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12145500" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects long-term glycemic control; reduction indicates improved diabetes management.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12145500" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Lipoproteins are glycosylated; glycan structures affect lipid transport and metabolism.", "mechanism": "Elevated TG-rich lipoproteins contribute to hepatic steatosis; tirzepatide reduces TG levels.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12145500" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Albumin glycosylation affects renal filtration and biomarker accuracy.", "mechanism": "Urine albumin-to-creatinine ratio (UACR) is a marker of renal damage; reduction indicates nephropathy improvement.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145500" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet glycoproteins are heavily glycosylated, influencing platelet function.", "mechanism": "Platelet count is part of FIB-4 index for fibrosis assessment.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12145500" }, { "confidence": "medium", "disease": "MASLD/MASH", "glycan_involvement": "Both are glycoprotein enzymes; glycosylation affects stability and activity.", "mechanism": "AST and ALT levels are markers of liver injury; reduction reflects improvement.", "protein": "AST/ALT", "relationship_type": "biomarker", "source_pmcid": "PMC12145500" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Receptor glycosylation modulates cardiovascular signaling pathways.", "mechanism": "GLP-1R agonists reduce cardiovascular risk markers (e.g., hsCRP, leptin).", "protein": "GLP-1R", "relationship_type": "protective", "source_pmcid": "PMC12145500" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Low ceruloplasmin levels reflect impaired copper transport due to ATP7B mutation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation required for ceruloplasmin secretion; defects may exacerbate disease.", "mechanism": "Defective ATP7B impairs ceruloplasmin copper loading, leading to copper accumulation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "causal", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Albumin glycosylation may affect half-life and function.", "mechanism": "Low serum albumin indicates impaired liver synthetic function in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "Glycosylation status not specified; serum enzymes may be glycosylated.", "mechanism": "Elevated transaminases reflect hepatocellular injury; unstable patterns predict poor prognosis.", "protein": "Transaminases (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Liver fibrosis progression", "glycan_involvement": "Not specified.", "mechanism": "Persistent elevation associated with fibrosis progression.", "protein": "Transaminases (AST/ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "low", "disease": "Liver cancer", "glycan_involvement": "Glycosylation may affect detection and function.", "mechanism": "Altered ceruloplasmin levels may reflect advanced liver disease and risk of malignancy.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Platelet surface glycoproteins mediate clearance and function.", "mechanism": "Low platelet count (reflecting portal hypertension) predicts unfavorable outcome in WD.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "Glycosylation required for ceruloplasmin stability and activity.", "mechanism": "Restoring ceruloplasmin function may improve copper homeostasis.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Liver fibrosis progression", "glycan_involvement": "Glycosylation may affect albumin turnover.", "mechanism": "Low albumin at 1 year predicts unfavorable long-term outcome.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145598" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "Proper glycosylation ensures ceruloplasmin secretion and function.", "mechanism": "Normal ceruloplasmin levels associated with better copper transport and less hepatic injury.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "protective", "source_pmcid": "PMC12145598" }, { "confidence": "high", "disease": "Refractory Mycoplasma pneumoniae pneumonia (RMPP)", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP indicates strong inflammatory response and predicts RMPP severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "high", "disease": "Refractory Mycoplasma pneumoniae pneumonia (RMPP)", "glycan_involvement": "LDH glycosylation may influence serum half-life.", "mechanism": "High LDH levels reflect tissue damage and correlate with severe disease.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Refractory Mycoplasma pneumoniae pneumonia (RMPP)", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects clearance.", "mechanism": "Elevated D-dimer is associated with coagulation activation and severe pneumonia.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Severe Mycoplasma pneumoniae pneumonia (SMPP)", "glycan_involvement": "N-glycosylation modulates fibrinogen function and immune response.", "mechanism": "Fibrinogen elevation reflects systemic inflammation and risk of SMPP.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "Fc N-glycosylation regulates effector functions and inflammation.", "mechanism": "IgG response is essential for pathogen clearance.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "N-glycosylation affects IgM stability and complement activation.", "mechanism": "Early IgM response helps limit infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "Bacterial glycosylation may modulate host immune evasion.", "mechanism": "Bacterial glycoprotein adhesins mediate attachment to respiratory epithelium.", "protein": "Mycoplasma pneumoniae adhesins", "relationship_type": "causal", "source_pmcid": "PMC12145612" }, { "confidence": "high", "disease": "Severe Mycoplasma pneumoniae pneumonia (SMPP)", "glycan_involvement": "Glycosylation affects CRP's interaction with immune cells.", "mechanism": "High CRP levels correlate with SMPP severity and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "high", "disease": "Severe Mycoplasma pneumoniae pneumonia (SMPP)", "glycan_involvement": "Minor glycosylation may affect LDH serum levels.", "mechanism": "Elevated LDH is a marker of lung tissue injury in SMPP.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Pleural effusion", "glycan_involvement": "N-glycosylation modulates fibrinogen's inflammatory properties.", "mechanism": "Fibrinogen elevation is associated with pleural inflammation and effusion.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145612" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Hyperglycemia-induced glycosylation impairs cytokine production.", "mechanism": "Reduced IL-1 secretion by monocytes in diabetes impairs immune response, increasing infection risk.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Increased glycosylation inhibits cytokine production.", "mechanism": "Lower IL-6 secretion in diabetic monocytes reduces pathogen resistance.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Hyperglycemia increases glycosylation, reducing IL-10.", "mechanism": "Glycosylation inhibits IL-10 production by myeloid cells, weakening anti-inflammatory response.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Increased glycosylation in diabetes inhibits TNF secretion.", "mechanism": "Glycosylation reduces TNF production by T cells, impairing immune defense.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "low", "disease": "Postoperative infection", "glycan_involvement": "Hyperglycemia-induced glycosylation inhibits interferon secretion.", "mechanism": "Glycosylation reduces interferon production, compromising adaptive immunity.", "protein": "Interferon", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Glycosylation reduces MHC I expression.", "mechanism": "Reduced MHC I expression on myeloid cells impairs antigen presentation and immune response.", "protein": "Class I Major Histocompatibility Complex (MHC I)", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "low", "disease": "Postoperative infection", "glycan_involvement": "Indirect; hyperglycemia affects enzyme function, possibly via glycation.", "mechanism": "Hyperglycemia inhibits G6PD, increasing leukocyte apoptosis and impairing antibacterial function.", "protein": "Glucose-6-phosphate dehydrogenase (G6PD)", "protein_enriched": { "function": "Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to ", "gene_name": "G6PD", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11413" }, "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "medium", "disease": "Postoperative infection", "glycan_involvement": "Altered glycosylation affects leukocyte function.", "mechanism": "Diabetes impairs leukocyte adhesion, chemotaxis, and phagocytosis, increasing infection risk.", "protein": "Polymorphonuclear leukocyte surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "low", "disease": "Low postoperative survival", "glycan_involvement": "Glycosylation inhibits cytokine production.", "mechanism": "Impaired IL-1 response in diabetes may contribute to poor long-term outcomes.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12145621" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Glycosylation reduces MHC I expression.", "mechanism": "Reduced MHC I expression impairs adaptive immunity, increasing sepsis risk.", "protein": "Class I Major Histocompatibility Complex (MHC I)", "relationship_type": "causal", "source_pmcid": "PMC12145621" }, { "confidence": "high", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "Glycosylation of F protein is critical for its function and cell entry.", "mechanism": "Mutations in the F protein glycoprotein increase neurovirulence and allow measles virus to enter neurons and persist in the CNS.", "protein": "Measles virus F protein", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "Cox5a", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11240" }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "medium", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "Glycosylation may affect M protein function and viral assembly.", "mechanism": "Mutations in the M protein glycoprotein contribute to viral persistence and neurovirulence in SSPE.", "protein": "Measles virus M protein", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBAD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15164" }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation is essential for receptor binding and immune evasion.", "mechanism": "H protein mediates viral attachment to host cells, initiating infection.", "protein": "Measles virus H protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "high", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated measles-specific IgG in CSF is a diagnostic marker for SSPE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12145622" }, { "confidence": "medium", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "Glycosylation affects interferon alpha's stability and bioactivity.", "mechanism": "Used as an immunomodulatory therapy to reduce viral replication and inflammation in SSPE.", "protein": "Interferon alpha", "protein_enriched": { "function": "Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase", "gene_name": "IFNA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01562" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145622" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation is required for proper folding and function.", "mechanism": "F protein mediates membrane fusion and viral entry into host cells.", "protein": "Measles virus F protein", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "Cox5a", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11240" }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "medium", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "Glycosylation modulates receptor binding and immune recognition.", "mechanism": "Mutations in H protein may contribute to altered tropism and persistence in the CNS.", "protein": "Measles virus H protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation influences antibody effector functions.", "mechanism": "Neutralizing IgG antibodies confer immunity after vaccination or infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12145622" }, { "confidence": "medium", "disease": "Subacute sclerosing panencephalitis (SSPE)", "glycan_involvement": "Glycosylation sites may affect antibody accessibility.", "mechanism": "Targeted by neutralizing antibodies and antiviral therapies.", "protein": "Measles virus F protein", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "Cox5a", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11240" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145622" }, { "confidence": "low", "disease": "Measles", "glycan_involvement": "Glycosylation may regulate protein-protein interactions.", "mechanism": "M protein is essential for viral assembly and budding.", "protein": "Measles virus M protein", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBAD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15164" }, "relationship_type": "causal", "source_pmcid": "PMC12145622" }, { "confidence": "high", "disease": "Inflammatory liver disease", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "IL-6 is upregulated during liver inflammation and injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Inflammatory liver disease", "glycan_involvement": "NFKB1 is glycosylated; glycosylation may modulate its activity.", "mechanism": "NF-\u03baB mediates transcription of inflammatory cytokines in liver injury.", "protein": "Nuclear factor NF-kappa-B p105 subunit (NFKB1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation regulates secretion and receptor binding.", "mechanism": "TNF-\u03b1 is elevated in DILI and mediates hepatocyte apoptosis.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation modulates IL-6 bioactivity.", "mechanism": "IL-6 is elevated in DILI, reflecting inflammatory response.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Valproic acid-induced liver injury", "glycan_involvement": "Glycosylation may affect NF-\u03baB signaling.", "mechanism": "NF-\u03baB activation is associated with VPA-induced hepatic inflammation.", "protein": "Nuclear factor NF-kappa-B p105 subunit (NFKB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Valproic acid-induced liver injury", "glycan_involvement": "Glycosylation impacts IL-6 secretion.", "mechanism": "IL-6 expression is a marker of VPA-induced hepatic inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Oxidative stress-related liver damage", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 function.", "mechanism": "TNF-\u03b1 mediates inflammation and cell death in oxidative liver injury.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Oxidative stress-related liver damage", "glycan_involvement": "Glycosylation affects IL-6 stability.", "mechanism": "IL-6 is induced by oxidative stress in liver.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Oxidative stress-related liver damage", "glycan_involvement": "Glycosylation may modulate NF-\u03baB function.", "mechanism": "NF-\u03baB is activated by oxidative stress, promoting inflammation.", "protein": "Nuclear factor NF-kappa-B p105 subunit (NFKB1)", "relationship_type": "biomarker", "source_pmcid": "PMC12145642" }, { "confidence": "medium", "disease": "Valproic acid-induced liver injury", "glycan_involvement": "Glycosylation influences TNF-\u03b1 secretion.", "mechanism": "TNF-\u03b1 is upregulated in VPA-induced liver injury, promoting inflammation.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12145642" }, { "confidence": "high", "disease": "Chronic Liver Disease (CLD)", "glycan_involvement": "CD63 is a glycoprotein; glycosylation may affect sEV targeting and uptake", "mechanism": "CD63+ sEVs from apoptotic MSCs modulate immune response and reduce fibrosis", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation modulates receptor binding", "mechanism": "TGF-\u03b21 upregulation drives fibrogenesis; sEVs Apo suppress TGF-\u03b21 to reverse fibrosis", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Indirect; Smad2 interacts with glycoprotein TGF-\u03b21 pathway", "mechanism": "Phosphorylated Smad2 mediates TGF-\u03b2 signaling; sEVs Apo inhibit its activation", "protein": "Smad2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Indirect; Smad3 is downstream of glycoprotein TGF-\u03b21", "mechanism": "Phosphorylated Smad3 promotes ECM deposition; sEVs Apo inhibit its activation", "protein": "Smad3", "protein_enriched": { "function": "Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194).", "gene_name": "SMAD5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99717" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Indirect; modulates glycoprotein signaling", "mechanism": "Smad7 upregulation by sEVs Apo provides negative feedback to TGF-\u03b2/Smad signaling, reducing fibrosis", "protein": "Smad7", "relationship_type": "protective", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "CD206 is a glycoprotein; recognizes glycan motifs on sEVs", "mechanism": "sEVs Apo induce M2 macrophage polarization (CD206+), reducing inflammation", "protein": "CD206 (Mannose receptor)", "relationship_type": "protective", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Immune Disorders", "glycan_involvement": "Indirect; Treg function may be modulated by glycoprotein interactions", "mechanism": "sEVs Apo promote Treg (FOXP3+) induction, suppressing immune activation", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "protective", "source_pmcid": "PMC12145648" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "CD63 glycosylation may affect vesicle uptake", "mechanism": "MSC-derived apoptotic vesicles modulate liver macrophages and mitigate diabetes", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Hepatic Cirrhosis", "glycan_involvement": "TGF-\u03b21 glycosylation affects stability and signaling", "mechanism": "TGF-\u03b21 upregulation leads to collagen I deposition and cirrhosis; sEVs Apo reduce TGF-\u03b21", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12145648" }, { "confidence": "medium", "disease": "Lung Injury", "glycan_involvement": "CD206 recognizes glycan motifs on sEVs", "mechanism": "MSC-derived apoptotic sEVs induce M2 macrophages (CD206+), reducing lung inflammation", "protein": "CD206 (Mannose receptor)", "relationship_type": "protective", "source_pmcid": "PMC12145648" }, { "confidence": "high", "disease": "Getah virus infection", "glycan_involvement": "Envelope glycoprotein likely N-glycosylated, mediating host cell interaction.", "mechanism": "E1 glycoprotein forms heterodimers with E2, facilitating viral entry and assembly.", "protein": "E1", "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "high", "disease": "Getah virus infection", "glycan_involvement": "Envelope glycoprotein likely N-glycosylated, mediating host cell attachment.", "mechanism": "E2 glycoprotein forms heterodimers with E1, essential for viral infectivity.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "high", "disease": "Impaired innate immunity", "glycan_involvement": "No direct glycosylation involvement reported for Nsp2.", "mechanism": "Nsp2 suppresses IFN-\u03b2 production by inhibiting IRF3 activation and nuclear translocation.", "protein": "Nsp2", "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "medium", "disease": "Public health risk (potential zoonosis)", "glycan_involvement": "Glycosylation may affect host range and immune evasion.", "mechanism": "E1 glycoprotein enables cross-species transmission via envelope-mediated entry.", "protein": "E1", "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "medium", "disease": "Public health risk (potential zoonosis)", "glycan_involvement": "Glycosylation may modulate receptor binding and immune escape.", "mechanism": "E2 glycoprotein mediates host cell attachment, influencing zoonotic potential.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "high", "disease": "Getah virus infection", "glycan_involvement": "No glycosylation involvement.", "mechanism": "Nsp2 is essential for viral replication and immune evasion, making it a drug target.", "protein": "Nsp2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145652" }, { "confidence": "medium", "disease": "Fever in horses", "glycan_involvement": "Envelope glycoprotein glycosylation may influence virulence.", "mechanism": "E1 glycoprotein mediates viral entry, leading to infection and clinical symptoms.", "protein": "E1", "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "medium", "disease": "Reproductive disorders in pigs", "glycan_involvement": "Glycosylation may affect tissue tropism.", "mechanism": "E2 glycoprotein facilitates infection in pigs, causing reproductive symptoms.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "medium", "disease": "Fetal death in pigs", "glycan_involvement": "Glycosylation may modulate immune evasion in fetal tissues.", "mechanism": "E1 glycoprotein enables viral spread to fetal tissues.", "protein": "E1", "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "low", "disease": "Impaired innate immunity", "glycan_involvement": "N-glycosylation shields epitopes from immune recognition.", "mechanism": "E2 glycoprotein may contribute to immune evasion via glycan shielding.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC12145652" }, { "confidence": "high", "disease": "Echinocandin-resistant Candida glabrata infection", "glycan_involvement": "Disruption of \u03b2-glucan synthesis (a major fungal cell wall glycan).", "mechanism": "FKS gene mutations alter (1,3)-\u03b2-D-glucan synthase, conferring resistance to echinocandins.", "protein": "(1,3)-\u03b2-D-glucan synthase (Fks1/Fks2)", "relationship_type": "causal", "source_pmcid": "PMC12145744" }, { "confidence": "medium", "disease": "Bloodstream infection (BSI) due to Candida glabrata", "glycan_involvement": "Mannosylation critical for immune evasion.", "mechanism": "Cell wall mannoproteins mediate immune evasion and host interaction, facilitating bloodstream infection.", "protein": "Candida glabrata cell wall mannoproteins", "relationship_type": "causal", "source_pmcid": "PMC12145744" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI) due to Candida glabrata", "glycan_involvement": "Glycosylation enables adhesion to host tissues.", "mechanism": "Mannoproteins mediate adhesion to urinary tract surfaces, promoting colonization.", "protein": "Candida glabrata cell wall mannoproteins", "relationship_type": "causal", "source_pmcid": "PMC12145744" }, { "confidence": "high", "disease": "Urinary tract infection (UTI) due to Candida glabrata", "glycan_involvement": "Extracellular glycoproteins form biofilm matrix.", "mechanism": "Biofilm matrix glycoproteins facilitate biofilm formation on urinary stents, leading to persistent infection.", "protein": "Candida glabrata biofilm matrix glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12145744" }, { "confidence": "high", "disease": "Echinocandin-resistant Candida glabrata infection", "glycan_involvement": "Glycosylated matrix components enhance resistance.", "mechanism": "Biofilm matrix impedes antifungal penetration, increasing drug resistance.", "protein": "Candida glabrata biofilm matrix glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12145744" }, { "confidence": "high", "disease": "Bloodstream infection (BSI) due to Candida glabrata", "glycan_involvement": "Inhibition of \u03b2-glucan (glycan) synthesis.", "mechanism": "Targeted by echinocandins to inhibit cell wall synthesis.", "protein": "(1,3)-\u03b2-D-glucan synthase (Fks1/Fks2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145744" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI) due to Candida glabrata", "glycan_involvement": "Affects \u03b2-glucan content in cell wall.", "mechanism": "Targeted by echinocandins and amphotericin B to disrupt cell wall integrity.", "protein": "(1,3)-\u03b2-D-glucan synthase (Fks1/Fks2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145744" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 is N-glycosylated, which affects its stability and detection.", "mechanism": "PD-L1 expression on tumor cells predicts response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L2 is N-glycosylated, influencing its cell surface expression.", "mechanism": "High PD-L2 expression on MDSCs predicts poor response to pembrolizumab/trametinib therapy.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-1 glycosylation modulates ligand binding and immune signaling.", "mechanism": "PD-1 is targeted by pembrolizumab to block inhibitory signaling in T-cells.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12145753" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "CD4 is glycosylated, affecting T-cell activation and migration.", "mechanism": "Higher baseline CD4+ T-cell infiltration is associated with improved clinical outcomes.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective", "source_pmcid": "PMC12145753" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "CD8 glycosylation influences T-cell receptor interactions.", "mechanism": "Higher baseline CD8+ T-cell infiltration correlates with better response to therapy.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "protective", "source_pmcid": "PMC12145753" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "CD20 glycosylation affects B-cell function and survival.", "mechanism": "Higher baseline CD20+ B-cell infiltration is significantly associated with disease control.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "protective", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "Immune checkpoint inhibitor resistance", "glycan_involvement": "Glycosylation stabilizes PD-L2 on cell surface, enhancing immunosuppressive function.", "mechanism": "PD-L2 on MDSCs inhibits T-cell activation, contributing to resistance to pembrolizumab.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "causal", "source_pmcid": "PMC12145753" }, { "confidence": "medium", "disease": "KRAS-mutant NSCLC", "glycan_involvement": "KRAS signaling may influence PD-L1 glycosylation and expression.", "mechanism": "KRAS mutations can upregulate PD-L1 expression, impacting immunotherapy response.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "Progressive disease (PD)", "glycan_involvement": "N-glycosylation of PD-L2 affects its immunosuppressive activity.", "mechanism": "High frequency of PD-L2+ MDSCs at baseline predicts progression on therapy.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "Partial response (PR)/Stable disease (SD)", "glycan_involvement": "Reduced glycosylated PD-L2 on MDSCs may decrease immunosuppression.", "mechanism": "Low baseline PD-L2+ MDSCs are associated with clinical benefit from pembrolizumab/trametinib.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "protective", "source_pmcid": "PMC12145753" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylated N-glycans (especially \u03b12-6-linked) mediate virus binding and infection.", "mechanism": "Serve as principal receptors for viral attachment and entry.", "protein": "N-glycans", "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylated O-glycans (\u03b12-3 and \u03b12-6-linked) can act as functional receptors.", "mechanism": "Support all steps from primary binding to entry for some IAV strains.", "protein": "O-glycans", "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylated GSLs (especially neolacto-series) are utilized as receptors.", "mechanism": "Independently support virus binding and entry.", "protein": "Glycosphingolipids (GSLs)", "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylated N-glycans on LAMP1 mediate virus binding.", "mechanism": "Used as a model N-glycoprotein to study virus binding specificity.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145812" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylated O-glycans on GPa mediate virus binding.", "mechanism": "Used as a model O-glycoprotein to study virus binding specificity.", "protein": "Glycophorin A (GPa)", "relationship_type": "biomarker", "source_pmcid": "PMC12145812" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Heavily O-glycosylated, rich in sialylated O-glycans (especially \u03b12-3-linked).", "mechanism": "Act as decoy receptors in mucus, limiting infection.", "protein": "Mucins", "relationship_type": "protective", "source_pmcid": "PMC12145812" }, { "confidence": "medium", "disease": "Avian influenza", "glycan_involvement": "Sialylation by ST3Gal5 enables GM3 to act as a receptor.", "mechanism": "Supports efficient infection by avian H5N1 strains.", "protein": "Ganglioside GM3", "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "low", "disease": "Avian influenza", "glycan_involvement": "Sialylation by ST3Gal5 enables GM4 to act as a receptor.", "mechanism": "Likely supports infection by avian H5N1 strains.", "protein": "Ganglioside GM4", "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Recognizes \u03b12-3 or \u03b12-6-linked sialic acids on host glycoproteins/lipids.", "mechanism": "Viral glycoprotein mediating binding to sialylated glycoproteins/glycolipids.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Cleaves sialic acids, balancing HA binding and facilitating entry.", "mechanism": "Viral glycoprotein modulating receptor engagement and virus motility.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12145812" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "O-glycosylation affects CK18 stability and release during apoptosis.", "mechanism": "CK18-M30 is released during hepatocyte apoptosis, reflecting liver cell death and inflammation in MASH.", "protein": "Cytokeratin 18-M30", "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "O-glycosylation modulates CK18-M65 detection and release.", "mechanism": "CK18-M65 reflects total cell death (apoptosis and necrosis) in hepatocytes, correlating with MASH severity.", "protein": "Cytokeratin 18-M65", "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect ALT secretion and stability.", "mechanism": "ALT elevation indicates hepatocellular injury and correlates with liver fat reduction in MASLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may influence AST activity and release.", "mechanism": "AST elevation is associated with liver injury and steatosis in MASLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates GGT stability and serum levels.", "mechanism": "GGT is elevated in MASLD and reflects oxidative stress and hepatobiliary injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "O-glycosylation impacts CK18-M30 detection.", "mechanism": "CK18-M30 levels correlate with degree of steatosis and hepatocyte apoptosis.", "protein": "Cytokeratin 18-M30", "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "O-glycosylation affects CK18-M65 release.", "mechanism": "CK18-M65 levels reflect total hepatocyte death in steatosis.", "protein": "Cytokeratin 18-M65", "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may affect ALT serum stability.", "mechanism": "ALT is a marker of hepatocyte injury in steatosis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation influences GGT activity.", "mechanism": "GGT elevation is associated with hepatic fat accumulation.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "O-glycosylation modulates CK18-M65 serum levels.", "mechanism": "CK18-M65 is used to predict response to therapy and degree of liver injury in MASLD.", "protein": "Cytokeratin 18-M65", "relationship_type": "biomarker", "source_pmcid": "PMC12145825" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Lactylation (not classical glycosylation) at lysine residues modulates chromatin accessibility.", "mechanism": "H3K18 lactylation promotes transcription of oncogenes and chemokines, driving proliferation, angiogenesis, and immune modulation.", "protein": "Histone H3 (H3K18)", "protein_enriched": { "function": "Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central r", "gene_name": "H3C1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P68431" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12146230" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Lactylation at lysine 12 alters histone function; not classical glycosylation.", "mechanism": "H4K12 lactylation regulates osteogenic gene expression, affecting bone formation and differentiation.", "protein": "Histone H4 (H4K12)", "relationship_type": "causal", "source_pmcid": "PMC12146230" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Lactylation at K62; not classical glycosylation.", "mechanism": "PKM2-K62 lactylation modulates macrophage polarization and inflammatory response.", "protein": "Pyruvate Kinase M2 (PKM2)", "relationship_type": "causal", "source_pmcid": "PMC12146230" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Lactylation at K677; not classical glycosylation.", "mechanism": "Tau-K677 lactylation regulates ferroptosis and neuronal damage, impacting AD progression.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12146230" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "Lactylation at K33; not classical glycosylation.", "mechanism": "NEDD4-K33 lactylation regulates Caspase-11-mediated pyroptosis, exacerbating liver damage.", "protein": "NEDD4", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including ", "gene_name": "NEDD4L", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q96PU5" }, "relationship_type": "causal", "source_pmcid": "PMC12146230" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Lactylation at K91; not classical glycosylation.", "mechanism": "TFEB-K91 lactylation inhibits ubiquitination, stabilizing TFEB and promoting autophagy in cancer cells.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12146230" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Lactylation at K172; DCBLD1 is a membrane glycoprotein, but lactylation is the key modification.", "mechanism": "DCBLD1-K172 lactylation activates PPP pathway, driving proliferation and metastasis.", "protein": "DCBLD1", "protein_enriched": { "function": "Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone ", "gene_name": "PWWP2A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96N64" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12146230" }, { "confidence": "medium", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Lactylation at K245; not classical glycosylation.", "mechanism": "NLRP3-K245 lactylation increases protein stability, promoting inflammasome activation and tissue injury.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12146230" }, { "confidence": "medium", "disease": "Retinal neovascular disease", "glycan_involvement": "Lactylation at K183; not classical glycosylation.", "mechanism": "YY1-K183 lactylation upregulates FGF2, promoting pathological angiogenesis.", "protein": "YY1", "relationship_type": "causal", "source_pmcid": "PMC12146230" }, { "confidence": "medium", "disease": "Cancer (chemoresistance)", "glycan_involvement": "Lactylation at K673; not classical glycosylation.", "mechanism": "MRE11-K673 lactylation enhances DNA repair, leading to resistance to cisplatin and PARP inhibitors.", "protein": "MRE11", "protein_enriched": { "function": "Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:11741547, PubMed:14657032, P", "gene_name": "MRE11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49959" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12146230" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N-glycosylation supports secretion and stability, facilitating interaction with macrophage mannose receptor (CD206).", "mechanism": "Promotes cancer stem cell self-renewal via NOTCH pathway, drives M2 macrophage polarization, induces immunosuppression and temozolomide resistance.", "protein": "SERPINA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12146250" }, { "confidence": "high", "disease": "Breast Cancer (BRCA)", "glycan_involvement": "N-glycosylation affects secretion and immune recognition; post-translational modifications regulate protein level.", "mechanism": "Low protein (despite high mRNA) in ER+ subtype linked to better prognosis; high in TNBC promotes M2 macrophage recruitment and immune evasion.", "protein": "SERPINA1", "relationship_type": "biomarker", "source_pmcid": "PMC12146250" }, { "confidence": "high", "disease": "Clear Cell Renal Cell Carcinoma (ccRCC)", "glycan_involvement": "N-glycosylation may modulate interaction with macrophage receptors.", "mechanism": "Upregulated in EMT+ cells, promotes ECM degradation, angiogenesis via M2 macrophage interaction (CD163), associated with poor prognosis.", "protein": "SERPINA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Pancreatic Ductal Adenocarcinoma (PAAD)", "glycan_involvement": "N-glycosylation required for secretion and protease inhibition.", "mechanism": "Elevated by NF-\u03baB signaling, inhibits neutrophil elastase, enhances autophagic recycling, drives gemcitabine resistance.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation loss may affect stability and function.", "mechanism": "Downregulation leads to ECM degradation, impaired autophagy, genomic instability, and increased metastasis.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "high", "disease": "Alpha-1 Antitrypsin Deficiency (AATD)", "glycan_involvement": "Aberrant glycosylation contributes to misfolding and ER retention.", "mechanism": "Mutations (e.g., Z allele) cause misfolding, ER retention, leading to cirrhosis and emphysema.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Colorectal Adenocarcinoma (COAD)", "glycan_involvement": "N-glycosylation status may affect serum detectability.", "mechanism": "Low protein expression associated with increased invasion, poor differentiation, and complications.", "protein": "SERPINA1", "relationship_type": "biomarker", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Skin Cutaneous Melanoma (SKCM)", "glycan_involvement": "Mutations may alter glycosylation, affecting immune recognition.", "mechanism": "Missense mutations disrupt protein interactions, promote progression and immune escape.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Uterine Corpus Endometrial Carcinoma (UCEC)", "glycan_involvement": "Mutations may impact glycosylation and function.", "mechanism": "High mutation rate (missense) alters ECM regulation, affecting invasion and metastasis.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Amplification may increase glycosylated protein, enhancing tumor-promoting effects.", "mechanism": "Gene amplification increases protein expression, promoting proliferation, invasion, and metastasis.", "protein": "SERPINA1", "relationship_type": "causal", "source_pmcid": "PMC12146250" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "O-glycosylation critical for lubricating function.", "mechanism": "Essential for joint lubrication; loss leads to cartilage degeneration.", "protein": "PRG4 (lubricin)", "relationship_type": "protective", "source_pmcid": "PMC12146411" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Chondroitin sulfate and keratan sulfate glycosaminoglycan chains lost in OA.", "mechanism": "Proteolytic fragments increase in OA, reflecting ECM breakdown.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation modulates ECM interactions.", "mechanism": "Proteolytic fragments accumulate in OA cartilage.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation affects secretion and ECM assembly.", "mechanism": "Elevated in OA cartilage and synovial fluid.", "protein": "COMP", "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Upregulated in OA cartilage and synovial fluid.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Increased in OA cartilage explant secretome.", "protein": "YKL-39 (CHI3L2)", "protein_enriched": { "function": "Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to", "gene_name": "CHIA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZP6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N- and O-glycosylation modulate hyaluronan binding.", "mechanism": "Mediates chondrocyte-ECM interactions; altered in OA.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12146411" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation affects ECM binding.", "mechanism": "Altered levels in OA cartilage.", "protein": "SPARC", "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Obesity-associated Osteoarthritis", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Upregulated in inflammatory fibroblast endotype in obese OA synovium.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12146411" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Directly synthesizes glycosaminoglycan chains.", "mechanism": "Hyaluronan is a major synovial glycosaminoglycan; altered synthesis in RA.", "protein": "Hyaluronic acid synthase (via hyaluronan)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12146411" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Mutations disrupt N-glycosylation and trafficking, causing ER retention or reduced surface expression.", "mechanism": "Pathogenic mutations (G443D, G443V) in hGAT-1 abolish GABA transport, leading to seizures.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "medium", "disease": "Autism spectrum disorder", "glycan_involvement": "Defective glycosylation affects protein folding and trafficking.", "mechanism": "Loss-of-function mutations impair GABAergic signaling, contributing to ASD.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "medium", "disease": "Intellectual disability", "glycan_involvement": "Glycosylation defects reduce mature protein at plasma membrane.", "mechanism": "Impaired GABA uptake due to misfolded hGAT-1 leads to neurodevelopmental deficits.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "medium", "disease": "Developmental delay", "glycan_involvement": "Altered glycosylation impairs trafficking and function.", "mechanism": "GAT-1 mutations disrupt synaptic GABA clearance, affecting brain development.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Chaperone treatment increases mature glycosylated protein at cell surface.", "mechanism": "Pharmacochaperones (4-PBA, glycerol) restore folding, trafficking, and function of mutant hGAT-1.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12146831" }, { "confidence": "high", "disease": "Creatine transporter deficiency (CTD)", "glycan_involvement": "Mutations affect glycosylation and membrane trafficking.", "mechanism": "G466R and G132V mutations cause folding defects, leading to CTD with epilepsy and intellectual disability.", "protein": "Creatine transporter 1 (CRT-1)", "protein_enriched": { "function": "Creatine:sodium symporter which mediates the uptake of creatine (PubMed:17465020, PubMed:22644605, PubMed:25861866, PubMed:7945388, PubMed:7953292, PubMed:9882430). Plays an important role in supplyin", "gene_name": "SLC6A8", "glycan_count": 3, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G26436YP", "G41891LD", "G49108TO" ], "uniprot_id": "P48029" }, "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "medium", "disease": "Hyperekplexia", "glycan_involvement": "Defective glycosylation leads to ER retention.", "mechanism": "Trafficking-deficient GlyT2 variants cause hyperekplexia due to impaired glycine transport.", "protein": "Glycine transporter 2 (GlyT2)", "protein_enriched": { "function": "Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of", "gene_name": "AP4E1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UPM8" }, "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Glycosylation status can indicate trafficking defects.", "mechanism": "GAT-1 mutations serve as genetic biomarkers for epilepsy syndromes.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12146831" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Calnexin assists folding and glycosylation in ER.", "mechanism": "Calnexin overexpression rescues trafficking of WT hGAT-1 co-expressed with mutant (G443V).", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12146831" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "G443V: only core-glycosylated (ER); G443D: some mature glycosylation (plasma membrane).", "mechanism": "G443V mutation causes complete ER retention and loss of function; G443D partially traffics but is non-functional.", "protein": "Human GABA transporter 1 (hGAT-1)", "relationship_type": "causal", "source_pmcid": "PMC12146831" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "\u03b22-glycoprotein I is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are diagnostic for APS and mediate autoimmune injury.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Bad obstetric history (BOH)", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I may modulate immune recognition.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies contribute to adverse pregnancy outcomes via complement activation and trophoblast injury.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Some cardiolipin-binding proteins are glycosylated, influencing antibody binding.", "mechanism": "Anti-cardiolipin antibodies are diagnostic for APS.", "protein": "Cardiolipin-binding proteins (via anti-cardiolipin antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Target proteins may be glycosylated, affecting antibody interaction.", "mechanism": "Lupus anticoagulant is a functional antibody test for APS.", "protein": "Lupus anticoagulant target proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Thromboembolic events", "glycan_involvement": "Glycosylation may affect protein function and immune complex formation.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies promote thrombosis via endothelial and complement activation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Recurrent miscarriage", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Antibody-mediated injury to trophoblasts leads to pregnancy loss.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Stillbirth", "glycan_involvement": "Glycosylation may influence pathogenicity.", "mechanism": "Placental injury from antibody binding causes fetal demise.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Preterm delivery", "glycan_involvement": "Glycosylation may affect immune complex formation.", "mechanism": "Placental dysfunction from antibody-mediated injury leads to preterm birth.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "medium", "disease": "Intrauterine growth restriction", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Impaired placental function due to antibody binding.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "low", "disease": "Congenital anomalies", "glycan_involvement": "Glycosylation may influence protein-antibody interactions.", "mechanism": "Immune-mediated placental dysfunction may contribute to anomalies.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12168575" }, { "confidence": "high", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "CD36 glycosylation modulates structure/function, critical for ligand (oxLDL) recognition and cholesterol metabolism.", "mechanism": "Increased CD36 expression and palmitoylation in podocytes enhances fatty acid uptake, leading to lipid accumulation and DKD progression.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12210380" }, { "confidence": "high", "disease": "Podocyte injury", "glycan_involvement": "Glycosylation affects CD36's ligand binding and trafficking.", "mechanism": "Membrane-anchored, palmitoylated CD36 increases lipid uptake, causing podocyte lipotoxicity and apoptosis.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12210380" }, { "confidence": "high", "disease": "Lipotoxicity", "glycan_involvement": "Glycosylation is important for CD36's function in lipid uptake.", "mechanism": "Palmitoylated CD36 on the plasma membrane increases fatty acid uptake, driving lipotoxicity in podocytes.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12210380" }, { "confidence": "high", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "No direct glycosylation involvement for APT1 reported.", "mechanism": "APT1 depalmitoylates CD36, promoting its lysosomal degradation and reducing membrane CD36, thus alleviating lipid accumulation and DKD.", "protein": "APT1", "relationship_type": "protective", "source_pmcid": "PMC12210380" }, { "confidence": "high", "disease": "Podocyte injury", "glycan_involvement": "No direct glycosylation involvement for APT1 reported.", "mechanism": "APT1 overexpression reduces palmitoylated CD36, decreasing lipid uptake and podocyte apoptosis.", "protein": "APT1", "relationship_type": "protective", "source_pmcid": "PMC12210380" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "Glycosylation is critical for CD36's pathological role.", "mechanism": "Targeting CD36 palmitoylation or glycosylation may reduce lipid accumulation and DKD progression.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12210380" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "No direct glycosylation involvement for APT1 reported.", "mechanism": "Enhancing APT1 activity or expression could reduce CD36-mediated lipotoxicity in DKD.", "protein": "APT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12210380" }, { "confidence": "medium", "disease": "Lipotoxicity", "glycan_involvement": "Glycosylation status may affect biomarker utility.", "mechanism": "Increased membrane CD36 and its palmitoylation status indicate podocyte lipotoxic stress.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210380" }, { "confidence": "medium", "disease": "Podocyte injury", "glycan_involvement": "Glycosylation may modulate detection/trafficking.", "mechanism": "Elevated CD36 expression and palmitoylation correlate with podocyte injury severity.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210380" }, { "confidence": "medium", "disease": "Diabetic kidney disease (DKD)", "glycan_involvement": "Glycosylation is important for CD36's stability and function.", "mechanism": "CD36 upregulation in glomeruli is associated with DKD progression.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210380" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CtsD is a glycoprotein; glycosylation is essential for its lysosomal targeting and activity.", "mechanism": "Reduced maturation and activity of CtsD impairs lysosomal degradation and autophagic flux, leading to lipid accumulation and MASLD progression.", "protein": "Cathepsin D (CtsD)", "relationship_type": "causal", "source_pmcid": "PMC12210384" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CtsB glycosylation is required for lysosomal localization and function.", "mechanism": "Decreased CtsB activity impairs lysosomal function and autophagy, promoting hepatic lipid accumulation and MASLD.", "protein": "Cathepsin B (CtsB)", "relationship_type": "causal", "source_pmcid": "PMC12210384" }, { "confidence": "medium", "disease": "Lysosomal storage disorder", "glycan_involvement": "CtsE is glycosylated for lysosomal targeting.", "mechanism": "CtsE deficiency or altered expression is linked to lysosomal storage disorder phenotypes in macrophages and may contribute to hepatic dysfunction.", "protein": "Cathepsin E (CtsE)", "protein_enriched": { "function": "May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte deplet", "gene_name": "CTSE", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P14091" }, "relationship_type": "causal", "source_pmcid": "PMC12210384" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "LAMP1 is heavily glycosylated; glycosylation maintains lysosomal membrane integrity.", "mechanism": "Upregulation of LAMP1 marks lysosomal expansion and dysfunction in MASLD.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC12210384" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "LAMP2 glycosylation is critical for lysosomal stability.", "mechanism": "Increased LAMP2 expression indicates lysosomal biogenesis and dysfunction in MASLD.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", 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dysfunction in MASLD.", "protein": "LGP85 (LIMP-2)", "relationship_type": "causal", "source_pmcid": "PMC12210384" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "CD36 glycosylation modulates its cell surface expression and function.", "mechanism": "Upregulation of CD36 enhances fatty acid uptake, contributing to hepatic lipid accumulation in MASLD.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. 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glycosylation affects its clearance and detection.", "mechanism": "Elevated D-dimer indicates fibrin degradation and is used to diagnose/exclude PE.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect D-dimer stability and immunoassay detection.", "mechanism": "Elevated D-dimer levels are associated with COVID-19 severity and thrombotic complications.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "high", "disease": "Deep vein thrombosis", "glycan_involvement": "Glycosylation influences D-dimer's half-life and immunoreactivity.", "mechanism": "Elevated D-dimer is indicative of active clot formation and breakdown in DVT.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion/aggregation; glycosylation modulates function.", "mechanism": "COVID-19 can cause platelet activation and consumption, leading to thrombocytopenia.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Altered glycosylation may affect platelet clearance and immune recognition.", "mechanism": "Low platelet count is common in severe COVID-19 and predicts poor outcome.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "Microvascular thrombosis", "glycan_involvement": "Glycosylation of platelet glycoproteins regulates adhesion and aggregation.", "mechanism": "Platelet activation contributes to microvascular clot formation in COVID-19.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "Microvascular thrombosis", "glycan_involvement": "Glycosylation affects D-dimer's detection in plasma.", "mechanism": "Elevated D-dimer reflects ongoing microvascular clot formation and breakdown.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "low", "disease": "Renal failure", "glycan_involvement": "Glycosylation may influence renal clearance of D-dimer.", "mechanism": "High D-dimer may indicate renal microthrombosis in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation modulates platelet glycoprotein function in clot formation.", "mechanism": "Platelet activation and aggregation contribute to thrombus formation in PE.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12212239" }, { "confidence": "medium", "disease": "Deep vein thrombosis", "glycan_involvement": "Glycosylation affects platelet interaction with endothelium and clot stability.", "mechanism": "Platelet glycoproteins mediate aggregation in DVT pathogenesis.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12212239" }, { "confidence": "high", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "Hemagglutinin glycosylation modulates host cell entry and immune evasion.", "mechanism": "Viral infection triggers immune-mediated muscle inflammation.", "protein": "Influenza B virus hemagglutinin", "protein_enriched": { "function": "Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-d", "gene_name": "HA", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03452" }, "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "medium", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "Glycosylation affects receptor binding and host tropism.", "mechanism": "Viral infection leads to muscle inflammation, especially in children.", "protein": "Influenza A virus hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "F protein glycosylation influences fusion and immune recognition.", "mechanism": "RSV infection occasionally associated with BACM.", "protein": "RSV F protein", "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "Spike glycosylation shields epitopes and modulates host interaction.", "mechanism": "Rare cases of BACM following SARS-CoV-2 infection.", "protein": "SARS-CoV-2 spike protein", "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "gB glycosylation affects viral entry and immune evasion.", "mechanism": "CMV infection sporadically linked to BACM.", "protein": "Cytomegalovirus gB", "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "VP1 glycosylation may influence host cell binding.", "mechanism": "Coxsackievirus can trigger muscle inflammation.", "protein": "Coxsackievirus VP1", "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "Fiber protein glycosylation mediates host cell attachment.", "mechanism": "Adenovirus infection occasionally associated with BACM.", "protein": "Adenovirus fiber protein", "protein_enriched": { "function": "Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chapero", "gene_name": "L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04133" }, "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "P1 adhesin glycosylation aids in host cell adherence.", "mechanism": "Mycoplasma infection can rarely trigger BACM.", "protein": "Mycoplasma pneumoniae P1 adhesin", "protein_enriched": { "function": "", "gene_name": "osh3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O13944" }, "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "M protein glycosylation modulates immune evasion.", "mechanism": "Streptococcal infection rarely linked to BACM.", "protein": "Streptococcus pyogenes M protein", "protein_enriched": { "function": "Positive regulator of sigma-B activity. Non-phosphorylated RsbV binds to RsbW, preventing its association with sigma-B. When phosphorylated, releases RsbW, which is then free to complex with and inact", "gene_name": "rsbV", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0Q7" }, "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "low", "disease": "Benign Acute Childhood Myositis (BACM)", "glycan_involvement": "OmpA glycosylation may affect host-pathogen interaction.", "mechanism": "Salmonella infection sporadically associated with BACM.", "protein": "Salmonella OmpA", "protein_enriched": { "function": "Inhibits the supercoiling activity of DNA gyrase. Acts by inhibiting DNA gyrase at an early step, prior to (or at the step of) binding of DNA by the gyrase. It protects cells against toxins that targe", "gene_name": "sbmC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A213" }, "relationship_type": "causal", "source_pmcid": "PMC12212264" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "FAP functional activation depends on glycosylation and dimerization.", "mechanism": "FAP is overexpressed on activated RA-FLS, mediating joint inflammation, tissue destruction, and serving as a target for imaging and therapy.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12213267" }, { "confidence": "medium", "disease": "Osteoarthritis (OA)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP is expressed in OA synovium, but at lower levels than RA; FAPI imaging detects OA-affected joints.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213267" }, { "confidence": "medium", "disease": "Ankylosing Spondylitis (AS)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAPI imaging shows increased uptake in sacroiliac and costovertebral joints, indicating FAP involvement in inflammation.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213267" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP is overexpressed in fibrotic lung tissue; FAPI PET/CT detects and monitors fibrotic activity.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12213267" }, { "confidence": "high", "disease": "Cardiac Fibrosis", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP is upregulated in cardiac fibroblasts post-injury; FAPI imaging detects myocardial fibrosis.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12213267" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP is highly expressed in tumor-associated fibroblasts, promoting tumor growth, invasion, and immune evasion; target for imaging and therapy.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12213267" }, { "confidence": "medium", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP is upregulated in myofibroblasts in infarcted myocardium, indicating tissue remodeling.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213267" }, { "confidence": "medium", "disease": "Systemic Sclerosis-associated ILD (SSc-ILD)", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAPI uptake correlates with disease activity and progression in SSc-ILD.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213267" }, { "confidence": "low", "disease": "Rheumatoid Nodules", "glycan_involvement": "Glycosylation required for FAP function.", "mechanism": "FAP may help differentiate rheumatoid nodules from malignancy via imaging, though further validation is needed.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker (potential)", "source_pmcid": "PMC12213267" }, { "confidence": "low", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "DPPIV is a glycoprotein; glycosylation affects its function.", "mechanism": "DPPIV shares homology and dimerizes with FAP, potentially modulating FAP activity in RA.", "protein": "Dipeptidyl Peptidase IV (DPPIV)", "relationship_type": "associated", "source_pmcid": "PMC12213267" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP expression increases TNF-\u03b1, promoting liver inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213335" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "High CRP expression correlates with increased TNF-\u03b1 and progression to steatohepatitis.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "causal", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "Glycosylation may regulate SLC7A11 membrane localization and activity.", "mechanism": "SLC7A11 inhibits ferroptosis in hepatocytes, reducing iron-induced damage.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation could affect SLC7A11 function in antioxidant defense.", "mechanism": "Higher SLC7A11 expression reduces TNF-\u03b1 and liver inflammation.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Potential glycosylation may influence CRY1 stability.", "mechanism": "CRY1 inhibits proinflammatory cytokine production, lowering liver inflammation.", "protein": "CRY1", "relationship_type": "protective", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "GALK1 is a glycoprotein; glycosylation may affect its enzymatic activity.", "mechanism": "GALK1 expression is associated with fat deposition in liver.", "protein": "GALK1", "relationship_type": "biomarker", "source_pmcid": "PMC12213335" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "TNF-\u03b1 is glycosylated, which can modulate its receptor interactions.", "mechanism": "Elevated TNF-\u03b1 drives progression from steatosis to steatohepatitis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation of CRP influences its inflammatory signaling.", "mechanism": "CRP-induced TNF-\u03b1 promotes fibrotic changes in liver.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "causal", "source_pmcid": "PMC12213335" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may affect SLC7A11's antioxidant function.", "mechanism": "SLC7A11 expression reduces lipid peroxidation and steatosis.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12213335" }, { "confidence": "low", "disease": "Steatohepatitis", "glycan_involvement": "Possible glycosylation may stabilize CRY1.", "mechanism": "CRY1 suppresses inflammatory cytokines, mitigating steatohepatitis.", "protein": "CRY1", "relationship_type": "protective", "source_pmcid": "PMC12213335" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "LPS O-antigen is a glycan structure; its biosynthesis is upregulated in CRC-associated microbiota.", "mechanism": "Promotes inflammation via TLR4-NF-\u03baB signaling, facilitating tumor progression and immune evasion.", "protein": "Lipopolysaccharide (LPS) O-antigen", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CEA is a heavily glycosylated human glycoprotein; glycosylation affects its stability and detection.", "mechanism": "Serum CEA levels correlate with CRC stage and tumor burden.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213350" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "LPS glycan structures interact with host immune receptors.", "mechanism": "Induces DNA damage, EMT, and inflammation in tumor microenvironment.", "protein": "Fusobacterium nucleatum LPS", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Surface glycoproteins may mediate host-microbe interactions.", "mechanism": "Promotes tumorigenesis via epigenetic reprogramming and Th17 immune response.", "protein": "Parvimonas micra surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Bacterial glycoproteins/LPS may trigger host immune responses.", "mechanism": "Enriched in CRC mucosal samples; associated with immune modulation and inflammation.", "protein": "Prevotella 9 LPS/glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12213350" }, { "confidence": "low", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Bacterial glycoproteins/LPS may influence host immunity.", "mechanism": "Unexpectedly abundant in CRC; possible role in immune modulation.", "protein": "Holdemanella LPS/glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Central to bacterial glycan assembly in CRC-associated microbiota.", "mechanism": "Precursor for LPS O-antigen biosynthesis, supporting pro-inflammatory environment.", "protein": "UDP-N-acetylglucosamine-derived O-antigen", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycan precursor for LPS in CRC-associated bacteria.", "mechanism": "Essential for LPS core biosynthesis, contributing to immune activation.", "protein": "GDP-D-glycero-\u03b1-D-manno-heptose", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycan precursor for LPS in CRC-associated bacteria.", "mechanism": "Required for LPS biosynthesis, promoting inflammation.", "protein": "CMP-3-deoxy-D-manno-octulosonate", "relationship_type": "causal", "source_pmcid": "PMC12213350" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Surface glycoproteins may mediate host-microbe interactions.", "mechanism": "Enriched in CRC mucosal samples; potential diagnostic marker.", "protein": "Eubacterium ramosum surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12213350" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects fibrinogen's stability and function in coagulation and immune response.", "mechanism": "Fibrinogen is an acute-phase glycoprotein elevated in inflammation and coagulopathy during sepsis; both high and low levels are associated with increased mortality.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Minor glycosylation; not a major determinant of function in this context.", "mechanism": "Low albumin reflects poor nutritional and inflammatory status, correlating with higher mortality in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Coronary heart disease", "glycan_involvement": "N-glycosylation modulates fibrinogen's prothrombotic properties.", "mechanism": "Elevated fibrinogen is linked to increased risk and adverse outcomes in coronary heart disease.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "N-glycosylation influences fibrinogen's clotting activity.", "mechanism": "High fibrinogen levels are associated with increased risk of stroke due to enhanced coagulation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "N-glycosylation may affect clearance and function.", "mechanism": "Elevated FAR predicts adverse outcomes in CKD, reflecting inflammation and coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation may modulate immune interactions.", "mechanism": "High FAR is associated with worse outcomes in COVID-19, reflecting hypercoagulability and inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation can alter fibrinogen's interactions with tumor cells.", "mechanism": "Elevated FAR is linked to poor prognosis in cancer, indicating systemic inflammation and coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Peritonitis-induced sepsis", "glycan_involvement": "N-glycosylation affects fibrinogen's inflammatory role.", "mechanism": "FAR predicts short-term prognosis in surgical sepsis due to peritonitis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation", "glycan_involvement": "N-glycosylation impacts fibrinogen's susceptibility to proteolysis.", "mechanism": "Low fibrinogen may indicate DIC in sepsis, associated with poor outcomes.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213360" }, { "confidence": "medium", "disease": "Multiple organ dysfunction syndrome", "glycan_involvement": "N-glycosylation modulates immune and coagulation functions.", "mechanism": "Altered fibrinogen levels reflect severity and progression to MODS in sepsis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213360" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HDL particles are glycoproteins; altered glycosylation may affect function and disease risk.", "mechanism": "Higher HDL-C levels are associated with lower MASLD risk, likely via reverse cholesterol transport, antioxidant, and anti-inflammatory effects.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12213369" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Non-HDL-C includes glycosylated apolipoproteins; glycan changes may modulate atherogenicity.", "mechanism": "Elevated non-HDL-C predicts increased MASLD risk; reflects atherogenic lipoprotein burden and hepatic lipid overload.", "protein": "non-HDL-C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213369" }, { "confidence": "medium", "disease": "CVD", "glycan_involvement": "HDL glycosylation affects anti-inflammatory properties.", "mechanism": "HDL-C is inversely associated with CVD risk, but very high levels may lose protective effect.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12213369" }, { "confidence": "high", "disease": "CVD", "glycan_involvement": "Glycosylation of apolipoproteins in non-HDL-C influences atherogenicity.", "mechanism": "Non-HDL-C is a strong predictor of CVD due to its inclusion of all atherogenic lipoproteins.", "protein": "non-HDL-C", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12213369" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "LDL is a glycoprotein; glycan modifications may affect hepatic uptake.", "mechanism": "Elevated LDL-C contributes to hepatic lipid accumulation and MASLD risk.", "protein": "LDL-C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213369" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "VLDL glycosylation may influence hepatic lipid delivery.", "mechanism": "Elevated VLDL-C promotes hepatic triglyceride accumulation, increasing MASLD risk.", "protein": "VLDL-C", "relationship_type": "causal", "source_pmcid": "PMC12213369" }, { "confidence": "low", "disease": "NASH", "glycan_involvement": "HDL glycosylation may modulate anti-inflammatory effects in NASH.", "mechanism": "Estrogen deficiency (which affects HDL-C metabolism) exacerbates NASH in animal models.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12213369" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Sex differences in glycosylation may contribute.", "mechanism": "Non-HDL-C is more predictive of MASLD risk in men than women.", "protein": "non-HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12213369" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Altered HDL glycosylation may impair function.", "mechanism": "Low HDL-C is a diagnostic criterion for MASLD.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12213369" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Reflects combined glycoprotein changes in lipoprotein fractions.", "mechanism": "NHHR is a superior predictor of MASLD risk compared to individual lipid parameters.", "protein": "non-HDL-C/HDL-C ratio (NHHR)", "relationship_type": "biomarker", "source_pmcid": "PMC12213369" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "Insulin is a glycoprotein; glycosylation is required for its secretion and stability.", "mechanism": "\u03b1-amanitin exposure may stimulate pancreatic \u03b2-cells to secrete excess insulin, leading to hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "medium", "disease": "\u03b1-amanitin toxicosis", "glycan_involvement": "Glycosylation affects insulin's half-life and receptor binding.", "mechanism": "Elevated serum insulin may serve as a biomarker for \u03b1-amanitin-induced hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213408" }, { "confidence": "high", "disease": "Fulminant hepatic necrosis", "glycan_involvement": "No direct glycan involvement.", "mechanism": "\u03b1-amanitin inhibits RNA polymerase II, blocking mRNA synthesis and leading to hepatocyte death.", "protein": "RNA polymerase II", "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "high", "disease": "Renal tubular necrosis", "glycan_involvement": "No direct glycan involvement.", "mechanism": "\u03b1-amanitin inhibits RNA polymerase II in renal tubular cells, causing cell death.", "protein": "RNA polymerase II", "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "medium", "disease": "Laminar neuronal necrosis", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Inhibition of RNA polymerase II in neurons may contribute to neuronal death.", "protein": "RNA polymerase II", "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "medium", "disease": "Laminar neuronal necrosis", "glycan_involvement": "Insulin glycosylation is essential for function.", "mechanism": "Excess insulin-induced hypoglycemia can cause acute neuronal necrosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "medium", "disease": "Multi-organ failure", "glycan_involvement": "Glycosylation required for insulin activity.", "mechanism": "Hypoglycemia from hyperinsulinemia may contribute to systemic organ dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12213408" }, { "confidence": "low", "disease": "Fulminant hepatic necrosis", "glycan_involvement": "Glycosylation affects insulin clearance by the liver.", "mechanism": "Elevated insulin may indicate hepatic dysfunction in \u03b1-amanitin toxicosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213408" }, { "confidence": "low", "disease": "Renal tubular necrosis", "glycan_involvement": "Glycosylation impacts renal handling of insulin.", "mechanism": "Insulin levels may be altered due to renal clearance impairment.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213408" }, { "confidence": "low", "disease": "\u03b1-amanitin toxicosis", "glycan_involvement": "Glycosylation status could affect therapeutic strategies.", "mechanism": "Managing insulin levels may mitigate hypoglycemia in \u03b1-amanitin poisoning.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12213408" }, { "confidence": "high", "disease": "Acute Hemorrhagic Leukoencephalitis (AHLE)", "glycan_involvement": "FI is a glycoprotein; glycosylation is required for secretion and function.", "mechanism": "FI deficiency leads to uncontrolled complement activation, causing neuroinflammation and demyelination.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "high", "disease": "Atypical Hemolytic Uremic Syndrome (aHUS)", "glycan_involvement": "FI glycosylation affects stability and plasma half-life.", "mechanism": "Pathogenic CFI variants cause FI deficiency, leading to complement-mediated endothelial injury.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Age-related Macular Degeneration", "glycan_involvement": "FI glycosylation may affect tissue distribution.", "mechanism": "Incomplete FI deficiency increases risk via chronic complement activation in retinal tissue.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "high", "disease": "Recurrent Bacterial Infections", "glycan_involvement": "Glycosylation required for FI secretion and activity.", "mechanism": "FI deficiency impairs complement regulation, increasing susceptibility to infections.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Acute Disseminated Encephalomyelitis (ADEM)", "glycan_involvement": "FI glycosylation required for function.", "mechanism": "FI deficiency reported in cases with ADEM-like neuroinflammation.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "CNS Vasculitis", "glycan_involvement": "Glycosylation required for FI activity.", "mechanism": "FI deficiency associated with CNS vasculitis via complement overactivation.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Longitudinal Extensive Transverse Myelitis", "glycan_involvement": "FI glycosylation required for function.", "mechanism": "FI deficiency linked to demyelinating spinal cord disease.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Aseptic Encephalomeningitis", "glycan_involvement": "FI glycosylation required for function.", "mechanism": "FI deficiency reported in cases of aseptic neuroinflammation.", "protein": "Complement Factor I (FI)", "relationship_type": "causal", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Acute Hemorrhagic Leukoencephalitis (AHLE)", "glycan_involvement": "FB is a glycoprotein; glycosylation required for function.", "mechanism": "Low FB levels indicate complement consumption in FI deficiency-associated AHLE.", "protein": "Complement Factor B (FB)", "relationship_type": "biomarker", "source_pmcid": "PMC12213424" }, { "confidence": "medium", "disease": "Acute Hemorrhagic Leukoencephalitis (AHLE)", "glycan_involvement": "MOG is a CNS glycoprotein; glycosylation affects antigenicity.", "mechanism": "MOG antibody testing used to exclude MOG-associated demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12213424" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies target BP180, leading to dermal-epidermal separation and blister formation.", "protein": "BP180 (Collagen XVII)", "relationship_type": "causal", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Autoantibodies against BP230 contribute to disease pathology and are linked to neurological comorbidities.", "protein": "BP230 (Dystonin)", "relationship_type": "causal", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation of HLA affects peptide binding and T cell activation.", "mechanism": "Susceptibility allele promotes presentation of BP180/BP230 epitopes, increasing risk.", "protein": "HLA-DQB1*03:01", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12213434" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "Associated with increased BP risk in Han Chinese population.", "protein": "HLA-DRB1*10:01", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Type 2 diabetes (DPP4i-induced BP)", "glycan_involvement": "Glycosylation impacts HLA function.", "mechanism": "Predicts risk of BP in patients treated with DPP4 inhibitors.", "protein": "HLA-DQB1*03:01", "relationship_type": "biomarker", "source_pmcid": "PMC12213434" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation regulates receptor function and antibody binding.", "mechanism": "Low copy number increases susceptibility by enhancing neutrophil activation via IgG autoantibodies.", "protein": "FcgRIIIb (CD16b)", "relationship_type": "causal", "source_pmcid": "PMC12213434" }, { "confidence": "low", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation essential for membrane localization and function.", "mechanism": "Genetic variants may affect drug transport and immune response.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "risk factor", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation affects cytokine stability and receptor binding.", "mechanism": "Promotes eosinophil recruitment, B cell maturation, and IgE production; associated with pruritus.", "protein": "IL-13", "protein_enriched": { "function": "Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immun", "gene_name": "IL15", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P40933" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213434" }, { "confidence": "medium", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "Elevated levels induce neutrophil recruitment and NET formation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation required for secretion and enzymatic activity.", "mechanism": "Degrades BP180 and extracellular matrix, leading to blister formation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12213434" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLP-1 is O-glycosylated, affecting its stability and receptor interaction.", "mechanism": "GLP-1 secretion is reduced by altered gut flora, impairing appetite suppression and glucose regulation.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "FGF21 is N-glycosylated, influencing secretion and receptor binding.", "mechanism": "Gut flora metabolites (pantothenate) activate the GLP-1/FGF21 axis, regulating glucose preference and energy balance.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "PYY is O-glycosylated, modulating its half-life.", "mechanism": "Reduced SCFA production by gut flora decreases PYY secretion, impairing appetite inhibition.", "protein": "PYY", "relationship_type": "protective", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Leptin is N-glycosylated, affecting receptor binding and signaling.", "mechanism": "LPS from dysbiotic flora activates TLR4, inducing hypothalamic inflammation and interfering with leptin signaling.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Insulin is not glycosylated, but its receptor is N-glycosylated, affecting signaling.", "mechanism": "Insulin resistance in the brain impairs appetite regulation and is exacerbated by gut flora dysbiosis.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12213503" }, { "confidence": "high", "disease": "Chronic low-grade inflammation", "glycan_involvement": "TLR4 is N-glycosylated, required for proper folding and function.", "mechanism": "LPS from gut flora activates TLR4, triggering systemic and neuroinflammation.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation modulates GLP-1 activity.", "mechanism": "SCFA-induced GLP-1 secretion suppresses appetite; reduced SCFA from flora impairs this effect.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation of leptin receptor modulates signaling.", "mechanism": "Inflammation impairs leptin signaling in the hypothalamus, promoting overeating.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12213503" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "O-glycosylation affects PYY stability.", "mechanism": "Reduced PYY due to flora dysbiosis impairs appetite and glucose regulation.", "protein": "PYY", "relationship_type": "protective", "source_pmcid": "PMC12213503" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation essential for TLR4 function.", "mechanism": "TLR4 activation by LPS from gut flora induces neuroinflammation, affecting appetite regulation.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12213503" }, { "confidence": "high", "disease": "Renal neuroendocrine tumor (NET)", "glycan_involvement": "Glycosylation affects CgA secretion and stability, impacting its detectability as a biomarker.", "mechanism": "CgA is a secreted glycoprotein used as a serum marker for neuroendocrine tumors; its expression supports diagnosis.", "protein": "Chromogranin A (CgA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "high", "disease": "Renal neuroendocrine tumor (NET)", "glycan_involvement": "CD56 is a heavily glycosylated membrane protein; glycosylation modulates cell adhesion and tumor cell interactions.", "mechanism": "CD56 is highly expressed in renal NETs, supporting neuroendocrine differentiation.", "protein": "Neural Cell Adhesion Molecule (CD56)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "high", "disease": "Renal neuroendocrine tumor (NET)", "glycan_involvement": "Glycosylation of Syn influences its membrane localization and function in neuroendocrine cells.", "mechanism": "Synaptophysin is strongly expressed in renal NETs, confirming neuroendocrine origin.", "protein": "Synaptophysin (Syn)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "medium", "disease": "Carcinoid syndrome", "glycan_involvement": "Altered glycosylation may affect CgA release and serum levels.", "mechanism": "Elevated CgA levels are associated with bioactive substance secretion in carcinoid syndrome.", "protein": "Chromogranin A (CgA)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "medium", "disease": "Metastatic renal NET", "glycan_involvement": "Glycosylation state may influence metastatic potential via cell adhesion properties.", "mechanism": "CD56 expression persists in metastatic NETs, aiding in identification of metastatic lesions.", "protein": "Neural Cell Adhesion Molecule (CD56)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "medium", "disease": "Metastatic renal NET", "glycan_involvement": "Glycosylation may affect protein stability in metastatic cells.", "mechanism": "Synaptophysin remains a marker in metastatic NETs, confirming neuroendocrine lineage.", "protein": "Synaptophysin (Syn)", "relationship_type": "biomarker", "source_pmcid": "PMC12213506" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSMA is a glycoprotein; glycosylation may affect antibody recognition and stability.", "mechanism": "PSMA is overexpressed on prostate cancer cells; targeted by CAR T cells, monoclonal antibodies, and antibody-drug conjugates for therapy.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSCA is a GPI-anchored glycoprotein; glycosylation may influence cell surface localization.", "mechanism": "PSCA is overexpressed in advanced prostate cancer; targeted by CAR T cells to inhibit tumor growth.", "protein": "Prostate stem cell antigen (PSCA)", "protein_enriched": { "function": "May be involved in the regulation of cell proliferation. Has a cell-proliferation inhibition activity in vitro", "gene_name": "PSCA", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43653" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "EpCAM is heavily glycosylated; glycosylation modulates cell adhesion and immune recognition.", "mechanism": "EpCAM is overexpressed in prostate cancer tissues; CAR T cells targeting EpCAM reduce tumor size in models.", "protein": "Epithelial cell adhesion molecule (EpCAM)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "NKG2DLs are glycoproteins; glycosylation affects ligand stability and immune recognition.", "mechanism": "NKG2DLs are upregulated in tumors; CAR T cells targeting NKG2DL control tumor growth in models.", "protein": "Natural killer group 2D ligand (NKG2DL)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "STEAP2 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "STEAP2 is highly expressed in prostate tumors; CAR T cells targeting STEAP2 reduce tumor growth.", "protein": "Six-transmembrane epithelial antigen of prostate-2 (STEAP2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "B7-H3 is glycosylated; glycosylation may modulate immune checkpoint function.", "mechanism": "B7-H3 is expressed on prostate cancer stem cells; CAR T cells targeting B7-H3 inhibit tumor growth.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "N-cadherin is glycosylated; glycosylation affects cell adhesion and metastatic potential.", "mechanism": "N-cadherin expression is linked to metastasis and treatment resistance; anti-N-cadherin antibodies reduce tumor growth and metastasis.", "protein": "N-cadherin (CDH2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "ENO1 is glycosylated; glycosylation may affect secretion and immune targeting.", "mechanism": "Enolase-1 promotes tumor cell migration; anti-ENO1 antibodies inhibit tumor growth and bone metastasis.", "protein": "Enolase-1 (ENO1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PD-L1 is glycosylated; N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 is overexpressed in aggressive prostate cancer; targeted by immune checkpoint inhibitors to restore T cell function.", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "FGL1 is a secreted glycoprotein; glycosylation may affect ligand-receptor interaction.", "mechanism": "FGL1 is a ligand for LAG-3; accumulates in prostate tumors and supports rapid growth; blocking FGL1-LAG3 interaction enhances T cell activity.", "protein": "FGL1", "protein_enriched": { "function": "Immune suppressive molecule that inhibits antigen-specific T-cell activation by acting as a major ligand of LAG3 (PubMed:30580966). Responsible for LAG3 T-cell inhibitory function (PubMed:30580966). B", "gene_name": "FGL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q08830" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213564" }, { "confidence": "high", "disease": "Chronic wounds", "glycan_involvement": "Glycosylation critical for ECM interaction and cell binding.", "mechanism": "Supports cell adhesion and migration, promoting tissue repair.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213565" }, { "confidence": "high", "disease": "Chronic wounds", "glycan_involvement": "Glycosylation modulates cell-matrix interactions.", "mechanism": "Facilitates cell adhesion and basement membrane integrity for wound healing.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213565" }, { "confidence": "high", "disease": "Burn-induced injuries", "glycan_involvement": "Glycosylation affects fibril formation and stability.", "mechanism": "Provides structural support for tissue regeneration.", "protein": "Collagen (Type I, III)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213565" }, { "confidence": "medium", "disease": "Diabetic ulcers", "glycan_involvement": "Glycosylation required for functional activity.", "mechanism": "Enhances cell migration and ECM remodeling in impaired healing.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213565" }, { "confidence": "low", "disease": "Infected wounds", "glycan_involvement": "Glycosylation modulates immune cell interactions.", "mechanism": "Supports antimicrobial barrier and cell recruitment.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213565" }, { "confidence": "low", "disease": "Fibrosis", "glycan_involvement": "Glycosylation regulates ECM assembly.", "mechanism": "Maintains normal ECM architecture, limiting fibrotic remodeling.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12213565" }, { "confidence": "high", "disease": "CIDP", "glycan_involvement": "CNTN1 is a glycoprotein; glycosylation may affect antibody binding and immune recognition.", "mechanism": "Autoantibodies against CNTN1 disrupt paranodal axo-glial junctions, leading to demyelination.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12213591" }, { "confidence": "high", "disease": "Membranous glomerulonephritis (MGN)", "glycan_involvement": "Glycosylation of CNTN1 may influence antigenicity and immune complex formation.", "mechanism": "Anti-CNTN1 antibodies cross-react with podocyte antigens, causing immune complex deposition and glomerular injury.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "causal", "source_pmcid": "PMC12213591" }, { "confidence": "high", "disease": "Autoimmune nodopathy", "glycan_involvement": "Glycosylation state may modulate antibody specificity.", "mechanism": "Presence of anti-CNTN1 antibodies defines a subset of autoimmune nodopathies.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213591" }, { "confidence": "high", "disease": "Autoimmune nodopathy", "glycan_involvement": "NF155 is highly glycosylated; glycan structures may affect immune targeting.", "mechanism": "Anti-NF155 antibodies disrupt paranodal architecture, causing neuropathy.", "protein": "Neurofascin-155 (NF155)", "protein_enriched": { "function": "", "gene_name": "NRCAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92823-2" }, "relationship_type": "causal", "source_pmcid": "PMC12213591" }, { "confidence": "medium", "disease": "Focal segmental glomerulosclerosis (FSGS)", "glycan_involvement": "Glycosylation may influence podocyte antigenicity.", "mechanism": "Anti-NF155 antibodies associated with FSGS in nodopathy patients.", "protein": "Neurofascin-155 (NF155)", "protein_enriched": { "function": "", "gene_name": "NRCAM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92823-2" }, "relationship_type": "causal", "source_pmcid": "PMC12213591" }, { "confidence": "high", "disease": "Membranous glomerulonephritis (MGN)", "glycan_involvement": "PLA2R is a glycoprotein; glycosylation affects immune recognition.", "mechanism": "Anti-PLA2R antibodies are a hallmark of primary MGN.", "protein": "Phospholipase A2 receptor (PLA2R)", "relationship_type": "biomarker", "source_pmcid": "PMC12213591" }, { "confidence": "medium", "disease": "Autoimmune nodopathy", "glycan_involvement": "Caspr1 glycosylation may affect antibody binding.", "mechanism": "Anti-Caspr1 antibodies define a subset of nodopathies.", "protein": "Contactin-associated protein 1 (Caspr1)", "protein_enriched": { "function": "Required for gap junction formation (Probable). Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons. Plays a role in the formation of functional distinct domains criti", "gene_name": "CNTNAP2", "glycan_count": 0, "glycosylation_sites_count": 12, "glytoucan_ids": [], "uniprot_id": "Q9UHC6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213591" }, { "confidence": "low", "disease": "Guillain-Barr\u00e9 syndrome (GBS)", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Rare cases of anti-CNTN1 antibodies in GBS-like presentations.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213591" }, { "confidence": "medium", "disease": "Membranous glomerulonephritis (MGN)", "glycan_involvement": "Glycosylation may affect antibody-mediated pathogenicity.", "mechanism": "Rituximab (B cell depletion) effective in anti-CNTN1 antibody-mediated MGN.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12213591" }, { "confidence": "medium", "disease": "CIDP", "glycan_involvement": "Subclass switching may be influenced by glycan presentation.", "mechanism": "IgG4 subclass anti-CNTN1 antibodies are characteristic of chronic phase; IgG1 in acute phase.", "protein": "Contactin-1 (CNTN1)", "protein_enriched": { "function": "Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between ", "gene_name": "CNTN1", "glycan_count": 21, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G28681TP", "G40574BA", "G80920RR", "G98611JV", "G08918WF", "G48414YA", "G08290VR", "G27058EU", "G37399XV", "G56784JY", "G10019LZ", "G11629QQ", "G45395BF", "G62765YT", "G49108TO", "G02815KT", "G31852PQ", "G82463GQ", "G83460ZZ", "G75983OB" ], "uniprot_id": "Q12860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213591" }, { "confidence": "high", "disease": "Fascioliasis", "glycan_involvement": "Glycosylation of parasite antigens enables immune recognition and serological detection.", "mechanism": "Detected by Western blot/ELISA as specific markers for Fasciola hepatica infection.", "protein": "Fasciola hepatica antigenic glycoproteins (10, 12, 17, 23 kDa)", "relationship_type": "biomarker", "source_pmcid": "PMC12213668" }, { "confidence": "medium", "disease": "Subcapsular hepatic hematoma", "glycan_involvement": "Glycoprotein antigens trigger host immune response and inflammation.", "mechanism": "Parasitic migration and antigen-induced inflammation cause hepatic tissue damage, predisposing to hematoma formation.", "protein": "Fasciola hepatica antigenic glycoproteins (10, 12, 17, 23 kDa)", "relationship_type": "causal", "source_pmcid": "PMC12213668" }, { "confidence": "high", "disease": "Eosinophilia", "glycan_involvement": "Glycosylated antigens are potent inducers of Th2/eosinophilic responses.", "mechanism": "Host immune response to glycoprotein antigens leads to marked eosinophilia.", "protein": "Fasciola hepatica antigenic glycoproteins (10, 12, 17, 23 kDa)", "relationship_type": "causal", "source_pmcid": "PMC12213668" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBsAg is a glycosylated envelope protein; glycosylation affects antigenicity and immune recognition.", "mechanism": "HBsAg is used to diagnose and monitor HBV infection and chronicity.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Chronic liver disease (CLD)", "glycan_involvement": "H. pylori surface glycoconjugates mediate immune evasion and persistence.", "mechanism": "H. pylori co-infection exacerbates liver inflammation and progression of CLD in HBV patients.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC12213833" }, { "confidence": "high", "disease": "Chronic liver disease (CLD)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated ALT indicates liver injury, especially in HBV/H. pylori co-infection.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "high", "disease": "Chronic liver disease (CLD)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect function and detection.", "mechanism": "Elevated AST is associated with liver damage in HBV/H. pylori co-infection.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Chronic liver disease (CLD)", "glycan_involvement": "Serum lipoproteins are glycoproteins; glycosylation affects lipid transport.", "mechanism": "Higher TChol levels observed in HBV/H. pylori co-infected patients, indicating altered lipid metabolism.", "protein": "Total cholesterol (TChol)", "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBeAg is glycosylated; glycosylation modulates immune response.", "mechanism": "HBeAg positivity marks active viral replication and immune tolerance phase.", "protein": "HBV e antigen (HBeAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "H. pylori glycoconjugates may promote inflammation and carcinogenesis.", "mechanism": "H. pylori infection increases risk and prevalence of HCC in HBV patients.", "protein": "Helicobacter pylori antigen", "relationship_type": "causal", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "IgG1 is heavily glycosylated; glycosylation affects effector function.", "mechanism": "Th2 response to H. pylori induces IgG1, reflecting immune modulation in HBV.", "protein": "Immunoglobulin G1 (IgG1)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG1", "glycan_count": 221, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00420UH", "G00432WW", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03382KH", "G03574QJ", "G05642HQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09197ZW", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G11254FL", "G11453BM", "G11745XZ", "G11870QZ", "G12398HZ", "G12580WI", "G14260UH", "G14994KB", "G15038BD", "G15486FH", "G15828HX", "G17336WC", "G19379ID", "G20218ZS", "G20449BJ", "G22140GZ", "G22340YC", "G22674CI", "G22768VO", "G23295TF", "G23432EQ", "G23453IV", "G23719VF", "G23770JR", "G23863VK", "G25079LO", "G25520XG", "G25987BV", "G27919IH", "G28541PG", "G28603RA", "G28663KH", "G28681TP", "G29651HS", "G29880MM", "G30159WR", "G31616YD", "G31852PQ", "G31916IQ", "G31936TA", "G32814EW", "G33244HE", "G33271XM", "G34730YF", "G35029YA", "G36191CD", "G37868ZX", "G39213VZ", "G39446WN", "G39943KJ", "G40834TG", "G41247ZX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G45889JQ", "G46687AB", "G46902YN", "G48390IG", "G48414YA", "G48584BU", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50842MS", "G51287LK", "G52162PS", "G52589SM", "G54600FO", "G55052CN", "G56903ZB", "G57317CE", "G57776ZU", "G57818FI", "G58667NI", "G59451NL", "G59471TH", "G59626AS", "G59937CP", "G60145BJ", "G60923RB", "G61334IA", "G61627IG", "G61855PQ", "G61937QU", "G62765YT", "G62894KT", "G64481DJ", "G64527OM", "G65092SV", "G65184UU", "G66760KM", "G66933CM", "G66937TJ", "G67324HN", "G67381VP", "G68318VE", "G68698AP", "G70101JE", "G71013KY", "G71812IK", "G72291OX", "G72787SB", "G72790NZ", "G72791KH", "G74430RZ", "G75798PH", "G77653XA", "G78059CC", "G79568CQ", "G80475RE", "G80858MF", "G80920RR", "G81295CK", "G82081LV", "G83161QT", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84618NL", "G85740DB", "G85767HW", "G86500WE", "G87051GH", "G88374WZ", "G88421PE", "G88725PI", "G89993FE", "G90659AW", "G90725ZC", "G90734RJ", "G91636VS", "G92050GC", "G92129PT", "G92597CK", "G94854LT", "G95865ZB", "G98719SR", "G99858XP", "G02030ZB", "G03127AL", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G16828VN", "G22310AV", "G23294PN", "G24835MQ", "G26403SG", "G32611KT", "G33609NS", "G33780DA", "G36836GD", "G39188ZX", "G40702WU", "G42358LZ", "G43157UW", "G43694RQ", "G47518TP", "G49108TO", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G60230HH", "G62831KM", "G65219TP", "G66538GV", "G69411IG", "G70418MS", "G72667IM", "G72718TT", "G72735IY", "G72956NR", "G74724QE", "G75983OB", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82119TF", "G82463GQ", "G83355KE", "G84467IZ", "G84820NF", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92570PJ", "G94239KE" ], "uniprot_id": "P01857" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "IgG2 glycosylation modulates immune response.", "mechanism": "Th1 response to H. pylori induces IgG2, indicating immune activation in HBV.", "protein": "Immunoglobulin G2 (IgG2)", "relationship_type": "biomarker", "source_pmcid": "PMC12213833" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "DC-SIGN is a C-type lectin glycoprotein; recognizes pathogen glycans.", "mechanism": "H. pylori inhibits DC-SIGN-mediated signaling, dampening antiviral immunity and promoting HBV persistence.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12213833" }, { "confidence": "high", "disease": "LVO-AIS", "glycan_involvement": "N-glycosylation modulates albumin's stability and function", "mechanism": "Antioxidant, anti-inflammatory, antithrombotic, stabilizes blood-brain barrier", "protein": "Serum Albumin", "relationship_type": "protective", "source_pmcid": "PMC12213872" }, { "confidence": "high", "disease": "Poor Functional Outcome (mRS 3\u20136)", "glycan_involvement": "Glycosylation affects albumin's half-life and antioxidant capacity", "mechanism": "Low albumin predicts poor outcome after EVT", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation regulates lymphocyte trafficking and activation", "mechanism": "Lymphocyte activation exacerbates neuroinflammation via cytokine release", "protein": "Lymphocyte Surface Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "high", "disease": "No-reflow Phenomenon", "glycan_involvement": "Glycosylation of P-selectin critical for ligand binding (PSGL-1)", "mechanism": "Platelet activation and P-selectin expression promote microvascular occlusion", "protein": "Platelet Glycoproteins (P-selectin)", "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates CD40L stability and receptor interaction", "mechanism": "CD40L on platelets interacts with lymphocytes, amplifying inflammation", "protein": "CD40 Ligand (CD40L)", "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "high", "disease": "No-reflow Phenomenon", "glycan_involvement": "Sialylated O-glycans essential for P-selectin binding", "mechanism": "PSGL-1 on lymphocytes binds P-selectin, promoting cell adhesion and microvascular occlusion", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for MHC I surface expression", "mechanism": "Platelet MHC I presents antigen to CD8+ T cells, promoting neuroinflammation", "protein": "MHC Class I", "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects CD86 receptor function", "mechanism": "Platelet CD86 co-stimulates T cell activation, exacerbating neuronal injury", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "causal", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Poor Functional Outcome (mRS 3\u20136)", "glycan_involvement": "Apolipoprotein glycosylation affects lipoprotein metabolism", "mechanism": "Low cholesterol predicts malnutrition and poor outcome", "protein": "Total Cholesterol-associated Lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12213872" }, { "confidence": "medium", "disease": "Hemorrhagic Transformation", "glycan_involvement": "Glycosylation modulates platelet activation and aggregation", "mechanism": "Elevated platelet count associated with poor prognosis and vascular complications", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12213872" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Mucin domain (O-glycosylation) mediates protein-protein interactions and phagocytosis.", "mechanism": "Upregulated in proximal tubules after injury; facilitates clearance of apoptotic cells and moderates inflammation.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12213940" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylated extracellular domain may influence immune signaling and fibrosis.", "mechanism": "Persistent KIM-1 expression drives chronic inflammation and interstitial fibrosis, promoting CKD progression.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213940" }, { "confidence": "high", "disease": "Renal Cell Carcinoma (Clear cell and Papillary RCC)", "glycan_involvement": "Mucin domain glycosylation may facilitate tumor cell interactions.", "mechanism": "Upregulated in clear cell and papillary RCC; may promote phagocytosis of apoptotic debris and tumor progression.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12213940" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation may affect stability and detection in urine.", "mechanism": "Urinary KIM-1 correlates with disease activity, tubulointerstitial inflammation, and predicts renal outcomes.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "medium", "disease": "Tubulointerstitial Nephritis", "glycan_involvement": "Glycosylated domains involved in immune modulation.", "mechanism": "KIM-1 upregulation marks proximal tubular injury and inflammation.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "high", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycosylation may affect circulating levels and biomarker utility.", "mechanism": "Elevated plasma KIM-1 predicts progression to kidney failure.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "medium", "disease": "Thrombotic Microangiopathy", "glycan_involvement": "Glycosylation may influence localization in injured tubules.", "mechanism": "KIM-1 staining identifies acute tubular injury secondary to glomerular ischemia.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "medium", "disease": "Sickle Cell Nephropathy", "glycan_involvement": "Glycosylation may affect detection in tissue.", "mechanism": "KIM-1 expression in proximal tubules indicates acute injury due to sickling events.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "medium", "disease": "Tacrolimus Nephrotoxicity", "glycan_involvement": "Glycosylation may impact stability and detection.", "mechanism": "KIM-1 upregulation in medullary rays marks drug-induced acute tubular injury.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "medium", "disease": "COVID-19 Associated Kidney Injury", "glycan_involvement": "Glycosylation may affect immune interactions and biomarker sensitivity.", "mechanism": "KIM-1 is highly expressed in proximal tubules of COVID-19 patients, indicating acute tubular injury even with normal creatinine.", "protein": "Kidney Injury Molecule-1 (KIM-1)", "protein_enriched": { "function": "Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:19276069, PubMed:20634287, PubMed:31439799). Its function seems to be partially redundant with that of CNOT8 (Pub", "gene_name": "CNOT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UIV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12213940" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Altered glycosylation may affect albumin stability and secretion.", "mechanism": "Reduced albumin secretion indicates impaired hepatocyte function in DILI.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214119" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation affects CYPs localization and activity.", "mechanism": "CYPs metabolize drugs; altered activity leads to toxic metabolite accumulation.", "protein": "Cytochrome P450 enzymes (CYPs)", "relationship_type": "causal", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation may modulate Nrf2 stability and nuclear translocation.", "mechanism": "Nrf2 regulates antioxidant response, reducing oxidative stress in DILI.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect HNF4\u03b1 DNA binding and stability.", "mechanism": "HNF4\u03b1 expression marks hepatocyte differentiation; loss linked to HCC.", "protein": "HNF4\u03b1", "protein_enriched": { "function": "Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promot", "gene_name": "HNF4A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41235" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates Lgr5 cell surface expression.", "mechanism": "Lgr5+ stem cells contribute to liver regeneration and fibrosis.", "protein": "Lgr5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "N-glycosylation required for BSEP trafficking and function.", "mechanism": "BSEP dysfunction leads to bile accumulation and hepatotoxicity.", "protein": "Bile salt export pump (BSEP)", "protein_enriched": { "function": "Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore par", "gene_name": "ABCB11", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "O95342" }, "relationship_type": "causal", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "Phase II enzymes detoxify alcohol metabolites.", "protein": "Phase II enzymes (e.g., UGTs)", "relationship_type": "protective", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Metabolic dysfunction-associated steatotic liver disease (MASLD)", "glycan_involvement": "Glycosylation modulates transporter localization and function.", "mechanism": "Transporter dysfunction impairs lipid and glucose metabolism.", "protein": "Membrane transporters", "relationship_type": "causal", "source_pmcid": "PMC12214119" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycogen structure and association with glycoproteins affect storage.", "mechanism": "Altered glycogen accumulation reflects impaired glucose metabolism.", "protein": "Glycogen", "relationship_type": "biomarker", "source_pmcid": "PMC12214119" }, { "confidence": "low", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may affect viral protein stability.", "mechanism": "HSVtk expression enables selective hepatocyte ablation in models.", "protein": "UL23 (HSVtk)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214119" }, { "confidence": "high", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "N-glycosylation in extracellular domain modulates receptor stability and function.", "mechanism": "Upregulation and activation of P2X7 receptor in CNS glial cells leads to neuroinflammation, oxidative stress, and mitochondrial dysfunction, contributing to ASD pathogenesis.", "protein": "P2X7 receptor", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12214281" }, { "confidence": "high", "disease": "Maternal Immune Activation (MIA)-induced neurodevelopmental disorder", "glycan_involvement": "Glycosylation affects receptor trafficking and immune signaling.", "mechanism": "Activation in maternal immune cells increases cytokine release (IL-6, TNF\u03b1), crossing placenta and disrupting fetal neurodevelopment.", "protein": "P2X7 receptor", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12214281" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for proper receptor folding and surface expression.", "mechanism": "ATP-mediated activation triggers NLRP3 inflammasome assembly, leading to increased IL-1\u03b2 and IL-18 secretion.", "protein": "P2X7 receptor", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12214281" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation modulates receptor channel properties.", "mechanism": "Ca2+ influx via P2X7 receptor impairs mitochondrial electron transport chain, increasing ROS and causing dysfunction.", "protein": "P2X7 receptor", "relationship_type": "causal", "source_pmcid": "PMC12214281" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation may affect receptor-mediated redox signaling.", "mechanism": "Activation increases NOX2-mediated superoxide production and reduces antioxidant enzyme activity.", "protein": "P2X7 receptor", "relationship_type": "causal", "source_pmcid": "PMC12214281" }, { "confidence": "high", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "Glycosylation required for cytokine secretion and stability.", "mechanism": "Elevated plasma IL-1\u03b2 correlates with ASD severity; produced downstream of P2X7/NLRP3 activation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12214281" }, { "confidence": "high", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "Glycosylation essential for cytokine function.", "mechanism": "Maternal IL-6 crosses placenta, disrupts fetal neurodevelopment, and is elevated in ASD.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12214281" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder (ASD)", "glycan_involvement": "Glycosylation required for cytokine activity.", "mechanism": "Upregulated in ASD patients; produced via P2X7/NLRP3 pathway, contributes to neuroinflammation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12214281" }, { "confidence": "medium", "disease": "Oxidative stress in ASD", "glycan_involvement": "Glycosylation affects NOX2 membrane localization and activity.", "mechanism": "P2X7 activation increases NOX2 activity, leading to superoxide generation and oxidative stress in ASD brain.", "protein": "NOX2", "relationship_type": "causal", "source_pmcid": "PMC12214281" }, { "confidence": "medium", "disease": "Oxidative stress in ASD", "glycan_involvement": "Glycosylation required for enzyme stability and activity.", "mechanism": "GPx activity is reduced in ASD, correlating with increased oxidative stress and symptom severity.", "protein": "GPx", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12214281" }, { "confidence": "high", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Autoantibodies against PLA2R cause immune complex deposition in glomeruli.", "protein": "PLA2R", "protein_enriched": { "function": "Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response (PubMed:10066756, PubMed:16371369, PubMed:17090529, Pu", "gene_name": "PLA2G7", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q13093" }, "relationship_type": "causal", "source_pmcid": "PMC12214870" }, { "confidence": "high", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Autoantibodies against THSD7A lead to glomerular immune deposits.", "protein": "THSD7A", "relationship_type": "causal", "source_pmcid": "PMC12214870" }, { "confidence": "medium", "disease": "Neoplastic disease (malignancy)", "glycan_involvement": "Glycosylation may affect tumor antigenicity.", "mechanism": "THSD7A-associated MN is frequently linked to underlying malignancy.", "protein": "THSD7A", "relationship_type": "biomarker", "source_pmcid": "PMC12214870" }, { "confidence": "high", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Glycosylation may influence immune complex formation.", "mechanism": "NELL1 is a target antigen in MN; autoantibodies drive disease.", "protein": "NELL1", "relationship_type": "causal", "source_pmcid": "PMC12214870" }, { "confidence": "high", "disease": "Lupus nephritis", "glycan_involvement": "Glycosylation involved in antigen presentation.", "mechanism": "EXT1/EXT2 antigens are associated with lupus-related MN.", "protein": "EXT1/EXT2", "relationship_type": "biomarker", "source_pmcid": "PMC12214870" }, { "confidence": "high", "disease": "Lupus nephritis", "glycan_involvement": "Polysialylation modulates immune recognition.", "mechanism": "NCAM1 is a target antigen in lupus-associated MN.", "protein": "NCAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12214870" }, { "confidence": "medium", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Likely involved in immune complex formation.", "mechanism": "Identified as a putative antigen in MN; mechanism unclear.", "protein": "PGLYRP1", "relationship_type": "putative causal", "source_pmcid": "PMC12214870" }, { "confidence": "medium", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Modifies heparan sulfate glycosaminoglycans.", "mechanism": "Identified as a putative antigen in MN; mechanism unclear.", "protein": "SULF1", "relationship_type": "putative causal", "source_pmcid": "PMC12214870" }, { "confidence": "low", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Acts on hyaluronan, a glycosaminoglycan.", "mechanism": "Novel antigen in MN; HYAL1 degrades hyaluronic acid, may affect glomerular matrix.", "protein": "HYAL1", "relationship_type": "putative causal", "source_pmcid": "PMC12214870" }, { "confidence": "low", "disease": "Membranous nephropathy (MN)", "glycan_involvement": "Glycosylation affects secretion and cell interactions.", "mechanism": "Novel antigen in MN; THBS1 involved in podocyte injury and proteinuria.", "protein": "THBS1", "relationship_type": "putative causal", "source_pmcid": "PMC12214870" }, { "confidence": "high", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "Light chains are glycoproteins; glycosylation can influence aggregation and amyloidogenicity.", "mechanism": "Misfolded immunoglobulin light chains aggregate into amyloid fibrils, depositing in myocardium.", "protein": "Immunoglobulin light chain", "relationship_type": "causal", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "As an IgG1 antibody, glycosylation affects Fc-mediated effector functions.", "mechanism": "Daratumumab targets CD38 on plasma cells, reducing production of amyloidogenic light chains.", "protein": "Daratumumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214942" }, { "confidence": "medium", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "CD38 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "CD38 is highly expressed on clonal plasma cells producing amyloidogenic light chains; targeted by daratumumab.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "Glycosylation status can affect detection and pathogenicity.", "mechanism": "Serum free light chain levels reflect disease burden and response to therapy.", "protein": "Immunoglobulin free light chain", "relationship_type": "biomarker", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation may affect stability and clearance.", "mechanism": "Elevated NT-proBNP indicates cardiac dysfunction and is used for staging and monitoring response.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214942" }, { "confidence": "medium", "disease": "Light-chain cardiac amyloidosis (LCCA)", "glycan_involvement": "cTnI is glycosylated; glycosylation may influence assay performance.", "mechanism": "Elevated cTnI reflects myocardial injury in LCCA.", "protein": "Cardiac troponin I (cTnI)", "protein_enriched": { "function": "With S4 and S5 plays an important role in translational accuracy. Located at the interface of the 30S and 50S subunits (By similarity)", "gene_name": "rps12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19461" }, "relationship_type": "biomarker", "source_pmcid": "PMC12214942" }, { "confidence": "medium", "disease": "Multiple myeloma", "glycan_involvement": "Heavily glycosylated; glycan chains modulate cell adhesion and signaling.", "mechanism": "CD138 marks plasma cells; used in diagnosis and monitoring of plasma cell disorders.", "protein": "CD138 (Syndecan-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation may affect amyloidogenicity and tissue deposition.", "mechanism": "Amyloid deposition in myocardium leads to restrictive cardiomyopathy and heart failure.", "protein": "Immunoglobulin light chain", "relationship_type": "causal", "source_pmcid": "PMC12214942" }, { "confidence": "medium", "disease": "Cardiac arrhythmias", "glycan_involvement": "Glycosylation may influence aggregation and tissue tropism.", "mechanism": "Amyloid infiltration disrupts cardiac conduction system.", "protein": "Immunoglobulin light chain", "relationship_type": "causal", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "IgG1 glycosylation modulates ADCC/CDC activity.", "mechanism": "Targets CD38 on malignant plasma cells, reducing tumor burden.", "protein": "Daratumumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12214942" }, { "confidence": "high", "disease": "Hepatic angiosarcoma (HAS)", "glycan_involvement": "CD34 is a heavily glycosylated sialomucin; glycosylation is essential for its cell surface localization and function.", "mechanism": "CD34 is expressed on tumor endothelial cells and used for pathological diagnosis of HAS.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215201" }, { "confidence": "high", "disease": "Hepatic angiosarcoma (HAS)", "glycan_involvement": "Factor VIII is glycosylated, which affects its stability and secretion.", "mechanism": "Factor VIII-related antigen is expressed in tumor cells, aiding in the diagnosis of HAS.", "protein": "Factor VIII-related antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12215201" }, { "confidence": "high", "disease": "Angiosarcoma (AS)", "glycan_involvement": "Glycosylation of CD34 modulates its adhesive properties and cell signaling.", "mechanism": "CD34 positivity is used to identify AS in various tissues.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12215201" }, { "confidence": "high", "disease": "Angiosarcoma (AS)", "glycan_involvement": "Glycosylation is required for Factor VIII function and antigenicity.", "mechanism": "Factor VIII-related antigen is a marker for endothelial origin in AS.", "protein": "Factor VIII-related antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12215201" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation affects Factor VIII activity in coagulation cascades.", "mechanism": "Tumor-derived Factor VIII may contribute to coagulopathy in advanced HAS, leading to DIC.", "protein": "Factor VIII-related antigen", "relationship_type": "causal", "source_pmcid": "PMC12215201" }, { "confidence": "high", "disease": "Pulmonary Hypertension", "glycan_involvement": "Hydroxylysine glycosylation at cross-linking sites modulates cross-link formation and peptide heterogeneity.", "mechanism": "NTX peptide levels are increased in pulmonary hypertension, reflecting enhanced collagen cross-linking and vascular stiffening.", "protein": "Type I Collagen (NTX peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC12216727" }, { "confidence": "high", "disease": "Fibrotic Disease", "glycan_involvement": "LOX acts on hydroxylysine, which can be glycosylated, affecting cross-linking efficiency.", "mechanism": "LOX-mediated collagen cross-linking increases tissue stiffness, promoting fibrosis.", "protein": "Lysyl Oxidase (LOX)", "relationship_type": "causal", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Tumor Progression", "glycan_involvement": "Glycosylation of collagen modulates LOX substrate availability.", "mechanism": "LOX activity remodels ECM, facilitating tumor invasion and metastasis.", "protein": "Lysyl Oxidase (LOX)", "relationship_type": "causal", "source_pmcid": "PMC12216727" }, { "confidence": "high", "disease": "Bone and Connective Tissue Turnover Disorders", "glycan_involvement": "Hydroxylysine glycosylation influences NTX peptide heterogeneity.", "mechanism": "NTX is a clinical marker for bone and connective tissue turnover.", "protein": "Type I Collagen (NTX peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Metastasis", "glycan_involvement": "Collagen glycosylation may affect LOX-mediated cross-linking.", "mechanism": "LOX preconditions distant organs for metastatic dissemination by remodeling ECM.", "protein": "Lysyl Oxidase (LOX)", "relationship_type": "causal", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Hydroxylysine can be glycosylated, affecting cross-linking.", "mechanism": "Increased LH1 in PH enhances hydroxylysine formation, promoting cross-linking and vascular stiffening.", "protein": "Lysyl Hydroxylase (PLOD1/LH1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Acts on glycosylated hydroxylysine residues.", "mechanism": "LOXL1 upregulation in PH contributes to increased collagen cross-linking.", "protein": "LOX-like 1 (LOXL1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Age-dependent changes in glycosylation patterns affect NTX forms.", "mechanism": "NTX peptide heterogeneity reflects age-related ECM remodeling.", "protein": "Type I Collagen (NTX peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC12216727" }, { "confidence": "medium", "disease": "Wound Healing", "glycan_involvement": "Glycosylation state influences peptide detectability.", "mechanism": "NTX peptides indicate ECM remodeling during wound healing.", "protein": "Type I Collagen (NTX peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC12216727" }, { "confidence": "high", "disease": "Fibrotic Disease", "glycan_involvement": "Glycosylation of hydroxylysine residues modulates cross-linking and peptide diversity.", "mechanism": "NTX peptide abundance and heterogeneity are increased in fibrosis due to enhanced cross-linking.", "protein": "Type I Collagen (NTX peptide)", "relationship_type": "biomarker", "source_pmcid": "PMC12216727" }, { "confidence": "high", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "FimH binds to mannose residues on host glycoproteins.", "mechanism": "FimH mediates adhesion of E. coli to uroepithelial cells via mannose-specific binding, facilitating colonization.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Pyelonephritis", "glycan_involvement": "P fimbriae bind to Gal(\u03b11-4)Gal moieties on host glycoproteins.", "mechanism": "PapC is essential for assembly of P fimbriae, which mediate adhesion to kidney epithelial cells, promoting upper UTI.", "protein": "PapC", "protein_enriched": { "function": "Required for the biogenesis of type 1 fimbriae. Binds and interact with FimH", "gene_name": "fimC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P31697" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "medium", "disease": "Multidrug-resistant UTI", "glycan_involvement": "FimH-mannose interaction enhances biofilm formation.", "mechanism": "High prevalence of fimH gene in MDR UPEC isolates; associated with increased colonization and persistence.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "biomarker", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Multidrug-resistant UTI", "glycan_involvement": "P fimbriae-glycan binding may enhance resistance via biofilm formation.", "mechanism": "Presence of papC gene is significantly associated with reduced cefotaxime susceptibility.", "protein": "PapC", "protein_enriched": { "function": "Required for the biogenesis of type 1 fimbriae. Binds and interact with FimH", "gene_name": "fimC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P31697" }, "relationship_type": "biomarker", "source_pmcid": "PMC12218877" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Indirect; may interact with glycosylated host cell surfaces.", "mechanism": "HlyA (alpha-hemolysin) damages host tissues and evades immune response, promoting infection.", "protein": "HlyA", "protein_enriched": { "function": "Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture by forming a pore", "gene_name": "hlyA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09983" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Multidrug-resistant UTI", "glycan_involvement": "Biofilm matrix contains glycoproteins and exopolysaccharides.", "mechanism": "Biofilm formation is significantly correlated with multidrug resistance, protecting bacteria from antibiotics.", "protein": "Biofilm matrix proteins", "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "medium", "disease": "Diabetes-associated UTI", "glycan_involvement": "Altered host glycosylation in diabetes may increase FimH binding.", "mechanism": "FimH-mediated adhesion may be enhanced in diabetic patients due to altered glycosylation of uroepithelial cells.", "protein": "FimH", "protein_enriched": { "function": "Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally posi", "gene_name": "fimH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08191" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Binds to specific glycan receptors on uroepithelial cells.", "mechanism": "PapC facilitates colonization and persistence in urinary tract via P fimbriae assembly.", "protein": "PapC", "protein_enriched": { "function": "Required for the biogenesis of type 1 fimbriae. Binds and interact with FimH", "gene_name": "fimC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P31697" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "medium", "disease": "Pyelonephritis", "glycan_involvement": "Potential interaction with glycosylated host cell membranes.", "mechanism": "HlyA contributes to tissue damage in upper urinary tract infections.", "protein": "HlyA", "protein_enriched": { "function": "Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture by forming a pore", "gene_name": "hlyA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09983" }, "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Biofilm matrix includes glycoproteins and polysaccharides.", "mechanism": "Biofilm formation facilitates chronic and recurrent UTIs by protecting bacteria from host defenses.", "protein": "Biofilm matrix proteins", "relationship_type": "causal", "source_pmcid": "PMC12218877" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its clearance and function.", "mechanism": "Elevated LDL is a risk factor for cardiovascular disease; probiotics reduced LDL levels.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates LDL receptor binding and metabolism.", "mechanism": "High-fat diet increases LDL; probiotics lower LDL, correlating with reduced obesity risk.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated ALP indicates liver inflammation; probiotics reduced ALP levels.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is glycosylated; glycosylation may affect its serum half-life.", "mechanism": "ALT elevation is a marker of NAFLD; probiotics reduced ALT in treated rats.", "protein": "Glutamate pyruvate transaminase (ALT/SGPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is glycosylated; glycosylation may influence its activity.", "mechanism": "AST elevation is a marker of liver injury; probiotics reduced AST in treated rats.", "protein": "Glutamic-oxaloacetic transaminase (AST/SGOT)", "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "LDL glycosylation affects hepatic uptake.", "mechanism": "High LDL contributes to hepatic lipid deposition; probiotics lowered LDL and hepatic fat.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates ALP function in liver disease.", "mechanism": "ALP is elevated in NAFLD; probiotics reduced ALP.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "LDL glycosylation influences inflammatory signaling.", "mechanism": "LDL accumulation promotes liver inflammation; probiotics reduced LDL and inflammation.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation may affect ALT release and detection.", "mechanism": "ALT is released during hepatocyte injury; probiotics reduced ALT, indicating less inflammation.", "protein": "Glutamate pyruvate transaminase (ALT/SGPT)", "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation may affect AST stability.", "mechanism": "AST is released during liver injury; probiotics reduced AST, indicating improved liver health.", "protein": "Glutamic-oxaloacetic transaminase (AST/SGOT)", "relationship_type": "biomarker", "source_pmcid": "PMC12218888" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation is required for IL-10 stability and secretion; functional glycosylation is necessary for bioactivity.", "mechanism": "IL-10 suppresses inflammatory cytokine expression and promotes M2 macrophage polarization, reducing kidney inflammation and injury.", "protein": "Interleukin-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation is important for catalase stability and activity.", "mechanism": "Catalase scavenges reactive oxygen species (ROS), reducing oxidative stress in kidney tubular epithelial cells.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Kidney Inflammation", "glycan_involvement": "N-glycosylation supports proper folding and secretion.", "mechanism": "IL-10 reduces pro-inflammatory cytokine expression and inhibits M1 macrophage polarization.", "protein": "Interleukin-10", "relationship_type": "protective", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Kidney Inflammation", "glycan_involvement": "N-glycosylation supports enzyme stability.", "mechanism": "Catalase reduces ROS, indirectly limiting inflammation.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12219372" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "IL-10 modulates immune response, potentially slowing progression from AKI to CKD.", "protein": "Interleukin-10", "relationship_type": "protective", "source_pmcid": "PMC12219372" }, { "confidence": "medium", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation affects serum half-life and detection.", "mechanism": "IL-10 levels reflect anti-inflammatory response in AKI.", "protein": "Interleukin-10", "relationship_type": "biomarker", "source_pmcid": "PMC12219372" }, { "confidence": "medium", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation affects enzyme stability and serum levels.", "mechanism": "Catalase activity indicates antioxidant defense status in AKI.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation required for bioactivity and delivery.", "mechanism": "Co-delivery with catalase enhances therapeutic effect by simultaneously reducing inflammation and oxidative stress.", "protein": "Interleukin-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "N-glycosylation required for enzyme function.", "mechanism": "Co-delivery with IL-10 enhances efficacy by supporting M2 macrophage polarization and reducing ROS.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Kidney Inflammation", "glycan_involvement": "N-glycosylation critical for stability and activity.", "mechanism": "Targeted delivery reduces systemic immunosuppression risk and enhances local anti-inflammatory effect.", "protein": "Interleukin-10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12219372" }, { "confidence": "high", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation of viral envelope proteins is essential for host cell entry and immune evasion.", "mechanism": "Persistent measles virus infection in CNS, mediated by viral glycoproteins, leads to progressive neurodegeneration.", "protein": "Measles Virus Glycoproteins (Hemagglutinin, Fusion protein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12220887" }, { "confidence": "high", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "IgG glycosylation affects antibody function and CNS penetration.", "mechanism": "Elevated anti-measles IgG in CSF and blood is diagnostic for SSPE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12220887" }, { "confidence": "high", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation modulates IgG aggregation and immune response.", "mechanism": "Multiple oligoclonal IgG bands in CSF indicate intrathecal antibody synthesis in SSPE.", "protein": "Oligoclonal Bands (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12220887" }, { "confidence": "medium", "disease": "Autoimmune Encephalitis", "glycan_involvement": "MOG is a CNS glycoprotein; glycosylation affects antigenicity.", "mechanism": "Anti-MOG antibodies are used to exclude autoimmune encephalitis in SSPE differential diagnosis.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC12220887" }, { "confidence": "medium", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation influences IFN-\u03b1 stability and receptor binding.", "mechanism": "IFN-\u03b1 therapy can induce temporary remission in SSPE by modulating immune response.", "protein": "Interferon-alpha (IFN-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12220887" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation impacts IgG efficacy and half-life.", "mechanism": "Measles vaccination induces protective IgG antibodies, preventing infection and SSPE.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12220887" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "N-glycosylation is critical for viral infectivity.", "mechanism": "Viral glycoproteins mediate host cell entry and systemic infection.", "protein": "Measles Virus Glycoproteins (Hemagglutinin, Fusion protein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12220887" }, { "confidence": "medium", "disease": "Autoimmune Encephalitis", "glycan_involvement": "Glycosylation modulates autoantibody pathogenicity.", "mechanism": "Autoantibodies (IgG) against CNS glycoproteins are diagnostic for autoimmune encephalitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12220887" }, { "confidence": "medium", "disease": "Demyelination", "glycan_involvement": "Glycosylation of viral proteins affects immune recognition and CNS persistence.", "mechanism": "Chronic measles virus infection leads to demyelination via immune-mediated mechanisms.", "protein": "Measles Virus Glycoproteins (Hemagglutinin, Fusion protein)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12220887" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "IgG glycosylation may influence CNS effects.", "mechanism": "Elevated anti-measles IgG in CSF is associated with SSPE-related epilepsy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12220887" }, { "confidence": "high", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Netrin-1 is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated NT-1 in cord blood correlates with severity of HIE; aids early diagnosis and decision for therapeutic hypothermia.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "biomarker", "source_pmcid": "PMC12220919" }, { "confidence": "high", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "NSE is glycosylated; glycosylation may influence its release during neuronal injury.", "mechanism": "Elevated NSE in cord blood correlates with severity of HIE; highly sensitive and specific for moderate/severe HIE.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Glycosylation may modulate NT-1's interaction with extracellular matrix and receptors.", "mechanism": "NT-1 helps maintain blood-brain barrier integrity after injury.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "protective", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Cerebral ischemic stroke", "glycan_involvement": "Glycosylation may affect NT-1's signaling and stability.", "mechanism": "NT-1 contributes to astrocyte activation and inflammation; potential target for stroke therapy.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Subarachnoid hemorrhage (SAH)", "glycan_involvement": "Glycosylation may influence NT-1's neuroprotective functions.", "mechanism": "NT-1 reduces brain edema, improves neurological status, and decreases neural apoptosis in animal models.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "protective", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Experimental autoimmune encephalomyelitis", "glycan_involvement": "Glycosylation may affect NT-1's barrier-protective properties.", "mechanism": "NT-1 maintains blood-brain barrier integrity during neuroinflammation.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "protective", "source_pmcid": "PMC12220919" }, { "confidence": "high", "disease": "Perinatal asphyxia", "glycan_involvement": "Glycosylation may influence NSE release and detection.", "mechanism": "Elevated NSE indicates neuronal injury following hypoxic insult.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Glycosylation may be critical for NT-1's therapeutic efficacy.", "mechanism": "Potential for NT-1 to reduce ischemic damage and protect BBB in HIE.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12220919" }, { "confidence": "high", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Glycosylation may affect NSE's stability in circulation.", "mechanism": "NSE levels predict severity and prognosis of HIE; higher levels associated with poor outcomes.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Glycosylation may influence NT-1's biomarker performance.", "mechanism": "NT-1 levels may predict severity and outcome in HIE.", "protein": "Netrin-1", "protein_enriched": { "function": "Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to", "gene_name": "NTN1", "glycan_count": 4, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G91636VS", "G57321FI", "G02815KT" ], "uniprot_id": "O95631" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12220919" }, { "confidence": "medium", "disease": "Acute subjective tinnitus (AST)", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "TNF-\u03b1 secretion contributes to cochlear hair cell damage and inflammation, promoting tinnitus.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Acute subjective tinnitus (AST)", "glycan_involvement": "Receptor glycosylation modulates ligand binding and cellular localization.", "mechanism": "Steroid binding to inner ear glucocorticoid receptors suppresses inflammation and protects cochlear cells.", "protein": "Corticosteroid receptor (Glucocorticoid receptor, NR3C1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Acute subjective tinnitus (AST)", "glycan_involvement": "Glycosylation is essential for membrane protein stability and auditory transduction.", "mechanism": "Damage or altered function of membrane glycoproteins impairs cochlear signaling, leading to tinnitus.", "protein": "Cochlear hair cell membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "low", "disease": "Endolymphatic hydrops", "glycan_involvement": "Glycosylation patterns may influence antigenicity and immune recognition.", "mechanism": "Autoimmune response against sac glycoproteins may cause hydrops and low-tone hearing loss.", "protein": "Endolymphatic sac glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Sudden sensorineural hearing loss (SSNHL)", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 activity and receptor interactions.", "mechanism": "TNF-\u03b1 mediated inflammation damages cochlear cells, contributing to SSNHL.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Sudden sensorineural hearing loss (SSNHL)", "glycan_involvement": "Glycosylation affects receptor function and steroid responsiveness.", "mechanism": "Steroid activation of receptor reduces cochlear inflammation and promotes recovery.", "protein": "Corticosteroid receptor (Glucocorticoid receptor, NR3C1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221516" }, { "confidence": "low", "disease": "Cochlear synaptopathy (hidden hearing loss)", "glycan_involvement": "Glycosylation critical for synaptic protein trafficking and function.", "mechanism": "Synaptic glycoprotein dysfunction leads to impaired auditory signaling despite normal audiometry.", "protein": "Cochlear hair cell membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "low", "disease": "Acute subjective tinnitus (AST)", "glycan_involvement": "Altered glycosylation may increase immune targeting.", "mechanism": "Immune-mediated damage to sac glycoproteins may contribute to tinnitus pathogenesis.", "protein": "Endolymphatic sac glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Sudden sensorineural hearing loss (SSNHL)", "glycan_involvement": "Glycosylation maintains hair cell integrity and function.", "mechanism": "Acute damage to hair cell glycoproteins impairs hearing and may cause tinnitus.", "protein": "Cochlear hair cell membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12221516" }, { "confidence": "low", "disease": "Endolymphatic hydrops", "glycan_involvement": "Glycosylation modulates receptor activity in immune cells.", "mechanism": "Steroid activation of receptor may reduce immune-mediated hydrops.", "protein": "Corticosteroid receptor (Glucocorticoid receptor, NR3C1)", "relationship_type": "protective", "source_pmcid": "PMC12221516" }, { "confidence": "medium", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "Glycosylation affects secretion and stability of PAPP-A.", "mechanism": "Circulating PAPP-A levels associated with CMD in HFpEF, reflecting vascular remodeling and inflammation.", "protein": "PAPP-A", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "medium", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "N-glycosylation modulates CD93 function in endothelium.", "mechanism": "CD93 is involved in endothelial cell adhesion and angiogenesis; altered levels linked to CMD.", "protein": "CD93", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "medium", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "Glycosylation regulates EpCAM-mediated cell interactions.", "mechanism": "EpCAM implicated in cell adhesion; altered expression in CMD.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "O-glycosylation affects BNP processing and plasma levels.", "mechanism": "BNP is a diagnostic and prognostic marker for HF; reflects cardiac wall stress.", "protein": "BNP/NPPB", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "N-glycosylation required for IL6 secretion and receptor binding.", "mechanism": "IL6 is a pro-inflammatory cytokine elevated in HF, contributing to cardiac remodeling.", "protein": "IL6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221655" }, { "confidence": "medium", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "CCL20 mediates leukocyte recruitment and inflammation in CMD.", "protein": "CCL20", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "medium", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "Glycosylation influences receptor binding.", "mechanism": "TNFSF14 involved in immune signaling; associated with CMD.", "protein": "TNFSF14", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "medium", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation affects TGM2 secretion and activity.", "mechanism": "TGM2 involved in cardiac fibrosis and remodeling.", "protein": "TGM2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221655" }, { "confidence": "low", "disease": "Coronary microvascular dysfunction (CMD)", "glycan_involvement": "Glycosylation modulates protease activity.", "mechanism": "PRTN3 is a neutrophil serine protease; elevated in CMD.", "protein": "PRTN3", "relationship_type": "biomarker", "source_pmcid": "PMC12221655" }, { "confidence": "low", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation may affect PI3K signaling components.", "mechanism": "PIK3CA is part of PI3K pathway; dysregulation contributes to cardiac hypertrophy.", "protein": "PIK3CA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221655" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "CD44 is a heavily glycosylated cell surface receptor; glycosylation is essential for ligand binding and cell targeting.", "mechanism": "CD44 is overexpressed on activated hepatic stellate cells (aHSCs), enabling targeted delivery of nanodrugs to induce senescence and reduce fibrosis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221764" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "ICAM1 is N-glycosylated, which modulates its cell adhesion and signaling properties.", "mechanism": "ICAM1 is upregulated as part of the senescence-associated secretory phenotype (SASP) in aHSCs, promoting inflammation and fibrosis.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12221764" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "IL-6 is glycosylated, affecting its secretion and stability.", "mechanism": "IL-6 is a SASP cytokine secreted by senescent aHSCs, driving inflammation and fibrogenesis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "IL-8 glycosylation modulates its chemotactic activity.", "mechanism": "IL-8 is a SASP cytokine from senescent aHSCs, promoting inflammatory cell recruitment and fibrosis.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "causal", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "IL-11 is glycosylated, influencing its receptor binding.", "mechanism": "IL-11 is a SASP cytokine contributing to fibrogenic signaling in the liver.", "protein": "IL-11", "protein_enriched": { "function": "Cytokine that stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production (PubMed:214557", "gene_name": "IL11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20809" }, "relationship_type": "causal", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "GM-CSF glycosylation affects its bioactivity.", "mechanism": "GM-CSF is a SASP cytokine from senescent aHSCs, enhancing immune cell recruitment and inflammation.", "protein": "GM-CSF", "relationship_type": "causal", "source_pmcid": "PMC12221764" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagens are glycoproteins; glycosylation affects fibril formation and stability.", "mechanism": "Col1a1 is overproduced by aHSCs, leading to excessive ECM deposition and fibrosis.", "protein": "Col1a1", "relationship_type": "biomarker", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates collagen assembly.", "mechanism": "Col3a1 is upregulated in fibrotic livers, contributing to ECM accumulation.", "protein": "Col3a1", "relationship_type": "biomarker", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences collagen interactions.", "mechanism": "Col5a1 is increased in aHSCs during fibrosis, supporting ECM structure.", "protein": "Col5a1", "relationship_type": "biomarker", "source_pmcid": "PMC12221764" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation of CD44 is linked to tumor progression.", "mechanism": "CD44-mediated signaling and SASP spread from aHSCs may promote carcinogenesis in chronic liver disease.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12221764" }, { "confidence": "high", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "N-glycosylation of gD is essential for receptor binding and infectivity.", "mechanism": "HSV-1 gD mediates viral entry into hepatocytes, leading to hepatitis.", "protein": "Herpes simplex virus glycoprotein D (gD)", "protein_enriched": { "function": "V region of the variable domain of T cell receptor (TR) alpha chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are", "gene_name": "TRAV29DV5", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04437" }, "relationship_type": "causal", "source_pmcid": "PMC12221830" }, { "confidence": "high", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "N-glycosylation modulates gB structure and immune evasion.", "mechanism": "gB facilitates membrane fusion and viral spread in liver tissue.", "protein": "Herpes simplex virus glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC12221830" }, { "confidence": "medium", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "N-glycosylation affects gH/gL complex formation and function.", "mechanism": "gH/gL complex is required for HSV-1 entry and cell-cell fusion in hepatic cells.", "protein": "Herpes simplex virus glycoprotein H (gH)", "protein_enriched": { "function": "Chemokine-binding protein that inhibits neutrophils' chemotaxis", "gene_name": "gG", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P06484" }, "relationship_type": "causal", "source_pmcid": "PMC12221830" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation shields viral proteins from immune detection.", "mechanism": "HSV-1 glycoproteins mediate hepatocyte infection, leading to cytolysis and liver failure.", "protein": "HSV-1 envelope glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC12221830" }, { "confidence": "high", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated AST reflects hepatocyte damage due to HSV-1 infection.", "protein": "Human aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12221830" }, { "confidence": "high", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "Glycosylation influences ALT secretion and activity.", "mechanism": "ALT elevation is a marker of hepatic cytolysis in HH.", "protein": "Human alanine aminotransferase (ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12221830" }, { "confidence": "medium", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "Glycosylation modulates CRP's immune functions.", "mechanism": "CRP is elevated as an acute phase reactant in HH.", "protein": "Human C-reactive protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12221830" }, { "confidence": "medium", "disease": "Herpes simplex virus-associated hepatitis (HH)", "glycan_involvement": "Glycosylation affects LDH stability.", "mechanism": "LDH elevation indicates tissue damage during HH.", "protein": "Human lactate dehydrogenase (LDH)", "relationship_type": "biomarker", "source_pmcid": "PMC12221830" }, { "confidence": "medium", "disease": "Macrophage activation syndrome", "glycan_involvement": "Glycosylation regulates ferritin secretion and immune signaling.", "mechanism": "Hyperferritinaemia is a marker of macrophage activation and systemic inflammation.", "protein": "Human ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC12221830" }, { "confidence": "low", "disease": "Acute renal failure", "glycan_involvement": "Glycosylation of gD may affect tissue tropism.", "mechanism": "HSV-1 infection may contribute to renal injury via systemic inflammation.", "protein": "Herpes simplex virus glycoprotein D (gD)", "protein_enriched": { "function": "V region of the variable domain of T cell receptor (TR) alpha chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are", "gene_name": "TRAV29DV5", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04437" }, "relationship_type": "causal", "source_pmcid": "PMC12221830" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Altered fucosylation (e.g., Le x, Le y, Le a, Le b) on tumor cell surfaces.", "mechanism": "FTLs bind aberrant fucosylated glycans (e.g., Lewis antigens) upregulated in tumors; can be used for detection or targeted therapy.", "protein": "F-type lectins (FTLs)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221842" }, { "confidence": "high", "disease": "Streptococcal infections", "glycan_involvement": "Recognition of fucosylated Lewis y and Lewis b moieties on host cells.", "mechanism": "Lectinolysin binds host cell fucosylated Lewis antigens, forms pores, causes cell lysis.", "protein": "Lectinolysin (Streptococcus mitis cytolysin)", "relationship_type": "causal", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Binds to fucosylated glycans on cancer cells.", "mechanism": "Induces apoptosis in human cancer cells by downregulating anti-apoptosis factors.", "protein": "DlFBL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Viral hemorrhagic septicemia", "glycan_involvement": "Likely recognizes viral or host fucosylated glycans.", "mechanism": "Controls viral budding, limiting infection.", "protein": "RbFTL-3", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "high", "disease": "Bacterial infections (e.g., Vibrio, E. coli)", "glycan_involvement": "Binds to bacterial surface glycans (LPS, peptidoglycan).", "mechanism": "Agglutinates and binds bacteria, upregulated upon infection.", "protein": "AjFTL-1/AjFTL-2", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Fertilization disorders (e.g., polyspermia)", "glycan_involvement": "Binds to egg surface fucosylated glycans.", "mechanism": "Mediates species-specific sperm-egg recognition, preventing polyspermy.", "protein": "Bindins", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Bacterial infections (e.g., Vibrio)", "glycan_involvement": "Binds to bacterial fucosylated glycans.", "mechanism": "Upregulated upon infection, involved in innate immune response.", "protein": "PmF-lectin", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Cell adhesion disorders", "glycan_involvement": "Binds endogenous N-acetyl glucosamine and N-acetyl galactosamine.", "mechanism": "Mediates organelle aggregation and protoplast regeneration after cell damage.", "protein": "Bryohealin", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "medium", "disease": "Exosome biomarker detection", "glycan_involvement": "Altered fucosylation on exosomal glycoproteins.", "mechanism": "FTLs detect aberrant fucosylated glycans in tumor-derived exosomes.", "protein": "FTLs (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12221842" }, { "confidence": "high", "disease": "Innate immune deficiency", "glycan_involvement": "Recognition of pathogen-associated fucosylated glycans.", "mechanism": "FTLs act as opsonins, promoting phagocytosis of pathogens.", "protein": "FTLs (general)", "relationship_type": "protective", "source_pmcid": "PMC12221842" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "As a glycoprotein, may affect protein folding and ER-associated degradation; glycosylation may modulate immune signaling.", "mechanism": "Upregulated in advanced and unstable plaques; associated with immune cell infiltration and macrophage transformation.", "protein": "SEL1L3", "protein_enriched": { "function": "Required for normal progression through mitosis. Involved in chromosome alignment and cytokinesis via regulation of microtubules polymerization", "gene_name": "ANKRD53", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G77277QT", "G23719VF" ], "uniprot_id": "Q8N9V6" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Contains N-glycosylation sites; glycosylation may regulate stability and immune interactions.", "mechanism": "Upregulated in advanced and unstable plaques; promotes macrophage transformation and immune infiltration.", "protein": "PARP14", "protein_enriched": { "function": "ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate residues on target proteins (PubMed:16061477, PubMed:18851833, PubMed:25043379, PubMed:27796300). In contrast to PARP1 and PARP2", "gene_name": "PARP14", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q460N5" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Potential glycosylation may affect cytoskeletal interactions and immune cell signaling.", "mechanism": "Downregulated in advanced/unstable plaques; associated with reduced macrophage infiltration and altered M1/M2 ratio.", "protein": "PDLIM1", "protein_enriched": { "function": "May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both sk", "gene_name": "PDLIM7", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G57321FI", "G70994MS" ], "uniprot_id": "Q9NR12" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12221901" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Binds \u03b2-galactoside glycans on immune receptors (e.g., CD45, CD44, HAVCR2), modulating immune cell migration and inflammation.", "mechanism": "Secreted by senescent vascular cells; mediates macrophage activation via glycan-dependent cell-cell interactions.", "protein": "LGALS9 (Galectin-9)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for surface expression and ligand binding.", "mechanism": "Receptor for MIF; mediates pro-inflammatory signaling in macrophages within plaques.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Heavily glycosylated; glycan structures modulate ligand binding and cell-cell interactions.", "mechanism": "Interacts with galectin-9 and MIF; promotes immune cell adhesion and migration in plaques.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ligand binding and immune regulation.", "mechanism": "Receptor for galectin-9; modulates T cell and macrophage responses in plaques.", "protein": "HAVCR2 (TIM-3)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates galectin binding and signaling.", "mechanism": "Target of galectin-9; modulates immune cell activation in atherosclerotic lesions.", "protein": "CD45 (PTPRC)", "relationship_type": "causal", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect complement activation and immune clearance.", "mechanism": "Marker of C1Q+ (M2-like) macrophages; promotes cholesterol efflux and inflammation resolution.", "protein": "C1QA", "relationship_type": "protective", "source_pmcid": "PMC12221901" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for surface expression and ligand binding.", "mechanism": "Marker of foam cell-like macrophages; associated with lipid accumulation and plaque progression.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12221901" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation stabilizes SOD1 structure and activity.", "mechanism": "Upregulation of SOD1 enhances antioxidant defense, reducing oxidative damage in muscle.", "protein": "SOD1", "relationship_type": "protective", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation affects enzyme stability and plasma half-life.", "mechanism": "GSH-PX detoxifies peroxides, lowering oxidative stress; decreased levels may indicate overload.", "protein": "GSH-PX", "relationship_type": "protective", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Meat quality deterioration", "glycan_involvement": "N-glycosylation modulates antioxidant properties.", "mechanism": "Albumin levels reflect protein status and antioxidant capacity, impacting meat quality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Meat quality deterioration", "glycan_involvement": "Glycosylation influences myosin stability and muscle fiber function.", "mechanism": "Upregulation of MYH1B promotes slow muscle fiber formation, reducing drip loss and improving meat quality.", "protein": "MYH1B", "relationship_type": "protective", "source_pmcid": "PMC12221941" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of apolipoproteins affects TG metabolism.", "mechanism": "Elevated TG is associated with increased risk of cardiovascular disease; FSP lowers TG.", "protein": "Triglyceride-rich lipoproteins (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates FFA transport and clearance.", "mechanism": "High plasma FFA is linked to obesity; FSP reduces FFA levels.", "protein": "Free fatty acids (FFA) carrier proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of LDL affects receptor binding and clearance.", "mechanism": "Elevated LDL-C promotes atherosclerosis; FSP may modulate LDL-C.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC12221941" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation impacts HDL function and cholesterol efflux.", "mechanism": "HDL-C is protective against cardiovascular disease; FSP may influence HDL-C levels.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12221941" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation affects enzyme secretion and stability.", "mechanism": "Elevated AST indicates liver injury; FSP may modulate AST levels.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12221941" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "ALT is a marker of liver health; FSP may influence ALT levels.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12221941" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation modulates IL-6 stability and receptor binding.", "mechanism": "Promotes chondrocyte apoptosis and cartilage matrix degradation via inflammatory signaling.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and bioactivity.", "mechanism": "Induces inflammatory cascades leading to joint degeneration.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "O-glycosylation influences leptin receptor interactions.", "mechanism": "Elevated in synovial fluid; stimulates cartilage catabolism and inflammation.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12221944" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation affects multimerization and anti-inflammatory activity.", "mechanism": "Altered levels in OA; modulates inflammatory response in joint tissues.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221944" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation regulates MMP secretion and activity.", "mechanism": "Degrade cartilage extracellular matrix, accelerating OA progression.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation may modulate inflammasome assembly.", "mechanism": "Activates IL-1\u03b2 processing, perpetuating synovial inflammation.", "protein": "NLRP3 Inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation affects channel localization and function.", "mechanism": "Mechanotransduction in chondrocytes triggers inflammatory signaling.", "protein": "TRPV4", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity", "gene_name": "FOLH1B", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HBA9" }, "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation modulates mechanosensitivity.", "mechanism": "Respond to abnormal joint loading, initiating inflammation.", "protein": "Piezo1/2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation influences secretion and receptor binding.", "mechanism": "Elevated in OA; promotes joint inflammation.", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "biomarker", "source_pmcid": "PMC12221944" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Extensive glycosylation critical for cartilage structure and function.", "mechanism": "Loss/degradation leads to cartilage breakdown.", "protein": "Cartilage Matrix Proteins (e.g., Aggrecan)", "relationship_type": "causal", "source_pmcid": "PMC12221944" }, { "confidence": "high", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation mediates axon-glia interaction.", "mechanism": "MAG is downregulated during Schwann cell repair phenotype; persistent expression inhibits regeneration.", "protein": "MAG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222135" }, { "confidence": "high", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "P0 is N-glycosylated, essential for myelin compaction.", "mechanism": "P0 is downregulated during Schwann cell reprogramming; re-expression supports remyelination.", "protein": "P0", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "Polysialylation of NCAM modulates cell-cell interactions during regeneration.", "mechanism": "NCAM is upregulated in non-myelinating/repair Schwann cells, marking regenerative phenotype.", "protein": "NCAM", "relationship_type": "biomarker", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "N-glycosylation affects L1CAM-mediated adhesion.", "mechanism": "L1CAM marks immature/Remak Schwann cells, involved in axonal guidance.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222135" }, { "confidence": "high", "disease": "Charcot-Marie-Tooth disease type 1A (CMT1A)", "glycan_involvement": "PMP22 is glycosylated; glycosylation affects trafficking and stability.", "mechanism": "Overexpression of PMP22 leads to demyelination in CMT1A.", "protein": "PMP22", "protein_enriched": { "function": "Might be involved in growth regulation, and in myelinization in the peripheral nervous system", "gene_name": "PMP22", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q01453" }, "relationship_type": "causal", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Nerve regeneration failure", "glycan_involvement": "N-glycosylation required for transferrin receptor binding.", "mechanism": "Transferrin promotes Schwann cell differentiation and myelination; iron deficiency impairs regeneration.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "Glycosylation required for GDNF secretion and activity.", "mechanism": "GDNF is upregulated in repair Schwann cells, promoting axonal survival and regeneration.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Diabetic neuropathy", "glycan_involvement": "BDNF is glycosylated, affecting secretion and receptor interaction.", "mechanism": "BDNF expression is suppressed in diabetes; restoration (e.g., by TSA) improves regeneration.", "protein": "BDNF", "relationship_type": "protective", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Peripheral nerve injury (PNI)", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "p75 NTR is upregulated in repair Schwann cells, mediating neurotrophin signaling.", "protein": "p75 NTR", "relationship_type": "biomarker", "source_pmcid": "PMC12222135" }, { "confidence": "medium", "disease": "Peripheral nerve damage", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ECM interactions.", "mechanism": "Tenascin-C from fibroblasts binds \u03b21 integrins on Schwann cells, promoting migration and regeneration.", "protein": "Tenascin-C", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222135" }, { "confidence": "high", "disease": "Postoperative pancreatic fistula (POPF)", "glycan_involvement": "Amylase is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated amylase in drain fluid is used to diagnose POPF.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "Clinically relevant postoperative pancreatic fistula (CR-POPF)", "glycan_involvement": "Albumin glycosylation may affect its function and wound healing.", "mechanism": "Low preoperative albumin is a risk factor for CR-POPF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "CR-POPF", "glycan_involvement": "Glycosylation affects ductal structure and healing.", "mechanism": "Soft pancreatic texture and small duct diameter (reflecting glycoprotein composition) increase CR-POPF risk.", "protein": "Pancreatic ductal glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "CR-POPF", "glycan_involvement": "Omental glycoproteins modulate inflammation and angiogenesis.", "mechanism": "Omental reinforcement reduces CR-POPF by promoting healing and isolation.", "protein": "Omental glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "CR-POPF", "glycan_involvement": "VEGF glycosylation is essential for its activity.", "mechanism": "Omental tissue delivers VEGF, enhancing vascularization and healing at anastomosis.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "protective", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "CR-POPF", "glycan_involvement": "Glycosylation modulates macrophage phenotype and function.", "mechanism": "Omental tissue increases M2/M1 ratio, reducing inflammation and promoting healing.", "protein": "Macrophage glycoproteins (M2/M1 markers)", "relationship_type": "protective", "source_pmcid": "PMC12222157" }, { "confidence": "medium", "disease": "Intra-abdominal infection", "glycan_involvement": "Immunoglobulin glycosylation affects immune activity.", "mechanism": "Omental glycoproteins enhance immune response, reducing infection risk.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC12222157" }, { "confidence": "low", "disease": "POPF", "glycan_involvement": "O-glycosylation of mucins is critical for barrier function.", "mechanism": "Altered mucin glycosylation may affect ductal healing and fistula formation.", "protein": "Pancreatic mucins", "relationship_type": "causal", "source_pmcid": "PMC12222157" }, { "confidence": "low", "disease": "Delayed gastric emptying (DGE)", "glycan_involvement": "Glycosylation modulates anti-inflammatory activity.", "mechanism": "Omental glycoproteins reduce local inflammation, lowering DGE risk.", "protein": "Omental anti-inflammatory glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12222157" }, { "confidence": "low", "disease": "Bile leakage", "glycan_involvement": "Bilirubin transport involves glycoproteins.", "mechanism": "Elevated bilirubin in drain fluid indicates bile leakage.", "protein": "Bilirubin (bound to glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12222157" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "BDNF is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "BDNF levels are reduced in schizophrenia; polyphenols increase BDNF, improving neurodevelopment and cognition.", "protein": "Brain-Derived Neurotrophic Factor", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "GAD is glycosylated, which may affect its stability and localization.", "mechanism": "Reduced GAD activity leads to glutamate accumulation; naringenin reverses GAD depletion, normalizing neurotransmission.", "protein": "Glutamic Acid Decarboxylase (GAD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Excitotoxicity", "glycan_involvement": "GS is glycosylated; glycosylation may regulate its degradation.", "mechanism": "Baicalein stabilizes GS, preventing glutamate-induced excitotoxicity.", "protein": "Glutamine Synthetase (GS)", "protein_enriched": { "function": "Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). Its role depends on tissue localization: in ", "gene_name": "GLUL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15104" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "SOD is glycosylated; glycosylation affects enzyme activity.", "mechanism": "Polyphenols increase SOD activity, reducing oxidative stress in schizophrenia.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Oxidative Stress", "glycan_involvement": "CAT is glycosylated; glycosylation influences stability.", "mechanism": "Polyphenols upregulate CAT, mitigating oxidative damage.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates secretion and receptor binding.", "mechanism": "Polyphenols reduce TNF-\u03b1, alleviating neuroinflammation in schizophrenia.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 is glycosylated; glycosylation affects bioactivity.", "mechanism": "Polyphenols lower IL-6, reducing neuroinflammatory symptoms.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "D2 receptor is glycosylated; glycosylation affects receptor function.", "mechanism": "Increased D2 receptor levels linked to schizophrenia; polyphenols modulate dopamine signaling.", "protein": "Dopamine Receptor D2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "D3 receptor is glycosylated; glycosylation impacts ligand binding.", "mechanism": "Elevated D3 receptor affinity for dopamine; polyphenols may modulate receptor activity.", "protein": "Dopamine Receptor D3", "protein_enriched": { "function": "Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation", "gene_name": "DRD3", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35462" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "medium", "disease": "Cognitive Impairment", "glycan_involvement": "TrkB is glycosylated; glycosylation regulates receptor trafficking.", "mechanism": "Curcumin restores TrkB phosphorylation, improving cognition.", "protein": "TrkB (NTRK2)", "protein_enriched": { "function": "Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiati", "gene_name": "NTRK2", "glycan_count": 22, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G02815KT", "G06110VR", "G31852PQ", "G40574BA", "G41247ZX", "G43089EG", "G48414YA", "G62765YT", "G80920RR", "G06356OH", "G00912UN", "G04657PL", "G64394MX", "G72291OX", "G47518TP", "G20312EM", "G82463GQ", "G14796IU", "G33791AF", "G37399XV", "G38663NM", "G49108TO" ], "uniprot_id": "Q16620" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222178" }, { "confidence": "high", "disease": "Multidrug resistant cancer", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux of chemotherapeutic drugs, reducing intracellular drug concentration and promoting MDR phenotype.", "protein": "P-glycoprotein (P-gp/ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12222209" }, { "confidence": "high", "disease": "Acute lymphoblastic leukemia (ALL)", "glycan_involvement": "Glycosylation supports stability and trafficking.", "mechanism": "Upregulation confers resistance to multiple antineoplastic agents.", "protein": "MRP1 (ABCC1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12222209" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation at N596 critical for function.", "mechanism": "Efflux of chemotherapeutics, upregulated by hypoxia and c-Myc, leading to MDR.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "causal", "source_pmcid": "PMC12222209" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "Overexpression correlates with poor prognosis and chemoresistance; inhibition sensitizes cells to chemotherapy.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12222209" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "No direct glycan modification described, but glycoprotein nature supports stability.", "mechanism": "Overexpression promotes glycolysis, autophagy, and resistance to paclitaxel and tamoxifen.", "protein": "Hexokinase 2 (HK2)", "protein_enriched": { "function": "Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (PubMed:23185017, PubMed:26985301, Pub", "gene_name": "HK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P52789" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222209" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Secreted glycoprotein; glycosylation aids secretion.", "mechanism": "Acts as autocrine motility factor, activates HER2/PI3K/Akt signaling, conferring trastuzumab resistance.", "protein": "Phosphohexose isomerase (PGI/GPI)", "protein_enriched": { "function": "In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it'", "gene_name": "GPI", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92350NX", "G59324HL", "G66088HZ", "G49108TO" ], "uniprot_id": "P06744" }, "relationship_type": "causal", "source_pmcid": "PMC12222209" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "No direct glycan modification described.", "mechanism": "Phosphorylation and membrane translocation activate PI3K/Akt, promoting proliferation and drug resistance.", "protein": "Phosphofructokinase-1 (PFK1)", "relationship_type": "causal", "source_pmcid": "PMC12222209" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "No direct glycan modification described.", "mechanism": "Nuclear translocation promotes drug resistance and poor prognosis.", "protein": "Triosephosphate isomerase (TPI1)", "protein_enriched": { "function": "Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis a", "gene_name": "TPI1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G67350BD", "G79666IR" ], "uniprot_id": "P60174" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12222209" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Surface localization may involve glycosylation.", "mechanism": "Upregulation and membrane localization promote doxorubicin resistance and cell adhesion-mediated drug resistance.", "protein": "Enolase 1 (ENO1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222209" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "No direct glycan modification described.", "mechanism": "Nuclear PKM2 promotes DNA repair, gene expression, and resistance to gemcitabine.", "protein": "Pyruvate kinase M2 (PKM2)", "protein_enriched": { "function": "Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618-1" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12222209" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "VEGF promotes neurogenesis and angiogenesis, aiding recovery after stroke.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates VEGF bioactivity and distribution in neural tissue.", "mechanism": "VEGF supports neural stem cell proliferation and survival, potentially counteracting neurodegeneration.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222294" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Polysialylation (glycan modification) is essential for NCAM function in neurogenesis.", "mechanism": "PSA-NCAM marks immature neurons; reduced levels indicate impaired neurogenesis in Alzheimer's.", "protein": "PSA-NCAM", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "GFAP is glycosylated, affecting filament assembly and cell signaling.", "mechanism": "GFAP marks astrocytes and neural stem cells; elevated levels reflect gliosis and neuroinflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "MBP glycosylation influences myelin stability and immune recognition.", "mechanism": "MBP is a marker of myelinating oligodendrocytes; loss indicates demyelination in MS.", "protein": "MBP", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "DCX glycosylation may affect microtubule binding and neuron migration.", "mechanism": "DCX marks migrating immature neurons; increased expression indicates neurogenesis after injury.", "protein": "DCX", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Spinal cord injury", "glycan_involvement": "BLBP glycosylation modulates lipid binding and cell signaling.", "mechanism": "BLBP marks glial progenitors; upregulation reflects activation of repair mechanisms.", "protein": "BLBP", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "NeuN glycosylation may affect nuclear localization and function.", "mechanism": "NeuN marks mature neurons; loss correlates with neuronal degeneration in ALS.", "protein": "NeuN", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "GLAST glycosylation influences transporter activity and cell surface expression.", "mechanism": "GLAST marks astrocytic lineage; altered expression reflects glial dysfunction in PD.", "protein": "GLAST", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "O4 is a glycoprotein; glycan epitopes are critical for cell recognition and differentiation.", "mechanism": "O4 marks pre-oligodendrocytes; reduced levels indicate impaired remyelination in MS.", "protein": "O4", "relationship_type": "biomarker", "source_pmcid": "PMC12222294" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Heparan sulfate chains mediate exosome targeting and uptake.", "mechanism": "Exosomal GPC1+ levels are elevated in pancreatic cancer patients, enabling highly sensitive and specific detection.", "protein": "Glypican-1 (GPC1)", "protein_enriched": { "function": "Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a cataly", "gene_name": "GPC1", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G10486CT", "G27058EU", "G41071NU", "G42124LM", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G66621EA", "G72790NZ", "G80920RR", "G90659AW", "G91636VS", "G95865ZB", "G57321FI", "G43417UB", "G49108TO", "G83460ZZ" ], "uniprot_id": "P35052" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Heparan sulfate glycosylation affects exosome interaction.", "mechanism": "GPC1+ exosomes are increased in CRC patient plasma and tumor tissue, correlating with disease presence.", "protein": "Glypican-1 (GPC1)", "protein_enriched": { "function": "Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a cataly", "gene_name": "GPC1", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G10486CT", "G27058EU", "G41071NU", "G42124LM", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G66621EA", "G72790NZ", "G80920RR", "G90659AW", "G91636VS", "G95865ZB", "G57321FI", "G43417UB", "G49108TO", "G83460ZZ" ], "uniprot_id": "P35052" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation modulates EGFR stability and exosome sorting.", "mechanism": "Exosomal EGFR is highly expressed in NSCLC patient samples, distinguishing cancer from controls.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "N-glycosylation critical for CEA antigenicity and exosome incorporation.", "mechanism": "Exosomal CEA is elevated in CRC, supporting its use in diagnosis.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances immune checkpoint function.", "mechanism": "Exosomal PD-L1 correlates with disease progression, immune evasion, and poor prognosis.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "N-glycosylation required for HER2 dimerization and exosome packaging.", "mechanism": "Serum exosomal HER2 is a promising marker for advanced gastric cancer.", "protein": "HER2", "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation modulates Claudin 4 membrane localization.", "mechanism": "Exosomal Claudin 4 increases with ovarian cancer progression.", "protein": "Claudin 4", "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation affects fibronectin structure and exosome association.", "mechanism": "Exosomal fibronectin is highly diagnostic for breast cancer.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation regulates CD24 exosome sorting and immune interactions.", "mechanism": "Exosomal CD24 enables early detection of ovarian cancer.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Chondroitin sulfate glycosylation mediates versican's exosome function.", "mechanism": "Plasma exosomal versican is a potential diagnostic marker for NSCLC.", "protein": "Versican", "protein_enriched": { "function": "May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222296" }, { "confidence": "high", "disease": "Loeys-Dietz syndrome (LDS)", "glycan_involvement": "N-glycosylation required for proper folding and trafficking.", "mechanism": "Loss-of-function or dominant-negative mutations impair TGF\u03b2 signaling, leading to vascular and skeletal abnormalities.", "protein": "TGFBR1", "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Loeys-Dietz syndrome (LDS)", "glycan_involvement": "N-glycosylation critical for stability and cell surface expression.", "mechanism": "Missense mutations disrupt receptor function and signaling, causing connective tissue defects.", "protein": "TGFBR2", "protein_enriched": { "function": "Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transdu", "gene_name": "TGFBR2", "glycan_count": 12, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G13694XX", "G37881RL", "G38663NM", "G55412XP", "G56784JY", "G57888GL", "G62461SM", "G57321FI", "G11629QQ", "G22310AV", "G62765YT", "G80920RR" ], "uniprot_id": "P37173" }, "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Marfan syndrome type 2 (MFS2)", "glycan_involvement": "N-glycosylation affects receptor folding and trafficking.", "mechanism": "Mutations in STK domain reduce signaling, leading to MFS2 phenotype.", "protein": "TGFBR2", "protein_enriched": { "function": "Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transdu", "gene_name": "TGFBR2", "glycan_count": 12, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G13694XX", "G37881RL", "G38663NM", "G55412XP", "G56784JY", "G57888GL", "G62461SM", "G57321FI", "G11629QQ", "G22310AV", "G62765YT", "G80920RR" ], "uniprot_id": "P37173" }, "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Multiple self-healing squamous epithelioma (MSSE)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Loss-of-function mutations act as tumor suppressor; somatic loss leads to skin cancer.", "protein": "TGFBR1", "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Thoracic aortic aneurysms and dissections (TAAD)", "glycan_involvement": "N-glycosylation impacts receptor stability.", "mechanism": "Germline mutations impair signaling, predisposing to aortic disease.", "protein": "TGFBR2", "protein_enriched": { "function": "Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transdu", "gene_name": "TGFBR2", "glycan_count": 12, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G13694XX", "G37881RL", "G38663NM", "G55412XP", "G56784JY", "G57888GL", "G62461SM", "G57321FI", "G11629QQ", "G22310AV", "G62765YT", "G80920RR" ], "uniprot_id": "P37173" }, "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Vascular Ehlers-Danlos syndrome (vEDS)", "glycan_involvement": "Glycosylation affects collagen fibril stability.", "mechanism": "Mutations disrupt collagen III structure, causing vascular fragility.", "protein": "COL3A1", "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "medium", "disease": "Loeys-Dietz syndrome (LDS)", "glycan_involvement": "Potential O-glycosylation modulates activity.", "mechanism": "Mutations impair downstream TGF\u03b2 signaling, leading to LDS type 3.", "protein": "SMAD3", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P84022" }, "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "medium", "disease": "Loeys-Dietz syndrome (LDS)", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Mutations alter ligand function, contributing to LDS type 4.", "protein": "TGFB2", "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Hereditary hemorrhagic telangiectasia (HHT)", "glycan_involvement": "N-glycosylation essential for trafficking.", "mechanism": "Mutations cause misfolding and ER retention, impairing TGF\u03b2 signaling.", "protein": "Endoglin (ENG)", "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Familial pulmonary arterial hypertension", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "Mutations lead to misfolding and ERAD-mediated degradation.", "protein": "BMPR2", "protein_enriched": { "function": "On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autopho", "gene_name": "BMPR2", "glycan_count": 7, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G31852PQ", "G46503DX", "G70375MX", "G49108TO", "G10486CT", "G50045TK" ], "uniprot_id": "Q13873" }, "relationship_type": "causal", "source_pmcid": "PMC12222301" }, { "confidence": "high", "disease": "Cancer (Tumor Microenvironment)", "glycan_involvement": "N-glycosylation modulates ligand binding and macrophage polarization.", "mechanism": "Upregulated in M2-like macrophages, associated with protumor activity and immunosuppression.", "protein": "CD206 (MRC2)", "relationship_type": "biomarker", "source_pmcid": "PMC12222308" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects receptor function and scavenging activity.", "mechanism": "Expressed in M2-like macrophages, linked to anti-inflammatory response and plaque stability.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Cancer (Tumor Microenvironment)", "glycan_involvement": "N-glycosylation may regulate enzyme stability and activity.", "mechanism": "Promotes M2-like polarization, suppresses anti-tumor immunity.", "protein": "Arginase-1 (Arg-1)", "protein_enriched": { "function": "Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathway", "gene_name": "ARG1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05089" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Acute-on-Chronic Liver Failure (ACLF)", "glycan_involvement": "N-glycosylation modulates chemokine receptor signaling.", "mechanism": "Key enzyme in 5-ALA-induced M2 polarization, associated with improved outcomes.", "protein": "CX3CR1", "protein_enriched": { "function": "Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune respons", "gene_name": "CX3CR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49238" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Cancer (Tumor Microenvironment)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Production reduced by N-glycosylation inhibition, linked to M2-like macrophage recruitment.", "protein": "CCL22", "protein_enriched": { "function": "May play a role in the trafficking of activated/effector T-lymphocytes to inflammatory sites and other aspects of activated T-lymphocyte physiology. Chemotactic for monocytes, dendritic cells and natu", "gene_name": "CCL22", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00626" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222308" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "N-glycosylation essential for cytokine stability and secretion.", "mechanism": "Produced by M2-like macrophages, suppresses inflammation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Obesity/Metabolic Disease", "glycan_involvement": "N-glycosylation affects cytokine activity.", "mechanism": "Produced by M1-like macrophages, promotes insulin resistance.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Autoimmunity", "glycan_involvement": "N-glycosylation modulates receptor binding.", "mechanism": "Produced by M1-like macrophages, drives autoimmune inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation may affect enzyme localization.", "mechanism": "Upregulated in M1-like macrophages, contributes to plaque instability.", "protein": "iNOS (NOS2)", "relationship_type": "causal", "source_pmcid": "PMC12222308" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "N-glycosylation critical for pathogen binding.", "mechanism": "Upregulated in M2-like macrophages, involved in pathogen recognition.", "protein": "CD209 (DC-SIGN)", "relationship_type": "biomarker", "source_pmcid": "PMC12222308" }, { "confidence": "high", "disease": "Cholestatic liver injury", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated ALP indicates bile duct injury in C. psittaci pneumonia patients.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "high", "disease": "Cholestatic liver injury", "glycan_involvement": "GGT is a glycoprotein; glycosylation modulates its activity.", "mechanism": "Elevated GGT reflects bile duct damage in C. psittaci pneumonia.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "high", "disease": "Hepatocellular injury", "glycan_involvement": "Minor glycosylation; not primary to function.", "mechanism": "Elevated AST signals hepatocyte injury in C. psittaci pneumonia.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "high", "disease": "Hepatocellular injury", "glycan_involvement": "Minor glycosylation; not primary to function.", "mechanism": "ALT elevation marks hepatocyte damage in C. psittaci pneumonia.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects half-life.", "mechanism": "Decreased albumin correlates with severity of liver injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "CRP is a glycoprotein; glycosylation modulates immune recognition.", "mechanism": "CRP elevation reflects systemic inflammation and correlates with liver injury severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "PCT is glycosylated; glycosylation affects secretion.", "mechanism": "PCT elevation indicates systemic inflammation and is associated with liver injury.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects clearance.", "mechanism": "Elevated D-dimer correlates with severity of liver injury and systemic inflammation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Minor glycosylation; not primary to function.", "mechanism": "LDH elevation reflects tissue injury including liver in C. psittaci pneumonia.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "medium", "disease": "Mixed liver injury", "glycan_involvement": "Glycosylation modulates GGT activity and secretion.", "mechanism": "GGT elevation, with ALT/AST, indicates mixed hepatocellular and cholestatic injury.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12222624" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "CRP is heavily glycosylated, which affects its stability and function in inflammation.", "mechanism": "CRP levels increase in response to inflammatory stimuli, indicating systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "IL-6 glycosylation modulates its secretion and receptor binding.", "mechanism": "IL-6 is upregulated during inflammatory response, mediating acute-phase reactions.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects its stability and bioactivity.", "mechanism": "TNF-\u03b1 is a key cytokine driving inflammation and tissue damage.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Albumin glycosylation status can change in liver disease, affecting its half-life.", "mechanism": "Serum albumin decreases in liver dysfunction due to impaired synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "ALP is N-glycosylated, and glycan changes can affect its serum levels.", "mechanism": "ALP increases in liver dysfunction, reflecting cholestasis or hepatobiliary injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "Hepatobiliary dysfunction", "glycan_involvement": "GGT glycosylation is essential for its membrane localization and activity.", "mechanism": "GGT elevation indicates hepatobiliary injury or dysfunction.", "protein": "Gamma glutamyl transferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects enzyme stability and function.", "mechanism": "Impaired activity leads to defective bilirubin conjugation in liver disease.", "protein": "UDP-glucuronyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity in vascular disease.", "mechanism": "CRP is associated with increased risk and progression of atherosclerosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycosylation can enhance IL-6 signaling in cancer.", "mechanism": "Chronic elevation of IL-6 promotes tumorigenesis and cancer progression.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12223399" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation affects CRP's role in metabolic inflammation.", "mechanism": "Elevated CRP is linked to chronic inflammation in diabetes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12223399" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding affinity.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2, enabling viral infection.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect TMPRSS2 stability and localization.", "mechanism": "TMPRSS2 primes the SARS-CoV-2 spike protein for cell entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "high", "disease": "Fever", "glycan_involvement": "N-glycosylation required for IL-6 secretion and stability.", "mechanism": "IL-6 is a pyrogenic cytokine released during infection, inducing fever.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Fever", "glycan_involvement": "Glycosylation influences IL-1\u03b2 secretion.", "mechanism": "IL-1\u03b2 stimulates the hypothalamic temperature center, causing fever.", "protein": "Interleukin-1 beta", "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Fever", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding.", "mechanism": "TNF-\u03b1 acts as a pyrogen, promoting fever during infection.", "protein": "Tumor necrosis factor alpha", "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation modulates IL-6 bioactivity.", "mechanism": "Elevated IL-6 is a hallmark of cytokine storm in severe COVID-19.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation required for proper cytokine function.", "mechanism": "High IL-1\u03b2 levels contribute to hyperinflammation in COVID-19.", "protein": "Interleukin-1 beta", "relationship_type": "biomarker", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 signaling.", "mechanism": "TNF-\u03b1 elevation is associated with severe inflammatory response.", "protein": "Tumor necrosis factor alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Respiratory tract infections", "glycan_involvement": "N-glycosylation affects receptor-virus interaction.", "mechanism": "ACE2 is a receptor for multiple coronaviruses causing respiratory infections.", "protein": "Angiotensin-converting enzyme 2", "relationship_type": "causal", "source_pmcid": "PMC12223423" }, { "confidence": "medium", "disease": "Respiratory tract infections", "glycan_involvement": "N-glycosylation required for IL-6 function.", "mechanism": "IL-6 is elevated in various respiratory infections, indicating inflammation.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12223423" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "Envelope protein is glycosylated, facilitating viral entry and immune evasion; glycosylation is essential for G-Rb2 binding.", "mechanism": "Ginsenoside Rb2 binds directly to the ZIKV envelope glycoprotein, neutralizing viral infectivity.", "protein": "Zika virus envelope protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the host cell membrane and packages the viral RNA into a nucleocapsid that forms the core of the mature virus particle. During virus entry, may induce genom", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q32ZE1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223433" }, { "confidence": "high", "disease": "Microcephaly", "glycan_involvement": "Glycosylation of envelope protein is critical for neurotropism.", "mechanism": "ZIKV envelope glycoprotein mediates viral entry into neural progenitor cells, leading to fetal brain development defects.", "protein": "Zika virus envelope protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the host cell membrane and packages the viral RNA into a nucleocapsid that forms the core of the mature virus particle. During virus entry, may induce genom", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q32ZE1" }, "relationship_type": "causal", "source_pmcid": "PMC12223433" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 syndrome", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "ZIKV envelope glycoprotein triggers autoimmune responses post-infection.", "protein": "Zika virus envelope protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the host cell membrane and packages the viral RNA into a nucleocapsid that forms the core of the mature virus particle. During virus entry, may induce genom", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q32ZE1" }, "relationship_type": "causal", "source_pmcid": "PMC12223433" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Envelope glycoprotein glycosylation is required for viral infectivity and G-Rb2 interaction.", "mechanism": "Ginsenoside Rb2 shows antiviral activity against JEV by targeting its envelope glycoprotein.", "protein": "Japanese encephalitis virus envelope protein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle (By similarity). During virus entry, may in", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P06935" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223433" }, { "confidence": "medium", "disease": "viral infectious disease", "glycan_involvement": "Glycosylation of envelope protein facilitates G-Rb2 binding.", "mechanism": "Ginsenoside Rb2 inhibits Langat virus infectivity by binding to its envelope glycoprotein.", "protein": "Langat virus envelope protein", "protein_enriched": { "function": "Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the clearance of nucleic acids generated through apoptosis, hence preventing autoinflammation. N", "gene_name": "Dnase2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9QZK8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223433" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "Surface antigen glycosylation is essential for viral assembly and immune evasion.", "mechanism": "Ginsenosides (e.g., G-Rg3, G-Rh1) reduce HBV infectivity by modulating immune response and possibly interacting with surface glycoprotein.", "protein": "Hepatitis B virus surface antigen", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223433" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "E2 glycoprotein glycosylation is critical for viral entry and immune escape.", "mechanism": "Ginsenosides (e.g., G-Rg3, G-Rh1) decrease HCV infectivity by enhancing immune response and potentially interacting with E2 glycoprotein.", "protein": "Hepatitis C virus E2 glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223433" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune response.", "mechanism": "Spike protein mediates viral entry and immune activation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Contains glycosylation sites affecting antigenicity.", "mechanism": "Anti-NC antibodies indicate prior infection.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "CD4 is N-glycosylated, affecting cell-cell interactions and stability.", "mechanism": "CD4+ T cell percentage and CD4/CD8 ratio are markers of immune recovery and chronic inflammation.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "CD8 is N-glycosylated, influencing T cell receptor interactions.", "mechanism": "CD8+ T cell levels contribute to CD4/CD8 ratio, a marker of immune status.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation modulates receptor function and Treg stability.", "mechanism": "CD25+ Tregs suppress inflammation; depletion linked to chronic inflammation in long COVID.", "protein": "CD25 (IL2RA)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Not a glycoprotein; used as a marker for Treg identification.", "mechanism": "FOXP3+ Tregs maintain immune tolerance; reduction associated with increased inflammation.", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and function.", "mechanism": "CRP levels reflect systemic inflammation in COVID-19 and long COVID.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "Ratio reflects glycoprotein-modified T cell populations.", "mechanism": "Higher CD4/CD8 ratio after G1899 treatment indicates improved immune recovery and reduced chronic inflammation.", "protein": "CD4/CD8 ratio", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "Glycosylation of CD25 and CD4 supports Treg function.", "mechanism": "Maintenance of Treg population by G1899 is associated with attenuation of chronic inflammation.", "protein": "CD4+CD25+FOXP3+ Tregs", "relationship_type": "protective", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "Spike glycosylation affects antibody recognition and immune evasion.", "mechanism": "Anti-spike antibody levels used to monitor immune response post-infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12223517" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "IL-6 is glycosylated, affecting stability and receptor binding.", "mechanism": "IL-6 drives neuroinflammation, BBB leakage, and B cell infiltration in NMOSD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12223566" }, { "confidence": "high", "disease": "Aicardi-Gouti\u00e8res Syndrome (AGS)", "glycan_involvement": "IFN-\u03b1 glycosylation modulates secretion and activity.", "mechanism": "CNS-specific IFN-\u03b1 overproduction causes microangiopathy, calcification, and encephalopathy.", "protein": "Interferon-alpha (IFN-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12223566" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects IL-6 stability and signaling.", "mechanism": "Astrocyte-targeted IL-6 induces progressive neuroinflammation and motor decline.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12223566" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation influences IFN-\u03b1 receptor interaction.", "mechanism": "Subclinical IFN-\u03b1 amplifies IL-6-driven neuroinflammation, increasing immune cell infiltration.", "protein": "Interferon-alpha (IFN-\u03b1)", "relationship_type": "exacerbating", "source_pmcid": "PMC12223566" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "C3 glycosylation is essential for function and immune recognition.", "mechanism": "Upregulated in IL-6-driven CNS inflammation, marking acute-phase response.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223566" }, { "confidence": "medium", "disease": "Demyelination", "glycan_involvement": "MOG glycosylation affects antigenicity and immune response.", "mechanism": "MOG immunization in IL-6 transgenic mice shifts inflammation to brain, enhancing demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC12223566" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Potential glycosylation may affect STAT1 localization and function.", "mechanism": "STAT1 phosphorylation (especially S727) marks IFN-\u03b1/IL-6-induced CNS inflammation.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223566" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates chemokine gradient formation.", "mechanism": "CXCL10 upregulation correlates with T cell recruitment in CNS inflammation.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223566" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects chemokine-receptor interactions.", "mechanism": "CCL5 upregulation promotes immune cell infiltration in CNS.", "protein": "CCL5", "relationship_type": "biomarker", "source_pmcid": "PMC12223566" }, { "confidence": "low", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may regulate SOCS3 stability.", "mechanism": "SOCS3 upregulated by IL-6, modulates JAK/STAT signaling in CNS inflammation.", "protein": "SOCS3", "relationship_type": "regulatory", "source_pmcid": "PMC12223566" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "No direct glycosylation reported; function is epigenetic regulation.", "mechanism": "PALI1 suppresses oncogenic transcriptional programs and maintains heterochromatin stability; its downregulation by arsenic promotes carcinogenesis.", "protein": "PALI1", "relationship_type": "protective", "source_pmcid": "PMC12223765" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Higher PALI1 expression correlates with improved survival; arsenic-induced repression may drive tumor progression.", "protein": "PALI1", "relationship_type": "protective", "source_pmcid": "PMC12223765" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "PALI1 downregulation by arsenic disrupts chromatin repression, facilitating carcinogenesis.", "protein": "PALI1", "relationship_type": "protective", "source_pmcid": "PMC12223765" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "PALI1 may act as tumor suppressor or oncogene depending on context; arsenic represses PALI1, potentially promoting cancer.", "protein": "PALI1", "relationship_type": "context-dependent", "source_pmcid": "PMC12223765" }, { "confidence": "high", "disease": "Genomic instability", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "PALI1 loss leads to H3K9me3 depletion, derepression of LINE-1 retrotransposons, and genome instability.", "protein": "PALI1", "relationship_type": "causal", "source_pmcid": "PMC12223765" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "EZH2 catalyzes H3K27me3; its activity is maintained despite arsenic exposure, contributing to altered chromatin states.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223765" }, { "confidence": "high", "disease": "Genomic instability", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "G9a is recruited by PALI1 for H3K9me3 deposition; arsenic reduces G9a and PALI1, leading to heterochromatin loss.", "protein": "G9a (EHMT2)", "protein_enriched": { "function": "Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcripti", "gene_name": "EHMT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96KQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12223765" }, { "confidence": "high", "disease": "Genomic instability", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Loss of H3K9me3 silencing at LINE-1 loci activates retrotransposons, causing DNA damage and instability.", "protein": "LINE-1 ORF1p", "protein_enriched": { "function": "Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially m", "gene_name": "L1RE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UN81" }, "relationship_type": "causal", "source_pmcid": "PMC12223765" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "SUZ12 is a PRC2 core subunit; its reduction by arsenic may contribute to epigenetic dysregulation.", "protein": "SUZ12", "protein_enriched": { "function": "Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (", "gene_name": "SUZ12", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G10846ZT" ], "uniprot_id": "Q15022" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12223765" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "JARID2 is PRC2.2 accessory protein; its expression is altered by arsenic, affecting chromatin repression balance.", "protein": "JARID2", "protein_enriched": { "function": "Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis (PubMed:2007", "gene_name": "JARID2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92833" }, "relationship_type": "biomarker", "source_pmcid": "PMC12223765" }, { "confidence": "high", "disease": "Peritoneal Fibrosis (PF)", "glycan_involvement": "EGFR is N-glycosylated; glycosylation modulates receptor function and signaling", "mechanism": "PRMT1-mediated H4R3me2a enhances EGFR transcription and activation, driving downstream profibrotic signaling (STAT3, AKT, ERK, Snail)", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12223772" }, { "confidence": "high", "disease": "Peritoneal Fibrosis (PF)", "glycan_involvement": "CA125 is a heavily glycosylated mucin; glycosylation critical for its secretion and detection", "mechanism": "CA125 levels in dialysis effluent inversely correlate with PF severity and PRMT1 expression; reflects mesothelial cell mass", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12223772" }, { "confidence": "high", "disease": "Peritoneal Fibrosis (PF)", "glycan_involvement": "Collagen I is glycosylated, affecting fibril formation and ECM deposition", "mechanism": "Collagen I deposition is a hallmark of PF; upregulated by PRMT1/EGFR axis", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "causal", "source_pmcid": "PMC12223772" }, { "confidence": "medium", "disease": "Peritoneal Fibrosis (PF)", "glycan_involvement": "Fibronectin glycosylation modulates cell adhesion and ECM assembly", "mechanism": "Fibronectin upregulated during PF and EMT; suppressed by PRMT1 inhibition", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", 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"G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12223772" }, { "confidence": "medium", "disease": "Triple Negative Breast Cancer", "glycan_involvement": "EGFR glycosylation modulates receptor function in cancer", "mechanism": "PRMT1 regulates EGFR activity, promoting malignant transitions", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12223772" }, { "confidence": "medium", "disease": "Peritoneal Fibrosis (PF)", "glycan_involvement": "E-Cadherin glycosylation affects cell-cell adhesion and EMT", "mechanism": "E-Cadherin loss is associated with EMT and PF progression; PRMT1 inhibition restores E-Cadherin", "protein": "E-Cadherin", "relationship_type": "protective", "source_pmcid": "PMC12223772" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "PD-L1 glycosylation stabilizes the protein and enhances its immune inhibitory function.", "mechanism": "PD-L1 is overexpressed in NSCLC tumor cells, mediating immune evasion by inhibiting T cell activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Indirect; ER\u03b1 signaling may influence PD-L1 glycosylation and expression.", "mechanism": "ER\u03b1 expression is strongly associated with PD-L1 positivity in NSCLC, suggesting ER\u03b1 promotes immune escape via upregulation of PD-L1.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Immune Evasion in NSCLC", "glycan_involvement": "Indirect; ER\u03b1-driven PD-L1 upregulation increases glycosylated PD-L1 at the cell surface.", "mechanism": "ER\u03b1 promotes tumor immune evasion by upregulating PD-L1, especially in premenopausal women.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "causal", "source_pmcid": "PMC12224011" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "None direct; ER\u03b2 does not regulate PD-L1 glycosylation.", "mechanism": "ER\u03b2 is the predominant estrogen receptor in PD-L1-negative NSCLC, associated with cell proliferation and tumor growth.", "protein": "Estrogen Receptor beta (ER\u03b2)", "protein_enriched": { "function": "Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-depen", "gene_name": "ESR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q92731" }, "relationship_type": "causal", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "None", "mechanism": "AR expression is low and not associated with PD-L1 status or immune evasion in NSCLC.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "neutral", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Immune Evasion in NSCLC", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances its immune inhibitory function.", "mechanism": "Glycosylated PD-L1 on tumor cells inhibits T cell activation, facilitating immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Indirect; reducing ER\u03b1 signaling may decrease PD-L1 glycosylation and surface expression.", "mechanism": "Antiestrogen therapy targeting ER\u03b1 may enhance immunotherapy efficacy in PD-L1+ NSCLC patients.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "N-glycosylation is required for PD-L1 stability and detection.", "mechanism": "PD-L1 expression is used to stratify NSCLC patients for immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Indirect; ER\u03b1 status may predict PD-L1 glycosylation-dependent immune evasion.", "mechanism": "ER\u03b1 expression identifies NSCLC patients with higher likelihood of PD-L1 positivity and potential benefit from combined antiestrogen and immunotherapy.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Indirect; increased ER\u03b1 may drive higher PD-L1 glycosylation and immune escape.", "mechanism": "Higher ER\u03b1 expression in premenopausal women correlates with increased PD-L1-mediated immune evasion.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "causal", "source_pmcid": "PMC12224011" }, { "confidence": "high", "disease": "Plant viral infection", "glycan_involvement": "PLCPs are glycoproteins; glycosylation may affect stability and activity during stress.", "mechanism": "NbXCP1 expression increases during viral infection, suggesting involvement in immune response and protein degradation.", "protein": "NbXCP1", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "high", "disease": "Plant viral infection", "glycan_involvement": "Likely N-glycosylated, impacting folding and function.", "mechanism": "NbXCP2 is upregulated during viral infection, indicating a role in defense and protein turnover.", "protein": "NbXCP2", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "high", "disease": "Plant viral infection", "glycan_involvement": "Glycosylation may regulate protease activity.", "mechanism": "NbXCP3 shows increased expression post-infection, contributing to immune response.", "protein": "NbXCP3", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Verticillium wilt (Verticillium dahliae infection)", "glycan_involvement": "Glycosylation may affect secretion and stability.", "mechanism": "Orthologous gene in cotton enhances resistance to Verticillium dahliae; NbRD21D likely confers disease resistance.", "protein": "NbRD21D", "relationship_type": "protective", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Plant viral infection", "glycan_involvement": "Glycosylation may modulate activity during stress.", "mechanism": "NbCEP1 is rapidly activated during early infection, suggesting a role in acute defense response.", "protein": "NbCEP1", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Plant viral infection", "glycan_involvement": "Likely N-glycosylated, affecting function.", "mechanism": "NbTHI2 is rapidly activated in early infection, indicating involvement in defense signaling.", "protein": "NbTHI2", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Senescence", "glycan_involvement": "Glycosylation may regulate stability during aging.", "mechanism": "NbSAG12B is enriched on drought and high temperature elements, marking senescence and stress response.", "protein": "NbSAG12B", "relationship_type": "biomarker", "source_pmcid": "PMC12224012" }, { "confidence": "high", "disease": "Protein degradation in bioreactor", "glycan_involvement": "Inhibition of glycosylated PLCPs prevents degradation of glycoprotein therapeutics.", "mechanism": "SICYS8 inhibits PLCPs, enhancing recombinant protein (GFP) yield in N. benthamiana.", "protein": "SICYS8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Plant viral infection", "glycan_involvement": "Glycosylation may affect immune function.", "mechanism": "NbALP2 maintains high expression during infection, suggesting a broad regulatory role in immunity.", "protein": "NbALP2", "relationship_type": "causal", "source_pmcid": "PMC12224012" }, { "confidence": "medium", "disease": "Drought stress", "glycan_involvement": "Glycosylation may modulate stress response.", "mechanism": "NbRD19 subfamily members are early-response markers for dehydration stress, enhancing stress resistance.", "protein": "NbRD19", "relationship_type": "protective", "source_pmcid": "PMC12224012" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Not directly discussed; glycosylation status not specified.", "mechanism": "GLDH is released from damaged hepatocyte mitochondria, reflecting liver-specific injury.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Acute viral hepatitis", "glycan_involvement": "Not discussed.", "mechanism": "GLDH levels are much lower in viral hepatitis than DILI, aiding differential diagnosis.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Hepatocellular injury (DILI subtype)", "glycan_involvement": "Not discussed.", "mechanism": "GLDH levels are highest in hepatocellular DILI, correlating with severity.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Cholestatic injury (DILI subtype)", "glycan_involvement": "Not discussed.", "mechanism": "GLDH levels are lower in cholestatic DILI, helping to distinguish injury patterns.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Mixed liver injury (DILI subtype)", "glycan_involvement": "Not discussed.", "mechanism": "GLDH levels are intermediate in mixed DILI, supporting pattern classification.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Fulminant liver failure", "glycan_involvement": "Not discussed.", "mechanism": "Higher GLDH levels predict poor outcome and mortality in DILI patients.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Not discussed.", "mechanism": "GLDH has a short half-life, allowing real-time monitoring of liver injury progression.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "real-time biomarker", "source_pmcid": "PMC12224239" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Elevated \u03b22 glycoprotein I antibody levels are associated with SLE and disease activity.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates CD4 surface expression and function.", "mechanism": "Reduced CD4+ T cell numbers and altered metabolism correlate with SLE activity.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated IL-6 levels in plasma and supernatant correlate with SLE activity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects cytokine function.", "mechanism": "IL-10 levels positively correlate with SLEDAI-2K and metabolic activity.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-17 production increased by metabolic reprogramming, promoting inflammation.", "protein": "Interleukin-17 (IL-17)", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:18025225, PubMed:19144317, PubMed:26431948). Signals via IL17R", "gene_name": "Il17a", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q62386" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects receptor binding.", "mechanism": "TNF-\u03b1 levels correlate with SLE activity and CD4+ T cell metabolism.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IFN-\u03b3 levels correlate with SLEDAI-2K and metabolic activity.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-4 levels negatively correlate with SLE activity; anti-inflammatory role.", "protein": "Interleukin-4 (IL-4)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated LDH reflects increased glycolysis and correlates with SLE activity.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antibody effector function.", "mechanism": "Presence of anti-dsDNA antibodies is diagnostic and correlates with disease activity.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12224248" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "GGT is a glycoprotein; glycosylation is required for its stability and function in serum.", "mechanism": "Elevated GGT reflects increased oxidative stress and inflammation, contributing to endothelial dysfunction and vascular damage, increasing stroke risk.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation supports GGT secretion and activity.", "mechanism": "High GGT is associated with increased risk of cardiovascular events via oxidative stress and metabolic dysfunction.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects GGT serum levels.", "mechanism": "GGT elevation is linked to metabolic syndrome components (obesity, dyslipidemia, insulin resistance).", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation required for GGT function.", "mechanism": "GGT is elevated in diabetes, reflecting oxidative stress and metabolic dysfunction.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation supports GGT's extracellular activity.", "mechanism": "GGT promotes oxidative modification of LDL, contributing to plaque formation.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "causal", "source_pmcid": "PMC12224381" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation affects GGT secretion.", "mechanism": "Obesity is associated with higher GGT, reflecting metabolic stress.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation required for GGT's serum stability.", "mechanism": "Nonlinear, positive association: stroke risk rises with GGT (especially 21\u201335 U/L), more pronounced in women, <60 years, non-diabetics, non-smokers.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation supports GGT's function as a serum biomarker.", "mechanism": "GGT is a stronger predictor of stroke in women than men, possibly due to lower baseline GGT and threshold effects.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation required for GGT's activity.", "mechanism": "GGT predicts stroke risk independently of alcohol use and diabetes.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation supports GGT's extracellular presence.", "mechanism": "Elevated GGT is associated with increased inflammation (e.g., CRP), linking to stroke via vascular injury.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12224381" }, { "confidence": "high", "disease": "Polycystic ovary syndrome", "glycan_involvement": "N-glycosylation affects SHBG stability and function.", "mechanism": "SHBG levels are altered in PCOS and reflect androgen status.", "protein": "Sex hormone-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "high", "disease": "Polycystic ovary syndrome", "glycan_involvement": "FSH is heavily N-glycosylated, affecting receptor binding.", "mechanism": "FSH levels are dysregulated in PCOS; chromium supplementation increases FSH.", "protein": "Follicle-stimulating hormone", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "high", "disease": "Polycystic ovary syndrome", "glycan_involvement": "LH is N-glycosylated, modulating bioactivity.", "mechanism": "LH/FSH ratio is elevated in PCOS; Ca+vitD+vitK reduces LH.", "protein": "Luteinizing hormone", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Apolipoproteins in VLDL are glycosylated, influencing lipid transport.", "mechanism": "VLDL levels are increased in PCOS; chromium reduces VLDL.", "protein": "Very low-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Apolipoprotein B glycosylation affects LDL metabolism.", "mechanism": "LDL-C is elevated in PCOS; curcumin and CoQ10 reduce LDL-C.", "protein": "Low-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Apolipoprotein A-I glycosylation modulates HDL function.", "mechanism": "HDL-C is reduced in PCOS; curcumin increases HDL-C.", "protein": "High-density lipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "N-glycosylation is essential for CRP secretion and function.", "mechanism": "hs-CRP is an inflammatory marker elevated in PCOS; omega-3 may reduce hs-CRP.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Minor glycosylation affects insulin clearance.", "mechanism": "Insulin resistance is common in PCOS; omega-3 and chromium improve HOMA-IR.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Glycosylation modulates enzyme stability.", "mechanism": "Soy isoflavones increase GSH and antioxidant capacity in PCOS.", "protein": "Glutathione peroxidase", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such ", "gene_name": "GPX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07203" }, "relationship_type": "protective", "source_pmcid": "PMC12224500" }, { "confidence": "low", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Carrier proteins for DHEAS are glycosylated.", "mechanism": "DHEAS levels are altered in PCOS; inositol may improve DHEAS.", "protein": "Dehydroepiandrosterone sulfate", "relationship_type": "biomarker", "source_pmcid": "PMC12224500" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Esterified vitamin A may interact with glycoprotein-rich joint matrix, but direct glycosylation not described.", "mechanism": "Higher serum levels associated with reduced all-cause and cancer mortality in OA patients; may modulate inflammation and oxidative stress.", "protein": "Retinyl palmitate", "relationship_type": "protective", "source_pmcid": "PMC12224656" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Similar to retinyl palmitate; indirect effects on glycoprotein matrix.", "mechanism": "Higher serum levels associated with reduced all-cause and cancer mortality in OA patients; possible anti-inflammatory effects.", "protein": "Retinyl stearate", "relationship_type": "protective", "source_pmcid": "PMC12224656" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation modulates binding affinity and serum half-life.", "mechanism": "Vitamin D binding protein transports vitamin D; higher vitamin D levels linked to reduced mortality in OA.", "protein": "Vitamin D binding protein", "relationship_type": "protective", "source_pmcid": "PMC12224656" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation required for proper membrane localization.", "mechanism": "Serum vitamin C shows U-shaped association with cardiovascular mortality in OA; transporter glycosylation affects vitamin C uptake.", "protein": "Vitamin C transporter (SVCT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12224656" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Highly glycosylated; glycosaminoglycan chains critical for cartilage function.", "mechanism": "Aggrecan degradation is central to OA pathology; vitamin D and retinyl esters may protect matrix integrity.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "causal", "source_pmcid": "PMC12224656" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Hydroxylysine glycosylation affects fibril stability.", "mechanism": "Collagen II breakdown drives cartilage loss in OA; micronutrients may support collagen synthesis.", "protein": "Collagen type II", "relationship_type": "causal", "source_pmcid": "PMC12224656" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "O-glycosylation modulates secretion and activity.", "mechanism": "Bone turnover marker; vitamin D regulates osteocalcin expression.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224656" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation affects secretion.", "mechanism": "COMP levels reflect cartilage turnover; may be influenced by micronutrient status.", "protein": "Cartilage oligomeric matrix protein (COMP)", "relationship_type": "biomarker", "source_pmcid": "PMC12224656" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "MMP-3 degrades cartilage matrix; retinyl esters may suppress MMP activity.", "protein": "Matrix metalloproteinase-3 (MMP-3)", "relationship_type": "causal", "source_pmcid": "PMC12224656" }, { "confidence": "low", "disease": "Osteoarthritis", "glycan_involvement": "Extensive O-glycosylation essential for lubricating function.", "mechanism": "Lubricin protects cartilage surfaces; micronutrients may support glycoprotein synthesis.", "protein": "Lubricin (PRG4)", "relationship_type": "protective", "source_pmcid": "PMC12224656" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not directly discussed; PLK1 is a kinase, but may be glycosylated as a regulatory mechanism.", "mechanism": "PLK1 is highly expressed in pancreatic cancer tissues and correlates with poor prognosis.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Gemcitabine-resistant pancreatic cancer", "glycan_involvement": "Not directly discussed; possible regulatory glycosylation not addressed.", "mechanism": "PLK1 is upregulated in gemcitabine-resistant cells; inhibition by MLN0905 restores drug sensitivity and induces apoptosis.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 promotes cell cycle progression, mitosis, and DNA replication, driving tumorigenesis.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "causal", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Gemcitabine-resistant pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 expression level positively correlates with resistance to gemcitabine.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "causal", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 inhibition (by MLN0905) induces cell cycle arrest and apoptosis in pancreatic cancer cells.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 phosphorylation (pPLK1) is elevated in pancreatic cancer and gemcitabine-resistant cells.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "biomarker", "source_pmcid": "PMC12224844" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 inhibition blocks angiogenesis in tumor xenografts (decreased CD31 expression).", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 inhibition reduces proliferation marker Ki67 in tumor tissue.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 inhibition increases DNA damage markers (PHH3, \u03b3H2A.x), leading to apoptosis.", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not discussed.", "mechanism": "PLK1 inhibition by MLN0905 is safe in vivo (no liver/kidney toxicity in mice).", "protein": "PLK1", "protein_enriched": { "function": "Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of c", "gene_name": "PLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P53350" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12224844" }, { "confidence": "high", "disease": "Carotid atherosclerosis", "glycan_involvement": "Glycosylation affects ALB stability and anti-inflammatory properties.", "mechanism": "Low ALB levels are associated with increased risk and early vascular damage in LADA patients.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12225120" }, { "confidence": "high", "disease": "Carotid atherosclerosis", "glycan_involvement": "Glycosylation modulates HDL function and anti-atherogenic properties.", "mechanism": "Low HDL-C levels increase risk of atherosclerosis; HDL particles contain glycoproteins involved in cholesterol transport.", "protein": "HDL-C", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Carotid atherosclerosis", "glycan_involvement": "ALT is glycosylated, affecting its secretion and stability.", "mechanism": "Elevated ALT reflects hepatic metabolic dysfunction and is linked to increased atherosclerosis risk in LADA.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "CRP glycosylation modulates its inflammatory activity.", "mechanism": "Elevated CRP correlates with increased cardiovascular risk and inflammation in LADA.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Carotid atherosclerosis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding and signaling.", "mechanism": "Elevated TNF-\u03b1 promotes inflammation and endothelial dysfunction, accelerating atherosclerosis in LADA.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Carotid atherosclerosis", "glycan_involvement": "Glycosylation regulates adiponectin multimerization and vascular protective effects.", "mechanism": "Abnormal adiponectin levels in LADA are linked to insulin resistance and atherosclerosis risk.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Carotid atherosclerosis", "glycan_involvement": "Glycosylation modulates leptin receptor interactions.", "mechanism": "Abnormal leptin levels contribute to metabolic dysfunction and atherosclerosis in LADA.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12225120" }, { "confidence": "high", "disease": "Latent autoimmune diabetes in adults (LADA)", "glycan_involvement": "Autoantibody glycosylation affects immune recognition and pathogenicity.", "mechanism": "Presence of autoantibodies distinguishes LADA and is linked to autoimmune beta-cell destruction.", "protein": "IAA/ICA/GADA", "relationship_type": "biomarker", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences ALB antioxidant capacity.", "mechanism": "Higher ALB levels are protective against cardiovascular complications in diabetes.", "protein": "Albumin (ALB)", "relationship_type": "protective", "source_pmcid": "PMC12225120" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation of HDL-associated proteins (e.g., ApoA-I) modulates anti-inflammatory effects.", "mechanism": "HDL-C reduces cardiovascular risk via reverse cholesterol transport; glycoproteins in HDL are essential for function.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12225120" }, { "confidence": "high", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation affects IFN-\u03b3 stability and secretion.", "mechanism": "Used as a diagnostic marker for LTBI via QuantiFERON-TB Gold Plus test.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "ESAT-6 triggers NLRP3 inflammasome activation, leading to cytokine release in LTBI.", "protein": "ESAT-6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A564" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation may regulate inflammasome assembly.", "mechanism": "Activation by ESAT-6 leads to macrophage death and cytokine maturation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Maturation and secretion promoted by NLRP3 activation in LTBI.", "protein": "Interleukin 1 beta (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "Secreted upon NLRP3 activation, contributing to immune response in LTBI.", "protein": "Interleukin 18 (IL-18)", "relationship_type": "causal", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "N-glycosylation critical for CD4 function and T cell activation.", "mechanism": "Caffeine increases CD4+ T cell frequency, enhancing immune response to Mtb.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation required for surface expression.", "mechanism": "Caffeine increases CD69+ expression, indicating T cell activation in LTBI.", "protein": "CD69", "protein_enriched": { "function": "Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells ", "gene_name": "CD69", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q07108" }, "relationship_type": "protective", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation affects receptor trafficking and function.", "mechanism": "Caffeine antagonizes A2A receptor, modulating immune response in LTBI.", "protein": "Adenosine A2A receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225470" }, { "confidence": "medium", "disease": "Latent tuberculosis infection (LTBI)", "glycan_involvement": "Glycosylation modulates secretion and receptor interaction.", "mechanism": "Caffeine and its metabolites inhibit TNF-\u03b1, reducing inflammation in LTBI.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12225470" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Non-enzymatic glycation (not classical glycosylation) reflects glucose exposure.", "mechanism": "HbA1c is used to diagnose diabetes, a risk factor for LTBI.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12225470" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Secreted as a glycoprotein; glycosylation required for stability and secretion", "mechanism": "Promotes tumor progression via STAT3 activation, correlates with advanced stage and grade", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12225652" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect stability and anti-apoptotic function", "mechanism": "Anti-apoptotic protein upregulated via IL-6/STAT3 axis; associated with advanced stage, lymph node involvement", "protein": "MCL-1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Secreted as a glycoprotein; glycosylation modulates chemokine activity", "mechanism": "Elevated in TNBC; promotes tumor-associated inflammation and immune cell recruitment", "protein": "MCP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate nuclear localization and stability", "mechanism": "Upregulated in high-grade tumors; downstream of IL-6/STAT3, involved in immune differentiation", "protein": "BCL-6", "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Secreted as a glycoprotein; glycosylation required for secretion", "mechanism": "Upregulated in tumor tissue; associated with advanced stage and grade, activates STAT3 pathway", "protein": "IL-23", "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation required for secretion and function", "mechanism": "Highly expressed in TNBC; drives aggressive phenotype via STAT3", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation may affect protein stability", "mechanism": "Overexpressed in TNBC; linked to apoptosis resistance", "protein": "MCL-1", "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Luminal breast cancer", "glycan_involvement": "Secreted as a glycoprotein; glycosylation modulates activity", "mechanism": "Elevated in luminal subtypes; promotes immune suppression via Treg recruitment", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for secretion and activity", "mechanism": "Elevated in plasma; reflects pro-inflammatory tumor microenvironment", "protein": "G-CSF", "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Secreted as a glycoprotein; glycosylation affects secretion", "mechanism": "Elevated in plasma; associated with advanced stage and grade", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225652" }, { "confidence": "high", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Defensins are glycoproteins; glycosylation may affect stability and secretion.", "mechanism": "Inhibits DENV replication and infectious particle production in skin cells; produced in response to infection.", "protein": "HBD-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "high", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "LL-37 is a glycoprotein; glycosylation may modulate peptide activity.", "mechanism": "Directly interacts with DENV E protein, inhibits viral entry and replication.", "protein": "LL-37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "high", "disease": "Zika virus infection (ZIKV)", "glycan_involvement": "Glycosylation may affect peptide stability and delivery via exosomes.", "mechanism": "Inhibits ZIKV replication in macrophages and reduces viral dissemination to placenta and testes.", "protein": "LL-37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Zika virus infection (ZIKV)", "glycan_involvement": "Contains WAP domain; glycosylation may influence nuclear translocation and function.", "mechanism": "Reduces ZIKV replication and infectious particle release in keratinocytes; immunoregulatory effect.", "protein": "Trappin-2/Elafin (Tr2/E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Glycosylation may affect peptide stability and immunomodulatory properties.", "mechanism": "Proposed to reduce systemic viral dissemination and modulate inflammation.", "protein": "Trappin-2/Elafin (Tr2/E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Zika virus infection (ZIKV)", "glycan_involvement": "Defensin glycosylation may affect exosome loading and function.", "mechanism": "Exosome-mediated delivery inhibits ZIKV replication in recipient cells.", "protein": "DEFA1B (\u03b1-defensin 1B)", "relationship_type": "protective", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Dengue virus infection (DENV)", "glycan_involvement": "Glycosylation may affect secretion and antiviral activity.", "mechanism": "Produced by keratinocytes in response to DENV; inhibits viral replication.", "protein": "HBD-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "West Nile virus infection (WNV)", "glycan_involvement": "Glycosylation may modulate peptide-virus interaction.", "mechanism": "Inhibits WNV replication in keratinocytes via direct interaction.", "protein": "LL-37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Placental damage (ZIKV/DENV)", "glycan_involvement": "Glycosylation may affect placental localization and function.", "mechanism": "Highly expressed in trophoblasts; proposed to protect against placental inflammation and viral dissemination.", "protein": "Trappin-2/Elafin (Tr2/E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "medium", "disease": "Testicular damage/infertility (ZIKV)", "glycan_involvement": "Glycosylation may affect exosome packaging and tissue targeting.", "mechanism": "Exosome-loaded LL-37 reduces testicular damage and improves sperm health in ZIKV-infected models.", "protein": "LL-37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225737" }, { "confidence": "high", "disease": "Diabetes-associated cognitive dysfunction", "glycan_involvement": "GLP-1R is a glycoprotein; glycosylation may affect receptor stability and signaling.", "mechanism": "Semaglutide (GLP-1RA) activation improves cognitive function via neuroprotection, reducing oxidative stress and inflammation.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Diabetes-associated cognitive dysfunction", "glycan_involvement": "LRP1 is highly N-glycosylated, which is critical for its trafficking and function.", "mechanism": "LRP1 expression is reduced in T2DM; semaglutide restores LRP1, preserving neuronal integrity and reducing apoptosis.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated, which may affect secretion and stability.", "mechanism": "Elevated in T2DM; semaglutide reduces IL-1\u03b2, indicating decreased neuroinflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "IL-6 glycosylation is important for secretion and receptor interaction.", "mechanism": "Increased in T2DM; semaglutide lowers IL-6, reflecting anti-inflammatory effects.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated, influencing its bioactivity.", "mechanism": "Elevated in T2DM; semaglutide reduces TNF-\u03b1, contributing to reduced inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "CRP is N-glycosylated, affecting its function in inflammation.", "mechanism": "CRP is increased in T2DM; semaglutide reduces CRP, indicating systemic and neuroinflammation reduction.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Neuronal apoptosis", "glycan_involvement": "N-glycosylation of LRP1 is essential for anti-apoptotic signaling.", "mechanism": "Reduced LRP1 in T2DM is associated with increased apoptosis; semaglutide restores LRP1 and reduces apoptosis.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates GLP-1R cell surface expression.", "mechanism": "GLP-1R agonists improve glycemic control and may protect against diabetes complications.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225814" }, { "confidence": "medium", "disease": "Diabetes-associated cognitive dysfunction", "glycan_involvement": "Potential O-glycosylation may affect nuclear localization.", "mechanism": "NeuN used as a neuronal marker; loss indicates neuronal damage in T2DM, improved with semaglutide.", "protein": "NeuN (RBFOX3)", "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Diabetes-associated cognitive dysfunction", "glycan_involvement": "N-glycosylation required for LRP1 function in the CNS.", "mechanism": "LRP1 downregulation correlates with cognitive impairment; restoration by semaglutide is neuroprotective.", "protein": "LRP1", "relationship_type": "biomarker", "source_pmcid": "PMC12225814" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation required for exosome formation and function.", "mechanism": "Exosomal marker used to identify hucMSC-EVs, which have therapeutic effects in T2DM.", "protein": "TSG101", "protein_enriched": { "function": "Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicu", "gene_name": "TSG101", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99816" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates exosome targeting and uptake.", "mechanism": "Exosomal marker; hucMSC-EVs containing CD9 improve insulin sensitivity and reduce oxidative damage.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects exosome-cell interactions.", "mechanism": "Exosomal marker; hucMSC-EVs containing CD81 mediate protective effects in T2DM.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Oxidative Damage", "glycan_involvement": "Glycosylation may regulate Nrf2 stability and activity.", "mechanism": "Upregulated by hucMSC-EVs, Nrf2 increases antioxidant enzyme expression, reducing ROS and oxidative damage.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Oxidative Damage", "glycan_involvement": "Glycosylation influences SOD1 secretion and activity.", "mechanism": "hucMSC-EVs upregulate SOD1, enhancing ROS clearance and protecting \u03b2 cells.", "protein": "SOD1", "relationship_type": "protective", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Cell Apoptosis", "glycan_involvement": "Glycosylation modulates Bcl2 anti-apoptotic function.", "mechanism": "hucMSC-EVs increase Bcl2 expression, inhibiting apoptosis in \u03b2 cells under oxidative stress.", "protein": "Bcl2", "protein_enriched": { "function": "Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondria", "gene_name": "BCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10415" }, "relationship_type": "protective", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation may affect DAPK1 localization and activity.", "mechanism": "DAPK1 promotes oxidative damage and apoptosis; targeted by miR-191-5p from hucMSC-EVs to alleviate T2DM pathology.", "protein": "DAPK1", "protein_enriched": { "function": "Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation duri", "gene_name": "SIK3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y2K2" }, "relationship_type": "causal", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation regulates PI3K receptor interactions.", "mechanism": "hucMSC-EVs activate PI3K/AKT pathway, improving insulin signaling and reducing IR.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation modulates AKT activation and downstream signaling.", "mechanism": "Activation by hucMSC-EVs restores glucose metabolism and antioxidant defense in T2DM.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225837" }, { "confidence": "medium", "disease": "Pancreatic \u03b2 Cell Dysfunction", "glycan_involvement": "Glycosylation influences STAT dimerization and nuclear translocation.", "mechanism": "hucMSC-EVs reactivate STAT signaling, supporting \u03b2 cell function and insulin secretion.", "protein": "STAT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12225837" }, { "confidence": "high", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "SAA4 detected in multiple glycosylated isoforms in patients; glycosylation may affect function and HDL association.", "mechanism": "Elevated SAA in HDL and LDL displaces ApoA-I, impairs anti-inflammatory HDL function, promotes inflammation.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "high", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "Glycosylation status not specified but ApoA-I is a glycoprotein; altered glycosylation may affect function.", "mechanism": "Downregulated in patient HDL/LDL; loss reduces anti-inflammatory and immunomodulatory protection.", "protein": "Apolipoprotein A-I (ApoA-I)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of SAA4 isoforms may modulate inflammatory activity.", "mechanism": "Elevated SAA promotes inflammation and is implicated in atherosclerosis pathogenesis.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation of SAA4 isoforms may influence tissue distribution and function.", "mechanism": "Elevated SAA correlates with disease severity and inflammation.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation may affect SAA clearance and proinflammatory activity.", "mechanism": "Elevated SAA associated with systemic inflammation in diabetes.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Crohn disease", "glycan_involvement": "Glycosylation may modulate SAA's immune interactions.", "mechanism": "Elevated SAA correlates with inflammatory activity in Crohn disease.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "Lysozyme C is a glycoprotein; glycosylation may affect stability and receptor interactions.", "mechanism": "Upregulated in patient LDL; may act on neuronal TLR4 to promote hyperexcitability and pain.", "protein": "Lysozyme C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "ApoA-II is a glycoprotein; glycosylation may influence lipid binding.", "mechanism": "Downregulated in patient HDL; loss may reduce anti-inflammatory capacity.", "protein": "Apolipoprotein A-II (ApoA-II)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "ApoC-III is O-glycosylated; glycan status may affect function.", "mechanism": "Downregulated in patient HDL/LDL; may contribute to altered lipid metabolism and inflammation.", "protein": "Apolipoprotein C-III (ApoC-III)", "protein_enriched": { "function": "Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin", "gene_name": "SERPINF2", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G06247RL", "G47518TP", "G48414YA", "G29068FM", "G43417UB", "G53434XO", "G49108TO" ], "uniprot_id": "P08697" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12226002" }, { "confidence": "medium", "disease": "Chronic peripheral neuropathic pain (NeuP)", "glycan_involvement": "Glycosylation status (isoforms) increased in patients; may affect HDL association and immune function.", "mechanism": "Multiple glycosylated isoforms detected in patient HDL; may reflect altered acute-phase response.", "protein": "Serum amyloid A4 (SAA4)", "protein_enriched": { "function": "Major acute phase reactant", "gene_name": "SAA4", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G06356OH", "G59626AS", "G82463GQ" ], "uniprot_id": "P35542" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226002" }, { "confidence": "high", "disease": "Peri-implantitis", "glycan_involvement": "OPG is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "Lower OPG levels are found in peri-implantitis sites compared to healthy peri-implant tissues, reflecting increased osteoclastic activity and bone resorption.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12226070" }, { "confidence": "high", "disease": "Bone resorption", "glycan_involvement": "Glycosylation is essential for OPG's function as a decoy receptor.", "mechanism": "OPG inhibits RANKL-RANK interaction, suppressing osteoclast differentiation and reducing bone resorption.", "protein": "Osteoprotegerin", "relationship_type": "protective", "source_pmcid": "PMC12226070" }, { "confidence": "medium", "disease": "Implant failure (osseointegration failure)", "glycan_involvement": "Glycosylation affects OPG's stability and bioactivity in the peri-implant environment.", "mechanism": "Decreased OPG levels post-implantation indicate transient inflammation and increased osteoclastic activity, which may compromise osseointegration.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12226070" }, { "confidence": "medium", "disease": "Peri-implantitis", "glycan_involvement": "Therapeutic OPG requires proper glycosylation for efficacy.", "mechanism": "OPG administration or upregulation could inhibit osteoclast-mediated bone loss in peri-implantitis.", "protein": "Osteoprotegerin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226070" }, { "confidence": "high", "disease": "Bone resorption", "glycan_involvement": "Glycosylation enables OPG secretion into GCF.", "mechanism": "OPG levels in gingival crevicular fluid reflect ongoing bone remodeling and resorption status.", "protein": "Osteoprotegerin", "relationship_type": "biomarker", "source_pmcid": "PMC12226070" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation of HBsAg is essential for secretion and immune recognition.", "mechanism": "HBsAg is used for diagnosis of HBV infection; its presence indicates active infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12226165" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Heavily N-glycosylated; glycans shield E2 from immune detection.", "mechanism": "E2 mediates viral entry into hepatocytes, initiating HCV infection.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Altered glycosylation may affect immune evasion and chronicity.", "mechanism": "Chronic HBV infection (persistent HBsAg) leads to liver inflammation and cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycans on E2 modulate immune response and persistence.", "mechanism": "Chronic HCV infection (E2-mediated entry) causes progressive liver damage and cirrhosis.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may influence oncogenic potential.", "mechanism": "Chronic HBV infection increases risk of liver cancer.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycan shielding promotes chronic infection and carcinogenesis.", "mechanism": "Chronic HCV infection is a major risk factor for liver cancer.", "protein": "Hepatitis C virus envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66528" }, "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and serum levels.", "mechanism": "Elevated ALP indicates liver dysfunction in HCV infection.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226165" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "AST is glycosylated; glycosylation may affect serum half-life.", "mechanism": "AST is significantly elevated in HCV-infected patients, indicating liver injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226165" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "ALT is glycosylated; glycosylation may influence activity.", "mechanism": "ALT is elevated in HCV infection, reflecting hepatocellular damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226165" }, { "confidence": "medium", "disease": "Jaundice", "glycan_involvement": "Glycosylation of HBsAg may affect immune-mediated liver injury.", "mechanism": "Acute HBV infection can cause jaundice due to liver dysfunction.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12226165" }, { "confidence": "high", "disease": "Major Depressive Disorder", "glycan_involvement": "N-glycosylation modulates EGFR stability and signaling in neural tissue.", "mechanism": "EGFR mediates air pollution-induced neuroinflammation and altered neurotrophic signaling, increasing depression risk.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226169" }, { "confidence": "high", "disease": "Major Depressive Disorder", "glycan_involvement": "Glycosylation affects IL15 secretion and receptor binding.", "mechanism": "IL15 mediates immune activation and neuroinflammation in response to air pollution, promoting depressive mood.", "protein": "IL15", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226169" }, { "confidence": "high", "disease": "Major Depressive Disorder", "glycan_involvement": "Glycosylation regulates chemokine stability and receptor interaction.", "mechanism": "CCL2 upregulation by air pollution promotes monocyte infiltration and neuroinflammation, contributing to depression.", "protein": "CCL2", "protein_enriched": { "function": "Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:10529171, PubMed:10587439, PubMed:9837883). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobili", "gene_name": "CCL2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P13500" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226169" }, { "confidence": "high", "disease": "Major Depressive Disorder", "glycan_involvement": "Glycosylation modulates chemokine activity and immune cell targeting.", "mechanism": "CCL20 mediates lymphocyte recruitment and neuroinflammatory signaling after air pollution exposure.", "protein": "CCL20", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Binds \u03b2-galactoside glycans, modulating cell\u2013cell interactions.", "mechanism": "Galectin-3 mediates inflammatory responses and may regulate neuroimmune interactions in depression.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "C-type lectin domain binds carbohydrate ligands, modulating immune signaling.", "mechanism": "CLEC4D mediates innate immune activation and inflammation in response to air pollution.", "protein": "CLEC4D", "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "N-glycosylation critical for myelin glycoprotein function.", "mechanism": "OMG involved in myelin integrity and neuronal signaling, affected by air pollution-induced stress.", "protein": "OMG", "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Glycosylation affects cytokine antagonist activity.", "mechanism": "IL1RN modulates inflammatory cytokine signaling, mediating depression risk after air pollution.", "protein": "IL1RN", "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Minimal glycosylation; possible impact on protein stability.", "mechanism": "CASP8 mediates apoptosis and inflammatory signaling in neural cells exposed to air pollution.", "protein": "CASP8", "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "medium", "disease": "Major Depressive Disorder", "glycan_involvement": "Potential O-glycosylation may affect protein\u2013protein interactions.", "mechanism": "FKBP5 regulates cellular stress responses and may mediate air pollution effects on depression.", "protein": "FKBP5", "protein_enriched": { "function": "Immunophilin protein with PPIase and co-chaperone activities (PubMed:11350175). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a", "gene_name": "FKBP5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13451" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226169" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding and clearance.", "mechanism": "Elevated LDL is associated with NAFLD progression; reduction indicates therapeutic improvement.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory properties.", "mechanism": "Decreased HDL is associated with NAFLD; no significant improvement observed with intervention.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "VLDL glycosylation influences secretion and metabolism.", "mechanism": "VLDL levels are altered in NAFLD; no significant change with treatment.", "protein": "VLDL", "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "ALT is glycosylated, which may affect stability and serum half-life.", "mechanism": "Elevated ALT indicates liver injury in NAFLD; synbiotic treatment reduces ALT.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "AST glycosylation may influence enzyme activity.", "mechanism": "AST elevation marks liver injury; no significant improvement with intervention.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "ALP glycosylation affects enzyme activity and secretion.", "mechanism": "ALP is elevated in liver dysfunction; no significant change with treatment.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation modulates LDL receptor interaction and hepatic uptake.", "mechanism": "LDL accumulation contributes to hepatic steatosis and inflammation.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC12226277" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation may affect LDL clearance and fibrogenesis.", "mechanism": "Chronic LDL elevation promotes fibrotic progression in liver.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC12226277" }, { "confidence": "low", "disease": "Hepatic carcinoma", "glycan_involvement": "Glycosylation changes may influence LDL's role in carcinogenesis.", "mechanism": "Persistent dyslipidemia (high LDL) is a risk factor for hepatic carcinoma.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC12226277" }, { "confidence": "medium", "disease": "Steatohepatitis (NASH)", "glycan_involvement": "HDL glycosylation enhances anti-inflammatory effects.", "mechanism": "Higher HDL levels are protective against progression to NASH.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC12226277" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "ZO-1 is glycosylated, which is important for its localization and function.", "mechanism": "Upregulation of ZO-1 by HDCA enhances tight junction integrity, reducing barrier dysfunction.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12226288" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Claudins are glycoproteins; glycosylation affects tight junction assembly.", "mechanism": "HDCA increases Claudin expression, strengthening barrier function.", "protein": "Claudin", "relationship_type": "protective", "source_pmcid": "PMC12226288" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Occludin glycosylation is required for tight junction stability.", "mechanism": "HDCA upregulates Occludin, improving barrier integrity.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12226288" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "TGR5 is glycosylated, which modulates receptor function.", "mechanism": "HDCA activates TGR5 signaling, suppressing pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6).", "protein": "TGR5 (GPBAR1)", "protein_enriched": { "function": "Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macr", "gene_name": "GPBAR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8TDU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226288" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "CYP7A1 is glycosylated, affecting enzyme stability.", "mechanism": "HDCA upregulates CYP7A1 in intestine, modulating bile acid synthesis and improving metabolic profile.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226288" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "IgG glycosylation modulates effector function and anti-inflammatory activity.", "mechanism": "HDCA increases serum IgG, enhancing immune defense against inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12226288" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "ASBT glycosylation affects transporter activity.", "mechanism": "HDCA downregulates ASBT, altering bile acid reabsorption and microbiota composition.", "protein": "ASBT (SLC10A2)", "protein_enriched": { "function": "Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:7592981, PubMed:9458785, PubMed:9856990). Transports various bile acids, unconjug", "gene_name": "SLC10A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q12908" }, "relationship_type": "causal", "source_pmcid": "PMC12226288" }, { "confidence": "medium", "disease": "Metabolic disorders", "glycan_involvement": "SHP is glycosylated, influencing nuclear receptor function.", "mechanism": "HDCA upregulates SHP, modulating bile acid feedback and metabolic homeostasis.", "protein": "SHP (NR0B2)", "protein_enriched": { "function": "Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golg", "gene_name": "ARFGEF1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10488MI", "G72787SB", "G49108TO" ], "uniprot_id": "Q9Y6D6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226288" }, { "confidence": "low", "disease": "Colitis", "glycan_involvement": "CYP4A27 glycosylation may affect enzyme activity.", "mechanism": "HDCA upregulates CYP4A27 in ileum, potentially reducing inflammation.", "protein": "CYP4A27", "relationship_type": "protective", "source_pmcid": "PMC12226288" }, { "confidence": "high", "disease": "Lipopolysaccharide-induced inflammation", "glycan_involvement": "TGR5 glycosylation modulates receptor signaling.", "mechanism": "HDCA activation of TGR5 reduces LPS-induced cytokine production.", "protein": "TGR5 (GPBAR1)", "protein_enriched": { "function": "Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macr", "gene_name": "GPBAR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8TDU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226288" }, { "confidence": "high", "disease": "T-cell leukemia", "glycan_involvement": "CD2 is a glycoprotein; glycosylation affects cell adhesion and immune recognition.", "mechanism": "Upregulated in T-cell lineage and leukemia virus infection pathways, indicating T-cell activation.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226298" }, { "confidence": "high", "disease": "T-cell leukemia", "glycan_involvement": "N-glycosylation modulates T-cell receptor interactions.", "mechanism": "Upregulated in hematopoietic cell lineage and viral infection pathways; marker of cytotoxic T-cell activation.", "protein": "CD8B", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "Cd8b", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P10300" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226298" }, { "confidence": "high", "disease": "Immunodeficiency", "glycan_involvement": "Glycosylation required for surface expression and stability.", "mechanism": "Essential for TCR-CD3 complex; deficiency leads to severe immunodeficiency.", "protein": "CD3G", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P09693" }, "relationship_type": "causal", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation critical for IgG binding and transport.", "mechanism": "Mediates IgG recycling and transport, sustaining antibody-mediated immunity.", "protein": "FCGRT", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8MJZ1" }, "relationship_type": "protective", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation enhances stability and secretion.", "mechanism": "Inhibits proteases and modulates inflammation; upregulated in immune response.", "protein": "SLPI", "relationship_type": "protective", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation regulates ligand binding and signaling.", "mechanism": "Upregulated in cancer pathways; mediates cell adhesion and migration.", "protein": "ITGB1", "relationship_type": "biomarker", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "O-glycosylation modulates chemokine activity.", "mechanism": "Key chemokine in neutrophil recruitment and inflammatory response.", "protein": "CXCL8", "relationship_type": "biomarker", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Allergy", "glycan_involvement": "Indirect; glycosylation of upstream cytokine receptors modulates STAT5A activation.", "mechanism": "Regulates Th1/Th2 differentiation; imbalance linked to allergy and immune disorders.", "protein": "STAT5A", "relationship_type": "causal", "source_pmcid": "PMC12226298" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation affects protein stability and activation.", "mechanism": "Component of inflammasome; mediates IL-1\u03b2 production and inflammatory diseases.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12226298" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation required for PD-L1 stability and function.", "mechanism": "Immune checkpoint ligand; upregulation enables tumor immune evasion.", "protein": "CD274", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226298" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "HA is heavily glycosylated, which affects immune recognition and viral infectivity.", "mechanism": "HA mediates viral entry into host cells via sialic acid binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12226393" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Stalk glycosylation modulates antibody accessibility and immune evasion.", "mechanism": "Antibodies targeting the conserved HA stalk confer broad protection by neutralizing diverse influenza subtypes.", "protein": "HA stalk domain", "relationship_type": "protective", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Severe influenza (H5N1)", "glycan_involvement": "Glycosylation patterns influence stalk antibody binding.", "mechanism": "Early-life exposure or vaccination inducing group 1 HA stalk antibodies protects against severe H5N1 disease.", "protein": "HA stalk domain", "relationship_type": "protective", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Severe influenza (H7N9)", "glycan_involvement": "Glycosylation affects stalk antigenicity and immune imprinting.", "mechanism": "Early-life exposure or vaccination inducing group 2 HA stalk antibodies protects against severe H7N9 disease.", "protein": "HA stalk domain", "relationship_type": "protective", "source_pmcid": "PMC12226393" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "NA is glycosylated, which can modulate immune recognition.", "mechanism": "NA cleaves sialic acids to facilitate viral release; anti-NA antibodies can block infection and transmission.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226393" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "sIgA is heavily glycosylated, enhancing stability and mucosal transport.", "mechanism": "Mucosal sIgA can neutralize virus at entry sites, preventing infection and transmission.", "protein": "Secretory IgA (sIgA)", "relationship_type": "protective", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Seasonal influenza", "glycan_involvement": "Glycosylation state affects stalk antibody detection and function.", "mechanism": "Serum anti-stalk antibody titers correlate with protection in community studies.", "protein": "HA stalk domain", "relationship_type": "biomarker", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Glycan shielding may limit vaccine efficacy by masking epitopes.", "mechanism": "Universal vaccines targeting the HA stalk aim to induce broad, cross-protective immunity.", "protein": "HA stalk domain", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Glycosylation can modulate Fc-mediated effector functions.", "mechanism": "Stalk-reactive antibodies induced by LAIV mediate ADCC, contributing to viral clearance.", "protein": "HA stalk domain", "relationship_type": "protective", "source_pmcid": "PMC12226393" }, { "confidence": "medium", "disease": "Seasonal influenza", "glycan_involvement": "NA glycosylation affects antibody binding and immune response.", "mechanism": "Serum anti-NA antibody levels are associated with reduced infection risk.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226393" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Elevated VEGF-\u03b1 promotes angiogenesis and tumor progression.", "protein": "VEGF-\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation affects stability and bioactivity.", "mechanism": "VEGF-\u03b1 upregulated in cirrhosis, indicating increased angiogenic activity.", "protein": "VEGF-\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Removes fucose from glycoproteins; altered activity marks glycan remodeling in cancer.", "mechanism": "Serum AFU elevated in HCC, reflecting altered glycan degradation.", "protein": "\u03b1-L-fucosidase (AFU)", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "HA is a glycosaminoglycan; its accumulation reflects ECM glycan remodeling.", "mechanism": "Serum HA increases with ECM deposition during fibrosis.", "protein": "Hyaluronic acid (HA)", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects secretion and ECM incorporation.", "mechanism": "Elevated PIIINP indicates active collagen synthesis and fibrosis.", "protein": "Type III procollagen (PIIINP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation required for secretion and receptor interaction.", "mechanism": "TGF-\u03b2 drives fibroblast activation and ECM deposition.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates cell adhesion and angiogenesis.", "mechanism": "CD34 marks tumor angiogenesis; upregulated in HCC.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Targeting glycosylated VEGF-\u03b1 may affect its bioactivity.", "mechanism": "Sevelamer reduces VEGF-\u03b1, inhibiting angiogenesis and tumor growth.", "protein": "VEGF-\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226404" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation essential for TGF-\u03b2 function.", "mechanism": "Sevelamer downregulates TGF-\u03b2, reducing fibrosis.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226404" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Fucosidase activity alters glycoprotein structure in disease.", "mechanism": "AFU elevation reflects glycan turnover in cirrhotic liver.", "protein": "\u03b1-L-fucosidase (AFU)", "relationship_type": "biomarker", "source_pmcid": "PMC12226404" }, { "confidence": "high", "disease": "Sepsis-induced AKI", "glycan_involvement": "N-glycosylation required for chaperone function and ER localization.", "mechanism": "Elevated GRP78 expression marks ER stress and apoptosis in renal tubular cells; inhibition alleviates immune response and oxidative stress.", "protein": "GRP78/BiP", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12226596" }, { "confidence": "high", "disease": "Sepsis-induced AKI", "glycan_involvement": "N-glycosylation supports folding and chaperone activity.", "mechanism": "GRP170 knockout induces AKI phenotype; presence protects against ER stress-induced apoptosis.", "protein": "GRP170", "relationship_type": "causal/protective", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "N-glycosylation essential for glycoprotein folding cycle.", "mechanism": "Calnexin binds Ca2+ and assists glycoprotein folding in ER; dysfunction contributes to ER stress in AKI.", "protein": "Calnexin", "relationship_type": "biomarker", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Contrast-induced AKI (CI-AKI)", "glycan_involvement": "Glycosylation regulates ATF6 activation and trafficking.", "mechanism": "Upregulated by contrast agents, mediates ER stress and apoptosis; inhibition reduces renal injury.", "protein": "ATF6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Contrast-induced AKI (CI-AKI)", "glycan_involvement": "Indirect; downstream of glycoprotein folding stress.", "mechanism": "CHOP upregulation triggers apoptosis in renal tubular cells during ER stress.", "protein": "CHOP", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Binds high-mannose N-glycans on misfolded proteins.", "mechanism": "EDEM recognizes misfolded glycoproteins for ERAD; increased activity during ER stress in AKI.", "protein": "EDEM", "protein_enriched": { "function": "Involved in the endoplasmic reticulum-associated degradation (ERAD) pathway that targets misfolded glycoproteins for degradation in an N-glycan-dependent manner (PubMed:15537790, PubMed:25092655). May", "gene_name": "EDEM2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9BV94" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Binds N-glycans for substrate recognition.", "mechanism": "OS9 participates in ERAD, recognizing misfolded glycoproteins during ER stress.", "protein": "OS9", "protein_enriched": { "function": "Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins", "gene_name": "SACS", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G47644PP" ], "uniprot_id": "Q9NZJ4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may regulate receptor function.", "mechanism": "FAM134B mediates ER-phagy, clearing damaged ER and protecting against prolonged ER stress.", "protein": "FAM134B", "protein_enriched": { "function": "Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (PubMed:11095750). Downstream effector of Notch signaling required for cardiovascular development. Spe", "gene_name": "HEY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5J3" }, "relationship_type": "protective", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Potential N-glycosylation modulates activity.", "mechanism": "SEC62 acts as ER-phagy receptor, facilitating removal of dysfunctional ER during stress.", "protein": "SEC62", "protein_enriched": { "function": "Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar s", "gene_name": "SEC62", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99442" }, "relationship_type": "protective", "source_pmcid": "PMC12226596" }, { "confidence": "medium", "disease": "Cisplatin-induced AKI", "glycan_involvement": "Not directly glycosylated; acts downstream of glycoprotein stress.", "mechanism": "Activated by ER stress, calpain triggers cell death in renal tissue.", "protein": "Calpain", "protein_enriched": { "function": "Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:19617626, PubMed:21531719, PubMed:2", "gene_name": "CAPN1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "P07384" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226596" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "ALK3 is a glycoprotein receptor; glycosylation may affect ligand binding and signaling.", "mechanism": "ALK3+ ductal progenitors respond to BMP signaling, proliferate, and differentiate into insulin-producing \u03b2-cells.", "protein": "ALK3 (BMP receptor 1A)", "protein_enriched": { "function": "Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulati", "gene_name": "ACVR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q04771" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226732" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "BMP-7 is a glycoprotein; glycosylation is important for secretion and receptor interaction.", "mechanism": "BMP-7 activates ductal progenitors to regenerate \u03b2-cells in situ.", "protein": "BMP-7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226732" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "Acts via glycoprotein receptor ALK3; not itself a glycoprotein.", "mechanism": "THR-123 (BMP-7-like peptide) stimulates ALK3+ ductal cells to regenerate \u03b2-cells, reducing hyperglycemia.", "protein": "THR-123", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226732" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Krt7 is a glycoprotein; glycosylation may affect filament assembly.", "mechanism": "Krt7+ ductal structures are found within neogenic islets, indicating ductal origin of new \u03b2-cells.", "protein": "Krt7 (Cytokeratin 7)", "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Heavily glycosylated; glycosylation critical for cell-cell interactions.", "mechanism": "CD24 marks BMP-7-responsive ductal progenitors capable of \u03b2-cell neogenesis.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "high", "disease": "Type 1 diabetes", "glycan_involvement": "Insulin is glycosylated; glycosylation affects stability and secretion.", "mechanism": "Loss of insulin-producing \u03b2-cells causes hyperglycemia; regeneration restores normoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12226732" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may affect receptor function and localization.", "mechanism": "P2RY1 marks ALK3+ ductal progenitors responsive to BMP signaling.", "protein": "P2RY1", "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may modulate filament properties.", "mechanism": "Krt19 distinguishes ductal from intrainsular ductal tissue in islet neogenesis.", "protein": "Krt19 (Cytokeratin 19)", "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may affect nuclear localization and function.", "mechanism": "HNF1\u03b2 marks ductal progenitors with organoid-forming and regenerative capacity.", "protein": "HNF1\u03b2", "protein_enriched": { "function": "Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity).", "gene_name": "HNF1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35680" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may regulate protein stability.", "mechanism": "Sox9+ ductal cells are progenitors for \u03b2-cell neogenesis upon BMP signaling.", "protein": "Sox9", "protein_enriched": { "function": "Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:24038782). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enha", "gene_name": "SOX9", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48436" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226732" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin is N-glycosylated; altered glycosylation may affect stability and clearance.", "mechanism": "Serum albumin levels reflect liver synthetic function; decreased in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226860" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "ALT is glycosylated; glycosylation may affect serum half-life.", "mechanism": "ALT is released from damaged hepatocytes; elevated in liver injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226860" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "AST is glycosylated; glycosylation may affect stability.", "mechanism": "AST is released from damaged hepatocytes; elevated in liver injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226860" }, { "confidence": "medium", "disease": "Hypersplenism", "glycan_involvement": "Glycosylation patterns on WBCs influence recognition and clearance by splenic macrophages.", "mechanism": "WBCs are sequestered and destroyed in the enlarged spleen due to altered recognition of surface glycoproteins.", "protein": "White blood cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12226860" }, { "confidence": "medium", "disease": "Hypersplenism", "glycan_involvement": "Altered glycosylation can enhance splenic clearance.", "mechanism": "Platelets are sequestered and destroyed in the spleen; surface glycoproteins mediate recognition.", "protein": "Platelet surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12226860" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Altered glycosylation may affect albumin function and vascular effects.", "mechanism": "Low albumin reflects portal hypertension severity due to impaired synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12226860" }, { "confidence": "medium", "disease": "Leukopenia", "glycan_involvement": "Glycosylation affects susceptibility to splenic phagocytosis.", "mechanism": "Destruction of WBCs in hypersplenism leads to leukopenia.", "protein": "White blood cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12226860" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycan modifications modulate platelet clearance.", "mechanism": "Platelet destruction in hypersplenism leads to thrombocytopenia.", "protein": "Platelet surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12226860" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect stability and cell-surface localization.", "mechanism": "Upregulated in activated hepatic stellate cells during fibrosis; reduced by TACS and L. reuteri treatment.", "protein": "Alpha-smooth muscle actin (\u03b1-SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12226865" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation critical for collagen fibril formation.", "mechanism": "Major ECM glycoprotein accumulated in fibrotic liver; reduced by TACS and L. reuteri.", "protein": "Collagen type I alpha 1 (COL1A1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12226865" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates secretion and receptor binding.", "mechanism": "Pro-inflammatory cytokine elevated in LF; reduced by TACS and L. reuteri.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12226865" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects stability and activity.", "mechanism": "Elevated in LF; reduced by TACS and L. reuteri.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12226865" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences secretion.", "mechanism": "Promotes hepatic stellate cell activation and inflammation; reduced by TACS and L. reuteri.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "causal", "source_pmcid": "PMC12226865" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect receptor function.", "mechanism": "Activated by CDCA; FXR-FGF19 signaling inhibits bile acid synthesis and fibrosis.", "protein": "Farnesoid X receptor (FXR)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12226865" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Induced by FXR activation; inhibits bile acid synthesis, reducing fibrosis.", "protein": "Fibroblast growth factor 19 (FGF19)", "protein_enriched": { "function": "Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocyte", "gene_name": "FGF19", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95750" }, "relationship_type": "protective", "source_pmcid": "PMC12226865" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "Activated by FGF19; inhibits bile acid synthesis, reducing fibrosis.", "protein": "FGF receptor 4 (FGFR4)", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of", "gene_name": "FGFR4", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G22310AV", "G80920RR", "G43417UB", "G13694XX", "G48414YA", "G33791AF", "G47748JZ", "G83460ZZ", "G84452RH", "G86795LJ" ], "uniprot_id": "P22455" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12226865" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may regulate activation.", "mechanism": "Activated by DCA and CDCA; mediates pyroptosis and inflammation in LF.", "protein": "Caspase-11", "protein_enriched": { "function": "Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:22002608, PubMed:23348507, PubMed:23887873, PubMed:240", "gene_name": "Casp4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P70343" }, "relationship_type": "causal", "source_pmcid": "PMC12226865" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Bacterial glycoproteins may interact with host mucins and immune receptors.", "mechanism": "Enrichment by TACS and direct administration ameliorates LF via modulation of bile acid metabolism and anti-inflammatory effects.", "protein": "Lactobacillus reuteri surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12226865" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "BMP interacts with glycosphingolipids in lysosomes, influencing glycan metabolism.", "mechanism": "BMP levels in urine and blood reflect lysosomal lipid metabolism changes in mCRPC and response to therapy.", "protein": "Bis(monoacylglycero)phosphate (BMP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "PSA is a glycoprotein; its glycosylation affects stability and detection.", "mechanism": "PSA levels are used to monitor disease progression and response to therapy.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "ASM is glycosylated, which is essential for its lysosomal localization and function.", "mechanism": "CADs inhibit ASM by disrupting BMP interaction, leading to sphingomyelin buildup and lysosomal membrane permeabilization.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226910" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "BMP modulates glycosphingolipid metabolism in lysosomes.", "mechanism": "Altered BMP levels indicate lysosomal dysfunction in prostate cancer cells.", "protein": "Bis(monoacylglycero)phosphate (BMP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "ASM glycosylation is necessary for enzymatic activity.", "mechanism": "ASM activity is required for sphingomyelin breakdown; its inhibition leads to lysosomal stress and cell death.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "causal", "source_pmcid": "PMC12226910" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA glycosylation patterns may change in cancer, affecting immunodetection.", "mechanism": "PSA is a standard biomarker for prostate cancer diagnosis and monitoring.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "BMP regulates glycosphingolipid catabolism, impacting glycan turnover.", "mechanism": "Targeting BMP-ASM interaction with CADs induces lysosomal cell death in chemotherapy-resistant cells.", "protein": "Bis(monoacylglycero)phosphate (BMP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12226910" }, { "confidence": "medium", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "ASM glycosylation is required for lysosomal targeting and function.", "mechanism": "ASM inhibition by CADs sensitizes resistant cancer cells to chemotherapy.", "protein": "Acid sphingomyelinase (ASM)", "protein_enriched": { "function": "Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from", "gene_name": "SMPD1", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G43769HG", "G10756ZZ", "G08290VR", "G36670VW", "G91473PK", "G49108TO" ], "uniprot_id": "P17405" }, "relationship_type": "protective", "source_pmcid": "PMC12226910" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Altered glycosylation may affect PSA clearance and detection.", "mechanism": "PSA reduction correlates with therapeutic response in mCRPC.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "BMP influences glycosphingolipid turnover in lysosomes.", "mechanism": "BMP changes serve as translational indicators of lysosomal lipid metabolism in response to therapy.", "protein": "Bis(monoacylglycero)phosphate (BMP)", "relationship_type": "biomarker", "source_pmcid": "PMC12226910" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Increased glycation (non-enzymatic) of hemoglobin.", "mechanism": "Reflects average blood glucose via non-enzymatic glycation of hemoglobin.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects insulin stability and receptor interaction.", "mechanism": "Serum insulin levels indicate insulin resistance status.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "C-peptide is a glycoprotein; glycosylation may affect its half-life.", "mechanism": "C-peptide reflects endogenous insulin secretion.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may affect enzyme stability and serum levels.", "mechanism": "Elevated ALT indicates hepatocellular injury in NAFLD.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Elevated AST is associated with liver injury in NAFLD.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation of apolipoproteins affects HDL function.", "mechanism": "Low HDL is associated with increased NAFLD risk; HDL has anti-inflammatory effects.", "protein": "HDL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "Elevated LDL is associated with lipid accumulation in NAFLD.", "protein": "LDL", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor interaction.", "mechanism": "Pro-inflammatory cytokine promotes hepatic inflammation and progression of NAFLD.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12227005" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation regulates IL-6 stability and signaling.", "mechanism": "IL-6 mediates chronic inflammation, contributing to NAFLD progression.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12227005" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate ER\u03b1 function and signaling.", "mechanism": "ER\u03b1 activation improves insulin sensitivity and protects against NAFLD.", "protein": "Estrogen receptor alpha (ER\u03b1)", "relationship_type": "protective", "source_pmcid": "PMC12227005" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin N-terminus", "mechanism": "HbA1c reflects average blood glucose and is used for diagnosis and monitoring of T2DM.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Visceral obesity (VO)", "glycan_involvement": "Non-enzymatic glycation", "mechanism": "Higher HbA1c levels are associated with increased VO in T2DM patients.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Visceral obesity (VO)", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation may affect function", "mechanism": "Lower HDL-C levels are associated with increased VO in T2DM patients.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Visceral obesity (VO)", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB) with glycan modifications influencing metabolism", "mechanism": "Higher LDL-C levels are associated with increased VO in T2DM patients.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "high", "disease": "Microvascular complications of diabetes", "glycan_involvement": "Non-enzymatic glycation", "mechanism": "Elevated HbA1c is predictive of increased risk for microvascular complications.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of HDL proteins may modulate lipid metabolism", "mechanism": "Low HDL-C is a component of dyslipidemia, which is associated with VO and T2DM.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of LDL proteins may modulate lipid metabolism", "mechanism": "High LDL-C is a component of dyslipidemia, which is associated with VO and T2DM.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Glycosylation of HDL proteins may affect anti-inflammatory properties", "mechanism": "Low HDL-C is associated with increased risk of NAFLD, especially in VO and T2DM.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Non-enzymatic glycation", "mechanism": "Higher HbA1c reflects poor glycemic control and is associated with increased insulin resistance.", "protein": "Glycated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation of HDL proteins may affect cholesterol efflux", "mechanism": "Low HDL-C is a diagnostic criterion for metabolic syndrome, which is linked to VO and T2DM.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12227006" }, { "confidence": "high", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "ApoE is N-glycosylated, affecting its stability and immune modulation.", "mechanism": "High ApoE levels are positively correlated with increased mortality in ARI; may impair macrophage function and promote inflammation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "high", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "LDL contains glycosylated ApoB, influencing receptor interactions.", "mechanism": "Low LDL levels are inversely correlated with mortality; may reflect impaired pathogen clearance and poor nutritional status.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "high", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "sdLDL contains glycosylated ApoB; glycosylation may affect particle clearance.", "mechanism": "Low sdLDL levels are associated with higher mortality; may impair immune cell membrane integrity and antiviral response.", "protein": "Small Dense LDL (sdLDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ApoE may modulate spike protein binding.", "mechanism": "ApoE interacts with SARS-CoV-2 spike protein, facilitating viral infection and altering immune response.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12227315" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation status may influence ApoE4 function.", "mechanism": "ApoE4 variant impairs microglial function, affecting immune clearance.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12227315" }, { "confidence": "medium", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "HbA1c is a non-enzymatic glycation product, not classical glycosylation.", "mechanism": "HbA1c levels show a parabolic association with mortality at high FBG; acute hyperglycemia is more predictive than chronic glycation.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "medium", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "D-dimer is glycosylated, affecting its clearance and detection.", "mechanism": "High D-dimer levels are associated with increased mortality, reflecting coagulation activation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "medium", "disease": "Severe Pneumonia", "glycan_involvement": "N-glycosylation may affect ApoE's immune regulatory functions.", "mechanism": "ApoE levels are lower in severe pneumonia compared to non-severe cases, indicating immune modulation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "low", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "ApoA1 is glycosylated, influencing lipid transport and immune function.", "mechanism": "Lower ApoA1 levels are associated with higher mortality, possibly due to impaired anti-inflammatory effects.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective", "source_pmcid": "PMC12227315" }, { "confidence": "low", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "SAA is glycosylated, affecting its solubility and immune signaling.", "mechanism": "High SAA levels are associated with increased mortality, reflecting acute phase response.", "protein": "Serum Amyloid A protein (SAA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227315" }, { "confidence": "high", "disease": "Retinal degeneration", "glycan_involvement": "N-glycosylation at Asn190 may affect TauT stability and function.", "mechanism": "TauT dysfunction leads to low intracellular taurine, inducing retinal degeneration.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "N-glycosylation at Asn190 may impact TauT trafficking and stability.", "mechanism": "TauT dysfunction causes taurine deficiency, resulting in cardiomyopathy.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Neurological disorder", "glycan_involvement": "N-glycosylation may modulate TauT localization in neurons.", "mechanism": "TauT dysfunction reduces taurine uptake, affecting neuronal function.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Muscle weakness and fatigue", "glycan_involvement": "N-glycosylation may affect TauT stability in muscle cells.", "mechanism": "TauT dysfunction leads to taurine deficiency, impairing muscle function.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Metabolic dysregulation", "glycan_involvement": "N-glycosylation may regulate TauT activity in metabolic tissues.", "mechanism": "TauT dysfunction disrupts taurine homeostasis, leading to metabolic issues.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Aging-associated disorders", "glycan_involvement": "N-glycosylation may influence TauT stability during aging.", "mechanism": "TauT dysfunction and decreased taurine biosynthesis contribute to aging-related decline.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation may affect TauT expression in cancer cells.", "mechanism": "TauT is implicated in tumor progression and recurrence; potential target for therapy.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227546" }, { "confidence": "high", "disease": "Retinal degeneration", "glycan_involvement": "No direct glycan involvement for this mutation.", "mechanism": "Gly399Val mutation in TauT abolishes activity and induces retinal degeneration.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "high", "disease": "Cardiomyopathy", "glycan_involvement": "No direct glycan involvement for this mutation.", "mechanism": "Gly399Val mutation in TauT abolishes activity and induces cardiomyopathy.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "medium", "disease": "Retinal degeneration", "glycan_involvement": "N-glycosylation may affect TauT trafficking in retinal cells.", "mechanism": "TauT dysfunction impairs taurine transport across blood-retinal barrier.", "protein": "Taurine transporter (TauT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Ca", "gene_name": "SLC6A6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G62765YT" ], "uniprot_id": "P31641" }, "relationship_type": "causal", "source_pmcid": "PMC12227546" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "CD4 is a glycoprotein; glycosylation is essential for its stability and function in T-cell signaling.", "mechanism": "Reduced plasma CD4 in PD reflects immune dysregulation; therapies increasing CD4 may confer neuroprotection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "sTfR glycosylation affects its solubility and detection in plasma.", "mechanism": "Elevated sTfR/log ferritin ratio in PD rats indicates iron deficiency anemia.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Ferritin glycosylation modulates its stability and secretion.", "mechanism": "Decreased plasma ferritin in PD model reflects impaired iron storage and anemia.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "DMT1 glycosylation may affect its trafficking and iron transport activity.", "mechanism": "Upregulation of DMT1 in PD brain promotes iron accumulation, oxidative stress, and neurodegeneration; downregulation by synbiotic/chocolate is protective.", "protein": "DMT1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "DRD1 glycosylation is important for receptor localization and ligand binding.", "mechanism": "Downregulation of DRD1 in PD impairs dopaminergic signaling; upregulation by synbiotic/chocolate improves neuronal function.", "protein": "DRD1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor interaction.", "mechanism": "Elevated TNF-\u03b1 in PD brain drives neuroinflammation and iron dysregulation; reduced by synbiotic/chocolate.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12227552" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IFN-\u03b3 glycosylation modulates its stability and immune signaling.", "mechanism": "Increased plasma IFN-\u03b3 in PD reflects systemic inflammation; normalized by synbiotic/chocolate.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation of CD4 is critical for T-cell receptor interaction.", "mechanism": "CD4+ T-cell activity is reduced in PD, contributing to neuroinflammation; restoration may be neuroprotective.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "protective", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Aggregation of \u03b1-synuclein (Lewy bodies) is a hallmark of PD pathology.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects sTfR plasma levels and function.", "mechanism": "Elevated sTfR/log ferritin ratio in PD reflects iron metabolism disturbance linked to neurodegeneration.", "protein": "Soluble transferrin receptor (sTfR)", "relationship_type": "biomarker", "source_pmcid": "PMC12227552" }, { "confidence": "high", "disease": "Colorectal polyps", "glycan_involvement": "CEA is highly N-glycosylated; glycosylation affects its stability and detection.", "mechanism": "Elevated serum CEA is associated with increased risk and presence of colorectal polyps.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "high", "disease": "Colorectal adenomatous polyps", "glycan_involvement": "Altered glycosylation may affect CEA's role in cell adhesion and tumorigenesis.", "mechanism": "CEA levels are higher in patients with adenomatous polyps, indicating progression risk.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation modulates CEA's immunogenicity and detection.", "mechanism": "CEA is a classic marker for colorectal cancer progression from polyps.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "medium", "disease": "Colorectal polyps", "glycan_involvement": "N-glycosylation affects ApoB's lipid transport and possibly its role in polyp recurrence.", "mechanism": "Higher ApoB levels are associated with increased risk of colorectal polyps.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may influence ApoB's stability and function in lipid metabolism.", "mechanism": "ApoB is implicated in recurrence risk after polyp removal, possibly linking to cancer risk.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "medium", "disease": "Colorectal polyps", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation may affect anti-inflammatory properties.", "mechanism": "Lower HDL-C levels are associated with higher risk of colorectal polyps; HDL-C is protective.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12227555" }, { "confidence": "low", "disease": "Colorectal polyps", "glycan_involvement": "Glycosylation may modulate ApoA-I's anti-inflammatory and lipid transport functions.", "mechanism": "Lower ApoA-I levels trend with increased polyp risk, though not statistically significant.", "protein": "Apolipoprotein A-I (ApoA-I)", "relationship_type": "protective", "source_pmcid": "PMC12227555" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation status may be altered in metabolic syndrome, affecting CEA levels.", "mechanism": "CEA levels are elevated in metabolic syndrome, which is a risk factor for polyps.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "Altered glycosylation may affect CEA's serum levels in insulin resistance.", "mechanism": "CEA is elevated in insulin resistance, which correlates with polyp risk.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "N-glycosylation may affect ApoB's function in metabolic syndrome.", "mechanism": "ApoB is elevated in metabolic syndrome, which increases risk for colorectal polyps.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12227555" }, { "confidence": "high", "disease": "Still's disease", "glycan_involvement": "Non-glycosylated ferritin is increased, amplifying serum levels.", "mechanism": "Extreme hyperferritinemia due to cytokine-driven acute-phase response and increased secretion of non-glycosylated ferritin by activated macrophages.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Intravascular lymphoma (IVL)", "glycan_involvement": "Possible increase in non-glycosylated ferritin, but data for IVL lacking.", "mechanism": "Ferritin moderately elevated due to chronic inflammation, tumor necrosis, or sHLH, but less than in Still's disease.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "high", "disease": "Intravascular lymphoma (IVL)", "glycan_involvement": "sIL-2R is a glycoprotein shed from activated lymphocytes.", "mechanism": "Markedly elevated sIL-2R reflects lymphocyte activation and tumor cell proliferation.", "protein": "sIL-2R", "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Still's disease", "glycan_involvement": "sIL-2R glycosylation not specifically discussed.", "mechanism": "Mild elevation due to self-inflammatory process, but lower than in IVL.", "protein": "sIL-2R", "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "high", "disease": "Still's disease", "glycan_involvement": "IL-18 is a glycoprotein; glycosylation not specifically discussed.", "mechanism": "Markedly elevated IL-18 due to inflammasome activation; central to pathogenesis and risk for sHLH.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Intravascular lymphoma (IVL)", "glycan_involvement": "IL-18 glycosylation not specifically discussed.", "mechanism": "Mild to moderate elevation, especially in IVL complicated by sHLH, but consistently lower than in Still's disease.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Secondary hemophagocytic lymphohistiocytosis (sHLH)", "glycan_involvement": "Non-glycosylated ferritin may be increased.", "mechanism": "Elevated ferritin is a marker of sHLH, but not discriminatory between IVL and Still's disease.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Secondary hemophagocytic lymphohistiocytosis (sHLH)", "glycan_involvement": "sIL-2R glycosylation not specifically discussed.", "mechanism": "Elevated sIL-2R in sHLH, similar to IVL.", "protein": "sIL-2R", "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Secondary hemophagocytic lymphohistiocytosis (sHLH)", "glycan_involvement": "IL-18 glycosylation not specifically discussed.", "mechanism": "Elevated IL-18 in sHLH, but levels in Still's disease are higher.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "high", "disease": "Still's disease", "glycan_involvement": "Decrease in glycosylation increases serum ferritin.", "mechanism": "Non-glycosylated ferritin secreted by macrophages is cleared slowly, amplifying hyperferritinemia.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "mechanistic biomarker", "source_pmcid": "PMC12227761" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Albumin glycosylation may influence its binding and pharmacokinetics.", "mechanism": "Higher serum albumin levels are associated with increased dose-adjusted amlodipine concentration, potentially affecting antihypertensive response.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "CRP glycosylation modulates its stability and function in inflammation.", "mechanism": "Elevated CRP levels are associated with increased dose-adjusted amlodipine concentration, reflecting inflammation's impact on drug metabolism.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects CYP3A4 folding and membrane localization.", "mechanism": "CYP3A4 metabolizes amlodipine; reduced activity (e.g., CYP3A4*22 allele) increases serum drug concentration and may enhance antihypertensive effect.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may influence CYP3A5 stability and activity.", "mechanism": "CYP3A5 genetic variants affect amlodipine metabolism, but no significant association with drug concentration in this cohort.", "protein": "Cytochrome P450 3A5 (CYP3A5)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen ", "gene_name": "CYP3A5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20815" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Reduced kidney function", "glycan_involvement": "Altered glycosylation in kidney disease affects albumin function.", "mechanism": "Serum albumin levels are altered in renal dysfunction, impacting drug binding and pharmacokinetics.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation regulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in chronic inflammation, correlating with changes in drug metabolism and hypertension risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "high", "disease": "Uncontrolled hypertension", "glycan_involvement": "Glycosylation may modulate enzyme activity and drug metabolism.", "mechanism": "Reduced CYP3A4 activity leads to higher amlodipine concentration, lowering risk of uncontrolled hypertension.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "causal", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Uncontrolled hypertension", "glycan_involvement": "Glycosylation status may affect albumin's drug-binding capacity.", "mechanism": "Higher albumin levels are associated with increased amlodipine concentration, potentially reducing uncontrolled hypertension risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Uncontrolled hypertension", "glycan_involvement": "Glycosylation influences CRP's role in vascular inflammation.", "mechanism": "Elevated CRP is linked to higher amlodipine concentration, possibly improving blood pressure control.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227894" }, { "confidence": "medium", "disease": "Reduced kidney function", "glycan_involvement": "Glycosylation may affect CYP3A4's response to metabolic changes in kidney disease.", "mechanism": "Renal impairment may decrease hepatic metabolism via CYP3A4, increasing amlodipine concentration.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "causal", "source_pmcid": "PMC12227894" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "N-glycosylation critical for CD36 trafficking and function.", "mechanism": "CD36 facilitates intestinal long-chain fatty acid absorption; deficiency alters triglyceride and cholesterol uptake.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12227904" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP is a biomarker and mediator of low-grade inflammation in MetS; transgenic human CRP increases inflammatory response.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation required for ABCG5 membrane localization.", "mechanism": "ABCG5 downregulation reduces sterol transport, increasing hepatic cholesterol and altering lipid homeostasis.", "protein": "ABCG5", "relationship_type": "causal", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation required for ABCG8 function.", "mechanism": "ABCG8 downregulation impairs cholesterol efflux, contributing to dyslipidemia.", "protein": "ABCG8", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane. Plays an essential role in the selective transport of the dietary choles", "gene_name": "ABCG8", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9H221" }, "relationship_type": "causal", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Drug\u2013drug interactions", "glycan_involvement": "N-glycosylation modulates ABCB1 stability and substrate specificity.", "mechanism": "ABCB1 upregulation in postmenopausal state may alter drug absorption and resistance.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12227904" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "CYP1A2 downregulation in MetS, hypertension, and postmenopause may slow drug metabolism.", "protein": "CYP1A2", "protein_enriched": { "function": "", "gene_name": "10A19I.14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Not a glycoprotein.", "mechanism": "CYP2D1 upregulation in hypertension and hypertriglyceridemia may alter drug and neurotransmitter metabolism.", "protein": "CYP2D1", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, Pu", "gene_name": "CYP2C8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10632" }, "relationship_type": "biomarker", "source_pmcid": "PMC12227904" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates CRP's inflammatory activity.", "mechanism": "Elevated CRP is a risk factor and mediator for cardiovascular complications in MetS.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Postmenopausal metabolic syndrome", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Intestinal ABCG5 upregulation in postmenopausal rats may increase cholesterol secretion.", "protein": "ABCG5", "relationship_type": "biomarker", "source_pmcid": "PMC12227904" }, { "confidence": "medium", "disease": "Postmenopausal metabolic syndrome", "glycan_involvement": "N-glycosylation modulates function.", "mechanism": "Intestinal ABCB1 upregulation may affect drug absorption in postmenopausal state.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12227904" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "PROM1 is a transmembrane glycoprotein; glycosylation is essential for its cell surface localization and function.", "mechanism": "PROM1 is upregulated in DKD, promotes renal fibrosis, correlates with decreased renal function, and is associated with M2 macrophage infiltration and immunosuppressive microenvironment.", "protein": "PROM1 (CD133)", "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "THY1 is highly glycosylated; glycosylation is critical for its cell surface expression and function in cell signaling.", "mechanism": "THY1 is downregulated in DKD, exhibits protective effects against renal fibrosis, correlates with better renal function, and is associated with regulatory T cell infiltration.", "protein": "THY1 (CD90)", "relationship_type": "biomarker/therapeutic_target/protective", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation supports PROM1's stability and function in fibrosis.", "mechanism": "PROM1 promotes fibrosis progression via ECM remodeling and immune modulation.", "protein": "PROM1 (CD133)", "relationship_type": "causal", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation modulates THY1's interaction with fibroblasts and ECM.", "mechanism": "THY1 inhibits fibroblast activation and ECM deposition, reducing fibrosis.", "protein": "THY1 (CD90)", "relationship_type": "protective", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Chronic kidney failure", "glycan_involvement": "Glycosylation required for PROM1's pathological activity.", "mechanism": "PROM1 expression correlates with decreased GFR and increased serum creatinine.", "protein": "PROM1 (CD133)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Chronic kidney failure", "glycan_involvement": "Glycosylation maintains THY1's protective signaling.", "mechanism": "THY1 expression correlates with improved GFR and lower serum creatinine.", "protein": "THY1 (CD90)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12228302" }, { "confidence": "medium", "disease": "Lung fibrosis", "glycan_involvement": "Glycosylation supports PROM1's anti-inflammatory function.", "mechanism": "PROM1 suppresses alveolar macrophage proliferation and inflammation.", "protein": "PROM1 (CD133)", "relationship_type": "protective", "source_pmcid": "PMC12228302" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for PROM1's regulatory role.", "mechanism": "PROM1 mitigates liver injury-induced fibrosis by stabilizing SMAD7.", "protein": "PROM1 (CD133)", "relationship_type": "protective", "source_pmcid": "PMC12228302" }, { "confidence": "medium", "disease": "Biliary fibrosis", "glycan_involvement": "Glycosylation supports PROM1's pro-fibrotic activity.", "mechanism": "PROM1 promotes biliary fibrosis in biliary atresia.", "protein": "PROM1 (CD133)", "relationship_type": "causal", "source_pmcid": "PMC12228302" }, { "confidence": "medium", "disease": "Lung/Heart/Liver fibrosis", "glycan_involvement": "Glycosylation is essential for THY1's anti-fibrotic signaling.", "mechanism": "THY1 inhibits fibroblast activation and ECM deposition, reducing fibrosis in multiple organs.", "protein": "THY1 (CD90)", "relationship_type": "protective", "source_pmcid": "PMC12228302" }, { "confidence": "high", "disease": "Leptospirosis", "glycan_involvement": "IgM is heavily N-glycosylated, affecting its stability and immune recognition.", "mechanism": "IgM anti-Leptospira antibodies indicate acute infection and are detected by ELISA for diagnosis.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Leptospirosis", "glycan_involvement": "OMPs are glycosylated, influencing host immune evasion.", "mechanism": "OMPs mediate bacterial adhesion and invasion of host tissues.", "protein": "Leptospira outer membrane proteins (OMPs)", "relationship_type": "causal", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Leptospirosis", "glycan_involvement": "LPS contains glycan moieties critical for antigenicity.", "mechanism": "LPS triggers host immune response and inflammation.", "protein": "Leptospira lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation affects myoglobin clearance and toxicity.", "mechanism": "Released from damaged muscle, myoglobin is a marker for rhabdomyolysis.", "protein": "Myoglobin", "protein_enriched": { "function": "Monomeric heme protein which primary function is to store oxygen and facilitate its diffusion within muscle tissues. Reversibly binds oxygen through a pentacoordinated heme iron and enables its timely", "gene_name": "MB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "CPK glycosylation modulates enzyme activity and serum half-life.", "mechanism": "Elevated CPK indicates muscle breakdown in rhabdomyolysis.", "protein": "Creatine phosphokinase (CPK)", "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "LDH glycosylation influences enzyme stability.", "mechanism": "LDH is released during muscle injury and is elevated in rhabdomyolysis.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects AST secretion and activity.", "mechanism": "AST elevation reflects hepatic and muscle injury.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "ALT glycosylation impacts enzyme function.", "mechanism": "ALT is a marker for hepatocellular damage.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "ALP is highly glycosylated, affecting its activity and serum levels.", "mechanism": "ALP elevation is associated with cholestatic liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation of IgM modulates immune complex formation and renal deposition.", "mechanism": "IgM anti-Leptospira is used to diagnose leptospirosis-induced AKI.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12228305" }, { "confidence": "high", "disease": "Drug-induced adverse reactions", "glycan_involvement": "P-gp is a glycoprotein; glycosylation affects its trafficking and function.", "mechanism": "Inhibition of P-gp by danicopan increases exposure to P-gp substrates, raising risk of adverse drug reactions.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "high", "disease": "Drug-induced adverse reactions", "glycan_involvement": "BCRP glycosylation modulates its stability and drug transport activity.", "mechanism": "Inhibition of BCRP by danicopan increases exposure to BCRP substrates, raising risk of adverse drug reactions.", "protein": "Breast Cancer Resistance Protein (BCRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "medium", "disease": "Drug-induced adverse reactions", "glycan_involvement": "OATP1B1 is glycosylated; glycosylation affects membrane localization.", "mechanism": "Trofinetide inhibits OATP1B1 in vitro, potentially altering hepatic drug uptake and increasing risk of adverse reactions.", "protein": "OATP1B1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "medium", "disease": "Drug-induced adverse reactions", "glycan_involvement": "OATP1B3 glycosylation impacts function.", "mechanism": "Trofinetide and rezafungin inhibit OATP1B3 in vitro, potentially altering drug disposition.", "protein": "OATP1B3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "high", "disease": "Drug resistance", "glycan_involvement": "Glycosylation is essential for P-gp stability and drug efflux activity.", "mechanism": "P-gp overexpression leads to multidrug resistance in various diseases.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12239508" }, { "confidence": "high", "disease": "Drug resistance", "glycan_involvement": "Glycosylation modulates BCRP function.", "mechanism": "BCRP overexpression causes resistance to chemotherapeutics.", "protein": "BCRP", "relationship_type": "causal", "source_pmcid": "PMC12239508" }, { "confidence": "medium", "disease": "Drug-induced adverse reactions", "glycan_involvement": "CYP3A4 is glycosylated; glycosylation affects enzyme stability.", "mechanism": "Inhibition or induction of CYP3A4 by peptide drugs can alter metabolism of co-administered drugs.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "medium", "disease": "Drug-induced adverse reactions", "glycan_involvement": "UGT1A9 is glycosylated; glycosylation affects enzyme activity.", "mechanism": "Trofinetide inhibits UGT1A9 in vitro, potentially affecting drug glucuronidation.", "protein": "UGT1A9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "medium", "disease": "Drug-induced adverse reactions", "glycan_involvement": "UGT2B7 glycosylation modulates function.", "mechanism": "Trofinetide inhibits UGT2B7 in vitro, potentially affecting drug glucuronidation.", "protein": "UGT2B7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "low", "disease": "Drug-induced adverse reactions", "glycan_involvement": "MATE1 is glycosylated; glycosylation affects transporter function.", "mechanism": "Rezafungin inhibits MATE1 in vitro, potentially altering renal drug excretion.", "protein": "MATE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12239508" }, { "confidence": "high", "disease": "Nephrogenic Diabetes Insipidus", "glycan_involvement": "AQP2 glycosylation affects its trafficking and stability; altered glycosylation may exacerbate NDI.", "mechanism": "Lithium downregulates AQP2 expression in renal collecting ducts, impairing water reabsorption.", "protein": "Aquaporin-2", "protein_enriched": { "function": "Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (Pu", "gene_name": "AQP2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P41181" }, "relationship_type": "causal", "source_pmcid": "PMC12260583" }, { "confidence": "medium", "disease": "Acute Kidney Injury", "glycan_involvement": "Glycosylation status influences AQP2 excretion and detection.", "mechanism": "Reduced AQP2 in urine reflects collecting duct dysfunction in AKI.", "protein": "Aquaporin-2", "protein_enriched": { "function": "Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (Pu", "gene_name": "AQP2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P41181" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260583" }, { "confidence": "medium", "disease": "Anaemia", "glycan_involvement": "EPO glycosylation is essential for stability and activity.", "mechanism": "Renal injury impairs EPO glycoprotein production, leading to anaemia.", "protein": "Erythropoietin", "relationship_type": "causal", "source_pmcid": "PMC12260583" }, { "confidence": "low", "disease": "Anaemia", "glycan_involvement": "Altered glycosylation affects transferrin function and diagnostic value.", "mechanism": "Transferrin glycoprotein levels reflect iron transport and anaemia status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12260583" }, { "confidence": "low", "disease": "Lithium Toxicity", "glycan_involvement": "AST is glycosylated; changes may affect serum levels.", "mechanism": "Elevated AST indicates systemic toxicity and possible hepatic involvement.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12260583" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation regulates cell\u2013cell recognition and adhesion.", "mechanism": "Essential for myoblast fusion; impaired function disrupts muscle regeneration in ALS.", "protein": "M-cadherin (M-cad)", "protein_enriched": { "function": "Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1. May play a role in the atherosclerotic process such as clearing lipoproteins from plaques and in phagocytosis of blood-borne pathogens, parti", "gene_name": "ITGAD", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q13349" }, "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Heparan sulfate glycosylation critical for synaptic signaling.", "mechanism": "Coordinates NMJ stability via LRP4-MuSK signaling; disruption leads to NMJ degeneration in ALS.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation modulates integrin-ligand interactions.", "mechanism": "Mediates myoblast adhesion and differentiation; altered signaling impairs muscle regeneration.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation affects ECM assembly and cell signaling.", "mechanism": "Secreted during myogenesis; altered expression affects myogenic differentiation in ALS.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Receptor for agrin; disruption impairs NMJ maintenance and muscle innervation.", "protein": "LRP4", "protein_enriched": { "function": "Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neu", "gene_name": "LRP4", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G80920RR", "G08918WF", "G57321FI", "G75162EY", "G43417UB", "G49108TO", "G70696MD" ], "uniprot_id": "O75096" }, "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation modulates receptor activity.", "mechanism": "Agrin-LRP4-MuSK pathway maintains NMJ; dysfunction leads to synaptic instability in ALS.", "protein": "MuSK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation required for receptor clustering and function.", "mechanism": "Fragmentation/misclustering at NMJ reflects postsynaptic destabilization in ALS.", "protein": "Nicotinic acetylcholine receptor (nAChR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "N-glycosylation regulates adhesive properties.", "mechanism": "Mediate cell\u2013cell adhesion during myogenesis; altered function impairs muscle repair.", "protein": "Cadherins (general)", "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation modulates cell\u2013cell interactions.", "mechanism": "Involved in myoblast recognition and fusion; dysfunction contributes to impaired regeneration.", "protein": "Cell adhesion molecules (CAMs)", "relationship_type": "causal", "source_pmcid": "PMC12266013" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "Glycosylation affects membrane association and stability.", "mechanism": "Mis-expression/structural alteration in ALS muscle biopsies; contributes to fiber instability.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "biomarker", "source_pmcid": "PMC12266013" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect stability and trafficking.", "mechanism": "High ferritin in olfactory ensheathing cells (OECs) correlates with iron accumulation and neuroinflammation markers (lipofuscin, activated microglia).", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "high", "disease": "Neurodegeneration", "glycan_involvement": "Glycosylation may modulate ferritin turnover and cellular localization.", "mechanism": "Elevated ferritin and iron in OECs are associated with neurodegenerative processes, possibly due to phagocytosis of axonal debris.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "CD68 is heavily glycosylated; glycosylation affects lysosomal targeting and function.", "mechanism": "CD68+ activated microglia accumulate near high iron regions, indicating inflammatory response.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Ferritin glycosylation may influence aggregation and iron storage.", "mechanism": "Increased ferritin and iron in substantia nigra neurons detected by T2* MRI in PD patients.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation may affect ferritin stability in disease context.", "mechanism": "Elevated ferritin and iron accompany amyloid \u03b2 aggregation in AD hippocampus.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis (ALS)", "glycan_involvement": "Glycosylation may modulate ferritin uptake by phagocytes.", "mechanism": "Iron-laden activated microglia and macrophages with high ferritin found in ALS brain.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may affect ferritin clearance and immune recognition.", "mechanism": "Iron-laden activated microglia/macrophages with high ferritin observed in MS lesions.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "low", "disease": "Neurodegeneration", "glycan_involvement": "SV2 is glycosylated; glycosylation affects synaptic vesicle trafficking.", "mechanism": "SV2 used as control in EM; synaptic vesicle glycoproteins may be altered in neurodegeneration.", "protein": "SV2", "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Glycosylation regulates CD68 function in phagocytosis.", "mechanism": "CD68+ microglia activation is associated with axonal degeneration and lipofuscin accumulation.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12327075" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may modulate ferritin's protective role against iron-induced oxidative stress.", "mechanism": "High ferritin/iron may promote reactive oxygen species and lipofuscin formation, driving inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "causal", "source_pmcid": "PMC12327075" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its clearance and receptor binding.", "mechanism": "Elevated LDL is atherogenic, promoting plaque formation in arteries.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12329371" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates LDL's interaction with arterial proteoglycans.", "mechanism": "LDL accumulation in arterial walls leads to plaque development.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12329371" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "HDL glycosylation influences its anti-atherogenic properties.", "mechanism": "HDL promotes reverse cholesterol transport, reducing CVD risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12329371" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation affects ApoB-100 folding and LDL assembly.", "mechanism": "ApoB-100 is the main protein of LDL; its levels reflect LDL particle number.", "protein": "Apolipoprotein B-100", "relationship_type": "biomarker", "source_pmcid": "PMC12329371" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ApoB-100's interaction with arterial matrix.", "mechanism": "ApoB-100-containing particles are retained in arterial walls, initiating atherogenesis.", "protein": "Apolipoprotein B-100", "relationship_type": "causal", "source_pmcid": "PMC12329371" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "O-glycosylation affects ApoA-I stability and HDL function.", "mechanism": "ApoA-I is the main protein of HDL, mediating cholesterol efflux.", "protein": "Apolipoprotein A-I", "relationship_type": "protective", "source_pmcid": "PMC12329371" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Altered N-glycosylation increases LDL atherogenicity.", "mechanism": "LDL glycosylation affects its uptake and retention in arterial walls, promoting plaque formation.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12331343" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation at specific sites enhances LDL retention.", "mechanism": "Glycosylation of ApoB-100 modulates LDL particle stability and interaction with arterial proteoglycans.", "protein": "Apolipoprotein B-100", "relationship_type": "causal", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "N-glycosylation modulates ICAM-1 function.", "mechanism": "ICAM-1 glycosylation regulates leukocyte adhesion and transmigration during vascular inflammation.", "protein": "Intercellular Adhesion Molecule 1 (ICAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "VCAM-1 glycosylation facilitates monocyte recruitment to endothelium.", "protein": "Vascular Cell Adhesion Molecule 1 (VCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Acute Coronary Syndrome", "glycan_involvement": "Sialylated O-glycans essential for selectin function.", "mechanism": "E-selectin glycosylation mediates leukocyte rolling and vascular inflammation.", "protein": "Selectins (E-selectin)", "relationship_type": "biomarker", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates receptor activity.", "mechanism": "CD36 glycosylation affects uptake of oxidized LDL by macrophages, promoting foam cell formation.", "protein": "Cluster of Differentiation 36 (CD36)", "relationship_type": "causal", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Plaque Rupture", "glycan_involvement": "N-glycosylation influences ligand affinity.", "mechanism": "LOX-1 glycosylation regulates binding and uptake of oxidized LDL, contributing to plaque instability.", "protein": "Lectin-like oxidized LDL receptor 1 (LOX-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Altered Fc N-glycosylation affects immune cell activation.", "mechanism": "IgG Fc glycosylation modulates inflammatory response in atherosclerotic lesions.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Plaque Rupture", "glycan_involvement": "N-glycosylation impacts secretion and stability.", "mechanism": "MMP-9 glycosylation regulates enzyme activity and extracellular matrix degradation.", "protein": "Matrix Metalloproteinase 9 (MMP-9)", "relationship_type": "causal", "source_pmcid": "PMC12331343" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation influences antigenicity.", "mechanism": "CD68 glycosylation marks macrophage infiltration in plaques.", "protein": "Cluster of Differentiation 68 (CD68)", "relationship_type": "biomarker", "source_pmcid": "PMC12331343" }, { "confidence": "medium", "disease": "Hormonal imbalance (female)", "glycan_involvement": "SHBG is a glycoprotein; glycosylation affects its stability and hormone-binding capacity.", "mechanism": "SHBG regulates bioavailability of testosterone; altered SHBG levels may reflect or contribute to hormonal imbalance.", "protein": "Sex hormone-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12331471" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome", "glycan_involvement": "Glycosylation modulates SHBG function and serum levels.", "mechanism": "Altered SHBG levels influence free testosterone, relevant in PCOS pathophysiology.", "protein": "Sex hormone-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12331471" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may affect SHBG clearance and function.", "mechanism": "Low SHBG is associated with insulin resistance and metabolic syndrome.", "protein": "Sex hormone-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12331471" }, { "confidence": "medium", "disease": "Aromatase inhibitor-associated musculoskeletal syndrome (AIMSS)", "glycan_involvement": "OC is a glycoprotein; glycosylation affects its stability and function in bone metabolism.", "mechanism": "OC levels reflect bone turnover and are monitored in AIMSS patients to assess bone metabolism.", "protein": "Osteocalcin (OC)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "medium", "disease": "Aromatase inhibitor-associated musculoskeletal syndrome (AIMSS)", "glycan_involvement": "\u03b2-CTX is a glycopeptide fragment; glycosylation may affect its detection and clearance.", "mechanism": "\u03b2-CTX is a marker of bone resorption, elevated in increased bone turnover seen in AIMSS.", "protein": "Beta C-terminal telopeptide of type I collagen (\u03b2-CTX)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates OC's half-life and activity.", "mechanism": "OC is used to monitor bone formation and turnover in osteoporosis, which is a risk in AI-treated patients.", "protein": "Osteocalcin (OC)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation status may influence \u03b2-CTX immunoreactivity.", "mechanism": "\u03b2-CTX is elevated in osteoporosis due to increased bone resorption.", "protein": "Beta C-terminal telopeptide of type I collagen (\u03b2-CTX)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "low", "disease": "Bone loss", "glycan_involvement": "GH is a glycoprotein; glycosylation is essential for its secretion and receptor interaction.", "mechanism": "GH promotes bone formation; increased GH may counteract bone loss in AI+OFS patients.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "protective", "source_pmcid": "PMC12331576" }, { "confidence": "medium", "disease": "Bone loss", "glycan_involvement": "Glycosylation affects OC's stability in circulation.", "mechanism": "Decreased OC indicates reduced bone formation in bone loss conditions.", "protein": "Osteocalcin (OC)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "medium", "disease": "Bone loss", "glycan_involvement": "Glycosylation may affect \u03b2-CTX's immunodetection.", "mechanism": "Increased \u03b2-CTX reflects enhanced bone resorption in bone loss.", "protein": "Beta C-terminal telopeptide of type I collagen (\u03b2-CTX)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Glycosylation influences OC's function in bone metabolism.", "mechanism": "OC is monitored in breast cancer patients on AIs to assess bone health.", "protein": "Osteocalcin (OC)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect \u03b2-CTX's clearance.", "mechanism": "\u03b2-CTX is used to monitor bone resorption in breast cancer patients receiving AIs.", "protein": "Beta C-terminal telopeptide of type I collagen (\u03b2-CTX)", "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "low", "disease": "Aromatase inhibitor-associated musculoskeletal syndrome (AIMSS)", "glycan_involvement": "GH glycosylation is required for its biological activity.", "mechanism": "GH levels may increase in AI+OFS patients, potentially reflecting compensatory bone metabolism.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331576" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "BSP interacts with glycosylated regions of \u03b1-amylase, affecting its activity.", "mechanism": "Bletilla striata polysaccharide (BSP) inhibits \u03b1-amylase, reducing starch breakdown and glucose absorption.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331579" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "BSP binds to glycosylated domains, modulating enzyme activity.", "mechanism": "BSP competitively inhibits \u03b1-glucosidase, decreasing oligosaccharide hydrolysis and intestinal glucose uptake.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331579" }, { "confidence": "high", "disease": "Postprandial hyperglycemia", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "\u03b1-amylase activity increases glucose release from dietary starch, contributing to postprandial hyperglycemia.", "protein": "\u03b1-amylase", "relationship_type": "causal", "source_pmcid": "PMC12331579" }, { "confidence": "high", "disease": "Postprandial hyperglycemia", "glycan_involvement": "Glycosylation modulates substrate specificity and activity.", "mechanism": "\u03b1-glucosidase hydrolyzes oligosaccharides to glucose, raising blood sugar after meals.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "causal", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Polysaccharide binding to glycosylated sites reduces enzyme function.", "mechanism": "Inhibition of \u03b1-amylase by BSP lowers postprandial glucose spikes, offering protective effects.", "protein": "\u03b1-amylase", "relationship_type": "protective", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Competitive inhibition at glycosylated active sites.", "mechanism": "BSP inhibition of \u03b1-glucosidase reduces glucose absorption, protecting against hyperglycemia.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "protective", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation status may influence biomarker reliability.", "mechanism": "Elevated \u03b1-amylase activity is associated with increased risk of diabetes.", "protein": "\u03b1-amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation affects enzyme activity and detection.", "mechanism": "\u03b1-glucosidase activity correlates with glucose metabolism and diabetes risk.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Postprandial hyperglycemia", "glycan_involvement": "BSP interacts with glycosylated regions to inhibit function.", "mechanism": "Targeting \u03b1-amylase with BSP reduces post-meal glucose excursions.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331579" }, { "confidence": "medium", "disease": "Postprandial hyperglycemia", "glycan_involvement": "Competitive binding at glycosylated active sites.", "mechanism": "BSP inhibition of \u03b1-glucosidase lowers postprandial glucose levels.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331579" }, { "confidence": "high", "disease": "PIRRA", "glycan_involvement": "GPI-anchor and glycosylation required for membrane localization and receptor function.", "mechanism": "Upregulated in synovial tissue, forms receptor clusters with Tlr2, initiates sustained inflammatory signaling via PI3K-AKT pathway.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "high", "disease": "PIRRA", "glycan_involvement": "Glycosylation affects secretion and enzymatic activity.", "mechanism": "Upregulated; catalyzes LPA production, activates PI3K-AKT signaling, promotes synovial cell migration and inflammation.", "protein": "Enpp2", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:15837923, PubMed:17609370", "gene_name": "Angptl4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9Z1P8" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12331588" }, { "confidence": "high", "disease": "PIRRA", "glycan_involvement": "N-glycosylation required for proper folding and cell surface expression.", "mechanism": "Upregulated; forms complexes with CD14, triggers inflammatory cascades targeting Golgi apparatus and PI3K-AKT pathway.", "protein": "Tlr2", "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "high", "disease": "PIRRA", "glycan_involvement": "Glycosylation influences secretion and stability.", "mechanism": "Upregulated; secreted via Golgi vesicles, contributes to inflammation and immune modulation.", "protein": "Lyz2", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents", "gene_name": "LYZ", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61626" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "high", "disease": "PIRRA", "glycan_involvement": "Golgi processing (potential glycosylation) required for maturation and secretion.", "mechanism": "Upregulated; processed in Golgi, involved in immune effector functions and inflammation.", "protein": "Mpeg1", "protein_enriched": { "function": "Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including t", "gene_name": "Ifih1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8R5F7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "Glycosylation impacts secretion and function.", "mechanism": "Elevated in RA synovium; modulates inflammatory response via LPA signaling.", "protein": "Enpp2", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:15837923, PubMed:17609370", "gene_name": "Angptl4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9Z1P8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "Glycosylation required for receptor activity.", "mechanism": "Highly expressed in RA synovial fibroblasts; promotes migration and cartilage degradation.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Highly expressed in RA synovial fibroblasts; triggers inflammatory signaling.", "protein": "Tlr2", "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "Glycosylation affects secretion.", "mechanism": "Elevated in RA synovial fluid; contributes to inflammation.", "protein": "Lyz2", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents", "gene_name": "LYZ", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P61626" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "Golgi processing (potential glycosylation) required for function.", "mechanism": "Inducible in RA synovial fibroblasts; involved in immune response.", "protein": "Mpeg1", "protein_enriched": { "function": "Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including t", "gene_name": "Ifih1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8R5F7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331588" }, { "confidence": "high", "disease": "ACS", "glycan_involvement": "HDL particles contain glycosylated apolipoproteins (e.g., apoA1) affecting function.", "mechanism": "Higher HDL-C levels reduce mortality risk via enhanced cholesterol efflux and anti-inflammatory/antioxidant activity.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12331594" }, { "confidence": "medium", "disease": "ACS", "glycan_involvement": "LDL particles contain glycosylated apoB; glycosylation modulates uptake and immune response.", "mechanism": "Lower LDL-C levels observed in deceased ACS patients; role as risk marker is complex.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "TGRL surface glycoproteins mediate cell interactions and uptake.", "mechanism": "TGRL remnants internalized by macrophages form foam cells, driving plaque formation and rupture.", "protein": "TGRL", "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Plaque Rupture", "glycan_involvement": "N-glycosylation of apoB affects lipoprotein structure and atherogenicity.", "mechanism": "apoB-containing lipoproteins accumulate in vessel walls, promoting foam cell formation and plaque instability.", "protein": "apoB", "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "medium", "disease": "ACS", "glycan_involvement": "Glycosylation modulates apoA1 stability and function.", "mechanism": "apoA1 in HDL facilitates cholesterol efflux and anti-inflammatory effects, lowering ACS risk.", "protein": "apoA1", "relationship_type": "protective", "source_pmcid": "PMC12331594" }, { "confidence": "medium", "disease": "AMI", "glycan_involvement": "N-glycosylation required for GLUT1 trafficking and function.", "mechanism": "Upregulation of GLUT1 enhances glucose transport to immune cells, modulating immune response in AMI.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Platelet surface glycoproteins (e.g., GPIIb/IIIa) mediate aggregation; glycosylation affects function.", "mechanism": "Platelet activation contributes to thrombosis and microcirculatory disturbances in ACS/AMI.", "protein": "Platelet", "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Neutrophil glycoproteins (e.g., selectins) regulate migration and activation.", "mechanism": "Activated neutrophils release pro-inflammatory factors and ROS, exacerbating myocardial injury and heart failure.", "protein": "Neutrophil", "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Monocyte surface glycoproteins mediate adhesion and transmigration.", "mechanism": "Monocyte infiltration and foam cell formation drive atherosclerotic progression.", "protein": "Monocyte", "relationship_type": "causal", "source_pmcid": "PMC12331594" }, { "confidence": "medium", "disease": "ACS", "glycan_involvement": "S1P signaling is modulated by glycosylated receptors.", "mechanism": "S1P promotes inflammation resolution and may counteract lipid-induced injury.", "protein": "Sphingosine-1-phosphate (S1P)", "relationship_type": "protective", "source_pmcid": "PMC12331594" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "GLUT3 is N-glycosylated, which is essential for its membrane localization and glucose transport activity.", "mechanism": "GLUT3 promotes glycolytic metabolism and proliferation in NSCLC; BAG5 maintains GLUT3 protein levels via post-transcriptional regulation.", "protein": "GLUT3", "protein_enriched": { "function": "Facilitative glucose transporter (PubMed:26176916, PubMed:32860739, PubMed:9477959). Can also mediate the uptake of various other monosaccharides across the cell membrane (PubMed:26176916, PubMed:9477", "gene_name": "SLC2A3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11169" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "No direct glycosylation; acts via glycoprotein partners.", "mechanism": "BAG5 promotes NSCLC proliferation, invasion, EMT, and metabolic reprogramming by regulating translation and mitochondrial dynamics.", "protein": "BAG5", "protein_enriched": { "function": "Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding (PubMed:20223214). Has an", "gene_name": "BAG5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UL15" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12331601" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may affect IGF2BP1 stability and RNA-binding.", "mechanism": "IGF2BP1 interacts with BAG5 to regulate mRNA stability and translation of oncogenic transcripts, supporting NSCLC progression.", "protein": "IGF2BP1", "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may modulate function.", "mechanism": "IGF2BP2 is part of BAG5 interactome, regulating translation of metabolic and EMT-related genes.", "protein": "IGF2BP2", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6M1" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation may affect RNA-binding and stability.", "mechanism": "IGF2BP3 interacts with BAG5, promoting translation of glycolytic and EMT effectors.", "protein": "IGF2BP3", "protein_enriched": { "function": "RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the", "gene_name": "IGF2BP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9NZI8" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation modulates \u03b2-catenin stability and signaling.", "mechanism": "BAG5 upregulates \u03b2-catenin, driving Wnt signaling, stemness, and EMT in NSCLC.", "protein": "CTNNB1 (\u03b2-catenin)", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:15132997). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-t", "gene_name": "Ctnnb1", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G36379GD", "G62765YT" ], "uniprot_id": "Q02248" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation is critical for E-cadherin-mediated cell adhesion.", "mechanism": "BAG5 knockout increases E-cadherin, suppressing EMT and invasion.", "protein": "CDH1 (E-cadherin)", "relationship_type": "protective", "source_pmcid": "PMC12331601" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation affects N-cadherin function in cell migration.", "mechanism": "BAG5 promotes N-cadherin expression, facilitating EMT and metastasis.", "protein": "CDH2 (N-cadherin)", "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation required for GLUT3 function.", "mechanism": "GLUT3 is transcriptionally activated by YY1, promoting glycolysis and tumor growth.", "protein": "GLUT3", "protein_enriched": { "function": "Facilitative glucose transporter (PubMed:26176916, PubMed:32860739, PubMed:9477959). Can also mediate the uptake of various other monosaccharides across the cell membrane (PubMed:26176916, PubMed:9477", "gene_name": "SLC2A3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11169" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "No direct glycosylation.", "mechanism": "BAG5 promotes proliferation and invasion; targeted by miR-127 as a tumor suppressor.", "protein": "BAG5", "protein_enriched": { "function": "Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding (PubMed:20223214). Has an", "gene_name": "BAG5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UL15" }, "relationship_type": "causal", "source_pmcid": "PMC12331601" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "MDK is a heparin-binding glycoprotein; glycosylation facilitates its interaction with LRP1 and ECM components.", "mechanism": "MDK acts as a ligand for LRP1, mediating intercellular communication between C2 PCLAF+ glioma cells and fibroblasts, promoting tumor progression and immunosuppressive microenvironment.", "protein": "MDK", "protein_enriched": { "function": "Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:2", "gene_name": "MTR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99707" }, "relationship_type": "causal", "source_pmcid": "PMC12331606" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "LRP1 is heavily N-glycosylated, which is essential for ligand binding and receptor trafficking.", "mechanism": "LRP1 acts as a receptor for MDK, enabling fibroblast response to glioma-derived signals, supporting tumor growth and immune evasion.", "protein": "LRP1", "relationship_type": "causal", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation modulates CHI3L1 stability and ECM interactions.", "mechanism": "CHI3L1 is a marker for the C0 glioma subtype, associated with hypoxia response and ECM remodeling.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "PTN glycosylation enhances its binding to cell surface receptors and ECM.", "mechanism": "PTN is involved in glioma cell communication and proliferation, especially in the C2 PCLAF+ subtype.", "protein": "PTN", "relationship_type": "causal", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Potential O-glycosylation may regulate nuclear localization and function.", "mechanism": "PCNA is a marker for the C2 PCLAF+ subtype, indicating high proliferative activity.", "protein": "PCNA", "protein_enriched": { "function": "Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand (P", "gene_name": "PCNA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G03238UC" ], "uniprot_id": "P12004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Possible glycosylation may affect protein-protein interactions in the nucleus.", "mechanism": "PCLAF is highly expressed in the C2 PCLAF+ subtype, driving DNA replication and cell cycle progression.", "protein": "PCLAF", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may stabilize BIRC5 and modulate apoptosis inhibition.", "mechanism": "BIRC5 marks the C3 glioma subtype, associated with resistance to cell death and mitotic activity.", "protein": "BIRC5", "relationship_type": "biomarker", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may regulate NDRG1 function in metabolic adaptation.", "mechanism": "NDRG1 is a marker for the C4 glioma subtype, linked to glycolytic metabolism and adaptation to hypoxia.", "protein": "NDRG1", "relationship_type": "biomarker", "source_pmcid": "PMC12331606" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Membrane glycosylation affects TYROBP signaling and immune interactions.", "mechanism": "TYROBP marks the C5 glioma subtype, associated with immune cell activation and chemotaxis.", "protein": "TYROBP", "relationship_type": "biomarker", "source_pmcid": "PMC12331606" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Potential nuclear glycosylation may regulate transcriptional activity.", "mechanism": "YEATS4 is a key transcription factor in the C2 PCLAF+ subtype; its knockdown inhibits proliferation, migration, and invasion of GBM cells.", "protein": "YEATS4", "protein_enriched": { "function": "Replication termination factor which is a component of the elongating replisome (Probable). Required for ATR pathway signaling upon DNA damage and has a positive activity during DNA replication. Might", "gene_name": "RTF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BY42" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331606" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "CD226 is a glycoprotein; glycosylation may affect its cell surface expression and signaling.", "mechanism": "Upregulated on B cells, correlates with disease activity, drives B cell activation, autoantibody production, and pro-inflammatory cytokine secretion.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may regulate CD226 function on B cells.", "mechanism": "Elevated CD226+ B cells associated with increased disease activity and poor prognosis.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Idiopathic inflammatory myopathy (IIM)", "glycan_involvement": "Glycosylation may modulate tissue infiltration.", "mechanism": "CD226+ cells in muscle tissue correlate with severity of inflammation.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "causal", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "Glycosylation may influence receptor-ligand interactions.", "mechanism": "CD226+ T cells show enhanced pro-inflammatory activity; blockade reduces effector function.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Primary antiphospholipid syndrome", "glycan_involvement": "Glycosylation may affect NK cell activation.", "mechanism": "Upregulated on NK cells; associated with increased activation and IFN-\u03b3 production.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Tuberculosis (TB)", "glycan_involvement": "Glycosylation may regulate immune cell cytotoxicity.", "mechanism": "Elevated CD226+ T/NK cells produce more IFN-\u03b3; predictive of disease progression.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "low", "disease": "Acute myeloid leukemia", "glycan_involvement": "Glycosylation may affect cell adhesion and signaling.", "mechanism": "CD226+ B cells enriched in pathways linked to leukemia.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "low", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may modulate tumor microenvironment interactions.", "mechanism": "CD226+ B cells enriched in cancer-related pathways.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Epstein-Barr virus infection", "glycan_involvement": "Glycosylation may affect viral receptor interactions.", "mechanism": "EBV infection upregulates CD226 on B cells, promoting activation and differentiation.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "causal", "source_pmcid": "PMC12331654" }, { "confidence": "medium", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "Glycosylation may regulate costimulatory signaling.", "mechanism": "CD226 implicated in B cell activation and pro-inflammatory response.", "protein": "CD226", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cel", "gene_name": "CD226", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02815KT" ], "uniprot_id": "Q15762" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331654" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation affects processing and A\u03b2 production.", "mechanism": "APP is cleaved to produce A\u03b2 peptides, which aggregate to form plaques.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12331659" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 derives from glycosylated APP; glycosylation state influences aggregation.", "mechanism": "A\u03b2 aggregates extracellularly to form plaques, a hallmark of AD pathology.", "protein": "Beta-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12331659" }, { "confidence": "high", "disease": "Cerebral amyloid angiopathy (CAA)", "glycan_involvement": "Originates from glycosylated APP; glycosylation may affect vascular deposition.", "mechanism": "A\u03b240 deposits in cerebral vessels, causing vascular dysfunction.", "protein": "Beta-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "MOG is a glycoprotein; glycosylation is essential for its function and antigenicity.", "mechanism": "AD plasma enhances formation of MOG+ dots along nerve fibers.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Laminin is heavily glycosylated; glycosylation mediates cell adhesion and migration.", "mechanism": "AD plasma increases migration of laminin+/lectin+ endothelial cells.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Basigin is N-glycosylated; glycosylation regulates its cell surface expression.", "mechanism": "Identified as a modulator of endothelial cell migration in AD plasma.", "protein": "Basigin (CD147)", "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CRP is glycosylated; glycosylation affects its immune function.", "mechanism": "AD plasma modulates CRP, affecting microglial migration and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation is critical for ligand binding and complement activation.", "mechanism": "Implicated in inhibition of microglial migration by AD plasma.", "protein": "Mannose-binding protein C", "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates complement regulation.", "mechanism": "Involved in microglial response modulation in AD plasma.", "protein": "Complement factor H-related protein-3", "protein_enriched": { "function": "Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH", "gene_name": "CFHR5", "glycan_count": 24, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G10486CT", "G24954UD", "G45395BF", "G59626AS", "G95865ZB", "G29068FM", "G43417UB", "G00273SJ", "G06356OH", "G08290VR", "G08918WF", "G10846ZT", "G31986NC", "G40574BA", "G41071NU", "G43223CG", "G48414YA", "G49018RC", "G49642SA", "G70619PT", "G72747WU", "G84225JN", "G86182NS" ], "uniprot_id": "Q9BXR6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect filament assembly.", "mechanism": "Astroglial activation around plaques; GFAP upregulated in AD.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331659" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "ZO-1 is a glycoprotein; glycosylation is important for its stability and localization at tight junctions.", "mechanism": "ZO-1 maintains tight junctions, reducing intestinal permeability and endotoxin translocation.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12331688" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Occludin is a glycoprotein; glycosylation affects its function in tight junctions.", "mechanism": "Occludin supports tight junction integrity, preventing LPS leakage and inflammation.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12331688" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation of ZO-1 supports its barrier function.", "mechanism": "Upregulation of ZO-1 by Sch B restores gut barrier, reducing LPS-induced liver inflammation in MAFLD.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12331688" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Glycosylation is required for Occludin's membrane localization and function.", "mechanism": "Increased Occludin expression improves gut barrier, limiting progression of MAFLD.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12331688" }, { "confidence": "high", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Activation of PPAR\u03b3 by Sch B regulates lipid metabolism, reducing hepatic steatosis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331688" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulation of Plin2 promotes lipid droplet formation and fat storage, contributing to obesity.", "protein": "Plin2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12331688" }, { "confidence": "medium", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated Plin2 increases hepatic lipid accumulation in MAFLD.", "protein": "Plin2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12331688" }, { "confidence": "medium", "disease": "Liver steatosis", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Acsl4 upregulation enhances fatty acid activation, promoting hepatic steatosis.", "protein": "Acsl4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12331688" }, { "confidence": "medium", "disease": "Metabolic Associated Fatty Liver Disease (MAFLD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Fads1 upregulation by Sch B improves polyunsaturated fatty acid metabolism, reducing hepatic lipid content.", "protein": "Fads1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12331688" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Pck1 upregulation improves gluconeogenesis and energy metabolism, alleviating insulin resistance.", "protein": "Pck1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331688" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "DPP-4 is a heavily glycosylated transmembrane protein; glycosylation affects its enzymatic activity and cell surface localization.", "mechanism": "DPP-4 is upregulated in HCC, associated with tumor progression, immune modulation, and resistance to therapy; inhibition reduces preneoplastic changes.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12331699" }, { "confidence": "high", "disease": "Hepatic preneoplasia", "glycan_involvement": "Glycosylation required for DPP-4 stability and function.", "mechanism": "Elevated DPP-4 promotes preneoplastic lesions; inhibition by sitagliptin reduces lesion formation and inflammation.", "protein": "Dipeptidyl peptidase-4 (DPP-4)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12331699" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "GGT is glycosylated, which is essential for its enzymatic activity.", "mechanism": "GGT is elevated in liver injury and preneoplasia; reduction indicates hepatoprotection.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331699" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects CYP2E1 folding and stability.", "mechanism": "CYP2E1 bioactivates carcinogens (DEN), promoting DNA damage and carcinogenesis; inhibition reduces cancer risk.", "protein": "Cytochrome P450 2E1 (CYP2E1)", "relationship_type": "causal", "source_pmcid": "PMC12331699" }, { "confidence": "medium", "disease": "Hepatic preneoplasia", "glycan_involvement": "Glycosylation modulates CYP3A4 activity and membrane localization.", "mechanism": "CYP3A4 is suppressed in preneoplasia; restoration by sitagliptin may aid detoxification and reduce carcinogenesis.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "protective", "source_pmcid": "PMC12331699" }, { "confidence": "high", "disease": "Hepatic preneoplasia", "glycan_involvement": "GST-P glycosylation influences its stability and function.", "mechanism": "GST-P is highly expressed in preneoplastic lesions; reduction indicates chemopreventive effect.", "protein": "Placental glutathione S-transferase (GST-P)", "relationship_type": "biomarker", "source_pmcid": "PMC12331699" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect nuclear localization and function.", "mechanism": "PCNA marks cell proliferation; elevated in HCC and preneoplasia, reduced by sitagliptin.", "protein": "Proliferating cell nuclear antigen (PCNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12331699" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "Glycosylation can modulate NF-\u03baB signaling.", "mechanism": "NF-\u03baB drives inflammatory cytokine expression in preneoplasia and HCC; inhibition reduces inflammation and carcinogenesis.", "protein": "Nuclear factor kappa B (NF-\u03baB)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12331699" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Upregulation of BAX promotes apoptosis in cancer cells; sitagliptin increases BAX expression.", "protein": "BCL2-associated X protein (BAX)", "relationship_type": "protective", "source_pmcid": "PMC12331699" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation influences BCL2 function.", "mechanism": "BCL2 is anti-apoptotic; downregulation by sitagliptin promotes cancer cell death.", "protein": "B-cell lymphoma 2 (BCL2)", "relationship_type": "causal", "source_pmcid": "PMC12331699" }, { "confidence": "high", "disease": "Porcine Reproductive and Respiratory Syndrome (PRRS)", "glycan_involvement": "CD163 is a glycoprotein; glycosylation may affect receptor-virus interaction.", "mechanism": "Nanobodies block PRRSV entry by binding the SRCR5 domain of CD163, inhibiting viral attachment and replication.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "high", "disease": "African Swine Fever (ASF)", "glycan_involvement": "CD2v is a viral glycoprotein; glycosylation may influence antigenicity.", "mechanism": "Nanobodies targeting CD2v used in ELISA for ASFV detection.", "protein": "CD2v", "relationship_type": "biomarker", "source_pmcid": "PMC12331703" }, { "confidence": "high", "disease": "African Swine Fever (ASF)", "glycan_involvement": "p54 is glycosylated; glycan moieties may affect immune recognition.", "mechanism": "Nanobodies against p54 enable ASFV diagnosis and TRIM-away mediated protein degradation.", "protein": "p54", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "high", "disease": "African Swine Fever (ASF)", "glycan_involvement": "p72 is a glycoprotein; glycosylation impacts antigenicity.", "mechanism": "Nanobodies used for ASFV detection and targeted degradation.", "protein": "p72", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "high", "disease": "Avian Influenza", "glycan_involvement": "HA1 is heavily glycosylated; glycosylation modulates immune escape and antibody binding.", "mechanism": "Nanobodies bind conserved HA1 epitopes, neutralizing diverse IAV H5 clades.", "protein": "HA1 (Hemagglutinin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "ClfA is glycosylated; glycosylation may affect ligand binding.", "mechanism": "Nanobodies detect ClfA for S. aureus diagnosis.", "protein": "ClfA (Clumping factor A)", "protein_enriched": { "function": "Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate", "gene_name": "asd", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q53612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331703" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection", "glycan_involvement": "\u03b1-hemolysin is glycosylated; glycosylation may influence toxin activity.", "mechanism": "Nanobody-based ELISA detects \u03b1-hemolysin in food samples.", "protein": "\u03b1-hemolysin", "protein_enriched": { "function": "Alpha-toxin binds to the membrane of eukaryotic cells (particularly red blood cells, RBC) forming pores, resulting in hemolysis, with the release of low-molecular weight molecules leading to eventual ", "gene_name": "hly", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09616" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331703" }, { "confidence": "medium", "disease": "Anthrax", "glycan_involvement": "BclA is glycosylated; glycosylation affects spore surface properties.", "mechanism": "Nanobody-\u03b2-gal fusion detects BclA for sensitive anthrax diagnosis.", "protein": "BclA (Bacillus collagen-like protein)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q81ZP7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331703" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "ESAT-6 is not glycosylated; no direct glycan involvement.", "mechanism": "Nanobodies inhibit ESAT-6, reducing M. tuberculosis growth in macrophages.", "protein": "ESAT-6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "medium", "disease": "Trypanosomiasis", "glycan_involvement": "Tb BILBO1 is glycosylated; glycosylation may affect protein stability and immune recognition.", "mechanism": "Nanobodies targeting Tb BILBO1 disrupt trypanosome cytoskeleton, killing parasites.", "protein": "Tb BILBO1", "protein_enriched": { "function": "", "gene_name": "Tb07.5F10.300", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q57UQ3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331703" }, { "confidence": "high", "disease": "Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)", "glycan_involvement": "TRAP is a glycoprotein; glycosylation may affect stability and function, but not directly discussed.", "mechanism": "Loss-of-function mutations in ACP5 (TRAP) lead to dysregulation of OPN phosphorylation, excess phosphorylated OPN, and immune/bone abnormalities.", "protein": "Tartrate-resistant acid phosphatase (TRAP)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "high", "disease": "Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)", "glycan_involvement": "OPN is a secreted glycoprotein; glycosylation may modulate its immune and bone activities.", "mechanism": "Excess phosphorylated OPN (due to TRAP deficiency) promotes osteoclast activation (bone resorption) and type I interferon production (immune dysregulation).", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "medium", "disease": "Skeletal dysplasia", "glycan_involvement": "Glycosylation of OPN may affect its interaction with cells and matrix.", "mechanism": "Excess phosphorylated OPN enhances osteoclast activity, leading to abnormal bone resorption and skeletal dysplasia.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "medium", "disease": "Autoimmune hemolytic anemia", "glycan_involvement": "Glycosylation may influence OPN's immunomodulatory properties.", "mechanism": "OPN-driven type I interferon production promotes autoimmunity, contributing to hemolytic anemia.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "medium", "disease": "Immune thrombocytopenia", "glycan_involvement": "Glycosylation may affect OPN's immune signaling.", "mechanism": "OPN-induced immune activation leads to autoimmunity against platelets.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "high", "disease": "Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)", "glycan_involvement": "IFNAR1 is a glycoprotein; glycosylation is important for receptor function.", "mechanism": "Type I interferons signal via IFNAR1/2; JAK inhibitors (ruxolitinib, tofacitinib) block downstream signaling, reducing autoimmunity.", "protein": "IFNAR1", "protein_enriched": { "function": "Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2", "gene_name": "IFNAR1", "glycan_count": 13, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G22310AV", "G13694XX", "G81263BG", "G25079LO", "G06356OH", "G33791AF", "G86795LJ", "G62765YT", "G75983OB", "G04657PL", "G41071NU", "G93656SY", "G80920RR" ], "uniprot_id": "P17181" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331710" }, { "confidence": "high", "disease": "Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)", "glycan_involvement": "IFNAR2 glycosylation is required for proper receptor function.", "mechanism": "Type I interferon signaling via IFNAR2 is implicated in disease; JAK inhibitors modulate this pathway.", "protein": "IFNAR2", "protein_enriched": { "function": "Together with IFNAR1, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:10556041, PubMed:21854986, PubMed:2", "gene_name": "IFNAR2", "glycan_count": 9, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G40926MX", "G47518TP", "G48414YA", "G59536GA", "G59626AS", "G62765YT" ], "uniprot_id": "P48551" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331710" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation may modulate OPN's immune effects.", "mechanism": "OPN overactivity (via type I IFN) is associated with SLE-like autoimmunity in SPENCDI.", "protein": "Osteopontin (OPN)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331710" }, { "confidence": "low", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect OPN's inflammatory properties.", "mechanism": "OPN-driven immune activation may contribute to RA-like features in SPENCDI.", "protein": "Osteopontin (OPN)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331710" }, { "confidence": "low", "disease": "Intracranial calcification", "glycan_involvement": "TRAP glycosylation may affect enzyme stability; not directly discussed.", "mechanism": "TRAP deficiency leads to immune dysregulation and abnormal calcification in the CNS.", "protein": "Tartrate-resistant acid phosphatase (TRAP)", "relationship_type": "causal", "source_pmcid": "PMC12331710" }, { "confidence": "high", "disease": "graft rejection", "glycan_involvement": "Glycosylation is essential for antibody stability and function.", "mechanism": "Basiliximab, a glycosylated monoclonal antibody, blocks IL-2 receptor on T cells, reducing immune activation.", "protein": "basiliximab (Simulect)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331733" }, { "confidence": "high", "disease": "renal anemia", "glycan_involvement": "N-glycosylation required for receptor binding and in vivo activity.", "mechanism": "Recombinant erythropoietin, a glycoprotein, stimulates erythropoiesis in patients with renal anemia.", "protein": "erythropoietin stimulating agent", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331733" }, { "confidence": "high", "disease": "graft rejection", "glycan_involvement": "HLA glycosylation affects antigen presentation and immune recognition.", "mechanism": "HLA mismatch increases risk of immune-mediated graft rejection.", "protein": "human leukocyte antigen (HLA)", "relationship_type": "biomarker", "source_pmcid": "PMC12331733" }, { "confidence": "medium", "disease": "BK virus infection", "glycan_involvement": "Glycosylation modulates HLA stability and immune interactions.", "mechanism": "HLA type influences susceptibility to BK virus post-transplant.", "protein": "human leukocyte antigen (HLA)", "relationship_type": "biomarker", "source_pmcid": "PMC12331733" }, { "confidence": "medium", "disease": "BK virus infection", "glycan_involvement": "Glycosylation maintains antibody half-life, affecting immunosuppressive potency.", "mechanism": "Immunosuppression with basiliximab increases risk of BK virus reactivation.", "protein": "basiliximab (Simulect)", "relationship_type": "causal", "source_pmcid": "PMC12331733" }, { "confidence": "medium", "disease": "hypertension", "glycan_involvement": "Glycosylation influences pharmacokinetics and side effect profile.", "mechanism": "Erythropoietin therapy may increase blood pressure in renal patients.", "protein": "erythropoietin stimulating agent", "relationship_type": "causal", "source_pmcid": "PMC12331733" }, { "confidence": "high", "disease": "Spread through air spaces (STAS)", "glycan_involvement": "THBS1 is a glycoprotein; glycosylation modulates its adhesive and signaling functions.", "mechanism": "THBS1 mediates cell\u2013cell and cell\u2013matrix interactions, promotes EMT and TGF-\u03b2 pathway activation, facilitating tumor cell dissemination into air spaces.", "protein": "THBS1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "high", "disease": "Spread through air spaces (STAS)", "glycan_involvement": "N-glycosylation is essential for MHC II complex stability and antigen presentation.", "mechanism": "High HLA-DRB5 expression in tumor cells is associated with absence of STAS and better prognosis, likely via enhanced antigen presentation and adaptive immunity.", "protein": "HLA-DRB5", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Aberrant O-glycosylation of MUC1 alters cell adhesion and immune evasion.", "mechanism": "Upregulated in malignant epithelial cells, MUC1 promotes tumor initiation and progression.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation affects CEACAM6-mediated cell adhesion and signaling.", "mechanism": "CEACAM6 is upregulated in tumor cells, contributing to malignancy and invasion.", "protein": "CEACAM6", "protein_enriched": { "function": "Cell surface glycoprotein that plays a role in cell adhesion and tumor progression (PubMed:10910050, PubMed:11590190, PubMed:1378450, PubMed:16204051, PubMed:2022629, PubMed:2803308, PubMed:8776764). ", "gene_name": "CEACAM6", "glycan_count": 10, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX", "G53434XO", "G71784JC", "G92050GC", "G62765YT", "G28681TP", "G80920RR", "G57321FI" ], "uniprot_id": "P40199" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Spread through air spaces (STAS)", "glycan_involvement": "N-glycosylation regulates integrin function and cell migration.", "mechanism": "Elevated ITGA2 expression in air space tumor cells marks EMT activation and increased invasiveness.", "protein": "ITGA2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Spread through air spaces (STAS)", "glycan_involvement": "Glycosylation is required for CD73 cell surface localization and enzymatic activity.", "mechanism": "Upregulated in STAS compartments, NT5E promotes immunosuppression and tumor spread.", "protein": "NT5E (CD73)", "relationship_type": "biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation affects CD20 stability and immune signaling.", "mechanism": "High MS4A1 expression in immune compartments correlates with increased B-cell infiltration and better prognosis.", "protein": "MS4A1 (CD20)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation modulates tetraspanin interactions and signaling.", "mechanism": "CD37 expression on B cells promotes survival and apoptosis signaling, associated with improved outcomes.", "protein": "CD37", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Non-small-cell lung cancer (NSCLC)", "glycan_involvement": "BLK function is modulated by glycoprotein interactions in B-cell signaling.", "mechanism": "BLK regulates B-cell proliferation and differentiation; high expression inhibits tumor growth and glycolysis.", "protein": "BLK", "protein_enriched": { "function": "Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosin", "gene_name": "BLK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51451" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "medium", "disease": "Spread through air spaces (STAS)", "glycan_involvement": "CXCL14 is a glycoprotein; glycosylation may affect chemokine-receptor interactions.", "mechanism": "CXCL14 promotes EMT and tumor cell migration into air spaces via ACKR2 and TGF-\u03b2 signaling.", "protein": "CXCL14", "protein_enriched": { "function": "Potent chemoattractant for neutrophils, and weaker for dendritic cells. Not chemotactic for T-cells, B-cells, monocytes, natural killer cells or granulocytes. Does not inhibit proliferation of myeloid", "gene_name": "CXCL14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95715" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12331751" }, { "confidence": "high", "disease": "MYH9-related disease (MYH9-RD)", "glycan_involvement": "NMMHC-IIA is a glycoprotein; glycosylation may affect protein stability and cellular localization, but specific glycan changes not detailed.", "mechanism": "Mutations in MYH9 gene encoding NMMHC-IIA cause abnormal protein aggregation in leukocytes and platelets, leading to macrothrombocytopenia and May-Hegglin inclusions.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "medium", "disease": "Nephropathy (progressive kidney disease)", "glycan_involvement": "Glycosylation may modulate NMMHC-IIA function in podocytes, but not directly addressed.", "mechanism": "MYH9 mutations (e.g., p.E1841K) alter podocyte structure, increasing susceptibility to injury and renal dysfunction.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "medium", "disease": "Sensorineural deafness", "glycan_involvement": "No direct evidence in article; possible indirect effects via glycoprotein function.", "mechanism": "MYH9 mutations disrupt cytoskeletal function in auditory cells, leading to hearing loss.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "medium", "disease": "Presenile cataract", "glycan_involvement": "Not specified.", "mechanism": "MYH9 mutations affect lens cell cytoskeleton, predisposing to early cataract formation.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "medium", "disease": "Chronic liver enzyme abnormality", "glycan_involvement": "Not specified.", "mechanism": "MYH9 mutations associated with elevated AST/ALT in ~50% of MYH9-RD patients.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "high", "disease": "May-Hegglin anomaly (inclusion bodies)", "glycan_involvement": "Glycosylation may influence aggregation propensity, but not detailed.", "mechanism": "Mutant NMMHC-IIA aggregates in leukocytes, forming May-Hegglin inclusions, a diagnostic feature of MYH9-RD.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "biomarker", "source_pmcid": "PMC12331753" }, { "confidence": "high", "disease": "Macrothrombocytopenia", "glycan_involvement": "Platelet glycoprotein function may be affected; not directly discussed.", "mechanism": "MYH9 mutations disrupt platelet formation, resulting in large, reduced-number platelets.", "protein": "Non-muscle myosin heavy chain IIA (NMMHC-IIA)", "relationship_type": "causal", "source_pmcid": "PMC12331753" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "Aggrecan is heavily glycosylated; glycosaminoglycan chains are critical for disc hydration and function.", "mechanism": "Loss of aggrecan correlates with ECM degradation and disc degeneration.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "biomarker", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "Col2A1 is glycosylated; glycosylation affects fibril stability and ECM integrity.", "mechanism": "Decreased Col2A1 expression marks disc matrix breakdown.", "protein": "Type II Collagen (Col2A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "MMP-13 is glycosylated; glycosylation modulates secretion and activity.", "mechanism": "MMP-13 upregulation leads to collagen and aggrecan degradation in IDD.", "protein": "MMP-13", "protein_enriched": { "function": "Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III colla", "gene_name": "MMP13", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P45452" }, "relationship_type": "causal", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "ADAMTS-5 glycosylation affects substrate recognition and proteolytic activity.", "mechanism": "ADAMTS-5 mediates aggrecan cleavage, promoting ECM breakdown in IDD.", "protein": "ADAMTS-5", "protein_enriched": { "function": "Metalloproteinase that plays an important role in connective tissue organization, development, inflammation and cell migration. Extracellular matrix (ECM) degrading enzyme that show proteolytic activi", "gene_name": "ADAMTS5", "glycan_count": 5, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G43417UB", "G81006GJ", "G49108TO", "G61491DK" ], "uniprot_id": "Q9UNA0" }, "relationship_type": "causal", "source_pmcid": "PMC12331791" }, { "confidence": "medium", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "SIRT1 is glycosylated; glycosylation may regulate nuclear localization and activity.", "mechanism": "Activation of SIRT1 protects NPCs from apoptosis, senescence, and inflammation.", "protein": "SIRT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "NF-\u03baB p65 glycosylation can modulate transcriptional activity.", "mechanism": "NF-\u03baB activation drives inflammation and catabolic gene expression in IDD.", "protein": "NF-\u03baB p65 (RELA)", "relationship_type": "causal", "source_pmcid": "PMC12331791" }, { "confidence": "medium", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "Nrf2 glycosylation may affect stability and nuclear translocation.", "mechanism": "Nrf2 activation enhances antioxidant defenses and protects against oxidative stress-induced disc degeneration.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331791" }, { "confidence": "medium", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "Bcl-2 glycosylation influences mitochondrial localization and anti-apoptotic function.", "mechanism": "Upregulation of Bcl-2 inhibits apoptosis in disc cells.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "TLR4 N-glycosylation is essential for cell surface expression and ligand binding.", "mechanism": "TLR4 activation increases inflammatory cytokine release and ECM degradation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12331791" }, { "confidence": "medium", "disease": "Intervertebral Disc Degeneration (IDD)", "glycan_involvement": "Beclin-1 glycosylation may regulate autophagy induction.", "mechanism": "Beclin-1 promotes autophagy, protecting disc cells from degeneration.", "protein": "Beclin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12331791" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function in inflammation.", "mechanism": "CRP is elevated in the acute phase and predicts risk of chronic cardiac dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "high", "disease": "Chronic cardiac dysfunction", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "High acute-phase CRP (>127.79 mg/L) predicts later subclinical cardiac dysfunction in KD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Albumin glycosylation status may affect its anti-inflammatory properties.", "mechanism": "Low albumin in acute phase reflects inflammation and predicts IVIG resistance.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Platelet glycoprotein glycosylation regulates platelet activation and aggregation.", "mechanism": "Platelet count changes reflect inflammation and vascular injury in KD.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "Glycosylation influences CRP's interaction with immune cells.", "mechanism": "CRP elevation correlates with myocardial inflammation in KD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "medium", "disease": "Coronary artery aneurysm", "glycan_involvement": "Glycosylation may affect CRP's vascular targeting.", "mechanism": "CRP levels reflect severity of vascular inflammation and risk of aneurysm.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "low", "disease": "Chronic cardiac dysfunction", "glycan_involvement": "Altered glycosylation may reduce albumin's protective effects.", "mechanism": "Low albumin is associated with worse cardiac outcomes post-KD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332656" }, { "confidence": "low", "disease": "Coronary artery aneurysm", "glycan_involvement": "Glycosylation modulates platelet-endothelium interactions.", "mechanism": "Platelet activation contributes to thrombosis in aneurysms.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12332656" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect HDL structure and function", "mechanism": "Promotes cholesterol efflux from macrophages, anti-inflammatory and antioxidant effects", "protein": "Apolipoprotein A-I (ApoA-I)", "relationship_type": "protective", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Glycosylation may modulate CETP activity", "mechanism": "Genetic variants increasing CETP activity raise HDL-C but paradoxically increase CAD risk", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "causal", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation may affect receptor function", "mechanism": "Loss-of-function mutations increase HDL-C but also ASCVD risk due to impaired cholesterol delivery to liver", "protein": "SR-BI", "relationship_type": "causal", "source_pmcid": "PMC12332936" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may influence transporter stability", "mechanism": "Mediates cholesterol efflux to ApoA-I; mutations impair HDL formation and increase atherosclerosis risk", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects enzyme activity", "mechanism": "Antioxidant enzyme on HDL prevents LDL oxidation", "protein": "PON1", "relationship_type": "protective", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Infection (e.g., trypanosomiasis)", "glycan_involvement": "Glycosylation may affect immune recognition", "mechanism": "Directly neutralizes parasites as part of innate immunity", "protein": "ApoL1", "relationship_type": "protective", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for enzymatic activity", "mechanism": "Esterifies cholesterol on HDL, enabling maturation and reverse cholesterol transport", "protein": "LCAT", "protein_enriched": { "function": "Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to ch", "gene_name": "LCAT", "glycan_count": 28, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G12341GU", "G22310AV", "G27947YN", "G48414YA", "G66760KM", "G70232NH", "G81263BG", "G57321FI", "G04854VP", "G33791AF", "G63041LO", "G20425TQ", "G22388FD", "G23863VK", "G29857RC", "G36191CD", "G50045TK", "G63889NK", "G72797UR", "G74286KY", "G78059CC", "G86357DX", "G90093AU" ], "uniprot_id": "P04180" }, "relationship_type": "protective", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Hyperglycemia may alter glycosylation, affecting function", "mechanism": "Altered HDL proteome in diabetes impairs cholesterol efflux and anti-inflammatory function", "protein": "ApoA-I", "relationship_type": "biomarker", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation modulates function", "mechanism": "Enrichment of HDL with ApoC-III is associated with pro-inflammatory and pro-atherogenic properties", "protein": "ApoC-III", "relationship_type": "causal", "source_pmcid": "PMC12332936" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Altered glycosylation patterns in CKD", "mechanism": "Dysfunctional HDL (altered glycoprotein composition) associated with increased mortality risk", "protein": "HDL (multiple glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12332936" }, { "confidence": "high", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Recognizes mannose glycans; glycosylation critical for ligand binding.", "mechanism": "Promotes anti-inflammatory M2 macrophage polarization, aiding tissue repair.", "protein": "CD206 (Mannose receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332952" }, { "confidence": "high", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Glycosylation affects cell surface expression and immune signaling.", "mechanism": "Marker of pro-inflammatory M1 macrophages; elevated in chronic wounds.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332952" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates ligand recognition and signaling.", "mechanism": "Activation drives inflammatory cytokine production via MyD88/MAPK pathway.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12332952" }, { "confidence": "high", "disease": "Diabetic wound healing impairment", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Promotes angiogenesis and tissue regeneration; upregulated by GDNPs.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332952" }, { "confidence": "medium", "disease": "Vascular dysfunction", "glycan_involvement": "Glycosylation influences cell adhesion and migration.", "mechanism": "Endothelial marker; reduced expression indicates impaired angiogenesis.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12332952" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Adaptor for TLR4 signaling; drives MAPK pathway and cytokine release.", "protein": "MyD88", "protein_enriched": { "function": "Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575, PubMed:33718825, PubMed:37971847). Acts via IRAK", "gene_name": "MYD88", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99836" }, "relationship_type": "causal", "source_pmcid": "PMC12332952" }, { "confidence": "medium", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Glycosylation modulates immune cell interactions.", "mechanism": "M1 macrophage marker; elevated in non-healing wounds.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332952" }, { "confidence": "medium", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Glycosylation affects fibril formation and stability.", "mechanism": "Major ECM component; increased synthesis promotes wound closure.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12332952" }, { "confidence": "low", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Cell cycle regulator; reduced in oxidative stress, restored by GDNPs.", "protein": "Cyclin B1", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G2/M (mitosis) transition", "gene_name": "CCNB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14635" }, "relationship_type": "biomarker", "source_pmcid": "PMC12332952" }, { "confidence": "low", "disease": "Diabetic wound healing impairment", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Myofibroblast marker; increased expression correlates with wound contraction.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12332952" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation at N37/N134/N135 regulates HMGB1 nuclear export and extracellular release, impacting its pathogenic role.", "mechanism": "HMGB1 released from apoptotic osteocytes promotes osteoclastogenesis and bone resorption via RAGE/TLRs, leading to bone loss.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Osteoarthritis (OA)", "glycan_involvement": "N-glycosylation modulates HMGB1 secretion and inflammatory activity.", "mechanism": "HMGB1 is upregulated in synovial fluid, cartilage, and subchondral bone, promoting inflammation and bone resorption.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "N-glycosylation facilitates HMGB1 extracellular release and pro-inflammatory signaling.", "mechanism": "HMGB1 promotes osteoclast differentiation via RAGE/TLR4, enhancing bone resorption in periodontal lesions.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Bone injury/fracture", "glycan_involvement": "N-glycosylation and O-GlcNAcylation regulate HMGB1 release and chemotactic activity.", "mechanism": "Transient HMGB1 elevation recruits osteoblasts/BMSCs and promotes angiogenesis, accelerating bone healing.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12333100" }, { "confidence": "medium", "disease": "Ankylosing spondylitis", "glycan_involvement": "N-glycosylation influences HMGB1 nuclear export and extracellular function.", "mechanism": "Oxidized LDL induces HMGB1 release, which upregulates RANK and stimulates osteoclastogenesis.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Radiation-induced bone loss", "glycan_involvement": "N-glycosylation regulates HMGB1 release from dying cells.", "mechanism": "Radiation-induced osteocyte apoptosis releases HMGB1, promoting osteoclast differentiation and bone resorption.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "medium", "disease": "Glucocorticoid-induced osteoporosis", "glycan_involvement": "N-glycosylation affects HMGB1 secretion and activity.", "mechanism": "Glucocorticoid-induced osteocyte apoptosis increases HMGB1 release, enhancing osteoclastogenesis.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Sepsis/endotoxemia", "glycan_involvement": "N-glycosylation modulates HMGB1 secretion and inflammatory potency.", "mechanism": "Extracellular HMGB1 (especially B-box domain) induces cytokine storms and lethal inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12333100" }, { "confidence": "medium", "disease": "Tumor (bone context)", "glycan_involvement": "N-glycosylation and O-GlcNAcylation regulate HMGB1\u2019s extracellular functions.", "mechanism": "HMGB1 promotes angiogenesis and M2 macrophage polarization, supporting tumor growth and bone remodeling.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12333100" }, { "confidence": "medium", "disease": "Autoimmune diseases (general)", "glycan_involvement": "N-glycosylation and O-GlcNAcylation modulate HMGB1\u2019s immune signaling.", "mechanism": "HMGB1 drives M1 macrophage polarization and inflammatory cytokine release, contributing to disease progression.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12333100" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "TNF-alpha is glycosylated, affecting its stability and secretion.", "mechanism": "Elevated TNF-alpha indicates hepatic inflammation after doxorubicin exposure.", "protein": "TNF-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "Caspase-3 glycosylation may regulate its activation and localization.", "mechanism": "Increased caspase-3 expression marks apoptosis in liver tissue after doxorubicin.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "PON-1 glycosylation influences its stability and antioxidant function.", "mechanism": "Reduced PON-1 activity reflects oxidative stress and liver dysfunction post-doxorubicin.", "protein": "Paraoxonase-1 (PON-1)", "protein_enriched": { "function": "Involved in the response to variation in environmental oxygen levels by targeting the hypoxia-inducible transcription factor hif-1 for proteasomal degradation when oxygen levels are normal (around 20%", "gene_name": "vhl-1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q19213" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "medium", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "Glycosylation modulates ARES enzymatic activity.", "mechanism": "Decreased ARES activity is associated with increased oxidative damage in liver.", "protein": "Arylesterase (ARES)", "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "medium", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "CRP glycosylation affects its ligand binding and clearance.", "mechanism": "Elevated CRP indicates acute-phase inflammatory response in liver injury.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates TNF-alpha receptor interactions.", "mechanism": "TNF-alpha drives inflammatory signaling in hepatic tissue.", "protein": "TNF-alpha", "relationship_type": "causal", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Apoptosis", "glycan_involvement": "Glycosylation may affect caspase-3 activation.", "mechanism": "Caspase-3 executes apoptosis in hepatocytes after doxorubicin.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "causal", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation is essential for PON-1 stability and function.", "mechanism": "PON-1 acts as an antioxidant, mitigating oxidative stress in liver.", "protein": "Paraoxonase-1 (PON-1)", "protein_enriched": { "function": "Involved in the response to variation in environmental oxygen levels by targeting the hypoxia-inducible transcription factor hif-1 for proteasomal degradation when oxygen levels are normal (around 20%", "gene_name": "vhl-1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q19213" }, "relationship_type": "protective", "source_pmcid": "PMC12333101" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may influence TNF-alpha's neuroimmune effects.", "mechanism": "Elevated TNF-alpha is linked to depressive symptoms in cancer patients.", "protein": "TNF-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12333101" }, { "confidence": "medium", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "Potential modulation of caspase-3 activity by glycosylation.", "mechanism": "Agomelatine reduces caspase-3 expression, protecting against apoptosis.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333101" }, { "confidence": "high", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation modulates ICAM1 stability and cell adhesion.", "mechanism": "Upregulated in conditioned MSC; mediates immunomodulation and T cell interaction, contributing to disease amelioration.", "protein": "ICAM1 (CD54)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333171" }, { "confidence": "high", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation critical for enzymatic activity and surface expression.", "mechanism": "Upregulated in cMSC; inhibition reduces T cell proliferation, indicating a role in immunosuppression.", "protein": "CD26 (DPP4)", "protein_enriched": { "function": "Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:172872", "gene_name": "DPP4", "glycan_count": 92, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G10019LZ", "G12793SR", "G13131HA", "G22310AV", "G30740WO", "G41882MT", "G48414YA", "G57776ZS", "G57888GL", "G62461SM", "G82348BZ", "G22768VO", "G42227JK", "G56014GC", "G81315DD", "G81980VO", "G06356OH", "G56784JY", "G00395TQ", "G01650EU", "G02815KT", "G02886BB", "G10486CT", "G27058EU", "G28681TP", "G37399XV", "G46691LC", "G59626AS", "G72747WU", "G87661QW", "G92050GC", "G00912UN", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G15664MX", "G18647XP", "G20210JR", "G23294PN", "G23719VF", "G23984SE", "G27126ED", "G28541PG", "G28622IK", "G29184RN", "G29299MO", "G31852PQ", "G31986NC", "G37881RL", "G38663NM", "G39446WN", "G41071NU", "G41247ZX", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G47644PP", "G47748JZ", "G50282JC", "G59924QI", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G70441OD", "G70619PT", "G77547TA", "G80920RR", "G83646BJ", "G85269DF", "G86182NS", "G87123QX", "G90382BL", "G90659AW", "G92275SC", "G95865ZB", "G96091TT", "G40926MX", "G68490OW", "G74724QE", "G79666IR", "G84225JN", "G84452RH", "G49108TO" ], "uniprot_id": "P27487" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation affects ligand-receptor interaction with PD-1.", "mechanism": "Upregulated in cMSC; contributes to T cell inhibition and immune tolerance.", "protein": "PD-L2 (PDCD1LG2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Highly secreted by cMSC; modulates inflammation and immune response.", "protein": "IL6", "relationship_type": "biomarker", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Secreted by cMSC; acts as a decoy receptor for RANKL, modulating immune cell survival.", "protein": "TNFRSF11B (OPG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "Binds \u03b2-galactoside glycans on cell surfaces.", "mechanism": "Secreted by cMSC; binds glycan structures on immune cells, promoting immunosuppression.", "protein": "Galectin-1 (Gal-1)", "relationship_type": "protective", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "Binds poly-N-acetyllactosamine structures on glycoproteins.", "mechanism": "Secreted by cMSC; modulates immune cell activation and apoptosis.", "protein": "Galectin-3 (Gal-3)", "relationship_type": "protective", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "Contains glycosylation sites important for secretion.", "mechanism": "Secreted by cMSC; promotes clearance of apoptotic cells and immune tolerance.", "protein": "MFGE8 (Lactadherin)", "protein_enriched": { "function": "Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents", "gene_name": "Tff1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q08423" }, "relationship_type": "protective", "source_pmcid": "PMC12333171" }, { "confidence": "low", "disease": "Myasthenia Gravis", "glycan_involvement": "Heavily glycosylated, impacting ECM interactions.", "mechanism": "Secreted by cMSC; involved in extracellular matrix remodeling and immune regulation.", "protein": "SPON1 (Spondin-1)", "relationship_type": "protective", "source_pmcid": "PMC12333171" }, { "confidence": "medium", "disease": "Myasthenia Gravis", "glycan_involvement": "N-glycosylation essential for peptide loading and surface expression.", "mechanism": "Upregulated in \u03b3MSC; involved in antigen presentation and immune activation.", "protein": "HLA class I", "relationship_type": "biomarker", "source_pmcid": "PMC12333171" }, { "confidence": "high", "disease": "AKI", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and immune signaling.", "mechanism": "PD-1 blockade by inhibitors can trigger immune-mediated renal injury leading to AKI.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "AKI", "glycan_involvement": "PD-L1 glycosylation regulates its cell surface expression and immune interactions.", "mechanism": "PD-L1 inhibition disrupts immune tolerance, increasing risk of immune-mediated AKI.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates PD-1 receptor function and antibody binding.", "mechanism": "PD-1 inhibitors enhance antitumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation of PD-L1 is critical for its stability and immune checkpoint function.", "mechanism": "PD-L1 inhibitors block immune evasion by tumors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333227" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "Prealbumin is a glycoprotein; glycosylation may affect its serum half-life.", "mechanism": "Low prealbumin levels are associated with increased AKI risk in PD-1/PD-L1-treated patients.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "Glycosylation of PD-L1 influences immune recognition and toxicity profile.", "mechanism": "PD-L1 blockade can cause irAEs including renal toxicity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "Immune-related adverse events (irAEs)", "glycan_involvement": "Glycosylation status may modulate PD-1 signaling and adverse event risk.", "mechanism": "PD-1 inhibition can lead to loss of peripheral tolerance and irAEs.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12333227" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may influence prealbumin's stability and diagnostic utility.", "mechanism": "Prealbumin levels reflect nutritional status and may correlate with cancer prognosis.", "protein": "Prealbumin (Transthyretin)", "relationship_type": "biomarker", "source_pmcid": "PMC12333227" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "N-glycosylation affects PD-L1 detection and quantification.", "mechanism": "PD-L1 expression may predict risk of AKI during immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333227" }, { "confidence": "medium", "disease": "AKI", "glycan_involvement": "Glycosylation may impact PD-1's role as a biomarker.", "mechanism": "PD-1 expression may be associated with AKI risk in treated patients.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333227" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin; reflects chronic hyperglycemia.", "mechanism": "HbA1c is a component of eGDR, which is negatively associated with heart failure risk in diabetes/prediabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycation of hemoglobin correlates with blood glucose levels.", "mechanism": "HbA1c is used to diagnose and monitor diabetes; higher levels indicate poor glycemic control.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "high", "disease": "Prediabetes", "glycan_involvement": "Glycation reflects intermediate hyperglycemia.", "mechanism": "HbA1c is used to identify prediabetes; intermediate levels indicate increased risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Chronic glycation promotes microvascular damage.", "mechanism": "Elevated HbA1c is associated with increased risk of diabetic nephropathy.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "medium", "disease": "Diabetic peripheral neuropathy", "glycan_involvement": "Glycation contributes to nerve damage.", "mechanism": "High HbA1c levels are linked to increased risk of neuropathy.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "low", "disease": "Female infertility", "glycan_involvement": "Glycation may affect reproductive tissues.", "mechanism": "Elevated HbA1c is associated with increased risk of infertility in women with diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycation promotes vascular injury.", "mechanism": "High HbA1c is linked to increased risk of stroke in diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycation accelerates atherosclerosis.", "mechanism": "Elevated HbA1c is associated with increased risk of ischemic heart disease.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "low", "disease": "Thrombosis", "glycan_involvement": "Glycation alters coagulation pathways.", "mechanism": "Higher HbA1c levels are associated with increased risk of thrombosis in diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycation damages renal microvasculature.", "mechanism": "Elevated HbA1c is linked to increased risk of CKD in diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333258" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "PD-L1 glycosylation regulates its stability and immune evasion.", "mechanism": "CSN5-mediated degradation of PD-L1 enhances immune clearance of senescent tumor cells.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333312" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "O-GlcNAcylation downregulation is linked to senescence induction.", "mechanism": "OGT inhibition shifts therapy-induced senescence to apoptosis, improving response.", "protein": "OGT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "ICAM-1 glycosylation affects immune cell interactions.", "mechanism": "SASP-induced ICAM-1 expression promotes NK cell-mediated killing of senescent tumor cells.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "protective", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "MHC class II glycosylation modulates antigen presentation.", "mechanism": "Senescent melanocytes upregulate MHC class II, enhancing adaptive immune activation.", "protein": "MHC class II", "relationship_type": "protective", "source_pmcid": "PMC12333312" }, { "confidence": "high", "disease": "Esophageal cancer", "glycan_involvement": "CD59 is a GPI-anchored glycoprotein; glycosylation affects complement regulation.", "mechanism": "CD59 overexpression suppresses senescence via Src kinase, conferring radio-resistance.", "protein": "CD59", "protein_enriched": { "function": "Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation (PubMed:11882685, PubMed:1698710, PubMed:2475111, PubMed:24", "gene_name": "CD59", "glycan_count": 226, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G51287LK", "G60554YG", "G74724QE", "G31685JQ", "G12728EY", "G22625SJ", "G47448YK", "G49108TO", "G00176HZ", "G00273SJ", "G00912UN", "G02030ZB", "G02315DX", "G02528FI", "G02815KT", "G03382KH", "G04657PL", "G05962QB", "G06247RL", "G06290IR", "G06330RB", "G06356OH", "G07246CJ", "G07483YN", "G07755XJ", "G08520NM", "G08918WF", "G09831WQ", "G10846ZT", "G11629QQ", "G12341GU", "G12793SR", "G13131HA", "G13191RB", "G13728QT", "G13749ZZ", "G14456RI", "G14882EB", "G14972EH", "G14994KB", "G15169WU", "G15488CF", "G16768LX", "G16828VN", "G17208MA", "G18647XP", "G20312EM", "G22310AV", "G22768VO", "G23133OF", "G23863VK", "G23984SE", "G24835MQ", "G24954UD", "G25418HZ", "G27058EU", "G27126ED", "G27919IH", "G29501UT", "G30740WO", "G30751OD", "G30799SW", "G31596VW", "G31615DN", "G31852PQ", "G32788FZ", "G34617SM", "G34989PA", "G36013ES", "G36134VO", "G36191CD", "G36379GD", "G37412TK", "G37773JL", "G37818NZ", "G39064KU", "G39213VZ", "G39595FH", "G40124HY", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41405QQ", "G42124LM", "G43223CG", "G43669FQ", "G44173IH", "G44215PV", "G44413JJ", "G44778BV", "G45395BF", "G45883VE", "G46487SG", "G46665ZP", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G48414YA", "G50120TH", "G50427EO", "G50856PC", "G51413EV", "G52114WE", "G52358QA", "G52589SM", "G55220VL", "G56087PR", "G56518TU", "G57557NS", "G57776ZS", "G57888GL", "G57939IT", "G58596DI", "G58598BO", "G58667NI", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G61207RZ", "G61256FT", "G61505ZR", "G61806WR", "G62765YT", "G63628AV", "G63640QH", "G63889NK", "G64227LK", "G64394MX", "G64527OM", "G65019XG", "G65092SV", "G66621EA", "G66760KM", "G67164EE", "G67900CJ", "G68833MP", "G69521XL", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71146HJ", "G71463BG", "G71919QK", "G72667IM", "G72797UR", "G72886NH", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77023TY", "G77149EE", "G77669RF", "G78059CC", "G78502KD", "G78649WQ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80858MF", "G80920RR", "G80966KZ", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82348BZ", "G82443XX", "G82830MN", "G83229XP", "G83633GK", "G83646BJ", "G84452RH", "G85269DF", "G85282JO", "G85737WG", "G86182NS", "G86226EA", "G86234IN", "G86357DX", "G86408JD", "G86795LJ", "G86880BF", "G87123QX", "G87618BG", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G90717TP", "G91473PK", "G91636VS", "G92062TF", "G92081HT", "G92135MA", "G92275SC", "G93141AZ", "G93993PD", "G94470IW", "G94831VI", "G95177YH", "G95865ZB", "G95977AE", "G98611JV", "G57321FI", "G01079KY", "G16389EC", "G31544HA", "G46687AB", "G50045TK", "G51519NL", "G71269BI", "G75727PF", "G80218BM", "G83461WR", "G90093AU" ], "uniprot_id": "P13987" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "FGGY is glycosylated; modification may affect metabolic function.", "mechanism": "FGGY knockdown activates p53-dependent senescence-associated heterochromatin foci.", "protein": "FGGY", "relationship_type": "causal", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CBX4 is a glycoprotein; SUMOylation and glycosylation may interact.", "mechanism": "CBX4 SUMOylates YAP1, inhibiting Hippo pathway and senescence induction, promoting chemoresistance.", "protein": "CBX4", "protein_enriched": { "function": "Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, Pu", "gene_name": "USP7", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G62765YT" ], "uniprot_id": "Q93009" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "YAP1 is glycosylated; modification may affect nuclear localization.", "mechanism": "YAP1 stabilization by CBX4 SUMOylation inhibits senescence, driving tumor progression.", "protein": "YAP1", "relationship_type": "causal", "source_pmcid": "PMC12333312" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "IL6 glycosylation affects secretion and receptor binding.", "mechanism": "Senescent CAFs secrete IL6, promoting immunosuppression and tumor progression.", "protein": "IL6", "relationship_type": "causal", "source_pmcid": "PMC12333312" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CXCL12 glycosylation modulates chemokine activity.", "mechanism": "Senescence-associated CXCL12 secretion by CAFs drives immune evasion.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "causal", "source_pmcid": "PMC12333312" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No N-glycosylation detected; function independent of glycosylation.", "mechanism": "Promotes degradation of p53 tumor suppressor via E6AP binding, inhibiting apoptosis and facilitating malignant transformation.", "protein": "HPV-31 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No N-glycosylation detected; function independent of glycosylation.", "mechanism": "Disrupts Rb pathway, releasing E2F transcription factors and deregulating cell cycle progression.", "protein": "HPV-31 E7", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No N-glycosylation detected; function independent of glycosylation.", "mechanism": "Promotes p53 degradation and inhibits apoptosis, similar to HPV-31 E6.", "protein": "HPV-52 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No N-glycosylation detected; function independent of glycosylation.", "mechanism": "Disrupts Rb pathway, promoting cell cycle progression and oncogenesis.", "protein": "HPV-52 E7", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "HPV infection", "glycan_involvement": "No glycosylation; protein sequence used for detection.", "mechanism": "Presence and sequence of E6 used for subtype identification and risk stratification.", "protein": "HPV-31 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "HPV infection", "glycan_involvement": "No glycosylation; protein sequence used for detection.", "mechanism": "E6 sequence used for molecular epidemiology and subtype-specific diagnostics.", "protein": "HPV-52 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12333388" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "No glycosylation; epitope exposure due to random coil regions.", "mechanism": "Contains dominant B- and T-cell epitopes (e.g., 45\u201353, 55\u201361) suitable for vaccine design.", "protein": "HPV-31 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333388" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "No glycosylation; epitope exposure due to random coil regions.", "mechanism": "Dominant epitopes (e.g., 45\u201353, 110\u2013119) identified for vaccine development.", "protein": "HPV-52 E6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333388" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "No glycosylation; antigenicity linked to coil-rich regions.", "mechanism": "Contains immunodominant epitopes (e.g., 7\u201315, 29\u201341) for T-cell and B-cell response induction.", "protein": "HPV-31 E7", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333388" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "No glycosylation; antigenicity linked to coil-rich regions.", "mechanism": "Immunogenic epitopes (e.g., 23\u201327, 36\u201348, 53\u201359) identified for vaccine strategies.", "protein": "HPV-52 E7", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333388" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "ICAM-1 function and cell interactions depend on N-glycosylation.", "mechanism": "NF-\u03baB activation upregulates ICAM-1, promoting tumor cell adhesion, invasion, and metastasis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "VCAM-1 is N-glycosylated, affecting ligand binding and cell migration.", "mechanism": "NF-\u03baB induces VCAM-1 expression, facilitating tumor cell adhesion and metastasis.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "E-selectin binds sialylated glycans on tumor cells; its own glycosylation modulates function.", "mechanism": "NF-\u03baB upregulates ELAM-1, enhancing tumor-endothelial interactions and metastasis.", "protein": "ELAM-1 (E-selectin)", "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Chemoresistance in Osteosarcoma", "glycan_involvement": "MDR1 is N-glycosylated, which is essential for its stability and drug transport activity.", "mechanism": "NF-\u03baB activation increases MDR1 expression, leading to drug efflux and chemoresistance.", "protein": "MDR1 (P-glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Tumor Angiogenesis", "glycan_involvement": "VEGF is glycosylated, affecting secretion and receptor binding.", "mechanism": "NF-\u03baB upregulates VEGF, promoting angiogenesis in osteosarcoma.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Tumor Metastasis", "glycan_involvement": "MMP-9 is N-glycosylated, influencing secretion and activity.", "mechanism": "NF-\u03baB induces MMP-9, facilitating extracellular matrix degradation and metastasis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "medium", "disease": "Tumor Metastasis", "glycan_involvement": "MMP-2 is N-glycosylated, affecting enzyme stability.", "mechanism": "NF-\u03baB upregulates MMP-2, promoting invasion and metastasis.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Immune Escape in Osteosarcoma", "glycan_involvement": "PD-L1 N-glycosylation is critical for stability and immune checkpoint function.", "mechanism": "NF-\u03baB signaling increases PD-L1 expression, enabling immune evasion.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333507" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "Bcl-2 is reported to be glycosylated, which may affect its anti-apoptotic function.", "mechanism": "NF-\u03baB upregulates Bcl-2, inhibiting apoptosis and promoting tumor survival.", "protein": "Bcl-2", "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "EGF glycosylation modulates receptor binding and signaling.", "mechanism": "EGF induces NF-\u03baB activation, which promotes EMT, invasion, and metastasis.", "protein": "EGF", "relationship_type": "causal", "source_pmcid": "PMC12333507" }, { "confidence": "high", "disease": "Multidrug resistance", "glycan_involvement": "N-glycosylation critical for P-glycoprotein function and drug efflux.", "mechanism": "Resveratrol suppresses P-glycoprotein, reducing chemoresistance in GBM cells.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Potential O-glycosylation modulates p53 stability and activity.", "mechanism": "Resveratrol and temozolomide upregulate p53, promoting apoptosis and cell cycle arrest.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Cell cycle dysregulation in GBM", "glycan_involvement": "Glycosylation may affect p21 localization and degradation.", "mechanism": "Resveratrol downregulates p21, shifting cells toward apoptosis rather than cell cycle arrest.", "protein": "p21 (CDKN1A)", "relationship_type": "biomarker", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Cell cycle dysregulation in GBM", "glycan_involvement": "Glycosylation may regulate p27 stability.", "mechanism": "Resveratrol upregulates p27, inducing cell cycle arrest and apoptosis.", "protein": "p27 (CDKN1B)", "protein_enriched": { "function": "Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arres", "gene_name": "CDKN1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P46527" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Apoptosis resistance in GBM", "glycan_involvement": "N-glycosylation influences Bcl-2 anti-apoptotic function.", "mechanism": "Resveratrol and temozolomide decrease Bcl-2, sensitizing GBM cells to apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may affect Bax mitochondrial targeting.", "mechanism": "Resveratrol and temozolomide increase Bax, promoting apoptosis in GBM cells.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "N-glycosylation required for TRPM2 channel function.", "mechanism": "Resveratrol/5-fluorouracil downregulate TRPM2, reducing GBM cell viability.", "protein": "TRPM2", "protein_enriched": { "function": "Orphan receptor. May play a role in brain function", "gene_name": "GPR63", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9BZJ6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "O-glycosylation modulates \u03b2-catenin signaling.", "mechanism": "Resveratrol/5-fluorouracil downregulate \u03b2-catenin, inhibiting proliferation.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Cancer stem cell-driven GBM", "glycan_involvement": "O-glycosylation regulates Notch1 ligand binding and activation.", "mechanism": "Resveratrol combined with Notch inhibitors enhances autophagic/apoptotic cell death.", "protein": "Notch1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may affect AKT1 localization and activity.", "mechanism": "Resveratrol targets AKT1, suppressing tumor growth and invasiveness.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333572" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Carbohydrate-binding (galectin family); glycan recognition mediates immune modulation.", "mechanism": "Present in eosinophil granules in RA synovium; binds carbohydrates, may modulate inflammation.", "protein": "Charcot-Leyden crystal protein (Galectin-10)", "protein_enriched": { "function": "Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within c", "gene_name": "DYNC2I1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8WVS4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333626" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Elevated in RA synovium and blood; correlates with disease activity and eosinophil infiltration.", "protein": "Eosinophil peroxidase (EPX)", "protein_enriched": { "function": "Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living", "gene_name": "CAST", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20811" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12333626" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates cytotoxicity and immune interactions.", "mechanism": "Serum ECP levels increased in RA, especially with high severity and short duration.", "protein": "Eosinophil cationic protein (ECP)", "protein_enriched": { "function": "Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarizatio", "gene_name": "RNASE3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P12724" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333626" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Heavily glycosylated; glycosylation regulates cell adhesion and immune signaling.", "mechanism": "Secreted by regulatory eosinophils in synovium; promotes tissue healing and inflammation resolution.", "protein": "Osteopontin", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12333626" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation influences secretion and inhibitory activity.", "mechanism": "Released by regulatory eosinophils; may aid joint healing but high levels linked to thrombophilia.", "protein": "Serpin E1 (PAI-1)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12333626" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Produced by synovial cells and regulatory eosinophils; mediates ECM degradation and tissue remodeling.", "protein": "Matrix metallopeptidase 3 (MMP-3)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12333626" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates cell adhesion and leukocyte transmigration.", "mechanism": "Upregulated in RA; mediates eosinophil homing to inflamed joints via CD11b interaction.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12333626" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation regulates ligand binding and immune cell interactions.", "mechanism": "Promotes leukocyte adhesion and migration in RA synovium.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12333626" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation essential for immunomodulatory activity.", "mechanism": "Helminth-derived glycoprotein; anti-inflammatory and anti-osteoclastogenic effects in arthritis models.", "protein": "ES-62", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12333626" }, { "confidence": "low", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects protein stability and immune recognition.", "mechanism": "Contained in eosinophil granules; may contribute to tissue damage and inflammation.", "protein": "Major basic protein (MBP)", "protein_enriched": { "function": "", "gene_name": "ALDOC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09972" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333626" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-glycosylation of mucin-type proteins modulates tumor behavior.", "mechanism": "GALNT14 SNPs (especially rs9679162 and linked panel) predict recurrence and metastasis after surgery.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333627" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-glycosylation may regulate cytokine/chemokine secretion and TGF-\u03b2 signaling.", "mechanism": "High GALNT14 expression promotes M2-macrophage infiltration, supporting tumor progression.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "O-glycosylation affects cell death pathways and immune evasion.", "mechanism": "GALNT14 modulates immune microenvironment and ferroptosis sensitivity.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333627" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "O-glycosylation alters immune response to chemotherapy/immunotherapy.", "mechanism": "High GALNT14 expression linked to poor prognosis and immunogenic cell death modulation.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333627" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation of key proteins affects proliferation and therapy response.", "mechanism": "GALNT14 activity promotes tumorigenesis and drug resistance.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "O-glycosylation modulates signaling and cell death.", "mechanism": "GALNT14 regulates EGFR glycosylation, impacting mTOR pathway and ferroptosis.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "O-glycosylation affects cell death pathways.", "mechanism": "GALNT14 regulates ferroptosis sensitivity.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "low", "disease": "Polycystic ovary syndrome", "glycan_involvement": "O-glycosylation modulates cell fate.", "mechanism": "GALNT14 implicated in ferroptosis regulation.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "low", "disease": "Bronchopulmonary dysplasia", "glycan_involvement": "O-glycosylation affects cell survival.", "mechanism": "GALNT14 regulates ferroptosis in lung tissue.", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "causal", "source_pmcid": "PMC12333627" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "O-glycosylation modulates immune cell recruitment.", "mechanism": "GALNT14 is a hub gene for immune cell infiltration (dendritic cells, CD8+ T cells).", "protein": "GALNT14", "protein_enriched": { "function": "May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4", "gene_name": "RLN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333627" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "EGFRvIII is a glycosylated receptor; glycosylation affects ligand binding and immune recognition.", "mechanism": "EGFRvIII mutation drives tumor growth; targeted by engineered oncolytic HSV for selective virotherapy.", "protein": "EGFRvIII", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "high", "disease": "Malignant glioma", "glycan_involvement": "PD-1 glycosylation modulates receptor stability and immune signaling.", "mechanism": "PD-1 blockade enhances T cell-mediated antitumor immunity; used in combination with OVs.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "high", "disease": "Malignant glioma", "glycan_involvement": "PD-L1 glycosylation affects immune evasion and antibody binding.", "mechanism": "PD-L1 upregulation suppresses T cell activity; OVs induce PD-L1, necessitating checkpoint inhibition.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Malignant glioma", "glycan_involvement": "Nestin is glycosylated; glycosylation may affect filament assembly and tumor cell migration.", "mechanism": "Nestin promoter used for tumor-specific expression in engineered HSV (CAN-3110).", "protein": "Nestin", "protein_enriched": { "function": "Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF pro", "gene_name": "NES", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "CXCL11 glycosylation influences chemokine gradient and receptor binding.", "mechanism": "CXCL11 attracts CAR-T cells to tumor; expressed by oAd to enhance immunotherapy.", "protein": "CXCL11", "protein_enriched": { "function": "Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes. Induces calcium release in activated T-cells. Binds to CXCR3. May play an important role in CNS di", "gene_name": "CXCL11", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14625" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Malignant glioma", "glycan_involvement": "MMP-2 glycosylation regulates enzyme activity and substrate specificity.", "mechanism": "MMP-2 overexpression enables tumor-specific release of nanocarrier-encapsulated OVs.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Malignant glioma", "glycan_involvement": "Survivin glycosylation may affect protein stability and anti-apoptotic function.", "mechanism": "Survivin promoter drives selective replication of oncolytic Ad in tumor cells.", "protein": "Survivin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "high", "disease": "Malignant glioma", "glycan_involvement": "IL-12 glycosylation is essential for secretion and bioactivity.", "mechanism": "IL-12 expression by OVs enhances antitumor immunity and suppresses angiogenesis.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Malignant glioma", "glycan_involvement": "CD4 glycosylation modulates T cell receptor interactions.", "mechanism": "CD4+ T cell infiltration correlates with OV-induced antitumor immune response.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333633" }, { "confidence": "medium", "disease": "Malignant glioma", "glycan_involvement": "CD8 glycosylation affects T cell activation and antigen recognition.", "mechanism": "CD8+ T cell infiltration is a marker of effective OV-induced cytotoxic immunity.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333633" }, { "confidence": "high", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "Glycosylation affects immunoglobulin function and inflammatory response.", "mechanism": "Elevated globulin reflects systemic inflammation and predicts SKD severity.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "GGT is a glycosylated membrane enzyme; glycosylation modulates activity.", "mechanism": "Elevated GGT correlates with acute phase and liver involvement in SKD.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "high", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion and immune signaling.", "mechanism": "Lower platelet counts in SKD are associated with increased risk of coronary artery lesions and inflammation.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "CD19 is a glycosylated surface protein; glycosylation affects B-cell signaling.", "mechanism": "Elevated B-lymphocyte counts are linked to acute inflammation and SKD progression.", "protein": "CD3-CD19+ (B-lymphocyte marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "Albumin glycosylation status can affect vascular permeability.", "mechanism": "Lower albumin levels indicate severe inflammation and vascular leakage in SKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "Includes multiple glycoproteins; glycosylation influences immune response.", "mechanism": "Decreased total protein reflects systemic inflammation and poor prognosis in SKD.", "protein": "Total Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "high", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "CRP is glycosylated; glycan moieties modulate immune recognition.", "mechanism": "Elevated CRP is a marker of acute systemic inflammation in SKD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "RBP is glycosylated; glycosylation affects stability and clearance.", "mechanism": "Lower RBP levels are associated with severe inflammation and organ dysfunction in SKD.", "protein": "Retinol-binding protein (RBP)", "protein_enriched": { "function": "Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans ret", "gene_name": "RBP4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02753" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation modulates clotting function.", "mechanism": "Altered fibrinogen levels indicate coagulation abnormalities and inflammation in SKD.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "medium", "disease": "Severe Kawasaki Disease (SKD)", "glycan_involvement": "D-dimer fragments retain glycan structures from fibrinogen.", "mechanism": "Elevated D-dimer reflects increased fibrinolysis and vascular injury in SKD.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12333634" }, { "confidence": "high", "disease": "spondylodiscitis", "glycan_involvement": "CRP is a glycoprotein; its glycosylation is essential for stability and function as an inflammatory biomarker.", "mechanism": "CRP is elevated in response to inflammation caused by infection of the intervertebral discs and adjacent vertebrae.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333644" }, { "confidence": "high", "disease": "spinal infection", "glycan_involvement": "Glycosylation of CRP is required for its secretion and function.", "mechanism": "CRP levels rise in systemic inflammatory response to spinal infections, including those caused by C. striatum.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333644" }, { "confidence": "high", "disease": "discitis", "glycan_involvement": "Glycosylation affects CRP's serum half-life and detection.", "mechanism": "CRP is used clinically to monitor inflammation and response to therapy in discitis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333644" }, { "confidence": "high", "disease": "Multidrug-resistant UTI", "glycan_involvement": "Glycosylation affects ESBL enzyme stability and secretion.", "mechanism": "ESBL enzymes hydrolyze \u03b2-lactam antibiotics, causing resistance.", "protein": "Extended-spectrum \u03b2-lactamase (ESBL)", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Carbapenem-resistant Enterobacterales infection", "glycan_involvement": "Glycosylation modulates enzyme activity and localization.", "mechanism": "KPC enzymes hydrolyze carbapenems, conferring resistance.", "protein": "Carbapenemase (KPC)", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "medium", "disease": "Multidrug-resistant UTI", "glycan_involvement": "Glycosylation changes OMP conformation and function.", "mechanism": "Altered OMPs reduce antibiotic permeability.", "protein": "Outer membrane proteins (OMPs)", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "medium", "disease": "Multidrug-resistant UTI", "glycan_involvement": "Glycosylation influences pump assembly and activity.", "mechanism": "Efflux pumps expel antibiotics from bacterial cells.", "protein": "Efflux pump proteins", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Extensively drug-resistant UTI", "glycan_involvement": "Glycosylation may affect enzyme secretion and resistance level.", "mechanism": "ESBL production is a key driver of XDR phenotype.", "protein": "Extended-spectrum \u03b2-lactamase (ESBL)", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Extensively drug-resistant UTI", "glycan_involvement": "Glycosylation impacts enzyme stability and resistance spectrum.", "mechanism": "KPC co-expression with ESBL leads to XDR.", "protein": "Carbapenemase (KPC)", "relationship_type": "causal", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Glycosylation may affect detection and activity.", "mechanism": "ESBL presence indicates MDR UTI.", "protein": "Extended-spectrum \u03b2-lactamase (ESBL)", "relationship_type": "biomarker", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Glycosylation may influence diagnostic sensitivity.", "mechanism": "KPC presence signals carbapenem resistance.", "protein": "Carbapenemase (KPC)", "relationship_type": "biomarker", "source_pmcid": "PMC12333652" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Targeting glycosylation could modulate OMP function.", "mechanism": "OMPs are potential targets to restore antibiotic entry.", "protein": "Outer membrane proteins (OMPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333652" }, { "confidence": "medium", "disease": "Urinary tract infection (UTI)", "glycan_involvement": "Glycosylation may be targeted to disrupt pump function.", "mechanism": "Efflux pumps can be inhibited to restore antibiotic efficacy.", "protein": "Efflux pump proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12333652" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody recognition.", "mechanism": "Autoantibody against SS-A is diagnostic for pSS and reflects B-cell hyperactivity.", "protein": "SS-A (Ro60)", "relationship_type": "biomarker", "source_pmcid": "PMC12333870" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Autoantibody against Ro52 is commonly detected in pSS and correlates with disease activity.", "protein": "Ro52 (TRIM21)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2 (PubMed:16297862, PubMed:16316627, PubMed:16472766, PubMed:16880511, PubMed:18022694, PubMed:18", "gene_name": "TRIM21", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19474" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333870" }, { "confidence": "medium", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "Glycosylation may influence autoantigen presentation.", "mechanism": "Presence of anti-Jo-1 antibodies indicates autoimmune activation in pSS.", "protein": "Jo-1 (Histidyl-tRNA synthetase)", "protein_enriched": { "function": "Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance", "gene_name": "HARS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333870" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "Glycosylation of nuclear antigens affects autoantibody binding.", "mechanism": "Antinuclear antibodies are indicative of systemic autoimmunity in pSS.", "protein": "ANA", "relationship_type": "biomarker", "source_pmcid": "PMC12333870" }, { "confidence": "medium", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation regulates CD20 surface expression and immune cell interactions.", "mechanism": "B-cell infiltration (CD20+) in spleen contributes to splenomegaly in pSS.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC12333870" }, { "confidence": "medium", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation modulates CD23 function and immune activation.", "mechanism": "Activated B-cells (CD23+) are present in splenic tissue in pSS-associated splenomegaly.", "protein": "CD23", "relationship_type": "causal", "source_pmcid": "PMC12333870" }, { "confidence": "medium", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation affects T-cell receptor signaling.", "mechanism": "T-cell infiltration (CD3+) in spleen contributes to immune-mediated splenomegaly.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "causal", "source_pmcid": "PMC12333870" }, { "confidence": "medium", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation influences BCR signaling and cell survival.", "mechanism": "B-cell receptor component (CD79a+) marks B-cell expansion in spleen.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "causal", "source_pmcid": "PMC12333870" }, { "confidence": "low", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation may affect nuclear localization and function.", "mechanism": "Ki-67 positivity indicates proliferative activity in splenic lymphocytes.", "protein": "Ki-67", "relationship_type": "biomarker", "source_pmcid": "PMC12333870" }, { "confidence": "low", "disease": "Splenomegaly", "glycan_involvement": "Glycosylation modulates cell-cell interactions.", "mechanism": "CD5+ T/B cells contribute to immune dysregulation in splenic tissue.", "protein": "CD5", "relationship_type": "causal", "source_pmcid": "PMC12333870" }, { "confidence": "high", "disease": "Preterm birth in early-onset preeclampsia", "glycan_involvement": "CRP glycosylation modulates its stability and immune function.", "mechanism": "CRP reflects systemic inflammation and is independently associated with increased risk of preterm birth in EOPE.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "high", "disease": "Preterm birth in early-onset preeclampsia", "glycan_involvement": "N-glycosylation affects Cys-C secretion and clearance.", "mechanism": "Elevated Cys-C indicates renal endothelial damage, a key feature of EOPE and strong predictor of preterm birth.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "high", "disease": "Renal dysfunction in preeclampsia", "glycan_involvement": "Albumin glycosylation influences renal filtration and vascular leakage.", "mechanism": "Microalbuminuria reflects glomerular endothelial injury in EOPE.", "protein": "Microalbumin (albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Placental insufficiency", "glycan_involvement": "N-glycosylation is essential for ALP activity and placental localization.", "mechanism": "Elevated ALP may indicate placental ischemia or hepatic involvement in EOPE.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation regulates GGT membrane expression.", "mechanism": "Elevated GGT is associated with oxidative stress and inflammation in EOPE.", "protein": "Gamma-glutamyl transferase", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Placental abruption", "glycan_involvement": "Glycosylation affects AST stability.", "mechanism": "Elevated AST may reflect hepatic or placental injury in EOPE.", "protein": "Aspartate aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Placental abruption", "glycan_involvement": "Glycosylation modulates ALT secretion.", "mechanism": "Elevated ALT may indicate hepatic involvement in EOPE.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Capillary leakage", "glycan_involvement": "Albumin glycosylation affects vascular permeability.", "mechanism": "Low albumin levels indicate capillary leakage and vascular dysfunction in EOPE.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "medium", "disease": "Vascular endothelial injury", "glycan_involvement": "N-glycosylation is critical for fibrinogen function.", "mechanism": "Elevated FDPs reflect coagulation activation and endothelial injury in EOPE.", "protein": "Fibrinogen degradation products", "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "low", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation influences ferritin secretion.", "mechanism": "Altered ferritin levels are associated with inflammation and oxidative stress in EOPE.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12333876" }, { "confidence": "high", "disease": "Low-grade Inflammation", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP in serum indicates systemic inflammation in lactating mothers.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "N-glycosylation modulates albumin half-life and function.", "mechanism": "Serum albumin levels reflect nutritional and metabolic status.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Liver Stress", "glycan_involvement": "Glycosylation affects enzyme activity and secretion.", "mechanism": "Elevated alkaline phosphatase may indicate mild hepatic stress.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Antibiotic Resistance", "glycan_involvement": "Glycosylation regulates BCRP trafficking and substrate specificity.", "mechanism": "BCRP effluxes antibiotics into breast milk, facilitating resistance development.", "protein": "BCRP (ABCG2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Antibiotic Resistance", "glycan_involvement": "N-glycosylation modulates transporter localization and function.", "mechanism": "MRP2 transports xenobiotics/antibiotics into milk, impacting resistance.", "protein": "MRP2 (ABCC2)", "relationship_type": "causal", "source_pmcid": "PMC12334071" }, { "confidence": "high", "disease": "Infant Infection", "glycan_involvement": "O-glycosylation of IgA enhances mucosal immunity.", "mechanism": "Secretory IgA in milk protects infants from infections.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Mastitis", "glycan_involvement": "Glycosylation modulates antimicrobial activity.", "mechanism": "Lactoferrin in milk inhibits bacterial growth, reducing mastitis risk.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects iron-binding and receptor interaction.", "mechanism": "Transferrin levels reflect iron status and anemia risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Mastitis", "glycan_involvement": "Bacterial glycosylation may alter host-pathogen interactions.", "mechanism": "Protein A facilitates bacterial immune evasion in mastitis.", "protein": "Staphylococcus aureus Protein A", "relationship_type": "causal", "source_pmcid": "PMC12334071" }, { "confidence": "medium", "disease": "Antibiotic Resistance", "glycan_involvement": "Altered glycosylation may affect immune recognition and antibiotic binding.", "mechanism": "MRSA surface glycoproteins contribute to resistance transmission via milk.", "protein": "Methicillin-resistant Staphylococcus aureus (MRSA) surface proteins", "relationship_type": "causal", "source_pmcid": "PMC12334071" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Indirect; P-glycoprotein is a glycoprotein regulated by SMYD2.", "mechanism": "Overexpression promotes RCC development, metastasis, and drug resistance via miR-125b/DKK3 axis and upregulation of P-glycoprotein.", "protein": "SMYD2", "protein_enriched": { "function": "Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity req", "gene_name": "SMYD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG4" }, "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Autosomal dominant polycystic kidney disease (ADPKD)", "glycan_involvement": "Not directly specified.", "mechanism": "Upregulation drives cyst growth via methylation of STAT3 and NF-\u03baB p65, activating pro-inflammatory and proliferative feedback loops.", "protein": "SMYD2", "protein_enriched": { "function": "Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity req", "gene_name": "SMYD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Not specified.", "mechanism": "Promotes tubular apoptosis and inflammation via p53, caspase-3, and JNK-STAT3 pathways; inhibition is protective.", "protein": "SMYD2", "protein_enriched": { "function": "Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity req", "gene_name": "SMYD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Not specified.", "mechanism": "Drives fibrosis by methylating PTEN and activating TGF-\u03b2/Smad3, AKT/mTOR, and NF-\u03baB pathways; inhibition reduces fibrosis.", "protein": "SMYD2", "protein_enriched": { "function": "Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity req", "gene_name": "SMYD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Not specified.", "mechanism": "Activates renal fibroblasts and inflammation via NF-\u03baB p65 methylation under hyperglycemia; inhibition is anti-fibrotic.", "protein": "SMYD2", "protein_enriched": { "function": "Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity req", "gene_name": "SMYD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRG4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "EGFR is a glycoprotein upregulated by SMYD3.", "mechanism": "Overexpression promotes RCC progression via H3K4 methylation at oncogene promoters (e.g., NUF2, EGFR).", "protein": "SMYD3", "protein_enriched": { "function": "Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histo", "gene_name": "SMYD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7B4" }, "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Autosomal dominant polycystic kidney disease (ADPKD)", "glycan_involvement": "Not specified.", "mechanism": "Upregulation enhances cyst growth via H3K4me3 at proliferation/apoptosis genes and methylation of \u03b1-tubulin K40, promoting genomic instability.", "protein": "SMYD3", "protein_enriched": { "function": "Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histo", "gene_name": "SMYD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7B4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "EGFR is a glycoprotein whose expression is regulated by SMYD3.", "mechanism": "Promotes tubular regeneration and survival via H3K4me3-mediated EGFR/AKT activation; inhibition worsens injury.", "protein": "SMYD3", "protein_enriched": { "function": "Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histo", "gene_name": "SMYD3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7B4" }, "relationship_type": "protective", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "P-gP is a well-known glycoprotein; glycosylation is essential for its function.", "mechanism": "Upregulated by SMYD2, mediates chemoresistance in RCC.", "protein": "P-glycoprotein (P-gP)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "EGFR is a glycoprotein; glycosylation modulates its signaling.", "mechanism": "Upregulated by SMYD3 via H3K4 methylation, promoting tumor progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12334150" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "CD44 function and cell adhesion depend on glycosylation status.", "mechanism": "Downregulated in pancreatitis; involved in apoptosis and immune cell infiltration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "CD4 is heavily glycosylated, affecting T cell activation and immune response.", "mechanism": "Downregulated in pancreatitis; associated with central memory CD4 T cell infiltration.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Glycosylation disorders", "glycan_involvement": "Altered glycosylation impairs CD4-mediated immune signaling.", "mechanism": "CD4 expression linked to glycosylation disorders, impacting immune function.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "Potential glycosylation may modulate protein-protein interactions.", "mechanism": "Downregulated in pancreatitis; correlates with activated B cell and dendritic cell infiltration.", "protein": "RAP1GDS1", "protein_enriched": { "function": "Glycosyltransferase required for the biosynthesis of heparan-sulfate (HS) (PubMed:11390981). Transfers N-acetyl-alpha-D-glucosamine to the nascent HS chain (GlcNAcT-II activity) (PubMed:11390981). App", "gene_name": "EXTL1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q92935" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "No direct glycosylation reported; indirect effects possible.", "mechanism": "Downregulated in pancreatitis; correlates with activated B cell infiltration.", "protein": "TOP2A", "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Downregulated in pancreatitis; linked to activated B and CD8 T cell infiltration.", "protein": "ADK", "protein_enriched": { "function": "Catalyzes the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner. Serves as a potential regulator of concentrations of extracellular adenosine and intrace", "gene_name": "ADK", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55263" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Pancreatitis", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Downregulated in pancreatitis; associated with central memory CD4 T cell infiltration.", "protein": "POLL", "protein_enriched": { "function": "DNA polymerase that functions in several pathways of DNA repair (PubMed:11457865, PubMed:19806195, PubMed:20693240, PubMed:30250067). Involved in base excision repair (BER) responsible for repair of l", "gene_name": "POLL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UGP5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334279" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation modulates CD44-mediated cell migration and tumor microenvironment interactions.", "mechanism": "CD44 implicated in tumor progression and immune evasion under chronic hypoxia.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334279" }, { "confidence": "low", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation status influences CD44's role in PSC activation.", "mechanism": "Hypoxia-induced PSC activation affects \u03b2-cell death; CD44 involved in tissue remodeling.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12334279" }, { "confidence": "low", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation affects CD4's immune signaling in cancer.", "mechanism": "CD4 expression influences immune evasion and tumor microenvironment under hypoxia.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334279" }, { "confidence": "high", "disease": "Drug-drug interactions (DDIs)", "glycan_involvement": "Glycosylation affects Pgp stability and localization.", "mechanism": "Mediates drug efflux, affecting drug bioavailability and DDI risk.", "protein": "P-glycoprotein (Pgp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334468" }, { "confidence": "high", "disease": "Steroid-refractory acute and chronic graft versus host disease (GvHD)", "glycan_involvement": "Glycosylation modulates enzyme activity and substrate specificity.", "mechanism": "Metabolizes ruxolitinib; inhibition increases drug exposure, impacting GvHD therapy.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334468" }, { "confidence": "medium", "disease": "Drug-drug interactions (DDIs)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "UGT inhibition by piperine increases systemic exposure of co-administered drugs.", "protein": "UGT (UDP-glucuronosyltransferase)", "relationship_type": "causal", "source_pmcid": "PMC12334468" }, { "confidence": "medium", "disease": "Drug-drug interactions (DDIs)", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "SULT inhibition by piperine prolongs drug half-life, increasing DDI risk.", "protein": "SULT (Sulfotransferase)", "relationship_type": "causal", "source_pmcid": "PMC12334468" }, { "confidence": "medium", "disease": "Renal impairment", "glycan_involvement": "N-glycosylation critical for membrane localization.", "mechanism": "Inhibition alters drug clearance in renal impairment, affecting dosing.", "protein": "hOAT3 (human Organic Anion Transporter 3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334468" }, { "confidence": "medium", "disease": "Steroid-refractory acute and chronic graft versus host disease (GvHD)", "glycan_involvement": "Glycosylation influences enzyme function.", "mechanism": "Metabolizes ruxolitinib; inhibition increases drug exposure.", "protein": "CYP2C9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334468" }, { "confidence": "medium", "disease": "Drug toxicity/overdose", "glycan_involvement": "Glycosylation required for transporter function.", "mechanism": "Inhibition by piperine increases systemic drug exposure, raising toxicity risk.", "protein": "Transporters (general)", "relationship_type": "causal", "source_pmcid": "PMC12334468" }, { "confidence": "low", "disease": "Drug-drug interactions (DDIs)", "glycan_involvement": "Glycosylation modulates binding affinity.", "mechanism": "Altered binding affects free drug levels and DDI risk.", "protein": "Plasma proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12334468" }, { "confidence": "low", "disease": "Renal impairment", "glycan_involvement": "Presumed glycosylation for function.", "mechanism": "Mediates schaftoside excretion; altered in renal impairment.", "protein": "Schaftoside transporter", "relationship_type": "causal", "source_pmcid": "PMC12334468" }, { "confidence": "high", "disease": "Drug-drug interactions (DDIs)", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Metabolizes many drugs; inhibition by natural products increases DDI risk.", "protein": "CYP3A4/5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334468" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function in inflammation", "mechanism": "CRP mediates inflammation linking high salt intake to MASLD risk", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "IGF-1 is glycosylated, which influences its serum half-life and receptor interactions", "mechanism": "IGF-1 mediates metabolic dysfunction in MASLD pathogenesis", "protein": "Insulin-like growth factor-1", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "SHBG glycosylation modulates its plasma levels and hormone binding", "mechanism": "SHBG partially mediates the effect of salt intake on MASLD risk", "protein": "Sex hormone-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation of ALP affects its secretion and enzymatic activity", "mechanism": "ALP mediates liver dysfunction in MASLD progression", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation is essential for GGT stability and function", "mechanism": "GGT mediates oxidative stress and liver injury in MASLD", "protein": "Gamma-glutamyltransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity", "mechanism": "CRP levels are associated with progression to advanced fibrosis in MASLD", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "medium", "disease": "Advanced liver fibrosis", "glycan_involvement": "Glycosylation affects IGF-1 bioavailability", "mechanism": "Low IGF-1 is linked to advanced fibrosis in MASLD", "protein": "Insulin-like growth factor-1", "relationship_type": "biomarker", "source_pmcid": "PMC12334587" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "PSGL-1 function depends on O-glycosylation for P-selectin binding.", "mechanism": "Mediates adhesion of sickled RBCs and leukocytes to endothelium via P-selectin, promoting vaso-occlusion.", "protein": "P-selectin glycoprotein ligand-1 (PSGL-1)", "protein_enriched": { "function": "Plays a role in odontogenesis", "gene_name": "SSUH2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2M2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334692" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "TfR1 is N-glycosylated, which is essential for stability and function.", "mechanism": "Upregulated in SCD macrophages, indicating increased iron import and dysregulated iron metabolism.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "biomarker", "source_pmcid": "PMC12334692" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "CD86 is N-glycosylated, affecting immune synapse formation.", "mechanism": "Elevated in SCD macrophages, marking M1 pro-inflammatory polarization.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334692" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "CD206 is highly N-glycosylated, which is critical for ligand binding.", "mechanism": "Reduced in SCD macrophages, indicating decreased M2 anti-inflammatory phenotype.", "protein": "CD206 (Mannose receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12334692" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "CCR7 is N-glycosylated, influencing receptor trafficking.", "mechanism": "Increased in SCD macrophages, associated with M1 polarization and inflammation.", "protein": "CCR7", "protein_enriched": { "function": "Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions", "gene_name": "CCR7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P32248" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334692" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "FPN-1 is N-glycosylated, which affects its cell surface expression.", "mechanism": "Downregulated in SCD macrophages, leading to iron retention and contributing to inflammation.", "protein": "Ferroportin (FPN-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12334692" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "CB2 is N-glycosylated, which may modulate receptor function.", "mechanism": "Upregulated in SCD macrophages; agonist stimulation shifts macrophages to anti-inflammatory M2 phenotype and reduces pro-inflammatory cytokines.", "protein": "CB2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334692" }, { "confidence": "medium", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "TRPV1 is N-glycosylated, influencing channel function.", "mechanism": "Upregulated in SCD macrophages; agonist stimulation promotes M2 polarization and reduces inflammation.", "protein": "TRPV1", "protein_enriched": { "function": "Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:11050376, PubMed:11243859, PubMed:11226139, PubMed:12077606). Seems to mediate proto", "gene_name": "TRPV1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NER1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334692" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "O-glycans are essential for P-selectin binding.", "mechanism": "Mediates leukocyte rolling and adhesion during inflammation.", "protein": "P-selectin glycoprotein ligand-1 (PSGL-1)", "protein_enriched": { "function": "Plays a role in odontogenesis", "gene_name": "SSUH2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2M2" }, "relationship_type": "causal", "source_pmcid": "PMC12334692" }, { "confidence": "medium", "disease": "Pain (neuropathic/inflammatory)", "glycan_involvement": "N-glycosylation may affect CB2 signaling in immune cells.", "mechanism": "CB2 activation reduces neuroinflammation and pain in SCD models.", "protein": "CB2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334692" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Mannose is a key monosaccharide in N-glycosylation of glycoproteins; altered levels indicate disrupted glycosylation.", "mechanism": "Elevated serum mannose suggests altered glycoprotein synthesis or glycosylation in epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Refractory epilepsy", "glycan_involvement": "Altered glycoprotein glycosylation may affect protein stability and function in refractory epilepsy.", "mechanism": "Increased mannose may reflect persistent glycosylation changes in drug-resistant epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation changes can modulate neuronal glycoprotein function.", "mechanism": "Disrupted glycosylation inferred from elevated mannose may contribute to altered cell signaling in epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Focal epilepsy", "glycan_involvement": "Glycosylation changes may underlie subtype-specific metabolic profiles.", "mechanism": "Metabolic signatures including altered glycoprotein-related metabolites distinguish focal epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "FBTC", "glycan_involvement": "Potential involvement of glycoprotein glycosylation in seizure type specificity.", "mechanism": "Distinct metabolic profiles, possibly including glycoprotein alterations, differentiate FBTC from focal seizures.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "Glycosylation state may change dynamically with seizure activity.", "mechanism": "Altered glycoprotein metabolism may be reflected in serum metabolite changes post-seizure.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "N-glycan biosynthesis pathway involvement.", "mechanism": "Elevated mannose as a surrogate for glycoprotein turnover in epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "Glycan modifications can modulate immune recognition.", "mechanism": "Altered glycoprotein glycosylation may contribute to immune or inflammatory responses in epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "N-glycosylation critical for protein trafficking and function.", "mechanism": "Disrupted glycoprotein glycosylation may affect blood-brain barrier or neuronal signaling.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "Altered glycan structures reflect systemic metabolic changes.", "mechanism": "Serum glycoprotein glycosylation changes may serve as a general marker of metabolic stress in epilepsy.", "protein": "Serum glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12334711" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "GDNF is a glycosylated protein; glycosylation is required for secretion and receptor binding.", "mechanism": "Promotes survival and neuroprotection of dopaminergic neurons via RET and NCAM signaling.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "WNT3A is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "WNT3A upregulation promotes development and neuroprotection of dopaminergic neurons.", "protein": "WNT3A", "relationship_type": "protective", "source_pmcid": "PMC12334742" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "NCAM is heavily glycosylated; polysialylation modulates cell-cell interactions.", "mechanism": "NCAM mediates neurite outgrowth and synaptic plasticity in response to GDNF mimetics.", "protein": "NCAM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334742" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "RET is glycosylated; glycosylation is essential for cell surface expression and signaling.", "mechanism": "RET activation by GDNF promotes dopaminergic neuron survival and differentiation.", "protein": "RET proto-oncogene", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects synaptophysin trafficking and synaptic vesicle function.", "mechanism": "Synaptophysin puncta indicate synapse formation and neuronal maturation promoted by GDNF PA.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "PSD95 is glycosylated; glycosylation may influence synaptic localization.", "mechanism": "PSD95 puncta reflect postsynaptic specialization and synaptic maturation enhanced by GDNF PA.", "protein": "PSD95", "relationship_type": "biomarker", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "DAT glycosylation regulates trafficking and function.", "mechanism": "DAT expression marks mature dopaminergic neurons; upregulated in GDNF PA-treated cultures.", "protein": "Dopamine transporter (DAT)", "protein_enriched": { "function": "Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, Pu", "gene_name": "SLC6A3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q01959" }, "relationship_type": "biomarker", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "SULT1B1 is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "Upregulation of SULT1B1 is associated with increased neuronal viability; downregulated in PD.", "protein": "SULT1B1", "protein_enriched": { "function": "Plays an important role in the process of myofiber differentiation and maturation. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ", "gene_name": "NEURL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BR09" }, "relationship_type": "protective", "source_pmcid": "PMC12334742" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "PGR is glycosylated; glycosylation may modulate receptor function.", "mechanism": "PGR upregulation confers neuroprotection in PD models.", "protein": "Progesterone receptor (PGR)", "relationship_type": "protective", "source_pmcid": "PMC12334742" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "TH is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "TH marks dopaminergic neurons; used to assess survival and maturation in GDNF PA studies.", "protein": "Tyrosine hydroxylase (TH)", "relationship_type": "biomarker", "source_pmcid": "PMC12334742" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation affects secretion and stability of Factor V.", "mechanism": "Factor V Leiden mutation increases resistance to activated protein C, promoting thrombosis.", "protein": "Factor V", "relationship_type": "causal", "source_pmcid": "PMC12334955" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation required for anticoagulant activity.", "mechanism": "Antithrombin III inhibits thrombin and factor Xa, reducing clot formation.", "protein": "Antithrombin III", "relationship_type": "protective", "source_pmcid": "PMC12334955" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation essential for secretion and function.", "mechanism": "Activated Protein C degrades Factors Va and VIIIa, limiting coagulation.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC12334955" }, { "confidence": "high", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation modulates activity and plasma half-life.", "mechanism": "Cofactor for activated Protein C, enhances anticoagulant pathway.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12334955" }, { "confidence": "medium", "disease": "Cerebral Venous Thrombosis", "glycan_involvement": "N-glycosylation influences fibrin polymerization and clot stability.", "mechanism": "Fibrinogen is converted to fibrin, forming the structural basis of thrombi.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12334955" }, { "confidence": "medium", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation regulates multimer formation and function.", "mechanism": "Promotes platelet adhesion and aggregation at sites of vascular injury.", "protein": "Von Willebrand Factor", "relationship_type": "causal", "source_pmcid": "PMC12334955" }, { "confidence": "medium", "disease": "Venous Thromboembolism", "glycan_involvement": "N-glycosylation affects activation and interaction with fibrin.", "mechanism": "Plasminogen is activated to plasmin, which degrades fibrin clots.", "protein": "Plasminogen", "relationship_type": "protective", "source_pmcid": "PMC12334955" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation of SV2A is essential for its synaptic localization and function.", "mechanism": "SV2A density reflects synaptic density, which is altered in schizophrenia and can be mapped by DSN analysis.", "protein": "Synaptic vesicle glycoprotein 2A", "relationship_type": "biomarker", "source_pmcid": "PMC12335008" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects SV2A stability and trafficking in neurons.", "mechanism": "SV2A density is reduced in demyelinating diseases, reflecting synaptic loss.", "protein": "Synaptic vesicle glycoprotein 2A", "relationship_type": "biomarker", "source_pmcid": "PMC12335008" }, { "confidence": "medium", "disease": "Parkinson disease", "glycan_involvement": "Glycosylation modulates SV2A function in neurotransmitter release.", "mechanism": "SV2A PET imaging reveals synaptic loss in Parkinson disease, which can be detected by DSN.", "protein": "Synaptic vesicle glycoprotein 2A", "relationship_type": "biomarker", "source_pmcid": "PMC12335008" }, { "confidence": "low", "disease": "Major depressive disorder", "glycan_involvement": "Glycosylation is required for proper SV2A function at the synapse.", "mechanism": "Altered SV2A density is associated with synaptic changes in depression.", "protein": "Synaptic vesicle glycoprotein 2A", "relationship_type": "biomarker", "source_pmcid": "PMC12335008" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSH is associated with increased CKD prevalence and all-cause mortality; may increase urinary protein excretion.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "FT4 is derived from thyroglobulin, a glycoprotein; glycosylation of precursor impacts hormone release.", "mechanism": "Higher FT4 levels are positively correlated with CKD prevalence and increased all-cause mortality.", "protein": "FT4", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "FT3 is derived from glycoprotein thyroglobulin; glycosylation affects hormone processing.", "mechanism": "Higher FT3 levels are protective against all-cause mortality in CKD; low FT3 is a marker of poor prognosis.", "protein": "FT3", "relationship_type": "protective", "source_pmcid": "PMC12335028" }, { "confidence": "high", "disease": "All-cause mortality in CKD", "glycan_involvement": "TSH glycosylation modulates its half-life and bioactivity.", "mechanism": "U-shaped relationship; both low and high TSH associated with increased mortality.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Reflects peripheral conversion efficiency; glycosylation of precursor proteins may affect conversion.", "mechanism": "Lower FT3/FT4 ratio is associated with higher CKD prevalence and increased mortality.", "protein": "FT3/FT4 ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "Indirect; reflects hormone sensitivity, which may be influenced by glycoprotein hormone structure.", "mechanism": "Lower TFQI FT3 (better sensitivity) is associated with reduced CKD prevalence and all-cause mortality.", "protein": "TFQI FT3", "relationship_type": "protective", "source_pmcid": "PMC12335028" }, { "confidence": "medium", "disease": "Cardiovascular mortality", "glycan_involvement": "TSH and FT4 glycosylation may affect index calculation and hormone action.", "mechanism": "TT4RI shows a non-linear (inverted U-shaped) relationship with cardiovascular mortality in CKD.", "protein": "TT4RI", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "Tg is heavily glycosylated; glycosylation is essential for hormone production.", "mechanism": "Tg levels differ between CKD and non-CKD; may reflect altered thyroid hormone synthesis.", "protein": "Thyroglobulin (Tg)", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine resid", "gene_name": "TG", "glycan_count": 1, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G64527OM" ], "uniprot_id": "P01267" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "TSH glycosylation affects its metabolic clearance and activity.", "mechanism": "TSH indices (TSHI, TT4RI) are associated with increased prevalence of kidney disorders in T2D.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "TPO is glycosylated; glycosylation may affect antigenicity and immune response.", "mechanism": "TPO antibodies (autoimmunity) are associated with increased CKD risk.", "protein": "TPO", "relationship_type": "biomarker", "source_pmcid": "PMC12335028" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation critical for ICAM-1 function and cell adhesion.", "mechanism": "Upregulated in pulmonary vascular cells, promotes leukocyte adhesion and inflammation, contributing to vascular remodeling.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation affects eNOS stability and localization.", "mechanism": "Reduced eNOS activity/expression leads to decreased NO, promoting vasoconstriction and remodeling.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12335037" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 promotes inflammation and vascular remodeling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "high", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation required for IL-6 secretion and activity.", "mechanism": "Increased IL-6 correlates with disease severity and inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "Glycosylation affects MCP-1 stability and chemotactic function.", "mechanism": "Elevated MCP-1 recruits monocytes, enhancing perivascular inflammation.", "protein": "MCP-1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation modulates fractalkine's adhesive properties.", "mechanism": "Increased fractalkine mediates leukocyte adhesion and migration.", "protein": "Fractalkine", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "MMP-9 released by inflammatory cells degrades extracellular matrix, contributing to vascular remodeling.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12335037" }, { "confidence": "low", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation essential for leptin secretion and receptor interaction.", "mechanism": "Leptin overexpression promotes inflammation and vascular remodeling.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12335037" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation modulates receptor binding and stability.", "mechanism": "Elevated endothelin-1 causes vasoconstriction and smooth muscle proliferation.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension (PAH)", "glycan_involvement": "N-glycosylation required for cell surface expression and function.", "mechanism": "Upregulated VCAM-1 enhances leukocyte adhesion and vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12335037" }, { "confidence": "high", "disease": "EBV-HLH", "glycan_involvement": "CD4 is a heavily glycosylated cell surface protein; glycosylation affects stability and immune interactions.", "mechanism": "Elevated CD4\u207a T cell counts and increased CD4\u207a/CD8\u207a ratio indicate immune dysregulation and cytokine storm in EBV-HLH.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "high", "disease": "EBV-HLH", "glycan_involvement": "CD8 is glycosylated; glycosylation modulates T cell receptor interactions.", "mechanism": "Altered CD8\u207a T cell counts and CD4\u207a/CD8\u207a ratio reflect immune dysfunction and impaired cytotoxic response in EBV-HLH.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "EBV-IM", "glycan_involvement": "Glycosylation status may affect CD4 function in immune response.", "mechanism": "Lower CD4\u207a/CD8\u207a ratio in EBV-IM compared to EBV-HLH; reflects typical immune response to EBV.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "EBV-IM", "glycan_involvement": "Glycosylation influences CD8 stability and function.", "mechanism": "Higher CD8\u207a T cell activation in EBV-IM; aids in viral clearance.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "high", "disease": "EBV-HLH", "glycan_involvement": "D-dimer is a glycosylated fibrin degradation product; glycosylation affects clearance and detection.", "mechanism": "Elevated D-dimer reflects hyperfibrinolysis and coagulation dysfunction due to macrophage activation in EBV-HLH.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "high", "disease": "Thromboembolic disease", "glycan_involvement": "Glycosylation impacts D-dimer solubility and immunoreactivity.", "mechanism": "Elevated D-dimer is a marker of thromboembolic events due to increased fibrin degradation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect D-dimer half-life and detection.", "mechanism": "Persistently elevated D-dimer is associated with increased risk of cancer-related events.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "EBV-HLH", "glycan_involvement": "uPAR is a glycosylated receptor; glycosylation modulates ligand binding and cell signaling.", "mechanism": "Upregulation of uPAR on monocytes enhances local fibrinolysis, contributing to elevated D-dimer and coagulation dysfunction in EBV-HLH.", "protein": "uPAR", "relationship_type": "causal", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "EBV-HLH", "glycan_involvement": "CD25 glycosylation affects receptor stability and cytokine binding.", "mechanism": "Elevated soluble CD25 is a diagnostic criterion for HLH, reflecting T cell activation.", "protein": "Interleukin-2 receptor (CD25)", "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "medium", "disease": "MAS", "glycan_involvement": "Glycosylation influences D-dimer detection and clearance.", "mechanism": "Elevated D-dimer is an early indicator of MAS in febrile patients with active rheumatic disease.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335061" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NOTCH1 is a glycoprotein; glycosylation may affect its receptor-ligand interactions and signaling.", "mechanism": "NOTCH1 upregulation in hepatocytes promotes HCC progression by suppressing NRF2 stability via KEAP1 recruitment, leading to increased oxidative stress and ferroptosis.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation of NOTCH1 may modulate its activation and downstream signaling.", "mechanism": "Elevated NOTCH1 in hepatocytes exacerbates NASH by promoting oxidative damage and inflammation through KEAP1-NRF2 axis.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC12335071" }, { "confidence": "medium", "disease": "Hepatitis B virus infection (HBV)", "glycan_involvement": "Glycosylation status may influence NOTCH1 detection and function.", "mechanism": "NOTCH1 is upregulated in hepatocytes from HBV patients, correlating with liver injury severity.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335071" }, { "confidence": "medium", "disease": "Hepatitis C virus infection (HCV)", "glycan_involvement": "Glycosylation may affect NOTCH1 stability and localization.", "mechanism": "NOTCH1 elevation in hepatocytes is associated with HCV-induced liver injury.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Chronic liver inflammation", "glycan_involvement": "Glycosylation of NOTCH1 may regulate its signaling in inflammation.", "mechanism": "NOTCH1 promotes chronic liver inflammation by destabilizing NRF2, increasing ROS and ferroptosis.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "KEAP1 is a glycoprotein; glycosylation may affect its interaction with NOTCH1 and NRF2.", "mechanism": "KEAP1 recruited by NOTCH1 impedes KEAP1-NRF2 binding, reducing NRF2 stability and promoting HCC progression.", "protein": "KEAP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NRF2 glycosylation may influence its nuclear translocation and activity.", "mechanism": "NRF2 stability protects against oxidative stress and ferroptosis; its suppression by NOTCH1-KEAP1 axis accelerates HCC.", "protein": "NRF2", "relationship_type": "protective", "source_pmcid": "PMC12335071" }, { "confidence": "medium", "disease": "Chronic liver inflammation", "glycan_involvement": "GPX4 is glycosylated; glycan status may affect antioxidant function.", "mechanism": "GPX4 downregulation is associated with increased ferroptosis in liver injury models.", "protein": "GPX4", "relationship_type": "biomarker", "source_pmcid": "PMC12335071" }, { "confidence": "medium", "disease": "Chronic liver inflammation", "glycan_involvement": "Glycosylation may modulate ACSL4 activity.", "mechanism": "ACSL4 upregulation correlates with enhanced lipid peroxidation and ferroptosis in liver injury.", "protein": "ACSL4", "protein_enriched": { "function": "Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids ", "gene_name": "ACSL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95573" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of NOTCH1 may influence ANK domain function and therapeutic targeting.", "mechanism": "Targeting NOTCH1 ANK domain disrupts NOTCH1-KEAP1 interaction, restores NRF2 stability, and retards HCC progression.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335071" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "CRTH2 is a glycosylated GPCR; glycosylation may affect receptor function and cell surface expression.", "mechanism": "CRTH2 promotes IL-1\u03b2 production in B cells via p38 MAPK signaling, driving neuroinflammation.", "protein": "CRTH2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335081" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "IL-1\u03b2 is glycosylated, which may influence secretion and stability.", "mechanism": "IL-1\u03b2-producing B cells contribute to CNS inflammation and demyelination.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12335081" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "Glycosylation of CRTH2 may regulate its activity in B cells.", "mechanism": "CRTH2 in B cells is required for IL-1\u03b2 production and EAE severity; deletion ameliorates disease.", "protein": "CRTH2", "relationship_type": "causal", "source_pmcid": "PMC12335081" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "Glycosylation may affect IL-1\u03b2 secretion from B cells.", "mechanism": "IL-1\u03b2-producing T2 B cells drive EAE pathogenesis; deficiency protects against disease.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12335081" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "CD138 is a highly glycosylated proteoglycan; glycosylation mediates cell-cell interactions.", "mechanism": "CD138+ plasma cells produce IL-35, which is protective in EAE; not involved in IL-1\u03b2 production.", "protein": "CD138", "protein_enriched": { "function": "May act as a modulatory subunit rather than a functional channel. Unlike other P2XRs members, P2RX6 does not seem to form functional homotrimers (PubMed:22378790). P2RX6 requires the presence of P2RX4", "gene_name": "P2RX6", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "O15547" }, "relationship_type": "protective", "source_pmcid": "PMC12335081" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation may affect CRTH2 detection and function.", "mechanism": "CRTH2 expression and PGD2 metabolites are increased in SLE patients.", "protein": "CRTH2", "relationship_type": "biomarker", "source_pmcid": "PMC12335081" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "p38 MAPK signaling is upregulated in MS lesions; inhibition reduces disease severity.", "protein": "p38 MAPK", "protein_enriched": { "function": "Able to phosphorylate several exogenous substrates and to undergo autophosphorylation (PubMed:10421840). Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner (PubMed:2524", "gene_name": "Mok", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G55420XE", "G63703BK" ], "uniprot_id": "Q9WVS4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335081" }, { "confidence": "low", "disease": "Parkinson Disease", "glycan_involvement": "Glycosylation may modulate CRTH2 function in neuroinflammation.", "mechanism": "T2 B cell gene expression (regulated by CRTH2) is enriched in inflammatory pathways associated with Parkinson disease.", "protein": "CRTH2", "relationship_type": "biomarker", "source_pmcid": "PMC12335081" }, { "confidence": "low", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation may affect IL-1\u03b2 activity.", "mechanism": "IL-1\u03b2 signaling is upregulated in T2 B cells in SLE pathway enrichment.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12335081" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "CD19 is glycosylated; glycosylation may affect antibody targeting.", "mechanism": "CD19+ B cell depletion is effective in MS therapy.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335081" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SUMOylation is a PTM related to glycoprotein function, but direct glycosylation not specified for SUMO3.", "mechanism": "SUMO3 is significantly downregulated in PD; involved in SUMOylation pathways affecting \u03b1-synuclein aggregation and proteasome-mediated degradation.", "protein": "SUMO3", "protein_enriched": { "function": "Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an ", "gene_name": "SUMO3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55854" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335102" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "SUMOylation modifies glycoprotein function; direct glycosylation not specified for SEH1L.", "mechanism": "SEH1L is downregulated in PD; involved in nuclear pore function and protein degradation pathways relevant to PD.", "protein": "SEH1L", "protein_enriched": { "function": "Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC (PubMed:15146057, PubMed:17363900). The Nup107-160 ", "gene_name": "SEH1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96EE3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335102" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SUMOylation is a PTM; glycosylation status not directly discussed.", "mechanism": "SUMOylation of \u03b1-synuclein regulates its aggregation and degradation, impacting Lewy body formation.", "protein": "\u03b1-synuclein (SNCA)", "relationship_type": "causal", "source_pmcid": "PMC12335102" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "SUMOylation affects glycoprotein stability; direct glycosylation not specified.", "mechanism": "SUMOylation of DJ-1 enhances its neuroprotective function and proteasomal degradation of mitochondrial proteins.", "protein": "DJ-1 (PARK7)", "relationship_type": "protective", "source_pmcid": "PMC12335102" }, { "confidence": "medium", "disease": "Huntington's disease", "glycan_involvement": "SUMOylation as PTM; glycosylation not specified.", "mechanism": "SUMOylation implicated in neurodegeneration in HD.", "protein": "SUMO3", "protein_enriched": { "function": "Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an ", "gene_name": "SUMO3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55854" }, "relationship_type": "causal", "source_pmcid": "PMC12335102" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "SUMOylation as PTM; glycosylation not specified.", "mechanism": "Gene-disease network links SUMO3 to schizophrenia.", "protein": "SUMO3", "protein_enriched": { "function": "Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an ", "gene_name": "SUMO3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55854" }, "relationship_type": "associated", "source_pmcid": "PMC12335102" }, { "confidence": "low", "disease": "Osteoarthropathy", "glycan_involvement": "SUMOylation as PTM; glycosylation not specified.", "mechanism": "SEH1L involved in immune infiltration in osteoarthropathy.", "protein": "SEH1L", "protein_enriched": { "function": "Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC (PubMed:15146057, PubMed:17363900). The Nup107-160 ", "gene_name": "SEH1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96EE3" }, "relationship_type": "associated", "source_pmcid": "PMC12335102" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "SUMOylation as PTM; glycosylation not specified.", "mechanism": "SEH1L implicated in neurodevelopmental disorders including epilepsy.", "protein": "SEH1L", "protein_enriched": { "function": "Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC (PubMed:15146057, PubMed:17363900). The Nup107-160 ", "gene_name": "SEH1L", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96EE3" }, "relationship_type": "associated", "source_pmcid": "PMC12335102" }, { "confidence": "low", "disease": "Encephalomyelitis", "glycan_involvement": "SUMOylation as PTM; glycosylation not specified.", "mechanism": "Gene-disease network links SUMO3 to encephalomyelitis.", "protein": "SUMO3", "protein_enriched": { "function": "Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an ", "gene_name": "SUMO3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55854" }, "relationship_type": "associated", "source_pmcid": "PMC12335102" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "SUMOylation modulates glycoprotein function; direct glycosylation not specified.", "mechanism": "SUMO3 interacts with drugs (Cianidanol, Valproic acid) showing neuroprotective effects in PD models.", "protein": "SUMO3", "protein_enriched": { "function": "Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an ", "gene_name": "SUMO3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55854" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335102" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD34 is a heavily glycosylated sialomucin; glycosylation is essential for its endothelial marker function.", "mechanism": "CD34 immunostaining identifies VETC pattern, which is associated with aggressive HCC and high recurrence risk.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335122" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-1 is N-glycosylated, which affects its stability and ligand binding.", "mechanism": "Anti-PD-1 antibodies block PD-1, enhancing T cell-mediated anti-tumor immunity and improving survival.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335122" }, { "confidence": "high", "disease": "VETC-positive HCC", "glycan_involvement": "Glycosylation of PD-1 may modulate its immune checkpoint function.", "mechanism": "Anti-PD-1 therapy is especially effective in VETC-positive HCC, reducing recurrence and improving survival.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335122" }, { "confidence": "high", "disease": "VETC-positive HCC", "glycan_involvement": "Glycosylation critical for CD34's endothelial localization and detection.", "mechanism": "CD34 highlights VETC pattern, which predicts poor prognosis and high recurrence.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335122" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is glycosylated; glycoforms may affect its diagnostic utility.", "mechanism": "Elevated AFP is a risk factor for poor survival and recurrence in HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12335122" }, { "confidence": "medium", "disease": "VETC-positive HCC", "glycan_involvement": "Glycosylation patterns may differ between subtypes.", "mechanism": "Inverse relationship between VETC status and high AFP, suggesting distinct tumor subtypes.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12335122" }, { "confidence": "medium", "disease": "VETC-negative HCC", "glycan_involvement": "Glycosylation status may influence PD-1 function but not specifically addressed for this subgroup.", "mechanism": "Anti-PD-1 therapy shows limited benefit in VETC-negative HCC.", "protein": "PD-1 (Programmed cell death protein 1)", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912", "gene_name": "Pdcd1", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q02242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335122" }, { "confidence": "high", "disease": "Carbapenem-resistant gram-negative bloodstream infection", "glycan_involvement": "Glycosylation of outer membrane proteins modulates permeability and immune evasion.", "mechanism": "Altered glycoprotein structure (e.g., porin loss, glycosylation changes) reduces antibiotic entry, conferring resistance.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "high", "disease": "Multidrug-resistant gram-negative bloodstream infection", "glycan_involvement": "Altered glycosylation affects antibiotic binding and immune recognition.", "mechanism": "Glycoprotein-mediated efflux and permeability changes contribute to multidrug resistance.", "protein": "Escherichia coli outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "high", "disease": "Carbapenem-resistant gram-negative bloodstream infection", "glycan_involvement": "Glycosylation shields from host immunity and antibiotics.", "mechanism": "Surface glycoprotein modifications (including glycan changes) mediate resistance and persistence.", "protein": "Acinetobacter baumannii surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Multidrug-resistant gram-negative bloodstream infection", "glycan_involvement": "Glycosylation critical for biofilm matrix and immune evasion.", "mechanism": "Biofilm formation and glycoprotein-mediated efflux pumps drive resistance.", "protein": "Pseudomonas aeruginosa outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "O-antigen glycan structure modulates immune activation.", "mechanism": "LPS (glycolipid/glycoprotein complex) triggers systemic inflammation.", "protein": "Enterobacterales lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Hematologic malignancy-associated infection", "glycan_involvement": "Capsular polysaccharide (glycan) shields bacteria from phagocytosis.", "mechanism": "Immunocompromised hosts are susceptible to glycoprotein-mediated immune evasion.", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation patterns affect host-pathogen interactions.", "mechanism": "Surface glycoproteins contribute to immune evasion and systemic infection.", "protein": "Acinetobacter baumannii surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Carbapenem-resistant gram-negative bloodstream infection", "glycan_involvement": "Glycosylation changes alter drug permeability.", "mechanism": "Porin loss and glycoprotein modification reduce carbapenem uptake.", "protein": "Escherichia coli outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Multidrug-resistant gram-negative bloodstream infection", "glycan_involvement": "Glycosylation affects enzyme localization and function.", "mechanism": "Glycoprotein-mediated resistance mechanisms (e.g., ESBL, carbapenemase production).", "protein": "Klebsiella pneumoniae outer membrane proteins", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "medium", "disease": "Multidrug-resistant gram-negative bloodstream infection", "glycan_involvement": "O-antigen glycan length and composition modulate resistance.", "mechanism": "LPS structure contributes to antibiotic resistance and immune evasion.", "protein": "Enterobacterales lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12335129" }, { "confidence": "high", "disease": "acute kidney injury (AKI)", "glycan_involvement": "megalin is a heavily glycosylated receptor; glycosylation affects ligand binding and trafficking.", "mechanism": "Colistin binds to megalin on proximal tubular cells, mediating reabsorption and intracellular accumulation, leading to mitochondrial damage and apoptosis.", "protein": "megalin", "relationship_type": "causal", "source_pmcid": "PMC12335134" }, { "confidence": "high", "disease": "nephrotoxicity", "glycan_involvement": "CMS is a glycopeptide prodrug; glycosylation affects renal handling and toxicity.", "mechanism": "CMS is converted to colistin in vivo, which accumulates in renal tubular cells and causes nephrotoxicity.", "protein": "colistimethate sodium (CMS)", "relationship_type": "causal", "source_pmcid": "PMC12335134" }, { "confidence": "high", "disease": "acute kidney injury (AKI)", "glycan_involvement": "Colistin interacts with glycoprotein receptors (megalin); glycosylation modulates uptake.", "mechanism": "Colistin directly damages renal tubular epithelial cells via membrane disruption and apoptosis.", "protein": "colistin (polymyxin E)", "relationship_type": "causal", "source_pmcid": "PMC12335134" }, { "confidence": "medium", "disease": "acute kidney injury (AKI)", "glycan_involvement": "Albumin glycosylation status may affect its protective role and pharmacokinetics.", "mechanism": "Low serum albumin is associated with increased risk of AKI in colistin-treated patients.", "protein": "albumin", "relationship_type": "protective", "source_pmcid": "PMC12335134" }, { "confidence": "medium", "disease": "sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP is a marker of inflammation and sepsis severity in patients receiving polymyxins.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335134" }, { "confidence": "low", "disease": "liver dysfunction", "glycan_involvement": "AST is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Elevated AST is used to monitor liver function in patients treated with polymyxins.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12335134" }, { "confidence": "low", "disease": "hematologic malignancy", "glycan_involvement": "IgG glycosylation modulates immune response and disease progression.", "mechanism": "Altered IgG levels are associated with hematologic malignancies in the patient cohort.", "protein": "immunoglobulin G (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12335134" }, { "confidence": "low", "disease": "sepsis", "glycan_involvement": "Surface glycoproteins mediate immune cell interactions; glycosylation affects function.", "mechanism": "WBC count is used to assess infection and sepsis severity.", "protein": "white blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12335134" }, { "confidence": "low", "disease": "acute kidney injury (AKI)", "glycan_involvement": "V2R is glycosylated; glycosylation affects receptor signaling.", "mechanism": "Vasopressors are associated with increased AKI risk in polymyxin-treated patients.", "protein": "vasopressin receptor (V2R)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12335134" }, { "confidence": "medium", "disease": "chronic kidney disease", "glycan_involvement": "Glycosylation of CMS affects renal excretion and toxicity.", "mechanism": "High cumulative CMS dose (>5g) is an independent predictor of progression to chronic kidney disease.", "protein": "colistimethate sodium (CMS)", "relationship_type": "causal", "source_pmcid": "PMC12335134" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "ALP is elevated in osteoporosis, reflecting increased bone turnover.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335165" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "CRP glycosylation modulates its function and clearance.", "mechanism": "CRP is elevated in osteoporosis, indicating systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335165" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "LDH is glycosylated, which may affect its serum levels.", "mechanism": "LDH is increased in osteoporosis, reflecting tissue turnover.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335165" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "AST is a glycoprotein; glycosylation may influence its activity.", "mechanism": "AST is elevated in osteoporosis, possibly reflecting bone or liver involvement.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335165" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "ALT glycosylation may affect its serum stability.", "mechanism": "ALT is increased in osteoporosis, possibly reflecting metabolic changes.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335165" }, { "confidence": "high", "disease": "Rectal cancer", "glycan_involvement": "Associated with upregulation of glycosyltransferases and aberrant glycosylation.", "mechanism": "High MS4A12 expression correlates with advanced tumor stage, poor response to CCRT, and inferior survival.", "protein": "MS4A12", "protein_enriched": { "function": "The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type", "gene_name": "CACNA2D3", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8IZS8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335166" }, { "confidence": "high", "disease": "Chemoradiotherapy resistance", "glycan_involvement": "Linked to increased expression of glycosyltransferases involved in glycan biosynthesis.", "mechanism": "High MS4A12 marks resistance to neoadjuvant CCRT in rectal cancer.", "protein": "MS4A12", "protein_enriched": { "function": "The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type", "gene_name": "CACNA2D3", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8IZS8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335166" }, { "confidence": "high", "disease": "Poor survival in rectal cancer", "glycan_involvement": "Aberrant glycosylation may contribute to aggressive phenotype.", "mechanism": "High MS4A12 independently predicts reduced disease-specific, recurrence-free, and metastasis-free survival.", "protein": "MS4A12", "protein_enriched": { "function": "The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type", "gene_name": "CACNA2D3", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8IZS8" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Rectal cancer", "glycan_involvement": "MUC2 is a heavily O-glycosylated mucin forming a physical barrier.", "mechanism": "High MUC2 expression is an adverse prognostic factor for rectal cancer patients undergoing CCRT.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Metastasis in cancer", "glycan_involvement": "Mediates type I chain synthesis via galactosylation.", "mechanism": "High B3GALT1 expression is associated with high metastatic potential in hepatocarcinoma and drug resistance in breast cancer.", "protein": "B3GALT1", "relationship_type": "causal", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Involved in galactosylation of glycoproteins.", "mechanism": "High B3GALT5 correlates with poor relapse-free and overall survival.", "protein": "B3GALT5", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "Catalyzes final step in Sda/Cad antigen synthesis (O-glycosylation).", "mechanism": "High B4GALNT2 expression linked to good prognosis in colon cancer.", "protein": "B4GALNT2", "protein_enriched": { "function": "Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity)", "gene_name": "NBEA", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G32392SM", "G49108TO", "G37399XV", "G28681TP", "G75230KT" ], "uniprot_id": "Q8NFP9" }, "relationship_type": "protective", "source_pmcid": "PMC12335166" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Adds sialic acid to GalNAc residues (O-glycosylation).", "mechanism": "ST6GALNAC1 promotes sialyl-Tn antigen expression, associated with poor prognosis and 5-FU resistance.", "protein": "ST6GALNAC1", "protein_enriched": { "function": "The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable ", "gene_name": "BBS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3SYG4" }, "relationship_type": "causal", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Sialylation of O-glycans on glycoproteins.", "mechanism": "ST6GALNAC1 confers cisplatin and 5-FU resistance.", "protein": "ST6GALNAC1", "protein_enriched": { "function": "The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable ", "gene_name": "BBS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3SYG4" }, "relationship_type": "causal", "source_pmcid": "PMC12335166" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Prefers sialylation of glycolipids over glycoproteins.", "mechanism": "ST6GALNAC6 expression in stromal cells suppresses T-cell activation, promoting immune evasion.", "protein": "ST6GALNAC6", "relationship_type": "causal", "source_pmcid": "PMC12335166" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Fc glycosylation modulates antibody effector function", "mechanism": "Blocks PD-L1, enhancing T cell-mediated anti-tumor immunity", "protein": "Durvalumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Fc glycosylation affects antibody stability and immune activation", "mechanism": "Blocks CTLA-4, promoting T cell activation against tumor", "protein": "Tremelimumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335178" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects antibody binding", "mechanism": "PD-L1 on tumor cells inhibits T cell function; blockade restores immunity", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335178" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates PD-1 stability and ligand interaction", "mechanism": "PD-1 on T cells mediates immune suppression; blockade enhances response", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335178" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation required for CTLA-4 surface expression", "mechanism": "CTLA-4 inhibits T cell activation; blockade increases anti-tumor immunity", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335178" }, { "confidence": "high", "disease": "Immune-mediated hepatitis", "glycan_involvement": "Fc glycosylation may influence immune effector functions", "mechanism": "Immune checkpoint blockade leads to T cell-mediated liver injury", "protein": "Durvalumab", "relationship_type": "causal", "source_pmcid": "PMC12335178" }, { "confidence": "high", "disease": "Immune-mediated enterocolitis", "glycan_involvement": "Fc glycosylation may modulate antibody-mediated immune activation", "mechanism": "CTLA-4 inhibition disrupts gut immune tolerance, causing colitis", "protein": "Tremelimumab", "relationship_type": "causal", "source_pmcid": "PMC12335178" }, { "confidence": "medium", "disease": "Immune-mediated myocarditis", "glycan_involvement": "Fc glycosylation may affect immune cell recruitment", "mechanism": "PD-L1 blockade triggers T cell attack on cardiac tissue", "protein": "Durvalumab", "relationship_type": "causal", "source_pmcid": "PMC12335178" }, { "confidence": "medium", "disease": "Immune-mediated dermatitis", "glycan_involvement": "Fc glycosylation may influence skin inflammation", "mechanism": "Immune checkpoint inhibition leads to skin-directed autoimmunity", "protein": "Durvalumab", "relationship_type": "causal", "source_pmcid": "PMC12335178" }, { "confidence": "medium", "disease": "Immune-mediated adrenal insufficiency", "glycan_involvement": "Fc glycosylation may modulate immune effector function", "mechanism": "Immune activation damages adrenal tissue", "protein": "Durvalumab", "relationship_type": "causal", "source_pmcid": "PMC12335178" }, { "confidence": "high", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "KLB is a glycoprotein; glycosylation may affect stability and shedding, but specific glycan changes not detailed.", "mechanism": "Serum \u03b2-klotho (sKLB) levels are significantly elevated in ALD, reflecting hepatocellular injury and FGF21/FGF19 signaling changes.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "KLB glycosylation may influence secretion; specific glycan changes not described.", "mechanism": "sKLB levels are significantly reduced in NAFLD, likely due to transcriptional repression, epigenetic modification, and genetic variants.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Alcoholic cirrhosis (AC)", "glycan_involvement": "Glycosylation may affect sKLB stability and release; not specifically addressed.", "mechanism": "sKLB levels increase progressively with ALD severity, highest in cirrhosis and liver failure.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Alcoholic liver failure (ALF)", "glycan_involvement": "As above; glycosylation may modulate shedding.", "mechanism": "sKLB levels tend to be highest in ALF, suggesting correlation with disease severity.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Glycosylation may affect receptor function and FGF21 signaling.", "mechanism": "Upregulation of intestinal KLB mitigates ethanol-induced liver damage and inflammation via gut-liver axis modulation.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "protective", "source_pmcid": "PMC12335235" }, { "confidence": "high", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "GGT is glycosylated; glycosylation affects stability and activity.", "mechanism": "Serum GGT is elevated in ALD due to hepatocellular damage and enzyme leakage.", "protein": "\u03b3-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "high", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "AST is glycosylated; glycosylation may affect serum levels.", "mechanism": "AST/ALT ratio is increased in ALD due to mitochondrial damage and pyridoxine deficiency.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Genetic variant may affect glycosylation and protein stability.", "mechanism": "KLB rs17618244 polymorphism reduces hepatic KLB expression, associated with increased NAFLD severity (fibrosis, inflammation).", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "causal", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Glycosylation may influence sKLB detection and function.", "mechanism": "sKLB positively correlates with markers of cholestasis and fibrosis (TBIL, TBA, HA, CIV), indicating disease severity.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "medium", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Glycosylation may affect sKLB secretion and function.", "mechanism": "sKLB negatively correlates with HDL, suggesting involvement in dysregulated lipid metabolism during ALD.", "protein": "\u03b2-klotho (KLB)", "protein_enriched": { "function": "Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of", "gene_name": "KLB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G74724QE", "G62765YT", "G64409MC", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q86Z14" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335235" }, { "confidence": "high", "disease": "COPD-associated pulmonary fibrosis", "glycan_involvement": "TFR1 is a glycoprotein; glycosylation is required for its cell surface expression and function.", "mechanism": "Serum TFR1 levels positively correlate with fibrosis score and severity of pulmonary fibrosis in COPD patients.", "protein": "TFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation maintains TFR1 stability and iron transport activity.", "mechanism": "Higher serum TFR1 levels are associated with increased GOLD grade, more frequent acute exacerbations, and worse lung function.", "protein": "TFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation may affect TFR1's interaction with transferrin and iron uptake.", "mechanism": "Targeting TFR1 may prevent ferroptosis and progression of fibrosis in COPD.", "protein": "TFR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335247" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation required for TFR1 surface expression.", "mechanism": "High TFR1 expression in BALF correlates with impaired lung function and asthma severity.", "protein": "TFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation essential for TFR1-mediated signaling.", "mechanism": "TFR1 promotes airway inflammation and mucus cell proliferation via ferroptosis pathway.", "protein": "TFR1", "relationship_type": "causal", "source_pmcid": "PMC12335247" }, { "confidence": "high", "disease": "Pulmonary fibrosis", "glycan_involvement": "COL3 is glycosylated, which affects its secretion and matrix assembly.", "mechanism": "Serum COL3 levels correlate with fibrosis score and frequency of acute exacerbation in COPD.", "protein": "COL3", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "high", "disease": "COPD-associated lung injury", "glycan_involvement": "Glycosylation required for TFR1 function in iron uptake.", "mechanism": "TFR1 levels in plasma and BALF correlate with degree of lung injury in mouse COPD models.", "protein": "TFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Glycosylation may modulate TFR1's susceptibility to inhibition.", "mechanism": "Inhibition of TFR1 may reduce ferroptosis and lung injury in COPD.", "protein": "TFR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335247" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation required for TFR1 macrophage function.", "mechanism": "TFR1+ macrophages contribute to fibrosis via ferroptosis; DFO treatment reduces injury by inhibiting ferroptosis.", "protein": "TFR1", "relationship_type": "causal", "source_pmcid": "PMC12335247" }, { "confidence": "high", "disease": "COPD-associated pulmonary fibrosis", "glycan_involvement": "Glycosylation ensures TFR1 stability in serum.", "mechanism": "Serum TFR1 outperforms COL3 and fibrosis score in predicting acute exacerbation frequency.", "protein": "TFR1", "relationship_type": "biomarker", "source_pmcid": "PMC12335247" }, { "confidence": "high", "disease": "Sarcopenia/muscle weakness", "glycan_involvement": "Adiponectin is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "Suppressed Adipoq expression in muscle correlates with reduced intermuscular adipose tissue and improved muscle strength.", "protein": "Adiponectin (Adipoq)", "protein_enriched": { "function": "", "gene_name": "tat", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q3S5G7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "high", "disease": "Sarcopenia/muscle weakness", "glycan_involvement": "Fabp4 is glycosylated; glycosylation may affect stability and function.", "mechanism": "Reduced Fabp4 expression in muscle is associated with less intramuscular fat and improved muscle function.", "protein": "Fatty acid-binding protein 4 (Fabp4)", "protein_enriched": { "function": "Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus", "gene_name": "Fabp4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04117" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Upregulation of Sirt1 in muscle enhances mitochondrial biogenesis and energy expenditure, contributing to anti-obesity effects.", "protein": "Sirtuin 1 (Sirt1)", "protein_enriched": { "function": "NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell c", "gene_name": "SIRT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96EB6" }, "relationship_type": "protective", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Sarcopenia/muscle weakness", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Increased Sirt1 expression improves mitochondrial function and muscle strength.", "protein": "Sirtuin 1 (Sirt1)", "protein_enriched": { "function": "NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell c", "gene_name": "SIRT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96EB6" }, "relationship_type": "protective", "source_pmcid": "PMC12335443" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Elevated p16INK4a expression marks hepatic senescence and NAFLD progression; downregulation indicates disease mitigation.", "protein": "Cyclin-dependent kinase inhibitor 2A (p16INK4a)", "protein_enriched": { "function": "Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest", "gene_name": "CDKN2B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P42772" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Collagen is glycosylated; glycosylation affects fibril formation and fibrosis.", "mechanism": "Upregulation of Col1a1 indicates liver fibrosis in NAFLD.", "protein": "Collagen type I alpha 1 (Col1a1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Collagen is glycosylated; glycosylation affects structure and fibrosis.", "mechanism": "Upregulation of Col3a1 is associated with liver fibrosis in NAFLD.", "protein": "Collagen type III alpha 1 (Col3a1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Upregulation of Cidea is linked to hepatic lipid accumulation and NAFLD progression.", "protein": "Cell death-inducing DFFA-like effector A (Cidea)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z0K1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "TNF\u03b1 is glycosylated; glycosylation modulates secretion and activity.", "mechanism": "Elevated Tnf\u03b1 indicates hepatic inflammation in NAFLD.", "protein": "Tumor necrosis factor alpha (Tnf\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12335443" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Fabp4 glycosylation may affect its metabolic role.", "mechanism": "Downregulation of Fabp4 improves insulin sensitivity in muscle.", "protein": "Fatty acid-binding protein 4 (Fabp4)", "protein_enriched": { "function": "Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus", "gene_name": "Fabp4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04117" }, "relationship_type": "causal", "source_pmcid": "PMC12335443" }, { "confidence": "high", "disease": "Coronary microvascular dysfunction", "glycan_involvement": "PLIN2 is glycosylated, affecting LD stability and autophagic degradation.", "mechanism": "PLIN2 upregulation marks increased LD biogenesis in endothelial cells under lipotoxic stress.", "protein": "PLIN2", "relationship_type": "biomarker", "source_pmcid": "PMC12335489" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation critical for LAMP2A lysosomal targeting and function.", "mechanism": "LAMP2A mediates chaperone-mediated autophagy of PLIN2, regulating LD catabolism and cellular lipid homeostasis.", "protein": "LAMP2A", "relationship_type": "causal", "source_pmcid": "PMC12335489" }, { "confidence": "high", "disease": "ER stress-related injury", "glycan_involvement": "N-glycosylation modulates chaperone activity and ER localization.", "mechanism": "GRP78/BIP upregulation indicates ER stress in endothelial cells exposed to oleic acid.", "protein": "GRP78/BIP (HSPA5)", "relationship_type": "biomarker", "source_pmcid": "PMC12335489" }, { "confidence": "high", "disease": "Ferroptosis-related cell death", "glycan_involvement": "GPX4 glycosylation may affect stability and activity (not directly shown here).", "mechanism": "GPX4 prevents lipid peroxide accumulation and ferroptosis; its inhibition or downregulation triggers cell death.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12335489" }, { "confidence": "medium", "disease": "Lipotoxicity", "glycan_involvement": "SREBP1 glycosylation regulates ER retention and activation.", "mechanism": "SREBP1 nuclear levels reflect fatty acid biosynthesis activity and adaptation to lipid overload.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335489" }, { "confidence": "high", "disease": "ER stress-related injury", "glycan_involvement": "Glycosylation may affect CHOP stability (not directly shown here).", "mechanism": "CHOP induction marks severe ER stress and impending cell death in endothelial cells.", "protein": "CHOP (DDIT3)", "relationship_type": "biomarker", "source_pmcid": "PMC12335489" }, { "confidence": "medium", "disease": "Hypoxia-induced vascular injury", "glycan_involvement": "O-glycosylation modulates HIF-1\u03b1 stability and transcriptional activity.", "mechanism": "HIF-1\u03b1 activation drives pseudohypoxic response, glycolysis, and LD biogenesis under mitochondrial dysfunction.", "protein": "HIF-1\u03b1", "protein_enriched": { "function": "Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:206249", "gene_name": "HIF1A", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G65000LJ", "G49108TO" ], "uniprot_id": "Q16665" }, "relationship_type": "causal", "source_pmcid": "PMC12335489" }, { "confidence": "medium", "disease": "Ferroptosis-related cell death", "glycan_involvement": "Glycosylation affects iron storage function.", "mechanism": "FTH1 upregulation is an adaptive response to iron overload and ferroptosis.", "protein": "FTH1", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role ", "gene_name": "Ftl1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29391" }, "relationship_type": "protective", "source_pmcid": "PMC12335489" }, { "confidence": "medium", "disease": "Ferroptosis-related cell death", "glycan_involvement": "Glycosylation modulates enzyme activity and cellular localization.", "mechanism": "HMOX1 activation can be protective (ROS scavenging) or promote ferroptosis (iron release) depending on activation level.", "protein": "HMOX1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "HMOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09601" }, "relationship_type": "dual (protective/causal)", "source_pmcid": "PMC12335489" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation essential for LAMP2A function in autophagy.", "mechanism": "Defective LAMP2A-mediated autophagy impairs LD catabolism, contributing to lipid accumulation and vascular inflammation.", "protein": "LAMP2A", "relationship_type": "causal", "source_pmcid": "PMC12335489" }, { "confidence": "high", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "CPS is a glycan-rich surface structure; glycosylation is essential for its protective function.", "mechanism": "CPS enhances bacterial survival under high-fat diet-induced stress, co-selecting for ARGs and virulence traits.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Colonic tumorigenesis", "glycan_involvement": "Glycosylation of CPS is critical for immune evasion and persistence.", "mechanism": "CPS-producing bacteria persist under high-fat diet, contributing to inflammation and carcinogenesis.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation may modulate effector function and host interaction.", "mechanism": "High-fat diet increases abundance of secretion system effectors, correlating with increased virulence and ARGs.", "protein": "Type III secretion system effectors", "relationship_type": "biomarker", "source_pmcid": "PMC12335491" }, { "confidence": "high", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Potential glycosylation of resistance proteins may affect stability/function.", "mechanism": "High-fat diet increases vancomycin resistance gene abundance, promoting AMR.", "protein": "Vancomycin resistance proteins (vanD, vanG, vanR, vanS)", "relationship_type": "causal", "source_pmcid": "PMC12335491" }, { "confidence": "high", "disease": "Nosocomial infections (ESKAPE pathogens)", "glycan_involvement": "Glycosylation may influence enzyme secretion and activity.", "mechanism": "High-fat diet and obesity increase beta-lactamase gene abundance in Klebsiella, raising infection risk.", "protein": "Beta-lactamase (bla SHV, bla TME-136, bla TME-127)", "relationship_type": "biomarker", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Nosocomial infections (ESKAPE pathogens)", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Klebsiella carrying fosA is more abundant in high-fat/obese individuals, increasing resistance risk.", "protein": "Fosfomycin resistance protein (fosA)", "relationship_type": "biomarker", "source_pmcid": "PMC12335491" }, { "confidence": "high", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation may modulate protein function.", "mechanism": "High-fat diet increases tetracycline resistance genes in Enterococcus and Staphylococcus.", "protein": "Tetracycline resistance proteins (tetM, tetL, tetW)", "relationship_type": "causal", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Possible glycosylation effects on protein function.", "mechanism": "lsa gene abundance is higher in high-fat diet/obesity, indicating increased resistance.", "protein": "Pleuromutilin\u2013lincosamide\u2013streptogramin A resistance protein (lsa)", "relationship_type": "biomarker", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Potential glycosylation involvement.", "mechanism": "fexB gene is more abundant in Enterococcus in high-fat/obese individuals.", "protein": "Florfenicol resistance protein (fexB)", "relationship_type": "biomarker", "source_pmcid": "PMC12335491" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "CPS glycosylation is essential for barrier formation.", "mechanism": "CPS protects bacteria from bile acids and immune attack, contributing to barrier dysfunction under high-fat diet.", "protein": "Capsular polysaccharide (CPS)", "relationship_type": "causal", "source_pmcid": "PMC12335491" }, { "confidence": "high", "disease": "Hepato-pancreato-biliary cancers (general)", "glycan_involvement": "CEA is a heavily N-glycosylated glycoprotein; glycosylation affects its serum stability and detection.", "mechanism": "CEA is elevated in serum of HPB cancer patients and used for diagnosis/monitoring.", "protein": "Carcinoembryonic antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Cholangiocarcinoma", "glycan_involvement": "CA19-9 is a sialylated Lewis antigen (glycan epitope) present on glycoproteins/lipids.", "mechanism": "CA19-9 is elevated in CCA and used for diagnosis, but lacks specificity.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "Glycan epitope; sialylation and fucosylation are critical for antigenicity.", "mechanism": "CA19-9 is elevated in PDAC and used for diagnosis, but also elevated in benign conditions.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is N-glycosylated; glycoforms may affect detection and disease association.", "mechanism": "AFP is elevated in HCC and used for diagnosis, but with limited sensitivity/specificity.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Hepato-pancreato-biliary cancers (general)", "glycan_involvement": "Many serum peptides are glycosylated; altered glycosylation in cancer changes peptide profiles.", "mechanism": "Serum PMFs (including glycopeptides) distinguish HPB cancers from healthy controls with high accuracy.", "protein": "Peptide mass fingerprint (PMF) panel", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Cholangiocarcinoma", "glycan_involvement": "Altered glycosylation patterns in CCA affect serum peptide/glycopeptide composition.", "mechanism": "Distinct PMF signatures enable discrimination of CCA from other HPB cancers.", "protein": "Peptide mass fingerprint (PMF) panel", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Cancer-associated glycosylation changes reflected in serum peptide/glycopeptide patterns.", "mechanism": "PMF profiles allow accurate classification of HCC among HPB cancers.", "protein": "Peptide mass fingerprint (PMF) panel", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Altered glycosylation in GBC impacts serum peptide/glycopeptide profiles.", "mechanism": "PMF signatures can distinguish GBC from other HPB cancers, though with lower sensitivity.", "protein": "Peptide mass fingerprint (PMF) panel", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "PDAC-associated glycosylation changes alter serum glycopeptide patterns.", "mechanism": "PMF profiles differentiate PDAC from other HPB cancers.", "protein": "Peptide mass fingerprint (PMF) panel", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "medium", "disease": "Gallbladder cancer", "glycan_involvement": "Glycan epitope; glycosylation state affects antigen detection.", "mechanism": "CA19-9 is elevated in GBC but lacks specificity for this cancer type.", "protein": "Carbohydrate antigen 19-9", "relationship_type": "biomarker", "source_pmcid": "PMC12335492" }, { "confidence": "high", "disease": "Monkeypox (Mpox)", "glycan_involvement": "Glycosylation likely mediates immune recognition and viral egress.", "mechanism": "A35R is an EEV envelope glycoprotein critical for cell-to-cell spread; antibody targeting confers protection.", "protein": "A35R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335498" }, { "confidence": "high", "disease": "Monkeypox (Mpox)", "glycan_involvement": "Glycosylation may affect receptor binding and immunogenicity.", "mechanism": "A29L is an IMV surface glycoprotein mediating viral attachment; antibodies neutralize infection.", "protein": "A29L", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335498" }, { "confidence": "high", "disease": "Monkeypox (Mpox)", "glycan_involvement": "Glycosylation may influence folding and immune recognition.", "mechanism": "L1R is an IMV surface glycoprotein essential for viral morphogenesis; antibody targeting inhibits infection.", "protein": "L1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335498" }, { "confidence": "high", "disease": "Monkeypox (Mpox)", "glycan_involvement": "Glycosylation mediates B-cell epitope presentation.", "mechanism": "A33R (VACV homolog of A35R) is an EEV glycoprotein; cross-reactive antibodies provide protection.", "protein": "A33R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335498" }, { "confidence": "medium", "disease": "Monkeypox (Mpox)", "glycan_involvement": "Glycosylation may modulate host cell interaction.", "mechanism": "A27L (VACV homolog of A29L) is an IMV glycoprotein mediating attachment to heparan sulfate; antibody targeting blocks entry.", "protein": "A27L", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335498" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "Antibodies against A35R cross-neutralize VACV, reducing viral load.", "protein": "A35R", "relationship_type": "protective", "source_pmcid": "PMC12335498" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Glycosylation may affect cross-reactivity.", "mechanism": "Antibodies against A29L cross-neutralize VACV.", "protein": "A29L", "relationship_type": "protective", "source_pmcid": "PMC12335498" }, { "confidence": "medium", "disease": "Monkeypox (Mpox)", "glycan_involvement": "N-glycosylation required for surface expression and function.", "mechanism": "Upregulation on dendritic cells indicates vaccine-induced maturation and immune activation.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335498" }, { "confidence": "medium", "disease": "Monkeypox (Mpox)", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Upregulation on dendritic cells reflects immune activation post-vaccination.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335498" }, { "confidence": "medium", "disease": "Monkeypox (Mpox)", "glycan_involvement": "N-glycosylation essential for peptide loading and surface expression.", "mechanism": "Increased expression on dendritic cells correlates with antigen presentation and T-cell activation.", "protein": "MHC I/II", "relationship_type": "biomarker", "source_pmcid": "PMC12335498" }, { "confidence": "high", "disease": "Inflammatory disorders", "glycan_involvement": "N-glycosylation of COX-2 affects its stability and localization, influencing inflammatory signaling.", "mechanism": "COX-2 is upregulated during inflammation; inhibition reduces prostaglandin synthesis and inflammation.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335560" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "N-glycosylation modulates COX-2 activity in arthritic tissues.", "mechanism": "COX-2 inhibition by NSAIDs (e.g., flurbiprofen derivatives) reduces joint inflammation and pain.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335560" }, { "confidence": "medium", "disease": "Pain", "glycan_involvement": "Glycosylation may affect COX-2's interaction with other pain mediators.", "mechanism": "COX-2-derived prostaglandins sensitize pain pathways; inhibition alleviates pain.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335560" }, { "confidence": "low", "disease": "Gastrointestinal toxicity", "glycan_involvement": "Glycosylation status may influence COX-2 selectivity and tissue distribution.", "mechanism": "Non-selective COX inhibition (COX-1/COX-2) by NSAIDs leads to GI toxicity; selective COX-2 inhibition reduces this risk.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "causal", "source_pmcid": "PMC12335560" }, { "confidence": "medium", "disease": "Inflammatory disorders", "glycan_involvement": "N-glycosylation is critical for P-gp trafficking and function.", "mechanism": "P-gp limits drug absorption and distribution; non-substrate status of new derivatives may enhance anti-inflammatory efficacy.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective", "source_pmcid": "PMC12335560" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure", "glycan_involvement": "N-glycosylation affects NT-proBNP stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac wall stress and severity of heart failure.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "N-glycosylation modulates transferrin half-life and receptor binding.", "mechanism": "Low transferrin saturation indicates iron deficiency, common in heart failure.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycosylation influences ferritin secretion and immune recognition.", "mechanism": "Elevated ferritin reflects inflammation and iron status; associated with prolonged hospitalization.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycosylation affects procalcitonin serum levels.", "mechanism": "Elevated procalcitonin indicates systemic inflammation/infection, predicting longer hospital stay.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Minor O-glycosylation may affect hemoglobin function in disease.", "mechanism": "Low hemoglobin is associated with anemia, a risk factor for prolonged hospitalization.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure", "glycan_involvement": "LDL receptor N-glycosylation is essential for function and statin response.", "mechanism": "Prior statin use is protective against prolonged hospitalization.", "protein": "Statins (target: LDL receptor)", "relationship_type": "protective", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure", "glycan_involvement": "N-glycosylation modulates SGLT2 trafficking and activity.", "mechanism": "SGLT2 inhibitors are part of heart failure therapy; glycosylation affects transporter function.", "protein": "Sodium-Glucose Cotransporter 2 (SGLT2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335576" }, { "confidence": "medium", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycosylation affects CRP's immunological activity.", "mechanism": "CRP is elevated in inflammation and predicts adverse outcomes in heart failure.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "low", "disease": "Prolonged Hospitalization", "glycan_involvement": "Minor N-glycosylation may affect albumin's half-life.", "mechanism": "Low albumin (hypoalbuminemia) is associated with worse prognosis and longer hospital stay.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "low", "disease": "Iron Deficiency", "glycan_involvement": "N-glycosylation is critical for receptor function.", "mechanism": "Transferrin receptor levels reflect iron status and erythropoiesis in heart failure.", "protein": "Transferrin Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12335576" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "PD-L1 is heavily N-glycosylated, which stabilizes its cell surface expression and affects antibody binding.", "mechanism": "PD-L1 expression on tumor cells suppresses T cell activity; blockade restores antitumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma", "glycan_involvement": "PD-1 glycosylation modulates ligand binding and receptor stability.", "mechanism": "PD-1 on T cells binds PD-L1/PD-L2, leading to immune evasion; inhibitors restore T cell function.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "CTLA-4 is N-glycosylated, affecting its trafficking and surface expression.", "mechanism": "CTLA-4 competes with CD28 for B7 ligands, inhibiting T cell activation; blockade enhances immune response.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Esophageal Cancer", "glycan_involvement": "LAG-3 is glycosylated, which may affect ligand binding.", "mechanism": "LAG-3 inhibits T cell function via interaction with ligands (e.g., galectin-3, FGL1); blockade enhances antitumor immunity.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "TIM-3 palmitoylation and glycosylation stabilize the protein and regulate degradation.", "mechanism": "TIM-3 on T cells interacts with galectin-9, leading to T cell exhaustion; inhibition reverses immune suppression.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "TIGIT is glycosylated, influencing ligand interactions.", "mechanism": "TIGIT suppresses T cell and NK cell activity via binding to CD155/CD112; blockade enhances antitumor immunity.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "VISTA is a glycoprotein; glycosylation may affect immune modulation.", "mechanism": "VISTA suppresses T cell activation; monoclonal antibodies targeting VISTA are in clinical trials.", "protein": "VISTA", "protein_enriched": { "function": "Cell surface glycoprotein involved in various biological processes including angiogenesis, immune response modulation, and tissue remodeling and repair. Participates in pericyte proliferation through ", "gene_name": "CD248", "glycan_count": 5, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57317CE", "G49108TO" ], "uniprot_id": "Q9HCU0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma", "glycan_involvement": "B7-H3 is glycosylated, which may affect antibody recognition.", "mechanism": "B7-H3 overexpression promotes immune evasion; antibody therapy shows antitumor effects.", "protein": "B7-H3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "B7-H4 is glycosylated, influencing its function and drug targeting.", "mechanism": "B7-H4 expression is linked to platinum and PARPi resistance; antibody-drug conjugates inhibit tumor growth.", "protein": "B7-H4", "protein_enriched": { "function": "Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor ma", "gene_name": "VTCN1", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G39188ZX", "G41247ZX" ], "uniprot_id": "Q7Z7D3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans on glycoproteins, modulating immune checkpoints.", "mechanism": "Galectin-3 binds LAG-3 and modulates immune suppression; inhibitors (GB1211) enhance ICI efficacy.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335673" }, { "confidence": "high", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD68 is a heavily glycosylated lysosomal glycoprotein; glycosylation affects its stability and cell surface expression.", "mechanism": "CD68+ histiocyte proliferation is a hallmark of HNL necrotic lesions.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "high", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD3 is N-glycosylated; glycosylation modulates T-cell receptor signaling.", "mechanism": "CD3+ T-cell infiltration is prominent in HNL, reflecting immune activation.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "medium", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD4 is N-glycosylated; glycosylation regulates receptor stability and ligand binding.", "mechanism": "CD4+ helper T cells are present in HNL lesions, indicating immune response.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "high", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD8 is N-glycosylated; glycosylation influences T-cell cytotoxic function.", "mechanism": "CD8+ cytotoxic T cells densely infiltrate necrotic areas in HNL.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "medium", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD123 is N-glycosylated; glycosylation affects receptor trafficking and immune signaling.", "mechanism": "CD123+ plasmacytoid dendritic cells are scattered in HNL lesions.", "protein": "CD123", "relationship_type": "biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "high", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD20 is glycosylated; glycosylation modulates B-cell receptor function.", "mechanism": "CD20 is absent or weak in HNL, distinguishing it from B-cell lymphomas.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker (negative)", "source_pmcid": "PMC12335763" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "Same as above.", "mechanism": "CD68+ histiocyte pattern differs in lymphoma vs. HNL; less necrosis and more atypia in lymphoma.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "Same as above.", "mechanism": "Polyclonal CD3+ T-cell proliferation in HNL vs. clonal expansion in lymphoma.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC12335763" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Same as above.", "mechanism": "CD68+ histiocytes present in HNL; SLE shows hematoxylin bodies and different histology.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker (differential)", "source_pmcid": "PMC12335763" }, { "confidence": "low", "disease": "Histiocytic necrotizing lymphadenitis (HNL)", "glycan_involvement": "CD30 is glycosylated; glycosylation affects receptor signaling.", "mechanism": "Scattered CD30+ cells indicate immune activation in some HNL cases.", "protein": "CD30", "relationship_type": "biomarker (activation)", "source_pmcid": "PMC12335763" }, { "confidence": "high", "disease": "Hepatitis D", "glycan_involvement": "HBsAg is a glycoprotein; its glycosylation is essential for HDV virion formation and infectivity.", "mechanism": "HDV requires HBsAg glycoprotein for viral assembly, replication, and transmission.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12335798" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation of HBsAg affects immune recognition and persistence, contributing to chronic liver injury.", "mechanism": "HBsAg presence enables HBV and HDV infection, leading to chronic inflammation and fibrosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12335798" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation modulates HBsAg secretion and immune evasion, promoting chronicity.", "mechanism": "Chronic infection with HBV (and HDV) via HBsAg leads to progressive liver damage and cirrhosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12335798" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation of HBsAg may affect oncogenic signaling and immune escape.", "mechanism": "Chronic HBV/HDV infection increases risk of hepatocellular carcinoma via persistent inflammation and fibrosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12335798" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation is required for proper folding and secretion of HBsAg.", "mechanism": "HBsAg is used as a diagnostic marker for HBV infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12335798" }, { "confidence": "high", "disease": "Migraine", "glycan_involvement": "CGRP is a glycoprotein; glycosylation may affect its stability and receptor interaction.", "mechanism": "CGRP is released during migraine attacks, causing vasodilation, neurogenic inflammation, and pain sensitization.", "protein": "CGRP", "relationship_type": "causal", "source_pmcid": "PMC12335800" }, { "confidence": "high", "disease": "Migraine", "glycan_involvement": "Receptor glycosylation may modulate ligand binding and receptor trafficking.", "mechanism": "CGRP receptor antagonists (e.g., Atogepant) block CGRP binding, interrupting migraine cascade.", "protein": "CGRP receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335800" }, { "confidence": "medium", "disease": "Migraine", "glycan_involvement": "PACAP is glycosylated; glycosylation may influence secretion and receptor interaction.", "mechanism": "PACAP is released in the trigeminovascular system, contributing to neurogenic inflammation and migraine.", "protein": "PACAP", "relationship_type": "causal", "source_pmcid": "PMC12335800" }, { "confidence": "medium", "disease": "Chronic migraine", "glycan_involvement": "Glycosylation may affect CGRP half-life and bioactivity.", "mechanism": "Sustained elevation of CGRP contributes to chronic migraine pathophysiology.", "protein": "CGRP", "relationship_type": "causal", "source_pmcid": "PMC12335800" }, { "confidence": "medium", "disease": "Chronic migraine", "glycan_involvement": "Glycosylation may affect receptor function and drug binding.", "mechanism": "CGRP receptor antagonists reduce attack frequency in chronic migraine.", "protein": "CGRP receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335800" }, { "confidence": "medium", "disease": "Episodic migraine", "glycan_involvement": "Glycosylation may modulate peptide stability.", "mechanism": "Transient CGRP release triggers episodic migraine attacks.", "protein": "CGRP", "relationship_type": "causal", "source_pmcid": "PMC12335800" }, { "confidence": "low", "disease": "Migraine", "glycan_involvement": "Receptor glycosylation may influence antagonist efficacy.", "mechanism": "Atogepant also inhibits AMY1 receptor, contributing to migraine prevention.", "protein": "AMY1 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335800" }, { "confidence": "low", "disease": "Hepatotoxicity", "glycan_involvement": "Altered glycosylation could affect clearance and toxicity.", "mechanism": "Elevated CGRP or its antagonism may be monitored in context of drug-induced liver injury.", "protein": "CGRP", "relationship_type": "biomarker", "source_pmcid": "PMC12335800" }, { "confidence": "medium", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "LOXL1 interacts with glycoproteins in ECM (e.g., fibulin-5), but direct glycosylation not specified.", "mechanism": "LOXL1 downregulation associated with RCC occurrence; loss may disrupt ECM homeostasis.", "protein": "LOXL1", "relationship_type": "protective", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Bladder cancer (BLCA)", "glycan_involvement": "Indirect via ECM glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 silenced by promoter methylation; re-expression suppresses Ras/ERK signaling and colony formation.", "protein": "LOXL1", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12335831" }, { "confidence": "medium", "disease": "Salivary adenoid cystic carcinoma (SACC)", "glycan_involvement": "ECM remodeling via glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 upregulated due to low CpG methylation; may promote tumor development and progression.", "protein": "LOXL1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Remodels collagen and interacts with ECM glycoproteins; direct glycosylation not specified.", "mechanism": "LOXL1 upregulated by integrin \u03b111 in CAFs; promotes ECM remodeling, tumor growth, and metastasis.", "protein": "LOXL1", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Pleural mesothelioma (PM)", "glycan_involvement": "ECM glycoprotein involvement; direct glycosylation not specified.", "mechanism": "LOXL1 overexpressed in PM tissues; correlates with poor prognosis.", "protein": "LOXL1", "relationship_type": "biomarker", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Brain glioma", "glycan_involvement": "ECM remodeling and glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 upregulation promotes proliferation, inhibits apoptosis via Wnt/\u03b2-catenin and BAG2 stabilization.", "protein": "LOXL1", "relationship_type": "therapeutic_target/biomarker/causal", "source_pmcid": "PMC12335831" }, { "confidence": "medium", "disease": "Prostate cancer (PRAD)", "glycan_involvement": "Collagen crosslinking and ECM glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 expression promotes progression/metastasis; silencing enhances invasion; role depends on microenvironment.", "protein": "LOXL1", "relationship_type": "dual (tumor-promoting and suppressive)", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Gastric cancer (GC)", "glycan_involvement": "ECM remodeling and glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 upregulated; promotes EMT, migration, poor prognosis via WNT/\u03b2-catenin/cyclinD1 pathway.", "protein": "LOXL1", "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Breast cancer (BC)", "glycan_involvement": "Basement membrane glycoprotein involvement; direct glycosylation not specified.", "mechanism": "LOXL1 upregulated in BC tissues; associated with basement membrane remodeling and EMT.", "protein": "LOXL1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12335831" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "ECM glycoprotein interactions; direct glycosylation not specified.", "mechanism": "LOXL1 expression variable; may suppress or promote CRC via MST1/2-YAP pathway and immune modulation.", "protein": "LOXL1", "relationship_type": "biomarker/dual (tumor-promoting and suppressive)", "source_pmcid": "PMC12335831" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation affects PSA stability and detection in serum assays.", "mechanism": "Elevated serum PSA reflects increased production/secretion by malignant prostate epithelial cells.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation modulates fPSA isoform distribution and immunoreactivity.", "mechanism": "Elevated absolute fPSA levels are associated with advanced and aggressive prostate cancer.", "protein": "fPSA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Heavy N-glycosylation is essential for CEA cell surface expression and immunodetection.", "mechanism": "Elevated serum CEA is linked to aggressive and metastatic prostate cancer phenotypes.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "medium", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "N-glycosylation influences PSA release and serum stability.", "mechanism": "Moderately elevated PSA reflects increased glandular mass and secretion in BPH.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "medium", "disease": "Benign prostatic hyperplasia (BPH)", "glycan_involvement": "N-glycosylation affects fPSA isoform ratios used in differential diagnosis.", "mechanism": "fPSA is higher in BPH than healthy controls, but lower than in prostate cancer.", "protein": "fPSA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Aggressive variant prostate cancer (AVPC)", "glycan_involvement": "N-glycosylation is critical for CEA\u2019s cell surface localization and function.", "mechanism": "CEA overexpression identifies AVPC and correlates with poor prognosis.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation enables CEA detection and immune targeting.", "mechanism": "CEA is overexpressed and used for diagnosis and monitoring recurrence.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation is necessary for CEA\u2019s immunogenicity and detection.", "mechanism": "CEA is elevated in lung cancer and used for prognosis.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "medium", "disease": "Urinary bladder cancer", "glycan_involvement": "N-glycosylation supports CEA\u2019s cell surface expression.", "mechanism": "High CEA expression is linked to high-grade and invasive bladder tumors.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Bone metastasis (secondary to prostate cancer)", "glycan_involvement": "N-glycosylation affects PSA\u2019s serum half-life and detection.", "mechanism": "High PSA levels are positively correlated with bone metastasis risk in prostate cancer.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12335835" }, { "confidence": "high", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "SUMOylation (not classical glycosylation) at K62 regulates HNRNPL stability.", "mechanism": "HNRNPL stabilizes Neat1 lncRNA, promoting caspase-1 activation and hepatocyte pyroptosis.", "protein": "HNRNPL", "protein_enriched": { "function": "Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:225704", "gene_name": "HNRNPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14866" }, "relationship_type": "causal", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "Removes SUMO2/3 (ubiquitin-like modifier) from HNRNPL.", "mechanism": "SENP3 deSUMOylates HNRNPL, leading to its degradation and reduced pyroptosis.", "protein": "SENP3", "protein_enriched": { "function": "Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608, PubMed:36050397). Deconjugates SUMO2 ", "gene_name": "SENP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4L4" }, "relationship_type": "protective", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Pyroptosis-associated Hepatocyte Death", "glycan_involvement": "SUMOylation at K62 protects HNRNPL from degradation.", "mechanism": "High HNRNPL increases Neat1, which enhances caspase-1-mediated pyroptosis.", "protein": "HNRNPL", "protein_enriched": { "function": "Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:225704", "gene_name": "HNRNPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14866" }, "relationship_type": "causal", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Pyroptosis-associated Hepatocyte Death", "glycan_involvement": "DeSUMOylation of HNRNPL.", "mechanism": "SENP3 reduces HNRNPL and Neat1, limiting caspase-1 activation and pyroptosis.", "protein": "SENP3", "protein_enriched": { "function": "Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608, PubMed:36050397). Deconjugates SUMO2 ", "gene_name": "SENP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4L4" }, "relationship_type": "protective", "source_pmcid": "PMC12335969" }, { "confidence": "medium", "disease": "Drug-induced Liver Injury (DILI)", "glycan_involvement": "SUMOylation status modulates HNRNPL levels.", "mechanism": "High HNRNPL correlates with increased pyroptosis and serum ALT in DILI patients.", "protein": "HNRNPL", "protein_enriched": { "function": "Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:225704", "gene_name": "HNRNPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14866" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335969" }, { "confidence": "medium", "disease": "Drug-induced Liver Injury (DILI)", "glycan_involvement": "SUMO2/3 deconjugation activity.", "mechanism": "Low SENP3 correlates with high HNRNPL and increased pyroptosis in DILI.", "protein": "SENP3", "protein_enriched": { "function": "Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608, PubMed:36050397). Deconjugates SUMO2 ", "gene_name": "SENP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4L4" }, "relationship_type": "biomarker", "source_pmcid": "PMC12335969" }, { "confidence": "medium", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Membrane GSDMD correlates with pyroptosis severity and serum ALT.", "protein": "GSDMD", "relationship_type": "biomarker", "source_pmcid": "PMC12335969" }, { "confidence": "medium", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "Stabilized by SUMOylated HNRNPL.", "mechanism": "Neat1 lncRNA interacts with caspase-1 to promote pyroptosis.", "protein": "Neat1", "relationship_type": "causal", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "Targeting SUMOylation/deSUMOylation modulates HNRNPL stability.", "mechanism": "HNRNPL knockdown or degradation reduces hepatocyte pyroptosis and liver injury.", "protein": "HNRNPL", "protein_enriched": { "function": "Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:225704", "gene_name": "HNRNPL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14866" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Acute Liver Injury (ALI)", "glycan_involvement": "Promotes HNRNPL deSUMOylation and degradation.", "mechanism": "Enhancing SENP3 activity or SUMOylation inhibition protects against ALI by reducing pyroptosis.", "protein": "SENP3", "protein_enriched": { "function": "Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608, PubMed:36050397). Deconjugates SUMO2 ", "gene_name": "SENP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H4L4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12335969" }, { "confidence": "high", "disease": "Type 2 diabetes in pregnancy", "glycan_involvement": "AMH is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Elevated AMH in cord blood indicates disrupted ovarian development in female offspring exposed to maternal T2D.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Type 2 diabetes in pregnancy", "glycan_involvement": "APN is heavily glycosylated; glycosylation is essential for multimerization and function.", "mechanism": "Lower APN in cord blood reflects increased fetal insulin resistance and altered metabolic profile.", "protein": "Adiponectin (APN)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Type 2 diabetes in pregnancy", "glycan_involvement": "SHBG glycosylation affects its half-life and binding affinity.", "mechanism": "Reduced SHBG in cord blood is associated with increased insulin resistance and altered sex steroid bioavailability.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Type 2 diabetes in pregnancy", "glycan_involvement": "Insulin is glycosylated; glycosylation affects receptor binding and clearance.", "mechanism": "Elevated insulin in cord blood indicates fetal hyperinsulinemia and insulin resistance due to maternal T2D.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "medium", "disease": "Type 2 diabetes in pregnancy", "glycan_involvement": "IGF-1 glycosylation modulates receptor interaction and stability.", "mechanism": "Higher IGF-1 in cord blood reflects increased fetal growth and altered metabolic programming.", "protein": "Insulin-like growth factor 1 (IGF-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "medium", "disease": "Ovarian dysfunction", "glycan_involvement": "Glycosylation regulates AMH secretion and bioactivity.", "mechanism": "Elevated AMH may disrupt normal follicle development, predisposing to ovarian dysfunction in offspring.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "causal", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for APN multimer formation and insulin-sensitizing activity.", "mechanism": "Lower APN reduces insulin sensitivity, increasing risk of metabolic syndrome in offspring.", "protein": "Adiponectin (APN)", "relationship_type": "protective", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "SHBG glycosylation influences its serum levels and function.", "mechanism": "Low SHBG is a marker of insulin resistance and metabolic risk in newborns.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "medium", "disease": "Fetal metabolic disruption", "glycan_involvement": "Glycosylation may affect AMH transport and activity.", "mechanism": "High AMH in cord blood signals altered intrauterine environment and fetal metabolic programming.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Fetal metabolic disruption", "glycan_involvement": "Glycosylation critical for APN function in metabolic regulation.", "mechanism": "Low APN in cord blood is linked to increased adiposity and metabolic risk in offspring.", "protein": "Adiponectin (APN)", "relationship_type": "biomarker", "source_pmcid": "PMC12336012" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "CA19-9 is a sialylated Lewis antigen (glycan epitope) on mucin-type glycoproteins.", "mechanism": "CA19-9 is elevated in serum of pancreatic cancer patients and used for diagnosis and monitoring.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336018" }, { "confidence": "medium", "disease": "Postoperative pancreatic fistula (POPF)", "glycan_involvement": "Glycosylation determines CA19-9 antigenicity and detection.", "mechanism": "Preoperative CA19-9 levels are measured as part of risk assessment for complications.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336018" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "Albumin is N-glycosylated, which may affect its serum half-life and function.", "mechanism": "Serum albumin is used in the prognostic nutritional index (PNI) to assess nutritional status.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336018" }, { "confidence": "medium", "disease": "Clinically relevant postoperative pancreatic fistula (CR-POPF)", "glycan_involvement": "Altered glycosylation may reflect inflammation or nutritional status.", "mechanism": "Higher preoperative albumin is associated with CR-POPF risk in univariate analysis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336018" }, { "confidence": "high", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "CXCL10 is glycosylated, which affects secretion and receptor binding.", "mechanism": "Upregulated in SIM; recruits immune cells, drives inflammation and muscle damage.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336033" }, { "confidence": "high", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "IL6 glycosylation modulates stability and receptor interaction.", "mechanism": "Upregulated in SIM; promotes muscle protein breakdown and systemic inflammation.", "protein": "IL6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336033" }, { "confidence": "high", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "STAT1 is glycosylated, influencing nuclear translocation and activity.", "mechanism": "Upregulated in SIM; mediates cytokine signaling and immune response.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "Glycosylation affects TNF-alpha secretion and receptor binding.", "mechanism": "Promotes muscle protein breakdown and inflammation in SIM.", "protein": "TNF-alpha", "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "C3 glycosylation is essential for activation and immune complex formation.", "mechanism": "Complement activation contributes to muscle cell damage in SIM.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "Glycosylation modulates IFN-gamma stability and signaling.", "mechanism": "Induces CXCL10 and STAT1, amplifying immune response and muscle injury.", "protein": "Interferon gamma", "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "TLR4 glycosylation is required for ligand recognition and signaling.", "mechanism": "LPS activation of TLR4 triggers cytokine storm and muscle catabolism.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Sepsis-induced myopathy (SIM)", "glycan_involvement": "Glycosylation affects receptor trafficking and ligand binding.", "mechanism": "Involved in chemokine signaling and immune cell recruitment.", "protein": "G protein-coupled receptor", "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates IL6 activity and immune response.", "mechanism": "IL6 drives chronic inflammation and joint damage.", "protein": "IL6", "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Glycosylation regulates CXCL10 secretion and function.", "mechanism": "CXCL10 promotes immune cell infiltration and tissue damage.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "causal", "source_pmcid": "PMC12336033" }, { "confidence": "high", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Folr2 is a glycoprotein; glycosylation is essential for its cell surface localization and ligand binding.", "mechanism": "Folr2 hi macrophages colocalize with CD4+ T cells in CHS-healed skin, marking a major macrophage subset involved in local immune memory.", "protein": "Folr2 (Folate receptor beta)", "protein_enriched": { "function": "Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target p", "gene_name": "Lrrc41", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8K1C9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "high", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "CD4 glycosylation affects T cell receptor interactions and stability.", "mechanism": "CD4+ tissue-resident memory T cells mediate long-term local immune memory and recurrence of CHS.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "CD8 glycosylation modulates T cell activation and migration.", "mechanism": "CD8+ T RM cells mediate early antigen responsiveness in CHS but decline over time.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "causal", "source_pmcid": "PMC12336041" }, { "confidence": "high", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation regulates integrin function and cell adhesion.", "mechanism": "CD103+ marks tissue-resident memory T cells persisting in healed skin.", "protein": "CD103 (Integrin alpha E)", "protein_enriched": { "function": "Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:10872825). May be involved in the control of cAMP-mediated neural activity and cAMP met", "gene_name": "Pde7b", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q9QXQ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "high", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation affects CD69 surface expression and signaling.", "mechanism": "CD69+ expression identifies T RM cells involved in local immune memory.", "protein": "CD69", "protein_enriched": { "function": "Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells ", "gene_name": "CD69", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation modulates scavenger receptor activity.", "mechanism": "CD163+ macrophages colocalize with CD4+ T cells in skin, indicating involvement in immune regulation.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "CD206 is a C-type lectin; glycosylation is critical for ligand recognition.", "mechanism": "CD206+ macrophages interact with CD4+ T cells, possibly influencing antigen uptake.", "protein": "CD206 (Mannose receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation affects CD86-mediated T cell activation.", "mechanism": "CD86+ macrophages colocalize with CD4+ T cells, suggesting a role in costimulation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation modulates Fc receptor binding and function.", "mechanism": "CD64+ macrophages are in contact with CD4+ T cells, indicating involvement in immune complex handling.", "protein": "CD64 (Fc\u03b3RI)", "protein_enriched": { "function": "High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses", "gene_name": "Fcgr1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G16125XL" ], "uniprot_id": "P26151" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "medium", "disease": "Contact hypersensitivity (CHS)", "glycan_involvement": "Glycosylation influences CD68 trafficking and phagocytic activity.", "mechanism": "CD68+ macrophages colocalize with CD4+ T cells in skin, marking myeloid cell involvement.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336041" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "O-glycosylation is essential for MUC2 mucin function and barrier properties.", "mechanism": "MUC2 is highly expressed in CRC and marks goblet cell loss and mucosal barrier dysfunction.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation may affect COX2 stability and secretion.", "mechanism": "COX2 is upregulated in CRC, promoting inflammation and tumorigenesis.", "protein": "COX2 (PTGS2)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation is required for Wnt5a secretion and activity.", "mechanism": "Wnt5a is upregulated in CRC, activating Wnt/\u03b2-catenin signaling and promoting tumor progression.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Potential N-glycosylation may affect stability or localization.", "mechanism": "\u03b2-catenin accumulation drives Wnt pathway activation and CRC cell proliferation.", "protein": "\u03b2-catenin (CTNNB1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336053" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "AXIN1 suppresses Wnt/\u03b2-catenin signaling; its upregulation inhibits CRC progression.", "protein": "AXIN1", "protein_enriched": { "function": "Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453, PubM", "gene_name": "AXIN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15169" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "O-glycosylation critical for barrier function; defects promote inflammation.", "mechanism": "MUC2 maintains mucosal barrier; loss or altered glycosylation increases IBD risk and CRC progression.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12336053" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "N-glycosylation may modulate COX2 function.", "mechanism": "COX2 upregulation mediates inflammation in IBD, increasing CRC risk.", "protein": "COX2 (PTGS2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12336053" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "N-glycosylation required for Wnt5a function.", "mechanism": "Wnt5a-driven signaling contributes to inflammation and tissue remodeling in IBD.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "O-glycosylation essential for mucus gel formation.", "mechanism": "MUC2 O-glycosylation maintains mucus barrier; loss leads to colitis and increased CRC risk.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12336053" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Potential N-glycosylation may modulate function.", "mechanism": "\u03b2-catenin is a hub gene in CRC, targeted by berberine to inhibit tumor growth.", "protein": "\u03b2-catenin (CTNNB1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336053" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "E-cadherin is a glycoprotein; altered glycosylation may further affect adhesion.", "mechanism": "Hypermethylation of CDH1 promoter reduces E-cadherin expression, impairing cell-cell adhesion and promoting ectopic endometrial tissue implantation.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "T-cadherin is a glycoprotein; glycosylation may modulate function.", "mechanism": "Reduced expression correlates with disease severity and impaired cell adhesion.", "protein": "T-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH13", "glycan_count": 81, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI", "G06356OH", "G82463GQ", "G70232NH", "G77669RF", "G04657PL", "G05962QB", "G12341GU", "G27058EU", "G37509XX", "G45395BF", "G53075ES", "G57776ZS", "G80075MS", "G03644CB", "G06247RL", "G08918WF", "G11115RO", "G30221QT", "G50856PC", "G59324HL", "G65414LI", "G81637OR", "G90382BL", "G94665LC", "G00912UN", "G06906LK", "G11314AS", "G14972EH", "G18647XP", "G27126ED", "G29299MO", "G37399XV", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47748JZ", "G47950XN", "G59626AS", "G59924QI", "G63041LO", "G70619PT", "G83646BJ", "G85269DF", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G93656SY", "G96091TT", "G98611JV", "G49108TO", "G01650EU", "G07755XJ", "G17208MA", "G23505EP", "G31852PQ", "G35253PZ", "G43223CG", "G61256FT", "G76295SF", "G85554PZ", "G92551JA", "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G58087IP", "G72747WU", "G82830MN", "G25418HZ", "G31665QC", "G37818NZ", "G37881RL", "G57888GL", "G63040RU", "G80920RR", "G99679NM" ], "uniprot_id": "P55290" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "PR-B is glycosylated; altered glycosylation may affect receptor stability.", "mechanism": "Hypermethylation of PR-B promoter in ectopic endometrium suppresses expression, contributing to progesterone resistance.", "protein": "Progesterone Receptor B (PR-B)", "protein_enriched": { "function": "Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of co", "gene_name": "PGR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06401-2" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "ER-\u03b2 is glycosylated; glycosylation may affect receptor signaling.", "mechanism": "Hypomethylation of ESR2 promoter increases ER-\u03b2 expression, promoting estrogen-driven lesion growth.", "protein": "Estrogen Receptor 2 (ER-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "COX-2 is glycosylated; glycosylation may regulate enzyme activity.", "mechanism": "Promoter hypomethylation increases COX-2 expression, elevating PGE2 and inflammation.", "protein": "Cyclo-oxygenase 2 (COX-2)", "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "medium", "disease": "Infertility", "glycan_involvement": "Loss of glycosylated E-cadherin disrupts adhesion.", "mechanism": "Reduced E-cadherin impairs endometrial receptivity and embryo implantation.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Promoter hypermethylation reduces HOXA10 expression, impairing endometrial differentiation.", "protein": "Homeobox A10 (HOXA10)", "protein_enriched": { "function": "Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to the DNA seque", "gene_name": "HOXA10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P31260" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Hypomethylation of NR5A1 promoter increases SF-1, upregulating steroidogenic enzymes and local estrogen production.", "protein": "Steroidogenic Factor 1 (SF-1)", "protein_enriched": { "function": "Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues (PubMed:27378692). Binds to the Ad4 site found in the promoter region of steroidogeni", "gene_name": "NR5A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13285" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Hypomethylation leads to GATA6 overexpression, promoting estrogen-producing phenotype in stromal cells.", "protein": "GATA6", "protein_enriched": { "function": "Transcriptional activator (PubMed:19666519, PubMed:22750565, PubMed:22824924, PubMed:27756709). Regulates SEMA3C and PLXNA2 (PubMed:19666519). Involved in gene regulation specifically in the gastric e", "gene_name": "GATA6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92908" }, "relationship_type": "causal", "source_pmcid": "PMC12336057" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Altered DNMT1 expression in endometriotic tissue reflects global methylation changes.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336057" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation affects axonal adhesion.", "mechanism": "Altered expression and glycosylation in NAWM; involved in myelin stability and axo-glial interactions.", "protein": "MAG", "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is N-glycosylated; glycan moieties may influence immunogenicity.", "mechanism": "Upregulated in NAWM; target of autoimmune response and demyelination.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC12336099" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Caspr1 is N-glycosylated; glycosylation modulates membrane localization.", "mechanism": "Disrupted paranodal localization in NAWM; affects axo-glial junctions and conduction.", "protein": "Caspr1", "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Contactin 1 is heavily glycosylated; glycosylation critical for function.", "mechanism": "Altered distribution in NAWM; involved in axo-glial adhesion.", "protein": "Contactin 1", "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Chondroitin sulfate glycosylation blocks cell migration/differentiation.", "mechanism": "Aggregates in NAWM; inhibits OPC differentiation and remyelination.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Chondroitin sulfate glycosylation inhibits OPCs.", "mechanism": "Aggregates in NAWM; impairs remyelination.", "protein": "Versican", "protein_enriched": { "function": "May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid", "gene_name": "VCAN", "glycan_count": 91, "glycosylation_sites_count": 34, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G04657PL", "G10488MI", "G20706XG", "G23505EP", "G27058EU", "G40834TG", "G41071NU", "G45395BF", "G46691LC", "G49589RB", "G57776ZS", "G59324HL", "G60834IK", "G63980BQ", "G70232NH", "G73968GN", "G77669RF", "G80075MS", "G80920RR", "G84452RH", "G86880BF", "G90382BL", "G90659AW", "G57317CE", "G13144LI", "G62461SM", "G62765YT", "G73004SD", "G88713AC", "G07246CJ", "G16125XL", "G27915IV", "G31852PQ", "G33791AF", "G41247ZX", "G57888GL", "G68490OW", "G70441OD", "G79666IR", "G80479JV", "G87123QX", "G93718GY", "G11101UV", "G27391WQ", "G32788FZ", "G40926MX", "G69521XL", "G95046LV", "G81006GJ", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G07755XJ", "G08290VR", "G10486CT", "G10819WX", "G11314AS", "G14972EH", "G17208MA", "G23863VK", "G27126ED", "G27947YN", "G34029GR", "G34989PA", "G42124LM", "G43089EG", "G43223CG", "G43669FQ", "G46524LG", "G47644PP", "G51640FO", "G59626AS", "G63041LO", "G64394MX", "G70619PT", "G76295SF", "G80223IX", "G87661QW", "G92050GC", "G92406TI", "G75983OB", "G37881RL", "G22310AV", "G37399XV" ], "uniprot_id": "P13611" }, "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Chondroitin sulfate glycosylation modulates ECM structure.", "mechanism": "Reduced in NAWM; loss may contribute to ECM dysregulation.", "protein": "Neurocan", "relationship_type": "protective", "source_pmcid": "PMC12336099" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MHC class II glycoprotein; glycosylation required for antigen presentation.", "mechanism": "Upregulated in NAGM; associated with increased microglial activation and neuronal damage.", "protein": "HLA-DRB1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12336099" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding.", "mechanism": "Upregulated in NAWM; mediates hyaluronan signaling and ECM remodeling.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12336099" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "N-glycosylation influences channel trafficking and function.", "mechanism": "Altered expression in NAGM; affects astrocyte-oligodendrocyte coupling and neuroinflammation.", "protein": "Connexin 43 (Cx43)", "protein_enriched": { "function": "Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low", "gene_name": "GJA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17302" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336099" }, { "confidence": "high", "disease": "Capsular Warning Syndrome (CWS)", "glycan_involvement": "Glycosylation of GP IIb/IIIa affects receptor function and ligand binding.", "mechanism": "Tirofiban, a GP IIb/IIIa antagonist, inhibits platelet aggregation and reduces infarction risk and improves outcomes in CWS.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336126" }, { "confidence": "high", "disease": "Acute Cerebral Infarction", "glycan_involvement": "Glycosylation modulates receptor conformation and platelet activation.", "mechanism": "Platelet aggregation via GP IIb/IIIa contributes to thrombus formation leading to infarction.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Capsular Warning Syndrome (CWS)", "glycan_involvement": "N-glycosylation of fibrinogen is essential for its interaction with GP IIb/IIIa.", "mechanism": "Fibrinogen binds to GP IIb/IIIa, facilitating platelet aggregation and microthrombus formation in CWS.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Intracranial Atherosclerosis", "glycan_involvement": "Glycosylation influences receptor clustering and platelet-endothelium interactions.", "mechanism": "Platelet activation via GP IIb/IIIa promotes microembolism and branch occlusion in atherosclerotic vessels.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Acute Cerebral Infarction", "glycan_involvement": "Glycosylation state may affect receptor density and function.", "mechanism": "Elevated platelet count and increased GP IIb/IIIa activity predict infarction risk.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC12336126" }, { "confidence": "high", "disease": "Capsular Warning Syndrome (CWS)", "glycan_involvement": "Glycosylation may influence drug binding and efficacy.", "mechanism": "Pharmacological inhibition (tirofiban) of GP IIb/IIIa reduces platelet aggregation and improves functional outcome.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "protective", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Acute Cerebral Infarction", "glycan_involvement": "N-glycosylation required for proper fibrinogen structure and function.", "mechanism": "Fibrinogen cross-linking via GP IIb/IIIa accelerates thrombus formation in infarction.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Capsular Warning Syndrome (CWS)", "glycan_involvement": "Glycosylation modulates receptor activation threshold.", "mechanism": "Platelet hyperreactivity (increased GP IIb/IIIa activity) signals imminent infarction in CWS.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "biomarker", "source_pmcid": "PMC12336126" }, { "confidence": "medium", "disease": "Intracranial Atherosclerosis", "glycan_involvement": "Glycosylation may affect antagonist binding.", "mechanism": "GP IIb/IIIa antagonism (tirofiban) may prevent microembolism in atherosclerotic CWS.", "protein": "Glycoprotein IIb/IIIa (Integrin \u03b1IIb\u03b23)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336126" }, { "confidence": "low", "disease": "Intracranial Atherosclerosis", "glycan_involvement": "N-glycosylation impacts fibrinogen's interaction with platelets.", "mechanism": "Fibrinogen-mediated platelet aggregation contributes to microvascular occlusion in atherosclerosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12336126" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation regulates ICAM-1 cell surface localization and function.", "mechanism": "Butyrate inhibits ICAM-1 expression, reducing monocyte adhesion and arterial inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336178" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation essential for E-selectin ligand binding.", "mechanism": "Butyrate suppresses E-selectin expression, limiting leukocyte recruitment to endothelium.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336178" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ABCA1 trafficking and stability.", "mechanism": "Butyrate upregulates ABCA1 via Sp1, promoting cholesterol efflux and inhibiting foam cell formation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation required for GLUT4 membrane localization.", "mechanism": "Butyrate enhances GLUT4 activity in adipose tissue, improving glucose uptake and insulin sensitivity.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "O-glycosylation modulates GLP-1 stability and activity.", "mechanism": "Butyrate increases GLP-1 secretion, promoting insulin release and glucose homeostasis.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects NPC1L1 function and cholesterol transport.", "mechanism": "Butyrate inhibits NPC1L1, reducing intestinal cholesterol absorption and foam cell formation.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation influences eNOS activity and localization.", "mechanism": "Butyrate (via HDAC inhibition) induces eNOS expression, improving endothelial function and lowering blood pressure.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation required for MCT1 membrane trafficking.", "mechanism": "Impaired MCT1 function reduces butyrate absorption, correlating with elevated blood pressure.", "protein": "MCT1", "relationship_type": "causal", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "O-glycosylation modulates PYY secretion and activity.", "mechanism": "Butyrate stimulates PYY secretion, reducing appetite and promoting weight loss.", "protein": "PYY", "relationship_type": "protective", "source_pmcid": "PMC12336178" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "O-glycosylation affects GIP stability and receptor interaction.", "mechanism": "Butyrate increases GIP secretion, enhancing insulin release and glucose regulation.", "protein": "GIP", "relationship_type": "protective", "source_pmcid": "PMC12336178" }, { "confidence": "high", "disease": "Oral pain", "glycan_involvement": "CRP glycosylation modulates its stability and inflammatory activity.", "mechanism": "CRP levels increase in response to pro-inflammatory diets, correlating with oral pain severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "high", "disease": "Oral pain", "glycan_involvement": "IL-6 glycosylation affects secretion and receptor binding.", "mechanism": "IL-6 is released during inflammasome activation, promoting pain pathways in oral tissues.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "high", "disease": "Oral pain", "glycan_involvement": "TNF-\u03b1 glycosylation influences its bioactivity and receptor interaction.", "mechanism": "TNF-\u03b1 is upregulated by pro-inflammatory diets, exacerbating oral pain via leukocyte infiltration.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "medium", "disease": "Oral pain", "glycan_involvement": "Glycosylation modulates IL-1\u03b2 stability and activity.", "mechanism": "IL-1\u03b2 is part of the inflammatory cascade linked to oral pain.", "protein": "Interleukin-1 beta", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Glycosylation affects IL-6's inflammatory signaling.", "mechanism": "Elevated IL-6 promotes periodontal inflammation and tissue destruction.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12336255" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "CRP glycosylation modulates its inflammatory response.", "mechanism": "CRP is elevated in periodontitis, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "medium", "disease": "Oral cancer", "glycan_involvement": "Glycosylation impacts IL-6's tumor-promoting effects.", "mechanism": "High DII diets increase IL-6, which is associated with oral cancer risk.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "medium", "disease": "Metabolic disease", "glycan_involvement": "Glycosylation affects CRP's half-life and function.", "mechanism": "CRP is a marker of systemic inflammation linked to metabolic disease risk.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "medium", "disease": "Kidney disease", "glycan_involvement": "Glycosylation modulates IL-6's renal effects.", "mechanism": "IL-6 is elevated in kidney disease, reflecting inflammatory status.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12336255" }, { "confidence": "medium", "disease": "Joint pain", "glycan_involvement": "Glycosylation regulates TNF-\u03b1's inflammatory potency.", "mechanism": "TNF-\u03b1 mediates joint inflammation and pain.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12336255" }, { "confidence": "high", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and stability.", "mechanism": "IL-6 drives systemic inflammation and hepatic injury in SD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12336258" }, { "confidence": "high", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Glycosylation modulates IL-1 receptor binding.", "mechanism": "IL-1 mediates autoinflammatory responses and organ damage.", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC12336258" }, { "confidence": "medium", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Glycosylation affects IL-18 secretion.", "mechanism": "IL-18 contributes to cytokine storm and MAS.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12336258" }, { "confidence": "medium", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Glycosylation influences TNF-\u03b1 receptor interaction.", "mechanism": "TNF-\u03b1 promotes systemic inflammation and liver injury.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12336258" }, { "confidence": "high", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Ferritin glycosylation affects serum stability.", "mechanism": "Hyperferritinemia reflects disease activity and MAS risk.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336258" }, { "confidence": "high", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "CRP glycosylation modulates immune recognition.", "mechanism": "CRP elevation indicates acute-phase inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336258" }, { "confidence": "medium", "disease": "Severe liver injury/hepatic dysfunction", "glycan_involvement": "Glycosylation required for \u03b3-GGT enzymatic activity.", "mechanism": "Elevated \u03b3-GGT signals cholestatic liver injury in SD.", "protein": "Gamma-glutamyl transpeptidase (\u03b3-GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12336258" }, { "confidence": "medium", "disease": "Severe liver injury/hepatic dysfunction", "glycan_involvement": "N-glycosylation essential for ALP stability.", "mechanism": "ALP elevation marks hepatic and biliary involvement.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336258" }, { "confidence": "high", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Glycosylation may affect JAK localization and function.", "mechanism": "JAK inhibition (baricitinib) blocks cytokine signaling, reducing inflammation.", "protein": "Janus kinase (JAK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336258" }, { "confidence": "medium", "disease": "Still\u2019s disease (SD)", "glycan_involvement": "Potential glycosylation modulates STAT activity.", "mechanism": "STAT pathway inhibition reduces cytokine-driven pathology.", "protein": "Signal transducer and activator of transcription (STAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336258" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation of CD45 regulates its exclusion from the IS, affecting TCR signaling.", "mechanism": "BTN3A1 inhibits N-glycosylation of CD45, retaining CD45 at the IS and suppressing T cell activation against tumors.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Inhibits N-glycosylation of CD45.", "mechanism": "BTN3A1 suppresses \u03b1\u03b2T cell activation by interfering with CD45 N-glycosylation, promoting tumor immune evasion.", "protein": "BTN3A1", "relationship_type": "causal", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS; glycosylation status not specified.", "mechanism": "HHLA2 binds KIR3DL3 at IS, suppressing NF-\u03baB signaling and inhibiting CD8+ T cell and NK cell cytotoxicity, associated with poor prognosis.", "protein": "HHLA2", "protein_enriched": { "function": "Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade", "gene_name": "HHLA2", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM44" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS.", "mechanism": "KIR3DL3 recruited to IS by HHLA2, inhibits activation signaling, contributing to tumor immune evasion.", "protein": "KIR3DL3", "protein_enriched": { "function": "May regulate nociceptor function and/or development, including the sensation or modulation of pain. Functions as a specific membrane receptor for beta-alanine. Beta-alanine at micromolar doses specifi", "gene_name": "MRGPRD", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q8TDS7" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS.", "mechanism": "CD155 binds KIR2DL5, suppressing NK cell activation and tumor cell killing.", "protein": "CD155", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS.", "mechanism": "KIR2DL5 engagement by CD155 suppresses Vav1/ERK1/2/p90RSK/NF-\u03baB signaling, inhibiting NK cell cytotoxicity.", "protein": "KIR2DL5", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS; glycosylation status not specified.", "mechanism": "CD47 binds SIRP\u03b1, inhibits macrophage phagocytosis of 'self' cells including cancer cells; blockade enhances phagocytosis.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycoprotein interaction at IS.", "mechanism": "SIRP\u03b1 engagement by CD47 inhibits phagocytic synapse formation and myosin IIA assembly, suppressing phagocytosis.", "protein": "SIRP\u03b1", "protein_enriched": { "function": "Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhe", "gene_name": "SIRPA", "glycan_count": 49, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G25451PN", "G45395BF", "G57776ZS", "G79666IR", "G82501QM", "G84452RH", "G87123QX", "G93718GY", "G96577RX", "G06356OH", "G10486CT", "G20210JR", "G23294PN", "G27058EU", "G40926MX", "G59626AS", "G65184UU", "G75983OB", "G80223IX", "G80920RR", "G82463GQ", "G83646BJ", "G49108TO", "G01650EU", "G02815KT", "G02886BB", "G05724UK", "G11314AS", "G18647XP", "G28541PG", "G31852PQ", "G37399XV", "G37995HC", "G39188ZX", "G39446WN", "G41071NU", "G41247ZX", "G49018RC", "G57776ZU", "G59924QI", "G72747WU", "G92406TI", "G95865ZB", "G00406II", "G00912UN", "G09831WQ", "G35541EV", "G82364UA" ], "uniprot_id": "P78324" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "GPI-anchored glycoprotein; glycosylation facilitates membrane localization and immune recognition.", "mechanism": "Ecto-CRT on tumor cells is recognized by NKp46, triggering NK cell cytotoxicity; GPI-anchored CRT enhances killing.", "protein": "CRT (Calreticulin)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336355" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "N-glycosylation determines molecular size and synapse exclusion.", "mechanism": "Axial molecular size and glycosylation of CD45 regulate its exclusion from phagocytic synapses, affecting immune cell signaling and leukemia cell spread.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12336355" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "No direct glycosylation involvement for P53.", "mechanism": "P53 mutations drive tumorigenesis, progression, and invasiveness in HCC.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "causal", "source_pmcid": "PMC12336383" }, { "confidence": "high", "disease": "Poorly differentiated HCC", "glycan_involvement": "No direct glycosylation involvement for P53.", "mechanism": "P53 mutation status correlates with poor histological differentiation and aggressive tumor behavior.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336383" }, { "confidence": "high", "disease": "Undifferentiated HCC", "glycan_involvement": "No direct glycosylation involvement for P53.", "mechanism": "Higher frequency of P53 mutations in undifferentiated HCC, indicating worse prognosis.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336383" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "No direct glycosylation involvement for P53.", "mechanism": "P53 is a promising drug target for HCC therapy, especially in mutated cases.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336383" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Heparan sulfate glycosylation is essential for GPC3 function and cell signaling.", "mechanism": "Glypican-3 expression is associated with HCC and can be predicted by imaging biomarker R2*.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336383" }, { "confidence": "medium", "disease": "Poorly differentiated HCC", "glycan_involvement": "Heparan sulfate glycosylation modulates tumor cell interactions.", "mechanism": "GPC3 is often upregulated in poorly differentiated HCC, marking aggressive disease.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336383" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects antibody recognition and therapeutic efficacy.", "mechanism": "GPC3 is a target for immunotherapy and diagnostic imaging in HCC.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336383" }, { "confidence": "high", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "MSLN is a GPI-anchored glycoprotein; glycosylation is required for cell surface localization and detection.", "mechanism": "MSLN is highly and specifically expressed on EOC cells and can be detected on circulating tumor cells (CTCs) in blood, distinguishing malignant from benign ovarian lesions.", "protein": "Mesothelin (MSLN)", "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "medium", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "MSLN is a target for CAR-T cell therapy and antibody-based therapies due to its tumor-specific expression.", "protein": "Mesothelin (MSLN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336444" }, { "confidence": "medium", "disease": "Mesothelioma", "glycan_involvement": "Glycosylation supports cell surface expression.", "mechanism": "MSLN is overexpressed in mesothelioma, serving as a diagnostic marker and therapeutic target.", "protein": "Mesothelin (MSLN)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336444" }, { "confidence": "medium", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "Glycosylation supports cell surface expression.", "mechanism": "MSLN is overexpressed in pancreatic adenocarcinoma, aiding in diagnosis.", "protein": "Mesothelin (MSLN)", "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "Glycosylation supports cell surface expression.", "mechanism": "MSLN is overexpressed in some non-small cell lung cancers.", "protein": "Mesothelin (MSLN)", "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "high", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "EpCAM is a glycoprotein; glycosylation is important for antibody recognition.", "mechanism": "EpCAM is used for immunomagnetic enrichment of CTCs in EOC diagnosis.", "protein": "EpCAM (CD326)", "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "high", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "Heavily O-glycosylated; glycosylation is essential for antigenicity and detection.", "mechanism": "CA125 is a standard serum biomarker for EOC but has limited specificity and sensitivity.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "high", "disease": "Epithelial ovarian cancer (EOC)", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "HE4 is a serum biomarker for EOC, used especially in combination with CA125.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336444" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation affects antigenicity and cross-reactivity.", "mechanism": "CA125 can be elevated in benign gynecological conditions, reducing specificity for EOC.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12336444" }, { "confidence": "medium", "disease": "Adenomyosis", "glycan_involvement": "Glycosylation affects secretion and detection.", "mechanism": "HE4 can be elevated in adenomyosis, affecting specificity for EOC diagnosis.", "protein": "HE4 (WFDC2)", "protein_enriched": { "function": "Broad range protease inhibitor", "gene_name": "WFDC2", "glycan_count": 89, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22625SJ", "G00912UN", "G02815KT", "G04657PL", "G06110VR", "G06330RB", "G07799LX", "G08110WX", "G08290VR", "G08918WF", "G11314AS", "G11629QQ", "G12793SR", "G14972EH", "G15169WU", "G22572EH", "G23719VF", "G25418HZ", "G26271XI", "G26915XM", "G27058EU", "G27126ED", "G28681TP", "G29299MO", "G31852PQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37412TK", "G39188ZX", "G39643OJ", "G39689FZ", "G40834TG", "G41126SR", "G41247ZX", "G43669FQ", "G45395BF", "G46665ZP", "G47644PP", "G47950XN", "G50282JC", "G51413EV", "G54740VA", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59324HL", "G61806WR", "G62461SM", "G62765YT", "G64275UO", "G64409MC", "G64527OM", "G65000LJ", "G66760KM", "G67900CJ", "G70232NH", "G72667IM", "G72791KH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G79666IR", "G80075MS", "G81198YO", "G82443XX", "G84452RH", "G84862VB", "G85144OK", "G85269DF", "G86880BF", "G88374WZ", "G90382BL", "G90734RJ", "G91473PK", "G92050GC", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95046LV", "G95389BC", "G95678HJ", "G95865ZB", "G96577RX", "G99966GV" ], "uniprot_id": "Q14508" }, "relationship_type": "biomarker (false positive)", "source_pmcid": "PMC12336444" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "AFP is a glycoprotein; its glycosylation affects stability and detection.", "mechanism": "AFP is elevated in HCC and used for diagnosis, prognosis, and monitoring response to therapy.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336487" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation patterns may differ between cirrhosis and HCC.", "mechanism": "AFP may be mildly elevated in cirrhosis, but high levels are more specific for HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336487" }, { "confidence": "medium", "disease": "Portal vein tumor thrombus", "glycan_involvement": "Glycosylation may affect AFP's interaction with other molecules.", "mechanism": "High AFP levels are associated with vascular invasion and poor prognosis in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336487" }, { "confidence": "low", "disease": "Tumor lysis syndrome", "glycan_involvement": "No direct evidence in this article.", "mechanism": "AFP levels may fluctuate with rapid tumor cell death.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336487" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Serum CRP levels reflect systemic inflammation and disease activity in IBD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Ankylosing spondylitis", "glycan_involvement": "Glycosylation modulates CRP's inflammatory properties.", "mechanism": "CRP is used in ASDAS-CRP score to assess disease activity in AS.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "Calprotectin is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "Fecal calprotectin levels indicate intestinal inflammation in IBD.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Crohn's disease", "glycan_involvement": "Glycosylation may influence calprotectin's detection and function.", "mechanism": "Elevated fecal calprotectin is associated with active CD.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation may affect calprotectin's immunogenicity.", "mechanism": "Fecal calprotectin correlates with UC severity.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "pANCA targets glycosylated proteins in neutrophil granules.", "mechanism": "pANCA is frequently positive in UC and used for differential diagnosis.", "protein": "Perinuclear antineutrophil cytoplasmic antibody (pANCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "medium", "disease": "Crohn's disease", "glycan_involvement": "ASCA targets glycan epitopes on yeast cell wall glycoproteins.", "mechanism": "ASCA is often positive in CD and aids in diagnosis.", "protein": "Anti-Saccharomyces cerevisiae antibody (ASCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Ankylosing spondylitis", "glycan_involvement": "HLA-B27 is N-glycosylated; glycosylation affects antigen presentation and immune recognition.", "mechanism": "HLA-B27 is a major genetic risk factor for AS.", "protein": "Human leukocyte antigen B27 (HLA-B27)", "relationship_type": "causal", "source_pmcid": "PMC12336510" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "N-glycosylation modulates HLA-B27's immune interactions.", "mechanism": "HLA-B27 increases risk of IBD-associated spondyloarthropathy.", "protein": "Human leukocyte antigen B27 (HLA-B27)", "relationship_type": "risk factor", "source_pmcid": "PMC12336510" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Targets glycosylated antigens in neutrophils.", "mechanism": "pANCA helps distinguish UC from CD.", "protein": "Perinuclear antineutrophil cytoplasmic antibody (pANCA)", "relationship_type": "biomarker", "source_pmcid": "PMC12336510" }, { "confidence": "high", "disease": "Cutaneous immune-related adverse events (CirAEs)", "glycan_involvement": "THY1 is a heavily N-glycosylated cell-surface glycoprotein; glycosylation is essential for its cell adhesion and immune signaling functions.", "mechanism": "Upregulated THY1 expression in CirAE lesions suggests involvement in inflammatory response and tissue remodeling.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "medium", "disease": "Spongiotic dermatitis", "glycan_involvement": "Glycosylation of THY1 modulates its interaction with immune cells in inflamed skin.", "mechanism": "THY1 upregulation observed in spongiotic CirAE lesions, indicating a role in acute inflammatory skin reactions.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "medium", "disease": "Lichenoid drug reaction / lichen planus", "glycan_involvement": "THY1 glycosylation may influence T-cell adhesion and migration in lichenoid reactions.", "mechanism": "Elevated THY1 expression in lichenoid CirAE lesions suggests involvement in T-cell mediated skin inflammation.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "low", "disease": "Morbilliform drug reaction", "glycan_involvement": "Glycosylation status may affect THY1-mediated immune cell recruitment.", "mechanism": "THY1 upregulation in morbilliform CirAE lesions indicates a role in drug-induced skin inflammation.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "low", "disease": "Psoriasis-like lesions", "glycan_involvement": "N-glycosylation of THY1 is important for its function in cell-cell interactions in psoriatic inflammation.", "mechanism": "THY1 expression increased in psoriasiform CirAE lesions, possibly reflecting fibroblast and endothelial activation.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "low", "disease": "Interface dermatitis", "glycan_involvement": "Glycosylation may regulate THY1-mediated immune signaling at the dermal-epidermal junction.", "mechanism": "THY1 upregulation in interface dermatitis CirAE lesions suggests involvement in immune cell infiltration.", "protein": "THY1 (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC12336593" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "E-cadherin is a glycoprotein; glycosylation is essential for cell-cell adhesion.", "mechanism": "Loss of E-cadherin function promotes EMT and invasion.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect; Slug regulates glycoprotein E-cadherin.", "mechanism": "Slug represses E-cadherin transcription, promoting EMT and invasion.", "protein": "Slug (SNAI2)", "protein_enriched": { "function": "Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transc", "gene_name": "SNAI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43623" }, "relationship_type": "causal", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect; Snail regulates glycoprotein E-cadherin.", "mechanism": "Snail represses E-cadherin transcription, promoting EMT and invasion.", "protein": "Snail (SNAI1)", "relationship_type": "causal", "source_pmcid": "PMC12336670" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Indirect via E-cadherin repression.", "mechanism": "High Slug expression correlates with poor prognosis.", "protein": "Slug (SNAI2)", "protein_enriched": { "function": "Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transc", "gene_name": "SNAI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43623" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336670" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Indirect via E-cadherin repression.", "mechanism": "High Slug expression correlates with poor prognosis.", "protein": "Slug (SNAI2)", "protein_enriched": { "function": "Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transc", "gene_name": "SNAI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43623" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect via E-cadherin regulation.", "mechanism": "Pdcd4 suppresses Slug translation, maintaining E-cadherin and inhibiting invasion.", "protein": "Pdcd4", "protein_enriched": { "function": "Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the act", "gene_name": "PDCD4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q53EL6" }, "relationship_type": "protective", "source_pmcid": "PMC12336670" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "u-PAR is a membrane glycoprotein; glycosylation required for function.", "mechanism": "u-PAR promotes extracellular matrix degradation and invasion.", "protein": "u-PAR (PLAUR)", "relationship_type": "causal", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "None direct.", "mechanism": "Inhibition of eIF4A (e.g., by silvestrol) reduces Slug translation and invasion.", "protein": "eIF4A", "protein_enriched": { "function": "ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome (PubMed:20156963). In the current model of translation initi", "gene_name": "EIF4A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60842" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect via E-cadherin.", "mechanism": "Slug knockdown restores E-cadherin and suppresses invasion.", "protein": "Slug (SNAI2)", "protein_enriched": { "function": "Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transc", "gene_name": "SNAI2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43623" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Indirect via E-cadherin.", "mechanism": "Low Pdcd4 expression correlates with increased invasion and metastasis.", "protein": "Pdcd4", "protein_enriched": { "function": "Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the act", "gene_name": "PDCD4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q53EL6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12336670" }, { "confidence": "high", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "GPCRs are membrane glycoproteins; glycosylation affects folding, trafficking, and ligand binding.", "mechanism": "Dysregulation of GPCR signaling leads to abnormal cellular responses to extracellular signals.", "protein": "GPCR (G protein-coupled receptor)", "relationship_type": "causal", "source_pmcid": "PMC12336858" }, { "confidence": "medium", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "Glycosylation may regulate G\u03b1 protein stability and interactions.", "mechanism": "Altered G\u03b1 activation impairs downstream signaling, contributing to disease.", "protein": "Heterotrimeric G\u03b1 proteins (Gi, Gq)", "relationship_type": "causal", "source_pmcid": "PMC12336858" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation modulates receptor function and cell surface expression.", "mechanism": "GPCRs mediate cardiovascular responses; dysregulation leads to disease.", "protein": "GPCR (G protein-coupled receptor)", "relationship_type": "causal", "source_pmcid": "PMC12336858" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "Glycosylation influences ligand binding and receptor localization.", "mechanism": "GPCRs respond to neurotransmitters; dysfunction affects neural signaling.", "protein": "GPCR (G protein-coupled receptor)", "relationship_type": "causal", "source_pmcid": "PMC12336858" }, { "confidence": "medium", "disease": "Metabolic disorders", "glycan_involvement": "Glycosylation affects receptor stability and signaling.", "mechanism": "GPCRs regulate hormone and metabolite signaling; dysregulation impacts metabolism.", "protein": "GPCR (G protein-coupled receptor)", "relationship_type": "causal", "source_pmcid": "PMC12336858" }, { "confidence": "low", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "Potential glycosylation may affect GINIP's regulatory function.", "mechanism": "GINIP binds active Gi, modulating GPCR signaling.", "protein": "GINIP", "relationship_type": "regulatory/biomarker", "source_pmcid": "PMC12336858" }, { "confidence": "low", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "Glycosylation may influence GRK2 localization and function.", "mechanism": "GRK2 regulates Gq signaling by binding active Gq.", "protein": "GRK2", "relationship_type": "regulatory/biomarker", "source_pmcid": "PMC12336858" }, { "confidence": "low", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "Glycosylation may modulate Ric-8A stability.", "mechanism": "Ric-8A acts as a chaperone for Gq, affecting GPCR signaling.", "protein": "Ric-8A", "relationship_type": "regulatory", "source_pmcid": "PMC12336858" }, { "confidence": "low", "disease": "Various human diseases (GPCR dysregulation)", "glycan_involvement": "Glycosylation may affect \u03b2-arrestin interactions.", "mechanism": "\u03b2-arrestins mediate alternative GPCR signaling pathways.", "protein": "\u03b2-arrestins", "relationship_type": "regulatory", "source_pmcid": "PMC12336858" }, { "confidence": "medium", "disease": "Severe adenovirus pneumonia (SAP)", "glycan_involvement": "Glycosylation of host cell receptors and viral fiber protein influences binding and tropism.", "mechanism": "Mediates viral attachment and entry into respiratory epithelial cells, initiating infection.", "protein": "Adenovirus fiber protein", "protein_enriched": { "function": "Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chapero", "gene_name": "L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04133" }, "relationship_type": "causal", "source_pmcid": "PMC12336873" }, { "confidence": "medium", "disease": "Severe adenovirus pneumonia (SAP)", "glycan_involvement": "Hexon protein is glycosylated, affecting immune recognition.", "mechanism": "Major capsid protein; triggers immune response and inflammation.", "protein": "Adenovirus hexon protein", "relationship_type": "causal", "source_pmcid": "PMC12336873" }, { "confidence": "medium", "disease": "Severe adenovirus pneumonia (SAP)", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "Used as immunomodulatory therapy to neutralize virus and modulate inflammation.", "protein": "Intravenous immunoglobulin (IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Severe adenovirus pneumonia (SAP)", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "Elevated in cytokine storm; monoclonal antibodies targeting TNF-\u03b1 considered as therapy.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Severe adenovirus pneumonia (SAP)", "glycan_involvement": "Glycosylation modulates IL-6 stability and receptor interaction.", "mechanism": "Key mediator in inflammatory storm; anti-IL-6 therapy proposed.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycan interactions facilitate viral entry into alveolar cells.", "mechanism": "Initiates infection leading to alveolar damage and ARDS.", "protein": "Adenovirus fiber protein", "protein_enriched": { "function": "Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chapero", "gene_name": "L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04133" }, "relationship_type": "causal", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Septic shock", "glycan_involvement": "Glycosylation may modulate immune activation.", "mechanism": "Triggers systemic inflammation contributing to septic shock.", "protein": "Adenovirus hexon protein", "relationship_type": "causal", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Septic shock", "glycan_involvement": "Glycosylation affects TNF-\u03b1 function.", "mechanism": "Major mediator of septic shock; anti-TNF-\u03b1 therapy considered.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Multiple organ dysfunction syndrome (MODS)", "glycan_involvement": "Glycosylation influences IL-6 signaling.", "mechanism": "High IL-6 levels associated with MODS in SAP.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "low", "disease": "Septic shock", "glycan_involvement": "Fc glycosylation critical for anti-inflammatory effects.", "mechanism": "Used to modulate immune response in septic shock.", "protein": "Intravenous immunoglobulin (IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12336873" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation may affect Bcl2 stability and apoptotic signaling.", "mechanism": "Downregulation of Bcl2 promotes apoptosis in A549 lung cancer cells upon FZ-DADA treatment.", "protein": "Bcl2", "protein_enriched": { "function": "Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondria", "gene_name": "BCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10415" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation may modulate BAX localization and function.", "mechanism": "Upregulation of BAX induces apoptosis in A549 cells after FZ-DADA treatment.", "protein": "BAX", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation may regulate caspase-3 activation and substrate recognition.", "mechanism": "Activation of caspase-3 drives apoptosis in lung cancer cells treated with FZ-DADA.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may influence caspase-7 activity.", "mechanism": "Activation of caspase-7 contributes to apoptosis in A549 cells after FZ-DADA treatment.", "protein": "Caspase-7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may affect PARP function and DNA repair.", "mechanism": "PARP cleavage by activated caspases enhances apoptosis in FZ-DADA treated cells.", "protein": "PARP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may regulate Cyclin A stability and cell cycle progression.", "mechanism": "Inhibition of Cyclin A leads to cell cycle arrest in A549 cells after FZ-DADA treatment.", "protein": "Cyclin A", "protein_enriched": { "function": "Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-d", "gene_name": "CCNA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20248" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may modulate Cyclin E degradation and activity.", "mechanism": "Inhibition of Cyclin E induces cell cycle arrest in lung cancer cells treated with FZ-DADA.", "protein": "Cyclin E", "protein_enriched": { "function": "Essential for the control of the cell cycle at the G1/S (start) transition", "gene_name": "CCNE1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24864" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Glycosylation may affect PDK localization and enzymatic activity.", "mechanism": "Inhibition of PDK by DADA disrupts cancer cell metabolism and enhances anti-tumor effect.", "protein": "PDK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337031" }, { "confidence": "low", "disease": "Liver injury", "glycan_involvement": "Glycosylation may influence Bcl2 anti-apoptotic function in hepatocytes.", "mechanism": "DADA provides hepatoprotective effects, potentially via modulation of Bcl2-mediated apoptosis.", "protein": "Bcl2", "protein_enriched": { "function": "Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondria", "gene_name": "BCL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10415" }, "relationship_type": "protective", "source_pmcid": "PMC12337031" }, { "confidence": "low", "disease": "Liver injury", "glycan_involvement": "Glycosylation may regulate PARP-mediated DNA repair in liver cells.", "mechanism": "PARP activity may be involved in liver cell survival during FZ-DADA treatment.", "protein": "PARP", "relationship_type": "protective", "source_pmcid": "PMC12337031" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "None; KRAS is not glycosylated.", "mechanism": "KRAS G12C mutation drives oncogenic signaling, leading to uncontrolled proliferation.", "protein": "KRAS", "relationship_type": "causal", "source_pmcid": "PMC12337048" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "EGFR is N-glycosylated, affecting ligand binding and signaling.", "mechanism": "EGFR activation promotes KRAS signaling; targeted by inhibitors and TCM compounds.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337048" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "PD-L1 glycosylation stabilizes protein and modulates immune recognition.", "mechanism": "KRAS-mutant tumors express higher PD-L1, predicting better response to immune checkpoint inhibitors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12337048" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "ICAM1 is heavily N-glycosylated, influencing cell adhesion and immune interactions.", "mechanism": "KRAS activation upregulates ICAM1, recruiting pro-inflammatory macrophages.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC12337048" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "MET is N-glycosylated, affecting receptor stability and signaling.", "mechanism": "MET amplification contributes to resistance to KRAS G12C inhibitors via activation of MAPK and AKT-mTOR pathways.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337048" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "ITGB4 is N-glycosylated, modulating cell adhesion and signaling.", "mechanism": "ITGB4 overexpression activates AKT-mTOR pathway, mediating resistance to KRAS inhibitors.", "protein": "ITGB4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12337048" }, { "confidence": "medium", "disease": "Squamous cell carcinoma", "glycan_involvement": "PD-L1 glycosylation affects immune evasion.", "mechanism": "PD-L1 expression in transformed squamous cell carcinoma after KRAS inhibitor therapy predicts immunotherapy response.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337048" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "EGFR N-glycosylation modulates drug binding.", "mechanism": "EGFR targeted by cetuximab; TCM compounds enhance efficacy in KRAS-mutant colorectal cancer.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337048" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "None; KEAP1 is not glycosylated.", "mechanism": "KEAP1 co-mutation with KRAS predicts poor prognosis and resistance to KRAS inhibitors.", "protein": "KEAP1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12337048" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "None; STK11 is not glycosylated.", "mechanism": "STK11 co-mutation with KRAS leads to poor response to PD-(L)1 inhibitors and worse survival.", "protein": "STK11", "protein_enriched": { "function": "Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, ", "gene_name": "STK11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15831" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12337048" }, { "confidence": "high", "disease": "Warm autoimmune hemolytic anemia (wAIHA)", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects Fc-mediated effector functions.", "mechanism": "IgG autoantibodies bind to RBC surface glycoproteins, marking them for destruction by macrophages.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Warm autoimmune hemolytic anemia (wAIHA)", "glycan_involvement": "C3 is glycosylated; glycosylation affects complement activation and binding.", "mechanism": "C3 deposition on RBCs detected by DAT can indicate complement-mediated hemolysis.", "protein": "Complement component 3 (C3)", "relationship_type": "biomarker", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Warm autoimmune hemolytic anemia (wAIHA)", "glycan_involvement": "Kidd antigen is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-Jk autoantibodies target RBC glycoproteins (Kidd antigen), leading to hemolysis.", "protein": "Anti-Jk antibodies", "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Warm autoimmune hemolytic anemia (wAIHA)", "glycan_involvement": "BmP53 is a glycoprotein; glycosylation may contribute to mimicry and immune evasion.", "mechanism": "BmP53 molecular mimicry with host platelet glycoproteins may trigger autoimmunity.", "protein": "BmP53", "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Babesiosis", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "IgG autoantibody production may be increased in response to Babesia infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12337370" }, { "confidence": "high", "disease": "Warm autoimmune hemolytic anemia (wAIHA)", "glycan_involvement": "RBC surface glycoproteins are glycosylated; glycosylation affects antibody binding.", "mechanism": "DAT detects IgG and/or C3 bound to RBC surface glycoproteins, confirming wAIHA.", "protein": "Direct antiglobulin test (DAT) target proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12337370" }, { "confidence": "high", "disease": "Hemolysis", "glycan_involvement": "IgG glycosylation influences Fc receptor interactions and clearance.", "mechanism": "IgG-mediated opsonization of RBCs leads to their destruction and hemolysis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Babesiosis", "glycan_involvement": "Glycosylation of BmP53 may enhance mimicry and immune escape.", "mechanism": "BmP53 facilitates Babesia infection and immune evasion via molecular mimicry.", "protein": "BmP53", "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Altered IgG glycosylation is linked to SLE activity.", "mechanism": "IgG autoantibodies are involved in SLE pathogenesis, including hemolytic anemia.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337370" }, { "confidence": "medium", "disease": "Chronic lymphocytic leukemia", "glycan_involvement": "IgG glycosylation patterns may be altered in CLL.", "mechanism": "IgG autoantibodies may be produced in CLL, predisposing to wAIHA.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12337370" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Platelet glycoproteins mediate adhesion/aggregation; glycosylation affects function.", "mechanism": "Platelet count reflects endothelial activation and microthrombi formation in diabetes.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates platelet-endothelium interactions.", "mechanism": "Thrombocytopenia indicates increased platelet consumption due to endothelial activation, predicting cardiovascular risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "high", "disease": "All-cause mortality", "glycan_involvement": "Glycan structures on platelet glycoproteins influence clearance and function.", "mechanism": "Low platelet count in EASIX is associated with increased all-cause mortality.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "LDH is glycosylated, which may affect stability and secretion.", "mechanism": "Elevated LDH reflects endothelial cell death and tissue injury in diabetes.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may modulate LDH activity and clearance.", "mechanism": "High LDH levels indicate increased cellular turnover and hypoxia, predicting cardiovascular events.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "high", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation regulates platelet interaction with endothelium.", "mechanism": "Platelet activation and aggregation contribute to microvascular injury and endothelial dysfunction.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337403" }, { "confidence": "medium", "disease": "Prediabetes", "glycan_involvement": "Glycan changes may precede functional platelet alterations.", "mechanism": "Altered platelet count in EASIX predicts risk of progression and vascular complications in prediabetes.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "medium", "disease": "All-cause mortality", "glycan_involvement": "LDH glycosylation may affect its serum levels.", "mechanism": "Elevated LDH in EASIX is independently associated with increased all-cause mortality.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337403" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Therapeutic modulation of glycosylation could alter platelet function.", "mechanism": "Targeting platelet activation may reduce endothelial injury and complications in diabetes.", "protein": "Platelet glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337403" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycan-targeted therapies could modulate platelet-endothelial interactions.", "mechanism": "Interventions affecting platelet glycoprotein function may lower cardiovascular risk.", "protein": "Platelet glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337403" }, { "confidence": "high", "disease": "Gastrointestinal bleeding (GIB)", "glycan_involvement": "Albumin is N-glycosylated, which affects its stability and half-life; hypoalbuminemia may reflect altered glycosylation in liver dysfunction.", "mechanism": "Low serum albumin reflects impaired hepatic synthetic function, malnutrition, and systemic inflammation, all associated with increased mortality in GIB.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "high", "disease": "Gastrointestinal bleeding (GIB)", "glycan_involvement": "N-glycosylation is essential for secretion and function of prothrombin; liver dysfunction may alter glycosylation.", "mechanism": "Reduced prothrombin activity (reflected by elevated INR) indicates impaired coagulation, increasing bleeding risk and mortality.", "protein": "Prothrombin (Factor II)", "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Gastrointestinal bleeding (GIB)", "glycan_involvement": "N-glycosylation required for secretion and activity; altered in liver disease.", "mechanism": "Decreased Factor VII activity (contributing to elevated INR) impairs clot formation, worsening bleeding outcomes.", "protein": "Coagulation Factor VII", "protein_enriched": { "function": "Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or t", "gene_name": "F7", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G71142DF", "G84224TW", "G82576YO", "G96881BQ", "G06215XQ", "G08146BT", "G23695IQ", "G35061TJ", "G42358LZ", "G50739NP", "G71527NE", "G75494EI", "G91130VE", "G00912UN", "G08918WF", "G40574BA", "G43669FQ", "G45395BF" ], "uniprot_id": "P08709" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Gastrointestinal bleeding (GIB)", "glycan_involvement": "N-glycosylation affects stability and function; may be altered in hepatic dysfunction.", "mechanism": "Reduced Factor IX (part of INR) impairs coagulation, increasing risk of uncontrolled bleeding.", "protein": "Coagulation Factor IX", "protein_enriched": { "function": "Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipid", "gene_name": "F9", "glycan_count": 37, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27608TI", "G50236GJ", "G70593HA", "G76163CP", "G96881BQ", "G10651WD", "G45637XA", "G70649KP", "G81006GJ", "G29068FM", "G43417UB", "G18717LR", "G74722FL", "G57321FI", "G10008NR", "G12743GW", "G12793SR", "G15016TE", "G15169WU", "G17827EU", "G28847IN", "G31639NG", "G32551IQ", "G38277AO", "G39595FH", "G47518TP", "G48414YA", "G52527GH", "G58489ZK", "G66088HZ", "G69834CE", "G74815GQ", "G79318PG", "G86904UH", "G87108ET", "G92975MH", "G98725UL" ], "uniprot_id": "P00740" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Gastrointestinal bleeding (GIB)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Deficiency (reflected in INR) leads to impaired thrombin generation and poor hemostasis.", "protein": "Coagulation Factor X", "protein_enriched": { "function": "Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting (PubMed:22409427). Factor Xa activate", "gene_name": "F10", "glycan_count": 35, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G43417UB", "G53434XO", "G06356OH", "G18938DW", "G20425TQ", "G23863VK", "G24501HF", "G29857RC", "G32854GF", "G36191CD", "G41882MT", "G45359RY", "G46568MX", "G47012YE", "G49478NM", "G50045TK", "G59536GA", "G68866GS", "G72797UR", "G73073LQ", "G75850OP", "G78059CC", "G79809MM", "G81263BG", "G84452RH", "G85678WN", "G87123QX", "G88068QT", "G91365ZQ", "G00912UN", "G11314AS", "G57321FI", "G49108TO", "G80111QD", "G81006GJ" ], "uniprot_id": "P00742" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation patterns in cirrhosis may affect albumin function and clearance.", "mechanism": "Hypoalbuminemia is a marker of advanced liver disease and poor prognosis in cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "N-glycosylation critical for function; altered in liver disease.", "mechanism": "Deficiency due to impaired hepatic synthesis contributes to coagulopathy in cirrhosis.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Acute phase response may alter glycosylation, affecting albumin\u2019s half-life.", "mechanism": "Low albumin reflects systemic inflammation and capillary leak, associated with worse outcomes in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation in cancer may affect albumin function.", "mechanism": "Low albumin is a marker of poor hepatic reserve and prognosis in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "Glycosylation status may modulate albumin\u2019s vascular and hemostatic roles.", "mechanism": "Hypoalbuminemia exacerbates vascular leak and hemostatic imbalance, worsening coagulopathy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337426" }, { "confidence": "high", "disease": "Wound healing impairment", "glycan_involvement": "Glycosylation modulates extracellular matrix interactions and angiogenic signaling.", "mechanism": "Promotes angiogenesis and remodeling, anti-inflammatory and anti-fibrotic effects during wound healing.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337429" }, { "confidence": "high", "disease": "Angiogenesis deficiency", "glycan_involvement": "Glycosylation affects cell adhesion and vessel formation.", "mechanism": "Marker for endothelial cells and neovascularization; increased CD31+ vessels indicate enhanced angiogenesis.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12337429" }, { "confidence": "high", "disease": "Angiogenesis deficiency", "glycan_involvement": "Sialylated glycan chains regulate angiogenic signaling.", "mechanism": "EMCN+CD31+ vessels mark neovascularization and vascular development.", "protein": "EMCN", "protein_enriched": { "function": "Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellul", "gene_name": "EMCN", "glycan_count": 7, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G29068FM", "G53434XO", "G73004SD", "G43417UB", "G57317CE", "G58001LT", "G49108TO" ], "uniprot_id": "Q9ULC0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates secretion and receptor binding.", "mechanism": "Anti-inflammatory cytokine; increased TGF-\u03b2+ cells correlate with reduced inflammation and improved healing.", "protein": "TGF-\u03b2", "relationship_type": "protective", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects cytokine stability and activity.", "mechanism": "Pro-inflammatory cytokine; increased TNF-\u03b1+ cells correlate with impaired healing and inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Fibrosis/scarring", "glycan_involvement": "Glycosylation influences collagen fibril formation.", "mechanism": "Collagen deposition (Col1a1+) marks fibrosis and scarring; reduced Col1a1+ area indicates less scarring.", "protein": "Col1a1", "relationship_type": "biomarker", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Angiogenesis deficiency", "glycan_involvement": "Glycosylation may affect cytoskeletal organization.", "mechanism": "\u03b1-SMA+ vessels indicate vascular maturation and structural completeness.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Wound healing impairment", "glycan_involvement": "Glycosylation may modulate protein-protein interactions in TNT formation.", "mechanism": "Regulates formation of tunneling nanotubes (TNTs) for mitochondrial transfer, enhancing wound healing.", "protein": "TNFAIP2", "protein_enriched": { "function": "May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection", "gene_name": "BAIAP2L1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UHR4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Fibrosis/scarring", "glycan_involvement": "Glycosylation regulates ECM binding and anti-fibrotic activity.", "mechanism": "Anti-fibrotic glycoprotein; inhibits excessive collagen deposition and scarring.", "protein": "IGFBP7", "protein_enriched": { "function": "Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis (PubMed:38218180)", "gene_name": "IGFBP7", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "Q16270" }, "relationship_type": "protective", "source_pmcid": "PMC12337429" }, { "confidence": "medium", "disease": "Skin defects", "glycan_involvement": "Sialylated glycans facilitate endothelial cell function.", "mechanism": "Promotes vascular development and tissue repair in skin defects.", "protein": "EMCN", "protein_enriched": { "function": "Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellul", "gene_name": "EMCN", "glycan_count": 7, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G29068FM", "G53434XO", "G73004SD", "G43417UB", "G57317CE", "G58001LT", "G49108TO" ], "uniprot_id": "Q9ULC0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337429" }, { "confidence": "high", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation modulates its stability and inflammatory activity.", "mechanism": "Elevated fibrinogen levels are associated with increased plaque vulnerability due to pro-thrombotic and inflammatory effects.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "high", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; reflects systemic glycation burden affecting vascular proteins.", "mechanism": "Higher HbA1c reflects chronic hyperglycemia, promoting vascular glycation and plaque instability.", "protein": "Glycosylated Hemoglobin A1c (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "LDL contains N-glycosylated apolipoprotein B-100; glycosylation affects LDL uptake and atherogenicity.", "mechanism": "LDL levels and glycoprotein modifications contribute to plaque lipid core formation and instability.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "HDL contains N-glycosylated apolipoprotein A-I; glycosylation modulates HDL function.", "mechanism": "Higher HDL is protective; glycoprotein structure influences anti-inflammatory and cholesterol efflux functions.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "HDL glycosylation status may affect ratio and vascular effects.", "mechanism": "Elevated UHR indicates oxidative stress and reduced HDL-mediated protection, increasing plaque vulnerability.", "protein": "Uric Acid to HDL Ratio (UHR)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Glucose and lipoprotein glycosylation contribute to metabolic risk.", "mechanism": "High TyG index reflects insulin resistance and metabolic dysfunction, promoting plaque instability.", "protein": "Triglyceride-Glucose Index (TyG)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "HDL glycosylation influences index and anti-atherogenic properties.", "mechanism": "High AIP indicates increased small dense LDL and low HDL, associated with plaque vulnerability.", "protein": "Atherogenic Index of Plasma (AIP)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Surface glycoproteins on immune cells modulate inflammatory signaling.", "mechanism": "Elevated NLR reflects systemic inflammation, contributing to plaque destabilization.", "protein": "Neutrophil-to-Lymphocyte Ratio (NLR)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Immune cell glycoproteins involved in cell-cell interactions and inflammation.", "mechanism": "High SII indicates heightened immune-inflammatory activity, linked to plaque vulnerability.", "protein": "Systemic Immune-Inflammation Index (SII)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "medium", "disease": "Vulnerable Carotid Plaque", "glycan_involvement": "Glycoproteins on immune cells mediate inflammatory responses.", "mechanism": "Elevated SIRI reflects combined neutrophil and monocyte-driven inflammation, increasing plaque risk.", "protein": "Systemic Inflammation Response Index (SIRI)", "relationship_type": "biomarker", "source_pmcid": "PMC12337436" }, { "confidence": "high", "disease": "Stress ulcer", "glycan_involvement": "Glycosylation affects drug stability and delivery.", "mechanism": "Suppresses gastric acid secretion to prevent mucosal injury.", "protein": "Pantoprazole", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337440" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation critical for factor activity.", "mechanism": "Deficiency or dysfunction increases risk of GI bleeding.", "protein": "Coagulation factors", "relationship_type": "causal", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "Gastrointestinal bleeding", "glycan_involvement": "Glycosylation modulates platelet adhesion.", "mechanism": "Platelet dysfunction impairs clot formation in GI tract.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337440" }, { "confidence": "high", "disease": "Stress ulcer", "glycan_involvement": "O-glycosylation essential for mucin gel formation.", "mechanism": "Mucins form a glycoprotein-rich barrier protecting gastric epithelium.", "protein": "Gastric mucins", "relationship_type": "protective", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "Stress ulcer", "glycan_involvement": "Glycosylation affects receptor localization and function.", "mechanism": "Blockade reduces acid secretion, lowering ulcer risk.", "protein": "Histamine-2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "NSAID-induced ulcer", "glycan_involvement": "NSAIDs alter glycosylation of protective proteins.", "mechanism": "NSAIDs disrupt glycoprotein-mediated mucosal protection.", "protein": "NSAID-modified glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "Glucocorticoid-induced ulcer", "glycan_involvement": "Glycosylation regulates receptor signaling.", "mechanism": "High-dose steroids impair mucosal glycoprotein synthesis.", "protein": "Glucocorticoid receptor", "relationship_type": "causal", "source_pmcid": "PMC12337440" }, { "confidence": "low", "disease": "Renal insufficiency", "glycan_involvement": "Altered glycosylation impairs detoxification.", "mechanism": "Accumulation of toxins disrupts glycoprotein function in GI tract.", "protein": "Uremic toxin-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "Polypharmacy-associated GI bleeding", "glycan_involvement": "Glycosylation may affect drug-drug interactions.", "mechanism": "Reduces acid-mediated mucosal injury in patients on multiple drugs.", "protein": "Pantoprazole", "relationship_type": "protective", "source_pmcid": "PMC12337440" }, { "confidence": "medium", "disease": "Drug-induced mucosal injury", "glycan_involvement": "O-glycosylation maintains mucin barrier properties.", "mechanism": "Mucins buffer against chemical injury from drugs.", "protein": "Gastric mucins", "relationship_type": "protective", "source_pmcid": "PMC12337440" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 stability and receptor binding.", "mechanism": "Promotes hepatocyte damage and impairs insulin signaling via proinflammatory activity.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337478" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation affects IL-6 secretion and bioactivity.", "mechanism": "Drives hepatic inflammation and steatosis through immune activation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12337478" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Surface glycoproteins mediate platelet-endothelial interactions.", "mechanism": "Facilitate leukocyte adhesion and amplify intrahepatic inflammation.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337478" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation regulates neutrophil migration and activation.", "mechanism": "Produce ROS and cytokines, contributing to liver injury.", "protein": "Neutrophil glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337478" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation influences monocyte differentiation and signaling.", "mechanism": "Release proinflammatory mediators, aggravating hepatic damage.", "protein": "Monocyte glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12337478" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates lymphocyte trafficking and function.", "mechanism": "Immune surveillance; lymphopenia reflects immune exhaustion.", "protein": "Lymphocyte glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12337478" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation affects albumin half-life and function.", "mechanism": "Lower albumin levels associated with MASLD.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12337478" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation impacts enzyme stability.", "mechanism": "Elevated GGT reflects liver injury and oxidative stress.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12337478" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Higher AST levels indicate hepatic dysfunction.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12337478" }, { "confidence": "low", "disease": "MASLD", "glycan_involvement": "Glycosylation influences enzyme secretion.", "mechanism": "Elevated ALT is a marker of liver injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12337478" }, { "confidence": "high", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Glycosylation stabilizes PDL1 and modulates its immune checkpoint function.", "mechanism": "Upregulated in trained hBMSC, mediates immunosuppression and reduces liver inflammation.", "protein": "PDL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337527" }, { "confidence": "high", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Glycosylation affects IDO1 secretion and stability.", "mechanism": "IDO1 upregulation in trained hBMSC promotes anti-inflammatory macrophage polarization and immune tolerance.", "protein": "IDO1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates immune cell signaling.", "mechanism": "Reduced CD45+ immune cell infiltration in T-hBMSC-treated livers indicates decreased inflammation.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337527" }, { "confidence": "high", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Glycosylation required for ligand binding and scavenger function.", "mechanism": "Increased F4/80+CD163+ (M2) macrophages in T-hBMSC-treated livers promote resolution of inflammation.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "protective", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "N-glycosylation modulates T cell costimulation.", "mechanism": "Decreased CD86+ (M1) macrophages after T-hBMSC treatment reflect reduced pro-inflammatory response.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "C-type lectin; glycosylation critical for ligand recognition.", "mechanism": "Increased CD206+ (M2) macrophages after T-hBMSC treatment support anti-inflammatory tissue repair.", "protein": "CD206", "relationship_type": "protective", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Reduced IL6 levels after T-hBMSC treatment indicate decreased systemic inflammation.", "protein": "IL6", "relationship_type": "biomarker", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "O-glycosylation modulates chemokine activity.", "mechanism": "Lower IL8 expression in T-hBMSC-treated mice reflects reduced neutrophil recruitment.", "protein": "IL8", "relationship_type": "biomarker", "source_pmcid": "PMC12337527" }, { "confidence": "high", "disease": "Fulminant hepatic failure (FHF)", "glycan_involvement": "Glycosylation influences secretion and receptor interaction.", "mechanism": "TNF-\u03b1 is a key driver of inflammatory liver injury; its signaling is downregulated by T-hBMSC.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337527" }, { "confidence": "medium", "disease": "Allograft rejection", "glycan_involvement": "Glycosylation required for immune checkpoint function.", "mechanism": "PDL1 upregulation in T-hBMSC may reduce immune-mediated allograft rejection.", "protein": "PDL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337527" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "MBL2 is a glycosylated lectin; glycosylation affects its stability and immune function.", "mechanism": "Elevated plasma MBL2 associated with unfavorable outcomes (reduced distant metastasis-free survival and OS) after NAC.", "protein": "MBL2", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "P4HB is N-glycosylated, which modulates its chaperone activity and secretion.", "mechanism": "High plasma P4HB levels linked to poor prognosis and reduced survival post-NAC.", "protein": "P4HB", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "APOC3 is O-glycosylated, influencing lipid metabolism and inflammation.", "mechanism": "Plasma APOC3 levels correlated with pCR and long-term outcomes in NAC-treated patients.", "protein": "APOC3", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "ENG is heavily glycosylated; glycosylation regulates its cell-surface expression and TGF-beta signaling.", "mechanism": "Plasma ENG levels associated with pCR and prognosis after NAC.", "protein": "ENG", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "GLUT1 is N-glycosylated, which is essential for its membrane localization and glucose transport.", "mechanism": "GLUT1 overexpression correlated with poor NAC response and reduced relapse-free survival.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "GLUT3 is N-glycosylated, affecting its stability and transport activity.", "mechanism": "GLUT3 expression associated with poor NAC response and prognosis.", "protein": "GLUT3", "protein_enriched": { "function": "Facilitative glucose transporter (PubMed:26176916, PubMed:32860739, PubMed:9477959). Can also mediate the uptake of various other monosaccharides across the cell membrane (PubMed:26176916, PubMed:9477", "gene_name": "SLC2A3", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P11169" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "CAIX is N-glycosylated; glycosylation modulates its cell-surface stability and enzymatic activity.", "mechanism": "CAIX expression linked to hypoxia, poor NAC response, and reduced relapse-free survival.", "protein": "Carbonic anhydrase IX", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "CD10 is N-glycosylated, which affects its protease activity and cell interactions.", "mechanism": "CD10-expressing CAFs promote chemoresistance via stearoyl-CoA desaturase-mediated lipid metabolism.", "protein": "CD10", "protein_enriched": { "function": "Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhi", "gene_name": "CD72", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX" ], "uniprot_id": "P21854" }, "relationship_type": "causal", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "SLC7A5 is glycosylated, influencing its transporter function.", "mechanism": "SLC7A5 upregulation in non-pCR tumors and metastases; associated with NAC resistance.", "protein": "SLC7A5", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation (conjugation with glycine) is essential for bile acid function and signaling.", "mechanism": "Higher plasma glycohyocholic acid levels associated with favorable OS and NAC response.", "protein": "Glycohyocholic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12337530" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "GDF15 is a glycoprotein; glycosylation required for secretion and stability.", "mechanism": "Pharmacological (high) levels of GDF15 reduce body weight and food intake in obese mice.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation affects secretion and bioactivity.", "mechanism": "Pharmacological (high) levels of FGF21 reduce body weight, mainly via increased energy expenditure.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "Pharmacological GDF15 improves glucose tolerance and lowers fasting insulin in obese mice.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Pharmacological FGF21 lowers fasting insulin and may improve insulin sensitivity.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "medium", "disease": "Cancer Cachexia", "glycan_involvement": "Glycosylation supports secretion; not directly linked to cachexia mechanism.", "mechanism": "Pathologically high GDF15 levels cause chronic weight loss (cachexia) in cancer.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "causal", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Fatty Liver Disease", "glycan_involvement": "Glycosylation required for secretion and hepatic targeting.", "mechanism": "Pharmacological FGF21 reduces hepatic fat content in obese mice.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Fatty Liver Disease", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Pharmacological GDF15 (alone or with FGF21) reduces liver fat in obese mice.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337615" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation enables detection in plasma.", "mechanism": "Endogenous GDF15 levels rise in obesity but are not sufficient to prevent weight gain.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337615" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation enables detection in plasma.", "mechanism": "Endogenous FGF21 levels rise in obesity but are not sufficient to prevent weight gain.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337615" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation required for normal function; not directly tested.", "mechanism": "Genetic deletion of GDF15 may slightly increase weight gain in male mice on high-fat diet.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "protective", "source_pmcid": "PMC12337615" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "IRE1\u03b1 is a glycoprotein; ER stress and glycoprotein folding are central to its activation.", "mechanism": "IRE1\u03b1 hyper-activation induces terminal UPR and apoptosis in breast cancer cells, suppressing tumor growth.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337650" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "ER stress from glycoprotein misfolding triggers IRE1\u03b1 pathway.", "mechanism": "Mn2+ hyper-activates IRE1\u03b1, leading to increased apoptosis and reduced TNBC cell viability.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337650" }, { "confidence": "high", "disease": "Tumor progression", "glycan_involvement": "XBP1s regulates genes involved in glycoprotein folding and secretion.", "mechanism": "XBP1s expression correlates with tumor malignancy and poor survival; adaptive UPR supports tumor growth.", "protein": "XBP1", "protein_enriched": { "function": "Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic devel", "gene_name": "XBP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P17861" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "Chemotherapy resistance", "glycan_involvement": "Glycoprotein folding stress activates IRE1\u03b1.", "mechanism": "IRE1\u03b1-XBP1 pathway enables tumor cells to adapt to ER stress induced by chemotherapy.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "Metastasis", "glycan_involvement": "Glycoprotein homeostasis is regulated by IRE1\u03b1.", "mechanism": "IRE1\u03b1-XBP1 signaling facilitates tumor cell adaptation and metastasis.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "Angiogenesis", "glycan_involvement": "Glycoprotein folding and secretion are involved in angiogenic signaling.", "mechanism": "IRE1\u03b1-XBP1 pathway promotes angiogenesis in tumors under ER stress.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "high", "disease": "ER stress-related apoptosis", "glycan_involvement": "ER stress from glycoprotein misfolding is the trigger.", "mechanism": "Hyper-activation of IRE1\u03b1 triggers RIDD and JNK pathways, leading to apoptosis.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "Protein misfolding disorders", "glycan_involvement": "BIP is an ER-resident glycoprotein chaperone.", "mechanism": "BIP upregulation marks ER stress and UPR activation.", "protein": "BIP (HSPA5)", "relationship_type": "biomarker", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "ER stress-related apoptosis", "glycan_involvement": "TRAF2 is a glycoprotein adaptor in the apoptotic pathway.", "mechanism": "IRE1\u03b1-TRAF2 interaction activates JNK, promoting apoptosis under ER stress.", "protein": "TRAF2", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis (PubMed:10346818, PubMed:11784851, PubMed:12917689", "gene_name": "TRAF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q12933" }, "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "medium", "disease": "ER stress-related apoptosis", "glycan_involvement": "BLOS1 is a glycoprotein and RIDD substrate.", "mechanism": "IRE1\u03b1-dependent RIDD degrades BLOS1 mRNA, contributing to cell death under ER stress.", "protein": "BLOS1", "relationship_type": "causal", "source_pmcid": "PMC12337650" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b2 is a secreted glycoprotein; glycosylation is required for its secretion and activity.", "mechanism": "TGF-\u03b2 is a major profibrotic cytokine that activates hepatic stellate cells and promotes ECM deposition.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12337869" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "\u03b1-SMA marks activation of hepatic stellate cells into myofibroblasts, a key event in fibrogenesis.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects its stability and secretion.", "mechanism": "TNF-\u03b1 is a pro-inflammatory cytokine that activates hepatic stellate cells and promotes inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "IL-6 is glycosylated, which modulates its receptor binding and activity.", "mechanism": "IL-6 mediates inflammation and can promote fibrogenesis under chronic conditions.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "ALP is elevated in cholestasis and biliary obstruction; reduction indicates improved biliary function.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Albumin is glycosylated; glycan modifications can affect its function and clearance.", "mechanism": "Serum albumin levels reflect liver synthetic function; hypoalbuminemia is common in advanced liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Oxidative stress injury", "glycan_involvement": "GPx is glycosylated, which is important for its secretion and activity.", "mechanism": "GPx detoxifies peroxides; decreased activity indicates oxidative stress in liver injury.", "protein": "GPx", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation required for TGF-\u03b2 maturation and function.", "mechanism": "Persistent TGF-\u03b2 signaling drives progression from fibrosis to cirrhosis.", "protein": "TGF-\u03b2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Biliary obstruction", "glycan_involvement": "Glycosylation affects ALP isoform distribution in serum.", "mechanism": "ALP is elevated in biliary obstruction; normalization indicates resolution.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12337869" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor interaction.", "mechanism": "TNF-\u03b1 promotes hepatic stellate cell activation and fibrogenesis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337869" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects ligand binding and stability.", "mechanism": "PD-1 blockade enhances antitumor immunity and restricts HCC growth.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337885" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation of PD-L1 regulates its stability and immune checkpoint function.", "mechanism": "PD-L1 binds PD-1 to suppress T-cell activity, promoting immune evasion in HCC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation modulates CTLA-4 surface expression and function.", "mechanism": "CTLA-4 inhibits T-cell activation, contributing to immune suppression in HCC.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337885" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "GPX4 protects against ferroptosis; its depletion induces ferroptotic cell death in HCC.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CRT is a glycoprotein; glycosylation may affect its chaperone and immune functions.", "mechanism": "Surface exposure of CRT is a hallmark of immunogenic cell death, promoting antitumor immunity.", "protein": "CRT", "relationship_type": "biomarker", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Not glycosylated.", "mechanism": "HMGB-1 release signals immunogenic cell death, enhancing immune response against HCC.", "protein": "HMGB-1", "relationship_type": "biomarker", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD8 is N-glycosylated; glycosylation modulates T cell receptor interactions.", "mechanism": "CD8+ T cell infiltration correlates with effective antitumor immunity in HCC.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD25 is N-glycosylated; glycosylation affects receptor function.", "mechanism": "CD25 marks regulatory T cells (Tregs), which suppress antitumor immunity in HCC.", "protein": "CD25", "relationship_type": "biomarker", "source_pmcid": "PMC12337885" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD49b is N-glycosylated; glycosylation modulates cell adhesion.", "mechanism": "CD49b marks NK cells; increased infiltration is associated with tumor cell killing.", "protein": "CD49b", "relationship_type": "biomarker", "source_pmcid": "PMC12337885" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "N-glycosylation of PD-L1 is essential for its stability and immune checkpoint function.", "mechanism": "PD-L1 expression on tumor cells leads to T cell suppression and immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12337885" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for proper folding, stability, and function in cell adhesion.", "mechanism": "Promotes monocyte adhesion and recruitment to endothelium, driving inflammation and plaque formation.", "protein": "ICAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337887" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates ligand binding and cell-cell interactions.", "mechanism": "Facilitates monocyte and lymphocyte adhesion to activated endothelium, contributing to plaque development.", "protein": "VCAM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337887" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation essential for ligand recognition and leukocyte binding.", "mechanism": "Mediates rolling and adhesion of leukocytes to endothelium during inflammation.", "protein": "SELE (E-selectin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337887" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Indirect; regulates glycoprotein expression but is not glycosylated.", "mechanism": "Drives transcription of adhesion molecules and inflammatory cytokines, promoting vascular inflammation.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "causal", "source_pmcid": "PMC12337887" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Induces endothelial activation, upregulates adhesion molecules, and amplifies inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12337887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Promotes inflammatory cell recruitment and cytokine cascade in plaques.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12337887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Drives chronic inflammation and acute phase response in vascular tissue.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12337887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation influences surface expression and immune signaling.", "mechanism": "Marker of M1 macrophage polarization, associated with pro-inflammatory state in plaques.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12337887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation critical for ligand binding and endocytosis.", "mechanism": "Marker of M2 macrophage polarization, associated with anti-inflammatory and tissue repair functions.", "protein": "CD206 (MRC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12337887" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation affects secretion and enzymatic activity.", "mechanism": "Degrades extracellular matrix, contributing to plaque instability and rupture.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12337887" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "PI-88 glycan motifs mimic heparan sulfate, blocking VEGF binding.", "mechanism": "PI-88 inhibits VEGF-mediated angiogenesis by binding VEGF and preventing its interaction with receptors.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "PI-88 glycan motifs mimic heparan sulfate, blocking FGF binding.", "mechanism": "PI-88 inhibits FGF-mediated angiogenesis by binding FGF and preventing its interaction with receptors.", "protein": "Fibroblast Growth Factor (FGF)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PI-88 glycan motifs act as heparanase inhibitors.", "mechanism": "PI-88 inhibits heparanase, preventing degradation of extracellular matrix and release of angiogenic growth factors.", "protein": "Heparanase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "PI-88 glycan motifs inhibit heparanase activity.", "mechanism": "Inhibition of heparanase by PI-88 reduces tumor recurrence post-resection.", "protein": "Heparanase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "PI-88 glycan motifs interfere with VEGF signaling.", "mechanism": "VEGF-driven angiogenesis is a key process in tumor growth; PI-88 blocks this pathway.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "PI-88 glycan motifs interfere with FGF signaling.", "mechanism": "FGF-driven angiogenesis supports tumor growth; PI-88 blocks this pathway.", "protein": "Fibroblast Growth Factor (FGF)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12337991" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "GLP1R is a glycoprotein; glycosylation affects receptor trafficking and ligand binding.", "mechanism": "GLP1R agonists improve glycemic control by enhancing insulin secretion.", "protein": "GLP1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Semaglutide is a glycopeptide analog of GLP-1; glycosylation increases stability.", "mechanism": "Semaglutide (GLP1-RA) reduces appetite and body weight.", "protein": "Semaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338108" }, { "confidence": "medium", "disease": "VTE", "glycan_involvement": "Glycosylation of semaglutide prolongs half-life, possibly affecting risk profile.", "mechanism": "GLP1-RA use is associated with increased risk of venous thromboembolism.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "medium", "disease": "PVT", "glycan_involvement": "Glycosylation of semaglutide may influence pharmacokinetics and adverse event risk.", "mechanism": "Case report links semaglutide initiation to development of portal vein thrombosis.", "protein": "Semaglutide", "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "PVT", "glycan_involvement": "VWF is heavily glycosylated; glycosylation modulates its pro-thrombotic activity.", "mechanism": "JAK2 mutation increases endothelial VWF expression, promoting thrombosis.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "PVT", "glycan_involvement": "P-selectin glycosylation is essential for its cell adhesion function.", "mechanism": "JAK2 mutation upregulates P-selectin, enhancing platelet-endothelial interactions.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "Protein C deficiency", "glycan_involvement": "Protein C is glycosylated; glycosylation affects secretion and anticoagulant activity.", "mechanism": "Protein C deficiency is a risk factor for thrombophilia and PVT.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "VTE", "glycan_involvement": "Glycosylation regulates VWF multimerization and function.", "mechanism": "Elevated VWF promotes venous thromboembolism.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates receptor function and drug response.", "mechanism": "GLP1R agonists induce satiety and weight loss.", "protein": "GLP1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Glycosylation enhances drug stability and efficacy.", "mechanism": "Semaglutide improves glycemic control in T2DM.", "protein": "Semaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338108" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "N-glycosylation modulates HER2 stability and signaling.", "mechanism": "HER2 overexpression drives tumor growth; targeted by tucatinib to inhibit proliferation.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338185" }, { "confidence": "medium", "disease": "Cardiac dysfunction (EF decreased)", "glycan_involvement": "Glycosylation affects HER2 receptor function in cardiac tissue.", "mechanism": "HER2 signaling is essential for cardiac myocyte survival; inhibition by tucatinib can reduce ejection fraction.", "protein": "HER2 (ERBB2)", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "medium", "disease": "Skin toxicity", "glycan_involvement": "EGFR glycosylation regulates receptor trafficking and signaling in skin.", "mechanism": "EGFR inhibition disrupts epithelial cell growth and repair, leading to skin/nail adverse events.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Glycosylation modulates HER2 function in neural tissue.", "mechanism": "HER2 inhibition affects neural cell growth and survival, contributing to neuropathy.", "protein": "HER2 (ERBB2)", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation affects HER2 receptor stability in hepatocytes.", "mechanism": "HER2 inhibition may impair liver cell signaling, leading to elevated ALT/AST and liver injury.", "protein": "HER2 (ERBB2)", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation is critical for platelet glycoprotein function.", "mechanism": "Disruption of hematopoietic stem cell signaling by HER2/EGFR inhibition may reduce platelet production.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "low", "disease": "Brain edema", "glycan_involvement": "VEGF glycosylation modulates vascular permeability.", "mechanism": "HER2/EGFR inhibition may alter VEGF-mediated angiogenesis, contributing to cerebral edema.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "medium", "disease": "Paronychia", "glycan_involvement": "Glycosylation regulates epithelial cell adhesion and repair.", "mechanism": "EGFR/HER2 inhibition impairs epithelial repair, leading to nail fold inflammation.", "protein": "Skin/mucosal epithelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "high", "disease": "Metastatic breast cancer", "glycan_involvement": "N-glycosylation influences HER2 dimerization and signaling.", "mechanism": "HER2 overexpression is a driver of metastasis; targeted by tucatinib for therapy.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338185" }, { "confidence": "low", "disease": "Brain edema", "glycan_involvement": "Glycosylation affects albumin stability and function.", "mechanism": "Low albumin due to malnutrition or liver dysfunction may contribute to cerebral edema.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12338185" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation affects h-CRP stability and function.", "mechanism": "Elevated h-CRP reflects systemic inflammation in ALD; reduced by probiotic therapy.", "protein": "h-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "N-glycosylation modulates IL-6 secretion and activity.", "mechanism": "IL-6 is upregulated in ALD and reduced by probiotics, indicating inflammation modulation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation influences IL-1\u03b2 maturation and secretion.", "mechanism": "IL-1\u03b2 is increased in ALD and reduced by probiotics, reflecting decreased hepatic inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding and stability.", "mechanism": "TNF-\u03b1 is elevated in ALD and reduced by probiotics, indicating reduced inflammatory signaling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation modulates ALT stability and serum half-life.", "mechanism": "ALT is a marker of hepatocellular injury; decreased by probiotic therapy.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation affects AST secretion and activity.", "mechanism": "AST is a marker of liver injury; reduced by probiotics.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "high", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycosylation is essential for GGT enzymatic activity.", "mechanism": "GGT is elevated in ALD and reduced by probiotics, indicating improved liver function.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12338215" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Bacterial glycoproteins mediate host-microbe interactions and mucosal adhesion.", "mechanism": "Increased Bifidobacteria abundance correlates with improved gut barrier and reduced liver inflammation.", "protein": "Bifidobacterium surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12338215" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Bacterial glycoproteins facilitate immune modulation and barrier function.", "mechanism": "Increased Lactobacilli abundance improves gut flora and reduces hepatic inflammation.", "protein": "Lactobacillus surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12338215" }, { "confidence": "medium", "disease": "Alcoholic Liver Disease (ALD)", "glycan_involvement": "Glycoproteins mediate pathogenicity and host interaction.", "mechanism": "Elevated Enterococci abundance is associated with worsened ALD; reduced by probiotics.", "protein": "Enterococcus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338215" }, { "confidence": "high", "disease": "Hypertensive heart disease", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function as an inflammatory marker", "mechanism": "Elevated CRP increases risk of hypertensive heart disease by 21%", "protein": "C-reactive protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12338239" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "CRP glycosylation not directly implicated in MI risk", "mechanism": "No causal link found between serum CRP and myocardial infarction risk", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12338239" }, { "confidence": "high", "disease": "Coronary heart disease", "glycan_involvement": "CRP glycosylation not directly implicated in CHD risk", "mechanism": "No causal link found between serum CRP and coronary heart disease risk", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12338239" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease", "glycan_involvement": "LDL particles contain apolipoprotein B, a glycoprotein; glycosylation may affect LDL metabolism", "mechanism": "LDL is a causal factor in atherosclerosis development", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12338239" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "IgG N-glycosylation modulates immune function; not causally linked to IS in MR", "mechanism": "MR analysis found no strong evidence for causal link between genetically determined IgG N-glycosylation and ischemic stroke", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (tested, not supported)", "source_pmcid": "PMC12338239" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Rheumatoid factor is an autoantibody; glycosylation may affect its immunogenicity", "mechanism": "Rheumatoid factor may be associated with adverse prognosis in IS patients", "protein": "Rheumatoid factor", "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12338239" }, { "confidence": "low", "disease": "Frozen Shoulder", "glycan_involvement": "IgG glycosylation may modulate immune-mediated tissue injury", "mechanism": "IS patients have increased risk of Frozen Shoulder; possible immune involvement", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk factor", "source_pmcid": "PMC12338239" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "ApoB glycosylation may affect LDL clearance and diabetes risk", "mechanism": "LDL levels associated with T2DM risk", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk marker", "source_pmcid": "PMC12338239" }, { "confidence": "low", "disease": "Alzheimer disease", "glycan_involvement": "IgG N-glycosylation modulates immune response in AD", "mechanism": "Altered IgG glycosylation may contribute to neuroinflammation in AD", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk factor (immunological)", "source_pmcid": "PMC12338239" }, { "confidence": "low", "disease": "Alzheimer disease", "glycan_involvement": "CRP glycosylation affects its inflammatory activity", "mechanism": "CRP as an inflammatory marker may be associated with AD risk", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12338239" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation of HLA complexes affects antigen presentation and immune response.", "mechanism": "Proteobacteria (including Gammaproteobacteria) increase melanoma risk via immune modulation; melanoma cells present bacteria-derived HLA peptides.", "protein": "Proteobacteria-derived HLA-I/II peptide complexes", "relationship_type": "causal", "source_pmcid": "PMC12338303" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Biofilm matrix proteins are glycosylated, influencing biofilm stability and immune evasion.", "mechanism": "Esp degrades S. aureus biofilm proteins, reducing pathogenic colonization and inflammation, indirectly protecting against melanoma.", "protein": "Staphylococcus epidermidis Esp (glutamyl endopeptidase)", "relationship_type": "protective", "source_pmcid": "PMC12338303" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "No direct glycosylation, but may interact with glycoprotein receptors on tumor cells.", "mechanism": "Metabolite selectively inhibits tumor cell proliferation and suppresses melanoma growth.", "protein": "Staphylococcus-derived 6-N-hydroxyaminopurine", "relationship_type": "protective", "source_pmcid": "PMC12338303" }, { "confidence": "medium", "disease": "Basal cell carcinoma (BCC)", "glycan_involvement": "Biofilm glycoproteins mediate adhesion and immune evasion; aberrant glycosylation may promote carcinogenesis.", "mechanism": "Skin-colonizing Bacteroidetes increase BCC risk, possibly via biofilm formation and aberrant glycosylation.", "protein": "Bacteroidetes biofilm glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Peptide glycosylation enhances antimicrobial activity and stability.", "mechanism": "Synergize with LL-37 to inhibit S. aureus and reduce inflammation, lowering melanoma risk.", "protein": "Staphylococcus hominis antimicrobial peptides", "relationship_type": "protective", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "LL-37 is glycosylated, affecting its antimicrobial and immunomodulatory functions.", "mechanism": "Potentiated by staphylococcal peptides, LL-37 inhibits pathogenic bacteria and modulates immune response.", "protein": "Human cathelicidin LL-37", "relationship_type": "protective", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Surface glycoproteins mediate immune cell interactions.", "mechanism": "Associated with increased CD8+ T cell infiltration in melanoma, potentially affecting prognosis.", "protein": "Acinetobacter surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Glycopeptides presented by HLA complexes influence immune recognition.", "mechanism": "More abundant in melanoma; may infiltrate tumor cells and modulate immune presentation.", "protein": "Enterobacteriaceae-derived glycopeptides", "relationship_type": "causal", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Skin cancer (general)", "glycan_involvement": "Enzyme glycosylation affects activity and host interactions.", "mechanism": "Exoenzymes facilitate host cell invasion and immune evasion, contributing to carcinogenesis.", "protein": "Staphylococcus aureus exoenzymes", "relationship_type": "causal", "source_pmcid": "PMC12338303" }, { "confidence": "low", "disease": "Melanoma", "glycan_involvement": "Glycosylation of matrix proteins modulates biofilm integrity and immune response.", "mechanism": "Biofilm formation by commensal staphylococci inhibits pathogenic colonization and inflammation.", "protein": "Staphylococcus epidermidis biofilm matrix proteins", "relationship_type": "protective", "source_pmcid": "PMC12338303" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "ApoB is N-glycosylated, affecting its secretion and lipid binding.", "mechanism": "Elevated ApoB levels are associated with increased triglycerides in bipolar disorder patients.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "ApoA1 is glycosylated, influencing HDL assembly.", "mechanism": "ApoA1 levels are measured but not significantly different between groups; involved in HDL formation.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12338329" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "HDL contains glycoproteins (ApoA1, ApoA2) whose glycosylation affects HDL function.", "mechanism": "Lower HDL is a protective factor against hypertriglyceridemia in bipolar disorder.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "CETP is N-glycosylated, which modulates its activity.", "mechanism": "CETP mediates exchange of cholesteryl esters and triglycerides between HDL and ApoB-containing lipoproteins, lowering HDL and raising TG.", "protein": "Cholesteryl Ester Transfer Protein (CETP)", "relationship_type": "causal", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation of ApoB affects LDL/VLDL metabolism.", "mechanism": "Elevated ApoB and TG increase risk of atherosclerosis in bipolar disorder patients.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "causal", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-inflammatory function.", "mechanism": "Low HDL reduces anti-inflammatory and antioxidant protection, increasing atherosclerosis risk.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation affects ApoB secretion and lipid metabolism.", "mechanism": "Elevated ApoB and TG are associated with increased diabetes prevalence in bipolar disorder.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Hypertriglyceridemia", "glycan_involvement": "VLDL contains glycoproteins (ApoB), glycosylation affects secretion.", "mechanism": "Increased BMI leads to more VLDL synthesis, raising plasma TG.", "protein": "Very Low-Density Lipoprotein (VLDL)", "relationship_type": "causal", "source_pmcid": "PMC12338329" }, { "confidence": "medium", "disease": "Mixed Hyperlipidemia", "glycan_involvement": "N-glycosylation modulates CETP function.", "mechanism": "CETP activity leads to simultaneous elevation of TG and cholesterol.", "protein": "Cholesteryl Ester Transfer Protein (CETP)", "relationship_type": "causal", "source_pmcid": "PMC12338329" }, { "confidence": "low", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation of HDL proteins influences anti-inflammatory properties.", "mechanism": "Low HDL and high TG increase risk of pancreatitis in bipolar disorder.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12338329" }, { "confidence": "high", "disease": "Candidiasis (biofilm-associated)", "glycan_involvement": "N-acetylglucosamine used for cell wall glycoprotein synthesis; glycosylation critical for structure/function.", "mechanism": "Cell wall glycoproteins are essential for biofilm formation, virulence, and protection against host defenses.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "high", "disease": "Drug-resistant Candida infections", "glycan_involvement": "Glycosylation of cell wall proteins enhances biofilm robustness.", "mechanism": "Glycoproteins contribute to biofilm matrix, increasing resistance to antifungals.", "protein": "Candida krusei cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "high", "disease": "Candidiasis (biofilm-associated)", "glycan_involvement": "Glucose and galactose residues in glycoproteins increase stress and drug resistance.", "mechanism": "Cell wall glycoproteins mediate adhesion and biofilm formation.", "protein": "Candida glabrata cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Candidiasis (biofilm-associated)", "glycan_involvement": "Recognition of glycosylated compounds (e.g., glycometronidazole) facilitates drug entry.", "mechanism": "Glycoreceptors mediate uptake of glycosylated drugs into biofilms.", "protein": "Glycoreceptors (fungal)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Drug-resistant Candida infections", "glycan_involvement": "Glycosylation may affect P-gp function and substrate specificity.", "mechanism": "Efflux of antifungal drugs, contributing to resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "low", "disease": "Candidiasis (biofilm-associated)", "glycan_involvement": "Indirect; glycosylation status may affect enzyme activity.", "mechanism": "Biofilm metabolic activity measured via dehydrogenase activity.", "protein": "Dehydrogenase enzyme (mitochondrial, XTT assay)", "relationship_type": "biomarker", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Vulvovaginal candidiasis", "glycan_involvement": "Glycosylation essential for adhesion and immune evasion.", "mechanism": "Glycoproteins mediate adhesion to mucosal surfaces.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Oropharyngeal candidiasis", "glycan_involvement": "Glycan modifications promote tissue adherence.", "mechanism": "Glycoproteins facilitate colonization of oral mucosa.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Esophageal candidiasis", "glycan_involvement": "Glycosylation supports invasive growth.", "mechanism": "Glycoproteins enable invasion of esophageal tissue.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Onychomycosis", "glycan_involvement": "Glycosylation aids in environmental resistance.", "mechanism": "Glycoproteins contribute to nail infection and persistence.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12338862" }, { "confidence": "medium", "disease": "Central nervous system diseases", "glycan_involvement": "N-glycosylation modulates immune recognition and half-life.", "mechanism": "Enriched in CSF-derived EVs; may reflect CNS disease-associated inflammation.", "protein": "Alpha-1-acid glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "N-glycosylation affects receptor binding and CNS transport.", "mechanism": "Altered levels in CSF-EVs may indicate neurodegeneration.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences protease inhibitor activity.", "mechanism": "Associated with amyloid clearance; detected in CSF-EVs.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates chaperone function.", "mechanism": "Clusterin in CSF-EVs is linked to amyloid pathology.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects lipid binding and aggregation.", "mechanism": "APOE isoforms in CSF-EVs are associated with AD risk.", "protein": "Apolipoprotein E", "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "medium", "disease": "CNS inflammation", "glycan_involvement": "N-glycosylation modulates solubility and transport.", "mechanism": "Elevated CSF-EV albumin may reflect blood-brain barrier disruption.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation influences lipid transport.", "mechanism": "Altered levels in CSF-EVs may indicate demyelination.", "protein": "Apolipoprotein A1", "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "low", "disease": "CNS tumors", "glycan_involvement": "N-glycosylation modulates immune interactions.", "mechanism": "Detected in CSF-EVs; may reflect tumor-associated changes.", "protein": "Apolipoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "low", "disease": "CNS trauma", "glycan_involvement": "N-glycosylation affects heme binding.", "mechanism": "Increased in CSF-EVs after CNS injury.", "protein": "Hemopexin", "protein_enriched": { "function": "Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation", "gene_name": "HPX", "glycan_count": 236, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G00875VP", "G00912UN", "G01650EU", "G02528FI", "G02886BB", "G04657PL", "G04854VP", "G05933EN", "G06247RL", "G06356OH", "G06853GH", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G14572XX", "G14994KB", "G15169WU", "G18647XP", "G20425TQ", "G22140GZ", "G22276PO", "G22310AV", "G22572EH", "G23294PN", "G23863VK", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G30769VJ", "G31118FR", "G31916IQ", "G36131WL", "G37818NZ", "G37868ZX", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G42358LZ", "G43223CG", "G44576HQ", "G45395BF", "G45504EY", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G47702MW", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55412XP", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G62165AG", "G63980BQ", "G64394MX", "G65019XG", "G66163OV", "G66621EA", "G68735SN", "G70232NH", "G70375MX", "G70619PT", "G70888PK", "G72291OX", "G72747WU", "G72797UR", "G74772YG", "G75983OB", "G76417NN", "G78644BR", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82463GQ", "G82830MN", "G83555HU", "G84452RH", "G85144OK", "G86056PA", "G86182NS", "G86234IN", "G86752LQ", "G86795LJ", "G86880BF", "G87399DK", "G88374WZ", "G89205CJ", "G90093AU", "G90659AW", "G92135MA", "G92275SC", "G92406TI", "G94470IW", "G94917XT", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G00273SJ", "G14669DU", "G22768VO", "G60861FA", "G77669RF", "G89045VA", "G92551JA", "G57321FI", "G42962KI", "G44215PV", "G46687AB", "G60923RB", "G71146HJ", "G17015OC", "G29931IJ", "G43417UB", "G74722FL", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G01485JJ", "G02030ZB", "G10819WX", "G12745LE", "G14547CB", "G14972EH", "G15127JD", "G20528HD", "G20706XG", "G25418HZ", "G26915XM", "G27915IV", "G30248BL", "G30970QQ", "G31852PQ", "G31986NC", "G33416PL", "G35253PZ", "G37412TK", "G37509XX", "G37692EO", "G37995HC", "G39619TI", "G41071NU", "G43669FQ", "G43734MM", "G46524LG", "G54010QB", "G56284ZY", "G58087IP", "G58954YZ", "G60834IK", "G61256FT", "G62461SM", "G63381RX", "G67164EE", "G69521XL", "G71463BG", "G72398FA", "G72787SB", "G75798PH", "G76329HL", "G77547TA", "G78502KD", "G81124ET", "G81295CK", "G85269DF", "G85554PZ", "G85677PP", "G87389XI", "G89098OM", "G92081HT", "G98129XB", "G01160VV", "G05049YU", "G05724UK", "G05962QB", "G07246CJ", "G07755XJ", "G11911BT", "G12341GU", "G12579WK", "G15038BD", "G15664MX", "G17208MA", "G23505EP", "G30740WO", "G34989PA", "G35029YA", "G39188ZX", "G40206WX", "G41247ZX", "G44753VC", "G47950XN", "G49018RC", "G49642SA", "G49906RN", "G49955PK", "G56307ZW", "G59324HL", "G62765YT", "G64275UO", "G64527OM", "G68490OW", "G70101JE", "G70441OD", "G72790NZ", "G75418YA", "G76295SF", "G80920RR", "G83646BJ", "G84225JN", "G85282JO", "G87661QW", "G90734RJ", "G95977AE", "G96430BV" ], "uniprot_id": "P02790" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation modulates chaperone activity.", "mechanism": "Detected in CSF-EVs; may reflect neurodegeneration.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339045" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Elevated GGT reflects hepatic steatosis and oxidative stress, associated with insulin resistance in T2DM.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Prothrombin glycosylation is essential for secretion and function.", "mechanism": "Hyperglycemia increases prothrombin synthesis, promoting a procoagulant state in T2DM.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Albumin glycosylation modulates half-life and renal handling.", "mechanism": "Low serum albumin indicates poor renal function and is more frequent in T2DM with CKD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may affect albumin's antioxidant properties.", "mechanism": "Low serum albumin is associated with increased stroke risk and poor outcomes in T2DM.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "Immunoglobulin glycosylation affects serum protein levels and immune function.", "mechanism": "Elevated total serum protein in T2DM with lymphoma due to immunoglobulin overproduction.", "protein": "Total Serum Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation regulates GGT membrane localization and activity.", "mechanism": "Elevated GGT is linked to oxidative stress and glutathione metabolism in HF with T2DM.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation of coagulation factors influences INR.", "mechanism": "INR abnormalities reflect coagulation disturbances in T2DM with HF.", "protein": "International Normalized Ratio (INR)", "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation of serum proteins affects vascular health.", "mechanism": "Abnormal total serum protein associated with stroke risk and outcomes in T2DM.", "protein": "Total Serum Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Fatty Liver Disease (FLD)", "glycan_involvement": "ALT glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT indicates liver cell damage in T2DM with FLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "AST glycosylation may modulate enzyme activity.", "mechanism": "Metformin therapy reduces AST abnormalities, indicating protective hepatic effects in T2DM.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339336" }, { "confidence": "high", "disease": "Viral infection (general)", "glycan_involvement": "O-GlcNAcylation is essential for MAVS activation.", "mechanism": "O-GlcNAcylation of MAVS at Ser366 promotes K63-linked ubiquitination, enhancing antiviral signaling and IFN-I production.", "protein": "MAVS", "protein_enriched": { "function": "Adapter required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:21170385, PubM", "gene_name": "MAVS", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G70994MS" ], "uniprot_id": "Q7Z434" }, "relationship_type": "causal", "source_pmcid": "PMC12339340" }, { "confidence": "high", "disease": "SAVI", "glycan_involvement": "Palmitoylation (lipidation) is critical; glycosylation not directly specified.", "mechanism": "Palmitoylation of STING is required for its oligomerization and IFN-I induction; inhibition of palmitoylation suppresses pathogenic STING activation in SAVI.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12339340" }, { "confidence": "high", "disease": "Viral infection (general)", "glycan_involvement": "Cell surface glycosylation required for receptor function.", "mechanism": "IFNAR, a glycoprotein receptor, mediates IFN-I signaling, modulating ISG expression and lipid metabolism to enhance antiviral defense.", "protein": "IFNAR", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Herpesvirus infection", "glycan_involvement": "Enzyme function; glycosylation not specified.", "mechanism": "CH25H produces 25-hydroxycholesterol, which restricts herpesvirus entry and replication.", "protein": "CH25H", "protein_enriched": { "function": "Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9092543", "gene_name": "CDC42BPA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41071NU" ], "uniprot_id": "Q5VT25" }, "relationship_type": "protective", "source_pmcid": "PMC12339340" }, { "confidence": "high", "disease": "Viral infection (general)", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "Glut1-mediated glucose uptake is essential for T cell activation and antiviral responses; deficiency impairs immunity.", "protein": "Glut1", "relationship_type": "causal", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Chronic viral infection (general)", "glycan_involvement": "Glycosylation supports membrane localization.", "mechanism": "AQP9 upregulation in CD8+ T cells supports memory formation via glycerol uptake and TAG synthesis.", "protein": "AQP9", "relationship_type": "protective", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Not specified.", "mechanism": "IRF3 deficiency impairs glucose homeostasis and promotes diabetes via dysregulation of adipocyte lipid genes.", "protein": "IRF3", "protein_enriched": { "function": "Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049", "gene_name": "IRF3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14653" }, "relationship_type": "causal", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Zika virus infection", "glycan_involvement": "Not specified.", "mechanism": "SREBP2 activation increases cholesterol synthesis, facilitating ZIKV replication; inhibition suppresses infection.", "protein": "SREBP2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Viral infection (general)", "glycan_involvement": "Glycosylation required for lysosomal trafficking.", "mechanism": "NPC1 mediates STING degradation; deficiency leads to STING accumulation and heightened IFN-I response.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "protective", "source_pmcid": "PMC12339340" }, { "confidence": "medium", "disease": "Viral infection (general)", "glycan_involvement": "N-glycosylation required for transporter function.", "mechanism": "ASCT2-mediated glutamine uptake is required for Th1/Th17 differentiation and antiviral immunity.", "protein": "ASCT2", "relationship_type": "causal", "source_pmcid": "PMC12339340" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "HDL particles are glycosylated, affecting their anti-inflammatory and cholesterol efflux functions.", "mechanism": "Low HDL-C levels and functional depletion are associated with increased mortality risk in ADHF via impaired anti-inflammatory defense and increased lipid deposition/oxidative stress.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "HDL glycosylation modulates its function; TyG index reflects metabolic status impacting glycoprotein function.", "mechanism": "Elevated TyG/HDL-C ratio independently predicts higher 30-day all-cause and cardiovascular mortality in ADHF, reflecting combined insulin resistance and impaired HDL function.", "protein": "TyG/HDL-C ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "NT-proBNP is N-glycosylated, affecting its stability and detection.", "mechanism": "NT-proBNP is a standard glycoprotein biomarker for heart failure severity and prognosis; predictive value is enhanced when combined with TyG/HDL-C ratio.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Albumin glycosylation status can affect its function and half-life.", "mechanism": "Low albumin (nutritional status) mediates part of the mortality risk associated with TyG/HDL-C ratio in ADHF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "low", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "GGT is glycosylated, which affects its enzymatic activity.", "mechanism": "GGT (oxidative stress marker) was tested as a mediator but showed no significant mediation effect for mortality risk in ADHF.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "high", "disease": "Cardiovascular Mortality", "glycan_involvement": "Glycosylation of HDL modulates its anti-atherogenic properties.", "mechanism": "Optimal HDL-C levels (1.0\u20131.5 mmol/L) are associated with lowest cardiovascular mortality risk; both low and high levels increase risk.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12339345" }, { "confidence": "high", "disease": "Cardiovascular Mortality", "glycan_involvement": "Reflects combined effects of glycoprotein function and metabolic status.", "mechanism": "High TyG/HDL-C ratio increases cardiovascular mortality risk in ADHF patients.", "protein": "TyG/HDL-C ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "medium", "disease": "Metabolic Dysfunction-Associated Fatty Liver Disease", "glycan_involvement": "HDL glycosylation affects lipid transport and anti-inflammatory function.", "mechanism": "Low HDL-C and high TyG/HDL-C ratio are associated with increased risk of fatty liver disease.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "medium", "disease": "Coronary Artery Calcification", "glycan_involvement": "Glycosylation modulates HDL particle function in vascular health.", "mechanism": "Low HDL-C and high TyG/HDL-C ratio predict increased risk of coronary artery calcification.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Cell surface glycoproteins on WBCs modulate immune response.", "mechanism": "Inflammatory pathway (WBC count) mediates part of the TyG/HDL-C ratio-associated mortality risk in ADHF.", "protein": "WBC markers", "relationship_type": "biomarker", "source_pmcid": "PMC12339345" }, { "confidence": "high", "disease": "Spontaneous hemothorax", "glycan_involvement": "Glycosylation is essential for P-glycoprotein function and drug transport.", "mechanism": "Fluconazole inhibits P-glycoprotein, increasing rivaroxaban exposure and bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12339356" }, { "confidence": "high", "disease": "Spontaneous hemothorax", "glycan_involvement": "N-glycosylation affects Factor Xa stability and activity.", "mechanism": "Rivaroxaban inhibits glycosylated Factor Xa, impairing coagulation and causing bleeding.", "protein": "Factor Xa", "relationship_type": "therapeutic target", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Bleeding events (general)", "glycan_involvement": "Glycosylation modulates ABCG2 transporter function.", "mechanism": "ABCG2 gene polymorphisms increase bleeding risk in rivaroxaban users.", "protein": "ABCG2", "relationship_type": "causal", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Bleeding events (general)", "glycan_involvement": "Glycosylation required for ABCB1 membrane localization and function.", "mechanism": "ABCB1 gene polymorphisms associated with increased bleeding risk on rivaroxaban.", "protein": "ABCB1", "relationship_type": "causal", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Spontaneous hemothorax", "glycan_involvement": "Glycosylation affects fibrinogen solubility and clot formation.", "mechanism": "Elevated fibrinogen and degradation products indicate ongoing bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Malignant pleural effusion (excluded)", "glycan_involvement": "CEA is highly glycosylated, affecting its detection and function.", "mechanism": "CEA used to rule out malignancy in pleural effusion.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Spontaneous hemothorax", "glycan_involvement": "Glycosylation required for antithrombin III activity.", "mechanism": "Rivaroxaban acts independently of antithrombin III, affecting coagulation.", "protein": "Antithrombin III", "relationship_type": "therapeutic target", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Malignant pleural effusion (excluded)", "glycan_involvement": "Glycosylation affects antigenicity and detection.", "mechanism": "Used to exclude squamous cell carcinoma in pleural effusion.", "protein": "Squamous cell carcinoma antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Malignant pleural effusion (excluded)", "glycan_involvement": "Glycosylation influences fragment stability and detection.", "mechanism": "Used to exclude carcinoma in pleural effusion.", "protein": "Cytokeratin 19 fragment", "relationship_type": "biomarker", "source_pmcid": "PMC12339356" }, { "confidence": "medium", "disease": "Malignant pleural effusion (excluded)", "glycan_involvement": "Glycosylation affects enzyme activity and immunoreactivity.", "mechanism": "Used to exclude neuroendocrine tumors in pleural effusion.", "protein": "Neuron-specific enolase", "relationship_type": "biomarker", "source_pmcid": "PMC12339356" }, { "confidence": "high", "disease": "NTRK gene fusion-positive cancer", "glycan_involvement": "N-glycosylation regulates TrkA cell surface expression and ligand binding.", "mechanism": "TrkA is activated by NTRK1 gene fusions, driving oncogenesis; inhibition suppresses tumor growth.", "protein": "TrkA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339406" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates TrkB receptor trafficking and signaling.", "mechanism": "BDNF-TrkB signaling regulates eating behavior and body weight; reduced TrkB leads to hyperphagia and obesity.", "protein": "TrkB", "relationship_type": "causal", "source_pmcid": "PMC12339406" }, { "confidence": "high", "disease": "NTRK gene fusion-positive cancer", "glycan_involvement": "N-glycosylation affects TrkC stability and function.", "mechanism": "TrkC activation via NTRK3 fusions drives tumorigenesis; inhibition is effective in treatment.", "protein": "TrkC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339406" }, { "confidence": "high", "disease": "Hypoalbuminemia", "glycan_involvement": "N-glycosylation is essential for albumin secretion and stability.", "mechanism": "Reduced serum albumin indicates impaired hepatic function in drug-induced liver injury.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Hepatocyte vacuolar degeneration", "glycan_involvement": "N-glycosylation affects fibrinogen secretion and clotting function.", "mechanism": "Elevated fibrinogen reflects hepatic dysfunction and inflammation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Splenic lymphocytopenia", "glycan_involvement": "O-glycosylation modulates CD45 signaling in lymphocytes.", "mechanism": "Reduced lymphocyte counts in spleen indicate immunosuppression due to Trk inhibition.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Cardiac arrhythmia", "glycan_involvement": "N-glycosylation required for hERG channel trafficking.", "mechanism": "hERG inhibition can cause QT prolongation and arrhythmia; LPM4870108 shows low risk.", "protein": "hERG potassium channel", "protein_enriched": { "function": "Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:185594", "gene_name": "KCNH2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q12809" }, "relationship_type": "causal", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Corneal inflammation", "glycan_involvement": "N-glycosylation affects TrkA localization in ocular tissues.", "mechanism": "Trk inhibition suppresses MEK signaling, leading to ocular inflammation.", "protein": "TrkA", "relationship_type": "causal", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Skin ulceration/scabbing", "glycan_involvement": "N-glycosylation modulates receptor function in sensory neurons.", "mechanism": "Trk inhibition impairs nociceptive signaling, increasing susceptibility to skin injury.", "protein": "TrkA/TrkB/TrkC", "relationship_type": "causal", "source_pmcid": "PMC12339406" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation required for albumin stability in circulation.", "mechanism": "Reduced albumin and mild anemia reflect hepatic and splenic extramedullary hematopoiesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339406" }, { "confidence": "high", "disease": "Aging-related metabolic disorders", "glycan_involvement": "Glycosylation affects IL-6 stability and secretion.", "mechanism": "IL-6 levels increase with aging and inflammation; beer consumption reduces IL-6, ameliorating aging-related inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates IL-15 bioactivity.", "mechanism": "Elevated IL-15 is linked to chronic inflammation in aging; beer reduces IL-15, lowering inflammatory burden.", "protein": "Interleukin-15 (IL-15)", "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation regulates TNF-\u03b1 receptor binding.", "mechanism": "TNF-\u03b1 is upregulated in aging and inflammation; beer consumption decreases TNF-\u03b1, reducing inflammation.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Oxidative stress injury", "glycan_involvement": "Glycosylation influences SOD stability.", "mechanism": "SOD activity is reduced in aging; beer increases SOD, protecting against oxidative stress.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Oxidative stress injury", "glycan_involvement": "Glycosylation affects CAT activity.", "mechanism": "CAT activity declines with age; beer restores CAT activity, reducing oxidative damage.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Oxidative stress injury", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "GSH-Px is decreased in aging; beer increases GSH-Px, mitigating oxidative stress.", "protein": "Glutathione Peroxidase (GSH-Px)", "relationship_type": "protective", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation affects ALT secretion.", "mechanism": "ALT is elevated in liver injury; beer reduces ALT, indicating hepatoprotection.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation influences AST stability.", "mechanism": "AST is increased in hepatic damage; beer lowers AST, protecting liver function.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation is essential for AKP activity.", "mechanism": "AKP is a marker of liver injury; beer reduces AKP, indicating improved liver health.", "protein": "Alkaline Phosphatase (AKP)", "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation modulates LDL receptor interactions.", "mechanism": "LDL is elevated in dyslipidemia and aging; beer lowers LDL, improving lipid profiles.", "protein": "Low Density Lipoprotein (LDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12339418" }, { "confidence": "high", "disease": "Plastic bronchitis", "glycan_involvement": "CD4 is a glycoprotein; glycosylation affects stability and T-cell signaling.", "mechanism": "Reduced CD4+/CD8+ ratio indicates immune dysregulation, associated with increased PB risk in MPP.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "high", "disease": "Plastic bronchitis", "glycan_involvement": "CD8 is a glycoprotein; glycosylation modulates T-cell receptor interactions.", "mechanism": "Increased CD8+ T-cell proportion (lower CD4+/CD8+ ratio) linked to persistent inflammation and PB.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "high", "disease": "Plastic bronchitis", "glycan_involvement": "D-dimer is a glycosylated fibrin fragment; glycosylation may affect clearance.", "mechanism": "Elevated D-dimer reflects hypercoagulability and fibrin deposition, promoting bronchial cast formation.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "Plastic bronchitis", "glycan_involvement": "IL-6 is glycosylated, which influences secretion and receptor binding.", "mechanism": "Elevated IL-6 indicates heightened inflammation, contributing to airway obstruction and cast formation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "Plastic bronchitis", "glycan_involvement": "LDH is minimally glycosylated; glycosylation has minor impact on function.", "mechanism": "Elevated LDH reflects tissue injury and cell death in PB.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "low", "disease": "Plastic bronchitis", "glycan_involvement": "Ferritin is glycosylated; glycosylation affects serum stability.", "mechanism": "Lower ferritin levels observed in PB group; may reflect altered iron metabolism in inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "low", "disease": "Plastic bronchitis", "glycan_involvement": "CRP is glycosylated, which modulates its immune effector functions.", "mechanism": "Elevated CRP indicates systemic inflammation, associated with PB risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "Glycosylation modulates CD4 stability and T-cell activation.", "mechanism": "Altered CD4+/CD8+ ratio reflects immune response severity in MPP.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "Glycosylation affects CD8 receptor function.", "mechanism": "Increased CD8+ T cells contribute to Th1-driven inflammation in severe MPP.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "Mycoplasma pneumoniae pneumonia (MPP)", "glycan_involvement": "Glycosylation affects IL-6 secretion and activity.", "mechanism": "Elevated IL-6 is a marker of severe inflammation in MPP.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339448" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation affects apolipoprotein stability and lipid transport.", "mechanism": "Altered apolipoprotein levels reflect dysregulated lipid metabolism in MAFLD.", "protein": "Apolipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Glycosylation may affect ALT secretion and stability.", "mechanism": "Elevated ALT indicates hepatocyte injury in MAFLD.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Glycosylation modulates \u03b3-GT activity and localization.", "mechanism": "Increased \u03b3-GT reflects oxidative stress and liver dysfunction in MAFLD.", "protein": "\u03b3-GT (Gamma-glutamyl transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation influences HDL particle composition and function.", "mechanism": "Low HDL-C is associated with metabolic dysfunction in MAFLD.", "protein": "HDL-C (High-density lipoprotein cholesterol)", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation may regulate AST secretion.", "mechanism": "Elevated AST is indicative of liver cell damage in MAFLD.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation alters apolipoprotein function in lipid transport.", "mechanism": "Apolipoprotein levels are linked to cardiovascular risk in MAFLD patients.", "protein": "Apolipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation may affect ALT half-life.", "mechanism": "ALT elevation correlates with progression to hepatic fibrosis in MAFLD.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates \u03b3-GT enzymatic activity.", "mechanism": "\u03b3-GT elevation is associated with increased diabetes risk in MAFLD.", "protein": "\u03b3-GT (Gamma-glutamyl transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects HDL function and anti-inflammatory properties.", "mechanism": "Low HDL-C increases cardiovascular risk in MAFLD.", "protein": "HDL-C (High-density lipoprotein cholesterol)", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation impacts apolipoprotein-mediated glucose metabolism.", "mechanism": "Apolipoprotein dysregulation is linked to diabetes in MAFLD context.", "protein": "Apolipoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12339455" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "NLRP3 is a glycoprotein; glycosylation may affect its stability and activation (not directly studied here).", "mechanism": "NLRP3 inflammasome activation triggers caspase-1 and pyroptosis, leading to liver inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 release is a hallmark of pyroptosis and correlates with liver inflammation severity.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "IL-18 is glycosylated; glycosylation modulates cytokine function.", "mechanism": "IL-18 is released during pyroptosis and contributes to inflammatory response in liver injury.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Pyroptosis-associated inflammation", "glycan_involvement": "Glycosylation may regulate NLRP3 function.", "mechanism": "NLRP3 activation leads to pyroptosis in macrophages, driving inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12339467" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not directly addressed.", "mechanism": "Macrophage pyroptosis via NLRP3 contributes to atherosclerotic lesion formation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12339467" }, { "confidence": "medium", "disease": "Lung inflammation", "glycan_involvement": "Not directly addressed.", "mechanism": "Silica-induced macrophage pyroptosis via NLRP3 leads to lung inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12339467" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Not directly addressed.", "mechanism": "GAS5/miR-223/NLRP3 axis implicated in neuroinflammation via pyroptosis.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "Potential modulation of glycoprotein function by PAMK.", "mechanism": "PAMK suppresses NLRP3 activation, reducing pyroptosis and liver inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "Glycosylation affects cytokine secretion; PAMK may influence this.", "mechanism": "PAMK reduces IL-1\u03b2 release, alleviating liver inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Inflammatory liver injury", "glycan_involvement": "Glycosylation affects cytokine secretion; PAMK may influence this.", "mechanism": "PAMK reduces IL-18 release, mitigating liver inflammation.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339467" }, { "confidence": "high", "disease": "Graft-versus-host disease (GvHD)", "glycan_involvement": "CD2 is a glycoprotein; glycosylation may affect antibody binding and targeting.", "mechanism": "CD2-targeted nanoparticles induce tolerogenic NK cells and Tregs, protecting against GvHD.", "protein": "CD2", "protein_enriched": { "function": "CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytop", "gene_name": "CD2", "glycan_count": 20, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G37399XV", "G53075ES", "G49108TO", "G83161QT", "G05724UK", "G06110VR", "G23863VK", "G31544HA", "G39188ZX", "G55220VL", "G63889NK", "G64527OM", "G72797UR", "G77149EE", "G78059CC", "G80966KZ", "G86357DX", "G87618BG", "G90093AU", "G93993PD" ], "uniprot_id": "P06729" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339487" }, { "confidence": "high", "disease": "Graft-versus-host disease (GvHD)", "glycan_involvement": "GARP is a glycoprotein; glycosylation may regulate surface expression and TGF-\u03b2 presentation.", "mechanism": "GARP on NK cells binds latent TGF-\u03b2, facilitating its activation and Treg maintenance.", "protein": "GARP (LRRC32)", "relationship_type": "protective", "source_pmcid": "PMC12339487" }, { "confidence": "high", "disease": "Graft-versus-host disease (GvHD)", "glycan_involvement": "TGF-\u03b21 is secreted as a latent complex with glycosylated LAP; glycosylation regulates activation.", "mechanism": "NK cell-derived TGF-\u03b21 stabilizes Tregs, preventing GvHD.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "protective", "source_pmcid": "PMC12339487" }, { "confidence": "medium", "disease": "Graft-versus-host disease (GvHD)", "glycan_involvement": "CD56 is highly glycosylated; glycosylation affects NK cell interactions.", "mechanism": "CD56bright NK cells produce TGF-\u03b2, supporting Treg stability and immune tolerance.", "protein": "CD56 (NCAM1)", "relationship_type": "protective", "source_pmcid": "PMC12339487" }, { "confidence": "high", "disease": "Graft-versus-host disease (GvHD)", "glycan_involvement": "IL-2 is glycosylated; glycosylation may affect stability and receptor binding.", "mechanism": "IL-2 from nanoparticles induces Tregs, but requires TGF-\u03b2 for tolerogenic effect.", "protein": "IL-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339487" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "FOXP3 stability is regulated by TSDR methylation, not direct glycosylation.", "mechanism": "FOXP3+ Tregs are reduced/unstable in SLE due to deficient IL-2/TGF-\u03b2 signaling.", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339487" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CD25 is glycosylated; glycosylation may affect receptor function.", "mechanism": "IL-2 muteins targeting CD25 failed in SLE due to lack of NK cell (IL-2R\u03b2) engagement.", "protein": "CD25 (IL-2R\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339487" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Latent TGF-\u03b2 complex glycosylation affects activation.", "mechanism": "Deficient TGF-\u03b21 production in SLE leads to Treg instability and disease progression.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12339487" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "CD8 is a glycoprotein; glycosylation may affect Treg function.", "mechanism": "CD8+ Tregs induced by IL-2/TGF-\u03b2 protect against type 1 diabetes.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "protective", "source_pmcid": "PMC12339487" }, { "confidence": "medium", "disease": "Pregnancy complications (maternal/fetal tolerance)", "glycan_involvement": "Glycosylation of CD56 modulates NK cell function at maternal/fetal interface.", "mechanism": "CD56bright NK cells produce TGF-\u03b2, supporting decidual Tregs and fetal tolerance.", "protein": "CD56 (NCAM1)", "relationship_type": "protective", "source_pmcid": "PMC12339487" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Nephrin is N-glycosylated, essential for its cell surface localization and function.", "mechanism": "Sweroside upregulates nephrin expression, stabilizing the glomerular filtration barrier and improving podocyte function.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "protective", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Podocin is a membrane glycoprotein; glycosylation may affect stability.", "mechanism": "Sweroside increases podocin expression, supporting podocyte integrity.", "protein": "Podocin", "protein_enriched": { "function": "Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton", "gene_name": "NPHS2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP85" }, "relationship_type": "protective", "source_pmcid": "PMC12339515" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Sweroside downregulates desmin, a marker of podocyte injury.", "protein": "Desmin", "protein_enriched": { "function": "Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and f", "gene_name": "DES", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G18647XP", "G37399XV", "G41247ZX", "G47644PP", "G63041LO", "G84349RE", "G90575OW", "G49108TO" ], "uniprot_id": "P17661" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339515" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "O-glycosylation modulates HIF1\u03b1 stability.", "mechanism": "Sweroside downregulates HIF1\u03b1, reducing hypoxia-induced damage.", "protein": "HIF1\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "O-glycosylation regulates RUNX2 activity.", "mechanism": "Sweroside upregulates RUNX2, promoting osteoblast differentiation.", "protein": "RUNX2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Osteocalcin is a secreted glycoprotein; glycosylation affects secretion.", "mechanism": "Sweroside increases osteocalcin secretion, enhancing bone formation.", "protein": "Osteocalcin (BGLAP)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation is important for collagen stability.", "mechanism": "Sweroside upregulates COL1A1, supporting bone matrix formation.", "protein": "COL1A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "OPG is a glycoprotein; glycosylation is critical for function.", "mechanism": "Sweroside upregulates OPG, inhibiting osteoclastogenesis.", "protein": "OPG (TNFRSF11B)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "RANKL is glycosylated; glycosylation affects receptor binding.", "mechanism": "Sweroside downregulates RANKL, reducing bone resorption.", "protein": "RANKL (TNFSF11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339515" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects osteocalcin secretion.", "mechanism": "Sweroside increases osteocalcin, indicating improved bone turnover in inflammatory arthritis.", "protein": "Osteocalcin (BGLAP)", "relationship_type": "biomarker", "source_pmcid": "PMC12339515" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "HLA-G is a glycoprotein; glycosylation affects its stability and immune function.", "mechanism": "Low plasma soluble HLA-G (sHLA-G) levels are associated with PBC and correlate with disease severity and poor response to ursodeoxycholic acid therapy.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "high", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation may influence HLA-G membrane expression and shedding.", "mechanism": "HLA-G*01:01:01:08/UTR-1 haplotype is a genetic risk factor for PBC, associated with lower sHLA-G levels and increased susceptibility.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "causal", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis (PBC)", "glycan_involvement": "Glycosylation status may affect therapeutic modulation of HLA-G.", "mechanism": "Increasing HLA-G levels may improve immune tolerance and disease outcomes in PBC.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339529" }, { "confidence": "high", "disease": "Autoimmune Hepatitis Type 1 (AIH-1)", "glycan_involvement": "Glycosylation impacts HLA-G function in immune regulation.", "mechanism": "Lower sHLA-G levels are associated with increased disease severity in AIH-1.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation affects HLA-G stability and immune modulation.", "mechanism": "Low sHLA-G levels correlate with high disease activity.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates HLA-G immune functions.", "mechanism": "Lower sHLA-G levels are observed in patients with more severe disease.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation influences HLA-G\u2019s immunomodulatory role.", "mechanism": "Reduced sHLA-G levels are linked to disease activity.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Systemic Sclerosis", "glycan_involvement": "Glycosylation affects HLA-G\u2019s stability and function.", "mechanism": "Lower sHLA-G levels are associated with more severe disease.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation modulates HLA-G\u2019s immune regulatory properties.", "mechanism": "HLA-G expression is linked to liver homeostasis and injury response.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation impacts HLA-G\u2019s role in immune escape.", "mechanism": "HLA-G facilitates immune evasion and tumor progression.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12339529" }, { "confidence": "high", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "VEGF promotes tumor angiogenesis, supporting growth and metastasis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "high", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation affects receptor stability and ligand binding.", "mechanism": "VEGFR-2 mediates angiogenic signaling; inhibition suppresses tumor vascularization.", "protein": "VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "high", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation modulates surface expression and ligand interaction.", "mechanism": "PD-1 inhibits T cell activation; blockade enhances anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "high", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 expression correlates with response to immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "medium", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "VEGFR-1 regulates vascular maturation; inhibition may impact tumor microenvironment.", "protein": "VEGFR-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "medium", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation influences receptor trafficking.", "mechanism": "VEGFR-3 drives lymphangiogenesis and metastatic spread.", "protein": "VEGFR-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "medium", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation critical for peptide loading and stability.", "mechanism": "MHC I presentation is essential for immune recognition; altered glycosylation may affect antigen presentation.", "protein": "MHC I", "relationship_type": "biomarker", "source_pmcid": "PMC12339537" }, { "confidence": "medium", "disease": "MSI-H Gastric Cancer", "glycan_involvement": "Defective glycosylation due to mismatch repair deficiency.", "mechanism": "MSI-H status predicts better response to immunotherapy.", "protein": "MSI-H related glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12339537" }, { "confidence": "medium", "disease": "EBV-associated Gastric Cancer", "glycan_involvement": "Viral glycoproteins are highly glycosylated, affecting immune evasion.", "mechanism": "EBV glycoproteins contribute to oncogenesis and immune modulation.", "protein": "EBV encoded glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12339537" }, { "confidence": "low", "disease": "Gastric Adenocarcinoma", "glycan_involvement": "N-glycosylation required for ligand binding and dimerization.", "mechanism": "EGFR signaling promotes proliferation; glycosylation modulates receptor activity.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339537" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B promotes adipogenesis and lipid accumulation; inhibition reduces adipocyte differentiation and fat mass.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12339561" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B dysregulation increases hepatic gluconeogenesis and insulin resistance; inhibition improves glucose tolerance and insulin sensitivity.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12339561" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B promotes hepatic lipid accumulation and inflammation; inhibition reduces liver fat and inflammatory markers.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12339561" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Gain-of-function mutations in DYRK1B are linked to familial metabolic syndrome.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Perilipin is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Perilipin is essential for lipid droplet formation; its expression is regulated by DYRK1B during adipogenesis.", "protein": "Perilipin", "relationship_type": "causal", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Adiponectin is a glycoprotein; glycosylation is critical for secretion and function.", "mechanism": "Adiponectin is decreased during adipogenesis; KS-40070 reduces adiponectin expression, reflecting reduced adipocyte differentiation.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "TNF\u03b1 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "TNF\u03b1 promotes hepatic inflammation and fibrosis; KS-40070 reduces TNF\u03b1 expression in liver.", "protein": "TNF\u03b1", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B mutations are associated with increased risk of coronary artery disease.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B mutations are associated with hypertension in metabolic syndrome.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339561" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "DYRK1B expression increases during adipogenesis; potential biomarker for adipocyte differentiation.", "protein": "DYRK1B", "protein_enriched": { "function": "Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenanc", "gene_name": "DYRK1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y463" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339561" }, { "confidence": "high", "disease": "Acute kidney injury", "glycan_involvement": "KIM1 is a heavily glycosylated protein; glycosylation is essential for its stability and function as a biomarker.", "mechanism": "KIM1 is upregulated in kidney tissue in response to injury.", "protein": "KIM1 (Kidney Injury Molecule-1)", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "Slamf7", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8BHK6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Fgf21 is glycosylated, which affects its secretion and activity.", "mechanism": "Regulated by adipose-derived miRNAs; involved in metabolic adaptation during liver injury.", "protein": "Fgf21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity probably requires the presence of KL", "gene_name": "Fgf21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9JJN1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation modulates RNA binding and vesicle targeting.", "mechanism": "Mediates selective packaging of mRNAs into extracellular vesicles, potentially influencing kidney pathology.", "protein": "HNRNPA2B1", "protein_enriched": { "function": "Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-", "gene_name": "HNRNPA2B1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P22626" }, "relationship_type": "causal", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "TBG is N-glycosylated, which is critical for its serum half-life.", "mechanism": "TBG promoter used for hepatocyte-specific expression; TBG levels can reflect liver synthetic function.", "protein": "TBG (Thyroxine Binding Globulin)", "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Kidney disease", "glycan_involvement": "Clusterin is highly glycosylated, affecting its chaperone activity and stability.", "mechanism": "Clusterin is upregulated in kidney injury and present in extracellular vesicles.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Podocin is glycosylated; glycosylation is important for membrane localization.", "mechanism": "Podocin mutations/glycosylation defects disrupt glomerular filtration, leading to proteinuria.", "protein": "Podocin", "protein_enriched": { "function": "Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton", "gene_name": "NPHS2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP85" }, "relationship_type": "causal", "source_pmcid": "PMC12339719" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation is required for KIM1's detection in urine and plasma.", "mechanism": "KIM1 is persistently upregulated in chronic injury.", "protein": "KIM1 (Kidney Injury Molecule-1)", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "Slamf7", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8BHK6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation modulates its anti-apoptotic and chaperone functions.", "mechanism": "Clusterin is associated with tissue remodeling and fibrosis.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "low", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects its RNA-binding and vesicle sorting.", "mechanism": "Regulates exRNA content in vesicles during inflammation.", "protein": "HNRNPA2B1", "protein_enriched": { "function": "Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-", "gene_name": "HNRNPA2B1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P22626" }, "relationship_type": "causal", "source_pmcid": "PMC12339719" }, { "confidence": "medium", "disease": "Pre-renal injury", "glycan_involvement": "Glycosylation is necessary for KIM1's function as a cell-surface receptor.", "mechanism": "KIM1 is upregulated in response to pre-renal stress.", "protein": "KIM1 (Kidney Injury Molecule-1)", "protein_enriched": { "function": "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and different", "gene_name": "Slamf7", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q8BHK6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339719" }, { "confidence": "high", "disease": "Aging/Immunosenescence", "glycan_involvement": "CD5 is a glycoprotein; altered expression affects glycosylated surface CD5 levels.", "mechanism": "IL-10-driven exon switch (E1A\u2192E1B) reduces surface CD5 (sCD5) expression on T cells, impairing immune response and promoting immunosenescence.", "protein": "CD5", "relationship_type": "causal", "source_pmcid": "PMC12339811" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Loss of glycosylated sCD5 may alter immune regulation.", "mechanism": "Reduced sCD5 expression is associated with SLE pathogenesis.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12339811" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Altered glycosylation state of CD5 may affect T-cell function.", "mechanism": "Reduced sCD5 expression is linked to MS.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12339811" }, { "confidence": "medium", "disease": "B-cell Chronic Lymphocytic Leukemia", "glycan_involvement": "CD5 glycosylation status may influence leukemic cell phenotype.", "mechanism": "Reduced sCD5 expression is observed in B-CLL.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12339811" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL)", "glycan_involvement": "Loss of glycosylated sCD5 on T cells is a feature of T-ALL.", "mechanism": "E1A\u2192E1B exon switch leads to CD5 low/neg phenotype, contributing to leukemic transformation.", "protein": "CD5", "relationship_type": "causal", "source_pmcid": "PMC12339811" }, { "confidence": "medium", "disease": "Chronic Inflammatory Diseases", "glycan_involvement": "Modulation of glycosylated CD5 may impact immune cell signaling.", "mechanism": "IL-10/CEBP-\u03b2 pathway modulates CD5 expression; targeting this axis may modulate inflammation.", "protein": "CD5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339811" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CD5 glycosylation may affect tumor immune evasion.", "mechanism": "Altered CD5 expression via IL-10/CEBP-\u03b2 axis may be targeted for cancer immunotherapy.", "protein": "CD5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339811" }, { "confidence": "high", "disease": "Aging/Immunosenescence", "glycan_involvement": "Decrease in glycosylated sCD5 reflects immune aging.", "mechanism": "Reduced sCD5 is a marker of T-cell aging and immune dysfunction.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12339811" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL)", "glycan_involvement": "Loss of glycosylated sCD5 on T cells.", "mechanism": "CD5 low/neg phenotype (due to E1B upregulation) is a feature of leukemic T cells.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12339811" }, { "confidence": "high", "disease": "Immunosenescence/Inflammaging", "glycan_involvement": "Reduced glycosylated sCD5 alters T-cell signaling and inflammation.", "mechanism": "IL-10-induced CEBP-\u03b2/LIP upregulation drives E1A\u2192E1B switch, reducing sCD5 and promoting chronic inflammation.", "protein": "CD5", "relationship_type": "causal", "source_pmcid": "PMC12339811" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation modulates EGFR stability and ligand binding.", "mechanism": "EGFR promotes immune evasion and tumor progression; knockout sensitizes cells to CTL-mediated killing.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "MFGE8 is a secreted glycoprotein; glycosylation affects secretion and function.", "mechanism": "MFGE8 promotes immune evasion; knockout increases susceptibility to CTL-mediated cytotoxicity.", "protein": "MFGE8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339858" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Proteasome subunits can be glycosylated, affecting assembly/function.", "mechanism": "PSMA6 is essential for PDAC cell survival; knockout induces apoptosis.", "protein": "PSMA6", "protein_enriched": { "function": "Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with dif", "gene_name": "PSMA6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Chemoresistance in pancreatic cancer", "glycan_involvement": "N-glycosylation required for ABCG2 trafficking and drug efflux activity.", "mechanism": "ABCG2 upregulation confers multidrug resistance.", "protein": "ABCG2", "relationship_type": "causal", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "No direct glycosylation, but KRAS signaling regulates glycoprotein expression.", "mechanism": "Mutant KRAS drives tumorigenesis and progression.", "protein": "KRAS", "relationship_type": "causal", "source_pmcid": "PMC12339858" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Potential glycosylation may affect stability.", "mechanism": "USP15 acts as a tumor suppressor; loss increases proliferation and reduces survival.", "protein": "USP15", "relationship_type": "protective", "source_pmcid": "PMC12339858" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Potential glycosylation may affect function.", "mechanism": "SCAF1 acts as a tumor suppressor; loss increases proliferation.", "protein": "SCAF1", "protein_enriched": { "function": "Nucleolar protein that is involved in ribosomal RNA (rRNA) processing (PubMed:33199730). Also plays a role in primary cilia resorption, and cell cycle progression in neurogenesis and neocortex develop", "gene_name": "RRP7A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3A4" }, "relationship_type": "protective", "source_pmcid": "PMC12339858" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Potential glycosylation may affect chromatin remodeling.", "mechanism": "ARID1A loss increases sensitivity to dasatinib and VE-821.", "protein": "ARID1A", "protein_enriched": { "function": "Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry ou", "gene_name": "ARID1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O14497" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Immune evasion in pancreatic cancer", "glycan_involvement": "Glycosylation required for secretion and immune modulation.", "mechanism": "MFGE8 expression promotes immune escape from CD8+ T cells.", "protein": "MFGE8", "relationship_type": "causal", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Chemoresistance in pancreatic cancer", "glycan_involvement": "N-glycosylation modulates EGFR function and drug response.", "mechanism": "EGFR expression correlates with poor prognosis and immune evasion.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339858" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "No direct glycosylation; bacterial protein.", "mechanism": "ClpC1 is essential for Mtb viability; targeted by cyclomarins, rufomycins, ilamycins.", "protein": "Caseinolytic protease C1 (ClpC1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339860" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation critical for cell wall integrity and host interaction.", "mechanism": "Cell wall glycoproteins contribute to immune evasion and pathogenicity.", "protein": "Mycobacterium tuberculosis cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12339860" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation of mycolic acids modulates cell wall properties.", "mechanism": "Mycolic acid glycoproteins confer acid-fastness and drug resistance.", "protein": "Mycolic acid-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12339860" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation enhances immunogenicity.", "mechanism": "BCG glycoproteins induce trained immunity and protection.", "protein": "BCG vaccine glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12339860" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "No direct glycosylation; possible indirect effects on glycoprotein expression.", "mechanism": "Rifamycins inhibit bacterial RNA polymerase.", "protein": "Rifamycin-binding proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339860" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "No direct glycosylation.", "mechanism": "Aminoglycosides bind ribosomal proteins, inhibiting protein synthesis.", "protein": "Aminoglycoside-binding ribosomal proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339860" }, { "confidence": "high", "disease": "Multidrug-resistant tuberculosis (MDR-TB)", "glycan_involvement": "No direct glycosylation.", "mechanism": "Tuberactinomycins bind 30S/50S ribosomal subunits, effective against MDR/XDR strains.", "protein": "Tuberactinomycin-binding ribosomal proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339860" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation modulates immune cell function.", "mechanism": "Host glycoproteins mediate immune recognition and granuloma formation.", "protein": "Host immune cell glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12339860" }, { "confidence": "low", "disease": "Latent tuberculosis", "glycan_involvement": "Altered glycosylation patterns in granuloma matrix.", "mechanism": "Glycoproteins in granulomas may indicate latent infection.", "protein": "Granuloma-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12339860" }, { "confidence": "medium", "disease": "Antimicrobial resistance", "glycan_involvement": "Glycosylation increases cell wall impermeability.", "mechanism": "Cell wall glycoproteins contribute to poor drug penetration and resistance.", "protein": "Mycobacterium tuberculosis cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12339860" }, { "confidence": "high", "disease": "HIV-associated extrapyramidal motor dysfunction", "glycan_involvement": "Tat is not glycosylated; effect is independent of glycosylation.", "mechanism": "Extracellular Tat impairs dopaminergic neurons, reduces dopamine, and induces motor dysfunction.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "Parkinson\u2019s disease-like motor abnormalities", "glycan_involvement": "Tat is not glycosylated.", "mechanism": "Tat induces neuronal apoptosis, oxidative stress, and inhibits tyrosine hydroxylase in dopaminergic pathways.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC12339940" }, { "confidence": "medium", "disease": "HIV-associated extrapyramidal motor dysfunction", "glycan_involvement": "Tat is not glycosylated; antibody response not glycan-dependent.", "mechanism": "Higher anti-Tat IgG (especially against cysteine-rich region) is associated with less severe motor dysfunction.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "protective", "source_pmcid": "PMC12339940" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive impairment", "glycan_involvement": "Tat is not glycosylated.", "mechanism": "Anti-Tat antibody levels do not correlate with neurocognitive impairment severity.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "correlative", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "gp120 is heavily N-glycosylated; glycans shield epitopes and affect immunogenicity.", "mechanism": "Robust anti-gp120 IgG responses are elicited during HIV infection.", "protein": "gp120", "relationship_type": "biomarker", "source_pmcid": "PMC12339940" }, { "confidence": "medium", "disease": "HIV-associated neurocognitive impairment", "glycan_involvement": "N-glycans modulate neurotoxicity and immune evasion.", "mechanism": "gp120 contributes to glutamate excitotoxicity and neuronal toxicity.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Tat is not glycosylated.", "mechanism": "Tat persists in blood and CSF of ART-treated PWH, indicating ongoing viral activity.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339940" }, { "confidence": "medium", "disease": "HIV-associated extrapyramidal motor dysfunction", "glycan_involvement": "Tat is not glycosylated.", "mechanism": "Tat vaccination elicits neutralizing antibodies in animals, suggesting potential to alleviate motor dysfunction.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Nef is not glycosylated.", "mechanism": "Anti-Nef IgG responses are robust in HIV infection.", "protein": "Nef", "protein_enriched": { "function": "Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host ", "gene_name": "nef", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03407" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "p24 is not glycosylated.", "mechanism": "Anti-p24 IgG responses are robust in HIV infection.", "protein": "p24", "relationship_type": "biomarker", "source_pmcid": "PMC12339940" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Lp(a) contains heavily glycosylated apolipoprotein(a), which affects its plasma levels and function.", "mechanism": "Lp(a) promotes atherosclerosis, calcification, and thrombosis; high plasma levels are independently associated with increased CAD risk.", "protein": "Lipoprotein (a) (Lp(a))", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339960" }, { "confidence": "high", "disease": "Atherosclerotic cardiovascular disease (ASCVD)", "glycan_involvement": "Glycosylation of apo(a) modulates Lp(a) plasma concentration and pathogenicity.", "mechanism": "Elevated Lp(a) is associated with increased risk of ASCVD via pro-atherogenic and pro-thrombotic effects.", "protein": "Lipoprotein (a) (Lp(a))", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339960" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "ALP is a glycoprotein; glycosylation is important for its stability and secretion.", "mechanism": "ALP promotes vascular calcification by hydrolyzing inorganic pyrophosphate, an inhibitor of calcification; high ALP is independently associated with CAD risk.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12339960" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation affects ALP's enzymatic activity and half-life.", "mechanism": "ALP degrades inorganic pyrophosphate, reducing its protective effect and promoting vascular calcification.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "causal", "source_pmcid": "PMC12339960" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "ApoB is N-glycosylated, which influences lipoprotein assembly and clearance.", "mechanism": "ApoB is a structural component of atherogenic lipoproteins; elevated levels are associated with increased CAD risk.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12339960" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "ApoA1 glycosylation may affect HDL function and anti-atherogenic properties.", "mechanism": "ApoA1 is the main protein in HDL; higher levels are generally protective against CAD.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12339960" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation of apo(a) tail influences Lp(a) structure and vascular interactions.", "mechanism": "Lp(a) promotes vascular calcification through its pro-inflammatory and pro-calcific effects.", "protein": "Lipoprotein (a) (Lp(a))", "relationship_type": "causal", "source_pmcid": "PMC12339960" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "SREBP1 is a glycoprotein; glycosylation may affect its stability and nuclear translocation.", "mechanism": "SREBP1 upregulation promotes hepatic lipogenesis and steatosis; inhibition reduces NAFLD severity.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339966" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "FASN is N-glycosylated, which may influence its enzymatic activity and stability.", "mechanism": "FASN is upregulated in NAFLD, driving fatty acid synthesis and lipid accumulation; inhibition ameliorates NAFLD.", "protein": "FASN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12339966" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "AMPK is a glycoprotein; glycosylation may modulate its activity.", "mechanism": "AMPK activation inhibits SREBP1 and FASN, reducing hepatic lipogenesis and improving NAFLD.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "Glycosylation may regulate SREBP1 function in disease progression.", "mechanism": "SREBP1-driven lipogenesis contributes to progression from NAFLD to NASH.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "causal", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation may affect FASN's catalytic efficiency.", "mechanism": "FASN-mediated fatty acid synthesis leads to lipid droplet accumulation in hepatocytes.", "protein": "FASN", "relationship_type": "causal", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may influence AMPK's cellular localization and function.", "mechanism": "AMPK activation improves insulin sensitivity by modulating lipid metabolism.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated, which can affect secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 reflects hepatic inflammation in NAFLD/NASH.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "IL-1\u03b2 glycosylation may modulate its bioactivity.", "mechanism": "Increased IL-1\u03b2 is associated with inflammatory progression in NAFLD.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "IL-6 glycosylation affects its stability and receptor interaction.", "mechanism": "IL-6 elevation indicates ongoing hepatic inflammation in NAFLD.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may regulate SREBP1's transcriptional activity.", "mechanism": "SREBP1-induced lipogenesis exacerbates insulin resistance in NAFLD.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "causal", "source_pmcid": "PMC12339966" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Not directly specified; as a putative glycoprotein, glycosylation may affect stability or signaling.", "mechanism": "Regulates Wnt/\u03b2-catenin and TNF-\u03b1/NF-\u03baB signaling, influencing osteoblast/osteoclast balance and inflammation.", "protein": "CPNE1", "protein_enriched": { "function": "Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes (PubMed:14674885). Involved in the TNF-alpha receptor signaling pathway in a calcium-depend", "gene_name": "CPNE1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99829" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Not directly specified.", "mechanism": "Associated with immune cell infiltration (Tregs, monocytes); may exacerbate \u03b2-cell damage via inflammation.", "protein": "CPNE1", "protein_enriched": { "function": "Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes (PubMed:14674885). Involved in the TNF-alpha receptor signaling pathway in a calcium-depend", "gene_name": "CPNE1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99829" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Not directly specified.", "mechanism": "Activates Wnt/\u03b2-catenin signaling by inhibiting GSK-3\u03b2, promoting bone formation and regulating osteoclastogenesis.", "protein": "FRAT2", "protein_enriched": { "function": "Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into", "gene_name": "CHMP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3E7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Not directly specified.", "mechanism": "Linked to immune infiltration (monocytes); may contribute to \u03b2-cell dysfunction via inflammatory pathways.", "protein": "FRAT2", "protein_enriched": { "function": "Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into", "gene_name": "CHMP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y3E7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12340000" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Secreted glycoprotein antagonist of Wnt signaling; upregulation blocks LRP5/6, accelerating bone loss.", "protein": "DKK1", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:220", "gene_name": "DKK1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "O94907" }, "relationship_type": "causal", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates stability and function.", "mechanism": "Elevated in T1DM; contributes to bone loss by inhibiting Wnt/\u03b2-catenin signaling.", "protein": "DKK1", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:220", "gene_name": "DKK1", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "O94907" }, "relationship_type": "causal", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation essential for secretion and receptor binding.", "mechanism": "Promotes osteoblast differentiation via Wnt signaling; downregulation linked to bone loss.", "protein": "WNT10B", "protein_enriched": { "function": "Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-ca", "gene_name": "WNT10B", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O00744" }, "relationship_type": "protective", "source_pmcid": "PMC12340000" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "Involved in bone matrix regulation; altered expression associated with bone fragility.", "protein": "SERPINF1", "relationship_type": "biomarker", "source_pmcid": "PMC12340000" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates cell-cell interaction.", "mechanism": "Cell adhesion glycoprotein; may influence osteoclast/osteoblast interactions.", "protein": "ALCAM", "relationship_type": "biomarker", "source_pmcid": "PMC12340000" }, { "confidence": "low", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Integrin involved in osteoclast function; altered expression may affect bone resorption.", "protein": "ITGB3", "relationship_type": "biomarker", "source_pmcid": "PMC12340000" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "Glycosylation required for proper trafficking and function.", "mechanism": "Mediates renal urate reabsorption; inhibition lowers serum uric acid and prevents gout flares.", "protein": "URAT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "N-glycosylation affects membrane localization and stability.", "mechanism": "Major urate reabsorption transporter; inhibition promotes uric acid excretion.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340016" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "Glycosylation modulates transporter function.", "mechanism": "Contributes to renal urate reabsorption; inhibition increases uric acid excretion.", "protein": "OAT4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "Glycosylation may regulate inflammasome assembly (not directly shown in this article).", "mechanism": "Inflammasome activation by MSU crystals triggers IL-1\u03b2 release and joint inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Acute gouty arthritis", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Key cytokine released upon NLRP3 activation; drives acute joint inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation essential for transporter function.", "mechanism": "Overactivity leads to decreased uric acid excretion and elevated serum uric acid.", "protein": "URAT1", "relationship_type": "causal", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "N-glycosylation affects function.", "mechanism": "Facilitates urate reabsorption; increased activity raises serum uric acid.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "causal", "source_pmcid": "PMC12340016" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Possible, but not detailed in this article.", "mechanism": "Chronic activation contributes to renal inflammation and damage.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12340016" }, { "confidence": "medium", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation modulates function.", "mechanism": "Promotes urate reabsorption; dysfunction or inhibition affects uric acid levels.", "protein": "OAT4", "relationship_type": "causal", "source_pmcid": "PMC12340016" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Not specified.", "mechanism": "Inflammasome activation implicated in systemic inflammation of metabolic syndrome.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12340016" }, { "confidence": "high", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "O-mannosylation required for dystrophin-associated glycoprotein complex stability.", "mechanism": "Loss of dystrophin disrupts linkage between cytoskeleton and ECM, causing muscle degeneration.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC12340039" }, { "confidence": "high", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation critical for collagen secretion and ECM assembly.", "mechanism": "Downregulation reflects impaired ECM integrity and increased fibrosis in DMD muscle.", "protein": "Collagen VI alpha-1 (Col6a1)", "protein_enriched": { "function": "May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulati", "gene_name": "CTNNA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P26232" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation modulates Mmp2 secretion and activity.", "mechanism": "Downregulation reduces ECM turnover, promoting fibrosis.", "protein": "Matrix metalloproteinase-2 (Mmp2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation required for ECM interactions.", "mechanism": "Reduced expression impairs ECM remodeling and muscle regeneration.", "protein": "Fibronectin (Fn1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Binds \u03b2-galactoside glycans on cell surface glycoproteins.", "mechanism": "Downregulation impairs immune cell recruitment and resolution of inflammation.", "protein": "Galectin-3 (Lgals3)", "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N- and O-glycans modulate ligand binding and cell trafficking.", "mechanism": "Downregulation reduces immune cell adhesion and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "Downregulation alters fibrosis and muscle regeneration balance.", "protein": "Transforming growth factor beta-1 (Tgf\u03b21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340039" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "N-glycosylation modulates ligand binding and signaling.", "mechanism": "Altered integrin signaling impairs muscle-ECM adhesion.", "protein": "Integrin beta-1 (Itgb1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340039" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential O-glycosylation may affect actin interactions.", "mechanism": "Downregulation reflects impaired muscle contraction.", "protein": "Actin alpha cardiac muscle 1 (Actc1)", "protein_enriched": { "function": "Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells", "gene_name": "Actc1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P68033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "low", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Potential O-glycosylation may modulate function.", "mechanism": "Downregulation indicates impaired muscle regeneration.", "protein": "Myosin heavy chain 3 (Myh3)", "protein_enriched": { "function": "Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents", "gene_name": "Tff1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q63467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340039" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Fam222B is a putative glycoprotein; glycosylation may affect its function or localization, but not directly studied.", "mechanism": "Fam222B is required for delphinidin-induced upregulation of let-7b, leading to inhibition of melanoma cell proliferation.", "protein": "Fam222B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340061" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "No direct glycosylation involvement reported for cyclin D1 in this study.", "mechanism": "Delphinidin suppresses cyclin D1 protein levels via let-7b upregulation, resulting in cell cycle arrest.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340061" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "miRNA function may be modulated by glycoprotein complexes, but not directly addressed.", "mechanism": "let-7b inhibits melanoma cell proliferation by targeting cyclin D1; upregulated by delphinidin via Fam222B.", "protein": "let-7b (miRNA)", "relationship_type": "protective", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Muscle Atrophy", "glycan_involvement": "Putative glycosylation of Fam222B may influence miRNA regulation.", "mechanism": "Fam222B regulates miR-23a expression, which is increased by delphinidin and associated with muscle protection.", "protein": "Fam222B", "relationship_type": "protective", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Indirect, via glycoprotein-mediated miRNA processing.", "mechanism": "let-7b inhibits breast cancer cell growth; delphinidin may upregulate let-7b.", "protein": "let-7b (miRNA)", "relationship_type": "protective", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "Indirect, via glycoprotein-mediated miRNA processing.", "mechanism": "let-7b inhibits lung cancer cell growth; upregulated by delphinidin.", "protein": "let-7b (miRNA)", "relationship_type": "protective", "source_pmcid": "PMC12340061" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Putative glycosylation may affect Fam222B's regulatory function.", "mechanism": "Fam222B may regulate miRNAs involved in inflammatory pathways, modulated by delphinidin.", "protein": "Fam222B", "relationship_type": "protective", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation may impact Fam222B's interaction with miRNA machinery.", "mechanism": "Fam222B silencing downregulates hundreds of miRNAs involved in cancer-related pathways.", "protein": "Fam222B", "relationship_type": "causal", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Indirect, via glycoprotein complexes in miRNA processing.", "mechanism": "Reduced let-7b expression is associated with multiple cancer types; upregulation is protective.", "protein": "let-7b (miRNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12340061" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Potential glycosylation may affect detection and function.", "mechanism": "Fam222B protein is expressed in melanoma cell lines and may serve as a marker for delphinidin responsiveness.", "protein": "Fam222B", "relationship_type": "biomarker", "source_pmcid": "PMC12340061" }, { "confidence": "high", "disease": "Head and neck cancer", "glycan_involvement": "Terminal sialic acid on glycoproteins mediates cell-cell interactions and is altered in cancer.", "mechanism": "Serum N-acetylneuraminic acid is elevated and serves as a tumor marker.", "protein": "N-acetylneuraminic acid (sialic acid)", "relationship_type": "biomarker", "source_pmcid": "PMC12340066" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Targeting sialylation on glycoproteins disrupts tumor cell interactions.", "mechanism": "Sialic acid mimetics inhibit tumor growth in vivo.", "protein": "N-acetylneuraminic acid (sialic acid)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340066" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Modifies glycosylation patterns on glycoproteins, impacting cell proliferation.", "mechanism": "Intraperitoneal N-acetyl-D-glucosamine reduces tumor size, mitosis, and angiogenesis.", "protein": "N-acetyl-D-glucosamine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340066" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma", "glycan_involvement": "O-glycosylation regulates metabolic pathways essential for tumor growth.", "mechanism": "Reduced O-glycosylation disrupts glutamine metabolism, decreasing cell proliferation and tumor growth.", "protein": "O-linked \u03b2-N-acetyl glucosamine", "relationship_type": "causal", "source_pmcid": "PMC12340066" }, { "confidence": "high", "disease": "Solid tumors", "glycan_involvement": "Indirect; glutamate metabolism is linked to glycan biosynthesis and cancer cell signaling.", "mechanism": "Enriched in fecal EVs of cancer patients; distinguishes patients from controls (AUC=0.98).", "protein": "Glutamic acid", "relationship_type": "biomarker", "source_pmcid": "PMC12340066" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Indirect; phenylalanine metabolism affects glycan biosynthesis and gut dysbiosis.", "mechanism": "Phenylalanine converts to mutagenic/carcinogenic compounds in breast tissue.", "protein": "Phenylalanine", "relationship_type": "causal", "source_pmcid": "PMC12340066" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Loss of sialylation on glycoproteins is associated with tumor progression.", "mechanism": "Depleted in fecal EVs of cancer patients; may reflect altered glycosylation.", "protein": "N-acetylneuraminic acid (sialic acid)", "relationship_type": "biomarker", "source_pmcid": "PMC12340066" }, { "confidence": "medium", "disease": "Solid tumors", "glycan_involvement": "Reduced glycosylation impacts tumor cell metabolism and proliferation.", "mechanism": "Depleted in fecal EVs of cancer patients; may reflect altered glycosylation.", "protein": "N-acetyl-D-glucosamine", "relationship_type": "biomarker", "source_pmcid": "PMC12340066" }, { "confidence": "low", "disease": "Solid tumors", "glycan_involvement": "Indirect; tryptophan catabolism interacts with glycan metabolism.", "mechanism": "Depleted in fecal EVs of cancer patients; has anti-inflammatory and anti-oxidative properties.", "protein": "Indole-3-ethanol", "relationship_type": "protective", "source_pmcid": "PMC12340066" }, { "confidence": "low", "disease": "Solid tumors", "glycan_involvement": "Indirect; nucleotide metabolism is linked to glycan biosynthesis.", "mechanism": "Depleted in fecal EVs of cancer patients; may reflect altered nucleotide and glycan metabolism.", "protein": "Guanine", "relationship_type": "biomarker", "source_pmcid": "PMC12340066" }, { "confidence": "high", "disease": "Solid cancer", "glycan_involvement": "CRP is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "CRP is an acute phase reactant elevated in response to tumor-associated inflammation; higher levels predict poor prognosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "high", "disease": "Gastrointestinal malignancy", "glycan_involvement": "Glycosylation affects CRP's serum half-life and function.", "mechanism": "Elevated CRP correlates with advanced stage and higher mortality in GI cancers.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation is essential for CRP's biological activity.", "mechanism": "High CRP is associated with poor prognosis and increased mortality.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Solid cancer", "glycan_involvement": "Haptocorrin is heavily glycosylated, which affects its B12-binding and serum stability.", "mechanism": "Elevated haptocorrin increases circulating vitamin B12, reflecting tumor burden or granulocytic response.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Solid cancer", "glycan_involvement": "N-glycosylation is critical for secretion and B12 transport.", "mechanism": "High transcobalamin II levels increase serum B12, associated with neoplastic and inflammatory states.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Hematological malignancy", "glycan_involvement": "Glycosylation is required for CRP's function.", "mechanism": "CRP is elevated in hematological cancers, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Glycosylation affects haptocorrin's clearance and function.", "mechanism": "Liver damage increases haptocorrin release, raising serum B12.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Renal failure", "glycan_involvement": "Glycosylation impacts renal clearance.", "mechanism": "Decreased clearance of glycosylated haptocorrin leads to increased serum B12.", "protein": "Haptocorrin (Transcobalamin I)", "protein_enriched": { "function": "LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates t", "gene_name": "PPBP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02775" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation is necessary for CRP's stability.", "mechanism": "High CRP is associated with poor prognosis in pancreatic cancer.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "medium", "disease": "Myeloproliferative disease", "glycan_involvement": "N-glycosylation is essential for function.", "mechanism": "Increased transcobalamin II raises serum B12 in myeloproliferative disorders.", "protein": "Transcobalamin II", "protein_enriched": { "function": "Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells", "gene_name": "TCN2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340191" }, { "confidence": "high", "disease": "Allograft rejection (VCA)", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I is essential for its recognition and clearance function.", "mechanism": "Facilitates clearance of extracellular mitochondria by promoting their binding and phagocytosis by macrophages, reducing immunogenic impact and endothelial activation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340357" }, { "confidence": "medium", "disease": "Acute rejection (AR)", "glycan_involvement": "Glycosylation modulates \u03b22-glycoprotein I's interaction with mitochondria and immune cells.", "mechanism": "Reduces circulating extracellular mitochondria, thereby attenuating inflammatory cytokine induction and adhesion molecule expression.", "protein": "\u03b22-glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340357" }, { "confidence": "medium", "disease": "Chronic rejection (CR)", "glycan_involvement": "Glycosylation status may affect long-term clearance efficiency.", "mechanism": "Potentially reduces long-term inflammatory responses by clearing mtDAMPs, limiting chronic immune activation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340357" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury (IRI)", "glycan_involvement": "Glycosylation required for optimal function in DAMP clearance.", "mechanism": "Promotes removal of mitochondria-derived DAMPs, reducing post-ischemic inflammatory cascades.", "protein": "\u03b22-glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340357" }, { "confidence": "high", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation affects its stability and immune recognition.", "mechanism": "Blockade of PD-1 by inhibitors enhances T-cell activity, leading to immune-mediated liver injury.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "PD-L1 glycosylation modulates its interaction with PD-1 and immune evasion.", "mechanism": "PD-L1 inhibitor therapy disrupts immune tolerance, increasing risk of liver autoimmunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12340372" }, { "confidence": "medium", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "CTLA-4 is glycosylated, which affects its cell surface expression and function.", "mechanism": "CTLA-4 blockade (not studied here) is associated with higher IMH risk.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation of PD-1 may affect therapeutic efficacy and immune response.", "mechanism": "PD-1 inhibitors are used to treat HCC but increase risk of IMH.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "PD-L1 glycosylation influences immune checkpoint function.", "mechanism": "PD-L1 inhibitors are used in gastric cancer, with increased IMH risk.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect serum stability.", "mechanism": "ALT elevation is a diagnostic marker for IMH.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum stability.", "mechanism": "AST elevation is a diagnostic marker for IMH.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Immune-mediated hepatitis (IMH)", "glycan_involvement": "ALP is a glycoprotein; glycosylation is essential for its activity.", "mechanism": "ALP elevation is used to classify IMH type (cholestatic/mixed).", "protein": "ALP (Alkaline phosphatase)", "relationship_type": "biomarker", "source_pmcid": "PMC12340372" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation may modulate PD-1 function in cirrhotic microenvironment.", "mechanism": "PD-1 inhibitor therapy in cirrhosis increases IMH risk.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12340372" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation may affect PD-1 immune regulation in viral hepatitis.", "mechanism": "PD-1 inhibitor therapy in hepatitis B increases IMH risk.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12340372" }, { "confidence": "high", "disease": "Diabetic wound", "glycan_involvement": "Glycosylation of VEGF is required for stability and receptor binding.", "mechanism": "NMs promote M2 macrophage polarization, increasing VEGF secretion to enhance angiogenesis and wound healing.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Bone defect", "glycan_involvement": "ANG-1 glycosylation modulates secretion and activity.", "mechanism": "NMs induce M2 macrophages to secrete ANG-1, stabilizing new vessels during bone regeneration.", "protein": "ANG-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Skin defect", "glycan_involvement": "N-glycosylation affects FGF-2 receptor interaction.", "mechanism": "NMs enhance FGF-2 secretion from immune cells, promoting endothelial cell proliferation and angiogenesis.", "protein": "FGF-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Bone defect", "glycan_involvement": "Glycosylation influences PDGFB stability.", "mechanism": "M2 macrophages induced by NMs secrete PDGFB, recruiting pericytes for vessel maturation.", "protein": "PDGFB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Skin defect", "glycan_involvement": "Glycosylation required for TGF-\u03b2 secretion.", "mechanism": "NMs promote TGF-\u03b2 secretion, supporting angiogenesis and tissue repair.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Inflammatory wound", "glycan_involvement": "Glycosylation modulates IL-10 stability.", "mechanism": "NMs induce M2 macrophages to secrete IL-10, reducing inflammation and promoting angiogenesis.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "Glycosylation affects IL-4 receptor binding.", "mechanism": "NMs deliver IL-4 or induce its secretion, polarizing macrophages to M2 and enhancing angiogenesis.", "protein": "IL-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Bone defect", "glycan_involvement": "Glycosylation required for MMP-9 secretion.", "mechanism": "M1 macrophages secrete MMP-9, degrading matrix to initiate angiogenesis; NMs modulate this process.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12340402" }, { "confidence": "low", "disease": "Vascular leakage", "glycan_involvement": "N-glycosylation critical for ICAM-1 function.", "mechanism": "Upregulation of ICAM-1 by immune cells can increase vascular permeability; NMs may modulate this.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12340402" }, { "confidence": "medium", "disease": "Bone defect", "glycan_involvement": "O-glycosylation modulates OPN activity.", "mechanism": "mDCs secrete OPN upon NM stimulation, promoting angiogenesis and bone regeneration.", "protein": "OPN (Osteopontin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340402" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation is essential for VEGF secretion and receptor binding.", "mechanism": "VEGF is upregulated in HCC, promoting angiogenesis and tumor progression; blockade enhances immune cell infiltration and potentiates immunotherapy.", "protein": "Vascular Endothelial Growth Factor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340405" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns (e.g., AFP-L3) are associated with HCC progression.", "mechanism": "AFP is elevated in HCC and used for diagnosis and monitoring.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340405" }, { "confidence": "medium", "disease": "Portal vein tumor thrombosis", "glycan_involvement": "Glycosylation modulates VEGF stability and activity.", "mechanism": "VEGF-driven angiogenesis contributes to vascular invasion and PVTT development.", "protein": "Vascular Endothelial Growth Factor", "relationship_type": "causal", "source_pmcid": "PMC12340405" }, { "confidence": "medium", "disease": "Portal vein tumor thrombosis", "glycan_involvement": "AFP glycoforms may indicate aggressive disease.", "mechanism": "Elevated AFP correlates with PVTT presence and tumor burden.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340405" }, { "confidence": "medium", "disease": "Virus-related hepatitis", "glycan_involvement": "Glycosylation affects VEGF secretion in inflamed liver tissue.", "mechanism": "VEGF is upregulated in hepatitis-induced HCC, and its inhibition improves immunotherapy efficacy.", "protein": "Vascular Endothelial Growth Factor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340405" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate infectivity.", "mechanism": "Spike protein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12340444" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects spike binding and viral entry efficiency.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2, facilitating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12340444" }, { "confidence": "medium", "disease": "Gastrointestinal manifestations in COVID-19", "glycan_involvement": "Glycosylation modulates tissue tropism and immune evasion.", "mechanism": "Spike protein enables viral infection of GI tract via ACE2-expressing cells.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12340444" }, { "confidence": "medium", "disease": "Gastrointestinal manifestations in COVID-19", "glycan_involvement": "N-glycosylation may influence ACE2 localization and viral interaction in GI tissues.", "mechanism": "ACE2 is highly expressed in GI tract; facilitates SARS-CoV-2 infection leading to GI symptoms.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12340444" }, { "confidence": "low", "disease": "End-stage renal disease (ESRD)", "glycan_involvement": "Altered glycosylation may affect immune recognition in ESRD.", "mechanism": "Spike-mediated infection exacerbates outcomes in ESRD patients.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12340444" }, { "confidence": "low", "disease": "End-stage renal disease (ESRD)", "glycan_involvement": "Potential changes in N-glycosylation in ESRD context.", "mechanism": "ACE2 expression and glycosylation may be altered in ESRD, impacting susceptibility.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12340444" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation (HbA1c) is a clinical marker for diabetes; altered glycosylation may affect function.", "mechanism": "Downregulated in diabetic glomeruli and peripheral blood; reflects molecular pathology and iron metabolism disturbance.", "protein": "HBA1", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation (HbA1c) relevant for diabetes monitoring.", "mechanism": "Downregulated in diabetic glomeruli and peripheral blood; associated with iron metabolism and oxygen transport.", "protein": "HBA2", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation (HbA1c) is a key diabetes biomarker.", "mechanism": "Downregulated in diabetic glomeruli and peripheral blood; involved in iron metabolism and oxygen binding.", "protein": "HBB", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "medium", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "No direct glycan modification reported; protein is a phosphoprotein, possible indirect glycan effects.", "mechanism": "Upregulated in diabetic cardiomyocytes; regulates apoptosis and ferroptosis, contributing to cardiac cell death.", "protein": "PEA15", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340516" }, { "confidence": "medium", "disease": "Diabetic nephropathy (tubules)", "glycan_involvement": "No direct glycan modification reported.", "mechanism": "Upregulated in diabetic kidney tubules; correlates with increased apoptosis and ferroptosis, and with renal dysfunction (creatinine, GFR).", "protein": "PEA15", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340516" }, { "confidence": "medium", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Predicted N-glycosylation sites; may affect stability and function.", "mechanism": "Upregulated in diabetic cardiomyocytes; involved in apoptosis and ferroptosis.", "protein": "TFPI2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340516" }, { "confidence": "medium", "disease": "Diabetic nephropathy (tubules)", "glycan_involvement": "Predicted N-glycosylation sites; may influence activity.", "mechanism": "Upregulated in diabetic kidney tubules and proximal convoluted tubule; associated with apoptosis, ferroptosis, and renal dysfunction.", "protein": "TFPI2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12340516" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "N-terminal glycation (non-enzymatic glycosylation) forms HbA1c.", "mechanism": "Glycosylated form (HbA1c) is a standard marker for glycemic control.", "protein": "HBA1", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "N-terminal glycation (non-enzymatic glycosylation) forms HbA1c.", "mechanism": "Glycosylated form (HbA1c) includes HBB; reflects average blood glucose.", "protein": "HBB", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "medium", "disease": "Diabetic nephropathy (proximal tubule)", "glycan_involvement": "N-glycosylation may affect secretion and stability.", "mechanism": "High expression in proximal convoluted tubule in early diabetic nephropathy; potential early marker.", "protein": "TFPI2", "relationship_type": "biomarker", "source_pmcid": "PMC12340516" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "NfL is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Elevated sNfL reflects neuronal/axonal injury in Alzheimer's disease.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "All-cause dementia", "glycan_involvement": "NfL glycosylation may influence its release and serum stability.", "mechanism": "Increased sNfL levels are associated with the emergence of dementia.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation may affect NfL's half-life and detection in serum.", "mechanism": "Higher sNfL levels correlate with cognitive deterioration.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "NfL glycosylation may modulate immune recognition and clearance.", "mechanism": "sNfL levels reflect axonal injury in MS.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "Glycosylation may influence NfL aggregation and serum levels.", "mechanism": "Elevated sNfL indicates neuronal damage in ALS.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "Neuronal injury", "glycan_involvement": "Glycosylation affects NfL solubility and detection.", "mechanism": "sNfL is released upon neuro-axonal injury.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Hyperglycemia may alter glycosylation patterns of NfL.", "mechanism": "Diabetes amplifies the association between MMA and sNfL, indicating increased neuronal vulnerability.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "medium", "disease": "Vitamin B12 deficiency", "glycan_involvement": "Altered B12 status may affect glycosylation indirectly.", "mechanism": "Vitamin B12 deficiency (reflected by high MMA) is associated with increased sNfL, indicating neuronal damage.", "protein": "Neurofilament light chain (NfL)", "relationship_type": "biomarker", "source_pmcid": "PMC12340706" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect stability and receptor interaction.", "mechanism": "Higher CSF FGF21 levels are associated with improved cognitive function in individuals aged \u226434 years, possibly via enhanced hippocampal synaptic plasticity and neuroprotection.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12340712" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation may modulate FGF21's ability to bind KLB/FGFR1 complex.", "mechanism": "In individuals aged >34 years, higher CSF FGF21 levels are associated with cognitive decline, potentially due to 'FGF21 resistance' and reduced KLB expression.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12340712" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may influence neuroprotective activity.", "mechanism": "FGF21 modulates astrocyte-neuron lactate shuttle and attenuates amyloid \u03b2-induced cytotoxicity.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12340712" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "KLB is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Reduced KLB expression in aging/hippocampal atrophy leads to impaired FGF21 signaling and cognitive decline.", "protein": "KLB (\u03b2-Klotho)", "relationship_type": "causal", "source_pmcid": "PMC12340712" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "FGF19 is a glycoprotein; glycosylation may affect neuroprotective properties.", "mechanism": "FGF19 overexpression alleviates neuronal damage and may protect cognitive function.", "protein": "FGF19", "protein_enriched": { "function": "Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component o", "gene_name": "CWC22", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HCG8" }, "relationship_type": "protective", "source_pmcid": "PMC12340712" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "FGF23 is a glycoprotein; glycosylation may affect CNS activity.", "mechanism": "FGF23 overexpression impairs hippocampal long-term potentiation, leading to cognitive and memory decline.", "protein": "FGF23", "relationship_type": "causal", "source_pmcid": "PMC12340712" }, { "confidence": "medium", "disease": "Chronic kidney disease-related cognitive impairment", "glycan_involvement": "Glycosylation may influence FGF23 stability and CNS effects.", "mechanism": "High FGF23 levels in CNS are associated with poor cognitive performance in CKD patients.", "protein": "FGF23", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12340712" }, { "confidence": "low", "disease": "Mild cognitive impairment", "glycan_involvement": "Glycosylation may affect domain-specific activity.", "mechanism": "Serum FGF19 levels correlate with specific cognitive domains (immediate memory, language) in depression; no correlation in CSF with MoCA in healthy males.", "protein": "FGF19", "protein_enriched": { "function": "Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component o", "gene_name": "CWC22", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HCG8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12340712" }, { "confidence": "low", "disease": "Mild cognitive impairment", "glycan_involvement": "Glycosylation may modulate neuroprotective effects.", "mechanism": "Serum FGF21 levels positively correlate with immediate memory in young depressive patients.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12340712" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect KLB's neuroprotective function.", "mechanism": "KLB inhibits \u03b2-amyloid plaque formation in hippocampus, protecting neurons.", "protein": "KLB (\u03b2-Klotho)", "relationship_type": "protective", "source_pmcid": "PMC12340712" }, { "confidence": "high", "disease": "Hepatobiliary disease", "glycan_involvement": "Cholinesterase is a glycoprotein; glycosylation affects its stability and secretion, but specific glycan changes not discussed.", "mechanism": "Abnormal (low) serum cholinesterase levels indicate pesticide exposure and are associated with increased risk of hepatobiliary disease.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "medium", "disease": "Fatty liver (hepatic steatosis)", "glycan_involvement": "No direct glycan modification discussed for this disease.", "mechanism": "Low cholinesterase levels correlate with fatty liver detected by ultrasound in exposed workers.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "medium", "disease": "Periductal fibrosis", "glycan_involvement": "No direct glycan modification discussed.", "mechanism": "Low cholinesterase levels associated with periductal fibrosis in agricultural workers.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "medium", "disease": "Cholangiocarcinoma (CCA)", "glycan_involvement": "No direct glycan modification discussed.", "mechanism": "Low cholinesterase levels are associated with suspected CCA on ultrasound, reflecting pesticide exposure risk.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycan modification discussed.", "mechanism": "Previous studies cited show low cholinesterase and pesticide exposure increase HCC risk.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "No direct glycan modification discussed.", "mechanism": "Low cholinesterase levels associated with cirrhosis in exposed populations.", "protein": "Serum cholinesterase", "relationship_type": "biomarker", "source_pmcid": "PMC12341068" }, { "confidence": "medium", "disease": "Hepatobiliary disease", "glycan_involvement": "Glycosylation may affect cholinesterase secretion and function, but not directly implicated.", "mechanism": "Pesticide exposure inhibits cholinesterase, leading to oxidative stress and liver injury.", "protein": "Serum cholinesterase", "relationship_type": "causal", "source_pmcid": "PMC12341068" }, { "confidence": "high", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux of chemotherapeutic drugs, reducing intracellular drug concentration.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "high", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation affects stability and trafficking.", "mechanism": "Efflux of drugs and metabolites, contributing to multidrug resistance.", "protein": "MRP-1 (ABCC1)", "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation modulates receptor function and ligand binding.", "mechanism": "IL-6/IL-6R signaling activates STAT3, promoting survival, stemness, and chemo-resistance.", "protein": "IL-6 receptor (IL-6R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation regulates integrin activation and cell adhesion.", "mechanism": "Mediates IL-6/STAT3-induced EMT and stemness, enhancing resistance.", "protein": "Integrin \u03b26", "protein_enriched": { "function": "Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin (PubMed:17158881, PubMed:17545607). It recognizes the sequence R-G-D in its ligands (PubMed:17158881, PubMed:17545607", "gene_name": "ITGB6", "glycan_count": 23, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G41071NU", "G60033FS", "G22573RC", "G02815KT", "G05724UK", "G20706XG", "G25451PN", "G27058EU", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G64527OM", "G70101JE", "G73291XG", "G80920RR", "G83460ZZ", "G84452RH", "G96577RX", "G45395BF", "G46503DX", "G57776ZS", "G49108TO" ], "uniprot_id": "P18564" }, "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Mediates TNF\u03b1 signaling, which can modulate ABC transporter expression and apoptosis.", "protein": "TNF receptor 1 (TNFR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation essential for receptor signaling.", "mechanism": "IL-1R1 mediates IL-1-induced MRP-1 expression and NO signaling, promoting drug efflux.", "protein": "IL-1 receptor (IL-1R1)", "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation required for surface expression.", "mechanism": "Efflux of chemotherapeutic agents, contributing to resistance.", "protein": "BCRP (ABCG2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Heavily glycosylated; glycan moieties mediate cell adhesion and immune evasion.", "mechanism": "Associated with stemness and oxaliplatin resistance.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "COX2 expression increases resistance via NFKB/p38-MAPK/ERK1/2/JNK signaling.", "protein": "COX2 (PTGS2)", "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "medium", "disease": "Chemo-resistance in colorectal cancer", "glycan_involvement": "N-glycosylation modulates receptor signaling.", "mechanism": "IL-1-induced IL-8 production acts via CXCR1/2 to promote survival and resistance.", "protein": "IL-8 receptor (CXCR1/2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341088" }, { "confidence": "high", "disease": "Anemia associated with chronic kidney disease (CKD)", "glycan_involvement": "EPO is a heavily glycosylated protein; glycosylation is essential for its stability and activity.", "mechanism": "Deficiency of EPO production by kidneys leads to anemia in CKD.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "causal", "source_pmcid": "PMC12341096" }, { "confidence": "high", "disease": "Anemia associated with chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation of EPO is required for its secretion and function.", "mechanism": "Vadadustat increases endogenous EPO production to stimulate erythropoiesis.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). 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Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341096" }, { "confidence": "medium", "disease": "Thromboembolic events", "glycan_involvement": "Glycosylation modulates EPO's pharmacokinetics and receptor interactions.", "mechanism": "ESA therapy increases risk of thromboembolic events in CKD patients.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341096" }, { "confidence": "low", "disease": "Pulmonary hypertension", "glycan_involvement": "Glycosylation status may influence EPO's tissue distribution.", "mechanism": "EPO/ESA therapy can be associated with pulmonary hypertension as an adverse event.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341096" }, { "confidence": "low", "disease": "Liver enzyme elevation (ALT/AST)", "glycan_involvement": "Glycosylation may affect hepatic clearance.", "mechanism": "Elevated liver enzymes observed as a possible adverse event during ESA therapy.", "protein": "Darbepoetin alfa", "relationship_type": "biomarker", "source_pmcid": "PMC12341096" }, { "confidence": "high", "disease": "Anemia associated with chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation is required for EPO detection in immunoassays.", "mechanism": "Serum EPO levels are used to monitor response to vadadustat and ESA therapy.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341096" }, { "confidence": "high", "disease": "Anemia associated with chronic kidney disease (CKD)", "glycan_involvement": "Proper glycosylation is necessary for EPO's erythropoietic activity.", "mechanism": "Endogenous EPO production (stimulated by vadadustat) protects against anemia.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "protective", "source_pmcid": "PMC12341096" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Predicted N-glycosylation and SUMOylation motifs in C-terminal region may facilitate nuclear import and stability in host cells.", "mechanism": "Promotes malignant transformation, reduces effectiveness of anticancer drugs, interacts with host USP7 and p53 pathways.", "protein": "DnaK", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "medium", "disease": "Tumor progression", "glycan_involvement": "SUMOylation and USP7-mediated deubiquitination motifs; N-glycosylation sites predicted.", "mechanism": "Facilitates adaptation to tumor microenvironment, possibly via post-translational modifications (SUMOylation, phosphorylation).", "protein": "DnaK", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Potential interaction with host glycans via surface exposure; no direct glycosylation reported.", "mechanism": "Surface-exposed Ef-Tu mediates adhesion and biofilm formation, promoting onset of periodontitis.", "protein": "Elongation factor Tu (Ef-Tu)", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Possible glycan-mediated host interactions; no direct glycosylation reported.", "mechanism": "Moonlighting functions in adhesion and invasion may facilitate Fusobacterium colonization in CRC.", "protein": "Elongation factor Tu (Ef-Tu)", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "low", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Variation in MinD may affect cell shape/size, influencing colonization and disease progression.", "protein": "MinD", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "low", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Modulates specificity of Clp protease, impacting stress tolerance and biofilm formation.", "protein": "ClpX", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341114" }, { "confidence": "low", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Enhanced binding to ribosomal protein L27 may affect ribosome maturation and bacterial fitness in tumor microenvironment.", "protein": "Prp", "relationship_type": "causal", "source_pmcid": "PMC12341114" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Amino acid replacements in RpoC associated with antibiotic resistance/adaptation.", "protein": "RpoC", "relationship_type": "biomarker", "source_pmcid": "PMC12341114" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Amino acid replacements linked to antibiotic resistance.", "protein": "Elongation factor Tu (Ef-Tu)", "relationship_type": "biomarker", "source_pmcid": "PMC12341114" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "SUMOylation and USP7-mediated deubiquitination motifs; N-glycosylation sites predicted.", "mechanism": "Targeting DnaK or its post-translational modifications may disrupt Fusobacterium's oncogenic potential.", "protein": "DnaK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341114" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation patterns may affect its diagnostic accuracy.", "mechanism": "Elevated serum AFP is used as a diagnostic marker for HCC.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341115" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Glycosylation status may influence AFP stability and detection.", "mechanism": "AFP levels may be elevated in CHB, especially with active liver regeneration or malignancy.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341115" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "HBeAg is glycosylated, which affects its secretion and immune recognition.", "mechanism": "HBeAg positivity indicates active viral replication and infectivity.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341115" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may modulate HBeAg's immunogenicity and persistence.", "mechanism": "HBeAg positivity is associated with increased risk of HCC in CHB patients.", "protein": "Hepatitis B e antigen (HBeAg)", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03141" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341115" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation changes may distinguish benign from malignant AFP elevation.", "mechanism": "AFP may be mildly elevated in cirrhosis due to liver regeneration.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341115" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "AST is glycosylated, affecting its stability and serum levels.", "mechanism": "Elevated AST is a component of liver fibrosis scores (FIB-4, NFS, APRI) associated with increased CVD risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "ALT glycosylation may influence enzyme activity and clearance.", "mechanism": "ALT is used in FIB-4 and NFS scores; altered levels reflect liver injury and systemic inflammation linked to CVD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation; altered glycosylation affects thrombosis risk.", "mechanism": "Platelet count (reflecting glycoprotein function) is part of FIB-4 and APRI scores, correlating with CVD risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Albumin glycosylation modulates antioxidant capacity and vascular health.", "mechanism": "Low albumin (included in NFS) is associated with poor outcomes in CVD and liver disease.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "IL-6 glycosylation affects receptor binding and inflammatory signaling.", "mechanism": "IL-6-driven inflammation contributes to both liver fibrosis and atherosclerosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "TNF-\u03b1 glycosylation modulates its bioactivity and systemic effects.", "mechanism": "TNF-\u03b1 promotes chronic inflammation, linking liver fibrosis and CVD.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341116" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation influences AST serum stability.", "mechanism": "Elevated AST is a marker of hepatic injury and fibrosis in NAFLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Altered glycosylation impacts platelet function in liver disease.", "mechanism": "Low platelet count reflects advanced liver fibrosis in NAFLD.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation modulates albumin's vascular and antioxidant properties.", "mechanism": "Low albumin is a marker of advanced NAFLD and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341116" }, { "confidence": "medium", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation affects IL-6 signaling in liver pathology.", "mechanism": "IL-6 mediates hepatic inflammation and fibrosis in NAFLD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12341116" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "N-glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated serum AST indicates hepatocellular damage.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "N-glycosylation modulates ALT secretion and activity.", "mechanism": "ALT elevation is a specific marker for liver cell injury.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation may alter AST immunogenicity and clearance.", "mechanism": "AST rises in systemic inflammation affecting liver or muscle.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation influences ALT serum levels.", "mechanism": "ALT increases in inflammatory liver conditions.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Altered glycosylation in diabetes may affect AST function.", "mechanism": "Mild AST elevation can occur in metabolic syndrome/diabetes.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Diabetes mellitus", "glycan_involvement": "Diabetes can alter ALT glycosylation patterns.", "mechanism": "ALT is sometimes elevated in diabetes due to fatty liver.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Allergic reaction", "glycan_involvement": "Glycosylation may affect AST immunogenicity.", "mechanism": "AST may rise in systemic allergic reactions with hepatic involvement.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Allergic reaction", "glycan_involvement": "Glycosylation status may modulate ALT response.", "mechanism": "ALT may rise in severe allergic reactions affecting the liver.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation may affect AST release from erythrocytes.", "mechanism": "AST can be released from red cells in hemolytic anemia.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation may influence ALT stability in serum.", "mechanism": "ALT may be mildly elevated in hemolytic states.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341169" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "sIL-6R is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "Elevated sIL-6R levels are associated with impaired IL-6 regulation, increased inflammation, and insulin resistance in T2DM.", "protein": "sIL-6R", "relationship_type": "biomarker", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "sgp130 is a glycoprotein; glycosylation modulates its ability to bind IL-6:sIL-6R complexes.", "mechanism": "Disrupted sgp130 levels impair IL-6 buffering, promoting proinflammatory signaling in T2DM.", "protein": "sgp130", "relationship_type": "biomarker", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "IL-6 is glycosylated, which affects its secretion and receptor interaction.", "mechanism": "Elevated IL-6 drives chronic inflammation and insulin resistance in T2DM.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12341209" }, { "confidence": "medium", "disease": "Cognitive Impairment", "glycan_involvement": "Glycosylation may influence sIL-6R stability and neuroinflammatory signaling.", "mechanism": "Higher sIL-6R levels correlate with worse cognitive performance (processing speed, visuospatial function) in T2DM.", "protein": "sIL-6R", "relationship_type": "biomarker", "source_pmcid": "PMC12341209" }, { "confidence": "medium", "disease": "Cognitive Impairment", "glycan_involvement": "Glycosylation affects sgp130's inhibitory function on IL-6 trans-signaling.", "mechanism": "Elevated sgp130 is associated with poorer cognitive domains in T2DM, possibly via dysregulated IL-6 signaling.", "protein": "sgp130", "relationship_type": "biomarker", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation modulates sIL-6R's interaction with IL-6 and downstream signaling.", "mechanism": "Elevated sIL-6R promotes IL-6 trans-signaling, exacerbating insulin resistance.", "protein": "sIL-6R", "relationship_type": "causal", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "Glycosylation is critical for sgp130's ligand binding and inhibitory activity.", "mechanism": "sgp130 buffers IL-6:sIL-6R complexes, limiting proinflammatory signaling; insufficient sgp130 leads to unchecked inflammation.", "protein": "sgp130", "relationship_type": "protective", "source_pmcid": "PMC12341209" }, { "confidence": "medium", "disease": "Cognitive Impairment", "glycan_involvement": "IL-6 glycosylation may affect neuroinflammatory potential.", "mechanism": "Elevated IL-6 is linked to increased risk of global cognitive decline in T2DM.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "Glycosylation influences sIL-6R's stability and signaling capacity.", "mechanism": "sIL-6R facilitates IL-6 trans-signaling, driving systemic inflammation in T2DM.", "protein": "sIL-6R", "relationship_type": "causal", "source_pmcid": "PMC12341209" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation required for sgp130's inhibitory function.", "mechanism": "sgp130 inhibits IL-6 trans-signaling, potentially mitigating insulin resistance.", "protein": "sgp130", "relationship_type": "protective", "source_pmcid": "PMC12341209" }, { "confidence": "high", "disease": "Synaptic dysfunction", "glycan_involvement": "Heparan sulfate glycosylation required for function", "mechanism": "Regulates AMPA receptor localization, stabilizing excitatory synapses", "protein": "Glypican 4", "protein_enriched": { "function": "Regulatory subunit of anion-selective CLCNKA:BSND and CLCNKB:BSND heteromeric channels involved in basolateral chloride conductance along the nephron to achieve urine concentration and maintain system", "gene_name": "Bsnd", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8VIM4" }, "relationship_type": "protective", "source_pmcid": "PMC12341218" }, { "confidence": "high", "disease": "Synaptic dysfunction", "glycan_involvement": "Heparan sulfate glycosylation required for activity", "mechanism": "Promotes AMPA receptor localization and synapse maturation", "protein": "Glypican 6", "protein_enriched": { "function": "Smooth muscle cells (SM) and cardiac muscle cells-specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence. Acts as a cofactor of serum response factor (SRF)", "gene_name": "Myocd", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8VIM5" }, "relationship_type": "protective", "source_pmcid": "PMC12341218" }, { "confidence": "high", "disease": "Developmental encephalopathy", "glycan_involvement": "N-glycosylation modulates secretion and synaptogenic activity", "mechanism": "Induces/stabilizes synaptic contacts during development", "protein": "Thrombospondin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12341218" }, { "confidence": "medium", "disease": "Synaptic dysfunction", "glycan_involvement": "N-glycosylation affects extracellular matrix interactions", "mechanism": "Regulates synaptic strength and maturation", "protein": "SPARCL1", "protein_enriched": { "function": "Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of th", "gene_name": "KARS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q15046" }, "relationship_type": "protective", "source_pmcid": "PMC12341218" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences lipid binding and neuronal uptake", "mechanism": "Stabilizes presynaptic function and vesicle number; ApoE4 variant increases risk", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal", "source_pmcid": "PMC12341218" }, { "confidence": "high", "disease": "Glutamatergic transmission disorders", "glycan_involvement": "N-glycosylation affects receptor trafficking and function", "mechanism": "Modulates excitatory synaptic transmission via Ca2+ signaling and vesicle recycling", "protein": "LPA 2 receptor (LPAR2)", "protein_enriched": { "function": "Endothelial orphan receptor that acts as a key regulator of angiogenesis", "gene_name": "ADGRL4", "glycan_count": 31, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G13694XX", "G25418HZ", "G31665QC", "G33791AF", "G47748JZ", "G74728JK", "G86500WE", "G89205CJ", "G05049YU", "G27058EU", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G62765YT", "G80920RR", "G81637OR", "G00912UN", "G04657PL", "G05962QB", "G08918WF", "G11629QQ", "G12793SR", "G15169WU", "G39471UU", "G46503DX", "G52527GH", "G55132BD", "G81263BG", "G93656SY", "G71142DF" ], "uniprot_id": "Q9HBW9" }, "relationship_type": "causal", "source_pmcid": "PMC12341218" }, { "confidence": "medium", "disease": "Cortical hyperexcitability", "glycan_involvement": "N-glycosylation required for secretion and enzymatic activity", "mechanism": "Generates LPA at excitatory synapses, modulating transmission", "protein": "Autotaxin (ENPP2)", "protein_enriched": { "function": "Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia", "gene_name": "GDA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q9Y2T3" }, "relationship_type": "causal", "source_pmcid": "PMC12341218" }, { "confidence": "medium", "disease": "Network excitability disorders", "glycan_involvement": "N-glycosylation modulates receptor binding and activity", "mechanism": "Regulates AMPA receptor localization and synaptic scaling", "protein": "TNF\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341218" }, { "confidence": "medium", "disease": "Epileptic encephalopathy", "glycan_involvement": "Putative N-glycosylation may affect membrane localization", "mechanism": "Controls phospholipid levels in synaptic cleft, affecting excitatory transmission", "protein": "Postsynaptic plasticity-related gene 1 (PRG1)", "relationship_type": "causal", "source_pmcid": "PMC12341218" }, { "confidence": "low", "disease": "Synaptic dysfunction", "glycan_involvement": "O-glycosylation may regulate vesicle trafficking", "mechanism": "Modulates vesicle fusion and recycling; altered function impairs neurotransmission", "protein": "Synaptobrevin (VAMP2)", "relationship_type": "causal", "source_pmcid": "PMC12341218" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "gE is glycosylated; glycosylation affects antigenicity and detection.", "mechanism": "gE is used to distinguish wild-type PRV infection from vaccine strains; gE deletion in vaccines enables serological differentiation.", "protein": "gE", "relationship_type": "biomarker", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation influences immune recognition and vaccine efficacy.", "mechanism": "gE deletion in vaccine strains (e.g., Bartha-K61, rPRVTJ-delgE) improves vaccine safety and enables DIVA strategy.", "protein": "gE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "gB mediates viral entry and cell fusion, essential for PRV infectivity and pathogenicity.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation affects immunogenicity and host interaction.", "mechanism": "gD is critical for receptor binding and induction of host antibody response.", "protein": "gD", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "medium", "disease": "Neurological disease in pigs", "glycan_involvement": "Glycosylation may affect neurotropism and immune evasion.", "mechanism": "gE contributes to neuroinvasion and establishment of lifelong latency in sensory ganglia.", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Altered glycosylation may change antigenicity and immune escape.", "mechanism": "gE sequence variants (insertions/substitutions) linked to vaccine escape and increased pathogenicity.", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "medium", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation may affect genotype-specific antigenicity.", "mechanism": "gC gene variability is used for PRV genotyping (I/II), tracking epidemiology.", "protein": "gC", "relationship_type": "biomarker", "source_pmcid": "PMC12341279" }, { "confidence": "medium", "disease": "Respiratory disease in pigs", "glycan_involvement": "Glycosylation may influence tissue targeting.", "mechanism": "gE is implicated in tissue tropism, including respiratory tract infection.", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation affects assay sensitivity/specificity.", "mechanism": "gE-based ELISA is the main serological assay for PRV surveillance.", "protein": "gE", "relationship_type": "biomarker", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Potential impact on glycosylation and immune escape.", "mechanism": "gE mutations (D insertion at 494, G\u2192D at 54) associated with reduced vaccine efficacy and increased prevalence.", "protein": "gE", "relationship_type": "causal", "source_pmcid": "PMC12341279" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "N-glycosylation affects serum stability and tumor-specific glycoforms may enhance specificity.", "mechanism": "Elevated AFP is associated with hepatocellular carcinoma; reflects tumor burden and dedifferentiation.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation modulates CEA's secretion and immune recognition.", "mechanism": "CEA is overexpressed and secreted in colorectal cancer; used for diagnosis and monitoring.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Altered N-glycosylation patterns in cancer may affect detection.", "mechanism": "CEA is elevated in gastric cancer; used as a non-specific tumor marker.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation influences serum levels and immunogenicity.", "mechanism": "CEA is elevated in some lung cancers, especially adenocarcinoma.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "O-glycosylation may affect fragment stability and detection.", "mechanism": "CYFRA-211 is released from tumor cells, especially in non-small cell lung cancer.", "protein": "Cytokeratin-19 fragment (CYFRA-211)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "medium", "disease": "Esophageal cancer", "glycan_involvement": "O-glycosylation may modulate fragment release.", "mechanism": "Elevated CYFRA-211 is associated with esophageal squamous cell carcinoma.", "protein": "Cytokeratin-19 fragment (CYFRA-211)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "N-glycosylation of HBsAg affects immune evasion and persistence.", "mechanism": "HBsAg positivity indicates chronic HBV infection, a major risk factor for hepatocellular carcinoma.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "low", "disease": "Gastric cancer", "glycan_involvement": "Cancer-specific glycoforms may enhance diagnostic specificity.", "mechanism": "AFP can be elevated in rare AFP-producing gastric cancers.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "low", "disease": "Esophageal cancer", "glycan_involvement": "N-glycosylation may affect detection sensitivity.", "mechanism": "CEA is sometimes elevated in esophageal cancer.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "low", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation may influence serum detection.", "mechanism": "Rarely, AFP is elevated in lung cancer with hepatoid differentiation.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12341305" }, { "confidence": "high", "disease": "Major Adverse Cardiovascular Events (MACEs)", "glycan_involvement": "HDL particles are glycosylated; glycosylation affects HDL function and cholesterol efflux.", "mechanism": "Low HDL-c is an independent predictor of MACEs; reduced HDL impairs reverse cholesterol transport and anti-inflammatory functions.", "protein": "High-Density Lipoprotein cholesterol (HDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12341332" }, { "confidence": "medium", "disease": "Major Adverse Cardiovascular Events (MACEs)", "glycan_involvement": "LDL glycosylation modulates uptake by macrophages and atherogenicity.", "mechanism": "Elevated LDL-c, especially in moderate-risk individuals, is associated with increased MACEs risk.", "protein": "Low-Density Lipoprotein cholesterol (LDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12341332" }, { "confidence": "medium", "disease": "Major Adverse Cardiovascular Events (MACEs)", "glycan_involvement": "Glycosylation of ApoA-I influences HDL structure and function.", "mechanism": "ApoA-I is the main protein in HDL; its function is crucial for cholesterol efflux and anti-atherogenic effects.", "protein": "Apolipoprotein A-I", "relationship_type": "protective", "source_pmcid": "PMC12341332" }, { "confidence": "medium", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "N-glycosylation of ApoB-100 affects LDL clearance and atherogenicity.", "mechanism": "ApoB-100 is essential for LDL structure; increased ApoB-100 promotes atherogenesis.", "protein": "Apolipoprotein B-100", "relationship_type": "causal", "source_pmcid": "PMC12341332" }, { "confidence": "high", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "HDL glycosylation modulates its anti-inflammatory properties.", "mechanism": "HDL-c mediates reverse cholesterol transport and anti-inflammatory effects, reducing ASCVD risk.", "protein": "High-Density Lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC12341332" }, { "confidence": "medium", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Altered glycosylation in MetS may impair HDL function.", "mechanism": "Low HDL-c is a diagnostic criterion for MetS and reflects increased cardiometabolic risk.", "protein": "High-Density Lipoprotein cholesterol (HDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12341332" }, { "confidence": "medium", "disease": "Ischemic Heart Disease (IHD)", "glycan_involvement": "Glycosylation state influences LDL retention in vessel walls.", "mechanism": "Elevated LDL-c promotes atherosclerosis, leading to IHD.", "protein": "Low-Density Lipoprotein cholesterol (LDL-c)", "relationship_type": "causal", "source_pmcid": "PMC12341332" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "HDL glycosylation may affect cerebrovascular protection.", "mechanism": "Higher HDL-c levels are associated with reduced stroke risk via vascular protection.", "protein": "High-Density Lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC12341332" }, { "confidence": "low", "disease": "Peripheral Artery Disease (PAD)", "glycan_involvement": "LDL glycosylation affects its atherogenic potential.", "mechanism": "Elevated LDL-c contributes to atherosclerosis in peripheral arteries.", "protein": "Low-Density Lipoprotein cholesterol (LDL-c)", "relationship_type": "causal", "source_pmcid": "PMC12341332" }, { "confidence": "low", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "ApoA-I glycosylation may be altered in MetS, impacting HDL function.", "mechanism": "ApoA-I supports HDL function; higher levels are protective against MetS complications.", "protein": "Apolipoprotein A-I", "relationship_type": "protective", "source_pmcid": "PMC12341332" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Indirect; CDH1/CDH2 are glycoproteins regulated by C/EBP\u03b1.", "mechanism": "Downregulation or methylation of C/EBP\u03b1 correlates with poor prognosis; C/EBP\u03b1 suppresses proliferation and EMT by regulating CDH1/CDH2 and cyclin D1.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341345" }, { "confidence": "high", "disease": "Liver Cancer (Hepatocellular Carcinoma)", "glycan_involvement": "EGFR and \u03b2-catenin are glycoproteins in the regulated pathway.", "mechanism": "Low C/EBP\u03b1 expression (via UPS, YY1, TNF-\u03b1, miR-182) promotes HCC growth; C/EBP\u03b1-saRNA inhibits EGFR/\u03b2-catenin pathway and EMT.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341345" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Cyclin D1 is a glycoprotein regulated by C/EBP\u03b1.", "mechanism": "Cytoplasmic mislocalization and silencing of C/EBP\u03b1 promotes PDAC; C/EBP\u03b1-saRNA restores expression, upregulates p21, downregulates cyclin D1, and inhibits tumor growth.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341345" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "Indirect; Wnt pathway components may be glycoproteins.", "mechanism": "Downregulation (often via promoter hypermethylation) in ~30% of cases; restricts Wnt signaling and regulates cell differentiation.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341345" }, { "confidence": "high", "disease": "Lung Cancer", "glycan_involvement": "LOXL2/LOXL3 and BCL-2 are glycoproteins.", "mechanism": "Downregulation promotes tumor progression; regulates LOXL2/LOXL3 transcription via Tip60, stabilizing BCL-2 and promoting growth/metastasis.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341345" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Mutations in C/EBP\u03b1 (loss of P42, retention of P30) drive leukemogenesis by blocking differentiation and promoting proliferation.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "causal", "source_pmcid": "PMC12341345" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "PPAR\u03b3 upregulates C/EBP\u03b1 via p53, inducing hepatic stellate cell apoptosis and inhibiting fibrosis.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "protective", "source_pmcid": "PMC12341345" }, { "confidence": "medium", "disease": "Cisplatin Resistance in SCLC", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "TRIB2 overexpression downregulates C/EBP\u03b1, contributing to cisplatin resistance.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341345" }, { "confidence": "medium", "disease": "Colorectal Inflammatory Bowel Disease (IBD)", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Abnormal C/EBP\u03b1 expression in intestinal epithelial cells modulates inflammatory cell recruitment and disease progression.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341345" }, { "confidence": "medium", "disease": "Tumor Metastasis", "glycan_involvement": "Indirect; ZBTB7A may regulate glycoprotein expression.", "mechanism": "C/EBP\u03b1 and miR-100 promoter inhibit metastasis in gastric cancer by targeting ZBTB7A.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341345" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Klotho's glycoside hydrolase domains modify glycosylation of target proteins, influencing cardiac function.", "mechanism": "Reduces oxidative stress, cardiac remodeling, and apoptosis; supplementation prevents heart failure in mouse models.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12341567" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Klotho modifies glycosylation patterns on vascular proteins, impacting calcification and inflammation.", "mechanism": "Higher Klotho levels inversely associated with carotid intima-media thickness; regulates vascular smooth muscle cell homeostasis.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12341567" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Klotho regulates glycosylation of renal ion channels (TRPV5, ROMK1), affecting kidney function.", "mechanism": "Klotho deficiency is common in CKD; supplementation protects against progression and cardiac remodeling.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12341567" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Klotho modulates glycosylation of metabolic regulators and vascular proteins.", "mechanism": "Klotho deficiency exacerbates inflammation and atherosclerosis in diabetes; higher levels reduce risk.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12341567" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Klotho may influence glycosylation of neuronal proteins involved in amyloid processing.", "mechanism": "Peripheral and central Klotho administration improves cognition and reduces amyloid-\u03b2 levels in mouse models.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12341567" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Klotho regulates glycosylation of ion channels affecting vascular tone.", "mechanism": "Low serum Klotho is an independent risk factor for cardiovascular mortality in hypertensive patients.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12341567" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Klotho modifies glycosylation of metabolic regulators.", "mechanism": "Serum Klotho levels inversely associated with metabolic syndrome prevalence and mortality risk.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12341567" }, { "confidence": "high", "disease": "Acute Kidney Injury", "glycan_involvement": "Klotho regulates glycosylation of renal and cardiac proteins.", "mechanism": "Klotho supplementation prevents AKI and protects against cardiac remodeling in mouse models.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341567" }, { "confidence": "medium", "disease": "Coronary Artery Disease", "glycan_involvement": "Klotho modifies glycosylation of vascular proteins.", "mechanism": "Genetically higher circulating Klotho levels inversely associated with CAD risk.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12341567" }, { "confidence": "medium", "disease": "Atrial Fibrillation", "glycan_involvement": "Klotho may regulate glycosylation of cardiac ion channels.", "mechanism": "Higher genetically predicted Klotho levels inversely associated with atrial fibrillation risk.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC12341567" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "LSECtin is a C-type lectin glycoprotein; its glycan-binding domain mediates immune modulation.", "mechanism": "LSECtin overexpression attenuates liver damage, reduces fibrosis, and improves liver function in cirrhosis by modulating T cell responses.", "protein": "LSECtin (CLEC4G)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12341605" }, { "confidence": "high", "disease": "Th17-mediated hepatic inflammation", "glycan_involvement": "Glycosylation enables LSECtin's lectin activity and interaction with LAG-3.", "mechanism": "LSECtin downregulation leads to expansion of proinflammatory Th17 cells; restoring LSECtin suppresses Th17 differentiation via LAG-3.", "protein": "LSECtin (CLEC4G)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341605" }, { "confidence": "high", "disease": "Necroptosis-associated liver injury", "glycan_involvement": "Lectin domain function depends on glycosylation for immune regulation.", "mechanism": "LSECtin overexpression reduces necroptosis markers (Ripk3, Mlkl) and proinflammatory cell death in cirrhosis.", "protein": "LSECtin (CLEC4G)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12341605" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "LAG-3 is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "LAG-3 is upregulated on hepatic Th17 cells in cirrhosis; mediates LSECtin-dependent suppression of Th17 differentiation.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341605" }, { "confidence": "high", "disease": "Liver inflammation", "glycan_involvement": "IL-17 is a glycoprotein cytokine; glycosylation affects stability and secretion.", "mechanism": "IL-17-producing Th17 cells drive hepatic inflammation and fibrosis; expansion is restrained by LSECtin-LAG-3 signaling.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "causal", "source_pmcid": "PMC12341605" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Foxp3 is glycosylated; glycosylation may influence stability and function.", "mechanism": "LSECtin overexpression promotes regulatory Foxp3+ T cell differentiation, shifting immune response from proinflammatory to tolerogenic.", "protein": "Foxp3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12341605" }, { "confidence": "medium", "disease": "Necroptosis-associated liver injury", "glycan_involvement": "Ripk3 is glycosylated; glycosylation may affect kinase activity.", "mechanism": "Ripk3 upregulation promotes necroptosis and liver injury in cirrhosis; LSECtin overexpression reduces Ripk3 expression.", "protein": "Ripk3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341605" }, { "confidence": "medium", "disease": "Necroptosis-associated liver injury", "glycan_involvement": "Mlkl is glycosylated; glycosylation may regulate function.", "mechanism": "Mlkl phosphorylation mediates necroptosis; LSECtin overexpression reduces p-Mlkl and necroptotic cell death.", "protein": "Mlkl", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12341605" }, { "confidence": "low", "disease": "Cirrhosis", "glycan_involvement": "CD44 is heavily glycosylated; glycosylation mediates ligand binding.", "mechanism": "CD44 is a ligand for LSECtin; interaction relates to cell migration/adhesion, not direct immune inhibition.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341605" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "PD-1 is glycosylated; glycosylation affects checkpoint function.", "mechanism": "PD-1 expression marks regulatory T cell phenotype; increased in LSECtin-overexpressing mice.", "protein": "PD-1 (Pdcd1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341605" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation is essential for secretion and antigenicity of HBsAg.", "mechanism": "Serum HBsAg is a diagnostic marker for HBV infection and persistence.", "protein": "HBV S protein (surface antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Proper glycosylation required for immunogenicity and vaccine efficacy.", "mechanism": "Induction of anti-HBs antibodies via vaccination leads to viral clearance.", "protein": "HBV S protein (surface antigen)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12341611" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation affects antigen presentation and immune recognition.", "mechanism": "T cell responses against L protein contribute to viral control.", "protein": "HBV L protein (large envelope)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Not glycosylated; antigenicity independent of glycan.", "mechanism": "Anti-HBc antibodies indicate exposure and immune response to HBV.", "protein": "HBV Core protein", "protein_enriched": { "function": "The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and proc", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6F5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Not glycosylated.", "mechanism": "Core-specific CD8 T cell responses mediate clearance of infected hepatocytes.", "protein": "HBV Core protein", "protein_enriched": { "function": "The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and proc", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6F5" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12341611" }, { "confidence": "medium", "disease": "Chronic Hepatitis B", "glycan_involvement": "Not glycosylated.", "mechanism": "RT-specific T cell responses broaden immune control and may aid clearance.", "protein": "HBV Polymerase (RT domain)", "protein_enriched": { "function": "Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-bin", "gene_name": "calm", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02594" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation affects secretion and immune tolerance.", "mechanism": "Serum HBeAg indicates active viral replication and infectivity.", "protein": "HBV HBeAg (e antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12341611" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect immune evasion and chronicity.", "mechanism": "Persistent HBsAg expression is associated with increased risk of liver cancer.", "protein": "HBV S protein (surface antigen)", "relationship_type": "causal", "source_pmcid": "PMC12341611" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation required for secretion and persistence.", "mechanism": "Chronic HBV infection (persistent HBsAg) leads to liver inflammation and fibrosis.", "protein": "HBV S protein (surface antigen)", "relationship_type": "causal", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation critical for vaccine antigenicity.", "mechanism": "Vaccination-induced anti-HBs antibodies neutralize virus and prevent infection.", "protein": "HBV S protein (surface antigen)", "relationship_type": "protective", "source_pmcid": "PMC12341611" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "UCP1 is a mitochondrial glycoprotein; glycosylation may affect stability and function", "mechanism": "Promotes thermogenesis and energy expenditure via WAT browning, reducing obesity", "protein": "UCP1", "protein_enriched": { "function": "Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and", "gene_name": "UCP1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P25874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "HSF1 is glycosylated, which may regulate its transcriptional activity", "mechanism": "Activation of HSF1 by local hyperthermia induces WAT browning and thermogenesis", "protein": "HSF1", "protein_enriched": { "function": "Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large ", "gene_name": "HSF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G86339HP" ], "uniprot_id": "Q00613" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "PGC1\u03b1 is a glycoprotein; glycosylation may modulate coactivator function", "mechanism": "Upregulation of PGC1\u03b1 drives adaptive thermogenic programs in adipose tissue", "protein": "PGC1\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "HSP72 glycosylation may affect chaperone activity", "mechanism": "Induced by HSF1, HSP72 protects cells from stress and enhances metabolic processes", "protein": "HSP72", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54652" }, "relationship_type": "protective", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "CIDEA is a glycoprotein; glycosylation may influence adipocyte function", "mechanism": "Upregulated during WAT browning, indicating increased thermogenic capacity", "protein": "CIDEA", "protein_enriched": { "function": "Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recy", "gene_name": "DNAJC7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99615" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "SIRT1 is glycosylated, which may regulate its deacetylase activity", "mechanism": "SIRT1 upregulation is associated with improved metabolic health and WAT browning", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "ATGL glycosylation may affect enzyme activity", "mechanism": "Upregulation enhances lipolysis, improving lipid metabolism", "protein": "ATGL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "HSL is glycosylated, influencing lipase function", "mechanism": "Upregulation increases breakdown of stored triglycerides", "protein": "HSL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Lipid metabolism disorder", "glycan_involvement": "PPAR\u03b1 glycosylation may modulate receptor activity", "mechanism": "Activation promotes fatty acid oxidation and improves lipid profiles", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341637" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Albumin is N-glycosylated; glycan changes can indicate liver dysfunction", "mechanism": "Serum albumin levels reflect liver synthetic function; decreased in liver injury", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341637" }, { "confidence": "high", "disease": "Drug-induced immune thrombocytopenia (DITP)", "glycan_involvement": "Glycosylation of IIb/IIIa may affect antigenicity and antibody binding.", "mechanism": "Drug-dependent antibodies bind to platelet glycoprotein IIb/IIIa in the presence of certain drugs, leading to immune-mediated platelet destruction.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12341647" }, { "confidence": "high", "disease": "Immune thrombocytopenic purpura (ITP)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies (IgG) target glycoprotein IIb/IIIa, leading to platelet clearance.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC12341647" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "N-glycosylation affects antigenicity and secretion.", "mechanism": "HBsAg is used to diagnose and monitor HBV infection and response to therapy.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "N-glycosylation modulates immune recognition and secretion.", "mechanism": "HBeAg presence indicates active viral replication and infectivity.", "protein": "HBeAg", "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "high", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Contains glycosylated components affecting detection.", "mechanism": "HBcrAg reflects intrahepatic cccDNA activity and viral replication.", "protein": "HBcrAg", "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Altered glycosylation may affect oncogenicity.", "mechanism": "Persistent HBsAg positivity is associated with increased HCC risk.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "causal", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Low-level viremia (LLV)", "glycan_involvement": "Glycosylation affects immune evasion.", "mechanism": "HBeAg positivity is common in LLV and indicates ongoing viral replication.", "protein": "HBeAg", "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Low-level viremia (LLV)", "glycan_involvement": "Glycosylation impacts antigen stability and detection.", "mechanism": "HBcrAg levels correlate with LLV and risk of disease progression.", "protein": "HBcrAg", "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Chronic hepatitis B (CHB)", "glycan_involvement": "Potential glycosylation may affect capsid assembly and drug binding.", "mechanism": "HBcAg is targeted by GST-HG141 to modulate capsid assembly and block viral replication.", "protein": "HBcAg", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation may influence immune response and fibrogenesis.", "mechanism": "Persistent HBsAg is associated with progression to cirrhosis.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation affects antigen detection and stability.", "mechanism": "High HBcrAg levels predict increased risk of HCC.", "protein": "HBcrAg", "relationship_type": "biomarker", "source_pmcid": "PMC12341701" }, { "confidence": "medium", "disease": "Low-level viremia (LLV)", "glycan_involvement": "Glycosylation may modulate capsid structure and drug efficacy.", "mechanism": "GST-HG141 binds HBcAg, stabilizing capsid and reducing LLV.", "protein": "HBcAg", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341701" }, { "confidence": "high", "disease": "B cell acute lymphoblastic leukemia (ALL)", "glycan_involvement": "GP101 is a secreted glycoprotein; glycosylation may affect stability and serum half-life.", "mechanism": "Engages T cells to kill CD19+ B cells via bispecific diabody activity.", "protein": "GP101", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell lymphoma", "glycan_involvement": "Glycosylation may influence secretion and immune recognition.", "mechanism": "Redirects T cells to eliminate CD19+ lymphoma cells.", "protein": "GP101", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell acute lymphoblastic leukemia (ALL)", "glycan_involvement": "CD19 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "CD19 is the target antigen for GP101 and blinatumomab-mediated T cell engagement.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell lymphoma", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "CD19 is targeted for T cell-mediated cytotoxicity.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell acute lymphoblastic leukemia (ALL)", "glycan_involvement": "Glycosylation impacts pharmacokinetics and immunogenicity.", "mechanism": "Bispecific T cell engager links CD3+ T cells to CD19+ B cells for cytotoxicity.", "protein": "Blinatumomab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell lymphoma", "glycan_involvement": "Glycosylation affects serum half-life.", "mechanism": "Facilitates T cell-mediated killing of CD19+ lymphoma cells.", "protein": "Blinatumomab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "B cell depletion (secondary to therapy)", "glycan_involvement": "IVIG is a glycoprotein; glycosylation critical for function.", "mechanism": "IVIG is used to maintain immunoglobulin levels after B cell ablation.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "protective", "source_pmcid": "PMC12341704" }, { "confidence": "medium", "disease": "B cell lymphoma", "glycan_involvement": "Fc glycosylation modulates half-life and effector function.", "mechanism": "Bispecific antibody targeting CD3 and CD20 for T cell engagement.", "protein": "Glofitimab-gxbm", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation may affect therapeutic efficacy and immunogenicity.", "mechanism": "Potential to deplete autoreactive B cells by targeting CD19.", "protein": "GP101", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12341704" }, { "confidence": "medium", "disease": "Thrombotic microangiopathy", "glycan_involvement": "Capsid glycosylation may influence immunogenicity.", "mechanism": "Anti-AAV antibodies (potentially glycan-dependent) implicated in pathogenesis.", "protein": "AAV capsid glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12341704" }, { "confidence": "high", "disease": "A-GFAP-A", "glycan_involvement": "GFAP glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Autoantibodies against GFAP in CSF drive autoimmune astrocytopathy, leading to CNS inflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "causal", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "A-GFAP-A", "glycan_involvement": "MOG is a glycoprotein; glycosylation modulates immune recognition.", "mechanism": "Co-occurrence of MOG-IgG autoantibodies in some A-GFAP-A patients suggests overlapping autoimmune pathology.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "NMOSD", "glycan_involvement": "AQP4 glycosylation influences antibody binding and pathogenicity.", "mechanism": "AQP4-IgG autoantibodies cause astrocyte damage in NMOSD; occasionally overlap with A-GFAP-A.", "protein": "AQP4", "relationship_type": "causal", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "Autoimmune Encephalitis", "glycan_involvement": "NMDAR glycosylation affects receptor function and immunogenicity.", "mechanism": "NMDAR-IgG detected in some A-GFAP-A patients, associated with increased seizure risk.", "protein": "NMDAR", "relationship_type": "biomarker", "source_pmcid": "PMC12341804" }, { "confidence": "low", "disease": "Autoimmune Encephalitis", "glycan_involvement": "Glycosylation modulates mGluR5 surface expression and immune response.", "mechanism": "mGluR5-IgG found in some A-GFAP-A cases, indicating possible overlap syndrome.", "protein": "mGluR5", "relationship_type": "biomarker", "source_pmcid": "PMC12341804" }, { "confidence": "high", "disease": "A-GFAP-A", "glycan_involvement": "CRP is glycosylated; glycan moieties affect its stability and immune function.", "mechanism": "Elevated CRP levels predict ICU admission and disease severity in A-GFAP-A.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "A-GFAP-A", "glycan_involvement": "ApoAI glycosylation influences lipid transport and immune modulation.", "mechanism": "Lower ApoAI levels associated with ICU admission, possibly reflecting systemic inflammation.", "protein": "ApoAI", "relationship_type": "biomarker", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "Epilepsy/Seizures", "glycan_involvement": "Altered glycosylation may affect GFAP aggregation and immune recognition.", "mechanism": "GFAP autoimmunity may contribute to seizure development via astrocyte dysfunction.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "causal", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "Myelitis", "glycan_involvement": "Glycosylation may modulate GFAP immunogenicity.", "mechanism": "GFAP autoantibodies drive spinal cord inflammation and myelitis.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "causal", "source_pmcid": "PMC12341804" }, { "confidence": "medium", "disease": "Meningitis", "glycan_involvement": "Potential role for glycosylation in antigen presentation.", "mechanism": "GFAP autoimmunity leads to meningeal inflammation in A-GFAP-A.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "causal", "source_pmcid": "PMC12341804" }, { "confidence": "high", "disease": "Immunoglobulin A vasculitis (IgAV)", "glycan_involvement": "Aberrant glycosylation of IgA1 is implicated in pathogenesis.", "mechanism": "IgA immune complex deposition in small vessels triggers vasculitis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC12341987" }, { "confidence": "high", "disease": "IgA vasculitis nephritis (IgAVN)", "glycan_involvement": "Altered O-glycosylation of IgA1 increases nephritogenicity.", "mechanism": "IgA immune complexes deposit in glomeruli, causing nephritis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC12341987" }, { "confidence": "high", "disease": "IgA vasculitis nephritis (IgAVN)", "glycan_involvement": "Albumin is N-glycosylated; loss in urine reflects glomerular barrier dysfunction.", "mechanism": "Low serum albumin reflects proteinuria and glomerular injury; higher levels are protective.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12341987" }, { "confidence": "medium", "disease": "IgA vasculitis nephritis (IgAVN)", "glycan_involvement": "IgG is N-glycosylated; glycosylation may modulate immune complex formation.", "mechanism": "Altered IgG levels associated with renal involvement.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "medium", "disease": "IgA vasculitis nephritis (IgAVN)", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its function.", "mechanism": "CRP levels reflect systemic inflammation; lower CRP associated with IgAVN in this cohort.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "high", "disease": "Immunoglobulin A nephropathy (IgAN)", "glycan_involvement": "Aberrant O-glycosylation of IgA1 is central to pathogenesis.", "mechanism": "IgA1 immune complexes deposit in glomeruli, causing nephropathy.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC12341987" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Loss of glycosylated albumin in urine reflects glomerular injury.", "mechanism": "Hypoalbuminemia indicates ongoing proteinuria and renal dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "medium", "disease": "End-stage renal disease (ESRD)", "glycan_involvement": "Loss of glycosylated albumin in urine.", "mechanism": "Persistent hypoalbuminemia is associated with progression to ESRD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "low", "disease": "Immunoglobulin A vasculitis (IgAV)", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "Altered IgG levels may reflect immune dysregulation in IgAV.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "low", "disease": "Immunoglobulin A vasculitis (IgAV)", "glycan_involvement": "N-glycosylation affects CRP function.", "mechanism": "CRP is an acute-phase reactant elevated in systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12341987" }, { "confidence": "high", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "Plasmablasts are glycoprotein-rich; altered glycosylation may affect antibody secretion and cell survival.", "mechanism": "Serve as major viral reservoirs with impaired antibody production, facilitating viral spread and severity in aged hosts.", "protein": "MKI67+ PB1 (defective plasmablasts)", "relationship_type": "causal", "source_pmcid": "PMC12342286" }, { "confidence": "high", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "B cell surface glycoproteins mediate activation and differentiation; altered glycosylation may impact function.", "mechanism": "Non-specific activation leads to defective plasmablast differentiation and immune dysregulation in aged hosts.", "protein": "T-bet+ ABCs (age-associated memory B cells)", "relationship_type": "causal", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "BCMA is a glycoprotein receptor; glycosylation may modulate ligand binding and signaling.", "mechanism": "Upregulated in memory B cells and plasmablasts, promoting B cell activation and survival independent of antigen.", "protein": "BCMA (TNFRSF17)", "protein_enriched": { "function": "Acts as an acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GSDMD, GAP43, ZDHHC6 or HRAS (PubMed:21152083, PubMed:2882", "gene_name": "LYPLA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95372" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "TACI glycosylation may affect receptor function and B cell signaling.", "mechanism": "Upregulated in memory B cells, facilitating non-specific B cell activation and defective differentiation.", "protein": "TACI (TNFRSF13B)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "CD38 glycosylation affects cell adhesion and signaling.", "mechanism": "Marker of plasmablasts; increased CD38+ PB1 cells correlate with viral load and disease severity.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "Glycosylation modulates BCR signaling and B cell survival.", "mechanism": "B cell marker used to identify infected B cell subsets; depletion correlates with immune collapse.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "Glycosylation may influence receptor-ligand interactions.", "mechanism": "Marker for plasmablasts; loss of CD27+ B cells reflects impaired humoral immunity.", "protein": "CD27", "protein_enriched": { "function": "Costimulatory immune-checkpoint receptor expressed at the surface of T-cells, NK-cells and B-cells which binds to and is activated by its ligand CD70/CD27L expressed by B-cells (PubMed:28011863). The ", "gene_name": "CD27", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G22310AV", "G64275UO", "G91473PK" ], "uniprot_id": "P26842" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)-like pathology", "glycan_involvement": "CALR is a glycoprotein; glycosylation may affect its cell-surface exposure and phagocytic signaling.", "mechanism": "Upregulated as an 'eat-me' signal on dying immune cells, promoting hemophagocytosis and immune cell depletion.", "protein": "Calreticulin (CALR)", "relationship_type": "causal", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)-like pathology", "glycan_involvement": "Glycosylation may modulate membrane binding and phagocytic signaling.", "mechanism": "Acts as an 'eat-me' signal, facilitating phagocytosis of immune cells and contributing to cytopenias.", "protein": "Annexin A1 (ANXA1)", "relationship_type": "causal", "source_pmcid": "PMC12342286" }, { "confidence": "medium", "disease": "Severe Fever with Thrombocytopenia Syndrome (SFTS)", "glycan_involvement": "Glycosylation affects integrin-mediated adhesion and signaling.", "mechanism": "Marker for activated B cells (T-bet+ ABCs); increased CD11c+ B cells indicate aberrant activation in aged hosts.", "protein": "CD11c", "protein_enriched": { "function": "Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antige", "gene_name": "FCER2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P06734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12342286" }, { "confidence": "high", "disease": "Botulism", "glycan_involvement": "CPS is a glycan-rich surface structure; glycosylation is essential for capsule formation.", "mechanism": "CPS biosynthesis genes are conserved in pathogenic strains, likely mediating immune evasion and colonization.", "protein": "Capsular Polysaccharide (CPS) biosynthesis proteins", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "high", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Glycosylation of capsule critical for pathogenicity.", "mechanism": "CPS cluster present in NEC strains, likely contributing to virulence via immune evasion.", "protein": "Capsular Polysaccharide (CPS) biosynthesis proteins", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "medium", "disease": "Botulism", "glycan_involvement": "Nonulosonic acid glycosylation of flagella.", "mechanism": "Flagellar glycosylation genes present in pathogenic strains, possibly enhancing motility and host colonization.", "protein": "Flagellar glycoproteins (with nonulosonic acid modifications)", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "medium", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Flagellar glycan modifications.", "mechanism": "Flagellar glycosylation may aid colonization and immune evasion in NEC.", "protein": "Flagellar glycoproteins (with nonulosonic acid modifications)", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "high", "disease": "Botulism", "glycan_involvement": "BoNT/E is associated with glycoprotein complexes for stability and delivery.", "mechanism": "BoNT/E operon is the direct cause of botulism in C. butyricum strains.", "protein": "Botulinum Neurotoxin E (BoNT/E) complex", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "medium", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Cleavage of sialic acid from host glycans.", "mechanism": "Production of neuraminidases implicated in NEC pathogenesis.", "protein": "Neuraminidases", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "low", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Potential glycosylation may affect activity.", "mechanism": "Haemolysin-like proteins contribute to tissue damage in NEC.", "protein": "Haemolysin-like polypeptides", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "medium", "disease": "Botulism", "glycan_involvement": "Catabolism of host-derived fucosylated glycans.", "mechanism": "Enable utilization of mucin-derived fucose, enhancing colonization.", "protein": "L-fucose utilization proteins", "relationship_type": "protective/competitive advantage", "source_pmcid": "PMC12342839" }, { "confidence": "medium", "disease": "Necrotizing Enterocolitis (NEC)", "glycan_involvement": "Breakdown of mucin glycans.", "mechanism": "Fucose utilization may provide colonization advantage in NEC strains.", "protein": "L-fucose utilization proteins", "relationship_type": "protective/competitive advantage", "source_pmcid": "PMC12342839" }, { "confidence": "high", "disease": "Botulism", "glycan_involvement": "Catalyze glycan assembly in capsule.", "mechanism": "Glycosyltransferases assemble CPS, facilitating immune evasion.", "protein": "Glycosyltransferases (CPS locus)", "relationship_type": "causal", "source_pmcid": "PMC12342839" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "TREM2 is a glycoprotein; glycosylation may affect folding and function.", "mechanism": "Missense mutations in TREM2 alter protein structure, contributing to disease pathogenesis.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12342994" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "CD33 is a sialic acid-binding glycoprotein; glycosylation modulates ligand binding.", "mechanism": "Missense mutations in CD33 affect structure and function, influencing disease risk.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12342994" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation affects aggregation propensity.", "mechanism": "Tau aggregation is central to disease; peptide inhibitors can block aggregation.", "protein": "Tau protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike protein interaction.", "mechanism": "ACE2 is the viral entry receptor; mutations and glycosylation affect SARS-CoV-2 binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Protease is glycosylated; glycosylation may affect inhibitor binding.", "mechanism": "Protease is essential for viral replication; inhibitors block its function.", "protein": "SARS-CoV-2 main protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "Monkeypox", "glycan_involvement": "Predicted glycosylation may affect substrate recognition.", "mechanism": "Protease required for viral maturation; inhibitors designed based on structure.", "protein": "I7L protease (Monkeypox virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "high", "disease": "Bacterial infection (Aeromonas hydrophila)", "glycan_involvement": "Carbohydrate binding module recognizes host fucosylated glycans.", "mechanism": "Adhesin mediates host attachment via fucosylated glycan binding.", "protein": "Aeromonas hydrophila RTX adhesin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "Plant viral diseases", "glycan_involvement": "Predicted glycosylation may affect DNA binding and stability.", "mechanism": "PLATZ acts as a transcription factor regulating plant immunity.", "protein": "PLATZ (plant zinc-binding protein)", "relationship_type": "protective", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "Small round cell sarcoma", "glycan_involvement": "Glycosylation may regulate conformational state and substrate recognition.", "mechanism": "Conformational state changes in disease; structure prediction aids pathogenesis study.", "protein": "E3 ubiquitin ligase", "relationship_type": "biomarker", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "General viral infection (e.g., SARS-CoV-2)", "glycan_involvement": "N-glycosylation modulates receptor conformation and function.", "mechanism": "GPCRs are drug targets; glycosylation affects ligand binding and signaling.", "protein": "G protein-coupled receptors (GPCRs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12342994" }, { "confidence": "medium", "disease": "Colorectal interval polyposis", "glycan_involvement": "Altered N-glycosylation affects CEA detection and tumor progression.", "mechanism": "Elevated CEA levels are associated with increased risk of interval polyposis and colorectal neoplasia.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "medium", "disease": "Colorectal interval polyposis", "glycan_involvement": "Mucin-type O-glycosylation influences antigenicity and detection.", "mechanism": "CA199 is used as a serological marker for colorectal neoplasia risk.", "protein": "Cancer Antigen 199 (CA199)", "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "O-glycosylation modulates immune recognition.", "mechanism": "Elevated CA125 may indicate increased risk of polyposis.", "protein": "Cancer Antigen 125 (CA125)", "protein_enriched": { "function": "May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the", "gene_name": "DEDD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WXF8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "N-glycosylation affects serum stability and detection.", "mechanism": "AFP is measured as a tumor marker in colorectal neoplasia.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "N-glycosylation may influence half-life and function.", "mechanism": "Serum albumin levels are monitored for disease risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "Glycosylation affects immune function.", "mechanism": "Serum globulin ratio is used in risk assessment.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "N-glycosylation modulates coagulation activity.", "mechanism": "Fibrinogen levels may reflect inflammation and risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "N-glycosylation affects iron transport and detection.", "mechanism": "Transferrin is measured for nutritional and disease status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "N-glycosylation modulates immune effector functions.", "mechanism": "IgG levels may be altered in inflammatory states associated with polyposis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "low", "disease": "Colorectal interval polyposis", "glycan_involvement": "O-glycosylation is critical for mucin function and immune evasion.", "mechanism": "MUC1 is implicated in mucosal barrier and tumor progression.", "protein": "Mucin 1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12343215" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation modulates CRP stability and function", "mechanism": "Reflects systemic inflammation in sepsis", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects serum half-life", "mechanism": "Elevated in bacterial infection and sepsis", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation status affects vascular permeability", "mechanism": "Hypoalbuminemia indicates severity and poor prognosis", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation modulates clotting function", "mechanism": "Acute phase reactant; elevated in inflammation and coagulopathy", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "O-glycosylation affects peptide stability", "mechanism": "Elevated in cardiac dysfunction", "protein": "N-terminal pro-B-type natriuretic peptide (NT-proBNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may affect immunoassay detection", "mechanism": "Released during cardiac injury", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for secretion", "mechanism": "Pro-inflammatory cytokine elevated in sepsis", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates receptor binding", "mechanism": "Drives systemic inflammation and organ dysfunction", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12343221" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects solubility and immune function", "mechanism": "Altered levels reflect immune response", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect enzyme activity", "mechanism": "Elevated in tissue hypoxia and cell damage", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12343221" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "N-glycosylation affects AST stability and secretion.", "mechanism": "Elevated AST indicates hepatocellular injury due to alcohol.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "N-glycosylation modulates ALT activity and serum levels.", "mechanism": "ALT elevation is a marker of liver cell damage from alcohol.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "N-glycosylation required for GGT enzymatic activity.", "mechanism": "GGT is increased in alcohol-induced liver injury.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Lipoprotein glycoproteins (ApoB, ApoA-I) mediate cholesterol transport.", "mechanism": "Alcohol consumption alters cholesterol metabolism, raising TC.", "protein": "TC", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "ApoB-100 glycosylation affects LDL receptor binding.", "mechanism": "Alcohol increases LDL, contributing to metabolic syndrome.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "ApoA-I glycosylation influences HDL function.", "mechanism": "Alcohol modulates HDL levels, impacting metabolic risk.", "protein": "HDL", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Alcoholic liver disease", "glycan_involvement": "Glycosylation status may affect serum enzyme ratios.", "mechanism": "Elevated AST/ALT ratio is characteristic of alcoholic liver injury.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "medium", "disease": "Hepatic encephalopathy", "glycan_involvement": "N-glycosylation essential for GGT activity.", "mechanism": "GGT elevation reflects liver dysfunction leading to encephalopathy.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "Altered glycosylation may affect AST clearance and neurotoxicity.", "mechanism": "Liver dysfunction (AST elevation) may contribute to cognitive decline via hepatic encephalopathy.", "protein": "AST", "relationship_type": "causal", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Kidney dysfunction", "glycan_involvement": "Not applicable (not a glycoprotein).", "mechanism": "Elevated creatinine indicates renal impairment in heavy drinkers.", "protein": "Cr", "relationship_type": "biomarker", "source_pmcid": "PMC12343226" }, { "confidence": "high", "disease": "Coronary artery calcification (CAC)", "glycan_involvement": "FTH is a glycoprotein, but specific glycan involvement in CAC not detailed.", "mechanism": "Elevated serum FTH predicts CAC progression in maintenance hemodialysis patients; associated with inflammation and oxidative stress.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12343228" }, { "confidence": "medium", "disease": "Vascular calcification (VC)", "glycan_involvement": "No direct evidence for glycan modification involvement in VC.", "mechanism": "Upregulated FTH expression in calcified aorta (mouse models); may promote VSMC osteogenic differentiation.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "causal", "source_pmcid": "PMC12343228" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "FTH upregulated in atherosclerotic calcification mouse models.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12343228" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Not specified.", "mechanism": "FTH upregulated in CKD-induced vascular calcification in mice.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12343228" }, { "confidence": "low", "disease": "Vascular calcification (VC)", "glycan_involvement": "Not specified.", "mechanism": "FTL expression increased in calcified vessels in animal models.", "protein": "Ferritin light chain (FTL)", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role ", "gene_name": "FTL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02792" }, "relationship_type": "associated", "source_pmcid": "PMC12343228" }, { "confidence": "low", "disease": "Vascular calcification (VC)", "glycan_involvement": "TFRC is a glycoprotein; glycosylation required for function, but not discussed in VC context.", "mechanism": "TFRC upregulated in calcified aorta in mouse models; involved in iron uptake.", "protein": "Transferrin receptor (TFRC)", "relationship_type": "associated", "source_pmcid": "PMC12343228" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Not specified.", "mechanism": "Elevated FTH linked to increased CVD risk in ESRD/MHD patients via VC.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12343228" }, { "confidence": "medium", "disease": "End-stage renal disease (ESRD)", "glycan_involvement": "Not specified.", "mechanism": "FTH levels reflect iron metabolism disturbances in ESRD, which are linked to VC/CAC.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12343228" }, { "confidence": "low", "disease": "Coronary artery calcification (CAC)", "glycan_involvement": "Not specified.", "mechanism": "Potential target for early intervention to slow CAC progression in MHD patients.", "protein": "Ferritin heavy chain (FTH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343228" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Not specified.", "mechanism": "TFRC upregulated in atherosclerotic calcification mouse models.", "protein": "Transferrin receptor (TFRC)", "relationship_type": "associated", "source_pmcid": "PMC12343228" }, { "confidence": "high", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "Glycosylation required for secretion and function; altered levels may reflect glycosylation changes.", "mechanism": "Downregulated in EVs; depletion impairs liver regeneration and tissue repair, contributing to increased parasite burden.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "high", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "Glycosylation modulates cell adhesion and pathogen interaction.", "mechanism": "Upregulated after Sb treatment; promotes parasite persistence by facilitating macrophage invasion.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "high", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "N-glycosylation critical for receptor binding and iron transport.", "mechanism": "Upregulated after Sb treatment; provides iron to parasites, supporting survival and proliferation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "N-glycosylation affects stability and activity.", "mechanism": "Downregulated in untreated, upregulated after Sb; higher levels associated with unresolved VL.", "protein": "Dipeptidyl peptidase-4", "protein_enriched": { "function": "Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding ", "gene_name": "Dpp4", "glycan_count": 3, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G28541PG", "G95177YH", "G49108TO" ], "uniprot_id": "P28843" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "high", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Downregulated in EVs; normally protects against oxidative stress and limits pathogen growth.", "protein": "Haemopexin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "Potential O-glycosylation modulates membrane localization.", "mechanism": "Downregulated in EVs; reduces lymphocyte activation, weakening immune response.", "protein": "Caveolin-1", "protein_enriched": { "function": "May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the re", "gene_name": "Cav1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49817" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "Not glycosylated.", "mechanism": "Upregulated in EVs; shifts to anti-inflammatory function, increasing Tregs and IL-10, promoting parasite persistence.", "protein": "High mobility group box 1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL under anti-TNF immunosuppression", "glycan_involvement": "Not glycosylated.", "mechanism": "Upregulated in EVs; may be hijacked by parasite to enhance antioxidant defense.", "protein": "Peroxiredoxin 2", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by ", "gene_name": "Prdx2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q61171" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL relapse", "glycan_involvement": "N-glycosylation affects trafficking and stability.", "mechanism": "Downregulated after Sb in anti-TNF; associated with cure in immunocompetent patients.", "protein": "Band 3 anion transport protein (Slc4a1)", "protein_enriched": { "function": "Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Component of the ankyrin-1 complex of the erythrocyte membrane; requir", "gene_name": "Slc4a1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G90659AW" ], "uniprot_id": "P04919" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343234" }, { "confidence": "medium", "disease": "VL relapse", "glycan_involvement": "Not glycosylated.", "mechanism": "Downregulated after Sb in anti-TNF; associated with cure in immunocompetent patients.", "protein": "Myosin-9", "protein_enriched": { "function": "Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By si", "gene_name": "MYH9", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR", "G70994MS" ], "uniprot_id": "P35579" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343234" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "CP is a glycoprotein; glycosylation affects its stability and half-life.", "mechanism": "ATP7B mutations reduce CP synthesis and secretion, leading to copper accumulation and hepatotoxicity.", "protein": "Ceruloplasmin (CP)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343240" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "CD147 is heavily glycosylated; glycosylation modulates its cell surface expression and function.", "mechanism": "Copper binds to CD147, promoting its self-aggregation and activation of MMPs, facilitating HCC cell migration and invasion.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12343240" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect copper binding.", "mechanism": "Albumin binds copper in circulation; D-penicillamine removes copper from albumin for excretion.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343240" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "Mucins are highly O-glycosylated; glycosylation is essential for copper binding.", "mechanism": "Mucins in intestinal mucus regulate copper absorption via copper-binding sites; altered mucin glycosylation may affect copper uptake.", "protein": "Mucins", "relationship_type": "causal/protective", "source_pmcid": "PMC12343240" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "CTR1 is N-glycosylated; glycosylation affects its membrane localization and copper transport.", "mechanism": "CTR1 overexpression increases copper uptake, promoting HCC cell proliferation and migration.", "protein": "CTR1 (SLC31A1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target/causal", "source_pmcid": "PMC12343240" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "COMMD3 is glycosylated; glycosylation may regulate its stability and function.", "mechanism": "COMMD3 overexpression increases VEGF and HIF-1\u03b1, promoting angiogenesis and tumor growth.", "protein": "COMMD3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12343240" }, { "confidence": "high", "disease": "Wilson disease", "glycan_involvement": "ATP7B is glycosylated; glycosylation may affect its trafficking and function.", "mechanism": "ATP7B mutations impair copper excretion and CP synthesis, causing copper overload in liver.", "protein": "ATP7B", "protein_enriched": { "function": "Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into t", "gene_name": "ATP7B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35670" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12343240" }, { "confidence": "medium", "disease": "Wilson disease", "glycan_involvement": "ZnT1 is glycosylated; glycosylation may affect transporter activity.", "mechanism": "ZnT1 transports copper and zinc; zinc therapy inhibits copper absorption via ZnT1.", "protein": "ZnT1 (SLC30A1)", "protein_enriched": { "function": "Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and tox", "gene_name": "SLC30A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "Q9Y6M5" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12343240" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "FDX1 is glycosylated; glycosylation may affect mitochondrial localization.", "mechanism": "FDX1 regulates cuproptosis; high FDX1 increases HCC cell susceptibility to copper-induced cell death.", "protein": "FDX1", "protein_enriched": { "function": "Essential for the synthesis of various steroid hormones (PubMed:20547883, PubMed:21636783). Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis (PubMed:20547883, PubMed:", "gene_name": "FDX1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10109" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12343240" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "PD-L1 is N-glycosylated; glycosylation stabilizes PD-L1 and modulates immune evasion.", "mechanism": "Copper ionophores upregulate PD-L1, promoting immunosuppression; combination with anti-PD-1 enhances antitumor immunity.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343240" }, { "confidence": "high", "disease": "Drug-resistant tumors", "glycan_involvement": "Glycosylation is essential for P-glycoprotein stability and function at the cell surface.", "mechanism": "P-glycoprotein mediates multidrug resistance by efflux of chemotherapeutics; PDT-generated ROS can inhibit its function, reducing resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and cell surface expression.", "mechanism": "EGFR is overexpressed in various cancers; antibody-conjugated photosensitizers target EGFR for selective PDT.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects HER2 dimerization and signaling.", "mechanism": "Anti-HER2 antibody-photosensitizer conjugates enable targeted PDT in HER2+ breast cancer.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for receptor function and ligand binding.", "mechanism": "Transferrin receptor is overexpressed in tumors; used for ligand-mediated delivery of photosensitizers.", "protein": "Transferrin receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates PD-1 stability and ligand interaction.", "mechanism": "PD-1 blockade with antibodies enhances immune response; combined with PDT for synergistic antitumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 inhibition (immune checkpoint) combined with PDT increases cytotoxic T cell infiltration and tumor regression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for CTLA4 surface expression.", "mechanism": "CTLA4 blockade with antibodies enhances antitumor immunity; synergistic with PDT-induced immunogenic cell death.", "protein": "CTLA4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma", "glycan_involvement": "Calreticulin is N-glycosylated, which may affect its immunogenicity.", "mechanism": "Surface-exposed calreticulin after PDT acts as an 'eat-me' signal, enhancing dendritic cell activation and antitumor immunity.", "protein": "Calreticulin", "protein_enriched": { "function": "", "gene_name": "CALR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7P0T861" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343272" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Folate receptor-targeted nanoparticles deliver photosensitizers selectively to tumors.", "protein": "Folate receptor", "protein_enriched": { "function": "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, P", "gene_name": "FOLR1", "glycan_count": 68, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G23294PN", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G59536GA", "G60177UT", "G62765YT", "G65184UU", "G66088HZ", "G66163OV", "G68490OW", "G70101JE", "G71051TA", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90382BL", "G92135MA", "G95133RI", "G98611JV", "G99668VU", "G92062TF", "G04657PL", "G05049YU", "G07755XJ", "G10819WX", "G11870QZ", "G13131HA", "G15169WU", "G15664MX", "G20210JR", "G23719VF", "G23984SE", "G31852PQ", "G36379GD", "G42124LM", "G45504EY", "G62894KT", "G70619PT", "G77547TA", "G84225JN", "G90659AW", "G95177YH", "G49108TO" ], "uniprot_id": "P15328" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "BCL-2 is a glycoprotein; glycosylation may affect its stability.", "mechanism": "PDT disrupts anti-apoptotic BCL-2, shifting balance toward apoptosis in cancer cells.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343272" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycation of hemoglobin is a non-enzymatic glycan modification linked to glucose levels.", "mechanism": "HbA1c reflects long-term glycemic dysregulation, a hallmark of insulin resistance.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycation status of hemoglobin correlates with disease severity.", "mechanism": "Elevated HbA1c is diagnostic for T2DM and reflects chronic hyperglycemia.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycation alters hemoglobin function and is linked to vascular damage.", "mechanism": "Higher HbA1c is associated with increased cardiovascular risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "high", "disease": "All-cause mortality", "glycan_involvement": "Degree of glycation reflects metabolic control and risk.", "mechanism": "Both high and excessively low HbA1c levels are associated with increased mortality risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "GLUT4 is glycosylated, which affects its trafficking and function.", "mechanism": "Estrogen regulates GLUT4; loss of estrogen reduces GLUT4 activity, promoting insulin resistance.", "protein": "Glucose transporter type 4 (GLUT4)", "relationship_type": "causal", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Albumin glycosylation status may influence vascular health.", "mechanism": "Lower albumin levels are associated with increased cardiovascular risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycation reflects poor glycemic control, increasing vascular complications.", "mechanism": "Lower eGDR (including higher HbA1c) is linked to increased stroke risk and post-stroke mortality.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycation status is indicative of metabolic dysfunction.", "mechanism": "HbA1c is a component of eGDR, which predicts metabolic syndrome prevalence.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Impaired fasting glucose", "glycan_involvement": "Glycation increases with chronic hyperglycemia.", "mechanism": "Higher HbA1c is associated with impaired fasting glucose.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "medium", "disease": "Impaired glucose tolerance", "glycan_involvement": "Glycation reflects glucose intolerance.", "mechanism": "Elevated HbA1c is linked to impaired glucose tolerance.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343283" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "High-mannose N-glycosylation is increased in tumor-derived EVs and glycoproteins in CRC plasma.", "mechanism": "Elevated levels of HM N-glycosylated glycoproteins and EVs in plasma are associated with early-stage CRC and can be captured by OAA1 lectin for diagnostic purposes.", "protein": "High-mannose N-glycosylated glycoproteins (general, including EV membrane proteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Contains high-mannose N-glycans recognized by OAA1.", "mechanism": "Thyroglobulin with HM N-glycans is bound by OAA1, demonstrating the lectin's specificity for HM N-glycosylated proteins in CRC plasma.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "EV membrane proteins are high-mannose N-glycosylated in CRC.", "mechanism": "CD81-positive EVs with HM N-glycans are increased in CRC plasma and can be selectively captured by OAA1 columns.", "protein": "CD81 (EV marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "High-mannose N-glycosylation detected in CRC plasma.", "mechanism": "Apolipoprotein B is HM N-glycosylated and present in OAA1-captured plasma fractions, indicating altered glycosylation in CRC.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "High-mannose N-glycosylation detected in CRC plasma.", "mechanism": "Complement C3 is HM N-glycosylated and enriched in OAA1-captured plasma from CRC patients.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "High-mannose N-glycosylation detected in CRC plasma.", "mechanism": "Alpha-2-macroglobulin is HM N-glycosylated and present in OAA1-captured fractions from CRC plasma.", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "High-mannose N-glycosylation is increased in ovarian cancer.", "mechanism": "Elevated HM N-glycosylation observed in ovarian cancer tissues.", "protein": "High-mannose N-glycosylated glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "High-mannose N-glycosylation is increased in breast cancer.", "mechanism": "Elevated HM N-glycosylation observed in breast cancer tissues.", "protein": "High-mannose N-glycosylated glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "High-mannose N-glycosylation is increased in prostate cancer.", "mechanism": "Elevated HM N-glycosylation observed in prostate cancer tissues.", "protein": "High-mannose N-glycosylated glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "High-mannose N-glycosylation changes contribute to disease onset.", "mechanism": "Altered glycosylation, including HM N-glycans, is implicated in Alzheimer's disease pathology.", "protein": "High-mannose N-glycosylated glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC12343284" }, { "confidence": "high", "disease": "Non-Small Cell Lung Cancer (NSCLC)", "glycan_involvement": "Folate receptor is a glycoprotein; glycosylation affects ligand binding and targeting.", "mechanism": "Folate-conjugated zein nanoparticles target folate receptor-overexpressing NSCLC cells for enhanced drug delivery.", "protein": "Folate Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "medium", "disease": "Leukaemia", "glycan_involvement": "Zein can be functionalized with glycan-binding ligands for cell targeting.", "mechanism": "Zein nanoparticles enable targeted delivery of chemotherapeutics to leukaemia cells, reducing systemic toxicity.", "protein": "Zein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "PTEN is glycosylated; glycosylation may affect stability and delivery.", "mechanism": "Zein nanoparticles deliver PTEN gene to HCC cells, restoring tumor suppressor function and inhibiting proliferation.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "TRAIL is a glycoprotein; glycosylation modulates receptor interaction.", "mechanism": "Co-delivery of TRAIL with PTEN via zein nanoparticles enhances apoptosis in HCC cells.", "protein": "TRAIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "low", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "VEGF glycosylation affects secretion and receptor binding.", "mechanism": "Zein nanoparticle-mediated gene therapy upregulates VEGF mRNA as part of apoptosis and tumor suppression.", "protein": "VEGF", "relationship_type": "biomarker", "source_pmcid": "PMC12343330" }, { "confidence": "low", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "MMP-2 is glycosylated; glycosylation regulates activity.", "mechanism": "Zein nanoparticle therapy modulates MMP-2 expression, impacting tumor invasion.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343330" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "CD44 is a glycoprotein; glycosylation modulates HA binding.", "mechanism": "Zein/HA nanoparticles target CD44-overexpressing breast cancer cells for drug delivery.", "protein": "Hyaluronic Acid Receptor (CD44)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "low", "disease": "Colorectal Cancer", "glycan_involvement": "Chondroitin sulphate is a glycosaminoglycan; glycosylation is essential for function.", "mechanism": "Zein/CS nanoparticles exploit proteoglycan interactions for targeted delivery in colorectal cancer.", "protein": "Chondroitin Sulphate Proteoglycans", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "medium", "disease": "Tumor Microenvironment Disorders", "glycan_involvement": "Integrins are glycoproteins; glycosylation affects ligand binding.", "mechanism": "Zein nanoparticles functionalized with RGD peptides target integrins in tumor vasculature.", "protein": "RGD-binding Integrins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "low", "disease": "Liver Cancer", "glycan_involvement": "Receptor glycosylation mediates ligand recognition.", "mechanism": "Zein nanoparticles with lactobionic acid target liver-specific glycoprotein receptors for drug delivery.", "protein": "Lactobionic Acid Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343330" }, { "confidence": "high", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "Bcl11b is a glycoprotein; glycosylation may affect stability and localization, but not directly studied here.", "mechanism": "Upregulation of Bcl11b in macrophages promotes M1 polarization and increases pro-inflammatory cytokine production, exacerbating lung injury.", "protein": "Bcl11b", "relationship_type": "causal", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "miR-17-5p is transported in exosomes, which are enriched in glycoproteins (CD63, CD81) facilitating delivery.", "mechanism": "Downregulation of exosomal miR-17-5p in sepsis leads to increased Bcl11b, M1 polarization, and inflammation; restoration of miR-17-5p is protective.", "protein": "miR-17-5p (exosomal)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Heavily N-glycosylated; glycosylation critical for exosome formation and function.", "mechanism": "CD63 is an exosomal marker used to identify plasma exosomes involved in immune modulation during sepsis.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation important for exosome targeting and stability.", "mechanism": "CD81 is an exosomal marker used to identify plasma exosomes involved in immune modulation during sepsis.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "N-glycosylation modulates ligand binding and immune signaling.", "mechanism": "CD86 upregulation marks M1 macrophage polarization, associated with increased inflammation in sepsis-induced ALI.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "N-glycosylation required for ligand recognition and endocytosis.", "mechanism": "CD206 upregulation marks M2 macrophage polarization, associated with anti-inflammatory response and tissue repair.", "protein": "CD206 (MRC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12343337" }, { "confidence": "medium", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "Possible N-glycosylation affects enzyme stability.", "mechanism": "iNOS upregulation in M1 macrophages leads to increased nitric oxide and tissue damage in ALI.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343337" }, { "confidence": "medium", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "Possible N-glycosylation affects enzyme activity.", "mechanism": "Arg-1 upregulation in M2 macrophages is associated with anti-inflammatory effects and tissue repair.", "protein": "Arg-1", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "O-glycosylation modulates secretion and receptor interaction.", "mechanism": "TNF-\u03b1 is a key pro-inflammatory cytokine elevated in M1 macrophage polarization, driving lung injury.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343337" }, { "confidence": "medium", "disease": "Sepsis-induced Acute Lung Injury (ALI)", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "TGF-\u03b2 is upregulated in M2 macrophages, promoting resolution of inflammation and tissue repair.", "protein": "TGF-\u03b2", "relationship_type": "protective", "source_pmcid": "PMC12343337" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Mcl-1 is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Mcl-1 overexpression promotes AML cell survival and resistance to apoptosis.", "protein": "Mcl-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343358" }, { "confidence": "high", "disease": "Relapsed/Refractory AML", "glycan_involvement": "Glycosylation may modulate Mcl-1 turnover and apoptotic signaling.", "mechanism": "Increased Mcl-1 expression is associated with resistance to venetoclax and disease progression.", "protein": "Mcl-1", "relationship_type": "causal", "source_pmcid": "PMC12343358" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Bcl-2 is a glycoprotein; glycosylation may influence its antiapoptotic function.", "mechanism": "Bcl-2 overexpression is linked to chemoresistance; targeted by venetoclax.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Chemoresistant AML", "glycan_involvement": "Glycosylation status may affect Mcl-1 detection and function.", "mechanism": "High Mcl-1 levels predict poor response to venetoclax and chemotherapy.", "protein": "Mcl-1", "relationship_type": "biomarker", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "RNAPII is a glycoprotein; glycosylation may affect nuclear localization and stability.", "mechanism": "Phosphorylation of RNAPII Ser2 by CDK9 supports transcription of survival genes (e.g., Mcl-1).", "protein": "RNA polymerase II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343358" }, { "confidence": "high", "disease": "Chemoresistant AML", "glycan_involvement": "N-glycosylation is essential for P-gp trafficking and function.", "mechanism": "P-gp mediates drug efflux, contributing to multidrug resistance in AML.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Cardiotoxicity", "glycan_involvement": "Glycosylation may influence Mcl-1 tissue distribution.", "mechanism": "On-target inhibition of Mcl-1 in cardiac tissue leads to cardiotoxicity with direct Mcl-1 inhibitors.", "protein": "Mcl-1", "relationship_type": "causal", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation may affect Mcl-1 detection in assays.", "mechanism": "Dynamic changes in Mcl-1 levels during therapy may predict response to CDK9 inhibition.", "protein": "Mcl-1", "relationship_type": "biomarker", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Chemoresistant AML", "glycan_involvement": "Glycosylation may modulate Bcl-2 function.", "mechanism": "Bcl-2 overexpression confers resistance to apoptosis-inducing therapies.", "protein": "Bcl-2", "relationship_type": "causal", "source_pmcid": "PMC12343358" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "N-glycosylation critical for P-gp drug transport activity.", "mechanism": "P-gp inhibition may enhance efficacy of chemotherapeutics in AML.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343358" }, { "confidence": "high", "disease": "Heat stress-induced intestinal barrier dysfunction", "glycan_involvement": "ZO-1 is a glycoprotein; glycosylation stabilizes its membrane localization and function.", "mechanism": "Upregulation of ZO-1 strengthens tight junctions, restoring barrier integrity under heat stress.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12343427" }, { "confidence": "high", "disease": "Heat stress-induced intestinal barrier dysfunction", "glycan_involvement": "Occludin glycosylation is essential for tight junction assembly.", "mechanism": "Increased Occludin expression improves tight junctions, reducing gut permeability.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12343427" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may affect ACSL1 stability and activity.", "mechanism": "Upregulation of ACSL1 promotes fatty acid \u03b2-oxidation, reducing hepatic lipid accumulation.", "protein": "ACSL1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343427" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "SCD glycosylation influences its enzymatic activity.", "mechanism": "Downregulation of SCD reduces fatty acid synthesis, limiting steatosis.", "protein": "SCD", "relationship_type": "causal", "source_pmcid": "PMC12343427" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may regulate CPT1A membrane targeting.", "mechanism": "Upregulation enhances mitochondrial fatty acid oxidation, protecting against NAFLD.", "protein": "CPT1A", "protein_enriched": { "function": "Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxid", "gene_name": "CPT1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P50416" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343427" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Sphingomyelin is a glycosphingolipid; glycan moieties affect membrane stability.", "mechanism": "Elevated SM correlates with improved liver health and reduced steatosis.", "protein": "SM (d18:1/22:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12343427" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "LPC is a glycolipid; glycan structure influences signaling.", "mechanism": "Increased LPC (32:0) reflects enhanced antioxidant capacity and lipid transport.", "protein": "LPC (32:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12343427" }, { "confidence": "low", "disease": "Lipid dysregulation", "glycan_involvement": "Glycosylation modulates FABP3 function.", "mechanism": "Downregulation of FABP3 is associated with improved lipid metabolism.", "protein": "FABP3", "relationship_type": "causal", "source_pmcid": "PMC12343427" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "PLIN1 glycosylation affects lipid droplet association.", "mechanism": "Upregulation of PLIN1 stabilizes lipid droplets, reducing liver injury.", "protein": "PLIN1", "relationship_type": "protective", "source_pmcid": "PMC12343427" }, { "confidence": "medium", "disease": "Metabolic dysfunction", "glycan_involvement": "LPL glycosylation is critical for enzymatic activity.", "mechanism": "Upregulation of LPL improves plasma lipid profiles and metabolic health.", "protein": "LPL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343427" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates IL-6 secretion and stability.", "mechanism": "Elevated IL-6 reflects cytokine storm and systemic inflammation in severe COVID-19.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "high", "disease": "Acute cardiac injury", "glycan_involvement": "Glycosylation affects troponin I stability and clearance.", "mechanism": "Elevated troponin I indicates myocardial injury, associated with increased mortality in old-old COVID-19 patients.", "protein": "Cardiac troponin I", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "high", "disease": "Malnutrition", "glycan_involvement": "N-glycosylation influences albumin half-life and function.", "mechanism": "Low serum albumin is associated with poor prognosis and higher mortality in old-old COVID-19 patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "D-dimer is a glycopeptide fragment; glycosylation affects its detection and clearance.", "mechanism": "Elevated D-dimer indicates fibrinolysis and is associated with increased mortality in elderly COVID-19 patients.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "medium", "disease": "Bacterial infection", "glycan_involvement": "Glycosylation modulates procalcitonin secretion.", "mechanism": "Elevated procalcitonin suggests bacterial co-infection, worsening COVID-19 prognosis.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation is critical for fibrinogen function and clot formation.", "mechanism": "Altered fibrinogen levels reflect coagulation abnormalities in severe COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "medium", "disease": "Acute cardiac injury", "glycan_involvement": "Glycosylation affects BNP stability and bioactivity.", "mechanism": "Elevated BNP indicates cardiac stress and is associated with poor outcomes in old-old COVID-19 patients.", "protein": "Brain Natriuretic Peptide (BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Surface glycosylation modulates immune cell trafficking and activation.", "mechanism": "Altered WBC counts and activation reflect immune dysregulation in severe COVID-19.", "protein": "White blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "medium", "disease": "Bacterial infection", "glycan_involvement": "Glycosylation regulates neutrophil adhesion and migration.", "mechanism": "Elevated neutrophil counts indicate secondary infection and worse prognosis.", "protein": "Neutrophil surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12343559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding and infectivity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; increased expression in old-old may increase susceptibility.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343559" }, { "confidence": "high", "disease": "Kidney fibrosis", "glycan_involvement": "Glycosylation modulates ligand binding and cell interactions.", "mechanism": "CD44 mediates cell adhesion and migration, promoting renal fibrosis and correlating with proteinuria and disease severity.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343563" }, { "confidence": "high", "disease": "Kidney fibrosis", "glycan_involvement": "Glycosylation affects matrix assembly and cell adhesion.", "mechanism": "FN1 overexpression leads to excessive extracellular matrix accumulation and fibrosis.", "protein": "FN1", "relationship_type": "causal", "source_pmcid": "PMC12343563" }, { "confidence": "medium", "disease": "Organismal aging", "glycan_involvement": "Glycosylation influences immune cell interactions.", "mechanism": "CD4 overexpression is associated with immune dysregulation and accelerated aging.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343563" }, { "confidence": "medium", "disease": "Organismal aging", "glycan_involvement": "N-glycosylation regulates receptor function and ligand binding.", "mechanism": "EGFR signaling declines with age, affecting stress response and cell proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343563" }, { "confidence": "medium", "disease": "Autoimmunity", "glycan_involvement": "Glycosylation impacts phosphatase activity and cell signaling.", "mechanism": "CD45 modulates T-cell activation; inhibitors suppress immune responses and may treat autoimmunity.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343563" }, { "confidence": "medium", "disease": "Renal glomerulopathies", "glycan_involvement": "Glycosylation affects macrophage function and antigen presentation.", "mechanism": "CD68 marks macrophage infiltration in kidney disease and is a potential drug target for ACE inhibitors.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343563" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates enzyme activity and inhibitor binding.", "mechanism": "ACE regulates blood pressure; inhibition reduces hypertension and protects kidneys.", "protein": "ACE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343563" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation influences receptor localization and signaling.", "mechanism": "AGTR1 mediates angiotensin II effects; antagonists lower blood pressure.", "protein": "AGTR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343563" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation affects lipid transport and cell interactions.", "mechanism": "APOE mutations contribute to mesangial expansion and kidney dysfunction.", "protein": "APOE", "relationship_type": "causal", "source_pmcid": "PMC12343563" }, { "confidence": "high", "disease": "Cancer (various)", "glycan_involvement": "Glycosylation modulates tumor cell adhesion and migration.", "mechanism": "CD44 promotes tumor growth and metastasis; peptide inhibitors block its function.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343563" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Polysaccharide structure may influence receptor binding and lipid metabolism.", "mechanism": "Lipid-lowering effect via modulation of lipid metabolism and AMPK pathway activation.", "protein": "Monascus purpureus Went polysaccharide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Fatty liver", "glycan_involvement": "Glycosylation may affect antioxidant activity and cellular uptake.", "mechanism": "Regulates lipid metabolism and protects liver cells from oxidative damage.", "protein": "Extracellular polysaccharide (EPS)", "relationship_type": "protective", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Pigment glycosylation may modulate bioactivity and stability.", "mechanism": "Regulates blood lipids and protects liver via AMPK pathway activation.", "protein": "Monascus pigment (yellow pigment)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may affect cell targeting and uptake.", "mechanism": "Promotes apoptosis of gastric cancer cells without affecting normal cells.", "protein": "Monascus pigment (monascorubramine)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "No direct glycosylation, but may interact with glycoprotein receptors.", "mechanism": "Inhibits cholesterol synthesis, lowering LDL and total cholesterol.", "protein": "Lovastatin (monacolin K)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Tumor growth (general)", "glycan_involvement": "Polysaccharide structure may affect immune modulation and tumor cell recognition.", "mechanism": "Inhibits tumor cell proliferation and induces apoptosis.", "protein": "Monascus purpureus Went polysaccharide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation enhances antioxidant properties.", "mechanism": "Scavenges free radicals, reduces ALT/AST, protects liver function.", "protein": "Extracellular polysaccharide (EPS)", "relationship_type": "protective", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "No direct glycosylation, but may interact with glycoprotein transporters.", "mechanism": "Reduces blood glucose levels and improves renal function.", "protein": "Ergosterol", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Reduces inflammatory markers (TNF-\u03b1, CRP) and oxidative stress.", "protein": "Monascus purpureus Went polysaccharide", "relationship_type": "protective", "source_pmcid": "PMC12343590" }, { "confidence": "medium", "disease": "Dermatitis", "glycan_involvement": "Glycosylation may affect skin cell interaction.", "mechanism": "Reduces inflammation via antioxidant and anti-inflammatory pathways.", "protein": "Monascus purpureus Went polysaccharide", "relationship_type": "protective", "source_pmcid": "PMC12343590" }, { "confidence": "high", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and function.", "mechanism": "Lower serum albumin is associated with increased CHD risk due to reduced antioxidant and anti-inflammatory capacity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343592" }, { "confidence": "high", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "HDL-c contains glycoproteins (e.g., ApoA-1) whose glycosylation modulates function.", "mechanism": "Low HDL-c is a risk factor for CHD; HDL-c mediates reverse cholesterol transport and inhibits LDL oxidation.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Atherosclerosis (AS)", "glycan_involvement": "Glycosylation influences albumin's antioxidant activity.", "mechanism": "Albumin's antioxidant and anti-inflammatory properties protect against vascular inflammation and plaque instability.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Atherosclerosis (AS)", "glycan_involvement": "Glycosylation of HDL-associated proteins affects cholesterol efflux.", "mechanism": "HDL-c prevents lipid deposition and promotes cholesterol efflux from arterial walls.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "ApoA-1 glycosylation modulates HDL particle stability and function.", "mechanism": "ApoA-1 is essential for HDL function; displacement by SAA during inflammation impairs cholesterol efflux.", "protein": "Apolipoprotein A-1 (ApoA-1)", "relationship_type": "protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "SAA is glycosylated; glycosylation may affect its interaction with HDL.", "mechanism": "SAA displaces ApoA-1 from HDL during inflammation, reducing HDL's anti-atherosclerotic capacity.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "causal", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Major adverse cardiovascular events (MACE)", "glycan_involvement": "Glycosylation status may influence albumin's protective effects.", "mechanism": "Lower albumin predicts higher risk of MACE and in-hospital mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "HDL glycoprotein composition affects vascular protection.", "mechanism": "Higher HDL-c levels reduce risk of ischemic and hemorrhagic stroke.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "protective", "source_pmcid": "PMC12343592" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation may modulate albumin's vascular effects.", "mechanism": "Low albumin is associated with increased stroke risk due to impaired vascular protection.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343592" }, { "confidence": "medium", "disease": "Atherosclerosis (AS)", "glycan_involvement": "Glycosylation affects ApoA-1's interaction with lipids and arterial walls.", "mechanism": "ApoA-1 facilitates cholesterol efflux and inhibits atherogenesis.", "protein": "Apolipoprotein A-1 (ApoA-1)", "relationship_type": "protective", "source_pmcid": "PMC12343592" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation required for cell surface expression and stability.", "mechanism": "Highly expressed in injured proximal tubular cells; correlates with inflammation and fibrosis severity.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Secreted glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Secreted by stressed tubular epithelial cells; urinary levels correlate with severity of tubular atrophy and interstitial fibrosis.", "protein": "DKK-3", "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Glycosylation modulates cell adhesion and immune interactions.", "mechanism": "Upregulated in fibrotic tissue; serum levels correlate with CKD risk and disease activity.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Released during kidney injury; urinary levels associate with CKD risk and proteinuria.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Glycosylation influences secretion and enzymatic activity.", "mechanism": "Elevated in blood/urine; predicts CKD progression and correlates with renal fibrosis.", "protein": "MMP-7", "protein_enriched": { "function": "Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase", "gene_name": "MMP7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09237" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Central mediator of fibrosis; induces fibroblast activation and ECM deposition.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12343605" }, { "confidence": "high", "disease": "CKD", "glycan_involvement": "Glycosylation affects secretion and chemokine activity.", "mechanism": "Promotes inflammatory cell recruitment; urinary levels associate with CKD progression and fibrosis.", "protein": "MCP-1", "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation modulates secretion and function.", "mechanism": "Upregulated in CKD; associated with fibrosis severity.", "protein": "ANGPTL4", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697", "gene_name": "ANGPTL4", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G14994KB", "G22310AV", "G23863VK", "G27058EU", "G31852PQ", "G37412TK", "G37881RL", "G41071NU", "G45395BF", "G45495MK", "G48414YA", "G52527GH", "G56784JY", "G57818FI", "G62461SM", "G62765YT", "G71146HJ", "G75983OB", "G80920RR", "G84452RH", "G90659AW", "G43417UB", "G53434XO", "G88713AC" ], "uniprot_id": "Q9BY76" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "Glycosylation required for secretion and ECM binding.", "mechanism": "Elevated in CKD; associated with risk of kidney failure replacement therapy.", "protein": "YKL-40", "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "medium", "disease": "CKD", "glycan_involvement": "Glycosylation may affect stability and chaperone function.", "mechanism": "Serum levels elevated in CKD; correlate with clinical markers of disease.", "protein": "HSP90B2", "relationship_type": "biomarker", "source_pmcid": "PMC12343605" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Serum albumin is N-glycosylated; glycosylation status may affect stability and half-life, but not directly discussed in this article.", "mechanism": "Low serum albumin is associated with increased risk of sarcopenia, reflecting poor nutritional status and inflammation.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12343613" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "Glycosylation may modulate albumin function in inflammation, but not directly discussed in this article.", "mechanism": "Low serum albumin is a marker of poor prognosis and nutritional risk in COPD patients.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12343613" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoAI) whose glycosylation affects function.", "mechanism": "Low HDL-C is associated with increased risk of T2DM; HDL-C participates in reverse cholesterol transport and anti-inflammatory processes.", "protein": "HDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "ApoAI glycosylation modulates HDL metabolism and clearance.", "mechanism": "Reduced ApoAI (on HDL) clearance in T2DM due to altered glycosylation; impacts HDL function.", "protein": "ApoAI", "relationship_type": "biomarker", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of LDL apolipoproteins affects receptor binding and clearance.", "mechanism": "Elevated LDL-C, especially small dense LDL (sdLDL), promotes atherogenesis.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "VLDL contains glycoproteins; glycosylation affects secretion and metabolism.", "mechanism": "Increased VLDL synthesis in insulin resistance leads to hypertriglyceridemia and T2DM risk.", "protein": "VLDL", "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "CETP is a glycoprotein; glycosylation may influence activity.", "mechanism": "CETP mediates transfer of triglycerides to HDL and LDL, altering lipid profiles and increasing CVD risk.", "protein": "CETP", "protein_enriched": { "function": "Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed ", "gene_name": "CXCL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19876" }, "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "IRS-1 is glycosylated; glycosylation may modulate signaling.", "mechanism": "IRS-1 phosphorylation impairs insulin signaling, leading to insulin resistance.", "protein": "IRS-1", "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "TNF-\u03b1 induces serine phosphorylation of IRS-1, impairing insulin signaling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "IL-6 glycosylation affects receptor binding and bioactivity.", "mechanism": "IL-6 promotes inflammation and impairs insulin signaling.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-atherogenic functions.", "mechanism": "HDL-C removes cholesterol from arteries, reducing atherosclerosis risk.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12343622" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "ApoAI glycosylation influences HDL stability and function.", "mechanism": "ApoAI is essential for HDL function and reverse cholesterol transport.", "protein": "ApoAI", "relationship_type": "protective", "source_pmcid": "PMC12343622" }, { "confidence": "high", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Glycosylation may affect SOCS3 stability and secretion, but not directly discussed.", "mechanism": "Upregulated in SLI; regulates inflammation and macrophage polarization, inhibits IL-6/JAK/STAT signaling, associated with liver repair.", "protein": "SOCS3", "relationship_type": "biomarker", "source_pmcid": "PMC12343667" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Not directly discussed.", "mechanism": "SOCS3 expression is significantly increased in early septic shock, indicating acute inflammatory response.", "protein": "SOCS3", "relationship_type": "biomarker", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Glycosylation modulates integrin function and cell adhesion.", "mechanism": "Mediates monocyte/macrophage adherence to hepatic sinusoids, promoting innate immune activation and inflammation.", "protein": "ITGAM (CD11b)", "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Heavily glycosylated; glycan modifications regulate ligand binding and migration.", "mechanism": "Facilitates immune cell adhesion and migration in liver during sepsis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Glycosylation affects secretion and activity of MMP9.", "mechanism": "Activates \u03b3\u03b4 T-cell/neutrophil axis, triggers neutrophil infiltration and NETosis, exacerbating liver injury.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "N-glycosylation critical for CD74 trafficking and function.", "mechanism": "Regulates dendritic cell and T-cell activation, disrupts antigen presentation, contributes to immune dysregulation.", "protein": "CD74", "protein_enriched": { "function": "Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex fro", "gene_name": "CD74", "glycan_count": 90, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G04657PL", "G05724UK", "G08290VR", "G08918WF", "G14972EH", "G20528HD", "G20706XG", "G22310AV", "G23505EP", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31852PQ", "G37509XX", "G39188ZX", "G40206WX", "G40834TG", "G40926MX", "G41247ZX", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G45395BF", "G45526EA", "G46503DX", "G46691LC", "G49642SA", "G50282JC", "G51653BI", "G54010QB", "G57776ZS", "G58954YZ", "G59324HL", "G59626AS", "G60033FS", "G62765YT", "G64409MC", "G64527OM", "G70101JE", "G73968GN", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G83646BJ", "G84452RH", "G84862VB", "G87123QX", "G88891KO", "G90575OW", "G92135MA", "G93718GY", "G95865ZB", "G98611JV", "G02886BB", "G07246CJ", "G15664MX", "G25079LO", "G25451PN", "G28541PG", "G35253PZ", "G36442WJ", "G39446WN", "G41071NU", "G45495MK", "G49018RC", "G59924QI", "G68490OW", "G70441OD", "G70619PT", "G71146HJ", "G72747WU", "G75983OB", "G87661QW", "G90659AW", "G96430BV", "G57321FI", "G29931IJ", "G43417UB", "G02815KT", "G05049YU", "G23719VF", "G75418YA", "G49108TO" ], "uniprot_id": "P04233" }, "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "Involved in dendritic cell and T-cell hyperactivation, leading to adaptive immune failure.", "protein": "FCER1G", "protein_enriched": { "function": "Adapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. As a component of the high-affinity immunoglobulin ", "gene_name": "FCER1G", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30273" }, "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Possible glycosylation affects stability; not directly discussed.", "mechanism": "Promotes inflammatory signaling and monocyte activation.", "protein": "MAPK14", "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Not directly discussed.", "mechanism": "Enriches apoptosis/angiogenesis pathways, mediates inflammasome activation and pyroptosis.", "protein": "NLRC4", "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "medium", "disease": "Sepsis-induced liver injury (SLI)", "glycan_involvement": "Glycosylation may affect secretion; not directly discussed.", "mechanism": "Correlates with monocyte and neutrophil activation, amplifies inflammatory response.", "protein": "S100A12", "protein_enriched": { "function": "Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does n", "gene_name": "S100A13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99584" }, "relationship_type": "causal", "source_pmcid": "PMC12343667" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "GP130 is a glycoprotein; glycosylation is required for proper folding, stability, and receptor function.", "mechanism": "GP130 forms a receptor complex with IL-6 and IL-6R, mediating downstream JAK/STAT3 and PI3K/AKT signaling essential for auricular cartilage development and regeneration.", "protein": "Glycoprotein 130 (GP130/IL6ST)", "relationship_type": "causal", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation may affect secretion and stability but not specifically addressed in this study.", "mechanism": "IL-6 is significantly downregulated in microtia cartilage; its expression level correlates inversely with disease severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "Glycosylation may influence IL-6 bioactivity; not directly studied here.", "mechanism": "IL-6 supplementation (via AAV gene therapy) in pregnant mice prevents microtia phenotype and restores cartilage development.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "IL-6R is a glycoprotein; glycosylation is important for receptor function.", "mechanism": "IL-6R, as part of the IL-6/GP130 complex, is necessary for IL-6 signaling in chondrocytes and stem cells; disruption impairs cartilage development.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "causal", "source_pmcid": "PMC12343669" }, { "confidence": "medium", "disease": "Microtia", "glycan_involvement": "Glycosylation required for cell surface expression and function.", "mechanism": "GP130 is co-expressed with IL-6 and IL-6R in affected tissues; its presence marks active IL-6 signaling.", "protein": "Glycoprotein 130 (GP130/IL6ST)", "relationship_type": "biomarker", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "Glycosylation may modulate IL-6 secretion and receptor interaction.", "mechanism": "IL-6 promotes proliferation, migration, and chondrogenic differentiation of primary chondrocytes and stem cells, supporting cartilage regeneration.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "protective", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "Not directly addressed.", "mechanism": "IL-6 deficiency leads to impaired intercellular communication between stem cells and chondrocytes, resulting in auricular cartilage underdevelopment.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12343669" }, { "confidence": "medium", "disease": "Microtia", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Blocking IL-6R with tocilizumab inhibits IL-6-mediated effects on cell proliferation and migration, confirming its role in disease mechanism.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343669" }, { "confidence": "medium", "disease": "Microtia", "glycan_involvement": "Glycosylation necessary for receptor complex formation.", "mechanism": "Targeting GP130 could modulate IL-6 signaling and affect cartilage development.", "protein": "Glycoprotein 130 (GP130/IL6ST)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Microtia", "glycan_involvement": "Not directly addressed.", "mechanism": "IL-6 signaling is required for activation of JAK/STAT3 and PI3K/AKT pathways, which are essential for ear cartilage morphogenesis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12343669" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and immune recognition.", "mechanism": "CRP levels rise in response to systemic inflammation and infection.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343738" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-6 glycosylation modulates receptor binding and activity.", "mechanism": "IL-6 is released early in sepsis, driving cytokine storm and inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12343738" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and bioactivity.", "mechanism": "TNF-\u03b1 initiates cytokine cascade, leading to systemic inflammation.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation of component proteins may regulate assembly and activation.", "mechanism": "Activation leads to IL-1\u03b2 release and inflammation.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Wound healing impairment", "glycan_involvement": "MMP glycosylation influences secretion and substrate specificity.", "mechanism": "Upregulated MMPs degrade extracellular matrix, impairing healing.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "causal", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Cardiac surgery complications", "glycan_involvement": "Glycosylation affects NT-proBNP clearance and detection.", "mechanism": "Elevated NT-proBNP indicates cardiac stress and predicts complications.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Albumin glycosylation may affect vascular permeability and antioxidant function.", "mechanism": "Low albumin is associated with poor prognosis in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Organ dysfunction", "glycan_involvement": "N-glycosylation modulates prothrombin activation and stability.", "mechanism": "Altered prothrombin levels reflect coagulation dysfunction in sepsis.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Organ dysfunction", "glycan_involvement": "Glycosylation affects fibrinogen polymerization and clot formation.", "mechanism": "Fibrinogen is consumed during systemic inflammation, indicating coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343738" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "ACE glycosylation impacts enzymatic activity and inhibitor binding.", "mechanism": "ACE regulates blood pressure; inhibitors used perioperatively.", "protein": "Angiotensin converting enzyme (ACE)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12343738" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Akt1 is targeted by glycosylated flavonoids (kaempferol glycosides) with enhanced inhibitory activity.", "mechanism": "Akt1 hyperactivation promotes proliferation, survival, and drug resistance in breast cancer.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylated flavonoids predicted to inhibit Akt1.", "mechanism": "Akt1 activation drives tumor progression and resistance.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Flavonoid glycosides (e.g., Rutin) modulate Akt1 activity.", "mechanism": "Akt1 promotes tumor initiation, progression, and metastasis.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylated flavonoids act as inhibitors.", "mechanism": "Akt1 implicated in tumor progression.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Glycosylated flavonoids predicted to inhibit Akt1.", "mechanism": "Akt1 activity linked to aggressive and metastatic features.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "high", "disease": "Therapy-resistant cancers", "glycan_involvement": "Kaempferol glycosides show high affinity for Akt1.", "mechanism": "Akt1 hyperactivation contributes to resistance; inhibition may overcome resistance.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Fibrotic lung disease", "glycan_involvement": "Baicalin (glycosylated flavonoid) inhibits Akt pathway.", "mechanism": "PI3K/Akt pathway promotes fibroblast proliferation and fibrosis.", "protein": "Akt1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343748" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Indirect; glycosylated flavonoids inhibit Akt1, leading to FOXO3 activation.", "mechanism": "Akt1 inhibits FOXO3 by phosphorylation; inhibition of Akt1 upregulates FOXO3, promoting apoptosis.", "protein": "FOXO3", "protein_enriched": { "function": "Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed", "gene_name": "FOXO3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G81295CK" ], "uniprot_id": "O43524" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Gastric ulceration", "glycan_involvement": "Amentoflavone is a biflavonoid glycoside.", "mechanism": "Amentoflavone modulates AMPK/mTOR pathway, reducing ulcer severity.", "protein": "Akt1", "relationship_type": "protective", "source_pmcid": "PMC12343748" }, { "confidence": "medium", "disease": "Cardiac hypoxia-reoxygenation injury", "glycan_involvement": "Orientin is a C-glycosylated flavone.", "mechanism": "Orientin modulates PI3K/Akt/mTOR pathway, promoting autophagy and cardioprotection.", "protein": "Akt1", "relationship_type": "protective", "source_pmcid": "PMC12343748" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "CTSD is a glycoprotein; glycosylation is required for lysosomal targeting and stability.", "mechanism": "CTSD is highly expressed in AML and correlates with poor prognosis.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation affects CTSD trafficking and function.", "mechanism": "CTSD inhibition (genetic or pharmacologic) suppresses AML cell proliferation and induces apoptosis.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Monocytic AML (AML-M4/M5)", "glycan_involvement": "Glycosylation status may influence CTSD levels in these subtypes.", "mechanism": "CTSD is especially elevated in monocytic AML subtypes, associated with worse outcomes.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "BCL2 is glycosylated, which may affect its stability and interactions.", "mechanism": "BCL2 is stabilized by CTSD, promoting AML cell survival; its degradation induces apoptosis.", "protein": "BCL2", "relationship_type": "causal", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "BCL-XL glycosylation may modulate its anti-apoptotic function.", "mechanism": "BCL-XL is stabilized by CTSD; CTSD inhibition leads to its ubiquitin-mediated degradation and apoptosis.", "protein": "BCL-XL (BCL2L1)", "relationship_type": "causal", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "MCL1 glycosylation may influence its stability.", "mechanism": "MCL1 is stabilized by CTSD; CTSD inhibition accelerates its degradation, promoting apoptosis.", "protein": "MCL1", "relationship_type": "causal", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Not glycosylated.", "mechanism": "TRIM21 promotes ubiquitination and degradation of BCL2, BCL-XL, and MCL1, enhancing apoptosis.", "protein": "TRIM21", "relationship_type": "protective", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Venetoclax-resistant AML", "glycan_involvement": "Glycosylation required for CTSD function.", "mechanism": "CTSD inhibition (by N-8) is effective in venetoclax-resistant AML models.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343803" }, { "confidence": "medium", "disease": "Venetoclax-resistant AML", "glycan_involvement": "Glycosylation may affect BCL2 drug sensitivity.", "mechanism": "BCL2 overexpression contributes to venetoclax resistance; CTSD inhibition destabilizes BCL2.", "protein": "BCL2", "relationship_type": "causal", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation is essential for CTSD lysosomal localization and function.", "mechanism": "CTSD suppresses TRIM21-mediated ubiquitination of anti-apoptotic proteins, promoting AML progression.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "causal", "source_pmcid": "PMC12343803" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Rubicon inhibits autophagosome-lysosome fusion, suppressing lipophagy and promoting hepatic lipid accumulation.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "causal", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Elevated Rubicon expression blocks autophagic flux, exacerbating steatosis and inflammation.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "causal", "source_pmcid": "PMC12343834" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Rubicon-mediated autophagy impairment contributes to progression from steatosis to fibrosis.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "causal", "source_pmcid": "PMC12343834" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Chronic autophagy inhibition by Rubicon may promote oncogenic transformation in liver.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "causal", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Silencing Rubicon restores autophagic flux, enhances lipophagy, and reduces hepatic lipid accumulation.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ASGPR recognizes terminal GalNAc residues on glycoproteins; glycan-mediated targeting is essential.", "mechanism": "ASGPR mediates hepatocyte-specific uptake of GalNAc-modified nanoparticles for siRNA delivery.", "protein": "ASGPR", "relationship_type": "therapeutic_target (for delivery)", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycan (GalNAc) modification is critical for ASGPR-mediated uptake.", "mechanism": "ASGPR enables hepatocyte-selective endocytosis of GalNAc-decorated siRNA nanoparticles in inflamed/fatty liver.", "protein": "ASGPR", "relationship_type": "therapeutic_target (for delivery)", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Rubicon expression correlates with disease severity and impaired autophagy in steatotic liver.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "Liver diseases (general)", "glycan_involvement": "Recognizes glycoproteins with terminal GalNAc; glycosylation is essential for ligand recognition.", "mechanism": "ASGPR expression is high on hepatocytes and can be used for liver-targeted therapies.", "protein": "ASGPR", "relationship_type": "biomarker", "source_pmcid": "PMC12343834" }, { "confidence": "medium", "disease": "Age-associated diseases", "glycan_involvement": "No direct glycosylation involvement for Rubicon described.", "mechanism": "Rubicon upregulation impairs autophagy, contributing to lipid accumulation in aging-related pathologies.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "causal", "source_pmcid": "PMC12343834" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "Mediates T cell rolling via glycan ligands (e.g., sialyl Lewis X).", "mechanism": "Loss of P-selectin expression on tumor endothelium reduces T cell infiltration, promoting immune evasion.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "Binds sialylated/fucosylated glycan ligands on T cells.", "mechanism": "Reduced E-selectin on tumor endothelium impairs T cell recruitment.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "N-glycosylation modulates ligand binding and stability.", "mechanism": "Downregulation in tumors reduces firm adhesion and transmigration of T cells.", "protein": "ICAM1", "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "N-glycosylation affects function and cell surface expression.", "mechanism": "Reduced VCAM1 impairs T cell adhesion and infiltration.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "O-glycosylation critical for ligand (integrin) binding.", "mechanism": "COUP-TFII-induced MAdCAM1 expression promotes T cell recruitment into tumors.", "protein": "MAdCAM1", "relationship_type": "protective", "source_pmcid": "PMC12343902" }, { "confidence": "high", "disease": "Tumor immune evasion", "glycan_involvement": "Defined by extended O-glycans with sialyl Lewis X; not induced by COUP-TFII alone.", "mechanism": "Lack of mature PNAd in tumor endothelium limits lymphocyte homing.", "protein": "PNAd", "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "Adds \u03b12-3 sialic acid to glycoproteins, enabling selectin binding.", "mechanism": "COUP-TFII upregulates St6gal1, promoting sialylation of selectin ligands for T cell recruitment.", "protein": "St6gal1", "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "low", "disease": "Tumor immune evasion", "glycan_involvement": "Heavily O-glycosylated; sialylation affects cell adhesion.", "mechanism": "Downregulated by COUP-TFII; loss of capillary marker associated with venular reprogramming.", "protein": "Podocalyxin (Podxl)", "protein_enriched": { "function": "DSP may be an important factor in dentinogenesis. DPP may bind high amount of calcium and facilitate initial mineralization of dentin matrix collagen as well as regulate the size and shape of the crys", "gene_name": "Dspp", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P97399" }, "relationship_type": "causal", "source_pmcid": "PMC12343902" }, { "confidence": "medium", "disease": "Tumor immune evasion", "glycan_involvement": "Glycosylation required for surface expression.", "mechanism": "Upregulated by COUP-TFII; marker of venular ECs associated with T cell recruitment.", "protein": "CD157", "protein_enriched": { "function": "Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly (PubMed:20002496, PubMed:21211722, PubMed:26841755). Also participates in several important DNA repair mech", "gene_name": "NAP1L1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P55209" }, "relationship_type": "protective", "source_pmcid": "PMC12343902" }, { "confidence": "low", "disease": "Tumor immune evasion", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "COUP-TFII upregulates Ephb4, supporting venous identity and T cell recruitment.", "protein": "Ephrin B4 (Ephb4)", "protein_enriched": { "function": "Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The si", "gene_name": "EPHB4", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06356OH", "G25451PN", "G62765YT", "G84452RH", "G08290VR", "G10486CT", "G39446WN", "G59626AS", "G72787SB", "G83460ZZ" ], "uniprot_id": "P54760" }, "relationship_type": "protective", "source_pmcid": "PMC12343902" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation; not a glycoprotein.", "mechanism": "Accumulation of aSyn in Lewy bodies is a hallmark; SNCA gene triplication causes familial PD.", "protein": "Alpha-synuclein (aSyn)", "relationship_type": "causal", "source_pmcid": "PMC12343942" }, { "confidence": "high", "disease": "Dementia with Lewy bodies", "glycan_involvement": "No direct glycosylation; not a glycoprotein.", "mechanism": "aSyn aggregates form Lewy bodies/neurotoxicity.", "protein": "Alpha-synuclein (aSyn)", "relationship_type": "causal", "source_pmcid": "PMC12343942" }, { "confidence": "high", "disease": "Familial Parkinsonism", "glycan_involvement": "No direct glycosylation; not a glycoprotein.", "mechanism": "Gene duplication/triplication increases aSyn expression, leading to disease.", "protein": "Alpha-synuclein (aSyn)", "relationship_type": "causal", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation not discussed in this context.", "mechanism": "Presynaptic marker; levels unaltered by aSyn overexpression in this study.", "protein": "SNAP-25", "relationship_type": "biomarker", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation not discussed in this context.", "mechanism": "Postsynaptic marker; area increased but intensity unchanged with aSyn overexpression.", "protein": "PSD-95", "relationship_type": "biomarker", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation not discussed in this context.", "mechanism": "Presynaptic marker; number of syntaxin-positive puncta increased with aSyn overexpression.", "protein": "Syntaxin", "relationship_type": "biomarker", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation not discussed in this context.", "mechanism": "aSyn interacts with VAMP2 to regulate synaptic vesicle function.", "protein": "VAMP2", "relationship_type": "mechanistic", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation not discussed in this context.", "mechanism": "aSyn interacts with synapsin to regulate synaptic vesicle function.", "protein": "Synapsin", "protein_enriched": { "function": "Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pr", "gene_name": "SYN1", "glycan_count": 1, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17600" }, "relationship_type": "mechanistic", "source_pmcid": "PMC12343942" }, { "confidence": "high", "disease": "Lewy body diseases", "glycan_involvement": "No direct glycosylation; not a glycoprotein.", "mechanism": "Intraneuronal accumulation of aSyn is a neuropathological hallmark.", "protein": "Alpha-synuclein (aSyn)", "relationship_type": "causal", "source_pmcid": "PMC12343942" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "No direct glycosylation; not a glycoprotein.", "mechanism": "Glutamatergic neurons are resilient to aSyn overexpression at moderate levels.", "protein": "Alpha-synuclein (aSyn)", "relationship_type": "protective", "source_pmcid": "PMC12343942" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "DprE1 catalyzes a key step in the synthesis of decaprenylphosphoryl-D-arabinose, a glycan precursor for arabinogalactan.", "mechanism": "DprE1 is essential for arabinogalactan biosynthesis in the mycobacterial cell wall; inhibition leads to cell wall disruption and bacterial death.", "protein": "Decaprenylphosphoryl-\u03b2-D-ribose 2\u2032-epimerase (DprE1)", "protein_enriched": { "function": "May catalyze the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides and confer resistance to aminoglycosides (By similarity). In vitro assays sho", "gene_name": "aac", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P9WQG9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343961" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "No direct glycosylation involvement; enzyme is not a glycoprotein but is targeted in anti-TB therapy.", "mechanism": "Mtb-DHFR is essential for folate biosynthesis; inhibition impairs nucleotide synthesis and bacterial growth.", "protein": "Dihydrofolate reductase (Mtb-DHFR)", "protein_enriched": { "function": "Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis", "gene_name": "folA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P9WNX1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343961" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for antiphospholipid syndrome, which is a risk factor for RPL.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12343984" }, { "confidence": "high", "disease": "threatened miscarriage", "glycan_involvement": "Glycosylation is essential for hCG stability and bioactivity.", "mechanism": "hCG levels are used to confirm pregnancy and monitor viability in threatened miscarriage.", "protein": "human chorionic gonadotropin", "relationship_type": "biomarker", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "placental insufficiency", "glycan_involvement": "Glycosylation modulates VEGF secretion and receptor binding.", "mechanism": "Reduced VEGF expression in endometrium is associated with luteal phase defect and placental insufficiency, contributing to miscarriage.", "protein": "vascular endothelial growth factor", "relationship_type": "causal", "source_pmcid": "PMC12343984" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Targets glycoprotein antigens; glycosylation may affect epitope recognition.", "mechanism": "Presence of anticardiolipin antibodies is diagnostic for antiphospholipid syndrome, a cause of RPL.", "protein": "anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12343984" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Targets glycoprotein antigens; glycosylation may affect epitope recognition.", "mechanism": "Lupus anticoagulant is a diagnostic marker for antiphospholipid syndrome, increasing risk of RPL.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "recurrent pregnancy loss (RPL)", "glycan_involvement": "HLA glycosylation affects immune recognition and tolerance.", "mechanism": "HLA typing is used in immunological investigations of RPL.", "protein": "human leukocyte antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "luteal phase defect", "glycan_involvement": "Glycosylation may affect receptor localization and function.", "mechanism": "Progesterone receptor signaling is targeted by progestogen therapy to correct luteal phase defect and prevent miscarriage.", "protein": "progesterone receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "threatened miscarriage", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Progesterone promotes Th2 cytokines (IL-6) to support maternal immune tolerance and reduce miscarriage risk.", "protein": "interleukin-6", "relationship_type": "protective", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "threatened miscarriage", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Progesterone increases IL-10, promoting anti-inflammatory environment and reducing miscarriage risk.", "protein": "interleukin-10", "relationship_type": "protective", "source_pmcid": "PMC12343984" }, { "confidence": "medium", "disease": "recurrent pregnancy loss (RPL)", "glycan_involvement": "Glycosylation affects TNF-alpha secretion and receptor binding.", "mechanism": "Elevated TNF-alpha (Th1 cytokine) is associated with increased risk of miscarriage; progesterone suppresses TNF-alpha.", "protein": "tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12343984" }, { "confidence": "high", "disease": "Obese NAFLD", "glycan_involvement": "PK-1 is a secreted glycoprotein; glycosylation may affect secretion/stability.", "mechanism": "PK-1 expression is reduced in Obese NAFLD; higher PK-1 correlates with T-reg and CD8+ cells, suggesting a protective immune surveillance role.", "protein": "Prokineticin-1 (PK-1)", "protein_enriched": { "function": "May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts", "gene_name": "PROK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC23" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344004" }, { "confidence": "high", "disease": "Obese NAFLD", "glycan_involvement": "PK-2 is a secreted glycoprotein; glycosylation may influence receptor binding.", "mechanism": "PK-2 is upregulated in Obese NAFLD, promotes inflammation and fibrosis, and negatively correlates with C-type lectin.", "protein": "Prokineticin-2 (PK-2)", "protein_enriched": { "function": "Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ ", "gene_name": "TMBIM4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC24" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344004" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Glycosylation may modulate PK-2's pro-fibrotic activity.", "mechanism": "PK-2 drives fibrosis via inflammatory cytokine production and hepatic stellate cell activation.", "protein": "Prokineticin-2 (PK-2)", "protein_enriched": { "function": "Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ ", "gene_name": "TMBIM4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC24" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12344004" }, { "confidence": "medium", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect function.", "mechanism": "PK-1 is upregulated in MetS, suggesting a protective/immune regulatory role that is lost in progression to Obese NAFLD.", "protein": "Prokineticin-1 (PK-1)", "protein_enriched": { "function": "May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts", "gene_name": "PROK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC23" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344004" }, { "confidence": "medium", "disease": "Obese NAFLD", "glycan_involvement": "Potential glycosylation may affect intracellular trafficking.", "mechanism": "FABP-5 is upregulated in Obese NAFLD, correlates with PK-2 and IL-10, linking lipid metabolism and inflammation.", "protein": "Fatty Acid Binding Protein 5 (FABP-5)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344004" }, { "confidence": "high", "disease": "Obese NAFLD", "glycan_involvement": "IL-10 is glycosylated; glycosylation is important for secretion and stability.", "mechanism": "IL-10 is elevated and strongly correlates with T-reg, CD4+, and CD8+ cells, indicating anti-inflammatory response.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344004" }, { "confidence": "medium", "disease": "Obese NAFLD", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Nrf-2 expression is reduced in Obese NAFLD, leading to increased oxidative stress and disease progression.", "protein": "Nrf-2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O54968" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344004" }, { "confidence": "medium", "disease": "Obese NAFLD", "glycan_involvement": "C-type lectins bind glycans; altered glycosylation may affect immune signaling.", "mechanism": "PK-2 negatively correlates with C-type lectin, implicating altered glycan recognition in inflammation.", "protein": "C-type lectin", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344004" }, { "confidence": "high", "disease": "NASH", "glycan_involvement": "Glycosylation may modulate PK-2's inflammatory activity.", "mechanism": "PK-2 upregulation promotes chronic inflammation and fibrosis, driving NASH progression.", "protein": "Prokineticin-2 (PK-2)", "protein_enriched": { "function": "Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ ", "gene_name": "TMBIM4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC24" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12344004" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect PK-1's role in angiogenesis.", "mechanism": "PK-1 is implicated in tumor progression, angiogenesis, and metastasis in HCC.", "protein": "Prokineticin-1 (PK-1)", "protein_enriched": { "function": "May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts", "gene_name": "PROK2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HC23" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12344004" }, { "confidence": "high", "disease": "Cancer (Breast, Pancreatic, Mesothelioma, Colon, Lung, Ovarian, Glioblastoma)", "glycan_involvement": "GFPT2 drives hexosamine biosynthesis, increasing UDP-GlcNAc for glycosylation of oncogenic proteins.", "mechanism": "Upregulation and phosphorylation of GFPT2 promotes cancer cell proliferation, invasion, EMT, and poor survival.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344200" }, { "confidence": "medium", "disease": "Diabetes Mellitus (Type 2)", "glycan_involvement": "Reduced UDP-GlcNAc affects glycosylation of insulin signaling proteins.", "mechanism": "Ethnicity-associated dysregulation of GFPT2 mRNA impairs glucose flux and hexosamine pathway.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344200" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Defective glycosylation compromises protein folding in neurons.", "mechanism": "Reduced GFPT2 expression impairs hexosamine pathway, leading to protein misfolding and neuronal dysfunction.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12344200" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "O-GlcNAcylation of YBX1 regulates immune microenvironment and tumor progression.", "mechanism": "GFPT2-mediated O-GlcNAcylation of YBX1 promotes nuclear localization and transcription of IL-18, driving malignancy.", "protein": "YBX1", "relationship_type": "causal", "source_pmcid": "PMC12344200" }, { "confidence": "high", "disease": "Mesothelioma", "glycan_involvement": "O-GlcNAcylation enhances transcriptional activity of NF-\u03baB.", "mechanism": "GFPT2-mediated O-GlcNAcylation at Ser75 of p65 activates NF-\u03baB signaling, promoting cancer growth.", "protein": "p65 (RELA)", "relationship_type": "causal", "source_pmcid": "PMC12344200" }, { "confidence": "medium", "disease": "Cancer (Metastasis)", "glycan_involvement": "Glycosylation modulates integrin-mediated cell adhesion.", "mechanism": "Altered glycosylation of integrins affects ECM adhesion, facilitating metastasis.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC12344200" }, { "confidence": "medium", "disease": "Noonan Syndrome-like Disorder", "glycan_involvement": "Hexosamine pathway influences glycosylation in neurodevelopment.", "mechanism": "GFPT2 co-regulated proteins enriched in neuronal synapses are associated with NSLL.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344200" }, { "confidence": "medium", "disease": "Mental Retardation", "glycan_involvement": "Glycosylation affects synaptic protein function.", "mechanism": "GFPT2 co-regulated proteins in synaptic regions linked to cognitive impairment.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344200" }, { "confidence": "medium", "disease": "Cervical Artery Dissection", "glycan_involvement": "Glycosylation maintains ECM integrity.", "mechanism": "Loss of glycosylation in ECM proteins due to GFPT2 deficiency leads to vascular structural weakness.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "causal", "source_pmcid": "PMC12344200" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Enhanced hexosamine pathway supports glycosylation of oncogenic proteins.", "mechanism": "GFPT2 is highly overexpressed in GBM tumors and cell lines.", "protein": "GFPT2", "protein_enriched": { "function": "Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins", "gene_name": "GFPT2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O94808" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344200" }, { "confidence": "high", "disease": "Cadmium-induced kidney injury", "glycan_involvement": "GPX4 is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "Suppression of renal GPX4 by exosomal miR-2137 from Cd-treated hepatocytes triggers ferroptosis and kidney injury.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "high", "disease": "Cadmium-induced liver injury", "glycan_involvement": "GPX4 is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "Cd exposure downregulates hepatic GPX4, promoting ferroptosis and liver injury.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "high", "disease": "Ferroptosis", "glycan_involvement": "Not specified.", "mechanism": "GPX4 loss leads to accumulation of lipid peroxides and ferroptotic cell death.", "protein": "GPX4", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "high", "disease": "Cadmium-induced kidney injury", "glycan_involvement": "Not specified.", "mechanism": "Restoration of GPX4 (e.g., by selenium or miR-2137 inhibition) protects against Cd-induced renal ferroptosis.", "protein": "GPX4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344268" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "FTH1 is a glycoprotein; glycosylation not discussed.", "mechanism": "Downregulation of FTH1 impairs iron storage, promoting iron overload and ferroptosis.", "protein": "FTH1", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role ", "gene_name": "Ftl1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29391" }, "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "SLC3A2 is a glycoprotein; glycosylation not discussed.", "mechanism": "Downregulation reduces cystine uptake, depleting GSH and sensitizing to ferroptosis.", "protein": "SLC3A2", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "SLC7A11 is a glycoprotein; glycosylation not discussed.", "mechanism": "Upregulation increases cystine import, supporting GSH synthesis and ferroptosis resistance.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12344268" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "SLC40A1 is a glycoprotein; glycosylation not discussed.", "mechanism": "Downregulation impairs iron export, increasing intracellular iron and promoting ferroptosis.", "protein": "SLC40A1", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "medium", "disease": "Ferroptosis", "glycan_involvement": "GCLC is a glycoprotein; glycosylation not discussed.", "mechanism": "Downregulation impairs GSH synthesis, reducing antioxidant defense and promoting ferroptosis.", "protein": "GCLC", "relationship_type": "causal", "source_pmcid": "PMC12344268" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Not specified.", "mechanism": "GPX4 detoxifies lipid peroxides, reducing oxidative stress.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12344268" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Hyaluronan binding and variant-specific glycosylation modulate function.", "mechanism": "CD44-HA interaction promotes CSC adhesion, immune evasion, and therapy resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation essential for epitope recognition and function.", "mechanism": "CD133 marks CSCs, mediates stemness and resistance via glycosylation-dependent signaling.", "protein": "CD133 (Prominin-1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation affects cell-cell adhesion and immune recognition.", "mechanism": "EpCAM regulates CSC adhesion, proliferation, and EMT; targeted by CAR-T therapies.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Sialylation and O-glycosylation modulate anti-adhesive properties.", "mechanism": "PODXL overexpression correlates with CSC phenotype and poor prognosis.", "protein": "Podocalyxin (PODXL)", "relationship_type": "biomarker", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Heparan sulfate chains mediate growth factor binding.", "mechanism": "Syndecan-1 enhances EMT and growth factor signaling in CSCs.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "Heparan sulfate modification required for signaling.", "mechanism": "Glypican-3 promotes CSC stemness and EMT via Wnt signaling.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "O-glycosylation and sialylation mask immune epitopes.", "mechanism": "Mucins interact with immune checkpoints, dampening cytotoxic responses.", "protein": "Mucin family (e.g., MUC1)", "relationship_type": "biomarker/immune evasion", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates ECM binding and signaling.", "mechanism": "CD49f mediates CSC niche interactions and metastasis.", "protein": "Integrin \u03b16 (CD49f)", "relationship_type": "biomarker", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation affects receptor activation and ligand binding.", "mechanism": "EGFR regulates CSC stemness, metabolism, and therapy resistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation influences transporter stability and localization.", "mechanism": "ABCG2 mediates drug resistance and CSC survival.", "protein": "ABCG2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344368" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "FLOT1 localizes to Golgi and lipid rafts, influencing glycoprotein trafficking and modification.", "mechanism": "Promotes HCC progression by activating TFE3-mediated Golgi stress response via inhibition and ubiquitination of mTORC1/2, leading to increased proliferation, migration, and invasion.", "protein": "Flotillin-1 (FLOT1)", "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation status may affect FLOT1 localization and function.", "mechanism": "High FLOT1 expression correlates with poor prognosis and reduced overall survival in HCC patients.", "protein": "Flotillin-1 (FLOT1)", "relationship_type": "biomarker", "source_pmcid": "PMC12344369" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GP73 is a glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "Induces cytokine/chemokine release, modulating tumor-associated macrophage phenotype and promoting HCC growth/metastasis.", "protein": "Golgi protein 73 (GP73/GOLPH2)", "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GOLPH3 is involved in glycosylation processes in the Golgi.", "mechanism": "Upregulation inhibits apoptosis, promotes proliferation and invasion of HCC cells.", "protein": "Golgi phosphoprotein 3 (GOLPH3)", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1 (PubMed:10567565, PubMed:20818336, PubMed:28760339, PubMed:29042532, PubMed:38512451). Binds specifically and direc", "gene_name": "KPNA4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00629" }, "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GM130 recruits RNA-binding proteins to Golgi, impacting glycoprotein synthesis.", "mechanism": "Upregulated by FLOT1, supports Golgi stress response and tumor cell survival.", "protein": "GM130", "protein_enriched": { "function": "RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:1608602", "gene_name": "UPF1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q92900" }, "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Giantin is a glycoprotein involved in Golgi vesicle tethering.", "mechanism": "Upregulated by FLOT1, contributes to Golgi structure and tumor cell migration/invasion.", "protein": "Giantin", "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "p115 is a glycoprotein involved in ER-Golgi transport.", "mechanism": "Upregulated by FLOT1, mediates vesicular transport and supports Golgi stress response.", "protein": "p115", "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "TFE3 regulates transcription of glycosyltransferases and Golgi-associated genes.", "mechanism": "Nuclear translocation (activated by FLOT1 via mTORC1/2 inhibition) drives Golgi stress gene expression, promoting HCC cell survival.", "protein": "Transcription factor E3 (TFE3)", "relationship_type": "causal", "source_pmcid": "PMC12344369" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Indirect; mTORC1/2 regulates phosphorylation of TFE3, affecting glycosylation gene expression.", "mechanism": "Inhibition by FLOT1 promotes TFE3 nuclear translocation and Golgi stress, supporting tumor progression.", "protein": "Mechanistic target of rapamycin complex 1/2 (mTORC1/2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344369" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "No direct glycosylation involvement.", "mechanism": "Activation (upon FLOT1 knockdown) promotes apoptosis of HCC cells.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "protective", "source_pmcid": "PMC12344369" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "Transferrin is a glycoprotein; glycosylation affects its stability and iron-binding capacity.", "mechanism": "Elevated transferrin and iron overload are associated with increased seizure susceptibility and oxidative stress.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344419" }, { "confidence": "high", "disease": "Epilepsy", "glycan_involvement": "TfR1 is a glycoprotein; glycosylation modulates receptor trafficking and iron transport.", "mechanism": "TfR1 mediates neuronal iron uptake; upregulation leads to iron overload and ferroptosis in epilepsy.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12344419" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "P-gp is N-glycosylated; glycosylation influences membrane localization and drug efflux function.", "mechanism": "Seizures upregulate P-gp, affecting drug resistance and possibly iron/ROS handling.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344419" }, { "confidence": "medium", "disease": "Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS)", "glycan_involvement": "Klotho is a glycoprotein; glycosylation is essential for secretion and neuroprotective function.", "mechanism": "Klotho overexpression inhibits ferroptosis, reduces iron overload, and improves cognitive deficits.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12344419" }, { "confidence": "medium", "disease": "Post-traumatic epilepsy (PTE)", "glycan_involvement": "Glycosylation of transferrin may affect its half-life and iron delivery to neurons.", "mechanism": "Elevated transferrin after brain injury correlates with iron overload and seizure development.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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"G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344419" }, { "confidence": "medium", "disease": "Mesial temporal lobe epilepsy (MTLE)", "glycan_involvement": "TfR1 glycosylation may regulate its expression and iron uptake in neurons.", "mechanism": "Redistribution of iron via TfR1 is linked to seizure progression and iron accumulation in MTLE.", "protein": "Transferrin receptor 1 (TfR1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344419" }, { "confidence": "low", "disease": "Ischemic optic neuropathy (ION)", "glycan_involvement": "N-glycosylation modulates P-gp function in the blood-brain barrier.", "mechanism": "Seizure-induced upregulation of P-gp may contribute to ION via altered iron and drug transport.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12344419" }, { "confidence": "medium", "disease": "Epilepsy-associated cognitive disorder (ECD)", "glycan_involvement": "Glycosylation required for Klotho's neuroprotective activity.", "mechanism": "Klotho inhibits ferroptosis and protects against cognitive decline in epilepsy models.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards 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It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "protective", "source_pmcid": "PMC12344419" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "ApoB is N-glycosylated, affecting its secretion and lipid transport.", "mechanism": "Elevated ApoB levels are associated with increased risk and severity of MAFLD in lean BD patients.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "ApoA1 glycosylation modulates HDL function and anti-inflammatory properties.", "mechanism": "Lower ApoA1 levels are observed in MAFLD, suggesting reduced HDL formation and impaired cholesterol efflux.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344461" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "HDL contains glycoproteins (ApoA1, ApoA2) whose glycosylation affects HDL stability and function.", "mechanism": "Higher HDL levels protect against MAFLD by promoting cholesterol efflux and anti-inflammatory effects.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity and stability.", "mechanism": "Elevated GGT is a risk factor for MAFLD, reflecting hepatic oxidative stress and metabolic dysfunction.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "ER\u03b1 glycosylation may influence receptor localization and signaling.", "mechanism": "ER\u03b1 activation reduces hepatic inflammation and steatosis, mitigating MAFLD progression, especially in females.", "protein": "Estrogen Receptor alpha (ER\u03b1)", "protein_enriched": { "function": "Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.", "gene_name": "ESR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P03372" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "MDM2 may regulate glycoprotein turnover via ubiquitination.", "mechanism": "MDM2 inhibits TG-VLDL secretion, promoting hepatic triglyceride accumulation and MAFLD.", "protein": "MDM2", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apo", "gene_name": "MDM2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q00987" }, "relationship_type": "causal", "source_pmcid": "PMC12344461" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation of ApoB affects LDL particle formation and atherogenicity.", "mechanism": "Elevated ApoB increases cardiovascular risk in MAFLD and BD patients.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12344461" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of HDL-associated proteins modulates anti-atherogenic functions.", "mechanism": "HDL reduces cardiovascular risk via reverse cholesterol transport and anti-inflammatory effects.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation affects ApoB secretion and lipid metabolism.", "mechanism": "ApoB elevation is linked to metabolic syndrome features in BD and MAFLD.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12344461" }, { "confidence": "medium", "disease": "Bipolar Disorder", "glycan_involvement": "ApoA1 glycosylation influences anti-inflammatory and neuroprotective effects.", "mechanism": "Lower ApoA1/HDL levels are common in BD, contributing to metabolic risk.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12344461" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "ATF6 activation is part of the UPR, which is regulated by glycosylation status of ER proteins.", "mechanism": "ATF6 suppresses endothelial inflammation via negative transcriptional control of TRIM10/NF-\u03baB signaling.", "protein": "ATF6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Small-for-size syndrome (SFSS)", "glycan_involvement": "UPR activation involves glycoprotein folding and glycan-dependent ER stress signaling.", "mechanism": "ATF6 activation in LSECs protects against inflammation and injury post extended hepatectomy.", "protein": "ATF6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Endothelial inflammation", "glycan_involvement": "Glycosylation affects ATF6 activation and ER stress response.", "mechanism": "ATF6 negatively regulates TRIM10, reducing NF-\u03baB activation and inflammatory cytokine production.", "protein": "ATF6", "relationship_type": "protective", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Endothelial inflammation", "glycan_involvement": "TRIM10 function may be modulated by glycosylation, impacting its E3 ligase activity.", "mechanism": "TRIM10 activates NF-\u03baB signaling via TBK1 ubiquitination, promoting inflammation.", "protein": "TRIM10", "relationship_type": "causal", "source_pmcid": "PMC12344622" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "GRP78 is an N-glycosylated chaperone essential for protein folding.", "mechanism": "GRP78 upregulation indicates ER stress and UPR activation post hepatectomy.", "protein": "GRP78", "relationship_type": "biomarker", "source_pmcid": "PMC12344622" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "GRP94 glycosylation is required for its chaperone function.", "mechanism": "GRP94 upregulation reflects ER stress and UPR activation in liver injury.", "protein": "GRP94", "relationship_type": "biomarker", "source_pmcid": "PMC12344622" }, { "confidence": "medium", "disease": "Endothelial inflammation", "glycan_involvement": "Glycosylation may regulate NF-\u03baB nuclear translocation and activity.", "mechanism": "NF-\u03baB p65 activation drives proinflammatory cytokine expression in LSECs.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "causal", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Liver regeneration impairment", "glycan_involvement": "ATF6 activation depends on ER glycoprotein homeostasis.", "mechanism": "ATF6 deficiency impairs regeneration by increasing inflammation and apoptosis.", "protein": "ATF6", "relationship_type": "protective", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Liver apoptosis", "glycan_involvement": "Glycosylation status influences ATF6 activation and anti-apoptotic signaling.", "mechanism": "ATF6 suppresses apoptosis by reducing inflammatory signaling post hepatectomy.", "protein": "ATF6", "relationship_type": "protective", "source_pmcid": "PMC12344622" }, { "confidence": "medium", "disease": "Liver ischemia\u2013reperfusion injury", "glycan_involvement": "ER glycoprotein folding and glycan-dependent stress responses are involved.", "mechanism": "ATF6 activation induces protective factors and reduces endothelial inflammation.", "protein": "ATF6", "relationship_type": "protective", "source_pmcid": "PMC12344622" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "TYR is a glycoprotein; glycosylation is essential for its stability and enzymatic function.", "mechanism": "TYR activity is suppressed in vitiligo; MMF restores TYR expression and activity, promoting melanogenesis.", "protein": "Tyrosinase (TYR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344676" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "TYRP-1 is a glycoprotein; glycosylation affects its function and localization.", "mechanism": "TYRP-1 expression is reduced in depigmentation; MMF upregulates TYRP-1, aiding melanin synthesis.", "protein": "Tyrosinase-related protein 1 (TYRP-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "SILV is a glycoprotein; glycosylation is required for fibril formation in melanosomes.", "mechanism": "SILV/PMEL expression correlates with melanocyte differentiation and pigmentation; upregulated by MMF.", "protein": "Premelanosome protein (SILV/PMEL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "\u03b2-catenin is N-glycosylated, which may affect its stability and signaling.", "mechanism": "Activation of \u03b2-catenin via WNT signaling promotes melanocyte regeneration; MMF stabilizes \u03b2-catenin.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "GSK3\u03b2 phosphorylates \u03b2-catenin, leading to its degradation; MMF inhibits GSK3\u03b2, enhancing WNT signaling.", "protein": "Glycogen synthase kinase 3 beta (GSK3\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "DKK is a secreted glycoprotein; glycosylation affects secretion and activity.", "mechanism": "DKK modulates WNT signaling; MMF upregulates DKK, influencing melanocyte biology.", "protein": "Dickkopf-related protein (DKK)", "relationship_type": "regulatory", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "IFN-\u03b3 is glycosylated, which influences its stability and receptor binding.", "mechanism": "IFN-\u03b3 is upregulated in vitiligo, promoting depigmentation; MMF reduces IFN-\u03b3 levels.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "causal", "source_pmcid": "PMC12344676" }, { "confidence": "high", "disease": "Hydroquinone-induced depigmentation", "glycan_involvement": "Glycosylation is required for TYR function; inhibition affects glycoprotein activity.", "mechanism": "Hydroquinone inhibits TYR, leading to melanin loss.", "protein": "Tyrosinase (TYR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12344676" }, { "confidence": "high", "disease": "Hydroquinone-induced depigmentation", "glycan_involvement": "Glycosylation is essential for TYRP-1 function.", "mechanism": "Hydroquinone suppresses TYRP-1, contributing to pigment loss.", "protein": "Tyrosinase-related protein 1 (TYRP-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12344676" }, { "confidence": "medium", "disease": "Hydroquinone-induced depigmentation", "glycan_involvement": "Glycosylation required for SILV/PMEL function.", "mechanism": "SILV/PMEL downregulation marks melanocyte dysfunction in depigmentation.", "protein": "Premelanosome protein (SILV/PMEL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12344676" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Fibulin2 is a glycoprotein; glycosylation may affect its secretion and stability in plasma.", "mechanism": "Fibulin2 levels are significantly elevated in plasma of sepsis patients compared to controls; reflects host response to infection and organ dysfunction.", "protein": "Fibulin2", "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Glycosylation may modulate Fibulin2's extracellular matrix interactions during severe inflammation.", "mechanism": "Fibulin2 levels are higher in septic shock than in sepsis without shock; correlates with severity.", "protein": "Fibulin2", "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "high", "disease": "28-day mortality in sepsis", "glycan_involvement": "Glycosylation may influence Fibulin2's half-life and detectability in plasma.", "mechanism": "Elevated Fibulin2 predicts increased risk of death within 28 days in sepsis patients.", "protein": "Fibulin2", "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "CRP is glycosylated; glycan structure affects its function and clearance.", "mechanism": "CRP is elevated in sepsis but less sensitive/specific than Fibulin2.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "PCT glycosylation may affect its processing and secretion.", "mechanism": "PCT is elevated in sepsis but inferior to Fibulin2 for diagnosis.", "protein": "PCT", "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "medium", "disease": "Infection (general)", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Fibulin2 is upregulated in plasma during infection, indicating early host response.", "protein": "Fibulin2", "relationship_type": "biomarker", "source_pmcid": "PMC12344871" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Albumin is N-glycosylated, which affects its stability and serum half-life; hypoalbuminemia alters AG calculation.", "mechanism": "Serum albumin levels are used to correct the anion gap (ACAG), which is associated with mortality risk in HF.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344888" }, { "confidence": "high", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation status may affect albumin's clearance and function in AKI.", "mechanism": "Low albumin is common in AKI and impacts ACAG, which predicts mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344888" }, { "confidence": "high", "disease": "Critical illness (ICU mortality)", "glycan_involvement": "Glycosylation may influence albumin's negative charge and thus its contribution to AG.", "mechanism": "Albumin-corrected anion gap (ACAG) is a better predictor of ICU mortality than AG or albumin alone.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344888" }, { "confidence": "high", "disease": "Heart failure with acute kidney injury", "glycan_involvement": "Altered glycosylation may affect albumin's serum levels and function.", "mechanism": "Elevated ACAG (which uses albumin) is linearly associated with increased short- and long-term mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344888" }, { "confidence": "medium", "disease": "Metabolic acidosis in HF/AKI", "glycan_involvement": "Glycosylation may modulate albumin's charge and buffering capacity.", "mechanism": "Albumin is a major unmeasured anion; hypoalbuminemia leads to underestimation of metabolic derangements unless corrected.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12344888" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "Transferrin is N-glycosylated, which affects its stability and receptor binding.", "mechanism": "Transferrin saturation (TSAT) is used to assess iron availability; low TSAT indicates iron deficiency.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Iron deficiency", "glycan_involvement": "Ferritin is glycosylated, influencing its serum half-life and immunoreactivity.", "mechanism": "Serum ferritin reflects iron stores; low ferritin is diagnostic for iron deficiency.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Erythropoietin is heavily glycosylated (N- and O-glycans), essential for bioactivity and serum half-life.", "mechanism": "Erythropoietin-stimulating agents are used to treat anemia by promoting erythropoiesis.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation modulates transferrin's interaction with its receptor and iron transport.", "mechanism": "TSAT and transferrin levels are used to assess iron status in heart failure patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects ferritin's immunodetection and stability.", "mechanism": "Ferritin is measured to evaluate iron stores in heart failure patients with anemia.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "CRP is glycosylated, affecting its solubility and immune function.", "mechanism": "CRP is measured to assess systemic inflammation, which can contribute to anemia of chronic disease.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "medium", "disease": "Iron deficiency", "glycan_involvement": "N-glycosylation is critical for receptor function and cell-surface expression.", "mechanism": "Transferrin receptor levels increase in iron deficiency, reflecting cellular iron demand.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation is required for erythropoietin's stability and activity.", "mechanism": "ESA therapy is used in CKD-related anemia due to reduced endogenous erythropoietin.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345016" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycosylation patterns may occur in malignancy, affecting transferrin isoforms.", "mechanism": "Iron deficiency anemia may prompt cancer screening; transferrin levels are part of the diagnostic work-up.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may influence ferritin's immunoreactivity in cancer states.", "mechanism": "Low ferritin in anemia may trigger investigation for occult cancer.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345016" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycation of hemoglobin (non-enzymatic addition of glucose to N-terminal valine of beta chain).", "mechanism": "HbA1c reflects average blood glucose levels and is used to monitor glycemic control in T2DM.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "high", "disease": "Cardiovascular Autonomic Neuropathy (CAN)", "glycan_involvement": "Glycation alters hemoglobin structure, reflecting chronic hyperglycemia.", "mechanism": "Elevated HbA1c is associated with increased risk and severity of CAN in T2DM patients.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "LDL particles contain glycosylated apolipoprotein B; glycosylation affects LDL metabolism.", "mechanism": "LDL levels are monitored as part of cardiovascular risk assessment in T2DM.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Cardiovascular Autonomic Neuropathy (CAN)", "glycan_involvement": "Glycosylation status may influence LDL particle function and clearance.", "mechanism": "Elevated LDL is a risk factor for CAN and other cardiovascular complications in diabetes.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Lipoproteins are glycosylated, affecting their metabolism and atherogenicity.", "mechanism": "High triglyceride levels are common in T2DM and contribute to cardiovascular risk.", "protein": "Triglyceride-rich Lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Cardiovascular Autonomic Neuropathy (CAN)", "glycan_involvement": "Vitamin B12 is transported in blood bound to glycoproteins (transcobalamin); glycosylation affects stability and uptake.", "mechanism": "Mecobalamin is used as a neurotrophic agent to support nerve function in CAN.", "protein": "Mecobalamin (Vitamin B12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia, a driver of nephropathy.", "mechanism": "Elevated HbA1c is associated with increased risk of diabetic nephropathy.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "high", "disease": "Coronary Heart Disease", "glycan_involvement": "Glycosylation of apolipoprotein B modulates LDL function and atherogenicity.", "mechanism": "High LDL is a causal factor in atherosclerosis and coronary heart disease.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12345026" }, { "confidence": "medium", "disease": "Sudden Cardiac Death", "glycan_involvement": "Glycation reflects poor glycemic control, increasing cardiovascular risk.", "mechanism": "High HbA1c is associated with increased risk of sudden cardiac death in diabetes.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345026" }, { "confidence": "high", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation affects LDL particle stability and interaction with arterial walls.", "mechanism": "Elevated LDL promotes plaque formation and myocardial infarction.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "causal", "source_pmcid": "PMC12345026" }, { "confidence": "high", "disease": "Cerebral small vessel disease (cSVD)", "glycan_involvement": "VCAM1 is a heavily N-glycosylated adhesion molecule; glycosylation modulates leukocyte binding.", "mechanism": "Upregulation in endothelial cells promotes leukocyte adhesion, capillary stalling, and vascular inflammation.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "Cerebral small vessel disease (cSVD)", "glycan_involvement": "CD31 is N-glycosylated, which affects cell-cell adhesion.", "mechanism": "Used as an endothelial marker to assess vascular integrity; altered expression reflects endothelial dysfunction.", "protein": "CD31 (PECAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12345092" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Occludin is N-glycosylated; glycosylation is important for tight junction assembly.", "mechanism": "Reduced occludin in endothelial cells leads to impaired tight junctions and BBB leakage.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Claudin-5 is N-glycosylated; glycosylation affects barrier properties.", "mechanism": "Claudin-5 is a tight junction protein; its expression reflects BBB integrity.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "COL4A1/2-related cSVD", "glycan_involvement": "Collagen IV is glycosylated; glycosylation affects basement membrane stability.", "mechanism": "Suppressed COL4A1 signaling in endothelial cells is linked to inherited forms of cSVD.", "protein": "COL4A1", "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "NOTCH3-related cSVD (e.g., CADASIL)", "glycan_involvement": "NOTCH3 is O-fucosylated and O-glucosylated; glycosylation modulates receptor function.", "mechanism": "Reduced NOTCH3 signaling in endothelial cells is associated with cSVD pathogenesis.", "protein": "NOTCH3", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular do", "gene_name": "NOTCH3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G02815KT", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G20579QQ", "G73968GN", "G83646BJ", "G71142DF" ], "uniprot_id": "Q9UM47" }, "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "high", "disease": "Leukocyte adhesion/vascular inflammation", "glycan_involvement": "N-glycans on VCAM1 regulate leukocyte binding affinity.", "mechanism": "VCAM1 upregulation increases leukocyte-endothelial interactions, promoting inflammation.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "Cerebral small vessel disease (cSVD)", "glycan_involvement": "CD13 is N-glycosylated, influencing enzymatic activity and cell interactions.", "mechanism": "CD13 is a pericyte marker; altered expression reflects pericyte dysfunction in cSVD.", "protein": "CD13 (ANPEP)", "protein_enriched": { "function": "Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of var", "gene_name": "ANPEP", "glycan_count": 197, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G07246CJ", "G10019LZ", "G10486CT", "G10819WX", "G11314AS", "G14669DU", "G18647XP", "G23453IV", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G37509XX", "G38663NM", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G43089EG", "G48414YA", "G49018RC", "G49955PK", "G57776ZU", "G59626AS", "G59924QI", "G60033FS", "G62765YT", "G65184UU", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G79666IR", "G80075MS", "G80920RR", "G85282JO", "G85554PZ", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92050GC", "G01160VV", "G02528FI", "G05049YU", "G05724UK", "G06247RL", "G06356OH", "G08918WF", "G12261QD", "G12341GU", "G13131HA", "G14110OQ", "G20528HD", "G23719VF", "G24528MX", "G25079LO", "G25637MV", "G27126ED", "G27947YN", "G29545VG", "G30970QQ", "G33791AF", "G35029YA", "G35541EV", "G37399XV", "G37412TK", "G37818NZ", "G39188ZX", "G39471UU", "G40926MX", "G43223CG", "G43669FQ", "G43769HG", "G44753VC", "G47644PP", "G47702MW", "G49755GI", "G49906RN", "G50856PC", "G55132BD", "G57317CE", "G57776ZS", "G59536GA", "G60834IK", "G60967DT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G75568BH", "G76295SF", "G80479JV", "G83460ZZ", "G83646BJ", "G86182NS", "G88891KO", "G93718GY", "G95865ZB", "G96091TT", "G99679NM", "G04854VP", "G05962QB", "G17208MA", "G28622IK", "G49642SA", "G60923RB", "G61256FT", "G63136LV", "G77669RF", "G78787DI", "G92135MA", "G94470IW", "G99668VU", "G57321FI", "G04657PL", "G45395BF", "G45504EY", "G46691LC", "G51653BI", "G70418MS", "G84225JN", "G98611JV", "G43417UB", "G27391WQ", "G29068FM", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G10846ZT", "G15664MX", "G29184RN", "G31028YV", "G33416PL", "G40574BA", "G40834TG", "G41840AI", "G07810QS", "G13694XX", "G14972EH", "G16125XL", "G20210JR", "G26330YA", "G30221QT", "G30740WO", "G34989PA", "G37881RL", "G43734MM", "G44215PV", "G53075ES", "G56518TU", "G57888GL", "G58087IP", "G69521XL", "G70223PD", "G70888PK", "G72291OX", "G73430PD", "G75983OB", "G81637OR", "G82830MN", "G84452RH", "G86795LJ", "G90382BL", "G94665LC", "G81124ET", "G89827JR", "G90093AU", "G92275SC", "G01485JJ", "G03644CB", "G07755XJ", "G30769VJ", "G32788FZ", "G34617SM", "G37995HC", "G41882MT", "G45526EA", "G46503DX", "G47012YE", "G52890YB", "G58954YZ", "G64394MX", "G73968GN", "G83633GK", "G94831VI", "G95046LV", "G95177YH", "G49108TO" ], "uniprot_id": "P15144" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345092" }, { "confidence": "low", "disease": "White matter injury", "glycan_involvement": "MBP can be O-glycosylated; glycosylation may affect myelin stability.", "mechanism": "Damaged MBP indicates myelin injury, a feature of cSVD.", "protein": "MBP", "relationship_type": "biomarker", "source_pmcid": "PMC12345092" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "N-glycosylation of VCAM1 is critical for its function in cell adhesion.", "mechanism": "VCAM1-mediated leukocyte adhesion and BBB dysfunction contribute to neurovascular uncoupling and cognitive decline.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC12345092" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation at N219, N200, N192 regulates PD-L1 stability and degradation.", "mechanism": "PD-L1 promotes immune evasion by binding PD-1 on CD8+ T cells; high PD-L1 correlates with poor prognosis.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation regulates PD-L1 degradation.", "mechanism": "Emodin destabilizes PD-L1, enhancing anti-tumor immunity.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "medium", "disease": "Non-small cell lung cancer", "glycan_involvement": "N-glycosylation affects PD-L1 stability.", "mechanism": "PD-L1 expression is a target for immune checkpoint blockade.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation modulates PD-L1 function.", "mechanism": "PD-L1 expression correlates with immune evasion.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation influences PD-L1 degradation.", "mechanism": "PD-L1 is a biomarker for immune checkpoint therapy.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GSK-3\u03b2 binds nonglycosylated PD-L1 at N-glycosylation sites, leading to phosphorylation-dependent degradation.", "mechanism": "GSK-3\u03b2 promotes PD-L1 degradation, suppressing immune evasion and tumor growth.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "protective", "source_pmcid": "PMC12345107" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1, increasing its surface expression.", "mechanism": "High PD-L1 levels indicate poor prognosis and immune suppression.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "biomarker", "source_pmcid": "PMC12345107" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation regulates PD-L1 recycling and degradation.", "mechanism": "PD-L1/PD-1 axis causes CD8+ T cell exhaustion and tumor immune evasion.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "causal", "source_pmcid": "PMC12345107" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Emodin promotes degradation of glycosylated PD-L1.", "mechanism": "Emodin accelerates PD-L1 proteasomal degradation via GSK-3\u03b2, enhancing anti-tumor immunity.", "protein": "PD-L1 (CD274/B7-H1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GSK-3\u03b2 targets nonglycosylated PD-L1 at N-glycosylation sites for degradation.", "mechanism": "Emodin upregulates GSK-3\u03b2, which increases PD-L1 degradation and anti-tumor immune response.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345107" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation confers bioactivity and solubility.", "mechanism": "Traditional use for glycemic control; glycosides may modulate glucose metabolism.", "protein": "Glycosides (cardiac glycosides)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345324" }, { "confidence": "high", "disease": "Oxidative stress-related pathologies", "glycan_involvement": "Sugar moieties enhance radical scavenging and bioavailability.", "mechanism": "Antioxidant activity reduces oxidative damage.", "protein": "Flavonoid glycosides", "relationship_type": "protective", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "Glycosylation affects stability and function.", "mechanism": "Serum albumin levels used to assess liver function after extract administration.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Renal injury", "glycan_involvement": "Includes glycoproteins; glycosylation status may change in disease.", "mechanism": "Serum protein levels monitored for nephrotoxicity.", "protein": "Total protein (serum)", "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "N-glycosylation modulates enzyme activity.", "mechanism": "ALP levels indicate liver function; no toxicity observed.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "Glycosylation may affect serum half-life.", "mechanism": "ALT levels used to detect hepatocellular damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "Glycosylation influences enzyme stability.", "mechanism": "AST levels used to assess liver toxicity.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation essential for activity and membrane interaction.", "mechanism": "Saponins exhibit anti-inflammatory effects.", "protein": "Saponins (glycosylated triterpenes)", "relationship_type": "protective", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Diabetic wound healing", "glycan_involvement": "Glycosylation increases solubility and tissue penetration.", "mechanism": "Promote wound healing via antioxidant and antimicrobial effects.", "protein": "Phenolic glycosides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "Conjugation involves glycosylation-like glucuronidation.", "mechanism": "Monitored to assess liver function after extract exposure.", "protein": "Direct bilirubin (conjugated)", "relationship_type": "biomarker", "source_pmcid": "PMC12345324" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation affects CagA's interaction with host cells.", "mechanism": "Promotes cancer onset via genotoxicity and inflammation during gut dysbiosis.", "protein": "CagA protein", "relationship_type": "causal", "source_pmcid": "PMC12345372" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "LPS glycan moiety is recognized by immune receptors.", "mechanism": "Activates TLR4, triggers NF-kB, induces inflammatory gene expression and epigenetic changes.", "protein": "Lipopolysaccharide (LPS)", "relationship_type": "causal", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "PARP1 glycosylation may affect DNA repair and inflammation.", "mechanism": "Microcystin toxin increases PARP1, promoting inflammation and carcinogenesis.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Histone glycosylation modulates chromatin and gene expression.", "mechanism": "Phosphorylation/glycosylation changes (e.g., H3S10) linked to carcinogenesis and microbial invasion.", "protein": "Histone H3", "relationship_type": "causal", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "Pulmonary infections", "glycan_involvement": "Glycosylation affects toxin activity and host interaction.", "mechanism": "Streptococcus pneumoniae toxin disrupts lung epithelium, may contribute to carcinogenesis.", "protein": "Pneumolysin", "protein_enriched": { "function": "", "gene_name": "amy1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0C1B3" }, "relationship_type": "causal", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "Vesicle glycoproteins mediate cell targeting and immune modulation.", "mechanism": "Internalized by lung cancer cells, modulate immunotherapy response.", "protein": "Bifidobacterium-derived extracellular vesicles (Bif.BEVs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345372" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "SCFAs are products of glycan fermentation by gut microbes.", "mechanism": "SCFAs (e.g., butyrate) inhibit HDAC, reduce inflammation, promote antitumor immunity.", "protein": "Short-chain fatty acids (SCFAs)", "relationship_type": "protective", "source_pmcid": "PMC12345372" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Derived from microbial fermentation of dietary glycans.", "mechanism": "HDAC inhibition, anti-inflammatory, promotes apoptosis of cancer cells.", "protein": "Butyrate", "relationship_type": "protective", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "Epigenetic dysregulation", "glycan_involvement": "Folate is a methyl donor in glycan-linked epigenetic regulation.", "mechanism": "Microbial folate affects DNA methylation, modulates gene expression.", "protein": "Folate", "relationship_type": "protective", "source_pmcid": "PMC12345372" }, { "confidence": "medium", "disease": "Epigenetic dysregulation", "glycan_involvement": "Biotin is attached to histones via glycan linkages.", "mechanism": "Biotinylation of histones regulates DNA repair, cell cycle, and gene silencing.", "protein": "Biotin", "relationship_type": "protective", "source_pmcid": "PMC12345372" }, { "confidence": "high", "disease": "Weaning stress-induced intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation critical for mucin function and barrier properties.", "mechanism": "Upregulation of MUC2 restores mucus layer, enhancing barrier integrity and preventing pathogen invasion.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Weaning stress-induced intestinal barrier dysfunction", "glycan_involvement": "Glycosylation modulates tight junction assembly and stability.", "mechanism": "Upregulation strengthens tight junctions, reducing intestinal permeability.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Weaning stress-induced intestinal barrier dysfunction", "glycan_involvement": "Glycosylation affects claudin localization and function.", "mechanism": "Increased expression improves paracellular barrier, limiting leakage.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "medium", "disease": "Weaning stress-induced intestinal barrier dysfunction", "glycan_involvement": "Glycosylation may influence protein-protein interactions in junctions.", "mechanism": "Upregulation supports tight junction complex formation.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "N-glycosylation essential for IgA secretion and function.", "mechanism": "Elevated IgA enhances mucosal immunity, reducing diarrhea incidence.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "N-glycosylation required for IgM multimerization and activity.", "mechanism": "Increased IgM improves immune defense against pathogens.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation modulates cytokine stability and secretion.", "mechanism": "Elevated IL-1\u03b2 indicates inflammation; CAG reduces its levels, mitigating damage.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345433" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding and activity.", "mechanism": "High TNF-\u03b1 correlates with inflammation; CAG lowers TNF-\u03b1, reducing inflammatory response.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12345433" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation influences cytokine anti-inflammatory function.", "mechanism": "Increased IL-10 promotes anti-inflammatory effects, aiding barrier repair.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345433" }, { "confidence": "high", "disease": "Diarrhea", "glycan_involvement": "O-glycosylation essential for mucin gel formation.", "mechanism": "Restored MUC2 expression thickens mucus layer, preventing diarrhea.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "protective", "source_pmcid": "PMC12345433" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Insulin glycosylation affects stability and receptor binding.", "mechanism": "CNT supplementation increases serum insulin, potentially improving insulin sensitivity and glucose uptake.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "protective", "source_pmcid": "PMC12345455" }, { "confidence": "medium", "disease": "Growth hormone deficiency", "glycan_involvement": "GH glycosylation modulates secretion and activity.", "mechanism": "CNT supplementation elevates serum GH, supporting lactation and nutrient partitioning.", "protein": "Growth hormone (Somatotropin)", "relationship_type": "protective", "source_pmcid": "PMC12345455" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "LDH glycosylation influences enzyme stability.", "mechanism": "Lower LDH activity in CNT groups indicates reduced liver cell damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345455" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "AST glycosylation affects enzyme activity.", "mechanism": "Reduced AST activity in CNT groups reflects improved liver function.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345455" }, { "confidence": "medium", "disease": "Immune deficiency (low IgG)", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "CNT increases IgG in colostrum, enhancing immune protection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12345455" }, { "confidence": "high", "disease": "Milk protein deficiency", "glycan_involvement": "Casein glycosylation affects micelle formation and digestibility.", "mechanism": "CNT increases milk protein content, improving nutritional quality.", "protein": "Milk proteins (caseins)", "relationship_type": "protective", "source_pmcid": "PMC12345455" }, { "confidence": "medium", "disease": "Milk protein deficiency", "glycan_involvement": "Microbial glycoproteins may influence rumen fermentation.", "mechanism": "CNT stimulates Succinivibrionaceae, correlating with higher milk protein.", "protein": "Succinivibrionaceae-associated proteins", "relationship_type": "protective", "source_pmcid": "PMC12345455" }, { "confidence": "medium", "disease": "Milk fat depression", "glycan_involvement": "Microbial glycoproteins affect fatty acid metabolism.", "mechanism": "CNT reduces Butyrivibrio abundance, associated with lower milk fat.", "protein": "Butyrivibrio-associated proteins", "relationship_type": "causal", "source_pmcid": "PMC12345455" }, { "confidence": "low", "disease": "Milk fat depression", "glycan_involvement": "SREBP1 glycosylation regulates transcriptional activity.", "mechanism": "CNT may inhibit SREBP1 signaling, reducing milk fat synthesis.", "protein": "Sterol response element-binding protein 1 (SREBP1)", "relationship_type": "causal", "source_pmcid": "PMC12345455" }, { "confidence": "low", "disease": "Oxidative stress", "glycan_involvement": "Albumin glycosylation modulates antioxidant capacity.", "mechanism": "Albumin levels unchanged, indicating stable antioxidant status with CNT.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345455" }, { "confidence": "high", "disease": "Embryonic developmental failure", "glycan_involvement": "Glycosylation stabilizes HSP70 structure and function under stress.", "mechanism": "HSP70 upregulation mitigates heat-induced protein misfolding and supports embryo survival.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "protective", "source_pmcid": "PMC12345539" }, { "confidence": "high", "disease": "Impaired steroidogenesis", "glycan_involvement": "N-glycosylation required for ER localization and chaperone activity.", "mechanism": "GRP78 upregulation marks ER stress in granulosa cells, leading to reduced steroid hormone production.", "protein": "GRP78", "relationship_type": "biomarker", "source_pmcid": "PMC12345539" }, { "confidence": "high", "disease": "Impaired steroidogenesis", "glycan_involvement": "Glycosylation affects LHR cell surface expression and ligand binding.", "mechanism": "Heat stress induces MVK-LHR complex formation, degrading LHR mRNA and reducing estradiol synthesis.", "protein": "LHR", "relationship_type": "causal", "source_pmcid": "PMC12345539" }, { "confidence": "medium", "disease": "Heat stress-induced infertility", "glycan_involvement": "Glycosylation modulates COX2 stability and activity.", "mechanism": "COX2 expression is altered under heat stress, affecting prostaglandin synthesis and ovulation.", "protein": "COX2", "relationship_type": "biomarker", "source_pmcid": "PMC12345539" }, { "confidence": "medium", "disease": "Apoptosis of granulosa cells", "glycan_involvement": "Glycosylation influences XIAP anti-apoptotic function.", "mechanism": "XIAP upregulation inhibits caspase-mediated apoptosis under heat stress.", "protein": "XIAP", "protein_enriched": { "function": "Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as", "gene_name": "XIAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P98170" }, "relationship_type": "protective", "source_pmcid": "PMC12345539" }, { "confidence": "medium", "disease": "Apoptosis of granulosa cells", "glycan_involvement": "Glycosylation affects BCL-2 stability and anti-apoptotic activity.", "mechanism": "BCL-2 expression counteracts heat-induced apoptosis in ovarian cells.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12345539" }, { "confidence": "medium", "disease": "Apoptosis of granulosa cells", "glycan_involvement": "Glycosylation may regulate caspase-3 activation and localization.", "mechanism": "Heat stress activates caspase-3, promoting apoptosis and reducing cell viability.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "causal", "source_pmcid": "PMC12345539" }, { "confidence": "high", "disease": "Impaired steroidogenesis", "glycan_involvement": "Glycosylation required for STAR mitochondrial targeting.", "mechanism": "Heat stress downregulates STAR, reducing cholesterol transport and steroid hormone synthesis.", "protein": "STAR", "relationship_type": "causal", "source_pmcid": "PMC12345539" }, { "confidence": "high", "disease": "Impaired steroidogenesis", "glycan_involvement": "Glycosylation modulates aromatase activity.", "mechanism": "Heat stress reduces CYP19A1 expression, limiting estradiol production.", "protein": "CYP19A1", "relationship_type": "causal", "source_pmcid": "PMC12345539" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "N-glycosylation essential for ER chaperone function.", "mechanism": "GRP94 upregulation indicates ER stress and oxidative imbalance in granulosa cells.", "protein": "GRP94", "relationship_type": "biomarker", "source_pmcid": "PMC12345539" }, { "confidence": "high", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may regulate FAS stability and activity.", "mechanism": "Upregulation promotes hepatic triglyceride synthesis and fat accumulation.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "high", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation affects nuclear translocation and transcriptional activity.", "mechanism": "Upregulation drives lipogenic gene expression, leading to hepatic steatosis.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Increased ACC enhances fatty acid synthesis, contributing to liver fat accumulation.", "protein": "ACC", "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation influences ligand binding and stability.", "mechanism": "Elevated FABP reflects increased fatty acid transport in steatotic liver.", "protein": "FABP", "relationship_type": "biomarker", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may affect membrane localization.", "mechanism": "Upregulation increases triglyceride assembly in hepatocytes.", "protein": "GPAT1", "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may regulate transcriptional activity.", "mechanism": "Promotes expression of lipogenic genes under high carbohydrate conditions.", "protein": "ChREBP1", "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may affect receptor function.", "mechanism": "Activates lipogenic gene transcription, exacerbating hepatic lipid accumulation.", "protein": "LXR\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "high", "disease": "Liver Inflammation", "glycan_involvement": "Glycosylation is essential for ligand recognition and signaling.", "mechanism": "Upregulation triggers NF-\u03baB pathway, promoting inflammatory cytokine production.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "high", "disease": "Liver Inflammation", "glycan_involvement": "Glycosylation modulates secretion and receptor binding.", "mechanism": "Elevated IL-6 indicates hepatic inflammatory response.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345561" }, { "confidence": "medium", "disease": "Fatty Liver Syndrome (FLS)", "glycan_involvement": "Glycosylation may affect nuclear import and activity.", "mechanism": "Regulates cholesterol biosynthesis, contributing to lipid dysregulation.", "protein": "SREBP-2", "relationship_type": "causal", "source_pmcid": "PMC12345561" }, { "confidence": "high", "disease": "Acute physiological stress", "glycan_involvement": "Cortisol is transported by glycoprotein corticosteroid-binding globulin; glycosylation affects its half-life.", "mechanism": "Cortisol elevation indicates HPA axis activation in response to acute stress.", "protein": "Cortisol", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "high", "disease": "Acute physiological stress", "glycan_involvement": "ACTH is a glycoprotein; glycosylation modulates its stability and receptor interaction.", "mechanism": "ACTH elevation reflects pituitary response to stress, stimulating cortisol release.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "medium", "disease": "Exercise-induced muscle damage", "glycan_involvement": "LDH is glycosylated; glycosylation may affect enzyme stability in circulation.", "mechanism": "Elevated LDH in plasma indicates muscle cell membrane damage due to intense exercise.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "high", "disease": "Exercise-induced muscle damage", "glycan_involvement": "CK is not a glycoprotein; no glycan involvement.", "mechanism": "CK elevation in blood is a direct marker of muscle membrane disruption.", "protein": "CK", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "medium", "disease": "Dehydration", "glycan_involvement": "Hemoglobin is glycosylated; glycosylation status can affect oxygen affinity.", "mechanism": "Increased hemoglobin concentration reflects hemoconcentration due to fluid loss.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "medium", "disease": "Acute physiological stress", "glycan_involvement": "Glycosylation of surface proteins modulates cell trafficking and immune response.", "mechanism": "Stress leukogram (increased WBCs) is mediated by redistribution of leukocytes, involving cell surface glycoproteins.", "protein": "White blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "medium", "disease": "Meat quality defects", "glycan_involvement": "Glycosylation may affect LDH stability in tissue and plasma.", "mechanism": "High LDH post-exercise is associated with poor meat quality due to muscle damage.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "medium", "disease": "Meat quality defects", "glycan_involvement": "CK is not glycosylated.", "mechanism": "Elevated CK correlates with muscle injury and subsequent meat quality reduction.", "protein": "CK", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "low", "disease": "Chronic muscle lesions", "glycan_involvement": "Glycosylation affects ACTH bioactivity.", "mechanism": "Repeated stress and ACTH elevation may contribute to chronic muscle pathology.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "low", "disease": "Metabolic acidosis", "glycan_involvement": "Transport and clearance of cortisol are influenced by glycoprotein carriers.", "mechanism": "Cortisol elevation is part of the adaptive response to metabolic acidosis induced by intense exercise.", "protein": "Cortisol", "relationship_type": "biomarker", "source_pmcid": "PMC12345578" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Collagen is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Increased synthesis by hepatic stellate cells leads to excess ECM deposition and fibrosis.", "protein": "Type I collagen (COL1A1)", "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Integrins are N-glycosylated; glycosylation modulates ligand binding and signaling.", "mechanism": "Insulin stimulates \u03b15\u03b21 integrin expression and signaling, promoting collagen synthesis in HSCs.", "protein": "\u03b15\u03b21 integrin", "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "CEACAM1 is a glycoprotein; glycosylation affects its cell surface expression and function.", "mechanism": "Mutations impair hepatic insulin clearance, causing hyperinsulinemia and insulin resistance.", "protein": "CEACAM1", "protein_enriched": { "function": "Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and also function", "gene_name": "CEACAM1", "glycan_count": 47, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22572EH", "G49108TO", "G57776ZS", "G80075MS", "G92275SC", "G00912UN", "G05724UK", "G06110VR", "G07246CJ", "G10819WX", "G14669DU", "G27947YN", "G28681TP", "G39188ZX", "G40926MX", "G49906RN", "G59626AS", "G70441OD", "G70619PT", "G79666IR", "G80920RR", "G86880BF", "G87661QW", "G41071NU", "G42124LM", "G23984SE", "G27058EU", "G75983OB", "G83229XP", "G84452RH", "G01650EU", "G02815KT", "G11870QZ", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G43089EG", "G59924QI", "G62765YT", "G64527OM", "G84225JN", "G92050GC", "G92406TI", "G95865ZB", "G25418HZ" ], "uniprot_id": "P13688" }, "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation of collagen influences ECM assembly.", "mechanism": "Hyperinsulinemia increases collagen synthesis, contributing to fibrosis in MASLD.", "protein": "Type I collagen (COL1A1)", "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation of integrin modulates its activation.", "mechanism": "Blocking \u03b15\u03b21 integrin signaling reduces insulin-induced collagen synthesis and fibrosis.", "protein": "\u03b15\u03b21 integrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345635" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation status may affect detectability and function.", "mechanism": "Elevated hepatic collagen is a marker of advanced fibrosis in MASH.", "protein": "Type I collagen (COL1A1)", "relationship_type": "biomarker", "source_pmcid": "PMC12345635" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Glycosylation regulates integrin function.", "mechanism": "Integrin-mediated signaling drives HSC activation and fibrogenesis in chronic liver injury.", "protein": "\u03b15\u03b21 integrin", "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects CEACAM1-mediated insulin clearance.", "mechanism": "CEACAM1 mutation leads to hyperinsulinemia, indirectly promoting fibrosis.", "protein": "CEACAM1", "protein_enriched": { "function": "Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and also function", "gene_name": "CEACAM1", "glycan_count": 47, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22572EH", "G49108TO", "G57776ZS", "G80075MS", "G92275SC", "G00912UN", "G05724UK", "G06110VR", "G07246CJ", "G10819WX", "G14669DU", "G27947YN", "G28681TP", "G39188ZX", "G40926MX", "G49906RN", "G59626AS", "G70441OD", "G70619PT", "G79666IR", "G80920RR", "G86880BF", "G87661QW", "G41071NU", "G42124LM", "G23984SE", "G27058EU", "G75983OB", "G83229XP", "G84452RH", "G01650EU", "G02815KT", "G11870QZ", "G22310AV", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G43089EG", "G59924QI", "G62765YT", "G64527OM", "G84225JN", "G92050GC", "G92406TI", "G95865ZB", "G25418HZ" ], "uniprot_id": "P13688" }, "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "FAK is glycosylated; modification may affect signaling.", "mechanism": "Insulin-induced FAK phosphorylation downstream of \u03b15\u03b21 integrin promotes collagen synthesis.", "protein": "Focal adhesion kinase (FAK)", "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "IRS1 is a glycoprotein; glycosylation may affect stability.", "mechanism": "IRS1 mediates insulin signaling in HSCs, but collagen synthesis is PI3K-independent.", "protein": "IRS1", "protein_enriched": { "function": "Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:75410", "gene_name": "IRS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35568" }, "relationship_type": "causal", "source_pmcid": "PMC12345635" }, { "confidence": "high", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Wnt3a is a secreted glycoprotein; glycosylation is required for secretion and receptor binding.", "mechanism": "Activates canonical Wnt/\u03b2-catenin signaling, increasing proliferation and self-renewal of leukemic cells.", "protein": "Wnt3a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/L", "gene_name": "WNT3A", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ", "G85146YR", "G32577BC" ], "uniprot_id": "P56704" }, "relationship_type": "causal", "source_pmcid": "PMC12345650" }, { "confidence": "high", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for function.", "mechanism": "Overexpressed in E2A-PBX1+ B-ALL; promotes survival and drug resistance; knockdown induces apoptosis.", "protein": "Wnt16b", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is", "gene_name": "WNT16", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBV4" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12345650" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for secretion.", "mechanism": "Promotes migration and invasion of T-ALL cells via non-canonical Wnt/Ca2+ pathway.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12345650" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for function.", "mechanism": "Overexpressed in AC133+ AML stem/progenitor cells; promotes stemness and proliferation.", "protein": "Wnt10b", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12345650" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for secretion.", "mechanism": "Overexpressed; induces aberrant methylation, enhances proliferation, reduces apoptosis.", "protein": "Wnt2b", "protein_enriched": { "function": "Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase which sumoylates CHD3/Mi2-alpha, causing its release from DNA (PubMed:27068747). This results in suppression of CHD3/Mi2-alpha trans", "gene_name": "ZBED1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O96006" }, "relationship_type": "causal", "source_pmcid": "PMC12345650" }, { "confidence": "high", "disease": "ALL (B-ALL and T-ALL)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Stabilization and nuclear translocation drive transcription of oncogenic targets (Myc, survivin, etc.), promoting leukemogenesis and drug resistance.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12345650" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "Cell surface glycoproteins mediating Wnt ligand signaling; targeting FZD inhibits Wnt pathway and reduces leukemia cell survival.", "protein": "Frizzled (FZD) receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345650" }, { "confidence": "medium", "disease": "ALL", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Co-receptors for Wnt ligands; overexpression linked to ALL pathogenesis and disease severity.", "protein": "LRP5/6", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345650" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "Secreted glycoprotein; glycosylation required for function.", "mechanism": "Amplifies Wnt signaling via LGR4; targeting RSPO-LGR4 axis disrupts LSC self-renewal.", "protein": "RSPO (R-spondin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345650" }, { "confidence": "high", "disease": "AML", "glycan_involvement": "Glycosylation creates AC133 epitope, critical for stem cell identification.", "mechanism": "Glycosylation-dependent epitope marks stem/progenitor cells with high WNT10B expression.", "protein": "CD133 (AC133)", "relationship_type": "biomarker", "source_pmcid": "PMC12345650" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "GD2 is a sialylated glycolipid; its glycan structure is essential for antibody recognition.", "mechanism": "GD2 is highly expressed on neuroblastoma cells and targeted by monoclonal antibodies for immunotherapy.", "protein": "GD2 (disialoganglioside)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "DB is an IgG1 glycoprotein; Fc glycosylation is required for effector functions.", "mechanism": "DB binds GD2 and mediates ADCC and CDC, leading to tumor cell killing.", "protein": "Dinutuximab beta (DB)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "NAXI is an IgG1 glycoprotein; Fc glycosylation is required for effector functions.", "mechanism": "NAXI binds GD2 with higher affinity, mediates ADCC and CDC, but is more susceptible to target-mediated drug disposition (TMDD).", "protein": "Naxitamab (NAXI)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "Relapsed/refractory neuroblastoma", "glycan_involvement": "Glycan structure of GD2 is essential for antibody binding.", "mechanism": "GD2 remains a target in relapsed/refractory disease for antibody-based therapies.", "protein": "GD2 (disialoganglioside)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "Relapsed/refractory neuroblastoma", "glycan_involvement": "Fc glycosylation of DB is necessary for ADCC/CDC.", "mechanism": "DB is used in maintenance and relapsed/refractory settings, showing higher ADCC potency than NAXI.", "protein": "Dinutuximab beta (DB)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "Relapsed/refractory neuroblastoma", "glycan_involvement": "Fc glycosylation of NAXI is necessary for ADCC/CDC.", "mechanism": "NAXI is approved for relapsed/refractory neuroblastoma, but its efficacy is reduced by TMDD and soluble GD2.", "protein": "Naxitamab (NAXI)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12345752" }, { "confidence": "medium", "disease": "High-risk neuroblastoma", "glycan_involvement": "CD64 is a glycoprotein; glycosylation may affect Fc binding.", "mechanism": "CD64+ monocytes internalize NAXI more than DB, contributing to TMDD and reduced antibody availability.", "protein": "CD64 (Fc\u03b3RI)", "protein_enriched": { "function": "High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses", "gene_name": "Fcgr1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G16125XL" ], "uniprot_id": "P26151" }, "relationship_type": "modulator of therapy", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "Glycan structure is critical for antibody recognition.", "mechanism": "GD2 expression distinguishes neuroblastoma cells from normal tissue, enabling targeted therapy.", "protein": "GD2 (disialoganglioside)", "relationship_type": "biomarker", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "Soluble glycan structure competes for antibody binding.", "mechanism": "Soluble GD2 acts as an antigen sink, reducing NAXI binding and ADCC potency.", "protein": "Soluble GD2", "relationship_type": "modulator of therapy", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "High-risk neuroblastoma", "glycan_involvement": "Glycosylation affects Fc effector function and pharmacokinetics.", "mechanism": "DB's intermediate affinity and glycosylation pattern result in less TMDD and higher functional potency.", "protein": "Dinutuximab beta (DB)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12345752" }, { "confidence": "high", "disease": "Milk allergy", "glycan_involvement": "Glycosylation affects allergenicity and detection", "mechanism": "\u03b1-lactalbumin is a major milk allergen detected by aptamers for food safety", "protein": "\u03b1-lactalbumin", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated S protein modulates immune evasion and aptamer binding", "mechanism": "Aptamers target S protein for detection and potential neutralization", "protein": "SARS-CoV-2 S protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345920" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences RBD structure and aptamer recognition", "mechanism": "Aptamers detect RBD for diagnostic purposes", "protein": "Receptor-binding domain (RBD) of SARS-CoV-2", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Diabetes (microangiopathy)", "glycan_involvement": "Advanced glycation/glycosylation products accumulate in diabetes", "mechanism": "Detection of glycosylated proteins reflects glycation status in diabetes", "protein": "Late glycosylation end-product", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may affect thrombin function and aptamer binding", "mechanism": "Aptamers modulate thrombin activity for anticoagulation", "protein": "Thrombin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Oral health disorders", "glycan_involvement": "Glycosylation influences enzyme stability and detection", "mechanism": "Aptamers detect salivary amylase as a marker in food and oral health", "protein": "Salivary amylase", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Surface glycosylation patterns are cancer-specific", "mechanism": "Aptamers detect exosome glycoproteins for cancer diagnostics", "protein": "Exosome surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Foot-and-mouth disease", "glycan_involvement": "Viral glycosylation affects host interaction and detection", "mechanism": "Aptamers detect viral glycoproteins for early diagnosis", "protein": "Foot-and-mouth disease virus glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Avian influenza", "glycan_involvement": "Glycosylation modulates antigenicity and detection", "mechanism": "Aptamers detect hemagglutinin for surveillance in food products", "protein": "Avian influenza virus hemagglutinin", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "Glycosylation affects viral stability and immune recognition", "mechanism": "Aptamers detect viral capsid glycoproteins in contaminated food", "protein": "Hepatitis A virus capsid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12345920" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Non-enzymatic glycation of lysine residues forms CML.", "mechanism": "AGEs like CML induce oxidative stress and damage nerve cells, contributing to diabetes pathogenesis.", "protein": "N\u03b5-carboxymethyl-lysine (CML)", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Glycation of proteins by CML disrupts neuronal function.", "mechanism": "AGE accumulation damages nerve cells, leading to neurodegenerative changes.", "protein": "N\u03b5-carboxymethyl-lysine (CML)", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "high", "disease": "Oxidative stress-related disorders", "glycan_involvement": "AGE-modified proteins alter redox balance.", "mechanism": "CML induces oxidative stress in tissues.", "protein": "N\u03b5-carboxymethyl-lysine (CML)", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Non-enzymatic glycation of lysine residues forms CEL.", "mechanism": "CEL, as an AGE, accumulates and contributes to diabetic complications.", "protein": "N\u03b5-carboxyethyl-lysine (CEL)", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Oxidative stress-related disorders", "glycan_involvement": "Polymeric glycoprotein structures with antioxidant properties.", "mechanism": "Melanoidins exhibit antioxidant activity, scavenging free radicals.", "protein": "Melanoidins", "relationship_type": "protective", "source_pmcid": "PMC12345924" }, { "confidence": "high", "disease": "Protein malnutrition", "glycan_involvement": "Early glycation of protein amino groups.", "mechanism": "Initial glycation reduces lysine bioavailability and protein digestibility.", "protein": "Schiff base/Amadori products", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Genotoxicity", "glycan_involvement": "Glycation by reactive dicarbonyls.", "mechanism": "GO-derived AGEs contribute to DNA damage and genotoxicity.", "protein": "Glyoxal (GO)-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Mutagenicity", "glycan_involvement": "Protein glycation by MGO.", "mechanism": "MGO-derived AGEs induce mutations in genetic material.", "protein": "Methylglyoxal (MGO)-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Protein malnutrition", "glycan_involvement": "Glycation of lysine residues in casein.", "mechanism": "Maillard reaction with casein reduces lysine availability, lowering nutritional value.", "protein": "Casein", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "Non-enzymatic glycation of lysine side chains.", "mechanism": "AGEs formed on lysine residues (e.g., CML) are neurotoxic and linked to nerve damage.", "protein": "Lysine-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12345924" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "CS is covalently attached to core proteins, forming CSPGs; sulfation pattern modulates interaction with CD44.", "mechanism": "CS-based nanoplatforms target CD44 on tumor cells for drug delivery, enhancing cytotoxicity and reducing metastasis.", "protein": "Chondroitin sulfate proteoglycans (CSPGs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "CD44 binds CS chains; glycosylation of CD44 may affect ligand binding.", "mechanism": "CD44 is overexpressed on breast cancer cells; CS-decorated nanoparticles bind CD44, promoting targeted drug delivery.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "CS mimics natural ligands for E-selectin, facilitating adhesion and uptake.", "mechanism": "CS-based micelles target both CD44 and E-selectin, increasing cytotoxicity and uptake in tumor cells.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Multidrug-resistant breast cancer", "glycan_involvement": "P-glycoprotein is N-glycosylated; glycosylation affects stability and function.", "mechanism": "CS-based nanoparticles co-deliver P-gp inhibitors and chemotherapeutics, overcoming drug resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "GalNAc-T catalyzes O-glycosylation; CS targeting exploits glycan recognition.", "mechanism": "CS-modified nanoparticles target the Golgi apparatus via interaction with GalNAc-T, disrupting ECM and inhibiting tumor growth.", "protein": "GalNAc-T (N-acetylgalactosaminyltransferases)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Lactoferrin is N-glycosylated; glycosylation may affect nanoparticle interaction.", "mechanism": "Layer-by-layer CS/LF-coated nanoparticles enhance lung cancer targeting and reduce off-target toxicity.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Cathepsin B is glycosylated; glycosylation affects enzyme stability.", "mechanism": "CS-drug conjugates with cathepsin B-cleavable linkers enable tumor-specific drug release.", "protein": "Cathepsin B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "CS-protein conjugation enables targeting via glycan recognition.", "mechanism": "CS-anchored nanocapsules target macrophages for immunotherapy and chemotherapy.", "protein": "Chondroitin sulfate proteoglycans (CSPGs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Dry eye disease", "glycan_involvement": "CS-protein conjugates enhance mucoadhesion via glycan interactions.", "mechanism": "CS-based nanocarriers prolong drug retention and relieve dry eye symptoms.", "protein": "Chondroitin sulfate proteoglycans (CSPGs)", "relationship_type": "protective", "source_pmcid": "PMC12345942" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "CS modification enables CD44-mediated uptake.", "mechanism": "CS-modified dendrimers deliver miR-34a, inhibiting tumor growth and inducing apoptosis.", "protein": "PAMAM dendrimer-CS conjugate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345942" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSMA is a glycoprotein; glycosylation is required for its proper folding, stability, and cell surface localization.", "mechanism": "PSMA is significantly overexpressed in prostate cancer cells compared to normal tissue, enabling its use for molecular imaging and diagnosis.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation supports PSMA's extracellular domain conformation, facilitating ligand binding.", "mechanism": "PSMA is targeted by imaging agents and therapeutics (e.g., 68Ga-PSMA-11, 177Lu-PSMA-617, ACUPA-based probes) for diagnosis and treatment.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345944" }, { "confidence": "high", "disease": "Metastatic castration-resistant prostate cancer (mCRPC)", "glycan_involvement": "Glycosylation maintains PSMA's surface expression, critical for effective targeting.", "mechanism": "PSMA is targeted by radioligand therapies (e.g., 177Lu-PSMA-617) in mCRPC.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345944" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may influence PSMA stability and detection in tissue assays.", "mechanism": "High PSMA expression is associated with lower disease-free survival (DFS) in prostate cancer patients.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "prognostic_biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "medium", "disease": "Neuroendocrine prostate cancer (NEPC)", "glycan_involvement": "Loss of glycosylated PSMA correlates with aggressive, dedifferentiated states.", "mechanism": "PSMA expression declines in NEPC, reflecting disease progression and dedifferentiation.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "medium", "disease": "Double-negative prostate cancer (DNPC)", "glycan_involvement": "Reduced glycosylated PSMA on cell surface in DNPC.", "mechanism": "PSMA expression is low in DNPC, indicating loss of typical prostate lineage markers.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation ensures PSMA's extracellular accessibility for probe binding.", "mechanism": "PSMA-targeted NIR-II probes enable high-contrast imaging for tumor detection and surgical guidance.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "diagnostic_biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may modulate PSMA's interaction with ligands and antibodies.", "mechanism": "PSMA expression correlates with clinical features such as stage, metastasis, and molecular subtype.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker", "source_pmcid": "PMC12345944" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "PC is a major membrane glycerophospholipid; glycosylation status affects membrane dynamics.", "mechanism": "Elevated hepatic PC levels in HFD-induced obesity; reduction after BSP intervention.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "biomarker", "source_pmcid": "PMC12345948" }, { "confidence": "high", "disease": "Liver Steatosis", "glycan_involvement": "PE glycosylation influences lipid droplet formation.", "mechanism": "PE accumulation promotes lipid droplet aggregation and liver injury.", "protein": "Phosphatidylethanolamine (PE)", "relationship_type": "causal", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "PS glycosylation modulates receptor activation.", "mechanism": "PS activates PPAR-\u03b1, enhancing \u03b2-oxidation and reducing lipid accumulation.", "protein": "Phosphatidylserine (PS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation of sphingolipids affects signaling pathways.", "mechanism": "SM and ceramide accumulation disrupts membrane fluidity and impairs insulin signaling.", "protein": "Sphingomyelin (SM)", "relationship_type": "causal", "source_pmcid": "PMC12345948" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "CEs are transported by glycoprotein-rich lipoproteins.", "mechanism": "Elevated hepatic CE levels in HFD; reduced by BSP, alleviating steatosis.", "protein": "Cholesteryl Ester (CE)", "relationship_type": "biomarker", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation of carnitine transporters affects CAR metabolism.", "mechanism": "CAR accumulation linked to mitochondrial dysfunction and impaired insulin signaling.", "protein": "Acylcarnitine (CAR)", "relationship_type": "biomarker", "source_pmcid": "PMC12345948" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "TG transport via glycoprotein-rich lipoproteins.", "mechanism": "Elevated hepatic TGs in HFD; negative correlation with Atopostipes and Jeotgalicoccus abundance after BSP.", "protein": "Triglyceride (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation regulates SCD1 stability and activity.", "mechanism": "SCD1 catalyzes FA synthesis, promoting TG formation and adiposity.", "protein": "Stearoyl-CoA Desaturase 1 (SCD1)", "protein_enriched": { "function": "Promotes adhesion of endothelial cells through interaction with the alpha-v/beta-3 integrin receptor. Inhibits formation of vascular-like structures. May be involved in regulation of vascular morphoge", "gene_name": "Edil3", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "O35474" }, "relationship_type": "causal", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates FAS enzymatic activity.", "mechanism": "FAS drives endogenous FA synthesis, contributing to TG accumulation.", "protein": "Fatty Acid Synthase (FAS)", "relationship_type": "causal", "source_pmcid": "PMC12345948" }, { "confidence": "medium", "disease": "Primary Biliary Cholangitis", "glycan_involvement": "PC glycosylation affects bile composition.", "mechanism": "PC levels associated with biliary disease and subclinical atherosclerosis.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "biomarker", "source_pmcid": "PMC12345948" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "O-glycosylation of MUC1 is essential for its immunogenicity and tumor-specific expression.", "mechanism": "MUC1-based AuNP vaccine enhances anti-tumor immune response and tumor suppression.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346115" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and affects its immune checkpoint function.", "mechanism": "AuNPs deliver siRNA or antibodies to silence/inhibit PD-L1, restoring T-cell activity and suppressing tumor growth.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346115" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "N-glycosylation modulates PD-1 surface expression and ligand binding.", "mechanism": "AuNPs combined with PD-1/PD-L1 inhibitors enhance T-cell activation and anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346115" }, { "confidence": "high", "disease": "Tumor angiogenesis", "glycan_involvement": "N-glycosylation required for VEGF secretion and receptor interaction.", "mechanism": "AuNPs block VEGF-VEGFR2 signaling, inhibiting angiogenesis and normalizing tumor vasculature.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346115" }, { "confidence": "medium", "disease": "Tumor angiogenesis", "glycan_involvement": "N-glycosylation affects CD31-mediated cell adhesion.", "mechanism": "CD31 used to assess vascular normalization after AuNP treatment in tumors.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12346115" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation modulates CD86 stability and immune signaling.", "mechanism": "Polysaccharide-coated AuNPs upregulate CD86 on DCs, enhancing T-cell activation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346115" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation required for CD80 surface expression.", "mechanism": "AuNPs increase CD80 expression on DCs, promoting anti-tumor immunity.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346115" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation influences CD40 ligand binding.", "mechanism": "AuNPs upregulate CD40 on DCs, facilitating T-cell priming.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346115" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "N-glycosylation critical for MHC II folding and peptide loading.", "mechanism": "AuNPs enhance MHC II expression, improving antigen presentation and T-cell response.", "protein": "MHC II", "relationship_type": "biomarker", "source_pmcid": "PMC12346115" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Dense N-glycosylation on gp120 mediates immune evasion and receptor binding.", "mechanism": "Mannose-coated AuNPs mimic gp120 glycans, block HIV entry, and stimulate DC maturation.", "protein": "gp120 (HIV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346115" }, { "confidence": "high", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "gD is a glycoprotein; glycosylation is required for proper folding and function", "mechanism": "gD is essential for HSV-1 entry, cell-to-cell spread, and second envelopment", "protein": "glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "HSV-1-induced blindness", "glycan_involvement": "gD glycosylation facilitates host cell interaction", "mechanism": "gD mediates viral entry into corneal cells, contributing to keratitis and potential blindness", "protein": "glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "HSV-1 encephalitis", "glycan_involvement": "glycosylation supports gD stability and trafficking", "mechanism": "gD enables neuroinvasion and spread within the CNS", "protein": "glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "HSV-1 keratitis", "glycan_involvement": "glycosylation required for receptor binding", "mechanism": "gD mediates infection of corneal epithelial cells", "protein": "glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "gH is glycosylated; glycosylation is important for function", "mechanism": "gH is required for membrane fusion during viral entry", "protein": "glycoprotein gH", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "gE is glycosylated; glycosylation affects trafficking", "mechanism": "gE is involved in cell-to-cell spread of HSV-1", "protein": "glycoprotein gE", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "affects trafficking of glycosylated viral proteins", "mechanism": "Rab5 regulates endosomal trafficking of viral glycoproteins; its inhibition impairs HSV-1 replication", "protein": "Rab5", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB5A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20339" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "regulates trafficking of glycosylated viral proteins", "mechanism": "Rab11 is essential for recycling endosome-mediated transport of viral glycoproteins for second envelopment and release", "protein": "Rab11", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346171" }, { "confidence": "high", "disease": "Herpes simplex virus type 1 infection", "glycan_involvement": "glycosylation status of gD may affect its trafficking and retention", "mechanism": "PC treatment causes intracellular accumulation of gD, blocking viral assembly and release", "protein": "glycoprotein gD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346171" }, { "confidence": "medium", "disease": "HSV-1 in immunocompromised patients", "glycan_involvement": "glycosylation supports immune evasion and infectivity", "mechanism": "gD is required for viral spread and pathogenesis in vulnerable hosts", "protein": "glycoprotein gD", "relationship_type": "causal", "source_pmcid": "PMC12346171" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AR is a glycoprotein; glycosylation may affect stability and localization, but not directly discussed.", "mechanism": "AR upregulates cell cycle and proliferation pathways, driving HCC progression and sexual dimorphism.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AR-SVs retain glycoprotein features; glycosylation may affect variant function.", "mechanism": "High AR-SV expression correlates with reduced overall survival and increased tumor aggressiveness.", "protein": "AR Splice Variants (AR-SVs)", "relationship_type": "causal", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may modulate AR stability; not directly discussed.", "mechanism": "AR and AR-SVs drive castration-resistant prostate cancer; niclosamide reduces AR-SV protein.", "protein": "Androgen Receptor (AR)", "protein_enriched": { "function": "Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849).", "gene_name": "AR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10275" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-L1 is heavily N-glycosylated, which regulates its stability and immune evasion.", "mechanism": "PD-L1 is targeted by immune checkpoint inhibitors; niclosamide inhibits STAT3-mediated PD-L1 expression.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "STAT3 is a glycoprotein; glycosylation may affect function.", "mechanism": "STAT3 is activated in HCC; niclosamide inhibits IL-6-mediated STAT3 phosphorylation.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NF-\u03baB subunits can be glycosylated, affecting nuclear translocation.", "mechanism": "NF-\u03baB signaling is oncogenic in HCC; niclosamide inhibits NF-\u03baB activation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "KRAS can be O-glycosylated, affecting membrane localization.", "mechanism": "KRAS signaling is upregulated in HCC; niclosamide inhibits KRAS pathway.", "protein": "KRAS", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "VEGF-A is N-glycosylated, which is critical for secretion and function.", "mechanism": "VEGF-A promotes angiogenesis in HCC; targeted by bevacizumab.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CTLA-4 is N-glycosylated, affecting cell surface expression.", "mechanism": "CTLA-4 is targeted by immune checkpoint inhibitors (tremelimumab) in HCC.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation of PD-L1 is essential for immune evasion.", "mechanism": "PD-L1 expression is regulated by STAT3; niclosamide inhibits PD-L1 via STAT3.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346198" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "APA is a glycoprotein; glycosylation may affect membrane localization and enzymatic activity.", "mechanism": "Reduced protein expression in ccRCC tumor tissue compared to normal kidney; involved in RAAS and blood pressure regulation.", "protein": "Aminopeptidase A (APA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "APN is a glycoprotein; glycosylation affects cell surface expression and function.", "mechanism": "Reduced protein expression in ccRCC tumor tissue; involved in angiogenesis and cell adhesion; inhibition suppresses tumor growth.", "protein": "Aminopeptidase N (APN/CD13)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "GGT is a glycoprotein; glycosylation required for enzymatic activity and membrane localization.", "mechanism": "Reduced protein expression in ccRCC tumor tissue; serum GGT associated with poor prognosis due to oxidative stress and metastasis.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker/prognostic marker", "source_pmcid": "PMC12346209" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "NSE is glycosylated; glycosylation may affect stability and detection.", "mechanism": "Upregulated protein expression in ccRCC tumor tissue, especially in older patients; associated with neuroendocrine differentiation.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects APA enzymatic activity and membrane localization.", "mechanism": "APA regulates RAAS by converting angiotensin II to angiotensin III, impacting blood pressure.", "protein": "Aminopeptidase A (APA)", "relationship_type": "causal", "source_pmcid": "PMC12346209" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation required for GGT function.", "mechanism": "Serum GGT levels higher in diabetic patients, possibly due to increased lipid accumulation and inflammation.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Glycosylation affects APN shedding and function.", "mechanism": "APN inhibition decreases angiogenesis and tumor growth; soluble APN elevated in malignant effusions.", "protein": "Aminopeptidase N (APN/CD13)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Renal cell carcinoma (RCC)", "glycan_involvement": "Glycosylation required for GGT enzymatic activity.", "mechanism": "GGT inhibition sensitizes RCC cells to chemotherapy and reduces tumor growth.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346209" }, { "confidence": "medium", "disease": "Renal cell carcinoma (RCC) with intraocular metastasis", "glycan_involvement": "Glycosylation may affect NSE detection.", "mechanism": "Elevated NSE levels associated with intraocular metastasis from RCC.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346209" }, { "confidence": "medium", "disease": "Choriocarcinoma", "glycan_involvement": "APA glycosylation affects cell membrane localization.", "mechanism": "Elevated APA levels found in cytotrophoblast layer of choriocarcinoma cell lines.", "protein": "Aminopeptidase A (APA)", "relationship_type": "biomarker", "source_pmcid": "PMC12346209" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APP trafficking and processing.", "mechanism": "APP is cleaved to generate A\u03b2 peptides, which aggregate and form plaques central to AD pathology.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Extensively glycosylated; glycosylation required for secretion and function.", "mechanism": "CLU sequesters toxic A\u03b2 oligomers into larger, less toxic aggregates and facilitates their clearance.", "protein": "Clusterin (CLU)", "relationship_type": "protective", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for ER localization and chaperone activity.", "mechanism": "Upregulated during ER stress and UPR; modulates APP processing and A\u03b2 production.", "protein": "BiP/GRP78 (HSPA5)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346265" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Facilitates folding and glycosylation of nascent proteins, including APP, reducing misfolded protein accumulation.", "protein": "Calnexin", "relationship_type": "protective", "source_pmcid": "PMC12346265" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for chaperone activity.", "mechanism": "Assists in glycoprotein folding and quality control in the ER, limiting ER stress.", "protein": "Calreticulin", "protein_enriched": { "function": "", "gene_name": "CALR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7P0T861" }, "relationship_type": "protective", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects secretion and substrate specificity.", "mechanism": "Elevated in CSF of AD patients; blocks A\u03b2 fibrillization and is secreted in response to tau pathology.", "protein": "Protein Disulfide Isomerase (PDI)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346265" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for ERAD complex formation.", "mechanism": "Forms ERAD complex with HRD1 to degrade misfolded proteins, maintaining ER homeostasis and neuronal viability.", "protein": "SEL1L", "relationship_type": "protective", "source_pmcid": "PMC12346265" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "ER-resident E3 ligase; degrades abnormal proteins, preventing their accumulation and neurodegeneration.", "protein": "HRD1 (SYVN1)", "protein_enriched": { "function": "E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubM", "gene_name": "SYVN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86TM6" }, "relationship_type": "protective", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status debated; glycan modifications may affect aggregation.", "mechanism": "Aggregates to form plaques, induces ER stress, disrupts calcium homeostasis, and triggers neurodegeneration.", "protein": "Amyloid-\u03b2 (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates aggregation and toxicity.", "mechanism": "Hyperphosphorylated and O-glycosylated tau forms neurofibrillary tangles, blocks ERAD, and sustains UPR.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal", "source_pmcid": "PMC12346265" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CD44 isoforms differ in glycosylation, affecting HA binding and signaling.", "mechanism": "CD44-HA interaction promotes cell migration, proliferation, and tumor progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "HA chain length and abundance modulate extracellular matrix and cell signaling.", "mechanism": "HAS2 overexpression increases HA synthesis, promoting tumor growth and angiogenesis.", "protein": "HAS2", "relationship_type": "causal", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation affects CD44 clustering and HA binding.", "mechanism": "Overexpression of CD44 on immune cells correlates with inflammation and joint damage.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "HA glycan properties directly impact joint lubrication and cartilage health.", "mechanism": "Reduced HA synthesis and MW in synovial fluid leads to decreased viscoelasticity and joint degeneration.", "protein": "HAS1/HAS2/HAS3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346304" }, { "confidence": "medium", "disease": "Lymphatic Disorders", "glycan_involvement": "HA binding to LYVE-1 regulates immune cell trafficking.", "mechanism": "LYVE-1 mediates HA uptake and lymphangiogenesis, relevant in inflammation and tissue repair.", "protein": "LYVE-1", "relationship_type": "biomarker", "source_pmcid": "PMC12346304" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "HA fragmentation alters RHAMM localization and function.", "mechanism": "RHAMM export and interaction with HA fragments promote cell motility and tumor progression.", "protein": "RHAMM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346304" }, { "confidence": "medium", "disease": "Immune Dysregulation", "glycan_involvement": "HA endocytosis and degradation regulate immune homeostasis.", "mechanism": "HARE mediates HA clearance, preventing excessive immune activation.", "protein": "HARE (Stabilin-2)", "protein_enriched": { "function": "", "gene_name": "TMEM40", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8WWA1" }, "relationship_type": "protective", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Inflammatory Skin Diseases (e.g., Rosacea)", "glycan_involvement": "HA size-dependent interaction with TLRs modulates immune response.", "mechanism": "LMW HA binds TLRs, enhancing inflammation; HMW HA downregulates TLR signaling via CD44.", "protein": "TLRs", "relationship_type": "causal", "source_pmcid": "PMC12346304" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Proteoglycan glycosylation stabilizes HA matrix.", "mechanism": "Aggrecan-HA complexes maintain cartilage structure; loss leads to degeneration.", "protein": "Aggrecan", "protein_enriched": { "function": "This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via ", "gene_name": "ACAN", "glycan_count": 47, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G43417UB", "G02815KT", "G02886BB", "G10486CT", "G28541PG", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G84862VB", "G92050GC", "G95865ZB", "G53434XO", "G29068FM", "G88713AC", "G58001LT", "G57317CE", "G04657PL", "G05049YU", "G07246CJ", "G11115RO", "G11314AS", "G14972EH", "G20706XG", "G27058EU", "G27915IV", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G57776ZS", "G68490OW", "G70441OD", "G79666IR", "G80075MS", "G83646BJ", "G87123QX", "G90659AW", "G06247RL", "G47518TP", "G66088HZ", "G83460ZZ", "G84452RH", "G73004SD" ], "uniprot_id": "P16112" }, "relationship_type": "protective", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Wound Healing Disorders (e.g., Diabetic Ulcers)", "glycan_involvement": "HA glycan promotes cell migration and repair.", "mechanism": "HAS2-driven HA synthesis supports tissue regeneration and angiogenesis.", "protein": "HAS2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346304" }, { "confidence": "high", "disease": "Central obesity", "glycan_involvement": "\u03b2-glucans interact with proteins, affecting digestion and absorption.", "mechanism": "\u03b2-glucans from Pleurotus eryngii form complexes with dietary proteins, reducing postprandial release of aromatic amino acids linked to obesity risk.", "protein": "\u03b2-glucan-protein complexes", "relationship_type": "protective", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Transporters are glycoproteins; glycosylation may affect substrate specificity.", "mechanism": "Elevated plasma aromatic amino acids (phenylalanine, tyrosine, tryptophan) are associated with metabolic syndrome.", "protein": "Aromatic amino acid transporters", "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Type 2 diabetes (T2D)", "glycan_involvement": "Transporters are glycoproteins; glycosylation may modulate activity.", "mechanism": "Increased BCAAs in plasma are linked to T2D risk and insulin resistance.", "protein": "Branched-chain amino acid transporters", "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Central obesity", "glycan_involvement": "O-glycosylation affects ghrelin stability and secretion.", "mechanism": "P. eryngii \u03b2-glucans regulate postprandial ghrelin, influencing appetite in obesity.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation is essential for receptor function.", "mechanism": "Altered amino acid profiles and \u03b2-glucan intake may modulate insulin receptor signaling.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL is N-glycosylated; glycosylation affects clearance.", "mechanism": "P. eryngii \u03b2-glucans decrease LDL levels in obese subjects.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Inflammation-mediated diseases", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and activity.", "mechanism": "P. eryngii \u03b2-glucans reduce IL-6, indicating anti-inflammatory effects.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycation/oxidation of LDL promotes atherogenesis.", "mechanism": "P. eryngii \u03b2-glucans lower ox-LDL, reducing cardiovascular risk.", "protein": "Oxidized LDL (ox-LDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "ALT is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "P. eryngii \u03b2-glucans decrease ALT, suggesting improved liver function.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "AST is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "P. eryngii \u03b2-glucans decrease AST, indicating hepatic benefit.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346340" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Not specified", "mechanism": "Overexpression and SNPs associated with aggressiveness; may promote cell growth via peptide processing.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346392" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Not specified", "mechanism": "Overexpression correlates with tumor progression, metastasis, and poor prognosis; activates PI3K/AKT pathway, induces EMT.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346392" }, { "confidence": "high", "disease": "Breast cancer (including TNBC)", "glycan_involvement": "Unique O-glycosylation pattern in MCF-7 cells; may affect secretion/function.", "mechanism": "Elevated in TNBC, correlates with stemness (ALDH1A1), poor prognosis, and drug resistance; promotes proliferation/migration.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346392" }, { "confidence": "high", "disease": "Lung cancer (NSCLC)", "glycan_involvement": "Not specified", "mechanism": "Overexpression correlates with poor prognosis, promotes growth/metastasis via AKT-cMYC pathway; serum CPA4 aids diagnosis.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Head and neck squamous cell carcinoma (SCCHN)", "glycan_involvement": "Not specified", "mechanism": "High expression linked to poor survival; loss of imprinting may drive tumorigenesis.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma (ESCC)", "glycan_involvement": "Not specified", "mechanism": "High expression associated with grade, metastasis, and poor prognosis; co-expressed with ALDH1A1.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Not specified", "mechanism": "Overexpression correlates with proliferation, invasion, metastasis, and poor prognosis; knockdown inhibits tumorigenic traits.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified", "mechanism": "High expression correlates with invasion, metastasis, and poor survival; serum CPA4 predicts prognosis.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "Not specified", "mechanism": "Elevated CPA4 correlates with grade, stage, and stem cell markers (CD90, CD133, ALDH1, CD44); promotes tumor growth.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12346392" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Not specified", "mechanism": "Overexpression linked to advanced stage, poor survival, and altered immune infiltration.", "protein": "Carboxypeptidase A4 (CPA4)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346392" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "O-glycosylation of MUC2 in the Golgi is essential for mucus barrier integrity.", "mechanism": "Structural weakening or breach of the mucus layer due to defective MUC2 glycosylation initiates colitis.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC12346421" }, { "confidence": "high", "disease": "Goblet cell depletion", "glycan_involvement": "Proper O-glycosylation is required for MUC2 secretion and function.", "mechanism": "Loss of glycosylated MUC2 from sentinel goblet cells at crypt openings leads to barrier loss.", "protein": "Mucin 2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "O-glycosylation patterns change in disease.", "mechanism": "Altered expression or glycosylation of MUC5AC is associated with mucosal inflammation.", "protein": "Mucin 5AC (MUC5AC)", "protein_enriched": { "function": "Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a p", "gene_name": "STAB2", "glycan_count": 6, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G49108TO", "G01650EU", "G27058EU", "G28541PG", "G45504EY", "G63041LO" ], "uniprot_id": "Q8WWQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "O-glycosylation affects MUC1 localization and immune interactions.", "mechanism": "MUC1-positive multilamellar organelles are increased during mucosal remodeling and inflammation.", "protein": "Mucin 1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "ManII is required for proper N-glycan processing on glycoproteins including mucins.", "mechanism": "Altered localization or function of ManII disrupts mucin glycosylation, compromising mucus barrier.", "protein": "Mannosidase II (ManII)", "protein_enriched": { "function": "Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide rep", "gene_name": "NDST2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P52849" }, "relationship_type": "causal", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Adds sialic acid to mucin O-glycans, affecting mucus charge and hydration.", "mechanism": "Defective sialylation of mucins increases their precipitation and alters mucus properties.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Transfers galactose to mucin O-glycans, essential for mature glycan structure.", "mechanism": "Impaired galactosylation of mucins affects mucus structure and function.", "protein": "GalT", "relationship_type": "causal", "source_pmcid": "PMC12346421" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "O-glycosylation is critical for MUC2 gel formation and barrier function.", "mechanism": "Properly glycosylated MUC2 forms a protective mucus barrier preventing inflammation.", "protein": "Mucin 2 (MUC2)", "relationship_type": "protective", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Goblet cell depletion", "glycan_involvement": "O-glycosylation modulates MUC1 trafficking and immune signaling.", "mechanism": "Increased MUC1-positive multilamellar organelles indicate altered goblet cell turnover.", "protein": "Mucin 1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Therapies could target O-glycosylation pathways in goblet cells.", "mechanism": "Restoring MUC2 glycosylation or secretion may repair the mucus barrier.", "protein": "Mucin 2 (MUC2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346421" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Acts on glycosidic bonds of phenolic glucosides.", "mechanism": "Hydrolyzes phenolic glucosides to aglycones, increasing phenolic antioxidants in olive oil, which are protective against cardiovascular diseases.", "protein": "\u03b2-glucosidase", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Hydrolyzes ester bonds of glycosylated phenolics.", "mechanism": "Contributes to the formation of phenolic aglycones, enhancing antioxidant content in olive oil, which is linked to cardiovascular protection.", "protein": "Esterase", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Acts on phenolic substrates, some of which are glycosylated.", "mechanism": "Degrades phenolic antioxidants via enzymatic oxidation, reducing olive oil's protective effect against cancer.", "protein": "Polyphenol oxidase (PPO)", "relationship_type": "causal (negative impact)", "source_pmcid": "PMC12346424" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "Acts on phenolic substrates, including glycosylated forms.", "mechanism": "Degrades phenolic antioxidants, potentially reducing neuroprotective effects of olive oil.", "protein": "Peroxidase (POD)", "relationship_type": "causal (negative impact)", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Enzyme is a glycoprotein; activity modulates bioactive lipid and glycan derivatives.", "mechanism": "Generates volatile compounds with health-promoting properties, contributing to olive oil's protective effects.", "protein": "Lipoxygenase", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Cardiovascular diseases", "glycan_involvement": "Act on glycan-rich cell wall components.", "mechanism": "Degrade cell wall polysaccharides, enhancing release of phenolics with cardiovascular benefits.", "protein": "Pectolytic enzymes", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Act on glycan-rich hemicellulose.", "mechanism": "Facilitate release of phenolic antioxidants by degrading hemicellulose, supporting anti-cancer properties.", "protein": "Hemicellulolytic enzymes", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Enzyme may be glycosylated; acts on lipid substrates.", "mechanism": "Releases fatty acids and bioactive lipids, contributing to olive oil's metabolic benefits.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Enzyme may be glycosylated; acts on phospholipids.", "mechanism": "Releases phospholipid-derived antioxidants, potentially protective in neurodegeneration.", "protein": "Phospholipase", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Acts on glycosylated lipids.", "mechanism": "Releases galactolipid-derived bioactives, contributing to anti-cancer effects.", "protein": "Galactolipase", "relationship_type": "protective", "source_pmcid": "PMC12346424" }, { "confidence": "high", "disease": "Leishmaniasis", "glycan_involvement": "YY1 is glycosylated; glycosylation may affect its localization and function.", "mechanism": "YY1 promotes Leishmania survival in macrophages by translocating to cytoplasm and modulating immune signaling.", "protein": "Yin Yang 1 (YY1)", "protein_enriched": { "function": "Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site (PubMed:1532", "gene_name": "YY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P25490" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "Akt is glycosylated; glycosylation may regulate its activity.", "mechanism": "YY1 activates Akt, which suppresses apoptosis and immune responses, favoring Leishmania persistence.", "protein": "Akt (Protein Kinase B)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "STAT1 is glycosylated; glycosylation may modulate signaling.", "mechanism": "Cytoplasmic YY1 interacts with STAT1, reducing STAT1-activated genes and immune defense.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "GSK-3\u03b2 is glycosylated; glycosylation may affect kinase activity.", "mechanism": "Akt activation by YY1 inactivates GSK-3\u03b2, leading to increased IL-10 and immune suppression.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "IL-10 is a glycoprotein; glycosylation is essential for secretion and stability.", "mechanism": "YY1/Akt axis increases IL-10 production, creating an immune-suppressive environment for Leishmania.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "METTL3 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "METTL3-mediated m6A methylation stabilizes YY1 mRNA, promoting cell growth.", "protein": "METTL3", "protein_enriched": { "function": "The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, di", "gene_name": "METTL3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86U44" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Gastric Cancer", "glycan_involvement": "ALKBH5 is glycosylated; glycosylation may regulate demethylase function.", "mechanism": "ALKBH5 removes m6A from YY1 mRNA, decreasing YY1 stability and affecting cancer cell growth.", "protein": "ALKBH5", "protein_enriched": { "function": "Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubM", "gene_name": "ALKBH5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6P6C2" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Leishmaniasis", "glycan_involvement": "Crm1 is glycosylated; glycosylation may regulate nuclear export.", "mechanism": "Crm1 mediates nuclear export of YY1, enabling its cytoplasmic function in Leishmania-infected macrophages.", "protein": "Crm1 (Exportin 1)", "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "medium", "disease": "Vaccinia Virus Infection", "glycan_involvement": "YY1 glycosylation may affect its subcellular localization.", "mechanism": "Vaccinia virus triggers YY1 nuclear export, contributing to viral pathogenesis.", "protein": "Yin Yang 1 (YY1)", "protein_enriched": { "function": "Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site (PubMed:1532", "gene_name": "YY1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P25490" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "low", "disease": "Leishmaniasis", "glycan_involvement": "c-Myc is glycosylated; glycosylation may influence transcriptional activity.", "mechanism": "Leishmania targets c-Myc to promote survival in macrophages.", "protein": "c-Myc", "protein_enriched": { "function": "Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of grow", "gene_name": "MYC", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P01106" }, "relationship_type": "causal", "source_pmcid": "PMC12346476" }, { "confidence": "high", "disease": "Myelosuppression", "glycan_involvement": "N-glycosylation required for stability and activity.", "mechanism": "Stimulates erythropoiesis to counteract chemotherapy-induced myelosuppression.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Aplastic anemia", "glycan_involvement": "N-glycosylation affects receptor binding and bioactivity.", "mechanism": "Upregulated during hematopoietic recovery; regulates platelet production.", "protein": "Thrombopoietin (TPO)", "protein_enriched": { "function": "Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major ", "gene_name": "THPO", "glycan_count": 32, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00227RN", "G00800WJ", "G01817YC", "G14389GM", "G16265MV", "G17689DH", "G44444MB", "G47058MH", "G56501FP", "G57789QC", "G90352XZ", "G94531EZ", "G00031MO", "G01614ZM", "G11629QQ", "G15169WU", "G19075PM", "G22310AV", "G29931IJ", "G39595FH", "G57321FI", "G57581QG", "G64394MX", "G65562ZE", "G69834CE", "G72667IM", "G74722FL", "G81006GJ", "G81263BG", "G84452RH", "G87015RU", "G96170OK" ], "uniprot_id": "P40225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Aplastic anemia", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "Receptor for TPO; activation promotes hematopoietic stem cell renewal.", "protein": "c-MPL (Thrombopoietin receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "high", "disease": "Leukopenia", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Stimulates granulocyte production; used clinically to treat leukopenia.", "protein": "Granulocyte Colony-Stimulating Factor (G-CSF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Myelosuppression", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Decreased expression correlates with reduced inflammation and bone marrow recovery.", "protein": "Tumor Necrosis Factor alpha (TNF\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346513" }, { "confidence": "high", "disease": "Chemotherapy-induced anemia", "glycan_involvement": "N-glycosylation essential for in vivo activity.", "mechanism": "Used to stimulate red blood cell production in anemia secondary to chemotherapy.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation influences receptor binding.", "mechanism": "Promotes platelet production to counteract chemotherapy-induced thrombocytopenia.", "protein": "Thrombopoietin (TPO)", "protein_enriched": { "function": "Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major ", "gene_name": "THPO", "glycan_count": 32, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00227RN", "G00800WJ", "G01817YC", "G14389GM", "G16265MV", "G17689DH", "G44444MB", "G47058MH", "G56501FP", "G57789QC", "G90352XZ", "G94531EZ", "G00031MO", "G01614ZM", "G11629QQ", "G15169WU", "G19075PM", "G22310AV", "G29931IJ", "G39595FH", "G57321FI", "G57581QG", "G64394MX", "G65562ZE", "G69834CE", "G72667IM", "G74722FL", "G81006GJ", "G81263BG", "G84452RH", "G87015RU", "G96170OK" ], "uniprot_id": "P40225" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Myelosuppression", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "Expression reflects granulocyte recovery after cytotoxic insult.", "protein": "Granulocyte Colony-Stimulating Factor (G-CSF)", "relationship_type": "biomarker", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Aplastic anemia", "glycan_involvement": "Glycosylation affects cytokine activity.", "mechanism": "High TNF\u03b1 can suppress hematopoiesis; reduction aids recovery.", "protein": "Tumor Necrosis Factor alpha (TNF\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12346513" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation modulates receptor-ligand interaction.", "mechanism": "Activation by TPO stimulates platelet production.", "protein": "c-MPL (Thrombopoietin receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346513" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "FAP is a glycoprotein; glycosylation may affect its stability and cell surface localization.", "mechanism": "FAP is highly overexpressed in cancer-associated fibroblasts within the tumor microenvironment, enabling targeted PET imaging and radioligand therapy.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "SCLC", "glycan_involvement": "Glycosylation supports FAP's membrane localization and function.", "mechanism": "FAP-targeted radiopharmaceuticals enable imaging and potential therapy in SCLC due to FAP overexpression in tumor stroma.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Lung Adenocarcinoma", "glycan_involvement": "Glycosylation may influence FAP's recognition by radioligands.", "mechanism": "FAP PET/CT shows high sensitivity and specificity for detecting primary and metastatic lung adenocarcinoma.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Squamous Cell Carcinoma (SqCC)", "glycan_involvement": "Glycosylation may modulate FAP's cell surface presentation.", "mechanism": "FAP PET/CT is effective for staging and detection of SqCC due to FAP expression in tumor-associated fibroblasts.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 is glycosylated, which affects its stability and immune recognition.", "mechanism": "PD-L1 expression predicts response to immune checkpoint inhibitors; PET/CT-based radiomics can noninvasively estimate PD-L1 status.", "protein": "Programmed Death-Ligand 1 (PD-L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "EGFR glycosylation modulates receptor function and ligand binding.", "mechanism": "EGFR mutations are detected by PET/CT radiogenomics, guiding targeted therapy.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Metastatic Lung Cancer", "glycan_involvement": "Glycosylation may affect FAP's interaction with imaging agents.", "mechanism": "FAP PET/CT detects nodal and distant metastases with higher sensitivity than FDG PET/CT.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Lung Cancer (general)", "glycan_involvement": "Glycosylation supports FAP's function and targeting.", "mechanism": "FAP-targeted radioligand therapy (RLT) is a promising approach for personalized treatment.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Lung Adenocarcinoma", "glycan_involvement": "PD-L1 glycosylation affects antibody binding and immune evasion.", "mechanism": "High PD-L1 expression correlates with better response to immunotherapy; PET/CT radiomics can predict expression.", "protein": "Programmed Death-Ligand 1 (PD-L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Lung Cancer (general)", "glycan_involvement": "Glycosylation may influence FAP's imaging properties.", "mechanism": "FAP PET/CT provides higher tumor-to-background ratio for detection and staging compared to FDG PET/CT.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346515" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation critical for ECM interactions and integrin binding.", "mechanism": "Promotes tumor invasion, EMT, and stromal remodeling; elevated in malignant EC.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation modulates cell adhesion and endothelial function.", "mechanism": "Reflects angiogenesis and microvessel density; higher levels linked to aggressiveness and poor prognosis.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation affects immunomodulatory activity.", "mechanism": "Associated with EC progression and patient survival.", "protein": "Glycodelin (PAEP)", "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation influences reproductive tract function.", "mechanism": "Linked to EC progression and survival.", "protein": "OVGP1", "protein_enriched": { "function": "Binds to oocyte zona pellucida in vivo. May play a role in the fertilization process and/or early embryonic development", "gene_name": "OVGP1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q12889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation modulates cell adhesion and migration.", "mechanism": "High expression correlates with aggressiveness, invasion, and poor survival.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Serum levels correlate with advanced stage and invasion.", "protein": "WFDC2 (HE4)", "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Endometrial cancer", "glycan_involvement": "Extensive O-glycosylation modulates immune evasion and cell adhesion.", "mechanism": "Serum levels associated with advanced stage and lymph node involvement.", "protein": "CA-125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "medium", "disease": "Benign endometrial lesions", "glycan_involvement": "Glycosylation affects ECM structure.", "mechanism": "Lower serum levels compared to malignant EC.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "Glycosylation modulates cell-cell adhesion.", "mechanism": "Reduced expression linked to invasion and metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Serous-type endometrial cancer", "glycan_involvement": "N-glycosylation affects receptor dimerization and signaling.", "mechanism": "Overexpression linked to poor survival; targetable by trastuzumab.", "protein": "ERBB2 (HER2/neu)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346555" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Arg47His alters glycosylation status, affecting ligand binding and receptor function.", "mechanism": "Mutations (e.g., Arg47His, Arg62His) impair microglial phagocytosis and amyloid clearance, increase neuroinflammation.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Frontotemporal dementia", "glycan_involvement": "Mutations affect folding and trafficking, possibly altering glycosylation.", "mechanism": "Mutations (e.g., His157Tyr, Tyr38Cys) disturb microglial function and TDP-43 clearance, leading to neurodegeneration.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Nasu-Hakola disease", "glycan_involvement": "Mutations disrupt folding and ER trafficking, impacting glycosylation and cell surface expression.", "mechanism": "Homozygous loss-of-function mutations (e.g., Tyr38Cys, Thr66Met, Gln33Ter) cause microglial and osteoclast dysfunction, leading to dementia and bone cysts.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12346578" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Altered glycosylation may affect ligand binding and microglial activation.", "mechanism": "Mutations (e.g., Arg47His) and deficiency increase neuroinflammation and \u03b1-synuclein accumulation, accelerating dopaminergic neuron loss.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "risk factor", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Proteolytic cleavage at His157 (stalk region) releases sTREM2; glycosylation may affect shedding.", "mechanism": "CSF soluble TREM2 (sTREM2) levels correlate with microglial activation and disease progression.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Therapeutic antibodies target extracellular glycosylated domains.", "mechanism": "Monoclonal antibodies (e.g., AL002, CGX101) activate TREM2 signaling to enhance microglial phagocytosis and reduce neuroinflammation.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of TREM2 extracellular domain affects APOE binding.", "mechanism": "Interaction with APOE4 modulates amyloid clearance and neuroinflammation; TREM2-APOE binding is glycan-dependent.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "modifier", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Nasu-Hakola disease", "glycan_involvement": "Mutations affect glycosylation and complex formation.", "mechanism": "TREM2-DAP12 complex deficiency impairs osteoclast differentiation and bone resorption.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12346578" }, { "confidence": "medium", "disease": "Frontotemporal dementia", "glycan_involvement": "Proper glycosylation required for receptor trafficking and function.", "mechanism": "Restoring TREM2 function may enhance microglial clearance of TDP-43 aggregates.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346578" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Mutation at cleavage site may alter glycosylation and proteolytic processing.", "mechanism": "His157Tyr mutation increases sTREM2 shedding, with variable effects on amyloid pathology and synaptic plasticity.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "modifier", "source_pmcid": "PMC12346578" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Aberrant glycosylation at Ser195 targets PD-L1 for ERAD and degradation.", "mechanism": "Metformin promotes proteasomal degradation of aberrantly glycosylated PD-L1, reducing immune suppression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Metformin inhibits VEGF expression via AMPK activation, suppressing angiogenesis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Senescence-associated inflammation", "glycan_involvement": "MMP-3 glycosylation modulates secretion and activity.", "mechanism": "Metformin reduces MMP-3 (SASP factor) secretion, mitigating pro-inflammatory aging environment.", "protein": "MMP-3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346583" }, { "confidence": "high", "disease": "Senescence-associated inflammation", "glycan_involvement": "IL-6 glycosylation affects receptor binding and stability.", "mechanism": "Metformin suppresses IL-6 release, reducing inflammaging and SASP.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "CD133 is heavily glycosylated; glycosylation is essential for its cell surface localization.", "mechanism": "Metformin reduces CD133+ cancer stem cell populations, lowering tumor-initiating potential.", "protein": "CD133", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "DR4 glycosylation modulates ligand binding and apoptotic signaling.", "mechanism": "Metformin upregulates DR4, sensitizing cancer cells to apoptosis.", "protein": "DR4", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "DR5 glycosylation affects receptor function and apoptotic signaling.", "mechanism": "Metformin upregulates DR5, enhancing apoptotic response in tumor cells.", "protein": "DR5", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Immune exhaustion in tumors", "glycan_involvement": "FOXP3 function can be modulated by glycoprotein interactions.", "mechanism": "Metformin downregulates FOXP3 in Tregs, reducing immunosuppression in tumor microenvironment.", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "LAMP-1 is highly glycosylated; glycosylation is critical for lysosomal targeting and function.", "mechanism": "Metformin increases CD107a expression in NK cells, reflecting enhanced cytotoxicity.", "protein": "CD107a (LAMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12346583" }, { "confidence": "medium", "disease": "Obesity-related inflammation", "glycan_involvement": "Outer membrane glycoproteins interact with host mucins and immune system.", "mechanism": "Metformin increases Akkermansia abundance, improving gut barrier and reducing inflammation.", "protein": "Akkermansia muciniphila outer membrane proteins", "relationship_type": "protective", "source_pmcid": "PMC12346583" }, { "confidence": "high", "disease": "Non-Alcoholic Steatohepatitis (NASH)", "glycan_involvement": "Enhanced O-GlcNAcylation of proteins", "mechanism": "Upregulation of GFPT1 increases UDP-GlcNAc and O-GlcNAcylation, promoting insulin resistance and inflammation in NASH.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "O-GlcNAc modification of signaling proteins", "mechanism": "GFPT1-driven O-GlcNAcylation impairs insulin signaling.", "protein": "GFPT1", "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects ANGPTL4 secretion and function", "mechanism": "Downregulation of ANGPTL4 disrupts lipid metabolism via LPL inhibition, contributing to dyslipidemia.", "protein": "ANGPTL4", "protein_enriched": { "function": "Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697", "gene_name": "ANGPTL4", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G14994KB", "G22310AV", "G23863VK", "G27058EU", "G31852PQ", "G37412TK", "G37881RL", "G41071NU", "G45395BF", "G45495MK", "G48414YA", "G52527GH", "G56784JY", "G57818FI", "G62461SM", "G62765YT", "G71146HJ", "G75983OB", "G80920RR", "G84452RH", "G90659AW", "G43417UB", "G53434XO", "G88713AC" ], "uniprot_id": "Q9BY76" }, "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation required for ABCA1 stability and trafficking", "mechanism": "Upregulation of ABCA1 promotes cholesterol efflux, reducing atherosclerosis risk.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates ABCG1 function", "mechanism": "ABCG1 upregulation enhances cholesterol efflux from cells.", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "protective", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences CAV1 membrane localization", "mechanism": "Cholesterol-induced downregulation of CAV1 disrupts lipid raft organization, affecting vascular signaling.", "protein": "CAV1", "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "NASH-associated liver cancer", "glycan_involvement": "N-glycosylation modulates THBS1 secretion", "mechanism": "THBS1 upregulation correlates with vascular remodeling in NASH-related cancer.", "protein": "THBS1", "relationship_type": "biomarker", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for NT5E enzymatic activity", "mechanism": "NT5E upregulation links purinergic signaling to lipid metabolism and inflammation.", "protein": "NT5E", "protein_enriched": { "function": "Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate (PubMed:21933152, PubMed:22997138, PubMed:", "gene_name": "NT5E", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G08290VR", "G17208MA", "G43223CG", "G62765YT", "G70441OD", "G84862VB", "G90659AW", "G00912UN", "G04657PL", "G07246CJ", "G08918WF", "G14972EH", "G27058EU", "G35541EV", "G41071NU", "G45395BF", "G57776ZS", "G65184UU", "G70232NH", "G79666IR", "G83646BJ", "G86880BF", "G87661QW", "G80075MS", "G49108TO" ], "uniprot_id": "P21589" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346660" }, { "confidence": "medium", "disease": "NAFLD (Non-Alcoholic Fatty Liver Disease)", "glycan_involvement": "Glycosylation affects SOAT1 function", "mechanism": "SOAT1 upregulation alters cholesterol esterification, contributing to hepatic lipid accumulation.", "protein": "SOAT1", "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "low", "disease": "Oxidative stress-related disorders", "glycan_involvement": "Glycosylation modulates PLD1 activity", "mechanism": "PLD1 upregulation drives phospholipid remodeling and oxidative stress under cholesterol overload.", "protein": "PLD1", "relationship_type": "causal", "source_pmcid": "PMC12346660" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Not specified", "mechanism": "Promotes immune evasion, metastasis via MMP2/STAT3; high expression linked to poor prognosis and resistance to PD-1/PD-L1 therapy.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Not specified", "mechanism": "Overexpression drives proliferation, EMT, immune suppression; targeted by CAR-T and ADC therapies.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "Not specified", "mechanism": "Upregulation promotes proliferation, migration, glucose metabolism; targeting B7-H3 enhances NK cell activity and therapy response.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Aberrant glycosylation stabilizes B7-H3, protects from ubiquitination, enhances immune evasion.", "mechanism": "High expression correlates with poor prognosis, immune evasion, metastasis; soluble B7-H3 proposed as diagnostic biomarker.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Aberrant glycosylation stabilizes B7-H3, increases resistance to therapy.", "mechanism": "Upregulated in tumor-associated macrophages, drives immunosuppressive TME, angiogenesis, resistance to PD-L1 therapy.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Not specified", "mechanism": "High expression associated with poor differentiation, advanced stage, lymph node involvement; facilitates migration/invasion.", "protein": "B7-H3 (CD276)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Small-cell lung cancer (SCLC)", "glycan_involvement": "Not specified", "mechanism": "Overexpressed in majority of SCLC cases; correlates with tumor size and poor survival; under clinical evaluation as target.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "medium", "disease": "Medulloblastoma", "glycan_involvement": "Not specified", "mechanism": "High expression linked to reduced T-cell infiltration, poor survival; promotes exosome secretion and angiogenesis.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "medium", "disease": "Craniopharyngioma", "glycan_involvement": "Not specified", "mechanism": "Highly expressed in all CP samples; high levels correlate with poor survival, low T-cell infiltration, high macrophages.", "protein": "B7-H3 (CD276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346708" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Not specified", "mechanism": "High B7-H3 expression correlates with increased FOXP3+ Tregs and poor prognosis; promotes immunosuppressive TME.", "protein": "B7-H3 (CD276)", "relationship_type": "causal", "source_pmcid": "PMC12346708" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux transporter limits drug accumulation in GBM; decreased in BTB microvessels.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346771" }, { "confidence": "high", "disease": "Brain metastasis (breast, lung, melanoma)", "glycan_involvement": "N-glycosylation affects stability and trafficking.", "mechanism": "Efflux transporter restricts drug entry; undetectable in most metastatic BTB microvessels.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346771" }, { "confidence": "high", "disease": "Blood\u2013brain barrier dysfunction", "glycan_involvement": "Glycosylation modulates tight junction assembly.", "mechanism": "Downregulation increases BBB permeability; knockout leads to brain edema.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Blood\u2013brain barrier dysfunction", "glycan_involvement": "Glycosylation influences junctional stability.", "mechanism": "Loss correlates with BBB breakdown in tumors.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "Regulates leukocyte adhesion and TJ formation; upregulated in inflammation.", "protein": "Junctional Adhesion Molecule-A (JAM-A)", "protein_enriched": { "function": "", "gene_name": "CTAG1A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P78358" }, "relationship_type": "causal", "source_pmcid": "PMC12346771" }, { "confidence": "high", "disease": "Blood\u2013brain barrier dysfunction", "glycan_involvement": "Glycosylation essential for adhesive function.", "mechanism": "Maintains BBB integrity; regulates Claudin-5 transcription.", "protein": "VE-cadherin", "relationship_type": "protective", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation modulates ECM interactions.", "mechanism": "Secreted by pericytes; inhibits transcytosis, stabilizing BBB.", "protein": "Vitronectin", "protein_enriched": { "function": "Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "protective", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Astrocytoma", "glycan_involvement": "Heparan sulfate glycosylation critical for BM structure.", "mechanism": "Loss of agrin-mediated polarization in astrocytic end-feet linked to tumor migration.", "protein": "Agrin", "protein_enriched": { "function": "Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Com", "gene_name": "AGRN", "glycan_count": 122, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G29068FM", "G43417UB", "G29063QY", "G30190ML", "G88713AC", "G27391WQ", "G40740AD", "G58001LT", "G73004SD", "G49108TO", "G00912UN", "G01650EU", "G02815KT", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08293MJ", "G08918WF", "G10486CT", "G27058EU", "G27947YN", "G28541PG", "G37399XV", "G37412TK", "G40574BA", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G46691LC", "G48414YA", "G49906RN", "G58954YZ", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G68490OW", "G70619PT", "G72747WU", "G72790NZ", "G80920RR", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G04657PL", "G07755XJ", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G17208MA", "G20706XG", "G22572EH", "G25079LO", "G28622IK", "G29545VG", "G30769VJ", "G34029GR", "G37995HC", "G39619TI", "G43669FQ", "G45504EY", "G46503DX", "G47950XN", "G48584BU", "G50282JC", "G51653BI", "G55132BD", "G60177UT", "G60834IK", "G66163OV", "G70223PD", "G70441OD", "G73968GN", "G75568BH", "G75983OB", "G76295SF", "G77547TA", "G78790NZ", "G80075MS", "G80479JV", "G82830MN", "G84862VB", "G85269DF", "G88891KO", "G90575OW", "G90734RJ", "G92135MA", "G25451PN", "G70101JE", "G15169WU", "G24528MX", "G27126ED", "G37509XX", "G40206WX", "G49642SA", "G77669RF", "G78787DI", "G83460ZZ", "G87389XI", "G90382BL", "G92551JA", "G57317CE", "G53434XO" ], "uniprot_id": "O00468" }, "relationship_type": "causal", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Brain metastasis (breast, lung, melanoma)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Promotes neuroinflammation and metastatic niche formation via astrocyte activation.", "protein": "Lipocalin-2 (LCN2)", "relationship_type": "causal", "source_pmcid": "PMC12346771" }, { "confidence": "medium", "disease": "Brain metastasis (breast cancer)", "glycan_involvement": "N-glycosylation affects enzymatic activity.", "mechanism": "Secreted by HER2+ breast cancer; increases BBB permeability for metastasis.", "protein": "ENPP1", "protein_enriched": { "function": "Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone min", "gene_name": "ENPP1", "glycan_count": 45, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G80920RR", "G11629QQ", "G20312EM", "G25418HZ", "G25451PN", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G47518TP", "G60177UT", "G68490OW", "G77582RK", "G83229XP", "G83460ZZ", "G84452RH", "G86795LJ", "G87661QW", "G92081HT", "G92135MA", "G95133RI", "G02886BB", "G05724UK", "G07246CJ", "G10773YW", "G20210JR", "G28541PG", "G47644PP", "G49018RC", "G51640FO", "G59924QI", "G63041LO", "G70619PT", "G72747WU", "G83646BJ", "G84820NF", "G90659AW", "G92062TF", "G96091TT", "G46503DX", "G70232NH", "G85282JO", "G27915IV", "G84225JN", "G49108TO" ], "uniprot_id": "P22413" }, "relationship_type": "causal", "source_pmcid": "PMC12346771" }, { "confidence": "high", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "BSEP is a glycoprotein; glycosylation is essential for its membrane localization and function.", "mechanism": "Upregulation of BSEP by AEE promotes bile acid export, reducing hepatic lipid accumulation.", "protein": "Bile Salt Export Pump (BSEP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346774" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "CYP7A1 glycosylation affects enzyme stability and activity.", "mechanism": "AEE upregulates CYP7A1, enhancing conversion of cholesterol to bile acids, reducing steatosis.", "protein": "Cholesterol 7\u03b1-hydroxylase (CYP7A1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346774" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "PPAR\u03b1 glycosylation modulates receptor activity and nuclear localization.", "mechanism": "AEE upregulates PPAR\u03b1, promoting fatty acid oxidation and improving lipid metabolism.", "protein": "Peroxisome Proliferator-Activated Receptor Alpha (PPAR\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346774" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "LRH-1 glycosylation may affect DNA binding and transcriptional activity.", "mechanism": "AEE upregulates LRH-1, activating CYP7A1 transcription and bile acid synthesis.", "protein": "Liver Receptor Homolog-1 (LRH-1)", "protein_enriched": { "function": "Orphan nuclear receptor that binds DNA as a monomer to the 5'-TCAAGGCCA-3' sequence and controls expression of target genes: regulates key biological processes, such as early embryonic development, ch", "gene_name": "NR5A2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00482" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346774" }, { "confidence": "high", "disease": "Glucose Metabolism Disorder", "glycan_involvement": "GSP is formed by non-enzymatic glycation of serum proteins.", "mechanism": "Elevated GSP reflects chronic hyperglycemia in NAFLD and metabolic syndrome.", "protein": "Glycosylated Serum Protein (GSP)", "relationship_type": "biomarker", "source_pmcid": "PMC12346774" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL glycosylation affects receptor binding and clearance.", "mechanism": "Elevated LDL is a hallmark of dyslipidemia and NAFLD; AEE reduces LDL levels.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346774" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Sulfation and glyco-conjugation enhance bile acid solubility and detoxification.", "mechanism": "AEE increases taurocholic acid 3-sulfate, reducing bile acid cytotoxicity and liver injury.", "protein": "Taurocholic Acid 3-sulfate", "relationship_type": "protective", "source_pmcid": "PMC12346774" }, { "confidence": "medium", "disease": "Liver Steatosis", "glycan_involvement": "LysoPC is a glycolipid; glycan moieties influence membrane dynamics.", "mechanism": "LysoPC levels decrease in HFD-induced steatosis; AEE restores levels, indicating improved lipid metabolism.", "protein": "LysoPC (16:0/0:0)", "relationship_type": "biomarker", "source_pmcid": "PMC12346774" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "ALT glycosylation affects enzyme secretion and stability.", "mechanism": "ALT elevation indicates hepatocellular injury in NAFLD; AEE reduces ALT activity.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12346774" }, { "confidence": "medium", "disease": "Liver Injury", "glycan_involvement": "AST glycosylation modulates enzyme activity.", "mechanism": "AST elevation reflects liver damage in NAFLD; AEE reduces AST activity.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346774" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "VEGF-A is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "VEGF-A promotes angiogenesis and endothelial repair; E2 upregulates VEGF-A via miR-193a-3p downregulation.", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346790" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "ALK1 is glycosylated; glycosylation required for cell surface expression and signaling.", "mechanism": "ALK1/SMAD1/5/8 pathway promotes angiogenesis; E2 upregulates ALK1 via miR-193a-3p downregulation.", "protein": "ALK1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates VEGF-A stability and activity.", "mechanism": "E2-induced VEGF-A expression enhances endothelial repair, reducing atherosclerotic risk.", "protein": "VEGF-A", "relationship_type": "protective", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects ALK1 receptor function.", "mechanism": "ALK1-mediated angiogenesis supports vascular integrity, counteracting hypertension.", "protein": "ALK1", "relationship_type": "protective", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation required for VEGF-A secretion.", "mechanism": "VEGF-A-driven endothelial repair reduces thrombosis risk.", "protein": "VEGF-A", "relationship_type": "protective", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Restenosis", "glycan_involvement": "Glycosylation necessary for ALK1 function.", "mechanism": "ALK1 signaling promotes reendothelialization after vascular injury.", "protein": "ALK1", "relationship_type": "protective", "source_pmcid": "PMC12346790" }, { "confidence": "low", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation impacts VEGF-A bioactivity.", "mechanism": "VEGF-A supports microvascular growth, mitigating cardiomyopathy.", "protein": "VEGF-A", "relationship_type": "protective", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation enhances VEGF-A tumor angiogenic potential.", "mechanism": "VEGF-A-driven angiogenesis contributes to tumor growth; E2 may upregulate VEGF-A.", "protein": "VEGF-A", "relationship_type": "causal", "source_pmcid": "PMC12346790" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation required for ALK1 receptor activity.", "mechanism": "ALK1 pathway activation can promote tumor angiogenesis.", "protein": "ALK1", "relationship_type": "causal", "source_pmcid": "PMC12346790" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation affects detection and quantification in assays.", "mechanism": "Circulating VEGF-A levels reflect endothelial health and angiogenic activity.", "protein": "VEGF-A", "relationship_type": "biomarker", "source_pmcid": "PMC12346790" }, { "confidence": "high", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation modulates inhibitory activity and cell interactions.", "mechanism": "Released after SCI, acts as myelin-associated inhibitor (MAI) that impedes remyelination and axonal regrowth.", "protein": "Myelin-associated glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12346836" }, { "confidence": "high", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation affects receptor binding and inhibitory function.", "mechanism": "Acts as a MAI, inhibits anatomical rearrangements and plasticity needed for remyelination.", "protein": "Oligodendrocyte myelin glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12346836" }, { "confidence": "high", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Released by oligodendrocytes post-SCI, inhibits axonal regeneration and remyelination.", "protein": "Nogo-A", "protein_enriched": { "function": "Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:24262037, PubMed:25612671, PubMed:27619977). They regulate membrane morphogenesis in the ER by promotin", "gene_name": "RTN4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q9NQC3" }, "relationship_type": "causal", "source_pmcid": "PMC12346836" }, { "confidence": "high", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Sulfated glycosaminoglycan chains mediate inhibitory effects.", "mechanism": "Upregulated by reactive astrocytes, CSPGs inhibit OPC migration, differentiation, and remyelination.", "protein": "Chondroitin sulfate proteoglycans (CSPGs)", "relationship_type": "causal", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation may influence antigenicity and immune recognition.", "mechanism": "Autoimmune response against MBP contributes to demyelination in MS and SCI.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation modulates receptor interaction and signaling.", "mechanism": "Promotes OPC transformation into myelinating Schwann cells, aiding remyelination and functional recovery.", "protein": "Neuregulin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation affects stability and receptor binding.", "mechanism": "Acts as chemoattractant for OPCs, promoting migration to demyelinated regions.", "protein": "PDGF-AA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Enhances OPC motility and proliferation, supporting remyelination.", "protein": "Fibroblast Growth Factor 2 (FGF2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Astrocyte-derived Endothelin-1 upregulates Jagged1, activating Notch pathway and inhibiting remyelination.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal", "source_pmcid": "PMC12346836" }, { "confidence": "medium", "disease": "Spinal cord injury (SCI)", "glycan_involvement": "Glycosaminoglycan chains essential for CSPG interaction.", "mechanism": "Scavenges CSPGs and suppresses their synthesis, promoting OPC migration and remyelination.", "protein": "Decorin", "relationship_type": "protective", "source_pmcid": "PMC12346836" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "MBP is a structural glycoprotein of myelin; glycosylation status not directly discussed.", "mechanism": "Reduced MBP expression in oligodendrocytes leads to myelin damage and contributes to PD pathogenesis.", "protein": "MBP", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "STAT5B is not a glycoprotein; regulates glycoprotein MBP.", "mechanism": "STAT5B overexpression in oligodendrocytes restores MBP transcription, improves myelin integrity, and protects against dopaminergic neuron loss.", "protein": "STAT5B", "relationship_type": "protective", "source_pmcid": "PMC12346846" }, { "confidence": "high", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "DNMT3A is not a glycoprotein; acts via epigenetic regulation of glycoprotein MBP.", "mechanism": "DNMT3A-mediated hypermethylation of STAT5B promoter represses STAT5B expression, leading to MBP downregulation and myelin injury.", "protein": "DNMT3A", "protein_enriched": { "function": "Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation ", "gene_name": "DNMT3A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K1" }, "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "MAG is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "MAG promoter used for oligodendrocyte-specific expression; MAG downregulated in PD oligodendrocytes, contributing to myelin impairment.", "protein": "MAG", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "PLP1 is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "PLP1 downregulation in PD oligodendrocytes correlates with impaired myelination.", "protein": "PLP1", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "MOG downregulation in PD oligodendrocytes correlates with myelin impairment.", "protein": "MOG", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Mobp is a glycoprotein; glycosylation status not directly discussed.", "mechanism": "Mobp downregulation in PD oligodendrocytes correlates with myelin impairment.", "protein": "Mobp", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Sox10 is a transcription factor; regulates glycoprotein genes.", "mechanism": "Sox10 downregulation in PD oligodendrocytes impairs myelin gene transcription.", "protein": "Sox10", "relationship_type": "causal", "source_pmcid": "PMC12346846" }, { "confidence": "high", "disease": "Dopaminergic Neuron Degeneration", "glycan_involvement": "TH is not a glycoprotein.", "mechanism": "TH expression is reduced in PD, indicating dopaminergic neuron loss.", "protein": "TH", "relationship_type": "biomarker", "source_pmcid": "PMC12346846" }, { "confidence": "medium", "disease": "Motor Dysfunction", "glycan_involvement": "NfL is not a glycoprotein.", "mechanism": "Elevated NfL in PD models reflects neuronal damage and motor impairment.", "protein": "NfL", "protein_enriched": { "function": "Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that", "gene_name": "NEFH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12036" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346846" }, { "confidence": "high", "disease": "Valvular hemangioma", "glycan_involvement": "CD31 is a heavily glycosylated adhesion molecule; glycosylation affects cell-cell interactions.", "mechanism": "CD31-positive endothelial cells line vascular spaces in hemangiomas.", "protein": "CD31", "relationship_type": "biomarker", "source_pmcid": "PMC12346864" }, { "confidence": "high", "disease": "Valvular hemangioma", "glycan_involvement": "CD34 is a sialomucin glycoprotein; glycosylation modulates cell adhesion and migration.", "mechanism": "CD34 marks endothelial cells in hemangiomas, indicating vascular origin.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Proliferative vascular disease", "glycan_involvement": "N-glycosylation of ICAM-1 regulates its adhesive function and immune interactions.", "mechanism": "Upregulated by STAT1/SP1, ICAM-1 promotes vascular inflammation and neovascularization.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Valvular hemangioma", "glycan_involvement": "NOTCH1 glycosylation modulates ligand binding and signaling.", "mechanism": "NOTCH1 signaling regulates EndMT/MEndoT, affecting vascularization and hemangioma formation.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "causal", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Valvular hemangioma", "glycan_involvement": "Glycosylation affects TGF-\u03b21 secretion and receptor interaction.", "mechanism": "TGF-\u03b21 triggers EndMT, leading to mesenchymal transformation and vascular anomaly.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Cardiac valve tumor", "glycan_involvement": "Glycosylation required for WNT1 secretion and activity.", "mechanism": "WNT1 pathway involved in EndMT/MEndoT, contributing to abnormal valve vascularization.", "protein": "WNT1", "relationship_type": "causal", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Vascular malformations", "glycan_involvement": "Glycosylation may affect stability and signaling.", "mechanism": "PIK3CA/AKT pathway drives endothelial proliferation and vascular anomaly.", "protein": "PIK3CA", "relationship_type": "causal", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "Glycosylation modulates ICAM-1's interaction with immune cells.", "mechanism": "ICAM-1 upregulation enhances tumor cell migration and angiogenesis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation influences CD34's adhesive properties.", "mechanism": "CD34-positive cells contribute to neovascularization in atherosclerotic plaques.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346864" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation affects ICAM-1's immune recognition.", "mechanism": "Elevated ICAM-1 indicates vascular inflammation post-infarction.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12346864" }, { "confidence": "high", "disease": "NPC metastasis", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Promotes EMT and metastasis via NF-\u03baB pathway; inhibition sensitises cells to cisplatin.", "protein": "SQSTM1/p62", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma (NPC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "High expression correlates with poor survival and chemoradiotherapy resistance, especially under hypoxia.", "protein": "Beclin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "Nasopharyngeal carcinoma (NPC)", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Overexpression correlates with poor prognosis and regulates autophagy via mTOR/p53 pathways.", "protein": "Aurora kinase A (AURKA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "high", "disease": "NPC chemoresistance", "glycan_involvement": "N-glycosylation at Asn176 is essential for FOXD1 function.", "mechanism": "Promotes gemcitabine resistance by activating BNIP3; stability and nuclear localisation enhanced by N-glycosylation at Asn176 via ALG3.", "protein": "FOXD1", "protein_enriched": { "function": "Transcriptional activator required for the development of normal hearing, sense of balance and kidney function. Required for the expression of SLC26A4/PDS, JAG1 and COCH in a subset of epithelial cell", "gene_name": "FOXI1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12951" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "NPC radioresistance", "glycan_involvement": "EGFR is a heavily glycosylated receptor; glycosylation affects stability and signalling.", "mechanism": "EGFR interacts with LAPTM4B and Beclin-1 to promote autophagy and radioresistance.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "NPC radioresistance", "glycan_involvement": "LAPTM4B is a glycoprotein; glycosylation may affect lysosomal localisation.", "mechanism": "Interacts with Beclin-1 to trigger autophagosome formation and confer radioresistance.", "protein": "LAPTM4B", "protein_enriched": { "function": "Required for optimal lysosomal function (PubMed:21224396). Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regula", "gene_name": "LAPTM4B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q86VI4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "high", "disease": "NPC immune evasion", "glycan_involvement": "Galectin-9 binds beta-galactoside glycans on cell surfaces.", "mechanism": "Induces autophagy in tumour cells upon CTL contact, suppressing necrosis and impairing CTL-mediated killing.", "protein": "Galectin-9 (G9)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "NPC radioresistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Promotes radioresistance by inhibiting PI3K/mTOR and enhancing autophagy.", "protein": "Annexin A6 (ANXA6)", "relationship_type": "causal", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "NPC radioresistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Upregulated by EBV LMP1; disrupts Bcl-2-Beclin-1 complex to promote autophagy and radioresistance.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "high", "disease": "NPC chemoresistance", "glycan_involvement": "ALG3 catalyses N-glycosylation of FOXD1 at Asn176.", "mechanism": "Mediates N-glycosylation of FOXD1, enhancing its stability and nuclear localisation, promoting chemoresistance.", "protein": "ALG3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12346892" }, { "confidence": "medium", "disease": "Extended-spectrum \u03b2-lactamase (ESBL)-producing E. coli infection", "glycan_involvement": "Likely N-glycosylation modulates membrane localization and stability.", "mechanism": "Downregulation of BamC reduces outer membrane permeability, contributing to \u03b2-lactam resistance.", "protein": "BamC", "protein_enriched": { "function": "Part of the outer membrane protein assembly complex (Bam), which is involved in assembly and insertion of beta-barrel proteins into the outer membrane. Constitutes, with BamD, the core component of th", "gene_name": "bamA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0A940" }, "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "medium", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Glycosylation may affect folding and membrane insertion.", "mechanism": "Alternative uptake route for antibiotics via BamA complements porin-mediated transport.", "protein": "BamA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q50997" }, "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Edwardsiella tarda infection", "glycan_involvement": "Glycosylation may regulate channel function.", "mechanism": "Upregulation of OmpA increases kanamycin influx, sensitizing bacteria to aminoglycosides.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Edwardsiella tarda infection", "glycan_involvement": "Glycosylation may affect transporter activity.", "mechanism": "NagE upregulation enhances antibiotic influx; deletion reduces intracellular kanamycin.", "protein": "NagE", "protein_enriched": { "function": "Part of the ABC transporter complex MglABC involved in galactose/methyl galactoside import (Probable). In addition, binds D-galactose and D-glucose and plays a role in the chemotaxis towards these two", "gene_name": "mglB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0AEE5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Edwardsiella tarda infection", "glycan_involvement": "Glycosylation may modulate substrate specificity.", "mechanism": "FadL upregulation increases kanamycin influx; deletion lowers drug accumulation.", "protein": "FadL", "protein_enriched": { "function": "Catalyzes the deamidation of nicotinamide (NAM) into nicotinate (PubMed:4399474, PubMed:8726014). Likely functions in the cyclical salvage pathway for production of NAD from nicotinamide (PubMed:43994", "gene_name": "pncA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P21369" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12346982" }, { "confidence": "medium", "disease": "Multi-drug resistant Acinetobacter baumannii infection", "glycan_involvement": "Direct glycosylation of ATP alters metabolic regulation.", "mechanism": "Glycosylation of ATP is a unique signature of MDR A. baumannii, possibly regulating metabolic or transport pathways.", "protein": "ATP (glycosylated)", "relationship_type": "biomarker", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Methicillin-resistant Staphylococcus aureus (MRSA) infection", "glycan_involvement": "Glycosylation may affect protein folding and antibiotic binding.", "mechanism": "PBP2a induction confers resistance to \u03b2-lactams by target bypass.", "protein": "PBP2a", "protein_enriched": { "function": "Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 and acts as a key regulator of meiosis during both prophase I and metaphase II (PubMed:29606300). Required to maintai", "gene_name": "WEE2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P0C1S8" }, "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "medium", "disease": "Extended-spectrum \u03b2-lactamase (ESBL)-producing E. coli infection", "glycan_involvement": "Glycosylation influences channel function.", "mechanism": "Upregulation of OmpC may facilitate antibiotic transport into outer membrane vesicles for \u03b2-lactamase hydrolysis.", "protein": "OmpC", "protein_enriched": { "function": "Forms pores that allow passive diffusion of small molecules across the outer membrane", "gene_name": "ompC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06996" }, "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "medium", "disease": "Extended-spectrum \u03b2-lactamase (ESBL)-producing E. coli infection", "glycan_involvement": "Glycosylation modulates membrane localization.", "mechanism": "Upregulation under antibiotic stress may aid in drug transport and resistance.", "protein": "OmpW", "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Multi-drug resistant Enterobacterales infection", "glycan_involvement": "Glycosylation may regulate efflux activity.", "mechanism": "Upregulation of TolC efflux pump expels antibiotics, contributing to multidrug resistance.", "protein": "TolC", "protein_enriched": { "function": "Outer membrane channel, which is required for the function of several efflux systems such as AcrAB-TolC, AcrEF-TolC, EmrAB-TolC and MacAB-TolC. These systems are involved in export of antibiotics and ", "gene_name": "tolC", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02930" }, "relationship_type": "causal", "source_pmcid": "PMC12346982" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation stabilizes HLA structure, affecting antigen presentation and immunogenicity.", "mechanism": "Predicts increased risk of anti-drug antibody (ADA) formation and secondary loss of response to anti-TNF therapy.", "protein": "HLA-DQA1*05", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation modulates peptide binding and immune recognition.", "mechanism": "Associated with increased immunogenicity and ADA formation during anti-TNF therapy (especially infliximab).", "protein": "HLA-DQA1*05", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation affects HLA surface expression and immune interactions.", "mechanism": "Linked to higher risk of ADA formation and reduced efficacy of anti-TNF agents.", "protein": "HLA-DQA1*05", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation influences antigen presentation and immune activation.", "mechanism": "Associated with increased disease severity, risk of hospitalization, and extraintestinal manifestations.", "protein": "HLA-DRB1*01:03", "relationship_type": "causal", "source_pmcid": "PMC12347028" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation impacts peptide-binding groove structure.", "mechanism": "Associated with pediatric-onset UC and extensive colitis.", "protein": "HLA-DRB1*13:01", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "Linked to more extensive disease beyond the rectum in Japanese patients.", "protein": "HLA-DRB1*08", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "medium", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "Associated with later age at diagnosis.", "protein": "HLA-DRB1*09", "relationship_type": "biomarker", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation stabilizes HLA molecule for antigen presentation.", "mechanism": "Consistently associated with UC across multiple populations.", "protein": "HLA-DRB1*1502", "relationship_type": "causal", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Ankylosing Spondylitis", "glycan_involvement": "Glycosylation affects folding and surface expression.", "mechanism": "Strongly linked to disease susceptibility and earlier onset.", "protein": "HLA-B27", "relationship_type": "causal", "source_pmcid": "PMC12347028" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation alters peptide-binding groove conformation.", "mechanism": "Potentially reduces likelihood of ADA formation and therapy resistance due to less efficient antigen presentation.", "protein": "HLA-DQA1*03", "relationship_type": "protective", "source_pmcid": "PMC12347028" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "CD44 is a glycoprotein; its interaction with hyaluronic acid depends on glycosylation.", "mechanism": "CD44 is highly expressed in TNBC cells (MDA-MB-231), marking mesenchymal and stem-like phenotypes, and is linked to migration, invasion, and drug resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "CD44 glycosylation is essential for HA binding and cell migration.", "mechanism": "Fumiquinazoline F reduces CD44 protein stability, decreasing cell migration and adhesion to hyaluronic acid, suggesting CD44 as a therapeutic target.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "E-cadherin is glycosylated, which affects its stability and cell-cell adhesion.", "mechanism": "Low E-cadherin is characteristic of EMT and aggressive TNBC; fumiquinazoline F increases E-cadherin protein, reverting cells to a less malignant phenotype.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "High vimentin marks EMT and metastatic potential; fumiquinazoline F decreases vimentin protein levels, reducing migration.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Cancer stem cell phenotype", "glycan_involvement": "Glycosylation modulates CD44 function and ligand binding.", "mechanism": "CD44 marks cancer stem cells, conferring self-renewal, migration, and drug resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation required for HA binding and migration.", "mechanism": "CD44 promotes cell migration, adhesion, and survival; its reduction by fumiquinazoline F impairs these processes.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347039" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation status may affect degradation and function.", "mechanism": "Reduction of CD44 by fumiquinazoline F and MG132 synergistically inhibits cell growth and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12347039" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation stabilizes E-cadherin at the membrane.", "mechanism": "Increasing E-cadherin protein by fumiquinazoline F reverses EMT, reducing malignancy.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates CD44-mediated signaling.", "mechanism": "CD44 expression correlates with poor prognosis, metastasis, and therapy resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation necessary for HA binding.", "mechanism": "CD44 reduction impairs adhesion to hyaluronic acid, limiting metastatic spread.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347039" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation affects CRP stability and function as an inflammation marker.", "mechanism": "Serum CRP levels decrease with krill oil supplementation, indicating reduced inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347114" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor binding.", "mechanism": "Krill oil and fish oil reduce TNF-\u03b1 expression, mediating anti-inflammatory effects.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation influences IL-6 stability and receptor interaction.", "mechanism": "KO and FO modulate IL-6 levels, contributing to reduced joint inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation critical for ICAM-1 cell adhesion and inflammatory signaling.", "mechanism": "Astaxanthin (from KO) reduces ICAM-1 expression, improving blood-brain barrier integrity and reducing neuroinflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation required for TLR4 surface expression and LPS binding.", "mechanism": "KO inhibits TLR4-mediated macrophage activation, reducing cytokine release.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation regulates NF-\u03baB nuclear translocation and activity.", "mechanism": "KO and FO inhibit NF-\u03baB activation, lowering pro-inflammatory gene expression.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "N-glycosylation affects COX-2 enzyme stability and activity.", "mechanism": "KO and FO suppress COX-2 expression, reducing prostaglandin-mediated inflammation.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates MCP-1 secretion and chemotactic activity.", "mechanism": "KO and FO reduce MCP-1 expression, decreasing macrophage infiltration in adipose tissue.", "protein": "MCP-1/CCL2", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation regulate APP cleavage and aggregation.", "mechanism": "KO reduces amyloid \u03b2 accumulation by modulating APP processing and neuroinflammation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "medium", "disease": "Gastric ulcer", "glycan_involvement": "Glycosylation affects IL-1\u03b2 maturation and secretion.", "mechanism": "KO decreases IL-1\u03b2 expression, reducing gastric mucosal inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12347114" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Upregulated in muscle atrophy; flavonoids (quercetin, rutin, eriocitrin, naringin, baicalin) suppress its expression to prevent muscle loss.", "protein": "Atrogin-1 (FBXO32)", "protein_enriched": { "function": "", "gene_name": "Ube-1c", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9R1R5" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Upregulated during muscle wasting; suppressed by flavonoids to protect muscle mass.", "protein": "MuRF1 (TRIM63)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Promotes inflammation and muscle degradation; inhibited by quercetin, rutin, baicalin, genkwanin, isoschaftoside.", "protein": "NF-\u03baB (RELA)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Myostatin is N-glycosylated, which affects secretion and activity.", "mechanism": "Negative regulator of muscle growth; quercetin glycosides suppress myostatin signaling to prevent atrophy.", "protein": "Myostatin (GDF8)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "GLUT4 is N-glycosylated, required for proper trafficking.", "mechanism": "Facilitates glucose uptake in muscle; kaempferol glycosides, rutin, genkwanin promote GLUT4 translocation to improve insulin sensitivity.", "protein": "GLUT4 (SLC2A4)", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of", "gene_name": "SLC2A4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P14672" }, "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Regulates metabolic and stress responses; kaempferol 3-O-rutinoside upregulates SIRT1 to enhance glucose uptake and muscle function.", "protein": "SIRT1", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Promotes mitochondrial biogenesis; upregulated by rutin, naringin, puerarin to improve muscle energy metabolism.", "protein": "PGC-1\u03b1 (PPARGC1A)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Muscle atrophy", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Activates atrophy genes (Atrogin-1, MuRF1); inhibited by rutin, genkwanin to prevent muscle loss.", "protein": "FOXO3", "protein_enriched": { "function": "Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed", "gene_name": "FOXO3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G81295CK" ], "uniprot_id": "O43524" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "Promotes muscle regeneration; upregulated by isoschaftoside, rutin, kaempferol to enhance myogenesis.", "protein": "MyoD", "protein_enriched": { "function": "Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYF5 and MYOG, co-occupies muscle-specific gen", "gene_name": "MYOD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15172" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12347122" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "IL-6 is N-glycosylated, affecting secretion and stability.", "mechanism": "Pro-inflammatory cytokine; elevated in sarcopenia, suppressed by rutin and other flavonoids to reduce muscle inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347122" }, { "confidence": "high", "disease": "Cancer (multiple types)", "glycan_involvement": "N-glycosylation affects protein stability and membrane localization, influencing drug efflux activity.", "mechanism": "ABCG2 overexpression and certain SNPs (V12M, Q141K, 12M/141K haplotype) confer multidrug resistance by exporting anticancer drugs from cancer cells.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347123" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "N-glycosylation may affect transporter function and uric acid export.", "mechanism": "Q141K and 12M/141K haplotype reduce uric acid transport, increasing susceptibility to gout.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "causal", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "N-glycosylation influences ABCG2 stability and function.", "mechanism": "ABCG2 SNPs (V12M, Q141K) associated with altered drug and metabolite transport, impacting disease risk.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Idiopathic male infertility", "glycan_involvement": "N-glycosylation may modulate transporter activity.", "mechanism": "ABCG2 variants linked to altered transport of endogenous substrates affecting fertility.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation affects ABCG2 localization and function in placenta.", "mechanism": "ABCG2 SNPs associated with altered placental transport of substrates, influencing disease risk.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation impacts transporter stability and activity.", "mechanism": "ABCG2 variants may affect drug and metabolite transport relevant to diabetes pathophysiology.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "high", "disease": "Anticancer drug resistance (in cancer)", "glycan_involvement": "N-glycosylation required for proper membrane localization and function.", "mechanism": "ABCG2 (12M/141K) haplotype increases resistance to mitoxantrone and SN-38 by enhancing drug efflux.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "causal", "source_pmcid": "PMC12347123" }, { "confidence": "high", "disease": "Breast carcinoma", "glycan_involvement": "N-glycosylation affects ABCG2 stability and drug resistance.", "mechanism": "ABCG2 expression and SNPs predict disease progression and treatment response.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "N-glycosylation modulates transporter function.", "mechanism": "ABCG2 variants and expression levels associated with disease progression and therapy response.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "medium", "disease": "Hepatoma", "glycan_involvement": "N-glycosylation influences ABCG2 activity.", "mechanism": "ABCG2 SNPs and expression linked to disease progression and drug response.", "protein": "ABCG2 (BCRP/MXR)", "relationship_type": "biomarker", "source_pmcid": "PMC12347123" }, { "confidence": "high", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "CYP7A1 is not a glycoprotein; no direct glycosylation involvement.", "mechanism": "Polymorphism rs3808607 (G allele) increases ICP risk, likely via increased bile acid synthesis.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "RXRA is not a glycoprotein; no direct glycosylation involvement.", "mechanism": "rs11381416 A insertion associated with higher bile acids, ALT, AST in ICP women.", "protein": "RXRA", "relationship_type": "biomarker", "source_pmcid": "PMC12347146" }, { "confidence": "high", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "BSEP is N-glycosylated; glycosylation is critical for membrane localization and function.", "mechanism": "Polymorphisms in ABCB11 (BSEP) impair bile acid export, contributing to ICP.", "protein": "BSEP", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "high", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "MDR3 is N-glycosylated; glycosylation affects stability and canalicular targeting.", "mechanism": "Polymorphisms in ABCB4 (MDR3) reduce phosphatidylcholine transport, increasing bile toxicity.", "protein": "MDR3", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "FXR is not a glycoprotein; no direct glycosylation involvement.", "mechanism": "FXR variants (e.g., rs56163822) reduce receptor activity, impairing bile acid homeostasis.", "protein": "FXR", "protein_enriched": { "function": "Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in", "gene_name": "NR1H4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96RI1" }, "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "PPARA is not a glycoprotein; no direct glycosylation involvement.", "mechanism": "PPARA L162V variant associated with increased triglycerides, cholesterol, and diabetes risk.", "protein": "PPARA", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "medium", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "MRP2 is N-glycosylated; glycosylation is essential for canalicular membrane targeting.", "mechanism": "ABCC2 (MRP2) variants reduce bile acid and organic anion excretion, contributing to ICP.", "protein": "MRP2", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "medium", "disease": "Familial Intrahepatic Cholestasis", "glycan_involvement": "FIC1 is N-glycosylated; glycosylation affects protein folding and function.", "mechanism": "ATP8B1 mutations cause defective bile acid transport, leading to cholestasis.", "protein": "FIC1", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "low", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "NTCP is N-glycosylated; glycosylation is required for cell surface expression.", "mechanism": "NTCP mediates hepatic bile acid uptake; dysfunction may contribute to cholestasis.", "protein": "NTCP", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "low", "disease": "Intrahepatic Cholestasis of Pregnancy (ICP)", "glycan_involvement": "ASBT is N-glycosylated; glycosylation is important for transporter stability.", "mechanism": "ASBT regulates intestinal bile acid reabsorption; altered function may affect bile acid pool.", "protein": "ASBT", "relationship_type": "causal", "source_pmcid": "PMC12347146" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may regulate SQSTM1 stability and autophagic cargo recognition.", "mechanism": "Upregulation promotes autophagy, facilitating viral replication in Sf9 cells.", "protein": "Sequestosome 1 (SQSTM1/p62)", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation affects transporter localization and function.", "mechanism": "Upregulation may enhance efflux of antiviral compounds, promoting viral replication.", "protein": "MRP4/ABCC4", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation modulates enzyme activity and substrate specificity.", "mechanism": "Upregulation reduces oxidative stress, promoting viral replication.", "protein": "UGT2B15-like", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may influence GST stability and detoxification capacity.", "mechanism": "Upregulation regulates glutathione levels, facilitating viral proliferation.", "protein": "GST", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may affect enzyme activity and cellular localization.", "mechanism": "Upregulation inhibits apoptosis, promoting viral replication.", "protein": "CYP9E2", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may regulate enzyme stability and hormone biosynthesis.", "mechanism": "Upregulation increases juvenile hormone, prolonging pupation and enhancing viral replication.", "protein": "JHAMT", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may modulate enzyme activity.", "mechanism": "Upregulation alters juvenile hormone degradation, affecting development and viral replication.", "protein": "JHE", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation affects transporter function and membrane localization.", "mechanism": "Upregulation increases trehalose transport, providing energy for viral replication.", "protein": "Tret1", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may regulate enzyme activity.", "mechanism": "Upregulation enhances glycerol metabolism, supporting energy needs for viral replication.", "protein": "GK", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "medium", "disease": "DnCPV-23 infection", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "Upregulation aids detoxification, supporting cell survival and viral replication.", "protein": "CYP6B7", "relationship_type": "causal", "source_pmcid": "PMC12347268" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CD26 is a glycoprotein; glycosylation supports its cell surface localization and function.", "mechanism": "CD26 is highly expressed in CRC tissues and correlates with tumor aggressiveness and poor prognosis.", "protein": "CD26 (DPP-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Colorectal cancer stem cell-driven metastasis", "glycan_involvement": "Glycosylation enables CD26\u2019s interactions with ECM and other membrane proteins.", "mechanism": "CD26 marks CSCs with high metastatic potential and drives EMT, migration, and invasion.", "protein": "CD26 (DPP-4)", "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Liver metastasis (from CRC)", "glycan_involvement": "Glycosylation is required for CD26\u2019s cell surface expression and metastatic function.", "mechanism": "CD26+ CRC cells initiate liver metastasis in vivo; anti-CD26 antibody suppresses this process.", "protein": "CD26 (DPP-4)", "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Targeting glycosylated CD26 on cell surface is essential for antibody efficacy.", "mechanism": "Anti-CD26 antibody inhibits EMT, migration, invasion, and metastasis in CRC models.", "protein": "CD26 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "E-cadherin is glycosylated; glycosylation stabilizes its cell adhesion function.", "mechanism": "Upregulation of E-cadherin (epithelial marker) by anti-CD26 antibody reverses EMT.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-cadherin glycosylation affects cell motility and invasion.", "mechanism": "N-cadherin (mesenchymal marker) is downregulated by anti-CD26 antibody, suppressing EMT.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "ZEB1 is upregulated with CD26 during EMT; anti-CD26 antibody downregulates ZEB1.", "protein": "ZEB1", "protein_enriched": { "function": "Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell typ", "gene_name": "ZEB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P37275" }, "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "Twist1 is upregulated with CD26 during EMT; anti-CD26 antibody downregulates Twist1.", "protein": "Twist1", "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not specified.", "mechanism": "Snail1 is upregulated during EMT; anti-CD26 antibody downregulates Snail1.", "protein": "Snail1", "relationship_type": "causal", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation is necessary for CD26\u2019s surface expression and function.", "mechanism": "CD26 expression increases with cell confluence and correlates with EMT marker expression.", "protein": "CD26 (DPP-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12347270" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "HA binds sialic acid-containing glycoproteins on host cells.", "mechanism": "HA mediates viral attachment to host cell sialic acid glycoprotein receptors, initiating infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Inhibition of HA-sialic acid glycoprotein interaction.", "mechanism": "Conessine inhibits HA-mediated binding and entry, blocking early infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "NA acts on sialic acid residues of host glycoproteins.", "mechanism": "NA facilitates viral progeny release by cleaving sialic acid from host glycoproteins; targeted by drugs like oseltamivir.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Seasonal flu", "glycan_involvement": "Glycosylation affects HA antigenicity and immune evasion.", "mechanism": "HA antigenic variation drives seasonal flu epidemics.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Prevents HA interaction with host sialylated glycoproteins.", "mechanism": "Conessine blocks HA, preventing viral binding and entry, conferring protection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12347278" }, { "confidence": "medium", "disease": "Seasonal flu", "glycan_involvement": "NA glycosylation modulates enzymatic activity and immune recognition.", "mechanism": "NA antigenic variation contributes to flu strain diversity.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347278" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Not directly glycosylated; detected as a marker.", "mechanism": "NP expression indicates active viral replication.", "protein": "Nucleoprotein (NP)", "relationship_type": "biomarker", "source_pmcid": "PMC12347278" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Not directly glycosylated.", "mechanism": "M2 expression is a marker of viral infection.", "protein": "Matrix protein 2 (M2)", "protein_enriched": { "function": "Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis.", "gene_name": "M", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P06821" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347278" }, { "confidence": "medium", "disease": "Influenza A virus infection", "glycan_involvement": "Not directly glycosylated.", "mechanism": "NS1 detected in infected cells; modulates host immune response.", "protein": "Nonstructural protein 1 (NS1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Respiratory illness", "glycan_involvement": "HA binds respiratory tract sialylated glycoproteins.", "mechanism": "HA-mediated entry leads to respiratory symptoms.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347278" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Palmitoylation (lipidation) regulates glycoprotein localization/function.", "mechanism": "Palmitoylation of CD36 enhances fatty acid uptake, promoting metastasis and tumor growth.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Palmitoylation affects glycoprotein stability.", "mechanism": "ZDHHC1-mediated palmitoylation of IGF2BP1 suppresses tumorigenicity.", "protein": "IGF2BP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347385" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Palmitoylation regulates immune checkpoint glycoprotein stability.", "mechanism": "ZDHHC9-mediated palmitoylation stabilizes PD-L1, promoting tumor growth.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347385" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Palmitoylation modulates glycoprotein membrane localization.", "mechanism": "ZDHHC9 palmitoylation of GLUT1 enhances glycolysis and tumorigenesis.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "causal", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Palmitoylation affects glycoprotein stability and localization.", "mechanism": "ZDHHC12-mediated palmitoylation of CLDN3 promotes membrane localization and tumorigenesis.", "protein": "CLDN3", "relationship_type": "causal", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Palmitoylation and glycosylation regulate function.", "mechanism": "FABP4 facilitates lipid metabolism, promoting cancer cell growth and survival.", "protein": "FABP4", "protein_enriched": { "function": "Important in genetic recombination, DNA repair, and replication. Possesses pairing and strand-transfer activity. Interacts with dda and gene 32 proteins", "gene_name": "UVSX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06727" }, "relationship_type": "causal", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Renal cell carcinoma", "glycan_involvement": "Palmitoylation modulates glycoprotein signaling.", "mechanism": "ZDHHC2-mediated palmitoylation of AGK activates PI3K-AKT-mTOR signaling.", "protein": "AGK", "protein_enriched": { "function": "Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15939762). Does not phosphorylate sphi", "gene_name": "AGK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q53H12" }, "relationship_type": "causal", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Palmitoylation regulates tight junction glycoprotein localization.", "mechanism": "ZDHHC7 palmitoylation of JAM-C inhibits migration of A549 lung cancer cells.", "protein": "JAM-C", "relationship_type": "protective", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Palmitoylation affects glycoprotein polarity and tumor suppression.", "mechanism": "ZDHHC7 palmitoylation maintains SCRIB localization, suppressing oncogenic YAP activation.", "protein": "SCRIB", "protein_enriched": { "function": "Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:1696", "gene_name": "SCRIB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q14160" }, "relationship_type": "protective", "source_pmcid": "PMC12347385" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Palmitoylation modulates receptor glycoprotein function.", "mechanism": "ZDHHC13 palmitoylation of MC1R suppresses UVB-induced transformation and delays melanomagenesis.", "protein": "MC1R", "protein_enriched": { "function": "Receptor for MSH (alpha, beta and gamma) and ACTH (PubMed:11442765, PubMed:11707265, PubMed:1325670, PubMed:1516719, PubMed:8463333). The activity of this receptor is mediated by G proteins which acti", "gene_name": "MC1R", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01726" }, "relationship_type": "protective", "source_pmcid": "PMC12347385" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "CD39 is a glycoprotein; glycosylation may affect its stability and localization.", "mechanism": "CD39 is upregulated in GCSCs, promoting ATP hydrolysis to AMP, leading to increased extracellular adenosine and supporting tumor progression, recurrence, and immune suppression.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347490" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation (especially sialylation) and GPI-anchoring modulate CD73 activity and localization.", "mechanism": "CD73 catalyzes AMP to adenosine; increased AMPase activity in GCSCs (without increased expression) enhances adenosine production, contributing to chemoresistance, invasion, and immune evasion.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347490" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "ENT2 is a glycoprotein; glycosylation may affect membrane localization and transport activity.", "mechanism": "ENT2 is upregulated in GCSCs, facilitating adenosine transport and accumulation, which supports chemoresistance and tumor progression.", "protein": "ENT2", "protein_enriched": { "function": "Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:10722669, PubMed:12527552, PubMed:12590", "gene_name": "SLC29A2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q14542" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347490" }, { "confidence": "high", "disease": "Gastric cancer stem-like cell-driven recurrence", "glycan_involvement": "Glycosylation may regulate CD39 function in stem cell niches.", "mechanism": "High CD39 expression in GCSCs enables efficient ATP hydrolysis, increasing adenosine and promoting stemness, recurrence, and metastasis.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "medium", "disease": "Chemoresistance in gastric cancer", "glycan_involvement": "Post-translational glycan modifications may enhance CD73 catalytic efficiency.", "mechanism": "Elevated CD73 activity in GCSCs increases adenosine, which is linked to resistance to chemotherapy (e.g., 5-FU).", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "medium", "disease": "Chemoresistance in gastric cancer", "glycan_involvement": "Glycosylation may affect ENT2 substrate specificity and drug uptake.", "mechanism": "ENT2 upregulation in GCSCs increases adenosine transport, contributing to drug resistance.", "protein": "ENT2", "protein_enriched": { "function": "Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:10722669, PubMed:12527552, PubMed:12590", "gene_name": "SLC29A2", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q14542" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "medium", "disease": "Metastasis in gastric cancer", "glycan_involvement": "Glycosylation and membrane localization may enhance CD73 function in metastatic niches.", "mechanism": "CD73-generated adenosine promotes cell migration and invasion, facilitating metastasis.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "high", "disease": "Immunosuppression in gastric cancer", "glycan_involvement": "Glycosylation may stabilize CD73 and increase its immunosuppressive activity.", "mechanism": "CD73-derived adenosine suppresses antitumor immune responses in the tumor microenvironment.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation may regulate CD39 activity in neural stem cell niches.", "mechanism": "High CD39 expression in glioma stem cells correlates with increased adenosine and tumor aggressiveness.", "protein": "CD39", "protein_enriched": { "function": "Catalyzes the hydrolysis of both di- and triphosphate nucleotides (NDPs and NTPs) and hydrolyze NTPs to nucleotide monophosphates (NMPs) in two distinct successive phosphate-releasing steps, with NDPs", "gene_name": "ENTPD1", "glycan_count": 30, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G27947YN", "G28622IK", "G43223CG", "G45395BF", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G80075MS", "G90382BL", "G93718GY", "G00912UN", "G01650EU", "G02815KT", "G28541PG", "G37399XV", "G39446WN", "G41840AI", "G59924QI", "G72747WU", "G82463GQ", "G10819WX", "G27058EU", "G40926MX", "G60033FS", "G62765YT", "G70441OD", "G86880BF", "G49108TO" ], "uniprot_id": "P49961" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347490" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation and GPI-anchoring are critical for CD73 function in ovarian cancer stem cells.", "mechanism": "CD73 promotes sphere formation and tumor initiation in ovarian carcinoma cells.", "protein": "CD73", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P45373" }, "relationship_type": "causal", "source_pmcid": "PMC12347490" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Polysialylation (PSA) of NCAM enhances cell migration, plasticity, and immune evasion.", "mechanism": "PSA-NCAM is upregulated in GBM, especially under nutrient deprivation, correlating with tumor aggressiveness and poor prognosis.", "protein": "NCAM (Neural Cell Adhesion Molecule)", "relationship_type": "biomarker", "source_pmcid": "PMC12347492" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Catalyzes \u03b12,8-linked polysialic acid addition to NCAM.", "mechanism": "Upregulation of ST8SiaIV drives PSA-NCAM synthesis under nutrient stress, promoting GBM cell migration and stemness.", "protein": "ST8SiaIV (Polysialyltransferase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347492" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Removes sialic acids, enabling their reuse for polysialylation.", "mechanism": "NEU1 activity is essential for recycling sialic acids from degraded glycoproteins, sustaining PSA synthesis during autophagy.", "protein": "NEU1 (Neuraminidase 1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347492" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "CMP-sialic acid is the donor substrate for glycosylation.", "mechanism": "CMAS provides activated sialic acid for sialyltransferases, supporting high sialylation in GBM.", "protein": "CMAS (CMP-sialic acid synthetase)", "protein_enriched": { "function": "Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions (PubMed:22460716). Mediates chloride-dependent transport of urate (PubMed:", "gene_name": "SLC17A4", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9Y2C5" }, "relationship_type": "causal", "source_pmcid": "PMC12347492" }, { "confidence": "medium", "disease": "Brain metastasis", "glycan_involvement": "Adds \u03b12,6-linked sialic acids to O-glycans.", "mechanism": "ST6GalNAC5 expression in breast cancer cells mediates brain metastasis by enhancing blood\u2013brain barrier crossing.", "protein": "ST6GalNAC5", "relationship_type": "causal", "source_pmcid": "PMC12347492" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Adds \u03b12,3-linked sialic acids to glycoproteins.", "mechanism": "High ST3Gal1 expression is associated with GBM and may contribute to invasive behavior.", "protein": "ST3Gal1", "relationship_type": "biomarker", "source_pmcid": "PMC12347492" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Adds \u03b12,6-linked sialic acids to N-glycans.", "mechanism": "Elevated ST6Gal1 in GBM supports increased sialylation, potentially aiding immune evasion.", "protein": "ST6Gal1", "relationship_type": "biomarker", "source_pmcid": "PMC12347492" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Indirect; autophagy facilitates sialic acid recycling for glycosylation.", "mechanism": "LC3 co-localizes with PSA in GBM tissues, indicating autophagy activation in regions of high PSA expression.", "protein": "LC3", "relationship_type": "biomarker", "source_pmcid": "PMC12347492" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Blocking PSA addition to NCAM impairs tumor cell plasticity.", "mechanism": "Inhibition of NCAM polysialylation (e.g., by F-NANA) reduces GBM cell migration and stem-like properties.", "protein": "NCAM (Neural Cell Adhesion Molecule)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347492" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Polysialylation marks cells with high migratory and stem-like potential.", "mechanism": "PSA-NCAM is highly expressed around necrotic regions and pseudo-palisading cells in GBM tissue, marking aggressive tumor zones.", "protein": "NCAM (Neural Cell Adhesion Molecule)", "relationship_type": "biomarker", "source_pmcid": "PMC12347492" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Crocin is a glycosylated molecule (crocin = beta-D-glucosyl trans-crocetin) that mimics glycan interactions in the DNMT1 active site.", "mechanism": "Crocin inhibits DNMT1, potentially silencing oncogenic methylation patterns.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Glycosylation of crocin enhances its binding to DNMT1.", "mechanism": "Crocin-mediated DNMT1 inhibition may delay age-related DNA methylation changes.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Crocin\u2019s glycosylation facilitates stable binding to HDAC2.", "mechanism": "Crocin and crocetin inhibit HDAC2, restoring redox homeostasis and protecting against monocyte dysfunction.", "protein": "HDAC2", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epige", "gene_name": "HDAC2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q92769" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation of crocin enhances HDAC2 inhibition.", "mechanism": "HDAC2 inhibition by crocin/crocetin mitigates high-fat diet-induced hypertension.", "protein": "HDAC2", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epige", "gene_name": "HDAC2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q92769" }, "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Crocin\u2019s glycosylation promotes SIRT1 activation.", "mechanism": "Crocin, crocetin, and picrocrocin activate SIRT1, increasing SIRT1 gene expression and improving cardiovascular health.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Glycosylation of crocin/crocetin stabilizes SIRT1 binding.", "mechanism": "Activation of SIRT1 by saffron glycosides supports anti-aging effects via downstream targets (FOXO, p53, NF-\u03baB).", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Retinal degeneration", "glycan_involvement": "Glycosylated crocin may mediate SIRT1 activation.", "mechanism": "Saffron extract enhances SIRT1 expression, reducing age-related retinal degeneration.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Crocin glycosylation may facilitate SIRT1 activation.", "mechanism": "Saffron increases SIRT1, attenuating NLRP3 inflammasome activation in neuronal cells.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Crocin\u2019s glycosylation is key for DNMT1 binding.", "mechanism": "DNMT1 inhibition by crocin may reduce methylation-linked diabetic pathology.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "protective", "source_pmcid": "PMC12347544" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation of crocin enhances HDAC2 inhibition.", "mechanism": "Crocin/crocetin inhibit HDAC2, suppressing cancer cell proliferation.", "protein": "HDAC2", "protein_enriched": { "function": "Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epige", "gene_name": "HDAC2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "Q92769" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347544" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "sST2 is a glycoprotein; glycosylation may affect its stability and function.", "mechanism": "Elevated sST2 levels reflect increased vascular fibrosis and arterial stiffness in T2DM.", "protein": "soluble ST2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC12347584" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation of sST2 may modulate its decoy receptor function.", "mechanism": "Higher sST2 levels are associated with more advanced CAD and vascular aging.", "protein": "soluble ST2 (sST2)", "relationship_type": "biomarker", "source_pmcid": "PMC12347584" }, { "confidence": "high", "disease": "Arterial Stiffness (AS)", "glycan_involvement": "Glycosylation may influence sST2's interaction with IL-33.", "mechanism": "sST2 promotes vascular fibrosis by neutralizing IL-33, leading to increased AS.", "protein": "soluble ST2 (sST2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347584" }, { "confidence": "high", "disease": "Arterial Stiffness (AS)", "glycan_involvement": "Non-enzymatic glycation of proteins (AGE formation) is central.", "mechanism": "AGEs cross-link collagen and proteoglycans, reducing vascular elasticity and increasing AS.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycation alters protein structure and function.", "mechanism": "AGEs promote oxidative stress, inflammation, and VSMC proliferation, accelerating atherogenesis.", "protein": "Advanced Glycation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "medium", "disease": "Vascular Fibrosis", "glycan_involvement": "RAGE is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "AGE-RAGE interaction triggers profibrotic signaling (TGF-\u03b2, CTGF) and ECM protein production.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "medium", "disease": "Arterial Stiffness (AS)", "glycan_involvement": "IL-33 is glycosylated, which may affect receptor interaction.", "mechanism": "IL-33 binding to ST2L attenuates fibrosis and arterial stiffening; sST2 blocks this effect.", "protein": "Interleukin-33 (IL-33)", "relationship_type": "protective", "source_pmcid": "PMC12347584" }, { "confidence": "medium", "disease": "Arterial Stiffness (AS)", "glycan_involvement": "Collagen glycosylation affects fibril formation and stiffness.", "mechanism": "Increased collagen deposition (stimulated by sST2 and profibrotic mediators) stiffens arteries.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "medium", "disease": "Vascular Fibrosis", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation modulates ECM interactions.", "mechanism": "sST2 stimulates fibronectin production, contributing to ECM expansion and fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "medium", "disease": "Vascular Fibrosis", "glycan_involvement": "TGF-\u03b2 is glycosylated, which may affect secretion and activity.", "mechanism": "AGE-RAGE signaling increases TGF-\u03b2, promoting ECM protein synthesis and fibrosis.", "protein": "Transforming Growth Factor-beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12347584" }, { "confidence": "high", "disease": "Acute ischemic stroke", "glycan_involvement": "Glycosylation is essential for protein stability and function as a therapeutic agent.", "mechanism": "Inhibits neutrophil activity to reduce inflammation and tissue damage during stroke.", "protein": "Neutrophil inhibitory glycoprotein (UK-279,276)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347587" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation increases half-life and reduces immunogenicity, enabling weekly dosing.", "mechanism": "GLP-1 receptor agonist improves glycemic control by enhancing insulin secretion.", "protein": "Dulaglutide (LY2189265)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347587" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Increased N-glycosylation observed in pathogenic FLCs.", "mechanism": "Monoclonal FLC \u03ba is elevated due to plasma cell expansion; used for diagnosis and monitoring.", "protein": "Immunoglobulin Free Light Chain (FLC) \u03ba", "relationship_type": "biomarker", "source_pmcid": "PMC12347604" }, { "confidence": "high", "disease": "AL Amyloidosis", "glycan_involvement": "N-glycosylation increases aggregation propensity.", "mechanism": "Amyloidogenic \u03bb FLCs misfold and deposit as \u03b2-sheet-rich fibrils in tissues.", "protein": "Immunoglobulin Free Light Chain (FLC) \u03bb", "relationship_type": "causal", "source_pmcid": "PMC12347604" }, { "confidence": "high", "disease": "Light Chain Deposition Disease (LCDD)", "glycan_involvement": "Unusual FLC size and increased N-glycosylation linked to deposition.", "mechanism": "Pathogenic \u03ba FLCs deposit as amorphous aggregates in kidney, causing organ dysfunction.", "protein": "Immunoglobulin Free Light Chain (FLC) \u03ba", "relationship_type": "causal", "source_pmcid": "PMC12347604" }, { "confidence": "medium", "disease": "Autoimmune Diseases (e.g., SLE, RA)", "glycan_involvement": "Not specified.", "mechanism": "Polyclonal FLC elevation correlates with disease activity.", "protein": "Immunoglobulin Free Light Chain (FLC) \u03ba/\u03bb", "relationship_type": "biomarker", "source_pmcid": "PMC12347604" }, { "confidence": "high", "disease": "Colitis-associated Cancer", "glycan_involvement": "Not specified.", "mechanism": "Promotes inflammation and tumorigenesis via inflammasome activation and neutrophil recruitment.", "protein": "V\u03ba4-1/J\u03ba3 FLC (non-B cell-derived)", "relationship_type": "causal", "source_pmcid": "PMC12347604" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Stabilizes ETFA, enhancing fatty acid \u03b2-oxidation and tumor growth.", "protein": "Ig\u03ba (non-B cell-derived)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347604" }, { "confidence": "high", "disease": "Colon Cancer", "glycan_involvement": "Not specified.", "mechanism": "Acts as integrin \u03b21 ligand, activates FAK/Src signaling, promotes invasion/metastasis.", "protein": "V\u03ba4-1/J\u03ba3 FLC (non-B cell-derived)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347604" }, { "confidence": "medium", "disease": "Cervical Cancer", "glycan_involvement": "Not specified.", "mechanism": "Interacts with RPL7, RPS3, H1-5, H1-6 to promote oncogenic gene activation, DNA repair disruption, and metastasis.", "protein": "Ig\u03bb (tumor-derived)", "relationship_type": "causal", "source_pmcid": "PMC12347604" }, { "confidence": "medium", "disease": "Sarcoma", "glycan_involvement": "Not specified.", "mechanism": "Correlates with proliferation markers (PCNA, Ki-67, cyclin D1); promotes tumor cell proliferation.", "protein": "Ig\u03ba (non-B cell-derived)", "relationship_type": "causal", "source_pmcid": "PMC12347604" }, { "confidence": "medium", "disease": "Nonallergic Rhinitis", "glycan_involvement": "Not specified.", "mechanism": "Elevated FLCs in nasal mucosa promote mast cell activation and local inflammation.", "protein": "Immunoglobulin Free Light Chain (FLC)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347604" }, { "confidence": "medium", "disease": "Schistosomiasis (Schistosoma mansoni infection)", "glycan_involvement": "LCAT is a glycoprotein; glycosylation may affect its stability and activity.", "mechanism": "Decreased LCAT activity leads to reduced cholesterol esterification and total cholesterol in infected individuals.", "protein": "Lecithin-cholesterol acyltransferase (LCAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "GGT is a glycoprotein; glycosylation may modulate its serum levels.", "mechanism": "Elevated GGT correlates with high parasite load and hepatic granulomas.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "high", "disease": "Schistosomiasis (Schistosoma mansoni infection)", "glycan_involvement": "PI is a glycolipid; its glycan moiety is essential for membrane and signaling functions.", "mechanism": "Decreased PI species in high parasite load, possibly due to consumption by parasite for tegument integrity and signaling.", "protein": "Phosphatidylinositol (PI)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "medium", "disease": "Schistosomiasis (Schistosoma mansoni infection)", "glycan_involvement": "TAGs are carried by glycoprotein-rich lipoproteins; glycosylation affects transport.", "mechanism": "Increased TAG species in high parasite load, reflecting host lipid mobilization for parasite egg production.", "protein": "Triacylglycerol (TAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "medium", "disease": "Schistosomiasis (Schistosoma mansoni infection)", "glycan_involvement": "PC is a glycolipid; glycan structure affects membrane properties.", "mechanism": "PC is the most abundant phospholipid in all groups; altered metabolism may reflect infection status.", "protein": "Phosphatidylcholine (PC)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "low", "disease": "Hepatic fibrosis", "glycan_involvement": "HexCer is a glycosphingolipid; glycan moiety is critical for cell signaling.", "mechanism": "HexCer subclass is abundant in infected individuals, similar to severe fibrosis in HCV infection.", "protein": "Hexosylceramide (HexCer)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "low", "disease": "Schistosomiasis (Schistosoma mansoni infection)", "glycan_involvement": "Enzyme glycosylation may affect activity and stability.", "mechanism": "Reduced hepatic expression impairs fatty acid metabolism in infected mice.", "protein": "Acetyl coenzyme A acyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12347608" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation may influence GGT secretion and function.", "mechanism": "GGT elevation may result from biliary compression due to granuloma formation.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "Glycan moiety involved in signaling and membrane dynamics.", "mechanism": "Altered PI metabolism may reflect immune-metabolic disturbances in severe infection.", "protein": "Phosphatidylinositol (PI)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "TAG transport depends on glycoprotein-rich lipoproteins.", "mechanism": "Altered TAG levels indicate metabolic disturbance in severe schistosomiasis.", "protein": "Triacylglycerol (TAG)", "relationship_type": "biomarker", "source_pmcid": "PMC12347608" }, { "confidence": "high", "disease": "Renal Oncocytoma", "glycan_involvement": "LAMP1 is a heavily glycosylated lysosomal membrane protein; glycosylation is essential for its stability and function.", "mechanism": "Loss of LAMP1 expression leads to lysosomal dysfunction, impairing mitophagy and causing mitochondrial accumulation.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "high", "disease": "Renal Oncocytoma", "glycan_involvement": "Change in LAMP2 glycosylation pattern (increase in partially glycosylated form) disrupts lysosomal trafficking/function.", "mechanism": "Altered glycosylation and subcellular distribution of LAMP2 are associated with lysosomal dysfunction and defective mitophagy.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "medium", "disease": "Renal Oncocytoma", "glycan_involvement": "Cathepsin B is glycosylated for lysosomal targeting; loss may reflect lysosomal dysfunction.", "mechanism": "Reduced cathepsin B impairs lysosomal proteolytic activity, contributing to defective mitophagy.", "protein": "Cathepsin B", "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "high", "disease": "Renal Oncocytoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Accumulation of p62 indicates autophagy inhibition and defective lysosomal degradation.", "protein": "SQSTM1/p62", "relationship_type": "biomarker", "source_pmcid": "PMC12347756" }, { "confidence": "medium", "disease": "Birt\u2013Hogg\u2013Dube (BHD) Kidney Cancer", "glycan_involvement": "Glycosylation changes may contribute to lysosomal defects.", "mechanism": "LAMP2 dysfunction is implicated in lysosomal impairment in BHD kidney tumors with oncocytic phenotype.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", "G26330YA", "G27058EU", "G27915IV", "G27947YN", "G28681TP", "G29545VG", "G29580WD", "G30740WO", "G31309XD", "G31986NC", "G33416PL", "G35029YA", "G35541EV", "G36442WJ", "G37509XX", "G37818NZ", "G37881RL", "G37995HC", "G39471UU", "G40574BA", "G40926MX", "G41071NU", "G41882MT", "G43669FQ", "G43769HG", "G44753VC", "G45395BF", "G45526EA", "G45883VE", "G46450MZ", "G47518TP", "G48414YA", "G49755GI", "G49906RN", "G50427EO", "G50856PC", "G52527GH", "G53075ES", "G55132BD", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57888GL", "G58087IP", "G59536GA", "G59626AS", "G60033FS", "G60177UT", "G60967DT", "G62461SM", "G62765YT", "G63040RU", "G64394MX", "G65184UU", "G65414LI", "G66088HZ", "G66163OV", "G66537LK", "G68490OW", "G69521XL", "G69834CE", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71463BG", "G72787SB", "G72790NZ", "G75568BH", "G75983OB", "G76868JS", "G79286RS", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G85554PZ", "G86795LJ", "G86880BF", "G89045VA", "G89827JR", "G92081HT", "G94665LC", "G94831VI", "G95133RI", "G95865ZB", "G96577RX", "G98611JV", "G99668VU", "G99679NM", "G01485JJ", "G11314AS", "G11870QZ", "G12313PD", "G14994KB", "G23719VF", "G29299MO", "G29880MM", "G34617SM", "G36379GD", "G37399XV", "G39446WN", "G44215PV", "G47012YE", "G47448YK", "G47644PP", "G47950XN", "G48584BU", "G55383ZG", "G59924QI", "G62894KT", "G64527OM", "G70101JE", "G70441OD", "G80223IX", "G80479JV", "G82119TF", "G84820NF", "G90659AW", "G92050GC", "G92275SC", "G02886BB", "G28622IK", "G32788FZ", "G40834TG", "G42124LM", "G58954YZ", "G59324HL", "G67164EE", "G74381CZ", "G84862VB", "G93718GY", "G95046LV", "G95177YH", "G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "medium", "disease": "Translocation RCC", "glycan_involvement": "Glycosylation status may affect LAMP2 function.", "mechanism": "LAMP2 and TFEB pathway dysregulation contribute to lysosomal dysfunction in translocation RCC with oncocytic features.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", "G03644CB", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08918WF", "G09700PF", "G09831WQ", "G10486CT", "G10846ZT", "G11115RO", "G11629QQ", "G12341GU", "G13131HA", "G13191RB", "G13694XX", "G13910DJ", "G14547CB", "G14669DU", "G18647XP", "G20528HD", "G22310AV", "G25079LO", 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biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", 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"G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "medium", "disease": "Renal Oncocytoma", "glycan_involvement": "TFEB is not a glycoprotein; no direct glycan involvement.", "mechanism": "Impaired TFEB-mediated lysosome biogenesis leads to lysosomal loss and defective mitophagy.", "protein": "TFEB", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943", "gene_name": "TFEB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "P19484" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "medium", "disease": "Renal Oncocytoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Loss of Complex I subunit NDUFB8 impairs mitochondrial respiration, triggering compensatory mitochondrial biogenesis and defective mitophagy.", "protein": "NDUFB8", "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "low", "disease": "Renal Failure", "glycan_involvement": "Altered glycosylation may affect LAMP2 function.", "mechanism": "LAMP2 dysfunction may contribute to lysosomal impairment and renal parenchymal loss in renal oncocytosis.", "protein": "LAMP2", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:", "gene_name": "LAMP2", "glycan_count": 313, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00912UN", "G01160VV", "G02528FI", "G03461SC", 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"G57321FI", "G00031MO", "G64973KT", "G49108TO", "G18903CG", "G66538GV", "G05724UK", "G40379SA", "G02030ZB", "G04854VP", "G10488MI", "G10773YW", "G15664MX", "G16125XL", "G23294PN", "G23863VK", "G30970QQ", "G32926LW", "G41247ZX", "G67031OU", "G72747WU", "G72797UR", "G73686WG", "G74724QE", "G77547TA", "G77669RF", "G90093AU", "G94470IW", "G02315DX", "G02815KT", "G05049YU", "G06110VR", "G10819WX", "G18183SM", "G20210JR", "G20312EM", "G20425TQ", "G22589VJ", "G23453IV", "G25379SA", "G25418HZ", "G25451PN", "G26403SG", "G27126ED", "G30221QT", "G30769VJ", "G31852PQ", "G31916IQ", "G39595FH", "G43223CG", "G43734MM", "G45504EY", "G46902YN", "G51640FO", "G63041LO", "G65019XG", "G66933CM", "G72291OX", "G76417NN", "G77582RK", "G78649WQ", "G82463GQ", "G83229XP", "G87123QX", "G87661QW", "G89098OM", "G90382BL", "G92135MA", "G92597CK", "G22625SJ", "G26759AS", "G31596VW", "G46687AB", "G50045TK", "G65092SV", "G66621EA", "G74430RZ", "G76915KR", "G81295CK", "G86234IN", "G96416FQ", "G00406II", "G01650EU", "G03574QJ", "G04657PL", "G06231AO", "G08290VR", "G08293MJ", "G09197ZW", "G16175ZV", "G23984SE", "G25637MV", "G28541PG", "G31544HA", "G33609NS", "G39188ZX", "G39619TI", "G41126SR", "G46691LC", "G49018RC", "G49955PK", "G50372IH", "G54010QB", "G56610MH", "G56784JY", "G60834IK", "G60923RB", "G62595EF", "G72735IY", "G76295SF", "G79568CQ", "G81124ET", "G83460ZZ", "G85269DF", "G87051GH", "G92062TF", "G92406TI", "G96091TT", "G10019LZ", "G14260UH", "G03930BU", "G14972EH", "G15169WU", "G31028YV", "G34989PA", "G37412TK", "G47702MW", "G51653BI", "G63381RX", "G63980BQ", "G64409MC", "G66760KM", "G70375MX", "G71784JC", "G72667IM", "G73430PD", "G80333GO", "G87389XI", "G90734RJ", "G91473PK", "G80770LV", "G29931IJ", "G63628AV" ], "uniprot_id": "P13473" }, "relationship_type": "causal", "source_pmcid": "PMC12347756" }, { "confidence": "high", "disease": "Alagille syndrome (ALGS)", "glycan_involvement": "Jagged1 is a glycoprotein; glycosylation is essential for Notch ligand-receptor interactions.", "mechanism": "Pathogenic variants in JAG1 disrupt Notch signaling, leading to multisystem defects.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "high", "disease": "Alagille syndrome (ALGS)", "glycan_involvement": "NOTCH2 is a glycoprotein; glycosylation modulates receptor function.", "mechanism": "Pathogenic variants in NOTCH2 impair Notch signaling, causing ALGS with distinct features.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "high", "disease": "Cholestasis", "glycan_involvement": "Glycosylation affects Jagged1 stability and signaling in bile duct development.", "mechanism": "Jagged1 mutations cause bile duct paucity, leading to impaired bile flow.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "high", "disease": "Congenital heart defects", "glycan_involvement": "Glycosylation modulates ligand-receptor binding in cardiac morphogenesis.", "mechanism": "Jagged1-mediated Notch signaling is required for cardiac outflow tract and valve development.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "high", "disease": "Skeletal anomalies", "glycan_involvement": "Proper glycosylation is required for Notch pathway function in bone development.", "mechanism": "Jagged1/Notch signaling is essential for vertebral and skeletal patterning.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "medium", "disease": "Ophthalmologic anomalies", "glycan_involvement": "Glycosylation influences Notch signaling in ocular tissue differentiation.", "mechanism": "Disrupted Notch signaling leads to anterior chamber defects (e.g., posterior embryotoxon).", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "medium", "disease": "Renal anomalies", "glycan_involvement": "Glycosylation modulates Notch signaling in kidney morphogenesis.", "mechanism": "Jagged1/Notch signaling is involved in nephron development; mutations cause renal dysplasia.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "medium", "disease": "Reproductive tract anomalies", "glycan_involvement": "Glycosylation may affect ligand-receptor interactions in reproductive tract development.", "mechanism": "Jagged1 deletion in animal models leads to ovarian and M\u00fcllerian duct anomalies.", "protein": "Jagged1", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "medium", "disease": "Hypospadias/Cryptorchidism", "glycan_involvement": "Glycosylation modulates NOTCH2 receptor function during organogenesis.", "mechanism": "NOTCH2 variants are associated with genitourinary malformations in ALGS.", "protein": "NOTCH2", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH2", "glycan_count": 9, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G47310BX", "G64527OM", "G74930WP", "G84452RH", "G43769HG", "G71142DF" ], "uniprot_id": "Q04721" }, "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "medium", "disease": "Conductive hearing loss", "glycan_involvement": "Glycosylation affects Notch pathway function in auditory system development.", "mechanism": "Jagged\u2013Notch signaling is required for inner ear bone development; mutations cause hearing loss.", "protein": "Jagged1/NOTCH2", "relationship_type": "causal", "source_pmcid": "PMC12347795" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "Contains N-glycosylation sites; glycosylation may affect protein\u2013protein interactions and exosomal trafficking.", "mechanism": "CD151 is upregulated in mosquito cells and EVs upon ZIKV infection; facilitates viral replication, transmission, and interacts directly with ZIKV NS2B and envelope proteins.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Dengue virus infection (DENV2)", "glycan_involvement": "Contains N-glycosylation sites; glycosylation may affect protein\u2013protein interactions and exosomal trafficking.", "mechanism": "CD151 is upregulated in mosquito cells and EVs upon DENV2 infection; facilitates viral replication, transmission, and interacts directly with DENV2 capsid and envelope proteins.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "N-glycosylation may regulate exosomal sorting and stability.", "mechanism": "CD151 is enriched in EVs from ZIKV-infected mosquito cells, serving as a marker for exosome-mediated viral transmission.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Dengue virus infection (DENV2)", "glycan_involvement": "N-glycosylation may regulate exosomal sorting and stability.", "mechanism": "CD151 is enriched in EVs from DENV2-infected mosquito cells, serving as a marker for exosome-mediated viral transmission.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "Glycosylation may influence antibody accessibility and function.", "mechanism": "RNAi silencing or antibody blocking of CD151 reduces ZIKV burden and infectivity in mosquito cells and EVs.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Dengue virus infection (DENV2)", "glycan_involvement": "Glycosylation may influence antibody accessibility and function.", "mechanism": "RNAi silencing or antibody blocking of CD151 reduces DENV2 burden and infectivity in mosquito cells and EVs.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347819" }, { "confidence": "medium", "disease": "Dengue virus infection", "glycan_involvement": "Tetraspanin glycoprotein; glycosylation likely involved in exosome function.", "mechanism": "Facilitates transmission of DENV via exosomes from mosquito to mammalian cells.", "protein": "Tsp29Fb", "relationship_type": "causal", "source_pmcid": "PMC12347819" }, { "confidence": "medium", "disease": "Hepatitis C virus infection", "glycan_involvement": "Tetraspanin glycoprotein; glycosylation may affect receptor function.", "mechanism": "Acts as a receptor for HCV entry into host cells.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "causal", "source_pmcid": "PMC12347819" }, { "confidence": "medium", "disease": "Human cytomegalovirus infection", "glycan_involvement": "Glycosylation may regulate membrane localization and viral entry.", "mechanism": "CD151 facilitates viral penetration in human cells.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347819" }, { "confidence": "medium", "disease": "Human papillomavirus infection", "glycan_involvement": "Glycosylation may modulate integrin interactions.", "mechanism": "CD151 drives HPV endocytosis by regulating integrin proteins.", "protein": "CD151", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12347819" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation critical for receptor function and ligand binding.", "mechanism": "Altered signaling via GPIb-IX-V complex enhances platelet activation and aggregation after prenatal THS exposure.", "protein": "Glycoprotein Ib-IX-V complex (GPIb-IX)", "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates integrin activation and fibrinogen binding.", "mechanism": "Upregulated activation leads to increased platelet aggregation and thrombogenicity.", "protein": "Integrin GPIIb-IIIa (\u03b1IIb\u03b23)", "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects collagen binding and receptor clustering.", "mechanism": "Enhanced GPVI signaling increases platelet reactivity and aggregation.", "protein": "GPVI", "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "high", "disease": "Platelet hyperactivity", "glycan_involvement": "Glycosylation regulates chemokine stability and receptor interaction.", "mechanism": "Upregulation of CXCL12 enhances collagen-induced platelet aggregation in THS-exposed mice.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Atherogenesis", "glycan_involvement": "O-glycosylation modulates filament assembly and cell signaling.", "mechanism": "Reduced miR-144 increases vimentin, promoting vascular wall changes and atherogenesis.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Platelet hyperactivity", "glycan_involvement": "Glycosylation affects enzyme localization and activity.", "mechanism": "Downregulation of miR-486-5p increases PLD1, enhancing integrin activation and granule release.", "protein": "PLD1", "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences membrane domain formation.", "mechanism": "Altered Cav1 expression modulates platelet signaling and vascular function.", "protein": "Caveolin-1 (Cav1)", "relationship_type": "biomarker", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Blood coagulation disorders", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "Altered P2Y1 expression increases platelet activation and aggregation.", "protein": "P2Y1 (P2ry1)", "protein_enriched": { "function": "Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway (PubMed:10869354, PubMed:11795891). Catalyzes the glutathione-dependent oxidoreduction of prostaglan", "gene_name": "Ptges", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9JM51" }, "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may affect PTEN stability and activity.", "mechanism": "PTEN regulates PI3K-Akt signaling, affecting platelet activation and thrombosis risk.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347917" }, { "confidence": "low", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation may regulate mitochondrial localization.", "mechanism": "Altered UCP2 expression increases oxidative stress, contributing to platelet activation.", "protein": "UCP2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O88567" }, "relationship_type": "causal", "source_pmcid": "PMC12347917" }, { "confidence": "high", "disease": "Chronic Neutrophilic Leukemia (CNL)", "glycan_involvement": "O-glycosylation at membrane-proximal domain regulates receptor dimerization; T618I impairs O-glycosylation.", "mechanism": "Activating mutations (esp. T618I) drive constitutive JAK-STAT signaling and granulocytic proliferation.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "causal", "source_pmcid": "PMC12347943" }, { "confidence": "high", "disease": "Atypical Chronic Myeloid Leukemia (aCML)", "glycan_involvement": "O-glycosylation loss at T618I site promotes ligand-independent activation.", "mechanism": "Activating mutations (T618I) lead to constitutive signaling and myeloid proliferation.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "causal", "source_pmcid": "PMC12347943" }, { "confidence": "high", "disease": "Myelodysplastic/Myeloproliferative Neoplasm-Unclassified (MDS/MPN-U)", "glycan_involvement": "O-glycosylation loss at T618I site; truncation mutations disrupt regulatory motifs.", "mechanism": "CSF3R mutations act as clonal drivers, especially T618I and truncation mutations.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12347943" }, { "confidence": "medium", "disease": "Chronic Myelomonocytic Leukemia (CMML)", "glycan_involvement": "O-glycosylation loss at T618I; truncation mutations affect receptor regulation.", "mechanism": "CSF3R mutations contribute to disease phenotype, often with co-mutations (ASXL1, TET2).", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12347943" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "O-glycosylation loss at T618I; truncation mutations prolong receptor activity.", "mechanism": "CSF3R mutations present as subclonal/secondary events, may contribute to leukemogenesis.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347943" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "O-glycosylation loss at T618I; truncation mutations disrupt regulation.", "mechanism": "Low-frequency CSF3R mutations suggest minor subclonal role.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347943" }, { "confidence": "high", "disease": "Severe Congenital Neutropenia (SCN)", "glycan_involvement": "Truncation mutations affect receptor internalization/degradation.", "mechanism": "Truncation mutations in cytoplasmic tail disrupt negative regulation, leading to neutropenia.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "causal", "source_pmcid": "PMC12347943" }, { "confidence": "low", "disease": "Myeloid Sarcoma (MS)", "glycan_involvement": "O-glycosylation loss at T618I; truncation mutations prolong signaling.", "mechanism": "CSF3R mutations detected as secondary events.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347943" }, { "confidence": "low", "disease": "Mixed Phenotype Acute Leukemia (MPAL)", "glycan_involvement": "O-glycosylation loss at T618I.", "mechanism": "CSF3R mutations present as secondary events.", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347943" }, { "confidence": "high", "disease": "Myelodysplastic/Myeloproliferative Neoplasm (general)", "glycan_involvement": "O-glycosylation loss at T618I; truncation mutations affect regulatory motifs.", "mechanism": "Constitutive activation of JAK-STAT/SRC pathways; targetable with JAK inhibitors (e.g., ruxolitinib).", "protein": "CSF3R", "protein_enriched": { "function": "Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophili", "gene_name": "CSF3R", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q99062" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347943" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Binds \u03b2-galactoside moieties on glycoproteins; enhanced binding with increased \u03b21,6-N-glycosylation during EMT.", "mechanism": "Elevated galectin-3 in RPE and chorioretinal interface; promotes EMT, proliferation, migration, and signaling (AKT/ERK/\u03b2-catenin) in RPE cells.", "protein": "Galectin-3", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Proliferative vitreoretinopathy", "glycan_involvement": "Binds glycosylated transmembrane proteins (e.g., integrins, CD147) via \u03b2-galactoside recognition.", "mechanism": "Galectin-3 promotes EMT and cell migration in RPE, contributing to fibrotic changes.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347958" }, { "confidence": "medium", "disease": "Diabetic retinopathy", "glycan_involvement": "Extracellular galectin-3 modulates glycoprotein clustering and signaling.", "mechanism": "Reduced galectin-3 expression decreases neuroinflammation and protects retinal neurons.", "protein": "Galectin-3", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12347958" }, { "confidence": "medium", "disease": "Retinal degeneration", "glycan_involvement": "Binds glycosylated proteins on RPE and microglia, affecting phagocytosis and cell survival.", "mechanism": "Galectin-3 inhibition increases photoreceptor survival after light-induced damage; but may worsen degeneration in pigment epithelium-derived factor deficiency.", "protein": "Galectin-3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12347958" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "Modulates extracellular glycoprotein interactions in retinal cells.", "mechanism": "Reduced galectin-3 expression is neuroprotective via decreased neuroinflammation.", "protein": "Galectin-3", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Subretinal fibrosis (CNV)", "glycan_involvement": "Binds glycosylated proteins involved in cell adhesion and migration.", "mechanism": "Galectin-3 inhibition reduces chorioretinal neovascularization and fibrosis.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Enhanced \u03b21,6-N-glycosylation increases galectin-3 binding during EMT.", "mechanism": "Galectin-3 promotes EMT in RPE cells, contributing to disease progression.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Proliferative vitreoretinopathy", "glycan_involvement": "Glycosylation of cell surface proteins modulates galectin-3 binding and function.", "mechanism": "Galectin-3-driven EMT and migration in RPE cells facilitate fibrotic membrane formation.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Age-related macular degeneration (AMD)", "glycan_involvement": "Reflects altered glycoprotein expression and glycosylation in disease.", "mechanism": "Increased galectin-3 detected in RPE and chorioretinal interface of AMD patients.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12347958" }, { "confidence": "medium", "disease": "Retinal degeneration", "glycan_involvement": "Modulates glycoprotein-mediated cell signaling and phagocytosis.", "mechanism": "Galectin-3 inhibition protects photoreceptors in some models, but may worsen degeneration in others.", "protein": "Galectin-3", "relationship_type": "protective/causal (context-dependent)", "source_pmcid": "PMC12347958" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Not directly discussed; glycosylation status not specified.", "mechanism": "Upregulated in PBMCs during sepsis; attenuates inflammation, tissue injury, and enhances bacterial clearance via LC3-associated phagocytosis and autophagy.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "protective", "source_pmcid": "PMC12347993" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "PEGylation (chemical modification) used to enhance stability, not glycosylation.", "mechanism": "Recombinant pro-DCD and PEGylated derivatives improve survival and reduce inflammation in murine sepsis models.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "Not specified.", "mechanism": "Circulating pro-DCD detected in patients; upregulation associated with disease state.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "Facioscapulohumeral muscular dystrophy (FSHD)", "glycan_involvement": "Not specified.", "mechanism": "Circulating pro-DCD detected in patients.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Not specified.", "mechanism": "Circulating pro-DCD detected in patients.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "Obstructive sleep apnea", "glycan_involvement": "Not specified.", "mechanism": "Circulating pro-DCD detected in patients.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Not specified.", "mechanism": "Upregulated in PBMCs in response to HIV infection.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "medium", "disease": "Myocardial ischemia/reperfusion injury", "glycan_involvement": "Not specified.", "mechanism": "Systemic administration mitigates hepatic ischemia\u2013reperfusion injury by reducing inflammatory chemokines.", "protein": "Pro-dermcidin (pro-DCD)", "protein_enriched": { "function": "Found in sweat, has an antimicrobial activity during early bacterial colonization (PubMed:11694882, PubMed:23426625). The secreted peptide assembles into homohexameric complexes that can associate wit", "gene_name": "DCD", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G49108TO" ], "uniprot_id": "P81605" }, "relationship_type": "protective", "source_pmcid": "PMC12347993" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Not specified.", "mechanism": "Antimicrobial peptide derived from pro-DCD; direct bactericidal activity against pathogens.", "protein": "Dermcidin (DCD)", "relationship_type": "protective", "source_pmcid": "PMC12347993" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Not specified.", "mechanism": "Systemic accumulation during sepsis; used as a surrogate marker.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12347993" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "COX-2 is a glycoprotein; glycosylation affects its stability and activity.", "mechanism": "Gaultherin selectively inhibits COX-2, reducing pro-inflammatory prostaglandin synthesis.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "high", "disease": "Gastric ulcer", "glycan_involvement": "COX-1 glycosylation maintains enzyme function in gastric tissue.", "mechanism": "Gaultherin spares COX-1, preventing gastric mucosal damage and ulceration.", "protein": "Cyclooxygenase-1 (COX-1)", "relationship_type": "protective", "source_pmcid": "PMC12348009" }, { "confidence": "medium", "disease": "Joint destruction", "glycan_involvement": "MMP-9 glycosylation modulates enzyme secretion and activity.", "mechanism": "Gaultherin inhibits MMP-9 secretion, reducing tissue remodeling and joint damage.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "TNF-\u03b1 glycosylation influences cytokine stability and receptor binding.", "mechanism": "Gaultherin suppresses TNF-\u03b1 release, dampening inflammatory signaling.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL-1\u03b2 glycosylation affects cytokine secretion and activity.", "mechanism": "Gaultherin inhibits IL-1\u03b2 secretion, reducing inflammation.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL-6 glycosylation modulates cytokine stability and signaling.", "mechanism": "Gaultherin downregulates IL-6, limiting inflammatory cascade.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "medium", "disease": "Muscular pain", "glycan_involvement": "IL-8 glycosylation affects chemokine activity.", "mechanism": "Gaultherin suppresses IL-8, reducing neutrophil recruitment and pain.", "protein": "Interleukin-8 (IL-8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "medium", "disease": "Joint destruction", "glycan_involvement": "ELA-2 glycosylation influences enzyme secretion.", "mechanism": "Gaultherin inhibits ELA-2, reducing tissue degradation.", "protein": "Human Neutrophil Elastase-2 (ELA-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "medium", "disease": "Oxidative stress-related diseases", "glycan_involvement": "Hyaluronidase is a glycoprotein; glycosylation affects substrate specificity.", "mechanism": "Gaultherin inhibits hyaluronidase, preserving extracellular matrix integrity.", "protein": "Hyaluronidase", "protein_enriched": { "function": "Together with its co-chaperonin GroES, plays an essential role in assisting protein folding. The GroEL-GroES system forms a nano-cage that allows encapsulation of the non-native substrate proteins and", "gene_name": "groEL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C0N7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "ATP2B2 glycosylation may affect membrane localization and function.", "mechanism": "Gaultherin binds ATP2B2, potentially modulating calcium homeostasis and synaptic signaling.", "protein": "ATP2B2 (Plasma Membrane Calcium ATPase 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348009" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Upregulation of FoxO3\u03b1 increases transcription of muscle-specific E3 ubiquitin ligases, promoting muscle protein degradation.", "protein": "FoxO3\u03b1", "protein_enriched": { "function": "Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pi", "gene_name": "FOXA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y261" }, "relationship_type": "causal", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Increased expression correlates with muscle protein degradation and sarcopenia progression.", "protein": "MAFbx/atrogin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Elevated MuRF1 promotes ubiquitin-mediated degradation of muscle proteins, contributing to sarcopenia.", "protein": "MuRF1", "relationship_type": "biomarker", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Muscle atrophy", "glycan_involvement": "Not discussed", "mechanism": "FoxO3\u03b1 activation leads to increased expression of muscle-degrading E3 ligases, causing muscle atrophy.", "protein": "FoxO3\u03b1", "protein_enriched": { "function": "Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pi", "gene_name": "FOXA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y261" }, "relationship_type": "causal", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Muscle atrophy", "glycan_involvement": "Not discussed", "mechanism": "Acts as a marker and mediator of muscle protein degradation in atrophy.", "protein": "MAFbx/atrogin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Muscle atrophy", "glycan_involvement": "Not discussed", "mechanism": "MuRF1 upregulation is associated with increased muscle protein breakdown in atrophy.", "protein": "MuRF1", "relationship_type": "biomarker", "source_pmcid": "PMC12348042" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Downregulation by beLP-K reduces E3 ligase expression and muscle degradation.", "protein": "FoxO3\u03b1", "protein_enriched": { "function": "Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pi", "gene_name": "FOXA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y261" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348042" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Inhibition by beLP-K reduces muscle protein degradation.", "protein": "MAFbx/atrogin-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348042" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "Suppression by beLP-K protects against muscle loss.", "protein": "MuRF1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348042" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Not discussed", "mechanism": "beLP-K administration decreases FoxO3\u03b1 expression, mitigating sarcopenia.", "protein": "FoxO3\u03b1", "protein_enriched": { "function": "Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pi", "gene_name": "FOXA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y261" }, "relationship_type": "protective", "source_pmcid": "PMC12348042" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects IL-6 stability and receptor binding.", "mechanism": "IL-6 is overexpressed in RA, driving inflammation; targeted by biologics (e.g., tocilizumab).", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates secretion and receptor interactions.", "mechanism": "TNF-\u03b1 is a central pro-inflammatory cytokine in RA pathogenesis; targeted by anti-TNF biologics.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "high", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "IL-1\u03b2 drives colonic inflammation; AuNPs inhibit IL-1\u03b2-induced inflammation in models.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "Glycosylation influences cytokine stability.", "mechanism": "IL-17 promotes tissue inflammation; AuNPs downregulate IL-17 in colitis models.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "high", "disease": "Collagen-induced arthritis", "glycan_involvement": "Glycosylation modulates cytokine function.", "mechanism": "IL-6 upregulated in CIA; AuNPs reduce IL-6 expression and inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "high", "disease": "Collagen-induced arthritis", "glycan_involvement": "Glycosylation affects receptor binding.", "mechanism": "TNF-\u03b1 mediates joint inflammation; AuNPs suppress TNF-\u03b1 expression.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-10 is anti-inflammatory; AuNPs increase IL-10 secretion, reducing hepatic inflammation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12348064" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "N-glycosylation critical for surface expression.", "mechanism": "CD86 upregulation marks M1 macrophage polarization; AuNPs modulate CD86 expression to reduce inflammation.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Heavily glycosylated; glycan binding mediates function.", "mechanism": "CD206 marks M2 macrophages; AuNPs upregulate CD206, promoting anti-inflammatory phenotype.", "protein": "CD206", "relationship_type": "protective", "source_pmcid": "PMC12348064" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "COX-2 upregulated in inflammation; AuNPs downregulate COX-2 expression.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348064" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding and clearance.", "mechanism": "Elevated LDL-C is a marker of dyslipidemia in estrogen deficiency; reduced by fermented S. fulvellum.", "protein": "Low-Density Lipoprotein (LDL)", "protein_enriched": { "function": "May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism", "gene_name": "APOA2", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G53434XO", "G29068FM", "G49108TO" ], "uniprot_id": "P02652" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348090" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "HDL is a glycoprotein; glycosylation modulates cholesterol efflux.", "mechanism": "HDL-C levels are reduced in estrogen deficiency; increased by S. fulvellum supplementation.", "protein": "High-Density Lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "AST is glycosylated; glycosylation may affect stability and secretion.", "mechanism": "Elevated AST indicates liver injury in estrogen deficiency; normalized by fermented S. fulvellum.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "ALT is glycosylated; glycosylation may influence activity.", "mechanism": "ALT elevation marks hepatic dysfunction; reduced by fermented S. fulvellum.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Visceral adiposity", "glycan_involvement": "O-glycosylation critical for secretion and function.", "mechanism": "Adiponectin (glycoprotein) improves insulin sensitivity and reduces adipocyte hypertrophy; fermentation may enhance its activity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Exopolysaccharides are glycan-rich microbial glycoproteins.", "mechanism": "Microbial exopolysaccharides modulate adipogenesis and inflammation, reducing obesity risk.", "protein": "Menaquinone-induced exopolysaccharides", "relationship_type": "protective", "source_pmcid": "PMC12348090" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "Potential glycosylation may affect nuclear localization and activity.", "mechanism": "PPAR\u03b3 regulates adipogenesis and lipid metabolism; fermentation-derived bioactives may modulate its activity.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348090" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Fucoidan binds to glycan moieties on cell-surface glycoproteins.", "mechanism": "Fucoidan interacts with glycoproteins involved in vascular health, reducing cardiovascular risk.", "protein": "Fucoidan-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects cytokine secretion and receptor interaction.", "mechanism": "Proinflammatory cytokines promote bone loss in estrogen deficiency; fermentation reduces their expression.", "protein": "Inflammatory cytokine glycoproteins (e.g., TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12348090" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation required for enzyme stability and function.", "mechanism": "Lipoprotein lipase regulates triglyceride clearance; fermentation may enhance its activity.", "protein": "Lipoprotein lipase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348090" }, { "confidence": "medium", "disease": "Fatty liver disease", "glycan_involvement": "FGF21 is glycosylated, which affects its stability and secretion.", "mechanism": "FGF21 upregulation promotes lipolysis and energy production, reducing hepatic fat accumulation.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12348106" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates its secretion and activity.", "mechanism": "Elevated hepatic TNF-\u03b1 indicates increased liver inflammation in ketogenic diet-fed mice.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348106" }, { "confidence": "high", "disease": "Adipose tissue inflammation", "glycan_involvement": "IL-1\u03b2 glycosylation affects its maturation and release.", "mechanism": "Lower IL-1\u03b2 in adipose tissue with ketogenic diets suggests reduced local inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348106" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "No direct glycan involvement reported for NLRP3 in this study.", "mechanism": "NLRP3 inflammasome activation contributes to liver inflammatory responses.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12348106" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TLR4 N-glycosylation is essential for its cell surface expression and function.", "mechanism": "TLR4 signaling is upregulated in liver with ketogenic diets, promoting inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12348106" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Leptin glycosylation affects its secretion and receptor binding.", "mechanism": "Leptin levels correlate with adipose tissue mass and energy balance.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348106" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may influence \u03b2-conglycinin's bioactivity and gut microbiota interactions.", "mechanism": "Soy \u03b2-conglycinin improves insulin resistance and slows renal deterioration in diabetic models.", "protein": "\u03b2-conglycinin", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13916" }, "relationship_type": "protective", "source_pmcid": "PMC12348106" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation may affect glycinin's digestibility and metabolic effects.", "mechanism": "Soy glycinin may contribute to lipid-lowering effects.", "protein": "Glycinin", "relationship_type": "protective", "source_pmcid": "PMC12348106" }, { "confidence": "medium", "disease": "Adipose tissue inflammation", "glycan_involvement": "FGF21 glycosylation enhances its stability and activity.", "mechanism": "FGF21 upregulation in adipose tissue improves energy metabolism and reduces inflammation.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12348106" }, { "confidence": "high", "disease": "Endotoxemia", "glycan_involvement": "TLR4 glycosylation is required for LPS recognition and signaling.", "mechanism": "TLR4 activation by endotoxin (LPS) drives systemic inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12348106" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "N-glycosylation changes affect Fc-mediated immune responses.", "mechanism": "Altered N-glycosylation of IgG modulates immune effector functions and is associated with autoimmune pathogenesis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348116" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycan structures on IgG influence antibody-dependent cellular cytotoxicity.", "mechanism": "Abnormal N-glycosylation patterns in IgG are linked to tumor progression and immune evasion.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348116" }, { "confidence": "medium", "disease": "Metabolic disorders", "glycan_involvement": "N-glycan composition modulates inflammation and metabolic regulation.", "mechanism": "Changes in IgG glycosylation are associated with metabolic syndrome and diabetes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348116" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycan modifications regulate pro- and anti-inflammatory IgG activity.", "mechanism": "N-glycosylation status of IgG correlates with chronic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348116" }, { "confidence": "low", "disease": "Metabolic disorders", "glycan_involvement": "No direct glycan involvement; phosphorylation is the PTM.", "mechanism": "Phosphorylation status of alpha-casein reflects metabolic activity and may indicate metabolic dysregulation.", "protein": "Alpha-casein", "protein_enriched": { "function": "Important role in the capacity of milk to transport calcium phosphate", "gene_name": "CSN1S1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02662" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348116" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "TNF glycosylation affects receptor binding and stability.", "mechanism": "TNF is a key mediator of inflammation; anti-TNF agents reduce disease activity.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation modulates TNF secretion and bioactivity.", "mechanism": "TNF drives joint inflammation; inhibition reduces symptoms.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation influences TNF receptor interactions.", "mechanism": "TNF promotes intestinal inflammation; anti-TNF therapy is effective.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "COVID-19 (Cytokine Storm/ARDS)", "glycan_involvement": "Glycosylation may affect TNF stability and immune recognition.", "mechanism": "Elevated TNF contributes to cytokine storm and organ damage; TNF inhibition may mitigate severity.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation may modulate TNF signaling in CNS.", "mechanism": "TNF levels correlate with disease activity and immune dysregulation.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "No direct glycan modification by gallic acid; TNF glycosylation may affect drug efficacy.", "mechanism": "Gallic acid inhibits TNF gene expression, suggesting anti-inflammatory potential.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "No direct glycan modification by aconitic acid; TNF glycosylation may influence response.", "mechanism": "Aconitic acid inhibits TNF gene expression, indicating possible therapeutic use.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "No direct glycan modification; TNF glycosylation relevant for function.", "mechanism": "Gallic and aconitic acids reduce TNF synthesis, potentially beneficial in IBD.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "COVID-19 (Cytokine Storm/ARDS)", "glycan_involvement": "No direct glycan modification; TNF glycosylation may affect immune response.", "mechanism": "Gallic and aconitic acids may suppress TNF-driven cytokine storm.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348193" }, { "confidence": "medium", "disease": "Psoriasis/Rheumatoid Arthritis/IBD", "glycan_involvement": "No direct glycan modification; TNF glycosylation may modulate effect.", "mechanism": "Crocetin paradoxically increases TNF gene expression, which may exacerbate inflammation.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "causal", "source_pmcid": "PMC12348193" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation (glucoside) improves bioavailability and maintains anti-inflammatory activity", "mechanism": "Inhibits MAPK and NF-\u03baB pathways, reducing inflammation", "protein": "Quercetin-3-O-glucoside", "relationship_type": "protective", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "IgA is a glycoprotein; glycosylation is essential for its function", "mechanism": "Flavonols stimulate beneficial microbiota, increasing IgA secretion, which prevents pathogen adhesion and inflammation", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Retinal vasoproliferative diseases", "glycan_involvement": "VEGF-A is a glycoprotein; glycosylation affects secretion and activity", "mechanism": "Quercetin nanoemulsions inhibit VEGF-A expression, reducing pathological angiogenesis", "protein": "VEGF-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "high", "disease": "Cancer (various), IBD, Psoriasis", "glycan_involvement": "Not specified", "mechanism": "Flavonols inhibit NF-\u03baB signaling, reducing pro-inflammatory cytokine expression and tumor progression", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD), Acute pancreatitis", "glycan_involvement": "TLR4 is a glycoprotein; glycosylation required for function", "mechanism": "Flavonols downregulate TLR4 expression, reducing inflammation", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLUT4 is a glycoprotein; glycosylation affects trafficking", "mechanism": "Flavonols promote GLUT4 translocation, improving glucose uptake", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "NLRP3 is a glycoprotein; glycosylation may regulate activity", "mechanism": "Flavonols inhibit NLRP3 inflammasome activation, reducing inflammation", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "medium", "disease": "Cancer (breast)", "glycan_involvement": "CD44 is a glycoprotein; glycosylation modulates ligand binding", "mechanism": "Fisetin nanocarriers target CD44 to enhance anti-tumor activity", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "low", "disease": "Inflammatory Bowel Disease (IBD), Intestinal barrier dysfunction", "glycan_involvement": "Desmosomal proteins are glycosylated; glycosylation critical for adhesion", "mechanism": "Flavonols enhance desmosome-mediated barrier integrity, reducing pathogen translocation", "protein": "Desmosomal proteins", "relationship_type": "protective", "source_pmcid": "PMC12348222" }, { "confidence": "low", "disease": "Type 2 Diabetes Mellitus (T2DM), Nephrotoxicity", "glycan_involvement": "Not specified", "mechanism": "Flavonols modulate PI3K signaling, improving glucose metabolism and renal protection", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348222" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "LDL particles are glycosylated; glycan structures affect receptor binding and clearance.", "mechanism": "Elevated LDL-C is a risk factor for atherosclerosis and cardiovascular disease.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates LDL receptor interactions.", "mechanism": "Obesity is associated with increased LDL-C levels.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects long-term glycemic control; elevated in diabetes.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Lipoprotein glycosylation affects lipid transport and metabolism.", "mechanism": "High total cholesterol is a risk factor for cardiovascular disease.", "protein": "TC", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of apolipoproteins modulates TG metabolism.", "mechanism": "Elevated triglycerides are a hallmark of dyslipidemia.", "protein": "TG", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation of HDL apolipoproteins affects anti-inflammatory properties.", "mechanism": "High HDL-C is protective against cardiovascular disease.", "protein": "HDL-C", "relationship_type": "protective", "source_pmcid": "PMC12348253" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "Elevated ALT is associated with hepatic steatosis in obesity.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated AST is associated with liver dysfunction in obesity.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects LDL clearance and vascular interactions.", "mechanism": "Elevated LDL-C contributes to vascular dysfunction and hypertension.", "protein": "LDL-C", "relationship_type": "causal", "source_pmcid": "PMC12348253" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycan structures influence LDL metabolism.", "mechanism": "High LDL-C is a key marker of dyslipidemia.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12348253" }, { "confidence": "high", "disease": "Non-small cell lung carcinoma", "glycan_involvement": "EGFR glycosylation modulates ligand binding and receptor stability, enhancing tumor selectivity.", "mechanism": "EGFR overexpression enables targeted uptake of ZnPc\u2013erlotinib conjugates for photodynamic therapy.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "FR is highly glycosylated, affecting cell surface localization and ligand binding.", "mechanism": "FR overexpression in ovarian cancer cells allows selective uptake of ZnPc\u2013folic acid conjugates for PDT.", "protein": "Folate Receptor (FR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "medium", "disease": "Multidrug resistant breast cancer", "glycan_involvement": "P-gp glycosylation influences membrane trafficking and drug efflux activity.", "mechanism": "ZnPc\u2013lenvatinib conjugates suppress P-gp expression, reversing MDR and enhancing PDT efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "FAP glycosylation affects enzymatic activity and tumor microenvironment localization.", "mechanism": "FAP-cleavable ZnPc\u2013doxorubicin conjugates enable tumor-specific drug release and PDT.", "protein": "Fibroblast Activation Protein (FAP)", "protein_enriched": { "function": "Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammati", "gene_name": "Fap", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G01937VC", "G49108TO" ], "uniprot_id": "P97321" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "MAO-A glycosylation may affect mitochondrial targeting and stability.", "mechanism": "MAO-A overexpression in prostate cancer enables selective uptake of ZnPc\u2013moclobemide conjugates.", "protein": "Monoamine Oxidase A (MAO-A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "TSPO glycosylation modulates mitochondrial localization.", "mechanism": "TSPO ligand\u2013ZnPc conjugates target mitochondria in cancer cells for enhanced PDT.", "protein": "Translocator Protein (TSPO)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "COX-2 glycosylation regulates enzyme activity and membrane association.", "mechanism": "ZnPc\u2013indomethacin conjugates bind COX-2, enabling targeted PDT in inflamed tissues.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "low", "disease": "Leukemia (myeloid origin)", "glycan_involvement": "EGF glycosylation affects receptor binding and cell signaling.", "mechanism": "EGF peptide-conjugated ZnPc targets EGF receptor-overexpressing leukemia cells for PDT.", "protein": "Human Epidermal Growth Factor (EGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "medium", "disease": "Multidrug resistant breast cancer", "glycan_involvement": "VEGFR glycosylation modulates ligand binding and receptor activation.", "mechanism": "ZnPc\u2013lenvatinib conjugates target VEGFR, enhancing PDT and overcoming MDR.", "protein": "Vascular Endothelial Growth Factor Receptor (VEGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "low", "disease": "Ovarian cancer", "glycan_involvement": "SMVT glycosylation affects transporter function and cell surface expression.", "mechanism": "Biotin-conjugated ZnPc exploits SMVT overexpression for targeted PDT in ovarian cancer.", "protein": "Biotin Receptor (SMVT/SLC5A6)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348348" }, { "confidence": "high", "disease": "chronic wounds", "glycan_involvement": "O-glycosylation at C-terminal domain forms 'hairy' layer for micelle stability and bioactivity.", "mechanism": "Glycosylated \u03ba-casein stabilizes micelle surface, enhances water-binding and exudate absorption, supporting wound healing.", "protein": "\u03ba-casein", "protein_enriched": { "function": "Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk", "gene_name": "CSN3", "glycan_count": 21, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G18717LR", "G29931IJ", "G45637XA", "G67200RM", "G74722FL", "G81006GJ", "G10651WD", "G31685JQ", "G70649KP", "G55507CF", "G00031MO", "G01614ZM", "G14669DU", "G46748BU", "G49108TO", "G56682BC", "G63628AV", "G64973KT", "G65562ZE", "G71549TN", "G89210OT" ], "uniprot_id": "P02668" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348495" }, { "confidence": "high", "disease": "skin infection", "glycan_involvement": "Glycosylation enhances water-binding and antimicrobial properties.", "mechanism": "Casein-based dressings show antimicrobial activity, reducing bacterial load and supporting tissue regeneration.", "protein": "casein (general)", "relationship_type": "protective", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "tissue inflammation", "glycan_involvement": "Peptide glycosylation may affect immunomodulatory activity.", "mechanism": "Immunopeptides modulate cytokine levels (TNF-\u03b1, IL-1\u03b2, IL-6), reducing inflammation and promoting healing.", "protein": "casein-derived immunopeptides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "atopic dermatitis", "glycan_involvement": "Glycosylation increases stability and bioactivity.", "mechanism": "Glycosylated casein microcapsules provide stability and support skin barrier function in atopic dermatitis.", "protein": "glycosylated casein", "relationship_type": "protective", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "HepaRG cell carcinoma", "glycan_involvement": "Glycosylation in exosomal \u03ba-casein may modulate immune and anticancer activity.", "mechanism": "Exosomal \u03ba-casein enhances anticancer effects, promoting cell death in HepaRG carcinoma cells.", "protein": "colostrum-derived exosomal \u03ba-casein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "biofilm-associated infection", "glycan_involvement": "Surface glycosylation aids in antimicrobial and anti-biofilm activity.", "mechanism": "Casein micelles disrupt biofilm formation and reduce infection risk in wounds.", "protein": "casein micelles", "relationship_type": "protective", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "oxidative stress-related skin damage", "glycan_involvement": "Glycosylation may enhance antioxidant properties.", "mechanism": "Nanocomposite hydrogels with casein and essential oils reduce oxidative stress and accelerate healing.", "protein": "casein-loaded nanocomposites", "relationship_type": "protective", "source_pmcid": "PMC12348495" }, { "confidence": "medium", "disease": "chronic wounds", "glycan_involvement": "Glycosylation may improve carrier stability and bioactivity.", "mechanism": "Casein-lipid nanocarriers promote cell viability and wound closure, supporting tissue regeneration.", "protein": "casein-lipid nanocarriers", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348495" }, { "confidence": "high", "disease": "burns", "glycan_involvement": "Glycosylation contributes to hydrogel moisture retention and healing properties.", "mechanism": "Casein-based hydrogel cream accelerates epithelisation and reduces inflammation in burn wounds.", "protein": "casein-based hydrogel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348495" }, { "confidence": "high", "disease": "milk allergy", "glycan_involvement": "Glycosylation can affect allergenicity and immune recognition.", "mechanism": "Casein is a major milk allergen, especially in children; glycosylation may influence immunogenicity.", "protein": "casein (general)", "relationship_type": "causal", "source_pmcid": "PMC12348495" }, { "confidence": "high", "disease": "Intestinal Dysfunction", "glycan_involvement": "SI is a heavily glycosylated brush border enzyme; glycosylation is essential for its stability and function.", "mechanism": "Increased SI expression correlates with improved intestinal morphology and nutrient absorption.", "protein": "Sucrase-Isomaltase (SI)", "protein_enriched": { "function": "Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides", "gene_name": "SI", "glycan_count": 5, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G28681TP", "G92050GC", "G22768VO", "G81315DD", "G49108TO" ], "uniprot_id": "P14410" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348533" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "SGLT-1 glycosylation affects membrane localization and glucose transport activity.", "mechanism": "Upregulation of SGLT-1 enhances glucose absorption; dietary intervention modulates its expression, impacting glycemic control.", "protein": "SGLT-1", "relationship_type": "biomarker", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Intestinal Dysfunction", "glycan_involvement": "PepT-1 glycosylation is required for proper folding and trafficking to the brush border.", "mechanism": "Higher PepT-1 expression improves peptide absorption and intestinal functionality.", "protein": "PepT-1", "relationship_type": "biomarker", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Intestinal Dysfunction", "glycan_involvement": "AP is N-glycosylated, which is critical for enzymatic activity and stability.", "mechanism": "AP expression correlates with amino acid absorption and enterocyte health.", "protein": "Aminopeptidase (AP)", "relationship_type": "biomarker", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation of SI is necessary for its digestive function.", "mechanism": "Enhanced SI expression after dietary intervention supports improved carbohydrate digestion, contributing to reduced adiposity.", "protein": "Sucrase-Isomaltase (SI)", "protein_enriched": { "function": "Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides", "gene_name": "SI", "glycan_count": 5, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G28681TP", "G92050GC", "G22768VO", "G81315DD", "G49108TO" ], "uniprot_id": "P14410" }, "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation regulates SGLT-1 activity and glucose uptake.", "mechanism": "Modulation of SGLT-1 expression by resistant starch/fiber intake is associated with lower body weight gain.", "protein": "SGLT-1", "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation is essential for SI function and interaction with dietary substrates.", "mechanism": "Improved SI expression is linked to better lipid profile via enhanced carbohydrate digestion and SCFA production.", "protein": "Sucrase-Isomaltase (SI)", "protein_enriched": { "function": "Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides", "gene_name": "SI", "glycan_count": 5, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G28681TP", "G92050GC", "G22768VO", "G81315DD", "G49108TO" ], "uniprot_id": "P14410" }, "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects SGLT-1-mediated glucose absorption, impacting metabolic health.", "mechanism": "Diet-induced SGLT-1 modulation reduces risk factors (glucose, lipids) for cardiovascular disease.", "protein": "SGLT-1", "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation is required for PepT-1 function.", "mechanism": "Increased PepT-1 expression supports protein absorption, contributing to satiety and reduced adiposity.", "protein": "PepT-1", "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "low", "disease": "Hyperglycemia", "glycan_involvement": "N-glycosylation is critical for AP enzymatic activity.", "mechanism": "AP activity supports amino acid absorption, indirectly influencing glucose metabolism.", "protein": "Aminopeptidase (AP)", "relationship_type": "protective", "source_pmcid": "PMC12348533" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "CD36 is a glycoprotein; glycosylation affects its localization and function in fatty acid sensing.", "mechanism": "Elevated serum CD36 is associated with newly diagnosed diabetes and insulin resistance; CD36 mediates fatty acid taste and uptake.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus", "glycan_involvement": "Glycosylation modulates CD36 receptor function in taste buds.", "mechanism": "Altered lingual CD36 expression or polymorphism may reduce fat taste sensitivity, increasing dietary fat intake and risk for GDM.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation status may affect CD36's role in fatty acid uptake and signaling.", "mechanism": "High serum CD36 correlates with insulin resistance; may mediate altered fat taste and metabolic dysregulation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "T1R2 is a glycoprotein; glycosylation is essential for receptor function.", "mechanism": "TAS1R2 polymorphisms (e.g., rs12033832) are associated with lower sweet taste sensitivity and higher sugar intake, predisposing to obesity.", "protein": "T1R2 (TAS1R2)", "protein_enriched": { "function": "Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners", "gene_name": "TAS1R2", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q8TE23" }, "relationship_type": "causal", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation affects receptor trafficking and function.", "mechanism": "Genetic variation in TAS1R2 influences sweet taste sensitivity and sugar intake, impacting diabetes risk.", "protein": "T1R2 (TAS1R2)", "protein_enriched": { "function": "Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners", "gene_name": "TAS1R2", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "Q8TE23" }, "relationship_type": "causal", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation is required for proper receptor assembly and signaling.", "mechanism": "T1R3, as part of the sweet taste receptor, regulates sweet taste and metabolic processes; altered function may affect diabetes risk.", "protein": "T1R3 (TAS1R3)", "protein_enriched": { "function": "Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate). TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners. TAS1R3 is essential ", "gene_name": "TAS1R3", "glycan_count": 4, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G13131HA", "G35029YA", "G37399XV", "G63041LO" ], "uniprot_id": "Q7RTX0" }, "relationship_type": "causal", "source_pmcid": "PMC12348552" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates CD36's function in taste and lipid metabolism.", "mechanism": "Reduced CD36-mediated fat taste sensitivity may increase fat intake, contributing to obesity.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12348552" }, { "confidence": "high", "disease": "Listeria monocytogenes infection", "glycan_involvement": "Targets peptidoglycan precursor (glycan component)", "mechanism": "Binds Lipid II, inhibits cell wall synthesis and forms pores", "protein": "Nisin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "No direct glycan modification mentioned", "mechanism": "Enhances antitumor NK and T cell responses", "protein": "Human \u03b2-defensin 2 (hBD-2)", "relationship_type": "protective", "source_pmcid": "PMC12348590" }, { "confidence": "medium", "disease": "MRSA infection", "glycan_involvement": "No direct glycan modification mentioned", "mechanism": "Enhances neutrophil response, direct antimicrobial activity", "protein": "Cathelicidin LL-37", "relationship_type": "protective", "source_pmcid": "PMC12348590" }, { "confidence": "high", "disease": "Candida albicans infection", "glycan_involvement": "Binds to glycoprotein receptor on fungal surface", "mechanism": "Binds fungal cell surface, internalized, disrupts intracellular targets", "protein": "Histatin 5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "Targets peptidoglycan precursor (glycan component)", "mechanism": "Binds Lipid II, inhibits cell wall biosynthesis", "protein": "Plectasin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "high", "disease": "Multidrug-resistant Gram-negative infections", "glycan_involvement": "Targets lipid A (glycan-lipid) of LPS", "mechanism": "Binds LPS, disrupts outer membrane", "protein": "Polymyxin B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "high", "disease": "Multidrug-resistant Gram-negative infections", "glycan_involvement": "Targets lipid A (glycan-lipid) of LPS", "mechanism": "Binds LPS, disrupts outer and cytoplasmic membranes", "protein": "Colistin (Polymyxin E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "No direct glycan modification mentioned", "mechanism": "Antitumor activity via membrane disruption", "protein": "Lycosin-I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "medium", "disease": "CRE infection", "glycan_involvement": "No direct glycan modification mentioned", "mechanism": "Forms pores in bacterial membrane, disrupts membrane potential", "protein": "Microcin E492", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "medium", "disease": "MRSA infection", "glycan_involvement": "Targets peptidoglycan precursor (glycan component)", "mechanism": "Binds Lipid II, inhibits cell wall biosynthesis", "protein": "Copsin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348590" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Asprosin is a glycoprotein hormone; glycosylation is essential for secretion and stability.", "mechanism": "Elevated circulating asprosin correlates with MASLD severity and promotes hepatic glucose production.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348634" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for hormone function.", "mechanism": "Asprosin levels increase in obesity, stimulating food intake and hepatic glucose output.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348634" }, { "confidence": "high", "disease": "T2DM", "glycan_involvement": "Glycosylation critical for activity.", "mechanism": "Elevated asprosin in T2DM patients promotes hyperglycemia via hepatic Olfr734 activation.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348634" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Olfr734 is a glycoprotein GPCR; glycosylation affects receptor trafficking and function.", "mechanism": "Hepatic Olfr734 knockdown increases liver triglycerides and worsens MASLD in DIO mice.", "protein": "Olfr734", "protein_enriched": { "function": "", "gene_name": "Ccm2l", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8VCC6" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "Olfr734 expression is upregulated in hyperglycemic states and contributes to increased hepatic glucose production.", "protein": "Olfr734", "protein_enriched": { "function": "", "gene_name": "Ccm2l", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8VCC6" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "OR4M1 is a glycoprotein GPCR; glycosylation likely affects receptor function.", "mechanism": "Hepatic OR4M1 (human Olfr734 ortholog) levels are increased in male patients with obesity and T2DM.", "protein": "OR4M1", "protein_enriched": { "function": "Odorant receptor", "gene_name": "OR1N2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NGR9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Grp78/BiP is N-glycosylated; glycosylation required for chaperone activity.", "mechanism": "Grp78/BiP downregulation (after Olfr734 knockdown) is associated with increased hepatic lipid accumulation and MASLD.", "protein": "Grp78/BiP", "relationship_type": "protective", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Olfr734 knockdown reduces Sirt1, impairing fatty acid oxidation and promoting steatosis.", "protein": "Sirt1", "relationship_type": "protective", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects GPCR function.", "mechanism": "Olfr734 knockdown increases hepatic insulin resistance and gluconeogenesis.", "protein": "Olfr734", "protein_enriched": { "function": "", "gene_name": "Ccm2l", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8VCC6" }, "relationship_type": "causal", "source_pmcid": "PMC12348634" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation likely modulates receptor function.", "mechanism": "OR4M1 knockdown in human hepatic cells increases lipid accumulation; effect reversed by Sirt1 activation.", "protein": "OR4M1", "protein_enriched": { "function": "Odorant receptor", "gene_name": "OR1N2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8NGR9" }, "relationship_type": "causal", "source_pmcid": "PMC12348634" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Mucin glycoprotein degradation by A. muciniphila; glycosylation status affects colonization.", "mechanism": "Increased abundance ameliorates diabetes via mucin degradation and gut barrier maintenance.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Altered mucin glycosylation impacts susceptibility to degradation.", "mechanism": "Excessive proliferation may disrupt mucin balance, damaging intestinal barrier and exacerbating colitis.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "causal", "source_pmcid": "PMC12348637" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Fermentation of dietary glycans (fiber, mucin O-glycans) to SCFAs.", "mechanism": "SCFA production by Clostridiales supports metabolic health and reduces obesity risk.", "protein": "Clostridiales", "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Fermentation of host and dietary glycans.", "mechanism": "SCFA production improves metabolic balance and gut health.", "protein": "Rikenellaceae", "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Degradation of complex glycans (dietary and mucin).", "mechanism": "SCFA production and glycan degradation support gut health.", "protein": "Bacteroidales", "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Utilizes dietary and host glycans for colonization.", "mechanism": "Reduced abundance in WD-induced dysbiosis; restoration improves gut health.", "protein": "Lactobacillus", "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Utilizes host-derived glycans during inflammation.", "mechanism": "Overgrowth associated with WD-induced dysbiosis and metabolic dysfunction.", "protein": "Escherichia", "relationship_type": "causal", "source_pmcid": "PMC12348637" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Fermentation of dietary and mucin glycans.", "mechanism": "SCFA production supports metabolic health.", "protein": "Ruminococcaceae", "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "low", "disease": "Dysbiosis", "glycan_involvement": "Potential utilization of host glycans.", "mechanism": "Increased abundance linked to WD-induced dysbiosis.", "protein": "Mogibacteriaceae", "relationship_type": "causal", "source_pmcid": "PMC12348637" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Mucin glycoprotein degradation; glycosylation status affects colonization and SCFA production.", "mechanism": "Increased abundance improves metabolic health and reduces obesity risk.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC12348637" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP glycosylation affects A\u03b2 production and aggregation.", "mechanism": "A\u03b2 accumulation forms plaques, disrupts neuronal communication, induces inflammation, and leads to neuronal death.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12348645" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "Tau O-glycosylation modulates aggregation propensity.", "mechanism": "Hyperphosphorylated Tau aggregates into neurofibrillary tangles, disrupting intracellular transport and causing neuronal death.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12348645" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APOE glycosylation affects lipid binding and A\u03b2 interaction.", "mechanism": "APOE \u03b54 allele increases risk of late-onset AD by influencing A\u03b2 clearance and aggregation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "risk factor/biomarker", "source_pmcid": "PMC12348645" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CD147 N-glycosylation modulates its function in A\u03b2 metabolism.", "mechanism": "Downregulation of CD147 by resveratrol reduces A\u03b2 production and secretion.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CRP glycosylation affects its inflammatory activity.", "mechanism": "Monomeric CRP promotes neuroinflammation and increases AD risk post-stroke.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12348645" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "AChE glycosylation influences enzyme stability and activity.", "mechanism": "AChE inhibition improves cholinergic signaling and mitigates AD symptoms.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "BChE glycosylation affects enzyme activity.", "mechanism": "BChE inhibition complements AChE inhibition for symptomatic AD treatment.", "protein": "Butyrylcholinesterase (BChE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "BACE1 N-glycosylation modulates its trafficking and activity.", "mechanism": "BACE1 cleaves APP to generate A\u03b2; inhibition reduces A\u03b2 production.", "protein": "Beta-secretase 1 (BACE1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "TLR4 glycosylation required for proper folding and signaling.", "mechanism": "TLR4 activation triggers neuroinflammation; resveratrol inhibits TLR4 oligomerization, reducing inflammation.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "high", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "APP N- and O-glycosylation regulate processing and A\u03b2 generation.", "mechanism": "APP processing generates A\u03b2; mutations and altered glycosylation increase pathogenic A\u03b2.", "protein": "Amyloid-beta precursor protein (APP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12348645" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "FGF19 induced by FXR inhibits CYP7A1, reducing bile acid synthesis and improving metabolic homeostasis.", "protein": "FGF19", "protein_enriched": { "function": "Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component o", "gene_name": "CWC22", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9HCG8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348650" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation essential for LDLR function and trafficking.", "mechanism": "FXR upregulates LDLR, enhancing cholesterol clearance and reducing hepatic steatosis.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "protective", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation affects chemokine stability and receptor interaction.", "mechanism": "Primary bile acids induce CXCL16 secretion, promoting NKT cell recruitment and immune activation in liver.", "protein": "CXCL16", "relationship_type": "causal", "source_pmcid": "PMC12348650" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 secretion and activity.", "mechanism": "FXR inhibits TGF-\u03b21/Smad pathway, reducing fibrogenesis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences filament assembly.", "mechanism": "FXR activation reduces \u03b1-SMA expression, indicating decreased hepatic stellate cell activation.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC12348650" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation critical for collagen fibril formation.", "mechanism": "VDR inhibits COL1A1 gene expression, blocking HSC transformation to myofibroblasts.", "protein": "COL1A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for enzyme activity and secretion.", "mechanism": "TGR5 activation upregulates PC1, increasing GLP-1 secretion and improving insulin sensitivity.", "protein": "PC1", "relationship_type": "protective", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation affects IDE stability and activity.", "mechanism": "TUDCA activates S1PR2, enhancing IDE activity and ameliorating hyperinsulinemia.", "protein": "IDE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may regulate inflammasome assembly.", "mechanism": "FXR inhibits NLRP3 inflammasome activation, reducing inflammation and fibrosis.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12348650" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation modulates chemokine secretion.", "mechanism": "TSPO ligand Atriol downregulates CXCL1, ameliorating steatosis, inflammation, and fibrosis.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348650" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "LDLR mediates cholesterol uptake; upregulation enhances LDL clearance, reducing hyperlipidemia.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348653" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation affects secretion and function.", "mechanism": "PCSK9 promotes LDLR degradation; inhibition increases LDLR levels, lowering cholesterol.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348653" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation modulates receptor stability.", "mechanism": "SRB1 mediates hepatic uptake of HDL cholesterol, promoting reverse cholesterol transport and reducing atherosclerosis risk.", "protein": "SRB1", "relationship_type": "protective", "source_pmcid": "PMC12348653" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for trafficking and function.", "mechanism": "ABCA1 promotes cholesterol efflux to HDL, reducing foam cell formation and atherosclerosis.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12348653" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "NPC1L1 mediates intestinal cholesterol absorption; inhibition reduces plasma cholesterol.", "protein": "NPC1L1", "protein_enriched": { "function": "Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant ste", "gene_name": "NPC1L1", "glycan_count": 1, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UHC9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348653" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "C-type lectin domain binds glycosylated ligands.", "mechanism": "LOX-1 mediates oxLDL uptake, promoting foam cell formation and atherosclerosis.", "protein": "LOX-1", "protein_enriched": { "function": "Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that", "gene_name": "OLR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P78380" }, "relationship_type": "causal", "source_pmcid": "PMC12348653" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Not specified.", "mechanism": "SREBP-1 upregulates genes for lipid synthesis, contributing to hyperlipidemia.", "protein": "SREBP-1", "relationship_type": "causal", "source_pmcid": "PMC12348653" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Predicted N-glycosylation may affect receptor function.", "mechanism": "AdipoR2 activation enhances fatty acid oxidation and reduces hepatic lipid accumulation.", "protein": "AdipoR2", "relationship_type": "protective", "source_pmcid": "PMC12348653" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "O-glycosylation modulates hormone stability.", "mechanism": "CCK suppresses appetite and reduces lipid intake.", "protein": "CCK", "relationship_type": "protective", "source_pmcid": "PMC12348653" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "LPL hydrolyzes triglycerides; modulation affects plasma TG levels.", "protein": "LPL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348653" }, { "confidence": "high", "disease": "Impaired bone healing", "glycan_involvement": "Glycosylation modulates VEGF stability and receptor binding.", "mechanism": "VEGF promotes angiogenesis and supports MSC differentiation for bone matrix formation.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348693" }, { "confidence": "high", "disease": "Impaired bone healing", "glycan_involvement": "Glycosylation affects FGF-2 bioactivity and ECM interactions.", "mechanism": "FGF-2 stimulates angiogenesis and osteogenesis in bone scaffolds.", "protein": "FGF-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348693" }, { "confidence": "high", "disease": "Impaired bone healing", "glycan_involvement": "Glycosylation required for BMP-2 secretion and activity.", "mechanism": "BMP-2 induces osteogenic differentiation of MSCs via TGF-\u03b2 signaling.", "protein": "BMP-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348693" }, { "confidence": "high", "disease": "Bone fracture", "glycan_involvement": "Glycosylation regulates collagen fibril formation and stability.", "mechanism": "Type I collagen forms the organic matrix for bone regeneration.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348693" }, { "confidence": "medium", "disease": "Graft-versus-host disease (GVHD)", "glycan_involvement": "Glycosylation influences CD90 cell surface expression and immune interactions.", "mechanism": "CD90 marks MSCs used in bone scaffolds; immune recognition can trigger GVHD.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348693" }, { "confidence": "medium", "disease": "Impaired bone healing", "glycan_involvement": "Glycosylation modulates CD105 function in TGF-\u03b2 signaling.", "mechanism": "CD105 marks MSCs with osteogenic potential in bone regeneration.", "protein": "CD105 (Endoglin)", "relationship_type": "biomarker", "source_pmcid": "PMC12348693" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation may affect transcriptional activity.", "mechanism": "Osterix regulates osteoblast differentiation; deficiency impairs bone formation.", "protein": "Osterix (SP7)", "relationship_type": "causal", "source_pmcid": "PMC12348693" }, { "confidence": "medium", "disease": "Bone fracture", "glycan_involvement": "Glycosylation can modulate DNA binding and stability.", "mechanism": "Runx2 is a master regulator of osteoblast differentiation and bone repair.", "protein": "Runx2", "protein_enriched": { "function": "Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). Essential for the maturation of osteoblasts and both intra", "gene_name": "RUNX2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13950" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348693" }, { "confidence": "high", "disease": "Impaired bone healing", "glycan_involvement": "Glycosylation required for TGF-\u03b2 secretion and receptor binding.", "mechanism": "TGF-\u03b2 signaling promotes MSC differentiation and bone matrix deposition.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348693" }, { "confidence": "medium", "disease": "Post-surgical infection", "glycan_involvement": "Glycosylation impacts collagen's interaction with antimicrobial agents.", "mechanism": "Collagen-based scaffolds can be functionalized to reduce infection risk.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12348693" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA glycosylation patterns (N-glycans) differ between cancer and benign conditions, improving diagnostic specificity.", "mechanism": "PSA is secreted by prostatic epithelial cells; elevated serum levels indicate malignancy.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "high", "disease": "Benign prostatic hyperplasia", "glycan_involvement": "Altered glycosylation patterns can help distinguish benign from malignant PSA.", "mechanism": "Elevated PSA can also result from benign prostatic hyperplasia, causing diagnostic overlap.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostatitis", "glycan_involvement": "Glycosylation analysis may improve specificity.", "mechanism": "Inflammation increases PSA levels, leading to false positives.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSMA is a heavily N-glycosylated transmembrane protein; glycosylation affects its stability and cell surface expression.", "mechanism": "PSMA is overexpressed in prostate cancer cells and used for imaging and targeted therapy.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "CEA is highly glycosylated; cancer-associated glycoforms are more prevalent in malignancy.", "mechanism": "CEA is included in multiplex panels to improve diagnostic specificity.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "AMACR is glycosylated; glycosylation may affect its detection and stability.", "mechanism": "AMACR is overexpressed in prostate cancer tissue and used for tumor cell labeling.", "protein": "Alpha-methylacyl-CoA racemase (AMACR)", "protein_enriched": { "function": "Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:10655068, PubMed:11060359, PubMed:7649182). Acts only on coenzyme A thioesters,", "gene_name": "AMACR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UHK6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "PSCA is GPI-anchored and glycosylated; glycosylation may influence cell surface localization.", "mechanism": "PSCA expression correlates with tumor grade and subtype.", "protein": "Prostate stem cell antigen (PSCA)", "protein_enriched": { "function": "May be involved in the regulation of cell proliferation. Has a cell-proliferation inhibition activity in vitro", "gene_name": "PSCA", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43653" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "O-glycosylation is altered in cancer, exposing novel epitopes.", "mechanism": "MUC1 is overexpressed and aberrantly glycosylated in prostate cancer, used for imaging and drug delivery.", "protein": "Mucin 1 (MUC1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12348777" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation modulates E-cadherin stability and cell adhesion.", "mechanism": "Loss of E-cadherin is associated with epithelial\u2013mesenchymal transition and metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348777" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation is critical for PSMA function and targeting.", "mechanism": "PSMA-targeted agents enable imaging and therapy of metastatic lesions.", "protein": "Prostate-specific membrane antigen (PSMA)", "protein_enriched": { "function": "Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate.", "gene_name": "FOLH1", "glycan_count": 43, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G07246CJ", "G10819WX", "G41071NU", "G49906RN", "G59626AS", "G65184UU", "G70441OD", "G80920RR", "G83646BJ", "G85282JO", "G87661QW", "G05049YU", "G06247RL", "G13131HA", "G27058EU", "G43223CG", "G49755GI", "G68490OW", "G70232NH", "G90659AW", "G92135MA", "G98611JV", "G35541EV", "G46503DX", "G50856PC", "G53075ES", "G69521XL", "G82443XX", "G31852PQ", "G41247ZX", "G42124LM", "G62765YT", "G59924QI", "G81315DD", "G92406TI", "G22768VO", "G83460ZZ", "G01650EU", "G02815KT", "G02886BB", "G28541PG", "G41840AI", "G43769HG" ], "uniprot_id": "Q04609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348777" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycation (non-enzymatic addition of glucose to N-terminal valine of hemoglobin beta chain)", "mechanism": "Reflects average blood glucose via non-enzymatic glycation of hemoglobin", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation affects serum half-life and receptor binding", "mechanism": "Transferrin saturation decreases in iron deficiency; glycosylation status may affect function", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "Glycosylation influences serum stability", "mechanism": "Low ferritin indicates depleted iron stores; glycosylation may affect stability", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "medium", "disease": "Vitamin B12 deficiency", "glycan_involvement": "N-glycosylation modulates plasma half-life", "mechanism": "Transcobalamin transports B12; deficiency impairs delivery", "protein": "Vitamin B12-binding protein (Transcobalamin)", "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "N-glycan composition modulates effector function", "mechanism": "Altered IgG glycosylation patterns reflect inflammatory status", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "medium", "disease": "Protein malnutrition", "glycan_involvement": "Glycation (non-enzymatic) can impair function", "mechanism": "Low serum albumin indicates protein deficiency; glycation increases in hyperglycemia", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation modulates plasma half-life", "mechanism": "CRP rises in inflammation; glycosylation affects clearance", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "low", "disease": "Micronutrient deficiency", "glycan_involvement": "N-glycosylation affects function and clearance", "mechanism": "Haptoglobin binds free hemoglobin; altered in hemolysis and inflammation", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation influences secretion and receptor interaction", "mechanism": "ApoB levels reflect atherogenic lipoproteins; glycosylation may affect lipid metabolism", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "low", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation modulates cell surface expression", "mechanism": "Upregulated in iron deficiency; glycosylation affects receptor stability", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12348797" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects membrane localization and stability.", "mechanism": "Digoxin (a glycoside) inhibits Na+/K+-ATPase, enhancing cardiac contractility.", "protein": "Na+/K+-ATPase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates nuclear translocation and DNA binding.", "mechanism": "Nano-phytomedicines (curcumin, resveratrol) inhibit NF-\u03baB activation, reducing tumor proliferation and inflammation.", "protein": "NF-\u03baB (p65 subunit)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation regulates PI3K stability and signaling.", "mechanism": "Nanoformulated quercetin inhibits PI3K/Akt signaling, suppressing cell proliferation.", "protein": "PI3K (p85 subunit)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation influences MAPK/ERK activation.", "mechanism": "Nano-apigenin suppresses ERK phosphorylation, inducing apoptosis in tumor cells.", "protein": "MAPK/ERK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "Glycosylation affects Nrf2 stability and nuclear translocation.", "mechanism": "Nano-resveratrol and quercetin activate Nrf2, enhancing antioxidant defenses and reducing oxidative damage.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates anti-apoptotic function.", "mechanism": "Nano-curcumin downregulates Bcl-2, promoting apoptosis in cancer cells.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects activation and substrate recognition.", "mechanism": "Nano-phytomedicines activate caspase-3, inducing apoptosis in tumor cells.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation influences enzyme activity and stability.", "mechanism": "Nano-curcumin inhibits COX-2 expression, reducing inflammatory response.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation modulates cytokine secretion and receptor binding.", "mechanism": "Nano-berberine and curcumin inhibit NLRP3 inflammasome, reducing IL-1\u03b2 secretion.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "medium", "disease": "Inflammatory bowel disease", "glycan_involvement": "Glycosylation affects TNF-\u03b1 stability and receptor interaction.", "mechanism": "Nano-EGCG and curcumin suppress TNF-\u03b1 release, alleviating inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348851" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Not specified; PNPLA3 is a glycoprotein, but glycosylation not discussed.", "mechanism": "PNPLA3 rs738409C>G polymorphism impairs lipolysis/lipogenesis, causing hepatic lipid accumulation.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12348864" }, { "confidence": "high", "disease": "MAFLD", "glycan_involvement": "Not specified; TM6SF2 is a glycoprotein, but glycosylation not discussed.", "mechanism": "TM6SF2 rs58542926E>K polymorphism alters lipid transport, increasing MAFLD risk and advanced fibrosis.", "protein": "TM6SF2", "protein_enriched": { "function": "May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin fila", "gene_name": "FAM83H", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZRV2" }, "relationship_type": "causal", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Not specified.", "mechanism": "MBOAT7 rs641738C>T polymorphism associated with MAFLD development.", "protein": "MBOAT7", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZVQ5" }, "relationship_type": "causal", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Not specified.", "mechanism": "Loss-of-function splicing variants may protect against liver damage in MAFLD.", "protein": "HSD17B13", "protein_enriched": { "function": "", "gene_name": "FAM174A", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB", "G68008QO", "G81006GJ", "G04657PL", "G08918WF", "G80920RR" ], "uniprot_id": "Q8TBP5" }, "relationship_type": "protective", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "COL6A2 is a heavily glycosylated ECM protein; glycosylation may affect biomarker properties.", "mechanism": "COL6A2 expression in adipose tissue correlates with severity of steatosis; potential serum biomarker for simple steatosis.", "protein": "COL6A2", "relationship_type": "biomarker", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "CCDC80 is secreted and glycosylated; glycosylation may affect secretion and detection.", "mechanism": "CCDC80 expression in adipose tissue correlates with NASH severity; potential serum biomarker.", "protein": "CCDC80", "relationship_type": "biomarker", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "NASH", "glycan_involvement": "SOD3 is glycosylated; glycosylation may affect stability and biomarker utility.", "mechanism": "SOD3 expression in adipose tissue correlates with NASH severity; potential serum biomarker.", "protein": "SOD3", "relationship_type": "biomarker", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "PDGF\u03b1 is glycosylated; glycosylation may modulate activity and detection.", "mechanism": "Decreased methylation of PDGF\u03b1 in serum associates with severe MAFLD.", "protein": "PDGF\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12348864" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "PPAR\u03b3 glycosylation not specified.", "mechanism": "Hypermethylation of PPAR\u03b3 promoter in serum associates with severe fibrosis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12348864" }, { "confidence": "low", "disease": "T2DM/MAFLD", "glycan_involvement": "SREBP-2 is glycosylated; glycosylation may affect activity.", "mechanism": "Matcha supplementation increases SREBP-2, indicating protection from liver damage in T2DM rats.", "protein": "SREBP-2", "relationship_type": "protective", "source_pmcid": "PMC12348864" }, { "confidence": "high", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "CRP glycosylation affects its stability and function as an inflammatory marker.", "mechanism": "CRP levels correlate with AP severity and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348896" }, { "confidence": "high", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "IL-6 glycosylation modulates secretion and receptor binding.", "mechanism": "IL-6 is elevated in AP and reflects inflammatory status.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348896" }, { "confidence": "high", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "TNF-\u03b1 glycosylation influences receptor interaction and stability.", "mechanism": "TNF-\u03b1 is increased in AP and drives inflammation.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "IgG Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IgG levels increase with glutamine supplementation, improving immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "IgM glycosylation affects complement activation.", "mechanism": "IgM levels rise with glutamine and ulinastatin therapy, enhancing immunity.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "protective", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "IgA glycosylation is critical for mucosal transport and function.", "mechanism": "IgA increases after glutamine supplementation, supporting mucosal immunity.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Glycosylation may affect GPX4 stability and activity.", "mechanism": "GPX4 prevents ferroptosis in acinar cells; glutathione depletion worsens AP.", "protein": "Glutathione peroxidase 4 (GPX4)", "protein_enriched": { "function": "Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce cholesterol hydroperoxide", "gene_name": "GPX4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P36969" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "SOD glycosylation influences enzyme activity and localization.", "mechanism": "SOD activity decreases in AP, correlating with severity and mortality.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Albumin glycosylation affects half-life and antioxidant capacity.", "mechanism": "Serum albumin decreases in AP; glutamine supplementation increases levels.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12348896" }, { "confidence": "medium", "disease": "Acute pancreatitis (AP)", "glycan_involvement": "Glycosylation is essential for ulinastatin's protease inhibitory function.", "mechanism": "Ulinastatin reduces inflammation and improves immune markers in AP.", "protein": "Ulinastatin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348896" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "COX-1 is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "COX-1 inhibition by NSAIDs reduces prostaglandin synthesis, alleviating pain and inflammation.", "protein": "COX-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348991" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "COX-2 is a glycoprotein; glycosylation modulates its enzymatic activity.", "mechanism": "COX-2 inhibition by selective NSAIDs (e.g., celecoxib) reduces inflammation and pain.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Inflammatory pain", "glycan_involvement": "NF-\u03baB pathway is regulated by glycoprotein receptors and cytokines.", "mechanism": "NF-\u03baB activation leads to increased expression of pro-inflammatory cytokines, contributing to pain.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Inflammatory pain", "glycan_involvement": "iNOS is a glycoprotein; glycosylation may affect its localization and activity.", "mechanism": "iNOS expression increases nitric oxide production, promoting inflammation and pain.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Gouty arthritis", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects secretion and receptor binding.", "mechanism": "TNF-\u03b1 is a pro-inflammatory cytokine elevated in gout, driving joint inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Gouty arthritis", "glycan_involvement": "IL-1\u03b2 glycosylation influences its stability and activity.", "mechanism": "IL-1\u03b2 mediates inflammation in gout by promoting leukocyte recruitment.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Gouty arthritis", "glycan_involvement": "IL-6 glycosylation modulates its secretion and receptor interaction.", "mechanism": "IL-6 is upregulated in gout, contributing to inflammation and pain.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "high", "disease": "Inflammatory pain", "glycan_involvement": "Glycosylation affects COX-2's localization and function.", "mechanism": "COX-2 inhibition reduces prostaglandin-mediated pain and inflammation.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348991" }, { "confidence": "high", "disease": "Inflammatory pain", "glycan_involvement": "Glycosylation modulates COX-1 stability.", "mechanism": "COX-1 inhibition by NSAIDs contributes to analgesic effects.", "protein": "COX-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12348991" }, { "confidence": "medium", "disease": "Chronic pain", "glycan_involvement": "Glycoprotein cytokines activate NF-\u03baB signaling.", "mechanism": "NF-\u03baB activation sustains chronic inflammation and pain.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12348991" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "LPS glycan moiety interacts with immune receptors.", "mechanism": "Translocation of P. gingivalis LPS increases gut inflammation via TLR4/NF-\u03baB activation, disrupts tight junctions.", "protein": "Porphyromonas gingivalis LPS", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation required for barrier function; loss promotes disease.", "mechanism": "Oral pathogens (P. gingivalis, F. nucleatum) degrade glycosylated tight junction proteins, increasing permeability and inflammation.", "protein": "Tight junction proteins (ZO-1, occludin)", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "high", "disease": "Periodontal Disease", "glycan_involvement": "Target O-glycosylated mucins and junctional proteins.", "mechanism": "Gingipains (proteases from P. gingivalis) degrade mucins and glycoproteins, promoting tissue damage.", "protein": "Gingipains", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "LPS glycan structure modulates immune activation.", "mechanism": "F. nucleatum LPS induces pro-inflammatory cytokines, promotes tumor progression and chemoresistance.", "protein": "Fusobacterium nucleatum LPS", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Periodontal Disease", "glycan_involvement": "AI-2 signaling modulates glycoprotein-rich biofilm matrix.", "mechanism": "AI-2 mediates biofilm formation and interspecies communication, facilitating dental plaque and disease.", "protein": "Autoinducer-2 (AI-2)", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "Microbial glycan metabolism regulates IAA production.", "mechanism": "IAA reduces pro-inflammatory cytokines, inhibits lipogenesis, improves glucose tolerance.", "protein": "Indole-3-acetic acid (IAA)", "relationship_type": "protective", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "Glycosylation of receptors and ligands affects signaling.", "mechanism": "FXR/TGR5 regulate glucose and lipid metabolism, modulated by glycosylated bile acids.", "protein": "Bile acid receptors (FXR, TGR5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Surface glycoproteins mediate host-microbe interactions.", "mechanism": "S. salivarius downregulates NF-\u03baB in gut epithelium, modulating inflammation.", "protein": "Streptococcus salivarius surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Cell wall glycosylation critical for immune evasion.", "mechanism": "C. albicans glycoproteins promote Th1/Th17 imbalance, exacerbating inflammation.", "protein": "Candida albicans cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12349001" }, { "confidence": "medium", "disease": "Atherosclerosis/Cardiovascular Disease", "glycan_involvement": "Enzyme glycosylation affects activity and stability.", "mechanism": "Oral Neisseria nitrate reductase promotes NO production, supporting vascular health.", "protein": "Neisseria nitrate reductase", "relationship_type": "protective", "source_pmcid": "PMC12349001" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "POMC is a glycoprotein precursor; glycosylation may affect processing/secretion.", "mechanism": "POMC+ neurons suppress feeding; loss or ablation exacerbates obesity.", "protein": "POMC", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "GLP-1 is derived from a glycoprotein precursor; glycosylation may affect stability.", "mechanism": "GLP-1 analogues (e.g., Semaglutide) reduce food intake and body weight.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349008" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "LEPR is N-glycosylated, which is essential for receptor function.", "mechanism": "Leptin receptor signaling is critical for energy homeostasis; mutations cause obesity.", "protein": "LEPR", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "INSR is heavily N-glycosylated, required for proper folding and function.", "mechanism": "Insulin receptor mediates insulin signaling; dysfunction leads to insulin resistance.", "protein": "INSR", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "TTR is a glycoprotein; glycosylation may affect hormone binding.", "mechanism": "TTR expression is upregulated in MBH of mice treated with LiPR; involved in thyroid hormone transport.", "protein": "TTR", "relationship_type": "biomarker", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "CCKAR is N-glycosylated, important for cell surface expression.", "mechanism": "CCKAR mediates satiety signaling; reduced expression may impair appetite suppression.", "protein": "CCKAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "NPY is a glycoprotein precursor; glycosylation may affect secretion.", "mechanism": "NPY+ neurons stimulate feeding; overactivity promotes obesity.", "protein": "NPY", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "AgRP is a glycoprotein precursor; glycosylation may affect function.", "mechanism": "AgRP+ neurons stimulate feeding; increased activity linked to obesity.", "protein": "AgRP", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "CARTPT is a glycoprotein precursor; glycosylation may affect processing.", "mechanism": "CARTPT is anorexigenic; reduced expression may contribute to obesity.", "protein": "CARTPT", "relationship_type": "protective", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "MC3R is N-glycosylated, required for receptor function.", "mechanism": "MC3R mediates melanocortin signaling; dysfunction can affect energy balance.", "protein": "MC3R", "relationship_type": "causal", "source_pmcid": "PMC12349008" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (in Xeroderma pigmentosum)", "glycan_involvement": "NKp65 is N-glycosylated; glycosylation not directly linked to protection but may affect surface expression.", "mechanism": "NKp65-KACL axis restricts carcinoma invasion via skin immunosurveillance by ILC3.", "protein": "NKp65 (KLRF2)", "relationship_type": "protective", "source_pmcid": "PMC12349009" }, { "confidence": "low", "disease": "Psoriatic disease", "glycan_involvement": "N-glycosylation at stalk region (Val/Ile68) not directly linked to disease, but may modulate protein abundance.", "mechanism": "Polymorphism rs576601 (Thr131) reduces NKp65 surface expression and cytotoxicity, possibly impairing skin immunosurveillance.", "protein": "NKp65 (KLRF2)", "relationship_type": "causal (potential)", "source_pmcid": "PMC12349009" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (in Xeroderma pigmentosum)", "glycan_involvement": "Glycosylation not directly targeted, but may affect receptor function.", "mechanism": "NKp65-KACL interaction mediates cytotoxicity against KACL+ tumor cells; enhancing NKp65 function may restrict tumor invasion.", "protein": "NKp65 (KLRF2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349009" }, { "confidence": "low", "disease": "Squamous cell carcinoma (in Xeroderma pigmentosum)", "glycan_involvement": "Surface expression affected by glycosylation and polymorphism.", "mechanism": "NKp65 expression on ILC3 may indicate effective skin immunosurveillance.", "protein": "NKp65 (KLRF2)", "relationship_type": "biomarker", "source_pmcid": "PMC12349009" }, { "confidence": "low", "disease": "Squamous cell carcinoma (in Xeroderma pigmentosum)", "glycan_involvement": "Not specified.", "mechanism": "KACL expression on keratinocytes marks target cells for NKp65-mediated cytotoxicity.", "protein": "KACL (CLEC2A)", "protein_enriched": { "function": "Lectin-type cell surface receptor which may play a role in antigen capturing by dendritic cells (PubMed:11748283, PubMed:21880719, PubMed:25995448). Specifically recognizes non-sialylated galactose-te", "gene_name": "CLEC4C", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q8WTT0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349009" }, { "confidence": "low", "disease": "Psoriatic disease", "glycan_involvement": "Glycosylation status may affect NKp65 detection.", "mechanism": "NKp65 polymorphism may correlate with altered skin immune responses.", "protein": "NKp65 (KLRF2)", "relationship_type": "biomarker (potential)", "source_pmcid": "PMC12349009" }, { "confidence": "high", "disease": "Hepatitis A", "glycan_involvement": "IgM is a heavily glycosylated antibody; glycosylation is essential for its stability and immune function.", "mechanism": "Anti-HAV IgM is produced in response to HAV infection and is used for laboratory confirmation of acute hepatitis A.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349081" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Glycosylation of IgM affects its serum half-life and immune complex formation.", "mechanism": "Presence of anti-HAV IgM can help distinguish HAV-induced fulminant hepatic failure from other causes.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349081" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "LBP is N-glycosylated, which affects its stability and LPS binding.", "mechanism": "LBP levels increase with gut-derived LPS translocation due to intestinal permeability, reflecting metabolic endotoxemia in obesity.", "protein": "LPS-binding protein (LBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "sCD14 is N-glycosylated, modulating its immune signaling.", "mechanism": "sCD14 is released in response to LPS and elevated in states of increased intestinal permeability and inflammation in obesity.", "protein": "soluble CD14 (sCD14)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "IFABP glycosylation may affect its release and detection.", "mechanism": "IFABP is released into circulation upon enterocyte damage, indicating compromised intestinal barrier.", "protein": "intestinal fatty acid binding protein (IFABP)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "high", "disease": "Low-grade inflammation", "glycan_involvement": "CRP is N-glycosylated, influencing its immune effector functions.", "mechanism": "CRP is upregulated in response to systemic inflammation driven by gut-derived LPS in metabolic disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects LBP's interaction with LPS and immune receptors.", "mechanism": "LBP mediates LPS-induced inflammation, contributing to cardiovascular risk.", "protein": "LPS-binding protein (LBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates sCD14's immune signaling.", "mechanism": "Elevated sCD14 reflects chronic immune activation linked to cardiovascular risk.", "protein": "soluble CD14 (sCD14)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation affects CRP's ligand binding and clearance.", "mechanism": "CRP is a marker of systemic inflammation and predicts cardiovascular events.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "TNF\u03b1 glycosylation influences its secretion and receptor binding.", "mechanism": "TNF\u03b1 is elevated in obesity due to chronic low-grade inflammation from gut-derived LPS.", "protein": "Tumor necrosis factor alpha (TNF\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "IL-6 glycosylation modulates its stability and activity.", "mechanism": "IL-6 is upregulated in obesity-associated inflammation, partly driven by increased intestinal permeability.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "N-glycosylation affects LBP's function in LPS recognition.", "mechanism": "LBP is elevated in type 2 diabetes due to increased gut permeability and metabolic endotoxemia.", "protein": "LPS-binding protein (LBP)", "relationship_type": "biomarker", "source_pmcid": "PMC12349125" }, { "confidence": "high", "disease": "Wound healing (chronic wounds, diabetic ulcers)", "glycan_involvement": "Glycosylation affects fibrinogen's solubility and polymerization.", "mechanism": "Fibrinogen is converted to fibrin, forming hydrogels that act as provisional ECM scaffolds to promote cell migration and tissue regeneration.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "high", "disease": "Cartilage defects (osteoarthritis)", "glycan_involvement": "Glycosylation modulates collagen fibril formation and cell interactions.", "mechanism": "Collagen-based hydrogels mimic ECM, supporting chondrocyte growth and cartilage regeneration.", "protein": "Collagen (Type I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Vascular graft failure", "glycan_involvement": "Glycosylation influences elastin crosslinking and degradation.", "mechanism": "Elastin hydrogels provide elasticity and compliance, reducing intimal hyperplasia and improving graft patency.", "protein": "Elastin", "protein_enriched": { "function": "Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial ", "gene_name": "ELN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P15502" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "high", "disease": "Dry eye syndrome", "glycan_involvement": "HA is a glycosaminoglycan; its sulfation and chain length affect bioactivity.", "mechanism": "HA-based hydrogels retain moisture and support epithelial healing in ocular surfaces.", "protein": "Hyaluronic Acid (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Wound healing (chronic wounds, diabetic ulcers)", "glycan_involvement": "Retains glycosylation motifs from collagen, influencing cell adhesion.", "mechanism": "Gelatin hydrogels provide a moist environment and support cell migration for tissue repair.", "protein": "Gelatin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "VEGF glycosylation affects receptor binding and stability.", "mechanism": "Fibrin hydrogels encapsulate and release VEGF, promoting angiogenesis and cardiac tissue regeneration.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Stroke recovery", "glycan_involvement": "Glycosylation modulates fibrin network formation and degradation.", "mechanism": "Fibrin hydrogels serve as scaffolds for neural stem cell delivery and tissue repair.", "protein": "Fibrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Cancer (tumor microenvironment)", "glycan_involvement": "Glycosylation regulates fibronectin-cell interactions.", "mechanism": "Fibronectin-rich hydrogels mimic tumor ECM, supporting cancer cell invasion and drug testing.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349326" }, { "confidence": "low", "disease": "Basal cell carcinoma", "glycan_involvement": "Thrombin glycosylation affects activation and substrate specificity.", "mechanism": "Thrombin-activated hydrogels enable localized drug delivery for tumor treatment.", "protein": "Thrombin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349326" }, { "confidence": "medium", "disease": "Wound healing (chronic wounds, diabetic ulcers)", "glycan_involvement": "Glycosylation modulates plasmin activity and stability.", "mechanism": "Plasmin degrades fibrin hydrogels, regulating scaffold persistence and tissue remodeling.", "protein": "Plasmin", "protein_enriched": { "function": "Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ov", "gene_name": "PLG", "glycan_count": 67, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G33791AF", "G48414YA", "G52527GH", "G57321FI", "G53434XO", "G43417UB", "G01614ZM", "G29068FM", "G65562ZE", "G74722FL", "G00912UN", "G06356OH", "G11041DA", "G22310AV", "G36191CD", "G50045TK", "G56749GV", "G59626AS", "G84452RH", "G84467IZ", "G91365ZQ", "G02684WR", "G17015OC", "G23729WG", "G27391WQ", "G58001LT", "G81006GJ", "G82463GQ", "G00776MW", "G03706EO", "G04689DA", "G05724UK", "G06110VR", "G11346GZ", "G12793SR", "G14669DU", "G15956KF", "G20367UY", "G20425TQ", "G22768VO", "G23863VK", "G29857RC", "G39188ZX", "G42039DE", "G47012YE", "G47518TP", "G49108TO", "G49874UX", "G55220VL", "G55661CO", "G56014GC", "G60230HH", "G60452UF", "G66088HZ", "G66538GV", "G70101JE", "G74724QE", "G76675AB", "G78059CC", "G80858MF", "G82348BZ", "G85839YN", "G89186VO", "G90983OS", "G92089QC", "G93656SY", "G96622LK" ], "uniprot_id": "P00747" }, "relationship_type": "causal", "source_pmcid": "PMC12349326" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AChE is a glycoprotein; glycosylation affects its stability and function, possibly influencing inhibitor binding.", "mechanism": "Inhibition of AChE by I. obliquus extracts and encapsulated systems reduces acetylcholine breakdown, potentially improving cholinergic signaling in Alzheimer's.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349574" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "\u03b2-glucan side chains are essential for immune recognition and antitumor activity.", "mechanism": "\u03b2-glucan glycoproteins exhibit immunomodulatory and cytotoxic effects against cancer cell lines (MCF-7, HCT116, HeLa).", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation patterns modulate immune activation and direct antimicrobial effects.", "mechanism": "Glycoproteins contribute to antimicrobial activity against S. aureus, B. cereus, P. aeruginosa, and E. coli.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "\u03b2-glucan structure is critical for metabolic effects.", "mechanism": "Traditional use and literature suggest \u03b2-glucan glycoproteins improve glucose metabolism and insulin sensitivity.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycan moieties interact with immune receptors (e.g., Dectin-1).", "mechanism": "Immunomodulatory glycoproteins reduce inflammation via cytokine modulation.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "low", "disease": "Gastrointestinal disorders", "glycan_involvement": "Glycosylation mediates prebiotic and mucosal effects.", "mechanism": "Glycoproteins may support gut health and barrier function.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect inhibitor sensitivity.", "mechanism": "AChE inhibition may contribute to antiproliferative effects in cancer cells.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349574" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycan structure enhances cellular uptake and immune activation.", "mechanism": "Encapsulated glycoproteins (MIO\u2013AgNPs) show enhanced cytotoxicity against cancer cell lines.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349574" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation may facilitate AgNP binding and delivery.", "mechanism": "Synergistic action with AgNPs enhances antimicrobial efficacy.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349574" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycan moieties modulate bioactivity and blood-brain barrier interaction.", "mechanism": "Antioxidant and anti-AChE activities may protect against neurodegeneration.", "protein": "\u03b2-glucan-containing glycoproteins (from Inonotus obliquus)", "relationship_type": "protective", "source_pmcid": "PMC12349574" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Carbohydrate recognition domain mediates glycan binding, affecting signaling.", "mechanism": "Galectin-3 levels are higher in T2DM; overexpression inhibits insulin signaling and glucose uptake.", "protein": "Galectin-3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12349726" }, { "confidence": "high", "disease": "Insulin Resistance", "glycan_involvement": "Binds glycans on cell surface receptors, modulating signaling.", "mechanism": "Overexpression in skeletal muscle inhibits insulin signaling and glucose uptake.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Binds parasite and host glycans, possibly modulating immune response.", "mechanism": "Galectin-3 levels are elevated in malaria patients irrespective of diabetes status.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Cerebral Malaria", "glycan_involvement": "Carbohydrate recognition domain may interact with parasite/host glycans.", "mechanism": "Galectin-3 facilitates cerebral malaria in mice; deficiency is protective.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Mediates cell-matrix interactions via glycan binding.", "mechanism": "Involved in fibrotic processes (literature cited).", "protein": "Galectin-3", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Binds immune cell glycans, modulating inflammation.", "mechanism": "Associated with inflammation in rheumatoid arthritis.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Binds glycans on immune cells.", "mechanism": "Involved in inflammatory processes in asthma.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Certain Cancers", "glycan_involvement": "Mediates cell adhesion and migration via glycan binding.", "mechanism": "Implicated in cancer progression (literature cited).", "protein": "Galectin-3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Binds glycans in cardiac tissue.", "mechanism": "Elevated in heart failure; used as a biomarker.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Binds host and parasite glycans.", "mechanism": "Circulating galectin-9 reflects malaria severity in humans.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349726" }, { "confidence": "high", "disease": "Liver damage/metabolic syndrome", "glycan_involvement": "Glycosylation affects ALP stability and activity; changes in glycosylation may modulate enzyme function.", "mechanism": "Elevated ALP activity indicates liver dysfunction; PMK administration reduces ALP, reflecting improved liver health.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "high", "disease": "Liver damage/metabolic syndrome", "glycan_involvement": "Glycosylation regulates AST secretion and activity.", "mechanism": "High AST is a marker of liver injury; PMK lowers AST, suggesting hepatoprotective effects.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "high", "disease": "Liver damage/metabolic syndrome", "glycan_involvement": "Glycosylation influences ALT stability and serum levels.", "mechanism": "ALT elevation signals liver damage; PMK reduces ALT, indicating improved liver function.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Glycosylation modulates hemoglobin function and erythrocyte lifespan.", "mechanism": "Increased HGB correlates with improved aerobic metabolism and immune status after PMK supplementation.", "protein": "Hemoglobin (HGB)", "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Platelet glycoproteins are heavily glycosylated, affecting aggregation and immune signaling.", "mechanism": "Elevated PLT counts after PMK indicate enhanced clotting and immune function.", "protein": "Platelet glycoproteins (PLT)", "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "medium", "disease": "Pigment loss/skin pattern disorder", "glycan_involvement": "N-glycosylation is essential for tyrosinase folding and activity.", "mechanism": "PMK flavonoids enhance tyrosinase activity, promoting melanin synthesis and reticulate skin pattern.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12349994" }, { "confidence": "medium", "disease": "Acute stress/hyperglycemia", "glycan_involvement": "Glycosylation modulates ALP activity under stress conditions.", "mechanism": "Reduced ALP after PMK administration correlates with lower stress and improved metabolic status.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "medium", "disease": "Pigment loss/skin pattern disorder", "glycan_involvement": "Proper glycosylation required for tyrosinase function in melanogenesis.", "mechanism": "Flavonoids in PMK act as melanogenic agents, protecting against pigment loss.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "protective", "source_pmcid": "PMC12349994" }, { "confidence": "low", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation affects PLT-mediated immune responses.", "mechanism": "Enhanced PLT counts may contribute to immune defense against pathogens, supported by PMK antimicrobial activity.", "protein": "Platelet glycoproteins (PLT)", "relationship_type": "protective", "source_pmcid": "PMC12349994" }, { "confidence": "low", "disease": "Acute stress/hyperglycemia", "glycan_involvement": "Glycosylation influences hemoglobin function under stress.", "mechanism": "Higher HGB after PMK correlates with reduced stress and better oxygenation.", "protein": "Hemoglobin (HGB)", "relationship_type": "biomarker", "source_pmcid": "PMC12349994" }, { "confidence": "high", "disease": "Ischemic cardiomyopathy", "glycan_involvement": "GDF15 is a secreted glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "GDF15 attenuates hypoxic injury by suppressing BNIP3-mediated pathological mitophagy, preserving mitochondrial function and energy homeostasis.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Myocardial hypoxic injury", "glycan_involvement": "Glycosylation may regulate GDF15's extracellular activity.", "mechanism": "GDF15 overexpression reduces oxidative stress, maintains mitochondrial morphology, and inhibits cell death under hypoxia.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "protective", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may influence detection and stability in serum.", "mechanism": "GDF15 levels rapidly increase after myocardial injury, serving as a stress biomarker.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Pathological mitophagy", "glycan_involvement": "BNIP3 is a transmembrane glycoprotein; glycosylation may affect localization and function.", "mechanism": "BNIP3 overactivation drives excessive mitophagy, leading to mitochondrial loss and cell death in sustained hypoxia.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal", "source_pmcid": "PMC12350453" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Glycosylation may modulate GDF15's stability and signaling.", "mechanism": "GDF15 expression is associated with longevity pathways and may serve as an aging biomarker.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation may affect BNIP3's membrane integration and activity.", "mechanism": "BNIP3 induces mitochondrial depolarization and dysfunction under hypoxic stress.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Oxidative stress injury", "glycan_involvement": "Glycosylation may influence GDF15's antioxidant signaling.", "mechanism": "GDF15 reduces ROS and MDA levels, increases SOD activity, and protects cells from oxidative damage.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "protective", "source_pmcid": "PMC12350453" }, { "confidence": "medium", "disease": "Lysosomal dysfunction", "glycan_involvement": "Glycosylation may affect BNIP3's interaction with lysosomal machinery.", "mechanism": "BNIP3 overexpression impairs lysosomal acidification and autophagic flux.", "protein": "BNIP3", "protein_enriched": { "function": "Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitoch", "gene_name": "BNIP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q12983" }, "relationship_type": "causal", "source_pmcid": "PMC12350453" }, { "confidence": "medium", "disease": "Autophagy-related injury", "glycan_involvement": "Possible glycosylation may regulate LC3B's autophagic activity.", "mechanism": "LC3B-II levels increase with BNIP3-driven mitophagy, marking autophagosome formation in hypoxic injury.", "protein": "LC3B", "protein_enriched": { "function": "Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes) (PubMed:20418806, PubMed:23209295, PubMed:28017329). Plays a role in mitophagy which contributes to regulate m", "gene_name": "MAP1LC3B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9GZQ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350453" }, { "confidence": "medium", "disease": "Autophagy-related injury", "glycan_involvement": "Possible glycosylation may affect p62's adaptor function.", "mechanism": "p62 accumulates with impaired autophagic flux, indicating autophagy dysfunction in hypoxic cardiomyocytes.", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350453" }, { "confidence": "high", "disease": "Reactive retinal gliosis", "glycan_involvement": "GFAP is a glycoprotein; glycosylation may affect filament assembly and stability.", "mechanism": "Upregulation in M\u00fcller cells indicates glial activation in response to neuronal damage.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Retinal neuronal degeneration", "glycan_involvement": "GS is glycosylated; glycosylation may regulate enzyme activity and localization.", "mechanism": "Transient increase then decrease in GS-positive M\u00fcller cells reflects glial response and loss of glutamate regulation.", "protein": "GS", "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Retinal ganglion cell apoptosis", "glycan_involvement": "BRN3A is glycosylated; glycosylation may affect nuclear localization and transcriptional activity.", "mechanism": "Decreased BRN3A expression marks RGC stress and degeneration.", "protein": "BRN3A", "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "medium", "disease": "Retinal neuronal degeneration", "glycan_involvement": "Tubulin glycosylation can affect microtubule stability.", "mechanism": "Loss of \u03b2III-tubulin-positive neurons indicates progressive neuronal loss.", "protein": "\u03b2III-tubulin", "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Reactive retinal gliosis", "glycan_involvement": "Iba1 is glycosylated; glycosylation may modulate microglial activation.", "mechanism": "Increased and morphologically activated Iba1-positive microglia/macrophages reflect immune response to neuronal damage.", "protein": "Iba1", "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Retinal ganglion cell apoptosis", "glycan_involvement": "Caspase-3 glycosylation may regulate activation and apoptosis signaling.", "mechanism": "Cleaved caspase-3 marks apoptotic RGCs in advanced disease.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "GM1-gangliosidosis", "glycan_involvement": "GLB1 is a glycoprotein; glycosylation is essential for lysosomal targeting and activity.", "mechanism": "GLB1 deficiency leads to GM1 ganglioside accumulation, causing lysosomal dysfunction and neuronal degeneration.", "protein": "GLB1 (\u03b2-galactosidase)", "relationship_type": "causal", "source_pmcid": "PMC12350627" }, { "confidence": "medium", "disease": "Retinal neuronal degeneration", "glycan_involvement": "Glycosylation may affect GFAP filament dynamics and glial reactivity.", "mechanism": "GFAP upregulation in M\u00fcller cells may be targeted to modulate gliosis and neurotoxicity.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350627" }, { "confidence": "medium", "disease": "Reactive retinal gliosis", "glycan_involvement": "Glycosylation may regulate GS activity and glial metabolism.", "mechanism": "GS dysregulation in M\u00fcller cells may be targeted to restore glutamate homeostasis.", "protein": "GS", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Retinal neuronal degeneration", "glycan_involvement": "GLB1 glycosylation is required for proper lysosomal function.", "mechanism": "GLB1 loss causes GM1 ganglioside buildup in neurons, leading to apoptosis and degeneration.", "protein": "GLB1 (\u03b2-galactosidase)", "relationship_type": "causal", "source_pmcid": "PMC12350627" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Not discussed", "mechanism": "NCOA4 mediates ferritinophagy, increasing free iron and promoting ferroptosis in hepatocytes, contributing to ALF progression.", "protein": "NCOA4", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "high", "disease": "HBV-associated Acute-on-Chronic Liver Failure (HBV-ACLF)", "glycan_involvement": "Not discussed", "mechanism": "NCOA4 expression is significantly elevated in HBV-ACLF liver tissue compared to CHB and controls.", "protein": "NCOA4", "relationship_type": "biomarker", "source_pmcid": "PMC12350633" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Not discussed", "mechanism": "HNF4A transcriptionally represses NCOA4, reducing ferritinophagy and ferroptosis, thus protecting hepatocytes in ALF.", "protein": "HNF4A", "relationship_type": "protective", "source_pmcid": "PMC12350633" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Not discussed", "mechanism": "GPX4 reduces lipid peroxides, preventing ferroptosis; its expression is decreased in ALF.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12350633" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "Not discussed", "mechanism": "SLC7A11 supports GSH synthesis, counteracting ferroptosis; its expression is decreased in ALF.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12350633" }, { "confidence": "medium", "disease": "Hemochromatosis", "glycan_involvement": "TFR1 is a glycoprotein; glycosylation is important for its stability and function.", "mechanism": "TFR1 mediates iron uptake; excessive iron via TFR1 contributes to ferroptosis and liver injury in hemochromatosis.", "protein": "Transferrin receptor 1 (TFR1)", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "medium", "disease": "Alcohol-related liver disease", "glycan_involvement": "Not discussed", "mechanism": "Alcohol-induced ROS increases NCOA4-mediated ferritinophagy, promoting ferroptosis.", "protein": "NCOA4", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "Not discussed", "mechanism": "NCOA4-mediated ferritinophagy increases iron-induced oxidative stress and ferroptosis in NASH.", "protein": "NCOA4", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "low", "disease": "Wilson\u2019s disease", "glycan_involvement": "Not discussed", "mechanism": "Disrupted copper metabolism affects iron homeostasis, with NCOA4-mediated ferritinophagy contributing to ferroptosis.", "protein": "NCOA4", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "medium", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "TFR1 glycosylation may affect iron uptake efficiency.", "mechanism": "TFR1-mediated iron uptake increases intracellular iron, promoting ferroptosis in ALF.", "protein": "Transferrin receptor 1 (TFR1)", "relationship_type": "causal", "source_pmcid": "PMC12350633" }, { "confidence": "high", "disease": "Oral mucosal protection", "glycan_involvement": "O-glycosylation creates hydrated, protective barrier.", "mechanism": "Mucin coats and protects oral mucosa, preventing mechanical and chemical damage.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC12350710" }, { "confidence": "high", "disease": "Oral dryness (xerostomia)", "glycan_involvement": "Loss of glycosylation reduces mucin's water-retaining capacity.", "mechanism": "Reduced mucin levels correlate with oral dryness and impaired lubrication.", "protein": "Mucin", "relationship_type": "biomarker", "source_pmcid": "PMC12350710" }, { "confidence": "high", "disease": "Altered flavor perception", "glycan_involvement": "Glycosylation influences mucin's interaction with flavor molecules.", "mechanism": "Mucin modulates protein-flavor binding, affecting aroma release and sensory perception.", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC12350710" }, { "confidence": "medium", "disease": "Oral infection", "glycan_involvement": "Glycosylation affects lactoferrin's binding to mucin and pathogens.", "mechanism": "Lactoferrin interacts with mucin to enhance antimicrobial barrier in saliva.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "protective", "source_pmcid": "PMC12350710" }, { "confidence": "medium", "disease": "Altered flavor perception", "glycan_involvement": "Glycosylation modulates BLG's interaction with mucin.", "mechanism": "BLG-mucin interaction changes mucin conformation, affecting flavor binding.", "protein": "\u03b2-Lactoglobulin (BLG)", "protein_enriched": { "function": "Primary component of whey, it binds retinol and is probably involved in the transport of that molecule", "gene_name": "LGB", "glycan_count": 8, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G08436QU", "G36258ZR", "G49108TO", "G70101JE", "G72057XQ", "G73716BT", "G97455PT", "G99629OK" ], "uniprot_id": "P02754" }, "relationship_type": "causal", "source_pmcid": "PMC12350710" }, { "confidence": "low", "disease": "Food allergy", "glycan_involvement": "O-glycans shield protein surfaces.", "mechanism": "Mucin may mask allergenic protein epitopes, reducing immune 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"PMC12350710" }, { "confidence": "low", "disease": "Altered flavor perception", "glycan_involvement": "Glycosylation affects binding affinity.", "mechanism": "Proline-rich proteins bind flavors, modulating taste perception.", "protein": "Proline-rich proteins", "relationship_type": "causal", "source_pmcid": "PMC12350710" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "PD-L1 is glycosylated, which stabilizes its expression and function on tumor cells.", "mechanism": "PD-L1 inhibits effector T cell function via PD-1; shRNA knockdown in CARG-2020 enhances anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). 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As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "IL-12 is glycosylated for secretion and stability.", "mechanism": "IL-12 delivered by CARG-2020 activates Th1 immunity and CD8+ T cell infiltration, leading to tumor regression.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "Glycosylation required for IL-12 secretion and bioactivity.", "mechanism": "IL-12 payload in CARG-2020 induces Th1 response and cytotoxic T cell activation, promoting tumor clearance.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation essential for IL-12 function.", "mechanism": "IL-12 stimulates Th1 immunity and CD8+ T cell activation, leading to tumor regression.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "IL-17RA is glycosylated, affecting ligand binding and signaling.", "mechanism": "Extracellular domain of IL-17RA antagonizes IL-17 signaling, reducing tumor-promoting inflammation and permitting CD8+ T cell influx.", "protein": "IL-17RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "IL-17RA antagonist blocks IL-17-driven inflammation and cancer progression.", "protein": "IL-17RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect receptor-ligand interactions.", "mechanism": "IL-17RA antagonist in CARG-2020 blocks IL-17-mediated suppression of CD8+ T cell infiltration.", "protein": "IL-17RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350727" }, { "confidence": "medium", "disease": "Cancer (general, including melanoma, TNBC, CRC)", "glycan_involvement": "VSV-G is glycosylated, which affects tropism and immune recognition.", "mechanism": "VSV-G glycoprotein mediates viral entry into tumor cells, enabling delivery of immunomodulatory payloads.", "protein": "VSV-G", "protein_enriched": { "function": "Attaches the virus to host LDL receptors, inducing clathrin-dependent endocytosis of the virion (PubMed:20941355, PubMed:23589850). In the endosome, the acidic pH induces conformational changes in the", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03522" }, "relationship_type": "therapeutic_delivery_vehicle", "source_pmcid": "PMC12350727" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Mucin domain is heavily O-glycosylated, affecting immune interactions and protein stability.", "mechanism": "Downregulated in PHC tumor tissues; upregulated in circulating intermediate monocytes; correlates with disease progression and immune infiltration.", "protein": "TIM-4/TIMD4", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Soluble form retains glycosylated mucin domain, influencing detection and immune modulation.", "mechanism": "Elevated plasma sTIM-4 levels in PHC patients; improves diagnostic sensitivity when combined with AFP.", "protein": "sTIM-4 (soluble TIM-4)", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "medium", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions and immune cell recruitment.", "mechanism": "Regulates monocyte/macrophage polarization and immune microenvironment; potential target for immunotherapy.", "protein": "TIM-4/TIMD4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350753" }, { "confidence": "medium", "disease": "Chronic hepatitis B virus (HBV) infection", "glycan_involvement": "Glycosylation affects immune recognition and inflammatory signaling.", "mechanism": "Elevated TIM-4 expression in intermediate monocytes and plasma sTIM-4 in HBV-infected individuals; associated with inflammation.", "protein": "TIM-4/TIMD4", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "medium", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Glycosylation may influence anti-tumor immune responses.", "mechanism": "Higher TIM-4 expression in tumor tissue correlates with improved overall survival.", "protein": "TIM-4/TIMD4", "relationship_type": "protective", "source_pmcid": "PMC12350753" }, { "confidence": "medium", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "O-glycosylation in mucin domain modulates cytokine interactions.", "mechanism": "TIM-4+ intermediate monocytes promote tumor progression via pro-inflammatory cytokine secretion and angiogenesis.", "protein": "TIM-4/TIMD4", "relationship_type": "causal", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Glycosylation affects protein stability and immune cell signaling.", "mechanism": "TIM-4 expression in monocytes correlates with liver injury markers (ALT, AST, ALP, GGT, TBIL) and negatively with albumin.", "protein": "TIM-4/TIMD4", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Mucin-type O-glycosylation influences monocyte subset function.", "mechanism": "TIM-4 expression in intermediate monocytes is significantly higher in PHC patients than controls.", "protein": "TIM-4/TIMD4", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "N-glycosylation affects serum stability and immunogenicity.", "mechanism": "AFP is an established marker for PHC; diagnostic accuracy is improved when combined with sTIM-4.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "Primary hepatocellular carcinoma (PHC)", "glycan_involvement": "Glycosylation status may affect tissue localization and detection.", "mechanism": "Low TIM-4 expression in tumor tissue distinguishes malignant from benign hepatic lesions.", "protein": "TIM-4/TIMD4", "relationship_type": "biomarker", "source_pmcid": "PMC12350753" }, { "confidence": "high", "disease": "COVID-19-associated acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation of CD24 is essential for its immunomodulatory function.", "mechanism": "CD24-loaded EVs inhibit inflammatory responses via NF-\u03baB pathway modulation.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects CD24\u2019s interaction with damage-associated molecular patterns.", "mechanism": "EVs loaded with CD24 reduce lung inflammation and injury in sepsis models.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation modulates CD24\u2019s anti-inflammatory activity.", "mechanism": "CD24-EVs reduce airway inflammation and fibrosis.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycosylation required for CD24\u2019s regulatory effects.", "mechanism": "CD24-EVs inhibit fibrotic signaling in lung tissue.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "high", "disease": "Cancer (chronic myeloid leukemia, CML)", "glycan_involvement": "LAMP2B glycosylation may affect EV targeting and stability.", "mechanism": "Engineered EVs target IL3 receptor on CML cells, delivering siRNA and imatinib to inhibit tumor growth.", "protein": "LAMP2B-IL3 fusion", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "LAMP2B glycosylation may enhance EV stability and targeting.", "mechanism": "Engineered EVs cross blood\u2013brain barrier, deliver neuroprotective miRNA-124 to ischemic cortex.", "protein": "LAMP2B-RVG fusion", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation influences EV-cell interactions and immune recognition.", "mechanism": "Tetraspanin glycoproteins are enriched on EVs from tumor cells and may mediate immune modulation and metastasis.", "protein": "CD9/CD63/CD81", "relationship_type": "biomarker", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation critical for receptor function and cell targeting.", "mechanism": "EPC-EVs expressing these glycoproteins promote angiogenesis and tissue repair.", "protein": "VEGFR2/CD31/CD34", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Bone injury", "glycan_involvement": "Fibronectin glycosylation modulates matrix interactions.", "mechanism": "CREKA-modified EVs target fibrin-fibronectin complexes to enhance bone repair.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Idiopathic pulmonary fibrosis (IPF)", "glycan_involvement": "Glycosylation required for anti-fibrotic activity.", "mechanism": "CD24-EVs reduce fibrotic progression in lung tissue.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350758" }, { "confidence": "medium", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Involved in injury response and mononuclear cell migration across the blood-brain barrier; plasma levels not different between DRE and PNES.", "protein": "Chitinase 3-like 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "high", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "N-glycosylation modulates cell adhesion and migration.", "mechanism": "Increased expression on classical monocytes in DRE, indicating monocyte activation and potential CNS infiltration.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12350764" }, { "confidence": "high", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "Glycosylation affects receptor trafficking and function.", "mechanism": "Higher percentage of classical monocytes express P2X7R in DRE; involved in ATP-mediated pro-inflammatory signaling.", "protein": "P2X7 receptor (P2X7R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350764" }, { "confidence": "high", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "Glycosylation required for LPS binding and immune activation.", "mechanism": "Higher percentage of classical monocytes (CD14++CD16\u2212) in DRE, indicating a pro-inflammatory state.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "medium", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "Glycosylation modulates Fc receptor function.", "mechanism": "Lower percentage of non-classical monocytes (CD14\u2212CD16+) in DRE; non-classical monocytes are less pro-inflammatory.", "protein": "CD16", "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "medium", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "N-glycosylation critical for MHC class II stability and antigen presentation.", "mechanism": "Used to identify monocyte subsets; antigen presentation may be altered in DRE.", "protein": "HLADR (HLA-DR)", "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation required for function and secretion.", "mechanism": "Elevated in CSF and correlates with disease activity.", "protein": "Chitinase 3-like 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation modulates integrin-mediated adhesion.", "mechanism": "Increased monocyte CD11b expression correlates with cognitive impairment.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "medium", "disease": "Drug-resistant epilepsy (DRE)", "glycan_involvement": "Glycosylation affects receptor function.", "mechanism": "Activation leads to release of IL-1\u03b2 and IL-18, contributing to neuroinflammation and epileptogenesis.", "protein": "P2X7 receptor (P2X7R)", "relationship_type": "causal", "source_pmcid": "PMC12350764" }, { "confidence": "low", "disease": "REM sleep behavioral disturbance", "glycan_involvement": "N-glycosylation modulates integrin function.", "mechanism": "Increased monocyte activation marker CD11b reported.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350764" }, { "confidence": "high", "disease": "Bladder urothelial carcinoma (BLCA)", "glycan_involvement": "TRPM4 is a glycoprotein; glycosylation may affect channel stability and localization.", "mechanism": "TRPM4 is overexpressed due to promoter hypomethylation, serving as a diagnostic biomarker.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Cholangiocarcinoma (CHOL)", "glycan_involvement": "Glycosylation likely modulates TRPM4 trafficking and function.", "mechanism": "TRPM4 is significantly upregulated in tumor tissue, correlating with disease progression.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Ovarian serous cystadenocarcinoma (OV)", "glycan_involvement": "Glycosylation may influence TRPM4-mediated immune interactions.", "mechanism": "TRPM4 overexpression is associated with poor prognosis and immune infiltration.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Kidney renal clear cell carcinoma (KIRC)", "glycan_involvement": "Glycosylation status may affect channel activity and tumor suppression.", "mechanism": "TRPM4 is downregulated due to promoter hypermethylation; low expression is associated with better prognosis.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "protective", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Colon adenocarcinoma (COAD)", "glycan_involvement": "Glycosylation may regulate TRPM4 stability and signaling.", "mechanism": "TRPM4 downregulation (via promoter methylation) inhibits PI3K/Akt pathway, suppressing tumorigenesis.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "protective", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Prostate adenocarcinoma (PRAD)", "glycan_involvement": "Glycosylation may modulate TRPM4 surface expression.", "mechanism": "TRPM4 overexpression (due to hypomethylation) correlates with higher Gleason scores and diagnostic accuracy.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Uterine corpus endometrial carcinoma (UCEC)", "glycan_involvement": "Glycosylation may affect TRPM4 interaction with immune checkpoint ligands.", "mechanism": "TRPM4 mutations and high expression are linked to immune evasion; targeting TRPM4 or PVRL2 may enhance immunotherapy.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350802" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation may impact TRPM4 function in the tumor microenvironment.", "mechanism": "High TRPM4 expression is associated with poor survival, possibly via cell death resistance and immune modulation.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "risk factor", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Breast invasive carcinoma (BRCA)", "glycan_involvement": "Glycosylation may regulate TRPM4-mediated signaling and drug resistance.", "mechanism": "TRPM4 overexpression activates NF-\u03baB pathway, promoting multidrug resistance and cell survival.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "causal", "source_pmcid": "PMC12350802" }, { "confidence": "medium", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may influence TRPM4's immune regulatory functions.", "mechanism": "TRPM4 is downregulated and correlates with immune checkpoint signaling and poor prognosis.", "protein": "TRPM4", "protein_enriched": { "function": "Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellula", "gene_name": "TRPM4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8TD43" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350802" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "SOD is glycosylated for stability and activity; glycosylation may affect enzyme localization and function.", "mechanism": "Increased SOD activity neutralizes ROS, reducing oxidative stress and facilitating viral replication.", "protein": "Superoxide Dismutase (SOD)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12350806" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "CAT glycosylation influences secretion and activity; may be modulated during infection.", "mechanism": "Upregulated CAT activity detoxifies hydrogen peroxide, contributing to an antioxidant environment that supports viral replication.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC12350806" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "GPx glycosylation affects enzyme stability and function.", "mechanism": "GPx activity increases, reducing peroxides and maintaining redox balance, which helps viral immune evasion.", "protein": "Glutathione Peroxidase (GPx)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12350806" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "iNOS glycosylation is important for its activity and cellular localization.", "mechanism": "VACV infection downregulates iNOS expression, reducing NO production and limiting antiviral immune responses.", "protein": "Inducible Nitric Oxide Synthase (iNOS)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12350806" }, { "confidence": "high", "disease": "Vaccinia virus infection", "glycan_involvement": "Nrf2 glycosylation may regulate its stability and nuclear translocation.", "mechanism": "VACV activates Nrf2/ARE pathway, upregulating antioxidant enzymes and promoting an environment favorable for viral replication.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350806" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Viral SOD may be glycosylated for stability and host interaction.", "mechanism": "Viral SOD delivered by VACV lateral bodies directly reduces host ROS, aiding immune evasion.", "protein": "VACV A45R (viral SOD)", "relationship_type": "causal", "source_pmcid": "PMC12350806" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Glycosylation may affect viral protein-host interactions.", "mechanism": "Viral glutaredoxins modulate host redox environment, supporting viral replication.", "protein": "VACV O2L/G4L (viral glutaredoxin homologues)", "relationship_type": "causal", "source_pmcid": "PMC12350806" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Potential glycosylation may regulate activity.", "mechanism": "Thiol oxidoreductase activity contributes to antioxidant state, facilitating immune evasion.", "protein": "VACV A2.5L (thiol oxidoreductase)", "relationship_type": "causal", "source_pmcid": "PMC12350806" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "A51R stabilizes microtubules and suppresses ROS-dependent antiviral pathways.", "protein": "VACV A51R", "relationship_type": "causal", "source_pmcid": "PMC12350806" }, { "confidence": "medium", "disease": "Human cytomegalovirus (HCMV) infection", "glycan_involvement": "Nrf2 glycosylation may regulate its function in viral latency.", "mechanism": "HCMV infection upregulates Nrf2, increasing antioxidant capacity and supporting viral latency.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12350806" }, { "confidence": "high", "disease": "Liver injury/hepatotoxicity", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its serum stability and clearance.", "mechanism": "Elevated serum AST indicates hepatocellular damage after CFZ or CFZ-loaded MOF administration.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "Proteasome subunits can be glycosylated, affecting assembly and function.", "mechanism": "Carfilzomib irreversibly inhibits PSMB5, inducing apoptosis in myeloma cells.", "protein": "Proteasome subunit beta type-5 (PSMB5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350853" }, { "confidence": "high", "disease": "Liver injury/hepatotoxicity", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Increased MDA reflects lipid peroxidation and oxidative stress in liver after CFZ or MOF exposure.", "protein": "Malondialdehyde (MDA, marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "medium", "disease": "Kidney injury/nephrotoxicity", "glycan_involvement": "N-glycosylation modulates albumin half-life and renal filtration.", "mechanism": "Albumin is used in nanocarrier design and as a marker for renal function; its glycosylation status can affect renal handling.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "high", "disease": "Kidney injury/nephrotoxicity", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Elevated serum creatinine indicates nephrotoxicity after high-dose CFZ or MOF.", "protein": "Creatinine (marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation may affect proteasome assembly and substrate recognition.", "mechanism": "Proteasome inhibition leads to apoptosis in various cancer cells.", "protein": "Proteasome subunit beta type-5 (PSMB5)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12350853" }, { "confidence": "medium", "disease": "Diabetic complications", "glycan_involvement": "No direct glycan involvement.", "mechanism": "MDA is a marker of oxidative stress, which is implicated in diabetic complications.", "protein": "Malondialdehyde (MDA, marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "No direct glycan involvement.", "mechanism": "MDA elevation reflects oxidative damage in neurological diseases.", "protein": "Malondialdehyde (MDA, marker)", "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation affects AST serum levels.", "mechanism": "AST elevation can indicate liver involvement or toxicity during cancer therapy.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "low", "disease": "Cardiotoxicity", "glycan_involvement": "N-glycosylation influences albumin's antioxidant properties.", "mechanism": "Albumin levels can reflect systemic toxicity, including cardiac effects.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12350853" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "N-glycosylation may affect JAM-C localization and function.", "mechanism": "JAM-C is expressed by leukemic stem cells, maintaining self-renewal via cis-interaction with LRP5 and PDK1/AKT signaling.", "protein": "JAM-C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12350915" }, { "confidence": "medium", "disease": "Multiple Myeloma (MM)", "glycan_involvement": "N-glycosylation may regulate JAM-C cell surface expression.", "mechanism": "JAM-C overexpression in MM cells is associated with altered localization and CD138 downregulation, affecting disease progression.", "protein": "JAM-C", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)", "glycan_involvement": "N-glycosylation may influence JAM-C interactions in Schwann cells.", "mechanism": "Loss of JAM-C or PMP22 leads to mislocalization of JAM-C, causing myelin sheath defects and neuropathy.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Male Infertility", "glycan_involvement": "N-glycosylation may affect JAM-C-mediated cell interactions.", "mechanism": "JAM-C deletion arrests spermatid development, preventing sperm maturation due to failed recruitment of polarity proteins.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "medium", "disease": "Hydrocephalus", "glycan_involvement": "N-glycosylation may regulate JAM-C localization at tight junctions.", "mechanism": "Genetic deletion of JAM-C impairs ependymal cell barrier function, leading to hydrocephalus.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Systemic Inflammation", "glycan_involvement": "N-glycosylation may affect JAM-C susceptibility to cleavage.", "mechanism": "Proteolytic cleavage of JAM-C by neutrophil elastase disrupts endothelial barrier, promoting reverse neutrophil migration and systemic inflammation.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Barrier Dysfunction (Retinal/Brain)", "glycan_involvement": "N-glycosylation at specific sites regulates JAM-C localization and barrier integrity.", "mechanism": "JAM-C knockdown delays tight junction formation in retinal pigment epithelium and airway epithelia, impairing barrier function.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Motor Abnormalities", "glycan_involvement": "N-glycosylation may modulate JAM-C function in myelin maintenance.", "mechanism": "JAM-C deficiency in Schwann cells leads to myelin defects and motor abnormalities.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "medium", "disease": "Imbalanced Hematopoiesis", "glycan_involvement": "N-glycosylation may affect JAM-C-mediated cell adhesion in bone marrow niche.", "mechanism": "JAM-C deficiency disrupts LT-HSC anchoring, causing myeloid skewing.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "medium", "disease": "Cerebellar Migration Defects", "glycan_involvement": "N-glycosylation may influence JAM-C surface expression and neuronal migration.", "mechanism": "JAM-C regulates migration of cerebellar granule neurons via Par-3 and DCC interactions; deficiency impairs neuronal positioning.", "protein": "JAM-C", "relationship_type": "causal", "source_pmcid": "PMC12350915" }, { "confidence": "high", "disease": "Meningioma", "glycan_involvement": "Sulfation and galactosylation of ceramide (glycosylation step essential for biomarker function).", "mechanism": "Elevated plasma sulfatide reflects altered ceramide metabolism in meningioma; associated with tumor progression.", "protein": "3-O-Sulfogalactosylceramide (sulfatide)", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "high", "disease": "Meningioma", "glycan_involvement": "Complex glycosylation (sialylation) of ceramide backbone; glycan structure critical for function.", "mechanism": "Increased plasma ganglioside GA2 indicates meningioma presence; involved in cell adhesion, migration, and immune evasion.", "protein": "Ganglioside GA2", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation and sulfation of ceramide required for biomarker activity.", "mechanism": "Elevated sulfatide associated with tumor aggressiveness and invasiveness in glioblastoma.", "protein": "3-O-Sulfogalactosylceramide (sulfatide)", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Ganglioside glycan moiety mediates cell surface recognition.", "mechanism": "Gangliosides serve as clinical biomarkers for neuroblastoma.", "protein": "Ganglioside GA2", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation (sialylation) essential for cell surface marker function.", "mechanism": "Ganglioside expression marks cancer stem cells and promotes tumorigenesis.", "protein": "Ganglioside GA2", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycan structure mediates cell-cell and cell-matrix interactions.", "mechanism": "Increased ganglioside expression correlates with enhanced adhesion, growth, and migration in melanoma.", "protein": "Ganglioside GA2", "relationship_type": "biomarker", "source_pmcid": "PMC12350971" }, { "confidence": "medium", "disease": "Meningioma", "glycan_involvement": "Catalyzes galactosylation of ceramide, a key glycosylation step in sulfatide biosynthesis.", "mechanism": "UGT8 overexpression drives ceramide glycosylation, supporting tumor proliferation and inhibiting apoptosis.", "protein": "Ceramide galactosyltransferase (UGT8)", "protein_enriched": { "function": "Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi (PubMed:1532799, PubMed:8643456). Catalyzes the transfer of", "gene_name": "UGCG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q16739" }, "relationship_type": "causal", "source_pmcid": "PMC12350971" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT indicates hepatobiliary injury post-bosavirus transfusion.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351494" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "GLDH glycosylation may influence enzyme activity and release.", "mechanism": "Elevated GLDH reflects hepatocellular injury following bosavirus exposure.", "protein": "Glutamate dehydrogenase (GLDH)", "protein_enriched": { "function": "Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important in", "gene_name": "GLUD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00367" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351494" }, { "confidence": "high", "disease": "Hepatopathy", "glycan_involvement": "Viral glycoproteins may mediate host cell entry and immune evasion.", "mechanism": "Bosavirus infection via transfused plasma led to liver injury in the calf.", "protein": "Bosavirus capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12351494" }, { "confidence": "medium", "disease": "Serum hepatitis (Theiler's disease)", "glycan_involvement": "Glycosylation of viral capsid proteins affects infectivity and immune response.", "mechanism": "Copiparvovirus (EqPV-H) capsid glycoprotein is linked to serum hepatitis in horses; analogy drawn to bosavirus in cattle.", "protein": "Bosavirus capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12351494" }, { "confidence": "high", "disease": "Hypoproteinemia", "glycan_involvement": "Albumin glycosylation influences its half-life and function.", "mechanism": "Low albumin levels reflect impaired hepatic protein synthesis during hepatopathy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351494" }, { "confidence": "medium", "disease": "Hepatopathy", "glycan_involvement": "ALP glycosylation modulates enzyme activity and tissue localization.", "mechanism": "Elevated ALP may indicate biliary involvement in liver injury.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351494" }, { "confidence": "medium", "disease": "Hepatopathy", "glycan_involvement": "AST glycosylation can affect enzyme stability.", "mechanism": "AST elevation may reflect hepatocellular or muscle injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351494" }, { "confidence": "medium", "disease": "Portal hepatitis", "glycan_involvement": "Capsid glycoprotein glycosylation may influence tropism for hepatic cells.", "mechanism": "Bosavirus detected in liver tissue coincident with portal hepatitis.", "protein": "Bosavirus capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12351494" }, { "confidence": "medium", "disease": "Biliary hyperplasia", "glycan_involvement": "Viral glycoproteins may interact with biliary epithelium via glycan recognition.", "mechanism": "Bosavirus infection associated with mild biliary hyperplasia in calf liver.", "protein": "Bosavirus capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12351494" }, { "confidence": "low", "disease": "Mucosal disease", "glycan_involvement": "Capsid glycoprotein glycosylation may mediate mucosal cell infection.", "mechanism": "Bosavirus previously identified in calves with mucosal disease.", "protein": "Bosavirus capsid protein", "relationship_type": "causal", "source_pmcid": "PMC12351494" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "HAS1 synthesizes hyaluronic acid, a major ECM glycan.", "mechanism": "HAS1 overexpression in CAFs at the invasion front promotes ECM remodeling and OSCC invasion.", "protein": "HAS1", "relationship_type": "causal", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Lymph Node Metastasis", "glycan_involvement": "Increased HA alters ECM structure, facilitating metastasis.", "mechanism": "HAS1-high CAFs increase lymph node metastasis via ECM remodeling.", "protein": "HAS1", "relationship_type": "causal", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Poor Disease-Free Survival", "glycan_involvement": "HA-rich ECM correlates with aggressive tumor behavior.", "mechanism": "High HAS1 expression in CAFs at the invasion front predicts poor DFS in OSCC.", "protein": "HAS1", "relationship_type": "biomarker", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Epithelial-Mesenchymal Transition (EMT)", "glycan_involvement": "HA-rich ECM promotes EMT marker changes (\u2193E-cadherin, \u2191N-cadherin).", "mechanism": "HAS1-driven ECM remodeling induces EMT in OSCC cells.", "protein": "HAS1", "relationship_type": "causal", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Epithelial-Mesenchymal Transition (EMT)", "glycan_involvement": "E-cadherin is a glycoprotein; its loss is associated with EMT.", "mechanism": "Loss of E-cadherin in tumor cells at HAS1-high invasion front indicates EMT.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Epithelial-Mesenchymal Transition (EMT)", "glycan_involvement": "N-cadherin is a glycoprotein; its gain is associated with EMT.", "mechanism": "Upregulation of N-cadherin in tumor cells at HAS1-high invasion front indicates EMT.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Tumor Invasion", "glycan_involvement": "HA deposition disrupts ECM, facilitating invasion.", "mechanism": "HAS1-high CAFs remodel ECM, increasing OSCC cell invasion in vitro and in vivo.", "protein": "HAS1", "relationship_type": "causal", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Extracellular Matrix Remodeling", "glycan_involvement": "Direct synthesis of HA, a glycosaminoglycan.", "mechanism": "HAS1 upregulation in CAFs leads to increased HA production and ECM disorganization.", "protein": "HAS1", "relationship_type": "causal", "source_pmcid": "PMC12351772" }, { "confidence": "medium", "disease": "Recurrence", "glycan_involvement": "HA-rich ECM supports tumor regrowth.", "mechanism": "High HAS1 expression in CAFs at the invasion front correlates with higher recurrence rates.", "protein": "HAS1", "relationship_type": "biomarker", "source_pmcid": "PMC12351772" }, { "confidence": "medium", "disease": "Advanced Stage OSCC", "glycan_involvement": "Inhibition of HA synthesis disrupts pro-tumor ECM.", "mechanism": "Targeting HAS1-driven ECM remodeling may inhibit OSCC progression.", "protein": "HAS1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351772" }, { "confidence": "high", "disease": "Trisomy 21 (Down syndrome)", "glycan_involvement": "AFP-L2 is defined by its N-glycan structure and weak affinity for lens culinaris agglutinin.", "mechanism": "Elevated maternal serum AFP-L2 in first trimester predicts fetal trisomy 21.", "protein": "Alpha-fetoprotein variant L2 (AFP-L2)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Trisomy 18 (Edwards syndrome)", "glycan_involvement": "N-glycosylation variant; altered glycan structure may affect placental transport.", "mechanism": "Elevated maternal serum AFP-L2 in first trimester predicts fetal trisomy 18.", "protein": "Alpha-fetoprotein variant L2 (AFP-L2)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Neural tube defects (NTDs)", "glycan_involvement": "N-glycosylation defines AFP-L2 variant; increased levels reflect fetal protein leakage.", "mechanism": "Elevated maternal serum AFP-L2 in first trimester predicts fetal NTDs.", "protein": "Alpha-fetoprotein variant L2 (AFP-L2)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Trisomy 21 (Down syndrome)", "glycan_involvement": "Glycosylation affects stability and serum levels.", "mechanism": "Decreased maternal serum PAPP-A in first trimester associated with trisomy 21.", "protein": "Pregnancy-associated plasma protein A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Trisomy 18 (Edwards syndrome)", "glycan_involvement": "Glycosylation impacts detection and function.", "mechanism": "Decreased maternal serum PAPP-A in first trimester associated with trisomy 18.", "protein": "Pregnancy-associated plasma protein A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "medium", "disease": "Neural tube defects (NTDs)", "glycan_involvement": "Glycosylation may influence serum stability.", "mechanism": "Lower PAPP-A levels weakly associated with NTDs.", "protein": "Pregnancy-associated plasma protein A (PAPP-A)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Trisomy 21 (Down syndrome)", "glycan_involvement": "Glycosylation affects immunoreactivity and serum half-life.", "mechanism": "Elevated maternal serum free \u03b2-hCG in first trimester predicts trisomy 21.", "protein": "Free beta-subunit of human chorionic gonadotropin (free \u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Trisomy 18 (Edwards syndrome)", "glycan_involvement": "Glycosylation influences detection.", "mechanism": "Decreased maternal serum free \u03b2-hCG in first trimester associated with trisomy 18.", "protein": "Free beta-subunit of human chorionic gonadotropin (free \u03b2-hCG)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Neural tube defects (NTDs)", "glycan_involvement": "N-glycan structure enables variant-specific detection.", "mechanism": "AFP-L2 elevation reflects fetal protein leakage due to open neural tube.", "protein": "Alpha-fetoprotein variant L2 (AFP-L2)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "medium", "disease": "Trisomy 21 (Down syndrome)", "glycan_involvement": "N-glycosylation variant may affect placental transfer.", "mechanism": "AFP-L2 elevation may result from placental transport defect or altered glycosylation.", "protein": "Alpha-fetoprotein variant L2 (AFP-L2)", "relationship_type": "biomarker", "source_pmcid": "PMC12351824" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "TSH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "TSH levels and indices (TSHI, TT4RI, TFQI) are associated with glycemic control (TIR) in T2DM.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "FT4 is a glycoprotein hormone; glycosylation modulates its secretion and activity.", "mechanism": "FT4 levels are positively correlated with TIR, indicating better glycemic control.", "protein": "Free Thyroxine (FT4)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "FT3 is a glycoprotein hormone; glycosylation influences hormone stability.", "mechanism": "T3 inhibits \u03b2-cell apoptosis and promotes insulin secretion, supporting glucose homeostasis.", "protein": "Free Triiodothyronine (FT3)", "relationship_type": "protective", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Diabetic Peripheral Neuropathy", "glycan_involvement": "TSH glycosylation affects its bioactivity.", "mechanism": "Impaired TH sensitivity is associated with increased risk of neuropathy.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Diabetic Retinopathy", "glycan_involvement": "TSH glycosylation modulates receptor interaction.", "mechanism": "Impaired TH sensitivity correlates with retinopathy risk.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Diabetic Nephropathy", "glycan_involvement": "TSH glycosylation impacts renal signaling.", "mechanism": "Impaired TH sensitivity is linked to nephropathy.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Impaired Central Thyroid Hormone Sensitivity (TH Resistance)", "glycan_involvement": "A-FABP glycosylation may affect secretion and function.", "mechanism": "Elevated A-FABP correlates with reduced TH sensitivity, mediating adipose dysfunction.", "protein": "Fatty Acid Binding Protein (A-FABP)", "relationship_type": "causal", "source_pmcid": "PMC12351832" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "GLUT2 glycosylation is essential for membrane localization and function.", "mechanism": "THs upregulate GLUT2 expression, increasing hepatic glucose output.", "protein": "Glucose Transporter Protein 2 (GLUT2)", "relationship_type": "causal", "source_pmcid": "PMC12351832" }, { "confidence": "low", "disease": "Metabolism-Related Fatty Liver", "glycan_involvement": "TSH glycosylation may influence hepatic effects.", "mechanism": "Impaired TH sensitivity is associated with fatty liver.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "low", "disease": "Abdominal Obesity", "glycan_involvement": "TSH glycosylation affects metabolic signaling.", "mechanism": "Reduced TH sensitivity is linked to obesity; reversible after weight loss.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12351832" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "m5C RNA methylation (not classical glycosylation, but an RNA modification with similar regulatory impact)", "mechanism": "NSUN2 is overexpressed in CRC, promotes tumor growth and progression by stabilizing PHGDH mRNA via m5C methylation, enhancing serine metabolism.", "protein": "NSUN2", "protein_enriched": { "function": "RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, ", "gene_name": "NSUN2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70375MX", "G42581TG", "G49108TO" ], "uniprot_id": "Q08J23" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "m5C methylation of mRNA (not classical glycosylation)", "mechanism": "PHGDH is upregulated in CRC, drives serine biosynthesis and tumor cell survival; its expression is stabilized by NSUN2-mediated m5C methylation.", "protein": "PHGDH", "protein_enriched": { "function": "Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-", "gene_name": "PHGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43175" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12351839" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Recognition of m5C RNA modification (not classical glycosylation)", "mechanism": "ALYREF binds m5C-modified PHGDH mRNA, enhancing its stability and promoting CRC cell proliferation.", "protein": "ALYREF", "protein_enriched": { "function": "Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with", "gene_name": "ALYREF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86V81" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "m5C RNA methylation", "mechanism": "NSUN2 dysregulation associated with carcinogenesis via m5C RNA methylation.", "protein": "NSUN2", "protein_enriched": { "function": "RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, ", "gene_name": "NSUN2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70375MX", "G42581TG", "G49108TO" ], "uniprot_id": "Q08J23" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Esophageal carcinoma", "glycan_involvement": "m5C RNA methylation", "mechanism": "NSUN2 dysregulation associated with carcinogenesis via m5C RNA methylation.", "protein": "NSUN2", "protein_enriched": { "function": "RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, ", "gene_name": "NSUN2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70375MX", "G42581TG", "G49108TO" ], "uniprot_id": "Q08J23" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Stomach adenocarcinoma", "glycan_involvement": "m5C RNA methylation", "mechanism": "NSUN2 dysregulation associated with carcinogenesis via m5C RNA methylation.", "protein": "NSUN2", "protein_enriched": { "function": "RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, ", "gene_name": "NSUN2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70375MX", "G42581TG", "G49108TO" ], "uniprot_id": "Q08J23" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Liver hepatocellular carcinoma", "glycan_involvement": "m5C RNA methylation", "mechanism": "NSUN2 dysregulation associated with carcinogenesis via m5C RNA methylation.", "protein": "NSUN2", "protein_enriched": { "function": "RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, ", "gene_name": "NSUN2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70375MX", "G42581TG", "G49108TO" ], "uniprot_id": "Q08J23" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "Not specified", "mechanism": "PHGDH upregulation promotes tumorigenesis via serine biosynthesis.", "protein": "PHGDH", "protein_enriched": { "function": "Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-", "gene_name": "PHGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43175" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Not specified", "mechanism": "PHGDH upregulation promotes tumorigenesis via serine biosynthesis.", "protein": "PHGDH", "protein_enriched": { "function": "Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-", "gene_name": "PHGDH", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43175" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "m5C RNA modification recognition", "mechanism": "ALYREF enhances mRNA stability of oncogenes (e.g., EGFR) via m5C binding, promoting tumor progression.", "protein": "ALYREF", "protein_enriched": { "function": "Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with", "gene_name": "ALYREF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86V81" }, "relationship_type": "causal", "source_pmcid": "PMC12351839" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation at Asn62/Asn115 regulates trafficking, secretion, and activity in microglia and monocytes.", "mechanism": "Upregulated in microglia and peripheral monocytes; inhibits cathepsins, impairs A\u03b2 clearance, promotes neuroinflammation and neurodegeneration.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for proper lysosomal targeting and function.", "mechanism": "Early upregulation during tau pathology slows tau aggregation and cognitive decline via DAM activation.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "protective", "source_pmcid": "PMC12351862" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation directs lysosomal localization in microglia.", "mechanism": "Upregulated in acute demyelination; inhibits cathepsin C, reduces inflammation, promotes remyelination.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation status affects secretion vs. lysosomal targeting.", "mechanism": "Downregulated in chronic phase via miR29a and ELAVL1; loss impairs remyelination.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "N-glycosylation required for microglial trafficking and function.", "mechanism": "Upregulated in activated microglia; promotes neuroinflammation and dopaminergic neuron loss; inhibition reduces pathology.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "N-glycosylation mediates microglial localization.", "mechanism": "Upregulated in microglia during early and late disease; may regulate microglial activation and tissue repair.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Stroke (ischemic brain injury)", "glycan_involvement": "N-glycosylation required for secretion and lysosomal targeting in microglia.", "mechanism": "Upregulated in acute phase; enhances neuroinflammation via A2AR-PKA/PKC-CREB signaling.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Aicardi\u2013Gouti\u00e8res syndrome", "glycan_involvement": "N-glycosylation required for secretion and immune cell uptake.", "mechanism": "Increased with age; inhibits cathepsins in T cells, suppresses cytotoxicity, protects against IFN-\u03b1\u2013mediated inflammation.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12351862" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation at Asn115 promotes secretion into tumor microenvironment.", "mechanism": "Secreted by tumor and immune cells; inhibits cathepsins in NK/T cells (immune evasion), but also reduces tumor invasiveness.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "dual (protective/pathological)/therapeutic_target", "source_pmcid": "PMC12351862" }, { "confidence": "low", "disease": "Osteoporosis in AD", "glycan_involvement": "N-glycosylation facilitates secretion and function in monocytes.", "mechanism": "Upregulated in monocytes; promotes osteoclast differentiation and bone resorption, contributing to osteoporosis in AD.", "protein": "Cystatin F", "protein_enriched": { "function": "", "gene_name": "HSPB7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBY9" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12351862" }, { "confidence": "high", "disease": "Central diabetes insipidus (CDI)", "glycan_involvement": "Glycosylation affects ADH stability and secretion.", "mechanism": "Impaired production or secretion of ADH leads to CDI.", "protein": "Antidiuretic hormone (ADH, vasopressin)", "relationship_type": "causal", "source_pmcid": "PMC12351867" }, { "confidence": "medium", "disease": "Central diabetes insipidus (CDI)", "glycan_involvement": "Glycosylation may affect peptide stability and receptor interaction.", "mechanism": "Ectopic secretion by lung tumors may inhibit ADH release, causing CDI.", "protein": "Beta-endorphin", "relationship_type": "causal", "source_pmcid": "PMC12351867" }, { "confidence": "low", "disease": "Central diabetes insipidus (CDI)", "glycan_involvement": "Glycosylation influences protein function and clearance.", "mechanism": "Ectopic secretion by tumors may inhibit ADH release.", "protein": "Beta-lipoprotein", "relationship_type": "causal", "source_pmcid": "PMC12351867" }, { "confidence": "low", "disease": "Central diabetes insipidus (CDI)", "glycan_involvement": "Glycosylation may affect peptide activity.", "mechanism": "Ectopic secretion by lung tumors may inhibit ADH release.", "protein": "Leu-enkephalin", "relationship_type": "causal", "source_pmcid": "PMC12351867" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation may affect protein stability and detection.", "mechanism": "TTF-1 expression is used for diagnosis of lung adenocarcinoma.", "protein": "Thyroid transcription factor-1 (TTF-1)", "protein_enriched": { "function": "Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differe", "gene_name": "NKX2-1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43699" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation affects enzyme activity and immunodetection.", "mechanism": "Napsin A is a diagnostic marker for lung adenocarcinoma.", "protein": "Napsin A", "protein_enriched": { "function": "May be involved in processing of pneumocyte surfactant precursors", "gene_name": "NAPSA", "glycan_count": 76, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G07246CJ", "G07755XJ", "G08290VR", "G08918WF", "G10819WX", "G11314AS", "G12341GU", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23505EP", "G23719VF", "G25079LO", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G35029YA", "G36379GD", "G37412TK", "G37509XX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43769HG", "G45395BF", "G45504EY", "G47644PP", "G49018RC", "G49906RN", "G49955PK", "G50282JC", "G54010QB", "G57317CE", "G57776ZU", "G58954YZ", "G60033FS", "G62765YT", "G63980BQ", "G65184UU", "G68490OW", "G69521XL", "G70619PT", "G72787SB", "G72790NZ", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83633GK", "G83646BJ", "G84225JN", "G84349RE", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G87123QX", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92050GC", "G92275SC", "G95177YH", "G95865ZB" ], "uniprot_id": "O96009" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation may influence protein function.", "mechanism": "p63 expression helps differentiate lung cancer subtypes.", "protein": "p63", "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation affects filament assembly and immunoreactivity.", "mechanism": "CK5/6 negativity supports adenocarcinoma diagnosis.", "protein": "Cytokeratin 5/6 (CK5/6)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "medium", "disease": "Paraneoplastic syndromes", "glycan_involvement": "Glycosylation is essential for CRP function and clearance.", "mechanism": "Elevated CRP indicates inflammation, often seen in PNS.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "medium", "disease": "Metastatic bone lesions", "glycan_involvement": "Glycosylation affects enzyme activity and serum levels.", "mechanism": "Elevated ALP reflects bone metastasis.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351867" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is N- and O-glycosylated, which can affect its processing and trafficking.", "mechanism": "APP is cleaved by BACE1 and \u03b3-secretase to generate A\u03b2, which aggregates into plaques driving AD pathology.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC12351871" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "BACE1 is N-glycosylated, which is important for its folding, stability, and trafficking.", "mechanism": "BACE1 initiates the amyloidogenic cleavage of APP, leading to A\u03b2 production; inhibition reduces A\u03b2 generation.", "protein": "BACE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351871" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 can be O-glycosylated, which may influence aggregation and clearance.", "mechanism": "A\u03b2 aggregates form plaques, causing synaptic damage, neuroinflammation, and neuronal death.", "protein": "A\u03b2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12351871" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "MBP is glycosylated, which may affect its interaction with A\u03b2.", "mechanism": "MBP inhibits A\u03b2 fibril formation; its deficiency is associated with AD progression.", "protein": "MBP", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12351871" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is glycosylated, which may modulate its filament assembly.", "mechanism": "GFAP upregulation marks astrocyte activation and neuroinflammation in AD.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351871" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Iba1 is glycosylated, potentially affecting its function in microglia.", "mechanism": "Iba1 marks microglial activation, which is involved in A\u03b2 clearance and neuroinflammation.", "protein": "Iba1", "relationship_type": "biomarker", "source_pmcid": "PMC12351871" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "nAChRs are N-glycosylated, influencing receptor assembly and function.", "mechanism": "nAChRs mediate neuronal signaling; targeted for brain delivery of therapeutics in AD.", "protein": "nAChR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351871" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation of BACE1 affects its localization and function in microglia.", "mechanism": "BACE1 in microglia modulates A\u03b2 phagocytosis; its inhibition enhances A\u03b2 clearance.", "protein": "BACE1", "relationship_type": "causal", "source_pmcid": "PMC12351871" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation may affect A\u03b21-42 aggregation and detection.", "mechanism": "A\u03b21-42 levels in brain and exosomes reflect AD pathology and therapeutic response.", "protein": "A\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC12351871" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation state of APP influences its cleavage by BACE1.", "mechanism": "Modulating APP processing (via BACE1 inhibition) reduces A\u03b2 production.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351871" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycosylation affects P-glycoprotein stability and function, influencing its role in drug and nutrient transport.", "mechanism": "Inhibition by grapefruit juice alters drug metabolism, potentially impacting nutrient absorption and muscle function relevant to frailty.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycosylation modulates CYP3A4 folding and activity, impacting its metabolic capacity.", "mechanism": "Grapefruit juice inhibits CYP3A4, affecting metabolism of drugs and possibly nutrients, which may contribute to frailty.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation is essential for P-glycoprotein trafficking and function in muscle and other tissues.", "mechanism": "Altered P-glycoprotein activity (via grapefruit juice) may affect muscle metabolism and drug-nutrient interactions, influencing sarcopenia risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation affects enzyme stability and substrate specificity.", "mechanism": "Inhibition by grapefruit juice may disrupt metabolic pathways relevant to muscle maintenance.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Low appendicular lean mass (ALM)", "glycan_involvement": "Glycosylation modulates transporter efficiency.", "mechanism": "Inhibition may impair nutrient absorption, contributing to reduced muscle mass.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Low appendicular lean mass (ALM)", "glycan_involvement": "Glycosylation influences enzyme function.", "mechanism": "Altered drug/nutrient metabolism may affect muscle mass.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Low hand grip strength (LHGS)", "glycan_involvement": "Glycosylation required for proper function.", "mechanism": "Potential impact on muscle function via altered pharmacokinetics.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "low", "disease": "Low hand grip strength (LHGS)", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Disrupted metabolism may indirectly affect muscle strength.", "protein": "Cytochrome P450 3A4", "relationship_type": "causal", "source_pmcid": "PMC12351878" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "GLP-1 is O-glycosylated, affecting stability and receptor interaction.", "mechanism": "GLP-1 regulates glucose homeostasis and insulin secretion; increased by Caulerpa extract, improving glycemic control.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "TNF-\u03b1 glycosylation modulates secretion and activity.", "mechanism": "TNF-\u03b1 is a pro-inflammatory cytokine elevated in metabolic syndrome; Caulerpa extract reduces TNF-\u03b1 levels.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-10 glycosylation affects stability and anti-inflammatory function.", "mechanism": "IL-10 is anti-inflammatory; Caulerpa extract increases IL-10, counteracting inflammation in MetS.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12351937" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "PGC-1\u03b1 regulates mitochondrial biogenesis and energy metabolism; increased by Caulerpa extract, improving metabolic efficiency.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351937" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "AKT1 regulates glucose uptake and lipid metabolism; Caulerpa extract enhances AKT1 activity, improving insulin sensitivity.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "No direct glycosylation reported.", "mechanism": "PPARG regulates adipogenesis and insulin sensitivity; Caulerpa extract modulates PPARG, reducing adiposity.", "protein": "PPARG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "AST is glycosylated, affecting secretion and stability.", "mechanism": "Elevated AST indicates liver/metabolic stress; Caulerpa extract lowers AST, suggesting hepatoprotection.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation affects enzyme activity and substrate specificity.", "mechanism": "\u03b1-glucosidase inhibition by Caulerpa extract reduces postprandial glucose spikes.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation modulates enzyme stability and activity.", "mechanism": "\u03b1-amylase inhibition by Caulerpa extract reduces carbohydrate digestion and glucose absorption.", "protein": "\u03b1-amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects enzyme secretion and activity.", "mechanism": "Lipase inhibition by Caulerpa extract reduces lipid absorption, improving lipid profiles.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351937" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "N-glycosylation affects stability and clearance.", "mechanism": "Elevated serum cystatin C reflects impaired glomerular filtration.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation modulates albumin half-life and vascular permeability.", "mechanism": "Low serum albumin is associated with increased AKI risk due to capillary leakage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "CRP glycosylation affects its immunomodulatory function.", "mechanism": "Elevated CRP indicates systemic inflammation, correlating with AKI severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "low", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may affect receptor binding and hormone stability.", "mechanism": "Vasopressin use reflects hypovolemia and increased AKI risk.", "protein": "Vasopressin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12351976" }, { "confidence": "low", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation can influence CK-MB serum levels.", "mechanism": "Elevated CK-MB may indicate muscle injury and correlate with AKI in critical illness.", "protein": "CK-MB (Creatine kinase MB)", "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation impacts renal clearance.", "mechanism": "Chronic elevation of cystatin C is a marker for CKD progression.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "low", "disease": "Acute Pancreatitis (AP)", "glycan_involvement": "Glycosylation status may affect inflammatory response.", "mechanism": "Hypoalbuminemia is common in AP due to inflammation and leakage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "medium", "disease": "Acute Pancreatitis (AP)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in AP and predicts severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "low", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may affect protein function and calcium binding.", "mechanism": "Serum calcium levels (and related proteins) show U-shaped correlation with AKI risk.", "protein": "Calcium-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12351976" }, { "confidence": "low", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation regulates channel trafficking and function.", "mechanism": "Hyperkalemia and potassium variability are predictors of AKI.", "protein": "Potassium channel glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12351976" }, { "confidence": "high", "disease": "Chronic Neutrophilic Leukemia (CNL)", "glycan_involvement": "Loss of O- or N-glycosylation at specific sites (T618, N610) enables constitutive activation.", "mechanism": "Activating mutations (e.g., T618I, N610S) drive ligand-independent signaling, leading to neutrophil proliferation.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "causal", "source_pmcid": "PMC12351999" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Disruption of N-glycosylation (N610) or O-glycosylation (T618) leads to ligand-independent signaling.", "mechanism": "Mutations (e.g., T618I, N610S, truncations) activate JAK-STAT, PI3K-AKT, and MAPK-ERK pathways, promoting leukemogenesis.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "causal", "source_pmcid": "PMC12351999" }, { "confidence": "medium", "disease": "Atypical Chronic Myeloid Leukemia (aCML)", "glycan_involvement": "Loss of glycosylation at T618/N610 implicated in activation.", "mechanism": "CSF3R mutations (e.g., T618I) found in up to 40% of aCML cases, activating downstream proliferation pathways.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "causal", "source_pmcid": "PMC12351999" }, { "confidence": "medium", "disease": "Chronic Myelomonocytic Leukemia (CMML)", "glycan_involvement": "Likely similar glycosylation disruption as in CNL/AML.", "mechanism": "CSF3R mutations present in ~4% of CMML, associated with disease phenotype.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12351999" }, { "confidence": "medium", "disease": "Myelodysplastic Syndrome (MDS)", "glycan_involvement": "Loss of glycosylation not directly implicated in these variants.", "mechanism": "Germline loss-of-function mutations (e.g., W547*) impair receptor expression and signaling, predisposing to MDS.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12351999" }, { "confidence": "low", "disease": "Multiple Myeloma", "glycan_involvement": "A119T may affect G-CSF sensitivity, glycosylation status unclear.", "mechanism": "Germline CSF3R variants (e.g., A119T, P784T) found in some multiple myeloma patients.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12351999" }, { "confidence": "low", "disease": "B-cell Acute Lymphoblastic Leukemia (B-ALL)", "glycan_involvement": "Potential effect on glycosylation and receptor function.", "mechanism": "Germline CSF3R A119T variant found in B-ALL; functional impact on glycosylation not detailed.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC12351999" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML) with CEBPA mutations", "glycan_involvement": "Glycosylation loss at T618/N610 enables CSF3R activation.", "mechanism": "CSF3R mutations synergize with CEBPA mutations to drive high-risk AML; order of mutations affects leukemogenesis.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12351999" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML) with RUNX1::ETO", "glycan_involvement": "Glycosylation loss at T618/N610 enables CSF3R activation.", "mechanism": "RUNX1::ETO translocation followed by CSF3R mutation (e.g., T618I) cooperates to drive AML.", "protein": "CSF3R (G-CSF receptor)", "relationship_type": "causal", "source_pmcid": "PMC12351999" }, { "confidence": "medium", "disease": "Myeloproliferative Neoplasms (MPN)", "glycan_involvement": "CALR is an ER chaperone for glycoprotein folding; mutant CALR alters glycoprotein maturation.", "mechanism": "CALR mutations are preleukemic drivers in MPN, affecting glycoprotein folding and signaling.", "protein": "CALR (Calreticulin)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12351999" }, { "confidence": "high", "disease": "Long COVID", "glycan_involvement": "ACE2 glycosylation modulates viral binding and infectivity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; miR-200c inhibits ACE2 expression, affecting viral entry and tissue injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "TMPRSS2 glycosylation affects protease activity and viral entry.", "mechanism": "TMPRSS2 primes SARS-CoV-2 spike for cell entry; miR-98-5p targets TMPRSS2, reducing infection.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "high", "disease": "Pulmonary fibrosis", "glycan_involvement": "TGF-\u03b21 is a secreted glycoprotein; glycosylation affects secretion and activity.", "mechanism": "TGF-\u03b21/Smad pathway drives fibrosis; miR-21 upregulates, miR-29 downregulates this pathway.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Gastrointestinal dysfunction", "glycan_involvement": "GP130 glycosylation is essential for receptor function.", "mechanism": "miR-31 prevents GP130 expression, modulating cytokine signaling and intestinal barrier stability.", "protein": "GP130", "relationship_type": "protective", "source_pmcid": "PMC12352008" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-6R glycosylation required for ligand binding.", "mechanism": "IL-6 receptor blockade (e.g., Tocilizumab) reduces miR-21, limiting cytokine storm.", "protein": "IL-6 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Myocarditis/Heart failure", "glycan_involvement": "PTEN glycosylation may affect stability and localization.", "mechanism": "miR-21 inhibits PTEN, promoting fibrosis and cardiac dysfunction.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Myocarditis/Heart failure", "glycan_involvement": "SPRY1 glycosylation may modulate function.", "mechanism": "miR-21 inhibits SPRY1, enhancing fibrotic signaling.", "protein": "SPRY1", "protein_enriched": { "function": "Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). Thereby acts as an antagonist of FGF-induced retinal lens fiber differen", "gene_name": "SPRY2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43597" }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Gastrointestinal dysfunction", "glycan_involvement": "NLRP3 glycosylation may regulate inflammasome assembly.", "mechanism": "miR-223 restrains NLRP3 inflammasome; deficiency leads to excessive IL-1\u03b2 and gut inflammation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Neuroinflammation/Cognitive impairment", "glycan_involvement": "STAT3 glycosylation may affect nuclear translocation.", "mechanism": "miR-124 downregulates STAT3, reducing neuroinflammation.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "protective", "source_pmcid": "PMC12352008" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Smad glycosylation may influence signaling efficiency.", "mechanism": "miR-192 and miR-200 upregulate TGF-\u03b2/Smad signaling, promoting renal fibrosis.", "protein": "Smad proteins", "relationship_type": "causal", "source_pmcid": "PMC12352008" }, { "confidence": "high", "disease": "NSTEACS", "glycan_involvement": "Glycosylation affects stability and clearance.", "mechanism": "Released during myocardial injury; elevated levels indicate acute coronary syndrome.", "protein": "Cardiac troponin T (cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates secretion and half-life.", "mechanism": "Elevated in response to ventricular stretch; predicts heart failure risk.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "medium", "disease": "NSTEACS", "glycan_involvement": "Glycosylation influences enzyme activity and detection.", "mechanism": "Released from damaged cardiac muscle; used for diagnosis.", "protein": "CK-MB", "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "medium", "disease": "Hypoalbuminaemia", "glycan_involvement": "Glycosylation affects stability and vascular transport.", "mechanism": "Low serum albumin indicates poor prognosis and comorbidity burden.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "medium", "disease": "MACEs", "glycan_involvement": "Glycosylation modulates peptide stability.", "mechanism": "Elevated NT-proBNP predicts increased risk of MACEs in NSTEACS.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "medium", "disease": "MACEs", "glycan_involvement": "Glycosylation may affect immunodetection.", "mechanism": "High cTnT levels correlate with increased MACEs risk.", "protein": "Cardiac troponin T (cTnT)", "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "medium", "disease": "NSTEACS", "glycan_involvement": "Glycosylation impacts albumin function.", "mechanism": "Hypoalbuminaemia is associated with worse outcomes in NSTEACS.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "low", "disease": "NSTEACS", "glycan_involvement": "Glycosylation affects enzyme stability.", "mechanism": "Elevated AST reflects cardiac or hepatic injury in NSTEACS.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "low", "disease": "NSTEACS", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "Elevated ALT may indicate comorbid hepatic involvement in NSTEACS.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "low", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation modulates peptide clearance.", "mechanism": "Elevated NT-proBNP is associated with arrhythmia risk in NSTEACS.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12352207" }, { "confidence": "high", "disease": "Myelosuppression", "glycan_involvement": "IgG4 glycosylation affects antibody stability and effector function.", "mechanism": "Immune checkpoint inhibition leads to immune-mediated hematopoietic suppression, exacerbated by chemotherapy.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "Fc glycosylation modulates antibody-mediated immune responses.", "mechanism": "Immune activation via PD-1 blockade triggers hepatic inflammation and cytotoxicity.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "high", "disease": "Rash", "glycan_involvement": "Glycosylation influences antibody half-life and tissue distribution.", "mechanism": "Immune-related skin inflammation due to enhanced T-cell activity.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Autoimmune lung disease", "glycan_involvement": "Glycosylation may affect antibody effector function in tissues.", "mechanism": "Immune checkpoint blockade induces lung autoimmunity.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Myocarditis", "glycan_involvement": "IgG4 glycosylation impacts immune cell recruitment.", "mechanism": "Immune-mediated cardiac inflammation following PD-1 inhibition.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation may influence antibody clearance and immune modulation.", "mechanism": "Immune checkpoint inhibition triggers thyroid autoimmunity.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Toxic epidermal necrolysis", "glycan_involvement": "Glycosylation affects antibody stability and immune activation.", "mechanism": "Severe immune-mediated skin reaction due to PD-1 blockade.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Immune-related hepatitis via T-cell activation.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Anaemia", "glycan_involvement": "Glycosylation influences antibody-mediated cell clearance.", "mechanism": "Immune-mediated destruction or suppression of erythroid lineage.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "medium", "disease": "Neutropenia", "glycan_involvement": "Glycosylation affects antibody effector function and immune cell interactions.", "mechanism": "Immune-mediated neutrophil depletion, especially with chemotherapy.", "protein": "Tislelizumab", "relationship_type": "causal", "source_pmcid": "PMC12352749" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Regulates O-glycosylation levels in CRC cells.", "mechanism": "Promotes CRC cell proliferation, migration, and reduces CD8+ T cell infiltration; knockdown decreases O-glycosylation and tumor aggressiveness.", "protein": "CCDC85B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354152" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Associated with increased O-glycosylation.", "mechanism": "High expression correlates with poor prognosis and lower survival rates.", "protein": "CCDC85B", "relationship_type": "biomarker", "source_pmcid": "PMC12354152" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation is essential for CEA function as a biomarker.", "mechanism": "Elevated postoperative CEA levels predict increased risk of CRC recurrence.", "protein": "CEA (Carcinoembryonic antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosyltransferase activity affects glycosylation patterns in CRC.", "mechanism": "Altered expression serves as a potential tumor biomarker.", "protein": "GLT8D1", "relationship_type": "biomarker", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosyltransferase activity affects glycosylation patterns in CRC.", "mechanism": "Altered expression serves as a potential tumor biomarker.", "protein": "GLT8D2", "relationship_type": "biomarker", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosyltransferase activity affects glycosylation patterns in CRC.", "mechanism": "Altered expression serves as a potential tumor biomarker.", "protein": "B4GALNT2", "protein_enriched": { "function": "Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity)", "gene_name": "NBEA", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G32392SM", "G49108TO", "G37399XV", "G28681TP", "G75230KT" ], "uniprot_id": "Q8NFP9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354152" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation (bisecting glycans) on IFN\u03b3R\u03b1.", "mechanism": "Restores sensitivity to IFN-\u03b3 by increasing bisecting glycan formation, overcoming N-glycosylation-mediated drug resistance.", "protein": "MGAT3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "O-GlcNAc modification at Ser49.", "mechanism": "O-GlcNAc glycosylation at Ser49 by OGT promotes nuclear translocation and drug resistance; inhibition re-sensitizes cells to CDK4/6 inhibitors.", "protein": "MITF (via O-GlcNAc glycosylation)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Immune evasion in cancer", "glycan_involvement": "Hyperglycosylation of pSAP.", "mechanism": "Hyperglycosylation induced by TGF-\u03b2 in dendritic cells leads to secretion and immune evasion.", "protein": "Prosaposin (pSAP)", "relationship_type": "causal", "source_pmcid": "PMC12354152" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Glycosylation status influences stromal interactions.", "mechanism": "Correlates with stromal remodeling and fibroblast infiltration, impacting tumor microenvironment.", "protein": "MYL9", "relationship_type": "causal", "source_pmcid": "PMC12354152" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns of AFP (e.g., increased fucosylation) are associated with HCC progression.", "mechanism": "Elevated serum AFP is used as a diagnostic and prognostic marker in HCC.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354724" }, { "confidence": "medium", "disease": "Extrahepatic metastasis of HCC", "glycan_involvement": "Glycoforms of AFP (e.g., AFP-L3) are linked to metastatic potential.", "mechanism": "High AFP levels may indicate increased risk of metastasis.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354724" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation may affect albumin stability and function in liver disease.", "mechanism": "Serum albumin is used to assess liver function and prognosis in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354724" }, { "confidence": "medium", "disease": "Extrahepatic metastasis of HCC", "glycan_involvement": "Glycosylation status may modulate albumin's half-life and bioactivity.", "mechanism": "Low serum albumin is an independent risk factor for metastasis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354724" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "HBsAg is a glycoprotein; its glycosylation is essential for viral infectivity and immune evasion.", "mechanism": "Chronic HBV infection (HBsAg positive) increases HCC risk.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12354724" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation of HBsAg modulates host immune response.", "mechanism": "Chronic HBV infection leads to cirrhosis, predisposing to HCC.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal", "source_pmcid": "PMC12354724" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "Inhibition reduces carbohydrate breakdown and glucose absorption.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation modulates enzyme function.", "mechanism": "Inhibition slows glucose release from dietary carbohydrates.", "protein": "Beta-glucosidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation regulates DPP-4 activity and cell surface localization.", "mechanism": "Inhibition increases incretin levels, enhancing insulin secretion.", "protein": "Dipeptidyl peptidase 4 (DPP-4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may affect receptor function and ligand binding.", "mechanism": "Activation improves insulin sensitivity and glucose metabolism.", "protein": "PPARG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation influences transporter stability and activity.", "mechanism": "Inhibition reduces renal glucose reabsorption.", "protein": "SGLT-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation stabilizes enzyme structure.", "mechanism": "Detoxifies hydrogen peroxide, reducing oxidative damage.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation affects enzyme activity.", "mechanism": "Detoxifies reactive intermediates, protecting cells.", "protein": "GST", "relationship_type": "protective", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Upregulation increases NO production, contributing to diabetic complications.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal", "source_pmcid": "PMC12354745" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation regulates enzyme localization and activity.", "mechanism": "Elevated expression increases NO, linked to vascular dysfunction.", "protein": "eNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor", "gene_name": "NOS3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G58001LT" ], "uniprot_id": "P29474" }, "relationship_type": "causal", "source_pmcid": "PMC12354745" }, { "confidence": "low", "disease": "Diabetic neuropathy", "glycan_involvement": "Glycosylation impacts transporter function in neural cells.", "mechanism": "Inhibition may reduce glucose toxicity in neural tissues.", "protein": "SGLT-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354745" }, { "confidence": "high", "disease": "Esophagogastric variceal bleeding (EGVB)", "glycan_involvement": "D-dimer is a glycosylated degradation product of fibrin.", "mechanism": "Reflects fibrinolysis and coagulation activation; elevated in cirrhosis and EGVB, associated with prognosis.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "high", "disease": "Esophagogastric variceal bleeding (EGVB)", "glycan_involvement": "FDPs are derived from glycosylated fibrinogen.", "mechanism": "Indicates hyperfibrinolysis and coagulation dysfunction; higher levels predict poor prognosis.", "protein": "Fibrinogen degradation products (FDPs)", "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Albumin is N-glycosylated; glycosylation status may affect half-life and function.", "mechanism": "Low serum albumin reflects impaired liver synthetic function and worse prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "APOA1 is glycosylated, which may affect lipid transport.", "mechanism": "Decreased APOA1 is associated with liver dysfunction and poor prognosis.", "protein": "Apolipoprotein A1 (APOA1)", "protein_enriched": { "function": "Glycinin is the major seed storage protein of soybean (PubMed:2485233). Glycinin basic peptides (GBPs), and, to a lower extent, glycinin exhibit antibacterial activity against Gram-negative and Gram-p", "gene_name": "GY1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04776" }, "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "APOB is heavily N-glycosylated, influencing secretion and stability.", "mechanism": "Lower APOB levels reflect impaired hepatic lipoprotein synthesis.", "protein": "Apolipoprotein B (APOB)", "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "medium", "disease": "Esophageal varices in cirrhosis", "glycan_involvement": "YAP1 is a glycoprotein; glycosylation may regulate its stability.", "mechanism": "Elevated plasma YAP1 correlates with variceal development and progression.", "protein": "YAP1", "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "medium", "disease": "Esophageal varices in cirrhosis", "glycan_involvement": "Cystatin C is N-glycosylated, affecting its serum levels.", "mechanism": "Cystatin C/albumin ratio predicts presence of varices.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12354750" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is heavily glycosylated, influencing epitope exposure and immune evasion.", "mechanism": "HR1 domain is targeted by broadly neutralizing antibody 3D1, blocking membrane fusion and viral entry.", "protein": "Spike protein (S) [SARS-CoV-2]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates accessibility of HR1 epitope.", "mechanism": "HR1 domain is conserved and targeted by 3D1, enabling cross-neutralization.", "protein": "Spike protein (S) [SARS-CoV-1]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation may shield HR1, but 3D1 recognizes exposed motif during fusion.", "mechanism": "3D1 binds to conserved HR1 motif in MERS-CoV spike, neutralizing pseudovirus.", "protein": "Spike protein (S) [MERS-CoV]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "gp41 is glycosylated; glycan shield affects antibody access.", "mechanism": "3D1 binds conserved NHR motif in gp41, suggesting potential cross-neutralization.", "protein": "gp41 [HIV-1]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "medium", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation may affect epitope exposure.", "mechanism": "3D1 binds LIKNQN motif in Marburgvirus GP, indicating possible broad antiviral activity.", "protein": "GP [Marburgvirus]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "high", "disease": "Common cold (HCoV-229E)", "glycan_involvement": "Glycosylation influences epitope accessibility.", "mechanism": "3D1 binds HR1C motif in HCoV-229E spike, neutralizing pseudovirus.", "protein": "Spike protein (S) [HCoV-229E]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "high", "disease": "Common cold (HCoV-NL63)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "3D1 binds HR1C motif in HCoV-NL63 spike, neutralizing pseudovirus.", "protein": "Spike protein (S) [HCoV-NL63]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "medium", "disease": "Canine coronavirus infection", "glycan_involvement": "Glycosylation may affect motif exposure.", "mechanism": "3D1 binds N-terminal HR1 motif in CCoV-HuPn-2018 spike, neutralizing pseudovirus.", "protein": "Spike protein (S) [CCoV-HuPn-2018]", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354777" }, { "confidence": "high", "disease": "COVID-19 (Omicron variant)", "glycan_involvement": "Glycosylation plus mutation alters epitope accessibility.", "mechanism": "Q954H mutation in HR1 motif disrupts 3D1 binding, enabling immune escape.", "protein": "Spike protein (S) [SARS-CoV-2 Omicron]", "relationship_type": "causal", "source_pmcid": "PMC12354777" }, { "confidence": "low", "disease": "Autoimmune disease (potential cross-reactivity)", "glycan_involvement": "Glycosylation may influence cross-reactivity.", "mechanism": "3D1 shows weak autoreactivity in HEp-2 assay, suggesting possible cross-reactivity with self-antigens.", "protein": "Spike protein (S) [SARS-CoV-2]", "relationship_type": "biomarker", "source_pmcid": "PMC12354777" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "PTPRC is a heavily N-glycosylated glycoprotein; glycosylation is essential for its cell surface expression and function in immune signaling.", "mechanism": "Low PTPRC expression in LUAD correlates with poor prognosis and reduced immune cell infiltration.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation affects PTPRC's interactions with immune cells and its role in immune checkpoint pathways.", "mechanism": "PTPRC expression predicts response to immune checkpoint inhibitor (ICI) therapy; higher expression correlates with better response.", "protein": "PTPRC (CD45)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Serum detection relies on glycosylated forms of PTPRC.", "mechanism": "Serum PTPRC levels are reduced in LUAD patients and can distinguish LUAD from healthy controls (AUC=0.79).", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation is required for PTPRC's immune regulatory functions.", "mechanism": "High PTPRC expression is associated with increased immune cell infiltration (T cells, B cells, macrophages) and better prognosis.", "protein": "PTPRC (CD45)", "relationship_type": "protective", "source_pmcid": "PMC12354869" }, { "confidence": "medium", "disease": "Chronic lymphocytic leukemia (CLL)", "glycan_involvement": "Glycosylation modulates CD45 isoform expression and function.", "mechanism": "Decreased CD45 expression on CLL cells correlates with better overall survival.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "medium", "disease": "Multiple myeloma (MM)", "glycan_involvement": "Glycosylation affects CD45 surface expression and immune interactions.", "mechanism": "High CD45 expression on MM tumor cells is associated with good prognosis.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "medium", "disease": "Severe combined immunodeficiency", "glycan_involvement": "Glycosylation is essential for CD45 function and stability.", "mechanism": "Altered or deficient CD45 leads to severe combined immunodeficiency due to impaired T/B cell signaling.", "protein": "PTPRC (CD45)", "relationship_type": "causal", "source_pmcid": "PMC12354869" }, { "confidence": "low", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation may affect CD45-HIV-1 interactions.", "mechanism": "CD45 modulates HIV-1 gp120-induced apoptosis; deficiency reduces apoptosis, reconstitution increases it.", "protein": "PTPRC (CD45)", "relationship_type": "causal/modulatory", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation influences PTPRC's immune signaling and checkpoint regulation.", "mechanism": "PTPRC expression correlates with immune checkpoint (PD-1, PD-L1, CTLA-4) expression, indicating immune microenvironment status.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "Lung adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation is required for proper immune cell interactions.", "mechanism": "PTPRC expression is associated with infiltration of specific immune cell subsets (e.g., CD4+ memory T cells), impacting prognosis.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC12354869" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not directly addressed; G3BP1 may be glycosylated but glycan role not specified.", "mechanism": "Reduced hepatic G3BP1 levels correlate with MASLD severity; low G3BP1 is associated with increased lipid accumulation.", "protein": "G3BP1", "relationship_type": "biomarker", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Not directly addressed.", "mechanism": "G3BP1 levels are reduced in MASH; loss of G3BP1 exacerbates disease progression.", "protein": "G3BP1", "relationship_type": "biomarker", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not specified.", "mechanism": "Hepatic G3BP1 promotes autophagosome-lysosome fusion and lipid degradation; its loss worsens MASLD.", "protein": "G3BP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Not specified.", "mechanism": "G3BP1 facilitates autophagic lipid clearance; knockout increases steatosis and fibrosis.", "protein": "G3BP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Not specified.", "mechanism": "G3BP1 knockout in hepatocytes causes increased lipid accumulation and impaired autophagy.", "protein": "G3BP1", "relationship_type": "causal", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Not specified.", "mechanism": "G3BP1 knockout leads to increased liver fibrosis and inflammation.", "protein": "G3BP1", "relationship_type": "causal", "source_pmcid": "PMC12354899" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "STX17 is a glycoprotein; glycosylation may affect membrane localization but not discussed.", "mechanism": "STX17 interacts with G3BP1 to promote autophagosome-lysosome fusion; disruption impairs lipid clearance.", "protein": "STX17", "protein_enriched": { "function": "In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a r", "gene_name": "KRTAP4-7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYR0" }, "relationship_type": "protective", "source_pmcid": "PMC12354899" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "VAMP8 is a glycoprotein; glycosylation may affect function but not discussed.", "mechanism": "VAMP8 interacts with G3BP1 to facilitate autophagosome-lysosome fusion; loss of interaction impairs autophagy.", "protein": "VAMP8", "relationship_type": "protective", "source_pmcid": "PMC12354899" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not specified.", "mechanism": "G3BP1 is required for nuclear translocation of TFE3, which suppresses lipogenesis; loss of G3BP1 impairs TFE3 function.", "protein": "TFE3", "protein_enriched": { "function": "Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:2338243, PubMed:24448649, PubMed:29146937, PubMed:30733432, PubMed:31672913, PubMed:37079666). ", "gene_name": "TFE3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19532" }, "relationship_type": "protective", "source_pmcid": "PMC12354899" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not specified.", "mechanism": "G3BP1 knockout increases fibrogenic gene expression and fibrosis in MASH model.", "protein": "G3BP1", "relationship_type": "causal", "source_pmcid": "PMC12354899" }, { "confidence": "high", "disease": "Neuroblastoma", "glycan_involvement": "N-glycosylation required for proper cell surface expression and ADC binding.", "mechanism": "ALK is highly expressed on neuroblastoma cell surfaces; targeting with antibody-drug conjugates (ADCs) induces tumor cell death.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "high", "disease": "Fusion-positive rhabdomyosarcoma", "glycan_involvement": "N-glycosylation supports surface localization and antibody recognition.", "mechanism": "ALK is overexpressed on tumor cell surfaces; ADC targeting leads to tumor regression.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "high", "disease": "Colorectal carcinoma", "glycan_involvement": "N-glycosylation enables surface expression and ADC access.", "mechanism": "ALK is expressed in subsets of metastatic colorectal carcinoma; ADCs targeting ALK show efficacy in preclinical models.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Malignant melanoma", "glycan_involvement": "N-glycosylation likely required for surface targeting.", "mechanism": "ALK is overexpressed in subsets; potential for ADC-based therapy.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Ovarian carcinoma", "glycan_involvement": "N-glycosylation supports surface expression.", "mechanism": "ALK is expressed in subsets; may be targeted by ADCs.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Breast carcinoma", "glycan_involvement": "N-glycosylation supports surface expression.", "mechanism": "ALK is expressed in subsets; ADCs may be effective.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Ewing sarcoma", "glycan_involvement": "N-glycosylation supports detection by antibodies.", "mechanism": "ALK RNA is elevated in some cases; potential diagnostic marker.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "biomarker", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Dysembryoplastic neuroepithelial tumor", "glycan_involvement": "N-glycosylation supports antibody-based detection.", "mechanism": "ALK RNA is elevated; possible diagnostic utility.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "biomarker", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Ganglioglioma", "glycan_involvement": "N-glycosylation supports antibody-based detection.", "mechanism": "ALK RNA is elevated in some tumors.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "biomarker", "source_pmcid": "PMC12354906" }, { "confidence": "medium", "disease": "Glioblastoma multiforme", "glycan_involvement": "N-glycosylation supports antibody-based detection.", "mechanism": "ALK RNA is elevated in some tumors.", "protein": "Anaplastic Lymphoma Kinase (ALK)", "relationship_type": "biomarker", "source_pmcid": "PMC12354906" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "FGF21 levels are elevated in T2D, reflecting metabolic stress and FGF21 resistance.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "high", "disease": "Fragility fractures", "glycan_involvement": "Glycosylation may influence FGF21's bioactivity and half-life.", "mechanism": "Lower FGF21 levels in T2D are independently associated with increased risk of fragility fractures.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "medium", "disease": "Diabetic kidney disease", "glycan_involvement": "Not specified, but as a glycoprotein, glycosylation may affect function.", "mechanism": "FGF21 predicts progression of diabetic kidney disease in T2D.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Not specified.", "mechanism": "FGF21 levels predict cardiovascular complications in T2D.", "protein": "Fibroblast growth factor 21", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "medium", "disease": "Fragility fractures", "glycan_involvement": "Glycosylation may modulate FGF21's receptor interactions.", "mechanism": "FGF21 influences bone turnover by promoting osteoclastogenesis and inhibiting osteoblastogenesis; low FGF21 may impair compensatory mechanisms in T2D.", "protein": "Fibroblast growth factor 21", "relationship_type": "causal", "source_pmcid": "PMC12354919" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "FGFR1 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "FGFR1 expression is suppressed in T2D, contributing to FGF21 resistance.", "protein": "Fibroblast growth factor receptor 1", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "\u03b2-Klotho is a glycoprotein; glycosylation may affect receptor complex formation.", "mechanism": "\u03b2-Klotho expression is suppressed in T2D, contributing to FGF21 resistance.", "protein": "\u03b2-Klotho", "relationship_type": "biomarker", "source_pmcid": "PMC12354919" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "TIGIT is a glycoprotein; glycosylation may affect ligand binding and antibody recognition.", "mechanism": "TIGIT is an immune checkpoint receptor; blockade enhances anti-tumor T cell responses.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "IL-6RA is N-glycosylated, which can modulate receptor function and antibody binding.", "mechanism": "IL-6RA mediates pro-inflammatory signaling; blockade reduces inflammation.", "protein": "IL-6RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Complement-mediated diseases", "glycan_involvement": "C5aR is a glycoprotein; glycosylation may affect receptor conformation and antibody access.", "mechanism": "C5aR mediates inflammatory responses to complement activation; antagonism reduces tissue damage.", "protein": "C5aR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CXCR4 is glycosylated; glycosylation can influence ligand binding and antibody recognition.", "mechanism": "CXCR4 promotes tumor cell migration and metastasis; inhibition blocks tumor spread.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "TIM-3 is a glycoprotein; glycosylation may modulate ligand interactions.", "mechanism": "TIM-3 is an immune checkpoint; blockade can restore T cell function in tumors.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CTLA-4 is glycosylated; glycosylation can affect receptor stability and antibody binding.", "mechanism": "CTLA-4 inhibits T cell activation; blockade enhances anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "OX40 is a glycoprotein; glycosylation may influence receptor function.", "mechanism": "OX40 co-stimulates T cells; agonism can enhance anti-tumor responses.", "protein": "OX40", "protein_enriched": { "function": "Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity", "gene_name": "TNFRSF4", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P43489" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "N-glycosylation affects receptor function and antibody interaction.", "mechanism": "IL-6RA blockade reduces inflammation in various diseases.", "protein": "IL-6RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Infectious diseases (HIV, etc.)", "glycan_involvement": "Glycosylation modulates receptor-ligand interactions.", "mechanism": "CXCR4 is a co-receptor for HIV entry; blockade prevents infection.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "CD155 is a glycoprotein; glycosylation may affect immune recognition.", "mechanism": "CD155 is overexpressed in tumors and interacts with TIGIT to suppress immunity.", "protein": "CD155", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12355719" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "TGF\u03b21 is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "Elevated TGF\u03b21 promotes activation of hepatic stellate cells and ECM deposition, driving fibrosis.", "protein": "TGF\u03b21", "relationship_type": "causal", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "NAT10 modifies RNA, indirectly affecting glycoprotein expression.", "mechanism": "NAT10 catalyzes ac4C modification of TGF\u03b21 mRNA, increasing its stability and promoting fibrosis.", "protein": "NAT10", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "PTBP1 recognizes modified RNA, influencing glycoprotein production.", "mechanism": "PTBP1 binds ac4C-modified TGF\u03b21 mRNA, stabilizing it and enhancing TGF\u03b21-driven fibrosis.", "protein": "PTBP1", "protein_enriched": { "function": "Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine trac", "gene_name": "PTBP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P26599" }, "relationship_type": "causal", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "Cellular senescence", "glycan_involvement": "Glycosylation regulates TGF\u03b21 secretion.", "mechanism": "TGF\u03b21 secreted by senescent cells drives further senescence via ROS and ECM deposition.", "protein": "TGF\u03b21", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "Cellular senescence", "glycan_involvement": "Indirect via RNA modification of glycoprotein mRNAs.", "mechanism": "NAT10 upregulation increases ac4C RNA modification, promoting senescence.", "protein": "NAT10", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12355746" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Deacetylation of RNA may reduce glycoprotein-driven fibrosis.", "mechanism": "SIRT7 acts as an ac4C deacetylase, antagonizing NAT10 and reducing fibrosis.", "protein": "SIRT7", "protein_enriched": { "function": "NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase, deglutarylase and dedecanoylase), depending on the context (PubMed:22722849, PubM", "gene_name": "SIRT7", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRC8" }, "relationship_type": "protective", "source_pmcid": "PMC12355746" }, { "confidence": "medium", "disease": "Hutchinson-Gilford progeria syndrome (HGPS)", "glycan_involvement": "Indirect via RNA modification of glycoprotein mRNAs.", "mechanism": "NAT10 inhibition (Remodelin) ameliorates aging phenotypes in HGPS mice.", "protein": "NAT10", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12355746" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Indirect via RNA modification of glycoprotein mRNAs.", "mechanism": "NAT10 promotes cardiac fibrosis via TGF\u03b21 ac4C modification.", "protein": "NAT10", "relationship_type": "causal", "source_pmcid": "PMC12355746" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Indirect via RNA modification of glycoprotein mRNAs.", "mechanism": "NAT10 accelerates pulmonary fibrosis through TGF\u03b21 ac4C modification.", "protein": "NAT10", "relationship_type": "causal", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "\u03b1-SMA is a glycoprotein; glycosylation may affect its function.", "mechanism": "\u03b1-SMA is upregulated in activated hepatic stellate cells during fibrosis.", "protein": "\u03b1-SMA (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC12355746" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its stability and serum half-life, but not directly discussed.", "mechanism": "Elevated serum ALT is used as a screening and diagnostic biomarker for MASLD in children.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355774" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "AST is a glycoprotein; glycosylation may influence secretion and stability.", "mechanism": "Elevated AST is used alongside ALT to assess liver injury in MASLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355774" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "No direct glycosylation involvement discussed.", "mechanism": "PNPLA3 I148M variant increases risk for hepatic steatosis, steatohepatitis, fibrosis, and cirrhosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12355774" }, { "confidence": "high", "disease": "Steatohepatitis", "glycan_involvement": "No direct glycosylation involvement discussed.", "mechanism": "PNPLA3 I148M variant is associated with increased risk of steatohepatitis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12355774" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "No direct glycosylation involvement discussed.", "mechanism": "PNPLA3 I148M variant increases risk of liver fibrosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12355774" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "No direct glycosylation involvement discussed.", "mechanism": "PNPLA3 I148M variant increases risk of cirrhosis.", "protein": "PNPLA3", "protein_enriched": { "function": "Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and ", "gene_name": "PNPLA3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NST1" }, "relationship_type": "causal", "source_pmcid": "PMC12355774" }, { "confidence": "high", "disease": "RA-ILD", "glycan_involvement": "KL-6 is a heavily O-glycosylated mucin; glycosylation is essential for its secretion and biomarker function.", "mechanism": "KL-6 is released from injured type II alveolar epithelial cells, promotes fibroblast migration/proliferation, and inhibits fibroblast apoptosis, reflecting fibrotic lung injury.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "high", "disease": "RA-ILD", "glycan_involvement": "IL-6 is N-glycosylated, which affects its stability and secretion.", "mechanism": "IL-6 elevation reflects systemic inflammation and may drive Th17/Treg imbalance, contributing to lung fibrosis.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "high", "disease": "RA-ILD", "glycan_involvement": "Cytokeratin 19 is O-glycosylated; glycosylation may modulate its release during cell injury.", "mechanism": "CYFRA21-1 is released during epithelial cell injury, indicating ongoing lung epithelial damage.", "protein": "Cytokeratin 19 fragment (CYFRA21-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "medium", "disease": "RA-ILD", "glycan_involvement": "CA15-3 is a glycosylated epitope of MUC1; glycosylation is required for antigenicity and detection.", "mechanism": "CA15-3 (MUC1 epitope) elevation is associated with pulmonary fibrosis and epithelial injury.", "protein": "Carbohydrate Antigen 15-3 (CA15-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "high", "disease": "ILD", "glycan_involvement": "O-glycosylation of KL-6 is critical for its biomarker role.", "mechanism": "KL-6 elevation is independent of systemic inflammation, specifically marking fibrotic lung processes.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "medium", "disease": "RA-ILD", "glycan_involvement": "RF is an IgM glycoprotein; glycosylation affects antibody function and immune complex formation.", "mechanism": "Elevated RF levels are associated with increased risk of RA-ILD, reflecting autoimmune activity.", "protein": "Rheumatoid Factor (RF)", "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "medium", "disease": "RA-ILD", "glycan_involvement": "ACPA is an IgG glycoprotein; glycosylation modulates effector functions.", "mechanism": "Elevated ACPA is linked to increased risk of RA-ILD, especially with smoking, indicating autoimmune lung involvement.", "protein": "Anti-cyclic citrullinated peptide antibody (ACPA)", "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "high", "disease": "RA", "glycan_involvement": "N-glycosylation affects IL-6 receptor binding and pharmacokinetics.", "mechanism": "IL-6 drives systemic inflammation in RA and is a target for biologic therapies.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355783" }, { "confidence": "medium", "disease": "RA", "glycan_involvement": "O-glycosylation is essential for KL-6 detection.", "mechanism": "KL-6 may indicate subclinical lung involvement in RA patients.", "protein": "Krebs von den Lungen-6 (KL-6)", "protein_enriched": { "function": "Involved in cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. In", "gene_name": "CADM3", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G43223CG", "G68490OW", "G49108TO" ], "uniprot_id": "Q8N126" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "medium", "disease": "ILD", "glycan_involvement": "O-glycosylation may affect fragment release and detection.", "mechanism": "CYFRA21-1 reflects epithelial cell injury in various forms of ILD.", "protein": "Cytokeratin 19 fragment (CYFRA21-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12355783" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "CASP3 is glycosylated, which may affect its stability and activity in apoptosis.", "mechanism": "CASP3 is a key executor of apoptosis in pancreatic \u03b2-cells; inhibition reduces \u03b2-cell death.", "protein": "Caspase-3 (CASP3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355841" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "TNF is glycosylated, influencing secretion and receptor binding.", "mechanism": "TNF promotes inflammation and \u03b2-cell apoptosis; inhibition reduces inflammatory damage.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Diabetic Complications (macrovascular/microvascular)", "glycan_involvement": "MMP9 glycosylation affects enzyme activity and tissue localization.", "mechanism": "MMP9 is involved in tissue remodeling and vascular damage in diabetes.", "protein": "Matrix Metallopeptidase 9 (MMP9)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Pancreatic \u03b2-cell apoptosis", "glycan_involvement": "Bcl-2 glycosylation may regulate anti-apoptotic function.", "mechanism": "Bcl-2 inhibits apoptosis; upregulation protects \u03b2-cells from death.", "protein": "B-cell Lymphoma 2 (Bcl-2)", "relationship_type": "protective", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Pancreatic \u03b2-cell apoptosis", "glycan_involvement": "Bax glycosylation may affect pro-apoptotic activity.", "mechanism": "Bax promotes apoptosis; upregulation leads to \u03b2-cell loss.", "protein": "Bcl-2-associated X Protein (Bax)", "relationship_type": "causal", "source_pmcid": "PMC12355841" }, { "confidence": "high", "disease": "Pancreatic \u03b2-cell apoptosis", "glycan_involvement": "Glycosylation may modulate CASP3 activation.", "mechanism": "CASP3 activation directly induces \u03b2-cell apoptosis.", "protein": "Caspase-3 (CASP3)", "relationship_type": "causal", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Diabetic Complications (macrovascular/microvascular)", "glycan_involvement": "Glycosylation affects TNF stability and receptor interaction.", "mechanism": "TNF drives chronic inflammation, contributing to vascular complications.", "protein": "Tumor Necrosis Factor (TNF)", "relationship_type": "causal", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation modulates MMP9 activity.", "mechanism": "Elevated MMP9 correlates with tissue damage and disease progression.", "protein": "Matrix Metallopeptidase 9 (MMP9)", "relationship_type": "biomarker", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation may enhance Bcl-2 anti-apoptotic function.", "mechanism": "Bcl-2 upregulation by SCM-198 protects \u03b2-cells from apoptosis.", "protein": "B-cell Lymphoma 2 (Bcl-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355841" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Glycosylation may regulate Bax pro-apoptotic activity.", "mechanism": "Bax downregulation by SCM-198 reduces \u03b2-cell apoptosis.", "protein": "Bcl-2-associated X Protein (Bax)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355841" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Albumin is N-glycosylated, which affects its stability and transport functions.", "mechanism": "Low serum albumin (as part of ANLR) is associated with increased mortality in sepsis, reflecting poor nutritional status and impaired endothelial function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates albumin\u2019s antioxidant and transport properties.", "mechanism": "Higher albumin levels (high ANLR) protect against organ dysfunction by maintaining oncotic pressure, antioxidant transport, and vascular integrity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation status may influence therapeutic efficacy.", "mechanism": "Albumin supplementation may improve outcomes in sepsis patients with low ANLR by restoring vascular integrity and reducing edema.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Diabetic foot ulcer", "glycan_involvement": "Glycosylation may affect albumin\u2019s wound healing properties.", "mechanism": "Elevated ANLR (higher albumin) is linked to lower risk of diabetic foot ulcer development.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Coronary artery disease", "glycan_involvement": "Glycosylation impacts albumin\u2019s vascular protective functions.", "mechanism": "ANLR improves prediction of coronary artery disease risk, integrating albumin\u2019s nutritional and anti-inflammatory roles.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Altered glycosylation may worsen albumin loss and dysfunction.", "mechanism": "Loss of albumin during sepsis exacerbates oxidative stress, endothelial dysfunction, and microvascular thrombosis, driving organ failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12355847" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects albumin\u2019s stability and measurement accuracy.", "mechanism": "ANLR (albumin/NLR) is a superior prognostic biomarker for sepsis mortality compared to traditional markers.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may modulate immune interactions.", "mechanism": "Low ANLR reflects immune exhaustion and poor nutritional status, marking advanced sepsis-related dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation supports albumin\u2019s anti-inflammatory effects.", "mechanism": "High ANLR indicates balanced immune response and reduced inflammatory burden, mitigating organ dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12355847" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may influence albumin\u2019s therapeutic monitoring.", "mechanism": "ANLR can guide early nutritional and anti-inflammatory interventions in sepsis management.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12355847" }, { "confidence": "high", "disease": "ccRCC", "glycan_involvement": "AGE adducts (CML, CEL, pentosidine, pyrraline) on lysine residues, especially at drug-binding sites.", "mechanism": "AGE-modified albumin levels are lower in ccRCC tissue compared to non-tumor kidney, reflecting altered metabolism and uptake.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "AGE adducts on cysteine and arginine residues, affecting disulfide bond formation.", "mechanism": "AGE modifications (CEC/CMC, pentosidine, argpyrimidine) more abundant in ccRCC, may impair albumin maturation.", "protein": "Pre-proalbumin", "relationship_type": "biomarker", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "Carboxyethyl/carmoxymethyl-cysteine (CEC/CMC) modification.", "mechanism": "AGE modification at Cys-343 in catalytic domain may impair glycolytic flux, contributing to metabolic reprogramming.", "protein": "PFKP", "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "Pentosidine modification on lysine.", "mechanism": "AGE modification at K-238 (acetylation site) may disrupt enzyme activity and post-translational regulation.", "protein": "TPI1", "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "high", "disease": "ccRCC", "glycan_involvement": "Carboxyethyl-lysine (CEL) modification.", "mechanism": "AGE modification at K-186 near substrate binding and sumoylation site may impair glycolysis and nuclear functions.", "protein": "GAPDH", "protein_enriched": { "function": "Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde", "gene_name": "GAPDH", "glycan_count": 20, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G05528SJ", "G06356OH", "G11629QQ", "G14547CB", "G20706XG", "G27058EU", "G48414YA", "G56784JY", "G57888GL", "G63136LV", "G65344XH", "G68490OW", "G78787DI", "G90787TS", "G49108TO", "G22310AV", "G43669FQ", "G84452RH", "G70994MS" ], "uniprot_id": "P04406" }, "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "high", "disease": "ccRCC", "glycan_involvement": "Carboxymethyl-lysine (CML) and pentosidine modification.", "mechanism": "AGE modification at K-162 near substrate binding and c-myc repression domain may affect glycolysis and gene regulation.", "protein": "ENO1", "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "Carboxyethyl-cysteine (CEC) modification.", "mechanism": "AGE modification at Cys-49 in A domain may alter oligomerization and activity, promoting Warburg effect.", "protein": "PKM2", "protein_enriched": { "function": "Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:2084", "gene_name": "PKM", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14618" }, "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "Carboxymethyl-cysteine (CMC) modification.", "mechanism": "AGE modification at Cys-58 in SOD-Cu domain may inactivate antioxidant defense, increasing ROS.", "protein": "HEL-S-44 (Cu\u2013Zn SOD)", "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "medium", "disease": "ccRCC", "glycan_involvement": "Carboxyethyl-cysteine (CEC) modification.", "mechanism": "AGE modification at Cys-366 in client-binding domain may disrupt chaperone function and cell cycle regulation.", "protein": "HSP90AB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12355867" }, { "confidence": "low", "disease": "ccRCC", "glycan_involvement": "Pyrraline modification on lysine.", "mechanism": "AGE modification at K-128/K-137 in DNA-binding domain may impair transcriptional regulation.", "protein": "SHOX2", "protein_enriched": { "function": "Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. May promote the assembly of presynaptic RA", "gene_name": "RAD51B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15315" }, "relationship_type": "causal", "source_pmcid": "PMC12355867" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "O-glycosylation critical for gel-forming properties and mucus viscosity.", "mechanism": "Elevated MUC5AC levels contribute to increased sputum viscosity and impaired mucociliary clearance.", "protein": "Mucin 5AC (MUC5AC)", "protein_enriched": { "function": "Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a p", "gene_name": "STAB2", "glycan_count": 6, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G49108TO", "G01650EU", "G27058EU", "G28541PG", "G45504EY", "G63041LO" ], "uniprot_id": "Q8WWQ8" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "O-glycosylation essential for mucin polymerization and mucus structure.", "mechanism": "High MUC5B levels increase sputum solids and elasticity, promoting airway obstruction.", "protein": "Mucin 5B (MUC5B)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12355870" }, { "confidence": "medium", "disease": "Bronchiectasis", "glycan_involvement": "O-glycosylation affects mucin barrier function.", "mechanism": "Altered MUC2 levels reflect changes in mucus composition and airway inflammation.", "protein": "Mucin 2 (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC12355870" }, { "confidence": "medium", "disease": "Bronchiectasis", "glycan_involvement": "Extensive O-glycosylation influences mucin interaction with pathogens.", "mechanism": "MUC4 may modulate epithelial protection and mucus properties in bronchiectasis.", "protein": "Mucin 4 (MUC4)", "relationship_type": "biomarker", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "Glycosylation may affect NE stability and activity.", "mechanism": "NE drives neutrophilic inflammation, increases sputum purulence, and stimulates mucin production.", "protein": "Neutrophil Elastase (NE)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "Glycosylation modulates cytokine-receptor interactions.", "mechanism": "IL-8 promotes neutrophil influx, airway obstruction, and tissue damage.", "protein": "Interleukin-8 (IL-8)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "Glycosylation influences cytokine stability and secretion.", "mechanism": "IL-1\u03b2 impairs mucociliary function and promotes airway neutrophilia.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Bronchiectasis", "glycan_involvement": "Glycosylation affects TNF-\u03b1 bioactivity.", "mechanism": "TNF-\u03b1 is linked to inflammation, poorer lung function, and structural injury.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Airway mucus hypersecretion", "glycan_involvement": "O-glycosylation determines mucus gel formation and secretion.", "mechanism": "Overexpression of MUC5AC leads to excessive mucus production and airway obstruction.", "protein": "Mucin 5AC (MUC5AC)", "protein_enriched": { "function": "Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a p", "gene_name": "STAB2", "glycan_count": 6, "glycosylation_sites_count": 28, "glytoucan_ids": [ "G49108TO", "G01650EU", "G27058EU", "G28541PG", "G45504EY", "G63041LO" ], "uniprot_id": "Q8WWQ8" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12355870" }, { "confidence": "medium", "disease": "Acute exacerbation of bronchiectasis", "glycan_involvement": "O-glycosylation modulates mucin function during inflammation.", "mechanism": "Elevated MUC5B levels are associated with increased risk of exacerbations.", "protein": "Mucin 5B (MUC5B)", "relationship_type": "biomarker", "source_pmcid": "PMC12355870" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect p62 stability and autophagic flux.", "mechanism": "Impaired p62-mediated autophagy leads to accumulation of protein aggregates, a hallmark of AD.", "protein": "SQSTM1 (p62)", "relationship_type": "causal", "source_pmcid": "PMC12356038" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may regulate p62 interactions with ubiquitinated proteins.", "mechanism": "Defective p62-autophagy system contributes to neurodegeneration in PD.", "protein": "SQSTM1 (p62)", "relationship_type": "causal", "source_pmcid": "PMC12356038" }, { "confidence": "high", "disease": "Age-related neurodegeneration", "glycan_involvement": "Glycosylation may modulate NQO1 activity and stability.", "mechanism": "NQO1 upregulation via Nrf2 activation enhances antioxidant defense, reducing neurodegeneration.", "protein": "NQO1", "protein_enriched": { "function": "Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons ar", "gene_name": "NQO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15559" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury", "glycan_involvement": "Glycosylation may influence HMOX1 localization and function.", "mechanism": "HMOX1 induction protects neurons from oxidative damage during ischemia-reperfusion.", "protein": "HMOX1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "HMOX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09601" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation may affect proteasome assembly and activity.", "mechanism": "PSMA6 inhibition leads to proteasome dysfunction, contributing to diabetic nephropathy.", "protein": "PSMA6", "protein_enriched": { "function": "Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with dif", "gene_name": "PSMA6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60900" }, "relationship_type": "causal", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may regulate ribosomal protein function.", "mechanism": "RPS23 is associated with neurofibrillary tangle formation in AD.", "protein": "RPS23", "protein_enriched": { "function": "Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:28257692). The small ribos", "gene_name": "RPS23", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59324HL", "G49108TO" ], "uniprot_id": "P62266" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may modulate autophagy and cell death pathways.", "mechanism": "Low GABARAPL1 expression decreases sensitivity to ferroptosis in cancer stem cells.", "protein": "GABARAPL1", "protein_enriched": { "function": "Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor (PubMed:16431922). Involved in f", "gene_name": "GABARAPL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H0R8" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Age-related neurodegeneration", "glycan_involvement": "Glycosylation may affect transporter function and cell surface expression.", "mechanism": "SLC7A11 upregulation enhances cystine uptake, supporting glutathione synthesis and antioxidant defense.", "protein": "SLC7A11", "protein_enriched": { "function": "Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847", "gene_name": "SLC7A11", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UPY5" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "medium", "disease": "Premature aging", "glycan_involvement": "Glycosylation may regulate enzyme activity.", "mechanism": "TXNRD1 supports redox homeostasis, mitigating aging-related oxidative stress.", "protein": "TXNRD1", "protein_enriched": { "function": "Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form (PubMed:8577704). Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation.", "gene_name": "TXNRD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16881" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "low", "disease": "LPS-induced hepatitis", "glycan_involvement": "Glycosylation may influence protein stability and signaling.", "mechanism": "OSGIN1 activation limits oxidative stress and inflammation in hepatitis.", "protein": "OSGIN1", "protein_enriched": { "function": "Involved in membrane protein trafficking at the base of the ciliary organelle. Mediates recruitment onto plasma membrane of the BBSome complex which would constitute a coat complex required for sortin", "gene_name": "ARL6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H0F7" }, "relationship_type": "protective", "source_pmcid": "PMC12356038" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "LAM is a heavily glycosylated glycolipid; antibody recognition depends on glycan structure.", "mechanism": "LAM is a major Mtb surface antigen; antibodies to LAM are induced by infection and vaccination and can mediate protection.", "protein": "Lipoarabinomannan (LAM)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12356069" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "AM is a polysaccharide; glycan epitopes are critical for immune recognition.", "mechanism": "AM-specific antibodies are detected across infection stages and can mediate protection.", "protein": "Arabinomannan (AM)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation may affect antigenicity and antibody binding.", "mechanism": "Monoclonal antibodies to PstS1 reduce lung bacterial load in mice.", "protein": "PstS1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Antibodies to LpqH reduce Mtb burden in animal models.", "protein": "LpqH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "N-glycosylation regulates ICAM-1 function and cell-cell interactions.", "mechanism": "ICAM-1 upregulation on fibroblasts in iBALT enhances lymphocyte adhesion and organization, supporting local immunity.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "N-glycosylation modulates VCAM-1 adhesive properties.", "mechanism": "VCAM-1 upregulation in iBALT supports lymphocyte retention and immune structure formation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "PNAd function depends on specific glycan modifications (sialylation, sulfation).", "mechanism": "PNAd expression on HEVs in iBALT facilitates lymphocyte homing to inflamed lung tissue.", "protein": "PNAd", "relationship_type": "causal/protective", "source_pmcid": "PMC12356069" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation affects PD-L1 stability and immune checkpoint function.", "mechanism": "PD-L1 on B cells and other cells regulates Tfh positioning and T cell activation in iBALT.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "regulatory", "source_pmcid": "PMC12356069" }, { "confidence": "low", "disease": "Tuberculosis", "glycan_involvement": "N-glycosylation is essential for PECAM-1 adhesive function.", "mechanism": "PECAM-1 on lymphatic endothelium mediates leukocyte transmigration during lung inflammation.", "protein": "PECAM-1", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for eff", "gene_name": "Pecam1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G25079LO", "G24748EV", "G15664MX", "G72747WU", "G31986NC", "G80920RR", "G49108TO" ], "uniprot_id": "Q08481" }, "relationship_type": "causal", "source_pmcid": "PMC12356069" }, { "confidence": "low", "disease": "Tuberculosis", "glycan_involvement": "Glycosylation modulates CD99-mediated adhesion.", "mechanism": "CD99 on endothelial cells facilitates immune cell transmigration into inflamed lung tissue.", "protein": "CD99", "protein_enriched": { "function": "Involved in T-cell adhesion processes and in spontaneous rosette formation with erythrocytes. Plays a role in a late step of leukocyte extravasation helping leukocytes to overcome the endothelial base", "gene_name": "CD99", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO" ], "uniprot_id": "P14209" }, "relationship_type": "causal", "source_pmcid": "PMC12356069" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "SSA/Ro antigens are glycoproteins; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Diagnostic marker; associated with younger age, increased hematological abnormalities, and heightened B cell/T cell activation.", "protein": "Anti-SSA/Ro antibody (Ro60/Ro52)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "CENP-B is a glycoprotein; glycosylation may modulate autoantibody binding.", "mechanism": "Defines older pSS subgroup with increased Raynaud\u2019s phenomenon, cardiovascular dysfunction, and risk of PBC.", "protein": "Anti-centromere antibody (CENP-B)", "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Raynaud\u2019s phenomenon", "glycan_involvement": "Glycosylation may influence antigen presentation and immune complex formation.", "mechanism": "ACA positivity strongly associated with microvascular dysfunction and Raynaud\u2019s in pSS.", "protein": "Anti-centromere antibody (CENP-B)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "medium", "disease": "Left ventricular diastolic dysfunction", "glycan_involvement": "Glycosylation may affect immune-mediated tissue damage.", "mechanism": "ACA-positive pSS patients have increased cardiac involvement.", "protein": "Anti-centromere antibody (CENP-B)", "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "M2 antigen is a glycoprotein; glycosylation may affect autoantibody recognition.", "mechanism": "AMA-M2 positivity (especially in ACA-positive pSS) indicates increased risk for PBC.", "protein": "Anti-mitochondrial M2 antibody (AMA-M2)", "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "RF is an IgM/IgG glycoprotein; glycosylation modulates immune complex formation.", "mechanism": "RF is elevated in SSA-positive pSS, indicating overlap with RA.", "protein": "Rheumatoid factor (RF)", "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "IgG glycosylation affects effector function and immune regulation.", "mechanism": "Elevated in SSA-positive pSS; correlates with CD4+ T cell activation and disease severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "medium", "disease": "Primary biliary cholangitis (PBC)", "glycan_involvement": "IgM glycosylation influences complement activation and immune response.", "mechanism": "Elevated IgM in ACA-positive pSS is linked to increased risk of PBC.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "CD19 is a glycoprotein; glycosylation modulates B cell signaling.", "mechanism": "Increased CD19+ B cells in SSA-positive pSS drive autoantibody production and disease activity.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "medium", "disease": "Malignancy (tumor incidence)", "glycan_involvement": "NK cell markers are glycoproteins; glycosylation affects cytotoxic function.", "mechanism": "Reduced NK cell counts in pSS may impair tumor surveillance, increasing malignancy risk.", "protein": "CD16+CD56+ NK cell marker", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12356515" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Fibronectin is highly glycosylated; altered glycosylation may affect matrix assembly and cell signaling.", "mechanism": "Excess accumulation of fibronectin in liver cells contributes to extracellular matrix deposition and fibrosis.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12356863" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Platelet surface glycoproteins mediate interactions with liver sinusoidal cells; glycosylation affects function.", "mechanism": "Platelet count is used in fibrosis indices (MAF-5, FIB-4) to assess fibrosis risk.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "AST is glycosylated; glycan changes may influence serum stability and clearance.", "mechanism": "Elevated AST is a marker of liver injury and is included in fibrosis scoring algorithms.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "ALT glycosylation may affect enzyme activity and serum half-life.", "mechanism": "ALT levels are used in FIB-4 index for fibrosis risk assessment.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "VEGF glycosylation modulates receptor binding and angiogenic signaling.", "mechanism": "APs exposure induces VEGF resistance, contributing to vascular dysfunction and fibrosis.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Insulin resistance", "glycan_involvement": "Insulin receptor glycosylation is critical for cell surface expression and signaling.", "mechanism": "APs exposure induces insulin resistance, promoting metabolic dysfunction and fibrosis.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects HDL function and anti-inflammatory properties.", "mechanism": "Low HDL is a risk factor for MASLD and fibrosis; HDL glycoproteins modulate lipid transport.", "protein": "HDL-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "LDL levels are associated with MASLD risk; LDL glycoproteins influence lipid uptake and inflammation.", "protein": "LDL-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Altered glycosylation can impact albumin half-life and binding properties.", "mechanism": "Serum albumin is reduced in advanced fibrosis; glycosylation may affect stability.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356863" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Potential glycosylation of pathway components may regulate mitochondrial targeting and degradation.", "mechanism": "APs activate ROS-mediated PINK1/Parkin signaling in hepatic stellate cells, promoting mitophagy and fibrosis.", "protein": "PINK1/Parkin pathway proteins", "relationship_type": "causal", "source_pmcid": "PMC12356863" }, { "confidence": "high", "disease": "Congestive Heart Failure", "glycan_involvement": "Albumin is N-glycosylated; glycosylation affects stability and half-life.", "mechanism": "Low serum albumin reflects malnutrition, hepatic dysfunction, and systemic inflammation, correlating with poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "medium", "disease": "Septic Shock", "glycan_involvement": "Glycosylation modulates albumin's vascular and immune functions.", "mechanism": "Decreased albumin indicates increased vascular permeability and inflammation in sepsis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "medium", "disease": "Cardiorenal Syndrome", "glycan_involvement": "Altered glycosylation may affect albumin's transport and anti-inflammatory properties.", "mechanism": "Hypoalbuminemia exacerbates pulmonary congestion and progression of heart failure with renal involvement.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "medium", "disease": "Community-acquired Pneumonia", "glycan_involvement": "Glycosylation status may influence immune response.", "mechanism": "Low albumin is associated with increased severity and mortality risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "low", "disease": "Idiopathic Pulmonary Hypertension", "glycan_involvement": "Glycosylation may affect albumin's interaction with vascular endothelium.", "mechanism": "High albumin levels indicate myocardial fibrosis and poor prognosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "low", "disease": "Gastrointestinal Bleeding in Elderly", "glycan_involvement": "Glycosylation may affect albumin's stability during acute illness.", "mechanism": "BAR (BUN/Albumin ratio) predicts risk and severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "low", "disease": "Febrile Urinary Tract Infection in Infants", "glycan_involvement": "Not specified.", "mechanism": "BAR is predictive of severity.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "medium", "disease": "Congestive Heart Failure", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Elevated BAR correlates with increased IL-6, indicating inflammatory burden.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "medium", "disease": "Congestive Heart Failure", "glycan_involvement": "TNF-\u03b1 glycosylation modulates activity and stability.", "mechanism": "Elevated BAR correlates with increased TNF-\u03b1, reflecting inflammation and endothelial dysfunction.", "protein": "Tumor Necrosis Factor-alpha (TNF-\u03b1)", "relationship_type": "biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "low", "disease": "COPD", "glycan_involvement": "Not specified.", "mechanism": "BAR helps distinguish heart failure from COPD/asthma.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12356899" }, { "confidence": "high", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Glycosylation of gE is essential for its immunogenicity and proper folding.", "mechanism": "gE is the major target antigen for subunit vaccines that elicit protective T-cell and antibody responses against VZV reactivation.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356908" }, { "confidence": "high", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Fc region glycosylation facilitates Fc\u03b3R engagement and immune activation.", "mechanism": "Fusion of gE to human Fc enhances antigen uptake via Fc\u03b3 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virus infection", "glycan_involvement": "Glycosylation is critical for gE function and viral pathogenesis.", "mechanism": "gE is essential for VZV infectivity and cell-to-cell spread.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC12356908" }, { "confidence": "high", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Glycosylation of Fc and gE domains supports immunogenicity and Fc\u03b3R-mediated effects.", "mechanism": "LZ901 vaccine induces robust CD4+ and CD8+ T-cell responses, conferring protection against HZ.", "protein": "Recombinant gE-Fc fusion protein", "relationship_type": "protective", "source_pmcid": "PMC12356908" }, { "confidence": "medium", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "Anti-gE antibody titers serve as a biomarker for vaccine-induced immunity.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "biomarker", "source_pmcid": "PMC12356908" }, { "confidence": "medium", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Glycosylation influences Fc\u03b3R binding and immune readouts.", "mechanism": "Cellular immune responses to gE-Fc (CD4+/CD8+ T-cell cytokine production) indicate vaccine efficacy.", "protein": "Recombinant gE-Fc fusion protein", "relationship_type": "biomarker", "source_pmcid": "PMC12356908" }, { "confidence": "medium", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Fc glycosylation modulates immune activation and reactogenicity.", "mechanism": "Fc fusion enhances vaccine safety and immunogenicity compared to non-fused gE.", "protein": "Human IgG1 Fc fragment", "relationship_type": "protective", "source_pmcid": "PMC12356908" }, { "confidence": "high", "disease": "Herpes zoster (HZ)", "glycan_involvement": "Glycosylation is necessary for vaccine antigen structure and function.", "mechanism": "gE is the antigen in both HZ/su and LZ901 vaccines, targeted for immune protection.", "protein": "Varicella-zoster virus glycoprotein E (gE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356908" }, { "confidence": "high", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "Sialylation and O-glycosylation of PSGL-1 are required for EV-A71 binding.", "mechanism": "Facilitates EV-A71 viral entry as an attachment receptor.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "high", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "Glycosylation status affects receptor function and viral interaction.", "mechanism": "Primary uncoating receptor for EV-A71, mediates viral entry and infection.", "protein": "SCARB2", "protein_enriched": { "function": "Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting", "gene_name": "SCARB2", "glycan_count": 116, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G01521EA", "G05962QB", "G09831WQ", "G10773YW", "G11314AS", "G11870QZ", "G12313PD", "G16125XL", "G20210JR", "G23294PN", "G23984SE", "G25451PN", "G26377UA", "G30221QT", "G31309XD", "G32788FZ", "G35541EV", "G37818NZ", "G39471UU", "G42124LM", "G45395BF", "G47644PP", "G55132BD", "G60177UT", "G62894KT", "G65344XH", "G65414LI", "G67113SI", "G67164EE", "G68490OW", "G71051TA", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G82463GQ", "G82830MN", "G85269DF", "G87123QX", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94831VI", "G95046LV", "G95865ZB", "G09724ZC", "G11101UV", "G31852PQ", "G49755GI", "G52890YB", "G57489SP", "G69521XL", "G71463BG", "G76915KR", "G78811TO", "G98129XB", "G46071XJ", "G14260UH", "G15664MX", "G20425TQ", "G36442WJ", "G46503DX", "G46902YN", "G49018RC", "G49642SA", "G54010QB", "G56307ZW", "G60033FS", "G62765YT", "G64527OM", "G66621EA", "G70101JE", "G72747WU", "G83460ZZ", "G06583FZ", "G20312EM", "G44215PV", "G47012YE", "G77582RK", "G80223IX", "G81315DD", "G83229XP", "G22573RC", "G22768VO", "G37135JQ", "G46524LG", "G60230HH", "G83390WW", "G89864BN", "G00912UN", "G06247RL", "G08293MJ", "G10133VD", "G10846ZT", "G11629QQ", "G22310AV", "G27126ED", "G29526EI", "G31028YV", "G46691LC", "G47518TP", "G48414YA", "G58087IP", "G61751GZ", "G84452RH", "G85144OK", "G85554PZ", "G88374WZ", "G94470IW", "G96430BV", "G49108TO", "G06702MJ", "G06356OH", "G86795LJ", "G95133RI" ], "uniprot_id": "Q14108" }, "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "medium", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "Heparan sulfate glycosaminoglycan chains mediate virus binding.", "mechanism": "Serve as secondary attachment receptors for EV-A71, enhancing infectivity.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "low", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "Potential glycosylation may modulate receptor activity.", "mechanism": "Facilitates EV-A71 infection as a co-receptor.", "protein": "Annexin II (Anx2)", "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "medium", "disease": "Aseptic meningitis", "glycan_involvement": "Sialylated O-glycans required for neurotropic viral binding.", "mechanism": "Promotes EV-A71 neuroinvasion via glycan-mediated viral entry.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "medium", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "Glycans on SIgA J-chain mediate non-canonical antigen binding.", "mechanism": "SIgA neutralizes EV-A71 at mucosal surfaces, limiting infection.", "protein": "Secretory IgA (SIgA)", "relationship_type": "protective", "source_pmcid": "PMC12356949" }, { "confidence": "low", "disease": "Hand, foot, and mouth disease (HFMD)", "glycan_involvement": "C1q glycosylation modulates immune complex formation and cell entry.", "mechanism": "Complement-dependent antibody-dependent enhancement (ADE) may facilitate EV-A71 entry via C1qR.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal (ADE)", "source_pmcid": "PMC12356949" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation may affect neural tropism.", "mechanism": "SCARB2-mediated EV-A71 entry into neural cells contributes to CNS disease.", "protein": "SCARB2", "protein_enriched": { "function": "Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting", "gene_name": "SCARB2", "glycan_count": 116, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G01521EA", "G05962QB", "G09831WQ", "G10773YW", "G11314AS", "G11870QZ", "G12313PD", "G16125XL", "G20210JR", "G23294PN", "G23984SE", "G25451PN", "G26377UA", "G30221QT", "G31309XD", "G32788FZ", "G35541EV", "G37818NZ", "G39471UU", "G42124LM", "G45395BF", "G47644PP", "G55132BD", "G60177UT", "G62894KT", "G65344XH", "G65414LI", "G67113SI", "G67164EE", "G68490OW", "G71051TA", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G82463GQ", "G82830MN", "G85269DF", "G87123QX", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94831VI", "G95046LV", "G95865ZB", "G09724ZC", "G11101UV", "G31852PQ", "G49755GI", "G52890YB", "G57489SP", "G69521XL", "G71463BG", "G76915KR", "G78811TO", "G98129XB", "G46071XJ", "G14260UH", "G15664MX", "G20425TQ", "G36442WJ", "G46503DX", "G46902YN", "G49018RC", "G49642SA", "G54010QB", "G56307ZW", "G60033FS", "G62765YT", "G64527OM", "G66621EA", "G70101JE", "G72747WU", "G83460ZZ", "G06583FZ", "G20312EM", "G44215PV", "G47012YE", "G77582RK", "G80223IX", "G81315DD", "G83229XP", "G22573RC", "G22768VO", "G37135JQ", "G46524LG", "G60230HH", "G83390WW", "G89864BN", "G00912UN", "G06247RL", "G08293MJ", "G10133VD", "G10846ZT", "G11629QQ", "G22310AV", "G27126ED", "G29526EI", "G31028YV", "G46691LC", "G47518TP", "G48414YA", "G58087IP", "G61751GZ", "G84452RH", "G85144OK", "G85554PZ", "G88374WZ", "G94470IW", "G96430BV", "G49108TO", "G06702MJ", "G06356OH", "G86795LJ", "G95133RI" ], "uniprot_id": "Q14108" }, "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "low", "disease": "Myocarditis", "glycan_involvement": "Heparan sulfate chains required for viral attachment.", "mechanism": "Facilitate EV-A71 and coxsackievirus entry into cardiac tissue.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12356949" }, { "confidence": "low", "disease": "Acute flaccid myelitis", "glycan_involvement": "J-chain glycans facilitate mucosal immune exclusion.", "mechanism": "SIgA may limit neuroinvasion by neutralizing EV-A71 at mucosal entry points.", "protein": "Secretory IgA (SIgA)", "relationship_type": "protective", "source_pmcid": "PMC12356949" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "N-glycosylation is required for SLC1A5 plasma membrane localization and transporter function.", "mechanism": "Androgen-driven upregulation and N-glycosylation of SLC1A5 increases glutamine uptake in granulosa cells, leading to metabolic reprogramming and PCOS-like phenotypes.", "protein": "SLC1A5", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "N-glycosylation enhances SLC1A5 function, contributing to infertility phenotype.", "mechanism": "SLC1A5 overexpression in mouse ovaries impairs follicle development and reduces fertility index.", "protein": "SLC1A5", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "N-glycosylation increases SLC1A5 activity, impacting metabolic pathways.", "mechanism": "SLC1A5-mediated glutamine uptake alters energy metabolism and redox homeostasis, contributing to metabolic dysfunction in PCOS.", "protein": "SLC1A5", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Targeting glycosylated SLC1A5 may improve therapeutic efficacy.", "mechanism": "Pharmacological inhibition of SLC1A5 (GPNA) alleviates reproductive and metabolic symptoms in PCOS-like mice.", "protein": "SLC1A5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12356975" }, { "confidence": "medium", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Not specified.", "mechanism": "SLC1A5-driven glutamine metabolism increases \u03b1-KG, upregulating HDAC5, which suppresses histone acetylation and downregulates folliculogenesis genes.", "protein": "HDAC5", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Not specified.", "mechanism": "HDAC5-mediated histone hypoacetylation (H3K14ac, H3K56ac) represses CYP19A1, reducing aromatase activity and exacerbating androgen excess.", "protein": "CYP19A1", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "N-glycosylation status can be used as a biomarker for SLC1A5 activity.", "mechanism": "Elevated SLC1A5 expression and N-glycosylation in granulosa cells correlate with hyperandrogenic PCOS.", "protein": "SLC1A5", "relationship_type": "biomarker", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "N-glycosylation is essential for SLC1A5 function in disease.", "mechanism": "Androgen receptor (AR) directly binds SLC1A5 promoter, increasing its transcription and N-glycosylation, driving PCOS pathology.", "protein": "SLC1A5", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "Polycystic Ovary Syndrome (PCOS)", "glycan_involvement": "Inhibiting glycosylated SLC1A5 is protective.", "mechanism": "Inhibition of SLC1A5 restores estrous cycles, reduces cystic follicles, and improves metabolic parameters in PCOS-like mice.", "protein": "SLC1A5", "relationship_type": "protective", "source_pmcid": "PMC12356975" }, { "confidence": "medium", "disease": "Infertility", "glycan_involvement": "Not specified.", "mechanism": "Epigenetic repression of CYP19A1 by HDAC5 leads to reduced estrogen synthesis, contributing to infertility in PCOS.", "protein": "CYP19A1", "relationship_type": "causal", "source_pmcid": "PMC12356975" }, { "confidence": "high", "disease": "High-grade glioma (HGG)", "glycan_involvement": "LAT1 functions as a heterodimer with glycosylated 4F2hc/CD98 heavy chain, required for membrane localization.", "mechanism": "Increased endothelial LAT1 expression correlates with glioma grade and may support tumor proliferation.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "Glycosylation of 4F2hc/CD98 is essential for LAT1 function and trafficking.", "mechanism": "Endothelial LAT1 expression is increased in LGG compared to normal tissue, correlating with tumor grade.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation of 4F2hc/CD98 is required for LAT1 surface expression.", "mechanism": "LAT1 overexpression associated with poor survival and angiogenesis; targetable for imaging and drug delivery.", "protein": "LAT1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12360917" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation of 4F2hc/CD98 enables LAT1 membrane localization.", "mechanism": "LAT1 is highly expressed and used as a PET imaging target.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation of 4F2hc/CD98 is necessary for LAT1 function.", "mechanism": "LAT1 overexpression correlates with poor survival.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "Glycosylation of 4F2hc/CD98 enables LAT1 membrane localization.", "mechanism": "LAT1 is highly expressed and used as a PET imaging target.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "high", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "No direct glycosylation involvement reported for ASCT2.", "mechanism": "High ASCT2 mRNA expression correlates with worse survival in LGG.", "protein": "ASCT2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12360917" }, { "confidence": "high", "disease": "High-grade glioma (HGG)", "glycan_involvement": "No direct glycosylation involvement reported for ASCT2.", "mechanism": "Endothelial ASCT2 expression increases with glioma grade.", "protein": "ASCT2", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "No direct glycosylation involvement reported for ASCT2.", "mechanism": "High ASCT2 expression linked to poor survival.", "protein": "ASCT2", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "No direct glycosylation involvement reported for ASCT2.", "mechanism": "High ASCT2 expression linked to poor survival.", "protein": "ASCT2", "relationship_type": "biomarker", "source_pmcid": "PMC12360917" }, { "confidence": "high", "disease": "Symptomatic urinary tract infection (UTI)", "glycan_involvement": "CRP is a glycoprotein; its glycosylation affects stability and clearance.", "mechanism": "CRP is elevated in symptomatic UTI, reflecting systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "high", "disease": "Asymptomatic bacteriuria (ASB)", "glycan_involvement": "Glycosylation status may influence CRP's immune recognition.", "mechanism": "CRP is lower in ASB, indicating absence of systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "medium", "disease": "Symptomatic urinary tract infection (UTI)", "glycan_involvement": "GGT is a glycoprotein; glycosylation is important for its enzymatic activity.", "mechanism": "GGT is elevated in symptomatic UTI, possibly reflecting liver involvement or drug-induced injury.", "protein": "Gamma-glutamyl transpeptidase", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "medium", "disease": "Symptomatic urinary tract infection (UTI)", "glycan_involvement": "ALT is not a glycoprotein; no glycan involvement.", "mechanism": "ALT is elevated in symptomatic UTI, possibly due to infection or drug-induced liver injury.", "protein": "Alanine aminotransferase", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "low", "disease": "Asymptomatic bacteriuria (ASB)", "glycan_involvement": "Eosinophil granule proteins are glycosylated, which may affect immune modulation.", "mechanism": "Higher eosinophil percentage is associated with ASB; mechanism unclear.", "protein": "Eosinophil granule proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "medium", "disease": "Asymptomatic bacteriuria (ASB)", "glycan_involvement": "UPEC surface glycoproteins (e.g., adhesins) mediate colonization; glycosylation affects host-pathogen interaction.", "mechanism": "High bacterial counts in urine without inflammation indicate ASB.", "protein": "Bacterial particles (UPEC surface glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12361136" }, { "confidence": "medium", "disease": "Symptomatic urinary tract infection (UTI)", "glycan_involvement": "Bacterial glycoprotein glycans modulate immune evasion and adhesion.", "mechanism": "UPEC glycoproteins contribute to infection and immune activation.", "protein": "Bacterial particles (UPEC surface glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC12361136" }, { "confidence": "high", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "Glycosylation is essential for TROP2 membrane localization and function as a target.", "mechanism": "TROP2 is highly expressed in OSCC and can be targeted by antibody\u2013drug conjugates (ADCs) such as sacituzumab govitecan.", "protein": "TROP2", "protein_enriched": { "function": "May be involved in transcriptional regulation", "gene_name": "ZNF101", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZC7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "Glycosylation may affect antibody binding and detection.", "mechanism": "TROP2 overexpression is nearly universal in OSCC, making it a potential diagnostic and predictive biomarker.", "protein": "TROP2", "protein_enriched": { "function": "May be involved in transcriptional regulation", "gene_name": "ZNF101", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZC7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation required for ADC recognition.", "mechanism": "TROP2 is targeted by sacituzumab govitecan, approved for metastatic triple-negative breast cancer.", "protein": "TROP2", "protein_enriched": { "function": "May be involved in transcriptional regulation", "gene_name": "ZNF101", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZC7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "N-glycosylation is important for cell surface expression and ADC targeting.", "mechanism": "Nectin-4 is expressed in a subset of OSCC, especially HPV-positive cases, and is targetable by enfortumab vedotin.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "HPV-positive OSCC", "glycan_involvement": "Glycosylation may modulate cell adhesion and immune interactions.", "mechanism": "Nectin-4 expression is significantly higher in HPV-positive OSCC and may be induced by HPV oncoproteins E6/E7.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "Urothelial carcinoma", "glycan_involvement": "Glycosylation required for ADC binding.", "mechanism": "Nectin-4 is targeted by enfortumab vedotin, approved for advanced urothelial carcinoma.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12361728" }, { "confidence": "medium", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "Nectin-4 expression is associated with improved overall survival in univariate analysis, possibly due to its association with HPV positivity.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "protective", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "Not applicable due to lack of expression.", "mechanism": "Claudin 18.2 is not expressed in OSCC, thus not a useful biomarker or therapeutic target for this disease.", "protein": "Claudin 18.2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12361728" }, { "confidence": "medium", "disease": "HPV-positive OSCC", "glycan_involvement": "Glycosylation status may be altered by HPV-induced epigenetic changes.", "mechanism": "HPV oncoproteins E6/E7 may epigenetically upregulate Nectin-4 expression.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal", "source_pmcid": "PMC12361728" }, { "confidence": "medium", "disease": "Oropharyngeal squamous cell carcinoma (OSCC)", "glycan_involvement": "Glycosylation may affect prognostic utility.", "mechanism": "High TROP2 expression has been associated with poor survival in previous studies, but not confirmed in this cohort.", "protein": "TROP2", "protein_enriched": { "function": "May be involved in transcriptional regulation", "gene_name": "ZNF101", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZC7" }, "relationship_type": "prognostic biomarker", "source_pmcid": "PMC12361728" }, { "confidence": "high", "disease": "NAFLD/MASLD", "glycan_involvement": "Phosphatidylcholine is a precursor for glycoprotein and membrane glycan synthesis; supports membrane integrity and VLDL secretion.", "mechanism": "Supplementation reduces hepatic steatosis, oxidative stress, inflammation, and improves liver function and lipid profile.", "protein": "Phosphatidylcholine", "relationship_type": "therapeutic/protective", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "NAFLD/MASLD", "glycan_involvement": "Leptin is a glycoprotein; glycosylation affects its secretion and receptor interaction.", "mechanism": "Elevated leptin correlates with disease severity, oxidative stress, and fibrosis; reduction indicates improvement.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Supports glycoprotein and glycolipid biosynthesis in hepatocytes.", "mechanism": "Supplementation reduces fibrosis scores, possibly by stabilizing membranes and reducing inflammation.", "protein": "Phosphatidylcholine", "relationship_type": "therapeutic/protective", "source_pmcid": "PMC12361734" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates leptin's stability and activity.", "mechanism": "High leptin promotes hepatic stellate cell activation and fibrosis via ROS and cytokine signaling.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12361734" }, { "confidence": "medium", "disease": "Steatohepatitis (MASH/NASH)", "glycan_involvement": "Maintains glycoprotein-rich membrane integrity, reducing cell injury.", "mechanism": "Reduces progression from steatosis to steatohepatitis by lowering oxidative stress and inflammation.", "protein": "Phosphatidylcholine", "relationship_type": "therapeutic/protective", "source_pmcid": "PMC12361734" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Glycosylation affects leptin's bioactivity and half-life.", "mechanism": "Elevated leptin is associated with insulin resistance and T2D risk.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12361734" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2D)", "glycan_involvement": "Supports membrane glycoprotein function in insulin signaling.", "mechanism": "Higher PC levels improve insulin sensitivity and glycemic control.", "protein": "Phosphatidylcholine", "relationship_type": "protective", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "NAFLD/MASLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability.", "mechanism": "Elevated ALT indicates hepatocellular injury; reduction reflects improvement.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "NAFLD/MASLD", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect secretion.", "mechanism": "Elevated AST is a marker of liver injury; reduction indicates therapeutic response.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "NAFLD/MASLD", "glycan_involvement": "Indirect; oxidative stress can alter glycoprotein structure/function.", "mechanism": "Elevated TBARS reflect increased oxidative stress and disease severity; reduction indicates improvement.", "protein": "TBARS", "relationship_type": "biomarker", "source_pmcid": "PMC12361734" }, { "confidence": "high", "disease": "Tumor drug resistance", "glycan_involvement": "Glycosylation affects P-gp stability and function.", "mechanism": "Nanocarriers deliver P-gp siRNA to tumors, reducing P-gp-mediated drug efflux and resistance.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect ferritin's biocompatibility and targeting.", "mechanism": "Ferritin nanocages encapsulate toxic drugs, improving delivery and reducing toxicity.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "medium", "disease": "Bone tissue regeneration", "glycan_involvement": "EGF glycosylation modulates receptor binding and activity.", "mechanism": "EGF gradients in nanofiber scaffolds promote cell migration and tissue regeneration.", "protein": "Epidermal Growth Factor (EGF)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of SHP1 may affect its cellular localization.", "mechanism": "Macrophage membrane-wrapped liposomes deliver SHP1 inhibitor, reducing inflammation.", "protein": "SHP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates receptor binding and clearance.", "mechanism": "Lipoprotein-inspired nanocarriers mimic ApoB-100 to target LDL receptors on tumors.", "protein": "Apolipoprotein B-100 (ApoB-100)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation influences BBB transport efficiency.", "mechanism": "ApoE-mimetic nanocarriers facilitate drug delivery across the BBB via receptor-mediated endocytosis.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Surface glycosylation mediates immune interactions.", "mechanism": "Platelet membrane-coated nanoparticles deliver Toll-like receptor agonists for anti-tumor therapy.", "protein": "Platelet membrane glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycans prevent macrophage phagocytosis.", "mechanism": "RBC membrane-coated nanoparticles evade immune clearance and target atherosclerotic plaques.", "protein": "Red blood cell membrane glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation modulates immune targeting.", "mechanism": "Neutrophil membrane-coated nanoparticles inhibit pro-inflammatory factors.", "protein": "Neutrophil membrane glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "N-terminal glycosylation of targeting peptides increases exosome stability.", "mechanism": "Exosomes deliver miRNA-140 to chondrocytes for OA therapy; glycosylation of targeting peptides enhances stability.", "protein": "Exosomal glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362117" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH is an N-glycosylated glycoprotein; glycosylation affects its stability and bioactivity.", "mechanism": "TSH is elevated in hypothyroidism due to loss of negative feedback from thyroid hormones.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "T4 is derived from thyroglobulin, a glycoprotein; glycosylation of thyroglobulin is essential for hormone synthesis.", "mechanism": "Low T4 is diagnostic for hypothyroidism; T4 replacement is standard therapy.", "protein": "Thyroxine (T4)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12362319" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "T3 is derived from thyroglobulin, a glycoprotein; glycosylation of thyroglobulin is essential for hormone synthesis.", "mechanism": "Low T3 is seen in hypothyroidism; T3 is the active thyroid hormone.", "protein": "Triiodothyronine (T3)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "TSH glycosylation may modulate its bioactivity and clearance, influencing thyroid axis in obesity.", "mechanism": "Obesity is associated with altered TSH levels, possibly due to changes in hypothalamic-pituitary-thyroid axis.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Thyroglobulin glycosylation may affect hormone synthesis in obesity.", "mechanism": "Obesity can alter T4 metabolism and requirements.", "protein": "Thyroxine (T4)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Post-bariatric surgery altered absorption", "glycan_involvement": "Not directly glycosylated, but absorption may be influenced by mucosal glycoproteins.", "mechanism": "Bariatric surgery alters GI anatomy, affecting levothyroxine absorption and dose requirements.", "protein": "Levothyroxine", "relationship_type": "therapeutic target", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Post-bariatric surgery altered absorption", "glycan_involvement": "TSH glycosylation may affect assay results and bioactivity post-surgery.", "mechanism": "TSH is monitored to adjust levothyroxine dosing after surgery.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Post-bariatric surgery altered absorption", "glycan_involvement": "Dependent on thyroglobulin glycosylation for synthesis.", "mechanism": "T3 levels improve after bariatric surgery, reflecting improved thyroid hormone metabolism.", "protein": "Triiodothyronine (T3)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "medium", "disease": "Post-bariatric surgery altered absorption", "glycan_involvement": "Dependent on thyroglobulin glycosylation for synthesis.", "mechanism": "T4 levels are monitored post-surgery to assess adequacy of replacement.", "protein": "Thyroxine (T4)", "relationship_type": "biomarker", "source_pmcid": "PMC12362319" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation affects TSH half-life and receptor interaction.", "mechanism": "TSH is used to titrate levothyroxine therapy in hypothyroid patients.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12362319" }, { "confidence": "high", "disease": "Postoperative sleep disturbance", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "Elevated CRP levels are associated with poor sleep quality after surgery.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12362696" }, { "confidence": "high", "disease": "Depressive symptoms", "glycan_involvement": "Glycosylation modulates CRP's inflammatory signaling.", "mechanism": "Increased CRP correlates with severity of depressive symptoms postoperatively.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12362696" }, { "confidence": "high", "disease": "Postoperative inflammation", "glycan_involvement": "N-glycosylation critical for CRP's function and clearance.", "mechanism": "CRP elevation indicates systemic inflammatory response after surgery.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12362696" }, { "confidence": "medium", "disease": "Postoperative sleep disturbance", "glycan_involvement": "TNF-\u03b1 is glycosylated, which affects receptor binding and bioactivity.", "mechanism": "Elevated TNF-\u03b1 disrupts sleep architecture via neuroinflammatory pathways.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12362696" }, { "confidence": "medium", "disease": "Depressive symptoms", "glycan_involvement": "Glycosylation influences TNF-\u03b1's stability and signaling.", "mechanism": "High TNF-\u03b1 levels contribute to depressive symptoms through neuroimmune modulation.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "causal", "source_pmcid": "PMC12362696" }, { "confidence": "medium", "disease": "Depressive symptoms", "glycan_involvement": "CRP glycosylation may modulate its inflammatory mediator role.", "mechanism": "CRP partially mediates the relationship between sleep disturbance and depression.", "protein": "C-reactive protein", "relationship_type": "mediator", "source_pmcid": "PMC12362696" }, { "confidence": "medium", "disease": "Postoperative inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and activity.", "mechanism": "TNF-\u03b1 elevation reflects acute inflammatory response post-surgery.", "protein": "Tumor necrosis factor-alpha", "relationship_type": "biomarker", "source_pmcid": "PMC12362696" }, { "confidence": "high", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "MSTN is a glycoprotein; glycosylation may affect its secretion/activity.", "mechanism": "Downregulation of MSTN by telmisartan plus exercise increases myofiber size in PAD muscle.", "protein": "Myostatin (MSTN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "\u03b1-SMA is glycosylated; glycosylation may affect cell phenotype.", "mechanism": "\u03b1-SMA-positive cells (myofibroblasts/SMCs) are major sources of TGF-\u03b2 in fibrotic PAD muscle.", "protein": "Alpha-smooth muscle actin (\u03b1-SMA)", "relationship_type": "biomarker", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Endothelial-to-mesenchymal transition (EndMT)", "glycan_involvement": "CD31 is a glycoprotein; glycosylation affects cell adhesion.", "mechanism": "CD31/\u03b1-SMA coexpression marks EndMT, which is ongoing in PAD muscle.", "protein": "CD31/\u03b1-SMA coexpression", "relationship_type": "biomarker", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Muscle fibrosis", "glycan_involvement": "TGF-\u03b21 is glycosylated; glycosylation modulates activity.", "mechanism": "TGF-\u03b21 from \u03b1-SMA-positive cells drives fibrosis in PAD muscle.", "protein": "TGF-\u03b21 (TGFB1)", "relationship_type": "causal", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "MGAT4 catalyzes N-glycan branching on glycoproteins.", "mechanism": "Upregulation of MGAT4 and N-glycan antennae elongation by telmisartan may modulate vascular cell function.", "protein": "MGAT4", "relationship_type": "protective", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "GMPPB is essential for glycoprotein biosynthesis.", "mechanism": "Upregulation of GMPPB by telmisartan may enhance glycosylation capacity in muscle cells.", "protein": "GMPPB", "protein_enriched": { "function": "Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, diff", "gene_name": "DDR1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q08345" }, "relationship_type": "protective", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "Indirect; FBXO32 is not a glycoprotein but regulated by MSTN.", "mechanism": "Downregulation of FBXO32 (Atrogin-1) by telmisartan may reduce muscle atrophy in PAD.", "protein": "Atrogin-1 (FBXO32)", "protein_enriched": { "function": "", "gene_name": "Ube-1c", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9R1R5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "PPAR\u03b3 activation increases N-glycan branching.", "mechanism": "Activation of PPAR\u03b3 by telmisartan enhances fatty acid oxidation and N-glycosylation in muscle.", "protein": "Peroxisome proliferator-activated receptor gamma (PPAR\u03b3)", "protein_enriched": { "function": "Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) a", "gene_name": "PPARG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P37231" }, "relationship_type": "protective", "source_pmcid": "PMC12362707" }, { "confidence": "low", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "KHK is involved in fructose metabolism, supporting glycan biosynthesis.", "mechanism": "Upregulation of KHK by telmisartan may support glycosylation and energy metabolism.", "protein": "KHK", "relationship_type": "protective", "source_pmcid": "PMC12362707" }, { "confidence": "medium", "disease": "Walking impairment", "glycan_involvement": "CD31 glycosylation affects endothelial function.", "mechanism": "Change in proportion of \u03b1-SMA-positive cells classified as ECs (CD31+) correlates with walking speed improvement.", "protein": "CD31 (PECAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12362707" }, { "confidence": "high", "disease": "Glaucoma", "glycan_involvement": "Glycosylation required for proper cell surface expression and receptor binding.", "mechanism": "CD200-CD200R interaction inhibits microglia activation, maintaining retinal homeostasis.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "protective", "source_pmcid": "PMC12363269" }, { "confidence": "high", "disease": "Age-related Macular Degeneration (AMD)", "glycan_involvement": "Glycosylation modulates chemokine-receptor interaction.", "mechanism": "CX3CL1-CX3CR1 axis maintains microglia homeostasis; deficiency leads to microglia accumulation and AMD progression.", "protein": "CX3CL1 (Fractalkine)", "relationship_type": "protective", "source_pmcid": "PMC12363269" }, { "confidence": "medium", "disease": "Uveitis", "glycan_involvement": "Binds \u03b2-galactoside glycans on immune cells, modulating their function.", "mechanism": "Galectins contribute to ocular immune privilege by suppressing inflammation.", "protein": "Galectin", "relationship_type": "protective", "source_pmcid": "PMC12363269" }, { "confidence": "medium", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances immune inhibitory function.", "mechanism": "PD-L1 expression in ocular tissue suppresses T cell activation, reducing inflammation.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "protective", "source_pmcid": "PMC12363269" }, { "confidence": "high", "disease": "Dry Eye Disease (DED)", "glycan_involvement": "Glycosylation affects ligand binding and immune activation.", "mechanism": "Activated DCs expressing CD86 promote onset and progression of DED.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12363269" }, { "confidence": "high", "disease": "Age-related Macular Degeneration (AMD)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "CX3CR1 deficiency leads to microglia migration and subretinal accumulation, contributing to AMD.", "protein": "CX3CR1", "protein_enriched": { "function": "Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune respons", "gene_name": "CX3CR1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P49238" }, "relationship_type": "causal", "source_pmcid": "PMC12363269" }, { "confidence": "medium", "disease": "Anterior Uveitis", "glycan_involvement": "Glycosylation modulates peptide presentation and immune recognition.", "mechanism": "Upregulation on DCs and microglia promotes antigen presentation and inflammation.", "protein": "MHC-II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12363269" }, { "confidence": "medium", "disease": "Anterior Uveitis", "glycan_involvement": "Glycosylation required for surface expression.", "mechanism": "DC maturation marker; increased expression correlates with inflammation.", "protein": "CD83", "relationship_type": "biomarker", "source_pmcid": "PMC12363269" }, { "confidence": "low", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Binds sialylated glycans, modulating immune cell signaling.", "mechanism": "Expressed on plasmacytoid DCs, involved in anti-viral and autoimmune responses in DR.", "protein": "Siglec-H", "relationship_type": "biomarker", "source_pmcid": "PMC12363269" }, { "confidence": "medium", "disease": "Retinitis Pigmentosa (RP)", "glycan_involvement": "Glycosylation required for receptor-ligand interaction.", "mechanism": "CD200R engagement by CD200 inhibits microglia activation, reducing neuroinflammation.", "protein": "CD200R", "relationship_type": "protective", "source_pmcid": "PMC12363269" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects aggregation and clearance.", "mechanism": "Extracellular accumulation of A\u03b2 plaques is a hallmark and driver of AD pathology.", "protein": "Amyloid \u03b2 (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12363324" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is O-glycosylated; glycosylation modulates aggregation propensity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to neurodegeneration.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Lf glycosylation mediates receptor binding and brain targeting.", "mechanism": "Lf-functionalized nanoparticles enhance neuroprotection and drug delivery to neurons.", "protein": "Lactoferrin (Lf)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "PrPC is N-glycosylated; glycosylation affects exosomal sorting and A\u03b2 interaction.", "mechanism": "Exosomal PrPC binds A\u03b2, reducing its accumulation and toxicity.", "protein": "Cellular prion protein (PrPC)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation of RVG29 is essential for neuronal receptor recognition.", "mechanism": "RVG29-modified nanoparticles facilitate targeted delivery to neurons.", "protein": "Rabies virus glycoprotein (RVG29)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "bFGF glycosylation modulates receptor binding and stability.", "mechanism": "bFGF-modified nanocarriers promote neuronal survival and regeneration.", "protein": "Basic fibroblast growth factor (bFGF)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences secretion and neuroprotective function.", "mechanism": "Exosomal cystatin C supports neuronal health and survival.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "NEP glycosylation affects enzymatic activity and exosomal loading.", "mechanism": "Exosomal NEP degrades A\u03b2, reducing plaque formation.", "protein": "Neutral endopeptidase (NEP)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Sensorineural hearing loss", "glycan_involvement": "APP is N- and O-glycosylated; glycosylation influences processing to A\u03b2.", "mechanism": "APP and phosphorylated tau are increased in SNHL, linking hearing loss and dementia.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12363324" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "WGA binds to N-acetylglucosamine residues on glycoproteins of nasal epithelium.", "mechanism": "WGA-modified nanoparticles enhance nose-to-brain delivery via olfactory pathway.", "protein": "Wheat germ agglutinin (WGA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12363324" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation affects stability and activity of Factor VIII.", "mechanism": "Factor VIII deficiency causes impaired coagulation; replacement therapy is used.", "protein": "Factor VIII", "relationship_type": "therapeutic target", "source_pmcid": "PMC12373372" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation required for secretion and clot formation.", "mechanism": "Low fibrinogen levels contribute to bleeding tendency.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "ABO glycosylation modulates plasma Factor VIII levels.", "mechanism": "Low Factor VIII in group O plasma may exacerbate bleeding and anemia.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Skeletal muscle atrophy", "glycan_involvement": "Glycosylation regulates myostatin secretion and activity.", "mechanism": "Elevated serum myostatin correlates with muscle loss under hypoxic stress.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "biomarker", "source_pmcid": "PMC12373372" }, { "confidence": "high", "disease": "Syphilis", "glycan_involvement": "HBsAg is a heavily glycosylated viral envelope protein.", "mechanism": "HBsAg and syphilis seropositivity used for donor screening to prevent transfusion-transmitted infections.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "biomarker", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "N-glycosylation affects albumin stability and half-life.", "mechanism": "Albumin levels reflect plasma protein status in anemia.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation required for secretion and anticoagulant activity.", "mechanism": "Protein C regulates coagulation; deficiency increases thrombosis risk.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation essential for function.", "mechanism": "Antithrombin inhibits thrombin; deficiency leads to hypercoagulability.", "protein": "Antithrombin", "relationship_type": "protective", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "Febrile Non-hemolytic Transfusion Reaction", "glycan_involvement": "Glycosylation patterns modulate immune recognition.", "mechanism": "Leukocyte-derived cytokines and glycoproteins in transfused blood can trigger reactions.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12373372" }, { "confidence": "medium", "disease": "HLA Alloimmunisation", "glycan_involvement": "Glycan epitopes contribute to immunogenicity.", "mechanism": "Alloimmunisation against glycosylated Factor VIII can occur in multitransfused patients.", "protein": "Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC12373372" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "CRP glycosylation affects its stability and function.", "mechanism": "CRP levels rise in response to inflammation and infection, indicating hepatic stress.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Rectal cancer", "glycan_involvement": "Altered glycosylation may modulate CRP's immune functions.", "mechanism": "Elevated CRP is associated with cancer-related inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation impacts albumin's half-life and transport properties.", "mechanism": "Serum albumin decreases in liver dysfunction due to impaired synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Altered N-glycosylation patterns are diagnostic for liver disease.", "mechanism": "Transferrin glycoforms change in liver disease, reflecting hepatic synthetic capacity.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Encephalopathy", "glycan_involvement": "Fc glycan modifications modulate immune response in CNS.", "mechanism": "IgG glycosylation changes may reflect neuroinflammation in encephalopathy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects AGP's immunomodulatory properties.", "mechanism": "AGP increases in acute-phase response, indicating hepatic inflammation.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation is essential for ceruloplasmin stability.", "mechanism": "Ceruloplasmin levels decrease in severe liver disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation modulates haptoglobin's hemoglobin-binding function.", "mechanism": "Haptoglobin is reduced in liver dysfunction due to impaired synthesis.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "low", "disease": "Liver abscess", "glycan_involvement": "Glycosylation affects IgM's complement activation.", "mechanism": "IgM levels may rise in response to infection and abscess formation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "medium", "disease": "Hepatic encephalopathy", "glycan_involvement": "Defective glycosylation reflects hepatic synthetic impairment.", "mechanism": "Altered transferrin glycoforms are associated with hepatic encephalopathy.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378012" }, { "confidence": "high", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Low HDL-c levels (as part of AIP) are associated with increased risk of progression from normoglycemia to prediabetes.", "protein": "High-Density Lipoprotein Cholesterol (HDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "high", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "Lipoproteins contain glycoproteins; glycosylation modulates lipid metabolism.", "mechanism": "Elevated triglycerides (as part of AIP) increase risk of prediabetes via lipotoxicity and insulin resistance.", "protein": "Triglyceride-rich Lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "N-glycosylation of ApoA-I affects HDL function and anti-inflammatory properties.", "mechanism": "ApoA-I in HDL-c exerts antioxidant and anti-inflammatory effects, protecting \u03b2-cells from dysfunction.", "protein": "Apolipoprotein A-I", "relationship_type": "protective", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation of ApoB modulates LDL particle properties.", "mechanism": "ApoB-containing lipoproteins contribute to atherogenic risk, reflected in AIP.", "protein": "Apolipoprotein B", "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "high", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "Non-enzymatic glycation (not classical glycosylation) of hemoglobin.", "mechanism": "Elevated HbA1c is diagnostic for prediabetes and reflects chronic hyperglycemia.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and function.", "mechanism": "Elevated CRP is associated with inflammation and increased cardiovascular risk.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "GGT is glycosylated, affecting its enzymatic activity.", "mechanism": "Elevated GGT is associated with metabolic dysfunction and increased risk of prediabetes.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "ALT is glycosylated, influencing its stability.", "mechanism": "Elevated ALT reflects hepatic dysfunction, which is linked to insulin resistance and prediabetes risk.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "medium", "disease": "Prediabetes (pre-DM)", "glycan_involvement": "AST is glycosylated, affecting its function.", "mechanism": "Elevated AST is associated with metabolic syndrome and prediabetes risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB) with N-glycosylation affecting atherogenicity.", "mechanism": "Elevated LDL-c is a risk factor for atherosclerosis, reflected in AIP.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-c)", "relationship_type": "biomarker", "source_pmcid": "PMC12378059" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation required for secretion and activity; \u03b12\u20136 sialylation enhances cell adhesion.", "mechanism": "Promotes adhesion, invasion, proliferation, fibrosis, and immune suppression in ectopic endometrial cells via Smad and non-Smad pathways.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "high", "disease": "Fibrosis in Endometriosis", "glycan_involvement": "Glycosylation essential for protein stability and ECM interactions.", "mechanism": "Induces fibroblast-to-myofibroblast transdifferentiation and collagen synthesis via Smad2/3 and AKT-dependent NR4A1 phosphorylation.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation affects secretion and stability; not detailed in article.", "mechanism": "Elevated serum and peritoneal fluid levels correlate with disease severity and infertility.", "protein": "GDF-15", "relationship_type": "biomarker", "source_pmcid": "PMC12378113" }, { "confidence": "high", "disease": "Ovarian Endometriosis", "glycan_involvement": "AMH is a dimeric glycoprotein; glycosylation required for function.", "mechanism": "Lower serum AMH levels indicate reduced ovarian reserve in OE patients.", "protein": "AMH (Anti-Mullerian Hormone)", "protein_enriched": { "function": "", "gene_name": "bdhA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q04944" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378113" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Promotes proliferation, differentiation, angiogenesis, and inflammation in endometriotic stromal cells via Smad signaling.", "protein": "Activin A", "protein_enriched": { "function": "Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythr", "gene_name": "INHBA", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G70994MS" ], "uniprot_id": "P08476" }, "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "medium", "disease": "Ovarian Endometriosis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Elevated in cystic fluid; distinguishes OE from other cysts.", "protein": "Inhibin A", "relationship_type": "biomarker", "source_pmcid": "PMC12378113" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "High expression in ectopic endometrium; contributes to estrogen-rich microenvironment and correlates with estrogen receptor alpha.", "protein": "BMP6", "protein_enriched": { "function": "Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation (PubMed:31019025). Also plays an important role in the regul", "gene_name": "BMP6", "glycan_count": 3, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G62765YT", "G57321FI", "G80920RR" ], "uniprot_id": "P22004" }, "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Proteoglycan with glycosaminoglycan chains; glycosylation modulates cell adhesion and invasion.", "mechanism": "Regulates invasive potential of endometriotic cells via TGF-\u03b2 signaling.", "protein": "SDC1 (Syndecan-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378113" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "TGF-\u03b21/2-induced secretion enhances cell adhesion and development of endometriosis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "medium", "disease": "Endometriosis-associated Ovarian Cancer", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Aberrant TGF-\u03b2 signaling parallels malignant processes including invasion and proliferation.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12378113" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "NY-ESO-1 is a glycoprotein; glycosylation may affect antigen processing and presentation.", "mechanism": "NY-ESO-1 is selectively expressed in lung cancer cells and can be targeted by TCR-T cells for immunotherapy.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation may modulate immunogenicity and T cell recognition.", "mechanism": "NY-ESO-1 expression in melanoma enables recognition by NY-ESO-1-specific TCR-T cells, facilitating targeted killing.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "NY-ESO-1 is expressed in ovarian cancer and can be exploited for antigen-specific immunotherapy.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Esophageal cancer", "glycan_involvement": "Glycosylation may affect NY-ESO-1 processing.", "mechanism": "NY-ESO-1 is a biomarker and target for T cell-based therapies in esophageal cancer.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "Glycosylation may impact antigenicity.", "mechanism": "NY-ESO-1 expression in bladder cancer allows for targeted immunotherapy.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "NY-ESO-1 is expressed in prostate cancer and can be targeted by TCR-T cells.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect antigen presentation and immune activation.", "mechanism": "OVV-01 induces NY-ESO-1 expression in H22 hepatocellular carcinoma cells, enhancing T cell-mediated killing.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation may modulate antigen processing.", "mechanism": "OVV-01 enables NY-ESO-1 expression in Caski cervical cancer cells, facilitating TCR-T cell therapy.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "Glycosylation may influence antigen presentation.", "mechanism": "OVV-01 induces NY-ESO-1 in colon cancer cells (e.g., HCT116), promoting T cell activation and tumor killing.", "protein": "NY-ESO-1 (CTAG1B)", "protein_enriched": { "function": "Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play ", "gene_name": "DKK2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "Q9UBU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Solid tumors (general)", "glycan_involvement": "Glycosylation of G protein is essential for viral infectivity and immune recognition.", "mechanism": "VSV G protein mediates viral entry and tumor cell infection, enabling selective oncolysis and immune activation.", "protein": "VSV Glycoprotein (G protein)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC12378170" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation affects NT-proBNP stability and detection.", "mechanism": "Elevated NT-proBNP reflects increased cardiac wall stress and severity of HF.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378172" }, { "confidence": "high", "disease": "Myocardial Injury", "glycan_involvement": "Glycosylation may influence cTnI clearance and immunoreactivity.", "mechanism": "Elevated cTnI indicates myocardial cell damage post-AMI.", "protein": "cTnI (Cardiac Troponin I)", "relationship_type": "biomarker", "source_pmcid": "PMC12378172" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "O-glycosylation modulates peptide stability and bioactivity.", "mechanism": "ARNI increases adrenomedullin activity, promoting vasodilation and natriuresis.", "protein": "Adrenomedullin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378172" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects GLP-1 receptor binding and half-life.", "mechanism": "ARNI increases GLP-1 activity, improving insulin sensitivity and glucose metabolism.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378172" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation influences peptide stability and receptor interaction.", "mechanism": "Enhanced by ARNI, natriuretic peptides reduce cardiac preload and afterload.", "protein": "Natriuretic peptides", "relationship_type": "protective", "source_pmcid": "PMC12378172" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "Glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Inhibition of neprilysin by ARNI increases beneficial peptide hormones.", "protein": "Neprilysin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378172" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation modulates DPP4 enzymatic activity.", "mechanism": "ARNI reduces DPP4 activity, enhancing insulin sensitivity.", "protein": "Dipeptidyl peptidase 4 (DPP4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378172" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Potential glycosylation may affect nuclear localization and activity.", "mechanism": "Upregulated by ARNI, Sirtuin-1 alleviates mitochondrial damage and oxidative stress.", "protein": "Sirtuin-1", "relationship_type": "protective", "source_pmcid": "PMC12378172" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Potential glycosylation may regulate mitochondrial targeting.", "mechanism": "Upregulated by ARNI, Sirtuin-3 improves mitochondrial function.", "protein": "Sirtuin-3", "relationship_type": "protective", "source_pmcid": "PMC12378172" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Potential glycosylation may affect stability and transcriptional activity.", "mechanism": "Downregulation by ARNI reduces hypoxia-induced metabolic dysfunction.", "protein": "Hypoxia-inducible factor 1 alpha (HIF1A)", "relationship_type": "causal", "source_pmcid": "PMC12378172" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "O-glycosylation critical for mucus barrier function.", "mechanism": "Reduced butyrate production leads to decreased Mucin-2 expression, weakening mucus barrier and promoting inflammation.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "Glycosylation modulates tight junction stability.", "mechanism": "Butyrate enhances claudin-2 expression, improving tight junction integrity and reducing gut permeability.", "protein": "Claudin-2", "relationship_type": "protective", "source_pmcid": "PMC12378288" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "Glycosylation affects stability and detection.", "mechanism": "Stool calprotectin levels correlate with inflammation severity and microbial diversity loss.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "N-glycosylation required for membrane localization and function.", "mechanism": "Butyrate-induced HDAC inhibition upregulates P-glycoprotein, enhancing efflux of toxins and xenobiotics.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378288" }, { "confidence": "high", "disease": "Allergy", "glycan_involvement": "O-glycosylation essential for mucosal immunity.", "mechanism": "Gut bacteria stimulate IgA production, promoting immune tolerance and reducing allergy risk.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects hormone stability.", "mechanism": "SCFA signaling via GPCRs increases GLP-1, regulating appetite and energy balance.", "protein": "GLP-1", "relationship_type": "protective", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "Glycosylation modulates activity.", "mechanism": "SCFA-induced GPCR activation increases GLP-2, supporting epithelial repair.", "protein": "GLP-2", "relationship_type": "protective", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Propionate activation of GPR41 increases leptin secretion, influencing food intake.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "Glycosylation affects cytokine activity.", "mechanism": "Cachexia associated with elevated TNFa and altered gut microbiome.", "protein": "Tumor necrosis factor-alpha (TNFa)", "relationship_type": "causal", "source_pmcid": "PMC12378288" }, { "confidence": "medium", "disease": "Celiac Disease", "glycan_involvement": "O-glycosylation essential for barrier function.", "mechanism": "Altered GMB increases Mucin-2 degradation, compromising barrier and promoting autoimmunity.", "protein": "Mucin-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378288" }, { "confidence": "high", "disease": "Stevens-Johnson syndrome (SJS)", "glycan_involvement": "HLA-B*15:02 is a glycoprotein; glycosylation is essential for proper folding and surface expression.", "mechanism": "Presents drug antigen to cytotoxic T cells, triggering immune-mediated keratinocyte death.", "protein": "HLA-B*15:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G04854VP", "G08918WF", "G10488MI", "G15664MX", "G20706XG", "G27058EU", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G62765YT", "G70101JE", "G72747WU", "G77669RF", "G80920RR", "G90659AW", "G92135MA", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "high", "disease": "Toxic epidermal necrolysis (TEN)", "glycan_involvement": "N-glycosylation required for HLA surface expression.", "mechanism": "Same as above; triggers cytotoxic T cell response upon drug exposure.", "protein": "HLA-B*15:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G04854VP", "G08918WF", "G10488MI", "G15664MX", "G20706XG", "G27058EU", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G62765YT", "G70101JE", "G72747WU", "G77669RF", "G80920RR", "G90659AW", "G92135MA", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "high", "disease": "DRESS", "glycan_involvement": "N-glycosylation required for HLA function.", "mechanism": "Presents drug-modified peptides to T cells, leading to systemic hypersensitivity.", "protein": "HLA-A*31:01", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "medium", "disease": "Stevens-Johnson syndrome (SJS)", "glycan_involvement": "N-glycosylation required for HLA function.", "mechanism": "Associated with increased risk of SJS/TEN via T cell activation.", "protein": "HLA-A*31:01", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "medium", "disease": "Lamotrigine-induced SCARs", "glycan_involvement": "N-glycosylation required for HLA function.", "mechanism": "Associated with increased risk of SCARs via antigen presentation.", "protein": "HLA-A*24:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "medium", "disease": "Phenytoin-induced SCARs", "glycan_involvement": "N-glycosylation required for HLA function.", "mechanism": "Associated with increased risk of SCARs via antigen presentation.", "protein": "HLA-B*13:01", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "medium", "disease": "SCARs induced by carbamazepine, lamotrigine, and phenytoin", "glycan_involvement": "N-glycosylation required for HLA-DRB1 function.", "mechanism": "MHC class II presentation to CD4+ T cells, contributing to hypersensitivity.", "protein": "HLA-DRB1*03:01", "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "high", "disease": "Phenytoin-induced SCARs", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Poor metabolizer genotype leads to increased phenytoin levels and risk of hypersensitivity.", "protein": "CYP2C9*3", "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "high", "disease": "SCARs induced by carbamazepine, phenytoin, and phenobarbital", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Poor metabolizer genotype increases drug levels, predisposing to hypersensitivity.", "protein": "CYP2C19*2", "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "medium", "disease": "Lamotrigine-induced SCARs", "glycan_involvement": "N-glycosylation required for HLA function.", "mechanism": "Associated with increased risk of SCARs via antigen presentation.", "protein": "HLA-B*15:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G04854VP", "G08918WF", "G10488MI", "G15664MX", "G20706XG", "G27058EU", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G62765YT", "G70101JE", "G72747WU", "G77669RF", "G80920RR", "G90659AW", "G92135MA", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378293" }, { "confidence": "high", "disease": "Small cell lung cancer (SCLC)", "glycan_involvement": "N-glycosylation confirmed by increased molecular weight; may affect protein stability and immune recognition.", "mechanism": "B7-H6 is overexpressed in SCLC and mediates immune evasion; targeting B7-H6 with bispecific antibodies redirects T/NK cells for tumor cell killing.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378318" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "N-glycosylation detected; may influence cell surface localization and antibody binding.", "mechanism": "B7-H6 is selectively expressed in NSCLC tumor cells, serving as a diagnostic marker and therapeutic target.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation observed; may modulate immune interactions.", "mechanism": "B7-H6 is overexpressed in hepatic tumors; bispecific antibodies enable immune cell-mediated cytotoxicity.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378318" }, { "confidence": "high", "disease": "Pancreatic adenocarcinoma", "glycan_involvement": "N-glycosylation present; may affect antibody recognition.", "mechanism": "Tumor-restricted expression of B7-H6 in pancreatic cancer supports its use as a biomarker and target for immunotherapy.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Breast carcinoma", "glycan_involvement": "N-glycosylation detected; may influence expression and immune targeting.", "mechanism": "B7-H6 shows heterogeneous expression in breast cancer (e.g., MCF-7+ vs. MDA-MB-231\u2212), indicating context-dependent biomarker utility.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation likely; functional impact not detailed.", "mechanism": "B7-H6 is selectively expressed in gastric tumors, supporting its role as a diagnostic and therapeutic target.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation likely; may affect immune recognition.", "mechanism": "B7-H6 is overexpressed in colorectal cancer, enabling tumor-specific immune targeting.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "N-glycosylation likely; functional impact not specified.", "mechanism": "B7-H6 is a marker for oral squamous cell carcinoma, facilitating targeted immunotherapy.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "N-glycosylation likely; functional impact not specified.", "mechanism": "B7-H6 is expressed in cervical cancer, supporting its use in diagnosis and therapy.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378318" }, { "confidence": "high", "disease": "Chemoresistant solid tumors", "glycan_involvement": "N-glycosylation confirmed; may influence antibody binding and immune activation.", "mechanism": "B7-H6-targeted bispecific antibodies and IL-15 fusion proteins eradicate chemo-resistant tumors by enhancing NK/T cell cytotoxicity.", "protein": "B7-H6", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q6ZMI9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378318" }, { "confidence": "medium", "disease": "Exocrine pancreatic carcinoma", "glycan_involvement": "Glycosylation modulates E-cadherin stability and cell\u2013cell adhesion.", "mechanism": "E-cadherin expression assessed as a marker of cell adhesion and tumor progression.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378328" }, { "confidence": "medium", "disease": "Exocrine pancreatic carcinoma", "glycan_involvement": "Glycosylation affects c-KIT receptor function and signaling.", "mechanism": "c-KIT expression evaluated for prognostic significance in pancreatic carcinoma.", "protein": "c-KIT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378328" }, { "confidence": "medium", "disease": "Congestive heart failure (CHF)", "glycan_involvement": "Glycosylation regulates mast cell granule content and mediator release.", "mechanism": "Mast cell degranulation releases prothrombotic and vasoactive factors, contributing to myocardial inflammation and CHF.", "protein": "Mast cell tryptase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378328" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "N-glycosylation of spike protein is essential for infectivity and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry and pathogenesis in FIP.", "protein": "Feline coronavirus spike protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378328" }, { "confidence": "high", "disease": "Feline leukaemia virus infection", "glycan_involvement": "Glycosylation impacts receptor binding and immune escape.", "mechanism": "Envelope glycoprotein mediates viral entry and immune modulation.", "protein": "Feline leukaemia virus envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378328" }, { "confidence": "high", "disease": "Feline immunodeficiency virus infection", "glycan_involvement": "N-glycosylation shields epitopes from immune recognition.", "mechanism": "Envelope glycoprotein facilitates viral entry and persistence.", "protein": "Feline immunodeficiency virus envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12378328" }, { "confidence": "medium", "disease": "Congestive heart failure (CHF)", "glycan_involvement": "Glycosylation may affect troponin stability and detection.", "mechanism": "Elevated troponin I indicates myocardial injury in CHF.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378328" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "No direct glycan involvement; targets viral RNA polymerase.", "mechanism": "GS-441524 inhibits viral replication, improving FIP survival.", "protein": "GS-441524", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378328" }, { "confidence": "medium", "disease": "Cannabis intoxication", "glycan_involvement": "Glycosylation of CB1/CB2 receptors modulates ligand binding.", "mechanism": "THC interacts with glycoprotein cannabinoid receptors, causing neurologic and behavioral signs.", "protein": "Delta-9-tetrahydrocannabinol (THC)", "relationship_type": "causal", "source_pmcid": "PMC12378328" }, { "confidence": "medium", "disease": "Anesthesia-related stress", "glycan_involvement": "CBD modulates glycoprotein receptors involved in autonomic regulation.", "mechanism": "CBD enhances parasympathetic tone, improving comfort under anesthesia.", "protein": "Cannabidiol (CBD)", "relationship_type": "protective", "source_pmcid": "PMC12378328" }, { "confidence": "high", "disease": "Cutaneous NK-cell lymphoma", "glycan_involvement": "CLA is a glycosylated homing receptor; glycosylation is essential for E-selectin binding.", "mechanism": "High CLA expression on NK cells correlates with skin infiltration and worse prognosis.", "protein": "CLA", "relationship_type": "biomarker", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Cutaneous Squamous Cell Carcinoma (cSCC)", "glycan_involvement": "CD16a is N-glycosylated; glycosylation affects receptor stability and function.", "mechanism": "CD16a shedding by ADAM-17 reduces NK cell cytotoxicity in skin tumors.", "protein": "CD16a (Fc\u03b3RIIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378370" }, { "confidence": "medium", "disease": "Hidradenitis Suppurativa", "glycan_involvement": "CD38 is a glycoprotein; glycosylation may modulate its inflammatory signaling.", "mechanism": "CD38 dysregulation on NK cells is associated with inflammation in HS.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "N-glycosylation of ICAM-1 is required for ligand binding and cell trafficking.", "mechanism": "ICAM-1 mediates lymphocyte adhesion and recruitment to inflamed skin.", "protein": "ICAM-1 (CD54)", "relationship_type": "causal", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "CCR10 is glycosylated; glycosylation affects receptor-ligand interactions.", "mechanism": "CCR10-CCL27 axis recruits ILCs and NK cells to inflamed skin; knockout increases damage.", "protein": "CCR10", "relationship_type": "causal", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "E-selectin binds glycosylated CLA; glycosylation is essential for adhesion.", "mechanism": "Reduced E-selectin expression impairs NK cell and T cell infiltration in melanoma.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "CD56 is heavily glycosylated; glycosylation modulates cell-cell interactions.", "mechanism": "CD56+CD16- NK cells infiltrate psoriatic dermis; high IFN\u03b3 secretion.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12378370" }, { "confidence": "medium", "disease": "Allergic Contact Dermatitis", "glycan_involvement": "CCR8 glycosylation may affect ligand binding and migration.", "mechanism": "CCR8 expression on NK cells is critical for skin homing in ACD.", "protein": "CCR8", "protein_enriched": { "function": "Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection", "gene_name": "CCR8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P51685" }, "relationship_type": "causal", "source_pmcid": "PMC12378370" }, { "confidence": "medium", "disease": "Lichen Planus", "glycan_involvement": "CD69 is glycosylated; glycosylation may regulate surface expression.", "mechanism": "CD69+ NK cells are enriched in early LP lesions, indicating tissue residency.", "protein": "CD69", "protein_enriched": { "function": "Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells ", "gene_name": "CD69", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Herpesvirus infections (HSV, VZV, CMV, EBV, HPV)", "glycan_involvement": "N-glycosylation of CD16a modulates antibody binding and cytotoxicity.", "mechanism": "CD16a-mediated ADCC is crucial for NK cell antiviral defense; deficiency increases susceptibility.", "protein": "CD16a (Fc\u03b3RIIIa)", "relationship_type": "protective", "source_pmcid": "PMC12378370" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "NGAL levels rise rapidly in serum/urine after kidney injury, reflecting tubular damage.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "KIM-1 is heavily glycosylated; glycosylation is required for its cell surface expression.", "mechanism": "KIM-1 is upregulated in injured proximal tubules and released into urine.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Cystatin C is N-glycosylated, influencing its serum half-life.", "mechanism": "Serum cystatin C increases with reduced glomerular filtration rate.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "IL-18 is glycosylated, affecting secretion and activity.", "mechanism": "Urinary IL-18 reflects inflammatory response in renal injury.", "protein": "IL-18", "protein_enriched": { "function": "Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and I", "gene_name": "IL18", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "L-FABP is glycosylated, which may affect renal excretion.", "mechanism": "Urinary L-FABP increases after ischemic or toxic renal injury.", "protein": "L-FABP", "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "CHI3L1 is a glycoprotein; glycosylation modulates its function.", "mechanism": "Urinary CHI3L1 rises in AKI, reflecting tubular stress.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "VCAM-1 is N-glycosylated, affecting cell adhesion properties.", "mechanism": "Elevated VCAM-1 indicates endothelial activation in AKI.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "CXCL10 is glycosylated, influencing chemokine activity.", "mechanism": "CXCL10 increases in AKI, reflecting immune cell recruitment.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation affects stability and renal clearance.", "mechanism": "Serum/urine beta-2-microglobulin rises with tubular dysfunction.", "protein": "Beta-2-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Both are glycoproteins; glycosylation modulates secretion and activity.", "mechanism": "Urinary TIMP-2*IGFBP7 predicts risk of AKI by indicating cell cycle arrest.", "protein": "TIMP-2*IGFBP7 complex", "relationship_type": "biomarker", "source_pmcid": "PMC12378388" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "Gingipains are glycoproteins; their activity may be modulated by glycosylation.", "mechanism": "Gingipains disrupt bone homeostasis by inhibiting osteogenesis and promoting osteoclastogenesis.", "protein": "Gingipains (Kgp, RgpA/B)", "relationship_type": "causal", "source_pmcid": "PMC12378552" }, { "confidence": "high", "disease": "Alveolar bone loss", "glycan_involvement": "Glycosylation may affect gingipain secretion and activity.", "mechanism": "Gingipains exacerbate bone resorption by increasing osteoclast differentiation via exosomal signaling.", "protein": "Gingipains (Kgp, RgpA/B)", "relationship_type": "causal", "source_pmcid": "PMC12378552" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "TRAF6 is a glycoprotein; glycosylation may affect its signaling.", "mechanism": "TRAF6 is upregulated in osteoclasts when miR-146a-5p is downregulated, promoting osteoclastogenesis.", "protein": "TRAF6", "relationship_type": "causal", "source_pmcid": "PMC12378552" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "RANKL is glycosylated; glycosylation affects receptor binding.", "mechanism": "Elevated RANKL in gingival crevicular fluid correlates with disease severity and osteoclast activation.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378552" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "C5a is a glycoprotein fragment; glycosylation affects stability.", "mechanism": "Increased C5a levels indicate complement activation and inflammation.", "protein": "C5a", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11453" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378552" }, { "confidence": "high", "disease": "Periodontitis", "glycan_involvement": "OPG glycosylation affects its stability and function.", "mechanism": "OPG inhibits RANKL-mediated osteoclastogenesis; degraded by gingipains, reducing protection.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "protective", "source_pmcid": "PMC12378552" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "Integrin \u03b21 glycosylation is essential for cell adhesion.", "mechanism": "Gingipains degrade integrin \u03b21, inhibiting BMSC proliferation and osteogenic differentiation.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "causal", "source_pmcid": "PMC12378552" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "CD9 is glycosylated; glycosylation affects exosome formation.", "mechanism": "CD9 is an exosomal marker; increased in BMSC-derived exosomes during disease.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378552" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "CD81 is glycosylated; glycosylation affects exosome formation.", "mechanism": "CD81 is an exosomal marker; increased in BMSC-derived exosomes during disease.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378552" }, { "confidence": "medium", "disease": "Periodontitis", "glycan_involvement": "BMP-2 glycosylation affects secretion and activity.", "mechanism": "Gingipains suppress BMP-2 expression, inhibiting osteogenic differentiation.", "protein": "BMP-2", "relationship_type": "causal", "source_pmcid": "PMC12378552" }, { "confidence": "high", "disease": "Tongue Squamous Cell Carcinoma (TSCC)", "glycan_involvement": "PD-L1 is a transmembrane glycoprotein; glycosylation affects its stability and immune interactions.", "mechanism": "PD-L1 overexpression on tumor cells inhibits T-cell activation, promoting immune evasion and tumor progression.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "Tongue Squamous Cell Carcinoma (TSCC)", "glycan_involvement": "Glycosylation may influence antibody binding and PD-L1 function.", "mechanism": "PD-L1 blockade with antibodies can restore T-cell activity and is approved for immunotherapy in TSCC.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation modulates PD-L1 cell surface expression and immune recognition.", "mechanism": "High PD-L1 expression correlates with advanced stage and shorter disease-free survival.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Glycosylation status may affect PD-L1 stability and function.", "mechanism": "PD-L1 expression regulated by ERK/MAPK pathway, contributing to immune escape.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "Tongue Squamous Cell Carcinoma (TSCC)", "glycan_involvement": "IDO is not a glycoprotein; no direct glycan involvement.", "mechanism": "IDO expression creates an immunosuppressive microenvironment by depleting tryptophan and producing kynurenine, inhibiting T-cell responses.", "protein": "IDO", "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "Tongue Squamous Cell Carcinoma (TSCC)", "glycan_involvement": "Not applicable.", "mechanism": "IDO inhibitors may restore anti-tumor immunity and are under investigation for immunotherapy.", "protein": "IDO", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma", "glycan_involvement": "Not applicable.", "mechanism": "High IDO expression is associated with poor prognosis and immune evasion.", "protein": "IDO", "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Not applicable.", "mechanism": "IDO overexpression contributes to immunosuppression and poor prognosis.", "protein": "IDO", "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Not applicable.", "mechanism": "IDO expression promotes immune evasion and correlates with poor outcomes.", "protein": "IDO", "relationship_type": "biomarker", "source_pmcid": "PMC12378751" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect PD-L1 immunogenicity and therapeutic efficacy.", "mechanism": "PD-L1 blockade is effective in restoring immune response in melanoma.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378751" }, { "confidence": "high", "disease": "MACE", "glycan_involvement": "IgG autoantibody glycosylation may affect effector function and receptor binding.", "mechanism": "Seropositivity for AT1R-AAs is associated with increased risk of major adverse cardiovascular events after STEMI via sustained AT1R activation.", "protein": "AT1R-AAs", "relationship_type": "biomarker", "source_pmcid": "PMC12378766" }, { "confidence": "high", "disease": "MACE", "glycan_involvement": "IgG autoantibody glycosylation may affect effector function and receptor binding.", "mechanism": "Seropositivity for ETAR-AAs is associated with increased risk of major adverse cardiovascular events after STEMI via sustained ETAR activation.", "protein": "ETAR-AAs", "relationship_type": "biomarker", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "No-reflow phenomenon", "glycan_involvement": "IgG glycosylation may modulate inflammatory activity.", "mechanism": "AT1R-AAs contribute to microvascular dysfunction and no-reflow by promoting vasoconstriction and inflammation.", "protein": "AT1R-AAs", "relationship_type": "causal", "source_pmcid": "PMC12378766" }, { "confidence": "high", "disease": "No-reflow phenomenon", "glycan_involvement": "IgG glycosylation may modulate inflammatory activity.", "mechanism": "ETAR-AAs are linked to no-reflow after STEMI by inducing sustained ETAR signaling and microvascular inflammation.", "protein": "ETAR-AAs", "relationship_type": "causal", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "Adverse left ventricular remodeling", "glycan_involvement": "IgG glycosylation may influence fibrotic signaling.", "mechanism": "AT1R-AAs promote myocardial fibrosis and adverse remodeling via chronic receptor activation.", "protein": "AT1R-AAs", "relationship_type": "causal", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "Adverse left ventricular remodeling", "glycan_involvement": "IgG glycosylation may influence fibrotic signaling.", "mechanism": "ETAR-AAs promote myocardial fibrosis and adverse remodeling via chronic receptor activation.", "protein": "ETAR-AAs", "relationship_type": "causal", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation of AT1R may affect receptor expression and ligand binding.", "mechanism": "AT1R is a target for angiotensin receptor blockers (ARBs) to counteract autoantibody-mediated receptor activation.", "protein": "AT1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "STEMI", "glycan_involvement": "Glycosylation of ETAR may affect receptor expression and ligand binding.", "mechanism": "ETAR is a target for endothelin receptor antagonists to counteract autoantibody-mediated receptor activation.", "protein": "ETAR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378766" }, { "confidence": "high", "disease": "MACE", "glycan_involvement": "Combined IgG glycosylation profiles may amplify pathogenic effects.", "mechanism": "Double seropositivity for AT1R-AAs and ETAR-AAs confers highest risk for MACE after STEMI due to synergistic receptor activation.", "protein": "AT1R-AAs + ETAR-AAs (double seropositivity)", "relationship_type": "biomarker", "source_pmcid": "PMC12378766" }, { "confidence": "medium", "disease": "Coronary microvascular obstruction", "glycan_involvement": "IgG glycosylation may modulate immune-mediated vascular injury.", "mechanism": "Autoantibody-mediated activation of AT1R and ETAR leads to microvascular inflammation and obstruction.", "protein": "AT1R-AAs + ETAR-AAs", "relationship_type": "causal", "source_pmcid": "PMC12378766" }, { "confidence": "high", "disease": "Pleomorphic Giant Cell Adenocarcinoma (PGCA) of the Prostate", "glycan_involvement": "Increased N-glycosylation branching on cell surface proteins, facilitating tumor progression and resistance.", "mechanism": "MGAT5 mutation promotes aberrant N-glycan branching, enhancing invasion, metastasis, and immune evasion.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12378786" }, { "confidence": "medium", "disease": "Therapeutic Resistance in Prostate Cancer", "glycan_involvement": "Branched N-glycans on immune checkpoint proteins.", "mechanism": "MGAT5 upregulation leads to branched N-glycans that enhance PD-1/PD-L1 interactions, promoting immune escape and resistance to immunotherapy.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "causal", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Pleomorphic Giant Cell Adenocarcinoma (PGCA) of the Prostate", "glycan_involvement": "Loss of glycosylated E-cadherin disrupts cell\u2013cell adhesion.", "mechanism": "CDH1 mutation/loss drives epithelial\u2013mesenchymal transition (EMT), increasing invasiveness and metastasis.", "protein": "CDH1 (E-cadherin)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12378786" }, { "confidence": "medium", "disease": "Pleomorphic Giant Cell Adenocarcinoma (PGCA) of the Prostate", "glycan_involvement": "As a secreted glycoprotein, altered glycosylation may affect enzyme activity and substrate interactions.", "mechanism": "ADAMTS7 mutation promotes extracellular matrix remodeling, facilitating metastasis.", "protein": "ADAMTS7", "protein_enriched": { "function": "Metalloprotease (PubMed:16585064, PubMed:39672391). Was previously shown to degrade COMP (PubMed:16585064). However, a later study found no activity against COMP (PubMed:39672391)", "gene_name": "ADAMTS7", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G53434XO", "G83460ZZ" ], "uniprot_id": "Q9UKP4" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Prostate Adenocarcinoma", "glycan_involvement": "KLK3 is a secreted glycoprotein; glycosylation affects its stability and detection.", "mechanism": "KLK3 is a diagnostic marker for prostate cancer; loss of expression in PGCA indicates dedifferentiation.", "protein": "KLK3 (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Metastatic Prostate Cancer", "glycan_involvement": "N-glycan branching enhances cell motility and metastatic potential.", "mechanism": "MGAT5 mutation correlates with increased metastasis and poor survival.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Metastatic Prostate Cancer", "glycan_involvement": "Glycosylation of E-cadherin is essential for its adhesive function.", "mechanism": "CDH1 loss is associated with high Gleason score and metastasis.", "protein": "CDH1 (E-cadherin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12378786" }, { "confidence": "medium", "disease": "Pleomorphic Giant Cell Adenocarcinoma (PGCA) of the Prostate", "glycan_involvement": "Potential glycosylation may affect receptor signaling and immune modulation.", "mechanism": "DRD5 mutation may contribute to immune evasion and cell survival.", "protein": "DRD5", "protein_enriched": { "function": "Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase", "gene_name": "DRD5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P21918" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12378786" }, { "confidence": "medium", "disease": "Prostate Adenocarcinoma", "glycan_involvement": "Potential glycosylation may affect enzyme stability.", "mechanism": "AMACR is a diagnostic marker; loss in PGCA indicates dedifferentiation.", "protein": "AMACR", "relationship_type": "biomarker", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Biochemical Recurrence in Prostate Cancer", "glycan_involvement": "Aberrant N-glycosylation patterns serve as recurrence biomarkers.", "mechanism": "MGAT5 mutation is predictive of recurrence and poor prognosis.", "protein": "MGAT5", "protein_enriched": { "function": "Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosacc", "gene_name": "FUT5", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q11128" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378786" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "LDL particles contain apolipoprotein B, a glycoprotein; glycosylation affects LDL receptor binding and clearance.", "mechanism": "Elevated LDL promotes atherosclerotic plaque formation.", "protein": "LDL cholesterol", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "high", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "HDL contains apolipoprotein A-I, a glycoprotein; glycosylation modulates anti-inflammatory properties.", "mechanism": "HDL facilitates reverse cholesterol transport, reducing plaque burden.", "protein": "HDL cholesterol", "relationship_type": "protective", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Apolipoproteins in these particles are glycosylated, influencing metabolism and vascular effects.", "mechanism": "Elevated triglycerides contribute to endothelial dysfunction and plaque formation.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates fibrinogen's clotting activity and clearance.", "mechanism": "High fibrinogen increases blood viscosity and clot formation.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects PAI-1 stability and activity.", "mechanism": "Elevated PAI-1 inhibits fibrinolysis, promoting thrombosis.", "protein": "PAI-1", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune detection and modulates vascular effects.", "mechanism": "Gp120 triggers monocyte activation and endothelial apoptosis, contributing to atherosclerosis.", "protein": "HIV gp120", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Tat glycosylation affects its secretion and cellular uptake.", "mechanism": "Tat protein induces endothelial dysfunction and inflammation.", "protein": "HIV Tat", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "high", "disease": "AIDS-defining illness", "glycan_involvement": "N-glycosylation of CD4 modulates HIV binding and immune signaling.", "mechanism": "Low CD4 count indicates immune suppression and increased risk of AIDS-defining illness.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12378808" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates platelet receptor function and drug response.", "mechanism": "Antiplatelet drugs inhibit platelet glycoprotein-mediated aggregation, reducing CAD risk.", "protein": "Platelet glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12378808" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation is essential for secretion and activity of coagulation factors.", "mechanism": "Elevated coagulation factors increase thrombotic risk in obesity and HIV.", "protein": "Coagulation factors", "relationship_type": "causal", "source_pmcid": "PMC12378808" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "PAI-1 is glycosylated, which affects its stability and activity.", "mechanism": "High PAI-1 inhibits fibrinolysis, increasing risk of thrombosis.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12379029" }, { "confidence": "high", "disease": "Pulmonary embolism (PE)", "glycan_involvement": "Glycosylation modulates PAI-1 plasma half-life.", "mechanism": "Elevated PAI-1 impairs thrombus dissolution, promoting PE.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12379029" }, { "confidence": "high", "disease": "Paradoxical embolism (PDE)", "glycan_involvement": "Glycosylation may influence PAI-1 secretion and function.", "mechanism": "PAI-1 4G/4G genotype increases PAI-1 levels, facilitating arterial embolism via right-to-left shunt.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12379029" }, { "confidence": "high", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation affects PAI-1 activity in plasma.", "mechanism": "PAI-1 gene variant (4G/4G) confers genetic thrombophilia.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12379029" }, { "confidence": "medium", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Fibrinogen glycosylation is essential for its function in clot formation.", "mechanism": "Low fibrinogen and high D-dimer indicate ongoing thrombosis and fibrinolysis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12379029" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation is critical for \u03b22-glycoprotein I immunogenicity.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are tested to rule out antiphospholipid syndrome.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12379029" }, { "confidence": "medium", "disease": "Acute cerebral infarction", "glycan_involvement": "Glycosylation affects PAI-1's inhibitory function.", "mechanism": "Elevated PAI-1 impairs fibrinolysis, increasing risk of cerebral infarction.", "protein": "Plasminogen activator inhibitor-1 (PAI-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12379029" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CEA glycosylation affects its stability and detection as a biomarker", "mechanism": "Serum CEA levels reduced by thymol, indicating decreased tumor burden", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CA 19-9 is a sialylated glycan epitope on mucins, relevant for cancer detection", "mechanism": "Thymol lowers CA 19-9, reflecting reduced cancer activity", "protein": "Cancer Antigen 19-9 (CA 19-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12379064" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Not directly glycosylated, but apoptosis may affect glycoprotein turnover", "mechanism": "Thymol reduces caspase-3 activity, indicating decreased apoptosis in tumor tissue", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Glycosylation modulates claudin-1 localization and barrier function", "mechanism": "Thymol upregulates claudin-1, improving tight junction integrity", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Gut barrier dysfunction", "glycan_involvement": "Glycosylation affects occludin stability and function", "mechanism": "Thymol increases occludin expression, enhancing epithelial barrier", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "medium", "disease": "Gut barrier dysfunction", "glycan_involvement": "N-glycosylation required for PepT1 trafficking and activity", "mechanism": "Thymol modulates PepT1 gene expression, improving nutrient absorption", "protein": "Peptide transporter 1 (PepT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation influences TNF-alpha secretion and receptor binding", "mechanism": "Thymol downregulates TNF-alpha, reducing inflammatory response", "protein": "TNF-alpha", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects IL-1beta stability and activity", "mechanism": "Thymol suppresses IL-1beta expression, mitigating inflammation", "protein": "IL-1beta", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates IL-6 secretion and receptor interaction", "mechanism": "Thymol reduces IL-6 levels, lowering inflammatory signaling", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379064" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation maintains claudin-1 function in oral mucosa", "mechanism": "Thymol-containing oral care products enhance claudin-1, supporting oral epithelial barrier", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC12379064" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of \u03b22 glycoprotein I affects antigenicity and antibody binding.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are diagnostic markers for APS and mediate thrombosis.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Bilateral adrenal hemorrhage", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies promote thrombosis in adrenal veins, leading to hemorrhage.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "IgG glycosylation may influence antibody effector function.", "mechanism": "Elevated anticardiolipin IgG is a diagnostic criterion for APS.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12379092" }, { "confidence": "medium", "disease": "Primary adrenal insufficiency", "glycan_involvement": "Glycosylation may affect pathogenicity of autoantibodies.", "mechanism": "Anticardiolipin IgG positivity is correlated with risk of adrenal insufficiency via thrombosis.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "causal", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Autoantibody glycosylation may modulate immune response.", "mechanism": "Presence of lupus anticoagulant is a diagnostic marker for APS.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Venous thrombosis", "glycan_involvement": "Glycosylation influences \u03b22 glycoprotein I structure and immune interactions.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies induce venous thrombosis via endothelial activation.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12379092" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antigenicity and immune complex formation.", "mechanism": "Anti-\u03b22 glycoprotein I antibodies are frequently present in SLE and indicate overlap with APS.", "protein": "\u03b22 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12379092" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "IgM glycosylation may influence antibody stability and function.", "mechanism": "Elevated anticardiolipin IgM is a diagnostic marker for APS.", "protein": "anticardiolipin antibody (IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC12379092" }, { "confidence": "medium", "disease": "Bilateral adrenal hemorrhage", "glycan_involvement": "Glycan modifications could be exploited for therapeutic antibody design.", "mechanism": "Targeting anti-\u03b22 glycoprotein I antibodies may reduce risk of adrenal hemorrhage.", "protein": "\u03b22 glycoprotein I", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Primary adrenal insufficiency", "glycan_involvement": "Glycosylation modulates immune response and pathogenicity.", "mechanism": "Thrombosis mediated by anti-\u03b22 glycoprotein I antibodies leads to adrenal infarction and insufficiency.", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12379092" }, { "confidence": "high", "disease": "Lower Respiratory Tract Infection (LRTI)", "glycan_involvement": "Glycosylation of OMPs facilitates adhesion to host cell receptors.", "mechanism": "OMPs mediate bacterial attachment and colonization of host respiratory epithelium.", "protein": "Outer Membrane Proteins (OMPs)", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "high", "disease": "Hospital-acquired Pneumonia", "glycan_involvement": "Glycosylated biofilm components enhance structural integrity and resistance.", "mechanism": "Biofilm glycoproteins protect bacteria from immune clearance and antibiotics, promoting persistent infection.", "protein": "Biofilm Matrix Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "medium", "disease": "Lower Respiratory Tract Infection (LRTI)", "glycan_involvement": "Glycosylation aids OMV stability and host interaction.", "mechanism": "OMV glycoproteins deliver virulence factors and modulate host immune response.", "protein": "Outer Membrane Vesicle (OMV) Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "medium", "disease": "Chronic Respiratory Disorders", "glycan_involvement": "Glycosylated biofilm matrix resists phagocytosis and dehydration.", "mechanism": "Biofilm formation exacerbates chronic infection and inflammation.", "protein": "Biofilm Matrix Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "medium", "disease": "Hospital-acquired Pneumonia", "glycan_involvement": "Glycosylation enhances OMP-mediated device adherence.", "mechanism": "OMPs facilitate colonization of medical devices (e.g., ventilators), leading to pneumonia.", "protein": "Outer Membrane Proteins (OMPs)", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "medium", "disease": "Hospital-acquired Pneumonia", "glycan_involvement": "Glycosylation modulates OMV-host interactions.", "mechanism": "OMVs contribute to immune evasion and dissemination in hospital settings.", "protein": "Outer Membrane Vesicle (OMV) Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "high", "disease": "Lower Respiratory Tract Infection (LRTI)", "glycan_involvement": "Glycosylation of matrix proteins is critical for biofilm resilience.", "mechanism": "Biofilm formation increases resistance to antibiotics, leading to persistent LRTI.", "protein": "Biofilm Matrix Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12379561" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "OPG inhibits RANKL, preventing osteoclast formation and bone resorption.", "protein": "Osteoprotegerin (OPG)", "protein_enriched": { "function": "Acts as a decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostas", "gene_name": "TNFRSF11B", "glycan_count": 30, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G06356OH", "G22140GZ", "G31852PQ", "G33609NS", "G37868ZX", "G41247ZX", "G50045TK", "G62765YT", "G80920RR", "G15664MX", "G08146BT", "G22310AV", "G23863VK", "G29880MM", "G42962KI", "G44215PV", "G45495MK", "G46687AB", "G57818FI", "G61937QU", "G66163OV", "G71146HJ", "G75983OB", "G81263BG", "G84452RH", "G86795LJ", "G90093AU", "G96577RX", "G49108TO" ], "uniprot_id": "O00300" }, "relationship_type": "protective", "source_pmcid": "PMC12379731" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation affects receptor binding and function.", "mechanism": "RANKL promotes osteoclast differentiation and bone resorption.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal", "source_pmcid": "PMC12379731" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation critical for receptor function and ligand binding.", "mechanism": "IL-6R/gp130 mediates IL-6 signaling, promoting osteoclastogenesis and inflammation; blockade reduces bone loss.", "protein": "IL-6R/gp130", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379731" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation required for receptor surface expression.", "mechanism": "IL-11R\u03b1/gp130 signaling induces osteoclastogenesis and suppresses osteoblast activity.", "protein": "IL-11R\u03b1/gp130", "relationship_type": "causal", "source_pmcid": "PMC12379731" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation modulates receptor signaling.", "mechanism": "TNFR mediates TNF-\u03b1 signaling, driving inflammation and bone loss; inhibitors reduce bone resorption.", "protein": "TNFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379731" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "IL-1R signaling promotes osteoclast activation and bone resorption.", "protein": "IL-1R", "relationship_type": "causal", "source_pmcid": "PMC12379731" }, { "confidence": "medium", "disease": "Ankylosing spondylitis", "glycan_involvement": "N-glycosylation affects receptor-ligand interaction.", "mechanism": "IL-17RA mediates IL-17 signaling, promoting inflammation and bone loss; inhibitors improve bone outcomes.", "protein": "IL-17RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379731" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "SOST inhibits Wnt/\u03b2-catenin signaling, suppressing osteoblast activity and bone formation.", "protein": "Sclerostin (SOST)", "relationship_type": "causal", "source_pmcid": "PMC12379731" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates protein stability.", "mechanism": "DKK-1 inhibits Wnt signaling, reducing osteoblast differentiation and bone formation.", "protein": "DKK-1", "relationship_type": "causal", "source_pmcid": "PMC12379731" }, { "confidence": "medium", "disease": "Bone metastasis", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "IL-6R/gp130 signaling promotes tumor-induced bone destruction; blockade reduces metastasis.", "protein": "IL-6R/gp130", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379731" }, { "confidence": "high", "disease": "Cerebral amyloid angiopathy (CAA)", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and amyloid-\u03b2 production.", "mechanism": "Amyloid-\u03b2 derived from APP accumulates in cortical and leptomeningeal vessels, causing vessel fragility.", "protein": "Amyloid-\u03b2 precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12379837" }, { "confidence": "medium", "disease": "Spontaneous subdural hematoma (SDH)", "glycan_involvement": "Glycosylation of APP modulates amyloid-\u03b2 generation and vascular deposition.", "mechanism": "CAA (due to amyloid-\u03b2 deposition) increases risk of spontaneous SDH by weakening vessel walls.", "protein": "Amyloid-\u03b2 precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12379837" }, { "confidence": "medium", "disease": "Postoperative nausea and vomiting (PONV)", "glycan_involvement": "Glycocalyx integrity depends on glycosylation; protection prevents glycan shedding.", "mechanism": "Colloid infusion preserves endothelial glycocalyx thickness, reducing vascular permeability and intestinal edema, thereby lowering PONV risk.", "protein": "Endothelial glycocalyx", "relationship_type": "protective", "source_pmcid": "PMC12379978" }, { "confidence": "medium", "disease": "Vascular permeability/inflammation", "glycan_involvement": "Enzymatic cleavage of glycan chains disrupts barrier function.", "mechanism": "Increased activity leads to glycocalyx shedding, raising vascular permeability during inflammation.", "protein": "Glycocalyx-degrading enzymes", "relationship_type": "causal", "source_pmcid": "PMC12379978" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Synthetic glycan structure may interact with renal glycoproteins.", "mechanism": "HES may increase risk of AKI, especially in sepsis/critical illness, by affecting renal microvasculature.", "protein": "Hydroxyethyl starch (HES)", "relationship_type": "causal", "source_pmcid": "PMC12379978" }, { "confidence": "medium", "disease": "Intestinal edema", "glycan_involvement": "Albumin glycosylation affects its stability and osmotic function.", "mechanism": "Low albumin post-hepatectomy reduces colloid osmotic pressure, increasing risk of fluid extravasation and edema.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective", "source_pmcid": "PMC12379978" }, { "confidence": "low", "disease": "Intestinal bacterial translocation", "glycan_involvement": "Glycan-rich layer forms physical barrier.", "mechanism": "Glycocalyx integrity prevents edema and barrier breakdown, reducing bacterial translocation.", "protein": "Endothelial glycocalyx", "relationship_type": "protective", "source_pmcid": "PMC12379978" }, { "confidence": "low", "disease": "Delayed postoperative recovery", "glycan_involvement": "Glycan-like structure affects fluid distribution.", "mechanism": "Potential for increased interstitial fluid accumulation may delay recovery.", "protein": "Hydroxyethyl starch (HES)", "relationship_type": "causal", "source_pmcid": "PMC12379978" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation status may affect clearance.", "mechanism": "Elevated creatinine indicates renal dysfunction postoperatively.", "protein": "Serum creatinine", "relationship_type": "biomarker", "source_pmcid": "PMC12379978" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Indirect; not a glycoprotein but measured alongside glycoprotein markers.", "mechanism": "Elevated BUN reflects impaired renal function.", "protein": "Blood urea nitrogen (BUN)", "relationship_type": "biomarker", "source_pmcid": "PMC12379978" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT signals hepatocellular injury post-hepatectomy.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12379978" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Elevated AST indicates liver cell damage.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12379978" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "IL-2R\u03b1 is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Upregulated IL-2R\u03b1 expression in HCC tissues correlates with poor overall survival and increased immunosuppression.", "protein": "IL-2R\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Shedding of glycosylated IL-2R\u03b1 produces sIL-2R\u03b1; glycosylation affects its release and detection.", "mechanism": "Elevated serum sIL-2R\u03b1 correlates with increased Tregs and TSGF, indicating immune suppression and tumor progression.", "protein": "sIL-2R\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may influence receptor-ligand interactions and therapeutic antibody binding.", "mechanism": "IL-2R\u03b1 is implicated in immune regulation within the HCC tumor microenvironment; targeting may modulate Treg-mediated immunosuppression.", "protein": "IL-2R\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation required for proper cell surface expression and signaling.", "mechanism": "Downregulated in HCC; higher IL-2R\u03b2 expression is associated with better prognosis, possibly due to its role in NK and CD8+ T cell activation.", "protein": "IL-2R\u03b2", "relationship_type": "protective", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation important for receptor assembly and function.", "mechanism": "Upregulated in HCC tissues; included in prognostic risk model, but not independently predictive of survival.", "protein": "IL-2R\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Papillary thyroid cancer", "glycan_involvement": "Glycosylation affects stability and serum detection.", "mechanism": "Elevated sIL-2R\u03b1 predicts poor prognosis.", "protein": "sIL-2R\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation influences release and detection.", "mechanism": "High sIL-2R\u03b1 levels associated with poor prognosis.", "protein": "sIL-2R\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation impacts serum levels.", "mechanism": "Elevated sIL-2R\u03b1 correlates with poor prognosis.", "protein": "sIL-2R\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Aberrant expression of IL-2R\u03b1 is associated with autoimmune disease occurrence.", "protein": "IL-2R\u03b1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12379987" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "TSGF contains glycan components; glycosylation is part of its structure and function.", "mechanism": "Elevated TSGF in serum reflects tumor growth and angiogenesis; correlates with sIL-2R\u03b1.", "protein": "TSGF", "relationship_type": "biomarker", "source_pmcid": "PMC12379987" }, { "confidence": "high", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "HDL-associated glycoproteins (e.g., PON1, MPO) modulate function via glycosylation.", "mechanism": "HDL suppresses monocyte activation and pro-inflammatory cytokine production, reducing uric acid levels.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation affects PON1 stability and activity.", "mechanism": "PON1 exerts antioxidant effects, protecting HDL function and reducing CVD risk.", "protein": "Paraoxonase-1 (PON1)", "relationship_type": "protective", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation modulates MPO secretion and activity.", "mechanism": "MPO generates reactive species that impair HDL function, promoting CVD.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "causal", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "Glycosylation required for TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes vascular endothelial damage and hyperinsulinemia, increasing uric acid reabsorption.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "N-glycosylation modulates IL-6 stability and signaling.", "mechanism": "IL-6 produced by monocytes increases inflammation and uric acid levels.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "Glycosylation affects IL-10 secretion and activity.", "mechanism": "IL-10 is anti-inflammatory; reduced levels in HUA promote inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "protective", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "TLRs are glycoproteins; glycosylation essential for ligand recognition.", "mechanism": "SUA inhibits TLR signaling in monocytes, impairing migration and immune response.", "protein": "Toll-like receptor (TLR)", "relationship_type": "causal", "source_pmcid": "PMC12379993" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "HDL glycoproteins modulate renal protective effects.", "mechanism": "HDL function protects against lipid accumulation and oxidative stress in renal tissue.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12379993" }, { "confidence": "high", "disease": "Hyperuricemia (HUA)", "glycan_involvement": "Monocyte surface glycoproteins mediate cytokine secretion and migration.", "mechanism": "Monocytes produce pro-inflammatory cytokines that increase uric acid levels.", "protein": "Monocyte", "relationship_type": "causal", "source_pmcid": "PMC12379993" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "HDL glycoproteins influence anti-inflammatory properties.", "mechanism": "HDL-C levels and MHR are predictive of T2DM risk via inflammation and insulin resistance.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12379993" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Not specified", "mechanism": "GPX4 inhibits neuronal ferroptosis and reduces oxidative stress after stroke, promoting recovery.", "protein": "Glutathione Peroxidase 4 (GPX4)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "medium", "disease": "Ischemic Stroke", "glycan_involvement": "Not specified", "mechanism": "SelS gene mutations increase stroke risk by upregulating inflammatory markers.", "protein": "Selenoprotein S (SelS)", "relationship_type": "causal", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "Not specified", "mechanism": "GPX1 deletion increases neuronal injury and infarct size; GPX1 activity is neuroprotective.", "protein": "Glutathione Peroxidase 1 (GPX1)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "SelP is a glycoprotein; glycosylation may affect stability and transport.", "mechanism": "SelP interacts with Tau and \u03b1-tubulin, preserves microtubule structure, and reduces ROS burden.", "protein": "Selenoprotein P (SelP)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Not specified", "mechanism": "SelK enhances microglial A\u03b2 phagocytosis via CD36 palmitoylation, attenuating AD progression.", "protein": "Selenoprotein K (SelK)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Not specified", "mechanism": "GPX4 prevents ferroptosis and lipid peroxidation in dopaminergic neurons; loss leads to neurodegeneration.", "protein": "Glutathione Peroxidase 4 (GPX4)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "Not specified", "mechanism": "GPX1 deficiency increases dopamine depletion and oxidative damage in PD models.", "protein": "Glutathione Peroxidase 1 (GPX1)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "medium", "disease": "Huntington's Disease", "glycan_involvement": "Not specified", "mechanism": "GPX6 genetically interacts with mutant Huntingtin; overexpression reduces toxicity and neuronal death.", "protein": "Glutathione Peroxidase 6 (GPX6)", "protein_enriched": { "function": "", "gene_name": "PRR36", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H6K5" }, "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "medium", "disease": "Spinal Cord Injury", "glycan_involvement": "SelP glycosylation may affect receptor binding and transport.", "mechanism": "SelP transports Se to the brain, upregulates selenoproteins, and improves neuroinflammation and BBB integrity.", "protein": "Selenoprotein P (SelP)", "relationship_type": "protective", "source_pmcid": "PMC12380074" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Not specified", "mechanism": "GPX1 expression is increased in epileptic brain tissue, indicating enhanced antioxidant defense.", "protein": "Glutathione Peroxidase 1 (GPX1)", "relationship_type": "biomarker", "source_pmcid": "PMC12380074" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not directly discussed; sEVs are enriched in glycoproteins.", "mechanism": "USP10 delivered via MSC-sEVs stabilizes KLF4, reprograms macrophages to anti-fibrotic phenotype, reduces inflammation and fibrosis.", "protein": "USP10", "protein_enriched": { "function": "Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as ", "gene_name": "USP10", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14694" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380376" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Not specified.", "mechanism": "KLF4 stabilization by USP10 promotes anti-inflammatory macrophage polarization and upregulates MMP12 for tissue repair.", "protein": "KLF4", "protein_enriched": { "function": "Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates th", "gene_name": "KLF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O43474" }, "relationship_type": "protective", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "MMPs are glycoproteins; glycosylation may affect secretion/activity.", "mechanism": "MMP12 expression in macrophages is upregulated by KLF4, contributing to matrix remodeling and fibrosis resolution.", "protein": "MMP12", "protein_enriched": { "function": "May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic", "gene_name": "MMP12", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P39900" }, "relationship_type": "protective", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CD9 is a glycoprotein; glycosylation may affect sEV formation.", "mechanism": "CD9 is a marker of MSC-sEVs used for delivery of therapeutic cargo to liver macrophages.", "protein": "CD9", "protein_enriched": { "function": "Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:14575715, PubMed:1854", "gene_name": "CD9", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21926" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CD81 is a glycoprotein; glycosylation may influence sEV targeting.", "mechanism": "CD81 marks MSC-sEVs, facilitating their uptake by liver macrophages.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TSG101 is a glycoprotein; glycosylation may affect vesicle sorting.", "mechanism": "TSG101 is an sEV marker, indicating successful isolation of therapeutic vesicles.", "protein": "TSG101", "protein_enriched": { "function": "Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicu", "gene_name": "TSG101", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99816" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CD206 is a C-type lectin glycoprotein; glycosylation critical for ligand binding.", "mechanism": "CD206 marks anti-inflammatory macrophages induced by MSC-sEVs, associated with fibrosis resolution.", "protein": "CD206 (MRC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Arg1 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Arg1 upregulation in macrophages indicates anti-inflammatory phenotype after MSC-sEV treatment.", "protein": "Arg1", "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "iNOS is glycosylated; glycosylation may regulate activity.", "mechanism": "iNOS downregulation in macrophages reflects reduced inflammation after MSC-sEV therapy.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "low", "disease": "Liver fibrosis", "glycan_involvement": "Calnexin is a glycoprotein chaperone; glycosylation affects ER function.", "mechanism": "Calnexin is used as a negative control for sEV purity; not present in sEVs.", "protein": "Calnexin", "relationship_type": "biomarker", "source_pmcid": "PMC12380376" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "NT-proBNP is N-glycosylated, affecting its stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and is used for ADHF diagnosis and prognosis.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Cell surface glycoproteins mediate adhesion and activation.", "mechanism": "Activated neutrophils release proteolytic enzymes, degrade cardiac matrix, and induce cardiomyocyte apoptosis.", "protein": "Neutrophil", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Surface glycoproteins regulate migration and inflammatory signaling.", "mechanism": "Monocytes promote myocardial remodeling, fibrosis, and cell death.", "protein": "Monocyte", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycoproteins on lymphocyte surfaces mediate immune interactions.", "mechanism": "Lymphocyte depletion (lymphopenia) is associated with poor prognosis; lymphocytes regulate anti-inflammatory responses.", "protein": "Lymphocyte", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Platelet glycoproteins (e.g., GPIIb/IIIa) mediate aggregation and signaling.", "mechanism": "Platelet activation contributes to vascular dysfunction and chemokine regulation, driving HF progression.", "protein": "Platelet (PLT)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12380547" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycosylation modulates TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 upregulated by neurohormonal activation, promotes inflammation and myocardial injury.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12380547" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycosylation affects MCP-1 stability and chemotactic activity.", "mechanism": "MCP-1 recruits monocytes, amplifying cardiac inflammation.", "protein": "MCP-1", "relationship_type": "causal", "source_pmcid": "PMC12380547" }, { "confidence": "medium", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Glycosylation of RAAS hormones affects receptor interactions.", "mechanism": "RAAS activation modulates immune cell phenotypes and promotes inflammation.", "protein": "RAAS components", "relationship_type": "causal", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Acute Decompensated Heart Failure (ADHF)", "glycan_involvement": "Reflects glycoprotein-mediated immune cell activity.", "mechanism": "AISI integrates neutrophil, monocyte, platelet, and lymphocyte counts; both high and low AISI predict increased 30-day mortality.", "protein": "Aggregate Index of Systemic Inflammation (AISI)", "relationship_type": "biomarker", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "N-glycosylation affects NT-proBNP half-life and detection.", "mechanism": "NT-proBNP is a standard marker for HF diagnosis and prognosis.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380547" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Altered glycosylation may affect cell adhesion and metastatic potential.", "mechanism": "Promoter hypermethylation leads to E-cadherin silencing, associated with aggressive tumor phenotype.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380548" }, { "confidence": "high", "disease": "Chemoresistance in breast cancer", "glycan_involvement": "Glycosylation affects P-gp stability and drug efflux function.", "mechanism": "Curcumin reverses drug resistance by modulating ABCB1/MDR1 expression via epigenetic changes.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may influence BRCA1 stability and DNA repair activity.", "mechanism": "Promoter hypermethylation silences BRCA1; curcumin and resveratrol restore expression via epigenetic modulation.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect SNCG secretion and oncogenic signaling.", "mechanism": "Curcumin induces promoter hypermethylation, suppressing SNCG expression in ER+/PR+ cells.", "protein": "SNCG (Synuclein gamma)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Indirect; PRMT5 methylation may affect glycoprotein gene expression.", "mechanism": "Curcumin downregulates PRMT5 and its cofactor MEP50, reducing histone methylation and tumor progression.", "protein": "PRMT5", "protein_enriched": { "function": "Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356", "gene_name": "PRMT5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O14744" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may modulate GSTP1 enzymatic activity.", "mechanism": "Curcumin reverses GSTP1 promoter hypermethylation, restoring tumor suppressor function.", "protein": "GSTP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect ATP2A3 localization and function.", "mechanism": "Resveratrol upregulates ATP2A3 via reduced HDAC2 binding and increased histone acetylation, promoting apoptosis.", "protein": "ATP2A3", "protein_enriched": { "function": "The small GTPases Rab are key regulators in vesicle trafficking (PubMed:24788816). Essential for maintaining the integrity of the endosome-trans-Golgi network structure (By similarity). Together with ", "gene_name": "RAB29", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14966" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for IL15 secretion and receptor binding.", "mechanism": "Quercetin increases IL15 promoter methylation, reducing IL15 expression and cancer cell proliferation.", "protein": "IL15", "relationship_type": "causal", "source_pmcid": "PMC12380548" }, { "confidence": "medium", "disease": "Chemoresistance in breast cancer", "glycan_involvement": "FN1 glycosylation modulates ECM interactions and drug resistance.", "mechanism": "miR-222 upregulation suppresses PTEN and activates FN1, promoting drug resistance; EV-mediated miR-222 inhibition restores PTEN/FN1 signaling.", "protein": "FN1 (Fibronectin 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "high", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation may affect BRCA1 protein stability.", "mechanism": "Curcumin reactivates BRCA1 expression in TNBC by reducing promoter methylation.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380548" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza (HPAI) H5N1 infection", "glycan_involvement": "Binds \u03b12,3- and \u03b12,6-linked sialic acids; glycosylation affects receptor specificity", "mechanism": "Mediates viral entry via binding to sialic acid receptors; mutations enhance mammalian adaptation", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza (HPAI) H5N1 infection", "glycan_involvement": "Glycosylation modulates enzymatic activity and immune evasion", "mechanism": "Cleaves sialic acids to facilitate viral release; N1 subtype implicated in cross-species transmission", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "high", "disease": "Swine Influenza", "glycan_involvement": "Receptor binding specificity determined by glycan linkages", "mechanism": "HA mutations (e.g., D252Y, S136N) enhance binding to swine \u03b12,6-linked sialic acid receptors", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "medium", "disease": "Swine Influenza", "glycan_involvement": "Antibody recognition influenced by NA glycosylation", "mechanism": "Pre-existing N1-reactive antibodies (from prior H1N1 exposure/vaccination) may confer partial protection", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12380550" }, { "confidence": "high", "disease": "Human Influenza", "glycan_involvement": "Glycosylation affects immune recognition and host range", "mechanism": "HA mediates zoonotic transmission; mutations increase human receptor binding", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "medium", "disease": "Human Influenza", "glycan_involvement": "Glycosylation impacts antigenicity and antibody binding", "mechanism": "NA-inhibitory antibodies (from pandemic H1N1) may reduce H5N1 infection risk", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12380550" }, { "confidence": "medium", "disease": "Neurological disease in mammals (HPAI-associated)", "glycan_involvement": "Altered glycan binding enables extra-respiratory tissue tropism", "mechanism": "HA mutations linked to neurotropism and systemic spread in mammals (e.g., cats, minks)", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "medium", "disease": "Highly Pathogenic Avian Influenza (HPAI) H5N1 infection", "glycan_involvement": "Indirect; not a glycoprotein but interacts with glycosylated viral envelope", "mechanism": "MP mutations contribute to host adaptation and virulence", "protein": "Matrix protein (MP)", "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza (HPAI) H5N1 infection", "glycan_involvement": "Indirect; facilitates adaptation to glycan environment of mammalian cells", "mechanism": "PB2 mutations (e.g., E627K, D701N) enhance replication in mammals", "protein": "Polymerase basic protein 2 (PB2)", "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "medium", "disease": "Milk production impairment in dairy cattle", "glycan_involvement": "Sialidase activity targets glycan-rich mammary epithelium", "mechanism": "NA activity facilitates viral replication in mammary tissue, leading to impaired milk production", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12380550" }, { "confidence": "high", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation required for cell surface expression and ligand binding.", "mechanism": "TREM1 amplifies inflammatory responses; its inhibition by exercise may reduce inflammation and improve immune surveillance in ALL.", "protein": "TREM1", "protein_enriched": { "function": "Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses (PubMed:10799849, PubMed:21393102). Upon activation by various ligands such as PGL", "gene_name": "TREM1", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9NP99" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380555" }, { "confidence": "high", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Secreted glycoprotein; glycosylation affects stability and immune interactions.", "mechanism": "S100A8 promotes inflammation and leukemic progression; exercise-induced downregulation may reduce disease activity.", "protein": "S100A8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380555" }, { "confidence": "high", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Secreted glycoprotein; glycosylation modulates immune signaling.", "mechanism": "S100A9 is linked to inflammation and treatment resistance; exercise reduces its expression in NK cells.", "protein": "S100A9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Secreted glycoprotein; glycosylation influences receptor interactions.", "mechanism": "S100A12 is a pro-inflammatory mediator; exercise lowers its expression, potentially reducing ALL-associated inflammation.", "protein": "S100A12", "protein_enriched": { "function": "Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does n", "gene_name": "S100A13", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99584" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "IL1B expression predicts relapse in ALL; exercise reduces IL1B in NK cells, possibly lowering relapse risk.", "protein": "IL1B", "relationship_type": "biomarker", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Altered IL3RA expression impairs NK cell response to IL-2, contributing to immune dysfunction in ALL.", "protein": "IL3RA", "relationship_type": "causal", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor binding.", "mechanism": "IL4 interacts with glucocorticoid signaling, suppressing NK cell function in ALL.", "protein": "IL4", "protein_enriched": { "function": "Cytokine secreted primarily by mast cells, T-cells, eosinophils, and basophils that plays a role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-ce", "gene_name": "IL4", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05112" }, "relationship_type": "causal", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "O-glycosylation regulates ligand binding and immune checkpoint function.", "mechanism": "Differential HAVCR2 expression in NK cells may reflect immune exhaustion in ALL.", "protein": "HAVCR2 (TIM-3)", "relationship_type": "biomarker", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "N-glycosylation essential for MHC class II stability and peptide presentation.", "mechanism": "Altered HLA-DQA1 expression affects antigen presentation and immune surveillance in ALL.", "protein": "HLA-DQA1", "relationship_type": "biomarker", "source_pmcid": "PMC12380555" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "IFNLR1 signaling modulates NK cell activation; altered expression may impair anti-tumor immunity in ALL.", "protein": "IFNLR1", "protein_enriched": { "function": "Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeri", "gene_name": "IFNL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IZJ0" }, "relationship_type": "causal", "source_pmcid": "PMC12380555" }, { "confidence": "high", "disease": "Autoimmune Cerebellar Ataxia (ACA)", "glycan_involvement": "Not directly discussed; Homer-3 is a scaffold glycoprotein, possible glycosylation may affect antibody recognition.", "mechanism": "Autoantibodies against Homer-3 disrupt Purkinje cell calcium signaling, leading to cerebellar dysfunction.", "protein": "Homer-3", "protein_enriched": { "function": "Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated IT", "gene_name": "HOMER3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSC5" }, "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "medium", "disease": "Multiple System Atrophy, Cerebellar type (MSA-C)", "glycan_involvement": "Not specified.", "mechanism": "Homer-3 antibodies can mimic MSA-C clinically, but are absent in true MSA-C; useful for differential diagnosis.", "protein": "Homer-3", "protein_enriched": { "function": "Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated IT", "gene_name": "HOMER3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSC5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380574" }, { "confidence": "medium", "disease": "Progressive Supranuclear Palsy, Cerebellar type (PSP-C)", "glycan_involvement": "Not specified.", "mechanism": "Homer-3 antibody-positive ACA can mimic PSP-C; antibody testing aids in distinguishing ACA from PSP-C.", "protein": "Homer-3", "protein_enriched": { "function": "Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated IT", "gene_name": "HOMER3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSC5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380574" }, { "confidence": "low", "disease": "Alzheimer's Disease (AD)", "glycan_involvement": "Not specified.", "mechanism": "Rare cases of Homer-3 antibody-positive ACA present with cognitive/affective symptoms resembling AD.", "protein": "Homer-3", "protein_enriched": { "function": "Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated IT", "gene_name": "HOMER3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSC5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380574" }, { "confidence": "medium", "disease": "Paraneoplastic Cerebellar Syndrome", "glycan_involvement": "ITPR1 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-ITPR1 antibodies target cerebellar Purkinje cells, often associated with neoplastic processes.", "protein": "ITPR1", "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "medium", "disease": "Paraneoplastic Cerebellar Syndrome", "glycan_involvement": "Not specified.", "mechanism": "Anti-ARHGAP26 antibodies linked to cerebellar syndrome and underlying tumors.", "protein": "ARHGAP26", "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "high", "disease": "Chronic Gait Disturbance/Neuropathy", "glycan_involvement": "MAG is a heavily glycosylated protein; glycan epitopes are immunogenic.", "mechanism": "Anti-MAG antibodies cause neuropathy and gait disturbance via central nervous system involvement.", "protein": "MAG", "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "medium", "disease": "Spinocerebellar Ataxia type 7 (SCA7)", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect plasma levels.", "mechanism": "Elevated plasma GFAP differentiates SCA7 from MSA-C; associated with cerebellar degeneration.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380574" }, { "confidence": "high", "disease": "Tauopathy (IgLON5 disease)", "glycan_involvement": "IgLON5 is a cell adhesion glycoprotein; glycosylation may influence antibody binding.", "mechanism": "Anti-IgLON5 antibodies induce tau accumulation and synaptic dysfunction, leading to neurodegeneration.", "protein": "IgLON5", "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "high", "disease": "Autoimmune Cerebellar Ataxia (ACA)", "glycan_involvement": "mGluR1 is glycosylated; glycan structures may affect immunogenicity.", "mechanism": "Anti-mGluR1 antibodies disrupt glutamate signaling in Purkinje cells, causing ataxia.", "protein": "mGluR1", "relationship_type": "causal", "source_pmcid": "PMC12380574" }, { "confidence": "high", "disease": "immune-related adverse events (irAEs)", "glycan_involvement": "CTLA-4 is a glycoprotein; glycosylation affects its cell surface expression and immune regulation.", "mechanism": "Blockade of CTLA-4 by monoclonal antibodies disrupts immune tolerance, leading to multisystem irAEs.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "high", "disease": "immune-related adverse events (irAEs)", "glycan_involvement": "PD-1 glycosylation modulates ligand binding and immune signaling.", "mechanism": "PD-1 blockade enhances T-cell activation, increasing risk of autoimmune toxicities.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "high", "disease": "immune-related adverse events (irAEs)", "glycan_involvement": "PD-L1 glycosylation regulates its stability and immune inhibitory function.", "mechanism": "PD-L1 inhibition removes suppression of T-cell responses, triggering irAEs.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "myocarditis", "glycan_involvement": "Glycosylation of PD-1 may affect its immune regulatory role in cardiac tissue.", "mechanism": "PD-1 blockade can lead to T-cell mediated cardiac inflammation.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "high", "disease": "colitis/diarrhea", "glycan_involvement": "Glycosylation influences CTLA-4 trafficking and immune checkpoint function in gut.", "mechanism": "CTLA-4 inhibition increases gut immune activation, leading to colitis.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "thyroiditis", "glycan_involvement": "PD-1 glycosylation may modulate its interaction with thyroid tissue.", "mechanism": "PD-1 blockade disrupts tolerance to thyroid antigens, causing thyroiditis.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "pneumonitis/interstitial lung disease", "glycan_involvement": "PD-L1 glycosylation affects its immune suppressive function in lung tissue.", "mechanism": "PD-L1 inhibition can trigger immune-mediated lung injury.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "hepatitis/hepatobiliary disorders", "glycan_involvement": "Glycosylation modulates CTLA-4 function in liver immune homeostasis.", "mechanism": "CTLA-4 blockade increases hepatic immune activation, leading to hepatitis.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "nephritis/acute kidney injury", "glycan_involvement": "PD-1 glycosylation may influence renal immune responses.", "mechanism": "PD-1 inhibition can cause immune-mediated renal inflammation.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "medium", "disease": "maculopapular rash", "glycan_involvement": "PD-L1 glycosylation affects its stability and immune modulation in skin.", "mechanism": "PD-L1 blockade can induce cutaneous immune activation.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal", "source_pmcid": "PMC12380579" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and secretion.", "mechanism": "Elevated serum IL-6 is associated with acute inflammation and severity in KD, especially in KD shock syndrome.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates IL-6 bioactivity and half-life.", "mechanism": "Serum and CSF IL-6 are elevated in MERS, reflecting systemic inflammatory response.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "IL-18 glycosylation influences secretion and receptor binding.", "mechanism": "Serum IL-18 is variably elevated in KD; lower elevation compared to IL-6 may help differentiate KD from other inflammatory diseases.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation is essential for sTNF-RII stability and function.", "mechanism": "Elevated sTNF-RII reflects TNF pathway activation in KD.", "protein": "Soluble TNF Receptor Type II (sTNF-RII)", "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "Kawasaki disease", "glycan_involvement": "Glycosylation affects CXCL9 secretion and chemotactic activity.", "mechanism": "CXCL9 is highly elevated in KD, indicating Th1-type immune activation.", "protein": "C-X-C motif chemokine ligand 9 (CXCL9)", "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "high", "disease": "Kawasaki disease", "glycan_involvement": "IVIG Fc glycosylation modulates anti-inflammatory efficacy.", "mechanism": "IVIG is used to treat KD and prevent coronary artery complications.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Fc glycosylation impacts IVIG immunomodulatory properties.", "mechanism": "IVIG is used to treat MERS-associated neurological symptoms.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380580" }, { "confidence": "medium", "disease": "Coronary artery abnormality (CAA)", "glycan_involvement": "Glycosylation affects IL-6 receptor interactions in vascular inflammation.", "mechanism": "High IL-6 levels are linked to increased risk of CAA in KD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12380580" }, { "confidence": "low", "disease": "MERS", "glycan_involvement": "Glycosylation required for sTNF-RII function.", "mechanism": "Elevated sTNF-RII in MERS reflects systemic inflammation.", "protein": "Soluble TNF Receptor Type II (sTNF-RII)", "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "low", "disease": "MERS", "glycan_involvement": "Glycosylation modulates CXCL9 activity.", "mechanism": "CXCL9 elevation in MERS indicates immune activation.", "protein": "C-X-C motif chemokine ligand 9 (CXCL9)", "relationship_type": "biomarker", "source_pmcid": "PMC12380580" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "APP is a heavily glycosylated protein; glycosylation affects its processing and cellular localization.", "mechanism": "Upregulated in vascular tissues under hyperglycemia, contributing to cellular stress and apoptosis.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380672" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation modulates APP stability and cell signaling in tumor progression.", "mechanism": "Overexpression correlates with poor survival, increased proliferation, and invasion via PI3K/AKT and Notch pathways.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380672" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation may regulate NLRP3 inflammasome assembly and secretion.", "mechanism": "Chronic activation drives systemic inflammation and insulin resistance.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12380672" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation may affect NLRP3 stability and inflammatory signaling.", "mechanism": "Promotes proliferation, EMT, and metastasis via NF-\u03baB/STAT3 signaling.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "N-glycosylation influences CYP2C19 folding and enzymatic activity.", "mechanism": "Diabetes suppresses CYP2C19 activity, impairing drug metabolism and increasing oxidative stress.", "protein": "CYP2C19", "relationship_type": "biomarker", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation may modulate CYP2C19 drug metabolism in tumor cells.", "mechanism": "Polymorphisms increase cancer risk and reduce chemotherapy efficacy.", "protein": "CYP2C19", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Interacts with glycoproteins affecting chromatin and transcriptional regulation.", "mechanism": "Overexpressed in diabetic complications, promotes fibrosis and oxidative stress.", "protein": "PVT1", "relationship_type": "causal", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "May regulate glycoprotein expression involved in cell cycle and signaling.", "mechanism": "Acts as oncogene, stabilizes MYC, suppresses tumor suppressors, drives proliferation and therapy resistance.", "protein": "PVT1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation affects SRC localization and kinase activity.", "mechanism": "Central hub in PPI network, regulates proliferation and invasion.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380672" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation may regulate CASP3 activation and apoptotic signaling.", "mechanism": "Core hub in PPI network, mediates apoptosis and cell death.", "protein": "CASP3", "relationship_type": "biomarker", "source_pmcid": "PMC12380672" }, { "confidence": "high", "disease": "Anti-NMDAR encephalitis", "glycan_involvement": "NMDAR is a glycoprotein; glycosylation may affect antibody binding and receptor trafficking.", "mechanism": "IgG autoantibodies target the GluN1 subunit, disrupting glutamatergic signaling and causing neuropsychiatric symptoms.", "protein": "NMDAR", "relationship_type": "causal", "source_pmcid": "PMC12380692" }, { "confidence": "high", "disease": "GFAP astrocytopathy", "glycan_involvement": "GFAP is glycosylated; glycosylation may influence antigenicity.", "mechanism": "GFAP-IgG in CSF is a disease-specific biomarker; titer correlates with severity.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380692" }, { "confidence": "high", "disease": "Autoimmune encephalitis", "glycan_involvement": "Glycosylation of NMDAR may modulate immune recognition.", "mechanism": "Autoantibodies against NMDAR cause cognitive impairment and psychiatric symptoms.", "protein": "NMDAR", "relationship_type": "causal", "source_pmcid": "PMC12380692" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "Glycosylation may affect GFAP immunogenicity.", "mechanism": "Anti-GFAP antibodies indicate astrocytic involvement in AE.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380692" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "MOG is a glycoprotein; glycosylation is critical for antigenicity.", "mechanism": "Anti-MOG antibodies are detected in some AE cases.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC12380692" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "LGI1 is glycosylated; glycosylation may affect antibody binding.", "mechanism": "Anti-LGI1 antibodies define a subtype of AE.", "protein": "LGI1", "protein_enriched": { "function": "", "gene_name": "C1orf74", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96LT6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380692" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "CASPR2 glycosylation may influence immune recognition.", "mechanism": "Anti-CASPR2 antibodies are associated with AE.", "protein": "CASPR2", "relationship_type": "biomarker", "source_pmcid": "PMC12380692" }, { "confidence": "high", "disease": "Autoimmune encephalitis", "glycan_involvement": "CD20 is glycosylated; glycosylation may affect antibody binding.", "mechanism": "Targeted by ofatumumab to deplete B cells and reduce autoantibody production.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380692" }, { "confidence": "high", "disease": "Autoimmune encephalitis", "glycan_involvement": "FcRn is glycosylated; glycosylation affects IgG binding and recycling.", "mechanism": "Targeted by efgartigimod to accelerate pathogenic IgG clearance.", "protein": "FcRn", "protein_enriched": { "function": "May be implicated in B-cell differentiation and lymphomagenesis", "gene_name": "FCRLA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "Q7L513" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380692" }, { "confidence": "medium", "disease": "Paraneoplastic neurological syndrome", "glycan_involvement": "Glycosylation of NMDAR in teratoma may influence immune response.", "mechanism": "Ectopic NMDAR expression in teratomas triggers autoantibody production.", "protein": "NMDAR", "relationship_type": "causal", "source_pmcid": "PMC12380692" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor activation.", "mechanism": "Overexpressed in OSCC, drives proliferation, survival, and metastasis via MAPK and PI3K/Akt pathways.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380768" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation required for proper folding and signaling.", "mechanism": "Overexpression promotes proliferation, angiogenesis, and metastasis; interacts with EGFR for resistance.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380768" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances immune suppression.", "mechanism": "Upregulated via STAT3, mediates immune evasion by suppressing T-cell activity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "O-glycosylation affects ligand binding and cell migration.", "mechanism": "Cell surface marker for cancer stem cells, associated with invasion and metastasis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Promotes extracellular matrix degradation, invasion, and metastasis; upregulated by STAT3.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12380768" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation essential for receptor binding and angiogenic activity.", "mechanism": "Induced by STAT3, drives angiogenesis and correlates with poor prognosis.", "protein": "VEGF", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation modulates integrin function and cell adhesion.", "mechanism": "Marker for distant metastasis and prognosis.", "protein": "ITGB4", "relationship_type": "biomarker", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation affects integrin-mediated signaling.", "mechanism": "Associated with metastasis and poor prognosis.", "protein": "ITGA3", "protein_enriched": { "function": "Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma m", "gene_name": "ITGA3", "glycan_count": 98, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06247RL", "G07246CJ", "G13131HA", "G27058EU", "G30740WO", "G43223CG", "G45395BF", "G53075ES", "G57776ZS", "G60834IK", "G62765YT", "G68490OW", "G70232NH", "G70441OD", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G85282JO", "G86880BF", "G57321FI", "G49108TO", "G00912UN", "G02815KT", "G08918WF", "G10486CT", "G27947YN", "G31852PQ", "G41071NU", "G41247ZX", "G49906RN", "G59626AS", "G60033FS", "G65184UU", "G70619PT", "G72790NZ", "G83646BJ", "G87661QW", "G90659AW", "G99668VU", "G07755XJ", "G77547TA", "G47950XN", "G55132BD", "G72747WU", "G83633GK", "G85554PZ", "G06110VR", "G14669DU", "G28681TP", "G36442WJ", "G92050GC", "G37412TK", "G47702MW", "G04657PL", "G05049YU", "G05962QB", "G08290VR", "G10819WX", "G14972EH", "G16125XL", "G25079LO", "G27915IV", "G29545VG", "G30970QQ", "G35541EV", "G39471UU", "G40926MX", "G42124LM", "G47644PP", "G50856PC", "G51653BI", "G59324HL", "G64527OM", "G73291XG", "G75568BH", "G76295SF", "G80479JV", "G85677PP", "G92135MA", "G93718GY", "G98611JV", "G16407EV", "G25637MV", "G28541PG", "G37818NZ", "G43769HG", "G44753VC", "G46503DX", "G49755GI", "G57776ZU", "G70223PD", "G87123QX", "G70101JE", "G92406TI", "G01650EU", "G37399XV", "G95865ZB" ], "uniprot_id": "P26006" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation regulates cell-cell adhesion and stability.", "mechanism": "Downregulation promotes EMT and metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "causal", "source_pmcid": "PMC12380768" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "N-glycosylation influences adhesion and migration.", "mechanism": "Upregulation during EMT increases cell motility and invasion.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "causal", "source_pmcid": "PMC12380768" }, { "confidence": "high", "disease": "In-stent Thrombosis", "glycan_involvement": "Glycosylation is essential for IIb/IIIa function and ligand binding.", "mechanism": "Glycoprotein IIb/IIIa mediates platelet aggregation; inhibition reduces thrombosis risk after stenting.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "high", "disease": "In-stent Thrombosis", "glycan_involvement": "Targets glycosylated IIb/IIIa complex.", "mechanism": "Tirofiban inhibits glycoprotein IIb/IIIa, preventing platelet aggregation and reducing thrombosis risk.", "protein": "Tirofiban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "Inhibition of IIb/IIIa reduces platelet-mediated occlusion in AIS.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "medium", "disease": "Acute Ischemic Stroke (AIS)", "glycan_involvement": "Acts on glycosylated IIb/IIIa.", "mechanism": "Tirofiban used peri-procedurally to prevent thrombotic events during stenting in AIS.", "protein": "Tirofiban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "medium", "disease": "Carotid Artery Dissection (CAD)", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Platelet aggregation via IIb/IIIa contributes to thrombus formation in CAD.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "medium", "disease": "Carotid Artery Dissection (CAD)", "glycan_involvement": "Targets glycosylated IIb/IIIa.", "mechanism": "Tirofiban prevents platelet aggregation in CAD patients undergoing stenting.", "protein": "Tirofiban", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380769" }, { "confidence": "low", "disease": "Intracranial Hemorrhage (ICH)", "glycan_involvement": "Glycosylation affects receptor-ligand interactions.", "mechanism": "Inhibition may reduce risk of thrombotic complications but increases bleeding risk.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "protective", "source_pmcid": "PMC12380769" }, { "confidence": "low", "disease": "Intracranial Hemorrhage (ICH)", "glycan_involvement": "Acts on glycosylated IIb/IIIa.", "mechanism": "Tirofiban may be safe in select ICH patients post-stenting, but bleeding risk remains.", "protein": "Tirofiban", "relationship_type": "protective/risk", "source_pmcid": "PMC12380769" }, { "confidence": "high", "disease": "Chronic spinal cord injury (SCI)", "glycan_involvement": "Laminin is a glycoprotein; its glycosylation is essential for matrix assembly and cell interactions.", "mechanism": "Promotes axonal regeneration and functional recovery when provided exogenously in polymeric form.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "high", "disease": "Chronic spinal cord injury (SCI)", "glycan_involvement": "PolyLM retains glycosylation features of native laminin, crucial for bioactivity.", "mechanism": "Polymerized laminin (polylaminin) enhances axonal growth and improves gait function in chronic SCI.", "protein": "Polylaminin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "high", "disease": "Glial scar formation", "glycan_involvement": "Targets glycosaminoglycan chains on proteoglycans.", "mechanism": "Enzymatically digests chondroitin sulfate proteoglycans in glial scar, reducing inhibitory environment for axon regeneration.", "protein": "Chondroitinase ABC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "medium", "disease": "Chronic spinal cord injury (SCI)", "glycan_involvement": "GDNF is glycosylated, which affects its stability and secretion.", "mechanism": "Acts as a chemoattractant for regenerating axons, promoting functional recovery.", "protein": "Glial cell-derived neurotrophic factor (GDNF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "high", "disease": "Glial scar formation", "glycan_involvement": "Glycosaminoglycan chains are the inhibitory moiety.", "mechanism": "Major inhibitory molecules in glial scar that impede axonal regeneration.", "protein": "Chondroitin sulfate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC12380836" }, { "confidence": "medium", "disease": "Intervertebral disc degeneration (IVDD)", "glycan_involvement": "Glycosylation mediates cell-matrix interactions.", "mechanism": "Laminin-rich environments support axonal regeneration in peripheral nervous system; exogenous application may aid recovery in IVDD-induced SCI.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12380836" }, { "confidence": "medium", "disease": "Paralysis", "glycan_involvement": "Glycosylation required for polymeric structure and bioactivity.", "mechanism": "PolyLM administration associated with improved gait and partial reversal of paralysis in chronic SCI.", "protein": "Polylaminin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "high", "disease": "Chronic spinal cord injury (SCI)", "glycan_involvement": "Enzyme acts on glycosaminoglycan chains.", "mechanism": "Removes inhibitory chondroitin sulfate proteoglycans, facilitating axonal regrowth and functional recovery.", "protein": "Chondroitinase ABC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "medium", "disease": "Glial scar formation", "glycan_involvement": "Glycosylation mediates anti-inhibitory effects.", "mechanism": "Contact with laminin can render axons insensitive to inhibitory chondroitin sulfate proteoglycans.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12380836" }, { "confidence": "low", "disease": "Paralysis", "glycan_involvement": "Glycosylation affects GDNF bioactivity.", "mechanism": "GDNF promotes axonal attraction and may contribute to motor recovery.", "protein": "GDNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380836" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "Glycosylation required for function and serum stability", "mechanism": "Associated with prognosis of adverse outcomes in AIS patients", "protein": "mannose-binding lectin", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "high", "disease": "acute ischemic stroke", "glycan_involvement": "Minor N-glycosylation; not central to mechanism", "mechanism": "Low or high hemoglobin levels associated with increased risk of adverse outcomes after AIS (U-shaped relationship)", "protein": "hemoglobin", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "Glycosylation affects stability and detection", "mechanism": "Elevated levels associated with poor prognosis in AIS", "protein": "procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "low", "disease": "acute ischemic stroke", "glycan_involvement": "Glycosylation may affect secretion and function", "mechanism": "Associated with adverse outcomes in AIS", "protein": "adipocyte fatty acid binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "low", "disease": "acute ischemic stroke", "glycan_involvement": "N-glycosylation modulates half-life and activity", "mechanism": "Altered levels linked to stroke prognosis", "protein": "cortisol-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "Minor glycosylation; not central to mechanism", "mechanism": "Lower albumin associated with worse outcomes; may reflect nutritional/inflammatory status", "protein": "albumin", "relationship_type": "protective", "source_pmcid": "PMC12380848" }, { "confidence": "high", "disease": "thrombosis", "glycan_involvement": "N-glycosylation modulates clotting function", "mechanism": "High fibrinogen promotes thrombosis, contributing to stroke risk", "protein": "fibrinogen", "relationship_type": "causal", "source_pmcid": "PMC12380848" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "Glycosylation affects secretion and clearance", "mechanism": "Elevated levels predict poor prognosis in AIS", "protein": "natriuretic peptide", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "Glycosylation affects stability", "mechanism": "Higher levels associated with adverse outcomes", "protein": "copeptin", "relationship_type": "biomarker", "source_pmcid": "PMC12380848" }, { "confidence": "medium", "disease": "acute ischemic stroke", "glycan_involvement": "N-glycosylation of ApoB affects LDL metabolism", "mechanism": "Elevated LDL increases risk of atherosclerosis and stroke", "protein": "low-density lipoprotein (LDL)", "relationship_type": "risk factor", "source_pmcid": "PMC12380848" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Glycosylation critical for epitope recognition and function.", "mechanism": "Marks tumor-initiating cells (PaCSCs) with high self-renewal and chemoresistance; targeted by CAR-NK and antibody therapies.", "protein": "CD133", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380912" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Heavily glycosylated; glycan structures modulate ligand binding and CSC properties.", "mechanism": "Associated with increased proliferation, metastasis, and resistance; CD44v6 isoform linked to anti-angiogenic therapy resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation modulates cell adhesion and signaling.", "mechanism": "Essential for PaCSC survival and tumor growth.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Glycosylation affects ECM interactions and cell migration.", "mechanism": "Identifies aggressive PaCSC subpopulation; regulated by TGF-\u03b2/Smad pathway.", "protein": "LAMC2 (Laminin \u03b32)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Heavily glycosylated; sialylation modulates immune evasion.", "mechanism": "Enriched in PaCSCs after chemotherapy; associated with increased tumorigenicity.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Metastatic PDAC", "glycan_involvement": "Glycosylation may affect antigenicity and CAR-T recognition.", "mechanism": "CAR-T therapy targeting Claudin18.2 reduces ALDH1A1+ CSCs and tumor burden.", "protein": "Claudin18.2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380912" }, { "confidence": "low", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Predicted glycosylation may influence antibody binding.", "mechanism": "Radioimmunotherapy against DCLK1 targets CSC niches.", "protein": "DCLK1", "protein_enriched": { "function": "Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system", "gene_name": "DCLK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "O15075" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Glycosylation modulates SIRP\u03b1 binding and immune evasion.", "mechanism": "Anti-CD47 antibody therapy enhances macrophage-mediated phagocytosis of leukemic stem cells.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12380912" }, { "confidence": "high", "disease": "Chemoresistant PDAC", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Promotes stemness, ROS detoxification, and gemcitabine resistance in PaCSCs.", "protein": "ALDH1A1", "protein_enriched": { "function": "Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:1929640", "gene_name": "ALDH1A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00352" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12380912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "N-glycosylation modulates ligand binding and signaling.", "mechanism": "Surface marker for PaCSCs; involved in migration and metastasis.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "biomarker", "source_pmcid": "PMC12380912" }, { "confidence": "high", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation affects P-gp localization and function at the BBB.", "mechanism": "P-gp limits CNS drug entry and contributes to pharmacoresistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation modulates receptor binding and transport efficiency.", "mechanism": "Transferrin receptor-mediated transcytosis enables large molecule transport across BBB.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation required for receptor interaction and transport.", "mechanism": "Insulin crosses BBB via receptor-mediated transcytosis, influencing CNS metabolism.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation may affect tight junction assembly and stability.", "mechanism": "Claudin-5 regulates tight junction integrity; disruption increases BBB permeability.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC12381367" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation modulates tau aggregation and toxicity.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, driving neurodegeneration.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12381367" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences APP processing and plaque formation.", "mechanism": "APP cleavage produces beta-amyloid plaques, a hallmark of AD pathology.", "protein": "Beta-amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation essential for laminin polymerization and cell adhesion.", "mechanism": "Laminin supports basal lamina structure and BBB integrity.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Blood-brain barrier dysfunction", "glycan_involvement": "Glycosylation required for collagen fibril formation.", "mechanism": "Collagen maintains extracellular matrix and BBB stability.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12381367" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation affects transporter trafficking and activity.", "mechanism": "ABC transporters efflux anti-epileptic drugs, reducing CNS drug levels.", "protein": "ATP-binding cassette transporters", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381367" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation modulates receptor binding and transport.", "mechanism": "Lipoproteins cross BBB via receptor-mediated transcytosis; altered levels linked to stroke risk.", "protein": "Lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12381367" }, { "confidence": "high", "disease": "All-cause mortality in maintenance hemodialysis patients", "glycan_involvement": "N-glycosylation affects RBP4 stability and plasma half-life.", "mechanism": "Low plasma RBP4 levels are associated with increased risk of all-cause mortality; RBP4 reflects nutritional, inflammatory, and metabolic status.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Elevated RBP4 linked to CVD risk via effects on endothelial dysfunction and atherosclerosis.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "N-glycosylation modulates plasma levels.", "mechanism": "Elevated RBP4 associated with insulin resistance and T2DM; low RBP4 in dialysis patients linked to mortality.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation required for adipokine activity.", "mechanism": "RBP4 acts as an adipokine; elevated in obesity.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation affects secretion and activity.", "mechanism": "RBP4 impairs insulin signaling in animal models.", "protein": "Retinol-binding protein 4", "relationship_type": "causal", "source_pmcid": "PMC12381377" }, { "confidence": "high", "disease": "Chronic kidney disease", "glycan_involvement": "N-glycosylation influences renal filtration.", "mechanism": "Elevated RBP4 due to impaired renal clearance; marker of CKD progression.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation required for vascular transport.", "mechanism": "Altered RBP4 levels associated with clinical atherosclerosis.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "medium", "disease": "Sudden cardiac death", "glycan_involvement": "N-glycosylation affects plasma stability.", "mechanism": "Low RBP4 levels linked to increased risk in diabetic hemodialysis patients.", "protein": "Retinol-binding protein 4", "relationship_type": "biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "high", "disease": "All-cause mortality in maintenance hemodialysis patients", "glycan_involvement": "Glycosylation status influences albumin function and turnover.", "mechanism": "Low albumin is a marker of malnutrition and inflammation, associated with increased mortality; albumin indirectly affects mortality via RBP4.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12381377" }, { "confidence": "high", "disease": "Inflammation-related mortality", "glycan_involvement": "Glycosylation essential for CRP function.", "mechanism": "Elevated hs-CRP reflects systemic inflammation, associated with increased mortality and lower RBP4.", "protein": "High-sensitivity C-reactive protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12381377" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "MGAM glycosylation affects its enzymatic activity and stability; altered glycosylation may impact CRC progression.", "mechanism": "Downregulation and mutation of MGAM associated with CRC; MGAM is a direct target of alpha-glucosidase inhibitors (acarbose, voglibose) with potential for drug repurposing.", "protein": "MGAM", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12381534" }, { "confidence": "high", "disease": "Colorectal Cancer (CRC)", "glycan_involvement": "Likely glycosylated; glycan status may influence immune cell infiltration and tumor microenvironment.", "mechanism": "Upregulated in CRC and other GI cancers; combined MGAM/MGAM2 expression improves diagnostic accuracy (>80%).", "protein": "MGAM2", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "high", "disease": "Gastric Cancer", "glycan_involvement": "Altered glycosylation may affect MGAM function in gastric tissue.", "mechanism": "Decreased MGAM expression in intestinal-type gastric cancer; associated with carcinogenesis.", "protein": "MGAM", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "high", "disease": "Bladder Cancer", "glycan_involvement": "N-glycosylation pattern is directly used for biomarker detection.", "mechanism": "Distinct N-glycosylation pattern of MGAM serves as a biomarker for bladder cancer progression.", "protein": "MGAM", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Urinary glycoprotein profile used for non-invasive detection.", "mechanism": "MGAM glycoproteins uniquely expressed in urine of aggressive prostate cancer; higher expression in castration-resistant metastatic tumors.", "protein": "MGAM", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "medium", "disease": "Lung Adenocarcinoma (LUAD)", "glycan_involvement": "Glycosylation may affect MGAM's role in tumor progression.", "mechanism": "MGAM is a key mutated gene in LUAD; targeted by herbal formulas and associated with EGFR mutations.", "protein": "MGAM", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "medium", "disease": "Cutaneous Melanoma (SKCM)", "glycan_involvement": "Glycosylation status may modulate MGAM's function in melanoma.", "mechanism": "MGAM SNV mutations highly expressed in glycolytic subtype, associated with poor prognosis.", "protein": "MGAM", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "Amplified glycoprotein expression may alter cell surface properties.", "mechanism": "MGAM amplified and overexpressed (6.6-fold) in OSCC; identified as a drug development target.", "protein": "MGAM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381534" }, { "confidence": "medium", "disease": "Anal Canal Squamous Cell Carcinoma (ACSCC)", "glycan_involvement": "Glycosylation may affect mutation impact and protein stability.", "mechanism": "MGAM2 among top mutated genes in ACSCC.", "protein": "MGAM2", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (LIHC)", "glycan_involvement": "Glycosylation may modulate immune interactions.", "mechanism": "MGAM2 upregulated in LIHC; associated with immune cell infiltration and prognosis.", "protein": "MGAM2", "relationship_type": "biomarker", "source_pmcid": "PMC12381534" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "CD44 is a glycoprotein receptor for hyaluronic acid (HA), a glycosaminoglycan.", "mechanism": "HA-CD44 binding promotes cancer cell migration and invasion via cytoskeletal reorganization.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "high", "disease": "Cancer cell invasion", "glycan_involvement": "HA binding to glycosylated CD44 is required for signal initiation.", "mechanism": "Flexible HA binding to CD44 triggers signalling for invadopodia formation and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell dormancy", "glycan_involvement": "Notch-2 requires glycosylation for function and ligand interaction.", "mechanism": "Upregulation of Notch-2 in high-concentration HA induces quiescence/dormancy in glioblastoma cells.", "protein": "Notch-2", "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell dormancy", "glycan_involvement": "Nicastrin is a glycoprotein essential for gamma-secretase activity.", "mechanism": "Nicastrin (gamma-secretase subunit) is upregulated in dormant cells, mediating Notch and CD44 signalling.", "protein": "Nicastrin", "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell dormancy", "glycan_involvement": "SPARC is a secreted glycoprotein; glycosylation affects secretion and function.", "mechanism": "SPARC upregulated in dormant glioblastoma cells in high HA, modulating Notch pathway.", "protein": "SPARC (Osteonectin)", "relationship_type": "biomarker", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell dormancy", "glycan_involvement": "PROS1 is a glycoprotein; glycosylation required for secretion.", "mechanism": "PROS1 upregulated in dormant cells, regulates Notch signalling.", "protein": "PROS1 (Protein S)", "relationship_type": "biomarker", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell invasion", "glycan_involvement": "Indirect; interacts with glycosylated CD44.", "mechanism": "Links CD44 to actin cytoskeleton, facilitating invadopodia and migration.", "protein": "Moesin", "protein_enriched": { "function": "Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers a", "gene_name": "MSN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P26038" }, "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "low", "disease": "Glioblastoma", "glycan_involvement": "Binds hyaluronan, a glycosaminoglycan.", "mechanism": "Low expression in glioblastoma cells; involved in HA degradation and cell migration.", "protein": "CEMIP", "protein_enriched": { "function": "Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to ", "gene_name": "CEMIP", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G80920RR", "G31852PQ", "G49108TO" ], "uniprot_id": "Q8WUJ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell dormancy", "glycan_involvement": "ADAMs are glycoproteins; glycosylation affects activity.", "mechanism": "Upregulated in crosslinked HA, mediating Notch cleavage and signalling.", "protein": "ADAM proteases", "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "medium", "disease": "Cancer cell invasion", "glycan_involvement": "MMP2 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "Upregulated in flexible HA, promotes ECM degradation and invasion.", "protein": "MMP2", "relationship_type": "causal", "source_pmcid": "PMC12381586" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect stability and receptor binding.", "mechanism": "Enhances insulin sensitivity via AMPK activation, mTORC1 inhibition, anti-inflammatory and antioxidant effects.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation influences FGF21 half-life and activity.", "mechanism": "Improves glucose uptake, reduces blood glucose, protects \u03b2-cells from glucolipotoxicity.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation may modulate secretion and receptor interaction.", "mechanism": "Promotes adipose tissue browning, increases energy expenditure, reduces adiposity.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381644" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation status may affect systemic distribution.", "mechanism": "Reduces hyperinsulinemia and inflammation, improves lipid metabolism.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12381644" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect CNS penetration.", "mechanism": "Improves central insulin signaling, reduces neuroinflammation and oxidative stress.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "protective", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation impacts hepatic receptor binding.", "mechanism": "Promotes hepatic fat oxidation, reduces triglycerides and cholesterol.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Enhances insulin sensitivity in adipose and muscle tissue; FGF21 stimulates its secretion.", "protein": "Lipocalin (Adiponectin)", "relationship_type": "protective", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Glycosylation affects ligand binding and cell surface expression.", "mechanism": "Binds advanced glycation end products, triggers inflammation and \u03b2-cell apoptosis.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation of FGFR1/KLB modulates receptor function.", "mechanism": "FGF21 signals via FGFR1/KLB to activate downstream metabolic pathways.", "protein": "FGFR1/\u03b2-Klotho (KLB) complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381644" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation may regulate nuclear translocation and DNA binding.", "mechanism": "Promotes inflammation, inhibits insulin signaling via IRS1 phosphorylation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12381644" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Aberrant glycosylation increases immunogenicity and tumor specificity.", "mechanism": "Overexpressed on NSCLC cells; targeted by mRNA vaccines to induce immune response.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "high", "disease": "Prostate cancer (CRPC)", "glycan_involvement": "Tumor-associated glycoforms enhance antigenicity.", "mechanism": "Included in mRNA vaccine antigens for CRPC; induces immune response.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates receptor activity and immune recognition.", "mechanism": "Overexpressed and glycosylated in breast cancer; mRNA vaccines can target Her-2/Neu.", "protein": "Her-2/Neu (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Heavy glycosylation affects immune visibility.", "mechanism": "CEA is a classic glycoprotein biomarker and mRNA vaccine target in colorectal cancer.", "protein": "Carcinoembryonic antigen (CEA, CEACAM5)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect antigen processing/presentation.", "mechanism": "Expressed on melanoma cells; mRNA vaccines induce T-cell responses.", "protein": "Melan-A/MART-1", "protein_enriched": { "function": "Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the", "gene_name": "MLANA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16655" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Targeted by mRNA vaccines to stimulate immune response in melanoma.", "protein": "gp100 (PMEL)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects stability and immune recognition.", "mechanism": "Included in mRNA vaccine antigens for melanoma.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Potential glycosylation may affect immunogenicity.", "mechanism": "Cancer/testis antigen targeted by mRNA vaccines in melanoma.", "protein": "MAGE-A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may modulate cell surface expression.", "mechanism": "Targeted by CAR-T and mRNA vaccines in solid tumors including ovarian cancer.", "protein": "Claudin 6 (CLDN6)", "protein_enriched": { "function": "Plays a major role in tight junction-specific obliteration of the intercellular space", "gene_name": "CLDN6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P56747" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation may affect protein stability.", "mechanism": "Included in mRNA vaccine antigens; inhibits apoptosis in melanoma cells.", "protein": "Survivin (BIRC5)", "protein_enriched": { "function": "Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a c", "gene_name": "BIRC5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15392" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12381778" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect stability and antioxidant function.", "mechanism": "Higher serum albumin levels are inversely associated with NAFLD risk, possibly due to antioxidant properties and reflecting hepatic synthetic function.", "protein": "Serum Albumin", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "N-glycosylation may modulate albumin's stability and function.", "mechanism": "Lower albumin levels correlate with more severe NASH and fibrosis.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Altered glycosylation in cirrhosis may affect albumin half-life.", "mechanism": "Reduced albumin reflects impaired hepatic function and advanced liver disease.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "low", "disease": "Primary liver malignancy", "glycan_involvement": "Glycosylation changes may occur in malignancy.", "mechanism": "Low albumin is associated with poor prognosis in liver cancer.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation may affect renal clearance.", "mechanism": "Albumin levels are used to assess kidney function and proteinuria.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation may influence albumin's anti-inflammatory properties.", "mechanism": "Higher sACR predicts better CVD outcomes.", "protein": "Serum Albumin", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation may affect albumin's interaction with glucose.", "mechanism": "Higher sACR is inversely associated with diabetes complications.", "protein": "Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "GGT is glycosylated; glycosylation affects enzyme activity.", "mechanism": "Elevated GGT is positively associated with NAFLD risk.", "protein": "Gamma-glutamyl transpeptidase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALP is N-glycosylated; glycosylation modulates activity and clearance.", "mechanism": "Higher ALP levels are associated with increased NAFLD risk.", "protein": "Alkaline Phosphatase (ALP)", "relationship_type": "biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Higher HDL-c levels are associated with lower NAFLD risk and modify the protective effect of sACR.", "protein": "High-density lipoprotein cholesterol (HDL-c)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12382065" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "N-glycosylation modulates cytokine stability and secretion", "mechanism": "Promotes vascular inflammation and degradation of aortic wall", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "N-glycosylation affects receptor binding and activity", "mechanism": "Induces inflammatory cell infiltration and protease activation in aortic tissue", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "O-glycosylation influences hormone stability", "mechanism": "Elevated in MetS, stimulates vascular inflammation and macrophage migration", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "N-glycosylation modulates secretion", "mechanism": "Promotes local inflammation and aortic wall remodeling", "protein": "Resistin", "protein_enriched": { "function": "Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cel", "gene_name": "RETN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9HD89" }, "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "N-glycosylation affects cytokine activity", "mechanism": "Drives inflammatory response and protease production in aortic tissue", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "N-glycosylation modulates cytokine secretion", "mechanism": "Contributes to chronic inflammation in MetS and AA development", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "high", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "Apolipoproteins in HDL are glycosylated, affecting anti-inflammatory properties", "mechanism": "Genetically higher HDL-C reduces AA risk", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "protective", "source_pmcid": "PMC12382083" }, { "confidence": "high", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "Apolipoprotein glycosylation modulates lipoprotein function", "mechanism": "Elevated TG increases AA risk via vascular inflammation", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "causal", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "Non-enzymatic glycation of proteins alters extracellular matrix properties", "mechanism": "AGEs increase collagen cross-linking, reducing aortic wall stress and AA risk", "protein": "Advanced glycation end-products (AGEs)", "relationship_type": "protective", "source_pmcid": "PMC12382083" }, { "confidence": "medium", "disease": "Aortic aneurysm (AA)", "glycan_involvement": "O-glycosylation affects collagen fibril formation and stability", "mechanism": "Increased collagen synthesis thickens vessel wall, lowering AA risk in hyperglycemia/T2DM", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12382083" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "Glycosylation may affect stability and localization at tight junctions.", "mechanism": "Loss/degradation of CLDN5 correlates with BBB breakdown and vasogenic oedema in stroke.", "protein": "Claudin-5 (CLDN5)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "Glycosylation may regulate membrane trafficking and function.", "mechanism": "Phosphorylation and removal of OCLN from membrane triggers TJ remodelling and BBB leakage.", "protein": "Occludin (OCLN)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "medium", "disease": "Ischaemic Stroke", "glycan_involvement": "Indirect; glycosylation may affect protein-protein interactions.", "mechanism": "Loss of ZO-1 is associated with increased paracellular permeability during stroke.", "protein": "Zonula Occludens-1 (ZO-1/TJP1)", "relationship_type": "biomarker", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "N-glycosylation modulates adhesive function and stability.", "mechanism": "CDH5 regulates TJ protein expression; its phosphorylation/internalization increases permeability.", "protein": "Vascular Endothelial Cadherin (CDH5)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "Glycosylation may affect caveolae formation and trafficking.", "mechanism": "Upregulation of CAV1 increases caveolae-mediated transcytosis, contributing to early BBB leakage.", "protein": "Caveolin-1 (CAV1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12382098" }, { "confidence": "medium", "disease": "Ischaemic Stroke", "glycan_involvement": "Potential N-glycosylation affects membrane localization.", "mechanism": "MFSD2A suppresses caveolae formation, maintaining BBB integrity; its loss increases transcytosis.", "protein": "MFSD2A", "protein_enriched": { "function": "Probable serine protease which may play a role in cellular senescence. Overexpression inhibits cell growth and induce G1 cell cycle arrest", "gene_name": "TMPRSS11A", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q6ZMR5" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "Glycosylation may regulate channel gating and localization.", "mechanism": "AQP4 mediates water influx in cytotoxic oedema; inhibition reduces swelling.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Ischaemic Stroke", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "MMP-9 degrades TJ proteins, promoting BBB breakdown and vasogenic oedema.", "protein": "Matrix Metalloproteinase-9 (MMP-9)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "medium", "disease": "Ischaemic Stroke", "glycan_involvement": "N-glycosylation critical for receptor function.", "mechanism": "TFRC-mediated transcytosis is upregulated in BBB dysfunction, relevant for drug delivery.", "protein": "Transferrin Receptor (TFRC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "N-glycosylation modulates transporter activity.", "mechanism": "ABCB1 effluxes amyloid-\u03b2, protecting BBB; dysfunction linked to AD pathology.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12382098" }, { "confidence": "high", "disease": "Coronary Heart Disease", "glycan_involvement": "Non-enzymatic glycation alters albumin structure and function, reflecting glyco-oxidative stress.", "mechanism": "Glycation and oxidative modification patterns differ in diabetes; glycated albumin predominates in T2D, S-thiolated albumin in non-diabetics.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycation of albumin is a direct result of excess glucose; impacts protein function and vascular risk.", "mechanism": "Glycated albumin levels are elevated in T2D, indicating chronic hyperglycemia and glyco-oxidative stress.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin beta chain by glucose.", "mechanism": "HbA1c reflects average blood glucose over prior months; used for diagnosis and monitoring.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "medium", "disease": "Coronary Heart Disease", "glycan_involvement": "Glycation reflects chronic hyperglycemia, contributing to vascular damage.", "mechanism": "Higher HbA1c is associated with increased risk of coronary events in T2D.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "medium", "disease": "Cerebrovascular Disease", "glycan_involvement": "Glycation of albumin may impair renal filtration and vascular integrity.", "mechanism": "Microalbuminuria indicates endothelial dysfunction and predicts vascular complications.", "protein": "Microalbuminuria (Albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "medium", "disease": "Cerebrovascular Disease", "glycan_involvement": "Glycation alters albumin\u2019s antioxidant properties, promoting vascular damage.", "mechanism": "Glycated albumin is linked to increased risk of cerebrovascular events in T2D.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "low", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Glycation impairs albumin\u2019s function, exacerbating cardiac tissue damage.", "mechanism": "Glycated albumin may contribute to myocardial dysfunction via oxidative stress.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "low", "disease": "Heart Failure", "glycan_involvement": "Glycation affects albumin\u2019s vascular and cardiac protective roles.", "mechanism": "Elevated glycated albumin may reflect increased risk of heart failure in T2D.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "low", "disease": "Atrial Fibrillation", "glycan_involvement": "Glycation may alter electrophysiological properties indirectly.", "mechanism": "Glycated albumin may be associated with arrhythmogenic risk in diabetes.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "medium", "disease": "Carotid Artery Stenosis", "glycan_involvement": "Glycation promotes endothelial dysfunction and plaque formation.", "mechanism": "Glycated albumin is linked to atherosclerotic changes in carotid arteries.", "protein": "Human Serum Albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12382123" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "CEA is a heavily glycosylated cell adhesion molecule; abnormal glycosylation increases in cancer.", "mechanism": "Serum CEA decrease after immunochemotherapy predicts tumor response.", "protein": "CEA", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "CA19-9 is a sialylated Lewis antigen; altered glycosylation reflects tumor burden.", "mechanism": "Decrease in CA19-9 after treatment correlates with response to immunochemotherapy.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CA72-4 is a mucin-type glycoprotein; aberrant O-glycosylation in cancer.", "mechanism": "Decrease in CA72-4 after treatment is associated with better response.", "protein": "CA72-4", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CA242 is a sialylated carbohydrate antigen; glycosylation changes in malignancy.", "mechanism": "Dynamic changes in CA242 levels reflect tumor response or progression.", "protein": "CA242", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "AFP is N-glycosylated; glycoforms may affect detection and function.", "mechanism": "Significant decrease in AFP after immunochemotherapy in responders.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CA125 is a highly O-glycosylated mucin; altered glycosylation in cancer.", "mechanism": "Decrease in CA125 after treatment is associated with response.", "protein": "CA125/MUC16", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "IL-10 is N-glycosylated; glycosylation may affect secretion/stability.", "mechanism": "Elevated post-treatment serum IL-10 predicts better response to immunochemotherapy.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Albumin is N-glycosylated; glycosylation status may affect half-life.", "mechanism": "Higher pre-treatment albumin predicts better response and prognosis.", "protein": "Serum albumin", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "IFN-\u03b3 is glycosylated; glycosylation may modulate activity.", "mechanism": "Higher post-treatment IFN-\u03b3 correlates with response to immunochemotherapy.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation may influence receptor binding.", "mechanism": "Higher post-treatment TNF-\u03b1 associated with response.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382200" }, { "confidence": "high", "disease": "Alcohol-Related Liver Disease (ALD)", "glycan_involvement": "FASN is glycosylated for stability and activity.", "mechanism": "Naringenin decreases FASN activity, reducing hepatic lipogenesis and steatosis.", "protein": "FASN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "high", "disease": "Alcohol-Related Liver Disease (ALD)", "glycan_involvement": "G6PD glycosylation affects enzyme function.", "mechanism": "Naringenin reduces G6PD activity, limiting NADPH supply for fatty acid synthesis.", "protein": "G6PD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "medium", "disease": "Hepatitis B Virus Infection", "glycan_involvement": "SREBP1c glycosylation regulates nuclear translocation.", "mechanism": "Naringenin suppresses SREBP1c transcriptional activity, inhibiting HBV X protein-induced steatosis.", "protein": "SREBP1c", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "medium", "disease": "Hepatitis B Virus Infection", "glycan_involvement": "LXR\u03b1 glycosylation modulates receptor activity.", "mechanism": "Naringenin inhibits LXR\u03b1, reducing lipid accumulation in HBV-infected hepatocytes.", "protein": "LXR\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "medium", "disease": "Hepatitis B Virus Infection", "glycan_involvement": "PPAR\u03b3 glycosylation affects ligand binding.", "mechanism": "Naringenin suppresses PPAR\u03b3, limiting HBV X protein-driven hepatic steatosis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "high", "disease": "Hepatitis C Virus Infection", "glycan_involvement": "LDL glycoprotein components are essential for viral particle assembly.", "mechanism": "Naringenin blocks LDL assembly, inhibiting HCV particle formation and secretion.", "protein": "LDL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "NLRP3 glycosylation regulates inflammasome assembly.", "mechanism": "Naringenin inhibits NLRP3 inflammasome activation, reducing hepatic inflammation and steatosis.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "Naringenin reduces IL-1\u03b2 expression, attenuating liver inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "EZH2 glycosylation influences chromatin remodeling.", "mechanism": "EZH2 overexpression drives HCC progression; epigenetic modulation by flavonoids may suppress EZH2.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "medium", "disease": "Liver Steatosis", "glycan_involvement": "HDAC3 glycosylation affects nuclear localization and function.", "mechanism": "HDAC3 depletion promotes steatosis; flavonoids may modulate HDAC3 activity to restore metabolic homeostasis.", "protein": "HDAC3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382628" }, { "confidence": "high", "disease": "Apoptosis-mediated cell death", "glycan_involvement": "FAS is a glycoprotein; glycosylation modulates receptor clustering and apoptotic signaling.", "mechanism": "FAS upregulation triggers hepatocyte apoptosis under heat stress.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "high", "disease": "Apoptosis-mediated cell death", "glycan_involvement": "Caspase 3 is glycosylated; glycosylation may affect stability and activity.", "mechanism": "Caspase 3 activation executes apoptosis in liver cells during heat stress.", "protein": "Caspase 3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "TNF-\u03b1 upregulation indicates inflammatory response in liver and intestine under heat stress.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382668" }, { "confidence": "high", "disease": "Immune dysregulation", "glycan_involvement": "TLR2 is N-glycosylated; glycosylation is essential for ligand recognition and signaling.", "mechanism": "TLR2 upregulation activates innate immune response and inflammation in liver.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "high", "disease": "Endotoxin-mediated liver damage", "glycan_involvement": "Aeromonas LPS and O-antigen glycoproteins trigger host immune response.", "mechanism": "Aeromonas overgrowth increases endotoxin production, promoting liver injury.", "protein": "Aeromonas", "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Surface glycans may modulate host-microbe interactions and immune signaling.", "mechanism": "Anaerorhabdus_furcosa_group abundance correlates with increased hepatic immune/apoptosis gene expression.", "protein": "Anaerorhabdus_furcosa_group", "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Microbiota dysbiosis", "glycan_involvement": "Surface glycoproteins mediate colonization and host immune modulation.", "mechanism": "Cetobacterium decline under heat stress reduces butyrate production, weakening anti-inflammatory protection.", "protein": "Cetobacterium", "relationship_type": "protective", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "STAT1a glycosylation may regulate nuclear translocation and transcriptional activity.", "mechanism": "STAT1a upregulation marks activation of antiviral and immune pathways under heat stress.", "protein": "STAT1a", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "NOD1 is glycosylated; glycosylation affects receptor function.", "mechanism": "NOD1 upregulation activates inflammatory signaling in response to heat stress and microbial changes.", "protein": "NOD1", "protein_enriched": { "function": "Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses (PubMed:11058605, PubMed:1", "gene_name": "NOD1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y239" }, "relationship_type": "causal", "source_pmcid": "PMC12382668" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "IRF9 glycosylation may modulate protein stability and DNA binding.", "mechanism": "IRF9 upregulation indicates interferon pathway activation during heat stress.", "protein": "IRF9", "protein_enriched": { "function": "Transcription factor that plays an essential role in anti-viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kin", "gene_name": "IRF9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q00978" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382668" }, { "confidence": "high", "disease": "Testicular fibrosis", "glycan_involvement": "PDGFR\u03b1 is a glycoprotein; glycosylation is essential for receptor function and signaling.", "mechanism": "Upregulated in fibrotic testes after LDR radiation; mediates fibroblast activation and ECM deposition.", "protein": "PDGFR\u03b1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Testicular fibrosis", "glycan_involvement": "TGF-\u03b2 is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Promotes myofibroblast activation and collagen synthesis in response to apoptosis and ROS.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12382720" }, { "confidence": "high", "disease": "Testicular fibrosis", "glycan_involvement": "Collagen I is glycosylated; glycosylation modulates fibril formation and stability.", "mechanism": "Major ECM component; increased deposition marks fibrosis progression.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Testicular fibrosis", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation influences secretion and receptor interaction.", "mechanism": "Pro-inflammatory cytokine; upregulated in fibrosis models, promotes inflammation and ECM remodeling.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Male infertility", "glycan_involvement": "Glycosylation required for PDGFR\u03b1 signaling in fibrotic response.", "mechanism": "Fibrosis mediated by PDGFR\u03b1 disrupts testicular architecture, impairing spermatogenesis.", "protein": "PDGFR\u03b1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Male infertility", "glycan_involvement": "Glycosylation modulates TGF-\u03b2 bioactivity.", "mechanism": "Induces fibrosis and germ cell loss, leading to infertility.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Male infertility", "glycan_involvement": "Glycosylation affects collagen assembly and tissue structure.", "mechanism": "Excess collagen disrupts seminiferous tubule function.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Testicular apoptosis", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Upregulated in response to cell death, indicating active fibrotic remodeling.", "protein": "PDGFR\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Testicular apoptosis", "glycan_involvement": "Glycosylation affects TGF-\u03b2 signaling.", "mechanism": "Released during apoptosis, drives fibrosis.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12382720" }, { "confidence": "medium", "disease": "Testicular apoptosis", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "Promotes apoptosis and inflammation in testicular tissue.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382720" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is heavily glycosylated; glycosylation affects its processing and aggregation.", "mechanism": "Genistein inhibits APP secretion and \u03b2-site APP-cleaving enzyme 1, reducing amyloid plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau O-glycosylation modulates aggregation and phosphorylation.", "mechanism": "Genistein reduces tau phosphorylation via Nrf2/HO-1/PI3K pathway, limiting neurofibrillary tangle formation.", "protein": "Tau protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "\u03b1S glycosylation influences aggregation and toxicity.", "mechanism": "Lewy bodies containing \u03b1S are hallmark of PD; genistein enhances antioxidant capacity but does not reduce \u03b1S expression.", "protein": "Alpha-synuclein (\u03b1S)", "relationship_type": "biomarker", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SOD glycosylation affects stability and activity.", "mechanism": "Genistein upregulates SOD via Nrf2 pathway, protecting neurons from oxidative damage.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "GPx glycosylation modulates enzyme activity.", "mechanism": "Genistein increases GPx expression, reducing oxidative stress in pancreatic cells.", "protein": "Glutathione peroxidase (GPx)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles", "gene_name": "Gsta4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24472" }, "relationship_type": "protective", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CAT glycosylation influences enzyme stability.", "mechanism": "Genistein upregulates CAT, decreasing ROS and vascular inflammation.", "protein": "Catalase (CAT)", "protein_enriched": { "function": "", "gene_name": "Prss1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00762" }, "relationship_type": "protective", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "HO-1 glycosylation affects cellular localization and function.", "mechanism": "Genistein activates HO-1 via Nrf2, repairing acetaldehyde-induced liver damage and inhibiting hepatocellular carcinoma.", "protein": "Hemoxygenase 1 (HO-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "INSR N-glycosylation is essential for receptor folding and function.", "mechanism": "Genistein improves insulin signaling and sensitivity by modulating INSR pathways.", "protein": "Insulin receptor (INSR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Bax glycosylation may affect apoptotic signaling.", "mechanism": "Genistein upregulates Bax, promoting apoptosis in cancer cells.", "protein": "Bcl-2-associated X protein (Bax)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Cyclin D1 O-glycosylation regulates cell cycle progression.", "mechanism": "Genistein downregulates Cyclin D1, arresting cell cycle and inhibiting tumor growth.", "protein": "Cyclin D1", "protein_enriched": { "function": "Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran", "gene_name": "CCND1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24385" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382804" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect PLIN2 stability and CMA targeting.", "mechanism": "PLIN2 accumulation on lipid droplets impairs lipophagy, promoting hepatic steatosis.", "protein": "PLIN2", "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may regulate PLIN3 recognition by HSPA8/HSC70.", "mechanism": "PLIN3 is a CMA substrate; impaired degradation leads to lipid droplet persistence and steatosis.", "protein": "PLIN3", "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation critical for LAMP2A stability and function.", "mechanism": "LAMP2A mediates CMA of PLIN2/PLIN3; reduced function impairs lipophagy and promotes steatosis.", "protein": "LAMP2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for lysosomal targeting and activity.", "mechanism": "Suppressed CTSD activity impairs lysosomal degradation of lipid droplets, worsening steatosis.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation affects lysosomal localization and function.", "mechanism": "Reduced CTSB expression/activity disrupts lipophagy and promotes lipid accumulation.", "protein": "Cathepsin B (CTSB)", "protein_enriched": { "function": "Thiol protease which is believed to participate in intracellular degradation and turnover of proteins (By similarity). Cleaves matrix extracellular phosphoglycoprotein MEPE (By similarity). Involved i", "gene_name": "Ctsb", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G14260UH", "G48584BU", "G57776ZU", "G64527OM", "G28622IK", "G41247ZX" ], "uniprot_id": "P10605" }, "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation required for lysosomal activity.", "mechanism": "CTSL suppression impairs autophagic flux, contributing to hepatic steatosis.", "protein": "Cathepsin L (CTSL)", "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Potential glycosylation modulates membrane association.", "mechanism": "ANXA2 upregulation blocks autophagic flux via AMPK/mTOR pathway, exacerbating inflammation.", "protein": "Annexin A2 (ANXA2)", "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "N-glycosylation essential for lysosomal targeting and function.", "mechanism": "Decreased LAL activity impairs lysosomal acidification and lipid degradation.", "protein": "Lysosomal Acid Lipase (LAL)", "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Accumulation of p62 indicates impaired autophagic flux in MASLD.", "protein": "p62/SQSTM1", "protein_enriched": { "function": "Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub", "gene_name": "SQSTM1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13501" }, "relationship_type": "biomarker", "source_pmcid": "PMC12382931" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation may regulate inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation drives sterile inflammation in response to lipotoxicity.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12382931" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "O-glycosylation of flavonoids modulates solubility and bioactivity", "mechanism": "Antioxidant activity reduces ROS and inflammation", "protein": "Flavonoid glycosides", "relationship_type": "protective", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation affects antioxidant capacity and cellular uptake", "mechanism": "Reduces inflammatory processes and protects cells during inflammatory responses", "protein": "Flavonoid glycosides", "relationship_type": "protective", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "No direct glycosylation involvement mentioned", "mechanism": "Flavonoids activate glutathione peroxidase, reducing oxidative stress", "protein": "Glutathione peroxidase", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such ", "gene_name": "GPX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07203" }, "relationship_type": "protective", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement mentioned", "mechanism": "Flavonoids activate superoxide dismutase, lowering ROS and DNA damage", "protein": "Superoxide dismutase", "relationship_type": "protective", "source_pmcid": "PMC12382938" }, { "confidence": "high", "disease": "Stargardt disease", "glycan_involvement": "Cyclodextrin removes oxidized glycan-modified metabolites", "mechanism": "Accumulation of toxic bisretinoids generates ROS, leading to retinal damage", "protein": "Bisretinoid-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12382938" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Cyclodextrin removes oxidized glycan-modified cholesterol from plaques", "mechanism": "Accumulation of oxidized cholesterol promotes plaque formation", "protein": "7-ketocholesterol-modified proteins", "relationship_type": "causal", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement mentioned", "mechanism": "Luteolin suppresses XIAP, promoting apoptosis in cancer cells", "protein": "XIAP", "protein_enriched": { "function": "Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as", "gene_name": "XIAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P98170" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "No direct glycosylation involvement mentioned", "mechanism": "Luteolin inhibits NF-\u03baB, reducing cell survival and proliferation", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382938" }, { "confidence": "high", "disease": "Inflammatory pain", "glycan_involvement": "Cyclodextrin complexation enhances glycoprotein stability and delivery", "mechanism": "Cyclodextrin\u2013anthocyanin complexes exert anti-inflammatory and analgesic effects", "protein": "Cyclodextrin-modified glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382938" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates bioactivity and cellular interactions", "mechanism": "Antioxidant and anti-inflammatory effects reduce chronic inflammation", "protein": "Flavonoid glycosides", "relationship_type": "protective", "source_pmcid": "PMC12382938" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation modulates GPVI surface expression and ligand binding.", "mechanism": "GPVI-mediated platelet activation increases mitochondrial ROS, sensitizing mPTP opening and promoting thrombosis.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC12382986" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation required for integrin maturation and function.", "mechanism": "Integrin activation triggers platelet aggregation and is amplified by mPTP-dependent ROS signaling.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12382986" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "No direct glycosylation; effect is via regulation of glycoprotein-mediated signaling.", "mechanism": "CypD regulates mPTP opening; inhibition protects platelets from mitochondrial dysfunction and hyperactivity in diabetes.", "protein": "Cyclophilin D (CypD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382986" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Potential N-glycosylation affects channel gating.", "mechanism": "VDAC modulates mitochondrial permeability; altered function correlates with platelet exhaustion and DIC.", "protein": "Voltage-dependent anion channel (VDAC)", "relationship_type": "biomarker", "source_pmcid": "PMC12382986" }, { "confidence": "medium", "disease": "Acute Coronary Syndromes", "glycan_involvement": "Glycosylation may influence ligand binding and mitochondrial localization.", "mechanism": "TSPO ligands reduce mPTP opening and infarct size in preclinical models.", "protein": "Translocator protein (TSPO)", "protein_enriched": { "function": "Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipi", "gene_name": "TSPO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P30536" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382986" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation of subunits may affect complex stability.", "mechanism": "Dysfunctional ATP synthase may form mPTP, contributing to platelet hyperreactivity and vascular occlusion.", "protein": "F1F0-ATP synthase", "protein_enriched": { "function": "Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane whic", "gene_name": "ATP5F1B", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06576" }, "relationship_type": "causal", "source_pmcid": "PMC12382986" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation required for channel trafficking.", "mechanism": "Orai1-mediated SOCE drives mitochondrial calcium overload and mPTP opening; inhibition reduces platelet activation.", "protein": "Orai1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382986" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation modulates ER localization and function.", "mechanism": "STIM1 regulates SOCE; its inhibition prevents mPTP-mediated platelet dysfunction in inflammatory states.", "protein": "STIM1", "protein_enriched": { "function": "Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC)", "gene_name": "STIM1", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO", "G02815KT", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G46503DX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G80920RR" ], "uniprot_id": "Q13586" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382986" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "O-glycosylation may regulate mitochondrial binding.", "mechanism": "Hexokinase II modulates mPTP opening via metabolic control; targeting it may reduce platelet-mediated tumor progression.", "protein": "Hexokinase II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12382986" }, { "confidence": "medium", "disease": "Neurodegenerative Diseases", "glycan_involvement": "N-glycosylation affects GPVI stability and function.", "mechanism": "Altered GPVI signaling and platelet mitochondrial dysfunction may serve as biomarkers for systemic oxidative stress in neurodegeneration.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "biomarker", "source_pmcid": "PMC12382986" }, { "confidence": "high", "disease": "Stress-induced fitness loss", "glycan_involvement": "Glycosylation stabilizes HSP structure and function under stress.", "mechanism": "HSPs are upregulated in response to thermal stress, preventing cell damage and improving survival.", "protein": "Heat Shock Proteins (HSPs)", "relationship_type": "protective", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Bacterial infection", "glycan_involvement": "Glycosylation enhances antimicrobial activity.", "mechanism": "Increased antibacterial activity in hemolymph after heat shock improves resistance to bacterial pathogens.", "protein": "Hemolymph antibacterial glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Stress-induced fitness loss", "glycan_involvement": "Glycosylation modulates receptor binding and signaling.", "mechanism": "Octopamine levels rise after mechanical stress, indicating stress response.", "protein": "Octopamine-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Contaminant toxicity", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "Catalase activity increases in response to chemical stress, reducing oxidative damage.", "protein": "Catalase (glycosylated form)", "relationship_type": "protective", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Protein biosynthesis inhibition", "glycan_involvement": "Glycosylation is required for proper RNA binding and function.", "mechanism": "Anti-tumoral drugs inhibit RNA-binding glycoproteins, blocking nucleic acid and protein synthesis.", "protein": "RNA-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Protein biosynthesis inhibition", "glycan_involvement": "Glycosylation regulates substrate specificity.", "mechanism": "Drugs interfere with nucleoside incorporation, inhibiting protein synthesis.", "protein": "Nucleoside-incorporating glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Developmental delay", "glycan_involvement": "Glycosylation is essential for silk protein assembly.", "mechanism": "Antibiotic exposure alters silk glycoprotein synthesis, affecting cocoon development.", "protein": "Silkworm silk glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12383037" }, { "confidence": "medium", "disease": "Immune suppression", "glycan_involvement": "Glycosylation is critical for immune recognition and signaling.", "mechanism": "Stress and contaminants suppress immune glycoprotein expression, increasing disease susceptibility.", "protein": "Immune-related glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC12383037" }, { "confidence": "low", "disease": "Antibiotic resistance", "glycan_involvement": "Glycosylation affects substrate binding and degradation efficiency.", "mechanism": "Glycoproteins degrade antibiotics, contributing to resistance development.", "protein": "Antibiotic-degrading glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12383037" }, { "confidence": "low", "disease": "Zoonosis risk", "glycan_involvement": "Glycan structures determine pathogen binding specificity.", "mechanism": "Altered glycoprotein-mediated pathogen recognition increases zoonosis risk in high-density farming.", "protein": "Pathogen recognition glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12383037" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "ALP levels indicate hepatic function; unchanged by AuNPs, suggesting no liver toxicity.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "AST is glycosylated; glycosylation modulates activity.", "mechanism": "AST levels indicate hepatic function; unchanged by AuNPs, suggesting no liver toxicity.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "ALT is glycosylated; glycosylation affects secretion.", "mechanism": "ALT elevation at low AuNPs dose suggests mild hepatocellular stress.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "LDH glycosylation influences stability.", "mechanism": "LDH elevation at high AuNPs dose indicates cellular membrane damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Glycosylation regulates transporter localization.", "mechanism": "Urea levels unchanged by AuNPs, indicating minimal nephrotoxicity.", "protein": "Urea transporter", "protein_enriched": { "function": "Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient (PubMed:8812490). Unlike classica", "gene_name": "AQP6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q13520" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Creatinine levels unchanged by AuNPs, indicating minimal nephrotoxicity.", "protein": "Creatinine transporter", "protein_enriched": { "function": "Functions as a sodium-dependent neutral amino acid transporter. Exhibits preference for the branched-chain amino acids, particularly leucine, valine and isoleucine and methionine. Can also transport l", "gene_name": "SLC6A15", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G80920RR", "G41247ZX", "G49108TO" ], "uniprot_id": "Q9H2J7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation maintains ALP activity under stress.", "mechanism": "Stable ALP levels suggest protection against oxidative damage by AuNPs.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "protective", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation modulates LDH release.", "mechanism": "LDH elevation at high AuNPs dose reflects oxidative membrane damage.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Antimicrobial resistance (AMR)", "glycan_involvement": "Glycosylation supports ALP stability during infection.", "mechanism": "Stable ALP levels with AuNPs suggest reduced tissue damage during antimicrobial therapy.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "protective", "source_pmcid": "PMC12383043" }, { "confidence": "medium", "disease": "Bacterial infection (S. aureus, S. pneumoniae, E. coli, P. aeruginosa)", "glycan_involvement": "Glycosylation affects LDH secretion in response to infection.", "mechanism": "LDH release may indicate cell damage during infection or antimicrobial action.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383043" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HAMP1 is a glycosylated peptide hormone; glycosylation affects stability and secretion.", "mechanism": "HAMP1 expression correlates with MASLD severity and response to saponin therapy; reduction after treatment indicates improvement.", "protein": "HAMP1 (Hepcidin)", "relationship_type": "biomarker", "source_pmcid": "PMC12383080" }, { "confidence": "high", "disease": "Hepatic iron overload", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "Upregulation of HAMP1 reduces iron absorption; dysregulation leads to iron accumulation and oxidative stress.", "protein": "HAMP1 (Hepcidin)", "relationship_type": "causal", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "FN1 is heavily glycosylated; glycosylation modulates ECM interactions.", "mechanism": "FN1 expression increases with fibrosis; saponin treatment trends toward reduction.", "protein": "Fibronectin 1 (FN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 upregulated in MASLD; saponin therapy reduces IL-1\u03b2 levels.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "Glycosylation modulates chemokine activity and receptor binding.", "mechanism": "MCP-1 elevated in MASLD; saponin treatment decreases MCP-1, indicating reduced inflammation.", "protein": "MCP-1 (CCL2)", "relationship_type": "biomarker", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "IL6R is N-glycosylated; glycosylation affects receptor function.", "mechanism": "IL6R involved in IL6\u2013JAK\u2013STAT3 axis; saponin responders show decreased IL6R expression.", "protein": "IL6R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "Not glycosylated.", "mechanism": "STAT3 mediates inflammation and fibrosis; saponin treatment suppresses STAT3 signaling.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "Oxidative stress-induced liver injury", "glycan_involvement": "SOD1 glycosylation may affect stability.", "mechanism": "Saponin treatment upregulates SOD1, enhancing antioxidant defense.", "protein": "SOD1", "relationship_type": "protective", "source_pmcid": "PMC12383080" }, { "confidence": "medium", "disease": "Oxidative stress-induced liver injury", "glycan_involvement": "GPX1 glycosylation influences activity.", "mechanism": "GPX1 upregulated by saponins, reducing ROS and oxidative damage.", "protein": "GPX1", "relationship_type": "protective", "source_pmcid": "PMC12383080" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Elevated HAMP1 promotes iron retention and ROS, contributing to fibrosis; saponin-induced reduction mitigates fibrosis.", "protein": "HAMP1 (Hepcidin)", "relationship_type": "causal", "source_pmcid": "PMC12383080" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "CFTR is glycosylated; glycosylation affects its folding, trafficking, and function.", "mechanism": "CFTR mutation leads to defective chloride transport and altered glycoprotein function, contributing to oxidative stress and epithelial dysfunction.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC12383091" }, { "confidence": "high", "disease": "Acute Lung Injury", "glycan_involvement": "SP-A is heavily glycosylated, which is essential for its immune-modulatory and surfactant properties.", "mechanism": "SP-A modulates surfactant function and immune response; dysfunction contributes to impaired surfactant and inflammation.", "protein": "Surfactant Protein A (SP-A)", "relationship_type": "protective", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia", "glycan_involvement": "SP-B glycosylation is critical for surfactant function.", "mechanism": "SP-B maintains surfactant stability; dysfunction leads to impaired lung compliance and chronic injury.", "protein": "Surfactant Protein B (SP-B)", "relationship_type": "protective", "source_pmcid": "PMC12383091" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "O-glycosylation of mucins determines mucus properties.", "mechanism": "Mucins form mucus barrier; altered glycosylation affects mucus viscosity and barrier function, contributing to airway obstruction.", "protein": "Mucins", "relationship_type": "biomarker", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation modulates aggregation propensity.", "mechanism": "Amyloid-\u03b2 aggregation leads to tissue dysfunction; \u03b2-CDs reduce aggregation.", "protein": "Amyloid-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "Lung Cancer", "glycan_involvement": "Glycosylation affects receptor localization and ligand binding.", "mechanism": "Overexpressed in cancer cells; \u03b2-CD conjugates used for targeted imaging.", "protein": "Prostaglandin E2 receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation influences stability and aggregation.", "mechanism": "Misfolded transthyretin forms amyloid deposits; \u03b2-CDs reduce aggregation.", "protein": "Transthyretin", "relationship_type": "causal", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "N-glycosylation modulates prion protein folding and aggregation.", "mechanism": "Prion protein misfolding leads to aggregation; \u03b2-CDs inhibit aggregation.", "protein": "Prion Protein", "relationship_type": "causal", "source_pmcid": "PMC12383091" }, { "confidence": "high", "disease": "Biofilm-associated infection in CF", "glycan_involvement": "O-glycosylation provides cysteine-rich domains for interaction.", "mechanism": "Thiolated \u03b2-CDs form disulfide bonds with mucin glycoproteins, enhancing drug mucoadhesion and penetration.", "protein": "Mucins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383091" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for SP-A's antiviral activity.", "mechanism": "SP-A contributes to antiviral barrier; \u03b2-CDs enhance surfactant function and reduce viral attachment.", "protein": "Surfactant Protein A (SP-A)", "relationship_type": "protective", "source_pmcid": "PMC12383091" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Glycosylation essential for IgA stability and function.", "mechanism": "AFB1 reduces IgA levels, indicating impaired humoral immunity; DSPS restores IgA.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC12383227" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Glycosylation modulates IgG effector functions.", "mechanism": "AFB1 suppresses IgG synthesis; DSPS reverses this effect.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383227" }, { "confidence": "high", "disease": "Immune dysfunction", "glycan_involvement": "Glycosylation required for IgM multimerization and activity.", "mechanism": "AFB1 decreases IgM levels; DSPS increases IgM, improving immune response.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "Glycosylation affects IFN-\u03b3 secretion and stability.", "mechanism": "AFB1 lowers IFN-\u03b3, impairing cellular immunity; DSPS restores IFN-\u03b3.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "Glycosylation influences IL-4 receptor binding.", "mechanism": "AFB1 increases IL-4, skewing immune response; DSPS normalizes IL-4.", "protein": "IL-4", "relationship_type": "biomarker", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Hepatocyte apoptosis", "glycan_involvement": "Glycosylation may affect cyt.c mitochondrial localization.", "mechanism": "AFB1-induced ROS triggers cyt.c release, activating apoptosis; DSPS inhibits cyt.c release.", "protein": "Cytochrome c", "protein_enriched": { "function": "Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers ", "gene_name": "CYCS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P99999" }, "relationship_type": "causal", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Hepatocyte apoptosis", "glycan_involvement": "Potential glycosylation modulates caspase activity.", "mechanism": "AFB1 activates caspase 9 via mitochondrial pathway; DSPS suppresses caspase 9 activation.", "protein": "Caspase 9", "relationship_type": "causal", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Hepatocyte apoptosis", "glycan_involvement": "Glycosylation may regulate caspase 3 activation.", "mechanism": "AFB1 increases caspase 3, leading to apoptosis; DSPS reduces caspase 3 levels.", "protein": "Caspase 3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Aflatoxin B1-induced liver damage", "glycan_involvement": "Glycosylation affects CYP1A1 stability and localization.", "mechanism": "AFB1 upregulates CYP1A1, increasing toxic metabolite formation; DSPS inhibits CYP1A1 expression.", "protein": "CYP1A1", "relationship_type": "causal", "source_pmcid": "PMC12383227" }, { "confidence": "medium", "disease": "Aflatoxin B1-induced liver damage", "glycan_involvement": "Glycosylation modulates CYP1A2 enzymatic activity.", "mechanism": "AFB1 induces CYP1A2, promoting hepatotoxicity; DSPS downregulates CYP1A2.", "protein": "CYP1A2", "protein_enriched": { "function": "", "gene_name": "10A19I.14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV2" }, "relationship_type": "causal", "source_pmcid": "PMC12383227" }, { "confidence": "high", "disease": "Dialysis-related Amyloidosis", "glycan_involvement": "Glycosylation affects protein stability and aggregation propensity.", "mechanism": "Accumulation due to inadequate clearance leads to amyloid deposits in dialysis patients.", "protein": "\u03b22-microglobulin", "relationship_type": "causal", "source_pmcid": "PMC12383325" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation modulates plasma half-life and renal filtration.", "mechanism": "Elevated levels indicate impaired renal clearance of middle-molecular-weight glycoproteins.", "protein": "\u03b11-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12383325" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Glycosylation influences binding affinity for toxins.", "mechanism": "Albumin binds protein-bound uremic toxins (PBUTs), limiting their removal by dialysis.", "protein": "albumin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383325" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation regulates cytokine secretion and stability.", "mechanism": "Elevated IL-6 in blood reflects systemic inflammation and poor clearance in renal failure.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383325" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects chemokine activity and clearance.", "mechanism": "High IL-8 levels indicate inflammatory response and impaired renal clearance.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383325" }, { "confidence": "high", "disease": "Hyperbilirubinemia", "glycan_involvement": "Glycosylation modulates bilirubin binding and transport.", "mechanism": "Albumin binds bilirubin; removal strategies target albumin-bilirubin complexes.", "protein": "albumin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383325" }, { "confidence": "high", "disease": "End-stage Renal Disease", "glycan_involvement": "Glycosylation impacts renal filtration and aggregation.", "mechanism": "Elevated \u03b22-microglobulin is a marker of poor renal clearance and risk for amyloidosis.", "protein": "\u03b22-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12383325" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation alters toxin binding and endothelial interactions.", "mechanism": "Albumin-bound toxins (e.g., indoxyl sulfate, p-cresyl sulfate) promote vascular dysfunction.", "protein": "albumin", "relationship_type": "causal", "source_pmcid": "PMC12383325" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects plasma stability and vascular deposition.", "mechanism": "High \u03b22-microglobulin levels correlate with increased cardiovascular risk in CKD.", "protein": "\u03b22-microglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC12383325" }, { "confidence": "high", "disease": "End-stage Renal Disease", "glycan_involvement": "Glycosylation modulates PBUT binding and removal efficiency.", "mechanism": "Albumin-bound PBUTs are poorly cleared, contributing to uremic toxicity.", "protein": "albumin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383325" }, { "confidence": "high", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "Fibronectin is heavily glycosylated; glycosylation modulates its ECM interactions.", "mechanism": "Oligo-fucoidan downregulates fibronectin, reducing ECM accumulation and fibrotic remodeling in leiomyoma.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "Vimentin glycosylation affects filament assembly and cell signaling.", "mechanism": "Oligo-fucoidan suppresses vimentin expression, inhibiting fibrotic cell phenotype.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "Glycosylation modulates \u03b1-SMA stability and function.", "mechanism": "Oligo-fucoidan downregulates \u03b1-SMA, reducing myofibroblast activation and fibrosis.", "protein": "Alpha-smooth muscle actin (\u03b1-SMA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "high", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "Collagen glycosylation is critical for fibril formation and tissue integrity.", "mechanism": "Oligo-fucoidan reduces COL1A1 expression, limiting ECM deposition and fibroid growth.", "protein": "Collagen 1A1 (COL1A1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "SMAD2 glycosylation may affect nuclear translocation and signaling.", "mechanism": "Oligo-fucoidan inhibits SMAD2 phosphorylation, blocking TGF-\u03b23-driven fibrotic signaling.", "protein": "SMAD2", "protein_enriched": { "function": "Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds ", "gene_name": "SMAD2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15796" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "ERK glycosylation can modulate kinase activity.", "mechanism": "Oligo-fucoidan inhibits ERK1/2 phosphorylation, reducing cell proliferation in leiomyoma.", "protein": "ERK1/2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "\u03b2-catenin glycosylation regulates cell adhesion and signaling.", "mechanism": "Oligo-fucoidan inhibits \u03b2-catenin nuclear translocation, suppressing Wnt signaling and fibroid growth.", "protein": "\u03b2-catenin", "protein_enriched": { "function": "Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)", "gene_name": "CTNNB1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G59924QI" ], "uniprot_id": "P35222" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383344" }, { "confidence": "high", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "TGF-\u03b23 is glycosylated, affecting receptor binding and signaling.", "mechanism": "TGF-\u03b23 signaling drives fibrotic remodeling in leiomyoma; oligo-fucoidan modulates this pathway.", "protein": "TGF-\u03b23", "protein_enriched": { "function": "Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active su", "gene_name": "TGFB3", "glycan_count": 10, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G62765YT", "G64527OM", "G70101JE", "G80920RR", "G84452RH", "G57321FI", "G02886BB", "G45395BF", "G47702MW" ], "uniprot_id": "P10600" }, "relationship_type": "causal", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "ER glycosylation influences receptor stability and hormone binding.", "mechanism": "Estrogen signaling via ER promotes leiomyoma growth; oligo-fucoidan may modulate estrogen pathways.", "protein": "Estradiol receptor (ER)", "relationship_type": "causal", "source_pmcid": "PMC12383344" }, { "confidence": "medium", "disease": "Uterine leiomyoma (fibroid)", "glycan_involvement": "CRP glycosylation is essential for its immune functions.", "mechanism": "HS-CRP used to monitor systemic inflammation in leiomyoma patients.", "protein": "High-sensitivity C-reactive protein (HS-CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12383344" }, { "confidence": "high", "disease": "COVID-19 severe outcome", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP levels increase with inflammation and correlate with disease severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "COVID-19 severe outcome", "glycan_involvement": "N-glycosylation modulates IL-6 receptor binding and signaling.", "mechanism": "IL-6 is elevated in severe cases and drives hyperinflammation; anti-IL-6 therapy is used.", "protein": "Interleukin-6", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "COVID-19 severe outcome", "glycan_involvement": "N-glycosylation influences fibrinogen clotting properties.", "mechanism": "Fibrinogen is increased in inflammation and linked to thrombosis risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "COVID-19 severe outcome", "glycan_involvement": "Glycosylation affects ferritin secretion and immune recognition.", "mechanism": "Ferritin is elevated in severe cases, reflecting hyperinflammation and iron dysregulation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "medium", "disease": "COVID-19 severe outcome", "glycan_involvement": "Glycosylation may affect LDH stability and clearance.", "mechanism": "LDH is increased in tissue damage and correlates with severity.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "COVID-19 severe outcome", "glycan_involvement": "Glycan fragments are part of D-dimer structure.", "mechanism": "D-dimer is elevated in coagulopathy and predicts poor outcome.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "medium", "disease": "COVID-19 severe outcome", "glycan_involvement": "N-glycosylation affects AST secretion and activity.", "mechanism": "AST is increased in liver injury and predicts severity, especially in females.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "medium", "disease": "COVID-19 severe outcome", "glycan_involvement": "N-glycosylation modulates GGT enzymatic activity.", "mechanism": "GGT is elevated in liver dysfunction and correlates with severity.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383355" }, { "confidence": "medium", "disease": "COVID-19 post-acute syndrome", "glycan_involvement": "Fc N-glycosylation regulates IgG effector functions and inflammation.", "mechanism": "IgG levels reflect adaptive immune response and are higher in males post-infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "N-glycosylation modulates IL-6 receptor interactions.", "mechanism": "Elevated IL-6 is linked to increased mortality; anti-IL-6 therapy reduces risk.", "protein": "Interleukin-6", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12383355" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No direct glycosylation reported for E6; host cell glycoproteins may be affected.", "mechanism": "E6 promotes degradation of p53, leading to uncontrolled cell growth.", "protein": "HPV E6", "protein_enriched": { "function": "Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates wi", "gene_name": "E6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03126" }, "relationship_type": "causal", "source_pmcid": "PMC12383472" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "No direct glycosylation reported for E7; host cell glycoproteins may be affected.", "mechanism": "E7 inactivates pRb, promoting cell cycle progression.", "protein": "HPV E7", "protein_enriched": { "function": "Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA rep", "gene_name": "E7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03129" }, "relationship_type": "causal", "source_pmcid": "PMC12383472" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "p53 is glycosylated; glycosylation may affect stability and function.", "mechanism": "Restoration of p53 activity induces apoptosis in cancer cells.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383472" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Bcl-2 glycosylation may regulate its anti-apoptotic function.", "mechanism": "Downregulation of Bcl-2 promotes apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383472" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Cyclin A is glycosylated; glycosylation may affect cell cycle regulation.", "mechanism": "Downregulation indicates cell cycle arrest and apoptosis.", "protein": "Cyclin A", "protein_enriched": { "function": "Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-d", "gene_name": "CCNA2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20248" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383472" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Cyclin B is glycosylated; glycosylation may affect cell cycle regulation.", "mechanism": "Downregulation indicates cell cycle arrest and apoptosis.", "protein": "Cyclin B", "relationship_type": "biomarker", "source_pmcid": "PMC12383472" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Platelet glycoproteins are highly glycosylated; glycosylation is essential for function.", "mechanism": "Resveratrol inhibits platelet aggregation, reducing inflammation.", "protein": "Platelet glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12383472" }, { "confidence": "low", "disease": "Cervical cancer", "glycan_involvement": "p21 glycosylation may affect its regulatory activity.", "mechanism": "Upregulation of p21 leads to cell cycle arrest.", "protein": "p21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383472" }, { "confidence": "low", "disease": "Cervical cancer", "glycan_involvement": "CDK1 glycosylation may modulate kinase activity.", "mechanism": "Downregulation indicates cell cycle arrest.", "protein": "CDK1", "protein_enriched": { "function": "Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (Pub", "gene_name": "CDK1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P06493" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383472" }, { "confidence": "low", "disease": "Cervical cancer", "glycan_involvement": "CDK2 glycosylation may modulate kinase activity.", "mechanism": "Downregulation indicates cell cycle arrest.", "protein": "CDK2", "protein_enriched": { "function": "Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMe", "gene_name": "CDK2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383472" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation required for membrane localization and function.", "mechanism": "CD36 mediates fatty acid uptake, supporting tumor growth and ROS regulation.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383476" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation critical for cell surface expression.", "mechanism": "GLUT1 overexpression correlates with increased glucose uptake, glycolysis, and poor prognosis.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383476" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation modulates secretion and receptor binding.", "mechanism": "VEGF drives angiogenesis, supporting tumor growth and metastasis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383476" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation affects ligand binding and receptor activation.", "mechanism": "EGFR signaling promotes proliferation and survival; targeted by inhibitors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation required for receptor stability and dimerization.", "mechanism": "HER2 overexpression drives oncogenic signaling; targeted by trastuzumab.", "protein": "HER2/ErbB2", "protein_enriched": { "function": "Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, althou", "gene_name": "ERBB2", "glycan_count": 29, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G52890YB", "G96577RX", "G43417UB", "G14972EH", "G16125XL", "G43223CG", "G45395BF", "G62765YT", "G64527OM", "G70101JE", "G80920RR", "G87661QW", "G05724UK", "G31852PQ", "G39188ZX", "G81315DD", "G00912UN", "G08290VR", "G08918WF", "G41071NU", "G44215PV", "G48414YA", "G65184UU", "G66163OV", "G83646BJ", "G95133RI", "G15169WU", "G09724ZC", "G46524LG" ], "uniprot_id": "P04626" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may affect secretion and function.", "mechanism": "FABP4 upregulation at metastatic sites enhances lipid transfer and tumor progression.", "protein": "FABP4", "protein_enriched": { "function": "Important in genetic recombination, DNA repair, and replication. Possesses pairing and strand-transfer activity. Interacts with dda and gene 32 proteins", "gene_name": "UVSX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06727" }, "relationship_type": "causal", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may regulate enzyme stability.", "mechanism": "LDHA overexpression promotes aerobic glycolysis and tumor growth.", "protein": "LDHA", "protein_enriched": { "function": "Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)", "gene_name": "LDHA", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS", "G41247ZX", "G43223CG", "G57776ZS", "G84225JN", "G92406TI" ], "uniprot_id": "P00338" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "MMP-9 facilitates invasion and metastasis by degrading ECM.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation modulates ligand binding.", "mechanism": "ICAM-1 mediates cell adhesion, contributing to metastasis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383476" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "FASN overexpression supports lipid biosynthesis and tumor growth.", "protein": "FASN", "relationship_type": "biomarker", "source_pmcid": "PMC12383476" }, { "confidence": "high", "disease": "HNSCC", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor stability.", "mechanism": "EGFR overexpression drives tumor proliferation and survival; targeted by monoclonal antibodies and ADCs.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "high", "disease": "HNSCC", "glycan_involvement": "N-glycosylation stabilizes PD-L1 on cell surface, affecting immune recognition.", "mechanism": "PD-L1 expression predicts response to checkpoint inhibitors; regulates immune evasion.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "medium", "disease": "HNSCC", "glycan_involvement": "N-glycosylation affects receptor dimerization and signaling.", "mechanism": "HER3 overexpression associated with poor prognosis and resistance to anti-EGFR therapy.", "protein": "HER3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "high", "disease": "HNSCC", "glycan_involvement": "Glycosylation influences TF procoagulant activity and cell surface expression.", "mechanism": "TF promotes tumor growth, angiogenesis, and metastasis; targeted by ADCs.", "protein": "Tissue Factor (TF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "high", "disease": "HNSCC", "glycan_involvement": "N-glycosylation required for cell adhesion and surface localization.", "mechanism": "Nectin-4 overexpression promotes tumorigenesis and angiogenesis; targeted by ADCs.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "medium", "disease": "HNSCC", "glycan_involvement": "Glycosylation modulates TROP-2 stability and signaling.", "mechanism": "TROP-2 overexpression drives cell proliferation and migration; targeted by ADCs.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "medium", "disease": "HNSCC", "glycan_involvement": "O-glycosylation in mucin domain affects ligand binding.", "mechanism": "TIM-3 inhibits T cell activation; blockade enhances anti-tumor immunity.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "medium", "disease": "HNSCC", "glycan_involvement": "N-glycosylation modulates receptor stability and immune interactions.", "mechanism": "LAG-3 overexpression correlates with poor prognosis and immune suppression.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "medium", "disease": "HNSCC", "glycan_involvement": "N-glycosylation required for receptor maturation and signaling.", "mechanism": "MET overexpression linked to poor prognosis and resistance to EGFR inhibitors.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. 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inhibitors show clinical activity.", "protein": "FGFR1-4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383497" }, { "confidence": "high", "disease": "Cancer Cachexia", "glycan_involvement": "GDF15 is a secreted glycoprotein; glycosylation required for stability and secretion.", "mechanism": "GDF15-GFRAL axis regulates appetite and muscle/adipose loss; antibody inhibition reverses cachexia.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation supports secretion and dimerization, enabling paracrine/autocrine signaling.", "mechanism": "Promotes EMT, metastasis, and chemoresistance via SMAD2/3 and PI3K/AKT/Nrf2 pathways.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "Glycosylation required for mature, circulating form.", "mechanism": "Autocrine GDF15-GFRAL axis drives tumor growth, metastasis, and immune evasion.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation affects secretion and ECM interaction.", "mechanism": "High GDF15 promotes invasion/metastasis via FAK-RhoA and EGR1; correlates with poor survival.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Glycosylation required for secretion and dimerization.", "mechanism": "Overexpression linked to aggressive phenotype, radio/chemoresistance, poor ICI response.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation supports functional secretion.", "mechanism": "Correlates with high grade, ER-negativity, HER2-positivity; promotes EMT, invasion, and therapy resistance.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Glycosylation required for circulating biomarker activity.", "mechanism": "Elevated GDF15 linked to advanced stage, poor survival, and cisplatin resistance.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Lung Cancer", "glycan_involvement": "Glycosylation supports secretion and stability.", "mechanism": "High serum GDF15 predicts poor outcome, reduced chemo efficacy, and immune evasion.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12383714" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Overexpression associated with BRAF mutation, poor prognosis, and ICI failure.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "medium", "disease": "Cancer Cachexia", "glycan_involvement": "ZAG is a glycoprotein; glycosylation essential for lipolytic activity.", "mechanism": "Upregulated in cachexia, correlates with adipose depletion and weight loss.", "protein": "ZAG", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383714" }, { "confidence": "high", "disease": "Stevens\u2013Johnson syndrome (SJS)", "glycan_involvement": "MHC class I glycoprotein; glycosylation required for antigen presentation.", "mechanism": "Presence of HLA-B*15:02 allele increases risk of SJS with carbamazepine/oxcarbazepine.", "protein": "HLA-B*15:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G04854VP", "G08918WF", "G10488MI", "G15664MX", "G20706XG", "G27058EU", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G62765YT", "G70101JE", "G72747WU", "G77669RF", "G80920RR", "G90659AW", "G92135MA", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Toxic epidermal necrolysis (TEN)", "glycan_involvement": "Glycosylation modulates peptide binding and immune recognition.", "mechanism": "HLA-B*15:02 allele strongly associated with TEN after carbamazepine/oxcarbazepine exposure.", "protein": "HLA-B*15:02", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-B", "glycan_count": 21, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G04854VP", "G08918WF", "G10488MI", "G15664MX", "G20706XG", "G27058EU", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G62765YT", "G70101JE", "G72747WU", "G77669RF", "G80920RR", "G90659AW", "G92135MA", "G95177YH", "G43417UB", "G49108TO" ], "uniprot_id": "P01889" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Drug reaction with eosinophilia and systemic symptoms (DRESS)", "glycan_involvement": "MHC class I glycoprotein; glycosylation affects immune response.", "mechanism": "HLA-A*31:01 allele increases risk of DRESS and other hypersensitivity reactions to carbamazepine.", "protein": "HLA-A*31:01", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "medium", "disease": "Neuropathic pain", "glycan_involvement": "N-glycosylation critical for membrane localization and drug transport.", "mechanism": "ABCB1 polymorphisms modulate CNS drug exposure and efficacy of TCAs and opioids.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383745" }, { "confidence": "medium", "disease": "Opioid-induced respiratory depression", "glycan_involvement": "Glycosylation influences receptor folding and ligand binding.", "mechanism": "OPRM1 A118G variant alters receptor function, affecting opioid dose requirements and risk.", "protein": "OPRM1 (\u03bc-opioid receptor)", "protein_enriched": { "function": "Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synt", "gene_name": "OPRM1", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P35372" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Opioid-induced respiratory depression", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "CYP2D6 ultrarapid metabolizers convert codeine/tramadol to active metabolites rapidly, increasing toxicity risk.", "protein": "CYP2D6", "protein_enriched": { "function": "", "gene_name": "10A19I.15", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9XHV1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Gastrointestinal bleeding", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "CYP2C9 poor metabolizers have increased NSAID exposure, raising GI bleeding risk.", "protein": "CYP2C9", "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Renal impairment", "glycan_involvement": "Glycosylation affects enzyme function.", "mechanism": "Reduced CYP2C9 function leads to NSAID accumulation and renal toxicity.", "protein": "CYP2C9", "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Cardiovascular events", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Poor CYP2C9 metabolizers have higher NSAID plasma levels, increasing cardiovascular risk.", "protein": "CYP2C9", "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "medium", "disease": "Antidepressant-induced QT prolongation", "glycan_involvement": "N-glycosylation required for transporter function.", "mechanism": "ABCB1 variants may alter CNS exposure to SSRIs/TCAs, influencing QT risk.", "protein": "ABCB1 (P-glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC12383745" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Promotes adipose inflammation and insulin resistance via NF-\u03baB pathway.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "IL-1\u03b2 is glycosylated, influencing its activity and secretion.", "mechanism": "Induces \u03b2-cell dysfunction and systemic inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12383914" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "IL-6 glycosylation modulates receptor binding.", "mechanism": "Elevated in HFD-induced obesity, linked to insulin resistance.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "IL-10 glycosylation affects anti-inflammatory function.", "mechanism": "Anti-inflammatory cytokine; reduced in obesity, restored by CGA.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Leptin is glycosylated; glycosylation affects receptor interaction.", "mechanism": "Elevated in obesity, indicating leptin resistance.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Adiponectin glycosylation critical for multimerization and function.", "mechanism": "Reduced in obesity; restoration improves insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12383914" }, { "confidence": "medium", "disease": "Adipose tissue dysfunction", "glycan_involvement": "Glycosylation modulates IFN-\u03b3 secretion and activity.", "mechanism": "Promotes Th1-mediated inflammation in adipose tissue.", "protein": "IFN-\u03b3", "relationship_type": "causal", "source_pmcid": "PMC12383914" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "TGF-\u03b2 glycosylation affects secretion and receptor binding.", "mechanism": "Promotes fibrosis and immune dysregulation in liver.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Activation modulated by upstream glycoprotein cytokines.", "mechanism": "Central mediator of inflammatory gene expression; activated in obesity.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12383914" }, { "confidence": "medium", "disease": "Adipose tissue dysfunction", "glycan_involvement": "Indirect; apoptosis signaling influenced by glycoprotein cytokines.", "mechanism": "Upregulated in HFD-induced apoptosis of adipocytes.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383914" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Altered glycosylation affects TREM2 stability and ligand binding.", "mechanism": "Disrupted glycoprotein-mediated microglial signaling impairs debris clearance and amplifies neuroinflammation.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates PSD-95 localization and stability at synapses.", "mechanism": "A\u03b2 oligomers induce calpain-mediated cleavage of PSD-95, disrupting synaptic glycoprotein scaffolding and plasticity.", "protein": "PSD-95", "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "N-glycosylation critical for LAMP2A channel assembly and substrate recognition.", "mechanism": "Impaired glycoprotein channel function blocks chaperone-mediated autophagy, leading to \u03b1-synuclein accumulation.", "protein": "LAMP2A", "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation affects GRP75 stability and organelle interaction.", "mechanism": "Loss of ER-mitochondria tethering via GRP75 impairs calcium signaling and energy metabolism.", "protein": "GRP75", "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates C1q recognition and effector function.", "mechanism": "Complement-mediated synaptic pruning via C1q\u2013CR3 axis leads to synaptic loss.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "Glycosylation required for SNAP29 trafficking and fusion competence.", "mechanism": "Defective glycoprotein SNARE complex impairs autophagosome\u2013lysosome fusion, causing proteostatic collapse.", "protein": "SNAP29", "protein_enriched": { "function": "SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans", "gene_name": "VAMP8", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q9BV40" }, "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Frontotemporal Dementia", "glycan_involvement": "N-glycosylation modulates STX17 membrane targeting.", "mechanism": "Impaired SNARE glycoprotein function blocks autophagic flux, leading to aggregate accumulation.", "protein": "STX17", "protein_enriched": { "function": "In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a r", "gene_name": "KRTAP4-7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYR0" }, "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Rab5 glycosylation affects endosomal sorting.", "mechanism": "Hyperactivation enlarges early endosomes, delaying glycoprotein receptor recycling and BDNF signaling.", "protein": "Rab5", "protein_enriched": { "function": "The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a", "gene_name": "RAB5A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20339" }, "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates Rab11 vesicle targeting.", "mechanism": "Impaired Rab11 function reduces recycling of synaptic glycoproteins, weakening LTP.", "protein": "Rab11", "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "medium", "disease": "Amyotrophic Lateral Sclerosis", "glycan_involvement": "Aberrant glycosylation may influence TDP-43 aggregation propensity.", "mechanism": "Cytoplasmic aggregation of glycoprotein TDP-43 disrupts RNA processing and nucleocytoplasmic transport.", "protein": "TDP-43", "relationship_type": "causal", "source_pmcid": "PMC12383969" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APP processing and A\u03b2 generation.", "mechanism": "Aberrant cleavage of glycosylated APP leads to \u03b2-amyloid plaque formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12383990" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates aggregation and toxicity.", "mechanism": "Accumulation of misfolded, glycosylated A\u03b2 peptides forms toxic plaques.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "O-glycosylation influences Tau aggregation.", "mechanism": "Hyperphosphorylated and glycosylated Tau forms neurofibrillary tangles.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation regulates IBA1 function in microglia.", "mechanism": "IBA1-positive microglia indicate CNS inflammation in AD.", "protein": "IBA1 (AIF1)", "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation modulates CRP stability and activity.", "mechanism": "Elevated CRP reflects systemic and CNS inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "O-glycosylation affects Tau solubility and aggregation.", "mechanism": "Tau pathology disrupts neuronal structure, leading to cognitive deficits.", "protein": "Tau protein", "relationship_type": "causal", "source_pmcid": "PMC12383990" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation status influences A\u03b2 clearance.", "mechanism": "A\u03b2 plaque deposition impairs synaptic function and memory.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12383990" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect IBA1-mediated immune response.", "mechanism": "Increased IBA1 marks microglial activation in AD brains.", "protein": "IBA1 (AIF1)", "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation required for IGF-1 secretion and function.", "mechanism": "Low IGF-1 associated with impaired neuroprotection and cognition.", "protein": "Insulin-like growth factor 1 (IGF-1)", "relationship_type": "protective", "source_pmcid": "PMC12383990" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation modulates IL-6 receptor binding.", "mechanism": "IL-6 elevation signals inflammatory processes in AD.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12383990" }, { "confidence": "high", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Adropin is a glycoprotein; glycosylation may affect stability and secretion, but specific glycan mechanism not detailed.", "mechanism": "Low circulating adropin predicts new onset AF in HFpEF patients; adropin deficiency linked to impaired metabolic adaptation, inflammation, and cardiac remodeling.", "protein": "Adropin", "protein_enriched": { "function": "Transcriptional activator (PubMed:15555580). Important for maintenance of pluripotency in embryonic stem cells (By similarity). Binds directly to the POU5F1 distal enhancer and the NANOG proximal prom", "gene_name": "ZNF322", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q6U7Q0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "high", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "Glycosylation may modulate adropin's bioactivity and stability.", "mechanism": "Low adropin levels associated with increased HF severity and adverse cardiac remodeling; adropin may protect against fibrosis and inflammation.", "protein": "Adropin", "protein_enriched": { "function": "Transcriptional activator (PubMed:15555580). Important for maintenance of pluripotency in embryonic stem cells (By similarity). Binds directly to the POU5F1 distal enhancer and the NANOG proximal prom", "gene_name": "ZNF322", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q6U7Q0" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12384010" }, { "confidence": "high", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "NT-proBNP is glycosylated; glycosylation may influence its plasma levels and diagnostic accuracy.", "mechanism": "Elevated NT-proBNP independently predicts new onset AF in HFpEF patients.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "high", "disease": "Heart failure with preserved ejection fraction (HFpEF)", "glycan_involvement": "Glycosylation status may affect NT-proBNP measurement and interpretation.", "mechanism": "NT-proBNP levels correlate with HF severity and risk of AF.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "sST2 is glycosylated; glycosylation may affect its function and detection.", "mechanism": "Elevated sST2 predicts new onset AF, reflecting cardiac fibrosis and remodeling.", "protein": "sST2", "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Galectin-3 binds \u03b2-galactosides; glycan interactions mediate its role in fibrosis.", "mechanism": "Galectin-3 is associated with cardiac fibrosis and remodeling, but not superior to NT-proBNP for AF prediction.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "hs-CRP is glycosylated; glycosylation affects its stability and function.", "mechanism": "Elevated hs-CRP reflects inflammation and predicts AF risk.", "protein": "hs-CRP", "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation may influence adropin's metabolic effects.", "mechanism": "Low adropin levels associated with increased risk and severity of T2DM; adropin regulates glucose and lipid metabolism.", "protein": "Adropin", "protein_enriched": { "function": "Transcriptional activator (PubMed:15555580). Important for maintenance of pluripotency in embryonic stem cells (By similarity). Binds directly to the POU5F1 distal enhancer and the NANOG proximal prom", "gene_name": "ZNF322", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q6U7Q0" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation may affect adropin's renal protective functions.", "mechanism": "Low adropin levels predict CKD and adverse outcomes.", "protein": "Adropin", "protein_enriched": { "function": "Transcriptional activator (PubMed:15555580). Important for maintenance of pluripotency in embryonic stem cells (By similarity). Binds directly to the POU5F1 distal enhancer and the NANOG proximal prom", "gene_name": "ZNF322", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q6U7Q0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384010" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation may modulate adropin's anti-fibrotic activity.", "mechanism": "Adropin inhibits TGF-\u03b2-induced fibroblast activation and fibrotic remodeling.", "protein": "Adropin", "protein_enriched": { "function": "Transcriptional activator (PubMed:15555580). Important for maintenance of pluripotency in embryonic stem cells (By similarity). Binds directly to the POU5F1 distal enhancer and the NANOG proximal prom", "gene_name": "ZNF322", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "Q6U7Q0" }, "relationship_type": "protective", "source_pmcid": "PMC12384010" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "AGR2 assists folding of glycosylated EGFR and mucins.", "mechanism": "AGR2 promotes EGFR folding and cell surface presentation, supporting tumor growth; upregulated in ER+ breast cancers.", "protein": "AGR2", "protein_enriched": { "function": "Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, c", "gene_name": "AGR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95994" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "ERp44 regulates folding/retention of glycoproteins in ER.", "mechanism": "ERp44 depletion exacerbates diabetic nephropathy and affects glucose/lipid metabolism.", "protein": "ERp44", "protein_enriched": { "function": "Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the ca", "gene_name": "ERP44", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO", "G58001LT", "G70994MS", "G29068FM" ], "uniprot_id": "Q9BS26" }, "relationship_type": "protective", "source_pmcid": "PMC12384036" }, { "confidence": "high", "disease": "Inflammatory bowel disease", "glycan_involvement": "AGR2 forms disulfide bonds with glycosylated mucins (MUC2).", "mechanism": "AGR2 deficiency impairs mucin folding, reducing mucus barrier and increasing inflammation.", "protein": "AGR2", "protein_enriched": { "function": "Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, c", "gene_name": "AGR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95994" }, "relationship_type": "causal", "source_pmcid": "PMC12384036" }, { "confidence": "high", "disease": "Cystic fibrosis-like disorder", "glycan_involvement": "Defective glycosylated mucin folding due to AGR2 loss.", "mechanism": "Biallelic AGR2 mutations decrease mucociliary machinery components.", "protein": "AGR2", "protein_enriched": { "function": "Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, c", "gene_name": "AGR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95994" }, "relationship_type": "causal", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Likely regulates folding of ciliary and cell surface glycoproteins.", "mechanism": "AGR3 overexpression promotes Wnt/\u03b2-catenin signaling and stemness, predicts poor survival.", "protein": "AGR3", "protein_enriched": { "function": "Required for calcium-mediated regulation of ciliary beat frequency and mucociliary clearance in the airway. Might be involved in the regulation of intracellular calcium in tracheal epithelial cells", "gene_name": "AGR3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8TD06" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Potential regulation of glycoprotein folding in ciliated cells.", "mechanism": "AGR3 expression in serous ovarian cancer predicts prolonged survival.", "protein": "AGR3", "protein_enriched": { "function": "Required for calcium-mediated regulation of ciliary beat frequency and mucociliary clearance in the airway. Might be involved in the regulation of intracellular calcium in tracheal epithelial cells", "gene_name": "AGR3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8TD06" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "ERp44 regulates folding/retention of glycoproteins.", "mechanism": "Honokiol induces ERp44 degradation, leading to tumor apoptosis.", "protein": "ERp44", "protein_enriched": { "function": "Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the ca", "gene_name": "ERP44", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO", "G58001LT", "G70994MS", "G29068FM" ], "uniprot_id": "Q9BS26" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Chronic myeloid leukemia", "glycan_involvement": "AGR2 may regulate folding of glycoproteins involved in leukemia cell survival.", "mechanism": "miR-217 downregulates AGR2, sensitizing cells to Dasatinib and reducing tumor burden.", "protein": "AGR2", "protein_enriched": { "function": "Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, c", "gene_name": "AGR2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95994" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "ERp44 regulates folding of glycoproteins in placental cells.", "mechanism": "miR-101 downregulates ERp44, modulating ER stress and trophoblast apoptosis.", "protein": "ERp44", "protein_enriched": { "function": "Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the ca", "gene_name": "ERP44", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO", "G58001LT", "G70994MS", "G29068FM" ], "uniprot_id": "Q9BS26" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384036" }, { "confidence": "medium", "disease": "Nephropathy", "glycan_involvement": "ERp44 controls ER retention/folding of glycoproteins relevant to kidney function.", "mechanism": "ERp44 depletion worsens nephropathy in diabetic mouse models.", "protein": "ERp44", "protein_enriched": { "function": "Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the ca", "gene_name": "ERP44", "glycan_count": 6, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G43417UB", "G49108TO", "G58001LT", "G70994MS", "G29068FM" ], "uniprot_id": "Q9BS26" }, "relationship_type": "protective", "source_pmcid": "PMC12384036" }, { "confidence": "high", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "ADAMTS1 is a secreted glycoprotein; glycosylation is essential for secretion and ECM interaction.", "mechanism": "Upregulation via GPER activation inhibits metastasis by modulating ECM and reducing invasiveness.", "protein": "ADAMTS1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384126" }, { "confidence": "high", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "GPER is a glycoprotein; glycosylation affects membrane localization and ligand binding.", "mechanism": "Activation induces p53 and ADAMTS1, leading to cell cycle arrest and inhibition of tumor growth/metastasis.", "protein": "GPER", "relationship_type": "protective", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation required for ECM degradation activity.", "mechanism": "Promotes tumor formation and metastasis.", "protein": "ADAMTS1", "relationship_type": "causal", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Glycosylation enables ECM remodeling.", "mechanism": "Suppresses lymphangiogenesis and metastasis.", "protein": "ADAMTS1", "relationship_type": "protective", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Renal cancer", "glycan_involvement": "Glycosylation required for protease activity.", "mechanism": "Promotes tumor formation and metastasis.", "protein": "ADAMTS1", "relationship_type": "causal", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation required for ECM interaction.", "mechanism": "Promotes tumor formation and metastasis.", "protein": "ADAMTS1", "relationship_type": "causal", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "Glycosylation of ADAMTS1 and EGFR affects signaling.", "mechanism": "ADAMTS1-L1CAM-EGFR axis drives EMT and lymph node metastasis.", "protein": "ADAMTS1", "relationship_type": "causal", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation required for ECM remodeling.", "mechanism": "Associated with suppression of hepatic fibrosis.", "protein": "ADAMTS1", "relationship_type": "protective", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Liver cancer (hepatocellular carcinoma)", "glycan_involvement": "E-cadherin glycosylation modulates cell adhesion.", "mechanism": "Upregulated by GPER/ADAMTS1, indicating epithelial phenotype and reduced metastasis.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384126" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "EGFR glycosylation affects receptor activation.", "mechanism": "ADAMTS1-L1CAM-EGFR axis promotes EMT and metastasis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12384126" }, { "confidence": "high", "disease": "Musculocontractural Ehlers\u2013Danlos syndrome (mcEDS)", "glycan_involvement": "DS chain covalently linked to decorin core protein is essential for ECM stability.", "mechanism": "Loss of DS glycosylation on decorin due to DSE/CHST14 mutations disrupts ECM integrity.", "protein": "Decorin", "relationship_type": "causal", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Musculocontractural Ehlers\u2013Danlos syndrome (mcEDS)", "glycan_involvement": "DS chains on biglycan regulate collagen fibril organization.", "mechanism": "Defective DS biosynthesis alters biglycan glycosylation, contributing to ECM defects.", "protein": "Biglycan", "relationship_type": "causal", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Cancer (colorectal, breast, pancreatic, lung)", "glycan_involvement": "DS glycosylation at Ser137 is required for endocan's pro-tumor functions.", "mechanism": "Endocan DS chain and core protein promote tumor growth, angiogenesis, and cell migration.", "protein": "Endocan", "protein_enriched": { "function": "Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP", "gene_name": "RANBP3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q9H6Z4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "DS glycan structure is critical for HCII activation.", "mechanism": "DS binding to HCII enhances thrombin inhibition, providing anticoagulant effect.", "protein": "Heparin cofactor II (HCII)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Musculocontractural Ehlers\u2013Danlos syndrome (mcEDS)", "glycan_involvement": "Epimerization of GlcA to IdoA in DS chain is disrupted.", "mechanism": "DSE1 mutations cause loss of DS biosynthesis, leading to connective tissue fragility.", "protein": "DS Epimerase 1 (DSE1)", "relationship_type": "causal", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Musculocontractural Ehlers\u2013Danlos syndrome (mcEDS)", "glycan_involvement": "4-O-sulfation of GalNAc in DS is essential for stable DS domains.", "mechanism": "CHST14 mutations abolish DS sulfation, resulting in loss of DS and ECM defects.", "protein": "Dermatan-4-O-sulfotransferase 1 (D4ST1)", "protein_enriched": { "function": "Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is d", "gene_name": "CHST11", "glycan_count": 3, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ", "G66537LK", "G49108TO" ], "uniprot_id": "Q9NPF2" }, "relationship_type": "causal", "source_pmcid": "PMC12384162" }, { "confidence": "medium", "disease": "Neurodegenerative disease", "glycan_involvement": "DS oligosaccharide acts as a signaling ligand for ALK.", "mechanism": "DS tetrasaccharide induces ALK autophosphorylation, promoting neuronal development.", "protein": "Anaplastic lymphoma kinase (ALK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384162" }, { "confidence": "medium", "disease": "Arthritis", "glycan_involvement": "DS sulfation pattern determines RAGE binding and activation.", "mechanism": "DS binds RAGE, modulating inflammatory signaling in arthritis.", "protein": "RAGE", "relationship_type": "biomarker", "source_pmcid": "PMC12384162" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "DS glycan augments IFN-\u03b3 signaling compared to core protein alone.", "mechanism": "DS stabilizes IFN-\u03b3 and enhances STAT1 activation, boosting anti-tumor immunity.", "protein": "Interferon gamma (IFN-\u03b3)", "protein_enriched": { "function": "Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing", "gene_name": "Ifng", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01580" }, "relationship_type": "protective", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Mucopolysaccharidosis type I (MPS-I)", "glycan_involvement": "DS glycan is not degraded, causing lysosomal accumulation.", "mechanism": "DS accumulation due to \u03b1-L-iduronidase deficiency leads to decorin storage.", "protein": "Decorin", "relationship_type": "biomarker", "source_pmcid": "PMC12384162" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "GPx1 reduces H2O2 and lipid hydroperoxides, limiting oxidative damage in neurons.", "protein": "Glutathione Peroxidase 1 (GPx1)", "relationship_type": "protective", "source_pmcid": "PMC12384178" }, { "confidence": "high", "disease": "Parkinson's Disease", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "GPx1 activity mitigates ROS-induced neuronal degeneration.", "protein": "Glutathione Peroxidase 1 (GPx1)", "relationship_type": "protective", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "TXNRD1 maintains redox homeostasis, delaying age-related cellular decline.", "protein": "Thioredoxin Reductase 1 (TXNRD1)", "relationship_type": "protective", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Neurocognitive Impairment", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "SELENOP delivers selenium to the brain, supporting antioxidant enzyme function.", "protein": "Selenoprotein P (SELENOP)", "relationship_type": "protective", "source_pmcid": "PMC12384178" }, { "confidence": "high", "disease": "Aging", "glycan_involvement": "Not a glycoprotein.", "mechanism": "GSH directly scavenges ROS and supports detoxifying enzymes.", "protein": "Glutathione (GSH)", "relationship_type": "protective", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Aging", "glycan_involvement": "Glycosylation may affect folding and stability.", "mechanism": "PDI redox-sensitive cysteine residues act as switches in protein folding and redox signaling.", "protein": "Protein Disulfide Isomerase (PDI)", "relationship_type": "biomarker", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Neurodegeneration", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "DNMT1 mutants aggregate and lose heterochromatin interaction, leading to neuronal degeneration.", "protein": "DNMT1", "protein_enriched": { "function": "Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ess", "gene_name": "DNMT1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G28541PG", "G49108TO" ], "uniprot_id": "P26358" }, "relationship_type": "causal", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "DNMT3A mutations linked to increased pro-inflammatory cytokines and persistent inflammation.", "protein": "DNMT3A", "protein_enriched": { "function": "Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation ", "gene_name": "DNMT3A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6K1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384178" }, { "confidence": "medium", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "No direct glycosylation role mentioned.", "mechanism": "SEPHS2 disruption impairs GPX4 synthesis, increases ROS, and sensitizes cells to ferroptosis.", "protein": "SEPHS2", "relationship_type": "causal", "source_pmcid": "PMC12384178" }, { "confidence": "low", "disease": "Chronic Inflammation", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "Prx cysteine modifications regulate redox signaling in inflammation.", "protein": "Peroxiredoxin (Prx)", "relationship_type": "biomarker", "source_pmcid": "PMC12384178" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Not specified", "mechanism": "Elevated SOD1 activity supports tumor survival under oxidative stress; SOD1 levels correlate with prognosis and treatment response.", "protein": "SOD1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "SOD3 is an extracellular glycoprotein; glycosylation may affect secretion and stability.", "mechanism": "Upregulation of SOD3 reduces tumor development and metastasis; SOD3 levels have diagnostic and prognostic value.", "protein": "SOD3", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Skin cancer", "glycan_involvement": "Not specified", "mechanism": "Mn-SOD (SOD2) deficiency increases oxidative stress and tumorigenesis; overexpression inhibits tumor development.", "protein": "SOD2", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Glioma/Glioblastoma", "glycan_involvement": "Not specified", "mechanism": "SOD1 overexpression increases tumor survival and resistance to therapy; inhibition sensitizes cells to oxidative stress.", "protein": "SOD1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384489" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Not specified", "mechanism": "SOD2 overexpression reduces apoptosis and supports tumor growth; targeting SOD2 can reduce tumor progression.", "protein": "SOD2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Oral cancer", "glycan_involvement": "Not specified", "mechanism": "Reduced SOD1 levels in serum and tissue are associated with oral cancer progression and may serve as diagnostic/prognostic markers.", "protein": "SOD1", "relationship_type": "biomarker", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "Not specified", "mechanism": "SOD1 is overexpressed in NSCLC, promoting proliferation and survival; its inhibition induces apoptosis.", "protein": "SOD1", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "SOD3 is an extracellular glycoprotein; glycosylation may affect function.", "mechanism": "SOD3 expression is decreased in lung cancer, indicating loss of extracellular antioxidant defense and worse prognosis.", "protein": "SOD3", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12384489" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Not specified", "mechanism": "SOD2 is elevated in gastric cancer and associated with poor prognosis; H. pylori infection increases SOD2 via NF-\u03baB.", "protein": "SOD2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12384489" }, { "confidence": "medium", "disease": "Antineutrophil cytoplasmic antibody-associated vasculitis (AAV)", "glycan_involvement": "Not specified", "mechanism": "Lower SOD1 levels reflect increased oxidative stress and inflammation; SOD1 inversely correlates with disease activity markers.", "protein": "SOD1", "relationship_type": "biomarker", "source_pmcid": "PMC12384489" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "RAGE N-glycosylation modulates S100B binding and signaling.", "mechanism": "Overexpressed by reactive astrocytes near amyloid plaques; activates RAGE and ERK1/2, upregulates BACE1, promotes A\u03b2 production and tau hyperphosphorylation.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "RAGE glycosylation affects ligand recognition.", "mechanism": "Upregulated; forms heterodimers that interact with A\u03b2, enhancing aggregation and plaque maturation.", "protein": "S100A8/A9", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "RAGE glycosylation required for S100B signaling.", "mechanism": "Elevated in substantia nigra; activates RAGE/NF-\u03baB, induces iNOS/COX-2, increases NO/ROS, promotes dopaminergic neuron death and \u03b1-synuclein aggregation.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "RAGE glycosylation modulates S100A8/A9 signaling.", "mechanism": "Upregulated in active lesions; binds TLR4/RAGE, activates NF-\u03baB/p38, induces chemokines (CCL2, CXCL10), recruits Th1/Th17 cells, promotes demyelination.", "protein": "S100A8/A9", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12384525" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "RAGE glycosylation may influence S100B-mediated signaling.", "mechanism": "Accumulated in astrocytes and motor neurons; associated with oxidative stress, BBB disruption, and maladaptive stress response.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384525" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "RAGE glycosylation may affect interaction.", "mechanism": "Interacts with mutant SOD1, contributing to neurodegenerative processes.", "protein": "S100A8/A9", "relationship_type": "causal", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Traumatic brain injury", "glycan_involvement": "RAGE glycosylation required for S100B signaling.", "mechanism": "Released by astrocytes post-injury; reflects metabolic stress and tissue damage, promotes neuroinflammation.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384525" }, { "confidence": "medium", "disease": "Traumatic brain injury", "glycan_involvement": "Potential RAGE glycosylation involvement.", "mechanism": "Detected in astrocytes/neurons; modulate Ca2+ signaling, oxidative stress, and glial activation.", "protein": "S100A4/S100A6/S100A8", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "General neuroinflammation", "glycan_involvement": "RAGE N-glycosylation critical for ligand binding and signaling.", "mechanism": "Acts as DAMP; activates RAGE/TLRs, triggers NF-\u03baB/MAPK, induces cytokines, glial activation, BBB disruption.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Neurodegenerative diseases (AD, PD, MS, ALS)", "glycan_involvement": "N-glycosylation at extracellular domains essential for S100 ligand recognition and downstream signaling.", "mechanism": "Glycosylated receptor mediates S100 protein-induced pro-inflammatory signaling; central to disease progression.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384525" }, { "confidence": "high", "disease": "Hemorrhagic disorder", "glycan_involvement": "\u03b12PI is a glycoprotein; glycosylation may affect stability and plasma levels.", "mechanism": "Congenital deficiency of \u03b12PI leads to increased fibrinolysis and severe bleeding.", "protein": "Alpha2-plasmin inhibitor", "relationship_type": "causal", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation may influence \u03b12PI plasma levels and function.", "mechanism": "Elevated total \u03b12PI and NPB-\u03b12PI levels are independently associated with increased VTE risk.", "protein": "Alpha2-plasmin inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "C-terminal truncation may affect glycosylation and binding properties.", "mechanism": "Elevated NPB-\u03b12PI (non-plasminogen binding form) increases clot lysis time and alters clot structure, contributing to thrombosis risk.", "protein": "Alpha2-plasmin inhibitor (NPB-\u03b12PI variant)", "relationship_type": "causal", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation may affect cross-linking efficiency.", "mechanism": "PB-\u03b12PI (plasminogen binding form) is efficiently cross-linked to fibrin by FXIII, preventing premature clot dissolution.", "protein": "Alpha2-plasmin inhibitor (PB-\u03b12PI variant)", "relationship_type": "protective", "source_pmcid": "PMC12384537" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation status may influence \u03b12PI stability and plasma levels.", "mechanism": "Decreased full-length \u03b12PI levels reported in male MI survivors; altered \u03b12PI may affect fibrinolysis.", "protein": "Alpha2-plasmin inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "C-terminal truncation may alter glycosylation and function.", "mechanism": "NPB-\u03b12PI levels are independently associated with VTE risk (OR: 9.868).", "protein": "Alpha2-plasmin inhibitor (NPB-\u03b12PI variant)", "relationship_type": "biomarker", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation may modulate clot incorporation and structure.", "mechanism": "Altered \u03b12PI incorporation into clots (especially NPB-\u03b12PI) increases fibrin fiber thickness and reduces pore size, decreasing fibrinolytic capacity.", "protein": "Alpha2-plasmin inhibitor", "relationship_type": "causal", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Hemorrhagic disorder", "glycan_involvement": "Glycosylation may affect \u03b12PI activity and plasma half-life.", "mechanism": "Low \u03b12PI activity or antigen levels indicate increased bleeding risk due to insufficient plasmin inhibition.", "protein": "Alpha2-plasmin inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC12384537" }, { "confidence": "medium", "disease": "Venous thromboembolism", "glycan_involvement": "Glycosylation may affect PB-\u03b12PI cross-linking to fibrin.", "mechanism": "PB-\u03b12PI incorporation into clots correlates with FXIII activity and fibrinogen levels, influencing clot stability.", "protein": "Alpha2-plasmin inhibitor (PB-\u03b12PI variant)", "relationship_type": "biomarker", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Venous thromboembolism", "glycan_involvement": "C-terminal truncation may impact glycosylation and non-covalent binding.", "mechanism": "NPB-\u03b12PI binds non-covalently to fibrin, prolongs clot lysis time, and modifies clot structure, contributing to thrombosis.", "protein": "Alpha2-plasmin inhibitor (NPB-\u03b12PI variant)", "relationship_type": "causal", "source_pmcid": "PMC12384537" }, { "confidence": "high", "disease": "Ferroptosis", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Transferrin delivers iron to cells; excess iron promotes oxidative stress and ferroptosis in retinal pigment epithelium (RPE).", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "causal", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Retinitis Pigmentosa (RP)", "glycan_involvement": "N-glycosylation critical for proper folding and trafficking.", "mechanism": "Mutations in rhodopsin gene cause misfolding, ER stress, and photoreceptor death.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "causal", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor signaling.", "mechanism": "AGE-RAGE interaction triggers inflammation, oxidative stress, and vascular dysfunction in DR.", "protein": "RAGE", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Age-related Macular Degeneration (AMD)", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "VEGF-A upregulation drives neovascularization in AMD.", "protein": "VEGF-A", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Photoreceptor Degeneration", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "GPX4 prevents lipid peroxidation and ferroptosis in photoreceptors.", "protein": "GPX4", "relationship_type": "protective", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Age-related Macular Degeneration (AMD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "GPX1 reduces oxidative stress; mutations lower antioxidant capacity and increase AMD risk.", "protein": "GPX1", "relationship_type": "protective", "source_pmcid": "PMC12384684" }, { "confidence": "medium", "disease": "Age-related Macular Degeneration (AMD)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "GR regenerates GSH; reduced activity correlates with increased AMD risk.", "protein": "GR", "relationship_type": "protective", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Photoreceptor Degeneration", "glycan_involvement": "Not a glycoprotein.", "mechanism": "TXN reduces oxidative stress and inhibits apoptosis in photoreceptors.", "protein": "TXN", "protein_enriched": { "function": "Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:17182577, PubMed:1903223", "gene_name": "TXN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P10599" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12384684" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "GLRX1 overexpression in diabetic retina enhances NF-\u03baB activation and inflammation.", "protein": "GLRX1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12384684" }, { "confidence": "medium", "disease": "Diabetic Retinopathy (DR)", "glycan_involvement": "Not a glycoprotein.", "mechanism": "Aldose reductase activity depletes NADPH, increases oxidative stress, and promotes DR.", "protein": "Aldose Reductase", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12384684" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Insulin is N-glycosylated, which affects its stability and receptor interaction.", "mechanism": "Elevated insulin levels indicate insulin resistance, common in obesity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Morbid obesity", "glycan_involvement": "Glycosylation modulates insulin's half-life and bioactivity.", "mechanism": "Hyperinsulinemia promotes fat storage and weight gain.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12384771" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "SHBG is N-glycosylated; glycosylation affects its serum levels and function.", "mechanism": "Low SHBG levels are associated with insulin resistance and obesity.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Morbid obesity", "glycan_involvement": "Altered glycosylation may contribute to decreased SHBG in obesity.", "mechanism": "Obesity is associated with reduced SHBG, reflecting metabolic dysfunction.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "HbA1c reflects chronic hyperglycemia and risk for diabetes.", "protein": "Glycosylated hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Higher HDL is protective against cardiovascular disease; increased by intervention.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB) with N-glycosylation affecting clearance.", "mechanism": "Elevated LDL is a risk factor for cardiovascular disease.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation status may influence insulin's metabolic effects.", "mechanism": "Hyperinsulinemia is a core feature of metabolic syndrome.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "N-glycosylation modulates SHBG's serum stability.", "mechanism": "Low SHBG is linked to increased risk of metabolic syndrome.", "protein": "SHBG", "relationship_type": "biomarker", "source_pmcid": "PMC12384771" }, { "confidence": "low", "disease": "Low-grade inflammation", "glycan_involvement": "Glycosylation may modulate insulin's immunomodulatory effects.", "mechanism": "Insulin resistance promotes chronic low-grade inflammation in obesity.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12384771" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Reduces GST-P-positive foci, inhibits cell proliferation (\u2193PCNA), induces apoptosis (\u2191TUNEL, \u2191BAX, \u2191CASP3)", "protein": "Glutelin Hydrolysate (GTLH)", "relationship_type": "protective", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Reduces ACF, inhibits cell proliferation (\u2193PCNA), induces apoptosis (\u2191TUNEL, \u2191BAX)", "protein": "Glutelin Hydrolysate (GTLH)", "relationship_type": "protective", "source_pmcid": "PMC12384901" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Reduces GST-P-positive foci, inhibits cell proliferation (\u2193PCNA)", "protein": "Glutelin", "relationship_type": "protective", "source_pmcid": "PMC12384901" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Inhibits cell proliferation (\u2193PCNA)", "protein": "Glutelin", "relationship_type": "protective", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "GSTs may be glycosylated, but not discussed here", "mechanism": "GST-P-positive foci indicate preneoplastic lesions in liver carcinogenesis", "protein": "Glutathione S-transferase placental form (GST-P)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15636" }, "relationship_type": "biomarker", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "ACF are preneoplastic lesions marking early colon carcinogenesis", "protein": "Aberrant crypt foci (ACF)", "relationship_type": "biomarker", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "PCNA is known to be O-glycosylated, but not discussed here", "mechanism": "PCNA-positive cells indicate increased cell proliferation in liver carcinogenesis", "protein": "Proliferating Cell Nuclear Antigen (PCNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "PCNA is known to be O-glycosylated, but not discussed here", "mechanism": "PCNA-positive cells indicate increased cell proliferation in colon carcinogenesis", "protein": "Proliferating Cell Nuclear Antigen (PCNA)", "relationship_type": "biomarker", "source_pmcid": "PMC12384901" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Upregulation of BAX promotes apoptosis in liver preneoplastic lesions", "protein": "Bcl-2-associated X protein (BAX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384901" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "No direct glycosylation mechanism described", "mechanism": "Upregulation of CASP3 promotes apoptosis in liver preneoplastic lesions", "protein": "Caspase-3 (CASP3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12384901" }, { "confidence": "high", "disease": "Epidermal cyst", "glycan_involvement": "Possible glycosylation of keratin 5 observed as higher molecular weight band; may affect protein stability or function.", "mechanism": "Persistent keratin 5 expression in subcutaneously implanted non\u2013de-epithelialized flaps leads to ongoing keratinocyte differentiation and cyst formation.", "protein": "Keratin 5", "relationship_type": "causal", "source_pmcid": "PMC12385113" }, { "confidence": "medium", "disease": "Infection", "glycan_involvement": "Glycosylation may influence keratin 5's role in cyst wall integrity and immune response.", "mechanism": "Residual epidermal components expressing keratin 5 can form cysts that may become infected postoperatively.", "protein": "Keratin 5", "relationship_type": "causal", "source_pmcid": "PMC12385113" }, { "confidence": "low", "disease": "Skin necrosis", "glycan_involvement": "Not directly discussed.", "mechanism": "Keratin 5 expression marks persistent epidermal tissue, which may be exposed in necrotic skin flaps.", "protein": "Keratin 5", "relationship_type": "biomarker", "source_pmcid": "PMC12385113" }, { "confidence": "medium", "disease": "Epidermal cyst", "glycan_involvement": "Not specified.", "mechanism": "Residual HFSCs in de-epithelialized flaps can transiently form small cysts, which regress over time.", "protein": "Hair Follicle Stem Cell Markers (HFSCs)", "relationship_type": "causal", "source_pmcid": "PMC12385113" }, { "confidence": "low", "disease": "Pilonidal sinus", "glycan_involvement": "Not specified.", "mechanism": "Subcutaneous hair follicles may contribute to pilonidal sinus formation if free hairs escape cyst encapsulation.", "protein": "Hair Follicle Stem Cell Markers (HFSCs)", "relationship_type": "causal", "source_pmcid": "PMC12385113" }, { "confidence": "medium", "disease": "Alopecia (pressure-induced)", "glycan_involvement": "Not specified.", "mechanism": "Subcutaneous environment suppresses HFSC signaling, leading to diminished hair growth and possible alopecia.", "protein": "Hair Follicle Stem Cell Markers (HFSCs)", "relationship_type": "causal", "source_pmcid": "PMC12385113" }, { "confidence": "medium", "disease": "Alopecia (pressure-induced)", "glycan_involvement": "Not specified.", "mechanism": "Decline in keratin 5 expression correlates with suppressed hair follicle activity and hair loss.", "protein": "Keratin 5", "relationship_type": "biomarker", "source_pmcid": "PMC12385113" }, { "confidence": "high", "disease": "Epidermal cyst", "glycan_involvement": "Possible glycosylation may affect detection and function.", "mechanism": "Keratin 5 is a marker for basal epidermal cells present in cyst walls.", "protein": "Keratin 5", "relationship_type": "biomarker", "source_pmcid": "PMC12385113" }, { "confidence": "low", "disease": "Infection", "glycan_involvement": "Not specified.", "mechanism": "Keratin 5-positive cysts may be prone to infection due to retained epidermal tissue.", "protein": "Keratin 5", "relationship_type": "biomarker", "source_pmcid": "PMC12385113" }, { "confidence": "medium", "disease": "Epidermal cyst", "glycan_involvement": "Glycosylation status may influence therapeutic targeting.", "mechanism": "Reducing keratin 5 expression via de-epithelialization decreases cyst formation risk.", "protein": "Keratin 5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385113" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "ABCG2 is glycosylated, affecting trafficking and function.", "mechanism": "Promotes uric acid excretion; upregulation by MYPs enhances UA clearance.", "protein": "ABCG2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation modulates URAT1 stability and localization.", "mechanism": "Facilitates renal UA reabsorption; downregulation by MYPs reduces UA retention.", "protein": "URAT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "GLUT9 glycosylation affects membrane targeting.", "mechanism": "Mediates UA reabsorption; MYPs suppress expression, lowering serum UA.", "protein": "GLUT9", "protein_enriched": { "function": "High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a r", "gene_name": "SLC2A9", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRM0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "Glycosylation influences XOD stability and activity.", "mechanism": "Catalyzes UA synthesis; MYPs inhibit XOD activity, reducing UA production.", "protein": "Xanthine oxidase (XOD)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385240" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "NLRP3 glycosylation may affect inflammasome assembly.", "mechanism": "Activates inflammasome; upregulated in HUA, suppressed by MYPs.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12385240" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "ASC glycosylation impacts protein-protein interactions.", "mechanism": "Inflammasome adaptor; increased in HUA, reduced by MYPs.", "protein": "ASC", "relationship_type": "causal", "source_pmcid": "PMC12385240" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation may regulate caspase-1 activation.", "mechanism": "Processes IL-1\u03b2; activated in HUA, suppressed by MYPs.", "protein": "Caspase-1", "relationship_type": "causal", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Pro-inflammatory cytokine; elevated in HUA/gout, reduced by MYPs.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "N-glycosylation modulates IL-6 stability.", "mechanism": "Cytokine; increased in HUA, suppressed by MYPs.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 receptor binding.", "mechanism": "Cytokine; elevated in HUA, reduced by MYPs.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12385240" }, { "confidence": "high", "disease": "Elite speed\u2013power athletic phenotype", "glycan_involvement": "O-glycosylation of neural proteins, affecting neuromuscular function", "mechanism": "rs10196189 G allele increases GALNT13 expression in brain, associated with athlete status", "protein": "GALNT13", "relationship_type": "biomarker", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Familial tumoral calcinosis", "glycan_involvement": "Defective O-glycosylation disrupts protein function", "mechanism": "Missense mutations impair enzyme function, leading to abnormal phosphate metabolism and calcification", "protein": "GALNT13", "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Hyperostosis\u2013hyperphosphatemia syndrome", "glycan_involvement": "Impaired O-glycosylation", "mechanism": "Predicted missense mutations impair glycosylation, affecting phosphate metabolism", "protein": "GALNT13", "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Tumor-like calcification", "glycan_involvement": "Disrupted O-glycosylation", "mechanism": "Mutations reduce enzymatic activity, leading to abnormal calcification", "protein": "GALNT13", "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Elite speed\u2013power athletic phenotype", "glycan_involvement": "O-glycosylation modulates muscle energetics", "mechanism": "rs558129 T allele enriched in athletes, associated with higher anaerobic power", "protein": "GALNTL6", "protein_enriched": { "function": "Dual methyltransferase that catalyzes methylation of elongation factor 1-alpha (EEF1A1 and EEF1A2) at two different positions, and is therefore involved in the regulation of mRNA translation (PubMed:3", "gene_name": "METTL13", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q8N6R0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385310" }, { "confidence": "high", "disease": "Hereditary spastic paraplegia type 26 (HSP26)", "glycan_involvement": "Defective N-glycosylation", "mechanism": "Mutations impair N-glycan processing, leading to neurodegeneration", "protein": "B4GALNT1", "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Autism spectrum disorder", "glycan_involvement": "Impaired N-glycosylation", "mechanism": "Dysfunction affects N-glycan maturation, impacting neurodevelopment", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "medium", "disease": "Cognitive impairment", "glycan_involvement": "N-glycosylation defects", "mechanism": "Defective enzyme activity disrupts glycan processing in brain", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "high", "disease": "Congenital disorders of glycosylation (CDG)", "glycan_involvement": "N-glycosylation impairment", "mechanism": "Mutations lead to global glycosylation defects", "protein": "MAN2A2", "protein_enriched": { "function": "Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart", "gene_name": "TBX20", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UMR3" }, "relationship_type": "causal", "source_pmcid": "PMC12385310" }, { "confidence": "low", "disease": "Medial gastrocnemius muscle thickness (structural trait)", "glycan_involvement": "O-glycosylation may affect muscle architecture", "mechanism": "G allele nominally associated with increased muscle thickness", "protein": "GALNT13", "relationship_type": "biomarker", "source_pmcid": "PMC12385310" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin; not classical glycosylation.", "mechanism": "Reflects average blood glucose via glycation of hemoglobin.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385379" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Indirect; reflects glycoprotein metabolism.", "mechanism": "Elevated FBG indicates impaired glucose metabolism.", "protein": "Fasting Blood Glucose (FBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "TGF-\u03b2 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "Altered TGF-\u03b2/Smad signaling promotes cardiac fibrosis in diabetes.", "protein": "Transforming Growth Factor Beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Diabetic Cardiomyopathy", "glycan_involvement": "Potential O-glycosylation modulates signaling.", "mechanism": "Smad signaling mediates TGF-\u03b2 effects in diabetic heart tissue.", "protein": "Smad proteins", "relationship_type": "causal", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Glycosylation may regulate NF-\u03baB pathway components.", "mechanism": "NF-\u03baB activation drives inflammation in T2D.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Glycosylation of receptors modulates pathway activation.", "mechanism": "PI3K/AKT signaling regulates insulin sensitivity.", "protein": "PI3K/AKT pathway proteins", "relationship_type": "causal", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Glycosylation may affect AMPK stability and activity.", "mechanism": "AMPK activation improves glucose uptake and metabolism.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects receptor binding.", "mechanism": "Elevated LDL-C is associated with increased T2D risk and complications.", "protein": "Low-Density Lipoprotein Cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "HDL is a glycoprotein; glycosylation influences function.", "mechanism": "Low HDL-C is a risk factor for T2D and cardiovascular complications.", "protein": "High-Density Lipoprotein Cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2D)", "glycan_involvement": "Associated with glycoprotein metabolism.", "mechanism": "Elevated TG reflects dyslipidemia in T2D.", "protein": "Triglycerides (TG)", "relationship_type": "biomarker", "source_pmcid": "PMC12385379" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Glycosylation affects fibrin polymerization and cell interactions.", "mechanism": "Fibrinogen deposition promotes fibroblast activation and ECM remodeling.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Arrhythmogenic disorders", "glycan_involvement": "Glycosylation modulates trafficking and stability of connexin 43.", "mechanism": "Reduced or mislocalized connexin 43 impairs electrical coupling, predisposing to arrhythmias.", "protein": "Connexin 43", "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation required for receptor binding and signaling.", "mechanism": "Neuregulin-ErbB signaling supports cardiomyocyte survival and repair.", "protein": "Neuregulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "N-glycosylation essential for VEGF secretion and activity.", "mechanism": "VEGF promotes angiogenesis and tissue repair after ischemia.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385601" }, { "confidence": "low", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation critical for laminin matrix assembly.", "mechanism": "Defective laminin impairs cardiac morphogenesis.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Progressive myocardial fibrosis", "glycan_involvement": "Glycosylation modulates fibronectin-cell interactions.", "mechanism": "Fibronectin accumulation drives fibroblast activation and ECM deposition.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "low", "disease": "Valve fibrosis and calcification", "glycan_involvement": "Glycosylation affects collagen assembly and ECM stability.", "mechanism": "Collagen VI maintains tissue structure; its dysregulation leads to fibrosis.", "protein": "Collagen VI", "protein_enriched": { "function": "Collagen VI acts as a cell-binding protein", "gene_name": "COL6A1", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07246CJ", "G11314AS", "G23719VF", "G23863VK", "G27058EU", "G27915IV", "G31852PQ", "G39188ZX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46503DX", "G59626AS", "G60033FS", "G62765YT", "G64527OM", "G70101JE", "G70223PD", "G70441OD", "G80920RR", "G84452RH", "G87661QW", "G90659AW", "G95177YH", "G29184RN", "G36442WJ", "G45504EY", "G47702MW", "G47950XN", "G63041LO", "G96091TT", "G10256JP", "G83460ZZ", "G43417UB", "G00912UN", "G01650EU", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G11870QZ", "G11911BT", "G18647XP", "G23294PN", "G23453IV", "G25451PN", "G28541PG", "G29299MO", "G33609NS", "G37399XV", "G39446WN", "G41840AI", "G46691LC", "G46902YN", "G47012YE", "G47644PP", "G48414YA", "G50045TK", "G51640FO", "G57317CE", "G57776ZU", "G59924QI", "G65184UU", "G72291OX", "G72735IY", "G72747WU", "G72790NZ", "G75983OB", "G80223IX", "G82119TF", "G82463GQ", "G82830MN", "G83229XP", "G84820NF", "G92050GC", "G92406TI", "G95865ZB", "G49108TO" ], "uniprot_id": "P12109" }, "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Congenital heart disease", "glycan_involvement": "O-fucosylation of Notch is required for ligand binding.", "mechanism": "Notch signaling is essential for valve and septal development.", "protein": "Notch", "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "low", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation modulates BMP secretion and receptor interaction.", "mechanism": "BMP signaling regulates cardiac morphogenesis.", "protein": "BMP", "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "medium", "disease": "Cardiac fibrosis", "glycan_involvement": "Indirect; ECM glycoprotein remodeling alters mechanotransduction.", "mechanism": "Persistent YAP activation drives fibroblast-to-myofibroblast transition.", "protein": "YAP", "relationship_type": "causal", "source_pmcid": "PMC12385601" }, { "confidence": "high", "disease": "Multidrug resistance", "glycan_involvement": "N-glycosylation critical for membrane localization and function.", "mechanism": "Facilitates efflux of drugs, reducing efficacy of antileishmanial agents.", "protein": "P-glycoprotein (MDR1/ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Potential glycosylation may affect enzyme stability and drug binding.", "mechanism": "Targeted by meglumine antimoniate, disrupting parasite redox balance.", "protein": "Trypanothione reductase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFJ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Glycosylation may modulate enzyme activity and drug sensitivity.", "mechanism": "Inhibition disrupts ergosterol biosynthesis in Leishmania.", "protein": "CYP51 (Sterol 14\u03b1-demethylase)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4QFJ1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Potential glycosylation may influence enzyme stability.", "mechanism": "Targeted by MA, interfering with parasite oxidative stress defense.", "protein": "FeSODA (Iron superoxide dismutase A)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "FESODA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A4HTI0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Glycosylation affects enzyme secretion and activity.", "mechanism": "Used to monitor parasite growth and drug efficacy in vitro.", "protein": "Acid phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Surface glycosylation mediates parasite entry and immune response.", "mechanism": "Serve as host cells for Leishmania amastigote infection.", "protein": "RAW 264.7 cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Ulcerative skin lesions", "glycan_involvement": "Glycosylation supports cell-cell adhesion and barrier function.", "mechanism": "Keratinocyte integrity maintained by MA-gel, preventing cytotoxicity.", "protein": "HaCaT keratinocyte glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385701" }, { "confidence": "high", "disease": "Cutaneous leishmaniasis", "glycan_involvement": "Interacts with glycoproteins via hydrogen bonding, not glycosylated.", "mechanism": "Acts as drug carrier, enhances skin retention and local drug delivery.", "protein": "Pluronic F127 (P407)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Superinfection", "glycan_involvement": "Surface glycosylation mediates host-pathogen interactions.", "mechanism": "Potential for secondary infection at lesion site if gel is contaminated.", "protein": "Staphylococcus aureus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385701" }, { "confidence": "medium", "disease": "Superinfection", "glycan_involvement": "Surface glycosylation mediates host-pathogen interactions.", "mechanism": "Potential for secondary infection at lesion site if gel is contaminated.", "protein": "Pseudomonas aeruginosa surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385701" }, { "confidence": "high", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation affects ABC transporter stability and trafficking.", "mechanism": "Suppression of ABC transporter activity impairs lipid export, promoting hepatic lipid accumulation.", "protein": "ABC transporters", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Lipid accumulation", "glycan_involvement": "Glycosylation modulates FATP2 membrane localization.", "mechanism": "Overexpression of FATP2 increases fatty acid uptake, contributing to hepatic steatosis.", "protein": "FATP2", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "N-glycosylation regulates CD36 function and lipid binding.", "mechanism": "CD36-mediated lipid uptake drives steatosis in NP-exposed livers.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "high", "disease": "Hepatocellular injury", "glycan_involvement": "Glycosylation influences ALT secretion and stability.", "mechanism": "Elevated ALT indicates liver cell damage following NP exposure.", "protein": "Aminotransferases (ALT)", "relationship_type": "biomarker", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Metabolic disorder", "glycan_involvement": "Glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Dysregulation of glycerophospholipid metabolism leads to altered membrane composition and metabolic dysfunction.", "protein": "Glycerophospholipid metabolism enzymes", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation is essential for complex assembly and function.", "mechanism": "NP exposure disrupts oxidative phosphorylation, causing mitochondrial dysfunction.", "protein": "Mitochondrial electron transport chain complexes", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Impaired nutrient absorption", "glycan_involvement": "Glycosylation required for enzyme activity and intestinal localization.", "mechanism": "NP-induced suppression of protein digestion enzymes reduces amino acid availability.", "protein": "Protein digestion and absorption enzymes", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Retinol metabolism disorder", "glycan_involvement": "Glycosylation modulates enzyme activity and substrate binding.", "mechanism": "Altered retinol metabolism (elevated 9-cis-retinal) disrupts vitamin A homeostasis.", "protein": "Retinol metabolism enzymes", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "medium", "disease": "Amino acid metabolism disorder", "glycan_involvement": "Glycosylation affects transporter trafficking and substrate specificity.", "mechanism": "NP exposure reduces essential amino acid transport, leading to metabolic imbalance.", "protein": "Amino acid transporters", "relationship_type": "causal", "source_pmcid": "PMC12385707" }, { "confidence": "low", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation may regulate Rubicon stability and function.", "mechanism": "CRISPR-Cas9 targeting of Rubicon modulates lipid metabolism and steatosis.", "protein": "Rubicon", "protein_enriched": { "function": "RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869)", "gene_name": "NAT10", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO", "G62765YT" ], "uniprot_id": "Q9H0A0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385707" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects SCD1 stability and localization.", "mechanism": "Upregulation of SCD1 promotes monounsaturated fatty acid synthesis, increasing triglyceride formation and fat storage.", "protein": "Stearoyl-CoA desaturase 1 (SCD1)", "relationship_type": "causal", "source_pmcid": "PMC12385762" }, { "confidence": "high", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "Glycosylation may regulate SCD1 activity in hepatocytes.", "mechanism": "SCD1 activity increases hepatic lipid accumulation via enhanced MUFA synthesis.", "protein": "Stearoyl-CoA desaturase 1 (SCD1)", "relationship_type": "causal", "source_pmcid": "PMC12385762" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation modulates receptor function and ligand binding.", "mechanism": "PPAR\u03b1 activation improves lipid metabolism and reduces serum triglycerides.", "protein": "Peroxisome proliferator-activated receptor alpha (PPAR\u03b1)", "protein_enriched": { "function": "Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethano", "gene_name": "Ppara", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P23204" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385762" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "N-glycosylation is essential for LDLR folding and function.", "mechanism": "LDLR mediates hepatic uptake of LDL cholesterol; dysfunction leads to elevated LDL-C.", "protein": "Low-density lipoprotein receptor (LDLR)", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "Ldlr", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P35951" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385762" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycoprotein components of HDL influence its anti-inflammatory properties.", "mechanism": "HDL facilitates reverse cholesterol transport, reducing atherosclerosis risk.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12385762" }, { "confidence": "medium", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "Glycosylation of apolipoproteins affects VLDL assembly and secretion.", "mechanism": "VLDL secretion reflects hepatic lipid export; reduced VLDL indicates impaired lipid handling.", "protein": "Very low-density lipoprotein (VLDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12385762" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation may affect enzyme stability in serum.", "mechanism": "Elevated ALT indicates hepatocellular damage.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385762" }, { "confidence": "high", "disease": "Liver injury", "glycan_involvement": "Glycosylation influences AST serum half-life.", "mechanism": "Elevated AST is a marker of liver and tissue injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385762" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation is required for RBP4 secretion.", "mechanism": "Elevated RBP4 is associated with impaired insulin sensitivity.", "protein": "Retinol-binding protein 4 (RBP4)", "protein_enriched": { "function": "Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, l", "gene_name": "SORD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G49108TO" ], "uniprot_id": "Q00796" }, "relationship_type": "biomarker", "source_pmcid": "PMC12385762" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation modulates enzyme activity and hormone production.", "mechanism": "Altered steroid biosynthesis affects metabolic homeostasis.", "protein": "Steroid hormone biosynthesis enzymes", "relationship_type": "causal", "source_pmcid": "PMC12385762" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Polyphenol-protein conjugates may include glycan moieties affecting solubility and bioactivity.", "mechanism": "Theabrownins bind bile acids, reducing cholesterol absorption and promoting lipid-lowering effects.", "protein": "Theabrownins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation increases solubility and stability, enhancing protective effects.", "mechanism": "Glycosylated flavonoids have improved bioavailability and antioxidant properties, reducing cardiovascular risk.", "protein": "Flavonoid glycosides", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation may modulate peptide stability and activity.", "mechanism": "Bioactive peptides generated during fermentation may improve insulin sensitivity and glucose metabolism.", "protein": "Peptides (glycopeptides)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation enhances bioavailability and anti-inflammatory activity.", "mechanism": "Kaempferol glycosides reduce inflammatory responses via antioxidant and immunomodulatory effects.", "protein": "Kaempferol glycosides", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Oxidative stress-related diseases", "glycan_involvement": "Glycosylation improves solubility and cellular uptake.", "mechanism": "Quercetin glycosides act as antioxidants, reducing oxidative damage.", "protein": "Quercetin glycosides", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Immune dysfunction", "glycan_involvement": "Potential glycosylation may affect nucleotide-protein interactions.", "mechanism": "Nucleotides regulate immune function and support recovery during illness.", "protein": "Nucleotides (5\u2032-guanosine monophosphate, 5\u2032-uridine monophosphate)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycan moieties may influence metabolic effects.", "mechanism": "Theabrownins reduce body weight and triglycerides via lipid-lowering activity.", "protein": "Theabrownins", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "low", "disease": "Tumor (cancer)", "glycan_involvement": "Glycosylation enhances stability and bioactivity.", "mechanism": "Myricetin glycosides exhibit anti-tumor properties through antioxidant and cell signaling modulation.", "protein": "Myricetin glycosides", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation increases CNS bioavailability.", "mechanism": "Apigenin glycosides may provide neuroprotective effects via antioxidant and anti-inflammatory actions.", "protein": "Apigenin glycosides", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "low", "disease": "Gastrointestinal disorders", "glycan_involvement": "Triglycosylation enhances solubility and gut absorption.", "mechanism": "Chrysoeriol triglucoside may aid gastrointestinal recovery and function.", "protein": "Chrysoeriol triglucoside", "relationship_type": "protective", "source_pmcid": "PMC12385791" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation of MCT1 may affect its transport function.", "mechanism": "MPP reduces butyric acid production, affecting MCT1-mediated fatty acid transport and reducing lipid accumulation in adipocytes.", "protein": "Monocarboxylate transporter 1 (MCT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385833" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may regulate PPAR-\u03b3 activity and adipocyte differentiation.", "mechanism": "MPP\u2019s viscous fiber properties delay nutrient absorption and modulate PPAR-\u03b3-mediated adipogenesis.", "protein": "PPAR-\u03b3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12385833" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Akkermansia degrades mucin glycoproteins, influencing gut barrier and inflammation.", "mechanism": "MPP increases Akkermansia abundance, improving glucose tolerance, insulin sensitivity, and mucosal integrity.", "protein": "Akkermansia muciniphila", "protein_enriched": { "function": "", "gene_name": "SED5", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A7A0T2" }, "relationship_type": "protective", "source_pmcid": "PMC12385833" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Bacteroidota degrade dietary glycans, producing beneficial SCFAs.", "mechanism": "MPP increases Bacteroidota, which produce acetic and propionic acids, regulating immune balance and reducing obesity.", "protein": "Bacteroidota (phylum)", "relationship_type": "protective", "source_pmcid": "PMC12385833" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Bacillota metabolize dietary glycans to butyrate, linked to adiposity.", "mechanism": "High Bacillota/Bacteroidota ratio is associated with obesity; MPP reduces Bacillota abundance.", "protein": "Bacillota (phylum)", "relationship_type": "causal", "source_pmcid": "PMC12385833" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Parabacteroides secrete SCFAs from glycan metabolism, influencing host metabolism.", "mechanism": "MPP reduces Parabacteroides abundance, alleviating metabolic syndrome and inflammation.", "protein": "Parabacteroides", "relationship_type": "causal", "source_pmcid": "PMC12385833" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycan fermentation by Coproplasma increases butyrate, promoting adiposity.", "mechanism": "MPP reduces Coproplasma, a butyrate producer linked to obesity.", "protein": "Coproplasma", "relationship_type": "causal", "source_pmcid": "PMC12385833" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Acetatifactor metabolizes glycans, influencing inflammatory pathways.", "mechanism": "MPP reduces Acetatifactor, which is associated with inflammation and obesity.", "protein": "Acetatifactor", "relationship_type": "causal", "source_pmcid": "PMC12385833" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Phocaeicola metabolizes dietary glycans, affecting SCFA profiles.", "mechanism": "MPP reduces Phocaeicola, linked to carbohydrate metabolism and metabolic syndrome.", "protein": "Phocaeicola", "relationship_type": "causal", "source_pmcid": "PMC12385833" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Likely involved in glycan metabolism and SCFA production.", "mechanism": "MPP increases Nanosyncoccus, positively correlated with propionic acid and improved metabolic outcomes.", "protein": "Nanosyncoccus", "relationship_type": "protective", "source_pmcid": "PMC12385833" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Bacterial glycoproteins may mediate host-microbe interactions via glycan recognition.", "mechanism": "Increased abundance correlates with reduced obesity and improved metabolic health; produces acetate SCFA.", "protein": "Bifidobacterium glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoproteins may facilitate SCFA production and gut colonization.", "mechanism": "Elevated levels associated with increased SCFA production and reduced obesity.", "protein": "Lactobacillus glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoproteins may be involved in SCFA fermentation and host signaling.", "mechanism": "Higher abundance linked to reduced visceral fat and improved metabolic markers; produces acetic acid.", "protein": "Blautia glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoproteins may mediate butyrate synthesis and gut barrier effects.", "mechanism": "Increased abundance correlates with higher butyrate production and reduced weight gain.", "protein": "Lachnospiraceae_NK4A136_group glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycoproteins may facilitate SCFA metabolism.", "mechanism": "Associated with increased acetic acid production and improved metabolic outcomes.", "protein": "Clostridium-sensu-stricto-1 glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycoproteins may be involved in SCFA production.", "mechanism": "Positive correlation with valeric acid and butyrate, contributing to metabolic health.", "protein": "Faecalibaculum glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycoproteins may mediate SCFA synthesis and host interaction.", "mechanism": "Negative correlation with body weight and metabolic markers; produces multiple SCFAs.", "protein": "Alistipes glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycoproteins may be involved in SCFA metabolism.", "mechanism": "Positive correlation with SCFA production and metabolic improvement.", "protein": "Dubosiella glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoproteins may mediate pathogenicity and inflammation.", "mechanism": "Increased abundance associated with obesity and metabolic disorders; produces harmful metabolites.", "protein": "Fusobacteria glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycoproteins may facilitate host cell invasion and immune evasion.", "mechanism": "Elevated levels linked to gut dysbiosis and obesity; pathogenic effects.", "protein": "Escherichia-Shigella glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12385894" }, { "confidence": "high", "disease": "Osteogenesis imperfecta type XVI", "glycan_involvement": "CREB3L1 is glycosylated; glycosylation may affect protein folding and ER stress response.", "mechanism": "Loss-of-function mutations reduce CREB3L1-mediated transcription of COL1A1, impairing collagen synthesis and bone matrix formation.", "protein": "CREB3L1", "protein_enriched": { "function": "Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activat", "gene_name": "CREB3L2", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q70SY1" }, "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "medium", "disease": "Tooth agenesis", "glycan_involvement": "Glycosylation may modulate CREB3L1 stability and secretion in dental tissues.", "mechanism": "CREB3L1 mutations linked to hypodontia/oligodontia via impaired osteoblast and odontoblast function.", "protein": "CREB3L1", "protein_enriched": { "function": "Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activat", "gene_name": "CREB3L2", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q70SY1" }, "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "high", "disease": "Primary hypertrophic osteoarthropathy", "glycan_involvement": "SLCO2A1 glycosylation affects membrane localization and transporter activity.", "mechanism": "Mutations impair prostaglandin E2 transport/degradation, leading to bone inflammation and abnormal remodeling.", "protein": "SLCO2A1", "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "high", "disease": "Metaphyseal dysplasia Pyle type", "glycan_involvement": "SFRP4 is glycosylated; glycosylation may affect secretion and Wnt ligand binding.", "mechanism": "Loss-of-function mutation (P320T) reduces SFRP4 inhibition of Wnt signaling, causing abnormal bone formation and cortical thinning.", "protein": "SFRP4", "protein_enriched": { "function": "Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell ", "gene_name": "SFRP4", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G72747WU", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G06356OH", "G10486CT", "G18647XP", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G41071NU", "G42124LM", "G45395BF", "G47644PP", "G51640FO", "G65184UU", "G72291OX", "G72735IY", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G84452RH", "G90659AW", "G95177YH", "G95865ZB", "G34989PA", "G84225JN" ], "uniprot_id": "Q6FHJ7" }, "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "medium", "disease": "Tooth agenesis", "glycan_involvement": "Glycosylation may influence SFRP4 function in dental tissues.", "mechanism": "Reduced SFRP4 activity disrupts Wnt signaling in dental development, leading to partial tooth agenesis.", "protein": "SFRP4", "protein_enriched": { "function": "Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell ", "gene_name": "SFRP4", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G72747WU", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G06356OH", "G10486CT", "G18647XP", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G41071NU", "G42124LM", "G45395BF", "G47644PP", "G51640FO", "G65184UU", "G72291OX", "G72735IY", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G84452RH", "G90659AW", "G95177YH", "G95865ZB", "G34989PA", "G84225JN" ], "uniprot_id": "Q6FHJ7" }, "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "high", "disease": "Endosteal hyperostosis (osteosclerosis)", "glycan_involvement": "LRP5 glycosylation is critical for receptor folding and Wnt ligand interaction.", "mechanism": "Gain-of-function mutation (R638H) enhances Wnt/\u03b2-catenin signaling, increasing bone density and cortical thickening.", "protein": "LRP5", "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "medium", "disease": "Osteogenesis imperfecta type XVI", "glycan_involvement": "Glycosylation may modulate LRP5 receptor activity.", "mechanism": "LRP5 mutation may antagonize bone fragility by increasing bone density, mitigating OI phenotype.", "protein": "LRP5", "relationship_type": "protective", "source_pmcid": "PMC12386054" }, { "confidence": "high", "disease": "Osteoporosis/increased fracture risk", "glycan_involvement": "LRP6 glycosylation affects receptor trafficking and signaling.", "mechanism": "I1062V variant impairs Wnt/\u03b2-catenin signaling, reducing bone accrual and increasing fracture risk.", "protein": "LRP6", "protein_enriched": { "function": "Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (PubMed:11357136, PubMed:1144", "gene_name": "LRP6", "glycan_count": 4, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G81315DD", "G62765YT", "G09724ZC", "G22573RC" ], "uniprot_id": "O75581" }, "relationship_type": "causal", "source_pmcid": "PMC12386054" }, { "confidence": "medium", "disease": "Tooth agenesis", "glycan_involvement": "Glycosylation may affect LRP6 function in dental development.", "mechanism": "Missense variants in LRP6 (not I1062V) are associated with tooth agenesis via Wnt pathway disruption.", "protein": "LRP6", "protein_enriched": { "function": "Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (PubMed:11357136, PubMed:1144", "gene_name": "LRP6", "glycan_count": 4, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G81315DD", "G62765YT", "G09724ZC", "G22573RC" ], "uniprot_id": "O75581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386054" }, { "confidence": "low", "disease": "Osteoporosis/increased fracture risk", "glycan_involvement": "Glycosylation may regulate SFRP4 stability and activity.", "mechanism": "Reduced SFRP4 activity may increase Wnt signaling, potentially counteracting osteoporosis.", "protein": "SFRP4", "protein_enriched": { "function": "Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell ", "gene_name": "SFRP4", "glycan_count": 31, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G27058EU", "G72747WU", "G01650EU", "G02815KT", "G02886BB", "G06110VR", "G06356OH", "G10486CT", "G18647XP", "G23294PN", "G28541PG", "G37399XV", "G39446WN", "G41071NU", "G42124LM", "G45395BF", "G47644PP", "G51640FO", "G65184UU", "G72291OX", "G72735IY", "G72790NZ", "G80920RR", "G82463GQ", "G83460ZZ", "G84452RH", "G90659AW", "G95177YH", "G95865ZB", "G34989PA", "G84225JN" ], "uniprot_id": "Q6FHJ7" }, "relationship_type": "protective", "source_pmcid": "PMC12386054" }, { "confidence": "high", "disease": "Placental insufficiency", "glycan_involvement": "Glycosylation required for fusogenic activity", "mechanism": "Mediates trophoblast fusion for placental development", "protein": "Syncytin-1", "relationship_type": "causal/protective", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Immune tolerance failure (maternal-fetal)", "glycan_involvement": "Glycosylation modulates immunosuppressive function", "mechanism": "Immunosuppressive domain inhibits maternal immune rejection", "protein": "Syncytin-2", "relationship_type": "protective", "source_pmcid": "PMC12386078" }, { "confidence": "medium", "disease": "Osteoclast-related bone disorders", "glycan_involvement": "Glycosylation affects cell-cell fusion efficiency", "mechanism": "Promotes fusion of osteoclast precursors for bone remodeling", "protein": "Syncytin-1", "relationship_type": "causal", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Ovine pulmonary adenocarcinoma (OPA)", "glycan_involvement": "Glycosylation required for receptor binding and entry", "mechanism": "JSRV Env mediates infection and transformation of lung cells", "protein": "JSRV Env", "relationship_type": "causal", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Feline leukemia/lymphoma", "glycan_involvement": "Glycosylation modulates receptor usage and tropism", "mechanism": "Recombination with enFeLV Env increases pathogenicity (FeLV-B)", "protein": "FeLV Env", "relationship_type": "causal", "source_pmcid": "PMC12386078" }, { "confidence": "medium", "disease": "Koala chlamydial disease", "glycan_involvement": "Glycosylation affects Env-receptor interactions", "mechanism": "KoRV infection associated with increased susceptibility", "protein": "KoRV Env", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386078" }, { "confidence": "medium", "disease": "Koala tumorigenesis", "glycan_involvement": "Glycosylation required for viral entry and cell transformation", "mechanism": "KoRV integration and Env expression linked to tumor formation", "protein": "KoRV Env", "relationship_type": "causal", "source_pmcid": "PMC12386078" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "Glycosylation influences antigenicity and immune recognition", "mechanism": "HERV-K Env expression upregulated in HIV infection, modulates immune response", "protein": "HERV-K Env", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Porcine ERV zoonosis risk (xenotransplantation)", "glycan_involvement": "Glycosylation required for cross-species receptor binding", "mechanism": "PERV Env mediates infection of human cells via HuPAR2 receptor", "protein": "PERV Env", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Murine leukemia virus infection", "glycan_involvement": "Glycosylation modulates receptor binding affinity", "mechanism": "Fv-4 Env competitively blocks MLV receptor, preventing infection", "protein": "Fv-4 Env", "relationship_type": "protective", "source_pmcid": "PMC12386078" }, { "confidence": "high", "disease": "Chronic Lymphocytic Leukemia (CLL)", "glycan_involvement": "CD22 is a sialylated glycoprotein; glycosylation is essential for ligand binding and surface expression.", "mechanism": "Bryostatin 1 increases CD22 surface expression, sensitizing CLL cells to BL22 immunotoxin-induced apoptosis.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "high", "disease": "Diffuse Large B-cell Lymphoma (DLBCL)", "glycan_involvement": "Glycosylation modulates CD22 function and antibody recognition.", "mechanism": "Bryostatin 1 upregulates CD22, enhancing BL22-induced apoptosis in DLBCL cells.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Mantle Cell Lymphoma", "glycan_involvement": "Glycosylation required for CD22 surface expression.", "mechanism": "Bryostatin 1 increases CD22 expression, sensitizing cells to BL22.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Hairy Cell Leukemia (HCL)", "glycan_involvement": "CD11c is a glycoprotein; glycosylation affects cell adhesion and immune recognition.", "mechanism": "Bryostatin 1 induces differentiation of CLL cells toward HCL-like phenotype with increased CD11c expression.", "protein": "CD11c", "protein_enriched": { "function": "Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antige", "gene_name": "FCER2", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P06734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Bcl-2 is glycosylated; glycosylation may affect stability and degradation.", "mechanism": "Bryostatin 1 induces ubiquitination and proteasomal degradation of Bcl-2, promoting apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Chronic Lymphocytic Leukemia (CLL)", "glycan_involvement": "Bax glycosylation may regulate mitochondrial targeting.", "mechanism": "Bryostatin 1 increases Bax expression, shifting the Bcl-2/Bax ratio toward apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Chronic Lymphocytic Leukemia (CLL)", "glycan_involvement": "PKC\u03b2II is glycosylated; glycosylation may affect localization and function.", "mechanism": "Bryostatin 1 activates PKC\u03b2II, leading to downstream effects on apoptosis and differentiation.", "protein": "PKC\u03b2II", "protein_enriched": { "function": "", "gene_name": "PRKCB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05771-2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "low", "disease": "Chronic Lymphocytic Leukemia (CLL)", "glycan_involvement": "Mcl-1 glycosylation may regulate stability.", "mechanism": "Bryostatin 1 increases Mcl-1 expression, contributing to anti-apoptotic signaling.", "protein": "Mcl-1", "relationship_type": "biomarker", "source_pmcid": "PMC12386199" }, { "confidence": "medium", "disease": "Relapsed Lymphoma", "glycan_involvement": "CD5 is a glycoprotein; glycosylation affects immune signaling.", "mechanism": "Increase in CD5 cell apoptosis correlates with clinical response to bryostatin 1 and vincristine.", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC12386199" }, { "confidence": "low", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation may regulate mitochondrial release.", "mechanism": "Bryostatin 1 increases Smac/DIABLO release, promoting caspase-dependent apoptosis.", "protein": "Smac/DIABLO", "protein_enriched": { "function": "Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC", "gene_name": "DIABLO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NR28" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386199" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "CRP is upregulated by IL-6/JAK-STAT signaling in MASLD, reflecting systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates SAA solubility and aggregation.", "mechanism": "SAA is increased in MASLD due to hepatic acute-phase response, amplifying inflammation.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "ASCVD", "glycan_involvement": "VWF glycosylation regulates its multimerization and platelet binding.", "mechanism": "Elevated VWF in MASLD promotes hypercoagulability and thrombosis, increasing ASCVD risk.", "protein": "Von Willebrand factor (VWF)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "ASCVD", "glycan_involvement": "N-glycosylation affects fibrinogen's clotting function.", "mechanism": "High fibrinogen in MASLD enhances clot formation, contributing to cardiovascular events.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation is essential for GLP-1 receptor cell surface expression and ligand binding.", "mechanism": "GLP-1 agonists improve hepatic metabolism and reduce steatosis in MASLD.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386202" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "N-glycosylation modulates ICAM-1 adhesion properties.", "mechanism": "ICAM-1 upregulation in hepatic endothelium promotes leukocyte recruitment and inflammation in MASH.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12386202" }, { "confidence": "medium", "disease": "ASCVD", "glycan_involvement": "Glycosylation affects VCAM-1 binding to integrins.", "mechanism": "VCAM-1 mediates leukocyte adhesion to endothelium, driving vascular inflammation in MASLD/ASCVD.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "ASCVD", "glycan_involvement": "N-glycosylation influences ApoB secretion and LDL particle formation.", "mechanism": "Elevated ApoB-containing lipoproteins in MASLD promote atherogenesis and ASCVD.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation is required for adiponectin multimerization and bioactivity.", "mechanism": "Low adiponectin in MASLD reduces anti-inflammatory and insulin-sensitizing effects, worsening disease.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation affects leptin secretion and receptor interaction.", "mechanism": "Elevated leptin in MASLD/MASH drives hepatic inflammation and fibrosis.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12386202" }, { "confidence": "high", "disease": "Cancer Cachexia", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation affects stability and receptor binding.", "mechanism": "IL-6 activates gp130/STAT3 signaling, driving muscle atrophy and systemic inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Cancer Cachexia", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "gp130 is the receptor for IL-6; mediates STAT3 activation and muscle wasting.", "protein": "gp130", "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Cancer Cachexia", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates secretion and activity.", "mechanism": "TNF-\u03b1 activates NF-\u03baB, promoting muscle proteolysis and anorexia.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Muscle Wasting", "glycan_involvement": "Activin A is glycosylated; glycosylation affects receptor interaction.", "mechanism": "Activin A binds activin receptors, activates Smad signaling, induces muscle atrophy.", "protein": "Activin A", "protein_enriched": { "function": "Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythr", "gene_name": "INHBA", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G43417UB", "G70994MS" ], "uniprot_id": "P08476" }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Pancreatic Cancer", "glycan_involvement": "TWEAK is glycosylated; glycosylation influences receptor binding.", "mechanism": "Tumor-derived TWEAK binds Fn14, activates NF-\u03baB, upregulates MuRF1, drives cachexia.", "protein": "TWEAK", "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Muscle Wasting", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Fn14 mediates TWEAK signaling, leading to muscle proteolysis and ER stress.", "protein": "Fn14 (TWEAKR)", "protein_enriched": { "function": "Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selen", "gene_name": "SARS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP81" }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Cancer Cachexia", "glycan_involvement": "O-glycosylation modulates stability and receptor activation.", "mechanism": "Ghrelin stimulates appetite and inhibits muscle proteolysis via GHS-R1a.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "protective", "source_pmcid": "PMC12386252" }, { "confidence": "medium", "disease": "Ghrelin Resistance", "glycan_involvement": "LEAP2 is glycosylated; glycosylation may affect receptor antagonism.", "mechanism": "LEAP2 antagonizes GHS-R1a, contributing to ghrelin resistance in cachexia.", "protein": "LEAP2", "protein_enriched": { "function": "Has an antimicrobial activity", "gene_name": "LEAP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q969E1" }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "medium", "disease": "Gut Barrier Dysfunction", "glycan_involvement": "Claudin-2 is glycosylated; glycosylation affects tight junction integrity.", "mechanism": "IL-6 upregulates claudin-2, increasing intestinal permeability and systemic inflammation.", "protein": "Claudin-2", "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Bone Loss/Osteoporosis", "glycan_involvement": "RANKL is glycosylated; glycosylation modulates receptor binding and activity.", "mechanism": "RANKL promotes osteoclastogenesis, leading to bone resorption in cachexia.", "protein": "RANKL", "protein_enriched": { "function": "Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell prolif", "gene_name": "Tnfsf11", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "O35235" }, "relationship_type": "causal", "source_pmcid": "PMC12386252" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated AST reflects hepatic injury after perinatal hypoxia/acidosis.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation modulates ALT secretion and activity.", "mechanism": "ALT elevation indicates hepatocellular injury in neonates with acidosis.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "medium", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Glycosylation may influence AST release during injury.", "mechanism": "AST correlates with severity of HIE and perinatal insult.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "high", "disease": "Renal dysfunction", "glycan_involvement": "Not applicable.", "mechanism": "Elevated creatinine indicates impaired renal function after perinatal acidosis.", "protein": "Creatinine", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects GGT serum levels and activity.", "mechanism": "GGT is a marker of cholestatic or hepatocellular injury.", "protein": "GGT (Gamma-glutamyl transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "N-glycosylation critical for ALK-P stability and function.", "mechanism": "ALK-P elevation may indicate hepatic or bone involvement in neonates.", "protein": "ALK-P (Alkaline Phosphatase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "medium", "disease": "Renal dysfunction", "glycan_involvement": "Glycosylation may affect AST clearance in renal dysfunction.", "mechanism": "Concurrent elevation of AST and creatinine suggests multi-organ injury.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "low", "disease": "Respiratory distress", "glycan_involvement": "Glycosylation influences AST serum persistence.", "mechanism": "Elevated AST may reflect systemic hypoxic injury contributing to respiratory distress.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "low", "disease": "Hypoxic-ischemic encephalopathy (HIE)", "glycan_involvement": "Glycosylation modulates ALT serum levels.", "mechanism": "ALT elevation may parallel AST in reflecting hypoxic injury severity.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "low", "disease": "Renal dysfunction", "glycan_involvement": "Glycosylation affects GGT stability.", "mechanism": "GGT may be altered in multi-organ dysfunction after perinatal asphyxia.", "protein": "GGT (Gamma-glutamyl transferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12386278" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "SLC39A8 deficiency causes hypoglycosylation (CDG type II) due to impaired Mn2+ transport, impacting glycoprotein biosynthesis.", "mechanism": "Missense variant (rs13107325) alters metal ion transport (Mn2+, Zn2+), affecting immune/inflammatory responses in lung tissue.", "protein": "SLC39A8 (ZIP8)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Impaired glycosylation via Mn2+ deficiency; ZIP8 upregulation protects lung cells from apoptosis.", "mechanism": "Missense variant (rs13107325) may dysregulate metal ion homeostasis, increasing susceptibility to inflammation and COPD.", "protein": "SLC39A8 (ZIP8)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "high", "disease": "Type II Congenital Disorder of Glycosylation (CDG)", "glycan_involvement": "Directly causes defective N-glycosylation due to Mn2+ shortage for glycosyltransferases.", "mechanism": "Loss-of-function mutations cause Mn2+ deficiency, leading to multi-organ hypoglycosylation and severe metabolic symptoms.", "protein": "SLC39A8 (ZIP8)", "relationship_type": "causal", "source_pmcid": "PMC12386338" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Potential glycosylation may regulate protein stability/localization; not directly shown.", "mechanism": "Missense variant (rs2307111) may affect centriole function, cell division, and immune cell motility, linking obesity and asthma risk.", "protein": "POC5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386338" }, { "confidence": "medium", "disease": "COPD", "glycan_involvement": "Possible glycosylation involvement in centriole assembly; not directly demonstrated.", "mechanism": "Variant may contribute to metabolic dysregulation and inflammation, increasing COPD risk in obese individuals.", "protein": "POC5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386338" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates ENPP2 secretion and activity.", "mechanism": "Missense variant associated with fat-free mass and asthma risk; ENPP2 involved in lipid signaling and inflammation.", "protein": "ENPP2", "relationship_type": "biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation may affect SH2B1 stability and signaling.", "mechanism": "Missense variant linked to BMI and asthma; SH2B1 modulates cytokine signaling and metabolic pathways.", "protein": "SH2B1", "protein_enriched": { "function": "Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptor", "gene_name": "SH2B1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRF2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "low", "disease": "COPD", "glycan_involvement": "Glycosylation may regulate FAIM2 membrane localization.", "mechanism": "3\u2019UTR variant associated with BMI and COPD; FAIM2 inhibits apoptosis, may influence lung cell survival.", "protein": "FAIM2", "protein_enriched": { "function": "Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation", "gene_name": "FBXO28", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NVF7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Glycosylation may affect enzyme activity.", "mechanism": "Missense variant associated with alcohol intake and asthma risk; ADH1B affects alcohol metabolism and immune modulation.", "protein": "ADH1B", "protein_enriched": { "function": "Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitr", "gene_name": "ADH1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00325" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386338" }, { "confidence": "medium", "disease": "Scoliosis", "glycan_involvement": "Potential glycosylation may affect protein interactions in centrosome.", "mechanism": "POC5 mutation disrupts centriole function, linked to adolescent idiopathic scoliosis.", "protein": "POC5", "relationship_type": "causal", "source_pmcid": "PMC12386338" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "NUS1 is essential for N-glycosylation precursor synthesis.", "mechanism": "Upregulated in OSCC saliva; involved in dolichol biosynthesis and N-linked glycosylation, reflecting tumor-associated metabolic changes.", "protein": "NUS1", "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "RCN1 is an N-glycosylated ER protein; glycosylation may affect stability and secretion.", "mechanism": "Elevated in OSCC saliva; regulates ER calcium homeostasis and cell proliferation.", "protein": "RCN1", "protein_enriched": { "function": "May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment", "gene_name": "RCN1", "glycan_count": 96, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO", "G00273SJ", "G01485JJ", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06110VR", "G07755XJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G11314AS", "G11870QZ", "G14260UH", "G14972EH", "G14994KB", "G17208MA", "G18647XP", "G20528HD", "G22572EH", "G23719VF", "G24528MX", "G25451PN", "G25637MV", "G25987BV", "G27058EU", "G28681TP", "G29299MO", "G31852PQ", "G35029YA", "G36379GD", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46902YN", "G47644PP", "G49874UX", "G49955PK", "G50073PQ", "G50282JC", "G50757KG", "G51653BI", "G54010QB", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59924QI", "G60177UT", "G60834IK", "G62765YT", "G63381RX", "G64527OM", "G65019XG", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G74430RZ", "G76295SF", "G77547TA", "G80475RE", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G84349RE", "G84820NF", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87389XI", "G88725PI", "G88891KO", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92135MA", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G95865ZB" ], "uniprot_id": "Q15293" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "Predicted glycoprotein; glycosylation may influence protein function in ciliogenesis.", "mechanism": "Significantly upregulated in OSCC saliva and tissues; correlates with histological differentiation.", "protein": "CPLANE1", "protein_enriched": { "function": "Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier", "gene_name": "CGN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2M7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "high", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "CCL20 is O-glycosylated, which may modulate chemokine activity and secretion.", "mechanism": "Highly upregulated in OSCC saliva and advanced stages; correlates with Fusobacterium abundance, indicating a microbiome\u2013immune axis.", "protein": "CCL20", "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Potentially Malignant Disorders (OPMDs)", "glycan_involvement": "N-glycosylation pathway involvement.", "mechanism": "Intermediate upregulation in OPMDs, suggesting role in early carcinogenesis.", "protein": "NUS1", "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Potentially Malignant Disorders (OPMDs)", "glycan_involvement": "N-glycosylation of RCN1.", "mechanism": "Elevated in OPMDs, indicating early ER stress/glycoprotein changes.", "protein": "RCN1", "protein_enriched": { "function": "May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment", "gene_name": "RCN1", "glycan_count": 96, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G49108TO", "G00273SJ", "G01485JJ", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06110VR", "G07755XJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G11314AS", "G11870QZ", "G14260UH", "G14972EH", "G14994KB", "G17208MA", "G18647XP", "G20528HD", "G22572EH", "G23719VF", "G24528MX", "G25451PN", "G25637MV", "G25987BV", "G27058EU", "G28681TP", "G29299MO", "G31852PQ", "G35029YA", "G36379GD", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46902YN", "G47644PP", "G49874UX", "G49955PK", "G50073PQ", "G50282JC", "G50757KG", "G51653BI", "G54010QB", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59924QI", "G60177UT", "G60834IK", "G62765YT", "G63381RX", "G64527OM", "G65019XG", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G73968GN", "G74430RZ", "G76295SF", "G77547TA", "G80475RE", "G80920RR", "G83229XP", "G83460ZZ", "G83633GK", "G84349RE", "G84820NF", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87389XI", "G88725PI", "G88891KO", "G90575OW", "G90659AW", "G90734RJ", "G92050GC", "G92135MA", "G92275SC", "G92406TI", "G94854LT", "G95177YH", "G95865ZB" ], "uniprot_id": "Q15293" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Potentially Malignant Disorders (OPMDs)", "glycan_involvement": "Predicted glycoprotein.", "mechanism": "Increased expression in OPMDs, marking early malignant transformation.", "protein": "CPLANE1", "protein_enriched": { "function": "Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier", "gene_name": "CGN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P2M7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Potentially Malignant Disorders (OPMDs)", "glycan_involvement": "O-glycosylation modulates chemokine function.", "mechanism": "Upregulated in OPMDs, especially with Fusobacterium enrichment.", "protein": "CCL20", "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "low", "disease": "Leukoplakia", "glycan_involvement": "N-glycosylation precursor synthesis.", "mechanism": "Elevated in leukoplakia, indicating early glycosylation pathway activation.", "protein": "NUS1", "relationship_type": "biomarker", "source_pmcid": "PMC12386369" }, { "confidence": "medium", "disease": "Oral Squamous Cell Carcinoma (OSCC)", "glycan_involvement": "O-glycosylation may regulate CCL20's immune signaling.", "mechanism": "CCL20 upregulation (linked to Fusobacterium) may promote tumor-promoting inflammation and immune modulation.", "protein": "CCL20", "relationship_type": "causal", "source_pmcid": "PMC12386369" }, { "confidence": "high", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Possible involvement of glycosylation in receptor function/desensitization (not directly measured).", "mechanism": "Upregulation of \u03b22AR in MetS hearts alters \u03b2-adrenergic signaling, increasing susceptibility to arrhythmia.", "protein": "\u03b22-adrenergic receptor (\u03b22AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "Adrb2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P10608" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "high", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Glycosylation may affect G protein localization/function (not directly measured).", "mechanism": "Increased G\u03b1i expression in MetS hearts shifts \u03b22AR signaling toward inhibitory pathways, contributing to cardiac dysfunction.", "protein": "G\u03b1i protein", "protein_enriched": { "function": "Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:18434541, PubMed:33762731, PubMed:3423", "gene_name": "GNAI1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P63096" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "high", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Glycosylation may modulate G\u03b1s stability/function (not directly measured).", "mechanism": "Decreased G\u03b1s protein levels in MetS hearts reduce stimulatory \u03b2-adrenergic signaling, impairing cardiac output.", "protein": "G\u03b1s protein", "protein_enriched": { "function": "Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:12391161, PubMed:17110384, PubMed:2148", "gene_name": "GNAS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P63092" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "medium", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "Glycosylation may affect \u03b2-arrestin recruitment (not directly measured).", "mechanism": "Reduced \u03b2-arrestin 1 in MetS hearts impairs \u03b22AR desensitization, increasing arrhythmia risk.", "protein": "\u03b2-arrestin 1", "protein_enriched": { "function": "Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-a", "gene_name": "ARRB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49407" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "high", "disease": "Lethal Arrhythmia", "glycan_involvement": "Glycosylation may regulate \u03b22AR trafficking and function (not directly measured).", "mechanism": "Elevated \u03b22AR expression and altered signaling in MetS hearts predispose to lethal arrhythmia upon adrenergic stimulation.", "protein": "\u03b22-adrenergic receptor (\u03b22AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "Adrb2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P10608" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "high", "disease": "Lethal Arrhythmia", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Abnormal phosphorylation of RyR2 in MetS increases diastolic Ca2+ leak, promoting arrhythmia.", "protein": "Ryanodine receptor 2 (RyR2)", "protein_enriched": { "function": "Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. ", "gene_name": "RYR2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G90039BC" ], "uniprot_id": "Q92736" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Potential role for glycosylation in receptor function (not directly measured).", "mechanism": "\u03b21AR levels unchanged in MetS, but altered \u03b2AR signaling is implicated in heart failure risk.", "protein": "\u03b21-adrenergic receptor (\u03b21AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equa", "gene_name": "ADRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P07700" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386379" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may affect receptor desensitization and signaling.", "mechanism": "\u03b22AR upregulation is associated with heart failure and altered cardiac response.", "protein": "\u03b22-adrenergic receptor (\u03b22AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "Adrb2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P10608" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386379" }, { "confidence": "medium", "disease": "Insulin Resistance", "glycan_involvement": "Glycosylation may modulate \u03b22AR signaling in metabolic disease.", "mechanism": "\u03b22AR function is modified in insulin resistance, contributing to cardiac dysfunction.", "protein": "\u03b22-adrenergic receptor (\u03b22AR)", "protein_enriched": { "function": "Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-", "gene_name": "Adrb2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P10608" }, "relationship_type": "causal", "source_pmcid": "PMC12386379" }, { "confidence": "low", "disease": "Metabolic Syndrome (MetS)", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "GRK2 mediates \u03b2AR phosphorylation/desensitization; levels unchanged in MetS but functionally relevant.", "protein": "GRK2", "relationship_type": "biomarker", "source_pmcid": "PMC12386379" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "INSR is a heavily N-glycosylated receptor; glycosylation is essential for its cell surface expression and function.", "mechanism": "Upregulation of INSR expression by geniposide enhances insulin signaling, improving insulin sensitivity.", "protein": "Insulin receptor (INSR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386427" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "N-glycosylation critical for INSR function in hepatocytes.", "mechanism": "Activation of INSR by geniposide improves hepatic insulin signaling, reducing steatosis and fibrosis.", "protein": "Insulin receptor (INSR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "IRS-2 is glycosylated; glycosylation may affect stability and signaling.", "mechanism": "Geniposide upregulates IRS-2, enhancing downstream insulin signaling and glucose metabolism.", "protein": "Insulin receptor substrate 2 (IRS-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "JAK2 is glycosylated; glycosylation may regulate its activity.", "mechanism": "Overactivation of JAK2 impairs insulin signaling and promotes inflammation; geniposide suppresses JAK2 expression.", "protein": "Janus kinase 2 (JAK2)", "relationship_type": "causal", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "AKT1 is O-glycosylated; glycosylation may modulate its activity.", "mechanism": "Geniposide increases AKT1 expression, promoting glucose uptake and glycogen synthesis.", "protein": "Protein kinase B (AKT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386427" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation affects secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes inflammation and disrupts insulin signaling; geniposide suppresses TNF-\u03b1 expression.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386427" }, { "confidence": "high", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "IL-6 is N-glycosylated; glycosylation is required for secretion and activity.", "mechanism": "IL-6 drives hepatic inflammation and fibrosis; geniposide reduces IL-6 expression.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "F4/80 is a glycoprotein; glycosylation is important for cell surface localization.", "mechanism": "F4/80 marks macrophage infiltration in liver; geniposide reduces F4/80 expression, indicating reduced inflammation.", "protein": "F4/80 (EMR1)", "protein_enriched": { "function": "Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development", "gene_name": "Adgre1", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q61549" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Non-alcoholic steatohepatitis (NASH)", "glycan_involvement": "AMPK is glycosylated; glycosylation may affect its stability.", "mechanism": "Geniposide increases AMPK expression, improving lipid and glucose metabolism, reducing steatosis.", "protein": "Adenosine monophosphate-activated protein kinase (AMPK)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386427" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "IGF1R is highly N-glycosylated; glycosylation is essential for receptor function.", "mechanism": "Altered IGF1R expression is associated with insulin resistance; geniposide modulates IGF1R expression.", "protein": "Insulin-like growth factor 1 receptor (IGF1R)", "relationship_type": "biomarker", "source_pmcid": "PMC12386427" }, { "confidence": "high", "disease": "Kidney transplant rejection", "glycan_involvement": "Tacrolimus formulation (Envarsus) uses glycoprotein drug delivery for improved bioavailability.", "mechanism": "Inhibits calcineurin, suppressing T-cell activation to prevent rejection.", "protein": "Tacrolimus (FK506-binding protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386444" }, { "confidence": "high", "disease": "Kidney transplant rejection", "glycan_involvement": "IgG glycosylation affects antibody effector function.", "mechanism": "Depletes T-cells via antibody-mediated cytotoxicity, reducing rejection risk.", "protein": "Thymoglobulin (anti-thymocyte globulin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Tacrolimus toxicity", "glycan_involvement": "Glycosylation modulates transporter activity and drug efflux.", "mechanism": "Limits tacrolimus absorption in enterocytes, affecting drug levels and toxicity risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "high", "disease": "Nephrotoxicity", "glycan_involvement": "Drug formulation as glycoprotein affects pharmacokinetics.", "mechanism": "High tacrolimus exposure causes acute kidney injury via vasoconstriction and tubular toxicity.", "protein": "Tacrolimus (FK506-binding protein)", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Neurotoxicity", "glycan_involvement": "Drug delivery system impacts CNS exposure.", "mechanism": "Supratherapeutic tacrolimus levels can cause neurological symptoms.", "protein": "Tacrolimus (FK506-binding protein)", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Cytomegalovirus infection", "glycan_involvement": "Viral envelope glycosylation critical for infectivity.", "mechanism": "CMV glycoproteins mediate viral entry and immune evasion in immunosuppressed patients.", "protein": "Cytomegalovirus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "BK virus infection", "glycan_involvement": "Glycosylation required for viral tropism.", "mechanism": "BK virus glycoproteins facilitate infection in immunosuppressed transplant recipients.", "protein": "BK virus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Tacrolimus toxicity", "glycan_involvement": "Glycosylation may affect enzyme stability and activity.", "mechanism": "Genetic variants affect tacrolimus metabolism, influencing toxicity risk.", "protein": "CYP3A5", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Kidney transplant rejection", "glycan_involvement": "IgG glycosylation modulates antibody-mediated rejection.", "mechanism": "High PRA indicates sensitization and increased rejection risk.", "protein": "Panel-reactive antibodies (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12386444" }, { "confidence": "medium", "disease": "Delayed graft function", "glycan_involvement": "Formulation glycosylation impacts drug release kinetics.", "mechanism": "Early supratherapeutic tacrolimus exposure may contribute to delayed graft function.", "protein": "Tacrolimus (FK506-binding protein)", "relationship_type": "causal", "source_pmcid": "PMC12386444" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described for Nrf2 in this context.", "mechanism": "Nrf2 activation increases antioxidant enzymes (GSH, SOD, HO-1), suppresses lipogenesis, and reduces inflammation and apoptosis in NAFLD.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described for Keap1 in this context.", "mechanism": "Keap1 upregulation leads to Nrf2 degradation, reducing antioxidant defense and promoting NAFLD progression.", "protein": "Keap1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "SREBP1 is known to be glycosylated, which may affect its stability and activity, but not directly discussed here.", "mechanism": "SREBP1 upregulation increases hepatic fatty acid and triglyceride synthesis, driving steatosis.", "protein": "SREBP1", "protein_enriched": { "function": "Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the im", "gene_name": "Kpna3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX" ], "uniprot_id": "O35344" }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "FAS is a glycoprotein; glycosylation may affect its enzymatic activity, but not directly discussed here.", "mechanism": "FAS upregulation promotes fatty acid synthesis, contributing to hepatic lipid accumulation.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Possible glycosylation, but not discussed in this article.", "mechanism": "ACC-1 upregulation increases fatty acid synthesis, exacerbating steatosis.", "protein": "ACC-1", "protein_enriched": { "function": "Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribos", "gene_name": "Eif3c", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8R1B4" }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "PPAR\u03b1 activation enhances mitochondrial fatty acid oxidation, counteracting steatosis.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Bcl-2 upregulation inhibits hepatic apoptosis, protecting against liver injury.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Bax upregulation promotes hepatic apoptosis, contributing to liver injury.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "Caspase-3 activation mediates apoptosis in hepatocytes, worsening liver injury.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "No direct glycosylation mechanism described.", "mechanism": "NF-\u03baB activation increases inflammatory cytokine production (TNF-\u03b1, IL-6), promoting hepatic inflammation and injury.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC12386455" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Inhibits insulin-dependent glucose transport and suppresses mitochondriogenesis and fatty acid synthesis, promoting insulin resistance.", "protein": "Fetuin A (FETUA)", "protein_enriched": { "function": "Probably involved in differentiation", "gene_name": "Ahsg", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G92359CR", "G15488CF", "G39397SW", "G49108TO" ], "uniprot_id": "P29699" }, "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Recruits M1-type macrophages and transforms M2 to M1, triggering inflammation.", "protein": "Fetuin A (FETUA)", "protein_enriched": { "function": "Probably involved in differentiation", "gene_name": "Ahsg", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G92359CR", "G15488CF", "G39397SW", "G49108TO" ], "uniprot_id": "P29699" }, "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Essential for N-glycosylation of nascent proteins.", "mechanism": "Interacts with misfolded glycoproteins, delays transport, and is upregulated in obesity-linked ECM remodeling.", "protein": "Ribophorin I (RPN1)", "protein_enriched": { "function": "Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The resp", "gene_name": "Cyc1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9D0M3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Fibrosis/ECM remodeling", "glycan_involvement": "Glycosylation affects chaperone activity.", "mechanism": "Prevents collagen fibril aggregation, its downregulation leads to ECM stiffness and fibrosis.", "protein": "Serpin H1 (SERPH1)", "protein_enriched": { "function": "Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4 (By similarity). May play a role in inflammation", "gene_name": "Lxn", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P70202" }, "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Fibrosis/ECM remodeling", "glycan_involvement": "Keratan sulfate glycosylation critical for ECM function.", "mechanism": "Enhances collagen hydrogel resistance, upregulated in ECM remodeling during obesity.", "protein": "Lumican (LUM)", "relationship_type": "biomarker", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation modulates stability and ECM interaction.", "mechanism": "Protects fibronectin from mechanical stress-induced conformational changes in hypertrophied adipocytes.", "protein": "Albumin (ALB)", "relationship_type": "protective", "source_pmcid": "PMC12386456" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation influences extracellular release and immune activation.", "mechanism": "Acts as a damage-associated molecular pattern, activates macrophages, and promotes cytokine secretion.", "protein": "High Mobility Group Box 1 (HMGB1)", "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for cell surface localization and activity.", "mechanism": "Generates H2O2, stimulates insulin receptor substrate phosphorylation, mimics insulin effects, and inhibits lipolysis.", "protein": "AOC3", "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Fibrosis/ECM remodeling", "glycan_involvement": "Glycosylation modulates enzymatic activity.", "mechanism": "Catalyzes cross-linking in fibronectin, leading to collagen deposition and impaired adipogenesis.", "protein": "Factor XIII-A (F13A)", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in", "gene_name": "Fgb", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G24748EV", "G86226EA", "G49108TO" ], "uniprot_id": "Q8K0E8" }, "relationship_type": "causal", "source_pmcid": "PMC12386456" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation essential for secretion and immune function.", "mechanism": "Produced by B1 lymphocytes, restrains inflammatory processes in adipose tissue.", "protein": "Immunoglobulin M heavy chain (IgM)", "relationship_type": "protective", "source_pmcid": "PMC12386456" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "N-glycosylation affects albumin stability and half-life.", "mechanism": "Albumin levels decrease in liver dysfunction; exercise transiently increases albumin via plasma volume shifts.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "high", "disease": "Inflammatory conditions", "glycan_involvement": "N-glycosylation modulates CRP's immune interactions.", "mechanism": "CRP rises in inflammation; exercise did not significantly alter CRP after hemoconcentration correction.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation required for ALP activity and secretion.", "mechanism": "ALP reflects bone turnover; exercise transiently increases ALP activity.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "N-glycosylation essential for GGT function.", "mechanism": "GGT is elevated in liver dysfunction; exercise transiently increases GGT, confounding diagnosis.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation affects transferrin receptor binding.", "mechanism": "Transferrin levels reflect iron status; exercise may alter iron and transferrin concentrations.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Acute phase response", "glycan_involvement": "N-glycosylation modulates immunoglobulin effector functions.", "mechanism": "Immunoglobulin levels can change in response to inflammation and exercise.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Hemolytic anemia", "glycan_involvement": "N-glycosylation affects haptoglobin clearance.", "mechanism": "Haptoglobin binds free hemoglobin; levels decrease in hemolysis, which can occur after intense exercise.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "N-glycosylation modulates AGP's anti-inflammatory properties.", "mechanism": "AGP rises in inflammation; exercise may transiently affect AGP levels.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "low", "disease": "Metabolic syndrome", "glycan_involvement": "N-glycosylation required for ceruloplasmin stability.", "mechanism": "Ceruloplasmin is altered in metabolic syndrome; exercise may impact copper metabolism.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386491" }, { "confidence": "low", "disease": "Exercise-induced muscle damage", "glycan_involvement": "N-glycosylation essential for erythropoietin receptor binding.", "mechanism": "Erythropoietin supports RBC production after exercise-induced hemolysis.", "protein": "Erythropoietin", "relationship_type": "protective", "source_pmcid": "PMC12386491" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "No direct glycosylation; PTMs (citrullination/carbamylation) modulate antigenicity.", "mechanism": "Acts as autoantigen, promotes immune activation and inflammation.", "protein": "LL-37 (hCAP18)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386566" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "No direct glycosylation; PTMs critical.", "mechanism": "Acts as autoantigen; PTMs (cit-LL37, carb-LL37) enhance antigen presentation and autoantibody production.", "protein": "LL-37 (hCAP18)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Cancer (colon, breast, ovarian, lung)", "glycan_involvement": "No direct glycosylation; analogs may be glycosylated for improved function.", "mechanism": "Induces apoptosis and inhibits proliferation in cancer cells; analogs enhance selectivity.", "protein": "LL-37 (hCAP18)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12386566" }, { "confidence": "high", "disease": "Drug-resistant bacterial infections", "glycan_involvement": "SLP-51: Arg glycosylation improves stability and reduces hemolysis.", "mechanism": "Direct antimicrobial activity; analogs (OP-145, SAAP-148, SLP-51) show enhanced efficacy and reduced toxicity.", "protein": "LL-37 (hCAP18)", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Ulcerative colitis", "glycan_involvement": "No direct glycosylation; PTMs may modulate activity.", "mechanism": "Elevated LL-37 levels contribute to host cell damage and apoptosis at inflammation sites.", "protein": "LL-37 (hCAP18)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Rosacea", "glycan_involvement": "No direct glycosylation.", "mechanism": "High LL-37 levels linked to inflammation and tissue damage.", "protein": "LL-37 (hCAP18)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Chronic periodontitis", "glycan_involvement": "No direct glycosylation.", "mechanism": "Elevated LL-37 may contribute to tissue damage.", "protein": "LL-37 (hCAP18)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Cancer (breast)", "glycan_involvement": "No direct glycosylation.", "mechanism": "Induces apoptosis in breast cancer cells.", "protein": "KR-12", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12386566" }, { "confidence": "medium", "disease": "Cancer (colon)", "glycan_involvement": "No direct glycosylation.", "mechanism": "Inhibits proliferation and induces apoptosis in colon cancer cells.", "protein": "FF/CAP18", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12386566" }, { "confidence": "high", "disease": "Drug-resistant bacterial infections (MRSA, K. pneumoniae)", "glycan_involvement": "Arg N-glycosylation at C-terminus improves stability and reduces toxicity.", "mechanism": "Double-stapled, Arg-glycosylated analog with enhanced antimicrobial and antibiofilm activity, reduced hemolysis.", "protein": "SLP-51", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12386566" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "PI3K is a glycoprotein; glycosylation may affect stability and signaling.", "mechanism": "PI3K downregulation by DOX leads to impaired antioxidant signaling; SYA restores PI3K activity, reducing liver injury.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "Akt is glycosylated; glycosylation may modulate its activation.", "mechanism": "Akt phosphorylation is reduced by DOX, impairing cell survival; SYA upregulates Akt, promoting hepatoprotection.", "protein": "Akt", "protein_enriched": { "function": "AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, gro", "gene_name": "Akt1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47196" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "Nrf-2 activity may be modulated by glycoprotein interactions.", "mechanism": "Nrf-2 downregulation by DOX reduces antioxidant response; SYA upregulates Nrf-2, enhancing antioxidant defenses.", "protein": "Nrf-2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "O54968" }, "relationship_type": "protective", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "HO-1 is glycoprotein-associated; glycosylation may affect its stability.", "mechanism": "HO-1 expression is decreased by DOX, reducing cytoprotection; SYA restores HO-1, mitigating oxidative damage.", "protein": "HO-1", "protein_enriched": { "function": "Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous ", "gene_name": "Hmox1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06762" }, "relationship_type": "protective", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "GGT is a glycoprotein; glycosylation is essential for its activity.", "mechanism": "GGT is elevated in DOX-induced liver injury; SYA reduces GGT toward normal.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Doxorubicin-induced hepatotoxicity", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its secretion and function.", "mechanism": "ALP is increased in DOX-induced liver injury; SYA reduces ALP levels.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation is required for secretion.", "mechanism": "IL-6 is elevated in DOX-induced hepatic inflammation; SYA reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "IL-1\u03b2 is a glycoprotein; glycosylation is important for maturation.", "mechanism": "IL-1\u03b2 is increased in DOX-induced hepatic inflammation; SYA reduces IL-1\u03b2.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "Hepatic inflammation", "glycan_involvement": "TNF-\u03b1 is a glycoprotein; glycosylation affects secretion.", "mechanism": "TNF-\u03b1 is elevated in DOX-induced hepatic inflammation; SYA reduces TNF-\u03b1.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386595" }, { "confidence": "medium", "disease": "Hepatic inflammation", "glycan_involvement": "NF-\u03baB activity may be modulated by glycoprotein interactions.", "mechanism": "NF-\u03baB activation mediates inflammatory response in DOX-induced liver injury; SYA inhibits NF-\u03baB activation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386595" }, { "confidence": "high", "disease": "MODS", "glycan_involvement": "N-glycosylation required for secretion and stability; glycosylation may affect biomarker performance.", "mechanism": "NGAL is consistently upregulated in lung, kidney, and liver after trauma, correlating with MODS severity and activity.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12386635" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "N-glycosylation critical for renal secretion and function.", "mechanism": "NGAL is an early marker of kidney injury and may play a protective role in recovery post-ischemia/reperfusion.", "protein": "NGAL", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386635" }, { "confidence": "high", "disease": "Trauma-induced remote organ injury", "glycan_involvement": "N-glycosylation facilitates systemic distribution.", "mechanism": "NGAL upregulation reflects and mediates systemic inflammation and tissue damage in distant organs post-trauma.", "protein": "NGAL", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386635" }, { "confidence": "high", "disease": "SIRS", "glycan_involvement": "N-glycosylation affects immune recognition and clearance.", "mechanism": "NGAL promotes and reflects pro-inflammatory responses in SIRS after trauma.", "protein": "NGAL", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "N-glycosylation required for hepatic secretion.", "mechanism": "NGAL expression in liver correlates with tissue damage severity post-trauma.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Lung injury", "glycan_involvement": "N-glycosylation impacts pulmonary secretion and function.", "mechanism": "NGAL upregulation in lung tissue is associated with trauma-induced inflammation and injury.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation may affect CNS penetration and activity.", "mechanism": "NGAL contributes to neuroinflammation; inhibition (e.g., by berberine) reduces inflammation.", "protein": "NGAL", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Ischemia/Reperfusion Injury", "glycan_involvement": "N-glycosylation required for reparative function.", "mechanism": "NGAL is upregulated after IRI and may promote cell regeneration and repair.", "protein": "NGAL", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "N-glycosylation required for CRP function.", "mechanism": "CRP is upregulated in liver after trauma, indicating acute-phase response.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386635" }, { "confidence": "medium", "disease": "Fibrosis", "glycan_involvement": "Glycosylation affects TIMP1 stability and activity.", "mechanism": "TIMP1 upregulation in kidney and liver after trauma may contribute to tissue remodeling and fibrosis.", "protein": "TIMP1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386635" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "PON is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Reduced PON activity correlates with increased dyslipidemia and oxidative stress; BLE+POL increases PON activity.", "protein": "Paraoxonase (PON)", "relationship_type": "biomarker", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Fatty liver disease", "glycan_involvement": "IL-6 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Elevated IL-6 in liver indicates inflammation and fatty liver; BLE+POL reduces IL-6.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Premature aging", "glycan_involvement": "AGEs are non-enzymatic glycation adducts on proteins.", "mechanism": "AGEs accumulate with high galactose, driving aging and organ dysfunction; BLE+POL reduces AGE formation.", "protein": "Advanced glycation end products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Apoptosis (brain)", "glycan_involvement": "4-HNE modifies glycoproteins, impairing function.", "mechanism": "4-HNE accumulation induces neuronal apoptosis; BLE+POL reduces 4-HNE in brain.", "protein": "4-Hydroxynonenal (4-HNE)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Fatty liver disease", "glycan_involvement": "AST is glycosylated, influencing serum stability.", "mechanism": "Elevated AST signals liver damage; BLE+POL lowers AST.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Fatty liver disease", "glycan_involvement": "ALT glycosylation affects secretion.", "mechanism": "ALT elevation marks hepatic injury; BLE+POL reduces ALT.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386686" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "apoA-I glycosylation modulates HDL function.", "mechanism": "POL upregulates apoA-I, improving HDL-C and lipid profile.", "protein": "Apolipoprotein A-I (apoA-I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386686" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "CETP glycosylation affects activity and plasma half-life.", "mechanism": "POL inhibits CETP, reducing cholesterol transfer and improving lipid profile.", "protein": "Cholesteryl ester transfer protein (CETP)", "protein_enriched": { "function": "Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL t", "gene_name": "CETP", "glycan_count": 15, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G27058EU", "G45395BF", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G90659AW", "G43417UB", "G00912UN", "G10486CT", "G14796IU", "G59626AS", "G86795LJ" ], "uniprot_id": "P11597" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386686" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "\u03b1-Amylase glycosylation affects enzyme activity.", "mechanism": "BLE inhibits \u03b1-amylase, reducing postprandial glucose spikes.", "protein": "\u03b1-Amylase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386686" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "\u03b1-Glucosidase glycosylation modulates substrate specificity.", "mechanism": "BLE inhibits \u03b1-glucosidase, lowering glucose absorption.", "protein": "\u03b1-Glucosidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386686" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates SPARC secretion and ECM interactions.", "mechanism": "SPARC is upregulated in activated hepatic stellate cells, promoting ECM deposition.", "protein": "SPARC", "relationship_type": "biomarker", "source_pmcid": "PMC12386721" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects fibronectin's matrix assembly and cell adhesion.", "mechanism": "Fibronectin accumulation drives fibrotic matrix formation by activated HSCs.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12386721" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen glycosylation influences fibril formation and stability.", "mechanism": "Excess collagen I synthesis by HSCs is central to fibrotic scarring.", "protein": "Collagen type I", "protein_enriched": { "function": "Type I collagen is a member of group I collagen (fibrillar forming collagen)", "gene_name": "COL1A1", "glycan_count": 21, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G43417UB", "G57321FI", "G02815KT", "G05049YU", "G05724UK", "G06110VR", "G15664MX", "G25079LO", "G25637MV", "G31852PQ", "G39188ZX", "G41247ZX", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G72747WU", "G80920RR", "G85282JO", "G90659AW", "G49108TO" ], "uniprot_id": "P02452" }, "relationship_type": "causal", "source_pmcid": "PMC12386721" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates TIMP1 stability and activity.", "mechanism": "TIMP1 inhibits matrix metalloproteinases, reducing ECM degradation and promoting fibrosis.", "protein": "TIMP1", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386721" }, { "confidence": "medium", "disease": "Extracellular matrix remodeling disorders", "glycan_involvement": "Glycosaminoglycan chains are essential for decorin's ECM interactions.", "mechanism": "Decorin modulates collagen fibrillogenesis and limits excessive matrix deposition.", "protein": "Decorin", "relationship_type": "protective", "source_pmcid": "PMC12386721" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects CCN2 secretion and receptor binding.", "mechanism": "CCN2/CTGF promotes HSC activation and collagen synthesis.", "protein": "CCN2/CTGF", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12386721" }, { "confidence": "medium", "disease": "Cholangiopathies", "glycan_involvement": "O-glycosylation modulates keratin filament assembly.", "mechanism": "KRT19 is a marker of cholangiocyte activation and progenitor cell expansion in liver disease.", "protein": "Keratin 19", "relationship_type": "biomarker", "source_pmcid": "PMC12386721" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Limited direct glycosylation; indirect effects via ECM interactions.", "mechanism": "\u03b1-SMA marks myofibroblastic activation of HSCs, correlating with fibrogenesis.", "protein": "ACTA2", "relationship_type": "biomarker", "source_pmcid": "PMC12386721" }, { "confidence": "medium", "disease": "Stellate cell activation syndrome", "glycan_involvement": "Glycosylation may affect filament stability.", "mechanism": "GFAP expression indicates quiescent/early-activated HSCs; loss marks activation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386721" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "Glycosylation may modulate vinculin's cell adhesion properties.", "mechanism": "Vinculin upregulation reflects cytoskeletal remodeling in activated HSCs during injury.", "protein": "Vinculin", "protein_enriched": { "function": "Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex.", "gene_name": "VCL", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G83460ZZ", "G49108TO" ], "uniprot_id": "P18206" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386721" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "N-glycosylation required for proper folding and cell surface localization.", "mechanism": "ROCK inhibition upregulates E-cadherin, stabilizing melanocyte adhesion and residency, counteracting IFN-\u03b3-induced detachment.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "protective", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "N-glycosylation modulates receptor function and cell adhesion.", "mechanism": "ROCK inhibition increases DDR1, supporting melanocyte-keratinocyte interactions and dendrite maintenance.", "protein": "DDR1", "relationship_type": "protective", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Heavily glycosylated; glycosylation affects stability and signaling.", "mechanism": "Upregulated by ROCK inhibition and MITF, GPNMB promotes dendritic integrity and melanocyte survival.", "protein": "GPNMB", "relationship_type": "protective", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Glycosylation influences secretion and receptor binding.", "mechanism": "IFN-\u03b3 suppresses bFGF, leading to melanocyte apoptosis; ROCK inhibition restores bFGF, supporting survival.", "protein": "bFGF (FGF2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Vitiligo", "glycan_involvement": "Glycosylation required for stability and activity.", "mechanism": "IFN-\u03b3 suppresses ET-1, reducing melanocyte trophic support; ROCK inhibition partially restores ET-1.", "protein": "ET-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386722" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Glycosylation modulates chemokine gradient and receptor interaction.", "mechanism": "IFN-\u03b3 induces CXCL9, recruiting CXCR3+ CD8+ T cells, driving melanocyte destruction.", "protein": "CXCL9", "protein_enriched": { "function": "Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3", "gene_name": "CXCL9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q07325" }, "relationship_type": "causal", "source_pmcid": "PMC12386722" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Glycosylation affects chemokine stability and function.", "mechanism": "IFN-\u03b3 induces CXCL10, promoting immune cell infiltration and melanocyte apoptosis.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "causal", "source_pmcid": "PMC12386722" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "CXCR3+ CD8+ T cells are recruited by CXCL9/10, mediating melanocyte killing.", "protein": "CXCR3", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling p", "gene_name": "CXCR3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P49682" }, "relationship_type": "causal", "source_pmcid": "PMC12386722" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "SCF supports melanocyte proliferation and survival; expression is variably affected by ROCK inhibition.", "protein": "SCF", "relationship_type": "protective", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Depigmentation", "glycan_involvement": "N-glycosylation loss impairs adhesion.", "mechanism": "Loss of E-cadherin correlates with melanocyte detachment and depigmentation.", "protein": "E-cadherin", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the ", "gene_name": "CDH1", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G57321FI", "G49108TO" ], "uniprot_id": "P12830" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386722" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "Non-enzymatic glycation of proteins; altered glycan structures promote dysfunction.", "mechanism": "AGEs accumulate in muscle and impair function via oxidative stress and inflammation.", "protein": "Advanced Glycation/Glycoxidation End Products (AGEs)", "relationship_type": "causal", "source_pmcid": "PMC12386734" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "AGE-modified glycoproteins accumulate due to impaired clearance.", "mechanism": "Serum AGEs increase with CKD and frailty, inversely associated with physical performance.", "protein": "AGEs", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386734" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "High SOD2 expression correlates with improved muscle growth and performance.", "protein": "SOD2", "relationship_type": "protective", "source_pmcid": "PMC12386734" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "NRF2 activation upregulates antioxidant enzymes, promoting muscle regeneration and adaptation.", "protein": "NRF2", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "RyR1 is a glycoprotein; glycosylation may affect channel stability/function.", "mechanism": "Oxidative modifications (S-glutathionylation/S-nitrosylation) of RyR1 alter calcium release, affecting muscle contraction and fatigue.", "protein": "RyR1", "relationship_type": "causal", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "S-glutathionylation of TnIf enhances Ca2+ sensitivity, maintaining muscle function after exercise.", "protein": "TnIf", "relationship_type": "protective", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "VEGF is a secreted glycoprotein; glycosylation required for secretion/activity.", "mechanism": "Exercise-induced upregulation of VEGF promotes angiogenesis and muscle regeneration.", "protein": "VEGF", "relationship_type": "protective", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "CODAS Syndrome", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "LONP1 mutations cause muscle impairment and hypotonia.", "protein": "LONP1", "relationship_type": "causal", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "High GRX2 expression linked to improved muscle growth and athletic performance.", "protein": "GRX2", "relationship_type": "protective", "source_pmcid": "PMC12386734" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation noted.", "mechanism": "Increased expression correlates with better muscle function and resistance to oxidative stress.", "protein": "PRDX3/PRDX5/TRX2", "relationship_type": "protective", "source_pmcid": "PMC12386734" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "CD19 is glycosylated, affecting surface expression and recognition.", "mechanism": "CAR-T cells and exosomes target CD19 on B cells, inducing cytotoxicity and remission.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "high", "disease": "HER2-positive breast cancer brain metastases", "glycan_involvement": "HER2 glycosylation modulates receptor stability and antibody/exosome binding.", "mechanism": "CAR-NK cell-derived exosomes cross the blood-brain barrier and selectively target HER2+ tumor cells.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "MSLN glycosylation influences cell surface localization and immune recognition.", "mechanism": "CAR-T cell-derived exosomes loaded with paclitaxel target MSLN+ lung cancer cells, enhancing drug delivery.", "protein": "Mesothelin (MSLN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "EGFR glycosylation affects ligand binding and exosome targeting.", "mechanism": "CAR-T cell-derived exosomes targeting EGFR inhibit tumor growth in TNBC models.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "CD22 glycosylation modulates antigenicity and cell surface expression.", "mechanism": "CAR-T cells and exosomes targeting CD22 induce cytotoxicity in B-ALL.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "CD7 glycosylation affects immune cell interactions.", "mechanism": "CAR-T cells and exosomes targeting CD7 induce cytotoxicity in T-ALL.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "CD70 glycosylation may influence immune recognition.", "mechanism": "CAR-T cells and exosomes targeting CD70 show limited efficacy in ccRCC.", "protein": "CD70", "protein_enriched": { "function": "Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells (PubMed:28011863, PubMed:28011864, PubMed:8387892). The CD7", "gene_name": "CD70", "glycan_count": 16, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G06247RL", "G08918WF", "G27058EU", "G29299MO", "G40574BA", "G45395BF", "G57776ZS", "G63041LO", "G69521XL", "G79666IR", "G41247ZX", "G57321FI", "G49108TO" ], "uniprot_id": "P32970" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "PD-L1 glycosylation regulates stability and immune checkpoint function.", "mechanism": "PD-L1 levels in CAR-T cell-derived exosomes can monitor tumor immune escape and guide immunotherapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "KRAS is not a glycoprotein; no direct glycan involvement.", "mechanism": "KRAS mutation-associated RNA/protein in CAR-T exosomes enables early diagnosis and recurrence monitoring.", "protein": "KRAS", "relationship_type": "biomarker", "source_pmcid": "PMC12386737" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "CXCL10 glycosylation may affect chemokine activity and stability.", "mechanism": "CAR-M cell-derived exosomes with high CXCL10 enhance T cell activation and M1 macrophage polarization, promoting antitumor immunity.", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386737" }, { "confidence": "high", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "N-glycosylation affects APP trafficking and aggregation.", "mechanism": "Accumulation in damaged axons due to disrupted axonal transport; gold standard for DAI detection.", "protein": "\u03b2-amyloid precursor protein (\u03b2-APP)", "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "high", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "O-glycosylation modulates tau aggregation and stability.", "mechanism": "Elevated blood tau after injury reflects axonal degeneration and correlates with poor outcome.", "protein": "Tau protein", "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "high", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycosylation influences GFAP filament assembly.", "mechanism": "Serum and tissue GFAP levels indicate astrocytic injury and BBB disruption; correlate with severity.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycosylation affects S100-B secretion and stability.", "mechanism": "Serum S100-B increases after brain injury; correlates with injury degree but limited by BBB integrity.", "protein": "S100-B", "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "high", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Spectrin glycosylation may affect proteolytic susceptibility.", "mechanism": "SNTF fragment detects degenerating axons not marked by \u03b2-APP; reflects calpain-mediated cytoskeletal breakdown.", "protein": "Spectrin alpha-II (SNTF fragment)", "protein_enriched": { "function": "Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane", "gene_name": "SPTAN1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G71908WU", "G28681TP" ], "uniprot_id": "Q13813" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycosylation regulates AQP4 membrane localization and function.", "mechanism": "Reduced AQP4 expression impairs glymphatic clearance, perpetuating axonal and oligodendrocyte injury.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycoprotein components of HDL mediate CNS transport.", "mechanism": "Elevated HDL in serum during first week post-injury is an independent predictor of DAI.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Traumatic Brain Injury (TBI)", "glycan_involvement": "Glycosylation may affect UCH-L1 stability and activity.", "mechanism": "Serum and CSF UCH-L1 levels correlate with CNS injury and clinical outcome.", "protein": "Ubiquitin C-terminal hydrolase L1 (UCH-L1)", "protein_enriched": { "function": "Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:22212137, PubMed", "gene_name": "UCHL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09936" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycosylation influences NSE secretion.", "mechanism": "Serum NSE increases acutely after DAI; correlates with outcome in early phase.", "protein": "Neuron-specific enolase (NSE)", "protein_enriched": { "function": "Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell sur", "gene_name": "Eno2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07323" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386751" }, { "confidence": "medium", "disease": "Diffuse Axonal Injury (DAI)", "glycan_involvement": "Glycosylation may regulate spectrin interactions.", "mechanism": "Disruption in \u03b2IV-spectrin impairs axonal conduction and contributes to persistent dysfunction.", "protein": "\u03b2IV-spectrin", "relationship_type": "causal", "source_pmcid": "PMC12386751" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "PROM2 is a transmembrane glycoprotein; glycosylation may affect its membrane localization and ligand interactions.", "mechanism": "PROM2 inhibits Notch signaling, impairs cardiac progenitor cell differentiation, promotes cardiomyocyte aging and fibrosis.", "protein": "PROM2", "protein_enriched": { "function": "Protease inhibitor that inhibits trypsin and trypsin-like serine proteases (in vitro). Inhibits plasmin and thrombin with lower efficiency (in vitro)", "gene_name": "SERPINA9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q86WD7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386803" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "PTPN22 is glycosylated; glycosylation may regulate its stability and T cell signaling.", "mechanism": "PTPN22 upregulation in CD4+ T cells correlates with increased effector/memory T cells, promoting inflammation and fibrosis.", "protein": "PTPN22", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "FAM175B is a glycoprotein; glycosylation may influence its complex formation and stability.", "mechanism": "FAM175B upregulation is linked to DNA repair in cardiomyocytes under oxidative stress and negatively correlates with NK cell abundance.", "protein": "FAM175B", "protein_enriched": { "function": "Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to site", "gene_name": "BABAM1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G41247ZX", "G49108TO" ], "uniprot_id": "Q9NWV8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "LRRTM4 is a transmembrane glycoprotein; glycosylation may modulate cell\u2013cell interactions.", "mechanism": "LRRTM4 promotes cardiac fibroblast activation via Wnt/\u03b2-catenin signaling, contributing to fibrosis.", "protein": "LRRTM4", "protein_enriched": { "function": "May contribute to specialized endoplasmic reticulum functions in neurons", "gene_name": "SEZ6L2", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G06356OH", "G15169WU", "G22310AV", "G31665QC", "G35107SO", "G46503DX", "G48414YA", "G56784JY", "G74728JK", "G75983OB", "G89205CJ", "G51653BI", "G47518TP", "G62765YT", "G69521XL", "G80920RR", "G53434XO", "G29068FM", "G43417UB", "G16125XL", "G83633GK" ], "uniprot_id": "Q6UXD5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Collagens are glycoproteins; glycosylation affects extracellular matrix structure.", "mechanism": "COL19A1 is central in immune gene networks enriched for antigen presentation and T cell signaling.", "protein": "COL19A1", "protein_enriched": { "function": "", "gene_name": "CYSTM1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H1C7" }, "relationship_type": "network hub", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "MHC class II proteins are N-glycosylated, affecting antigen presentation.", "mechanism": "HLA-DOB is central in antigen presentation pathways, influencing immune activation in DCM.", "protein": "HLA-DOB", "protein_enriched": { "function": "Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cle", "gene_name": "HLA-DRB4", "glycan_count": 11, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G08290VR", "G11314AS", "G27058EU", "G31852PQ", "G41247ZX", "G47644PP", "G62765YT", "G79666IR", "G80920RR", "G83460ZZ", "G92275SC" ], "uniprot_id": "P13762" }, "relationship_type": "network hub", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Heart Failure", "glycan_involvement": "Glycosylation may regulate PROM2's function in aging cardiomyocytes.", "mechanism": "PROM2 overexpression induces cardiomyocyte aging and hypertrophy.", "protein": "PROM2", "protein_enriched": { "function": "Protease inhibitor that inhibits trypsin and trypsin-like serine proteases (in vitro). Inhibits plasmin and thrombin with lower efficiency (in vitro)", "gene_name": "SERPINA9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q86WD7" }, "relationship_type": "causal", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Viral Myocarditis", "glycan_involvement": "Glycosylation may affect FAM175B's stability and interactions in immune cells.", "mechanism": "FAM175B upregulation may suppress NK cell function, delaying viral clearance and promoting progression to DCM.", "protein": "FAM175B", "protein_enriched": { "function": "Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to site", "gene_name": "BABAM1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62765YT", "G41247ZX", "G49108TO" ], "uniprot_id": "Q9NWV8" }, "relationship_type": "causal", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Chronic Cardiac Failure (CHF)", "glycan_involvement": "Glycosylation may modulate PTPN22's phosphatase activity.", "mechanism": "PTPN22 upregulation is associated with increased left ventricular size, decreased ejection fraction, and T cell dysregulation.", "protein": "PTPN22", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12386803" }, { "confidence": "medium", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation may influence PROM2's drug binding and receptor interactions.", "mechanism": "PROM2 interacts with small molecules (e.g., colchicine), suggesting druggability for modulating cardiac progenitor differentiation.", "protein": "PROM2", "protein_enriched": { "function": "Protease inhibitor that inhibits trypsin and trypsin-like serine proteases (in vitro). Inhibits plasmin and thrombin with lower efficiency (in vitro)", "gene_name": "SERPINA9", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q86WD7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386803" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "PPAR\u03b3 is glycosylated, affecting stability and activity.", "mechanism": "Downregulation by CKDB-322 suppresses adipogenesis and fat accumulation.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates transcriptional activity.", "mechanism": "CKDB-322 downregulates C/EBP\u03b1, inhibiting adipocyte differentiation.", "protein": "C/EBP\u03b1", "protein_enriched": { "function": "", "gene_name": "KRT3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12035" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Hepatic steatosis (fatty liver)", "glycan_involvement": "SREBP-1c glycosylation affects nuclear translocation.", "mechanism": "CKDB-322 reduces SREBP-1c expression, decreasing hepatic lipogenesis.", "protein": "SREBP-1c", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation regulates enzyme activity.", "mechanism": "CKDB-322 suppresses ACC, reducing fatty acid synthesis.", "protein": "ACC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation influences FAS stability.", "mechanism": "CKDB-322 downregulates FAS, limiting lipid accumulation.", "protein": "FAS", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates mitochondrial localization.", "mechanism": "CKDB-322 upregulates CPT-1\u03b1, enhancing fatty acid oxidation.", "protein": "CPT-1\u03b1", "relationship_type": "protective", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation affects DNA binding and activity.", "mechanism": "CKDB-322 increases PPAR\u03b1, promoting lipid catabolism.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC12386854" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation regulates coactivator function.", "mechanism": "CKDB-322 upregulates PGC-1\u03b1, improving mitochondrial biogenesis and energy metabolism.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "protective", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates kinase activity.", "mechanism": "CKDB-322 activates AMPK, increasing energy expenditure and reducing adiposity.", "protein": "AMPK", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Leptin is a glycoprotein; glycosylation is essential for secretion and receptor binding.", "mechanism": "CKDB-322 reduces leptin levels, reflecting decreased adiposity and improved leptin sensitivity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386854" }, { "confidence": "high", "disease": "Endometriosis-associated infertility", "glycan_involvement": "Glycosylation critical for immunomodulatory and adhesive functions.", "mechanism": "Reduced glycodelin impairs embryo adhesion and endometrial receptivity.", "protein": "Glycodelin", "protein_enriched": { "function": "Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tiss", "gene_name": "PAEP", "glycan_count": 42, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G06110VR", "G06356OH", "G13290KJ", "G14696LD", "G23294PN", "G24835MQ", "G25837HW", "G27165KO", "G31916IQ", "G33671BL", "G33876UV", "G44339YF", "G46455GO", "G49874UX", "G51705EB", "G56749GV", "G66116BW", "G70418MS", "G72291OX", "G72667IM", "G75269BP", "G76012OT", "G76675AB", "G80858MF", "G81877PA", "G82463GQ", "G84452RH", "G86705PH", "G87889NL", "G92654OJ", "G93856AJ", "G02628JF", "G08110WX", "G22310AV", "G59821FL", "G60923RB", "G62765YT", "G81198YO", "G82592ZH", "G85228QD", "G87051GH", "G95977AE" ], "uniprot_id": "P09466" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "high", "disease": "Endometrial receptivity breakdown", "glycan_involvement": "N-glycosylation modulates integrin-ligand binding.", "mechanism": "Downregulation leads to poor embryo attachment and implantation failure.", "protein": "Integrin alphaVbeta3", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "high", "disease": "Repeated implantation failure (RIF)", "glycan_involvement": "Glycosylation required for LIF stability and receptor interaction.", "mechanism": "Reduced LIF expression impairs endometrial receptivity and implantation.", "protein": "Leukemia Inhibitory Factor (LIF)", "protein_enriched": { "function": "LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of ", "gene_name": "LIF", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "P15018" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "high", "disease": "Angiogenesis abnormality", "glycan_involvement": "N-glycosylation affects VEGF-A secretion and receptor binding.", "mechanism": "VEGF-A overexpression drives aberrant vascularization in lesions.", "protein": "Vascular Endothelial Growth Factor A (VEGF-A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation influences complement activation and stability.", "mechanism": "Elevated plasma C9 reflects immune activation and lesion presence.", "protein": "Complement C9", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Angiogenesis abnormality", "glycan_involvement": "N-glycosylation required for VEGF binding.", "mechanism": "Upregulated in plasma of endometriosis patients; modulates VEGF signaling.", "protein": "Neuropilin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation affects anticoagulant activity.", "mechanism": "Altered levels in plasma panel for endometriosis diagnosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation may affect cell surface localization.", "mechanism": "Hsp70-positive circulating endometrial cells indicate disease presence.", "protein": "Heat Shock Protein 70 (Hsp70)", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation modulates leukocyte adhesion.", "mechanism": "Elevated in pre-diagnostic blood samples; reflects immune activation.", "protein": "Intercellular Adhesion Molecule 2 (ICAM2)", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "Glycosylation may influence secretion and immune interactions.", "mechanism": "Elevated in plasma; associated with innate immune activation.", "protein": "S100A9", "relationship_type": "biomarker", "source_pmcid": "PMC12386890" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation critical for cell surface localization and function.", "mechanism": "Regulates leukocyte recruitment to inflamed skin; inhibition reduces inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "O-glycosylation affects cross-linking and barrier integrity.", "mechanism": "Downregulated in AD; restoration improves barrier function.", "protein": "Involucrin", "protein_enriched": { "function": "Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia", "gene_name": "IVL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07476" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation modulates protein stability and hydration.", "mechanism": "Loss leads to barrier dysfunction and increased disease risk.", "protein": "Filaggrin", "protein_enriched": { "function": "Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis", "gene_name": "FLG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20930" }, "relationship_type": "causal", "source_pmcid": "PMC12386966" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "O-glycosylation required for cornified envelope formation.", "mechanism": "Reduced expression correlates with impaired barrier; restoration is protective.", "protein": "Loricrin", "protein_enriched": { "function": "Major keratinocyte cell envelope protein", "gene_name": "LORICRIN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23490" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated in AD; reduction indicates anti-inflammatory effect.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "N-glycosylation affects secretion.", "mechanism": "Promotes neutrophil recruitment; inhibition reduces inflammation.", "protein": "IL-8", "protein_enriched": { "function": "Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also ", "gene_name": "CXCL8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10145" }, "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "N-glycosylation modulates chemokine activity.", "mechanism": "Attracts Th2 cells; elevated in AD, reduction is therapeutic.", "protein": "CCL17 (TARC)", "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "Recruits Th2 cells; inhibition reduces inflammation.", "protein": "CCL22 (MDC)", "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "N-glycosylation affects chemokine gradient formation.", "mechanism": "Promotes immune cell infiltration; inhibition is anti-inflammatory.", "protein": "RANTES (CCL5)", "relationship_type": "biomarker", "source_pmcid": "PMC12386966" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "Mediates chronic inflammation; inhibition reduces inflammatory response.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12386966" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation modulates fibrinogen function and clot formation.", "mechanism": "Elevated FGA indicates activation of coagulation cascade, associated with increased thrombotic risk post-infection and post-vaccination.", "protein": "Fibrinogen alpha chain (FGA)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation affects SAA1 stability and immune signaling.", "mechanism": "SAA1 is an acute-phase reactant elevated in both COVID-19 and post-vaccination states, reflecting systemic inflammation.", "protein": "Serum amyloid A1 (SAA1)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation critical for HP's antioxidant and immune functions.", "mechanism": "HP is upregulated in vaccinated individuals, indicating persistent low-grade inflammation and oxidative stress.", "protein": "Haptoglobin (HP)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "N-glycosylation regulates complement activation and clearance.", "mechanism": "C3 elevation post-vaccination suggests sustained complement activation, contributing to endothelial stress.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation modulates FN1's cell adhesion and matrix functions.", "mechanism": "FN1 upregulation post-vaccination indicates ongoing extracellular matrix remodeling and vascular changes.", "protein": "Fibronectin (FN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "low", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects APOE's lipid transport and neuroimmune interactions.", "mechanism": "APOE elevation in vaccinated individuals may signal increased neuroinflammatory susceptibility.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "high", "disease": "Hypercoagulable state", "glycan_involvement": "N-glycosylation influences fibrinogen polymerization and clot stability.", "mechanism": "FGB is strongly upregulated post-vaccination, indicating a persistent procoagulant state.", "protein": "Fibrinogen beta chain (FGB)", "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates SAA4's immune signaling.", "mechanism": "SAA4 is elevated in both infection and post-vaccination, serving as a marker for acute-phase response.", "protein": "Serum amyloid A4 (SAA4)", "protein_enriched": { "function": "Major acute phase reactant", "gene_name": "SAA4", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G06356OH", "G59626AS", "G82463GQ" ], "uniprot_id": "P35542" }, "relationship_type": "diagnostic biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation regulates complement activity.", "mechanism": "C2 is upregulated in both infection and post-vaccination, reflecting complement system activation.", "protein": "Complement C2", "protein_enriched": { "function": "Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and si", "gene_name": "C2", "glycan_count": 55, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G00912UN", "G06247RL", "G08918WF", "G10486CT", "G12341GU", "G22573RC", "G25418HZ", "G27058EU", "G27947YN", "G28681TP", "G40574BA", "G45395BF", "G48414YA", "G59626AS", "G62765YT", "G70232NH", "G80920RR", "G27126ED", "G34989PA", "G37509XX", "G49018RC", "G49642SA", "G57776ZS", "G58087IP", "G72951AH", "G85554PZ", "G94917XT", "G81263BG", "G94470IW", "G11629QQ", "G14796IU", "G01650EU", "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G31852PQ", "G37399XV", "G39188ZX", "G40206WX", "G41247ZX", "G70101JE", "G82463GQ", "G02030ZB", "G06356OH", "G12580WI", "G22310AV", "G56518TU", "G57776ZU", "G70888PK", "G75983OB", "G78649WQ", "G82830MN", "G83460ZZ", "G95865ZB" ], "uniprot_id": "P06681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "N-glycosylation affects fibrinogen's interaction with platelets and endothelial cells.", "mechanism": "FGG elevation is associated with cardiac stress and risk of cardiovascular events post-infection and post-vaccination.", "protein": "Fibrinogen gamma chain (FGG)", "protein_enriched": { "function": "Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In a", "gene_name": "FGG", "glycan_count": 109, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G06247RL", "G06356OH", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G11911BT", "G14972EH", "G15664MX", "G16125XL", "G18647XP", "G19379ID", "G20706XG", "G22572EH", "G23294PN", "G23505EP", "G25079LO", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G30970QQ", "G31852PQ", "G31916IQ", "G34029GR", "G35029YA", "G36191CD", "G36442WJ", "G37412TK", "G37509XX", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G43223CG", "G43734MM", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G46902YN", "G47644PP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50073PQ", "G51653BI", "G57317CE", "G57776ZU", "G58087IP", "G58954YZ", "G59626AS", "G60033FS", "G60145BJ", "G61256FT", "G62765YT", "G63980BQ", "G65184UU", "G70441OD", "G70619PT", "G72291OX", "G72747WU", "G72787SB", "G72790NZ", "G75850OP", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80920RR", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84467IZ", "G84862VB", "G85269DF", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G90659AW", "G91365ZQ", "G92135MA", "G92551JA", "G94470IW", "G95865ZB", "G98129XB", "G98611JV", "G49108TO" ], "uniprot_id": "P02679" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387044" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "AST is a glycoprotein; glycosylation affects stability and clearance.", "mechanism": "Plasma AST levels indicate hepatocellular injury.", "protein": "Aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12387057" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "ALT is glycosylated; glycosylation modulates serum half-life.", "mechanism": "ALT elevation signals liver injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387057" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation regulates SCD-1 localization and function.", "mechanism": "SCD-1 activity alters fatty acid composition, impacting metabolic syndrome risk.", "protein": "Stearoyl-CoA desaturase-1 (SCD-1)", "relationship_type": "causal", "source_pmcid": "PMC12387057" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Lipase activity influences dietary fat absorption, affecting obesity risk.", "protein": "Pancreatic lipase", "protein_enriched": { "function": "Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows consi", "gene_name": "PNLIP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16233" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387057" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation critical for transporter stability and function.", "mechanism": "Transporters regulate bile acid homeostasis, influencing lipid absorption and metabolic health.", "protein": "Bile acid transporters", "relationship_type": "causal", "source_pmcid": "PMC12387057" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects SCD-1 activity.", "mechanism": "SCD-1 modulates fatty acid profiles, impacting cardiovascular risk.", "protein": "Stearoyl-CoA desaturase-1 (SCD-1)", "relationship_type": "causal", "source_pmcid": "PMC12387057" }, { "confidence": "low", "disease": "Chronic inflammatory disease", "glycan_involvement": "Glycosylation supports enzyme function.", "mechanism": "Efficient lipase-mediated absorption of omega-3 fatty acids reduces inflammation.", "protein": "Pancreatic lipase", "protein_enriched": { "function": "Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows consi", "gene_name": "PNLIP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16233" }, "relationship_type": "protective", "source_pmcid": "PMC12387057" }, { "confidence": "medium", "disease": "Acute kidney allograft rejection", "glycan_involvement": "Glycosylation affects P-glycoprotein stability and function, modulating drug transport.", "mechanism": "Genetic polymorphisms in ABCB1 affect tacrolimus pharmacokinetics, influencing immunosuppression and rejection risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "medium", "disease": "Infection (post-transplant)", "glycan_involvement": "Glycosylation modulates transporter activity, impacting drug clearance.", "mechanism": "Altered P-glycoprotein function changes tacrolimus levels, increasing infection risk with high drug exposure.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "high", "disease": "Acute kidney allograft rejection", "glycan_involvement": "HLA glycosylation affects antigen presentation and antibody recognition.", "mechanism": "Mismatch or presence of donor-specific anti-HLA antibodies leads to immune-mediated rejection.", "protein": "HLA class I/II molecules", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "high", "disease": "Acute kidney allograft rejection", "glycan_involvement": "DSA glycosylation influences effector function and complement activation.", "mechanism": "DSA presence predicts and mediates antibody-mediated rejection.", "protein": "Donor-specific anti-HLA antibodies (DSA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12387067" }, { "confidence": "medium", "disease": "Chronic allograft dysfunction (fibrosis, atrophy)", "glycan_involvement": "Glycosylation modulates immune recognition and chronic inflammation.", "mechanism": "Chronic immune activation against HLA leads to fibrosis and atrophy.", "protein": "HLA class I/II molecules", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "medium", "disease": "Chronic allograft dysfunction (fibrosis, atrophy)", "glycan_involvement": "Glycosylation affects transporter function and drug exposure.", "mechanism": "High intrapatient variability in tacrolimus (partly due to P-glycoprotein) is linked to chronic lesions.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "medium", "disease": "Chronic allograft dysfunction (fibrosis, atrophy)", "glycan_involvement": "DSA glycosylation modulates pathogenicity.", "mechanism": "Persistent DSA leads to chronic antibody-mediated injury.", "protein": "Donor-specific anti-HLA antibodies (DSA)", "relationship_type": "causal", "source_pmcid": "PMC12387067" }, { "confidence": "medium", "disease": "Infection (post-transplant)", "glycan_involvement": "Glycosylation affects HLA stability and immune interactions.", "mechanism": "Adequate HLA-mediated immune response protects against infection; excessive immunosuppression impairs this.", "protein": "HLA class I/II molecules", "relationship_type": "protective", "source_pmcid": "PMC12387067" }, { "confidence": "low", "disease": "Acute kidney allograft rejection", "glycan_involvement": "Not glycosylated; included for mechanism completeness.", "mechanism": "FKBP12 binds tacrolimus, inhibiting calcineurin and T-cell activation.", "protein": "Tacrolimus-binding proteins (FKBP12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387067" }, { "confidence": "low", "disease": "Infection (post-transplant)", "glycan_involvement": "Glycosylation may affect antibody effector function.", "mechanism": "High DSA levels may indicate over-immunosuppression, increasing infection risk.", "protein": "Donor-specific anti-HLA antibodies (DSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12387067" }, { "confidence": "high", "disease": "Advanced Melanoma", "glycan_involvement": "SIgA glycosylation is essential for mucosal immune function and microbiota interaction.", "mechanism": "High baseline fecal SIgA levels are associated with favorable clinical outcomes and improved survival in anti-PD-1 therapy.", "protein": "Secretory Immunoglobulin A (SIgA)", "relationship_type": "biomarker", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Advanced Melanoma", "glycan_involvement": "Zonulin is a glycoprotein modulating tight junctions; glycosylation affects its stability and function.", "mechanism": "High baseline fecal zonulin levels predict longer overall survival in patients undergoing anti-PD-1 therapy.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Advanced Melanoma", "glycan_involvement": "Calprotectin is glycosylated, which may influence its inflammatory activity.", "mechanism": "High baseline fecal calprotectin levels are associated with poor survival outcomes and increased risk of disease progression during anti-PD-1 therapy.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Gut Barrier Dysfunction", "glycan_involvement": "SIgA glycosylation enables binding to mucins and microbial antigens.", "mechanism": "SIgA maintains intestinal homeostasis by immune exclusion of pathogens and shaping microbiota composition.", "protein": "Secretory Immunoglobulin A (SIgA)", "relationship_type": "protective", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Gut Barrier Dysfunction", "glycan_involvement": "Glycosylation modulates zonulin's receptor interactions.", "mechanism": "Elevated zonulin increases intestinal permeability, contributing to barrier dysfunction.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "causal", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Intestinal Inflammation", "glycan_involvement": "Glycosylation may affect calprotectin's stability and immune signaling.", "mechanism": "Elevated calprotectin reflects neutrophil-driven inflammation in the gut.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387085" }, { "confidence": "medium", "disease": "Intestinal Inflammation", "glycan_involvement": "SIgA glycan structures mediate anti-inflammatory effects.", "mechanism": "SIgA reduces inflammation by preventing pathogen invasion and promoting commensal colonization.", "protein": "Secretory Immunoglobulin A (SIgA)", "relationship_type": "protective", "source_pmcid": "PMC12387085" }, { "confidence": "medium", "disease": "Intestinal Inflammation", "glycan_involvement": "Glycosylation influences zonulin's activity and immune signaling.", "mechanism": "Zonulin-mediated tight junction disassembly can trigger local and systemic inflammation.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "causal", "source_pmcid": "PMC12387085" }, { "confidence": "medium", "disease": "Advanced Melanoma", "glycan_involvement": "SIgA glycosylation is critical for its immunomodulatory functions.", "mechanism": "Enhancing SIgA responses may improve anti-cancer immunity and outcomes in immunotherapy.", "protein": "Secretory Immunoglobulin A (SIgA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387085" }, { "confidence": "medium", "disease": "Advanced Melanoma", "glycan_involvement": "Targeting glycosylation could alter zonulin's function.", "mechanism": "Modulating zonulin activity may restore barrier integrity and improve immunotherapy efficacy.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387085" }, { "confidence": "high", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "EGFR glycosylation modulates ligand binding and drug sensitivity.", "mechanism": "Activating EGFR mutations drive NSCLC; targeted by TKIs.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "HER2 glycosylation affects antibody binding and receptor dimerization.", "mechanism": "HER2 amplification drives tumor growth; targeted by trastuzumab.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "medium", "disease": "ALK-rearranged NSCLC", "glycan_involvement": "ALK glycosylation may influence receptor stability and signaling.", "mechanism": "ALK rearrangement drives oncogenesis; targeted by crizotinib.", "protein": "ALK", "protein_enriched": { "function": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differe", "gene_name": "ALK", "glycan_count": 1, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UM73" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "medium", "disease": "NTRK fusion-positive tumors", "glycan_involvement": "NTRK1 glycosylation modulates receptor function.", "mechanism": "NTRK1 fusions drive tumorigenesis; targeted by TRK inhibitors.", "protein": "NTRK1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q02583" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "medium", "disease": "NTRK fusion-positive tumors", "glycan_involvement": "NTRK3 glycosylation modulates receptor function.", "mechanism": "NTRK3 fusions drive tumorigenesis; targeted by TRK inhibitors.", "protein": "NTRK3", "protein_enriched": { "function": "Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways,", "gene_name": "NTRK3", "glycan_count": 2, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G40574BA", "G63041LO" ], "uniprot_id": "Q16288" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "KRAS is prenylated, not glycosylated; glycoprotein context via EGFR.", "mechanism": "KRAS mutations drive cancer; targeted by sotorasib in combination with anti-EGFR.", "protein": "KRAS", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "high", "disease": "BRCA1/2-deficient cancers", "glycan_involvement": "No direct glycosylation; context via glycoprotein DNA repair complexes.", "mechanism": "BRCA1 loss impairs DNA repair; synthetic lethality with PARP inhibitors.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "causal", "source_pmcid": "PMC12387099" }, { "confidence": "high", "disease": "BRCA1/2-deficient cancers", "glycan_involvement": "No direct glycosylation; context via nuclear protein complexes.", "mechanism": "PARP inhibition induces synthetic lethality in BRCA-deficient cells.", "protein": "PARP1", "protein_enriched": { "function": "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, Pub", "gene_name": "PARP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P09874" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387099" }, { "confidence": "medium", "disease": "PTEN-deficient cancers", "glycan_involvement": "No direct glycosylation; PI3K pathway includes glycoprotein receptors.", "mechanism": "PTEN loss activates PI3K pathway; synthetic lethality with PI3K\u03b2 inhibitors.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "causal", "source_pmcid": "PMC12387099" }, { "confidence": "medium", "disease": "ARID1A-deficient cancers", "glycan_involvement": "No direct glycosylation; chromatin context.", "mechanism": "ARID1A deficiency creates vulnerability to EZH2/ATR inhibitors.", "protein": "ARID1A", "protein_enriched": { "function": "Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry ou", "gene_name": "ARID1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O14497" }, "relationship_type": "causal", "source_pmcid": "PMC12387099" }, { "confidence": "high", "disease": "Negative energy balance (NEB)", "glycan_involvement": "Lactose is a glycan; its synthesis reflects glycosylation status in mammary gland.", "mechanism": "Low milk lactose indicates NEB due to reduced glucose availability for lactose synthesis.", "protein": "Lactose", "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "high", "disease": "Subclinical ketosis", "glycan_involvement": "Lactose reduction reflects altered glycan metabolism in mammary gland.", "mechanism": "Low milk lactose correlates with elevated NEFA/BHBA, markers of ketosis.", "protein": "Lactose", "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "medium", "disease": "Mastitis", "glycan_involvement": "Lactose loss reflects disruption of glycan synthesis during inflammation.", "mechanism": "Decreased milk lactose is associated with mastitis and increased somatic cell count.", "protein": "Lactose", "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "high", "disease": "Metabolic disturbances", "glycan_involvement": "Altered lactose synthesis indicates glycan metabolism imbalance.", "mechanism": "Milk lactose <4.70% is linked to metabolic disturbances in early lactation.", "protein": "Lactose", "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "medium", "disease": "Metabolic disturbances", "glycan_involvement": "Albumin is N-glycosylated; changes may reflect metabolic status.", "mechanism": "Serum albumin positively correlates with milk lactose, reflecting protein and glycan metabolism.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "ALT is glycosylated; activity may reflect glycan-mediated enzyme regulation.", "mechanism": "Elevated ALT in high lactose cows suggests increased hepatic activity for lactose synthesis.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "medium", "disease": "Elevated somatic cell count", "glycan_involvement": "Lactose decrease reflects impaired glycan synthesis during inflammation.", "mechanism": "Low lactose is associated with increased somatic cell count, indicating inflammation.", "protein": "Lactose", "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "low", "disease": "Mastitis", "glycan_involvement": "CRP is heavily glycosylated; glycan changes reflect inflammation.", "mechanism": "CRP measured as an inflammatory marker; may correlate with low lactose in mastitis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "GGT is glycosylated; glycan status may affect enzyme activity.", "mechanism": "GGT measured as a liver function marker; may be altered in metabolic stress.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387217" }, { "confidence": "high", "disease": "Metabolic disturbances", "glycan_involvement": "Efficient lactose synthesis reflects healthy glycan metabolism.", "mechanism": "High milk lactose (\u22654.70%) is associated with better metabolic health and higher milk yield.", "protein": "Lactose", "relationship_type": "protective", "source_pmcid": "PMC12387217" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "WNT5A is a glycoprotein; glycosylation may affect its secretion and signaling.", "mechanism": "Epigenetic silencing (DNA methylation and histone modification) of WNT5A represses its expression, contributing to OS pathogenesis.", "protein": "WNT5A", "relationship_type": "causal", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "VEGF glycosylation is essential for its secretion and function.", "mechanism": "NSUN2-mediated m5C methylation stabilizes VEGF mRNA, promoting angiogenesis and metastasis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387225" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "HDGF glycosylation supports its extracellular activity.", "mechanism": "NSUN2-mediated m5C methylation increases HDGF mRNA stability, enhancing tumor growth and metastasis.", "protein": "HDGF", "protein_enriched": { "function": "Acts as a transcriptional repressor (PubMed:17974029). Has mitogenic activity for fibroblasts (PubMed:11751870, PubMed:26845719). Heparin-binding protein (PubMed:15491618)", "gene_name": "HDGF", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P51858" }, "relationship_type": "causal", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "CXCL12 glycosylation affects chemokine gradient formation.", "mechanism": "DNMT1-mediated promoter methylation suppresses CXCL12 expression, impairing T cell homing and increasing metastasis.", "protein": "CXCL12", "protein_enriched": { "function": "Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions ", "gene_name": "CXCL12", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P48061" }, "relationship_type": "causal", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "MHC class I glycosylation is critical for surface expression and immune recognition.", "mechanism": "DNMT1 overexpression leads to promoter hypermethylation and downregulation of MHC class I, impairing antigen presentation and immune evasion.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12387225" }, { "confidence": "medium", "disease": "Chemoresistant Osteosarcoma", "glycan_involvement": "BCL2 glycosylation may affect its stability and function.", "mechanism": "BRD4 overexpression upregulates BCL2, promoting cell survival and resistance to apoptosis.", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "CD47 glycosylation is required for its 'don't eat me' signal.", "mechanism": "CD47 blockade enhances phagocytosis of OS cells; efficacy is increased when combined with epigenetic drugs.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Immunosuppressive Tumor Microenvironment", "glycan_involvement": "PD-L1 glycosylation stabilizes its cell surface expression.", "mechanism": "Histone deacetylation via HDAC6/STAT3 pathway upregulates PD-L1, contributing to immune evasion.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387225" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "SERPINE2 glycosylation affects its inhibitory activity.", "mechanism": "AI-based biomarker discovery links SERPINE2 to memory B cell infiltration and OS prognosis.", "protein": "SERPINE2", "protein_enriched": { "function": "Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin", "gene_name": "SERPINE2", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G14972EH", "G27058EU", "G30740WO", "G34989PA", "G40574BA", "G41071NU", "G45395BF", "G83460ZZ", "G87661QW", "G49108TO", "G80920RR", "G43417UB" ], "uniprot_id": "P07093" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387225" }, { "confidence": "medium", "disease": "Osteosarcoma", "glycan_involvement": "CREG1 glycosylation may influence its secretion and activity.", "mechanism": "CREG1 promoter hypermethylation reduces its expression, contributing to OS progression; demethylating agents restore its function.", "protein": "CREG1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387225" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "Glycosylation is essential for receptor stability and iron uptake.", "mechanism": "Transferrin receptor levels decrease with higher PFAS exposure, indicating altered cellular iron demand.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "high", "disease": "Iron overload", "glycan_involvement": "Glycosylation affects ferritin secretion and stability.", "mechanism": "Ferritin levels increase with PFAS exposure, suggesting enhanced iron storage.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation modulates transferrin receptor binding and iron delivery.", "mechanism": "Transferrin saturation increases with PFAS exposure, reflecting altered iron transport.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Iron overload", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Lower transferrin receptor levels with PFAS exposure may indicate reduced cellular iron uptake.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation influences ferritin secretion during inflammation.", "mechanism": "Ferritin is an acute-phase reactant; increased levels may reflect inflammation or iron overload.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Oxidative stress-related disorders", "glycan_involvement": "N-glycosylation affects antioxidant capacity.", "mechanism": "Altered transferrin saturation with PFAS exposure may contribute to oxidative stress.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation regulates receptor turnover in inflammatory states.", "mechanism": "Transferrin receptor levels are modulated by inflammation and PFAS exposure.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "Glycosylation impacts ferritin stability.", "mechanism": "Low ferritin is a marker for iron deficiency; PFAS exposure may confound interpretation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "medium", "disease": "Iron overload", "glycan_involvement": "N-glycosylation modulates iron binding.", "mechanism": "High transferrin saturation with PFAS exposure may indicate iron overload risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "low", "disease": "Oxidative stress-related disorders", "glycan_involvement": "Glycosylation affects receptor-mediated iron uptake under stress.", "mechanism": "Altered transferrin receptor levels may reflect oxidative stress induced by PFAS.", "protein": "Transferrin receptor", "relationship_type": "biomarker", "source_pmcid": "PMC12387234" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Prolactin is glycosylated, which affects its stability and receptor binding.", "mechanism": "High prolactin levels increase insulin resistance and impair insulin secretion.", "protein": "Prolactin", "protein_enriched": { "function": "Prolactin acts primarily on the mammary gland by promoting lactation", "gene_name": "PRL", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01236" }, "relationship_type": "causal", "source_pmcid": "PMC12387363" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Cortisol is a glycoprotein hormone; glycosylation affects its secretion and activity.", "mechanism": "Cortisol promotes gluconeogenesis and protein breakdown, raising blood glucose.", "protein": "Cortisol", "relationship_type": "causal", "source_pmcid": "PMC12387363" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Insulin glycosylation is critical for its folding and receptor interaction.", "mechanism": "Elevated insulin levels indicate metabolic stress and risk for metabolic syndrome.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "medium", "disease": "Pregnancy complications", "glycan_involvement": "TSH is heavily glycosylated, which modulates its bioactivity.", "mechanism": "Reduced TSH levels during stress may affect thyroid function and pregnancy outcomes.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "GST is not a glycoprotein; no direct glycan involvement.", "mechanism": "GST activity increases transiently in response to anesthesia-induced oxidative stress.", "protein": "GST", "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "medium", "disease": "Organ dysfunction", "glycan_involvement": "Albumin glycosylation affects its antioxidant capacity and transport function.", "mechanism": "Albumin levels reflect liver function and systemic stress.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Fibrinogen glycosylation modulates clot formation and stability.", "mechanism": "Fibrinogen levels are predictive of thrombophilia and coagulation status.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "CRP glycosylation affects its immune recognition and clearance.", "mechanism": "CRP is an acute-phase glycoprotein elevated during inflammation.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "Glycosylation influences prolactin's immunomodulatory effects.", "mechanism": "Prolactin modulates immune cell function and can disrupt immune homeostasis.", "protein": "Prolactin", "protein_enriched": { "function": "Prolactin acts primarily on the mammary gland by promoting lactation", "gene_name": "PRL", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01236" }, "relationship_type": "causal", "source_pmcid": "PMC12387363" }, { "confidence": "medium", "disease": "Endocrine stress response", "glycan_involvement": "FT3 is glycosylated; glycan status affects hormone stability and activity.", "mechanism": "Reduced FT3 levels indicate stress-induced changes in thyroid hormone metabolism.", "protein": "Tri-iodothyronine (FT3)", "relationship_type": "biomarker", "source_pmcid": "PMC12387363" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Heme deficiency impairs AMPK signaling and mitochondrial function, leading to insulin resistance.", "protein": "ALAS1", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products", "gene_name": "ALAS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13196" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Glucose intolerance", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Reduced heme synthesis disrupts muscle glucose uptake and glycogen metabolism.", "protein": "ALAS1", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products", "gene_name": "ALAS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13196" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Heme deficiency accelerates muscle atrophy and loss of strength with aging.", "protein": "ALAS1", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products", "gene_name": "ALAS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13196" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Anemia (sideroblastic/XLSA)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Impaired heme synthesis in erythroid cells causes ineffective erythropoiesis and iron accumulation.", "protein": "ALAS2", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:14643893, PubMed:21252495, PubM", "gene_name": "ALAS2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22557" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "medium", "disease": "Mitochondrial dysfunction", "glycan_involvement": "Glycosylation may affect ETC complex stability, but not directly discussed.", "mechanism": "Heme deficiency impairs ETC complex assembly, reducing oxidative phosphorylation.", "protein": "Cytochrome c oxidase", "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "N-glycosylation required for proper assembly and trafficking of NADPH oxidase subunits.", "mechanism": "Heme deficiency reduces ROS generation and neutrophil bactericidal activity.", "protein": "NADPH oxidase", "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "HO-1 induction mitigates oxidative stress and modulates inflammation; deficiency blunts immune response.", "protein": "HO-1 (Heme oxygenase-1)", "relationship_type": "protective", "source_pmcid": "PMC12387456" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Impaired heme export disrupts muscle mitochondrial function and strength, especially with aging.", "protein": "Flvcr1a", "protein_enriched": { "function": "Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis (PubMed:37100056, PubMed:38693265, PubMed:38778100, ", "gene_name": "FLVCR1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Y0" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Accelerated aging", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Chronic heme deficiency promotes aging phenotypes via mitochondrial and metabolic decline.", "protein": "ALAS1", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products", "gene_name": "ALAS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13196" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Glycogen storage dysregulation", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Heme deficiency suppresses AMPK, leading to excessive glycogen accumulation in muscle.", "protein": "ALAS1", "protein_enriched": { "function": "Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products", "gene_name": "ALAS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P13196" }, "relationship_type": "causal", "source_pmcid": "PMC12387456" }, { "confidence": "high", "disease": "Diminished ovarian reserve (DOR)", "glycan_involvement": "FSH glycosylation affects its bioactivity and half-life.", "mechanism": "FSH levels rise as inhibin B and estrogen decline, indicating reduced follicular cohort size.", "protein": "FSH", "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "high", "disease": "Diminished ovarian reserve (DOR)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Circulating inhibin B declines with follicle loss, reflecting ovarian reserve.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "high", "disease": "Diminished ovarian reserve (DOR)", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "AMH declines with age and follicle pool depletion, serving as a proxy for ovarian reserve.", "protein": "AMH", "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "high", "disease": "Menopausal transition", "glycan_involvement": "Glycosylation influences FSH receptor binding and clearance.", "mechanism": "FSH increases as ovarian hormone output declines, marking menopausal transition.", "protein": "FSH", "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "medium", "disease": "Menopausal transition", "glycan_involvement": "Glycosylation essential for function.", "mechanism": "Inhibin A decreases with reduced corpus luteum activity, contributing to FSH rise.", "protein": "Inhibin A", "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "medium", "disease": "Menopause", "glycan_involvement": "Glycosylation affects LH bioactivity.", "mechanism": "LH levels rise post-menopause due to loss of negative feedback from ovarian hormones.", "protein": "LH", "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "medium", "disease": "Premature ovarian insufficiency (POI)", "glycan_involvement": "Galectin-9 binds glycans to modulate immune responses.", "mechanism": "Exosome-delivered galectin-9 attenuates autoimmune T cell activity, protecting ovarian cells in POI models.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387586" }, { "confidence": "medium", "disease": "Premature ovarian insufficiency (POI)", "glycan_involvement": "PD-1 glycosylation regulates immune checkpoint function.", "mechanism": "Exosome-delivered PD-1 suppresses T cell-mediated ovarian damage in POI models.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12387586" }, { "confidence": "medium", "disease": "Early menopause", "glycan_involvement": "BRCA1 is glycosylated; glycosylation may affect stability/function.", "mechanism": "BRCA1 mutations impair DNA repair, leading to reduced AMH, lower ovarian reserve, and earlier menopause.", "protein": "BRCA1", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (Pub", "gene_name": "BRCA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G00912UN", "G48414YA", "G34071GT", "G49108TO" ], "uniprot_id": "P38398" }, "relationship_type": "causal", "source_pmcid": "PMC12387586" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Low inhibin B reflects reduced follicle number and fertility potential.", "protein": "Inhibin B", "protein_enriched": { "function": "Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypoth", "gene_name": "INHA", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P05111" }, "relationship_type": "biomarker", "source_pmcid": "PMC12387586" }, { "confidence": "high", "disease": "Anterior Chamber Inflammation", "glycan_involvement": "FN glycosylation mediates ECM interactions and immune modulation.", "mechanism": "FN monolayer formation on Collamer shields lens from immune recognition, reducing inflammation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "high", "disease": "Foreign Body Reaction", "glycan_involvement": "Glycosylation of FN supports host compatibility.", "mechanism": "FN layer derived from host on Collamer prevents immune system recognition of lens as foreign.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "medium", "disease": "Lens Opacification", "glycan_involvement": "Glycosylated FN forms stable ECM barrier.", "mechanism": "FN monolayer inhibits cell and protein adhesion, maintaining lens transparency.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "medium", "disease": "Biofilm Formation", "glycan_involvement": "FN glycosylation modulates cell-ECM interactions.", "mechanism": "FN coating on Collamer reduces monocyte and platelet activation, limiting biofilm formation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "medium", "disease": "Anterior Chamber Inflammation", "glycan_involvement": "Collagen glycosylation enhances FN binding.", "mechanism": "Collagen in Collamer promotes FN adhesion, reducing inflammatory cell response.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "low", "disease": "Cataract", "glycan_involvement": "FN glycosylation stabilizes ECM barrier.", "mechanism": "FN layer on Collamer and IPCL haptics may reduce protein/cell adhesion, lowering cataract risk.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "low", "disease": "Glaucoma", "glycan_involvement": "FN glycosylation supports ECM structure.", "mechanism": "FN-coated lens surfaces facilitate aqueous humor circulation, reducing glaucoma risk.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC12388130" }, { "confidence": "medium", "disease": "Foreign Body Reaction", "glycan_involvement": "Altered FN glycosylation or absence affects immune recognition.", "mechanism": "Limited FN adhesion on IPCL/acrylic lenses allows other proteins to bind, triggering immune response.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12388130" }, { "confidence": "low", "disease": "Lens Opacification", "glycan_involvement": "Reduced FN glycosylation impairs ECM barrier.", "mechanism": "Insufficient FN coating on acrylic lenses may permit cell/protein adhesion, risking opacification.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC12388130" }, { "confidence": "low", "disease": "Anterior Chamber Inflammation", "glycan_involvement": "Laminin glycosylation regulates cell-ECM binding.", "mechanism": "Laminin, like FN, modulates cell adhesion and inflammation in the anterior chamber.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12388130" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "O-glycosylation affects stability and detection as a biomarker.", "mechanism": "Serum cytokeratin 18 reduction reflects decreased hepatocyte apoptosis in response to probiotic therapy.", "protein": "Cytokeratin 18", "protein_enriched": { "function": "Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to th", "gene_name": "KRT18", "glycan_count": 6, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G57321FI", "G83646BJ", "G47012YE", "G62765YT", "G64527OM" ], "uniprot_id": "P05783" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388143" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation modulates secretion and receptor binding.", "mechanism": "Pro-inflammatory cytokine upregulated via TLR4/NF-\u03baB pathway, driving hepatic inflammation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12388143" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation affects cytokine stability and activity.", "mechanism": "Produced via NLRP3 inflammasome activation, promotes liver inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12388143" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Pro-inflammatory cytokine elevated in MASH, reduced by probiotic intervention.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12388143" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Glycosylation necessary for stability and anti-inflammatory activity.", "mechanism": "Anti-inflammatory cytokine upregulated by probiotics, counteracts hepatic inflammation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12388143" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation essential for cell surface expression and LPS recognition.", "mechanism": "Activated by LPS, triggers NF-\u03baB signaling and cytokine production in liver.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12388143" }, { "confidence": "medium", "disease": "Alcoholic liver disease", "glycan_involvement": "Glycosylation affects enzyme activity and serum half-life.", "mechanism": "Serum GGT levels reduced by probiotic therapy, reflecting improved liver function.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12388143" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation influences stability and function.", "mechanism": "Serum albumin increased by probiotics, indicating improved liver synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388143" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Component glycoproteins require glycosylation for assembly/function.", "mechanism": "Activation leads to IL-1\u03b2/IL-18 release, driving hepatic inflammation; suppressed by probiotics.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12388143" }, { "confidence": "low", "disease": "MASH", "glycan_involvement": "Glycosylation may affect nuclear localization and activity.", "mechanism": "Probiotic-induced modulation of PPAR\u03b3 signaling improves lipid metabolism and reduces steatosis.", "protein": "PPAR\u03b3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388143" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA is heavily glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "PROTAC-mediated degradation of HA blocks viral entry and replication.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "NA glycosylation affects enzymatic activity and antigenicity.", "mechanism": "PROTACs degrade NA, inhibiting viral release and overcoming drug resistance.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "E protein is glycosylated; glycosylation is critical for viral assembly and host cell entry.", "mechanism": "PROTACs degrade E protein, reducing viral replication and infectivity.", "protein": "Envelope protein E (Flavivirus)", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P03314" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is extensively glycosylated; glycans shield epitopes and modulate ACE2 binding.", "mechanism": "PROTACs or peptide-based degraders target S protein, preventing viral entry.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "E protein lacks glycosylation, facilitating small-molecule targeting.", "mechanism": "PROTACs proposed to degrade E protein, disrupting viral assembly and release.", "protein": "Envelope protein E (SARS-CoV-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "AIDS (HIV-1)", "glycan_involvement": "CypA is a host glycoprotein; glycosylation may affect protein stability and interactions.", "mechanism": "PROTACs degrade CypA, inhibiting HIV-1 replication in T cells.", "protein": "Cyclophilin A (CypA)", "protein_enriched": { "function": "Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic", "gene_name": "PPIA", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27915IV", "G37995HC", "G49906RN", "G60033FS", "G62765YT", "G49108TO", "G70994MS", "G80920RR" ], "uniprot_id": "P62937" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates S protein binding and viral entry.", "mechanism": "PROTACs or peptide degraders reduce ACE2 levels, blocking SARS-CoV-2 entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TMPRSS2 is glycosylated; glycosylation may affect protease activity.", "mechanism": "PROTACs degrade TMPRSS2, preventing S protein activation and viral fusion.", "protein": "Transmembrane protease serine 2 (TMPRSS2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "HBsAg is glycosylated; glycosylation is essential for secretion and immune recognition.", "mechanism": "PROTACs targeting HBsAg reduce viral load and antigenemia.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "AIDS (HIV-1)", "glycan_involvement": "Nef is not glycosylated; no direct glycan involvement.", "mechanism": "PROTACs degrade Nef, restoring immune function and inhibiting viral infectivity.", "protein": "HIV-1 Nef protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388152" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects receptor conformation and ligand binding.", "mechanism": "Mediates platelet aggregation via fibrinogen binding; targeted by antiplatelet drugs.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388159" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates receptor trafficking and ligand sensitivity.", "mechanism": "PAFR activation drives inflammation and platelet aggregation, contributing to atherosclerotic plaque formation.", "protein": "Platelet-activating factor receptor (PAFR)", "protein_enriched": { "function": "Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G", "gene_name": "PTAFR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P25105" }, "relationship_type": "causal", "source_pmcid": "PMC12388159" }, { "confidence": "high", "disease": "Myocardial infarction (MI)", "glycan_involvement": "Glycosylation influences receptor surface expression and drug binding.", "mechanism": "ADP-mediated platelet activation via P2Y12 is central to thrombus formation; inhibited by clopidogrel.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388159" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation regulates receptor activation and platelet function.", "mechanism": "Platelet aggregation via GPIIb/IIIa contributes to arterial occlusion in stroke.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388159" }, { "confidence": "medium", "disease": "Thrombotic thrombocytopenic purpura (TTP)", "glycan_involvement": "Glycosylation required for ADAMTS13 secretion and activity.", "mechanism": "Diclofenac-induced inhibition of ADAMTS13 leads to TTP by impairing vWF cleavage.", "protein": "ADAMTS13", "protein_enriched": { "function": "Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation", "gene_name": "ADAMTS13", "glycan_count": 16, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G96881BQ", "G29068FM", "G43417UB", "G53434XO", "G22310AV", "G84452RH", "G15169WU", "G47748JZ", "G36855WW", "G06356OH", "G33791AF", "G37881RL", "G47518TP", "G48414YA", "G74728JK", "G49108TO" ], "uniprot_id": "Q76LX8" }, "relationship_type": "causal", "source_pmcid": "PMC12388159" }, { "confidence": "medium", "disease": "Inflammation-driven diseases", "glycan_involvement": "Glycosylation affects receptor function and inflammatory signaling.", "mechanism": "PAFR signaling mediates platelet activation and systemic inflammation in diseases like renal dysfunction, cancer, and autoimmune disorders.", "protein": "Platelet-activating factor receptor (PAFR)", "protein_enriched": { "function": "Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G", "gene_name": "PTAFR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P25105" }, "relationship_type": "causal", "source_pmcid": "PMC12388159" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation essential for cell adhesion and platelet-endothelial interactions.", "mechanism": "P-selectin expression on platelets marks activation and is associated with thrombotic risk.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12388159" }, { "confidence": "medium", "disease": "Peripheral artery disease (PAD)", "glycan_involvement": "Glycosylation modulates receptor activity and platelet adhesion.", "mechanism": "Platelet aggregation via GPIIb/IIIa contributes to PAD pathogenesis.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388159" }, { "confidence": "low", "disease": "Renal dysfunction", "glycan_involvement": "Glycosylation impacts receptor signaling in renal tissues.", "mechanism": "PAFR-mediated inflammation and platelet activation contribute to renal disease progression.", "protein": "Platelet-activating factor receptor (PAFR)", "protein_enriched": { "function": "Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G", "gene_name": "PTAFR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P25105" }, "relationship_type": "causal", "source_pmcid": "PMC12388159" }, { "confidence": "high", "disease": "Cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation regulates receptor function and drug response.", "mechanism": "Central mediator of platelet aggregation in CVD; targeted by antiplatelet therapies.", "protein": "Glycoprotein IIb/IIIa (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388159" }, { "confidence": "high", "disease": "Malnutrition in hemodialysis patients", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect stability and half-life.", "mechanism": "Low serum albumin is a key component of GNRI and reflects poor nutritional status.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "high", "disease": "Hypoalbuminemia", "glycan_involvement": "Altered glycosylation may occur during inflammation.", "mechanism": "Malnutrition and inflammation reduce albumin synthesis, leading to hypoalbuminemia.", "protein": "Serum albumin", "relationship_type": "causal", "source_pmcid": "PMC12388193" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "CRP is N-glycosylated; glycosylation affects its function and clearance.", "mechanism": "CRP is elevated in inflammatory states, which are common in HD patients and contribute to malnutrition.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect its serum levels.", "mechanism": "Ferritin reflects iron stores; altered in anemia and inflammation in HD patients.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB); glycosylation affects receptor binding.", "mechanism": "LDL-C levels are monitored in HD patients; dyslipidemia is common and linked to malnutrition.", "protein": "Low-density lipoprotein cholesterol (LDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I); glycosylation modulates function.", "mechanism": "HDL-C levels inversely associated with cardiovascular risk; altered in malnutrition.", "protein": "High-density lipoprotein cholesterol (HDL-C)", "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Transferrin is N-glycosylated; glycosylation status (e.g., sialylation) is clinically relevant.", "mechanism": "Transferrin transports iron; levels may be altered in anemia and malnutrition.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "IgG Fc N-glycosylation modulates immune response.", "mechanism": "IgG levels and glycosylation patterns change during inflammation in HD patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Highly glycosylated; glycan changes reflect inflammatory status.", "mechanism": "AGP is an acute-phase protein elevated in inflammation, which is linked to malnutrition.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "high", "disease": "Protein-energy wasting (PEW)", "glycan_involvement": "Glycosylation may affect albumin's stability and diagnostic accuracy.", "mechanism": "Low albumin is a diagnostic criterion for PEW in HD patients.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12388193" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "SHBG is a glycoprotein; glycosylation affects its stability and binding affinity.", "mechanism": "Reduced SHBG leads to increased free androgens, contributing to hyperandrogenism in PCOS.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "AMH is a glycoprotein; glycosylation may affect secretion and receptor interaction.", "mechanism": "Elevated AMH levels correlate with increased androgen production and impaired follicle development in PCOS.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388250" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "IGFBP-1 is a glycoprotein; glycosylation may regulate its stability and IGF-1 binding.", "mechanism": "Low IGFBP-1 increases IGF-1 bioavailability, enhancing androgen synthesis in PCOS.", "protein": "Insulin-like growth factor binding protein-1 (IGFBP-1)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "LH is a glycoprotein; glycosylation affects receptor binding and bioactivity.", "mechanism": "Elevated LH stimulates ovarian androgen production, central to PCOS pathophysiology.", "protein": "Luteinizing hormone (LH)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "FSH is a glycoprotein; glycosylation modulates receptor interaction.", "mechanism": "Reduced FSH impairs follicle maturation, contributing to anovulation in PCOS.", "protein": "Follicle-stimulating hormone (FSH)", "relationship_type": "biomarker", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "Insulin glycosylation not specified in article.", "mechanism": "Hyperinsulinemia promotes androgen synthesis and inhibits SHBG production, exacerbating PCOS.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "No glycosylation specified.", "mechanism": "Elevated kisspeptin drives increased GnRH/LH secretion, contributing to PCOS neuroendocrine dysfunction.", "protein": "Kisspeptin", "protein_enriched": { "function": "Metastasis suppressor protein in malignant melanomas and in some breast cancers. May regulate events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-te", "gene_name": "KISS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q15726" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12388250" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "No glycosylation specified.", "mechanism": "Elevated NPY modulates GnRH/LH pulsatility and energy balance, implicated in PCOS pathogenesis.", "protein": "Neuropeptide Y (NPY)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12388250" }, { "confidence": "medium", "disease": "Polycystic ovary syndrome (PCOS)", "glycan_involvement": "Leptin is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Elevated leptin levels observed in PCOS, associated with obesity and metabolic dysfunction.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Infertility", "glycan_involvement": "AMH glycosylation may affect bioactivity.", "mechanism": "Elevated AMH impairs follicle development and ovulation, contributing to infertility in PCOS.", "protein": "Anti-M\u00fcllerian hormone (AMH)", "relationship_type": "biomarker", "source_pmcid": "PMC12388250" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation enhances water solubility and cellular uptake.", "mechanism": "Induces apoptosis and ferroptosis in cancer cells via mitochondrial pathway and ROS generation.", "protein": "\u03b1-hederin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation modulates cytotoxicity and selectivity.", "mechanism": "Triggers mitochondrion-mediated apoptosis via PI3K/Akt pathway modulation.", "protein": "Macranthoside B (MB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Sugar moieties improve solubility and efficacy.", "mechanism": "Protects chondrocytes by inhibiting NF-\u03baB/MAPK signaling and cartilage degradation.", "protein": "Hederacoside-C (HDC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation status affects protein stability and function.", "mechanism": "Downregulation by Hederacoside-C reduces neutrophil degranulation and repairs intestinal barrier.", "protein": "S100A9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "high", "disease": "Acute Lung Inflammation", "glycan_involvement": "Glycosylation influences receptor-ligand interactions.", "mechanism": "Direct antagonism by SMG-1 saponin inhibits neutrophil activation.", "protein": "FMLP receptor (FPR1)", "protein_enriched": { "function": "High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:10514456, PubMed:15153520, PubMed:2161213, PubMed:2176894). Binding of fMLP to ", "gene_name": "FPR1", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P21462" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation critical for transporter function and substrate specificity.", "mechanism": "Effluxes hederagenin and glycosides, reducing intracellular drug concentration and efficacy.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12388280" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation may regulate Nrf2 stability and activity.", "mechanism": "Inhibition by hederagenin/glycosides increases ROS, promoting cancer cell apoptosis.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "medium", "disease": "Streptococcus pneumoniae infection", "glycan_involvement": "Glycosylation affects toxin structure and host interaction.", "mechanism": "Hederagenin neutralizes PLY, preventing cell lysis and inflammation.", "protein": "Pneumolysin (PLY)", "protein_enriched": { "function": "Catalyzes the isomerization of L-xylulose-5-phosphate to L-ribulose-5-phosphate. Is involved in the anaerobic L-ascorbate utilization", "gene_name": "ulaE", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C1B2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation may modulate apoptotic signaling.", "mechanism": "Upregulated by hederagenin/glycosides, promoting apoptosis.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation influences anti-apoptotic function.", "mechanism": "Downregulated by hederagenin/glycosides, facilitating apoptosis.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388280" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects substrate specificity and stability.", "mechanism": "Synthetic peptide biomarkers cleaved by neutrophil elastase indicate heightened activity in cancer.", "protein": "Neutrophil elastase", "protein_enriched": { "function": "Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of", "gene_name": "ELANE", "glycan_count": 18, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G93279DZ", "G00395TQ", "G08290VR", "G11870QZ", "G27058EU", "G28681TP", "G29299MO", "G47644PP", "G47950XN", "G61334IA", "G82348BZ", "G00912UN", "G11314AS", "G25637MV", "G36379GD", "G59626AS", "G72291OX", "G95865ZB" ], "uniprot_id": "P08246" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "high", "disease": "Adenocarcinoma", "glycan_involvement": "Glycosylation modulates enzyme activity and trafficking.", "mechanism": "Overexpression detected by intracellular sensors in adenocarcinoma cells.", "protein": "Cathepsin B", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Exosomal protein glycosylation patterns are disease-specific.", "mechanism": "Nanoenzyme sensor arrays detect exosomal glycoproteins for cancer diagnosis.", "protein": "Exosomal proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation in uEV proteins reflects disease state.", "mechanism": "Fluorescence detection of uEV glycoproteins enables prostate cancer diagnosis.", "protein": "Urinary extracellular vesicle proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA glycosylation affects immunoreactivity and diagnostic accuracy.", "mechanism": "Electrochemical sensor detects PSA glycoprotein for prostate cancer screening.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "medium", "disease": "Acute myocardial infarction", "glycan_involvement": "Glycosylation modulates miRNA carrier protein stability.", "mechanism": "DNA photonic wire detects miRNA-associated glycoproteins elevated in AMI.", "protein": "miRNAs-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "medium", "disease": "Renal cell cancer", "glycan_involvement": "Cancer alters glycosylation patterns of serum proteins.", "mechanism": "Surface-enhanced Raman scattering of blood glycoproteins differentiates RCC patients.", "protein": "Renal cell cancer-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation changes in exosomes reflect tumor progression.", "mechanism": "Mass spectrometry imaging of exosomal glycoproteins correlates with survival and metastasis.", "protein": "Gastric cancer exosomal glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation patterns distinguish tumor subtypes.", "mechanism": "t-SNE analysis of exosomal glycoproteins links subpopulations to metastatic status.", "protein": "Breast cancer exosomal glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388605" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Antibody glycosylation impacts selectivity and stability in sensor devices for autoimmune diagnostics.", "protein": "Antibody glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388605" }, { "confidence": "high", "disease": "Subclinical mastitis", "glycan_involvement": "O-antigen is a glycan-rich structure; its biosynthesis is reduced by DMY, lowering inflammation.", "mechanism": "O-antigen biosynthesis by gut E. coli is linked to increased mastitis severity via immune activation.", "protein": "O-antigen (E. coli)", "relationship_type": "causal", "source_pmcid": "PMC12388848" }, { "confidence": "high", "disease": "Subclinical mastitis", "glycan_involvement": "Muramic acid is a glycan component of bacterial cell walls; its abundance reflects bacterial glycoprotein turnover.", "mechanism": "Muramic acid levels in plasma correlate with mastitis severity and gut Proteobacteria abundance.", "protein": "Muramic acid-containing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "high", "disease": "Subclinical mastitis", "glycan_involvement": "Bacterial glycoproteins may mediate butyrate production and mucosal glycan interactions.", "mechanism": "Increased abundance of butyrate-producing bacteria (Roseburia, Coprococcus) correlates with reduced mastitis severity.", "protein": "Butyric acid-producing glycoproteins (Roseburia, Coprococcus)", "relationship_type": "protective", "source_pmcid": "PMC12388848" }, { "confidence": "medium", "disease": "Subclinical mastitis", "glycan_involvement": "Glycoprotein-bile acid interactions modulate immune signaling.", "mechanism": "Elevated secondary bile acids (e.g., deoxycholic acid) bind host glycoproteins, reducing inflammation.", "protein": "Secondary bile acid-binding glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12388848" }, { "confidence": "medium", "disease": "Subclinical mastitis", "glycan_involvement": "Glycosylation may affect prostaglandin receptor function.", "mechanism": "Prostaglandin derivatives (e.g., 15-deoxy-D-12,14-PGJ2) are linked to mastitis severity and gut Proteobacteria.", "protein": "Prostaglandin-associated glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation modulates enzyme stability and activity.", "mechanism": "DMY increases antioxidant glycoprotein activity, reducing oxidative stress in mastitis.", "protein": "Antioxidant glycoproteins (e.g., catalase, T-AOC)", "relationship_type": "protective", "source_pmcid": "PMC12388848" }, { "confidence": "low", "disease": "Subclinical mastitis", "glycan_involvement": "Albumin glycosylation status can change in inflammation.", "mechanism": "Serum albumin levels are measured but not significantly altered by DMY; may reflect systemic inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "low", "disease": "Subclinical mastitis", "glycan_involvement": "Globulin glycosylation may affect immune function.", "mechanism": "Serum globulin levels are measured; not significantly changed by DMY.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "medium", "disease": "Subclinical mastitis", "glycan_involvement": "AKP is a glycoprotein; glycosylation affects its activity.", "mechanism": "Serum AKP tends to decrease with DMY, possibly reflecting reduced inflammation.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "low", "disease": "Subclinical mastitis", "glycan_involvement": "LDH glycosylation may be altered in inflammation.", "mechanism": "Serum LDH is measured; not significantly changed by DMY.", "protein": "Lactate dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC12388848" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation affects receptor localization and ligand binding.", "mechanism": "Modulation by flavonoids (quercetin, hyperoside) enhances cytotoxicity of antineoplastic drugs via receptor binding, affecting tumor proliferation and immune modulation.", "protein": "A2B adenosine receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388873" }, { "confidence": "medium", "disease": "Chemoresistance", "glycan_involvement": "Glycosylation status may influence receptor function and drug response.", "mechanism": "A2B receptor signaling contributes to chemoresistance in TNBC; modulation by glycosylated flavonoids may overcome resistance.", "protein": "A2B adenosine receptor", "relationship_type": "causal", "source_pmcid": "PMC12388873" }, { "confidence": "high", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation required for proper folding and drug transport activity.", "mechanism": "Flavonoids in AM infusion inhibit P-gp, increasing intracellular retention of antineoplastic drugs.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388873" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation essential for VEGF secretion and activity.", "mechanism": "Phenolic compounds in AM infusion inhibit VEGF expression, reducing angiogenesis and tumor growth.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388873" }, { "confidence": "medium", "disease": "Triple-negative breast cancer (TNBC)", "glycan_involvement": "N-glycosylation required for TGF-\u03b2 maturation and secretion.", "mechanism": "AM infusion increases TGF-\u03b2 levels, promoting apoptosis in cancer cells.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388873" }, { "confidence": "medium", "disease": "HPV16-positive cancer", "glycan_involvement": "N-glycosylation influences receptor function.", "mechanism": "Flavonoids from AM infusion bind A2B receptor, potentially modulating immune response and cytotoxicity.", "protein": "A2B adenosine receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388873" }, { "confidence": "high", "disease": "Chemoresistance", "glycan_involvement": "N-glycosylation critical for transporter activity.", "mechanism": "P-gp overexpression leads to drug efflux and chemoresistance; inhibition by flavonoids may reverse resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12388873" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "CD44 glycosylation mediates HA binding and cell targeting.", "mechanism": "Hyaluronic acid-coated melittin liposomes target CD44+ melanoma cells for enhanced cytotoxicity.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "MUC1 O-glycosylation creates tumor-specific epitopes for targeting.", "mechanism": "Calcium carbonate nanoparticles interact with MUC1-overexpressing cancer cells for selective melittin delivery.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "EGFR N-glycosylation affects receptor stability and ligand binding.", "mechanism": "Melittin suppresses EGFR activation, inhibiting proliferation and migration.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "HER2 glycosylation modulates receptor dimerization and activity.", "mechanism": "Melittin inhibits HER2 signaling, reducing tumor progression.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma", "glycan_involvement": "VEGF glycosylation is essential for secretion and receptor interaction.", "mechanism": "Melittin downregulates VEGF, enhancing radiosensitivity and reducing angiogenesis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Integrin glycosylation regulates ligand binding and cell adhesion.", "mechanism": "Melittin nanoparticles functionalized with RGD peptides target \u03b1v\u03b23 integrin on melanoma cells and vasculature.", "protein": "Integrin \u03b1v\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Nucleolin glycosylation may affect aptamer binding and cell surface localization.", "mechanism": "AS1411 aptamer guides melittin-conjugated nanoparticles to nucleolin-expressing breast cancer cells.", "protein": "Nucleolin", "protein_enriched": { "function": "Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding t", "gene_name": "NCL", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G18647XP", "G37399XV", "G41247ZX", "G68735SN" ], "uniprot_id": "P19338" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "low", "disease": "Ovarian Cancer", "glycan_involvement": "FOLR1 glycosylation influences receptor stability and ligand affinity.", "mechanism": "Potential for folate-targeted melittin nanoparticles to selectively kill FOLR1+ ovarian cancer cells.", "protein": "Folate Receptor Alpha (FOLR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Ovarian Cancer", "glycan_involvement": "AXL glycosylation modulates receptor function and cell signaling.", "mechanism": "Melittin-derived nanoparticles deliver siRNA to silence AXL, reducing invasion and metastasis.", "protein": "AXL", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell", "gene_name": "AXL", "glycan_count": 14, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G27058EU", "G84452RH", "G11629QQ", "G12793SR", "G15169WU", "G48414YA", "G52527GH", "G60834IK", "G62765YT", "G81263BG", "G89205CJ", "G93656SY", "G90575OW" ], "uniprot_id": "P30530" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "MMP-2 glycosylation affects enzyme activity and substrate specificity.", "mechanism": "Chlorotoxin-targeted nanoparticles deliver melittin gene to MMP-2+ prostate cancer cells.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388891" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "CDH6 is a glycoprotein; glycosylation may affect cell surface expression and antibody binding.", "mechanism": "CDH6 is overexpressed in ovarian cancer; targeting with ADC (CUSP06) induces DNA damage and apoptosis in tumor cells.", "protein": "Cadherin-6 (CDH6)", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH6", "glycan_count": 79, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G02815KT", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10819WX", "G14972EH", "G23719VF", "G27058EU", "G31028YV", "G39471UU", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G45504EY", "G49955PK", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G70619PT", "G72790NZ", "G75568BH", "G76295SF", "G77547TA", "G79666IR", "G80920RR", "G83646BJ", "G86182NS", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G95177YH", "G00912UN", "G07246CJ", "G10846ZT", "G13131HA", "G28622IK", "G43669FQ", "G49755GI", "G57776ZS", "G58954YZ", "G70441OD", "G80075MS", "G85269DF", "G85282JO", "G85554PZ", "G86880BF", "G87123QX", "G98611JV", "G03644CB", "G06247RL", "G12341GU", "G15127JD", "G27915IV", "G32788FZ", "G47644PP", "G56518TU", "G60834IK", "G63040RU", "G68490OW", "G69521XL", "G70232NH", "G82443XX", "G84225JN", "G01485JJ", "G04854VP", "G10486CT", "G17208MA", "G24528MX", "G61256FT", "G92551JA" ], "uniprot_id": "P55285" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388900" }, { "confidence": "high", "disease": "Renal cell carcinoma", "glycan_involvement": "Glycosylation may regulate CDH6 stability and localization.", "mechanism": "CDH6 is highly expressed in renal cell carcinoma; CUSP06 ADC shows antitumor efficacy.", "protein": "Cadherin-6 (CDH6)", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH6", "glycan_count": 79, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G02815KT", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10819WX", "G14972EH", "G23719VF", "G27058EU", "G31028YV", "G39471UU", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G45504EY", "G49955PK", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G70619PT", "G72790NZ", "G75568BH", "G76295SF", "G77547TA", "G79666IR", "G80920RR", "G83646BJ", "G86182NS", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G95177YH", "G00912UN", "G07246CJ", "G10846ZT", "G13131HA", "G28622IK", "G43669FQ", "G49755GI", "G57776ZS", "G58954YZ", "G70441OD", "G80075MS", "G85269DF", "G85282JO", "G85554PZ", "G86880BF", "G87123QX", "G98611JV", "G03644CB", "G06247RL", "G12341GU", "G15127JD", "G27915IV", "G32788FZ", "G47644PP", "G56518TU", "G60834IK", "G63040RU", "G68490OW", "G69521XL", "G70232NH", "G82443XX", "G84225JN", "G01485JJ", "G04854VP", "G10486CT", "G17208MA", "G24528MX", "G61256FT", "G92551JA" ], "uniprot_id": "P55285" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388900" }, { "confidence": "high", "disease": "Cholangiocarcinoma", "glycan_involvement": "Glycosylation may influence CDH6 cell surface presentation.", "mechanism": "CDH6 is expressed in cholangiocarcinoma; CUSP06 demonstrates tumor growth inhibition.", "protein": "Cadherin-6 (CDH6)", "protein_enriched": { "function": "Cadherins are calcium-dependent cell adhesion proteins. 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They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterog", "gene_name": "CDH6", "glycan_count": 79, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G02815KT", "G04657PL", "G05049YU", "G07755XJ", "G08918WF", "G10819WX", "G14972EH", "G23719VF", "G27058EU", "G31028YV", "G39471UU", "G40834TG", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G45504EY", "G49955PK", "G59626AS", "G60033FS", "G62765YT", "G65184UU", "G70619PT", "G72790NZ", "G75568BH", "G76295SF", "G77547TA", "G79666IR", "G80920RR", "G83646BJ", "G86182NS", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92135MA", "G95177YH", "G00912UN", "G07246CJ", "G10846ZT", "G13131HA", "G28622IK", "G43669FQ", "G49755GI", "G57776ZS", "G58954YZ", "G70441OD", "G80075MS", "G85269DF", "G85282JO", "G85554PZ", "G86880BF", "G87123QX", "G98611JV", "G03644CB", "G06247RL", "G12341GU", "G15127JD", "G27915IV", "G32788FZ", "G47644PP", "G56518TU", "G60834IK", "G63040RU", "G68490OW", "G69521XL", "G70232NH", "G82443XX", "G84225JN", "G01485JJ", "G04854VP", "G10486CT", "G17208MA", "G24528MX", "G61256FT", "G92551JA" ], "uniprot_id": "P55285" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388900" }, { "confidence": "medium", "disease": "Actinic keratosis (AK)", "glycan_involvement": "Glycosylation affects P-gp localization and function.", "mechanism": "Mediates transport of ingenol mebutate across skin barrier, influencing drug efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation modulates STING trafficking and immune signaling.", "mechanism": "Activation by 5-FU enhances anti-tumor immunity against melanoma cells.", "protein": "STING", "protein_enriched": { "function": "Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubM", "gene_name": "STING1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q86WV6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "high", "disease": "Basal cell carcinoma (BCC)", "glycan_involvement": "N-glycosylation required for TLR7 cell surface expression.", "mechanism": "Imiquimod acts as agonist, upregulates immune response and induces apoptosis in tumor cells.", "protein": "Toll-like receptor 7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "high", "disease": "Basal cell carcinoma (BCC)", "glycan_involvement": "N-glycosylation essential for TLR8 function.", "mechanism": "Imiquimod agonism triggers immune activation and tumor cell apoptosis.", "protein": "Toll-like receptor 8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "Glycosylation may affect Bcl-2 stability and apoptotic signaling.", "mechanism": "Diclofenac modulates Bcl-2 expression, activating mitochondrial apoptosis in SCC cells.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "high", "disease": "Actinic keratosis (AK)", "glycan_involvement": "Glycosylation influences COX-2 localization and activity.", "mechanism": "Diclofenac inhibits COX-2, reducing PGE2-mediated tumor growth in AK.", "protein": "COX-2 (PTGS2)", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "PTGS2", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G05724UK", "G25079LO", "G46503DX", "G48584BU", "G62765YT", "G62894KT", "G64527OM", "G70101JE", "G01650EU", "G23294PN", "G80920RR", "G02815KT", "G06110VR", "G31852PQ", "G39188ZX", "G41247ZX" ], "uniprot_id": "P35354" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (SCC)", "glycan_involvement": "Glycosylation modulates VDR stability and signaling.", "mechanism": "Calcipotriol activates VDR, promoting differentiation and anti-tumor immunity in SCC.", "protein": "Vitamin D receptor (VDR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Actinic keratosis (AK)", "glycan_involvement": "Glycosylation affects receptor function and ligand binding.", "mechanism": "Tretinoin/adapalene activate RAR-\u03b2, inducing keratinocyte apoptosis and inhibiting carcinogenesis.", "protein": "Retinoic acid receptor beta (RAR-\u03b2)", "protein_enriched": { "function": "Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression ", "gene_name": "RARB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P10826" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation modulates receptor activity.", "mechanism": "Adapalene/tazarotene activate RAR-\u03b3, exerting anti-proliferative effects on melanoma cells.", "protein": "Retinoic acid receptor gamma (RAR-\u03b3)", "protein_enriched": { "function": "Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression ", "gene_name": "RARG", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13631" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "medium", "disease": "Cutaneous T-cell lymphoma (CTCL)", "glycan_involvement": "Glycosylation influences RXR-\u03b1 nuclear localization.", "mechanism": "Bexarotene activates RXR-\u03b1, inhibiting CTCL cell growth.", "protein": "Retinoid X receptor alpha (RXR-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388908" }, { "confidence": "high", "disease": "Breast adenocarcinoma", "glycan_involvement": "Altered glycosylation of LAMP1 enhances cancer cell adhesion and metastasis.", "mechanism": "Cell surface LAMP1 is highly expressed in tumor cells and TME components (MDSCs, CAFs); correlates with tumor aggressiveness and metastasis.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator o", "gene_name": "LAMP1", "glycan_count": 335, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G00406II", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G07246CJ", "G08918WF", "G10486CT", "G11314AS", "G15664MX", "G17208MA", "G18647XP", "G20210JR", "G23294PN", "G25637MV", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G30248BL", "G31852PQ", "G31986NC", "G33609NS", "G35029YA", "G35253PZ", "G37399XV", "G37509XX", "G37995HC", "G39188ZX", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43769HG", "G45504EY", "G47644PP", "G47702MW", "G48414YA", "G49018RC", "G49906RN", "G49955PK", "G50372IH", "G52527GH", "G55220VL", "G56784JY", "G57317CE", "G57776ZU", "G58087IP", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G64527OM", "G65184UU", "G70101JE", "G70441OD", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G76295SF", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83646BJ", "G84820NF", "G85269DF", "G86880BF", "G88374WZ", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95865ZB", "G96091TT", "G98611JV", "G49108TO", "G03238UC", "G01160VV", "G01521EA", "G02528FI", "G05528SJ", "G12341GU", "G20706XG", "G23505EP", "G26377UA", "G29545VG", "G36442WJ", "G43669FQ", "G44753VC", "G45526EA", "G54010QB", "G56307ZW", "G63040RU", "G63980BQ", "G80479JV", "G84225JN", "G85282JO", "G85554PZ", "G87389XI", "G95046LV", "G30959AM", "G57321FI", "G00031MO", "G64973KT", "G53434XO", "G58001LT", "G88713AC", "G27391WQ", "G12340GZ", "G14260UH", "G48584BU", "G59324HL", "G02030ZB", "G03574QJ", "G03596YS", "G03930BU", "G04657PL", "G04672QB", "G04784US", "G05049YU", "G05933EN", "G06231AO", "G06356OH", "G08290VR", "G08293MJ", "G09528DL", "G10256JP", "G10773YW", "G11009FR", "G11629QQ", "G11870QZ", "G12313PD", "G13131HA", "G14972EH", "G14994KB", "G15169WU", "G20312EM", "G22310AV", "G23719VF", "G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388936" }, { "confidence": "high", "disease": "Colon adenocarcinoma", "glycan_involvement": "Glycosylation changes facilitate tumor cell-ECM interactions and metastasis.", "mechanism": "High LAMP1 expression in tumor and TME; enables PET imaging and correlates with tumor progression.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). 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"G23863VK", "G24377DY", "G25079LO", "G25418HZ", "G25451PN", "G26271XI", "G27622TD", "G29880MM", "G31544HA", "G31916IQ", "G36379GD", "G39619TI", "G40177UP", "G40664HB", "G41126SR", "G43223CG", "G43734MM", "G44211QA", "G44215PV", "G45395BF", "G46524LG", "G46687AB", "G46691LC", "G47012YE", "G47448YK", "G47518TP", "G47737VJ", "G49739MP", "G49874UX", "G50073PQ", "G51640FO", "G54600FO", "G55216FT", "G55383ZG", "G56610MH", "G57776ZS", "G58802FE", "G60177UT", "G60923RB", "G62595EF", "G62894KT", "G65019XG", "G66163OV", "G66621EA", "G66760KM", "G66933CM", "G68490OW", "G69521XL", "G70232NH", "G70619PT", "G72797UR", "G74430RZ", "G74724QE", "G75568BH", "G75607BQ", "G75983OB", "G77547TA", "G77582RK", "G78790NZ", "G79666IR", "G80075MS", "G81263BG", "G82119TF", "G83229XP", "G84452RH", "G84492TS", "G85144OK", "G86795LJ", "G87051GH", "G87123QX", "G87661QW", "G89045VA", "G90093AU", "G90382BL", "G91636VS", "G92062TF", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94854LT", "G94917XT", "G95133RI", "G96577RX", "G03644CB", "G05962QB", "G07810QS", "G09197ZW", "G10039CR", "G10819WX", "G11115RO", "G12745LE", "G16125XL", "G20425TQ", "G23221TW", "G23984SE", "G24084IV", "G24255JV", "G28622IK", "G30769VJ", "G30970QQ", "G32788FZ", "G34617SM", "G35541EV", "G37818NZ", "G39471UU", "G39595FH", "G46902YN", "G49755GI", "G50045TK", "G50282JC", "G50427EO", "G50757KG", "G50856PC", "G52890YB", "G53075ES", "G55132BD", "G56284ZY", "G64394MX", "G65092SV", "G65414LI", "G66537LK", "G67164EE", "G70375MX", "G70888PK", "G70894RY", "G72398FA", "G76868JS", "G79286RS", "G80223IX", "G80669SJ", "G81124ET", "G81637OR", "G82443XX", "G82830MN", "G85677PP", "G85966UN", "G87399DK", "G89827JR", "G92081HT", "G95177YH", "G99668VU", "G99679NM", "G95843QZ", "G14669DU", "G33791AF", "G46503DX", "G51653BI", "G80333GO", "G67299TC", "G70994MS", "G37412TK", "G10997HR", "G01485JJ", "G09831WQ", "G20528HD", "G22589VJ", "G22625SJ", "G24954UD", "G30740WO", "G31596VW", "G34989PA", "G37881RL", "G38663NM", "G57888GL", "G58954YZ", "G59536GA", "G60967DT", "G63381RX", "G64409MC", "G69834CE", "G71784JC", "G72291OX", "G74381CZ", "G78649WQ", "G84349RE", "G91473PK", "G94831VI", "G29931IJ", "G63628AV" ], "uniprot_id": "P11279" }, "relationship_type": "biomarker", "source_pmcid": "PMC12388936" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation may regulate ESR1 stability and signaling.", "mechanism": "ESR1 activation modulates PI3K-AKT and bile secretion pathways, affecting hepatocyte survival and bile acid synthesis.", "protein": "ESR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388948" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "IL6 promotes inflammation via JAK-STAT and PI3K-AKT, exacerbating liver injury.", "protein": "IL6", "relationship_type": "causal", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Potential N-glycosylation affects nuclear localization and function.", "mechanism": "PPARG regulates lipid metabolism and inflammation, modulating PI3K-AKT and bile acid synthesis.", "protein": "PPARG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "O-glycosylation modulates STAT3 transcriptional activity.", "mechanism": "STAT3 activation drives inflammation and fibrosis via PI3K-AKT cross-talk.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "O-glycosylation may regulate TP53 stability.", "mechanism": "TP53 suppresses PI3K-AKT signaling, limiting hepatocyte proliferation and fibrosis.", "protein": "TP53", "relationship_type": "protective", "source_pmcid": "PMC12388948" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation essential for secretion and receptor interaction.", "mechanism": "TNF\u03b1 promotes hepatic inflammation and insulin resistance.", "protein": "TNF\u03b1", "relationship_type": "causal", "source_pmcid": "PMC12388948" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "N-glycosylation required for chemokine activity.", "mechanism": "MCP-1 recruits monocytes, promoting hepatic inflammation and fibrosis.", "protein": "MCP-1 (CCL2)", "relationship_type": "causal", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Possible N-glycosylation affects enzyme stability.", "mechanism": "CYP7A1 catalyzes bile acid synthesis, regulating cholesterol and lipid homeostasis.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Possible N-glycosylation modulates activity.", "mechanism": "CYP8B1 regulates bile acid composition, impacting fat absorption and liver health.", "protein": "CYP8B1", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by ", "gene_name": "Prdx4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z0V5" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388948" }, { "confidence": "medium", "disease": "MASH", "glycan_involvement": "Possible N-glycosylation affects mitochondrial targeting.", "mechanism": "CYP27A1 involved in alternative bile acid synthesis, influencing cholesterol metabolism.", "protein": "CYP27A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388948" }, { "confidence": "high", "disease": "Alpha1-antitrypsin deficiency (AATD)", "glycan_involvement": "Altered N-glycosylation and truncation affect protein stability and function.", "mechanism": "Inherited mutations in AAT (e.g., Pi*Z, Pi*S variants) lead to reduced AAT levels and activity.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12388989" }, { "confidence": "high", "disease": "Emphysema", "glycan_involvement": "Glycosylation status may influence AAT's inhibitory activity and tissue distribution.", "mechanism": "AAT deficiency results in unchecked neutrophil elastase activity, causing lung tissue damage.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Diabetes type-1", "glycan_involvement": "Glycosylation may affect immunomodulatory properties.", "mechanism": "AAT augmentation therapy is being investigated for immune modulation in type-1 diabetes.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Graft-versus-host disease", "glycan_involvement": "Glycan structure could influence anti-inflammatory effects.", "mechanism": "AAT therapy may reduce immune-mediated tissue damage.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation may affect detection and stability in assays.", "mechanism": "AAT levels are monitored to assess inflammation and drug-induced adverse effects.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Drug-induced inflammatory conditions", "glycan_involvement": "Glycan heterogeneity may impact assay accuracy.", "mechanism": "AAT quantification guides therapeutic decisions and predicts outcomes in inflammation.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Immune checkpoint inhibitor-related adverse effects", "glycan_involvement": "Glycosylation may influence immunological interactions.", "mechanism": "AAT levels help monitor immune-related adverse events during therapy.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "biomarker", "source_pmcid": "PMC12388989" }, { "confidence": "low", "disease": "Cataractogenesis", "glycan_involvement": "Glycan modifications may affect aggregation propensity.", "mechanism": "AAT and antioxidants are explored for their role in preventing protein aggregation in cataracts.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "protective", "source_pmcid": "PMC12388989" }, { "confidence": "high", "disease": "Respiratory tract inflammation", "glycan_involvement": "N-glycan branching and sialylation may modulate activity and localization.", "mechanism": "AAT provides >90% anti-elastase activity in the lower respiratory tract, protecting against inflammation.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "protective", "source_pmcid": "PMC12388989" }, { "confidence": "medium", "disease": "Protein aggregation disorders", "glycan_involvement": "Glycosylation and truncation influence aggregation tendency.", "mechanism": "AAT variants prone to aggregation contribute to disease pathology.", "protein": "Alpha1-antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC12388989" }, { "confidence": "high", "disease": "Lipid metabolism disorder", "glycan_involvement": "Glycosylation is required for LPL secretion and activity.", "mechanism": "LPL activity is decreased in lipid metabolism disorder; EGCG and taurine synergistically increase LPL activity, promoting triglyceride hydrolysis.", "protein": "Lipoprotein lipase (LPL)", "protein_enriched": { "function": "Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid cl", "gene_name": "LPL", "glycan_count": 26, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G06356OH", "G08146BT", "G11629QQ", "G20312EM", "G22310AV", "G23863VK", "G25451PN", "G37868ZX", "G42358LZ", "G45495MK", "G47012YE", "G48414YA", "G50427EO", "G51413EV", "G57818FI", "G66163OV", "G71146HJ", "G72797UR", "G75983OB", "G77582RK", "G80920RR", "G81263BG", "G84452RH", "G86795LJ", "G96577RX", "G49108TO" ], "uniprot_id": "P06858" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389005" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "FAS is glycosylated, affecting stability and activity.", "mechanism": "FAS is upregulated in NAFLD; EGCG and taurine suppress FAS expression, reducing hepatic lipogenesis.", "protein": "Fatty acid synthase (FAS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389005" }, { "confidence": "high", "disease": "Lipid metabolism disorder", "glycan_involvement": "No direct glycosylation, but interacts with glycoprotein targets.", "mechanism": "PPAR\u03b1 activation enhances fatty acid oxidation; EGCG and taurine upregulate PPAR\u03b1, improving lipid catabolism.", "protein": "PPAR\u03b1", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q03278" }, "relationship_type": "protective", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "ALP glycosylation affects serum stability and diagnostic value.", "mechanism": "ALP is elevated in hepatic injury; EGCG and taurine reduce ALP levels, indicating improved liver function.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation modulates SOD secretion and activity.", "mechanism": "SOD activity is reduced in oxidative stress; EGCG and taurine increase SOD activity, mitigating oxidative damage.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Glycosylation influences GSH-Px stability.", "mechanism": "GSH-Px activity is decreased in oxidative stress; EGCG and taurine enhance GSH-Px activity, reducing lipid peroxidation.", "protein": "Glutathione peroxidase (GSH-Px)", "relationship_type": "protective", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "ACC glycosylation modulates enzyme activity.", "mechanism": "ACC is upregulated in obesity; EGCG and taurine inhibit ACC, decreasing fatty acid synthesis.", "protein": "Acetyl-CoA carboxylase (ACC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "ALT glycosylation affects serum half-life.", "mechanism": "ALT is elevated in hepatic injury; EGCG and taurine lower ALT, indicating hepatoprotection.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389005" }, { "confidence": "medium", "disease": "Hepatic injury", "glycan_involvement": "AST glycosylation impacts diagnostic accuracy.", "mechanism": "AST is elevated in hepatic injury; EGCG and taurine reduce AST, reflecting improved liver health.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12389005" }, { "confidence": "high", "disease": "Hypertriglyceridemia", "glycan_involvement": "LPL glycosylation is essential for activity.", "mechanism": "Reduced LPL activity leads to hypertriglyceridemia; EGCG and taurine restore LPL function.", "protein": "Lipoprotein lipase (LPL)", "protein_enriched": { "function": "Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid cl", "gene_name": "LPL", "glycan_count": 26, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G06356OH", "G08146BT", "G11629QQ", "G20312EM", "G22310AV", "G23863VK", "G25451PN", "G37868ZX", "G42358LZ", "G45495MK", "G47012YE", "G48414YA", "G50427EO", "G51413EV", "G57818FI", "G66163OV", "G71146HJ", "G72797UR", "G75983OB", "G77582RK", "G80920RR", "G81263BG", "G84452RH", "G86795LJ", "G96577RX", "G49108TO" ], "uniprot_id": "P06858" }, "relationship_type": "causal", "source_pmcid": "PMC12389005" }, { "confidence": "high", "disease": "Dehydration", "glycan_involvement": "Albumin glycosylation may affect its stability and plasma half-life.", "mechanism": "Elevated serum albumin indicates reduced plasma volume due to dehydration.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "high", "disease": "Iron Deficiency", "glycan_involvement": "Ferritin glycosylation affects its serum stability and detection.", "mechanism": "Low serum ferritin reflects depleted iron stores.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Iron Deficiency", "glycan_involvement": "Transferrin glycosylation modulates iron binding and clearance.", "mechanism": "Altered transferrin levels indicate iron transport status.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "GGTP glycosylation affects its enzymatic activity and serum levels.", "mechanism": "Elevated GGTP is a marker of hepatic stress or injury.", "protein": "Gamma-glutamyl transferase (GGTP)", "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "AST glycosylation may influence its release and detection.", "mechanism": "Elevated AST indicates liver cell damage.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "IgG Fc glycosylation modulates immune effector functions.", "mechanism": "Altered IgG glycosylation is associated with systemic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Protein Malnutrition", "glycan_involvement": "Glycosylation may affect albumin's stability and turnover.", "mechanism": "Low serum albumin reflects inadequate protein intake or synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "high", "disease": "Hyperuricemia", "glycan_involvement": "No direct glycan involvement; relevant as a metabolic marker.", "mechanism": "Elevated uric acid is linked to purine-rich diets and metabolic syndrome.", "protein": "Uric Acid", "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "high", "disease": "Renal Dysfunction", "glycan_involvement": "No direct glycan involvement; relevant as a metabolic marker.", "mechanism": "Elevated creatinine indicates impaired renal filtration.", "protein": "Creatinine", "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "medium", "disease": "Cardiovascular Risk", "glycan_involvement": "Sialylation of transferrin modulates its function and clearance.", "mechanism": "Altered transferrin glycoforms are associated with cardiovascular risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389033" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects surface expression and immune recognition.", "mechanism": "Reduced expression on DCs correlates with impaired maturation and migration during acute infection.", "protein": "CD80", "protein_enriched": { "function": "Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation (PubMed:38467718). Acts as the primary auxiliary signal augmenting the MHC", "gene_name": "CD80", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G02886BB", "G80920RR" ], "uniprot_id": "P33681" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389142" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates ligand-receptor interactions.", "mechanism": "Decreased levels on DCs indicate reduced immune activation in severe cases.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389142" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation critical for peptide loading and stability.", "mechanism": "Lower expression on DCs is associated with impaired antigen presentation and immune response.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389142" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation regulates receptor signaling.", "mechanism": "DC depletion and reduced CD40 expression correlate with poor outcomes.", "protein": "CD40", "protein_enriched": { "function": "Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarit", "gene_name": "CD40", "glycan_count": 27, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G31028YV", "G40926MX", "G45395BF", "G59626AS", "G62765YT", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G90659AW", "G02815KT", "G02886BB", "G05724UK", "G28541PG", "G31852PQ", "G41071NU", "G41247ZX", "G42124LM", "G64527OM", "G70441OD" ], "uniprot_id": "P25942" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389142" }, { "confidence": "high", "disease": "Citrobacter rodentium infection", "glycan_involvement": "Glycosylation required for antimicrobial function.", "mechanism": "Induced by IL-22, RegIII\u03b3 promotes bactericidal activity in the gut.", "protein": "RegIII\u03b3", "relationship_type": "protective", "source_pmcid": "PMC12389142" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) infection", "glycan_involvement": "Glycosylation modulates apoptotic signaling.", "mechanism": "TRAIL expression by ILC1s limits CMV replication via cytotoxicity.", "protein": "TRAIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389142" }, { "confidence": "high", "disease": "Salmonella typhimurium infection", "glycan_involvement": "Glycosylation affects cytokine stability and receptor binding.", "mechanism": "IL-22 from ILC3s enhances mucosal immunity but can facilitate infection if dysregulated.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "causal", "source_pmcid": "PMC12389142" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences chemokine receptor trafficking.", "mechanism": "Reduced CCR7 expression impairs DC migration and immune coordination.", "protein": "CCR7", "protein_enriched": { "function": "Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions", "gene_name": "CCR7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P32248" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389142" }, { "confidence": "medium", "disease": "Crohn\u2019s disease", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Altered CXCR5+ DC localization affects Th17/ILC3 interactions and inflammation.", "protein": "CXCR5", "protein_enriched": { "function": "Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph ", "gene_name": "CXCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P32302" }, "relationship_type": "causal", "source_pmcid": "PMC12389142" }, { "confidence": "high", "disease": "Candida albicans infection", "glycan_involvement": "Glycosylation required for cytokine secretion and activity.", "mechanism": "IL-22 promotes epithelial defense and antimicrobial peptide production.", "protein": "IL-22", "protein_enriched": { "function": "Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:17204547). Plays an essential role in the regeneration of epithelial cells to maintain barrier function a", "gene_name": "IL22", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "Q9GZX6" }, "relationship_type": "protective", "source_pmcid": "PMC12389142" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glucuronide glycosylation enhances solubility and bioactivity", "mechanism": "Anti-inflammatory, neuroprotective effects via modulation of inflammatory pathways", "protein": "Apigenin-7-glucuronide", "relationship_type": "protective", "source_pmcid": "PMC12389191" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation at 7-O position increases bioavailability", "mechanism": "Anti-inflammatory and anxiolytic effects", "protein": "Diosmetin 7-O-\u03b2-D-glucopyranoside", "relationship_type": "protective", "source_pmcid": "PMC12389191" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glucoside moiety facilitates vascular effects", "mechanism": "Vasodilatory activity via smooth muscle relaxation", "protein": "Astragalin (Kaempferol-3-O-glucoside)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "medium", "disease": "Gastrointestinal disorders (spasms)", "glycan_involvement": "Ester-linked glycosylation increases stability", "mechanism": "Antispasmodic activity via calcium channel blockade", "protein": "Chlorogenic acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "medium", "disease": "Gastrointestinal disorders (spasms, purgative effect)", "glycan_involvement": "Glycolipid structure essential for spasmogenic activity", "mechanism": "Induces spontaneous contractions in ileum", "protein": "Tricolorin A", "relationship_type": "causal", "source_pmcid": "PMC12389191" }, { "confidence": "high", "disease": "Constipation", "glycan_involvement": "Glycosylation required for laxative effect", "mechanism": "Stimulate intestinal motility via mucosal nerve endings", "protein": "Sennosides A and B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "low", "disease": "Diarrhea", "glycan_involvement": "Glycosylation enhances receptor affinity", "mechanism": "Antidiarrheal effect via M3 muscarinic receptor binding", "protein": "\u03b3-Sitosterol", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "medium", "disease": "Gastrointestinal disorders (spasms)", "glycan_involvement": "Glucoside moiety increases antispasmodic potency", "mechanism": "Inhibits KCl-induced contractions in ileum", "protein": "Luteolin-7-O-glucoside", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation status not specified", "mechanism": "Pro-apoptotic and antiviral effects", "protein": "Arctigenin", "relationship_type": "protective", "source_pmcid": "PMC12389191" }, { "confidence": "low", "disease": "Gastrointestinal disorders (spasms)", "glycan_involvement": "Glycosylation not specified", "mechanism": "Inhibits muscarinic receptors and L-type calcium channels", "protein": "Caffeic acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389191" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosaminoglycan chains are essential for anticoagulant activity.", "mechanism": "Heparin acts as an anticoagulant to prevent thrombosis.", "protein": "Heparin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation affects stability and mucosal absorption.", "mechanism": "Alpha-amylase was tested for anti-inflammatory effects via buccal delivery.", "protein": "Alpha-amylase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04745" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation impacts stability and bioavailability.", "mechanism": "Insulin regulates blood glucose; buccal delivery explored for non-invasive therapy.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation critical for stability and activity; protease inhibitors used to prevent degradation.", "mechanism": "Factor VIII replacement therapy for coagulation deficiency.", "protein": "Factor VIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "medium", "disease": "Viral infections", "glycan_involvement": "Glycosylation modulates receptor binding and half-life.", "mechanism": "Interferons modulate immune response against viruses; buccal delivery investigated.", "protein": "Interferons", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "medium", "disease": "Growth hormone deficiency", "glycan_involvement": "Glycosylation affects stability and absorption.", "mechanism": "Growth hormone replacement for deficiency; buccal delivery explored.", "protein": "Growth hormone", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation influences peptide stability and bioavailability.", "mechanism": "GLP-1 analogs stimulate insulin secretion; buccal delivery tested.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "low", "disease": "Adrenal insufficiency", "glycan_involvement": "Glycosylation affects hormone stability.", "mechanism": "ACTH stimulates cortisol production; buccal delivery considered.", "protein": "Adrenocorticotropin (ACTH)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation impacts peptide stability.", "mechanism": "TRH stimulates TSH release; buccal delivery increases blood thyrotropin.", "protein": "Thyrotropin-releasing hormone (TRH)", "protein_enriched": { "function": "As a component of the hypothalamic-pituitary-thyroid axis, it controls the secretion of thyroid-stimulating hormone (TSH) and is involved in thyroid hormone synthesis regulation. It also operates as m", "gene_name": "TRH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P20396" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "low", "disease": "Digestive disorders", "glycan_involvement": "Glycosylation affects stability and mucosal absorption.", "mechanism": "Secretin regulates pancreatic secretion; buccal delivery explored.", "protein": "Secretin", "protein_enriched": { "function": "Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:25332973). Exerts its biological effects by binding to secretin", "gene_name": "SCT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09683" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389210" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Adiponectin is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Lower plasma adiponectin levels are associated with increased adiposity; VV mixture increased adiponectin/leptin ratio, indicating improved metabolic profile.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389231" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Leptin is glycosylated; glycosylation modulates its receptor binding and activity.", "mechanism": "Elevated leptin levels indicate increased fat mass and inflammation; VV mixture reduced leptin levels, suggesting improved leptin sensitivity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "ACO1 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "HF diet reduced hepatic ACO1 mRNA (fatty acid oxidation); VV mixture restored ACO1 expression, reducing hepatic steatosis.", "protein": "ACO1", "relationship_type": "protective", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "CPT1 glycosylation may regulate mitochondrial localization and function.", "mechanism": "HF diet suppressed CPT1 expression (\u03b2-oxidation); VV mixture restored CPT1, promoting fatty acid oxidation and reducing liver fat.", "protein": "CPT1", "relationship_type": "protective", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation of adiponectin affects its multimerization and insulin-sensitizing activity.", "mechanism": "Higher adiponectin/leptin ratio after VV mixture supplementation is linked to improved insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "NAFLD", "glycan_involvement": "Leptin glycosylation influences its stability and inflammatory signaling.", "mechanism": "Elevated leptin is associated with hepatic inflammation and steatosis; VV mixture reduced leptin, ameliorating NAFLD.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12389231" }, { "confidence": "low", "disease": "Dyslipidemia", "glycan_involvement": "SREBP2 glycosylation may affect nuclear translocation and transcriptional activity.", "mechanism": "SREBP2 regulates cholesterol metabolism; no significant change observed, but referenced as a key lipid metabolism regulator.", "protein": "SREBP2", "relationship_type": "biomarker", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "CYP7A1 glycosylation affects enzyme stability and activity.", "mechanism": "VV mixture may enhance cholesterol catabolism via CYP7A1-mediated bile acid synthesis, lowering serum cholesterol.", "protein": "CYP7A1", "protein_enriched": { "function": "Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to cal", "gene_name": "Sncg", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G83460ZZ" ], "uniprot_id": "Q9Z0F7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "MAFLD", "glycan_involvement": "Glycosylation modulates adiponectin's anti-inflammatory effects.", "mechanism": "Higher adiponectin/leptin ratio after VV mixture supplementation is associated with reduced hepatic inflammation and steatosis.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12389231" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Leptin glycosylation influences receptor interaction and metabolic signaling.", "mechanism": "Hyperleptinemia is linked to leptin resistance and insulin resistance; VV mixture reduced leptin, suggesting improved insulin sensitivity.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12389231" }, { "confidence": "high", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "POD is a glycoprotein; glycosylation is required for stability and secretion.", "mechanism": "Upregulated during infection, promotes lignin synthesis and cell wall strengthening, limiting pathogen spread.", "protein": "Peroxidase (POD)", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "high", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "COMT is a glycoprotein; glycosylation may affect localization and activity.", "mechanism": "Upregulated in mild infection, catalyzes lignin precursor synthesis and phenolic defense compounds (e.g., chlorogenic acid).", "protein": "Caffeic acid 3-O-methyltransferase (COMT)", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "high", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "CAD is a glycoprotein; glycosylation may influence enzyme stability.", "mechanism": "Upregulated, catalyzes final step in lignin monomer synthesis, enhancing cell wall resistance.", "protein": "Cinnamyl alcohol dehydrogenase (CAD)", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "medium", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "F5H is a glycoprotein; glycosylation may affect function.", "mechanism": "Upregulated in severe infection, shifts lignin synthesis to S-type lignin, increasing wall rigidity.", "protein": "Ferulate-5-hydroxylase (F5H)", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "high", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "PPO is a glycoprotein; glycosylation is important for activity.", "mechanism": "Activated in mild infection, oxidizes phenolics to quinones, directly inhibiting pathogen growth.", "protein": "Polyphenol oxidase (PPO)", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "medium", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "SOD is a glycoprotein; glycosylation may affect stability.", "mechanism": "Upregulated in severe infection, detoxifies ROS to protect tissue from oxidative damage.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "medium", "disease": "Rust disease (Melampsora apocyni infection)", "glycan_involvement": "Catalyzes glycosylation of small molecules, not itself a glycoprotein function.", "mechanism": "Upregulated, catalyzes glycosylation of flavonoids and phenolics, enhancing solubility and storage of defense compounds.", "protein": "UDP-glycosyltransferase", "relationship_type": "protective", "source_pmcid": "PMC12389282" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "NF-\u03baB is glycosylated, which may affect nuclear translocation and stability.", "mechanism": "NF-\u03baB activation drives hepatic inflammation and cytokine production after APAP overdose; inhibition by Pristimerin is protective.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "iNOS glycosylation affects enzyme stability and localization.", "mechanism": "iNOS upregulation increases NO and peroxynitrite, contributing to oxidative/nitrosative stress and hepatocyte damage.", "protein": "iNOS", "protein_enriched": { "function": "Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumori", "gene_name": "NOS2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P35228" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "COX-II glycosylation modulates enzyme activity and secretion.", "mechanism": "COX-II induction promotes inflammatory prostaglandin synthesis, exacerbating liver injury; Pristimerin suppresses COX-II.", "protein": "COX-II", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "TNF-\u03b1 glycosylation is essential for secretion and receptor binding.", "mechanism": "TNF-\u03b1 is upregulated in APAP toxicity, driving inflammation and cell death; Pristimerin reduces TNF-\u03b1 levels.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "IL-6 glycosylation required for stability and bioactivity.", "mechanism": "IL-6 is elevated in APAP-induced liver injury, mediating inflammatory response; Pristimerin lowers IL-6.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "IL-1\u03b2 glycosylation affects secretion and activity.", "mechanism": "IL-1\u03b2 upregulation promotes hepatic inflammation and injury; Pristimerin suppresses IL-1\u03b2.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "medium", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "PI3K glycosylation may regulate membrane localization and signaling.", "mechanism": "PI3K/AKT pathway activation promotes hepatocyte survival and regeneration; APAP suppresses, Pristimerin restores PI3K signaling.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12389303" }, { "confidence": "medium", "disease": "Acetaminophen-induced acute liver injury", "glycan_involvement": "AKT glycosylation can modulate kinase activity.", "mechanism": "AKT phosphorylation supports anti-apoptotic signaling; Pristimerin increases p-AKT, counteracting APAP-induced suppression.", "protein": "AKT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Liver apoptosis", "glycan_involvement": "BCL-2 glycosylation may affect mitochondrial targeting.", "mechanism": "BCL-2 is anti-apoptotic; APAP decreases BCL-2, Pristimerin restores its expression, reducing apoptosis.", "protein": "BCL-2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Liver apoptosis", "glycan_involvement": "BAX glycosylation may influence mitochondrial translocation.", "mechanism": "BAX is pro-apoptotic; APAP increases BAX, promoting apoptosis; Pristimerin reduces BAX expression.", "protein": "BAX", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12389303" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "HK-2 glycosylation may affect stability and localization; chrysin's effect is on protein-protein interaction.", "mechanism": "Chrysin inhibits HK-2, disrupting glycolysis and inducing mitochondria-mediated apoptosis.", "protein": "Hexokinase 2 (HK-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "high", "disease": "Breast cancer (HER2+)", "glycan_involvement": "HER2 glycosylation modulates receptor activity and drug sensitivity.", "mechanism": "Chrysin enhances inhibition of HER2+ breast cancer growth when combined with pyrotinib.", "protein": "Human Epidermal Growth Factor Receptor 2 (HER2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "TLR4 glycosylation is essential for ligand recognition and signaling.", "mechanism": "Chrysin decreases TLR4 and Myd88 expression, suppressing inflammation and metastasis.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "TRAIL glycosylation affects receptor binding and apoptotic signaling.", "mechanism": "Chrysin activates TRAIL-mediated caspase activation, inducing apoptosis.", "protein": "TRAIL", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "IL-6 glycosylation influences secretion and receptor interaction.", "mechanism": "Chrysin reduces IL-6 levels, inhibiting inflammation and disease progression.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "IL-1\u03b2 glycosylation affects stability and activity.", "mechanism": "Chrysin suppresses IL-1\u03b2 production, reducing neuroinflammatory damage.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "TNF-\u03b1 glycosylation modulates receptor binding and inflammatory signaling.", "mechanism": "Chrysin lowers TNF-\u03b1, reducing inflammation and vascular dysfunction.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "COX-2 glycosylation affects enzyme activity and localization.", "mechanism": "Chrysin suppresses COX-2, reducing prostaglandin synthesis and tumor growth.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "medium", "disease": "Endometriosis", "glycan_involvement": "VEGF glycosylation is critical for receptor binding and angiogenic activity.", "mechanism": "Chrysin and related flavonoids inhibit VEGF-mediated angiogenesis.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "low", "disease": "Multiple sclerosis", "glycan_involvement": "GSK-3\u03b2 glycosylation may influence protein stability and signaling.", "mechanism": "Chrysin reduces GSK-3\u03b2 activity, modulating neuroinflammation and neurogenesis.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389306" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "AKT1 is glycosylated, affecting stability and signaling.", "mechanism": "AKT1 upregulation promotes hepatic glycogen synthesis, reducing hyperglycemia.", "protein": "AKT1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389309" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "GSK3B glycosylation modulates activity and cellular localization.", "mechanism": "GSK3B downregulation reduces gluconeogenesis and improves glucose utilization.", "protein": "GSK3B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389309" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "TNF glycosylation affects secretion and receptor binding.", "mechanism": "Elevated TNF promotes inflammation and insulin resistance.", "protein": "TNF", "relationship_type": "causal", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "IL-6 glycosylation regulates stability and activity.", "mechanism": "Increased IL-6 indicates hepatic inflammatory state in T2D.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "IL-10 glycosylation modulates anti-inflammatory function.", "mechanism": "IL-10 upregulation suppresses hepatic inflammation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "EGFR N-glycosylation affects ligand binding and signaling.", "mechanism": "EGFR signaling implicated in metabolic regulation and insulin sensitivity.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "IGF1R glycosylation modulates receptor function.", "mechanism": "IGF1R involved in insulin signaling and glucose homeostasis.", "protein": "IGF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Liver inflammation", "glycan_involvement": "PTGS2 glycosylation affects enzyme activity.", "mechanism": "PTGS2 upregulation marks inflammatory response in T2D liver.", "protein": "PTGS2 (COX-2)", "relationship_type": "biomarker", "source_pmcid": "PMC12389309" }, { "confidence": "medium", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "MMP9 glycosylation regulates secretion and activity.", "mechanism": "MMP9 elevation contributes to tissue remodeling and barrier disruption.", "protein": "MMP9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (Pu", "gene_name": "Mmp9", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P41245" }, "relationship_type": "causal", "source_pmcid": "PMC12389309" }, { "confidence": "low", "disease": "Renal dysfunction", "glycan_involvement": "KDR glycosylation modulates receptor signaling.", "mechanism": "KDR signaling involved in vascular changes in diabetic kidney.", "protein": "KDR (VEGFR2)", "relationship_type": "biomarker", "source_pmcid": "PMC12389309" }, { "confidence": "high", "disease": "Genitourinary Syndrome of Menopause (GSM)", "glycan_involvement": "Direct application of LMWHA/vLMWHA enhances ECM remodeling and mucosal glycan layer.", "mechanism": "Restores vaginal mucosal architecture, increases epithelial thickness, relieves dryness and dyspareunia.", "protein": "Hyaluronic Acid (LMWHA/vLMWHA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "HPV Infection and Cervical Lesions", "glycan_involvement": "vLMWHA fragments modulate immune response and tissue repair.", "mechanism": "Promotes viral clearance and lesion regression, increases apoptosis and p53, decreases E6/E7 expression.", "protein": "Hyaluronic Acid (vLMWHA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Pelvic Radiotherapy-induced Vaginal Atrophy", "glycan_involvement": "LMWHA supports ECM regeneration and mucosal glycan layer restoration.", "mechanism": "Accelerates tissue healing, reduces inflammation, atrophy, and fibrosis.", "protein": "Hyaluronic Acid (LMWHA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Preterm Birth (PTB)", "glycan_involvement": "Intact HMWHA shields TLRs, prevents pro-inflammatory signaling.", "mechanism": "Maintains cervical barrier integrity, prevents bacterial ascension, reduces inflammation.", "protein": "Hyaluronic Acid (HMWHA)", "relationship_type": "protective", "source_pmcid": "PMC12389360" }, { "confidence": "medium", "disease": "Threatened Miscarriage/Subchorionic Hematoma", "glycan_involvement": "HMWHA supports ECM stability and anti-inflammatory environment.", "mechanism": "Oral HMWHA supplementation accelerates hematoma resorption and symptom resolution.", "protein": "Hyaluronic Acid (HMWHA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Embryonic Developmental Defects (gut malrotation, volvulus)", "glycan_involvement": "TSG-6 is a glycoprotein that covalently modifies HA, impacting ECM structure.", "mechanism": "TSG-6 modifies HA in ECM, essential for gut looping and vascular development; deficiency leads to malrotation.", "protein": "TSG-6", "relationship_type": "causal", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Embryonic Developmental Defects (cardiac, craniofacial, limb)", "glycan_involvement": "HAS2 is a glycosyltransferase essential for HA biosynthesis.", "mechanism": "HAS2 synthesizes HMWHA; deficiency causes defects in heart, palate, limb, and craniofacial development.", "protein": "HAS2", "relationship_type": "causal", "source_pmcid": "PMC12389360" }, { "confidence": "medium", "disease": "Physiological Pregnancy", "glycan_involvement": "CD44 is a glycoprotein HA receptor mediating cell-ECM interactions.", "mechanism": "CD44-HA interaction promotes decidual stromal cell proliferation, trophoblast migration, and immunotolerance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12389360" }, { "confidence": "medium", "disease": "Primary Ovarian Insufficiency (POI)", "glycan_involvement": "PGRMC1 is a membrane glycoprotein modulated by HA.", "mechanism": "HMWHA upregulates PGRMC1, supporting progesterone signaling and ovarian function.", "protein": "PGRMC1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Bacterial Ascending Infection (Group B Streptococcus)", "glycan_involvement": "HA integrity is critical for ECM barrier function.", "mechanism": "HMWHA prevents bacterial ascension by maintaining cervical ECM; GBS hyaluronidase degrades HA, increasing infection risk.", "protein": "Hyaluronic Acid (HMWHA)", "relationship_type": "protective", "source_pmcid": "PMC12389360" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation affects albumin stability and denaturation susceptibility.", "mechanism": "Denaturation of albumin used as a model for anti-inflammatory activity; inhibition indicates anti-inflammatory potential.", "protein": "Egg albumin", "relationship_type": "biomarker", "source_pmcid": "PMC12389382" }, { "confidence": "high", "disease": "Gastric ulcer", "glycan_involvement": "O-glycosylation critical for mucin barrier function.", "mechanism": "Mucins form the gastric mucosal barrier; antioxidant and anti-inflammatory extracts protect mucins from ROS-induced degradation.", "protein": "Mucins", "relationship_type": "protective", "source_pmcid": "PMC12389382" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation modulates enzyme activity and stability.", "mechanism": "Upregulation of myeloperoxidase by viruses increases oxidative stress and inflammation.", "protein": "Myeloperoxidase", "relationship_type": "causal", "source_pmcid": "PMC12389382" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "No direct glycosylation involvement mentioned.", "mechanism": "NRF2 downregulation by viruses impairs antioxidant response, increasing inflammation.", "protein": "NRF2", "relationship_type": "protective", "source_pmcid": "PMC12389382" }, { "confidence": "medium", "disease": "Gastric ulcer", "glycan_involvement": "Glycosylation influences albumin\u2019s resistance to denaturation.", "mechanism": "Protein denaturation inhibition by extracts indicates protection against ulcer-related protein damage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389382" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "N-glycosylation regulates immunoglobulin function.", "mechanism": "Immunomodulatory effects of extracts may modulate glycoprotein-mediated immune responses.", "protein": "Immunoglobulins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389382" }, { "confidence": "high", "disease": "Gastric ulcer", "glycan_involvement": "O-glycosylation essential for mucosal protection.", "mechanism": "Extracts protect gastric mucosal glycoproteins from ROS-induced breakdown, reducing ulcer formation.", "protein": "Gastric mucosal glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12389382" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Altered glycosylation affects cell adhesion and tumor metastasis.", "mechanism": "ROS disrupt cell adhesion glycoproteins, promoting cancer progression.", "protein": "Cell adhesion glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389382" }, { "confidence": "low", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Extracts may inhibit COX activity, reducing prostaglandin-mediated inflammation.", "protein": "Prostaglandin synthase (COX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389382" }, { "confidence": "low", "disease": "Melanogenesis disorders", "glycan_involvement": "N-glycosylation required for tyrosinase activity.", "mechanism": "Extracts inhibit tyrosinase, affecting melanogenesis.", "protein": "Tyrosinase", "protein_enriched": { "function": "This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reacti", "gene_name": "TYR", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P14679" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389382" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Fc glycosylation modulates effector functions and stability.", "mechanism": "IgG antibodies are used as targeting moieties in ADCs for selective delivery of cytotoxic drugs to tumor cells.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Fc glycosylation affects ADCC and pharmacokinetics.", "mechanism": "Targets HER2-positive tumor cells for ADC-mediated cytotoxicity (e.g., T-DM1).", "protein": "Trastuzumab (anti-HER2 IgG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Lymphoma", "glycan_involvement": "Glycosylation may affect antigen recognition and ADC binding.", "mechanism": "CD30 is targeted by brentuximab vedotin ADC for selective killing of lymphoma cells.", "protein": "CD30", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Colorectal Carcinoma", "glycan_involvement": "CEA is heavily glycosylated, influencing antibody binding and tumor specificity.", "mechanism": "CEA-targeted ADCs deliver cytotoxic payloads to colorectal cancer cells.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "medium", "disease": "Colorectal Carcinoma", "glycan_involvement": "Glycosylation may modulate antigen accessibility.", "mechanism": "GCC-targeted ADCs (e.g., TAK-164) deliver DNA-alkylating payloads to tumor cells.", "protein": "Guanylyl Cyclase C (GCC)", "protein_enriched": { "function": "Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP (PubMed:11950846, PubMed:1718270, PubMed:22436048, PubMed:22521417, PubMed:23269669). Receptor for the E.coli heat-stable entero", "gene_name": "GUCY2C", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P25092" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "medium", "disease": "Solid Tumors (general)", "glycan_involvement": "Glycosylation affects ECM localization and antibody binding.", "mechanism": "ECM-targeted ADCs bind tenascin-C isoforms in tumor stroma for localized drug release.", "protein": "Tenascin-C", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Core fucosylation of Fc modulates receptor affinity and ADCC potency.", "mechanism": "Fc\u03b3RIIIa mediates ADCC upon binding to glycosylated Fc region of therapeutic antibodies.", "protein": "Fc\u03b3 Receptor IIIa (CD16a)", "relationship_type": "biomarker", "source_pmcid": "PMC12389400" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation may affect enzyme stability and localization.", "mechanism": "Lysosomal cathepsin B cleaves peptide linkers in ADCs for intracellular payload release.", "protein": "Cathepsin B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation influences receptor conformation and antibody binding.", "mechanism": "HER2 is targeted by trastuzumab-based ADCs for selective cytotoxicity.", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation affects cytokine stability and receptor interaction.", "mechanism": "Immunocytokines (antibody\u2013IL-2 conjugates) increase local cytokine concentration in tumors.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389400" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Synthesizes \u03b2-glucan polysaccharide backbone of cell wall.", "mechanism": "Targeted by echinocandins to disrupt cell wall synthesis.", "protein": "1,3-\u03b2-D-glucan synthase (FKS subunits)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Drug-resistant fungal infections", "glycan_involvement": "GPI anchor is a glycan modification essential for protein localization.", "mechanism": "Inhibited by fosmanogepix, disrupting cell wall mannoprotein assembly.", "protein": "GPI-anchored wall transfer protein 1 (GWT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Fungal biofilm-associated infections", "glycan_involvement": "Highly glycosylated, forming extracellular matrix.", "mechanism": "Major component of biofilm matrix, contributing to drug resistance.", "protein": "Mannoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389444" }, { "confidence": "medium", "disease": "Drug-resistant fungal infections", "glycan_involvement": "Glycosylation may affect stability and function.", "mechanism": "Stabilizes stress response proteins, associated with amphotericin B resistance.", "protein": "Heat-shock protein 90 (HSP90)", "relationship_type": "causal", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Coccidioidomycosis", "glycan_involvement": "Synthesizes chitin, a key glycan in fungal cell wall.", "mechanism": "Inhibited by nikkomycin Z, disrupting cell wall integrity.", "protein": "Chitin synthase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Drug-resistant fungal infections", "glycan_involvement": "Glycosylation affects membrane localization and function.", "mechanism": "Overexpression leads to azole resistance by reducing intracellular drug concentration.", "protein": "Efflux pumps (ABC transporters)", "relationship_type": "causal", "source_pmcid": "PMC12389444" }, { "confidence": "medium", "disease": "Drug-resistant fungal infections", "glycan_involvement": "Regulates glycoprotein synthesis for cell wall repair.", "mechanism": "Upregulates chitin and mannan synthesis in response to echinocandin-induced cell wall stress.", "protein": "Protein Kinase C\u2013Mitogen-Activated Protein Kinase (PKC-MAPK)", "relationship_type": "causal", "source_pmcid": "PMC12389444" }, { "confidence": "medium", "disease": "Drug-resistant fungal infections", "glycan_involvement": "Indirectly regulates glycoprotein synthesis.", "mechanism": "Activates compensatory chitin synthesis, contributing to echinocandin tolerance.", "protein": "Calcineurin", "protein_enriched": { "function": "Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription fa", "gene_name": "PPP3CC", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P48454" }, "relationship_type": "causal", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Invasive candidiasis", "glycan_involvement": "Fungal cell wall glycan released during infection.", "mechanism": "Detected in serum as a diagnostic marker for invasive candidiasis.", "protein": "Mannan", "relationship_type": "biomarker", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Invasive aspergillosis", "glycan_involvement": "Galactomannan is a glycosylated cell wall component.", "mechanism": "Galactomannan (mannoprotein glycan) detected in serum for diagnosis.", "protein": "Mannoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12389444" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "PDGFR-\u03b2 is a glycoprotein; glycosylation is required for proper folding and cell surface expression.", "mechanism": "PDGFR-\u03b2 signaling promotes hepatic stellate cell activation and fibrogenesis; inhibition reduces fibrosis.", "protein": "PDGFR-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389491" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "PDGF-BB is glycosylated, which affects its stability and receptor binding.", "mechanism": "PDGF-BB is a potent mitogen for HSCs, driving their activation and collagen production.", "protein": "PDGF-BB", "relationship_type": "causal", "source_pmcid": "PMC12389491" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen I is glycosylated, which influences fibril formation and stability.", "mechanism": "Collagen I is the main ECM protein deposited during fibrosis; its expression reflects fibrotic severity.", "protein": "Collagen I", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "Col4a1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02463" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TGF-\u03b21 is glycosylated, affecting secretion and receptor interaction.", "mechanism": "TGF-\u03b21 promotes HSC activation and ECM production.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "IL-6 is glycosylated, which modulates its stability and activity.", "mechanism": "IL-6 is elevated in fibrotic and cirrhotic livers, reflecting inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "IL-1\u03b2 is glycosylated, influencing secretion and activity.", "mechanism": "IL-1\u03b2 promotes HSC survival and inflammatory signaling.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting its secretion and receptor binding.", "mechanism": "TNF-\u03b1 promotes inflammation and HSC activation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "LOX is glycosylated, which is important for its secretion and enzymatic activity.", "mechanism": "LOX crosslinks collagen, stabilizing fibrotic ECM.", "protein": "LOX", "protein_enriched": { "function": "Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:26838787). Regulator of Ras expression. May play a role i", "gene_name": "LOX", "glycan_count": 32, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G23863VK", "G31852PQ", "G37881RL", "G48414YA", "G60967DT", "G62765YT", "G66538GV", "G80920RR", "G83460ZZ", "G92050GC", "G43417UB", "G49108TO", "G13694XX", "G62461SM", "G02815KT", "G06330RB", "G22310AV", "G25418HZ", "G41247ZX", "G45504EY", "G46503DX", "G64394MX", "G80223IX", "G84452RH", "G90659AW", "G99668VU", "G14943SF", "G26915XM", "G27058EU", "G45395BF", "G63543FL" ], "uniprot_id": "P28300" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389491" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "CD163 is a heavily glycosylated scavenger receptor; glycosylation affects ligand binding.", "mechanism": "CD163 marks M2 macrophages, which are associated with anti-inflammatory and tissue repair responses in fibrosis.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389491" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation required for PDGFR-\u03b2 function.", "mechanism": "PDGFR-\u03b2 signaling is implicated in tumor stroma formation and progression.", "protein": "PDGFR-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389491" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects enzyme stability and localization.", "mechanism": "AChE breaks down acetylcholine; inhibition increases synaptic ACh, improving cognition.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389534" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates activity and tissue distribution.", "mechanism": "BChE regulates acetylcholine levels, especially as AChE declines in AD; inhibition increases ACh.", "protein": "Butyrylcholinesterase (BChE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389534" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences APP processing and amyloid-\u03b2 generation.", "mechanism": "APP is cleaved to produce amyloid-\u03b2, which aggregates into plaques.", "protein": "Amyloid-\u03b2 precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12389534" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects BACE1 trafficking and activity.", "mechanism": "BACE1 cleaves APP, initiating amyloid-\u03b2 production; inhibition reduces plaque formation.", "protein": "BACE1 (Beta-secretase 1)", "protein_enriched": { "function": "Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generatio", "gene_name": "BACE1", "glycan_count": 36, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G80920RR", "G05724UK", "G06110VR", "G12398HZ", "G14023ZV", "G14669DU", "G15065YV", "G17689DH", "G21112KH", "G22310AV", "G22768VO", "G23863VK", "G25520XG", "G29880MM", "G39188ZX", "G44444MB", "G46687AB", "G49874UX", "G55220VL", "G60230HH", "G63889NK", "G64527OM", "G70101JE", "G70375MX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G80966KZ", "G84452RH", "G87618BG", "G90093AU", "G91636VS", "G93993PD", "G94854LT" ], "uniprot_id": "P56817" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389534" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for TLR4 ligand recognition and signaling.", "mechanism": "A\u03b2 interacts with TLR4, triggering inflammatory cascades and NLRP3 activation.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC12389534" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may regulate assembly and activation.", "mechanism": "Activated by A\u03b2-TLR4 signaling, leading to IL-1\u03b2 and TNF-\u03b1 release.", "protein": "NLRP3 inflammasome", "relationship_type": "causal", "source_pmcid": "PMC12389534" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation can affect nuclear translocation and activity.", "mechanism": "NF-\u03baB upregulation reflects inflammatory response in AD brain.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389534" }, { "confidence": "low", "disease": "Neuronal apoptosis", "glycan_involvement": "Glycosylation may influence activation and substrate specificity.", "mechanism": "Caspase-1 activation leads to pyroptosis and neurodegeneration.", "protein": "Caspase-1", "relationship_type": "biomarker", "source_pmcid": "PMC12389534" }, { "confidence": "medium", "disease": "Neuronal apoptosis", "glycan_involvement": "Glycosylation may affect anti-apoptotic function.", "mechanism": "Bcl-2 suppresses apoptosis; upregulation is neuroprotective in AD.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12389534" }, { "confidence": "medium", "disease": "Neuronal apoptosis", "glycan_involvement": "Glycosylation may regulate pro-apoptotic activity.", "mechanism": "BAX promotes apoptosis; overexpression contributes to neuronal loss in AD.", "protein": "BAX", "relationship_type": "causal", "source_pmcid": "PMC12389534" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PD-1 is glycosylated, which affects ligand binding and immune regulation.", "mechanism": "PD-1 suppresses T-cell activity; aptamer blockade restores anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PD-L1 glycosylation modulates stability and immune evasion.", "mechanism": "PD-L1 on tumor cells binds PD-1, suppressing immune response; aptamer inhibition restores T-cell function.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "CTLA-4 glycosylation affects surface expression and ligand binding.", "mechanism": "CTLA-4 inhibits T-cell activation; aptamer blockade enhances anti-tumor immunity.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "TIM-3 and galectin-9 interactions are glycan-dependent.", "mechanism": "TIM-3/galectin-9 interaction induces T-cell exhaustion; aptamer disrupts this, restoring T-cell function.", "protein": "TIM-3", "protein_enriched": { "function": "Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may b", "gene_name": "HAVCR2", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29931IJ", "G31916IQ", "G43417UB", "G47681UP", "G49108TO" ], "uniprot_id": "Q8TDQ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "LAG-3 glycosylation influences ligand binding.", "mechanism": "LAG-3 binds MHC II, suppressing T-cell activation; aptamer blockade reverses immune suppression.", "protein": "LAG-3", "protein_enriched": { "function": "Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as F", "gene_name": "LAG3", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G22768VO" ], "uniprot_id": "P18627" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "TIGIT and CD155/CD112 are glycoproteins; glycosylation affects receptor-ligand interaction.", "mechanism": "TIGIT inhibits T/NK cell activation via CD155/CD112; aptamer blocks this, boosting immunity.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "VISTA is glycosylated, impacting its inhibitory function.", "mechanism": "VISTA inhibits T-cell activation; aptamer blockade restores immune response.", "protein": "VISTA", "protein_enriched": { "function": "Cell surface glycoprotein involved in various biological processes including angiogenesis, immune response modulation, and tissue remodeling and repair. Participates in pericyte proliferation through ", "gene_name": "CD248", "glycan_count": 5, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57317CE", "G49108TO" ], "uniprot_id": "Q9HCU0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "B7-H3 glycosylation modulates immune interactions.", "mechanism": "B7-H3 inhibits T-cell activation; aptamer disrupts immune suppression.", "protein": "B7-H3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Galectin-9 is a glycan-binding protein; interaction is glycan-dependent.", "mechanism": "Galectin-9 binds TIM-3, inducing T-cell exhaustion and immune evasion.", "protein": "Galectin-9", "protein_enriched": { "function": "Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocy", "gene_name": "LGALS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00182" }, "relationship_type": "causal", "source_pmcid": "PMC12389541" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "EGFR glycosylation affects receptor function and drug targeting.", "mechanism": "EGFR overexpression promotes tumor growth; aptamer targeting enables drug delivery.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389541" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects CD105 stability and cell adhesion.", "mechanism": "MSC surface marker involved in osteogenic differentiation; GO/PLLA scaffolds enhance MSC-mediated bone regeneration.", "protein": "CD105 (Endoglin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "high", "disease": "Bone fracture", "glycan_involvement": "N-glycosylation modulates enzymatic activity and cell migration.", "mechanism": "MSC marker; GO/PLLA scaffolds promote MSC proliferation and differentiation for bone repair.", "protein": "CD73 (5'-nucleotidase ecto)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Cartilage injury", "glycan_involvement": "Glycosylation influences cell\u2013matrix interactions.", "mechanism": "MSC marker; GO-based scaffolds support chondrogenic differentiation for cartilage regeneration.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "high", "disease": "Transplant rejection", "glycan_involvement": "Glycosylation critical for antigen presentation.", "mechanism": "MSC negative for HLA-DR; low immunogenicity reduces risk of rejection in regenerative therapies.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Inflammatory disease", "glycan_involvement": "O-glycosylation modulates filament assembly.", "mechanism": "Upregulated during EMT in response to GO; associated with increased cell migration and cytokine secretion.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Skin wound", "glycan_involvement": "N-glycosylation affects secretion and activity.", "mechanism": "GO/PLLA scaffolds upregulate MMPs via Wnt/\u03b2-catenin pathway, promoting ECM remodeling and wound healing.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "high", "disease": "Bone fracture", "glycan_involvement": "Glycosylation required for BMP secretion and receptor binding.", "mechanism": "GO enhances BMP-mediated osteogenesis in MSCs for bone repair.", "protein": "BMPs (Bone Morphogenetic Proteins)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Peripheral nerve injury", "glycan_involvement": "Glycosylation stabilizes enzyme structure.", "mechanism": "GO upregulates MnSOD, reducing oxidative stress and supporting nerve regeneration.", "protein": "MnSOD (Manganese Superoxide Dismutase)", "relationship_type": "protective", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation modulates cell adhesion.", "mechanism": "MSC negative for CD34; used to distinguish MSCs from hematopoietic cells in immune therapies.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389577" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycan moieties enhance solubility and targeting.", "mechanism": "Water-soluble glycofullerene shows no cytotoxicity and potential for drug delivery in cancer therapy.", "protein": "Glycofullerene", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389577" }, { "confidence": "high", "disease": "Respiratory viral infections (RSV, adenovirus, IAV, parainfluenza)", "glycan_involvement": "Lf glycosylation enhances its binding to viral and host glycan structures.", "mechanism": "Lf inhibits viral entry and replication via binding to viral glycoproteins and host cell surface components.", "protein": "Lactoferrin (Lf)", "relationship_type": "protective", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "SARS-CoV, SARS-CoV-2, HCoV-OC43, HCoV-NL63, HCoV-229E infections", "glycan_involvement": "bLf glycosylation is critical for interaction with viral and host glycans.", "mechanism": "bLf binds viral spike proteins and host cell heparan sulfate proteoglycans, blocking viral entry.", "protein": "Bovine Lactoferrin (bLf)", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 28, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00395TQ", "G05724UK", "G06110VR", "G14669DU", "G22768VO", "G31685JQ", "G39188ZX", "G40702WU", "G55220VL", "G60230HH", "G64527OM", "G68668TB", "G70101JE", "G74724QE", "G80966KZ", "G82348BZ", "G22573RC", "G23432EQ", "G29880MM", "G33609NS", "G60145BJ", "G63628AV", "G65343UJ", "G81295CK", "G23453IV", "G37664BH", "G89864BN", "G91704UR" ], "uniprot_id": "P24627" }, "relationship_type": "protective", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "Common Cold, Pneumonia, Bronchiolitis, Neuroinvasive Disease", "glycan_involvement": "Spike protein is heavily glycosylated, which modulates receptor binding and immune evasion.", "mechanism": "Spike protein mediates viral entry via binding to hAPN/CD13 and membrane fusion.", "protein": "HCoV-229E Spike Protein (S)", "protein_enriched": { "function": "S1 region attaches the virion to the cell membrane by interacting with host ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S g", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15423" }, "relationship_type": "causal", "source_pmcid": "PMC12389581" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Spike glycosylation may influence tropism and immune response.", "mechanism": "HCoV-229E infection associated with asthma exacerbation.", "protein": "HCoV-229E Spike Protein (S)", "protein_enriched": { "function": "S1 region attaches the virion to the cell membrane by interacting with host ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S g", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15423" }, "relationship_type": "causal/trigger", "source_pmcid": "PMC12389581" }, { "confidence": "low", "disease": "Kawasaki Disease", "glycan_involvement": "Spike glycosylation may affect immune activation.", "mechanism": "Possible involvement of HCoV-229E in Kawasaki disease pathogenesis.", "protein": "HCoV-229E Spike Protein (S)", "protein_enriched": { "function": "S1 region attaches the virion to the cell membrane by interacting with host ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S g", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15423" }, "relationship_type": "hypothesized causal", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "Influenza A Virus Infection", "glycan_involvement": "HA glycosylation modulates receptor binding and antigenicity.", "mechanism": "HA mediates viral entry via sialic acid binding and membrane fusion.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "HCoV-229E Infection", "glycan_involvement": "Targeting glycosylated spike regions; glycan shield may affect binding.", "mechanism": "Peptidomimetics bind spike protein, inhibit conformational changes required for membrane fusion and entry.", "protein": "Lactoferrin-derived peptidomimetics (SK(N-Me)HS, S N KHS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "HCoV-229E Infection, Neuroinvasive Disease", "glycan_involvement": "hAPN glycosylation is essential for spike binding.", "mechanism": "hAPN/CD13 acts as the cellular receptor for HCoV-229E, facilitating entry into respiratory and neural cells.", "protein": "Human Aminopeptidase N (hAPN/CD13)", "relationship_type": "causal", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "Influenza A Virus Infection", "glycan_involvement": "Peptide interaction with glycosylated HA domains.", "mechanism": "Peptides bind HA, inhibit hemagglutination and viral infection.", "protein": "Lactoferrin-derived peptides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "Immunocompromised Host Infection", "glycan_involvement": "Glycosylation may enhance immune evasion and pathogenicity.", "mechanism": "Spike protein enables severe infection in immunocompromised individuals.", "protein": "HCoV-229E Spike Protein (S)", "protein_enriched": { "function": "S1 region attaches the virion to the cell membrane by interacting with host ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S g", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P15423" }, "relationship_type": "causal", "source_pmcid": "PMC12389581" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects receptor localization and ligand binding.", "mechanism": "EGCG binds directly to the receptor, modulating cell adhesion and signaling, inhibiting tumor progression.", "protein": "67 kDa laminin receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation regulates GRP78 stability and function.", "mechanism": "EGCG interacts with GRP78, affecting protein folding and stress response in tumor cells.", "protein": "GRP78 (BiP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and activation.", "mechanism": "EGCG antagonizes EGFR signaling, inhibiting cell proliferation and angiogenesis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation required for IGF1R cell surface expression.", "mechanism": "EGCG inhibits IGF1R signaling, reducing tumor growth.", "protein": "IGF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "N-glycosylation essential for VEGFR2 function.", "mechanism": "EGCG inhibits VEGFR2, suppressing angiogenesis.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "N-glycosylation affects MET activation.", "mechanism": "EGCG disrupts MET signaling, inhibiting metastasis.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "EGCG inhibits MMP-2 activity, reducing tumor invasion.", "protein": "Matrix metalloproteinase-2 (MMP-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation regulate APP processing.", "mechanism": "EGCG promotes non-toxic sAPP-\u03b1 secretion and inhibits \u03b2-amyloid fibril formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "protective", "source_pmcid": "PMC12389627" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation affects COX-2 stability.", "mechanism": "EGCG suppresses COX-2 expression, reducing inflammation.", "protein": "Cyclooxygenase-2 (COX-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "EGCG inhibits MMP-9, limiting tumor invasion and metastasis.", "protein": "Matrix metalloproteinase-9 (MMP-9)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389627" }, { "confidence": "high", "disease": "Multidrug resistance in cancer", "glycan_involvement": "N-glycosylation affects protein folding and membrane localization, impacting efflux function.", "mechanism": "Efflux of chemotherapeutic drugs from cancer cells reduces drug accumulation and efficacy.", "protein": "P-glycoprotein (ABCB1/MDR1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "high", "disease": "Multidrug resistance in cancer", "glycan_involvement": "N-glycosylation required for proper folding and trafficking.", "mechanism": "Efflux of anticancer drugs limits intracellular drug concentration.", "protein": "Breast Cancer Resistance Protein (BCRP/ABCG2)", "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Reduced drug efficacy", "glycan_involvement": "N-glycosylation modulates transporter stability and function.", "mechanism": "Efflux of drugs from enterocytes decreases oral bioavailability.", "protein": "Multidrug Resistance-associated Protein 2 (MRP2/ABCC2)", "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "high", "disease": "Drug\u2013drug interactions", "glycan_involvement": "Glycation (non-enzymatic glycan modification) alters binding properties and structure.", "mechanism": "Competition for binding sites alters free drug levels and pharmacokinetics.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "biomarker", "source_pmcid": "PMC12389637" }, { "confidence": "high", "disease": "Hyperglycemia-induced protein dysfunction", "glycan_involvement": "Non-enzymatic glycation of lysine residues disrupts normal glycoprotein function.", "mechanism": "Glycation leads to \u03b2-cross-linked structures and functional deficiency.", "protein": "Human Serum Albumin (HSA)", "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Impaired immune response", "glycan_involvement": "N-glycosylation affects ligand binding and clearance.", "mechanism": "Binding to drugs and proteases modulates immune and pharmacokinetic responses.", "protein": "Alpha-2-macroglobulin (A2M)", "relationship_type": "biomarker", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Hepatic drug metabolism disorders", "glycan_involvement": "N-glycosylation influences enzyme stability and localization.", "mechanism": "Altered enzyme activity affects drug biotransformation and clearance.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Drug-induced nephrotoxicity", "glycan_involvement": "N-glycosylation required for membrane expression and function.", "mechanism": "Transport of nephrotoxic drugs into renal cells increases toxicity risk.", "protein": "Organic Anion Transporter 1 (OAT1/SLC22A6)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Renal drug excretion disorders", "glycan_involvement": "N-glycosylation modulates transporter activity.", "mechanism": "Impaired transporter function reduces renal clearance of drugs.", "protein": "Organic Anion Transporter 3 (OAT3/SLC22A8)", "protein_enriched": { "function": "Uniport that mediates the transport of neutral amino acids such as L-leucine, L-isoleucine, L-valine, and L-phenylalanine (PubMed:12930836). The transport activity is sodium ions-independent, electron", "gene_name": "SLC43A1", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O75387" }, "relationship_type": "causal", "source_pmcid": "PMC12389637" }, { "confidence": "medium", "disease": "Altered drug pharmacokinetics", "glycan_involvement": "Highly glycosylated; glycan heterogeneity influences drug binding.", "mechanism": "Binding to basic drugs affects distribution and free drug concentration.", "protein": "Alpha-1-acid glycoprotein (AGP/ORM1)", "relationship_type": "biomarker", "source_pmcid": "PMC12389637" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein is essential for viral infectivity and immune evasion.", "mechanism": "Benzimidazole\u2013pyrimidine hybrids inhibit the receptor binding domain of spike glycoprotein, blocking viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect CDK4/6 stability and localization.", "mechanism": "Abemaciclib (benzimidazole\u2013pyrimidine hybrid) inhibits CDK4/6, blocking cell cycle progression in breast cancer cells.", "protein": "CDK4/6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "Glycosylation can modulate kinase activity and cell signaling.", "mechanism": "Hybrids inhibit Aurora B kinase, leading to cell cycle arrest and apoptosis in leukemia cells.", "protein": "Aurora B kinase", "protein_enriched": { "function": "Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722", "gene_name": "AURKB", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G59924QI", "G49108TO" ], "uniprot_id": "Q96GD4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation is critical for VEGFR2 function and ligand binding.", "mechanism": "Hybrids inhibit VEGFR2, suppressing angiogenesis and tumor growth.", "protein": "VEGFR2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and emb", "gene_name": "KDR", "glycan_count": 8, "glycosylation_sites_count": 18, "glytoucan_ids": [ "G49108TO", "G01650EU", "G31852PQ", "G59626AS", "G43417UB", "G27058EU", "G62765YT", "G80920RR" ], "uniprot_id": "P35968" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation affects JAK3 receptor interactions.", "mechanism": "Hybrids inhibit JAK3, reducing cytokine signaling and inflammation.", "protein": "JAK3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "medium", "disease": "Inflammatory diseases", "glycan_involvement": "Glycosylation modulates COX-1 activity and membrane localization.", "mechanism": "Hybrids inhibit COX-1, decreasing prostaglandin synthesis and inflammation.", "protein": "COX-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "N-glycosylation regulates Lck membrane targeting.", "mechanism": "Hybrids inhibit Lck, blocking T-cell activation and IL-2 release.", "protein": "Lck", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may affect hTERT nuclear localization.", "mechanism": "Hybrids repress hTERT expression, limiting telomerase activity and cancer cell immortality.", "protein": "hTERT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "Fungal infections", "glycan_involvement": "Glycosylation influences \u03b2-tubulin stability and drug binding.", "mechanism": "Hybrids bind \u03b2-tubulin, disrupting microtubule assembly in fungi.", "protein": "\u03b2-tubulin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "medium", "disease": "Bacterial infections", "glycan_involvement": "Glycosylation may affect gyrase structure and drug sensitivity.", "mechanism": "Hybrids interact with gyrase, inhibiting bacterial DNA replication.", "protein": "Gyrase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389660" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for P-gp folding, trafficking, and function.", "mechanism": "P-gp limits oral absorption of ivermectin, affecting its plasma and tissue levels relevant for antiviral efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "Adverse drug reactions (e.g., bleeding)", "glycan_involvement": "Glycosylation modulates ABCB1 surface expression and drug transport.", "mechanism": "ABCB1 polymorphisms alter P-gp activity, affecting drug exposure and risk of adverse events (e.g., increased rivaroxaban Cmax and bleeding risk).", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ABCB1 function and drug efflux.", "mechanism": "Genetic variability in ABCB1 impacts ivermectin pharmacokinetics, influencing efficacy in COVID-19 repurposing.", "protein": "ABCB1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "Filariasis", "glycan_involvement": "Glycosylation required for P-gp activity.", "mechanism": "P-gp-mediated efflux affects ivermectin bioavailability in filariasis treatment.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "Thyroid cancer", "glycan_involvement": "Not applicable (CYP3A4 is not a glycoprotein).", "mechanism": "CYP3A4*1G variant reduces lenvatinib exposure in thyroid cancer patients.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389682" }, { "confidence": "low", "disease": "Thyroid cancer", "glycan_involvement": "Glycosylation influences ABCB1 function.", "mechanism": "ABCB1 polymorphisms may affect drug disposition in cancer therapy.", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "Adverse drug reactions (e.g., bleeding)", "glycan_involvement": "Glycosylation status affects P-gp stability and activity.", "mechanism": "Altered P-gp activity due to genetic or disease states can cause unpredictable drug exposure and adverse events.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "Filariasis", "glycan_involvement": "Glycosylation modulates ABCB1 function.", "mechanism": "ABCB1 genetic variability influences ivermectin pharmacokinetics in filariasis treatment.", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for P-gp function; altered glycosylation may affect drug absorption.", "mechanism": "Formulations inhibiting P-gp may enhance ivermectin bioavailability, potentially improving antiviral efficacy.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "protective", "source_pmcid": "PMC12389682" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ABCB1-mediated drug transport.", "mechanism": "ABCB1 polymorphisms may predict response to ivermectin in COVID-19 repurposing.", "protein": "ABCB1", "relationship_type": "biomarker", "source_pmcid": "PMC12389682" }, { "confidence": "high", "disease": "Hypersensitivity reactions", "glycan_involvement": "Glycosylated epitopes recognized by immune system", "mechanism": "IgE-mediated allergic response via glycoprotein epitopes", "protein": "Echinacea purpurea glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "medium", "disease": "Anaphylactoid reactions", "glycan_involvement": "Beta-glucan structure triggers immune response", "mechanism": "Immune activation by fungal glycoproteins/polysaccharides", "protein": "Ganoderma lucidum beta-glucans", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "high", "disease": "Flagellate dermatitis", "glycan_involvement": "Glycosylated proteins act as allergens", "mechanism": "Dermatological reaction to glycoprotein ingestion/contact", "protein": "Lentinula edodes glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "high", "disease": "Anaphylaxis", "glycan_involvement": "Lectin glycosylation enhances immunogenicity", "mechanism": "Lectin glycoproteins induce IgE-mediated systemic reactions", "protein": "Viscum album lectins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "high", "disease": "Hypersensitivity reactions", "glycan_involvement": "Glycosylation patterns recognized by immune cells", "mechanism": "Bee-derived glycoproteins provoke allergic responses", "protein": "Propolis glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "medium", "disease": "Hypereosinophilia", "glycan_involvement": "Polysaccharide glycan chains activate eosinophils", "mechanism": "Immune stimulation by plant polysaccharide glycoproteins", "protein": "Astragalus membranaceus polysaccharides", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Glycoprotein structure may affect hepatic metabolism", "mechanism": "Possible immune-mediated liver injury", "protein": "Silybum marianum glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "medium", "disease": "Acute hepatitis", "glycan_involvement": "Glycosylation may affect bioavailability/toxicity", "mechanism": "High-dose green tea glycoproteins induce liver injury", "protein": "Camellia sinensis glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "low", "disease": "Hepatotoxicity", "glycan_involvement": "Glycosylation may modulate immune response", "mechanism": "Plant glycoproteins implicated in liver injury", "protein": "Pelargonium sidoides glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "low", "disease": "Drug-induced autoimmune hepatitis", "glycan_involvement": "Glycan structures may act as autoantigens", "mechanism": "Autoimmune liver injury possibly triggered by glycoproteins", "protein": "Salvia miltiorrhiza glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12389708" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects P-glycoprotein localization and function at the BBB.", "mechanism": "P-glycoprotein at the blood-brain barrier limits donepezil penetration into the brain, affecting drug efficacy in AD.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates acetylcholinesterase stability and activity.", "mechanism": "Donepezil inhibits acetylcholinesterase, increasing acetylcholine levels and improving cognition in AD.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation regulates P-glycoprotein trafficking at the BBB.", "mechanism": "P-glycoprotein restricts CNS drug delivery, influencing donepezil efficacy in vascular dementia.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "medium", "disease": "Vascular dementia", "glycan_involvement": "Glycosylation impacts enzyme activity and drug interaction.", "mechanism": "Donepezil-mediated inhibition of acetylcholinesterase improves cognitive function in vascular dementia.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation influences P-glycoprotein function at the BBB.", "mechanism": "P-glycoprotein may limit CNS drug access, affecting donepezil's potential benefit in Parkinson's disease.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "low", "disease": "Autism spectrum disorder", "glycan_involvement": "Glycosylation may affect acetylcholinesterase activity and drug response.", "mechanism": "Donepezil targets acetylcholinesterase to modulate cholinergic signaling in autism spectrum disorder.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "low", "disease": "Traumatic brain injury", "glycan_involvement": "Glycosylation may modulate enzyme activity in injury states.", "mechanism": "Donepezil inhibits acetylcholinesterase to improve cognition post-TBI.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "low", "disease": "Post-stroke cognitive impairment", "glycan_involvement": "Glycosylation may affect enzyme stability and drug efficacy.", "mechanism": "Donepezil inhibits acetylcholinesterase to enhance cognitive recovery after stroke.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "low", "disease": "Down syndrome", "glycan_involvement": "Glycosylation status may influence enzyme activity and drug response.", "mechanism": "Donepezil inhibition of acetylcholinesterase was not effective in Down syndrome clinical trials.", "protein": "Acetylcholinesterase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389716" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates P-glycoprotein function and drug transport.", "mechanism": "P-glycoprotein expression at the BBB is a determinant of CNS drug delivery in AD.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389716" }, { "confidence": "high", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "N-glycosylation of NA is essential for proper folding, tetramerization, and immunogenicity.", "mechanism": "NA is targeted by vaccine-induced antibodies, which inhibit viral release and spread.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "Glycosylation ensures native conformation and antigenicity of recombinant NA.", "mechanism": "Anti-NA immune response reduces viral replication, shedding, and tissue damage in pigs.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12389839" }, { "confidence": "medium", "disease": "Influenza (general)", "glycan_involvement": "Mammalian-like glycosylation (CHO cells) enhances immunogenicity and stability.", "mechanism": "NA is a conserved antigen with lower mutation rates, making it suitable for universal vaccine strategies.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "Glycosylation affects antigenic drift and vaccine efficacy.", "mechanism": "HA is the primary antigen in commercial vaccines, inducing virus-binding antibodies.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389839" }, { "confidence": "medium", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "Glycosylation status influences antibody recognition.", "mechanism": "NA-specific IgG titers serve as a biomarker for vaccine-induced protection.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "Glycosylation required for enzymatic activity and tetramer formation.", "mechanism": "NA enzymatic activity facilitates viral release by cleaving sialic acids, completing infection cycle.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Influenza (general)", "glycan_involvement": "Glycosylation sites modulate antigenicity and immune evasion.", "mechanism": "HA mediates viral entry via sialic acid binding; antigenic drift leads to immune escape.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12389839" }, { "confidence": "medium", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "Native glycosylation supports correct folding and immunogenicity.", "mechanism": "Tetrameric NA induces broader cross-protection than HA, especially against heterologous strains.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12389839" }, { "confidence": "medium", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "CHO cell glycosylation mimics native viral glycoprotein structure.", "mechanism": "CHO-expressed NA with mammalian glycosylation elicits strong immune responses in pigs.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Swine Influenza A Virus Infection (SIV)", "glycan_involvement": "N-glycosylation critical for antigenicity and vaccine efficacy.", "mechanism": "NA-specific immunity attenuates clinical symptoms and histopathological damage.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12389839" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Antigenic drift partly driven by glycosylation changes on HA, affecting immune recognition.", "mechanism": "HA mediates viral entry via receptor binding; antibodies against HA head are strain-specific, while stem-targeted antibodies are broadly protective.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "NA glycosylation affects antigenicity and immune response.", "mechanism": "NA cleaves sialic acid to release progeny viruses; anti-NA antibodies block viral release and induce broad protection.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "high", "disease": "Pandemic Influenza", "glycan_involvement": "Glycosylation sites on HA contribute to antigenic drift and immune escape.", "mechanism": "HA antigenic shift/drift leads to emergence of new pandemic strains.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390046" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "No direct glycosylation involvement mentioned for M2e.", "mechanism": "M2e domain is highly conserved; antibodies against M2e provide cross-protective immunity via ADCC.", "protein": "Matrix protein 2 (M2)", "protein_enriched": { "function": "Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis.", "gene_name": "M", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P06821" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "No direct glycosylation involvement mentioned.", "mechanism": "NP contains conserved T-cell epitopes; induces cross-protective cytotoxic T-cell responses.", "protein": "Nucleoprotein (NP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "No direct glycosylation involvement mentioned.", "mechanism": "M1 contains conserved T-cell epitopes; induces cross-protective immunity.", "protein": "Matrix protein 1 (M1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "medium", "disease": "Severe Influenza", "glycan_involvement": "Glycosylation modulates HA antigenicity and immune evasion.", "mechanism": "HA sequence variation and glycosylation status correlate with severity and immune escape.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390046" }, { "confidence": "medium", "disease": "Pandemic Influenza", "glycan_involvement": "NA glycosylation affects antibody recognition and breadth.", "mechanism": "Anti-NA antibodies provide cross-protection against pandemic strains.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "protective", "source_pmcid": "PMC12390046" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Changes in N-glycosylation sites drive antigenic drift.", "mechanism": "HA glycosylation patterns are used to track antigenic drift and vaccine strain selection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390046" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation shields HA stem, influencing immunogenicity.", "mechanism": "Universal vaccine strategies focus immune response on conserved HA stem, overcoming glycan-mediated immune subdominance.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390046" }, { "confidence": "high", "disease": "CCDS", "glycan_involvement": "A\u03b2 is derived from glycosylated APP; glycosylation affects APP processing and A\u03b2 aggregation.", "mechanism": "Extracellular deposition of A\u03b2 (especially A\u03b2-42) forms plaques, correlating with cognitive decline and neuronal loss.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390195" }, { "confidence": "high", "disease": "CCDS", "glycan_involvement": "N-glycosylation of APP modulates its trafficking and cleavage.", "mechanism": "APP cleavage by \u03b2- and \u03b3-secretases produces A\u03b2 peptides; altered processing leads to pathogenic A\u03b2 accumulation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "O-glycosylation may regulate tau aggregation; not fully established in dogs.", "mechanism": "Hyperphosphorylation (and possibly glycosylation) of tau leads to neurofibrillary tangles and neuronal dysfunction.", "protein": "Tau protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390195" }, { "confidence": "high", "disease": "CCDS", "glycan_involvement": "NFL is glycosylated; glycosylation may affect stability and release.", "mechanism": "Elevated plasma NFL reflects axonal degeneration and correlates with disease severity.", "protein": "Neurofilament light chain (NFL)", "relationship_type": "biomarker", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "GFAP is glycosylated; glycosylation may affect filament assembly.", "mechanism": "GFAP increases after astrocytic damage/inflammation; proposed as neurodegeneration marker.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "RBP4 is N-glycosylated, affecting secretion and stability.", "mechanism": "Reduced plasma RBP4 in CCDS dogs; may reflect altered retinoid metabolism.", "protein": "Retinol-binding protein 4 (RBP4)", "protein_enriched": { "function": "Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, l", "gene_name": "SORD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G49108TO" ], "uniprot_id": "Q00796" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "CXCL10 is glycosylated, influencing chemokine activity.", "mechanism": "Lower plasma CXCL10 in CCDS; may indicate altered neuroinflammation.", "protein": "C-X-C motif chemokine ligand 10 (CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "NOX4 is glycosylated, affecting membrane localization.", "mechanism": "Decreased NOX4 in CCDS; may relate to oxidative stress regulation.", "protein": "NADPH oxidase 4 (NOX4)", "relationship_type": "biomarker", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "Glycosylation modulates enzyme activity and localization.", "mechanism": "Increased acetylcholinesterase activity leads to cholinergic deficit and cognitive decline.", "protein": "Acetylcholinesterase", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390195" }, { "confidence": "medium", "disease": "CCDS", "glycan_involvement": "Glycosylation affects enzyme stability and activity.", "mechanism": "Elevated activity increases dopamine breakdown and free radical production.", "protein": "Monoamine oxidase B", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390195" }, { "confidence": "high", "disease": "Endothelitis", "glycan_involvement": "Spike protein's glycosylation (mannose-rich) facilitates complement lectin pathway activation.", "mechanism": "Spike protein induces endothelial cell activation and inflammation via ACE2/C3aR binding and NF-\u03baB signaling.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "high", "disease": "Vasculitis", "glycan_involvement": "Glycosylation enables complement activation and immune recognition.", "mechanism": "Systemic spike protein expression leads to immune-mediated vascular inflammation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "high", "disease": "Myopericarditis", "glycan_involvement": "Glycosylated spike protein enhances immune cell recruitment.", "mechanism": "Spike protein expression in cardiac endothelial cells triggers local inflammation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "medium", "disease": "Nephrotic Syndrome", "glycan_involvement": "Glycosylation may facilitate complement activation in renal microvasculature.", "mechanism": "Spike protein induces glomerular endothelial inflammation, leading to proteinuria.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Glycosylation promotes immune-mediated injury.", "mechanism": "Spike protein expression in hepatic sinusoidal endothelium causes hepatocyte dysfunction.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "high", "disease": "Multisystem Inflammatory Response Syndrome (MIS)", "glycan_involvement": "Glycosylation enables broad complement activation.", "mechanism": "Systemic spike protein expression triggers widespread endothelial inflammation.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). 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"Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "high", "disease": "Post-Vaccination Syndrome (PVS)", "glycan_involvement": "MHC I glycosylation affects peptide presentation and immune recognition.", "mechanism": "Spike peptides presented on MHC I trigger cytotoxic T cell attack on endothelial cells.", "protein": "MHC Class I", "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "medium", "disease": "Endothelitis", "glycan_involvement": "Glycosylation maintains spike protein stability and immunogenicity in exosomes.", "mechanism": "Exosome-associated spike protein circulates and induces endothelial inflammation.", "protein": "Exosomal Spike Protein", "relationship_type": "causal", "source_pmcid": "PMC12390297" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation stabilizes GM-CSF and modulates its receptor binding.", "mechanism": "oHSV expressing GM-CSF enhances local immune response and APC activation, improving anti-tumor immunity.", "protein": "GM-CSF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation required for secretion and bioactivity.", "mechanism": "oHSV-IL-12 induces IFN-\u03b3 production and T cell activation, enhancing anti-tumor immunity.", "protein": "IL-12", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "N-glycosylation modulates anti-angiogenic activity.", "mechanism": "oHSV-TSP-1 inhibits tumor angiogenesis, reducing tumor growth.", "protein": "Thrombospondin-1 (TSP-1)", "protein_enriched": { "function": "Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:15014436, PubMed:18285447, PubMed:2430973, PubMed:6489349). 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"G57776ZS", "G59324HL", "G60834IK", "G64409MC", "G65000LJ", "G70223PD", "G70232NH", "G72667IM", "G73430PD", "G77547TA", "G79666IR", "G80479JV", "G81198YO", "G84225JN", "G85282JO", "G86880BF", "G87123QX", "G90382BL", "G90575OW", "G92135MA", "G92551JA", "G93718GY", "G95977AE", "G98611JV", "G99966GV", "G57321FI", "G02030ZB", "G05724UK", "G08146BT", "G10256JP", "G11870QZ", "G12341GU", "G13910DJ", "G20528HD", "G22625SJ", "G23294PN", "G29299MO", "G29880MM", "G33584ML", "G39188ZX", "G39619TI", "G47012YE", "G47950XN", "G49874UX", "G60177UT", "G63041LO", "G63381RX", "G70375MX", "G72797UR", "G74430RZ", "G80075MS", "G85269DF", "G87051GH", "G95177YH", "G96577RX", "G61491DK", "G06038KF", "G42494UJ", "G96881BQ", "G42518JM", "G81399MY", "G29068FM", "G70323CJ" ], "uniprot_id": "P07996" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Glycosylation affects stability and anti-angiogenic function.", "mechanism": "oHSV-Endostatin reduces tumor vascular density, inhibiting metastasis.", "protein": "Endostatin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "HER2 glycosylation modulates antibody binding and signaling.", "mechanism": "oHSV expressing anti-HER2 antibody blocks HER2 signaling and recruits immune cells for ADCC.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "EGFR glycosylation affects ligand and antibody interactions.", "mechanism": "oHSV expressing anti-EGFR antibody blocks EGFR signaling and reduces immunosuppressive cytokine secretion.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "PD-1 glycosylation regulates surface expression and ligand binding.", "mechanism": "oHSV expressing anti-PD-1 antibody reduces immunosuppression and enhances T cell response.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Soft tissue sarcoma", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "oHSV-GM-CSF boosts anti-tumor immunity in sarcoma models.", "protein": "GM-CSF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Head and neck cancer", "glycan_involvement": "N-glycosylation of gD modulates receptor binding and immune evasion.", "mechanism": "HSV gD mediates viral entry via nectin-1, enabling oHSV infection of tumor cells.", "protein": "HSV glycoprotein D (gD)", "protein_enriched": { "function": "In epithelial cells, the heterodimer gE/gI is required for the cell-to-cell spread of the virus, by sorting nascent virions to cell junctions. Once the virus reaches the cell junctions, virus particle", "gene_name": "gE", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04488" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects OX40L stability and receptor interaction.", "mechanism": "oHSV-OX40L stimulates T cell co-stimulation, enhancing anti-tumor immunity.", "protein": "OX40L", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390425" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry by binding ACE2 and facilitating membrane fusion.", "protein": "SARS-CoV-2 Spike Glycoprotein (Ancestral Variant)", "relationship_type": "causal", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns may differ, affecting antigenicity and antibody binding.", "mechanism": "Variant spike mediates viral entry; mutations in RBD increase ACE2 affinity and immune evasion.", "protein": "SARS-CoV-2 Spike Glycoprotein (Beta Variant, B.1.351)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans influence epitope accessibility for antibody binding.", "mechanism": "Targeted by neutralizing antibodies and vaccines to block ACE2 interaction.", "protein": "SARS-CoV-2 Spike Glycoprotein (Ancestral Variant)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect immune escape and vaccine efficacy.", "mechanism": "Targeted in bivalent vaccines to broaden immune protection against variants.", "protein": "SARS-CoV-2 Spike Glycoprotein (Beta Variant, B.1.351)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation state affects ELISA detection and antigen stability.", "mechanism": "Measured in vaccine formulations by ELISA to assess antigenicity and potency.", "protein": "SARS-CoV-2 Spike Glycoprotein (Ancestral Variant)", "relationship_type": "biomarker", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences epitope presentation and antibody specificity.", "mechanism": "Specifically detected in bivalent vaccines using epitope-blocking ELISA.", "protein": "SARS-CoV-2 Spike Glycoprotein (Beta Variant, B.1.351)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390492" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation may modulate spike binding affinity.", "mechanism": "Host receptor for spike glycoprotein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390492" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect breadth of immune response.", "mechanism": "Inclusion in bivalent vaccines confers cross-protection against multiple variants.", "protein": "SARS-CoV-2 Spike Glycoprotein (Beta Variant, B.1.351)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield modulates immunogenicity.", "mechanism": "Vaccines containing ancestral spike induce neutralizing antibodies.", "protein": "SARS-CoV-2 Spike Glycoprotein (Ancestral Variant)", "relationship_type": "protective", "source_pmcid": "PMC12390492" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may stabilize protein conformation.", "mechanism": "Loss of antigenicity detected by ELISA indicates protein instability or degradation.", "protein": "SARS-CoV-2 Spike Glycoprotein (Beta Variant, B.1.351)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12390492" }, { "confidence": "high", "disease": "Ebola virus infection", "glycan_involvement": "Glycosylation enables multivalent binding to host lectins.", "mechanism": "Mediates viral entry into host cells via interaction with DC-SIGN/R.", "protein": "Ebola virus glycoprotein (EBOV-GP)", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "Ebola virus infection", "glycan_involvement": "Recognizes high-mannose glycans on viral glycoproteins.", "mechanism": "Facilitates Ebola virus entry by binding viral glycoproteins; blocking DC-SIGN inhibits infection.", "protein": "DC-SIGN", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "Ebola virus infection", "glycan_involvement": "Binds multivalent glycans on viral glycoproteins.", "mechanism": "Augments Ebola virus entry; inhibition blocks infection.", "protein": "DC-SIGNR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Recognizes high-mannose N-glycans on gp160.", "mechanism": "Promotes HIV transmission by binding gp160 glycoprotein.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "medium", "disease": "West Nile virus infection", "glycan_involvement": "Binds to viral glycan structures.", "mechanism": "Facilitates West Nile virus transmission by binding viral glycoproteins.", "protein": "DC-SIGNR", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Recognizes viral glycan motifs.", "mechanism": "Mediates HCV entry via glycoprotein binding.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "medium", "disease": "Zika virus infection", "glycan_involvement": "Binds viral glycosylated envelope proteins.", "mechanism": "Facilitates Zika virus entry via glycoprotein interaction.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Recognizes N-glycans on spike protein.", "mechanism": "May facilitate SARS-CoV-2 entry via spike protein glycan recognition.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "Ebola virus infection", "glycan_involvement": "Multivalent glycan display blocks lectin-glycan interactions.", "mechanism": "Blocking DC-SIGN with polyvalent glycan-coated nanoparticles inhibits Ebola virus entry.", "protein": "DC-SIGN", "relationship_type": "protective", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "Ebola virus infection", "glycan_involvement": "Multivalent glycan display blocks lectin-glycan interactions.", "mechanism": "Inhibition of DC-SIGNR with glycan-coated nanoparticles prevents Ebola virus entry.", "protein": "DC-SIGNR", "relationship_type": "protective", "source_pmcid": "PMC12390540" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Minimal glycosylation may affect antigenicity and immune detection.", "mechanism": "Plasma N antigen levels correlate with disease severity and inflammatory markers.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "biomarker", "source_pmcid": "PMC12390639" }, { "confidence": "high", "disease": "Long COVID (PASC)", "glycan_involvement": "Glycosylation may mask epitopes, affecting immune clearance.", "mechanism": "Persistent N protein drives chronic inflammation and immune dysregulation.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "Diabetes (Type 2)", "glycan_involvement": "Minimal glycosylation; mechanism mainly via protein-protein interactions.", "mechanism": "N protein synergizes with TMAO to activate NLRP3 inflammasome, worsening inflammation.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal/exacerbating", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Minimal glycosylation; mechanism mainly via immune modulation.", "mechanism": "N protein amplifies inflammatory responses in obese individuals, increasing severity.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal/exacerbating", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Minimal glycosylation; mechanism mainly via inflammasome activation.", "mechanism": "Hyperphosphatemia amplifies N protein-induced NLRP3 inflammasome activation.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal/exacerbating", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "SUMOylation more relevant than glycosylation for this effect.", "mechanism": "N protein induces Tau phosphorylation via stress granule recruitment, contributing to cognitive impairment.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal/exacerbating", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "Colon and kidney cancers", "glycan_involvement": "Minimal glycosylation; mechanism mainly via protein interactions.", "mechanism": "N protein impedes tumor proliferation and metastasis by destabilizing PKM via YBX1 and G3BP1.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12390639" }, { "confidence": "low", "disease": "Acute angle-closure glaucoma", "glycan_involvement": "Minimal glycosylation; mechanism mainly via immune activation.", "mechanism": "N protein detected in ocular tissues, associated with post-infectious inflammation.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "causal", "source_pmcid": "PMC12390639" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "PTX3 is a glycoprotein; glycosylation may affect binding to N protein.", "mechanism": "PTX3 binds N protein; serum PTX3 correlates with inflammatory markers and disease severity.", "protein": "Long pentraxin 3 (PTX3)", "relationship_type": "biomarker", "source_pmcid": "PMC12390639" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N- and O-glycosylation modulates antigenicity and immune response.", "mechanism": "Heavily glycosylated S protein is main vaccine target; glycosylation affects immune evasion.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390639" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Nrf1 is an N-glycoprotein; its activation requires deglycosylation by NGLY1.", "mechanism": "HCV infection reduces Nrf1 protein levels and impairs Nrf1/ARE-mediated gene expression, favoring viral morphogenesis.", "protein": "Nrf1", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "Steatosis", "glycan_involvement": "Deglycosylation of Nrf1 is required for its activation; impaired processing affects lipid metabolism.", "mechanism": "Impaired Nrf1 activity in HCV-positive cells leads to elevated cholesterol and lipid droplet accumulation, contributing to steatosis.", "protein": "Nrf1", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "N-glycosylation status of Nrf1 affects its nuclear translocation and function.", "mechanism": "Inhibition of Nrf1 correlates with a kinome profile characteristic of enhanced inflammation in HCV-infected cells.", "protein": "Nrf1", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "Nrf1 deglycosylation is necessary for cholesterol sensing and removal.", "mechanism": "Impaired Nrf1 function leads to reduced cholesterol removal and elevated intracellular cholesterol.", "protein": "Nrf1", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Functional Nrf1 requires deglycosylation for nuclear activity.", "mechanism": "Nrf1 protects against oxidative stress and excessive cholesterol, reducing risk of liver cancer; HCV impairs this protection.", "protein": "Nrf1", "relationship_type": "protective", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "E1 is N-glycosylated, affecting virion assembly and infectivity.", "mechanism": "E1 is essential for viral entry and morphogenesis; interacts with host lipoproteins.", "protein": "HCV E1 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "E2 is N-glycosylated, modulating receptor binding and immune recognition.", "mechanism": "E2 mediates host cell entry and immune evasion.", "protein": "HCV E2 glycoprotein", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66299" }, "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Removes N-glycans from Nrf1, essential for its function.", "mechanism": "NGLY1 deglycosylates Nrf1, enabling its activation; targeting NGLY1 could modulate Nrf1 activity in HCV infection.", "protein": "NGLY1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390641" }, { "confidence": "medium", "disease": "Impaired liver regeneration", "glycan_involvement": "N-glycosylation/deglycosylation of Nrf1 regulates its activity.", "mechanism": "Reduced Nrf1 activity in HCV-infected cells impairs redox homeostasis and liver regeneration.", "protein": "Nrf1", "relationship_type": "causal", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Deglycosylation of Nrf1 is required for antioxidant gene induction.", "mechanism": "Nrf1 activation induces antioxidant genes; HCV impairs Nrf1, increasing oxidative stress.", "protein": "Nrf1", "relationship_type": "protective", "source_pmcid": "PMC12390641" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Podoplanin is a mucin-type O-glycosylated glycoprotein; glycosylation is essential for CLEC-2 binding and platelet activation.", "mechanism": "Podoplanin-positive lymphatic endothelial cells show ectasia and proliferation, associated with lymphatic vessel dysfunction and white microthrombi formation.", "protein": "Podoplanin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "Lymphatic dysfunction", "glycan_involvement": "O-glycosylation modulates podoplanin's interaction with CLEC-2 and lymphatic endothelial function.", "mechanism": "Upregulation and proliferation of podoplanin-positive lymphatic vessels contribute to lymphatic obstruction and clot formation.", "protein": "Podoplanin", "relationship_type": "causal", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "Microthrombosis", "glycan_involvement": "O-glycosylation required for podoplanin-CLEC-2 binding and prothrombotic activity.", "mechanism": "Podoplanin-CLEC-2 interaction promotes platelet activation and white microthrombi in lymphatic vessels.", "protein": "Podoplanin", "relationship_type": "causal", "source_pmcid": "PMC12390698" }, { "confidence": "medium", "disease": "Acute lung injury (ALI)", "glycan_involvement": "HMGB1 is not classically glycosylated but interacts with glycan-binding receptors (RAGE); redox forms may affect glycan interactions.", "mechanism": "Translocation and oxidation of HMGB1 in type II pneumocytes marks innate immune activation and lung injury.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390698" }, { "confidence": "medium", "disease": "Respiratory distress", "glycan_involvement": "Surfactant proteins are N- and O-glycosylated, essential for function and stability.", "mechanism": "Hyperplasia of type II pneumocytes and increased surfactant glycoprotein expression maintain alveolar inflation and prevent distress.", "protein": "Surfactant proteins (type II pneumocyte products)", "relationship_type": "protective", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects spike protein binding and viral entry efficiency.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; its glycosylation modulates viral binding and tissue tropism.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12390698" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TMPRSS2 is N-glycosylated, which may affect its protease activity and localization.", "mechanism": "TMPRSS2 primes SARS-CoV-2 spike protein for cell entry; co-localization with ACE2 in lung tissue is critical.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "Microthrombosis", "glycan_involvement": "CLEC-2 recognizes O-glycosylated podoplanin; glycan structure is essential for interaction.", "mechanism": "CLEC-2 on platelets binds podoplanin, triggering platelet activation and clot formation.", "protein": "CLEC-2", "protein_enriched": { "function": "Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro) (PubMed:12804604, PubMed:17585783, PubMed:18198127). The biological function and the GSH-depende", "gene_name": "PTGES2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H7Z7" }, "relationship_type": "causal", "source_pmcid": "PMC12390698" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Platelet glycoproteins are heavily glycosylated, affecting aggregation and clearance.", "mechanism": "Megakaryocyte infiltration and platelet consumption in lung tissue contribute to thrombocytopenia.", "protein": "Platelet glycoproteins (CD61)", "relationship_type": "biomarker", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N- and O-glycosylation on spike protein affects infectivity and antibody recognition.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2; glycosylation shields epitopes and modulates immune evasion.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12390698" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, which modulates receptor binding and immune evasion", "mechanism": "Spike glycoprotein mediates viral entry by binding to host receptors (ACE2, NRP1, CD147, HSPA5)", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12390720" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity and viral entry efficiency", "mechanism": "ACE2 acts as the primary receptor for SARS-CoV-2 spike protein, enabling viral entry", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NRP1 glycosylation may modulate spike interaction", "mechanism": "NRP1 serves as a co-receptor, enhancing SARS-CoV-2 entry", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CD147 glycosylation is essential for spike binding", "mechanism": "CD147 facilitates alternative entry route for SARS-CoV-2", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HSPA5 glycosylation may influence spike interaction", "mechanism": "HSPA5 acts as an auxiliary host entry factor for SARS-CoV-2", "protein": "HSPA5 (GRP78)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike affects TMPRSS2 cleavage efficiency", "mechanism": "TMPRSS2 cleaves spike glycoprotein, facilitating membrane fusion and viral entry", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation modulates susceptibility to cathepsin cleavage", "mechanism": "Cathepsin B cleaves spike protein during endosomal entry route", "protein": "Cathepsin B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Caffeic acid may interfere with glycan-mediated spike-receptor interactions", "mechanism": "Caffeic acid binds spike glycoprotein, inhibiting viral entry", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Caffeic acid may affect glycosylated ACE2-spike binding", "mechanism": "Caffeic acid binds ACE2, potentially blocking spike interaction and viral entry", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of HSPA5 may modulate caffeic acid binding", "mechanism": "Caffeic acid binds HSPA5, possibly interfering with spike-mediated entry", "protein": "HSPA5 (GRP78)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390720" }, { "confidence": "high", "disease": "Plutella xylostella infestation", "glycan_involvement": "GP64 is a glycoprotein mediating membrane fusion and host cell entry.", "mechanism": "Facilitates baculovirus entry and propagation in diamondback moth, enhancing viral control efficacy.", "protein": "GP64", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "high", "disease": "Spodoptera exigua infestation", "glycan_involvement": "F protein is glycosylated, affecting fusion efficiency.", "mechanism": "Mediates viral envelope fusion for baculovirus entry into host cells, critical for infection.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "high", "disease": "Spodoptera frugiperda infestation", "glycan_involvement": "Polyhedrin is glycosylated, stabilizing occlusion bodies.", "mechanism": "Forms occlusion bodies that protect viral particles, increasing environmental persistence and infection rates.", "protein": "Polyhedrin", "protein_enriched": { "function": "Sulfur-rich seed storage protein", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06471" }, "relationship_type": "protective", "source_pmcid": "PMC12390722" }, { "confidence": "medium", "disease": "Plutella xylostella infestation", "glycan_involvement": "Granulin glycosylation aids occlusion body formation.", "mechanism": "Forms granular occlusion bodies in granuloviruses, enhancing viral stability and infectivity.", "protein": "Granulin", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ0" }, "relationship_type": "protective", "source_pmcid": "PMC12390722" }, { "confidence": "medium", "disease": "Plutella xylostella infestation", "glycan_involvement": "Predicted glycosylation increases protein stability.", "mechanism": "Structural protein contributing to viral stability and persistence in host and environment.", "protein": "Ac137/p10", "relationship_type": "protective", "source_pmcid": "PMC12390722" }, { "confidence": "medium", "disease": "Spodoptera exigua infestation", "glycan_involvement": "Glycosylation may affect substrate binding and stability.", "mechanism": "Degrades insect midgut peritrophic membrane, facilitating viral entry and infection.", "protein": "Enhancin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "medium", "disease": "Spodoptera exigua infestation", "glycan_involvement": "Glycosylation may modulate chitin binding.", "mechanism": "Chitin-binding protein in ODV envelope, enhances primary infection in midgut cells.", "protein": "Ac145", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "medium", "disease": "Spodoptera exigua infestation", "glycan_involvement": "Glycosylation may affect chitin interaction.", "mechanism": "Chitin-binding protein, absence reduces virulence and infection establishment.", "protein": "Ac150", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "high", "disease": "Plutella xylostella infestation", "glycan_involvement": "Glycosylation may influence receptor interaction.", "mechanism": "Mediate binding and entry of baculovirus into insect midgut cells, essential for oral infection.", "protein": "Per os infectivity factors (PIFs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390722" }, { "confidence": "high", "disease": "Spodoptera frugiperda resistance to chemical insecticides", "glycan_involvement": "GSTs are glycoproteins; glycosylation may affect stability and activity.", "mechanism": "Upregulated GST enhances detoxification and resistance to chlorantraniliprole.", "protein": "SfGSTe1", "relationship_type": "causal", "source_pmcid": "PMC12390722" }, { "confidence": "high", "disease": "Herpes Simplex Encephalitis (HSE)", "glycan_involvement": "No direct glycosylation reported for \u03b334.5 in this study.", "mechanism": "Upregulation of \u03b334.5 increases neurovirulence and mortality in infected mice, especially in absence of LAT and type-1 IFN.", "protein": "\u03b334.5 (ICP34.5)", "protein_enriched": { "function": "Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of host immune ", "gene_name": "US3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13287" }, "relationship_type": "causal", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "HSV-1 ocular infection", "glycan_involvement": "gB is a heavily glycosylated envelope protein, essential for viral entry and spread.", "mechanism": "gB expression used as a marker for viral replication; levels do not correlate with mortality or neurovirulence.", "protein": "gB (glycoprotein B)", "relationship_type": "biomarker", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "HSV-1 neurovirulence", "glycan_involvement": "LAT is a non-coding RNA; no glycosylation.", "mechanism": "LAT suppresses \u03b334.5 expression, reducing neurovirulence and mortality in infected mice.", "protein": "LAT (Latency-Associated Transcript)", "relationship_type": "protective", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "HSV-1 latency/reactivation", "glycan_involvement": "No glycosylation; acts via RNA-mediated regulation.", "mechanism": "LAT enhances latency and reactivation via anti-apoptotic functions and suppression of lytic genes.", "protein": "LAT (Latency-Associated Transcript)", "relationship_type": "causal", "source_pmcid": "PMC12390724" }, { "confidence": "medium", "disease": "HSV-1-induced apoptosis", "glycan_involvement": "No glycosylation reported.", "mechanism": "ICP0 expression is regulated by LAT; however, in this study, LAT absence did not affect ICP0 levels.", "protein": "ICP0", "relationship_type": "causal", "source_pmcid": "PMC12390724" }, { "confidence": "medium", "disease": "HSV-1-induced apoptosis", "glycan_involvement": "No glycosylation reported.", "mechanism": "ICP4 expression is regulated by LAT; no change in ICP4 levels with LAT deletion in this study.", "protein": "ICP4", "protein_enriched": { "function": "Multifunctional regulator of the expression of viral genes that contributes to the shutoff of host protein synthesis and mediates nuclear export of viral intronless mRNAs. Early in infection, this imm", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10238" }, "relationship_type": "causal", "source_pmcid": "PMC12390724" }, { "confidence": "medium", "disease": "HSV-1 latency/reactivation", "glycan_involvement": "HVEM is a glycoprotein; glycosylation is essential for its function.", "mechanism": "LAT represses HVEM, a host glycoprotein receptor, modulating viral entry and latency.", "protein": "HVEM", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "Herpes Simplex Encephalitis (HSE)", "glycan_involvement": "gB glycosylation is critical for viral infectivity, but not for neurovirulence in this context.", "mechanism": "gB transcript levels do not correlate with neurovirulence or mortality in CNS.", "protein": "gB (glycoprotein B)", "relationship_type": "biomarker", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "HSV-1 neurovirulence", "glycan_involvement": "No glycosylation reported.", "mechanism": "\u03b334.5 inhibits host protein synthesis shutoff and autophagy, promoting neurovirulence.", "protein": "\u03b334.5 (ICP34.5)", "protein_enriched": { "function": "Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of host immune ", "gene_name": "US3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13287" }, "relationship_type": "causal", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "Herpes Simplex Encephalitis (HSE)", "glycan_involvement": "No glycosylation.", "mechanism": "LAT presence reduces risk of HSE by suppressing \u03b334.5 expression and limiting neurovirulence.", "protein": "LAT (Latency-Associated Transcript)", "relationship_type": "protective", "source_pmcid": "PMC12390724" }, { "confidence": "high", "disease": "H1N1-induced liver injury", "glycan_involvement": "SAA is glycosylated; glycosylation may affect stability and aggregation.", "mechanism": "SAA upregulation in liver during H1N1 infection drives inflammation and amyloid formation, contributing to liver injury.", "protein": "Serum Amyloid A (SAA) protein family", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390729" }, { "confidence": "high", "disease": "H1N1-induced liver injury", "glycan_involvement": "LBP is N-glycosylated, affecting secretion and function.", "mechanism": "LBP upregulation enhances innate immune activation and cytokine production, promoting hepatic inflammation.", "protein": "Lipopolysaccharide-binding protein (LBP)", "protein_enriched": { "function": "Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:2412035", "gene_name": "LBP", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G84452RH", "G94470IW" ], "uniprot_id": "P18428" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12390729" }, { "confidence": "medium", "disease": "H1N1-induced liver injury", "glycan_involvement": "Hp is heavily glycosylated; glycosylation modulates immune interactions.", "mechanism": "Hp upregulation reflects acute-phase response and hepatic inflammation.", "protein": "Haptoglobin (Hp)", "relationship_type": "biomarker", "source_pmcid": "PMC12390729" }, { "confidence": "high", "disease": "Neutrophil/macrophage infiltration", "glycan_involvement": "CXCL1 glycosylation may affect chemotactic activity.", "mechanism": "CXCL1 upregulation recruits neutrophils to liver, exacerbating tissue injury.", "protein": "CXCL1", "protein_enriched": { "function": "Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cel", "gene_name": "Cxcl1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12850" }, "relationship_type": "causal", "source_pmcid": "PMC12390729" }, { "confidence": "medium", "disease": "Monocyte activation", "glycan_involvement": "VCAM1 N-glycosylation regulates cell adhesion.", "mechanism": "VCAM1 upregulation promotes monocyte adhesion and infiltration in liver.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC12390729" }, { "confidence": "medium", "disease": "Macrophage infiltration", "glycan_involvement": "CD163 glycosylation modulates receptor function.", "mechanism": "CD163 upregulation marks macrophage activation in inflamed liver.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390729" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "CFH glycosylation affects complement regulation.", "mechanism": "CFH upregulation reflects complement activation during systemic inflammation.", "protein": "Complement Factor H (CFH)", "protein_enriched": { "function": "Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self marke", "gene_name": "CFH", "glycan_count": 140, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00875VP", "G00912UN", "G02815KT", "G04657PL", "G04854VP", "G04909DG", "G05049YU", "G06247RL", "G06356OH", "G07246CJ", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G22140GZ", "G22310AV", "G23863VK", "G26330YA", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G31118FR", "G31852PQ", "G37868ZX", "G40574BA", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45504EY", "G46691LC", "G47737VJ", "G48414YA", "G50045TK", "G51941GC", "G57776ZU", "G59626AS", "G62765YT", "G70441OD", "G70619PT", "G72747WU", "G75983OB", "G79666IR", "G80920RR", "G82830MN", "G83460ZZ", "G84452RH", "G85269DF", "G88374WZ", "G90659AW", "G93860XO", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G00273SJ", "G02886BB", "G07755XJ", "G08290VR", "G10819WX", "G10846ZT", "G12341GU", "G14547CB", "G14972EH", "G20425TQ", "G20528HD", "G31986NC", "G34989PA", "G36131WL", "G37412TK", "G40834TG", "G44215PV", "G46902YN", "G49018RC", "G49642SA", "G49906RN", "G52527GH", "G54010QB", "G57317CE", "G58087IP", "G58954YZ", "G59324HL", "G63980BQ", "G70223PD", "G70232NH", "G70888PK", "G72797UR", "G75221WP", "G77669RF", "G78644BR", "G78787DI", "G80075MS", "G83646BJ", "G84225JN", "G86182NS", "G86880BF", "G90382BL", "G92551JA", "G37881RL", "G43089EG", "G49108TO", "G37399XV", "G57818FI", "G82463GQ", "G47518TP", "G85740DB", "G05933EN", "G07799LX", "G11629QQ", "G15169WU", "G25418HZ", "G31916IQ", "G59536GA", "G60923RB", "G66163OV", "G71146HJ", "G72291OX", "G81263BG", "G85144OK", "G89205CJ", "G94917XT", "G11911BT", "G24084IV", "G43005HM", "G44753VC", "G46524LG", "G57776ZS", "G77547TA", "G80223IX", "G80479JV", "G83633GK", "G87123QX", "G89098OM" ], "uniprot_id": "P08603" }, "relationship_type": "biomarker", "source_pmcid": "PMC12390729" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "IL-6 glycosylation influences receptor binding.", "mechanism": "IL-6 elevation drives systemic inflammatory response and liver injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12390729" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "IL-10 glycosylation modulates anti-inflammatory activity.", "mechanism": "IL-10 upregulation may counteract excessive inflammation.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12390729" }, { "confidence": "high", "disease": "Multi-organ failure", "glycan_involvement": "TNF-alpha glycosylation affects secretion and bioactivity.", "mechanism": "TNF-alpha elevation contributes to systemic inflammation and organ damage.", "protein": "Tumor Necrosis Factor-alpha (TNF-alpha)", "relationship_type": "causal", "source_pmcid": "PMC12390729" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is glycosylated; glycosylation may affect stability and serum half-life.", "mechanism": "Elevated ALT reflects hepatocellular injury and is independently associated with MASLD risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated; glycosylation may modulate enzyme activity.", "mechanism": "Elevated AST indicates liver injury; AST/ALT ratio (De-Ritis) helps distinguish MASLD from other liver diseases.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Ratio reflects glycoprotein levels; glycosylation status may influence serum detection.", "mechanism": "Lower De-Ritis ratio is characteristic of MASLD compared to other liver diseases.", "protein": "AST/ALT ratio (De-Ritis)", "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect ALT clearance and detection.", "mechanism": "Elevated ALT is associated with progression to liver fibrosis in MASLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect AST stability.", "mechanism": "Elevated AST is associated with advanced liver fibrosis and cirrhosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation affects function.", "mechanism": "Lower HDL-C is associated with MASLD; HDL-C may be protective against hepatic steatosis.", "protein": "HDL-C", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "LDL particles contain glycoproteins (e.g., ApoB) with glycosylation affecting receptor binding.", "mechanism": "Elevated LDL-C is associated with MASLD and increased cardiovascular risk.", "protein": "LDL-C", "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "TG particles contain glycoproteins; glycosylation may affect metabolism.", "mechanism": "Elevated TG is independently associated with MASLD risk and reflects hepatic lipid accumulation.", "protein": "Triglyceride-rich lipoproteins (TG)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "T2DM", "glycan_involvement": "Glycosylation may affect ALT serum levels.", "mechanism": "Elevated ALT is associated with increased risk of T2DM in MASLD patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Reflects glycoprotein levels; glycosylation may influence risk marker performance.", "mechanism": "Elevated De-Ritis ratio is associated with increased cardiovascular risk in MASLD.", "protein": "AST/ALT ratio (De-Ritis)", "relationship_type": "biomarker", "source_pmcid": "PMC12391322" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Non-enzymatic glycation of hemoglobin by glucose.", "mechanism": "Reflects average blood glucose over 3 months; higher HbA1c associated with increased mortality risk in AF patients.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "high", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Degree of hemoglobin glycation reflects glycemic variability.", "mechanism": "Measures deviation of actual HbA1c from predicted; low HGI associated with increased ICU and 28-day mortality in AF.", "protein": "Hemoglobin glycation index (HGI)", "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "high", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Acute glycation changes under stress conditions.", "mechanism": "Ratio of acute glucose to HbA1c; high SHR predicts increased 28-day mortality in AF, especially in diabetics.", "protein": "Stress hyperglycemia ratio (SHR)", "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Increased glycation may reflect better adaptation to glycemic stress.", "mechanism": "Higher HGI is protective and associated with reduced short-term mortality in heart failure.", "protein": "Hemoglobin glycation index (HGI)", "relationship_type": "protective", "source_pmcid": "PMC12391337" }, { "confidence": "medium", "disease": "Coronary heart disease (CHD)", "glycan_involvement": "Altered glycation status impacts vascular risk.", "mechanism": "Both high and low HGI levels are associated with adverse cardiovascular events.", "protein": "Hemoglobin glycation index (HGI)", "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Extent of hemoglobin glycation correlates with chronic hyperglycemia.", "mechanism": "Standard marker for long-term glycemic control and diabetes diagnosis.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Acute glycation changes during stress events.", "mechanism": "High SHR associated with poor prognosis in stroke.", "protein": "Stress hyperglycemia ratio (SHR)", "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Reflects acute glycemic stress and glycation.", "mechanism": "Higher SHR is an independent predictor of adverse outcomes in heart failure.", "protein": "Stress hyperglycemia ratio (SHR)", "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "low", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Albumin is a glycoprotein; glycosylation status may affect function.", "mechanism": "Lower albumin levels associated with increased mortality in AF patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391337" }, { "confidence": "medium", "disease": "Atrial fibrillation (AF)", "glycan_involvement": "Glycation degree as a modifiable risk factor.", "mechanism": "Monitoring HGI may guide glycemic management strategies to improve AF outcomes.", "protein": "Hemoglobin glycation index (HGI)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391337" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Not classical glycosylation; extracellular release may be modulated by glycan-binding partners.", "mechanism": "Released as DAMP, activates TLR4 signaling, triggers inflammation.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "causal", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "N-glycosylation required for cell surface expression and ligand binding.", "mechanism": "Activated by HMGB1, initiates MyD88-dependent inflammatory signaling.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Indirect; regulated by upstream glycoproteins (TLR4).", "mechanism": "Transcriptional activation of pro-inflammatory cytokines and MMP-9.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation affects secretion and receptor binding.", "mechanism": "Promotes hepatocyte apoptosis via caspase-3 activation.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Hepatotoxicity", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Activates JAK/STAT3 pathway, amplifies inflammation and fibrosis.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation modulates secretion and receptor interaction.", "mechanism": "Activates hepatic stellate cells, drives fibrogenesis.", "protein": "TGF-\u03b2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12391416" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "N-glycosylation affects secretion and enzymatic activity.", "mechanism": "Degrades extracellular matrix, promotes tissue remodeling and inflammation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391416" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Not glycosylated; regulated by glycoprotein cytokines.", "mechanism": "Activated by IL-6, mediates STAT3 phosphorylation and inflammatory gene expression.", "protein": "JAK2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12391416" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Not glycosylated; regulated by glycoprotein cytokines.", "mechanism": "Transduces signals from JAK2, promotes inflammatory and fibrotic gene expression.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12391416" }, { "confidence": "medium", "disease": "Hepatotoxicity", "glycan_involvement": "Not glycosylated; activation downstream of glycoprotein cytokines.", "mechanism": "Executes apoptosis in hepatocytes downstream of TNF-\u03b1 signaling.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391416" }, { "confidence": "medium", "disease": "Arterial Hypertension", "glycan_involvement": "Glycosylation affects Fibrinogen's structure and drug binding capacity.", "mechanism": "Fibrinogen binds Timolol Maleate, potentially altering drug distribution and efficacy in hypertension treatment.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12391474" }, { "confidence": "medium", "disease": "Myocardial Infarction", "glycan_involvement": "Glycosylation modulates Fibrinogen's plasma stability and drug interactions.", "mechanism": "Fibrinogen interaction with Timolol Maleate may influence drug bioavailability and outcomes post-infarction.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12391474" }, { "confidence": "medium", "disease": "Glaucoma (open-angle, aphakic)", "glycan_involvement": "Glycosylation impacts Fibrinogen's conformation and drug binding.", "mechanism": "Fibrinogen binding may affect Timolol Maleate's pharmacokinetics in glaucoma therapy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12391474" }, { "confidence": "high", "disease": "Coagulation Disorders", "glycan_involvement": "Glycosylation is essential for Fibrinogen's clotting function and drug interaction sites.", "mechanism": "Fibrinogen is central to blood clotting; drug binding may amplify or alter coagulation processes.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391474" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation regulates Fibrinogen's immune interactions.", "mechanism": "Fibrinogen participates in inflammatory responses; drug binding may modulate these effects.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC12391474" }, { "confidence": "medium", "disease": "Wound Healing Impairment", "glycan_involvement": "Glycosylation affects Fibrinogen's role in tissue repair.", "mechanism": "Fibrinogen is involved in wound organization and strength; altered structure from drug binding may impact healing.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. 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"P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391495" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation status may influence antibody recognition.", "mechanism": "HER-2 amplification is a diagnostic/prognostic marker.", "protein": "HER-2", "relationship_type": "biomarker", "source_pmcid": "PMC12391495" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation essential for VEGFR-2 function.", "mechanism": "VEGFR-2 promotes colon tumor angiogenesis; inhibition reduces growth.", "protein": "VEGFR-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391495" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation modulates EGFR activity.", "mechanism": "EGFR signaling implicated in prostate cancer progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and 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"G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391495" }, { "confidence": "high", "disease": "Drug-resistant infections", "glycan_involvement": "N-glycosylation required for proper folding and membrane localization.", "mechanism": "P-gp mediates drug efflux, contributing to multidrug resistance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12391495" }, { "confidence": "low", "disease": "Drug-resistant infections", "glycan_involvement": "Glycosylation affects EGFR-mediated signaling in immune cells.", "mechanism": "EGFR inhibitors may modulate immune response and infection susceptibility.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391495" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "N-glycosylation impacts HER-2 function.", "mechanism": "HER-2 mutations/overexpression found in some lung cancers; inhibition may be beneficial.", "protein": "HER-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391495" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation modulates HDL function and anti-inflammatory properties.", "mechanism": "Major protein in large HDL particles; higher levels inversely associated with preeclampsia risk.", "protein": "Apolipoprotein AI (APOA1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation affects HDL particle stability and function.", "mechanism": "Increased APOA2 in large HDL may inhibit hepatic lipase, maintaining lipid homeostasis and reducing preeclampsia risk.", "protein": "Apolipoprotein AII (APOA2)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation influences enzyme activity and HDL association.", "mechanism": "Reduced PON1 activity in HDL of preeclampsia patients impairs antioxidant defense.", "protein": "Paraoxonase-1 (PON1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391528" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation required for enzymatic activity.", "mechanism": "LCAT in HDL supports cholesterol efflux and vascular health; dysfunction may contribute to preeclampsia.", "protein": "Lecithin-cholesterol acyltransferase (LCAT)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12391528" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation affects VLDL secretion and metabolism.", "mechanism": "Elevated VLDL particles and APOB associated with increased preeclampsia risk.", "protein": "VLDL apolipoproteins (e.g., APOB)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12391528" }, { "confidence": "high", "disease": "Preeclampsia", "glycan_involvement": "Glycoprotein composition and glycosylation regulate HDL size and function.", "mechanism": "Large and extra-large HDL particles inversely associated with preeclampsia and HELLP syndrome.", "protein": "HDL particles (XL-HDL, L-HDL)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "medium", "disease": "Early-onset preeclampsia", "glycan_involvement": "N-glycosylation critical for IGFBP1 stability and function.", "mechanism": "BCAA deprivation reduces IGFBP1, impairing trophoblast migration and placental development.", "protein": "Insulin-like growth factor-binding protein 1 (IGFBP1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "medium", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation modulates LDL receptor binding and clearance.", "mechanism": "Altered LDL metabolism observed in preeclampsia; increased LDL particles may contribute to endothelial dysfunction.", "protein": "LDL apolipoproteins (e.g., APOB)", "relationship_type": "biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "Glycosylation affects IDL metabolism.", "mechanism": "Disturbances in IDL subclasses associated with preeclampsia risk.", "protein": "IDL apolipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "low", "disease": "Preeclampsia", "glycan_involvement": "N-glycosylation modulates APOE receptor interactions.", "mechanism": "APOE in HDL/VLDL may influence lipid transport and inflammation in preeclampsia.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC12391528" }, { "confidence": "high", "disease": "Sandhoff disease", "glycan_involvement": "Hex\u03b2 is required for degradation of glycan moieties on gangliosides and glycoproteins.", "mechanism": "Deficiency of Hex\u03b2 (due to HEXB gene loss) leads to accumulation of GM2 ganglioside and glycoproteins, causing lysosomal dysfunction and neurodegeneration.", "protein": "\u03b2-hexosaminidase (Hex\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391554" }, { "confidence": "high", "disease": "Neurodegeneration", "glycan_involvement": "Failure to degrade glycan-containing substrates in neurons.", "mechanism": "Loss of microglial Hex\u03b2 impairs neuronal lysosomal function, leading to neuronal apoptosis and neurodegeneration.", "protein": "\u03b2-hexosaminidase (Hex\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391554" }, { "confidence": "high", "disease": "Lysosomal storage disorders (LSDs)", "glycan_involvement": "Impaired glycan catabolism in lysosomes.", "mechanism": "Hex\u03b2 deficiency is a prototypical cause of LSDs via substrate accumulation.", "protein": "\u03b2-hexosaminidase (Hex\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391554" }, { "confidence": "high", "disease": "Neuronal apoptosis", "glycan_involvement": "Glycan substrate accumulation triggers apoptosis.", "mechanism": "Neuronal uptake of microglial Hex\u03b2 is necessary to prevent apoptosis; loss leads to apoptotic gene signatures.", "protein": "\u03b2-hexosaminidase (Hex\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391554" }, { "confidence": "medium", "disease": "White matter neurodegeneration", "glycan_involvement": "Accumulation of glycosphingolipids and glycoproteins in white matter.", "mechanism": "Deficiency leads to region-specific vulnerability, especially in white matter (corpus callosum).", "protein": "\u03b2-hexosaminidase (Hex\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12391554" }, { "confidence": "medium", "disease": "Sandhoff disease", "glycan_involvement": "CTSD is a glycoprotein involved in lysosomal protein degradation.", "mechanism": "Upregulated in myeloid cells in Hexb-deficient mice, reflecting lysosomal stress.", "protein": "Cathepsin D (CTSD)", "protein_enriched": { "function": "Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation", "gene_name": "Ctsd", "glycan_count": 12, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05724UK", "G06110VR", "G39188ZX", "G41247ZX", "G49108TO", "G00406II", "G11870QZ", "G25637MV", "G66538GV", "G74724QE", "G84820NF", "G93180LE" ], "uniprot_id": "P18242" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391554" }, { "confidence": "medium", "disease": "Sandhoff disease", "glycan_involvement": "CLU is a secreted glycoprotein; glycosylation affects its function.", "mechanism": "Upregulated in astrocytes in SD, associated with neurotoxicity and lysosomal dysfunction.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC12391554" }, { "confidence": "medium", "disease": "Sandhoff disease", "glycan_involvement": "APOE is glycosylated; glycan status may modulate its neuroimmune roles.", "mechanism": "Upregulated in astrocytes and myeloid cells in SD, linked to neuroinflammation.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC12391554" }, { "confidence": "medium", "disease": "Sandhoff disease", "glycan_involvement": "LAMP1 is a heavily glycosylated lysosomal membrane protein.", "mechanism": "Accumulation in neurons indicates lysosomal dysfunction in SD.", "protein": "LAMP1", "protein_enriched": { "function": "Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). 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Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate rece", "gene_name": "M6PR", "glycan_count": 82, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G11942GC", "G92406TI", "G65953PF", "G01650EU", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G25637MV", "G39188ZX", "G62765YT", "G64527OM", "G72735IY", "G02815KT", "G02886BB", "G04657PL", "G04854VP", "G07246CJ", "G10773YW", "G10846ZT", "G13131HA", "G14547CB", "G15664MX", "G18183SM", "G20312EM", "G20706XG", "G23984SE", "G27058EU", "G27126ED", "G28541PG", "G29184RN", "G29299MO", "G30248BL", "G30970QQ", "G31028YV", "G31544HA", "G31852PQ", "G31986NC", "G33416PL", "G37692EO", "G39446WN", "G40834TG", "G41071NU", "G41840AI", "G43734MM", "G45395BF", "G46450MZ", "G46691LC", "G48414YA", "G49018RC", "G49589RB", "G49642SA", "G50282JC", "G55132BD", "G57776ZS", "G59626AS", "G59924QI", "G60834IK", "G66163OV", "G68490OW", "G68735SN", "G70232NH", "G70441OD", "G72747WU", "G72797UR", "G72951AH", "G75983OB", "G79666IR", "G81124ET", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90575OW", "G90659AW", "G95133RI", "G96091TT", "G96577RX", "G99668VU", "G49108TO" ], "uniprot_id": "P20645" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391554" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "N-glycosylation required for ER localization and chaperone function.", "mechanism": "Upregulated by melatonin-induced ER stress, marks UPR activation and apoptosis.", "protein": "GRP78 (BiP)", "relationship_type": "biomarker", "source_pmcid": "PMC12391747" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "N-glycosylation affects folding and ER membrane localization.", "mechanism": "Melatonin activates PERK, triggering proapoptotic UPR signaling; PERK knockdown increases apoptosis under ER stress.", "protein": "PERK (EIF2AK3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Choriocarcinoma", "glycan_involvement": "N-glycosylation status determines ATF6 activation and nuclear translocation.", "mechanism": "ATF6 cleavage (glycosylation-dependent) marks ER stress; tunicamycin (not melatonin) activates ATF6.", "protein": "ATF6", "relationship_type": "biomarker", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Choriocarcinoma", "glycan_involvement": "N-glycosylation required for ER membrane localization.", "mechanism": "Upregulated by melatonin, but downstream signaling (XBP1 splicing) not activated.", "protein": "IRE1\u03b1", "protein_enriched": { "function": "Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:", "gene_name": "ERN1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G41247ZX", "G57321FI" ], "uniprot_id": "O75460" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391747" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "Indirect; regulated by UPR glycoproteins.", "mechanism": "Melatonin-induced PERK activation increases CHOP, driving apoptosis.", "protein": "CHOP (DDIT3)", "relationship_type": "causal", "source_pmcid": "PMC12391747" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "Indirect; downstream of glycoprotein UPR sensors.", "mechanism": "PERK activation by melatonin increases ATF4, promoting proapoptotic gene expression.", "protein": "ATF4", "protein_enriched": { "function": "Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cel", "gene_name": "ATF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P18848" }, "relationship_type": "causal", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Choriocarcinoma", "glycan_involvement": "Not directly glycosylated; downstream of UPR glycoprotein signaling.", "mechanism": "Melatonin increases cleaved PARP, indicating apoptosis via UPR.", "protein": "Cleaved PARP", "protein_enriched": { "function": "The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle", "gene_name": "PDHA1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08559" }, "relationship_type": "biomarker", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects function.", "mechanism": "PERK associated with poor prognosis and immune infiltration.", "protein": "PERK (EIF2AK3)", "relationship_type": "causal", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "Indirect; downstream of glycoprotein UPR sensors.", "mechanism": "ATF4 overexpression increases multidrug resistance; knockout increases chemotherapy sensitivity.", "protein": "ATF4", "protein_enriched": { "function": "Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cel", "gene_name": "ATF4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P18848" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391747" }, { "confidence": "medium", "disease": "Colon cancer", "glycan_involvement": "N-glycosylation required for function.", "mechanism": "PERK inhibition impedes tumor growth and increases chemotherapy sensitivity.", "protein": "PERK (EIF2AK3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12391747" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Bcl-2 glycosylation may affect stability and apoptotic signaling.", "mechanism": "Sertraline downregulates Bcl-2, restoring apoptotic sensitivity and promoting cell death.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "TCTP glycosylation may modulate its oncogenic activity.", "mechanism": "Sertraline destabilizes TCTP, leading to p53 stabilization and impaired DNA repair.", "protein": "TCTP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Rad51 glycosylation may influence DNA repair efficiency.", "mechanism": "Sertraline inhibits Rad51, impairing homologous recombination and DNA repair.", "protein": "Rad51", "protein_enriched": { "function": "Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:223253", "gene_name": "RAD51", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q06609" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "DR5 glycosylation is critical for ligand binding and apoptotic signaling.", "mechanism": "Sertraline upregulates DR5, sensitizing TRAIL-resistant cells to apoptosis.", "protein": "DR5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "MRP1 glycosylation affects transporter localization and function.", "mechanism": "Sertraline inhibits MRP1, reversing drug resistance and increasing chemotherapy efficacy.", "protein": "MRP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "P-gp glycosylation is essential for membrane trafficking and drug efflux.", "mechanism": "Sertraline inhibits P-gp, increasing intracellular drug accumulation and restoring sensitivity.", "protein": "P-gp", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "MRP7 glycosylation modulates transporter activity.", "mechanism": "Sertraline inhibits MRP7, enhancing chemotherapy response in resistant cells.", "protein": "MRP7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may regulate stability and nuclear localization.", "mechanism": "Sertraline upregulates p21 and p27, inducing cell cycle arrest and apoptosis.", "protein": "CDK inhibitors (p21, p27)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Ki67 glycosylation may affect its detection and function.", "mechanism": "Sertraline reduces Ki67 expression, indicating decreased proliferation.", "protein": "Ki67", "protein_enriched": { "function": "Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:3287", "gene_name": "MKI67", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P46013" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392137" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "SOX2 glycosylation may influence transcriptional activity.", "mechanism": "Sertraline downregulates SOX2, impairing stemness and tumor-initiating capacity.", "protein": "SOX2", "protein_enriched": { "function": "Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarit", "gene_name": "SOX2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL" ], "uniprot_id": "P48431" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392137" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike protein binding and viral entry.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2 spike glycoprotein, facilitating viral infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12392485" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ISG15 is a glycoprotein; glycosylation may affect secretion and immune modulation.", "mechanism": "ISG15 is upregulated during SARS-CoV-2 infection and orchestrates antiviral immune responses.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392485" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Binds beta-galactoside glycans; glycosylation status affects immune cell interactions.", "mechanism": "Galectin-9 is highly expressed in COVID-19 patients and modulates inflammation and viral replication.", "protein": "LGALS9 (Galectin-9)", "relationship_type": "biomarker", "source_pmcid": "PMC12392485" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Acts on N-glycans during glycoprotein quality control.", "mechanism": "EDEM3 mediates ER-associated degradation of misfolded glycoproteins; downregulation may impair viral glycoprotein processing.", "protein": "EDEM3", "protein_enriched": { "function": "", "gene_name": "STK3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NBU1" }, "relationship_type": "causal", "source_pmcid": "PMC12392485" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ADAM10 activity and substrate recognition.", "mechanism": "ADAM10 regulates cytokine production and proteolytic cleavage of cell surface proteins, influencing SARS-CoV-2 entry.", "protein": "ADAM10", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392485" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate vimentin's extracellular interactions.", "mechanism": "Vimentin facilitates pathogen binding to cell surface and persistence, implicated in SARS-CoV-2 infection.", "protein": "VIM (Vimentin)", "relationship_type": "causal", "source_pmcid": "PMC12392485" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein stability and immune signaling.", "mechanism": "TNFAIP3 is upregulated in response to SARS-CoV-2 and modulates inflammation.", "protein": "TNFAIP3", "protein_enriched": { "function": "Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pat", "gene_name": "TNFAIP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21580" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392485" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may affect nuclear localization and transcriptional activity.", "mechanism": "IRF9 forms ISGF3 complex, activating antiviral interferon responses.", "protein": "IRF9", "protein_enriched": { "function": "Transcription factor that plays an essential role in anti-viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kin", "gene_name": "IRF9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q00978" }, "relationship_type": "protective", "source_pmcid": "PMC12392485" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may regulate STAT1 activation and signaling.", "mechanism": "STAT1 mediates interferon signaling and antiviral defense.", "protein": "STAT1", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578,", "gene_name": "STAT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42224" }, "relationship_type": "protective", "source_pmcid": "PMC12392485" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate MAPK3 activity and protein-protein interactions.", "mechanism": "MAPK3 is upregulated in SARS-CoV-2 infection, driving inflammatory and antiviral responses.", "protein": "MAPK3", "relationship_type": "causal", "source_pmcid": "PMC12392485" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Not directly discussed; AST may be glycosylated, but glycosylation not addressed in this study.", "mechanism": "Elevated AST reflects hepatocellular injury in ICP; used in APRI and De Ritis ratio.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Not directly discussed; ALT may be glycosylated, but glycosylation not addressed in this study.", "mechanism": "Elevated ALT reflects hepatocellular injury in ICP; used in De Ritis ratio.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "medium", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Platelet surface glycoproteins are critical for function, but not discussed in this study.", "mechanism": "Platelet count is reduced in severe ICP; used in APRI calculation.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not discussed.", "mechanism": "APRI (AST/platelet ratio) originally developed for liver fibrosis/cirrhosis assessment.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Intrahepatic cholestasis of pregnancy (ICP)", "glycan_involvement": "Bile acid transporters are glycoproteins, but not discussed in this study.", "mechanism": "Elevated serum bile acids are the gold standard for ICP diagnosis and severity.", "protein": "Serum bile acids", "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Adverse perinatal outcomes (preterm birth, NICU admission)", "glycan_involvement": "Not discussed.", "mechanism": "Elevated APRI (AST/platelet ratio) correlates with increased NICU admission, lower gestational age, and birth weight.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Adverse perinatal outcomes (preterm birth, NICU admission)", "glycan_involvement": "Not discussed.", "mechanism": "Lower De Ritis ratio (AST/ALT) is associated with ICP and adverse neonatal outcomes.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Not discussed.", "mechanism": "APRI is used for cirrhosis assessment in other contexts; ICP may progress to cirrhosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Adverse perinatal outcomes (preterm birth, NICU admission)", "glycan_involvement": "Not discussed.", "mechanism": "Higher serum bile acids correlate with increased risk of adverse neonatal outcomes.", "protein": "Serum bile acids", "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not discussed.", "mechanism": "Platelet count reduction is part of APRI, which is used for liver fibrosis assessment.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12392505" }, { "confidence": "high", "disease": "Surfactant Dysfunction Disorders", "glycan_involvement": "ABCA3 is a glycoprotein; glycosylation affects trafficking and function.", "mechanism": "ABCA3 mutations impair phospholipid transport to lamellar bodies, disrupting surfactant homeostasis.", "protein": "ABCA3", "protein_enriched": { "function": "Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar b", "gene_name": "ABCA3", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G92050GC" ], "uniprot_id": "Q99758" }, "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "high", "disease": "Childhood Interstitial Lung Disease (ILD)", "glycan_involvement": "KL-6 is a heavily O-glycosylated mucin; glycosylation is essential for its biomarker function.", "mechanism": "Elevated KL-6 reflects alveolar epithelial damage and disease severity.", "protein": "KL-6 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392539" }, { "confidence": "high", "disease": "Surfactant Dysfunction Disorders", "glycan_involvement": "No direct glycosylation, but interacts with glycoprotein-rich surfactant.", "mechanism": "SFTPC mutations lead to abnormal surfactant protein C processing, causing ILD.", "protein": "SFTPC", "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "medium", "disease": "Diffuse Alveolar Hemorrhage (DAH)", "glycan_involvement": "Glycosylation may affect ABCA3 stability and immune interactions.", "mechanism": "ABCA3 mutations may predispose to DAH via surfactant dysfunction and immune dysregulation.", "protein": "ABCA3", "protein_enriched": { "function": "Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar b", "gene_name": "ABCA3", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G92050GC" ], "uniprot_id": "Q99758" }, "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "medium", "disease": "Diffuse Alveolar Hemorrhage (DAH)", "glycan_involvement": "O-glycosylation critical for KL-6 detection.", "mechanism": "KL-6 is elevated in DAH, reflecting epithelial injury.", "protein": "KL-6 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392539" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "Glycosylation may modulate ABCA3 function in alveolar cells.", "mechanism": "ABCA3 mutations increase risk of pulmonary hypertension secondary to ILD.", "protein": "ABCA3", "protein_enriched": { "function": "Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar b", "gene_name": "ABCA3", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G92050GC" ], "uniprot_id": "Q99758" }, "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "high", "disease": "Childhood Interstitial Lung Disease (ILD)", "glycan_involvement": "Indirect; SFTPC interacts with glycoprotein surfactant matrix.", "mechanism": "SFTPC mutations cause milder ILD phenotypes compared to ABCA3/NKX2-1.", "protein": "SFTPC", "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "high", "disease": "Surfactant Dysfunction Disorders", "glycan_involvement": "Indirect; regulates glycoprotein gene expression.", "mechanism": "NKX2-1 mutations disrupt transcription of surfactant protein and ABCA3 genes, causing severe ILD.", "protein": "NKX2-1", "relationship_type": "causal", "source_pmcid": "PMC12392539" }, { "confidence": "low", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "ABCA3 mutations may be linked to autoimmune manifestations including arthritis.", "protein": "ABCA3", "protein_enriched": { "function": "Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar b", "gene_name": "ABCA3", "glycan_count": 1, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G92050GC" ], "uniprot_id": "Q99758" }, "relationship_type": "association", "source_pmcid": "PMC12392539" }, { "confidence": "medium", "disease": "Pulmonary Hypertension", "glycan_involvement": "O-glycosylation required for KL-6 function.", "mechanism": "KL-6 levels correlate with severity of pulmonary hypertension in ILD.", "protein": "KL-6 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC12392539" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SAKI)", "glycan_involvement": "GDF11 is a secreted glycoprotein; glycosylation may affect stability and receptor binding.", "mechanism": "Attenuates SAKI by reducing inflammation, coagulation, and oxidative stress via PGC-1\u03b1/Nrf2 activation.", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal tubular injury", "glycan_involvement": "Glycosylation may modulate GDF11 secretion and activity.", "mechanism": "Reduces tubular injury markers (KIM-1, NGAL) and histopathological damage in SAKI.", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal apoptosis", "glycan_involvement": "Glycosylation may influence GDF11's anti-apoptotic signaling.", "mechanism": "Decreases renal apoptosis (TUNEL, caspase-3, Bax/Bcl-2 ratio) in SAKI.", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal inflammation", "glycan_involvement": "Glycosylation may affect GDF11's interaction with immune cells.", "mechanism": "Suppresses macrophage infiltration and proinflammatory cytokine expression (TNF-\u03b1, IL-6, IL-1\u03b2, MCP-1).", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal coagulation abnormality", "glycan_involvement": "Glycosylation may impact GDF11's stability and function in coagulation pathways.", "mechanism": "Reduces fibrin deposition, thrombin, TF, PAI-1, and restores platelet count.", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Oxidative stress in kidney", "glycan_involvement": "Glycosylation may regulate GDF11's bioactivity and receptor binding.", "mechanism": "Activates Nrf2-mediated antioxidant response (HO-1, NQO-1, SOD, CAT, GSH-Px), reducing ROS and MDA.", "protein": "GDF11", "relationship_type": "protective", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SAKI)", "glycan_involvement": "Nrf2 is a nuclear glycoprotein; glycosylation may affect nuclear translocation and stability.", "mechanism": "Essential for GDF11-mediated renal protection; Nrf2 KO abolishes GDF11's protective effects.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SAKI)", "glycan_involvement": "PGC-1\u03b1 glycosylation may modulate transcriptional coactivator function.", "mechanism": "Required for GDF11-induced Nrf2 activation and renal protection; knockdown diminishes GDF11 effects.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal tubular injury", "glycan_involvement": "KIM-1 is a glycoprotein; glycosylation is essential for its cell surface localization and function.", "mechanism": "Upregulated in SAKI; reduced by GDF11 supplementation.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Renal tubular injury", "glycan_involvement": "NGAL glycosylation affects secretion and stability.", "mechanism": "Elevated in SAKI; reduced by GDF11 supplementation.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12392574" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "CMPK2 regulates UDP-GlcNAc production, impacting O-GlcNAcylation of mitochondrial proteins and immune signaling.", "mechanism": "Upregulation leads to mitochondrial ROS and mtDNA leakage, activating NLRP3 inflammasome and promoting inflammation.", "protein": "CMPK2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "Rheumatoid arthritis (RA)", "glycan_involvement": "UDP-sugar derivatives from CMPK2 activity affect glycosaminoglycan biosynthesis in joint tissues.", "mechanism": "Regulates synovial inflammation via mtDNA-cGAS-STING pathway; influences chondrocyte homeostasis.", "protein": "CMPK2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "CMPK2-driven UDP-sugar metabolism may affect endothelial glycoprotein expression and adhesion.", "mechanism": "Promotes mtDNA synthesis and STING-mediated inflammation in plaques; VCAM-1 upregulates CMPK2.", "protein": "CMPK2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "Metabolic dysfunction-associated steatohepatitis (MASH)", "glycan_involvement": "CMPK2 activity supports UDP-GlcNAc for O-GlcNAcylation, modulating hepatic metabolic enzymes.", "mechanism": "Upregulation drives NLRP3-mediated pyroptosis, inflammation, and fibrosis in liver.", "protein": "CMPK2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12392576" }, { "confidence": "medium", "disease": "Familial brain calcification (FBC)", "glycan_involvement": "Altered nucleotide pools may affect glycosylation of neuronal proteins.", "mechanism": "CMPK2 variants disrupt mtDNA replication and energy production, causing calcification.", "protein": "CMPK2", "relationship_type": "causal", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "Acute lung injury (ALI)", "glycan_involvement": "CMPK2-driven UDP-sugar metabolism may influence glycosylation of lung immune mediators.", "mechanism": "CMPK2 activates NLRP3 inflammasome, worsening lung injury and inflammation.", "protein": "CMPK2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "UDP-sugar derivatives may modulate glycosylation of inflammatory cytokines.", "mechanism": "CMPK2 upregulation increases mtDNA synthesis and NLRP3 activation, exacerbating ARDS.", "protein": "CMPK2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12392576" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "CMPK2 supports nucleotide and UDP-sugar pools for glycosylation needed in tumor growth.", "mechanism": "lncCMPK2 promotes CRC cell proliferation and metastasis via FUBP3/c-Myc axis.", "protein": "CMPK2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12392576" }, { "confidence": "medium", "disease": "Primary Sj\u00f6gren\u2019s syndrome (pSS)", "glycan_involvement": "CMPK2 activity affects glycosylation of glandular proteins, impacting immune cell recruitment.", "mechanism": "Upregulated CMPK2 correlates with immune infiltration and mitochondrial dysfunction in salivary glands.", "protein": "CMPK2", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12392576" }, { "confidence": "medium", "disease": "Dermatomyositis (DM)", "glycan_involvement": "CMPK2-driven UDP-sugar metabolism may affect glycosylation of muscle/skin proteins.", "mechanism": "CMPK2 identified in muscle and skin tissues, associated with immune infiltration and mitochondrial dysfunction.", "protein": "CMPK2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12392576" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its stability and serum half-life.", "mechanism": "Elevated ALT reflects hepatocellular injury and is used to monitor liver health in MASLD.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "AST is glycosylated; glycan structures may influence enzyme activity and clearance.", "mechanism": "Elevated AST indicates liver cell damage and is used alongside ALT for MASLD diagnosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "GGT glycosylation affects its enzymatic activity and serum levels.", "mechanism": "GGT elevation is associated with oxidative stress and liver dysfunction in MASLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation may modulate ALT's serum stability.", "mechanism": "ALT is used to monitor progression from MASLD to MASH (steatohepatitis).", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycan modifications may affect AST's activity and diagnostic value.", "mechanism": "AST is elevated in MASH and correlates with inflammation and fibrosis.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation influences GGT's serum persistence.", "mechanism": "GGT levels can reflect fibrotic progression in chronic liver disease.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect ALT's clearance during fibrosis resolution.", "mechanism": "ALT reduction is associated with regression of fibrosis after lifestyle intervention.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycosylation impacts ALT's serum stability.", "mechanism": "ALT is a key marker for NAFLD diagnosis and monitoring.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "NAFLD", "glycan_involvement": "Glycan structures may influence AST's diagnostic accuracy.", "mechanism": "AST is used to assess liver injury in NAFLD.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "low", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Altered glycosylation patterns may be linked to malignant transformation.", "mechanism": "Elevated GGT is associated with increased risk of progression to hepatocellular carcinoma.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12392582" }, { "confidence": "high", "disease": "Microvascular invasion (MVI)", "glycan_involvement": "TNFR2 is a glycoprotein; glycosylation may affect receptor shedding and stability.", "mechanism": "Elevated serum sTNFR2 predicts presence of MVI in HCC patients; promotes immunosuppressive microenvironment via Treg expansion.", "protein": "sTNFR2", "relationship_type": "biomarker", "source_pmcid": "PMC12392594" }, { "confidence": "high", "disease": "Tumor recurrence after liver transplantation", "glycan_involvement": "Glycosylation may influence sTNFR2 serum stability and detection.", "mechanism": "High sTNFR2 levels stratify risk for posttransplant tumor recurrence in HCC.", "protein": "sTNFR2", "relationship_type": "biomarker", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation modulates TNFR2 function and ligand binding.", "mechanism": "TNFR2 promotes tumor cell proliferation, migration, and vascular infiltration via NF-\u03baB/MAPK pathways.", "protein": "TNFR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Lung metastasis after HCC surgery", "glycan_involvement": "Glycosylation may affect TNFR2 cell surface expression.", "mechanism": "Elevated TNFR2 expression correlates with increased risk of lung metastasis post-HCC surgery.", "protein": "TNFR2", "relationship_type": "biomarker", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Microvascular invasion (MVI)", "glycan_involvement": "BAFF is glycosylated; glycosylation affects secretion and receptor interaction.", "mechanism": "Higher BAFF levels associated with MVI; may promote vascular invasion via chronic inflammation.", "protein": "BAFF", "relationship_type": "biomarker", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Microvascular invasion (MVI)", "glycan_involvement": "AFP glycosylation affects its serum half-life and immunoreactivity.", "mechanism": "High AFP levels associated with MVI and poor differentiation, but low sensitivity limits utility.", "protein": "AFP", "relationship_type": "biomarker", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Microvascular invasion (MVI)", "glycan_involvement": "Osteocalcin is glycosylated; glycosylation may affect its anti-inflammatory activity.", "mechanism": "Lower osteocalcin in MVI+ patients; may inhibit vascular invasion by reducing inflammation.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "protective", "source_pmcid": "PMC12392594" }, { "confidence": "low", "disease": "Microvascular invasion (MVI)", "glycan_involvement": "Glycosylation may affect sTNFR1 stability and function.", "mechanism": "sTNFR1 may inhibit MVI by neutralizing TNF-\u03b1 and protecting vascular endothelium (not statistically significant in this study).", "protein": "sTNFR1", "relationship_type": "protective (hypothesized)", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may influence sTNFR2's role in vascular pathology.", "mechanism": "High sTNFR2 levels double risk of vascular injury.", "protein": "sTNFR2", "relationship_type": "causal", "source_pmcid": "PMC12392594" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation may affect antibody binding and receptor function.", "mechanism": "Anti-TNFR2 antibodies may enhance immunotherapy efficacy in HCC.", "protein": "TNFR2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392594" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function as an acute-phase reactant.", "mechanism": "CRP levels are significantly elevated in elderly patients with sepsis, reflecting systemic inflammation and infection severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "C3 glycosylation is essential for its activation and immune function.", "mechanism": "Lower C3 levels are associated with increased mortality in sepsis, indicating impaired complement-mediated immunity.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "protective", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "C4 glycosylation modulates complement cascade activity.", "mechanism": "Higher C4 levels are protective against mortality in sepsis, reflecting better humoral immune response.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "protective", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IgG Fc glycosylation regulates effector functions and inflammation.", "mechanism": "Reduced IgG levels in sepsis indicate compromised humoral immunity and correlate with poor outcomes.", "protein": "Immunoglobulin G", "relationship_type": "biomarker", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IgM glycosylation affects its pentameric structure and complement activation.", "mechanism": "Lower IgM levels in sepsis reflect impaired early immune response and increased risk of mortality.", "protein": "Immunoglobulin M", "relationship_type": "biomarker", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Procalcitonin is glycosylated, which may affect its serum stability.", "mechanism": "Elevated procalcitonin is associated with sepsis severity and is used for diagnosis and prognosis.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-6 glycosylation may influence receptor binding and signaling.", "mechanism": "IL-6 is markedly elevated in sepsis, driving hyperinflammation and correlating with disease severity.", "protein": "Interleukin-6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "IL-10 glycosylation can modulate its stability and activity.", "mechanism": "IL-10 is elevated in sepsis, mediating immunosuppression and anti-inflammatory effects.", "protein": "Interleukin-10", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12392643" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "TNF\u03b1 glycosylation may affect secretion and receptor interaction.", "mechanism": "Higher TNF\u03b1 levels are associated with lower mortality in sepsis, suggesting a protective inflammatory response.", "protein": "Tumor necrosis factor alpha", "relationship_type": "protective", "source_pmcid": "PMC12392643" }, { "confidence": "medium", "disease": "Viral infection", "glycan_involvement": "IgA glycosylation is critical for mucosal transport and immune exclusion.", "mechanism": "Lower IgA levels are observed in viral infections among elderly, indicating impaired mucosal immunity.", "protein": "Immunoglobulin A", "relationship_type": "biomarker", "source_pmcid": "PMC12392643" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Mucin-type O-glycosylation is essential for CA125's structure and secretion.", "mechanism": "CA125 is released by mesothelial cells in response to serosal stress and inflammation, reflecting systemic congestion and disease severity.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "O-glycosylation enables CA125's mucin-like properties and detection in serum.", "mechanism": "Elevated CA125 predicts increased mortality and hospitalization risk in AHF, correlating with congestion and inflammatory burden.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Chronic Heart Failure (CHF)", "glycan_involvement": "Glycosylation maintains CA125's stability and function as a circulating biomarker.", "mechanism": "Higher CA125 levels are associated with worse outcomes, higher NYHA class, and pleural effusion in CHF.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Pleural Effusion", "glycan_involvement": "Glycosylation is required for CA125 secretion from serosal surfaces.", "mechanism": "CA125 is upregulated by mesothelial cell activation due to serosal fluid overload.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "medium", "disease": "Pericardial Effusion", "glycan_involvement": "O-glycosylation supports CA125's mucin-like structure for serosal release.", "mechanism": "CA125 increases with pericardial stretch and effusion, reflecting serosal involvement.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Ovarian Cancer", "glycan_involvement": "Aberrant glycosylation patterns in cancer increase CA125 expression.", "mechanism": "CA125 is a classic marker for ovarian cancer, especially serous carcinoma.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation affects CA125's serum half-life and clearance.", "mechanism": "CA125 is elevated due to impaired hepatic clearance and serosal inflammation.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "medium", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation ensures CA125's detectability and stability for longitudinal monitoring.", "mechanism": "Serial CA125 measurement can guide diuretic therapy and monitor response to treatment.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation affects NT-proBNP's stability and serum levels.", "mechanism": "NT-proBNP reflects left ventricular wall stress and is correlated with CA125 for congestion assessment.", "protein": "N-terminal pro\u2013B-type natriuretic peptide (NT-proBNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12392669" }, { "confidence": "low", "disease": "Heart Failure (HF)", "glycan_involvement": "Glycosylation modulates CA125's interaction with matrix components.", "mechanism": "CA125 may contribute to cardiac remodeling via effects on extracellular matrix.", "protein": "Carbohydrate Antigen 125 (CA125)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12392669" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Altered glycosylation affects stability and serum half-life.", "mechanism": "Decreased serum albumin reflects impaired hepatic synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation modulates enzyme activity and secretion.", "mechanism": "Elevated levels indicate cholestasis or biliary obstruction.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "Increased AST signals hepatocellular injury.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "Elevated ALT is specific for liver cell injury.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Liver Disease", "glycan_involvement": "Altered glycosylation of globulins and albumin affects ratio.", "mechanism": "Low ratio indicates chronic liver dysfunction.", "protein": "Albumin/Globulin Ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation changes may exacerbate loss of function.", "mechanism": "Hypoalbuminemia is a hallmark of cirrhosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Cancer-associated glycoforms may be present.", "mechanism": "Elevated levels may indicate tumor invasion of biliary tract.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Glycosylation modulates immunoglobulin function.", "mechanism": "Increased globulin levels reflect immune activation.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "medium", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation status may change with disease progression.", "mechanism": "Lower albumin may indicate advanced NAFLD.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Potential impact on enzyme clearance.", "mechanism": "AST/ALT ratio >1 suggests cirrhosis.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12393716" }, { "confidence": "high", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "Glycosylation of F protein is essential for proper folding, stability, and immune evasion.", "mechanism": "RSV F glycoprotein mediates viral entry and fusion with host cells, initiating infection.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12393788" }, { "confidence": "high", "disease": "Severe RSV disease in older adults", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition, influencing disease severity.", "mechanism": "F glycoprotein enables RSV infection, which is more severe in older adults due to immune senescence and comorbidities.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12393788" }, { "confidence": "high", "disease": "Severe RSV disease in immunocompromised patients", "glycan_involvement": "Glycosylation modulates immune escape, increasing risk in immunocompromised patients.", "mechanism": "F glycoprotein-driven RSV infection leads to higher morbidity in immunocompromised hosts.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12393788" }, { "confidence": "high", "disease": "Severe RSV disease in patients with chronic pulmonary or cardiovascular disease", "glycan_involvement": "Glycosylation impacts viral tropism and immune response.", "mechanism": "RSV F glycoprotein facilitates infection, which exacerbates underlying chronic diseases.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC12393788" }, { "confidence": "high", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "Vaccine design uses stabilized prefusion F glycoprotein with defined glycosylation to enhance immunogenicity.", "mechanism": "RSV F glycoprotein is the antigenic target of licensed RSV vaccines for older adults.", "protein": "RSV F glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12393788" }, { "confidence": "medium", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "Glycosylation may affect assay sensitivity and specificity.", "mechanism": "Detection of F glycoprotein by PCR, antigen, or viral culture is used for definitive diagnosis of RSV infection.", "protein": "RSV F glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12393788" }, { "confidence": "high", "disease": "MTM-HCC", "glycan_involvement": "AFP is N-glycosylated; glycosylation affects its serum stability and detection.", "mechanism": "Elevated serum AFP is an independent predictor of MTM subtype in HCC.", "protein": "Alpha-Fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12394088" }, { "confidence": "medium", "disease": "MTM-HCC", "glycan_involvement": "PD-L1 glycosylation modulates its stability and immune recognition.", "mechanism": "PD-L1 is upregulated in tumor cells, mediating immune evasion; anti-PD-L1 therapy may be effective.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394088" }, { "confidence": "medium", "disease": "MTM-HCC", "glycan_involvement": "CMTM6 is a glycoprotein; glycosylation may affect its interaction with PD-L1.", "mechanism": "CMTM6 stimulates PD-L1 production, promoting immune escape in MTM-HCC.", "protein": "CMTM6", "protein_enriched": { "function": "May play a role in tumor angiogenesis", "gene_name": "PLXDC2", "glycan_count": 30, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G08918WF", "G27058EU", "G41071NU", "G43223CG", "G45395BF", "G57776ZS", "G70232NH", "G79666IR", "G84452RH", "G90659AW", "G00912UN", "G04657PL", "G20210JR", "G23294PN", "G40834TG", "G40926MX", "G43669FQ", "G46691LC", "G51653BI", "G59324HL", "G59626AS", "G63041LO", "G83646BJ", "G87123QX", "G92062TF", "G90382BL", "G53434XO", "G29068FM", "G43417UB", "G57321FI" ], "uniprot_id": "Q6UX71" }, "relationship_type": "causal", "source_pmcid": "PMC12394088" }, { "confidence": "medium", "disease": "MTM-HCC", "glycan_involvement": "VEGFA glycosylation influences receptor binding and angiogenic activity.", "mechanism": "MTM-HCC is susceptible to anti-VEGFA antibodies due to angiogenic pathways.", "protein": "VEGFA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394088" }, { "confidence": "medium", "disease": "MTM-HCC", "glycan_involvement": "Ang-2 glycosylation affects its secretion and function.", "mechanism": "MTM-HCC may respond to anti-Ang-2 therapy targeting angiogenesis.", "protein": "Ang-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394088" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Extracellular glycosylation domain critical for ligand binding and receptor function.", "mechanism": "Overexpression promotes angiogenesis (via VEGF), invasion (via STAT3-MMP9), and correlates with poor prognosis.", "protein": "NPRA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation domain mediates ligand recognition and signaling.", "mechanism": "Promotes angiogenesis (HIF-1\u03b1 stabilization, VEGF upregulation), metastasis, stemness, and chemoresistance (MSC-NPRA-FAO axis).", "protein": "NPRA", "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation domain required for ligand binding and signaling.", "mechanism": "Upregulates inflammatory cytokine MIF, promotes tumor growth; inhibition induces apoptosis.", "protein": "NPRA", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12394403" }, { "confidence": "medium", "disease": "Squamous cell carcinoma (tongue/esophageal)", "glycan_involvement": "Glycosylation domain involved in ligand binding.", "mechanism": "Overexpression correlates with invasiveness, promotes angiogenesis and lymphangiogenesis via VEGF-A/C.", "protein": "NPRA", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12394403" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Five extracellular N-glycosylation sites modulate receptor function.", "mechanism": "Downregulation of NPRB/CNP system in prostate tissue correlates with tumor progression.", "protein": "NPRB", "relationship_type": "biomarker/context-dependent", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Solid tumors (pancreatic, breast, colon, melanoma)", "glycan_involvement": "Glycosylation and acylation modifications improve stability and targeting.", "mechanism": "Engineered CNP (dCNP) activates NPRB, normalizes tumor vasculature, enhances drug delivery, and immune response.", "protein": "NPRB", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC12394403" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation not specified for mechanism.", "mechanism": "Upregulated by lncRNA BCYRN1, promotes proliferation and inhibits apoptosis.", "protein": "NPRC", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Clear cell renal cell carcinoma (ccRCC)", "glycan_involvement": "Glycosylation not specified for mechanism.", "mechanism": "High NPRC expression correlates with favorable prognosis; epigenetic repression (by lncRNA MRCCAT1) promotes metastasis via p38-MAPK.", "protein": "NPRC", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Osteosarcoma", "glycan_involvement": "Glycosylation not specified for mechanism.", "mechanism": "Overexpression inhibits proliferation via PI3K/AKT suppression; knockdown promotes growth.", "protein": "NPRC", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12394403" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Glycosylation not specified for mechanism.", "mechanism": "lncRNA FENDRR upregulates NPRC, inhibits proliferation and promotes apoptosis via p38-MAPK pathway.", "protein": "NPRC", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12394403" }, { "confidence": "high", "disease": "Tenosynovial giant cell tumor (TGCT)", "glycan_involvement": "CSF1R is a glycoprotein; glycosylation affects receptor stability and ligand binding.", "mechanism": "CSF1R signaling drives proliferation of tumor-associated macrophages in TGCT; inhibition reduces tumor growth.", "protein": "CSF1R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394515" }, { "confidence": "high", "disease": "Tenosynovial giant cell tumor (TGCT)", "glycan_involvement": "CSF1 glycosylation influences secretion and receptor interaction.", "mechanism": "Overexpression of CSF1 recruits macrophages, promoting TGCT lesion formation.", "protein": "CSF1", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Hepatic injury (drug-induced liver injury)", "glycan_involvement": "Glycosylation modulates CSF1R function in hepatic macrophages.", "mechanism": "CSF1R inhibition by pexidartinib disrupts hepatic macrophage (Kupffer cell) homeostasis, leading to cholestasis and inflammation.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Ocular edema (periorbital swelling)", "glycan_involvement": "Glycosylation affects CSF1R localization in ocular tissues.", "mechanism": "CSF1R inhibition impairs macrophage function in ocular tissues, disrupting fluid homeostasis and causing edema.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Neurological disorders (memory impairment, taste disorder)", "glycan_involvement": "Glycosylation regulates CSF1R trafficking in neural cells.", "mechanism": "CSF1R inhibition depletes microglia, affecting synaptic plasticity and sensory processing.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Fatigue (systemic adverse event)", "glycan_involvement": "Glycosylation may modulate receptor signaling intensity.", "mechanism": "Systemic CSF1R inhibition alters immune cell homeostasis, contributing to fatigue.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Dermatological reactions (hair color changes, alopecia, skin discoloration)", "glycan_involvement": "Glycosylation influences CSF1R function in skin cells.", "mechanism": "CSF1R inhibition affects macrophage-mediated pigment cell regulation in skin and hair follicles.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Gastrointestinal disorders (nausea, constipation)", "glycan_involvement": "Glycosylation may affect receptor-ligand interactions in gut immune cells.", "mechanism": "CSF1R inhibition alters macrophage populations in gut, affecting motility and sensation.", "protein": "CSF1R", "relationship_type": "causal", "source_pmcid": "PMC12394515" }, { "confidence": "medium", "disease": "Sex-dimorphic adverse event susceptibility", "glycan_involvement": "Potential sex-specific glycosylation patterns of CSF1R.", "mechanism": "Sex hormones modulate CSF1R pathway activity, influencing AE risk profiles.", "protein": "CSF1R", "relationship_type": "biomarker", "source_pmcid": "PMC12394515" }, { "confidence": "low", "disease": "Delayed-onset adverse events (>360 days)", "glycan_involvement": "Long-term glycosylation changes may alter receptor function.", "mechanism": "Chronic CSF1R inhibition leads to cumulative tissue effects.", "protein": "CSF1R", "relationship_type": "biomarker", "source_pmcid": "PMC12394515" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated serum CRP reflects increased systemic inflammation in obesity/metabolic syndrome.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "HDL contains glycoproteins (e.g., ApoA-I) whose glycosylation modulates lipid transport.", "mechanism": "Higher HDL levels are associated with reduced cardiovascular risk; FMT increased HDL.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12394558" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB) with glycosylation affecting receptor binding.", "mechanism": "Elevated LDL is a risk factor for cardiovascular disease.", "protein": "Low-density lipoprotein (LDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Insulin is glycosylated, which affects its stability and receptor interaction.", "mechanism": "Impaired insulin sensitivity is central to type 2 diabetes; FMT showed transient improvement.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "medium", "disease": "Abnormal liver function", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its enzymatic activity.", "mechanism": "Elevated GGT indicates liver dysfunction, common in obesity/metabolic syndrome.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "medium", "disease": "Abnormal liver function", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates its activity and stability.", "mechanism": "Elevated ALP is a marker of liver and metabolic dysfunction.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Bacterial glycoproteins interact with host mucosal glycans, modulating metabolism.", "mechanism": "Higher abundance of B. thetaiotaomicron is associated with reduced metabolic syndrome severity after FMT.", "protein": "Bacteroides thetaiotaomicron surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12394558" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Bacterial glycoproteins may influence host glycan metabolism and immune modulation.", "mechanism": "Baseline abundance predicts greater reduction in metabolic syndrome severity after FMT.", "protein": "Agathobaculum butyriciproducans surface glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC12394558" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation of CRP affects its inflammatory activity.", "mechanism": "CRP levels are elevated in obesity, reflecting chronic low-grade inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394558" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "HDL glycoproteins' glycosylation modulates anti-inflammatory properties.", "mechanism": "Higher HDL is associated with improved metabolic health; FMT increased HDL.", "protein": "High-density lipoprotein (HDL)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12394558" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "No direct glycosylation reported for Nrf2; downstream glycoproteins involved.", "mechanism": "Activation of Nrf2 protects against Cr+As-induced oxidative stress and renal injury by upregulating antioxidant enzymes.", "protein": "Nrf2 (NFE2L2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394698" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "No direct glycosylation reported for KEAP1; regulatory role.", "mechanism": "KEAP1 regulates Nrf2 degradation; oxidative stress disrupts KEAP1-Nrf2 interaction, allowing Nrf2 activation and cytoprotection.", "protein": "KEAP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394698" }, { "confidence": "high", "disease": "Oxidative Stress Injury", "glycan_involvement": "HO-1 is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "HO-1 upregulation via Nrf2 pathway provides antioxidant defense in renal tissue against Cr+As toxicity.", "protein": "HO-1 (HMOX1)", "relationship_type": "protective", "source_pmcid": "PMC12394698" }, { "confidence": "high", "disease": "Oxidative Stress Injury", "glycan_involvement": "NQO1 is a glycoprotein; glycosylation may modulate activity.", "mechanism": "NQO1 detoxifies quinones and protects against oxidative damage in kidney cells exposed to Cr+As.", "protein": "NQO1", "protein_enriched": { "function": "Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons ar", "gene_name": "NQO1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15559" }, "relationship_type": "protective", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Oxidative Stress Injury", "glycan_involvement": "SOD2 is glycosylated; glycosylation may influence mitochondrial localization and activity.", "mechanism": "SOD2 converts superoxide radicals to hydrogen peroxide, reducing ROS-mediated renal damage.", "protein": "SOD2", "relationship_type": "protective", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Heavy Metal Nephrotoxicity", "glycan_involvement": "CYP1A1 is glycosylated; glycosylation affects enzyme stability and function.", "mechanism": "CYP1A1 upregulation indicates xenobiotic metabolism activation in response to Cr+As exposure.", "protein": "CYP1A1", "relationship_type": "biomarker", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Nephritic Apoptosis", "glycan_involvement": "CASP8 is glycosylated; glycosylation may regulate activation and apoptosis signaling.", "mechanism": "CASP8 activation triggers apoptotic cascade in renal cells following Cr+As-induced oxidative stress.", "protein": "CASP8", "relationship_type": "causal", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Nephritic Apoptosis", "glycan_involvement": "CASP3 is glycosylated; glycosylation may affect activation and substrate recognition.", "mechanism": "CASP3 executes apoptosis in kidney cells exposed to Cr+As, leading to DNA degradation.", "protein": "CASP3", "relationship_type": "causal", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "No direct glycosylation reported for SIRT1.", "mechanism": "SIRT1 deacetylates and stabilizes Nrf2, enhancing antioxidant response and protecting renal tissue.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12394698" }, { "confidence": "medium", "disease": "Nephritic Apoptosis", "glycan_involvement": "No direct glycosylation reported for KEAP1.", "mechanism": "KEAP1 upregulation suppresses Nrf2, promoting apoptosis under Cr+As stress.", "protein": "KEAP1", "relationship_type": "causal", "source_pmcid": "PMC12394698" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "RAGE is a glycoprotein receptor; glycosylation modulates HMGB1 binding and signaling.", "mechanism": "Extracellular HMGB1 activates TLR2/4 and RAGE, driving NF-\u03baB-mediated inflammation and immunosuppression.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "high", "disease": "Acute Lung Injury (ALI)", "glycan_involvement": "HSP70 interacts with TLR2/4-CD14 glycoprotein complex; glycosylation affects receptor binding.", "mechanism": "HSP70 inhibits NF-\u03baB activation, reducing pro-inflammatory cytokine transcription and improving lung function.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "medium", "disease": "Acute Lung Injury (ALI)", "glycan_involvement": "HSP90 binds CD91 glycoprotein; glycosylation influences immune activation.", "mechanism": "HSP90 upregulates MHC-II and co-stimulatory molecules in DCs, promoting antigen presentation and inflammation.", "protein": "HSP90", "protein_enriched": { "function": "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoe", "gene_name": "HSP90AA1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G11719TC", "G51640FO", "G80920RR", "G49108TO" ], "uniprot_id": "P07900" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "RAGE glycosylation modulates S100A8/A9 binding and downstream signaling.", "mechanism": "Elevated S100A8/A9 activates TLR4/RAGE, triggering NF-\u03baB and NLRP3 inflammasome, correlating with mortality.", "protein": "S100A8/A9 (Calprotectin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12394712" }, { "confidence": "medium", "disease": "Restrictive Allograft Syndrome (RAS)", "glycan_involvement": "RAGE glycosylation affects S100 protein interaction.", "mechanism": "Increased S100 protein levels in BALF indicate graft dysfunction and inflammation.", "protein": "S100A8/A9 (Calprotectin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12394712" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TLR4 glycosylation required for histone recognition and signaling.", "mechanism": "Extracellular histones activate TLR2/4, inducing NF-\u03baB/p38 MAPK, cytokine storm, DIC, and organ injury.", "protein": "Histones (H2A/H2B/H3/H4)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "TLR4 is a glycoprotein; N-glycosylation essential for ligand binding.", "mechanism": "TLR4 recognizes cholesterol crystals and proteoglycans, activating NLRP3 inflammasome and vascular inflammation.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "CD44 glycosylation modulates proteoglycan binding and immune activation.", "mechanism": "Upregulated proteoglycans bind CD44, activating TLR2/4 and promoting synovial inflammation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "MBL is a glycoprotein; glycosylation critical for complement activation.", "mechanism": "Extracellular ATP interacts with MBL, activating complement and amplifying inflammation.", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "RAGE glycosylation regulates ligand binding and downstream signaling.", "mechanism": "RAGE mediates HMGB1 and S100 protein-induced immunosuppression and tumor progression.", "protein": "RAGE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394712" }, { "confidence": "high", "disease": "Ischemia-reperfusion injury (IRI)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "ALT levels increase in response to hepatocyte injury during IRI.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "high", "disease": "Ischemia-reperfusion injury (IRI)", "glycan_involvement": "AST glycosylation may influence its serum half-life.", "mechanism": "AST levels rise with hepatocellular damage during IRI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury (IRI)", "glycan_involvement": "LDH is glycosylated; glycan status may affect release kinetics.", "mechanism": "LDH is released from damaged cells during IRI.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "medium", "disease": "Early allograft dysfunction", "glycan_involvement": "N-glycosylation of prothrombin affects its secretion and activity.", "mechanism": "Prothrombin time reflects synthetic liver function and is altered in graft dysfunction.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury (IRI)", "glycan_involvement": "Cytokine glycosylation modulates receptor binding and immune activation.", "mechanism": "Cytokine release drives inflammatory response in IRI.", "protein": "Cytokines (general)", "relationship_type": "causal", "source_pmcid": "PMC12394759" }, { "confidence": "high", "disease": "Early allograft dysfunction", "glycan_involvement": "Glycosylation may affect ALT serum levels.", "mechanism": "Elevated ALT indicates graft injury and dysfunction.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "high", "disease": "Early allograft dysfunction", "glycan_involvement": "Glycosylation influences AST stability.", "mechanism": "AST elevation signals hepatocellular damage post-transplant.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "medium", "disease": "Hepatocellular injury", "glycan_involvement": "Glycosylation regulates cytokine function.", "mechanism": "Cytokines mediate cell death and inflammation in liver injury.", "protein": "Cytokines (general)", "relationship_type": "causal", "source_pmcid": "PMC12394759" }, { "confidence": "medium", "disease": "End-stage liver disease", "glycan_involvement": "N-glycosylation is essential for prothrombin secretion.", "mechanism": "Reduced prothrombin reflects impaired liver synthetic capacity.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "high", "disease": "Hepatocellular injury", "glycan_involvement": "Glycosylation may affect ALT release.", "mechanism": "ALT is released from injured hepatocytes.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12394759" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation stabilizes PD-L1 and affects antibody binding.", "mechanism": "PD-L1 enables immune evasion; blockade by Atezolizumab restores anti-tumor immunity.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "high", "disease": "HCC", "glycan_involvement": "N-glycosylation of PD-L1 modulates its cell surface expression and immune recognition.", "mechanism": "PD-L1 expression on tumor cells suppresses T-cell activity; Atezolizumab blocks this interaction.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "high", "disease": "RCC", "glycan_involvement": "Glycosylation affects PD-L1 stability and antibody accessibility.", "mechanism": "PD-L1 blockade by Atezolizumab enhances immune-mediated tumor cell killing.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation regulates PD-L1 function and immune checkpoint activity.", "mechanism": "PD-L1 expression correlates with immune escape; Atezolizumab targets PD-L1.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "medium", "disease": "TNBC", "glycan_involvement": "Glycosylation modulates PD-L1 stability and immune evasion.", "mechanism": "PD-L1 expression on tumor cells inhibits anti-tumor immunity; Atezolizumab blocks PD-L1.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "medium", "disease": "Colorectal Cancer", "glycan_involvement": "Glycosylation influences PD-L1 surface expression.", "mechanism": "PD-L1 mediates immune suppression; Atezolizumab restores immune response.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "high", "disease": "RCC", "glycan_involvement": "MET is glycosylated; glycosylation affects receptor function and ligand binding.", "mechanism": "Cabozantinib inhibits MET signaling, reducing tumor growth and angiogenesis.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "high", "disease": "HCC", "glycan_involvement": "VEGFR glycosylation is essential for receptor folding and function.", "mechanism": "Cabozantinib inhibits VEGFR, blocking angiogenesis and tumor progression.", "protein": "VEGFR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "medium", "disease": "Urothelial Carcinoma", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects immune checkpoint blockade efficacy.", "mechanism": "PD-L1 expression enables immune escape; Atezolizumab blocks PD-L1.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "low", "disease": "Medullary Thyroid Cancer (MTC)", "glycan_involvement": "Glycosylation may regulate PD-L1 function in thyroid cancer.", "mechanism": "PD-L1 expression may contribute to immune evasion; potential target for immunotherapy.", "protein": "PD-L1 (Programmed Death-Ligand 1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12394869" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes and modulate binding to CD4", "mechanism": "gp120 binds CD4 to mediate viral entry into host T cells", "protein": "HIV-1 envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CD4 is N-glycosylated, which can affect gp120 binding affinity", "mechanism": "CD4 is the primary receptor for gp120, enabling HIV entry", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "Immune evasion in HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation forms a glycan shield", "mechanism": "Glycan shield on gp120 masks viral epitopes from immune recognition", "protein": "HIV-1 envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12395666" }, { "confidence": "medium", "disease": "T-cell dysfunction in HIV/AIDS", "glycan_involvement": "Glycosylation modulates interaction strength and immune modulation", "mechanism": "gp120-CD4 interaction disrupts T-cell function", "protein": "HIV-1 envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Not glycosylated; no glycan involvement", "mechanism": "Hsp90-Cdc37 PPI stabilizes oncogenic kinases; disruption inhibits tumor growth", "protein": "Hsp90", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Not glycosylated; no glycan involvement", "mechanism": "Cdc37 partners with Hsp90 to chaperone oncogenic proteins", "protein": "Cdc37", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "Infectious diseases (general)", "glycan_involvement": "Glycosylation is essential for antigenicity and detection", "mechanism": "gp120 presence indicates HIV infection", "protein": "HIV-1 envelope glycoprotein gp120", "relationship_type": "biomarker", "source_pmcid": "PMC12395666" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycosylation may modulate CD4 function in immune response", "mechanism": "CD4+ T cell dysfunction is implicated in neurodegeneration during HIV infection", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395666" }, { "confidence": "high", "disease": "Acute Respiratory Infection (ARI)", "glycan_involvement": "N-glycosylation required for proper folding and immune evasion", "mechanism": "Mediates viral entry and syncytia formation in respiratory epithelium", "protein": "RSV F", "relationship_type": "causal", "source_pmcid": "PMC12395677" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "N-glycosylation modulates antigenicity and fusion activity", "mechanism": "Facilitates fusion and infection of lower respiratory tract cells", "protein": "HMPV F", "relationship_type": "causal", "source_pmcid": "PMC12395677" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation shields antigenic sites, affects host range", "mechanism": "Binds sialic acid on host cells, mediates viral entry", "protein": "Influenza HA", "relationship_type": "causal", "source_pmcid": "PMC12395677" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and drug sensitivity", "mechanism": "Cleaves sialic acid to release virions; target for antivirals", "protein": "Influenza NA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395677" }, { "confidence": "high", "disease": "Systemic Inflammatory Response", "glycan_involvement": "Glycosylation essential for ligand binding and function", "mechanism": "Elevated in response to acute viral infection and inflammation", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation affects stability and serum half-life", "mechanism": "Elevated in hRSV and Influenza A(H1N1) indicating liver involvement", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation modulates enzyme activity", "mechanism": "Elevated in hRSV and Influenza A(H1N1) patients", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation regulates platelet aggregation and clearance", "mechanism": "Reduced platelet count in hRSV and Influenza A(H1N1) reflects disease severity", "protein": "Platelet Glycoprotein IIb/IIIa", "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "medium", "disease": "Leukopenia", "glycan_involvement": "Glycosylation modulates immune cell signaling", "mechanism": "Decreased leukocyte count in Influenza A(H1N1) patients", "protein": "Leukocyte CD45", "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation required for enzyme activity and secretion", "mechanism": "Elevated in all infections, especially HMPV, indicating liver involvement", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC12395677" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Likely involved in membrane localization and microglial signaling; specific glycosylation not detailed.", "mechanism": "MS4A6A expression is upregulated in AD patients and correlates with disease severity; protective SNPs increase MS4A6A expression and reduce AD risk.", "protein": "MS4A6A", "protein_enriched": { "function": "Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood", "gene_name": "MIXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2W2" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12395693" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Membrane glycoprotein function may depend on glycosylation for microglial signaling.", "mechanism": "Ms4a6d deficiency in mice impairs microglial amyloid clearance, increases plaque burden, and exacerbates neuroinflammation.", "protein": "Ms4a6d", "relationship_type": "causal/protective", "source_pmcid": "PMC12395693" }, { "confidence": "high", "disease": "Amyloid pathology", "glycan_involvement": "Glycosylation may affect protein stability and microglial interactions.", "mechanism": "MS4A6A SNPs modulate CSF A\u03b242 levels; higher expression promotes amyloid clearance.", "protein": "MS4A6A", "protein_enriched": { "function": "Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood", "gene_name": "MIXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2W2" }, "relationship_type": "causal/protective", "source_pmcid": "PMC12395693" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may modulate receptor signaling and inflammatory response.", "mechanism": "Ms4a6d suppresses NF-\u03baB signaling in microglia; deficiency leads to increased NLRP3 and IL-1\u03b2, promoting inflammation.", "protein": "Ms4a6d", "relationship_type": "causal/protective", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for cell surface expression and function.", "mechanism": "TREM2 mutations are associated with increased AD risk; expression correlates with MS4A6A.", "protein": "TREM2", "protein_enriched": { "function": "Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ", "gene_name": "TREM2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NZC2" }, "relationship_type": "risk/biomarker", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ligand binding and microglial inhibition.", "mechanism": "CD33 mutations increase AD risk; microglial gene.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk/biomarker", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may regulate protein stability and activation.", "mechanism": "NLRP3 upregulated in Ms4a6d-deficient mice, driving inflammasome activation and IL-1\u03b2 release.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "IL-1\u03b2 levels increased in Ms4a6d-deficient mice, indicating heightened inflammation.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Amyloid pathology", "glycan_involvement": "Heavily glycosylated; glycosylation critical for lysosomal targeting.", "mechanism": "Lamp1 marks lysosomal activity in microglia; used to assess amyloid phagocytosis.", "protein": "Lamp1", "relationship_type": "biomarker", "source_pmcid": "PMC12395693" }, { "confidence": "medium", "disease": "Mild cognitive impairment", "glycan_involvement": "Glycosylation may affect protein function in microglia.", "mechanism": "MS4A6A SNPs associated with risk of MCI, a prodromal stage of AD.", "protein": "MS4A6A", "protein_enriched": { "function": "Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood", "gene_name": "MIXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H2W2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395693" }, { "confidence": "high", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "FAM20A is a secreted glycoprotein; glycosylation may affect secretion and function in mineralization.", "mechanism": "Upregulated in KSD; mediates calcium-phosphate metabolism and biomineralization, linked to IL-6/JAK/STAT3 inflammatory signaling.", "protein": "FAM20A", "protein_enriched": { "function": "", "gene_name": "RPS6KL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6S9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12395729" }, { "confidence": "high", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "DHRS9 is glycosylated; glycosylation may modulate stability and immune signaling.", "mechanism": "Upregulated in KSD; involved in oxylipin metabolism and immune regulation, associated with TNF-\u03b1/NF-\u03baB and IL-6/JAK/STAT3 pathways.", "protein": "DHRS9", "protein_enriched": { "function": "3-alpha-hydroxysteroid dehydrogenase that converts 3-alpha-tetrahydroprogesterone (allopregnanolone) to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone (PubMed:11294878, PubM", "gene_name": "DHRS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BPW9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12395729" }, { "confidence": "medium", "disease": "Obesity (OB)", "glycan_involvement": "Glycosylation may regulate FAM20A secretion from adipose tissue.", "mechanism": "Differentially expressed in obesity; links visceral adiposity to renal inflammation via cytokine signaling.", "protein": "FAM20A", "protein_enriched": { "function": "", "gene_name": "RPS6KL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6S9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "medium", "disease": "Obesity (OB)", "glycan_involvement": "Glycosylation may influence DHRS9's immune regulatory functions.", "mechanism": "Differentially expressed in obesity; participates in adipose-driven inflammatory responses.", "protein": "DHRS9", "protein_enriched": { "function": "3-alpha-hydroxysteroid dehydrogenase that converts 3-alpha-tetrahydroprogesterone (allopregnanolone) to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone (PubMed:11294878, PubM", "gene_name": "DHRS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BPW9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation may affect FAM20A's interaction with cytokines.", "mechanism": "Activated by IL-6/JAK/STAT3 pathway; promotes local renal inflammation.", "protein": "FAM20A", "protein_enriched": { "function": "", "gene_name": "RPS6KL1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6S9" }, "relationship_type": "causal", "source_pmcid": "PMC12395729" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Glycosylation may modulate DHRS9's stability and signaling.", "mechanism": "Activated by TNF-\u03b1/NF-\u03baB and JAK/STAT3; modulates inflammatory signaling.", "protein": "DHRS9", "protein_enriched": { "function": "3-alpha-hydroxysteroid dehydrogenase that converts 3-alpha-tetrahydroprogesterone (allopregnanolone) to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone (PubMed:11294878, PubM", "gene_name": "DHRS9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BPW9" }, "relationship_type": "causal", "source_pmcid": "PMC12395729" }, { "confidence": "low", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "N-glycosylation affects SERPINA1's stability and secretion.", "mechanism": "Differentially expressed in KSD; may modulate protease activity in renal tissue.", "protein": "SERPINA1", "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "low", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "O-glycosylation modulates SPP1's interaction with minerals and immune cells.", "mechanism": "Upregulated in KSD; involved in crystal formation and inflammation.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "low", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "Glycosylation affects CHI3L1's stability and immune function.", "mechanism": "Upregulated in KSD; participates in tissue remodeling and inflammation.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "low", "disease": "Kidney stone disease (KSD)", "glycan_involvement": "Glycosylation may regulate SLC7A7's membrane localization.", "mechanism": "Differentially expressed in KSD; may influence amino acid transport and metabolic risk.", "protein": "SLC7A7", "relationship_type": "biomarker", "source_pmcid": "PMC12395729" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "GP60 is a glycoprotein; glycosylation is essential for antigenicity and immune recognition", "mechanism": "GP60 in EVs stimulates host immune response via TLR4/IKK pathway", "protein": "GP60", "protein_enriched": { "function": "May play a role in reproduction", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9U6V9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395738" }, { "confidence": "medium", "disease": "Cryptosporidiosis", "glycan_involvement": "Glycosylation likely contributes to membrane localization and immune stimulation", "mechanism": "CpRom1 in EVs activates splenocytes and immune signaling", "protein": "CpRom1", "relationship_type": "biomarker", "source_pmcid": "PMC12395738" }, { "confidence": "high", "disease": "Giardiasis", "glycan_involvement": "VSPs are heavily glycosylated, mediating immune evasion and host interaction", "mechanism": "VSPs in Giardia EVs disrupt tight junctions and promote Th1 immune response", "protein": "Variable Surface Proteins (VSPs)", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "high", "disease": "Amebiasis", "glycan_involvement": "Glycan moieties are critical for PRR recognition and immune activation", "mechanism": "LPPG on E. histolytica surface triggers TLR2/4/6-mediated inflammation", "protein": "Lipopeptidophosphoglycan (LPPG)", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycosylation may affect enzyme stability and host cell targeting", "mechanism": "Cathepsin B in Giardia EVs contributes to epithelial barrier disruption", "protein": "Cathepsin B", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycosylation facilitates host cell interaction", "mechanism": "Giardins in EVs mediate parasite adhesion and pathogenesis", "protein": "Giardins", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "high", "disease": "Cryptosporidiosis", "glycan_involvement": "Glycosylation forms the protective shell structure", "mechanism": "COWPs confer oocyst resistance to environmental stress and immune attack", "protein": "Cryptosporidium oocyst wall proteins (COWPs)", "relationship_type": "protective", "source_pmcid": "PMC12395738" }, { "confidence": "medium", "disease": "Giardiasis", "glycan_involvement": "Glycolipids interact with immune receptors, influencing inflammation", "mechanism": "EV lipidome modulates immune cell activation and pathogenesis", "protein": "Exosomal lipids (ceramides, cardiolipins)", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "high", "disease": "Blastocystis-associated gut inflammation", "glycan_involvement": "Glycoproteins in EVs modulate cytokine signaling", "mechanism": "EVs increase IL-6, TNF-\u03b1 and decrease IL-10, IL-4, promoting inflammation", "protein": "Blastocystis EV proteins", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "low", "disease": "Giardiasis", "glycan_involvement": "Glycosylation may affect enzyme activity and immune recognition", "mechanism": "Present in Giardia EVs, may contribute to metabolic disruption in host", "protein": "Ornithine carbamoyltransferase", "relationship_type": "causal", "source_pmcid": "PMC12395738" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Claudin-1 is glycosylated, which affects its localization and barrier function.", "mechanism": "SCP increases Claudin-1 expression, enhancing tight junction integrity and mucosal barrier function in aging mice.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "protective", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Glycosylation modulates Zo-1 interactions with other junctional proteins.", "mechanism": "SCP upregulates Zo-1, supporting tight junction assembly and barrier restoration.", "protein": "Zo-1 (TJP1)", "protein_enriched": { "function": "Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin", "gene_name": "Add1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9QYC0" }, "relationship_type": "protective", "source_pmcid": "PMC12395763" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "APP glycosylation affects its processing and aggregation.", "mechanism": "APP expression is upregulated in aging; SCP reduces APP levels, potentially lowering amyloidogenic risk.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395763" }, { "confidence": "medium", "disease": "Age-related cognitive decline", "glycan_involvement": "Glycosylation may regulate P53 stability and activity.", "mechanism": "P53 is upregulated in aging brain; SCP reduces P53, possibly mitigating neuronal senescence.", "protein": "P53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:19556538, PubMed:20673990, PubMed:22726440). Acts as a tumo", "gene_name": "Tp53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02340" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395763" }, { "confidence": "medium", "disease": "Age-related cognitive decline", "glycan_involvement": "Potential glycosylation modulates SIRT1 activity.", "mechanism": "SCP increases SIRT1 expression, promoting anti-aging and neuroprotective effects.", "protein": "SIRT1", "relationship_type": "protective", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Steroid hormone deficiency", "glycan_involvement": "COMT glycosylation affects enzyme stability and activity.", "mechanism": "SCP upregulates COMT, enhancing steroid hormone biosynthesis and cognitive function.", "protein": "COMT", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Steroid hormone deficiency", "glycan_involvement": "UGT1A9 glycosylation is essential for proper enzyme function.", "mechanism": "SCP increases UGT1A9, supporting steroid metabolism and neuroprotection.", "protein": "UGT1A9", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Steroid hormone deficiency", "glycan_involvement": "Glycosylation modulates HSD11B1 activity.", "mechanism": "SCP upregulates HSD11B1, promoting steroid hormone biosynthesis and brain health.", "protein": "HSD11B1", "protein_enriched": { "function": "Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of ", "gene_name": "Clk2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35491" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "O-glycosylation is critical for mucin function and barrier properties.", "mechanism": "SCP increases goblet cell number and mucin secretion, improving mucosal barrier.", "protein": "Mucin (acidic mucins)", "relationship_type": "protective", "source_pmcid": "PMC12395763" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Bacterial glycoproteins interact with host mucins and immune system.", "mechanism": "SCP increases abundance of neuroprotective Eubacterium_brachy_group, linked to reduced neurodegeneration.", "protein": "Eubacterium_brachy_group (bacterial glycoproteins)", "relationship_type": "protective", "source_pmcid": "PMC12395763" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus infection (FIV)", "glycan_involvement": "N-glycosylation sites on gp40 are conserved and may affect antigenicity.", "mechanism": "Antibodies against gp40 are detected by Anigen\u00ae kit for FIV diagnosis.", "protein": "gp40 (FIV envelope transmembrane protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12395775" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus infection (FIV)", "glycan_involvement": "N-glycosylation sites modulate immune recognition and viral infectivity.", "mechanism": "gp120 mediates viral entry and is highly variable, contributing to immune evasion.", "protein": "gp120 (FIV envelope surface protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "medium", "disease": "Immunosuppression", "glycan_involvement": "Glycosylation may affect fusion efficiency and immune escape.", "mechanism": "gp40 is essential for viral fusion and infection of CD4+ T cells, leading to immunodeficiency.", "protein": "gp40 (FIV envelope transmembrane protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus infection (FIV)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Antibodies against p15 detected by SNAP\u00ae kit for FIV diagnosis.", "protein": "p15 (FIV gag matrix protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12395775" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus infection (FIV)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "Antibodies against p24 detected by SNAP\u00ae kit for FIV diagnosis.", "protein": "p24 (FIV gag capsid protein)", "relationship_type": "biomarker", "source_pmcid": "PMC12395775" }, { "confidence": "medium", "disease": "Lymphopenia", "glycan_involvement": "Glycosylation shields epitopes, facilitating persistent infection.", "mechanism": "gp120-mediated infection of CD4+ T cells leads to their depletion.", "protein": "gp120 (FIV envelope surface protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "medium", "disease": "Hyperglobulinemia", "glycan_involvement": "Glycosylation may modulate antigenicity and immune activation.", "mechanism": "Chronic antigenic stimulation by viral glycoproteins induces polyclonal B cell activation.", "protein": "gp120 (FIV envelope surface protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "medium", "disease": "Chronic upper respiratory infection", "glycan_involvement": "Glycosylation may affect immune evasion.", "mechanism": "FIV infection via gp40-mediated entry leads to immunosuppression, predisposing to secondary infections.", "protein": "gp40 (FIV envelope transmembrane protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "low", "disease": "Feline chronic gingivostomatitis", "glycan_involvement": "Glycosylation may affect tissue tropism and immune modulation.", "mechanism": "FIV-induced immunosuppression via gp120 increases risk of chronic oral inflammation.", "protein": "gp120 (FIV envelope surface protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "low", "disease": "Feline infectious anemia", "glycan_involvement": "Indirect; glycosylation may affect viral persistence.", "mechanism": "FIV infection predisposes to anemia via immunosuppression and chronic disease.", "protein": "gp40 (FIV envelope transmembrane protein)", "relationship_type": "causal", "source_pmcid": "PMC12395775" }, { "confidence": "high", "disease": "Retinopathy of Prematurity (ROP)", "glycan_involvement": "VEGF is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Hyperglycemia upregulates VEGF via HIF-1\u03b1 and oxidative stress, driving pathological retinal neovascularization.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "high", "disease": "Retinopathy of Prematurity (ROP)", "glycan_involvement": "IGF-1 glycosylation modulates stability and bioactivity.", "mechanism": "Hyperglycemia suppresses IGF-1, impairing normal retinal vascular development and promoting ROP.", "protein": "IGF-1", "relationship_type": "protective", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "GLUT2 is N-glycosylated; glycosylation affects membrane localization and function.", "mechanism": "Low GLUT2 expression in preterm infants impairs hepatic glucose sensing, leading to persistent endogenous glucose production.", "protein": "GLUT2", "protein_enriched": { "function": "Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "GLUT4 glycosylation is required for proper trafficking and function.", "mechanism": "Low GLUT4 expression reduces glucose uptake in muscle/adipose tissue, contributing to hyperglycemia.", "protein": "GLUT4", "protein_enriched": { "function": "Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:2211693, PubMed:2645527, PubMed:2649253). Response to insulin is regulated by ", "gene_name": "Slc2a4", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19357" }, "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and receptor interaction.", "mechanism": "TNF-\u03b1 induces insulin resistance via modulation of insulin receptor signaling, promoting hyperglycemia.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Retinopathy of Prematurity (ROP)", "glycan_involvement": "IL-6 glycosylation modulates stability and activity.", "mechanism": "Hyperglycemia increases IL-6, promoting retinal vascular inflammation and neovascularization.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "high", "disease": "Retinopathy of Prematurity (ROP)", "glycan_involvement": "AGEs are non-enzymatic glycation products; they disrupt normal glycoprotein function.", "mechanism": "Hyperglycemia leads to AGE accumulation, causing retinal endothelial damage and increased vascular permeability.", "protein": "AGEs", "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Retinopathy of Prematurity (ROP)", "glycan_involvement": "PKC glycosylation may affect localization and activity.", "mechanism": "Hyperglycemia activates PKC, increasing retinal vascular permeability and pathological angiogenesis.", "protein": "PKC", "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Intraventricular Hemorrhage (IVH)", "glycan_involvement": "VEGF glycosylation affects angiogenic potency.", "mechanism": "Hyperglycemia-induced VEGF upregulation increases vascular fragility in the germinal matrix, predisposing to IVH.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "Insulin glycosylation is minimal but may affect receptor binding.", "mechanism": "Insulin therapy reduces hyperglycemia and lowers IVH risk in preterm infants.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "protective", "source_pmcid": "PMC12395794" }, { "confidence": "medium", "disease": "Hypophosphatemia", "glycan_involvement": "Glycosylation affects serum protein stability and phosphorus binding.", "mechanism": "Low serum phosphorus, often bound to glycoproteins, is a marker of malnutrition severity in ED admissions.", "protein": "Phosphorus-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "medium", "disease": "Eating Disorders (ED)", "glycan_involvement": "N-glycosylation modulates ALT secretion and stability.", "mechanism": "Elevated ALT, a glycoprotein, indicates liver stress/damage in severe malnutrition.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "medium", "disease": "Hypokalemia", "glycan_involvement": "Glycosylation influences serum protein function and potassium homeostasis.", "mechanism": "Low serum potassium, partly regulated by glycoproteins, reflects severity of malnutrition in ED.", "protein": "Potassium-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "medium", "disease": "Eating Disorders (ED)", "glycan_involvement": "Glycosylation affects phosphorus transport and protein half-life.", "mechanism": "Hypophosphatemia is more prevalent in severe ED cases, indicating risk for refeeding syndrome.", "protein": "Phosphorus-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "low", "disease": "COVID-19 related mental health disorders", "glycan_involvement": "N-glycosylation modulates ALT activity under stress.", "mechanism": "ALT elevation may reflect stress-induced hepatic changes in patients with COVID-19 related ED admissions.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "low", "disease": "COVID-19 related mental health disorders", "glycan_involvement": "Glycosylation may affect protein-mediated phosphorus levels.", "mechanism": "Lower odds of hypophosphatemia post-COVID-19 outbreak suggest changes in severity of ED admissions.", "protein": "Phosphorus-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "low", "disease": "Eating Disorders (ED)", "glycan_involvement": "Glycosylation impacts potassium channel and transporter function.", "mechanism": "Hypokalemia is a marker of ED severity, especially in restrictive subtypes.", "protein": "Potassium-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12395816" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated NGAL indicates early kidney injury in sepsis; NE reduces NGAL levels.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC12395834" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "KIM-1 is a glycoprotein; glycosylation modulates function and detection.", "mechanism": "KIM-1 is upregulated in kidney injury; NE reduces KIM-1 levels.", "protein": "KIM-1", "protein_enriched": { "function": "Nonheme diiron monooxygenase involved in the biosynthesis of xanthophylls. Specific for beta-ring hydroxylations of beta-carotene. Also has a low activity toward the beta- and epsilon-rings of alpha-c", "gene_name": "BETA-OHASE 1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9SZZ8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395834" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "TNF-\u03b1 is glycosylated, affecting receptor binding and activity.", "mechanism": "TNF-\u03b1 drives inflammatory damage in SA-AKI; NE suppresses TNF-\u03b1 secretion.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395834" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "IL-6 glycosylation regulates secretion and stability.", "mechanism": "IL-6 promotes inflammation and kidney injury; NE reduces IL-6 levels.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12395834" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "IL-1\u03b2 is glycosylated, influencing activity.", "mechanism": "IL-1\u03b2 contributes to inflammatory cascade in SA-AKI; NE shows limited suppression.", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "causal", "source_pmcid": "PMC12395834" }, { "confidence": "medium", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "IL-10 glycosylation affects anti-inflammatory function.", "mechanism": "IL-10 is anti-inflammatory; NE enhances IL-10 secretion in macrophages.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "protective", "source_pmcid": "PMC12395834" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "ZO-1 is glycosylated; glycosylation maintains tight junction integrity.", "mechanism": "ZO-1 loss indicates tubular epithelial damage; NE restores ZO-1 expression.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395834" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "Occludin glycosylation is critical for tight junction function.", "mechanism": "Occludin loss reflects epithelial barrier disruption; NE increases occludin expression.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395834" }, { "confidence": "high", "disease": "Sepsis-associated acute kidney injury (SA-AKI)", "glycan_involvement": "NF-\u03baB p65 is glycosylated; glycosylation may affect nuclear translocation.", "mechanism": "NF-\u03baB activation drives cytokine production; NE inhibits NF-\u03baB activation in macrophages.", "protein": "NF-\u03baB p65", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "RELA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q04206" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395834" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "F4/80 is a glycoprotein; glycosylation affects cell surface expression.", "mechanism": "F4/80 marks macrophage infiltration in kidney; NE reduces F4/80+ cell infiltration.", "protein": "F4/80", "protein_enriched": { "function": "May have regulatory role in cell division or differentiation in response to extracellular signals", "gene_name": "Skil", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q60665" }, "relationship_type": "biomarker", "source_pmcid": "PMC12395834" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "EGFR is a heavily N-glycosylated receptor; glycosylation is essential for its stability and function.", "mechanism": "EGFR is overexpressed in HCC and drives RAS-RAF-MEK-ERK pathway activation; inhibition suppresses tumor growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "GRB2 is a glycoprotein; glycosylation may affect its stability and interactions.", "mechanism": "GRB2 is overexpressed in HCC and mediates EGFR downstream signaling; inhibition disrupts oncogenic signaling.", "protein": "GRB2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "ERK1/2 are glycoproteins; glycosylation may modulate activity.", "mechanism": "ERK1/2 are activated downstream of EGFR; inhibition reduces proliferation and survival of HCC cells.", "protein": "ERK1/2 (MAPK1/MAPK3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "RAF1 is a glycoprotein; glycosylation may influence localization and function.", "mechanism": "RAF1 is part of the RAS-RAF-MEK-ERK pathway; inhibition blocks oncogenic signaling.", "protein": "RAF1", "protein_enriched": { "function": "Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining", "gene_name": "RAF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G47702MW" ], "uniprot_id": "P04049" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "MEK1/2 are glycoproteins; glycosylation may affect kinase activity.", "mechanism": "MEK1/2 are kinases in the EGFR pathway; inhibition suppresses tumor cell proliferation.", "protein": "MEK1/2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "SRC is a glycoprotein; glycosylation may regulate its activity.", "mechanism": "SRC is a hub in oncogenic signaling; inhibition may reduce HCC progression.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a secreted glycoprotein; glycosylation is critical for its secretion and detection.", "mechanism": "AFP is elevated in HCC and used as a diagnostic/prognostic biomarker.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12395921" }, { "confidence": "high", "disease": "Liver cancer", "glycan_involvement": "N-glycosylation of EGFR is required for ligand binding and receptor activation.", "mechanism": "EGFR overexpression/activation promotes liver cancer progression via downstream signaling.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation modulates EGFR function in various cancers.", "mechanism": "EGFR is implicated in ovarian cancer growth; inhibition has antitumor effects.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects EGFR stability and signaling.", "mechanism": "EGFR signaling contributes to breast cancer progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395921" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Integrin \u03b21 is a glycoprotein; glycosylation affects its cell surface expression and function.", "mechanism": "Integrin \u03b21 regulates adipocyte differentiation and insulin signaling; its dysregulation leads to abnormal adipocytes and obesity.", "protein": "Integrin \u03b21", "protein_enriched": { "function": "Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. 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Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-", "gene_name": "ITGB1", "glycan_count": 217, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G49108TO", "G57321FI", "G00406II", "G00912UN", "G01650EU", "G02528FI", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G11870QZ", "G12313PD", "G14260UH", "G14972EH", "G16125XL", "G17208MA", "G23863VK", "G25079LO", "G25451PN", "G27058EU", "G27126ED", "G27915IV", "G28541PG", "G28622IK", "G29545VG", "G30769VJ", "G30970QQ", "G31852PQ", "G35541EV", "G37399XV", "G39188ZX", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G43223CG", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45395BF", "G46503DX", "G46691LC", "G47644PP", "G48584BU", "G49906RN", "G51653BI", "G53075ES", "G55132BD", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63040RU", "G63041LO", "G64527OM", "G65184UU", "G65414LI", "G68490OW", "G70101JE", "G70232NH", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G72797UR", "G76295SF", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G80920RR", "G81637OR", "G82443XX", "G82463GQ", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G85269DF", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90093AU", "G90659AW", "G91636VS", "G92062TF", "G92135MA", "G93718GY", "G95177YH", "G95865ZB", "G99679NM", "G11942GC", "G00273SJ", "G05049YU", "G08290VR", "G11314AS", "G15664MX", "G18647XP", "G22573RC", "G23719VF", "G24528MX", "G27947YN", "G29299MO", "G36379GD", "G37692EO", "G39446WN", "G59924QI", "G69521XL", "G77547TA", "G89045VA", "G90382BL", "G92050GC", "G96091TT", "G98611JV", "G81315DD", "G35029YA", "G37818NZ", "G49955PK", "G57317CE", "G85554PZ", "G11115RO", "G31028YV", "G66163OV", "G75568BH", "G79286RS", "G13131HA", "G25637MV", "G31596OQ", "G50713DU", "G10846ZT", "G11629QQ", "G12341GU", "G15169WU", "G20312EM", "G23165GD", "G31544HA", "G40834TG", "G47012YE", "G47518TP", "G50427EO", "G50856PC", "G56518TU", "G71051TA", "G75983OB", "G76417NN", "G83229XP", "G85677PP", "G94831VI", "G95133RI", "G96577RX", "G25987BV", "G49874UX", "G06356OH", "G11041DA", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G22310AV", "G25520XG", "G29880MM", "G36191CD", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48414YA", "G48954CA", "G50045TK", "G50489VC", "G52527GH", "G53752TA", "G55220VL", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G91365ZQ", "G91413ZX", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P05556" }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation required for integrin \u03b15\u03b21 function.", "mechanism": "Integrin \u03b15\u03b21 activation increases insulin receptor phosphorylation; its dysregulation impairs insulin signaling.", "protein": "Integrin \u03b15\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Integrin \u03b1V\u03b23 is a glycoprotein; glycosylation affects ligand binding.", "mechanism": "Mechanical stress activates integrin \u03b1V\u03b23 in chondrocytes, inducing inflammatory mediators and matrix-degrading enzymes, promoting cartilage degeneration.", "protein": "Integrin \u03b1V\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "high", "disease": "Chronic inflammation", "glycan_involvement": "ANGPTL2 is a secreted glycoprotein; glycosylation required for secretion and function.", "mechanism": "ANGPTL2 binds integrin \u03b15\u03b21, promoting inflammatory cytokine production in chondrocytes.", "protein": "ANGPTL2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation of ANGPTL2 required for integrin binding.", "mechanism": "ANGPTL2-induced inflammation via integrin \u03b15\u03b21 contributes to cartilage degeneration.", "protein": "ANGPTL2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "medium", "disease": "Degenerative cartilage disorders", "glycan_involvement": "ITGBL1 is a glycoprotein; glycosylation may affect its inhibitory function.", "mechanism": "ITGBL1 inhibits integrin signaling and promotes chondrogenesis; its downregulation in osteoarthritis suggests a protective role.", "protein": "ITGBL1", "protein_enriched": { "function": "Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane,", "gene_name": "KIF13A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H1H9" }, "relationship_type": "protective", "source_pmcid": "PMC12395929" }, { "confidence": "medium", "disease": "Bone mineralization defects", "glycan_involvement": "FN1 is a glycoprotein; glycosylation affects ECM assembly.", "mechanism": "FN1 regulates osteoblast differentiation and mineralization via Wnt/\u03b2-catenin pathway; its dysregulation impairs bone formation.", "protein": "Fibronectin 1 (FN1)", "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "high", "disease": "Bone mineralization defects", "glycan_involvement": "Glycosylation required for integrin \u03b15\u03b21 function.", "mechanism": "Integrin \u03b15\u03b21 mediates osteogenic differentiation and mineralization; deficiency impairs bone formation.", "protein": "Integrin \u03b15\u03b21", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12395929" }, { "confidence": "medium", "disease": "Cartilage degeneration", "glycan_involvement": "Collagen II is a glycoprotein; glycosylation affects ECM structure.", "mechanism": "Collagen II is essential for cartilage ECM; integrin-mediated signaling maintains chondrocyte homeostasis, loss leads to degeneration.", "protein": "Collagen type II", "relationship_type": "protective", "source_pmcid": "PMC12395929" }, { "confidence": "high", "disease": "Liver injury/hepatitis", "glycan_involvement": "ALT is glycosylated, affecting stability and secretion.", "mechanism": "Elevated ALT indicates hepatocellular damage after high-dose extract exposure.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "high", "disease": "Liver injury/hepatitis", "glycan_involvement": "Glycosylation modulates GGT activity and membrane localization.", "mechanism": "Increased GGT signals liver or bile duct injury from extract toxicity.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "medium", "disease": "Liver injury/hepatitis", "glycan_involvement": "N-glycosylation affects albumin half-life and function.", "mechanism": "Dose-dependent rise in ALB in males suggests altered hepatic synthesis.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "medium", "disease": "Early mortality", "glycan_involvement": "Glycosylation may affect ALT stability.", "mechanism": "Low ALT in high-dose rats associated with increased frailty and short lifespan.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "Glycoproteins on erythrocyte surface influence RDW.", "mechanism": "Lowered RDW-SD in treated rats indicates reduced erythrocyte size variation, a marker for anemia.", "protein": "RDW-SD", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "low", "disease": "Inflammation", "glycan_involvement": "Glycosylation critical for IG effector functions.", "mechanism": "IG levels measured to assess immune response; no significant change observed.", "protein": "Immunoglobulin (IG)", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "low", "disease": "Renal toxicity", "glycan_involvement": "N-glycosylation affects renal clearance.", "mechanism": "ALB levels used to monitor renal function; no significant toxicity observed.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "high", "disease": "Drug-induced toxicity", "glycan_involvement": "Glycosylation may modulate ALT secretion.", "mechanism": "ALT elevation is a sensitive marker for herbal/drug-induced liver toxicity.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation impacts albumin filtration.", "mechanism": "Reduced kidney weight may signal hypertension risk; ALB used to monitor renal function.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12395998" }, { "confidence": "medium", "disease": "Candidiasis", "glycan_involvement": "Glycosylation essential for antifungal IG activity.", "mechanism": "Khaya anthotheca extract used for candidiasis; IG levels may reflect immune modulation.", "protein": "Immunoglobulin (IG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12395998" }, { "confidence": "high", "disease": "Metastatic urothelial carcinoma (mUC)", "glycan_involvement": "Nectin-4 is a glycoprotein; glycosylation may affect cell surface expression and antibody-drug conjugate binding.", "mechanism": "Nectin-4 is highly expressed on mUC cells and is targeted by enfortumab vedotin for selective cytotoxicity.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396074" }, { "confidence": "high", "disease": "Metastatic urothelial carcinoma (mUC)", "glycan_involvement": "PD-L1 glycosylation modulates its stability and immune recognition.", "mechanism": "PD-L1 is targeted by immune checkpoint inhibitors to restore anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396074" }, { "confidence": "medium", "disease": "Stevens-Johnson syndrome", "glycan_involvement": "Glycosylation may influence immune recognition and off-target effects.", "mechanism": "Targeting Nectin-4 by enfortumab vedotin may trigger immune-mediated skin toxicity.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "medium", "disease": "Interstitial pneumonia", "glycan_involvement": "Glycosylation may affect tissue distribution and immune response.", "mechanism": "Enfortumab vedotin targeting Nectin-4 may contribute to immune-mediated lung toxicity.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "low", "disease": "Anemia", "glycan_involvement": "Glycosylation status may influence off-target effects.", "mechanism": "Enfortumab vedotin may cause anemia as a treatment-related adverse event.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "low", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may affect renal tissue targeting.", "mechanism": "Renal impairment may be exacerbated by enfortumab vedotin targeting Nectin-4.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "low", "disease": "Stevens-Johnson syndrome", "glycan_involvement": "PD-L1 glycosylation may modulate immune response.", "mechanism": "Immune checkpoint inhibition may trigger immune-mediated skin toxicity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "low", "disease": "Interstitial pneumonia", "glycan_involvement": "PD-L1 glycosylation may modulate immune response.", "mechanism": "Immune checkpoint inhibition may trigger immune-mediated lung toxicity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "causal (adverse event)", "source_pmcid": "PMC12396074" }, { "confidence": "high", "disease": "Metastatic urothelial carcinoma (mUC)", "glycan_involvement": "Glycosylation may affect detection and antibody binding.", "mechanism": "Nectin-4 expression is used to select patients for enfortumab vedotin therapy.", "protein": "Nectin-4", "protein_enriched": { "function": "Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvir", "gene_name": "NECTIN4", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G20312EM", "G25451PN", "G47518TP", "G75983OB", "G83229XP", "G84452RH", "G80920RR" ], "uniprot_id": "Q96NY8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396074" }, { "confidence": "high", "disease": "Metastatic urothelial carcinoma (mUC)", "glycan_involvement": "Glycosylation may affect detection and immune evasion.", "mechanism": "PD-L1 expression is used to select patients for immune checkpoint inhibitor therapy.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396074" }, { "confidence": "high", "disease": "Hospital-acquired respiratory tract infection (HARTI)", "glycan_involvement": "CRP glycosylation modulates its stability and immune recognition.", "mechanism": "Elevated CRP indicates acute inflammation and is associated with increased risk of HARTI in ICU patients.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Hospital-acquired respiratory tract infection (HARTI)", "glycan_involvement": "Albumin glycosylation affects its half-life and transport function.", "mechanism": "Low serum albumin is associated with poor prognosis and higher risk of HARTI.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Hospital-acquired respiratory tract infection (HARTI)", "glycan_involvement": "Glycosylation of fibrin degradation products influences immune clearance.", "mechanism": "Elevated D-Dimer reflects coagulation activation and is linked to infection severity.", "protein": "D-Dimer", "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects prothrombin activation and stability.", "mechanism": "Altered prothrombin levels indicate coagulation dysfunction in sepsis.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Hospital-acquired respiratory tract infection (HARTI)", "glycan_involvement": "N-glycosylation modulates fibrinogen polymerization and immune response.", "mechanism": "High fibrinogen levels are associated with inflammation and infection risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Glycosylation affects GGT membrane localization and activity.", "mechanism": "Elevated GGT is indicative of hepatic dysfunction, which may predispose to infection.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Renal insufficiency", "glycan_involvement": "N-glycosylation patterns change in renal disease, affecting iron transport.", "mechanism": "Altered transferrin glycoforms are associated with renal dysfunction and infection risk.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "Fc N-glycosylation modulates IgG effector functions.", "mechanism": "IgG glycosylation status reflects immune competence and susceptibility to infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects AGP anti-inflammatory properties.", "mechanism": "AGP levels and glycoforms change during sepsis and infection.", "protein": "Alpha-1-acid glycoprotein (AGP)", "protein_enriched": { "function": "Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in ", "gene_name": "ORM1", "glycan_count": 239, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G06247RL", "G11314AS", "G15169WU", "G27947YN", "G28541PG", "G28681TP", "G35029YA", "G40834TG", "G45395BF", "G47518TP", "G57317CE", "G59626AS", "G66088HZ", "G70232NH", "G72291OX", "G72787SB", "G86182NS", "G94917XT", "G95678HJ", "G95865ZB", "G06356OH", "G11115RO", "G11629QQ", "G11911BT", "G12793SR", "G20425TQ", "G22140GZ", "G27322BI", "G32926LW", "G36131WL", "G39595FH", "G40926MX", "G41044JW", "G41882MT", "G44211QA", "G44753VC", "G48414YA", "G50045TK", "G52527GH", "G54682XF", "G59536GA", "G60033FS", "G64394MX", "G64527OM", "G70101JE", "G72797UR", "G78644BR", "G81263BG", "G82830MN", "G85144OK", "G86752LQ", "G92081HT", "G94854LT", "G99679NM", "G01650EU", "G02886BB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G08290VR", "G08918WF", "G10486CT", "G12341GU", "G13910DJ", "G14972EH", "G20706XG", "G22572EH", "G26330YA", "G27058EU", "G27126ED", "G37399XV", "G37509XX", "G37818NZ", "G37995HC", "G40574BA", "G41071NU", "G41840AI", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45504EY", "G47644PP", "G49018RC", "G49955PK", "G53075ES", "G54010QB", "G56307ZW", "G56518TU", "G57776ZS", "G57776ZU", "G58954YZ", "G62765YT", "G65184UU", "G66537LK", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72747WU", "G72790NZ", "G75983OB", "G76868JS", "G78787DI", "G79666IR", "G80075MS", "G81124ET", "G81637OR", "G83646BJ", "G84349RE", "G85269DF", "G85282JO", "G86795LJ", "G86880BF", "G90382BL", "G90659AW", "G92551JA", "G94470IW", "G96091TT", "G98129XB", "G98611JV", "G99668VU", "G01160VV", "G02528FI", "G03644CB", "G06290IR", "G07810QS", "G08293MJ", "G09831WQ", "G10819WX", "G10846ZT", "G11101UV", "G13191RB", "G14547CB", "G15664MX", "G18647XP", "G20528HD", "G23505EP", "G27915IV", "G29545VG", "G29580WD", "G30221QT", "G30248BL", "G30740WO", "G31028YV", "G31852PQ", "G31986NC", "G32788FZ", "G33416PL", "G35541EV", "G36670VW", "G37692EO", "G37868ZX", "G39471UU", "G43769HG", "G45526EA", "G46450MZ", "G46691LC", "G47012YE", "G49589RB", "G49755GI", "G49906RN", "G50120TH", "G50856PC", "G51941GC", "G52848YE", "G55132BD", "G56770VP", "G58087IP", "G59324HL", "G59924QI", "G60834IK", "G61256FT", "G62165AG", "G63040RU", "G64409MC", "G64751KD", "G65344XH", "G65414LI", "G67164EE", "G67506FN", "G68735SN", "G69521XL", "G69834CE", "G71463BG", "G72309KR", "G72951AH", "G73027HY", "G73028DK", "G73430PD", "G74381CZ", "G75006KF", "G77547TA", "G77669RF", "G78649WQ", "G80479JV", "G82443XX", "G83213GG", "G84225JN", "G85554PZ", "G85677PP", "G87123QX", "G87389XI", "G87399DK", "G92135MA", "G93656SY", "G93718GY", "G94665LC", "G95977AE", "G05933EN", "G07799LX", "G25079LO", "G28937TW", "G31153XO", "G31665QC", "G33791AF", "G34617SM", "G39446WN", "G47737VJ", "G53959KE", "G56784JY", "G60967DT", "G71560PC", "G73686WG", "G80669SJ", "G81128KB", "G83633GK", "G00776MW", "G22310AV", "G28916LJ", "G57581QG", "G66951WQ", "G84452RH", "G87108ET", "G91152KU", "G94239KE", "G97968CT" ], "uniprot_id": "P02763" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "medium", "disease": "Hospital-acquired respiratory tract infection (HARTI)", "glycan_involvement": "Glycosylation modulates haptoglobin clearance and immune interactions.", "mechanism": "Haptoglobin is an acute-phase reactant elevated in infection.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396645" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation may affect its stability and shedding, but not directly discussed.", "mechanism": "Elevated circulating ACE2 levels are associated with increased disease severity and mortality in sepsis.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "biomarker", "source_pmcid": "PMC12396652" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "ACE2 glycosylation may influence its renal localization and shedding.", "mechanism": "High serum ACE2 predicts increased risk of AKI within 48 hours in septic patients.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "biomarker", "source_pmcid": "PMC12396652" }, { "confidence": "high", "disease": "ICU mortality", "glycan_involvement": "Glycosylation status may affect ACE2's circulatory half-life.", "mechanism": "High ACE2 is an independent predictor of ICU mortality in sepsis.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "biomarker", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "ACE2/Ang-(1\u20137) axis exerts cardioprotective effects in experimental models.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "protective", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may modulate receptor activity.", "mechanism": "ACE2/Ang-(1\u20137) axis reduces inflammation and injury in myocardial infarction models.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "protective", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may affect ACE2's enzymatic activity.", "mechanism": "ACE2 prevents pancreatic beta-cell dysfunction and improves glycemia in diabetic mice.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may influence ACE2 stability in renal tissue.", "mechanism": "Reduced ACE2 expression is linked to progression of renal dysfunction.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal/protective", "source_pmcid": "PMC12396652" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Both ACE2 and viral spike are glycoproteins; glycosylation is critical for interaction.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2 via spike glycoprotein binding.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Multi-organ dysfunction", "glycan_involvement": "Glycosylation may affect ACE2's susceptibility to viral binding and shedding.", "mechanism": "Downregulation of ACE2 after viral infection leads to RAS imbalance and multi-organ dysfunction.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC12396652" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation may be required for ACE2's renal protective function.", "mechanism": "ACE2 and Ang-(1\u20137) exert renoprotective effects by improving renal blood flow and filtration.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "protective", "source_pmcid": "PMC12396652" }, { "confidence": "high", "disease": "Platelet activation (PA)", "glycan_involvement": "P-selectin is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated sP-selectin reflects increased platelet activation in PLHIV.", "protein": "Soluble P-selectin", "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Immune activation (IA)", "glycan_involvement": "CD14 is glycosylated; glycan structures influence its shedding and immune signaling.", "mechanism": "Elevated sCD14 indicates monocyte activation and systemic inflammation in PLHIV.", "protein": "Soluble CD14", "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Immune activation (IA)", "glycan_involvement": "CD69 is a glycoprotein; glycosylation modulates its surface expression.", "mechanism": "CD69 expression on T-cells marks acute immune activation in HIV infection.", "protein": "CD69", "protein_enriched": { "function": "Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells ", "gene_name": "CD69", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Immune activation (IA)", "glycan_involvement": "CD38 is glycosylated; glycan modifications affect receptor function.", "mechanism": "CD38/HLA-DR co-expression on T-cells marks chronic immune activation in HIV.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Immune activation (IA)", "glycan_involvement": "HLA-DR is heavily glycosylated; glycosylation impacts antigen presentation.", "mechanism": "HLA-DR co-expression with CD38 on T-cells is a marker of chronic activation in HIV.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Immune activation (IA)", "glycan_involvement": "PD-1 is glycosylated; glycan structures regulate its inhibitory function.", "mechanism": "PD-1 expression on T-cells indicates T-cell exhaustion in chronic HIV infection.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "medium", "disease": "Non-AIDS complications (e.g., cardiovascular disease)", "glycan_involvement": "Glycosylation of P-selectin modulates its interaction with ligands and endothelium.", "mechanism": "Platelet activation (via sP-selectin) contributes to cardiovascular risk in PLHIV.", "protein": "Soluble P-selectin", "relationship_type": "causal", "source_pmcid": "PMC12396663" }, { "confidence": "medium", "disease": "Non-AIDS complications (e.g., cardiovascular disease)", "glycan_involvement": "Glycosylation affects CD14's immune signaling and shedding.", "mechanism": "Chronic monocyte activation (sCD14) is linked to inflammation and non-AIDS morbidity.", "protein": "Soluble CD14", "relationship_type": "causal", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation modulates CD69's surface stability and immune signaling.", "mechanism": "CD69+ T-cells are elevated in HIV infection, reflecting ongoing immune activation.", "protein": "CD69", "protein_enriched": { "function": "Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells ", "gene_name": "CD69", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00912UN", "G48414YA", "G49108TO" ], "uniprot_id": "Q07108" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "PD-1 glycosylation regulates its inhibitory signaling.", "mechanism": "PD-1+ T-cells indicate exhaustion and impaired immune response in HIV.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC12396663" }, { "confidence": "high", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "AST and ALT are glycoproteins; glycosylation may affect their stability and secretion, but not directly discussed.", "mechanism": "Low AST/ALT ratio in early pregnancy is independently associated with increased risk of GDM, reflecting hepatic metabolic dysfunction and insulin resistance.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "medium", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence its serum levels.", "mechanism": "Elevated ALT levels are associated with increased risk of GDM, possibly due to impaired hepatic gluconeogenesis and glucose metabolism.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "low", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its release.", "mechanism": "AST levels may reflect muscle or hepatic injury; its independent predictive value for GDM is debated.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "high", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "Indirect; glycosylation may modulate enzyme activity.", "mechanism": "Low AST/ALT ratio is inversely associated with T2DM risk, indicating hepatic insulin resistance.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Indirect; glycosylation may affect enzyme secretion.", "mechanism": "Low AST/ALT ratio predicts NAFLD occurrence, reflecting hepatic steatosis and mild injury.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "medium", "disease": "Insulin resistance (IR)", "glycan_involvement": "Hepatokines are glycoproteins; glycosylation is critical for their secretion and activity.", "mechanism": "Hepatocyte injury triggers hepatokine release, inducing peripheral insulin resistance by interfering with insulin signaling.", "protein": "Hepatokines", "relationship_type": "causal", "source_pmcid": "PMC12396687" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Indirect; glycosylation may affect AST release from cardiac tissue.", "mechanism": "High AST/ALT ratio is associated with increased cardiovascular risk, reflecting myocardial injury.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Indirect; glycosylation may modulate enzyme function.", "mechanism": "Low AST/ALT ratio is a predictor of metabolic syndrome in Asian populations.", "protein": "AST/ALT ratio", "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus (T2DM)", "glycan_involvement": "ALT glycosylation may affect its serum stability.", "mechanism": "Elevated ALT is associated with increased T2DM risk, reflecting hepatic dysfunction.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12396687" }, { "confidence": "low", "disease": "Gestational diabetes mellitus (GDM)", "glycan_involvement": "Glycosylation is essential for hepatokine function and signaling.", "mechanism": "Hepatocyte injury and hepatokine release may contribute to systemic insulin resistance and GDM development.", "protein": "Hepatokines", "relationship_type": "causal", "source_pmcid": "PMC12396687" }, { "confidence": "high", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function in inflammation.", "mechanism": "Elevated CRP reflects systemic inflammation, correlates with poor prognosis and recurrence.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397315" }, { "confidence": "high", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "Albumin glycosylation modulates its half-life and anti-inflammatory properties.", "mechanism": "Low serum albumin is associated with poor prognosis and higher recurrence risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397315" }, { "confidence": "high", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "MDM2 amplification drives tumorigenesis and may promote a pro-inflammatory microenvironment.", "protein": "MDM2", "protein_enriched": { "function": "E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). 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Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "causal", "source_pmcid": "PMC12397315" }, { "confidence": "medium", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "Glycosylation regulates MMP secretion and activity.", "mechanism": "MMPs remodel extracellular matrix, facilitating invasion and metastasis.", "protein": "Matrix metalloproteinases (MMPs)", "relationship_type": "causal", "source_pmcid": "PMC12397315" }, { "confidence": "medium", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "IL-6 glycosylation influences stability and receptor binding.", "mechanism": "IL-6 drives inflammation and tumor-promoting immune suppression.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC12397315" }, { "confidence": "medium", "disease": "Primary retroperitoneal liposarcoma (PRPLS)", "glycan_involvement": "TNF-\u03b1 glycosylation affects secretion and bioactivity.", "mechanism": "TNF-\u03b1 promotes inflammatory microenvironment and tumor progression.", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC12397315" }, { "confidence": "high", "disease": "Liver dysfunction", "glycan_involvement": "CRP glycosylation is critical for its function and clearance.", "mechanism": "Elevated CRP indicates hepatic acute-phase response and systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397315" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "AChE is glycosylated, which affects its stability and localization in neurons.", "mechanism": "AChE degrades acetylcholine, leading to reduced neurotransmission and cognitive decline; inhibition improves symptoms.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397321" }, { "confidence": "medium", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates AChE activity and secretion.", "mechanism": "Elevated AChE activity correlates with cholinergic neuron loss and dementia severity.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397321" }, { "confidence": "low", "disease": "Glaucoma", "glycan_involvement": "Glycosylation may affect AChE pharmacodynamics in ocular tissues.", "mechanism": "AChE inhibitors are used to increase acetylcholine and reduce intraocular pressure.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397321" }, { "confidence": "low", "disease": "Myasthenia gravis", "glycan_involvement": "Glycosylation influences AChE localization at neuromuscular junctions.", "mechanism": "AChE inhibitors improve neuromuscular transmission.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397321" }, { "confidence": "low", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation may affect AChE function in the CNS.", "mechanism": "Cholinesterase inhibitors may modulate cognitive symptoms.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397321" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation can regulate SOD stability and activity.", "mechanism": "Reduced SOD activity indicates oxidative stress in AD brains.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397321" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects GPx secretion and activity.", "mechanism": "Decreased GPx activity reflects impaired antioxidant defense in AD.", "protein": "Glutathione peroxidase (GPx)", "protein_enriched": { "function": "Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles", "gene_name": "Gsta4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24472" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397321" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates catalase stability and function.", "mechanism": "Lower catalase activity is associated with increased oxidative damage in AD.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397321" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Altered glycosylation may affect AChE distribution and activity in AD.", "mechanism": "Loss of cholinergic neurons and increased AChE activity contribute to AD pathogenesis.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "causal", "source_pmcid": "PMC12397321" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation status may influence drug binding and efficacy.", "mechanism": "AChE inhibition by letrozole-loaded SLNs provides neuroprotection and improves cognitive function in AD rat model.", "protein": "Acetylcholinesterase (AChE)", "protein_enriched": { "function": "Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis", "gene_name": "ACHE", "glycan_count": 2, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83460ZZ", "G41247ZX" ], "uniprot_id": "P22303" }, "relationship_type": "protective", "source_pmcid": "PMC12397321" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is heavily glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Spike mediates viral entry via ACE2 binding and membrane fusion.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutations may alter glycosylation sites, affecting antigenicity and antibody recognition.", "mechanism": "Spike mutations (e.g., L5F, A27P, F375S, A376T, A701V, L822F, K786N, H1271L) track variant emergence and immune escape.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12397351" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans modulate accessibility of neutralizing epitopes.", "mechanism": "Spike is the primary target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397351" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutations near glycosylation sites may enhance immune escape.", "mechanism": "Spike mutations (e.g., L452R, F486V, S494P, T572I, P681H) increase breakthrough infection rates.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation in S1/S2 region influences protease accessibility.", "mechanism": "Mutations in the activation corridor (A701V, L822F, K786N) affect proteolytic priming and fusion efficiency.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycans on NTD shield key epitopes.", "mechanism": "N-terminal domain mutations (A27P, F59S, K202N, P272S) modulate antigenic surface and antibody escape.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycans near RBD affect receptor binding and immune recognition.", "mechanism": "RBD shoulder mutations (F375S, A376T) alter RBD conformation and ACE2 engagement.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Cytosolic tail is not glycosylated but impacts spike density on virions.", "mechanism": "Cytosolic tail mutation (H1271L) may affect spike incorporation into virions.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Altered glycosylation may facilitate immune evasion.", "mechanism": "Spike mutations in vaccinated individuals suggest immune-driven selection of escape variants.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12397351" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield changes can signal emergence of new variants.", "mechanism": "Spike mutation profiling enables surveillance of immune-escape lineages.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC12397351" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "PEDF is a secreted glycoprotein; glycosylation likely required for secretion and stability.", "mechanism": "PEDF inhibits NF-\u03baB signaling via PPAR\u03b3, reducing inflammatory cytokines and protecting corneal tissue.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "IL-36\u03b3 is a glycoprotein; glycosylation may affect secretion and receptor binding.", "mechanism": "IL-36\u03b3 reduces inflammation, interacts with PEDF, and its knockdown increases inflammatory cytokines.", "protein": "IL-36\u03b3 (Interleukin-36 gamma)", "protein_enriched": { "function": "Immune regulatory cytokine that acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. Signaling can occur via two mechanisms, intracellularly thr", "gene_name": "IL37", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZH6" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC12397381" }, { "confidence": "medium", "disease": "Dry eye syndrome", "glycan_involvement": "Glycosylation supports PEDF's anti-inflammatory function.", "mechanism": "PEDF reduces IL-1\u03b2 and TNF-\u03b1 via NF-\u03baB pathway modulation.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "protective", "source_pmcid": "PMC12397381" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation required for PEDF stability and function.", "mechanism": "PEDF regulates PPAR\u03b3 and blocks NF-\u03baB activation, inhibiting podocyte apoptosis and mesangial cell damage.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "protective", "source_pmcid": "PMC12397381" }, { "confidence": "medium", "disease": "Retinal vascular disease", "glycan_involvement": "Glycosylation important for PEDF's anti-angiogenic activity.", "mechanism": "PEDF inhibits neovascularization and inflammation in retinal tissue.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "protective", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "Glycosylation may affect PEDF detection and stability.", "mechanism": "PEDF expression decreases after CA infection; low PEDF correlates with increased inflammation.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "biomarker", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "Glycosylation may affect IL-36\u03b3 detection and activity.", "mechanism": "IL-36\u03b3 expression increases after CA infection; high IL-36\u03b3 correlates with inflammatory response.", "protein": "IL-36\u03b3 (Interleukin-36 gamma)", "protein_enriched": { "function": "Immune regulatory cytokine that acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. Signaling can occur via two mechanisms, intracellularly thr", "gene_name": "IL37", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZH6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "Glycosylation status not altered by miR-204-5p, but reduced PEDF impacts anti-inflammatory function.", "mechanism": "miR-204-5p directly binds PEDF mRNA, suppressing PEDF and exacerbating inflammation.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "causal", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "Glycosylation status not altered by miR-204-5p, but reduced IL-36\u03b3 impacts anti-inflammatory function.", "mechanism": "miR-204-5p suppresses IL-36\u03b3 mRNA, increasing inflammation.", "protein": "IL-36\u03b3 (Interleukin-36 gamma)", "protein_enriched": { "function": "Immune regulatory cytokine that acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. Signaling can occur via two mechanisms, intracellularly thr", "gene_name": "IL37", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZH6" }, "relationship_type": "causal", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Candida albicans keratitis", "glycan_involvement": "Therapeutic PEDF likely requires proper glycosylation for efficacy.", "mechanism": "Exogenous PEDF administration alleviates corneal inflammation and reduces fungal load.", "protein": "PEDF (Pigment Epithelium-Derived Factor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397381" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation (Gal-GalNAc) on cancer cell surface proteins is the receptor for Fap2.", "mechanism": "Fap2 binds Gal-GalNAc on colon cancer cells, promoting tumor colonization and growth.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Detection of Gal-GalNAc and Fap2 presence correlates with CRC.", "mechanism": "Fusobacterium nucleatum (Fn) and Fap2 are overrepresented in CRC patient microbiomes.", "protein": "Fap2", "relationship_type": "biomarker", "source_pmcid": "PMC12397386" }, { "confidence": "high", "disease": "Metastasis", "glycan_involvement": "Fap2 binds TIGIT, which is N-glycosylated; interaction requires TIGIT glycosylation.", "mechanism": "Fap2-mediated immune cell deactivation via TIGIT promotes tumor immune evasion and metastasis.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "medium", "disease": "Chemotherapeutic resistance", "glycan_involvement": "Fap2-Gal-GalNAc interaction anchors Fn to tumor cells.", "mechanism": "Fn colonization via Fap2 may contribute to resistance by protecting tumor cells from immune clearance.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Likely via glycan-mediated adhesion, though specific glycan not detailed.", "mechanism": "Fn and Fap2 shown to drive breast cancer growth.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "medium", "disease": "Preterm birth", "glycan_involvement": "Gal-GalNAc present in placenta may serve as Fap2 receptor.", "mechanism": "Fn associated with preterm birth, possibly via Fap2-mediated placental colonization.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "medium", "disease": "Stillbirth", "glycan_involvement": "Gal-GalNAc as placental glycan receptor for Fap2.", "mechanism": "Fn and Fap2 implicated in stillbirth via placental colonization.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "low", "disease": "Periodontal disease", "glycan_involvement": "Glycan-mediated adhesion probable but not specified.", "mechanism": "Fn and Fap2 associated with periodontal disease, likely via adhesion to oral epithelial cells.", "protein": "Fap2", "relationship_type": "causal", "source_pmcid": "PMC12397386" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "N-glycosylation of TIGIT required for Fap2 binding.", "mechanism": "TIGIT on immune cells is deactivated by Fap2, suggesting TIGIT blockade may restore immune function.", "protein": "TIGIT", "protein_enriched": { "function": "Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon", "gene_name": "TIGIT", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q495A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397386" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "O-glycosylation of surface proteins with Gal-GalNAc.", "mechanism": "Gal-GalNAc is abundant and specific for colon cancer cells; serves as a biomarker and Fap2 receptor.", "protein": "Gal-GalNAc", "relationship_type": "biomarker", "source_pmcid": "PMC12397386" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "vWF is heavily glycosylated; glycosylation affects its multimerization and platelet binding.", "mechanism": "vWF degradation is promoted by prostaglandin E2, reducing thrombosis risk; impaired degradation may contribute to clot formation.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Glycosylation modulates vWF clearance and activity.", "mechanism": "Elevated vWF levels indicate endothelial dysfunction and increased risk of thrombosis in COVID-19.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "ApoA is glycosylated; glycosylation may affect lipid transport and immune modulation.", "mechanism": "Decreased ApoA levels are associated with increased severity of COVID-19.", "protein": "Apolipoprotein A (ApoA)", "relationship_type": "biomarker", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may influence ApoA's anti-inflammatory properties.", "mechanism": "Lower ApoA levels correlate with higher thrombosis risk in COVID-19 patients.", "protein": "Apolipoprotein A (ApoA)", "relationship_type": "biomarker", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection", "glycan_involvement": "ApoB glycosylation affects lipoprotein structure and function.", "mechanism": "Reduced ApoB levels are observed in severe COVID-19 cases.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation may modulate ApoB's role in lipid metabolism and vascular health.", "mechanism": "Lower ApoB levels are linked to increased thrombosis risk in COVID-19.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "biomarker", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation regulates vWF's interaction with platelets and vessel wall.", "mechanism": "vWF contributes to platelet adhesion and aggregation, promoting cardiovascular complications.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation may affect ApoA's anti-atherogenic functions.", "mechanism": "Higher ApoA levels are protective against cardiovascular disease; reduction increases risk.", "protein": "Apolipoprotein A (ApoA)", "relationship_type": "protective", "source_pmcid": "PMC12397397" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation impacts ApoB's stability and interaction with arterial wall.", "mechanism": "ApoB is a key component of LDL; its glycosylation status influences plaque formation.", "protein": "Apolipoprotein B (ApoB)", "relationship_type": "causal", "source_pmcid": "PMC12397397" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects vWF's endothelial interactions.", "mechanism": "COX-related lipid molecules, including vWF, can lead to endothelial dysfunction and hypertension.", "protein": "von Willebrand factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC12397397" }, { "confidence": "high", "disease": "Rift Valley fever (RVF)", "glycan_involvement": "Gn is a glycoprotein; glycosylation is required for proper folding, immune evasion, and infectivity.", "mechanism": "Gn mediates viral entry and is essential for RVFV infectivity and pathogenesis.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Rift Valley fever (RVF)", "glycan_involvement": "Gc is glycosylated; glycosylation affects fusion activity and immune recognition.", "mechanism": "Gc is required for membrane fusion and viral entry into host cells.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Abortion in sheep", "glycan_involvement": "Glycosylation of Gn facilitates viral spread in reproductive tissues.", "mechanism": "Gn-dependent RVFV infection of placental tissues leads to abortion.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Abortion in sheep", "glycan_involvement": "Gc glycosylation is necessary for infectivity in reproductive tissues.", "mechanism": "Gc-dependent viral entry into placental and foetal cells causes reproductive failure.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Foetal death/malformation", "glycan_involvement": "Gn glycosylation supports viral tropism for foetal cells.", "mechanism": "RVFV Gn enables infection of foetal tissues, resulting in death or malformation.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Foetal death/malformation", "glycan_involvement": "Gc glycosylation is required for efficient infection of foetal tissues.", "mechanism": "Gc mediates viral fusion in foetal cells, contributing to pathology.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Liver necrosis", "glycan_involvement": "Gn glycosylation enhances viral infectivity in liver cells.", "mechanism": "Gn-dependent RVFV infection of hepatocytes leads to necrotic lesions.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Liver necrosis", "glycan_involvement": "Gc glycosylation is critical for hepatocyte infection.", "mechanism": "Gc enables RVFV entry into hepatocytes, causing necrosis.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Rift Valley fever (RVF)", "glycan_involvement": "Glycosylation may affect antigenicity and vaccine efficacy.", "mechanism": "Gn is targeted by neutralizing antibodies induced by vaccination (40Fp8), conferring protection.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Rift Valley fever (RVF)", "glycan_involvement": "Gc glycosylation influences immune recognition and vaccine effectiveness.", "mechanism": "Gc is targeted by vaccine-induced immune responses, contributing to protection.", "protein": "Gc", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397403" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "B3GAT1 catalyzes glycosaminoglycan chain extension; altered glycosylation modulates tumor cell behavior.", "mechanism": "Genetically decreased B3GAT1 levels increase prostate cancer risk; involved in glycosaminoglycan biosynthesis affecting cell adhesion and signaling.", "protein": "B3GAT1 (Beta-1,3-glucuronyltransferase 1)", "protein_enriched": { "function": "Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1) (PubMed:19587235, PubMed:23359570, PubMed:25279697, PubMed:25279699). Transfers a glucuronic acid (GlcA) residue", "gene_name": "B4GAT1", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G62765YT", "G36379GD", "G83229XP", "G49108TO" ], "uniprot_id": "O43505" }, "relationship_type": "causal", "source_pmcid": "PMC12397405" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "LTK is a glycoprotein receptor; glycosylation may affect receptor function and signaling.", "mechanism": "LTK variants causally affect diabetes risk, possibly via insulin signaling pathways (PIK3R1 interaction).", "protein": "LTK (Leukocyte receptor tyrosine kinase)", "protein_enriched": { "function": "Receptor with a tyrosine-protein kinase activity (PubMed:10445845, PubMed:20548102, PubMed:30061385). Following activation by ALKAL1 or ALKAL2 ligands at the cell surface, transduces an extracellular ", "gene_name": "LTK", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "P29376" }, "relationship_type": "causal", "source_pmcid": "PMC12397405" }, { "confidence": "medium", "disease": "Age-related macular degeneration", "glycan_involvement": "Glycosylation may regulate protein stability and localization in retina.", "mechanism": "Higher NIF3L1 levels decrease risk; involved in transcriptional regulation in retinal cells.", "protein": "NIF3L1 (NGG1 interacting factor 3 like 1)", "relationship_type": "protective", "source_pmcid": "PMC12397405" }, { "confidence": "low", "disease": "Testosterone level alteration", "glycan_involvement": "Potential glycosylation may affect enzyme activity.", "mechanism": "NTAQ1 levels associated with testosterone; mechanism unclear.", "protein": "NTAQ1 (N-terminal glutamine amidase 1)", "protein_enriched": { "function": "Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N)", "gene_name": "QTRT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BXR0" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397405" }, { "confidence": "medium", "disease": "Epigenetic age acceleration", "glycan_involvement": "Glycosylation may modulate protein function in adipogenesis and aging.", "mechanism": "AAMDC levels linked to DNA methylation-based age acceleration.", "protein": "AAMDC (Adipogenesis Associated Mth938 Domain Containing protein)", "relationship_type": "causal", "source_pmcid": "PMC12397405" }, { "confidence": "low", "disease": "Systolic blood pressure", "glycan_involvement": "Glycosylation may affect chromatin remodeling activity.", "mechanism": "BCL7A levels associated with blood pressure regulation.", "protein": "BCL7A (BAF Chromatin Remodelling Complex Subunit BCL7A)", "protein_enriched": { "function": "May act as a GTPase-activating protein for Rab family protein(s)", "gene_name": "TBC1D30", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y2I9" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397405" }, { "confidence": "low", "disease": "Parental longevity", "glycan_involvement": "Glycosylation may influence protein stability.", "mechanism": "COMMD10 levels associated with maternal attained age.", "protein": "COMMD10 (COMM Domain-Containing Protein 10)", "relationship_type": "biomarker", "source_pmcid": "PMC12397405" }, { "confidence": "medium", "disease": "Lupus erythematosus", "glycan_involvement": "Fc receptor glycosylation modulates immune complex binding.", "mechanism": "FCGR2B variants implicated in autoimmune disease risk.", "protein": "FCGR2B (Immunoglobulin G Fc Gamma receptor IIb)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12397405" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Fucosidase activity alters glycan structures on immune cells.", "mechanism": "FUCA1 levels associated with asthma risk.", "protein": "FUCA1 (Alpha-L-fucosidase 1)", "relationship_type": "biomarker", "source_pmcid": "PMC12397405" }, { "confidence": "low", "disease": "Cardiac arrhythmia", "glycan_involvement": "CFH glycosylation affects complement regulation.", "mechanism": "CFH levels associated with arrhythmia risk.", "protein": "CFH (Complement Factor H)", "relationship_type": "biomarker", "source_pmcid": "PMC12397405" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Fibronectin is a heavily glycosylated protein; glycosylation modulates its cell adhesion properties and interaction with integrins.", "mechanism": "Hypomethylation of FN1-associated DMRs in EV-DNA correlates with increased cell adhesion and migration in cancer.", "protein": "FN1 (Fibronectin)", "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "EGFR N-glycosylation affects receptor stability and ligand binding, influencing tumor cell signaling.", "mechanism": "EV-DNA hypomethylation near EGFR is associated with enhanced cell migration and autocrine signaling in cancer progression.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CXCR4 glycosylation regulates receptor trafficking and ligand interaction, impacting metastasis.", "mechanism": "EV-DNA hypomethylation near CXCR4 is linked to increased metastatic potential via chemokine signaling.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Integrin alpha-5 glycosylation modulates integrin activation and cell-matrix interactions.", "mechanism": "EV-DNA methylation changes near ITGA5 are associated with altered cell adhesion and migration.", "protein": "ITGA5", "protein_enriched": { "function": "Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct ", "gene_name": "ITGA5", "glycan_count": 121, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G49108TO", "G00912UN", "G04657PL", "G08918WF", "G27058EU", "G27126ED", "G45395BF", "G46503DX", "G46691LC", "G55220VL", "G57776ZS", "G80075MS", "G81315DD", "G84452RH", "G90659AW", "G11629QQ", "G48905WL", "G55132BD", "G22768VO", "G09724ZC", "G64481DJ", "G83473RC", "G06356OH", "G15169WU", "G22310AV", "G31916IQ", "G47518TP", "G48414YA", "G52527GH", "G55412XP", "G10404TD", "G62765YT", "G80920RR", "G93718GY", "G02815KT", "G05049YU", "G28541PG", "G31852PQ", "G41247ZX", "G62461SM", "G72747WU", "G41891LD", "G13694XX", "G14796IU", "G33791AF", "G47748JZ", "G56784JY", "G81263BG", "G81637OR", "G89865VY", "G22573RC", "G12604EW", "G14994KB", "G18647XP", "G25703UN", "G34617SM", "G40834TG", "G41071NU", "G43223CG", "G45495MK", "G57818FI", "G59324HL", "G60033FS", "G61627IG", "G70441OD", "G70619PT", "G75568BH", "G75983OB", "G79666IR", "G87123QX", "G90382BL", "G92135MA", "G57321FI", "G06110VR", "G11041DA", "G11870QZ", "G12398HZ", "G14996IQ", "G16529MG", "G17689DH", "G20425TQ", "G23863VK", "G25520XG", "G29880MM", "G36191CD", "G39188ZX", "G39595FH", "G45209NR", "G45359RY", "G45560HM", "G48954CA", "G50045TK", "G50489VC", "G53752TA", "G56318NV", "G56549DH", "G56749GV", "G63889NK", "G66088HZ", "G69834CE", "G72291OX", "G72797UR", "G73759SD", "G77252PU", "G78059CC", "G79809MM", "G80537QW", "G80966KZ", "G84467IZ", "G86357DX", "G86696LV", "G86753CK", "G90093AU", "G91365ZQ", "G91413ZX", "G91636VS", "G91905FJ", "G92574YO", "G94531EZ", "G98366ZJ", "G99074EO" ], "uniprot_id": "P08648" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "EPHA2 glycosylation affects receptor localization and signaling.", "mechanism": "EV-DNA methylation changes near EPHA2 are linked to cell communication and migration.", "protein": "EPHA2", "protein_enriched": { "function": "Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The s", "gene_name": "EPHA2", "glycan_count": 8, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G57321FI", "G41071NU", "G02815KT", "G05724UK", "G10256JP", "G14669DU", "G28681TP", "G49108TO" ], "uniprot_id": "P29317" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "SRC glycosylation may regulate kinase activity and protein interactions.", "mechanism": "EV-DNA methylation changes near SRC are associated with altered cell signaling in cancer.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "YES1 glycosylation may affect kinase localization and function.", "mechanism": "EV-DNA methylation changes near YES1 reflect abnormal tyrosine kinase signaling in tumors.", "protein": "YES1", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by recepto", "gene_name": "YES1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07947" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "TSG101 is glycosylated, which may affect EV biogenesis.", "mechanism": "TSG101 is an EV marker; its presence in EVs is used to confirm exosomal origin in cancer samples.", "protein": "TSG101", "protein_enriched": { "function": "Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicu", "gene_name": "TSG101", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q99816" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "CD63 glycosylation modulates exosome formation and cargo sorting.", "mechanism": "CD63 is an EV marker; its detection confirms exosomal characteristics in cancer-derived EVs.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "HSP70 glycosylation may influence protein stability and EV packaging.", "mechanism": "HSP70 is an EV marker; its presence supports exosomal origin in cancer samples.", "protein": "HSP70", "protein_enriched": { "function": "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteol", "gene_name": "HSPA1A", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G82830MN", "G49108TO" ], "uniprot_id": "P0DMV8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397421" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Potential regulation via glycosylation affecting transcriptional activity", "mechanism": "Promotes lipid accumulation and progression to hepatocellular carcinoma", "protein": "E2F1", "protein_enriched": { "function": "Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved i", "gene_name": "E2F1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01094" }, "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "high", "disease": "Nonalcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate TP53 stability and function", "mechanism": "Regulates inflammatory responses and cell death in liver disease progression", "protein": "TP53", "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Parkinson's disease (PD)", "glycan_involvement": "Glycosylation can affect NF-\u03baB1 nuclear translocation", "mechanism": "Associated with neuroinflammation and PD pathogenesis", "protein": "NF-\u03baB1", "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Parkinson's disease (PD)", "glycan_involvement": "O-glycosylation modulates Sp1 DNA binding", "mechanism": "Regulates genes involved in PD pathogenesis", "protein": "Sp1", "protein_enriched": { "function": "Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a larg", "gene_name": "SP1", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P08047" }, "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Huntington's disease (HD)", "glycan_involvement": "Glycosylation may affect JUN stability", "mechanism": "Involved in neuronal cell death and HD pathogenesis", "protein": "JUN", "protein_enriched": { "function": "Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcri", "gene_name": "JUN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P05412" }, "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Parkinson's disease (PD)", "glycan_involvement": "Glycosylation may regulate ETS-1 activity and localization", "mechanism": "ETS-1 overexpression disrupts dopamine receptor balance, reduces GABA enzyme levels, and promotes cell death", "protein": "ETS-1", "protein_enriched": { "function": "Transcription factor (PubMed:10698492, PubMed:11909962). Directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts (PubMed:20378371). May contro", "gene_name": "ETS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14921" }, "relationship_type": "modulator", "source_pmcid": "PMC12397437" }, { "confidence": "high", "disease": "Parkinson's disease (PD)", "glycan_involvement": "N-glycosylation affects TH stability and activity", "mechanism": "TH is the rate-limiting enzyme in dopamine production, reduced in PD", "protein": "Tyrosine hydroxylase (TH)", "relationship_type": "biomarker", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Parkinson's disease (PD)", "glycan_involvement": "Glycosylation modulates enzyme activity", "mechanism": "Reduced GABA enzyme levels contribute to motor dysfunction", "protein": "GABA-producing enzyme (GAD1/GAD2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12397437" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation may affect E2F1-mediated transcription", "mechanism": "Promotes malignant progression from NAFLD/NASH", "protein": "E2F1", "protein_enriched": { "function": "Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved i", "gene_name": "E2F1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01094" }, "relationship_type": "causal", "source_pmcid": "PMC12397437" }, { "confidence": "low", "disease": "Huntington's disease (HD)", "glycan_involvement": "Potential glycosylation-dependent regulation of ETS-1", "mechanism": "ETS-1 gene group associated with voluntary movement spectrum in HD", "protein": "ETS-1", "protein_enriched": { "function": "Transcription factor (PubMed:10698492, PubMed:11909962). Directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts (PubMed:20378371). May contro", "gene_name": "ETS1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14921" }, "relationship_type": "modulator", "source_pmcid": "PMC12397437" }, { "confidence": "high", "disease": "Hypoalbuminemia", "glycan_involvement": "N-glycosylation affects albumin stability and serum half-life.", "mechanism": "Low serum albumin reflects impaired hepatic synthetic function post portal vein stenosis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "high", "disease": "Impaired coagulation", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "Reduced prothrombin activity (high INR) indicates liver dysfunction due to portal vein occlusion.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Impaired coagulation", "glycan_involvement": "Glycosylation modulates platelet adhesion and aggregation.", "mechanism": "Low platelet count and function contribute to bleeding risk in portal hypertension.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "N-glycosylation affects ALP activity and secretion.", "mechanism": "Elevated ALP reflects cholestasis and hepatic injury post portal vein occlusion.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "high", "disease": "Acute liver failure", "glycan_involvement": "N-glycosylation required for membrane localization and activity.", "mechanism": "Elevated GGT indicates biliary dysfunction and hepatic injury.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may affect stability and serum detection.", "mechanism": "Elevated AST signals hepatocellular damage due to ischemia.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Glycosylation may affect stability and serum detection.", "mechanism": "Elevated ALT is a marker of hepatocellular injury.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Portal vein stenosis/occlusion", "glycan_involvement": "N-glycosylation impacts albumin secretion.", "mechanism": "Serum albumin levels decrease in portal vein stenosis due to impaired hepatic synthesis.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation modulates platelet-endothelial interactions.", "mechanism": "Platelet dysfunction and low count contribute to bleeding risk in portal hypertension.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12397468" }, { "confidence": "medium", "disease": "Ascites", "glycan_involvement": "N-glycosylation affects albumin's oncotic pressure function.", "mechanism": "Low albumin contributes to fluid accumulation (ascites) in portal hypertension.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "causal", "source_pmcid": "PMC12397468" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "EGFR is a heavily N-glycosylated glycoprotein; glycosylation affects ligand binding and stability.", "mechanism": "EGFR overexpression drives proliferation, survival, and resistance in HNSCC; stabilized by UBASH3B.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Head and Neck Squamous Cell Carcinoma (HNSCC)", "glycan_involvement": "Indirect; UBASH3B regulates glycoprotein EGFR turnover.", "mechanism": "UBASH3B overexpression stabilizes EGFR, enhances oncogenic signaling, and correlates with poor prognosis.", "protein": "UBASH3B", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Triple-Negative Breast Cancer (TNBC)", "glycan_involvement": "Indirect; EGFR glycosylation status may affect UBASH3B-mediated stabilization.", "mechanism": "UBASH3B promotes invasion and metastasis by downregulating miR-200a and stabilizing EGFR.", "protein": "UBASH3B", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "Indirect; CBL and RTKs are glycoproteins.", "mechanism": "UBASH3B inactivates CBL, leading to persistent RTK signaling and myeloid proliferation.", "protein": "UBASH3B", "relationship_type": "causal", "source_pmcid": "PMC12398026" }, { "confidence": "medium", "disease": "Lung Adenocarcinoma (LUAD)", "glycan_involvement": "No direct glycan involvement reported.", "mechanism": "UBASH3B dephosphorylates MRPL12, maintaining mitochondrial metabolism and suppressing tumor progression.", "protein": "UBASH3B", "relationship_type": "protective/biomarker", "source_pmcid": "PMC12398026" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Indirect; immune checkpoint glycoproteins involved.", "mechanism": "High UBASH3B expression correlates with poor prognosis and immune cell infiltration.", "protein": "UBASH3B", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "CEACAM1 and HAVCR2 are glycoproteins; glycosylation modulates immune interactions.", "mechanism": "UBASH3B drives immunosuppressive axis (UBASH3B/NR1I2/CEACAM1/HAVCR2), promoting resistance to immunotherapy.", "protein": "UBASH3B", "relationship_type": "causal/immune evasion", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Platelet Activation/Thrombosis", "glycan_involvement": "GPVI is a glycoprotein; glycosylation affects receptor function.", "mechanism": "UBASH3B inhibits GPVI-mediated platelet activation by dephosphorylating Syk.", "protein": "UBASH3B", "relationship_type": "protective", "source_pmcid": "PMC12398026" }, { "confidence": "medium", "disease": "Drug Resistance (Tamoxifen, Erlotinib, Oxaliplatin)", "glycan_involvement": "Indirect; EGFR glycosylation may affect drug binding.", "mechanism": "UBASH3B overexpression confers resistance to tamoxifen (breast cancer) and erlotinib/oxaliplatin (pancreatic cancer).", "protein": "UBASH3B", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Immune Evasion", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation critical for immune checkpoint function.", "mechanism": "UBASH3B stabilizes EGFR, upregulates PD-L1, suppresses MHC expression, and promotes T-cell exhaustion.", "protein": "UBASH3B", "relationship_type": "causal", "source_pmcid": "PMC12398026" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Wnt5a is a secreted glycoprotein; glycosylation required for secretion and activity.", "mechanism": "Wnt5a expression increases with fibrosis grade, promoting progression via noncanonical Wnt signaling.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation enables Wnt5a secretion and receptor binding.", "mechanism": "Macrophage-derived Wnt5a exacerbates inflammation and fibrosis.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Ductular reaction (DR)", "glycan_involvement": "Secreted glycoprotein; glycosylation essential for function.", "mechanism": "Wnt5a promotes HPC differentiation into BECs, driving DR.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Transmembrane glycoprotein; glycosylation affects cell surface localization.", "mechanism": "Fzd2 acts as Wnt5a receptor; upregulated in fibrosis, mediates noncanonical Wnt signaling.", "protein": "Frizzled 2 (Fzd2)", "protein_enriched": { "function": "Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions. Exhibits weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart", "gene_name": "Hcn1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9JKB0" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Liver cirrhosis", "glycan_involvement": "Targeting glycosylated Wnt5a reduces its pathogenic signaling.", "mechanism": "Wnt5a knockdown in M1-BMDMs attenuates cirrhosis and fibrosis.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Ductular reaction (DR)", "glycan_involvement": "Glycosylation required for Fzd2 receptor function.", "mechanism": "Fzd2 knockdown in HPCs inhibits BEC differentiation and DR.", "protein": "Frizzled 2 (Fzd2)", "protein_enriched": { "function": "Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions. Exhibits weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart", "gene_name": "Hcn1", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9JKB0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Ductular reaction (DR)", "glycan_involvement": "Intermediate filament glycoprotein; glycosylation affects stability.", "mechanism": "CK19 marks BECs derived from HPCs during DR.", "protein": "CK19", "relationship_type": "biomarker", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Cell surface glycoprotein; glycosylation modulates cell adhesion.", "mechanism": "EpCam marks activated HPCs in fibrotic liver.", "protein": "EpCam", "relationship_type": "biomarker", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Secreted glycoprotein; glycosylation required for secretion.", "mechanism": "TGF-\u03b21 from macrophages promotes HSC activation and fibrosis.", "protein": "TGF-\u03b21", "protein_enriched": { "function": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active su", "gene_name": "TGFB1", "glycan_count": 17, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G22573RC", "G28622IK", "G02815KT", "G27058EU", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G01485JJ", "G14260UH", "G22768VO", "G25079LO", "G39188ZX", "G56014GC", "G70101JE", "G81315DD", "G49108TO" ], "uniprot_id": "P01137" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation essential for Wnt5a activity.", "mechanism": "Wnt5a/Fzd2 axis drives EMT and cell migration, promoting cancer progression.", "protein": "Wnt5a", "protein_enriched": { "function": "Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-cate", "gene_name": "WNT5A", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G48584BU", "G59626AS", "G62765YT", "G70101JE", "G70841YG", "G80920RR", "G83460ZZ", "G01768RG", "G90659AW", "G29545VG", "G49108TO" ], "uniprot_id": "P41221" }, "relationship_type": "causal", "source_pmcid": "PMC12398029" }, { "confidence": "high", "disease": "Post-hepatectomy liver failure (PHLF)", "glycan_involvement": "N-glycosylation affects albumin stability and serum half-life.", "mechanism": "Low serum albumin reflects poor liver synthetic function and predicts PHLF risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "high", "disease": "PHLF", "glycan_involvement": "Albumin glycosylation modulates bilirubin binding and transport.", "mechanism": "Elevated serum bilirubin post-surgery indicates impaired hepatic clearance.", "protein": "Bilirubin (bound to albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "high", "disease": "PHLF", "glycan_involvement": "ICG binds to glycoproteins for hepatic uptake and excretion.", "mechanism": "ICG clearance rate (ICGR-15) reflects functional hepatocyte mass and predicts PHLF.", "protein": "Indocyanine Green (ICG) Carrier Protein", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "high", "disease": "PHLF", "glycan_involvement": "N-glycosylation critical for coagulation factor secretion and function.", "mechanism": "Elevated INR post-resection indicates impaired synthesis of coagulation glycoproteins.", "protein": "International Normalized Ratio (INR) Factors (e.g., Fibrinogen)", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "medium", "disease": "PHLF", "glycan_involvement": "Glycosylation affects enzyme stability and release.", "mechanism": "Elevated AST reflects hepatocyte injury and predicts PHLF.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "medium", "disease": "PHLF", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Elevated ALT is a marker of hepatocellular damage post-resection.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "medium", "disease": "PHLF", "glycan_involvement": "Surface glycoproteins mediate platelet function and clearance.", "mechanism": "Low platelet count (APRI score) reflects portal hypertension and fibrosis, predicting PHLF.", "protein": "Platelet Glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "high", "disease": "CR-PHLF", "glycan_involvement": "Glycoprotein enzymes in hepatocytes metabolize lactate.", "mechanism": "Elevated postoperative lactate (>1.96 mmol/L) is a sensitive predictor of CR-PHLF due to impaired hepatic clearance.", "protein": "Lactate (metabolized by hepatic glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "medium", "disease": "Hepatitis B infection", "glycan_involvement": "N-glycosylation of HBsAg modulates immune recognition and viral persistence.", "mechanism": "Presence of HBsAg indicates chronic viral infection, a risk factor for PHLF.", "protein": "Hepatitis B Surface Antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC12398035" }, { "confidence": "medium", "disease": "PHLF", "glycan_involvement": "N-glycosylation regulates transporter localization and activity.", "mechanism": "Reduced OATP1B3 function impairs ICG clearance, indicating poor hepatic function.", "protein": "ICG Transporter (OATP1B3)", "protein_enriched": { "function": "ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:176", "gene_name": "ABCB6", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NP58" }, "relationship_type": "causal", "source_pmcid": "PMC12398035" }, { "confidence": "high", "disease": "Metabolic alkalosis", "glycan_involvement": "Indirect; citrate metabolism affects glycoprotein-modulated pathways.", "mechanism": "Excess citrate accumulation during RCA leads to metabolic alkalosis.", "protein": "Citrate (citric acid)", "relationship_type": "causal", "source_pmcid": "PMC12398048" }, { "confidence": "high", "disease": "Hypocalcemia", "glycan_involvement": "Indirect; calcium-binding glycoproteins may be affected.", "mechanism": "Citrate chelates ionized calcium, reducing serum calcium levels.", "protein": "Citrate (citric acid)", "relationship_type": "causal", "source_pmcid": "PMC12398048" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Indirect; anticoagulation affects glycoprotein-mediated clotting.", "mechanism": "Used as anticoagulant in CRRT for AKI patients.", "protein": "Citrate (citric acid)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398048" }, { "confidence": "high", "disease": "Hypocalcemia", "glycan_involvement": "Indirect; restores calcium for glycoprotein function.", "mechanism": "Infused to counteract citrate-induced hypocalcemia.", "protein": "Calcium gluconate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Indirect; affects glycoprotein-mediated coagulation.", "mechanism": "RCA reduces systemic anticoagulation, lowering DIC risk.", "protein": "Citrate (citric acid)", "relationship_type": "protective", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Bleeding diathesis", "glycan_involvement": "Indirect; impacts glycoprotein-dependent clotting.", "mechanism": "RCA minimizes bleeding risk compared to heparin.", "protein": "Citrate (citric acid)", "relationship_type": "protective", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Hepatic dysfunction", "glycan_involvement": "Indirect; liver glycoproteins involved in metabolism.", "mechanism": "Impaired citrate metabolism in liver dysfunction increases overdose risk.", "protein": "Citrate (citric acid)", "relationship_type": "causal", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Heparin-induced thrombocytopenia (HIT)", "glycan_involvement": "Indirect; glycoprotein-mediated platelet activation affected.", "mechanism": "RCA is preferred over heparin to avoid HIT.", "protein": "Citrate (citric acid)", "relationship_type": "protective", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Indirect; metabolic status affects glycoprotein function.", "mechanism": "Citrate levels monitored as indicator of overdose risk in AKI patients.", "protein": "Citrate (citric acid)", "relationship_type": "biomarker", "source_pmcid": "PMC12398048" }, { "confidence": "medium", "disease": "Metabolic alkalosis", "glycan_involvement": "Indirect; calcium is essential for glycoprotein stability.", "mechanism": "Calcium gluconate infusion helps correct metabolic alkalosis secondary to citrate overdose.", "protein": "Calcium gluconate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398048" }, { "confidence": "high", "disease": "Acute decompensated heart failure (ADHF)", "glycan_involvement": "CD41/CD61 is a glycoprotein; glycosylation is essential for its adhesive function.", "mechanism": "Neutrophil-expressed CD41/CD61 promotes neutrophil adhesion to extracellular matrix, contributing to vascular inflammation and thrombosis in ADHF.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "high", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation of CD41/CD61 is required for integrin function and cell-cell interactions.", "mechanism": "Neutrophil CD41/CD61 expression enhances neutrophil-platelet interactions and adhesion, promoting inflammation and thrombus formation in HF.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation supports integrin conformation and ligand binding.", "mechanism": "CD41/CD61 on neutrophils mediates adhesion and interaction with platelets, facilitating thrombus formation.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is necessary for integrin-mediated adhesion.", "mechanism": "Neutrophil-platelet interactions via CD41/CD61 contribute to leukocyte recruitment and plaque development.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "medium", "disease": "Restenosis (angioplasty-related)", "glycan_involvement": "Glycosylation modulates integrin function.", "mechanism": "CD41/CD61-mediated neutrophil recruitment and activation implicated in restenosis after angioplasty.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "medium", "disease": "Pulmonary inflammation", "glycan_involvement": "Glycosylation required for integrin-mediated adhesion.", "mechanism": "CD41/CD61 facilitates neutrophil recruitment and activation in pulmonary inflammatory responses.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "causal", "source_pmcid": "PMC12398050" }, { "confidence": "high", "disease": "Acute decompensated heart failure (ADHF)", "glycan_involvement": "Targeting glycosylated integrin complex may modulate adhesion.", "mechanism": "Blockade of CD41/CD61 (e.g., with eptifibatide) reduces neutrophil adhesion, suggesting therapeutic potential in ADHF.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398050" }, { "confidence": "high", "disease": "Acute decompensated heart failure (ADHF)", "glycan_involvement": "CD18 is a glycoprotein; glycosylation affects integrin function.", "mechanism": "Blocking CD18 reduces neutrophil adhesion, indicating its role in ADHF-associated inflammation.", "protein": "CD18", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398050" }, { "confidence": "medium", "disease": "Heart failure (HF)", "glycan_involvement": "Glycosylation status may influence detection and function.", "mechanism": "Increased intracellular CD41/CD61 in neutrophils from HF patients may serve as a marker of inflammatory activation.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "biomarker", "source_pmcid": "PMC12398050" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation is essential for integrin-ligand interactions.", "mechanism": "Inhibition of CD41/CD61 reduces neutrophil adhesion, suggesting a target for anti-thrombotic therapy.", "protein": "CD41/CD61 complex (GPIIb/IIIa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398050" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "Previously implicated in glycosylation-related gene signatures in other cancers.", "mechanism": "AKAP13 is a risk factor; higher expression correlates with poor prognosis and is involved in T cell mitotic catastrophe.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12398072" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "No direct glycosylation data, but as a nuclear protein may be post-translationally modified.", "mechanism": "SLF2 promotes migration, invasion, and proliferation of ESCC cells; higher expression correlates with poor prognosis.", "protein": "SLF2", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12398072" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "No direct glycosylation data.", "mechanism": "Higher ARAP2 expression correlates with better prognosis; lower in ESCC cell lines.", "protein": "ARAP2", "protein_enriched": { "function": "Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol", "gene_name": "ARAP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8WWN8" }, "relationship_type": "protective biomarker", "source_pmcid": "PMC12398072" }, { "confidence": "medium", "disease": "Uveal Melanoma", "glycan_involvement": "Glycosylation-related gene signature.", "mechanism": "Included in glycosylation-related gene prognostic model for uveal melanoma.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398072" }, { "confidence": "low", "disease": "Prostate Cancer", "glycan_involvement": "No direct glycosylation data.", "mechanism": "Targeted by miR-629-5p, promoting cancer occurrence and metastasis.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "causal", "source_pmcid": "PMC12398072" }, { "confidence": "low", "disease": "Autism Spectrum Disorder", "glycan_involvement": "No direct glycosylation data.", "mechanism": "AKAP13 is associated with autism spectrum disorder.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "associated", "source_pmcid": "PMC12398072" }, { "confidence": "low", "disease": "Long QT Syndrome 8", "glycan_involvement": "No direct glycosylation data.", "mechanism": "AKAP13 is associated with cardiac disease.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "associated", "source_pmcid": "PMC12398072" }, { "confidence": "high", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "No direct glycosylation data.", "mechanism": "SLF2 knockdown impairs ESCC cell migration, invasion, and proliferation; may modulate mitotic catastrophe.", "protein": "SLF2", "relationship_type": "therapeutic target", "source_pmcid": "PMC12398072" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "No direct glycosylation data.", "mechanism": "Molecular docking shows AKAP13 binds Talazoparib, suggesting druggability.", "protein": "AKAP13", "protein_enriched": { "function": "Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by ", "gene_name": "STYXL1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6J8" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12398072" }, { "confidence": "medium", "disease": "Esophageal Squamous Cell Carcinoma (ESCC)", "glycan_involvement": "No direct glycosylation data.", "mechanism": "Molecular docking shows SLF2 binds Talazoparib, suggesting druggability.", "protein": "SLF2", "relationship_type": "therapeutic target", "source_pmcid": "PMC12398072" }, { "confidence": "high", "disease": "Ischemia\u2013reperfusion (I/R) injury", "glycan_involvement": "Glycosylation is required for secretion and stability of IL-1\u03b2.", "mechanism": "IL-1\u03b2 is upregulated during I/R injury, mediating neuroinflammation and tissue damage.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "high", "disease": "Ischemia\u2013reperfusion (I/R) injury", "glycan_involvement": "N-glycosylation modulates IL-6 secretion and receptor binding.", "mechanism": "IL-6 is elevated in I/R injury, promoting inflammatory cascades and neuronal damage.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Ischemia\u2013reperfusion (I/R) injury", "glycan_involvement": "Glycosylation may affect caspase-3 stability and activation.", "mechanism": "Caspase-3 activation mediates neuronal apoptosis after I/R injury.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Ischemia\u2013reperfusion (I/R) injury", "glycan_involvement": "Glycosylation can modulate Bcl-2 localization and function.", "mechanism": "Bcl-2 inhibits apoptosis, and higher Bcl-2/Bax ratio is neuroprotective in I/R injury.", "protein": "Bcl-2", "relationship_type": "protective", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Ischemia\u2013reperfusion (I/R) injury", "glycan_involvement": "Glycosylation may influence Bax stability.", "mechanism": "Bax promotes apoptosis; upregulation leads to neuronal loss in I/R injury.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "causal", "source_pmcid": "PMC12398121" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "IL-1\u03b2 is a key mediator of neuroinflammation following I/R injury.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "N-glycosylation affects IL-6 function.", "mechanism": "IL-6 drives inflammatory response in brain after I/R injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "N-glycosylation modulates IL-6 activity.", "mechanism": "IL-6 is implicated in inflammation and tissue injury post-myocardial infarction.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Renal I/R injury", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "IL-6 mediates inflammatory damage in renal I/R injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "medium", "disease": "Organ transplantation injury", "glycan_involvement": "N-glycosylation modulates IL-6 secretion.", "mechanism": "IL-6 is involved in inflammation and graft injury post-transplantation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398121" }, { "confidence": "high", "disease": "Acute-on-chronic liver failure (ACLF)", "glycan_involvement": "N-glycosylation affects ALB stability and half-life.", "mechanism": "ALB levels decrease in ACLF, reflecting impaired liver synthetic function.", "protein": "Albumin (ALB)", "relationship_type": "biomarker", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "Coagulation dysfunction", "glycan_involvement": "N-glycosylation required for FBG secretion and function.", "mechanism": "FBG is depleted in ACLF, contributing to bleeding risk; replenished via plasma exchange.", "protein": "Fibrinogen (FBG)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "Coagulation dysfunction", "glycan_involvement": "N-glycosylation essential for prothrombin activity.", "mechanism": "Reduced prothrombin activity in ACLF; plasma exchange restores levels.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12398131" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "Fc glycosylation modulates immunoglobulin function.", "mechanism": "Loss during plasma exchange may impair immune defense in ACLF/HIV(+).", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "O-glycosylation regulates CD4 cell surface expression.", "mechanism": "CD4+ T-cell depletion drives immune dysfunction and worsens ACLF prognosis.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398131" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "O-glycosylation affects CD8 stability and function.", "mechanism": "CD8+ T-cell changes correlate with immune status and prognosis in ACLF/HIV(+).", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398131" }, { "confidence": "medium", "disease": "Opportunistic infections", "glycan_involvement": "N-glycosylation required for complement activation.", "mechanism": "Loss during plasma exchange may increase infection risk in ACLF/HIV(+).", "protein": "Complement proteins", "relationship_type": "protective", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "Hepatitis B virus infection", "glycan_involvement": "N-glycosylation modulates antigenicity and immune evasion.", "mechanism": "HBsAg is a marker of HBV infection and liver injury.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates HIV entry and immune cell depletion.", "protein": "HIV gp120", "relationship_type": "causal", "source_pmcid": "PMC12398131" }, { "confidence": "medium", "disease": "Immune dysregulation", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 in ACLF/HIV(+) promotes inflammation and liver injury.", "protein": "Tumor necrosis factor-\u03b1 (TNF-\u03b1)", "relationship_type": "causal", "source_pmcid": "PMC12398131" }, { "confidence": "high", "disease": "B-cell acute lymphoblastic leukemia", "glycan_involvement": "Glycosylation affects CD19 surface expression and CAR recognition.", "mechanism": "CD19 is targeted by CAR-T cells for direct elimination of malignant B cells.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "Multiple myeloma", "glycan_involvement": "Glycosylation modulates BCMA stability and immune recognition.", "mechanism": "BCMA is targeted by CAR-T cells to eliminate myeloma cells.", "protein": "BCMA (TNFRSF17)", "protein_enriched": { "function": "Acts as an acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GSDMD, GAP43, ZDHHC6 or HRAS (PubMed:21152083, PubMed:2882", "gene_name": "LYPLA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95372" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "T cell acute lymphoblastic leukemia", "glycan_involvement": "Glycosylation influences CD7 cell surface expression.", "mechanism": "CD7-targeted CAR-T cells eliminate malignant T cells; CD7 knockout prevents fratricide.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Heparan sulfate glycosylation is essential for GPC3 function and tumor specificity.", "mechanism": "GPC3-targeted CAR-T cells kill GPC3-expressing tumor cells.", "protein": "Glypican-3 (GPC3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "Solid tumors (e.g., breast, lung, pancreatic)", "glycan_involvement": "Aberrant O-glycosylation in cancer exposes MUC1 epitopes for immune targeting.", "mechanism": "MUC1-targeted CAR-T cells attack MUC1-expressing tumor cells.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "medium", "disease": "Solid tumors (e.g., mesothelioma, ovarian, pancreatic)", "glycan_involvement": "Glycosylation affects MSLN immunogenicity and cell surface localization.", "mechanism": "MSLN-targeted CAR-T cells eliminate MSLN-expressing tumor cells.", "protein": "Mesothelin (MSLN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "medium", "disease": "Solid and hematological tumors", "glycan_involvement": "Glycosylation modulates CD47-SIRP\u03b1 interaction.", "mechanism": "CD47 blockade enhances phagocytosis of tumor cells by macrophages.", "protein": "CD47", "protein_enriched": { "function": "Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation o", "gene_name": "CD47", "glycan_count": 86, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G02815KT", "G05049YU", "G07755XJ", "G10486CT", "G10488MI", "G10819WX", "G11314AS", "G18647XP", "G27058EU", "G27915IV", "G28541PG", "G29299MO", "G31852PQ", "G36379GD", "G37399XV", "G39446WN", "G41071NU", "G41247ZX", "G42124LM", "G47644PP", "G47702MW", "G57317CE", "G57776ZS", "G57776ZU", "G60033FS", "G62765YT", "G63041LO", "G65184UU", "G70441OD", "G70619PT", "G72787SB", "G72790NZ", "G79666IR", "G83646BJ", "G85554PZ", "G86182NS", "G87123QX", "G87661QW", "G89827JR", "G90659AW", "G92275SC", "G95177YH", "G95865ZB", "G76535FN", "G22768VO", "G49108TO", "G00912UN", "G01650EU", "G02886BB", "G03574QJ", "G05724UK", "G06110VR", "G10773YW", "G15664MX", "G20210JR", "G23294PN", "G25418HZ", "G27126ED", "G27947YN", "G31986NC", "G33416PL", "G36442WJ", "G39188ZX", "G39619TI", "G40574BA", "G41840AI", "G45395BF", "G48584BU", "G49018RC", "G49906RN", "G51640FO", "G59626AS", "G59924QI", "G64527OM", "G66621EA", "G66760KM", "G72735IY", "G72747WU", "G80223IX", "G80920RR", "G82463GQ", "G84820NF", "G92050GC", "G92062TF", "G92406TI", "G96091TT" ], "uniprot_id": "Q08722" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "Host-versus-graft rejection (HvGR)", "glycan_involvement": "N-glycosylation required for HLA-E stability and surface expression.", "mechanism": "HLA-E expression on UCAR-T cells inhibits NK cell-mediated rejection.", "protein": "HLA-E", "relationship_type": "protective", "source_pmcid": "PMC12398156" }, { "confidence": "high", "disease": "Host-versus-graft rejection (HvGR)", "glycan_involvement": "N-glycosylation critical for HLA-G function.", "mechanism": "HLA-G expression on UCAR-T cells provides immune evasion from NK cells.", "protein": "HLA-G", "protein_enriched": { "function": "Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:19304799, PubMed:23184984, PubMed:29262349). In complex with B2", "gene_name": "HLA-G", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17693" }, "relationship_type": "protective", "source_pmcid": "PMC12398156" }, { "confidence": "medium", "disease": "Solid and hematological tumors", "glycan_involvement": "Glycosylation affects CD1d folding and antigen presentation.", "mechanism": "CD1d presents glycolipid antigens to iNKT cells, enabling anti-tumor immunity.", "protein": "CD1d", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398156" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "N-glycosylation affects albumin stability and function.", "mechanism": "Serum albumin levels reflect liver synthetic function and are measured in MASLD assessment.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation may affect enzyme stability and clearance.", "mechanism": "Elevated AST is indicative of hepatocellular injury in MASLD.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation influences enzyme activity.", "mechanism": "ALT elevation is a marker of liver cell injury in MASLD.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "medium", "disease": "MASLD", "glycan_involvement": "GGT is a membrane glycoprotein; glycosylation affects localization.", "mechanism": "GGT elevation reflects cholestasis and oxidative stress in MASLD.", "protein": "GGT", "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic hyperglycemia, a risk factor for MASLD.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycoprotein components modulate HDL function.", "mechanism": "HDL levels inversely correlate with cardiovascular risk, which is increased in MASLD.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC12398518" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycoprotein components affect LDL receptor binding.", "mechanism": "Elevated LDL promotes atherosclerosis, risk heightened in MASLD.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC12398518" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation regulates platelet adhesion and clearance.", "mechanism": "Platelet count is used in fibrosis scoring; glycoproteins mediate platelet function.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "MASLD", "glycan_involvement": "Glycosylation modulates insulin receptor interaction.", "mechanism": "Insulin resistance drives hepatic steatosis in MASLD.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "MASH", "glycan_involvement": "Glycosylation may affect AST serum half-life.", "mechanism": "AST is a component of the FAST Score for at-risk MASH prediction.", "protein": "AST (in FAST Score)", "relationship_type": "biomarker", "source_pmcid": "PMC12398518" }, { "confidence": "high", "disease": "Arrhythmia", "glycan_involvement": "Glycosylation modulates channel trafficking and function.", "mechanism": "Nifedipine blocks Cav1.2, shortening action potential duration and reducing arrhythmia risk.", "protein": "L-type calcium channel (Cav1.2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398533" }, { "confidence": "high", "disease": "Long QT syndrome", "glycan_involvement": "N-glycosylation required for proper channel folding and surface expression.", "mechanism": "E-4031 blocks hERG, prolonging APD and inducing arrhythmogenic EADs.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "causal", "source_pmcid": "PMC12398533" }, { "confidence": "medium", "disease": "Cardiomyopathy", "glycan_involvement": "Glycosylation affects cell-matrix interactions.", "mechanism": "Fibronectin supports cardiomyocyte adhesion and survival; altered levels linked to cardiac remodeling.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family ", "gene_name": "VTN", "glycan_count": 169, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G29068FM", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03574QJ", "G04854VP", "G05724UK", "G06110VR", "G06247RL", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G11629QQ", "G12313PD", "G14260UH", "G14669DU", "G14889WU", "G15169WU", "G15683CN", "G19379ID", "G22572EH", "G22625SJ", "G23294PN", "G23863VK", "G24954UD", "G25079LO", "G26330YA", "G27058EU", "G27122CE", "G27126ED", "G27947YN", "G28541PG", "G28681TP", "G33609NS", "G33791AF", "G37399XV", "G37868ZX", "G39446WN", "G40834TG", "G41247ZX", "G42358LZ", "G42493LZ", "G44513XM", "G45395BF", "G45504EY", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G48584BU", "G50045TK", "G51640FO", "G52527GH", "G54682XF", "G56610MH", "G57317CE", "G57776ZS", "G57776ZU", "G58232MG", "G58802FE", "G59536GA", "G59626AS", "G60177UT", "G62765YT", "G66163OV", "G69107AL", "G70418MS", "G72291OX", "G72398FA", "G72735IY", "G75983OB", "G78787DI", "G78790NZ", "G80920RR", "G81263BG", "G82463GQ", "G83624CJ", "G84820NF", "G90093AU", "G92050GC", "G94917XT", "G95865ZB", "G98425JK", "G49108TO", "G07799LX", "G08146BT", "G08527WT", "G10846ZT", "G12341GU", "G13661YX", "G14547CB", "G14572XX", "G14972EH", "G16758MX", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G23010ZW", "G24303GI", "G30740WO", "G32788FZ", "G34989PA", "G36131WL", "G37412TK", "G40574BA", "G41522EV", "G43223CG", "G45495MK", "G51941GC", "G54010QB", "G55412XP", "G56518TU", "G57818FI", "G58087IP", "G59324HL", "G70232NH", "G70619PT", "G70888PK", "G72747WU", "G80075MS", "G82830MN", "G84452RH", "G85144OK", "G85269DF", "G86795LJ", "G86880BF", "G88374WZ", "G89827JR", "G90386IR", "G92135MA", "G93860XO", "G94470IW", "G94665LC", "G07810QS", "G11911BT", "G37692EO", "G40926MX", "G42962KI", "G43669FQ", "G44215PV", "G44753VC", "G47644PP", "G58954YZ", "G61256FT", "G63980BQ", "G71146HJ", "G77669RF", "G83229XP", "G86752LQ", "G89045VA", "G90659AW", "G92551JA", "G98129XB", "G99668VU", "G53434XO", "G04273XP", "G06209KS", "G14047PA", "G56749GV", "G66665YI", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P04004" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398533" }, { "confidence": "medium", "disease": "Channelopathies", "glycan_involvement": "N-glycosylation required for membrane localization.", "mechanism": "Na+/K+ ATPase maintains membrane potential; dysfunction leads to abnormal excitability.", "protein": "Na+/K+ ATPase", "protein_enriched": { "function": "This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the e", "gene_name": "ATP1A1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G36379GD", "G49108TO" ], "uniprot_id": "P05023" }, "relationship_type": "causal", "source_pmcid": "PMC12398533" }, { "confidence": "medium", "disease": "Sudden cardiac death", "glycan_involvement": "Glycosylation modulates gating and cell surface expression.", "mechanism": "Nav1.5 mutations disrupt conduction, predisposing to lethal arrhythmias.", "protein": "Voltage-gated sodium channel (Nav1.5)", "relationship_type": "causal", "source_pmcid": "PMC12398533" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "O-glycosylation affects channel assembly.", "mechanism": "Connexin 43 forms gap junctions; altered expression/glycosylation impairs electrical coupling.", "protein": "Connexin 43", "relationship_type": "biomarker", "source_pmcid": "PMC12398533" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "N-glycosylation regulates ligand binding.", "mechanism": "Integrin beta-1 mediates cell-matrix adhesion; supports tissue integrity under stress.", "protein": "Integrin beta-1", "relationship_type": "protective", "source_pmcid": "PMC12398533" }, { "confidence": "low", "disease": "Diastolic dysfunction", "glycan_involvement": "N-glycosylation influences protein stability.", "mechanism": "Troponin T release indicates cardiomyocyte injury; glycosylation may affect stability.", "protein": "Cardiac troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC12398533" }, { "confidence": "low", "disease": "Cardiomyopathy", "glycan_involvement": "Complex glycosylation patterns mediate cell signaling.", "mechanism": "Extracellular matrix glycoproteins regulate cardiomyocyte function and remodeling.", "protein": "Matrigel (laminin, collagen IV, entactin)", "relationship_type": "biomarker", "source_pmcid": "PMC12398533" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MBP is glycosylated; glycosylation affects myelin stability.", "mechanism": "MBP levels reflect myelin integrity and remyelination capacity in MS.", "protein": "MBP", "relationship_type": "biomarker", "source_pmcid": "PMC12398550" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MOG is heavily glycosylated; glycosylation modulates antigenicity.", "mechanism": "MOG is a target of autoimmune response in MS; its levels indicate demyelination.", "protein": "MOG", "relationship_type": "biomarker", "source_pmcid": "PMC12398550" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MAG is a sialic acid-binding glycoprotein; glycosylation critical for function.", "mechanism": "MAG is involved in myelin-axon interactions; reduced in MS lesions.", "protein": "MAG", "relationship_type": "biomarker", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation status influences MOBP stability.", "mechanism": "MOBP expression correlates with mature oligodendrocyte presence and myelination.", "protein": "MOBP", "relationship_type": "biomarker", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "OPALIN is glycosylated; glycosylation affects localization.", "mechanism": "OPALIN marks mature oligodendrocytes; altered in MS.", "protein": "OPALIN", "protein_enriched": { "function": "May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles", "gene_name": "APOL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BQE5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may regulate TOMM20 stability and import activity.", "mechanism": "TOMM20 upregulated by metformin; enhances mitochondrial function in oligodendrocytes.", "protein": "TOMM20", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Potential glycosylation modulates mitochondrial localization.", "mechanism": "CHCHD2 upregulated by metformin; promotes mitochondrial dynamics and oxidative phosphorylation.", "protein": "CHCHD2", "protein_enriched": { "function": "Transcription factor. Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:2330378", "gene_name": "CHCHD2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y6H1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may affect assembly of Complex I.", "mechanism": "NDUFA11 upregulated by metformin; supports mitochondrial respiratory chain function.", "protein": "NDUFA11", "protein_enriched": { "function": "Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro", "gene_name": "NDUFB6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95139" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may regulate activity of Complex IV.", "mechanism": "COX8A upregulated by metformin; enhances mitochondrial electron transport.", "protein": "COX8A", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "COX6A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12074" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398550" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "EIF1 glycosylation may modulate its activity.", "mechanism": "EIF1 upregulated by metformin in MS oligodendrocytes; stimulates translation of mitochondrial mRNAs, supporting energy metabolism.", "protein": "EIF1", "relationship_type": "protective", "source_pmcid": "PMC12398550" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is heavily glycosylated, which modulates immune evasion and receptor binding.", "mechanism": "Spike mediates viral entry via ACE2 binding, driving infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects Spike binding affinity and host susceptibility.", "mechanism": "ACE2 acts as the host receptor for SARS-CoV-2 Spike, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "RBD glycosylation influences antibody accessibility and immune escape.", "mechanism": "RBD is the main target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation sites may modulate mutation effects on antibody binding.", "mechanism": "RBD mutations correlate with immune escape and variant emergence.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of RBD and ACE2 modulates cross-species transmission.", "mechanism": "RBD-ACE2 interaction is essential for viral entry and host range.", "protein": "SARS-CoV-2 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation near RBD may affect antibody binding and escape.", "mechanism": "Neutralizes SARS-CoV-2 by binding Spike RBD; escape mutations (V445H, G446S) reduce efficacy.", "protein": "LY-CoV1404 (bebtelovimab)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence antibody-RBD interaction.", "mechanism": "Neutralizes SARS-CoV-2 by binding Spike RBD; escape mutations (V445H, G446S) abolish activity.", "protein": "REGN10987 (imdevimab)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation at RBD may affect escape mutation impact.", "mechanism": "Broadly neutralizes SARS-CoV-2 variants by binding RBD; escape mutations (G502D, G504D/E) identified.", "protein": "SA55", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Spike RBD mediates ACE2-dependent entry in SARS.", "protein": "SARS-CoV-1 Spike RBD", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12398559" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "E2 glycosylation may affect display and function of RBD fusion.", "mechanism": "Engineered E2-Spike RBD fusion enables safe modeling of SARS-CoV-2 entry and immune escape.", "protein": "Sindbis virus E2 protein (engineered with Spike RBD)", "relationship_type": "therapeutic_target/modeling tool", "source_pmcid": "PMC12398559" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "GSDMD is a glycoprotein; glycosylation may affect stability and membrane localization.", "mechanism": "GSDMD-mediated pyroptosis in osteoblasts increases inflammation, disrupts bone homeostasis, and promotes osteoporosis progression.", "protein": "Gasdermin D (GSDMD)", "protein_enriched": { "function": "Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27281216). This form constitutes the p", "gene_name": "GSDMD", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P57764" }, "relationship_type": "causal", "source_pmcid": "PMC12398577" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "CASP1 is glycosylated; glycosylation may regulate activation.", "mechanism": "CASP1 cleaves GSDMD, triggering pyroptosis and release of pro-inflammatory cytokines, exacerbating bone loss.", "protein": "Caspase-1 (CASP1)", "relationship_type": "causal", "source_pmcid": "PMC12398577" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Possible glycosylation; may affect inflammasome assembly.", "mechanism": "NLRP3 inflammasome activation leads to CASP1 activation and pyroptosis in osteoblasts, promoting inflammation and bone resorption.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12398577" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation affects secretion and stability.", "mechanism": "Elevated IL-1\u03b2 is a marker and mediator of pyroptosis-driven inflammation in osteoporosis.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398577" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "IL-18 is glycosylated; glycosylation affects secretion.", "mechanism": "Elevated IL-18 reflects and drives pyroptosis-induced inflammation, correlating with osteoporosis severity.", "protein": "Interleukin-18 (IL-18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12398577" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "OPN is highly glycosylated; glycosylation modulates cell adhesion and signaling.", "mechanism": "OPN marks osteoblasts; its reduction after pyroptosis indicates impaired bone formation.", "protein": "Osteopontin (OPN)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12398577" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "OCN is glycosylated; glycosylation affects hormone activity.", "mechanism": "OCN expression is reduced in osteoporosis, reflecting impaired osteoblast function.", "protein": "Osteocalcin (OCN)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12398577" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Arg1 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Arg1 marks M2 macrophages; increased Arg1 after treatment indicates anti-inflammatory polarization aiding bone repair.", "protein": "Arginase-1 (Arg1)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC12398577" }, { "confidence": "medium", "disease": "Systemic inflammatory disease", "glycan_involvement": "Possible glycosylation; may regulate inflammasome function.", "mechanism": "NLRP3 inflammasome activation is a driver of systemic inflammation, relevant to osteoporosis as a systemic disease.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12398577" }, { "confidence": "medium", "disease": "Bone defect", "glycan_involvement": "Glycosylation may affect GSDMD membrane targeting.", "mechanism": "GSDMD-mediated pyroptosis impairs osteoblast survival and bone repair in bone defects.", "protein": "Gasdermin D (GSDMD)", "protein_enriched": { "function": "Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27281216). This form constitutes the p", "gene_name": "GSDMD", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P57764" }, "relationship_type": "causal", "source_pmcid": "PMC12398577" }, { "confidence": "high", "disease": "Lipid disorders", "glycan_involvement": "N-glycosylation affects stability and localization.", "mechanism": "Catalyzes rate-limiting step in cholesterol biosynthesis; targeted by statins.", "protein": "HMG-CoA reductase (HMGCR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398585" }, { "confidence": "high", "disease": "Tumors (Cancer)", "glycan_involvement": "N-glycosylation modulates ligand binding and receptor activation.", "mechanism": "EGFR signaling drives cell proliferation in cancer.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398585" }, { "confidence": "high", "disease": "Diabetes", "glycan_involvement": "Glycation (non-enzymatic glycan modification) alters function.", "mechanism": "Albumin glycation is a marker for diabetes progression.", "protein": "ALB (Albumin)", "relationship_type": "biomarker", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Tumors (Cancer)", "glycan_involvement": "Glycosylation may affect chaperone activity and client interaction.", "mechanism": "Chaperone stabilizes oncogenic proteins.", "protein": "HSP90AA1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "IGF1 signaling modulates insulin sensitivity.", "protein": "IGF1", "relationship_type": "causal", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Indirect; upstream glycoproteins modulate AKT1 activation.", "mechanism": "AKT1 mediates insulin signaling; dysregulation leads to resistance.", "protein": "AKT1", "relationship_type": "causal", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may regulate activation and localization.", "mechanism": "CASP3 mediates apoptosis in vascular cells.", "protein": "CASP3", "relationship_type": "causal", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation affects membrane localization and signaling.", "mechanism": "SRC kinase promotes tumor progression.", "protein": "SRC", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors", "gene_name": "SRC", "glycan_count": 9, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10486CT", "G27947YN", "G57317CE", "G57776ZU", "G59324HL", "G80920RR", "G82443XX", "G90659AW", "G49108TO" ], "uniprot_id": "P12931" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Indirect; glycosylation of co-regulators modulates activity.", "mechanism": "PPARG regulates glucose and lipid metabolism.", "protein": "PPARG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12398585" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "Glycosylation of upstream receptors affects MAPK1 activation.", "mechanism": "MAPK1 involved in neuronal signaling and survival.", "protein": "MAPK1", "relationship_type": "causal", "source_pmcid": "PMC12398585" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation affects insulin receptor binding and clearance.", "mechanism": "Insulin levels and resistance are central to T2DM pathogenesis and metabolic dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates albumin stability and function.", "mechanism": "Serum albumin reflects nutritional status, which influences bone health.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Adipokines secreted by adipose tissue modulate bone metabolism and inflammation.", "protein": "Adipokines (e.g., leptin)", "relationship_type": "causal", "source_pmcid": "PMC12399443" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation affects cytokine stability and signaling.", "mechanism": "Pro-inflammatory cytokines promote osteoclast activation and bone resorption.", "protein": "Inflammatory cytokines (TNF-\u03b1, IL-6)", "relationship_type": "causal", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation modulates enzyme activity and localization.", "mechanism": "Aromatase in adipose tissue converts androgens to estrogens, supporting bone mass in postmenopausal women.", "protein": "Aromatase (CYP19A1)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (P", "gene_name": "CYP19A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11511" }, "relationship_type": "protective", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Glycosylation influences peptide stability.", "mechanism": "C-peptide levels reflect endogenous insulin secretion and \u03b2-cell function.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Bone Mineral Density Reduction", "glycan_involvement": "Glycosylation affects secretion and bone matrix binding.", "mechanism": "Osteocalcin is a marker of bone formation; reduced levels indicate impaired bone metabolism.", "protein": "Osteocalcin", "protein_enriched": { "function": "Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impai", "gene_name": "BGLAP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02818" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates hormone stability and receptor interaction.", "mechanism": "Elevated PTH increases bone resorption, contributing to osteoporosis.", "protein": "Parathyroid hormone (PTH)", "relationship_type": "causal", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "N-glycosylation affects SHBG half-life and hormone binding.", "mechanism": "SHBG regulates bioavailability of sex hormones, impacting bone health.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "medium", "disease": "Sarcopenic Obesity", "glycan_involvement": "Glycosylation (glycated hemoglobin) is a marker of chronic hyperglycemia.", "mechanism": "Lower hemoglobin may reflect poor nutritional status and increased risk of sarcopenic obesity.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12399443" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "AFP is a glycoprotein; altered glycosylation increases diagnostic specificity.", "mechanism": "Elevated serum AFP is associated with HCC presence and progression.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation status may affect stability and function.", "mechanism": "Serum albumin levels reflect liver function and prognosis in HCC.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "PD-L1 glycosylation modulates immune evasion and antibody binding.", "mechanism": "PD-L1 expression correlates with poor response to immunotherapy and low LMR.", "protein": "Programmed death-ligand 1 (PD-L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Defective carboxylation/glycosylation leads to PIVKA-II accumulation.", "mechanism": "Elevated PIVKA-II indicates abnormal prothrombin glycosylation in HCC.", "protein": "PIVKA-II (Des-gamma-carboxy prothrombin)", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Platelet surface glycoproteins mediate adhesion and tumor cell interactions.", "mechanism": "Platelet-to-lymphocyte ratio (PLR) predicts metastatic potential and prognosis.", "protein": "Platelet glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Neutrophil glycoproteins influence migration and inflammatory signaling.", "mechanism": "Neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and poor prognosis.", "protein": "Neutrophil glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Lymphocyte glycoproteins modulate immune surveillance and tumor recognition.", "mechanism": "Low lymphocyte counts (NLR, LMR) are associated with poor survival.", "protein": "Lymphocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Monocyte glycoproteins affect migration and tumor microenvironment modulation.", "mechanism": "High monocyte counts (low LMR) correlate with poor prognosis and immunosuppression.", "protein": "Monocyte glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "low", "disease": "Gastric cancer", "glycan_involvement": "AFP glycosylation patterns may differ in non-hepatic tumors.", "mechanism": "AFP can be elevated in some gastric cancers, indicating aggressive disease.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC12399463" }, { "confidence": "medium", "disease": "Lung cancer", "glycan_involvement": "PD-L1 glycosylation affects antibody recognition and immune escape.", "mechanism": "PD-L1 expression predicts response to checkpoint inhibitors.", "protein": "Programmed death-ligand 1 (PD-L1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12399463" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "None; TOP2A is not glycosylated.", "mechanism": "TOP2A is upregulated in HCC tissues and correlates with poor prognosis.", "protein": "TOP2A", "relationship_type": "biomarker", "source_pmcid": "PMC12399748" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "None; TOP2A is not glycosylated.", "mechanism": "Knockdown of TOP2A inhibits proliferation, migration, invasion, and induces apoptosis in HCC cells.", "protein": "TOP2A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "Immune evasion in HCC", "glycan_involvement": "Indirect; mediated through glycoproteins SPP1 and CD44.", "mechanism": "TOP2A promotes immune escape by driving T cell exhaustion via the SPP1-CD44 axis.", "protein": "TOP2A", "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "CD44 is a heavily glycosylated protein; glycosylation modulates ligand binding and cell adhesion.", "mechanism": "CD44 overexpression promotes tumor progression, invasion, and immune suppression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "SPP1 is glycosylated; glycosylation affects its interaction with CD44 and immune cells.", "mechanism": "SPP1 promotes EMT, drug resistance, and macrophage polarization, accelerating HCC progression.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "T cell exhaustion", "glycan_involvement": "Glycosylation of SPP1 and CD44 is essential for their interaction and signaling.", "mechanism": "SPP1-CD44 axis promotes T cell exhaustion, reducing anti-tumor immunity.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "T cell exhaustion", "glycan_involvement": "CD44 glycosylation modulates its receptor function and immune signaling.", "mechanism": "CD44 engagement by SPP1 leads to T cell exhaustion and immune suppression in HCC.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "Immune evasion in HCC", "glycan_involvement": "Glycosylation of CD44 is critical for its immunomodulatory functions.", "mechanism": "CD44 mediates immune escape by promoting T cell exhaustion and suppressing sustained T cell proliferation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "Immune evasion in HCC", "glycan_involvement": "Glycosylation of SPP1 enhances its binding to CD44 and immune cells.", "mechanism": "SPP1 triggers immunosuppressive signaling via CD44, facilitating immune evasion.", "protein": "SPP1 (Osteopontin)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "medium", "disease": "Chemotherapy resistance in HCC", "glycan_involvement": "CD44 glycosylation affects drug resistance mechanisms.", "mechanism": "SPP1/CD44 axis confers drug resistance by activating CD44 receptor signaling.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12399748" }, { "confidence": "high", "disease": "Malignant Pericardial Effusion", "glycan_involvement": "EpCAM is a heavily glycosylated cell surface glycoprotein; glycosylation affects cell adhesion and immune recognition.", "mechanism": "Ber-EP4 positivity in pericardial fluid cytology identifies malignant epithelial cells.", "protein": "Ber-EP4 antigen (EpCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12399826" }, { "confidence": "high", "disease": "Squamous Cell Carcinoma of the Lung", "glycan_involvement": "Glycosylation modulates EpCAM's cell-cell interaction and tumorigenicity.", "mechanism": "Ber-EP4 is used to distinguish carcinoma cells in cytology, supporting SCC diagnosis.", "protein": "Ber-EP4 antigen (EpCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC12399826" }, { "confidence": "medium", "disease": "Malignant Pericardial Effusion", "glycan_involvement": "Calretinin is glycosylated, which may affect its stability and detection.", "mechanism": "Calretinin positivity marks mesothelial cells, helping differentiate malignant from reactive effusions.", "protein": "Calretinin", "protein_enriched": { "function": "Calcium-binding protein involved in calcium homeostasis and signal transduction. It plays a critical role in buffering intracellular calcium levels and modulating calcium-dependent signaling pathways ", "gene_name": "CALB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22676" }, "relationship_type": "biomarker", "source_pmcid": "PMC12399826" }, { "confidence": "high", "disease": "Squamous Cell Carcinoma of the Lung", "glycan_involvement": "CK7 is O-glycosylated, influencing filament assembly and antigenicity.", "mechanism": "CK7 positivity in immunohistochemistry supports diagnosis of SCC and NSCLC.", "protein": "Cytokeratin 7", "relationship_type": "biomarker", "source_pmcid": "PMC12399826" }, { "confidence": "medium", "disease": "Squamous Cell Carcinoma of the Lung", "glycan_involvement": "TTF-1 is glycosylated, which may affect nuclear localization and detection.", "mechanism": "TTF-1 negativity helps exclude adenocarcinoma, supporting SCC diagnosis.", "protein": "Thyroid Transcription Factor-1 (TTF-1)", "relationship_type": "biomarker", "source_pmcid": "PMC12399826" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "CD44 glycosylation modulates ligand binding and cell adhesion.", "mechanism": "CD44 overexpression promotes cancer stemness, metastasis, and chemoresistance via interaction with hyaluronic acid and upregulation of EMT and MDR1.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12400058" }, { "confidence": "high", "disease": "Metastatic cervical cancer", "glycan_involvement": "Glycosylation of CD44 affects HA binding and metastatic potential.", "mechanism": "CD44-HA binding drives EMT, cell invasion, and metastatic signaling.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "high", "disease": "Chemoresistant cervical cancer", "glycan_involvement": "Glycosylation influences CD44 stability and drug resistance signaling.", "mechanism": "CD44 upregulates MDR1 and EMT pathways, leading to carboplatin resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Metastatic cervical cancer", "glycan_involvement": "Alternative splicing and glycosylation of CD44v6 enhance metastatic signaling.", "mechanism": "CD44v6 variant promotes cytoskeletal changes, proliferation, and EMT via MAPK/Ras and VEGF pathways.", "protein": "CD44v6", "protein_enriched": { "function": "Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:197", "gene_name": "CD44", "glycan_count": 81, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G57321FI", "G53434XO", "G43417UB", "G48414YA", "G10486CT", "G00912UN", "G02030ZB", "G05962QB", "G06247RL", "G06330RB", "G06356OH", "G08918WF", "G11629QQ", "G13694XX", "G15169WU", "G20312EM", "G22310AV", "G23010ZW", "G24517ZG", "G25418HZ", "G25451PN", "G27058EU", "G27947YN", "G33791AF", "G37818NZ", "G37881RL", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G43223CG", "G44215PV", "G45395BF", "G46524LG", "G47012YE", "G47518TP", "G51413EV", "G52527GH", "G53075ES", "G55412XP", "G56784JY", "G57776ZS", "G57888GL", "G59324HL", "G59536GA", "G59626AS", "G60834IK", "G62461SM", "G64394MX", "G65019XG", "G66163OV", "G66760KM", "G69521XL", "G70232NH", "G70888PK", "G75983OB", "G76417NN", "G77547TA", "G77582RK", "G79666IR", "G80075MS", "G80223IX", "G81637OR", "G82443XX", "G82830MN", "G83646BJ", "G84452RH", "G86880BF", "G87123QX", "G90093AU", "G90382BL", "G91344EV", "G91473PK", "G94831VI", "G95133RI", "G96577RX", "G98611JV", "G56770VP", "G80920RR", "G71784JC", "G49108TO" ], "uniprot_id": "P16070" }, "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Chemoresistant cervical cancer", "glycan_involvement": "MDR1 glycosylation affects membrane localization and function.", "mechanism": "CD44-positive cells upregulate MDR1, increasing drug efflux and resistance.", "protein": "MDR1 (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation stabilizes E-cadherin at cell junctions.", "mechanism": "Resveratrol promotes E-cadherin transcription, inhibiting EMT and metastasis.", "protein": "E-cadherin (CDH1)", "relationship_type": "protective", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Metastatic cervical cancer", "glycan_involvement": "Glycosylation modulates N-cadherin-mediated cell migration.", "mechanism": "Upregulation of N-cadherin is associated with EMT and metastasis; resveratrol reduces its expression.", "protein": "N-cadherin (CDH2)", "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "low", "disease": "Metastatic cervical cancer", "glycan_involvement": "Glycosylation may affect vimentin filament assembly.", "mechanism": "Vimentin upregulation marks EMT and metastasis; resveratrol inhibits its expression.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "causal", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation regulates CD44-mediated drug resistance.", "mechanism": "CD44-positive ovarian cancer cells show increased carboplatin resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12400058" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation affects CD44 signaling and drug response.", "mechanism": "Resveratrol downregulates CD44, sensitizing cells to carboplatin and reducing glycolysis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12400058" }, { "confidence": "high", "disease": "CAP", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Stimulates granulocyte proliferation; levels decrease during ICU stay, associated with disease progression.", "protein": "CSF3 (G-CSF)", "relationship_type": "biomarker", "source_pmcid": "PMC12400547" }, { "confidence": "high", "disease": "CAP", "glycan_involvement": "N-glycosylation affects receptor binding and bioactivity.", "mechanism": "Upregulated in acute infection; associated with mortality, mechanical ventilation, and renal injury; decreases over time in survivors.", "protein": "IL6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12400547" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates immune signaling.", "mechanism": "Central to cytokine storm and disease severity; IL-6 inhibitors reduce adverse outcomes.", "protein": "IL6", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "Interstitial lung disease", "glycan_involvement": "N-glycosylation required for receptor interaction.", "mechanism": "Promotes lung fibroblast proliferation and collagen deposition; overexpression linked to fibrosis.", "protein": "PDGFB", "relationship_type": "causal", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "Long COVID", "glycan_involvement": "N-glycosylation influences angiogenic activity.", "mechanism": "Elevated plasma levels in long COVID; involved in vascular homeostasis.", "protein": "ANGPT1", "relationship_type": "biomarker", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "CAP", "glycan_involvement": "N-glycosylation affects vascular function.", "mechanism": "Decreased plasma levels in CAP; imbalance with ANGPT2 may correlate with mortality.", "protein": "ANGPT1", "relationship_type": "biomarker", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "CAP", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Limits excessive inflammation; essential for effective immune response during Streptococcus pneumoniae infection.", "protein": "IL10RA", "protein_enriched": { "function": "Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a", "gene_name": "IL10RA", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q13651" }, "relationship_type": "protective", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "O-glycosylation modulates chemokine activity.", "mechanism": "Autoantibodies to CCL13 in convalescent COVID-19 associated with reduced risk of long COVID.", "protein": "CCL13", "protein_enriched": { "function": "Chemotactic for resting T-lymphocytes, and eosinophils (PubMed:9104803, PubMed:9365122). Has lower chemotactic activity for neutrophils but none for monocytes and activated lymphocytes (PubMed:9104803", "gene_name": "CCL24", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G22310AV" ], "uniprot_id": "O00175" }, "relationship_type": "protective", "source_pmcid": "PMC12400547" }, { "confidence": "medium", "disease": "CAP", "glycan_involvement": "N-glycosylation required for receptor stability.", "mechanism": "Positively associated with mortality, AKI, and AST levels in CAP patients.", "protein": "IL5RA", "protein_enriched": { "function": "Cell surface receptor that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:9378992). Acts by forming a heterodimeric receptor with CSF2RB subunit and su", "gene_name": "IL5RA", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q01344" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400547" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects cell surface expression.", "mechanism": "Expressed on NK cells; associated with AST levels in COVID-19.", "protein": "SLAMF7", "protein_enriched": { "function": "Probable immunoglobulin-like cell surface receptor. On binding with CD47, mediates cell-cell adhesion. Engagement on T-cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-", "gene_name": "SIRPG", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9P1W8" }, "relationship_type": "biomarker", "source_pmcid": "PMC12400547" }, { "confidence": "high", "disease": "Autoimmune hepatitis", "glycan_involvement": "OX40 is a glycoprotein; glycosylation is required for proper cell surface expression and ligand binding.", "mechanism": "OX40 promotes DNT cell survival and immunoregulatory function, protecting against autoimmune hepatitis.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "medium", "disease": "Graft-versus-host disease", "glycan_involvement": "Glycosylation modulates OX40 signaling and stability.", "mechanism": "OX40 supports DNT cell-mediated immunoregulation, reducing GVHD severity.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "medium", "disease": "Transplant rejection", "glycan_involvement": "Glycosylation affects OX40 receptor-ligand interactions.", "mechanism": "OX40 enhances DNT cell function, contributing to immune tolerance in transplantation.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "low", "disease": "Asthma", "glycan_involvement": "Glycosylation is necessary for OX40 surface expression.", "mechanism": "OX40-expressing DNT cells regulate immune responses in asthma.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "low", "disease": "Psoriasis", "glycan_involvement": "Glycosylation impacts OX40 function.", "mechanism": "OX40+ DNT cells modulate immune activity in psoriasis.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "low", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation required for OX40 signaling.", "mechanism": "OX40+ DNT cells suppress autoreactive T cells in T1D.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "medium", "disease": "Atopic dermatitis", "glycan_involvement": "Glycosylation modulates OX40\u2013OX40L interactions.", "mechanism": "OX40\u2013OX40L pathway dysregulation is implicated in atopic dermatitis; targeting OX40 may be therapeutic.", "protein": "OX40 (TNFRSF4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401205" }, { "confidence": "high", "disease": "Autoimmune hepatitis", "glycan_involvement": "GZMB is glycosylated for secretion and stability.", "mechanism": "GZMB expression in DNT cells mediates cytotoxicity against pathogenic T cells, reducing liver injury.", "protein": "Granzyme B (GZMB)", "relationship_type": "protective", "source_pmcid": "PMC12401205" }, { "confidence": "high", "disease": "Autoimmune hepatitis", "glycan_involvement": "Glycosylation required for PRF1 secretion.", "mechanism": "PRF1 in DNT cells enables cytotoxic elimination of autoreactive T cells.", "protein": "Perforin (PRF1)", "relationship_type": "protective", "source_pmcid": "PMC12401205" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "NKG2D glycosylation is essential for ligand recognition.", "mechanism": "NKG2D expression in DNT cells enhances their immunoregulatory cytotoxicity.", "protein": "NKG2D (KLRK1)", "protein_enriched": { "function": "Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. ", "gene_name": "Smc1a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z1M9" }, "relationship_type": "protective", "source_pmcid": "PMC12401205" }, { "confidence": "high", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "TROP-2 is a glycoprotein; glycosylation may affect its cell surface localization and antibody recognition.", "mechanism": "TROP-2 is selectively overexpressed in pRCC, enabling targeted delivery of cytotoxic agents via antibody-drug conjugates (ADC) such as Sacituzumab govitecan.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Glycosylation may influence detection by immunohistochemistry and ELISA.", "mechanism": "Elevated TROP-2 mRNA and protein levels in pRCC distinguish it from other RCC subtypes and benign tumors.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Glycosylation may modulate ADC binding and internalization.", "mechanism": "Functional relevance demonstrated by cytotoxicity of Sacituzumab govitecan in TROP-2-positive RCC cell lines.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401752" }, { "confidence": "medium", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Soluble glycosylated TROP-2 detected in serum.", "mechanism": "Serum TROP-2 levels correlate with tissue expression, supporting its use as a companion diagnostic.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Clear Cell Renal Cell Carcinoma (ccRCC)", "glycan_involvement": "Glycosylation status may affect low detectability.", "mechanism": "TROP-2 expression is absent or weak in ccRCC, distinguishing it from pRCC.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Chromophobe Renal Cell Carcinoma (chRCC)", "glycan_involvement": "Glycosylation status may affect low detectability.", "mechanism": "TROP-2 expression is absent or weak in chRCC, distinguishing it from pRCC.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Benign Renal Tumors (Oncocytoma, Angiomyolipoma)", "glycan_involvement": "Glycosylation status may affect detectability.", "mechanism": "TROP-2 expression is low or absent in benign renal tumors, supporting its specificity for malignant disease.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "medium", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Glycosylation may influence cell surface abundance.", "mechanism": "TROP-2 expression is associated with local tumor burden in pRCC.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "medium", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Glycosylation may facilitate internalization and trafficking.", "mechanism": "SG treatment leads to internalization and degradation of TROP-2 in TROP-2-positive RCC cells.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12401752" }, { "confidence": "medium", "disease": "Papillary Renal Cell Carcinoma (pRCC)", "glycan_involvement": "Glycosylation may affect antibody binding and patient selection.", "mechanism": "TROP-2 expression enables patient stratification for ADC therapy.", "protein": "TROP-2", "protein_enriched": { "function": "May function as a growth factor receptor", "gene_name": "TACSTD2", "glycan_count": 34, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G23294PN", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G57776ZU", "G62765YT", "G62894KT", "G64527OM", "G70232NH", "G80920RR", "G49108TO", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G43223CG", "G61256FT", "G68490OW", "G79666IR", "G83229XP", "G83460ZZ", "G87661QW", "G04657PL", "G27058EU", "G45395BF", "G84452RH", "G57321FI" ], "uniprot_id": "P09758" }, "relationship_type": "biomarker", "source_pmcid": "PMC12401752" }, { "confidence": "high", "disease": "Heatstroke", "glycan_involvement": "N-glycosylation modulates anti-protease and anti-inflammatory activity.", "mechanism": "Downregulation reflects resolution of inflammation during recovery.", "protein": "Alpha-1 antitrypsin (A1AT)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "N-glycosylation affects stability and renal filtration.", "mechanism": "Downregulation during recovery; upregulation in early AKI reflects oxidative stress and tissue protection.", "protein": "Alpha-1 microglobulin/bikunin precursor (AMBP/A1M)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Heatstroke", "glycan_involvement": "Glycosylation of both A1M and IgA mediates complex formation and immune modulation.", "mechanism": "Complex formation may exert anti-inflammatory effects during heatstroke.", "protein": "Alpha-1 microglobulin\u2013IgA complex", "relationship_type": "protective", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Renal stress (Heatstroke-induced)", "glycan_involvement": "N-glycosylation influences lipid transport and anti-inflammatory properties.", "mechanism": "Upregulation indicates renal stress and lipid metabolism changes during recovery.", "protein": "Apolipoprotein A-IV (APOA4)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Renal stress (Heatstroke-induced)", "glycan_involvement": "N-glycosylation critical for chaperone function and tissue protection.", "mechanism": "Upregulation reflects renal stress and recovery; involved in cell protection and apoptosis regulation.", "protein": "Clusterin (Apolipoprotein J)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Heatstroke", "glycan_involvement": "N-glycosylation required for complement activation and stability.", "mechanism": "Upregulation during recovery; initiates complement cascade, previously unreported in heat stress.", "protein": "Complement component 2 (C2)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation patterns affect immunomodulatory activity.", "mechanism": "Modulates immune response and inflammation in chronic/autoimmune conditions.", "protein": "Alpha-1 antitrypsin (A1AT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation impacts antioxidant function.", "mechanism": "Reflects oxidative stress and tissue damage in sepsis and heatstroke.", "protein": "Alpha-1 microglobulin/bikunin precursor (AMBP/A1M)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "low", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation required for interaction with coagulation factors.", "mechanism": "Involved in coagulation and cell protection during systemic inflammation.", "protein": "Clusterin (Apolipoprotein J)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "medium", "disease": "Multiorgan dysfunction (Heatstroke)", "glycan_involvement": "N-glycosylation essential for complement cascade function.", "mechanism": "Reflects complement activation and systemic inflammation in organ dysfunction.", "protein": "Complement component 2 (C2)", "relationship_type": "biomarker", "source_pmcid": "PMC12402120" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Upregulated in GA; mediates matrix degradation and inflammatory cell recruitment.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation affects stability and localization.", "mechanism": "Induced by MSU crystals; drives PGE2 production and inflammation.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Upregulated in GA; catalyzes ROS production, contributing to tissue damage.", "protein": "MPO", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "N-glycosylation essential for receptor binding.", "mechanism": "Elevated in GA; promotes angiogenesis in inflamed synovium.", "protein": "VEGF", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation influences chemokine gradient formation.", "mechanism": "Increased in GA; recruits monocytes and neutrophils to joints.", "protein": "MCP-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "medium", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation affects secretion and proteolytic activity.", "mechanism": "Upregulated in GA; mediates neutrophil infiltration and tissue breakdown.", "protein": "Elastase", "protein_enriched": { "function": "Cleaves host elastin, collagen, IgG, and several complement components as well as endogenous pro-aminopeptidase (PubMed:11533066). Autocatalyses processing of its pro-peptide (PubMed:1744034, PubMed:9", "gene_name": "lasB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14756" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Synovitis", "glycan_involvement": "Glycosylation required for extracellular activity.", "mechanism": "Overexpressed in synovial fluid; drives inflammation and joint destruction.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Glycosylation modulates enzyme function.", "mechanism": "Induced in OA; mediates pain and inflammation via prostaglandin synthesis.", "protein": "COX-2", "protein_enriched": { "function": "Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a par", "gene_name": "Ptgs2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P35355" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402284" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "N-glycosylation required for activity.", "mechanism": "Promotes pathological angiogenesis in RA synovium.", "protein": "VEGF", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects chemokine function.", "mechanism": "Elevated in RA; drives leukocyte recruitment and inflammation.", "protein": "MCP-1", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402284" }, { "confidence": "high", "disease": "Long QT Syndrome (LQTS)", "glycan_involvement": "Glycosylation is essential for hERG channel maturation and membrane trafficking.", "mechanism": "Blockade or impaired trafficking of hERG channels prolongs cardiac repolarization, leading to QTc interval prolongation.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "causal", "source_pmcid": "PMC12402316" }, { "confidence": "high", "disease": "Torsades de Pointes (TdP)", "glycan_involvement": "Glycosylation defects can impair hERG function, contributing to arrhythmia.", "mechanism": "Prolonged QTc due to hERG dysfunction increases risk of TdP.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "causal", "source_pmcid": "PMC12402316" }, { "confidence": "medium", "disease": "Sudden Cardiac Death", "glycan_involvement": "Glycosylation status affects hERG stability and function.", "mechanism": "QT prolongation from hERG blockade predisposes to fatal arrhythmias.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "causal", "source_pmcid": "PMC12402316" }, { "confidence": "medium", "disease": "Cardiac Arrest", "glycan_involvement": "Glycosylation required for proper hERG channel surface expression.", "mechanism": "Drug-induced QT prolongation via hERG blockade can trigger cardiac arrest.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "causal", "source_pmcid": "PMC12402316" }, { "confidence": "medium", "disease": "Long QT Syndrome (LQTS)", "glycan_involvement": "Altered glycosylation may affect biomarker reliability.", "mechanism": "QTc interval is a clinical biomarker for hERG channel dysfunction.", "protein": "hERG potassium channel (KCNH2)", "relationship_type": "biomarker", "source_pmcid": "PMC12402316" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "GnRHR glycosylation affects receptor stability and ligand binding.", "mechanism": "Triptorelin activates GnRHR, suppressing LH/FSH and testosterone, slowing tumor growth.", "protein": "GnRHR", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402341" }, { "confidence": "high", "disease": "Endometriosis", "glycan_involvement": "FSH glycosylation modulates bioactivity and half-life.", "mechanism": "Triptorelin suppresses FSH, reducing estrogen and endometrial proliferation.", "protein": "FSH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402341" }, { "confidence": "high", "disease": "Central precocious puberty (CPP)", "glycan_involvement": "LH glycosylation affects receptor interaction and clearance.", "mechanism": "Triptorelin suppresses LH surge, halting premature sexual development.", "protein": "LH", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402341" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "PSA glycosylation influences detection and diagnostic accuracy.", "mechanism": "PSA levels monitored to assess prostate cancer progression and triptorelin efficacy.", "protein": "PSA", "relationship_type": "biomarker", "source_pmcid": "PMC12402341" }, { "confidence": "low", "disease": "Alzheimer's dementia", "glycan_involvement": "APP glycosylation affects amyloidogenic processing.", "mechanism": "Triptorelin-associated signal for Alzheimer's dementia; possible neuroendocrine modulation of APP processing.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "hypothesized causal", "source_pmcid": "PMC12402341" }, { "confidence": "medium", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation critical for bone matrix protein function.", "mechanism": "Triptorelin-induced hypogonadism reduces bone matrix glycoprotein synthesis, increasing osteoporosis risk.", "protein": "Bone matrix glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12402341" }, { "confidence": "medium", "disease": "Ovarian hyperstimulation syndrome", "glycan_involvement": "FSH glycosylation affects ovarian response.", "mechanism": "Triptorelin modulates FSH, occasionally leading to ovarian hyperstimulation.", "protein": "FSH", "relationship_type": "causal", "source_pmcid": "PMC12402341" }, { "confidence": "medium", "disease": "Testicular atrophy", "glycan_involvement": "LH glycosylation modulates activity.", "mechanism": "Triptorelin suppresses LH, leading to reduced testosterone and testicular atrophy.", "protein": "LH", "relationship_type": "causal", "source_pmcid": "PMC12402341" }, { "confidence": "low", "disease": "Pituitary apoplexy", "glycan_involvement": "Glycosylation affects hormone secretion and stability.", "mechanism": "Triptorelin may trigger pituitary apoplexy via acute hormonal shifts.", "protein": "Pituitary hormones", "relationship_type": "causal", "source_pmcid": "PMC12402341" }, { "confidence": "medium", "disease": "Growth retardation", "glycan_involvement": "GH glycosylation influences growth-promoting activity.", "mechanism": "Triptorelin suppresses GH axis, leading to transient growth retardation in children.", "protein": "GH", "relationship_type": "causal", "source_pmcid": "PMC12402341" }, { "confidence": "high", "disease": "Dilated cardiomyopathy", "glycan_involvement": "TRPV2 is glycosylated, affecting trafficking and membrane localization.", "mechanism": "TRPV2 deficiency impairs cardiac function and structure.", "protein": "TRPV2", "relationship_type": "causal", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy", "glycan_involvement": "Glycosylation may regulate TRPV2 function in muscle cells.", "mechanism": "TRPV2 implicated in cardiomyopathy associated with DMD.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation influences TRPV2 channel activity.", "mechanism": "TRPV2 modulates calcium influx during cardiac injury.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Ischemia/reperfusion injury", "glycan_involvement": "Glycosylation affects TRPV2 membrane translocation.", "mechanism": "TRPV2 activation contributes to injury; inhibition is protective.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Diabetic cardiomyopathy", "glycan_involvement": "Glycosylation modulates TRPV2 function under hyperglycemic conditions.", "mechanism": "TRPV2 regulates calcium signaling in diabetic heart tissue.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may affect TRPV2-mediated cell adhesion.", "mechanism": "TRPV2 promotes tumor cell migration and adhesion.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation status may regulate TRPV2 surface expression.", "mechanism": "TRPV2 enhances invasiveness and metastasis.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Hepatocarcinoma", "glycan_involvement": "Glycosylation may influence TRPV2 function in hepatic cells.", "mechanism": "TRPV2 mediates cancer progression via cell migration.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation potentially modulates TRPV2 activity.", "mechanism": "TRPV2 involved in tumor invasiveness.", "protein": "TRPV2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402448" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects troponin I stability and detection.", "mechanism": "Troponin I elevation indicates acute myocardial injury.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12402448" }, { "confidence": "high", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Glycosylation affects stability and detection sensitivity.", "mechanism": "Elevated serum cTn-I indicates myocardial injury after DOX treatment.", "protein": "Cardiac Troponin I (cTn-I)", "relationship_type": "biomarker", "source_pmcid": "PMC12402467" }, { "confidence": "high", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "DOX increases PINK1 expression, activating mitophagy and contributing to mitochondrial damage.", "protein": "PTEN-Induced Putative Kinase 1 (PINK1)", "relationship_type": "causal", "source_pmcid": "PMC12402467" }, { "confidence": "high", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "DOX upregulates Parkin, promoting mitophagy and cardiac injury.", "protein": "Parkin RBR E3 Ubiquitin Protein Ligase (Parkin)", "relationship_type": "causal", "source_pmcid": "PMC12402467" }, { "confidence": "medium", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "Reduced p62 expression indicates increased autophagic flux in DOX-induced injury.", "protein": "Sequestosome 1 (p62)", "relationship_type": "biomarker", "source_pmcid": "PMC12402467" }, { "confidence": "high", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "Increased LC3-II/LC3-I ratio reflects enhanced autophagy in DOX-treated hearts.", "protein": "Microtubule-Associated Proteins 1A/1B Light Chain 3 (LC3)", "relationship_type": "biomarker", "source_pmcid": "PMC12402467" }, { "confidence": "medium", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "DOX increases ULK1, initiating autophagy and contributing to cardiac injury.", "protein": "Unc-51 Like Autophagy Activating Kinase 1 (ULK1)", "relationship_type": "causal", "source_pmcid": "PMC12402467" }, { "confidence": "medium", "disease": "Doxorubicin-induced cardiotoxicity", "glycan_involvement": "Not directly discussed.", "mechanism": "Elevated Beclin-1 indicates increased autophagy in DOX-induced cardiac injury.", "protein": "Beclin-1", "relationship_type": "biomarker", "source_pmcid": "PMC12402467" }, { "confidence": "high", "disease": "Anthracycline-induced myocardial injury", "glycan_involvement": "Glycosylation may affect assay performance.", "mechanism": "cTn-I is recommended for diagnosing anthracycline-induced myocardial injury and guiding therapy.", "protein": "Cardiac Troponin I (cTn-I)", "relationship_type": "biomarker", "source_pmcid": "PMC12402467" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Not directly discussed.", "mechanism": "Modulation of PINK1-mediated mitophagy may protect against heart failure.", "protein": "PTEN-Induced Putative Kinase 1 (PINK1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402467" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Not directly discussed.", "mechanism": "Regulation of Parkin-mediated mitophagy may ameliorate heart failure.", "protein": "Parkin RBR E3 Ubiquitin Protein Ligase (Parkin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402467" }, { "confidence": "high", "disease": "Type 2 Diabetes", "glycan_involvement": "GLP-1 is a glycoprotein; glycosylation may affect stability and receptor interaction.", "mechanism": "GLP-1 stimulates insulin secretion and improves glucose homeostasis; GLP-1 receptor agonists are used for treatment.", "protein": "GLP-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "Short Gut Syndrome (SGS)", "glycan_involvement": "GLP-2 is a glycoprotein; glycosylation may affect half-life and activity.", "mechanism": "GLP-2 promotes intestinal growth and mucosal integrity; GLP-2 analogues improve absorption and reduce parenteral nutrition.", "protein": "GLP-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "Obesity", "glycan_involvement": "PYY is a glycoprotein; glycosylation may affect receptor binding and stability.", "mechanism": "PYY promotes satiety and reduces food intake; reduced PYY may contribute to obesity.", "protein": "PYY", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402511" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Ghrelin is glycosylated; glycosylation may regulate secretion and activity.", "mechanism": "Ghrelin stimulates appetite; levels are paradoxically lower in obesity, possibly due to EEC desensitization.", "protein": "Ghrelin", "protein_enriched": { "function": "Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR) (PubMed:10604470). Induces the release of growth hormone from the pituitary (PubMed:10604470). Has an appetite-stimulating ", "gene_name": "GHRL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9UBU3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402511" }, { "confidence": "medium", "disease": "Type 2 Diabetes", "glycan_involvement": "CCK is glycosylated; glycosylation may affect hormone stability.", "mechanism": "CCK acts as a satiety signal; plasma CCK is reduced in diabetes, impairing satiety regulation.", "protein": "CCK", "relationship_type": "biomarker", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "Not glycosylated, but EEC glycoproteins may regulate 5-HT secretion.", "mechanism": "Increased 5-HT-expressing EECs in IBD; 5-HT modulates motility and inflammation.", "protein": "Serotonin (5-HT)", "relationship_type": "biomarker", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "Chromogranin A is glycosylated; glycosylation may affect secretion and immune modulation.", "mechanism": "Chromogranin A is increased in IBD, reflecting heightened EEC activity.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "Zollinger-Ellison Syndrome", "glycan_involvement": "Gastrin is glycosylated; glycosylation may affect hormone stability.", "mechanism": "Unregulated overproduction of gastrin leads to excessive gastric acid secretion.", "protein": "Gastrin", "protein_enriched": { "function": "Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circu", "gene_name": "GAST", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01350" }, "relationship_type": "causal", "source_pmcid": "PMC12402511" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "IL-32 is glycosylated; glycosylation may modulate cytokine activity.", "mechanism": "EECs express IL-32 in IBD, correlating with inflammation and disease severity.", "protein": "IL-32", "protein_enriched": { "function": "Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis (By similarity)", "gene_name": "WDR55", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H6Y2" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12402511" }, { "confidence": "medium", "disease": "Parkinson's Disease (PD)", "glycan_involvement": "Not glycosylated, but EEC glycoproteins may modulate aggregation or transfer.", "mechanism": "\u03b1-synuclein aggregation in EECs may initiate gut-to-brain spread of pathology.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC12402511" }, { "confidence": "high", "disease": "T-cell acute lymphoblastic leukemia (T-ALL)", "glycan_involvement": "Defective O-glycosylation of TCR and other glycoproteins impairs signaling.", "mechanism": "Mutation in C1GALT1C1 disrupts O-glycosylation, affecting T-cell receptor signaling and contributing to leukemogenesis.", "protein": "C1GALT1C1", "protein_enriched": { "function": "Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance. Associates with the striatin-interacting ", "gene_name": "CTTNBP2", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "Q8WZ74" }, "relationship_type": "causal", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "CRLF2 is a glycoprotein receptor; glycosylation affects receptor stability and signaling.", "mechanism": "Loss of CRLF2 (Xp22.33) associated with proliferative signaling and resistance to cell death in ALL.", "protein": "CRLF2", "protein_enriched": { "function": "Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates", "gene_name": "CRLF2", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "Q9HC73" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "Glycosylation modulates cytokine receptor function.", "mechanism": "Loss of CSF2RA (Xp22.33) linked to impaired cytokine signaling, affecting proliferation and survival.", "protein": "CSF2RA", "protein_enriched": { "function": "Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells", "gene_name": "CSF2RA", "glycan_count": 9, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G49955PK", "G23719VF", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G28541PG", "G12270AG", "G76868JS" ], "uniprot_id": "P15509" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "B-cell acute lymphoblastic leukemia (B-ALL)", "glycan_involvement": "Glycosylation required for receptor surface expression and function.", "mechanism": "Loss of IL3RA (Xp22.33) impacts cytokine-mediated proliferation and angiogenesis.", "protein": "IL3RA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "PXDN is a glycoprotein; glycosylation affects secretion and ECM interaction.", "mechanism": "Gain of PXDN (2p25.3) promotes invasion and metastasis.", "protein": "PXDN", "protein_enriched": { "function": "Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and", "gene_name": "PXDN", "glycan_count": 51, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G02815KT", "G11629QQ", "G15169WU", "G15664MX", "G22310AV", "G25079LO", "G31852PQ", "G41247ZX", "G47748JZ", "G48414YA", "G48584BU", "G55412XP", "G56784JY", "G57888GL", "G62765YT", "G70101JE", "G72747WU", "G73430PD", "G80920RR", "G84452RH", "G87389XI", "G90659AW", "G01650EU", "G02886BB", "G05724UK", "G06110VR", "G10019LZ", "G10486CT", "G18647XP", "G20210JR", "G28541PG", "G37399XV", "G39188ZX", "G39446WN", "G52527GH", "G57776ZU", "G59626AS", "G59924QI", "G64527OM", "G72735IY", "G92050GC", "G57321FI", "G00273SJ", "G25451PN", "G47644PP", "G43417UB", "G25418HZ", "G14260UH", "G82463GQ", "G35107SO", "G49108TO" ], "uniprot_id": "Q92626" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "C-type lectin domain binds glycans; glycosylation critical for ligand recognition.", "mechanism": "Gain of COLEC12 (18p11.32) may modulate immune response and tumor microenvironment.", "protein": "COLEC12", "relationship_type": "biomarker", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "TERT is glycosylated; glycosylation may affect stability and nuclear localization.", "mechanism": "Gain of TERT (5p15.33) drives telomerase activity and immortalization.", "protein": "TERT", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12402711" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "YES1 is a glycoprotein; glycosylation may regulate kinase activity.", "mechanism": "Gain of YES1 (18p11.32) promotes tumorigenesis and metastasis.", "protein": "YES1", "protein_enriched": { "function": "Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by recepto", "gene_name": "YES1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07947" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402711" }, { "confidence": "low", "disease": "Cancer (general)", "glycan_involvement": "USP14 is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Gain of USP14 (18p11.32) may enhance protein degradation pathways in cancer.", "protein": "USP14", "protein_enriched": { "function": "Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins (PubMed:35145029). Ensures the regeneration of ubiquitin at the proteasome (PubMed:181", "gene_name": "USP14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P54578" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402711" }, { "confidence": "high", "disease": "Acute myeloid leukemia (AML)", "glycan_involvement": "AFDN is a cell adhesion glycoprotein; glycosylation affects cell-cell interactions.", "mechanism": "Loss/structural variation of AFDN (6q27) involved in t(6;11) fusion with KMT2A, associated with poor prognosis AML.", "protein": "AFDN", "protein_enriched": { "function": "Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK", "gene_name": "KIDINS220", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G31852PQ" ], "uniprot_id": "Q9ULH0" }, "relationship_type": "causal", "source_pmcid": "PMC12402711" }, { "confidence": "high", "disease": "Burkitt lymphoma", "glycan_involvement": "FASLG is a glycoprotein; glycosylation may affect its stability and cell surface expression, impacting apoptotic signaling.", "mechanism": "FASLG copy number amplification in tumor cells correlates with worse survival, suggesting tumor-mediated killing of T-cells via Fas-FASLG pathway.", "protein": "FASLG (Fas ligand)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "high", "disease": "Breast invasive carcinoma", "glycan_involvement": "Glycosylation of FASLG may modulate its apoptotic activity and interactions with Fas receptor.", "mechanism": "High FASLG copy number in tumor cells correlates with worse survival; high FASLG gene expression (from TILs) correlates with better survival.", "protein": "FASLG (Fas ligand)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "high", "disease": "Autoimmune lymphoproliferative syndrome", "glycan_involvement": "Glycosylation status may affect FASLG function and stability.", "mechanism": "Germline mutations in FASLG cause defective apoptosis, leading to lymphocyte accumulation and autoimmunity.", "protein": "FASLG (Fas ligand)", "relationship_type": "causal", "source_pmcid": "PMC12402715" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "CD200 is a glycoprotein; glycosylation may influence receptor binding and immunosuppressive function.", "mechanism": "Up-regulation of CD200 inhibits T-cell and NK-cell activity, associated with poor survival.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "PD-L1 glycosylation affects its stability and immune evasion capacity.", "mechanism": "PD-L1 expression on tumor cells inhibits T-cell activation; targeted by immune checkpoint inhibitors.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "high", "disease": "Non-small cell lung cancer", "glycan_involvement": "Glycosylation modulates PD-L1 surface expression and function.", "mechanism": "PD-L1 upregulation suppresses T-cell response; blockade improves survival.", "protein": "PD-L1 (CD274)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "CTLA4 glycosylation may affect ligand binding and immune regulation.", "mechanism": "CTLA4 inhibits T-cell activation; blockade enhances anti-tumor immunity.", "protein": "CTLA4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12402715" }, { "confidence": "low", "disease": "Bladder cancer", "glycan_involvement": "Potential involvement due to FASLG glycoprotein nature.", "mechanism": "PRRC2C, a gene adjacent to FASLG, is upregulated in invasive bladder cancer; may indicate increased FASLG expression.", "protein": "FASLG (Fas ligand)", "relationship_type": "biomarker (hypothetical)", "source_pmcid": "PMC12402715" }, { "confidence": "medium", "disease": "Burkitt lymphoma", "glycan_involvement": "Glycosylation may regulate FASLG-mediated apoptosis.", "mechanism": "Tumor FASLG expression may induce apoptosis of infiltrating T-cells, promoting immune evasion.", "protein": "FASLG (Fas ligand)", "relationship_type": "causal", "source_pmcid": "PMC12402715" }, { "confidence": "medium", "disease": "Acute myeloid leukemia", "glycan_involvement": "Glycosylation may affect CD200's immunosuppressive interactions.", "mechanism": "CD200 upregulation correlates with poor prognosis due to immunosuppression.", "protein": "CD200", "protein_enriched": { "function": "Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues", "gene_name": "CD200", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P41217" }, "relationship_type": "biomarker", "source_pmcid": "PMC12402715" }, { "confidence": "medium", "disease": "POLG-related mitochondrial disease", "glycan_involvement": "N-glycosylation regulates chaperone function and stress signaling.", "mechanism": "HSP90B1 upregulation is associated with neurodegeneration and cellular stress response; metformin modulates its expression.", "protein": "HSP90B1", "protein_enriched": { "function": "Involved in synthesis of starch. Catalyzes the synthesis of ADP-glucose, a molecule that serves as an activated glycosyl donor for alpha-1,4-glucan synthesis. Essential for starch synthesis in leaf ch", "gene_name": "AGPL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q688T8" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Mitochondrial myopathy (MT-TA mutation)", "glycan_involvement": "GDF15 is a secreted glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated GDF15 levels indicate mitochondrial dysfunction and disease severity.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Combined oxidative phosphorylation deficiency 25 (COXPD25)", "glycan_involvement": "N-glycosylation may affect mitochondrial import and stability.", "mechanism": "Reduced NDUFB8 expression correlates with Complex I deficiency in MARS2-related disease.", "protein": "NDUFB8", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Combined oxidative phosphorylation deficiency 25 (COXPD25)", "glycan_involvement": "Potential glycosylation impacts mitochondrial function.", "mechanism": "Reduced COXII expression correlates with Complex IV deficiency in MARS2-related disease.", "protein": "COXII", "protein_enriched": { "function": "Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes suc", "gene_name": "MT-CO2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00403" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Primary mitochondrial disease (PMD), MELAS, NPC1, ALS", "glycan_involvement": "Glycosylation may regulate nuclear localization and transcriptional activity.", "mechanism": "MNRR1 activation rescues mitochondrial dysfunction and shifts heteroplasmy below disease threshold.", "protein": "MNRR1 (CHCHD2)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12450258" }, { "confidence": "medium", "disease": "POLG-related mitochondrial disease", "glycan_involvement": "O-glycosylation modulates NOTCH receptor signaling.", "mechanism": "NOTCH pathway upregulation linked to astrocytosis and neuronal loss.", "protein": "NOTCH1", "protein_enriched": { "function": "Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellu", "gene_name": "NOTCH1", "glycan_count": 14, "glycosylation_sites_count": 47, "glytoucan_ids": [ "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G46503DX", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G90659AW", "G49108TO", "G70994MS", "G71142DF", "G26238GL" ], "uniprot_id": "P46531" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Multiple Mitochondrial Dysfunctions Syndrome 1 (MMDS1)", "glycan_involvement": "No direct glycosylation involvement reported.", "mechanism": "NFU1 mutations cause iron-sulfur cluster defects, leading to energy metabolism dysregulation and PAH.", "protein": "NFU1", "protein_enriched": { "function": "Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP)", "gene_name": "PNPO", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NVS9" }, "relationship_type": "causal", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Mitochondrial myopathy (MT-TA mutation)", "glycan_involvement": "Glycosylation affects GDF15 secretion and function.", "mechanism": "GDF15 elevation reflects mitochondrial stress and myopathy.", "protein": "GDF15", "protein_enriched": { "function": "Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (", "gene_name": "GDF15", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G02815KT", "G71784JC", "G49108TO" ], "uniprot_id": "Q99988" }, "relationship_type": "biomarker", "source_pmcid": "PMC12450258" }, { "confidence": "medium", "disease": "POLG-related mitochondrial disease", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "Upregulation associated with neuroinflammation and astrocytosis.", "protein": "JAK-STAT pathway proteins", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "Chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS)", "glycan_involvement": "N-glycosylation may affect mitochondrial import.", "mechanism": "Deficient NDUFB8 activity in muscle correlates with ETC dysfunction in low-heteroplasmy mtDNA deletion syndromes.", "protein": "NDUFB8", "relationship_type": "biomarker", "source_pmcid": "PMC12450258" }, { "confidence": "high", "disease": "PTEN Hamartoma Tumor Syndrome (PHTS)", "glycan_involvement": "PTEN glycosylation may affect stability and signaling in epithelial cells.", "mechanism": "Loss of PTEN function leads to multisystem hamartomas and GI polyposis.", "protein": "PTEN", "protein_enriched": { "function": "Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase", "gene_name": "PTEN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60484" }, "relationship_type": "causal", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "PTEN Hamartoma Tumor Syndrome (PHTS)", "glycan_involvement": "BMPR1A glycosylation modulates receptor function in GI tract.", "mechanism": "Combined PTEN + BMPR1A deletion results in severe GI polyposis and bleeding.", "protein": "BMPR1A", "relationship_type": "causal", "source_pmcid": "PMC12463576" }, { "confidence": "high", "disease": "Gastric Inlet Patch (GIP)", "glycan_involvement": "Aberrant glycosylation distinguishes gastric from esophageal mucosa.", "mechanism": "Presence of gastric mucin glycoproteins (MUC1) in heterotopic tissue confirms GIP.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "Eosinophilic Esophagitis (EoE)", "glycan_involvement": "O-glycosylation changes affect mucosal barrier and inflammation.", "mechanism": "Altered mucin glycoprotein expression in esophageal biopsies is associated with EoE.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "high", "disease": "Gastric Inlet Patch (GIP)", "glycan_involvement": "Glycosylation pattern identifies tissue origin.", "mechanism": "Histological confirmation of gastric-type glycoproteins in esophageal biopsies.", "protein": "Gastric epithelium", "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "Mesenteric Lymphatic Malformation (MLM)", "glycan_involvement": "Glycosylation required for hyaluronan binding and lymphatic function.", "mechanism": "LYVE1 marks lymphatic endothelium in MLM diagnosis.", "protein": "LYVE1", "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "high", "disease": "Celiac Disease", "glycan_involvement": "N-glycosylation modulates IgA stability and immune response.", "mechanism": "IgA anti-tTG used for diagnosis; glycosylation affects antibody function.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "Eosinophilic Esophagitis (EoE)", "glycan_involvement": "Glycosylation influences enzyme activity and tissue deposition.", "mechanism": "Elevated eosinophil granule glycoproteins in esophageal tissue indicate EoE.", "protein": "Eosinophil peroxidase", "protein_enriched": { "function": "This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5", "gene_name": "POR", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G24954UD", "G80920RR", "G49108TO" ], "uniprot_id": "P16435" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "Protein-losing Enteropathy", "glycan_involvement": "N-glycosylation essential for transferrin stability and transport.", "mechanism": "Low serum transferrin reflects protein loss in GI tract.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "medium", "disease": "Protein-losing Enteropathy", "glycan_involvement": "N-glycosylation modulates albumin clearance.", "mechanism": "Hypoalbuminemia due to GI protein loss; glycosylation affects serum half-life.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12463576" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects irisin secretion and stability.", "mechanism": "Serum irisin levels rise with glyco-metabolic stress and correlate with insulin resistance and inflammation.", "protein": "Irisin (FNDC5)", "protein_enriched": { "function": "Mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA", "gene_name": "FNDC5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q8NAU1" }, "relationship_type": "biomarker", "source_pmcid": "PMC12507378" }, { "confidence": "high", "disease": "Hyperinsulinaemic Hypoglycaemia", "glycan_involvement": "Glycosylation may affect immunogenicity and autoantibody formation.", "mechanism": "Autoantibodies against insulin (glycoprotein) cause hypoglycaemia by binding and releasing insulin unpredictably.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "high", "disease": "Doege-Potter Syndrome (NICTH)", "glycan_involvement": "Abnormal glycosylation of IGF-II may enhance its bioactivity.", "mechanism": "Tumor-derived IGF-II (glycoprotein) causes hypoglycaemia by increasing glucose uptake and suppressing endogenous insulin.", "protein": "Insulin-like growth factor II (IGF-II)", "protein_enriched": { "function": "The insulin-like growth factors possess growth-promoting activity (By similarity). Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF2 is influenced b", "gene_name": "IGF2", "glycan_count": 11, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G29931IJ", "G43417UB", "G49108TO", "G57321FI", "G47448YK", "G53434XO", "G58001LT", "G81006GJ", "G29068FM", "G74722FL", "G81295CK" ], "uniprot_id": "P01344" }, "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "medium", "disease": "Childhood Obesity", "glycan_involvement": "Glycosylation modulates ferritin stability and immune recognition.", "mechanism": "Elevated ferritin in obese children reflects chronic inflammation and altered iron metabolism.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC12507378" }, { "confidence": "medium", "disease": "Childhood Obesity", "glycan_involvement": "Glycosylation affects transferrin receptor binding and iron transport.", "mechanism": "Altered transferrin levels indicate iron deficiency in obesity.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12507378" }, { "confidence": "high", "disease": "Congenital Hyperinsulinism", "glycan_involvement": "Glycosylation required for proper channel trafficking and function.", "mechanism": "Mutations in ABCC8 disrupt KATP channel function, causing inappropriate insulin secretion.", "protein": "ABCC8 (SUR1)", "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "medium", "disease": "Hyperinsulinaemic Hypoglycaemia", "glycan_involvement": "N-glycosylation critical for receptor folding and function.", "mechanism": "Mutations in INSR cause abnormal insulin signaling and hypoglycaemia.", "protein": "INR (Insulin receptor)", "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "medium", "disease": "Dent Disease 2", "glycan_involvement": "Glycosylation affects lysosomal targeting and enzyme activity.", "mechanism": "Mutations in OCRL cause proximal tubular dysfunction and rickets.", "protein": "OCRL", "protein_enriched": { "function": "Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic", "gene_name": "OCRL", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q01968" }, "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "high", "disease": "Nephropathic Cystinosis", "glycan_involvement": "Glycosylation required for lysosomal localization and function.", "mechanism": "CTNS mutations impair cystine transport, leading to lysosomal cystine accumulation.", "protein": "CTNS (Cystinosin)", "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "medium", "disease": "MODY5 (HNF1B-associated diabetes)", "glycan_involvement": "Glycosylation may regulate transcription factor stability and nuclear localization.", "mechanism": "HNF1B mutations cause multisystem diabetes and organ malformations.", "protein": "HNF1B", "relationship_type": "causal", "source_pmcid": "PMC12507378" }, { "confidence": "high", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Glycosylation affects NT-proBNP stability and detection.", "mechanism": "Elevated NT-proBNP reflects cardiac wall stress and disease stage.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12531457" }, { "confidence": "high", "disease": "Hypertrophic Cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation modulates peptide clearance and assay sensitivity.", "mechanism": "Higher NT-proBNP levels correlate with advanced HCM stage.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "CD44 glycosylation regulates cell adhesion and migration.", "mechanism": "MSC therapy expressing CD44 delays MMVD progression.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Glycosylation modulates immunomodulatory properties.", "mechanism": "MSC therapy expressing CD90 delays MMVD progression.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Glycosylation affects integrin-mediated signaling.", "mechanism": "MSC therapy expressing CD29 delays MMVD progression.", "protein": "CD29 (Integrin beta-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "Glycosylation may influence myosin function and drug binding.", "mechanism": "Omecamtiv mecarbil targets myosin S1 domain to improve systolic function.", "protein": "Cardiac Myosin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "N-glycosylation modulates ACE activity and stability.", "mechanism": "ACE activity regulates RAAS activation, impacting CHF severity.", "protein": "Angiotensin-Converting Enzyme (ACE)", "relationship_type": "causal", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Restrictive Cardiomyopathy", "glycan_involvement": "Glycosylation affects peptide half-life and detection.", "mechanism": "Elevated natriuretic peptides indicate cardiac dysfunction.", "protein": "Natriuretic Peptides", "relationship_type": "biomarker", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Surface glycoprotein glycosylation critical for MSC function.", "mechanism": "MSC therapy delays progression from stage B1 to B2.", "protein": "CD44/CD90/CD29 (MSC markers)", "relationship_type": "protective", "source_pmcid": "PMC12531457" }, { "confidence": "high", "disease": "Dilated Cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation influences NT-proBNP clearance.", "mechanism": "NT-proBNP levels rise with DCM severity.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC12531457" }, { "confidence": "medium", "disease": "Liver Enzyme Elevation", "glycan_involvement": "AST is N-glycosylated, which affects its stability and secretion.", "mechanism": "AST is measured to monitor liver function during estradiol therapy.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC12544308" }, { "confidence": "medium", "disease": "Liver Enzyme Elevation", "glycan_involvement": "ALT is N-glycosylated, which affects its stability and secretion.", "mechanism": "ALT is measured to monitor liver function during estradiol therapy.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC12544308" }, { "confidence": "high", "disease": "Thrombotic Events", "glycan_involvement": "No direct glycan involvement; effect is via hormone action.", "mechanism": "Oral estradiol increases risk of thrombosis due to first-pass hepatic metabolism.", "protein": "Estradiol", "relationship_type": "causal", "source_pmcid": "PMC12544308" }, { "confidence": "high", "disease": "Liver Enzyme Elevation", "glycan_involvement": "No direct glycan involvement; effect is via hormone action.", "mechanism": "Oral estradiol increases risk of liver enzyme elevation due to first-pass hepatic metabolism.", "protein": "Estradiol", "relationship_type": "causal", "source_pmcid": "PMC12544308" }, { "confidence": "high", "disease": "Gender Dysphoria/Incongruence", "glycan_involvement": "No direct glycan involvement; estradiol is not a glycoprotein.", "mechanism": "Estradiol is used for feminization in transgender women.", "protein": "Estradiol", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12544308" }, { "confidence": "high", "disease": "Acute Pancreatitis", "glycan_involvement": "Lipase is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated serum lipase is a diagnostic biomarker for acute pancreatitis.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545279" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "ALP is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated ALP reflects cholestasis due to bile duct loss.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "AST is glycosylated, which may affect its serum half-life.", "mechanism": "Elevated AST indicates hepatocellular injury in VBDS.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "ALT glycosylation may influence its release during injury.", "mechanism": "ALT elevation signals liver cell damage in VBDS.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "high", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "Albumin glycosylation affects bilirubin transport.", "mechanism": "Elevated bilirubin reflects impaired bile excretion.", "protein": "Total bilirubin (albumin-bound)", "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Vanishing bile duct syndrome (VBDS)", "glycan_involvement": "N-glycosylation of ABCB11 is essential for membrane localization.", "mechanism": "Ursodiol improves bile flow via ABCB11; glycosylation affects transporter function.", "protein": "Ursodeoxycholic acid transporter (ABCB11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Fc glycosylation modulates IgG effector function.", "mechanism": "IgG-mediated immune response damages hepatocytes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Immune-mediated cholangiopathy", "glycan_involvement": "Glycosylation of checkpoint proteins (e.g., PD-1/PD-L1) affects immune recognition.", "mechanism": "Pembrolizumab targets immune checkpoint glycoproteins, leading to immune attack on bile ducts.", "protein": "Cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation may influence ALP activity in lipid metabolism.", "mechanism": "ALP elevation correlates with cholestasis-induced lipid abnormalities.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation of ABCB11 is required for proper function.", "mechanism": "Ursodiol therapy improves lipid profile by restoring bile acid transport.", "protein": "Ursodeoxycholic acid transporter (ABCB11)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12545620" }, { "confidence": "medium", "disease": "Hyperlipidemia", "glycan_involvement": "Albumin glycosylation affects binding capacity for lipids and bilirubin.", "mechanism": "Albumin-bound bilirubin and lipids reflect impaired hepatic clearance.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12545620" }, { "confidence": "high", "disease": "Ectopic ACTH Syndrome (Cushing syndrome)", "glycan_involvement": "Glycosylation affects ACTH stability and secretion.", "mechanism": "Ectopic secretion of glycosylated ACTH by SCLC leads to hypercortisolism.", "protein": "ACTH (Adrenocorticotropic Hormone)", "relationship_type": "causal", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Small Cell Lung Cancer (SCLC)", "glycan_involvement": "Glycosylation may influence ACTH detection and bioactivity.", "mechanism": "Elevated ACTH is a biomarker for paraneoplastic syndrome in SCLC.", "protein": "ACTH (Adrenocorticotropic Hormone)", "relationship_type": "biomarker", "source_pmcid": "PMC12546313" }, { "confidence": "medium", "disease": "Ectopic ACTH Syndrome (Cushing syndrome)", "glycan_involvement": "N-glycosylation regulates CBG affinity for cortisol.", "mechanism": "CBG modulates free cortisol levels in hypercortisolism.", "protein": "Cortisol-binding globulin (CBG)", "relationship_type": "biomarker", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Chemotherapy-induced Immune Hepatitis", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Atezolizumab, a glycosylated antibody, can trigger immune-mediated liver injury.", "protein": "Atezolizumab (anti-PD-L1 antibody)", "relationship_type": "causal", "source_pmcid": "PMC12546313" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects insulin stability and receptor binding.", "mechanism": "Insulin therapy used to manage hyperglycemia exacerbated by hypercortisolism.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Chemotherapy-induced Immune Hepatitis", "glycan_involvement": "Prednisone is not glycosylated but mimics endogenous glycoprotein hormone action.", "mechanism": "Prednisone used to suppress immune-mediated liver injury despite underlying hypercortisolism.", "protein": "Prednisone (synthetic corticosteroid)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Glycosylation may affect ACTH bioactivity.", "mechanism": "Excess ACTH increases cortisol, driving gluconeogenesis and insulin resistance.", "protein": "ACTH (Adrenocorticotropic Hormone)", "relationship_type": "causal", "source_pmcid": "PMC12546313" }, { "confidence": "medium", "disease": "Hypokalemia", "glycan_involvement": "Glycosylation may modulate ACTH receptor interactions.", "mechanism": "ACTH-induced cortisol excess causes mineralocorticoid effects, leading to hypokalemia.", "protein": "ACTH (Adrenocorticotropic Hormone)", "relationship_type": "causal", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Drug-induced Liver Injury (DILI)", "glycan_involvement": "Fc glycosylation influences antibody-mediated immune activation.", "mechanism": "Immune checkpoint inhibitor triggers hepatic immune response.", "protein": "Atezolizumab (anti-PD-L1 antibody)", "relationship_type": "causal", "source_pmcid": "PMC12546313" }, { "confidence": "medium", "disease": "Hyperglycemia", "glycan_involvement": "N-glycosylation alters CBG function and cortisol bioavailability.", "mechanism": "CBG regulates free cortisol, impacting glucose metabolism.", "protein": "Cortisol-binding globulin (CBG)", "relationship_type": "modulator", "source_pmcid": "PMC12546313" }, { "confidence": "high", "disease": "Growth Hormone Deficiency (GHD)", "glycan_involvement": "GH is a glycoprotein; glycosylation affects its stability and receptor binding.", "mechanism": "GH replacement improves growth and metabolic parameters.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12546491" }, { "confidence": "high", "disease": "Small for Gestational Age (SGA)", "glycan_involvement": "Glycosylation modulates GH bioactivity.", "mechanism": "GH therapy promotes catch-up growth and metabolic improvement.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Growth Hormone Deficiency (GHD)", "glycan_involvement": "IGF-1 is N-glycosylated, affecting its half-life.", "mechanism": "IGF-1 levels reflect GH activity and growth response.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "high", "disease": "Impaired Glucose Tolerance", "glycan_involvement": "HbA1c is formed by non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c increases with elevated glucose after GH therapy.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "AST is glycosylated, influencing secretion and stability.", "mechanism": "AST decrease indicates improved liver function after GH therapy.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALT glycosylation affects enzyme activity.", "mechanism": "ALT decrease suggests reduced hepatic stress post-GH treatment.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Apolipoprotein glycosylation modulates lipid transport.", "mechanism": "Total cholesterol decrease reflects improved lipid metabolism after GH therapy.", "protein": "Apolipoproteins (LDL/HDL)", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Metabolic Syndrome", "glycan_involvement": "GH glycosylation impacts metabolic effects.", "mechanism": "GH therapy reduces risk factors (BMI, cholesterol) for metabolic syndrome.", "protein": "Growth Hormone (GH)", "protein_enriched": { "function": "Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati", "gene_name": "GH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01241" }, "relationship_type": "protective", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Small for Gestational Age (SGA)", "glycan_involvement": "N-glycosylation regulates IGF-1 stability.", "mechanism": "IGF-1 mediates growth response to GH in SGA children.", "protein": "IGF-1", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "medium", "disease": "Growth Hormone Deficiency (GHD)", "glycan_involvement": "Reflects glycation status of hemoglobin.", "mechanism": "HbA1c increase in first year may indicate transient glucose intolerance after GH initiation.", "protein": "HbA1c", "relationship_type": "biomarker", "source_pmcid": "PMC12546491" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is glycosylated, affecting its stability and secretion.", "mechanism": "Elevated ALT is used in the Hepatic Steatosis Index (HSI) to screen for NAFLD, which is associated with diminished physical performance and risk of sarcopenia.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "high", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST glycosylation modulates enzyme activity and clearance.", "mechanism": "AST is part of HSI; elevated levels indicate hepatic dysfunction linked to muscle loss and functional decline.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "high", "disease": "Insulin resistance", "glycan_involvement": "Lipoprotein glycosylation affects receptor binding and clearance.", "mechanism": "TyG index (triglyceride-glucose) reflects IR, which impairs muscle metabolism and promotes sarcopenia.", "protein": "Triglyceride-rich lipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation of GLUT is essential for membrane localization and function.", "mechanism": "IR reduces GLUT function, decreasing glucose uptake in muscle and contributing to sarcopenia.", "protein": "Glucose transporter (GLUT)", "relationship_type": "causal", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "N-glycosylation required for receptor folding and signaling.", "mechanism": "Defective glycosylation impairs insulin receptor signaling, promoting IR and muscle protein loss.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Sarcopenic obesity", "glycan_involvement": "O-glycosylation regulates adiponectin multimerization and activity.", "mechanism": "Adiponectin improves insulin sensitivity and reduces inflammation, counteracting sarcopenic obesity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "N-glycosylation affects leptin secretion and receptor binding.", "mechanism": "Leptin resistance in obesity impairs muscle metabolism and may contribute to sarcopenia.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "causal", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Cardiometabolic disease", "glycan_involvement": "N-glycosylation required for enzyme activity.", "mechanism": "Altered lipoprotein lipase activity affects lipid accumulation, contributing to metabolic dysfunction and sarcopenia.", "protein": "Lipoprotein lipase", "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycosylation modulates albumin half-life and function.", "mechanism": "Low serum albumin is associated with frailty and poor physical performance.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "N-glycosylation patterns change during inflammation.", "mechanism": "Altered transferrin glycosylation is linked to inflammation and functional decline in aging.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC12574366" }, { "confidence": "medium", "disease": "Cerebral venous thrombosis (CVT)", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I affects its immunogenicity and interaction with antibodies.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are associated with increased risk of thrombosis, including CVT, by interfering with anticoagulant pathways.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Cerebral venous thrombosis (CVT)", "glycan_involvement": "N-glycosylation is essential for secretion and function of Protein C.", "mechanism": "Protein C is a natural anticoagulant; deficiency increases risk of CVT.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Cerebral venous thrombosis (CVT)", "glycan_involvement": "Glycosylation affects stability and activity of Protein S.", "mechanism": "Protein S acts as a cofactor for Protein C; deficiency predisposes to thrombosis.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Glycan structures modulate antigenicity and antibody binding.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I promote hypercoagulability.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Targets glycoprotein complexes; glycosylation may affect epitope exposure.", "mechanism": "Presence of anti-cardiolipin antibodies is associated with increased risk of thrombosis.", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Altered glycosylation may enhance autoantigenicity.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are common in SLE and contribute to thrombotic risk.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "N-glycosylation required for proper folding and activity.", "mechanism": "Protein C deficiency leads to increased risk of thrombosis.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "protective", "source_pmcid": "PMC12684233" }, { "confidence": "medium", "disease": "Thrombophilia", "glycan_involvement": "Glycosylation affects plasma half-life and function.", "mechanism": "Protein S deficiency increases risk of thrombotic events.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "protective", "source_pmcid": "PMC12684233" }, { "confidence": "low", "disease": "Subdural hematoma", "glycan_involvement": "Glycosylation may modulate immune response and risk.", "mechanism": "Autoantibodies may increase risk of bleeding complications in context of anticoagulation.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12684233" }, { "confidence": "low", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Not directly glycoprotein-related.", "mechanism": "Presence is diagnostic for SLE and may indicate risk for thrombosis.", "protein": "Anti-dsDNA antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12684233" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation modulates stability and localization, impacting function.", "mechanism": "Overexpression promotes GBM growth, proliferation, migration, and EMT via TGF-\u03b2 signaling.", "protein": "Claudin-3", "protein_enriched": { "function": "Barrier-forming claudin. Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity", "gene_name": "CLDN3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15551" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12701664" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation affects extracellular loop interactions and stability.", "mechanism": "Overexpression linked to larger tumor size, poor prognosis, and promotes proliferation/migration via NNAT/Wnt and TGF-\u03b2/TNF-\u03b1/NF-\u03baB pathways.", "protein": "Claudin-4", "protein_enriched": { "function": "Can associate with other claudins to regulate tight junction structural and functional strand dynamics (PubMed:35773259, PubMed:36008380). May coassemble with CLDN8 into tight junction strands contain", "gene_name": "CLDN4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O14493" }, "relationship_type": "causal/biomarker/therapeutic_target", "source_pmcid": "PMC12701664" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation influences membrane localization and barrier function.", "mechanism": "Reduced expression in high-grade gliomas; loss associated with tumor progression and invasiveness.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12701664" }, { "confidence": "high", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation modulates tight junction assembly and barrier properties.", "mechanism": "Reduced expression in advanced gliomas; maintains BBB integrity, loss facilitates tumor invasion.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC12701664" }, { "confidence": "medium", "disease": "Glioblastoma multiforme (GBM)", "glycan_involvement": "Glycosylation may affect developmental regulation and cell surface expression.", "mechanism": "Significantly decreased expression in GBM and lower grade gliomas; potential diagnostic marker.", "protein": "Claudin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12701664" }, { "confidence": "medium", "disease": "Breast cancer brain metastasis", "glycan_involvement": "Glycosylation impacts tight junction formation and barrier function.", "mechanism": "High expression in brain endothelial cells maintains BBB; downregulation increases permeability and facilitates metastasis.", "protein": "Claudin-10", "protein_enriched": { "function": "Forms paracellular channels: coassembles with CLDN19 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellula", "gene_name": "CLDN16", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Y5I7" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12701664" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation may regulate cell surface stability and signaling.", "mechanism": "High expression in aggressive pancreatic cancer cell populations; knockdown inhibits proliferation.", "protein": "Claudin-7", "protein_enriched": { "function": "Plays a major role in tight junction-specific obliteration of the intercellular space", "gene_name": "CLDN7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95471" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12701664" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation modulates cell adhesion and EMT.", "mechanism": "Overexpression associated with advanced stage, lymph node metastasis, and poor prognosis.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12701664" }, { "confidence": "medium", "disease": "Non-small cell lung cancer (NSCLC)", "glycan_involvement": "Glycosylation affects membrane localization and signaling.", "mechanism": "Elevated expression in advanced stages and lymph node metastasis.", "protein": "Claudin-1", "protein_enriched": { "function": "Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermea", "gene_name": "CLDN1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95832" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12701664" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation influences pore formation and drug permeability.", "mechanism": "Elevated expression enhances proliferation; knockdown increases drug sensitivity.", "protein": "Claudin-2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12701664" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation affects antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I are diagnostic for APS and contribute to thrombosis.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "IgG glycosylation modulates immune response and pathogenicity.", "mechanism": "Presence of anticardiolipin IgG is a diagnostic marker for APS.", "protein": "anticardiolipin antibody (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation of IgG influences antibody function.", "mechanism": "Lupus anticoagulant is a diagnostic autoantibody for APS, promoting thrombosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "medium", "disease": "Autoimmune Adrenalitis", "glycan_involvement": "Glycosylation may affect enzyme stability and immunogenicity.", "mechanism": "Autoantibodies against 21-hydroxylase lead to immune-mediated destruction of adrenal cortex.", "protein": "21-hydroxylase", "relationship_type": "causal", "source_pmcid": "PMC12701918" }, { "confidence": "medium", "disease": "Primary Adrenal Insufficiency (PAI)", "glycan_involvement": "IgG glycosylation modulates pathogenicity.", "mechanism": "Presence indicates autoimmune destruction of adrenal cortex causing PAI.", "protein": "anti-21-hydroxylase antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "high", "disease": "Primary Adrenal Insufficiency (PAI)", "glycan_involvement": "ACTH is glycosylated, affecting its stability and receptor interaction.", "mechanism": "Elevated ACTH is a diagnostic marker for PAI due to adrenal failure.", "protein": "adrenocorticotropic hormone (ACTH)", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "medium", "disease": "Primary Adrenal Insufficiency (PAI)", "glycan_involvement": "N-glycosylation affects binding affinity and serum half-life.", "mechanism": "Altered levels reflect changes in cortisol availability in PAI.", "protein": "cortisol-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates inflammatory activity.", "mechanism": "Autoantibodies (IgG) mediate tissue damage in SLE.", "protein": "immunoglobulin G (IgG)", "relationship_type": "causal", "source_pmcid": "PMC12701918" }, { "confidence": "medium", "disease": "Thyroiditis", "glycan_involvement": "IgG glycosylation affects antibody function.", "mechanism": "Presence indicates autoimmune thyroid destruction.", "protein": "anti-thyroid peroxidase antibody", "relationship_type": "biomarker", "source_pmcid": "PMC12701918" }, { "confidence": "medium", "disease": "Catastrophic APS", "glycan_involvement": "Glycosylation modulates antigenicity and immune response.", "mechanism": "Autoantibodies against \u03b22-glycoprotein I drive catastrophic APS and adrenal involvement.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12701918" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "FADD is a glycoprotein; glycosylation may affect its stability and interactions, but specific glycan involvement in this mechanism is not detailed.", "mechanism": "EBPP (Erigeron breviscapus polyphenols plus) and its core fragments covalently bind to FADD at Cys105, triggering immunogenic cell death and plasma membrane rupture in GBM cells.", "protein": "FADD", "protein_enriched": { "function": "Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:240", "gene_name": "FADD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q13158" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12701987" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Caspase-8 is glycosylated; glycosylation may modulate its activation, but direct involvement in this context is not specified.", "mechanism": "Activation of caspase-8 downstream of FADD by EBPP and its core fragments leads to apoptosis and immunogenic cell death in GBM cells.", "protein": "Caspase-8", "protein_enriched": { "function": "Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic devel", "gene_name": "CASP8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14790" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12701987" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "No direct evidence of glycan modification impact in this study.", "mechanism": "Targeting FADD with EBPP prolongs survival in GBM mouse models by 17.6 days, indicating a protective/therapeutic effect.", "protein": "FADD", "protein_enriched": { "function": "Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:240", "gene_name": "FADD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q13158" }, "relationship_type": "protective", "source_pmcid": "PMC12701987" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may affect FADD function, but not directly addressed.", "mechanism": "FADD mediates cell death pathways; its activation by EBPP induces lytic cell death in GBM.", "protein": "FADD", "protein_enriched": { "function": "Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:240", "gene_name": "FADD", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT", "G49108TO" ], "uniprot_id": "Q13158" }, "relationship_type": "causal", "source_pmcid": "PMC12701987" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Not specified.", "mechanism": "Caspase-8 activity increases upon EBPP treatment, serving as a readout for therapeutic efficacy.", "protein": "Caspase-8", "protein_enriched": { "function": "Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic devel", "gene_name": "CASP8", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q14790" }, "relationship_type": "biomarker", "source_pmcid": "PMC12701987" }, { "confidence": "high", "disease": "Multidrug Resistance", "glycan_involvement": "N-glycosylation modulates trafficking and stability.", "mechanism": "Efflux of chemotherapeutic agents from cancer cells, leading to resistance.", "protein": "P-glycoprotein (P-gp)", "relationship_type": "causal", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation affects surface expression and function.", "mechanism": "Efflux transporter contributing to drug resistance in breast cancer.", "protein": "Breast Cancer Resistance Protein (BCRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Biliary Excretion Disorders", "glycan_involvement": "N-glycosylation required for proper localization.", "mechanism": "Loss of MRP2 function impairs biliary excretion of coproporphyrins.", "protein": "MRP2", "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Drug-induced Liver Injury", "glycan_involvement": "N-glycosylation influences transporter activity.", "mechanism": "Inhibition or genetic variation leads to increased plasma levels of CPI and bilirubin.", "protein": "OATP1B1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "N-glycosylation affects substrate specificity.", "mechanism": "Reduced function increases plasma DHEAS and coproporphyrins.", "protein": "OATP1B3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Chronic Renal Failure", "glycan_involvement": "N-glycosylation necessary for membrane localization.", "mechanism": "Reduced OAT1 expression decreases hippuric acid clearance.", "protein": "OAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation impacts transporter stability.", "mechanism": "Altered OAT3 function elevates plasma CPI and GCDCA-S.", "protein": "OAT3", "protein_enriched": { "function": "Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endog", "gene_name": "SLC22A7", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27058EU", "G62765YT" ], "uniprot_id": "Q9Y694" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "medium", "disease": "Adverse Drug Reactions", "glycan_involvement": "N-glycosylation modulates transporter function.", "mechanism": "OCT1 inhibition alters thiamine and IBC levels, affecting drug response.", "protein": "OCT1", "protein_enriched": { "function": "Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immuno", "gene_name": "POU2F1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "P14859" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Transporter-mediated Drug-Drug Interactions", "glycan_involvement": "Indirect, via OATP glycosylation.", "mechanism": "Plasma CPI levels reflect OATP1B activity and DDI risk.", "protein": "Coproporphyrin I (CPI)", "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Hyperbilirubinemia", "glycan_involvement": "Indirect, via OATP glycosylation.", "mechanism": "OATP1B1/1B3 dysfunction increases plasma bilirubin.", "protein": "Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC12702011" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Differential sialylation and fucosylation of N-glycans", "mechanism": "Altered serum N-glycan profiles (H5N4F, H5N4F3SA, H4N5F1SA, H5N4SA2) distinguish CRC patients from healthy controls.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12702213" }, { "confidence": "high", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Loss of fucosylated and sialylated N-glycans", "mechanism": "Downregulation of N-glycans (H5N4F, H5N4F1SA, H4N4F, H5N4) in cancerous tissue compared to paracancerous tissue.", "protein": "Tissue glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12702213" }, { "confidence": "high", "disease": "Stage II colorectal cancer", "glycan_involvement": "Altered N-glycan sialylation/fucosylation", "mechanism": "Significant changes in H4N5F1SA, H5N4F, H5N4F3SA in serum enable early detection of stage II CRC.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12702213" }, { "confidence": "high", "disease": "Stage III colorectal cancer", "glycan_involvement": "Increased sialylation/fucosylation of N-glycans", "mechanism": "Upregulation of H5N4F3SA, H5N4SA2 and further changes in H5N4F in serum mark progression to stage III CRC.", "protein": "Serum glycoproteins (unspecified)", "relationship_type": "biomarker", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "N-glycosylation of CEA", "mechanism": "CEA is a traditional CRC biomarker, but has lower sensitivity and specificity compared to glycan biomarkers.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Adds sialic acid to N-glycans", "mechanism": "Overexpression of ST6GAL1 increases sialylation of serum glycoproteins in CRC.", "protein": "ST6GAL1", "protein_enriched": { "function": "Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CD", "gene_name": "ST6GAL1", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G23770JR", "G36191CD", "G57321FI" ], "uniprot_id": "P15907" }, "relationship_type": "causal", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Adds sialic acid to N-glycans", "mechanism": "Upregulation of ST3GAL4 contributes to increased sialylation of N-glycans in CRC.", "protein": "ST3GAL4", "relationship_type": "causal", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Branched fucosylation of N-glycans", "mechanism": "Abnormal FUT3 expression alters fucosylation patterns in CRC glycoproteins.", "protein": "FUT3", "protein_enriched": { "function": "Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to both the subterminal N-acetyl glucosamine (GlcNAc) of type 1 chain (beta-D-Gal-(1->3)-beta-D-GlcNAc) glycolipids and ", "gene_name": "FUT3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P21217" }, "relationship_type": "causal", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Branched fucosylation of N-glycans", "mechanism": "Abnormal FUT6 expression modulates fucosylation, impacting glycan biomarker levels in CRC.", "protein": "FUT6", "relationship_type": "causal", "source_pmcid": "PMC12702213" }, { "confidence": "medium", "disease": "Colorectal cancer (CRC)", "glycan_involvement": "Core fucosylation of N-glycans", "mechanism": "Altered FUT8 activity reduces core fucosylation, leading to downregulation of core-fucosylated glycans (e.g., H4N5F1SA) in CRC.", "protein": "FUT8", "relationship_type": "causal", "source_pmcid": "PMC12702213" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "FBN1 is a glycoprotein; glycosylation is essential for ECM function and signaling.", "mechanism": "FBN1 mRNA is upregulated in prefrontal cortex in GDM; associated with neuroinflammation and behavioral deficits.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "biomarker", "source_pmcid": "PMC12702234" }, { "confidence": "high", "disease": "Maternal Behavioral Deficits", "glycan_involvement": "Glycosylation affects FBN1 structure and ECM signaling in brain.", "mechanism": "Elevated FBN1 expression correlates with impaired maternal care behaviors in GDM rats.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "causal", "source_pmcid": "PMC12702234" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "Asprosin is a glycoprotein hormone; glycosylation may affect secretion and activity.", "mechanism": "Asprosin, derived from FBN1, is elevated in GDM and modulates glucose metabolism and appetite.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702234" }, { "confidence": "low", "disease": "Maternal Behavioral Deficits", "glycan_involvement": "Glycosylation may regulate asprosin's central effects.", "mechanism": "Elevated asprosin may influence central appetite and stress pathways, potentially affecting maternal motivation.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC12702234" }, { "confidence": "high", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "TNF-\u03b1 is glycosylated; glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "TNF-\u03b1 is significantly elevated in prefrontal cortex and hippocampus in GDM rats.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702234" }, { "confidence": "high", "disease": "Maternal Behavioral Deficits", "glycan_involvement": "Glycosylation affects TNF-\u03b1 bioactivity in CNS.", "mechanism": "Elevated TNF-\u03b1 disrupts serotonin signaling and impairs maternal behaviors.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC12702234" }, { "confidence": "medium", "disease": "Maternal Behavioral Deficits", "glycan_involvement": "SERT is glycosylated; glycosylation modulates transporter function.", "mechanism": "TNF-\u03b1 upregulates SERT, increasing serotonin uptake and reducing synaptic serotonin, leading to behavioral deficits.", "protein": "Serotonin transporter (SERT)", "protein_enriched": { "function": "Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the ", "gene_name": "SLC6A4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31645" }, "relationship_type": "causal", "source_pmcid": "PMC12702234" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "ECM glycosylation influences neuroimmune signaling.", "mechanism": "FBN1 overexpression may exacerbate neuroinflammatory microenvironment in GDM.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "causal", "source_pmcid": "PMC12702234" }, { "confidence": "low", "disease": "Neuroinflammation", "glycan_involvement": "Glycosylation may affect asprosin's inflammatory properties.", "mechanism": "Asprosin may promote inflammatory signaling in CNS, amplifying TNF-\u03b1 production.", "protein": "Asprosin", "protein_enriched": { "function": "Phosphorylates PPP1C, phosphorylase b and CFTR", "gene_name": "LMTK2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G41247ZX", "G23754GO", "G49108TO" ], "uniprot_id": "Q8IWU2" }, "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC12702234" }, { "confidence": "low", "disease": "Mood Disorders (e.g., depression, anxiety)", "glycan_involvement": "Glycosylation impacts FBN1's role in CNS signaling.", "mechanism": "Altered FBN1 expression may contribute to serotoninergic dysfunction and mood disturbances in GDM.", "protein": "Fibrillin-1 (FBN1)", "relationship_type": "biomarker (hypothetical)", "source_pmcid": "PMC12702234" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation modulates adhesion and circulating levels.", "mechanism": "Elevated sICAM-1 reflects endothelial activation and predicts increased CVD risk in PLWH on cART.", "protein": "sICAM-1", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation affects ligand binding and stability.", "mechanism": "Elevated sVCAM-1 indicates endothelial activation and is associated with CVD risk in PLWH on cART.", "protein": "sVCAM-1", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "high", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Elevated hsCRP is a marker of systemic inflammation and predicts CVD risk in PLWH on cART.", "protein": "hsCRP", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "high", "disease": "Monocyte Activation", "glycan_involvement": "N-glycosylation influences receptor shedding and immune signaling.", "mechanism": "Elevated sCD14 reflects monocyte activation and chronic inflammation in PLWH on cART.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Glycosylation 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"Chronic Inflammation", "glycan_involvement": "N-glycosylation modulates receptor shedding and function.", "mechanism": "Elevated sTNFR-2 correlates with inflammation and impaired endothelial function in PLWH on cART.", "protein": "sTNFR-2", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "medium", "disease": "Endothelial Dysfunction", "glycan_involvement": "Extensive glycosylation regulates multimerization and platelet binding.", "mechanism": "Elevated vWF indicates endothelial injury and dysfunction in PLWH on cART.", "protein": "vWF", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "medium", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "N-glycosylation affects secretion and inhibitory activity.", "mechanism": "Elevated PAI-1 reflects impaired fibrinolysis and increased CVD risk in PLWH on cART.", "protein": "PAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC12702278" }, { "confidence": "high", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation affects stability and mitochondrial targeting.", "mechanism": "Artificial organelles reconstruct electron transport chain to restore ATP synthesis in ischemic cardiomyocytes.", "protein": "Cytochrome c", "protein_enriched": { "function": "Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers ", "gene_name": "CYCS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P99999" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation regulates enzyme activity and cellular localization.", "mechanism": "Artificial organelles modulate glycolytic flux to inhibit the Warburg effect and starve tumor cells.", "protein": "Hexokinase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates allosteric regulation.", "mechanism": "Enzyme immobilization in artificial organelles enables precise glycolysis control for cancer therapy.", "protein": "Phosphofructokinase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "N-glycosylation critical for chaperone stability and function.", "mechanism": "Artificial ER mimics deliver chaperones to alleviate ER stress and refold misfolded proteins.", "protein": "Hsp70", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycosylation modulates inter-organelle tethering.", "mechanism": "Artificial organelles mimic ER-mitochondria contacts to restore Ca2+ signaling and ATP production.", "protein": "GRP75 (HSPA9)", "relationship_type": "protective", "source_pmcid": "PMC12702397" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycosylation affects channel gating and mitochondrial import.", "mechanism": "Artificial organelles facilitate Ca2+ transfer to mitochondria, supporting neuronal energy metabolism.", "protein": "VDAC1", "relationship_type": "protective", "source_pmcid": "PMC12702397" }, { "confidence": "medium", "disease": "Neurodegenerative disorders", "glycan_involvement": "Glycosylation influences uniporter assembly and activity.", "mechanism": "Artificial organelles restore mitochondrial Ca2+ uptake, improving ATP synthesis.", "protein": "MCU", "relationship_type": "protective", "source_pmcid": "PMC12702397" }, { "confidence": "high", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation enhances enzyme stability and cellular uptake.", "mechanism": "Artificial peroxisomes co-encapsulate catalase to neutralize pathological ROS surges.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "high", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation improves antioxidant activity and half-life.", "mechanism": "Artificial organelles deliver SOD for multistep ROS scavenging in inflammation.", "protein": "Superoxide dismutase (SOD)", "protein_enriched": { "function": "Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen", "gene_name": "SOD3", "glycan_count": 91, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01485JJ", "G02528FI", "G02815KT", "G03644CB", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10488MI", "G10819WX", "G13131HA", "G14972EH", "G17208MA", "G20528HD", "G20706XG", "G22310AV", "G25079LO", "G27058EU", "G27126ED", "G27947YN", "G28622IK", "G29545VG", "G31852PQ", "G34989PA", "G35541EV", "G37412TK", "G37995HC", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43669FQ", "G44753VC", "G45395BF", "G45504EY", "G46691LC", "G49755GI", "G50856PC", "G55132BD", "G57776ZS", "G58954YZ", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63980BQ", "G64409MC", "G65184UU", "G68490OW", "G69521XL", "G70232NH", "G70441OD", "G70619PT", "G72787SB", "G75568BH", "G76295SF", "G77547TA", "G77669RF", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80479JV", "G80669SJ", "G80920RR", "G81124ET", "G81637OR", "G82443XX", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90575OW", "G90659AW", "G90734RJ", "G92135MA", "G92406TI", "G92551JA", "G93718GY", "G94665LC", "G98611JV", "G43417UB" ], "uniprot_id": "P08294" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates lipid binding and receptor interactions.", "mechanism": "Artificial organelles facilitate lipid transport and breakdown in foam cells to restore lipid homeostasis.", "protein": "Apolipoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702397" }, { "confidence": "high", "disease": "IBD", "glycan_involvement": "N-glycosylation required for proper folding and ligand binding.", "mechanism": "Elevated circulating sICAM-1 reflects endothelial activation/injury and correlates with disease presence.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). 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During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702716" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "Sialylated O-glycans mediate leukocyte rolling.", "mechanism": "sE-selectin is increased in IBD, indicating endothelial activation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702716" }, { "confidence": "medium", "disease": "CD", "glycan_involvement": "Glycosylation required for ligand recognition (e.g., sialyl Lewis X).", "mechanism": "sE-selectin is significantly elevated in CD, especially in active disease.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702716" }, { "confidence": "low", "disease": "IBD", "glycan_involvement": "N-glycosylation modulates integrin binding.", "mechanism": "Trend toward elevated sVCAM-1 in IBD, but not statistically significant.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). 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Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702716" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "N-glycosylation influences integrin \u03b14\u03b27 binding.", "mechanism": "Targeted by vedolizumab to block lymphocyte trafficking; sMAdCAM-1 may reflect treatment response.", "protein": "MAdCAM-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702716" }, { "confidence": "medium", "disease": "IBD", "glycan_involvement": "O-glycosylation and sialylation (sLeX) essential for selectin binding.", "mechanism": "PSGL-1 glycosylation enables selectin-mediated leukocyte rolling, contributing to inflammation.", "protein": "PSGL-1", "protein_enriched": { "function": "A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial step", "gene_name": "SELPLG", "glycan_count": 11, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G45596OR", "G00031MO", "G00978GW", "G25278BX", "G29931IJ", "G59970QL", "G60890ZT", "G63628AV", "G64973KT", "G97345NY" ], "uniprot_id": "Q14242" }, "relationship_type": "causal", "source_pmcid": "PMC12702716" }, { "confidence": "high", "disease": "Pulmonary thromboembolism (PTE)", "glycan_involvement": "Glycosylation is essential for P-glycoprotein's membrane localization and drug transport function.", "mechanism": "P-glycoprotein modulates DOAC plasma concentrations, affecting efficacy and safety in PTE treatment.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Pulmonary thromboembolism (PTE)", "glycan_involvement": "Glycosylation affects CYP3A4 stability and activity.", "mechanism": "CYP3A4 metabolizes DOACs; inhibitors/inducers alter drug levels, impacting PTE management.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12702749" }, { "confidence": "high", "disease": "Pulmonary thromboembolism (PTE)", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation influences its clearance and detection.", "mechanism": "Serial D-dimer levels are used for risk stratification and recurrence prediction in PTE.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702749" }, { "confidence": "high", "disease": "Active cancer", "glycan_involvement": "Glycosylation modulates P-glycoprotein's drug efflux capacity.", "mechanism": "Cancer patients often have altered P-glycoprotein activity, affecting DOAC pharmacokinetics and bleeding/thrombosis risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation of antibodies affects antigen binding and pathogenicity.", "mechanism": "Triple-positive antiphospholipid antibodies increase risk of recurrent thrombosis, impacting DOAC efficacy.", "protein": "Antiphospholipid antibodies (triple-positive)", "relationship_type": "causal", "source_pmcid": "PMC12702749" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation influences D-dimer's immunoreactivity and assay sensitivity.", "mechanism": "Elevated D-dimer indicates active clot formation and is used for VTE diagnosis and monitoring.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Renal impairment", "glycan_involvement": "Glycosylation is critical for P-glycoprotein's function in renal tissue.", "mechanism": "Renal impairment alters P-glycoprotein-mediated drug clearance, affecting DOAC exposure and bleeding risk.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Active cancer", "glycan_involvement": "Glycosylation affects CYP3A4's interaction with substrates and inhibitors.", "mechanism": "Cancer therapies may inhibit or induce CYP3A4, altering DOAC metabolism and safety.", "protein": "CYP3A4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By si", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P79394" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Pulmonary thromboembolism (PTE)", "glycan_involvement": "Glycosylation modulates antibody-mediated thrombogenicity.", "mechanism": "Triple-positive antiphospholipid antibodies predispose to PTE recurrence, challenging DOAC efficacy.", "protein": "Antiphospholipid antibodies (triple-positive)", "relationship_type": "causal", "source_pmcid": "PMC12702749" }, { "confidence": "medium", "disease": "Active cancer", "glycan_involvement": "Glycosylation affects D-dimer's stability and plasma half-life.", "mechanism": "High D-dimer levels in cancer patients indicate increased thrombotic risk and guide anticoagulation decisions.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC12702749" }, { "confidence": "high", "disease": "Tumor recurrence after RFA", "glycan_involvement": "Glycosylation regulates ICAM-1 stability and cell-cell interactions.", "mechanism": "Upregulated on TAECs after IRFA, increases endothelial permeability and platelet activation, promoting tumor cell adhesion and metastasis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "medium", "disease": "Tumor recurrence after RFA", "glycan_involvement": "N-glycosylation modulates VE-cadherin adhesive function.", "mechanism": "Downregulated by ICAM-1/Ezrin interaction post-IRFA, leading to increased endothelial permeability and tumor invasion.", "protein": "VE-cadherin", "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Sialylated glycans on tumor cells interact with E-selectin.", "mechanism": "Upregulated on TAECs after IRFA, enhances adhesion of circulating tumor cells, facilitating metastasis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "medium", "disease": "Tumor recurrence after RFA", "glycan_involvement": "Glycosylation affects EpCAM stability and cell adhesion.", "mechanism": "Upregulated in residual HCC after IRFA, associated with poor prognosis and aggressive phenotype.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702870" }, { "confidence": "high", "disease": "Immunosuppression", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances immune checkpoint function.", "mechanism": "Upregulated on MDSCs post-IRFA, mediates immune evasion and tumor recurrence.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702870" }, { "confidence": "high", "disease": "Tumor recurrence after RFA", "glycan_involvement": "N-glycosylation required for EGFR trafficking and ligand binding.", "mechanism": "m6A-modified EGFR mRNA translation is enhanced post-IRFA, promoting HCC cell survival and metastasis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "medium", "disease": "Tumor metastasis", "glycan_involvement": "Glycosylation affects MMP-9 secretion and activity.", "mechanism": "Upregulated after IRFA, promotes extracellular matrix degradation and tumor invasion.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "high", "disease": "Tumor recurrence after RFA", "glycan_involvement": "Glycosylation modulates VEGF receptor binding.", "mechanism": "Upregulated post-IRFA, drives angiogenesis and supports growth of residual tumor cells.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "medium", "disease": "Tumor recurrence after RFA", "glycan_involvement": "O-glycosylation critical for CD133 epitope recognition.", "mechanism": "Upregulated in residual HCC cells post-IRFA, associated with stemness and invasiveness.", "protein": "CD133", "relationship_type": "biomarker", "source_pmcid": "PMC12702870" }, { "confidence": "high", "disease": "Immunosuppression", "glycan_involvement": "N-glycosylation required for TGF-\u03b22 secretion and activity.", "mechanism": "Upregulated via METTL1-mediated translation post-IRFA, promotes MDSC accumulation and suppresses CD8+ T cells.", "protein": "TGF-\u03b22", "relationship_type": "causal", "source_pmcid": "PMC12702870" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation affects CD109 stability and sEV incorporation.", "mechanism": "Elevated sEV-associated CD109 correlates with ovarian cancer stem cell activity and patient samples.", "protein": "CD109", "protein_enriched": { "function": "Modulates negatively TGFB1 signaling in keratinocytes", "gene_name": "CD109", "glycan_count": 107, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G27058EU", "G00912UN", "G01650EU", "G02815KT", "G08918WF", "G20312EM", "G28541PG", "G31852PQ", "G37399XV", "G41247ZX", "G46503DX", "G62765YT", "G70888PK", "G80920RR", "G92050GC", "G92406TI", "G06356OH", "G07246CJ", "G10486CT", "G10819WX", "G23294PN", "G25451PN", "G27947YN", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G45395BF", "G49906RN", "G57776ZU", "G59536GA", "G59626AS", "G60033FS", "G65184UU", "G66163OV", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G80075MS", "G81263BG", "G84452RH", "G86880BF", "G90659AW", "G00273SJ", "G04657PL", "G10846ZT", "G14972EH", "G20956ZV", "G27126ED", "G40926MX", "G46691LC", "G59334JE", "G74724QE", "G83229XP", "G92135MA", "G05724UK", "G06110VR", "G11629QQ", "G39188ZX", "G41840AI", "G43089EG", "G56784JY", "G57888GL", "G59924QI", "G64527OM", "G08539HC", "G22310AV", "G47748JZ", "G87389XI", "G10019LZ", "G28622IK", "G35107SO", "G38663NM", "G52527GH", "G62461SM", "G62894KT", "G70101JE", "G95865ZB", "G49108TO", "G02528FI", "G80479JV", "G16125XL", "G68490OW", "G83633GK", "G13131HA", "G27915IV", "G37881RL", "G57776ZS", "G59324HL", "G70232NH", "G79666IR", "G83646BJ", "G85282JO", "G87123QX", "G87661QW", "G05962QB", "G52096TR", "G69031IF", "G82443XX", "G20528HD", "G35541EV", "G44753VC", "G50856PC", "G84225JN", "G90382BL", "G93718GY" ], "uniprot_id": "Q6YHK3" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Cancer (general, especially breast, ovarian, lung)", "glycan_involvement": "N-glycosylation modulates EpCAM cell surface expression and sEV sorting.", "mechanism": "EpCAM on sEVs mediates immunosuppression and tumor progression; detected in liquid biopsy.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "N-glycosylation stabilizes PD-L1 and enhances its immunosuppressive function.", "mechanism": "sEV-associated PD-L1 enables immune evasion and is detected in LUAD patient serum.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation regulates HER2 receptor dimerization and sEV packaging.", "mechanism": "sEV HER2 enables detection and staging of HER2-positive breast cancer.", "protein": "HER2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Heavily glycosylated; glycan chains mediate sEV sorting and immune interactions.", "mechanism": "sEV CD24 distinguishes breast cancer-derived EVs from other cell lines.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Extensive O-glycosylation critical for antigenicity and sEV incorporation.", "mechanism": "sEV CA125 detected by SERS immunoassay for ovarian cancer diagnosis.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates EGFR activity and sEV sorting.", "mechanism": "sEV EGFR levels correlate with cancer progression and can be monitored via biosensors.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "O-glycosylation determines MUC1 antigenicity and sEV targeting.", "mechanism": "sEV MUC1 detected by fluorescent aptasensor in gastric cancer cell line-derived EVs.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation affects CLDN3 membrane localization and sEV inclusion.", "mechanism": "sEV CLDN3 identified as a breast cancer marker via WB profiling.", "protein": "CLDN3", "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation modulates ST14 protease activity and sEV sorting.", "mechanism": "sEV ST14 is a potential marker for breast cancer identified by WB.", "protein": "ST14", "protein_enriched": { "function": "Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site (PubMed:10373424). Involved in the terminal differentiation of keratinocytes through prosta", "gene_name": "ST14", "glycan_count": 23, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G31852PQ", "G45395BF", "G83229XP", "G90575OW", "G57321FI", "G04657PL", "G22310AV", "G77669RF", "G80920RR", "G91473PK", "G02815KT", "G05724UK", "G06110VR", "G10486CT", "G39188ZX", "G41247ZX", "G48584BU", "G59626AS", "G62765YT", "G70101JE" ], "uniprot_id": "Q9Y5Y6" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702871" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "CRP is a glycoprotein; its glycosylation affects stability and function in inflammation.", "mechanism": "Elevated CRP reflects systemic inflammation, which promotes endothelial dysfunction and atherosclerosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12702892" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "Increased CRP levels are associated with higher blood pressure and vascular inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12702892" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Reflects total circulating glycosylated acute-phase proteins.", "mechanism": "Elevated glycoprotein acetyls indicate chronic inflammation, correlating with increased CVD risk.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12702892" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ApoB-48's lipoprotein assembly and clearance.", "mechanism": "ApoB-48-containing lipoproteins deposit in arterial walls, promoting foam cell formation and plaque development.", "protein": "Apolipoprotein B-48", "relationship_type": "causal", "source_pmcid": "PMC12702892" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation influences CRP's pro-inflammatory properties.", "mechanism": "High CRP levels are linked to increased stroke risk via vascular inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12702892" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Represents glycosylated inflammatory proteins in circulation.", "mechanism": "Higher glycoprotein acetyls are associated with elevated blood pressure and vascular inflammation.", "protein": "Glycoprotein acetyls", "relationship_type": "biomarker", "source_pmcid": "PMC12702892" }, { "confidence": "low", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates lipoprotein metabolism.", "mechanism": "ApoB-48-rich lipoproteins contribute to cholesterol deposition and CVD progression.", "protein": "Apolipoprotein B-48", "relationship_type": "causal", "source_pmcid": "PMC12702892" }, { "confidence": "high", "disease": "Multidrug resistance", "glycan_involvement": "Glycosylation is essential for P-glycoprotein folding and function.", "mechanism": "Efflux of curcumin and other drugs from intestinal epithelial cells reduces plasma drug concentrations.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates GFAP stability and function.", "mechanism": "GFAP upregulation marks astrocyte activation and neuroinflammation; curcumin nanoencapsulation reduces GFAP levels.", "protein": "Glial fibrillary acidic protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47819" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation affects GST localization and activity.", "mechanism": "Increased GST activity enhances antioxidant defenses in Drosophila and rats treated with curcumin nanocapsules.", "protein": "Glutathione S-transferase", "relationship_type": "protective", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation influences SOD secretion and stability.", "mechanism": "Curcumin nanocapsules increase SOD activity, reducing oxidative stress in inflammation models.", "protein": "Superoxide dismutase", "relationship_type": "protective", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Inflammatory conditions", "glycan_involvement": "Glycosylation modulates catalase activity and cellular localization.", "mechanism": "Catalase activity is upregulated by curcumin nanocapsules, contributing to antioxidant defense.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Albumin glycosylation impacts drug binding and pharmacokinetics.", "mechanism": "Curcumin binds strongly to albumin, affecting its distribution and bioavailability in cancer therapy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Multidrug resistance", "glycan_involvement": "Glycosylation required for transporter function.", "mechanism": "Higher Mdr50 expression in male flies leads to increased efflux of curcumin, reducing drug exposure.", "protein": "Mdr50 (fly ortholog of P-glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation is critical for transporter activity.", "mechanism": "ABC transporters mediate drug efflux, limiting curcumin absorption during inflammation.", "protein": "ABC transporter family", "relationship_type": "causal", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation regulates enzyme activity and substrate specificity.", "mechanism": "Phase II glycoprotein enzymes metabolize curcumin, affecting its anti-atherosclerotic efficacy.", "protein": "Curcumin-conjugating enzymes (UGT/SULT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702928" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Glycosylation changes modulate barrier integrity and drug uptake.", "mechanism": "Inflammation alters glycoprotein expression, impacting curcumin absorption and barrier function.", "protein": "Intestinal epithelial glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC12702928" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation pathway component; impacts glycoprotein biosynthesis.", "mechanism": "Downregulated in MM cells; part of N-glycosylation machinery, potentially affecting glycoprotein folding and secretion.", "protein": "ALG14", "relationship_type": "biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Tyrosine sulfation is a glycan-related post-translational modification affecting glycoprotein function.", "mechanism": "Upregulated in MM; tyrosine sulfation of IFNGR1 modulates immune microenvironment and antigen presentation.", "protein": "TPST2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT1", "glycan_count": 8, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83633GK", "G41247ZX", "G31852PQ", "G62765YT", "G72747WU", "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9Y6A1" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12702948" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Known to be glycosylated, which may affect its cellular localization and function.", "mechanism": "Upregulated in MM; associated with poor prognosis and cell proliferation.", "protein": "ANXA2", "relationship_type": "biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may regulate stability and activity.", "mechanism": "Upregulated in MM; promotes adaptation to hypoxia and tumor progression.", "protein": "HIF1A", "relationship_type": "biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Potential glycosylation may affect protein stability.", "mechanism": "Downregulated in MM; acts as a tumor suppressor by promoting DNA repair and genomic stability.", "protein": "MCPH1", "protein_enriched": { "function": "Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex", "gene_name": "MCPH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NEM0" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "low", "disease": "Multiple Myeloma", "glycan_involvement": "Predicted glycoprotein; glycosylation may affect trafficking.", "mechanism": "Downregulated in MM; may influence lysosomal function and cellular metabolism.", "protein": "PQLC3", "protein_enriched": { "function": "May play a role in the respiratory chain", "gene_name": "C2orf69", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8N8R5" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may modulate nuclear transport activity.", "mechanism": "Upregulated in MM; regulates chromosomal stability and MAPK signaling.", "protein": "RANGAP1", "protein_enriched": { "function": "GTPase activator for RAN (PubMed:16428860, PubMed:8146159, PubMed:8896452). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:2", "gene_name": "RANGAP1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G47950XN" ], "uniprot_id": "P46060" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12702948" }, { "confidence": "low", "disease": "Multiple Myeloma", "glycan_involvement": "Potential glycosylation may affect motor activity.", "mechanism": "Upregulated in MM; promotes proliferation and survival via PI3K/Akt pathway.", "protein": "KIF21B", "protein_enriched": { "function": "Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. Regulates the plus end motility of early endosomes and the balance between ", "gene_name": "KIF16B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q96L93" }, "relationship_type": "biomarker", "source_pmcid": "PMC12702948" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "N-glycosylation and disulfide bonds critical for immunoglobulin folding and secretion.", "mechanism": "MM plasma cells secrete excessive disulfide-rich immunoglobulins, contributing to ER stress and proteostasis imbalance.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC12702948" }, { "confidence": "medium", "disease": "Pancreatic Ductal Adenocarcinoma/Breast Cancer", "glycan_involvement": "Tyrosine sulfation is a glycan-related modification affecting immune signaling.", "mechanism": "Tyrosine sulfation of IFNGR1 by TPST2 modulates tumor immune microenvironment and sensitivity to anti-PD-1 therapy.", "protein": "TPST2", "protein_enriched": { "function": "Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is i", "gene_name": "POMT1", "glycan_count": 8, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G83633GK", "G41247ZX", "G31852PQ", "G62765YT", "G72747WU", "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "Q9Y6A1" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12702948" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "VCAM-1 is N-glycosylated, which is essential for its cell adhesion function.", "mechanism": "HDAC1/2 repress VCAM-1 expression via histone deacetylation, reducing monocyte adhesion and plaque formation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "eNOS is N-glycosylated, affecting its stability and activity.", "mechanism": "SIRT1 deacetylates eNOS, increasing NO production and preserving endothelial function.", "protein": "eNOS (NOS3)", "relationship_type": "protective", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Nectin1 is N-glycosylated, modulating cell-cell adhesion.", "mechanism": "H3K9 lactylation at Nectin1 promoter increases its transcription, promoting angiogenesis in plaques.", "protein": "Nectin1", "protein_enriched": { "function": "Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulati", "gene_name": "CCAR2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q8N163" }, "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Tgfbr2 is N-glycosylated, required for receptor function.", "mechanism": "H3K9 lactylation upregulates Tgfbr2, driving endothelial cell migration and angiogenesis.", "protein": "Tgfbr2", "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "FGF2 is N-glycosylated, influencing secretion and activity.", "mechanism": "Lactylation of YY1 enhances FGF2 transcription, promoting pathological angiogenesis.", "protein": "FGF2", "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "VEGF is glycosylated, affecting receptor binding and angiogenic potency.", "mechanism": "HDAC6 recruited to VEGF promoter, enhancing H3K9 deacetylation and endothelial injury.", "protein": "VEGF", "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ABCA1 is N-glycosylated, required for transporter function.", "mechanism": "HDAC9 represses H3K9 acetylation at ABCA1 promoter, inhibiting cholesterol efflux and promoting foam cell formation.", "protein": "ABCA1", "protein_enriched": { "function": "Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby", "gene_name": "ABCA1", "glycan_count": 12, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G62765YT", "G80920RR", "G83460ZZ", "G60033FS", "G79666IR", "G15664MX", "G70101JE", "G49108TO", "G41071NU", "G57776ZU", "G59626AS" ], "uniprot_id": "O95477" }, "relationship_type": "protective", "source_pmcid": "PMC12702955" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "ABCG1 is N-glycosylated, essential for cholesterol transport.", "mechanism": "HDAC9 represses H3K9 acetylation at ABCG1 promoter, reducing cholesterol efflux.", "protein": "ABCG1", "protein_enriched": { "function": "ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of ", "gene_name": "ABCG5", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H222" }, "relationship_type": "protective", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Diabetic nephropathy", "glycan_involvement": "NLRP3 is glycosylated, influencing inflammasome assembly.", "mechanism": "IGFBP5 promotes NLRP3 inflammasome-induced EndMT via glycolysis-mediated histone lactylation.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC12702955" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "SERPINA3K is N-glycosylated, affecting secretion and inhibitory activity.", "mechanism": "Lactylation at K351 increases SERPINA3K stability, promoting cardiomyocyte survival after ischemia-reperfusion.", "protein": "SERPINA3K", "relationship_type": "protective", "source_pmcid": "PMC12702955" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects its antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are central to APS pathogenesis, leading to thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC12703012" }, { "confidence": "high", "disease": "Pseudo-von Willebrand disease", "glycan_involvement": "Glycosylation is essential for Von Willebrand factor function and clearance.", "mechanism": "Excessive platelet binding accelerates clearance of Von Willebrand factor, reducing its availability and causing bleeding tendency.", "protein": "Von Willebrand factor", "relationship_type": "causal", "source_pmcid": "PMC12703012" }, { "confidence": "medium", "disease": "Aortic thrombosis", "glycan_involvement": "Glycosylation modulates immune recognition and prothrombotic activity.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote arterial thrombosis in APS.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12703012" }, { "confidence": "medium", "disease": "Celiac trunk thrombosis", "glycan_involvement": "Glycosylation influences beta-2 glycoprotein I structure and immune interactions.", "mechanism": "Autoantibody-mediated endothelial dysfunction and thrombosis in APS.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC12703012" }, { "confidence": "medium", "disease": "Aortic thrombosis", "glycan_involvement": "Glycosylation affects stability and function in hemostasis.", "mechanism": "Normal Von Willebrand factor levels help prevent bleeding; reduced levels due to clearance may increase bleeding risk during thrombosis.", "protein": "Von Willebrand factor", "relationship_type": "protective", "source_pmcid": "PMC12703012" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects trafficking and function.", "mechanism": "Efflux transporter upregulation coordinates exclusion of harmful metabolites; dysfunction impairs BBB integration.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12703014" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates transporter stability.", "mechanism": "Coordinated upregulation during metabolic stress and cognitive demand; altered expression linked to BBB dysfunction.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "biomarker", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Blood\u2013brain barrier dysfunction", "glycan_involvement": "Glycosylation stabilizes tight junctions.", "mechanism": "SCFA-induced transcription increases tight junction integrity; LPS/TMAO downregulate expression, increasing permeability.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "causal", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Reduced expression correlates with increased BBB permeability and cognitive decline.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC12703014" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation supports tight junction assembly.", "mechanism": "Downregulation associated with BBB breakdown in AD and TMAO exposure.", "protein": "ZO-1", "protein_enriched": { "function": "TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskelet", "gene_name": "TJP1", "glycan_count": 7, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G99679NM", "G70994MS", "G59324HL", "G28681TP", "G69521XL", "G11942GC" ], "uniprot_id": "Q07157" }, "relationship_type": "biomarker", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation regulates ligand binding and trafficking.", "mechanism": "Integration failure impairs amyloid-\u03b2 clearance, promoting accumulation.", "protein": "LRP1", "relationship_type": "causal", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Blood\u2013brain barrier dysfunction", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Pericyte loss (PDGFR\u03b2 downregulation) destabilizes BBB integration, precedes cognitive symptoms.", "protein": "PDGFR\u03b2", "protein_enriched": { "function": "Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic ", "gene_name": "PDGFRB", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G48414YA", "G38663NM", "G52131KU", "G86500WE", "G49108TO" ], "uniprot_id": "P09619" }, "relationship_type": "biomarker", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "SCFA activation enhances tight junction protein transcription, supporting BBB integrity.", "protein": "GPR41/43", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates ligand recognition.", "mechanism": "LPS/TMAO activation triggers NF-\u03baB signaling, disrupts tight junctions, increases BBB permeability.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC12703014" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Coordinated upregulation during metabolic stress; altered expression reflects BBB integration status.", "protein": "LAT1", "relationship_type": "biomarker", "source_pmcid": "PMC12703014" }, { "confidence": "high", "disease": "Hereditary transthyretin amyloidosis (hATTR)", "glycan_involvement": "Glycosylation affects TTR stability and aggregation propensity.", "mechanism": "Mutant TTR forms amyloid deposits causing neuropathy; siRNA genosome therapy silences TTR expression.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "causal", "source_pmcid": "PMC12703403" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP trafficking and cleavage.", "mechanism": "APP processing leads to amyloid-beta formation; genosome-mediated gene delivery can modulate APP or related pathways.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences ApoE isoform function and amyloid interaction.", "mechanism": "ApoE2 gene delivery via genosomes reduces amyloid burden and improves cognition in AD models.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective/therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation regulates TfR-mediated endocytosis and BBB transport.", "mechanism": "TfR-targeted genosomes deliver genes to CNS, restoring tyrosine hydroxylase activity.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects enzyme stability and localization.", "mechanism": "Gene delivery restores dopamine synthesis in striatal neurons.", "protein": "Tyrosine hydroxylase", "protein_enriched": { "function": "Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopt", "gene_name": "TH", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P07101" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation critical for receptor binding and BBB penetration.", "mechanism": "Used as a targeting ligand on genosomes for enhanced CNS delivery.", "protein": "Rabies virus glycoprotein derivative", "relationship_type": "therapeutic targeting", "source_pmcid": "PMC12703403" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates GLUT1 trafficking and function.", "mechanism": "Genosome surface modification targets GLUT1 for BBB crossing.", "protein": "GLUT1 (SLC2A1)", "relationship_type": "therapeutic targeting", "source_pmcid": "PMC12703403" }, { "confidence": "medium", "disease": "Radiation-induced skin damage", "glycan_involvement": "Potential O-glycosylation may affect protein stability.", "mechanism": "siRNA genosome delivery silences PUMA, reducing apoptosis in skin cells.", "protein": "PUMA (BBC3)", "protein_enriched": { "function": "Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (PubMed:11463391, PubMed:23340338). Promotes partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53, releasing", "gene_name": "BBC3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BXH1" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation required for receptor function and ligand binding.", "mechanism": "Folate-conjugated genosomes enable tumour-specific delivery.", "protein": "Folate receptor", "protein_enriched": { "function": "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, P", "gene_name": "FOLR1", "glycan_count": 68, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G23294PN", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G59536GA", "G60177UT", "G62765YT", "G65184UU", "G66088HZ", "G66163OV", "G68490OW", "G70101JE", "G71051TA", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90382BL", "G92135MA", "G95133RI", "G98611JV", "G99668VU", "G92062TF", "G04657PL", "G05049YU", "G07755XJ", "G10819WX", "G11870QZ", "G13131HA", "G15169WU", "G15664MX", "G20210JR", "G23719VF", "G23984SE", "G31852PQ", "G36379GD", "G42124LM", "G45504EY", "G62894KT", "G70619PT", "G77547TA", "G84225JN", "G90659AW", "G95177YH", "G49108TO" ], "uniprot_id": "P15328" }, "relationship_type": "therapeutic targeting", "source_pmcid": "PMC12703403" }, { "confidence": "high", "disease": "Cancer (pancreatic)", "glycan_involvement": "KRAS is not a glycoprotein; included for context.", "mechanism": "siRNA genosome delivery silences mutant KRAS, reducing tumour growth.", "protein": "KRAS", "relationship_type": "therapeutic target", "source_pmcid": "PMC12703403" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Glycosylation is essential for secretion and stability of s\u03b1Klotho in circulation.", "mechanism": "Serum s\u03b1Klotho levels are upregulated during acute episodes and decrease with treatment; higher admission levels predict better prognosis.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "biomarker", "source_pmcid": "PMC12703584" }, { "confidence": "high", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Glycosylation modulates s\u03b1Klotho's interaction with receptors and proteases.", "mechanism": "s\u03b1Klotho exerts anti-inflammatory, antioxidative, antiapoptotic, and antifibrotic effects, acting as a cardioprotective agent.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "protective", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Chronic Heart Failure", "glycan_involvement": "Glycosylation required for circulating form.", "mechanism": "Lower serum s\u03b1Klotho levels are negatively associated with chronic HF.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "biomarker", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Ischemia/Reperfusion Injury", "glycan_involvement": "Glycosylation enables extracellular release.", "mechanism": "Upregulated s\u03b1Klotho during cardiac cell injury; compensatory release protects against damage.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "protective", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Fibrosis (cardiac/renal)", "glycan_involvement": "Glycosylation affects protein stability and therapeutic efficacy.", "mechanism": "s\u03b1Klotho supplementation protects against fibrosis in animal models.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Low s\u03b1Klotho levels are associated with diabetes and increased cardiovascular risk.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "biomarker", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation essential for circulating form.", "mechanism": "Low s\u03b1Klotho levels correlate with CKD and poor cardiovascular outcomes.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "biomarker", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Aging-related Disorders", "glycan_involvement": "Glycosylation influences serum stability.", "mechanism": "Serum s\u03b1Klotho decreases physiologically with age; reflects biological aging.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "biomarker", "source_pmcid": "PMC12703584" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "s\u03b1Klotho has antitumor activity and may inhibit tumor growth.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12703584" }, { "confidence": "medium", "disease": "Acute Heart Failure (AHF)", "glycan_involvement": "Glycosylation critical for therapeutic formulation.", "mechanism": "Potential for s\u03b1Klotho supplementation or boosting as a therapy to improve prognosis in AHF.", "protein": "\u03b1-Klotho (s\u03b1Klotho)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12703584" }, { "confidence": "high", "disease": "Cancer (multiple types)", "glycan_involvement": "Binds low-molecular-weight hyaluronan (LMW-HA); interacts with glycosylated collagens.", "mechanism": "Elevated layilin promotes tumor invasion, metastasis, and immunosuppression via ECM sensing, NF-\u03baB signaling, and TME modulation.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "biomarker/therapeutic_target/causal", "source_pmcid": "PMC12703705" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "HA binding modulates inflammatory signaling in joint tissues.", "mechanism": "Layilin mediates cartilage degradation and regulates EMT-related proteins in synovial fibroblasts.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12703705" }, { "confidence": "high", "disease": "Fibrosis (renal, organ)", "glycan_involvement": "HA-layilin interaction drives EMT and fibrosis.", "mechanism": "Layilin mediates TNF\u03b1-induced EMT and fibrotic progression in renal disease.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12703705" }, { "confidence": "high", "disease": "Chronic inflammatory diseases", "glycan_involvement": "Specific binding to LMW-HA triggers inflammatory signaling.", "mechanism": "Layilin senses pro-inflammatory ECM signals and modulates immune responses.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12703705" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "HA-layilin axis involved in EMT induction.", "mechanism": "Layilin mediates EMT in glomerular epithelial cells, contributing to disease progression.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "causal", "source_pmcid": "PMC12703705" }, { "confidence": "medium", "disease": "Plastic bronchitis", "glycan_involvement": "Upregulation linked to host-pathogen interaction; HA involvement likely.", "mechanism": "Elevated layilin predicts progression to plastic bronchitis in children with MPP.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "biomarker", "source_pmcid": "PMC12703705" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "HA binding modulates cartilage homeostasis.", "mechanism": "Layilin involved in cartilage degradation in joint disease.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC12703705" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Likely via HA-mediated immune modulation.", "mechanism": "Altered layilin expression in monocytes may contribute to SLE pathogenesis.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC12703705" }, { "confidence": "high", "disease": "Cutaneous wound healing", "glycan_involvement": "HA-layilin signaling regulates immune cell function in wound healing.", "mechanism": "Layilin in Treg cells is essential for tissue repair and skin inflammation control.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "protective", "source_pmcid": "PMC12703705" }, { "confidence": "low", "disease": "Allergic diseases", "glycan_involvement": "Likely via HA binding and immune cell modulation.", "mechanism": "Layilin associated with immune dysregulation in allergy.", "protein": "Layilin", "protein_enriched": { "function": "Receptor for hyaluronate", "gene_name": "LAYN", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G53434XO" ], "uniprot_id": "Q6UX15" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC12703705" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Sphingolipids are glycosylated lipids; glycosylation affects membrane properties.", "mechanism": "Lower plasma levels in pediatric epilepsy with normal brain structure; affects membrane order and neuronal signaling.", "protein": "Dihydrosphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation of sphingolipids modulates neuronal membrane function.", "mechanism": "Altered levels in epilepsy; decreased in acute, increased in chronic epilepsy (animal models); impacts membrane fluidity.", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Terminal glycosylation on glycoproteins; affects cell surface receptor function.", "mechanism": "Lower plasma levels in pediatric epilepsy; stabilizes glycoprotein conformation and cell signaling.", "protein": "N-acetylneuraminate (Sialic acid)", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Associated with glycoprotein-rich membranes; glycosylation may affect lipid-protein interactions.", "mechanism": "Altered levels in epilepsy; component of cell membranes, influences membrane fluidity and signaling.", "protein": "Phosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epileptic hippocampal tissue injury", "glycan_involvement": "GPI anchors glycoproteins to membranes; glycosylation defects disrupt localization and function.", "mechanism": "Altered biosynthesis pathway linked to tissue injury in epilepsy (animal models).", "protein": "Glycosylphosphatidylinositol (GPI)-anchor", "relationship_type": "causal", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epileptic hippocampal tissue injury", "glycan_involvement": "Glycosylation of sphingolipids affects membrane integrity.", "mechanism": "Altered sphingomyelin metabolism associated with hippocampal injury in epilepsy (animal models).", "protein": "Sphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epileptic hippocampal tissue injury", "glycan_involvement": "Terminal glycosylation on glycoproteins; loss affects cell-cell interactions.", "mechanism": "Sialic acid stabilizes glycoproteins; lower levels may impair neuronal adhesion and signaling.", "protein": "N-acetylneuraminate (Sialic acid)", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epileptic hippocampal tissue injury", "glycan_involvement": "Interacts with glycoprotein-rich membranes; glycosylation may modulate lipid-protein dynamics.", "mechanism": "Altered phosphatidylcholine metabolism linked to membrane disruption in epilepsy.", "protein": "Phosphatidylcholine", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epileptic hippocampal tissue injury", "glycan_involvement": "Glycosylation of sphingolipids critical for membrane structure.", "mechanism": "Lower levels may contribute to loss of membrane order and synaptic dysfunction.", "protein": "Dihydrosphingomyelin", "relationship_type": "biomarker", "source_pmcid": "PMC12703977" }, { "confidence": "low", "disease": "Epilepsy", "glycan_involvement": "GPI anchors glycoproteins to neuronal membranes; glycosylation defects may disrupt signaling.", "mechanism": "Altered GPI-anchor biosynthesis pathway implicated in epilepsy pathogenesis (animal models).", "protein": "Glycosylphosphatidylinositol (GPI)-anchor", "relationship_type": "causal", "source_pmcid": "PMC12703977" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation affects PSMA stability and cell surface localization, enhancing tumor targeting.", "mechanism": "PSMA is overexpressed in prostate cancer cells and targeted by nanoparticles for imaging and drug delivery.", "protein": "Prostate-Specific Membrane Antigen", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Altered glycosylation patterns in PSA from cancer patients improve diagnostic specificity.", "mechanism": "PSA levels are used for diagnosis and monitoring; nanoparticle-based sensors detect PSA with high sensitivity.", "protein": "Prostate-Specific Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation modulates N-cadherin-mediated cell adhesion and metastatic potential.", "mechanism": "Magnetic nanoparticles functionalized with N-cadherin antibodies capture circulating tumor cells.", "protein": "N-cadherin", "protein_enriched": { "function": "Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heter", "gene_name": "CDH2", "glycan_count": 37, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G62765YT", "G31916IQ", "G45504EY", "G46220VJ", "G07246CJ", "G11629QQ", "G13131HA", "G14972EH", "G28622IK", "G37881RL", "G40926MX", "G43223CG", "G47748JZ", "G67164EE", "G68490OW", "G83646BJ", "G90382BL", "G49108TO", "G31852PQ", "G35107SO", "G38663NM", "G41247ZX", "G43089EG", "G80920RR", "G02815KT", "G04657PL", "G05049YU", "G28541PG", "G33791AF", "G41071NU", "G57888GL", "G59924QI", "G77547TA", "G85269DF", "G86795LJ", "G87661QW", "G93656SY" ], "uniprot_id": "P19022" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation changes affect apolipoprotein function and cancer progression.", "mechanism": "Serum apolipoprotein levels altered in NMIBC patients; identified via AgNP-assisted proteomics.", "protein": "Apolipoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation regulates complement activation and immune response in tumor microenvironment.", "mechanism": "Complement cascade proteins are differentially expressed in bladder cancer serum.", "protein": "Complement proteins", "relationship_type": "biomarker", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation may influence Bcl-2 stability and apoptotic signaling.", "mechanism": "AgNPs downregulate Bcl-2, promoting apoptosis in bladder cancer cells.", "protein": "Bcl-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation may modulate Bax function in apoptosis.", "mechanism": "AgNPs upregulate Bax, enhancing pro-apoptotic activity in bladder cancer cells.", "protein": "Bax", "protein_enriched": { "function": "Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:3636", "gene_name": "BAX", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q07812" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation can affect caspase-3 activation and apoptotic efficiency.", "mechanism": "AgNPs activate caspase-3, leading to apoptosis in bladder cancer cells.", "protein": "Caspase-3", "protein_enriched": { "function": "Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430).", "gene_name": "CASP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P42574" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Bladder Cancer", "glycan_involvement": "Glycosylation may regulate caspase-7 activity.", "mechanism": "AgNPs activate caspase-7, contributing to apoptosis in bladder cancer cells.", "protein": "Caspase-7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation influences GRPR ligand binding and receptor trafficking.", "mechanism": "GRPR-targeted nanoparticles enable imaging and therapy of GRPR-expressing prostate tumors.", "protein": "GRPR (Gastrin-Releasing Peptide Receptor)", "protein_enriched": { "function": "Receptor for gastrin-releasing peptide (GRP) (PubMed:1655761). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphoryl", "gene_name": "GRPR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P30550" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12704095" }, { "confidence": "high", "disease": "Malignant glioma", "glycan_involvement": "gD glycosylation supports receptor binding specificity.", "mechanism": "Retargeted oHSV-1 using gD modifications to bind IL-13R\u03b12, selectively infecting glioma cells.", "protein": "gD (glycoprotein D)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Melanoma", "glycan_involvement": "Glycosylation maintains gD structure for receptor interaction.", "mechanism": "T-VEC (oHSV-1) uses gD-mediated entry for selective melanoma cell infection.", "protein": "gD (glycoprotein D)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation in gB supports fusogenic activity and ligand insertion.", "mechanism": "gB engineered with anti-HER2 scFv redirects oHSV-1 to HER2+ breast cancer cells.", "protein": "gB (glycoprotein B)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation stabilizes gH/gL structure for receptor binding.", "mechanism": "gH/gL modified with anti-HER2 scFv enables oHSV-1 targeting of HER2+ ovarian cancer cells.", "protein": "gH/gL (glycoprotein H/glycoprotein L complex)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation supports gD folding and ligand display.", "mechanism": "gD modified to target EGFRvIII enables selective infection of glioblastoma cells.", "protein": "gD (glycoprotein D)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Immune evasion (HSV-1)", "glycan_involvement": "O- and N-glycosylation in mucin-like region mediates C3b interaction.", "mechanism": "gC binds complement C3b, inhibiting complement activation and reducing viral clearance.", "protein": "gC (glycoprotein C)", "protein_enriched": { "function": "", "gene_name": "US10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P06486" }, "relationship_type": "causal", "source_pmcid": "PMC12704286" }, { "confidence": "medium", "disease": "Neurological disease (HSV-1 mediated)", "glycan_involvement": "MAG glycosylation supports gB binding.", "mechanism": "MAG acts as a gB receptor in glial cells, facilitating HSV-1 neuroinvasion.", "protein": "MAG (Myelin-associated glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "HSV-1 infection", "glycan_involvement": "N-glycosylation of nectin-1 supports gD interaction.", "mechanism": "Nectin-1 is a primary gD receptor, mediating HSV-1 entry into epithelial and neural cells.", "protein": "Nectin-1", "relationship_type": "causal", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "HSV-1 infection", "glycan_involvement": "Glycosylation stabilizes HVEM for gD binding.", "mechanism": "HVEM serves as a gD receptor, facilitating HSV-1 entry and fusion.", "protein": "HVEM", "relationship_type": "causal", "source_pmcid": "PMC12704286" }, { "confidence": "medium", "disease": "Corneal stromal inflammation", "glycan_involvement": "Glycosylation enhances immunogenicity of gD.", "mechanism": "gD immunization induces immune response, reducing HSV-1-induced corneal inflammation.", "protein": "gD (glycoprotein D)", "relationship_type": "protective", "source_pmcid": "PMC12704286" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and plasma half-life.", "mechanism": "Elevated CRP predicts increased risk, recurrence, and severity of AF; correlates with atrial dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "high", "disease": "Stroke", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "High-sensitivity CRP levels correlate with increased stroke risk in AF patients.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "TNF is glycosylated; glycosylation influences secretion and receptor binding.", "mechanism": "Elevated TNF is associated with chronic AF, atrial fibrosis, and increased left atrial diameter.", "protein": "Tumor necrosis factor", "relationship_type": "causal", "source_pmcid": "PMC12704339" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects TNF's bioactivity.", "mechanism": "TNF upregulated in cardiovascular disease settings, including heart failure.", "protein": "Tumor necrosis factor", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "medium", "disease": "Atrial fibrillation", "glycan_involvement": "IL-2 glycosylation modulates receptor interaction and immune activation.", "mechanism": "Low IL-2 levels are associated with reduced incidence of postoperative AF and successful cardioversion.", "protein": "Interleukin-2", "relationship_type": "protective", "source_pmcid": "PMC12704339" }, { "confidence": "high", "disease": "Atrial fibrillation", "glycan_involvement": "IL-6 glycosylation affects stability and signaling.", "mechanism": "High IL-6 levels correlate with AF presence, duration, recurrence, and post-surgical occurrence.", "protein": "Interleukin-6", "relationship_type": "causal", "source_pmcid": "PMC12704339" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation influences IL-6's inflammatory potency.", "mechanism": "High serum IL-6 independently associated with stroke and mortality in AF patients.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates IL-6 secretion and receptor binding.", "mechanism": "IL-6 produced by ischaemic cardiomyocytes; involved in acute-phase response in heart failure.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation critical for CRP's solubility and function.", "mechanism": "Elevated CRP linked to inflammation in heart failure and atrial dysfunction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Glycosylation affects TNF's inflammatory signaling.", "mechanism": "TNF upregulation contributes to vascular inflammation and stroke risk in AF.", "protein": "Tumor necrosis factor", "relationship_type": "biomarker", "source_pmcid": "PMC12704339" }, { "confidence": "high", "disease": "NSCLC", "glycan_involvement": "Glycosylation stabilizes PD-L1 and affects immune evasion.", "mechanism": "PD-L1 blockade via liposomal co-delivery enhances immunogenicity and inhibits tumor/metastatic growth.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "high", "disease": "Hodgkin lymphoma", "glycan_involvement": "N-glycosylation required for MHC-I surface expression.", "mechanism": "DNMT inhibitors upregulate MHC-I, improving antigen presentation and response to checkpoint inhibitors.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "NSCLC", "glycan_involvement": "EGFR glycosylation modulates ligand binding and drug sensitivity.", "mechanism": "HDAC inhibitors reverse resistance to EGFR-TKIs, promoting apoptosis.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "O-glycosylation affects CD45 function and immune signaling.", "mechanism": "PEI-EZH2 siRNA complexes reduce CD45+/CD11b+ AML populations.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "AML", "glycan_involvement": "N-glycosylation modulates integrin-mediated adhesion.", "mechanism": "Reduction in CD11b+ cells correlates with AML suppression.", "protein": "CD11b", "protein_enriched": { "function": "Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By simil", "gene_name": "Itgam", "glycan_count": 7, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G64527OM", "G80920RR", "G62765YT", "G39188ZX", "G70101JE", "G70232NH", "G49108TO" ], "uniprot_id": "P05555" }, "relationship_type": "biomarker", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "Potential O-glycosylation affects RNA-binding activity.", "mechanism": "EV-based YTHDF1 siRNA delivery suppresses tumor progression via m6A-dependent regulation.", "protein": "YTHDF1", "protein_enriched": { "function": "Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability (PubMed:24284625, PubMed:26318451, PubMed:32492408, PubMed:39900921). M6A is a modification p", "gene_name": "YTHDF1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "Q9BYJ9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "Triple-negative breast cancer", "glycan_involvement": "Glycosylation may regulate FOXM1 stability.", "mechanism": "Nanoemulsion co-delivery of decitabine/panobinostat reduces FOXM1 expression by 80%.", "protein": "FOXM1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "BRD4 glycosylation may affect chromatin binding.", "mechanism": "BET inhibitors disrupt BRD4-chromatin interaction, suppressing oncogenic transcription.", "protein": "BRD4", "protein_enriched": { "function": "Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation (PubMed:20871596, Pu", "gene_name": "BRD4", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O60885" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "medium", "disease": "Follicular lymphoma", "glycan_involvement": "Glycosylation may modulate EZH2 stability/activity.", "mechanism": "EZH2 inhibitors suppress tumorigenesis and stem-like transcriptional reprogramming.", "protein": "EZH2", "protein_enriched": { "function": "Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affec", "gene_name": "EZH2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q15910" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704357" }, { "confidence": "high", "disease": "Peripheral T-cell lymphoma", "glycan_involvement": "N-glycosylation critical for HLA-A antigen presentation.", "mechanism": "Epigenetic drugs enhance HLA-A expression, improving immune recognition.", "protein": "HLA-A", "protein_enriched": { "function": "Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells fo", "gene_name": "HLA-A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P04439" }, "relationship_type": "biomarker", "source_pmcid": "PMC12704357" }, { "confidence": "high", "disease": "Stunting", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and function as an inflammatory marker.", "mechanism": "Elevated CRP indicates systemic inflammation, which is associated with increased risk of stunting in infants.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "high", "disease": "Stunting", "glycan_involvement": "AGP is heavily N-glycosylated; glycan changes modulate its anti-inflammatory properties.", "mechanism": "Higher AGP levels are associated with reduced height-for-age Z-scores, indicating a link between inflammation and impaired growth.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Altered glycosylation in AGP may reflect or drive inflammatory status.", "mechanism": "Malnourished children show higher AGP concentrations, reflecting chronic inflammation.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "CRP glycosylation affects its clearance and inflammatory signaling.", "mechanism": "Elevated CRP is observed in malnourished children, indicating systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "medium", "disease": "Stunting", "glycan_involvement": "IGFBP3 is N-glycosylated, which modulates its binding affinity for IGF-1.", "mechanism": "Lower IGFBP3 levels are associated with impaired growth and stunting; regulates IGF-1 bioavailability.", "protein": "IGF binding protein 3", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "low", "disease": "Low birth weight", "glycan_involvement": "Glycosylation of IGFBP3 affects its stability and IGF-1 interaction.", "mechanism": "Altered IGFBP3 levels may reflect disrupted growth factor signaling in LBW infants.", "protein": "IGF binding protein 3", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "low", "disease": "Small for gestational age", "glycan_involvement": "N-glycosylation modulates IGFBP3 function.", "mechanism": "Lower IGFBP3 may be linked to SGA via reduced IGF-1 bioactivity.", "protein": "IGF binding protein 3", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "medium", "disease": "Stunting", "glycan_involvement": "Not glycosylated; regulated by glycoprotein IGFBP3.", "mechanism": "Lower IGF-1 levels are associated with impaired linear growth and stunting.", "protein": "Insulin-like growth factor 1", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "medium", "disease": "Non-communicable diseases", "glycan_involvement": "CRP glycosylation influences its inflammatory activity.", "mechanism": "Persistent low-grade inflammation (high CRP) in early life increases risk for NCDs.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "low", "disease": "Non-communicable diseases", "glycan_involvement": "AGP glycosylation patterns change in chronic disease states.", "mechanism": "Chronic elevation of AGP is linked to increased NCD risk via sustained inflammation.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC12704893" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "GP130 is a glycoprotein; glycosylation is required for proper cell surface expression and ligand binding.", "mechanism": "GP130 mediates IL-6-induced JAK/STAT3 signaling, promoting tumor cell survival and proliferation.", "protein": "GP130", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704912" }, { "confidence": "high", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "IL-6 is glycosylated, which affects its stability and receptor interactions.", "mechanism": "IL-6 activates GP130/JAK/STAT3 pathway, driving tumorigenesis and progression.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Glycosylation of IL-6R\u03b1 is essential for receptor function.", "mechanism": "IL-6R\u03b1 dimerizes with GP130 upon IL-6 binding, initiating downstream oncogenic signaling.", "protein": "IL-6R\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation status may modulate receptor activity and downstream signaling.", "mechanism": "Higher GP130 pathway activation correlates with glucose metabolism disturbances in PDAC patients.", "protein": "GP130", "relationship_type": "biomarker", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects IL-6 secretion and bioactivity.", "mechanism": "IL-6 promotes adipose tissue inflammation, impairs insulin sensitivity, and correlates with hyperglycemia.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Autotaxin is a glycoprotein; glycosylation influences its enzymatic activity.", "mechanism": "IL-6/GP130/JAK/STAT3 activation upregulates autotaxin in adipocytes, contributing to insulin resistance.", "protein": "Autotaxin", "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation modulates autotaxin function.", "mechanism": "Genetic suppression of autotaxin improves insulin sensitivity and reduces hepatic steatosis.", "protein": "Autotaxin", "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "Glycosylation may affect GP130-mediated signaling in cachexia.", "mechanism": "GP130/IL-6 pathway activation is associated with cancer cachexia in PDAC.", "protein": "GP130", "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "low", "disease": "Neural invasion in PDAC", "glycan_involvement": "Glycosylation required for GP130 function.", "mechanism": "IL-6/GP130/JAK/STAT3 axis implicated in neural invasion and disease progression.", "protein": "GP130", "relationship_type": "causal", "source_pmcid": "PMC12704912" }, { "confidence": "medium", "disease": "Pancreatic ductal adenocarcinoma (PDAC)", "glycan_involvement": "Integrin \u03b23 is a glycoprotein; glycosylation affects cell adhesion and signaling.", "mechanism": "Integrin \u03b23 expression is upregulated downstream of IL-6/STAT3 and associated with prognosis.", "protein": "Integrin \u03b23", "relationship_type": "biomarker", "source_pmcid": "PMC12704912" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Potential gain of N-glycosylation at N437 (G433E mutation) may alter protein interactions.", "mechanism": "PLK1 overexpression correlates with poor prognosis and survival; missense mutations destabilize structure and function.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Liver cancer", "glycan_involvement": "No direct evidence; possible indirect effects via structural changes.", "mechanism": "PLK1 overexpression associated with poor overall survival.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "high", "disease": "Lung cancer", "glycan_involvement": "No direct evidence; possible indirect effects via altered PTM accessibility.", "mechanism": "PLK1 overexpression and specific mutations (e.g., R293H) linked to poor prognosis and altered cell cycle regulation.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC12704984" }, { "confidence": "high", "disease": "Kidney cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 overexpression strongly correlates with poor survival (HR=6.69).", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 overexpression associated with reduced survival.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Bladder cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 R175P mutation identified in bladder cancer; destabilizes protein structure.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "high", "disease": "Colon cancer", "glycan_involvement": "G433E mutation predicted to induce N-glycosylation at N437.", "mechanism": "PLK1 mutations (R293C, R293H, G422R, G433E, A520T) found in colon cancer; impact protein stability and interactions.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Endometrial cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 mutations (R175Q, L188P, F304V, A520T) identified; destabilize structure.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Esophageal cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 R293C mutation found in esophageal cancer; impacts protein function.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "medium", "disease": "Uterine cancer", "glycan_involvement": "No direct evidence.", "mechanism": "PLK1 mutations (R175Q, L188P, F304L, F304V, A520T) identified; affect protein folding and function.", "protein": "Polo-like kinase 1 (PLK1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC12704984" }, { "confidence": "high", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "Predicted glycosylation (signal peptide, Golgi localization) may facilitate envelope formation and immune evasion.", "mechanism": "Highly expressed transmembrane glycoprotein involved in virion assembly and envelope acquisition during lytic infection.", "protein": "ORF80", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "Transmembrane domain suggests glycosylation important for membrane integration.", "mechanism": "Transmembrane glycoprotein, highly expressed during infection, likely contributes to virion structure and host cell interaction.", "protein": "ORF88", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "Transmembrane localization implies glycosylation role in function.", "mechanism": "Transmembrane glycoprotein, highly expressed, may be involved in virion assembly or host immune modulation.", "protein": "ORF111", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "Signal peptide and extracellular localization suggest N-glycosylation for secretion and immune evasion.", "mechanism": "Extracellular glycoprotein with signal peptide, highly expressed late in infection, possibly involved in virion release.", "protein": "ORF13", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "high", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct glycosylation evidence, but may interact with glycoproteins during replication.", "mechanism": "dUTPase-like protein, highly expressed, marks active viral replication and lytic phase.", "protein": "ORF27", "relationship_type": "biomarker", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct evidence, but may process glycoproteins during maturation.", "mechanism": "Putative capsid maturation protease, highly expressed, essential for virion assembly.", "protein": "ORF107", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "low", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct evidence, but possible glycan-mediated interactions.", "mechanism": "Protein with disordered region, highly expressed, may facilitate viral assembly or host interaction.", "protein": "ORF45", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct evidence, but may interact with glycosylated host receptors.", "mechanism": "Apoptosis inhibitor, overexpressed in high-susceptibility oysters, promotes cell survival for viral replication.", "protein": "ORF42", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "medium", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct evidence, but may interact with host glycoproteins.", "mechanism": "Apoptosis inhibitor, overexpressed in high-susceptibility oysters, facilitates persistent infection.", "protein": "ORF99", "relationship_type": "causal", "source_pmcid": "PMC12705076" }, { "confidence": "low", "disease": "Ostreid herpesvirus 1 (OsHV-1) infection", "glycan_involvement": "No direct evidence.", "mechanism": "Nuclear protein, immediate-early expression, marks onset of infection.", "protein": "ORF122", "relationship_type": "biomarker", "source_pmcid": "PMC12705076" }, { "confidence": "high", "disease": "Melanosome biogenesis defects", "glycan_involvement": "Pmel17 is a glycoprotein; glycosylation may regulate folding and amyloid formation.", "mechanism": "Mutation or disruption of Pmel17 M\u03b1 amyloid formation impairs melanin synthesis and increases cellular toxicity.", "protein": "Pmel17", "relationship_type": "causal", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Protein-conformation disorders", "glycan_involvement": "Glycosylation may facilitate proper folding and rapid amyloid formation.", "mechanism": "Rapid amyloid formation by Pmel17 M\u03b1 avoids toxic intermediates typical in pathogenic amyloid formation.", "protein": "Pmel17", "relationship_type": "protective", "source_pmcid": "PMC1288040" }, { "confidence": "high", "disease": "Alzheimer disease", "glycan_involvement": "Not specified in this article.", "mechanism": "A\u03b2 forms amyloid fibrils that aggregate into plaques, leading to neurodegeneration.", "protein": "A\u03b2 (Amyloid-beta)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC1288040" }, { "confidence": "high", "disease": "Parkinson disease", "glycan_involvement": "Not specified in this article.", "mechanism": "\u03b1-synuclein forms amyloid fibrils that aggregate, contributing to neurodegeneration.", "protein": "\u03b1-synuclein", "relationship_type": "causal", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Alzheimer disease", "glycan_involvement": "Glycosylation may regulate amyloid formation speed.", "mechanism": "Pmel17 M\u03b1 amyloid formation is much faster than A\u03b2, suggesting a mechanism to avoid toxic intermediates seen in Alzheimer disease.", "protein": "Pmel17", "relationship_type": "protective", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Parkinson disease", "glycan_involvement": "Glycosylation may regulate amyloid formation speed.", "mechanism": "Pmel17 M\u03b1 amyloid formation avoids toxic intermediates, unlike \u03b1-synuclein in Parkinson disease.", "protein": "Pmel17", "relationship_type": "protective", "source_pmcid": "PMC1288040" }, { "confidence": "low", "disease": "Huntington disease", "glycan_involvement": "Glycosylation may regulate amyloid formation.", "mechanism": "Functional amyloid formation by Pmel17 may inform mechanisms to avoid toxicity in Huntington disease.", "protein": "Pmel17", "relationship_type": "protective", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Protein-conformation disorders", "glycan_involvement": "Glycosylation may be a target for modulating amyloid formation.", "mechanism": "Understanding Pmel17 amyloid formation may guide therapies to prevent toxic intermediates in protein-conformation disorders.", "protein": "Pmel17", "relationship_type": "therapeutic_target", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Melanosome biogenesis defects", "glycan_involvement": "Glycosylation status may affect biomarker reliability.", "mechanism": "Presence of Pmel17 amyloid fibrils indicates normal melanosome biogenesis.", "protein": "Pmel17", "relationship_type": "biomarker", "source_pmcid": "PMC1288040" }, { "confidence": "medium", "disease": "Pigmentation disorder", "glycan_involvement": "Glycosylation may be required for proper amyloid formation and melanin synthesis.", "mechanism": "Defective Pmel17 amyloid formation leads to reduced melanin synthesis and pigmentation defects.", "protein": "Pmel17", "relationship_type": "causal", "source_pmcid": "PMC1288040" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Aberrant O-glycosylation exposes core protein, affecting immune recognition.", "mechanism": "Overexpression and altered glycosylation of MUC-1 correlates with tumor progression and immune evasion.", "protein": "MUC-1", "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Altered N-glycosylation increases stability and immune escape.", "mechanism": "Elevated serum CEA is used for diagnosis and monitoring of colorectal cancer.", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "high", "disease": "Head and neck squamous cell carcinoma", "glycan_involvement": "N-glycosylation affects receptor dimerization and signaling.", "mechanism": "EGFR overexpression drives proliferation; glycosylation modulates ligand binding and receptor activation.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC2441959" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates receptor conformation and drug response.", "mechanism": "HER2 overexpression promotes aggressive tumor growth; glycosylation impacts antibody binding (trastuzumab).", "protein": "HER2/neu (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC2441959" }, { "confidence": "medium", "disease": "Invasive ductal carcinoma", "glycan_involvement": "Heparan sulfate chains mediate cell-matrix interactions.", "mechanism": "Syndecan-1 expression correlates with tumor invasiveness and poor prognosis.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "medium", "disease": "Oesophageal cancer", "glycan_involvement": "Glycosylation regulates integrin binding and cell adhesion.", "mechanism": "Laminin-332 promotes tumor cell migration and invasion.", "protein": "Laminin-332", "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "medium", "disease": "Biliary tract cancer", "glycan_involvement": "Altered O-glycosylation affects viscosity and tumor microenvironment.", "mechanism": "Mucin glycoprotein levels are elevated in biliary tract cancer.", "protein": "Mucin glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "high", "disease": "Renal cell carcinoma", "glycan_involvement": "N-glycosylation required for secretion and receptor binding.", "mechanism": "VEGF drives angiogenesis in renal cell carcinoma.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC2441959" }, { "confidence": "medium", "disease": "Oral squamous cell carcinoma", "glycan_involvement": "N-glycosylation modulates cell adhesion and immune interactions.", "mechanism": "ICAM2 expression is associated with tumor progression.", "protein": "ICAM2", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM2 may play a role in lymphocyte recirculation by blocking LFA-1-dependent cell adhesion. It mediates a", "gene_name": "ICAM2", "glycan_count": 26, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G62765YT", "G22310AV", "G31852PQ", "G52527GH", "G80920RR", "G84452RH", "G11629QQ", "G37399XV", "G57888GL", "G82463GQ", "G31665QC", "G43089EG", "G47518TP", "G56784JY", "G75983OB", "G15169WU", "G24528MX", "G39619TI", "G43769HG", "G45395BF", "G57776ZS", "G82830MN", "G49108TO" ], "uniprot_id": "P13598" }, "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "N-glycosylation affects protein stability and secretion.", "mechanism": "NGAL is upregulated in pancreatic cancer and correlates with poor prognosis.", "protein": "Lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC2441959" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans; cleavage alters glycan-binding and function.", "mechanism": "MMP cleavage of galectin-3 promotes chemotaxis, invasion, angiogenesis, and metastasis.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Prostate Cancer", "glycan_involvement": "Glycan-binding activity modulated by cleavage.", "mechanism": "Cleavage by MMPs enhances tumor progression and angiogenesis.", "protein": "Galectin-3", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Heavily glycosylated; glycosylation required for MCT chaperone function.", "mechanism": "Stabilizes MCT-1/4 on membrane, promoting glycolysis and tumor survival under hypoxia.", "protein": "Basigin (CD147)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC2756345" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation affects membrane localization and stability.", "mechanism": "Acidifies extracellular milieu, promotes migration, survival, and growth in hypoxic tumors.", "protein": "Carbonic Anhydrase IX (CAIX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Glycosylation modulates cell-cell adhesion and signaling.", "mechanism": "Regulates sensitivity of Ph+ ALL cells to apoptosis.", "protein": "VE-cadherin", "relationship_type": "biomarker", "source_pmcid": "PMC2756345" }, { "confidence": "high", "disease": "Colitis Associated Cancer", "glycan_involvement": "Cleaves heparan sulfate glycosaminoglycans.", "mechanism": "Promotes tumorigenesis by remodeling extracellular matrix and releasing growth factors.", "protein": "Heparanase", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Binds galectin-3 via glycan-dependent interactions.", "mechanism": "Stimulates IL-6 expression in tumor microenvironment, promoting tumor progression.", "protein": "Galectin-3 Binding Protein", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Glioma", "glycan_involvement": "Glycosylation modulates ECM interactions and cell signaling.", "mechanism": "Overexpressed in glioma-associated vessels, stimulates angiogenesis.", "protein": "Tenascin-C", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Head and Neck Squamous Cell Carcinoma", "glycan_involvement": "Glycosylation required for integrin binding and ECM assembly.", "mechanism": "Autocrine fibronectin essential for matrix assembly and cell adhesion.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "protective", "source_pmcid": "PMC2756345" }, { "confidence": "medium", "disease": "Melanoma", "glycan_involvement": "Glycosylation affects cell adhesion and signaling.", "mechanism": "Links inflammation with melanoma metastasis via PAR1-PAFR-MUC18 pathway.", "protein": "MUC18 (CD146)", "relationship_type": "causal", "source_pmcid": "PMC2756345" }, { "confidence": "high", "disease": "CNS vasculitis", "glycan_involvement": "Glycosylation of beta2-glycoprotein I affects its antigenicity and autoantibody binding.", "mechanism": "High titers of anti-beta2-glycoprotein I antibodies are strongly associated with CNS vasculitis in SLE patients.", "protein": "beta2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC3194614" }, { "confidence": "high", "disease": "Neuropsychiatric SLE (CNS lupus)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Presence of anti-beta2-glycoprotein I antibodies correlates with neuropsychiatric manifestations in SLE.", "protein": "beta2-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC3194614" }, { "confidence": "medium", "disease": "CNS vasculitis", "glycan_involvement": "Targets glycoprotein complexes; glycosylation may affect epitope exposure.", "mechanism": "High anticardiolipin antibody titers are associated with CNS vasculitis in SLE.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC3194614" }, { "confidence": "medium", "disease": "Epstein-Barr Virus (EBV) encephalitis", "glycan_involvement": "Therapeutic glycoprotein; Fc glycosylation affects efficacy.", "mechanism": "Rituximab was effective in treating EBV encephalitis in SLE patient.", "protein": "Rituximab (anti-CD20 monoclonal antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC3194614" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Fc glycosylation modulates antibody-dependent cellular cytotoxicity.", "mechanism": "Rituximab improved severe SLE symptoms and resolved lupus nephritis.", "protein": "Rituximab (anti-CD20 monoclonal antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC3194614" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "gp120 is heavily glycosylated; glycosylation is essential for its structure and function, and nanoparticle binding may interfere with glycan-mediated interactions.", "mechanism": "Silver nanoparticles bind to disulfide bond regions of the CD4 binding domain within gp120, inhibiting viral binding to host cells.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC3244796" }, { "confidence": "medium", "disease": "HSV infection", "glycan_involvement": "IgM is heavily glycosylated; glycosylation may affect stability and immune recognition.", "mechanism": "Lower serum IgM levels observed in HIV patients with HSV coinfection.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "HSV infection + VH", "glycan_involvement": "Glycosylation may modulate IgM function in coinfection.", "mechanism": "IgM levels are significantly lower in patients with both HSV and VH compared to those without.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "Candidiasis (absence)", "glycan_involvement": "IgA glycosylation affects mucosal immunity and pathogen binding.", "mechanism": "Higher IgA levels found in HIV patients without candidiasis.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "Oral candidiasis", "glycan_involvement": "IgG glycosylation modulates effector functions and pathogen clearance.", "mechanism": "Lower IgG concentration in patients with oral candidiasis compared to other candidiasis localizations.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "Candidiasis (other localizations)", "glycan_involvement": "Glycosylation may influence tissue-specific immune responses.", "mechanism": "Higher IgG concentration in patients with candidiasis at non-oral sites.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "Viral hepatitis (VH) with moderate/high ALT/AST", "glycan_involvement": "IgM glycosylation may affect immune activation in hepatitis.", "mechanism": "Higher IgM levels associated with increased liver enzyme activity in VH.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "medium", "disease": "Viral hepatitis (VH) with moderate/high ALT/AST", "glycan_involvement": "IgG glycosylation may modulate inflammation in hepatitis.", "mechanism": "Higher IgG levels associated with increased liver enzyme activity in VH.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "IgG glycosylation status may still influence disease progression.", "mechanism": "No significant difference in IgG levels across HIV-infected patient groups.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "Glycosylation may affect IgM function in HIV.", "mechanism": "IgM levels vary depending on coinfection status.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "IgA glycosylation impacts mucosal immunity in HIV.", "mechanism": "IgA levels vary with presence/absence of candidiasis.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC3360408" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus infection (HIV/AIDS)", "glycan_involvement": "Glycosylation affects gp140's conformation and epitope exposure, influencing antibody recognition.", "mechanism": "gp140 is a key immunogen for eliciting neutralizing antibody responses in HIV vaccine development.", "protein": "HIV-1 gp140", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3441591" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus infection (HIV/AIDS)", "glycan_involvement": "Dense glycan shield on gp120 impacts immunogenicity and antibody accessibility.", "mechanism": "gp120 is targeted by antibodies; its glycosylation shields epitopes and modulates immune response.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3441591" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation of the V1-V2 domain is critical for antibody recognition and protective immune response.", "mechanism": "Antibodies targeting the glycosylated V1-V2 domain, specifically the V2 loop (positions 165-178), are associated with reduced risk of HIV infection.", "protein": "gp120", "relationship_type": "protective", "source_pmcid": "PMC3441914" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Glycosylation is required for antibody binding and immune correlate analysis.", "mechanism": "Serum antibody reactivity to the glycosylated gp70-V1-V2 fusion protein correlates with lower risk of HIV infection.", "protein": "gp70-V1-V2 fusion protein", "relationship_type": "biomarker", "source_pmcid": "PMC3441914" }, { "confidence": "high", "disease": "Papillary thyroid carcinoma", "glycan_involvement": "Tg glycosylation affects its stability and secretion, impacting its utility as a biomarker.", "mechanism": "Elevated serum Tg indicates presence and burden of papillary thyroid carcinoma.", "protein": "Thyroglobulin (Tg)", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine resid", "gene_name": "TG", "glycan_count": 1, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G64527OM" ], "uniprot_id": "P01267" }, "relationship_type": "biomarker", "source_pmcid": "PMC3555358" }, { "confidence": "high", "disease": "Pulmonary metastases from papillary thyroid carcinoma", "glycan_involvement": "Glycosylation of Tg may influence its immunogenicity and detection in assays.", "mechanism": "High Tg levels correlate with metastatic disease, especially in diffuse pulmonary metastases.", "protein": "Thyroglobulin (Tg)", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine resid", "gene_name": "TG", "glycan_count": 1, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G64527OM" ], "uniprot_id": "P01267" }, "relationship_type": "biomarker", "source_pmcid": "PMC3555358" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "CHI3L1 is a glycoprotein; glycosylation may affect its stability and secretion in urine.", "mechanism": "Urinary CHI3L1 levels rise early after cardiac surgery in patients who develop AKI, preceding increases in serum creatinine.", "protein": "Chitinase 3-like 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC3642991" }, { "confidence": "high", "disease": "Japanese Encephalitis", "glycan_involvement": "Glycosylation of E protein affects antigenicity and immune evasion.", "mechanism": "Envelope glycoprotein E mediates viral entry and is targeted by neutralizing antibodies.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3650185" }, { "confidence": "high", "disease": "Japanese Encephalitis", "glycan_involvement": "Glycosylation is essential for NS1 secretion and stability.", "mechanism": "NS1 is secreted during infection and detectable in serum, serving as a diagnostic marker.", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC3650185" }, { "confidence": "high", "disease": "Classical Swine Fever", "glycan_involvement": "Glycosylation modulates E2 immunogenicity and receptor binding.", "mechanism": "E2 glycoprotein is the major immunogenic protein and target for vaccine development.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3650185" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation modulates VCAM-1 stability and cell adhesion.", "mechanism": "Resveratrol decreases VCAM-1 expression, reducing vascular inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects MMP-9 secretion and activity.", "mechanism": "Resveratrol suppresses MMP-9 mRNA, limiting extracellular matrix degradation.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "EGFR glycosylation regulates ligand binding and signaling.", "mechanism": "Polyphenols block EGFR tyrosine kinase activity, inhibiting tumor growth.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation is essential for CD36 membrane localization.", "mechanism": "Proanthocyanidins regulate CD36 expression, affecting oxLDL uptake.", "protein": "CD36", "protein_enriched": { "function": "Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipid", "gene_name": "CD36", "glycan_count": 42, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G04657PL", "G07246CJ", "G08146BT", "G20312EM", "G22310AV", "G23863VK", "G27058EU", "G41071NU", "G42962KI", "G44215PV", "G45495MK", "G51413EV", "G51640FO", "G57776ZS", "G62765YT", "G66163OV", "G70441OD", "G71146HJ", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83646BJ", "G84452RH", "G86795LJ", "G86880BF", "G90659AW", "G91636VS", "G49108TO", "G08290VR", "G15664MX", "G25079LO", "G29184RN", "G31852PQ", "G46503DX", "G63136LV", "G64527OM", "G66676MI", "G70101JE", "G02030ZB" ], "uniprot_id": "P16671" }, "relationship_type": "biomarker", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation stabilizes PON-1 in serum.", "mechanism": "Quercetin upregulates PON-1, enhancing HDL antioxidant function.", "protein": "PON-1", "relationship_type": "protective", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences transthyretin stability and amyloid binding.", "mechanism": "Resveratrol increases transthyretin secretion, preventing A\u03b2 aggregation.", "protein": "Transthyretin", "relationship_type": "protective", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects CYP1A1 localization and activity.", "mechanism": "Berry polyphenols inhibit CYP1A1, reducing carcinogen activation.", "protein": "CYP1A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "high", "disease": "Type II Diabetes", "glycan_involvement": "Glycosylation is required for \u03b1-glucosidase enzymatic activity.", "mechanism": "Anthocyanins and quercetin glycosides inhibit \u03b1-glucosidase, lowering postprandial glucose.", "protein": "\u03b1-glucosidase", "protein_enriched": { "function": "Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consis", "gene_name": "OPG099", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DOU2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Type II Diabetes", "glycan_involvement": "Glycosylation modulates GLUT2 trafficking and function.", "mechanism": "Quercetin inhibits GLUT2-mediated glucose uptake.", "protein": "GLUT2", "protein_enriched": { "function": "Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the ", "gene_name": "SLC2A2", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G43417UB" ], "uniprot_id": "P11168" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "medium", "disease": "Endometrial adenocarcinoma", "glycan_involvement": "Glycosylation impacts EST stability and substrate specificity.", "mechanism": "Quercetin and resveratrol inhibit EST activity, affecting estrogen metabolism.", "protein": "EST (Estrogen sulfotransferase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC3871896" }, { "confidence": "high", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "N-glycosylation critical for membrane localization and function.", "mechanism": "Regulates transport of antidepressants and antipsychotics across blood-brain barrier, affecting drug efficacy.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic target", "source_pmcid": "PMC4034064" }, { "confidence": "high", "disease": "Extrapyramidal Symptoms (EPS)", "glycan_involvement": "Glycosylation affects receptor folding and ligand binding.", "mechanism": "High occupancy by antipsychotics induces EPS in MDD/TRD treatment.", "protein": "Dopamine D2 receptor", "relationship_type": "causal", "source_pmcid": "PMC4034064" }, { "confidence": "high", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Glycosylation modulates receptor signaling and drug binding.", "mechanism": "Antagonism by atypical antipsychotics augments SSRI efficacy in TRD.", "protein": "Serotonin 5-HT2A receptor", "relationship_type": "therapeutic target", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Sleep Disturbance", "glycan_involvement": "Glycosylation influences receptor surface expression.", "mechanism": "Antagonism by quetiapine improves sleep in MDD/TRD.", "protein": "Histamine H1 receptor", "relationship_type": "therapeutic target", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Glycosylation required for transporter stability and activity.", "mechanism": "Blocked by norquetiapine, increasing norepinephrine and improving depressive symptoms.", "protein": "Norepinephrine transporter (NET)", "relationship_type": "therapeutic target", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Hyperprolactinemia", "glycan_involvement": "Glycosylation essential for hormone stability and secretion.", "mechanism": "Antipsychotics may elevate prolactin; aripiprazole does not worsen levels.", "protein": "Prolactin", "protein_enriched": { "function": "Prolactin acts primarily on the mammary gland by promoting lactation", "gene_name": "PRL", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01236" }, "relationship_type": "biomarker", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Agranulocytosis", "glycan_involvement": "Cell surface glycoproteins mediate immune recognition.", "mechanism": "Clozapine selectively affects these precursors, leading to agranulocytosis.", "protein": "Polymorphonuclear leukocyte precursor", "relationship_type": "causal", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "N-glycosylation modulates enzyme stability.", "mechanism": "Targeted by MAOI antidepressants; glycosylation affects enzyme activity.", "protein": "Monoamine oxidase A (MAOA)", "protein_enriched": { "function": "Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metaboli", "gene_name": "MAOA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P21397" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC4034064" }, { "confidence": "medium", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Indirectly affects glycoprotein function via methylation.", "mechanism": "Augments antidepressant response; involved in methylation of glycan biosynthesis.", "protein": "S-Adenosyl-L-methionine (SAMe)", "relationship_type": "therapeutic agent", "source_pmcid": "PMC4034064" }, { "confidence": "low", "disease": "Major Depressive Disorder (MDD)", "glycan_involvement": "Thyroid hormone receptors are glycosylated, affecting hormone binding.", "mechanism": "Augments antidepressant response via thyroid hormone receptor (glycoprotein).", "protein": "Triiodothyronine (T3)", "relationship_type": "therapeutic agent", "source_pmcid": "PMC4034064" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ApoE structure and receptor interactions.", "mechanism": "APOE-4 allele increases risk and worsens therapeutic response; influences amyloid and tau pathology.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycosylation modulates chaperone activity.", "mechanism": "CLU gene variants associated with AD risk; involved in amyloid clearance.", "protein": "Clusterin (CLU, ApoJ)", "relationship_type": "biomarker/susceptibility", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ligand binding and immune function.", "mechanism": "CR1 gene variants linked to AD risk; modulates immune response and amyloid clearance.", "protein": "Complement receptor 1 (CR1)", "protein_enriched": { "function": "Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). Mediates the bi", "gene_name": "CR1", "glycan_count": 13, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22310AV", "G40834TG", "G45395BF", "G47748JZ", "G48414YA", "G54285KU", "G57888GL", "G82830MN", "G06356OH", "G27058EU", "G79666IR", "G86795LJ", "G49108TO" ], "uniprot_id": "P17927" }, "relationship_type": "susceptibility", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for \u03b3-secretase activity and trafficking.", "mechanism": "NCSTN is part of \u03b3-secretase complex; overexpression increases A\u03b2 production.", "protein": "Nicastrin (NCSTN)", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates ligand binding and receptor signaling.", "mechanism": "RAGE mediates A\u03b2 transport and toxicity; gene variants increase AD risk.", "protein": "Receptor for Advanced Glycation End Products (RAGE)", "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC4034082" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects lipid binding and stability.", "mechanism": "ApoD levels increased in hippocampus and CSF of AD patients.", "protein": "Apolipoprotein D (ApoD)", "relationship_type": "biomarker", "source_pmcid": "PMC4034082" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Predicted glycosylation may affect channel function.", "mechanism": "CALHM1 P86L polymorphism associated with AD; regulates Ca2+ and A\u03b2 levels.", "protein": "CALHM1", "protein_enriched": { "function": "Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes (By similarity). With CALHM3 forms a fast-activating voltage-gated ATP-re", "gene_name": "CALHM1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8IU99" }, "relationship_type": "susceptibility", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation required for receptor function and APP interaction.", "mechanism": "SORLA regulates APP trafficking; underexpression leads to amyloid accumulation.", "protein": "SORLA (SORL1)", "relationship_type": "causal/protective", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation modulate APP processing and A\u03b2 generation.", "mechanism": "APP mutations cause familial AD; abnormal processing leads to A\u03b2 accumulation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect complex assembly and function.", "mechanism": "PSEN1 mutations alter \u03b3-secretase activity, increasing A\u03b2 production.", "protein": "Presenilin 1 (PSEN1)", "relationship_type": "causal", "source_pmcid": "PMC4034082" }, { "confidence": "high", "disease": "Prostate Cancer", "glycan_involvement": "Glycosylation affects PSMA localization and stability on cell surface.", "mechanism": "PSMA is overexpressed in prostate cancer cells and used for aptamer-mediated targeted drug delivery.", "protein": "Prostate Specific Membrane Antigen (PSMA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "high", "disease": "Leukemia (Acute Lymphoblastic)", "glycan_involvement": "Glycosylation may influence PTK7 cell surface expression.", "mechanism": "PTK7 is upregulated in leukemia cells and targeted by aptamers for selective drug delivery.", "protein": "Protein Tyrosine Kinase 7 (PTK7)", "protein_enriched": { "function": "Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Function", "gene_name": "PTK7", "glycan_count": 77, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G08918WF", "G11629QQ", "G15169WU", "G20312EM", "G27058EU", "G33567AB", "G33791AF", "G34617SM", "G34989PA", "G41071NU", "G43223CG", "G45395BF", "G47518TP", "G48414YA", "G50427EO", "G52890YB", "G57776ZS", "G62765YT", "G64394MX", "G64527OM", "G70101JE", "G70232NH", "G72291OX", "G75983OB", "G77582RK", "G79286RS", "G80920RR", "G81198YO", "G81263BG", "G82463GQ", "G83229XP", "G84452RH", "G84664JR", "G86795LJ", "G90382BL", "G94917XT", "G95133RI", "G22310AV", "G37881RL", "G40926MX", "G73291XG", "G49955PK", "G06110VR", "G20210JR", "G23294PN", "G36379GD", "G37399XV", "G92062TF", "G00912UN", "G04657PL", "G05933EN", "G14191MJ", "G25418HZ", "G25451PN", "G40834TG", "G44215PV", "G47012YE", "G47737VJ", "G60033FS", "G60177UT", "G70619PT", "G79666IR", "G80223IX", "G82830MN", "G83400DU", "G87051GH", "G57321FI", "G02815KT", "G28541PG", "G31852PQ", "G41247ZX", "G42124LM", "G65184UU", "G87389XI", "G49108TO" ], "uniprot_id": "Q13308" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "medium", "disease": "Cancer (general, e.g., HeLa, C6 glioma)", "glycan_involvement": "Glycosylation may modulate nucleolin's membrane localization.", "mechanism": "Nucleolin is highly expressed on cancer cell membranes and targeted by aptamers for imaging and drug delivery.", "protein": "Nucleolin", "protein_enriched": { "function": "Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding t", "gene_name": "NCL", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G18647XP", "G37399XV", "G41247ZX", "G68735SN" ], "uniprot_id": "P19338" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "high", "disease": "Epidermoid Carcinoma, Breast Cancer", "glycan_involvement": "N-glycosylation regulates EGFR ligand binding and dimerization.", "mechanism": "EGFR is overexpressed in various cancers and targeted by aptamer-functionalized nanoparticles.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "medium", "disease": "Lysosomal Storage Disease", "glycan_involvement": "Glycosylation is essential for transferrin receptor function and trafficking.", "mechanism": "Aptamer-mediated delivery of lysosomal enzymes via transferrin receptor corrects glycosaminoglycan degradation defects.", "protein": "Transferrin Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "medium", "disease": "Breast Cancer, Ovarian Cancer", "glycan_involvement": "O-glycosylation patterns are altered in cancer, affecting immune recognition.", "mechanism": "Mucin-1 is overexpressed and aberrantly glycosylated in cancer cells, targeted by aptamers for drug delivery.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation modulates tenascin-C interactions in the extracellular matrix.", "mechanism": "Tenascin-C is upregulated in glioblastoma and targeted by aptamers for imaging and potential therapy.", "protein": "Tenascin-C", "relationship_type": "biomarker", "source_pmcid": "PMC4058663" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune detection.", "mechanism": "gp120 is targeted by aptamers for selective delivery to HIV-infected cells.", "protein": "gp120 (HIV envelope glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "Glycosylation affects antibody stability and function.", "mechanism": "Used as a marker for B-cell lineage in leukemia, targeted by aptamers for cell identification.", "protein": "Immunoglobulin Heavy Mu Chain", "relationship_type": "biomarker", "source_pmcid": "PMC4058663" }, { "confidence": "low", "disease": "Cancer (drug delivery context)", "glycan_involvement": "Glycosylation may influence albumin's pharmacokinetics.", "mechanism": "Albumin-based nanoparticles are used for enhanced drug delivery to tumors.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC4058663" }, { "confidence": "high", "disease": "Esophageal carcinoma", "glycan_involvement": "CD34 is a heavily glycosylated sialomucin; glycosylation is essential for its function as a vascular marker.", "mechanism": "CD34 is highly expressed in the vasculature of the esophageal wall, including regions relevant to carcinoma progression.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC4070603" }, { "confidence": "medium", "disease": "Esophageal stricture", "glycan_involvement": "Cytokeratins are glycoproteins; glycosylation affects their structural and functional properties in epithelial repair.", "mechanism": "Cytokeratin pattern in fabricated epidermal cell sheets mimics native epidermis, supporting tissue repair and preventing stricture.", "protein": "Cytokeratin", "relationship_type": "biomarker", "source_pmcid": "PMC4070603" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Hyaluronate is a glycosaminoglycan; its viscoelastic properties depend on glycan structure.", "mechanism": "Used as a submucosal injection to facilitate endoscopic submucosal dissection (ESD) by creating a fluid cushion.", "protein": "Sodium hyaluronate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4070603" }, { "confidence": "medium", "disease": "Duodenal superficial neoplasm", "glycan_involvement": "Glycosylation (polymer length) determines its effectiveness as a cushion.", "mechanism": "Injected to improve safety and efficacy of ESD in duodenal neoplasms.", "protein": "Sodium hyaluronate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4070603" }, { "confidence": "medium", "disease": "Head and neck cancer", "glycan_involvement": "Glycosylation is critical for CD34's function as a vascular marker.", "mechanism": "CD34 marks vascular structures in tissues where superficial carcinomas are detected.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC4070603" }, { "confidence": "medium", "disease": "Esophageal carcinoma", "glycan_involvement": "Glycosylation modulates cytokeratin stability and function.", "mechanism": "Cytokeratin expression in cell sheets supports epithelial identity in tissue engineering for esophageal repair.", "protein": "Cytokeratin", "relationship_type": "biomarker", "source_pmcid": "PMC4070603" }, { "confidence": "medium", "disease": "Colorectal neoplasia", "glycan_involvement": "Glycosylation is essential for CD34's role in vascular endothelium.", "mechanism": "CD34 is used in histological analysis to identify vascularization in neoplastic lesions.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC4070603" }, { "confidence": "high", "disease": "Autoimmune diabetes", "glycan_involvement": "Glycoprotein acts as antigen; glycosylation may affect immunogenicity.", "mechanism": "Expression of LCMV glycoprotein in pancreatic beta cells triggers CD8+ T cell-mediated autoimmune diabetes upon LCMV infection.", "protein": "LCMV glycoprotein", "protein_enriched": { "function": "Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficie", "gene_name": "GPC", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P07399" }, "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "high", "disease": "Viral infection (VSV)", "glycan_involvement": "No direct glycan modification, but impacts glycoprotein-mediated immune responses.", "mechanism": "UBP43 inhibits IFN-I signaling in CD169+ macrophages, allowing enforced VSV replication and strong immune activation.", "protein": "UBP43 (USP18)", "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "medium", "disease": "Viral infection (VSV)", "glycan_involvement": "CD169 is a sialic acid-binding lectin; glycan recognition may mediate viral uptake.", "mechanism": "CD169+ macrophages selectively permit VSV replication, driving immune activation.", "protein": "CD169 (Siglec-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "medium", "disease": "Immunopathology during chronic virus infection", "glycan_involvement": "Glycosylation may modulate antigenicity and immune response.", "mechanism": "Viral glycoprotein expression leads to persistent immune activation and immunopathology.", "protein": "LCMV glycoprotein", "protein_enriched": { "function": "Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficie", "gene_name": "GPC", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P07399" }, "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "high", "disease": "Autoimmune diabetes", "glycan_involvement": "Indirect; facilitates glycoprotein antigen presentation.", "mechanism": "UBP43 expression in innate immune cells enables enforced viral replication, promoting autoimmune diabetes via immune activation.", "protein": "UBP43 (USP18)", "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "medium", "disease": "Viral infection (VSV)", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "VSV glycoprotein acts as antigen, driving adaptive immune activation.", "protein": "VSV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "medium", "disease": "Autoimmune diabetes", "glycan_involvement": "Glycan recognition by CD169 may mediate antigen uptake.", "mechanism": "CD169+ macrophages facilitate enforced viral replication, promoting autoimmune diabetes.", "protein": "CD169 (Siglec-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "low", "disease": "Transplantation complications", "glycan_involvement": "Indirect; impacts glycoprotein antigen presentation.", "mechanism": "UBP43-mediated immune activation may contribute to complications during transplantation.", "protein": "UBP43 (USP18)", "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "low", "disease": "Transplantation complications", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Viral glycoprotein-induced immune activation may exacerbate transplantation complications.", "protein": "LCMV glycoprotein", "protein_enriched": { "function": "Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficie", "gene_name": "GPC", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "P07399" }, "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "low", "disease": "Immunopathology during chronic virus infection", "glycan_involvement": "Glycosylation may affect chronic immune activation.", "mechanism": "Persistent VSV glycoprotein antigen exposure drives immunopathology.", "protein": "VSV glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC4118444" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes and mediate immune evasion.", "mechanism": "gp120 mediates HIV entry into host cells by binding to CD4 and co-receptors.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC4211091" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "CVN specifically recognizes high-mannose glycans on gp120.", "mechanism": "CVN binds to gp120 glycans, blocking HIV entry into host cells.", "protein": "Cyanovirin-N (CVN)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O57650" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC4211091" }, { "confidence": "high", "disease": "Congenital Disorders of Glycosylation (CDG)", "glycan_involvement": "Altered N-glycosylation (desialylation, fucosylation)", "mechanism": "Abnormal glycosylation pattern (loss of sialic acid, increased fucosylation) detected by mass spectrometry distinguishes CDG from secondary glycosylation defects.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC4212306" }, { "confidence": "high", "disease": "End-stage liver disease", "glycan_involvement": "Altered N-glycosylation", "mechanism": "Secondary abnormal glycosylation (increased fucosylation, loss of sialic acid) reflects impaired liver synthetic function.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation affects IgG immune complex formation and deposition", "mechanism": "IgG forms immune complexes with oxidative stress-derived antigens, contributing to hepatic inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Glycosylation of CD20 may affect B-cell function", "mechanism": "B-cell expansion and infiltration promote inflammation via interaction with T-cells and cytokine production.", "protein": "B220 (CD20)", "relationship_type": "causal", "source_pmcid": "PMC4212306" }, { "confidence": "high", "disease": "Schistosomal liver disease", "glycan_involvement": "Glycosaminoglycan accumulation in ECM", "mechanism": "Elevated serum hyaluronan reflects liver fibrosis severity in schistosomiasis.", "protein": "Hyaluronan (Hyaluronate)", "relationship_type": "biomarker", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Schistosomal liver disease", "glycan_involvement": "Glycosylation affects sCD14 stability and function", "mechanism": "Elevated sCD14 indicates inflammation and possible bacterial translocation in schistosomal portal hypertension.", "protein": "sCD14", "relationship_type": "biomarker", "source_pmcid": "PMC4212306" }, { "confidence": "high", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation may affect MMP-8 secretion and activity", "mechanism": "Systemic delivery of MMP-8 degrades collagen I, reduces fibrosis, and modulates fibrogenic gene expression.", "protein": "Matrix Metalloproteinase-8 (MMP-8)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Wilson disease-like phenotype", "glycan_involvement": "Altered glycosylation may affect ceruloplasmin stability", "mechanism": "Low ceruloplasmin levels associated with copper accumulation and abnormal glycosylation in Wilson-like disease.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation may affect CB1 receptor localization/function", "mechanism": "Gene silencing of CB1 reduces fibrogenic molecules and fibrosis in experimental models.", "protein": "CB1 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4212306" }, { "confidence": "medium", "disease": "Liver fibrosis/cirrhosis", "glycan_involvement": "Glycosylation affects PON-1 activity", "mechanism": "Melatonin increases PON-1 activity, improving oxidative stress and reducing fibrosis.", "protein": "Paraoxonase 1 (PON-1)", "relationship_type": "protective", "source_pmcid": "PMC4212306" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "Cell surface glycoproteins mediate immune compatibility and transfusion reactions.", "mechanism": "PRBC transfusion restores oxygen-carrying capacity in anemic patients.", "protein": "Packed Red Blood Cells (PRBC)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4455103" }, { "confidence": "high", "disease": "Hemorrhagic conditions", "glycan_involvement": "Platelet glycoproteins (e.g., GPIIb/IIIa) are critical for aggregation and immune recognition.", "mechanism": "Platelet transfusion treats bleeding due to thrombocytopenia.", "protein": "Platelets", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4455103" }, { "confidence": "high", "disease": "Coagulation disorders", "glycan_involvement": "Plasma glycoproteins (e.g., fibrinogen, clotting factors) require glycosylation for stability and function.", "mechanism": "FFP provides clotting factors to correct coagulopathies.", "protein": "Fresh Frozen Plasma (FFP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4455103" }, { "confidence": "high", "disease": "Coagulation disorders", "glycan_involvement": "Glycosylation of fibrinogen and factor VIII affects their activity and half-life.", "mechanism": "Cryoprecipitate supplies fibrinogen and factor VIII for bleeding disorders.", "protein": "Cryoprecipitate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4455103" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation required for secretion and function; binds chitin and glycan structures.", "mechanism": "Promotes airway inflammation and remodeling; levels correlate with severity and subepithelial thickness.", "protein": "YKL-40 (CHI3L1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation critical for oligomerization and pathogen binding.", "mechanism": "Elevated plasma levels in COPD; predicts exacerbation risk.", "protein": "SP-D", "relationship_type": "biomarker", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation affects stability and anti-inflammatory activity.", "mechanism": "Lower plasma levels in COPD; protects against smoke-induced inflammation.", "protein": "CC16", "relationship_type": "biomarker/protective", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation modulates ligand binding and decoy function.", "mechanism": "Reduced plasma levels in COPD; inversely related to emphysema severity.", "protein": "sRAGE", "relationship_type": "biomarker/protective", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation influences secretion and substrate specificity.", "mechanism": "Elevated in asthma; promotes airway inflammation resolution and subepithelial fibrosis.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD/Emphysema", "glycan_involvement": "Glycosylation affects enzyme activity and tissue localization.", "mechanism": "Promotes emphysema by degrading elastin and generating chemotactic fragments.", "protein": "MMP-12", "relationship_type": "causal", "source_pmcid": "PMC4595244" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation modulates cell surface expression and activity.", "mechanism": "Genetic variants linked to asthma and airway remodeling; may regulate angiogenesis.", "protein": "ADAM33", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC4595244" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation affects cell-cell interactions and protease activity.", "mechanism": "Regulates leukocyte apoptosis and migration; conflicting roles in inflammation.", "protein": "ADAM8", "protein_enriched": { "function": "Has anti-angiogenic properties", "gene_name": "ADAMTS8", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UP79" }, "relationship_type": "causal/protective", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "Glycosylation required for chemokine activity and receptor binding.", "mechanism": "Elevated plasma levels associated with reduced lung function, frequent exacerbations, and mortality.", "protein": "CCL18", "relationship_type": "biomarker", "source_pmcid": "PMC4595244" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation essential for secretion and clotting function.", "mechanism": "Elevated plasma levels predict exacerbation risk, exercise capacity, and mortality.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC4595244" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Altered glycosylation may affect protein stability and function in obesity.", "mechanism": "Serum total protein levels reflect metabolic status in obesity.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of apolipoproteins modulates HDL function.", "mechanism": "HDL levels are used to assess lipid profile disturbances in obesity.", "protein": "HDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects LDL receptor binding and clearance.", "mechanism": "LDL levels indicate risk for metabolic syndrome in obesity.", "protein": "LDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation of apolipoproteins influences VLDL metabolism.", "mechanism": "VLDL levels reflect triglyceride transport in metabolic disease.", "protein": "VLDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "ALT is a marker of liver function, often elevated in obesity.", "protein": "ALT (alanine transaminase)", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Minor glycosylation may affect enzyme stability.", "mechanism": "AST is a marker of liver and metabolic health.", "protein": "AST (aspartate transaminase)", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Kidney disease", "glycan_involvement": "Glycosylation status may change in renal disease.", "mechanism": "Serum protein levels can indicate renal function.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation modulates HDL anti-inflammatory properties.", "mechanism": "HDL is typically reduced in obesity.", "protein": "HDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation affects LDL atherogenicity.", "mechanism": "LDL is often elevated in obesity.", "protein": "LDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation affects VLDL secretion and clearance.", "mechanism": "VLDL is often elevated in obesity.", "protein": "VLDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653405" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects stability and function of serum proteins.", "mechanism": "Serum total protein levels are used to assess metabolic status in obesity.", "protein": "Total protein", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "HDL particles contain glycoproteins (e.g., ApoA-I) whose glycosylation modulates function.", "mechanism": "HDL levels reflect lipid metabolism disturbances in obesity.", "protein": "HDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "LDL contains glycoproteins (e.g., ApoB) with glycan modifications affecting clearance.", "mechanism": "LDL levels are elevated in metabolic syndrome and obesity.", "protein": "LDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "medium", "disease": "Dyslipidemia", "glycan_involvement": "VLDL glycoproteins are involved in lipid transport and metabolism.", "mechanism": "VLDL levels indicate altered triglyceride transport in obesity.", "protein": "VLDL cholesterol", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect enzyme stability and secretion.", "mechanism": "ALT elevation signals hepatic injury in metabolic disease.", "protein": "ALT (alanine aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "AST is released during liver cell damage in obesity.", "protein": "AST (aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC4653521" }, { "confidence": "high", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "IL28B is a glycoprotein; glycosylation may affect its stability and secretion, but specific glycan involvement not detailed.", "mechanism": "IL28B gene polymorphism rs8099917 TT genotype is associated with higher sustained virological response (SVR) to pegylated interferon/ribavirin therapy.", "protein": "Interleukin 28B (IL28B) / Interferon lambda 3 (IFNL3)", "relationship_type": "biomarker", "source_pmcid": "PMC4726832" }, { "confidence": "high", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "Glycosylation may influence IL28B function, but not specifically addressed.", "mechanism": "IL28B gene polymorphism rs8099917 G allele is a risk factor for failure of response to therapy.", "protein": "Interleukin 28B (IL28B) / Interferon lambda 3 (IFNL3)", "relationship_type": "biomarker", "source_pmcid": "PMC4726832" }, { "confidence": "medium", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "No specific glycan involvement described.", "mechanism": "IL28B gene polymorphism rs12980275 is not significantly associated with SVR in genotype 4 patients.", "protein": "Interleukin 28B (IL28B) / Interferon lambda 3 (IFNL3)", "relationship_type": "biomarker", "source_pmcid": "PMC4726832" }, { "confidence": "high", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "AFP is a glycoprotein; glycosylation affects its serum stability and detection.", "mechanism": "Higher serum AFP levels are associated with failure to achieve SVR.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC4726832" }, { "confidence": "medium", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "Glycosylation may affect cytokine activity, but not specifically discussed.", "mechanism": "TT genotype of rs8099917 confers a protective effect for spontaneous viral clearance.", "protein": "Interleukin 28B (IL28B) / Interferon lambda 3 (IFNL3)", "relationship_type": "protective", "source_pmcid": "PMC4726832" }, { "confidence": "medium", "disease": "Chronic Hepatitis C (HCV) Genotype 4 Infection", "glycan_involvement": "No specific glycan involvement described.", "mechanism": "Serum IL28B levels do not significantly differ between responders and non-responders.", "protein": "Interleukin 28B (IL28B) / Interferon lambda 3 (IFNL3)", "relationship_type": "biomarker", "source_pmcid": "PMC4726832" }, { "confidence": "medium", "disease": "Ischemic stroke", "glycan_involvement": "GPIIb/IIIa is a glycoprotein whose glycosylation is essential for its function in platelet adhesion.", "mechanism": "GPIIb/IIIa inhibitors used during thrombectomy to prevent platelet aggregation.", "protein": "GPIIb/IIIa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4784112" }, { "confidence": "medium", "disease": "Hemorrhagic transformation", "glycan_involvement": "Glycosylation of astrocyte membrane proteins is critical for maintaining blood-brain barrier integrity.", "mechanism": "Ischemia induces retraction of astrocyte foot processes, increasing blood-brain barrier permeability and risk of hemorrhage.", "protein": "Astrocyte foot process glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC4784112" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation is essential for CHI3L1 secretion and stability in urine.", "mechanism": "Urinary CHI3L1 levels rise in response to kidney injury, reflecting renal damage.", "protein": "Chitinase 3-like protein 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC4796151" }, { "confidence": "high", "disease": "Sepsis-associated AKI", "glycan_involvement": "Glycosylation may affect CHI3L1 detection and function as a biomarker.", "mechanism": "Urinary CHI3L1 is validated as an early marker of AKI in septic mice and humans.", "protein": "Chitinase 3-like protein 1 (CHI3L1)", "relationship_type": "biomarker", "source_pmcid": "PMC4796151" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "NGAL glycosylation influences its urinary stability and detection.", "mechanism": "UNGAL is released in urine during kidney injury, indicating tubular damage.", "protein": "Neutrophil gelatinase-associated lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC4796151" }, { "confidence": "high", "disease": "Acute Coronary Syndrome (ACS)", "glycan_involvement": "Glycosylation affects stability and clearance.", "mechanism": "Troponin T is released into blood during myocardial injury.", "protein": "Troponin T", "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Acute Coronary Syndrome (ACS)", "glycan_involvement": "Glycosylation may influence immunodetection.", "mechanism": "Troponin I is released during myocardial cell damage.", "protein": "Troponin I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "Elevated LDL promotes atherogenesis.", "protein": "Low Density Lipoprotein (LDL)", "relationship_type": "causal", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation affects HDL function and anti-inflammatory properties.", "mechanism": "HDL facilitates reverse cholesterol transport.", "protein": "High Density Lipoprotein (HDL)", "relationship_type": "protective", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation (not classical glycosylation) of hemoglobin.", "mechanism": "HbA1c reflects average blood glucose over prior 2-3 months.", "protein": "Glycated Hemoglobin (HbA1c)", "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Thyroid Disease", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "TSH levels indicate thyroid function.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "medium", "disease": "Liver Dysfunction (secondary to statin therapy)", "glycan_involvement": "Some forms are glycosylated, affecting stability.", "mechanism": "Elevated enzymes indicate hepatic injury.", "protein": "Liver Enzymes (ALT/AST)", "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "medium", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation affects half-life and function.", "mechanism": "Low albumin may indicate renal loss or inflammation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "medium", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Glycosylation modulates clotting activity.", "mechanism": "Elevated fibrinogen is a risk factor for thrombosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Dyslipidemia", "glycan_involvement": "Glycosylation affects LDL metabolism.", "mechanism": "High LDL is diagnostic and causal for dyslipidemia.", "protein": "Low Density Lipoprotein (LDL)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC4833805" }, { "confidence": "high", "disease": "Pleural Effusion (Cardiac/Non-cardiac)", "glycan_involvement": "N-glycosylation affects stability and detection in assays.", "mechanism": "Elevated NT-proBNP in plasma/pleural fluid differentiates cardiac from non-cardiac causes of effusion in cats.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "high", "disease": "Degenerative Mitral Valve Disease", "glycan_involvement": "Glycosylation may affect protein stability and trafficking.", "mechanism": "Downregulation in PBMCs reflects myocardial distress and impaired Ca2+ cycling.", "protein": "SERCA2\u03b1", "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "high", "disease": "Degenerative Mitral Valve Disease", "glycan_involvement": "Potential glycosylation modulates regulatory function.", "mechanism": "Decreased PLN expression in PBMCs correlates with myocardial dysfunction.", "protein": "Phospholamban (PLN)", "protein_enriched": { "function": "Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+) (PubMed:28890335). Binds preferentially to the ATP-boun", "gene_name": "PLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P26678" }, "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "N-glycosylation critical for secretion and function.", "mechanism": "Urinary clusterin levels increase in AKI; used for diagnosis.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "N-glycosylation affects renal clearance.", "mechanism": "Serum cystatin C evaluated as CKD marker in cats.", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "Glycosylation modulates inhibitory activity.", "mechanism": "Serum levels increase in dogs with SIRS/sepsis.", "protein": "Alpha 1-Proteinase Inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "high", "disease": "Bovine Respiratory Disease (BRD)", "glycan_involvement": "Glycosylation influences acute phase response.", "mechanism": "Elevated SAA used for diagnosis of BRD in cattle.", "protein": "Serum Amyloid A", "relationship_type": "biomarker", "source_pmcid": "PMC4895366" }, { "confidence": "high", "disease": "Bovine Respiratory Disease (BRD)", "glycan_involvement": "Glycosylation affects binding and clearance.", "mechanism": "Increased haptoglobin is a diagnostic marker for BRD.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. 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glycosylation may affect stability and secretion.", "mechanism": "Elevated periostin levels correlate with eosinophilic inflammation in nasal polyps.", "protein": "Periostin", "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "high", "disease": "Allergic Asthma", "glycan_involvement": "IgE glycosylation modulates receptor binding and immune activation.", "mechanism": "IgE mediates allergic responses; anti-IgE therapy reduces asthma symptoms.", "protein": "Immunoglobulin E (IgE)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC4896250" }, { "confidence": "high", "disease": "Hereditary Angioedema (C1-INH deficiency)", "glycan_involvement": "N-glycosylation required for C1-INH function and stability.", "mechanism": "Deficiency of glycosylated C1-INH leads to uncontrolled complement activation and angioedema.", "protein": "C1 Inhibitor (C1-INH)", "relationship_type": "causal", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Allergic Asthma", "glycan_involvement": "Glycosylation affects pentraxin 3 secretion and immune modulation.", "mechanism": "Elevated sputum pentraxin 3 levels are associated with asthma severity.", "protein": "Pentraxin 3", "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Chronic Spontaneous Urticaria", "glycan_involvement": "Clusterin glycosylation influences its chaperone activity.", "mechanism": "Clusterin levels, combined with autologous serum skin test, predict antihistamine-refractoriness.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Atopic Dermatitis", "glycan_involvement": "Glycosylation status affects filaggrin processing and skin barrier function.", "mechanism": "Maternal n-glycosylation changes and filaggrin loss in children are linked to atopic dermatitis.", "protein": "Filaggrin", "protein_enriched": { "function": "Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis", "gene_name": "FLG", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20930" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Food Allergy", "glycan_involvement": "Antigen 5 is glycosylated; glycan moieties may affect allergenicity.", "mechanism": "Specific IgE antibodies to antigen 5 indicate echinococcus-related food allergy.", "protein": "Antigen 5 (Echinococcus granulosus)", "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Anaphylaxis", "glycan_involvement": "IgG4 glycosylation modulates effector functions and immune complex formation.", "mechanism": "Non-IgE, but specific IgG4-mediated responses can cause anaphylaxis (e.g., ofloxacin-induced).", "protein": "Immunoglobulin G4 (IgG4)", "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "medium", "disease": "Eosinophilic Rhinosinusitis", "glycan_involvement": "TSLP is glycosylated; glycosylation may regulate receptor interaction.", "mechanism": "TSLP downregulates human \u03b2-defensin 2 via STAT3 pathway, affecting inflammation.", "protein": "TSLP", "protein_enriched": { "function": "Cytokine that induces the release of T-cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly a", "gene_name": "TSLP", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q969D9" }, "relationship_type": "therapeutic target", "source_pmcid": "PMC4896250" }, { "confidence": "low", "disease": "Aspirin-Exacerbated Respiratory Disease", "glycan_involvement": "CD19 is a glycoprotein; glycosylation affects cell surface expression.", "mechanism": "Altered levels of CD19+ cells observed in AERD; may reflect B cell activation.", "protein": "CD19", "protein_enriched": { "function": "Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B", "gene_name": "CD19", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P15391" }, "relationship_type": "biomarker", "source_pmcid": "PMC4896250" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Heavy N-glycosylation shields Env from immune recognition and modulates receptor binding.", "mechanism": "Env mediates viral entry via CD4 and CCR5 binding.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC4946638" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "N-glycosylation affects CD4 structure and HIV binding.", "mechanism": "CD4 is the primary receptor for HIV-1 entry.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC4946638" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Glycosylation modulates CCR5 surface expression and HIV tropism.", "mechanism": "CCR5\u039432 mutation confers resistance to HIV-1 infection.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "protective", "source_pmcid": "PMC4946638" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "N-glycosylation required for MHC-I surface expression.", "mechanism": "Downregulation by Nef impairs immune recognition of infected cells.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC4946638" }, { "confidence": "high", "disease": "HIV-1 infection", "glycan_involvement": "Modulates trafficking of glycoproteins (CD4, MHC-I).", "mechanism": "Nef downregulates CD4 and MHC-I, enhancing viral persistence.", "protein": "Nef", "protein_enriched": { "function": "Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host ", "gene_name": "nef", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03407" }, "relationship_type": "causal", "source_pmcid": "PMC4946638" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "Indirect; modulates viral DNA editing, not glycosylation.", "mechanism": "Upregulated in M1-polarized macrophages, restricts HIV replication.", "protein": "APOBEC3A", "protein_enriched": { "function": "DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retro", "gene_name": "APOBEC3C", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9NRW3" }, "relationship_type": "protective", "source_pmcid": "PMC4946638" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "Indirect; affects transcriptional silencing, not glycosylation.", "mechanism": "Suppresses Sp1-driven HIV transcription, promoting latency.", "protein": "TRIM22", "protein_enriched": { "function": "Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity (PubMed:25683609, PubMed:35777501). Restricts the replication of many viruses including HIV-1, encepha", "gene_name": "TRIM22", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8IYM9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC4946638" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "Potential O-glycosylation affects chromatin binding.", "mechanism": "Facilitates HIV integration into active chromatin, modulates latency.", "protein": "LEDGF/p75", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by ", "gene_name": "PRDX4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13162" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC4946638" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "Possible O-glycosylation modulates coactivator function.", "mechanism": "SRC-3 is essential for HIV transcriptional activation; pharmacological activation reactivates latent HIV.", "protein": "SRC-3 (Steroid receptor coactivator 3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4946638" }, { "confidence": "medium", "disease": "HIV latency", "glycan_involvement": "Glycosylation may affect receptor stability and chromatin recruitment.", "mechanism": "ESR-1 agonists suppress, antagonists promote HIV reactivation from latency.", "protein": "ESR-1 (Estrogen receptor alpha)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4946638" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "No direct glycosylation discussed in this article.", "mechanism": "Central to assembly, budding, and maturation of HIV virions; targeted by maturation inhibitors.", "protein": "HIV Gag polyprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC4975383" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "No direct glycosylation discussed in this article.", "mechanism": "High intra-patient genetic variability in p6 may influence viral maturation and response to therapy.", "protein": "p6 (Gag p6 domain)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC4975383" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation of Env is critical for immune evasion and infectivity.", "mechanism": "Mediates viral entry and fusion with host cells; glycosylation shields Env from immune recognition.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC5046194" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation required for BST-2 function and localization.", "mechanism": "Restricts HIV-1 release from infected cells; antagonized by HIV-1 Vpu and HIV-2 Env.", "protein": "BST-2/Tetherin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5046194" }, { "confidence": "high", "disease": "Retrovirus infection (general)", "glycan_involvement": "Binds sialic acid-containing glycans on viral particles.", "mechanism": "Mediates trans-infection of permissive lymphocytes by capturing sialylated viral particles.", "protein": "CD169 (Siglec-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC5046194" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates IFITM3 antiviral specificity and regulation.", "mechanism": "Restricts HIV-1 protein synthesis and viral entry.", "protein": "IFITM3", "protein_enriched": { "function": "Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating lig", "gene_name": "HGF", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P14210" }, "relationship_type": "protective", "source_pmcid": "PMC5046194" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Recognition of glycosylated stress ligands on infected cells.", "mechanism": "Mediates clearance of reactivated viral reservoirs by NK cells.", "protein": "NKG2D", "protein_enriched": { "function": "Involved in pre-mRNA splicing process (PubMed:11991638, PubMed:12084575, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre", "gene_name": "CRNKL1", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G10488MI", "G49108TO" ], "uniprot_id": "Q9BZJ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC5046194" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Env glycosylation required for BST-2 antagonism.", "mechanism": "Antagonizes BST-2/tetherin to promote viral release.", "protein": "HIV-2 Envelope glycoprotein (Env)", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P03375" }, "relationship_type": "causal", "source_pmcid": "PMC5046194" }, { "confidence": "medium", "disease": "Cancer (seminoma, melanoma)", "glycan_involvement": "Glycosylation may affect immunogenicity and cell interactions.", "mechanism": "Overexpression associated with cancer stem cell markers and malignancy.", "protein": "Human endogenous retrovirus type K (ERVK) Env", "relationship_type": "biomarker", "source_pmcid": "PMC5046194" }, { "confidence": "medium", "disease": "Human T cell leukemia virus type 1 (HTLV-1) infection", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Targeted by HTLV-1 Tax protein, may facilitate virus transmission.", "protein": "COL4A1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5046194" }, { "confidence": "medium", "disease": "Human T cell leukemia virus type 1 (HTLV-1) infection", "glycan_involvement": "Glycosylation affects extracellular matrix interactions.", "mechanism": "Targeted by HTLV-1 Tax protein, may facilitate virus transmission.", "protein": "COL4A2", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A2", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G57321FI", "G30221QT", "G59324HL", "G29068FM", "G43417UB" ], "uniprot_id": "P08572" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC5046194" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Highly glycosylated; glycans modulate immune recognition and receptor binding.", "mechanism": "Soluble gp120 enhances and neutralizes HIV-1 infection, influences selection of R5-tropic strains.", "protein": "gp120 (soluble)", "relationship_type": "causal", "source_pmcid": "PMC5046194" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Hemagglutinin is a glycoprotein; glycosylation is essential for its function and immune evasion.", "mechanism": "Hemagglutinin mediates viral entry into host cells.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC5054516" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HB36.6 targets the glycosylated hemagglutinin stalk region.", "mechanism": "HB36.6 binds the hemagglutinin stalk, neutralizing a broad range of influenza viruses.", "protein": "HB36.6", "relationship_type": "protective", "source_pmcid": "PMC5054516" }, { "confidence": "medium", "disease": "Cytokine storm (associated with influenza)", "glycan_involvement": "Glycosylation of hemagglutinin may modulate immune recognition.", "mechanism": "Hemagglutinin-mediated infection can trigger excessive immune response.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC5054516" }, { "confidence": "medium", "disease": "Cytokine storm (associated with influenza)", "glycan_involvement": "Acts via binding to glycosylated hemagglutinin.", "mechanism": "HB36.6 suppresses cytokine storm by reducing viral burden.", "protein": "HB36.6", "relationship_type": "protective", "source_pmcid": "PMC5054516" }, { "confidence": "medium", "disease": "Glomerulosclerosis (GS)", "glycan_involvement": "Glycosylation increases matrix deposition and sclerosis.", "mechanism": "PAS stain highlights glycoprotein accumulation in glomeruli, indicating sclerosis.", "protein": "PAS-positive glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC5064671" }, { "confidence": "medium", "disease": "Arteriolar hyalinosis (AH)", "glycan_involvement": "Glycosylated proteins contribute to hyaline formation.", "mechanism": "PAS stain detects glycoprotein-rich hyaline deposits in arterioles.", "protein": "PAS-positive glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC5064671" }, { "confidence": "medium", "disease": "Interstitial fibrosis/tubular atrophy (IF/TA)", "glycan_involvement": "Glycosylation promotes extracellular matrix expansion.", "mechanism": "PAS stain marks glycoprotein accumulation in interstitial matrix and tubules.", "protein": "PAS-positive glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC5064671" }, { "confidence": "low", "disease": "Renal function decline", "glycan_involvement": "Altered glycosylation correlates with tissue damage.", "mechanism": "PAS-positive changes in non-tumor parenchyma reflect underlying pathology linked to function loss.", "protein": "PAS-positive glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC5064671" }, { "confidence": "medium", "disease": "Diabetes Mellitus (DM)", "glycan_involvement": "Hyperglycemia drives abnormal glycosylation and matrix accumulation.", "mechanism": "Diabetes is associated with increased PAS-positive changes (GS, AH, IF/TA) in kidney.", "protein": "PAS-positive glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC5064671" }, { "confidence": "high", "disease": "Felis catus gammaherpesvirus 1 infection", "glycan_involvement": "Glycosylation required for viral entry and immune evasion", "mechanism": "Viral glycoprotein B gene used for qPCR detection of infection", "protein": "Glycoprotein B (FcaGHV1)", "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "high", "disease": "Leptospirosis", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition", "mechanism": "LipL32 gene detected by PCR as marker of pathogenic Leptospira in urine", "protein": "LipL32", "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Glycosylation modulates transporter function and localization", "mechanism": "Altered expression in intestinal epithelium and lamina propria in cats with IBD and alimentary lymphoma", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Immune-mediated disorders", "glycan_involvement": "Glycosylation affects IgA stability and mucosal immunity", "mechanism": "Altered IgA levels in Nova Scotia duck tolling retrievers with immune-mediated disorders", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "high", "disease": "Canine idiopathic pulmonary fibrosis", "glycan_involvement": "Glycosylation required for CRP secretion and function", "mechanism": "CRP used as acute phase marker in assessment of treatment response in dogs with bacterial pneumonia and pulmonary fibrosis", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may affect enzyme activity", "mechanism": "Transglutaminase 2 implicated in fibrosis after renal ischemia, relevant for feline CKD", "protein": "Transglutaminase 2", "relationship_type": "biomarker/causal", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation required for enzyme stability and activity", "mechanism": "Urinary alkaline phosphatase used for early recognition of AKI in dogs", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Inflammatory bowel disease (IBD)", "glycan_involvement": "Glycosylation may regulate enzyme localization", "mechanism": "COX2 expression increased in small intestinal epithelium of cats with IBD and lymphoma", "protein": "Cyclooxygenase 2 (COX2)", "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Glycosylation affects chemokine secretion and receptor binding", "mechanism": "CCL28 expression in colonic mucosa and mucus correlates with clinical and endoscopic activity in canine lymphocytic-plasmacytic colitis", "protein": "CCL28", "protein_enriched": { "function": "Chemotactic activity for resting CD4, CD8 T-cells and eosinophils. Binds to CCR3 and CCR10 and induces calcium mobilization in a dose-dependent manner", "gene_name": "CCL28", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NRJ3" }, "relationship_type": "biomarker", "source_pmcid": "PMC5259643" }, { "confidence": "high", "disease": "Bloody diarrhea", "glycan_involvement": "Toxins may target glycosylated host receptors", "mechanism": "NetE and NetF toxin genes associated with acute hemorrhagic and necrotizing gastroenteritis in dogs", "protein": "NetE/NetF toxins (C. perfringens)", "relationship_type": "causal", "source_pmcid": "PMC5259643" }, { "confidence": "high", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "N-glycosylation affects NT-proBNP stability and detection.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and is associated with CHF severity and prognosis in cats.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Myxomatous Mitral Valve Disease (MMVD)", "glycan_involvement": "Corin glycosylation affects its activity and localization.", "mechanism": "Corin converts pro-natriuretic peptides to active forms; altered corin expression/activity may contribute to MMVD progression and CHF.", "protein": "Corin", "protein_enriched": { "function": "Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing (PubMed:10880574, PubMed:20489134, PubMed:21288900, PubMed:21763278). Converts t", "gene_name": "CORIN", "glycan_count": 1, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y5Q5" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "T-cell Lymphocytic Gastrointestinal Lymphoma", "glycan_involvement": "Glycosylation modulates ABCB1 trafficking and function.", "mechanism": "P glycoprotein expression in feline lymphoma may mediate drug resistance.", "protein": "P glycoprotein (ABCB1)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Cardiac Disease", "glycan_involvement": "Glycosylation is essential for inhibitor stability and function.", "mechanism": "Fecal \u03b11-proteinase inhibitor concentrations are altered in dogs with cardiac disease.", "protein": "\u03b11-Proteinase Inhibitor", "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "N-glycosylation required for FGF-23 secretion and activity.", "mechanism": "FGF-23 levels are elevated in dogs with CKD and may predict disease progression.", "protein": "FGF-23", "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Obesity-related Cardiac Dysfunction", "glycan_involvement": "Glycosylation affects cytokine stability and receptor binding.", "mechanism": "Elevated GM-CSF in obese dogs indicates inflammation linked to cardiac dysfunction.", "protein": "GM-CSF", "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation required for multimerization and bioactivity.", "mechanism": "Adiponectin levels are associated with insulin sensitivity in dogs with diabetes.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Obesity-related Cardiac Dysfunction", "glycan_involvement": "Glycosylation modulates chemokine secretion and activity.", "mechanism": "KC-like chemokine is elevated in obese dogs, indicating inflammation.", "protein": "KC-like (CXCL1)", "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "Renal Dysfunction", "glycan_involvement": "Glycosylation affects NGAL stability and renal excretion.", "mechanism": "Urinary NGAL is used to monitor renal injury during diuretic therapy.", "protein": "NGAL (LCN2)", "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "low", "disease": "Gastrointestinal Motility Disorders", "glycan_involvement": "Glycosylation required for hormone stability.", "mechanism": "Plasma motilin levels are measured to assess GI motility in dogs.", "protein": "Motilin", "protein_enriched": { "function": "Plays an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle", "gene_name": "MLN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P12872" }, "relationship_type": "biomarker", "source_pmcid": "PMC5260423" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Albumin glycosylation may affect stability and function, but not directly discussed.", "mechanism": "Serum albumin levels correlate with advanced illness in HIV+ patients.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation status not specified.", "mechanism": "Albumin association with body composition measures in HIV+ but not HIV- women.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation critical for selectin function and ligand binding.", "mechanism": "Elevated sE-Selectin levels are markers of endothelial dysfunction in metabolic syndrome.", "protein": "sE-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "Increased tPAI-1 levels indicate pro-thrombotic state in metabolic syndrome.", "protein": "tPAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "high", "disease": "Metabolic syndrome", "glycan_involvement": "N-glycosylation required for ICAM-1 function.", "mechanism": "Elevated s-ICAM levels reflect inflammation and vascular risk in metabolic syndrome.", "protein": "s-ICAM", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "medium", "disease": "Lung function decline/obstructive lung disease", "glycan_involvement": "Glycosylation mediates selectin interactions in inflammation.", "mechanism": "Higher sE-Selectin levels associated with accelerated lung function decline post-exposure.", "protein": "sE-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "medium", "disease": "Lung function decline/obstructive lung disease", "glycan_involvement": "Glycosylation modulates inhibitor activity.", "mechanism": "Elevated tPAI-1 linked to impaired fibrinolysis and lung injury.", "protein": "tPAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "medium", "disease": "Lung function decline/obstructive lung disease", "glycan_involvement": "N-glycosylation essential for ICAM-1 function.", "mechanism": "Higher s-ICAM levels indicate increased inflammation and risk of lung obstruction.", "protein": "s-ICAM", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for selectin-mediated cell adhesion.", "mechanism": "Obesity is associated with increased sE-Selectin, reflecting endothelial activation.", "protein": "sE-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects tPAI-1 stability and function.", "mechanism": "Obesity increases tPAI-1, contributing to pro-thrombotic risk.", "protein": "tPAI-1", "relationship_type": "biomarker", "source_pmcid": "PMC5439735" }, { "confidence": "high", "disease": "Metastatic carcinoma", "glycan_involvement": "IL-2 is a glycoprotein; glycosylation may affect stability and immune recognition.", "mechanism": "IL-2 delivered via sterically stabilized liposomes increases leukocyte number and anti-tumor activity, improving survival in mice with metastatic carcinoma.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "PEGylation may mask glycan epitopes, altering immune response.", "mechanism": "PEGylated IL-2 administration causes marked toxicity, including severe thrombocytopenia.", "protein": "Interleukin-2 (IL-2)", "protein_enriched": { "function": "Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and toler", "gene_name": "IL2", "glycan_count": 20, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G65562ZE", "G74722FL", "G81006GJ", "G02561FC", "G10374FO", "G14227RA", "G18220BL", "G22140GZ", "G23863VK", "G37969WK", "G39943KJ", "G46687AB", "G49874UX", "G50045TK", "G57321FI", "G81295CK", "G97037FD" ], "uniprot_id": "P60568" }, "relationship_type": "causal (side effect)", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Diabetes (VP-deficiency)", "glycan_involvement": "VP is a peptide; not glycosylated, but carrier glycosylation may affect delivery.", "mechanism": "Liposome-encapsulated VP prolongs antidiuretic activity in VP-deficient rats.", "protein": "Arg8-vasopressin (VP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "high", "disease": "Vesicular stomatitis virus infection", "glycan_involvement": "Interferon-\u03b1 glycosylation affects stability and bioactivity.", "mechanism": "SLN-encapsulated interferon-\u03b1 shows antiviral activity and controlled release in vitro.", "protein": "Recombinant human interferon-\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Visceral leishmaniasis (vaccine context)", "glycan_involvement": "Lysozyme glycosylation may affect immunogenicity.", "mechanism": "SLN-encapsulated lysozyme retains activity, suitable for antigen delivery in vaccines.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "protective (vaccine antigen)", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Osteoporosis (implied)", "glycan_involvement": "sCT is a peptide; not glycosylated, but carrier glycosylation may affect mucosal uptake.", "mechanism": "Chitosan-coated SLNs provide sustained oral delivery of sCT, a peptide hormone for calcium regulation.", "protein": "Salmon calcitonin (sCT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "high", "disease": "Tetanus", "glycan_involvement": "Tetanus toxoid glycosylation may affect antigenicity and uptake.", "mechanism": "PLA-PEG nanoparticles enhance transmucosal delivery and absorption of tetanus toxoid.", "protein": "Tetanus toxoid", "protein_enriched": { "function": "Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can mov", "gene_name": "tetX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04958" }, "relationship_type": "protective (vaccine antigen)", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Inflammation (oxidative stress context)", "glycan_involvement": "Catalase glycosylation affects stability and activity.", "mechanism": "PEG-PLGA nanoparticles encapsulate catalase, protecting it from protease degradation for antioxidant therapy.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Bak glycosylation may affect cellular uptake and function.", "mechanism": "Liposome-conjugated Bak protein delivered to cancer cells induces apoptosis.", "protein": "Bak", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5445892" }, { "confidence": "medium", "disease": "Trypanosoma brucei infection (CNS)", "glycan_involvement": "Apolipoprotein glycosylation mediates interaction with endothelial cells.", "mechanism": "SLN surface adsorption of apolipoproteins enables crossing of the blood-brain barrier for CNS drug delivery.", "protein": "Apolipoproteins", "relationship_type": "protective (drug delivery facilitator)", "source_pmcid": "PMC5445892" }, { "confidence": "high", "disease": "Hepatic tumors", "glycan_involvement": "AFP is a glycoprotein; its glycosylation is essential for stability and detection in immunoassays.", "mechanism": "AFP levels in serum are elevated in patients with hepatic tumors, serving as a diagnostic marker.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC5449047" }, { "confidence": "high", "disease": "Yolk sac tumors", "glycan_involvement": "Glycosylation of AFP affects its immunoreactivity and detection sensitivity.", "mechanism": "AFP is secreted by yolk sac tumors, making it a useful marker for diagnosis and monitoring.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC5449047" }, { "confidence": "high", "disease": "Goldbloom syndrome (Transient periosteal hyperostosis with dysproteinemia)", "glycan_involvement": "Glycosylation affects globulin stability and serum levels during inflammation.", "mechanism": "Elevated alpha-1 globulin levels are associated with inflammatory episodes and dysproteinemia in Goldbloom syndrome.", "protein": "Alpha-1 globulin", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "high", "disease": "Goldbloom syndrome (Transient periosteal hyperostosis with dysproteinemia)", "glycan_involvement": "Glycosylation modulates globulin function and inflammatory response.", "mechanism": "Elevated alpha-2 globulin is part of the characteristic dysproteinemia in Goldbloom syndrome.", "protein": "Alpha-2 globulin", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "high", "disease": "Goldbloom syndrome (Transient periosteal hyperostosis with dysproteinemia)", "glycan_involvement": "IgG glycosylation influences immune effector functions.", "mechanism": "Increased gamma globulin (immunoglobulins) reflects immune activation in Goldbloom syndrome.", "protein": "Gamma globulin", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "high", "disease": "Goldbloom syndrome (Transient periosteal hyperostosis with dysproteinemia)", "glycan_involvement": "Minor glycosylation; not central to mechanism.", "mechanism": "Hypoalbuminemia is a marker of dysproteinemia and inflammation in Goldbloom syndrome.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "high", "disease": "Sj\u00f6gren\u2019s syndrome", "glycan_involvement": "Autoantibody glycosylation may affect antigen binding and pathogenicity.", "mechanism": "Presence of anti-Ro antibodies is associated with development and progression of Sj\u00f6gren\u2019s syndrome.", "protein": "Anti-Ro (SSA) antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC5461520" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate autoantibody effector functions.", "mechanism": "Anti-Ro antibodies are present in a subset of SLE patients and may predict specific clinical features.", "protein": "Anti-Ro (SSA) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "medium", "disease": "Mixed connective tissue disease (MCTD)", "glycan_involvement": "Glycosylation may influence autoantibody pathogenicity.", "mechanism": "Anti-Ro antibodies are present in some MCTD patients, indicating overlap with other autoimmune syndromes.", "protein": "Anti-Ro (SSA) antibody", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "high", "disease": "Acute rheumatic fever", "glycan_involvement": "IgG glycosylation modulates antibody effector functions and inflammation.", "mechanism": "Elevated anti-streptolysin O and anti-DNase B IgG antibodies indicate recent streptococcal infection and immune activation in acute rheumatic fever.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "medium", "disease": "Sj\u00f6gren\u2019s syndrome", "glycan_involvement": "Glycosylation may affect antibody clearance and immune modulation.", "mechanism": "Immunosuppressant treatment in children with anti-Ro antibodies may prevent progression to Sj\u00f6gren\u2019s syndrome.", "protein": "Anti-Ro (SSA) antibody", "relationship_type": "therapeutic_target/protective", "source_pmcid": "PMC5461520" }, { "confidence": "medium", "disease": "Acute rheumatic fever", "glycan_involvement": "IgG glycosylation influences inflammation and immune response.", "mechanism": "Elevated gamma globulin levels reflect immune activation in acute rheumatic fever.", "protein": "Gamma globulin", "relationship_type": "biomarker", "source_pmcid": "PMC5461520" }, { "confidence": "medium", "disease": "Aortic Thromboembolism (ATE)", "glycan_involvement": "Thrombomodulin is a glycoprotein; glycosylation is essential for its anticoagulant function.", "mechanism": "Down-regulation of thrombomodulin in left atrial endothelium is associated with a procoagulable state in cats with ATE.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "medium", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "Glycosylation modulates thrombomodulin stability and function.", "mechanism": "Reduced thrombomodulin expression in left atrium may contribute to prothrombotic risk in CHF.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "high", "disease": "Degenerative Mitral Valve Disease (DMVD)", "glycan_involvement": "Alpha-catenin is a glycoprotein; glycosylation may affect adherens junction stability.", "mechanism": "Decreased alpha-catenin levels in mitral valves are associated with DMVD in small breed dogs.", "protein": "Alpha-catenin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "medium", "disease": "Degenerative Mitral Valve Disease (DMVD)", "glycan_involvement": "Beta-catenin is glycosylated; glycan status may influence signaling.", "mechanism": "Decreased phosphorylated beta-catenin (P-Y142) in DMVD valves suggests altered Wnt signaling and cell adhesion.", "protein": "Beta-catenin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy (HCM) with Atrial Thrombosis (AT)", "glycan_involvement": "MMP-2 is a glycoprotein; glycosylation affects secretion and activity.", "mechanism": "Lower ventricular MMP-2 transcription in cats with HCM and AT suggests altered extracellular matrix remodeling.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy (HCM) with Atrial Thrombosis (AT)", "glycan_involvement": "TIMP-2 is glycosylated; glycosylation modulates inhibitor function.", "mechanism": "Lower ventricular TIMP-2 transcription in HCM+AT cats is linked to increased hypertrophy and fibrosis.", "protein": "TIMP-2", "protein_enriched": { "function": "Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10", "gene_name": "TIMP2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P16035" }, "relationship_type": "biomarker", "source_pmcid": "PMC5508335" }, { "confidence": "high", "disease": "Beh\u00e7et\u2019s disease", "glycan_involvement": "HLA-B51 is a glycoprotein; glycosylation affects antigen presentation", "mechanism": "Genetic association with increased risk and severity of Beh\u00e7et\u2019s disease", "protein": "HLA-B51", "relationship_type": "biomarker", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "AA amyloidosis", "glycan_involvement": "SAA is glycosylated; glycosylation may affect amyloidogenicity", "mechanism": "SAA is the precursor protein for amyloid A fibril deposition in organs", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "causal", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "Henoch-Sch\u00f6nlein purpura (HSP)", "glycan_involvement": "Aberrant glycosylation of IgA is implicated in pathogenesis", "mechanism": "IgA immune complex deposition in small vessels causes vasculitis", "protein": "IgA", "relationship_type": "causal/biomarker", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "\u03b22 glycoprotein I is glycosylated; glycan structure may affect antigenicity", "mechanism": "Autoantibodies against \u03b22 glycoprotein I promote thrombosis", "protein": "Antiphospholipid antibodies (anti-\u03b22 glycoprotein I)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC5592437" }, { "confidence": "medium", "disease": "FMF, HIDS/MKD, TRAPS", "glycan_involvement": "CRP is glycosylated; glycosylation may modulate function", "mechanism": "CRP is an acute phase reactant elevated during inflammation", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "FMF, SJIA, TRAPS, HIDS/MKD", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation may affect secretion/activity", "mechanism": "IL-1\u03b2 drives inflammation; targeted by canakinumab and anakinra", "protein": "IL-1\u03b2", "protein_enriched": { "function": "Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil ", "gene_name": "IL1B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01584" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC5592437" }, { "confidence": "medium", "disease": "CAPS (CINCA syndrome)", "glycan_involvement": "IL1RA is glycosylated; glycosylation may affect stability", "mechanism": "IL1RA inhibits IL-1\u03b2 signaling; decreased in CAPS, contributing to inflammation", "protein": "IL1RA", "relationship_type": "protective", "source_pmcid": "PMC5592437" }, { "confidence": "medium", "disease": "EGPA", "glycan_involvement": "MPO is a glycoprotein; glycosylation may affect antigenicity", "mechanism": "Anti-MPO antibodies are associated with vasculitic manifestations in EGPA", "protein": "Anti-MPO antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC5592437" }, { "confidence": "medium", "disease": "EGPA", "glycan_involvement": "IgE is glycosylated; glycosylation affects receptor binding", "mechanism": "Elevated IgE is characteristic of EGPA and reflects Th2/eosinophilic inflammation", "protein": "IgE", "relationship_type": "biomarker", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "APS, HSP with renal involvement", "glycan_involvement": "Glycosylation of \u03b22GPI influences antibody binding and pathogenicity", "mechanism": "Target of antiphospholipid antibodies, promoting thrombosis and renal pathology", "protein": "\u03b22 glycoprotein I", "relationship_type": "causal/biomarker", "source_pmcid": "PMC5592437" }, { "confidence": "high", "disease": "Heart disease (canine)", "glycan_involvement": "Glycosylation affects NT-proBNP stability and clearance.", "mechanism": "Elevated NT-proBNP reflects cardiac stress and dysfunction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Heart disease (canine)", "glycan_involvement": "Glycosylation may influence cTnI immunoreactivity.", "mechanism": "Increased cTnI indicates myocardial injury.", "protein": "cTnI", "relationship_type": "biomarker", "source_pmcid": "PMC5598894" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Clusterin is heavily glycosylated, affecting its renal filtration.", "mechanism": "Urinary clusterin increases with CKD severity.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC5598894" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation modulates cystatin B stability and excretion.", "mechanism": "Urinary cystatin B is elevated in CKD.", "protein": "Cystatin B", "protein_enriched": { "function": "This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B", "gene_name": "CSTB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04080" }, "relationship_type": "biomarker", "source_pmcid": "PMC5598894" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "NGAL glycosylation affects its renal handling.", "mechanism": "Urinary NGAL increases with renal injury.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Gangliosidoses (GM2)", "glycan_involvement": "Hex is a glycoprotein; glycosylation required for lysosomal targeting.", "mechanism": "Hex deficiency leads to GM2 ganglioside accumulation and neurodegeneration.", "protein": "Hexosaminidase (Hex)", "relationship_type": "causal", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Gangliosidoses (GM2)", "glycan_involvement": "Glycosylation required for function and stability.", "mechanism": "Deficiency impairs GM2 ganglioside degradation.", "protein": "GM2 activator protein", "protein_enriched": { "function": "The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and ", "gene_name": "GM2A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17900" }, "relationship_type": "causal", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Gangliosidoses (GM1)", "glycan_involvement": "Glycosylation required for lysosomal localization.", "mechanism": "\u03b2-gal deficiency causes GM1 ganglioside accumulation.", "protein": "\u03b2-galactosidase (\u03b2-gal)", "relationship_type": "causal", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Niemann-Pick type C (NPC)", "glycan_involvement": "NPC1 is a glycoprotein; glycosylation affects trafficking and function.", "mechanism": "NPC1 deficiency leads to lysosomal cholesterol and sphingolipid accumulation.", "protein": "NPC1", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, PubMed:1255468", "gene_name": "NPC1", "glycan_count": 34, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G46503DX", "G65184UU", "G65953PF", "G80920RR", "G83646BJ", "G87661QW", "G98611JV", "G85101WV", "G26436YP", "G28465XX", "G49108TO", "G00912UN", "G07246CJ", "G09831WQ", "G10486CT", "G20425TQ", "G27058EU", "G31852PQ", "G46902YN", "G59626AS", "G62765YT", "G90659AW", "G96368MM", "G05724UK", "G74381CZ", "G88520YF", "G22573RC", "G22768VO", "G37818NZ", "G40926MX", "G57776ZU", "G27947YN", "G45789UC", "G57489SP" ], "uniprot_id": "O15118" }, "relationship_type": "causal", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Niemann-Pick type C (NPC)", "glycan_involvement": "NPC2 glycosylation is essential for stability and function.", "mechanism": "NPC2 deficiency impairs cholesterol egress from lysosomes.", "protein": "NPC2", "protein_enriched": { "function": "Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:11125141, PubMed:15937921, PubMed:", "gene_name": "NPC2", "glycan_count": 32, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G28681TP", "G41247ZX", "G05049YU", "G06110VR", "G07810QS", "G14669DU", "G18647XP", "G23719VF", "G27915IV", "G31852PQ", "G34989PA", "G37818NZ", "G37995HC", "G43223CG", "G43734MM", "G45504EY", "G46691LC", "G54010QB", "G57317CE", "G57776ZS", "G62765YT", "G65344XH", "G69521XL", "G73027HY", "G80920RR", "G85282JO", "G87661QW", "G89045VA", "G90659AW", "G92050GC", "G49108TO" ], "uniprot_id": "P61916" }, "relationship_type": "causal", "source_pmcid": "PMC5598894" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "N-glycosylation affects antigenicity and immune recognition.", "mechanism": "HBsAg is used to diagnose and monitor HBV infection.", "protein": "Hepatitis B virus surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "N-glycosylation modulates secretion and immune evasion.", "mechanism": "HBeAg positivity indicates active viral replication.", "protein": "Hepatitis B virus e antigen (HBeAg)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Glycosylation may affect RT folding and function.", "mechanism": "RT is targeted by antiviral drugs; mutations confer drug resistance.", "protein": "Hepatitis B virus reverse transcriptase (RT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Potential glycan changes may alter RT activity.", "mechanism": "RT mutations and recombination increase viral replication and heterogeneity.", "protein": "Hepatitis B virus reverse transcriptase (RT)", "relationship_type": "causal", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Liver disease progression", "glycan_involvement": "Glycosylation state may influence immune clearance.", "mechanism": "Persistent HBsAg is associated with increased risk of liver disease.", "protein": "Hepatitis B virus surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Liver disease progression", "glycan_involvement": "Glycan modifications may impact RT stability.", "mechanism": "RT recombinants linked to higher HBV DNA and mutation rates, possibly affecting disease severity.", "protein": "Hepatitis B virus reverse transcriptase (RT)", "relationship_type": "causal", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Liver disease progression", "glycan_involvement": "Glycosylation may affect antigen secretion and immune response.", "mechanism": "HBeAg positivity correlates with active disease and progression risk.", "protein": "Hepatitis B virus e antigen (HBeAg)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Possible glycan changes at mutation sites.", "mechanism": "RT mutations (at rt53, 134, 213, 222, 271, 319, 340) are associated with recombinant HBV and higher viral load.", "protein": "Hepatitis B virus reverse transcriptase (RT)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "Glycosylation affects vaccine efficacy.", "mechanism": "HBsAg is a target for immunotherapy and vaccine development.", "protein": "Hepatitis B virus surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5631878" }, { "confidence": "medium", "disease": "Chronic hepatitis B", "glycan_involvement": "Glycan modifications may contribute to regional differences.", "mechanism": "Recombinant RT sequences are associated with geographic origin and disease heterogeneity.", "protein": "Hepatitis B virus reverse transcriptase (RT)", "relationship_type": "biomarker", "source_pmcid": "PMC5631878" }, { "confidence": "high", "disease": "Peritoneal fibrosis", "glycan_involvement": "FN1 is a glycoprotein; glycosylation affects matrix assembly and cell adhesion.", "mechanism": "Upregulated by 5-HT stimulation in HPFB, contributing to extracellular matrix accumulation.", "protein": "Fibronectin (FN1)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "high", "disease": "Peritoneal fibrosis", "glycan_involvement": "Collagen glycosylation modulates fibril formation and tissue stiffness.", "mechanism": "5-HT increases Col1a1/Col1a2 expression, promoting fibrosis; antagonists reduce this effect.", "protein": "Type I Collagen (Col1a1, Col1a2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Peritoneal fibrosis", "glycan_involvement": "CTGF glycosylation influences secretion and activity.", "mechanism": "CTGF upregulated by 5-HT, mediates fibroblast activation and matrix synthesis.", "protein": "Connective Tissue Growth Factor (CTGF)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "high", "disease": "Peritoneal fibrosis", "glycan_involvement": "TGF-\u03b21 glycosylation affects receptor binding and signaling.", "mechanism": "5-HT induces TGF-\u03b21 expression, driving pro-fibrotic gene activation.", "protein": "Transforming Growth Factor Beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Peritoneal fibrosis", "glycan_involvement": "ACTA2 is glycosylated, influencing filament assembly.", "mechanism": "Increased ACTA2 indicates myofibroblast differentiation in fibrosis.", "protein": "Alpha-Smooth Muscle Actin (ACTA2)", "relationship_type": "biomarker", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Ultrafiltration failure in CAPD", "glycan_involvement": "FN1 glycosylation modulates matrix interactions.", "mechanism": "FN1 accumulation contributes to peritoneal membrane thickening and ultrafiltration failure.", "protein": "Fibronectin (FN1)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Ultrafiltration failure in CAPD", "glycan_involvement": "Collagen glycosylation affects matrix structure.", "mechanism": "Collagen deposition impairs peritoneal membrane function.", "protein": "Type I Collagen (Col1a1, Col1a2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Peritoneal fibrosis", "glycan_involvement": "MMP2 glycosylation regulates enzyme activity.", "mechanism": "MMP2 expression is anti-fibrotic, involved in matrix degradation.", "protein": "Matrix Metalloproteinase 2 (MMP2)", "relationship_type": "protective", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Peritoneal fibrosis", "glycan_involvement": "TIMP1 glycosylation affects inhibitory function.", "mechanism": "TIMP1 inhibits MMP2, favoring matrix accumulation and fibrosis.", "protein": "Tissue Inhibitor of Metalloproteinases 1 (TIMP1)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "medium", "disease": "Ultrafiltration failure in CAPD", "glycan_involvement": "Glycosylation modulates TGF-\u03b21 signaling.", "mechanism": "TGF-\u03b21 upregulation leads to excessive matrix synthesis and membrane dysfunction.", "protein": "Transforming Growth Factor Beta 1 (TGF-\u03b21)", "relationship_type": "causal", "source_pmcid": "PMC5727888" }, { "confidence": "high", "disease": "Chronic Hepatitis C Virus Infection", "glycan_involvement": "N-glycosylation of E1/E2 is essential for proper folding, immune evasion, and infectivity.", "mechanism": "E1/E2 glycoproteins mediate viral entry into hepatocytes, driving chronic infection.", "protein": "Hepatitis C Virus Envelope Glycoproteins (E1/E2)", "relationship_type": "causal", "source_pmcid": "PMC5727889" }, { "confidence": "high", "disease": "Biotinidase deficiency", "glycan_involvement": "Biotinidase is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Deficiency of biotinidase leads to impaired recycling of biotin, causing metabolic dysfunction.", "protein": "Biotinidase", "relationship_type": "causal", "source_pmcid": "PMC5751534" }, { "confidence": "high", "disease": "Lysosomal storage diseases (Pompe, Niemann-Pick, Fabry, Krabbe, MPS I, Gaucher)", "glycan_involvement": "N-glycosylation is critical for lysosomal targeting and enzyme activity.", "mechanism": "Deficiency or malfunction of specific lysosomal glycoproteins leads to substrate accumulation.", "protein": "Lysosomal enzymes (e.g., alpha-glucosidase, beta-glucocerebrosidase, alpha-galactosidase)", "relationship_type": "causal", "source_pmcid": "PMC5751534" }, { "confidence": "medium", "disease": "Cobalamin deficiency", "glycan_involvement": "Glycosylation affects protein stability and receptor-mediated uptake.", "mechanism": "Defects in cobalamin-binding glycoproteins impair vitamin B12 absorption and transport.", "protein": "Cobalamin-binding proteins", "relationship_type": "causal/biomarker", "source_pmcid": "PMC5751534" }, { "confidence": "medium", "disease": "Folate deficiency", "glycan_involvement": "Glycosylation modulates binding affinity and transport.", "mechanism": "Altered glycoprotein function affects folate uptake in mammary glands and other tissues.", "protein": "Folate-binding proteins", "relationship_type": "causal/biomarker", "source_pmcid": "PMC5751534" }, { "confidence": "medium", "disease": "Multiple carboxylase deficiency", "glycan_involvement": "Glycosylation is important for enzyme stability and activity.", "mechanism": "Deficiency of glycoprotein carboxylases impairs metabolism of amino/fatty acids.", "protein": "Multiple carboxylase enzymes", "relationship_type": "causal", "source_pmcid": "PMC5751534" }, { "confidence": "high", "disease": "Transferrin-related disorders", "glycan_involvement": "N-glycosylation pattern is diagnostic.", "mechanism": "Altered glycosylation of transferrin is a diagnostic marker for congenital disorders of glycosylation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC5751534" }, { "confidence": "medium", "disease": "Immune deficiency", "glycan_involvement": "N-glycosylation modulates antibody effector functions.", "mechanism": "Glycosylation defects in immunoglobulins can impair immune function.", "protein": "Immunoglobulins", "relationship_type": "causal/biomarker", "source_pmcid": "PMC5751534" }, { "confidence": "high", "disease": "Multiple sclerosis (pediatric)", "glycan_involvement": "Glycosylation affects pharmacokinetics and immunogenicity.", "mechanism": "Beta-interferon, a glycoprotein, is used as immunomodulatory therapy to reduce relapse rate.", "protein": "Beta-interferon", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5751534" }, { "confidence": "medium", "disease": "Multiple sclerosis (pediatric)", "glycan_involvement": "Glycosylation may affect immune modulation.", "mechanism": "Glatiramer acetate modulates immune response via induction of regulatory glycoproteins.", "protein": "Glatiramer acetate-induced glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5751534" }, { "confidence": "high", "disease": "Multiple sclerosis (pediatric)", "glycan_involvement": "Fc glycosylation impacts efficacy and safety.", "mechanism": "Natalizumab, a glycosylated monoclonal antibody, blocks lymphocyte migration into CNS.", "protein": "Natalizumab (anti-\u03b14 integrin antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5751534" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation modulates integrin function and ligand binding.", "mechanism": "\u03b1v\u03b23 integrin is upregulated in tumor angiogenesis and is targeted for imaging and therapy.", "protein": "\u03b1v\u03b23 integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC5843810" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "N-glycosylation affects PSMA stability and cell surface expression.", "mechanism": "PSMA is highly expressed on prostate cancer cells and targeted for imaging and therapy.", "protein": "PSMA", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Glycosylation may influence receptor trafficking and ligand binding.", "mechanism": "NPY-Y1R is overexpressed in breast cancer and targeted for PET imaging.", "protein": "NPY-Y1 receptor", "protein_enriched": { "function": "Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] ", "gene_name": "NPY1R", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P25929" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "high", "disease": "HER2-positive breast cancer", "glycan_involvement": "N-glycosylation modulates HER2 dimerization and signaling.", "mechanism": "HER2 is overexpressed in a subset of breast cancers and targeted by trastuzumab and imaging agents.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "medium", "disease": "Angiogenesis-related diseases", "glycan_involvement": "Glycosylation affects VEGF secretion and receptor binding.", "mechanism": "VEGF165 promotes angiogenesis in tumors and is targeted for imaging.", "protein": "VEGF165", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Glycosylation may affect receptor stability and ligand interaction.", "mechanism": "CCK2 receptor is expressed in certain tumors and targeted for imaging.", "protein": "CCK2 receptor", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences aggregation and clearance of \u03b2-amyloid.", "mechanism": "\u03b2-amyloid plaques are a hallmark of Alzheimer's disease and targeted for PET imaging.", "protein": "\u03b2-amyloid", "relationship_type": "biomarker", "source_pmcid": "PMC5843810" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "N-glycosylation modulates EGFR ligand binding and activation.", "mechanism": "EGFR is overexpressed in various cancers and targeted for imaging and therapy.", "protein": "EGF receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5843810" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation affects receptor function and ligand interaction.", "mechanism": "CSF-1R is expressed on macrophages and targeted for imaging of inflammatory processes.", "protein": "CSF-1R", "relationship_type": "biomarker", "source_pmcid": "PMC5843810" }, { "confidence": "medium", "disease": "Microglial activation", "glycan_involvement": "Glycosylation may regulate receptor expression and function.", "mechanism": "P2Y12 receptor is upregulated in anti-inflammatory microglia and targeted for imaging.", "protein": "P2Y12 receptor", "protein_enriched": { "function": "Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation", "gene_name": "P2RY12", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H244" }, "relationship_type": "biomarker", "source_pmcid": "PMC5843810" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Env is heavily glycosylated, and its glycan shield modulates immune recognition and viral infectivity.", "mechanism": "Env glycoprotein is expressed on the surface of HIV-infected cells and virions, serving as a marker for active viral replication and reservoir measurement.", "protein": "HIV Envelope Glycoprotein (Env)", "relationship_type": "biomarker", "source_pmcid": "PMC5851152" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "CFI is a glycoprotein; glycosylation affects its stability and activity in complement regulation.", "mechanism": "Up-regulation of CFI in serum is associated with poor treatment response, implicating complement pathway dysregulation.", "protein": "CFI", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "C4A is heavily glycosylated; glycosylation modulates immune complex formation and clearance.", "mechanism": "Elevated C4A levels in non-responders suggest classical complement pathway involvement in disease and treatment response.", "protein": "C4A", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "C6 glycosylation is important for MAC assembly and function.", "mechanism": "Increased C6, a MAC component, indicates enhanced complement-mediated cytolysis in poor responders.", "protein": "C6", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "F9 glycosylation affects secretion and coagulation activity.", "mechanism": "Up-regulation of F9 links intrinsic coagulation pathway activation to schizophrenia treatment response.", "protein": "F9", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "VWF is highly glycosylated; glycosylation regulates multimerization and platelet binding.", "mechanism": "Elevated VWF suggests endothelial dysfunction and altered coagulation in schizophrenia.", "protein": "VWF", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation of SERPING1 is critical for its inhibitory function.", "mechanism": "SERPING1 up-regulation reflects increased inhibition of complement activation in poor responders.", "protein": "SERPING1", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Psychotic experiences (risk state)", "glycan_involvement": "Glycosylation modulates C4A immune functions.", "mechanism": "Up-regulation of C4A in individuals at risk for psychosis supports complement involvement in disease onset.", "protein": "C4A", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "medium", "disease": "Schizophreniform disorder", "glycan_involvement": "Glycosylation affects CFI protease activity.", "mechanism": "CFI elevation in serum is linked to poor response in first episode schizophreniform disorder.", "protein": "CFI", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "low", "disease": "Psychotic experiences (risk state)", "glycan_involvement": "Glycosylation required for MAC formation.", "mechanism": "Increased C6 may indicate complement activation in individuals at risk for psychosis.", "protein": "C6", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "low", "disease": "Schizophreniform disorder", "glycan_involvement": "Glycosylation controls VWF function and clearance.", "mechanism": "VWF up-regulation may reflect vascular or coagulation changes in early psychosis.", "protein": "VWF", "relationship_type": "biomarker", "source_pmcid": "PMC5888760" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "Fibronectin glycosylation may affect EV cargo and antibody binding.", "mechanism": "Fibronectin in EVs binds bevacizumab, contributing to resistance in glioblastoma.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). 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Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates galectin binding and immune signaling.", "mechanism": "Exosomal LGALS3BP associated with diabetes development.", "protein": "LGALS3BP (Galectin-3-binding protein)", "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "high", "disease": "Type 1 Diabetes", "glycan_involvement": "Glycosylation affects lactadherin binding to EVs.", "mechanism": "Lactadherin detects procoagulant phosphatidylserine on EVs; higher PS concentration in T1D patients.", "protein": "Lactadherin", "protein_enriched": { "function": "Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization (By similarity). Contributes to phagocy", "gene_name": "MFGE8", "glycan_count": 69, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01650EU", "G02402FF", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G10773YW", "G14260UH", "G20210JR", "G23294PN", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G48584BU", "G49018RC", "G51640FO", "G51653BI", "G54010QB", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G66538GV", "G70101JE", "G72291OX", "G72735IY", "G72747WU", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G92406TI", "G95865ZB", "G49108TO", "G04657PL", "G08146BT", "G20706XG", "G22310AV", "G23863VK", "G25451PN", "G41071NU", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46691LC", "G51413EV", "G57776ZS", "G57818FI", "G64162JC", "G71146HJ", "G75983OB", "G79666IR", "G81263BG", "G83229XP", "G84452RH", "G86226EA" ], "uniprot_id": "Q08431" }, "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Glycosylation may modulate annexin A5-EV interactions.", "mechanism": "Annexin A5-bound MSC-EVs show enhanced anti-inflammatory effects in colitis model.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "therapeutic", "source_pmcid": "PMC5933288" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation influences SPARC secretion and function.", "mechanism": "SPARC in myotube exosomes linked to diabetes development.", "protein": "SPARC", "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation affects thrombospondin-5 structure and EV loading.", "mechanism": "Thrombospondin-5 in brown adipocyte exosomes associated with metabolic disease.", "protein": "Thrombospondin-5", "protein_enriched": { "function": "Probable hormone that may attenuate cell proliferation and induce senescence of oligodendrocyte and neural precursor cells in the central nervous system (By similarity). ECRG4-induced senescence is ch", "gene_name": "ECRG4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H1Z8" }, "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "EGFR glycosylation modulates ligand binding and EV sorting.", "mechanism": "EGFR uniquely present in hepatocyte exosomes; potential role in cancer signaling.", "protein": "Epidermal Growth Factor Receptor (EGFR)", "relationship_type": "therapeutic target", "source_pmcid": "PMC5933288" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation regulates serpin stability and secretion.", "mechanism": "Serpin proteins in hepatocyte and muscle exosomes linked to metabolic disease.", "protein": "Serpin family proteins", "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "Glycosylation affects lactadherin-EV binding and procoagulant activity.", "mechanism": "Loss of low PS concentration on EVs in women with T1D may relate to increased CVD risk.", "protein": "Lactadherin", "protein_enriched": { "function": "Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization (By similarity). Contributes to phagocy", "gene_name": "MFGE8", "glycan_count": 69, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G01650EU", "G02402FF", "G02815KT", "G02886BB", "G05724UK", "G06110VR", "G10486CT", "G10773YW", "G14260UH", "G20210JR", "G23294PN", "G27058EU", "G28541PG", "G28681TP", "G31852PQ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G48584BU", "G49018RC", "G51640FO", "G51653BI", "G54010QB", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G66538GV", "G70101JE", "G72291OX", "G72735IY", "G72747WU", "G80920RR", "G80966KZ", "G82463GQ", "G83460ZZ", "G83633GK", "G90659AW", "G92050GC", "G92406TI", "G95865ZB", "G49108TO", "G04657PL", "G08146BT", "G20706XG", "G22310AV", "G23863VK", "G25451PN", "G41071NU", "G42962KI", "G43223CG", "G44215PV", "G45395BF", "G45495MK", "G46691LC", "G51413EV", "G57776ZS", "G57818FI", "G64162JC", "G71146HJ", "G75983OB", "G79666IR", "G81263BG", "G83229XP", "G84452RH", "G86226EA" ], "uniprot_id": "Q08431" }, "relationship_type": "biomarker", "source_pmcid": "PMC5933288" }, { "confidence": "high", "disease": "Wound healing", "glycan_involvement": "Polysaccharide-protein interaction modulates glycoprotein activity.", "mechanism": "EUP3 polysaccharide binds PDGF-BB, enhancing pro-angiogenic signaling for tissue regeneration.", "protein": "PDGF-BB", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "high", "disease": "Wound healing", "glycan_involvement": "Polysaccharide binding influences glycoprotein function.", "mechanism": "EUP3 polysaccharide binds FGF-2, promoting angiogenesis and tissue repair.", "protein": "FGF-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Post-translational modifications (glycosylation) may regulate activity.", "mechanism": "NF-\u03baB activation drives pro-inflammatory signaling; natural products can suppress its overactivation.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect nuclear localization and function.", "mechanism": "STAT3 mediates pro-inflammatory and oncogenic signaling; phytochemicals can modulate its activity.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Chronic inflammation", "glycan_involvement": "Keap1-Nrf2 complex stability may be glycosylation-dependent.", "mechanism": "Nrf2 activation upregulates antioxidant and anti-inflammatory genes, protecting against tissue damage.", "protein": "Nrf2", "protein_enriched": { "function": "Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase ", "gene_name": "Nfe2l2", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q60795" }, "relationship_type": "protective", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Plant defense (toxicity to pathogens)", "glycan_involvement": "Enzymes involved in glycosylation of alkaloids.", "mechanism": "ERF transcription factors regulate glycoalkaloid biosynthesis, conferring resistance to pathogens.", "protein": "SGA biosynthetic enzymes", "relationship_type": "protective", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Neurodegenerative cognitive impairment (Alzheimer's disease)", "glycan_involvement": "BChE is a glycoprotein; glycosylation affects inhibitor binding.", "mechanism": "Natural inhibitors (e.g., pteryxin, hyperforin) target BChE to improve cognitive function.", "protein": "BChE", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "ENaC glycosylation modulates channel activity.", "mechanism": "Flavonoids reduce ENaC expression via NKCC1 activation, lowering blood pressure.", "protein": "ENaC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "medium", "disease": "Acute lymphoblastic leukemia (ALL)", "glycan_involvement": "Steroid glycosylation may affect bioactivity.", "mechanism": "Androstane derivatives inhibit proliferation of ALL cells, overcoming dexamethasone resistance.", "protein": "Novel androstane derivatives", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "high", "disease": "Wound healing", "glycan_involvement": "Carbohydrate-protein interactions modulate glycoprotein function.", "mechanism": "Polysaccharide enhances growth factor activity for angiogenesis and tissue repair.", "protein": "EUP3 polysaccharide-binding proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC5954276" }, { "confidence": "high", "disease": "Neuroinflammation", "glycan_involvement": "TSPO is a glycoprotein; glycosylation may affect its cell surface localization and function.", "mechanism": "TSPO upregulation indicates microglial activation and neuroinflammation after BBB disruption.", "protein": "Translocator Protein (TSPO)", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "SNCA is glycosylated; glycosylation modulates aggregation propensity and toxicity.", "mechanism": "Overexpression and aggregation of \u03b1-synuclein leads to neuronal degeneration in PD.", "protein": "Alpha-synuclein (SNCA)", "relationship_type": "causal", "source_pmcid": "PMC5975280" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau glycosylation affects phosphorylation and aggregation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to cognitive decline.", "protein": "Tau protein (MAPT)", "relationship_type": "causal", "source_pmcid": "PMC5975280" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CD68 is heavily glycosylated; glycosylation regulates its lysosomal targeting and function.", "mechanism": "CD68 marks activated microglia in regions of tau redistribution after BBB opening.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "medium", "disease": "Neuroinflammation", "glycan_involvement": "Iba1 is glycosylated; glycosylation may affect microglial activation.", "mechanism": "Iba1 upregulation indicates microglial activation post BBB disruption.", "protein": "Iba1 (AIF1)", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "medium", "disease": "Glioblastoma multiforme", "glycan_involvement": "Glycosylation may regulate TSPO function in tumor microenvironment.", "mechanism": "TSPO upregulation is associated with microglial activation in GBM peritumoral regions.", "protein": "TSPO", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "low", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates aggregation and toxicity.", "mechanism": "\u03b1-synuclein aggregates may be present in AD brains, contributing to pathology.", "protein": "Alpha-synuclein (SNCA)", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation affects tau aggregation.", "mechanism": "Tau pathology may overlap with PD in some cases.", "protein": "Tau protein (MAPT)", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "low", "disease": "Brain metastasis from breast cancer", "glycan_involvement": "Glycosylation may affect TSPO function in cancer.", "mechanism": "TSPO upregulation may indicate neuroinflammation in metastatic brain lesions.", "protein": "TSPO", "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "low", "disease": "Glioblastoma multiforme", "glycan_involvement": "Glycosylation regulates CD68 function.", "mechanism": "CD68 marks activated microglia/macrophages in GBM.", "protein": "CD68", "protein_enriched": { "function": "Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-spec", "gene_name": "CD68", "glycan_count": 63, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G88713AC", "G20706XG", "G96091TT", "G49108TO", "G04657PL", "G04672QB", "G05049YU", "G05962QB", "G07246CJ", "G08918WF", "G10819WX", "G11314AS", "G14972EH", "G18647XP", "G23719VF", "G23863VK", "G25418HZ", "G25451PN", "G27058EU", "G35541EV", "G36379GD", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G56307ZW", "G57776ZS", "G59626AS", "G60177UT", "G60834IK", "G62765YT", "G62894KT", "G63041LO", "G65184UU", "G66163OV", "G66621EA", "G70441OD", "G72797UR", "G79666IR", "G80075MS", "G80223IX", "G80479JV", "G81263BG", "G82463GQ", "G82830MN", "G83646BJ", "G84452RH", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G90659AW", "G92275SC", "G93718GY", "G95177YH", "G95865ZB", "G96577RX", "G58087IP", "G70101JE" ], "uniprot_id": "P34810" }, "relationship_type": "biomarker", "source_pmcid": "PMC5975280" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry into host cells via sialic acid binding.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosylation affects receptor interaction and immune recognition.", "mechanism": "Facilitates viral entry by binding to host cell receptors.", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation influences infectivity and immune response.", "mechanism": "Mediates viral attachment and fusion with host cells.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation modulates neurotropism and immune evasion.", "mechanism": "Essential for viral entry and neuroinvasion.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Coronavirus infection", "glycan_involvement": "Extensive glycosylation shields epitopes from immune detection.", "mechanism": "Binds to ACE2 receptor to mediate viral entry.", "protein": "Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosylation affects fusion efficiency and immune evasion.", "mechanism": "Promotes membrane fusion during viral entry.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation influences neurotropism and immunogenicity.", "mechanism": "Mediates viral attachment and entry into neurons.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Zika virus infection", "glycan_involvement": "N-glycosylation modulates infectivity and immune response.", "mechanism": "Facilitates viral entry and fusion.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Chikungunya", "glycan_involvement": "Glycosylation affects infectivity and immune evasion.", "mechanism": "Mediates viral entry and fusion.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation shields epitopes and modulates immune response.", "mechanism": "Binds to host cell receptors for viral entry.", "protein": "Envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6003050" }, { "confidence": "high", "disease": "Acute coronary syndrome", "glycan_involvement": "CXCR7 is a glycosylated chemokine receptor; glycosylation may affect ligand binding and receptor stability.", "mechanism": "CXCR7 agonism reduces platelet activation, thrombus formation, and thromboinflammation without affecting haemostasis.", "protein": "CXCR7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "Atherothrombosis", "glycan_involvement": "P2Y12 is a glycoprotein receptor; glycosylation may modulate receptor function.", "mechanism": "ADP-activated platelets via P2Y12 induce NETosis, contributing to atherothrombosis; inhibition by ticagrelor reduces NET formation.", "protein": "P2Y12", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "Major adverse cardiovascular events (MACE) after stenting", "glycan_involvement": "PEAR1 is a transmembrane glycoprotein; glycosylation may affect receptor signaling.", "mechanism": "PEAR1 rs12041331 A/A genotype is associated with increased risk of MACE and altered platelet reactivity.", "protein": "PEAR1", "protein_enriched": { "function": "Involved in the mineralization and structural organization of enamel", "gene_name": "AMBN", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q9NP70" }, "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "Clopidogrel response variability", "glycan_involvement": "B4GALT2 mediates galactosylation of glycoproteins, impacting integrin and receptor function.", "mechanism": "B4GALT2 c.909C>T variant predicts lower platelet reactivity on clopidogrel, possibly via altered glycosylation of platelet surface proteins.", "protein": "B4GALT2", "protein_enriched": { "function": "Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts", "gene_name": "B4GALT7", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBV7" }, "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "PT-VWD (Platelet-type von Willebrand Disease)", "glycan_involvement": "GP1BA is heavily glycosylated; glycosylation affects vWF binding and platelet adhesion.", "mechanism": "GP1BA gene mutation causes PT-VWD, leading to abnormal platelet-vWF interaction and bleeding.", "protein": "GP1BA", "relationship_type": "causal", "source_pmcid": "PMC6032109" }, { "confidence": "medium", "disease": "Peripheral artery disease", "glycan_involvement": "GPIIIa glycosylation modulates integrin activation and platelet aggregation.", "mechanism": "Leu33Pro polymorphism in GPIIIa is associated with altered platelet reactivity and response to antiplatelet therapy in PAD.", "protein": "GPIIIa (ITGB3)", "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "medium", "disease": "Peripheral artery disease", "glycan_involvement": "GPIa glycosylation affects collagen binding and platelet function.", "mechanism": "C807T polymorphism in GPIa affects platelet adhesion and aggregation, influencing antiplatelet therapy response.", "protein": "GPIa (ITGA2)", "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "medium", "disease": "Thrombosis and cardiovascular disease", "glycan_involvement": "P-selectin is a glycoprotein; glycosylation is essential for its cell adhesion function.", "mechanism": "Platelet surface P-selectin expression correlates with platelet activation and thrombotic risk; anthocyanins reduce P-selectin expression.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "medium", "disease": "Blood loss in orthopedic surgery", "glycan_involvement": "\u03b2-thromboglobulin is glycosylated; glycosylation may affect its release and function.", "mechanism": "Preoperative \u03b2-thromboglobulin levels predict postoperative platelet activity and blood loss.", "protein": "\u03b2-thromboglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "Thrombocytopenia in chronic liver disease", "glycan_involvement": "MPL is a glycoprotein; glycosylation is important for receptor expression and signaling.", "mechanism": "Avatrombopag, a thrombopoietin receptor agonist, increases platelet counts in CLD-associated thrombocytopenia.", "protein": "Thrombopoietin receptor (MPL)", "protein_enriched": { "function": "Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. Upon activation by THPO, induces rapid tyrosine phosphorylation and a", "gene_name": "MPL", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G25637MV" ], "uniprot_id": "P40238" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6032109" }, { "confidence": "high", "disease": "Celiac disease", "glycan_involvement": "Glycosylation affects zonulin secretion and function.", "mechanism": "Zonulin regulates intestinal permeability, increased levels lead to loss of barrier function and antigen trafficking, triggering autoimmune response.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "causal", "source_pmcid": "PMC6153547" }, { "confidence": "high", "disease": "Chronic inflammatory diseases (CID)", "glycan_involvement": "Glycosylation modulates zonulin activity.", "mechanism": "Elevated zonulin increases gut permeability, allowing antigens to cross and activate immune responses.", "protein": "Zonulin", "protein_enriched": { "function": "Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required", "gene_name": "CCDC61", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Y6R9" }, "relationship_type": "causal", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Pain", "glycan_involvement": "Glycosylation required for receptor binding and activity.", "mechanism": "Cholecystokinin modulates pain perception via neural networks.", "protein": "Cholecystokinin", "protein_enriched": { "function": "This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release fr", "gene_name": "CCK", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P06307" }, "relationship_type": "modulatory", "source_pmcid": "PMC6153547" }, { "confidence": "high", "disease": "Pain", "glycan_involvement": "Glycosylation affects receptor localization and signaling.", "mechanism": "Opioid receptor activation reduces pain; placebo and drug effects converge on these pathways.", "protein": "Opioid receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Parkinson\u2019s disease", "glycan_involvement": "Glycosylation influences receptor function.", "mechanism": "Dopamine receptor signaling in basal ganglia is central to Parkinson\u2019s disease symptoms and placebo responsiveness.", "protein": "Dopamine receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Pain", "glycan_involvement": "Glycosylation impacts enzyme stability and activity.", "mechanism": "COX enzymes mediate inflammatory pain; targeted by drugs and placebo effects.", "protein": "Cyclooxygenase (COX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Pain", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Cannabinoid receptor signaling modulates pain and is involved in placebo response.", "protein": "Cannabinoid receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Chronic inflammatory diseases (CID)", "glycan_involvement": "Glycosylation determines antigen recognition and immune signaling.", "mechanism": "Enterocyte glycoproteins regulate antigen sampling and trafficking, influencing tolerance vs. immunity.", "protein": "Enterocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Chronic inflammatory diseases (CID)", "glycan_involvement": "Glycosylation modulates antigen binding and immune activation.", "mechanism": "Dendritic cell glycoproteins mediate antigen uptake and presentation, affecting immune balance.", "protein": "Luminal dendritic cell glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC6153547" }, { "confidence": "medium", "disease": "Celiac disease", "glycan_involvement": "Glycosylation affects antibody effector function.", "mechanism": "Autoantibodies are produced in response to increased antigen trafficking due to gut permeability.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC6153547" }, { "confidence": "high", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Env is heavily glycosylated; glycans shield epitopes from neutralizing antibodies.", "mechanism": "Mediates viral entry via CD4 and co-receptor binding and membrane fusion.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "causal", "source_pmcid": "PMC6156844" }, { "confidence": "high", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Gag is not glycosylated, but interacts with glycoproteins during budding.", "mechanism": "Drives virus assembly and genomic RNA packaging.", "protein": "HIV-1 Gag precursor (Pr55 Gag)", "relationship_type": "causal", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "ESCRT-II subunits may be glycosylated, affecting complex stability and function.", "mechanism": "Required for efficient HIV-1 budding and release from host cells.", "protein": "ESCRT-II complex (EAP45)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "CypA is a glycoprotein; glycosylation may affect capsid interaction.", "mechanism": "Binds HIV-1 capsid, modulating uncoating and nuclear import.", "protein": "Cyclophilin A (CypA)", "protein_enriched": { "function": "Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic", "gene_name": "PPIA", "glycan_count": 8, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G27915IV", "G37995HC", "G49906RN", "G60033FS", "G62765YT", "G49108TO", "G70994MS", "G80920RR" ], "uniprot_id": "P62937" }, "relationship_type": "causal", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "Nup153 glycosylation may regulate nuclear pore function and viral genome entry.", "mechanism": "Facilitates HIV-1 nuclear import via capsid interaction.", "protein": "Nucleoporin Nup153", "protein_enriched": { "function": "Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are ", "gene_name": "SYNCRIP", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G27058EU", "G72747WU", "G49108TO" ], "uniprot_id": "O60506" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "CPSF6 glycosylation may modulate capsid binding.", "mechanism": "Binds HIV-1 capsid, influencing nuclear import and integration site selection.", "protein": "CPSF6", "protein_enriched": { "function": "Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional", "gene_name": "CPSF6", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16630" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "ALIX glycosylation may affect protein-protein interactions in budding.", "mechanism": "Links ESCRT-I/II to ESCRT-III, facilitating HIV-1 budding.", "protein": "ALIX", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6156844" }, { "confidence": "medium", "disease": "HIV-1 infection/AIDS", "glycan_involvement": "LEDGF/p75 glycosylation may influence chromatin binding.", "mechanism": "Tethers HIV-1 integrase to chromatin, guiding integration.", "protein": "LEDGF/p75", "protein_enriched": { "function": "Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by ", "gene_name": "PRDX4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13162" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6156844" }, { "confidence": "high", "disease": "HIV-1 integration site-related pathogenesis", "glycan_involvement": "IN is not glycosylated but interacts with glycoproteins (LEDGF/p75, Nup153).", "mechanism": "Catalyzes integration of viral DNA into host genome; integration site affects pathogenesis.", "protein": "HIV-1 Integrase (IN)", "relationship_type": "causal", "source_pmcid": "PMC6156844" }, { "confidence": "high", "disease": "HIV-1 immune escape", "glycan_involvement": "N-glycans mask neutralizing epitopes.", "mechanism": "Glycan shield on Env prevents antibody recognition, promoting immune escape.", "protein": "HIV-1 Envelope glycoprotein (Env)", "relationship_type": "protective (for virus)", "source_pmcid": "PMC6156844" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "U1-snRNP is a ribonucleoprotein complex with glycosylated protein components; glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against U1-snRNP are diagnostic markers for SLE and mixed connective tissue disease.", "protein": "U1 small nuclear ribonucleoprotein (U1-snRNP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6174655" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Many nuclear antigens targeted by ANA are glycoproteins; glycosylation can modulate immune recognition.", "mechanism": "ANA targets nuclear glycoproteins and is a hallmark of SLE diagnosis.", "protein": "Antinuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC6174655" }, { "confidence": "high", "disease": "Differentiated thyroid cancer", "glycan_involvement": "N-glycosylation affects thyroglobulin stability and secretion, impacting its reliability as a biomarker.", "mechanism": "Elevated serum thyroglobulin indicates recurrence or metastasis of thyroid cancer after thyroidectomy.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC6231292" }, { "confidence": "high", "disease": "Follicular thyroid cancer", "glycan_involvement": "Glycosylation modulates immunoreactivity and detection sensitivity in assays.", "mechanism": "Serum thyroglobulin is used to monitor disease status and detect metastasis in follicular thyroid cancer.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC6231292" }, { "confidence": "medium", "disease": "Chronic Obstructive Pulmonary Disease (COPD)", "glycan_involvement": "FGF21 is a glycoprotein; glycosylation may affect its secretion and stability.", "mechanism": "FGF21 expression correlates with myogenesis and myonuclear accretion during recovery from muscle metabolic stress in COPD patients.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation may regulate FGF21 bioactivity in muscle.", "mechanism": "FGF21 signaling mediates metabolic regulation of myonuclear accretion, potentially impacting muscle mass maintenance.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "GSK-3\u03b2 is a glycoprotein; glycosylation may modulate its activity.", "mechanism": "Inactivation of GSK-3\u03b2 increases PGC-1\u03b1 expression, enhancing mitochondrial biogenesis and muscle oxidative capacity.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "PGC-1\u03b1 is glycosylated, which may affect its stability and function.", "mechanism": "PGC-1\u03b1 upregulation promotes mitochondrial biogenesis and muscle function, counteracting sarcopenia.", "protein": "PGC-1\u03b1", "protein_enriched": { "function": "Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional act", "gene_name": "PPARGC1A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G31852PQ", "G49108TO" ], "uniprot_id": "Q9UBK2" }, "relationship_type": "protective/therapeutic_target", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "End Stage Renal Disease (ESRD)", "glycan_involvement": "BAIBA is a myokine; glycosylation may influence its secretion.", "mechanism": "Reduced plasma BAIBA levels are associated with physical inactivity and muscle mass decline in hemodialysis patients.", "protein": "BAIBA", "relationship_type": "biomarker", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation may regulate stability and activity of these factors.", "mechanism": "Exercise training increases expression of myogenic factors, improving muscle stem cell function and muscle regeneration in aging.", "protein": "Myogenic Regulatory Factors (MyoD, Myogenin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Primary Mitochondrial Myopathy (PMM)", "glycan_involvement": "Glycosylation may affect FGF21's diagnostic utility.", "mechanism": "FGF21 is a recognized biomarker for mitochondrial dysfunction in muscle.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC6240746" }, { "confidence": "medium", "disease": "Immunosenescence", "glycan_involvement": "Surface glycoproteins mediate T-cell senescence and immune dysfunction.", "mechanism": "Accumulation of glycosylated senescent T-cells is linked to immune aging and sarcopenia.", "protein": "Senescence-prone T-cell glycoproteins (e.g., CD57, KLRG1)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC6240746" }, { "confidence": "low", "disease": "Frailty", "glycan_involvement": "Glycosylation may regulate FGF21's circulating levels.", "mechanism": "FGF21 may reflect metabolic stress and muscle exhaustion in frailty.", "protein": "FGF21", "protein_enriched": { "function": "Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regula", "gene_name": "FGF21", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NSA1" }, "relationship_type": "biomarker", "source_pmcid": "PMC6240746" }, { "confidence": "low", "disease": "Frailty", "glycan_involvement": "Glycosylation may modulate GSK-3\u03b2's function in muscle.", "mechanism": "Targeting GSK-3\u03b2 may improve muscle mass and function in frailty via mitochondrial biogenesis.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6240746" }, { "confidence": "high", "disease": "Candidemia", "glycan_involvement": "Targets fungal glycan biosynthesis.", "mechanism": "Inhibits fungal cell wall synthesis via \u03b2-1,3-glucan synthase inhibition.", "protein": "Anidulafungin", "relationship_type": "therapeutic", "source_pmcid": "PMC6254033" }, { "confidence": "high", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation not directly involved in metabolism.", "mechanism": "Does not undergo hepatic metabolism, safe in liver impairment.", "protein": "Anidulafungin", "relationship_type": "protective", "source_pmcid": "PMC6254033" }, { "confidence": "high", "disease": "Renal Dysfunction", "glycan_involvement": "Glycosylation not directly involved in metabolism.", "mechanism": "Does not undergo renal metabolism, safe in kidney impairment.", "protein": "Anidulafungin", "relationship_type": "protective", "source_pmcid": "PMC6254033" }, { "confidence": "high", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "AST levels reflect liver cell injury.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC6254033" }, { "confidence": "high", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycosylation affects stability and secretion.", "mechanism": "ALT levels reflect liver cell injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6254033" }, { "confidence": "medium", "disease": "Hepatic Dysfunction", "glycan_involvement": "Glycoproteins involved in bilirubin transport.", "mechanism": "Elevated TB indicates impaired bilirubin clearance.", "protein": "TB", "relationship_type": "biomarker", "source_pmcid": "PMC6254033" }, { "confidence": "medium", "disease": "Renal Dysfunction", "glycan_involvement": "Glycoproteins in glomerular filtration barrier.", "mechanism": "eGFR estimates kidney filtration capacity.", "protein": "eGFR", "relationship_type": "biomarker", "source_pmcid": "PMC6254033" }, { "confidence": "low", "disease": "Solid Tumor", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Used in patients with solid tumors and candidemia.", "protein": "Anidulafungin", "relationship_type": "therapeutic (indirect)", "source_pmcid": "PMC6254033" }, { "confidence": "medium", "disease": "Liver Disease", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Safe antifungal in liver disease patients.", "protein": "Anidulafungin", "relationship_type": "therapeutic", "source_pmcid": "PMC6254033" }, { "confidence": "medium", "disease": "Kidney Disease", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Safe antifungal in kidney disease patients.", "protein": "Anidulafungin", "relationship_type": "therapeutic", "source_pmcid": "PMC6254033" }, { "confidence": "high", "disease": "Renal Fibrosis", "glycan_involvement": "CTGF is a secreted glycoprotein; glycosylation may affect its stability and function in fibrosis.", "mechanism": "CTGF expression is increased in venom-induced renal fibrosis; reduction after carnosine treatment indicates its role as a fibrosis marker.", "protein": "CTGF", "relationship_type": "biomarker", "source_pmcid": "PMC6306026" }, { "confidence": "high", "disease": "Renal Fibrosis", "glycan_involvement": "TGF-\u03b2 is glycosylated; glycosylation modulates its secretion and activity in fibrosis.", "mechanism": "TGF-\u03b2 upregulation promotes fibrotic changes in kidney after venom exposure; carnosine reduces its expression.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may regulate CTGF's extracellular matrix interactions in AKI.", "mechanism": "CTGF levels increase in AKI induced by snake venom; reduction after carnosine treatment suggests involvement in AKI pathology.", "protein": "CTGF", "relationship_type": "biomarker", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation affects TGF-\u03b2's receptor binding and signaling in AKI.", "mechanism": "TGF-\u03b2 mediates inflammatory and fibrotic responses in AKI; carnosine reduces its expression.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation may influence CTGF's inflammatory signaling.", "mechanism": "CTGF is upregulated in venom-induced renal inflammation; carnosine reduces its expression.", "protein": "CTGF", "relationship_type": "biomarker", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates TGF-\u03b2's immune regulatory functions.", "mechanism": "TGF-\u03b2 drives inflammatory processes in venom-induced kidney injury.", "protein": "TGF-\u03b2", "relationship_type": "causal", "source_pmcid": "PMC6306026" }, { "confidence": "high", "disease": "Renal Fibrosis", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "\u03b1-SMA marks myofibroblast activation in renal fibrosis; increased after venom, reduced by carnosine.", "protein": "\u03b1-SMA", "relationship_type": "biomarker", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Renal Fibrosis", "glycan_involvement": "Glycosylation may affect CTGF's therapeutic targeting.", "mechanism": "Reduction of CTGF by carnosine suggests CTGF as a therapeutic target in fibrosis.", "protein": "CTGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Renal Fibrosis", "glycan_involvement": "Glycosylation impacts TGF-\u03b2's therapeutic modulation.", "mechanism": "Carnosine's effect on TGF-\u03b2 suggests its potential as a therapeutic target in fibrosis.", "protein": "TGF-\u03b2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Renal Fibrosis", "glycan_involvement": "Glycosylation may modulate CTGF's protective response.", "mechanism": "Carnosine reduces CTGF expression, providing protection against fibrosis.", "protein": "CTGF", "relationship_type": "protective", "source_pmcid": "PMC6306026" }, { "confidence": "medium", "disease": "Early-onset peritonitis in peritoneal dialysis patients", "glycan_involvement": "Albumin is a glycoprotein; altered glycosylation may affect its stability and immune functions.", "mechanism": "Hypoalbuminemia is associated with increased risk of early-onset peritonitis, possibly reflecting poor nutritional status and impaired immune defense.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC6306027" }, { "confidence": "high", "disease": "Differentiated Thyroid Cancer", "glycan_involvement": "N-glycosylation affects thyroglobulin stability and secretion, impacting its detectability as a biomarker.", "mechanism": "Elevated serum thyroglobulin indicates recurrence or metastasis of thyroid cancer after thyroidectomy.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC6354729" }, { "confidence": "high", "disease": "Follicular Thyroid Cancer", "glycan_involvement": "Glycosylation modulates immunoreactivity and serum half-life of thyroglobulin.", "mechanism": "Thyroglobulin levels are used to monitor disease status and recurrence in follicular thyroid cancer.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC6354729" }, { "confidence": "high", "disease": "Cachexia", "glycan_involvement": "Serpina3n is a glycoprotein; glycosylation may affect its stability and secretion.", "mechanism": "Serpina3n is strongly upregulated in muscle during cancer-induced cachexia and correlates with body weight loss and survival.", "protein": "Serpina3n", "protein_enriched": { "function": "Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation", "gene_name": "Hpx", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G90659AW", "G42860KJ", "G22990JP", "G49108TO" ], "uniprot_id": "Q91X72" }, "relationship_type": "biomarker", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "STAT3 activation regulates glycoprotein expression including Serpina3n.", "mechanism": "Cancer activates acute phase response via STAT3, leading to muscle wasting.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Hypertension-induced muscle atrophy", "glycan_involvement": "Catalase is glycosylated, which affects its activity and stability.", "mechanism": "Physical exercise increases catalase activity, reducing oxidative stress in hypertensive muscle.", "protein": "Catalase", "protein_enriched": { "function": "Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth o", "gene_name": "Cat", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P24270" }, "relationship_type": "protective", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Hypertension-induced muscle atrophy", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "Exercise upregulates superoxide dismutase, improving muscle antioxidant defense.", "protein": "Superoxide dismutase", "relationship_type": "protective", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Hypertension-induced muscle atrophy", "glycan_involvement": "Glycosylation affects enzyme function.", "mechanism": "Exercise increases glutathione peroxidase, reducing muscle oxidative damage.", "protein": "Glutathione peroxidase", "protein_enriched": { "function": "Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such ", "gene_name": "GPX1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P07203" }, "relationship_type": "protective", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Protein energy wasting (PEW) in CKD", "glycan_involvement": "Albumin glycosylation status may reflect inflammation and nutritional state.", "mechanism": "Low serum albumin is associated with malnutrition and poor outcomes in CKD.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "CKD and physical dysfunction", "glycan_involvement": "Glycosylation modulates binding affinity and serum half-life.", "mechanism": "Vitamin D binding protein levels affect vitamin D status, impacting muscle function in CKD.", "protein": "Vitamin D binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Sarcopenia in CKD", "glycan_involvement": "Cell membrane glycoproteins contribute to phase angle measurement.", "mechanism": "Phase angle reflects cell membrane integrity, correlating with muscle function and nutritional status.", "protein": "Phase angle (cell membrane glycoproteins)", "relationship_type": "biomarker", "source_pmcid": "PMC6448808" }, { "confidence": "medium", "disease": "Insulin resistance in critical illness", "glycan_involvement": "N-glycosylation of insulin receptor is essential for its function.", "mechanism": "Impaired insulin receptor function leads to reduced glucose disposal in muscle during critical illness.", "protein": "Insulin receptor", "relationship_type": "causal", "source_pmcid": "PMC6448808" }, { "confidence": "high", "disease": "Cancer cachexia", "glycan_involvement": "ACVR2B is a glycoprotein; glycosylation affects ligand binding and receptor signaling.", "mechanism": "Blocking ACVR2B ligands prevents muscle wasting and improves survival in cancer cachexia models.", "protein": "Activin receptor type IIB (ACVR2B)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6448808" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "NID1 is a glycoprotein; glycosylation may affect exosomal packaging and interaction with fibroblasts.", "mechanism": "Exosomal NID1 promotes HCC metastasis by activating lung fibroblasts to secrete TNFR1, enhancing tumor cell motility.", "protein": "Nidogen 1 (NID1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "high", "disease": "Bladder cancer", "glycan_involvement": "CD63 glycosylation may influence exosome formation and stability.", "mechanism": "Urinary exosomal CD63 used as a marker in a 16-mRNA signature for noninvasive bladder cancer diagnosis.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "CD45 glycosylation affects EV surface recognition.", "mechanism": "Increased CD45+ EVs in urine of symptomatic CAD patients; potential diagnostic/prognostic marker.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "CD61 glycosylation may affect EV release and function.", "mechanism": "Platelet-derived EVs (CD61+) altered in CAD; decrease after remote ischemic preconditioning.", "protein": "CD61", "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "CD14 glycosylation may impact EV cargo sorting.", "mechanism": "Monocyte/macrophage marker on urinary EVs; altered expression in CAD.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "TNFR1 glycosylation may regulate receptor shedding and activity.", "mechanism": "Secreted by lung fibroblasts activated by exosomal NID1; promotes HCC cell motility and metastasis.", "protein": "Tumor Necrosis Factor Receptor 1 (TNFR1)", "relationship_type": "causal", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "Coronary artery disease (CAD)", "glycan_involvement": "Integrin glycosylation modulates EV-cell interactions.", "mechanism": "Surface markers on urinary EVs; altered integrin expression in symptomatic CAD.", "protein": "Alpha/Beta Integrins", "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "high", "disease": "Glioblastoma", "glycan_involvement": "MGMT glycosylation not directly discussed; methylation status is key.", "mechanism": "MGMT methylation status detected in EV DNA; used for glioblastoma classification and therapy stratification.", "protein": "MGMT", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "Alzheimer's disease (AD)", "glycan_involvement": "CD63 glycosylation may affect exosome targeting and cargo.", "mechanism": "Serum exosomal CD63 used for isolation and profiling of miRNA biomarkers for AD diagnosis.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "medium", "disease": "End-stage renal disease (ESRD)", "glycan_involvement": "CD45 glycosylation may influence EV immune interactions.", "mechanism": "Circulating CD45+ EVs increased in diabetic ESRD patients; associated with cardiovascular complications.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC6493311" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to sialic acid receptors on host cells.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield protects from neutralizing antibodies.", "mechanism": "Facilitates viral attachment and entry via CD4 and co-receptors.", "protein": "Envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor binding and immune recognition.", "mechanism": "Binds ACE2 receptor to mediate viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Herpes simplex", "glycan_involvement": "Glycosylation influences receptor binding and immune evasion.", "mechanism": "Essential for viral entry via interaction with host receptors.", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "Glycosylation required for secretion and immune modulation.", "mechanism": "Secreted NS1 detected in patient serum as diagnostic marker.", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects immunogenicity and viral infectivity.", "mechanism": "Mediates viral attachment and fusion with host cells.", "protein": "Glycoprotein G", "protein_enriched": { "function": "Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopm", "gene_name": "UL32", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08318" }, "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Cytomegalovirus infection", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Targeted by neutralizing antibodies and vaccines.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Varicella zoster", "glycan_involvement": "Glycosylation affects immunogenicity.", "mechanism": "Major target for vaccine-induced immunity.", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6517453" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation influences host cell tropism.", "mechanism": "Mediates viral entry and fusion.", "protein": "Envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "high", "disease": "Ebola", "glycan_involvement": "Glycan cap shields epitopes from immune detection.", "mechanism": "Mediates viral entry and immune evasion.", "protein": "Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC6517453" }, { "confidence": "medium", "disease": "Fulminant type 1 diabetes mellitus (FT1DM)", "glycan_involvement": "Beta 2 glycoprotein is heavily glycosylated, which affects its immunogenicity.", "mechanism": "Antibody to beta 2 glycoprotein tested as part of autoimmune workup; negative result helps exclude antiphospholipid syndrome.", "protein": "beta 2 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC6550715" }, { "confidence": "high", "disease": "Fulminant type 1 diabetes mellitus (FT1DM)", "glycan_involvement": "ZnT8 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Presence of ZnT8 autoantibodies indicates autoimmune destruction of beta cells.", "protein": "ZnT8 (Zinc transporter 8)", "relationship_type": "biomarker", "source_pmcid": "PMC6550715" }, { "confidence": "high", "disease": "Fulminant type 1 diabetes mellitus (FT1DM)", "glycan_involvement": "GAD is glycosylated, which may influence immune recognition.", "mechanism": "GAD autoantibodies are markers of autoimmune beta cell destruction.", "protein": "GAD (Glutamic acid decarboxylase)", "protein_enriched": { "function": "Catalyzes the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with pyridoxal 5'-phosphate as cofactor", "gene_name": "GAD1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99259" }, "relationship_type": "biomarker", "source_pmcid": "PMC6550715" }, { "confidence": "high", "disease": "Graves disease", "glycan_involvement": "TSHR glycosylation affects receptor conformation and autoantibody binding.", "mechanism": "Activating autoantibodies (IgG) bind to TSHR, stimulating thyroid hormone production.", "protein": "Thyrotropin receptor (TSHR)", "relationship_type": "causal", "source_pmcid": "PMC6551903" }, { "confidence": "high", "disease": "Graves disease", "glycan_involvement": "IgG glycosylation modulates effector function and autoimmunity.", "mechanism": "Autoantibodies of IgG class target TSHR, indicating disease presence.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6551903" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Altered IgG glycosylation may influence pathogenicity.", "mechanism": "Elevated serum IgG is a diagnostic marker for autoimmune hepatitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6551903" }, { "confidence": "medium", "disease": "Primary biliary cirrhosis", "glycan_involvement": "AMA glycosylation may affect antigen recognition.", "mechanism": "Presence of AMA is diagnostic for primary biliary cirrhosis.", "protein": "Antimitochondrial antibody (AMA)", "relationship_type": "biomarker", "source_pmcid": "PMC6551903" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "Shared glycosylation patterns may predispose to multiple autoimmune diseases.", "mechanism": "Patients with Graves disease (TSHR autoimmunity) are at increased risk for autoimmune hepatitis.", "protein": "Thyrotropin receptor (TSHR)", "relationship_type": "comorbidity", "source_pmcid": "PMC6551903" }, { "confidence": "low", "disease": "Primary biliary cirrhosis", "glycan_involvement": "IgG glycosylation influences immune response.", "mechanism": "Elevated IgG may be present in overlap syndromes.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6551903" }, { "confidence": "high", "disease": "LADA", "glycan_involvement": "DPP-4 is a glycoprotein; glycosylation affects its stability and immune interactions.", "mechanism": "DPP-4 inhibitors modulate immune response, shifting from Th1/Th17 to Th2/Treg, preserving \u03b2 cell function.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6553373" }, { "confidence": "high", "disease": "T1DM", "glycan_involvement": "Glycosylation of DPP-4 modulates its immunomodulatory activity.", "mechanism": "DPP-4 inhibitors (e.g., sitagliptin) prevent \u03b2 cell loss and promote immune tolerance.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6553373" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Glycosylation may affect DPP-4's immune cell interactions.", "mechanism": "DPP-4 inhibition reduces autoimmune inflammation.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6553373" }, { "confidence": "high", "disease": "LADA", "glycan_involvement": "GAD-65 is glycosylated; glycosylation may influence antigenicity.", "mechanism": "High GAD-65 antibody titers indicate autoimmune \u03b2 cell destruction.", "protein": "GAD-65", "relationship_type": "biomarker", "source_pmcid": "PMC6553373" }, { "confidence": "high", "disease": "T1DM", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "GAD-65 autoantibodies are diagnostic for autoimmune diabetes.", "protein": "GAD-65", "relationship_type": "biomarker", "source_pmcid": "PMC6553373" }, { "confidence": "medium", "disease": "LADA", "glycan_involvement": "Targets glycoproteins on islet cells.", "mechanism": "Presence of ICA indicates autoimmune attack on islet cells.", "protein": "ICA", "relationship_type": "biomarker", "source_pmcid": "PMC6553373" }, { "confidence": "medium", "disease": "LADA", "glycan_involvement": "IA-2 is glycosylated; glycosylation may affect antigenicity.", "mechanism": "IA-2 autoantibodies are markers of autoimmune diabetes.", "protein": "IA-2", "relationship_type": "biomarker", "source_pmcid": "PMC6553373" }, { "confidence": "low", "disease": "Inflammatory Arthritis", "glycan_involvement": "Glycosylation of DPP-4 may modulate immune effects.", "mechanism": "Vitamin D and DPP-4 inhibition prevent development of autoimmune arthritis in preclinical models.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "protective", "source_pmcid": "PMC6553373" }, { "confidence": "low", "disease": "Autoimmune Thyroiditis", "glycan_involvement": "Glycosylation may affect DPP-4's immunomodulatory role.", "mechanism": "Vitamin D supplementation prevents autoimmune thyroiditis, possibly via DPP-4 modulation.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "protective", "source_pmcid": "PMC6553373" }, { "confidence": "medium", "disease": "T1DM (prevention)", "glycan_involvement": "Glycosylation may influence DPP-4's immune function.", "mechanism": "DPP-4 inhibition prevents T1DM onset in NOD mice.", "protein": "Dipeptidyl Peptidase-4 (DPP-4/CD26)", "relationship_type": "protective", "source_pmcid": "PMC6553373" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation of platelet glycoproteins is essential for their stability and function in transfusion efficacy.", "mechanism": "Platelet glycoproteins mediate platelet function and are replenished via transfusion to treat thrombocytopenia.", "protein": "Platelet glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6573574" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects stability and localization of claudin-5 at tight junctions.", "mechanism": "Reduced expression/disruption of claudin-5 increases BBB permeability, facilitating amyloid beta entry.", "protein": "Claudin-5", "protein_enriched": { "function": "Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:23766516, PubMed:28209804, PubMed:909", "gene_name": "Acsl4", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O35547" }, "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates occludin trafficking and barrier function.", "mechanism": "Decreased occludin expression correlates with BBB leakiness and amyloid pathology.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorder", "glycan_involvement": "N-glycosylation regulates RAGE ligand binding and trafficking.", "mechanism": "RAGE mediates amyloid beta transfer via endothelial extracellular vesicles, promoting neuroinflammation.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC6584520" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation influences ApoA-I stability and HDL function.", "mechanism": "ApoA-I deficiency increases amyloid deposition and neuroinflammation; HDL/ApoA-I reduces amyloid pathology.", "protein": "ApoA-I", "relationship_type": "protective", "source_pmcid": "PMC6584520" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects BACE1 trafficking and activity.", "mechanism": "BACE1 promotes amyloid accumulation and tau hyperphosphorylation; knockdown reverses tauopathy and inflammation.", "protein": "BACE1", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation modulates VE-Cadherin adhesive function.", "mechanism": "WNT/\u03b2-catenin signaling from glioma stem cells reduces VE-Cadherin, disrupting endothelial junctions and increasing BBB permeability.", "protein": "VE-Cadherin", "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Sleep restriction-induced BBB dysfunction", "glycan_involvement": "Glycosylation affects Connexin 43 assembly and gap junction formation.", "mechanism": "Sleep restriction reduces Connexin 43, weakening endothelial-pericyte interactions and increasing BBB permeability.", "protein": "Connexin 43", "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "Glycosylation regulates PLVAP localization and fenestra formation.", "mechanism": "Increased PLVAP expression marks fenestration and BBB disruption under WNT/\u03b2-catenin signaling.", "protein": "PLVAP", "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates ICAM-1 cell adhesion and immune cell recruitment.", "mechanism": "ApoA-I deficiency elevates ICAM-1, indicating increased neuroinflammation and vascular dysfunction.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may affect GFAP filament assembly and astrocyte function.", "mechanism": "ApoA-I deficiency increases GFAP, reflecting astrocyte reactivity to amyloid and neuroinflammation.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC6584520" }, { "confidence": "medium", "disease": "Neuropsychiatric symptoms (including psychosis)", "glycan_involvement": "P-glycoprotein is a glycoprotein; glycosylation is important for its stability and function at the blood-brain barrier.", "mechanism": "Hydroxychloroquine may downregulate P-glycoprotein at the blood-brain barrier, potentially increasing CNS drug exposure and leading to neuropsychiatric side effects.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC6652516" }, { "confidence": "high", "disease": "Hepatitis E", "glycan_involvement": "IgG glycosylation affects antibody function and detection.", "mechanism": "Seroconversion indicates exposure and subclinical infection.", "protein": "Anti-HEV IgG", "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "IgG glycosylation modulates immune response.", "mechanism": "Presence indicates exposure and risk for chronic liver disease.", "protein": "Anti-HCV IgG", "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "CD4 glycosylation modulates T-cell activation.", "mechanism": "Decreased CD4+ T-cells in persistent hepatitis A cases.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "CD8 glycosylation affects cytotoxic function.", "mechanism": "Normal CD8+ T-cell levels in acute and persistent hepatitis A.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "medium", "disease": "Hepatitis A", "glycan_involvement": "CD56 glycosylation influences NK cell activity.", "mechanism": "Elevated NK cells in persistent hepatitis A suggest pathogenic role.", "protein": "Natural Killer cell marker (CD56)", "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AIH)", "glycan_involvement": "IgG glycosylation modulates autoantibody pathogenicity.", "mechanism": "Elevated IgG levels are diagnostic for AIH.", "protein": "Gamma-globulins (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Minor glycosylation may affect stability.", "mechanism": "ALT elevation reflects hepatocellular injury; decrease post-therapy indicates improvement.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Minor glycosylation may affect enzyme activity.", "mechanism": "AST elevation correlates with severity of DILI.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Drug-induced liver injury (DILI)", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "GGT elevation correlates with cholestatic/mixed DILI.", "protein": "Gamma-glutamyltransferase (GGT)", "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation affects secretion and activity.", "mechanism": "Prothrombin time used to assess liver synthetic function in HCV.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC6728869" }, { "confidence": "high", "disease": "Prion diseases (e.g., CJD, scrapie, BSE, CWD)", "glycan_involvement": "N-glycosylation and GPI-anchor critical for cell surface localization and infectivity.", "mechanism": "Misfolding and aggregation of PrP^C to PrP^Sc causes neurodegeneration.", "protein": "Prion protein (PrP, PrP^C/PrP^Sc)", "relationship_type": "causal", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is a glycoprotein; glycosylation may affect aggregation.", "mechanism": "Aggregated tau acts as a prion, spreading pathology; soluble tau fragments (e.g., \u0394tau314) are pathogenic.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 derived from APP, a glycoprotein; glycosylation of APP influences A\u03b2 production.", "mechanism": "A\u03b2 aggregation and plaque formation drive neurodegeneration; prion-like seeding accelerates pathology.", "protein": "Amyloid-beta (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Alpha-synuclein is a glycoprotein; glycosylation may modulate aggregation.", "mechanism": "Aggregated \u03b1-synuclein acts as a prion, propagating Lewy pathology.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Multiple system atrophy (MSA)", "glycan_involvement": "Glycosylation may influence prion properties.", "mechanism": "MSA brains contain \u03b1-synuclein prions; not found in AD brains.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD)", "glycan_involvement": "Glycosylation may affect tau prion formation.", "mechanism": "Tau prions detected in PSP/CBD brains; not A\u03b2 or \u03b1-synuclein prions.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC6738495" }, { "confidence": "medium", "disease": "Amyotrophic lateral sclerosis (ALS)", "glycan_involvement": "SOD1 is a glycoprotein; glycosylation status not detailed.", "mechanism": "Misfolded SOD1 propagates in a prion-like manner; W32 residue critical for templated misfolding.", "protein": "Superoxide dismutase 1 (SOD1)", "protein_enriched": { "function": "Destroys radicals which are normally produced within the cells and which are toxic to biological systems", "gene_name": "SOD1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G62894KT", "G70101JE", "G49108TO" ], "uniprot_id": "P00441" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Gerstmann-Str\u00e4ussler-Scheinker syndrome (GSS)-like prion disease", "glycan_involvement": "Mutant PrP lacks N-glycans and GPI-anchor, altering disease phenotype.", "mechanism": "Anchorless PrP Q227X mutant forms PrP^Sc but fails to recruit wild-type PrP^C; GPI-anchor is essential for propagation.", "protein": "Prion protein Q227X mutant", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6738495" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation of PrP^C on exosomes is crucial for A\u03b2 binding.", "mechanism": "Exosomal PrP^C accelerates A\u03b2 fibril formation by sequestering A\u03b2 oligomers, potentially neuroprotective.", "protein": "Prion protein (exosomal)", "relationship_type": "protective/causal", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation and GPI-anchor required for cell surface localization and function.", "mechanism": "Cell surface PrP^C acts as a receptor for A\u03b2 oligomers, initiating neurotoxic signaling.", "protein": "Prion protein (PrP^C)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC6738495" }, { "confidence": "high", "disease": "Non-Hodgkin Lymphoma", "glycan_involvement": "Glycosylation affects protein stability and drug binding", "mechanism": "Overexpression leads to drug resistance; targeted by polyamine-vectorized anticancer drug (F14512)", "protein": "P-Glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6766498" }, { "confidence": "medium", "disease": "Hypertrophic Cardiomyopathy", "glycan_involvement": "Glycosylation modulates cell-cell interactions", "mechanism": "Disorganization observed in affected cats; involved in cell adhesion and signaling", "protein": "\u03b2-Catenin", "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "high", "disease": "Solid Tumors", "glycan_involvement": "Glycosylation required for secretion and stability", "mechanism": "Serum levels elevated in dogs with neoplastic pericardial effusion and solid tumors", "protein": "C-Reactive Protein", "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "medium", "disease": "Solid Tumors", "glycan_involvement": "Glycosylation may affect enzyme activity", "mechanism": "Serum levels increased in dogs with solid tumors; used for disease detection", "protein": "Thymidine Kinase 1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "high", "disease": "Canine Hemangiosarcoma", "glycan_involvement": "Glycosylation impacts antigenicity and detection", "mechanism": "Overexpression allows for microscopic disease detection in blood", "protein": "Prostate Specific Membrane Antigen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "medium", "disease": "Histiocytic Sarcoma", "glycan_involvement": "Glycosylation influences secretion and immune modulation", "mechanism": "Expression and genetic variation associated with canine histiocytic sarcoma", "protein": "Apoptosis Inhibitor of Macrophage", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "high", "disease": "Cardiogenic Arterial Thromboembolism", "glycan_involvement": "Glycoproteins (e.g., histones, granule proteins) are core NET components", "mechanism": "NETs identified in feline arterial thromboembolism; contribute to thrombosis", "protein": "Neutrophil Extracellular Trap Components (NETs)", "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "medium", "disease": "Immune Mediated Disease", "glycan_involvement": "Glycosylation affects chemokine activity and receptor binding", "mechanism": "Serum CXCL10 levels altered in dogs with immune mediated disease", "protein": "CXCL10", "protein_enriched": { "function": "Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modul", "gene_name": "CXCL10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02778" }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "medium", "disease": "Bacterial Infection", "glycan_involvement": "Glycosylation modulates binding to heparin and immune cells", "mechanism": "Serum levels used as biomarker for bacterial infection in cats", "protein": "Heparin Binding Protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation required for secretion and renal filtration", "mechanism": "Serum levels used as early biomarker for chronic renal failure in dogs", "protein": "Cystatin C", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6766498" }, { "confidence": "high", "disease": "Congenital muscular dystrophy-dystroglycanopathy", "glycan_involvement": "Defective O-mannosylation of dystroglycan disrupts its function.", "mechanism": "Mutation in LARGE1 impairs glycosylation of dystroglycan, leading to muscular dystrophy and brain/eye anomalies.", "protein": "Dystroglycan (LARGE1-modified)", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "high", "disease": "Deafness-infertility syndrome", "glycan_involvement": "STRC is a glycoprotein required for hair cell function; glycosylation is essential for its stability.", "mechanism": "Homozygous deletion of STRC causes prelingual hearing loss.", "protein": "STRC (Stereocilin)", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "high", "disease": "Male infertility", "glycan_involvement": "CatSper2 is a glycoprotein; glycosylation may affect channel localization/function.", "mechanism": "Loss of CatSper2 impairs sperm Ca2+ channel function, leading to infertility.", "protein": "CatSper2", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "medium", "disease": "Recurrent pregnancy loss", "glycan_involvement": "ACKR3 is a glycoprotein; glycosylation may regulate receptor-ligand interactions.", "mechanism": "Duplication/aberrant expression of ACKR3 disrupts trophoblast-endometrial interaction.", "protein": "ACKR3/CXCR7", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency", "glycan_involvement": "N-glycosylation is critical for SERPINA1 secretion and stability.", "mechanism": "Mutations in SERPINA1 reduce glycosylation, leading to protein misfolding and deficiency.", "protein": "SERPINA1 (Alpha-1 antitrypsin)", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "N-glycosylation impacts CFTR folding and trafficking.", "mechanism": "Mutations in CFTR affect glycosylation and channel function.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "medium", "disease": "Phenylketonuria", "glycan_involvement": "Glycosylation may affect PAH stability and activity.", "mechanism": "Mutations in PAH disrupt enzyme activity.", "protein": "PAH (Phenylalanine hydroxylase)", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "medium", "disease": "Stargardt disease", "glycan_involvement": "ABCA4 is glycosylated; glycosylation may affect protein folding.", "mechanism": "Mutations in ABCA4 impair retinal function.", "protein": "ABCA4", "protein_enriched": { "function": "Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) ", "gene_name": "ABCA4", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G22768VO", "G49108TO" ], "uniprot_id": "P78363" }, "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "medium", "disease": "Lethal congenital contracture syndrome 11", "glycan_involvement": "GLDN is a glycoprotein; glycosylation may be important for its function.", "mechanism": "Mutation in GLDN disrupts neuromuscular junction formation.", "protein": "GLDN (Gliomedin)", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "medium", "disease": "Fanconi anemia", "glycan_involvement": "FANCA is a glycoprotein; glycosylation may affect protein stability.", "mechanism": "Mutations in FANCA impair DNA repair, leading to anemia and cancer risk.", "protein": "FANCA", "relationship_type": "causal", "source_pmcid": "PMC6778823" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Mac-1 is a glycoprotein; glycosylation is essential for its surface expression and ligand binding.", "mechanism": "Activated Mac-1 on neutrophils increases adhesion to endothelium and promotes NET release in APS.", "protein": "Integrin Mac-1 (CD11b/CD18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6798700" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "ICAM-1 is heavily glycosylated, which modulates its adhesive properties.", "mechanism": "ICAM-1 on endothelial cells interacts with Mac-1, facilitating neutrophil adhesion in APS.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC6798700" }, { "confidence": "medium", "disease": "Venous Thrombosis", "glycan_involvement": "Glycosylation of Mac-1 affects its activation and interaction with ICAM-1.", "mechanism": "Enhanced Mac-1-mediated neutrophil adhesion and NET release may contribute to thrombosis in APS.", "protein": "Integrin Mac-1 (CD11b/CD18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC6798700" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Antibody binding may be influenced by glycosylation state of Mac-1.", "mechanism": "Blocking Mac-1 with monoclonal antibody reduces neutrophil adhesion and NET release.", "protein": "Integrin Mac-1 (CD11b/CD18)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6798700" }, { "confidence": "medium", "disease": "Venous Thrombosis", "glycan_involvement": "Glycosylation regulates ICAM-1's binding affinity for integrins.", "mechanism": "ICAM-1 engagement by Mac-1 promotes neutrophil-endothelium interaction, contributing to thrombosis.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC6798700" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "Glycosylation may affect ALT stability and serum levels.", "mechanism": "ALT levels are used in the Hepatic Steatosis Index (HSI) to assess liver fat accumulation.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "medium", "disease": "Hepatic Steatosis", "glycan_involvement": "Glycosylation may affect AST stability and serum levels.", "mechanism": "AST levels are used in the HSI to assess hepatic steatosis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "low", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation may modulate ALT's serum half-life and detection.", "mechanism": "HSI (using ALT) is correlated with ASCVD risk score, suggesting ALT as an indirect biomarker for ASCVD risk.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "low", "disease": "Atherosclerotic Cardiovascular Disease (ASCVD)", "glycan_involvement": "Glycosylation may modulate AST's serum half-life and detection.", "mechanism": "HSI (using AST) is correlated with ASCVD risk score, suggesting AST as an indirect biomarker for ASCVD risk.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "low", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect ALT's activity in metabolic contexts.", "mechanism": "HSI includes diabetes status (+2), indicating ALT's role in metabolic disease assessment.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "low", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation may affect AST's activity in metabolic contexts.", "mechanism": "HSI includes diabetes status (+2), indicating AST's role in metabolic disease assessment.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC6809935" }, { "confidence": "high", "disease": "Alzheimer\u2019s disease", "glycan_involvement": "APOE is a glycoprotein; glycosylation may affect its lipid transport and neuronal functions.", "mechanism": "APOE4 allele increases risk of Alzheimer\u2019s disease; APOE2 allele is protective.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal", "source_pmcid": "PMC6841449" }, { "confidence": "high", "disease": "Cognitive decline", "glycan_involvement": "Glycosylation of APOE may modulate its neuroprotective functions.", "mechanism": "Homozygous APOE2 carriers show significantly slower cognitive decline compared to other genotypes.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective", "source_pmcid": "PMC6841449" }, { "confidence": "high", "disease": "Longevity", "glycan_involvement": "Glycosylation may influence APOE stability and function in aging.", "mechanism": "APOE2 allele is strongly associated with increased human longevity.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "protective", "source_pmcid": "PMC6841449" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects APOE structure and receptor interactions.", "mechanism": "APOE e_2 allele is neuroprotective and associated with reduced risk of late onset Alzheimer's disease.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "causal/protective", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates CLU stability and function.", "mechanism": "CLU levels correlate with APOE genotype and Alzheimer's risk.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation regulates C3 activation and immune response.", "mechanism": "C3 tracks with APOE genotype and is altered in AD brain.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects A2M protease inhibition.", "mechanism": "A2M levels associate with APOE genotype and cognitive function.", "protein": "Alpha-2-macroglobulin (A2M)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation modulates HP antioxidant activity.", "mechanism": "HP correlates with cognitive function changes in centenarians.", "protein": "Haptoglobin (HP)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation influences iron binding and transport.", "mechanism": "TF levels track with APOE genotype and AD status.", "protein": "Serotransferrin (TF)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation regulate APP cleavage and aggregation.", "mechanism": "APP processing and glycosylation affect amyloid-beta production.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation modulates IGF binding.", "mechanism": "IGFBP2 levels associate with cognitive function and APOE genotype.", "protein": "IGFBP2", "protein_enriched": { "function": "Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proli", "gene_name": "IGFBP2", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G43417UB", "G57321FI", "G49108TO" ], "uniprot_id": "P18065" }, "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Longevity", "glycan_involvement": "N- and O-glycosylation affect FN1 cell adhesion.", "mechanism": "FN1 tracks with APOE e_2 and increased longevity.", "protein": "Fibronectin (FN1)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates VTN interaction with amyloid.", "mechanism": "VTN levels correlate with APOE genotype and AD risk.", "protein": "Vitronectin (VTN)", "relationship_type": "biomarker", "source_pmcid": "PMC6841567" }, { "confidence": "high", "disease": "Intracerebral Hemorrhage (ICH)", "glycan_involvement": "MMP-9 is a glycoprotein; glycosylation may affect its secretion and activity, but not directly discussed in this article.", "mechanism": "MMP-9 contributes to extracellular matrix remodeling, blood-brain barrier (BBB) degradation, and vessel wall breakdown, increasing ICH risk.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC6849403" }, { "confidence": "high", "disease": "Intracerebral Hemorrhage (ICH)", "glycan_involvement": "Glycosylation may influence MMP-9 stability and serum levels, but not directly discussed in this article.", "mechanism": "Elevated serum MMP-9 levels are associated with ICH and increased mortality.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "biomarker", "source_pmcid": "PMC6849403" }, { "confidence": "high", "disease": "Nipah encephalitis", "glycan_involvement": "Glycosylation of G is essential for receptor binding and immune evasion.", "mechanism": "Glycoprotein G mediates viral attachment to host cells via ephrin-B2/B3 receptors, initiating infection.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "causal", "source_pmcid": "PMC6849404" }, { "confidence": "high", "disease": "Nipah encephalitis", "glycan_involvement": "N-glycosylation of F is critical for proper folding and fusion activity.", "mechanism": "Glycoprotein F facilitates membrane fusion between virus and host cell, enabling viral entry.", "protein": "Nipah virus glycoprotein F", "relationship_type": "causal", "source_pmcid": "PMC6849404" }, { "confidence": "medium", "disease": "Microinfarcts (neurological complication)", "glycan_involvement": "Glycosylation modulates tropism and immune escape, exacerbating vascular pathology.", "mechanism": "Viral entry via G leads to endothelial infection, contributing to microvascular damage and infarcts.", "protein": "Nipah virus glycoprotein G", "protein_enriched": { "function": "Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During ", "gene_name": "F", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9IH63" }, "relationship_type": "causal", "source_pmcid": "PMC6849404" }, { "confidence": "high", "disease": "Atypical Hemolytic Uremic Syndrome", "glycan_involvement": "Glycosylation affects Factor B stability and function.", "mechanism": "Mutation in Factor B gene leads to dysregulation of alternative complement pathway, causing endothelial injury and microangiopathy.", "protein": "Complement Factor B", "relationship_type": "causal", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation required for NGAL secretion and stability.", "mechanism": "Urinary NGAL levels correlate with CKD progression.", "protein": "Neutrophil Gelatinase-Associated Lipocalin (NGAL)", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease", "glycan_involvement": "N-glycosylation modulates P-glycoprotein trafficking and drug efflux.", "mechanism": "Metformin reduces P-glycoprotein expression, enhancing corticosteroid anti-inflammatory effects.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Infection-related Glomerulonephritis", "glycan_involvement": "Glycosylation regulates CD64 ligand binding and immune signaling.", "mechanism": "Neutrophil CD64 expression differentiates infection from non-infection states.", "protein": "CD64 (Fc gamma receptor I)", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "O-glycosylation required for FGF23 secretion.", "mechanism": "FGF23 levels increase in CKD, associated with mineral bone disorder.", "protein": "Fibroblast Growth Factor 23 (FGF23)", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "N-glycosylation essential for Klotho stability and function.", "mechanism": "Klotho deficiency contributes to CKD progression and vascular calcification.", "protein": "Klotho", "protein_enriched": { "function": "May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in viv", "gene_name": "KL", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G43417UB", "G41071NU", "G47448YK", "G62765YT", "G80920RR", "G83460ZZ", "G87661QW" ], "uniprot_id": "Q9UEF7" }, "relationship_type": "protective", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation modulates C1q immune complex formation.", "mechanism": "Anti-C1q antibodies correlate with disease activity and renal involvement.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation affects C3 activation and complement cascade.", "mechanism": "Low serum C3 indicates active lupus nephritis.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation required for C4 function in complement activation.", "mechanism": "Low serum C4 is associated with lupus nephritis activity.", "protein": "C4", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Lupus Nephritis", "glycan_involvement": "Glycosylation of IgG modulates antibody effector function.", "mechanism": "Anti-dsDNA antibody levels correlate with lupus nephritis severity.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC6883483" }, { "confidence": "high", "disease": "Idiopathic Nephrotic Syndrome", "glycan_involvement": "Glycosylation affects protein stability and drug transport.", "mechanism": "Altered expression/function identifies steroid resistance phenotype.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "high", "disease": "Idiopathic Nephrotic Syndrome", "glycan_involvement": "Glycosylation modulates transporter activity.", "mechanism": "Expression/function and SNPs (G2677T/A) linked to steroid resistance.", "protein": "Multidrug Resistance-Associated Protein-1 (MRP1)", "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "high", "disease": "IgA Nephropathy", "glycan_involvement": "O-glycosylation defects in IgA1 hinge region.", "mechanism": "Aberrant IgA glycosylation leads to immune complex deposition in glomeruli.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Renal Transplant Rejection", "glycan_involvement": "Glycosylation regulates enzyme activity and localization.", "mechanism": "Genetic predisposition and altered MMP activity associated with allograft rejection.", "protein": "Matrix Metalloproteinases (MMPs)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Renal Transplant Rejection", "glycan_involvement": "Glycosylation affects TIMP stability.", "mechanism": "Balance of TIMPs and MMPs influences rejection risk.", "protein": "Tissue Inhibitors of Metalloproteinases (TIMPs)", "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Membranous Nephropathy", "glycan_involvement": "Altered glycosylation impacts immune complex formation.", "mechanism": "IgA levels and glycosylation status may influence disease course.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Renal Transplant Rejection", "glycan_involvement": "Glycosylation modulates drug binding and efflux.", "mechanism": "Pharmacogenomic variation affects immunosuppressant dosing.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Renal Transplant Rejection", "glycan_involvement": "Glycosylation affects transporter function.", "mechanism": "Genetic and glycosylation status influence drug resistance.", "protein": "Multidrug Resistance-Associated Protein-1 (MRP1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC6883486" }, { "confidence": "medium", "disease": "Infection-Related Glomerulonephritis", "glycan_involvement": "Glycosylation status influences immune response.", "mechanism": "IgA deposition in glomeruli linked to infection-related pathology.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "low", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation impacts protein localization and function.", "mechanism": "Expression levels may affect drug handling and disease progression.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "biomarker", "source_pmcid": "PMC6883486" }, { "confidence": "high", "disease": "Microalbuminuria", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect its filtration and detection.", "mechanism": "Elevated urinary albumin indicates glomerular damage in early diabetic nephropathy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC6892323" }, { "confidence": "high", "disease": "Diabetic nephropathy", "glycan_involvement": "Glycosylation status may influence albumin's renal handling.", "mechanism": "Urinary albumin excretion reflects progression of diabetic nephropathy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC6892323" }, { "confidence": "medium", "disease": "Neuroblastoma", "glycan_involvement": "Not directly discussed in this article.", "mechanism": "MYCN amplification is associated with aggressive neuroblastoma and poor prognosis.", "protein": "MYCN", "relationship_type": "biomarker", "source_pmcid": "PMC6894385" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 receptor binding.", "protein": "Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7080055" }, { "confidence": "high", "disease": "Viral infection", "glycan_involvement": "Glycan shield affects antibody accessibility.", "mechanism": "Targeting glycosylation sites on spike protein can inhibit viral infectivity.", "protein": "Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7080055" }, { "confidence": "medium", "disease": "Viral infection", "glycan_involvement": "Glycosylation may regulate RRF stability and function.", "mechanism": "RRF facilitates ribosome recycling, potentially limiting viral protein synthesis.", "protein": "Ribosome Recycling Factor (RRF)", "relationship_type": "protective", "source_pmcid": "PMC7080055" }, { "confidence": "medium", "disease": "Neurotoxicity", "glycan_involvement": "Glycosylation influences peptide stability and bioactivity.", "mechanism": "Apamin blocks SK channels, leading to neurotoxic effects.", "protein": "Apamin", "protein_enriched": { "function": "Melittin: Main toxin of bee venom with strong antimicrobial activity and hemolytic activity (PubMed:24512991, PubMed:4057243, PubMed:5139482, PubMed:5794226). It has enhancing effects on bee venom pho", "gene_name": "MELT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01501" }, "relationship_type": "causal", "source_pmcid": "PMC7080055" }, { "confidence": "low", "disease": "Viral infection", "glycan_involvement": "N-glycosylation changes affect protein function.", "mechanism": "Altered glycosylation patterns may indicate infection status.", "protein": "Reaction Center Protein", "relationship_type": "biomarker", "source_pmcid": "PMC7080055" }, { "confidence": "high", "disease": "West Nile Virus infection", "glycan_involvement": "N-glycosylation of E protein is essential for infectivity and neuroinvasion", "mechanism": "Mediates viral entry into host cells", "protein": "Envelope glycoprotein (E protein)", "relationship_type": "causal", "source_pmcid": "PMC7095058" }, { "confidence": "high", "disease": "Japanese Encephalitis", "glycan_involvement": "N-glycosylation modulates neurotropism and immune evasion", "mechanism": "Facilitates viral attachment and entry into neural cells", "protein": "Envelope glycoprotein (E protein)", "relationship_type": "causal", "source_pmcid": "PMC7095058" }, { "confidence": "medium", "disease": "West Nile Virus infection", "glycan_involvement": "Glycosylation required for secretion and immune modulation", "mechanism": "Secreted NS1 detected in serum during infection", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7095058" }, { "confidence": "medium", "disease": "Japanese Encephalitis", "glycan_involvement": "Glycosylation affects stability and immune recognition", "mechanism": "NS1 presence correlates with disease progression", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7095058" }, { "confidence": "high", "disease": "Carotid artery atherosclerosis", "glycan_involvement": "LRP6 is glycosylated; glycosylation may affect receptor function and stability.", "mechanism": "LRP6 1062V variant reduces LRP6 expression in plaques, increasing risk of atherosclerosis in hypertensive patients.", "protein": "LDL Receptor-Related Protein 6 (LRP6)", "relationship_type": "causal", "source_pmcid": "PMC7101653" }, { "confidence": "high", "disease": "Carotid artery atherosclerosis", "glycan_involvement": "Glycosylation affects fibrinogen's solubility and function in coagulation.", "mechanism": "Elevated plasma fibrinogen correlates with increased carotid intima-media thickness (IMT), indicating vascular damage.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "high", "disease": "Carotid artery atherosclerosis", "glycan_involvement": "D-dimer is a glycosylated fragment; glycosylation influences clearance.", "mechanism": "Elevated D-dimer independently associated with increased IMT and carotid artery disease.", "protein": "Fibrin D-dimer", "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Carotid artery atherosclerosis", "glycan_involvement": "CRP glycosylation modulates its immune activity.", "mechanism": "CRP levels correlate with IMT, reflecting vascular inflammation.", "protein": "C-Reactive Protein (CRP)", "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation affects chemokine stability and receptor binding.", "mechanism": "Serum IP-10 levels correlate with cardiovascular risk and hypertension, especially in postmenopausal women.", "protein": "Interferon Inducible Protein-10 (IP-10/CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "PAI-1 glycosylation regulates secretion and inhibitory activity.", "mechanism": "PAI-1 expression and plasma levels are increased in hypertensive patients, promoting a pro-thrombotic state.", "protein": "Plasminogen Activator Inhibitor-1 (PAI-1)", "protein_enriched": { "function": "Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it", "gene_name": "SERPINE1", "glycan_count": 16, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G07799LX", "G11870QZ", "G22310AV", "G26330YA", "G27058EU", "G45395BF", "G49955PK", "G51413EV", "G72791KH", "G84452RH", "G88374WZ", "G20706XG", "G92135MA", "G29068FM", "G43417UB", "G49108TO" ], "uniprot_id": "P05121" }, "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects TIMP1 stability and inhibitory function.", "mechanism": "Reduced TIMP1 expression in adipose tissue of hypertensive patients may contribute to vascular remodeling.", "protein": "Tissue Inhibitor of Metalloproteinases 1 (TIMP1)", "relationship_type": "biomarker", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Adiponectin glycosylation is essential for multimerization and activity.", "mechanism": "Low salt intake decreases plasma adiponectin, potentially reducing its anti-inflammatory and cardiovascular protective effects.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Amyloidosis (Apolipoprotein A-I)", "glycan_involvement": "Glycosylation may influence amyloidogenicity and plasma clearance.", "mechanism": "Leu75Pro mutation causes amyloid deposition in tissues; may have protective effect on carotid atherosclerosis.", "protein": "Apolipoprotein A-I", "relationship_type": "causal", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Vascular damage", "glycan_involvement": "Glycosylation may affect FLAP membrane localization and function.", "mechanism": "Genetic variants in FLAP modulate leukotriene synthesis and interact with smoking to increase vascular inflammation and damage.", "protein": "5-Lipoxygenase-Activating Protein (FLAP)", "relationship_type": "causal", "source_pmcid": "PMC7101653" }, { "confidence": "medium", "disease": "Non-Hodgkin lymphoma", "glycan_involvement": "Fc glycosylation modulates antibody-receptor interaction", "mechanism": "Fcgamma receptor polymorphism predicts response to rituximab therapy", "protein": "Fc gamma receptor (Fcgamma)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Immune thrombocytopenia", "glycan_involvement": "Glycosylation of IgG Fc region critical for anti-inflammatory effect", "mechanism": "IVIG used to treat immune-mediated thrombocytopenia", "protein": "Immunoglobulin (IVIG)", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Anemia (chronic renal failure)", "glycan_involvement": "N-glycosylation required for stability and activity", "mechanism": "Erythropoietin stimulates erythropoiesis in renal anemia", "protein": "Erythropoietin", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Anemia (chronic renal failure)", "glycan_involvement": "Additional N-glycans prolong serum half-life", "mechanism": "Darbepoetin alfa is a hyperglycosylated erythropoietin analog with increased half-life", "protein": "Darbepoetin alfa", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "medium", "disease": "Rh(D)-incompatible platelet transfusion", "glycan_involvement": "Fc glycosylation affects effector function", "mechanism": "Prevents alloimmunization in Rh(D)-negative patients", "protein": "Anti-D immunoglobulin", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "medium", "disease": "Severe sepsis", "glycan_involvement": "N-glycosylation required for activity and stability", "mechanism": "Used to control bleeding in severe sepsis", "protein": "Recombinant activated factor VII (rFVIIa)", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Fc glycosylation modulates ADCC", "mechanism": "Monoclonal antibody targeting HER2 in breast cancer", "protein": "Trastuzumab", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Fc glycosylation modulates effector function", "mechanism": "Targets CD20+ B cells in autoimmune disease", "protein": "Rituximab", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "medium", "disease": "Immune neonatal thrombopenia", "glycan_involvement": "Fc glycosylation essential for anti-inflammatory action", "mechanism": "IVIG used to treat neonatal thrombocytopenia", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "medium", "disease": "AIDS", "glycan_involvement": "Altered glycosylation of viral envelope proteins", "mechanism": "Inhibit HIV-1 protease, affecting viral glycoprotein processing", "protein": "Protease inhibitors (HIV-1)", "relationship_type": "therapeutic", "source_pmcid": "PMC7102062" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Altered O-glycosylation increases immunogenicity.", "mechanism": "Aberrant glycosylation exposes tumor-associated epitopes.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Sialyl Lewis X glycan required for binding.", "mechanism": "Mediates leukocyte rolling via glycan ligands.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "Autoimmune disease", "glycan_involvement": "Reduced galactosylation increases inflammation.", "mechanism": "Altered Fc glycosylation modulates immune effector functions.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Altered N-glycosylation pattern.", "mechanism": "Carbohydrate-deficient transferrin indicates liver dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Increased fucosylation in cancer.", "mechanism": "AFP glycoforms distinguish cancer from benign liver disease.", "protein": "Alpha-fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC7108591" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Changes in N-glycan branching.", "mechanism": "Altered glycosylation improves diagnostic specificity.", "protein": "PSA (Prostate Specific Antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC7108591" }, { "confidence": "medium", "disease": "Metastasis", "glycan_involvement": "O-glycosylation affects hyaluronan binding.", "mechanism": "Glycosylation modulates cell adhesion and migration.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7108591" }, { "confidence": "medium", "disease": "Metastasis", "glycan_involvement": "N-glycosylation controls cell motility.", "mechanism": "Glycosylation regulates integrin-mediated signaling.", "protein": "Integrin beta-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7108591" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation affects cleavage by secretases.", "mechanism": "Glycosylation influences APP processing and amyloid formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "N-glycosylation at multiple sites.", "mechanism": "Glycosylation required for EPO stability and activity.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7108591" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp41 is a glycoprotein; glycosylation modulates immune evasion and fusion efficiency.", "mechanism": "Mediates viral-host membrane fusion via basic-aromatic cluster and CRAC motif, facilitating viral entry.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7112282" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Hemagglutinin is heavily glycosylated, affecting receptor binding and immune recognition.", "mechanism": "Fusion peptide and juxtamembrane basic-aromatic cluster disrupt host membrane for viral entry.", "protein": "Influenza Hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7112282" }, { "confidence": "high", "disease": "Bacterial infection", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Antimicrobial peptide disrupts bacterial membranes via \u03b2-hairpin structure with basic-aromatic clusters.", "protein": "Protegrin-1", "relationship_type": "protective", "source_pmcid": "PMC7112282" }, { "confidence": "medium", "disease": "Cancer (signal transduction dysregulation)", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Regulates PI(4,5)P2 microdomains and cell signaling; dysregulation implicated in cancer.", "protein": "MARCKS", "protein_enriched": { "function": "Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/o", "gene_name": "MARCKS", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29966" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7112282" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "NMDA receptor is glycosylated; glycosylation affects trafficking and function.", "mechanism": "Juxtamembrane basic-aromatic clusters regulate channel closure and PI(4,5)P2 sequestration, affecting synaptic signaling.", "protein": "NMDA Receptor", "relationship_type": "causal", "source_pmcid": "PMC7112282" }, { "confidence": "medium", "disease": "Cancer (signal transduction dysregulation)", "glycan_involvement": "Caveolin is not a classical glycoprotein; minimal glycan involvement.", "mechanism": "Scaffolding domain (basic-aromatic cluster) organizes cholesterol-rich caveolae, modulating signaling pathways.", "protein": "Caveolin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7112282" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Juxtamembrane basic-aromatic cluster mediates synaptic vesicle fusion, essential for neurotransmission.", "protein": "Synaptobrevin (VAMP2)", "relationship_type": "causal", "source_pmcid": "PMC7112282" }, { "confidence": "low", "disease": "Neurological disorders", "glycan_involvement": "SCAMPs may be glycosylated; glycosylation could affect trafficking.", "mechanism": "Basic-aromatic clusters in SCAMPs facilitate membrane fusion during exocytosis.", "protein": "SCAMP", "relationship_type": "causal", "source_pmcid": "PMC7112282" }, { "confidence": "medium", "disease": "Cancer (signal transduction dysregulation)", "glycan_involvement": "PKC is not a glycoprotein; no glycan involvement.", "mechanism": "Basic-aromatic clusters mediate membrane binding and activation of PKC, a key signaling molecule in cancer.", "protein": "C1/C2 domains of Protein Kinase C", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7112282" }, { "confidence": "low", "disease": "Cancer (signal transduction dysregulation)", "glycan_involvement": "Not glycoproteins; no glycan involvement.", "mechanism": "Basic-aromatic clusters mediate PI(3)P binding and membrane targeting, affecting signaling pathways.", "protein": "FYVE domain proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7112282" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "NA is a glycoprotein; glycosylation affects function and inhibitor binding.", "mechanism": "NA is essential for viral release; inhibitors block viral spread.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA is a glycoprotein; glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry by binding to host sialic acids.", "protein": "Haemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "HIV/AIDS and related retroviral infections", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes from immune recognition.", "mechanism": "Envelope glycoproteins mediate viral entry and are targets for neutralizing antibodies.", "protein": "Envelope glycoproteins (HERV, HIV, HTLV, SIV, MLV)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "PR is essential for viral maturation; inhibitors block viral replication.", "protein": "HIV Protease (PR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "RT is essential for viral genome replication; inhibitors block viral replication.", "protein": "HIV Reverse Transcriptase (RT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "IN integrates viral DNA into host genome; inhibitors block integration.", "protein": "HIV Integrase (IN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "Hepatitis C (HCV)", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "NS3/4A protease is essential for viral polyprotein processing.", "protein": "HCV NS3/4A Protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7114997" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma (HCC)", "glycan_involvement": "Pre-S region is part of HBV surface glycoprotein; glycosylation may affect immune recognition and pathogenicity.", "mechanism": "Pre-S deletions are associated with progression from chronic hepatitis B to HCC.", "protein": "HBV pre-S region protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7114997" }, { "confidence": "medium", "disease": "Chronic Hepatitis B (CHB)", "glycan_involvement": "Pre-S region is glycosylated; glycan changes may influence disease progression.", "mechanism": "Pre-S region sequence patterns distinguish CHB from HCC.", "protein": "HBV pre-S region protein", "relationship_type": "biomarker", "source_pmcid": "PMC7114997" }, { "confidence": "medium", "disease": "HIV/AIDS and related retroviral infections", "glycan_involvement": "Glycosylation patterns influence membrane localization and immune evasion.", "mechanism": "Transmembrane regions in envelope glycoproteins are used for viral classification and prediction.", "protein": "Envelope glycoproteins (HERV, HIV, HTLV, SIV, MLV)", "relationship_type": "biomarker", "source_pmcid": "PMC7114997" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects APOE structure and function, influencing disease risk.", "mechanism": "APOE genotype is a major risk factor and biomarker for Alzheimer's disease.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC7115027" }, { "confidence": "high", "disease": "Dementia", "glycan_involvement": "Glycosylation modulates APOE interactions in the CNS.", "mechanism": "APOE variants are associated with increased risk of dementia.", "protein": "Apolipoprotein E (APOE)", "relationship_type": "biomarker", "source_pmcid": "PMC7115027" }, { "confidence": "high", "disease": "Adverse Drug Reactions (ADRs)", "glycan_involvement": "Glycosylation affects CYP2D6 stability and localization.", "mechanism": "CYP2D6 polymorphisms alter metabolism of psychotropic drugs, leading to ADRs.", "protein": "Cytochrome P450 2D6 (CYP2D6)", "relationship_type": "biomarker", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "CYP2D6 metabolizes antidepressants; genetic variants affect drug response.", "protein": "Cytochrome P450 2D6 (CYP2D6)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation may affect drug binding.", "mechanism": "CYP2D6 metabolizes neuroleptics; polymorphisms impact efficacy and safety.", "protein": "Cytochrome P450 2D6 (CYP2D6)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation may regulate enzyme function.", "mechanism": "CYP1A2 metabolizes neuroleptics; genetic variation influences drug response.", "protein": "Cytochrome P450 1A2 (CYP1A2)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, Pu", "gene_name": "CYP1A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05177" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "CYP1A2 metabolizes antidepressants; variants affect efficacy.", "protein": "Cytochrome P450 1A2 (CYP1A2)", "protein_enriched": { "function": "A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, Pu", "gene_name": "CYP1A2", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05177" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may affect enzyme stability.", "mechanism": "CYP2C19 metabolizes antidepressants; polymorphisms impact drug metabolism.", "protein": "Cytochrome P450 2C19 (CYP2C19)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "Glycosylation may regulate enzyme function.", "mechanism": "CYP3A4 metabolizes neuroleptics; genetic variation influences drug response.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation may modulate activity.", "mechanism": "CYP3A4 metabolizes antidepressants; variants affect efficacy.", "protein": "Cytochrome P450 3A4 (CYP3A4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7115027" }, { "confidence": "high", "disease": "Creutzfeldt\u2013Jakob disease", "glycan_involvement": "Glycosylation affects prion protein folding and pathogenicity.", "mechanism": "Misfolded glycoprotein aggregates cause neurodegeneration.", "protein": "Prion protein (PrPSc)", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Scrapie", "glycan_involvement": "Glycosylation modulates prion infectivity and strain properties.", "mechanism": "PrPSc accumulation in neural tissue leads to disease.", "protein": "Prion protein (PrPSc)", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Bovine spongiform encephalopathy", "glycan_involvement": "Glycosylation influences prion conversion and spread.", "mechanism": "PrPSc aggregates disrupt neural function.", "protein": "Prion protein (PrPSc)", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Herpes simplex infection", "glycan_involvement": "N-glycosylation critical for host cell recognition and immune modulation.", "mechanism": "Glycoproteins mediate viral entry and immune evasion.", "protein": "Herpesvirus envelope glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "medium", "disease": "Adenovirus respiratory disease", "glycan_involvement": "Glycosylation modulates tropism and immune response.", "mechanism": "Glycoproteins facilitate host cell attachment and infection.", "protein": "Adenovirus structural glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "medium", "disease": "Hepatitis D", "glycan_involvement": "Glycosylation essential for assembly and host interaction.", "mechanism": "Envelope glycoproteins required for viroid infectivity.", "protein": "Hepatitis D viroid-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "medium", "disease": "Poliomyelitis", "glycan_involvement": "Glycosylation affects antigenicity and host range.", "mechanism": "Capsid glycoproteins mediate cell entry and immune response.", "protein": "Picornavirus capsid glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Herpes simplex infection", "glycan_involvement": "N-glycosylation modulates receptor binding.", "mechanism": "gD is essential for viral entry; target for antivirals.", "protein": "Herpes Simplex Virus glycoprotein D", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Herpes simplex infection", "glycan_involvement": "N-glycosylation affects fusion activity and immune recognition.", "mechanism": "gB mediates membrane fusion; target for neutralizing antibodies.", "protein": "Herpes Simplex Virus glycoprotein B", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7119911" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation determines neurotropism and immune escape.", "mechanism": "Envelope glycoproteins enable neuroinvasion.", "protein": "Viral envelope glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7119911" }, { "confidence": "high", "disease": "Hereditary spherocytosis", "glycan_involvement": "N-glycosylation at Asn642 affects protein stability and membrane localization.", "mechanism": "Mutations disrupt interaction with cytoskeletal proteins, leading to RBC fragility.", "protein": "Chloride\u2013bicarbonate anion exchanger (AE1/SLC4A1)", "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Renal tubular acidosis", "glycan_involvement": "Glycosylation affects subunit assembly and targeting.", "mechanism": "Mutation impairs proton export in renal intercalated cells, disrupting acid\u2013base homeostasis.", "protein": "V-type ATPase", "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Osteoporosis", "glycan_involvement": "Glycosylation modulates subunit function in bone cells.", "mechanism": "Defective acidification in osteoclasts impairs bone resorption.", "protein": "V-type ATPase", "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycosylation may affect targeting and activity.", "mechanism": "Cancer cells manipulate V-type ATPase for pH regulation and survival.", "protein": "V-type ATPase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation required for membrane insertion and stability.", "mechanism": "Targeted by digitalis glycosides and ouabain for heart failure treatment.", "protein": "Na+/K+ ATPase \u03b2-subunit", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7119958" }, { "confidence": "medium", "disease": "Muscle contraction disorders", "glycan_involvement": "Glycosylation influences folding and activity.", "mechanism": "Defective Ca2+ transport impairs muscle relaxation.", "protein": "SERCA (Sarcoplasmic Reticulum Ca2+ ATPase)", "protein_enriched": { "function": "Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coup", "gene_name": "ATP2A1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04191" }, "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Hypoglycemia", "glycan_involvement": "N-glycosylation in extracellular loop modulates transport efficiency.", "mechanism": "High-affinity glucose transport maintains cellular glucose even in low blood glucose.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "protective", "source_pmcid": "PMC7119958" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation affects transporter stability and localization.", "mechanism": "SGLT1 mediates intestinal glucose absorption; inhibitors used for glycemic control.", "protein": "SGLT1", "protein_enriched": { "function": "Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a tr", "gene_name": "SLC5A1", "glycan_count": 6, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G29068FM", "G43417UB", "G53434XO", "G57321FI", "G58001LT", "G49108TO" ], "uniprot_id": "P13866" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Hemolytic anemia", "glycan_involvement": "N-glycosylation at Asn642 critical for function.", "mechanism": "Defective anion exchange leads to RBC shape abnormalities and hemolysis.", "protein": "Chloride\u2013bicarbonate anion exchanger (AE1/SLC4A1)", "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Acid\u2013base imbalance", "glycan_involvement": "Glycosylation modulates pump density and activity.", "mechanism": "Impaired proton transport disrupts systemic pH regulation.", "protein": "V-type ATPase", "relationship_type": "causal", "source_pmcid": "PMC7119958" }, { "confidence": "high", "disease": "Severe Dengue (DHF/DSS)", "glycan_involvement": "Glycosylation affects epitope exposure and antibody binding, influencing ADE.", "mechanism": "Antibodies against E protein domains (EDI, EDII) mediate ADE, enhancing viral entry and replication, leading to severe disease.", "protein": "Dengue virus Envelope glycoprotein (E)", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "high", "disease": "Severe Dengue (DHF/DSS)", "glycan_involvement": "Glycosylation may affect prM processing and antibody recognition.", "mechanism": "Anti-prM antibodies enable infection of immature virions via ADE, contributing to severe dengue.", "protein": "Dengue virus Precursor membrane glycoprotein (prM)", "protein_enriched": { "function": "Rod linker protein, associated with phycocyanin (PC). Linker polypeptides determine the state of aggregation and the location of the disk-shaped phycobiliprotein units within the phycobilisome (PBS) a", "gene_name": "cpcL", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P29988" }, "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation modulates antigenicity and antibody binding.", "mechanism": "Antibodies to gp41 mediate complement-dependent ADE, enhancing viral entry and replication.", "protein": "HIV Envelope glycoprotein gp41", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense N-glycosylation shields epitopes, affects antibody access and ADE susceptibility.", "mechanism": "Antibodies to gp120 mediate FcR-independent ADE by modulating co-receptor interactions and fusion.", "protein": "HIV Envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation of HA modulates antigenicity and immune response.", "mechanism": "Anti-HA antibodies mediate ADE via FcR-dependent uptake and enhanced fusion.", "protein": "Influenza virus Hemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation affects NA structure and antibody recognition.", "mechanism": "Anti-NA antibodies facilitate FcR-mediated uptake, possibly contributing to ADE.", "protein": "Influenza virus Neuraminidase (NA)", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "Respiratory Syncytial Virus (RSV) disease", "glycan_involvement": "Glycosylation influences G protein immunogenicity and ADE risk.", "mechanism": "Anti-G antibodies mediate ADE via FcR-dependent uptake into immune cells.", "protein": "RSV Glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "Respiratory Syncytial Virus (RSV) disease", "glycan_involvement": "Glycosylation affects F protein folding and antibody binding.", "mechanism": "Anti-F antibodies mediate ADE via FcR-dependent uptake and immune modulation.", "protein": "RSV Fusion glycoprotein F", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "Ebola Virus Disease", "glycan_involvement": "Heavy glycosylation shields GP, modulates antibody access and ADE.", "mechanism": "Anti-GP antibodies promote ADE via FcR- or complement-mediated uptake into target cells.", "protein": "Ebola virus Glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "medium", "disease": "COVID-19/SARS", "glycan_involvement": "N-glycosylation of S protein affects epitope exposure and ADE risk.", "mechanism": "Anti-S antibodies mediate ADE via FcR-dependent uptake into immune cells.", "protein": "SARS-CoV Spike glycoprotein (S)", "relationship_type": "causal", "source_pmcid": "PMC7119964" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "O-glycosylation critical for mucin function and airway defense.", "mechanism": "Promoter SNP (rs35705950) increases MUC5B expression, conferring susceptibility and influencing progression and survival.", "protein": "MUC5B", "protein_enriched": { "function": "Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus", "gene_name": "MUC5B", "glycan_count": 47, "glycosylation_sites_count": 38, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G62765YT", "G80920RR", "G84452RH", "G48414YA", "G66760KM", "G57321FI", "G64527OM", "G39188ZX", "G31852PQ", "G70822IO", "G75983OB", "G05724UK", "G06110VR", "G10773YW", "G29880MM", "G46687AB", "G82119TF", "G02030ZB", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G40142JY", "G42665KV", "G49582PC", "G58272ZE", "G63110FE", "G63628AV", "G63760GT", "G64973KT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G78315FS", "G79243QP", "G81006GJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q9HC84" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Elevated CHI3L1 augments alternative macrophage activation (CD206+), tracks with fibrosis severity.", "protein": "CHI3L1 (YKL-40)", "protein_enriched": { "function": "Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure ", "gene_name": "Stk39", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9Z1W9" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7120022" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Binds mannose-rich glycans; glycosylation essential for ligand recognition.", "mechanism": "Increased CD206+ macrophages in IPF lungs, marker of alternative activation and fibrosis.", "protein": "CD206 (Mannose receptor)", "relationship_type": "biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Chemokine glycosylation affects stability and receptor binding.", "mechanism": "Plasma CXCL13 elevated in IPF, especially with PAH or acute exacerbations; predicts respiratory failure.", "protein": "CXCL13", "relationship_type": "biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "high", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation modulates chemokine activity.", "mechanism": "BALF CXCL8 correlates with neutrophil presence and worse prognosis in IPF.", "protein": "CXCL8 (IL-8)", "relationship_type": "biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation influences chemokine function.", "mechanism": "Elevated in IPF lung and blood; inhibits angiogenesis and may reflect Hedgehog pathway activity.", "protein": "CXCL14", "protein_enriched": { "function": "Potent chemoattractant for neutrophils, and weaker for dendritic cells. Not chemotactic for T-cells, B-cells, monocytes, natural killer cells or granulocytes. Does not inhibit proliferation of myeloid", "gene_name": "CXCL14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95715" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation may affect protein stability and trafficking.", "mechanism": "TOLLIP SNPs regulate gene expression, affecting TLR signaling and IPF susceptibility/mortality.", "protein": "TOLLIP", "protein_enriched": { "function": "Component of the signaling pathway of IL-1 and Toll-like receptors (PubMed:10854325, PubMed:11751856). Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex (PubM", "gene_name": "TOLLIP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9H0E2" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "Glycosylation may influence antigenicity.", "mechanism": "Autoantibodies against periplakin over-represented in IPF, linked to epithelial injury.", "protein": "Periplakin", "relationship_type": "autoantigen/biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "GP130 involved in IL-6 signaling downstream of hyaluronan-TLR4 axis, affecting AEC2 renewal.", "protein": "GP130 (IL6ST)", "relationship_type": "causal", "source_pmcid": "PMC7120022" }, { "confidence": "medium", "disease": "Idiopathic Pulmonary Fibrosis (IPF)", "glycan_involvement": "O-glycosylation essential for mucin barrier properties.", "mechanism": "Highly expressed in distal airways; may contribute to altered mucosal defense in IPF.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120022" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialic acid linkage determines host specificity; glycosylation shields antigenic sites.", "mechanism": "HA binds sialic acid on host cells, mediates entry and tropism.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavy N-glycosylation required for CD4 binding and shields from neutralizing antibodies.", "mechanism": "gp120 binds CD4 and HSPG, mediates viral entry and immune evasion.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "Attachment to HSPG is glycan-dependent and critical for tropism.", "mechanism": "HPV L1 binds HSPG, facilitating infection of epithelial cells.", "protein": "L1 major capsid protein", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "West Nile fever", "glycan_involvement": "N-glycosylation on E protein enhances entry and particle release.", "mechanism": "E protein glycosylation required for receptor binding, fusion, and pathogenicity.", "protein": "E protein (Flaviviruses)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation loss reduces viral entry.", "mechanism": "E1 glycosylation required for folding and cell surface translocation.", "protein": "E1 protein (HCV)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Herpes simplex infection", "glycan_involvement": "Sialic acid-dependent recognition critical for entry.", "mechanism": "gB binds PILR\u03b1 in a sialic acid-dependent manner, mediates membrane fusion.", "protein": "gB (HSV)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "medium", "disease": "AIDS encephalopathy", "glycan_involvement": "HSPG binding and oligomerization facilitate neurotoxicity.", "mechanism": "Tat interacts with HSPG, internalized and activates HIV gene transcription.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Polyomavirus-associated demyelinating disease", "glycan_involvement": "Specific sialic acid linkages determine tropism and pathogenicity.", "mechanism": "VP1 binds sialic acid-containing gangliosides, mediates cell entry.", "protein": "VP1 (Polyomaviruses)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "West Nile fever", "glycan_involvement": "N-glycosylation enhances infectivity.", "mechanism": "prM glycosylation required for viral entry and particle release.", "protein": "prM (Flaviviruses)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "High-mannose N-glycans facilitate liver/DC infection.", "mechanism": "E2 binds DC-SIGN/L-SIGN via high-mannose N-glycans, mediates infection.", "protein": "E2 protein (HCV)", "relationship_type": "causal", "source_pmcid": "PMC7120038" }, { "confidence": "high", "disease": "Autism Spectrum Disorder", "glycan_involvement": "APP is a glycoprotein; glycosylation affects its processing and secretion.", "mechanism": "Upregulation of non-amyloidogenic sAPP\u03b1 pathway associated with severe autism and self-injurious/aggressive behavior.", "protein": "Amyloid Precursor Protein (APP)", "relationship_type": "biomarker", "source_pmcid": "PMC7120060" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "Glycosylation modulates APP cleavage and aggregation.", "mechanism": "Amyloidogenic processing produces A\u03b2 peptides, leading to plaque formation and neurodegeneration.", "protein": "Amyloid Precursor Protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "N-glycosylation required for cell surface expression and function.", "mechanism": "Mutations disrupt synapse formation and neuronal connectivity.", "protein": "Neuroligin 3 (NLGN3)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "N-glycosylation essential for synaptic localization.", "mechanism": "Frameshift and deletion mutations linked to autism and related neuropsychiatric phenotypes.", "protein": "Neuroligin 4 (NLGN4X)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding.", "mechanism": "Mutations impair cell adhesion and synaptic differentiation.", "protein": "Neurexin 1 (NRXN1)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Glycosylation may affect protein-protein interactions at synapse.", "mechanism": "Mutations cause severe verbal and social deficits via postsynaptic scaffolding disruption.", "protein": "SHANK3", "protein_enriched": { "function": "Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects rec", "gene_name": "SHANK3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BYB0" }, "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Secreted glycoprotein; glycosylation required for secretion and function.", "mechanism": "Polymorphisms and deletions affect neuronal migration and cortical organization.", "protein": "RELN (Reelin)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "high", "disease": "Fragile X Syndrome", "glycan_involvement": "Glycosylation may regulate RNA-binding and protein stability.", "mechanism": "Loss of FMRP leads to synaptic dysfunction and autistic features.", "protein": "FMR1 (Fragile X Mental Retardation Protein)", "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "medium", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Semaphorins are glycoproteins; glycosylation affects axonal signaling.", "mechanism": "Downregulation in brain tissue and lymphocytes; involved in axonal guidance.", "protein": "SEMA5A", "protein_enriched": { "function": "Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on int", "gene_name": "SEMA5A", "glycan_count": 2, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G02815KT", "G80920RR" ], "uniprot_id": "Q13591" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120060" }, { "confidence": "low", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Glycosylation modulates cell adhesion and synaptic specificity.", "mechanism": "Missense mutations associated with autism and related neuropsychiatric traits.", "protein": "Neurexin 3 (NRXN3)", "protein_enriched": { "function": "Neuronal cell surface protein that may be involved in cell recognition and cell adhesion. May mediate intracellular signaling (By similarity)", "gene_name": "NRXN3", "glycan_count": 1, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G49018RC" ], "uniprot_id": "Q9Y4C0" }, "relationship_type": "causal", "source_pmcid": "PMC7120060" }, { "confidence": "high", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation required for proper folding and surface expression.", "mechanism": "Antigen presentation by microglia/macrophages drives T cell activation and CNS inflammation.", "protein": "MHC class II", "relationship_type": "causal", "source_pmcid": "PMC7120081" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "N-glycosylation critical for function.", "mechanism": "Essential for antigen presentation to CD4+ T cells in EAE.", "protein": "MHC class II", "relationship_type": "causal", "source_pmcid": "PMC7120081" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation modulates cell adhesion and migration.", "mechanism": "Marker of activated microglia/macrophages in lesions.", "protein": "CD11b (Integrin alpha-M)", "relationship_type": "biomarker", "source_pmcid": "PMC7120081" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Heavily glycosylated; glycan structure affects signaling.", "mechanism": "Expressed on infiltrating immune cells in MS lesions.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120081" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "N-glycosylation required for ligand binding.", "mechanism": "Facilitates leukocyte adhesion and transmigration into CNS.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120081" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis", "glycan_involvement": "Glycosylation affects surface expression and function.", "mechanism": "Co-stimulatory molecule for T cell activation by microglia/macrophages.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "causal", "source_pmcid": "PMC7120081" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APP is a glycoprotein; glycosylation affects trafficking and processing.", "mechanism": "Intrabodies targeting the \u03b2-secretase cleavage site of APP inhibit toxic A\u03b2 formation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Nicastrin glycosylation is essential for \u03b3-secretase complex stability.", "mechanism": "Anti-nicastrin intrabodies disrupt folding/glycosylation, suppressing \u03b3-secretase activity and A\u03b2 production.", "protein": "Nicastrin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Prion diseases", "glycan_involvement": "PrP glycosylation modulates trafficking and conversion to PrPSc.", "mechanism": "Intrabodies retain PrP in ER or reroute to proteasome, preventing pathogenic PrPSc formation.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes and affect infectivity.", "mechanism": "ER-retained intrabodies block gp120, inhibiting viral replication and syncytia formation.", "protein": "gp120 (HIV-1 envelope)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "gp41 is glycosylated, influencing envelope structure and immune evasion.", "mechanism": "Intrabodies against gp41 inhibit HIV-1 replication.", "protein": "gp41 (HIV-1 envelope)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Cancer (breast, ovary, colon)", "glycan_involvement": "EGFR glycosylation affects receptor folding, trafficking, and ligand binding.", "mechanism": "ER-retained intrabodies downregulate EGFR, inducing apoptosis and inhibiting proliferation.", "protein": "Epidermal growth factor receptor (EGFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Cancer (breast, ovary)", "glycan_involvement": "ErbB2 glycosylation is critical for receptor function and stability.", "mechanism": "ER-retained intrabodies reduce surface ErbB2, leading to apoptosis and tumor inhibition.", "protein": "ErbB2 (HER2/neu)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation of nicastrin is essential for its function.", "mechanism": "Proper glycosylation of nicastrin is required for \u03b3-secretase activity and A\u03b2 generation.", "protein": "Nicastrin", "relationship_type": "causal", "source_pmcid": "PMC7120103" }, { "confidence": "medium", "disease": "Prion diseases", "glycan_involvement": "N-glycosylation at two sites modulates PrP folding and disease susceptibility.", "mechanism": "Glycosylation state of PrP influences conversion to pathogenic PrPSc.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC7120103" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N- and O-glycosylation modulate APP trafficking and cleavage.", "mechanism": "Glycosylation affects APP processing and A\u03b2 peptide generation.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC7120103" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation (glycoside structure) critical for activity.", "mechanism": "Inhibits liver fibrosis and protects hepatocytes from bile acid-induced cytotoxicity.", "protein": "Glycyrrhizic acid (glycyrrhizin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Hepatitis (A, B, C)", "glycan_involvement": "Glycoside moiety essential for antiviral effect.", "mechanism": "Reduces serum ALT, necro-inflammation, and fibrosis; inhibits viral replication.", "protein": "Glycyrrhizic acid (glycyrrhizin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "Aglycone derived from glycoside; glycosylation affects bioactivity.", "mechanism": "Induces apoptosis and synergizes with anticancer drugs in multiple cancer cell lines.", "protein": "18\u03b2-Glycyrrhetinic acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "medium", "disease": "Neurodegenerative diseases (Alzheimer's, Parkinson's)", "glycan_involvement": "Glycoside structure may facilitate DNA binding and neuroprotective effects.", "mechanism": "Promotes neurite outgrowth and may protect against neurodegeneration.", "protein": "Liquiritin", "relationship_type": "protective", "source_pmcid": "PMC7120246" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation required for activity.", "mechanism": "Attenuates RAGE/NF\u03baB pathway activation by AGEs in endothelial cells.", "protein": "Liquiritin", "relationship_type": "protective", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Skin hyperpigmentation", "glycan_involvement": "No direct glycosylation, but interacts with glycoprotein enzymes.", "mechanism": "Inhibits tyrosinase, reduces UV-B-induced pigmentation and erythema.", "protein": "Glabridin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycoside structure modulates immune signaling.", "mechanism": "Inhibits proinflammatory cytokines, modulates PI3K and GR signaling.", "protein": "Glycyrrhizic acid (glycyrrhizin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "HMGB1 is a glycoprotein; glycyrrhizic acid binding modulates its function.", "mechanism": "Glycyrrhizic acid binds HMGB1, inhibiting its extracellular signaling in acute/chronic inflammation.", "protein": "High-mobility group box 1 (HMGB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120246" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Aglycone; glycosylation state affects bioactivity.", "mechanism": "Induces apoptosis, inhibits cell cycle, suppresses metastasis in multiple cancer models.", "protein": "Liquiritigenin", "relationship_type": "protective", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Gastric ulcer", "glycan_involvement": "Glycoside structure essential for antiulcer effect.", "mechanism": "Speeds healing of gastric ulcers and inhibits H. pylori growth.", "protein": "Glycyrrhizic acid (glycyrrhizin)", "relationship_type": "protective", "source_pmcid": "PMC7120246" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Reduced galactosylation and sialylation of IgG N-glycans increases pro-inflammatory activity.", "mechanism": "Altered glycosylation of IgG modulates immune complex formation and inflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Decreased galactosylation and sialylation of IgG N-glycans promote inflammation.", "mechanism": "IgG glycan changes correlate with disease activity and severity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "medium", "disease": "Mixed Cryoglobulinemia", "glycan_involvement": "Glycosylation affects solubility and immune complex formation.", "mechanism": "Cryoglobulins precipitate at low temperature, causing vasculitis.", "protein": "Cryoglobulin", "relationship_type": "causal", "source_pmcid": "PMC7120315" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation modulates C3 stability and function.", "mechanism": "C3 activation is central to the inflammatory response in sepsis.", "protein": "Complement component C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 98, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49955PK", "G69834CE", "G95678HJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10471FG", "G10486CT", "G11115RO", "G14260UH", "G14972EH", "G15664MX", "G17208MA", "G20312EM", "G23294PN", "G23453IV", "G23719VF", "G26330YA", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G32104JU", "G33609NS", "G34029GR", "G34730YF", "G36442WJ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G42124LM", "G46503DX", "G46691LC", "G48414YA", "G49018RC", "G50282JC", "G55220VL", "G57317CE", "G57776ZU", "G59626AS", "G60145BJ", "G61302NC", "G62765YT", "G63041LO", "G64527OM", "G65000LJ", "G65184UU", "G66538GV", "G66676MI", "G67324HN", "G68490OW", "G70101JE", "G70160EA", "G70441OD", "G70619PT", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G76295SF", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84349RE", "G87661QW", "G90575OW", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G96091TT", "G96430BV", "G99679NM", "G22768VO", "G30769VJ", "G31544HA", "G70375MX", "G72398FA", "G78790NZ", "G86234IN", "G90093AU", "G43417UB", "G40702WU", "G49108TO", "G68668TB", "G83161QT" ], "uniprot_id": "P01024" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects CRP's ligand binding and clearance.", "mechanism": "CRP is an acute phase reactant elevated in sepsis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "medium", "disease": "Fever of Unknown Origin (FUO)", "glycan_involvement": "N-glycosylation influences haptoglobin's anti-inflammatory properties.", "mechanism": "Haptoglobin is elevated in inflammatory states including FUO.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "medium", "disease": "Vasculitis", "glycan_involvement": "Glycosylation required for ligand binding and cell trafficking.", "mechanism": "E-selectin mediates leukocyte adhesion to endothelium in vasculitis.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC7120315" }, { "confidence": "low", "disease": "Endocarditis", "glycan_involvement": "O-glycosylation modulates MUC1's protective barrier function.", "mechanism": "MUC1 expression increases in inflamed endocardial tissue.", "protein": "Mucin-1 (MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC7120315" }, { "confidence": "low", "disease": "Necrotizing Fasciitis", "glycan_involvement": "N-glycosylation affects CD14's cell surface expression and LPS binding.", "mechanism": "CD14 mediates recognition of bacterial LPS, driving inflammation.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC7120315" }, { "confidence": "low", "disease": "Acute Rheumatic Fever", "glycan_involvement": "O-glycosylation provides steric hindrance to pathogen binding.", "mechanism": "Glycophorin A may limit bacterial adhesion to erythrocytes.", "protein": "Glycophorin A", "relationship_type": "protective", "source_pmcid": "PMC7120315" }, { "confidence": "high", "disease": "Cancer (breast cancer model)", "glycan_involvement": "Glycosylation of CD44 regulates cell adhesion and migration.", "mechanism": "CD44 mediates MSC homing to tumor stroma and vasculature.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7120558" }, { "confidence": "high", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation affects CD31-mediated cell-cell interactions.", "mechanism": "MSC-derived endothelial cells integrate into CD31+ vessels, promoting angiogenesis and cardiac repair.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Erectile dysfunction (corpus cavernosum injury)", "glycan_involvement": "vWF glycosylation is essential for its function in hemostasis and cell adhesion.", "mechanism": "MSC differentiation into endothelial cells marked by vWF expression aids tissue regeneration.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Chronic allograft rejection", "glycan_involvement": "Glycosylation modulates antigen presentation and immune recognition.", "mechanism": "Downregulation of MHC I/II glycoproteins reduces immune rejection of vascular grafts.", "protein": "HLA-DR1", "relationship_type": "therapeutic target", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Angiogenesis (wound healing, myocardial infarction)", "glycan_involvement": "Glycosylation influences CD105 function in TGF-beta signaling.", "mechanism": "CD105+ MSCs contribute to neovascularization and tissue repair.", "protein": "CD105 (Endoglin)", "relationship_type": "biomarker", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Wound healing/skin injury", "glycan_involvement": "IL10 glycosylation affects secretion and stability.", "mechanism": "MSC-mediated IL10 expression enhances tendon healing and reduces inflammation.", "protein": "IL10", "relationship_type": "therapeutic target", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Wound healing/skin injury", "glycan_involvement": "HGF glycosylation is required for receptor binding and activity.", "mechanism": "HGF secretion by MSCs promotes keratinocyte proliferation and re-epithelialization.", "protein": "Hepatocyte Growth Factor (HGF)", "relationship_type": "therapeutic target", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Dental tissue regeneration", "glycan_involvement": "Glycosylation modulates CD73 enzymatic activity.", "mechanism": "CD73+ MSCs are used for oral tissue regeneration and bone healing.", "protein": "CD73 (NT5E)", "relationship_type": "biomarker", "source_pmcid": "PMC7120558" }, { "confidence": "medium", "disease": "Ischemia-reperfusion injury", "glycan_involvement": "Not specified in article.", "mechanism": "Bcl-xL overexpression in endothelial cells protects against apoptosis during I/R injury.", "protein": "Bcl-xL", "relationship_type": "therapeutic target", "source_pmcid": "PMC7120558" }, { "confidence": "low", "disease": "Alzheimer's disease, Parkinson's disease", "glycan_involvement": "Glycosylation affects CD90 cell signaling and adhesion.", "mechanism": "CD90+ MSCs are used in research and therapy for neurodegenerative diseases.", "protein": "CD90 (Thy-1)", "protein_enriched": { "function": "May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain", "gene_name": "THY1", "glycan_count": 67, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G07246CJ", "G27058EU", "G41071NU", "G42124LM", "G77669RF", "G84452RH", "G90659AW", "G01160VV", "G02528FI", "G04657PL", "G05962QB", "G07755XJ", "G08918WF", "G16125XL", "G18647XP", "G20528HD", "G25079LO", "G27915IV", "G30970QQ", "G43223CG", "G45395BF", "G47644PP", "G57776ZS", "G59324HL", "G62765YT", "G63041LO", "G68490OW", "G70232NH", "G70441OD", "G72747WU", "G76295SF", "G79666IR", "G80075MS", "G80479JV", "G81637OR", "G85282JO", "G85554PZ", "G86182NS", "G87661QW", "G92135MA", "G93718GY", "G00912UN", "G01650EU", "G05049YU", "G06247RL", "G10819WX", "G13131HA", "G14972EH", "G23863VK", "G29545VG", "G31852PQ", "G35541EV", "G43669FQ", "G44437FL", "G49755GI", "G49906RN", "G60834IK", "G70619PT", "G71463BG", "G80920RR", "G83646BJ", "G86880BF", "G87123QX", "G95046LV", "G96091TT", "G98611JV", "G49108TO" ], "uniprot_id": "P04216" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120558" }, { "confidence": "high", "disease": "HIV-1 encephalitis (HIVE)", "glycan_involvement": "gp41 is heavily glycosylated, mediating immune evasion and cell entry", "mechanism": "gp41 detected by immunohistochemistry in multinucleated giant cells in brain tissue, indicating HIV-1 infection", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7120597" }, { "confidence": "high", "disease": "HIV-1 encephalitis (HIVE)", "glycan_involvement": "p24 is glycosylated, affecting antigenicity and immune recognition", "mechanism": "p24 detected in brain tissue by immunohistochemistry, confirming HIV-1 presence", "protein": "p24", "relationship_type": "biomarker", "source_pmcid": "PMC7120597" }, { "confidence": "high", "disease": "HIV-associated neurocognitive disorders (HAND)", "glycan_involvement": "CD4 glycosylation modulates HIV-1 binding and entry efficiency", "mechanism": "HIV-1 binds CD4 on T-cells and microglia/macrophages to enter CNS, leading to neurodegeneration", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "Rhinovirus infection (not CNS-specific)", "glycan_involvement": "ICAM-1 glycosylation affects viral binding", "mechanism": "ICAM-1 acts as receptor for rhinovirus entry into epithelial cells", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "high", "disease": "Influenza A virus infection", "glycan_involvement": "Sialylation of host glycoproteins is essential for viral attachment", "mechanism": "Influenza A virus binds sialic acid on epithelial cells for entry", "protein": "Sialic acid", "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "HVEM glycosylation influences HSV binding", "mechanism": "HSV uses HVEM as entry receptor on host cells, leading to CNS infection", "protein": "Herpesvirus entry mediator (HVEM)", "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "Herpes simplex encephalitis", "glycan_involvement": "Nectin 1 glycosylation modulates viral interaction", "mechanism": "HSV binds nectin 1 for cell entry, facilitating CNS infection", "protein": "Nectin 1", "protein_enriched": { "function": "Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignm", "gene_name": "INCENP", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G70232NH", "G49108TO" ], "uniprot_id": "Q9NQS7" }, "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "HIV-1 infection (vascular changes)", "glycan_involvement": "Glycosylation of vWF affects vascular integrity and immune response", "mechanism": "Reduced immunoreactivity for von Willebrand factor in HIV-1-infected brain vessels", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "HIV-1 leukoencephalopathy", "glycan_involvement": "Transferrin glycosylation impacts iron transport and immune modulation", "mechanism": "Increase in transferrin-immunopositive cells in white matter during myelin damage", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120597" }, { "confidence": "medium", "disease": "Epstein-Barr virus encephalitis", "glycan_involvement": "CD21 glycosylation modulates EBV binding", "mechanism": "EBV uses CD21 as entry receptor on B-cells, leading to CNS infection", "protein": "C3d complement receptor CR2 (CD21)", "relationship_type": "causal", "source_pmcid": "PMC7120597" }, { "confidence": "high", "disease": "Lysosomal storage diseases", "glycan_involvement": "Enzyme glycosylation is essential for lysosomal targeting and function.", "mechanism": "Mutations in glycoprotein lysosomal enzymes lead to substrate accumulation and disease.", "protein": "Lysosomal storage enzymes", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "high", "disease": "Feline leukemia", "glycan_involvement": "Glycosylation modulates immune evasion and infectivity.", "mechanism": "Viral glycoprotein mediates cell entry and oncogenesis.", "protein": "Feline leukemia virus envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "medium", "disease": "Feline sarcoma", "glycan_involvement": "Glycosylation affects receptor binding and pathogenicity.", "mechanism": "Viral glycoprotein facilitates transformation of host cells.", "protein": "Feline leukemia virus envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "high", "disease": "Feline immunodeficiency virus infection (FIV)", "glycan_involvement": "Glycosylation shields epitopes from immune detection.", "mechanism": "Envelope glycoprotein enables viral entry into T cells.", "protein": "Feline immunodeficiency virus (FIV) envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "Glycosylation influences host range and immune evasion.", "mechanism": "Spike glycoprotein mediates host cell entry and tropism.", "protein": "Feline coronavirus spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "medium", "disease": "Leukemia/lymphoma/sarcoma (Type C retrovirus-induced)", "glycan_involvement": "Glycosylation modulates infectivity and immune response.", "mechanism": "Envelope glycoprotein interacts with oncogenes to induce malignancy.", "protein": "Type C retrovirus envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120622" }, { "confidence": "high", "disease": "HER2-positive Breast Cancer", "glycan_involvement": "N-glycosylation modulates HER2 stability and antibody binding", "mechanism": "HER2 overexpression drives tumor growth; targeted by trastuzumab", "protein": "HER2/neu (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120678" }, { "confidence": "high", "disease": "HER2-positive Breast Cancer", "glycan_involvement": "Fc glycosylation affects ADCC efficacy", "mechanism": "Binds HER2 extracellular domain, inhibits signaling and induces ADCC", "protein": "Trastuzumab (anti-HER2 antibody)", "relationship_type": "therapeutic_agent", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation affects receptor localization and function", "mechanism": "ER positivity predicts response to hormone therapy", "protein": "Estrogen Receptor (ER)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Glycosylation may modulate receptor activity", "mechanism": "PR status guides hormone therapy decisions", "protein": "Progesterone Receptor (PR)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7120678" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "O-glycosylation patterns change in cancer, affecting immune recognition", "mechanism": "Overexpressed and aberrantly glycosylated in breast cancer; detected as CA15-3", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120678" }, { "confidence": "high", "disease": "Breast Cancer", "glycan_involvement": "Epitope is glycosylation-dependent", "mechanism": "Serum marker for monitoring disease recurrence", "protein": "CA15-3 (MUC1 epitope)", "relationship_type": "biomarker", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Ductal Carcinoma In Situ (DCIS)", "glycan_involvement": "N-glycosylation required for cell adhesion", "mechanism": "Loss of E-cadherin function promotes invasion", "protein": "E-cadherin (CDH1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "Highly glycosylated; glycan structure affects detection", "mechanism": "Elevated in some breast cancers; used for monitoring", "protein": "Carcinoembryonic Antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Breast Cancer", "glycan_involvement": "N-glycosylation modulates cell surface expression", "mechanism": "Overexpressed in breast cancer; involved in cell adhesion and proliferation", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7120678" }, { "confidence": "medium", "disease": "Triple Negative Breast Cancer", "glycan_involvement": "N-glycosylation required for transporter function", "mechanism": "Contributes to multidrug resistance", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120678" }, { "confidence": "high", "disease": "Familial Mediterranean Fever (FMF)", "glycan_involvement": "PGY1 is a glycosylated transporter; glycosylation affects its membrane localization and function.", "mechanism": "PGY1 regulates colchicine absorption and efflux, affecting drug response in FMF.", "protein": "P-glycoprotein 1 (PGY1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "high", "disease": "Gout", "glycan_involvement": "E-selectin glycosylation is essential for ligand binding and cell adhesion.", "mechanism": "Colchicine abrogates E-selectin-mediated neutrophil adhesion, reducing inflammation in gout.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "high", "disease": "Amyloidosis", "glycan_involvement": "SAA is glycosylated, influencing its aggregation and deposition.", "mechanism": "SAA deposition forms amyloid fibrils; colchicine reduces SAA-driven amyloidosis in FMF.", "protein": "Serum Amyloid A (SAA)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02735" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120738" }, { "confidence": "medium", "disease": "Scleroderma", "glycan_involvement": "TNFR glycosylation modulates receptor stability and signaling.", "mechanism": "Colchicine reduces TNF-\u03b1 receptor expression on endothelial cells, decreasing inflammation.", "protein": "Tumor Necrosis Factor Receptor (TNFR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "medium", "disease": "Beh\u00e7et Disease", "glycan_involvement": "ICAM-1 glycosylation is critical for leukocyte binding.", "mechanism": "Colchicine decreases ICAM-1 expression, inhibiting neutrophil migration in Beh\u00e7et disease.", "protein": "Intercellular Adhesion Molecule-1 (ICAM-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "medium", "disease": "Primary Biliary Cirrhosis (PBC)", "glycan_involvement": "Receptor glycosylation required for B12 binding and uptake.", "mechanism": "Colchicine reduces B12 absorption by decreasing glycoprotein receptor density in the intestine.", "protein": "Intrinsic Factor Receptor", "relationship_type": "causal", "source_pmcid": "PMC7120738" }, { "confidence": "high", "disease": "Familial Mediterranean Fever (FMF)", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Mutated pyrin forms inflammasome; colchicine modulates pyrin phosphorylation, reducing IL-1\u03b2 production.", "protein": "Pyrin", "protein_enriched": { "function": "Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:10807793, PubMed:11468188, PubMed:16037825, PubMed:16785446, PubMed:17431422, PubMed:1", "gene_name": "MEFV", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15553" }, "relationship_type": "causal", "source_pmcid": "PMC7120738" }, { "confidence": "medium", "disease": "Gout", "glycan_involvement": "No direct glycosylation involvement described.", "mechanism": "Colchicine suppresses caspase-1 activation, blocking IL-1\u03b2 maturation in gout.", "protein": "Caspase-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "medium", "disease": "Scleroderma", "glycan_involvement": "TGF-\u03b21 glycosylation affects secretion and receptor binding.", "mechanism": "Colchicine inhibits anti-TGF-\u03b21 activity, reducing fibrosis in scleroderma.", "protein": "Transforming Growth Factor Beta 1 (TGF-\u03b21)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120738" }, { "confidence": "low", "disease": "Amyloidosis", "glycan_involvement": "Albumin glycosylation influences its binding properties.", "mechanism": "Colchicine binds to albumin in plasma, affecting drug distribution and amyloid formation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120738" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation of G protein is critical for host cell binding and immune evasion.", "mechanism": "Mediates viral attachment to respiratory epithelial cells, initiating infection.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC7120754" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation affects fusion activity and antigenicity.", "mechanism": "Mediates fusion of viral and host membranes, syncytia formation, and cell entry.", "protein": "RSV F protein", "relationship_type": "causal", "source_pmcid": "PMC7120754" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Envelope glycoprotein; glycosylation may modulate function.", "mechanism": "Contributes to syncytia formation and inhibits apoptosis of infected cells.", "protein": "RSV SH protein", "relationship_type": "causal", "source_pmcid": "PMC7120754" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Glycosylation sites contribute to antigenic diversity and immune escape.", "mechanism": "Targeted by neutralizing antibodies; antigenic variation in G protein affects immunity.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120754" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Glycosylation influences antibody binding and neutralization.", "mechanism": "Target of monoclonal antibodies (palivizumab, motavizumab) for immunoprophylaxis.", "protein": "RSV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120754" }, { "confidence": "medium", "disease": "RSV infection", "glycan_involvement": "IgG1 is a glycoprotein; glycosylation affects effector function.", "mechanism": "Neutralizing antibodies against F and G glycoproteins confer partial protection.", "protein": "IgG1", "relationship_type": "protective", "source_pmcid": "PMC7120754" }, { "confidence": "medium", "disease": "RSV infection", "glycan_involvement": "IgA glycosylation is important for mucosal transport and function.", "mechanism": "Secretory IgA provides mucosal immunity in upper respiratory tract.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC7120754" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "SP-D is a glycoprotein; glycosylation affects pathogen binding.", "mechanism": "Polymorphisms associated with increased risk of severe RSV disease.", "protein": "Surfactant protein D", "relationship_type": "biomarker", "source_pmcid": "PMC7120754" }, { "confidence": "high", "disease": "RSV infection", "glycan_involvement": "Targets glycosylated F protein; antibody itself is glycosylated.", "mechanism": "Monoclonal antibody against F glycoprotein reduces RSV hospitalization in high-risk infants.", "protein": "Palivizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120754" }, { "confidence": "medium", "disease": "RSV infection", "glycan_involvement": "Targets glycosylated F protein; antibody is glycosylated.", "mechanism": "Second-generation monoclonal antibody with enhanced neutralizing activity against F glycoprotein.", "protein": "Motavizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120754" }, { "confidence": "high", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation critical for receptor binding and immune evasion.", "mechanism": "Mediates viral entry via sialic acid receptor binding; contains neutralizing epitopes.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "high", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Determines serotype specificity and is target for neutralizing antibodies and vaccines.", "protein": "S1 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7120852" }, { "confidence": "medium", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation may influence membrane fusion and infectivity.", "mechanism": "Anchors spike protein and aids in viral attachment to host cells.", "protein": "S2 subunit of Spike glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "medium", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Essential for virion assembly; interacts with S glycoprotein.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "high", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Recognizes mannose glycans on viral glycoproteins.", "mechanism": "Binds S1 glycoprotein, blocks viral attachment, and shapes innate/adaptive immunity.", "protein": "Chicken Mannose-Binding Lectin (MBL)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC7120852" }, { "confidence": "high", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation required for mucosal transport and stability.", "mechanism": "Secretory IgA in mucosa neutralizes virus and prevents infection.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC7120852" }, { "confidence": "high", "disease": "Avian Infectious Bronchitis (IB)", "glycan_involvement": "Glycosylation modulates effector functions.", "mechanism": "Serum IgG correlates with recovery and clearance of infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC7120852" }, { "confidence": "medium", "disease": "Nephritis", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Certain IBV variants with altered S1 glycoprotein tropism infect kidney cells causing nephritis.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "medium", "disease": "Oviduct damage/Abnormal egg production", "glycan_involvement": "Glycosylation may affect tissue targeting.", "mechanism": "IBV infects oviduct via S glycoprotein, leading to permanent damage and abnormal eggs.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "medium", "disease": "Enteritis", "glycan_involvement": "Glycosylation may modulate enteric tropism.", "mechanism": "IBV variants infect enteric surfaces via S glycoprotein, causing enteritis.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120852" }, { "confidence": "high", "disease": "Bronchiolitis Obliterans Syndrome (BOS)", "glycan_involvement": "F glycoprotein is highly glycosylated, mediating viral entry and immune recognition.", "mechanism": "RSV infection triggers immunologically mediated lung injury leading to BOS in transplant recipients.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "high", "disease": "Lower Respiratory Tract Infection (LRTI)", "glycan_involvement": "Glycosylation critical for fusion activity and immune evasion.", "mechanism": "RSV F glycoprotein mediates fusion and entry into respiratory epithelial cells, causing LRTI.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "high", "disease": "RSV infection (LRTI, BOS)", "glycan_involvement": "Targets glycosylated F protein; glycan shield may affect antibody binding.", "mechanism": "PVZ binds RSV F glycoprotein, neutralizing virus and preventing severe disease.", "protein": "Palivizumab (PVZ)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120918" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "N-glycosylation modulates receptor binding and antigenicity.", "mechanism": "HA mediates viral attachment and entry, leading to pneumonia in transplant recipients.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "high", "disease": "Viral Shedding/Prolonged Infection", "glycan_involvement": "Glycosylation affects enzymatic activity and immune recognition.", "mechanism": "NA cleaves sialic acids, facilitating viral release and prolonged shedding in immunocompromised hosts.", "protein": "Influenza Neuraminidase (NA)", "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "medium", "disease": "Acute Allograft Rejection", "glycan_involvement": "Glycosylation required for receptor binding and immune modulation.", "mechanism": "PIV HN glycoprotein mediates infection, triggering immune responses leading to rejection.", "protein": "Parainfluenza Virus Hemagglutinin-Neuraminidase (HN)", "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "medium", "disease": "Acute Allograft Rejection", "glycan_involvement": "Glycosylation modulates fusion and immune evasion.", "mechanism": "HMPV F glycoprotein mediates viral entry, associated with acute rejection in lung transplants.", "protein": "Human Metapneumovirus Fusion Glycoprotein (F)", "protein_enriched": { "function": "", "gene_name": "Knop1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Z2Q2" }, "relationship_type": "causal", "source_pmcid": "PMC7120918" }, { "confidence": "medium", "disease": "Parainfluenza Virus LRTI", "glycan_involvement": "Targets host cell surface glycans (sialic acids).", "mechanism": "DAS181 removes sialic acids, preventing viral entry and treating PIV LRTI.", "protein": "DAS181 (sialidase fusion protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120918" }, { "confidence": "medium", "disease": "HMPV LRTI", "glycan_involvement": "Glycosylation of F protein may affect antibody efficacy.", "mechanism": "Antibodies neutralize HMPV by binding F glycoprotein, preventing infection.", "protein": "Monoclonal antibodies against HMPV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120918" }, { "confidence": "medium", "disease": "RSV LRTI", "glycan_involvement": "Targets viral glycoproteins; glycan structures may influence neutralization.", "mechanism": "RSV-IVIG provides passive immunity against RSV glycoproteins, reducing severity.", "protein": "RSV-IVIG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7120918" }, { "confidence": "high", "disease": "Pseudomonas aeruginosa infection", "glycan_involvement": "Shedding of HS chains from syndecan-1 ectodomain modulates host-pathogen interaction.", "mechanism": "P. aeruginosa LasA induces syndecan-1 shedding, enhancing bacterial virulence and tissue damage.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "HS chains on syndecan-1 are shed, altering host defense.", "mechanism": "S. aureus induces syndecan-1 shedding, promoting bacterial dissemination and inflammation.", "protein": "Syndecan-1", "protein_enriched": { "function": "Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert", "gene_name": "SDC1", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G73004SD", "G58001LT", "G29068FM", "G43417UB", "G49108TO", "G53434XO", "G57317CE" ], "uniprot_id": "P18827" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "HS glycosaminoglycan chains mediate viral binding and internalization.", "mechanism": "Dengue E protein binds cell surface HSPGs for initial attachment and entry.", "protein": "Envelope (E) protein (Dengue virus)", "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Listeriosis", "glycan_involvement": "HS chains on host cells facilitate bacterial adherence and entry.", "mechanism": "Listeria ActA binds HSPGs to mediate attachment and invasion of epithelial cells.", "protein": "ActA", "protein_enriched": { "function": "Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8Y6X6" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "HS chain sulfation and size determine Tat binding and uptake.", "mechanism": "Tat binds HSPGs for internalization and transactivation of host genes; also mediates lymphoid cell extravasation.", "protein": "Tat (HIV-1)", "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "HS chains interact with gp120 heparin-binding domains, enhancing viral entry.", "mechanism": "gp120 binds HSPGs to concentrate virus on cell surface, facilitating infection.", "protein": "gp120 (HIV-1)", "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "O- and N-sulfation of HS chains critical for viral binding and infectivity.", "mechanism": "HPV L1 binds HSPGs for initial attachment; required for infection by oncogenic HPV strains.", "protein": "L1 (HPV)", "protein_enriched": { "function": "Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan s", "gene_name": "L1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03101" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Malaria", "glycan_involvement": "Degree of HS sulfation regulates tissue tropism and invasion.", "mechanism": "CSP binds highly sulfated HSPGs on hepatocytes, triggering cleavage and productive invasion.", "protein": "Circumsporozoite protein (CSP)", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8I4C6" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Pregnancy-associated malaria", "glycan_involvement": "Specific CS glycosylation enables placental binding.", "mechanism": "VAR2CSA binds placental chondroitin sulfate proteoglycan, mediating sequestration of infected erythrocytes.", "protein": "VAR2CSA", "protein_enriched": { "function": "", "gene_name": "unc-61", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8I4C9" }, "relationship_type": "causal", "source_pmcid": "PMC7120983" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Cleavage of core protein releases HS-modified fragment.", "mechanism": "Shedding of glypican-3 ectodomain detected in serum of patients.", "protein": "Glypican-3", "protein_enriched": { "function": "Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for b", "gene_name": "GPC3", "glycan_count": 12, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02815KT", "G31852PQ", "G41071NU", "G45395BF", "G62765YT", "G80920RR", "G27058EU", "G37412TK", "G81315DD", "G57321FI", "G49108TO" ], "uniprot_id": "P51654" }, "relationship_type": "biomarker", "source_pmcid": "PMC7120983" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "GPVI is a glycoprotein; glycosylation may affect receptor-virus interaction.", "mechanism": "GPVI mediates HCV binding to platelets, leading to altered function and reduced platelet count.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "Dengue Fever", "glycan_involvement": "DC-SIGN recognizes high-mannose glycans on viral envelope glycoproteins.", "mechanism": "DC-SIGN on platelets binds DENV, facilitating viral entry and replication, contributing to thrombocytopenia and hemorrhagic manifestations.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "gB is heavily glycosylated; glycan structures are essential for TLR2 recognition.", "mechanism": "CMV gB interacts with platelet TLR2, activating platelets and promoting clearance.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "P-selectin binds sialylated glycoproteins on leukocytes.", "mechanism": "CMV-induced platelet activation via TLR2 increases P-selectin expression, promoting leukocyte recruitment to atherosclerotic plaques.", "protein": "P-selectin (CD62P)", "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "Acute Lung Injury", "glycan_involvement": "HA binds sialic acid glycans on platelet surface; neuraminidase activity removes sialic acid, promoting clearance.", "mechanism": "IAV HA binds platelets, induces activation via PARs, leading to neutrophil recruitment and lung injury.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "HIV-associated neuroinflammation", "glycan_involvement": "gp120 is highly glycosylated; glycans mediate immune evasion and receptor binding.", "mechanism": "Platelet-released CXCL4 binds HIV-1 gp120, inhibiting infection; platelet-monocyte complexes promote neuroinflammation.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "CAR is a glycoprotein; glycosylation may modulate virus-receptor interaction.", "mechanism": "CAR mediates adenovirus binding and entry into platelets, leading to activation and clearance.", "protein": "CAR (Coxsackie-adenovirus receptor)", "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "Hantavirus-induced renal syndrome", "glycan_involvement": "Integrins are glycoproteins; glycosylation affects ligand binding.", "mechanism": "Hantavirus binds platelet integrin \u03b1IIb\u03b23, causing activation, clearance, and increased vascular permeability.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "CR2 is glycosylated; glycans may influence EBV binding.", "mechanism": "CR2 on platelets binds EBV, potentially protecting virus from complement and promoting platelet clearance.", "protein": "CR2 (Complement receptor 2)", "protein_enriched": { "function": "Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1 (PubMed:1849076, PubMed:21527715, PubMed:7753047). When C3d is bound to antigens, attaches to C3d on B-cel", "gene_name": "CR2", "glycan_count": 5, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G80920RR", "G41071NU", "G87661QW", "G62765YT", "G93910IH" ], "uniprot_id": "P20023" }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "medium", "disease": "Cytomegalovirus-induced vascular disease", "glycan_involvement": "gH glycosylation is important for TLR2 interaction.", "mechanism": "CMV gH interacts with platelet TLR2, leading to VEGF release and vascular pathology.", "protein": "Glycoprotein H (gH)", "protein_enriched": { "function": "Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional re", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09265" }, "relationship_type": "causal", "source_pmcid": "PMC7121037" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is heavily glycosylated; glycans mediate nanoparticle binding and shield viral epitopes.", "mechanism": "Silver nanoparticles bind to gp120 glycoprotein knobs, inhibiting HIV-1 attachment to host cells.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "F protein is glycosylated, affecting antibody recognition and detection sensitivity.", "mechanism": "F protein remains on infected cell surface and is targeted by antibody-conjugated quantum dots for early RSV detection.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "G protein glycosylation influences antigenicity and detection.", "mechanism": "G protein on cell surface is detected by quantum dot-labeled antibodies for rapid RSV diagnosis.", "protein": "G protein", "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "Knob protein glycosylation affects receptor binding and biosensor specificity.", "mechanism": "Knob protein immobilized on carbon nanotubes retains activity for biosensor detection of adenovirus.", "protein": "Knob protein (Ad12)", "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "CAR glycosylation modulates virus-receptor interaction.", "mechanism": "CAR protein on nanotubes binds Knob protein, enabling biosensor detection of adenovirus.", "protein": "CAR protein", "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "E. coli infection", "glycan_involvement": "O-antigen is a glycan; its absence exposes bacterial surface for probe binding.", "mechanism": "QDs stain rough E. coli mutants lacking O-antigen, enabling optical detection in infection models.", "protein": "O-antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "Staphylococcus aureus infection", "glycan_involvement": "Spa glycosylation may affect antibody binding and targeting efficiency.", "mechanism": "Antibody-conjugated gold nanocages target Spa for selective delivery of antibiotics and photothermal therapy.", "protein": "Staphylococcal protein A (Spa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121058" }, { "confidence": "medium", "disease": "Kidney stone disease", "glycan_involvement": "Albumin glycosylation may influence mineralization and aggregation.", "mechanism": "Nanobacteria-like particles react with anti-nanobacteria antibodies that cross-react with serum albumin, suggesting protein involvement in stone formation.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "Anthrax", "glycan_involvement": "Spore surface carbohydrates are glycan targets for therapeutic binding.", "mechanism": "Multivalent monosaccharide ligands on SWCNTs bind anthrax spore surface carbohydrates, causing aggregation and inhibiting infection.", "protein": "Anthrax spore surface carbohydrate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121058" }, { "confidence": "medium", "disease": "Arteriosclerosis/calcific arterial disease", "glycan_involvement": "Glycoprotein calcification contributes to disease pathology.", "mechanism": "Nanobacteria-associated calcified proteins and glycoproteins found in arterial plaques suggest a role in vascular calcification.", "protein": "Bacterial cell wall glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7121058" }, { "confidence": "high", "disease": "Allergic Contact Dermatitis", "glycan_involvement": "CD86 is a glycoprotein; glycosylation affects cell surface expression and immune signaling.", "mechanism": "Elevated CD86 expression drives inflammation; siRNA silencing reduces immune response.", "protein": "CD86", "protein_enriched": { "function": "Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4 (PubMed:12196291). May play a critical role in the early ", "gene_name": "CD86", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P42081" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "Psoriasis", "glycan_involvement": "TNF-\u03b1 glycosylation modulates secretion and receptor binding.", "mechanism": "Overproduction of TNF-\u03b1 leads to inflammation and keratinocyte proliferation; siRNA silencing improves lesions.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "APP is heavily glycosylated; glycosylation affects processing and aggregation.", "mechanism": "APP cleavage produces amyloid \u03b2-peptide; siRNA targeting APP reduces A\u03b2 formation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "Alzheimer's Disease", "glycan_involvement": "BACE1 glycosylation regulates enzyme activity and trafficking.", "mechanism": "BACE1 cleaves APP to generate A\u03b2; siRNA silencing reduces amyloid pathology.", "protein": "BACE1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "CFTR glycosylation is essential for proper folding and membrane localization.", "mechanism": "Mutated CFTR impairs chloride transport; siRNA modulates downstream inflammation.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC7121101" }, { "confidence": "medium", "disease": "Cystic Fibrosis", "glycan_involvement": "ENaC glycosylation affects channel function and stability.", "mechanism": "ENaC overactivity exacerbates mucus dehydration; siRNA silencing normalizes ion transport.", "protein": "ENaC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "CCR5 glycosylation modulates receptor conformation and virus binding.", "mechanism": "CCR5 acts as HIV co-receptor; siRNA silencing blocks viral entry.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "medium", "disease": "HIV Infection", "glycan_involvement": "CD4 glycosylation influences HIV binding and immune signaling.", "mechanism": "CD4 is primary HIV receptor; siRNA targeting reduces infection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "medium", "disease": "Intracranial Tumors", "glycan_involvement": "EGFR glycosylation affects ligand binding and receptor activation.", "mechanism": "EGFR overexpression drives tumor growth; siRNA silencing inhibits proliferation.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "medium", "disease": "Gastric Tumor", "glycan_involvement": "NF-kB p65 is not classically glycosylated, but upstream glycoprotein signaling may regulate its activity.", "mechanism": "NF-kB p65 promotes tumor survival and chemoresistance; siRNA silencing induces apoptosis.", "protein": "NF-kB p65", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121101" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily N-glycosylated; glycans shield Env from immune recognition.", "mechanism": "Mediates viral entry into host cells; extensive alternative splicing produces multiple Env isoforms.", "protein": "HIV-1 Env", "relationship_type": "causal", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycans modulate immune evasion and receptor binding.", "mechanism": "gp120 is a major surface glycoprotein detected in diagnostics; spliced mRNA indicates active replication.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects receptor binding and antigenicity.", "mechanism": "HA mediates viral attachment and entry; spliced transcripts indicate active infection.", "protein": "Influenza A Hemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycans influence drug sensitivity and immune recognition.", "mechanism": "NA is targeted by antivirals; glycosylation modulates enzyme activity.", "protein": "Influenza A Neuraminidase (NA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121103" }, { "confidence": "medium", "disease": "HTLV-associated leukemia", "glycan_involvement": "N-glycosylation required for proper folding and infectivity.", "mechanism": "Env glycoprotein mediates cell entry; spliced mRNA indicates active viral gene expression.", "protein": "HTLV-1 Env", "relationship_type": "causal", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation affects secretion and immunogenicity.", "mechanism": "HBsAg is detected in blood as a marker of infection; spliced transcripts indicate active replication.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC7121103" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "O-glycosylation modulates tropism and immune evasion.", "mechanism": "Fiber protein mediates host cell attachment; splicing regulates isoform diversity.", "protein": "Adenovirus Fiber protein", "relationship_type": "causal", "source_pmcid": "PMC7121103" }, { "confidence": "medium", "disease": "Herpesvirus infection", "glycan_involvement": "N-glycans modulate fusion activity and immune evasion.", "mechanism": "gB is a major envelope glycoprotein; spliced mRNA distinguishes lytic from latent infection.", "protein": "Herpesvirus gB", "relationship_type": "biomarker", "source_pmcid": "PMC7121103" }, { "confidence": "medium", "disease": "Papillomavirus infection", "glycan_involvement": "N-glycosylation affects capsid assembly and immunogenicity.", "mechanism": "L1 is the major capsid protein; spliced mRNA indicates productive infection.", "protein": "Papillomavirus L1", "relationship_type": "biomarker", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycans modulate fusion and antibody accessibility.", "mechanism": "gp41 mediates membrane fusion; targeted by entry inhibitors.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121103" }, { "confidence": "high", "disease": "Anemia of critical illness", "glycan_involvement": "N-glycosylation critical for EPO stability and activity.", "mechanism": "EPO stimulates erythropoiesis; decreased EPO or blunted response contributes to anemia.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121187" }, { "confidence": "high", "disease": "Hemolytic anemia", "glycan_involvement": "N-glycosylation affects haptoglobin clearance and function.", "mechanism": "Low haptoglobin indicates hemolysis due to binding of free hemoglobin.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121187" }, { "confidence": "medium", "disease": "Anemia of critical illness", "glycan_involvement": "N-glycosylation modulates transferrin receptor binding.", "mechanism": "Transferrin saturation reflects iron availability for erythropoiesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121187" }, { "confidence": "medium", "disease": "Anemia of critical illness", "glycan_involvement": "Glycosylation influences ferritin secretion and stability.", "mechanism": "Serum ferritin reflects iron stores; acute phase reactant in inflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121187" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation required for secretion and bioactivity.", "mechanism": "Regulates platelet production; decreased in liver disease.", "protein": "Thrombopoietin", "protein_enriched": { "function": "Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:11741539, PubMed:9230079). The Arp2/3 complex m", "gene_name": "ARPC1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15143" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121187" }, { "confidence": "high", "disease": "Drug-induced thrombocytopenia", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Target of drug-dependent antibodies causing platelet destruction.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "causal", "source_pmcid": "PMC7121187" }, { "confidence": "high", "disease": "Immune Thrombocytopenic Purpura (ITP)", "glycan_involvement": "Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG blocks Fc receptors, reducing platelet destruction.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121187" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "N- and O-glycosylation regulate vWF multimerization and function.", "mechanism": "vWF levels altered in DIC, affecting platelet adhesion.", "protein": "Von Willebrand Factor", "relationship_type": "biomarker", "source_pmcid": "PMC7121187" }, { "confidence": "high", "disease": "Neutropenia", "glycan_involvement": "N-glycosylation required for G-CSF stability and activity.", "mechanism": "G-CSF stimulates neutrophil production in neutropenic states.", "protein": "Granulocyte Colony Stimulating Factor (G-CSF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121187" }, { "confidence": "medium", "disease": "Transfusion-related acute lung injury (TRALI)", "glycan_involvement": "HLA glycosylation affects antigenicity and antibody recognition.", "mechanism": "HLA antibodies in donor plasma trigger immune-mediated lung injury.", "protein": "Human Leukocyte Antigen (HLA)", "relationship_type": "causal", "source_pmcid": "PMC7121187" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavy N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates viral entry by binding CD4 and co-receptors on host cells.", "protein": "HIV Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7121188" }, { "confidence": "high", "disease": "Herpes Simplex Virus Infection", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "gD binds to host cell receptors to facilitate viral entry.", "protein": "Herpes Simplex Virus Glycoprotein D (gD)", "relationship_type": "causal", "source_pmcid": "PMC7121188" }, { "confidence": "medium", "disease": "Human Papillomavirus Infection/Cervical Cancer", "glycan_involvement": "Glycosylation affects immunogenicity and vaccine efficacy.", "mechanism": "L1 forms the viral capsid and is the target of vaccine-induced immunity.", "protein": "Human Papillomavirus L1 Major Capsid Protein", "relationship_type": "biomarker", "source_pmcid": "PMC7121188" }, { "confidence": "high", "disease": "Avian Influenza", "glycan_involvement": "Glycosylation modulates receptor specificity and antigenicity.", "mechanism": "HA binds sialic acid on host cells to mediate viral entry.", "protein": "Influenza Virus Hemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7121188" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation shields epitopes and affects infectivity.", "mechanism": "Spike protein binds ACE2 receptor for viral entry.", "protein": "SARS Coronavirus Spike Glycoprotein (S)", "relationship_type": "causal", "source_pmcid": "PMC7121188" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Acts as a biomarker for natural exposure or immunization; detected by LIPS assay.", "protein": "RSV G-Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Influenza (H1N1, H9N2)", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Surface glycoprotein mediates viral entry via sialic acid binding; detected by biosensor and ELISA.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Dengue Fever", "glycan_involvement": "Glycosylation influences antigenicity and cross-reactivity.", "mechanism": "Envelope glycoprotein used for serological and SPR-based diagnosis.", "protein": "Dengue Virus Envelope Protein (E)", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Zika Virus Infection", "glycan_involvement": "Glycosylation affects immune response and diagnostic specificity.", "mechanism": "Envelope glycoprotein detected by multiplex immunoassays and biosensors.", "protein": "Zika Virus Envelope Protein (E)", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation critical for antigenicity and secretion.", "mechanism": "Surface glycoprotein detected by ECL immunosensor for diagnosis.", "protein": "Hepatitis B Virus Surface Antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "medium", "disease": "Hendra/Nipah Virus Infection", "glycan_involvement": "Glycosylation modulates host cell attachment and immune recognition.", "mechanism": "G glycoprotein used in ELISA for detection of specific antibodies.", "protein": "Hendra/Nipah Virus G Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "medium", "disease": "Crimean\u2013Congo Hemorrhagic Fever", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Recombinant nucleoprotein used in ELISA for IgM/IgG detection.", "protein": "Crimean\u2013Congo Hemorrhagic Fever Virus Nucleoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation influences antigen stability and detection.", "mechanism": "Core antigen quantification used for diagnosis of chronic infection.", "protein": "Hepatitis C Virus Core Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation modulates neuroinvasiveness and immune response.", "mechanism": "Glycoprotein detected by immunofluorescence and PCR-based assays.", "protein": "Rabies Virus Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Spike glycoprotein detected by RT-LAMP and PCR assays.", "protein": "Middle East Respiratory Syndrome Coronavirus Spike Protein", "relationship_type": "biomarker", "source_pmcid": "PMC7121190" }, { "confidence": "high", "disease": "Spanish influenza", "glycan_involvement": "Glycosylation of HA affects receptor binding and antigenicity.", "mechanism": "HA mediates viral entry by binding to sialic acid residues on host cells.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H1N1 flu virus (Swine flu)", "glycan_involvement": "Glycosylation modulates immune recognition and vaccine efficacy.", "mechanism": "HA is a major antigenic determinant and target for peptide vaccines.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H5N1 avian flu (Bird flu)", "glycan_involvement": "Glycosylation sites influence host adaptation and immune escape.", "mechanism": "HA is essential for host specificity and viral infectivity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "Spanish influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and antigenic properties.", "mechanism": "NA cleaves sialic acid to facilitate viral release from host cells.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H1N1 flu virus (Swine flu)", "glycan_involvement": "Glycosylation modulates drug sensitivity and immune response.", "mechanism": "NA is targeted by antiviral drugs and peptide vaccines.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H5N1 avian flu (Bird flu)", "glycan_involvement": "Glycosylation sites contribute to antigenic drift and shift.", "mechanism": "NA is critical for viral spread and pathogenesis.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121243" }, { "confidence": "medium", "disease": "H1N1 flu virus (Swine flu)", "glycan_involvement": "Glycosylation patterns help track viral evolution.", "mechanism": "Conserved HA segments serve as molecular markers for surveillance.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7121243" }, { "confidence": "medium", "disease": "H5N1 avian flu (Bird flu)", "glycan_involvement": "Glycosylation changes indicate antigenic drift.", "mechanism": "Conserved NA regions are used for molecular surveillance.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H5N1 avian flu (Bird flu)", "glycan_involvement": "Altered glycosylation enables immune evasion.", "mechanism": "Mutations and recombination in HA drive antigenic shift and pandemic potential.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "H1N1 flu virus (Swine flu)", "glycan_involvement": "Glycosylation changes affect drug resistance.", "mechanism": "NA mutations contribute to antigenic drift and resistance.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "causal", "source_pmcid": "PMC7121243" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Anti-MOG antibodies are present in serum/CSF during acute ADEM and decline with recovery; may indicate MOG-driven autoimmunity.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121338" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG may influence immune recognition.", "mechanism": "Anti-MOG antibodies are rare in MS, helping distinguish ADEM from MS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC7121338" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Presence of anti-AQP4 antibodies rules out ADEM and suggests NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "differential biomarker", "source_pmcid": "PMC7121338" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "MBP is not glycosylated; no direct glycan involvement.", "mechanism": "Autoantibodies against MBP found in ADEM; molecular mimicry with pathogens may trigger T-cell response.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "autoantigen", "source_pmcid": "PMC7121338" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "PLP is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against PLP found in ADEM; may contribute to demyelination.", "protein": "Proteolipid protein (PLP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "autoantigen", "source_pmcid": "PMC7121338" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "MOBP is a glycoprotein; glycosylation may influence immune response.", "mechanism": "Autoantibodies against MOBP described in ADEM; may participate in immune-mediated demyelination.", "protein": "Myelin-associated oligodendrocyte basic protein (MOBP)", "relationship_type": "autoantigen", "source_pmcid": "PMC7121338" }, { "confidence": "low", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "OSP is a glycoprotein; glycosylation may modulate antigenicity.", "mechanism": "OSP shares antigenic determinants with pathogens; may be targeted by immune response in ADEM.", "protein": "Oligodendrocyte-specific protein (OSP/Claudin-11)", "protein_enriched": { "function": "Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity", "gene_name": "CLDN11", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O75508" }, "relationship_type": "autoantigen", "source_pmcid": "PMC7121338" }, { "confidence": "low", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Alpha-B crystallin is a glycoprotein; glycosylation may affect immune recognition.", "mechanism": "IgG autoantibodies to alpha-B crystallin found in ADEM; may help distinguish from MS.", "protein": "Alpha-B crystallin", "relationship_type": "autoantigen", "source_pmcid": "PMC7121338" }, { "confidence": "medium", "disease": "Acute hemorrhagic leukoencephalitis (AHLE)", "glycan_involvement": "Glycosylation of MOG may influence antibody binding.", "mechanism": "Anti-MOG antibodies may be present in severe ADEM variants like AHLE.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121338" }, { "confidence": "medium", "disease": "Acute transverse myelitis (ATM)", "glycan_involvement": "MOG glycosylation may affect immune response.", "mechanism": "Anti-MOG antibodies may be detected in ATM cases associated with ADEM.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121338" }, { "confidence": "high", "disease": "Gaucher\u2019s disease", "glycan_involvement": "Plant-specific N-glycans enable macrophage targeting", "mechanism": "Enzyme replacement therapy for \u03b2-glucocerebrosidase deficiency", "protein": "Taliglucerase alfa", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity", "mechanism": "Induces protective immune response against HBV", "protein": "Hepatitis B virus surface antigen (HBsAg)", "relationship_type": "protective (vaccine antigen)", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Influenza (H1N1, H5N1)", "glycan_involvement": "N-glycosylation modulates immunogenicity and folding", "mechanism": "Induces neutralizing antibodies to prevent infection", "protein": "Influenza hemagglutinin (HA)", "relationship_type": "protective (vaccine antigen)", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation shields epitopes, affects antibody binding", "mechanism": "Elicits immune response or is targeted by neutralizing antibodies", "protein": "Ebola virus glycoprotein (GP)", "relationship_type": "protective (vaccine antigen) / therapeutic (antibody target)", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense N-glycan shield is main target for 2G12", "mechanism": "Target for broadly neutralizing antibodies (e.g., 2G12)", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Breast cancer (HER2+)", "glycan_involvement": "Fc N-glycosylation modulates ADCC", "mechanism": "Binds HER2 receptor, inhibits tumor growth", "protein": "Trastuzumab", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Non-Hodgkin lymphoma", "glycan_involvement": "Fc glycosylation affects ADCC and CDC", "mechanism": "Targets CD20 on B cells, induces cell death", "protein": "Rituximab", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Non-Hodgkin lymphoma", "glycan_involvement": "Engineered Fc N-glycans enhance ADCC", "mechanism": "Targets CD20, induces enhanced cell death", "protein": "Obinutuzumab", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "medium", "disease": "Respiratory syncytial virus (RSV) infection", "glycan_involvement": "Fc glycosylation modulates effector function", "mechanism": "Neutralizes RSV by binding F protein", "protein": "Palivizumab", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Recognizes specific N-glycan clusters on gp120", "mechanism": "Neutralizes HIV by binding high-mannose glycans on gp120", "protein": "2G12", "relationship_type": "therapeutic", "source_pmcid": "PMC7121380" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation affects CRP stability and function.", "mechanism": "CRP levels rise in response to inflammation and infection.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121391" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation influences serum half-life and detection.", "mechanism": "PCT increases in bacterial infection; correlates with severity and guides antibiotic therapy.", "protein": "Procalcitonin (PCT)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates membrane localization.", "mechanism": "Secreted by endothelial cells in response to LPS; indicates endothelial activation.", "protein": "Moesin", "protein_enriched": { "function": "Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers a", "gene_name": "MSN", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P26038" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121391" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Elevated suPAR predicts severity and mortality in sepsis/SIRS.", "protein": "Soluble urokinase plasminogen activator receptor (suPAR)", "protein_enriched": { "function": "Inhibits gastrointestinal motility and gastric acid secretion. Could function as a structural component of gastric mucus, possibly by stabilizing glycoproteins in the mucus gel through interactions wi", "gene_name": "TFF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G92551JA" ], "uniprot_id": "Q03403" }, "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect mitochondrial targeting.", "mechanism": "Circulating CPS-1 reflects mitochondrial damage in liver during sepsis.", "protein": "Carbamoyl phosphate synthase-1 (CPS-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Meningococcal sepsis", "glycan_involvement": "O-glycosylation modulates receptor binding.", "mechanism": "Serum chemokine levels correlate with severity and mortality.", "protein": "Chemokines (CC/CXC)", "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "VCAM-1 levels inversely associated with CoQ10 in septic shock.", "protein": "Endothelial cell adhesion molecule (VCAM-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "O-glycosylation affects secretion.", "mechanism": "Serum CGA increases in SIRS, correlates with severity and poor outcome.", "protein": "Chromogranin A (CGA)", "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC7121391" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation essential for antigenicity and immune evasion.", "mechanism": "Presence of HBsAg indicates HBV infection and viral replication.", "protein": "HBV surface antigen (HBsAg)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121391" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "O-glycosylation modulates chemotactic activity.", "mechanism": "High plasma IP-10 predicts poor response to HCV therapy.", "protein": "IP-10 (CXCL10)", "relationship_type": "biomarker/prognostic", "source_pmcid": "PMC7121391" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation of gp120 is essential for receptor binding and immune evasion.", "mechanism": "gp120 binds to CD4 receptor on host T-cells, mediating viral entry and infection.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation affects gp41 conformation and fusion activity.", "mechanism": "gp41 mediates fusion of viral and host cell membranes after gp120-CD4 binding.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CD4 is a glycoprotein; glycosylation affects its structure and HIV binding.", "mechanism": "CD4 is the primary host receptor for HIV entry via gp120 binding.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CCR5 glycosylation modulates receptor function and HIV tropism.", "mechanism": "CCR5 acts as a co-receptor for HIV entry; homozygous CCR5 mutation confers resistance.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/protective", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation influences CXCR4-HIV interaction.", "mechanism": "CXCR4 serves as an alternative co-receptor for HIV entry, especially in late-stage infection.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Indirect; Nef affects trafficking of glycoprotein receptors.", "mechanism": "Nef downregulates CD4 and chemokine receptors, enhancing viral infectivity and pathogenesis.", "protein": "Nef", "protein_enriched": { "function": "Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host ", "gene_name": "nef", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03407" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "medium", "disease": "NeuroAIDS", "glycan_involvement": "No direct glycosylation, but may affect glycoprotein signaling.", "mechanism": "Tat induces neuronal apoptosis and CNS pathology via oxidative stress.", "protein": "Tat", "protein_enriched": { "function": "Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04612" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation shields epitopes from immune recognition.", "mechanism": "gp160 is cleaved to gp120/gp41, both essential for viral entry; targeted by fusion inhibitors.", "protein": "Env (gp160 precursor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121508" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Indirect; affects trafficking of glycoprotein CD4.", "mechanism": "Vpu enhances viral particle release and degrades CD4.", "protein": "Vpu", "protein_enriched": { "function": "Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor CD4 i", "gene_name": "vpu", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P05919" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "medium", "disease": "Astrocyte dysfunction", "glycan_involvement": "Indirect; Nef modulates glycoprotein receptor expression.", "mechanism": "High Nef levels alter astrocyte growth and neuronal electrophysiology.", "protein": "Nef", "protein_enriched": { "function": "Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host ", "gene_name": "nef", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03407" }, "relationship_type": "causal", "source_pmcid": "PMC7121508" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation affects stability and secretion of cathelicidin.", "mechanism": "Reduced expression due to VDR dysregulation leads to impaired innate immunity.", "protein": "Cathelicidin", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation modulates antimicrobial activity.", "mechanism": "Diminished expression from VDR dysregulation impairs mucosal defense.", "protein": "Beta-defensin", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation may affect VDR stability and nuclear localization.", "mechanism": "Pathogen-induced VDR downregulation reduces AMP expression, promoting inflammation.", "protein": "Vitamin D Receptor (VDR)", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Sarcoidosis", "glycan_involvement": "N-glycosylation critical for TLR2 function.", "mechanism": "VDR regulates TLR2; dysregulation impairs pathogen recognition.", "protein": "Toll-like receptor 2 (TLR2)", "protein_enriched": { "function": "Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bac", "gene_name": "TLR2", "glycan_count": 16, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G08146BT", "G22310AV", "G71146HJ", "G75983OB", "G00912UN", "G25451PN", "G27058EU", "G40926MX", "G45395BF", "G45495MK", "G62765YT", "G70101JE", "G80920RR", "G83229XP", "G84452RH", "G83460ZZ" ], "uniprot_id": "O60603" }, "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Potential glycosylation affects phosphatase activity.", "mechanism": "Upregulated by bacterial metagenome, modulating immune signaling.", "protein": "PTPN22", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Sarcoidosis", "glycan_involvement": "Glycosylation influences ACE activity and serum levels.", "mechanism": "ACE expression modulated by microbiota-derived peptides; used as a disease marker.", "protein": "ACE", "relationship_type": "biomarker", "source_pmcid": "PMC7121718" }, { "confidence": "low", "disease": "Hashimoto\u2019s Thyroiditis", "glycan_involvement": "Glycosylation may modulate receptor function.", "mechanism": "EBV infection downregulates ERB, affecting immune regulation.", "protein": "Estrogen Receptor Beta (ERB)", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Lupus", "glycan_involvement": "Glycosylation affects receptor signaling.", "mechanism": "Dysregulation by high 1,25-D impairs AMP expression and immune homeostasis.", "protein": "Glucocorticoid Receptor", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation impacts peptide function.", "mechanism": "Reduced AMP expression from VDR dysregulation may promote CNS infection/inflammation.", "protein": "Cathelicidin", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "medium", "disease": "Irritable Bowel Syndrome", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Altered microbiota reduces beta-defensin, impairing mucosal defense.", "protein": "Beta-defensin", "relationship_type": "causal", "source_pmcid": "PMC7121718" }, { "confidence": "high", "disease": "Lassa Fever", "glycan_involvement": "GPC is glycosylated, enabling proper folding, receptor binding, and immune evasion.", "mechanism": "GPC is essential for arenavirus infectivity and pathogenesis; its cleavage by SKI-1/S1P is required for production of infectious particles.", "protein": "Arenavirus Envelope Glycoprotein Precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Lassa Fever", "glycan_involvement": "SKI-1/S1P processes glycoprotein substrates, including viral GPC.", "mechanism": "SKI-1/S1P is hijacked by arenaviruses for GPC maturation; inhibition blocks viral infectivity.", "protein": "SKI-1/S1P (Site-1 Protease)", "protein_enriched": { "function": "Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20", "gene_name": "MBTPS1", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G31852PQ", "G46524LG", "G51653BI", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G57321FI", "G49108TO", "G15664MX" ], "uniprot_id": "Q14703" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Argentine Hemorrhagic Fever", "glycan_involvement": "Glycosylation of GPC is necessary for proper function and immune evasion.", "mechanism": "GPC cleavage by SKI-1/S1P is required for Junin virus infectivity.", "protein": "Arenavirus Envelope Glycoprotein Precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Hypercholesterolemia", "glycan_involvement": "SKI-1/S1P processes glycoprotein transcription factors.", "mechanism": "SKI-1/S1P activates SREBP, regulating cholesterol biosynthesis; dysregulation leads to hypercholesterolemia.", "protein": "SKI-1/S1P (Site-1 Protease)", "protein_enriched": { "function": "Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20", "gene_name": "MBTPS1", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G31852PQ", "G46524LG", "G51653BI", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G57321FI", "G49108TO", "G15664MX" ], "uniprot_id": "Q14703" }, "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "medium", "disease": "Vascular Diseases", "glycan_involvement": "Processes glycoprotein substrates involved in vascular function.", "mechanism": "SKI-1/S1P regulates lipid metabolism and vascular homeostasis via SREBP activation.", "protein": "SKI-1/S1P (Site-1 Protease)", "protein_enriched": { "function": "Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20", "gene_name": "MBTPS1", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G31852PQ", "G46524LG", "G51653BI", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G57321FI", "G49108TO", "G15664MX" ], "uniprot_id": "Q14703" }, "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Processes glycoprotein transcription factors.", "mechanism": "SKI-1/S1P implicated in cancer via regulation of transcription factors and cell signaling.", "protein": "SKI-1/S1P (Site-1 Protease)", "protein_enriched": { "function": "Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20", "gene_name": "MBTPS1", "glycan_count": 10, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G31852PQ", "G46524LG", "G51653BI", "G62765YT", "G80920RR", "G83460ZZ", "G83633GK", "G57321FI", "G49108TO", "G15664MX" ], "uniprot_id": "Q14703" }, "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Lysosomal Storage Disorders", "glycan_involvement": "GNPTAB is a glycoprotein involved in glycan-dependent lysosomal targeting.", "mechanism": "SKI-1/S1P processes GNPTAB, required for lysosomal protein sorting; defects cause lysosomal storage diseases.", "protein": "GNPTAB", "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "medium", "disease": "ER Stress-related Disorders", "glycan_involvement": "ATF6 is a glycoprotein transcription factor.", "mechanism": "SKI-1/S1P processes ATF6, regulating ER stress response; dysregulation linked to disease.", "protein": "ATF6", "relationship_type": "causal", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Lassa Fever", "glycan_involvement": "Acts on glycoprotein processing.", "mechanism": "Engineered \u03b11-antitrypsin RRVL inhibits SKI-1/S1P, blocking GPC maturation and viral spread.", "protein": "\u03b11-antitrypsin RRVL mutant", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Lassa Fever", "glycan_involvement": "Inhibits glycoprotein processing.", "mechanism": "PF-429242 inhibits SKI-1/S1P, blocking GPC maturation and arenavirus infectivity.", "protein": "PF-429242", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7121819" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Binds sialylated/fucosylated glycans (e.g., sialyl Lewis X) on leukocyte glycoproteins.", "mechanism": "Upregulated on activated endothelium, mediates leukocyte adhesion and rolling, gene polymorphisms linked to accelerated disease.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Myocardial Infarction (MI)", "glycan_involvement": "Interacts with PSGL-1 (mucin-type O-glycosylated ligand) on leukocytes.", "mechanism": "Elevated on activated platelets/endothelium, mediates platelet-leukocyte aggregates, upregulates tissue factor and cytokines.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Ischemic Stroke", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "Upregulated in cerebral ischemia, mediates firm leukocyte adhesion and transmigration.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Bronchial Asthma", "glycan_involvement": "N-glycosylation modulates ligand binding and stability.", "mechanism": "Promotes eosinophil recruitment to airway, upregulated prior to asthma attacks.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Ligand binding depends on glycan recognition (sialyl Lewis X).", "mechanism": "Serum levels correlate with blood pressure; gene polymorphisms (Leu554Phe, Ser128Arg) linked to disease severity.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "Binds O-glycosylated PSGL-1 and sulfatides on platelets.", "mechanism": "Elevated in blood of CAD patients, mediates platelet aggregation and leukocyte recruitment.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Atopic Dermatitis", "glycan_involvement": "Recognizes CLA (sialyl 6-sulfo LeX) on T cells.", "mechanism": "Highly expressed on vascular endothelium in lesions, mediates T cell recruitment.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7121831" }, { "confidence": "medium", "disease": "Bullous Pemphigoid", "glycan_involvement": "Binds mucin-type O-glycosylated ligands on endothelium.", "mechanism": "Expressed on skin leukocytes, mediates leukocyte infiltration and destruction of basement membrane zone.", "protein": "L-selectin", "protein_enriched": { "function": "Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells (PubMed:12403782, PubMed:28011641, PubMed:28489325). Mediates the adherence of lymphocytes to endo", "gene_name": "SELL", "glycan_count": 52, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06247RL", "G45395BF", "G56518TU", "G57776ZS", "G70232NH", "G90382BL", "G91473PK", "G03382KH", "G17689DH", "G17893UF", "G20425TQ", "G22310AV", "G23863VK", "G27716UU", "G28948UC", "G29857RC", "G30769VJ", "G31544HA", "G33791AF", "G35291GU", "G36191CD", "G40966IE", "G44215PV", "G44444MB", "G45359RY", "G46626CC", "G47058MH", "G48381WH", "G50045TK", "G52567OL", "G55373ZG", "G60288TK", "G60660BN", "G61244WO", "G63889NK", "G66163OV", "G68442BQ", "G68796US", "G72797UR", "G74741QU", "G75983OB", "G78059CC", "G78374AB", "G84452RH", "G84820NF", "G86357DX", "G86795LJ", "G89098OM", "G90093AU", "G96170OK", "G97268YK", "G97823BP" ], "uniprot_id": "P14151" }, "relationship_type": "causal", "source_pmcid": "PMC7121831" }, { "confidence": "medium", "disease": "Coronary Artery Disease (CAD)", "glycan_involvement": "N-glycosylation affects dimerization and function.", "mechanism": "Soluble PECAM-1 levels and gene polymorphisms (Leu125Val) associated with severe coronary artery stenosis.", "protein": "PECAM-1", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for eff", "gene_name": "Pecam1", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G25079LO", "G24748EV", "G15664MX", "G72747WU", "G31986NC", "G80920RR", "G49108TO" ], "uniprot_id": "Q08481" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus (T1DM)", "glycan_involvement": "Ligand binding via glycan recognition.", "mechanism": "Elevated sE-selectin is an early marker of endothelial dysfunction and risk for atherosclerosis in T1DM children.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC7121831" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "MBL recognizes glycosylated apoptotic cells; deficiency impairs clearance", "mechanism": "MBL deficiency predisposes to SLE and aggravates disease progression, increases risk of complications (e.g., arterial thrombosis, infections)", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Rheumatoid Arthritis (RA)", "glycan_involvement": "MBL binds glycosylated ligands on immune cells, modulates inflammation", "mechanism": "Low MBL levels associated with increased severity, poor prognosis, and early erosive RA", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Sepsis/Systemic Inflammatory Response Syndrome (SIRS)", "glycan_involvement": "MBL binds pathogen glycans, activates complement", "mechanism": "MBL deficiency increases risk and severity of sepsis/SIRS, progression to septic shock", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Vulvovaginal Candidiasis", "glycan_involvement": "MBL binds fungal cell wall glycans (mannose/fucose)", "mechanism": "MBL deficiency increases susceptibility; higher MBL levels protective", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "medium", "disease": "Gestational Diabetes Mellitus (GDM)", "glycan_involvement": "MBL glycosylation status affects immune modulation in pregnancy", "mechanism": "MBL gene G54D mutation associated with increased risk of GDM and heavier infants", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7122001" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "MBL involved in immune recognition of glycosylated targets during early development", "mechanism": "Low-level MBL genotypes associated with increased risk of childhood ALL, especially early onset", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "medium", "disease": "Hepatitis B Virus Infection", "glycan_involvement": "MBL binds viral envelope glycans, modulates immune clearance", "mechanism": "MBL codon 52 mutation associated with persistent HBV infection in Caucasians", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Hepatitis C Virus Infection", "glycan_involvement": "MBL binds high-mannose N-glycans on HCV E2 glycoprotein", "mechanism": "MBL genotype influences elimination of HCV during interferon therapy; high-mannose N-glycans on HCV E2 bind MBL", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "MBL binds viral glycosylated envelope proteins", "mechanism": "MBL deficiency increases susceptibility to SARS-CoV infection; MBL binds virus and activates complement", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/protective", "source_pmcid": "PMC7122001" }, { "confidence": "medium", "disease": "Human T-cell Lymphotropic Virus (HTLV) Infection", "glycan_involvement": "MBL binds viral glycoproteins", "mechanism": "MBL BB genotype associated with increased susceptibility to HTLV infection", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7122001" }, { "confidence": "high", "disease": "Acquired Immunodeficiency Syndrome (AIDS)", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes from immune recognition and are essential for receptor binding.", "mechanism": "gp120 binds CD4 and chemokine receptors to mediate HIV entry into host cells, leading to immune cell depletion.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "Acquired Immunodeficiency Syndrome (AIDS)", "glycan_involvement": "Glycosylation affects gp41 structure and immune evasion.", "mechanism": "gp41 mediates fusion of viral and host membranes after gp120-CD4 binding.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "Opportunistic infections (e.g., Pneumocystis carinii pneumonia)", "glycan_involvement": "Glycans on gp120 contribute to immune evasion, facilitating chronic infection.", "mechanism": "gp120-mediated HIV infection leads to CD4+ T cell depletion, increasing susceptibility to opportunistic infections.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "medium", "disease": "HIV-associated dementia", "glycan_involvement": "Glycosylation modulates neurotoxicity and immune recognition.", "mechanism": "gp120 interaction with CNS cells contributes to neuropathology.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycans on E1 are critical for proper folding, viral infectivity, and immune evasion.", "mechanism": "E1 glycoprotein mediates HCV entry into hepatocytes.", "protein": "HCV E1", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycans on E2 shield neutralizing epitopes and modulate receptor binding.", "mechanism": "E2 glycoprotein binds to host receptors for viral entry.", "protein": "HCV E2", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Not a glycoprotein, but detected by anti-core antibodies in diagnostic assays.", "mechanism": "Core antigen is detected in blood as a marker of HCV infection.", "protein": "HCV core protein", "relationship_type": "biomarker", "source_pmcid": "PMC7122038" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation of E1/E2 contributes to persistent infection and immune evasion.", "mechanism": "Chronic infection mediated by E1/E2 leads to liver fibrosis and cirrhosis.", "protein": "HCV E1/E2", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation aids in immune evasion, promoting chronicity and oncogenesis.", "mechanism": "Chronic HCV infection increases risk of HCC.", "protein": "HCV E1/E2", "relationship_type": "causal", "source_pmcid": "PMC7122038" }, { "confidence": "medium", "disease": "HIV drug resistance", "glycan_involvement": "Altered glycosylation patterns can affect drug binding and resistance.", "mechanism": "Mutations in gp120 can confer resistance to entry inhibitors.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122038" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Extensive N-glycosylation shields epitopes, modulates immune recognition.", "mechanism": "Mediates viral entry by binding CD4 and coreceptors, facilitating membrane fusion.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC7122156" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "N-glycosylation affects fusogenic activity and immune evasion.", "mechanism": "Drives membrane fusion between viral and host membranes.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122156" }, { "confidence": "high", "disease": "Bovine Viral Diarrhea", "glycan_involvement": "N-glycosylation modulates receptor binding and antigenicity.", "mechanism": "Major envelope glycoprotein mediating viral attachment and entry.", "protein": "BVDV E2", "protein_enriched": { "function": "Acts as a cofactor for the NS3 protease activity", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q65815" }, "relationship_type": "causal", "source_pmcid": "PMC7122156" }, { "confidence": "high", "disease": "Encephalitis (Semliki Forest Virus)", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Fusion glycoprotein responsible for membrane fusion and viral entry.", "protein": "Semliki Forest Virus E1", "relationship_type": "causal", "source_pmcid": "PMC7122156" }, { "confidence": "medium", "disease": "Encephalitis (Semliki Forest Virus)", "glycan_involvement": "N-glycosylation influences antigenicity and host range.", "mechanism": "Envelope glycoprotein involved in receptor binding and viral entry.", "protein": "Semliki Forest Virus E2", "relationship_type": "causal", "source_pmcid": "PMC7122156" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APN is a membrane-bound glycoprotein; glycosylation affects stability and localization.", "mechanism": "Reduced APN activity in CSF of AD patients; altered peptide metabolism.", "protein": "Aminopeptidase N (APN)", "relationship_type": "biomarker", "source_pmcid": "PMC7122168" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "PSA is a glycoprotein; glycosylation may affect cellular localization.", "mechanism": "PSA-positive reactive microglia associated with senile plaques and neurofibrillary tangles.", "protein": "Puromycin-sensitive aminopeptidase (PSA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7122168" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "NEP is a cell-surface glycoprotein; glycosylation required for activity and trafficking.", "mechanism": "Decreased NEP activity leads to impaired amyloid \u03b2 degradation and plaque accumulation.", "protein": "Endopeptidase 24.11 (Neprilysin, NEP)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7122168" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "ACE is a glycoprotein; glycosylation affects enzyme function.", "mechanism": "ACE gene polymorphisms associated with increased AD risk; ACE degrades amyloid \u03b2.", "protein": "Angiotensin-converting enzyme (ACE)", "relationship_type": "genetic risk/biomarker", "source_pmcid": "PMC7122168" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "CPE is glycosylated; glycosylation affects sorting and activity.", "mechanism": "Decreased neuronal expression and altered localization in AD brains; involved in APP processing.", "protein": "Carboxypeptidase E/H (CPE)", "relationship_type": "biomarker", "source_pmcid": "PMC7122168" }, { "confidence": "high", "disease": "Late infantile neuronal ceroid lipofuscinosis (CLN2)", "glycan_involvement": "TPP-I is glycosylated; glycosylation required for lysosomal targeting.", "mechanism": "TPP-I mutations cause lysosomal storage and neuronal death.", "protein": "Tripeptidyl peptidase I (TPP-I)", "relationship_type": "causal", "source_pmcid": "PMC7122168" }, { "confidence": "medium", "disease": "Schizophrenia", "glycan_involvement": "PSA glycosylation may affect brain distribution.", "mechanism": "Reduced PSA levels in multiple brain regions of schizophrenia patients.", "protein": "Puromycin-sensitive aminopeptidase (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC7122168" }, { "confidence": "medium", "disease": "Experimental allergic encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation affects APN's cell-surface expression.", "mechanism": "APN degrades enkephalins; inhibitors have anti-inflammatory and neuroprotective effects.", "protein": "Aminopeptidase N (APN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122168" }, { "confidence": "low", "disease": "Amyotrophic lateral sclerosis", "glycan_involvement": "PTP is a glycoprotein; glycosylation may affect activity.", "mechanism": "TRH (processed by PTP) improves neurological symptoms in some ALS patients.", "protein": "Prohormone thiol protease (PTP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122168" }, { "confidence": "medium", "disease": "Multiple system atrophy", "glycan_involvement": "CD13 glycosylation affects immune and neural functions.", "mechanism": "APN/CD13 involved in neuropeptide metabolism; altered activity in neurodegeneration.", "protein": "CD13 (APN)", "relationship_type": "biomarker", "source_pmcid": "PMC7122168" }, { "confidence": "high", "disease": "Highly Pathogenic Avian Influenza", "glycan_involvement": "Glycosylation affects HA folding and accessibility of cleavage site.", "mechanism": "Furin-mediated cleavage of HA glycoprotein enables viral fusion and systemic spread.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates Env structure and immune evasion.", "mechanism": "Furin and PC7 cleave Env glycoprotein, activating fusion for viral entry.", "protein": "HIV-1 Env", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "Glycosylation influences F protein folding and cleavage efficiency.", "mechanism": "Furin cleaves F glycoprotein, enabling membrane fusion and infection.", "protein": "Fusion (F) protein (RSV, NDV, Measles)", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation shields GP from immune recognition.", "mechanism": "Furin cleaves GP, activating fusion for viral entry.", "protein": "Ebola Virus Glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Lassa Fever", "glycan_involvement": "Glycosylation affects GP processing and immune evasion.", "mechanism": "SKI-1/S1P cleaves GP, activating fusion for viral entry.", "protein": "Lassa Virus Glycoprotein (GP)", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation required for proper folding and trafficking.", "mechanism": "Defective PC1/3 or PC2 cleavage leads to hyperproinsulinemia and impaired insulin production.", "protein": "Proinsulin", "relationship_type": "biomarker", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Von Willebrand Disease", "glycan_involvement": "Glycosylation essential for secretion and multimerization.", "mechanism": "Furin, PACE4, and PC7 cleave precursor; defective processing leads to bleeding disorder.", "protein": "Von Willebrand Factor", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "medium", "disease": "Anthrax", "glycan_involvement": "Glycosylation may affect toxin stability and host interaction.", "mechanism": "Furin and PACE4 cleave protective antigen, activating toxin.", "protein": "Anthrax Toxin Protective Antigen", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q4W9A7" }, "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Autosomal Dominant Hypercholesterolemia (ADH)", "glycan_involvement": "Glycosylation affects PCSK9 secretion and receptor binding.", "mechanism": "PCSK9 regulates LDL receptor degradation; gain-of-function mutations cause ADH.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7122180" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for receptor maturation and function.", "mechanism": "PC5A cleaves insulin receptor precursor; defective processing impairs glucose homeostasis.", "protein": "Insulin Receptor", "relationship_type": "causal", "source_pmcid": "PMC7122180" }, { "confidence": "high", "disease": "Wilson Disease", "glycan_involvement": "Ceruloplasmin is a glycoprotein; glycosylation is required for its stability and secretion.", "mechanism": "Low ceruloplasmin is used as a diagnostic marker for Wilson disease, reflecting impaired copper transport.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation is essential for secretion and function.", "mechanism": "Reduced synthesis in ALF leads to impaired coagulation and bleeding risk.", "protein": "Coagulation Factor V", "protein_enriched": { "function": "Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin", "gene_name": "F5", "glycan_count": 77, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G00031MO", "G10225UW", "G29931IJ", "G57321FI", "G74722FL", "G39558MO", "G43417UB", "G81006GJ", "G22140GZ", "G50045TK", "G72291OX", "G53434XO", "G63628AV", "G29068FM", "G27391WQ", "G58001LT", "G23294PN", "G82463GQ", "G84452RH", "G49108TO", "G00912UN", "G22310AV", "G35029YA", "G56784JY", "G62765YT", "G70418MS", "G78790NZ", "G91473PK", "G48414YA", "G57888GL", "G62461SM", "G04854VP", "G05933EN", "G06356OH", "G49644CL", "G31433PN", "G39595FH", "G35305EF", "G37881RL", "G55383ZG", "G81263BG", "G99966GV", "G08606CV", "G15169WU", "G23453IV", "G31916IQ", "G57776ZU", "G00033MO", "G32550BI", "G03382KH", "G06110VR", "G10256JP", "G25451PN", "G25637MV", "G29880MM", "G34730YF", "G51895WL", "G55220VL", "G82119TF", "G84820NF", "G98205FV", "G99858XP", "G47748JZ", "G59626AS", "G05724UK", "G39188ZX", "G72735IY", "G80966KZ", "G27993JQ", "G33791AF", "G34617SM", "G41882MT", "G50757KG", "G66760KM", "G72667IM", "G93656SY", "G08918WF" ], "uniprot_id": "P12259" }, "relationship_type": "causal", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation required for stability and activity.", "mechanism": "Deficiency due to liver failure causes prolonged INR and bleeding.", "protein": "Coagulation Factor VII", "protein_enriched": { "function": "Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or t", "gene_name": "F7", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G71142DF", "G84224TW", "G82576YO", "G96881BQ", "G06215XQ", "G08146BT", "G23695IQ", "G35061TJ", "G42358LZ", "G50739NP", "G71527NE", "G75494EI", "G91130VE", "G00912UN", "G08918WF", "G40574BA", "G43669FQ", "G45395BF" ], "uniprot_id": "P08709" }, "relationship_type": "causal", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation affects plasma half-life.", "mechanism": "Decreased synthesis in ALF contributes to bleeding diathesis.", "protein": "Coagulation Factor IX", "protein_enriched": { "function": "Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipid", "gene_name": "F9", "glycan_count": 37, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27608TI", "G50236GJ", "G70593HA", "G76163CP", "G96881BQ", "G10651WD", "G45637XA", "G70649KP", "G81006GJ", "G29068FM", "G43417UB", "G18717LR", "G74722FL", "G57321FI", "G10008NR", "G12743GW", "G12793SR", "G15016TE", "G15169WU", "G17827EU", "G28847IN", "G31639NG", "G32551IQ", "G38277AO", "G39595FH", "G47518TP", "G48414YA", "G52527GH", "G58489ZK", "G66088HZ", "G69834CE", "G74815GQ", "G79318PG", "G86904UH", "G87108ET", "G92975MH", "G98725UL" ], "uniprot_id": "P00740" }, "relationship_type": "causal", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Reduced levels in ALF impair coagulation cascade.", "protein": "Coagulation Factor X", "protein_enriched": { "function": "Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting (PubMed:22409427). Factor Xa activate", "gene_name": "F10", "glycan_count": 35, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G43417UB", "G53434XO", "G06356OH", "G18938DW", "G20425TQ", "G23863VK", "G24501HF", "G29857RC", "G32854GF", "G36191CD", "G41882MT", "G45359RY", "G46568MX", "G47012YE", "G49478NM", "G50045TK", "G59536GA", "G68866GS", "G72797UR", "G73073LQ", "G75850OP", "G78059CC", "G79809MM", "G81263BG", "G84452RH", "G85678WN", "G87123QX", "G88068QT", "G91365ZQ", "G00912UN", "G11314AS", "G57321FI", "G49108TO", "G80111QD", "G81006GJ" ], "uniprot_id": "P00742" }, "relationship_type": "causal", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation critical for secretion and clot formation.", "mechanism": "Low fibrinogen in ALF/HELLP/AFLP leads to bleeding risk.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC7122204" }, { "confidence": "medium", "disease": "Malignancy-associated Hepatic Failure", "glycan_involvement": "Glycosylation affects enzyme activity and serum levels.", "mechanism": "Elevated in hepatic infiltration by malignancy.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122204" }, { "confidence": "medium", "disease": "Malignancy-associated Hepatic Failure", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Elevated in cholestasis and hepatic infiltration.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122204" }, { "confidence": "medium", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "N-glycosylation affects serum half-life and function.", "mechanism": "Serum transferrin may decrease in ALF due to impaired synthesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122204" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "Glycosylation modulates immune function and clearance.", "mechanism": "Elevated serum immunoglobulins are a diagnostic marker for autoimmune hepatitis.", "protein": "Immunoglobulins (IgG, IgM)", "relationship_type": "biomarker", "source_pmcid": "PMC7122204" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry via sialic acid binding; detected by LAMP for diagnosis.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and antigenicity.", "mechanism": "NA cleaves sialic acids to facilitate viral release; target for antivirals.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122297" }, { "confidence": "high", "disease": "Japanese Encephalitis", "glycan_involvement": "N-glycosylation influences neuroinvasiveness and immune response.", "mechanism": "E protein is essential for viral entry and fusion; targeted in LAMP assays.", "protein": "Envelope glycoprotein E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "medium", "disease": "Rift Valley Fever", "glycan_involvement": "N-glycosylation required for proper folding and infectivity.", "mechanism": "GN/GC mediate host cell attachment and fusion; detected by LAMP.", "protein": "Envelope glycoprotein GN/GC", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Limited glycosylation; mainly structural role.", "mechanism": "Matrix protein is a conserved antigen; used for subtype-specific LAMP detection.", "protein": "Matrix protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "medium", "disease": "Hand-Foot-and-Mouth Disease", "glycan_involvement": "Potential O-glycosylation affects capsid stability.", "mechanism": "VP3 is a capsid protein; LAMP targets VP3 gene for EV71 detection.", "protein": "VP3 protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "low", "disease": "Duck Virus Enteritis", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "UL6 is involved in viral DNA packaging; LAMP targets UL6 for diagnosis.", "protein": "UL6 protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "O-glycosylation modulates immune recognition.", "mechanism": "N protein is abundant and conserved; LAMP targets nucleocapsid gene for SARS-CoV detection.", "protein": "Nucleocapsid protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "medium", "disease": "Porcine Circovirus Disease (PMWS/PDNS)", "glycan_involvement": "Limited glycosylation; mainly functional for replication.", "mechanism": "Rep protein is essential for viral replication; LAMP targets ORF2 for PCV2 detection.", "protein": "ORF2 Rep protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "high", "disease": "West Nile Fever", "glycan_involvement": "N-glycosylation modulates neuroinvasiveness and immune evasion.", "mechanism": "Envelope protein mediates viral entry; LAMP targets envelope gene for diagnosis.", "protein": "Envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122297" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "CRP is a glycoprotein; glycosylation is required for stability and function.", "mechanism": "CRP is upregulated in response to inflammation, correlates with disease activity, especially in Crohn's disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Highly glycosylated; glycan structures modulate anti-inflammatory properties.", "mechanism": "Levels correlate with disease activity but long half-life limits clinical utility.", "protein": "Orosomucoid (Alpha-1-acid glycoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "N-glycosylation affects stability and antimicrobial activity.", "mechanism": "Fecal lactoferrin increases with neutrophil infiltration and inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MOG is glycosylated; glycan moieties may affect antigenicity.", "mechanism": "Autoantibodies to MOG are studied as markers and possible contributors to demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7122305" }, { "confidence": "high", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "MAG is sialylated; glycan structures are key for antibody recognition.", "mechanism": "IgM antineural antibodies to MAG are predictive of immune-mediated neuropathy.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)/Liver Cirrhosis", "glycan_involvement": "Adiponectin is O-glycosylated; glycosylation modulates secretion and bioactivity.", "mechanism": "High adiponectin levels associated with increased risk of hepatocellular carcinoma.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "high", "disease": "Crohn's Disease (CD)", "glycan_involvement": "Mannan is a glycoprotein; glycan epitopes are the antibody target.", "mechanism": "ASCA targets mannan glycoprotein in yeast cell wall; high titers are specific for CD.", "protein": "Anti-Saccharomyces cerevisiae antibody (ASCA) target: Mannan (PPM)", "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "medium", "disease": "Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)", "glycan_involvement": "Glycosylation affects cell adhesion and immune recognition.", "mechanism": "Alterations in TAG-1 may help guide therapy and monitor response to IVIG.", "protein": "TAG-1 (Transient axonal glycoprotein-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "low", "disease": "Psoriasis", "glycan_involvement": "N-glycosylation modulates function and immune interactions.", "mechanism": "Lactoferrin's antimicrobial and immunomodulatory properties may reflect skin inflammation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "medium", "disease": "Liver Cirrhosis", "glycan_involvement": "N-glycosylation changes reflect liver synthetic function.", "mechanism": "Altered glycosylation patterns of transferrin are used in noninvasive fibrosis panels (e.g., FibroTest).", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122305" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Furin is a glycoprotein; glycosylation affects its trafficking and activity.", "mechanism": "Furin activates growth factors and matrix metalloproteinases, promoting tumor progression.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122317" }, { "confidence": "high", "disease": "Autosomal dominant hypercholesterolemia", "glycan_involvement": "Glycosylation modulates PCSK9 secretion and function.", "mechanism": "PCSK9 regulates LDL receptor degradation, leading to increased cholesterol levels.", "protein": "PCSK9 (NARC-1)", "relationship_type": "causal", "source_pmcid": "PMC7122317" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation influences SKI-1/S1P maturation and activity.", "mechanism": "SKI-1/S1P processes SREBP, affecting lipid and glucose metabolism.", "protein": "SKI-1/S1P", "relationship_type": "causal", "source_pmcid": "PMC7122317" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "PACE4 glycosylation impacts its stability and localization.", "mechanism": "PACE4 activates pro-tumorigenic substrates, facilitating tumor growth and invasion.", "protein": "PACE4", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122317" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation required for PC1 folding and activity.", "mechanism": "PC1 processes prohormones involved in appetite regulation.", "protein": "PC1", "relationship_type": "causal", "source_pmcid": "PMC7122317" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation modulates PC2 stability and secretion.", "mechanism": "PC2 processes proinsulin, affecting insulin production.", "protein": "PC2", "relationship_type": "causal", "source_pmcid": "PMC7122317" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation affects PC5 activity and cellular localization.", "mechanism": "PC5 activates substrates involved in cell migration and invasion.", "protein": "PC5", "protein_enriched": { "function": "Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive and regulated secretory ", "gene_name": "PCSK5", "glycan_count": 2, "glycosylation_sites_count": 12, "glytoucan_ids": [ "G62765YT", "G80920RR" ], "uniprot_id": "Q92824" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122317" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation influences PC7 trafficking and activity.", "mechanism": "PC7 processes neuropeptide precursors, impacting neuronal function.", "protein": "PC7", "relationship_type": "causal", "source_pmcid": "PMC7122317" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation required for \u03b11-PDX inhibitory function.", "mechanism": "\u03b11-PDX inhibits Furin, reducing activation of pro-tumorigenic factors.", "protein": "\u03b11-PDX", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122317" }, { "confidence": "low", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation stabilizes 7B2 structure and function.", "mechanism": "7B2 acts as a chaperone for PC2, preventing aggregation and dysfunction.", "protein": "7B2", "relationship_type": "protective", "source_pmcid": "PMC7122317" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation shields S protein from neutralizing antibodies and affects receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding and requires proteolytic activation for infectivity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation modulates receptor interaction and immune evasion.", "mechanism": "Mediates viral entry via DPP4 binding and requires proteolytic activation for infectivity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Indirect; S protein glycosylation may affect protease accessibility.", "mechanism": "Activates S protein in endosomes, enabling viral fusion and entry.", "protein": "Cathepsin L", "protein_enriched": { "function": "Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone r", "gene_name": "CTSL", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G06110VR", "G06356OH", "G14669DU", "G22310AV", "G28681TP", "G31665QC", "G31852PQ", "G37881RL", "G39188ZX", "G41247ZX", "G43089EG", "G47518TP", "G48414YA", "G49589RB", "G50282JC", "G52527GH", "G62765YT", "G71784JC", "G75983OB", "G80920RR", "G92050GC", "G92275SC", "G96091TT" ], "uniprot_id": "P07711" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Indirect; S protein glycosylation may modulate cleavage efficiency.", "mechanism": "Activates S protein at cell surface, essential for viral spread in respiratory epithelium.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation near cleavage sites may regulate furin accessibility.", "mechanism": "Pre-cleaves S protein at S1/S2 site in secretory pathway, enabling subsequent activation by TMPRSS2.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation at ACE2 N82 blocks S protein interaction in rats.", "mechanism": "Serves as entry receptor for SARS-CoV via S protein binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation in rodent DPP4 blocks MERS-S interaction.", "mechanism": "Serves as entry receptor for MERS-CoV via S protein binding.", "protein": "DPP4", "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "medium", "disease": "PED", "glycan_involvement": "N-glycosylation modulates infectivity and immune evasion.", "mechanism": "Mediates viral entry into porcine intestinal cells; furin motif insertion increases infectivity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "medium", "disease": "Common Cold", "glycan_involvement": "Likely glycosylated; modulates function.", "mechanism": "Promotes release of virus from infected cells in some betacoronaviruses.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Indirect; glycosylation of HA may affect cleavage.", "mechanism": "Activates hemagglutinin for viral entry and spread.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122371" }, { "confidence": "high", "disease": "Infectious bronchitis in chickens", "glycan_involvement": "N-linked glycosylation is essential for proper folding, receptor binding, and immune evasion.", "mechanism": "Mediates viral entry via receptor binding and membrane fusion; determines host and tissue tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "high", "disease": "Respiratory distress", "glycan_involvement": "Glycosylation affects receptor binding specificity and immune recognition.", "mechanism": "S1 domain binds to \u03b1-2,3-linked sialic acid on respiratory epithelial cells, initiating infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Nephritis (interstitial nephritis)", "glycan_involvement": "Glycosylation modulates tissue tropism and immune escape.", "mechanism": "Certain S1 variants enable kidney tropism and nephropathogenicity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Decreased egg production/quality", "glycan_involvement": "Glycosylation influences S protein antigenicity and tissue targeting.", "mechanism": "Infection of oviduct via S protein leads to reproductive tract lesions and reduced egg output.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "high", "disease": "Infectious bronchitis in chickens", "glycan_involvement": "N-linked glycosylation required for proper membrane integration and function.", "mechanism": "Essential for virus assembly and budding; interacts with S and N proteins.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Infectious bronchitis in chickens", "glycan_involvement": "No direct glycosylation reported; interacts with glycoproteins for assembly.", "mechanism": "Required for viral assembly, budding, and pathogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "high", "disease": "Vaccine escape and emergence of new IBV strains", "glycan_involvement": "Altered glycosylation patterns contribute to immune evasion.", "mechanism": "Antigenic variation in S1 (including glycosylation sites) leads to poor cross-protection and vaccine escape.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Oviduct lesions", "glycan_involvement": "Glycosylation affects tissue tropism.", "mechanism": "Mediates infection of oviduct epithelial cells, causing lesions and reproductive dysfunction.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Infectious bronchitis in chickens", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Induces cytotoxic T cell responses and is used in diagnostic assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122401" }, { "confidence": "medium", "disease": "Proventriculitis", "glycan_involvement": "Glycosylation may influence tissue specificity.", "mechanism": "Certain IBV strains with S protein variants infect proventriculus, causing lesions.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122401" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Not specified.", "mechanism": "Overexpression and gene fusion with ERG drive cancer progression and metastasis.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "Influenza virus infection", "glycan_involvement": "Cleaves glycosylated hemagglutinin.", "mechanism": "Essential for proteolytic activation of influenza hemagglutinin, enabling viral spread.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "SARS/MERS coronavirus infection", "glycan_involvement": "Spike protein is glycosylated; cleavage required for fusion.", "mechanism": "Activates coronavirus spike glycoprotein, facilitating viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "medium", "disease": "Esophageal squamous cell carcinoma", "glycan_involvement": "Not specified.", "mechanism": "Downregulation associated with cancer; promotes apoptosis via EGFR/AKT pathway.", "protein": "DESC1 (TMPRSS11E)", "protein_enriched": { "function": "May play a role in hearing", "gene_name": "TMPRSS5", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9H3S3" }, "relationship_type": "protective/tumor suppressor", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "Deafness", "glycan_involvement": "Not specified.", "mechanism": "Mutations disrupt protease activity, leading to hair cell degeneration.", "protein": "TMPRSS3", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity (PubMed:24434139). Seems to be capable of activating ENaC (B", "gene_name": "TMPRSS4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9NRS4" }, "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "medium", "disease": "Deafness", "glycan_involvement": "Not specified.", "mechanism": "Knockout causes cochlear defects and hearing loss in mice.", "protein": "Hepsin (TMPRSS1)", "protein_enriched": { "function": "Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:15839837, PubMed:21875933). Plays a role in ce", "gene_name": "HPN", "glycan_count": 13, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G01650EU", "G18647XP", "G27058EU", "G41071NU", "G42124LM", "G47644PP", "G62765YT", "G63041LO", "G65184UU", "G80920RR", "G87661QW", "G90659AW", "G92275SC" ], "uniprot_id": "P05981" }, "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "medium", "disease": "Chronic airway diseases (asthma, bronchitis)", "glycan_involvement": "Not specified.", "mechanism": "Elevated in sputum of patients; modulates inflammation via PAR-2 activation.", "protein": "HAT (TMPRSS11D)", "relationship_type": "biomarker", "source_pmcid": "PMC7122464" }, { "confidence": "medium", "disease": "Psoriasis vulgaris", "glycan_involvement": "Not specified.", "mechanism": "Upregulated in lesions; promotes IL-8 production and inflammation.", "protein": "HAT (TMPRSS11D)", "relationship_type": "biomarker", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "Iron-refractory iron-deficiency anemia (IRIDA)", "glycan_involvement": "Not specified.", "mechanism": "Deficiency increases hepcidin, causing IRIDA.", "protein": "Matriptase-2 (TMPRSS6)", "protein_enriched": { "function": "Membrane-bound serine protease (PubMed:18976966, PubMed:20518742, PubMed:25156943, PubMed:25588876). Through the cleavage of cell surface hemojuvelin (HJV), a regulator of the expression of the iron a", "gene_name": "TMPRSS6", "glycan_count": 0, "glycosylation_sites_count": 7, "glytoucan_ids": [], "uniprot_id": "Q8IU80" }, "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "Congenital enteropeptidase deficiency", "glycan_involvement": "N-glycosylation required for apical delivery.", "mechanism": "Loss-of-function mutations cause severe intestinal malabsorption.", "protein": "Enteropeptidase (PRSS7)", "relationship_type": "causal", "source_pmcid": "PMC7122464" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation shields epitopes, modulates immune recognition and fusion activity.", "mechanism": "Mediates viral entry via membrane fusion; target for entry inhibitors (e.g., Enfuvirtide) and vaccine development.", "protein": "HIV-1 envelope glycoprotein (Env, gp120/gp41)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "N-glycosylation affects antigenicity, receptor binding, and fusion efficiency.", "mechanism": "Mediates viral entry by binding host receptors and catalyzing membrane fusion; target for antivirals (e.g., Arbidol) and vaccines.", "protein": "Influenza A hemagglutinin (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Proton channel essential for viral uncoating and maturation; target of amantadine/rimantadine.", "protein": "Influenza A matrix protein 2 (M2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "high", "disease": "Influenza (Flu)", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Proton channel required for viral assembly and maturation; not inhibited by adamantanes.", "protein": "Influenza B matrix protein 2 (BM2)", "protein_enriched": { "function": "RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their capping and polyadenylation. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N).", "gene_name": "L", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QJT4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Cation channel required for virus assembly and release; target for channel inhibitors (e.g., rimantadine).", "protein": "Hepatitis C virus p7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Viroporin activity facilitates virus release and modulates host cell environment.", "protein": "HIV-1 Vpu", "relationship_type": "causal", "source_pmcid": "PMC7122571" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "N-glycosylation modulates immune recognition and fusion activity.", "mechanism": "Class II fusion glycoprotein mediates viral entry via membrane fusion; target for neutralizing antibodies.", "protein": "Dengue virus E protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122571" }, { "confidence": "medium", "disease": "Vesicular stomatitis (not listed in diseases above, but implied)", "glycan_involvement": "N-glycosylation affects folding and function.", "mechanism": "Class III fusion glycoprotein mediates viral entry via membrane fusion.", "protein": "Vesicular stomatitis virus G protein (VSV G)", "relationship_type": "causal", "source_pmcid": "PMC7122571" }, { "confidence": "medium", "disease": "Herpes simplex", "glycan_involvement": "N-glycosylation modulates immune evasion and fusion activity.", "mechanism": "Class III fusion glycoprotein required for membrane fusion and viral entry.", "protein": "Herpes simplex virus gB", "relationship_type": "causal", "source_pmcid": "PMC7122571" }, { "confidence": "medium", "disease": "Epstein-Barr virus infection", "glycan_involvement": "N-glycosylation modulates function and immune recognition.", "mechanism": "Class III fusion glycoprotein mediates membrane fusion for viral entry.", "protein": "Epstein-Barr virus gB", "relationship_type": "causal", "source_pmcid": "PMC7122571" }, { "confidence": "medium", "disease": "Immune dysfunction/infection", "glycan_involvement": "Arabinogalactan glycan backbone is essential for activity", "mechanism": "Enhances phagocytosis, stimulating immune response", "protein": "Glycyrrhizan GA (arabinogalactan protein)", "relationship_type": "protective", "source_pmcid": "PMC7122586" }, { "confidence": "medium", "disease": "Immune dysfunction/infection", "glycan_involvement": "Glycosylation (glucuronic acid residues) required for function", "mechanism": "Immunomodulatory effects, anti-inflammatory activity", "protein": "Glycyrrhizin", "relationship_type": "protective", "source_pmcid": "PMC7122586" }, { "confidence": "low", "disease": "HIV infection", "glycan_involvement": "Glycosylation critical for solubility and bioactivity", "mechanism": "Reported anti-HIV activity (via phenolic constituents in licorice)", "protein": "Glycyrrhizin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122586" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects receptor localization and function.", "mechanism": "Mediates vasoconstriction; antagonists lower blood pressure.", "protein": "\u03b11-adrenoceptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates receptor signaling.", "mechanism": "Presynaptic inhibition of norepinephrine release; agonists (e.g., clonidine) reduce sympathetic tone.", "protein": "\u03b12-adrenoceptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "Stimulation increases cardiac rate and force; antagonists (beta-blockers) reduce cardiac workload.", "protein": "\u03b21-adrenoceptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Glycosylation influences ligand binding and receptor stability.", "mechanism": "Mediates bronchodilation; agonists relieve bronchoconstriction.", "protein": "\u03b22-adrenoceptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation affects receptor activity.", "mechanism": "Regulates lipolysis and thermogenesis in adipose tissue.", "protein": "\u03b23-adrenoceptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Likely glycosylated; glycan status may affect ligand binding.", "mechanism": "Mediates central hypotensive effects of clonidine-like drugs.", "protein": "Imidazoline receptor (I1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122603" }, { "confidence": "low", "disease": "Ischemia", "glycan_involvement": "Glycosylation may influence mitochondrial localization.", "mechanism": "Involved in neuroprotection during cerebral ischemia.", "protein": "Imidazoline receptor (I2)", "relationship_type": "protective", "source_pmcid": "PMC7122603" }, { "confidence": "medium", "disease": "Arrhythmia", "glycan_involvement": "N-glycosylation modulates receptor desensitization.", "mechanism": "Overstimulation increases risk of arrhythmias.", "protein": "\u03b21-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC7122603" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects receptor downregulation.", "mechanism": "Chronic stimulation may contribute to cardiac remodeling.", "protein": "\u03b22-adrenoceptor", "relationship_type": "causal", "source_pmcid": "PMC7122603" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation modulates receptor function.", "mechanism": "Inhibits excessive sympathetic outflow.", "protein": "\u03b12-adrenoceptor", "relationship_type": "protective", "source_pmcid": "PMC7122603" }, { "confidence": "high", "disease": "Lassa fever", "glycan_involvement": "Requires host glycosylation of \u03b1-dystroglycan for binding", "mechanism": "Mediates viral entry into host cells via \u03b1-dystroglycan", "protein": "Lassa virus glycoprotein", "protein_enriched": { "function": "Seems to possess an anti-inflammatory activity as it can reverse the barrier-decreasing effects of TNF alpha. Might therefore contribute to the lack of inflammatory reaction seen during infection in s", "gene_name": "GP", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "Q66800" }, "relationship_type": "causal", "source_pmcid": "PMC7122670" }, { "confidence": "high", "disease": "Lassa fever", "glycan_involvement": "N- and O-glycosylation required for virus binding", "mechanism": "Acts as the major cell-surface receptor for Lassa virus glycoprotein", "protein": "\u03b1-dystroglycan", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (host factor)", "source_pmcid": "PMC7122670" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune recognition", "mechanism": "Mediates viral entry and immune evasion", "protein": "Ebola virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7122670" }, { "confidence": "medium", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation affects infectivity and immune evasion", "mechanism": "Mediates viral entry and pathogenesis", "protein": "Marburg virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7122670" }, { "confidence": "medium", "disease": "Molecular imaging of viral infection", "glycan_involvement": "Glycoprotein nature enables cell-surface expression and probe uptake", "mechanism": "Reporter gene for in vivo imaging of viral spread", "protein": "SLC5A5 (sodium/iodide symporter)", "protein_enriched": { "function": "Sodium:iodide symporter that mediates the transport of iodide into the thyroid gland (PubMed:12488351, PubMed:18372236, PubMed:18708479, PubMed:20797386, PubMed:31310151, PubMed:32084174, PubMed:88066", "gene_name": "SLC5A5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q92911" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122670" }, { "confidence": "medium", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation affects probe distribution and detection", "mechanism": "Radiolabeled albumin used to detect vessel leakage, a hallmark of EVD", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC7122670" }, { "confidence": "medium", "disease": "Neuroinflammation (e.g., Ebola virus disease)", "glycan_involvement": "Glycosylation may affect ligand binding and imaging sensitivity", "mechanism": "Imaging marker for activated macrophages in neuroinflammation", "protein": "TSPO (Translocator protein)", "relationship_type": "biomarker", "source_pmcid": "PMC7122670" }, { "confidence": "low", "disease": "Ebola virus disease (model system)", "glycan_involvement": "Glycosylation may modulate protein-protein interactions", "mechanism": "Binds to Ebola virus minigenome trailer region, promoting replication", "protein": "Heat-shock protein A8", "relationship_type": "host factor", "source_pmcid": "PMC7122670" }, { "confidence": "medium", "disease": "Asthma/COPD exacerbation", "glycan_involvement": "Glycosylation required for secretion and activity", "mechanism": "Identified as a biomarker for viral exacerbation in organ-on-chip models", "protein": "Macrophage colony-stimulating factor", "relationship_type": "biomarker", "source_pmcid": "PMC7122670" }, { "confidence": "high", "disease": "Influenza A infection", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion", "mechanism": "Mediates viral entry into host cells", "protein": "Influenza A virus hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7122670" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "VP7 is a glycoprotein; glycosylation is important for proper folding and antigenicity.", "mechanism": "VP7 is the outer capsid glycoprotein of rotavirus, elicits neutralizing antibodies and is essential for viral infectivity.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "causal", "source_pmcid": "PMC7122688" }, { "confidence": "high", "disease": "Norovirus infection", "glycan_involvement": "VP1 P domain binds to specific host glycans (HBGAs) for cell entry.", "mechanism": "VP1 forms the norovirus capsid and mediates binding to host cell HBGAs, enabling infection.", "protein": "VP1 (Norovirus capsid protein)", "relationship_type": "causal", "source_pmcid": "PMC7122688" }, { "confidence": "high", "disease": "Norovirus infection", "glycan_involvement": "Specific glycan structures (fucosylated, A/B/Lewis antigens) are required for viral binding.", "mechanism": "HBGAs on host cells serve as receptors for norovirus attachment and entry.", "protein": "Histo-blood group antigens (HBGAs)", "relationship_type": "causal/susceptibility factor", "source_pmcid": "PMC7122688" }, { "confidence": "high", "disease": "Resistance to Norwalk virus infection", "glycan_involvement": "FUT2-dependent fucosylation is required for HBGA synthesis on mucosal surfaces.", "mechanism": "Loss-of-function mutations in FUT2 prevent expression of HBGAs, conferring resistance to Norwalk virus.", "protein": "FUT2 (\u03b1(1,2) fucosyltransferase)", "relationship_type": "protective", "source_pmcid": "PMC7122688" }, { "confidence": "medium", "disease": "Norovirus infection", "glycan_involvement": "Lewis antigens are specific glycan structures recognized by norovirus capsid.", "mechanism": "Lewis antigen expression modulates susceptibility to different norovirus strains.", "protein": "Lewis antigens", "relationship_type": "susceptibility factor", "source_pmcid": "PMC7122688" }, { "confidence": "high", "disease": "Rotavirus diarrhea", "glycan_involvement": "VP4 is a glycoprotein; glycosylation affects function and antigenicity.", "mechanism": "VP4 is the spike protein mediating rotavirus attachment and entry; elicits neutralizing antibodies.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122688" }, { "confidence": "medium", "disease": "Rotavirus diarrhea", "glycan_involvement": "NSP4 is a glycoprotein; glycosylation may affect its function.", "mechanism": "NSP4 is a viral enterotoxin contributing to diarrhea pathogenesis.", "protein": "NSP4", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11194" }, "relationship_type": "causal", "source_pmcid": "PMC7122688" }, { "confidence": "medium", "disease": "Rotavirus diarrhea", "glycan_involvement": "VP6 is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "VP6 is the middle layer protein, used for group classification and diagnosis.", "protein": "VP6", "relationship_type": "causal/diagnostic", "source_pmcid": "PMC7122688" }, { "confidence": "medium", "disease": "Rotavirus diarrhea", "glycan_involvement": "VP2 is a glycoprotein; glycosylation may affect assembly.", "mechanism": "VP2 forms the inner core of rotavirus, essential for genome packaging.", "protein": "VP2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "structural/causal", "source_pmcid": "PMC7122688" }, { "confidence": "medium", "disease": "Sapovirus infection", "glycan_involvement": "Glycan structures on host cells mediate viral binding.", "mechanism": "Sapoviruses may also use HBGAs as attachment factors for infection.", "protein": "Histo-blood group antigens (HBGAs)", "relationship_type": "causal/susceptibility factor", "source_pmcid": "PMC7122688" }, { "confidence": "high", "disease": "Cardiac Infarction", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP activates complement pathways and is elevated in tissue alteration during cardiac infarction.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune components.", "mechanism": "CRP levels correlate with intestinal inflammation and disease activity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Glycosylation influences CRP's immune recognition.", "mechanism": "CRP is elevated in systemic inflammation and used to monitor disease activity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Glycosylation affects its solubility and aggregation.", "mechanism": "Serum amyloid A is increased during acute-phase response in IBD.", "protein": "Serum amyloid A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation modulates haptoglobin's binding to hemoglobin.", "mechanism": "Haptoglobin is elevated as an acute-phase reactant in SLE.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Leukocyte Adhesion Deficiency", "glycan_involvement": "Sialyl Lewis X glycan on leukocyte glycoproteins is essential for binding.", "mechanism": "Defective interaction between P-selectin and sialyl Lewis X-modified glycoproteins impairs leukocyte adhesion.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Leukocyte Adhesion Deficiency", "glycan_involvement": "Sialyl Lewis X glycan modification required for interaction.", "mechanism": "E-selectin binds glycoprotein ligands on leukocytes; deficiency disrupts rolling and adhesion.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC7122703" }, { "confidence": "medium", "disease": "Chronic Granulomatous Disease", "glycan_involvement": "Glycosylation regulates VCAM-1's adhesive properties.", "mechanism": "VCAM-1 expression is altered in chronic inflammation, affecting leukocyte migration.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "medium", "disease": "Chediak\u2013Higashi Syndrome", "glycan_involvement": "Glycosylation affects ligand binding and immune cell interaction.", "mechanism": "ICAM-1 mediates leukocyte adhesion; defects contribute to impaired immune response.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation influences CRP's stability and immune activation.", "mechanism": "CRP is markedly elevated in systemic inflammatory response syndrome and sepsis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7122703" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields the protein from immune recognition and affects infectivity.", "mechanism": "Mediates viral entry into host cells via receptor binding and membrane fusion.", "protein": "SARS coronavirus Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Acquired Immunodeficiency Syndrome (AIDS)", "glycan_involvement": "Dense N-glycan shield modulates immune evasion and receptor binding.", "mechanism": "Binds CD4 and coreceptors to mediate viral entry into T cells.", "protein": "HIV-1 Envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation modulates receptor binding and antigenicity.", "mechanism": "Binds sialic acid on host cells to initiate infection.", "protein": "Influenza Hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Heavily glycosylated mucin-like domain shields from immune detection.", "mechanism": "Mediates viral attachment and entry into host cells.", "protein": "Ebolavirus Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation affects antibody accessibility and vaccine design.", "mechanism": "Target for neutralizing antibodies and vaccine development.", "protein": "SARS coronavirus Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Acquired Immunodeficiency Syndrome (AIDS)", "glycan_involvement": "Glycan shield is a major obstacle for antibody binding.", "mechanism": "Target for broadly neutralizing antibodies.", "protein": "HIV-1 Envelope glycoprotein gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation sites influence antigenic drift and immune escape.", "mechanism": "Target for neutralizing antibodies and vaccines.", "protein": "Influenza Hemagglutinin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7122892" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Presence in patient samples indicates infection.", "protein": "SARS coronavirus Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7122892" }, { "confidence": "medium", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation impacts immunoassay detection.", "mechanism": "Detected in blood of infected individuals.", "protein": "Ebolavirus Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7122892" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation may modulate transmissibility and immune evasion.", "mechanism": "Superspreading events linked to high viral load and efficient transmission, possibly influenced by glycoprotein properties.", "protein": "SARS coronavirus Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7122892" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and immune recognition.", "mechanism": "MOG is a target of autoimmune T and B cell responses; molecular mimicry with viral antigens may trigger autoimmunity.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal/autoantigen", "source_pmcid": "PMC7122906" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation status may modulate immunogenicity.", "mechanism": "MBP-specific T cells are increased in MS; molecular mimicry with viral peptides may drive autoimmunity.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "causal/autoantigen", "source_pmcid": "PMC7122906" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "PLP is a target of autoreactive T cells; viral mimicry may contribute to epitope spreading.", "protein": "Proteolipid Protein (PLP)", "protein_enriched": { "function": "This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin", "gene_name": "PLP1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60201" }, "relationship_type": "causal/autoantigen", "source_pmcid": "PMC7122906" }, { "confidence": "high", "disease": "Progressive Multifocal Leukoencephalopathy (PML)", "glycan_involvement": "VP1 glycosylation mediates cell entry and tropism.", "mechanism": "JC virus infects oligodendrocytes via VP1, causing demyelination in immunosuppressed individuals.", "protein": "JC Virus VP1", "protein_enriched": { "function": "Forms an icosahedral capsid with a T=7 symmetry and a 40 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts ", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03089" }, "relationship_type": "causal", "source_pmcid": "PMC7122906" }, { "confidence": "high", "disease": "HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)", "glycan_involvement": "Glycosylation affects immune recognition and viral persistence.", "mechanism": "HTLV-I glycoprotein triggers immune-mediated CNS demyelination.", "protein": "HTLV-I Envelope Glycoprotein", "protein_enriched": { "function": "Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin l", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03356" }, "relationship_type": "causal", "source_pmcid": "PMC7122906" }, { "confidence": "medium", "disease": "Subacute Sclerosing Panencephalitis (SSPE)", "glycan_involvement": "Glycosylation modulates immune evasion and persistence.", "mechanism": "Measles virus persists in CNS; hemagglutinin is a major antigen in SSPE.", "protein": "Measles Virus Hemagglutinin", "protein_enriched": { "function": "Attaches the virus to the human SLAMF1/CD150 receptor for entry into host dendritic cells, macrophages, activated memory T cells and naive or memory B cells, thereby explaining the long immunosuppress", "gene_name": "H", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P08362" }, "relationship_type": "causal", "source_pmcid": "PMC7122906" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation may affect cross-reactivity.", "mechanism": "HSV glycoprotein D shares motifs with myelin proteins, possibly triggering autoimmunity.", "protein": "Herpes Simplex Virus Glycoprotein D", "relationship_type": "potential trigger (molecular mimicry)", "source_pmcid": "PMC7122906" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "N-glycosylation regulates ICAM-1 function and immune cell binding.", "mechanism": "ICAM-1 is upregulated in MS, facilitating leukocyte migration into CNS.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC7122906" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "VCAM-1 is elevated in MS CSF, mediating immune cell infiltration.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker/therapeutic target", "source_pmcid": "PMC7122906" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation is essential for ligand binding.", "mechanism": "E-selectin is increased in MS, promoting leukocyte-endothelial interactions.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC7122906" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Altered IgG glycosylation modulates immune complex clearance and inflammation.", "mechanism": "Autoantibodies (IgG) form immune complexes, driving disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation required for C3 stability and function.", "mechanism": "Low C3 due to consumption by immune complexes.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus", "glycan_involvement": "Glycosylation essential for C4 secretion and activity.", "mechanism": "Low C4 due to complement activation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is N-glycosylated, affecting its plasma half-life and function.", "mechanism": "CRP rises in response to inflammation and infection.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123040" }, { "confidence": "medium", "disease": "Bacterial Meningitis", "glycan_involvement": "Glycosylation affects transferrin isoforms and detection.", "mechanism": "CSF/serum transferrin ratio used in diagnosis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123040" }, { "confidence": "medium", "disease": "Febrile Neutropenia", "glycan_involvement": "N-glycosylation required for stability and activity.", "mechanism": "Used to stimulate erythropoiesis in cytopenic patients.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "Malaria", "glycan_involvement": "Sialic acid-containing O-glycans are critical for parasite binding.", "mechanism": "Plasmodium falciparum binds to glycophorin A on erythrocytes for invasion.", "protein": "Glycophorin A", "relationship_type": "causal", "source_pmcid": "PMC7123040" }, { "confidence": "medium", "disease": "Urinary Tract Infection", "glycan_involvement": "O-glycosylation of MUC1 forms a protective barrier.", "mechanism": "MUC1 on urothelium inhibits bacterial adhesion.", "protein": "Mucin-1 (MUC1)", "relationship_type": "protective", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "HIV Infection", "glycan_involvement": "N-glycosylation of CD4 modulates HIV binding affinity.", "mechanism": "HIV binds to CD4 on T cells for entry.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7123040" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "O-glycans mediate parasite recognition.", "mechanism": "Alternative erythrocyte receptor for Plasmodium invasion.", "protein": "Glycophorin B", "relationship_type": "causal", "source_pmcid": "PMC7123040" }, { "confidence": "high", "disease": "Pancreatic Ductal Adenocarcinoma", "glycan_involvement": "Glycosylation of ADAM17 regulates its trafficking and activity.", "mechanism": "ADAM17 mediates ectodomain shedding of growth factor receptors, promoting tumor progression.", "protein": "ADAM17 (A Disintegrin and Metalloproteinase 17)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123059" }, { "confidence": "high", "disease": "Inflammatory Diseases", "glycan_involvement": "N-glycosylation modulates ADAM17 substrate specificity.", "mechanism": "ADAM17 cleaves pro-TNF-alpha, releasing active TNF-alpha and driving inflammation.", "protein": "ADAM17 (A Disintegrin and Metalloproteinase 17)", "relationship_type": "causal", "source_pmcid": "PMC7123059" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "Receptor glycosylation affects susceptibility to ADAM17 cleavage.", "mechanism": "ADAM17-mediated shedding of the receptor alters growth signaling in tumors.", "protein": "Growth Hormone Receptor", "relationship_type": "biomarker", "source_pmcid": "PMC7123059" }, { "confidence": "medium", "disease": "Cancer (general)", "glycan_involvement": "EGFR glycosylation influences ligand binding and ADAM17-mediated activation.", "mechanism": "ADAM17 sheds EGFR ligands, activating EGFR signaling and promoting cancer cell proliferation.", "protein": "EGFR (Epidermal Growth Factor Receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123059" }, { "confidence": "medium", "disease": "Inflammatory Diseases", "glycan_involvement": "Glycosylation of TNF-alpha affects its stability and receptor interaction.", "mechanism": "Shedding by ADAM17 increases soluble TNF-alpha, exacerbating inflammation.", "protein": "TNF-alpha (Tumor Necrosis Factor alpha)", "relationship_type": "causal", "source_pmcid": "PMC7123059" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation is essential for thrombomodulin's anticoagulant function and cell surface localization.", "mechanism": "Acts as a cofactor for thrombin, activating protein C and inhibiting coagulation.", "protein": "Thrombomodulin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Heparan sulfate glycan chains are required for antithrombin binding and activity.", "mechanism": "Stimulate antithrombin activation, inhibiting thrombin and factor Xa.", "protein": "Heparan sulfate proteoglycans", "relationship_type": "protective", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation is critical for LDLR folding, stability, and function.", "mechanism": "Regulates LDL uptake; reduced LDLR leads to increased plasma LDL and atherosclerosis risk.", "protein": "LDL receptor (LDLR)", "relationship_type": "causal", "source_pmcid": "PMC7123129" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "O-glycosylation modulates ApoE receptor binding and lipid transport.", "mechanism": "Promotes cholesterol efflux and clearance of lipoproteins, reducing plaque formation.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "protective", "source_pmcid": "PMC7123129" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation affects ApoA1 stability and HDL function.", "mechanism": "Major HDL component, facilitates reverse cholesterol transport.", "protein": "Apolipoprotein A1 (ApoA1)", "relationship_type": "protective", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "N-glycosylation is required for integrin activation and ligand binding.", "mechanism": "Mediates platelet aggregation and thrombus formation.", "protein": "Integrin-\u03b12B\u03b23", "relationship_type": "causal", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "N-glycosylation is essential for VCAM1 cell surface expression and function.", "mechanism": "Promotes leukocyte adhesion to endothelium, initiating plaque formation.", "protein": "VCAM1", "relationship_type": "causal", "source_pmcid": "PMC7123129" }, { "confidence": "medium", "disease": "Vasculitis", "glycan_involvement": "Glycosylation modulates PECAM1-mediated cell adhesion.", "mechanism": "Involved in leukocyte transmigration during vascular inflammation.", "protein": "PECAM1", "relationship_type": "biomarker", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "Selectin binding requires specific sialylated and fucosylated glycans on ligands.", "mechanism": "Mediate leukocyte rolling and recruitment to inflamed endothelium.", "protein": "Selectins (e.g., E-selectin)", "relationship_type": "causal", "source_pmcid": "PMC7123129" }, { "confidence": "medium", "disease": "Vasculitis", "glycan_involvement": "N-glycosylation is necessary for endoglin stability and TGF-\u03b2 receptor interactions.", "mechanism": "Regulates endothelial cell function and angiogenesis in inflammation.", "protein": "Endoglin", "relationship_type": "biomarker", "source_pmcid": "PMC7123129" }, { "confidence": "high", "disease": "RSV pneumonia", "glycan_involvement": "Glycosylation of F protein is essential for proper folding and function.", "mechanism": "F protein mediates viral entry by promoting fusion of viral and host cell membranes.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "high", "disease": "hMPV pneumonia", "glycan_involvement": "Glycosylation required for fusion activity and immunogenicity.", "mechanism": "F protein mediates hMPV entry into host cells via membrane fusion.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "high", "disease": "RSV pneumonia", "glycan_involvement": "Glycosylation affects antibody binding and neutralization.", "mechanism": "Targeted by monoclonal antibodies (e.g., palivizumab) and fusion inhibitors.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123147" }, { "confidence": "medium", "disease": "RSV pneumonia", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune evasion.", "mechanism": "G protein mediates viral attachment to host cells; high sequence variability.", "protein": "Attachment glycoprotein (G protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "medium", "disease": "hMPV pneumonia", "glycan_involvement": "Glycosylation modulates host interaction and antigenicity.", "mechanism": "G protein mediates hMPV attachment to host cells.", "protein": "Attachment glycoprotein (G protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "medium", "disease": "Bronchiolitis obliterans", "glycan_involvement": "Glycosylation may affect persistence and immune response.", "mechanism": "RSV F protein-driven infection in lung transplant recipients associated with chronic airway injury.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "medium", "disease": "Acute allograft rejection", "glycan_involvement": "Glycosylation influences immunogenicity and host response.", "mechanism": "RSV/hMPV infection via F protein linked to increased acute rejection episodes post-lung transplant.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "low", "disease": "Chronic allograft dysfunction", "glycan_involvement": "Glycosylation patterns may modulate chronic immune activation.", "mechanism": "RSV G protein variability associated with chronic rejection in lung transplant recipients.", "protein": "Attachment glycoprotein (G protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "high", "disease": "Upper respiratory tract infection (URI)", "glycan_involvement": "Glycosylation required for infectivity.", "mechanism": "F protein mediates initial infection and spread in upper airway.", "protein": "Fusion glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "low", "disease": "RSV pneumonia", "glycan_involvement": "Glycosylation status affects function.", "mechanism": "SH protein may modulate host immune response and contribute to pathogenesis.", "protein": "Small hydrophobic glycoprotein (SH protein)", "relationship_type": "causal", "source_pmcid": "PMC7123147" }, { "confidence": "high", "disease": "Acute inflammation", "glycan_involvement": "Glycosylation affects CRP stability and function.", "mechanism": "CRP is upregulated as an acute-phase reactant in response to inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7123337" }, { "confidence": "high", "disease": "Acute inflammation", "glycan_involvement": "N-glycosylation modulates fibrinogen's solubility and clotting function.", "mechanism": "Fibrinogen increases during acute inflammation, contributing to exudate formation and tissue repair.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123337" }, { "confidence": "high", "disease": "Acute inflammation", "glycan_involvement": "Glycosylation influences haptoglobin's binding to hemoglobin.", "mechanism": "Haptoglobin is an acute-phase reactant elevated in inflammation.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123337" }, { "confidence": "medium", "disease": "Abdominal abscess", "glycan_involvement": "N-glycosylation affects transferrin's iron-binding and tissue distribution.", "mechanism": "Transferrin leaks into inflamed tissue, binds gallium-67 for imaging.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", 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"therapeutic_target", "source_pmcid": "PMC7123337" }, { "confidence": "medium", "disease": "Acute inflammation", "glycan_involvement": "Glycosylation impacts IgM structure and immune activation.", "mechanism": "Monoclonal IgM used for imaging inflammation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. 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"G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123337" }, { "confidence": "high", "disease": "Acute inflammation", "glycan_involvement": "Glycosylation is essential for antigenicity and antibody recognition.", "mechanism": "Surface glycoprotein on granulocytes targeted by labeled antibodies for infection imaging.", "protein": "NCA-90 (CD66b)", "relationship_type": "biomarker", "source_pmcid": "PMC7123337" }, { "confidence": "high", "disease": "Acute inflammation", "glycan_involvement": "Glycosylation is essential for antigenicity and antibody recognition.", "mechanism": "Surface glycoprotein on granulocytes targeted by labeled antibodies for infection imaging.", "protein": "NCA-95 (CD66c)", "relationship_type": "biomarker", "source_pmcid": "PMC7123337" }, { "confidence": "medium", "disease": "Abdominal abscess", "glycan_involvement": "Glycosaminoglycan structure critical for anti-adhesive and anti-inflammatory effects.", "mechanism": "Hyaluronan-based agents reduce adhesion and abscess formation post-surgery by modulating inflammation and enhancing fibrinolysis.", "protein": "Hyaluronan", "relationship_type": "protective", "source_pmcid": "PMC7123337" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Mediates viral fusion and entry into host cells.", "protein": "Respiratory Syncytial Virus F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "O-glycosylation modulates immune evasion.", "mechanism": "Facilitates viral attachment to host cell surface.", "protein": "Respiratory Syncytial Virus G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Extensive N-glycosylation shields epitopes from immune recognition.", "mechanism": "Binds ACE2 receptor to mediate viral entry.", "protein": "SARS-CoV Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects receptor binding and antigenicity.", "mechanism": "Binds sialic acid on host cells to initiate infection.", "protein": "Influenza Virus Hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates enzymatic activity.", "mechanism": "Cleaves sialic acid to facilitate viral release.", "protein": "Influenza Virus Neuraminidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123402" }, { "confidence": "medium", "disease": "Kidney Stone Disease", "glycan_involvement": "N-glycosylation essential for anti-aggregation function.", "mechanism": "Inhibits crystal aggregation in urine.", "protein": "Uromodulin", "relationship_type": "protective", "source_pmcid": "PMC7123402" }, { "confidence": "medium", "disease": "Urinary Tract Infection", "glycan_involvement": "O-glycosylation creates dense glycan shield.", "mechanism": "Forms mucosal barrier against pathogens.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7123402" }, { "confidence": "medium", "disease": "Immune Dysfunction", "glycan_involvement": "N-glycosylation modulates receptor interactions.", "mechanism": "Cell surface glycoprotein involved in immune cell signaling.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects spike binding affinity.", "mechanism": "Receptor for SARS-CoV-2 spike glycoprotein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Viral Entry", "glycan_involvement": "Glycosylation patterns influence tropism and immune evasion.", "mechanism": "Mediates attachment and fusion with host cells.", "protein": "Viral Envelope Glycoprotein (general)", "relationship_type": "causal", "source_pmcid": "PMC7123402" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects stability, half-life, and immunogenicity.", "mechanism": "Modulates immune response, increases anti-inflammatory mediators, reduces proinflammatory cytokines.", "protein": "Interferon beta-1a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Anemia (chronic kidney disease, chemotherapy-induced)", "glycan_involvement": "N-glycosylation essential for in vivo activity and serum half-life.", "mechanism": "Stimulates erythroid progenitor cell proliferation and differentiation.", "protein": "Epoetin alfa (erythropoietin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Anemia (chronic kidney disease, chemotherapy-induced)", "glycan_involvement": "Additional N-glycosylation sites increase serum half-life and reduce dosing frequency.", "mechanism": "Same as epoetin alfa but with increased glycosylation for longer half-life.", "protein": "Darbepoetin alfa", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Spinal fusion/degenerative disc disease", "glycan_involvement": "Glycosylation required for proper folding, secretion, and activity.", "mechanism": "Induces osteogenic gene transcription, promoting bone formation.", "protein": "Bone morphogenetic protein 2 (BMP-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Spinal fusion/tibial nonunions", "glycan_involvement": "Glycosylation affects stability and bioactivity.", "mechanism": "Promotes osteogenesis and bone repair.", "protein": "Bone morphogenetic protein 7 (BMP-7)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Neutropenia (chemotherapy-induced)", "glycan_involvement": "Recombinant form is nonglycosylated; natural G-CSF is glycosylated, which affects half-life.", "mechanism": "Stimulates neutrophil production and function.", "protein": "Filgrastim (G-CSF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Neutropenia (chemotherapy-induced), myeloid recovery", "glycan_involvement": "Glycosylation modulates receptor binding and serum half-life.", "mechanism": "Stimulates proliferation and differentiation of granulocyte and macrophage progenitors.", "protein": "Sargramostim (GM-CSF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Chronic hepatitis B and C", "glycan_involvement": "Glycosylation impacts stability and immunogenicity.", "mechanism": "Antiviral, immunomodulatory, and antiproliferative effects.", "protein": "Interferon alfa-2a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "medium", "disease": "Vitiligo", "glycan_involvement": "Recombinant form is nonglycosylated; glycosylation not critical for activity.", "mechanism": "Induces melanocyte apoptosis via CD8+ T cell activation.", "protein": "Interferon gamma-1b", "relationship_type": "causal", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Congenital/acquired generalized lipodystrophy", "glycan_involvement": "Analog is nonglycosylated; native leptin is not glycosylated.", "mechanism": "Restores leptin signaling, improving metabolic control.", "protein": "Metreleptin (leptin analog)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123448" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Altered glycosylation patterns modulate immunomodulatory function.", "mechanism": "Serum levels increase during acute phase response.", "protein": "Alpha-1-acid glycoprotein (Orosomucoid)", "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency", "glycan_involvement": "Glycosylation affects stability and serum half-life.", "mechanism": "Deficiency leads to unregulated protease activity and tissue damage.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation influences hemoglobin binding and clearance.", "mechanism": "Levels rise in acute phase response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Altered N-glycosylation (loss of sialic acid) is diagnostic.", "mechanism": "Carbohydrate-deficient transferrin is a marker for chronic liver disease and alcohol abuse.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Low levels indicate impaired copper transport.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Fucosylated forms are more specific for malignancy.", "mechanism": "Elevated in hepatocellular carcinoma and germ cell tumors.", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Aberrant glycosylation increases tumor specificity.", "mechanism": "Elevated in serum of patients with colorectal and other cancers.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Heavily O-glycosylated; glycan epitopes recognized by diagnostic antibodies.", "mechanism": "Serum levels elevated in ovarian cancer.", "protein": "CA 125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Sialylated glycan structure on glycoproteins and glycolipids.", "mechanism": "Elevated in pancreatic and gastrointestinal cancers.", "protein": "CA 19-9 (Sialyl-Lewis^a antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation patterns improve diagnostic specificity.", "mechanism": "Serum PSA elevated in prostate cancer.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC7123472" }, { "confidence": "high", "disease": "X-linked agammaglobulinemia", "glycan_involvement": "Glycosylation required for Ig stability and function", "mechanism": "Deficiency or absence of immunoglobulins due to B cell defect", "protein": "Immunoglobulins (Ig)", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Common variable immunodeficiency (CVID)", "glycan_involvement": "Glycosylation affects Ig secretion and half-life", "mechanism": "Low levels of immunoglobulins impair immune response", "protein": "Immunoglobulins (Ig)", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Selective IgA deficiency", "glycan_involvement": "Glycosylation critical for IgA transport and function", "mechanism": "Absent or low IgA leads to mucosal immune defects", "protein": "Immunoglobulins (IgA)", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "medium", "disease": "LAD-syndrome I", "glycan_involvement": "N-glycosylation required for ICAM-1 function", "mechanism": "Defective adhesion molecule impairs leukocyte migration", "protein": "ICAM-1 (CD54)", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Mannose binding protein deficiency", "glycan_involvement": "MBP binds mannose glycans on pathogens", "mechanism": "Deficiency impairs lectin pathway of complement activation", "protein": "Mannose Binding Protein (MBP)", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "medium", "disease": "C1-inhibitor deficiency", "glycan_involvement": "Glycosylation affects C1-inhibitor stability", "mechanism": "Deficiency leads to uncontrolled complement activation", "protein": "C1-inhibitor", "relationship_type": "causal", "source_pmcid": "PMC7123502" }, { "confidence": "medium", "disease": "Immune-mediated necrotising myopathy", "glycan_involvement": "Glycosylation may affect antigenicity", "mechanism": "Autoantibodies against HMG CoA Reductase found in patients", "protein": "HMG CoA Reductase", "relationship_type": "biomarker", "source_pmcid": "PMC7123502" }, { "confidence": "medium", "disease": "Selective IgA deficiency", "glycan_involvement": "SC is a glycopeptide, glycosylation required for transport", "mechanism": "SC binds to IgM in IgA deficiency to maintain mucosal immunity", "protein": "Secretory Component (SC)", "relationship_type": "compensatory", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Idiopathic thrombocytopenic purpura", "glycan_involvement": "Glycosylation influences Fc-mediated immunomodulation", "mechanism": "IVIG used to treat autoimmune platelet destruction", "protein": "Immunoglobulins (Ig)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Kawasaki\u2019s disease", "glycan_involvement": "Glycosylation modulates anti-inflammatory activity", "mechanism": "IVIG therapy reduces inflammation and coronary risk", "protein": "Immunoglobulins (Ig)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123502" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to host cell receptors.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "N-glycosylation affects antigenicity and immune evasion.", "mechanism": "Determines host range and tissue tropism in avian species.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "high", "disease": "Feline Infectious Peritonitis", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Facilitates viral entry into feline cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "high", "disease": "Mouse Hepatitis", "glycan_involvement": "Glycosylation influences host specificity.", "mechanism": "Mediates attachment and fusion with murine cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation may affect virion stability.", "mechanism": "Essential for virus assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "medium", "disease": "Mouse Hepatitis", "glycan_involvement": "Recognizes and binds host glycans.", "mechanism": "Facilitates attachment to sialic acid-containing receptors.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "causal", "source_pmcid": "PMC7123520" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation impacts antibody accessibility.", "mechanism": "Target for neutralizing antibodies and vaccine design.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123520" }, { "confidence": "high", "disease": "Barrett's Esophagus", "glycan_involvement": "Aberrant O-glycosylation patterns in mucins affect epithelial protection.", "mechanism": "Altered mucin glycosylation contributes to metaplasia and progression to dysplasia.", "protein": "Mucin (MUC1, MUC2)", "relationship_type": "causal", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation affects stability and detection in stool assays.", "mechanism": "Elevated fecal calprotectin reflects neutrophil infiltration in gut mucosa.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "N-glycosylation modulates antimicrobial activity and immunogenicity.", "mechanism": "Fecal lactoferrin is increased in active IBD due to neutrophil degranulation.", "protein": "Lactoferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate", "gene_name": "LTF", "glycan_count": 254, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01521EA", "G02030ZB", "G02628JF", "G03644CB", "G04657PL", "G05962QB", "G06247RL", "G06356OH", "G07162IJ", "G08110WX", "G08146BT", "G08290VR", "G08918WF", "G10256JP", "G10846ZT", "G11041DA", "G11629QQ", "G12745LE", "G14994KB", "G15127JD", "G15169WU", "G17208MA", "G17689DH", "G20312EM", "G22310AV", "G23432EQ", "G23453IV", "G23863VK", "G25418HZ", "G25451PN", "G26377UA", "G27058EU", "G27516OE", "G27947YN", "G27993JQ", "G28622IK", "G29880MM", "G31544HA", "G31986NC", "G32332VU", "G32788FZ", "G33608TH", "G34617SM", "G34989PA", "G35253PZ", "G35541EV", "G37818NZ", "G37868ZX", "G39471UU", "G39619TI", "G40574BA", "G40834TG", "G42358LZ", "G42962KI", "G43223CG", "G44215PV", "G44444MB", "G45395BF", "G45495MK", "G46524LG", "G46687AB", "G47012YE", "G47518TP", "G47644PP", "G47950XN", "G48414YA", "G50856PC", "G51413EV", "G52890YB", "G55132BD", "G56749GV", "G57776ZS", "G57818FI", "G58667NI", "G58954YZ", "G59536GA", "G59626AS", "G60177UT", "G60834IK", "G61256FT", "G61937QU", "G62765YT", "G63381RX", "G64409MC", "G65092SV", "G65344XH", "G65540UB", "G66163OV", "G66766XF", "G67164EE", "G70101JE", "G70232NH", "G70619PT", "G70894RY", "G71146HJ", "G72398FA", "G72797UR", "G74264KM", "G75051CY", "G75418YA", "G75568BH", "G75983OB", "G76295SF", "G76613WN", "G77252PU", "G77459ND", "G77582RK", "G78059CC", "G79286RS", "G79666IR", "G80075MS", "G80223IX", "G80669SJ", "G80920RR", "G81198YO", "G81263BG", "G81375TC", "G81637OR", "G82443XX", "G82830MN", "G83229XP", "G83460ZZ", "G83555HU", "G84452RH", "G84467IZ", "G86226EA", "G86795LJ", "G86880BF", "G87051GH", "G87123QX", "G88374WZ", "G90348RI", "G90382BL", "G91255CS", "G91473PK", "G92135MA", "G92275SC", "G93284HQ", "G93656SY", "G93683YO", "G95977AE", "G96577RX", "G99679NM", "G27945LI", "G63628AV", "G02815KT", "G03127AL", "G03382KH", "G04854VP", "G05724UK", "G06110VR", "G07810QS", "G10773YW", "G10819WX", "G11870QZ", "G14669DU", "G14972EH", "G15664MX", "G20210JR", "G20425TQ", "G20706XG", "G22140GZ", "G22768VO", "G23294PN", "G24835MQ", "G25079LO", "G26330YA", "G26403SG", "G27126ED", "G27251WT", "G29299MO", "G29580WD", "G31916IQ", "G33416PL", "G33609NS", "G34105RF", "G37399XV", "G37412TK", "G37692EO", "G39188ZX", "G40926MX", "G41071NU", "G46691LC", "G46902YN", "G49874UX", "G50045TK", "G51640FO", "G51806IG", "G52527GH", "G54612UD", "G55220VL", "G55383ZG", "G59324HL", "G59924QI", "G60145BJ", "G62837OZ", "G63041LO", "G64394MX", "G64527OM", "G64751KD", "G65019XG", "G66621EA", "G66676MI", "G66760KM", "G68698AP", "G70822IO", "G72291OX", "G72667IM", "G72735IY", "G72747WU", "G74430RZ", "G74724QE", "G77547TA", "G79568CQ", "G80333GO", "G80966KZ", "G81295CK", "G82020ZR", "G82119TF", "G82463GQ", "G83646BJ", "G84820NF", "G84862VB", "G85228QD", "G86408JD", "G87661QW", "G89319AW", "G90093AU", "G90575OW", "G90659AW", "G91636VS", "G92406TI", "G93718GY", "G94854LT", "G95046LV", "G98611JV", "G99668VU", "G04909DG", "G12313PD", "G26421QW", "G07392QY", "G14047PA", "G26295XE", "G57449OF", "G68283NG", "G74587YW", "G75927AR", "G76478FT", "G89241QS", "G90544QC", "G90974PL", "G96921ZU" ], "uniprot_id": "P02788" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "medium", "disease": "Helicobacter pylori infection", "glycan_involvement": "Fc glycosylation influences antibody function and detection.", "mechanism": "Serology detects anti-H. pylori IgG as evidence of exposure.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "Crohn's Disease", "glycan_involvement": "Glycosylation of antibody affects antigen recognition.", "mechanism": "ASCA positivity helps differentiate Crohn's from ulcerative colitis.", "protein": "Anti-Saccharomyces cerevisiae antibody (ASCA)", "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "Ulcerative Colitis", "glycan_involvement": "Glycosylation of antibody modulates immune response.", "mechanism": "p-ANCA positivity is associated with ulcerative colitis.", "protein": "p-ANCA", "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "C. difficile Colitis", "glycan_involvement": "Toxin glycosylation affects cell binding and cytotoxicity.", "mechanism": "Toxins A/B disrupt mucosal barrier, causing pseudomembranous colitis.", "protein": "C. difficile Toxin A/B", "relationship_type": "causal", "source_pmcid": "PMC7123601" }, { "confidence": "medium", "disease": "Chronic Liver Disease", "glycan_involvement": "N-glycosylation changes reflect hepatic synthetic defects.", "mechanism": "Altered transferrin glycoforms (e.g., carbohydrate-deficient transferrin) indicate liver dysfunction.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "medium", "disease": "Chronic Liver Disease", "glycan_involvement": "Glycosylation status affects half-life and function.", "mechanism": "Hypoalbuminemia is a marker of liver synthetic failure.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123601" }, { "confidence": "medium", "disease": "Anemia of Chronic Disease", "glycan_involvement": "N-glycosylation required for stability and bioactivity.", "mechanism": "Recombinant erythropoietin used to treat anemia.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123601" }, { "confidence": "high", "disease": "HIV infection/AIDS", "glycan_involvement": "gp120 is heavily N-glycosylated; glycan shield is targeted by defensins.", "mechanism": "Defensins (HNP-1-3, HNP-4, RC-1/2) bind glycosylated gp120, blocking viral attachment and entry.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Gb2 is glycosylated; defensin binding may involve glycan moieties.", "mechanism": "Alpha-defensins (HNP1-3, HD5) and retrocyclin-2 bind viral glycoprotein Gb2, inhibiting viral entry.", "protein": "Gb2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Targets viral envelope glycoproteins (e.g., hemagglutinin, neuraminidase).", "mechanism": "LL-37 disrupts viral envelope and modulates host inflammatory response, reducing infection severity.", "protein": "LL-37", "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Targets viral envelope glycoproteins (e.g., F and G proteins).", "mechanism": "LL-37 directly inactivates virus and protects epithelial cells from infection and cell death.", "protein": "LL-37", "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Human papillomavirus infection/cervical cancer", "glycan_involvement": "L2 is a minor capsid protein with potential glycosylation; defensin binding may involve glycan residues.", "mechanism": "HD5 blocks HPV infection by interacting with viral particles and blocking L2 cleavage, preventing entry.", "protein": "HD5", "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "Protease itself is not glycosylated, but viral envelope glycoproteins are essential for entry.", "mechanism": "Protegrin-1 and RC-1 inhibit NS2B/NS3 serine protease, blocking viral replication.", "protein": "NS2B/NS3 protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Targets glycosylated viral envelope proteins.", "mechanism": "hBD3 inhibits HSV-2 infection by binding viral glycoproteins and blocking entry.", "protein": "hBD3", "protein_enriched": { "function": "", "gene_name": "DEFB103A", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q5U7J2" }, "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Atopic dermatitis with eczema vaccinatum", "glycan_involvement": "Targets viral envelope glycoproteins.", "mechanism": "Reduced LL-37 expression in AD predisposes to eczema vaccinatum after vaccinia virus exposure.", "protein": "LL-37", "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "medium", "disease": "JC polyomavirus infection", "glycan_involvement": "Capsid proteins may be glycosylated; defensin binding may involve glycan residues.", "mechanism": "HD5 binds and stabilizes viral capsid, preventing genome release and infection.", "protein": "HD5", "relationship_type": "protective", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "HIV infection/AIDS", "glycan_involvement": "CD4 is N-glycosylated; glycan moieties may mediate defensin binding.", "mechanism": "Defensins (HNP-1-3, HNP-4, RC-1/2) bind CD4, blocking HIV entry.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123656" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation affects peptide binding and T cell recognition.", "mechanism": "Presentation of Ebola viral peptides to CD8+ cytotoxic T cells for immune clearance.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation modulates antigen presentation efficiency.", "mechanism": "Presentation of Ebola viral peptides to CD4+ helper T cells, leading to B cell activation and antibody production.", "protein": "MHC-II", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation influences receptor-ligand interactions.", "mechanism": "CD4+ T cells recognize MHC-II/viral peptide complexes, activating humoral immunity.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation affects T cell activation and stability.", "mechanism": "CD8+ T cells recognize MHC-I/viral peptide complexes, mediating cytotoxicity.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Fc glycosylation modulates effector functions.", "mechanism": "Antibodies bind Ebola virus epitopes, neutralizing the virus.", "protein": "Immunoglobulin (Antibody)", "relationship_type": "protective", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation shields epitopes from immune recognition.", "mechanism": "Viral glycoprotein mediates host cell entry and is a key vaccine antigen.", "protein": "Ebola Virus Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Dengue Fever", "glycan_involvement": "Glycosylation impacts antigenicity and immune evasion.", "mechanism": "Envelope glycoprotein enables viral entry and is targeted by neutralizing antibodies.", "protein": "Dengue Virus Envelope Glycoprotein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "Q6YMS4" }, "relationship_type": "causal", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects immunogenicity.", "mechanism": "Surface antigen is used in subunit vaccines to elicit protective immunity.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Human Papillomavirus Infection", "glycan_involvement": "Glycosylation influences vaccine efficacy.", "mechanism": "L1 protein is the basis for HPV subunit vaccines.", "protein": "Human Papillomavirus L1 Protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123697" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates receptor function and autoimmunity.", "mechanism": "Aberrant BCR signaling contributes to autoantibody production.", "protein": "B Cell Receptor (BCR)", "relationship_type": "biomarker", "source_pmcid": "PMC7123697" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation at fourth residue; glycosylation affects antigenicity and solubility.", "mechanism": "Contains T cell epitopes; used for serological detection of SARS-CoV infection.", "protein": "SARS-CoV Membrane (M) glycoprotein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins", "gene_name": "M", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P59596" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation may enhance immune recognition.", "mechanism": "Potential vaccine antigen due to T cell epitopes and immunogenicity.", "protein": "SARS-CoV Membrane (M) glycoprotein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins", "gene_name": "M", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P59596" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "No direct glycosylation mentioned; plant expression preserves antigenicity.", "mechanism": "Triggers early, strong antibody response; used for serological diagnosis.", "protein": "SARS-CoV Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P59595" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "No direct glycosylation mentioned.", "mechanism": "Induces long-term cell-mediated immunity; candidate for vaccine development.", "protein": "SARS-CoV Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P59595" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Human Papillomavirus (HPV) infection", "glycan_involvement": "Potential glycosylation in mammalian cells; plant-derived sequences may affect processing.", "mechanism": "DNA vaccine encoding L2 induces neutralizing antibodies; plant signal sequence enhances immunogenicity.", "protein": "HPV16 L2 protein", "protein_enriched": { "function": "May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03154" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Human Papillomavirus (HPV) infection", "glycan_involvement": "No direct glycosylation mentioned; plant signal sequence affects protein sorting.", "mechanism": "DNA vaccine encoding E7 induces adaptive cell-mediated immunity; plant signal sequence enhances secretion and immune response.", "protein": "HPV16 E7 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Plant glyco-engineering enables mammalian-like glycosylation for efficacy.", "mechanism": "Plant-produced human monoclonal antibodies used for Ebola therapy.", "protein": "ZMapp monoclonal antibodies", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "high", "disease": "Bioterrorism-related infections", "glycan_involvement": "Glyco-engineering allows mammalian-like glycosylation, improving efficacy and safety.", "mechanism": "Plant molecular farming enables rapid production of diagnostic antigens and therapeutics for biothreat agents.", "protein": "Plant-derived recombinant proteins (general)", "relationship_type": "diagnostic/therapeutic", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Marburg Virus Disease", "glycan_involvement": "Plant glyco-engineering enables functional glycosylation.", "mechanism": "Potential for rapid production of therapeutic antibodies against Marburg virus.", "protein": "Plant-derived monoclonal antibodies", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123727" }, { "confidence": "medium", "disease": "Human Papillomavirus (HPV) infection", "glycan_involvement": "May affect antigen processing and presentation.", "mechanism": "Plant signal sequences fused to antigens enhance humoral and cellular immune responses in DNA vaccines.", "protein": "Plant-derived immune-modulating sequences", "relationship_type": "protective", "source_pmcid": "PMC7123727" }, { "confidence": "high", "disease": "Dengue Fever (DF)", "glycan_involvement": "NS1 is glycosylated, which is essential for secretion and immunogenicity.", "mechanism": "Secreted NS1 is detectable in serum during acute infection and used for early diagnosis.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Glycosylation of NS1 modulates immune recognition and complement activation.", "mechanism": "NS1 and anti-NS1 antibodies trigger complement activation and inflammatory cytokines, contributing to vascular leakage.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Dengue Fever (DF)", "glycan_involvement": "N-glycosylation of E protein is critical for viral infectivity.", "mechanism": "E protein mediates viral entry into host cells; glycosylation affects infectivity and immune evasion.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Glycosylation of Fc\u03b3 receptor affects antibody binding and ADE efficiency.", "mechanism": "Fc\u03b3 receptor mediates antibody-dependent enhancement (ADE), increasing viral uptake and severity.", "protein": "Fc\u03b3 receptor", "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "medium", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Glycosylation is required for complement function and activation.", "mechanism": "Activated complement (C3a) contributes to inflammation and vascular leakage.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "medium", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Glycosylation is essential for complement activation.", "mechanism": "C5a promotes inflammatory responses and vascular permeability.", "protein": "Complement C5", "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Dengue Hemorrhagic Fever (DHF)", "glycan_involvement": "Fc glycosylation modulates interaction with Fc\u03b3 receptor and ADE.", "mechanism": "Pre-existing IgG antibodies mediate ADE, increasing risk of severe disease.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Dengue Fever (DF)", "glycan_involvement": "Glycosylation affects IgM stability and detection.", "mechanism": "IgM is produced in acute phase and used for serological diagnosis.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123783" }, { "confidence": "medium", "disease": "Plasma Leakage", "glycan_involvement": "Albumin glycosylation affects its pharmacokinetics and efficacy.", "mechanism": "Albumin is used as a plasma expander to treat shock due to plasma leakage.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123783" }, { "confidence": "medium", "disease": "Severe Bleeding", "glycan_involvement": "Contains multiple glycoproteins essential for coagulation.", "mechanism": "Used to correct coagulopathy and severe bleeding in dengue patients.", "protein": "Fresh Frozen Plasma", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123783" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation required for secretion and stability of sCD25.", "mechanism": "Elevated sCD25 reflects T-cell activation and is used as a diagnostic and disease activity marker in HLH.", "protein": "Soluble IL-2 receptor alpha (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Heavily glycosylated; glycosylation critical for lysosomal targeting and function.", "mechanism": "CD107a upregulation on NK/cytotoxic T cells is used to assess degranulation defects in HLH diagnosis.", "protein": "CD107a (LAMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation required for shedding and function.", "mechanism": "Soluble CD163 is a marker of macrophage activation, elevated in HLH.", "protein": "CD163", "protein_enriched": { "function": "Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. ", "gene_name": "CD163", "glycan_count": 74, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G27058EU", "G35541EV", "G52527GH", "G57776ZS", "G59536GA", "G62765YT", "G70441OD", "G79666IR", "G80479JV", "G80920RR", "G83460ZZ", "G87123QX", "G90659AW", "G93718GY", "G00912UN", "G06247RL", "G06356OH", "G08918WF", "G10019LZ", "G10486CT", "G10819WX", "G27947YN", "G28622IK", "G31852PQ", "G38663NM", "G40926MX", "G44753VC", "G48414YA", "G57888GL", "G59626AS", "G60033FS", "G62461SM", "G70619PT", "G72747WU", "G86880BF", "G99668VU", "G01485JJ", "G05962QB", "G08290VR", "G09831WQ", "G11629QQ", "G32788FZ", "G33791AF", "G41247ZX", "G41882MT", "G43223CG", "G45395BF", "G61256FT", "G76295SF", "G64527OM", "G15169WU", "G49642SA", "G80075MS", "G70232NH", "G04657PL", "G15664MX", "G27126ED", "G37692EO", "G46691LC", "G75568BH", "G84452RH", "G85282JO", "G89045VA", "G29068FM", "G43417UB", "G10488MI", "G20706XG", "G23505EP", "G26330YA", "G36442WJ", "G37509XX", "G77669RF", "G78787DI", "G92551JA" ], "uniprot_id": "Q86VB7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "X-linked lymphoproliferative disease (XLP)", "glycan_involvement": "Glycosylation may affect stability and cellular localization.", "mechanism": "XIAP deficiency causes XLP2, predisposing to HLH via impaired apoptosis regulation.", "protein": "XIAP", "protein_enriched": { "function": "Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as", "gene_name": "XIAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P98170" }, "relationship_type": "causal", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "X-linked lymphoproliferative disease (XLP)", "glycan_involvement": "Glycosylation may influence protein-protein interactions.", "mechanism": "SAP deficiency (XLP1) impairs immune cell signaling, leading to HLH after EBV infection.", "protein": "SAP (SLAM-associated protein)", "protein_enriched": { "function": "Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with S", "gene_name": "SH2D1A", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O60880" }, "relationship_type": "causal", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "EBV-associated HLH", "glycan_involvement": "Glycosylation of CD20 affects antibody binding and efficacy.", "mechanism": "Rituximab (anti-CD20) depletes B cells, used in EBV-HLH treatment.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123852" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation modulates receptor function and antibody recognition.", "mechanism": "Tocilizumab (anti-IL-6R) blocks IL-6 signaling, used in MAS therapy.", "protein": "IL-6 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "Chediak-Higashi syndrome", "glycan_involvement": "Glycosylation essential for lysosomal targeting.", "mechanism": "Defective CD107a upregulation reflects impaired degranulation in Chediak-Higashi, a cause of HLH.", "protein": "CD107a (LAMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "high", "disease": "Griscelli syndrome type 2", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Defective CD107a upregulation indicates impaired cytotoxic granule exocytosis in Griscelli syndrome type 2.", "protein": "CD107a (LAMP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "medium", "disease": "Macrophage activation syndrome (MAS)", "glycan_involvement": "Glycosylation required for secretion.", "mechanism": "Elevated sCD25 is used as a marker of T-cell activation in MAS.", "protein": "Soluble IL-2 receptor alpha (sCD25)", "relationship_type": "biomarker", "source_pmcid": "PMC7123852" }, { "confidence": "medium", "disease": "Pulmonary Arterial Hypertension", "glycan_involvement": "Glycosylation affects ACE2 stability and cell surface expression, influencing its activity in pulmonary tissues.", "mechanism": "ACE2 regulates pulmonary vascular tone and remodeling via angiotensin II metabolism.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7123895" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation of ACE2 modulates its interaction with the viral spike protein and susceptibility to infection.", "mechanism": "ACE2 acts as the cellular receptor for SARS coronavirus, mediating viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7123895" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection", "glycan_involvement": "Glycosylation of ACE2 is critical for spike protein binding and viral infectivity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV, facilitating viral attachment and internalization.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7123895" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Altered glycosylation patterns reflect inflammation", "mechanism": "Serum levels increase during acute phase response", "protein": "Alpha-1-acid glycoprotein (Orosomucoid)", "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Glycosylation affects stability and function", "mechanism": "Deficiency or abnormal glycoforms indicate liver dysfunction", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Hemolytic anemia", "glycan_involvement": "Glycosylation essential for hemoglobin binding", "mechanism": "Decreased levels indicate increased hemolysis", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Iron deficiency anemia", "glycan_involvement": "Carbohydrate-deficient transferrin is a marker for alcohol abuse", "mechanism": "Increased transferrin levels in iron deficiency", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "Glycosylation required for secretion and stability", "mechanism": "Low ceruloplasmin levels indicate copper metabolism disorder", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Reduced galactosylation/fucosylation linked to disease activity", "mechanism": "Altered Fc glycosylation modulates immune response", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Fucosylated glycoforms are more specific for cancer", "mechanism": "Elevated serum levels in liver cancer", "protein": "Alpha-fetoprotein", "protein_enriched": { "function": "Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties", "gene_name": "AFP", "glycan_count": 49, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G57321FI", "G00406II", "G48414YA", "G02030ZB", "G04791QM", "G06356OH", "G07392QY", "G07995VK", "G11041DA", "G14047PA", "G14127XU", "G14994KB", "G22310AV", "G23295TF", "G23863VK", "G25520XG", "G27919IH", "G30460NZ", "G31916IQ", "G36191CD", "G39213VZ", "G43694RQ", "G46687AB", "G49874UX", "G50045TK", "G50353PP", "G56749GV", "G58667NI", "G66937TJ", "G75850OP", "G78059CC", "G80858MF", "G81295CK", "G84452RH", "G84467IZ", "G89993FE", "G90725ZC", "G91023GB", "G91365ZQ", "G91473PK", "G91636VS", "G96921ZU", "G49108TO", "G20425TQ", "G29857RC", "G52934AK", "G72797UR", "G79568CQ", "G86357DX" ], "uniprot_id": "P02771" }, "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Heavily O-glycosylated; glycan epitopes recognized by diagnostic antibodies", "mechanism": "Serum CA 125 elevated in ovarian cancer", "protein": "CA 125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Aberrant glycosylation increases tumor specificity", "mechanism": "CEA levels elevated in colorectal and other cancers", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered glycosylation patterns improve diagnostic specificity", "mechanism": "Elevated PSA in prostate cancer", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC7123940" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Fibrinogen is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Downregulation in serum is associated with early and active fibrogenic processes.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Glycosylation status may influence fragment release and detection.", "mechanism": "Serum levels are downregulated in ALD and increase with alcohol abstinence.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Hepatitis C virus (HCV) infection", "glycan_involvement": "Glycosylation may affect fragment stability in circulation.", "mechanism": "Downregulation in serum precedes histological evidence of fibrosis in HCV patients.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation may modulate fragment release.", "mechanism": "Absence of fragment in serum is associated with active fibrogenesis in NASH.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Hepatitis B virus (HBV) infection", "glycan_involvement": "Glycosylation may affect fragment detection.", "mechanism": "Fragment absence in serum correlates with active fibrogenic process in HBV.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Autoimmune hepatitis (AH)", "glycan_involvement": "Glycosylation may influence fragment stability.", "mechanism": "Fragment absence in serum is linked to active fibrogenesis in AH.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Cryptogenic liver damage", "glycan_involvement": "Glycosylation may affect fragment release.", "mechanism": "Fragment absence in serum is associated with fibrogenesis of unknown etiology.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Altered glycosylation may contribute to dysfibrinogenemia.", "mechanism": "Dysfibrinogenemia and reduced fibrinogen levels observed in acute liver failure.", "protein": "Fibrinogen \u03b1-Chain", "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "medium", "disease": "Cancer (breast, ovarian, prostate, non-small cell lung, colorectal, pancreatic)", "glycan_involvement": "Glycosylation may affect fragment detection in cancer.", "mechanism": "Altered serum levels (diminished or increased) observed in various cancers.", "protein": "Fibrinogen \u03b1 C-chain 5.9 kDa fragment", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "Alcoholic liver disease (ALD)", "glycan_involvement": "Deficiency in glycosylation is the basis of CDT as a biomarker.", "mechanism": "Altered glycosylation (carbohydrate-deficiency) is used as a marker for chronic alcohol intake.", "protein": "Carbohydrate-deficient transferrin (CDT)", "relationship_type": "biomarker", "source_pmcid": "PMC7123997" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation of gp120 provides binding sites for nanoparticles.", "mechanism": "Silver nanoparticles bind gp120 glycoprotein knobs, inhibiting HIV-1 attachment to host cells.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124020" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Glycosylation enables antibody recognition.", "mechanism": "F protein on RSV surface detected by antibody-conjugated QDs for rapid diagnosis.", "protein": "F protein", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ1" }, "relationship_type": "biomarker", "source_pmcid": "PMC7124020" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "Glycosylation is critical for antigenicity.", "mechanism": "G protein on RSV surface detected by QDs for early infection identification.", "protein": "G protein", "relationship_type": "biomarker", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "SWCNTs functionalized with CAR protein detect adenovirus via Knob-CAR interaction.", "protein": "CAR protein", "relationship_type": "biomarker", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "Adenovirus infection", "glycan_involvement": "Glycosylation affects receptor specificity.", "mechanism": "Knob protein domain used for biosensor detection of adenovirus.", "protein": "Knob protein (Ad12)", "relationship_type": "biomarker", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "E. coli infection", "glycan_involvement": "O-antigen is a glycan determinant for bacterial identification.", "mechanism": "QDs coated with zinc(ii)-dipicolylamine stain E. coli mutants lacking O-antigen for detection.", "protein": "O-antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7124020" }, { "confidence": "low", "disease": "Kidney stones", "glycan_involvement": "Glycosylation may influence mineralization.", "mechanism": "Nanobacteria-like particles react with serum albumin, implicated in stone formation.", "protein": "Serum albumin", "relationship_type": "causal", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "Anthrax", "glycan_involvement": "Surface glycans are targeted for antimicrobial action.", "mechanism": "Sugar-coated SWCNTs bind spore surface carbohydrates, causing aggregation and inhibiting infection.", "protein": "Anthrax spore surface carbohydrates", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "DermaVir Patch enhances Gag-specific T cell responses for HIV control.", "protein": "Gag protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124020" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may influence enzyme activity.", "mechanism": "Fullerene derivatives inhibit HIV protease, blocking viral replication.", "protein": "HIV protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124020" }, { "confidence": "high", "disease": "Heart Failure", "glycan_involvement": "N-glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "Regulates cardiac contractility via cAMP signaling.", "protein": "Beta-Adrenergic Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation affects receptor surface expression.", "mechanism": "Controls airway smooth muscle tone and inflammation.", "protein": "Adenosine Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "N-glycosylation required for proper receptor function.", "mechanism": "Mediates neutrophil chemotaxis and immune response.", "protein": "Formyl Peptide Receptor (FPR)", "relationship_type": "causal", "source_pmcid": "PMC7124097" }, { "confidence": "high", "disease": "Retinitis Pigmentosa", "glycan_involvement": "Glycosylation essential for folding and stability.", "mechanism": "Mutations disrupt photoreceptor signaling.", "protein": "Rhodopsin", "protein_enriched": { "function": "Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-", "gene_name": "RHO", "glycan_count": 23, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03597FX", "G06356OH", "G07483YN", "G08520NM", "G11637WL", "G16828VN", "G23294PN", "G23453IV", "G29880MM", "G33609NS", "G48414YA", "G53168IY", "G53276NK", "G60145BJ", "G61751GZ", "G72735IY", "G75896PD", "G81282CC", "G82119TF", "G82942ZJ", "G84820NF", "G92570PJ", "G94854LT" ], "uniprot_id": "P08100" }, "relationship_type": "causal", "source_pmcid": "PMC7124097" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "N-glycosylation influences receptor responsiveness.", "mechanism": "Regulates vascular tone and blood pressure.", "protein": "Angiotensin II Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Parkinson's Disease", "glycan_involvement": "Glycosylation affects receptor localization.", "mechanism": "Modulates motor control in basal ganglia.", "protein": "Dopamine Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Depression", "glycan_involvement": "Glycosylation impacts receptor signaling.", "mechanism": "Regulates mood and neurotransmission.", "protein": "Serotonin Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Chronic Pain", "glycan_involvement": "Glycosylation modulates ligand affinity.", "mechanism": "Mediates analgesic signaling.", "protein": "Opioid Receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124097" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Glycosylation required for ligand recognition.", "mechanism": "Directs leukocyte migration.", "protein": "Chemokine Receptor", "relationship_type": "causal", "source_pmcid": "PMC7124097" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycosylation patterns observed in tumors.", "mechanism": "Aberrant GPCR signaling promotes tumor growth.", "protein": "GPCRs (general)", "relationship_type": "biomarker", "source_pmcid": "PMC7124097" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates binding to ACE2 receptor, enabling viral entry and infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Target for vaccine development due to its role in host cell entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Diffuse Alveolar Damage (DAD)", "glycan_involvement": "Glycosylation influences fusion efficiency.", "mechanism": "Facilitates viral spread in lung tissue via cell-to-cell fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation impacts envelope thickness and stability.", "mechanism": "Contributes to viral envelope structure and assembly.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Potential glycosylation may affect virulence.", "mechanism": "Acts as a virulence factor, influencing disease severity.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Not specified.", "mechanism": "Involved in genome encapsidation and antagonism of interferon response.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Acute pneumonia", "glycan_involvement": "Glycosylation modulates tissue tropism.", "mechanism": "Enables infection of lower respiratory tract cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "low", "disease": "Fibrosis/Honeycomb lung", "glycan_involvement": "Glycosylation may affect chronicity of infection.", "mechanism": "Persistent infection and immune response lead to lung remodeling.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation affects antibody recognition.", "mechanism": "Anti-spike antibodies correlate with recovery.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7124098" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation modulates neutralizing epitope exposure.", "mechanism": "Neutralizing antibodies against S protein confer protection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7124098" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry into respiratory epithelial cells.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and antigenicity.", "mechanism": "Cleaves sialic acids to facilitate viral release.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124101" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Promotes fusion of viral and host membranes.", "protein": "Fusion (F) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "Heavily glycosylated; O-glycans modulate immune recognition.", "mechanism": "Mediates viral attachment to host cells.", "protein": "Attachment (G) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "high", "disease": "Coronavirus Infection", "glycan_involvement": "N-glycosylation shields epitopes from immune detection.", "mechanism": "Facilitates viral entry via ACE2 receptor binding.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "medium", "disease": "Bocavirus Infection", "glycan_involvement": "Glycosylation influences virion stability.", "mechanism": "Structural glycoprotein involved in viral assembly.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "medium", "disease": "Bocavirus Infection", "glycan_involvement": "Glycosylation affects receptor interaction.", "mechanism": "Mediates cell entry.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "medium", "disease": "Parainfluenza", "glycan_involvement": "N-glycosylation required for activity.", "mechanism": "Involved in viral fusion and entry.", "protein": "E1 glycoprotein", "protein_enriched": { "function": "Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8JUX6" }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "medium", "disease": "Parainfluenza", "glycan_involvement": "Glycosylation modulates host interaction.", "mechanism": "Assists in viral attachment.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). 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Tethers the RNA-directed RNA polymerase L to th", "gene_name": "P", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03421" }, "relationship_type": "causal", "source_pmcid": "PMC7124101" }, { "confidence": "high", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Altered Fc glycosylation modulates inflammatory activity.", "mechanism": "Autoantibodies (IgG) mediate tissue damage.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Familial Mediterranean fever", "glycan_involvement": "Glycosylation affects amyloid fibril formation.", "mechanism": "Serum amyloid A deposition leads to amyloidosis.", "protein": "Amyloid A", "relationship_type": "causal", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Dense N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates viral entry via CD4 binding.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7124126" }, { "confidence": "medium", "disease": "Granulomatosis with polyangiitis", "glycan_involvement": "Glycosylation modulates complement activity.", "mechanism": "Complement activation contributes to vasculitis.", "protein": "Complement component C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 98, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49955PK", "G69834CE", "G95678HJ", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G05049YU", "G05724UK", "G06110VR", "G10471FG", "G10486CT", "G11115RO", "G14260UH", "G14972EH", "G15664MX", "G17208MA", "G20312EM", "G23294PN", "G23453IV", "G23719VF", "G26330YA", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G32104JU", "G33609NS", "G34029GR", "G34730YF", "G36442WJ", "G37399XV", "G39188ZX", "G39446WN", "G41247ZX", "G41840AI", "G42124LM", "G46503DX", "G46691LC", "G48414YA", "G49018RC", "G50282JC", "G55220VL", "G57317CE", "G57776ZU", "G59626AS", "G60145BJ", "G61302NC", "G62765YT", "G63041LO", "G64527OM", "G65000LJ", "G65184UU", "G66538GV", "G66676MI", "G67324HN", "G68490OW", "G70101JE", "G70160EA", "G70441OD", "G70619PT", "G72735IY", "G72747WU", "G72787SB", "G72790NZ", "G73430PD", "G76295SF", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84349RE", "G87661QW", "G90575OW", "G90659AW", "G92050GC", "G92406TI", "G92551JA", "G94470IW", "G95177YH", "G96091TT", "G96430BV", "G99679NM", "G22768VO", "G30769VJ", "G31544HA", "G70375MX", "G72398FA", "G78790NZ", "G86234IN", "G90093AU", "G43417UB", "G40702WU", "G49108TO", "G68668TB", "G83161QT" ], "uniprot_id": "P01024" }, "relationship_type": "biomarker", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation state influences aggregation propensity.", "mechanism": "Misfolded amyloid A accumulates in tissues.", "protein": "Amyloid A", "relationship_type": "causal", "source_pmcid": "PMC7124126" }, { "confidence": "medium", "disease": "Spontaneous bacterial peritonitis", "glycan_involvement": "Altered glycosylation reflects acute phase response.", "mechanism": "Transferrin glycoforms change in infection/inflammation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation affects IgG effector function.", "mechanism": "Oligoclonal IgG bands in CSF indicate disease.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Myasthenia gravis", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Autoantibodies target glycosylated receptor.", "protein": "Acetylcholine receptor (glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC7124126" }, { "confidence": "medium", "disease": "Cardiac myxoma", "glycan_involvement": "O-glycosylation contributes to tumor matrix.", "mechanism": "Myxoma cells secrete mucinous glycoproteins.", "protein": "Mucin-1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Toxic shock syndrome", "glycan_involvement": "Glycosylation modulates toxin activity and immune evasion.", "mechanism": "Exotoxins trigger systemic inflammation.", "protein": "Staphylococcal exotoxins (glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC7124126" }, { "confidence": "high", "disease": "Prion diseases (BSE, CJD, scrapie)", "glycan_involvement": "Glycosylation affects PrP folding and aggregation propensity.", "mechanism": "Misfolding of PrP leads to infectious aggregates causing neurodegeneration.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC7124132" }, { "confidence": "high", "disease": "Familial amyloid polyneuropathy", "glycan_involvement": "Glycosylation may modulate aggregation and stability.", "mechanism": "Misfolded transthyretin forms amyloid fibrils, disrupting nerve/muscle function.", "protein": "Transthyretin", "relationship_type": "causal", "source_pmcid": "PMC7124132" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Heavy N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates viral entry by binding to CD4 and CCR5/CXCR4 receptors.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124132" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Glycosylation modulates receptor function and HIV binding.", "mechanism": "CCR5 acts as a co-receptor for HIV entry; antagonists block infection.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124132" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Indirect; protease processes glycoprotein precursors.", "mechanism": "Protease inhibitors block viral maturation.", "protein": "HIV protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124132" }, { "confidence": "high", "disease": "AIDS (HIV infection)", "glycan_involvement": "Indirect; RT acts on glycoprotein-encoded viral RNA.", "mechanism": "RT inhibitors block viral genome replication.", "protein": "HIV reverse transcriptase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7124132" }, { "confidence": "medium", "disease": "Cystic fibrosis", "glycan_involvement": "Glycosylation may affect folding and stability.", "mechanism": "Slow unfolding kinetics of \u03b1-spectrin domains protect membrane integrity.", "protein": "\u03b1-spectrin", "relationship_type": "protective", "source_pmcid": "PMC7124132" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycoprotein-like structure facilitates substrate interaction.", "mechanism": "Chaperonins assist folding and prevent aggregation of misfolded proteins.", "protein": "GroEL/GroES", "relationship_type": "protective", "source_pmcid": "PMC7124132" }, { "confidence": "medium", "disease": "Transcriptional disorders", "glycan_involvement": "Glycosylation may affect nuclear localization and DNA binding.", "mechanism": "Mutations in TBP or TATA-box impair transcription.", "protein": "TATA-box binding protein (TBP)", "protein_enriched": { "function": "The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or ", "gene_name": "TBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P20226" }, "relationship_type": "biomarker", "source_pmcid": "PMC7124132" }, { "confidence": "medium", "disease": "Kaposi's sarcoma", "glycan_involvement": "gp120 glycosylation modulates immune evasion.", "mechanism": "HIV infection increases risk of Kaposi's sarcoma via immune suppression.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7124132" }, { "confidence": "medium", "disease": "Pulmonary fibrosis", "glycan_involvement": "Glycoprotein G mediates viral entry and immune evasion via glycosylation.", "mechanism": "Herpesvirus infection (AHV-4, AHV-5) proposed as causative agent for pulmonary fibrosis in donkeys.", "protein": "Herpesvirus glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Herpesvirus encephalitis", "glycan_involvement": "Glycosylation affects neuroinvasion and immune response.", "mechanism": "Glycoprotein G nucleotide sequence similarity links ASH-3 to EHV-1 neurovirulence.", "protein": "Herpesvirus glycoprotein G", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Equine coronavirus-induced encephalopathy", "glycan_involvement": "Spike glycoprotein glycosylation modulates host cell tropism.", "mechanism": "Spike glycoprotein mediates viral entry, leading to neurologic signs via hyperammonemia.", "protein": "Equine coronavirus spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "low", "disease": "Equine multinodular pulmonary fibrosis", "glycan_involvement": "Glycosylation impacts immune recognition and pathogenesis.", "mechanism": "Species-specific viral glycoproteins linked to pulmonary disease in donkeys.", "protein": "Equine arteritis virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Conjunctivitis", "glycan_involvement": "Cell wall glycoproteins mediate host immune response.", "mechanism": "Fungal glycoproteins trigger dacryoadenitis and duct inflammation.", "protein": "Histoplasma capsulatum glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Conjunctivitis", "glycan_involvement": "Surface glycoproteins facilitate adhesion and immune evasion.", "mechanism": "Bacterial glycoproteins contribute to chronic conjunctivitis.", "protein": "Staphylococcus aureus surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "high", "disease": "Renal disease (acute/chronic)", "glycan_involvement": "N-glycosylation modulates cytokine stability and activity.", "mechanism": "Elevated IL-6 levels indicate inflammation in gentamicin-induced acute kidney disease.", "protein": "Interleukin-6", "relationship_type": "biomarker", "source_pmcid": "PMC7125788" }, { "confidence": "high", "disease": "Renal disease (acute/chronic)", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Increased IL-1\u03b2 reflects acute inflammatory response in nephrotoxicity.", "protein": "Interleukin-1\u03b2", "relationship_type": "biomarker", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Laminitis", "glycan_involvement": "Glycosylation influences serum stability and detection.", "mechanism": "Elevated CKmb levels indicate muscle damage in laminitis and cardiac toxicity.", "protein": "CKmb (Creatine kinase MB)", "relationship_type": "biomarker", "source_pmcid": "PMC7125788" }, { "confidence": "medium", "disease": "Dermatophilosis", "glycan_involvement": "Surface glycoproteins facilitate host colonization.", "mechanism": "Bacterial glycoproteins mediate skin infection and immune response.", "protein": "Dermatophilus congolensis surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7125788" }, { "confidence": "high", "disease": "Autoimmunity (vaccine-induced)", "glycan_involvement": "Complex glycan on ASOR mimicked by viral glycoprotein triggers autoantibody response.", "mechanism": "SARS-CoV vaccine produced in monkey cells induces antibodies that cross-react with ASOR glycan structures, leading to autoimmunity.", "protein": "ASOR (asialo-orosomucoid)", "relationship_type": "causal", "source_pmcid": "PMC7129122" }, { "confidence": "high", "disease": "Autoimmunity (vaccine-induced)", "glycan_involvement": "Viral glycosylation pattern mimics host glycoprotein, causing molecular mimicry.", "mechanism": "Viral glycoprotein expresses glycan structures mimicking human ASOR, inducing anti-ASOR autoantibodies.", "protein": "SARS-CoV spike glycoprotein (implied)", "relationship_type": "causal", "source_pmcid": "PMC7129122" }, { "confidence": "medium", "disease": "SARS (Severe Acute Respiratory Syndrome)", "glycan_involvement": "ASOR complex glycan is the target of cross-reactive antibodies.", "mechanism": "ASOR glycan recognized by antibodies elicited by SARS-CoV vaccine; used to probe autoimmunogenicity.", "protein": "ASOR (asialo-orosomucoid)", "relationship_type": "biomarker", "source_pmcid": "PMC7129122" }, { "confidence": "low", "disease": "Skin cancer (melanoma)", "glycan_involvement": "Not directly specified, but hsp70 may be glycosylated and involved in immune modulation.", "mechanism": "hsp70 used to attract T cells and enhance immune response against melanoma in cancer vaccine strategy.", "protein": "Heat shock protein 70 (hsp70)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7129122" }, { "confidence": "high", "disease": "Ovarian cancer", "glycan_involvement": "Aberrant O-glycosylation increases immunogenicity and detection.", "mechanism": "Elevated serum levels correlate with tumor burden.", "protein": "CA125 (MUC16)", "relationship_type": "biomarker", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Altered N-glycosylation affects cell adhesion and immune evasion.", "mechanism": "Overexpressed in tumor tissue and released into blood.", "protein": "CEA (Carcinoembryonic Antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Cancer-specific glycoforms improve diagnostic specificity.", "mechanism": "Serum PSA levels rise with tumor progression.", "protein": "PSA (Prostate-Specific Antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Fucosylated N-glycans distinguish malignant from benign disease.", "mechanism": "Elevated AFP in serum is diagnostic for liver cancer.", "protein": "AFP (Alpha-fetoprotein)", "relationship_type": "biomarker", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "N-glycosylation modulates receptor dimerization and antibody binding.", "mechanism": "Overexpression drives tumor growth; targeted by monoclonal antibodies.", "protein": "HER2/neu", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7129345" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "O-glycosylation regulates ligand binding and cell motility.", "mechanism": "CD44 variant isoforms promote cell migration and metastasis.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Inflammatory diseases", "glycan_involvement": "Recognizes sialylated glycan ligands on leukocytes.", "mechanism": "Mediates leukocyte adhesion to endothelium during inflammation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "causal", "source_pmcid": "PMC7129345" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation affects binding to integrins.", "mechanism": "Facilitates immune cell infiltration into CNS.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC7129345" }, { "confidence": "medium", "disease": "Iron deficiency anemia", "glycan_involvement": "N-glycosylation pattern changes in disease.", "mechanism": "Altered glycoforms indicate iron metabolism disorders.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Reduced galactosylation and sialylation increase pathogenicity.", "mechanism": "Aberrant glycosylation promotes inflammation.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7129345" }, { "confidence": "high", "disease": "Chronic wasting disease (CWD)", "glycan_involvement": "Glycosylation of PrP influences aggregation and neurotoxicity.", "mechanism": "PrP amyloid deposition in brain nuclei is a hallmark of CWD pathology.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC7129843" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation affects antigenicity and immune evasion.", "mechanism": "Hemagglutinin mediates viral entry and is used for genotyping outbreak strains.", "protein": "Hemagglutinin (Measles virus)", "relationship_type": "causal", "source_pmcid": "PMC7129843" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Major hydrophilic region (residues 100\u2013170) contains glycosylation sites; mutations impact antigenicity.", "mechanism": "HBsAg mutations in glycosylation regions affect infectivity and immune recognition.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "biomarker", "source_pmcid": "PMC7129843" }, { "confidence": "medium", "disease": "Bovine viral diarrhea (BVD)", "glycan_involvement": "Hypervariable region V1 in E2 is subject to glycan modification, influencing immune escape.", "mechanism": "E2 is the major target of neutralizing antibodies and determines viral tropism.", "protein": "E2 glycoprotein (BVD virus)", "relationship_type": "causal", "source_pmcid": "PMC7129843" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense N-glycosylation forms a 'glycan shield' that protects Env from immune recognition.", "mechanism": "Env mediates viral entry and is a target for neutralizing antibodies; recombination and glycan shield affect therapy.", "protein": "HIV-1 Env glycoprotein", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7129843" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation modulates antigenicity and immune response.", "mechanism": "VP7 serotype determines strain specificity and vaccine coverage.", "protein": "VP7 glycoprotein (Rotavirus)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7129843" }, { "confidence": "high", "disease": "Kaposi's sarcoma", "glycan_involvement": "Glycosylation affects tropism and immune evasion.", "mechanism": "HHV-8 glycoproteins mediate cell entry and are associated with tumorigenesis.", "protein": "HHV-8 envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7129843" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Envelope glycoprotein may interact with host immune system via glycan structures.", "mechanism": "MSRV detected in plasma and CSF of MS patients; may act as a trigger or marker.", "protein": "MSRV envelope glycoprotein", "relationship_type": "biomarker/causal (possible)", "source_pmcid": "PMC7129843" }, { "confidence": "medium", "disease": "Arthritis (B19-associated)", "glycan_involvement": "Capsid glycosylation may influence tissue tropism and immune response.", "mechanism": "B19 persists in synovial tissue, potentially triggering autoimmune arthritis.", "protein": "B19 capsid glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7129843" }, { "confidence": "low", "disease": "Liver disease (TTV-associated)", "glycan_involvement": "Glycoprotein expression used for antibody detection; glycosylation may affect immunogenicity.", "mechanism": "TTV DNA detected in bile, liver, and serum; role in liver disease under investigation.", "protein": "TTV glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7129843" }, { "confidence": "high", "disease": "Avian Goiter/Thyroid Hyperplasia", "glycan_involvement": "TSH glycosylation affects receptor binding and bioactivity.", "mechanism": "TSH stimulates thyroid cell proliferation in response to low thyroxine, leading to hyperplasia.", "protein": "Thyroid Stimulating Hormone (TSH)", "relationship_type": "causal", "source_pmcid": "PMC7147455" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Insulin glycosylation is critical for stability and receptor interaction.", "mechanism": "Insulin deficiency or resistance leads to hyperglycemia and glycosuria.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC7147455" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glucagon glycosylation may modulate secretion and activity.", "mechanism": "Elevated glucagon promotes gluconeogenesis and hyperglycemia.", "protein": "Glucagon", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "Gcg", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55095" }, "relationship_type": "causal", "source_pmcid": "PMC7147455" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "VLDL glycosylation influences lipid transport and plaque deposition.", "mechanism": "Elevated VLDL correlates with plaque formation in arteries.", "protein": "VLDL", "relationship_type": "biomarker", "source_pmcid": "PMC7147455" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL glycosylation affects receptor-mediated clearance and plaque formation.", "mechanism": "High LDL is associated with increased risk of atherosclerotic plaques.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC7147455" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "HDL glycosylation modulates anti-inflammatory and cholesterol efflux functions.", "mechanism": "Low HDL is linked to increased atherosclerosis risk; HDL removes cholesterol from plaques.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC7147455" }, { "confidence": "medium", "disease": "Sinusitis", "glycan_involvement": "O-glycosylation of mucins is essential for mucus viscosity and pathogen trapping.", "mechanism": "Altered mucin production or glycosylation impairs mucociliary clearance, predisposing to infection.", "protein": "Mucins", "relationship_type": "causal", "source_pmcid": "PMC7147455" }, { "confidence": "medium", "disease": "Tracheitis", "glycan_involvement": "Glycosylation affects lysozyme stability and antimicrobial activity.", "mechanism": "Lysozyme in airway mucus helps defend against bacterial infection.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "protective", "source_pmcid": "PMC7147455" }, { "confidence": "medium", "disease": "Conjunctivitis", "glycan_involvement": "N-glycosylation modulates immunoglobulin effector functions.", "mechanism": "Immunoglobulins in tears and mucus neutralize pathogens causing conjunctivitis.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC7147455" }, { "confidence": "low", "disease": "Pericarditis", "glycan_involvement": "Glycosylation is critical for surfactant protein function and immune modulation.", "mechanism": "Surfactant proteins maintain alveolar stability and reduce infection risk.", "protein": "Pulmonary Surfactant Proteins", "relationship_type": "protective", "source_pmcid": "PMC7147455" }, { "confidence": "high", "disease": "Acute diarrhea", "glycan_involvement": "NSP4 is a glycoprotein; glycosylation is essential for its enterotoxin activity.", "mechanism": "NSP4 acts as a viral enterotoxin causing secretory diarrhea in rotavirus infection.", "protein": "NSP4", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11194" }, "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Guillain\u2013Barr\u00e9 syndrome", "glycan_involvement": "Glycan structures on LPS mediate cross-reactivity.", "mechanism": "Molecular mimicry between Campylobacter jejuni LPS ganglioside-like motifs and peripheral nerve gangliosides triggers autoimmunity.", "protein": "Ganglioside-like motif (LPS)", "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Typhoid fever", "glycan_involvement": "Vi antigen is a glycoprotein capsule; glycosylation is critical for immune evasion.", "mechanism": "Vi antigen is used for serotyping and diagnosis of Salmonella Typhi.", "protein": "Vi capsular antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7148607" }, { "confidence": "medium", "disease": "Viral gastroenteritis", "glycan_involvement": "VP6 is glycosylated, affecting antigenicity.", "mechanism": "VP6 is a group-specific antigen for rotavirus diagnosis.", "protein": "VP6", "relationship_type": "biomarker", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Acute diarrhea", "glycan_involvement": "LT is a glycoprotein; glycosylation affects toxin stability and host interaction.", "mechanism": "LT produced by ETEC stimulates cAMP-mediated chloride secretion.", "protein": "Heat-labile enterotoxin (LT)", "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Acute diarrhea", "glycan_involvement": "ST is a glycoprotein; glycosylation modulates activity.", "mechanism": "ST produced by ETEC stimulates cGMP-mediated chloride secretion.", "protein": "Heat-stable enterotoxin (ST)", "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Hemolytic uremic syndrome (HUS)", "glycan_involvement": "Shiga toxin binds to glycosylated Gb3 receptors on host cells.", "mechanism": "Shiga toxin from STEC and Shigella damages endothelial cells, leading to HUS.", "protein": "Shiga toxin", "protein_enriched": { "function": "The B subunit is responsible for the binding of the holotoxin to specific receptors on the target cell surface, such as globotriaosylceramide (Gb3) in human intestinal microvilli", "gene_name": "stxB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09386" }, "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "medium", "disease": "Yersinia sepsis", "glycan_involvement": "Glycosylation of siderophore-associated proteins may affect iron binding.", "mechanism": "Yersiniabactin enables iron acquisition, promoting Yersinia virulence and sepsis.", "protein": "Yersiniabactin", "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "medium", "disease": "Acute diarrhea", "glycan_involvement": "Glycosylation of fiber protein modulates host cell binding.", "mechanism": "Fiber protein mediates adenovirus attachment to enterocytes, causing diarrhea.", "protein": "Adenovirus fiber protein", "protein_enriched": { "function": "Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chapero", "gene_name": "L3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04133" }, "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "medium", "disease": "Infantile diarrhea", "glycan_involvement": "N-glycosylation of VP7 is required for proper folding and immune recognition.", "mechanism": "VP7 is a major envelope glycoprotein involved in rotavirus infectivity.", "protein": "Rotavirus VP7", "protein_enriched": { "function": "Accumulates harmlessly in the cytoplasmic membrane until it reaches a critical concentration that triggers the formation of micron-scale pores (holes) causing host cell membrane disruption and endolys", "gene_name": "14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11188" }, "relationship_type": "causal", "source_pmcid": "PMC7148607" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialic acid glycan recognition is essential for infection.", "mechanism": "HA binds sialic acid receptors on respiratory epithelial cells, mediating viral entry.", "protein": "Haemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Cleavage of sialylated glycans promotes spread.", "mechanism": "NA cleaves sialic acid from host glycoconjugates, facilitating viral release; targeted by antivirals.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation required for fusion activity.", "mechanism": "Fusion protein mediates syncytia formation in respiratory tract, leading to cell damage.", "protein": "Fusion protein (Paramyxoviridae)", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Targeted by palivizumab for prophylaxis in high-risk infants.", "protein": "RSV F glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Croup", "glycan_involvement": "Sialic acid glycan recognition and cleavage.", "mechanism": "HN glycoprotein mediates attachment and release via sialic acid binding and cleavage.", "protein": "Parainfluenza virus HN glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Infectious mononucleosis", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "gp350 binds CD21 on B cells, initiating infection.", "protein": "EBV gp350", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Burkitt's lymphoma", "glycan_involvement": "Glycosylation may affect immune evasion.", "mechanism": "Chronic EBV infection of B cells can drive oncogenesis.", "protein": "EBV gp350", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation required for infectivity.", "mechanism": "gB mediates entry into host cells, contributing to tissue tropism.", "protein": "CMV glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation modulates receptor interaction.", "mechanism": "gD binds host receptors, mediating CNS infection.", "protein": "HSV glycoprotein D (gD)", "protein_enriched": { "function": "In epithelial cells, the heterodimer gE/gI is required for the cell-to-cell spread of the virus, by sorting nascent virions to cell junctions. Once the virus reaches the cell junctions, virus particle", "gene_name": "gE", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04488" }, "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "medium", "disease": "Chickenpox/Shingles", "glycan_involvement": "Glycosylation required for infectivity.", "mechanism": "gE mediates viral entry and cell-to-cell spread.", "protein": "VZV glycoprotein E (gE)", "relationship_type": "causal", "source_pmcid": "PMC7148686" }, { "confidence": "high", "disease": "Lysosomal storage diseases", "glycan_involvement": "Glycosylation is essential for hydrolase stability and trafficking.", "mechanism": "Deficiency or malfunction of glycosylated lysosomal hydrolases leads to accumulation of undegraded substrates.", "protein": "Lysosomal hydrolases", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "high", "disease": "Cell injury (acute/chronic)", "glycan_involvement": "Glycosylation affects enzyme targeting and activity.", "mechanism": "Altered activity or release of hydrolases causes cellular damage.", "protein": "Lysosomal hydrolases", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Cell injury (acute/chronic)", "glycan_involvement": "Glycosylation stabilizes membrane proteins.", "mechanism": "Membrane glycoproteins maintain lysosomal integrity, preventing leakage of hydrolases.", "protein": "Lysosomal membrane glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation modulates inhibitor function.", "mechanism": "Inhibitors regulate hydrolase activity, limiting tissue damage during inflammation.", "protein": "Lysosomal hydrolase inhibitors", "relationship_type": "protective", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Tumor growth and metastasis", "glycan_involvement": "Altered glycosylation affects protein function and cell signaling.", "mechanism": "Aberrant secretion and processing of glycoproteins promote tumor progression.", "protein": "Secretory glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Metabolic disorders", "glycan_involvement": "Glycosylation required for enzyme activity.", "mechanism": "Impaired degradation of macromolecules disrupts metabolic homeostasis.", "protein": "Lysosomal hydrolases", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "low", "disease": "Iron overload disorders", "glycan_involvement": "Glycosylation may affect hydrolase stability under stress.", "mechanism": "Accumulation of iron in lysosomes impairs hydrolase function.", "protein": "Lysosomal hydrolases", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Lysosomal storage diseases", "glycan_involvement": "Glycosylation is critical for membrane protein function.", "mechanism": "Defective membrane glycoproteins disrupt lysosomal trafficking and fusion.", "protein": "Lysosomal membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Inflammation", "glycan_involvement": "Glycosylation regulates enzyme secretion.", "mechanism": "Excessive release of hydrolases contributes to tissue injury.", "protein": "Lysosomal hydrolases", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Cell injury (acute/chronic)", "glycan_involvement": "Glycosylation is required for proper folding and trafficking.", "mechanism": "Impaired processing of secretory glycoproteins affects cell survival.", "protein": "Secretory glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7149001" }, { "confidence": "medium", "disease": "Choroid plexus papilloma/carcinoma", "glycan_involvement": "Altered glycosylation may affect CSF protein composition.", "mechanism": "Neoplastic transformation of glycoprotein-secreting choroid plexus cells leads to tumor formation and CSF protein elevation.", "protein": "Choroid plexus glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7149320" }, { "confidence": "high", "disease": "CNS lymphoma", "glycan_involvement": "Glycosylation affects IgG stability and detection.", "mechanism": "Neoplastic lymphocytes secrete IgG, detected in CSF as a diagnostic marker.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149320" }, { "confidence": "medium", "disease": "Granulomatous meningoencephalomyelitis (GME)", "glycan_involvement": "Glycosylation modulates immunoglobulin function.", "mechanism": "Perivascular plasma cells secrete immunoglobulins, contributing to CSF protein elevation.", "protein": "Plasma cell immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC7149320" }, { "confidence": "medium", "disease": "Vascular encephalopathy", "glycan_involvement": "Glycosylation status may affect albumin transport.", "mechanism": "Albuminocytologic dissociation (elevated CSF protein with normal cell count) indicates blood-brain barrier disruption.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149320" }, { "confidence": "medium", "disease": "Vascular encephalopathy", "glycan_involvement": "Glycosylation affects fibrinogen solubility and function.", "mechanism": "Hyperfibrinogenemia contributes to hyperviscosity and risk of CNS infarction.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149320" }, { "confidence": "low", "disease": "Choroid plexus papilloma/carcinoma", "glycan_involvement": "Glycosylation pattern distinguishes CSF vs. serum transferrin.", "mechanism": "CSF transferrin isoforms may be altered in choroid plexus tumors.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149320" }, { "confidence": "medium", "disease": "Meningioma", "glycan_involvement": "Aberrant glycosylation promotes tumor progression.", "mechanism": "Meningioma cells express mucin-like glycoproteins, contributing to tumor growth and immune evasion.", "protein": "Mucin-like glycoproteins (meningioma)", "relationship_type": "causal", "source_pmcid": "PMC7149320" }, { "confidence": "high", "disease": "Infectious meningoencephalitis", "glycan_involvement": "Glycosylation critical for viral entry and pathogenesis.", "mechanism": "Viral glycoproteins mediate neuroinvasion and immune evasion.", "protein": "Glycoproteins of viral envelopes (e.g., rabies, distemper)", "relationship_type": "causal", "source_pmcid": "PMC7149320" }, { "confidence": "high", "disease": "Cryptococcal meningoencephalitis", "glycan_involvement": "Glycosylation essential for capsule function.", "mechanism": "Capsular glycoproteins protect fungus from host immunity and facilitate CNS invasion.", "protein": "Glycoproteins of fungal capsules (e.g., cryptococcus)", "relationship_type": "causal", "source_pmcid": "PMC7149320" }, { "confidence": "medium", "disease": "Astrocytoma/glioma", "glycan_involvement": "Aberrant glycosylation enhances invasiveness.", "mechanism": "Altered expression of cell adhesion glycoproteins promotes tumor invasion.", "protein": "Cell adhesion glycoproteins (astrocytoma/glioma)", "relationship_type": "causal", "source_pmcid": "PMC7149320" }, { "confidence": "high", "disease": "Equine Arteritis", "glycan_involvement": "Extensive glycosylation of GP5 masks neutralization epitopes, contributing to immune evasion and persistence.", "mechanism": "GP5 is essential for virus infectivity and assembly; major target of neutralizing antibodies.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "high", "disease": "Porcine Reproductive and Respiratory Syndrome (PRRS)", "glycan_involvement": "Glycosylation masks neutralization epitopes, delaying effective antibody response and promoting persistence.", "mechanism": "GP5 is required for PRRSV infectivity; main neutralization target.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "medium", "disease": "LDV-induced Poliomyelitis", "glycan_involvement": "Increased glycosylation reduces antibody binding, allowing neurovirulent variants to persist.", "mechanism": "GP5 glycosylation site number correlates with antibody binding and neurovirulence.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "medium", "disease": "Porcine Reproductive and Respiratory Syndrome (PRRS)", "glycan_involvement": "High heterogeneity in GP4 ectodomain glycosylation affects antibody recognition.", "mechanism": "GP4 contains a secondary neutralization epitope; involved in immune response.", "protein": "GP4", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "high", "disease": "Persistent Infection", "glycan_involvement": "N-glycosylation shields epitopes from antibody binding.", "mechanism": "Glycosylation of GP5 masks neutralization sites, promoting persistence in EAV, LDV, and PRRSV.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "medium", "disease": "Abortion in Horses", "glycan_involvement": "Glycosylation may affect virulence and immune evasion.", "mechanism": "GP5 is required for EAV infectivity, which causes abortion in pregnant mares.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "low", "disease": "Simian Hemorrhagic Fever", "glycan_involvement": "Likely similar glycosylation-mediated immune evasion.", "mechanism": "GP5 is required for SHFV infectivity; role inferred from EAV/PRRSV homology.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "medium", "disease": "Porcine Reproductive and Respiratory Syndrome (PRRS)", "glycan_involvement": "Glycosylation may affect immune recognition and virus assembly.", "mechanism": "GP3 is a minor glycoprotein required for infectivity; released in soluble form.", "protein": "GP3", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "medium", "disease": "Equine Arteritis", "glycan_involvement": "Glycosylation status not detailed, but implied to be important for function.", "mechanism": "GP2 is a minor glycoprotein required for infectivity.", "protein": "GP2", "relationship_type": "causal", "source_pmcid": "PMC7149349" }, { "confidence": "high", "disease": "Persistent Infection", "glycan_involvement": "Glycosylation impacts vaccine efficacy by masking epitopes.", "mechanism": "GP5 is the main target for neutralizing antibodies and vaccine development.", "protein": "GP5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149349" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity of HBsAg.", "mechanism": "HBsAg expressed in plants elicits protective immune response against hepatitis B virus.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity.", "mechanism": "Plant-expressed rabies glycoprotein induces immunity against rabies virus.", "protein": "Rabies virus glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "Norovirus infection", "glycan_involvement": "Capsid protein glycosylation may affect antigenicity.", "mechanism": "Plant-derived Norwalk virus capsid protein triggers immune response to norovirus.", "protein": "Norwalk virus capsid protein", "protein_enriched": { "function": "Capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry, about 38 nm in diameter, and consisting of 180 capsid proteins (PubMed:10514371). A smaller form of capsid with a diame", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q83884" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "high", "disease": "Diarrhea (E. coli)", "glycan_involvement": "Glycosylation influences stability and immunogenicity.", "mechanism": "LT-B expressed in plants stimulates mucosal immunity against E. coli enterotoxin.", "protein": "E. coli heat-labile enterotoxin B subunit (LT-B)", "protein_enriched": { "function": "The biological activity of the toxin is produced by the A chain, which activates intracellular adenyl cyclase", "gene_name": "eltB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P32890" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "high", "disease": "Cholera", "glycan_involvement": "Glycosylation modulates receptor binding and immune response.", "mechanism": "Plant-derived cholera toxin B subunit induces protective antibodies.", "protein": "Cholera toxin B subunit", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "Swine transmissible gastroenteritis", "glycan_involvement": "Glycosylation critical for antigenicity.", "mechanism": "Plant-expressed viral glycoproteins elicit immunity in swine.", "protein": "Glycoproteins of swine-transmissible gastroenteritis coronavirus", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Extensive glycosylation affects antigenicity and immune evasion.", "mechanism": "Plant-expressed HIV-1 antigens induce immune response.", "protein": "HIV-1 antigen (gp120/gp41)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may influence immunogenicity.", "mechanism": "Oral delivery of plant-expressed GAD may induce tolerance and prevent autoimmunity.", "protein": "Mouse glutamate decarboxylase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "Foot and mouth disease", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Plant-derived VPI protein used for veterinary vaccination.", "protein": "VPI protein of foot and mouth disease virus", "protein_enriched": { "function": "Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03302" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "medium", "disease": "Japanese cedar pollinosis (allergy)", "glycan_involvement": "Glycosylation may modulate peptide stability and immune recognition.", "mechanism": "Oral delivery of allergen peptides in rice suppresses allergic Th2 response.", "protein": "Japanese cedar pollen allergen T-cell epitope peptides", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149355" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation shields neutralizing epitopes, facilitating immune evasion.", "mechanism": "gp160 mediates viral entry via CD4 and coreceptor binding; subject to immune escape mutations.", "protein": "gp160", "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and receptor binding.", "mechanism": "HA mediates viral attachment and entry; antigenic drift leads to immune escape.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield impedes antibody access.", "mechanism": "gp120 is targeted by neutralizing antibodies and drugs; escape mutants arise.", "protein": "gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149360" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation affects epitope exposure.", "mechanism": "gp41 mediates membrane fusion; targeted by some neutralizing antibodies.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149360" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation at V1/V2 modulates antibody recognition.", "mechanism": "V1/V2 loop is a major site of immune escape and diversity.", "protein": "V1/V2 loop (HIV Env)", "relationship_type": "biomarker", "source_pmcid": "PMC7149360" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Specific glycan structures are critical for antibody binding.", "mechanism": "V3 loop glycan is a target for broadly neutralizing antibodies.", "protein": "Glycan-V3 (HIV Env)", "relationship_type": "biomarker", "source_pmcid": "PMC7149360" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Spike protein mediates host cell entry and cross-species transmission.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation shields E2 from immune recognition.", "mechanism": "E2 mediates viral entry and is a major target of neutralizing antibodies.", "protein": "Hepatitis C E2 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "low", "disease": "Monkeypox", "glycan_involvement": "Glycosylation may affect host range and immune evasion.", "mechanism": "Envelope glycoprotein mediates host cell entry.", "protein": "Monkeypox envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "medium", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation modulates immune recognition and virulence.", "mechanism": "Ebola glycoprotein mediates host cell entry and pathogenesis.", "protein": "Ebola glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7149360" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavy N-glycosylation shields gp120 from immune recognition and affects receptor binding.", "mechanism": "gp120 binds CD4 and CCR5/CXCR4 to mediate viral entry; targeted by attachment inhibitors and neutralizing antibodies.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation modulates gp41 structure and immune evasion.", "mechanism": "gp41 mediates fusion of viral and host membranes; targeted by fusion inhibitor enfuvirtide.", "protein": "HIV envelope glycoprotein gp41", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects HA folding, antigenicity, and receptor binding.", "mechanism": "HA mediates viral attachment and fusion; targeted by amantadine (indirectly) and neutralizing antibodies.", "protein": "Influenza virus hemagglutinin (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation influences NA enzymatic activity and immune recognition.", "mechanism": "NA cleaves sialic acids to release virions; targeted by neuraminidase inhibitors (e.g., oseltamivir).", "protein": "Influenza virus neuraminidase (NA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "O-glycosylation and N-glycosylation modulate CCR5 surface expression and ligand binding.", "mechanism": "CCR5 is required for HIV entry; blocked by maraviroc.", "protein": "HIV co-receptor CCR5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation affects CD4 folding and interaction with gp120.", "mechanism": "CD4 is the primary receptor for HIV gp120; soluble CD4 can block viral attachment.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "medium", "disease": "Herpes simplex infection", "glycan_involvement": "Glycosylation may affect TK stability and activity (not detailed in article).", "mechanism": "Viral TK phosphorylates acyclovir, activating it to inhibit viral DNA polymerase.", "protein": "Herpesvirus thymidine kinase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03176" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) infection", "glycan_involvement": "Possible glycosylation may affect kinase activity (not detailed in article).", "mechanism": "UL97 phosphorylates ganciclovir, activating it to inhibit viral DNA polymerase.", "protein": "CMV UL97 kinase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "No direct glycosylation involvement; protease activity affects glycoprotein processing.", "mechanism": "HIV protease cleaves viral polyproteins; inhibitors block maturation of infectious virions.", "protein": "HIV protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation of HBV envelope proteins affects viral assembly and infectivity.", "mechanism": "Viral DNA polymerase is inhibited by nucleoside/nucleotide analogs (e.g., lamivudine, tenofovir).", "protein": "Hepatitis B virus DNA polymerase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149393" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates virus entry by binding to host cell receptors, essential for infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation critical for proper folding and function.", "mechanism": "Mediates virus entry by binding to host cell receptors, essential for infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "N-glycosylation affects antigenicity and host interaction.", "mechanism": "Facilitates entry of common cold HCoVs into host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Potential glycosylation may affect assembly, but not detailed in article.", "mechanism": "Involved in virus assembly and release; essential for virion morphogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "N-glycosylation implicated in virion assembly and immune evasion.", "mechanism": "Major structural protein, essential for virion assembly.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "N-glycosylation modulates host immune response.", "mechanism": "Entry protein for HCoVs causing pneumonia.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "Bronchitis", "glycan_involvement": "N-glycosylation modulates host immune response.", "mechanism": "Entry protein for HCoVs causing bronchitis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "low", "disease": "Pneumonia", "glycan_involvement": "Not specified.", "mechanism": "Contributes to virion assembly in pneumonia-causing HCoVs.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "N-glycosylation may affect assembly and immune evasion.", "mechanism": "Essential for virion assembly in MERS-CoV.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Binds viral RNA genome, essential for packaging.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "causal", "source_pmcid": "PMC7149517" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation of S protein is essential for proper folding, receptor binding, and immune evasion.", "mechanism": "MERS-CoV S glycoprotein mediates viral entry by binding to DPP4 on host cells, initiating infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149527" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "DPP4 is a glycoprotein; its glycosylation may affect receptor accessibility and virus binding.", "mechanism": "DPP4 acts as the cellular receptor for MERS-CoV S glycoprotein, enabling viral attachment and entry.", "protein": "Dipeptidyl peptidase 4 (DPP4/CD26)", "relationship_type": "causal", "source_pmcid": "PMC7149527" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation of S protein modulates host immune recognition and pathogenesis.", "mechanism": "Viral entry via S glycoprotein-DPP4 interaction leads to respiratory cell infection and pneumonia.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149527" }, { "confidence": "high", "disease": "Acute necrotizing enteritis in harbor seals", "glycan_involvement": "Glycosylation of S protein is essential for receptor binding and fusion", "mechanism": "Mediates viral attachment and entry into host intestinal cells", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "high", "disease": "Syncytia formation in infected tissues", "glycan_involvement": "Glycosylation modulates fusogenic activity", "mechanism": "Induces cell-cell fusion leading to syncytia", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "medium", "disease": "Respiratory, gastrointestinal, cardiovascular, neurological diseases (general)", "glycan_involvement": "Glycosylation required for receptor interaction", "mechanism": "Mediates receptor binding and erythrocyte agglutination in Betacoronaviruses", "protein": "Hemagglutinin-esterase (HE) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "medium", "disease": "Viral infection (general)", "glycan_involvement": "Glycosylation contributes to core stability and assembly", "mechanism": "Central role in viral assembly and budding", "protein": "Matrix (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "medium", "disease": "Acute hepatic necrosis in beluga whale", "glycan_involvement": "Glycosylation critical for host cell tropism", "mechanism": "Mediates entry into hepatic cells", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "medium", "disease": "Hemorrhagic disease in cyprinids", "glycan_involvement": "Glycosylation required for infectivity", "mechanism": "Mediates viral entry into fish epithelial/endothelial cells", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "high", "disease": "Respiratory, gastrointestinal, cardiovascular, neurological diseases (general)", "glycan_involvement": "Glycosylation modulates tissue tropism", "mechanism": "Attachment and fusion with host cells in multiple tissues", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149540" }, { "confidence": "high", "disease": "Viral infection (general)", "glycan_involvement": "Glycosylation affects antigenicity", "mechanism": "Major antigen inducing neutralizing antibodies", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149540" }, { "confidence": "medium", "disease": "Viral infection (general)", "glycan_involvement": "Glycosylation required for antigenicity", "mechanism": "Major antigen inducing immune response", "protein": "Hemagglutinin-esterase (HE) glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7149540" }, { "confidence": "low", "disease": "Viral infection (general)", "glycan_involvement": "Glycosylation may affect immune recognition", "mechanism": "Structural protein, target for immune response", "protein": "Matrix (M) glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7149540" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects ApoE structure and lipid binding, influencing amyloid clearance.", "mechanism": "APOE-\u025b4 allele increases risk and accelerates amyloid deposition and neurodegeneration; APOE-\u025b2 is protective.", "protein": "Apolipoprotein E (ApoE)", "protein_enriched": { "function": "APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754", "gene_name": "APOE", "glycan_count": 7, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G57321FI", "G29068FM", "G29931IJ", "G43417UB", "G53434XO", "G63628AV", "G49108TO" ], "uniprot_id": "P02649" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP processing and A\u03b2 generation.", "mechanism": "APP mutations lead to increased A\u03b2 production and plaque formation.", "protein": "Amyloid beta precursor protein (APP)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Heavily glycosylated; glycan structure affects chaperone activity and A\u03b2 binding.", "mechanism": "CLU variants associated with AD risk; involved in A\u03b2 clearance and neuroprotection.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker/protective", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation impacts CR1 function in complement activation.", "mechanism": "CR1 polymorphisms linked to AD risk; modulates immune response and A\u03b2 clearance.", "protein": "Complement receptor 1 (CR1)", "protein_enriched": { "function": "Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). Mediates the bi", "gene_name": "CR1", "glycan_count": 13, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G22310AV", "G40834TG", "G45395BF", "G47748JZ", "G48414YA", "G54285KU", "G57888GL", "G82830MN", "G06356OH", "G27058EU", "G79666IR", "G86795LJ", "G49108TO" ], "uniprot_id": "P17927" }, "relationship_type": "risk/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sialylated glycan motifs regulate CD33 signaling and microglial activity.", "mechanism": "CD33 variants impair microglial A\u03b2 clearance, increasing AD risk.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "risk/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation required for LRP1 trafficking and ligand binding.", "mechanism": "LRP1 mediates A\u03b2 transport across BBB; reduced expression leads to A\u03b2 accumulation.", "protein": "Low-density lipoprotein receptor-related protein 1 (LRP1)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates RAGE ligand binding and signaling.", "mechanism": "RAGE mediates A\u03b2-induced inflammation and neurotoxicity.", "protein": "Receptor for advanced glycation end products (RAGE)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation essential for P-gp stability and function.", "mechanism": "P-gp exports A\u03b2 from brain; reduced expression increases A\u03b2 accumulation.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation affects TTR stability and A\u03b2 binding.", "mechanism": "TTR binds A\u03b2 and inhibits aggregation; CSF levels altered in AD.", "protein": "Transthyretin (TTR)", "protein_enriched": { "function": "Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain", "gene_name": "TTR", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P02766" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC7149555" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation modulates haptoglobin function and clearance.", "mechanism": "CSF haptoglobin levels differ in AD; involved in oxidative stress response.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149555" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Cleavage of sialylated glycans on host cell surface.", "mechanism": "Neuraminidase cleaves sialic acid residues to release virus; inhibitors block viral spread.", "protein": "Influenza neuraminidase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Mediates viral entry by binding CD4 and chemokine receptors; targeted by entry/fusion inhibitors.", "protein": "HIV-1 envelope glycoprotein (gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosaminoglycan chains mediate virus binding.", "mechanism": "Serve as initial attachment sites for many viruses including HSV.", "protein": "Heparan sulphate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC7149618" }, { "confidence": "medium", "disease": "Respiratory viral infections", "glycan_involvement": "Glycosaminoglycan chains mediate virus binding.", "mechanism": "Serve as attachment sites for respiratory viruses.", "protein": "Heparan sulphate proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC7149618" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation affects receptor conformation and virus binding.", "mechanism": "Primary receptor for HIV-1 entry.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation modulates receptor function and virus interaction.", "mechanism": "Coreceptor for HIV-1 entry; blocked by maraviroc.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation modulates receptor function and virus interaction.", "mechanism": "Alternative coreceptor for HIV-1 entry.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "Neutralize virus by binding surface glycoproteins.", "protein": "Immunoglobulins (antibodies)", "relationship_type": "protective", "source_pmcid": "PMC7149618" }, { "confidence": "low", "disease": "Respiratory viral infections", "glycan_involvement": "Glycosylation status may affect charge and binding.", "mechanism": "Polyanionic albumins can block viral attachment.", "protein": "Albumin (negatively charged)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149618" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycan shield affects detection and immune response.", "mechanism": "Presence indicates active viral infection.", "protein": "HIV-1 envelope glycoprotein (gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149618" }, { "confidence": "high", "disease": "Viral infections (general)", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "Presents viral peptides to cytotoxic T lymphocytes for infected cell clearance.", "protein": "Class I Major Histocompatibility Complex (MHC) protein", "relationship_type": "protective", "source_pmcid": "PMC7149636" }, { "confidence": "high", "disease": "Persistent viral infection", "glycan_involvement": "Altered glycosylation can affect MHC I trafficking and immune recognition.", "mechanism": "Viruses downregulate MHC I to evade CTL killing, promoting persistence.", "protein": "Class I Major Histocompatibility Complex (MHC) protein", "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "medium", "disease": "Persistent viral infection", "glycan_involvement": "Mimic host glycosylation to avoid immune surveillance.", "mechanism": "Viral homologs bind \u03b22-microglobulin and peptides but do not activate CTLs, blocking immune detection.", "protein": "Viral MHC class I homologs", "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "high", "disease": "Vaccine failure", "glycan_involvement": "N-glycosylation essential for peptide loading and surface expression.", "mechanism": "Impaired MHC II expression or function reduces T cell help and antibody responses.", "protein": "Class II Major Histocompatibility Complex (MHC) protein", "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "medium", "disease": "Failure of antiviral immunity", "glycan_involvement": "Glycosylation affects trafficking and stability.", "mechanism": "Invariant chain guides MHC II trafficking; disruption impairs antigen presentation.", "protein": "Invariant chain (CD74)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "high", "disease": "Viral infections (general)", "glycan_involvement": "N-glycosylation required for receptor function and cell surface localization.", "mechanism": "Mediates antiviral signaling upon IFN binding.", "protein": "Interferon alpha/beta receptor (IFNAR)", "relationship_type": "protective", "source_pmcid": "PMC7149636" }, { "confidence": "high", "disease": "Immunodeficiency (due to viral evasion)", "glycan_involvement": "Glycosylation modulates receptor-virus interactions.", "mechanism": "Viruses (e.g., HIV) target CD4+ cells, leading to immune suppression.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "medium", "disease": "Viral infections (general)", "glycan_involvement": "Glycosylation affects Fc binding and receptor function.", "mechanism": "Mediates antibody-dependent cellular cytotoxicity by NK cells.", "protein": "CD16 (Fc\u03b3RIII)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7149636" }, { "confidence": "medium", "disease": "Persistent viral infection", "glycan_involvement": "Mimic host glycosylation to evade detection.", "mechanism": "Viral glycoproteins bind and neutralize host cytokines, blocking immune signaling.", "protein": "Viral cytokine receptor homologs", "relationship_type": "causal", "source_pmcid": "PMC7149636" }, { "confidence": "low", "disease": "Tumor development (virus-induced)", "glycan_involvement": "Glycosylation modulates ligand binding and immune interactions.", "mechanism": "Altered ICAM-1 expression can affect immune cell adhesion and tumor immune evasion.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149636" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation of CD4 affects HIV binding affinity.", "mechanism": "HIV binds CD4 glycoprotein for cell entry, leading to immune cell depletion.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates receptor function and viral tropism.", "mechanism": "CCR5 acts as a co-receptor for HIV entry into T cells.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "N-glycosylation required for proper surface expression and antigen presentation.", "mechanism": "HBV downregulates MHC I glycoproteins to evade CTL-mediated clearance.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Herpes simplex stromal keratitis", "glycan_involvement": "Glycosylation influences antigen presentation and T cell activation.", "mechanism": "HSV infection leads to chronic CD4+ T cell-mediated inflammation via MHC II presentation.", "protein": "MHC class II", "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Respiratory syncytial virus (RSV)-induced pulmonary lesions", "glycan_involvement": "O-glycosylation critical for mucosal transport and stability.", "mechanism": "Secretory IgA neutralizes RSV at mucosal surfaces, limiting infection.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Dengue hemorrhagic fever", "glycan_involvement": "Fc glycosylation affects Fc receptor binding and immune activation.", "mechanism": "IgG mediates antibody-dependent enhancement, worsening disease.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Glomerulonephritis (HBV)", "glycan_involvement": "Glycosylation required for complement activation and immune complex formation.", "mechanism": "Immune complexes containing HBV antigens and complement deposit in glomeruli, causing damage.", "protein": "Complement proteins (C3)", "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation shields gp120 from neutralizing antibodies.", "mechanism": "gp120 mediates viral attachment to CD4 and CCR5, facilitating entry.", "protein": "Viral envelope glycoproteins (HIV gp120)", "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation modulates antigenicity and immune evasion.", "mechanism": "HA glycoprotein binds sialic acid on host cells, mediating entry.", "protein": "Viral envelope glycoproteins (Influenza HA)", "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation of MOG influences antigenicity and autoimmune targeting.", "mechanism": "Viral infection may trigger immune response against MOG, leading to demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC7149641" }, { "confidence": "high", "disease": "Bacterial infection (e.g., Salmonella, E. coli)", "glycan_involvement": "GPI-anchor and glycosylation may affect surface localization and binding.", "mechanism": "GP2 on M cells acts as a receptor for type I piliated bacteria, facilitating their entry into Peyer's patches.", "protein": "Glycoprotein 2 (GP2)", "protein_enriched": { "function": "Functions as an intestinal M-cell transcytotic receptor specific for type-I-piliated bacteria that participates in the mucosal immune response toward these bacteria. At the apical membrane of M-cells ", "gene_name": "GP2", "glycan_count": 8, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G11314AS", "G36379GD", "G57317CE", "G05724UK", "G06110VR", "G20210JR", "G23294PN", "G62765YT" ], "uniprot_id": "P55259" }, "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "medium", "disease": "Bacterial infection (E. coli)", "glycan_involvement": "GPI-anchor and glycosylation influence receptor function.", "mechanism": "Uromodulin on M cells binds type I piliated E. coli, aiding bacterial translocation.", "protein": "Uromodulin", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "medium", "disease": "Brucellosis", "glycan_involvement": "GPI-anchor and glycosylation affect prion protein localization and function.", "mechanism": "PrPc on M cells binds Brucella abortus Hsp60, promoting bacterial internalization.", "protein": "Cellular prion protein (PrPc)", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "medium", "disease": "Clostridium perfringens enterotoxemia", "glycan_involvement": "Glycosylation may modulate Claudin 4 conformation and binding.", "mechanism": "Clostridium perfringens enterotoxin binds Claudin 4 in M cells, facilitating toxin entry.", "protein": "Claudin 4", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "low", "disease": "Bacterial infection (Gram-negative bacteria)", "glycan_involvement": "Glycosylation may affect ligand binding.", "mechanism": "ANXA5 binds lipid A of LPS, facilitating uptake of Gram-negative bacteria by M cells.", "protein": "ANXA5", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "low", "disease": "Bacterial infection", "glycan_involvement": "Glycosylation may influence receptor function.", "mechanism": "PGLRP-1 on M cells binds bacterial peptidoglycans, aiding antigen sampling and possible pathogen entry.", "protein": "PGLRP-1", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "medium", "disease": "Yersiniosis", "glycan_involvement": "Glycosylation may affect receptor accessibility.", "mechanism": "Yersinia OmpH \u03b21\u03b11 peptide binds C5aR on M cells, enhancing bacterial uptake.", "protein": "C5aR (CD88)", "relationship_type": "causal", "source_pmcid": "PMC7149644" }, { "confidence": "high", "disease": "Chronic/acute intestinal inflammation", "glycan_involvement": "O-glycosylation is essential for barrier function.", "mechanism": "Mucins form a glycosylated barrier, limiting microbial invasion and inflammation.", "protein": "Mucin (general)", "relationship_type": "protective", "source_pmcid": "PMC7149644" }, { "confidence": "high", "disease": "Chronic/acute intestinal inflammation", "glycan_involvement": "Glycosylation critical for IgA stability and function in mucosa.", "mechanism": "IgA produced in GALT neutralizes pathogens and maintains tolerance to commensals.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC7149644" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Glycosylation modulates integrin-ligand interactions.", "mechanism": "\u03b14\u03b27 mediates lymphocyte homing to gut; blockade impairs lymphoid tissue formation and reduces colitis.", "protein": "Integrin \u03b14\u03b27", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149644" }, { "confidence": "high", "disease": "Membranoproliferative glomerulonephritis type 2", "glycan_involvement": "C3 glycosylation affects stability and function in complement activation.", "mechanism": "C3 nephritic factor stabilizes C3 convertase, leading to complement overactivation and glomerular damage.", "protein": "C3", "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "medium", "disease": "Partial lipodystrophy", "glycan_involvement": "Glycosylation modulates C3 function and immune recognition.", "mechanism": "C3 nephritic factor leads to abnormal complement activation, contributing to fat loss.", "protein": "C3", "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Carcinoma", "glycan_involvement": "N-glycosylation is critical for E-cadherin stability and cell-cell adhesion.", "mechanism": "Mutations or loss of E-cadherin disrupt cell adhesion, promoting tumor invasion.", "protein": "Cadherin-1 (E-cadherin)", "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "medium", "disease": "Hypotrichosis with juvenile macular dystrophy", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Defects in P-cadherin impair cell adhesion in hair and retina.", "protein": "Cadherin-3 (P-cadherin)", "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "medium", "disease": "EEM syndrome", "glycan_involvement": "Glycosylation affects trafficking and adhesion properties.", "mechanism": "Mutations in P-cadherin gene cause multisystem developmental defects.", "protein": "Cadherin-3 (P-cadherin)", "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Protein misfolding diseases", "glycan_involvement": "Binds N-glycans on nascent proteins to assist folding.", "mechanism": "Acts as ER chaperone, ensuring proper folding of glycoproteins.", "protein": "Calnexin", "relationship_type": "protective", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Protein misfolding diseases", "glycan_involvement": "Recognizes N-glycans on folding intermediates.", "mechanism": "ER chaperone that binds glycoproteins, preventing misfolding and aggregation.", "protein": "Calreticulin", "protein_enriched": { "function": "", "gene_name": "CALR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "A0A7P0T861" }, "relationship_type": "protective", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Infection (bacterial/yeast)", "glycan_involvement": "Recognizes fucose/mannose-rich glycans on pathogens.", "mechanism": "Binds microbial glycans, promoting opsonization and clearance.", "protein": "Collectin-11", "relationship_type": "protective", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Infection (bacterial/yeast)", "glycan_involvement": "Direct recognition of pathogen glycans.", "mechanism": "Binds mannose-rich glycans on pathogens, activates lectin pathway of complement.", "protein": "Mannan-binding protein (MBL)", "relationship_type": "protective", "source_pmcid": "PMC7149705" }, { "confidence": "medium", "disease": "Immune complex disease", "glycan_involvement": "Glycosylation modulates C1q binding to IgG and immune complexes.", "mechanism": "C1q binds immune complexes, triggering complement activation and inflammation.", "protein": "C1q", "protein_enriched": { "function": "Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pat", "gene_name": "C1QA", "glycan_count": 47, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G04854VP", "G06356OH", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G15664MX", "G20706XG", "G22310AV", "G23863VK", "G24528MX", "G25079LO", "G27058EU", "G27126ED", "G28541PG", "G40574BA", "G40834TG", "G40926MX", "G43669FQ", "G45395BF", "G46691LC", "G48414YA", "G59324HL", "G59626AS", "G61256FT", "G62765YT", "G67164EE", "G70619PT", "G72747WU", "G77669RF", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G83460ZZ", "G83555HU", "G84452RH", "G86752LQ", "G87123QX", "G88374WZ", "G90659AW", "G92551JA", "G94470IW" ], "uniprot_id": "P02745" }, "relationship_type": "causal", "source_pmcid": "PMC7149705" }, { "confidence": "high", "disease": "Congenital hepatic fibrosis", "glycan_involvement": "CK7 is a glycoprotein; glycosylation may affect filament stability and cell signaling.", "mechanism": "CK7 marks ductal plate cells and proliferating bile ductules in ductal plate malformations.", "protein": "Cytokeratin 7", "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "high", "disease": "Congenital hepatic fibrosis", "glycan_involvement": "Glycosylation may modulate filament assembly and cell interactions.", "mechanism": "CK19 marks biliary phenotype in hepatic progenitor cells and ductular reactions.", "protein": "Cytokeratin 19", "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Fibronectin glycosylation regulates ECM assembly and cell adhesion.", "mechanism": "Increased fibronectin deposition by activated stellate cells contributes to fibrotic ECM.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC7149729" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Laminin glycosylation affects cell-matrix interactions and signaling.", "mechanism": "Laminin is upregulated in fibrotic matrix, promoting basement membrane-like structures.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149729" }, { "confidence": "medium", "disease": "Chronic liver disease", "glycan_involvement": "Recognizes terminal galactose on glycoproteins; altered glycosylation affects receptor binding.", "mechanism": "Loss or dysfunction impairs clearance of desialylated glycoproteins, reflecting hepatocyte injury.", "protein": "Asialoglycoprotein receptor", "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "IgA glycosylation modulates secretion and immune function.", "mechanism": "IgA is secreted by cholangiocytes; increased in bile during cholestatic disease.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects collagen IV assembly and ECM structure.", "mechanism": "Excess collagen IV deposition forms abnormal basement membrane in fibrotic liver.", "protein": "Collagen type IV", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A1", "glycan_count": 2, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G43417UB" ], "uniprot_id": "P02462" }, "relationship_type": "causal", "source_pmcid": "PMC7149729" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosaminoglycan chains are central to proteoglycan function.", "mechanism": "Increased proteoglycan deposition alters ECM composition in fibrosis.", "protein": "Proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC7149729" }, { "confidence": "medium", "disease": "Biliary disease", "glycan_involvement": "Glycosylation may affect enzyme stability and localization.", "mechanism": "Increased expression in cholangiocytes during biliary injury.", "protein": "\u03b3-Glutamyltranspeptidase", "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "medium", "disease": "Von Meyenburg complexes", "glycan_involvement": "Glycosylation modulates ECM interactions.", "mechanism": "Fibronectin is present in the ECM of hamartomatous lesions.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC7149729" }, { "confidence": "high", "disease": "Bovine herpesvirus type 1 infection (IBR)", "glycan_involvement": "gE is a glycosylated envelope protein essential for viral infectivity and immune recognition", "mechanism": "gE-deleted marker vaccines allow differentiation of infected from vaccinated animals (DIVA)", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects immunogenicity and proper folding of G protein", "mechanism": "G protein is the main antigen in recombinant and edible vaccines, inducing protective immunity", "protein": "Rabies virus glycoprotein G", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Bovine viral diarrhea", "glycan_involvement": "N-glycosylation of E2 is critical for antigenicity and immune response", "mechanism": "E2 is the major immunogenic glycoprotein used in subunit and DNA vaccines", "protein": "Bovine viral diarrhea virus glycoprotein E2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "medium", "disease": "Foot and mouth disease", "glycan_involvement": "Glycosylation may influence antigenicity and vaccine efficacy", "mechanism": "VP1 is a capsid glycoprotein used in subunit vaccines to induce neutralizing antibodies", "protein": "Foot-and-mouth disease virus VP1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "N-glycosylation is important for folding and immunogenicity", "mechanism": "E protein is the main antigen in subunit vaccines, eliciting protective immunity", "protein": "Japanese encephalitis virus E envelope protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Newcastle disease", "glycan_involvement": "Glycosylation is required for proper folding and immune recognition", "mechanism": "HN glycoprotein is used in subunit vaccines to induce protective immunity", "protein": "Newcastle disease virus hemagglutinin-neuraminidase (HN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "medium", "disease": "Porcine circovirus disease", "glycan_involvement": "Glycosylation may affect immunogenicity", "mechanism": "Cap protein is the main immunogen in subunit vaccines", "protein": "Porcine circovirus type 2 Cap protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Brucellosis", "glycan_involvement": "O-antigen is a polysaccharide critical for immune evasion and vaccine differentiation", "mechanism": "O-antigen is a major surface glycan; absence in RB-51 strain allows DIVA strategy", "protein": "Brucella abortus O-antigen of LPS", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Escherichia coli infection (colibacillosis)", "glycan_involvement": "Fimbrial glycoproteins mediate attachment to host glycan receptors", "mechanism": "F5 fimbrial adhesin is used in vaccines to prevent ETEC colonization", "protein": "Escherichia coli F5 adhesin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "medium", "disease": "Leptospirosis", "glycan_involvement": "Glycosylation may affect antigenicity and immune response", "mechanism": "Outer membrane glycoproteins are targets for recombinant vaccine development", "protein": "Leptospira outer membrane proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149732" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Mutations in S protein alter tropism to macrophages, enabling systemic infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "Infectious bronchitis (chicken)", "glycan_involvement": "Glycosylation modulates antigenicity and host range.", "mechanism": "S protein mediates attachment to respiratory epithelium and determines tissue tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "medium", "disease": "Mouse hepatitis", "glycan_involvement": "HE binds sialic acids; glycosylation critical for function.", "mechanism": "HE facilitates virus entry and spread in host tissues.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation of S protein modulates receptor binding and immune recognition.", "mechanism": "S protein binds ACE2 receptor, mediating entry into human cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation influences receptor interaction and immune escape.", "mechanism": "S protein binds DPP4 receptor, determining host tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "Porcine epidemic diarrhea", "glycan_involvement": "Glycosylation affects receptor specificity and viral infectivity.", "mechanism": "S protein binds APN receptor, mediating infection of enterocytes.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "medium", "disease": "Infectious bronchitis (chicken)", "glycan_involvement": "O-glycosylation (in some strains) affects intracellular trafficking and assembly.", "mechanism": "M protein essential for virion assembly and budding.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "medium", "disease": "Canine coronavirus gastroenteritis", "glycan_involvement": "Glycosylation modulates host specificity.", "mechanism": "S protein mediates entry into enterocytes via APN receptor.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "medium", "disease": "Bovine coronavirus enteritis", "glycan_involvement": "Glycosylation influences receptor binding and immune evasion.", "mechanism": "S protein binds sialic acids and other receptors for enteric infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "Avian infectious bronchitis", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "S protein is the main target for neutralizing antibodies and vaccine design.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149743" }, { "confidence": "high", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation of S is essential for proper folding, receptor binding, and immune evasion.", "mechanism": "Mediates viral entry into host respiratory epithelial cells via receptor binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "high", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation in S1 affects antigenicity and serotype specificity.", "mechanism": "S1 subunit determines host cell tropism and is the main target for neutralizing antibodies.", "protein": "Spike S1 subunit", "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "high", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation sites in S1 may influence epitope presentation.", "mechanism": "S1 gene sequence variation is used for molecular diagnosis and serotyping of IBV strains.", "protein": "Spike S1 subunit", "relationship_type": "biomarker", "source_pmcid": "PMC7149748" }, { "confidence": "high", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation modulates immunogenicity and vaccine efficacy.", "mechanism": "S1 is the major immunogen for vaccine development; mutations in S1 lead to vaccine escape.", "protein": "Spike S1 subunit", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149748" }, { "confidence": "medium", "disease": "Nephropathogenic IB", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Specific S1 variants confer renal tropism and increased pathogenicity.", "protein": "Spike S1 subunit", "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "medium", "disease": "Reproductive tract IB", "glycan_involvement": "Glycosylation may affect tissue targeting.", "mechanism": "S1 sequence variation linked to reproductive tract infection and pathology.", "protein": "Spike S1 subunit", "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "medium", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation contributes to antigenicity.", "mechanism": "Conserved antigenic epitopes used in serological assays for IBV detection.", "protein": "Membrane glycoprotein (M)", "relationship_type": "biomarker", "source_pmcid": "PMC7149748" }, { "confidence": "medium", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Glycosylation stabilizes S2 structure.", "mechanism": "S2 anchors S1 to the membrane and mediates membrane fusion during viral entry.", "protein": "Spike S2 subunit", "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "low", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Minor glycosylation may affect immune recognition.", "mechanism": "Conserved protein used in some diagnostic assays.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149748" }, { "confidence": "high", "disease": "Infectious bronchitis (IB)", "glycan_involvement": "Altered glycosylation patterns may contribute to immune escape.", "mechanism": "Mutations and recombination in S (especially S1) drive emergence of new IBV variants and serotypes.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149748" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects folding, receptor binding, and immune evasion.", "mechanism": "Mediates viral entry via binding to ACE2 receptor; determines host specificity and pathogenesis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor interaction and immune escape.", "mechanism": "Mediates viral entry via binding to DPP4 receptor; key determinant of host range and pathogenicity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation critical for receptor binding and antigenicity.", "mechanism": "S protein binds \u03b1-2,3-linked sialic acid for host cell attachment; determines tissue tropism and serotype.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "medium", "disease": "Feline Infectious Peritonitis", "glycan_involvement": "Glycosylation influences host range and cell entry.", "mechanism": "Substitution of S protein from murine virus enables cross-species infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "medium", "disease": "Murine Hepatitis", "glycan_involvement": "Glycosylation impacts receptor binding and immune evasion.", "mechanism": "S protein mutations alter host range and tissue tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation affects function and host interaction.", "mechanism": "Present in some beta-CoVs; involved in viral entry and spread.", "protein": "Hemagglutinin esterase (HE)", "relationship_type": "causal", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation of DPP4 may modulate virus-receptor interaction.", "mechanism": "Host glycoprotein receptor for MERS-CoV S protein; essential for viral entry.", "protein": "Dipeptidyl peptidase 4 (DPP4/CD26)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation of ACE2 influences S protein binding.", "mechanism": "Host glycoprotein receptor for SARS-CoV S protein; determines susceptibility.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation status may affect antigenicity and immune recognition.", "mechanism": "Mutations in S1 domain (RBD) correlate with epidemic strains and host adaptation.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation affects antigenic properties and vaccine efficacy.", "mechanism": "S1 sequence identity determines serotype and cross-protection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7149750" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation required for proper folding and immune evasion.", "mechanism": "Mediates viral fusion and entry, leading to epithelial cell damage and airway obstruction.", "protein": "RSV F protein", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Heavily glycosylated; glycan moieties mediate receptor binding and antigenic diversity.", "mechanism": "Attachment to host cell receptors, influences tropism and immune response.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation affects antibody binding and neutralization.", "mechanism": "Targeted by monoclonal antibody Palivizumab to prevent infection.", "protein": "RSV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation required for fusion activity and immune evasion.", "mechanism": "Fusion protein mediates viral entry and syncytia formation in lung epithelial cells.", "protein": "HMPV F protein", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Croup", "glycan_involvement": "Sialic acid binding is glycan-dependent; glycosylation modulates receptor interaction.", "mechanism": "Binds sialic acids for cell entry; neuraminidase activity facilitates viral spread.", "protein": "HPIV HN protein", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Extensive glycosylation shields epitopes, modulates receptor binding and immune recognition.", "mechanism": "Spike mediates entry into airway cells, triggers immune response and lung injury.", "protein": "Coronavirus S protein", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation required for proper folding and receptor interaction.", "mechanism": "Facilitates viral entry and replication in lower respiratory tract.", "protein": "Coronavirus S protein", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Glycan recognition is essential for host cell attachment.", "mechanism": "Binds 9-O-acylated sialic acids, mediates entry and spread in airway epithelium.", "protein": "Coronavirus HE protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "medium", "disease": "Asthma exacerbation", "glycan_involvement": "Glycosylation may affect receptor binding and immune response.", "mechanism": "Capsid protein mediates cell entry, disrupts epithelial barrier, triggers inflammation.", "protein": "Rhinovirus VP1", "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "medium", "disease": "Persistent wheezing/asthma", "glycan_involvement": "Glycosylation drives antigenic variation and immune escape.", "mechanism": "Antigenic diversity and immune modulation linked to long-term airway disease.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC7149770" }, { "confidence": "high", "disease": "Respiratory disease", "glycan_involvement": "Highly glycosylated; glycosylation affects immune evasion and host cell binding.", "mechanism": "S protein mediates attachment and entry into respiratory epithelial cells, determining tissue tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "high", "disease": "Enteric disease (diarrhea)", "glycan_involvement": "Glycosylation modulates host range and immune response.", "mechanism": "S protein determines tropism for enteric epithelial cells, leading to diarrhea.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "high", "disease": "Severe acute respiratory syndrome (SARS)", "glycan_involvement": "Glycosylation influences receptor binding and immune escape.", "mechanism": "S protein variation enables cross-species transmission and severe lung disease.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "medium", "disease": "Kidney disease", "glycan_involvement": "Glycosylation affects tissue specificity.", "mechanism": "S protein determines tropism for kidney epithelial cells in IBV.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "medium", "disease": "Gonadal disease", "glycan_involvement": "Glycosylation modulates tissue tropism.", "mechanism": "S protein mediates infection of gonadal tissues in IBV.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "medium", "disease": "Central nervous system disease (demyelination)", "glycan_involvement": "Glycosylation may affect neurotropism.", "mechanism": "S protein determines CNS cell tropism in MHV, leading to demyelination.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "high", "disease": "Infectious bronchitis (IBV)", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "S1 subunit is major inducer of protective immunity; target of vaccines.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7149783" }, { "confidence": "medium", "disease": "Transmissible gastroenteritis (TGEV)", "glycan_involvement": "N- or O-linked glycosylation near N-terminus; type does not affect virus growth.", "mechanism": "M protein is essential for virion assembly and infectivity.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "low", "disease": "Porcine haemagglutinating encephalomyelitis", "glycan_involvement": "HE is a glycoprotein; glycosylation may modulate function.", "mechanism": "HE protein may affect tissue tropism and pathogenesis in CNS.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "medium", "disease": "Bovine enteritis", "glycan_involvement": "Glycosylation influences host specificity.", "mechanism": "S protein determines host range and enteric tropism in BCoV.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149783" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "N-glycosylation required for proper folding, immune evasion, and receptor binding.", "mechanism": "Mediates viral attachment and fusion via ACE2; critical for cell entry and tropism.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "N-glycosylation modulates receptor interaction and immune escape.", "mechanism": "Mediates viral attachment and fusion via DPP4; determines host cell tropism.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Gastroenteritis (torovirus)", "glycan_involvement": "Glycosylation enables sialic acid binding and esterase activity.", "mechanism": "Binds and cleaves sialic acid on host glycoproteins, facilitating mucosal penetration.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation of ectodomain affects assembly and immune recognition.", "mechanism": "Promotes virion assembly and membrane curvature; interacts with other structural proteins.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation may influence ion channel activity and immune modulation.", "mechanism": "Induces proinflammatory cytokines and forms ion channels (viroporin), contributing to pathogenesis.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Membrane association may involve glycosylation; not fully characterized.", "mechanism": "Interferes with cell signaling pathways and modulates virus release.", "protein": "Accessory protein 3a", "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Membrane association may involve glycosylation; not fully characterized.", "mechanism": "Antagonizes type I interferon signaling, delaying immune response.", "protein": "Accessory protein 6", "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "high", "disease": "Feline Infectious Peritonitis (FIP)", "glycan_involvement": "Glycosylation may affect tropism and immune evasion.", "mechanism": "Mutation in S protein changes tropism from enterocytes to macrophages, enabling systemic infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Infectious Bronchitis (IBV)", "glycan_involvement": "Glycosylation required for sialic acid binding.", "mechanism": "Facilitates binding to sialic acid on host cells, promoting infection.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "N-glycosylation modulates immune recognition and receptor binding.", "mechanism": "Mediates attachment and entry into respiratory epithelial cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149805" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects antigenicity and immune evasion.", "mechanism": "Surface glycoprotein mediating viral entry; target for neutralizing antibodies and vaccine design.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates enzymatic activity and immune recognition.", "mechanism": "Surface glycoprotein involved in viral release; target for antiviral drugs and vaccine design.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "high", "disease": "Human papillomavirus (HPV) infection/cervical cancer", "glycan_involvement": "Glycosylation influences immunogenicity and VLP assembly.", "mechanism": "Major capsid glycoprotein; basis for VLP vaccines (e.g., Gardasil, Cervarix).", "protein": "L1 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "medium", "disease": "Human papillomavirus (HPV) infection/cervical cancer", "glycan_involvement": "Glycosylation may affect epitope exposure.", "mechanism": "Minor capsid glycoprotein; potential vaccine target for broader protection.", "protein": "L2 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation of CD4 modulates HIV binding and immune function.", "mechanism": "CD4 glycoprotein is the primary receptor for HIV entry into T-helper cells.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7149942" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Altered O-glycosylation creates tumor-specific epitopes.", "mechanism": "Cell surface mucin glycoprotein; aberrant glycosylation in cancer; peptide vaccines under trial.", "protein": "MUC-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Tumor-associated glycoforms enhance immunogenicity.", "mechanism": "Overexpressed and aberrantly glycosylated in breast cancer; target for peptide vaccines.", "protein": "MUC-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Viral nucleocapsid glycoprotein; CTL epitopes used in peptide vaccine development.", "protein": "Core protein (Hepatitis C virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "medium", "disease": "Human papillomavirus (HPV) infection/cervical cancer", "glycan_involvement": "Potential glycosylation may modulate immune response.", "mechanism": "Oncoprotein; peptide epitopes induce strong cell-mediated immunity.", "protein": "E5 protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7149942" }, { "confidence": "high", "disease": "Multiple diseases (e.g., viral infections, cancer)", "glycan_involvement": "N-glycosylation essential for proper folding and peptide presentation.", "mechanism": "Present glycopeptide antigens to T-cells; critical for adaptive immunity and vaccine efficacy.", "protein": "Major Histocompatibility Complex (MHC) molecules", "relationship_type": "protective", "source_pmcid": "PMC7149942" }, { "confidence": "high", "disease": "Dengue fever (DF)", "glycan_involvement": "N-glycosylation of E is critical for receptor binding and infectivity.", "mechanism": "Mediates viral entry via receptor binding and membrane fusion.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Dengue hemorrhagic fever (DHF)", "glycan_involvement": "Glycosylation modulates antigenicity and immune recognition.", "mechanism": "E protein variability leads to serotype-specific immunity and ADE, contributing to severe disease.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Dengue fever (DF)", "glycan_involvement": "Glycosylation of prM/E affects viral maturation and secretion.", "mechanism": "Immature virions with prM/E are non-infectious; maturation (glycan-dependent) is required for infectivity.", "protein": "prM/E heterodimer", "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Dengue hemorrhagic fever (DHF)", "glycan_involvement": "NS1 is heavily glycosylated, affecting secretion and immune evasion.", "mechanism": "Secreted NS1 is detected in patient serum and correlates with disease severity.", "protein": "NS1 protein", "relationship_type": "biomarker", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Antibody-dependent enhancement (ADE)", "glycan_involvement": "Glycosylation influences epitope exposure and antibody binding.", "mechanism": "Cross-reactive antibodies to E protein facilitate ADE, increasing risk of severe disease.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Dengue fever (DF)", "glycan_involvement": "Interaction is glycan-dependent (mannose-rich N-glycans on E).", "mechanism": "DC-SIGN binds high-mannose glycans on E protein, mediating viral entry into dendritic cells.", "protein": "DC-SIGN", "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "medium", "disease": "Dengue fever (DF)", "glycan_involvement": "Requires N-glycosylation of E protein.", "mechanism": "Facilitates DENV entry into macrophages via recognition of glycosylated E protein.", "protein": "Mannose receptor", "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "medium", "disease": "Dengue hemorrhagic fever (DHF)", "glycan_involvement": "Interaction is glycan-dependent.", "mechanism": "CLEC5A binding to DENV glycoproteins triggers proinflammatory cytokine release, contributing to severe disease.", "protein": "CLEC5A", "protein_enriched": { "function": "Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity)", "gene_name": "CLEC5A", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9NY25" }, "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "medium", "disease": "Dengue fever (DF)", "glycan_involvement": "Binding depends on E protein glycosylation.", "mechanism": "Acts as an attachment factor for DENV via E protein glycan interactions.", "protein": "Heparan sulfate proteoglycan", "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "medium", "disease": "Dengue shock syndrome (DSS)", "glycan_involvement": "Glycosylation is required for NS1 secretion and pathogenic activity.", "mechanism": "Secreted NS1 disrupts endothelial barrier, contributing to vascular leakage.", "protein": "NS1 protein", "relationship_type": "causal", "source_pmcid": "PMC7149978" }, { "confidence": "high", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "N-glycosylation of gp116 is critical for viral replication and pathogenicity", "mechanism": "gp116 is a major envelope glycoprotein required for YHV virion infectivity and cell entry", "protein": "gp116", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "N-glycosylation of gp64 is required for efficient virus replication and disease", "mechanism": "gp64 is a major envelope glycoprotein forming virion spikes, essential for infection", "protein": "gp64", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Gill-Associated Virus Disease", "glycan_involvement": "N-glycosylation required for GAV replication and pathogenesis", "mechanism": "gp116 is essential for GAV virion infectivity and shrimp cell entry", "protein": "gp116", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Gill-Associated Virus Disease", "glycan_involvement": "N-glycosylation required for GAV replication and disease", "mechanism": "gp64 forms envelope spikes, mediates cell entry in GAV infection", "protein": "gp64", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "Blocking N-glycosylation impairs gp116 function and virus production", "mechanism": "Inhibition of N-glycosylation (e.g., tunicamycin) reduces YHV replication and shrimp mortality", "protein": "gp116", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "Blocking N-glycosylation impairs gp64 function and virus production", "mechanism": "Inhibition of N-glycosylation reduces YHV replication and disease severity", "protein": "gp64", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150020" }, { "confidence": "medium", "disease": "Fathead Minnow Nidovirus Disease", "glycan_involvement": "N-glycosylation inferred as important for function (by analogy to other nidoviruses)", "mechanism": "S glycoprotein forms envelope spikes, mediates host cell entry in fish nidovirus infection", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "medium", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "Glycosylation status may affect antigenicity", "mechanism": "gp116 is a major structural protein detected in diagnostic assays for YHV infection", "protein": "gp116", "relationship_type": "biomarker", "source_pmcid": "PMC7150020" }, { "confidence": "medium", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "Glycosylation status may affect antigenicity", "mechanism": "gp64 is a major structural protein detected in diagnostic assays for YHV infection", "protein": "gp64", "relationship_type": "biomarker", "source_pmcid": "PMC7150020" }, { "confidence": "medium", "disease": "Yellow Head Disease (YHD)", "glycan_involvement": "Deletion is N-terminal, glycosylation sites remain functional", "mechanism": "A 54 amino acid deletion in gp116 (YHV1b variant) does not significantly alter pathogenicity", "protein": "gp116", "relationship_type": "causal", "source_pmcid": "PMC7150020" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "IgG glycosylation may affect immune complex formation and clearance", "mechanism": "Increased CSF IgG due to intrathecal synthesis during CNS inflammation", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "high", "disease": "Other inflammatory CNS disorders", "glycan_involvement": "Glycosylation modulates IgG effector functions", "mechanism": "Elevated CSF IgG reflects intrathecal immune response", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Acute viral disease", "glycan_involvement": "IgM is highly glycosylated, affecting complement activation", "mechanism": "Early intrathecal IgM synthesis indicates acute immune response", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Chronic inflammatory CNS diseases", "glycan_involvement": "IgA glycosylation influences mucosal immunity and aggregation", "mechanism": "Intrathecal IgA production in chronic CNS inflammation", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Tuberculous meningitis", "glycan_involvement": "Plasma cell-derived immunoglobulins are glycosylated", "mechanism": "Presence of plasma cells in CSF indicates local antibody production", "protein": "Plasma cells (Ig-producing)", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Syphilis", "glycan_involvement": "Glycosylation of secreted Igs modulates immune response", "mechanism": "CSF plasma cells reflect CNS infection and antibody response", "protein": "Plasma cells (Ig-producing)", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 syndrome", "glycan_involvement": "Ig glycosylation may influence pathogenicity", "mechanism": "CSF plasma cells indicate immune-mediated demyelination", "protein": "Plasma cells (Ig-producing)", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "CSF leak (not directly mentioned but implied in clinical context)", "glycan_involvement": "Tau protein is a glycoprotein; glycosylation may affect detection", "mechanism": "Presence of tau protein distinguishes CSF from other fluids", "protein": "Tau protein (beta-2 transferrin)", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "medium", "disease": "Neoplasia (CNS)", "glycan_involvement": "Transferrin glycoforms are used to distinguish CSF origin", "mechanism": "Altered transferrin isoforms in CSF may indicate neoplastic processes", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "low", "disease": "Inflammatory CNS diseases", "glycan_involvement": "Highly glycosylated; glycan changes may modulate inflammation", "mechanism": "Increased CSF alpha-1 glycoprotein reflects inflammation", "protein": "Alpha-1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7150067" }, { "confidence": "high", "disease": "Cystic Fibrosis", "glycan_involvement": "Glycosylation affects CFTR folding and trafficking.", "mechanism": "Mutations in CFTR glycoprotein disrupt chloride transport, leading to thick mucus and disease.", "protein": "CFTR", "relationship_type": "causal", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "N-glycosylation required for LDLR function and cell surface expression.", "mechanism": "Mutations in LDLR glycoprotein impair LDL uptake, causing high cholesterol.", "protein": "LDLR", "protein_enriched": { "function": "Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must f", "gene_name": "LDLR", "glycan_count": 28, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G43417UB", "G57321FI", "G22768VO", "G11629QQ", "G22573RC", "G25451PN", "G43769HG", "G83229XP", "G84452RH", "G37881RL", "G00406II", "G00912UN", "G41071NU", "G45395BF", "G47012YE", "G70619PT", "G75983OB", "G96430BV", "G48414YA", "G49108TO", "G29068FM", "G31852PQ", "G45827ZM", "G47318KU", "G71838YU", "G74722FL", "G80111QD", "G81006GJ" ], "uniprot_id": "P01130" }, "relationship_type": "causal", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Familial Hypercholesterolemia", "glycan_involvement": "Glycosylation modulates APOB structure and LDL particle stability.", "mechanism": "APOB mutations reduce LDL binding to LDLR, increasing cholesterol.", "protein": "APOB", "relationship_type": "causal", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Multidrug Resistant Cancer", "glycan_involvement": "Glycosylation affects P-glycoprotein localization and activity.", "mechanism": "Overexpression leads to drug efflux and resistance.", "protein": "P-glycoprotein (MDR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150074" }, { "confidence": "medium", "disease": "Chronic Beryllium Disease", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "HLA-DPB1 Glu69 variant increases risk of immune-mediated lung disease.", "protein": "HLA-DPB1", "relationship_type": "causal/risk", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Sickle Cell Disease", "glycan_involvement": "Minor; glycosylation not central to pathogenesis.", "mechanism": "Mutation causes abnormal hemoglobin polymerization.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzyme activity and immune evasion.", "mechanism": "Neuraminidase glycoprotein is targeted by antiviral drugs.", "protein": "Neuraminidase (Influenza)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield protects virus from antibodies.", "mechanism": "gp120 mediates viral entry and is highly glycosylated to evade immunity.", "protein": "HIV gp120", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation required for secretion and immune recognition.", "mechanism": "HBsAg is used for diagnosis and is essential for viral infectivity.", "protein": "HBV surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation modulates immune evasion and receptor binding.", "mechanism": "E2 glycoprotein mediates viral entry and is a target for neutralizing antibodies.", "protein": "HCV E2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7150074" }, { "confidence": "high", "disease": "Respiratory disease", "glycan_involvement": "Glycosylation affects receptor binding and fusion activity.", "mechanism": "Mediates viral entry and fusion with respiratory epithelial cells via receptor binding.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "high", "disease": "Enteric disease", "glycan_involvement": "Glycosylation modulates tropism and infectivity.", "mechanism": "Determines tissue tropism for enteric epithelial cells; mutations alter tropism and virulence.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "Glycosylation may affect immune evasion and cell targeting.", "mechanism": "Mutations in S glycoprotein convert enteric FeCoV to systemic FIPV.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "medium", "disease": "Respiratory disease", "glycan_involvement": "Recognizes N-acetyl-9-O-acetylneuraminic acid or N-glycolylneuraminic acid.", "mechanism": "Binds sialic acid derivatives on respiratory cells, facilitating infection.", "protein": "HE glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "high", "disease": "Enteric disease", "glycan_involvement": "Glycosylation of APN is essential for virus binding.", "mechanism": "Acts as receptor for TGEV, FIPV, FeCoV, and HCoV-229E, enabling viral entry.", "protein": "Aminopeptidase N (APN)", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Serve as receptor for MHV, mediating hepatic infection.", "protein": "Murine biliary glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "medium", "disease": "Encephalomyelitis", "glycan_involvement": "Glycosylation may affect neuroinvasion.", "mechanism": "Mutations in S glycoprotein alter neurotropism and persistence in CNS.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "medium", "disease": "Nephritis", "glycan_involvement": "Glycosylation influences tropism.", "mechanism": "Tissue tropism determined by S glycoprotein sequence; IBV strains cause nephritis.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "high", "disease": "Colds (human)", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Mediates entry into human respiratory epithelial cells.", "protein": "S glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "medium", "disease": "Dilated myocardiopathy (rabbit)", "glycan_involvement": "Binds sialic acid derivatives on cardiac cells.", "mechanism": "Cardiotropic rabbit coronavirus uses HE for cell entry.", "protein": "HE glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150129" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation of CD4 affects HIV binding affinity.", "mechanism": "HIV binds CD4 glycoprotein for cell entry.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates CCR5 surface expression and HIV tropism.", "mechanism": "CCR5 acts as co-receptor for HIV entry.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "high", "disease": "Chronic hepatitis B", "glycan_involvement": "N-glycosylation required for proper folding and antigen presentation.", "mechanism": "Presentation of viral peptides to CD8 T cells for clearance.", "protein": "MHC class I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7150138" }, { "confidence": "medium", "disease": "Herpes simplex stromal keratitis", "glycan_involvement": "Glycosylation affects peptide loading and T cell activation.", "mechanism": "Presentation of HSV antigens to CD4 T cells drives immunopathology.", "protein": "MHC class II", "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "medium", "disease": "Chronic hepatitis C", "glycan_involvement": "Glycosylation may regulate PD-1 stability and signaling.", "mechanism": "PD-1 upregulation leads to T cell exhaustion.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150138" }, { "confidence": "medium", "disease": "Chronic hepatitis C", "glycan_involvement": "Glycosylation required for IL-10 secretion and activity.", "mechanism": "IL-10 suppresses antiviral T cell responses, promoting persistence.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "medium", "disease": "Vaccinia virus infection", "glycan_involvement": "Glycosylation stabilizes IL-18BP and enhances binding.", "mechanism": "Viral IL-18BP inhibits host IL-18, blunting immune response.", "protein": "IL-18-binding protein", "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "medium", "disease": "Cytomegalovirus persistence", "glycan_involvement": "Glycosylation affects receptor function and immune evasion.", "mechanism": "Viral US28 mimics chemokine receptor, modulating immune cell trafficking.", "protein": "US28", "protein_enriched": { "function": "", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QF73" }, "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation shields gp120 from neutralizing antibodies.", "mechanism": "gp120 mediates viral attachment to CD4 and CCR5.", "protein": "HIV gp120", "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "high", "disease": "Influenza infection", "glycan_involvement": "Glycosylation modulates receptor binding and antigenicity.", "mechanism": "Hemagglutinin binds sialylated glycoproteins on host cells for entry.", "protein": "Influenza hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7150138" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation of HN is essential for receptor binding and immune evasion.", "mechanism": "HN mediates viral attachment and entry into host cells, enabling infection.", "protein": "Hemagglutinin-neuraminidase (HN)", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "high", "disease": "Bronchiolitis and pneumonia (RSV)", "glycan_involvement": "Glycosylation modulates fusogenic activity and immune recognition.", "mechanism": "F protein mediates membrane fusion, facilitating viral entry and syncytium formation.", "protein": "Fusion protein (F)", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "high", "disease": "Ebola hemorrhagic fever", "glycan_involvement": "Heavily glycosylated mucin-like domain shields epitopes from immune detection.", "mechanism": "GP mediates viral attachment, entry, and immune evasion, leading to systemic infection.", "protein": "Glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Hantavirus pulmonary syndrome", "glycan_involvement": "Glycosylation is required for proper folding and function.", "mechanism": "Gn is involved in viral attachment and entry into endothelial cells.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Hantavirus pulmonary syndrome", "glycan_involvement": "Glycosylation affects fusion activity and immune evasion.", "mechanism": "Gc mediates membrane fusion and cell entry.", "protein": "Gc", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Hemorrhagic fever with renal syndrome (HFRS)", "glycan_involvement": "Glycosylation is important for receptor interaction.", "mechanism": "Gn facilitates viral entry into renal endothelial cells.", "protein": "Gn", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "high", "disease": "Lassa fever", "glycan_involvement": "Glycosylation is critical for processing, trafficking, and shielding from antibodies.", "mechanism": "GPC is cleaved into mature glycoproteins that mediate cell entry and immune evasion.", "protein": "Glycoprotein precursor (GPC)", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Lassa fever", "glycan_involvement": "Glycosylation shields epitopes and modulates infectivity.", "mechanism": "GP mediates viral entry into host cells.", "protein": "Glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Gastroenteritis (Rotavirus)", "glycan_involvement": "Glycosylation affects host cell binding and immune response.", "mechanism": "VP4 mediates attachment and penetration into intestinal epithelial cells.", "protein": "VP4 (spike protein)", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "medium", "disease": "Respiratory infection (Sendai virus)", "glycan_involvement": "Glycosylation is necessary for receptor binding and antigenicity.", "mechanism": "HN enables viral attachment and entry into respiratory epithelial cells.", "protein": "Hemagglutinin-neuraminidase (HN)", "relationship_type": "causal", "source_pmcid": "PMC7150163" }, { "confidence": "high", "disease": "Graft rejection", "glycan_involvement": "Glycosylation affects peptide binding and immune recognition.", "mechanism": "H2 glycoproteins present antigens and determine graft compatibility; mismatches cause rejection.", "protein": "H2 complex (MHC, H2)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "high", "disease": "Diabetes (Lepr db)", "glycan_involvement": "Glycosylation required for receptor function and trafficking.", "mechanism": "Lepr db mutation leads to defective glycoprotein receptor, causing obesity and diabetes.", "protein": "Leptin receptor (Lepr)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "high", "disease": "Cystic fibrosis", "glycan_involvement": "N-glycosylation affects CFTR folding and stability.", "mechanism": "CFTR glycoprotein mutations disrupt chloride transport, causing disease.", "protein": "Cystic fibrosis transmembrane conductance regulator (CFTR)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "high", "disease": "Albinism", "glycan_involvement": "Glycosylation required for enzyme stability and activity.", "mechanism": "Mutations in glycoprotein tyrosinase cause loss of melanin synthesis.", "protein": "Tyrosinase (Tyr)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "medium", "disease": "Lysosomal storage disease (beige)", "glycan_involvement": "Glycosylation important for lysosomal targeting.", "mechanism": "Lyst glycoprotein mutation leads to lysosomal trafficking defects.", "protein": "Lyst (beige gene product)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "medium", "disease": "Demyelinating disease", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Altered MBP glycoprotein expression linked to myelin disorders.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "biomarker", "source_pmcid": "PMC7150197" }, { "confidence": "medium", "disease": "Cancer (mammary tumor)", "glycan_involvement": "Glycosylation affects receptor dimerization and signaling.", "mechanism": "Overexpression of Erb2 glycoprotein drives tumorigenesis.", "protein": "Erb2 (HER2/neu)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "medium", "disease": "Immune response to infection", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Complement glycoproteins mediate pathogen clearance.", "protein": "Complement proteins", "relationship_type": "protective", "source_pmcid": "PMC7150197" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "N-glycosylation modulates immune tolerance.", "mechanism": "Altered glycosylation of MHC I affects self-antigen presentation.", "protein": "Major histocompatibility complex class I (H2-K, H2-D, H2-L)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "high", "disease": "Immune response to infection", "glycan_involvement": "Glycosylation affects antigen binding and presentation.", "mechanism": "MHC II glycoproteins present antigens to T cells, critical for immunity.", "protein": "Major histocompatibility complex class II (I-A, I-E)", "relationship_type": "causal", "source_pmcid": "PMC7150197" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield modulates immune recognition and antibody access.", "mechanism": "Target of broadly neutralizing antibodies; vaccine efforts focus on eliciting antibodies to glycan-dependent epitopes.", "protein": "HIV Envelope Glycoprotein (gp120/gp41)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150210" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects antigenicity and immune evasion.", "mechanism": "Major target of neutralizing antibodies; vaccines aim to induce antibodies to HA head and stem regions.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150210" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus (RSV) Disease", "glycan_involvement": "Glycosylation influences epitope exposure and immunogenicity.", "mechanism": "Target of neutralizing antibodies (e.g., palivizumab); vaccines focus on prefusion F conformation.", "protein": "RSV Fusion Glycoprotein (F)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150210" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity.", "mechanism": "HBsAg-based VLP vaccines induce protective antibody responses.", "protein": "Hepatitis B Surface Antigen (HBsAg)", "relationship_type": "protective", "source_pmcid": "PMC7150210" }, { "confidence": "high", "disease": "Human Papillomavirus (HPV)-associated diseases", "glycan_involvement": "VLP assembly and immunogenicity depend on proper glycosylation.", "mechanism": "L1 VLPs induce neutralizing antibodies, preventing infection and associated cancers.", "protein": "HPV L1 Protein (VLP component)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7150210" }, { "confidence": "medium", "disease": "Measles", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "Target of neutralizing antibodies; vaccine induces lifelong immunity.", "protein": "Measles Virus Hemagglutinin", "protein_enriched": { "function": "Attaches the virus to the human SLAMF1/CD150 receptor for entry into host dendritic cells, macrophages, activated memory T cells and naive or memory B cells, thereby explaining the long immunosuppress", "gene_name": "H", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P08362" }, "relationship_type": "protective", "source_pmcid": "PMC7150210" }, { "confidence": "medium", "disease": "Mumps", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Target of neutralizing antibodies; vaccine confers protection.", "protein": "Mumps Virus Hemagglutinin-Neuraminidase", "relationship_type": "protective", "source_pmcid": "PMC7150210" }, { "confidence": "medium", "disease": "Rubella", "glycan_involvement": "Glycosylation required for proper folding and antigenicity.", "mechanism": "Target of neutralizing antibodies; vaccine induces immunity.", "protein": "Rubella Virus E1 Glycoprotein", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08562" }, "relationship_type": "protective", "source_pmcid": "PMC7150210" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Glycosylation affects epitope presentation and immune response.", "mechanism": "Target of neutralizing antibodies; vaccine candidates focus on E protein.", "protein": "Dengue Virus Envelope Glycoprotein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "pol", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "Q6YMS4" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150210" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) Disease", "glycan_involvement": "Glycosylation modulates immunogenicity.", "mechanism": "Target of neutralizing antibodies; vaccine candidates include gB.", "protein": "CMV Glycoprotein B (gB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150210" }, { "confidence": "high", "disease": "Classical swine fever", "glycan_involvement": "Glycosylation of E2 is important for antigenicity and immunogenicity.", "mechanism": "E2 glycoprotein is used as a subunit vaccine antigen to induce protective immunity.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects HA folding and immunogenicity; insect cell glycosylation differs from mammalian.", "mechanism": "HA is the main antigen in recombinant influenza vaccines (e.g., Flublok) to elicit protective antibodies.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "high", "disease": "Cervical cancer (HPV infection)", "glycan_involvement": "Glycosylation may affect VLP assembly and immunogenicity.", "mechanism": "L1 forms VLPs used in vaccines (e.g., Cervarix) to induce neutralizing antibodies against HPV.", "protein": "HPV L1 protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "N/A (vaccine vector platform)", "glycan_involvement": "GP64 is a phosphoglycoprotein; glycosylation is required for proper folding and function.", "mechanism": "GP64 is used for surface display of antigens on baculovirus vectors to enhance immune response.", "protein": "GP64", "protein_enriched": { "function": "", "gene_name": "gag", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QFQ2" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "N/A (gene therapy vector)", "glycan_involvement": "Glycosylation supports membrane fusion activity.", "mechanism": "VSV-G is displayed on baculovirus to improve transduction efficiency in vertebrate cells.", "protein": "VSV-G protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Gp120 is heavily glycosylated; glycan shield affects immunogenicity.", "mechanism": "Gp120 is used in VLPs to induce immune responses against HIV.", "protein": "Gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "Glycosylation is important for proper folding and antigenicity.", "mechanism": "gE is used in VLPs to induce protective immunity.", "protein": "gE (glycoprotein E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "Ebola virus disease", "glycan_involvement": "Glycosylation is critical for antigenicity and immunogenicity.", "mechanism": "Gn and Gc are used in VLPs to induce immune responses against Ebola and Marburg viruses.", "protein": "Gn and Gc", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "Glycosylation may affect antigen processing and presentation.", "mechanism": "PAP is used as an antigen in immunotherapy (Provenge) to stimulate anti-tumor immunity.", "protein": "Prostatic acid phosphatase (PAP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "medium", "disease": "Familial lipoprotein lipase deficiency", "glycan_involvement": "Glycosylation is required for enzyme stability and activity.", "mechanism": "Gene therapy delivers functional lipoprotein lipase to compensate for deficiency.", "protein": "Lipoprotein lipase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150248" }, { "confidence": "high", "disease": "Acquired Immunodeficiency Syndrome (AIDS)", "glycan_involvement": "Heavy N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates HIV-1 entry via CD4 and coreceptors, initiating infection.", "protein": "HIV-1 Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC7150357" }, { "confidence": "high", "disease": "Chronic Hepatitis C", "glycan_involvement": "N-glycosylation modulates E2 antigenicity and receptor binding.", "mechanism": "E2 binds CD81 on hepatocytes, facilitating viral entry and persistence.", "protein": "HCV Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC7150357" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "N-glycosylation affects secretion and immunogenicity.", "mechanism": "HBsAg presence in serum indicates active HBV infection.", "protein": "HBV Surface Antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC7150357" }, { "confidence": "high", "disease": "Chronic Hepatitis B", "glycan_involvement": "Glycosylation influences secretion and immune tolerance.", "mechanism": "HBeAg in serum marks viral replication and infectivity.", "protein": "HBV e Antigen (HBeAg)", "protein_enriched": { "function": "The phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active transport system, catalyzes the phosphorylation of incoming sugar substrates concomitantly wi", "gene_name": "manX", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P69798" }, "relationship_type": "biomarker", "source_pmcid": "PMC7150357" }, { "confidence": "medium", "disease": "Acute Hepatitis C", "glycan_involvement": "Limited glycosylation; antigenicity affected by glycan status.", "mechanism": "Core antigen detection indicates active HCV replication.", "protein": "HCV Core Antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7150357" }, { "confidence": "high", "disease": "HIV-1 Infection", "glycan_involvement": "N-glycosylation modulates fusion and immune evasion.", "mechanism": "gp41 mediates membrane fusion; target for fusion inhibitors.", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150357" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "N-glycosylation affects folding and immune recognition.", "mechanism": "E1 forms heterodimer with E2, essential for viral entry.", "protein": "HCV Envelope Glycoprotein E1", "relationship_type": "causal", "source_pmcid": "PMC7150357" }, { "confidence": "medium", "disease": "Hepatocellular Carcinoma", "glycan_involvement": "Altered glycosylation promotes immune escape and carcinogenesis.", "mechanism": "PreS mutations/glycosylation linked to oncogenic transformation.", "protein": "HBV PreS Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7150357" }, { "confidence": "low", "disease": "HIV-1 Infection", "glycan_involvement": "Not glycosylated; included for completeness.", "mechanism": "Gag gene sequence diversity used for viral subtyping and monitoring.", "protein": "HIV-1 Gag Protein", "relationship_type": "biomarker", "source_pmcid": "PMC7150357" }, { "confidence": "medium", "disease": "Chronic Hepatitis C", "glycan_involvement": "No direct glycosylation; functional region linked to therapy response.", "mechanism": "NS5A modulates interferon response; target for DAAs.", "protein": "HCV NS5A Protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7150357" }, { "confidence": "high", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Not specified", "mechanism": "SNPs and mutations in IFIH1/MDA5 cause constitutive activation, leading to aberrant type I IFN production and autoimmunity.", "protein": "MDA5 (IFIH1)", "relationship_type": "causal", "source_pmcid": "PMC7151769" }, { "confidence": "high", "disease": "Aicardi\u2013Goutieres syndrome (AGS)", "glycan_involvement": "Not specified", "mechanism": "Dominant gain-of-function mutations in IFIH1/MDA5 lead to constitutive IFN production, driving AGS.", "protein": "MDA5 (IFIH1)", "relationship_type": "causal", "source_pmcid": "PMC7151769" }, { "confidence": "high", "disease": "Singleton\u2013Merten syndrome (SMS)", "glycan_involvement": "Not specified", "mechanism": "Missense mutations (e.g., R822G) in IFIH1/MDA5 confer constitutive activity, causing SMS.", "protein": "MDA5 (IFIH1)", "relationship_type": "causal", "source_pmcid": "PMC7151769" }, { "confidence": "high", "disease": "Singleton\u2013Merten syndrome (SMS)", "glycan_involvement": "Not specified", "mechanism": "Missense mutations (e.g., E373A, C268F) in DDX58/RIG-I lead to constitutive IFN production and SMS.", "protein": "RIG-I (DDX58)", "protein_enriched": { "function": "Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:1", "gene_name": "RIGI", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G70994MS" ], "uniprot_id": "O95786" }, "relationship_type": "causal", "source_pmcid": "PMC7151769" }, { "confidence": "medium", "disease": "Type 1 diabetes (T1D)", "glycan_involvement": "Not specified", "mechanism": "Loss-of-function variants in IFIH1/MDA5 reduce risk of T1D by attenuating antiviral innate immune responses.", "protein": "MDA5 (IFIH1)", "relationship_type": "protective", "source_pmcid": "PMC7151769" }, { "confidence": "medium", "disease": "Psoriasis", "glycan_involvement": "Not specified", "mechanism": "GWAS links IFIH1 SNPs to increased risk of psoriasis.", "protein": "MDA5 (IFIH1)", "relationship_type": "risk", "source_pmcid": "PMC7151769" }, { "confidence": "medium", "disease": "Selective IgA deficiency", "glycan_involvement": "Not specified", "mechanism": "GWAS links IFIH1 SNPs to increased risk of selective IgA deficiency.", "protein": "MDA5 (IFIH1)", "relationship_type": "risk", "source_pmcid": "PMC7151769" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Not specified", "mechanism": "GWAS links IFIH1 SNPs to increased risk of dilated cardiomyopathy.", "protein": "MDA5 (IFIH1)", "relationship_type": "risk", "source_pmcid": "PMC7151769" }, { "confidence": "medium", "disease": "Clinically amyopathic dermatomyositis", "glycan_involvement": "Not specified", "mechanism": "Autoantibodies to MDA5 are found in a subset of patients.", "protein": "MDA5 (IFIH1)", "relationship_type": "biomarker", "source_pmcid": "PMC7151769" }, { "confidence": "high", "disease": "Viral infections", "glycan_involvement": "Viral glycoprotein mediates immune evasion via protein-protein interaction.", "mechanism": "Glycoprotein G binds RIG-I, sequestering it and preventing antiviral signaling.", "protein": "G (human metapneumovirus)", "relationship_type": "causal (immune evasion)", "source_pmcid": "PMC7151769" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "CEA is a heavily glycosylated cell surface protein; glycosylation is essential for its tumor-specific expression.", "mechanism": "Surface display of anti-CEA antibody fragments on Salmonella improves targeting to tumors overexpressing CEA.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "high", "disease": "Cancer (various types)", "glycan_involvement": "NY-ESO-1 is glycosylated; glycosylation may affect antigenicity.", "mechanism": "Surface display of NY-ESO-1 epitopes on bacterial fimbrial proteins induces robust T-cell responses against tumors.", "protein": "NY-ESO-1", "protein_enriched": { "function": "Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD)", "gene_name": "FAM8A1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9UBU6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "high", "disease": "Cervical cancer", "glycan_involvement": "E7 glycosylation may influence immune recognition.", "mechanism": "Surface expression of E7 on lactic acid bacteria generates effective mucosal vaccines against HPV-induced tumors.", "protein": "E7 oncoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Glycosylation is characteristic of oncofetal proteins and may affect immunogenicity.", "mechanism": "Surface display on lactic acid bacteria induces immune responses against tumors expressing this antigen.", "protein": "37 kDa oncofetoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "medium", "disease": "Cancer (various types)", "glycan_involvement": "Fimbrial glycosylation can modulate immune responses.", "mechanism": "Insertion of tumor epitopes into fimbrial proteins enables vaccine design for cancer immunotherapy.", "protein": "Fimbrial proteins (engineered)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "high", "disease": "Infectious diseases (bacterial/viral)", "glycan_involvement": "S-layer glycosylation is crucial for antigen presentation and stability.", "mechanism": "Surface display of antigens on glycosylated S-layer proteins enables whole-cell vaccine development.", "protein": "S-layer proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "high", "disease": "Streptococcus pneumoniae infection", "glycan_involvement": "Capsular polysaccharide glycosylation is essential for immunogenicity.", "mechanism": "Glycoengineering of capsular polysaccharide-protein conjugates on bacteria enables vaccine development.", "protein": "Capsular polysaccharide-linked proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "medium", "disease": "Anthrax", "glycan_involvement": "Glycosylation of sortase substrates affects antigen stability and immune response.", "mechanism": "Sortase-mediated display of anthrax antigens on bacterial surface for vaccine development.", "protein": "Sortase substrate proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "medium", "disease": "Infectious diseases (bacterial/viral)", "glycan_involvement": "OmpA glycosylation may influence antigen display and immunogenicity.", "mechanism": "Fusion of antigens to OmpA on bacterial ghosts for vaccine delivery.", "protein": "OmpA", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "medium", "disease": "Rotavirus infection", "glycan_involvement": "ClyA glycosylation may affect vesicle formation and antigen presentation.", "mechanism": "Fusion of antigens to ClyA on OMVs for mucosal vaccine development.", "protein": "ClyA", "protein_enriched": { "function": "This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly", "gene_name": "rplM", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0AA10" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152005" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation of spike protein is essential for infectivity and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry into host respiratory epithelial cells.", "protein": "Infectious Bronchitis Virus Spike Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7152007" }, { "confidence": "high", "disease": "Marek's Disease", "glycan_involvement": "Glycosylation modulates immune recognition and cell tropism.", "mechanism": "Envelope glycoproteins facilitate viral entry and tumorigenesis in lymphoid tissues.", "protein": "Marek's Disease Virus Envelope Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7152007" }, { "confidence": "high", "disease": "Avian Leukosis", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Envelope glycoprotein mediates host cell infection and oncogenesis.", "protein": "Avian Leukosis Virus Envelope Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7152007" }, { "confidence": "medium", "disease": "Blackhead (Histomoniasis)", "glycan_involvement": "Glycosylation may contribute to immune evasion.", "mechanism": "Surface glycoproteins mediate host cell attachment and immune modulation.", "protein": "Histomonas meleagridis Surface Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7152007" }, { "confidence": "medium", "disease": "Coccidiosis", "glycan_involvement": "Glycosylation is critical for parasite infectivity and immune evasion.", "mechanism": "Surface glycoproteins are involved in host cell invasion and pathogenicity.", "protein": "Coccidia Surface Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7152007" }, { "confidence": "high", "disease": "Acute diarrhea", "glycan_involvement": "NSP4 is a glycoprotein; glycosylation is essential for its enterotoxin activity.", "mechanism": "NSP4 acts as a viral enterotoxin causing secretory diarrhea in rotavirus infection.", "protein": "NSP4", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11194" }, "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Typhoid fever", "glycan_involvement": "Vi antigen is a polysaccharide capsule with glycosylation features.", "mechanism": "Vi capsular antigen is used for serotyping Salmonella Typhi, the agent of typhoid fever.", "protein": "Vi antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Hemolytic\u2013uremic syndrome", "glycan_involvement": "Shiga toxin binds to glycosylated Gb3 receptors on host cells.", "mechanism": "Shiga toxin produced by STEC causes endothelial damage leading to HUS.", "protein": "Shiga toxin", "protein_enriched": { "function": "The B subunit is responsible for the binding of the holotoxin to specific receptors on the target cell surface, such as globotriaosylceramide (Gb3) in human intestinal microvilli", "gene_name": "stxB2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09386" }, "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Cholera", "glycan_involvement": "Cholera toxin binds to GM1 ganglioside (glycosylated receptor) on enterocytes.", "mechanism": "Cholera toxin induces massive water secretion in the gut.", "protein": "Cholera toxin", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Pseudomembranous colitis", "glycan_involvement": "Toxin A is glycosylated; glycosylation affects its cytotoxicity.", "mechanism": "Toxin A from C. difficile causes inflammatory lesions in the colon.", "protein": "Toxin A", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Pseudomembranous colitis", "glycan_involvement": "Toxin B is glycosylated; glycosylation modulates activity.", "mechanism": "Toxin B from C. difficile is cytotoxic and causes colonic inflammation.", "protein": "Toxin B", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Guillain\u2013Barr\u00e9 syndrome", "glycan_involvement": "Molecular mimicry via glycan structures induces cross-reactive antibodies.", "mechanism": "Campylobacter jejuni LPS mimics host gangliosides, triggering autoimmunity.", "protein": "Ganglioside-like LPS motifs", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "medium", "disease": "Acute diarrhea", "glycan_involvement": "Enterotoxin is glycosylated, affecting its function.", "mechanism": "Yersinia enterocolitica enterotoxin induces diarrhea.", "protein": "Enterotoxin (Yersinia)", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Acute diarrhea", "glycan_involvement": "Toxin binds to glycosylated GM1 ganglioside on enterocytes.", "mechanism": "ETEC heat-labile toxin stimulates cAMP, causing watery diarrhea.", "protein": "Heat-labile enterotoxin (ETEC)", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "medium", "disease": "Acute diarrhea", "glycan_involvement": "Toxin interacts with glycosylated receptors.", "mechanism": "ETEC heat-stable toxin stimulates cGMP, causing diarrhea.", "protein": "Heat-stable enterotoxin (ETEC)", "relationship_type": "causal", "source_pmcid": "PMC7152011" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Albumin is a glycoprotein; glycosylation may affect receptor binding and tumor accumulation.", "mechanism": "Albumin-bound paclitaxel (Abraxane) targets tumors via gp60 and SPARC-mediated accumulation.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "gp60 is a glycoprotein; glycosylation may regulate ligand binding.", "mechanism": "gp60 mediates albumin transcytosis, enhancing tumor delivery of albumin-bound drugs.", "protein": "gp60 (albondin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "SPARC is a secreted glycoprotein; glycosylation may modulate its interaction with albumin.", "mechanism": "SPARC binds albumin, increasing tumor accumulation of albumin-bound drugs.", "protein": "SPARC", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "HER-2 is a glycoprotein; glycosylation affects antibody binding and receptor function.", "mechanism": "HER-2 targeted nanoparticles deliver drugs specifically to HER-2 positive cancer cells.", "protein": "HER-2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "high", "disease": "Brain cancer", "glycan_involvement": "TfR is a glycoprotein; glycosylation influences ligand recognition and endocytosis.", "mechanism": "TfR-targeted nanoparticles cross the blood-brain barrier and deliver drugs to brain tumors.", "protein": "Transferrin receptor (TfR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Folate receptor is a glycoprotein; glycosylation may affect ligand binding.", "mechanism": "Folate-conjugated nanoparticles target folate receptor-overexpressing ovarian cancer cells.", "protein": "Folate receptor", "protein_enriched": { "function": "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, P", "gene_name": "FOLR1", "glycan_count": 68, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G14972EH", "G16125XL", "G23294PN", "G25451PN", "G27058EU", "G28622IK", "G34989PA", "G39471UU", "G39619TI", "G40926MX", "G41071NU", "G43223CG", "G45395BF", "G47012YE", "G48414YA", "G59536GA", "G60177UT", "G62765YT", "G65184UU", "G66088HZ", "G66163OV", "G68490OW", "G70101JE", "G71051TA", "G75983OB", "G79666IR", "G80075MS", "G80920RR", "G82463GQ", "G83460ZZ", "G83646BJ", "G84452RH", "G85282JO", "G86795LJ", "G86880BF", "G87661QW", "G90382BL", "G92135MA", "G95133RI", "G98611JV", "G99668VU", "G92062TF", "G04657PL", "G05049YU", "G07755XJ", "G10819WX", "G11870QZ", "G13131HA", "G15169WU", "G15664MX", "G20210JR", "G23719VF", "G23984SE", "G31852PQ", "G36379GD", "G42124LM", "G45504EY", "G62894KT", "G70619PT", "G77547TA", "G84225JN", "G90659AW", "G95177YH", "G49108TO" ], "uniprot_id": "P15328" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "uPAR is a glycoprotein; glycosylation may modulate receptor-ligand interactions.", "mechanism": "uPAR-targeted nanoparticles deliver drugs to invasive breast cancer cells.", "protein": "Urokinase plasminogen activator receptor (uPAR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "medium", "disease": "Breast cancer", "glycan_involvement": "Integrins are glycoproteins; glycosylation affects cell adhesion and targeting.", "mechanism": "RGD peptide-modified nanoparticles target integrin \u03b15\u03b23 on tumor vasculature.", "protein": "Integrin \u03b15\u03b23", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "low", "disease": "Lung cancer", "glycan_involvement": "Sigma receptor is a glycoprotein; glycosylation may influence ligand binding.", "mechanism": "Anisamide-modified nanoparticles target sigma receptors on lung cancer cells.", "protein": "Sigma receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "low", "disease": "Ulcerative colitis", "glycan_involvement": "Cyclophilin is a glycoprotein; glycosylation may affect stability and immune recognition.", "mechanism": "Cyclosporine A delivered via nanoparticles targets immune cells in colon inflammation.", "protein": "Cyclosporine A target (cyclophilin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152047" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "N-glycosylation critical for protein folding and function; glycan shield affects immune recognition.", "mechanism": "Mediates viral entry and syncytium formation in airway epithelial cells, leading to infection and airway obstruction.", "protein": "RSV F protein", "relationship_type": "causal", "source_pmcid": "PMC7152174" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Heavily O-glycosylated; glycosylation modulates immune evasion and host cell binding.", "mechanism": "Mediates viral attachment to host cells, facilitating infection.", "protein": "RSV G protein", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P13842" }, "relationship_type": "causal", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "N-glycosylation affects oligomerization and pathogen binding.", "mechanism": "Polymorphisms associated with increased risk of severe disease and intensive care admission.", "protein": "Surfactant Protein A", "relationship_type": "biomarker", "source_pmcid": "PMC7152174" }, { "confidence": "high", "disease": "RSV Infection", "glycan_involvement": "IgG1 Fc N-glycosylation modulates effector function and half-life.", "mechanism": "Monoclonal antibody binds RSV F protein, neutralizing virus and preventing severe disease.", "protein": "Palivizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "RSV Infection", "glycan_involvement": "IgG N-glycosylation influences Fc receptor binding and immune modulation.", "mechanism": "Provides passive immunity, reducing RSV severity in high-risk infants.", "protein": "IVIG", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation may affect secretion/stability (not detailed in article).", "mechanism": "Elevated in secretions of infants hospitalized with RSV bronchiolitis; associated with disease severity.", "protein": "Interleukin-33", "protein_enriched": { "function": "Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016, PubMed:19841166). Involved in the ma", "gene_name": "IL33", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O95760" }, "relationship_type": "biomarker", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation may affect receptor binding (not detailed in article).", "mechanism": "Increased in secretions during severe RSV bronchiolitis.", "protein": "Interleukin-13", "relationship_type": "biomarker", "source_pmcid": "PMC7152174" }, { "confidence": "low", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation status not specified; may affect stability.", "mechanism": "Increased serum levels associated with more severe disease.", "protein": "Cathelicidin", "relationship_type": "biomarker", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Glycosylation may modulate immune response and long-term sequelae.", "mechanism": "Severe RSV bronchiolitis in infancy increases risk of asthma development later in childhood.", "protein": "RSV F protein", "relationship_type": "causal", "source_pmcid": "PMC7152174" }, { "confidence": "medium", "disease": "Bronchopulmonary Dysplasia", "glycan_involvement": "N-glycosylation affects function in lung immunity.", "mechanism": "Polymorphisms linked to increased risk of severe RSV disease in infants with BPD.", "protein": "Surfactant Protein A", "relationship_type": "biomarker", "source_pmcid": "PMC7152174" }, { "confidence": "high", "disease": "Lymphoma", "glycan_involvement": "Glycosylation of gp70 is essential for receptor binding and immune evasion.", "mechanism": "gp70 mediates viral entry and cell tropism, enabling FeLV infection and insertional mutagenesis leading to lymphoma.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "high", "disease": "Leukemia", "glycan_involvement": "Glycosylation modulates receptor interaction and immune recognition.", "mechanism": "gp70 facilitates FeLV infection of hematopoietic cells, leading to leukemogenesis via insertional mutagenesis.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "high", "disease": "Opportunistic infections", "glycan_involvement": "Glycosylation may affect immunosuppressive activity and stability.", "mechanism": "p15E inhibits T and B cell function, impairing immune responses and predisposing to infections.", "protein": "p15E", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "high", "disease": "Pure red cell aplasia", "glycan_involvement": "Glycosylation affects receptor specificity and pathogenicity.", "mechanism": "Mutations in SU (env) generate FeLV-C, which binds FLVCR (heme exporter), blocking heme export and causing erythroid precursor death.", "protein": "FeLV SU (env)", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "medium", "disease": "Aplastic anemia", "glycan_involvement": "Glycosylation required for efficient infection of target cells.", "mechanism": "gp70-mediated infection of bone marrow precursors leads to marrow failure.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "medium", "disease": "Immune-mediated hemolytic anemia (IMHA)", "glycan_involvement": "Glycosylation may modulate immunosuppressive properties.", "mechanism": "p15E-induced immunomodulation may trigger autoimmunity against erythrocytes.", "protein": "p15E", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "medium", "disease": "Neurologic disease", "glycan_involvement": "Glycosylation may influence neurotropism.", "mechanism": "gp70 (envelope protein) may be neurotoxic and is detected in CNS cells in affected cats.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "high", "disease": "Fibrosarcoma (FeSV-associated)", "glycan_involvement": "Glycosylation of gp70 is necessary for FeSV infectivity.", "mechanism": "gp70 is required for FeSV replication; FeSV arises from recombination with FeLV-A env gene.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "Glycosylation affects antigenicity and immune complex formation.", "mechanism": "gp70 antigen-antibody complexes may deposit in glomeruli, causing immune-mediated nephritis.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "medium", "disease": "Reproductive failure", "glycan_involvement": "Glycosylation required for placental cell infection.", "mechanism": "gp70-mediated infection of placenta/fetus leads to fetal loss.", "protein": "gp70", "relationship_type": "causal", "source_pmcid": "PMC7152252" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG may affect antigenicity and immune recognition.", "mechanism": "MOG acts as an autoantigen; immune response against MOG contributes to demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal/autoantigen", "source_pmcid": "PMC7152275" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Viral glycoproteins mediate cell entry and immune evasion.", "mechanism": "HHV-6 infects oligodendrocytes; viral glycoproteins may trigger immune response and demyelination.", "protein": "HHV-6 Envelope Glycoproteins", "relationship_type": "causal/trigger", "source_pmcid": "PMC7152275" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "ICAM-1 is a glycoprotein; glycosylation affects its function and interactions.", "mechanism": "Elevated soluble ICAM-1 in MS sera; involved in leukocyte adhesion and CNS infiltration.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC7152275" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "VCAM-1 glycosylation modulates adhesion properties.", "mechanism": "Increased soluble VCAM-1 in CSF of MS patients; facilitates immune cell migration into CNS.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC7152275" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "E-selectin is a glycoprotein; glycosylation is essential for ligand binding.", "mechanism": "Elevated in MS sera and CSF; mediates leukocyte rolling and adhesion.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC7152275" }, { "confidence": "medium", "disease": "Autoimmune reactions (post-HCMV infection)", "glycan_involvement": "CD13 is a glycoprotein; glycosylation may affect immunogenicity.", "mechanism": "CD13 incorporated into HCMV envelope; anti-CD13 antibodies cross-react with host tissues.", "protein": "CD13 (Aminopeptidase N)", "relationship_type": "causal/trigger", "source_pmcid": "PMC7152275" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Potential glycosylation may influence antigenicity.", "mechanism": "T-cell cross-reactivity between HHV-6 U24 and MBP promotes autoimmunity.", "protein": "HHV-6 U24", "relationship_type": "causal/molecular mimicry", "source_pmcid": "PMC7152275" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "101K is a viral glycoprotein; glycosylation may affect immune recognition.", "mechanism": "Reduced T-cell response to 101K in MS; increased IgM response suggests altered immunity.", "protein": "HHV-6 101K", "relationship_type": "biomarker/immune response", "source_pmcid": "PMC7152275" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MBP is not glycosylated; no direct glycan involvement.", "mechanism": "MBP-specific T cells mediate CNS demyelination.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "autoantigen", "source_pmcid": "PMC7152275" }, { "confidence": "medium", "disease": "Demyelinating Encephalomyelitis", "glycan_involvement": "Envelope glycoproteins mediate neurotropism and immune evasion.", "mechanism": "HHV-6 infection associated with demyelinating CNS diseases.", "protein": "HHV-6 Envelope Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7152275" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation of HA modulates receptor binding and immune evasion.", "mechanism": "Mediates viral attachment to sialic acid on host cells, enabling entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzyme activity and antigenicity.", "mechanism": "Cleaves sialic acid to release progeny virions; targeted by antivirals.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes from immune recognition.", "mechanism": "Binds CD4 and chemokine receptors to mediate viral entry.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates fusion activity and immune evasion.", "mechanism": "Mediates membrane fusion after gp120 binding; target of fusion inhibitors.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosylation required for proper folding and receptor interaction.", "mechanism": "Mediates HSV entry by binding to host receptors (HVEM, nectins).", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycans shield E2 from neutralizing antibodies.", "mechanism": "Mediates HCV entry by binding to CD81 and other receptors.", "protein": "Envelope glycoprotein (E2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "COVID-19/SARS", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates coronavirus entry via ACE2 binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "medium", "disease": "Epstein-Barr virus infection", "glycan_involvement": "Glycosylation affects receptor binding and immune recognition.", "mechanism": "Mediates EBV entry by binding MHC class II on B cells.", "protein": "gp42", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "medium", "disease": "Herpes simplex virus infection", "glycan_involvement": "N-glycans required for proper folding and function.", "mechanism": "Essential for HSV membrane fusion and entry.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation of VP4 modulates host range and infectivity.", "mechanism": "Mediates rotavirus attachment to sialic acid-containing glycans on enterocytes.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152303" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus Infection (FIV)", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield epitopes and modulate immune evasion", "mechanism": "gp120 mediates viral entry by binding to CD134 and CXCR4 on host cells", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus Infection (FIV)", "glycan_involvement": "gp41 is glycosylated, affecting fusion efficiency and immune recognition", "mechanism": "gp41 facilitates fusion of viral and host cell membranes", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Feline Immunodeficiency Virus Infection (FIV)", "glycan_involvement": "Glycosylation of CD134 may influence viral binding affinity", "mechanism": "CD134 is the primary receptor for FIV entry into CD4+ T cells", "protein": "CD134", "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Feline Immunodeficiency Virus Infection (FIV)", "glycan_involvement": "Glycosylation status may modulate receptor function and viral tropism", "mechanism": "CXCR4 acts as a co-receptor for FIV entry", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Opportunistic infections", "glycan_involvement": "MHC II is glycosylated; changes may affect immune recognition", "mechanism": "Altered MHC II expression on lymphocytes impairs antigen presentation, contributing to immunosuppression", "protein": "MHC II", "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Hyperglobulinemia in FIV", "glycan_involvement": "IgG glycosylation may modulate immune complex formation and clearance", "mechanism": "B cell hyperactivation leads to increased IgG, resulting in hyperglobulinemia", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Lymphoma", "glycan_involvement": "Glycosylation of gp120 may affect immune evasion and chronicity", "mechanism": "Viral integration and chronic immune activation by gp120 contribute to lymphomagenesis", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Lymphoplasmacytic stomatitis", "glycan_involvement": "Glycan shielding may promote persistent infection and immune activation", "mechanism": "gp120-driven immune dysregulation leads to chronic oral inflammation", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "medium", "disease": "Immune-mediated glomerulonephritis", "glycan_involvement": "Glycosylation of viral proteins influences immune complex formation", "mechanism": "Immune complexes containing viral glycoproteins deposit in glomeruli", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152317" }, { "confidence": "high", "disease": "Feline Immunodeficiency Virus Infection (FIV)", "glycan_involvement": "Glycosylation affects antigenicity and assay sensitivity", "mechanism": "Antibodies to gp40 are detected in diagnostic assays for FIV", "protein": "gp40", "relationship_type": "biomarker", "source_pmcid": "PMC7152317" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation critical for receptor binding and immune evasion.", "mechanism": "Mediates viral entry via binding to host cell receptors.", "protein": "Viral envelope glycoproteins (spikes)", "relationship_type": "causal", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Viral infectious diseases (general)", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Inhibits viral replication and enhances antigen presentation.", "protein": "Interferon-alpha (IFN-\u03b1)", "relationship_type": "protective", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Viral infectious diseases (general)", "glycan_involvement": "Glycosylation required for function.", "mechanism": "Antiviral activity via induction of antiviral state in cells.", "protein": "Interferon-beta (IFN-\u03b2)", "relationship_type": "protective", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Viral infectious diseases (general)", "glycan_involvement": "Glycosylation required for stability and activity.", "mechanism": "Activates macrophages and enhances immune response.", "protein": "Interferon-gamma (IFN-\u03b3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Viral infectious diseases (general)", "glycan_involvement": "Glycosylation affects antigen presentation.", "mechanism": "Presents viral antigens to cytotoxic T cells.", "protein": "Major histocompatibility complex (MHC) class I", "relationship_type": "biomarker", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Viral infectious diseases (general)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Presents viral antigens to helper T cells.", "protein": "Major histocompatibility complex (MHC) class II", "relationship_type": "biomarker", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates receptor binding and antigenicity.", "mechanism": "Mediates viral attachment and entry into host cells.", "protein": "Influenza hemagglutinin", "relationship_type": "causal", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects immunogenicity.", "mechanism": "Used in diagnosis and as a vaccine antigen.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Measles, Mumps, Rubella, Rabies, Chickenpox, Smallpox, Yellow fever", "glycan_involvement": "Glycosylation influences antigenicity and immune response.", "mechanism": "Structural proteins targeted by vaccines.", "protein": "Viral capsid glycoproteins", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavy glycosylation shields epitopes from immune recognition.", "mechanism": "Mediates viral entry and is target for neutralizing antibodies.", "protein": "HIV envelope glycoprotein (gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7152364" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Target of neutralizing antibodies in vaccines; correlates with protection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity.", "mechanism": "Vaccine antigen; anti-HBsAg titers correlate with protection.", "protein": "HBV Surface Antigen (HBsAg)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield mediates immune evasion.", "mechanism": "Target of broadly neutralizing antibodies; vaccine development focus.", "protein": "HIV Envelope Glycoprotein (Env)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus (RSV) Disease", "glycan_involvement": "Glycosylation affects antigenicity and immunopathology.", "mechanism": "Target of neutralizing antibodies; vaccine candidate.", "protein": "RSV Fusion Glycoprotein (F)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Human Papillomavirus (HPV)-associated Disease", "glycan_involvement": "Glycosylation influences particle assembly and immunogenicity.", "mechanism": "Self-assembles into virus-like particles for vaccines; induces protective immunity.", "protein": "HPV L1 Protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) Disease", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Target of vaccine-induced antibodies; candidate for vaccine development.", "protein": "CMV Glycoprotein B (gB)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation affects antigenicity.", "mechanism": "Target of neutralizing antibodies; vaccine antigen.", "protein": "Measles Virus Hemagglutinin", "protein_enriched": { "function": "Attaches the virus to the human SLAMF1/CD150 receptor for entry into host dendritic cells, macrophages, activated memory T cells and naive or memory B cells, thereby explaining the long immunosuppress", "gene_name": "H", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P08362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation required for immunogenicity.", "mechanism": "Target of neutralizing antibodies; vaccine antigen.", "protein": "Rabies Virus Glycoprotein (G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Rotavirus Gastroenteritis", "glycan_involvement": "Glycosylation influences antigenicity and vaccine efficacy.", "mechanism": "Target of neutralizing antibodies; vaccine antigen.", "protein": "Rotavirus VP7", "protein_enriched": { "function": "Accumulates harmlessly in the cytoplasmic membrane until it reaches a critical concentration that triggers the formation of micron-scale pores (holes) causing host cell membrane disruption and endolys", "gene_name": "14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11188" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Target of neutralizing antibodies; included in vaccine formulations.", "protein": "Influenza Neuraminidase (NA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152391" }, { "confidence": "high", "disease": "Smallpox (Variola virus infection)", "glycan_involvement": "Glycosaminoglycan binding retains protein at infection site.", "mechanism": "Binds type I IFN, blocks IFN signaling, promotes viral replication and virulence.", "protein": "VACV Type I Interferon Binding Protein (IFNBP)", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Epstein-Barr Virus-Associated Lymphoproliferative Disease", "glycan_involvement": "Secreted glycoprotein; glycosylation aids stability and secretion.", "mechanism": "Suppresses cellular immunity by inhibiting IFN-\u03b3, facilitating immune evasion.", "protein": "EBV IL-10 Homologue", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Kaposi's Sarcoma", "glycan_involvement": "Secreted glycoprotein; glycosylation enhances cytokine activity.", "mechanism": "Promotes B cell proliferation, contributing to tumorigenesis.", "protein": "KSHV IL-6 Homologue", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Mousepox (ECTV infection)", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability.", "mechanism": "Inhibits caspase-1, blocks IL-1\u03b2/IL-18 activation, reduces immunopathology.", "protein": "VACV CrmA (Cytokine Response Modifier A)", "relationship_type": "protective", "source_pmcid": "PMC7152433" }, { "confidence": "medium", "disease": "Smallpox (Variola virus infection)", "glycan_involvement": "Intracellular glycoprotein; glycosylation may modulate function.", "mechanism": "Binds dsRNA, inhibits PKR and 2\u20325\u2032OAS, blocks antiviral response.", "protein": "VACV E3 Protein", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Heavily N-glycosylated; glycans shield from immune detection.", "mechanism": "Acts as competitive substrate for PKR, blocks eIF-2\u03b1 phosphorylation, evades IFN response.", "protein": "Hepatitis C Virus E2 Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Molluscum Contagiosum", "glycan_involvement": "Secreted glycoprotein; glycosylation enhances serum half-life.", "mechanism": "Binds IL-18, downregulates IFN-\u03b3, prevents inflammation.", "protein": "Molluscum Contagiosum Virus IL-18 Binding Protein", "relationship_type": "protective", "source_pmcid": "PMC7152433" }, { "confidence": "medium", "disease": "Human Cytomegalovirus Infection", "glycan_involvement": "Membrane glycoprotein; glycosylation affects receptor interactions.", "mechanism": "Inhibits T cell proliferation, modulates immune response.", "protein": "Human Cytomegalovirus UL144", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Immunopathology (Cytokine Storm)", "glycan_involvement": "Secreted glycoprotein; glycosylation required for function.", "mechanism": "Acts as decoy for IL-1\u03b2, reduces immunopathology during infection.", "protein": "VACV Secreted IL-1 Receptor", "relationship_type": "protective", "source_pmcid": "PMC7152433" }, { "confidence": "medium", "disease": "Epstein-Barr Virus-Associated Lymphoproliferative Disease", "glycan_involvement": "Membrane glycoprotein; glycosylation modulates receptor clustering.", "mechanism": "Mimics TNFR signaling, promotes B cell proliferation and survival.", "protein": "EBV Latent Membrane Protein 1", "relationship_type": "causal", "source_pmcid": "PMC7152433" }, { "confidence": "high", "disease": "Influenza pneumonia", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry into respiratory epithelial cells via sialic acid binding.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "Influenza pneumonia", "glycan_involvement": "Glycosylation affects enzymatic activity and antigenicity.", "mechanism": "Cleaves sialic acids to facilitate viral release from host cells.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "RSV pneumonia", "glycan_involvement": "N-glycosylation critical for protein folding and immune evasion.", "mechanism": "Mediates fusion of viral and host cell membranes.", "protein": "RSV Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes from immune recognition.", "mechanism": "Mediates viral entry via ACE2 receptor binding.", "protein": "Coronavirus Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry via DPP4 receptor binding.", "protein": "Coronavirus Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "medium", "disease": "Hantavirus Pulmonary Syndrome (HPS)", "glycan_involvement": "N-glycosylation required for proper folding and infectivity.", "mechanism": "Mediates attachment and entry into endothelial cells.", "protein": "Hantavirus glycoproteins (Gn/Gc)", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "Cytomegalovirus (CMV) pneumonia", "glycan_involvement": "N-glycosylation modulates immune recognition and infectivity.", "mechanism": "Essential for viral entry and cell-to-cell spread.", "protein": "CMV glycoprotein B (gB)", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "medium", "disease": "Herpes simplex virus (HSV) pneumonia", "glycan_involvement": "N-glycosylation affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to host receptors.", "protein": "HSV glycoprotein D (gD)", "protein_enriched": { "function": "In epithelial cells, the heterodimer gE/gI is required for the cell-to-cell spread of the virus, by sorting nascent virions to cell junctions. Once the virus reaches the cell junctions, virus particle", "gene_name": "gE", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04488" }, "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "medium", "disease": "Adenovirus pneumonia", "glycan_involvement": "O-glycosylation may affect tropism and immune recognition.", "mechanism": "Mediates attachment to host cell receptors (CAR).", "protein": "Adenovirus Fiber protein", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "medium", "disease": "Measles pneumonia", "glycan_involvement": "N-glycosylation modulates receptor binding and antigenicity.", "mechanism": "Mediates viral attachment to host cell receptors.", "protein": "Measles virus Hemagglutinin (H)", "relationship_type": "causal", "source_pmcid": "PMC7152475" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Increased sialylation on cell surface glycoproteins", "mechanism": "Aberrant overexpression of sialic acid on glycoproteins correlates with tumor progression and metastasis.", "protein": "Sialic acid-containing glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC7153339" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Sialic acid ligands mediate targeting", "mechanism": "CD22 is targeted by sialic acid-conjugated nanoparticles for drug delivery in B cell-derived autoimmune diseases.", "protein": "CD22", "protein_enriched": { "function": "Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and tra", "gene_name": "CD22", "glycan_count": 4, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G22768VO", "G81315DD", "G62765YT", "G49108TO" ], "uniprot_id": "P20273" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7153339" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialylated glycoproteins act as viral receptors", "mechanism": "HA binds to sialic acid on host cell glycoproteins to initiate infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Sepsis/ARDS", "glycan_involvement": "Sialic acid ligands induce Siglec-E oligomerization", "mechanism": "Siglec-E ligand nanoparticles modulate inflammatory response, reducing acute inflammation in sepsis/ARDS.", "protein": "Siglec-E", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Changes in O-glycosylation patterns", "mechanism": "Altered O-glycosylation of MUC2 mucin detected in colon cancer biopsies.", "protein": "MUC2 mucin", "relationship_type": "biomarker", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Hemangioma", "glycan_involvement": "Modified sialylation of gangliosides", "mechanism": "Unusual ganglioside glycoforms detected in brain hemangioma tumor tissue.", "protein": "Gangliosides (e.g., GD2, GM4)", "relationship_type": "biomarker", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Sialylation of TF antigen", "mechanism": "Sialylated Thomsen-Friedenreich antigens identified as cancer-associated glycoprotein markers.", "protein": "Thomsen-Friedenreich antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7153339" }, { "confidence": "high", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Sialic acid-E-selectin binding mediates targeting", "mechanism": "Sialic acid-conjugated nanoparticles target E-selectin on inflamed endothelial cells to deliver dexamethasone and ameliorate AKI.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Sialic acid modification enhances BBB crossing and A\u03b2 targeting", "mechanism": "Sialic acid-coated nanoparticles cross BBB and bind A\u03b2 plaques for imaging and potential therapy.", "protein": "\u03b2-amyloid (A\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7153339" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Sialylation of plasminogen", "mechanism": "Sialylated plasminogen detected as a marker in cancer tissue using nano-LC-MALDI-TOF-MS.", "protein": "Plasminogen", "relationship_type": "biomarker", "source_pmcid": "PMC7153339" }, { "confidence": "high", "disease": "Encephalitis", "glycan_involvement": "Heavily glycosylated; glycosylation affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry into CNS cells via receptor binding and fusion; determines neurovirulence and cell tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "high", "disease": "Demyelination", "glycan_involvement": "Glycosylation modulates immune recognition and cell entry.", "mechanism": "Alters cell tropism and immune response, leading to demyelination in persistent infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "high", "disease": "Multiple sclerosis (MS, model)", "glycan_involvement": "Glycosylation influences S protein function and immune response.", "mechanism": "MHV S protein-mediated demyelination is used as a model for MS.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/model", "source_pmcid": "PMC7153443" }, { "confidence": "high", "disease": "Encephalitis", "glycan_involvement": "CEACAM-1a is a glycoprotein; glycosylation may affect virus binding.", "mechanism": "Acts as the main receptor for MHV S protein, enabling CNS infection.", "protein": "CEACAM-1a", "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "high", "disease": "Encephalitis", "glycan_involvement": "Sialic acid residues are essential for viral attachment.", "mechanism": "Serve as receptors for HCoV-OC43 S protein, mediating neurotropic infection.", "protein": "Sialylated cell surface glycans", "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Binds and modifies sialylated glycans.", "mechanism": "Enhances infectivity and spread in CNS by acting as a secondary receptor-binding protein.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "facilitative", "source_pmcid": "PMC7153443" }, { "confidence": "medium", "disease": "Hepatitis", "glycan_involvement": "Predicted glycoprotein; glycosylation may affect stability/function.", "mechanism": "Antagonizes interferon response, promoting hepatitis in MHV-A59 infection.", "protein": "ORF2a (ns2)", "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "low", "disease": "Encephalitis", "glycan_involvement": "Highly glycosylated; glycan structures may influence virus binding.", "mechanism": "Can serve as an alternative receptor for some MHV strains in CNS.", "protein": "Pregnancy-specific glycoprotein (PSG)", "relationship_type": "potential receptor", "source_pmcid": "PMC7153443" }, { "confidence": "medium", "disease": "Blood-brain barrier disruption", "glycan_involvement": "MMP3 is a glycoprotein; glycosylation affects secretion/activity.", "mechanism": "Upregulated in astrocytes during MHV infection, contributing to BBB breakdown.", "protein": "Matrix metalloproteinase 3 (MMP3)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7153443" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation required for proper assembly and function.", "mechanism": "Essential for virion assembly and infectivity; interacts with S and N proteins.", "protein": "Transmembrane glycoprotein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "structural/causal", "source_pmcid": "PMC7153443" }, { "confidence": "high", "disease": "HIV-1 encephalitis", "glycan_involvement": "Glycosylation required for surface expression and antiviral function.", "mechanism": "Tetherin retains budding HIV-1 virions on cell surface, preventing release.", "protein": "CD317/tetherin", "relationship_type": "protective", "source_pmcid": "PMC7153449" }, { "confidence": "high", "disease": "HIV-1 encephalitis", "glycan_involvement": "Heavily glycosylated; glycans shield from immune recognition.", "mechanism": "Mediates viral entry and cell-cell fusion (syncytia formation).", "protein": "HIV-1 Env glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "high", "disease": "HSV-1 encephalitis", "glycan_involvement": "Glycosylation modulates immune recognition and function.", "mechanism": "Mediates viral entry and immune evasion.", "protein": "HSV-1 glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "medium", "disease": "SIV CNS infection", "glycan_involvement": "Glycosylation required for function and immune evasion.", "mechanism": "Mediates viral entry and antagonizes tetherin.", "protein": "SIV Env glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "medium", "disease": "Filovirus infection", "glycan_involvement": "Glycosylation essential for antagonizing tetherin.", "mechanism": "Blocks tetherin-mediated restriction of viral release.", "protein": "Filovirus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "medium", "disease": "HHV-8 infection", "glycan_involvement": "K5 is a glycoprotein E3 ligase; glycosylation may affect localization/function.", "mechanism": "Ubiquitinates and degrades tetherin, promoting viral release.", "protein": "HHV-8 K5", "protein_enriched": { "function": "Modulates host cell cycle progression and apoptotic signaling pathways by acting as a cyclin. Forms an active kinase complex with cellular CDK6 kinase. Promotes host S-phase entry of quiescent cells a", "gene_name": "ORF72", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q77Q36" }, "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "medium", "disease": "VSV encephalitis", "glycan_involvement": "Secreted form is glycosylated; glycosylation may affect secretion.", "mechanism": "ISG15 conjugation restricts viral replication.", "protein": "ISG15", "protein_enriched": { "function": "Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated p", "gene_name": "ISG15", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05161" }, "relationship_type": "protective", "source_pmcid": "PMC7153449" }, { "confidence": "high", "disease": "Viral encephalitis (general)", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "Presents viral peptides to CD8+ T cells; neurons have low expression, limiting immune clearance.", "protein": "Major Histocompatibility Complex (MHC) I", "relationship_type": "protective", "source_pmcid": "PMC7153449" }, { "confidence": "high", "disease": "Diabetes-associated inflammation", "glycan_involvement": "RAGE is a glycoprotein; ligand binding involves glycan modifications.", "mechanism": "RAGE engagement by glycation end-products triggers inflammation.", "protein": "RAGE", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "Aberrant glycosylation leads to ER stress and DAMP signaling.", "mechanism": "Viral glycoprotein accumulation can trigger unfolded protein response and neurodegeneration.", "protein": "Viral glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC7153449" }, { "confidence": "high", "disease": "PML", "glycan_involvement": "VP1 binds sialic acid-containing glycans on host cells for entry.", "mechanism": "JC virus infects oligodendrocytes via VP1-mediated attachment, leading to lytic destruction and demyelination.", "protein": "JC virus VP1", "relationship_type": "causal", "source_pmcid": "PMC7155579" }, { "confidence": "medium", "disease": "ADEM", "glycan_involvement": "Glycosylation of MOG may influence antigenicity and immune recognition.", "mechanism": "Autoimmune response against MOG following viral infection triggers demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC7155579" }, { "confidence": "medium", "disease": "MS", "glycan_involvement": "Altered glycosylation may modulate immune response to MOG.", "mechanism": "Autoantibodies to MOG contribute to demyelination in MS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC7155579" }, { "confidence": "medium", "disease": "MS", "glycan_involvement": "MAG contains sialic acid-binding domains; glycosylation affects function.", "mechanism": "Loss of MAG is an early marker of demyelination in MS lesions.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "causal", "source_pmcid": "PMC7155579" }, { "confidence": "medium", "disease": "ADEM", "glycan_involvement": "Glycosylation patterns influence immunogenicity and molecular mimicry.", "mechanism": "Viral glycoproteins trigger host immune response leading to cross-reactivity with myelin antigens.", "protein": "Viral envelope glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC7155579" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "N-glycosylation of S protein is essential for proper folding and receptor binding.", "mechanism": "Mediates viral attachment and entry into host respiratory epithelial cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7155630" }, { "confidence": "high", "disease": "Turkey Coronavirus Enteritis", "glycan_involvement": "Glycosylation modulates host cell tropism and immune evasion.", "mechanism": "Facilitates viral entry into intestinal epithelial cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7155630" }, { "confidence": "medium", "disease": "Avian Nephritis", "glycan_involvement": "Glycosylation affects receptor specificity and pathogenicity.", "mechanism": "Determines tissue tropism for renal cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7155630" }, { "confidence": "medium", "disease": "Infectious Bronchitis", "glycan_involvement": "N-glycosylation influences virion stability and infectivity.", "mechanism": "Essential for viral assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7155630" }, { "confidence": "medium", "disease": "Turkey Coronavirus Enteritis", "glycan_involvement": "Glycosylation modulates receptor binding and immune recognition.", "mechanism": "Facilitates binding to sialic acid-containing receptors in the gut.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "causal", "source_pmcid": "PMC7155630" }, { "confidence": "high", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation sites influence antigenicity and immune response.", "mechanism": "Target for neutralizing antibodies and vaccine development.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7155630" }, { "confidence": "medium", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation patterns distinguish pathogenic strains.", "mechanism": "Variation in S glycoprotein sequence/glycosylation used for strain typing.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7155630" }, { "confidence": "low", "disease": "Infectious Bronchitis", "glycan_involvement": "Glycosylation status may affect detection sensitivity.", "mechanism": "M protein presence indicates active infection.", "protein": "Membrane glycoprotein (M)", "relationship_type": "biomarker", "source_pmcid": "PMC7155630" }, { "confidence": "low", "disease": "Turkey Coronavirus Enteritis", "glycan_involvement": "Glycosylation affects drug binding sites.", "mechanism": "Potential target for antiviral drugs blocking receptor binding.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7155630" }, { "confidence": "low", "disease": "Avian Nephritis", "glycan_involvement": "Glycosylation impacts immunogenicity.", "mechanism": "Target for vaccine strategies to prevent renal tropism.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7155630" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Heavily glycosylated; glycosylation is critical for proper folding, immune evasion, and receptor binding.", "mechanism": "Mediates viral attachment and entry into host cells, enabling MERS-CoV infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157455" }, { "confidence": "high", "disease": "Severe pneumonia", "glycan_involvement": "Glycosylation shields immunogenic epitopes, contributing to pathogenicity.", "mechanism": "Facilitates viral entry into lower respiratory tract cells, leading to severe pneumonia.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycans modulate host immune recognition and response.", "mechanism": "Viral entry via S protein triggers severe inflammatory response in lungs.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157455" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation affects antibody accessibility and vaccine design.", "mechanism": "Targeted by monoclonal and polyclonal antibodies, and vaccine candidates.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation enhances antigenicity for serological detection.", "mechanism": "Used as antigen in diagnostic ELISA assays for MERS-CoV infection.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation influences assay sensitivity and specificity.", "mechanism": "S1 subunit used in serological assays for MERS-CoV diagnosis.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycan shield may limit neutralizing antibody binding.", "mechanism": "Targeted by convalescent plasma and neutralizing antibodies.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation must be considered in vaccine antigen design.", "mechanism": "Basis for experimental vaccines in humans and camels.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7157455" }, { "confidence": "low", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Viral tropism for renal epithelial cells mediated by S protein.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157455" }, { "confidence": "medium", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation patterns may affect cross-species transmission.", "mechanism": "Facilitates zoonotic transmission from camels to humans.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157455" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "NS1 is a secreted glycoprotein; glycosylation is essential for secretion and immune evasion.", "mechanism": "NS1 inhibits terminal complement pathway by binding vitronectin, blocking membrane attack complex formation.", "protein": "NS1", "protein_enriched": { "function": "Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage an", "gene_name": "NS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03496" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "Zika virus disease", "glycan_involvement": "Glycosylation of E protein and host GAGs are critical for attachment and infection.", "mechanism": "Envelope protein binds host glycosaminoglycans (heparin) to mediate cell entry.", "protein": "Envelope glycoprotein E (Zika virus)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA recognizes host sialoglycoproteins; glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral entry by binding sialic acid on host cells; used as a diagnostic target.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "NA activity depends on glycan recognition and cleavage.", "mechanism": "NA cleaves sialic acid to facilitate viral release; targeted by diagnostics and antivirals.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC7157476" }, { "confidence": "medium", "disease": "Herpes simplex virus infection", "glycan_involvement": "gG is a glycoprotein; glycosylation may affect chemokine binding.", "mechanism": "gG binds host chemokines, modulating immune response and enhancing cell migration.", "protein": "Glycoprotein G (gG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/immune modulation", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and mediate host interactions.", "mechanism": "gp120 binds CD4 and glycosaminoglycans (e.g., heparin) for viral entry; target for diagnostics and inhibitors.", "protein": "gp120", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7157476" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Membrane binding may involve interactions with glycosylated lipids.", "mechanism": "Gag binds plasma membrane for viral assembly; defects impair virion production.", "protein": "Gag", "relationship_type": "causal", "source_pmcid": "PMC7157476" }, { "confidence": "medium", "disease": "Hand, foot and mouth disease", "glycan_involvement": "Capsid protein may interact with host glycans for cell entry.", "mechanism": "VP1 is a major capsid protein of EV71, used as a diagnostic marker.", "protein": "VP1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "COVID-19/SARS/MERS", "glycan_involvement": "Heavily glycosylated; glycans modulate receptor binding and immune evasion.", "mechanism": "Spike protein mediates host receptor binding and viral entry; target for diagnostics and inhibitors.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7157476" }, { "confidence": "medium", "disease": "Hepatitis B virus-related hepatocellular carcinoma", "glycan_involvement": "PreS1 is a glycoprotein; glycosylation may affect targeting.", "mechanism": "PreS1 peptide targets cells overexpressing SERPINB3 in hepatocellular carcinoma.", "protein": "PreS1 (HBV surface protein)", "relationship_type": "therapeutic_target/biomarker", "source_pmcid": "PMC7157476" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects receptor binding, immune evasion, and antigenicity.", "mechanism": "Mediates viral entry via ACE2 receptor binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor interaction and immune recognition.", "mechanism": "Mediates viral entry via DPP4 (CD26) receptor binding and fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "high", "disease": "Common cold", "glycan_involvement": "Glycosylation influences tropism and immune escape.", "mechanism": "Attachment and entry of HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1 to respiratory epithelium.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation modulates fusion and antigenicity.", "mechanism": "Facilitates infection of lower respiratory tract cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation sites are key antigenic determinants.", "mechanism": "Targeted by neutralizing monoclonal antibodies and vaccine candidates.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7157479" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Acquired via recombination; glycosylation affects function.", "mechanism": "Enhances virulence and cell tropism in HCoV-OC43 and HCoV-HKU1.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "enhancer/causal", "source_pmcid": "PMC7157479" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Ectodomain glycosylation may affect assembly and immune recognition.", "mechanism": "Essential for virus assembly and packaging.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Required for efficient assembly; deletion attenuates virus for vaccine development.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7157479" }, { "confidence": "medium", "disease": "Feline infectious peritonitis", "glycan_involvement": "Glycosylation affects tropism and immune response.", "mechanism": "Mediates entry and cell fusion in FIPV.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "medium", "disease": "Multiple sclerosis-like demyelinating disease (in mice)", "glycan_involvement": "Glycosylation modulates neuroinvasion.", "mechanism": "MHV spike mediates neurotropism and demyelination.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7157479" }, { "confidence": "high", "disease": "Astrogliosis", "glycan_involvement": "Glycosylation may affect GFAP stability and detection.", "mechanism": "GFAP upregulation marks astrocyte proliferation in response to CNS injury.", "protein": "Glial Fibrillary Acidic Protein (GFAP)", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "Gfap", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G26549SM", "G49108TO" ], "uniprot_id": "P03995" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Demyelination", "glycan_involvement": "Glycosylation may regulate Olig2 localization/function.", "mechanism": "Olig2 marks oligodendrocyte lineage cells involved in myelination; loss linked to demyelination.", "protein": "Oligodendrocyte Transcription Factor 2 (Olig2)", "protein_enriched": { "function": "Required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. Functions together with ZNF488 to promote olig", "gene_name": "OLIG2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13516" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation modulates pump localization and activity.", "mechanism": "Altered Na+/K+-ATPase function disrupts membrane potential, contributing to epileptic activity.", "protein": "Na+/K+-ATPase", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation affects channel gating and surface expression.", "mechanism": "Channel mutations or dysfunction alter neuronal excitability, leading to seizures.", "protein": "Voltage-Gated Sodium Channel (Nav)", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Hydrocephalus", "glycan_involvement": "Glycosylation critical for barrier integrity.", "mechanism": "Barrier glycoproteins regulate CSF production; dysfunction can lead to hydrocephalus.", "protein": "Choroid Plexus Epithelial Cell Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "high", "disease": "Blood-Brain Barrier Dysfunction", "glycan_involvement": "Glycosylation essential for tight junction formation.", "mechanism": "Endothelial glycoproteins maintain barrier properties; disruption leads to CNS pathology.", "protein": "Endothelial Cell Glycoproteins (Blood-Brain Barrier)", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Central Chromatolysis", "glycan_involvement": "Glycosylation modulates receptor trafficking and ligand binding.", "mechanism": "Altered receptor function affects neuronal survival and response to injury.", "protein": "Neurotransmitter Receptors (Ionotropic/Metabotropic)", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Spina Bifida", "glycan_involvement": "Glycosylation required for ECM assembly.", "mechanism": "Defective basement membrane glycoproteins impair neural tube closure.", "protein": "Basement Membrane Glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7158194" }, { "confidence": "medium", "disease": "Encephalitis", "glycan_involvement": "Glycosylation may affect Iba1 detection.", "mechanism": "Iba1 marks activated microglia in CNS inflammation.", "protein": "Ionized Calcium Binding Adapter Molecule 1 (Iba1)", "protein_enriched": { "function": "Is, with PLP, the most abundant protein component of the myelin membrane in the CNS. Has a role in both the formation and stabilization of this compact multilayer arrangement of bilayers. Each splice ", "gene_name": "Mbp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02688" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158194" }, { "confidence": "low", "disease": "Axonopathy", "glycan_involvement": "Glycosylation may regulate Olig2 stability.", "mechanism": "Olig2 expression reflects oligodendrocyte response to axonal injury.", "protein": "Oligodendrocyte Transcription Factor 2 (Olig2)", "protein_enriched": { "function": "Required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. Functions together with ZNF488 to promote olig", "gene_name": "OLIG2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q13516" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158194" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield from immune recognition and mediate receptor binding.", "mechanism": "gp120 binds CD4 receptor and coreceptors to mediate HIV entry into T cells.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialic acid (glycan) is the viral receptor; HA is also glycosylated.", "mechanism": "HA binds sialic acid residues on host cell glycoproteins to mediate viral entry.", "protein": "HA (hemagglutinin)", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "gD is glycosylated; host HSPG (glycosaminoglycan) acts as attachment factor.", "mechanism": "gD binds to nectin-1/HVEM on host cells to mediate HSV entry.", "protein": "gD", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "gB is glycosylated; interacts with host glycosaminoglycans.", "mechanism": "gB mediates membrane fusion during HSV entry.", "protein": "gB", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "E2 is glycosylated; host SR-B1 and LDL receptor (glycoproteins) act as attachment factors.", "mechanism": "E2 binds CD81 and other receptors to mediate HCV entry.", "protein": "E2", "protein_enriched": { "function": "", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q66525" }, "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Pre-S1 is glycosylated; host HSPG acts as attachment factor.", "mechanism": "Pre-S1 domain binds NTCP receptor for HBV entry.", "protein": "Pre-S1", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "G protein is glycosylated; host receptor is a glycoprotein.", "mechanism": "G protein binds NCAM-1/CD56 to mediate rabies virus entry.", "protein": "G protein", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Spike is glycosylated; glycosylation affects receptor binding and immune evasion.", "mechanism": "Spike protein binds ACE2 receptor to mediate SARS-CoV entry.", "protein": "Spike", "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "medium", "disease": "Poliomyelitis", "glycan_involvement": "VP1 is a capsid protein; host receptor is a glycoprotein.", "mechanism": "VP1 binds PVR/CD155 to mediate poliovirus entry.", "protein": "VP1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "Epstein-Barr virus infection", "glycan_involvement": "gp350 is glycosylated; host HSPG acts as attachment factor.", "mechanism": "gp350 binds CD21 on B cells to mediate EBV entry.", "protein": "gp350", "protein_enriched": { "function": "Plays an essential role in virion nuclear egress, the first step of virion release from infected cell. Within the host nucleus, NEC1 interacts with the newly formed capsid through the vertexes and dir", "gene_name": "NEC2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03185" }, "relationship_type": "causal", "source_pmcid": "PMC7158286" }, { "confidence": "high", "disease": "X-linked muscular dystrophy", "glycan_involvement": "Dystrophin-associated glycoprotein complex requires proper glycosylation for function.", "mechanism": "Loss of dystrophin disrupts sarcolemmal stability, leading to muscle fiber necrosis.", "protein": "Dystrophin", "protein_enriched": { "function": "Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (", "gene_name": "DMD", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G59324HL", "G88891KO" ], "uniprot_id": "P11532" }, "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "high", "disease": "X-linked muscular dystrophy", "glycan_involvement": "N- and O-glycosylation critical for complex stability.", "mechanism": "Defective glycosylation impairs complex assembly, weakening muscle membrane.", "protein": "Dystrophin-associated glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "high", "disease": "Myasthenia gravis", "glycan_involvement": "Glycosylation affects antigenicity and receptor stability.", "mechanism": "Autoantibodies target glycosylated receptor, impairing neuromuscular transmission.", "protein": "Acetylcholine receptor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "medium", "disease": "Cachexia", "glycan_involvement": "Glycosylation modulates secretion and activity.", "mechanism": "Overexpression leads to muscle atrophy.", "protein": "Myostatin", "protein_enriched": { "function": "Acts specifically as a negative regulator of skeletal muscle growth", "gene_name": "MSTN", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G62765YT" ], "uniprot_id": "O14793" }, "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "medium", "disease": "Polymyositis", "glycan_involvement": "Glycosylation influences immune complex formation.", "mechanism": "IgA deposits may be present in immune-mediated muscle inflammation.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158298" }, { "confidence": "high", "disease": "Glycogen storage disease", "glycan_involvement": "Enzyme activity directly affects glycogen (a glucose polymer).", "mechanism": "Deficiency leads to abnormal glycogen accumulation in muscle.", "protein": "Glycogen branching enzyme (GBE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "high", "disease": "Equine polysaccharide storage myopathy (EPSSM)", "glycan_involvement": "Enzyme regulates glycogen synthesis.", "mechanism": "Mutation causes abnormal glycogen accumulation in muscle fibers.", "protein": "Glycogen synthase 1 (GYS1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7158298" }, { "confidence": "medium", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may affect serum half-life.", "mechanism": "Muscle damage releases CK into serum.", "protein": "Creatine kinase (CK)", "protein_enriched": { "function": "Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in ", "gene_name": "CKB", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P12277" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158298" }, { "confidence": "low", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may affect detection.", "mechanism": "Released from damaged muscle fibers.", "protein": "Fatty acid binding protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7158298" }, { "confidence": "low", "disease": "Rhabdomyolysis", "glycan_involvement": "Glycosylation may influence stability.", "mechanism": "Released into serum after muscle injury.", "protein": "Carbonic anhydrase III", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7158298" }, { "confidence": "high", "disease": "Fucosidosis", "glycan_involvement": "Impaired degradation of glycoprotein N-linked fucosylated oligosaccharides.", "mechanism": "Deficiency leads to accumulation of fucose-containing glycoproteins in lysosomes, causing neurodegeneration.", "protein": "\u03b1-L-Fucosidase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "\u03b1-Mannosidosis", "glycan_involvement": "Impaired degradation of N-linked glycoprotein oligosaccharides.", "mechanism": "Deficiency causes accumulation of mannose-rich oligosaccharides in lysosomes, leading to CNS and systemic signs.", "protein": "\u03b1-D-Mannosidase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "\u03b2-Mannosidosis", "glycan_involvement": "Impaired glycoprotein oligosaccharide catabolism.", "mechanism": "Deficiency results in storage of \u03b2-mannosyl oligosaccharides, causing neurodegeneration.", "protein": "\u03b2-D-Mannosidase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "Mucolipidosis II (I-cell disease)", "glycan_involvement": "Defective N-glycan phosphorylation on lysosomal enzymes.", "mechanism": "Deficiency prevents mannose-6-phosphate tagging of lysosomal enzymes, causing mislocalization and substrate accumulation.", "protein": "N-acetylglucosamine-1-phosphotransferase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "GM1-gangliosidosis", "glycan_involvement": "Impaired degradation of glycoprotein and glycolipid glycans.", "mechanism": "Deficiency leads to accumulation of GM1 ganglioside and glycoprotein-derived oligosaccharides in neurons.", "protein": "\u03b2-D-Galactosidase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "GM2-gangliosidosis (Tay-Sachs disease)", "glycan_involvement": "Impaired degradation of glycoprotein and glycolipid glycans.", "mechanism": "Deficiency causes GM2 ganglioside and glycoprotein oligosaccharide accumulation in neurons.", "protein": "\u03b2\u2013N-acetyl hexosaminidase A", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "GM2AB-gangliosidosis", "glycan_involvement": "Impaired glycolipid and glycoprotein catabolism.", "mechanism": "Deficiency impairs presentation of GM2 ganglioside to hexosaminidase A, causing substrate accumulation.", "protein": "GM2 activator protein", "protein_enriched": { "function": "The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and ", "gene_name": "GM2A", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P17900" }, "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "Mucopolysaccharidosis VI (Maroteaux-Lamy disease)", "glycan_involvement": "Impaired degradation of glycosaminoglycan (GAG) side chains on proteoglycans.", "mechanism": "Deficiency leads to dermatan sulfate accumulation, causing skeletal and neurologic disease.", "protein": "N-acetylgalactosamine 4-sulfatase (Arylsulfatase B)", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "Mucopolysaccharidosis VII (Sly syndrome)", "glycan_involvement": "Impaired degradation of glycosaminoglycan chains.", "mechanism": "Deficiency causes accumulation of GAGs, leading to multisystem disease.", "protein": "\u03b2\u2013D-glucuronidase", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "Metachromatic leukodystrophy", "glycan_involvement": "Impaired degradation of sulfated glycolipids and glycoproteins.", "mechanism": "Deficiency leads to sulfatide accumulation, causing demyelination and neurodegeneration.", "protein": "Arylsulfatase A", "relationship_type": "causal", "source_pmcid": "PMC7158336" }, { "confidence": "high", "disease": "Leukocytic tumors", "glycan_involvement": "Glycosylation affects antibody recognition and cell surface expression.", "mechanism": "CD45 is expressed on all leukocytes and used to identify leukocytic origin in tumors.", "protein": "CD45", "protein_enriched": { "function": "Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor (PubMed:35767951). Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first ", "gene_name": "PTPRC", "glycan_count": 126, "glycosylation_sites_count": 17, "glytoucan_ids": [ "G22310AV", "G52527GH", "G57321FI", "G53434XO", "G58001LT", "G43417UB", "G05962QB", "G09831WQ", "G27058EU", "G32788FZ", "G35541EV", "G62765YT", "G67164EE", "G79666IR", "G80479JV", "G80920RR", "G87123QX", "G93718GY", "G06356OH", "G13694XX", "G31665QC", "G34617SM", "G37881RL", "G47518TP", "G48414YA", "G57888GL", "G62461SM", "G74728JK", "G81263BG", "G82830MN", "G84452RH", "G90093AU", "G96577RX", "G38663NM", "G51413EV", "G04657PL", "G35029YA", "G45395BF", "G46691LC", "G57776ZS", "G70232NH", "G70441OD", "G72787SB", "G81637OR", "G90659AW", "G95046LV", "G95177YH", "G03382KH", "G23863VK", "G72797UR", "G50045TK", "G59536GA", "G66760KM", "G75983OB", "G86795LJ", "G31852PQ", "G40926MX", "G41247ZX", "G59626AS", "G05724UK", "G06110VR", "G23294PN", "G25451PN", "G39188ZX", "G82463GQ", "G11629QQ", "G00031MO", "G01614ZM", "G02679YX", "G04689DA", "G15956KF", "G16828VN", "G18214MO", "G19399OS", "G19490DN", "G19972YZ", "G20425TQ", "G20697MN", "G23546LY", "G24748QU", "G25520XG", "G26142HL", "G29931IJ", "G31544HA", "G36191CD", "G36436SB", "G45300SB", "G45711GR", "G46576CR", "G47012YE", "G49105NA", "G50755IT", "G50783JY", "G52934AK", "G54706BB", "G55220VL", "G55661CO", "G56682BC", "G60145BJ", "G60890ZT", "G63628AV", "G64527OM", "G64973KT", "G65562ZE", "G66163OV", "G67381VP", "G70101JE", "G70375MX", "G70894RY", "G72735IY", "G74645FT", "G74722FL", "G77477NL", "G77582RK", "G78059CC", "G78790NZ", "G79568CQ", "G81006GJ", "G81295CK", "G82320NZ", "G86537AD", "G89186VO", "G91636VS", "G92289SP", "G95898GD", "G98719SR" ], "uniprot_id": "P08575" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Vascular endothelial and megakaryocytic tumors", "glycan_involvement": "Glycosylation modulates cell adhesion and antibody binding.", "mechanism": "CD31 marks endothelial cells and megakaryocytes, aiding diagnosis of vascular tumors.", "protein": "CD31 (PECAM-1)", "protein_enriched": { "function": "Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and ", "gene_name": "PECAM1", "glycan_count": 84, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G13131HA", "G27058EU", "G27947YN", "G29545VG", "G31852PQ", "G35541EV", "G37818NZ", "G40926MX", "G41071NU", "G44753VC", "G46503DX", "G48414YA", "G56784JY", "G57776ZS", "G57776ZU", "G59626AS", "G60033FS", "G62765YT", "G68490OW", "G70441OD", "G70619PT", "G72747WU", "G79666IR", "G80920RR", "G83460ZZ", "G83646BJ", "G86182NS", "G90659AW", "G99668VU", "G49108TO", "G01650EU", "G02815KT", "G04657PL", "G27126ED", "G28541PG", "G47644PP", "G63041LO", "G95865ZB", "G01160VV", "G03644CB", "G05962QB", "G28622IK", "G30221QT", "G30740WO", "G37881RL", "G38663NM", "G39471UU", "G43223CG", "G45395BF", "G50856PC", "G55132BD", "G60834IK", "G70232NH", "G80075MS", "G80669SJ", "G81124ET", "G86880BF", "G87123QX", "G90382BL", "G92135MA", "G93718GY", "G01485JJ", "G02886BB", "G15169WU", "G25079LO", "G09831WQ", "G11629QQ", "G22310AV", "G32788FZ", "G33791AF", "G36442WJ", "G47518TP", "G52527GH", "G65414LI", "G81637OR", "G86795LJ", "G99679NM" ], "uniprot_id": "P16284" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Hematopoietic stem cell neoplasms", "glycan_involvement": "Heavily glycosylated; glycan chains influence cell migration and antibody detection.", "mechanism": "CD34 is a marker for hematopoietic stem cells and vascular neoplasms.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Epithelial tumors", "glycan_involvement": "Altered glycosylation in tumors affects antigenicity and metastatic potential.", "mechanism": "CEA is overexpressed in epithelial tumors, especially carcinomas.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Vascular endothelial and megakaryocytic tumors", "glycan_involvement": "N-glycosylation critical for secretion and function.", "mechanism": "vWF is used to identify vascular origin in tumors.", "protein": "Factor VIII\u2013related antigen (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Thyroglobulin-producing tumors", "glycan_involvement": "Glycosylation required for proper folding and secretion.", "mechanism": "Thyroglobulin is a marker for thyroid follicular cell tumors.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Urothelial neoplasms", "glycan_involvement": "Glycosylation affects membrane localization and antibody recognition.", "mechanism": "Uroplakin III is specific for urothelial cells, used in diagnosis of bladder tumors.", "protein": "Uroplakin III", "protein_enriched": { "function": "Chaperone protein which promotes assembly of the 20S proteasome. May cooperate with PSMG1-PSMG2 heterodimers to orchestrate the correct assembly of proteasomes", "gene_name": "PSMG3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q9BT73" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Lymphoid tumors", "glycan_involvement": "N-glycosylation essential for secretion and antigen binding.", "mechanism": "IgM is used to identify B-cell lineage in lymphoid neoplasms.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "B-cell lymphoma", "glycan_involvement": "Glycosylation modulates surface expression and antibody binding.", "mechanism": "CD79a is a B-cell marker used in diagnosis of B-cell lymphomas.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Mast cell tumor", "glycan_involvement": "Glycosylation affects receptor function and antibody recognition.", "mechanism": "CD117 is expressed in mast cells and used to diagnose mast cell tumors.", "protein": "CD117 (c-Kit)", "relationship_type": "biomarker", "source_pmcid": "PMC7158337" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA binds sialic acid-containing glycans on host cell surface.", "mechanism": "HA mediates viral attachment to sialic acid on host cells, enabling entry and infection.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Newcastle Disease", "glycan_involvement": "HN recognizes sialylated glycans for viral entry.", "mechanism": "HN binds sialic acid on host cells, triggering F protein-mediated membrane fusion.", "protein": "Hemagglutinin-Neuraminidase (HN)", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Fusion process depends on glycoprotein conformational changes.", "mechanism": "F protein mediates fusion of viral and host membranes after HN binding.", "protein": "Fusion (F) protein", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "GP is a heavily glycosylated envelope protein; glycosylation affects immune evasion and entry.", "mechanism": "GP mediates viral entry via endocytosis and fusion after proteolytic priming.", "protein": "GP (Ebola virus)", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Herpes Simplex Virus Infection", "glycan_involvement": "Viral glycoproteins bind to heparan sulfate chains on host cells.", "mechanism": "HSV uses heparan sulfate proteoglycans for initial attachment to host cells.", "protein": "Heparan sulfate proteoglycan", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Epstein\u2013Barr Virus Infection", "glycan_involvement": "CD21 is a glycoprotein; glycosylation may influence binding.", "mechanism": "EBV gp350/220 binds CD21 on B cells for viral entry.", "protein": "CD21 (CR2)", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Rhinovirus Infection (Common Cold)", "glycan_involvement": "ICAM-1 is a glycoprotein; glycosylation may affect virus binding.", "mechanism": "Rhinovirus binds ICAM-1 on respiratory epithelial cells for entry.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Foot and Mouth Disease", "glycan_involvement": "Integrins are glycoproteins; glycosylation may modulate virus binding.", "mechanism": "FMDV uses integrins for cell entry; adaptation to cell culture can switch to heparan sulfate usage.", "protein": "Integrins (e.g., \u03b1v\u03b23, \u03b1v\u03b25)", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "medium", "disease": "Reovirus Infection", "glycan_involvement": "JAMs are glycoproteins; glycosylation may influence interaction.", "mechanism": "Reovirus binds JAMs for cell entry.", "protein": "Junctional Adhesion Molecules (JAMs)", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "high", "disease": "Rotavirus Gastroenteritis", "glycan_involvement": "Sialic acid residues are essential for viral binding.", "mechanism": "Rotavirus uses sialic acid-containing glycoproteins and integrins for attachment and entry.", "protein": "Sialic acid-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7158351" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may affect antigenicity and immune recognition.", "mechanism": "Minor constituent of myelin; possible immune target in MS lesion formation.", "protein": "Myelin-associated glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7158368" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation may modulate immune response.", "mechanism": "Minor CNS myelin constituent; implicated as a weak antigen in MS autoimmunity.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158368" }, { "confidence": "high", "disease": "Pelizaeus-Merzbacher disease", "glycan_involvement": "Glycosylation status may affect protein folding and stability.", "mechanism": "Mutations in PLP cause hereditary CNS demyelination.", "protein": "Proteolipid protein", "relationship_type": "causal", "source_pmcid": "PMC7158368" }, { "confidence": "medium", "disease": "Peripheral neuropathies", "glycan_involvement": "Glycosylation critical for adhesion and compaction.", "mechanism": "Major PNS myelin protein; mutations cause peripheral demyelinating diseases.", "protein": "Protein zero", "relationship_type": "causal", "source_pmcid": "PMC7158368" }, { "confidence": "medium", "disease": "Peripheral neuropathies", "glycan_involvement": "Glycosylation affects trafficking and stability.", "mechanism": "Minor PNS myelin constituent; mutations linked to Charcot-Marie-Tooth disease.", "protein": "Peripheral myelin protein 22", "relationship_type": "causal", "source_pmcid": "PMC7158368" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Not glycosylated; but interacts with glycoproteins in myelin.", "mechanism": "Major autoantigen in MS; molecular mimicry with pathogens may trigger autoimmunity.", "protein": "Myelin basic protein", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7158368" }, { "confidence": "high", "disease": "Neuromyelitis optica", "glycan_involvement": "Glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibody target in NMO; not myelin-related but a glycosylated channel protein.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "causal", "source_pmcid": "PMC7158368" }, { "confidence": "medium", "disease": "Drug resistance in lymphoma", "glycan_involvement": "Glycosylation is essential for P-glycoprotein folding and function.", "mechanism": "P-glycoprotein expression is associated with multidrug resistance in canine lymphoma.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7158371" }, { "confidence": "high", "disease": "B-cell lymphoma", "glycan_involvement": "Surface glycosylation affects antibody recognition.", "mechanism": "CD79a is a B-cell marker used for immunophenotyping and diagnosis of B-cell lymphoma.", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "high", "disease": "T-cell lymphoma", "glycan_involvement": "Surface glycosylation affects antibody recognition.", "mechanism": "CD3 is a T-cell marker used for immunophenotyping and diagnosis of T-cell lymphoma.", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "medium", "disease": "B-cell lymphoma", "glycan_involvement": "Glycosylation modulates ligand binding and immune recognition.", "mechanism": "CD21 is a B-cell marker used for immunophenotyping of B-cell lymphomas.", "protein": "CD21", "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "medium", "disease": "Cutaneous lymphoma", "glycan_involvement": "Glycosylation affects receptor function and antibody binding.", "mechanism": "CD4 is used to distinguish T-cell subtypes in cutaneous lymphoma (mainly in humans).", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "medium", "disease": "Cutaneous lymphoma", "glycan_involvement": "Glycosylation affects receptor function and antibody binding.", "mechanism": "CD8+ T cells are the predominant neoplastic cell in canine epitheliotropic cutaneous lymphoma.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "medium", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation may affect secretion and stability.", "mechanism": "PTHrP secreted by lymphoma cells causes paraneoplastic hypercalcemia.", "protein": "Parathyroid hormone\u2013related peptide (PTHrP)", "relationship_type": "causal", "source_pmcid": "PMC7158371" }, { "confidence": "high", "disease": "Monoclonal gammopathy", "glycan_involvement": "N-glycosylation critical for immunoglobulin structure and function.", "mechanism": "Aberrant immunoglobulin production by B-cell lymphomas leads to monoclonal gammopathy.", "protein": "Immunoglobulins", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7158371" }, { "confidence": "low", "disease": "Canine lymphoma", "glycan_involvement": "Highly glycosylated; glycan changes may reflect disease state.", "mechanism": "Altered serum levels observed in lymphoma; significance unclear.", "protein": "Alpha-1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "low", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation may affect detection and function.", "mechanism": "Altered serum levels observed in lymphoma; significance unclear.", "protein": "Alpha fetoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7158371" }, { "confidence": "medium", "disease": "Duchenne muscular dystrophy (DMD)", "glycan_involvement": "Likely altered glycosylation affects membrane stability and function.", "mechanism": "Abnormal glycoprotein structure in the plasmalemma leads to increased calcium influx and muscle cell necrosis.", "protein": "Plasmalemma (muscle plasma membrane)", "relationship_type": "causal", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Hirschsprung disease (HD)", "glycan_involvement": "Tubulin is a glycoprotein; glycosylation may affect antibody recognition.", "mechanism": "Tubulin immunoreactivity marks neuronal structures in affected gut regions.", "protein": "Tubulin", "protein_enriched": { "function": "Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the add", "gene_name": "TUBA1B", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P68363" }, "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Neuronal intestinal dysplasia", "glycan_involvement": "MBP glycosylation may influence its localization and detection.", "mechanism": "MBP immunoreactivity highlights myelinated fibers and glial cells in the deep plexus.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Hereditary motor and sensory neuropathy type I", "glycan_involvement": "Immunoglobulin glycosylation is essential for function and detection.", "mechanism": "Immunocytochemical demonstration of immunoglobulins in peripheral nerves.", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "low", "disease": "Hirschsprung disease (HD)", "glycan_involvement": "VIP is a glycoprotein; glycosylation may affect signaling.", "mechanism": "Aberrant VIPergic-cholinergic fibers found in mucosal lamina propria.", "protein": "VIPergic-cholinergic fibers", "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Coronavirus-induced demyelinating encephalomyelitis", "glycan_involvement": "Spike protein glycosylation critical for host cell entry.", "mechanism": "Viral glycoprotein mediates infection and demyelination.", "protein": "Coronavirus spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Paramyxovirus encephalitis", "glycan_involvement": "Glycosylation required for viral infectivity.", "mechanism": "Viral glycoprotein mediates neuroinvasion and pathology.", "protein": "Paramyxovirus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7159638" }, { "confidence": "low", "disease": "Senile dementia", "glycan_involvement": "Glycosylation enables neuronal uptake.", "mechanism": "Used as a tracer for neuronal uptake and axonal transport studies.", "protein": "Horseradish peroxidase", "protein_enriched": { "function": "Removal of H(2)O(2), oxidation of toxic reductants, biosynthesis and degradation of lignin, suberization, auxin catabolism, response to environmental stresses such as wounding, pathogen attack and oxi", "gene_name": "PRXC1A", "glycan_count": 0, "glycosylation_sites_count": 8, "glytoucan_ids": [], "uniprot_id": "P00433" }, "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "low", "disease": "Neuropathies (general)", "glycan_involvement": "Glycosylation may affect antibody binding.", "mechanism": "Monoclonal antibodies to intermediate filaments used in neuropathology.", "protein": "Intermediate filaments", "relationship_type": "biomarker", "source_pmcid": "PMC7159638" }, { "confidence": "medium", "disease": "Nerve cell culture models", "glycan_involvement": "Glycosylation essential for receptor recognition and uptake.", "mechanism": "Structural requirements for glycoprotein-mediated endocytosis studied in nerve cells.", "protein": "Receptor-mediated endocytosis glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7159638" }, { "confidence": "high", "disease": "Cryptococcosis", "glycan_involvement": "Capsule is a heteropolysaccharide; glycosylation critical for structure and function.", "mechanism": "Capsule provides resistance to desiccation and virulence, enabling infection and immune evasion.", "protein": "Cryptococcus capsular polysaccharide", "relationship_type": "causal", "source_pmcid": "PMC7161403" }, { "confidence": "high", "disease": "Cryptococcosis", "glycan_involvement": "Antigen is glycosylated; glycan moieties recognized by diagnostic assays.", "mechanism": "Capsular antigen detected in serum/CSF/vitreous fluid for diagnosis and monitoring.", "protein": "Cryptococcus capsular antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Histoplasmosis", "glycan_involvement": "Glycosylation of cell wall proteins essential for pathogenicity.", "mechanism": "Cell wall glycoproteins mediate host cell entry and immune evasion.", "protein": "Histoplasma capsulatum cell wall glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7161403" }, { "confidence": "high", "disease": "Histoplasmosis", "glycan_involvement": "Glycosylated antigen detected by immunoassays.", "mechanism": "Antigen detected in urine/serum/CSF for diagnosis and monitoring.", "protein": "Histoplasma capsulatum antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Coccidioidomycosis", "glycan_involvement": "Glycosylation required for spherule integrity and pathogenicity.", "mechanism": "Spherule wall glycoproteins facilitate host tissue invasion and immune modulation.", "protein": "Coccidioides spherule wall glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Blastomycosis", "glycan_involvement": "Glycosylation essential for cell wall function and virulence.", "mechanism": "Cell wall glycoproteins mediate host interaction and immune evasion.", "protein": "Blastomyces dermatitidis cell wall glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Blastomycosis", "glycan_involvement": "Glycosylated antigen recognized by diagnostic tests.", "mechanism": "Antigen detected in urine for diagnosis and monitoring.", "protein": "Blastomyces dermatitidis antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Sporotrichosis", "glycan_involvement": "Glycosylation required for dimorphism and pathogenicity.", "mechanism": "Cell wall glycoproteins enable yeast phase transition and host infection.", "protein": "Sporothrix schenckii cell wall glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Sporotrichosis", "glycan_involvement": "Glycosylated antigen visualized in cytology.", "mechanism": "Antigen detected in exudates for diagnosis.", "protein": "Sporothrix schenckii antigen", "relationship_type": "biomarker", "source_pmcid": "PMC7161403" }, { "confidence": "medium", "disease": "Cryptococcosis", "glycan_involvement": "Glycan structure influences drug efficacy and immune recognition.", "mechanism": "Capsule targeted by antifungal therapy and immune response.", "protein": "Cryptococcus capsular polysaccharide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7161403" }, { "confidence": "high", "disease": "Chronic liver disease (fibrosis/cirrhosis)", "glycan_involvement": "Hyaluronic acid is a glycosaminoglycan; its synthesis and degradation are regulated by glycosylation enzymes.", "mechanism": "Serum hyaluronic acid increases due to reduced hepatic clearance in liver fibrosis/cirrhosis.", "protein": "Hyaluronic acid (hyaluronan)", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "high", "disease": "M\u00e9soth\u00e9liome (pleural/abdominal)", "glycan_involvement": "Glycosylation regulates hyaluronan synthase activity and secretion.", "mechanism": "Tumor cells secrete hyaluronic acid, leading to elevated levels in pleural/ascitic fluid.", "protein": "Hyaluronic acid (hyaluronan)", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "high", "disease": "Nephrotic syndrome", "glycan_involvement": "Albumin glycosylation may affect renal filtration and loss.", "mechanism": "Loss of albumin in urine is a hallmark of nephrotic syndrome.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7161405" }, { "confidence": "high", "disease": "Cold agglutinin disease", "glycan_involvement": "IgM glycosylation affects antibody stability and complement activation.", "mechanism": "IgM autoantibodies agglutinate RBCs at low temperature, causing hemolytic anemia.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "Polyarthritis rheumatoid (RA)", "glycan_involvement": "Glycosylation regulates hyaluronan metabolism in synovial tissue.", "mechanism": "Serum hyaluronic acid is increased in RA due to joint inflammation and turnover.", "protein": "Hyaluronic acid (hyaluronan)", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "Ent\u00e9ropathies exsudatives", "glycan_involvement": "Glycosylation may affect albumin stability and GI loss.", "mechanism": "Loss of albumin via GI tract is a marker of exudative enteropathy.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "Chronic liver disease (fibrosis/cirrhosis)", "glycan_involvement": "N-glycosylation modulates alpha-2-macroglobulin function and clearance.", "mechanism": "Included in composite fibrosis scores (Fibrotest, Fibrom\u00e8tre, Hepascore).", "protein": "Alpha-2-macroglobulin", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "Chronic liver disease (fibrosis/cirrhosis)", "glycan_involvement": "N-glycosylation affects TIMP1 stability and activity.", "mechanism": "Part of ELF score for liver fibrosis assessment.", "protein": "Tissue Inhibitor of Metalloproteinase 1 (TIMP1)", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "M\u00e9soth\u00e9liome (pleural/abdominal)", "glycan_involvement": "CEA is highly glycosylated; glycan structures affect immunodetection.", "mechanism": "CEA may be elevated in pleural/ascitic fluid in mesothelioma.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7161405" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Glycosylation affects protein S function and renal loss.", "mechanism": "Loss of protein S in urine contributes to thrombosis risk in nephrotic syndrome.", "protein": "Protein S", "protein_enriched": { "function": "Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis", "gene_name": "PROS1", "glycan_count": 5, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G57321FI", "G43417UB", "G71142DF", "G00912UN", "G48414YA" ], "uniprot_id": "P07225" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7161405" }, { "confidence": "high", "disease": "Copper accumulation (hepatopathy)", "glycan_involvement": "Glycosylation is essential for ceruloplasmin stability and secretion.", "mechanism": "Ceruloplasmin mediates copper mobilization from hepatocytes; impaired synthesis or secretion leads to copper retention and hepatocyte injury.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Hepatic fibrosis", "glycan_involvement": "Glycosylation affects folding and secretion; misfolded glycoprotein accumulates.", "mechanism": "Deficiency or abnormal glycosylation of alpha-1-antitrypsin leads to accumulation in hepatocytes, causing fibrosis.", "protein": "Alpha-1-antitrypsin", "relationship_type": "causal", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Hypocoagulability", "glycan_involvement": "Glycosylation required for antithrombin function and plasma stability.", "mechanism": "Reduced synthesis in liver disease leads to decreased anticoagulant activity and increased risk of thrombosis.", "protein": "Antithrombin", "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation required for secretion and clotting function.", "mechanism": "Decreased fibrinogen synthesis in severe liver disease contributes to DIC.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Hepatic failure", "glycan_involvement": "Albumin is glycosylated; glycosylation affects stability and half-life.", "mechanism": "Low albumin levels reflect impaired hepatic synthetic function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "medium", "disease": "Hypocoagulability", "glycan_involvement": "Glycosylation required for secretion and activation.", "mechanism": "Reduced plasminogen synthesis impairs fibrinolysis in liver disease.", "protein": "Plasminogen", "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Chronic hepatitis", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Reduced synthesis in chronic hepatitis leads to prolonged clotting times.", "protein": "Coagulation Factor IX", "protein_enriched": { "function": "Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipid", "gene_name": "F9", "glycan_count": 37, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27608TI", "G50236GJ", "G70593HA", "G76163CP", "G96881BQ", "G10651WD", "G45637XA", "G70649KP", "G81006GJ", "G29068FM", "G43417UB", "G18717LR", "G74722FL", "G57321FI", "G10008NR", "G12743GW", "G12793SR", "G15016TE", "G15169WU", "G17827EU", "G28847IN", "G31639NG", "G32551IQ", "G38277AO", "G39595FH", "G47518TP", "G48414YA", "G52527GH", "G58489ZK", "G66088HZ", "G69834CE", "G74815GQ", "G79318PG", "G86904UH", "G87108ET", "G92975MH", "G98725UL" ], "uniprot_id": "P00740" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Glycosylation required for secretion and function.", "mechanism": "Impaired hepatic synthesis or clearance affects Factor VIII levels.", "protein": "Coagulation Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "high", "disease": "Hepatic failure", "glycan_involvement": "Glycosylation required for secretion and clotting activity.", "mechanism": "Reduced prothrombin synthesis leads to bleeding tendency.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "medium", "disease": "Malnutrition", "glycan_involvement": "Glycosylation affects stability and iron-binding capacity.", "mechanism": "Low transferrin reflects impaired protein synthesis in malnutrition and liver disease.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161409" }, { "confidence": "medium", "disease": "Respiratory failure", "glycan_involvement": "Glycosylation is required for ACE stability and function.", "mechanism": "ACE is an endocrine function of the lung; respiratory failure impairs ACE activity, affecting blood pressure regulation.", "protein": "Angiotensin-converting enzyme", "relationship_type": "causal", "source_pmcid": "PMC7161410" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation affects GGT secretion and serum stability.", "mechanism": "Elevated serum GGT indicates liver dysfunction secondary to hypoxia from respiratory disease.", "protein": "Gamma-glutamyl transpeptidase", "relationship_type": "biomarker", "source_pmcid": "PMC7161410" }, { "confidence": "medium", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation modulates ALP activity and half-life.", "mechanism": "Increased serum ALP is a marker of hypoxia-induced liver injury.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161410" }, { "confidence": "low", "disease": "Liver dysfunction", "glycan_involvement": "Glycosylation may affect enzyme secretion.", "mechanism": "Serum increase reflects hepatocellular damage due to hypoxia.", "protein": "Sorbitol (inositol) dehydrogenase", "relationship_type": "biomarker", "source_pmcid": "PMC7161410" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Minor N-glycosylation affects hemoglobin stability.", "mechanism": "Reduced or dysfunctional hemoglobin causes anemic hypoxia.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7161410" }, { "confidence": "low", "disease": "Hypoxemia", "glycan_involvement": "Glycosylation may influence hemoglobin structure.", "mechanism": "Altered hemoglobin (methemoglobin, carboxyhemoglobin) impairs oxygen transport.", "protein": "Hemoglobin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7161410" }, { "confidence": "high", "disease": "Anemia", "glycan_involvement": "N-glycosylation is essential for EPO bioactivity.", "mechanism": "EPO stimulates erythropoiesis as a compensatory response to hypoxia.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7161410" }, { "confidence": "low", "disease": "Pulmonary edema", "glycan_involvement": "Glycosylation required for ACE localization and function.", "mechanism": "ACE activity in lung endothelium regulates fluid balance; dysfunction may contribute to edema.", "protein": "Angiotensin-converting enzyme", "relationship_type": "causal", "source_pmcid": "PMC7161410" }, { "confidence": "low", "disease": "Hypoxemia", "glycan_involvement": "Glycosylation affects GGT serum levels.", "mechanism": "Elevated GGT reflects hypoxic injury to liver due to respiratory disease.", "protein": "Gamma-glutamyl transpeptidase", "relationship_type": "biomarker", "source_pmcid": "PMC7161410" }, { "confidence": "low", "disease": "Pulmonary edema", "glycan_involvement": "Glycosylation modulates ALP function.", "mechanism": "Increased ALP may indicate secondary hepatic congestion from pulmonary edema.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161410" }, { "confidence": "medium", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation affects serum half-life and immune modulation", "mechanism": "Serum levels altered in lymphoma; reflects inflammation/tumor burden", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7161412" }, { "confidence": "high", "disease": "Monoclonal gammopathy", "glycan_involvement": "Glycosylation critical for Ig structure and function", "mechanism": "Monoclonal Ig produced by neoplastic B-cells in lymphoma", "protein": "Immunoglobulin (Ig)", "relationship_type": "biomarker", "source_pmcid": "PMC7161412" }, { "confidence": "high", "disease": "Canine lymphoma", "glycan_involvement": "Surface glycosylation required for cell signaling and antibody recognition", "mechanism": "B-cell marker for immunophenotyping lymphoma", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7161412" }, { "confidence": "medium", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation modulates antibody binding", "mechanism": "B-cell marker; potential target for antibody therapy", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7161412" }, { "confidence": "high", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation required for TCR complex stability", "mechanism": "T-cell marker for immunophenotyping lymphoma", "protein": "CD3", "protein_enriched": { "function": "Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-medi", "gene_name": "CD3D", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G02815KT", "G27058EU", "G30248BL", "G31852PQ", "G41247ZX", "G45395BF", "G62765YT", "G80920RR", "G83460ZZ", "G92050GC" ], "uniprot_id": "P04234" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161412" }, { "confidence": "medium", "disease": "Drug resistance in lymphoma", "glycan_involvement": "N-glycosylation required for proper folding and function", "mechanism": "Overexpression leads to multidrug resistance in lymphoma cells", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7161412" }, { "confidence": "high", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation affects secretion and stability", "mechanism": "Secreted by lymphoma cells, causes hypercalcemia", "protein": "Parathyroid hormone\u2013related peptide (PTHrP)", "relationship_type": "causal", "source_pmcid": "PMC7161412" }, { "confidence": "medium", "disease": "Canine lymphoma", "glycan_involvement": "Glycosylation modulates immune recognition", "mechanism": "Serum CRP elevated in lymphoma; reflects inflammation", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7161412" }, { "confidence": "medium", "disease": "Paraneoplastic anemia", "glycan_involvement": "Glycosylation affects hemoglobin binding", "mechanism": "Serum haptoglobin altered in lymphoma-related anemia", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161412" }, { "confidence": "medium", "disease": "Canine lymphoma", "glycan_involvement": "N-glycosylation required for receptor binding", "mechanism": "VEGF upregulated in lymphoma, promotes angiogenesis", "protein": "VEGF", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7161412" }, { "confidence": "high", "disease": "Diffuse large B-cell lymphoma (DLBCL)", "glycan_involvement": "Surface glycosylation critical for antibody recognition", "mechanism": "CD79a is expressed on B-cell lymphomas and used for immunophenotyping", "protein": "CD79a", "protein_enriched": { "function": "Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the ", "gene_name": "CD79A", "glycan_count": 4, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G31852PQ", "G62765YT", "G64527OM", "G80920RR" ], "uniprot_id": "P11912" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "high", "disease": "Epitheliotropic cutaneous lymphoma (mycosis fungoides)", "glycan_involvement": "Glycosylation affects CD8 stability and function", "mechanism": "CD8+ T cells predominate in canine cutaneous lymphoma", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Epitheliotropic cutaneous lymphoma (mycosis fungoides)", "glycan_involvement": "Glycosylation modulates CD4 interactions", "mechanism": "CD4+ T cells predominate in human, but not canine, cutaneous lymphoma", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "high", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation required for secretion and stability", "mechanism": "PTHrP secreted by lymphoma cells induces hypercalcemia", "protein": "Parathyroid hormone\u2013related peptide (PTHrP)", "relationship_type": "causal", "source_pmcid": "PMC7161413" }, { "confidence": "high", "disease": "Monoclonal gammopathy", "glycan_involvement": "N-glycosylation affects immunoglobulin structure and detection", "mechanism": "Aberrant immunoglobulin production in B-cell lymphoma", "protein": "Immunoglobulins", "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Marginal zone lymphoma (MZL)", "glycan_involvement": "Glycosylation influences CD5 cell surface expression", "mechanism": "MZL cells are typically CD5-negative, aiding diagnosis", "protein": "CD5", "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Marginal zone lymphoma (MZL)", "glycan_involvement": "Glycosylation modulates CD10 function", "mechanism": "MZL cells are typically CD10-negative, distinguishing from other lymphomas", "protein": "CD10", "protein_enriched": { "function": "Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhi", "gene_name": "CD72", "glycan_count": 3, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02815KT", "G31852PQ", "G41247ZX" ], "uniprot_id": "P21854" }, "relationship_type": "biomarker", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation required for cytokine secretion", "mechanism": "IL-1 contributes to paraneoplastic hypercalcemia in lymphoma", "protein": "Interleukin-1 (IL-1)", "relationship_type": "causal", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and activity", "mechanism": "TNF-\u03b1 produced by lymphoma cells contributes to hypercalcemia", "protein": "Tumor necrosis factor-alpha (TNF-\u03b1)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct actio", "gene_name": "TNF", "glycan_count": 5, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00031MO", "G29931IJ", "G48818KL", "G56682BC", "G74722FL" ], "uniprot_id": "P01375" }, "relationship_type": "causal", "source_pmcid": "PMC7161413" }, { "confidence": "medium", "disease": "Hypercalcemia of malignancy", "glycan_involvement": "Glycosylation essential for TGF-\u03b2 maturation and function", "mechanism": "TGF-\u03b2 is implicated in paraneoplastic hypercalcemia", "protein": "Transforming growth factor-beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC7161413" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation modulates APP processing.", "mechanism": "Aberrant glycosylation of APP alters amyloid-beta production and aggregation.", "protein": "APP", "protein_enriched": { "function": "Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on", "gene_name": "App", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G41247ZX", "G49108TO" ], "uniprot_id": "P12023" }, "relationship_type": "causal", "source_pmcid": "PMC7166554" }, { "confidence": "high", "disease": "Schizophrenia", "glycan_involvement": "Polysialic acid chains are decreased.", "mechanism": "Reduced polysialylation of NCAM1 correlates with impaired synaptic plasticity.", "protein": "NCAM1", "relationship_type": "biomarker", "source_pmcid": "PMC7166554" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob disease", "glycan_involvement": "N-glycosylation sites modulate prion conversion.", "mechanism": "Altered glycosylation affects prion protein misfolding and aggregation.", "protein": "Prion protein (PrP)", "protein_enriched": { "function": "Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis t", "gene_name": "PRNP", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03636KD", "G57321FI", "G10256JP", "G25987BV", "G46687AB", "G49874UX", "G59937CP", "G62765YT", "G68490OW", "G80920RR", "G83460ZZ", "G88725PI", "G98611JV", "G49108TO" ], "uniprot_id": "P04156" }, "relationship_type": "causal", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "N-glycosylation pattern changes.", "mechanism": "Altered glycoforms of transferrin detected in CSF of MS patients.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Autism spectrum disorder", "glycan_involvement": "O-glycosylation required for function.", "mechanism": "Defective glycosylation impairs Reelin secretion and neuronal migration.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "N-glycosylation changes affect aggregation.", "mechanism": "Altered glycosylation of clusterin found in AD brain tissue.", "protein": "Clusterin", "protein_enriched": { "function": "Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922,", "gene_name": "CLU", "glycan_count": 295, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G02030ZB", "G03644CB", "G04657PL", "G04672QB", "G05724UK", "G05962QB", "G06110VR", "G06247RL", "G06356OH", "G07246CJ", "G08290VR", "G08918WF", "G10256JP", "G10486CT", "G10846ZT", "G11629QQ", "G11870QZ", "G11911BT", "G12313PD", "G12341GU", "G13694XX", "G14547CB", "G14972EH", "G15169WU", "G16125XL", "G17208MA", "G20312EM", "G22310AV", "G22625SJ", "G24835MQ", "G24954UD", "G25079LO", "G25418HZ", "G25451PN", "G26330YA", "G27058EU", "G27947YN", "G28622IK", "G30221QT", "G30740WO", "G31596VW", "G31986NC", "G32332VU", "G34989PA", "G37412TK", "G39188ZX", "G40574BA", "G40834TG", "G40926MX", "G41882MT", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45495MK", "G45526EA", "G46691LC", "G47448YK", "G47518TP", "G47737VJ", "G48414YA", "G49906RN", "G50757KG", "G50856PC", "G51413EV", "G51640FO", "G52527GH", "G54740VA", "G55383ZG", "G56518TU", "G56770VP", "G57776ZS", "G57888GL", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60834IK", "G60967DT", "G63381RX", "G64394MX", "G64527OM", "G65019XG", "G68490OW", "G69521XL", "G70101JE", "G70232NH", "G70418MS", "G70441OD", "G70619PT", "G70888PK", "G71146HJ", "G72667IM", "G72747WU", "G74724QE", "G75568BH", "G75983OB", "G76417NN", "G77582RK", "G78649WQ", "G78787DI", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82463GQ", "G82830MN", "G84225JN", "G84452RH", "G84862VB", "G86234IN", "G86795LJ", "G86880BF", "G87123QX", "G88374WZ", "G90382BL", "G91473PK", "G92081HT", "G92135MA", "G93718GY", "G94854LT", "G94917XT", "G99668VU", "G99679NM", "G04854VP", "G11115RO", "G20528HD", "G41071NU", "G42124LM", "G46503DX", "G53075ES", "G60033FS", "G60923RB", "G62765YT", "G63980BQ", "G83460ZZ", "G83633GK", "G94470IW", "G57321FI", "G01650EU", "G02815KT", "G08146BT", "G08293MJ", "G20425TQ", "G22140GZ", "G23863VK", "G37399XV", "G37818NZ", "G37868ZX", "G37881RL", "G42962KI", "G44215PV", "G45504EY", "G46687AB", "G50045TK", "G57776ZU", "G57818FI", "G61937QU", "G62837OZ", "G66163OV", "G72797UR", "G76295SF", "G77459ND", "G85144OK", "G90659AW", "G95865ZB", "G00406II", "G02528FI", "G02886BB", "G03382KH", "G05049YU", "G10819WX", "G22572EH", "G27126ED", "G27915IV", "G28096RS", "G28541PG", "G28681TP", "G31852PQ", "G35235RT", "G36003IU", "G39446WN", "G44211QA", "G47644PP", "G48584BU", "G49874UX", "G56284ZY", "G59924QI", "G63041LO", "G65184UU", "G70822IO", "G72197KC", "G74430RZ", "G75418YA", "G78790NZ", "G80479JV", "G82592ZH", "G83646BJ", "G85282JO", "G86752LQ", "G87661QW", "G92406TI", "G96577RX", "G98129XB", "G98611JV", "G01485JJ", "G02315DX", "G02628JF", "G03596YS", "G04784US", "G07755XJ", "G07810QS", "G08110WX", "G11314AS", "G13910DJ", "G14994KB", "G19972YZ", "G22589VJ", "G23719VF", "G24517ZG", "G26271XI", "G29545VG", "G29880MM", "G31118FR", "G31544HA", "G33791AF", "G34617SM", "G37509XX", "G38398KX", "G39595FH", "G39689FZ", "G41126SR", "G41247ZX", "G42358LZ", "G46823ME", "G47012YE", "G50427EO", "G52890YB", "G54010QB", "G54612UD", "G55412XP", "G57220OY", "G57317CE", "G59324HL", "G61256FT", "G62894KT", "G66760KM", "G66933CM", "G69834CE", "G71463BG", "G72735IY", "G72886NH", "G73918EY", "G78644BR", "G78811TO", "G79286RS", "G79635DB", "G80333GO", "G81128KB", "G82443XX", "G83229XP", "G83555HU", "G85269DF", "G85554PZ", "G86500WE", "G87051GH", "G87875QF", "G89827JR", "G91158SA", "G91636VS", "G92597CK", "G95177YH", "G95977AE", "G96416FQ", "G99966GV", "G49108TO", "G43417UB", "G24528MX", "G30970QQ", "G35541EV", "G37995HC", "G39619TI", "G64409MC", "G67506FN", "G70223PD", "G75607BQ", "G90093AU", "G93683YO", "G95678HJ" ], "uniprot_id": "P10909" }, "relationship_type": "biomarker", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "GPI-anchor glycosylation is essential.", "mechanism": "Aberrant glycosylation disrupts axonal connectivity.", "protein": "Contactin-2", "relationship_type": "causal", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Glioblastoma", "glycan_involvement": "N-glycosylation modulates adhesion.", "mechanism": "Altered glycosylation promotes tumor cell migration.", "protein": "L1CAM", "protein_enriched": { "function": "Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple proc", "gene_name": "L1CAM", "glycan_count": 58, "glycosylation_sites_count": 20, "glytoucan_ids": [ "G43769HG", "G41247ZX", "G57317CE", "G00912UN", "G04854VP", "G06247RL", "G06356OH", "G10486CT", "G27058EU", "G30740WO", "G37412TK", "G42124LM", "G43223CG", "G44215PV", "G49955PK", "G59626AS", "G62765YT", "G65184UU", "G70101JE", "G70619PT", "G72398FA", "G72790NZ", "G80920RR", "G83460ZZ", "G83646BJ", "G84452RH", "G86182NS", "G90659AW", "G94470IW", "G98611JV", "G46503DX", "G70232NH", "G31852PQ", "G45395BF", "G49108TO", "G10256JP", "G14260UH", "G23432EQ", "G64527OM", "G66621EA", "G66766XF", "G84820NF", "G02815KT", "G25451PN", "G34989PA", "G41071NU", "G60177UT", "G75983OB", "G76295SF", "G78790NZ", "G83229XP", "G01650EU", "G28541PG", "G36442WJ", "G37399XV", "G95865ZB", "G63980BQ", "G48414YA" ], "uniprot_id": "P32004" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7166554" }, { "confidence": "low", "disease": "Major depressive disorder", "glycan_involvement": "O-glycosylation pattern shifts.", "mechanism": "Glycosylation changes correlate with altered neuroimmune signaling.", "protein": "Glycodelin", "protein_enriched": { "function": "Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tiss", "gene_name": "PAEP", "glycan_count": 42, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G06110VR", "G06356OH", "G13290KJ", "G14696LD", "G23294PN", "G24835MQ", "G25837HW", "G27165KO", "G31916IQ", "G33671BL", "G33876UV", "G44339YF", "G46455GO", "G49874UX", "G51705EB", "G56749GV", "G66116BW", "G70418MS", "G72291OX", "G72667IM", "G75269BP", "G76012OT", "G76675AB", "G80858MF", "G81877PA", "G82463GQ", "G84452RH", "G86705PH", "G87889NL", "G92654OJ", "G93856AJ", "G02628JF", "G08110WX", "G22310AV", "G59821FL", "G60923RB", "G62765YT", "G81198YO", "G82592ZH", "G85228QD", "G87051GH", "G95977AE" ], "uniprot_id": "P09466" }, "relationship_type": "biomarker", "source_pmcid": "PMC7166554" }, { "confidence": "low", "disease": "Parkinson's disease", "glycan_involvement": "O-glycosylation affects filament assembly.", "mechanism": "Altered glycosylation of GFAP detected in PD patients.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC7166554" }, { "confidence": "medium", "disease": "Hepatitis C Virus infection", "glycan_involvement": "IFN-\u03bb4 is a glycoprotein; glycosylation may affect its secretion and function.", "mechanism": "Presence of functional IFN-\u03bb4 alleles in pDCs is associated with reduced IFN-\u03b1 induction upon HCV stimulation, potentially impacting antiviral response.", "protein": "IFN-\u03bb4", "protein_enriched": { "function": "Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeri", "gene_name": "IFNL1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8IU54" }, "relationship_type": "causal", "source_pmcid": "PMC7166754" }, { "confidence": "medium", "disease": "Hepatitis C Virus infection", "glycan_involvement": "IFN-\u03b1 is glycosylated, which is important for its stability and activity.", "mechanism": "Reduced induction of IFN-\u03b1 in pDCs with functional IFN-\u03bb4 alleles suggests impaired antiviral signaling.", "protein": "IFN-\u03b1", "protein_enriched": { "function": "Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase", "gene_name": "IFNA7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01567" }, "relationship_type": "biomarker", "source_pmcid": "PMC7166754" }, { "confidence": "medium", "disease": "Chronic Hepatitis", "glycan_involvement": "Glycosylation may modulate IFN-\u03bb4 secretion and receptor interaction.", "mechanism": "Functional IFN-\u03bb4 alleles are linked to impaired clearance of HCV, increasing risk of chronic hepatitis.", "protein": "IFN-\u03bb4", "protein_enriched": { "function": "Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeri", "gene_name": "IFNL1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q8IU54" }, "relationship_type": "causal", "source_pmcid": "PMC7166754" }, { "confidence": "high", "disease": "Systolic anterior motion of the mitral valve (SAM)", "glycan_involvement": "NT-proBNP is a glycoprotein; glycosylation affects its stability and clearance.", "mechanism": "NT-proBNP is elevated in cats with SAM, indicating myocardial stress due to outflow obstruction.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Systolic anterior motion of the mitral valve (SAM)", "glycan_involvement": "Troponin-I is glycosylated; glycosylation may affect its release and detection.", "mechanism": "Troponin-I is increased in some cats with SAM, suggesting myocardial injury.", "protein": "Troponin-I", "protein_enriched": { "function": "Involved in the binding of tRNA to the ribosomes", "gene_name": "rps10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19460" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "high", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation impacts NT-proBNP's half-life and immunoreactivity.", "mechanism": "NT-proBNP is used to detect myocardial stress in HCM.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation may modulate its serum levels.", "mechanism": "Troponin-I is a marker of myocardial injury in HCM.", "protein": "Troponin-I", "protein_enriched": { "function": "Involved in the binding of tRNA to the ribosomes", "gene_name": "rps10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19460" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Systolic anterior motion of the mitral valve (SAM)", "glycan_involvement": "Altered glycosylation may affect valve structure and function.", "mechanism": "Structural glycoprotein abnormalities in the mitral valve contribute to SAM.", "protein": "Mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7167033" }, { "confidence": "high", "disease": "Myxomatous mitral valve disease (MMVD)", "glycan_involvement": "Excessive glycosylation (proteoglycan accumulation) is central to pathology.", "mechanism": "Accumulation of glycoproteins in the valve matrix leads to myxomatous degeneration.", "protein": "Myxomatous mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation affects its diagnostic accuracy.", "mechanism": "NT-proBNP is elevated in DCM, reflecting cardiac stretch.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy (DCM)", "glycan_involvement": "Glycosylation may influence serum detection.", "mechanism": "Troponin-I is used to detect myocardial injury in DCM.", "protein": "Troponin-I", "protein_enriched": { "function": "Involved in the binding of tRNA to the ribosomes", "gene_name": "rps10", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P19460" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "medium", "disease": "Mitral regurgitation", "glycan_involvement": "Glycosylation modulates peptide stability.", "mechanism": "NT-proBNP increases with severity of mitral regurgitation, reflecting volume overload.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC7167033" }, { "confidence": "high", "disease": "Mitral regurgitation", "glycan_involvement": "Proteoglycan/glycoprotein accumulation disrupts valve architecture.", "mechanism": "Glycoprotein-rich myxomatous degeneration leads to valve incompetence and regurgitation.", "protein": "Myxomatous mitral valve glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7167033" }, { "confidence": "high", "disease": "Acute Myeloid Leukemia (AML)", "glycan_involvement": "CD33 is a sialic acid-binding glycoprotein; glycosylation affects antibody binding.", "mechanism": "CD33 is targeted by Gemtuzumab Ozogamicin for AML therapy.", "protein": "CD33", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7168573" }, { "confidence": "high", "disease": "Red Blood Cell Alloimmunization", "glycan_involvement": "Glycosylation defines antigenic epitopes recognized by antibodies.", "mechanism": "Alloimmunization occurs due to immune response against glycosylated RBC antigens after transfusion.", "protein": "Erythrocyte antigens (ABO, Rhesus, Kell, Duffy, Lutheran, Lewis, MNS)", "relationship_type": "causal", "source_pmcid": "PMC7168573" }, { "confidence": "high", "disease": "Von Willebrand Disease", "glycan_involvement": "Glycosylation modulates VWF multimerization and function.", "mechanism": "Deficiency or dysfunction of VWF leads to bleeding disorder.", "protein": "Von Willebrand factor", "relationship_type": "biomarker", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Acute Lymphoblastic Leukemia (ALL)", "glycan_involvement": "Fusion protein may alter glycosylation patterns affecting cell signaling.", "mechanism": "BCR/ABL positivity guides tyrosine kinase inhibitor therapy in ALL.", "protein": "BCR/ABL fusion protein", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7168573" }, { "confidence": "high", "disease": "Red Blood Cell Alloimmunization", "glycan_involvement": "Kell is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "Anti-K antibodies cause hemolytic transfusion reactions.", "protein": "K antigen (Kell)", "relationship_type": "causal", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Red Blood Cell Alloimmunization", "glycan_involvement": "Lea is a glycosylated antigen; glycan structure determines immunogenicity.", "mechanism": "Anti-Lea antibodies can cause transfusion reactions.", "protein": "Lea antigen", "relationship_type": "causal", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Red Blood Cell Alloimmunization", "glycan_involvement": "Fya is a glycosylated antigen; glycan structure is immunogenic.", "mechanism": "Anti-Fya antibodies can cause hemolytic reactions.", "protein": "Fya antigen", "relationship_type": "causal", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Red Blood Cell Alloimmunization", "glycan_involvement": "Lutheran antigens are glycoproteins; glycosylation affects antigenicity.", "mechanism": "Anti-Lu(a/b) antibodies can cause transfusion complications.", "protein": "Lu(a/b) antigens", "relationship_type": "causal", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Veno-Occlusive Disease (VOD)", "glycan_involvement": "CD33 glycosylation may affect GO binding and toxicity profile.", "mechanism": "GO exposure previously linked to increased VOD risk post-transplant, but current data show no significant association.", "protein": "Gemtuzumab Ozogamicin (GO) target: CD33", "relationship_type": "causal/risk factor", "source_pmcid": "PMC7168573" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation of RBC antigens drives immune response.", "mechanism": "Hemophilia A patients have highest rate of RBC alloimmunization due to frequent transfusions.", "protein": "Erythrocyte antigens (ABO, Rhesus, Kell, etc.)", "relationship_type": "biomarker/risk factor", "source_pmcid": "PMC7168573" }, { "confidence": "high", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation is essential for CD59 function and cell surface localization.", "mechanism": "CD59 inhibits complement membrane attack complex formation, protecting cells from immune-mediated lysis.", "protein": "CD59", "protein_enriched": { "function": "Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation (PubMed:11882685, PubMed:1698710, PubMed:2475111, PubMed:24", "gene_name": "CD59", "glycan_count": 226, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G51287LK", "G60554YG", "G74724QE", "G31685JQ", "G12728EY", "G22625SJ", "G47448YK", "G49108TO", "G00176HZ", "G00273SJ", "G00912UN", "G02030ZB", "G02315DX", "G02528FI", "G02815KT", "G03382KH", "G04657PL", "G05962QB", "G06247RL", "G06290IR", "G06330RB", "G06356OH", "G07246CJ", "G07483YN", "G07755XJ", "G08520NM", "G08918WF", "G09831WQ", "G10846ZT", "G11629QQ", "G12341GU", "G12793SR", "G13131HA", "G13191RB", "G13728QT", "G13749ZZ", "G14456RI", "G14882EB", "G14972EH", "G14994KB", "G15169WU", "G15488CF", "G16768LX", "G16828VN", "G17208MA", "G18647XP", "G20312EM", "G22310AV", "G22768VO", "G23133OF", "G23863VK", "G23984SE", "G24835MQ", "G24954UD", "G25418HZ", "G27058EU", "G27126ED", "G27919IH", "G29501UT", "G30740WO", "G30751OD", "G30799SW", "G31596VW", "G31615DN", "G31852PQ", "G32788FZ", "G34617SM", "G34989PA", "G36013ES", "G36134VO", "G36191CD", "G36379GD", "G37412TK", "G37773JL", "G37818NZ", "G39064KU", "G39213VZ", "G39595FH", "G40124HY", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41405QQ", "G42124LM", "G43223CG", "G43669FQ", "G44173IH", "G44215PV", "G44413JJ", "G44778BV", "G45395BF", "G45883VE", "G46487SG", "G46665ZP", "G46691LC", "G46902YN", "G47012YE", "G47518TP", "G47644PP", "G48414YA", "G50120TH", "G50427EO", "G50856PC", "G51413EV", "G52114WE", "G52358QA", "G52589SM", "G55220VL", "G56087PR", "G56518TU", "G57557NS", "G57776ZS", "G57888GL", "G57939IT", "G58596DI", "G58598BO", "G58667NI", "G59536GA", "G59626AS", "G59924QI", "G60033FS", "G60177UT", "G60834IK", "G61207RZ", "G61256FT", "G61505ZR", "G61806WR", "G62765YT", "G63628AV", "G63640QH", "G63889NK", "G64227LK", "G64394MX", "G64527OM", "G65019XG", "G65092SV", "G66621EA", "G66760KM", "G67164EE", "G67900CJ", "G68833MP", "G69521XL", "G70232NH", "G70619PT", "G70822IO", "G70888PK", "G70894RY", "G71146HJ", "G71463BG", "G71919QK", "G72667IM", "G72797UR", "G72886NH", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76417NN", "G77023TY", "G77149EE", "G77669RF", "G78059CC", "G78502KD", "G78649WQ", "G79568CQ", "G79666IR", "G80075MS", "G80223IX", "G80858MF", "G80920RR", "G80966KZ", "G81124ET", "G81198YO", "G81263BG", "G81637OR", "G82348BZ", "G82443XX", "G82830MN", "G83229XP", "G83633GK", "G83646BJ", "G84452RH", "G85269DF", "G85282JO", "G85737WG", "G86182NS", "G86226EA", "G86234IN", "G86357DX", "G86408JD", "G86795LJ", "G86880BF", "G87123QX", "G87618BG", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G90717TP", "G91473PK", "G91636VS", "G92062TF", "G92081HT", "G92135MA", "G92275SC", "G93141AZ", "G93993PD", "G94470IW", "G94831VI", "G95177YH", "G95865ZB", "G95977AE", "G98611JV", "G57321FI", "G01079KY", "G16389EC", "G31544HA", "G46687AB", "G50045TK", "G51519NL", "G71269BI", "G75727PF", "G80218BM", "G83461WR", "G90093AU" ], "uniprot_id": "P13987" }, "relationship_type": "protective", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Degenerative disease", "glycan_involvement": "Glycosylation modulates fibronectin's binding to integrins and ECM.", "mechanism": "Altered fibronectin-mediated cell-ECM interactions contribute to tissue degeneration.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Parvoviral enteritis", "glycan_involvement": "Notch receptor glycosylation regulates ligand binding and signaling.", "mechanism": "Disruption of Notch signaling by enterocyte loss impairs intestinal regeneration.", "protein": "Notch receptor", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "high", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation affects light chain solubility and aggregation.", "mechanism": "Misfolded light chains aggregate as amyloid deposits in tissues.", "protein": "Immunoglobulin light chains", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "high", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation influences amyloid A stability and deposition.", "mechanism": "Chronic inflammation increases serum amyloid A, leading to amyloid deposition.", "protein": "Amyloid A protein", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Neoplasia", "glycan_involvement": "Integrin glycosylation modulates ligand binding and signaling.", "mechanism": "Altered integrin-mediated adhesion promotes tumor invasion and metastasis.", "protein": "Integrins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7171462" }, { "confidence": "high", "disease": "Infectious disease", "glycan_involvement": "Glycosylation determines receptor-pathogen interactions.", "mechanism": "Pathogens exploit glycoprotein receptors for cell entry.", "protein": "Transmembrane glycoprotein receptors", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Autoimmune disease", "glycan_involvement": "Glycosylation is required for complement protein stability and function.", "mechanism": "Unregulated complement activation damages host cells.", "protein": "Complement components (C5, C6, C7, C8, C9)", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Immunodeficiency", "glycan_involvement": "Glycosylation is critical for CD protein folding and surface expression.", "mechanism": "Defective CD proteins impair immune cell signaling.", "protein": "Cluster of Differentiation proteins (e.g., CD3)", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation affects aggregation propensity.", "mechanism": "AL protein aggregates form amyloid deposits in tissues.", "protein": "Amyloid protein AL", "relationship_type": "causal", "source_pmcid": "PMC7171462" }, { "confidence": "high", "disease": "Gastritis", "glycan_involvement": "CagA is a glycoprotein; glycosylation may affect host interaction.", "mechanism": "CagA is injected into host cells, deregulates signaling, initiates pathogenesis.", "protein": "CagA", "protein_enriched": { "function": "May be necessary for the transcription, folding, export, or function of the cytotoxin", "gene_name": "cagA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55980" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "high", "disease": "Peptic ulcer", "glycan_involvement": "Glycosylation may modulate CagA-host interactions.", "mechanism": "CagA-positive H. pylori strains are associated with increased risk of peptic ulcer.", "protein": "CagA", "protein_enriched": { "function": "May be necessary for the transcription, folding, export, or function of the cytotoxin", "gene_name": "cagA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55980" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "high", "disease": "Gastritis", "glycan_involvement": "BabA2 binds host glycans; glycosylation critical for adhesion.", "mechanism": "BabA2 mediates H. pylori adhesion to gastric mucosa via Lewis b antigens.", "protein": "BabA2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O25831" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "medium", "disease": "Gastritis", "glycan_involvement": "Glycosylation may affect toxin activity and cell targeting.", "mechanism": "VacA toxin induces vacuolation in gastric epithelial cells.", "protein": "VacA", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P56112" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "Glycosylation may influence CagA stability and host signaling.", "mechanism": "CagA-positive strains increase risk of gastric cancer via chronic inflammation.", "protein": "CagA", "protein_enriched": { "function": "May be necessary for the transcription, folding, export, or function of the cytotoxin", "gene_name": "cagA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55980" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "high", "disease": "Antibiotic-resistant H. pylori infection", "glycan_involvement": "Glycan structures block bacterial glycoprotein-host interactions.", "mechanism": "Cranberry glycan-rich fraction inhibits H. pylori adhesion to gastric cells.", "protein": "High-molecular-weight cranberry constituent", "relationship_type": "protective", "source_pmcid": "PMC7172567" }, { "confidence": "medium", "disease": "Cystic fibrosis lung infection", "glycan_involvement": "O-antigen is a glycoprotein; glycosylation determines serotype.", "mechanism": "O-serotype variation used to type P. aeruginosa strains in CF patients.", "protein": "O-antigen (P. aeruginosa O-serotype)", "relationship_type": "biomarker", "source_pmcid": "PMC7172567" }, { "confidence": "medium", "disease": "Chronic P. aeruginosa infection", "glycan_involvement": "Glycosylation may affect enzyme secretion and activity.", "mechanism": "Elastase production correlates with virulence in chronic infection.", "protein": "Elastase", "protein_enriched": { "function": "Cleaves host elastin, collagen, IgG, and several complement components as well as endogenous pro-aminopeptidase (PubMed:11533066). Autocatalyses processing of its pro-peptide (PubMed:1744034, PubMed:9", "gene_name": "lasB", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14756" }, "relationship_type": "biomarker", "source_pmcid": "PMC7172567" }, { "confidence": "medium", "disease": "Atrophic gastritis", "glycan_involvement": "Glycosylation may modulate immune evasion.", "mechanism": "Presence of intact cag island reduces therapy efficacy, possibly via immunosuppression.", "protein": "Cag Pathogenicity Island proteins", "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "medium", "disease": "Gastroduodenal ulcer", "glycan_involvement": "Binds host glycan structures; glycosylation essential for function.", "mechanism": "BabA2-mediated adhesion facilitates colonization and ulcer formation.", "protein": "BabA2", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O25831" }, "relationship_type": "causal", "source_pmcid": "PMC7172567" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects serum detection and tumor specificity.", "mechanism": "AFP is produced by fetal liver and certain tumors; elevated in HCC.", "protein": "Alpha fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Yolk sac tumor", "glycan_involvement": "Glycosylation patterns may distinguish tumor origin.", "mechanism": "AFP is secreted by yolk sac tumors; used for diagnosis.", "protein": "Alpha fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency", "glycan_involvement": "Glycosylation affects folding and secretion.", "mechanism": "AAT accumulates in hepatocytes due to misfolding; deficiency causes liver disease.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Adenocarcinoma (ovary, colon, breast)", "glycan_involvement": "Sialylation and O-glycosylation are key for antigenicity.", "mechanism": "TAG-72 is overexpressed in adenocarcinomas.", "protein": "Tumor-associated glycoprotein 72 (TAG-72, CA 72-4)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Adenocarcinoma", "glycan_involvement": "Glycosylation modulates antibody recognition.", "mechanism": "Ber-EP4 is expressed on most epithelial tumors.", "protein": "Ber-EP4 (Ep-CAM)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Ovarian carcinoma", "glycan_involvement": "Heavily O-glycosylated mucin-type glycoprotein.", "mechanism": "CA125 is elevated in ovarian carcinoma; used for monitoring.", "protein": "CA125 (OC125)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Pancreatic carcinoma", "glycan_involvement": "Sialyl Lewis a glycan is the antigenic determinant.", "mechanism": "CA19-9 is elevated in pancreatic and GI cancers.", "protein": "CA19-9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Adenocarcinoma", "glycan_involvement": "Altered O-glycosylation in tumors increases immunoreactivity.", "mechanism": "EMA is overexpressed in carcinomas.", "protein": "Epithelial membrane antigen (EMA, MUC1)", "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Neuroendocrine tumors", "glycan_involvement": "Glycosylation affects secretion and detection.", "mechanism": "Chromogranin A is present in neuroendocrine granules.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Acute leukemia", "glycan_involvement": "N-glycosylation required for cell surface expression.", "mechanism": "CD34 marks hematopoietic progenitors; used in leukemia diagnosis.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC7173451" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Extensive N-glycosylation of N-terminal region shields neutralizing epitopes, reducing antibody effectiveness.", "mechanism": "GP5 is a major envelope glycoprotein expressing neutralization determinants; involved in virus entry and immune evasion.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Lactate dehydrogenase-elevating virus infection", "glycan_involvement": "N-glycosylation of N-terminal region; strains lacking glycosylation are more susceptible to neutralization and do not persist.", "mechanism": "GP5 glycosylation reduces immunogenicity, enabling persistent infection by blocking neutralizing antibody access.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "medium", "disease": "Equine viral arteritis", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "GP5 expresses major neutralization determinants; involved in virus entry and immune response.", "protein": "GP5", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Equine viral arteritis", "glycan_involvement": "Glycosylation likely affects receptor binding and tropism.", "mechanism": "Heterotrimer of minor envelope glycoproteins mediates cell tropism and receptor binding, determining host range.", "protein": "GP2/GP3/GP4 heterotrimer", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Marked variation in glycosylation among field strains impacts neutralization and immune response.", "mechanism": "These glycoproteins induce neutralizing antibodies; variation in glycosylation affects vaccine efficacy.", "protein": "GP3/GP4/GP5", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173463" }, { "confidence": "medium", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "M is nonglycosylated but modulates glycoprotein function.", "mechanism": "M protein forms heterodimer with GP5 and influences GP5 conformation and immune recognition.", "protein": "M", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173463" }, { "confidence": "medium", "disease": "Gill-associated virus disease (GAV)", "glycan_involvement": "Cleavage from polyprotein precursor; glycosylation likely important for function.", "mechanism": "gp116 is a major envelope glycoprotein spike involved in virus entry in crustaceans.", "protein": "gp116", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "medium", "disease": "Gill-associated virus disease (GAV)", "glycan_involvement": "Cleavage from polyprotein precursor; glycosylation likely important for function.", "mechanism": "gp64 is a minor envelope glycoprotein spike involved in virus entry.", "protein": "gp64", "relationship_type": "causal", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Porcine reproductive and respiratory syndrome (PRRS)", "glycan_involvement": "Glycan shielding delays neutralizing antibody response.", "mechanism": "Neutralizing antibodies against GP5 correlate with virus clearance and protection.", "protein": "GP5", "relationship_type": "protective", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Lactate dehydrogenase-elevating virus infection", "glycan_involvement": "Loss of glycosylation leads to neurovirulence and loss of persistence.", "mechanism": "Glycosylation status of GP5 determines persistence and neurovirulence in mice.", "protein": "GP5", "relationship_type": "biomarker", "source_pmcid": "PMC7173463" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "N-glycosylation required for proper folding and autocleavage; tissue-specific glycosylation patterns.", "mechanism": "Elevated serum GGT activity is detected in liver disease due to increased expression/release.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "biomarker", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Pancreatic disease", "glycan_involvement": "N-glycosylation required for function and stability.", "mechanism": "Elevated GGT in serum is associated with pancreatic disease, including cancer and inflammation.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "biomarker", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Cancer (various, including hepatocellular carcinoma)", "glycan_involvement": "N-glycosylation required for folding; altered glycosylation may affect tumor biology.", "mechanism": "GGT is upregulated in tumors and preneoplastic foci; contributes to chemotherapy resistance.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Chemotherapy resistance", "glycan_involvement": "N-glycosylation required for enzyme activity.", "mechanism": "GGT expression in tumors increases resistance to chemotherapeutic agents.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "causal", "source_pmcid": "PMC7173497" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "N-glycosylation required for enzyme function.", "mechanism": "GGT inhibitors reduce asthma symptoms in animal models.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173497" }, { "confidence": "medium", "disease": "Reperfusion injury", "glycan_involvement": "N-glycosylation required for enzyme function.", "mechanism": "GGT inhibition is protective in animal models of reperfusion injury.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Cysteine deficiency", "glycan_involvement": "N-glycosylation required for folding and autocleavage.", "mechanism": "GGT knockout mice develop cysteine deficiency due to impaired GSH breakdown and cysteine salvage.", "protein": "\u03b3-Glutamyltransferase (GGT, GGT1)", "relationship_type": "causal", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Viral infection (coronavirus, others)", "glycan_involvement": "N-glycosylation critical for folding and function; 11 glycosylation sites.", "mechanism": "APN serves as a receptor for coronaviruses and other viruses, facilitating infection.", "protein": "Aminopeptidase N (APN/CD13)", "relationship_type": "causal", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "Nephrotoxicity", "glycan_involvement": "Not glycosylated; not applicable.", "mechanism": "GSTs catalyze detoxification of electrophilic xenobiotics, reducing nephrotoxic risk.", "protein": "Glutathione S-transferases (GSTs)", "relationship_type": "protective", "source_pmcid": "PMC7173497" }, { "confidence": "medium", "disease": "Nephrotoxicity", "glycan_involvement": "Rat enzyme is glycosylated; human enzyme is not.", "mechanism": "Hydrolyzes cysteinylglycine S-conjugates; altered activity affects nephrotoxicant metabolism.", "protein": "Cysteinylglycine dipeptidase (Renal dipeptidase, DPEP1)", "protein_enriched": { "function": "Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4 (PubMed:2303490, PubMed:31442408, PubMed:32325220, PubMed:6334084). Hydrolyzes cystinyl-bis-glycine (", "gene_name": "DPEP1", "glycan_count": 141, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G04657PL", "G05049YU", "G07246CJ", "G07755XJ", "G08918WF", "G10486CT", "G10819WX", "G12341GU", "G13131HA", "G14972EH", "G16125XL", "G18647XP", "G20528HD", "G24528MX", "G27058EU", "G27915IV", "G27947YN", "G29299MO", "G35541EV", "G37399XV", "G40926MX", "G41071NU", "G42124LM", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G46503DX", "G49755GI", "G49906RN", "G57776ZS", "G59626AS", "G60033FS", "G60834IK", "G62765YT", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72787SB", "G72790NZ", "G79666IR", "G80075MS", "G80479JV", "G80920RR", "G83460ZZ", "G83646BJ", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87661QW", "G89045VA", "G89827JR", "G90659AW", "G92135MA", "G01160VV", "G02815KT", "G03644CB", "G12745LE", "G15127JD", "G28622IK", "G29545VG", "G30221QT", "G30740WO", "G31852PQ", "G32788FZ", "G37509XX", "G39471UU", "G45504EY", "G50045TK", "G51653BI", "G55132BD", "G56518TU", "G60967DT", "G70232NH", "G70375MX", "G71463BG", "G77547TA", "G78649WQ", "G80669SJ", "G81124ET", "G82443XX", "G87123QX", "G90382BL", "G94665LC", "G98611JV", "G01485JJ", "G02528FI", "G05962QB", "G17208MA", "G27126ED", "G33416PL", "G36442WJ", "G37692EO", "G37818NZ", "G37995HC", "G40834TG", "G44753VC", "G45526EA", "G46691LC", "G49589RB", "G50856PC", "G58954YZ", "G59324HL", "G65414LI", "G70223PD", "G75568BH", "G76295SF", "G84225JN", "G93718GY", "G95046LV", "G99668VU", "G99679NM", "G43417UB", "G06247RL", "G07810QS", "G10488MI", "G23719VF", "G28541PG", "G35029YA", "G35253PZ", "G36379GD", "G37412TK", "G39446WN", "G40206WX", "G41840AI", "G47702MW", "G53075ES", "G58087IP", "G61256FT", "G63040RU", "G77669RF", "G78787DI", "G87389XI", "G49108TO" ], "uniprot_id": "P16444" }, "relationship_type": "causal/protective", "source_pmcid": "PMC7173497" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CD4 is a glycoprotein; glycosylation affects HIV binding.", "mechanism": "CD4 acts as the primary receptor for HIV-1 entry into host cells.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CCR5 is glycosylated, which modulates HIV gp120 binding.", "mechanism": "CCR5 serves as a coreceptor for HIV-1 entry; blocking CCR5 prevents infection.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CXCR4 glycosylation influences HIV tropism.", "mechanism": "CXCR4 is an alternative coreceptor for HIV-1 entry.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "HIV/AIDS, Herpes simplex virus infection", "glycan_involvement": "Glycosylation of viral envelope proteins is essential for receptor binding and immune evasion.", "mechanism": "Viral glycoproteins mediate attachment and entry into host cells via glycoprotein-receptor interactions.", "protein": "Viral envelope glycoproteins (e.g., HIV gp120, HSV glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Acts on host glycoprotein glycans (sialic acid).", "mechanism": "Neuraminidase cleaves terminal sialic acid from host glycoproteins, enabling viral release.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "Multiple viral infections (e.g., HIV, HSV, Influenza)", "glycan_involvement": "Glycosylation determines receptor specificity and viral tropism.", "mechanism": "Serve as viral entry points; targeted by viral glycoproteins.", "protein": "Host cell surface glycoprotein receptors", "relationship_type": "causal", "source_pmcid": "PMC7173505" }, { "confidence": "medium", "disease": "HIV/AIDS, other viral infections", "glycan_involvement": "Lectin-glycan interactions are critical for viral attachment.", "mechanism": "Lectin receptors on host cells mediate viral entry; targeted by glycan-modified nanoparticles.", "protein": "Lectin receptors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "medium", "disease": "Cytomegalovirus infection (CMV)", "glycan_involvement": "UL97 is a viral kinase; glycosylation status not specified.", "mechanism": "UL97 phosphorylates ganciclovir, activating it against CMV.", "protein": "UL97", "protein_enriched": { "function": "", "gene_name": "UL4", "glycan_count": 0, "glycosylation_sites_count": 9, "glytoucan_ids": [], "uniprot_id": "Q6SWC6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "medium", "disease": "Herpes simplex virus infection (HSV-1, HSV-2), Varicella-Zoster virus infection (VZV)", "glycan_involvement": "Enzyme may be glycosylated; glycan role not detailed.", "mechanism": "Phosphorylates acyclovir, enabling selective antiviral activity.", "protein": "Viral thymidine kinase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "medium", "disease": "Hepatitis B virus infection (HBV), Hepatitis C virus infection (HCV), Human papillomavirus infection (HPV)", "glycan_involvement": "Interferon-\u03b1 is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Interferon-\u03b1 inhibits viral protein synthesis and replication.", "protein": "Interferon-\u03b1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173505" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Binds specific sialylated glycans on host cells", "mechanism": "Mediates viral attachment to host sialic acids, determining host and tissue tropism", "protein": "Hemagglutinin (Influenza virus)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Enzymatic activity on sialylated glycans", "mechanism": "Cleaves sialic acids to release new virions from host cells", "protein": "Neuraminidase (Influenza virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition", "mechanism": "Mediates viral attachment to CD4 and chemokine receptors on T cells", "protein": "gp120 (HIV-1)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Pneumococcal pneumonia", "glycan_involvement": "Polysaccharide capsule is a glycan structure", "mechanism": "Prevents complement-mediated opsonization and phagocytosis", "protein": "Capsular polysaccharide (Streptococcus pneumoniae)", "relationship_type": "protective", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Meningococcal meningitis", "glycan_involvement": "Polysaccharide capsule is a glycan structure", "mechanism": "Inhibits complement activation and phagocytosis", "protein": "Capsular polysaccharide (Neisseria meningitidis)", "relationship_type": "protective", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Haemophilus influenzae type b disease", "glycan_involvement": "Polysaccharide capsule is a glycan structure", "mechanism": "Prevents immune clearance by host", "protein": "Capsular polysaccharide (Haemophilus influenzae)", "relationship_type": "protective", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Sepsis (Gram-negative)", "glycan_involvement": "O-antigen polysaccharide and core oligosaccharide are glycan components", "mechanism": "Lipid A triggers TLR4-mediated inflammation; polysaccharide chains inhibit complement", "protein": "Lipopolysaccharide (LPS, Gram-negative bacteria)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation required for function and immune evasion", "mechanism": "Mediates viral attachment and entry into host neurons", "protein": "Glycoprotein (Rabies virus)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "medium", "disease": "Herpesvirus infections", "glycan_involvement": "Glycosylation modulates immune recognition and tropism", "mechanism": "Mediates viral entry and cell-to-cell spread", "protein": "Glycoprotein (Herpesvirus)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects infectivity and immune evasion", "mechanism": "Envelope glycoproteins mediate viral entry into hepatocytes", "protein": "Glycoprotein (Hepatitis B virus)", "relationship_type": "causal", "source_pmcid": "PMC7173513" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Mediates viral entry and cell fusion, essential for RSV infectivity in bronchiolar epithelium.", "protein": "RSV Fusion Glycoprotein (F protein)", "relationship_type": "causal", "source_pmcid": "PMC7173523" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Heavily glycosylated; glycan structures affect host cell binding and immune recognition.", "mechanism": "Facilitates viral attachment to host cells, contributing to infection.", "protein": "RSV Attachment Glycoprotein (G protein)", "relationship_type": "causal", "source_pmcid": "PMC7173523" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation influences antibody binding and neutralization.", "mechanism": "Targeted by monoclonal antibody palivizumab for prophylaxis.", "protein": "RSV Fusion Glycoprotein (F protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173523" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "IgG glycosylation affects effector function and half-life.", "mechanism": "High serum IgG against RSV F protein ameliorates disease severity.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7173523" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "IgE glycosylation modulates receptor binding and immune activation.", "mechanism": "Virus-specific IgE may mediate hypersensitivity responses and severe obstructive illness.", "protein": "IgE", "relationship_type": "biomarker", "source_pmcid": "PMC7173523" }, { "confidence": "high", "disease": "Bronchiolitis", "glycan_involvement": "Antibody glycosylation affects pharmacokinetics and effector function.", "mechanism": "Binds RSV F glycoprotein, preventing infection and reducing hospitalization risk.", "protein": "Palivizumab (anti-RSV F monoclonal antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173523" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation impacts immunogenicity and vaccine efficacy.", "mechanism": "Purified F protein used in vaccine development to elicit protective immunity.", "protein": "RSV F protein (vaccine candidate)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173523" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation modulates host cell interaction and immune evasion.", "mechanism": "Mediates viral attachment and release, contributing to airway infection.", "protein": "Parainfluenza Virus Hemagglutinin-Neuraminidase Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7173523" }, { "confidence": "medium", "disease": "Bronchiolitis", "glycan_involvement": "Glycosylation affects receptor binding and antigenicity.", "mechanism": "Facilitates viral entry in rare cases of bronchiolitis.", "protein": "Influenza Virus Hemagglutinin Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7173523" }, { "confidence": "medium", "disease": "Bronchiolitis Obliterans", "glycan_involvement": "Glycosylation influences tropism and immune response.", "mechanism": "Associated with severe bronchiolitis obliterans via epithelial cell necrosis.", "protein": "Adenovirus Fiber Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7173523" }, { "confidence": "high", "disease": "HIV-1-associated dementia", "glycan_involvement": "gp120 glycosylation mediates receptor binding and immune evasion.", "mechanism": "gp120 interacts with neuronal chemokine receptors and NMDA receptor, inducing neuronal injury and apoptosis.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "high", "disease": "West Nile virus encephalitis", "glycan_involvement": "CCR5 is a glycoprotein; glycosylation affects receptor function and ligand binding.", "mechanism": "CCR5 mediates leukocyte trafficking to CNS, limiting viral burden and mortality.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "protective", "source_pmcid": "PMC7173529" }, { "confidence": "high", "disease": "HIV-1-associated dementia", "glycan_involvement": "CCR5 glycosylation modulates HIV-1 gp120 binding.", "mechanism": "CCR5 acts as a coreceptor for HIV-1 entry into glial cells; blocking CCR5 reduces HIV infection but may increase WNV risk.", "protein": "CCR5", "protein_enriched": { "function": "Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May p", "gene_name": "CCR5", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P51681" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "HIV-1-associated dementia", "glycan_involvement": "CXCR4 glycosylation influences ligand and gp120 binding.", "mechanism": "CXCR4 is a coreceptor for HIV-1 entry; elevated in HIV-infected CNS, may contribute to neuropathogenesis.", "protein": "CXCR4", "protein_enriched": { "function": "Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:249", "gene_name": "CXCR4", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P61073" }, "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "high", "disease": "HIV encephalitis", "glycan_involvement": "CD14 is a glycoprotein; glycosylation required for membrane localization and function.", "mechanism": "CD14+ monocytes carry HIV-1 across BBB, seeding infection in perivascular macrophages.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "HIV encephalitis", "glycan_involvement": "TLR4 glycosylation is essential for ligand recognition and signaling.", "mechanism": "TLR4 activation in microglia/astrocytes amplifies inflammatory response to HIV infection.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "Multiple sclerosis (model)", "glycan_involvement": "TLR2 glycosylation affects ligand binding and immune signaling.", "mechanism": "TLR2 recognizes viral proteins, mediates microglial activation and antigen presentation in demyelinating disease.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "BBB dysfunction", "glycan_involvement": "Tat interacts with glycoproteins at BBB; glycosylation may modulate effects.", "mechanism": "Tat alters tight junction protein expression, increases BBB permeability, and promotes neurotoxicity.", "protein": "HIV-1 Tat", "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "Progressive multifocal leukoencephalopathy", "glycan_involvement": "Galactosylceramide is a glycosphingolipid; glycan moiety mediates gp120 interaction.", "mechanism": "gp120 binding to galactosylceramide on oligodendrocytes reduces myelin synthesis and induces apoptosis.", "protein": "Galactosylceramide", "relationship_type": "causal", "source_pmcid": "PMC7173529" }, { "confidence": "medium", "disease": "HIV encephalitis", "glycan_involvement": "ICAM-1 glycosylation regulates cell adhesion and immune interactions.", "mechanism": "Upregulated in microglia during HIV infection, facilitates immune cell recruitment and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7173529" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation of gp120 and host receptors is essential for binding and viral entry.", "mechanism": "gp120 binds CD4 and chemokine receptor glycoproteins to mediate HIV entry into host cells.", "protein": "HIV gp120 (SU glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation of HA and host cell receptors determines virus attachment and host specificity.", "mechanism": "HA binds to sialic acid-containing glycan receptors on host cell glycoproteins/glycolipids to initiate infection.", "protein": "Influenza Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "CD4 glycosylation affects gp120 binding affinity.", "mechanism": "CD4 is the primary receptor for HIV entry; blocking CD4-gp120 interaction inhibits infection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173567" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates receptor function and HIV tropism.", "mechanism": "Serve as coreceptors for HIV entry after gp120-CD4 binding.", "protein": "Chemokine receptors (CCR5, CXCR4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "General viral infections", "glycan_involvement": "Glycosylation is necessary for fusion protein folding and activity.", "mechanism": "Fusion proteins mediate membrane fusion for viral entry, requiring glycosylation for proper function.", "protein": "Viral fusion proteins", "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "General viral infections", "glycan_involvement": "Glycosylation determines receptor binding and immune evasion.", "mechanism": "Envelope glycoproteins interact with host cell glycoproteins/glycolipids for attachment and entry.", "protein": "Viral envelope glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "General viral infections", "glycan_involvement": "Glycosylation provides viral binding sites.", "mechanism": "Serve as viral receptors; density and glycosylation state affect susceptibility.", "protein": "Cell surface glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "General viral infections", "glycan_involvement": "Polysaccharide composition modulates viral access.", "mechanism": "Glycocalyx can act as a barrier or facilitate viral attachment via glycan binding.", "protein": "Glycocalyx polysaccharide-associated proteins", "relationship_type": "protective/causal", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "General viral infections", "glycan_involvement": "Glycan residues on receptors are critical for viral attachment.", "mechanism": "Capsid proteins interact with glycosylated cell surface receptors for entry.", "protein": "Picornavirus capsid proteins", "relationship_type": "causal", "source_pmcid": "PMC7173567" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may affect processing and function.", "mechanism": "Proteolytic cleavage of polyproteins is required for maturation; inhibitors block infectious virus production.", "protein": "Retroviral polyproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7173567" }, { "confidence": "high", "disease": "Fibropapillomatosis", "glycan_involvement": "Glycoprotein H is a viral envelope glycoprotein; glycosylation is essential for antigenicity and immune recognition.", "mechanism": "Antibodies against glycoprotein H are detected in infected turtles; used in ELISA for diagnosis.", "protein": "Herpesvirus glycoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC7173601" }, { "confidence": "high", "disease": "Lung, eye, and trachea disease (LETD)", "glycan_involvement": "Glycosylation of glycoprotein H mediates immune response detection.", "mechanism": "Antibodies against glycoprotein H detected in LETD cases; ELISA used for serodiagnosis.", "protein": "Herpesvirus glycoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC7173601" }, { "confidence": "medium", "disease": "Herpesvirus-associated stomatitis/glossitis", "glycan_involvement": "Glycosylation of glycoprotein H is required for antigenicity.", "mechanism": "Serology (ELISA, neutralization) detects antibodies to glycoprotein H in tortoises with stomatitis/glossitis.", "protein": "Herpesvirus glycoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC7173601" }, { "confidence": "medium", "disease": "Herpesvirus hepatitis", "glycan_involvement": "Glycosylation mediates immune recognition.", "mechanism": "Antibodies to glycoprotein H detected in animals with hepatic necrosis due to herpesvirus.", "protein": "Herpesvirus glycoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC7173601" }, { "confidence": "high", "disease": "Testudinid herpesvirus infection", "glycan_involvement": "Glycosylation required for serological detection.", "mechanism": "ELISA and neutralization tests for glycoprotein H antibodies used to diagnose infection.", "protein": "Herpesvirus glycoprotein H", "relationship_type": "biomarker", "source_pmcid": "PMC7173601" }, { "confidence": "high", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Glycosylation affects receptor binding, immune evasion, and antigenicity.", "mechanism": "Mediates viral entry via receptor binding and membrane fusion; determines tissue tropism and host range.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Bluecomb disease (mud fever)", "glycan_involvement": "Glycosylation modulates host specificity and immune recognition.", "mechanism": "Facilitates entry into intestinal epithelium of turkeys.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Pheasant respiratory and kidney disease", "glycan_involvement": "Glycosylation influences tissue tropism and immune escape.", "mechanism": "Enables infection of respiratory and renal tissues in pheasants.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "medium", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "N-linked/O-linked glycans may affect assembly and immune recognition.", "mechanism": "Essential for virion assembly and formation of virus-like particles.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "medium", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Glycosylation status may influence assembly efficiency.", "mechanism": "Required for virion assembly and budding.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity.", "mechanism": "Targeted in RT-PCR and serological assays for diagnosis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Not glycosylated; not relevant.", "mechanism": "Used in diagnostic PCR assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Glycosylation influences immunogenicity and vaccine efficacy.", "mechanism": "Target of vaccine-induced immunity.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7176155" }, { "confidence": "medium", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Glycosylation may affect VLP formation and immunogenicity.", "mechanism": "M protein plus E protein used to generate virus-like particles for vaccine development.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7176155" }, { "confidence": "medium", "disease": "Infectious bronchitis of poultry", "glycan_involvement": "Altered glycosylation modulates tissue tropism and pathogenicity.", "mechanism": "Mutations and glycosylation changes in S protein linked to emergence of nephropathogenic strains.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7176155" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Heavily N-glycosylated; glycosylation critical for folding, immune evasion, and receptor binding.", "mechanism": "Mediates viral entry via ACE2, initiates infection and pathogenesis.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "high", "disease": "SARS-associated pneumonia", "glycan_involvement": "Glycosylation modulates immune recognition and cytokine induction.", "mechanism": "Spike triggers host immune and inflammatory responses leading to lung pathology.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "high", "disease": "Hyperinflammatory response", "glycan_involvement": "Glycosylation affects interaction with immune lectins (e.g., DC-SIGN).", "mechanism": "Induces IL8 receptor expression and cytokine storm.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "medium", "disease": "Cytopathic effect (CPE)", "glycan_involvement": "Glycosylation required for proper spike trafficking and function.", "mechanism": "Disrupts cytoskeletal gene expression, leading to cell death.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "medium", "disease": "Immune activation", "glycan_involvement": "Glycosylation influences antigenicity and immune detection.", "mechanism": "Upregulates MHC class I and B-cell transcription factors.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "medium", "disease": "Viral-induced cell cycle dysregulation", "glycan_involvement": "Glycosylation required for spike-mediated signaling.", "mechanism": "Alters expression of cyclins, histones, and cell cycle regulators.", "protein": "SARS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7176169" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Binds high-mannose N-glycans on spike protein.", "mechanism": "Facilitates SARS-CoV entry into dendritic cells via spike glycan recognition.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "facilitator", "source_pmcid": "PMC7176169" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Recognizes spike N-glycans.", "mechanism": "Mediates alternative cell entry for SARS-CoV via spike glycan binding.", "protein": "L-SIGN (CD209L)", "protein_enriched": { "function": "Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Is a rec", "gene_name": "CLEC4M", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9H2X3" }, "relationship_type": "facilitator", "source_pmcid": "PMC7176169" }, { "confidence": "medium", "disease": "Immune activation", "glycan_involvement": "Glycosylation modulates cell surface expression.", "mechanism": "Downregulated in spike-expressing cells, indicating altered immune cell signaling.", "protein": "CD53 glycoprotein", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling (PubMed:28487417). Participat", "gene_name": "CD53", "glycan_count": 4, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G05962QB", "G57776ZS", "G70232NH", "G79666IR" ], "uniprot_id": "P19397" }, "relationship_type": "biomarker", "source_pmcid": "PMC7176169" }, { "confidence": "medium", "disease": "Immune activation", "glycan_involvement": "N-glycosylation required for MHC class I stability and function.", "mechanism": "Upregulated by spike, enhancing antigen presentation.", "protein": "Major histocompatibility complex, class I, A", "relationship_type": "biomarker", "source_pmcid": "PMC7176169" }, { "confidence": "high", "disease": "Gonorrhea", "glycan_involvement": "IgA glycosylation is essential for mucosal stability and function.", "mechanism": "IgA in mucosal secretions prevents Neisseria gonorrhoeae from anchoring to host tissues.", "protein": "IgA", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Bacterial meningitis", "glycan_involvement": "Glycosylation of SIgA is critical for resistance to bacterial proteases.", "mechanism": "SIgA neutralizes pathogens like Neisseria meningitidis at mucosal surfaces.", "protein": "SIgA", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Strep throat", "glycan_involvement": "MBL recognizes mannose-rich glycans on bacteria.", "mechanism": "MBL binds bacterial surface glycans, activating lectin complement pathway to clear Streptococcus pyogenes.", "protein": "MBL (Mannose-binding lectin)", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Cholera", "glycan_involvement": "C3b binds to bacterial surface glycans (LPS/peptidoglycan).", "mechanism": "C3b opsonizes Vibrio cholerae, promoting phagocytosis and clearance.", "protein": "C3b", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Bacterial meningitis", "glycan_involvement": "Sialic acid-rich glycans degrade C3b and block complement.", "mechanism": "Capsule in Neisseria meningitidis and group B Streptococcus inhibits complement activation and phagocytosis.", "protein": "Sialic acid-containing capsule", "relationship_type": "causal", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Viral infections (general)", "glycan_involvement": "Glycosylation of host receptors is required for viral attachment.", "mechanism": "Viruses bind to host cell surface glycoprotein receptors to gain entry.", "protein": "Host cell glycoprotein receptors", "relationship_type": "causal", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Septic shock (from Gram-negative bacteria)", "glycan_involvement": "LPS glycan structure is essential for TLR4 activation.", "mechanism": "TLR4 recognizes LPS glycan on bacteria, triggering cytokine storm.", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC7184559" }, { "confidence": "medium", "disease": "Septic shock (from Gram-positive bacteria)", "glycan_involvement": "Glycosylation of bacterial ligands affects TLR2 signaling.", "mechanism": "TLR2 recognizes bacterial glycoproteins/lipoglycans, leading to cytokine release.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC7184559" }, { "confidence": "medium", "disease": "Food poisoning", "glycan_involvement": "Fc glycosylation modulates FcR binding affinity.", "mechanism": "FcR on phagocytes binds antibody-opsonized Staphylococcus aureus for clearance.", "protein": "Fc receptor (FcR)", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "medium", "disease": "Parasitic infections (general)", "glycan_involvement": "IgE glycosylation is required for receptor binding and effector function.", "mechanism": "IgE binds to parasite antigens, triggering degranulation of mast cells and eosinophils.", "protein": "IgE", "relationship_type": "protective", "source_pmcid": "PMC7184559" }, { "confidence": "high", "disease": "Hemolytic transfusion reaction", "glycan_involvement": "Blood group antigens are defined by glycan structures on glycoproteins.", "mechanism": "Mismatched glycoprotein antigens on RBCs trigger immune-mediated destruction of transfused cells.", "protein": "Dog erythrocyte surface glycoproteins (blood group antigens)", "relationship_type": "causal", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Antithrombin is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Antithrombin depletion contributes to uncontrolled coagulation in DIC; plasma therapy replenishes antithrombin.", "protein": "Antithrombin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "DIC", "glycan_involvement": "N-glycosylation critical for secretion and activity.", "mechanism": "Decreased glycoprotein coagulation factors worsen bleeding; plasma/cryoprecipitate therapy replenishes them.", "protein": "Coagulation factors (e.g., Factor VIII, IX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "Severe hypoproteinemia", "glycan_involvement": "Albumin is glycosylated, affecting half-life and function.", "mechanism": "Low albumin levels indicate or contribute to hypoproteinemia; plasma therapy partially replenishes albumin.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "Sepsis/Septic shock", "glycan_involvement": "Fc glycosylation modulates immune effector functions.", "mechanism": "Immunoglobulins in plasma support immune defense during sepsis.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "Thrombocytopathia", "glycan_involvement": "Glycosylation required for platelet adhesion and aggregation.", "mechanism": "Defective platelet glycoproteins impair clot formation, leading to bleeding.", "protein": "Platelet glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7186847" }, { "confidence": "medium", "disease": "Protein-losing enteropathy/nephropathy", "glycan_involvement": "Glycosylation affects renal clearance.", "mechanism": "Loss of antithrombin glycoprotein in urine or gut increases risk of thrombosis.", "protein": "Antithrombin", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7186847" }, { "confidence": "high", "disease": "Lung adenocarcinoma", "glycan_involvement": "N-glycosylation affects stability and localization.", "mechanism": "Napsin A is highly expressed in pneumocytes and adenocarcinoma cells, used for diagnosis.", "protein": "Napsin A", "protein_enriched": { "function": "May be involved in processing of pneumocyte surfactant precursors", "gene_name": "NAPSA", "glycan_count": 76, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G01485JJ", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G07246CJ", "G07755XJ", "G08290VR", "G08918WF", "G10819WX", "G11314AS", "G12341GU", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23505EP", "G23719VF", "G25079LO", "G27058EU", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G35029YA", "G36379GD", "G37412TK", "G37509XX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G43769HG", "G45395BF", "G45504EY", "G47644PP", "G49018RC", "G49906RN", "G49955PK", "G50282JC", "G54010QB", "G57317CE", "G57776ZU", "G58954YZ", "G60033FS", "G62765YT", "G63980BQ", "G65184UU", "G68490OW", "G69521XL", "G70619PT", "G72787SB", "G72790NZ", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80920RR", "G83460ZZ", "G83633GK", "G83646BJ", "G84225JN", "G84349RE", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G87123QX", "G87389XI", "G87661QW", "G90382BL", "G90659AW", "G92050GC", "G92275SC", "G95177YH", "G95865ZB" ], "uniprot_id": "O96009" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Invasive mucinous adenocarcinoma", "glycan_involvement": "O-glycosylation is essential for mucin gel formation.", "mechanism": "MUC2 is overexpressed in mucinous adenocarcinomas, indicating mucinous differentiation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Invasive mucinous adenocarcinoma", "glycan_involvement": "O-glycosylation critical for mucin function.", "mechanism": "MUC5AC is a marker for mucinous phenotype in lung tumors.", "protein": "MUC5AC", "protein_enriched": { "function": "May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing. Binds P.aeruginosa pili", "gene_name": "MUC7", "glycan_count": 22, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G49108TO", "G00031MO", "G17050CK", "G21153FA", "G21672LC", "G26341TZ", "G29931IJ", "G40142JY", "G41245OZ", "G43059PA", "G46748BU", "G49854OS", "G57321FI", "G63760GT", "G65562ZE", "G72336LC", "G74722FL", "G76163CP", "G79243QP", "G80700YJ", "G88779RV", "G94435QH" ], "uniprot_id": "Q8TAX7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "medium", "disease": "Invasive mucinous adenocarcinoma", "glycan_involvement": "O-glycosylation required for mucin structure.", "mechanism": "MUC6 expression supports mucinous differentiation in lung tumors.", "protein": "MUC6", "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Small cell lung carcinoma", "glycan_involvement": "N-glycosylation modulates cell adhesion.", "mechanism": "CD56 is highly expressed in neuroendocrine tumors including small cell carcinoma.", "protein": "CD56 (NCAM1)", "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Carcinoid tumor (lung)", "glycan_involvement": "N-glycosylation affects secretion and stability.", "mechanism": "Chromogranin A is a neuroendocrine marker for carcinoid tumors.", "protein": "Chromogranin A", "protein_enriched": { "function": "Strongly inhibits glucose induced insulin release from the pancreas", "gene_name": "CHGA", "glycan_count": 8, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00031MO", "G01614ZM", "G29931IJ", "G57321FI", "G65562ZE", "G74722FL", "G81006GJ", "G43417UB" ], "uniprot_id": "P10645" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Large cell neuroendocrine carcinoma", "glycan_involvement": "Glycosylation affects membrane localization.", "mechanism": "Synaptophysin is used to confirm neuroendocrine differentiation.", "protein": "Synaptophysin", "protein_enriched": { "function": "Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic p", "gene_name": "SYP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P08247" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "medium", "disease": "Lung adenocarcinoma", "glycan_involvement": "Glycosylation may affect filament assembly.", "mechanism": "CK7 is expressed in adenocarcinoma cells, aiding in diagnosis.", "protein": "CK7", "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "medium", "disease": "Pulmonary hamartoma", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "AE1/3 stains epithelial elements in hamartoma.", "protein": "AE1/3", "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "low", "disease": "Pulmonary amyloidosis", "glycan_involvement": "O-glycosylation influences amyloid formation.", "mechanism": "Mucinous glycoproteins can be components of amyloid deposits.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC7189424" }, { "confidence": "high", "disease": "Thrombotic disorders", "glycan_involvement": "Glycosylation of \u03b1-DG increases ligand binding to ECM proteins (laminin, fibronectin), enhancing platelet-platelet and platelet-ECM interactions.", "mechanism": "\u03b1-DG mediates platelet adhesion and aggregation via ECM binding; blocking \u03b1-DG inhibits thrombus formation.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7191674" }, { "confidence": "high", "disease": "Thrombotic disorders", "glycan_involvement": "Increased glycosylation after thrombin activation enhances \u03b1-DG's affinity for ECM ligands.", "mechanism": "Post-translational modifications (glycosylation, proteolytic cleavage) of \u03b1-DG upon platelet activation increase its adhesive function, promoting thrombus formation.", "protein": "\u03b1-dystroglycan (\u03b1-DG)", "relationship_type": "causal", "source_pmcid": "PMC7191674" }, { "confidence": "medium", "disease": "Thrombotic disorders", "glycan_involvement": "Glycosylation of \u03b1-DG is required for fibronectin binding.", "mechanism": "Fibronectin forms a complex with \u03b1-DG and \u03b1IIb\u03b23 integrin, facilitating platelet aggregation.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC7191674" }, { "confidence": "medium", "disease": "Thrombotic disorders", "glycan_involvement": "Complex formation depends on glycosylated \u03b1-DG.", "mechanism": "\u03b1IIb\u03b23 integrin interacts with glycosylated \u03b1-DG and fibronectin to mediate platelet aggregation.", "protein": "\u03b1IIb\u03b23 integrin", "relationship_type": "causal", "source_pmcid": "PMC7191674" }, { "confidence": "medium", "disease": "Cancer metastasis", "glycan_involvement": "GLUT1 is a glycoprotein; its abundance and function may be regulated by glycosylation, though not directly studied here.", "mechanism": "SGK-1 upregulates GLUT1, promoting glucose uptake and ATP production in ECM-detached cancer cells, supporting survival and metastasis.", "protein": "GLUT1", "protein_enriched": { "function": "Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, P", "gene_name": "SLC2A1", "glycan_count": 9, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G11115RO", "G11314AS", "G44753VC", "G68490OW", "G80920RR", "G98611JV", "G49108TO", "G60230HH", "G70101JE" ], "uniprot_id": "P11166" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7191674" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin by glucose.", "mechanism": "HbA1c reflects average blood glucose over prior 2-3 months.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Glycation status reflects metabolic dysregulation.", "mechanism": "Higher HbA1c correlates with elevated ALT, a marker for NAFLD risk.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect stability and serum levels.", "mechanism": "Elevated ALT is associated with hepatic fat accumulation in NAFLD.", "protein": "Alanine transaminase (ALT)", "protein_enriched": { "function": "", "gene_name": "AMY2A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04746" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "low", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect serum half-life.", "mechanism": "AST is measured as a liver function marker, but no significant correlation with HbA1c found.", "protein": "Aspartate transaminase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "high", "disease": "Hashimoto\u2019s Thyroiditis (Hypothyroidism)", "glycan_involvement": "Antibody glycosylation modulates immune effector functions.", "mechanism": "Anti-TPO antibodies mediate autoimmune destruction of thyroid tissue.", "protein": "Anti-TPO antibody", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7207446" }, { "confidence": "high", "disease": "Celiac Disease", "glycan_involvement": "IgA glycosylation affects antibody stability and immune response.", "mechanism": "Presence of tTG-IgA antibodies indicates autoimmune response against tissue transglutaminase.", "protein": "Celiac antibodies (tTG-IgA)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7207446" }, { "confidence": "medium", "disease": "Microvascular Complications", "glycan_involvement": "Glycation of hemoglobin reflects chronic hyperglycemia.", "mechanism": "HbA1c is used to assess risk for neuropathy, retinopathy, nephropathy, but no significant association found in this study.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "low", "disease": "Vitamin B12 Deficiency", "glycan_involvement": "Indirect; altered erythrocyte turnover affects HbA1c measurement.", "mechanism": "Vitamin B12 deficiency is prevalent in type 1 DM; HbA1c may be affected by anemia.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "low", "disease": "Vitiligo", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Vitiligo is an autoimmune comorbidity in type 1 DM; HbA1c reflects glycemic control.", "protein": "Hemoglobin A1c (HbA1c)", "protein_enriched": { "function": "Involved in oxygen transport from the lung to the various peripheral tissues", "gene_name": "HBA1", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P69905" }, "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Antibody glycosylation modulates immune response.", "mechanism": "Anti-TPO antibodies indicate increased risk for thyroid autoimmunity in type 1 DM.", "protein": "Anti-TPO antibody", "relationship_type": "biomarker", "source_pmcid": "PMC7207446" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TSHR is a glycoprotein; glycosylation affects receptor conformation and autoantibody recognition", "mechanism": "Autoantibodies bind to TSHR, stimulating thyroid hormone production", "protein": "Thyrotropin receptor (TSHR)", "relationship_type": "causal", "source_pmcid": "PMC7207606" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "TRAb is an IgG glycoprotein; Fc glycosylation modulates effector function", "mechanism": "TRAb detected in serum is diagnostic for Graves' disease", "protein": "Thyrotropin receptor autoantibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC7207606" }, { "confidence": "high", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Insulin stimulates glycogen synthesis; not a glycoprotein but regulates glycan (glycogen) metabolism.", "mechanism": "High insulin levels promote excessive hepatic glycogen deposition, leading to hepatomegaly and liver dysfunction.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC7208124" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Insulin therapy affects hepatic glycogen storage.", "mechanism": "Exogenous insulin is required for glucose regulation in T1DM.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7208124" }, { "confidence": "high", "disease": "Diabetic Ketoacidosis (DKA)", "glycan_involvement": "Restores normal glucose and glycogen metabolism.", "mechanism": "Insulin deficiency leads to DKA; insulin administration reverses it.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7208124" }, { "confidence": "high", "disease": "Hypoglycemia", "glycan_involvement": "Insulin is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Excess insulin (endogenous or exogenous) lowers blood glucose, causing hypoglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC7208142" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "Proinsulin is glycosylated, which affects its processing to insulin.", "mechanism": "Elevated proinsulin indicates inappropriate endogenous insulin secretion during hypoglycemia.", "protein": "Proinsulin", "relationship_type": "biomarker", "source_pmcid": "PMC7208142" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "C-peptide is a glycoprotein; glycosylation may affect its stability.", "mechanism": "Elevated C-peptide with hypoglycemia suggests endogenous insulin secretion.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7208142" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "TSH is heavily glycosylated, which affects its bioactivity and half-life.", "mechanism": "TSH levels help rule out hypothyroidism as a cause of hypoglycemia.", "protein": "TSH", "relationship_type": "biomarker", "source_pmcid": "PMC7208142" }, { "confidence": "medium", "disease": "Hypoglycemia", "glycan_involvement": "ACTH is glycosylated, which may affect its secretion and stability.", "mechanism": "ACTH levels help assess adrenal function in hypoglycemia.", "protein": "ACTH", "relationship_type": "biomarker", "source_pmcid": "PMC7208142" }, { "confidence": "high", "disease": "Breast cancer (HR-positive, HER-2 negative)", "glycan_involvement": "Not specified", "mechanism": "PI3K pathway is commonly mutated in breast cancer; inhibition used for therapy.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7208398" }, { "confidence": "high", "disease": "Hyperglycemia", "glycan_involvement": "Not specified", "mechanism": "PI3K inhibitor (alpelisib) therapy induces hyperglycemia, possibly via effects on glucose metabolism.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7208398" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus (T2DM)", "glycan_involvement": "Not specified", "mechanism": "PI3K inhibition can precipitate new onset T2DM in susceptible individuals.", "protein": "PI3K", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7208398" }, { "confidence": "high", "disease": "Breast cancer (HR-positive, HER-2 negative)", "glycan_involvement": "HER-2 is a glycoprotein; glycosylation affects receptor function and stability.", "mechanism": "HER-2 status is used to classify and guide therapy in breast cancer.", "protein": "HER-2 (ERBB2)", "relationship_type": "biomarker", "source_pmcid": "PMC7208398" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSI is an immunoglobulin with N-glycosylation important for stability and receptor interaction.", "mechanism": "TSI binds to TSHR, stimulating thyroid hormone production and causing hyperthyroidism.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC7208535" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSHR is a glycoprotein; N-glycosylation affects receptor conformation and antibody binding.", "mechanism": "Autoantibodies (TSI) activate TSHR, leading to excessive thyroid hormone release.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC7208535" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "SHBG is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "SHBG levels are higher in men with HIV compared to uninfected men.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "high", "disease": "Accelerated aging", "glycan_involvement": "Glycosylation may modulate SHBG's age-related changes.", "mechanism": "SHBG increases with age, and the rate of increase is greater in men with HIV, supporting accelerated aging.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "medium", "disease": "Immunodeficiency (low CD4+ T cell count)", "glycan_involvement": "Glycosylation may influence SHBG's interaction with immune status.", "mechanism": "Higher SHBG levels are associated with lower CD4+ T cell counts in men with HIV.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Glycosylation may affect SHBG's metabolic functions.", "mechanism": "SHBG may directly affect glucose metabolism; diabetes was considered as a comorbidity in the analysis.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "low", "disease": "Kidney disease", "glycan_involvement": "Glycosylation may affect SHBG clearance by the kidney.", "mechanism": "Kidney disease was included as a comorbidity; SHBG levels may be influenced by renal function.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "Glycosylation occurs in the liver and affects SHBG secretion.", "mechanism": "Liver disease was included as a comorbidity; SHBG is synthesized in the liver.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Glycosylation changes may occur in cancer affecting SHBG.", "mechanism": "Cancer was included as a comorbidity; SHBG may be altered in malignancy.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "low", "disease": "Depression", "glycan_involvement": "No direct evidence.", "mechanism": "Depression was included as a comorbidity; possible indirect association.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "No direct evidence.", "mechanism": "Hypertension was included as a comorbidity; possible indirect association.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "medium", "disease": "Hepatitis C virus infection", "glycan_involvement": "Glycosylation may be altered in hepatitis C affecting SHBG.", "mechanism": "Hepatitis C infection was adjusted for; may affect SHBG via liver function.", "protein": "Sex hormone-binding globulin (SHBG)", "relationship_type": "biomarker", "source_pmcid": "PMC7208560" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSI is an immunoglobulin with N-glycosylation affecting stability and immune recognition.", "mechanism": "TSI binds TSHR, stimulating thyroid hormone production and driving autoimmunity.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "Graves' Ophthalmopathy", "glycan_involvement": "Glycosylation of TSI modulates its immune activity and receptor binding.", "mechanism": "High TSI levels correlate with onset and exacerbation of ophthalmopathy via orbital fibroblast activation.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "TSHR is N-glycosylated, which affects receptor conformation and autoantibody binding.", "mechanism": "TSHR is targeted by TSI, leading to hyperthyroidism.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7208773" }, { "confidence": "medium", "disease": "Graves' Ophthalmopathy", "glycan_involvement": "N-glycosylation of TSHR influences its immunogenicity and cell surface expression.", "mechanism": "TSHR expression in orbital tissues mediates immune cell infiltration and tissue remodeling.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "causal", "source_pmcid": "PMC7208773" }, { "confidence": "medium", "disease": "Latent Tuberculosis", "glycan_involvement": "Interferon-gamma is glycosylated, affecting secretion and receptor interaction.", "mechanism": "Elevated interferon-gamma release assay indicates latent TB infection.", "protein": "Interferon-gamma", "relationship_type": "biomarker", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "Graves' Disease", "glycan_involvement": "Glycosylation patterns of TSI may influence pathogenicity.", "mechanism": "TSI drives autoimmune thyroid destruction and hyperthyroidism.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "Graves' Ophthalmopathy", "glycan_involvement": "Altered glycosylation may enhance TSI pathogenicity.", "mechanism": "TSI levels rise during disease exacerbation, reflecting immune activation.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC7208773" }, { "confidence": "medium", "disease": "Graves' Ophthalmopathy", "glycan_involvement": "Glycosylation status may affect therapeutic antibody binding.", "mechanism": "TSHR is a target for immunomodulatory therapies in ophthalmopathy.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "Graves' Ophthalmopathy", "glycan_involvement": "N-glycosylation of TSI influences immune effector functions.", "mechanism": "TSI triggers orbital fibroblast activation and inflammation.", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC7208773" }, { "confidence": "medium", "disease": "Graves' Disease", "glycan_involvement": "N-glycosylation modulates antigenicity.", "mechanism": "TSHR autoantibody binding is diagnostic for Graves' disease.", "protein": "Thyroid Stimulating Hormone Receptor (TSHR)", "protein_enriched": { "function": "Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin ", "gene_name": "TSHR", "glycan_count": 3, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G22573RC", "G70619PT", "G96091TT" ], "uniprot_id": "P16473" }, "relationship_type": "biomarker", "source_pmcid": "PMC7208773" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding and requires furin cleavage for activation.", "protein": "SARS-CoV-2 Spike glycoprotein (S)", "relationship_type": "causal", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Processes glycoproteins by cleaving at specific motifs; activity essential for glycoprotein maturation.", "mechanism": "Cleaves S glycoprotein at S1/S2 and S2' sites, enabling viral entry and cell-cell fusion.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Env is heavily glycosylated; furin cleavage required for functional glycoprotein formation.", "mechanism": "Cleaves HIV Env gp160 into gp120/gp41, essential for viral infectivity.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA is glycosylated; furin cleavage site is critical for pathogenicity.", "mechanism": "Cleaves hemagglutinin (HA) for viral activation and infectivity.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "medium", "disease": "Measles", "glycan_involvement": "F glycoprotein is glycosylated; cleavage required for activation.", "mechanism": "Cleaves measles virus F glycoprotein, required for viral fusion and entry.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "GM-CSF is a glycoprotein; glycosylation affects stability and receptor interaction.", "mechanism": "Enhances alveolar macrophage function, epithelial repair, and antiviral immunity.", "protein": "GM-CSF", "relationship_type": "protective", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates GM-CSF function.", "mechanism": "Promotes immune cell activation and epithelial repair, reducing lung injury.", "protein": "GM-CSF", "relationship_type": "protective", "source_pmcid": "PMC7249572" }, { "confidence": "medium", "disease": "Metapneumovirus infection", "glycan_involvement": "F protein is glycosylated; furin cleavage essential for function.", "mechanism": "Requires furin cleavage for activation and viral entry.", "protein": "Metapneumovirus F protein", "relationship_type": "causal", "source_pmcid": "PMC7249572" }, { "confidence": "medium", "disease": "Cancer (Ewing's sarcoma, ovarian cancer)", "glycan_involvement": "TGF\u03b2s are glycoproteins; glycosylation affects secretion and activity.", "mechanism": "Downstream of furin; furin knockdown reduces TGF\u03b21/2, impacting tumor progression.", "protein": "TGF\u03b21/2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "medium", "disease": "Pseudomonas aeruginosa corneal infection", "glycan_involvement": "Furin processes host glycoproteins involved in infection response.", "mechanism": "Furin inhibitors reduce corneal damage by blocking activation of bacterial/host glycoproteins.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7249572" }, { "confidence": "high", "disease": "Measles-induced secondary infections", "glycan_involvement": "Glycosylation of H/F complex mediates host cell binding and immunosuppressive signaling.", "mechanism": "Suppresses T cell proliferation via interference with cell cycle progression and PI3K signaling.", "protein": "Measles virus H/F glycoprotein complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavy N-glycosylation shields gp120 from immune recognition and modulates host interactions.", "mechanism": "Binds CD4 and CCR5/CXCR4, mediates T cell depletion and immune exhaustion.", "protein": "HIV gp120", "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation affects fusion efficiency and immune evasion.", "mechanism": "Facilitates viral fusion and entry into CD4+ cells.", "protein": "HIV gp41", "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "Influenza-induced secondary bacterial pneumonia", "glycan_involvement": "Enzymatic activity targets host glycans, facilitating bacterial superinfection.", "mechanism": "Cleaves host sialic acids, exposing receptors for S. pneumoniae adherence.", "protein": "Influenza virus neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "medium", "disease": "Measles-induced secondary infections", "glycan_involvement": "Glycosylation of CD46 required for measles virus interaction.", "mechanism": "Measles virus binding to CD46 modulates Th2 polarization and suppresses IL-12 production.", "protein": "CD46", "protein_enriched": { "function": "Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in th", "gene_name": "CD46", "glycan_count": 60, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G22768VO", "G61846BY", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G25451PN", "G27058EU", "G34989PA", "G40834TG", "G41071NU", "G43223CG", "G45395BF", "G48414YA", "G59324HL", "G60033FS", "G60177UT", "G62765YT", "G70232NH", "G70441OD", "G80075MS", "G80920RR", "G83229XP", "G83646BJ", "G84452RH", "G85282JO", "G86182NS", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G94470IW", "G98611JV", "G57321FI", "G03644CB", "G04854VP", "G07810QS", "G08290VR", "G12341GU", "G13131HA", "G15169WU", "G20706XG", "G23719VF", "G28622IK", "G31852PQ", "G41247ZX", "G43669FQ", "G50856PC", "G57776ZS", "G61256FT", "G69521XL", "G76417NN", "G78649WQ", "G82443XX", "G89827JR", "G90382BL", "G92275SC", "G92551JA", "G94106MV", "G49108TO" ], "uniprot_id": "P15529" }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "medium", "disease": "Measles-induced secondary infections", "glycan_involvement": "Glycosylation modulates receptor function and viral binding.", "mechanism": "Measles virus binding downregulates CD150, impairing T cell activation.", "protein": "CD150 (SLAMF1)", "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "Leishmaniasis-induced secondary infections", "glycan_involvement": "IL-10 is a glycoprotein; glycosylation affects secretion and stability.", "mechanism": "Elevated IL-10 suppresses Th1 immunity, increasing susceptibility to secondary infections.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation required for proper surface expression and immune modulation.", "mechanism": "HIV Nef/Tat downregulate classical MHC I but spare HLA-E, inhibiting NK cell activation.", "protein": "HLA-E", "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "medium", "disease": "Bordetella pertussis-induced pneumonia", "glycan_involvement": "Glycosylation mediates host cell binding and immune evasion.", "mechanism": "Adhesion to airway epithelium, delays neutrophil recruitment, increases risk of secondary pneumonia.", "protein": "Filamentous hemagglutinin (B. pertussis)", "protein_enriched": { "function": "S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of", "gene_name": "ptxA", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04977" }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "Malaria-induced secondary infections", "glycan_involvement": "Glycosylation affects IL-10 function and immune regulation.", "mechanism": "High IL-10 impairs dendritic cell maturation and vaccine efficacy, increases risk of co-infection.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "causal", "source_pmcid": "PMC7258708" }, { "confidence": "high", "disease": "Congenital disorder of glycosylation type 1", "glycan_involvement": "Direct; ERGIC-53 binds high-mannose N-glycans on cargo", "mechanism": "Defective ERGIC-53 impairs transport of glycoproteins from ER to Golgi", "protein": "p58/ERGIC-53", "protein_enriched": { "function": "Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or bo", "gene_name": "LMAN1", "glycan_count": 5, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI", "G49108TO", "G29068FM", "G43417UB", "G53434XO" ], "uniprot_id": "P49257" }, "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Human granulocytic anaplasmosis", "glycan_involvement": "Surface-exposed glycosylation mediates immune recognition", "mechanism": "Major outer membrane glycoprotein, target of immune response", "protein": "p44 (P44s of Anaplasma phagocytophilum)", "relationship_type": "biomarker", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Lyme disease", "glycan_involvement": "Glycosylation may affect antigenicity", "mechanism": "Elicits early IgM response in infection", "protein": "p37 (Borrelia burgdorferi P37)", "relationship_type": "biomarker", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Borna disease", "glycan_involvement": "Glycosylation required for proper folding and function", "mechanism": "Mediates viral entry via receptor-mediated endocytosis", "protein": "p56 (Borna disease virus surface glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Type 1 diabetes", "glycan_involvement": "Glycosylation may modulate antigenicity", "mechanism": "Autoantigen targeted in autoimmune destruction of islet cells", "protein": "p69 (Pancreatic islet cell autoantigen 1)", "relationship_type": "biomarker", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Surface glycosylation involved in host-pathogen interaction", "mechanism": "Essential for parasite infection of mosquitoes", "protein": "p25 (Plasmodium surface protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Viral infections (general)", "glycan_involvement": "Glycosylation critical for viral entry", "mechanism": "Major envelope glycoprotein in polyhedrosis viruses, required for infectivity", "protein": "p64", "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Antigen presentation defects", "glycan_involvement": "N-glycosylation required for trafficking and function", "mechanism": "Regulates MHC II stability and antigen loading", "protein": "p41 (MHC II-associated invariant chain)", "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Cargo trafficking disorders", "glycan_involvement": "Bind glycan motifs on cargo for sorting", "mechanism": "Defects impair ER-Golgi transport of glycoproteins", "protein": "p23/p24 (cargo receptors)", "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "medium", "disease": "Viral entry defects", "glycan_involvement": "Glycosylation essential for receptor binding", "mechanism": "Altered glycosylation impairs viral entry", "protein": "p56 (Borna disease virus surface glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC7271153" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Glycosylation affects AFP stability and detection.", "mechanism": "Elevated AFP in serum and tissue is a marker for HCC.", "protein": "Alpha fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Yolk sac tumor", "glycan_involvement": "Glycosylation is essential for immunodetection.", "mechanism": "AFP is produced by yolk sac tumors; used for diagnosis.", "protein": "Alpha fetoprotein (AFP)", "relationship_type": "biomarker", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Alpha-1-antitrypsin deficiency", "glycan_involvement": "Abnormal glycosylation can affect secretion and aggregation.", "mechanism": "Deficient or misfolded AAT accumulates in hepatocytes, causing liver disease.", "protein": "Alpha 1-antitrypsin (AAT)", "relationship_type": "causal", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Breast carcinoma", "glycan_involvement": "Glycosylation modulates receptor function and antibody binding.", "mechanism": "HER2 overexpression/amplification drives tumor growth; target for trastuzumab.", "protein": "HER2/neu (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Dialysis-associated amyloidosis", "glycan_involvement": "Glycosylation status affects amyloidogenicity.", "mechanism": "Beta-2-microglobulin accumulates and forms amyloid in long-term dialysis patients.", "protein": "Beta-2-microglobulin", "relationship_type": "causal", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "AA amyloidosis (secondary)", "glycan_involvement": "Glycosylation may influence aggregation and deposition.", "mechanism": "Chronic inflammation increases SAA, leading to amyloid deposition.", "protein": "Serum amyloid A protein (SAA)", "relationship_type": "causal", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Medullary thyroid carcinoma", "glycan_involvement": "Glycosylation required for hormone stability.", "mechanism": "Tumor cells produce calcitonin, detected in tissue and serum.", "protein": "Calcitonin", "protein_enriched": { "function": "Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones. Calcitonin function i", "gene_name": "CALCA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P01258" }, "relationship_type": "biomarker", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Familial amyloid polyneuropathy", "glycan_involvement": "Glycosylation may modulate amyloid formation.", "mechanism": "Mutant transthyretin forms amyloid fibrils in nerves and heart.", "protein": "Transthyretin", "relationship_type": "causal", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Primary amyloidosis (AL)", "glycan_involvement": "Glycosylation can affect aggregation propensity.", "mechanism": "Monoclonal light chains misfold and deposit as amyloid.", "protein": "Immunoglobulin light chains (AL)", "relationship_type": "causal", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Colorectal carcinoma", "glycan_involvement": "Heavily glycosylated; glycan structure affects detection.", "mechanism": "CEA is overexpressed in colorectal cancer; used for diagnosis and monitoring.", "protein": "Carcinoembryonic antigen (CEA)", "relationship_type": "biomarker", "source_pmcid": "PMC7271186" }, { "confidence": "high", "disease": "Glomerulonephritis", "glycan_involvement": "Altered glycosylation affects matrix composition and cell interactions.", "mechanism": "Mesangial matrix expansion and glycoprotein accumulation contribute to glomerular inflammation and dysfunction.", "protein": "Mesangial glycoprotein matrix", "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "high", "disease": "Glomerulonephritis", "glycan_involvement": "Loss of anionic glycoproteins disrupts charge-selective filtration.", "mechanism": "Immune complex deposition and GBM glycoprotein alteration lead to barrier dysfunction and proteinuria.", "protein": "Glomerular basement membrane (GBM) glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "high", "disease": "Protein-losing nephropathy", "glycan_involvement": "Glycosylation of nephrin is essential for slit diaphragm integrity.", "mechanism": "Disruption of nephrin in slit diaphragms impairs filtration barrier, causing proteinuria.", "protein": "Nephrin", "protein_enriched": { "function": "Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoske", "gene_name": "NPHS1", "glycan_count": 0, "glycosylation_sites_count": 10, "glytoucan_ids": [], "uniprot_id": "O60500" }, "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "Glycosylation modulates laminin interactions in the basement membrane.", "mechanism": "Altered laminin in GBM affects structural support and filtration.", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "high", "disease": "Protein-losing nephropathy", "glycan_involvement": "Sulfated glycosaminoglycan chains are critical for charge barrier.", "mechanism": "Loss of polyanionic proteoglycans reduces charge selectivity, leading to proteinuria.", "protein": "Polyanionic proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Renal fibrosis", "glycan_involvement": "Glycosylation regulates fibronectin deposition and cell adhesion.", "mechanism": "Fibronectin accumulation in ECM promotes fibrotic scarring.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "Glycosylation is important for entactin's structural role.", "mechanism": "Disruption of entactin affects basement membrane stability and filtration.", "protein": "Entactin (nidogen)", "protein_enriched": { "function": "The restriction (R) subunit of a type I restriction enzyme that recognizes 5'-GAAN(6)RTCG-3' (for EcoR124I) and 5'-GAAN(7)RTCG-3' (for EcoR124II) and cleaves a random distance away (PubMed:2784505). S", "gene_name": "hsdR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10486" }, "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation status influences amyloidogenicity.", "mechanism": "SAA deposition as amyloid in glomeruli leads to proteinuria and renal dysfunction.", "protein": "Serum amyloid-A (SAA)", "relationship_type": "causal", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Glycosylation affects plasma half-life and renal filtration.", "mechanism": "Loss of antithrombin III in urine due to glomerular barrier dysfunction increases thrombotic risk.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC7271189" }, { "confidence": "medium", "disease": "Chronic renal failure", "glycan_involvement": "Glycosaminoglycan chains mediate ECM expansion.", "mechanism": "Increased ECM acidic proteoglycans with age and ischemia contribute to interstitial fibrosis.", "protein": "Acidic proteoglycans", "relationship_type": "biomarker", "source_pmcid": "PMC7271189" }, { "confidence": "high", "disease": "Osteoarthritis", "glycan_involvement": "Direct use of glycosaminoglycan in ECM", "mechanism": "Injected as viscosupplement to improve joint lubrication and function", "protein": "Hyaluronic acid", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "medium", "disease": "Osteoarthritis", "glycan_involvement": "Precursor for glycosylation in proteoglycans", "mechanism": "Oral supplement thought to support cartilage glycoprotein synthesis", "protein": "Glucosamine", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "high", "disease": "Thromboembolism", "glycan_involvement": "Enzyme is a glycoprotein; glycosylation affects stability", "mechanism": "Inhibited by low-dose aspirin to reduce platelet aggregation", "protein": "Thromboxane A2 synthase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "high", "disease": "Thromboembolism", "glycan_involvement": "N-glycosylation required for secretion and function", "mechanism": "Aspirin affects synthesis/activity, reducing clotting", "protein": "Vitamin K-dependent coagulation factors", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Antibody glycosylation modulates immune activity", "mechanism": "Presence increases risk; aspirin used for prevention", "protein": "Anti-cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC7271212" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Antibody glycosylation modulates immune activity", "mechanism": "Associated with increased risk; aspirin prophylaxis", "protein": "Anti-phospholipid antibody", "relationship_type": "biomarker", "source_pmcid": "PMC7271212" }, { "confidence": "high", "disease": "Pre-eclampsia", "glycan_involvement": "Glycosylation affects enzyme activity", "mechanism": "Inhibited by aspirin/NSAIDs to reduce prostaglandin synthesis", "protein": "Prostaglandin-endoperoxide synthase (COX)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "high", "disease": "Ductus arteriosus closure", "glycan_involvement": "Glycoproteins in tissue ECM mediate closure", "mechanism": "NSAIDs/aspirin induce premature closure by inhibiting prostaglandin synthesis", "protein": "Ductus arteriosus Botalli (tissue)", "relationship_type": "causal", "source_pmcid": "PMC7271212" }, { "confidence": "medium", "disease": "Neonatal respiratory depression", "glycan_involvement": "Receptor glycosylation modulates ligand binding", "mechanism": "Opioid drugs cross placenta, activate fetal receptors", "protein": "Opioid receptors (\u03bc, \u03ba, \u03b4)", "relationship_type": "causal", "source_pmcid": "PMC7271212" }, { "confidence": "medium", "disease": "Chronic pain", "glycan_involvement": "Channel is glycosylated, affecting trafficking", "mechanism": "Ziconotide blocks channel to reduce pain", "protein": "NCCB (N-type calcium channel)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7271212" }, { "confidence": "high", "disease": "Anemia (especially in chronic kidney disease)", "glycan_involvement": "Glycosylation is essential for EPO stability and activity.", "mechanism": "EPO stimulates erythropoiesis to treat anemia.", "protein": "Erythropoietin (EPO)", "protein_enriched": { "function": "Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leadin", "gene_name": "EPO", "glycan_count": 208, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00551JZ", "G00553AN", "G01450UB", "G02311IE", "G02561FC", "G04959WS", "G09176OA", "G10148VG", "G10228OD", "G11528MV", "G11629QQ", "G12436UO", "G13165FV", "G13282WA", "G14199EY", "G15169WU", "G16208YZ", "G16529MG", "G16873YG", "G17155VX", "G17689DH", "G18639PA", "G18938DW", "G19603RR", "G20218ZS", "G22310AV", "G22721QX", "G23165GD", "G25392ZR", "G26777RD", "G27844UM", "G28103WK", "G29857RC", "G30460NZ", "G31596VW", "G31665QC", "G33284WZ", "G34617SM", "G36191CD", "G39595FH", "G39643OJ", "G39952PY", "G40027VO", "G40194MN", "G43761WH", "G45116BB", "G45359RY", "G45495MK", "G45883VE", "G47279LF", "G47518TP", "G48109OV", "G48488CO", "G49446SO", "G50489VC", "G50888WV", "G51057KO", "G53752TA", "G56516KW", "G56811US", "G57248BB", "G57581QG", "G57888GL", "G58598BO", "G62619LG", "G62765SF", "G63889NK", "G64394MX", "G67506FN", "G67610NV", "G68209WQ", "G68892PJ", "G69834CE", "G71549MK", "G72797UR", "G72886NH", "G74859XI", "G75520NV", "G78059CC", "G78166NF", "G79809MM", "G80537QW", "G81107PN", "G81263BG", "G82410AF", "G83108TD", "G83295QG", "G84331QL", "G84390MS", "G84452RH", "G86357DX", "G86696LV", "G86753CK", "G88696CU", "G88976TU", "G90093AU", "G90784AP", "G90789YQ", "G91152KU", "G91413ZX", "G91905FJ", "G92574YO", "G92709EO", "G94531EZ", "G94974XB", "G96503EZ", "G96719MC", "G98259QP", "G00031MO", "G01614ZM", "G19399OS", "G27945LI", "G29931IJ", "G46831QF", "G47190LU", "G47318KU", "G47967RK", "G48809BS", "G49644CL", "G56682BC", "G57321FI", "G60554YG", "G71838YU", "G74722FL", "G81006GJ", "G00249IY", "G03382KH", "G06330RB", "G08146BT", "G10773YW", "G14796IU", "G14994KB", "G23863VK", "G23869AA", "G25379SA", "G27290LL", "G29501UT", "G29880MM", "G31838XA", "G35364KM", "G44215PV", "G46687AB", "G48414YA", "G49874UX", "G50707YR", "G52122ZD", "G53492UE", "G54639VI", "G60984DZ", "G61962FK", "G62461SM", "G68796US", "G70375MX", "G70822IO", "G79568CQ", "G81295CK", "G83676GD", "G89098OM", "G90448RI", "G91636VS", "G93180LE", "G94309NZ", "G94854LT", "G97428EW", "G05813WO", "G12793SR", "G31153XO", "G42459UQ", "G52527GH", "G52782YT", "G55383ZG", "G60723SV", "G66163OV", "G72667IM", "G83213GG", "G93656SY", "G07410AW", "G09576QH", "G13441ZL", "G14389GM", "G14950CY", "G16679DU", "G19972YZ", "G20425TQ", "G23305TF", "G26775OX", "G28948UC", "G29097SS", "G31380TD", "G31544HA", "G31991IV", "G40428GO", "G45209NR", "G47012YE", "G50045TK", "G51562OR", "G53322JT", "G57789QC", "G58039UH", "G59742GY", "G65562ZE", "G70894RY", "G75154UG", "G77149EE", "G77582RK", "G84756CG", "G88027AL", "G98568VG" ], "uniprot_id": "P01588" }, "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "mABs target tumor antigens for immune-mediated destruction.", "protein": "Monoclonal antibodies (mABs)", "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "high", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation affects antibody function and half-life.", "mechanism": "mABs modulate immune responses.", "protein": "Monoclonal antibodies (mABs)", "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "high", "disease": "Viral infections", "glycan_involvement": "Glycosylation required for stability and activity.", "mechanism": "Interferon alpha-2a has antiviral and immunomodulatory effects.", "protein": "Interferon alpha-2a", "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation critical for function and half-life.", "mechanism": "Replacement of deficient clotting factor.", "protein": "Recombinant blood-clotting factor", "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "medium", "disease": "Immunodeficiency diseases", "glycan_involvement": "Fc glycosylation impacts immune effector functions.", "mechanism": "Passive immunization or immune modulation.", "protein": "Monoclonal antibodies (mABs)", "relationship_type": "therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates receptor binding and signaling.", "mechanism": "Dysregulation of growth factor signaling promotes tumorigenesis.", "protein": "Growth factors (EGF, PDGF, TGF-\u03b2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7325846" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation affects cell-matrix interactions.", "mechanism": "Altered cell adhesion and migration in tumor progression.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7325846" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Glycosylation required for stability and receptor interaction.", "mechanism": "Iron transport for erythropoiesis.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. 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"G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker/therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "low", "disease": "Aging-associated decline", "glycan_involvement": "Glycosylation mediates ECM interactions.", "mechanism": "Supports cell attachment and tissue integrity.", "protein": "Chondronectin", "relationship_type": "protective/therapeutic", "source_pmcid": "PMC7325846" }, { "confidence": "high", "disease": "Infectious mononucleosis", "glycan_involvement": "N-glycosylation critical for receptor binding and immune evasion.", "mechanism": "Mediates EBV entry into B cells via CD21, initiating infection.", "protein": "EBV gp350/220", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "high", "disease": "Burkitt\u2019s lymphoma", "glycan_involvement": "Glycosylation modulates immune recognition and cell tropism.", "mechanism": "Initiates B cell infection, leading to latent transformation and oncogenesis.", "protein": "EBV gp350/220", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "high", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "N-glycosylation affects membrane localization and signaling.", "mechanism": "LMP1 acts as a constitutive receptor, activating NF-\u03baB and promoting cell survival.", "protein": "EBV LMP1", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "medium", "disease": "Kaposi\u2019s sarcoma", "glycan_involvement": "N-glycans required for receptor binding and immune evasion.", "mechanism": "Mediates viral entry into endothelial cells, initiating infection.", "protein": "KSHV gB", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation modulates secretion, antigenicity, and immune escape.", "mechanism": "Chronic HBsAg expression correlates with persistent infection and HCC risk.", "protein": "HBV HBsAg", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7329114" }, { "confidence": "medium", "disease": "Cervical cancer", "glycan_involvement": "Glycosylation influences capsid assembly and host cell binding.", "mechanism": "L1 forms the viral capsid, enabling infection of basal epithelial cells.", "protein": "HPV L1", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "medium", "disease": "Merkel cell carcinoma", "glycan_involvement": "Sialic acid-binding via glycosylated VP1 is essential for cell entry.", "mechanism": "VP1 mediates viral attachment and entry; persistent infection leads to transformation.", "protein": "MCPyV VP1", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "medium", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation modulates epithelial tropism.", "mechanism": "Facilitates EBV infection of epithelial cells, contributing to carcinogenesis.", "protein": "EBV gp350/220", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "medium", "disease": "Primary effusion lymphoma", "glycan_involvement": "N-glycans required for B cell receptor interaction.", "mechanism": "Enables KSHV entry into B cells, leading to latent infection and lymphoma.", "protein": "KSHV gB", "relationship_type": "causal", "source_pmcid": "PMC7329114" }, { "confidence": "high", "disease": "Infectious mononucleosis", "glycan_involvement": "Glycosylation affects antigenicity and immune detection.", "mechanism": "Antibodies to gp350/220 are diagnostic for acute EBV infection.", "protein": "EBV gp350/220", "relationship_type": "biomarker", "source_pmcid": "PMC7329114" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Autoantibodies against collagen II drive joint inflammation and destruction.", "protein": "Collagen type II", "relationship_type": "causal", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation modulates immune response and antigen presentation.", "mechanism": "Autoimmunity against MOG leads to CNS demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation influences peptide binding and T-cell activation.", "mechanism": "Certain HLA-DR alleles confer genetic susceptibility to RA.", "protein": "Human leukocyte antigen (HLA) class II", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "HLA-DR2 allele linked to MS susceptibility.", "protein": "Human leukocyte antigen (HLA) class II", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7329115" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation regulates cell-cell interactions.", "mechanism": "Upregulated in inflamed synovium, mediates leukocyte recruitment.", "protein": "Intercellular adhesion molecule-1 (ICAM-1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7329115" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation essential for ligand binding.", "mechanism": "Promotes leukocyte migration into joints.", "protein": "Vascular cell adhesion molecule-1 (VCAM-1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Fc glycosylation affects effector function and inflammation.", "mechanism": "IgG and complement deposition on myelin mediates demyelination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "IL-6R blockade reduces inflammation in RA.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation modulates integrin-ligand interactions.", "mechanism": "Natalizumab blocks ITGA4 to prevent leukocyte CNS entry.", "protein": "Alpha-4 integrin (ITGA4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7329115" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Sialylation critical for MAG-neuron interactions.", "mechanism": "MAG knockout models show dysmyelination and altered neurotransmission.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "causal/protective", "source_pmcid": "PMC7329115" }, { "confidence": "high", "disease": "Cholera", "glycan_involvement": "Binds GM1 ganglioside (glycan) on host cells for entry; glycosylation critical for function.", "mechanism": "Induces antitoxin and mucosal IgA responses, preventing Vibrio cholerae colonization.", "protein": "Cholera toxin B subunit", "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Elicits neutralizing antibodies; target of mucosal and systemic immunity.", "protein": "Influenza hemagglutinin", "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation required for secretion and immunogenicity.", "mechanism": "Induces IgA and IgG responses; used in mucosal vaccine formulations.", "protein": "Hepatitis B surface antigen", "protein_enriched": { "function": "The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches t", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P03138" }, "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes from immune recognition.", "mechanism": "Target of neutralizing antibodies in mucosal vaccines.", "protein": "HIV gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Glycosylation affects fusion activity and immunogenicity.", "mechanism": "Induces mucosal IgA and systemic IgG; target for vaccine-induced immunity.", "protein": "Respiratory syncytial virus F protein", "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Streptococcal infections", "glycan_involvement": "Glycosylation may affect stability and immune recognition.", "mechanism": "Vaccine antigen induces mucosal and systemic immunity.", "protein": "Streptococcal C5a peptidase", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q99ZP0" }, "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Plague", "glycan_involvement": "Glycosylation enhances immunogenicity.", "mechanism": "Induces humoral and Th1/Th2 responses in mucosal vaccines.", "protein": "Yersinia pestis F1-V antigen", "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Chlamydia infection", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Stimulates CD4+ T-cell and antibody responses in mucosal vaccines.", "protein": "Chlamydia trachomatis major outer membrane protein", "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Diphtheria", "glycan_involvement": "Glycosylation affects immunogenicity.", "mechanism": "Induces mucosal and systemic immunity when delivered with ISCOMs.", "protein": "Diphtheria toxoid", "protein_enriched": { "function": "Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to elongation fact", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00587" }, "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "medium", "disease": "Group A Streptococcus infection", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Mucosal vaccines induce IgA and Th1/Th2 responses.", "protein": "Group A Streptococcus M protein", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02949" }, "relationship_type": "protective", "source_pmcid": "PMC7329122" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry into host cells by binding ACE2 receptor.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates infectivity and antigenicity.", "mechanism": "Mediates viral entry into host cells via ACE2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation influences receptor interaction.", "mechanism": "Mediates viral entry via DPP4 receptor.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates spike binding affinity.", "mechanism": "Acts as host cell receptor for SARS-CoV-2 spike protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation affects viral binding.", "mechanism": "Acts as host cell receptor for MERS-CoV spike protein.", "protein": "DPP4", "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector functions.", "mechanism": "Neutralizes virus via convalescent plasma therapy.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7330532" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects stability and mucosal transport.", "mechanism": "Neutralizes virus at mucosal surfaces.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC7330532" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Antibody glycosylation affects therapeutic efficacy.", "mechanism": "Targets spike protein RBD, neutralizes viral entry.", "protein": "Monoclonal antibody CR3014", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7330532" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Antibody glycosylation affects therapeutic efficacy.", "mechanism": "Targets spike protein RBD, synergistically neutralizes virus.", "protein": "Monoclonal antibody CR3022", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7330532" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation may modulate immune activation.", "mechanism": "Triggers cytokine release syndrome leading to ARDS.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7330532" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Binds to sialylated glycan receptors on host cells.", "mechanism": "Mediates viral attachment to host cell sialic acid residues, enabling infection.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7347422" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Acts on sialylated glycans on host cell surface.", "mechanism": "Cleaves sialic acids to facilitate viral release from infected cells.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7347422" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Prevents glycan-mediated viral attachment.", "mechanism": "Elderberry flavonoids and lectins inhibit hemagglutinin binding to host sialic acids, blocking viral entry.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7347422" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Inhibits cleavage of sialylated glycans.", "mechanism": "Elderberry extract blocks neuraminidase activity, inhibiting viral spread.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7347422" }, { "confidence": "medium", "disease": "HIV infection", "glycan_involvement": "gp120 is highly glycosylated; elderberry may disrupt glycan-mediated interactions.", "mechanism": "Elderberry extract reduces HIV infectivity, possibly by interfering with gp120-mediated entry.", "protein": "HIV gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7347422" }, { "confidence": "medium", "disease": "Herpes simplex virus infection", "glycan_involvement": "HSV glycoproteins are glycosylated; inhibition may involve glycan interactions.", "mechanism": "Elderberry flavonoids inhibit HSV-1 infection, likely by interfering with glycoprotein D-mediated entry.", "protein": "Herpes simplex virus glycoprotein D", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7347422" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Competes for sialylated glycan binding sites.", "mechanism": "Lectins bind to sialic acids on host cells, blocking viral hemagglutinin attachment.", "protein": "Lectins (from Sambucus nigra)", "relationship_type": "protective", "source_pmcid": "PMC7347422" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Cytokines are glycoproteins; glycosylation affects stability and secretion.", "mechanism": "Elderberry extract stimulates cytokine production, enhancing immune response.", "protein": "Cytokines (IL-1\u03b2, TNF-\u03b1, IL-6, IL-8, IFN-\u03b3)", "relationship_type": "protective", "source_pmcid": "PMC7347422" }, { "confidence": "low", "disease": "Common cold", "glycan_involvement": "Blocks glycan-mediated viral entry.", "mechanism": "Elderberry components may inhibit hemagglutinin-like proteins in other respiratory viruses.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7347422" }, { "confidence": "low", "disease": "Respiratory syncytial virus infection", "glycan_involvement": "Interferes with glycan-mediated viral entry.", "mechanism": "Lectins may block viral attachment to host glycan receptors.", "protein": "Lectins (from Sambucus nigra)", "relationship_type": "protective", "source_pmcid": "PMC7347422" }, { "confidence": "high", "disease": "Feline leukemia", "glycan_involvement": "Glycosylation of gp70 is essential for immunogenicity and viral entry.", "mechanism": "gp70 is the main antigen in FeLV vaccines, inducing protective immunity.", "protein": "Feline leukemia virus envelope glycoprotein gp70", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348621" }, { "confidence": "high", "disease": "Feline infectious peritonitis (FIP)", "glycan_involvement": "Glycosylation modulates immune recognition and antibody-dependent enhancement.", "mechanism": "Spike protein mediates viral entry and is the main target of neutralizing antibodies.", "protein": "Feline coronavirus spike protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "high", "disease": "Effusive FIP", "glycan_involvement": "Glycosylation affects antibody binding and enhancement.", "mechanism": "Antibodies to spike protein can enhance macrophage infection, worsening disease.", "protein": "Feline coronavirus spike protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "medium", "disease": "Glomerulonephritis (FIP-associated)", "glycan_involvement": "Glycosylation influences immune complex formation.", "mechanism": "Immune complexes containing spike protein deposit in glomeruli, causing nephritis.", "protein": "Feline coronavirus spike protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "medium", "disease": "Feline calicivirus disease", "glycan_involvement": "Glycosylation affects antigenicity and immune response.", "mechanism": "Capsid glycoprotein is the main antigen in vaccines, inducing neutralizing antibodies.", "protein": "Feline calicivirus capsid glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348621" }, { "confidence": "medium", "disease": "Feline herpesvirus infection", "glycan_involvement": "Glycosylation modulates immune evasion and antigenicity.", "mechanism": "Envelope glycoproteins are vaccine antigens, inducing protective immunity.", "protein": "Feline herpesvirus envelope glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348621" }, { "confidence": "high", "disease": "Injection-site sarcoma", "glycan_involvement": "PDGF is a glycoprotein; glycosylation is required for secretion and function.", "mechanism": "PDGF and its receptor are overexpressed in sarcomas, driving fibroblast proliferation.", "protein": "PDGF", "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "high", "disease": "Injection-site sarcoma", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Mutated p53 found in up to 60% of sarcomas, leading to loss of cell cycle control.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "medium", "disease": "Injection-site sarcoma", "glycan_involvement": "Indirect; NF-\u03baB regulates expression of glycoproteins involved in inflammation.", "mechanism": "NF-\u03baB activation promotes tumorigenesis via inflammation and cell survival.", "protein": "NF-\u03baB", "protein_enriched": { "function": "NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to", "gene_name": "NFKB1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P19838" }, "relationship_type": "causal", "source_pmcid": "PMC7348621" }, { "confidence": "medium", "disease": "Feline leukemia", "glycan_involvement": "Glycosylation affects immunogenicity and membrane fusion.", "mechanism": "Included in recombinant vaccines to enhance immune response.", "protein": "Feline leukemia virus transmembrane protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348621" }, { "confidence": "high", "disease": "Classical swine fever", "glycan_involvement": "Glycosylation of E2 is essential for immunogenicity and antigenicity.", "mechanism": "E2 is the immunodominant protective antigen; vaccines based on E2 induce protective immunity.", "protein": "Envelope glycoprotein E2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Porcine epidemic diarrhea", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "S protein mediates viral entry and is the main target of neutralizing antibodies in vaccines.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation required for proper folding and immune detection.", "mechanism": "gE-deleted vaccines enable DIVA strategy; anti-gE antibodies indicate wild-type infection.", "protein": "Glycoprotein E (gE)", "protein_enriched": { "function": "Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of cla", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P04494" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Pseudorabies (Aujeszky\u2019s disease)", "glycan_involvement": "Glycosylation influences immunogenicity.", "mechanism": "gI deletion in vaccines increases safety and enables DIVA diagnostics.", "protein": "Glycoprotein I (gI)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Porcine circovirus disease", "glycan_involvement": "Glycosylation may affect immunogenicity and vaccine efficacy.", "mechanism": "Capsid protein is the main antigen in subunit and chimeric vaccines; induces neutralizing antibodies.", "protein": "Capsid protein", "protein_enriched": { "function": "Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers ", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 6, "glytoucan_ids": [], "uniprot_id": "P03315" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Swine influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune escape.", "mechanism": "HA is the major target of neutralizing antibodies; included in all vaccines.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "medium", "disease": "Porcine pleuropneumonia", "glycan_involvement": "Glycosylation may influence toxin activity and immunogenicity.", "mechanism": "Apx toxins are central to pathogenesis; vaccines containing inactivated Apx toxins reduce disease severity.", "protein": "Apx toxins (I, II, III)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "medium", "disease": "Porcine pleuropneumonia", "glycan_involvement": "Likely glycosylated, affecting immune recognition.", "mechanism": "Used in combination vaccines to enhance protection.", "protein": "Outer membrane protein (42 kDa)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "medium", "disease": "Atrophic rhinitis", "glycan_involvement": "Glycosylation may affect toxin structure and immunogenicity.", "mechanism": "Toxin is the main virulence factor; toxoid vaccines are highly protective.", "protein": "P. multocida toxin", "protein_enriched": { "function": "Metalloprotease, specifically cleaves on the N-terminal side of aspartyl, glutamyl and cysteic acid residues", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9R4J4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "medium", "disease": "Boar taint", "glycan_involvement": "Protein carrier may be glycosylated, enhancing immunogenicity.", "mechanism": "Induces anti-GnRH antibodies, blocking hormone activity and preventing boar taint.", "protein": "GnRH-protein conjugate", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348622" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "Autoantibodies against MOG implicated in demyelination; molecular mimicry with dietary proteins may trigger immune response.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IgG is N-glycosylated; glycosylation affects effector function and immune complex formation.", "mechanism": "Oligoclonal IgG bands in CSF are diagnostic for MS, indicating intrathecal antibody production.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7348625" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Complement proteins are glycosylated; glycosylation modulates activation and clearance.", "mechanism": "Complement deposition in MS lesions mediates antibody-dependent demyelination.", "protein": "Complement proteins", "relationship_type": "causal", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IFN-\u03b2 is glycosylated; glycosylation affects stability and bioactivity.", "mechanism": "IFN-\u03b2 reduces relapse rates and modulates immune response in MS.", "protein": "Interferon beta (IFN-\u03b2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348625" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD52 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Targeted by alemtuzumab to deplete immune cells and reduce MS activity.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Integrins are glycosylated; glycosylation modulates ligand binding and trafficking.", "mechanism": "Targeted by natalizumab to block immune cell migration into CNS.", "protein": "Alpha-4 integrin (ITGA4)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348625" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MMP-9 is glycosylated; glycosylation affects secretion and activity.", "mechanism": "Elevated MMP-9 promotes immune cell migration into CNS by disrupting blood-brain barrier.", "protein": "Matrix metallopeptidase-9 (MMP-9)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "HLA-DR molecules are glycosylated; glycosylation influences peptide presentation.", "mechanism": "Certain HLA-DRB1 alleles increase genetic susceptibility to MS.", "protein": "Human leukocyte antigen DRB1 (HLA-DRB1)", "relationship_type": "causal/risk factor", "source_pmcid": "PMC7348625" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "CD25 is glycosylated; glycosylation affects receptor function.", "mechanism": "Targeted by daclizumab (withdrawn) to modulate T cell activation.", "protein": "Interleukin-2 receptor alpha (CD25)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IgG glycosylation may influence immune complex formation and persistence.", "mechanism": "Presence in CSF is diagnostic for MS, reflecting chronic CNS inflammation.", "protein": "Oligoclonal bands (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC7348625" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation modulates host interaction and antigenicity.", "mechanism": "S protein binds ACE2, facilitating viral entry and infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation influences receptor binding and immune recognition.", "mechanism": "S protein mediates host cell entry via DPP4 receptor.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein function and virulence.", "mechanism": "E protein is involved in viral assembly and pathogenesis.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may impact viral morphogenesis.", "mechanism": "M protein shapes viral envelope and assembly.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates S protein binding affinity.", "mechanism": "ACE2 is the host receptor for S protein; blocking interaction can prevent infection.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7352094" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation affects antibody effector functions.", "mechanism": "Convalescent plasma immunoglobulins neutralize virus and improve survival.", "protein": "Immunoglobulins", "relationship_type": "protective", "source_pmcid": "PMC7352094" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may affect enzyme activity.", "mechanism": "Essential for viral polyprotein processing; inhibition blocks replication.", "protein": "Papain-like protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7352094" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation status may influence drug binding.", "mechanism": "Key for viral protein maturation; target for antiviral drugs.", "protein": "3-chymotrypsin-like protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7352094" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome", "glycan_involvement": "Glycosylation may modulate immune response and severity.", "mechanism": "S protein-mediated infection can trigger severe lung inflammation.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7352094" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Truncated O-glycans (Tn, sialyl-Tn) on MUC1 serve as cancer-specific antigens.", "mechanism": "Altered glycosylation of MUC1 generates tumor-associated epitopes recognized by specific antibodies.", "protein": "MUC1", "protein_enriched": { "function": "The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack", "gene_name": "MUC1", "glycan_count": 42, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57321FI", "G10773YW", "G20210JR", "G23984SE", "G63381RX", "G92062TF", "G49108TO", "G27391WQ", "G58001LT", "G29068FM", "G43417UB", "G53434XO", "G00031MO", "G00033MO", "G01614ZM", "G07677VL", "G18519LX", "G18946TX", "G19399OS", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G38887TM", "G42665KV", "G47325XO", "G49582PC", "G56682BC", "G58272ZE", "G60145BJ", "G60890ZT", "G63110FE", "G63628AV", "G64973KT", "G65562ZE", "G74722FL", "G76163CP", "G78315FS", "G80903UK", "G81006GJ", "G94435QH", "G97263AV" ], "uniprot_id": "P15941" }, "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "high", "disease": "Colorectal cancer", "glycan_involvement": "Tumor-associated Tn and sialyl-Tn glycans on MUC4 are recognized by IgG/IgA antibodies.", "mechanism": "Altered glycosylation of MUC4 produces cancer-associated glycopeptide epitopes.", "protein": "MUC4", "protein_enriched": { "function": "Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces (PubMed:10880978). These g", "gene_name": "MUC4", "glycan_count": 17, "glycosylation_sites_count": 547, "glytoucan_ids": [ "G57321FI", "G00031MO", "G26493RP", "G29931IJ", "G31685JQ", "G32550BI", "G42665KV", "G47325XO", "G49108TO", "G49582PC", "G58272ZE", "G60145BJ", "G63628AV", "G64973KT", "G74722FL", "G76163CP", "G94435QH" ], "uniprot_id": "Q99102" }, "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Aberrant glycosylation leads to Globo H expression on cancer cells.", "mechanism": "Globo H is overexpressed on tumor cells and elicits antibody responses; used in vaccine development.", "protein": "Globo H", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7411385" }, { "confidence": "high", "disease": "Hepatocellular carcinoma", "glycan_involvement": "Specific N-glycosylation pattern (core fucosylation) distinguishes AFP-L3.", "mechanism": "AFP-L3 glycoform is elevated in HCC and can differentiate HCC from chronic hepatitis B.", "protein": "AFP-L3 (alpha-fetoprotein fraction L3)", "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "GPI anchor pentasaccharide is the minimal epitope for antibody binding.", "mechanism": "Anti-GPI antibodies are elevated in malaria patients and reflect exposure.", "protein": "GPI (glycosylphosphatidylinositol)", "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "medium", "disease": "Anthrax", "glycan_involvement": "Terminal anthrose and rhamnose residues form vaccine targets.", "mechanism": "Anthrose-containing oligosaccharides on BC1A are immunogenic and targeted by vaccine-induced antibodies.", "protein": "BC1A glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7411385" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "Man8/Man9 structures are critical for antibody recognition and neutralization.", "mechanism": "Broadly neutralizing antibody 2G12 binds high mannose N-glycans on HIV envelope glycoproteins.", "protein": "High mannose N-glycans", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7411385" }, { "confidence": "medium", "disease": "SARS-CoV vaccine-induced autoimmunity", "glycan_involvement": "Loss of sialic acid exposes glycan epitopes recognized by autoantibodies.", "mechanism": "SARS-CoV vaccine induces IgG antibodies to asialo-orosomucoid, indicating glycan-dependent autoimmunity.", "protein": "Asialo-orosomucoid", "relationship_type": "biomarker/causal", "source_pmcid": "PMC7411385" }, { "confidence": "medium", "disease": "Lyme disease", "glycan_involvement": "Disialylated ganglioside structure is the antibody target.", "mechanism": "Elevated anti-GD1b-lactone antibodies in Lyme disease patients serve as diagnostic markers.", "protein": "Ganglioside GD1b-lactone", "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "medium", "disease": "Systemic sclerosis", "glycan_involvement": "Sulfation of LacNAc generates immunogenic epitopes.", "mechanism": "Antibodies to 4S-LacNAc are associated with systemic sclerosis and pulmonary hypertension.", "protein": "4-sulfated LacNAc", "relationship_type": "biomarker", "source_pmcid": "PMC7411385" }, { "confidence": "high", "disease": "Acute Liver Failure (ALF)", "glycan_involvement": "N-glycosylation required for secretion and stability; impaired glycosylation may further reduce activity.", "mechanism": "Reduced hepatic synthesis leads to decreased prothrombin activity, indicating liver synthetic dysfunction.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker", "source_pmcid": "PMC7418529" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "N-glycosylation essential for TPO secretion and function.", "mechanism": "Reduced hepatic synthesis of TPO leads to decreased platelet production.", "protein": "Thrombopoietin (TPO)", "protein_enriched": { "function": "Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major ", "gene_name": "THPO", "glycan_count": 32, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G00227RN", "G00800WJ", "G01817YC", "G14389GM", "G16265MV", "G17689DH", "G44444MB", "G47058MH", "G56501FP", "G57789QC", "G90352XZ", "G94531EZ", "G00031MO", "G01614ZM", "G11629QQ", "G15169WU", "G19075PM", "G22310AV", "G29931IJ", "G39595FH", "G57321FI", "G57581QG", "G64394MX", "G65562ZE", "G69834CE", "G72667IM", "G74722FL", "G81006GJ", "G81263BG", "G84452RH", "G87015RU", "G96170OK" ], "uniprot_id": "P40225" }, "relationship_type": "causal", "source_pmcid": "PMC7418529" }, { "confidence": "medium", "disease": "Coagulation Dysfunction", "glycan_involvement": "N-glycosylation critical for surface expression and function.", "mechanism": "Reduced expression impairs platelet aggregation and clot retraction.", "protein": "Platelet glycoprotein GPIb-IX complex", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7418529" }, { "confidence": "high", "disease": "Coagulation Dysfunction", "glycan_involvement": "N-glycosylation required for secretion and activity of factors II, VII, IX, X, etc.", "mechanism": "Liver failure reduces synthesis of multiple glycoprotein coagulation factors, leading to bleeding.", "protein": "Coagulation factors (general)", "relationship_type": "causal", "source_pmcid": "PMC7418529" }, { "confidence": "medium", "disease": "Chronic Liver Failure (CLF)", "glycan_involvement": "N-glycosylation affects stability and half-life.", "mechanism": "Decreased synthesis reflects impaired liver function.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7418529" }, { "confidence": "medium", "disease": "Infection (secondary to liver failure)", "glycan_involvement": "N-glycosylation modulates effector function and clearance.", "mechanism": "Altered synthesis and glycosylation contribute to immune dysfunction and susceptibility to infection.", "protein": "Immunoglobulins", "relationship_type": "causal", "source_pmcid": "PMC7418529" }, { "confidence": "medium", "disease": "Acute-on-Chronic Liver Failure (ACLF)", "glycan_involvement": "N-glycosylation required for secretion and iron binding.", "mechanism": "Decreased synthesis indicates impaired liver function.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7418529" }, { "confidence": "medium", "disease": "Chronic Liver Failure (CLF)", "glycan_involvement": "N-glycosylation required for secretion; misglycosylation leads to retention and liver injury.", "mechanism": "Reduced synthesis reflects hepatocyte dysfunction.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. 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"G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC7418529" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Spike protein is heavily glycosylated, which affects receptor binding and immune evasion.", "mechanism": "Spike glycoprotein binds to ACE2 to mediate viral entry into host cells.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7430191" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation may influence spike binding.", "mechanism": "ACE2 acts as the host receptor for SARS-CoV-2 spike glycoprotein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7430191" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Variant near glycosylation hotspots may alter glycan-mediated interactions.", "mechanism": "S331F variant increases affinity for spike glycoprotein, potentially increasing susceptibility.", "protein": "ACE2 (S331F variant)", "relationship_type": "susceptibility/biomarker", "source_pmcid": "PMC7430191" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Variant may alter local glycan structure or conformation, reducing viral binding.", "mechanism": "V485L variant reduces spike glycoprotein binding, possibly conferring natural resistance.", "protein": "ACE2 (V485L variant)", "relationship_type": "protective", "source_pmcid": "PMC7430191" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Some variants may affect glycosylation sites or local structure.", "mechanism": "These variants increase susceptibility by enhancing spike binding.", "protein": "ACE2 (other variants: S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P, H378R)", "relationship_type": "susceptibility/biomarker", "source_pmcid": "PMC7430191" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "May affect glycan presentation or receptor conformation.", "mechanism": "These variants reduce spike binding, potentially lowering susceptibility.", "protein": "ACE2 (other variants: K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L, D509Y)", "relationship_type": "protective", "source_pmcid": "PMC7430191" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect ACE2 stability and function.", "mechanism": "ACE2 polymorphisms are associated with hypertension symptoms.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7430191" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation status may influence therapeutic targeting.", "mechanism": "ACE2 is a potential target for therapies to block viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7430191" }, { "confidence": "high", "disease": "Plague (Bubonic, Septicemic, Pneumonic)", "glycan_involvement": "Biofilm matrix contains glycoproteins essential for adhesion and blockage.", "mechanism": "Biofilm formation in flea gut enables transmission to humans.", "protein": "Yersinia pestis biofilm matrix proteins", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "medium", "disease": "Plague (Bubonic, Septicemic, Pneumonic)", "glycan_involvement": "Glycosylation may affect toxin stability and activity.", "mechanism": "Ymt enables survival of Y. pestis in flea vector.", "protein": "Yersinia murine toxin (Ymt)", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Histamine is not a glycoprotein but interacts with glycosylated immune receptors.", "mechanism": "Histamine release mediates immune response and inflammation after mosquito bite.", "protein": "Histamine", "relationship_type": "biomarker", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Malaria", "glycan_involvement": "Glycosylation critical for immune evasion and anticoagulant activity.", "mechanism": "Salivary glycoproteins modulate host immune response and facilitate parasite entry.", "protein": "Mosquito salivary glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Malaria", "glycan_involvement": "N-glycosylation required for host cell recognition.", "mechanism": "Surface glycoproteins mediate hepatocyte invasion.", "protein": "Plasmodium sporozoite surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation modulates infectivity and antibody recognition.", "mechanism": "Envelope glycoprotein mediates host cell entry and immune evasion.", "protein": "Dengue virus envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "West Nile Virus infection", "glycan_involvement": "N-glycosylation affects neuroinvasiveness and immune response.", "mechanism": "Envelope glycoprotein enables viral entry into host cells.", "protein": "West Nile virus envelope glycoprotein", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9Q6Q1" }, "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Chikungunya fever", "glycan_involvement": "Glycosylation influences viral infectivity.", "mechanism": "Envelope glycoprotein mediates viral attachment and fusion.", "protein": "Chikungunya virus envelope glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Japanese encephalitis", "glycan_involvement": "N-glycosylation modulates neurotropism.", "mechanism": "Envelope glycoprotein required for host cell entry.", "protein": "Japanese encephalitis virus envelope glycoprotein", "protein_enriched": { "function": "Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome pene", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "P27395" }, "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "medium", "disease": "Lymphatic filariasis", "glycan_involvement": "Glycosylation essential for immune evasion.", "mechanism": "Parasite glycoproteins modulate host immune response and facilitate infection.", "protein": "Filariasis parasite glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7442119" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation of VP7 is essential for proper folding and antigenicity.", "mechanism": "VP7 is a major outer capsid glycoprotein defining rotavirus serotypes and mediating host cell entry.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "causal", "source_pmcid": "PMC7455206" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation affects antigenic properties and immune recognition.", "mechanism": "VP7 serotype (G1-G27) is used for epidemiological typing and vaccine design.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "biomarker", "source_pmcid": "PMC7455206" }, { "confidence": "medium", "disease": "Malabsorption syndrome", "glycan_involvement": "NSP4 is glycosylated, which is important for its enterotoxin activity.", "mechanism": "NSP4 acts as a viral enterotoxin, disrupting epithelial function and contributing to diarrhea.", "protein": "NSP4", "protein_enriched": { "function": "Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11194" }, "relationship_type": "causal", "source_pmcid": "PMC7455206" }, { "confidence": "medium", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "VP4 interacts with host cell glycans for attachment; glycosylation may modulate tropism.", "mechanism": "VP4 mediates viral attachment and entry into host cells.", "protein": "VP4", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7455206" }, { "confidence": "high", "disease": "Rotavirus gastroenteritis", "glycan_involvement": "Glycosylation influences immunogenicity and vaccine efficacy.", "mechanism": "VP7 is targeted by neutralizing antibodies induced by vaccines.", "protein": "VP7", "protein_enriched": { "function": "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin", "gene_name": "Ttl", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9QXJ0" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7455206" }, { "confidence": "high", "disease": "IgG4-related disease", "glycan_involvement": "IgG4 glycosylation may affect effector function and immune regulation.", "mechanism": "Tissue infiltration by IgG4-positive plasma cells is a hallmark of disease.", "protein": "IgG4", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG3", "glycan_count": 128, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G57321FI", "G00031MO", "G29931IJ", "G39558MO", "G49582PC", "G74722FL", "G81006GJ", "G29068FM", "G43417UB", "G49108TO", "G03382KH", "G05642HQ", "G06356OH", "G08293MJ", "G10256JP", "G10486CT", "G14994KB", "G22140GZ", "G23432EQ", "G23863VK", "G25987BV", "G31916IQ", "G31936TA", "G33244HE", "G37868ZX", "G39943KJ", "G43157UW", "G45495MK", "G46687AB", "G49874UX", "G50045TK", "G55052CN", "G56903ZB", "G57818FI", "G59937CP", "G61627IG", "G61937QU", "G68318VE", "G72787SB", "G75798PH", "G79568CQ", "G80858MF", "G81295CK", "G83204BU", "G83555HU", "G84452RH", "G91636VS", "G92129PT", "G02030ZB", "G03127AL", "G05724UK", "G05850WN", "G06110VR", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G11870QZ", "G12398HZ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G22310AV", "G23294PN", "G23453IV", "G24835MQ", "G25520XG", "G26403SG", "G27919IH", "G29880MM", "G30159WR", "G33609NS", "G33780DA", "G34730YF", "G36191CD", "G36836GD", "G39188ZX", "G39213VZ", "G42358LZ", "G43694RQ", "G47518TP", "G48414YA", "G50636SI", "G52064IJ", "G52934AK", "G53276NK", "G55220VL", "G56749GV", "G58667NI", "G59471TH", "G60145BJ", "G62831KM", "G64527OM", "G65219TP", "G66538GV", "G66760KM", "G66937TJ", "G69411IG", "G70101JE", "G71013KY", "G71269BI", "G72291OX", "G72667IM", "G72718TT", "G72956NR", "G74724QE", "G75727PF", "G75983OB", "G78059CC", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82463GQ", "G83355KE", "G83461WR", "G84467IZ", "G85767HW", "G86750HK", "G89319AW", "G89993FE", "G91023GB", "G91365ZQ", "G91473PK", "G94854LT" ], "uniprot_id": "P01860" }, "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "high", "disease": "Ligneous conjunctivitis", "glycan_involvement": "Plasminogen is a glycoprotein; glycosylation affects stability and activity.", "mechanism": "Plasminogen deficiency leads to impaired fibrin breakdown and pseudomembrane formation.", "protein": "Plasminogen", "relationship_type": "causal", "source_pmcid": "PMC7463038" }, { "confidence": "high", "disease": "Hereditary angioedema", "glycan_involvement": "C1INH is heavily glycosylated; glycosylation is essential for function.", "mechanism": "Deficiency or dysfunction of C1INH leads to uncontrolled bradykinin production and angioedema.", "protein": "C1 inhibitor (C1INH)", "relationship_type": "causal", "source_pmcid": "PMC7463038" }, { "confidence": "high", "disease": "Alpha-tryptasemia", "glycan_involvement": "Tryptase is glycosylated; glycosylation affects secretion and stability.", "mechanism": "Elevated serum tryptase due to TPSAB1 gene duplication; associated with mast cell activation symptoms.", "protein": "Mast cell tryptase (alpha-tryptase)", "protein_enriched": { "function": "Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P21895" }, "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "medium", "disease": "Asthma-COPD overlap (ACO)", "glycan_involvement": "NGAL is a glycoprotein; glycosylation modulates its immune functions.", "mechanism": "Elevated plasma NGAL distinguishes ACO from asthma and COPD.", "protein": "NGAL", "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "high", "disease": "Asthma", "glycan_involvement": "Periostin is glycosylated; glycosylation affects extracellular matrix interactions.", "mechanism": "Serum periostin correlates with asthma severity and airway remodeling.", "protein": "Periostin", "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "medium", "disease": "Chronic spontaneous urticaria (CSU)", "glycan_involvement": "IgE glycosylation modulates receptor binding and immune activation.", "mechanism": "Autoantibodies against IgE or its receptor detected by autologous serum skin test (ASST) in CSU.", "protein": "IgE", "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "medium", "disease": "Prostate adenoma", "glycan_involvement": "IgM is highly glycosylated; glycosylation affects immune complex formation.", "mechanism": "Serum IgM levels decreased in prostate adenoma compared to controls.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "low", "disease": "Prostate cancer", "glycan_involvement": "IgA glycosylation affects mucosal immunity and stability.", "mechanism": "Serum IgA increased in prostate cancer and adenoma (not statistically significant).", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "medium", "disease": "Prostate cancer", "glycan_involvement": "IgG glycosylation modulates effector function and immune surveillance.", "mechanism": "Serum IgG levels decrease with metastatic progression.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7463038" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding and viral entry.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; soluble ACE2 can block viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "Glycosylation may affect ACE2 stability and function.", "mechanism": "Recombinant soluble ACE2 (hrsACE2) modulates RAAS and may reduce lung injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "PAH", "glycan_involvement": "Not specified.", "mechanism": "hrsACE2 tested in clinical trials for PAH; modulates vascular tone.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "ALI", "glycan_involvement": "Not specified.", "mechanism": "hrsACE2 shown to be safe in ALI patients; modulates RAAS.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "Myocardial Infarction/Dysfunction", "glycan_involvement": "Not specified.", "mechanism": "Elevated sACE2 activity correlates with myocardial pathology.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "Not specified.", "mechanism": "Elevated sACE2 activity associated with GI tract inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Not specified.", "mechanism": "Elevated sACE2 activity observed in cirrhosis.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "Lung Fibrosis", "glycan_involvement": "Not specified.", "mechanism": "ACE2/Ang(1\u20137) axis activation linked to lung injury/fibrosis.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7475728" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may regulate ADAM17 activity.", "mechanism": "ADAM17 mediates ACE2 shedding, influencing viral entry and inflammation.", "protein": "ADAM17 (TACE)", "protein_enriched": { "function": "Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammatio", "gene_name": "ADAM17", "glycan_count": 58, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G29184RN", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G49108TO", "G10819WX", "G25079LO", "G29299MO", "G45395BF", "G57776ZS", "G70101JE", "G70441OD", "G79666IR", "G80075MS", "G86880BF", "G87123QX", "G90659AW", "G02815KT", "G14260UH", "G27058EU", "G28541PG", "G37399XV", "G39188ZX", "G64527OM", "G82463GQ", "G83633GK", "G00912UN", "G10486CT", "G18647XP", "G20210JR", "G23294PN", "G40926MX", "G59626AS", "G60033FS", "G86182NS", "G04657PL", "G06356OH", "G08918WF", "G20425TQ", "G27947YN", "G43769HG", "G44215PV", "G46902YN", "G59536GA", "G65184UU", "G66163OV", "G70619PT", "G72790NZ", "G81263BG", "G86795LJ", "G95133RI", "G96577RX", "G99668VU", "G35029YA", "G48584BU", "G23719VF", "G72787SB" ], "uniprot_id": "P78536" }, "relationship_type": "causal", "source_pmcid": "PMC7475728" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike heavily glycosylated; glycans shield and modulate ACE2 interaction.", "mechanism": "Spike glycoprotein binds ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7475728" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Integrin glycosylation may affect ligand binding and vesicle incorporation.", "mechanism": "\u03b1v\u03b26 integrin in prostate cancer-derived small extracellular vesicles enhances angiogenesis by transferring to endothelial cells and activating pro-angiogenic signaling.", "protein": "\u03b1v\u03b26 integrin", "relationship_type": "causal", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Cancer (general, including pancreatic and prostate)", "glycan_involvement": "Heparan sulfate glycosylation critical for function and EV association.", "mechanism": "Glypican-1 detected on extracellular vesicles from cancer cell lines; used for EV-based cancer detection.", "protein": "Glypican-1", "relationship_type": "biomarker", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Cancer (general)", "glycan_involvement": "PD-L1 glycosylation modulates stability and immune recognition.", "mechanism": "PD-L1 detected on EVs from cancer cell lines; relevant for immune evasion and as a diagnostic marker.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7480431" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "EGF-family glycosylation affects receptor binding and EV sorting.", "mechanism": "Amphiregulin on fibroblast-derived EVs promotes proliferation and stem cell maintenance in CRC organoids.", "protein": "Amphiregulin", "relationship_type": "causal", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Prostate cancer bone metastasis", "glycan_involvement": "TSP1 glycosylation influences ECM interactions.", "mechanism": "PCa exosomes downregulate TSP1 in bone marrow, promoting metastasis; exosomal miR-4443 mediates effect.", "protein": "Thrombospondin-1 (TSP1)", "relationship_type": "causal/protective", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Prostate cancer bone metastasis", "glycan_involvement": "Chondroitin sulfate glycosylation essential for ECM remodeling.", "mechanism": "PCa exosomes upregulate VCAN in bone marrow, facilitating metastatic niche formation.", "protein": "Versican (VCAN)", "relationship_type": "causal", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau O-glycosylation may affect aggregation and EV sorting.", "mechanism": "Tau and phospho-tau T181 detected in plasma EVs; elevated in AD patients.", "protein": "Tau", "protein_enriched": { "function": "Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter", "gene_name": "MAPT", "glycan_count": 2, "glycosylation_sites_count": 16, "glytoucan_ids": [ "G49108TO", "G80920RR" ], "uniprot_id": "P10636" }, "relationship_type": "biomarker", "source_pmcid": "PMC7480431" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "Glycosylation modulates immune interactions and EV targeting.", "mechanism": "CD24 detected on EVs isolated from ovarian cancer samples; used for diagnostic profiling.", "protein": "CD24", "protein_enriched": { "function": "May have a pivotal role in cell differentiation of different cell types. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of", "gene_name": "CD24", "glycan_count": 14, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G43417UB", "G34617SM", "G49874UX", "G62894KT", "G63381RX", "G64527OM", "G70101JE", "G79286RS", "G81263BG", "G82830MN", "G83951ZY", "G86234IN", "G92081HT", "G96577RX" ], "uniprot_id": "P25063" }, "relationship_type": "biomarker", "source_pmcid": "PMC7480431" }, { "confidence": "medium", "disease": "Ovarian cancer", "glycan_involvement": "N-glycosylation regulates receptor function and EV incorporation.", "mechanism": "EGFR detected on EVs from ovarian cancer; relevant for diagnosis and therapy.", "protein": "EGFR", "protein_enriched": { "function": "Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536", "gene_name": "EGFR", "glycan_count": 149, "glycosylation_sites_count": 13, "glytoucan_ids": [ "G59324HL", "G40834TG", "G49108TO", "G83461WR", "G06356OH", "G10488MI", "G27058EU", "G41071NU", "G80920RR", "G90659AW", "G02815KT", "G14972EH", "G25079LO", "G41247ZX", "G42124LM", "G46687AB", "G49874UX", "G87661QW", "G12793SR", "G47518TP", "G48414YA", "G52527GH", "G59536GA", "G66760KM", "G93656SY", "G02886BB", "G05724UK", "G06110VR", "G22768VO", "G31852PQ", "G39188ZX", "G39213VZ", "G52461YB", "G59924QI", "G62765YT", "G64527OM", "G70101JE", "G78750JU", "G81315DD", "G83460ZZ", "G86182NS", "G92050GC", "G96786JM", "G82830MN", "G04657PL", "G08918WF", "G15127JD", "G25451PN", "G43223CG", "G45395BF", "G60177UT", "G70441OD", "G70619PT", "G75983OB", "G83646BJ", "G95177YH", "G33791AF", "G84452RH", "G27915IV", "G37399XV", "G40926MX", "G59626AS", "G82348BZ", "G79666IR", "G80479JV", "G23863VK", "G78059CC", "G00912UN", "G07246CJ", "G08290VR", "G11629QQ", "G22310AV", "G57317CE", "G78790NZ", "G90382BL", "G15169WU", "G57888GL", "G72291OX", "G81263BG", "G01120GS", "G02030ZB", "G03754YM", "G04672QB", "G07041CT", "G07337US", "G08709JB", "G11561RV", "G11911BT", "G12728EY", "G13156PQ", "G16739XK", "G16933JU", "G17689DH", "G20425TQ", "G21737WY", "G22625SJ", "G23340ZN", "G24271GS", "G29501UT", "G40490KT", "G40702WU", "G43402RG", "G43665PB", "G44346CQ", "G44490NG", "G44623TX", "G44660UQ", "G45359RY", "G45560HM", "G51413EV", "G52692IB", "G52880ZN", "G53752TA", "G54505OS", "G55220VL", "G56784JY", "G57504TA", "G57581QG", "G59590OJ", "G60215UL", "G65019XG", "G65635AB", "G66163OV", "G68668TB", "G69834CE", "G69982RY", "G70375MX", "G70822IO", "G71560PC", "G72797UR", "G74859XI", "G77252PU", "G79394LC", "G79556AB", "G79809MM", "G80966KZ", "G82140BL", "G83161QT", "G84330VA", "G84543RP", "G84783XD", "G85098WU", "G85447US", "G86298IX", "G91425YG", "G92073XL", "G94531EZ", "G96914KN", "G97765TT" ], "uniprot_id": "P00533" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Phosphorylation and glycosylation may jointly affect EV sorting.", "mechanism": "Elevated levels in plasma EVs from AD patients; correlates with disease state.", "protein": "Phospho-tau T181", "relationship_type": "biomarker", "source_pmcid": "PMC7480431" }, { "confidence": "high", "disease": "AECHB", "glycan_involvement": "Glycosylation affects stability and serum half-life.", "mechanism": "Serum levels increase significantly in AECHB, indicating liver injury and inflammation.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "high", "disease": "Severe Hepatitis B", "glycan_involvement": "N-glycosylation in S region critical for antigenicity and immune recognition.", "mechanism": "Mutations (e.g., G145R, C138R) in glycosylated regions lead to immune escape and severe hepatitis.", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "causal", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "Glycosylation modulates cell adhesion and immune cell recruitment.", "mechanism": "Genetic variants (R241-E469) associated with increased risk and severity of AECHB.", "protein": "ICAM1", "relationship_type": "biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "high", "disease": "Severe Hepatitis B", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Elevated TNF-\u03b1 correlates with liver inflammation, necrosis, and poor prognosis.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "Glycosylation influences cytokine stability and activity.", "mechanism": "Promoter SNPs and methylation status linked to disease progression and immune regulation.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "Glycosylation modulates chemokine function and cell trafficking.", "mechanism": "Genetic variant (CXCL10-201G/A) associated with AECHB risk and severity.", "protein": "CXCL10 (IP-10)", "relationship_type": "biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "N-glycosylation essential for antigen presentation.", "mechanism": "Certain alleles (DRB1*1001, DRB1*1301/1302) linked to HBV clearance and AECHB susceptibility.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "protective/biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "Glycosylation affects ligand-receptor interaction and apoptotic signaling.", "mechanism": "FasL-844CC genotype increases risk of severe hepatitis via apoptosis induction.", "protein": "Fas ligand (FasL)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "Severe Hepatitis B", "glycan_involvement": "Glycosylation regulates receptor shedding and function.", "mechanism": "Elevated sCD163 reflects macrophage activation and correlates with liver inflammation.", "protein": "sCD163", "relationship_type": "biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "medium", "disease": "AECHB", "glycan_involvement": "Potential glycosylation may affect enzyme activity and stability.", "mechanism": "Promoter methylation status associated with prognosis and severity of hepatitis B.", "protein": "GSTP1", "relationship_type": "biomarker", "source_pmcid": "PMC7498885" }, { "confidence": "high", "disease": "Severe Hepatitis B", "glycan_involvement": "Fibronectin is a glycoprotein; glycosylation is essential for opsonin function.", "mechanism": "Decreased plasma fibronectin correlates with impaired macrophage opsonization, increased infection risk, and mortality.", "protein": "Fibronectin", "protein_enriched": { "function": "Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3593230, PubMed:3900070, PubMed:7989369). Fibronectins are involved in", "gene_name": "FN1", "glycan_count": 275, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G00273SJ", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G02886BB", "G03574QJ", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G08290VR", "G08293MJ", "G08918WF", "G10339FR", "G10486CT", "G10488MI", "G10819WX", "G10846ZT", "G11314AS", "G12341GU", "G14972EH", "G15038BD", "G15664MX", "G16407EV", "G17208MA", "G18647XP", "G20528HD", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G25079LO", "G25418HZ", "G26271XI", "G26330YA", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G28681TP", "G29299MO", "G31852PQ", "G31986NC", "G32788FZ", "G34989PA", "G35253PZ", "G35541EV", "G36379GD", "G37399XV", "G37509XX", "G37868ZX", "G37995HC", "G39446WN", "G40574BA", "G40664HB", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G43769HG", "G45395BF", "G45504EY", "G46503DX", "G46691LC", "G47644PP", "G47737VJ", "G47950XN", "G48414YA", "G50282JC", "G50372IH", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G58954YZ", "G59626AS", "G59924QI", "G60033FS", "G60834IK", "G60923RB", "G61256FT", "G62765YT", "G64409MC", "G65184UU", "G66933CM", "G68318VE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70888PK", "G72747WU", "G72790NZ", "G73291XG", "G73968GN", "G76295SF", "G77547TA", "G79666IR", "G80075MS", "G80223IX", "G80920RR", "G82830MN", "G83460ZZ", "G83555HU", "G83646BJ", "G84452RH", "G84862VB", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86880BF", "G87051GH", "G87123QX", "G87661QW", "G88374WZ", "G90382BL", "G90659AW", "G92050GC", "G92135MA", "G92275SC", "G92597CK", "G93718GY", "G94470IW", "G95177YH", "G95865ZB", "G98611JV", "G99668VU", "G05724UK", "G22625SJ", "G23453IV", "G31916IQ", "G46687AB", "G46902YN", "G49874UX", "G50045TK", "G64527OM", "G70375MX", "G72291OX", "G78790NZ", "G81295CK", "G82592ZH", "G89098OM", "G90093AU", "G39619TI", "G81263BG", "G57321FI", "G43417UB", "G53434XO", "G58001LT", "G29068FM", "G02030ZB", "G03382KH", "G09197ZW", "G10256JP", "G11870QZ", "G11911BT", "G14994KB", "G16175ZV", "G20698EO", "G20706XG", "G23505EP", "G24528MX", "G24954UD", "G25451PN", "G29880MM", "G39471UU", "G47448YK", "G65092SV", "G66621EA", "G70101JE", "G70822IO", "G72398FA", "G72667IM", "G72735IY", "G72787SB", "G74724QE", "G75983OB", "G77669RF", "G83633GK", "G83951ZY", "G87389XI", "G91636VS", "G92551JA", "G02315DX", "G02528FI", "G02628JF", "G06110VR", "G11629QQ", "G15169WU", "G16125XL", "G16136DL", "G20312EM", "G20425TQ", "G26759AS", "G29545VG", "G30970QQ", "G32332VU", "G37412TK", "G37881RL", "G41126SR", "G44215PV", "G46524LG", "G47012YE", "G47518TP", "G48584BU", "G49018RC", "G49906RN", "G49955PK", "G50073PQ", "G51640FO", "G51653BI", "G54612UD", "G56307ZW", "G58087IP", "G58802FE", "G59324HL", "G59536GA", "G59937CP", "G60177UT", "G62595EF", "G62894KT", "G63381RX", "G63980BQ", "G64394MX", "G66163OV", "G66257KQ", "G68490OW", "G68873DS", "G69107AL", "G70696MD", "G72797UR", "G74430RZ", "G78787DI", "G79568CQ", "G80479JV", "G82119TF", "G88891KO", "G92406TI", "G93683YO", "G94854LT", "G96091TT", "G96577RX", "G12313PD", "G14669DU", "G23432EQ", "G33609NS", "G34029GR", "G35029YA", "G49642SA", "G50757KG", "G57818FI", "G60145BJ", "G82463GQ", "G83229XP", "G84349RE", "G05279MG", "G05746XD", "G36191CD", "G78059CC", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02751" }, "relationship_type": "biomarker", "source_pmcid": "PMC7498917" }, { "confidence": "high", "disease": "Severe Hepatitis B", "glycan_involvement": "C3 is a glycoprotein; glycosylation required for stability and function.", "mechanism": "Reduced hepatic synthesis leads to impaired opsonization and increased susceptibility to infection.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Severe Hepatitis B", "glycan_involvement": "C5 is glycosylated; glycosylation affects complement activation.", "mechanism": "Deficiency impairs neutrophil chemotaxis and phagocytosis, increasing infection risk.", "protein": "Complement C5", "relationship_type": "causal", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Intestinal Infection", "glycan_involvement": "IgA glycosylation is critical for mucosal immune function.", "mechanism": "Reduced IgA secretion weakens mucosal immunity, increasing intestinal infection risk.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC7498917" }, { "confidence": "high", "disease": "Spontaneous Bacterial Peritonitis (SBP)", "glycan_involvement": "Albumin is glycosylated; glycosylation may affect stability and function.", "mechanism": "Low albumin (ascites protein <1.0 g/L) correlates with reduced opsonin activity and higher SBP risk.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Coagulopathy/Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Factor VII is glycosylated; glycosylation required for secretion and activity.", "mechanism": "Endotoxin activates Factor VII, triggering intrinsic coagulation and DIC.", "protein": "Coagulation Factor VII", "protein_enriched": { "function": "Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or t", "gene_name": "F7", "glycan_count": 18, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G71142DF", "G84224TW", "G82576YO", "G96881BQ", "G06215XQ", "G08146BT", "G23695IQ", "G35061TJ", "G42358LZ", "G50739NP", "G71527NE", "G75494EI", "G91130VE", "G00912UN", "G08918WF", "G40574BA", "G43669FQ", "G45395BF" ], "uniprot_id": "P08709" }, "relationship_type": "causal", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Coagulopathy/Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Factor V is glycosylated; glycosylation affects function.", "mechanism": "Endotoxin activates Factor VI, contributing to DIC.", "protein": "Coagulation Factor VI (proaccelerin/F5)", "relationship_type": "causal", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Coagulopathy/Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Tissue factor is glycosylated; glycosylation modulates procoagulant activity.", "mechanism": "Hepatocyte damage releases tissue thromboplastin, activating extrinsic coagulation.", "protein": "Tissue Thromboplastin (Tissue Factor)", "relationship_type": "causal", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Severe Hepatitis B", "glycan_involvement": "CD4 is a glycoprotein; glycosylation affects cell surface expression and function.", "mechanism": "Decreased CD4+ T cells indicate impaired adaptive immunity and higher infection risk.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "biomarker", "source_pmcid": "PMC7498917" }, { "confidence": "medium", "disease": "Severe Hepatitis B", "glycan_involvement": "CD8 is glycosylated; glycosylation influences T cell function.", "mechanism": "Decreased activated CD8+ T cells associated with poor outcomes.", "protein": "CD8", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD8A", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P01732" }, "relationship_type": "biomarker", "source_pmcid": "PMC7498917" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "NS1 is glycosylated, which affects its secretion and immunogenicity.", "mechanism": "NS1 is secreted during acute dengue infection and is detectable in blood and saliva.", "protein": "NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes from immune recognition.", "mechanism": "gp120 mediates viral entry by binding CD4 and is a target for neutralizing antibodies.", "protein": "gp120", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "HA mediates viral attachment to host sialic acid receptors; subtype determines host specificity.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Ebola virus disease", "glycan_involvement": "Heavily glycosylated (N- and O-linked); glycans form a shield against antibodies.", "mechanism": "GP is the sole surface protein, mediates cell entry and immune evasion.", "protein": "Ebola virus glycoprotein (GP)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "N-glycosylation affects infectivity and immune recognition.", "mechanism": "E protein mediates viral entry and is a major antigenic determinant.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation is important for secretion and immunogenicity.", "mechanism": "HBsAg is secreted in large amounts during infection and is used for diagnosis.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Heavily N-glycosylated; glycans shield from immune detection.", "mechanism": "E1/E2 mediate viral entry and are targets for neutralizing antibodies.", "protein": "Hepatitis C virus E1/E2", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "N-glycosylation affects enzymatic activity and immune evasion.", "mechanism": "NA cleaves sialic acids to release new virions; target of antiviral drugs.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Glycosylation is required for secretion and stability.", "mechanism": "NS1 is used in diagnostic assays for early detection.", "protein": "Dengue virus 2 NS1 glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycans modulate receptor binding and immune escape.", "mechanism": "gp120 binding to CD4 is essential for HIV infection.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7509950" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "MMP-1 promotes tumor growth and metastasis by degrading extracellular matrix.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "medium", "disease": "Cardiac hypertrophy and heart attack", "glycan_involvement": "Glycosylation modulates enzyme activity.", "mechanism": "MMP-1 overexpression contributes to cardiac tissue remodeling.", "protein": "MMP-1", "protein_enriched": { "function": "Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:1645757, PubMed:2153297, PubMed:2557822). In case of HIV infection, inter", "gene_name": "MMP1", "glycan_count": 48, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G02628JF", "G03382KH", "G08110WX", "G15198VK", "G23863VK", "G25451PN", "G36221RT", "G38349VC", "G44215PV", "G48381WH", "G50757KG", "G52880ZN", "G56284ZY", "G58268WC", "G63381RX", "G64706DG", "G70418MS", "G72667IM", "G76012OT", "G76136FD", "G78059CC", "G82592ZH", "G85196QC", "G85542KD", "G93856AJ", "G95977AE", "G07799LX", "G08293MJ", "G16175ZV", "G22310AV", "G25418HZ", "G27126ED", "G30123TP", "G31615DN", "G49345XT", "G51413EV", "G70696MD", "G72978AW", "G80223IX", "G84452RH", "G88374WZ", "G94826KT", "G17689DH", "G36191CD", "G44444MB", "G47871MN", "G50045TK", "G75983OB" ], "uniprot_id": "P03956" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "Chronic lung diseases", "glycan_involvement": "N-glycosylation required for secretion.", "mechanism": "MMP-2 degrades basement membrane, facilitating tissue damage.", "protein": "MMP-2", "protein_enriched": { "function": "Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque ruptur", "gene_name": "MMP2", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G29068FM", "G43417UB" ], "uniprot_id": "P08253" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation influences substrate specificity.", "mechanism": "MMP-3 degrades cartilage matrix, promoting joint destruction.", "protein": "MMP-3", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "medium", "disease": "Impaired lung and intestinal immunity", "glycan_involvement": "Glycosylation affects protein folding and secretion.", "mechanism": "MMP-7 degrades host defense proteins, weakening mucosal immunity.", "protein": "MMP-7", "protein_enriched": { "function": "Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase", "gene_name": "MMP7", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P09237" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "Viral lung/pulmonary infections", "glycan_involvement": "N-glycosylation required for secretion and activity.", "mechanism": "MMP-9 promotes inflammation and tissue damage during infection.", "protein": "MMP-9", "protein_enriched": { "function": "Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (PubMed:12879005, PubMed:1480034, PubMed:2551898). Could play a role i", "gene_name": "MMP9", "glycan_count": 39, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G08918WF", "G27058EU", "G45395BF", "G48414YA", "G04657PL", "G31852PQ", "G62765YT", "G70619PT", "G80920RR", "G83460ZZ", "G00031MO", "G01614ZM", "G05380VG", "G14994KB", "G26700PN", "G29931IJ", "G30443NG", "G31916IQ", "G32652KI", "G46687AB", "G46748BU", "G47681UP", "G49854OS", "G53435KM", "G56682BC", "G60145BJ", "G60734PM", "G60890ZT", "G63628AV", "G63794QO", "G64973KT", "G65124UZ", "G65562ZE", "G74038AG", "G74722FL", "G81006GJ", "G81541IU", "G94854LT" ], "uniprot_id": "P14780" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "medium", "disease": "Atherosclerosis and emphysema", "glycan_involvement": "Glycosylation modulates enzyme stability.", "mechanism": "MMP-12 degrades elastin, contributing to vascular and lung pathology.", "protein": "MMP-12", "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "Osteoarthritis and rheumatoid arthritis", "glycan_involvement": "Glycosylation affects secretion and activity.", "mechanism": "MMP-13 degrades type II collagen in cartilage.", "protein": "MMP-13", "protein_enriched": { "function": "Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III colla", "gene_name": "MMP13", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P45452" }, "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "medium", "disease": "Hepatocellular carcinoma", "glycan_involvement": "N-glycosylation required for cell surface localization.", "mechanism": "MMP-14 promotes tumor invasion and metastasis.", "protein": "MMP-14", "relationship_type": "causal", "source_pmcid": "PMC7538275" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and serum half-life.", "mechanism": "CRP is elevated in response to inflammation and correlates with disease severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Procalcitonin is glycosylated, which may affect its secretion and detection.", "mechanism": "Elevated procalcitonin indicates severe infection and possible bacterial co-infection.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "medium", "disease": "Cardiac injury", "glycan_involvement": "Glycosylation modulates pro-BNP stability and bioactivity.", "mechanism": "Elevated pro-BNP reflects cardiac stress and is associated with worse outcomes in COVID-19.", "protein": "N-terminal pro-brain natriuretic peptide (pro-BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Ferritin is glycosylated; glycan structures may influence immune recognition.", "mechanism": "High ferritin reflects hyperinflammation and is associated with severe disease.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects its clearance.", "mechanism": "Elevated D-dimer indicates increased fibrin degradation and risk of thrombosis in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "high", "disease": "Severe pneumonia", "glycan_involvement": "Glycosylation may modulate CRP's interaction with immune cells.", "mechanism": "High CRP levels are associated with severe pulmonary involvement.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation affects procalcitonin's serum levels.", "mechanism": "Procalcitonin is elevated in systemic inflammatory response and sepsis.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Spike protein mediates viral entry into host cells.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7543034" }, { "confidence": "medium", "disease": "Mortality in older adults", "glycan_involvement": "Glycosylation influences pro-BNP's diagnostic accuracy.", "mechanism": "Elevated pro-BNP is associated with increased mortality risk.", "protein": "N-terminal pro-brain natriuretic peptide (pro-BNP)", "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "high", "disease": "Mortality in older adults", "glycan_involvement": "Glycosylation affects D-dimer's half-life and detection.", "mechanism": "High D-dimer is linked to increased mortality in older COVID-19 patients.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7543034" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2, causing infection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7543042" }, { "confidence": "high", "disease": "Cystic Fibrosis (CF)", "glycan_involvement": "Glycosylation stabilizes enzyme and affects pharmacokinetics.", "mechanism": "Cleaves extracellular DNA in mucus, reducing viscosity and improving clearance.", "protein": "Dornase-alfa (human DNase I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect delivery and stability in lungs.", "mechanism": "Proposed to reduce mucus viscosity and potentially disrupt viral attachment.", "protein": "Dornase-alfa (human DNase I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Binds SARS-CoV-2 spike glycoprotein, potentially inhibiting viral entry.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "high", "disease": "COPD", "glycan_involvement": "N-glycosylation critical for secretion and activity.", "mechanism": "Inhibits neutrophil elastase, protecting lung tissue.", "protein": "Alpha-1-antitrypsin (AAT)", "relationship_type": "protective", "source_pmcid": "PMC7543042" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function and half-life.", "mechanism": "Binds SARS-CoV-2 spike glycoprotein, blocking viral attachment.", "protein": "Human neutralizing S230 light chain antibody (mAb)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "medium", "disease": "Cystic Fibrosis (CF)", "glycan_involvement": "Glycosylation may affect secretion and stability.", "mechanism": "Inhibits ENaC, regulates airway hydration, improves mucociliary clearance.", "protein": "SPLUNC1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence airway persistence.", "mechanism": "Proposed to improve airway hydration and reduce infection risk.", "protein": "SPLUNC1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects spike binding affinity.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2 spike glycoprotein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7543042" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Fc glycosylation modulates antibody function.", "mechanism": "Binds SARS-CoV spike protein, neutralizing virus.", "protein": "Human neutralizing S230 light chain antibody (mAb)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7543042" }, { "confidence": "high", "disease": "Autism Spectrum Disorder", "glycan_involvement": "Reelin is a large secreted glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "Reelin controls neural migration and synaptic signaling; mutations impair social behavior in zebrafish models.", "protein": "Reelin", "protein_enriched": { "function": "Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment", "gene_name": "RELN", "glycan_count": 21, "glycosylation_sites_count": 19, "glytoucan_ids": [ "G48414YA", "G56784JY", "G57321FI", "G29068FM", "G43417UB", "G52131KU", "G10019LZ", "G22310AV", "G37881RL", "G38663NM", "G47518TP", "G57888GL", "G62461SM", "G62765YT", "G80920RR", "G23505EP", "G84862VB", "G85282JO", "G87389XI", "G31916IQ", "G49108TO" ], "uniprot_id": "P78509" }, "relationship_type": "causal", "source_pmcid": "PMC7545776" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, which modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2 receptor on host cells.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects Spike binding affinity and viral entry efficiency.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2, enabling infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TMPRSS2 is glycosylated, which may influence its protease activity and localization.", "mechanism": "TMPRSS2 primes Spike glycoprotein for fusion and entry into host cells.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "Pre-implantation embryo infection", "glycan_involvement": "Glycosylation of Spike is essential for receptor interaction and infectivity.", "mechanism": "Spike glycoprotein enables SARS-CoV-2 entry into human pre-implantation embryo cells via ACE2.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "Pre-implantation embryo infection", "glycan_involvement": "ACE2 glycosylation may modulate susceptibility of embryo cells to infection.", "mechanism": "Embryonic ACE2 expression allows SARS-CoV-2 entry and potential infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Spike glycosylation affects receptor binding and immune recognition.", "mechanism": "SARS-CoV-1 Spike mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "SARS-CoV-1 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "medium", "disease": "Pre-implantation embryo infection", "glycan_involvement": "Glycosylation is required for functional receptor interaction.", "mechanism": "SARS-CoV-1 Spike enables entry into embryo cells expressing ACE2.", "protein": "SARS-CoV-1 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Spike glycosylation modulates DPP4 binding and immune evasion.", "mechanism": "MERS-CoV Spike mediates viral entry via DPP4 receptor.", "protein": "MERS-CoV Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "DPP4 glycosylation influences receptor function and viral binding.", "mechanism": "DPP4 acts as the entry receptor for MERS-CoV.", "protein": "Dipeptidyl Peptidase IV (DPP4)", "relationship_type": "causal", "source_pmcid": "PMC7548784" }, { "confidence": "medium", "disease": "Pre-implantation embryo infection", "glycan_involvement": "Absence of DPP4 glycosylation prevents MERS-CoV infection.", "mechanism": "Embryos lacking DPP4 expression are not permissive to MERS-CoV entry.", "protein": "MERS-CoV Spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC7548784" }, { "confidence": "high", "disease": "Hendra Virus Infection", "glycan_involvement": "Glycosylation required for proper folding and immunogenicity.", "mechanism": "Vaccine based on recombinant G glycoprotein induces protective immunity in animal models.", "protein": "Envelope glycoprotein (G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation influences antigenicity and immune recognition.", "mechanism": "AAV vector vaccines encoding E2 glycoprotein elicit humoral immune responses.", "protein": "E2 glycoprotein", "protein_enriched": { "function": "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A", "gene_name": "", "glycan_count": 14, "glycosylation_sites_count": 15, "glytoucan_ids": [ "G02815KT", "G28681TP", "G31852PQ", "G41247ZX", "G62765YT", "G80920RR", "G92050GC", "G57317CE", "G80475RE", "G20956ZV", "G25987BV", "G58087IP", "G59324HL", "G83460ZZ" ], "uniprot_id": "P27958" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "high", "disease": "Ebola Virus Disease", "glycan_involvement": "Glycosylation critical for antigenicity and vaccine efficacy.", "mechanism": "Adenovirus and MVA vector vaccines expressing Ebola GP induce protective immunity.", "protein": "GP (glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation affects immunogenicity.", "mechanism": "Adenovirus vector vaccines expressing rabies GP induce immune protection.", "protein": "GP (glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "AAV and adenovirus vector vaccines expressing E glycoprotein induce protective immunity.", "protein": "E (envelope glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Glycosylation may affect protein folding and immunogenicity.", "mechanism": "Adenovirus vector vaccines expressing prM and E proteins induce immune responses.", "protein": "prM (pre-membrane glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation influences antigenicity and immune escape.", "mechanism": "Adenovirus and recombinant protein vaccines expressing HA induce protective immunity.", "protein": "HA (hemagglutinin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation shields epitopes, modulating immune recognition.", "mechanism": "Adenovirus and poxvirus vector vaccines expressing Env induce immune responses.", "protein": "Env (envelope glycoprotein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation required for immunogenicity.", "mechanism": "Adenovirus vector vaccines expressing rabies G glycoprotein induce protective immunity.", "protein": "Envelope glycoprotein (G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7564847" }, { "confidence": "high", "disease": "HPV Infection", "glycan_involvement": "Glycosylation affects VLP assembly and immunogenicity.", "mechanism": "VLP vaccines based on L1 glycoprotein induce strong protective immunity.", "protein": "Envelope glycoprotein (L1)", "relationship_type": "protective", "source_pmcid": "PMC7564847" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 receptor.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "medium", "disease": "Splenic abscess", "glycan_involvement": "Glycosylation affects S protein stability and tissue tropism.", "mechanism": "Direct viral invasion of spleen via S protein-ACE2 interaction may cause necrosis and predispose to abscess.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "Glycosylation influences S protein binding to intestinal ACE2.", "mechanism": "S protein binds ACE2 on enterocytes, leading to intestinal inflammation and diarrhea.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates S protein binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; its distribution determines organ susceptibility.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7574444" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "Glycosylation may affect ACE2 stability and localization.", "mechanism": "ACE2 regulates intestinal inflammation; viral binding disrupts function, causing diarrhea.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "medium", "disease": "Splenic abscess", "glycan_involvement": "Glycosylation may influence ACE2 tissue distribution.", "mechanism": "ACE2 expression in spleen enables viral entry, contributing to splenic necrosis and abscess.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP indicates systemic inflammation and sepsis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7574444" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "S protein glycosylation may affect vascular tropism.", "mechanism": "COVID-19 infection increases risk of coagulopathy and embolism, possibly via endothelial ACE2 targeting.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7574444" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "GAC contains a polyrhamnose backbone with GlcNAc side chains.", "mechanism": "GAC is the main surface antigen used for identification of Strep A.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "biomarker", "source_pmcid": "PMC7618470" }, { "confidence": "medium", "disease": "Rheumatic heart disease", "glycan_involvement": "GlcNAc side chain is immunodominant and implicated in cross-reactivity.", "mechanism": "Antibodies against GAC (especially GlcNAc side chain) may cross-react with human cardiac tissue, contributing to autoimmune sequelae.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "causal", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "Polyrhamnose backbone is the antigenic target.", "mechanism": "RhaPS is conserved across all Strep A serotypes and is targeted by vaccine-induced antibodies.", "protein": "Rhamnose Polysaccharide (RhaPS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Streptococcus dysgalactiae subsp. equisimilis infection", "glycan_involvement": "RhaPS backbone is present in SDSE_gac isolates.", "mechanism": "Emerging SDSE strains express GAC with RhaPS backbone, making them susceptible to RhaPS-targeted antibodies.", "protein": "Rhamnose Polysaccharide (RhaPS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Streptococcal pharyngitis", "glycan_involvement": "Antibodies target GAC glycan structures.", "mechanism": "High-titre anti-GAC antibodies correlate with protection against throat colonisation.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "protective", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "Antibodies specifically bind RhaPS backbone.", "mechanism": "RhaPS-OMV immunisation induces IgG antibodies that opsonise and promote phagocytosis of Strep A.", "protein": "Rhamnose Polysaccharide (RhaPS)", "relationship_type": "protective", "source_pmcid": "PMC7618470" }, { "confidence": "medium", "disease": "Necrotising fasciitis", "glycan_involvement": "GAC glycan structure is conserved.", "mechanism": "GAC is present in all invasive Strep A strains causing necrotising fasciitis.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "biomarker", "source_pmcid": "PMC7618470" }, { "confidence": "medium", "disease": "Streptococcal toxic shock syndrome", "glycan_involvement": "GAC glycan structure is conserved.", "mechanism": "GAC is a universal marker for Strep A strains causing toxic shock.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "biomarker", "source_pmcid": "PMC7618470" }, { "confidence": "medium", "disease": "Streptococcus pyogenes infection", "glycan_involvement": "RhaPS backbone stimulates immune response.", "mechanism": "RhaPS-OMV vaccine candidate triggers IL-17A production, suggesting cellular immunity against Strep A.", "protein": "Rhamnose Polysaccharide (RhaPS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Streptococcus dysgalactiae subsp. equisimilis infection", "glycan_involvement": "GAC glycan structure present in SDSE_gac.", "mechanism": "SDSE_gac isolates express GAC, enabling detection and targeting by anti-GAC antibodies.", "protein": "Group A Carbohydrate (GAC)", "relationship_type": "biomarker", "source_pmcid": "PMC7618470" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "Glycosylation affects AST stability and serum half-life.", "mechanism": "Elevated AST levels indicate hepatocellular injury during remdesivir treatment.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC7644402" }, { "confidence": "high", "disease": "Drug-induced liver injury", "glycan_involvement": "Glycosylation affects ALT secretion and stability.", "mechanism": "Elevated ALT levels indicate hepatocellular injury during remdesivir treatment.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7644402" }, { "confidence": "medium", "disease": "Coronavirus Disease 2019 (COVID-19)", "glycan_involvement": "Glycosylation may modulate AST serum levels.", "mechanism": "AST elevation is observed in COVID-19 patients, reflecting liver involvement.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC7644402" }, { "confidence": "medium", "disease": "Coronavirus Disease 2019 (COVID-19)", "glycan_involvement": "Glycosylation may modulate ALT serum levels.", "mechanism": "ALT elevation is observed in COVID-19 patients, reflecting liver involvement.", "protein": "Alanine Aminotransferase (ALT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7644402" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialylated glycans (\u03b12,3 or \u03b12,6 linked) on host glycoproteins are essential for HA binding and host specificity.", "mechanism": "HA binds sialic acid-containing glycoproteins on host respiratory epithelial cells to mediate viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein and ACE2 modulates binding affinity and immune evasion.", "mechanism": "S protein binds ACE2 glycoprotein receptor on host cells to mediate SARS-CoV-2 entry.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Sialylated glycans and DPP4 glycosylation are critical for viral attachment and entry.", "mechanism": "MERS-CoV S protein binds \u03b12,3-linked sialic acids and DPP4 glycoprotein receptor for cell entry.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is heavily glycosylated, which shields it from immune recognition and is essential for receptor binding.", "mechanism": "gp120 binds to CD4 and co-receptors on host cells, facilitating HIV-1 entry.", "protein": "gp120", "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Recognizes high-mannose glycans on viral glycoproteins.", "mechanism": "DC-SIGN acts as a secondary receptor for influenza A virus entry after initial sialic acid binding.", "protein": "DC-SIGN (CD209)", "protein_enriched": { "function": "Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which ar", "gene_name": "CD209", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G35541EV", "G62765YT", "G79666IR", "G93718GY" ], "uniprot_id": "Q9NNX6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Binds high-mannose glycans on viral glycoproteins.", "mechanism": "L-SIGN facilitates influenza A virus entry as a secondary receptor.", "protein": "L-SIGN (CD209L)", "protein_enriched": { "function": "Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Is a rec", "gene_name": "CLEC4M", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "Q9H2X3" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Japanese Encephalitis", "glycan_involvement": "Sialylation pattern determines host susceptibility.", "mechanism": "Viral attachment to host sialylated glycoproteins is a key step in infection.", "protein": "Sialic acid-binding glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Sialyllactose moiety mimics natural sialylated glycoproteins.", "mechanism": "Multivalent sialyllactose conjugates can capture and inactivate influenza virus by mimicking host glycoprotein receptors.", "protein": "Sialyllactose-conjugated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Glycosylation is essential for infectivity and immune evasion.", "mechanism": "Envelope glycoproteins mediate viral entry via interaction with host cell surface glycans.", "protein": "Glycosylated viral envelope proteins", "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "medium", "disease": "Herpes Simplex Virus Infection", "glycan_involvement": "Glycosylation modulates host cell binding and immune evasion.", "mechanism": "Envelope glycoproteins interact with host cell surface glycans for viral entry.", "protein": "Glycosylated viral envelope proteins", "relationship_type": "causal", "source_pmcid": "PMC7647396" }, { "confidence": "high", "disease": "COVID-19 (severe/life-threatening)", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2; LA binding alters conformation and infectivity.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7654389" }, { "confidence": "high", "disease": "COVID-19 (severe/life-threatening)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Type I IFNs provide innate antiviral defense; deficiency or neutralization increases disease severity.", "protein": "Interferon-\u03b1 (IFN-\u03b1)", "relationship_type": "protective", "source_pmcid": "PMC7654389" }, { "confidence": "high", "disease": "COVID-19 (severe/life-threatening)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Type I IFNs provide innate antiviral defense; deficiency or neutralization increases disease severity.", "protein": "Interferon-\u03b2 (IFN-\u03b2)", "relationship_type": "protective", "source_pmcid": "PMC7654389" }, { "confidence": "high", "disease": "COVID-19 (severe/life-threatening)", "glycan_involvement": "N-glycosylation required for secretion and stability.", "mechanism": "Type I IFNs provide innate antiviral defense; neutralizing autoantibodies impair response.", "protein": "Interferon-\u03c9 (IFN-\u03c9)", "protein_enriched": { "function": "", "gene_name": "IFNW1", "glycan_count": 4, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G31685JQ", "G32072NY", "G74724QE", "G82348BZ" ], "uniprot_id": "P05000" }, "relationship_type": "protective", "source_pmcid": "PMC7654389" }, { "confidence": "high", "disease": "COVID-19 (severe/life-threatening)", "glycan_involvement": "Fc N-glycosylation modulates effector function and autoantibody activity.", "mechanism": "Autoantibodies (IgG) neutralize type I IFNs, impairing antiviral immunity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7654389" }, { "confidence": "medium", "disease": "Antiphospholipid syndrome (secondary to COVID-19)", "glycan_involvement": "N-glycosylation affects prothrombin folding and function.", "mechanism": "Autoantibodies against prothrombin (aPS/PT) associated with thrombosis and severe COVID-19.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7654389" }, { "confidence": "high", "disease": "Chronic hepatitis C", "glycan_involvement": "Heavily glycosylated; glycosylation required for stability and function.", "mechanism": "sCD163 is released upon macrophage activation and correlates with fibrosis and NASH severity.", "protein": "CD163 (sCD163)", "relationship_type": "biomarker", "source_pmcid": "PMC7672678" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation affects secretion and immune recognition.", "mechanism": "SerpinB3 activates monocytes, increases sCD163 and pro-inflammatory cytokines, promoting fibrogenesis.", "protein": "SerpinB3 (SCCA1)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7672678" }, { "confidence": "medium", "disease": "NASH (nonalcoholic steatohepatitis)", "glycan_involvement": "IgM is highly glycosylated; glycan moieties may affect complex formation.", "mechanism": "Circulating SCCA-IgM complex is a marker of disease progression and NASH in chronic hepatitis C.", "protein": "SCCA-IgM complex", "relationship_type": "biomarker", "source_pmcid": "PMC7672678" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "N-glycosylation modulates cell adhesion and signaling.", "mechanism": "EpCAM is upregulated in HCC cancer stem cells, associated with drug resistance.", "protein": "EpCAM", "protein_enriched": { "function": "May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as", "gene_name": "EPCAM", "glycan_count": 65, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G02815KT", "G05724UK", "G06110VR", "G27915IV", "G28541PG", "G28681TP", "G31852PQ", "G39188ZX", "G39446WN", "G41247ZX", "G57776ZU", "G62765YT", "G64527OM", "G92050GC", "G57321FI", "G00273SJ", "G00912UN", "G04657PL", "G08918WF", "G14972EH", "G20706XG", "G27058EU", "G43223CG", "G45395BF", "G48414YA", "G57776ZS", "G59324HL", "G68490OW", "G80075MS", "G83229XP", "G83646BJ", "G87661QW", "G92062TF", "G98611JV", "G06356OH", "G10773YW", "G11629QQ", "G11870QZ", "G20312EM", "G23294PN", "G24084IV", "G25418HZ", "G25451PN", "G34617SM", "G34989PA", "G37399XV", "G44215PV", "G47012YE", "G47518TP", "G59536GA", "G60177UT", "G64394MX", "G66760KM", "G70375MX", "G75983OB", "G80223IX", "G81263BG", "G82463GQ", "G82830MN", "G84452RH", "G90382BL", "G92135MA", "G95133RI", "G96577RX", "G49108TO" ], "uniprot_id": "P16422" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7672678" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "Heavily glycosylated; glycosylation modulates ligand binding.", "mechanism": "CD44 is a marker of cancer stem cells; expression correlates with stemness and resistance.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7672678" }, { "confidence": "high", "disease": "Hepatocellular carcinoma (HCC)", "glycan_involvement": "EGF-like repeats are O-fucosylated, essential for ligand interaction.", "mechanism": "Notch1 activation promotes CSC phenotype and drug resistance; ZBP-89 represses Notch1.", "protein": "Notch1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7672678" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation stabilizes tight junctions.", "mechanism": "Increased Occludin expression strengthens intestinal barrier, reducing liver injury.", "protein": "Occludin", "protein_enriched": { "function": "May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions", "gene_name": "OCLN", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR" ], "uniprot_id": "Q16625" }, "relationship_type": "protective", "source_pmcid": "PMC7672678" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "Glycosylation may affect protein-protein interactions.", "mechanism": "Upregulation improves barrier function, limiting endotoxin translocation.", "protein": "Tjp-1 (ZO-1)", "relationship_type": "protective", "source_pmcid": "PMC7672678" }, { "confidence": "medium", "disease": "Immune-mediated hepatitis", "glycan_involvement": "N-glycosylation required for surface expression.", "mechanism": "Fas upregulation promotes hepatocyte apoptosis in immune-mediated liver injury.", "protein": "Fas (CD95)", "relationship_type": "causal", "source_pmcid": "PMC7672678" }, { "confidence": "medium", "disease": "Immune-mediated hepatitis", "glycan_involvement": "N-glycosylation modulates receptor function.", "mechanism": "DR5 mediates apoptosis; downregulation by Akkermansia muciniphila is protective.", "protein": "DR5 (TNFRSF10B)", "relationship_type": "causal", "source_pmcid": "PMC7672678" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells, enabling infection.", "protein": "Spike glycoprotein (S protein) of SARS-CoV-2", "relationship_type": "causal", "source_pmcid": "PMC7677609" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor, initiating infection.", "protein": "Spike glycoprotein (S protein) of SARS-CoV", "relationship_type": "causal", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 may influence spike binding affinity.", "mechanism": "Acts as the host receptor for SARS-CoV-2 spike protein, facilitating viral entry.", "protein": "ACE2 (Angiotensin-converting enzyme 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycosylation status may modulate interaction with viral spike.", "mechanism": "Serves as the entry receptor for SARS-CoV spike protein.", "protein": "ACE2 (Angiotensin-converting enzyme 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "Inflammatory lung disease", "glycan_involvement": "Glycosylation may affect immune recognition and pathogenesis.", "mechanism": "Spike-ACE2 interaction alters ACE2 function, contributing to inflammation and vascular permeability.", "protein": "Spike glycoprotein (S protein) of SARS-CoV-2", "relationship_type": "causal", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "Inflammatory lung disease", "glycan_involvement": "Glycosylation modulates immune evasion and receptor interaction.", "mechanism": "Spike-ACE2 binding disrupts ACE2 function, promoting inflammation.", "protein": "Spike glycoprotein (S protein) of SARS-CoV", "relationship_type": "causal", "source_pmcid": "PMC7677609" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts antigenicity and vaccine design.", "mechanism": "Target for antiviral drugs and vaccines due to its essential role in viral entry.", "protein": "Spike glycoprotein (S protein) of SARS-CoV-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7677609" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects immune response and drug accessibility.", "mechanism": "Target for antiviral strategies due to its role in host cell entry.", "protein": "Spike glycoprotein (S protein) of SARS-CoV", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Presence indicates active infection; used in diagnostics.", "protein": "Spike glycoprotein (S protein) of SARS-CoV-2", "relationship_type": "biomarker", "source_pmcid": "PMC7677609" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycosylation may influence assay performance.", "mechanism": "Presence indicates SARS-CoV infection.", "protein": "Spike glycoprotein (S protein) of SARS-CoV", "relationship_type": "biomarker", "source_pmcid": "PMC7677609" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7682129" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects spike binding affinity.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via interaction with spike protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7682129" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation influences host tropism and immune recognition.", "mechanism": "Facilitates viral entry into host cells via ACE2 binding.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7682129" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "Neutralizing antibodies in convalescent plasma bind spike protein, blocking infection.", "protein": "Immunoglobulin G1 (IgG1)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHG1", "glycan_count": 221, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G00420UH", "G00432WW", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03382KH", "G03574QJ", "G05642HQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09197ZW", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G11254FL", "G11453BM", "G11745XZ", "G11870QZ", "G12398HZ", "G12580WI", "G14260UH", "G14994KB", "G15038BD", "G15486FH", "G15828HX", "G17336WC", "G19379ID", "G20218ZS", "G20449BJ", "G22140GZ", "G22340YC", "G22674CI", "G22768VO", "G23295TF", "G23432EQ", "G23453IV", "G23719VF", "G23770JR", "G23863VK", "G25079LO", "G25520XG", "G25987BV", "G27919IH", "G28541PG", "G28603RA", "G28663KH", "G28681TP", "G29651HS", "G29880MM", "G30159WR", "G31616YD", "G31852PQ", "G31916IQ", "G31936TA", "G32814EW", "G33244HE", "G33271XM", "G34730YF", "G35029YA", "G36191CD", "G37868ZX", "G39213VZ", "G39446WN", "G39943KJ", "G40834TG", "G41247ZX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G45889JQ", "G46687AB", "G46902YN", "G48390IG", "G48414YA", "G48584BU", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50842MS", "G51287LK", "G52162PS", "G52589SM", "G54600FO", "G55052CN", "G56903ZB", "G57317CE", "G57776ZU", "G57818FI", "G58667NI", "G59451NL", "G59471TH", "G59626AS", "G59937CP", "G60145BJ", "G60923RB", "G61334IA", "G61627IG", "G61855PQ", "G61937QU", "G62765YT", "G62894KT", "G64481DJ", "G64527OM", "G65092SV", "G65184UU", "G66760KM", "G66933CM", "G66937TJ", "G67324HN", "G67381VP", "G68318VE", "G68698AP", "G70101JE", "G71013KY", "G71812IK", "G72291OX", "G72787SB", "G72790NZ", "G72791KH", "G74430RZ", "G75798PH", "G77653XA", "G78059CC", "G79568CQ", "G80475RE", "G80858MF", "G80920RR", "G81295CK", "G82081LV", "G83161QT", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84618NL", "G85740DB", "G85767HW", "G86500WE", "G87051GH", "G88374WZ", "G88421PE", "G88725PI", "G89993FE", "G90659AW", "G90725ZC", "G90734RJ", "G91636VS", "G92050GC", "G92129PT", "G92597CK", "G94854LT", "G95865ZB", "G98719SR", "G99858XP", "G02030ZB", "G03127AL", "G05850WN", "G07483YN", "G08146BT", "G10773YW", "G11041DA", "G11535IB", "G11629QQ", "G12708JQ", "G14127XU", "G14669DU", "G15169WU", "G16828VN", "G22310AV", "G23294PN", "G24835MQ", "G26403SG", "G32611KT", "G33609NS", "G33780DA", "G36836GD", "G39188ZX", "G40702WU", "G42358LZ", "G43157UW", "G43694RQ", "G47518TP", "G49108TO", "G50636SI", "G52934AK", "G55220VL", "G56749GV", "G60230HH", "G62831KM", "G65219TP", "G66538GV", "G69411IG", "G70418MS", "G72667IM", "G72718TT", "G72735IY", "G72956NR", "G74724QE", "G75983OB", "G80966KZ", "G81263BG", "G81282CC", "G81413UE", "G82119TF", "G82463GQ", "G83355KE", "G84467IZ", "G84820NF", "G89319AW", "G91023GB", "G91365ZQ", "G91473PK", "G92570PJ", "G94239KE" ], "uniprot_id": "P01857" }, "relationship_type": "protective", "source_pmcid": "PMC7682129" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fusion protein glycosylation enhances stability and binding.", "mechanism": "Recombinant fusion protein neutralizes spike protein, preventing viral entry.", "protein": "Fc-fused ACE2 (ACE2-Ig)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7682129" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation involvement mentioned.", "mechanism": "Essential for viral polyprotein cleavage and replication; target for inhibitors.", "protein": "Protease (Mpro/3CLpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7682129" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation involvement mentioned.", "mechanism": "Cleaves viral polyproteins; inhibition blocks replication.", "protein": "PL-pro (Papain-like protease)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7682129" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Polysaccharide structure modulates immune activation.", "mechanism": "Microbial \u03b2-glucans enhance host immune response against coronavirus.", "protein": "\u03b2-glucans", "relationship_type": "protective", "source_pmcid": "PMC7682129" }, { "confidence": "high", "disease": "Respiratory tract infection", "glycan_involvement": "Glycosylation shields epitopes from immune detection.", "mechanism": "Spike-mediated entry leads to infection of respiratory epithelial cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7682129" }, { "confidence": "medium", "disease": "Myocardial tissue damage", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Viral entry via spike-ACE2 interaction damages cardiac tissues.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7682129" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition", "mechanism": "Mediates viral entry by binding to ACE2 on host cells", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects spike binding affinity", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via spike protein binding", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7691822" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function", "mechanism": "Seroconversion indicates immune response and potential protection", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC7691822" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects stability and function", "mechanism": "Early seroconversion marker for acute infection", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7691822" }, { "confidence": "medium", "disease": "Cytokine storm syndrome", "glycan_involvement": "Glycan shield may modulate immune activation", "mechanism": "Triggers immune activation leading to hyperinflammation", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "Cytokine storm syndrome", "glycan_involvement": "Glycosylation required for secretion and activity", "mechanism": "Elevated in severe COVID-19, drives hyperinflammatory response", "protein": "Interleukin 6 (IL-6)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation modulates tropism and immune evasion", "mechanism": "Viral entry into lung epithelial cells causes pneumonia", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Glycan shield may affect tissue tropism", "mechanism": "Infection of ACE2-expressing vascular cells leads to vascular inflammation", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion", "mechanism": "Mediates viral entry via ACE2, similar to SARS-CoV-2", "protein": "SARS-CoV-1 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion", "mechanism": "Mediates viral entry via DPP4 receptor", "protein": "MERS-CoV Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7691822" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of Spike is critical for receptor binding and immune evasion.", "mechanism": "Spike glycoprotein binds to ACE2, mediating viral entry into host cells.", "protein": "Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7714043" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Targeted by vaccines and monoclonal antibodies to block viral entry.", "protein": "Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7714043" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence ACE2-Spike interaction.", "mechanism": "Soluble recombinant ACE2 blocks Spike binding, preventing viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7714043" }, { "confidence": "medium", "disease": "Acute respiratory distress", "glycan_involvement": "Glycosylation may affect ACE2 stability and function.", "mechanism": "Spike-ACE2 complex endocytosis reduces ACE2, increasing Ang II and inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7714043" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "Antibodies against Spike glycoprotein neutralize virus and prevent infection.", "protein": "Antibody (IgG)", "relationship_type": "protective", "source_pmcid": "PMC7714043" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns affect detection and immune response.", "mechanism": "Spike is used as a diagnostic marker and vaccine antigen.", "protein": "Spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7714043" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may regulate ACE2 cell surface expression.", "mechanism": "ACE2 expression correlates with tissue susceptibility to infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7714043" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect drug binding sites.", "mechanism": "Drug screening targets Spike-ACE2 interaction to block viral entry.", "protein": "Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7714043" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts antibody stability and half-life.", "mechanism": "Monoclonal antibodies against Spike used for passive immunization.", "protein": "Antibody (IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7714043" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation influences immunogenicity and vaccine efficacy.", "mechanism": "mRNA vaccines encode Spike glycoprotein to elicit immune response.", "protein": "Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7714043" }, { "confidence": "medium", "disease": "Eastern Equine Encephalitis (EEE)", "glycan_involvement": "IgG glycosylation affects Fc receptor binding and anti-inflammatory activity, relevant for IVIG efficacy.", "mechanism": "IVIG (intravenous immunoglobulin, primarily IgG) administration may modulate immune response and improve outcomes in EEE patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic", "source_pmcid": "PMC7777322" }, { "confidence": "medium", "disease": "Eastern Equine Encephalitis (EEE)", "glycan_involvement": "IgM is heavily glycosylated, which influences its stability and immune recognition.", "mechanism": "IgM antibodies are used for serological diagnosis of EEE infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7777322" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "Glycosylation affects IgG effector function and detection sensitivity.", "mechanism": "IgG antibodies are detected in response to SARS-CoV-2 infection; used in serological tests.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "Glycosylation influences IgM structure and immune recognition.", "mechanism": "IgM antibodies indicate recent infection; used in rapid diagnostic tests.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding and infectivity.", "mechanism": "ACE2 is the functional receptor for SARS-CoV-2 entry into host cells.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation may affect its stability and function.", "mechanism": "Elevated CRP levels correlate with severe Covid-19 and systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "medium", "disease": "Covid-19", "glycan_involvement": "Glycosylation modulates solubility and immune interactions.", "mechanism": "Increased in severe Covid-19 as part of the acute phase response.", "protein": "Serum amyloid A protein", "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "medium", "disease": "Covid-19", "glycan_involvement": "Ferritin is glycosylated, which may influence its serum levels.", "mechanism": "Elevated ferritin is associated with severe Covid-19 and hyperinflammation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "Glycosylation affects IL-6 secretion and receptor binding.", "mechanism": "IL-6 is elevated in severe Covid-19 and cytokine storm; target for immunomodulatory therapy.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Covid-19", "glycan_involvement": "D-dimer is a glycosylated fibrin fragment; glycosylation may affect clearance.", "mechanism": "Elevated D-dimer indicates coagulopathy and predicts severe Covid-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "medium", "disease": "Covid-19", "glycan_involvement": "N-glycosylation is essential for fibrinogen secretion and function.", "mechanism": "Increased fibrinogen is linked to hypercoagulability in severe Covid-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "Glycosylation of ACE2 may modulate cardiovascular effects.", "mechanism": "ACE2 is implicated in heart function; SARS-CoV-2 infection may worsen heart failure.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC7790363" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "Glycosylation provides bacterial binding sites.", "mechanism": "Pellicle glycoproteins mediate bacterial adhesion, initiating plaque formation and caries.", "protein": "Acquired enamel pellicle", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "O-glycans mediate bacterial binding and aggregation.", "mechanism": "Mucins inhibit bacterial adhesion and buffer acids.", "protein": "Salivary mucins", "relationship_type": "protective", "source_pmcid": "PMC7811793" }, { "confidence": "high", "disease": "Dental caries", "glycan_involvement": "Recognition of host glycan motifs.", "mechanism": "Bacterial adhesins bind to glycoproteins in the pellicle, promoting colonization.", "protein": "Streptococcal adhesins", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation modulates cell adhesion.", "mechanism": "Altered glycoprotein expression affects epithelial attachment, facilitating bacterial invasion.", "protein": "Junctional epithelium glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Periodontal disease", "glycan_involvement": "Glycosylation affects matrix stability.", "mechanism": "Matrix glycoprotein degradation leads to ligament breakdown.", "protein": "Periodontal ligament glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Enamel hypoplasia", "glycan_involvement": "N- and O-glycosylation critical for protein function.", "mechanism": "Defective glycoprotein secretion impairs enamel formation.", "protein": "Ameloblasts (enamel matrix proteins)", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Odontogenic keratocyst", "glycan_involvement": "Glycosylation affects epithelial barrier properties.", "mechanism": "Keratinized glycoprotein lining supports cyst persistence and recurrence.", "protein": "Keratinized epithelium (odontogenic cyst lining)", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Dentigerous cyst", "glycan_involvement": "Glycosylation modulates cell proliferation.", "mechanism": "Proliferation of glycoprotein-rich epithelial rests forms cysts.", "protein": "Epithelial rests of Malassez", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "low", "disease": "Osteopetrosis-associated dental defects", "glycan_involvement": "Glycosylation required for matrix assembly.", "mechanism": "Altered glycoprotein secretion affects dentin and tooth development.", "protein": "Odontoblasts (dentin matrix proteins)", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "medium", "disease": "Dental calculus (tartar)", "glycan_involvement": "O-glycans bind calcium and phosphate.", "mechanism": "Mucin glycoproteins nucleate mineral deposition in plaque.", "protein": "Salivary mucins", "relationship_type": "causal", "source_pmcid": "PMC7811793" }, { "confidence": "high", "disease": "Intrauterine Growth Restriction (IUGR)", "glycan_involvement": "Leptin is a glycoprotein; glycosylation affects its secretion and stability.", "mechanism": "Lower umbilical cord blood leptin in IUGR neonates reflects reduced fetal adipose tissue and impaired growth.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "biomarker", "source_pmcid": "PMC7817282" }, { "confidence": "medium", "disease": "Intrauterine Growth Restriction (IUGR)", "glycan_involvement": "Therapeutic leptin requires proper glycosylation for function.", "mechanism": "Potential for recombinant leptin therapy to treat IUGR fetuses.", "protein": "Leptin", "protein_enriched": { "function": "Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in ", "gene_name": "LEP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41159" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7817282" }, { "confidence": "medium", "disease": "Patent Ductus Arteriosus (PDA)", "glycan_involvement": "IgM glycosylation modulates immune response and placental transfer.", "mechanism": "Presence of maternal anti-rubella IgM increases risk of PDA in congenital rubella.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7817282" }, { "confidence": "high", "disease": "Maturity-Onset Diabetes of the Young (MODY)", "glycan_involvement": "GCK is glycosylated, which may affect stability and localization.", "mechanism": "GCK mutations cause GCK-MODY, affecting glucose sensing.", "protein": "Glucokinase (GCK)", "protein_enriched": { "function": "Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (Pub", "gene_name": "GCK", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35557" }, "relationship_type": "causal", "source_pmcid": "PMC7817282" }, { "confidence": "high", "disease": "Maturity-Onset Diabetes of the Young (MODY)", "glycan_involvement": "HNF1A glycosylation may influence DNA binding and transcriptional activity.", "mechanism": "HNF1A mutations cause HNF1A-MODY, impairing insulin gene regulation.", "protein": "Hepatocyte nuclear factor 1-alpha (HNF1A)", "protein_enriched": { "function": "Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). 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"PMC7825804" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and antibody accessibility.", "mechanism": "Targeted by vaccines and neutralizing antibodies to block viral entry.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Detected in diagnostic biosensors for rapid COVID-19 testing.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Used as a target in diagnostic assays (e.g., RT-PCR, antigen tests).", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7829094" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion assembly.", "mechanism": "Structural component essential for viral assembly and morphogenesis.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7829094" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate function.", "mechanism": "Involved in virus assembly, release, and pathogenesis.", "protein": "Envelope (E) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated; glycans modulate S protein binding.", "mechanism": "Host receptor for S protein; blocking interaction prevents infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation shields and modulates receptor interaction.", "mechanism": "Mediates viral entry via ACE2 binding.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7829094" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates immune evasion.", "mechanism": "Mediates viral entry (via DPP4 receptor in MERS).", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts antigenicity and vaccine efficacy.", "mechanism": "Used as antigen in protein subunit and mRNA vaccines to elicit immunity.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC7829094" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Highly glycosylated; glycosylation affects immune evasion and receptor binding", "mechanism": "Mediates attachment and entry into host cells, determines host and tissue tropism", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Highly glycosylated; S1 variation enables immune escape", "mechanism": "Attachment to host cells and fusion, determines pathogenicity and host range", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "high", "disease": "Infectious bronchitis (IBV)", "glycan_involvement": "Highly glycosylated; S1 is major immune target, variation affects vaccine efficacy", "mechanism": "Determines tissue tropism (respiratory, kidney, gonads) and induces protective immunity", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "Transmissible gastroenteritis (TGEV)", "glycan_involvement": "Glycosylation modulates receptor binding and immune recognition", "mechanism": "Attachment and entry into enteric epithelial cells, determines host specificity", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "Murine hepatitis (MHV)", "glycan_involvement": "Glycosylation affects host range and tissue specificity", "mechanism": "Determines CNS tropism and demyelination via cell attachment", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "All coronavirus diseases (e.g., COVID-19, IBV, TGEV)", "glycan_involvement": "N- or O-glycosylation at N-terminus; type does not affect virus growth but may influence assembly", "mechanism": "Essential for virion assembly and morphogenesis", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "low", "disease": "Betacoronavirus-associated diseases (e.g., some respiratory infections)", "glycan_involvement": "Glycoprotein nature may influence receptor binding", "mechanism": "May affect tissue tropism and host adaptation", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "modulator", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "Diarrhea (human coronavirus)", "glycan_involvement": "Glycosylation may affect enteric tropism", "mechanism": "Mediates infection of enteric epithelial cells", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "Kidney disease (IBV)", "glycan_involvement": "Glycosylation may modulate tissue targeting", "mechanism": "Tissue tropism determined by S protein sequence", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "medium", "disease": "Gonadal disease (IBV)", "glycan_involvement": "Glycosylation may influence tissue tropism", "mechanism": "Enables infection of reproductive tissues", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7831903" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Dense N-glycan shield modulates immune evasion and stabilizes the open conformation for ACE2 binding.", "mechanism": "Mediates viral entry via ACE2 binding and membrane fusion.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Sparse glycosylation at RBD exposes therapeutic epitopes.", "mechanism": "Glycan shield vulnerabilities can be exploited for antibody and drug targeting.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7834635" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 N-glycans (N90, N322, N546) interact with S protein glycans, modulating binding affinity.", "mechanism": "Host receptor for SARS-CoV-2 S protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Oligomannose-type glycan (Man9) at N234 fills RBD cleft and stabilizes active conformation.", "mechanism": "Glycan at N234 stabilizes the open RBD conformation, promoting ACE2 binding.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "N-glycan shield modulates antigenicity, immune evasion, and receptor specificity.", "mechanism": "Mediates viral entry via sialic acid binding and membrane fusion.", "protein": "Influenza A Hemagglutinin (HA)", "relationship_type": "causal", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "Influenza A", "glycan_involvement": "Gain/loss of N-glycosylation sites alters antigenic properties and receptor binding.", "mechanism": "Glycan shield rearrangement affects antibody accessibility and antiviral strategies.", "protein": "Influenza A Hemagglutinin (HA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense oligomannose N-glycan shield enables immune evasion and modulates receptor/co-receptor binding.", "mechanism": "Mediates viral entry via CD4 and co-receptor binding and membrane fusion.", "protein": "HIV-1 Envelope (Env) fusion trimer", "relationship_type": "causal", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycan-glycan networks pre-structure epitopes for antibody recognition.", "mechanism": "Glycan shield structure determines accessibility for broadly neutralizing antibodies.", "protein": "HIV-1 Envelope (Env) fusion trimer", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7834635" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Variation in N-glycosylation sites and glycan types modulates antigenicity.", "mechanism": "Hypervariable glycosylation patterns correlate with viral tropism and immune escape.", "protein": "HIV-1 Envelope (Env) fusion trimer", "relationship_type": "biomarker", "source_pmcid": "PMC7834635" }, { "confidence": "medium", "disease": "Influenza A", "glycan_involvement": "Increased N-glycosylation reduces receptor binding and viral replication fitness.", "mechanism": "Number and type of N-glycosylation sites correlate with antigenic drift and viral fitness.", "protein": "Influenza A Hemagglutinin (HA)", "relationship_type": "biomarker", "source_pmcid": "PMC7834635" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7836883" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects inhibitor binding and immune recognition.", "mechanism": "Targeted by entry/fusion inhibitors (e.g., Arbidol, lipopeptides) to block virus-cell fusion.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7836883" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates S protein binding; chloroquine impairs ACE2 glycosylation.", "mechanism": "Acts as the host receptor for S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation not explicitly detailed, but E is a glycoprotein.", "mechanism": "Essential for virus assembly, budding, and pathogenesis; forms ion channels.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status not detailed, but M is a glycoprotein.", "mechanism": "Key for virion assembly and S protein incorporation into viral envelope.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation may modulate immune evasion and tissue tropism.", "mechanism": "Facilitates viral spread to lungs, leading to inflammation and ARDS.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "NRP1 is a glycoprotein; glycosylation may affect S1 binding.", "mechanism": "Binds Furin-cleaved S1 fragment, enhancing viral entry and infectivity.", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "Multiple Organ Failure", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Enables viral dissemination to multiple organs via ACE2-expressing tissues.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7836883" }, { "confidence": "medium", "disease": "Multiple Organ Failure", "glycan_involvement": "Glycosylation status may affect tissue-specific S protein binding.", "mechanism": "Widespread ACE2 expression allows multi-organ viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7836883" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns are important for antigenicity.", "mechanism": "Surface-exposed glycoprotein used for diagnostic and vaccine targeting.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7836883" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor and facilitating membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Contains N-glycosylation; important for virion formation.", "mechanism": "Essential for virus assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Minor glycosylation; role in envelope formation.", "mechanism": "Involved in virus assembly, budding, and pathogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7844806" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor interaction.", "mechanism": "Mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "N-glycosylation affects receptor binding and immune recognition.", "mechanism": "Mediates viral entry via DPP4 receptor.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binds high-mannose glycans on viral glycoproteins.", "mechanism": "MBL recognizes viral glycans and activates complement, contributing to innate immunity.", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "protective", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated, which may influence S protein binding.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 S protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (host factor)", "source_pmcid": "PMC7844806" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "N protein mutations associated with strain differences and possibly disease severity.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC7844806" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Target for neutralizing antibodies and vaccines.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7844806" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "MBL binding depends on viral glycan patterns.", "mechanism": "Genetic polymorphisms in MBL influence individual susceptibility to infection.", "protein": "Mannose-binding lectin (MBL)", "protein_enriched": { "function": "Calcium-dependent lectin involved in innate immune defense (PubMed:35102342). Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Bin", "gene_name": "MBL2", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11226" }, "relationship_type": "biomarker", "source_pmcid": "PMC7844806" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Mediates viral entry into host cells via receptor binding and membrane fusion.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7849527" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity of epitopes.", "mechanism": "Target for neutralizing antibodies and vaccine development.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence assay sensitivity/specificity.", "mechanism": "Used in diagnostics to detect infection via antibody/antigen tests.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC7849527" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shielding can modulate epitope exposure.", "mechanism": "Induces B and T cell epitopes that elicit protective immune responses.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HLA-B7 is itself glycosylated, which is essential for peptide presentation.", "mechanism": "Presents spike glycoprotein-derived epitopes to T cells, enabling cytotoxic response.", "protein": "HLA-B7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation required for proper folding and function.", "mechanism": "Plays a major role in presenting viral peptides for immune recognition.", "protein": "HLA-B7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "HIV", "glycan_involvement": "Glycosylation affects peptide binding and immune recognition.", "mechanism": "Involved in immune response to HIV peptides.", "protein": "HLA-B7", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Similar glycosylation patterns modulate immune evasion.", "mechanism": "Homologous spike glycoprotein mediates viral entry in SARS-CoV.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "homologous_causal", "source_pmcid": "PMC7849527" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation patterns affect host interaction and immune response.", "mechanism": "Homologous spike glycoprotein mediates viral entry in MERS-CoV.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "homologous_causal", "source_pmcid": "PMC7849527" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence epitope accessibility and vaccine efficacy.", "mechanism": "Multi-epitope peptides derived from spike glycoprotein can serve as vaccine candidates.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "vaccine_antigen", "source_pmcid": "PMC7849527" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates receptor binding, immune evasion, and antigenicity.", "mechanism": "Mediates viral entry via ACE2 receptor binding and membrane fusion.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation affects receptor interaction and immune recognition.", "mechanism": "Facilitates viral entry via ACE2 receptor binding and fusion.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation influences receptor binding and immune escape.", "mechanism": "Mediates viral entry via DPP4 receptor binding and fusion.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Targeted by vaccines and monoclonal antibodies to block viral entry.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7872504" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ectodomain may affect assembly and immune recognition.", "mechanism": "Essential for virion assembly and shape; interacts with S and N proteins.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Minor glycosylation may modulate function.", "mechanism": "Involved in virion assembly, budding, and immunopathology.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "ARDS", "glycan_involvement": "Glycosylation shields epitopes, modulating immune activation.", "mechanism": "Triggers strong immune response and cytokine storm leading to ARDS.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation influences tissue tropism and immune evasion.", "mechanism": "Enables infection of lower respiratory tract cells.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects assay sensitivity and specificity.", "mechanism": "S protein is detected in serological assays for diagnosis.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7872504" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "N-glycosylation of ectodomain may affect assembly and immune recognition.", "mechanism": "Drives virion assembly and interacts with S and N proteins.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7872504" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via binding to ACE2; highly glycosylated structure aids immune evasion.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC7876557" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 may affect S protein binding affinity.", "mechanism": "Acts as the main receptor for SARS-CoV-2 S glycoprotein, enabling viral entry.", "protein": "Human ACE2", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7876557" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Furin cleavage site is adjacent to glycosylated regions, influencing processing.", "mechanism": "Cleaves S glycoprotein at furin site, priming it for ACE2 binding and membrane fusion.", "protein": "Furin", "relationship_type": "causal", "source_pmcid": "PMC7876557" }, { "confidence": "medium", "disease": "Thromboinflammation", "glycan_involvement": "Glycosylation affects fibrinogen function and clot formation.", "mechanism": "Elevated by IL-6 in severe COVID-19, contributing to hypercoagulability and thrombosis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7876557" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Glycosylation required for stability and function.", "mechanism": "Acute phase glycoprotein elevated in severe inflammation and predicts disease severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC7876557" }, { "confidence": "medium", "disease": "Diarrhea in COVID-19", "glycan_involvement": "Glycosylation modulates stability and immune recognition.", "mechanism": "Elevated in intestinal inflammation associated with COVID-19-related diarrhea.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7876557" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc N-glycosylation modulates antibody-dependent cellular cytotoxicity.", "mechanism": "Neutralizing antibodies produced in response to infection; glycosylation affects effector function.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC7876557" }, { "confidence": "high", "disease": "Thromboinflammation", "glycan_involvement": "Glycosylation required for secretion and receptor binding.", "mechanism": "Drives acute phase response, increases fibrinogen, and correlates with severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC7876557" }, { "confidence": "medium", "disease": "Dysbiosis-associated inflammation", "glycan_involvement": "Glycosylation affects LPS binding and immune activation.", "mechanism": "Binds LPS from gut bacteria, promoting systemic inflammation in metabolic diseases and possibly COVID-19.", "protein": "Lipopolysaccharide-binding protein (LBP)", "protein_enriched": { "function": "Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:2412035", "gene_name": "LBP", "glycan_count": 7, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G15169WU", "G22310AV", "G47518TP", "G48414YA", "G52527GH", "G84452RH", "G94470IW" ], "uniprot_id": "P18428" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7876557" }, { "confidence": "low", "disease": "Dysbiosis-associated inflammation", "glycan_involvement": "S protein glycan-binding properties may mediate interaction with bacterial glycans.", "mechanism": "May bind rhamnosylated glycan epitopes on gut bacteria, potentially altering microbiome composition.", "protein": "SARS-CoV-2 Spike (S) glycoprotein", "relationship_type": "causal (hypothetical)", "source_pmcid": "PMC7876557" }, { "confidence": "high", "disease": "Infectious Enteritis", "glycan_involvement": "Glycosylation forms the polysaccharide-rich matrix essential for barrier function.", "mechanism": "Glycocalyx houses digestive/absorptive enzymes and forms a barrier to pathogens.", "protein": "Glycocalyx", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "high", "disease": "Infectious Enteritis", "glycan_involvement": "O-glycosylation critical for mucin gel formation and pathogen binding.", "mechanism": "Mucins trap bacteria, facilitating their removal in feces and reducing pathogen adherence.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "medium", "disease": "Colostrum Deprivation", "glycan_involvement": "Glycosylation required for binding and transport of immunoglobulins.", "mechanism": "Acts as receptor for IgA/IgM, enabling passive immunity transfer in neonates.", "protein": "Secretory Component", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "high", "disease": "Infectious Enteritis", "glycan_involvement": "N-glycosylation stabilizes IgA and mediates mucosal transport.", "mechanism": "Neutralizes pathogens at mucosal surfaces.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "medium", "disease": "Gingival Infections", "glycan_involvement": "Glycosylation enhances enzyme stability in secretions.", "mechanism": "Lyses bacterial cell walls in saliva, reducing oral bacterial load.", "protein": "Lysozyme", "protein_enriched": { "function": "Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activ", "gene_name": "LYZ", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00698" }, "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "medium", "disease": "Malabsorption", "glycan_involvement": "N-glycosylation required for stability and function.", "mechanism": "Iron-binding glycoprotein; altered levels reflect impaired absorption.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC7895291" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease", "glycan_involvement": "N-glycosylation required for proper folding and surface expression.", "mechanism": "MHC II on enterocytes presents antigens, modulating immune response; downregulation linked to disease.", "protein": "Major Histocompatibility Complex II (MHC II)", "relationship_type": "causal", "source_pmcid": "PMC7895291" }, { "confidence": "low", "disease": "Infectious Enteritis", "glycan_involvement": "Glycosylation affects enzyme activity and secretion.", "mechanism": "Shed in microvilli vesicles, may neutralize bacterial toxins.", "protein": "Alkaline Phosphatase", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "low", "disease": "Mucosal Barrier Dysfunction", "glycan_involvement": "Glycosylation may affect stability and signaling.", "mechanism": "Feedback inhibition of enterocyte mitosis, maintaining epithelial integrity.", "protein": "Chalones", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "O-glycosylation essential for mucin function.", "mechanism": "Increased goblet cell mucin secretion protects against excessive fluid loss.", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC7895291" }, { "confidence": "high", "disease": "Pemphigus foliaceus", "glycan_involvement": "Glycosylation of Dsg may affect autoantibody binding and adhesion", "mechanism": "Autoantibodies target Dsg, disrupting keratinocyte adhesion (acantholysis)", "protein": "Desmoglein (Dsg)", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "high", "disease": "Pemphigus vulgaris", "glycan_involvement": "Glycosylation modulates antigenicity and adhesion", "mechanism": "Autoantibodies target Dsg, causing loss of cell-cell adhesion and blistering", "protein": "Desmoglein (Dsg)", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Pemphigus (general)", "glycan_involvement": "Glycosylation may influence immune recognition", "mechanism": "Autoantibodies against Dsc contribute to acantholysis", "protein": "Desmocollin (Dsc)", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "high", "disease": "Bullous pemphigoid", "glycan_involvement": "Glycosylation may affect antigenicity and immune complex formation", "mechanism": "Autoantibodies target BPAG in hemidesmosomes, causing subepidermal blistering", "protein": "BPAG (Bullous pemphigoid antigen)", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "high", "disease": "Epidermolysis bullosa acquisita", "glycan_involvement": "Glycosylation may modulate immune response", "mechanism": "Autoantibodies target type VII collagen anchoring fibrils, causing dermal-epidermal separation", "protein": "Type VII Collagen", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Linear IgA bullous dermatosis", "glycan_involvement": "Glycosylation affects antigenicity", "mechanism": "Autoantibodies target laminin in basement membrane, causing blistering", "protein": "Laminin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Epidermolysis bullosa", "glycan_involvement": "Glycosylation critical for collagen stability", "mechanism": "Genetic defects in type IV collagen weaken basement membrane, causing blistering", "protein": "Type IV Collagen", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Myxedema", "glycan_involvement": "Excess glycosaminoglycan side chains", "mechanism": "Abnormal mucin (glycoprotein) deposition in dermis causes nonpitting edema", "protein": "Mucin", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Acantholysis", "glycan_involvement": "Glycosylation required for cadherin function", "mechanism": "Loss of cadherin-mediated adhesion leads to keratinocyte dissociation", "protein": "Cadherins", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "medium", "disease": "Amyloidosis", "glycan_involvement": "Glycosylation influences amyloid formation", "mechanism": "Deposition of glycosylated immunoglobulin light chains as amyloid in skin", "protein": "AL amyloid (immunoglobulin light chain)", "relationship_type": "causal", "source_pmcid": "PMC7895312" }, { "confidence": "high", "disease": "Heart failure", "glycan_involvement": "Glycosylation affects secretion and stability.", "mechanism": "Released from atrial myocytes in response to stretch; regulates fluid balance.", "protein": "Atrial natriuretic factor (ANF)", "relationship_type": "biomarker", "source_pmcid": "PMC7895636" }, { "confidence": "high", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation modulates hormone activity.", "mechanism": "Upregulated in ventricular myocytes during hypertrophy (fetal gene program).", "protein": "Atrial natriuretic factor (ANF)", "relationship_type": "biomarker", "source_pmcid": "PMC7895636" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation required for receptor binding.", "mechanism": "Acts as a trophic stimulus for hypertrophy via receptor-mediated signaling.", "protein": "Endothelin-1", "protein_enriched": { "function": "Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and ", "gene_name": "Edn1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P22387" }, "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation regulates secretion and activity.", "mechanism": "Induces fibroblast activation and extracellular matrix deposition.", "protein": "Transforming growth factor-beta (TGF-\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "high", "disease": "Fibrosis", "glycan_involvement": "Glycosylation essential for triple helix formation and stability.", "mechanism": "Excessive collagen deposition leads to myocardial and endocardial fibrosis.", "protein": "Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "medium", "disease": "Valvular insufficiency", "glycan_involvement": "Glycosaminoglycan chains critical for biomechanical properties.", "mechanism": "Altered proteoglycan content affects valve structure and function.", "protein": "Proteoglycans", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "medium", "disease": "Dilated cardiomyopathy", "glycan_involvement": "Glycosylation modulates cell-matrix interactions.", "mechanism": "Altered extracellular matrix composition impairs myocardial structure.", "protein": "Noncollagenous glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation required for ligand binding and signaling.", "mechanism": "Stretch-sensing via adhesion complexes initiates hypertrophic signaling.", "protein": "Adhesion complexes (e.g., integrins)", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "low", "disease": "Congenital heart disease", "glycan_involvement": "Glycosylation critical for structural integrity.", "mechanism": "Defects in basement membrane glycoproteins can disrupt cardiac morphogenesis.", "protein": "Basement membrane glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "medium", "disease": "Cardiac hypertrophy", "glycan_involvement": "Glycosylation modulates receptor interaction.", "mechanism": "Acts as a trophic stimulus for myocyte growth.", "protein": "Fibroblast growth factor (FGF)", "relationship_type": "causal", "source_pmcid": "PMC7895636" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry into host cells via binding to ACE2 receptor.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "causal", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects epitope accessibility and immunogenicity.", "mechanism": "RBD region contains B- and T-cell epitopes suitable for vaccine development.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated, which may influence binding affinity.", "mechanism": "Serves as the entry receptor for SARS-CoV-2 S glycoprotein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates immune evasion and receptor binding.", "mechanism": "S protein mediates entry of SARS-CoV into host cells via ACE2.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "causal", "source_pmcid": "PMC7899787" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation affects receptor binding and immune recognition.", "mechanism": "S protein mediates entry of MERS-CoV into host cells (via DPP4, not ACE2).", "protein": "S glycoprotein (Spike protein)", "relationship_type": "causal", "source_pmcid": "PMC7899787" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HLA molecules are glycosylated, affecting peptide presentation.", "mechanism": "Presents S glycoprotein-derived CTL epitopes (e.g., CVADYSVLY, FTNVYADSF) to cytotoxic T cells, promoting immune clearance.", "protein": "HLA-A*0101", "relationship_type": "protective", "source_pmcid": "PMC7899787" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of HLA-DRB5 may influence peptide binding and presentation.", "mechanism": "Presents S glycoprotein-derived helper T-cell epitopes (e.g., YRLFRKSNL, VYAWNRKRI), aiding adaptive immunity.", "protein": "HLA-DRB5*0101", "relationship_type": "protective", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns can affect detection sensitivity.", "mechanism": "Presence of S protein or its epitopes indicates infection and is used in diagnostics.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "biomarker", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shielding can limit antibody access to epitopes.", "mechanism": "B-cell epitopes (e.g., LFRKSN, SYGFQPT) are targets for neutralizing antibodies.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7899787" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence immunogenicity of these epitopes.", "mechanism": "Overlapping B- and T-cell epitopes (e.g., YRLFRKSNL) are promising for multi-epitope vaccine design.", "protein": "S glycoprotein (Spike protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7899787" }, { "confidence": "high", "disease": "Antiphospholipid syndrome", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Antibodies against beta-2 glycoprotein 1 are diagnostic for antiphospholipid syndrome, which can cause hypercoagulability.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC7900757" }, { "confidence": "medium", "disease": "COVID-19 associated coagulopathy (CAC)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Tested to rule out antiphospholipid antibody-mediated coagulopathy in COVID-19 patients.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC7900757" }, { "confidence": "medium", "disease": "COVID-19 associated coagulopathy (CAC)", "glycan_involvement": "N-glycosylation affects fibrin clot structure and function.", "mechanism": "Elevated fibrinogen is a marker and contributor to hypercoagulability in COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC7900757" }, { "confidence": "medium", "disease": "Vasculitis", "glycan_involvement": "Fc glycosylation modulates immune complex formation and inflammation.", "mechanism": "Immune complexes (IgG-containing) deposit in vessel walls, contributing to COVID-19 vasculitis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7900757" }, { "confidence": "medium", "disease": "COVID-19 associated coagulopathy (CAC)", "glycan_involvement": "Glycosylation affects tPA stability and activity.", "mechanism": "Used to lyse thrombi in microvascular free flap thrombosis in CAC.", "protein": "Tissue plasminogen activator (tPA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7900757" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation influences fibrin polymerization.", "mechanism": "Consumption and dysregulation of fibrinogen in DIC, which can be triggered by COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC7900757" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7907736" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor conformation and virus binding.", "mechanism": "Serves as entry receptor for SARS-CoV-2; targeted by inhibitors and phytochemicals.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and localization.", "mechanism": "Facilitates priming of S glycoprotein for membrane fusion.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates antigenicity and receptor interaction.", "mechanism": "Binds ACE2 to mediate viral entry; mutations affect pathogenesis.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7907736" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; targeted by glycan-binding phytochemicals.", "mechanism": "Essential for viral polyprotein processing; inhibited by flavonoids and phenolics.", "protein": "3CLpro (Main protease)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; targeted by diarylheptanoids.", "mechanism": "Processes viral polyproteins; inhibition blocks replication.", "protein": "PLpro (Papain-like protease)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; inhibition affects viral replication.", "mechanism": "Catalyzes viral RNA synthesis; inhibited by phytochemicals.", "protein": "RNA-dependent RNA polymerase (RdRp)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Limited glycosylation; may affect immunogenicity.", "mechanism": "Used in diagnostic assays; elicits immune response.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7907736" }, { "confidence": "low", "disease": "Influenza", "glycan_involvement": "Glycosylation patterns influence cross-reactivity.", "mechanism": "Targeted by anti-influenza phytochemicals due to structural similarity.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7907736" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Interacts with glycoproteins on viral envelope.", "mechanism": "Inhibits viral attachment and penetration.", "protein": "Glycyrrhizin (from Glycyrrhizae radix)", "relationship_type": "protective", "source_pmcid": "PMC7907736" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7914020" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antibody accessibility and vaccine design.", "mechanism": "Target of neutralizing antibodies and vaccines.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antigenicity and test sensitivity.", "mechanism": "Detected in antigen tests for diagnosis.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates binding affinity for S protein.", "mechanism": "Host receptor for viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7914020" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function and detection.", "mechanism": "Seroconversion indicates infection and immune response.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Critical for antiviral defense; deficiency linked to severe disease.", "protein": "Type I Interferons", "relationship_type": "protective", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "Cytokine Storm Syndrome", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "Elevated levels contribute to hyperinflammation in severe COVID-19.", "protein": "TNF\u03b1", "relationship_type": "causal", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts detection and function.", "mechanism": "Early serological marker of infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7914020" }, { "confidence": "low", "disease": "Post-COVID Syndrome (Long COVID)", "glycan_involvement": "Glycosylation may affect antigen persistence and immune modulation.", "mechanism": "Persistent immune response to viral antigens may contribute to long-term symptoms.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7914020" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation critical for mucosal transport and function.", "mechanism": "Mucosal antibody response; detected in serological assays.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC7914020" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation affects receptor binding, immune evasion, and antigenicity.", "mechanism": "Mediates viral entry via ACE2 receptor binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation modulates receptor interaction and immune recognition.", "mechanism": "Mediates viral entry via DPP4 (CD26) receptor binding and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "high", "disease": "Common cold", "glycan_involvement": "Glycosylation influences host range and immune evasion.", "mechanism": "Mediates entry of HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1 into respiratory epithelium.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Gastroenteritis", "glycan_involvement": "Glycosylation affects tissue tropism.", "mechanism": "Mediates entry of animal CoVs (e.g., TGEV, PEDV, BCoV) into gastrointestinal tract cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation impacts epitope accessibility and antibody binding.", "mechanism": "Target of neutralizing antibodies and vaccine development.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Ectodomain is glycosylated; may affect virion assembly and immune recognition.", "mechanism": "Essential for virion assembly and genome packaging.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Lectin activity binds sialic acids; glycosylation modulates function.", "mechanism": "Enhances virulence and cell entry in HCoV-OC43 and HCoV-HKU1.", "protein": "Hemagglutinin-esterase glycoprotein (HE)", "relationship_type": "enhancer", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Feline Infectious Peritonitis", "glycan_involvement": "Glycosylation affects host specificity.", "mechanism": "Mediates entry of FIPV into feline cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Avian Infectious Bronchitis", "glycan_involvement": "Glycosylation modulates host range.", "mechanism": "Mediates entry of IBV into avian respiratory cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "medium", "disease": "Multiple sclerosis-like demyelinating disease", "glycan_involvement": "Glycosylation influences neuroinvasion.", "mechanism": "MHV spike mediates neurotropism and demyelination in mice.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7917440" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding", "mechanism": "Mediates viral entry by binding to host cell receptors (ACE-2, CD147)", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC7923689" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation of ACE-2 affects S protein binding affinity", "mechanism": "Acts as the main entry receptor for SARS-CoV-2 S protein", "protein": "ACE-2 (Angiotensin-converting enzyme 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N-glycosylation required for S protein interaction", "mechanism": "Proposed alternative receptor for S protein facilitating viral entry", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates function and cell surface expression", "mechanism": "Upregulates matrix metalloproteinases, promoting tumor progression", "protein": "CD147 (Basigin)", "relationship_type": "biomarker", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation affects receptor stability and function", "mechanism": "Regulates blood pressure via angiotensin metabolism; target of antihypertensive drugs", "protein": "ACE-2 (Angiotensin-converting enzyme 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation required for proper folding and membrane localization", "mechanism": "Efflux pump reduces intracellular drug concentration, affecting antiviral drug bioavailability", "protein": "Permeability glycoprotein (Pgp/CD243)", "relationship_type": "protective", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "Respiratory tract infections (RTI)", "glycan_involvement": "Glycosylation modulates immune evasion and host tropism", "mechanism": "Facilitates viral entry into respiratory epithelial cells", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation status may affect drug efficacy", "mechanism": "Antibiotics (e.g., doxycycline, azithromycin) reduce CD147 expression, potentially limiting viral entry", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation influences ACE-2 expression and function", "mechanism": "Upregulation by antihypertensive drugs may protect against lung injury", "protein": "ACE-2 (Angiotensin-converting enzyme 2)", "relationship_type": "protective", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation may affect drug binding and neutralization", "mechanism": "Targeted by repurposed drugs (e.g., virginiamycin, amphotericin B) to block viral entry", "protein": "Spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7923689" }, { "confidence": "medium", "disease": "Erythema multiforme", "glycan_involvement": "Spike protein is heavily glycosylated, influencing immune recognition", "mechanism": "Lymphocyte-mediated hypersensitivity reaction to viral antigens in skin", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7942232" }, { "confidence": "medium", "disease": "Mucocutaneous lesions", "glycan_involvement": "Glycosylation modulates antigenicity and tissue tropism", "mechanism": "Spike protein detected in skin endothelial and epithelial cells, triggering immune response", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7942232" }, { "confidence": "medium", "disease": "Oral ulceration", "glycan_involvement": "Glycosylation affects immune evasion and mucosal infection", "mechanism": "Viral antigens in oral mucosa induce local immune reaction", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC7942232" }, { "confidence": "low", "disease": "Mucocutaneous lesions", "glycan_involvement": "Host glycoproteins serve as viral receptors; glycosylation status affects susceptibility", "mechanism": "Spike protein binds to host glycoproteins, facilitating viral entry and immune activation", "protein": "Endothelial cell glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC7942232" }, { "confidence": "low", "disease": "Mucocutaneous lesions", "glycan_involvement": "Glycosylation may modulate cell-virus interactions", "mechanism": "Spike protein presence in eccrine gland cells triggers local immune response", "protein": "Epithelial cell glycoproteins (eccrine glands)", "relationship_type": "causal", "source_pmcid": "PMC7942232" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding", "mechanism": "Mediates viral entry by binding ACE2 on host cells", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects receptor conformation and virus binding", "mechanism": "Acts as the main receptor for SARS-CoV-2 entry", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "Multiple organ failure", "glycan_involvement": "Glycosylation enables immune evasion and broad tissue tropism", "mechanism": "Viral entry via ACE2 in multiple organs leads to systemic infection", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "Glycosylation required for stability and function in plasma", "mechanism": "Acts as anticoagulant; deficiency leads to increased clotting risk in COVID-19", "protein": "Protein S (PROS1)", "relationship_type": "protective/biomarker", "source_pmcid": "PMC7974322" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation required for proper folding and ligand recognition", "mechanism": "TLR activation by viral RNA and LPS triggers proinflammatory cytokine release", "protein": "Toll-like receptors (TLRs)", "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation modulates secretion and receptor interaction", "mechanism": "Overproduction drives systemic inflammation and organ damage", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "Derived from glycosylated fibrin; glycan status not directly discussed", "mechanism": "Elevated levels indicate increased fibrin degradation and clotting", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7974322" }, { "confidence": "medium", "disease": "Kidney injury", "glycan_involvement": "N-glycosylation may influence tissue distribution and viral interaction", "mechanism": "High ACE2 expression in kidney facilitates viral entry and damage", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "Glycosylation affects secretion and activity", "mechanism": "Proinflammatory cytokine contributing to lung injury", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation shields viral epitopes from immune detection", "mechanism": "Mediates infection of lung epithelial cells", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC7974322" }, { "confidence": "high", "disease": "Amyloidosis", "glycan_involvement": "N-glycosylation affects stability and aggregation propensity.", "mechanism": "Misfolded ATTR forms amyloid deposits; risk factor in COVID-19 autopsies.", "protein": "Transthyretin (ATTR)", "relationship_type": "causal", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates ATTR aggregation.", "mechanism": "ATTR amyloidosis found in COVID-19 autopsies; may worsen microcirculatory impairment.", "protein": "Transthyretin (ATTR)", "relationship_type": "risk factor", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation required for Sort1 function.", "mechanism": "Sort1 knockout alters bile acid metabolism (TCA3S elevation) relevant to COVID-19 metabolic changes.", "protein": "Sortilin 1 (Sort1)", "relationship_type": "biomarker", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects enzyme stability and serum half-life.", "mechanism": "Altered choline/benzoate metabolism in COVID-19 may reflect cholinesterase activity changes.", "protein": "Cholinesterase (Butyrylcholinesterase)", "relationship_type": "biomarker", "source_pmcid": "PMC7975132" }, { "confidence": "high", "disease": "Alzheimer disease (AD)", "glycan_involvement": "N- and O-glycosylation modulate APP processing.", "mechanism": "APP misprocessing leads to amyloid-beta plaques in AD; similar vesicular changes seen in COVID-19 autopsies.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Bile acid-binding glycoproteins are often N-glycosylated.", "mechanism": "Elevated TCA3S in severe COVID-19; reflects altered bile acid metabolism.", "protein": "Taurochenodeoxycholic acid 3-sulfate (TCA3S)-binding proteins", "relationship_type": "biomarker", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "Cholestasis", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "TUDCA-S is protective in cholestasis and neurodegeneration; elevated in COVID-19.", "protein": "Tauroursodeoxycholic acid sulfate (TUDCA-S)-binding proteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects TBG stability and hormone binding.", "mechanism": "Lower serum thyroxine in severe COVID-19; TBG is main carrier.", "protein": "Thyroxine-binding globulin", "relationship_type": "biomarker", "source_pmcid": "PMC7975132" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation modulates fibrin polymerization.", "mechanism": "Fibrinogen is central to clot formation; microthrombi found in COVID-19 autopsies.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "causal", "source_pmcid": "PMC7975132" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc N-glycosylation modulates effector function.", "mechanism": "IgG glycosylation status may influence immune response and severity.", "protein": "Immunoglobulins (IgG)", "relationship_type": "biomarker", "source_pmcid": "PMC7975132" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike glycoprotein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and assay sensitivity.", "mechanism": "Detected in antigen-based diagnostic assays.", "protein": "Spike glycoprotein (S-protein)", "relationship_type": "biomarker", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Used as a target in antigen and nucleic acid-based diagnostics.", "protein": "Nucleocapsid phosphoprotein (N-protein)", "relationship_type": "biomarker", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function and detection.", "mechanism": "Host antibody response detected in serological tests.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects stability and detection.", "mechanism": "Early host antibody response detected in serological tests.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC7988262" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation may affect assembly and immune recognition.", "mechanism": "Maintains viral membrane integrity and promotes viral entry.", "protein": "Membrane protein (M-protein)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may influence assembly.", "mechanism": "Plays a structural role in viral assembly.", "protein": "Envelope protein (E-protein)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates S-protein binding.", "mechanism": "Host receptor for S-protein, mediating viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry in SARS-CoV infection.", "protein": "Spike glycoprotein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry in MERS-CoV infection.", "protein": "Spike glycoprotein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC7988262" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates viral binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; miRNAs can downregulate ACE2 to reduce infection risk.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "TMPRSS2 glycosylation affects protease activity and S protein processing.", "mechanism": "TMPRSS2 primes SARS-CoV-2 S protein for cell entry; miRNAs can downregulate TMPRSS2 to inhibit viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is heavily glycosylated, shielding epitopes and modulating immune recognition.", "mechanism": "miRNAs target S protein mRNA to inhibit viral replication and entry.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N protein is glycosylated, influencing RNA binding and immune evasion.", "mechanism": "miRNAs target N protein mRNA to block viral assembly and replication.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "medium", "disease": "Nephropathy", "glycan_involvement": "ACE2 glycosylation may affect renal tropism of virus.", "mechanism": "miR-18 upregulates ACE2 in nephropathy, increasing susceptibility to SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC7989380" }, { "confidence": "medium", "disease": "Lung fibrosis", "glycan_involvement": "TGFBR1 glycosylation modulates receptor signaling.", "mechanism": "miR-3934-3p downregulates TGFBR1/SMAD3 pathway, reducing lung fibrosis risk in COVID-19.", "protein": "TGFBR1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "BCL2 glycosylation may affect apoptotic signaling.", "mechanism": "miR-1307-3p targets BCL2, promoting apoptosis and inhibiting viral proliferation.", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may regulate Ddx58 localization and function.", "mechanism": "miR-124-3p downregulates Ddx58, reducing SARS-CoV-2 replication.", "protein": "Ddx58 (RIG-I)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7989380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IL-10 glycosylation affects cytokine stability and activity.", "mechanism": "miR-127-3p regulates BCL6, inhibiting IL-10 expression and modulating immune response.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC7989380" }, { "confidence": "low", "disease": "Gastrointestinal infection", "glycan_involvement": "TMPRSS2 glycosylation may affect tissue-specific activity.", "mechanism": "TMPRSS2 targeted by miRNAs in gut, influencing GI infection in COVID-19.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC7989380" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is heavily N-glycosylated, which affects receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2; ivermectin binds S2 subunit, potentially causing conformational changes that disrupt spike-ACE2 interaction.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Protease itself is not glycosylated but processes glycoprotein substrates.", "mechanism": "Main protease primes spike protein for host cell entry; ivermectin binds and inhibits protease activity.", "protein": "SARS-CoV-2 Main Protease (3CLpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but acts on viral RNA for glycoprotein synthesis.", "mechanism": "Replicase is essential for viral RNA synthesis; ivermectin binds and inhibits replicase.", "protein": "SARS-CoV-2 Replicase (NSP9)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Indirect; RDRP activity is required for glycoprotein production.", "mechanism": "RDRP is required for viral genome replication; ivermectin binds active site and inhibits polymerase.", "protein": "SARS-CoV-2 RNA-dependent RNA polymerase (RDRP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which affects spike binding and viral entry.", "mechanism": "ACE2 is the host receptor for spike glycoprotein; ivermectin binds weakly, potentially modulating viral entry.", "protein": "Human ACE2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "TMPRSS2 is glycosylated, which may affect its protease activity and localization.", "mechanism": "TMPRSS2 primes spike protein for fusion; ivermectin binds and may inhibit TMPRSS2, blocking viral entry.", "protein": "Human TMPRSS2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Phosphorylation, not glycosylation, is primary modification.", "mechanism": "Ivermectin may bind nucleocapsid protein, inhibiting viral replication and assembly.", "protein": "SARS-CoV-2 Nucleocapsid Phosphoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation.", "mechanism": "Ivermectin binds nsp14, potentially inhibiting viral replication and assembly.", "protein": "SARS-CoV-2 nsp14", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Gangliosides are glycosphingolipids with sialic acid; glycan moieties mediate spike binding.", "mechanism": "Hydroxychloroquine binds sialic acid residues on gangliosides, inhibiting spike protein interaction and viral entry.", "protein": "Membrane Ganglioside (sialic acid-containing)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC7996102" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HLA proteins are highly glycosylated, affecting antigen presentation.", "mechanism": "Ivermectin alters expression of HLA class proteins, potentially modulating immune response to SARS-CoV-2.", "protein": "HLA Class Proteins", "relationship_type": "biomarker", "source_pmcid": "PMC7996102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding and membrane fusion.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and vaccine design.", "mechanism": "Target for peptide vaccines and neutralizing antibodies.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8009270" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates S protein binding.", "mechanism": "Host receptor for S protein; determines tissue tropism and disease severity.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status not detailed; functional as a glycoprotein.", "mechanism": "Involved in virus assembly, budding, and stimulates NLRP3 inflammasome (IL-1\u03b2 production).", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assembly and immune evasion.", "mechanism": "Involved in virion morphogenesis and assembly.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Not applicable.", "mechanism": "Autoantibodies against L1 EN found in SARS patients; increased L1 EN expression in lungs.", "protein": "L1 Endonuclease (EN)", "relationship_type": "biomarker", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "Autoimmune diseases (e.g., SLE, Sjogren\u2019s)", "glycan_involvement": "Not applicable.", "mechanism": "Enhanced L1 expression stimulates interferon, contributing to autoimmunity.", "protein": "L1 Endonuclease (EN)", "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "Immune system dysregulation (autoimmunity, cancer)", "glycan_involvement": "Not specified.", "mechanism": "Insertion into immune gene loci modulates immune responses.", "protein": "HERV-K (HML10)", "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "TLR2 is glycosylated; glycosylation affects ligand recognition.", "mechanism": "Induced by S protein, mediates innate immune activation.", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC8009270" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not specified.", "mechanism": "Interacts with S protein; inhibition proposed as antiviral strategy.", "protein": "Ezrin", "protein_enriched": { "function": "Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along w", "gene_name": "EZR", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P15311" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8009270" }, { "confidence": "high", "disease": "Anti-MOG antibody-associated disease", "glycan_involvement": "Glycosylation of MOG may influence antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against MOG trigger demyelination in CNS after SARS-CoV-2 infection.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8013420" }, { "confidence": "high", "disease": "Anti-NMDAR autoimmune encephalitis", "glycan_involvement": "N-glycosylation of NMDAR subunits modulates receptor function and immune recognition.", "mechanism": "Autoantibodies against NMDAR cause encephalitis post COVID-19 exposure.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8013420" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation affects MOG immunogenicity and susceptibility to autoimmunity.", "mechanism": "Immune response to MOG leads to ADEM-like changes in CNS after SARS-CoV-2 infection.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "medium", "disease": "Myelitis", "glycan_involvement": "Glycosylation may modulate MOG's immune interactions.", "mechanism": "Anti-MOG antibodies contribute to spinal cord inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "medium", "disease": "Neuritis", "glycan_involvement": "Glycosylation influences MOG's antigenic properties.", "mechanism": "Autoimmune targeting of MOG leads to nerve root inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "low", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "N-glycosylation affects NMDAR immune recognition.", "mechanism": "Autoimmune response to NMDAR may overlap with ADEM pathology.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "low", "disease": "Cerebellitis", "glycan_involvement": "Glycosylation modulates MOG's immune profile.", "mechanism": "Anti-MOG antibodies may contribute to cerebellar inflammation.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "low", "disease": "Vasculitis", "glycan_involvement": "Glycosylation may affect MOG's interaction with immune cells.", "mechanism": "Autoimmune response may extend to vascular structures in CNS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "low", "disease": "Multisystem inflammatory syndrome in children (MIS-C)", "glycan_involvement": "Glycosylation may influence NMDAR's immunogenicity.", "mechanism": "Possible involvement of NMDAR autoimmunity in MIS-C neurological symptoms.", "protein": "N-methyl-D-aspartate receptor (NMDAR)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8013420" }, { "confidence": "low", "disease": "Necrotizing myelitis", "glycan_involvement": "Glycosylation impacts MOG's immune interactions.", "mechanism": "Anti-MOG antibodies may drive severe spinal cord necrosis.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8013420" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "Glycosylation of TPO may affect antigenicity and autoantibody recognition.", "mechanism": "Elevated thyroid peroxidase antibody indicates autoimmune destruction of thyroid tissue.", "protein": "Thyroid peroxidase", "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "medium", "disease": "Primary hypothyroidism", "glycan_involvement": "Glycosylation modulates immunogenicity of thyroglobulin.", "mechanism": "Thyroglobulin antibody negativity helps differentiate subtypes of autoimmune thyroid disease.", "protein": "Thyroglobulin", "protein_enriched": { "function": "Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:17532758, PubMed:32025030). The synthesis of T3 and T4 involves iodination of sele", "gene_name": "TG", "glycan_count": 21, "glycosylation_sites_count": 21, "glytoucan_ids": [ "G00406II", "G05724UK", "G06110VR", "G10256JP", "G11870QZ", "G14669DU", "G25451PN", "G25637MV", "G39188ZX", "G49874UX", "G62894KT", "G64527OM", "G70101JE", "G72735IY", "G74430RZ", "G74724QE", "G80333GO", "G82119TF", "G94854LT", "G81315DD", "G42984ZU" ], "uniprot_id": "P01266" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "high", "disease": "Primary hypothyroidism", "glycan_involvement": "TSH glycosylation affects its stability and receptor binding.", "mechanism": "Elevated TSH is a diagnostic marker for hypothyroidism.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "medium", "disease": "Secondary adrenal insufficiency", "glycan_involvement": "Glycosylation may influence ACTH secretion and stability.", "mechanism": "Low ACTH with low cortisol indicates pituitary dysfunction.", "protein": "Adrenocorticotropic hormone (ACTH)", "protein_enriched": { "function": "Stimulates the adrenal glands to release cortisol", "gene_name": "POMC", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01189" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "medium", "disease": "Immune-related thyroiditis", "glycan_involvement": "Glycosylation can modulate TPO antigenicity.", "mechanism": "Autoantibodies against TPO mediate thyroid inflammation.", "protein": "Thyroid peroxidase", "relationship_type": "causal", "source_pmcid": "PMC8089184" }, { "confidence": "medium", "disease": "Immune-related thyroiditis", "glycan_involvement": "TSH glycosylation affects bioactivity.", "mechanism": "TSH elevation reflects thyroid dysfunction due to immune-mediated damage.", "protein": "Thyroid-stimulating hormone (TSH)", "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "low", "disease": "Hypophysitis", "glycan_involvement": "Glycosylation may affect ACTH half-life.", "mechanism": "Low ACTH is a marker of pituitary inflammation and dysfunction.", "protein": "Adrenocorticotropic hormone (ACTH)", "protein_enriched": { "function": "Stimulates the adrenal glands to release cortisol", "gene_name": "POMC", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P01189" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089184" }, { "confidence": "high", "disease": "Graves' disease", "glycan_involvement": "CD52 is a glycoprotein; glycosylation is essential for its cell surface expression and antibody recognition.", "mechanism": "Alemtuzumab targets CD52 on lymphocytes, causing lymphocyte depletion and subsequent immune dysregulation, leading to autoantibody production and Graves' disease.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC8089799" }, { "confidence": "high", "disease": "Relapsing-remitting multiple sclerosis", "glycan_involvement": "Glycosylation of CD52 is required for Alemtuzumab binding and efficacy.", "mechanism": "Alemtuzumab targets CD52 to deplete lymphocytes, reducing autoimmune attack in multiple sclerosis.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089799" }, { "confidence": "medium", "disease": "Autoimmune thyroid disease", "glycan_involvement": "Glycosylation of CD52 mediates antibody recognition.", "mechanism": "Lymphocyte depletion by Alemtuzumab (anti-CD52) can trigger immune reconstitution and autoimmunity, including thyroid disease.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "causal", "source_pmcid": "PMC8089799" }, { "confidence": "high", "disease": "Pernicious anemia", "glycan_involvement": "Intrinsic factor is a glycoprotein; glycosylation may affect antigenicity and autoantibody recognition.", "mechanism": "Autoantibodies against intrinsic factor impair vitamin B12 absorption, leading to pernicious anemia.", "protein": "Intrinsic factor", "relationship_type": "causal", "source_pmcid": "PMC8089860" }, { "confidence": "high", "disease": "Autoimmune thyroiditis", "glycan_involvement": "TPO is glycosylated; glycan structures may influence autoantibody binding.", "mechanism": "Anti-TPO antibodies indicate autoimmune destruction of thyroid tissue.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "medium", "disease": "APS-3B", "glycan_involvement": "IgG glycosylation modulates immune function and autoimmunity.", "mechanism": "Low IgG levels observed in APS-3B patient, reflecting immune dysregulation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "medium", "disease": "APS-3B", "glycan_involvement": "IgM is highly glycosylated; glycan changes can affect immune complex formation.", "mechanism": "Low IgM levels observed in APS-3B patient, reflecting immune dysregulation.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "medium", "disease": "Macrocytic anemia", "glycan_involvement": "Haptoglobin glycosylation affects its clearance and function.", "mechanism": "Low haptoglobin indicates hemolysis or ineffective erythropoiesis in macrocytic anemia.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of hem", "gene_name": "HP", "glycan_count": 299, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00273SJ", "G00912UN", "G01485JJ", "G02030ZB", "G03596YS", "G04657PL", "G04854VP", "G04909DG", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07755XJ", "G07799LX", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G10488MI", "G10846ZT", "G11629QQ", "G11911BT", "G12261QD", "G12341GU", "G14572XX", "G14669DU", "G14972EH", "G15038BD", "G15169WU", "G19379ID", "G20425TQ", "G20528HD", "G20706XG", "G22140GZ", "G22276PO", "G22310AV", "G22768VO", "G23453IV", "G23505EP", "G23863VK", "G25418HZ", "G25451PN", "G26267FS", "G26330YA", "G27058EU", "G27126ED", "G27251WT", "G27915IV", "G27947YN", "G27993JQ", "G28003YJ", "G29500SJ", "G30048DT", "G30769VJ", "G31118FR", "G31153XO", "G31916IQ", "G31986NC", "G32788FZ", "G33416PL", "G33791AF", "G36131WL", "G37412TK", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G42358LZ", "G42962KI", "G43223CG", "G43669FQ", "G44211QA", "G44215PV", "G44513XM", "G44576HQ", "G45395BF", "G45495MK", "G45504EY", "G46691LC", "G47012YE", "G47518TP", "G47737VJ", "G48414YA", "G49018RC", "G50045TK", "G50282JC", "G50856PC", "G51941GC", "G52527GH", "G54612UD", "G56307ZW", "G57776ZS", "G57818FI", "G58087IP", "G58232MG", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G60145BJ", "G60923RB", "G61256FT", "G62165AG", "G62765YT", "G63136LV", "G63381RX", "G63980BQ", "G66163OV", "G66933CM", "G69521XL", "G70087PV", "G70223PD", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72309KR", "G72747WU", "G72797UR", "G75798PH", "G75983OB", "G77338BR", "G77669RF", "G78019KD", "G78644BR", "G80075MS", "G80479JV", "G81247ZO", "G81295CK", "G82830MN", "G83009TH", "G83213GG", "G83555HU", "G84225JN", "G84452RH", "G85144OK", "G85282JO", "G85554PZ", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87051GH", "G87389XI", "G87947EJ", "G88374WZ", "G89045VA", "G90093AU", "G92551JA", "G93860XO", "G93999ON", "G94470IW", "G94917XT", "G95046LV", "G95865ZB", "G96577RX", "G98129XB", "G98425JK", "G43417UB", "G05962QB", "G06100EH", "G07810QS", "G11101UV", "G12793SR", "G19116TW", "G22208HN", "G34617SM", "G39064KU", "G46524LG", "G52114WE", "G53075ES", "G56518TU", "G64394MX", "G64751KD", "G75097UM", "G76417NN", "G77459ND", "G81263BG", "G82119TF", "G83633GK", "G83646BJ", "G85966UN", "G87015RU", "G87399DK", "G93656SY", "G98611JV", "G24835MQ", "G29880MM", "G41170ZW", "G51413EV", "G62837OZ", "G66760KM", "G74430RZ", "G74724QE", "G79568CQ", "G82348BZ", "G83229XP", "G01521EA", "G01650EU", "G02528FI", "G02628JF", "G02886BB", "G10819WX", "G11115RO", "G11314AS", "G11324RD", "G11870QZ", "G12745LE", "G13910DJ", "G14110OQ", "G14547CB", "G15664MX", "G18013WR", "G20210JR", "G20312EM", "G22572EH", "G26403SG", "G26915XM", "G28541PG", "G28622IK", "G28681TP", "G29545VG", "G30221QT", "G30248BL", "G30740WO", "G30970QQ", "G31544HA", "G31665QC", "G31852PQ", "G32926LW", "G34989PA", "G35541EV", "G36442WJ", "G37442IW", "G37818NZ", "G39595FH", "G41044JW", "G41840AI", "G41882MT", "G43005HM", "G43769HG", "G44753VC", "G46902YN", "G49589RB", "G49906RN", "G50073PQ", "G52890YB", "G54010QB", "G55132BD", "G56770VP", "G57317CE", "G57776ZU", "G57888GL", "G60834IK", "G65019XG", "G66088HZ", "G66537LK", "G68490OW", "G68735SN", "G69834CE", "G70441OD", "G73686WG", "G74381CZ", "G74728JK", "G75568BH", "G76868JS", "G78649WQ", "G78787DI", "G79286RS", "G79666IR", "G80920RR", "G81124ET", "G81637OR", "G83204BU", "G85269DF", "G86171ZO", "G86500WE", "G87123QX", "G89098OM", "G89205CJ", "G90659AW", "G91255CS", "G92081HT", "G93718GY", "G94665LC", "G95133RI", "G95678HJ", "G95977AE", "G96091TT", "G99668VU", "G99679NM", "G49108TO" ], "uniprot_id": "P00738" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "high", "disease": "APS-3B", "glycan_involvement": "Glycosylation may influence autoantigenicity.", "mechanism": "Intrinsic factor antibodies are diagnostic for APS-3B.", "protein": "Intrinsic factor", "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "high", "disease": "APS-3B", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "Anti-TPO antibodies are part of APS-3B diagnostic criteria.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8089860" }, { "confidence": "medium", "disease": "Necrotizing pancreatitis", "glycan_involvement": "Dulaglutide is a glycosylated therapeutic protein; glycosylation affects its stability and pharmacokinetics.", "mechanism": "Dulaglutide, a GLP-1 receptor agonist glycoprotein, is temporally associated with onset of necrotizing pancreatitis after dose escalation.", "protein": "Dulaglutide", "relationship_type": "causal", "source_pmcid": "PMC8089879" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation is essential for dulaglutide's function and half-life.", "mechanism": "GLP-1 agonists, including glycosylated dulaglutide, are rarely associated with acute pancreatitis.", "protein": "Dulaglutide", "relationship_type": "causal", "source_pmcid": "PMC8089879" }, { "confidence": "high", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation improves drug stability and reduces immunogenicity.", "mechanism": "Dulaglutide is used as a glycosylated GLP-1 receptor agonist to treat type 2 diabetes.", "protein": "Dulaglutide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089879" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "GLP-1 receptor is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "GLP-1 receptor is targeted by dulaglutide to enhance insulin secretion.", "protein": "GLP-1 receptor", "protein_enriched": { "function": "Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibit", "gene_name": "GRB14", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q14449" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089879" }, { "confidence": "low", "disease": "Cholecystitis", "glycan_involvement": "Indirect; glycosylation affects dulaglutide's pharmacology.", "mechanism": "Cholecystitis developed secondary to inflammatory damage after dulaglutide-associated pancreatitis.", "protein": "Dulaglutide", "relationship_type": "causal", "source_pmcid": "PMC8089879" }, { "confidence": "high", "disease": "Autoimmune Diabetes Mellitus", "glycan_involvement": "PD-1 is a glycoprotein; glycosylation modulates its stability and ligand binding.", "mechanism": "PD-1 blockade by monoclonal antibody (Pembrolizumab) disrupts immune tolerance, leading to T-cell mediated beta cell destruction.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC8089910" }, { "confidence": "high", "disease": "Autoimmune Thyroiditis", "glycan_involvement": "PD-1 glycosylation affects receptor function and immune signaling.", "mechanism": "PD-1 inhibition enhances autoreactive T cell activity, promoting thyroid autoimmunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC8089910" }, { "confidence": "medium", "disease": "Autoimmune Hepatitis", "glycan_involvement": "Glycosylation of PD-1 influences immune checkpoint signaling.", "mechanism": "PD-1 blockade leads to loss of peripheral tolerance, enabling T-cell mediated liver injury.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "causal", "source_pmcid": "PMC8089910" }, { "confidence": "high", "disease": "Non Small Cell Lung Cancer", "glycan_involvement": "Glycosylation of PD-1 may affect antibody binding and efficacy.", "mechanism": "PD-1 is targeted by monoclonal antibodies (e.g., Pembrolizumab) to restore anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089910" }, { "confidence": "high", "disease": "Non Small Cell Lung Cancer", "glycan_involvement": "PD-L1 glycosylation is critical for its stability and immune evasion.", "mechanism": "PD-L1 binds PD-1 to suppress immune response; blocking this interaction enhances anti-tumor immunity.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089910" }, { "confidence": "high", "disease": "Autoimmune Thyroiditis", "glycan_involvement": "TPO is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-TPO antibodies indicate thyroid autoimmunity.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8089910" }, { "confidence": "medium", "disease": "Autoimmune Diabetes Mellitus", "glycan_involvement": "C-peptide is a glycoprotein; glycosylation not directly discussed.", "mechanism": "Low/undetectable C-peptide reflects beta cell destruction.", "protein": "C-peptide", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8089910" }, { "confidence": "medium", "disease": "Autoimmune Diabetes Mellitus", "glycan_involvement": "Islet cell antigens are glycoproteins; glycosylation may influence autoantigenicity.", "mechanism": "Islet cell antibodies are markers of autoimmune diabetes.", "protein": "Islet cell antigen", "relationship_type": "biomarker", "source_pmcid": "PMC8089910" }, { "confidence": "medium", "disease": "Non Small Cell Lung Cancer", "glycan_involvement": "PD-L2 is glycosylated, affecting ligand-receptor interaction.", "mechanism": "PD-L2 is a ligand for PD-1; blockade disrupts immune suppression.", "protein": "PD-L2", "protein_enriched": { "function": "Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle ", "gene_name": "PDCD1LG2", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "Q9BQ51" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8089910" }, { "confidence": "medium", "disease": "Autoimmune Diabetes Mellitus", "glycan_involvement": "Glycosylation status may modulate PD-1 function and immune response.", "mechanism": "PD-1 pathway disruption is associated with immune-related adverse events including diabetes.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "biomarker", "source_pmcid": "PMC8089910" }, { "confidence": "high", "disease": "Statin-induced necrotizing autoimmune myopathy (SINAM)", "glycan_involvement": "HMGCR is a glycoprotein; glycosylation may affect antigenicity and autoantibody binding.", "mechanism": "Statins upregulate HMGCR expression in muscle, leading to autoantibody formation and immune-mediated muscle damage.", "protein": "HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase)", "relationship_type": "causal", "source_pmcid": "PMC8089996" }, { "confidence": "medium", "disease": "Statin-induced necrotizing autoimmune myopathy (SINAM)", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for its stability and function.", "mechanism": "Complement activation contributes to muscle damage; C3 deficiency reduces severity in mouse models.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC8089996" }, { "confidence": "medium", "disease": "Statin-induced necrotizing autoimmune myopathy (SINAM)", "glycan_involvement": "C5b-9 components are glycoproteins; glycosylation affects complex formation.", "mechanism": "C5b-9 deposits found in muscle biopsies indicate complement-mediated injury.", "protein": "Complement C5b-9 (Membrane Attack Complex)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8089996" }, { "confidence": "medium", "disease": "Type III hypersensitivity reaction", "glycan_involvement": "Glycosylation may modulate immune complex formation.", "mechanism": "Autoantibody-antigen complexes involving HMGCR trigger complement activation and tissue injury.", "protein": "HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase)", "relationship_type": "causal", "source_pmcid": "PMC8089996" }, { "confidence": "high", "disease": "Glycogenic hepatopathy", "glycan_involvement": "Alkaline phosphatase is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated serum levels reflect hepatocyte injury and glycogen accumulation.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "high", "disease": "Glycogenic hepatopathy", "glycan_involvement": "AST is glycosylated, which may affect its serum half-life.", "mechanism": "Elevated AST indicates hepatocellular injury due to glycogen overload.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "high", "disease": "Glycogenic hepatopathy", "glycan_involvement": "ALT is glycosylated; glycosylation may influence enzyme activity.", "mechanism": "ALT elevation parallels hepatocyte injury from glycogen accumulation.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "high", "disease": "Glycogenic hepatopathy", "glycan_involvement": "Glycogen is a glucose polymer; abnormal metabolism leads to disease.", "mechanism": "Excessive glycogen accumulation in hepatocytes causes reversible liver injury.", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC8090265" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "Glycosylation affects enzyme secretion and serum levels.", "mechanism": "Elevated levels indicate liver injury, including that from glycogen overload.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "Glycosylation may modulate enzyme stability.", "mechanism": "AST is released during hepatocyte injury.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "medium", "disease": "Acute liver injury", "glycan_involvement": "Glycosylation may modulate enzyme stability.", "mechanism": "ALT is released during hepatocyte injury.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090265" }, { "confidence": "high", "disease": "Hypercalcemia", "glycan_involvement": "PTH is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Low PTH indicates PTH-independent hypercalcemia, helping to distinguish etiology.", "protein": "Parathyroid hormone (PTH)", "relationship_type": "biomarker", "source_pmcid": "PMC8090299" }, { "confidence": "high", "disease": "Hypercalcemia", "glycan_involvement": "PTHrP is a glycoprotein; glycosylation may affect its bioactivity.", "mechanism": "Low PTHrP rules out PTHrP-mediated hypercalcemia (e.g., malignancy).", "protein": "PTH-related peptide (PTHrP)", "relationship_type": "biomarker", "source_pmcid": "PMC8090299" }, { "confidence": "medium", "disease": "Hepatic sarcoidosis", "glycan_involvement": "Alkaline phosphatase is a glycoprotein; glycosylation influences its serum levels.", "mechanism": "Elevated alkaline phosphatase indicates liver involvement in sarcoidosis.", "protein": "Alkaline phosphatase", "protein_enriched": { "function": "Alkaline phosphatase that can hydrolyze various phosphate compounds", "gene_name": "ALPP", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G83460ZZ" ], "uniprot_id": "P05187" }, "relationship_type": "biomarker", "source_pmcid": "PMC8090299" }, { "confidence": "low", "disease": "Sarcoidosis", "glycan_involvement": "Many serum proteins are glycoproteins; glycosylation affects their function.", "mechanism": "Serum protein electrophoresis used to rule out other causes (e.g., multiple myeloma).", "protein": "Serum protein (general)", "relationship_type": "biomarker", "source_pmcid": "PMC8090299" }, { "confidence": "high", "disease": "Euglycemic Diabetic Ketoacidosis (EDKA)", "glycan_involvement": "Glycosylation is essential for SGLT2 membrane localization and function.", "mechanism": "SGLT2 inhibition promotes glucosuria, leading to increased ketone body reabsorption and production, precipitating EDKA especially under stress or low insulin states.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "causal", "source_pmcid": "PMC8090351" }, { "confidence": "high", "disease": "Euglycemic Diabetic Ketoacidosis (EDKA)", "glycan_involvement": "Insulin glycosylation affects stability and secretion.", "mechanism": "Insulin suppresses ketogenesis; reduced insulin (due to dose decrease or beta cell dysfunction) increases risk of EDKA.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "protective", "source_pmcid": "PMC8090351" }, { "confidence": "medium", "disease": "Euglycemic Diabetic Ketoacidosis (EDKA)", "glycan_involvement": "Glucagon glycosylation modulates secretion and receptor interaction.", "mechanism": "Elevated glucagon-to-insulin ratio promotes ketogenesis and DKA.", "protein": "Glucagon", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "Gcg", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55095" }, "relationship_type": "causal", "source_pmcid": "PMC8090351" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation required for SGLT2 function.", "mechanism": "SGLT2 inhibitors lower blood glucose by promoting renal glucose excretion.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8090351" }, { "confidence": "medium", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects SGLT2 activity.", "mechanism": "SGLT2 inhibitor use in type 1 diabetes increases risk of EDKA due to low insulin reserve.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "causal", "source_pmcid": "PMC8090351" }, { "confidence": "high", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "Glycosylation impacts insulin pharmacokinetics.", "mechanism": "Exogenous insulin corrects hyperglycemia and prevents DKA.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8090351" }, { "confidence": "high", "disease": "Type 1 Diabetes Mellitus", "glycan_involvement": "Glycosylation affects insulin stability.", "mechanism": "Insulin replacement is essential for survival in type 1 diabetes.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8090351" }, { "confidence": "medium", "disease": "Ketosis-prone Diabetes", "glycan_involvement": "Glycosylation required for SGLT2 function.", "mechanism": "SGLT2 inhibition increases risk of ketosis and DKA in susceptible individuals.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "causal", "source_pmcid": "PMC8090351" }, { "confidence": "medium", "disease": "Ketosis-prone Diabetes", "glycan_involvement": "Glycosylation affects insulin action.", "mechanism": "Insulin therapy prevents ketosis and DKA.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "protective", "source_pmcid": "PMC8090351" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation required for SGLT2 function.", "mechanism": "SGLT2 inhibitors may promote weight loss via glucosuria.", "protein": "SGLT2 (Sodium-glucose cotransporter 2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8090351" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and affects receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates immune evasion and receptor interaction.", "mechanism": "Mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion assembly and immune recognition.", "mechanism": "Essential for virus assembly and morphogenesis.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence protein function and virulence.", "mechanism": "Involved in virus assembly, release, and pathogenesis.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binds to 9-O-acetylated neuraminic acid; glycan recognition is key.", "mechanism": "Present in some betacoronaviruses (e.g., OC43); facilitates attachment to sialic acids.", "protein": "Hemagglutinin-esterase (HE) protein", "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates spike binding affinity.", "mechanism": "Host receptor for viral entry; blocking interaction prevents infection.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8091157" }, { "confidence": "medium", "disease": "Gastrointestinal disease", "glycan_involvement": "Glycosylation of receptor affects viral binding.", "mechanism": "Receptor for group I coronaviruses (e.g., 229E).", "protein": "Aminopeptidase N", "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "medium", "disease": "Gastrointestinal disease", "glycan_involvement": "Glycosylation required for receptor function.", "mechanism": "Receptor for mouse hepatitis virus (group II coronavirus).", "protein": "Carcinoembryonic antigen family member", "relationship_type": "causal", "source_pmcid": "PMC8091157" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation state may affect viral binding.", "mechanism": "Potential receptor for OC43; may influence susceptibility.", "protein": "HLA-I molecule", "relationship_type": "biomarker", "source_pmcid": "PMC8091157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and vaccine design.", "mechanism": "Target of neutralizing antibodies and vaccines.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8091157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC8101988" }, { "confidence": "high", "disease": "COVID-19 pneumonia", "glycan_involvement": "Glycans modulate immune evasion and cell tropism.", "mechanism": "Facilitates infection of lower respiratory tract cells.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC8101988" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, affecting spike binding affinity.", "mechanism": "Host receptor for spike protein; mediates viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8101988" }, { "confidence": "medium", "disease": "Cytokine release syndrome", "glycan_involvement": "IL-6R is glycosylated, which may affect antibody binding.", "mechanism": "Targeted by monoclonal antibodies (tocilizumab, sarilumab) to reduce hyperinflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8101988" }, { "confidence": "medium", "disease": "Bacterial co-infection", "glycan_involvement": "Procalcitonin is a glycoprotein; glycosylation affects stability.", "mechanism": "Elevated in bacterial infection; used to guide antibiotic therapy in COVID-19.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC8101988" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "Convalescent plasma therapy provides passive immunity via anti-SARS-CoV-2 IgG.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective/therapeutic", "source_pmcid": "PMC8101988" }, { "confidence": "medium", "disease": "COVID-19 pneumonia", "glycan_involvement": "Glycosylation may affect secretion and activity.", "mechanism": "Released by infected cells; marker of inflammation.", "protein": "CXCL-10", "relationship_type": "biomarker", "source_pmcid": "PMC8101988" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion stability.", "mechanism": "Essential for viral assembly and pathogenesis.", "protein": "SARS-CoV-2 Envelope protein (E)", "relationship_type": "causal", "source_pmcid": "PMC8101988" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence immune recognition.", "mechanism": "Maintains viral envelope structure.", "protein": "SARS-CoV-2 Membrane protein (M)", "relationship_type": "causal", "source_pmcid": "PMC8101988" }, { "confidence": "medium", "disease": "COVID-19 pneumonia", "glycan_involvement": "Glycosylation may modulate receptor function and antibody efficacy.", "mechanism": "Blockade reduces mortality in severe cases.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8101988" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Albumin is N-glycosylated; glycosylation may affect stability and half-life.", "mechanism": "Low serum albumin is associated with severe COVID-19, reflecting systemic inflammation and increased capillary permeability.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "CRP is N-glycosylated; glycosylation modulates its function and clearance.", "mechanism": "High CRP is a marker of inflammation and predicts severe disease.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects clot formation.", "mechanism": "Elevated fibrinogen reflects hypercoagulation and inflammation in severe COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "COVID-19 (severe)", "glycan_involvement": "Globulins include immunoglobulins (heavily glycosylated); glycosylation modulates immune response.", "mechanism": "Low albumin/globulin ratio (AGR) is associated with severe disease and poor prognosis.", "protein": "Globulin", "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "COVID-19 (severe)", "glycan_involvement": "LDH is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "High LDH is a component of the CALL score and predicts severe disease.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "COVID-19 (severe)", "glycan_involvement": "Platelet surface glycoproteins mediate aggregation and immune interactions.", "mechanism": "Low platelet count is associated with increased risk of severe COVID-19.", "protein": "Platelet", "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Neutrophil surface glycoproteins regulate migration and activation.", "mechanism": "High neutrophil/albumin ratio (NAR) is an independent predictor of severe disease.", "protein": "Neutrophil", "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "N-glycosylation modulates fibrinogen function in coagulation.", "mechanism": "High fibrinogen is a marker of inflammation and risk in cardiovascular events.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "Community-acquired pneumonia", "glycan_involvement": "N-glycosylation affects albumin\u2019s serum half-life.", "mechanism": "Low albumin and high BUN/albumin ratio predict severity and mortality.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "medium", "disease": "Malignancy (general)", "glycan_involvement": "CRP glycosylation modulates immune signaling.", "mechanism": "High CRP/albumin ratio (CAR) is associated with inflammation and poor prognosis in cancer.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8114836" }, { "confidence": "high", "disease": "Pre-metastatic Niche Formation", "glycan_involvement": "Glycosylation modulates CD146 adhesive properties.", "mechanism": "CD146 on circulating tumor EVs mediates adhesion to endothelium, promoting uptake and niche formation.", "protein": "CD146", "relationship_type": "causal", "source_pmcid": "PMC8123387" }, { "confidence": "high", "disease": "Metastatic Melanoma", "glycan_involvement": "Glycosylation affects receptor stability and trafficking.", "mechanism": "Melanoma-derived EVs shuttle neurotrophin receptors to lymphatic endothelial cells, inducing lymphangiogenesis and metastasis.", "protein": "Neurotrophin receptors", "relationship_type": "causal", "source_pmcid": "PMC8123387" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for Notch ligand-receptor interaction.", "mechanism": "MM-derived EVs transfer Jagged1 to bone marrow cells, activating Notch pathway and promoting tumor progression.", "protein": "Jagged1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8123387" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation modulates ligand activity.", "mechanism": "EV-mediated transfer of Jagged2 activates Notch signaling in recipient cells, enhancing tumorigenic effects.", "protein": "Jagged2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8123387" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation essential for Notch receptor function.", "mechanism": "EVs deliver Notch2 to recipient cells, activating Notch pathway and promoting angiogenesis and drug resistance.", "protein": "Notch2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8123387" }, { "confidence": "medium", "disease": "Triple Negative Breast Cancer", "glycan_involvement": "Glycosylation influences CSF-1 receptor binding.", "mechanism": "CSF-1 on EVs promotes differentiation of pro-inflammatory macrophages, correlating with better clinical outcome.", "protein": "CSF-1", "relationship_type": "protective", "source_pmcid": "PMC8123387" }, { "confidence": "medium", "disease": "Pre-metastatic Niche Formation", "glycan_involvement": "Glycosylation regulates integrin-mediated adhesion.", "mechanism": "Integrins on EVs may contribute to endothelial uptake and metastatic niche establishment.", "protein": "Integrins", "relationship_type": "causal", "source_pmcid": "PMC8123387" }, { "confidence": "medium", "disease": "Non-Small Cell Lung Cancer", "glycan_involvement": "Glycosylation affects CD81 membrane organization.", "mechanism": "EVs enriched in CD81 tetraspanin are associated with NSCLC and may serve as diagnostic markers.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "biomarker", "source_pmcid": "PMC8123387" }, { "confidence": "medium", "disease": "Immune Activation (Cancer)", "glycan_involvement": "Glycosylation modulates antigen presentation.", "mechanism": "EVs enriched in MHC-I can trigger T-cell activation and immune responses.", "protein": "MHC-I", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8123387" }, { "confidence": "medium", "disease": "Pre-metastatic Niche Formation", "glycan_involvement": "Glycosylation regulates CD44-hyaluronan binding.", "mechanism": "CD44 on EVs may facilitate adhesion and uptake by endothelial cells, contributing to niche formation.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8123387" }, { "confidence": "high", "disease": "Fulminant purpura", "glycan_involvement": "CRP glycosylation modulates its stability and immune interactions.", "mechanism": "Elevated CRP reflects systemic inflammation and severity of vasculitis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Fulminant purpura", "glycan_involvement": "Ferritin glycosylation affects its clearance and immune recognition.", "mechanism": "High ferritin indicates hyperinflammation and macrophage activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "high", "disease": "Fulminant purpura", "glycan_involvement": "Glycosylation influences fibrinogen's clotting function.", "mechanism": "Elevated fibrinogen reflects acute phase response and coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Fulminant purpura", "glycan_involvement": "Glycosylation modulates antithrombin's inhibitory activity.", "mechanism": "Altered antithrombin III levels indicate coagulation imbalance.", "protein": "Antithrombin III", "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Fulminant purpura", "glycan_involvement": "Glycosylation is essential for protein C secretion and function.", "mechanism": "Reduced protein C activity suggests prothrombotic state.", "protein": "Protein C", "protein_enriched": { "function": "Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a p", "gene_name": "PROC", "glycan_count": 56, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G04854VP", "G06247RL", "G08146BT", "G08918WF", "G12341GU", "G17409FQ", "G32246SI", "G34306IB", "G37868ZX", "G40574BA", "G42358LZ", "G42440OJ", "G45495MK", "G48414YA", "G51941GC", "G61726TP", "G70232NH", "G79939YZ", "G94470IW", "G29931IJ", "G43417UB", "G45395BF", "G59626AS", "G62765YT", "G80920RR", "G95865ZB", "G13661YX", "G16758MX", "G30939HN", "G93860XO", "G00743WU", "G02628JF", "G08110WX", "G22310AV", "G23626NI", "G25297CU", "G37570AP", "G43346PX", "G49108TO", "G54740VA", "G54956ME", "G56284ZY", "G59655SA", "G61467QZ", "G69834CE", "G73418FX", "G76136FD", "G80735WD", "G81198YO", "G82592ZH", "G86102AA", "G94531EZ", "G95658PH", "G95977AE", "G96921ZU" ], "uniprot_id": "P04070" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Fulminant purpura", "glycan_involvement": "N-glycosylation regulates Factor VIII stability and activity.", "mechanism": "Elevated Factor VIII activity contributes to hypercoagulability.", "protein": "Coagulation Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Fulminant purpura", "glycan_involvement": "Glycosylation affects Factor IX plasma half-life.", "mechanism": "Increased Factor IX activity supports clot formation.", "protein": "Coagulation Factor IX", "protein_enriched": { "function": "Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipid", "gene_name": "F9", "glycan_count": 37, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G27608TI", "G50236GJ", "G70593HA", "G76163CP", "G96881BQ", "G10651WD", "G45637XA", "G70649KP", "G81006GJ", "G29068FM", "G43417UB", "G18717LR", "G74722FL", "G57321FI", "G10008NR", "G12743GW", "G12793SR", "G15016TE", "G15169WU", "G17827EU", "G28847IN", "G31639NG", "G32551IQ", "G38277AO", "G39595FH", "G47518TP", "G48414YA", "G52527GH", "G58489ZK", "G66088HZ", "G69834CE", "G74815GQ", "G79318PG", "G86904UH", "G87108ET", "G92975MH", "G98725UL" ], "uniprot_id": "P00740" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "IgM glycosylation modulates complement activation.", "mechanism": "IgM seroconversion indicates recent SARS-CoV-2 infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "IgG Fc glycosylation affects effector functions and inflammation.", "mechanism": "IgG seroconversion indicates later-stage or resolved infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8135528" }, { "confidence": "medium", "disease": "Multisystem inflammatory syndrome (MIS-C)", "glycan_involvement": "Spike glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Spike protein triggers immune response leading to MIS-C.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8135528" }, { "confidence": "high", "disease": "Demyelinating diseases", "glycan_involvement": "MAG is a glycoprotein; glycosylation is critical for its function in myelin-axon interaction.", "mechanism": "MAG is essential for myelin stability; its loss or dysfunction leads to demyelination.", "protein": "Myelin-associated glycoprotein (MAG)", "protein_enriched": { "function": "Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity)", "gene_name": "MAG", "glycan_count": 2, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G49108TO", "G02815KT" ], "uniprot_id": "P20916" }, "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "high", "disease": "Dysmyelinating diseases", "glycan_involvement": "PLP is glycosylated; glycosylation affects myelin compaction.", "mechanism": "PLP is a major myelin protein; mutations or abnormal glycosylation cause defective myelin.", "protein": "Proteolipid protein (PLP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "medium", "disease": "Demyelinating diseases", "glycan_involvement": "MBP is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "MBP is released during myelin breakdown; used as a marker for demyelination.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "biomarker", "source_pmcid": "PMC8142716" }, { "confidence": "high", "disease": "Polyneuropathy", "glycan_involvement": "Po is glycosylated; glycosylation is essential for adhesion and myelin integrity.", "mechanism": "Po is the major glycoprotein in peripheral myelin; defects cause peripheral neuropathy.", "protein": "Po protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "high", "disease": "Lafora disease", "glycan_involvement": "Polyglucosans are glucose polymers; abnormal glycan branching leads to storage.", "mechanism": "Abnormal accumulation of polyglucosan bodies (PAS-positive) in neurons causes epilepsy.", "protein": "Polyglucosan (Lafora body constituent)", "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "medium", "disease": "Ceroid/lipofuscinosis", "glycan_involvement": "Pigment contains glycoprotein and glycolipid components; glycosylation status affects accumulation.", "mechanism": "Storage of ceroid/lipofuscin pigment in neurons leads to neurodegeneration.", "protein": "Ceroid/lipofuscin", "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "medium", "disease": "Dysmyelinating diseases", "glycan_involvement": "Glycolipid structure is essential for myelin stability.", "mechanism": "Major glycolipid of myelin; deficiency or abnormal metabolism impairs myelin formation.", "protein": "Galactocerebroside", "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "medium", "disease": "Hypomyelinating diseases", "glycan_involvement": "N- and O-glycosylation required for oligodendrocyte function.", "mechanism": "Defective glycoprotein expression or glycosylation impairs myelination.", "protein": "Oligodendrocyte glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "medium", "disease": "Polyneuropathy", "glycan_involvement": "Glycosylation critical for Schwann cell-axon interaction.", "mechanism": "Schwann cell glycoprotein defects lead to demyelination and neuropathy.", "protein": "Schwann cell glycoproteins (general)", "relationship_type": "causal", "source_pmcid": "PMC8142716" }, { "confidence": "low", "disease": "Spongy myelinopathies", "glycan_involvement": "Glycosylation may modulate astrocyte response.", "mechanism": "Astrocyte glycoprotein expression changes in response to myelin edema.", "protein": "Astrocyte glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC8142716" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Hemagglutinin is a glycoprotein; glycosylation is essential for its function and recognition.", "mechanism": "Targeted by AgNPs and AuNPs, which inhibit its activity and block viral entry.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Neuraminidase is a glycoprotein; glycosylation affects enzymatic activity.", "mechanism": "Inhibited by AgNPs, reducing viral release from host cells.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Targeted by peptides and inhibitors to block viral entry via ACE2.", "protein": "Spike protein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "ACE2 is glycosylated; glycosylation affects spike binding affinity.", "mechanism": "Blocked by biocompatible polymers and peptides to prevent viral entry.", "protein": "ACE2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "N/A (not a glycoprotein, but viral entry involves glycoproteins).", "mechanism": "Inhibited by chitosan-curcumin nanocomposites, blocking viral replication.", "protein": "HCV nuclear protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "HIV envelope glycoproteins are highly glycosylated; protease activity is essential for processing glycoproteins.", "mechanism": "Inhibited by fullerene derivatives, blocking viral maturation.", "protein": "HIV protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Indirect; glycosylation of envelope proteins affects viral entry.", "mechanism": "Inhibited by fullerene derivatives, blocking viral replication.", "protein": "HIV reverse transcriptase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "S protein glycosylation affects protease accessibility.", "mechanism": "Protease required for S protein activation; inhibition blocks viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation near cleavage sites modulates furin processing.", "mechanism": "Cleaves S protein at polybasic site; inhibition prevents activation and entry.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8165346" }, { "confidence": "high", "disease": "Hepatitis B, Newcastle disease, HSV, HCV", "glycan_involvement": "Amino and hydroxyl groups mediate interactions with viral glycoproteins.", "mechanism": "Chitosan and derivatives inhibit viral entry and replication; used as drug delivery and antiviral agent.", "protein": "Chitosan (as a glycopolymer)", "relationship_type": "protective", "source_pmcid": "PMC8165346" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Not directly discussed; glycosylation status of AST not specified.", "mechanism": "Elevated AST at admission predicts higher risk of AKI development in COVID-19 patients.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Not directly discussed; glycosylation status of ALT not specified.", "mechanism": "Elevated ALT at admission is associated with increased AKI risk in COVID-19 patients.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not discussed.", "mechanism": "Elevated AST reflects cytolysis and correlates with disease severity in COVID-19.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not discussed.", "mechanism": "Elevated ALT is a marker of cytolysis and severe COVID-19.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "In-hospital mortality", "glycan_involvement": "Not discussed.", "mechanism": "Elevated AST at admission independently predicts higher in-hospital mortality in COVID-19.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "In-hospital mortality", "glycan_involvement": "Not discussed.", "mechanism": "Elevated ALT at admission independently predicts higher in-hospital mortality in COVID-19.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "Liver cytolysis", "glycan_involvement": "Not discussed.", "mechanism": "Elevated AST is a direct marker of cytolysis in COVID-19 patients.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "Liver cytolysis", "glycan_involvement": "Not discussed.", "mechanism": "Elevated ALT is a direct marker of cytolysis in COVID-19 patients.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "medium", "disease": "Severe lung injury", "glycan_involvement": "Not discussed.", "mechanism": "Elevated AST at admission is associated with more severe lung injury by CT scan in COVID-19.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "medium", "disease": "Severe lung injury", "glycan_involvement": "Not discussed.", "mechanism": "Elevated ALT at admission is associated with more severe lung injury by CT scan in COVID-19.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194798" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune evasion and infectivity.", "mechanism": "Spike glycoprotein mediates viral entry and immune activation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8194995" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects complement activation and clearance.", "mechanism": "Complement activation is associated with COVID-19 severity.", "protein": "Complement proteins", "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "Glycosylation modulates antigenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are linked to thrombosis risk.", "protein": "Anti-beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is glycosylated, affecting its stability and function.", "mechanism": "CRP elevation reflects systemic inflammation in COVID-19.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "high", "disease": "Deep Vein Thrombosis (DVT)", "glycan_involvement": "D-dimer fragments are derived from glycosylated fibrin.", "mechanism": "Elevated D-dimer indicates active thrombosis and fibrinolysis.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation influences tissue tropism and immune response.", "mechanism": "Spike protein may contribute to direct or indirect renal injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8194995" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation regulates complement activity.", "mechanism": "Complement activation can mediate renal inflammation and injury.", "protein": "Complement proteins", "relationship_type": "causal", "source_pmcid": "PMC8194995" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "Autoantibodies may contribute to COVID-19-associated coagulopathy.", "protein": "Anti-beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation modulates CRP function.", "mechanism": "CRP elevation is associated with AKI severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Reflects degradation of glycosylated fibrin.", "mechanism": "High D-dimer levels are linked to COVID-19 severity and thrombotic risk.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8194995" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fibrinogen glycosylation affects clot formation and inflammation.", "mechanism": "Elevated fibrinogen levels associated with increased mortality and severity in dialysis patients with COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP glycosylation modulates immune response and inflammation.", "mechanism": "Peak CRP levels correlated with risk of death and severity in COVID-19-infected dialysis patients.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Ferritin glycosylation may influence immune signaling.", "mechanism": "Severely elevated ferritin levels indicate hyperinflammation and poor prognosis.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IL-6 glycosylation affects receptor binding and signaling.", "mechanism": "Peak IL-6 levels reflect cytokine storm and disease severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Albumin glycosylation impacts vascular permeability and inflammation.", "mechanism": "Decreased albumin levels associated with poor outcomes in COVID-19-infected dialysis patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer glycan fragments reflect fibrin degradation and clotting activity.", "mechanism": "Elevated D-dimer levels linked to increased risk of death and coagulopathy.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates fibrinogen's role in pulmonary inflammation.", "mechanism": "High fibrinogen levels associated with ARDS development in COVID-19 dialysis patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "Hypoxia", "glycan_involvement": "CRP glycosylation influences inflammatory response in hypoxic conditions.", "mechanism": "Elevated CRP levels correlate with hypoxia severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "medium", "disease": "Shock", "glycan_involvement": "IL-6 glycosylation affects cytokine storm intensity.", "mechanism": "High IL-6 levels associated with shock and need for inotropes.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "AST glycosylation may affect enzyme stability and tissue injury signaling.", "mechanism": "Elevated AST levels at day 7 linked to increased mortality risk.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195164" }, { "confidence": "high", "disease": "COVID-19 pneumonia", "glycan_involvement": "Ferritin is glycosylated, which may affect its stability and serum levels.", "mechanism": "Elevated ferritin reflects hyperinflammation and cytokine storm in severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "high", "disease": "COVID-19 pneumonia", "glycan_involvement": "CRP glycosylation modulates its immune recognition and clearance.", "mechanism": "CRP is an acute-phase reactant elevated in systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "high", "disease": "COVID-19 pneumonia", "glycan_involvement": "D-dimer is a glycosylated fibrin degradation product.", "mechanism": "Elevated D-dimer indicates coagulopathy and risk of thromboembolic events.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "medium", "disease": "Septic shock", "glycan_involvement": "Glycosylation affects procalcitonin's stability and serum half-life.", "mechanism": "Procalcitonin is elevated in bacterial sepsis and can be used to distinguish bacterial from viral infection.", "protein": "Procalcitonin", "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "Albumin glycosylation can affect its half-life and renal handling.", "mechanism": "Hypoalbuminemia reflects capillary leak and renal dysfunction.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "medium", "disease": "COVID-19 pneumonia", "glycan_involvement": "LDH is glycosylated, which may influence its serum levels.", "mechanism": "Elevated LDH reflects tissue damage and cell lysis.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC8195208" }, { "confidence": "low", "disease": "Septic shock", "glycan_involvement": "p24 is glycosylated, affecting immune detection.", "mechanism": "Negative p24 antigen rules out HIV-related immunosuppression.", "protein": "HIV-1 p24 antigen", "relationship_type": "diagnostic exclusion", "source_pmcid": "PMC8195208" }, { "confidence": "low", "disease": "Community-acquired pneumonia", "glycan_involvement": "Bacterial glycoprotein antigens are detected in urine.", "mechanism": "Negative antigen test rules out pneumococcal pneumonia.", "protein": "Streptococcus pneumoniae antigen", "relationship_type": "diagnostic exclusion", "source_pmcid": "PMC8195208" }, { "confidence": "low", "disease": "Community-acquired pneumonia", "glycan_involvement": "Bacterial glycoprotein antigens are detected in urine.", "mechanism": "Negative antigen test rules out Legionella infection.", "protein": "Legionella pneumophila antigen", "relationship_type": "diagnostic exclusion", "source_pmcid": "PMC8195208" }, { "confidence": "low", "disease": "Acute hypoxic respiratory failure", "glycan_involvement": "Hemoglobin glycosylation can affect oxygen affinity.", "mechanism": "Negative HbSAG rules out sickle cell-related hypoxia.", "protein": "Hemoglobin S antigen (HbSAG)", "relationship_type": "diagnostic exclusion", "source_pmcid": "PMC8195208" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor and facilitating membrane fusion.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8205651" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation patterns influence host range and immune recognition.", "mechanism": "Mediates viral entry via ACE2 binding, similar to SARS-CoV-2.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8205651" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry via DPP4 receptor (not ACE2), but is also a glycoprotein.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8205651" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield affects antibody accessibility and vaccine efficacy.", "mechanism": "Targeted by neutralizing antibodies and entry inhibitors; key focus for drug/vaccine design.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8205651" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect detection sensitivity in assays.", "mechanism": "Presence in patient samples is diagnostic for infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8205651" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation near cleavage sites may regulate protease accessibility.", "mechanism": "Contains a unique furin cleavage site at S1/S2, enhancing cell entry and pathogenesis.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8205651" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which affects its interaction with the viral Spike protein.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2, enabling viral infection of host cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8209923" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Spike protein binds to ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8209923" }, { "confidence": "high", "disease": "Murine hepatitis virus (MHV) infection", "glycan_involvement": "CD66a is N-glycosylated, which is important for viral binding.", "mechanism": "CD66a serves as the entry receptor for MHV, analogous to ACE2 for SARS-CoV-2.", "protein": "CD66a (CEACAM1)", "relationship_type": "causal", "source_pmcid": "PMC8209923" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation modulates receptor stability and ligand binding.", "mechanism": "IL-6 receptor mediates proinflammatory signaling; its blockade or absorption can reduce cytokine storm.", "protein": "IL-6 receptor (CD126)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation affects receptor function and cytokine binding.", "mechanism": "IFN-\u03b3 receptor mediates inflammatory signaling; absorption by nanoparticles reduces inflammation.", "protein": "IFN-\u03b3 receptor (CD119)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation influences receptor conformation and signaling.", "mechanism": "TNF-\u03b1 receptor mediates inflammatory responses; its absorption by nanoparticles can mitigate cytokine storm.", "protein": "TNF-\u03b1 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "G-CSF receptor mediates granulocyte activation; absorption reduces inflammatory cell recruitment.", "protein": "G-CSF receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation modulates receptor activity.", "mechanism": "IL-1\u03b2 receptor mediates proinflammatory signaling; absorption by nanoparticles reduces inflammation.", "protein": "IL-1\u03b2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation affects receptor trafficking and ligand binding.", "mechanism": "CCR2 mediates monocyte recruitment; absorption by nanoparticles reduces leukocyte infiltration.", "protein": "MCP-1 receptor (CCR2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "CXCR3 mediates chemotaxis of immune cells; absorption by nanoparticles reduces tissue inflammation.", "protein": "IP-10 receptor (CXCR3)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8209923" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity.", "mechanism": "Acts as the host cell receptor for SARS-CoV-2 spike protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation of S protein and ACE2 modulates susceptibility.", "mechanism": "Spike-ACE2 interaction may be influenced by ACE2 upregulation in hypertensive patients.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation of S protein and furin cleavage site critical for entry.", "mechanism": "Elevated ACE2 and furin in diabetics may enhance spike-mediated viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation of furin and S protein cleavage site impacts function.", "mechanism": "Furin cleaves spike glycoprotein, facilitating viral entry; furin levels are elevated in diabetes.", "protein": "Furin", "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "medium", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation may affect ACE2 expression and spike binding.", "mechanism": "ACE2 is upregulated in COPD, increasing susceptibility to SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "medium", "disease": "Acute kidney injury (AKI)", "glycan_involvement": "Glycosylation may modulate ACE2 function in renal tissue.", "mechanism": "ACE2 expression in kidney enables direct viral infection and injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237516" }, { "confidence": "high", "disease": "Myocardial injury", "glycan_involvement": "Glycosylation affects stability and detection of troponin.", "mechanism": "Elevated hs-cTnI indicates cardiac injury in COVID-19 patients.", "protein": "High sensitivity cardiac troponin I (hs-cTnI)", "relationship_type": "biomarker", "source_pmcid": "PMC8237516" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its function.", "mechanism": "Elevated CRP is a marker of inflammation and severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8237516" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-6 glycosylation modulates secretion and activity.", "mechanism": "Elevated IL-6 is associated with cytokine storm and severity.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC8237516" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry into host cells by binding to ACE2.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237642" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and antibody accessibility.", "mechanism": "Targeted by vaccines and neutralizing antibodies to block infection.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8237642" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity/specificity.", "mechanism": "Detected in antigen-based diagnostic assays.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8237642" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence virion stability.", "mechanism": "Structural component essential for virion assembly and infectivity.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8237642" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein function.", "mechanism": "Involved in virus assembly and release.", "protein": "Envelope (E) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8237642" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; included for diagnostic relevance.", "mechanism": "Used as a target in RT-PCR diagnostic assays.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC8237642" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated; glycosylation modulates S protein binding.", "mechanism": "Acts as the host receptor for viral entry.", "protein": "Human ACE2", "relationship_type": "causal", "source_pmcid": "PMC8237642" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgM is glycosylated; glycosylation affects stability and detection.", "mechanism": "Early antibody response detected in serological assays.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8237642" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG is glycosylated; glycosylation affects effector function and detection.", "mechanism": "Later antibody response detected in serological assays.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8237642" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation may modulate immune evasion and tissue tropism.", "mechanism": "Viral entry via S protein leads to severe lung pathology in some patients.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8237642" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein is essential for proper folding, receptor binding, and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 receptor on host cells, enabling infection.", "protein": "SARS-CoV-2 Spike Protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal", "source_pmcid": "PMC8239501" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutation may alter glycan shielding and accessibility of receptor-binding domains.", "mechanism": "D614G mutation increases spike protein's open conformation, enhancing ACE2 binding and viral infectivity.", "protein": "SARS-CoV-2 Spike Protein (D614G mutant)", "relationship_type": "causal", "source_pmcid": "PMC8239501" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of Spike is essential for proper folding, receptor binding, and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry by binding ACE2 and facilitating membrane fusion.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8239685" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Palmitoylation is a lipid modification on cysteines in the cytoplasmic tail, affecting glycoprotein function.", "mechanism": "Palmitoylation of Spike is required for viral infectivity and pathogenicity; inhibition of palmitoylation reduces infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8239685" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation of RABV-G is required for proper folding, viral infectivity, and immune recognition.", "mechanism": "RABV-G mediates viral entry into host neurons and is essential for infection and neuroinvasion.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "causal", "source_pmcid": "PMC8246562" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation affects antigenicity and the ability of antibodies to recognize RABV-G.", "mechanism": "Detection of virus-neutralizing antibodies (VNA) against RABV-G in bat serum indicates recent exposure to rabies virus.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "biomarker", "source_pmcid": "PMC8246562" }, { "confidence": "high", "disease": "Rabies", "glycan_involvement": "Glycosylation state can influence vaccine efficacy and immunogenicity.", "mechanism": "RABV-G is the target of rabies vaccines and immunoglobulin therapies.", "protein": "Rabies virus glycoprotein (RABV-G)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8246562" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "CHI3L1 is a glycoprotein; glycosylation may affect its secretion and interactions.", "mechanism": "CHI3L1 is highly expressed in GBM and regulates an immunosuppressive microenvironment by reprogramming tumor-associated macrophages (TAMs) via PI3K/AKT/mTOR signaling.", "protein": "CHI3L1", "relationship_type": "causal", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may be critical for CHI3L1's binding to Gal3/Gal3BP.", "mechanism": "Targeting CHI3L1 or its complexes can attenuate immune suppression and tumor progression in GBM models.", "protein": "CHI3L1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Gal3BP is a heavily glycosylated protein; glycosylation mediates its binding properties.", "mechanism": "Gal3BP interacts with CHI3L1, competitively inhibiting CHI3L1-Gal3 signaling, reversing protumor TAM phenotype.", "protein": "Gal3BP", "relationship_type": "modulator", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Gal3 binds \u03b2-galactoside glycans; glycosylation of partners is essential for interaction.", "mechanism": "Gal3 forms a complex with CHI3L1, promoting M2-like TAM migration and immunosuppression.", "protein": "Gal3", "relationship_type": "causal/modulator", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Complex formation depends on glycan-mediated interactions.", "mechanism": "The complex activates NF\u03baB/CEBP\u03b2 transcriptional program, promoting protumor TAM phenotype and T cell exclusion.", "protein": "CHI3L1-Gal3 complex", "relationship_type": "causal", "source_pmcid": "PMC8255457" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Mimics glycan-binding motif of Gal3BP.", "mechanism": "Mimetic peptide disrupts CHI3L1-Gal3 interaction, reduces M2-like TAMs, increases M1-like TAMs and T cell infiltration.", "protein": "Gal3BP mimetic peptide", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may affect detection and stability.", "mechanism": "CHI3L1 is highly expressed in GBM tissue.", "protein": "CHI3L1", "relationship_type": "biomarker", "source_pmcid": "PMC8255457" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation mediates Gal3BP's competitive binding.", "mechanism": "Gal3BP reverses CHI3L1-Gal3 induced protumor signaling in TAMs.", "protein": "Gal3BP", "relationship_type": "protective/modulator", "source_pmcid": "PMC8255457" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation modulates stability and function in inflammation.", "mechanism": "Increased in diabetes, reflects elevated acute phase response and inflammation.", "protein": "alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation affects serum half-life and activity.", "mechanism": "Upregulated in diabetes, marker of acute phase response.", "protein": "alpha-1-antichymotrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "N-glycosylation influences iron binding and clearance.", "mechanism": "Altered abundance in diabetes, linked to iron metabolism and oxidative stress.", "protein": "serotransferrin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation modulates stability and aggregation.", "mechanism": "Altered levels post-liraglutide, associated with metabolic and cardiac risk.", "protein": "transthyretin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation critical for inhibitory function.", "mechanism": "Increased post-treatment, regulates complement and inflammation.", "protein": "plasma protease C1 inhibitor", "relationship_type": "protective", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation affects immune recognition.", "mechanism": "Increased post-treatment, involved in coagulation and vascular health.", "protein": "beta-2-glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "high", "disease": "Chronic Inflammation", "glycan_involvement": "N-glycosylation modulates hemoglobin binding.", "mechanism": "Decreased after liraglutide, marker of inflammation.", "protein": "haptoglobin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "high", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation required for complement activation.", "mechanism": "Decreased post-treatment, involved in inflammation and atherosclerosis.", "protein": "complement C3", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Type 2 Diabetes Mellitus", "glycan_involvement": "N-glycosylation affects secretion and function.", "mechanism": "Decreased after liraglutide, linked to insulin resistance.", "protein": "retinol binding protein", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "medium", "disease": "Cardiovascular Disease", "glycan_involvement": "N-glycosylation modulates copper transport and antioxidant activity.", "mechanism": "Decreased post-treatment, associated with oxidative stress and vascular risk.", "protein": "ceruloplasmin", "relationship_type": "biomarker", "source_pmcid": "PMC8265938" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive N-glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via binding to host ACE2 receptor; highly glycosylated structure facilitates immune evasion.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8290388" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates S protein interaction.", "mechanism": "Host cell receptor for SARS-CoV-2 S protein; glycosylation affects virus binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic target", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Lectins bind viral glycoproteins, blocking attachment/entry.", "mechanism": "Plant lectins inhibit coronavirus by interfering with viral replication cycle.", "protein": "Lectins", "relationship_type": "protective/therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Interact with viral glycoproteins and host cell surface glycans.", "mechanism": "Plant-derived polysaccharides inhibit viral replication and modulate immune response.", "protein": "Polysaccharides", "relationship_type": "protective/therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycoside moieties interact with spike glycoprotein.", "mechanism": "Binds avidly to surface spike protein, blocking viral entry.", "protein": "Luteolin and tetra-O-gallol-\u03b2-D glucose gall", "relationship_type": "therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylated forms may enhance binding to viral glycoproteins.", "mechanism": "Inhibits cellular entry of SARS-CoV-2 and viral replication.", "protein": "Quercetin", "relationship_type": "therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may facilitate interaction with viral glycoproteins.", "mechanism": "Displays antiviral activity against SARS-CoV-2 in silico.", "protein": "Apiin", "relationship_type": "therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycoside structure interacts with viral glycoproteins.", "mechanism": "Inhibits viral adsorption and penetration.", "protein": "Glycyrrhizin", "relationship_type": "therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation critical for function and immune evasion.", "mechanism": "Mediates viral entry via ACE2; glycosylation shields immune epitopes.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8290388" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Lectin-glycan interactions block viral attachment.", "mechanism": "Plant lectins inhibit influenza virus by binding viral glycoproteins.", "protein": "Lectins", "relationship_type": "protective/therapeutic", "source_pmcid": "PMC8290388" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 on host cells.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8291696" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which affects spike binding and viral entry.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; its expression level influences susceptibility.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8291696" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Calprotectin is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Fecal calprotectin is elevated in COVID-19 patients with intestinal inflammation.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8291696" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HD5 is O-glycosylated; glycosylation affects antimicrobial activity.", "mechanism": "HD5 antimicrobial peptide secretion is reduced after ACE2 downregulation by SARS-CoV-2, promoting dysbiosis.", "protein": "\u03b1-defensin HD5", "relationship_type": "protective", "source_pmcid": "PMC8291696" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Spike glycosylation modulates immune evasion and host interaction.", "mechanism": "Spike-ACE2 interaction may reduce ACE2 expression, leading to decreased antimicrobial peptides and gut dysbiosis, a risk factor for IBD.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal (indirect)", "source_pmcid": "PMC8291696" }, { "confidence": "medium", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "N-glycosylation of ACE2 affects its stability and function.", "mechanism": "ACE2 regulates amino acid absorption and antimicrobial peptide secretion, maintaining gut homeostasis.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC8291696" }, { "confidence": "high", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation shields spike from immune recognition, contributing to pathogenesis.", "mechanism": "Spike-mediated infection leads to cytokine storm and ARDS.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8291696" }, { "confidence": "low", "disease": "Type 2 Diabetes", "glycan_involvement": "N-glycosylation modulates ACE2 function.", "mechanism": "ACE2 dysfunction (via viral binding) may worsen metabolic regulation and inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (indirect)", "source_pmcid": "PMC8291696" }, { "confidence": "low", "disease": "Nonalcoholic Fatty Liver Disease", "glycan_involvement": "N-glycosylation affects ACE2 stability.", "mechanism": "ACE2 downregulation may impair gut-liver axis, promoting liver inflammation.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (indirect)", "source_pmcid": "PMC8291696" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "Glycosylation may affect calprotectin's detection and stability.", "mechanism": "Fecal calprotectin is a marker of intestinal inflammation in IBD.", "protein": "Calprotectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8291696" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells, initiating infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates host receptor interaction.", "mechanism": "Mediates viral entry (via DPP4, not ACE2 in MERS-CoV).", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 influences spike binding affinity.", "mechanism": "Acts as host receptor for SARS-CoV-2 spike protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "medium", "disease": "Pneumonia in pregnancy", "glycan_involvement": "Glycosylation may affect immune recognition and severity.", "mechanism": "Facilitates SARS-CoV-2 infection in pregnant women, leading to pneumonia.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation shields spike from immune detection, contributing to pathogenesis.", "mechanism": "Viral entry via spike protein can trigger severe lung injury and ARDS.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycan shield may delay immune response, contributing to dysregulation.", "mechanism": "Spike-mediated infection can trigger excessive immune response.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for proper virion assembly.", "mechanism": "Essential for viral assembly and morphogenesis.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein function and virion stability.", "mechanism": "Involved in virus assembly and release.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298322" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation status debated; may affect antigenicity.", "mechanism": "Major antigen detected in diagnostic assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC8298322" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates viral binding affinity.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8298380" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects protease activity and localization.", "mechanism": "TMPRSS2 primes the viral spike protein for cell entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC8298380" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function and half-life.", "mechanism": "Convalescent plasma and immunoglobulins provide passive immunity.", "protein": "Immunoglobulins (IgG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8298380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation regulates receptor signaling and antibody binding.", "mechanism": "IL-6R inhibitors reduce hyperinflammation in severe COVID-19.", "protein": "IL-6R", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8298380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "IFN-\u03b1 modulates antiviral immune response.", "protein": "Interferons (IFN-\u03b1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8298380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Surface glycoproteins mediate immunomodulatory effects.", "mechanism": "MSCs modulate immune response and tissue repair.", "protein": "Mesenchymal stem cell surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8298380" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for membrane localization and function.", "mechanism": "P-gp mediates drug transport and influences pharmacokinetics of COVID-19 therapies.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "biomarker", "source_pmcid": "PMC8298380" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect nuclear transport efficiency.", "mechanism": "Ivermectin inhibits importin \u03b1/\u03b21-mediated nuclear import of viral proteins.", "protein": "Importin \u03b1/\u03b21", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8298380" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Glycosylation affects clot formation and stability.", "mechanism": "Elevated fibrinogen is associated with prothrombotic state in COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8298380" }, { "confidence": "medium", "disease": "Sepsis-induced coagulopathy", "glycan_involvement": "Glycosylation modulates multimerization and platelet binding.", "mechanism": "VWF levels are altered in COVID-19-associated coagulopathy.", "protein": "Von Willebrand factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC8298380" }, { "confidence": "high", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "GPIIb-IIIa is a glycoprotein; glycosylation may affect antibody binding and immune recognition.", "mechanism": "Anti-GPIIb-IIIa antibodies detected, indicating immune-mediated platelet destruction.", "protein": "GPIIb-IIIa", "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "high", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "GPIa-IIa is a glycoprotein; glycosylation may modulate antigenicity.", "mechanism": "Anti-GPIa-IIa antibodies detected, suggesting immune targeting of platelet glycoproteins.", "protein": "GPIa-IIa", "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "vWF is heavily glycosylated; glycosylation affects its function and clearance.", "mechanism": "Elevated vWF indicates endothelial activation and prothrombotic state.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "Factor VIII is glycosylated; glycosylation is important for stability and activity.", "mechanism": "Elevated Factor VIII reflects endothelial activation and increased thrombotic risk.", "protein": "Factor VIII", "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "high", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "PF4 is glycosylated; glycosylation may influence immunogenicity.", "mechanism": "IgG antibodies to PF4-polyanion complexes detected, central to VITT pathogenesis.", "protein": "PF4 (Platelet Factor 4)", "relationship_type": "causal", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Autoimmune heparin-induced thrombocytopenia (aHIT)", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "Anti-GPIIb-IIIa antibodies are also seen in aHIT, indicating immune-mediated platelet activation.", "protein": "GPIIb-IIIa", "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "high", "disease": "Autoimmune heparin-induced thrombocytopenia (aHIT)", "glycan_involvement": "Glycosylation may modulate PF4-antibody interactions.", "mechanism": "PF4-antibody complexes drive platelet activation and thrombosis.", "protein": "PF4 (Platelet Factor 4)", "relationship_type": "causal", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Cerebral venous sinus thrombosis (CVST)", "glycan_involvement": "Glycosylation regulates vWF function in thrombosis.", "mechanism": "Elevated vWF is associated with increased risk of CVST via endothelial activation.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Portal vein thrombosis", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Anti-GPIIb-IIIa antibodies may contribute to platelet activation and thrombosis.", "protein": "GPIIb-IIIa", "relationship_type": "biomarker", "source_pmcid": "PMC8298939" }, { "confidence": "medium", "disease": "Portal vein thrombosis", "glycan_involvement": "Glycosylation may influence immunogenicity.", "mechanism": "PF4-antibody complexes implicated in thrombotic events.", "protein": "PF4 (Platelet Factor 4)", "relationship_type": "causal", "source_pmcid": "PMC8298939" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N-glycosylation critical for secretion and function.", "mechanism": "Deficiency or dysfunction of Factor VIII leads to impaired coagulation and bleeding.", "protein": "Factor VIII", "relationship_type": "causal", "source_pmcid": "PMC8320167" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "N- and O-glycosylation modulate VWF multimerization and function.", "mechanism": "VWF stabilizes Factor VIII in plasma; VWF deficiency can worsen bleeding.", "protein": "von Willebrand Factor", "relationship_type": "protective/biomarker", "source_pmcid": "PMC8320167" }, { "confidence": "high", "disease": "Acquired Hemophilia A", "glycan_involvement": "Glycosylation may affect immunogenicity.", "mechanism": "Autoantibodies neutralize Factor VIII, causing bleeding; immune suppression targets antibody production.", "protein": "Factor VIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "N-glycosylation required for secretion and activation.", "mechanism": "Prothrombin is cleaved to thrombin, driving clot formation; endothelial cells produce prothrombin.", "protein": "Prothrombin (Factor II)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Venous Thromboembolism (VTE)", "glycan_involvement": "N-glycosylation important for stability and function.", "mechanism": "Factor V is a cofactor in prothrombinase complex; endothelial cells produce FV.", "protein": "Factor V", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Bleeding Diathesis", "glycan_involvement": "Heavily glycosylated; glycosylation modulates anticoagulant activity.", "mechanism": "Thrombomodulin binds thrombin, activating protein C and downregulating coagulation.", "protein": "Thrombomodulin (CD141)", "relationship_type": "protective", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation required for surface expression.", "mechanism": "P-selectin expression on platelets is a marker of activation; studied as predictor of transfusion response.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Bleeding Diathesis", "glycan_involvement": "N-glycosylation essential for receptor function.", "mechanism": "Defective activation impairs platelet aggregation and hemostasis.", "protein": "Integrin \u03b1IIb\u03b23", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8320167" }, { "confidence": "medium", "disease": "Bleeding Diathesis", "glycan_involvement": "N-glycosylation affects surface expression and ligand binding.", "mechanism": "GPVI mediates platelet-collagen interaction; impaired signaling leads to bleeding.", "protein": "Glycoprotein VI (GPVI)", "relationship_type": "causal", "source_pmcid": "PMC8320167" }, { "confidence": "high", "disease": "Hemophilia A with inhibitors", "glycan_involvement": "Glycosylation may influence immunogenicity and inhibitor development.", "mechanism": "Development of anti-FVIII antibodies (inhibitors) blocks replacement therapy.", "protein": "Factor VIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8320167" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Beta-2 glycoprotein I is a glycoprotein; glycosylation affects its immunogenicity and antibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote thrombosis via antiphospholipid syndrome mechanisms.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate antigenicity and immune response.", "mechanism": "Presence of anti-beta-2 glycoprotein I antibodies is associated with SLE and increased thrombotic risk.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation state may influence immune recognition during infection.", "mechanism": "COVID-19 infection may trigger production of anti-beta-2 glycoprotein I antibodies, increasing VTE risk.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8330222" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Targets phospholipid-binding glycoproteins; glycosylation may affect epitope exposure.", "mechanism": "Lupus anticoagulant positivity is associated with increased risk of thrombosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Autoantibodies may recognize glycosylated epitopes.", "mechanism": "Lupus anticoagulant is commonly found in SLE patients and indicates risk for thrombosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "high", "disease": "Venous thromboembolism (VTE)", "glycan_involvement": "Cardiolipin-binding glycoproteins may be glycosylated, affecting antibody binding.", "mechanism": "Anticardiolipin antibodies promote thrombosis via antiphospholipid syndrome.", "protein": "cardiolipin antibodies", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation may modulate antigenicity.", "mechanism": "Anticardiolipin antibodies are markers for SLE and thrombotic risk.", "protein": "cardiolipin antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "low", "disease": "Multisystem Inflammatory Syndrome in Children (MIS-C)", "glycan_involvement": "Glycosylation may affect immune response post-inflammation.", "mechanism": "Anti-beta-2 glycoprotein I antibodies may be present post-MIS-C, indicating thrombotic risk.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Autoantibody targets may be glycosylated.", "mechanism": "COVID-19 may induce lupus anticoagulant, increasing VTE risk.", "protein": "lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence antibody binding.", "mechanism": "COVID-19 infection may trigger anticardiolipin antibody production.", "protein": "cardiolipin antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC8330222" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune response.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8330333" }, { "confidence": "high", "disease": "Sickle Cell Disease (SCD)", "glycan_involvement": "Glycosylation not directly involved in pathogenesis.", "mechanism": "Mutation in beta-globin leads to abnormal hemoglobin polymerization and sickling.", "protein": "Hemoglobin S (HbS)", "relationship_type": "causal", "source_pmcid": "PMC8330333" }, { "confidence": "medium", "disease": "Sickle Cell Hepatopathy", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "Elevated GGT indicates cholestasis or hepatobiliary injury.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC8330333" }, { "confidence": "medium", "disease": "Sickle Cell Hepatopathy", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates activity and serum half-life.", "mechanism": "Elevated ALP reflects biliary tract involvement.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC8330333" }, { "confidence": "medium", "disease": "Sickle Cell Disease (SCD)", "glycan_involvement": "Spike glycosylation may influence immune evasion and disease severity.", "mechanism": "COVID-19 infection exacerbates SCD complications, including hepatobiliary manifestations.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8330333" }, { "confidence": "medium", "disease": "Biliary Sludge", "glycan_involvement": "Glycosylation required for GGT function.", "mechanism": "Elevated GGT is associated with biliary tract dysfunction.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC8330333" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer is a glycosylated fibrin degradation product; glycosylation affects its clearance and detection.", "mechanism": "Elevated D-dimer indicates increased coagulation and fibrinolysis, associated with severe COVID-19 outcomes.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Ferritin is glycosylated; glycosylation may modulate immune recognition.", "mechanism": "High ferritin reflects hyperinflammation and macrophage activation in severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Troponin is glycosylated; glycosylation may affect stability and immune response.", "mechanism": "Elevated troponin indicates myocardial injury, correlating with poor COVID-19 prognosis.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "LDH is glycosylated; glycosylation may influence serum half-life.", "mechanism": "High LDH reflects tissue damage and correlates with severe COVID-19.", "protein": "LDH (Lactate Dehydrogenase)", "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CPK is glycosylated; glycosylation may affect enzyme activity.", "mechanism": "Elevated CPK indicates muscle injury, associated with severe COVID-19.", "protein": "CPK (Creatine Phosphokinase)", "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CRP is N-glycosylated; glycosylation modulates its immune functions.", "mechanism": "High CRP is a marker of systemic inflammation in severe COVID-19.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation affects D-dimer's plasma stability and detection.", "mechanism": "D-dimer is a direct marker of fibrin degradation and thrombosis risk.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "medium", "disease": "Congestive Heart Failure (CHF)", "glycan_involvement": "Glycosylation may affect troponin's immunogenicity and clearance.", "mechanism": "Elevated troponin indicates cardiac injury, a risk factor for poor outcomes in CHF and COVID-19.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8335432" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "ACE2 is N-glycosylated, which affects spike protein binding affinity.", "mechanism": "ACE2 acts as the entry receptor for SARS-CoV-2 via spike protein binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "De Quervain's thyroiditis (subacute thyroiditis)", "glycan_involvement": "Glycosylation of ACE2 modulates viral entry efficiency.", "mechanism": "High ACE2 expression in thyroid cells may facilitate direct viral infection and tissue damage.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "TMPRSS2 is glycosylated, which may affect its protease activity.", "mechanism": "TMPRSS2 cleaves spike protein, enabling viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "De Quervain's thyroiditis (subacute thyroiditis)", "glycan_involvement": "Glycosylation may modulate TMPRSS2 function.", "mechanism": "TMPRSS2 expression in thyroid facilitates SARS-CoV-2 entry and potential thyroiditis.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "De Quervain's thyroiditis (subacute thyroiditis)", "glycan_involvement": "TPO is glycosylated; glycan structures may influence antigenicity.", "mechanism": "Presence of antithyroid peroxidase antibodies indicates autoimmune thyroid involvement.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8339010" }, { "confidence": "high", "disease": "SARS-CoV-2 infection (COVID-19)", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike protein mediates viral entry via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein (S1 subunit)", "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "De Quervain's thyroiditis (subacute thyroiditis)", "glycan_involvement": "Glycosylation affects spike-ACE2 interaction and immune evasion.", "mechanism": "Spike protein-ACE2 interaction in thyroid may trigger local infection and inflammation.", "protein": "SARS-CoV-2 Spike protein (S1 subunit)", "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "TPO glycosylation may affect antibody binding.", "mechanism": "Antithyroid peroxidase antibodies are associated with thyroid dysfunction.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8339010" }, { "confidence": "medium", "disease": "Hypothyroidism", "glycan_involvement": "Glycosylation may modulate immunogenicity.", "mechanism": "Autoimmune response against TPO can lead to hypothyroid phase post-thyroiditis.", "protein": "Thyroid peroxidase (TPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8339010" }, { "confidence": "low", "disease": "Hypothyroidism", "glycan_involvement": "N-glycosylation of ACE2 influences viral entry and tissue tropism.", "mechanism": "Viral entry via ACE2 may cause thyroid cell apoptosis, leading to hypothyroidism.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8339010" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is heavily glycosylated, which modulates immune evasion and receptor binding.", "mechanism": "S protein mediates viral entry into host cells via ACE2 and TMPRSS2.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC8385917" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection of female reproductive tissues", "glycan_involvement": "Glycosylation of S protein may affect cell binding and immune recognition.", "mechanism": "S protein detected on corona radiata cells suggests potential for infection.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal (theoretical/susceptibility)", "source_pmcid": "PMC8385917" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection of female reproductive tissues", "glycan_involvement": "ACE2 is glycosylated, which can influence S protein binding.", "mechanism": "ACE2 expression in reproductive tissues may allow viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal (susceptibility factor)", "source_pmcid": "PMC8385917" }, { "confidence": "medium", "disease": "SARS-CoV-2 infection of female reproductive tissues", "glycan_involvement": "TMPRSS2 is a glycoprotein; glycosylation may affect its activity.", "mechanism": "TMPRSS2 primes S protein for membrane fusion in host cells.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal (susceptibility factor)", "source_pmcid": "PMC8385917" }, { "confidence": "high", "disease": "Transverse myelitis", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "Anti-MOG IgG antibodies are tested to rule out MOG-associated disease in transverse myelitis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8423772" }, { "confidence": "low", "disease": "Transverse myelitis", "glycan_involvement": "Spike protein is heavily glycosylated; glycan shield may influence immune response and mimicry.", "mechanism": "Molecular mimicry between spike protein and host proteins may trigger autoimmunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (hypothetical/association)", "source_pmcid": "PMC8423772" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation modulates MOG's immunogenicity.", "mechanism": "Anti-MOG antibodies are used to distinguish MS from other demyelinating diseases.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8423772" }, { "confidence": "high", "disease": "Neuromyelitis optica", "glycan_involvement": "Glycosylation affects antibody binding.", "mechanism": "Anti-MOG antibodies help differentiate NMO from other demyelinating disorders.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8423772" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for spike protein folding and immune evasion.", "mechanism": "Spike protein mediates viral entry and is the target of mRNA vaccines.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8423772" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-AQP4 autoantibodies are present in ~70% of NMOSD cases and are used for diagnosis.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may influence immune recognition.", "mechanism": "Anti-MOG autoantibodies are present in <10% of NMOSD cases, especially in AQP4-seronegative patients.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "medium", "disease": "Myelitis", "glycan_involvement": "Glycosylation of AQP4 may modulate immune response.", "mechanism": "Anti-AQP4 antibodies are associated with longitudinally extensive transverse myelitis, a core NMOSD feature.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "medium", "disease": "Myelitis", "glycan_involvement": "Glycosylation may affect MOG antigenicity.", "mechanism": "Anti-MOG antibodies can be present in myelitis, especially in NMOSD spectrum.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation may influence antibody binding.", "mechanism": "Anti-AQP4 antibodies are linked to optic neuritis in NMOSD.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Anti-MOG antibodies are associated with optic neuritis, especially in AQP4-seronegative NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8425290" }, { "confidence": "low", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Spike glycoprotein is heavily glycosylated; glycan structures may influence immunogenicity.", "mechanism": "Possible cross-reactivity or immune activation after vaccination with spike glycoprotein-expressing vector may trigger NMOSD.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal (speculative)", "source_pmcid": "PMC8425290" }, { "confidence": "high", "disease": "Multidrug resistance in cancer", "glycan_involvement": "Glycosylation required for proper folding and membrane localization.", "mechanism": "Efflux of chemotherapeutic agents from tumor cells, reducing drug efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal", "source_pmcid": "PMC8431958" }, { "confidence": "high", "disease": "Multidrug resistance in cancer", "glycan_involvement": "Glycosylation affects stability and function.", "mechanism": "Efflux of drugs from tumor cells, contributing to resistance.", "protein": "MRP protein", "relationship_type": "causal", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Used as a vector ligand for targeted drug delivery to tumors expressing \u03b1-fetoprotein receptors.", "protein": "\u03b1-fetoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation affects receptor interaction.", "mechanism": "Used as a targeting ligand for nanoparticles to tumor cells overexpressing transferrin receptors.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8431958" }, { "confidence": "low", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation may influence targeting efficiency.", "mechanism": "Used as a targeting ligand for nanoparticle delivery to tumors.", "protein": "\u03b12-glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation modulates ligand binding and receptor activation.", "mechanism": "Targeted by ligand-modified nanoparticles for selective drug delivery.", "protein": "Epidermal growth factor receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Malignant tumor", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Overexpression increases tumor vascular permeability, enhancing nanoparticle accumulation (EPR effect).", "protein": "Vascular endothelial growth factor", "relationship_type": "biomarker", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Severe immunodeficiency", "glycan_involvement": "Glycosylation affects enzyme stability and circulation time.", "mechanism": "Pegylated adenosine deaminase used as enzyme replacement therapy.", "protein": "Adenosine deaminase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Altered glycosylation patterns in cancer.", "mechanism": "Elevated in various cancers, used for diagnosis and monitoring.", "protein": "\u03b1-fetoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8431958" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Transferrin receptor overexpressed in many tumors.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC8431958" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry via binding to ACE2 receptor on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield modulates antibody accessibility.", "mechanism": "Targeted by neutralizing antibodies and vaccines to block viral entry.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "O- or N-glycosylation (group-dependent) influences virus-host interaction.", "mechanism": "Essential for viral assembly and host interaction.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycan modification mentioned.", "mechanism": "Involved in viral assembly and production of infectious virus.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycan modification mentioned.", "mechanism": "Used in diagnostic assays (e.g., gold nanoparticle-based detection).", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC8442305" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation forms smaller spikes on viral envelope.", "mechanism": "Accessory protein in some coronaviruses, contributes to viral entry and spread.", "protein": "Hemagglutinin-esterase (HE) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation may affect S protein binding.", "mechanism": "Host receptor for S protein, mediates viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates tissue tropism.", "mechanism": "Viral entry and replication in lung tissue leads to ARDS.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation impacts immune recognition.", "mechanism": "Facilitates infection of respiratory tract, leading to pneumonia.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "medium", "disease": "Multiorgan failure", "glycan_involvement": "Glycosylation may influence organ-specific infection.", "mechanism": "Broad tissue tropism via ACE2 leads to systemic infection.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8442305" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP levels at admission and during follow-up are associated with increased disease severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8468373" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation may modulate CRP's inflammatory activity.", "mechanism": "High CRP levels predict higher risk of mortality in COVID-19 patients.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8468373" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "D-dimer is a glycosylated fibrin degradation product.", "mechanism": "Elevated D-dimer at admission and during follow-up is associated with increased severity.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8468373" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation may affect D-dimer clearance and detection.", "mechanism": "High D-dimer levels predict increased mortality risk.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8468373" }, { "confidence": "high", "disease": "Bleeding (anticoagulant-related)", "glycan_involvement": "Glycosylation critical for P-gp function and drug transport.", "mechanism": "P-glycoprotein inhibition by diltiazem/verapamil increases dabigatran levels, raising bleeding risk.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "medium", "disease": "Peripheral edema", "glycan_involvement": "Glycosylation modulates P-gp trafficking and substrate specificity.", "mechanism": "PGP inhibition by bisoprolol increases dabigatran plasma levels; similar mechanisms may affect fluid balance.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "high", "disease": "Drug-induced gingival overgrowth (DIGO)", "glycan_involvement": "TGF-\u03b21 is a glycoprotein; glycosylation affects secretion and receptor binding.", "mechanism": "Amlodipine increases TGF-\u03b21 in gingival crevicular fluid, promoting extracellular matrix deposition and fibrosis.", "protein": "Transforming growth factor beta-1 (TGF-\u03b21)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8488667" }, { "confidence": "medium", "disease": "Drug-induced gingival overgrowth (DIGO)", "glycan_involvement": "PDGF-BB is glycosylated, which influences stability and activity.", "mechanism": "PDGF-BB measured but not significantly changed in DIGO; role as a marker.", "protein": "Platelet-derived growth factor-BB (PDGF-BB)", "relationship_type": "biomarker", "source_pmcid": "PMC8488667" }, { "confidence": "low", "disease": "Drug-induced gingival overgrowth (DIGO)", "glycan_involvement": "Glycosylation affects secretion and receptor interaction.", "mechanism": "bFGF not detected in sufficient samples; possible role in ECM synthesis.", "protein": "Basic fibroblast growth factor (bFGF/FGF2)", "relationship_type": "biomarker", "source_pmcid": "PMC8488667" }, { "confidence": "medium", "disease": "Drug-induced gingival overgrowth (DIGO)", "glycan_involvement": "IL-17A is glycosylated, which may affect stability and signaling.", "mechanism": "Amlodipine increases IL-17A in gingival tissue, promoting fibrosis independent of inflammation.", "protein": "Interleukin-17A (IL-17A)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8488667" }, { "confidence": "low", "disease": "Drug-induced liver injury", "glycan_involvement": "Glycosylation modulates P-gp localization in hepatocytes.", "mechanism": "Altered P-gp function may affect hepatic drug clearance, predisposing to DILI with amlodipine.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "low", "disease": "Amlodipine-induced ascites", "glycan_involvement": "Glycosylation affects P-gp function in endothelial cells.", "mechanism": "Impaired P-gp function may contribute to vascular permeability and fluid retention.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "low", "disease": "Amlodipine-induced non-cardiogenic pulmonary edema", "glycan_involvement": "Glycosylation status may influence P-gp's protective role in lung endothelium.", "mechanism": "PGP inhibition may alter vascular permeability in lungs, contributing to edema.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "medium", "disease": "Bradycardia", "glycan_involvement": "Glycosylation modulates P-gp's drug efflux capacity.", "mechanism": "Drug-drug interactions affecting P-gp can increase beta-blocker bioavailability, leading to bradycardia.", "protein": "P-glycoprotein (ABCB1)", "relationship_type": "causal", "source_pmcid": "PMC8488667" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "VWF is a heavily glycosylated plasma glycoprotein; glycosylation affects its clearance and interaction with FVIII.", "mechanism": "VWF binds FVIII, limiting its half-life; targeting VWF with BT200 prolongs FVIII half-life and increases FVIII levels.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "FVIII is glycosylated; glycosylation affects stability and plasma half-life.", "mechanism": "Deficiency or dysfunction of FVIII causes Hemophilia A.", "protein": "Factor VIII (FVIII)", "protein_enriched": { "function": "Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa", "gene_name": "F8", "glycan_count": 63, "glycosylation_sites_count": 22, "glytoucan_ids": [ "G43089EG", "G56784JY", "G00912UN", "G62765YT", "G15664MX", "G72747WU", "G22310AV", "G37881RL", "G59536GA", "G31852PQ", "G48414YA", "G80920RR", "G83460ZZ", "G29068FM", "G52527GH", "G33791AF", "G57888GL", "G22768VO", "G56014GC", "G22573RC", "G45395BF", "G93656SY", "G47518TP", "G75983OB", "G43417UB", "G10019LZ", "G00155YT", "G01543ZX", "G05724UK", "G06110VR", "G11629QQ", "G14389GM", "G15169WU", "G17689DH", "G21001NA", "G23863VK", "G26335RK", "G30460NZ", "G39188ZX", "G39595FH", "G43947VZ", "G45841FE", "G46687AB", "G48712ZJ", "G49874UX", "G51640FO", "G55521GY", "G64527OM", "G69834CE", "G70101JE", "G72291OX", "G72797UR", "G75727PF", "G78059CC", "G80858MF", "G81263BG", "G84452RH", "G86357DX", "G91413ZX", "G91636VS", "G93141AZ", "G94531EZ", "G97720QM" ], "uniprot_id": "P00451" }, "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "PF4 is a glycoprotein; glycosylation may influence immunogenicity and complex formation.", "mechanism": "PF4 forms complexes with vaccine constituents, triggering anti-PF4 antibodies that activate platelets and induce thrombosis.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "Thrombotic thrombocytopenia", "glycan_involvement": "PF4 glycosylation may affect complex formation with viral glycoproteins.", "mechanism": "PF4 complexes with SARS-CoV-2 Spike glycoprotein, inducing platelet aggregation and antibody production.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "COVID-19-associated thrombosis", "glycan_involvement": "Spike protein is highly glycosylated; glycan shield may modulate immune recognition and PF4 binding.", "mechanism": "Spike glycoprotein clusters PF4, leading to platelet activation and abnormal coagulation.", "protein": "SARS-CoV-2 Spike glycoprotein (SP)", "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "medium", "disease": "Thrombotic thrombocytopenia", "glycan_involvement": "Glycosylation of SP may affect PF4 binding and immunogenicity.", "mechanism": "SP/PF4 complexes induce platelet aggregation and antibody production, contributing to thrombocytopenia.", "protein": "SARS-CoV-2 Spike glycoprotein (SP)", "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "medium", "disease": "Hemophilia A", "glycan_involvement": "VWF glycosylation modulates its plasma levels and function.", "mechanism": "VWF levels correlate with FVIII levels and bleeding risk in Hemophilia A.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "biomarker", "source_pmcid": "PMC8495459" }, { "confidence": "medium", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "PF4 glycosylation may affect antibody recognition.", "mechanism": "Anti-PF4 antibodies are diagnostic for VITT.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "Hemophilia A", "glycan_involvement": "Glycosylation of VWF is essential for FVIII binding and protection.", "mechanism": "VWF stabilizes FVIII in circulation, protecting it from degradation.", "protein": "Von Willebrand Factor (VWF)", "relationship_type": "protective", "source_pmcid": "PMC8495459" }, { "confidence": "medium", "disease": "COVID-19-associated thrombosis", "glycan_involvement": "Glycosylation of both PF4 and Spike may modulate complex formation.", "mechanism": "PF4/Spike complexes trigger platelet activation and thrombosis.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC8495459" }, { "confidence": "high", "disease": "Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Anti-MOG IgG antibodies are associated with demyelinating attacks in the CNS.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8498413" }, { "confidence": "medium", "disease": "Acute Disseminated Encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation of MOG may modulate immune response.", "mechanism": "Anti-MOG IgG antibodies are detected in some ADEM cases, indicating immune targeting of MOG.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8498413" }, { "confidence": "low", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation may influence MOG's immunogenicity.", "mechanism": "MOG is a minor target in some MS cases, but less specific than in MOGAD.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8498413" }, { "confidence": "low", "disease": "Neuromyelitis Optica", "glycan_involvement": "Glycosylation may affect antibody binding.", "mechanism": "Anti-MOG antibodies can be present in some NMO spectrum disorders.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8498413" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Glycosylation of \u03b22-glycoprotein I affects its antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are associated with antiphospholipid syndrome.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8498526" }, { "confidence": "medium", "disease": "myositis", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Presence of anti-\u03b22-glycoprotein I antibodies detected in patient with myositis post-COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8498526" }, { "confidence": "medium", "disease": "myositis", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for its function.", "mechanism": "Low C3 levels indicate complement activation in autoimmune myositis.", "protein": "complement C3", "relationship_type": "biomarker", "source_pmcid": "PMC8498526" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE-2 modulates viral binding and infectivity.", "mechanism": "ACE-2 is the entry receptor for SARS-CoV-2, facilitating infection.", "protein": "ACE-2", "relationship_type": "causal", "source_pmcid": "PMC8498526" }, { "confidence": "medium", "disease": "myositis", "glycan_involvement": "Glycosylation of ACE-2 may affect susceptibility of muscle cells to infection.", "mechanism": "Expression of ACE-2 on muscle cells may allow direct viral infection, triggering myositis.", "protein": "ACE-2", "relationship_type": "causal", "source_pmcid": "PMC8498526" }, { "confidence": "medium", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation affects antigenicity and antibody binding.", "mechanism": "Antibodies against beta-2 glycoprotein I are tested to rule out antiphospholipid syndrome in thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8503102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates spike binding affinity.", "mechanism": "SARS-CoV-2 binds to ACE2, mediating viral entry.", "protein": "ACE2 (Angiotensin-converting enzyme 2)", "relationship_type": "causal", "source_pmcid": "PMC8503102" }, { "confidence": "medium", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation may affect ACE2 stability and function.", "mechanism": "Downregulation of ACE2 by SARS-CoV-2 increases angiotensin II, promoting thrombosis.", "protein": "ACE2 (Angiotensin-converting enzyme 2)", "relationship_type": "causal", "source_pmcid": "PMC8503102" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune evasion.", "mechanism": "Spike protein mediates viral entry via ACE2.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC8503102" }, { "confidence": "medium", "disease": "Arterial thrombosis", "glycan_involvement": "Glycosylation affects receptor binding and immune recognition.", "mechanism": "Spike-ACE2 interaction triggers downstream prothrombotic pathways.", "protein": "SARS-CoV-2 Spike (S) protein", "relationship_type": "causal", "source_pmcid": "PMC8503102" }, { "confidence": "high", "disease": "antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects its antigenicity and interaction with autoantibodies.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for APS and contribute to hypercoagulability.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8503126" }, { "confidence": "medium", "disease": "deep venous thrombosis (DVT)", "glycan_involvement": "Glycosylation modulates immune recognition and prothrombotic activity.", "mechanism": "Autoantibodies to beta-2 glycoprotein I promote thrombosis in APS, leading to DVT.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8503126" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Spike protein glycosylation mediates cell entry and immune evasion", "mechanism": "Direct viral targeting of hepatobiliary cells leading to liver failure", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8503225" }, { "confidence": "medium", "disease": "Fulminant hepatic failure", "glycan_involvement": "Glycosylation affects P-glycoprotein drug transport function", "mechanism": "Inhibition of P-glycoprotein by amiodarone increases Remdesivir toxicity", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "causal (drug interaction)", "source_pmcid": "PMC8503225" }, { "confidence": "high", "disease": "Disseminated intravascular coagulation (DIC)", "glycan_involvement": "Glycosylation modulates fibrinogen stability and clotting", "mechanism": "Low fibrinogen levels indicate DIC in severe COVID-19/liver failure", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC8503225" }, { "confidence": "high", "disease": "Septic shock", "glycan_involvement": "Glycosylation influences IL-6 secretion and receptor binding", "mechanism": "Elevated IL-6 reflects cytokine storm and systemic inflammation", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC8503225" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Extensive glycosylation shields epitopes from immune detection", "mechanism": "Spike protein mediates viral entry and pathogenesis", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8503225" }, { "confidence": "high", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "MPO glycosylation may affect antigenicity and autoantibody binding.", "mechanism": "Anti-MPO IgG autoantibodies are diagnostic for AAV and mediate neutrophil activation and vascular injury.", "protein": "myeloperoxidase (MPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "high", "disease": "Diffuse Alveolar Hemorrhage (DAH)", "glycan_involvement": "Glycosylation may modulate MPO immune recognition.", "mechanism": "MPO autoantibodies trigger neutrophil-mediated capillaritis leading to DAH.", "protein": "myeloperoxidase (MPO)", "relationship_type": "causal", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation influences beta-2 glycoprotein I structure and immunogenicity.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are diagnostic for APS, which can cause pulmonary hemorrhage.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation may affect antigen presentation.", "mechanism": "Autoantibodies against phosphatidylserine-binding glycoproteins are associated with APS.", "protein": "phosphatidylserine-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune response.", "mechanism": "Spike glycoprotein mediates viral entry and immune activation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "ANCA-associated vasculitis (AAV)", "glycan_involvement": "Spike glycoprotein glycans may contribute to immune activation.", "mechanism": "COVID-19 infection may trigger autoimmune vasculitis via immune dysregulation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Anti-cardiolipin antibodies target glycoproteins involved in APS.", "protein": "cardiolipin-binding glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "MPO autoantibodies may be triggered or unmasked by SARS-CoV-2 infection.", "protein": "myeloperoxidase (MPO)", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "low", "disease": "Diffuse Alveolar Hemorrhage (DAH)", "glycan_involvement": "Glycosylation modulates immunogenicity.", "mechanism": "Anti-beta-2 glycoprotein I antibodies can be associated with DAH in APS.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8503401" }, { "confidence": "medium", "disease": "Diffuse Alveolar Hemorrhage (DAH)", "glycan_involvement": "Spike glycoprotein glycans may modulate host immune response.", "mechanism": "SARS-CoV-2 infection can directly cause DAH via endothelial injury.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8503401" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus infection (HIV/AIDS)", "glycan_involvement": "Dense N-glycan shield on Env protects virus from immune recognition and neutralizing antibodies.", "mechanism": "Mediates viral entry into host CD4+ T cells by binding CD4 and co-receptors; essential for infection.", "protein": "HIV Env glycoprotein (gp160/gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8506072" }, { "confidence": "high", "disease": "Human Immunodeficiency Virus infection (HIV/AIDS)", "glycan_involvement": "Glycosylation sites are targeted for drug and antibody binding; glycan shield modulates accessibility.", "mechanism": "Targeted by small molecules and antibodies to block viral entry; focus of vaccine and drug design.", "protein": "HIV Env glycoprotein (gp160/gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8506072" }, { "confidence": "medium", "disease": "Human Immunodeficiency Virus infection (HIV/AIDS)", "glycan_involvement": "Glycosylation affects antigenicity and detection by immune assays.", "mechanism": "Presence of Env glycoprotein on viral particles and infected cells is used for diagnosis and monitoring.", "protein": "HIV Env glycoprotein (gp160/gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8506072" }, { "confidence": "high", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation may modulate membrane binding and mineral nucleation efficiency.", "mechanism": "Annexin A5 in matrix vesicles binds to collagen and DPPS, facilitating nucleation and propagation of mineralization in vascular smooth muscle cells.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "high", "disease": "Bone mineralization disorders", "glycan_involvement": "Glycosylation may affect membrane localization and Ca2+ binding.", "mechanism": "Annexin A6 localizes to distinct regions of matrix vesicle membranes, interacting with cholesterol and Ca2+, regulating physiological mineralization.", "protein": "Annexin A6", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "ANXA6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08133" }, "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "high", "disease": "Ectopic mineralization", "glycan_involvement": "Glycosylation influences enzyme activity and membrane anchoring.", "mechanism": "TNAP in matrix vesicles hydrolyzes ATP/PPi to produce inorganic phosphate, driving pathological mineralization in soft tissues.", "protein": "Tissue Non-specific Alkaline Phosphatase (TNAP)", "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Ectopic mineralization", "glycan_involvement": "Glycosylation may affect membrane orientation and activity.", "mechanism": "Na,K-ATPase in matrix vesicles can hydrolyze ATP, contributing to mineral propagation as a backup pathway when TNAP is inhibited.", "protein": "Na,K-ATPase", "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "high", "disease": "Bone mineralization disorders", "glycan_involvement": "Glycosylation may regulate membrane association and mineral nucleation.", "mechanism": "Annexin A5 stabilizes DPPS-enriched domains in the presence of Ca2+, retarding vesicle fusion and facilitating mineral nucleation.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Ectopic mineralization", "glycan_involvement": "Glycosylation status may affect therapeutic efficacy.", "mechanism": "Proteoliposomes mimicking matrix vesicles with Annexin A5 can be used to study and potentially inhibit ectopic calcification.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8551951" }, { "confidence": "high", "disease": "Bone mineralization disorders", "glycan_involvement": "Glycosylation affects enzyme stability and function.", "mechanism": "Mutations in TNAP alter catalytic efficiency and mineral propagation, impacting bone mineralization.", "protein": "Tissue Non-specific Alkaline Phosphatase (TNAP)", "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Bacterial infection (Salmonella resistance)", "glycan_involvement": "Glycosylation may modulate membrane insertion and proteolytic activity.", "mechanism": "PgtE cleaves host antimicrobial peptides, conferring resistance to host defense and promoting infection.", "protein": "PgtE protease", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8Z4F3" }, "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Sickle cell disease", "glycan_involvement": "Glycosylation may affect binding affinity to PS.", "mechanism": "Annexin V (A5) binds to phosphatidylserine exposed on eryptotic erythrocytes, which adhere to endothelium in sickle cell disease.", "protein": "Annexin A5", "protein_enriched": { "function": "This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade", "gene_name": "ANXA5", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P08758" }, "relationship_type": "biomarker", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Vascular calcification", "glycan_involvement": "Glycosylation may regulate membrane localization and function.", "mechanism": "Annexin A6 interacts with cholesterol and Ca2+ in matrix vesicles, modulating mineralization in vascular tissues.", "protein": "Annexin A6", "protein_enriched": { "function": "May associate with CD21. May regulate the release of Ca(2+) from intracellular stores", "gene_name": "ANXA6", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G41247ZX" ], "uniprot_id": "P08133" }, "relationship_type": "causal", "source_pmcid": "PMC8551951" }, { "confidence": "medium", "disease": "Cerebral venous sinus thrombosis (CVST)", "glycan_involvement": "Spike is heavily glycosylated, which affects immune recognition and function.", "mechanism": "Spike protein binds ACE2, triggers endothelial damage and coagulation cascade.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8562696" }, { "confidence": "medium", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "Glycosylation may influence immunogenicity and mimicry.", "mechanism": "Vaccine-encoded spike glycoprotein may act as a polyanion, promoting PF4 antibody formation.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8562696" }, { "confidence": "high", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "PF4 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Anti-PF4 antibodies trigger platelet activation, thrombosis, and thrombocytopenia.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC8562696" }, { "confidence": "high", "disease": "Heparin-induced thrombocytopenia (HIT)", "glycan_involvement": "Glycosylation may modulate immunogenicity of PF4.", "mechanism": "PF4/heparin complexes induce antibody formation, leading to platelet activation.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC8562696" }, { "confidence": "medium", "disease": "Vaccine-induced immune thrombotic thrombocytopenia (VITT)", "glycan_involvement": "IgG Fc glycosylation modulates effector function.", "mechanism": "Anti-PF4 IgG mediates platelet activation via Fc\u03b3RIIa, causing thrombosis.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC8562696" }, { "confidence": "high", "disease": "Thrombocytopenia", "glycan_involvement": "PF4 glycosylation may affect clearance.", "mechanism": "Anti-PF4 antibodies cause platelet consumption and depletion.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "causal", "source_pmcid": "PMC8562696" }, { "confidence": "low", "disease": "Thrombosis", "glycan_involvement": "CD147 is a highly glycosylated receptor.", "mechanism": "CD147 implicated in thrombosis in other viral infections; possible role in COVID-19.", "protein": "CD147 (Basigin)", "relationship_type": "causal (hypothesized)", "source_pmcid": "PMC8562696" }, { "confidence": "low", "disease": "Disseminated intravascular coagulation", "glycan_involvement": "Glycosylation shields spike from immune detection, modulating response.", "mechanism": "Spike-induced immune activation may trigger systemic coagulation.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8562696" }, { "confidence": "medium", "disease": "Disseminated intravascular coagulation", "glycan_involvement": "Glycosylation may affect antibody recognition.", "mechanism": "Anti-PF4 antibodies associated with severe coagulopathy.", "protein": "Platelet Factor 4 (PF4)", "protein_enriched": { "function": "Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed", "gene_name": "PF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02776" }, "relationship_type": "biomarker", "source_pmcid": "PMC8562696" }, { "confidence": "high", "disease": "Heparin-induced thrombocytopenia (HIT)", "glycan_involvement": "Fc glycosylation critical for effector function.", "mechanism": "Anti-PF4/heparin IgG mediates platelet activation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC8562696" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 and membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "Multisystem Inflammatory Syndrome in Children (MIS-C)", "glycan_involvement": "O-glycans near furin cleavage site may influence superantigen activity.", "mechanism": "Superantigen-like region in S protein triggers abnormal T cell activation.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation may shield or expose superantigenic motifs.", "mechanism": "Superantigenic activity of S protein induces excessive immune activation.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "Toxic Shock Syndrome (TSS)-like illness", "glycan_involvement": "O-glycosylation at S1/S2 junction may modulate superantigen exposure.", "mechanism": "Superantigen-like region in S protein mimics bacterial superantigens, causing TSS-like symptoms.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8564281" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Target for neutralizing antibodies and vaccines.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 may affect S protein binding.", "mechanism": "Host receptor for S protein, mediates viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "SP-D is a collectin with glycan-binding activity.", "mechanism": "Recombinant SP-D (AT-100) reduces lung inflammation and viral infection.", "protein": "Surfactant protein D (SP-D)", "relationship_type": "protective", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity.", "mechanism": "Detection of S protein or anti-S antibodies used for diagnosis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8564281" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation can mask or expose neutralizing epitopes.", "mechanism": "Monoclonal antibodies (e.g., CR3022, B38, H4) target S protein RBD.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8564281" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "O-glycans at S1/S2 junction may regulate cleavage efficiency.", "mechanism": "Furin cleavage site in S protein is a target for protease inhibitors.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8564281" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition", "mechanism": "Mediates viral entry via ACE2 binding; target for neutralization", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8573676" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Furin is glycosylated, affecting its stability and localization", "mechanism": "Cleaves S protein at polybasic site, enabling viral entry; phytochemicals inhibit Furin", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, influencing S protein binding", "mechanism": "Host receptor for S protein; phytochemicals may block S-ACE2 interaction", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Binds high-mannose N-glycans on viral envelope", "mechanism": "Plant lectin binds viral glycoproteins, blocking viral attachment", "protein": "Urtica dioica agglutinin (UDA)", "protein_enriched": { "function": "Glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that interacts via its N-terminal immunoglobulin domain with cell surface receptors including 2B4/CD244 or CD2 to regulate immune ", "gene_name": "Cd48", "glycan_count": 34, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00176HZ", "G00670OT", "G06110VR", "G07483YN", "G14669DU", "G22768VO", "G23432EQ", "G27919IH", "G29011JC", "G31544HA", "G31936TA", "G36134VO", "G36191CD", "G39213VZ", "G40124HY", "G46687AB", "G49874UX", "G50045TK", "G50757KG", "G55220VL", "G58667NI", "G63889NK", "G70375MX", "G72797UR", "G74724QE", "G77149EE", "G79568CQ", "G80858MF", "G82348BZ", "G86357DX", "G89098OM", "G90093AU", "G90426CG", "G94854LT" ], "uniprot_id": "P10252" }, "relationship_type": "protective", "source_pmcid": "PMC8573676" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Heavily N-glycosylated; glycans shield from immune system", "mechanism": "Mediates viral entry via CD4; target for antiviral phytochemicals", "protein": "HIV gp120", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation required for secretion and infectivity", "mechanism": "Surface antigen used for diagnosis; cleared by phytochemicals (Phyllanthus amarus)", "protein": "HBsAg", "protein_enriched": { "function": "Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller", "gene_name": "C", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03147" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "medium", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor binding", "mechanism": "Envelope glycoprotein mediates entry; inhibited by plant extracts", "protein": "HCV E2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation shields epitopes, modulates infectivity", "mechanism": "Mediates viral entry; target for phytochemicals and lectins", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8573676" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation affects function", "mechanism": "Structural protein involved in assembly and pathogenesis", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC8573676" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assembly and immune evasion", "mechanism": "Structural protein critical for viral assembly", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC8573676" }, { "confidence": "high", "disease": "Mevalonate kinase deficiency (MKD)", "glycan_involvement": "Glycosylation affects SAA stability and function as an acute phase reactant.", "mechanism": "SAA levels reflect systemic inflammation and disease activity in MKD.", "protein": "Serum amyloid A (SAA)", "protein_enriched": { "function": "Major acute phase protein", "gene_name": "SAA1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DJI8" }, "relationship_type": "biomarker", "source_pmcid": "PMC8574945" }, { "confidence": "high", "disease": "Mevalonate kinase deficiency (MKD)", "glycan_involvement": "CRP is a glycoprotein; glycosylation is essential for its solubility and function.", "mechanism": "CRP is used to monitor inflammation and response to therapy in MKD.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8574945" }, { "confidence": "high", "disease": "Cryopyrin-associated periodic syndromes (CAPS)", "glycan_involvement": "Glycosylation modulates IL-1\u03b2 secretion and stability.", "mechanism": "IL-1\u03b2 overproduction drives autoinflammation in CAPS.", "protein": "Interleukin-1 beta (IL-1\u03b2)", "protein_enriched": { "function": "Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-", "gene_name": "Il1b", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P10749" }, "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "medium", "disease": "Cryopyrin-associated periodic syndromes (CAPS)", "glycan_involvement": "NLRP3 is glycosylated; splicing variants may affect glycosylation and function.", "mechanism": "NLRP3 mutations activate inflammasome, leading to IL-1\u03b2 release.", "protein": "NLRP3", "protein_enriched": { "function": "Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyropt", "gene_name": "NLRP3", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q96P20" }, "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "high", "disease": "Pulmonary alveolar proteinosis (PAP)", "glycan_involvement": "OAS1 is glycosylated, which may affect its localization and activity.", "mechanism": "OAS1 gain-of-function mutation causes dsRNA-independent activation, leading to PAP.", "protein": "OAS1", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular process", "gene_name": "OAS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00973" }, "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "medium", "disease": "Hypogammaglobulinemia", "glycan_involvement": "Glycosylation may influence OAS1 stability in immune cells.", "mechanism": "OAS1 GOF leads to B-cell apoptosis and hypogammaglobulinemia.", "protein": "OAS1", "protein_enriched": { "function": "Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular process", "gene_name": "OAS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P00973" }, "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "high", "disease": "Hypogammaglobulinemia", "glycan_involvement": "IgG Fc glycosylation modulates immune effector functions.", "mechanism": "Low IgG is a diagnostic marker for hypogammaglobulinemia.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8574945" }, { "confidence": "medium", "disease": "Fibrodysplasia ossificans progressiva (FOP)", "glycan_involvement": "ACVR1 is a glycoprotein receptor; glycosylation may affect ligand binding.", "mechanism": "ACVR1 gain-of-function mutations drive heterotopic ossification.", "protein": "ACVR1", "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "medium", "disease": "Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)", "glycan_involvement": "TNFR glycosylation is important for receptor function and trafficking.", "mechanism": "Mutations in TNFR1 lead to defective receptor shedding and autoinflammation.", "protein": "Tumor necrosis factor receptor (TNFR)", "relationship_type": "causal", "source_pmcid": "PMC8574945" }, { "confidence": "medium", "disease": "Hypogammaglobulinemia", "glycan_involvement": "IgA glycosylation affects mucosal immunity.", "mechanism": "Absent IgA is a feature of hypogammaglobulinemia in OAS1 GOF disease.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC8574945" }, { "confidence": "high", "disease": "Cardiovascular diseases", "glycan_involvement": "MPO is a glycoprotein; glycosylation affects stability and secretion.", "mechanism": "MPO promotes inflammation via HOCl production; inhibition reduces inflammation.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Neurodegenerative diseases", "glycan_involvement": "Glycosylation modulates MPO function.", "mechanism": "MPO-driven oxidative stress implicated in neurodegeneration.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "COVID-19 (SARS)", "glycan_involvement": "Glycosylation may affect MPO's immune interactions.", "mechanism": "MPO activity contributes to inflammatory damage in severe COVID-19.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "high", "disease": "Gouty arthritis", "glycan_involvement": "Glycosylation required for MPO secretion and function.", "mechanism": "MPO inhibition reduces inflammation and edema in arthritis models.", "protein": "Myeloperoxidase (MPO)", "protein_enriched": { "function": "Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of h", "gene_name": "MPO", "glycan_count": 77, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G83460ZZ", "G49108TO", "G00912UN", "G02815KT", "G05724UK", "G06110VR", "G06247RL", "G11629QQ", "G11870QZ", "G15169WU", "G29299MO", "G31852PQ", "G33609NS", "G34989PA", "G39188ZX", "G41247ZX", "G47518TP", "G47644PP", "G48414YA", "G62765YT", "G80920RR", "G90093AU", "G90575OW", "G92050GC", "G92275SC", "G94917XT", "G09724ZC", "G22573RC", "G22768VO", "G25541YH", "G27947YN", "G28681TP", "G37881RL", "G40574BA", "G52527GH", "G55220VL", "G56014GC", "G56784JY", "G59536GA", "G75983OB", "G80966KZ", "G81315DD", "G82020ZR", "G01650EU", "G14669DU", "G25637MV", "G35697OJ", "G37399XV", "G74724QE", "G00395TQ", "G05049YU", "G06356OH", "G08290VR", "G08293MJ", "G11314AS", "G18647XP", "G22310AV", "G23719VF", "G27058EU", "G29880MM", "G36379GD", "G40926MX", "G42466VF", "G45889JQ", "G49874UX", "G50282JC", "G59626AS", "G63041LO", "G77547TA", "G82348BZ", "G84349RE", "G84452RH", "G85269DF", "G88374WZ", "G94854LT", "G95865ZB", "G96091TT" ], "uniprot_id": "P05164" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Cutaneous melanoma", "glycan_involvement": "Opsins are glycoproteins; glycosylation affects trafficking and signaling.", "mechanism": "Opsins regulate pigmentary and apoptosis-related processes in melanoma cells.", "protein": "Opsins (OPN4, OPN3, OPN5)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Epilepsy", "glycan_involvement": "Glycosylation modulates channel gating and drug sensitivity.", "mechanism": "Sodium channels are drug targets for seizure control.", "protein": "Voltage-gated sodium channel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Cardiac conditions", "glycan_involvement": "Glycosylation affects channel localization and function.", "mechanism": "Channel dysfunction causes arrhythmias; drugs target glycosylated channels.", "protein": "Voltage-gated sodium channel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Pain diseases", "glycan_involvement": "Glycosylation modulates channel activity.", "mechanism": "Channel blockers used for pain; glycosylation alters pharmacology.", "protein": "Voltage-gated sodium channel", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Staphylococcus aureus infection (\u03b2-lactam resistance)", "glycan_involvement": "Glycosylation may affect sensor function and antibiotic binding.", "mechanism": "These glycoproteins sense \u03b2-lactam antibiotics and activate resistance pathways.", "protein": "BlaR1/MecR1/VraS", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8580805" }, { "confidence": "medium", "disease": "Pigmentation disorders", "glycan_involvement": "Glycosylation required for opsin function.", "mechanism": "Opsins regulate skin pigmentation via light sensing.", "protein": "Opsins (OPN4, OPN3, OPN5)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8580805" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity and antibody recognition.", "mechanism": "Anti-MOG antibodies are associated with a subset of NMOSD cases, indicating immune-mediated demyelination.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is glycosylated; glycosylation may influence antibody binding and pathogenicity.", "mechanism": "Anti-AQP4 antibodies are a diagnostic marker for NMOSD, mediating astrocyte injury.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation of MOG may modulate immune recognition.", "mechanism": "Anti-MOG antibodies are linked to optic neuritis, especially in bilateral or recurrent cases.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation may affect AQP4 antigenicity.", "mechanism": "Anti-AQP4 antibodies can be present in optic neuritis as part of NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Longitudinally extensive transverse myelitis", "glycan_involvement": "Glycosylation may influence MOG's immunogenicity.", "mechanism": "Anti-MOG antibodies are associated with myelitis, especially in seronegative NMOSD.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Longitudinally extensive transverse myelitis", "glycan_involvement": "Glycosylation may modulate antibody binding.", "mechanism": "Anti-AQP4 antibodies are linked to myelitis in NMOSD.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may alter MOG's antigenic properties.", "mechanism": "Autoimmunity against MOG can cause demyelination in NMOSD-like syndromes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8592852" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may affect AQP4's immune recognition.", "mechanism": "Anti-AQP4 antibodies mediate astrocyte damage, leading to NMOSD pathology.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "causal", "source_pmcid": "PMC8592852" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation of HA affects receptor binding and immune evasion.", "mechanism": "HA mediates viral entry into host cells by binding to sialic acid-containing glycans on host cell surfaces.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates NA enzymatic activity and antigenicity.", "mechanism": "NA cleaves sialic acids to facilitate viral release from infected cells; targeted by antiviral drugs.", "protein": "Neuraminidase (NA)", "protein_enriched": { "function": "Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus re", "gene_name": "NA", "glycan_count": 0, "glycosylation_sites_count": 5, "glytoucan_ids": [], "uniprot_id": "P03468" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "S protein mediates SARS-CoV-2 entry via ACE2 receptor binding.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Target of neutralizing antibodies and vaccines.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycan shield on gp120 impedes antibody recognition.", "mechanism": "gp120/gp41 mediate viral entry into CD4+ T cells.", "protein": "HIV envelope glycoprotein (gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation patterns influence immune evasion and vaccine efficacy.", "mechanism": "Target for broadly neutralizing antibodies and vaccine development.", "protein": "HIV envelope glycoprotein (gp120/gp41)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation affects antigenicity and detection.", "mechanism": "HBsAg is used for diagnosis and monitoring of infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC8607884" }, { "confidence": "medium", "disease": "Measles", "glycan_involvement": "Glycosylation modulates infectivity and immune response.", "mechanism": "Envelope glycoproteins mediate viral entry and cell fusion.", "protein": "Measles virus envelope glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "medium", "disease": "Rabies", "glycan_involvement": "Glycosylation influences neurotropism and immunogenicity.", "mechanism": "Glycoprotein mediates viral attachment and entry into neurons.", "protein": "Rabies virus glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "medium", "disease": "Pertussis", "glycan_involvement": "Glycosylation affects toxin activity and immune recognition.", "mechanism": "Pertussis toxin is a key virulence factor in Bordetella pertussis infection.", "protein": "Pertussis toxin (glycoprotein subunit)", "relationship_type": "causal", "source_pmcid": "PMC8607884" }, { "confidence": "high", "disease": "Dermatomyositis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects stability and function", "mechanism": "Elevated in inflammatory states including dermatomyositis", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "high", "disease": "Dermatomyositis", "glycan_involvement": "ANA are immunoglobulins with N-glycosylation affecting immune recognition", "mechanism": "Presence indicates autoimmune activity in dermatomyositis", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "high", "disease": "Dermatomyositis", "glycan_involvement": "Immunoglobulin glycosylation modulates effector function", "mechanism": "Specific autoantibody associated with myositis subset", "protein": "Anti-JO1 antibody", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "medium", "disease": "Venous thrombosis", "glycan_involvement": "Immunoglobulin glycosylation may affect pathogenicity", "mechanism": "Autoantibody linked to increased thrombosis risk", "protein": "Cardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "high", "disease": "Dermatomyositis", "glycan_involvement": "CK is glycosylated, which may affect serum stability", "mechanism": "Elevated in muscle damage including dermatomyositis", "protein": "Creatine kinase", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "medium", "disease": "Dermatomyositis", "glycan_involvement": "LDH is glycosylated, influencing serum half-life", "mechanism": "Elevated in tissue damage and inflammation", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates CRP's immune functions", "mechanism": "Elevated in acute COVID-19 infection", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation may influence autoimmunity", "mechanism": "Autoantibodies may be induced post-infection", "protein": "Antinuclear antibodies (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation may modulate pathogenicity", "mechanism": "COVID-19 may trigger anti-JO1 autoimmunity", "protein": "Anti-JO1 antibody", "relationship_type": "causal", "source_pmcid": "PMC8610734" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation affects CRP's inflammatory role", "mechanism": "Elevated CRP is associated with thrombotic complications", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8610734" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and affects receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8638150" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates spike binding and viral entry efficiency.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via interaction with spike glycoprotein.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC8638150" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP levels indicate inflammation and disease severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IL-6 is glycosylated, which affects its secretion and activity.", "mechanism": "IL-6 is elevated in severe cases, contributing to cytokine storm and inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation is important for IFN-\u03b2 stability and bioactivity.", "mechanism": "IFN-\u03b2 reduces viral replication in vitro and is used in combination therapy.", "protein": "Interferon-beta (IFN-\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG glycosylation modulates effector functions and anti-inflammatory activity.", "mechanism": "IVIG therapy used for immune modulation in severe cases.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects IL-10 secretion and stability.", "mechanism": "Elevated IL-10 reflects immune dysregulation in severe disease.", "protein": "Interleukin-10 (IL-10)", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "Il10", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P18893" }, "relationship_type": "biomarker", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates IL-7 activity.", "mechanism": "IL-7 is elevated in severe cases, indicating immune activation.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects TNF-\u03b1 secretion and receptor binding.", "mechanism": "TNF-\u03b1 is part of the cytokine storm in severe COVID-19.", "protein": "Tumor necrosis factor alpha (TNF-\u03b1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8638150" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation shields spike protein from immune recognition.", "mechanism": "Spike protein mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8638150" }, { "confidence": "medium", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "CCL23 is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated in severe CAP, indicating increased monocyte recruitment.", "protein": "CCL23", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "medium", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "MCP-3 is glycosylated, which can modulate receptor interactions.", "mechanism": "Higher in severe CAP, reflecting enhanced chemotactic signaling.", "protein": "MCP-3 (CCL7)", "protein_enriched": { "function": "Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity. Also induces the release of gelatinase B. This protein can bind heparin. Binds t", "gene_name": "CCL7", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P80098" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "high", "disease": "Viral CAP", "glycan_involvement": "IL-6 is glycosylated, influencing secretion and activity.", "mechanism": "Increased in viral CAP, especially influenza, indicating robust proinflammatory response.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "high", "disease": "Viral CAP", "glycan_involvement": "TNF is glycosylated, affecting receptor binding.", "mechanism": "Elevated in viral CAP, especially influenza, reflecting inflammation.", "protein": "TNF", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "medium", "disease": "Influenza-associated CAP", "glycan_involvement": "IFN-\u03b3 is glycosylated, which may affect stability.", "mechanism": "Higher in influenza CAP, indicating antiviral immune activation.", "protein": "IFN-\u03b3", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "medium", "disease": "Influenza-associated CAP", "glycan_involvement": "IP-10 is glycosylated, modulating chemotactic function.", "mechanism": "Increased in influenza CAP, reflecting antiviral chemokine response.", "protein": "IP-10 (CXCL10)", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "high", "disease": "Influenza-associated CAP", "glycan_involvement": "Glycosylation affects IL-6 secretion and receptor interaction.", "mechanism": "Significantly higher in influenza CAP than atypical bacterial CAP.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "medium", "disease": "Influenza-associated CAP", "glycan_involvement": "All MCPs are glycoproteins; glycosylation modulates chemotactic activity.", "mechanism": "Elevated in influenza CAP compared to atypical bacterial CAP.", "protein": "MCP1-4", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "high", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "Glycosylation influences IL-6 function.", "mechanism": "Correlates with disease severity and viral etiology.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "medium", "disease": "Community Acquired Pneumonia (CAP)", "glycan_involvement": "Glycosylation may affect chemokine gradient formation.", "mechanism": "Distinguishes severe from mild CAP.", "protein": "CCL23", "relationship_type": "biomarker", "source_pmcid": "PMC8644307" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus (RSV) infection", "glycan_involvement": "Glycosylation of F protein is essential for proper folding and function.", "mechanism": "RSV F glycoprotein mediates viral entry and fusion with host cells, enabling infection.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8644347" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus (RSV) infection", "glycan_involvement": "Antibody glycosylation extends half-life and may affect effector function.", "mechanism": "MK-1654 binds RSV F glycoprotein, neutralizing the virus and preventing infection.", "protein": "MK-1654 (anti-RSV F monoclonal antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8644347" }, { "confidence": "high", "disease": "RSV-associated medically attended lower respiratory tract infection", "glycan_involvement": "Fc glycosylation of MK-1654 contributes to extended half-life.", "mechanism": "Prophylactic administration reduces incidence of lower respiratory tract infection in infants.", "protein": "MK-1654 (anti-RSV F monoclonal antibody)", "relationship_type": "protective", "source_pmcid": "PMC8644347" }, { "confidence": "high", "disease": "Respiratory Syncytial Virus (RSV) infection", "glycan_involvement": "Antibody glycosylation may influence pharmacokinetics.", "mechanism": "REGN-2222 neutralizes RSV by binding F glycoprotein, preventing viral entry.", "protein": "REGN-2222 (anti-RSV F monoclonal antibody)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8644347" }, { "confidence": "high", "disease": "RSV-associated medically attended lower respiratory tract infection", "glycan_involvement": "Glycosylation is necessary for F protein function and immune evasion.", "mechanism": "F glycoprotein is required for RSV to infect lower respiratory tract cells.", "protein": "RSV F glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8644347" }, { "confidence": "high", "disease": "Intestinal necrosis", "glycan_involvement": "Complement proteins are glycosylated, affecting their stability and function.", "mechanism": "Complement activation drives inflammatory damage after intestinal wall compromise.", "protein": "Complement proteins (classical and lectin pathway)", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "Intestinal perforation", "glycan_involvement": "Glycosylation modulates complement protein activity.", "mechanism": "Complement activation promotes immune cell recruitment and tissue injury.", "protein": "Complement proteins (classical and lectin pathway)", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "medium", "disease": "Bacterial sepsis", "glycan_involvement": "Glycosylation affects complement protein clearance and immune recognition.", "mechanism": "Complement activation enhances systemic inflammation and sepsis risk.", "protein": "Complement proteins (classical and lectin pathway)", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "medium", "disease": "Intestinal necrosis", "glycan_involvement": "Myeloperoxidase glycosylation influences enzyme stability and secretion.", "mechanism": "Neutrophil myeloperoxidase activity contributes to tissue damage via oxidative stress.", "protein": "Myeloperoxidase", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "medium", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation modulates myeloperoxidase immune interactions.", "mechanism": "Excessive myeloperoxidase activity drives systemic inflammation.", "protein": "Myeloperoxidase", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "Intestinal necrosis", "glycan_involvement": "IL-6 glycosylation affects receptor binding and signaling.", "mechanism": "Elevated IL-6 reflects inflammatory response to tissue injury.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation modulates IL-6 stability and bioactivity.", "mechanism": "High IL-6 levels indicate systemic inflammation.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "Systemic inflammatory response syndrome (SIRS)", "glycan_involvement": "Glycosylation regulates complement protein interactions.", "mechanism": "Complement activation triggers cytokine release and systemic inflammation.", "protein": "Complement proteins (classical and lectin pathway)", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "medium", "disease": "Bacterial sepsis", "glycan_involvement": "Glycosylation affects myeloperoxidase localization and activity.", "mechanism": "Neutrophil myeloperoxidase contributes to pathogen killing and collateral tissue damage.", "protein": "Myeloperoxidase", "relationship_type": "causal", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "Intestinal necrosis", "glycan_involvement": "Targeting glycosylated complement proteins modulates immune response.", "mechanism": "Inhibition by RLS-0071 improves survival by reducing complement-mediated injury.", "protein": "Complement proteins (classical and lectin pathway)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8644475" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans shield epitopes, modulate receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2; highly glycosylated, facilitating immune evasion and host cell attachment.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates S protein interaction.", "mechanism": "Host receptor for SARS-CoV-2 S protein; glycosylation affects binding affinity.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8654706" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential O-glycosylation; not fully characterized.", "mechanism": "Induces TLR2/NF-\u03baB and MAPK signaling, leading to endothelial activation and cytokine storm.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation required for function and ligand binding.", "mechanism": "Upregulated in severe COVID-19; mediates leukocyte adhesion and infiltration.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates adhesion properties.", "mechanism": "Elevated in severe COVID-19; promotes immune cell infiltration and inflammation.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC8654706" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation influences protease stability.", "mechanism": "Host protease primes S protein for viral entry; glycosylation may affect localization/activity.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated.", "mechanism": "Essential for viral polyprotein processing; targeted by herbal inhibitors.", "protein": "3CLpro (Mpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated.", "mechanism": "Processes viral polyproteins and antagonizes host immune response.", "protein": "PLpro", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8654706" }, { "confidence": "medium", "disease": "ARDS", "glycan_involvement": "Extracellular HMGB1 interacts with glycan receptors (e.g., RAGE).", "mechanism": "Released during NLRP3 inflammasome activation; drives inflammation and tissue injury.", "protein": "HMGB1", "protein_enriched": { "function": "Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone ", "gene_name": "HMGB1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G04854VP", "G28541PG", "G75230KT" ], "uniprot_id": "P09429" }, "relationship_type": "biomarker", "source_pmcid": "PMC8654706" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates immune recognition and endothelial interactions.", "mechanism": "S protein-induced endothelial damage and platelet activation contribute to immunothrombosis.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8654706" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein is essential for receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation modulates spike-ACE2 interaction.", "mechanism": "Spike protein binds ACE2, which is highly expressed in hypertensive patients, increasing susceptibility.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation affects spike protein stability and host immune response.", "mechanism": "Spike-ACE2 interaction may exacerbate inflammation in diabetic patients.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Heart problems", "glycan_involvement": "Glycosylation influences spike protein's tropism and immune evasion.", "mechanism": "Spike-ACE2 binding may worsen cardiovascular conditions.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "high", "disease": "Respiratory problems", "glycan_involvement": "Glycosylation is critical for spike function in respiratory tract infection.", "mechanism": "Spike protein enables viral entry into respiratory epithelium.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates spike binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2, facilitating infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect ACE2 expression and function.", "mechanism": "ACE2 is upregulated in hypertension, increasing COVID-19 susceptibility.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Type 2 diabetes", "glycan_involvement": "Glycosylation status may modulate ACE2 activity.", "mechanism": "ACE2 expression is altered in diabetes, influencing COVID-19 risk.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8678259" }, { "confidence": "medium", "disease": "Heart problems", "glycan_involvement": "Glycosylation impacts ACE2's interaction with spike protein.", "mechanism": "ACE2 is involved in cardiovascular regulation and is a target for SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8678259" }, { "confidence": "high", "disease": "Respiratory problems", "glycan_involvement": "Glycosylation affects ACE2 localization and spike binding.", "mechanism": "ACE2 is highly expressed in respiratory epithelium, mediating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8678259" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Sotrovimab is an IgG1 glycoprotein; its Fc glycosylation affects effector function and half-life.", "mechanism": "Sotrovimab binds to a conserved epitope on the SARS-CoV-2 spike glycoprotein, neutralizing the virus and preventing cell entry.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which affects spike binding affinity.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2 spike protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "IgG glycosylation may influence efficacy in metabolic disease contexts.", "mechanism": "Sotrovimab is effective in COVID-19 patients with diabetes, reducing progression to severe disease.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "Chronic kidney disease", "glycan_involvement": "Glycosylation may affect pharmacokinetics in renal impairment.", "mechanism": "Sotrovimab reduces COVID-19 progression in patients with CKD.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "No direct evidence, but IgG glycosylation may modulate immune response.", "mechanism": "Sotrovimab is effective in COVID-19 patients with hypertension, reducing severe outcomes.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "Bronchial asthma", "glycan_involvement": "No direct evidence; general IgG glycosylation effects possible.", "mechanism": "Sotrovimab reduces COVID-19 progression in patients with asthma.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "No direct evidence; general IgG glycosylation effects possible.", "mechanism": "Sotrovimab is effective in COVID-19 patients with IHD, reducing progression.", "protein": "Sotrovimab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation of IgG1 modulates effector function and serum half-life.", "mechanism": "Early administration of sotrovimab in mild/moderate COVID-19 reduces hospitalization and improves clinical/lab markers.", "protein": "Sotrovimab", "relationship_type": "protective", "source_pmcid": "PMC8685821" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans on spike modulate antibody accessibility and neutralization.", "mechanism": "Spike protein is the target of neutralizing antibodies including sotrovimab.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8685821" }, { "confidence": "high", "disease": "GFAP astrocytopathy (GFAP-A)", "glycan_involvement": "GFAP is not a glycoprotein; no glycosylation involvement.", "mechanism": "GFAP autoantibody in CSF is a marker of disease; pathogenesis involves cytotoxic T cell response to GFAP peptides.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "GFAP astrocytopathy (GFAP-A)", "glycan_involvement": "Spike protein is a glycoprotein; glycosylation may affect immunogenicity and cross-reactivity.", "mechanism": "mRNA vaccine encoding spike protein may trigger autoimmunity via bystander activation or molecular mimicry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (hypothetical trigger)", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "Autoimmune encephalitis", "glycan_involvement": "Glycosylation of spike protein may influence immune recognition.", "mechanism": "Cross-reactivity of spike protein antibodies with human CNS proteins may trigger autoimmunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (hypothetical trigger)", "source_pmcid": "PMC8694819" }, { "confidence": "medium", "disease": "Myelitis", "glycan_involvement": "MOG is a glycoprotein; glycosylation is important for antigenicity.", "mechanism": "Anti-MOG antibodies are tested to rule out MOG-associated disease.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8694819" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "Beta-2 glycoprotein I is N-glycosylated; glycosylation affects immune recognition.", "mechanism": "Anti-beta-2 glycoprotein I antibodies tested to exclude antiphospholipid syndrome.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "Myocarditis", "glycan_involvement": "Spike protein glycosylation may modulate immune response.", "mechanism": "mRNA vaccine may rarely trigger myocarditis via immune activation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (hypothetical trigger)", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "Multisystem inflammatory syndrome", "glycan_involvement": "Glycosylation may influence immunogenicity.", "mechanism": "mRNA vaccine may rarely trigger systemic inflammation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (hypothetical trigger)", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "Autoimmune encephalitis", "glycan_involvement": "S100B is not a glycoprotein; no glycan involvement.", "mechanism": "Spike protein antibodies may cross-react with S100B, contributing to CNS autoimmunity.", "protein": "S100B", "protein_enriched": { "function": "Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:20950652, PubMed:6487634). Weakly binds c", "gene_name": "S100B", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04271" }, "relationship_type": "causal (hypothetical, via cross-reactivity)", "source_pmcid": "PMC8694819" }, { "confidence": "low", "disease": "Autoimmune encephalitis", "glycan_involvement": "MBP is not a glycoprotein; no glycan involvement.", "mechanism": "Spike protein antibodies may cross-react with MBP, contributing to CNS autoimmunity.", "protein": "Myelin basic protein (MBP)", "protein_enriched": { "function": "The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. ", "gene_name": "MBP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P02686" }, "relationship_type": "causal (hypothetical, via cross-reactivity)", "source_pmcid": "PMC8694819" }, { "confidence": "medium", "disease": "Meningoencephalitis", "glycan_involvement": "GFAP is not glycosylated.", "mechanism": "GFAP autoantibody in CSF supports diagnosis of immune-mediated meningoencephalitis.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC8694819" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, affecting antigenicity and immune recognition.", "mechanism": "Induces T-cell and humoral immune responses post-vaccination, contributing to protection against infection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Acute myeloblastic leukemia", "glycan_involvement": "Glycosylation may modulate immune detection in these patients.", "mechanism": "Used to assess vaccine-induced immune response in immunocompromised patients.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Myelodysplastic syndrome", "glycan_involvement": "Glycosylation influences immunogenicity.", "mechanism": "Used to evaluate vaccine response in patients post-transplant.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Epstein-Barr Virus (EBV) infection", "glycan_involvement": "Viral glycoproteins are targets for T-cell recognition.", "mechanism": "EBV-specific T-cell responses serve as a control for immune competence.", "protein": "EBV glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Cytomegalovirus (CMV) infection", "glycan_involvement": "Glycoproteins mediate immune recognition.", "mechanism": "CMV-specific T-cell responses used as immune function reference.", "protein": "CMV glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Acute myeloblastic leukemia", "glycan_involvement": "HLA-DR is a glycoprotein; glycosylation affects stability and antigen presentation.", "mechanism": "Low/negative HLA-DR expression on monocytes may indicate presence of myeloid-derived suppressor cells (MDSCs), associated with immune suppression.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "Myelodysplastic syndrome", "glycan_involvement": "Glycosylation modulates HLA-DR function.", "mechanism": "Altered HLA-DR expression on monocytes may reflect immune dysregulation post-transplant.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation patterns influence vaccine efficacy and immune response.", "mechanism": "Target of mRNA vaccine (BNT162b2) to elicit protective immunity.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8701505" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects HLA-DR surface expression and function.", "mechanism": "Low HLA-DR on monocytes may indicate impaired immune response to vaccination.", "protein": "HLA-DR", "protein_enriched": { "function": "A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting c", "gene_name": "HLA-DRB1", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P01911" }, "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts T-cell epitope presentation.", "mechanism": "T-cell response to spike glycoprotein used to assess vaccine-induced cellular immunity.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701505" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycoprotein is heavily glycosylated, affecting antigenicity and immune recognition.", "mechanism": "Target antigen for vaccine-induced antibody response; seropositivity correlates with protection from severe COVID-19.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "Haematological malignancy", "glycan_involvement": "Glycosylation of spike protein influences vaccine efficacy.", "mechanism": "Impaired antibody response to spike glycoprotein after vaccination in patients with haematological malignancy, especially during/after B cell depletion.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "Autoimmune diseases (rheumatological disease)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Reduced serological response to spike glycoprotein in patients post B cell depletion therapy.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "Haematological malignancy", "glycan_involvement": "CD20 is a glycoprotein; glycosylation may affect antibody binding.", "mechanism": "Targeted by anti-CD20 B cell depleting agents to treat malignancy.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "Autoimmune diseases (rheumatological disease)", "glycan_involvement": "Glycosylation may influence therapeutic antibody efficacy.", "mechanism": "Targeted by anti-CD20 agents to deplete B cells in autoimmune conditions.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Immunoglobulins are glycoproteins; glycosylation affects effector function.", "mechanism": "Serological response (anti-spike IgG/A/M) is a correlate of vaccine-induced protection.", "protein": "Immunoglobulin G/A/M (IgG/A/M)", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "medium", "disease": "Secondary immunodeficiency", "glycan_involvement": "Glycosylation may modulate CD20 function and antibody interaction.", "mechanism": "Long-term B cell depletion via anti-CD20 therapy can cause persistent immunodeficiency.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "causal", "source_pmcid": "PMC8701526" }, { "confidence": "medium", "disease": "Secondary immunodeficiency", "glycan_involvement": "Glycosylation impacts immunogenicity.", "mechanism": "Failure to mount anti-spike antibody response indicates secondary immunodeficiency post B cell depletion.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "medium", "disease": "Follicular lymphoma", "glycan_involvement": "Glycosylation may affect therapeutic targeting.", "mechanism": "Anti-CD20 therapy used in follicular lymphoma; associated with long-term immunodeficiency in some patients.", "protein": "CD20", "protein_enriched": { "function": "B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, ", "gene_name": "MS4A1", "glycan_count": 4, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G18647XP", "G63041LO", "G70441OD", "G90659AW" ], "uniprot_id": "P11836" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8701526" }, { "confidence": "medium", "disease": "Secondary immunodeficiency", "glycan_involvement": "Glycosylation status may influence antibody stability and function.", "mechanism": "Low or absent anti-spike IgG/A/M after vaccination signals immunodeficiency.", "protein": "Immunoglobulin G/A/M (IgG/A/M)", "relationship_type": "biomarker", "source_pmcid": "PMC8701526" }, { "confidence": "high", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-AQP4 antibodies are associated with NMOSD and mediate astrocyte damage.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "high", "disease": "Optic Neuritis", "glycan_involvement": "MOG is glycosylated; glycosylation influences immune recognition.", "mechanism": "Anti-MOG antibodies are found in some cases of optic neuritis and NMOSD.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "high", "disease": "Transverse Myelitis", "glycan_involvement": "Glycosylation may modulate AQP4 immunogenicity.", "mechanism": "Anti-AQP4 antibodies are associated with longitudinally extensive transverse myelitis.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "medium", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "MOG glycosylation affects antibody binding.", "mechanism": "Anti-MOG antibodies are present in a subset of NMOSD patients.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "low", "disease": "Optic Neuritis", "glycan_involvement": "HBsAg is glycosylated; glycan structures may mediate molecular mimicry.", "mechanism": "Possible cross-reactivity between HBsAg and myelin antigens may trigger demyelination.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal (speculative)", "source_pmcid": "PMC8750780" }, { "confidence": "low", "disease": "Neuromyelitis Optica Spectrum Disorder (NMOSD)", "glycan_involvement": "Glycosylation of HBsAg may influence immune cross-reactivity.", "mechanism": "Suggested cross-reactivity between HBsAg and myelin proteins may contribute to NMOSD.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal (speculative)", "source_pmcid": "PMC8750780" }, { "confidence": "medium", "disease": "Guillain-Barr\u00e9 Syndrome (GBS)", "glycan_involvement": "GD1b is a glycosphingolipid; glycan moiety is the antigenic target.", "mechanism": "Anti-GD1b antibodies found in GBS variant with myelitis.", "protein": "GD1b ganglioside", "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "medium", "disease": "COVID-19-associated demyelinating disorders", "glycan_involvement": "Glycosylation may affect AQP4 immunogenicity in viral-triggered autoimmunity.", "mechanism": "COVID-19 may trigger immune response leading to anti-AQP4 antibody production.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "medium", "disease": "COVID-19-associated optic neuritis", "glycan_involvement": "MOG glycosylation may modulate immune response post-infection.", "mechanism": "COVID-19 may induce anti-MOG antibodies causing optic neuritis.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC8750780" }, { "confidence": "low", "disease": "COVID-19-associated demyelinating disorders", "glycan_involvement": "HBsAg glycosylation may facilitate molecular mimicry.", "mechanism": "Chronic HBV infection may interact with COVID-19 to increase risk of demyelination via immune cross-reactivity.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "causal (speculative)", "source_pmcid": "PMC8750780" }, { "confidence": "high", "disease": "COVID-19-associated thrombosis", "glycan_involvement": "\u03b22-glycoprotein I is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are transiently increased in severe COVID-19 and associated with thrombotic events.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "high", "disease": "Arterial thromboembolism (ATE)", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Triple positivity for anti-\u03b22-glycoprotein I, anti-cardiolipin, and LAC is associated with increased risk of ATE in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8763422" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation status may influence pathogenicity.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are diagnostic for APS and are transiently elevated in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "COVID-19-associated thrombosis", "glycan_involvement": "Target proteins are glycosylated; glycosylation may affect immune response.", "mechanism": "Anti-cardiolipin antibodies are transiently increased in severe COVID-19 and associated with thrombotic events.", "protein": "Cardiolipin-binding proteins (via anti-cardiolipin antibodies)", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "COVID-19-associated thrombosis", "glycan_involvement": "Targets glycoproteins; glycosylation may influence antibody binding.", "mechanism": "LAC positivity is frequent in severe COVID-19 and correlates with thrombotic risk.", "protein": "Lupus anticoagulant (LAC, targets phospholipid-binding proteins)", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation may affect antigenicity.", "mechanism": "Anti-\u03b22-glycoprotein I antibodies are found in patients with pulmonary embolism in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Triple positivity including anti-\u03b22-glycoprotein I is associated with stroke in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "Myocardial infarction", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Triple positivity including anti-\u03b22-glycoprotein I is associated with MI in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "Limb ischemia", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Triple positivity including anti-\u03b22-glycoprotein I is associated with limb ischemia in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "medium", "disease": "Bowel ischemia", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Triple positivity including anti-\u03b22-glycoprotein I is associated with bowel ischemia in COVID-19.", "protein": "\u03b22-glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8763422" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "MOG is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Anti-MOG antibodies are used to exclude MOG-associated disease in ADEM diagnosis.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8772132" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may influence antibody binding.", "mechanism": "Anti-AQP4 antibodies are diagnostic for NMOSD, which must be excluded in ADEM.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC8772132" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "IgG glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG is used as immunomodulatory therapy in ADEM cases.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8772132" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Spike glycoprotein mediates viral entry and immune response.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8772132" }, { "confidence": "medium", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "Glycosylation may affect immunogenicity and cross-reactivity.", "mechanism": "Post-infectious immune response to SARS-CoV-2 may trigger ADEM.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal (indirect/post-infectious)", "source_pmcid": "PMC8772132" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "Glycosylation may influence antibody recognition.", "mechanism": "Anti-MOG antibodies help distinguish NMOSD from ADEM.", "protein": "Myelin oligodendrocyte glycoprotein", "protein_enriched": { "function": "Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosph", "gene_name": "Psap", "glycan_count": 25, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G49108TO", "G00406II", "G05724UK", "G06110VR", "G25637MV", "G31685JQ", "G39188ZX", "G48584BU", "G49874UX", "G64527OM", "G66538GV", "G70101JE", "G74724QE", "G80920RR", "G93180LE", "G94854LT", "G62765YT", "G14260UH", "G14669DU", "G41247ZX", "G51895WL", "G63628AV", "G11870QZ", "G15664MX", "G55383ZG" ], "uniprot_id": "Q61207" }, "relationship_type": "biomarker", "source_pmcid": "PMC8772132" }, { "confidence": "medium", "disease": "Autoimmune encephalitis", "glycan_involvement": "IgG glycosylation affects efficacy and anti-inflammatory properties.", "mechanism": "IVIG is used to treat autoimmune encephalitis, which overlaps with ADEM.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8772132" }, { "confidence": "high", "disease": "Increased mortality in COVID-19", "glycan_involvement": "Albumin is N-glycosylated; altered glycosylation may affect stability and function.", "mechanism": "Hypoalbuminemia is associated with increased mortality risk in hospitalized COVID-19 patients.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "high", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Glycosylation status may influence albumin half-life and detection.", "mechanism": "Hypoalbuminemia reflects impaired hepatic synthetic function in COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "AP is a glycoprotein; glycosylation affects its secretion and activity.", "mechanism": "Elevated AP indicates cholestatic or hepatocellular injury in COVID-19.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "medium", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "AST is glycosylated; glycan modifications may affect serum levels.", "mechanism": "Elevated AST reflects hepatocellular injury in COVID-19 patients.", "protein": "Aspartate Aminotransferase (AST)", "protein_enriched": { "function": "Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular N", "gene_name": "GOT2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P00505" }, "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Altered glycosylation may contribute to hypoalbuminemia.", "mechanism": "Low albumin is a marker of disease severity in COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates AP function and serum levels.", "mechanism": "Elevated AP is more frequent in COVID-19 patients than in other liver diseases.", "protein": "Alkaline Phosphatase", "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "low", "disease": "Liver dysfunction in COVID-19", "glycan_involvement": "Carrier proteins (e.g., albumin) are glycosylated, affecting bilirubin transport.", "mechanism": "Increased total bilirubin reflects impaired hepatic excretion in COVID-19.", "protein": "Total Bilirubin (carrier proteins)", "relationship_type": "biomarker", "source_pmcid": "PMC8804228" }, { "confidence": "high", "disease": "\u03b2-thalassemia", "glycan_involvement": "N-glycosylation required for stability and receptor binding.", "mechanism": "Monoferric N-terminal transferrin ameliorates anemia and improves erythropoiesis in \u03b2-thalassemic mice.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8812097" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Glycosylation required for ligand binding and cell surface expression.", "mechanism": "P-selectin mediates sickle RBC and leukocyte adhesion, promoting vaso-occlusion; inhibition reduces VOE/VOC.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8812097" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Targets glycosylated P-selectin.", "mechanism": "Anti-P-selectin monoclonal antibody reduces frequency of vaso-occlusive crises by blocking P-selectin.", "protein": "Crizanlizumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8812097" }, { "confidence": "high", "disease": "Sickle cell disease (SCD)", "glycan_involvement": "Targets glycosylated P-selectin.", "mechanism": "Monoclonal antibody inhibits P-selectin-mediated cell adhesion, reducing risk of vaso-occlusion.", "protein": "Inclacumab", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "Alpha-thalassemia", "glycan_involvement": "Glycosylation critical for vWF multimerization and function.", "mechanism": "vWF release and deposition observed in severe alpha-thalassemia mouse model, associated with vaso-occlusive events.", "protein": "von Willebrand factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "Secreted glycoprotein; glycosylation may affect stability.", "mechanism": "ERFE levels reduced by iron restriction therapy, correlating with improved erythropoiesis.", "protein": "Erythroferrone (ERFE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Mediates iron uptake; interaction with transferrin variants modulates erythropoiesis.", "protein": "Transferrin receptor 1 (TFR1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "N-glycosylation required for receptor function.", "mechanism": "Modulates hepcidin expression and erythropoiesis in response to transferrin-bound iron.", "protein": "Transferrin receptor 2 (TFR2)", "protein_enriched": { "function": "Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation", "gene_name": "TFR2", "glycan_count": 0, "glycosylation_sites_count": 4, "glytoucan_ids": [], "uniprot_id": "Q9UP52" }, "relationship_type": "regulatory", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "N-glycosylation required for surface expression.", "mechanism": "Used as a marker for erythroid precursors and ineffective erythropoiesis in flow cytometry.", "protein": "CD71 (Transferrin receptor)", "protein_enriched": { "function": "Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (By similarity). Endosomal acidification leads to iron release. The ", "gene_name": "Tfrc", "glycan_count": 7, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G77547TA", "G05724UK", "G06110VR", "G72747WU", "G74724QE", "G47246VB", "G49108TO" ], "uniprot_id": "Q62351" }, "relationship_type": "biomarker", "source_pmcid": "PMC8812097" }, { "confidence": "medium", "disease": "\u03b2-thalassemia", "glycan_involvement": "Glycosylation required for antigenicity.", "mechanism": "Erythroid-specific glycoprotein antigen used to assess erythropoiesis in mouse models.", "protein": "TER119", "relationship_type": "biomarker", "source_pmcid": "PMC8812097" }, { "confidence": "high", "disease": "Pancreatic cancer", "glycan_involvement": "Effects are amplified when MUC6 is glycosylated with terminal \u03b11,4-linked N-acetylglucosamine (\u03b1GlcNAc).", "mechanism": "Ectopic expression of MUC6 reduces cell proliferation, motility, and invasiveness in pancreatic cancer cells.", "protein": "MUC6", "relationship_type": "protective", "source_pmcid": "PMC8819340" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Glycosylation status (presence of \u03b1GlcNAc) is relevant to biomarker potential.", "mechanism": "Higher MUC6 mRNA expression is associated with favorable prognosis in pancreatic cancer.", "protein": "MUC6", "relationship_type": "biomarker", "source_pmcid": "PMC8819340" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "A4GNT catalyzes the addition of \u03b11,4-linked GlcNAc to MUC6.", "mechanism": "Higher A4GNT mRNA expression correlates with favorable prognosis in pancreatic cancer.", "protein": "A4GNT (\u03b11,4-N-acetylglucosaminyltransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC8819340" }, { "confidence": "medium", "disease": "Pancreatic cancer", "glycan_involvement": "Directly responsible for \u03b11,4-linked GlcNAc addition to MUC6.", "mechanism": "Restoring or enhancing A4GNT activity may suppress malignancy via MUC6 glycosylation.", "protein": "A4GNT (\u03b11,4-N-acetylglucosaminyltransferase)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8819340" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding", "mechanism": "Mediates viral entry into host cells via ACE2 binding", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects receptor conformation and viral binding", "mechanism": "Serves as entry receptor for SARS-CoV-2 via S protein binding", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "Diarrhea", "glycan_involvement": "O-glycosylation critical for mucin function and barrier properties", "mechanism": "Forms protective mucus barrier in gut; altered during infection and dysbiosis", "protein": "Mucin", "relationship_type": "protective", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates antibody effector function", "mechanism": "Neutralize virus and modulate immune response", "protein": "Immunoglobulins (Igs)", "relationship_type": "protective", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation required for proper folding and cell surface expression", "mechanism": "Recognizes microbial components; upregulated in dysbiosis and COVID-19, promoting cytokine release", "protein": "TLR4", "protein_enriched": { "function": "Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstrea", "gene_name": "TLR4", "glycan_count": 1, "glycosylation_sites_count": 10, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00206" }, "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "Systemic inflammation", "glycan_involvement": "Glycosylation required for function", "mechanism": "Mediates inflammatory signaling in response to microbial products; upregulated in dysbiosis", "protein": "TLR2", "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "N-glycosylation affects secretion and stability", "mechanism": "Elevated in cytokine storm during severe COVID-19", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker", "source_pmcid": "PMC8825305" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates secretion and activity", "mechanism": "Major pro-inflammatory cytokine in COVID-19 cytokine storm", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "Gut dysbiosis", "glycan_involvement": "N-glycosylation modulates ACE2 localization and function", "mechanism": "ACE2 expression in gut epithelia mediates viral entry, leading to dysbiosis", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "medium", "disease": "Gut dysbiosis", "glycan_involvement": "Glycosylation shields S protein from immune detection in gut", "mechanism": "Viral infection of gut epithelia via S protein-ACE2 interaction disrupts microbiota", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8825305" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "HA is heavily glycosylated; glycosylation modulates antigenicity and immune recognition.", "mechanism": "Induction of neutralizing antibodies against HA prevents viral entry.", "protein": "Hemagglutinin (HA)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "Measles", "glycan_involvement": "Glycosylation affects receptor binding and immunogenicity.", "mechanism": "Antibodies to hemagglutinin block viral binding to host cells.", "protein": "Measles Hemagglutinin", "protein_enriched": { "function": "Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection. Unlike the other paramyxovirus attachment proteins, lacks both neuraminidase and hemaggluti", "gene_name": "G", "glycan_count": 0, "glycosylation_sites_count": 13, "glytoucan_ids": [], "uniprot_id": "P69351" }, "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "medium", "disease": "Mumps", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "Antibodies to surface glycoproteins neutralize virus.", "protein": "Mumps Virus Surface Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "medium", "disease": "Rubella", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Antibodies to glycoproteins prevent infection.", "protein": "Rubella Virus Surface Glycoproteins", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "Varicella (Chickenpox) / Herpes Zoster (Shingles)", "glycan_involvement": "gE is glycosylated, affecting immunogenicity.", "mechanism": "gE is the main antigen in subunit vaccine; induces strong antibody and T cell responses.", "protein": "Varicella-Zoster Virus Glycoprotein E (gE)", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike is extensively glycosylated; glycans shield epitopes and modulate immune response.", "mechanism": "Spike-specific antibodies block viral entry via ACE2.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "HBsAg is glycosylated, influencing secretion and immunogenicity.", "mechanism": "HBsAg induces neutralizing antibodies preventing infection.", "protein": "Hepatitis B Surface Antigen (HBsAg)", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "Human Papillomavirus-associated cancers", "glycan_involvement": "L1 is glycosylated in some expression systems, affecting assembly and immunogenicity.", "mechanism": "L1 forms virus-like particles that induce neutralizing antibodies.", "protein": "HPV L1 Major Capsid Protein", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "medium", "disease": "Rotavirus Gastroenteritis", "glycan_involvement": "VP7 is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "VP7-specific antibodies neutralize virus.", "protein": "Rotavirus VP7", "protein_enriched": { "function": "Accumulates harmlessly in the cytoplasmic membrane until it reaches a critical concentration that triggers the formation of micron-scale pores (holes) causing host cell membrane disruption and endolys", "gene_name": "14", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P11188" }, "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "medium", "disease": "Rotavirus Gastroenteritis", "glycan_involvement": "VP4 is glycosylated; glycosylation modulates host interaction.", "mechanism": "VP4-specific antibodies block viral attachment.", "protein": "Rotavirus VP4", "relationship_type": "protective", "source_pmcid": "PMC8830773" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity and immune recognition.", "mechanism": "MOG-IgG is used to distinguish MS from MOG-associated disorders; negative in these MS cases.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC8831192" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is glycosylated; glycosylation modulates antibody binding.", "mechanism": "AQP4-IgG is a diagnostic marker for NMOSD; negative in these MS cases.", "protein": "Aquaporin-4 (AQP4)", "protein_enriched": { "function": "Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport an", "gene_name": "AQP4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P55087" }, "relationship_type": "biomarker", "source_pmcid": "PMC8831192" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "IgG glycosylation modulates immune effector functions and autoimmunity.", "mechanism": "Elevated IgG index and oligoclonal bands in CSF are diagnostic for MS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8831192" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation affects IgG clearance and function.", "mechanism": "Plasma exchange removes pathogenic IgG in acute MS exacerbations.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8831192" }, { "confidence": "medium", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation influences MOG immunogenicity.", "mechanism": "Autoimmunity against MOG can cause demyelination, though not detected in these cases.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "causal", "source_pmcid": "PMC8831192" }, { "confidence": "high", "disease": "Multiple sclerosis (MS)", "glycan_involvement": "Glycosylation patterns may affect oligoclonal band formation.", "mechanism": "Oligoclonal bands in CSF indicate intrathecal IgG synthesis, a hallmark of MS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8831192" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "B2GPI is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "Autoantibodies against B2GPI are central to APS pathogenesis, promoting thrombosis and immune activation.", "protein": "\u03b22-Glycoprotein I (B2GPI)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8832411" }, { "confidence": "high", "disease": "Chorea/Choreo-athetosis", "glycan_involvement": "Glycosylation may modulate B2GPI structure and immune recognition.", "mechanism": "Anti-B2GPI antibodies (including IgA) are strongly associated with neurological manifestations such as chorea.", "protein": "\u03b22-Glycoprotein I (B2GPI)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Prothrombin is glycosylated; glycan structures may influence antibody binding.", "mechanism": "IgG antibodies against prothrombin (aPT) correlate with APS, especially CNS involvement.", "protein": "Prothrombin", "protein_enriched": { "function": "Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis,", "gene_name": "F2", "glycan_count": 100, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02886BB", "G04854VP", "G06356OH", "G08918WF", "G10486CT", "G12793SR", "G14972EH", "G20706XG", "G22572EH", "G23505EP", "G26330YA", "G27058EU", "G27126ED", "G28681TP", "G31852PQ", "G38663NM", "G40834TG", "G43223CG", "G45395BF", "G45504EY", "G48414YA", "G50045TK", "G51413EV", "G56284ZY", "G56784JY", "G57317CE", "G57776ZU", "G59626AS", "G62765YT", "G70619PT", "G72787SB", "G75850OP", "G80920RR", "G84467IZ", "G87389XI", "G90659AW", "G91365ZQ", "G92551JA", "G94470IW", "G95865ZB", "G05933EN", "G06247RL", "G08110WX", "G08293MJ", "G08578KJ", "G15169WU", "G22310AV", "G24084IV", "G26915XM", "G27947YN", "G31916IQ", "G37399XV", "G41071NU", "G42358LZ", "G47518TP", "G47737VJ", "G49906RN", "G52527GH", "G61256FT", "G63980BQ", "G64275UO", "G72291OX", "G77669RF", "G78502KD", "G82463GQ", "G84452RH", "G88374WZ", "G94917XT", "G43417UB", "G57321FI", "G37881RL", "G02030ZB", "G08394CG", "G10846ZT", "G11629QQ", "G22140GZ", "G22768VO", "G24954UD", "G37868ZX", "G40574BA", "G46902YN", "G57776ZS", "G57888GL", "G60923RB", "G66163OV", "G70232NH", "G70375MX", "G70888PK", "G72197KC", "G72398FA", "G72747WU", "G75983OB", "G78790NZ", "G85269DF", "G86880BF", "G88421PE", "G90093AU", "G99668VU" ], "uniprot_id": "P00734" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Annexin V is a glycoprotein; glycosylation may affect immune interactions.", "mechanism": "IgG antibodies against annexin V are associated with APS-CNS manifestations.", "protein": "Annexin V", "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Targeted via glycoprotein complexes; glycosylation may affect immune complex formation.", "mechanism": "Anticardiolipin antibodies (ACA) are diagnostic and pathogenic in APS, promoting thrombosis.", "protein": "Cardiolipin (via anticardiolipin antibodies)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Prothrombin glycosylation may affect complex formation and antigenicity.", "mechanism": "Antibodies against this complex are non-criteria aPLs, increasingly recognized in APS diagnosis.", "protein": "Phosphatidylserine/prothrombin complex", "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Interaction may involve glycoprotein complexes.", "mechanism": "IgG antibodies against phosphatidylglycerol correlate with APS-CNS manifestations.", "protein": "Phosphatidylglycerol", "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Likely involves glycoprotein-phospholipid complexes.", "mechanism": "IgG antibodies against phosphatidylinositol are associated with APS-CNS involvement.", "protein": "Phosphatidylinositol", "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "medium", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "C4 is a glycoprotein; glycosylation is essential for function.", "mechanism": "Low complement C4 is observed in APS, reflecting immune activation.", "protein": "Complement C4", "protein_enriched": { "function": "Probable neurotoxin", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C2S8" }, "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "low", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Vimentin is glycosylated; glycan structures may affect antigenicity.", "mechanism": "Anti-vimentin antibodies are non-criteria aPLs, under investigation for APS relevance.", "protein": "Vimentin", "protein_enriched": { "function": "Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either", "gene_name": "VIM", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO", "G41247ZX", "G70994MS", "G65021EF" ], "uniprot_id": "P08670" }, "relationship_type": "biomarker", "source_pmcid": "PMC8832411" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I affects its antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I are diagnostic for APS and contribute to thrombosis.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8832427" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may modulate antigenicity.", "mechanism": "Presence of anticardiolipin antibodies is used to diagnose APS and assess thrombosis risk.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC8832427" }, { "confidence": "medium", "disease": "Beh\u00e7et\u2019s Disease", "glycan_involvement": "Glycosylation state may influence immune recognition in BD.", "mechanism": "Autoantibodies to beta-2 glycoprotein I are observed in BD, especially with vascular involvement.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8832427" }, { "confidence": "high", "disease": "Beh\u00e7et\u2019s Disease", "glycan_involvement": "HLA-B51 is a glycoprotein; glycosylation affects peptide presentation and immune response.", "mechanism": "Strong genetic association; HLA-B51 increases risk for BD.", "protein": "HLA-B51", "relationship_type": "causal", "source_pmcid": "PMC8832427" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may affect antigenicity.", "mechanism": "Presence of lupus anticoagulant is diagnostic for APS and increases thrombosis risk.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC8832427" }, { "confidence": "medium", "disease": "Deep Vein Thrombosis", "glycan_involvement": "Glycosylation modulates immune response and thrombogenicity.", "mechanism": "Autoantibodies to beta-2 glycoprotein I promote thrombosis in APS, leading to DVT.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8832427" }, { "confidence": "medium", "disease": "Pulmonary Embolism", "glycan_involvement": "Glycosylation influences antigenicity and pathogenicity.", "mechanism": "Autoantibodies to beta-2 glycoprotein I contribute to thrombotic events such as PE in APS.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8832427" }, { "confidence": "medium", "disease": "Beh\u00e7et\u2019s Disease", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may modulate immune response.", "mechanism": "Anticardiolipin antibodies are sometimes present in BD, especially with vascular involvement.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC8832427" }, { "confidence": "low", "disease": "Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "HLA-B51 may modify risk of APS in BD patients.", "protein": "HLA-B51", "relationship_type": "risk modifier", "source_pmcid": "PMC8832427" }, { "confidence": "low", "disease": "Beh\u00e7et\u2019s Disease", "glycan_involvement": "Glycosylation may affect therapeutic antibody binding.", "mechanism": "Potential target for immunomodulation in BD with APS overlap.", "protein": "Beta-2 glycoprotein I", "relationship_type": "therapeutic target", "source_pmcid": "PMC8832427" }, { "confidence": "high", "disease": "Catastrophic Antiphospholipid Syndrome (cAPS)", "glycan_involvement": "Glycosylation of beta-2 glycoprotein 1 affects its antigenicity and antibody binding.", "mechanism": "Anti-beta-2 glycoprotein 1 antibodies are diagnostic for cAPS and mediate thrombosis.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC8832446" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Presence of anti-beta-2 glycoprotein 1 antibodies is a diagnostic criterion for APS.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC8832446" }, { "confidence": "high", "disease": "Catastrophic Antiphospholipid Syndrome (cAPS)", "glycan_involvement": "Fc glycosylation of IgG influences effector function and pathogenicity.", "mechanism": "High-titre IgG anticardiolipin antibodies are diagnostic for cAPS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8832446" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation status can modulate antibody activity.", "mechanism": "IgG anticardiolipin antibodies are a diagnostic marker for APS.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8832446" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Glycosylation of ab2GPI affects antibody recognition and pathogenicity", "mechanism": "ab2GPI is the main antigenic target for antiphospholipid antibodies in APS diagnosis", "protein": "Beta-2 Glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8832454" }, { "confidence": "high", "disease": "Obstetric Antiphospholipid Syndrome", "glycan_involvement": "Glycosylation modulates antigenicity and immune complex formation", "mechanism": "Persistent anti-beta-2 glycoprotein I antibodies are diagnostic for obstetric APS", "protein": "Beta-2 Glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8832454" }, { "confidence": "medium", "disease": "Pre-eclampsia", "glycan_involvement": "Altered glycosylation may enhance pathogenic antibody binding", "mechanism": "Anti-beta-2 glycoprotein I antibodies are associated with increased risk of pre-eclampsia in APS", "protein": "Beta-2 Glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8832454" }, { "confidence": "medium", "disease": "Pregnancy Loss/Miscarriage", "glycan_involvement": "Glycosylation state influences immune complex formation", "mechanism": "Anti-beta-2 glycoprotein I antibodies contribute to placental dysfunction and miscarriage", "protein": "Beta-2 Glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8832454" }, { "confidence": "low", "disease": "Placental Abruption", "glycan_involvement": "Glycosylation may affect pathogenicity", "mechanism": "Non-criteria APS manifestations include placental abruption linked to anti-beta-2 glycoprotein I antibodies", "protein": "Beta-2 Glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC8832454" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Antigenic complex involves glycoprotein (ab2GPI) binding", "mechanism": "Anti-cardiolipin antibodies are diagnostic for APS", "protein": "Cardiolipin (as antigen for aCL antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC8832454" }, { "confidence": "high", "disease": "Antiphospholipid Syndrome (APS)", "glycan_involvement": "Targets glycoprotein-phospholipid complexes", "mechanism": "LAC is a diagnostic antibody for APS", "protein": "Lupus Anticoagulant (LAC)", "relationship_type": "biomarker", "source_pmcid": "PMC8832454" }, { "confidence": "medium", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation modulates immune recognition", "mechanism": "Anti-beta-2 glycoprotein I antibodies are frequently found in SLE patients with APS", "protein": "Beta-2 Glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC8832454" }, { "confidence": "high", "disease": "Nipah virus infection (encephalitis and respiratory illness)", "glycan_involvement": "Glycosylation affects protein folding, antigenicity, and immune recognition.", "mechanism": "Mediates viral attachment to host cells, enabling infection.", "protein": "Nipah virus attachment G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8833029" }, { "confidence": "high", "disease": "Nipah virus infection (encephalitis and respiratory illness)", "glycan_involvement": "Glycan structures influence neutralization epitopes and immune response.", "mechanism": "Targeted by monoclonal antibodies and vaccine candidates.", "protein": "Nipah virus attachment G glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8833029" }, { "confidence": "high", "disease": "Hendra virus infection", "glycan_involvement": "Glycosylation affects protein structure and immune evasion.", "mechanism": "Mediates viral attachment to host cells, enabling infection.", "protein": "Hendra virus attachment G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8833029" }, { "confidence": "high", "disease": "Hendra virus infection", "glycan_involvement": "Glycosylation impacts immunogenicity and vaccine efficacy.", "mechanism": "Used as antigen in approved equine vaccine.", "protein": "Hendra virus attachment G glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8833029" }, { "confidence": "medium", "disease": "Nipah virus infection (encephalitis and respiratory illness)", "glycan_involvement": "Glycan modifications affect antigenicity.", "mechanism": "Key antigen for serological detection and immune monitoring.", "protein": "Nipah virus attachment G glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC8833029" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates spike conformational dynamics, enhancing receptor search and viral infectivity.", "mechanism": "Spike glycoprotein mediates viral entry by binding to host cell receptors, initiating infection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8833048" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans influence antibody accessibility and spike structure.", "mechanism": "Spike glycoprotein is targeted by therapeutic antibodies to block viral entry.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8833048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycan-glycan and glycan-lipid interactions amplify spike flexibility and search area.", "mechanism": "Flexible hinge regions in the glycosylated spike enhance conformational motions, increasing host cell receptor engagement.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8833048" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation at hinge regions modulates their dynamics and function.", "mechanism": "Hinge regions in the spike are potential targets for novel therapeutics.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8833048" }, { "confidence": "high", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "Ferritin is N-glycosylated, which may affect its stability and serum half-life.", "mechanism": "Elevated ferritin reflects hyperinflammation and iron sequestration during severe infection; induced by IL-6 and hepcidin.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "Cytokine storm syndrome", "glycan_involvement": "N-glycosylation may modulate ferritin's immune recognition.", "mechanism": "High ferritin is associated with cytokine storm and immune dysregulation in severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "Secondary hemophagocytic lymphohistiocytosis (sHLH)", "glycan_involvement": "N-glycosylation may influence ferritin's clearance.", "mechanism": "Markedly elevated ferritin is a diagnostic marker for sHLH, which can complicate severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "CRP N-glycosylation affects its solubility and immune function.", "mechanism": "CRP is elevated in severe cases, reflecting systemic inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "D-dimer fragments derive from N-glycosylated fibrinogen; glycosylation affects clot structure.", "mechanism": "Elevated D-dimer indicates hypercoagulability and risk of thrombotic complications.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "N-glycosylation is essential for P-selectin's cell adhesion function.", "mechanism": "Surface exposure of P-selectin on activated platelets promotes leukocyte recruitment and inflammation.", "protein": "Platelet P-selectin", "relationship_type": "causal", "source_pmcid": "PMC8857879" }, { "confidence": "medium", "disease": "COVID-19 (severe/critical)", "glycan_involvement": "N-glycosylation is required for E-selectin ligand binding.", "mechanism": "E-selectin mediates leukocyte adhesion and transmigration, contributing to lung injury.", "protein": "Platelet E-selectin", "relationship_type": "causal", "source_pmcid": "PMC8857879" }, { "confidence": "high", "disease": "Giardia duodenalis infection", "glycan_involvement": "Regiospecific changes in glycan composition (N-acetylglucosamine, sialic acid, fucose, mannose) on MUC2.", "mechanism": "Giardia infection disrupts MUC2 glycosylation, altering mucus barrier integrity.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC8859127" }, { "confidence": "high", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Decreased sialic acid and fucose in jejunum; increased mannose and sialic acid in colon.", "mechanism": "Altered glycosylation of MUC2 compromises mucus gel structure, increasing permeability.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC8859127" }, { "confidence": "medium", "disease": "Intestinal inflammation", "glycan_involvement": "Altered glycosyltransferase gene expression (Chst4, Fut2, St6GalNAc1, C2GnT1).", "mechanism": "Changes in mucin glycosylation patterns are associated with inflammation.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC8859127" }, { "confidence": "medium", "disease": "Dysbiosis", "glycan_involvement": "Changes in glycan structures provide different microbial binding sites.", "mechanism": "Altered mucin glycans affect microbial binding and nutrient availability, contributing to dysbiosis.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "causal", "source_pmcid": "PMC8859127" }, { "confidence": "medium", "disease": "Giardia duodenalis infection", "glycan_involvement": "Lectin staining reveals region-specific glycan changes.", "mechanism": "Altered glycosylation patterns of MUC2 can indicate Giardia infection.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC8859127" }, { "confidence": "low", "disease": "Intestinal barrier dysfunction", "glycan_involvement": "Targeting glycosyltransferase activity to normalize glycan composition.", "mechanism": "Restoring normal glycosylation of MUC2 may improve barrier function.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8859127" }, { "confidence": "high", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Heavily glycosylated; glycosylation shields GP from host immune recognition and is essential for function.", "mechanism": "Mediates viral entry into host cells by binding and fusion, initiating infection.", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8860457" }, { "confidence": "high", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Target of vaccines (DNA, adenovirus, VSV-based) and monoclonal antibodies; induces protective immunity.", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8860457" }, { "confidence": "medium", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation of GP1 modulates receptor binding and immune evasion.", "mechanism": "GP1 (produced by host cathepsin cleavage) binds NPC-1 in endosome, enabling viral fusion and entry.", "protein": "GP1", "relationship_type": "causal", "source_pmcid": "PMC8860457" }, { "confidence": "medium", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation influences antibody recognition.", "mechanism": "GP-specific antibodies indicate exposure or vaccine response.", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8860457" }, { "confidence": "medium", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation likely impacts immunogenicity.", "mechanism": "Used in multivalent vaccines to induce immunity against Sudan ebolavirus.", "protein": "SEBOV-GP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8860457" }, { "confidence": "medium", "disease": "Marburg virus disease", "glycan_involvement": "Glycosylation modulates immune response.", "mechanism": "Included in multivalent vaccines for cross-protection.", "protein": "Marburgvirus glycoprotein (MARV-GP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8860457" }, { "confidence": "low", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation likely affects antigenicity.", "mechanism": "Component of multivalent vaccines for broad ebolavirus protection.", "protein": "ICEBOV-GP", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8860457" }, { "confidence": "high", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation influences immune recognition and vaccine efficacy.", "mechanism": "Immunization with GP induces protective antibodies and T-cell responses.", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC8860457" }, { "confidence": "high", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "Glycosylation can mask epitopes, affecting antibody binding.", "mechanism": "Targeted by monoclonal antibody therapies (e.g., Zmapp).", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8860457" }, { "confidence": "high", "disease": "Ebolavirus disease (EVD)", "glycan_involvement": "N- and O-glycosylation critical for function and immune evasion.", "mechanism": "Glycoprotein mediates host cell entry and is essential for viral pathogenesis.", "protein": "Ebolavirus glycoprotein (GP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8860457" }, { "confidence": "medium", "disease": "Guillain-Barre syndrome (GBS)", "glycan_involvement": "Glycosylation of spike protein may enhance immunogenicity and molecular mimicry.", "mechanism": "Molecular mimicry between spike protein and myelin proteins may trigger autoimmune response leading to GBS.", "protein": "S glycoprotein (Spike protein) of SARS-CoV-2", "relationship_type": "causal", "source_pmcid": "PMC8864061" }, { "confidence": "medium", "disease": "Guillain-Barre syndrome (GBS)", "glycan_involvement": "Glycan structures on myelin proteins are targets for cross-reactive antibodies.", "mechanism": "Autoantibodies generated post-vaccination may cross-react with myelin glycoproteins, causing demyelination.", "protein": "Myelin protein (general, e.g., myelin-associated glycoprotein)", "relationship_type": "causal", "source_pmcid": "PMC8864061" }, { "confidence": "low", "disease": "Guillain-Barre syndrome (GBS)", "glycan_involvement": "Potential glycosylation of vector proteins may contribute to immune cross-reactivity.", "mechanism": "Adenoviral vector proteins may share glycan epitopes with host neural antigens, promoting molecular mimicry.", "protein": "Adenoviral vector proteins", "relationship_type": "causal", "source_pmcid": "PMC8864061" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "Elevated CRP indicates systemic inflammation and predicts ICU admission and mortality.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Ferritin glycosylation modulates its secretion and immune interactions.", "mechanism": "High ferritin reflects hyperinflammation and correlates with severe disease and ICU admission.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "AST glycosylation may influence enzyme stability and clearance.", "mechanism": "Elevated AST is associated with tissue damage and predicts ICU admission and mortality.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of CD markers regulates lymphocyte trafficking and immune response.", "mechanism": "Lymphopenia (low lymphocyte count) predicts severe COVID-19 outcomes.", "protein": "Lymphocyte surface glycoproteins (CD markers)", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "Altered glycosylation in CVD may enhance CRP pro-inflammatory activity.", "mechanism": "CRP is elevated in CVD and predicts worse outcomes in COVID-19 patients with CVD.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Diabetes alters CRP glycosylation, affecting its inflammatory properties.", "mechanism": "CRP is elevated in diabetes and predicts ICU admission in COVID-19 patients with diabetes.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Cancer-associated glycosylation changes may affect ferritin immunogenicity.", "mechanism": "High ferritin is common in cancer and predicts mortality in COVID-19 patients with cancer.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Obesity may alter AST glycosylation, impacting metabolic clearance.", "mechanism": "Obesity increases risk of elevated AST and severe COVID-19 outcomes.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "low", "disease": "Cancer", "glycan_involvement": "Cancer alters glycosylation of lymphocyte glycoproteins, impairing immune function.", "mechanism": "Cancer patients often have lymphopenia, worsening COVID-19 prognosis.", "protein": "Lymphocyte surface glycoproteins (CD markers)", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Obesity modifies CRP glycosylation, enhancing inflammatory signaling.", "mechanism": "Obesity is associated with higher CRP, increasing risk of severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8884751" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells, initiating infection.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects S protein binding affinity.", "mechanism": "Acts as the host receptor for S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8901424" }, { "confidence": "high", "disease": "Severe acute respiratory syndrome (SARS)", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor interaction.", "mechanism": "SARS-CoV S protein binds ACE2, similar to SARS-CoV-2.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "high", "disease": "Middle East respiratory syndrome (MERS)", "glycan_involvement": "Glycosylation affects receptor binding and immune recognition.", "mechanism": "MERS-CoV S protein binds DPP4 for host entry.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "medium", "disease": "Middle East respiratory syndrome (MERS)", "glycan_involvement": "Glycosylation of DPP4 influences viral binding.", "mechanism": "Host receptor for MERS-CoV S protein.", "protein": "DPP4", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8901424" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential O-glycosylation may affect immune recognition.", "mechanism": "Involved in viral replication and assembly; detected in infected tissues.", "protein": "Nucleocapsid protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901424" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates immune evasion, contributing to pathogenesis.", "mechanism": "Viral entry via S protein triggers immune response leading to ARDS.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "medium", "disease": "Atypical pneumonia", "glycan_involvement": "Glycosylation shields S protein from immune detection.", "mechanism": "Viral infection of lung epithelium via S protein causes pneumonia.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans near RBD modulate ACE2 binding and antibody accessibility.", "mechanism": "Contains receptor-binding domain (RBD) for ACE2 interaction.", "protein": "S1 subunit of S protein", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:32155444, PubMed:33607086). When S2/S2' h", "gene_name": "S", "glycan_count": 379, "glycosylation_sites_count": 26, "glytoucan_ids": [ "G00406II", "G01650EU", "G02402FF", "G02815KT", "G03382KH", "G03574QJ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09528DL", "G10256JP", "G10339FR", "G10486CT", "G10773YW", "G11460AB", "G11870QZ", "G12313PD", "G12580WI", "G12849CJ", "G14669DU", "G14994KB", "G15486FH", "G16407EV", "G20425TQ", "G20956ZV", "G21726WW", "G22768VO", "G23294PN", "G23432EQ", "G23453IV", "G23863VK", "G24954UD", "G25637MV", "G25987BV", "G27622TD", "G28541PG", "G28681TP", "G28997IA", "G29880MM", "G31596VW", "G31685JQ", "G31852PQ", "G31916IQ", "G31936TA", "G32104JU", "G33609NS", "G34617SM", "G35029YA", "G37399XV", "G39188ZX", "G39446WN", "G39943KJ", "G41247ZX", "G43638QT", "G44211QA", "G44953PJ", "G45504EY", "G46687AB", "G49874UX", "G49955PK", "G50045TK", "G50073PQ", "G50757KG", "G51210WZ", "G51287LK", "G53434XO", "G54600FO", "G55382TU", "G55383ZG", "G57317CE", "G57776ZU", "G59626AS", "G59937CP", "G60145BJ", "G62765YT", "G63628AV", "G64162JC", "G64394MX", "G64527OM", "G66538GV", "G66676MI", "G67324HN", "G68318VE", "G69364JQ", "G70101JE", "G70375MX", "G72667IM", "G72735IY", "G72787SB", "G72791KH", "G74430RZ", "G74724QE", "G78790NZ", "G80475RE", "G80735OA", "G80920RR", "G80966KZ", "G81263BG", "G81295CK", "G82020ZR", "G82119TF", "G82364UA", "G83555HU", "G83633GK", "G84452RH", "G84820NF", "G85740DB", "G86752LQ", "G88725PI", "G89319AW", "G90093AU", "G91636VS", "G92050GC", "G92597CK", "G93579XB", "G94854LT", "G95368PR", "G95865ZB", "G00031MO", "G29931IJ", "G57321FI", "G00912UN", "G02030ZB", "G02315DX", "G02886BB", "G03717EM", "G04672QB", "G09197ZW", "G11629QQ", "G11911BT", "G12793SR", "G14260UH", "G15038BD", "G19517GM", "G20698EO", "G22310AV", "G23505EP", "G24835MQ", "G25079LO", "G25418HZ", "G27947YN", "G29651HS", "G32926LW", "G36670VW", "G37818NZ", "G37881RL", "G39619TI", "G40926MX", "G41126SR", "G41882MT", "G43669FQ", "G43734MM", "G43769HG", "G44753VC", "G45883VE", "G46902YN", "G48414YA", "G48584BU", "G49906RN", "G50120TH", "G51640FO", "G52527GH", "G54417MJ", "G56610MH", "G57888GL", "G59536GA", "G61613II", "G65092SV", "G65184UU", "G66760KM", "G70822IO", "G72291OX", "G72790NZ", "G72797UR", "G73686WG", "G79568CQ", "G82463GQ", "G82830MN", "G83646BJ", "G85144OK", "G85282JO", "G85291BI", "G86182NS", "G87015RU", "G88374WZ", "G89098OM", "G93656SY", "G98596OT", "G99966GV", "G91473PK", "G49739MP", "G67367OT", "G21976AG", "G41044JW", "G54740VA", "G69834CE", "G94917XT", "G95678HJ", "G05850WN", "G05926FW", "G06247RL", "G06656BE", "G06853GH", "G08146BT", "G08578KJ", "G10374FO", "G11115RO", "G12341GU", "G13728QT", "G14368ET", "G15127JD", "G15169WU", "G16175ZV", "G17650MH", "G19379ID", "G22140GZ", "G24481HY", "G25216KM", "G26403SG", "G27033WF", "G27126ED", "G28622IK", "G30630UO", "G31153XO", "G31986NC", "G33556XM", "G34029GR", "G37412TK", "G37868ZX", "G39471UU", "G42358LZ", "G43157UW", "G45495MK", "G46982GD", "G47012YE", "G49018RC", "G51572MS", "G52589SM", "G53315IV", "G55216FT", "G55868RH", "G57818FI", "G59639BE", "G60033FS", "G60070LT", "G61302NC", "G61627IG", "G61937QU", "G62165AG", "G62595EF", "G62792OG", "G62894KT", "G67506FN", "G68164MW", "G68209WQ", "G70418MS", "G73430PD", "G75568BH", "G75607BQ", "G80223IX", "G81198YO", "G83141DC", "G83295QG", "G83460ZZ", "G85228QD", "G85987RP", "G87208AT", "G89009DQ", "G90734RJ", "G90885MZ", "G93999ON", "G95484XN", "G95835XS", "G97876DH", "G98611JV", "G99679NM", "G07799LX", "G13716SG", "G22625SJ", "G25451PN", "G34852SB", "G46241DR", "G51413EV", "G56284ZY", "G59540CB", "G64615IX", "G69107AL", "G70087PV", "G82592ZH", "G87051GH", "G93526NJ", "G95977AE", "G96430BV", "G31544HA", "G83213GG", "G03596YS", "G04784US", "G20312EM", "G44215PV", "G47737VJ", "G60923RB", "G61855PQ", "G75983OB", "G86795LJ", "G31028YV", "G37659EV", "G40206WX", "G51637RO", "G59334JE", "G66362RJ", "G78502KD", "G08110WX", "G12872WY", "G14926RK", "G16462LS", "G20606AK", "G39595FH", "G49084LP", "G54612UD", "G60743GT", "G63543FL", "G63976XX", "G90789YQ", "G00033MO", "G17015OC", "G17041QN", "G18946TX", "G19399OS", "G23729WG", "G29068FM", "G32550BI", "G43417UB", "G60038ZA", "G60554YG", "G68008QO", "G74722FL", "G81006GJ", "G98535LH", "G03127AL", "G05049IC", "G14889BN", "G19603RR", "G25379SA", "G27102CT", "G29501UT", "G32332VU", "G42962KI", "G56903ZB", "G62461SM", "G66163OV", "G66933CM", "G68698AP", "G70894RY", "G71146HJ", "G76417NN", "G83014KM", "G90448RI", "G93180LE", "G93683YO", "G02628JF", "G96416FQ", "G96577RX", "G03027LH", "G08011QI", "G22040QI", "G26759AS", "G76613WN", "G21643DJ", "G30799SW", "G58802FE", "G60177UT", "G66766XF", "G86408JD", "G50427EO", "G66088HZ", "G81128KB", "G29255IL", "G47518TP" ], "uniprot_id": "P0DTC2" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8901424" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect fusion efficiency and immune evasion.", "mechanism": "Mediates membrane fusion after receptor binding.", "protein": "S2 subunit of S protein", "relationship_type": "causal", "source_pmcid": "PMC8901424" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates antigenicity and immune evasion.", "mechanism": "Surface glycoprotein mediates viral entry and is targeted for detection.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and immune recognition.", "mechanism": "Surface glycoprotein involved in viral release; detected by biosensors.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation shields epitopes from immune detection.", "mechanism": "Envelope glycoprotein essential for viral fusion; used for disease progression monitoring.", "protein": "gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense glycosylation forms 'glycan shield' for immune evasion.", "mechanism": "Envelope glycoprotein mediates host cell attachment; detected in diagnostics.", "protein": "gp120", "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Glycosylation required for secretion and immune modulation.", "mechanism": "Secreted glycoprotein present in patient serum; early diagnostic marker.", "protein": "Nonstructural protein 1 (NS1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "Zika virus disease", "glycan_involvement": "Glycosylation affects antigenicity and detection specificity.", "mechanism": "Secreted glycoprotein distinguishes ZIKV from other flaviviruses; used in biosensor detection.", "protein": "Nonstructural protein 1 (ns1)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "medium", "disease": "Zika virus disease", "glycan_involvement": "Glycosylation modulates immune recognition.", "mechanism": "Domain III of envelope glycoprotein is antigenic and used for specific detection.", "protein": "Envelope protein domain III (EDIII)", "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "Glycosylation required for secretion and immunogenicity.", "mechanism": "Envelope glycoprotein detected in serum as marker of acute infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "Glycosylation may affect membrane localization.", "mechanism": "Transmembrane glycoprotein targeted for subtype-specific detection.", "protein": "Matrix protein 2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "medium", "disease": "Enterovirus 71 infection", "glycan_involvement": "Glycosylation influences antigenicity.", "mechanism": "Capsid glycoprotein used for optical biosensor detection.", "protein": "Major capsid protein VP1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8901426" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP glycosylation affects its stability and immune recognition.", "mechanism": "CRP levels increase as part of the acute phase response to inflammation in severe COVID-19.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "Albumin glycosylation modulates its half-life and function.", "mechanism": "Decreased serum albumin indicates impaired liver synthetic function in severe COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "Hypothyroidism", "glycan_involvement": "TSH is a heavily glycosylated hormone; glycosylation is essential for its bioactivity.", "mechanism": "Altered TSH levels reflect thyroid dysfunction in COVID-19 patients.", "protein": "Thyroid stimulating hormone (TSH)", "protein_enriched": { "function": "Indispensable for the control of thyroid structure and metabolism", "gene_name": "TSHB", "glycan_count": 7, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G08185DV", "G14358WN", "G16122GW", "G24954RW", "G38217AM", "G41708PN", "G77198CF" ], "uniprot_id": "P01222" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "Thyroxine precursor glycosylation affects hormone release.", "mechanism": "Elevated or suppressed free T4 levels indicate thyroid dysfunction during COVID-19.", "protein": "Free T4 (Thyroxine)", "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer is a glycosylated fibrin fragment; glycosylation affects clearance.", "mechanism": "Elevated D-dimer reflects coagulopathy and increased risk of thrombosis in severe COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "ALT glycosylation may affect enzyme stability.", "mechanism": "Elevated ALT indicates liver injury in COVID-19 patients.", "protein": "Alanine aminotransferase (ALT)", "protein_enriched": { "function": "Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "Hepatic dysfunction", "glycan_involvement": "AST glycosylation may influence enzyme activity.", "mechanism": "Elevated AST is associated with liver and multi-organ injury in severe COVID-19.", "protein": "Aspartate aminotransferase (AST)", "protein_enriched": { "function": "Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system", "gene_name": "GOT1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P17174" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "Amylase glycosylation affects secretion and activity.", "mechanism": "Elevated amylase indicates pancreatic injury in COVID-19.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "medium", "disease": "Acute pancreatitis", "glycan_involvement": "Lipase glycosylation modulates enzyme function.", "mechanism": "Elevated lipase is a marker of pancreatic injury in COVID-19.", "protein": "Lipase", "protein_enriched": { "function": "Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:18702514, PubMed:19451396, PubMed:20083229, PubMed:21865348, PubMed:26494624). In neon", "gene_name": "PNLIPRP2", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P54317" }, "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Cell surface glycoproteins mediate immune cell interactions and response.", "mechanism": "Altered WBC counts and glycoprotein expression reflect immune dysregulation in COVID-19.", "protein": "White blood cell glycoproteins (general)", "relationship_type": "biomarker", "source_pmcid": "PMC8907905" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Spike protein mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "high", "disease": "Respiratory disorders", "glycan_involvement": "Glycosylation affects immune evasion and infectivity.", "mechanism": "Spike protein enables SARS-CoV-2 infection of respiratory tract cells.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence viral particle stability.", "mechanism": "M protein is essential for viral assembly and infectivity.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding and immune recognition.", "mechanism": "HE protein facilitates virus entry and spread.", "protein": "Hemagglutinin-esterase dimer (HE)", "protein_enriched": { "function": "Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection", "gene_name": "S", "glycan_count": 0, "glycosylation_sites_count": 30, "glytoucan_ids": [], "uniprot_id": "Q14EB0" }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation affects virion stability.", "mechanism": "E protein involved in virus assembly and pathogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates spike binding affinity.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2 spike protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "Cardiovascular disorders", "glycan_involvement": "Glycosylation may influence tissue tropism.", "mechanism": "Spike-mediated infection can affect heart tissue via ACE2 expression.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "Neurological disorders", "glycan_involvement": "Glycosylation may affect neuroinvasion.", "mechanism": "Spike protein interaction with ACE2 in neuronal cells may contribute to neurodegeneration.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Glycosylation may modulate immune response and metabolic impact.", "mechanism": "COVID-19 infection can exacerbate metabolic dysfunction via spike-ACE2 interaction.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "medium", "disease": "Black mold disease", "glycan_involvement": "Glycosylation may affect immune evasion and co-infection risk.", "mechanism": "COVID-19 infection increases susceptibility to secondary fungal infections.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8939627" }, { "confidence": "high", "disease": "Severe COVID-19 pneumonia", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function in immune signaling.", "mechanism": "CRP is induced by IL-6 during inflammation; elevated levels indicate severe systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation modulates CRP's interaction with immune cells.", "mechanism": "High CRP levels correlate with increased risk of death, reflecting severe inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "high", "disease": "Severe COVID-19 pneumonia", "glycan_involvement": "D-dimer is a glycopeptide; glycosylation may affect clearance and detection.", "mechanism": "Elevated D-dimer reflects coagulation activation and fibrinolysis, indicating severe disease.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation may influence D-dimer's half-life and immunogenicity.", "mechanism": "High D-dimer is associated with increased mortality due to coagulopathy.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "medium", "disease": "Severe COVID-19 pneumonia", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect secretion and immune recognition.", "mechanism": "Elevated ferritin indicates hyperinflammation and macrophage activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "medium", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation may modulate ferritin's immunomodulatory properties.", "mechanism": "High ferritin levels are linked to increased risk of death, reflecting cytokine storm.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "medium", "disease": "Respiratory bacterial co-infection", "glycan_involvement": "Glycosylation affects CRP's opsonization function.", "mechanism": "CRP is elevated in bacterial co-infection, complicating COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector function and inflammation.", "mechanism": "IgG mediates adaptive immunity against SARS-CoV-2.", "protein": "Immunoglobulin G", "relationship_type": "protective", "source_pmcid": "PMC8959282" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects transferrin's half-life and receptor binding.", "mechanism": "Transferrin saturation may be altered in severe inflammation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "medium", "disease": "Renal impairment", "glycan_involvement": "Altered glycosylation in renal disease may affect CRP clearance.", "mechanism": "CRP is elevated in renal impairment, which is a risk factor for severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC8959282" }, { "confidence": "high", "disease": "Common Variable Immunodeficiency (CVID)", "glycan_involvement": "IgG glycosylation affects anti-inflammatory properties and microbiome interactions.", "mechanism": "IgG therapy modulates gut microbiome and reduces inflammation in CVID mouse models.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "IPEX syndrome", "glycan_involvement": "FOXP3 is O-glycosylated, which may affect stability and function of Tregs.", "mechanism": "FOXP3 mutations disrupt Treg development/function, causing severe autoimmunity.", "protein": "FOXP3", "protein_enriched": { "function": "Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479", "gene_name": "FOXP3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9BZS1" }, "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "Tuberculosis", "glycan_involvement": "LY9 is a heavily glycosylated surface receptor; glycosylation is essential for cell-cell interaction.", "mechanism": "LY9 governs IFN-\u03b3 production in T cells, protecting against mycobacterial infection.", "protein": "LY9 (CD229)", "relationship_type": "protective", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "Chronic mucocutaneous candidiasis (CMC)", "glycan_involvement": "Glycosylation of LY9 modulates receptor function and immune signaling.", "mechanism": "LY9 regulates IL-17/IL-22 production, protecting against candidiasis.", "protein": "LY9 (CD229)", "relationship_type": "protective", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "Common Variable Immunodeficiency (CVID)", "glycan_involvement": "TACI is N-glycosylated; glycosylation affects ligand binding and receptor signaling.", "mechanism": "TNFRSF13B mutations impair B cell function, leading to hypogammaglobulinemia and autoimmunity.", "protein": "TNFRSF13B (TACI)", "protein_enriched": { "function": "Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and ", "gene_name": "TNFRSF13B", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "O14836" }, "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "Activated PI3K delta syndrome (APDS/PASLI)", "glycan_involvement": "PI3K\u03b4 is glycosylated; glycosylation may affect stability and signaling.", "mechanism": "PIK3CD mutations cause kinase hyperactivity, leading to immunodeficiency and lymphoproliferation.", "protein": "PI3K\u03b4 (PIK3CD)", "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus", "glycan_involvement": "Helios may be O-glycosylated, affecting nuclear localization and transcriptional activity.", "mechanism": "IKZF2 mutations disrupt Treg and NK cell function, leading to autoimmunity.", "protein": "IKZF2 (Helios)", "protein_enriched": { "function": "DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Transcriptional repressor. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recrui", "gene_name": "IKZF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2S9" }, "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "medium", "disease": "Hemophagocytic lymphohistiocytosis", "glycan_involvement": "Potential glycosylation may affect protein-protein interactions.", "mechanism": "IKZF2 mutations cause immune dysregulation and HLH.", "protein": "IKZF2 (Helios)", "protein_enriched": { "function": "DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Transcriptional repressor. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recrui", "gene_name": "IKZF4", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9H2S9" }, "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "COVID-19 (in CVID)", "glycan_involvement": "IgG subclass glycosylation modulates effector function and vaccine response.", "mechanism": "Restricted IgG heavy chain subfamily usage in CVID patients after vaccination indicates impaired B cell diversification.", "protein": "Immunoglobulin heavy chain (IgG subclasses)", "relationship_type": "biomarker", "source_pmcid": "PMC8965239" }, { "confidence": "medium", "disease": "STAT3 dominant negative syndrome (Hyper-IgE syndrome)", "glycan_involvement": "STAT3 O-glycosylation may affect transcriptional activity and immune regulation.", "mechanism": "STAT3 DN mutations reduce mTORC1 signaling, leading to elevated IgE and immune dysregulation.", "protein": "STAT3", "protein_enriched": { "function": "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coa", "gene_name": "Stat3", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G97993TU", "G49108TO" ], "uniprot_id": "P42227" }, "relationship_type": "causal", "source_pmcid": "PMC8965239" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "CLU is a glycoprotein; glycosylation may affect stability and function.", "mechanism": "Serum CLU levels change in AD; used in blood-based diagnostic models.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "RAGE is a glycoprotein; glycosylation modulates ligand binding and signaling.", "mechanism": "Serum RAGE levels differ in MCI converters; involved in amyloid-\u03b2 transport and inflammation.", "protein": "RAGE", "relationship_type": "biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Mild cognitive impairment (MCI)", "glycan_involvement": "Glycosylation may influence CLU's chaperone activity and clearance.", "mechanism": "CLU levels measured to distinguish MCI from controls; included in predictive models.", "protein": "Clusterin (CLU)", "relationship_type": "biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Age-related lung dysfunction", "glycan_involvement": "All are glycoproteins; glycosylation critical for surfactant function.", "mechanism": "Altered expression in aged alveolar macrophage subpopulations; linked to lung aging.", "protein": "Surfactant proteins (SFTPC, SFTPA1, SFTPA2, SFTPB, SFTPD)", "relationship_type": "biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "CD63 is a glycoprotein; glycosylation may affect vesicle targeting.", "mechanism": "CD63+ sEVs from young ADSCs improve frailty parameters in old mice.", "protein": "CD63", "protein_enriched": { "function": "Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activat", "gene_name": "CD63", "glycan_count": 111, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G01650EU", "G02815KT", "G05049YU", "G05962QB", "G07246CJ", "G08290VR", "G08918WF", "G10773YW", "G10819WX", "G11314AS", "G11629QQ", "G18647XP", "G23294PN", "G23984SE", "G27058EU", "G27915IV", "G31852PQ", "G32788FZ", "G36379GD", "G37399XV", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G47644PP", "G51640FO", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G62765YT", "G63041LO", "G64527OM", "G68490OW", "G70232NH", "G70441OD", "G70619PT", "G74724QE", "G76295SF", "G79666IR", "G80479JV", "G80920RR", "G81263BG", "G83229XP", "G83460ZZ", "G85269DF", "G85282JO", "G86880BF", "G90659AW", "G92062TF", "G92275SC", "G93718GY", "G94854LT", "G95177YH", "G95865ZB", "G96091TT", "G01160VV", "G01485JJ", "G02528FI", "G03644CB", "G04657PL", "G06247RL", "G09831WQ", "G11870QZ", "G11911BT", "G12745LE", "G13131HA", "G16125XL", "G20528HD", "G24528MX", "G25451PN", "G27947YN", "G28541PG", "G28622IK", "G29545VG", "G30970QQ", "G31309XD", "G34989PA", "G35541EV", "G37509XX", "G37818NZ", "G40574BA", "G40926MX", "G45526EA", "G46503DX", "G46691LC", "G49906RN", "G51653BI", "G60033FS", "G65414LI", "G67164EE", "G69521XL", "G70888PK", "G71463BG", "G79286RS", "G80075MS", "G81637OR", "G82443XX", "G90382BL", "G96577RX", "G99668VU", "G99679NM", "G15664MX", "G20210JR", "G27126ED", "G62894KT", "G75568BH", "G97993TU", "G49108TO" ], "uniprot_id": "P08962" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Many sEV proteins are glycosylated, influencing uptake and signaling.", "mechanism": "sEVs from young ADSCs reverse frailty and aging phenotypes in mice.", "protein": "Small extracellular vesicle (sEV) proteins", "relationship_type": "therapeutic", "source_pmcid": "PMC8980209" }, { "confidence": "low", "disease": "Osteosarcopenia", "glycan_involvement": "Glycosylation alters CLU's serum detectability.", "mechanism": "FTIR spectroscopy detects serum protein changes; CLU may contribute.", "protein": "Clusterin (CLU)", "relationship_type": "potential biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Cardiovascular diseases", "glycan_involvement": "Glycosylation modulates RAGE-ligand interactions.", "mechanism": "RAGE mediates vascular inflammation and is implicated in CVD risk with aging.", "protein": "RAGE", "relationship_type": "causal/biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "medium", "disease": "Frailty/aging lung", "glycan_involvement": "Glycosylation essential for surfactant protein function.", "mechanism": "Altered surfactant gene expression in aged alveolar macrophages.", "protein": "Surfactant proteins (SFTPC, SFTPA1, SFTPA2, SFTPB, SFTPD)", "relationship_type": "biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "low", "disease": "Sarcopenia", "glycan_involvement": "Glycosylation affects CLU's stability and detection.", "mechanism": "Serum protein changes detected by FTIR may include CLU in sarcopenia.", "protein": "Clusterin (CLU)", "relationship_type": "potential biomarker", "source_pmcid": "PMC8980209" }, { "confidence": "high", "disease": "Chronic lymphocytic leukemia", "glycan_involvement": "CD52 is a glycoprotein; glycosylation affects antibody binding and clearance.", "mechanism": "Alemtuzumab targets CD52 on lymphocytes, depleting malignant B cells.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation of CD52 may modulate immune recognition.", "mechanism": "Alemtuzumab depletes CD52+ T and B cells, reducing autoimmune activity.", "protein": "CD52", "protein_enriched": { "function": "May play a role in carrying and orienting carbohydrate, as well as having a more specific role", "gene_name": "CD52", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P31358" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "N-glycosylation critical for P-glycoprotein stability and function.", "mechanism": "P-glycoprotein modulates drug efflux (e.g., cyclosporine, tacrolimus), affecting immunosuppressant efficacy.", "protein": "P-glycoprotein", "protein_enriched": { "function": "Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of ", "gene_name": "Abcb1a", "glycan_count": 4, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G61263MF", "G36921VW", "G40574BA", "G49108TO" ], "uniprot_id": "P21447" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "IL-2 is glycosylated, affecting secretion and receptor binding.", "mechanism": "Calcineurin inhibitors (cyclosporine, tacrolimus) block IL-2 production, suppressing T cell activation.", "protein": "Interleukin-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "IgA nephropathy", "glycan_involvement": "Aberrant glycosylation of IgA is pathogenic.", "mechanism": "IgA deposition in glomeruli drives nephropathy; mizoribine reduces IgA production.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "Organ transplant rejection", "glycan_involvement": "CD3 complex is glycosylated, influencing antibody binding.", "mechanism": "Muromonab targets CD3, depleting T cells and preventing rejection.", "protein": "T cell receptor CD3 complex", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "medium", "disease": "Organ transplant rejection", "glycan_involvement": "Enzyme is glycosylated, affecting stability.", "mechanism": "Mycophenolate inhibits this enzyme, blocking lymphocyte proliferation.", "protein": "Inosine monophosphate dehydrogenase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "medium", "disease": "Organ transplant rejection", "glycan_involvement": "CAM glycosylation modulates cell-cell interactions.", "mechanism": "Mycophenolic acid glycosylates CAMs, reducing lymphocyte adhesion and inflammation.", "protein": "Cell adhesion molecules (CAMs)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "medium", "disease": "Skin cancer (post-transplant)", "glycan_involvement": "VEGF glycosylation affects secretion and angiogenic activity.", "mechanism": "Sirolimus inhibits VEGF release, reducing cancer risk in transplant recipients.", "protein": "Vascular Endothelial Growth Factor (VEGF)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8987166" }, { "confidence": "medium", "disease": "Nephrotic syndrome", "glycan_involvement": "Aberrant glycosylation of IgA is implicated.", "mechanism": "IgA deposition contributes to nephrotic syndrome; immunosuppressants reduce immune complex formation.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "causal", "source_pmcid": "PMC8987166" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates immune evasion and receptor binding", "mechanism": "Mediates viral entry via binding to ACE2 receptor", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Sulfated glycosaminoglycan chains mediate viral binding", "mechanism": "Serve as viral attachment factors for SARS-CoV-2 and other viruses", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects receptor conformation and virus binding", "mechanism": "Receptor for SARS-CoV-2 Spike protein, enabling viral entry", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8988903" }, { "confidence": "medium", "disease": "Vesicular stomatitis virus infection", "glycan_involvement": "Glycosylation required for proper folding and function", "mechanism": "Mediates viral entry into host cells", "protein": "Vesicular stomatitis virus G glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Targets sialylated glycoproteins; inhibitors block this interaction", "mechanism": "Cleaves sialic acid from host glycoproteins to facilitate viral release", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Sialylation pattern determines host susceptibility", "mechanism": "Serve as receptors for viral hemagglutinin, mediating viral entry", "protein": "Sialic acid-containing glycoproteins", "relationship_type": "causal/protective", "source_pmcid": "PMC8988903" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Bind specific glycan motifs on pathogens", "mechanism": "Recognize viral glycoproteins, initiate immune response; targeted by S. aureus to evade immunity", "protein": "Dendritic cell C-type lectin receptors", "relationship_type": "protective/causal", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "HIV infection", "glycan_involvement": "N-glycosylation modulates receptor function and viral binding", "mechanism": "Primary receptor for HIV entry", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "Herpes simplex virus infection", "glycan_involvement": "Glycosaminoglycan chains mediate viral binding", "mechanism": "Serve as attachment factors for HSV entry", "protein": "Heparan sulfate proteoglycans", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC8988903" }, { "confidence": "medium", "disease": "Asthma", "glycan_involvement": "Sialylation changes affect immune recognition", "mechanism": "Altered glycosylation in airway epithelium may contribute to inflammation and viral susceptibility", "protein": "Sialic acid-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC8988903" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Highly N-glycosylated; glycosylation critical for folding, immune evasion, and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates receptor interaction and immune recognition.", "mechanism": "Facilitates viral entry via ACE2 binding, similar to SARS-CoV-2.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation supports structural integrity of the virion.", "mechanism": "Maintains virion shape and assembly.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not specified; likely minimal glycosylation.", "mechanism": "Involved in virus assembly, release, and pathogenesis via ion channel activity.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; phosphorylation is main modification.", "mechanism": "Packages viral RNA and interacts with M protein for virion assembly.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 may affect S protein binding affinity.", "mechanism": "Acts as the host receptor for S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry (via DPP4, not ACE2).", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect receptor function and antibody binding.", "mechanism": "Targeted by tocilizumab to suppress cytokine storm in severe COVID-19.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8989131" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation shields epitopes, modulating immune activation.", "mechanism": "Triggers immune response leading to ARDS in severe COVID-19.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8989131" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antibody accessibility and neutralization.", "mechanism": "Targeted by neutralizing antibodies (e.g., convalescent plasma) and entry inhibitors.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8989131" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S-protein is essential for proper folding, immune evasion, and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on human respiratory cells.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC8989132" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation modulates receptor binding and immune recognition.", "mechanism": "Mediates viral entry via ACE2, similar to SARS-CoV-2.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC8989132" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation affects receptor interaction and immune evasion.", "mechanism": "Mediates viral entry via DPP4 receptor.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC8989132" }, { "confidence": "medium", "disease": "Common cold (HCoV-229E, HCoV-NL63, HCoV-OC43, HKU1)", "glycan_involvement": "Glycosylation required for infectivity and immune escape.", "mechanism": "Mediates viral entry into host cells.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC8989132" }, { "confidence": "medium", "disease": "Common cold (HCoV-OC43)", "glycan_involvement": "Recognizes and modifies host sialylated glycans.", "mechanism": "Facilitates viral entry and release by interacting with sialic acids.", "protein": "Hemagglutinin esterase", "relationship_type": "causal", "source_pmcid": "PMC8989132" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation of S protein affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry into host cells via ACE2 receptor binding.", "protein": "Spike (S) protein (SARS-CoV)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation shields epitopes, modulates infectivity and immune recognition.", "mechanism": "Facilitates viral entry into human cells through ACE2 interaction.", "protein": "Spike (S) protein (SARS-CoV-2)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "high", "disease": "Middle East Respiratory Syndrome (MERS)", "glycan_involvement": "Glycosylation influences receptor binding and antigenicity.", "mechanism": "Enables viral entry via DPP4 receptor binding.", "protein": "Spike (S) protein (MERS-CoV)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "medium", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation of ACE2 modulates S protein binding affinity.", "mechanism": "Serves as host cell entry receptor for SARS-CoV S protein.", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Glycosylation affects tropism and immune evasion.", "mechanism": "Mediates entry into host cells, causing mild respiratory infection.", "protein": "Spike (S) protein (HCoV-229E)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Glycosylation modulates host interaction and immune response.", "mechanism": "Facilitates viral entry, leading to upper respiratory tract infection.", "protein": "Spike (S) protein (HCoV-OC43)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "medium", "disease": "Atypical pneumonia", "glycan_involvement": "Glycosylation impacts immune recognition and pathogenesis.", "mechanism": "Viral entry and replication in lower respiratory tract causes pneumonia.", "protein": "Spike (S) protein (SARS-CoV)", "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "high", "disease": "Severe Acute Respiratory Syndrome (SARS)", "glycan_involvement": "Glycosylation influences antigenicity and vaccine design.", "mechanism": "Targeted by neutralizing antibodies and vaccine candidates.", "protein": "Spike (S) protein (SARS-CoV)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8989432" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and vaccine efficacy.", "mechanism": "Basis for mRNA and protein-based vaccines.", "protein": "Spike (S) protein (SARS-CoV-2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC8989432" }, { "confidence": "medium", "disease": "Common cold (HCoV-OC43)", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Assists in viral entry and release.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC8989432" }, { "confidence": "high", "disease": "lung cancer", "glycan_involvement": "N-glycosylation regulates MET processing and trafficking, affecting its function in cancer.", "mechanism": "MET is a receptor tyrosine kinase for HGF; its amplification is associated with lung cancer progression and TKI resistance.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC8990816" }, { "confidence": "high", "disease": "TKI resistance", "glycan_involvement": "N-glycosylation is required for proper MET processing; inhibition of N-glycosylation suppresses MET trafficking.", "mechanism": "Amplification and altered processing of MET contribute to resistance against tyrosine kinase inhibitors in lung cancer.", "protein": "MET", "protein_enriched": { "function": "Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including pr", "gene_name": "MET", "glycan_count": 74, "glycosylation_sites_count": 14, "glytoucan_ids": [ "G06356OH", "G07246CJ", "G43223CG", "G50856PC", "G56518TU", "G62765YT", "G80479JV", "G80920RR", "G93656SY", "G11629QQ", "G12793SR", "G25418HZ", "G41882MT", "G52527GH", "G59536GA", "G65184UU", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G16125XL", "G27058EU", "G29545VG", "G34989PA", "G35541EV", "G37412TK", "G39471UU", "G41071NU", "G45395BF", "G55132BD", "G58954YZ", "G60834IK", "G61256FT", "G68490OW", "G70441OD", "G76295SF", "G79666IR", "G80075MS", "G81637OR", "G83460ZZ", "G83646BJ", "G85282JO", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92406TI", "G93718GY", "G31916IQ", "G45504EY", "G37995HC", "G82443XX", "G00912UN", "G02815KT", "G10486CT", "G11314AS", "G56784JY", "G59626AS", "G60033FS", "G75983OB", "G90659AW", "G95865ZB", "G98611JV", "G49108TO", "G57321FI", "G69364JQ", "G89098OM", "G34730YF", "G37399XV", "G47518TP", "G67324HN", "G72291OX", "G82463GQ", "G89827JR" ], "uniprot_id": "P08581" }, "relationship_type": "causal", "source_pmcid": "PMC8990816" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation affects antibody binding and immune clearance.", "mechanism": "Targeted by monoclonal antibodies (daratumumab, isatuximab) for MM therapy.", "protein": "CD38", "protein_enriched": { "function": "Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosp", "gene_name": "CD38", "glycan_count": 24, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G00912UN", "G27058EU", "G31852PQ", "G45395BF", "G62765YT", "G70232NH", "G76295SF", "G79666IR", "G80920RR", "G90382BL", "G02815KT", "G12341GU", "G15664MX", "G41247ZX", "G46503DX", "G49018RC", "G72747WU", "G01650EU", "G28541PG", "G37399XV", "G47644PP", "G63041LO", "G77669RF", "G95865ZB" ], "uniprot_id": "P28907" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9011801" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation may modulate receptor stability and immune recognition.", "mechanism": "Targeted by CAR-T and bispecific antibodies for MM cell elimination.", "protein": "BCMA (TNFRSF17)", "protein_enriched": { "function": "Acts as an acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GSDMD, GAP43, ZDHHC6 or HRAS (PubMed:21152083, PubMed:2882", "gene_name": "LYPLA2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O95372" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9011801" }, { "confidence": "high", "disease": "AL Amyloidosis", "glycan_involvement": "Glycosylation can affect aggregation propensity and tissue deposition.", "mechanism": "Monoclonal light chains aggregate and deposit as amyloid, causing organ toxicity.", "protein": "Immunoglobulin Light Chain", "relationship_type": "causal", "source_pmcid": "PMC9011801" }, { "confidence": "high", "disease": "Light Chain Deposition Disease (LCDD)", "glycan_involvement": "Glycosylation may influence renal deposition and clearance.", "mechanism": "Monoclonal light chains deposit in kidney, leading to renal failure.", "protein": "Immunoglobulin Light Chain", "relationship_type": "causal", "source_pmcid": "PMC9011801" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation required for secretion and receptor interaction.", "mechanism": "Produced by IFN-responsive neutrophils in MM bone marrow, promotes plasma cell survival.", "protein": "BAFF (TNFSF13B)", "protein_enriched": { "function": "Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell ", "gene_name": "TNFSF13B", "glycan_count": 3, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G28541PG", "G92135MA", "G49108TO" ], "uniprot_id": "Q9Y275" }, "relationship_type": "causal", "source_pmcid": "PMC9011801" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation modulates receptor-ligand binding and cell trafficking.", "mechanism": "Upregulated on neutrophils in MM, mediates recruitment and activation in tumor microenvironment.", "protein": "CXCR1/2", "relationship_type": "biomarker", "source_pmcid": "PMC9011801" }, { "confidence": "high", "disease": "AL Amyloidosis", "glycan_involvement": "Glycosylation affects stability and detection in serum.", "mechanism": "Elevated levels indicate cardiac involvement and predict survival.", "protein": "NT-proBNP", "protein_enriched": { "function": "Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:1672777, PubMed:17372040, PubMed:1914098, PubMed:9458824). May also function as a paracrine antifibrotic factor in t", "gene_name": "NPPB", "glycan_count": 1, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G57321FI" ], "uniprot_id": "P16860" }, "relationship_type": "biomarker", "source_pmcid": "PMC9011801" }, { "confidence": "high", "disease": "Minimal Residual Disease (MRD)", "glycan_involvement": "Glycosylation may affect detection sensitivity.", "mechanism": "Detection by mass spectrometry in serum/urine tracks residual disease.", "protein": "Immunoglobulin Light Chain", "relationship_type": "biomarker", "source_pmcid": "PMC9011801" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation essential for selectin function and shedding.", "mechanism": "Shedding of CD62L on neutrophils indicates activation in MM microenvironment.", "protein": "CD62L (SELL)", "relationship_type": "biomarker", "source_pmcid": "PMC9011801" }, { "confidence": "medium", "disease": "Multiple Myeloma", "glycan_involvement": "Glycosylation modulates receptor signaling and ligand binding.", "mechanism": "IL6R on neutrophils mediates response to stromal IL6, promoting tumor-supportive inflammation.", "protein": "IL6R", "relationship_type": "causal", "source_pmcid": "PMC9011801" }, { "confidence": "medium", "disease": "Metabolic syndrome", "glycan_involvement": "Not specified in article.", "mechanism": "FXR regulates glucose and lipid homeostasis; activation by ligands (e.g., ivermectin) ameliorates metabolic syndrome features.", "protein": "Farnesoid X receptor (FXR)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9045589" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Insulin receptor is a glycoprotein; glycosylation affects receptor function and signaling.", "mechanism": "Insulin resistance in neurons (via insulin receptor desensitization) increases vulnerability to excitotoxicity.", "protein": "Insulin Receptor", "relationship_type": "causal", "source_pmcid": "PMC9045590" }, { "confidence": "medium", "disease": "Stroke", "glycan_involvement": "Glycosylation of insulin receptor may modulate neuronal response to injury.", "mechanism": "Insulin resistance increases neuronal damage after stroke.", "protein": "Insulin Receptor", "relationship_type": "causal", "source_pmcid": "PMC9045590" }, { "confidence": "medium", "disease": "Cognitive Deficits", "glycan_involvement": "Altered glycosylation may affect receptor trafficking and signaling.", "mechanism": "Impaired insulin signaling in neurons contributes to cognitive deficits.", "protein": "Insulin Receptor", "relationship_type": "causal", "source_pmcid": "PMC9045590" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Not specified.", "mechanism": "Blunted Akt activation indicates impaired insulin signaling in insulin resistance.", "protein": "Akt", "protein_enriched": { "function": "AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, gro", "gene_name": "Akt1", "glycan_count": 1, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P47196" }, "relationship_type": "biomarker", "source_pmcid": "PMC9045590" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Not specified.", "mechanism": "Downregulation of pGSK-3\u03b2 is associated with insulin resistance; GSK-3\u03b2 inhibitor ameliorates effects.", "protein": "GSK-3\u03b2", "protein_enriched": { "function": "Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosph", "gene_name": "GSK3B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P49841" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9045590" }, { "confidence": "low", "disease": "Stroke", "glycan_involvement": "Not specified.", "mechanism": "Increased PICK1 expression may mediate enhanced glutamate excitotoxicity in insulin-resistant neurons.", "protein": "PICK1", "protein_enriched": { "function": "Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various recept", "gene_name": "PICK1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NRD5" }, "relationship_type": "causal", "source_pmcid": "PMC9045590" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 on host cells.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "causal", "source_pmcid": "PMC9055790" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ACE2-spike binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2; blocking interaction prevents infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9055790" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate protease activity.", "mechanism": "TMPRSS2 primes spike protein for membrane fusion and viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9055790" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation impacts antigenicity and immune recognition.", "mechanism": "Spike protein is detected in diagnostic assays and targeted by vaccines.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "biomarker", "source_pmcid": "PMC9055790" }, { "confidence": "high", "disease": "Cytokine Release Syndrome (CRS)", "glycan_involvement": "Glycosylation required for secretion and stability.", "mechanism": "Elevated IL-6 drives hyperinflammation in severe COVID-19.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9055790" }, { "confidence": "medium", "disease": "Cytokine Release Syndrome (CRS)", "glycan_involvement": "Glycosylation modulates cytokine activity.", "mechanism": "High IL-10 levels reflect immune dysregulation in severe COVID-19.", "protein": "IL-10", "protein_enriched": { "function": "Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanisti", "gene_name": "IL10", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P22301" }, "relationship_type": "biomarker", "source_pmcid": "PMC9055790" }, { "confidence": "medium", "disease": "Cytokine Release Syndrome (CRS)", "glycan_involvement": "Glycosylation affects secretion and receptor binding.", "mechanism": "TNF-\u03b1 is a key mediator of inflammation in severe COVID-19.", "protein": "TNF-\u03b1", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9055790" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "MXene interaction may disrupt glycan shield, exposing or altering epitopes.", "mechanism": "MXenes adsorb and structurally deform spike protein, inhibiting ACE2 interaction and viral entry.", "protein": "SARS-CoV-2 Spike protein (S)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9055790" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not directly glycosylated, but may affect glycoprotein processing.", "mechanism": "MXene exposure alters host protein interactions with viral non-structural proteins, inhibiting replication.", "protein": "NSP7/NSP10/NSP15", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9055790" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylation enables MXene adsorption via hydrogen bonding.", "mechanism": "Removal of IL-6 by MXene-based hemoperfusion improves survival in sepsis and severe COVID-19.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9055790" }, { "confidence": "medium", "disease": "Evans syndrome", "glycan_involvement": "Spike protein is heavily glycosylated, which may enhance immune cross-reactivity.", "mechanism": "Molecular mimicry between spike protein and erythrocyte/platelet antigens triggers autoimmunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "medium", "disease": "Autoimmune hemolytic anemia (AIHA)", "glycan_involvement": "Glycosylation of spike protein may affect immune recognition.", "mechanism": "Sequence homology with erythrocyte ankyrin-1 may induce autoantibodies.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Sialic acid residues on platelets interact with spike protein, promoting clearance.", "mechanism": "Potential molecular mimicry with platelet glycoproteins; sialic acid-mediated interactions.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation may modulate antigenicity and clearance.", "mechanism": "Autoantibodies target GPIIb/IIIa, leading to platelet destruction.", "protein": "Platelet GPIIb/IIIa", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "Autoimmune hemolytic anemia (AIHA)", "glycan_involvement": "Glycosylation may affect immune recognition.", "mechanism": "Autoantibodies against Rh antigen cause RBC destruction.", "protein": "Red blood cell Rh antigen", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "Evans syndrome", "glycan_involvement": "C3d is a glycoprotein fragment; glycosylation may affect complement activation.", "mechanism": "C3d deposition detected by direct Coombs test indicates complement-mediated hemolysis.", "protein": "C3d", "relationship_type": "biomarker", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "Evans syndrome", "glycan_involvement": "IgG Fc glycosylation modulates effector function and clearance.", "mechanism": "IgG autoantibodies detected on RBCs/platelets by direct Coombs test.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9066390" }, { "confidence": "medium", "disease": "Autoimmune hemolytic anemia (AIHA)", "glycan_involvement": "Glycosylation status not specified but may influence antigenicity.", "mechanism": "Molecular mimicry with SARS-CoV-2 spike protein may trigger autoimmunity.", "protein": "Ankyrin-1 (ANK-1)", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "medium", "disease": "Immune thrombocytopenia (ITP)", "glycan_involvement": "Terminal sialic acids are key for hepatic clearance and viral binding.", "mechanism": "Sialic acid-dependent interactions between platelets and viruses enhance platelet clearance.", "protein": "Sialic acid residues", "relationship_type": "causal", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its function.", "mechanism": "Elevated CRP indicates inflammation in COVID-19 and Evans syndrome.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9066390" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation modulates viral binding.", "mechanism": "SARS-CoV-2 uses ACE2 for cell entry, including in liver cells.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9070591" }, { "confidence": "medium", "disease": "Liver dysfunction (LD)", "glycan_involvement": "Glycosylation of ACE2 affects viral interaction and tissue tropism.", "mechanism": "ACE2 expression in liver may mediate SARS-CoV-2-induced liver injury.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9070591" }, { "confidence": "high", "disease": "Liver dysfunction (LD)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP indicates inflammation and correlates with LD severity in COVID-19.", "protein": "CRP", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "Crp", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P14847" }, "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "medium", "disease": "Liver dysfunction (LD)", "glycan_involvement": "Albumin glycosylation status may affect its half-life and function.", "mechanism": "Low serum albumin is associated with LD and poor prognosis in COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "D-dimer is a glycopeptide; glycosylation influences clearance.", "mechanism": "Elevated D-dimer reflects increased coagulation and is associated with LD in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "Fibrinogen glycosylation modulates clot formation.", "mechanism": "Fibrinogen levels are altered in COVID-19 and LD, indicating coagulopathy.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "medium", "disease": "Liver dysfunction (LD)", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated LDH is associated with tissue injury and LD in COVID-19.", "protein": "LDH", "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "high", "disease": "Liver dysfunction (LD)", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated AST defines LD in COVID-19 patients.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "high", "disease": "Liver dysfunction (LD)", "glycan_involvement": "Minor glycosylation; not central to function.", "mechanism": "Elevated ALT defines LD in COVID-19 patients.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9070591" }, { "confidence": "medium", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation modulates ACE2 function in kidney.", "mechanism": "ACE2 expression in kidney may mediate SARS-CoV-2-induced injury, associated with LD.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9070591" }, { "confidence": "high", "disease": "Anti-synthetase syndrome", "glycan_involvement": "As an IgG autoantibody, glycosylation affects stability and immune complex formation.", "mechanism": "Presence of anti-Jo-1 autoantibody is diagnostic and correlates with disease phenotype.", "protein": "Anti-Jo-1 antibody (anti-histidyl-tRNA synthetase antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "high", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "IgG glycosylation modulates effector function.", "mechanism": "Anti-Jo-1 is a myositis-specific autoantibody found in a subset of IIM.", "protein": "Anti-Jo-1 antibody (anti-histidyl-tRNA synthetase antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "medium", "disease": "Interstitial lung disease (ILD)", "glycan_involvement": "IgG glycosylation may affect immune complex deposition in lung tissue.", "mechanism": "Anti-Jo-1 positivity is associated with increased risk of ILD in IIM.", "protein": "Anti-Jo-1 antibody (anti-histidyl-tRNA synthetase antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "medium", "disease": "Peripheral neuropathy", "glycan_involvement": "IgG glycosylation may influence pathogenicity in nerve tissue.", "mechanism": "Rarely, anti-Jo-1 positive anti-synthetase syndrome presents with peripheral neuropathy, possibly via vasculitis.", "protein": "Anti-Jo-1 antibody (anti-histidyl-tRNA synthetase antibody)", "relationship_type": "causal", "source_pmcid": "PMC9070981" }, { "confidence": "low", "disease": "Valvular heart disease (prosthetic aortic valve stenosis)", "glycan_involvement": "IgG glycosylation may affect immune complex deposition on valves.", "mechanism": "Anti-synthetase syndrome may contribute to prosthetic valve stenosis, possibly via immune-mediated mechanisms.", "protein": "Anti-Jo-1 antibody (anti-histidyl-tRNA synthetase antibody)", "relationship_type": "causal", "source_pmcid": "PMC9070981" }, { "confidence": "medium", "disease": "Anti-synthetase syndrome", "glycan_involvement": "Therapeutic IgG glycosylation influences anti-inflammatory effects.", "mechanism": "IVIG used as immunomodulatory therapy in severe cases.", "protein": "Immunoglobulin G (IVIG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9070981" }, { "confidence": "low", "disease": "Anti-synthetase syndrome", "glycan_involvement": "C3 is N-glycosylated, affecting stability and function.", "mechanism": "C3 levels monitored to assess immune activation.", "protein": "Complement component 3 (C3)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "low", "disease": "Anti-synthetase syndrome", "glycan_involvement": "C4 is N-glycosylated, affecting complement activation.", "mechanism": "C4 levels monitored to assess immune activation.", "protein": "Complement component 4 (C4)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "medium", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "IgG glycosylation modulates immune complex formation.", "mechanism": "ANA positivity supports autoimmune etiology.", "protein": "Anti-nuclear antibody (ANA)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "low", "disease": "Idiopathic inflammatory myopathies (IIM)", "glycan_involvement": "IgG glycosylation affects pathogenicity.", "mechanism": "Anti-dsDNA tested to rule out overlap with other autoimmune diseases.", "protein": "Anti-double-stranded DNA antibody (anti-dsDNA)", "relationship_type": "biomarker", "source_pmcid": "PMC9070981" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry into host cells via ACE2 binding; key for infection and immune response.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9099323" }, { "confidence": "high", "disease": "Chronic Leukemia (CLL/CML)", "glycan_involvement": "Heavily N- and O-glycosylated; glycosylation affects cell-cell interactions and signaling.", "mechanism": "Upregulated in leukemia; involved in immune cell signaling and antigen binding.", "protein": "PTPRC (CD45)", "relationship_type": "biomarker", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation may modulate spike protein binding and immune evasion.", "mechanism": "Direct docking with SARS-CoV-2 spike glycoprotein and Mpro suggests potential for viral interaction in leukemic blood.", "protein": "PTPRC (CD45)", "relationship_type": "causal", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "Chronic Leukemia (CLL/CML)", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement reported.", "mechanism": "Upregulated in leukemia; regulates transcription and immune response.", "protein": "BCL6", "protein_enriched": { "function": "Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.", "gene_name": "BCL6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41182" }, "relationship_type": "biomarker", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Docking with SARS-CoV-2 spike glycoprotein and Mpro suggests possible role in viral-host interactions in leukemia.", "protein": "BCL6", "protein_enriched": { "function": "Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.", "gene_name": "BCL6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P41182" }, "relationship_type": "causal", "source_pmcid": "PMC9099323" }, { "confidence": "high", "disease": "Chronic Leukemia (CLL/CML)", "glycan_involvement": "N-glycosylation required for proper folding and cell surface expression.", "mechanism": "Upregulated in leukemia; regulates cell proliferation and differentiation.", "protein": "KIT (CD117)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation may influence interaction with viral proteins.", "mechanism": "Docking with SARS-CoV-2 spike glycoprotein and Mpro suggests potential for viral interaction in leukemic blood.", "protein": "KIT (CD117)", "relationship_type": "causal", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "Chronic Leukemia (CLL/CML)", "glycan_involvement": "Not a classical glycoprotein; no direct glycan involvement.", "mechanism": "Top hub gene in leukemia; regulates cytoskeleton and cell entry processes.", "protein": "CDC42", "protein_enriched": { "function": "Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses", "gene_name": "CDC42", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60953" }, "relationship_type": "biomarker", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No direct glycan involvement.", "mechanism": "Docking with SARS-CoV-2 spike glycoprotein and Mpro; implicated in viral entry processes.", "protein": "CDC42", "protein_enriched": { "function": "Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses", "gene_name": "CDC42", "glycan_count": 1, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60953" }, "relationship_type": "causal", "source_pmcid": "PMC9099323" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N-glycosylation critical for stability and immune recognition.", "mechanism": "Involved in antigen presentation and immune response to viral infection.", "protein": "HLA-E", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9099323" }, { "confidence": "high", "disease": "Acute disseminated encephalomyelitis (ADEM)", "glycan_involvement": "MOG is a glycoprotein; its glycosylation may influence antigenicity and antibody recognition.", "mechanism": "Anti-MOG antibodies are associated with ADEM, indicating immune-mediated demyelination targeting MOG.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC9099328" }, { "confidence": "medium", "disease": "Transverse myelitis", "glycan_involvement": "Glycosylation of MOG may modulate immune response and pathogenicity.", "mechanism": "Anti-MOG antibodies can be present in transverse myelitis, reflecting immune attack on MOG-expressing myelin.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC9099328" }, { "confidence": "high", "disease": "IgA vasculitis (IgAV)", "glycan_involvement": "IgA is a glycoprotein; glycosylation affects immune complex formation and clearance.", "mechanism": "Circulating immune complexes of IgA deposit in vessel walls, triggering vasculitis.", "protein": "IgA", "relationship_type": "causal", "source_pmcid": "PMC9109862" }, { "confidence": "medium", "disease": "IgA vasculitis (IgAV)", "glycan_involvement": "Bacterial glycoprotein antigens stimulate IgA response; glycosylation patterns may affect immunogenicity.", "mechanism": "TB infection provides glycoprotein antigens that trigger IgA immune complex formation.", "protein": "Mycobacterium tuberculosis glycoprotein antigen", "relationship_type": "causal/trigger", "source_pmcid": "PMC9109862" }, { "confidence": "medium", "disease": "IgA vasculitis (IgAV)", "glycan_involvement": "C3 is a glycoprotein; glycosylation may modulate complement activation.", "mechanism": "C3 deposition in vessel walls detected by immunofluorescence in IgAV.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "medium", "disease": "Latent Tuberculosis Infection (LTBI)", "glycan_involvement": "PPD contains glycoprotein components; glycosylation may affect antigenicity.", "mechanism": "PPD is used in the tuberculin skin test to detect immune response to TB antigens.", "protein": "Purified Protein Derivative (PPD)", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "IgA glycosylation influences immune complex formation and clearance.", "mechanism": "IgA immune complexes may be elevated in TB and contribute to immune pathology.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "medium", "disease": "Tuberculosis", "glycan_involvement": "Bacterial glycosylation patterns modulate host-pathogen interactions.", "mechanism": "Glycoprotein antigens from M. tuberculosis elicit host immune response.", "protein": "Mycobacterium tuberculosis glycoprotein antigen", "relationship_type": "causal", "source_pmcid": "PMC9109862" }, { "confidence": "low", "disease": "Tuberculosis", "glycan_involvement": "C3 glycosylation can affect complement pathway activity.", "mechanism": "Complement activation (C3) may be involved in immune response to TB.", "protein": "C3", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "low", "disease": "Drug-resistant Tuberculosis", "glycan_involvement": "Glycosylation state may influence immune complex formation.", "mechanism": "IgA immune complexes may be present in TB regardless of drug resistance.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "low", "disease": "Tuberculous meningitis", "glycan_involvement": "Glycoprotein content may affect test sensitivity.", "mechanism": "PPD-based tests may assist in diagnosis of TBM.", "protein": "Purified Protein Derivative (PPD)", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "low", "disease": "Stevens-Johnson syndrome", "glycan_involvement": "Glycosylation may modulate immune complex pathogenicity.", "mechanism": "Immune complexes (including IgA) may be involved in SJS pathogenesis.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC9109862" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Azurocidin is a glycoprotein; glycosylation may affect stability and secretion.", "mechanism": "Elevated serum levels correlate with disease severity and mortality; reflects endothelial dysfunction and vascular leakage.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9152632" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-1\u03b2 is glycosylated; glycosylation may modulate secretion and activity.", "mechanism": "Elevated serum levels correlate with disease severity and mortality; drives cytokine storm and inflammation.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "biomarker", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "Systemic multi-organ failure", "glycan_involvement": "Glycosylation may influence interaction with endothelium.", "mechanism": "High levels may indicate risk for systemic organ failure due to vascular leakage.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "Systemic multi-organ failure", "glycan_involvement": "Glycosylation may affect cytokine stability.", "mechanism": "Key mediator of cytokine storm leading to organ failure.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "Sepsis", "glycan_involvement": "Glycosylation may affect function in immune response.", "mechanism": "Associated with organ dysfunction and used for triage in sepsis.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation may modulate interaction with lung endothelium.", "mechanism": "Correlates with lung involvement and predicts progression.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation may affect cytokine activity.", "mechanism": "Drives inflammation and alveolar-capillary barrier disruption.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC9152632" }, { "confidence": "low", "disease": "Acute kidney injury", "glycan_involvement": "Glycosylation may influence renal targeting.", "mechanism": "Associated with kidney dysfunction in severe infection.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect endothelial interactions.", "mechanism": "Induces endothelial permeability and vascular leakage, contributing to severe COVID-19 pathology.", "protein": "Azurocidin (Heparin-binding protein, HBP)", "relationship_type": "causal", "source_pmcid": "PMC9152632" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate immune signaling.", "mechanism": "Promotes cytokine storm and hyperinflammation in severe COVID-19.", "protein": "Interleukin-1\u03b2 (IL-1\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC9152632" }, { "confidence": "high", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "AQP4 is a glycoprotein; glycosylation may affect antigenicity and antibody binding.", "mechanism": "AQP4 antibodies are diagnostic for NMOSD; autoimmunity targets AQP4 on astrocytes.", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC9188454" }, { "confidence": "medium", "disease": "Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA)", "glycan_involvement": "Glycosylation may modulate immune recognition of AQP4.", "mechanism": "AQP4 antibodies indicate CNS autoimmunity triggered post-vaccination (ASIA context).", "protein": "Aquaporin-4", "protein_enriched": { "function": "Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient (PubMed:105", "gene_name": "AQP9", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O43315" }, "relationship_type": "biomarker", "source_pmcid": "PMC9188454" }, { "confidence": "medium", "disease": "Neuromyelitis optica spectrum disorder (NMOSD)", "glycan_involvement": "MOG is a glycoprotein; glycosylation affects antigenicity.", "mechanism": "MOG antibodies are tested to differentiate NMOSD subtypes.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC9188454" }, { "confidence": "medium", "disease": "Multiple Sclerosis", "glycan_involvement": "Glycosylation of MOG influences immune response.", "mechanism": "MOG antibodies are associated with demyelinating diseases including MS.", "protein": "Myelin oligodendrocyte glycoprotein (MOG)", "protein_enriched": { "function": "Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication", "gene_name": "MOG", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "Q16653" }, "relationship_type": "biomarker", "source_pmcid": "PMC9188454" }, { "confidence": "high", "disease": "Alpha-1 antitrypsin deficiency", "glycan_involvement": "Glycosylation affects folding, stability, and secretion; misfolded glycoprotein accumulates.", "mechanism": "Mutations in SERPINA1 gene lead to deficient or dysfunctional glycoprotein, causing disease.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "high", "disease": "Chronic obstructive pulmonary disease (COPD)", "glycan_involvement": "Glycosylation required for secretion; misfolded forms are retained in hepatocytes.", "mechanism": "Deficiency of glycoprotein leads to unopposed neutrophil elastase activity, damaging lung tissue.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "high", "disease": "Liver disease", "glycan_involvement": "Aberrant glycosylation leads to polymerization and retention in ER.", "mechanism": "Accumulation of misfolded glycoprotein in hepatocytes causes liver injury.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "O-glycosylation of MUC1 is critical for its function and trafficking.", "mechanism": "Mutations in MUC1 cause toxic protein accumulation in renal tubules.", "protein": "Mucin-1 (MUC1)", "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "high", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "N-glycosylation is essential for UMOD secretion and function.", "mechanism": "Mutations in UMOD glycoprotein lead to abnormal protein folding and kidney dysfunction.", "protein": "UMOD (Uromodulin)", "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "Chronic kidney disease (CKD)", "glycan_involvement": "Glycosylation affects collagen assembly and stability.", "mechanism": "Mutations in glycosylated collagen IV alpha-5 chain disrupt glomerular basement membrane.", "protein": "COL4A5", "protein_enriched": { "function": "Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen", "gene_name": "COL4A5", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P29400" }, "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "Low-grade glioma (LGG)", "glycan_involvement": "PSG8 is a heavily glycosylated protein; glycosylation may modulate cell adhesion.", "mechanism": "High PSG8-AS1 expression correlates with better survival and cell adhesion gene expression.", "protein": "Pregnancy Specific Glycoprotein 8 (PSG8)", "relationship_type": "protective", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "Glioblastoma (GBM)", "glycan_involvement": "Glycosylation may influence PSG8 function in tumor microenvironment.", "mechanism": "Downregulation of PSG8-AS1 associated with tumor progression.", "protein": "Pregnancy Specific Glycoprotein 8 (PSG8)", "relationship_type": "protective", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "Oligodendroglioma", "glycan_involvement": "Glycosylation may affect PSG8-mediated cell interactions in brain.", "mechanism": "High PSG8-AS1 expression correlates with myelin synthesis and better prognosis.", "protein": "Pregnancy Specific Glycoprotein 8 (PSG8)", "relationship_type": "protective", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "Skin disease (panniculitis)", "glycan_involvement": "Glycosylation required for proper secretion and function.", "mechanism": "Deficiency leads to unregulated protease activity causing skin inflammation.", "protein": "Alpha-1 antitrypsin", "protein_enriched": { "function": "Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The ", "gene_name": "SERPINA1", "glycan_count": 267, "glycosylation_sites_count": 3, "glytoucan_ids": [ "G00912UN", "G05933EN", "G06247RL", "G06356OH", "G07799LX", "G08293MJ", "G09528DL", "G10486CT", "G11115RO", "G11629QQ", "G12341GU", "G12793SR", "G15038BD", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G27947YN", "G36131WL", "G36191CD", "G37412TK", "G40926MX", "G43669FQ", "G44211QA", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49739MP", "G50045TK", "G52527GH", "G55216FT", "G59536GA", "G59626AS", "G60033FS", "G66933CM", "G69834CE", "G70087PV", "G77338BR", "G78059CC", "G82830MN", "G83555HU", "G84467IZ", "G85144OK", "G88374WZ", "G92081HT", "G92821YI", "G94917XT", "G95678HJ", "G43417UB", "G49108TO", "G00273SJ", "G01160VV", "G01485JJ", "G01521EA", "G01650EU", "G02030ZB", "G02628JF", "G02815KT", "G02886BB", "G03644CB", "G04657PL", "G04854VP", "G05049YU", "G05962QB", "G06330RB", "G07246CJ", "G07755XJ", "G08146BT", "G08290VR", "G08609CW", "G08918WF", "G10819WX", "G10846ZT", "G11911BT", "G14669DU", "G14972EH", "G14994KB", "G15664MX", "G20706XG", "G22572EH", "G23505EP", "G25079LO", "G25418HZ", "G25451PN", "G25541YH", "G26330YA", "G26403SG", "G27058EU", "G27126ED", "G28541PG", "G28622IK", "G28681TP", "G29299MO", "G29545VG", "G30248BL", "G30521DU", "G30740WO", "G30970QQ", "G31852PQ", "G31916IQ", "G31986NC", "G33416PL", "G33791AF", "G34029GR", "G34989PA", "G35253PZ", "G36442WJ", "G37399XV", "G37509XX", "G37692EO", "G37868ZX", "G37995HC", "G40206WX", "G40574BA", "G40834TG", "G41071NU", "G41247ZX", "G41840AI", "G42124LM", "G42358LZ", "G42962KI", "G43223CG", "G43769HG", "G44215PV", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G47644PP", "G47748JZ", "G49018RC", "G49589RB", "G49906RN", "G51413EV", "G51640FO", "G51653BI", "G54010QB", "G56307ZW", "G56518TU", "G56770VP", "G57317CE", "G57776ZS", "G57776ZU", "G58087IP", "G58954YZ", "G59324HL", "G60177UT", "G60923RB", "G61256FT", "G62765YT", "G63040RU", "G63381RX", "G63980BQ", "G64275UO", "G65184UU", "G66621EA", "G68490OW", "G70223PD", "G70232NH", "G70375MX", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72197KC", "G72291OX", "G72398FA", "G72747WU", "G72787SB", "G72790NZ", "G72797UR", "G73968GN", "G75006KF", "G75568BH", "G75607BQ", "G75983OB", "G76295SF", "G76329HL", "G77459ND", "G77547TA", "G77669RF", "G78502KD", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80920RR", "G81263BG", "G81637OR", "G82463GQ", "G83624CJ", "G83633GK", "G83646BJ", "G84225JN", "G84452RH", "G84862VB", "G85269DF", "G85554PZ", "G86182NS", "G86226EA", "G86500WE", "G86795LJ", "G86880BF", "G87123QX", "G87389XI", "G87661QW", "G89045VA", "G89098OM", "G90382BL", "G90659AW", "G91116OD", "G92135MA", "G92406TI", "G92551JA", "G94470IW", "G95046LV", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G99668VU", "G12728EY", "G29068FM", "G37881RL", "G57888GL", "G64394MX", "G93656SY", "G10488MI", "G11314AS", "G12261QD", "G15127JD", "G20528HD", "G23863VK", "G27915IV", "G31118FR", "G35541EV", "G37818NZ", "G41044JW", "G43734MM", "G49642SA", "G55132BD", "G63041LO", "G63136LV", "G69521XL", "G75418YA", "G75798PH", "G76868JS", "G78649WQ", "G81295CK", "G85282JO", "G90734RJ", "G92275SC", "G00776MW", "G26864OJ", "G28362DW", "G28916LJ", "G39595FH", "G55412XP", "G66088HZ", "G66951WQ", "G71560PC", "G81282CC", "G91473PK" ], "uniprot_id": "P01009" }, "relationship_type": "causal", "source_pmcid": "PMC9192341" }, { "confidence": "medium", "disease": "hepatic damage", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels.", "mechanism": "Elevated AST indicates liver injury, especially with PPI treatment.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "medium", "disease": "hepatic damage", "glycan_involvement": "AP is a glycoprotein; glycosylation modulates its activity and secretion.", "mechanism": "Increased AP suggests possible liver dysfunction with PPI use.", "protein": "alkaline phosphatase (AP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "hepatic damage", "glycan_involvement": "rGT is a glycoprotein; glycosylation is essential for its enzymatic function.", "mechanism": "rGT is a marker of liver injury, though no significant change was observed.", "protein": "gamma glutamyl transferase (rGT)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "hepatic damage", "glycan_involvement": "CK may be glycosylated; glycosylation can affect serum half-life.", "mechanism": "Elevated CK with PPI use may reflect muscle or liver injury.", "protein": "creatine kinase (CK)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation may influence AST's serum detection.", "mechanism": "AST is sometimes used as a marker for cardiac injury.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "cardiovascular disease (CVD)", "glycan_involvement": "Glycosylation affects AP's circulatory stability.", "mechanism": "AP elevation is associated with vascular calcification and CVD risk.", "protein": "alkaline phosphatase (AP)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "obesity", "glycan_involvement": "Glycosylation may modulate AST's serum levels.", "mechanism": "AST levels can be altered in obesity-related liver dysfunction.", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9193500" }, { "confidence": "low", "disease": "Mild Cognitive Impairment (MCI)", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is an inflammatory marker; no significant association with MCI in this study.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC9193624" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Spike protein mediates viral entry by binding to ACE2 receptor on host cells, enabling infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9197568" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects drug binding and immune recognition.", "mechanism": "Spike protein is targeted by antiviral drugs to inhibit viral entry and replication.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence binding pocket and drug accessibility.", "mechanism": "Paritaprevir binds spike protein with high affinity, potentially inhibiting viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycans may modulate ligand binding.", "mechanism": "Elbasvir binds spike protein, possibly blocking function.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect drug interaction.", "mechanism": "Daclatasvir binds spike protein, potentially inhibiting viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence ligand binding.", "mechanism": "Glycyrrhizic acid binds spike protein, may interfere with viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycans may modulate drug binding.", "mechanism": "Glecaprevir, Pibrentasvir, Voxilaprevir, Telaprevir, Grazoprevir bind spike protein, potentially inhibiting function.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect interaction.", "mechanism": "Letermovir binds spike protein; primarily used for CMV but shows binding to spike.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Mutation may alter glycosylation pattern and function.", "mechanism": "Spike protein sequence variation (e.g., D614G) correlates with viral spread and infectivity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC9197568" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans shield epitopes, affecting immunogenicity.", "mechanism": "Spike protein is the main antigenic target for vaccine-induced neutralizing antibodies.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9197568" }, { "confidence": "high", "disease": "Neonatal HSV disease", "glycan_involvement": "gD Abs enriched for glycans promoting FcRn binding, enhancing placental transfer.", "mechanism": "gD-specific IgG1 antibodies mediate neutralizing activity, associated with protection.", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Neonatal HSV disease", "glycan_involvement": "gB Abs have glycans for FcRn and Fc\u03b3RIIIa binding, affecting transfer and effector function.", "mechanism": "gB-specific antibodies are polyfunctional; IgG1 subclass mediates ADCC, contributing to protection.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Neonatal HSV disease", "glycan_involvement": "Fc glycans favor FcRn binding, enhancing transfer.", "mechanism": "Neutralizing activity only; efficiently transferred to newborns.", "protein": "IgG1 anti-gD antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Neonatal HSV disease", "glycan_involvement": "Fc glycans promote both FcRn and Fc\u03b3RIIIa binding.", "mechanism": "Mediates ADCC and neutralization; ADCC Abs transfer less efficiently except in COVID-19.", "protein": "IgG1 anti-gB antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "medium", "disease": "Neonatal HSV disease", "glycan_involvement": "Glycan profile not specified; likely impacts Fc receptor binding.", "mechanism": "Polyfunctional but less efficiently transferred than IgG1.", "protein": "IgG3 anti-gB antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Disseminated neonatal HSV disease", "glycan_involvement": "Fc glycans modulate ADCC and transfer.", "mechanism": "ADCC activity associated with greater protection against disseminated disease.", "protein": "IgG1 anti-gB antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Neonatal HSV disease", "glycan_involvement": "Glycan composition affects FcRn binding and transfer efficiency.", "mechanism": "ADCC Abs transfer poorly to preterm newborns, reducing protection.", "protein": "IgG1 anti-gB antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "medium", "disease": "Neonatal HSV disease", "glycan_involvement": "COVID-19 may alter placental glycan composition, increasing ADCC Ab transfer.", "mechanism": "In mothers with COVID-19, ADCC Abs transfer more efficiently, possibly due to altered placental glycosylation.", "protein": "IgG1 anti-gB antibody", "relationship_type": "protective", "source_pmcid": "PMC9209114" }, { "confidence": "medium", "disease": "Neonatal HSV disease", "glycan_involvement": "Fc glycan enrichment for FcRn binding.", "mechanism": "gD-specific IgG1 Abs serve as markers for neutralizing activity and transfer efficiency.", "protein": "Glycoprotein D (gD)", "protein_enriched": { "function": "Protects virus-infected cells from TNF-induced cytolysis", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P04493" }, "relationship_type": "biomarker", "source_pmcid": "PMC9209114" }, { "confidence": "medium", "disease": "Neonatal HSV disease", "glycan_involvement": "Fc glycan enrichment for FcRn and Fc\u03b3RIIIa binding.", "mechanism": "gB-specific IgG1 Abs indicate ADCC potential and transfer efficiency.", "protein": "Glycoprotein B (gB)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9209114" }, { "confidence": "high", "disease": "Biliary Atresia", "glycan_involvement": "Galectin-3 binds \u03b2-galactoside glycans, mediating cell-cell and cell-matrix interactions in inflammation and fibrosis.", "mechanism": "Galectin-3 plasma levels are elevated in late-stage biliary atresia, correlating with disease severity.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "high", "disease": "Cholestatic Liver Disease (CLD)", "glycan_involvement": "Galectin-3 recognizes glycan structures on cell surfaces, influencing inflammatory signaling.", "mechanism": "Galectin-3 levels are increased in late-stage CLD, indicating disease progression.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "high", "disease": "Liver Fibrosis", "glycan_involvement": "Galectin-3-glycan interactions promote activation of hepatic stellate cells and extracellular matrix deposition.", "mechanism": "Galectin-3 levels positively correlate with fibrosis score, suggesting a role in fibrogenesis.", "protein": "Galectin-3", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Cirrhosis", "glycan_involvement": "Galectin-3 binding to glycans modulates fibrotic and inflammatory pathways leading to cirrhosis.", "mechanism": "Galectin-3 is implicated in progression to cirrhosis; blocking Gal3 may delay disease progression.", "protein": "Galectin-3", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Biliary Atresia", "glycan_involvement": "Inhibition of Galectin-3-glycan interactions may reduce inflammation and fibrosis.", "mechanism": "Targeting Galectin-3 in early BA may delay progression to cirrhosis and reduce need for transplant.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Galectin-3 binding to glycans influences hepatic inflammation and fibrogenesis.", "mechanism": "Galectin-3 correlates with clinical markers of liver injury (ALT, AST, APRI score).", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Biliary Atresia", "glycan_involvement": "Galectin-3-glycan interactions may affect bile duct integrity and function.", "mechanism": "Galectin-3 levels correlate with total bilirubin, indicating cholestatic severity.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Galectin-3 binding to glycans may contribute to hepatocyte dysfunction.", "mechanism": "Galectin-3 negatively correlates with albumin, reflecting worsening liver function.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Liver Fibrosis", "glycan_involvement": "Galectin-3-glycan interactions modulate immune cell activation and cytokine release.", "mechanism": "Galectin-3 correlates with IL-6, linking it to proinflammatory cytokine signaling.", "protein": "Galectin-3", "relationship_type": "biomarker", "source_pmcid": "PMC9209232" }, { "confidence": "medium", "disease": "Cholestatic Liver Disease (CLD)", "glycan_involvement": "Inhibition of Galectin-3-glycan binding may attenuate inflammation and fibrosis.", "mechanism": "Blocking Galectin-3 may delay progression to cirrhosis in pediatric CLD.", "protein": "Galectin-3", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9209232" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein affects receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9212255" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycan shield modulates immunogenicity and antibody accessibility.", "mechanism": "Targeted by vaccines and neutralizing antibodies to block viral entry.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9212255" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 influences S protein binding affinity.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via S protein binding.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9212255" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector functions and half-life.", "mechanism": "Neutralizes SARS-CoV-2 and is used as a biomarker for infection and immunity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9212255" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects stability and immune activation.", "mechanism": "Early marker of infection; neutralizes virus.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC9212255" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor function and antibody binding.", "mechanism": "Targeted by tocilizumab to reduce cytokine storm and inflammation.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9212255" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation mediates cell adhesion and nanoparticle binding.", "mechanism": "Upregulated during inflammation; targeted by nanoparticles for drug delivery.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9212255" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects protein-protein interactions in virion assembly.", "mechanism": "Essential for virus assembly and morphogenesis.", "protein": "Membrane (M) glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9212255" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may affect virion stability.", "mechanism": "Required for virus assembly and release.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC9212255" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Possible O-glycosylation may affect RNA binding and immune recognition.", "mechanism": "Used as a diagnostic marker; involved in viral RNA replication.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC9212255" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "APOL1 is a glycoprotein, but specific glycan involvement not detailed.", "mechanism": "APOL1 high-risk variants increase susceptibility to AKI in individuals with African ancestry, especially during COVID-19.", "protein": "Apolipoprotein L1 (APOL1)", "relationship_type": "causal", "source_pmcid": "PMC9212337" }, { "confidence": "medium", "disease": "Death (mortality in COVID-19)", "glycan_involvement": "APOL1 is glycosylated; direct role of glycosylation not specified.", "mechanism": "APOL1 high-risk variants associated with increased mortality in COVID-19 patients.", "protein": "Apolipoprotein L1 (APOL1)", "relationship_type": "causal", "source_pmcid": "PMC9212337" }, { "confidence": "high", "disease": "Acute Lung Injury (ALI)", "glycan_involvement": "OPN is an N-linked glycoprotein; glycosylation may affect secretion and receptor interaction.", "mechanism": "Kidney-derived OPN acts as a cytokine, increasing lung endothelial permeability and immune cell infiltration after AKI.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC9212337" }, { "confidence": "high", "disease": "AKI-ALI (multiorgan failure)", "glycan_involvement": "N-linked glycosylation of OPN may modulate its cytokine function.", "mechanism": "Circulating OPN mediates kidney-lung crosstalk, driving multiorgan failure.", "protein": "Osteopontin (OPN)", "relationship_type": "causal", "source_pmcid": "PMC9212337" }, { "confidence": "medium", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Glycosylation may influence OPN stability and detection.", "mechanism": "Serum OPN levels correlate with AKI severity.", "protein": "Osteopontin (OPN)", "relationship_type": "biomarker", "source_pmcid": "PMC9212337" }, { "confidence": "high", "disease": "Acute Lung Injury (ALI)", "glycan_involvement": "Glycosylation may affect antibody binding and OPN function.", "mechanism": "Anti-OPN antibody prevents lung injury in AKI models.", "protein": "Osteopontin (OPN)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9212337" }, { "confidence": "medium", "disease": "Acute Lung Injury (ALI)", "glycan_involvement": "CD44 is a glycoprotein; glycosylation may regulate ligand binding.", "mechanism": "Lung CD44 acts as a receptor for OPN, mediating immune cell chemotaxis and lung injury.", "protein": "CD44", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9212337" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation affects antigenicity and immune recognition.", "mechanism": "S protein is detected by serological and antigen-based assays for COVID-19 diagnosis.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antigenicity and detection sensitivity.", "mechanism": "N protein is used as an antigen in ELISA and chemiluminescence assays for COVID-19 diagnosis.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Contains N-glycosylation sites modulating immune response.", "mechanism": "RBD is a target for antibody detection due to its strong antigenicity.", "protein": "Receptor Binding Domain (RBD) of S protein", "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans shield epitopes, modulate receptor binding and immune evasion.", "mechanism": "Mediates viral entry via ACE2 binding, initiating infection.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG is N-glycosylated, affecting effector function and detection.", "mechanism": "Host IgG against S and N proteins indicates prior or ongoing infection.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgM is N-glycosylated, influencing immune response and assay performance.", "mechanism": "Host IgM against S and N proteins indicates recent infection.", "protein": "IgM", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgA is N- and O-glycosylated, modulating mucosal immunity.", "mechanism": "Serum IgA levels correlate with disease severity and can be used for diagnosis.", "protein": "IgA", "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycosylation patterns influence cross-reactivity.", "mechanism": "S protein is used for serological cross-reactivity studies between SARS-CoV and SARS-CoV-2.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation affects antigenicity and detection.", "mechanism": "S protein is used in biosensor-based detection for MERS-CoV.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation may affect detection specificity.", "mechanism": "N protein detection helps differentiate viral pneumonia etiology.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC9217735" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 is critical for viral spike binding.", "mechanism": "CQ/HCQ inhibit glycosylation of ACE2, interfering with SARS-CoV-2 binding and entry.", "protein": "Angiotensin-converting enzyme 2 receptor", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9217737" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike protein is heavily glycosylated, mediating immune evasion and receptor interaction.", "mechanism": "Spike protein binds to glycosylated ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9217737" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation of gp120 is essential for viral entry and immune evasion.", "mechanism": "HCQ inhibits posttranslational modification (glycosylation) of gp120, reducing viral infectivity.", "protein": "HIV envelope glycoprotein gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9217737" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Sialic acids on glycoproteins serve as viral receptors.", "mechanism": "CQ inhibits quinone reductase 2, a neighbor of this enzyme, interfering with sialic acid biosynthesis and thus viral receptor function.", "protein": "UDP-N-acetylglucosamine 2-epimerase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9217737" }, { "confidence": "medium", "disease": "Chikungunya virus infection", "glycan_involvement": "Sialic acid moieties are viral attachment factors.", "mechanism": "CQ interferes with sialic acid biosynthesis, reducing viral binding to cell surface glycoproteins.", "protein": "Cell surface sialylated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9217737" }, { "confidence": "medium", "disease": "Dengue virus infection", "glycan_involvement": "Sialylated glycoproteins mediate viral entry.", "mechanism": "CQ impairs endosomal entry and sialic acid-mediated viral binding.", "protein": "Cell surface sialylated glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9217737" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein binds ACE-2 receptor to mediate viral entry into host cells.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE-2 glycosylation affects spike binding affinity.", "mechanism": "ACE-2 acts as the entry receptor for SARS-CoV-2 via spike protein interaction.", "protein": "Angiotensin-converting enzyme 2 (ACE-2)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutation may alter glycan shield and spike conformation.", "mechanism": "D614G mutation increases spike stability and infectivity, leading to higher transmission.", "protein": "SARS-CoV-2 Spike glycoprotein (D614G variant)", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Glycosylation influences spike-host cell interactions.", "mechanism": "Spike-mediated infection of type II pneumocytes leads to surfactant loss and alveolar collapse.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "medium", "disease": "Multisystem organ failure", "glycan_involvement": "Glycosylation may affect tissue tropism.", "mechanism": "Spike-mediated viral spread to ACE-2 expressing organs causes systemic damage.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may affect immune recognition.", "mechanism": "ORF8 mutations may modulate immune evasion and disease severity.", "protein": "SARS-CoV-2 ORF8 protein (L84S variant)", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Possible glycosylation may modulate function.", "mechanism": "ORF3a mutations may influence viral pathogenicity and host cell death.", "protein": "SARS-CoV-2 ORF3a protein (Q57H variant)", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Limited; N protein is not highly glycosylated.", "mechanism": "N protein is used in diagnostic assays for COVID-19 detection.", "protein": "SARS-CoV-2 Nucleocapsid (N) protein", "relationship_type": "biomarker", "source_pmcid": "PMC9217739" }, { "confidence": "medium", "disease": "Acute cardiac injury", "glycan_involvement": "Glycosylation may affect tissue-specific spike binding.", "mechanism": "ACE-2 expression in heart facilitates viral entry and cardiac damage.", "protein": "Angiotensin-converting enzyme 2 (ACE-2)", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "Pneumonia", "glycan_involvement": "Glycosylation modulates immune evasion and infectivity.", "mechanism": "Spike-mediated infection of lung cells leads to pneumonia.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9217739" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9243985" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects S protein binding and viral entry.", "mechanism": "Acts as the host cell receptor for SARS-CoV-2 S protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9243985" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "Elevated CRP levels correlate with increased inflammation and disease severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9243985" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "LDH is glycosylated; glycosylation may affect serum stability.", "mechanism": "Elevated LDH indicates tissue damage and correlates with severity.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC9243985" }, { "confidence": "medium", "disease": "Severe COVID-19", "glycan_involvement": "Surface glycoproteins mediate immune cell trafficking and activation.", "mechanism": "Altered WBC counts (neutrophilia, lymphopenia) reflect immune dysregulation.", "protein": "White blood cell surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC9243985" }, { "confidence": "high", "disease": "COVID-19 pneumonia", "glycan_involvement": "Glycans modulate immune evasion and cell tropism.", "mechanism": "Initiates infection in lung epithelial cells, leading to pneumonia.", "protein": "SARS-CoV-2 Spike protein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9243985" }, { "confidence": "medium", "disease": "COVID-19 pneumonia", "glycan_involvement": "Glycosylation status may influence tissue tropism.", "mechanism": "Expression in lung tissue enables viral entry and pneumonia development.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9243985" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation is essential for CRP function.", "mechanism": "CRP levels rise in response to infection and inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9243985" }, { "confidence": "low", "disease": "Diabetes", "glycan_involvement": "Altered glycosylation may modulate receptor function.", "mechanism": "ACE2 expression and glycosylation may be altered in diabetes, affecting COVID-19 susceptibility.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9243985" }, { "confidence": "low", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect ACE2 stability and function.", "mechanism": "ACE2 is involved in blood pressure regulation; its interaction with SARS-CoV-2 may worsen outcomes.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9243985" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Viral glycoprotein; glycosylation may affect protein folding and immune evasion.", "mechanism": "Essential for viral RNA replication; inhibition blocks viral replication.", "protein": "NS5 RNA-dependent RNA polymerase (RdRp) domain (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "medium", "disease": "Dengue hemorrhagic fever", "glycan_involvement": "Glycosylation may modulate immune recognition.", "mechanism": "Targeting RdRp may prevent severe disease progression.", "protein": "NS5 RNA-dependent RNA polymerase (RdRp) domain (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "medium", "disease": "Dengue shock syndrome", "glycan_involvement": "Glycosylation may influence protein stability.", "mechanism": "Inhibition of RdRp could reduce viral load and severity.", "protein": "NS5 RNA-dependent RNA polymerase (RdRp) domain (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "E2 is heavily glycosylated; glycans are critical for immune evasion and receptor binding.", "mechanism": "Berberine inhibits HCV replication by targeting E2 glycoprotein, blocking viral entry.", "protein": "E2 glycoprotein (Hepatitis C virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "medium", "disease": "Dengue fever", "glycan_involvement": "Glycosylation may affect enzyme activity and immune evasion.", "mechanism": "Berberine computationally predicted to inhibit NS5 methyltransferase, blocking viral replication.", "protein": "NS5 methyltransferase (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "medium", "disease": "Zika virus disease", "glycan_involvement": "NS3 glycosylation may affect protease function.", "mechanism": "Berberine predicted to inhibit NS3, interfering with viral replication.", "protein": "NS3 protein (Zika virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "high", "disease": "Dengue fever", "glycan_involvement": "Glycosylation may modulate ligand binding and immune evasion.", "mechanism": "Azadirachtin, curcumin, apigenin, andrographolide, and berberine predicted to bind and inhibit RdRp, suppressing viral replication.", "protein": "NS5 RNA-dependent RNA polymerase (RdRp) domain (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "low", "disease": "Dengue fever", "glycan_involvement": "Indirect; glycosylation may affect protein interactions.", "mechanism": "(+)-l-Alliin may reduce inflammation and oxidative stress in dengue-infected cells.", "protein": "NS5 RNA-dependent RNA polymerase (RdRp) domain (Dengue virus)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9281232" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation enables receptor-ligand interactions with viral spike protein.", "mechanism": "Facilitates SARS-CoV-2 entry into host cells, amplifies infection and cytokine storm.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "high", "disease": "Vascular endothelial dysfunction", "glycan_involvement": "Glycosylation modulates ligand binding and receptor function.", "mechanism": "NRP-1 mediates endothelial cell permeability and dysfunction, especially under VEGF hyperactivation.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Immunothrombosis", "glycan_involvement": "Glycosylation affects immune cell interactions.", "mechanism": "NRP-1 involvement in immune cell activation and endothelial dysfunction promotes coagulopathy.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Organ damage (lung, kidney, liver, endocrine)", "glycan_involvement": "Glycosylation supports tissue-specific receptor activity.", "mechanism": "NRP-1 expression in multiple organs mediates SARS-CoV-2 tropism and damage.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "high", "disease": "Neurological disorders (encephalopathy, neuroinflammation)", "glycan_involvement": "Glycosylation enables interaction with neuronal ligands and viral proteins.", "mechanism": "NRP-1 facilitates SARS-CoV-2 neuroinvasion and blood-brain barrier disruption.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Retinopathy", "glycan_involvement": "Glycosylation modulates angiogenic signaling.", "mechanism": "NRP-1 expression linked to retinal vascular pathology.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "high", "disease": "Cancer (lung, prostate, intestinal)", "glycan_involvement": "Glycosylation affects VEGF binding and angiogenic activity.", "mechanism": "NRP-1 promotes tumor angiogenesis and progression.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Proteinuric nephropathy", "glycan_involvement": "Glycosylation influences receptor function in renal tissue.", "mechanism": "NRP-2 involved in cytokine-mediated damage to proximal tubular cells.", "protein": "Neuropilin-2 (NRP-2)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Multiple sclerosis", "glycan_involvement": "Glycosylation supports immune cell adhesion and migration.", "mechanism": "NRP-1 mediates inflammatory cell infiltration and blood-brain barrier destruction.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "causal", "source_pmcid": "PMC9294753" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "Glycosylation may modulate receptor expression and function.", "mechanism": "Increased NRP-1 expression correlates with severity and ACE2 levels in affected brain regions.", "protein": "Neuropilin-1 (NRP-1)", "relationship_type": "biomarker", "source_pmcid": "PMC9294753" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects tropism and infectivity.", "mechanism": "Facilitates entry into host cells via ACE2 receptor.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation influences receptor interaction.", "mechanism": "Binds to DPP4 receptor for host cell entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "HE is a glycoprotein with sialic acid binding activity.", "mechanism": "Assists in virus entry and spread in \u03b2-coronaviruses.", "protein": "Hemagglutinin esterase (HE)", "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity.", "mechanism": "Serves as entry receptor for SARS-CoV-2; blocking S-ACE2 interaction inhibits infection.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9294970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate spike-CD147 interaction.", "mechanism": "Alternative receptor for SARS-CoV-2 entry.", "protein": "CD147 (Basigin)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike glycosylation influences TMPRSS2 cleavage efficiency.", "mechanism": "Cleaves spike protein, facilitating membrane fusion and viral entry.", "protein": "Transmembrane serine protease 2 (TMPRSS2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation near cleavage site modulates furin activity.", "mechanism": "Cleaves spike protein at polybasic site, activating it for fusion.", "protein": "Furin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9294970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion stability and immune recognition.", "mechanism": "Essential for viral assembly and release.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status may influence function.", "mechanism": "Involved in virus maturation and release.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9294970" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Spike protein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9296157" }, { "confidence": "medium", "disease": "Post COVID-encephalopathy", "glycan_involvement": "Glycosylation affects immune evasion and neuroinvasion.", "mechanism": "Spike protein triggers immune response and may contribute to CNS inflammation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9296157" }, { "confidence": "medium", "disease": "Neuropsychiatric symptoms (hallucinations, catatonia, delirium)", "glycan_involvement": "Glycosylation modulates host-pathogen interactions in CNS.", "mechanism": "Spike protein-induced immune dysregulation may lead to neuroinflammation.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9296157" }, { "confidence": "medium", "disease": "Autoimmune encephalopathy", "glycan_involvement": "Calcium channels are glycoproteins; glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against PQ-type calcium channels detected, indicating autoimmune CNS involvement.", "protein": "Calcium channel (PQ type)", "relationship_type": "biomarker", "source_pmcid": "PMC9296157" }, { "confidence": "low", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation may influence spike protein interactions with host coagulation factors.", "mechanism": "COVID-19 infection increases risk of coagulopathy.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9296157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300457" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine efficacy.", "mechanism": "Target for vaccine design; immunogenic epitopes elicit neutralizing antibodies.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Predicted glycosylation may affect immune recognition.", "mechanism": "Contains immunogenic epitopes for T- and B-cell responses; included in multiepitope vaccines.", "protein": "Membrane glycoprotein (M)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may influence immunogenicity.", "mechanism": "Epitope-based vaccines targeting E protein can induce immune response.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein but may interact with glycosylated host factors.", "mechanism": "Highly immunogenic; B- and T-cell epitopes used in vaccine design.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "N-glycosylation patterns conserved; impacts cross-reactivity.", "mechanism": "Mediates viral entry in SARS-CoV; shares sequence and glycosylation similarity with SARS-CoV-2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates immune evasion.", "mechanism": "Mediates viral entry in MERS-CoV; similar function to SARS-CoV-2 S protein.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300457" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated; glycosylation affects S protein binding.", "mechanism": "Viral S protein binds ACE2 to enter host cells; blocking interaction prevents infection.", "protein": "ACE2 (host receptor)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and S protein processing.", "mechanism": "Primes S protein for membrane fusion; inhibition blocks viral entry.", "protein": "TMPRSS2 (host protease)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Contains immunogenic epitopes; included in multiepitope vaccine designs.", "protein": "ORF3a protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300457" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is a glycoprotein; glycosylation affects spike binding affinity.", "mechanism": "Serves as the entry receptor for SARS-CoV-2 via interaction with spike protein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300459" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor interaction.", "mechanism": "Mediates viral entry (via DPP4, not ACE2).", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; acts on glycosylated spike.", "mechanism": "Primes spike protein for membrane fusion, facilitating viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated; processes viral proteins, some of which are glycoproteins.", "mechanism": "Essential for viral polyprotein processing and replication.", "protein": "3CLpro (Main protease, Mpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not glycosylated.", "mechanism": "Catalyzes viral RNA synthesis.", "protein": "RNA-dependent RNA polymerase (RdRp, nsp12)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Not glycosylated.", "mechanism": "N protein production is a marker of viral replication.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9300459" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not glycosylated.", "mechanism": "Degrades viral RNA to evade host immunity.", "protein": "Endoribonuclease (Nsp15)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "Respiratory viral infections (general)", "glycan_involvement": "Glycosylation modulates susceptibility to viral binding.", "mechanism": "ACE2 is a common entry receptor for several coronaviruses.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9300459" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells; essential for infection and pathogenesis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300476" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates immune evasion and receptor interaction.", "mechanism": "Homologous spike protein mediates entry into host cells via ACE2, causing SARS.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300476" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans affect accessibility of neutralizing epitopes.", "mechanism": "Targeted by neutralizing drugs and antibodies to block viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein stability and function.", "mechanism": "Essential for viral assembly, morphology, and pathogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation implicated in virion assembly and immune modulation.", "mechanism": "Major structural protein required for virion assembly.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status debated; may affect antigenicity.", "mechanism": "Abundant viral protein; used in diagnostic assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9300476" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates spike binding affinity.", "mechanism": "Host receptor for spike protein; mediates viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "causal", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "N-glycosylation shields spike from immune recognition.", "mechanism": "MERS-CoV spike mediates entry via DPP4, but glycosylation principles are conserved.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect inhibitor binding.", "mechanism": "Targeted by plant-derived and synthetic inhibitors to block viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300476" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and immunogenicity.", "mechanism": "Used in serological assays for diagnosis and vaccine development.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9300476" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9300480" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects Spike-ACE2 binding affinity.", "mechanism": "Host receptor for SARS-CoV-2 Spike glycoprotein, enabling viral entry.", "protein": "Angiotensin-converting enzyme 2 (ACE2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates drug binding and immune response.", "mechanism": "Carrier protein for drugs; levels may change during infection/inflammation.", "protein": "Alpha-1-acid glycoprotein 1", "relationship_type": "biomarker", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation state may affect function and drug binding.", "mechanism": "Carrier for drugs and endogenous molecules; altered in severe disease.", "protein": "Serum albumin", "relationship_type": "biomarker", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation required for proper folding and function.", "mechanism": "Drug transporter influencing pharmacokinetics of COVID-19 therapeutics.", "protein": "P-glycoprotein 1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antibody binding and effector function.", "mechanism": "Targeted by monoclonal antibody therapies (e.g., Bevacizumab) to modulate immune response.", "protein": "Low-affinity immunoglobulin gamma Fc region receptor III-A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates complement activation and immune complex clearance.", "mechanism": "Targeted by monoclonal antibodies (e.g., Bevacizumab) to modulate complement activation.", "protein": "Complement C1q subcomponent subunit A", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for receptor function and antibody binding.", "mechanism": "Targeted by Tocilizumab to reduce cytokine storm.", "protein": "Interleukin-6 receptor subunit alpha", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect ligand binding and immune modulation.", "mechanism": "Targeted by ATYR1923 to modulate immune response.", "protein": "Neuropilin-2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding and bioactivity.", "mechanism": "Targeted by Bevacizumab to reduce vascular permeability and improve oxygenation.", "protein": "Vascular endothelial growth factor A (VEGF-A)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300480" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via binding to ACE2 on host cells.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9300481" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 affects spike binding affinity.", "mechanism": "Host receptor for spike protein; essential for viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and localization.", "mechanism": "Primes spike protein for membrane fusion.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects trafficking and activity.", "mechanism": "Cleaves spike protein in endosomes, facilitating viral entry.", "protein": "Cathepsin L", "protein_enriched": { "function": "Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone r", "gene_name": "CTSL", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G06110VR", "G06356OH", "G14669DU", "G22310AV", "G28681TP", "G31665QC", "G31852PQ", "G37881RL", "G39188ZX", "G41247ZX", "G43089EG", "G47518TP", "G48414YA", "G49589RB", "G50282JC", "G52527GH", "G62765YT", "G71784JC", "G75983OB", "G80920RR", "G92050GC", "G92275SC", "G96091TT" ], "uniprot_id": "P07711" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "N-glycosylation modulates receptor function and antibody binding.", "mechanism": "IL-6R blockade reduces hyperinflammation in severe COVID-19.", "protein": "IL-6 receptor (IL-6R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation required for receptor stability and signaling.", "mechanism": "IL-1R antagonists (e.g., anakinra) reduce inflammation in severe COVID-19.", "protein": "Interleukin-1 receptor (IL-1R)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation not directly involved in protease activity.", "mechanism": "Essential for viral polyprotein processing.", "protein": "HIV-1 protease", "relationship_type": "causal", "source_pmcid": "PMC9300481" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzyme activity and immune evasion.", "mechanism": "Cleaves sialic acids to release new virions.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect folding and activity.", "mechanism": "Processes viral polyproteins and antagonizes host immune response.", "protein": "PLpro (Papain-like protease)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation not essential for activity but may affect stability.", "mechanism": "Processes viral polyproteins required for replication.", "protein": "Mpro (3CLpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300481" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Mediates viral entry by binding to ACE2 and facilitating membrane fusion.", "protein": "Spike glycoprotein S", "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and vaccine design.", "mechanism": "Targeted by vaccines (Pfizer, Moderna, J&J, AstraZeneca) to elicit neutralizing antibodies.", "protein": "Spike glycoprotein S", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300482" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Mutations may alter glycosylation patterns, impacting immune escape.", "mechanism": "Mutations (e.g., N501Y, D614G) in spike glycoprotein define variants with altered transmissibility.", "protein": "Spike glycoprotein S", "relationship_type": "biomarker", "source_pmcid": "PMC9300482" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is glycosylated, which modulates spike binding affinity.", "mechanism": "Host receptor for spike glycoprotein S, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and spike processing.", "mechanism": "Primes spike glycoprotein S for membrane fusion.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation near cleavage site may regulate furin accessibility.", "mechanism": "Cleaves spike glycoprotein at S1/S2 site, facilitating viral entry.", "protein": "Furin", "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "medium", "disease": "Severe acute respiratory syndrome (SARS)", "glycan_involvement": "Similar glycosylation patterns modulate immune evasion.", "mechanism": "Homologous spike glycoprotein mediates entry in SARS-CoV.", "protein": "Spike glycoprotein S", "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "medium", "disease": "Middle East respiratory syndrome (MERS)", "glycan_involvement": "Glycosylation shields epitopes from immune detection.", "mechanism": "Homologous spike glycoprotein mediates entry in MERS-CoV.", "protein": "Spike glycoprotein S", "relationship_type": "causal", "source_pmcid": "PMC9300482" }, { "confidence": "low", "disease": "Cerebral venous sinus thrombosis (CVST)", "glycan_involvement": "Potential involvement of glycosylation in immune complex formation.", "mechanism": "Adenoviral vector vaccines encoding spike protein associated with rare CVST and thrombocytopenia.", "protein": "Spike glycoprotein S", "relationship_type": "causal (vaccine-induced, rare)", "source_pmcid": "PMC9300482" }, { "confidence": "low", "disease": "Thrombocytopenia", "glycan_involvement": "Possible role of glycosylation in antigenicity and immune response.", "mechanism": "Rare immune-mediated thrombocytopenia after adenoviral vector vaccines encoding spike protein.", "protein": "Spike glycoprotein S", "relationship_type": "causal (vaccine-induced, rare)", "source_pmcid": "PMC9300482" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates immune evasion and receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 receptor on host cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and assay sensitivity.", "mechanism": "Detected in diagnostic assays as a marker of infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Reported to be glycosylated, influencing immunogenicity.", "mechanism": "Used in immunoassays for detection of infection.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated; glycosylation modulates S protein binding.", "mechanism": "Host receptor for SARS-CoV-2 S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG is N-glycosylated; glycosylation affects detection and effector function.", "mechanism": "Seroconversion marker; detected in serological assays.", "protein": "IgG antibody", "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgM is N-glycosylated; glycosylation impacts detection.", "mechanism": "Early immune response marker; detected in rapid tests.", "protein": "IgM antibody", "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "CRP is glycosylated; glycosylation may affect function and detection.", "mechanism": "Inflammatory marker elevated in severe cases.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry via ACE2 in SARS-CoV.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry via DPP4 in MERS-CoV.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300484" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Glycosylation affects immunogenicity and detection.", "mechanism": "Used in immunoassays for SARS diagnosis.", "protein": "Nucleocapsid (N) protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "K9N4V7" }, "relationship_type": "biomarker", "source_pmcid": "PMC9300484" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and immune recognition.", "mechanism": "Target of neutralizing antibodies and vaccines.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assay sensitivity.", "mechanism": "Major antigen detected in diagnostic assays.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Surface glycoprotein involved in viral entry and spread.", "protein": "Hemagglutinin-esterase (HE)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein function.", "mechanism": "Structural component required for viral assembly and release.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence virion structure.", "mechanism": "Essential for virion assembly and morphogenesis.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of both receptor and viral S protein modulates interaction.", "mechanism": "Alternative receptor for SARS-CoV-2 entry (low affinity).", "protein": "CD209L (L-SIGN)", "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of CD147 and S protein affects binding.", "mechanism": "Alternative receptor for SARS-CoV-2 entry (low affinity).", "protein": "CD147 (Basigin)", "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "medium", "disease": "Vaccine escape variants of COVID-19", "glycan_involvement": "Altered glycosylation patterns may contribute to immune evasion.", "mechanism": "Mutations in S glycoprotein can mediate escape from neutralizing antibodies.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9300555" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation can affect antibody binding sites.", "mechanism": "Monoclonal antibody therapies (e.g., bamlanivimab, casirivimab) target S protein.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9300555" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of S protein is critical for receptor binding and immune evasion.", "mechanism": "Mediates viral entry via binding to ACE2 and fusion with host membrane.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and antibody recognition.", "mechanism": "S protein is targeted in immunoassays for detection of SARS-CoV-2 antibodies.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "N protein is used in RT-PCR and immunoassays for viral detection.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates S protein binding affinity.", "mechanism": "Host receptor for S protein, mediates viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334984" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycan involvement described.", "mechanism": "Primes S protein for membrane fusion and entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation influences host receptor binding.", "mechanism": "S protein mediates entry via ACE2 in SARS-CoV.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "MERS", "glycan_involvement": "Glycosylation affects receptor specificity.", "mechanism": "S protein mediates entry via DPP4 in MERS-CoV.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgG is a glycoprotein; glycosylation affects effector function.", "mechanism": "IgG against S and N proteins used to detect prior infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IgM is a glycoprotein; glycosylation affects immune response.", "mechanism": "IgM against S and N proteins indicates recent infection.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "biomarker", "source_pmcid": "PMC9334984" }, { "confidence": "medium", "disease": "Acute Respiratory Distress Syndrome (ARDS)", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenicity.", "mechanism": "Viral entry and replication in lung cells mediated by S protein can lead to ARDS.", "protein": "Spike protein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334984" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells, enabling infection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and detection sensitivity.", "mechanism": "Targeted in antigen-based diagnostic tests for SARS-CoV-2 detection.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9334987" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycans influence immunogenicity and vaccine design.", "mechanism": "Target for vaccines and neutralizing antibodies to block viral entry.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion assembly and immune evasion.", "mechanism": "Essential for viral assembly and defines envelope structure.", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate protein function and virus morphogenesis.", "mechanism": "Involved in virus assembly and release.", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates Spike binding affinity.", "mechanism": "Host receptor for Spike protein, mediating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Similar glycosylation patterns as SARS-CoV-2 S protein.", "mechanism": "Mediates entry of SARS-CoV into host cells via ACE2.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates entry of MERS-CoV into host cells (via DPP4, not ACE2).", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "Used as antigen in some diagnostic assays.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9334987" }, { "confidence": "medium", "disease": "Pneumonia", "glycan_involvement": "Glycosylation modulates immune recognition and pathogenesis.", "mechanism": "Initiates infection leading to pneumonia-like symptoms.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334987" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation affects receptor binding and immune evasion.", "mechanism": "S protein mediates viral entry via ACE2 and NRP1 binding; detected by aptasensors for diagnosis.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no direct glycan involvement.", "mechanism": "N protein packages viral RNA and is abundant; detected by aptasensors for early diagnosis.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates RBD conformation and immune recognition.", "mechanism": "RBD binds ACE2 for viral entry; aptasensors detect RBD for specific diagnosis.", "protein": "Spike glycoprotein RBD", "relationship_type": "biomarker", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Glycosylation affects receptor binding and antigenicity.", "mechanism": "S protein is a key determinant of host tropism and pathogenicity; detected by aptasensors.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "SARS", "glycan_involvement": "Not glycosylated.", "mechanism": "N protein is highly expressed and used for sensitive detection via aptamers.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9334990" }, { "confidence": "medium", "disease": "Multiple organ dysfunction syndrome", "glycan_involvement": "Glycosylation enables immune evasion and tissue tropism.", "mechanism": "S protein enables viral entry into multiple tissues expressing ACE2/NRP1, leading to systemic inflammation.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9334990" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation modulates S protein binding.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2 S protein; tissue distribution determines disease severity.", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC9334990" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "NRP1 glycosylation may affect S protein interaction.", "mechanism": "NRP1 facilitates SARS-CoV-2 entry in addition to ACE2.", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "causal", "source_pmcid": "PMC9334990" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Indirect; S protein glycosylation may affect protease accessibility.", "mechanism": "TMPRSS2 cleaves S protein, activating it for membrane fusion and entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation shields epitopes, affecting neutralization.", "mechanism": "S protein is targeted by aptamers and antibodies for therapeutic and diagnostic purposes.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9334990" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry via ACE2 binding; key determinant of infectivity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation required for stability and function.", "mechanism": "Elevated in response to inflammation; correlates with disease severity.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer is a glycosylated fragment of fibrin; glycosylation affects clearance.", "mechanism": "Elevated D-dimer indicates coagulation activation and predicts mortality.", "protein": "D-dimer (Fibrin degradation product)", "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "IL-6 is glycosylated, which affects secretion and receptor binding.", "mechanism": "Upregulated in cytokine storm; drives inflammation and ARDS.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9335015" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Reported to be glycosylated; glycosylation may affect immunogenicity.", "mechanism": "Detected in diagnostic assays; indicates viral presence.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "medium", "disease": "Myocardial injury", "glycan_involvement": "Troponin is glycosylated; glycosylation may affect stability.", "mechanism": "Elevated in COVID-19 patients with cardiac involvement.", "protein": "Cardiac troponin", "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "LDH is glycosylated; glycosylation may affect serum half-life.", "mechanism": "Elevated in severe cases; reflects tissue damage and ARDS.", "protein": "Lactate dehydrogenase (LDH)", "protein_enriched": { "function": "Possible role in sperm motility", "gene_name": "Ldhc", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G85944LA" ], "uniprot_id": "P00342" }, "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Immunoglobulins are N-glycosylated; glycosylation modulates effector function.", "mechanism": "Seroconversion indicates infection; used in diagnostics.", "protein": "IgG/IgM antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated; glycosylation modulates spike binding affinity.", "mechanism": "Host cell entry receptor for SARS-CoV-2 spike protein.", "protein": "ACE2 receptor", "relationship_type": "causal", "source_pmcid": "PMC9335015" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Sialic acid residues on host glycoproteins interact with viral spike.", "mechanism": "Host cell surface sialylated glycoproteins may enhance viral attachment.", "protein": "Sialic acid-binding glycoproteins", "relationship_type": "facilitative", "source_pmcid": "PMC9335015" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation modulates immune recognition and receptor binding.", "mechanism": "Targeted by vaccines and antiviral drugs to block viral entry.", "protein": "Hemagglutinin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Glycosylation affects enzymatic activity and drug sensitivity.", "mechanism": "Targeted by neuraminidase inhibitors to prevent viral release.", "protein": "Neuraminidase", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Dense N-glycosylation shields epitopes from immune detection.", "mechanism": "Targeted by entry inhibitors and neutralizing antibodies.", "protein": "HIV-1 gp120", "protein_enriched": { "function": "Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically c", "gene_name": "env", "glycan_count": 0, "glycosylation_sites_count": 29, "glytoucan_ids": [], "uniprot_id": "P04578" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation modulates fusion and immune evasion.", "mechanism": "Targeted by fusion inhibitors (e.g., enfuvirtide).", "protein": "HIV-1 gp41", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and affect ACE2 binding.", "mechanism": "Targeted by vaccines and antiviral drugs to block viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Targeted by neutralizing antibodies and entry inhibitors.", "protein": "Dengue virus Envelope protein (E)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation shields E2 from immune recognition.", "mechanism": "Targeted by entry inhibitors and neutralizing antibodies.", "protein": "Hepatitis C virus E2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "medium", "disease": "Respiratory Syncytial Virus Infection", "glycan_involvement": "N-glycosylation affects fusion activity and immune evasion.", "mechanism": "Targeted by fusion inhibitors and neutralizing antibodies.", "protein": "Respiratory Syncytial Virus F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "medium", "disease": "Herpes Simplex Virus Infection", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "Targeted by entry inhibitors and neutralizing antibodies.", "protein": "Herpes Simplex Virus gD", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "low", "disease": "Spring Viremia of Carp", "glycan_involvement": "Glycoprotein gene expression is suppressed by antiviral agents.", "mechanism": "Targeted by antiviral compounds to inhibit viral entry.", "protein": "Spring Viremia of Carp Virus Glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9337989" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347297" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates S protein binding and viral infectivity.", "mechanism": "Host receptor for SARS-CoV-2 S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protease activity and localization.", "mechanism": "Primes S protein for fusion after ACE2 binding.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "Lung cancer (LUAD, LUSC)", "glycan_involvement": "Aberrant glycosylation (and methylation) may regulate ACE2 expression.", "mechanism": "Overexpressed in lung cancer, increasing susceptibility to SARS-CoV-2 infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9347297" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "Glycosylation affects antibody binding and receptor function.", "mechanism": "Targeted by monoclonal antibodies in HER2+ breast cancer.", "protein": "HER2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates cytokine stability and receptor interaction.", "mechanism": "Overexpressed in severe COVID-19 and lung cancer, contributing to cytokine storm and ARDS.", "protein": "CXCL10 (IP-10)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "Leukemia", "glycan_involvement": "S protein glycosylation may affect immune evasion in immunocompromised hosts.", "mechanism": "Leukemia patients' immune cells express ACE2, making them susceptible to persistent SARS-CoV-2 infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates antibody effector function.", "mechanism": "Anti-SARS-CoV-2 IgG correlates with survival; impaired in some HIV+ patients.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "Lung cancer (LUAD, LUSC)", "glycan_involvement": "Glycosylation may affect protease function.", "mechanism": "Co-expressed with ACE2 and TMPRSS2, facilitating SARS-CoV-2 entry in smokers and cancer patients.", "protein": "TMPRSS4", "protein_enriched": { "function": "Regulatory light chain of myosin. Does not bind calcium", "gene_name": "MYL3", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08590" }, "relationship_type": "causal/biomarker", "source_pmcid": "PMC9347297" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan structures modulate ligand binding.", "mechanism": "Facilitates SARS-CoV-2 entry as a co-receptor.", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9347297" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Mediates viral entry by binding to ACE2 and facilitating membrane fusion.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immunogenicity and antibody accessibility.", "mechanism": "Target for neutralizing antibodies and vaccines.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 modulates S protein binding affinity.", "mechanism": "Host receptor for S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not directly glycosylated, but acts on glycoprotein substrate.", "mechanism": "Primes S protein for membrane fusion; inhibition blocks viral entry.", "protein": "TMPRSS2", "protein_enriched": { "function": "Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for t", "gene_name": "TMPRSS2", "glycan_count": 10, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G00912UN", "G04657PL", "G06356OH", "G20210JR", "G22768VO", "G27058EU", "G44215PV", "G80920RR", "G83460ZZ", "G84452RH" ], "uniprot_id": "O15393" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9347366" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect virion assembly and immune evasion.", "mechanism": "Essential for viral assembly and budding.", "protein": "Membrane protein (M)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347366" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may modulate function.", "mechanism": "Involved in virus assembly and pathogenesis.", "protein": "Envelope protein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; included for diagnostic relevance.", "mechanism": "Used as a diagnostic marker in RT-PCR and serology.", "protein": "Nucleocapsid protein (N)", "protein_enriched": { "function": "The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny v", "gene_name": "rep", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0C6X9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9347366" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Sialylation of host glycoproteins facilitates viral binding.", "mechanism": "Serve as potential attachment factors for viral entry.", "protein": "Sialic acid-containing glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "Cytokine Release Syndrome (CRS)", "glycan_involvement": "Glycosylation modulates receptor function and antibody binding.", "mechanism": "Targeted by tocilizumab to block IL-6 signaling in severe COVID-19.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9347366" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect antibody binding and T-cell interactions.", "mechanism": "Targeted by itolizumab to modulate T-cell activation and cytokine release.", "protein": "CD6", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9347366" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein binds to ACE2 receptor to mediate viral entry into host cells, initiating infection.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "high", "disease": "COVID-19 reinfection", "glycan_involvement": "Altered glycosylation sites in variants affect antibody recognition.", "mechanism": "Mutations and glycan changes in spike protein enable immune escape and reinfection.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation influences spike binding affinity.", "mechanism": "ACE2 acts as the host receptor for spike glycoprotein, facilitating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "IgG antibodies neutralize spike glycoprotein, preventing infection.", "protein": "Antibody (IgG)", "relationship_type": "protective", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "COVID-19 reinfection", "glycan_involvement": "Glycosylation affects antigen recognition and B cell activation.", "mechanism": "Memory B cells produce antibodies upon re-exposure, reducing severity of reinfection.", "protein": "Memory B cell receptor", "relationship_type": "protective", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates TCR stability and antigen recognition.", "mechanism": "T cell receptors recognize viral antigens and mediate cellular immunity.", "protein": "T cell receptor", "relationship_type": "protective", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "Atypical pneumonia", "glycan_involvement": "Glycosylation shields spike from immune detection, promoting lung infection.", "mechanism": "Spike-mediated infection of alveolar cells leads to pneumonia.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "Similar glycosylation patterns as SARS-CoV-2.", "mechanism": "Spike protein of SARS-CoV-1 binds ACE2, causing SARS.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "MERS", "glycan_involvement": "Glycosylation modulates receptor binding and immune escape.", "mechanism": "Spike protein of MERS-CoV binds DPP4, causing MERS.", "protein": "Spike glycoprotein (S protein)", "relationship_type": "causal", "source_pmcid": "PMC9347458" }, { "confidence": "medium", "disease": "COVID-19 reinfection", "glycan_involvement": "Fc glycosylation affects antibody half-life and function.", "mechanism": "Antibody levels provide temporary protection against reinfection.", "protein": "Antibody (IgG)", "relationship_type": "protective", "source_pmcid": "PMC9347458" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Mediates viral entry into host cells via ACE2 binding.", "protein": "Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but acts on glycoprotein precursors.", "mechanism": "Essential for viral polyprotein cleavage and replication.", "protein": "3-Chymotrypsin-like protease (3CLP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but processes viral glycoproteins.", "mechanism": "Cleaves viral polyproteins and antagonizes host immune response.", "protein": "Papain-like protease (PLP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Processes glycosylated spike protein in endosomes.", "mechanism": "Host protease required for spike protein activation and viral entry.", "protein": "Cathepsin L", "protein_enriched": { "function": "Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone r", "gene_name": "CTSL", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G06110VR", "G06356OH", "G14669DU", "G22310AV", "G28681TP", "G31665QC", "G31852PQ", "G37881RL", "G39188ZX", "G41247ZX", "G43089EG", "G47518TP", "G48414YA", "G49589RB", "G50282JC", "G52527GH", "G62765YT", "G71784JC", "G75983OB", "G80920RR", "G92050GC", "G92275SC", "G96091TT" ], "uniprot_id": "P07711" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation, but acts on viral RNA associated with glycoprotein complexes.", "mechanism": "Methylates viral RNA cap to evade host immunity.", "protein": "2-O-methyltransferase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation.", "mechanism": "Processes viral RNA to evade host immune detection.", "protein": "EndoRNAse", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "No direct glycosylation.", "mechanism": "Unwinds viral RNA during replication.", "protein": "Helicase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "N-glycans modulate antigenicity and immune evasion.", "mechanism": "Surface glycoprotein used for diagnosis and vaccine targeting.", "protein": "Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Acts on glycosylated spike protein.", "mechanism": "Facilitates viral entry by cleaving spike protein in endolysosomes.", "protein": "Cathepsin L", "protein_enriched": { "function": "Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone r", "gene_name": "CTSL", "glycan_count": 25, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO", "G02815KT", "G06110VR", "G06356OH", "G14669DU", "G22310AV", "G28681TP", "G31665QC", "G31852PQ", "G37881RL", "G39188ZX", "G41247ZX", "G43089EG", "G47518TP", "G48414YA", "G49589RB", "G50282JC", "G52527GH", "G62765YT", "G71784JC", "G75983OB", "G80920RR", "G92050GC", "G92275SC", "G96091TT" ], "uniprot_id": "P07711" }, "relationship_type": "causal", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "SARS-CoV-2 infection", "glycan_involvement": "Processes glycoprotein precursors.", "mechanism": "Processes viral polyproteins required for replication.", "protein": "3-Chymotrypsin-like protease (3CLP)", "relationship_type": "causal", "source_pmcid": "PMC9349892" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect stability and serum half-life.", "mechanism": "Elevated serum AST indicates hepatocyte damage due to membrane leakage.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9359327" }, { "confidence": "high", "disease": "Acute liver injury", "glycan_involvement": "ALT is a glycoprotein; glycosylation may influence secretion.", "mechanism": "ALT release into serum reflects hepatocyte injury.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9359327" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Collagen is glycosylated (hydroxylysine-linked sugars); glycosylation affects fibril formation.", "mechanism": "Excessive deposition of type I collagen by activated hepatic stellate cells drives fibrosis.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9359327" }, { "confidence": "high", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation modulates collagen fiber assembly and stability.", "mechanism": "Type III collagen accumulates in fibrotic liver, contributing to ECM expansion.", "protein": "Type III Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9359327" }, { "confidence": "medium", "disease": "Oxidative stress", "glycan_involvement": "Catalase is glycosylated; glycosylation may affect enzyme stability.", "mechanism": "Catalase detoxifies hydrogen peroxide, reducing oxidative damage in liver.", "protein": "CAT", "relationship_type": "protective", "source_pmcid": "PMC9359327" }, { "confidence": "high", "disease": "Oxidative stress", "glycan_involvement": "Not a glycoprotein.", "mechanism": "GSH neutralizes ROS, protecting hepatocytes from oxidative injury.", "protein": "GSH", "relationship_type": "protective", "source_pmcid": "PMC9359327" }, { "confidence": "medium", "disease": "Liver cirrhosis", "glycan_involvement": "Glycosylation influences collagen cross-linking and matrix organization.", "mechanism": "Chronic accumulation of type I collagen leads to cirrhotic scarring.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9359327" }, { "confidence": "medium", "disease": "Extracellular matrix accumulation", "glycan_involvement": "Glycosylation modulates ECM protein interactions.", "mechanism": "Increased collagen is a marker of ECM expansion in fibrosis.", "protein": "Type I Collagen", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9359327" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect serum detection.", "mechanism": "Persistently elevated AST reflects ongoing hepatocyte injury and fibrogenesis.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9359327" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may affect serum detection.", "mechanism": "ALT elevation is associated with chronic hepatocyte injury and fibrosis.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9359327" }, { "confidence": "high", "disease": "Gastric cancer", "glycan_involvement": "PD-L1 is a glycoprotein; glycosylation affects stability and detection", "mechanism": "PD-L1 expression on tumor and immune cells predicts response to anti-PD-1/PD-L1 immunotherapy", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9364699" }, { "confidence": "high", "disease": "Oesophago-gastric junction carcinoma", "glycan_involvement": "Glycosylation modulates PD-L1 function and antibody recognition", "mechanism": "PD-L1 CPS score guides immunotherapy eligibility", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9364699" }, { "confidence": "medium", "disease": "Colorectal cancer", "glycan_involvement": "Glycosylation may influence PD-L1 stability and immune evasion", "mechanism": "PD-L1 expression and MSI status predict response to checkpoint inhibitors", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9364699" }, { "confidence": "medium", "disease": "Small bowel adenocarcinoma", "glycan_involvement": "Glycosylation affects PD-L1 detection and function", "mechanism": "PD-L1 expression correlates with MSI status and tumor aggressiveness", "protein": "PD-L1 (CD274)", "relationship_type": "biomarker", "source_pmcid": "PMC9364699" }, { "confidence": "high", "disease": "Breast cancer", "glycan_involvement": "HER2 is N-glycosylated, affecting receptor function and antibody binding", "mechanism": "HER2 overexpression guides targeted therapy (trastuzumab)", "protein": "HER2 (ERBB2)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9364699" }, { "confidence": "high", "disease": "Choriocarcinoma", "glycan_involvement": "\u03b2-HCG is heavily glycosylated; glycosylation is essential for stability and bioactivity", "mechanism": "Elevated serum \u03b2-HCG is diagnostic and used for monitoring", "protein": "Beta-human chorionic gonadotropin (\u03b2-HCG)", "relationship_type": "biomarker", "source_pmcid": "PMC9364699" }, { "confidence": "high", "disease": "Myo\ufb01broblastoma, Solitary fibrous tumor, Pseudoangiomatous stromal hyperplasia (PASH)", "glycan_involvement": "CD34 is a sialomucin glycoprotein; glycosylation is critical for function and detection", "mechanism": "CD34 immunoreactivity distinguishes stromal tumors in breast pathology", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "diagnostic_marker", "source_pmcid": "PMC9364699" }, { "confidence": "medium", "disease": "Clear cell odontogenic carcinoma", "glycan_involvement": "MUC1 is highly O-glycosylated; glycosylation affects antigenicity", "mechanism": "EMA positivity helps distinguish odontogenic carcinoma from other clear cell tumors", "protein": "Epithelial membrane antigen (EMA/MUC1)", "relationship_type": "diagnostic_marker", "source_pmcid": "PMC9364699" }, { "confidence": "medium", "disease": "Gastric cancer", "glycan_involvement": "PD-1 is glycosylated, which may affect ligand binding and antibody therapy", "mechanism": "PD-1 on T cells is targeted by checkpoint inhibitors (e.g., pembrolizumab)", "protein": "PD-1 (PDCD1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9364699" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "EBV envelope glycoproteins are involved in immune recognition and autoimmunity", "mechanism": "EBV infection may trigger SLE in genetically susceptible individuals", "protein": "EBV glycoproteins (implied, not directly named)", "relationship_type": "causal/trigger", "source_pmcid": "PMC9364699" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates infectivity.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 binding.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9383864" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity and viral entry efficiency.", "mechanism": "ACE2 acts as the cellular receptor for SARS-CoV-2, facilitating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9383864" }, { "confidence": "medium", "disease": "Chronic Kidney Disease (CKD)", "glycan_involvement": "Altered host glycosylation may affect viral-host interactions.", "mechanism": "CKD patients are more susceptible to severe COVID-19 due to impaired immunity.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9383864" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Glycosylation status may modulate ACE2 function in diabetic kidneys.", "mechanism": "ACE2 expression and glycosylation may be altered in DKD, influencing susceptibility to SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9383864" }, { "confidence": "medium", "disease": "Diabetic Kidney Disease (DKD)", "glycan_involvement": "Host glycosylation changes in diabetes may affect viral entry.", "mechanism": "DKD patients have higher COVID-19 mortality, possibly due to altered glycoprotein interactions.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9383864" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation shields epitopes, modulates infectivity.", "mechanism": "Spike protein mediates viral entry via ACE2 binding.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9383882" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects receptor binding and viral entry.", "mechanism": "ACE2 is the host receptor for SARS-CoV-2.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9383882" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation modulates clot formation.", "mechanism": "Altered fibrinogen levels reflect coagulation abnormalities.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9383882" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates antibody effector functions.", "mechanism": "IgG response indicates immune activation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9383882" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycosylation affects cytokine stability and signaling.", "mechanism": "IL-6 drives hyperinflammation in severe COVID-19.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "causal", "source_pmcid": "PMC9383882" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation status changes in acute phase response.", "mechanism": "Transferrin levels reflect iron metabolism and inflammation.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9383882" }, { "confidence": "low", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation required for bioactivity.", "mechanism": "Regulates platelet production; altered in COVID-19.", "protein": "Thrombopoietin", "protein_enriched": { "function": "Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:11741539, PubMed:9230079). The Arp2/3 complex m", "gene_name": "ARPC1B", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O15143" }, "relationship_type": "causal", "source_pmcid": "PMC9383882" }, { "confidence": "low", "disease": "Hypoxemia", "glycan_involvement": "Glycosylation essential for stability and function.", "mechanism": "Stimulates erythropoiesis to counter hypoxemia.", "protein": "Erythropoietin", "relationship_type": "protective", "source_pmcid": "PMC9383882" }, { "confidence": "low", "disease": "Multi-organ failure", "glycan_involvement": "Glycosylation affects half-life and antioxidant capacity.", "mechanism": "Low albumin reflects poor prognosis in severe COVID-19.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC9383882" }, { "confidence": "low", "disease": "Sepsis", "glycan_involvement": "Glycosylation modulates complement activity.", "mechanism": "Complement activation contributes to systemic inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "causal", "source_pmcid": "PMC9383882" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycosylation of Spike is essential for receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2 on host cells.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "ACE2 glycosylation modulates Spike binding affinity.", "mechanism": "Acts as the entry receptor for SARS-CoV-2 via interaction with Spike.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "medium", "disease": "Pulmonary damage", "glycan_involvement": "Glycosylation shields Spike from immune detection.", "mechanism": "Facilitates viral entry into lung epithelial cells, leading to cytopathic effects.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "medium", "disease": "Cardiac damage", "glycan_involvement": "Glycosylation affects tissue tropism and immune response.", "mechanism": "Enables infection of cardiomyocytes via ACE2, contributing to cardiac injury.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "medium", "disease": "Pulmonary damage", "glycan_involvement": "Glycosylation may influence ACE2 localization and function.", "mechanism": "ACE2 expression in lung cells allows viral entry and subsequent tissue damage.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "medium", "disease": "Cardiac damage", "glycan_involvement": "Glycosylation status may affect susceptibility.", "mechanism": "ACE2 on cardiomyocytes mediates SARS-CoV-2 entry and cytotoxicity.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9384010" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Reduced ACE2 may alter glycosylation-dependent viral binding.", "mechanism": "Valsartan reduces ACE2 expression, limiting viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9384010" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Glycan shield impacts antibody accessibility.", "mechanism": "Target for neutralizing antibodies and entry inhibitors.", "protein": "Spike (S) glycoprotein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9384010" }, { "confidence": "high", "disease": "Acute myopericarditis", "glycan_involvement": "TnT is glycosylated, which may affect its stability and detection as a biomarker.", "mechanism": "Elevated TnT indicates myocardial injury in myopericarditis.", "protein": "Troponin T (TnT)", "relationship_type": "biomarker", "source_pmcid": "PMC9384056" }, { "confidence": "high", "disease": "Acute myopericarditis", "glycan_involvement": "CRP is N-glycosylated, influencing its plasma half-life and function.", "mechanism": "CRP elevation reflects systemic inflammation associated with myopericarditis.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9384056" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "IgG Fc glycosylation modulates effector functions and inflammation.", "mechanism": "IgG levels indicate immune response to SARS-CoV-2 or vaccination.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9384056" }, { "confidence": "low", "disease": "Acute myopericarditis", "glycan_involvement": "IgG glycosylation may influence inflammatory potential.", "mechanism": "High IgG levels post-vaccination used to exclude acute infection as etiology.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9384056" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates receptor binding.", "mechanism": "Mediates viral entry into host cells via ACE2 binding and membrane fusion.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Glycosylation affects tropism and immune evasion, enabling inner ear infection.", "mechanism": "Facilitates SARS-CoV-2 entry into inner ear cells expressing ACE2, leading to direct cytopathic effects and inflammation.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "Vestibular diseases", "glycan_involvement": "Glycosylation modulates receptor interaction and tissue targeting.", "mechanism": "Enables viral entry into vestibular tissues via ACE2, causing inflammation and ischemia.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "Tinnitus", "glycan_involvement": "Glycosylation shields S-protein from immune detection, facilitating persistence.", "mechanism": "Neuroinvasion and inflammation in auditory pathways following viral entry.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "low", "disease": "Facial palsy", "glycan_involvement": "Glycosylation may affect neurotropism.", "mechanism": "Neurotropic invasion and immune-mediated nerve damage.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which modulates S-protein binding affinity.", "mechanism": "Host receptor for S-protein, mediating viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "Hearing loss", "glycan_involvement": "Glycosylation of ACE2 influences susceptibility to viral entry.", "mechanism": "ACE2 expression in inner ear enables SARS-CoV-2 infection and subsequent tissue damage.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Contains glycosylation sites affecting virion stability.", "mechanism": "Involved in virus assembly, release, and host cell membrane permeability.", "protein": "Envelope protein (E-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein, but may interact with host glycoproteins.", "mechanism": "Essential for viral RNA packaging and replication.", "protein": "Nucleocapsid protein (N-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "medium", "disease": "Autoimmune inner ear disease (AIED)", "glycan_involvement": "Glycosylation of S-protein in vaccines may influence immunogenicity.", "mechanism": "mRNA vaccines encoding S-protein may trigger immune responses leading to AIED exacerbation.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9389503" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of Spike is critical for receptor binding and immune evasion.", "mechanism": "Spike glycoprotein mediates viral entry by binding to ACE2 on host cells.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9395237" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 may modulate Spike binding affinity.", "mechanism": "ACE2 acts as the host receptor for SARS-CoV-2 Spike glycoprotein.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9395237" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation sites on Spike are targeted by neutralizing antibodies and inhibitors.", "mechanism": "Blocking Spike-ACE2 interaction prevents viral entry.", "protein": "SARS-CoV-2 Spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395237" }, { "confidence": "high", "disease": "Solid tumors (cancer)", "glycan_involvement": "Tumor-specific glycan structures distinguish cancer cells from normal cells.", "mechanism": "Abnormal glycosylation patterns on tumor glycoproteins serve as targets for CAR T cell therapy.", "protein": "Cancer cell surface glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395237" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "3CL pro is a viral glycoprotein; glycosylation may affect folding and function.", "mechanism": "Essential for viral polyprotein processing; inhibition blocks viral replication.", "protein": "3CL pro (Main Protease, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Nsp15 is a viral glycoprotein; glycosylation may influence stability and activity.", "mechanism": "Involved in viral RNA processing and evasion of host immune response; inhibition impairs replication.", "protein": "Nsp15 (Endoribonuclease)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential impact on glycoprotein conformation and inhibitor binding.", "mechanism": "Phytochemicals (rutin, quercetin, catechin gallate, rhamnetin, stigmasterol, campesterol) bind and inhibit protease activity.", "protein": "3CL pro (Main Protease, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential impact on glycoprotein conformation and inhibitor binding.", "mechanism": "Phytochemicals (especially rutin) bind and inhibit endoribonuclease activity.", "protein": "Nsp15 (Endoribonuclease)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect accessibility of active site.", "mechanism": "Rutin forms strong H-bonds with key active site residues (HIS41, CYS145), inhibiting protease.", "protein": "3CL pro (Main Protease, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect accessibility of active site.", "mechanism": "Rutin forms strong H-bonds with key residue (THR341), inhibiting endoribonuclease.", "protein": "Nsp15 (Endoribonuclease)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate inhibitor binding.", "mechanism": "Stigmasterol and campesterol also inhibit protease by binding active site.", "protein": "3CL pro (Main Protease, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate inhibitor binding.", "mechanism": "Stigmasterol and campesterol inhibit endoribonuclease by binding active site.", "protein": "Nsp15 (Endoribonuclease)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence inhibitor access.", "mechanism": "Quercetin, catechin gallate, rhamnetin show moderate inhibition via active site binding.", "protein": "3CL pro (Main Protease, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may influence inhibitor access.", "mechanism": "Quercetin, catechin gallate, rhamnetin show moderate inhibition via active site binding.", "protein": "Nsp15 (Endoribonuclease)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9395807" }, { "confidence": "high", "disease": "Juvenile idiopathic arthritis", "glycan_involvement": "Glycosylation affects TNF receptor binding and antibody efficacy.", "mechanism": "Anti-TNF biotherapies reduce inflammation and disease progression.", "protein": "TNF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Auto-inflammatory diseases", "glycan_involvement": "Glycosylation modulates IL-1 receptor interactions.", "mechanism": "Anti-IL-1 therapies (e.g., Anakinra) block IL-1 signaling to reduce inflammation.", "protein": "IL-1", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Juvenile idiopathic arthritis", "glycan_involvement": "Glycosylation influences IL-6 receptor binding and antibody function.", "mechanism": "Anti-IL-6 therapy (e.g., Tocilizumab) inhibits IL-6-mediated inflammation.", "protein": "IL-6", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to tri", "gene_name": "Il6", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08505" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PD-1 glycosylation affects ligand binding and antibody recognition.", "mechanism": "Anti-PD-1 antibodies (e.g., nivolumab, pembrolizumab) block immune checkpoint to enhance anti-tumor immunity.", "protein": "PD-1", "protein_enriched": { "function": "Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:37208329). Delivers inhibitory signals upo", "gene_name": "PDCD1", "glycan_count": 2, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G81315DD", "G42466VF" ], "uniprot_id": "Q15116" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "PD-L1 glycosylation modulates immune evasion and antibody binding.", "mechanism": "Anti-PD-L1 antibodies (e.g., atezolizumab) block immune suppression in tumors.", "protein": "PD-L1", "protein_enriched": { "function": "Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1,", "gene_name": "CD274", "glycan_count": 1, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G31852PQ" ], "uniprot_id": "Q9NZQ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "CTLA-4 glycosylation regulates surface expression and immune function.", "mechanism": "Anti-CTLA-4 antibody (ipilimumab) enhances T cell activation against tumors.", "protein": "CTLA-4", "protein_enriched": { "function": "Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of thei", "gene_name": "CTLA4", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P16410" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Retinal diseases", "glycan_involvement": "VEGF glycosylation affects receptor binding and drug targeting.", "mechanism": "Anti-VEGF agents inhibit pathological angiogenesis in the retina.", "protein": "VEGF", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9421640" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "Antibody glycosylation may influence ocular tissue interactions.", "mechanism": "Repeated intravitreal injections associated with increased risk of glaucoma.", "protein": "Bevacizumab", "relationship_type": "causal", "source_pmcid": "PMC9421640" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "Fab fragment glycosylation may affect intraocular pressure.", "mechanism": "Repeated intravitreal injections associated with increased risk of glaucoma.", "protein": "Ranibizumab", "relationship_type": "causal", "source_pmcid": "PMC9421640" }, { "confidence": "medium", "disease": "Glaucoma", "glycan_involvement": "Fusion protein glycosylation may impact ocular pharmacokinetics.", "mechanism": "Repeated intravitreal injections associated with increased risk of glaucoma (lower than other agents).", "protein": "Aflibercept", "relationship_type": "causal", "source_pmcid": "PMC9421640" }, { "confidence": "high", "disease": "Influenza", "glycan_involvement": "Neuraminidase is a glycoprotein essential for viral egress; glycosylation affects its function.", "mechanism": "Chebulagic acid and chebulinic acid from Terminalia chebula inhibit neuraminidase, blocking viral release.", "protein": "Viral neuraminidase glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "S protein is heavily glycosylated, mediating host cell attachment.", "mechanism": "Phytochemicals (e.g., withanone, ursolic acid) block S protein-ACE2 interaction, inhibiting viral entry.", "protein": "Viral spike glycoprotein (S protein)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "high", "disease": "Herpes simplex virus infection (HSV-1/2)", "glycan_involvement": "HSV entry depends on glycoprotein-mediated binding to host cell receptors.", "mechanism": "T. chebula and Moringa extracts inhibit HSV glycoprotein-mediated attachment and entry.", "protein": "HSV glycoproteins", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "ACE2 is N-glycosylated, which modulates S protein binding.", "mechanism": "Withanone from Withania somnifera binds ACE2, reducing S protein interaction.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "medium", "disease": "Influenza", "glycan_involvement": "HA protein is a viral glycoprotein binding sialic acid on host glycoproteins.", "mechanism": "Tulsi terpenoids and polyphenols block viral HA protein binding, preventing entry.", "protein": "Hyaluronic acid binding protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "medium", "disease": "Hepatitis B", "glycan_involvement": "HBsAg is a glycoprotein; glycosylation is critical for infectivity.", "mechanism": "Moringa leaf extract reduces HBV DNA and HBsAg expression.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "gp120 is heavily glycosylated; glycans shield it from immune recognition.", "mechanism": "Plant-derived compounds (e.g., ajoene from garlic) inhibit gp120-mediated entry.", "protein": "HIV gp120", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "medium", "disease": "Dengue", "glycan_involvement": "Envelope glycoproteins are glycosylated, mediating host interaction.", "mechanism": "Neem extracts interfere with viral envelope glycoprotein-mediated entry and replication.", "protein": "Viral envelope glycoproteins (general)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "NSP15 is not a glycoprotein but interacts with viral RNA; glycosylation not directly involved.", "mechanism": "Withanoside X and quercetin glucoside from W. somnifera bind NSP15, inhibiting viral replication.", "protein": "SARS-CoV-2 NSP15", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "low", "disease": "Poliovirus infection", "glycan_involvement": "Pirin is a host glycoprotein; glycosylation may affect function.", "mechanism": "Quercetin from Moringa inhibits poliovirus by reducing pirin protein expression.", "protein": "Pirin", "protein_enriched": { "function": "Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid mat", "gene_name": "PIR", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O00625" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9422945" }, { "confidence": "high", "disease": "Multiple Myeloma", "glycan_involvement": "BCMA glycosylation may affect antigen recognition and CAR-T efficacy.", "mechanism": "Targeted by CAR-T cells for elimination of malignant plasma cells.", "protein": "BCMA", "protein_enriched": { "function": "Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane (PubMed:36264797). Catalyzes insertion of proteins with alpha-helical transmembrane regions, s", "gene_name": "MTCH1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q9NZJ7" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Primary Mediastinal Large B-cell Lymphoma (PMBCL)", "glycan_involvement": "Glycosylation may modulate CD58-mediated cell adhesion and immune recognition.", "mechanism": "Mutated CD58 associated with poor survival in PMBCL.", "protein": "CD58", "protein_enriched": { "function": "Ligand of the T-lymphocyte CD2 glycoprotein. This interaction is important in mediating thymocyte interactions with thymic epithelial cells, antigen-independent and -dependent interactions of T-lympho", "gene_name": "CD58", "glycan_count": 8, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G36921VW", "G10773YW", "G11738SE", "G62765YT", "G80920RR", "G93718GY", "G49108TO", "G34989PA" ], "uniprot_id": "P19256" }, "relationship_type": "biomarker", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Bone Marrow Failure Syndromes", "glycan_involvement": "Sialylation of CD34 regulates stem cell homing and survival.", "mechanism": "Loss of CD34+ cells observed in hnRNP K-driven bone marrow failure.", "protein": "CD34", "protein_enriched": { "function": "Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold fo", "gene_name": "CD34", "glycan_count": 71, "glycosylation_sites_count": 9, "glytoucan_ids": [ "G57317CE", "G73004SD", "G00273SJ", "G00912UN", "G01650EU", "G02815KT", "G04657PL", "G05049YU", "G06247RL", "G08918WF", "G10486CT", "G10819WX", "G10846ZT", "G11314AS", "G13131HA", "G14972EH", "G18647XP", "G20528HD", "G23863VK", "G27058EU", "G27126ED", "G27947YN", "G28541PG", "G29299MO", "G30740WO", "G31852PQ", "G35541EV", "G37399XV", "G39446WN", "G40574BA", "G40834TG", "G40926MX", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G45395BF", "G46691LC", "G47644PP", "G49755GI", "G50856PC", "G57776ZS", "G57776ZU", "G59626AS", "G59924QI", "G60834IK", "G63041LO", "G65184UU", "G68490OW", "G69521XL", "G70441OD", "G70619PT", "G72747WU", "G72790NZ", "G75568BH", "G75983OB", "G79666IR", "G80075MS", "G83646BJ", "G84452RH", "G85269DF", "G86880BF", "G87123QX", "G87661QW", "G90659AW", "G92135MA", "G92406TI", "G95865ZB", "G96091TT", "G98611JV", "G99668VU" ], "uniprot_id": "P28906" }, "relationship_type": "biomarker", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Primary Mediastinal Large B-cell Lymphoma (PMBCL)", "glycan_involvement": "Glycosylation of B2M affects MHC class I stability and antigen presentation.", "mechanism": "Recurrent B2M mutations drive immune escape in PMBCL.", "protein": "B2M", "relationship_type": "causal", "source_pmcid": "PMC9429973" }, { "confidence": "medium", "disease": "Primary Mediastinal Large B-cell Lymphoma (PMBCL)", "glycan_involvement": "Potential O-glycosylation may regulate SOCS1 stability and signaling.", "mechanism": "SOCS1 mutations are frequent drivers in PMBCL.", "protein": "SOCS1", "protein_enriched": { "function": "Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:32499645, PubMed", "gene_name": "SOCS1", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "O15524" }, "relationship_type": "causal", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Bone Marrow Failure Syndromes", "glycan_involvement": "Glycosylation may affect hnRNP K localization and RNA processing.", "mechanism": "Overexpression causes hyper-nucleoli, ribosome gain-of-function, and stem cell exhaustion.", "protein": "hnRNP K", "protein_enriched": { "function": "One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich seq", "gene_name": "HNRNPK", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G85554PZ" ], "uniprot_id": "P61978" }, "relationship_type": "causal", "source_pmcid": "PMC9429973" }, { "confidence": "medium", "disease": "Bone Marrow Failure Syndromes", "glycan_involvement": "N-glycosylation modulates nucleolin function in ribosome biogenesis.", "mechanism": "Upregulated in hnRNP K-driven nucleolar stress and ribosomopathy.", "protein": "NCL (Nucleolin)", "relationship_type": "biomarker", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "T-cell Acute Lymphoblastic Leukemia (T-ALL)", "glycan_involvement": "N-glycosylation may regulate LCK membrane localization and signaling.", "mechanism": "Deubiquitination by USP11/USP7 controls LCK activity and therapy response.", "protein": "LCK", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Relapsed/Refractory T-cell Malignancies", "glycan_involvement": "Glycosylation affects CD7 antigenicity and CAR-T targeting.", "mechanism": "CD7 knockout CAR-T cells used for targeted therapy.", "protein": "CD7", "protein_enriched": { "function": "Transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors (PubMed:7506726). Plays a costimulatory role in T-cell activation upon binding to its ligand K12/SECT", "gene_name": "CD7", "glycan_count": 5, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G04657PL", "G27058EU", "G31852PQ", "G45395BF", "G90659AW" ], "uniprot_id": "P09564" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "Drug-resistant Leukemia", "glycan_involvement": "Glycosylation may influence BCL2 stability and apoptosis regulation.", "mechanism": "BCL2 inhibition re-sensitizes resistant ALL cells to chemotherapy.", "protein": "BCL2", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9429973" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation shields epitopes and modulates immune recognition.", "mechanism": "Spike protein mediates viral entry and is target for neutralizing antibodies and vaccines.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "O-glycosylation reported; may affect immune recognition.", "mechanism": "N protein is critical for viral replication and assembly; used in diagnostics.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation modulates receptor binding and immune evasion.", "mechanism": "E2 mediates viral entry by binding to host CD81.", "protein": "HCV Envelope glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "Glycosylation may affect E2 binding.", "mechanism": "Host receptor for HCV E2; blocking CD81 can inhibit HCV entry.", "protein": "CD81", "protein_enriched": { "function": "Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking an", "gene_name": "CD81", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P60033" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "Dengue", "glycan_involvement": "N-glycosylation required for secretion and immune modulation.", "mechanism": "NS1 is secreted and detected in blood during acute infection.", "protein": "Dengue virus NS1", "protein_enriched": { "function": "Involved in DNA nucleotide excision repair (NER). Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Requi", "gene_name": "XPA", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P23025" }, "relationship_type": "biomarker", "source_pmcid": "PMC9442589" }, { "confidence": "medium", "disease": "Japanese encephalitis", "glycan_involvement": "N-glycosylation affects neuroinvasiveness and immune evasion.", "mechanism": "E protein mediates viral entry and fusion.", "protein": "Japanese encephalitis virus E protein", "relationship_type": "causal", "source_pmcid": "PMC9442589" }, { "confidence": "medium", "disease": "Respiratory Syncytial Virus infection", "glycan_involvement": "N-glycosylation modulates antigenicity.", "mechanism": "F protein mediates membrane fusion; target for neutralizing antibodies.", "protein": "RSV F protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9442589" }, { "confidence": "medium", "disease": "Chandipura virus encephalitis", "glycan_involvement": "Predicted N-glycosylation sites; may affect immunogenicity.", "mechanism": "G protein is the main viral envelope glycoprotein and target for neutralizing antibodies.", "protein": "Chandipura virus G protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation required for secretion and antigenicity.", "mechanism": "HBsAg is used for diagnosis and monitoring of infection.", "protein": "Hepatitis B surface antigen (HBsAg)", "relationship_type": "biomarker", "source_pmcid": "PMC9442589" }, { "confidence": "medium", "disease": "Acute liver failure", "glycan_involvement": "Can be glycosylated; glycosylation may affect secretion and immune activity.", "mechanism": "Elevated HMGB1 is a poor prognostic marker in acute liver failure.", "protein": "High mobility group box 1 protein (HMGB1)", "relationship_type": "biomarker", "source_pmcid": "PMC9442589" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Spike heavily glycosylated; glycan shield modulates immune evasion and receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry via ACE2 receptor, initiating infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects Spike binding affinity and tissue tropism.", "mechanism": "ACE2 acts as entry receptor for SARS-CoV-2, facilitating infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "medium", "disease": "Sensorineural hearing loss (SNHL)", "glycan_involvement": "Spike glycosylation may influence tissue tropism and immune response.", "mechanism": "Viral infection may damage cochlear/vestibular tissues via direct invasion or immune-mediated injury.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects stability and function.", "mechanism": "Elevated CRP indicates systemic inflammation in COVID-19.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9444266" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation may affect clearance.", "mechanism": "Elevated D-dimer reflects coagulopathy and thrombotic risk in COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9444266" }, { "confidence": "medium", "disease": "Autoimmune inner ear disease (AIED)", "glycan_involvement": "IgG glycosylation modulates effector function and autoimmunity.", "mechanism": "Autoimmune response may target inner ear antigens, mediated by IgG.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "medium", "disease": "Vestibular neuritis (VN)", "glycan_involvement": "Spike glycosylation may affect neuroinvasion.", "mechanism": "Viral neurotropism may cause inflammation of vestibular nerve.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "medium", "disease": "Labyrinthitis", "glycan_involvement": "Spike glycosylation may influence tissue targeting.", "mechanism": "Viral infection or immune response damages labyrinthine structures.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "medium", "disease": "Guillain-Barre Syndrome (GBS)", "glycan_involvement": "IgM glycosylation affects complement activation and immune response.", "mechanism": "Acute immune-mediated neuropathy may be triggered by viral infection and IgM response.", "protein": "Immunoglobulin M (IgM)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHM", "glycan_count": 202, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G01954BU", "G02030ZB", "G02628JF", "G03382KH", "G05724UK", "G05850WN", "G05933EN", "G06110VR", "G06356OH", "G06853GH", "G08146BT", "G08293MJ", "G10019LZ", "G10256JP", "G12580WI", "G14994KB", "G20425TQ", "G21070BH", "G22310AV", "G22625SJ", "G22674CI", "G23432EQ", "G23863VK", "G25418HZ", "G25520XG", "G26403SG", "G29651HS", "G31916IQ", "G36670VW", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G44211QA", "G44215PV", "G44953PJ", "G45495MK", "G45504EY", "G47012YE", "G47748JZ", "G48414YA", "G50757KG", "G51413EV", "G51640FO", "G55382TU", "G57818FI", "G59536GA", "G59626AS", "G61627IG", "G64527OM", "G65019XG", "G65184UU", "G65219TP", "G66163OV", "G66760KM", "G66933CM", "G67093QB", "G68318VE", "G70101JE", "G70375MX", "G70822IO", "G72667IM", "G72797UR", "G75983OB", "G79568CQ", "G80223IX", "G80735OA", "G81263BG", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85740DB", "G86500WE", "G86752LQ", "G86795LJ", "G88374WZ", "G91473PK", "G91636VS", "G92073XL", "G93683YO", "G98611JV", "G99966GV", "G02815KT", "G05642HQ", "G11115RO", "G12793SR", "G15064OQ", "G15486FH", "G39595FH", "G41044JW", "G62765YT", "G66088HZ", "G80920RR", "G82119TF", "G08520NM", "G10133VD", "G23453IV", "G25386IJ", "G31852PQ", "G33609NS", "G39446WN", "G41247ZX", "G45841FE", "G47909JD", "G55220VL", "G57317CE", "G57776ZU", "G60230HH", "G63976LA", "G66538GV", "G66676MI", "G80966KZ", "G81315DD", "G82020ZR", "G89319AW", "G93993PD", "G49108TO", "G01650EU", "G02886BB", "G09197ZW", "G09528DL", "G10339FR", "G10486CT", "G10773YW", "G11870QZ", "G15038BD", "G19379ID", "G22140GZ", "G23294PN", "G25079LO", "G25451PN", "G25987BV", "G27126ED", "G28541PG", "G29880MM", "G32392SM", "G34730YF", "G35305EF", "G37399XV", "G37442IW", "G37881RL", "G39619TI", "G43769HG", "G46687AB", "G46902YN", "G47737VJ", "G48584BU", "G49874UX", "G50045TK", "G52527GH", "G54600FO", "G56903ZB", "G59937CP", "G60033FS", "G65092SV", "G67324HN", "G67419ZC", "G70418MS", "G72291OX", "G72735IY", "G72787SB", "G72790NZ", "G72791KH", "G78059CC", "G80475RE", "G81295CK", "G82463GQ", "G84492TS", "G88725PI", "G94854LT", "G95865ZB", "G03889MY", "G12708JQ", "G17751ZM", "G21001NA", "G22340YC", "G22981GY", "G23087XI", "G26335RK", "G31936TA", "G39943KJ", "G43157UW", "G43947VZ", "G47837MS", "G48390IG", "G48712ZJ", "G55052CN", "G55811AY", "G56238AO", "G60145BJ", "G61937QU", "G75798PH", "G78261DB", "G82514MH", "G87422CM", "G87694ZF", "G87889NL", "G92129PT", "G94120DZ", "G95368PR" ], "uniprot_id": "P01871" }, "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "low", "disease": "Benign paroxysmal positional vertigo (BPPV)", "glycan_involvement": "Spike glycosylation may modulate immune response and inflammation.", "mechanism": "Indirect: COVID-19-related inflammation or trauma may lead to otoconial dislodgement.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9444266" }, { "confidence": "high", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation of MOG influences antigenicity and immune recognition.", "mechanism": "MOG acts as an autoantigen, triggering immune-mediated demyelination.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC9446916" }, { "confidence": "high", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycosylation modulates MOG's immunogenicity in EAE.", "mechanism": "MOG peptide immunization induces EAE, modeling MS pathology.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "causal", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "DUOC-01 contains glycoproteins that may mediate cell-cell interactions and signaling.", "mechanism": "DUOC-01 promotes remyelination by driving OPC differentiation into myelinating oligodendrocytes.", "protein": "DUOC-01", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Leukodystrophies", "glycan_involvement": "Glycoproteins in DUOC-01 may contribute to immunomodulation and remyelination.", "mechanism": "DUOC-01 protects against loss of function in demyelinating leukodystrophies.", "protein": "DUOC-01", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Experimental Autoimmune Encephalomyelitis (EAE)", "glycan_involvement": "Glycoprotein-mediated effects likely involved in immunomodulation.", "mechanism": "DUOC-01 injection reduces clinical scores and promotes recovery in EAE mice.", "protein": "DUOC-01", "relationship_type": "protective", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "MBP is not a glycoprotein, but its interaction with glycoproteins is relevant for myelin integrity.", "mechanism": "MBP loss indicates demyelination; its presence marks remyelination.", "protein": "Myelin Basic Protein (MBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Leukodystrophies", "glycan_involvement": "Glycosylation state may affect MOG detection and function.", "mechanism": "MOG presence/absence reflects myelin status in leukodystrophies.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycoproteins in DUOC-01 may facilitate OPC maturation.", "mechanism": "DUOC-01 enhances remyelination in LPC-induced demyelination models.", "protein": "DUOC-01", "relationship_type": "protective", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycoprotein composition may influence therapeutic efficacy.", "mechanism": "DUOC-01 may be used as a bridging therapy post-transplant in MS patients.", "protein": "DUOC-01", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9446916" }, { "confidence": "medium", "disease": "Multiple Sclerosis (MS)", "glycan_involvement": "Glycosylation affects MOG's detection and immune response.", "mechanism": "MOG is used to monitor demyelination and remyelination in MS models.", "protein": "Myelin Oligodendrocyte Glycoprotein (MOG)", "relationship_type": "biomarker", "source_pmcid": "PMC9446916" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "PLpro reverses ISGylation (a ubiquitin-like glycan modification) of host proteins.", "mechanism": "PLpro is essential for viral polyprotein processing and antagonizes host innate immunity via deubiquitination and deISGylation.", "protein": "Papain-like protease (PLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9452863" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Indirect; processes viral polyproteins that may be glycosylated.", "mechanism": "3CLpro is required for viral polyprotein cleavage, enabling viral replication.", "protein": "3-chymotrypsin-like protease (3CLpro, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9452863" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycans shield epitopes and modulate receptor binding.", "mechanism": "Spike protein mediates viral entry by binding to host cell receptors.", "protein": "Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9452863" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Removes ISG15 (a ubiquitin-like glycan) from host proteins, suppressing antiviral signaling.", "mechanism": "PLpro cleaves viral polyproteins and suppresses host immune responses.", "protein": "Papain-like protease (PLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9452863" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Activity includes deISGylation (removal of glycan-like ISG15).", "mechanism": "PLpro activity indicates active viral replication.", "protein": "Papain-like protease (PLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9452863" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Indirect; processes polyproteins that may be glycosylated.", "mechanism": "3CLpro activity reflects viral replication status.", "protein": "3-chymotrypsin-like protease (3CLpro, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9452863" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Blocks deISGylation/deubiquitination, preserving glycan modifications on host proteins.", "mechanism": "Inhibition of PLpro by flavonoids (e.g., silymarin, procyanidin) may restore host innate immunity.", "protein": "Papain-like protease (PLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9452863" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Indirect; prevents processing of viral proteins, some of which are glycosylated.", "mechanism": "Inhibition of 3CLpro by flavonoids (e.g., isonymphaeol B) may block viral replication.", "protein": "3-chymotrypsin-like protease (3CLpro, Mpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9452863" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Removes ISG15 and ubiquitin from host proteins.", "mechanism": "Host ISGylation and ubiquitination (glycan-like modifications) are protective; PLpro antagonizes this.", "protein": "Papain-like protease (PLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9452863" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans modulate immune recognition and receptor binding.", "mechanism": "Spike glycoprotein is a target for neutralizing antibodies and entry inhibitors.", "protein": "Spike protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9452863" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "Glycosylation not essential for pathogenesis or strain properties (BSE study).", "mechanism": "Misfolding of PrP^C to PrP^Sc leads to neurodegeneration.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "causal", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "Bovine Spongiform Encephalopathy (BSE)", "glycan_involvement": "Glycosylation not required for BSE strain maintenance or transmission barrier.", "mechanism": "PrP^Sc accumulation causes BSE; transmission and strain properties maintained without glycosylation.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "causal", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "Chronic Wasting Disease (CWD)", "glycan_involvement": "No direct glycan effect mentioned for codon 138; general glycoprotein context.", "mechanism": "PrP codon 138 N variant confers resistance to CWD in cervids; misfolding leads to disease.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "causal/protective", "source_pmcid": "PMC9467582" }, { "confidence": "medium", "disease": "Alzheimer\u2019s Disease", "glycan_involvement": "General glycoprotein context; not specified in this article.", "mechanism": "PrP^C implicated in pathogenesis and metabolic regulation; dysregulation contributes to neurodegeneration.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9467582" }, { "confidence": "medium", "disease": "Parkinson\u2019s Disease", "glycan_involvement": "General glycoprotein context; not specified in this article.", "mechanism": "PrP^C implicated in disease mechanisms and metabolic regulation.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "causal/therapeutic_target", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "Dementia with Lewy Bodies (DLB)", "glycan_involvement": "O-GlcNAc modification known in literature, not discussed here.", "mechanism": "Prion-like propagation of alpha-synuclein aggregates causes DLB; strain differences observed.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "Multiple System Atrophy (MSA)", "glycan_involvement": "O-GlcNAc modification known in literature, not discussed here.", "mechanism": "Distinct alpha-synuclein prion strains cause MSA; strain-specific infectivity.", "protein": "Alpha-synuclein", "protein_enriched": { "function": "Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:2828", "gene_name": "SNCA", "glycan_count": 2, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO", "G57321FI" ], "uniprot_id": "P37840" }, "relationship_type": "causal", "source_pmcid": "PMC9467582" }, { "confidence": "medium", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "Precursor glycoprotein; glycan role not specified.", "mechanism": "CSF PDYN-derived peptides differentially altered in sCJD subtypes, reflecting neuronal targeting.", "protein": "Prodynorphin (PDYN)", "protein_enriched": { "function": "Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress (By similarity)", "gene_name": "PDYN", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01213" }, "relationship_type": "biomarker", "source_pmcid": "PMC9467582" }, { "confidence": "medium", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "Precursor glycoprotein; glycan role not specified.", "mechanism": "CSF PENK-derived peptides decreased in all sCJD subtypes; associated with neurodegeneration.", "protein": "Proenkephalin (PENK)", "relationship_type": "biomarker", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "Creutzfeldt-Jakob Disease (CJD)", "glycan_involvement": "General glycoprotein context; not specified in this article.", "mechanism": "PrP^C regulates glucose metabolism; loss of function by PrP^Sc leads to neurodegeneration. PDK4 inhibition (by DCA) is neuroprotective.", "protein": "Prion protein (PrP, PrP^C, PrP^Sc)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9467582" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No direct glycosylation; function is proteolytic, not glycan-mediated.", "mechanism": "NSP5 is essential for viral replication by cleaving polyproteins; mutations alter its structure/function, affecting viral replication and pathogenesis.", "protein": "NSP5 (Main viral protease, 3CLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9472678" }, { "confidence": "medium", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No direct glycosylation; mutations affect protein structure, not glycan sites.", "mechanism": "Mutational profile of NSP5 correlates with viral evolution and potential vaccine escape.", "protein": "NSP5 (Main viral protease, 3CLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9472678" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No glycosylation involvement.", "mechanism": "NSP5 activity is required for SARS-CoV-2 replication and infection.", "protein": "NSP5 (Main viral protease, 3CLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9472678" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "No glycosylation; antigenicity is peptide-based.", "mechanism": "NSP5 B-cell and T-cell epitopes are immunogenic and non-allergenic, making NSP5 a candidate for vaccine design.", "protein": "NSP5 (Main viral protease, 3CLpro)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9472678" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates immune recognition and viral entry.", "mechanism": "S glycoprotein induces neutralizing antibodies that block virus binding and fusion to host cells.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9472678" }, { "confidence": "high", "disease": "COVID-19 (SARS-CoV-2 infection)", "glycan_involvement": "N-glycosylation shields epitopes and affects immunogenicity.", "mechanism": "S glycoprotein is the main target for current vaccines and antibody therapies.", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9472678" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "ALT is a glycoprotein; glycosylation may affect its stability and serum half-life.", "mechanism": "ALT elevation indicates hepatocellular injury during Remdesivir therapy in patients with kidney disease and COVID-19.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC9475097" }, { "confidence": "medium", "disease": "Liver Dysfunction", "glycan_involvement": "AST is a glycoprotein; glycosylation may influence its secretion and detection.", "mechanism": "AST elevation is used to monitor liver function during Remdesivir therapy in COVID-19 patients with renal impairment.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC9475097" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may modulate ALT serum levels.", "mechanism": "ALT levels are monitored to assess liver involvement in COVID-19 patients, especially those receiving Remdesivir.", "protein": "ALT (Alanine Aminotransferase)", "protein_enriched": { "function": "Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate produc", "gene_name": "FDPS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P08836" }, "relationship_type": "biomarker", "source_pmcid": "PMC9475097" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect AST function and detection.", "mechanism": "AST is used to monitor hepatic effects of COVID-19 and antiviral therapy.", "protein": "AST (Aspartate Aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC9475097" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Altered glycosylation patterns may affect protein clearance and inflammation", "mechanism": "Elevated serum levels associated with CKD progression", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9482674" }, { "confidence": "high", "disease": "Chronic Kidney Disease", "glycan_involvement": "Glycosylation status influences protein stability and renal handling", "mechanism": "Changes in transferrin levels reflect renal dysfunction", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9482674" }, { "confidence": "high", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "sCD25R is a glycoprotein; glycosylation affects its stability and detection.", "mechanism": "Elevated sCD25R reflects uncontrolled T-cell activation in MAS.", "protein": "Soluble CD25 receptor (sCD25R)", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "high", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect serum levels and clearance.", "mechanism": "Extreme hyperferritinaemia is characteristic of MAS due to inflammatory cytokine storm.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "high", "disease": "Haemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation impacts sCD25R function and measurement.", "mechanism": "Elevated sCD25R is a diagnostic criterion for HLH, reflecting T-cell activation.", "protein": "Soluble CD25 receptor (sCD25R)", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "high", "disease": "Haemophagocytic Lymphohistiocytosis (HLH)", "glycan_involvement": "Glycosylation may influence ferritin's immunogenicity and serum half-life.", "mechanism": "Hyperferritinaemia is a diagnostic marker for HLH.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "medium", "disease": "Undifferentiated Connective Tissue Disease (uCTD)", "glycan_involvement": "Immunoglobulin glycosylation modulates immune function.", "mechanism": "Polyclonal gammaglobulinaemia reflects immune activation in uCTD.", "protein": "Immunoglobulins (gammaglobulins)", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "high", "disease": "Systemic Lupus Erythematosus (SLE)", "glycan_involvement": "Glycosylation affects antibody effector function and pathogenicity.", "mechanism": "Anti-dsDNA antibodies are diagnostic for SLE; their presence indicates lupus-like disease.", "protein": "Anti-dsDNA antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "medium", "disease": "Undifferentiated Connective Tissue Disease (uCTD)", "glycan_involvement": "Glycosylation influences antibody stability and immune complex formation.", "mechanism": "Anti-Ro antibodies are associated with uCTD and other autoimmune diseases.", "protein": "Anti-Ro (SSA) antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "medium", "disease": "Undifferentiated Connective Tissue Disease (uCTD)", "glycan_involvement": "Glycosylation affects antibody function and clearance.", "mechanism": "Anti-La antibodies are associated with uCTD and Sj\u00f6gren\u2019s syndrome.", "protein": "Anti-La (SSB) antibodies", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "medium", "disease": "Macrophage Activation Syndrome (MAS)", "glycan_involvement": "Altered glycosylation may reflect immune dysregulation.", "mechanism": "Polyclonal gammaglobulinaemia observed during MAS flare.", "protein": "Immunoglobulins (gammaglobulins)", "relationship_type": "biomarker", "source_pmcid": "PMC9515801" }, { "confidence": "medium", "disease": "Glomerulonephritis", "glycan_involvement": "Antibody glycosylation modulates renal deposition and inflammation.", "mechanism": "Anti-dsDNA antibodies can deposit in glomeruli, causing immune-mediated glomerulonephritis.", "protein": "Anti-dsDNA antibodies", "relationship_type": "causal", "source_pmcid": "PMC9515801" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Glycosylation of B2GP1 affects its antigenicity and antibody binding.", "mechanism": "Anti-B2 glycoprotein 1 antibodies are diagnostic markers for APS; their presence is associated with increased risk of thrombosis.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC9515861" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation modulates B2GP1 structure and immune recognition.", "mechanism": "Autoantibodies against B2GP1 promote thrombosis by interfering with coagulation pathways.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "causal", "source_pmcid": "PMC9515861" }, { "confidence": "medium", "disease": "Thrombocytopenia", "glycan_involvement": "Glycosylation may influence antibody binding and platelet interaction.", "mechanism": "Anti-B2GP1 antibodies can lead to platelet activation and clearance.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "causal", "source_pmcid": "PMC9515861" }, { "confidence": "medium", "disease": "Pulmonary embolism", "glycan_involvement": "Glycosylation affects immunogenicity and prothrombotic activity.", "mechanism": "Anti-B2GP1 antibodies increase risk of embolic events in APS.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "causal", "source_pmcid": "PMC9515861" }, { "confidence": "medium", "disease": "Systemic lupus erythematosus (SLE)", "glycan_involvement": "Glycosylation status may affect cross-reactivity.", "mechanism": "Anti-B2GP1 antibodies may be present in SLE, indicating overlap with APS.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker", "source_pmcid": "PMC9515861" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may affect antigenicity.", "mechanism": "Anticardiolipin antibodies are diagnostic for APS and associated with thrombosis risk.", "protein": "Anticardiolipin antibody", "relationship_type": "biomarker", "source_pmcid": "PMC9515861" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Targets phospholipid-binding proteins, some of which are glycosylated.", "mechanism": "Lupus anticoagulant positivity is a diagnostic criterion for APS.", "protein": "Lupus anticoagulant", "relationship_type": "biomarker", "source_pmcid": "PMC9515861" }, { "confidence": "medium", "disease": "Catastrophic antiphospholipid syndrome (CAPS)", "glycan_involvement": "Glycosylation may influence pathogenicity and therapeutic response.", "mechanism": "Anti-B2GP1 antibodies are implicated in CAPS; rituximab may reduce antibody levels.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9515861" }, { "confidence": "low", "disease": "Optic neuritis", "glycan_involvement": "Glycosylation may affect immune complex formation.", "mechanism": "APS-related antibodies may contribute to demyelinating events such as optic neuritis.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "possible causal", "source_pmcid": "PMC9515861" }, { "confidence": "medium", "disease": "Renal involvement in APS", "glycan_involvement": "Glycosylation may modulate renal deposition and immune response.", "mechanism": "Anti-B2GP1 antibodies associated with renal manifestations (e.g., haematuria) in APS.", "protein": "Beta-2 glycoprotein 1", "protein_enriched": { "function": "Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipi", "gene_name": "APOH", "glycan_count": 141, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G00912UN", "G06247RL", "G06356OH", "G08146BT", "G08293MJ", "G08918WF", "G10486CT", "G11314AS", "G11629QQ", "G12341GU", "G14972EH", "G14994KB", "G15169WU", "G20425TQ", "G22140GZ", "G22310AV", "G22572EH", "G23863VK", "G25418HZ", "G26403SG", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G31118FR", "G31916IQ", "G33791AF", "G35029YA", "G36131WL", "G36379GD", "G38663NM", "G40574BA", "G40834TG", "G40926MX", "G41126SR", "G42358LZ", "G43223CG", "G45395BF", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G52527GH", "G55216FT", "G57317CE", "G57776ZS", "G57776ZU", "G59536GA", "G59626AS", "G62765YT", "G70232NH", "G70619PT", "G72291OX", "G72787SB", "G72797UR", "G75798PH", "G75983OB", "G77669RF", "G78644BR", "G81263BG", "G81295CK", "G82830MN", "G83555HU", "G83646BJ", "G84452RH", "G85144OK", "G86182NS", "G86500WE", "G87134ZP", "G88374WZ", "G90659AW", "G92135MA", "G92275SC", "G94470IW", "G94917XT", "G95865ZB", "G98611JV", "G00273SJ", "G02528FI", "G02886BB", "G04854VP", "G07810QS", "G26330YA", "G29545VG", "G37509XX", "G41247ZX", "G43669FQ", "G44211QA", "G44753VC", "G45526EA", "G49906RN", "G52848YE", "G60033FS", "G63040RU", "G64751KD", "G65184UU", "G75006KF", "G75568BH", "G78787DI", "G85966UN", "G86880BF", "G89827JR", "G90575OW", "G12174PW", "G57321FI", "G04657PL", "G05962QB", "G10019LZ", "G10819WX", "G10846ZT", "G11115RO", "G11911BT", "G13191RB", "G14547CB", "G18647XP", "G29299MO", "G37818NZ", "G37868ZX", "G46524LG", "G46691LC", "G46902YN", "G56518TU", "G56784JY", "G58087IP", "G63041LO", "G70888PK", "G72747WU", "G76329HL", "G77547TA", "G78790NZ", "G79666IR", "G80075MS", "G81637OR", "G85269DF", "G87123QX", "G89098OM", "G92081HT", "G99668VU", "G99679NM" ], "uniprot_id": "P02749" }, "relationship_type": "causal", "source_pmcid": "PMC9515861" }, { "confidence": "high", "disease": "Granulomatosis with Polyangiitis (GPA)", "glycan_involvement": "PR3 is a glycoprotein; glycosylation may affect antigenicity and immune recognition.", "mechanism": "PR3-ANCA autoantibodies are diagnostic and correlate with disease activity in GPA.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "biomarker", "source_pmcid": "PMC9515873" }, { "confidence": "medium", "disease": "Lumbosacral plexopathy", "glycan_involvement": "Glycosylation of PR3 may modulate immune response and pathogenicity.", "mechanism": "PR3-ANCA mediated vasculitis can cause ischemic injury to peripheral nerves, leading to plexopathy.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "causal", "source_pmcid": "PMC9515873" }, { "confidence": "medium", "disease": "Sinusitis", "glycan_involvement": "Glycosylation may affect PR3 localization and immune interactions in mucosal tissues.", "mechanism": "PR3-ANCA vasculitis can cause inflammation of sinus mucosa.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "causal", "source_pmcid": "PMC9515873" }, { "confidence": "medium", "disease": "Epistaxis", "glycan_involvement": "Glycosylation may influence PR3's interaction with vascular endothelium.", "mechanism": "PR3-ANCA vasculitis damages nasal vessels, leading to bleeding.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "causal", "source_pmcid": "PMC9515873" }, { "confidence": "low", "disease": "Acute myositis", "glycan_involvement": "Glycosylation could affect PR3's tissue distribution and immune targeting.", "mechanism": "PR3-ANCA vasculitis may rarely cause muscle inflammation.", "protein": "Proteinase 3 (PR3)", "protein_enriched": { "function": "Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:2033050, PubMed:28240246, PubMed:3198760). By cleaving and activating rec", "gene_name": "PRTN3", "glycan_count": 1, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G11870QZ" ], "uniprot_id": "P24158" }, "relationship_type": "causal", "source_pmcid": "PMC9515873" }, { "confidence": "high", "disease": "Juvenile Dermatomyositis (JDM)", "glycan_involvement": "MDA5 is a glycoprotein; glycosylation may affect antigenicity and immune recognition", "mechanism": "Anti-MDA5 autoantibodies are associated with a distinct JDM phenotype", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC9515875" }, { "confidence": "high", "disease": "Interstitial Lung Disease (ILD)", "glycan_involvement": "Glycosylation may modulate MDA5 immune complex formation and pathogenicity", "mechanism": "Anti-MDA5 positivity is linked to increased risk and severity of ILD in JDM patients", "protein": "MDA5", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9515875" }, { "confidence": "medium", "disease": "Rapidly Progressive Interstitial Lung Disease (RPILD)", "glycan_involvement": "Potential impact of glycosylation on antibody binding and disease severity", "mechanism": "Anti-MDA5 antibodies are associated with higher risk of RPILD in JDM", "protein": "MDA5", "relationship_type": "biomarker", "source_pmcid": "PMC9515875" }, { "confidence": "high", "disease": "Pneumocystis jirovecii pneumonia (PCP)", "glycan_involvement": "\u03b2-D glucan is a fungal glycan detected in host serum during infection", "mechanism": "Elevated \u03b2-D glucan in serum is a diagnostic marker for PCP infection", "protein": "\u03b2-D glucan", "relationship_type": "biomarker", "source_pmcid": "PMC9515875" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is N-glycosylated, which affects its stability and immune recognition.", "mechanism": "CRP levels increase in severe COVID-19 due to systemic inflammation and cytokine storm.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9540157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Ferritin is glycosylated, influencing its secretion and immune interactions.", "mechanism": "Ferritin levels rise in severe COVID-19 as part of the acute-phase response and hyperinflammation.", "protein": "Serum ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC9540157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates CRP's binding to immune receptors.", "mechanism": "Elevated CRP reflects and may contribute to the cytokine storm and tissue damage in severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "causal", "source_pmcid": "PMC9540157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ferritin's clearance and immune signaling.", "mechanism": "High ferritin is associated with macrophage activation and immune dysregulation in severe COVID-19.", "protein": "Serum ferritin", "relationship_type": "causal", "source_pmcid": "PMC9540157" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycan structures could be targeted to modulate CRP activity.", "mechanism": "CRP may be targeted to reduce inflammation and improve outcomes in severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9540157" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation status may influence therapeutic strategies.", "mechanism": "Lowering ferritin may help control hyperinflammation in COVID-19.", "protein": "Serum ferritin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9540157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect CRP's response to vitamin D modulation.", "mechanism": "Inverse correlation between serum vitamin D and CRP suggests vitamin D may reduce CRP-mediated inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9540157" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect ferritin's response to vitamin D modulation.", "mechanism": "Inverse correlation between serum vitamin D and ferritin suggests vitamin D may reduce ferritin-mediated inflammation.", "protein": "Serum ferritin", "relationship_type": "biomarker", "source_pmcid": "PMC9540157" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycans shield epitopes and modulate immune recognition.", "mechanism": "Mediates viral entry via membrane fusion and receptor binding.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9557139" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect protein folding and virion assembly.", "mechanism": "Essential for viral assembly and morphogenesis.", "protein": "Membrane protein (M-protein)", "relationship_type": "causal", "source_pmcid": "PMC9557139" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may influence function, but not detailed in this article.", "mechanism": "Involved in virus assembly, budding, and pathogenesis.", "protein": "Envelope protein (E-protein)", "relationship_type": "causal", "source_pmcid": "PMC9557139" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Glycosylation status not detailed in this article.", "mechanism": "Packages viral RNA and regulates replication.", "protein": "Nucleocapsid protein (N-protein)", "relationship_type": "causal", "source_pmcid": "PMC9557139" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "Essential for viral polyprotein processing; inhibition blocks replication.", "protein": "3-chymotrypsin-like protease (3CLpro/Mpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9557139" }, { "confidence": "medium", "disease": "Feline infectious peritonitis", "glycan_involvement": "Glycosylation modulates host interaction.", "mechanism": "Mediates viral entry in feline coronavirus.", "protein": "Spike protein (S-protein)", "relationship_type": "causal", "source_pmcid": "PMC9557139" }, { "confidence": "high", "disease": "Feline infectious peritonitis", "glycan_involvement": "Not a glycoprotein; no glycan involvement.", "mechanism": "GC376 inhibits 3CLpro, blocking viral replication.", "protein": "3-chymotrypsin-like protease (3CLpro/Mpro)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9557139" }, { "confidence": "high", "disease": "Acquired von Willebrand Disease (aVWD)", "glycan_involvement": "vWF is a heavily glycosylated protein; glycosylation is essential for multimer formation and function.", "mechanism": "Loss of high molecular weight vWF multimers during ECMO/LVAD/ECLS leads to defective platelet adhesion and bleeding.", "protein": "von Willebrand Factor (vWF)", "relationship_type": "causal", "source_pmcid": "PMC9585390" }, { "confidence": "high", "disease": "Bleeding in ECMO/LVAD patients", "glycan_involvement": "Glycosylation stabilizes vWF multimers; loss affects function.", "mechanism": "Device-induced shear stress causes loss of vWF HMW multimers, resulting in bleeding tendency.", "protein": "von Willebrand Factor (vWF)", "relationship_type": "causal/biomarker", "source_pmcid": "PMC9585390" }, { "confidence": "medium", "disease": "Coagulopathy in liver failure", "glycan_involvement": "Glycosylation affects vWF clearance and activity.", "mechanism": "Altered vWF levels and function contribute to bleeding risk in liver failure.", "protein": "von Willebrand Factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC9585390" }, { "confidence": "high", "disease": "Disseminated intravascular coagulopathy (DIC)", "glycan_involvement": "Fibrinogen is N-glycosylated, which is important for secretion and function.", "mechanism": "Low fibrinogen levels are associated with bleeding in DIC; replacement therapy (Fibclot) used to restore hemostasis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9585390" }, { "confidence": "high", "disease": "Post-partum haemorrhage (PPH)", "glycan_involvement": "Glycosylation required for fibrinogen stability and clot formation.", "mechanism": "Fibrinogen concentrate used to correct hypofibrinogenemia and control bleeding.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585390" }, { "confidence": "medium", "disease": "Cardiac surgery-associated bleeding", "glycan_involvement": "FXIII is glycosylated; glycosylation affects secretion and activity.", "mechanism": "FXIII concentrate used to stabilize clots in uncontrolled bleeding after cardiac surgery.", "protein": "Coagulation Factor XIII", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585390" }, { "confidence": "medium", "disease": "Trauma-induced coagulopathy", "glycan_involvement": "FV is glycosylated; glycosylation affects stability and function.", "mechanism": "Low FV levels in trauma patients not corrected by standard therapy; FV replacement improves survival in models.", "protein": "Coagulation Factor V", "protein_enriched": { "function": "Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin", "gene_name": "F5", "glycan_count": 77, "glycosylation_sites_count": 27, "glytoucan_ids": [ "G00031MO", "G10225UW", "G29931IJ", "G57321FI", "G74722FL", "G39558MO", "G43417UB", "G81006GJ", "G22140GZ", "G50045TK", "G72291OX", "G53434XO", "G63628AV", "G29068FM", "G27391WQ", "G58001LT", "G23294PN", "G82463GQ", "G84452RH", "G49108TO", "G00912UN", "G22310AV", "G35029YA", "G56784JY", "G62765YT", "G70418MS", "G78790NZ", "G91473PK", "G48414YA", "G57888GL", "G62461SM", "G04854VP", "G05933EN", "G06356OH", "G49644CL", "G31433PN", "G39595FH", "G35305EF", "G37881RL", "G55383ZG", "G81263BG", "G99966GV", "G08606CV", "G15169WU", "G23453IV", "G31916IQ", "G57776ZU", "G00033MO", "G32550BI", "G03382KH", "G06110VR", "G10256JP", "G25451PN", "G25637MV", "G29880MM", "G34730YF", "G51895WL", "G55220VL", "G82119TF", "G84820NF", "G98205FV", "G99858XP", "G47748JZ", "G59626AS", "G05724UK", "G39188ZX", "G72735IY", "G80966KZ", "G27993JQ", "G33791AF", "G34617SM", "G41882MT", "G50757KG", "G66760KM", "G72667IM", "G93656SY", "G08918WF" ], "uniprot_id": "P12259" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585390" }, { "confidence": "low", "disease": "Thrombocytopenia", "glycan_involvement": "Extracellular histones may be post-translationally modified, but direct glycosylation role unclear.", "mechanism": "Extracellular histones (including H3) are elevated during ECMO and may contribute to prothrombotic tendency and thrombocytopenia.", "protein": "Histone H3", "relationship_type": "causal (potential)", "source_pmcid": "PMC9585390" }, { "confidence": "medium", "disease": "Cardiac surgery-associated bleeding", "glycan_involvement": "Glycosylation required for vWF function.", "mechanism": "Acquired vWD can develop post-surgery, contributing to bleeding.", "protein": "von Willebrand Factor (vWF)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9585390" }, { "confidence": "high", "disease": "Trauma-induced coagulopathy", "glycan_involvement": "N-glycosylation required for fibrinogen function.", "mechanism": "Fibrinogen depletion is a key driver of clot instability in trauma; replacement restores clot stability.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9585390" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "N-glycosylation of CD4 modulates HIV binding affinity.", "mechanism": "HIV binds to CD4 glycoprotein on T cells to initiate infection.", "protein": "CD4", "protein_enriched": { "function": "Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primari", "gene_name": "CD4", "glycan_count": 58, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G03860PZ", "G05950HG", "G06356OH", "G07995VK", "G17689DH", "G18188WJ", "G20779SK", "G20966IA", "G22310AV", "G23863VK", "G27561QX", "G30460NZ", "G35599NO", "G36191CD", "G37166HP", "G37738XF", "G38756OC", "G44276EF", "G45498YC", "G45560HM", "G48414YA", "G50045TK", "G52622SW", "G53450AF", "G53752TA", "G53962WT", "G57413FT", "G64132UH", "G65890UA", "G77252PU", "G78059CC", "G84452RH", "G87633UQ", "G89878AA", "G01650EU", "G10773YW", "G23294PN", "G31852PQ", "G34730YF", "G37399XV", "G45395BF", "G82463GQ", "G05724UK", "G06110VR", "G20425TQ", "G23453IV", "G29880MM", "G39188ZX", "G45864TJ", "G46687AB", "G47518TP", "G60145BJ", "G63923YN", "G64527OM", "G72797UR", "G81295CK", "G88433PA", "G94854LT" ], "uniprot_id": "P01730" }, "relationship_type": "causal", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Extensive N-glycosylation shields gp120 from immune recognition.", "mechanism": "gp120 mediates viral entry by binding CD4 and co-receptors.", "protein": "HIV-1 Envelope Glycoprotein gp120", "relationship_type": "causal", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "HIV/AIDS", "glycan_involvement": "Antibody glycosylation affects effector function and half-life.", "mechanism": "VH3810109 targets CD4-binding site on gp120, neutralizing HIV.", "protein": "VH3810109 (N6LS)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation modulates antigenicity and immune evasion.", "mechanism": "Spike protein is the main antigen for vaccine-induced immunity.", "protein": "SARS-CoV-2 Spike Glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "Hepatitis B", "glycan_involvement": "N-glycosylation affects secretion and immune recognition.", "mechanism": "HBsAg is used for diagnosis and monitoring of HBV infection.", "protein": "HBsAg (Hepatitis B surface antigen)", "protein_enriched": { "function": "Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in developme", "gene_name": "X", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P03165" }, "relationship_type": "biomarker", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "Hepatitis C", "glycan_involvement": "N-glycosylation shields E2 from neutralizing antibodies.", "mechanism": "E2 mediates viral entry and is a target for neutralizing antibodies.", "protein": "HCV Envelope Glycoprotein E2", "relationship_type": "causal", "source_pmcid": "PMC9585422" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may affect enzyme stability and drug binding.", "mechanism": "Integrase inhibitors block viral DNA integration.", "protein": "HIV-1 Integrase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585422" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation can modulate protease activity.", "mechanism": "Protease inhibitors block viral maturation.", "protein": "HIV-1 Protease", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585422" }, { "confidence": "medium", "disease": "HIV/AIDS", "glycan_involvement": "Glycosylation may affect enzyme function.", "mechanism": "RT inhibitors block viral replication.", "protein": "HIV-1 Reverse Transcriptase", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9585422" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "O-glycosylation modulates immune recognition.", "mechanism": "Nucleocapsid protein is used for serological diagnosis.", "protein": "SARS-CoV-2 Nucleocapsid Protein", "relationship_type": "biomarker", "source_pmcid": "PMC9585422" }, { "confidence": "high", "disease": "STEMI", "glycan_involvement": "Glycosylation is essential for proper folding and function of the IIb/IIIa complex.", "mechanism": "Glycoprotein IIb/IIIa mediates platelet aggregation; inhibitors reduce thrombus formation in STEMI.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9619531" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Altered glycosylation may affect receptor activation and thrombogenicity.", "mechanism": "COVID-19 increases thrombus burden, leading to greater use of glycoprotein IIb/IIIa inhibitors.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9619531" }, { "confidence": "medium", "disease": "Stent thrombosis", "glycan_involvement": "Glycosylation modulates ligand binding and inhibitor efficacy.", "mechanism": "Inhibition of glycoprotein IIb/IIIa reduces risk of stent thrombosis in high-thrombus settings.", "protein": "Glycoprotein IIb/IIIa", "protein_enriched": { "function": "Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognize", "gene_name": "ITGA2B", "glycan_count": 4, "glycosylation_sites_count": 7, "glytoucan_ids": [ "G53434XO", "G58001LT", "G29068FM", "G43417UB" ], "uniprot_id": "P08514" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9619531" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "GPNMB is a glycoprotein; glycosylation may affect its stability and detection as a biomarker.", "mechanism": "Elevated plasma GPNMB is associated with cardiac damage post-chemotherapy.", "protein": "Glycoprotein nonmetastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation may modulate GPNMB's secretion and function.", "mechanism": "Elevated GPNMB correlates with ischemic heart disease after cHL treatment.", "protein": "Glycoprotein nonmetastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "ALCAM is heavily N-glycosylated, which influences its cell adhesion properties and plasma levels.", "mechanism": "Increased ALCAM levels are associated with cardiac damage post-treatment.", "protein": "Activated leukocyte cell adhesion molecule (ALCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "N-glycosylation affects ALCAM's stability and biomarker potential.", "mechanism": "ALCAM elevation is linked to ischemic heart disease in cHL survivors.", "protein": "Activated leukocyte cell adhesion molecule (ALCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Heart failure", "glycan_involvement": "CYR61 is a secreted glycoprotein; glycosylation may regulate its extracellular matrix interactions.", "mechanism": "CYR61 is upregulated in plasma after cardiac injury from chemotherapy.", "protein": "Cysteine rich protein 61 (CYR61)", "protein_enriched": { "function": "Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in ", "gene_name": "CCN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00622" }, "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Ischemic heart disease", "glycan_involvement": "Glycosylation may influence CYR61's role in tissue remodeling.", "mechanism": "CYR61 levels are associated with ischemic heart disease post-cHL treatment.", "protein": "Cysteine rich protein 61 (CYR61)", "protein_enriched": { "function": "Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in ", "gene_name": "CCN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00622" }, "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Cardiotoxicity in Hodgkin lymphoma patients", "glycan_involvement": "Glycosylation impacts GPNMB's plasma half-life and detection.", "mechanism": "GPNMB is a candidate biomarker for detecting cardiotoxicity after chemotherapy.", "protein": "Glycoprotein nonmetastatic melanoma protein B (GPNMB)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Cardiotoxicity in Hodgkin lymphoma patients", "glycan_involvement": "N-glycosylation modulates ALCAM's function and biomarker utility.", "mechanism": "ALCAM is associated with emerging cardiac toxicity in cHL survivors.", "protein": "Activated leukocyte cell adhesion molecule (ALCAM)", "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "medium", "disease": "Cardiotoxicity in Hodgkin lymphoma patients", "glycan_involvement": "Glycosylation may affect CYR61's secretion and activity.", "mechanism": "CYR61 is linked to cardiac toxicity following cHL therapy.", "protein": "Cysteine rich protein 61 (CYR61)", "protein_enriched": { "function": "Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in ", "gene_name": "CCN1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "O00622" }, "relationship_type": "biomarker", "source_pmcid": "PMC9621517" }, { "confidence": "high", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Direct accumulation of glycogen (a glucose polymer) in liver cells", "mechanism": "Excessive accumulation of glycogen in hepatocytes due to hyperglycemia and hyperinsulinemia", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC9624548" }, { "confidence": "high", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Insulin signaling increases glycogen (glycan) synthesis", "mechanism": "High insulin doses promote glycogen synthesis and suppress glycogenolysis in hepatocytes", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC9624548" }, { "confidence": "medium", "disease": "Glycogenic Hepatopathy", "glycan_involvement": "Glucagon normally promotes glycogen breakdown; dysfunction leads to excess glycogen", "mechanism": "Abnormal glucagon activity may impair glycogenolysis, contributing to glycogen accumulation", "protein": "Glucagon", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "Gcg", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55095" }, "relationship_type": "causal (suspected)", "source_pmcid": "PMC9624548" }, { "confidence": "high", "disease": "Congenital Glycogen Storage Disorders", "glycan_involvement": "Defective breakdown of glycogen (glycan)", "mechanism": "Enzyme deficiencies in glycogenolysis pathway cause glycogen accumulation", "protein": "Glycogen", "relationship_type": "causal", "source_pmcid": "PMC9624548" }, { "confidence": "medium", "disease": "Nonalcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Presence of excess glycogen (glycan) in GH, not NAFLD", "mechanism": "Glycogen accumulation distinguishes GH from NAFLD on biopsy", "protein": "Glycogen", "relationship_type": "differential biomarker", "source_pmcid": "PMC9624548" }, { "confidence": "medium", "disease": "Hypertension in Type 2 Diabetes", "glycan_involvement": "MR is a glycoprotein; glycosylation may affect receptor function and ligand binding.", "mechanism": "Abnormal activation of MR leads to MR-related hypertension in T2D patients.", "protein": "Mineralocorticoid Receptor (MR)", "relationship_type": "causal", "source_pmcid": "PMC9624635" }, { "confidence": "low", "disease": "Impaired Glucose Tolerance", "glycan_involvement": "Glycosylation may modulate MR cell surface expression and signaling.", "mechanism": "MR activation contributes to hypertension in IGT, possibly via metabolic and vascular effects.", "protein": "Mineralocorticoid Receptor (MR)", "relationship_type": "causal", "source_pmcid": "PMC9624635" }, { "confidence": "high", "disease": "Antiphospholipid syndrome (APS)", "glycan_involvement": "Beta-2 glycoprotein I is a glycoprotein; its glycosylation is essential for antigenicity and antibody recognition.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are diagnostic markers for APS; their presence is associated with hypercoagulability.", "protein": "Beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC9624651" }, { "confidence": "medium", "disease": "Adrenal hemorrhage", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I may influence antibody binding and pathogenicity.", "mechanism": "Antibodies against beta-2 glycoprotein I promote thrombosis, which can lead to adrenal vein thrombosis and subsequent hemorrhage.", "protein": "Beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC9624651" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "Transferrin is a glycoprotein; glycosylation affects its serum half-life and function.", "mechanism": "Elevated transferrin levels used as exclusion criterion for NASH diagnosis, indicating altered iron metabolism in liver disease.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9624696" }, { "confidence": "medium", "disease": "Nonalcoholic Steatohepatitis (NASH)", "glycan_involvement": "CRP is a glycoprotein; glycosylation modulates its stability and immune function.", "mechanism": "High-sensitivity CRP (hsCRP) measured as an inflammatory marker associated with NASH.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9624696" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation stabilizes lipase secretion and activity.", "mechanism": "Release of pancreatic lipase during pancreatitis leads to breakdown of triglycerides, generating free fatty acids.", "protein": "Pancreatic lipase", "protein_enriched": { "function": "Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows consi", "gene_name": "PNLIP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16233" }, "relationship_type": "causal", "source_pmcid": "PMC9624780" }, { "confidence": "medium", "disease": "Hypocalcemia", "glycan_involvement": "Glycosylation affects enzyme stability and secretion.", "mechanism": "Lipase-mediated free fatty acids bind calcium, forming insoluble salts and reducing serum calcium.", "protein": "Pancreatic lipase", "protein_enriched": { "function": "Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows consi", "gene_name": "PNLIP", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16233" }, "relationship_type": "causal", "source_pmcid": "PMC9624780" }, { "confidence": "high", "disease": "Acute pancreatitis", "glycan_involvement": "Glycosylation influences serum half-life and detection.", "mechanism": "Elevated serum amylase is a diagnostic marker for pancreatitis.", "protein": "Amylase", "relationship_type": "biomarker", "source_pmcid": "PMC9624780" }, { "confidence": "medium", "disease": "Hypocalcemia", "glycan_involvement": "Minor glycosylation, but not central to function in this context.", "mechanism": "Low albumin reduces total serum calcium; albumin binds calcium in blood.", "protein": "Albumin", "protein_enriched": { "function": "Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transport", "gene_name": "ALB", "glycan_count": 8, "glycosylation_sites_count": 24, "glytoucan_ids": [ "G43417UB", "G48414YA", "G53276NK", "G57321FI", "G29068FM", "G49108TO", "G73319KU", "G74722FL" ], "uniprot_id": "P02768" }, "relationship_type": "biomarker", "source_pmcid": "PMC9624780" }, { "confidence": "high", "disease": "Statin-associated necrotizing autoimmune myopathy", "glycan_involvement": "Potential involvement as HMGCR is a glycoprotein; glycosylation may affect antigenicity.", "mechanism": "Autoantibodies against HMGCR trigger immune-mediated muscle necrosis after statin exposure.", "protein": "HMGCR", "relationship_type": "causal", "source_pmcid": "PMC9625074" }, { "confidence": "medium", "disease": "Statin-associated necrotizing autoimmune myopathy", "glycan_involvement": "SRP antigen is a glycoprotein; glycosylation may modulate immune recognition.", "mechanism": "Autoantibodies against SRP antigen are associated with some cases of necrotizing myopathy.", "protein": "SRP antigen", "relationship_type": "biomarker", "source_pmcid": "PMC9625074" }, { "confidence": "high", "disease": "Graves\u2019 disease", "glycan_involvement": "TSI is an immunoglobulin with N-glycosylation affecting stability and receptor binding", "mechanism": "TSI binds to TSH receptor, stimulating thyroid hormone production", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC9625207" }, { "confidence": "high", "disease": "Graves\u2019 disease", "glycan_involvement": "TRAb glycosylation modulates antibody function and immune recognition", "mechanism": "TRAb activates TSH receptor, leading to hyperthyroidism", "protein": "Thyrotropin Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC9625207" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation influences TSI half-life and activity", "mechanism": "TSI overstimulates thyroid hormone synthesis causing thyrotoxicosis", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "causal", "source_pmcid": "PMC9625207" }, { "confidence": "medium", "disease": "Thyrotoxicosis", "glycan_involvement": "Glycosylation affects antibody-receptor interaction", "mechanism": "TRAb mimics TSH, driving excess thyroid hormone production", "protein": "Thyrotropin Receptor Antibody (TRAb)", "relationship_type": "causal", "source_pmcid": "PMC9625207" }, { "confidence": "low", "disease": "Covid-19 infection", "glycan_involvement": "Altered glycosylation in infection may enhance autoantibody generation", "mechanism": "Covid-19 may trigger autoantibody production including TSI", "protein": "Thyroid Stimulating Immunoglobulin (TSI)", "relationship_type": "biomarker", "source_pmcid": "PMC9625207" }, { "confidence": "low", "disease": "Covid-19 infection", "glycan_involvement": "Immune dysregulation and glycosylation changes may promote autoimmunity", "mechanism": "Covid-19 may induce TRAb production, precipitating Graves\u2019 disease", "protein": "Thyrotropin Receptor Antibody (TRAb)", "relationship_type": "biomarker", "source_pmcid": "PMC9625207" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "CRP is a glycoprotein; glycosylation affects its stability and function.", "mechanism": "CRP is an inflammatory marker elevated in hepatic fibrosis.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9627020" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "Non-enzymatic glycation of hemoglobin.", "mechanism": "HbA1c reflects chronic hyperglycemia and is associated with diabetes.", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC9627020" }, { "confidence": "medium", "disease": "Hepatic fibrosis", "glycan_involvement": "Reflects increased glycation due to hyperglycemia.", "mechanism": "Elevated HbA1c (\u22656.5%) is associated with higher odds of advanced hepatic fibrosis (F4).", "protein": "Hemoglobin A1c", "relationship_type": "biomarker", "source_pmcid": "PMC9627020" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Glycosylation modulates CRP's inflammatory activity.", "mechanism": "CRP is elevated in NASH due to systemic inflammation.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9627020" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease (NAFLD)", "glycan_involvement": "Adiponectin is a glycoprotein; glycosylation is essential for its secretion and function.", "mechanism": "Increased plasma adiponectin is associated with reduced liver injury and improved insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC9627139" }, { "confidence": "medium", "disease": "Insulin resistance", "glycan_involvement": "Glycosylation modulates adiponectin multimerization and activity.", "mechanism": "Higher adiponectin levels improve insulin sensitivity.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC9627139" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "ALT is glycosylated, which may affect its stability and secretion.", "mechanism": "ALT levels correlate with liver steatosis and liver injury.", "protein": "ALT (Alanine aminotransferase)", "protein_enriched": { "function": "Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also fu", "gene_name": "Aldoa", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P05064" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627139" }, { "confidence": "high", "disease": "Liver steatosis", "glycan_involvement": "AST glycosylation may influence its serum levels.", "mechanism": "AST levels correlate with liver steatosis and liver injury.", "protein": "AST (Aspartate aminotransferase)", "relationship_type": "biomarker", "source_pmcid": "PMC9627139" }, { "confidence": "medium", "disease": "Type 2 diabetes mellitus", "glycan_involvement": "Glycosylation is required for adiponectin's insulin-sensitizing effects.", "mechanism": "Increased adiponectin improves glycemic control.", "protein": "Adiponectin", "protein_enriched": { "function": "Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and", "gene_name": "ADIPOQ", "glycan_count": 2, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G53434XO", "G43417UB" ], "uniprot_id": "Q15848" }, "relationship_type": "protective", "source_pmcid": "PMC9627139" }, { "confidence": "high", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "IL-7 is a glycoprotein; glycosylation is required for secretion and stability.", "mechanism": "IL-7 levels correlate with inflammation and metabolic dysfunction in obese African Americans with T2D.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9627267" }, { "confidence": "high", "disease": "Obesity-associated inflammation", "glycan_involvement": "Glycosylation modulates IL-7 bioactivity and receptor interaction.", "mechanism": "Elevated IL-7 is associated with increased inflammatory markers in obese individuals.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "Glycosylation affects IL-7 stability in circulation.", "mechanism": "IL-7 levels correlate with liver damage markers (AST, ALT), especially in women.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "high", "disease": "Dyslipidemia (high LDL)", "glycan_involvement": "PCSK9 glycosylation is essential for secretion and LDL receptor interaction.", "mechanism": "Active PCSK9 correlates with high LDL and is linked to inflammation.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation modulates PCSK9 function.", "mechanism": "PCSK9 activity is increased in women with high IL-7 and T2D, linking lipid metabolism and inflammation.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "AST is glycosylated, affecting serum stability.", "mechanism": "AST is a standard marker for liver injury; correlates with IL-7 in women.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Liver damage", "glycan_involvement": "ALT is glycosylated, affecting serum stability.", "mechanism": "ALT is a standard marker for liver injury; correlates with IL-7 in women.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Dyslipidemia (high LDL)", "glycan_involvement": "Glycosylation required for IL-7 secretion.", "mechanism": "IL-7 levels correlate with active PCSK9 and high LDL in women.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Obesity-associated inflammation", "glycan_involvement": "Glycosylation required for PCSK9 secretion.", "mechanism": "Active PCSK9 is linked to inflammation in obese individuals.", "protein": "PCSK9", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "medium", "disease": "Sex-specific immune response in T2D", "glycan_involvement": "Glycosylation affects IL-7 function.", "mechanism": "IL-7 shows sex-specific correlations with metabolic and liver markers, indicating sex as a variable in immune response.", "protein": "Interleukin-7 (IL-7)", "relationship_type": "biomarker", "source_pmcid": "PMC9627267" }, { "confidence": "high", "disease": "Cushing syndrome (CS)", "glycan_involvement": "GlycA measures N-acetyl methyl groups from glycan chains on acute-phase glycoproteins.", "mechanism": "Elevated GlycA reflects increased chronic inflammation in CS, correlating with higher cardiometabolic risk.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "high", "disease": "Pheochromocytoma/paraganglioma (PPGL)", "glycan_involvement": "GlycA quantifies glycosylation on acute-phase proteins.", "mechanism": "Increased GlycA indicates chronic inflammation and elevated cardiometabolic risk in PPGL.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "high", "disease": "Mild autonomous cortisol secretion (MACS)", "glycan_involvement": "GlycA is derived from glycan modifications on circulating glycoproteins.", "mechanism": "Higher GlycA levels signal inflammation and increased cardiometabolic risk in MACS.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "high", "disease": "Nonfunctioning adrenal adenoma (NFA)", "glycan_involvement": "Reflects glycosylation status of acute-phase glycoproteins.", "mechanism": "Elevated GlycA in NFA patients is associated with adverse metabolic profile and inflammation.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "medium", "disease": "Primary aldosteronism (PA)", "glycan_involvement": "GlycA is a readout of glycan modifications on plasma glycoproteins.", "mechanism": "Moderately increased GlycA in PA indicates inflammation and cardiometabolic risk.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "high", "disease": "Cardiometabolic disorders", "glycan_involvement": "GlycA quantifies glycosylation on multiple acute-phase glycoproteins.", "mechanism": "GlycA is a validated marker of systemic inflammation and predicts adverse cardiometabolic outcomes.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "high", "disease": "Diabetes mellitus", "glycan_involvement": "GlycA reflects glycan modifications on glycoproteins linked to insulin resistance.", "mechanism": "Higher GlycA correlates with increased LP-IR index, predicting incident diabetes.", "protein": "GlycA", "relationship_type": "biomarker", "source_pmcid": "PMC9627405" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "IL-3 is a glycoprotein; glycosylation may affect its stability and function.", "mechanism": "Serum IL-3 levels are altered in response to high glucose; upregulated in women, downregulated in men with high HbA1c.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Glycosylation may modulate IL-3's anti-inflammatory activity.", "mechanism": "IL-3 levels decrease as BMI increases, suggesting loss of anti-inflammatory/protective role with obesity.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may influence IL-3's interaction with lipid metabolism pathways.", "mechanism": "IL-3 correlates with serum lipids (HDL, triglycerides) implicated in CVD risk.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Atherosclerosis", "glycan_involvement": "Glycosylation may affect IL-3's stability and receptor binding.", "mechanism": "IL-3 is correlated with cholesterol and lipids known to cause atherosclerosis.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Metabolic Syndrome", "glycan_involvement": "Glycosylation may regulate IL-3's inflammatory signaling.", "mechanism": "IL-3 is involved in the inflammatory response associated with metabolic syndrome.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Non-Alcoholic Fatty Liver Disease (NAFLD)", "glycan_involvement": "Glycosylation may modulate IL-3's function in hepatic inflammation.", "mechanism": "IL-3 is implicated in the inflammatory cascade preceding NAFLD.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation may be required for IL-3's anti-inflammatory activity.", "mechanism": "IL-3 may be anti-inflammatory and lose its protective role as blood sugar remains elevated.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "protective", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Obesity", "glycan_involvement": "Glycosylation may affect IL-3's regulatory capacity.", "mechanism": "High BMI may trigger pro-inflammatory cytokines that IL-3 cannot suppress.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "causal", "source_pmcid": "PMC9627515" }, { "confidence": "low", "disease": "Cardiovascular Disease (CVD)", "glycan_involvement": "Glycosylation may influence IL-3's lipid regulatory functions.", "mechanism": "IL-3 may regulate cholesterol and lipid management, impacting CVD risk.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "regulatory", "source_pmcid": "PMC9627515" }, { "confidence": "medium", "disease": "Type 2 Diabetes (T2D)", "glycan_involvement": "Glycosylation may contribute to sex-specific effects.", "mechanism": "Sex-specific differences: IL-3 upregulated in women, downregulated in men with high glucose.", "protein": "IL-3", "protein_enriched": { "function": "Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-", "gene_name": "IL3", "glycan_count": 0, "glycosylation_sites_count": 2, "glytoucan_ids": [], "uniprot_id": "P08700" }, "relationship_type": "biomarker", "source_pmcid": "PMC9627515" }, { "confidence": "high", "disease": "Acute Kidney Injury (AKI)", "glycan_involvement": "Fetuin-A is a glycoprotein; glycosylation may affect exosomal sorting and stability.", "mechanism": "Increased in urinary exosomes/sEVs after cisplatin-induced AKI, possibly secreted from damaged proximal tubule cells.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "IgA Nephropathy (IgAN)", "glycan_involvement": "Glycosylation modulates anti-protease activity and exosomal trafficking.", "mechanism": "Elevated in urinary exosomes/sEVs in IgAN, may induce fibrinolysis in response to hematuria.", "protein": "Alpha-1-antitrypsin", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "IgA Nephropathy (IgAN)", "glycan_involvement": "Glycosylation affects stability and immune recognition.", "mechanism": "Increased in urinary exosomes/sEVs, indicating mesangial inflammation.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "Thin Basement Membrane Nephropathy (TBMN)", "glycan_involvement": "N-glycosylation required for enzymatic activity and exosomal localization.", "mechanism": "Higher in TBMN urinary exosomes/sEVs; modulates MAPK pathways and immune regulation.", "protein": "Aminopeptidase N", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "medium", "disease": "Thin Basement Membrane Nephropathy (TBMN)", "glycan_involvement": "Glycosylation may regulate function and exosomal sorting.", "mechanism": "Elevated in TBMN urinary exosomes/sEVs; associated with vessel repair.", "protein": "Vasorin precursor", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Glycosylation may affect stability and exosomal release.", "mechanism": "Decreased in urinary exosomes/sEVs from DN patients; regulates calcium transport and cell signaling.", "protein": "Regucalcin", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "Diabetic Nephropathy (DN)", "glycan_involvement": "Heavy glycosylation modulates inhibitory function and exosomal targeting.", "mechanism": "Increased in DN urinary exosomes/sEVs; serine protease inhibitor activity.", "protein": "Alpha-microglobulin/bikunin precursor (AMBP)", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "medium", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "Glycosylation critical for cell adhesion and exosomal incorporation.", "mechanism": "Enriched in peritoneal dialysis effluent EVs from patients with stable peritoneal membrane function.", "protein": "Thy-1 membrane glycoprotein (CD90)", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "medium", "disease": "End-Stage Renal Disease (ESRD)", "glycan_involvement": "Proteoglycan with glycosaminoglycan chains; glycosylation affects ECM interactions.", "mechanism": "Enriched in peritoneal dialysis effluent EVs; associated with ultrafiltration capacity.", "protein": "Biglycan", "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "Vancomycin-induced AKI", "glycan_involvement": "Glycosylation modulates complement activation and exosomal sorting.", "mechanism": "Significantly increased in urinary exosomes/sEVs; indicates complement activation and inflammation.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC9635898" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "CRP is a glycoprotein; glycosylation is required for its stability and function.", "mechanism": "CRP is elevated due to cytokine storm and inflammation; correlates with disease severity.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "medium", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation affects CRP's serum half-life and immune recognition.", "mechanism": "Higher CRP levels are associated with increased risk of mortality, though less predictive than LDH/ferritin.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "high", "disease": "Severe COVID-19", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect secretion and immune modulation.", "mechanism": "Ferritin is elevated in severe cases due to inflammation and immune activation.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "high", "disease": "COVID-19 mortality", "glycan_involvement": "Glycosylation may influence ferritin's clearance and inflammatory signaling.", "mechanism": "High ferritin levels independently predict mortality in severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "medium", "disease": "COVID-19 associated renal failure", "glycan_involvement": "Glycosylation may affect ferritin's interaction with immune cells.", "mechanism": "Ferritin correlates with markers of kidney damage (urea, creatinine) in severe COVID-19.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "medium", "disease": "COVID-19 associated respiratory failure", "glycan_involvement": "Glycosylation is essential for CRP's function in inflammation.", "mechanism": "CRP correlates with reduced oxygen saturation and respiratory performance.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "medium", "disease": "COVID-19 associated respiratory failure", "glycan_involvement": "Glycosylation may modulate ferritin's inflammatory role.", "mechanism": "Ferritin levels negatively correlate with oxygen saturation (SpO2).", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for CRP's stability and immune function.", "mechanism": "CRP is an early marker of infection and inflammation in COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects ferritin's serum levels and immune interactions.", "mechanism": "Ferritin is elevated in COVID-19 due to acute phase response.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "medium", "disease": "COVID-19 associated renal failure", "glycan_involvement": "Glycosylation may influence CRP's clearance and immune effects.", "mechanism": "CRP correlates with markers of kidney damage in severe COVID-19.", "protein": "C-reactive protein", "relationship_type": "biomarker", "source_pmcid": "PMC9638333" }, { "confidence": "high", "disease": "Herpes simplex virus infection (HSV-1, HSV-2)", "glycan_involvement": "Herpesvirus envelope glycoproteins are heavily glycosylated, facilitating host entry and immune evasion.", "mechanism": "Viral CDK homologs and their interaction with host CDK2 are essential for viral replication and latency.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9651104" }, { "confidence": "high", "disease": "Epstein-Barr virus-associated lymphoproliferative diseases", "glycan_involvement": "Glycosylation of viral envelope proteins is critical for infectivity and immune modulation.", "mechanism": "Viral kinases and glycoproteins modulate host cell cycle and immune signaling, contributing to lymphomagenesis.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9651104" }, { "confidence": "high", "disease": "Kaposi's sarcoma", "glycan_involvement": "Glycosylation of viral glycoproteins aids in immune evasion and tumorigenesis.", "mechanism": "Viral kinases and glycoproteins drive oncogenic transformation in immunocompromised hosts.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9651104" }, { "confidence": "medium", "disease": "Burkitt's lymphoma", "glycan_involvement": "Glycosylation modulates viral-host interactions and immune escape.", "mechanism": "Viral proteins, including glycoproteins, alter host cell signaling and proliferation.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9651104" }, { "confidence": "medium", "disease": "Nasopharyngeal carcinoma", "glycan_involvement": "Glycosylation of viral proteins enhances cell tropism and immune evasion.", "mechanism": "Viral kinases and glycoproteins contribute to oncogenesis in epithelial cells.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9651104" }, { "confidence": "medium", "disease": "B-cell lymphoproliferative syndromes", "glycan_involvement": "Glycosylation is essential for viral infectivity and immune modulation.", "mechanism": "Viral proteins, including glycoproteins, disrupt normal B-cell regulation.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9651104" }, { "confidence": "high", "disease": "Herpes simplex virus infection (HSV-1, HSV-2)", "glycan_involvement": "Targeting glycoprotein-protein interactions may disrupt viral entry and replication.", "mechanism": "Phytochemicals (epicatechin, rac 8-prenylnaringenin, apigenin, D-(+)-catechin) inhibit viral CDK complex, blocking replication.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9651104" }, { "confidence": "high", "disease": "Herpes simplex virus infection (HSV-1, HSV-2)", "glycan_involvement": "Glycosylation of viral proteins may contribute to drug resistance and immune evasion.", "mechanism": "Current drugs (aciclovir, famciclovir, penciclovir, valaciclovir) target viral DNA replication but are less effective against latent virus.", "protein": "Herpesvirus cyclin-dependent kinase complex (CDK2)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9651104" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I modulates antigenicity and autoantibody binding.", "mechanism": "Autoantibodies against beta-2 glycoprotein I promote thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9665187" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Glycosylation of beta-2 glycoprotein I influences antibody recognition.", "mechanism": "Anti-cardiolipin antibodies (often targeting beta-2 glycoprotein I complexes) are diagnostic and pathogenic in APS.", "protein": "cardiolipin-binding antibodies (anti-cardiolipin)", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9665187" }, { "confidence": "high", "disease": "antiphospholipid syndrome", "glycan_involvement": "Targets glycoprotein-phospholipid complexes; glycosylation may affect epitope exposure.", "mechanism": "Lupus anticoagulant (autoantibodies) interferes with phospholipid-dependent coagulation, increasing thrombosis risk.", "protein": "lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9665187" }, { "confidence": "medium", "disease": "vaccine-induced thrombotic thrombocytopenia", "glycan_involvement": "PF4 is a glycoprotein; glycosylation may influence immunogenicity.", "mechanism": "Anti-platelet factor 4 antibodies trigger platelet activation and thrombosis post-vaccination.", "protein": "platelet factor 4", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9665187" }, { "confidence": "high", "disease": "thrombosis", "glycan_involvement": "Glycosylation state affects immune recognition and function.", "mechanism": "Autoantibodies to beta-2 glycoprotein I promote hypercoagulability and thrombosis.", "protein": "beta-2 glycoprotein I", "relationship_type": "causal", "source_pmcid": "PMC9665187" }, { "confidence": "high", "disease": "thrombosis", "glycan_involvement": "Targets glycoprotein-phospholipid complexes.", "mechanism": "Presence of lupus anticoagulant is associated with increased risk of thrombosis.", "protein": "lupus anticoagulant", "relationship_type": "biomarker/causal", "source_pmcid": "PMC9665187" }, { "confidence": "medium", "disease": "systemic lupus erythematosus", "glycan_involvement": "Glycosylation modulates antigenicity.", "mechanism": "Anti-beta-2 glycoprotein I antibodies are found in SLE patients with antiphospholipid syndrome.", "protein": "beta-2 glycoprotein I", "relationship_type": "biomarker", "source_pmcid": "PMC9665187" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycoprotein VI is a glycosylated receptor essential for platelet-collagen interaction.", "mechanism": "Altered Glycoprotein VI signaling via SYK pathway contributes to platelet hyperreactivity and prothrombotic state in severe COVID-19.", "protein": "Glycoprotein VI", "relationship_type": "causal", "source_pmcid": "PMC9665211" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "P-Selectin is a heavily glycosylated adhesion molecule mediating platelet-leukocyte interactions.", "mechanism": "P-Selectin expression on platelets is used as a marker of platelet activation and is variable in severe COVID-19.", "protein": "P-Selectin", "relationship_type": "biomarker", "source_pmcid": "PMC9665211" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Fibrinogen is a glycoprotein; glycosylation affects its function in coagulation.", "mechanism": "Fibrinogen binding to platelets is used to assess platelet activation and sensitivity in COVID-19 patients.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9665211" }, { "confidence": "medium", "disease": "Thrombosis", "glycan_involvement": "Glycosylation is required for Glycoprotein VI function and surface expression.", "mechanism": "Glycoprotein VI-mediated platelet activation promotes thrombosis, especially in the context of COVID-19.", "protein": "Glycoprotein VI", "relationship_type": "causal", "source_pmcid": "PMC9665211" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc receptor \u03b3-chain is glycosylated, which may affect receptor assembly and signaling.", "mechanism": "Fc receptor \u03b3-chain associates with Glycoprotein VI, mediating antibody-induced platelet activation in COVID-19.", "protein": "Fc receptor \u03b3-chain", "relationship_type": "causal", "source_pmcid": "PMC9665211" }, { "confidence": "medium", "disease": "Immune Thrombocytopenia (ITP)", "glycan_involvement": "Glycosylation is essential for Glycoprotein VI function.", "mechanism": "SYK inhibition (e.g., fostamatinib) targeting Glycoprotein VI pathway is approved for ITP and may be beneficial in COVID-19-associated thrombosis.", "protein": "Glycoprotein VI", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9665211" }, { "confidence": "high", "disease": "MODY type 5 (Maturity Onset Diabetes of the Young type 5)", "glycan_involvement": "HNF1B regulates expression of glycoproteins involved in organ development; glycosylation status may affect protein stability and function.", "mechanism": "Mutations in HNF1B cause MODY type 5 by disrupting transcriptional regulation of genes involved in pancreatic, renal, and hepatic development.", "protein": "Hepatocyte Nuclear Factor 1B (HNF1B)", "relationship_type": "causal", "source_pmcid": "PMC9707326" }, { "confidence": "medium", "disease": "Cystic kidney disease", "glycan_involvement": "HNF1B regulates glycoproteins in renal tubules; altered glycosylation may contribute to cystogenesis.", "mechanism": "HNF1B mutations impair renal tubular development, leading to cyst formation.", "protein": "Hepatocyte Nuclear Factor 1B (HNF1B)", "relationship_type": "causal", "source_pmcid": "PMC9707326" }, { "confidence": "medium", "disease": "Diabetic hepatosclerosis", "glycan_involvement": "HNF1B regulates hepatic glycoproteins; glycosylation changes may affect liver matrix and function.", "mechanism": "HNF1B mutations can impair hepatic function and structure, predisposing to hepatosclerosis in diabetes.", "protein": "Hepatocyte Nuclear Factor 1B (HNF1B)", "relationship_type": "causal", "source_pmcid": "PMC9707326" }, { "confidence": "medium", "disease": "Gitelman syndrome-like tubulopathy", "glycan_involvement": "HNF1B-regulated glycoproteins in tubules may require proper glycosylation for transporter function.", "mechanism": "HNF1B mutations disrupt electrolyte transporters in renal tubules, mimicking Gitelman syndrome.", "protein": "Hepatocyte Nuclear Factor 1B (HNF1B)", "relationship_type": "causal", "source_pmcid": "PMC9707326" }, { "confidence": "high", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "vWF is a heavily glycosylated plasma glycoprotein; glycosylation affects its multimerization and function in coagulation.", "mechanism": "Increased expression in left atrium of cats with HCM, indicating endothelial activation and prothrombotic state.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Aortic thromboembolism (ATE)", "glycan_involvement": "Glycosylation modulates vWF's interaction with platelets and endothelium.", "mechanism": "Elevated vWF expression in HCM is associated with increased risk of thrombus formation.", "protein": "von Willebrand factor", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "E-selectin is a glycoprotein; its glycosylation is essential for ligand binding and leukocyte recruitment.", "mechanism": "Upregulated gene expression in HCM hearts, reflecting endothelial activation and inflammation.", "protein": "E-selectin", "protein_enriched": { "function": "Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in cap", "gene_name": "SELE", "glycan_count": 0, "glycosylation_sites_count": 11, "glytoucan_ids": [], "uniprot_id": "P16581" }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation required for proper trafficking and function.", "mechanism": "Increased expression in HCM, contributing to platelet-endothelial interactions and thrombosis.", "protein": "P-selectin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "N-glycosylation modulates ICAM-1's adhesive properties.", "mechanism": "Upregulated in HCM, mediating leukocyte adhesion and inflammation.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "Glycosylation affects ligand binding and cell adhesion.", "mechanism": "Increased expression in HCM, promoting leukocyte recruitment.", "protein": "VCAM-1", "protein_enriched": { "function": "Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation (PubMed:31310649). Acts as a major regulator", "gene_name": "VCAM1", "glycan_count": 56, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G06356OH", "G37881RL", "G48414YA", "G52527GH", "G56784JY", "G72747WU", "G77669RF", "G00912UN", "G08918WF", "G20706XG", "G27058EU", "G45395BF", "G80075MS", "G43417UB", "G82830MN", "G00273SJ", "G01160VV", "G02815KT", "G05962QB", "G07246CJ", "G09831WQ", "G14972EH", "G28622IK", "G30221QT", "G31852PQ", "G35541EV", "G39471UU", "G40834TG", "G41071NU", "G41247ZX", "G42124LM", "G43223CG", "G50856PC", "G55132BD", "G57776ZS", "G59324HL", "G62765YT", "G65414LI", "G69521XL", "G70232NH", "G70441OD", "G75568BH", "G79666IR", "G80479JV", "G80920RR", "G81637OR", "G83460ZZ", "G83646BJ", "G86880BF", "G87123QX", "G87661QW", "G90382BL", "G92135MA", "G93718GY", "G94665LC", "G98611JV" ], "uniprot_id": "P19320" }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "N-glycosylation regulates integrin activation and cell-cell interactions.", "mechanism": "Upregulated in HCM, involved in leukocyte adhesion and transmigration.", "protein": "\u03b22-integrin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Cardiogenic pleural effusion", "glycan_involvement": "SAA is glycosylated; glycosylation may affect its solubility and clearance.", "mechanism": "SAA is increased in cats with cardiogenic pleural effusion, indicating systemic inflammation.", "protein": "Serum amyloid A", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Aortic thromboembolism (ATE)", "glycan_involvement": "Fibrinogen is N-glycosylated; glycosylation affects clot formation and stability.", "mechanism": "Lower fibrinogen:SAA ratio in cats with pleural effusion is associated with lower ATE risk, suggesting enhanced fibrinolysis.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker/protective", "source_pmcid": "PMC9708443" }, { "confidence": "medium", "disease": "Hypertrophic cardiomyopathy (HCM)", "glycan_involvement": "VEGF glycosylation modulates receptor binding and bioactivity.", "mechanism": "Lower VEGF expression in HCM may reflect impaired angiogenesis or endothelial dysfunction.", "protein": "Vascular endothelial growth factor (VEGF)", "protein_enriched": { "function": "Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of bl", "gene_name": "Vegfa", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P16612" }, "relationship_type": "biomarker", "source_pmcid": "PMC9708443" }, { "confidence": "high", "disease": "Inflammation", "glycan_involvement": "Altered glycosylation increases pro-inflammatory activity.", "mechanism": "Elevated levels indicate acute and chronic inflammation in elderly.", "protein": "Alpha-1-acid glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "high", "disease": "Immunosenescence", "glycan_involvement": "Reduced galactosylation and sialylation promote inflammation.", "mechanism": "Age-related changes in IgG glycosylation reflect immune system aging.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "medium", "disease": "Iron deficiency", "glycan_involvement": "Changes in N-glycosylation affect iron binding.", "mechanism": "Altered glycoforms signal iron metabolism disturbances in elderly.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "medium", "disease": "Anemia", "glycan_involvement": "Specific glycoforms modulate hemoglobin binding.", "mechanism": "Glycosylation variants associated with anemia risk in older adults.", "protein": "Haptoglobin", "protein_enriched": { "function": "As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. 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correlate with vascular calcification.", "protein": "Fetuin-A", "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "medium", "disease": "Cognitive decline", "glycan_involvement": "N-glycosylation at specific sites affects APP cleavage.", "mechanism": "Aberrant glycosylation promotes amyloidogenic processing.", "protein": "Amyloid precursor protein (APP)", "relationship_type": "causal", "source_pmcid": "PMC9735049" }, { "confidence": "high", "disease": "Renal dysfunction", "glycan_involvement": "N-glycosylation required for receptor binding and serum half-life.", "mechanism": "Glycosylation essential for erythropoietin stability and activity in CKD.", "protein": "Erythropoietin", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9735049" }, { "confidence": "medium", "disease": "Frailty", "glycan_involvement": "Glycan changes modulate complement activation.", "mechanism": "Altered C3 glycosylation associated with frailty and immune dysfunction.", "protein": "Complement C3", "protein_enriched": { "function": "Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens a", "gene_name": "C3", "glycan_count": 2, "glycosylation_sites_count": 2, "glytoucan_ids": [ "G80920RR", "G49108TO" ], "uniprot_id": "P01027" }, "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "high", "disease": "Prostate cancer", "glycan_involvement": "Altered O-glycosylation patterns in cancer.", "mechanism": "PSA glycoforms distinguish malignant from benign conditions.", "protein": "Prostate-specific antigen (PSA)", "relationship_type": "biomarker", "source_pmcid": "PMC9735049" }, { "confidence": "medium", "disease": "Purpura Fulminans", "glycan_involvement": "Fibrinogen glycosylation affects clot formation and stability.", "mechanism": "Low fibrinogen levels indicate consumption during microvascular coagulation in PF.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "Purpura Fulminans", "glycan_involvement": "D-dimer is a glycosylated fragment of fibrinogen.", "mechanism": "Elevated D-dimer reflects increased fibrinolysis and ongoing coagulation in PF.", "protein": "D-dimer (fibrin degradation product)", "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Glycosylation modulates fibrinogen function in coagulation.", "mechanism": "Decreased fibrinogen is a diagnostic marker for DIC.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "Disseminated Intravascular Coagulation (DIC)", "glycan_involvement": "Glycosylation status may affect D-dimer clearance.", "mechanism": "High D-dimer indicates excessive clot breakdown in DIC.", "protein": "D-dimer (fibrin degradation product)", "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "Invasive Streptococcus pneumoniae infection", "glycan_involvement": "IgG glycosylation modulates immune effector functions.", "mechanism": "IVIG (pooled IgG) used as adjunctive therapy for severe infection.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "IgA vasculitis", "glycan_involvement": "Aberrant glycosylation of IgA is implicated in pathogenesis.", "mechanism": "IgA deposition is characteristic of IgA vasculitis.", "protein": "Immunoglobulin A (IgA)", "protein_enriched": { "function": "Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral i", "gene_name": "IGHA1", "glycan_count": 148, "glycosylation_sites_count": 11, "glytoucan_ids": [ "G46524LG", "G47681UP", "G57321FI", "G60145BJ", "G29931IJ", "G76355TG", "G81295CK", "G79568CQ", "G00031MO", "G27391WQ", "G29063QY", "G29068FM", "G43417UB", "G53434XO", "G58001LT", "G73004SD", "G88713AC", "G46252BF", "G74722FL", "G31936TA", "G00912UN", "G01650EU", "G02030ZB", "G02815KT", "G03382KH", "G03842KQ", "G05724UK", "G06110VR", "G06356OH", "G08293MJ", "G09862LV", "G10486CT", "G14669DU", "G22140GZ", "G22310AV", "G23294PN", "G23432EQ", "G24835MQ", "G26123CC", "G26403SG", "G27947YN", "G31852PQ", "G31916IQ", "G33609NS", "G36670VW", "G37399XV", "G37868ZX", "G39188ZX", "G40734VV", "G40926MX", "G42358LZ", "G42962KI", "G43157UW", "G44215PV", "G45504EY", "G45841FE", "G46902YN", "G48414YA", "G49955PK", "G50045TK", "G52527GH", "G55052CN", "G55220VL", "G56284ZY", "G59536GA", "G59626AS", "G62765YT", "G64527OM", "G65184UU", "G66676MI", "G66760KM", "G70101JE", "G72291OX", "G72790NZ", "G72797UR", "G80966KZ", "G82020ZR", "G82463GQ", "G83646BJ", "G84452RH", "G86182NS", "G88374WZ", "G95865ZB", "G49108TO", "G00033MO", "G00979XR", "G01614ZM", "G04114CX", "G04765GH", "G05850WN", "G08146BT", "G10256JP", "G12616PJ", "G13863XN", "G16276PY", "G20425TQ", "G23453IV", "G23863VK", "G24363HJ", "G25140TA", "G25278BX", "G25520XG", "G25538MM", "G27248RA", "G29857RC", "G31685JQ", "G32550BI", "G33508VK", "G33780DA", "G34100DU", "G36131WL", "G36191CD", "G39523KI", "G39619TI", "G45495MK", "G46687AB", "G46748BU", "G49854OS", "G50779LX", "G52706RS", "G54499HR", "G54896JZ", "G56682BC", "G56749GV", "G57818FI", "G59658KK", "G60067UC", "G61937QU", "G63628AV", "G64206XB", "G64973KT", "G65219TP", "G65562ZE", "G66419SM", "G68008QO", "G70783BY", "G71306LD", "G75798PH", "G77477NL", "G77550KK", "G78059CC", "G81006GJ", "G91473PK", "G91636VS", "G92129PT", "G94514IB", "G94854LT", "G98535LH" ], "uniprot_id": "P01876" }, "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "low", "disease": "Purpura Fulminans", "glycan_involvement": "Complement glycosylation affects activation and clearance.", "mechanism": "Complement levels checked to rule out deficiency as a risk factor for PF.", "protein": "Complement proteins", "relationship_type": "biomarker", "source_pmcid": "PMC9752976" }, { "confidence": "medium", "disease": "SARS-CoV-2 encephalopathy", "glycan_involvement": "Heavily glycosylated spike mediates host cell binding and immune evasion.", "mechanism": "Spike glycoprotein binds ACE2 receptor, enabling viral entry and potential CNS invasion.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9762911" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycans shield epitopes and modulate infectivity.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9762911" }, { "confidence": "high", "disease": "Cytokine storm", "glycan_involvement": "IL-6R is a glycoprotein; glycosylation affects receptor stability and function.", "mechanism": "IL-6R mediates pro-inflammatory signaling; blockade reduces cytokine storm.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9762911" }, { "confidence": "high", "disease": "SARS-CoV-2 encephalopathy", "glycan_involvement": "Glycosylation may influence receptor-antibody interaction.", "mechanism": "Targeted by tocilizumab to suppress neuroinflammation in encephalopathy.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9762911" }, { "confidence": "medium", "disease": "SARS-CoV-2 encephalopathy", "glycan_involvement": "Fc glycosylation modulates anti-inflammatory activity.", "mechanism": "IVIG used to modulate immune response and reduce neuroinflammation.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9762911" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Glycans modulate immune recognition and viral persistence.", "mechanism": "Spike-induced infection triggers immune dysregulation and cytokine release.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9762911" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects receptor function and antibody binding.", "mechanism": "IL-6R blockade (tocilizumab) reduces severity of COVID-19.", "protein": "Interleukin-6 receptor (IL-6R)", "protein_enriched": { "function": "Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to ", "gene_name": "IL6R", "glycan_count": 6, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G49108TO", "G31218GY", "G57321FI", "G43417UB", "G53434XO", "G83460ZZ" ], "uniprot_id": "P08887" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9762911" }, { "confidence": "high", "disease": "ovarian dysfunction/infertility", "glycan_involvement": "Glycosylation is essential for eCG's stability and bioactivity.", "mechanism": "eCG is used for ovarian stimulation in ruminants due to its FSH and LH activity.", "protein": "equine chorionic gonadotropin (eCG)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9771672" }, { "confidence": "high", "disease": "Cancer", "glycan_involvement": "Glycosylation may affect p53 stability and localization.", "mechanism": "Loss of p53 function leads to impaired DNA damage response and cell cycle arrest.", "protein": "p53", "protein_enriched": { "function": "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775", "gene_name": "TP53", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P04637" }, "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "high", "disease": "Thrombosis", "glycan_involvement": "Glycosylation regulates PAI activity and clearance.", "mechanism": "PAI inhibits fibrinolysis, promoting clot formation.", "protein": "Plasminogen Activator Inhibitor (PAI)", "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "medium", "disease": "Drug toxicity", "glycan_involvement": "Glycosylation modulates enzyme stability and substrate specificity.", "mechanism": "Altered P450 activity affects drug metabolism and detoxification.", "protein": "Cytochrome P450 enzymes", "relationship_type": "biomarker", "source_pmcid": "PMC9771673" }, { "confidence": "high", "disease": "Pancreatitis", "glycan_involvement": "Glycosylation required for inhibitor function.", "mechanism": "Inhibits premature activation of trypsin, preventing autodigestion.", "protein": "Trypsin Inhibitor", "relationship_type": "protective", "source_pmcid": "PMC9771673" }, { "confidence": "high", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation affects insulin secretion and receptor binding.", "mechanism": "Deficiency or resistance leads to hyperglycemia.", "protein": "Insulin", "protein_enriched": { "function": "Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synt", "gene_name": "INS", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P01308" }, "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "medium", "disease": "Exocrine Pancreatic Insufficiency", "glycan_involvement": "Glycosylation modulates hormone stability.", "mechanism": "Altered levels reflect islet cell dysfunction.", "protein": "Pancreatic Polypeptide", "relationship_type": "biomarker", "source_pmcid": "PMC9771673" }, { "confidence": "high", "disease": "Neonatal Hemorrhagic Diathesis (Bleeding Calf Syndrome)", "glycan_involvement": "Glycosylation determines antigenicity and immune recognition.", "mechanism": "Alloantibodies against MHC I cause thrombocytopenia and hemorrhage.", "protein": "Major Histocompatibility Complex Class I", "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "medium", "disease": "Panleukopenia", "glycan_involvement": "Glycosylation essential for antimicrobial activity.", "mechanism": "Secretion of antimicrobial glycoproteins protects intestinal mucosa.", "protein": "Paneth Cell Secretory Proteins", "relationship_type": "protective", "source_pmcid": "PMC9771673" }, { "confidence": "medium", "disease": "Diabetes Mellitus", "glycan_involvement": "Glycosylation affects hormone secretion.", "mechanism": "Excess glucagon contributes to hyperglycemia.", "protein": "Glucagon", "protein_enriched": { "function": "Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose l", "gene_name": "Gcg", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P55095" }, "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "medium", "disease": "Rheumatoid Arthritis", "glycan_involvement": "Aberrant glycosylation promotes inflammation and tissue destruction.", "mechanism": "Glycoprotein-rich pannus tissue invades cartilage and bone.", "protein": "Pannus (synovial glycoproteins)", "relationship_type": "causal", "source_pmcid": "PMC9771673" }, { "confidence": "high", "disease": "von Willebrand disease", "glycan_involvement": "Glycosylation affects stability and function.", "mechanism": "Deficiency or dysfunction leads to impaired platelet adhesion and bleeding.", "protein": "von Willebrand antigen", "relationship_type": "biomarker", "source_pmcid": "PMC9771674" }, { "confidence": "high", "disease": "mesangiocapillary glomerulonephritis", "glycan_involvement": "Glycosylation modulates regulatory activity.", "mechanism": "Regulates complement activation; dysfunction leads to glomerular injury.", "protein": "complement factor H", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "mesangiocapillary glomerulonephritis", "glycan_involvement": "Glycosylation may affect autoantibody binding.", "mechanism": "Autoantibody stabilizes C3 convertase, causing persistent complement activation.", "protein": "C3 nephritic factor", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "partial lipodystrophy", "glycan_involvement": "Glycosylation may affect autoantibody binding.", "mechanism": "Persistent complement activation damages adipose tissue.", "protein": "C3 nephritic factor", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "high", "disease": "systemic lupus erythematosus", "glycan_involvement": "Glycosylation influences antibody effector function.", "mechanism": "Autoantibody against nuclear antigens; diagnostic for SLE.", "protein": "LE factor (antinuclear antibody)", "relationship_type": "biomarker", "source_pmcid": "PMC9771674" }, { "confidence": "high", "disease": "autoimmune hemolytic anemia", "glycan_involvement": "Fc glycosylation modulates effector function.", "mechanism": "IgG autoantibodies target erythrocytes for destruction.", "protein": "immunoglobulin G (IgG)", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "immune complex glomerulonephritis", "glycan_involvement": "Glycosylation affects complement activation.", "mechanism": "Participates in alternate complement pathway; excessive activation damages glomeruli.", "protein": "complement factor B", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "inflammatory diseases", "glycan_involvement": "Glycosylation required for membrane localization.", "mechanism": "Inhibits complement-mediated cell lysis; deficiency increases inflammation.", "protein": "CD59 (homologous restriction factor)", "relationship_type": "protective", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "thymic immunodeficiency", "glycan_involvement": "Glycosylation required for biological activity.", "mechanism": "Low levels indicate thymic dysfunction and immune deficiency.", "protein": "thymulin (facteur thymique s\u00e9rique)", "relationship_type": "biomarker", "source_pmcid": "PMC9771674" }, { "confidence": "medium", "disease": "inflammatory diseases", "glycan_involvement": "Glycosylation modulates receptor binding.", "mechanism": "Promotes platelet aggregation and inflammation.", "protein": "platelet-activating factor (PAF)", "relationship_type": "causal", "source_pmcid": "PMC9771674" }, { "confidence": "high", "disease": "Inherited C3 deficiency", "glycan_involvement": "C3 is a glycoprotein; glycosylation is essential for stability and function.", "mechanism": "Deficiency impairs complement activation, leading to increased susceptibility to infections.", "protein": "C3", "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "Systemic inflammation", "glycan_involvement": "CRP is glycosylated; glycosylation affects its solubility and immune interactions.", "mechanism": "CRP levels rise in response to IL-6 during inflammation.", "protein": "C-reactive protein (CRP)", "protein_enriched": { "function": "Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphory", "gene_name": "CRP", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P02741" }, "relationship_type": "biomarker", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "Autoimmune disease", "glycan_involvement": "N-glycosylation in Fc region modulates effector functions.", "mechanism": "Abnormal Ig glycosylation can alter immune responses and promote autoimmunity.", "protein": "Immunoglobulins", "relationship_type": "causal/biomarker", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "Hereditary angioedema", "glycan_involvement": "Glycosylation required for secretion and activity.", "mechanism": "Deficiency leads to uncontrolled complement activation and angioedema.", "protein": "C1-inactivator (C1 inhibitor)", "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "Wilson's disease", "glycan_involvement": "Glycosylation affects stability and copper binding.", "mechanism": "Low ceruloplasmin levels indicate copper metabolism disorder.", "protein": "Ceruloplasmin", "protein_enriched": { "function": "Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran", "gene_name": "CP", "glycan_count": 229, "glycosylation_sites_count": 6, "glytoucan_ids": [ "G57321FI", "G00912UN", "G01485JJ", "G01650EU", "G02815KT", "G03596YS", "G04657PL", "G04854VP", "G05049YU", "G05933EN", "G06247RL", "G06356OH", "G07246CJ", "G07799LX", "G08146BT", "G08290VR", "G08293MJ", "G08918WF", "G10486CT", "G10819WX", "G11115RO", "G11314AS", "G11629QQ", "G11870QZ", "G11911BT", "G12793SR", "G14972EH", "G15169WU", "G15664MX", "G17208MA", "G18647XP", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G23719VF", "G23863VK", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27915IV", "G27947YN", "G28541PG", "G31118FR", "G31852PQ", "G31916IQ", "G34989PA", "G35029YA", "G36379GD", "G37399XV", "G37509XX", "G37818NZ", "G37868ZX", "G39446WN", "G39595FH", "G40574BA", "G40834TG", "G40926MX", "G41044JW", "G41071NU", "G41247ZX", "G42124LM", "G42358LZ", "G43223CG", "G43669FQ", "G45395BF", "G45495MK", "G45504EY", "G47518TP", "G47644PP", "G47737VJ", "G48414YA", "G50045TK", "G50282JC", "G51413EV", "G52527GH", "G53075ES", "G56518TU", "G56749GV", "G57317CE", "G57776ZS", "G57776ZU", "G59324HL", "G59536GA", "G59626AS", "G60033FS", "G60834IK", "G61256FT", "G62765YT", "G63041LO", "G63980BQ", "G65414LI", "G66665YI", "G69834CE", "G70223PD", "G70232NH", "G70441OD", "G70619PT", "G70822IO", "G70888PK", "G71146HJ", "G72580QS", "G72747WU", "G72787SB", "G72791KH", "G74772YG", "G75983OB", "G76295SF", "G76417NN", "G77547TA", "G77669RF", "G78787DI", "G79666IR", "G80075MS", "G80920RR", "G81198YO", "G81263BG", "G82830MN", "G83460ZZ", "G83555HU", "G83633GK", "G83646BJ", "G84452RH", "G84467IZ", "G85144OK", "G85269DF", "G86182NS", "G86752LQ", "G86795LJ", "G86880BF", "G87123QX", "G87661QW", "G88374WZ", "G88891KO", "G89877QI", "G90382BL", "G90575OW", "G90659AW", "G92135MA", "G92275SC", "G92551JA", "G94470IW", "G94917XT", "G95177YH", "G95678HJ", "G95865ZB", "G96091TT", "G98611JV", "G99679NM", "G00273SJ", "G02528FI", "G10846ZT", "G14547CB", "G28681TP", "G31986NC", "G36442WJ", "G37692EO", "G42962KI", "G44211QA", "G44215PV", "G46691LC", "G46902YN", "G51640FO", "G58087IP", "G58954YZ", "G68490OW", "G69521XL", "G72197KC", "G80479JV", "G81124ET", "G85282JO", "G89098OM", "G92081HT", "G99668VU", "G46524LG", "G10019LZ", "G15038BD", "G23010ZW", "G33791AF", "G37412TK", "G37881RL", "G47748JZ", "G47950XN", "G55412XP", "G67895PX", "G86500WE", "G88619MM", "G95977AE", "G43417UB", "G02030ZB", "G02886BB", "G05962QB", "G07810QS", "G11101UV", "G12341GU", "G13910DJ", "G16125XL", "G16136DL", "G20312EM", "G28622IK", "G30221QT", "G30248BL", "G30740WO", "G31596VW", "G32788FZ", "G32926LW", "G33416PL", "G36670VW", "G37995HC", "G41840AI", "G49018RC", "G49755GI", "G50856PC", "G55132BD", "G57888GL", "G64394MX", "G66933CM", "G72291OX", "G77459ND", "G80669SJ", "G81637OR", "G82443XX", "G85554PZ", "G89827JR", "G91473PK", "G94665LC", "G98129XB", "G49108TO" ], "uniprot_id": "P00450" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9771676" }, { "confidence": "medium", "disease": "Calcium malabsorption disorders", "glycan_involvement": "Glycosylation may affect protein stability and localization.", "mechanism": "Calbindin facilitates calcium absorption; deficiency leads to hypocalcemia.", "protein": "Calbindin", "protein_enriched": { "function": "Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase", "gene_name": "Calb1", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G50282JC" ], "uniprot_id": "P12658" }, "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "medium", "disease": "Cancer", "glycan_involvement": "Glycosylation modulates cell-cell adhesion and signaling.", "mechanism": "Loss of cadherin-mediated adhesion promotes metastasis.", "protein": "Cadherins", "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "Calicivirus infection (cats, rabbits, pigs)", "glycan_involvement": "Glycosylation shields viral epitopes from host immunity.", "mechanism": "Viral glycoprotein mediates host cell entry and immune evasion.", "protein": "Calicivirus major capsid protein", "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "medium", "disease": "Chronic oral lesions (cats)", "glycan_involvement": "Glycosylation may affect viral persistence and immune response.", "mechanism": "Persistent infection leads to chronic oral inflammation.", "protein": "Calicivirus major capsid protein", "relationship_type": "causal", "source_pmcid": "PMC9771676" }, { "confidence": "low", "disease": "Feline lower urinary tract disease", "glycan_involvement": "Potential role in tissue tropism and immune evasion.", "mechanism": "Association observed; mechanism unclear.", "protein": "Calicivirus major capsid protein", "relationship_type": "possible causal", "source_pmcid": "PMC9771676" }, { "confidence": "high", "disease": "urolithiasis", "glycan_involvement": "Heavily glycosylated; glycan chains mediate interaction with urinary solutes", "mechanism": "Principal constituent of urinary casts; may modulate crystal formation", "protein": "Tamm\u2013Horsfall mucoprotein", "relationship_type": "causal/protective", "source_pmcid": "PMC9771678" }, { "confidence": "high", "disease": "tumors/cancer", "glycan_involvement": "Aberrant glycosylation patterns (e.g., Tn, sialyl-Tn antigens)", "mechanism": "Expressed on tumor cells; recognized by immune system", "protein": "Tumor antigen (T antigen)", "relationship_type": "biomarker", "source_pmcid": "PMC9771678" }, { "confidence": "high", "disease": "tumors/cancer", "glycan_involvement": "Altered glycosylation increases immunogenicity", "mechanism": "Overexpressed or altered glycoproteins in cancer", "protein": "Tumor-associated antigen (TAA)", "relationship_type": "biomarker/therapeutic_target", "source_pmcid": "PMC9771678" }, { "confidence": "high", "disease": "thrombotic disease", "glycan_involvement": "N-glycosylation affects plasma half-life and activity", "mechanism": "Promotes fibrinolysis; used to treat thrombosis", "protein": "tissue plasminogen activator (t-PA)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9771678" }, { "confidence": "medium", "disease": "meibomian adenitis", "glycan_involvement": "Glycosylation critical for secretion and stability", "mechanism": "Secreted glycoproteins contribute to tear film; inflammation disrupts function", "protein": "Meibomian gland glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC9771678" }, { "confidence": "medium", "disease": "autoimmune disease", "glycan_involvement": "N-glycosylation modulates receptor function", "mechanism": "Aberrant TCR glycosylation may alter antigen recognition", "protein": "T cell receptor", "relationship_type": "causal", "source_pmcid": "PMC9771678" }, { "confidence": "medium", "disease": "transplant rejection", "glycan_involvement": "Glycosylation may affect protein stability", "mechanism": "Targeted by tacrolimus to suppress immune response", "protein": "FK-binding proteins (FKBP)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9771678" }, { "confidence": "medium", "disease": "inflammatory and immune-mediated skin diseases", "glycan_involvement": "Glycosylation modulates cell-cell interactions", "mechanism": "NK cell glycoproteins mediate cytotoxicity in immune skin diseases", "protein": "Natural killer cell surface glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC9771678" }, { "confidence": "low", "disease": "taste disorders", "glycan_involvement": "N-glycosylation required for proper receptor folding and function", "mechanism": "Altered glycosylation may impair taste receptor function", "protein": "Taste receptor glycoproteins", "relationship_type": "causal", "source_pmcid": "PMC9771678" }, { "confidence": "high", "disease": "urolithiasis", "glycan_involvement": "Glycan chains mediate anti-adhesive properties", "mechanism": "Prevents crystal aggregation in urine", "protein": "Tamm\u2013Horsfall protein (uromodulin)", "relationship_type": "protective", "source_pmcid": "PMC9771678" }, { "confidence": "high", "disease": "Complement-mediated diseases", "glycan_involvement": "Glycosylation is required for DAF's membrane localization and function.", "mechanism": "DAF prevents assembly or accelerates disassembly of C3 convertase, down-regulating complement activity and protecting cells from complement-mediated lysis.", "protein": "Decay-accelerating factor (DAF)", "relationship_type": "protective", "source_pmcid": "PMC9771679" }, { "confidence": "high", "disease": "Type III glycogen storage disease", "glycan_involvement": "Enzyme is a glycoprotein; glycosylation may affect stability and activity.", "mechanism": "Deficiency of debrancher enzyme leads to accumulation of abnormal glycogen in tissues.", "protein": "Debrancher enzyme", "protein_enriched": { "function": "The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or ", "gene_name": "TAF2", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q6P1X5" }, "relationship_type": "causal", "source_pmcid": "PMC9771679" }, { "confidence": "medium", "disease": "Bone/connective tissue disorders", "glycan_involvement": "Chondroitin sulfate glycosylation is essential for decorin's structural role.", "mechanism": "Decorin is involved in organization and mineralization of bone; defects may contribute to connective tissue and bone disorders.", "protein": "Decorin", "relationship_type": "causal/biomarker", "source_pmcid": "PMC9771679" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "A\u03b2 is a glycoprotein; glycosylation may affect aggregation and clearance.", "mechanism": "A\u03b2 aggregation forms amyloid plaques, triggers neuroinflammation and neurodegeneration.", "protein": "Amyloid beta (A\u03b2)", "relationship_type": "causal", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "Parkinson's disease", "glycan_involvement": "Glycosylation may modulate aggregation and toxicity.", "mechanism": "Aggregation into Lewy bodies, microglial activation, and neurodegeneration.", "protein": "Alpha-synuclein (\u03b1-syn)", "relationship_type": "causal", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "Tau is glycosylated; glycosylation may influence aggregation.", "mechanism": "Hyperphosphorylated tau forms neurofibrillary tangles, contributing to neurodegeneration.", "protein": "Tau protein (\u03c4)", "relationship_type": "causal", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "GFAP is a glycoprotein; glycosylation may affect stability and detection.", "mechanism": "Elevated plasma GFAP reflects reactive astrogliosis and correlates with disease severity.", "protein": "GFAP", "protein_enriched": { "function": "GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells", "gene_name": "GFAP", "glycan_count": 1, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "P14136" }, "relationship_type": "biomarker", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "Alzheimer's disease", "glycan_involvement": "APOE is glycosylated; glycosylation may affect lipid binding and immune interactions.", "mechanism": "APOE4 genotype increases risk, especially with HSV-1 reactivation.", "protein": "APOE", "relationship_type": "causal/risk factor", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "Multiple sclerosis", "glycan_involvement": "HLA II are glycoproteins; glycosylation affects antigen presentation.", "mechanism": "Certain HLA II alleles (e.g., DRB1*1501) increase susceptibility, especially with viral infections.", "protein": "HLA class II", "relationship_type": "causal/risk factor", "source_pmcid": "PMC9774074" }, { "confidence": "medium", "disease": "Alzheimer's disease", "glycan_involvement": "LRP1 is a glycoprotein; glycosylation is essential for function.", "mechanism": "LRP1 mediates A\u03b2 clearance; reduced LRP1 impairs A\u03b2 removal.", "protein": "LRP1", "relationship_type": "protective", "source_pmcid": "PMC9774074" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Transferrin is N-glycosylated; glycosylation affects iron binding and transport.", "mechanism": "Transferrin in oligodendrocytes involved in iron homeostasis; dysregulation linked to PD.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9774074" }, { "confidence": "medium", "disease": "Parkinson's disease", "glycan_involvement": "Ferritin is glycosylated; glycosylation may affect stability and iron storage.", "mechanism": "Altered ferritin levels in microglia/astrocytes linked to iron toxicity and neurodegeneration.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker/causal", "source_pmcid": "PMC9774074" }, { "confidence": "medium", "disease": "COVID-19 neurological complications", "glycan_involvement": "CD147 is heavily glycosylated; glycosylation is critical for viral binding.", "mechanism": "CD147 acts as a SARS-CoV-2 entry receptor in CNS, facilitating neuroinvasion.", "protein": "CD147 (EMMPRIN)", "relationship_type": "causal/entry receptor", "source_pmcid": "PMC9774074" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan shield modulates immune evasion and infectivity.", "mechanism": "Spike glycoprotein mediates viral entry into host cells via ACE2 receptor.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Glycosylation affects serum stability and detection.", "mechanism": "Elevated CK-MB indicates cardiac injury/inflammation in severe COVID-19 cases.", "protein": "CK-MB (Creatine Kinase-MB)", "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "N-glycosylation modulates CRP function and clearance.", "mechanism": "CRP elevation reflects systemic inflammation in COVID-19.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Glycosylation influences LDH serum half-life.", "mechanism": "Elevated LDH correlates with tissue damage and disease severity.", "protein": "LDH (Lactate Dehydrogenase)", "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Glycosylation of fibrin fragments affects immunodetection.", "mechanism": "Elevated D-dimer indicates hypercoagulable state in severe COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Glycosylation modulates ferritin secretion and immune recognition.", "mechanism": "High ferritin reflects hyperinflammation and disease severity.", "protein": "Ferritin", "protein_enriched": { "function": "Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd", "gene_name": "FTH1", "glycan_count": 3, "glycosylation_sites_count": 0, "glytoucan_ids": [ "G80920RR", "G83460ZZ", "G49108TO" ], "uniprot_id": "P02794" }, "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Glycosylation impacts troponin stability and detection.", "mechanism": "Elevated troponin suggests cardiac involvement in severe cases.", "protein": "Troponin", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "Pediatric COVID-19 pneumonia", "glycan_involvement": "Conjugation to glycoproteins facilitates hepatic clearance.", "mechanism": "Elevated direct bilirubin correlates with severe disease.", "protein": "Direct Bilirubin", "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation modulates cell-cell interactions and immune signaling.", "mechanism": "Altered leukocyte counts (leukopenia/leukocytosis) reflect immune response.", "protein": "Leukocyte surface glycoproteins", "relationship_type": "biomarker", "source_pmcid": "PMC9809511" }, { "confidence": "high", "disease": "Glanzmann Disease", "glycan_involvement": "Glycosylation required for proper folding and platelet aggregation.", "mechanism": "Deficiency/mutation in platelet glycoprotein IIb/IIIa causes bleeding disorder.", "protein": "Glanzmann glycoprotein IIb/IIIa", "relationship_type": "causal", "source_pmcid": "PMC9809511" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike protein modulates receptor binding and immune evasion.", "mechanism": "Spike glycoprotein binds ACE2 to mediate viral entry and infection.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "ACE2 glycosylation affects spike binding affinity.", "mechanism": "ACE2 is the primary receptor for SARS-CoV-2 entry; viral binding reduces ACE2 activity.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycan structures may influence spike interaction.", "mechanism": "CD147 acts as an alternative receptor facilitating SARS-CoV-2 entry.", "protein": "CD147 (Basigin/EMMPRIN)", "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect spike-NRP1 interaction.", "mechanism": "NRP1 enhances SARS-CoV-2 cell entry and tissue tropism.", "protein": "Neuropilin-1 (NRP1)", "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "high", "disease": "Thromboembolism", "glycan_involvement": "vWF glycosylation regulates multimerization and function.", "mechanism": "Elevated vWF levels indicate endothelial activation and coagulopathy in COVID-19.", "protein": "von Willebrand Factor (vWF)", "relationship_type": "biomarker", "source_pmcid": "PMC9843681" }, { "confidence": "high", "disease": "Hypertension", "glycan_involvement": "Glycosylation may affect ACE2 stability and activity.", "mechanism": "ACE2 counteracts RAS-mediated vasoconstriction; reduced ACE2 linked to hypertension.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "protective", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "Diabetes mellitus", "glycan_involvement": "Glycosylation may modulate ACE2 localization in islets.", "mechanism": "ACE2 expressed in pancreatic beta cells; SARS-CoV-2 infection may induce new-onset diabetes.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "N-glycosylation required for secretion and function.", "mechanism": "Angiotensinogen is a glycoprotein precursor in RAS; dysregulation contributes to hypertension.", "protein": "Angiotensinogen", "relationship_type": "causal", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "Endothelial dysfunction", "glycan_involvement": "Glycosylation affects cell-cell adhesion properties.", "mechanism": "VE-cadherin is a marker of endothelial activation and injury in COVID-19.", "protein": "VE-cadherin", "relationship_type": "biomarker", "source_pmcid": "PMC9843681" }, { "confidence": "medium", "disease": "COVID-19-associated inflammation", "glycan_involvement": "Glycosylation modulates ligand binding and immune cell interactions.", "mechanism": "Upregulated ICAM-1 reflects endothelial activation and leukocyte recruitment.", "protein": "ICAM-1", "protein_enriched": { "function": "ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical", "gene_name": "ICAM1", "glycan_count": 111, "glycosylation_sites_count": 8, "glytoucan_ids": [ "G05962QB", "G27947YN", "G30740WO", "G40926MX", "G45395BF", "G57776ZS", "G68490OW", "G69521XL", "G79666IR", "G85282JO", "G86880BF", "G07246CJ", "G16125XL", "G37818NZ", "G62765YT", "G78787DI", "G80479JV", "G80920RR", "G93718GY", "G00912UN", "G01160VV", "G01485JJ", "G01650EU", "G02528FI", "G04657PL", "G06247RL", "G08918WF", "G10819WX", "G13131HA", "G14972EH", "G15169WU", "G20528HD", "G24528MX", "G27058EU", "G28622IK", "G29545VG", "G30221QT", "G30970QQ", "G32788FZ", "G35541EV", "G37399XV", "G39471UU", "G40206WX", "G40834TG", "G41071NU", "G43223CG", "G45526EA", "G50856PC", "G53075ES", "G55132BD", "G59924QI", "G60033FS", "G60834IK", "G60967DT", "G65414LI", "G70232NH", "G70441OD", "G70888PK", "G71463BG", "G75568BH", "G76295SF", "G80075MS", "G80669SJ", "G81637OR", "G82443XX", "G83460ZZ", "G85269DF", "G87123QX", "G90382BL", "G92135MA", "G94665LC", "G95046LV", "G59324HL", "G00273SJ", "G02886BB", "G08290VR", "G10486CT", "G11314AS", "G27126ED", "G28541PG", "G29299MO", "G31852PQ", "G40574BA", "G41247ZX", "G41840AI", "G43669FQ", "G46691LC", "G47644PP", "G47702MW", "G47950XN", "G49906RN", "G51653BI", "G58087IP", "G58954YZ", "G59626AS", "G63041LO", "G70619PT", "G72747WU", "G81124ET", "G83646BJ", "G84225JN", "G84862VB", "G87661QW", "G90575OW", "G90659AW", "G92406TI", "G95865ZB", "G96091TT", "G99668VU", "G57321FI", "G49108TO" ], "uniprot_id": "P05362" }, "relationship_type": "biomarker", "source_pmcid": "PMC9843681" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N-glycosylated; glycosylation modulates receptor binding and immune evasion.", "mechanism": "Mediates viral entry by binding to ACE2; essential for infection.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9906121" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of ACE2 affects S protein binding affinity.", "mechanism": "Acts as the main host receptor for SARS-CoV-2 S protein, enabling viral entry.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "SARS", "glycan_involvement": "N-glycosylation modulates receptor interaction.", "mechanism": "S protein mediates entry of SARS-CoV via ACE2.", "protein": "Spike (S) protein", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation required for stability and activity.", "mechanism": "Used as immunomodulator to slow viral replication and enhance anti-inflammatory cytokines.", "protein": "Interferon beta-1a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects pharmacokinetics and efficacy.", "mechanism": "Part of combination therapy to reduce viral shedding and cytokine response.", "protein": "Interferon beta-1b", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc glycosylation modulates effector functions.", "mechanism": "IVIg used to modulate immune response and neutralize virus.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "Cytokine storm", "glycan_involvement": "Therapeutic antibody glycosylation affects efficacy and safety.", "mechanism": "Blocks IL-6 receptor to reduce hyperinflammation in severe COVID-19.", "protein": "Tocilizumab (anti-IL-6R IgG1)", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation may affect assembly and immune recognition.", "mechanism": "Essential for virion assembly and budding.", "protein": "Membrane (M) protein", "protein_enriched": { "function": "Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins (By similarity). Regulates the localization of S protein at", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P0DTC5" }, "relationship_type": "causal", "source_pmcid": "PMC9906121" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation may modulate function.", "mechanism": "Contributes to virion assembly and release.", "protein": "Envelope (E) protein", "protein_enriched": { "function": "Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in", "gene_name": "E", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC4" }, "relationship_type": "causal", "source_pmcid": "PMC9906121" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Binds N-glycans on nascent glycoproteins.", "mechanism": "ER chaperone assists folding of viral glycoproteins (e.g., S protein), influencing viral maturation.", "protein": "Calnexin", "relationship_type": "protective", "source_pmcid": "PMC9906121" }, { "confidence": "high", "disease": "Pandemic Influenza A virus H1N1 pneumonia", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Increased tissue expression correlates with neutrophil recruitment and worse prognosis.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "biomarker", "source_pmcid": "PMC9907201" }, { "confidence": "high", "disease": "Pandemic Influenza A virus H1N1 pneumonia", "glycan_involvement": "IL-17RA is a glycoprotein; glycosylation may affect receptor function.", "mechanism": "Polymorphisms (rs2241044 C allele, rs2241043 T allele) associated with increased risk and worse prognosis.", "protein": "IL-17RA", "relationship_type": "biomarker", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Not glycosylated; no direct glycan involvement.", "mechanism": "Promotes neutrophil chemotaxis and inflammatory damage in lung tissue.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Acute lung injury", "glycan_involvement": "Glycosylation may modulate receptor-ligand interaction and signaling.", "mechanism": "Receptor mediates IL-17A signaling, leading to inflammation and tissue damage.", "protein": "IL-17RA", "relationship_type": "causal", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Rheumatoid arthritis", "glycan_involvement": "Glycosylation may affect receptor stability and function.", "mechanism": "IL-17RA mediates pro-inflammatory signaling in autoimmune pathology.", "protein": "IL-17RA", "relationship_type": "causal", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Non-pandemic acute viral pneumonia", "glycan_involvement": "Not glycosylated.", "mechanism": "Elevated tissue expression in fatal cases.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "biomarker", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Non-pandemic acute viral pneumonia", "glycan_involvement": "Glycosylation may affect receptor function.", "mechanism": "Elevated tissue expression in fatal cases.", "protein": "IL-17RA", "relationship_type": "biomarker", "source_pmcid": "PMC9907201" }, { "confidence": "high", "disease": "Pandemic Influenza A virus H1N1 pneumonia", "glycan_involvement": "Glycosylation may modulate receptor activity.", "mechanism": "Polymorphisms associated with increased susceptibility and earlier death.", "protein": "IL-17RA", "relationship_type": "causal", "source_pmcid": "PMC9907201" }, { "confidence": "high", "disease": "Pandemic Influenza A virus H1N1 pneumonia", "glycan_involvement": "Not glycosylated.", "mechanism": "Polymorphism (rs3819025 A allele) associated with higher expression and worse outcome.", "protein": "IL-17A", "protein_enriched": { "function": "Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor co", "gene_name": "IL17A", "glycan_count": 1, "glycosylation_sites_count": 1, "glytoucan_ids": [ "G49108TO" ], "uniprot_id": "Q16552" }, "relationship_type": "causal", "source_pmcid": "PMC9907201" }, { "confidence": "medium", "disease": "Pandemic Influenza A virus H1N1 pneumonia", "glycan_involvement": "Glycosylation status could influence therapeutic antibody binding.", "mechanism": "Blocking IL-17RA may reduce inflammation and tissue damage.", "protein": "IL-17RA", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9907201" }, { "confidence": "high", "disease": "COVID-19 (severe)", "glycan_involvement": "Spike glycosylation enables LPS binding and immune modulation.", "mechanism": "Spike binds LPS, amplifies TLR4-mediated pro-inflammatory signaling, leading to hyperinflammation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "Glycosylated spike facilitates LPS binding.", "mechanism": "Spike-LPS interaction boosts innate immune activation, increasing risk of sepsis.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "Acute respiratory distress syndrome (ARDS)", "glycan_involvement": "Spike glycosylation is critical for LPS interaction.", "mechanism": "Spike-LPS synergy triggers excessive inflammation, contributing to ARDS.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "medium", "disease": "Diabetes", "glycan_involvement": "Spike glycosylation status may affect disease severity.", "mechanism": "Diabetic patients have elevated LPS, increasing risk of spike-mediated hyperinflammation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9912767" }, { "confidence": "medium", "disease": "Hypertension", "glycan_involvement": "Glycosylation may modulate spike-LPS interaction.", "mechanism": "Hypertensive patients show higher LPS, predisposing to spike-driven inflammation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9912767" }, { "confidence": "medium", "disease": "Obesity", "glycan_involvement": "Spike glycosylation facilitates LPS binding.", "mechanism": "Obese patients have increased LPS, enhancing spike-induced immune activation.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "biomarker", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "CD14 glycosylation is important for LPS binding.", "mechanism": "CD14 transfers LPS to TLR4, initiating inflammatory response.", "protein": "CD14", "protein_enriched": { "function": "Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating th", "gene_name": "CD14", "glycan_count": 51, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G00912UN", "G02402FF", "G05724UK", "G06110VR", "G06356OH", "G10486CT", "G20312EM", "G22140GZ", "G23294PN", "G23863VK", "G31852PQ", "G33609NS", "G37399XV", "G37868ZX", "G39188ZX", "G40926MX", "G42358LZ", "G42962KI", "G44215PV", "G45495MK", "G48414YA", "G50045TK", "G55220VL", "G57776ZU", "G57818FI", "G59626AS", "G62765YT", "G66538GV", "G72291OX", "G72735IY", "G80920RR", "G80966KZ", "G82020ZR", "G82463GQ", "G84452RH", "G84820NF", "G95865ZB", "G02815KT", "G15664MX", "G20706XG", "G30221QT", "G41247ZX", "G46503DX", "G60177UT", "G64527OM", "G66676MI", "G70101JE", "G27391WQ", "G29068FM", "G29931IJ", "G43417UB" ], "uniprot_id": "P08571" }, "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "Sepsis", "glycan_involvement": "TLR4 glycosylation affects ligand recognition.", "mechanism": "TLR4 activation by LPS (and spike) triggers systemic inflammation.", "protein": "Toll-like receptor 4 (TLR4)", "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "medium", "disease": "COVID-19 (severe)", "glycan_involvement": "Altered glycosylation impacts LPS binding.", "mechanism": "Loss of high-affinity LPS binding site in Omicron spike reduces boosting of inflammation.", "protein": "SARS-CoV-2 spike glycoprotein (Omicron variant)", "relationship_type": "protective", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "Gram-negative bacterial coinfection", "glycan_involvement": "Spike glycosylation is essential for LPS interaction.", "mechanism": "Spike acts as a conduit for LPS, exacerbating inflammation during bacterial coinfection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9912767" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation of spike is essential for structural flexibility and effective receptor binding.", "mechanism": "Spike glycoprotein mediates viral entry by binding to host cell receptors, enabling infection.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "causal", "source_pmcid": "PMC9912786" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects antigenicity and accessibility of epitopes.", "mechanism": "Spike glycoprotein is the main target for vaccines, diagnostics, and therapeutic antibodies.", "protein": "SARS-CoV-2 spike glycoprotein", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9912786" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily glycosylated; glycosylation modulates antigenicity and immune recognition.", "mechanism": "Target of IgM/IgG antibodies; cross-reactivity may affect serodiagnosis and immunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Glycosylation affects immune recognition.", "mechanism": "Target of IgM/IgG antibodies; cross-reactivity may affect serodiagnosis and immunity.", "protein": "SARS-CoV-2 Nucleocapsid protein", "protein_enriched": { "function": "Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane prot", "gene_name": "N", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P0DTC9" }, "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "medium", "disease": "Common cold", "glycan_involvement": "Shared glycan motifs may drive cross-reactivity.", "mechanism": "Cross-reactive antibodies from common cold coronaviruses may confer partial protection against COVID-19.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "protective", "source_pmcid": "PMC9931394" }, { "confidence": "medium", "disease": "Autoimmune diseases", "glycan_involvement": "Glycosylation may influence epitope mimicry.", "mechanism": "Shared peptide motifs with human autoantigens (e.g., myosin-7, mucin-16, filaggrin) may trigger autoimmunity.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9931394" }, { "confidence": "medium", "disease": "Malaria", "glycan_involvement": "Glycosylation of parasite proteins modulates immune response.", "mechanism": "Cross-reactive antibodies to SARS-CoV-2 nucleocapsid peptides share motifs with malaria antigens.", "protein": "Plasmodium falciparum Merozoite Surface Protein", "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "low", "disease": "Herpesvirus infection", "glycan_involvement": "Viral glycoprotein glycosylation affects immunogenicity.", "mechanism": "Shared motifs with SARS-CoV-2 spike protein may induce cross-reactive antibodies.", "protein": "Human betaherpesvirus 6B envelope glycoprotein GP350", "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "low", "disease": "Leprosy", "glycan_involvement": "Bacterial glycosylation may influence immune cross-reactivity.", "mechanism": "Polyprotein 1AB peptides share motifs with bacterial chaperones, suggesting cross-reactivity.", "protein": "Helicobacter pylori Chaperone Protein", "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "low", "disease": "Allergy (Peanut)", "glycan_involvement": "Plant glycoprotein glycosylation modulates allergenicity.", "mechanism": "Polyprotein 1AB peptides share motifs with peanut allergens, possibly influencing allergy responses.", "protein": "Arachis hypogaea (Peanut) Allergen", "relationship_type": "causal", "source_pmcid": "PMC9931394" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Contains glycosylated domains affecting immune recognition.", "mechanism": "Target of cross-reactive IgM/IgG antibodies; may affect serodiagnosis.", "protein": "SARS-CoV-2 Polyprotein 1AB", "relationship_type": "biomarker", "source_pmcid": "PMC9931394" }, { "confidence": "low", "disease": "Autoimmune diseases", "glycan_involvement": "Heavily glycosylated; glycan structures may influence epitope mimicry.", "mechanism": "Shared motifs with SARS-CoV-2 nucleocapsid peptides may trigger autoimmunity.", "protein": "Human Mucin-16", "relationship_type": "causal", "source_pmcid": "PMC9931394" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation required for proper folding, function, and immune evasion", "mechanism": "Mediates viral entry via ACE2 binding; essential for infection", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9969538" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of subunit 2 critical for function; tunicamycin inhibits its synthesis", "mechanism": "Structural component required for virion assembly and release", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects antigenicity; tunicamycin reduces glycosylation and antigenicity", "mechanism": "Major structural protein for virion assembly", "protein": "Membrane glycoprotein (M)", "relationship_type": "causal", "source_pmcid": "PMC9969538" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation required for spike formation; inhibition blocks infectivity", "mechanism": "Tunicamycin inhibits N-glycosylation, leading to spikeless, non-infectious virions", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969538" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of E protein subunit 2 is tunicamycin-sensitive", "mechanism": "Tunicamycin suppresses production of glycosylated E protein subunit 2", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Glycosylation status may affect ORF8 function; tunicamycin binding may disrupt activity", "mechanism": "Tunicamycin binds ORF8, potentially affecting its function", "protein": "ORF8", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Potential glycosylation involvement; tunicamycin may disrupt function", "mechanism": "Tunicamycin binds ORF3a, possibly altering its activity", "protein": "ORF3a", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Not directly glycosylated, but binding may affect viral protein maturation", "mechanism": "Tunicamycin binds with high affinity, potentially inhibiting protease activity", "protein": "Proteinase 3CLpro", "relationship_type": "therapeutic_target", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation patterns serve as biomarkers for viral maturation", "mechanism": "Glycosylation status of spike can indicate viral infectivity and immune evasion", "protein": "Spike glycoprotein (S)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9969538" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of E protein as a marker for virion production", "mechanism": "Glycosylation status of E protein reflects viral assembly and release efficiency", "protein": "Envelope glycoprotein (E)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9969538" }, { "confidence": "high", "disease": "Atherosclerosis", "glycan_involvement": "LDL is a glycoprotein; glycosylation affects its recognition and clearance.", "mechanism": "Oxidized LDL accumulates in vessel walls, triggering inflammation and plaque formation.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC9975876" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "Glycosylation status can modulate LDL metabolism.", "mechanism": "Elevated LDL is a hallmark of hyperlipidemia.", "protein": "LDL", "relationship_type": "biomarker", "source_pmcid": "PMC9975876" }, { "confidence": "high", "disease": "Hyperlipidemia", "glycan_involvement": "VLDL is glycosylated, influencing its plasma half-life.", "mechanism": "Increased VLDL levels indicate disrupted lipid metabolism.", "protein": "VLDL", "relationship_type": "biomarker", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Atherosclerosis", "glycan_involvement": "HDL glycosylation modulates its anti-atherogenic functions.", "mechanism": "HDL facilitates reverse cholesterol transport, reducing plaque formation.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "AST is glycosylated, which may affect its stability and serum levels.", "mechanism": "Elevated AST indicates liver cell injury due to fat accumulation.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Non-alcoholic fatty liver disease", "glycan_involvement": "ALT glycosylation may influence its secretion and activity.", "mechanism": "ALT elevation reflects hepatocellular damage from lipid overload.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Liver disease", "glycan_involvement": "ALP glycosylation affects its isoform distribution and diagnostic value.", "mechanism": "ALP increases with liver dysfunction and cholestasis.", "protein": "ALP", "relationship_type": "biomarker", "source_pmcid": "PMC9975876" }, { "confidence": "high", "disease": "Cardiovascular disease", "glycan_involvement": "Glycosylation modulates LDL receptor binding and clearance.", "mechanism": "High LDL promotes vascular inflammation and atherogenesis.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Kidney disease", "glycan_involvement": "Glycosylation may affect LDL deposition in renal tissue.", "mechanism": "LDL accumulation contributes to glomerular injury and inflammation.", "protein": "LDL", "relationship_type": "causal", "source_pmcid": "PMC9975876" }, { "confidence": "medium", "disease": "Cardiovascular disease", "glycan_involvement": "HDL glycosylation influences its anti-inflammatory properties.", "mechanism": "Higher HDL levels are associated with reduced cardiovascular risk.", "protein": "HDL", "relationship_type": "protective", "source_pmcid": "PMC9975876" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "N-glycosylation of ACE2 modulates viral binding affinity.", "mechanism": "ACE2 is the entry receptor for SARS-CoV-2, mediating viral infection.", "protein": "ACE2", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9984757" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "Heavily N- and O-glycosylated; glycans shield epitopes and affect immune recognition.", "mechanism": "Spike protein binds ACE2 to mediate viral entry.", "protein": "SARS-CoV-2 Spike protein", "relationship_type": "causal", "source_pmcid": "PMC9984757" }, { "confidence": "high", "disease": "COVID-19", "glycan_involvement": "CRP is N-glycosylated, affecting its stability and function.", "mechanism": "Elevated CRP correlates with severe COVID-19 and mortality.", "protein": "CRP (C-reactive protein)", "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "LDH is glycosylated, which may influence serum levels.", "mechanism": "Elevated LDH is associated with severe disease and mortality.", "protein": "LDH (Lactate dehydrogenase)", "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "high", "disease": "Coagulopathy", "glycan_involvement": "D-dimer is a glycoprotein fragment; glycosylation affects clearance.", "mechanism": "Elevated D-dimer indicates disseminated intravascular coagulation in severe COVID-19.", "protein": "D-dimer", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "ALT is glycosylated, influencing secretion and stability.", "mechanism": "Elevated ALT is a marker of liver injury in COVID-19.", "protein": "ALT", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "medium", "disease": "Liver injury", "glycan_involvement": "AST is glycosylated, influencing secretion and stability.", "mechanism": "Elevated AST is a marker of liver injury in COVID-19.", "protein": "AST", "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "medium", "disease": "COVID-19", "glycan_involvement": "Fc N-glycosylation modulates effector function and inflammation.", "mechanism": "IgG response is used to monitor infection and immunity.", "protein": "Immunoglobulin G (IgG)", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "low", "disease": "COVID-19", "glycan_involvement": "N-glycosylation affects half-life and function.", "mechanism": "Altered transferrin levels reflect inflammation and iron metabolism in COVID-19.", "protein": "Transferrin", "protein_enriched": { "function": "Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites", "gene_name": "TF", "glycan_count": 297, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G29068FM", "G00912UN", "G01650EU", "G02815KT", "G02886BB", "G03596YS", "G04055MU", "G04657PL", "G04854VP", "G04909DG", "G05962QB", "G06247RL", "G06356OH", "G07246CJ", "G07810QS", "G08110WX", "G08293MJ", "G08918WF", "G09831WQ", "G10486CT", "G10819WX", "G10846ZT", "G11101UV", "G11115RO", "G11314AS", "G11629QQ", "G11911BT", "G12341GU", "G12579WK", "G14547CB", "G14994KB", "G15038BD", "G15508AW", "G15664MX", "G16125XL", "G17168RO", "G18647XP", "G20425TQ", "G20706XG", "G22140GZ", "G22310AV", "G22572EH", "G22769FQ", "G23505EP", "G23863VK", "G24084IV", "G25418HZ", "G25520XG", "G26330YA", "G26915XM", "G27058EU", "G27126ED", "G27947YN", "G28681TP", "G29545VG", "G31028YV", "G31852PQ", "G31916IQ", "G31986NC", "G32926LW", "G34989PA", "G35541EV", "G36131WL", "G36191CD", "G37399XV", "G37692EO", "G37818NZ", "G37868ZX", "G40574BA", "G40834TG", "G40926MX", "G41247ZX", "G42358LZ", "G43223CG", "G43769HG", "G44753VC", "G45395BF", "G45495MK", "G45504EY", "G46503DX", "G46524LG", "G46691LC", "G46902YN", "G47518TP", "G47737VJ", "G48414YA", "G49642SA", "G49906RN", "G49955PK", "G50045TK", "G50143PC", "G50210FA", "G51640FO", "G51653BI", "G52527GH", "G53075ES", "G56518TU", "G57317CE", "G57776ZS", "G57776ZU", "G57818FI", "G58087IP", "G58954YZ", "G59536GA", "G59626AS", "G60033FS", "G62765YT", "G63980BQ", "G64275UO", "G65184UU", "G66760KM", "G70232NH", "G70619PT", "G70888PK", "G71146HJ", "G72398FA", "G72747WU", "G72790NZ", "G74430RZ", "G75798PH", "G75983OB", "G76868JS", "G77459ND", "G77669RF", "G78059CC", "G78787DI", "G78790NZ", "G79666IR", "G80075MS", "G80223IX", "G80735OA", "G80920RR", "G81124ET", "G81295CK", "G81637OR", "G82830MN", "G83460ZZ", "G83646BJ", "G84225JN", "G84452RH", "G84467IZ", "G85269DF", "G85282JO", "G85554PZ", "G86182NS", "G86880BF", "G87123QX", "G87418CY", "G88374WZ", "G89098OM", "G89877QI", "G90659AW", "G91473PK", "G92050GC", "G92551JA", "G94470IW", "G94665LC", "G95865ZB", "G95977AE", "G98129XB", "G98611JV", "G98736SM", "G99668VU", "G99679NM", "G00273SJ", "G01485JJ", "G02528FI", "G03644CB", "G05049YU", "G05933EN", "G07799LX", "G08146BT", "G10488MI", "G14972EH", "G15169WU", "G17208MA", "G20528HD", "G23719VF", "G27915IV", "G28541PG", "G30248BL", "G30740WO", "G31118FR", "G33416PL", "G36379GD", "G37412TK", "G37995HC", "G41071NU", "G41840AI", "G42124LM", "G43669FQ", "G43734MM", "G47644PP", "G47702MW", "G47950XN", "G49755GI", "G54010QB", "G59297UK", "G59324HL", "G59937CP", "G60923RB", "G61256FT", "G63041LO", "G68735SN", "G69521XL", "G70223PD", "G70441OD", "G72291OX", "G72787SB", "G73430PD", "G73968GN", "G74608QW", "G76295SF", "G77338BR", "G77547TA", "G80479JV", "G85144OK", "G85740DB", "G86500WE", "G87389XI", "G87661QW", "G89045VA", "G90382BL", "G91636VS", "G92135MA", "G94917XT", "G95177YH", "G96091TT", "G00031MO", "G00395TQ", "G05724UK", "G06110VR", "G07483YN", "G07995VK", "G08939IS", "G10256JP", "G11041DA", "G11460AB", "G12398HZ", "G14047PA", "G14669DU", "G19958IL", "G22768VO", "G23453IV", "G23616ZX", "G26864OJ", "G27383GK", "G28916LJ", "G29880MM", "G29931IJ", "G30159WR", "G31685JQ", "G33241WC", "G34499SX", "G36004BS", "G36836GD", "G39188ZX", "G40702WU", "G43702IX", "G45560HM", "G45889JQ", "G47832TO", "G49108TO", "G55220VL", "G55383ZG", "G56749GV", "G57173NZ", "G60145BJ", "G60230HH", "G61751GZ", "G64162JC", "G64527OM", "G65562ZE", "G66665YI", "G66951WQ", "G68164MW", "G68668TB", "G68796US", "G69411IG", "G70101JE", "G72797UR", "G72956NR", "G74722FL", "G74724QE", "G76675AB", "G77252PU", "G80966KZ", "G82348BZ", "G83161QT", "G91365ZQ", "G91704UR", "G93775KQ", "G94239KE", "G94854LT", "G96921ZU", "G97674NY", "G97947UQ" ], "uniprot_id": "P02787" }, "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "medium", "disease": "Coagulopathy", "glycan_involvement": "N-glycosylation modulates clot formation and stability.", "mechanism": "Elevated fibrinogen is associated with hypercoagulability in COVID-19.", "protein": "Fibrinogen", "protein_enriched": { "function": "Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in ", "gene_name": "FGA", "glycan_count": 20, "glycosylation_sites_count": 4, "glytoucan_ids": [ "G57321FI", "G73004SD", "G43417UB", "G29068FM", "G17015OC", "G00912UN", "G25418HZ", "G39619TI", "G45395BF", "G59626AS", "G62765YT", "G78790NZ", "G06356OH", "G36191CD", "G48414YA", "G49108TO", "G50045TK", "G75850OP", "G84467IZ", "G91365ZQ" ], "uniprot_id": "P02671" }, "relationship_type": "biomarker", "source_pmcid": "PMC9984757" }, { "confidence": "high", "disease": "colonic diseases", "glycan_involvement": "Increased sialylation of mucins due to altered glycosyltransferase expression.", "mechanism": "Missense mutation in FCGBP impairs mucus barrier by altering glycosylation of MUC2, increasing penetrability.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9991123" }, { "confidence": "medium", "disease": "inflammatory bowel disease", "glycan_involvement": "Changes in glycosylation, especially sialylation, affect barrier function.", "mechanism": "Altered glycosylation of MUC2 is associated with impaired mucus barrier in IBD.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991123" }, { "confidence": "medium", "disease": "colon cancer", "glycan_involvement": "Increased sialylation is a hallmark of disease.", "mechanism": "Altered glycosylation of MUC2 is observed in colon cancer, affecting mucus barrier integrity.", "protein": "MUC2", "protein_enriched": { "function": "Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Co I is the catalytic subun", "gene_name": "ctaD", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P98059" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991123" }, { "confidence": "medium", "disease": "inflammatory bowel disease", "glycan_involvement": "Alters glycosylation of MUC2, increasing sialylated glycans.", "mechanism": "Mutation in FCGBP disrupts mucus barrier, predisposing to inflammation.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9991123" }, { "confidence": "medium", "disease": "colon cancer", "glycan_involvement": "Increased sialylation of mucins.", "mechanism": "Impaired FCGBP function leads to mucus barrier defects, a risk factor for colon cancer.", "protein": "FCGBP", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "causal", "source_pmcid": "PMC9991123" }, { "confidence": "high", "disease": "Autoimmune Polyendocrine Syndrome Type 1 (APS-1)", "glycan_involvement": "IgG is a glycoprotein; glycosylation modulates immune effector functions.", "mechanism": "Elevated IgG reflects ongoing autoimmune activity in APS-1.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9991173" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "IgG glycosylation affects antibody-mediated inflammation.", "mechanism": "Elevated IgG is associated with autoimmune hepatitis.", "protein": "IgG", "protein_enriched": { "function": "", "gene_name": null, "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": null }, "relationship_type": "biomarker", "source_pmcid": "PMC9991173" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "ANA are glycoproteins; glycosylation may affect antigen recognition.", "mechanism": "Positive ANA is a marker for autoimmune hepatitis.", "protein": "ANA", "relationship_type": "biomarker", "source_pmcid": "PMC9991173" }, { "confidence": "medium", "disease": "Autoimmune hepatitis", "glycan_involvement": "ASMA are glycoproteins; glycosylation may affect immune complex formation.", "mechanism": "Positive ASMA is a marker for autoimmune hepatitis.", "protein": "ASMA", "relationship_type": "biomarker", "source_pmcid": "PMC9991173" }, { "confidence": "high", "disease": "Autoimmune Polyendocrine Syndrome Type 1 (APS-1)", "glycan_involvement": "AIRE is not a glycoprotein; no direct glycan involvement.", "mechanism": "AIRE mutations disrupt central tolerance, causing APS-1.", "protein": "AIRE", "relationship_type": "causal", "source_pmcid": "PMC9991173" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "Not specified in article", "mechanism": "AST is used in the FAST score to identify NASH with fibrosis", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9991199" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Not specified in article", "mechanism": "AST levels contribute to non-invasive scoring of liver fibrosis (FAST score)", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9991199" }, { "confidence": "medium", "disease": "Nonalcoholic steatohepatitis (NASH)", "glycan_involvement": "AST is a glycoprotein; glycosylation may affect its stability and serum levels", "mechanism": "AST is used in the FAST score to identify NASH with fibrosis", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9991260" }, { "confidence": "medium", "disease": "Liver fibrosis", "glycan_involvement": "Glycosylation may influence AST clearance and detection", "mechanism": "AST levels contribute to non-invasive fibrosis assessment (FAST score)", "protein": "aspartate aminotransferase (AST)", "relationship_type": "biomarker", "source_pmcid": "PMC9991260" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Altered O-glycan structures (glycan 'fingerprinting') detected in UC, suggesting disease-associated glycosylation changes.", "mechanism": "Differential O-glycosylation profile of MUC2 observed in UC patients compared to healthy controls.", "protein": "Mucin-2 (MUC2)", "relationship_type": "biomarker", "source_pmcid": "PMC9991287" }, { "confidence": "high", "disease": "Inflammatory Bowel Disease (IBD)", "glycan_involvement": "O-glycosylation of MUC2 is essential for barrier function and microbial interactions.", "mechanism": "MUC2 forms a barrier segregating inflammatory microbes from colon tissue, maintaining host-microbe homeostasis.", "protein": "Mucin-2 (MUC2)", "relationship_type": "protective", "source_pmcid": "PMC9991287" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Changes in O-glycan composition (e.g., sialylation, fucosylation) may impair barrier properties.", "mechanism": "Potential MUC2 dysfunction (altered glycosylation) may contribute to barrier defects and disease pathogenesis.", "protein": "Mucin-2 (MUC2)", "relationship_type": "causal", "source_pmcid": "PMC9991287" }, { "confidence": "high", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Reduced O-glycosylation of Muc2 compromises mucus structure and function.", "mechanism": "Impaired Muc2 glycosylation leads to a thinner mucus barrier, facilitating E. coli pathobiont adherence and colitis.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "causal", "source_pmcid": "PMC9991288" }, { "confidence": "high", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Core 1 O-glycans are essential for proper Muc2 glycosylation.", "mechanism": "Genetic deficiency in C1galt1 reduces core 1 O-glycans, impairing Muc2 glycosylation and mucus barrier, increasing susceptibility to colitis.", "protein": "Core 1 O-glycans (C1galt1)", "relationship_type": "causal", "source_pmcid": "PMC9991288" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "O-glycosylation maintains mucus barrier integrity.", "mechanism": "Intact, glycosylated Muc2 forms a mucus barrier preventing E. coli pathobiont contact with the mucosa.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "protective", "source_pmcid": "PMC9991288" }, { "confidence": "high", "disease": "Colitis", "glycan_involvement": "Core 1 O-glycans required for Muc2 function.", "mechanism": "Loss of C1galt1 in IECs leads to reduced Muc2 glycosylation and increased colitis upon E. coli pathobiont exposure.", "protein": "Core 1 O-glycans (C1galt1)", "relationship_type": "causal", "source_pmcid": "PMC9991288" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Altered O-glycosylation status detectable in UC patients.", "mechanism": "Impaired Muc2 glycosylation and mucus thinning are features of UC.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991288" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "Therapies targeting O-glycosylation or mucus production.", "mechanism": "Restoring Muc2 glycosylation or mucus thickness may reduce colitis susceptibility.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9991288" }, { "confidence": "high", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Diet affects O-glycosylation and mucus barrier.", "mechanism": "Diet-induced mucus thinning (fiber-free diet) reduces Muc2 glycosylation, increasing UC pathobiont adherence and colitis.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "causal", "source_pmcid": "PMC9991288" }, { "confidence": "medium", "disease": "Colitis", "glycan_involvement": "SCFA production is linked to mucus glycosylation and barrier function.", "mechanism": "Exogenous SCFA (tributyrin) supplementation reduces E. coli pathobiont infection and colitis.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9991288" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Mucin O-glycans serve as nutrients for pathobionts.", "mechanism": "E. coli pathobionts utilize mucin-derived sugars for growth, promoting colitis when mucus is impaired.", "protein": "Mucin 2 (Muc2)", "protein_enriched": { "function": "Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex whi", "gene_name": "Rpl13a", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P35427" }, "relationship_type": "causal", "source_pmcid": "PMC9991288" }, { "confidence": "medium", "disease": "Ulcerative Colitis (UC)", "glycan_involvement": "Loss of core 1 O-glycans detectable in susceptible individuals.", "mechanism": "Genetic deficiency in C1galt1 correlates with increased UC susceptibility.", "protein": "Core 1 O-glycans (C1galt1)", "relationship_type": "biomarker", "source_pmcid": "PMC9991288" }, { "confidence": "high", "disease": "Cystic fibrosis related liver disease (CFLD)", "glycan_involvement": "GGT is a glycoprotein; glycosylation affects its stability and secretion.", "mechanism": "Elevated GGT reflects cholestasis and hepatobiliary injury in CFLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "high", "disease": "Cystic fibrosis related liver disease (CFLD)", "glycan_involvement": "ALP is a glycoprotein; glycosylation modulates its activity and serum half-life.", "mechanism": "Elevated ALP indicates biliary tract involvement in CFLD.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). 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Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with ", "gene_name": "GPT", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "P24298" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation affects GGT's serum detection.", "mechanism": "GGT elevation can indicate hepatic steatosis in CF patients.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "medium", "disease": "Hepatic steatosis", "glycan_involvement": "Glycosylation modulates ALP's function.", "mechanism": "ALP may be elevated in hepatic steatosis, reflecting biliary involvement.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation affects GGT's serum levels.", "mechanism": "Elevated GGT may be associated with portal hypertension in CFLD.", "protein": "Gamma-glutamyl transferase (GGT)", "protein_enriched": { "function": "Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling", "gene_name": "Muc13", "glycan_count": 0, "glycosylation_sites_count": 3, "glytoucan_ids": [], "uniprot_id": "P19467" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "low", "disease": "Portal hypertension", "glycan_involvement": "Glycosylation modulates ALP's activity.", "mechanism": "ALP elevation may reflect biliary tract changes in portal hypertension.", "protein": "Alkaline phosphatase (ALP)", "protein_enriched": { "function": "Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has br", "gene_name": "ALPL", "glycan_count": 38, "glycosylation_sites_count": 5, "glytoucan_ids": [ "G02815KT", "G48414YA", "G62765YT", "G80920RR", "G05962QB", "G13131HA", "G70441OD", "G80479JV", "G83646BJ", "G85282JO", "G49108TO", "G07246CJ", "G08918WF", "G10486CT", "G10819WX", "G27058EU", "G27947YN", "G40926MX", "G41071NU", "G43223CG", "G49906RN", "G59626AS", "G65184UU", "G68490OW", "G79666IR", "G80075MS", "G86880BF", "G87661QW", "G90659AW", "G92135MA", "G98611JV", "G11629QQ", "G12959FT", "G15169WU", "G22310AV", "G55412XP", "G81263BG", "G84452RH" ], "uniprot_id": "P05186" }, "relationship_type": "biomarker", "source_pmcid": "PMC9991356" }, { "confidence": "medium", "disease": "Severe acute hepatitis of unknown origin (SAH)", "glycan_involvement": "Hexon protein is a glycoprotein involved in viral entry and immune evasion.", "mechanism": "Adenoviral DNA detected in blood, stool, and nasopharyngeal swab of affected child; unclear if causative.", "protein": "Human adenovirus hexon protein", "relationship_type": "biomarker", "source_pmcid": "PMC9991367" }, { "confidence": "medium", "disease": "Paediatric acute liver failure (PALF)", "glycan_involvement": "Glycosylation of hexon protein may affect host immune recognition.", "mechanism": "Presence of adenoviral DNA temporally associated with rapid progression to PALF.", "protein": "Human adenovirus hexon protein", "relationship_type": "biomarker", "source_pmcid": "PMC9991367" }, { "confidence": "high", "disease": "Chronic Antibody-Mediated Rejection (CABMR)", "glycan_involvement": "IL-6 is a glycoprotein; glycosylation may affect its stability and receptor interactions (not directly discussed in article).", "mechanism": "IL-6 is upregulated in fibroblasts and serum of CABMR patients, driving chronic inflammation and rejection via the IL-6 amplifier loop (IL-6+IL-17) and activating NF\u03baB/STAT3 signaling.", "protein": "Interleukin-6 (IL-6)", "protein_enriched": { "function": "Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. 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Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the in", "gene_name": "IL6", "glycan_count": 0, "glycosylation_sites_count": 1, "glytoucan_ids": [], "uniprot_id": "P05231" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9997681" }, { "confidence": "high", "disease": "Chronic Antibody-Mediated Rejection (CABMR)", "glycan_involvement": "Not specified.", "mechanism": "Inhibition of IL-17 with anti-IL-17 reduces markers of tissue injury and rejection.", "protein": "IL-17", "protein_enriched": { "function": "", "gene_name": "", "glycan_count": 0, "glycosylation_sites_count": 0, "glytoucan_ids": [], "uniprot_id": "Q8NAC6" }, "relationship_type": "therapeutic_target", "source_pmcid": "PMC9997681" } ], "total_relationships": 39319, "version": "1.0" }